204 results on '"Shiramizu, B"'
Search Results
52. HIV PROVIRAL DNA AND MONOCYTE CHEMOATTRACTANT PROTEIN 1 IN CEREBROSPINAL FLUID FROM HIV-1-INFECTED CHILDREN.
- Author
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Lau, E., Tamamoto, A., Uniatowski, J., Troelstrup, D., Shikuma, C., and Shiramizu, B.
- Published
- 2006
- Full Text
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53. Impact of antiretroviral therapy intensification with C-C motif chemokine receptor 5 antagonist maraviroc on HIV-associated neurocognitive impairment.
- Author
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Shikuma CM, Wojna V, De Gruttola V, Siriwardhana C, Souza SA, Rodriguez-Benitez RJ, Turner EH, Kallianpur K, Bolzenius J, Chow D, Matos M, Shiramizu B, Clements DM, Premeaux TA, Ndhlovu LC, and Paul R
- Subjects
- Humans, Maraviroc, Cyclohexanes, Triazoles therapeutic use, Antiretroviral Therapy, Highly Active, HIV Infections complications, HIV Infections drug therapy
- Abstract
Objectives: Chemokine receptor CCR5 is the principal co-receptor for entry of M-tropic HIV virus into immune cells. It is expressed in the central nervous system and may contribute to neuro-inflammation. The CCR5 antagonist maraviroc (MVC) has been suggested to improve HIV-associated neurocognitive impairment (NCI)., Design: A double-blind, placebo-controlled, 48-week, randomized study of MVC vs. placebo in people with HIV (PWH) on stable antiretroviral therapy (ART) for more than one year in Hawaii and Puerto Rico with plasma HIV RNA less than 50 copies/ml and at least mild NCI defined as an overall or domain-specific neuropsychological z (NPZ) score less than -0.5., Methods: Study participants were randomized 2 : 1 to intensification of ART with MVC vs. placebo. The primary endpoint was change in global and domain-specific NPZ modeled from study entry to week 48. Covariate adjusted treatment comparisons of average changes in cognitive outcome were performed using winsorized NPZ data. Monocyte subset frequencies and chemokine expression as well as plasma biomarker levels were assessed., Results: Forty-nine participants were enrolled with 32 individuals randomized to MVC intensification and 17 to placebo. At baseline, worse NPZ scores were seen in the MVC arm. Comparison of 48-week NPZ change by arm revealed no differences except for a modest improvement in the Learning and Memory domain in the MVC arm, which did not survive multiplicity correction. No significant changes between arms were seen in immunologic parameters., Conclusion: This randomized controlled study found no definitive evidence in favor of MVC intensification among PWH with mild cognitive difficulties., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2023
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54. Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV.
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Park J, Dean LS, Heckl J, Gangcuangco LM, Pedro TK, Tallquist MD, Seto TB, Shiramizu B, Chow DC, and Shikuma CM
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- Humans, Histones, Neutrophils, Aging, Granulocytes, HIV Infections
- Abstract
While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutrophil dysregulation and the pathological role of NETs in HIV, we examined expressions of NET-associated markers [cell-free DNA (cfDNA) and citrullinated histone H3 (CitH3)] in the plasmas from a cohort of the Hawaii Aging with HIV-cardiovascular and HIV-seronegative (HIV-) individuals. In a subset of participants, circulating low-density granulocyte (LDG) levels and their maturation and activation status were analyzed via flow cytometry. We demonstrated higher plasma levels of CitH3 in PLWH compared to HIV- individuals. LDGs from PLWH had heightened CD66b, but reduced CD16 expression. The percentages and counts of CD10
+ LDGs were significantly decreased in PLWH. In addition, the CD16Lo LDG subsets were enriched in PLWH, compared to HIV- group, indicating that immature LDGs are increased in PLWH. Moreover, LDGs from PLWH exhibited significantly higher NET forming capacity. In summary, our study presents evidence that LDGs from PLWH on ART display an immature and altered phenotype with increased NET formation. Among PLWH, plasma NET levels as well as LDG parameters correlated with blood markers for inflammation and coagulation, suggesting that neutrophil activation and NETs may exert proinflammatory and coagulation effects. Our data provide insights into the pathologic role of LDGs at least in part mediated through NET formation in PLWH., (© 2023. Springer Nature Limited.)- Published
- 2023
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55. A dose substitution of anthracycline intensity with dose-dense rituximab in children and adolescents with good-risk mature B-cell lymphoma.
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Goldman S, Barth M, Shiramizu B, Shi Q, Hochberg J, Klejmont L, Harrison L, Basso J, Chu Y, Islam H, Gerard P, Agsalda-Garcia M, Shieh T, Oesterheld J, Heym K, Kirov I, Drachtman R, Harker-Murray P, Perkins S, Miles RR, and Cairo M
- Subjects
- Adolescent, Adult, Anthracyclines administration & dosage, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Lymphoma, B-Cell pathology, Male, Prognosis, Rituximab administration & dosage, Survival Rate, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, B-Cell drug therapy
- Published
- 2021
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56. Super-multiplex imaging of cellular dynamics and heterogeneity by integrated stimulated Raman and fluorescence microscopy.
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Shou J, Oda R, Hu F, Karasawa K, Nuriya M, Yasui M, Shiramizu B, Min W, and Ozeki Y
- Abstract
Observing multiple molecular species simultaneously with high spatiotemporal resolution is crucial for comprehensive understanding of complex, dynamic, and heterogeneous biological systems. The recently reported super-multiplex optical imaging breaks the "color barrier" of fluorescence to achieve multiplexing number over six in living systems, while its temporal resolution is limited to several minutes mainly by slow color tuning. Herein, we report integrated stimulated Raman and fluorescence microscopy with simultaneous multimodal color tunability at high speed, enabling super-multiplex imaging covering diverse molecular contrasts with temporal resolution of seconds. We highlight this technique by demonstrating super-multiplex time-lapse imaging and image-based cytometry of live cells to investigate the dynamics and cellular heterogeneity of eight intracellular components simultaneously. Our technique provides a powerful tool to elucidate spatiotemporal organization and interactions in biological systems., Competing Interests: The authors declare no competing interests., (© 2021.)
- Published
- 2021
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57. IDeA States Pediatric Clinical Trials Network for Underserved and Rural Communities.
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Annett RD, Chervinskiy S, Chun TH, Cowan K, Foster K, Goodrich N, Hirschfeld M, Hsia DS, Jarvis JD, Kulbeth K, Madden C, Nesmith C, Raissy H, Ross J, Saul JP, Shiramizu B, Smith P, Sullivan JE, Tucker L, and Atz AM
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- Capacity Building, Child Health, Clinical Trials as Topic economics, Education, Continuing, Humans, Research Support as Topic economics, United States, Clinical Trials as Topic organization & administration, Medically Underserved Area, Pediatrics, Research Support as Topic organization & administration, Rural Population
- Abstract
The National Institutes of Health's Environmental Influences on Child Health Outcomes (ECHO) program aims to study high-priority and high-impact pediatric conditions. This broad-based health initiative is unique in the National Institutes of Health research portfolio and involves 2 research components: (1) a large group of established centers with pediatric cohorts combining data to support longitudinal studies (ECHO cohorts) and (2) pediatric trials program for institutions within Institutional Development Awards states, known as the ECHO Institutional Development Awards States Pediatric Clinical Trials Network (ISPCTN). In the current presentation, we provide a broad overview of the ISPCTN and, particularly, its importance in enhancing clinical trials capabilities of pediatrician scientists through the support of research infrastructure, while at the same time implementing clinical trials that inform future health care for children. The ISPCTN research mission is aligned with the health priority conditions emphasized in the ECHO program, with a commitment to bringing state-of-the-science trials to children residing in underserved and rural communities. ISPCTN site infrastructure is critical to successful trial implementation and includes research training for pediatric faculty and coordinators. Network sites exist in settings that have historically had limited National Institutes of Health funding success and lacked pediatric research infrastructure, with the initial funding directed to considerable efforts in professional development, implementation of regulatory procedures, and engagement of communities and families. The Network has made considerable headway with these objectives, opening two large research studies during its initial 18 months as well as producing findings that serve as markers of success that will optimize sustainability., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)
- Published
- 2020
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58. Frailty Is Associated With Insulin Resistance in Chronic Human Immunodeficiency Virus Infection.
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Chow DC, Bernas MA, Gangcuangco LM, Huynh J, Kohorn LB, Kallianpur KJ, Souza SA, Shiramizu B, Ndhlovu LC, and Shikuma CM
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- Adult, Aging, HIV, Humans, Risk Factors, Bone Diseases, Cardiovascular Diseases, Diabetes Mellitus, Frailty, HIV Infections complications, Insulin Resistance
- Published
- 2020
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59. Medical School Location and Sex Affect the In-State Retention of Pediatric Residency Program Graduates in Hawai'i.
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Kurahara D, Hamamura FD, Ifuku C, Chen JJ, Liu CA, Seamon EM, Miwa CS, Maestas B, Oba R, Patel SJ, and Shiramizu B
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- Adult, Female, Hawaii, Humans, Internship and Residency statistics & numerical data, Male, Odds Ratio, Pediatrics statistics & numerical data, Physicians psychology, Physicians statistics & numerical data, Professional Practice Location statistics & numerical data, Schools, Medical organization & administration, Schools, Medical statistics & numerical data, Geographic Mapping, Internship and Residency standards, Pediatrics education, Sex Factors
- Abstract
The objective of this study was to assess the impact of medical school, sex, career choice, and location of practice of one pediatric residency program on physician workforce. This is a retrospective study of all categorical pediatric graduates of a residency program located in Honolulu, Hawai'i from 1968 to 2015. Information on medical school training, sex, career choice (general pediatrics or specialty), and location of practice were studied by examining data into five 10-year graduation periods. The program graduated 319 residents over nearly a 50-year timespan. Of these, 181 (56.7%) residents remained in Hawai'i to practice (adjusted odds ratio [OR] = 7.46, 95% confidence interval [CI]: 3.61-15.43). There were 125 (39.1%) graduates who relocated to the continental US with the majority moving to the West (55.2%), while other graduates moved to the South, Midwest, and Northeast (25.6%, 13.6%, and 5.6%, respectively). The remaining 13 (4.1%) graduates moved internationally. Female residents steadily increased over time ( P < .001), with females significantly choosing general pediatrics (OR = 3.05, 95% CI: 1.91-4.89). In the time periods with the highest percentage of University of Hawai'i medical school graduates, there was an increased percentage of graduates staying in Hawai'i. This study examined the regional and national impact of a small residency program. The results indicated that trends in gender and the impact of medical school location were important in establishing a pediatrician workforce for local communities. Support of both medical school and residency education should be considered when assessing future workforce needs., (©Copyright 2020 by University Health Partners of Hawai‘i (UHP Hawai‘i).)
- Published
- 2020
60. Relationship between Circulating Inflammatory Monocytes and Cardiovascular Disease Measures of Carotid Intimal Thickness.
- Author
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SahBandar IN, Ndhlovu LC, Saiki K, Kohorn LB, Peterson MM, D'Antoni ML, Shiramizu B, Shikuma CM, and Chow DC
- Subjects
- Cardiovascular Diseases blood, Cardiovascular Diseases immunology, Cardiovascular Diseases physiopathology, Carotid Intima-Media Thickness, Cross-Sectional Studies, Disease Progression, Female, Heart Disease Risk Factors, Humans, Immunity, Innate, Leukocyte Count, Male, Middle Aged, Predictive Value of Tests, Prognosis, Atherosclerosis blood, Atherosclerosis diagnosis, Carotid Arteries diagnostic imaging, Leukocytes, Mononuclear immunology
- Abstract
Aims: Cardiovascular disease (CVD) remains the leading cause of death worldwide despite improvements in the treatment of atherosclerosis, an inflammatory disease and major underlying cause of CVD. Monocytes, an innate immune cell type, are linked to CVD progression; however, given their heterogeneity, the association between distinct monocyte subsets and increased risk of CVD remains unclear. This study investigated the association between peripheral monocyte subpopulation numbers and carotid intima-media thickness (cIMT), a sensitive measure of CVD risk, in a cohort of adults recruited from the general population., Methods: We used clinical data and peripheral blood mononuclear cell (PBMC) specimens from 67 individuals. cIMT was measured by high-resolution, B-mode, ultrasound images of the right carotid artery. PBMCs were stained with conjugated monoclonal antibodies to define monocyte subpopulations based on CD14 and CD16 co-expressions into classical (CD14
++ CD16- ), intermediate/inflammatory (CD14++ CD16+ ), and non-classical/patrolling (CD14low/+ CD16++ ) monocytes., Results: We found a higher intermediate monocyte count was significantly correlated with increased right common carotid artery (RCCA) and right carotid bifurcation (RBIF) intima-media thickness (IMT) (p=0.004 and 0.006,respectively), even after adjusting for CVD-associated clinical data (p=0.006 and 0.004, respectively)., Conclusion: Our study demonstrated a strong correlation between inflammatory monocyte counts and cIMT. These results suggest that, in the general population, there is a relationship between intermediate monocyte expansion and elevated predictors for CVD risk, and intermediate monocytes may be involved in the development of atherosclerosis and metabolic diseases. Strategies targeting inflammatory monocytes may be needed to slow CVD progression.- Published
- 2020
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61. Hawai'i IDeA Center for Pediatric and Adolescent Clinical Trials.
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Shiramizu B, Okihiro MM, Kosut JS, Wu BH, Akshatha A, Neal C Jr, Amiotte A, Siu A, Lee MJ, Balaraman V, and Easa D
- Subjects
- Hawaii, Humans, Pediatrics methods, Awards and Prizes, Clinical Trials as Topic standards, Program Development standards
- Abstract
As one of 17 clinical sites of the Environmental influences on Child Health Outcomes (ECHO) IDeA States Pediatric Clinical Trials Network (ISPCTN), the Hawai'i IDeA Center for Pediatric and Adolescent Clinical Trials (HIPACT) was established in 2016 to participate in community-valued and scientifically-valid multi-center pediatric clinical trials to improve health and well-being of diverse multi-ethnic populations of Hawai'i. Hawai'i is home to large populations of diverse rural and underserved populations, including indigenous Hawaiian communities and immigrant populations of Pacific Islanders and Asians. Many of these communities experience significant health disparities, made worse by their geographic isolation and many socio-economic factors. In addition to providing opportunities for children and their families to participate in clinical trials, HIPACT's goal is to provide opportunities for junior faculty of the John A. Burns School of Medicine (JABSOM), University of Hawai'i at Manoa, to acquire knowledge about and to develop skills in clinical trials. HIPACT's partners include the Hawai'i Pacific Health with Kapi'olani Medical Center for Women and Children, and Waianae Coast Comprehensive Health Center. HIPACT builds on the experiences gained through partnerships with the Mountain West IDeA Clinical and Translational Research-Infrastructure Network, and Research Centers in Minority Institutions Translational Research Network. Apart from participating in ECHO ISPCTN-sponsored studies, HIPACT junior faculty serve as committee members, Working Group leaders, Protocol Study Principal Investigators (PI) and site study PIs with ECHO ISPCTN. Through participation in ECHO ISPCTN, HIPACT has successfully increased the number of pediatric and maternal-fetal medicine faculty involved in the conduct of clinical trials., Competing Interests: None of the authors identified any conflicts of interest., (©Copyright 2020 by University Health Partners of Hawai‘i (UHP Hawai‘i).)
- Published
- 2020
62. Pre-exposure Prophylaxis Therapy and the Blood-Brain Barrier: Is PrEP Neuroprotective?
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Kettlewell J, Barney M, Oda R, Agsalda-Garcia M, Siriwardhana C, and Shiramizu B
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- Adult, Blood-Brain Barrier metabolism, Humans, Monocytes drug effects, Monocytes metabolism, Anti-HIV Agents administration & dosage, Blood-Brain Barrier drug effects, Emtricitabine administration & dosage, Neuroprotective Agents administration & dosage, Pre-Exposure Prophylaxis methods, Tenofovir administration & dosage
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- 2020
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63. Raman-Enhanced Spectroscopy (RESpect) Probe for Childhood Non-Hodgkin Lymphoma.
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Agsalda-Garcia M, Shieh T, Souza R, Kamada N, Loi N, Oda R, Acosta-Maeda T, Choi SY, Lim E, Misra A, and Shiramizu B
- Abstract
Raman-enhanced spectroscopy (RESpect) probe, which enhances Raman spectroscopy technology through a portable fiber-optic device, characterizes tissues and cells by identifying molecular chemical composition showing distinct differences/similarities for potential tumor markers or diagnosis. In a feasibility study with the ultimate objective to translate the technology to the clinic, a panel of pediatric non-Hodgkin lymphoma tissues and non-malignant specimens had RS analyses compared between standard Raman spectroscopy microscope instrument and RESpect probe. Cryopreserved tissues were mounted on front-coated aluminum mirror slides and analyzed by standard Raman spectroscopy and RESpect probe. Principal Component Analysis revealed similarities between non-Hodgkin lymphoma subtypes but not follicular hyperplasia. Standard Raman spectroscopy and RESpect probe fingerprint comparisons demonstrated comparable primary peaks. Raman spectroscopic fingerprints and peaks of pediatric non-Hodgkin lymphoma subtypes and follicular hyperplasia provided novel avenues to pursue diagnostic approaches and identify potential new therapeutic targets. The information could inform new insights into molecular cellular pathogenesis. Translating Raman spectroscopy technology by using the RESpect probe as a potential point-of-care screening instrument has the potential to change the paradigm of screening for cancer as an initial step to determine when a definitive tissue biopsy would be necessary., Competing Interests: 7.Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2020
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64. S100B and its association with HIV-associated neurocognitive disorders.
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Limpruttidham N, Mitchell BI, Kallianpur KJ, Nakamoto BK, Souza SA, Shiramizu B, Ndhlovu LC, Chow DC, and Shikuma CM
- Subjects
- Biomarkers, Humans, Neurocognitive Disorders, S100 Calcium Binding Protein beta Subunit, Uganda, HIV Infections
- Published
- 2019
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65. Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals.
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Premeaux TA, D'Antoni ML, Abdel-Mohsen M, Pillai SK, Kallianpur KJ, Nakamoto BK, Agsalda-Garcia M, Shiramizu B, Shikuma CM, Gisslén M, Price RW, Valcour V, and Ndhlovu LC
- Subjects
- Adult, Age Factors, Anti-HIV Agents therapeutic use, Antigens, CD cerebrospinal fluid, Antigens, Differentiation, Myelomonocytic cerebrospinal fluid, Antiretroviral Therapy, Highly Active, Biomarkers cerebrospinal fluid, Case-Control Studies, Central Nervous System drug effects, Central Nervous System metabolism, Central Nervous System physiopathology, Cognition drug effects, Cognition physiology, Female, Galectins cerebrospinal fluid, HIV Infections cerebrospinal fluid, HIV Infections drug therapy, HIV Infections immunology, HIV-1 genetics, HIV-1 pathogenicity, Humans, Male, Middle Aged, Neopterin cerebrospinal fluid, Neuropsychological Tests, RNA, Viral cerebrospinal fluid, Viremia cerebrospinal fluid, Viremia drug therapy, Viremia immunology, Antigens, CD genetics, Antigens, Differentiation, Myelomonocytic genetics, Central Nervous System virology, Galectins genetics, HIV Infections virology, RNA, Viral genetics, Receptors, Cell Surface genetics, Viremia virology
- Abstract
We previously reported that galectin-9 (Gal-9), a soluble lectin with immunomodulatory properties, is elevated in plasma during HIV infection and induces HIV transcription. The link between Gal-9 and compromised neuronal function is becoming increasingly evident; however, the association with neuroHIV remains unknown. We measured Gal-9 levels by ELISA in cerebrospinal fluid (CSF) and plasma of 70 HIV-infected (HIV+) adults stratified by age (older > 40 years and younger < 40 years) either ART suppressed or with detectable CSF HIV RNA, including a subgroup with cognitive assessments, and 18 HIV uninfected (HIV-) controls. Gal-9 tissue expression was compared in necropsy brain specimens from HIV- and HIV+ donors using gene datasets and immunohistochemistry. Among older HIV+ adults, CSF Gal-9 was elevated in the ART suppressed and CSF viremic groups compared to controls, whereas in the younger group, Gal-9 levels were elevated only in the CSF viremic group (p < 0.05). CSF Gal-9 positively correlated with age in all groups (p < 0.05). CSF Gal-9 tracked with CSF HIV RNA irrespective of age (β = 0.33; p < 0.05). Higher CSF Gal-9 in the older viremic HIV+ group correlated with worse neuropsychological test performance scores independently of age and CSF HIV RNA (p < 0.05). Furthermore, CSF Gal-9 directly correlated with myeloid activation (CSF-soluble CD163 and neopterin) in both HIV+ older groups (p < 0.05). Among HIV+ necropsy specimens, Gal-9 expression was increased in select brain regions compared to controls (p < 0.05). Gal-9 may serve as a novel neuroimmuno-modulatory protein that is involved in driving cognitive deficits in those aging with HIV and may be valuable in tracking cognitive abnormalities.
- Published
- 2019
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66. Excellent outcomes in children and adolescents with CNS + Burkitt lymphoma or other mature B-NHL using only intrathecal and systemic chemoimmunotherapy: results from FAB/LMB96 and COG ANHL01P1.
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Frazer JK, Li KJ, Galardy PJ, Perkins SL, Auperin A, Anderson JR, Pinkerton R, Buxton A, Gross TG, Michon J, Leverger G, Weinstein HJ, Harrison L, Shiramizu B, Barth MJ, Goldman SC, Patte C, and Cairo MS
- Subjects
- Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy, Child, Female, Humans, Immunotherapy methods, Injections, Spinal, Kaplan-Meier Estimate, Male, Rituximab administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Central Nervous System Neoplasms drug therapy, Lymphoma, B-Cell drug therapy
- Published
- 2019
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67. Raman-Enhanced Spectroscopy Distinguishes Anal Squamous Intraepithelial Lesions in Human Immunodeficiency Virus-Serodiscordant Couples.
- Author
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Oda R, Agsalda-Garcia M, Loi N, Kamada N, Milne C, Killeen J, Choi SY, Lim E, Acosta-Maeda T, Misra A, and Shiramizu B
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- Adult, Anal Canal pathology, Anus Neoplasms diagnosis, Anus Neoplasms epidemiology, Biopsy, Female, HIV-1 immunology, Humans, Incidence, Male, Middle Aged, Anal Canal diagnostic imaging, Early Detection of Cancer methods, Family Characteristics, HIV Seropositivity pathology, Mass Screening methods, Precancerous Conditions diagnostic imaging, Sexual and Gender Minorities, Spectrum Analysis, Raman methods, Squamous Intraepithelial Lesions diagnostic imaging
- Abstract
HIV-positive individuals are at increased risk for precancerous anal squamous intraepithelial lesions (SILs). Anal cytology and digital rectal examination are performed as screening tools, but extensive training and appropriate instruments are required to follow up on an abnormal anal cytology. Thus, novel approaches to SIL evaluation could improve better health care follow-up by efficient and timely diagnosis to offer treatment options. Recently, Raman-enhanced spectroscopy (RESpect) has emerged as a potential new tool for early identification of SIL. RESpect is a noninvasive, label-free, laser-based technique that identifies molecular composition of tissues and cells. HIV-serodiscordant couples had anal biopsies obtained during high-resolution anoscopy. RESpect was performed on the specimens. Principal component analysis of the data identified differences between normal and abnormal tissue as well as HIV-positive and HIV-negative individuals of each couple even with similar pathologies. RESpect has the potential to change the paradigm of anal pathology diagnosis and could provide insight into different pathways leading to SIL in HIV-serodiscordant couples.
- Published
- 2019
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68. The Research Centers in Minority Institutions (RCMI) Translational Research Network: Building and Sustaining Capacity for Multi-Site Basic Biomedical, Clinical and Behavioral Research.
- Author
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Ofili EO, Tchounwou PB, Fernandez-Repollet E, Yanagihara R, Akintobi TH, Lee JE, Malouhi M, Garner ST Jr, Hayes TT, Baker AR, Dent AL 2nd, Abdelrahim M, Rollins L, Chang SP, Sy A, Hernandez BY, Bullard PL, Noel RJ Jr, Shiramizu B, Hedges JR, Berry MJ, Bond VC, Lima MF, Mokuau N, Kirken RA, Cruz-Correa M, Sarpong DF, Vadgama J, Yates C, Kahn SA, Soliman KF, Perry G, Pezzano M, Luciano CA, Barnett ME, Oyekan A, Kumar D, and Norris KC
- Subjects
- Cultural Diversity, Ethnicity education, Ethnicity statistics & numerical data, Health Status Disparities, Humans, Research Personnel, Research Support as Topic, United States, Workforce, Behavioral Research methods, Behavioral Research organization & administration, Biomedical Research methods, Biomedical Research organization & administration, Minority Groups education, Minority Groups statistics & numerical data, Minority Health education, Minority Health ethnology, Translational Research, Biomedical methods, Translational Research, Biomedical organization & administration
- Abstract
The Research Centers in Minority Institutions (RCMI) program was established by the US Congress to support the development of biomedical research infrastructure at minority-serving institutions granting doctoral degrees in the health professions or in a health-related science. RCMI institutions also conduct research on diseases that disproportionately affect racial and ethnic minorities (ie, African Americans/Blacks, American Indians and Alaska Natives, Hispanics, Native Hawaiians and Other Pacific Islanders), those of low socioeconomic status, and rural persons. Quantitative metrics, including the numbers of doctoral science degrees granted to underrepresented students, NIH peer-reviewed research funding, peer-reviewed publications, and numbers of racial and ethnic minorities participating in sponsored research, demonstrate that RCMI grantee institutions have made substantial progress toward the intent of the Congressional legislation, as well as the NIH/NIMHD-linked goals of addressing workforce diversity and health disparities. Despite this progress, nationally, many challenges remain, including persistent disparities in research and career development awards to minority investigators. The continuing underrepresentation of minority investigators in NIH-sponsored research across multiple disease areas is of concern, in the face of unrelenting national health inequities. With the collaborative network support by the RCMI Translational Research Network (RTRN), the RCMI community is uniquely positioned to address these challenges through its community engagement and strategic partnerships with non-RCMI institutions. Funding agencies can play an important role by incentivizing such collaborations, and incorporating metrics for research funding that address underrepresented populations, workforce diversity and health equity., Competing Interests: Competing Interests: None declared.
- Published
- 2019
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69. Red blood cell distribution width as an easily measurable biomarker of persistent inflammation and T cell dysregulation in antiretrovirally treated HIV-infected adults.
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Zhang Z, Chew GM, Shikuma CM, Gangcuangco LMA, Souza SA, Shiramizu B, Nakamoto BK, Gong T, Mannem SR, Mitchell BI, Kallianpur KJ, Ndhlovu LC, and Chow DC
- Subjects
- Anti-Retroviral Agents, Biomarkers blood, Cross-Sectional Studies, Female, HIV Infections blood, HIV Infections epidemiology, Hawaii epidemiology, Humans, Male, Middle Aged, Viral Load, Erythrocyte Indices, Erythrocytes cytology, HIV Infections drug therapy, Inflammation pathology, T-Lymphocytes
- Abstract
Background: Chronic inflammation and immune dysfunction occur in human immunodeficiency virus (HIV)-infection despite stable antiretroviral therapy (ART). Red blood cell distribution width (RDW) has been shown to correlate with markers of inflammation in non-HIV conditions. The study objective was to determine associations between RDW with cellular markers of immune activation and immune dysfunction including soluble inflammatory mediators in ART treated HIV infection., Methods: We performed a cross-sectional analysis of the Hawaii Aging with HIV-Cardiovascular study. RDW was defined as one standard deviation of RBC size divided by mean corpuscular volume multiplied by 100%. Correlations were analyzed between RDW, soluble inflammatory biomarkers and T cell activation (CD38 + HLA-DR+), senescence (CD28-CD57+), and immune exhaustion (PD-1, TIGIT, TIM-3 expression)., Results: Of 158 participants analyzed, median age was 50 years, duration of ART 12.6 years, virally suppressed 84.4%, and CD4 count 503 cells/mm3. Significant positive correlations were identified between RDW and soluble biomarkers including sICAM, IL-8, IL-6, SAA, TNF-α, sE-selection, fibrinogen, D-dimer, CRP, CD4/CD8 ratio, and frequency of multiple CD8 T-cell populations such as CD38 + HLA-DR + T-cells, single TIGIT+, and dual expressing of TIGIT + PD1+, TIGIT + TIM3+, and TIM3 + PD1+ CD8+ T-cell subsets (p < .05). Frequencies of CD38 + HLA-DR + CD8+ T-cells and TIGIT + CD8+ T-cells remained significant adjusting for baseline variables (p < .01)., Conclusion: Our study revealed correlations between RDW with systemic inflammatory biomarkers and CD8+ T-cell populations related to immune activation and exhaustion in HIV-infected individuals on ART. Further studies are warranted to determine the utility of RDW as a marker of immune dysregulation in HIV.
- Published
- 2018
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70. In Vitro Blood-Brain Barrier Modeling adapted for Peripheral Blood Mononuclear Cell Transmigration from HIV-Positive Patients for Clinical Research on Therapeutic Drug Intervention.
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Oda R, Shiramizu B, Agsalda-Garcia M, Kettlewell J, and Wojna V
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- Biomedical Research, Cells, Cultured, HIV Seropositivity blood, HIV Seropositivity drug therapy, Humans, Blood-Brain Barrier, Cell Movement, Leukocytes, Mononuclear physiology, Models, Biological
- Abstract
Objective: HIV-associated cognitive impairment (HACI) continues to persist for HIV-seropositive individuals who are on antiretroviral therapy (ART). HACI develops in part when HIV-infected monocytes (MOs) transmigrate through the blood-brain barrier (BBB) and secrete pro-inflammatory cytokines and chemokines, which leads to neuronal damage. In vitro BBB models are important tools that can elucidate mechanisms of MO transmigration. Previously described in vitro BBB models relied on pathology specimens, resulting in potentially variable and inconsistent results. This project reports on a reliable and consistent alternative in vitro BBB model that has the potential to be used in clinical research intervention studies analyzing the effects of ART on the BBB and on MO transmigration., Methods: A bilayer BBB model was established with commercially available astrocytes and endothelial cells on a 3μm PET membrane insert to allow the contact of astrocytic foot processes with endothelial cells. Inserts were cultured in growth medium for 7 days before exposure to HIV- or HIV+ peripheral blood mononuclear cells (PBMCs). PBMCs were allowed to transmigrate across the BBB for 24 hours., Results: Confluency and integrity measurements by trans-endothelial electrical resistance (TEER) (136.7 ± 18.3Ω/cm2) and permeability (5.64 ± 2.20%) verified the integrity of the in vitro BBB model. Transmigrated MOs and non-MOs were collected and counted (6.0x104 MOs; 1.1x105 non-MOs). Markers indicative of glial fibrillary acidic protein (GFAP), von Willebrand factor (vWF), and p-glycoprotein (Pgp) were revealed in immunofluorescence staining (IF), indicating BBB phenotype and functionality., Conclusion: Potential applications for this model include assessing the HIV DNA copy numbers of transmigrated cells (pre- and post-targeted ART) and understanding the role of oxidative stress related to HIV DNA and HACI.
- Published
- 2018
71. Human Papillomavirus-16 DNA Quantitation Differentiates High-Grade Anal Neoplasia.
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Agsalda-Garcia M, Shieh T, Chuang E, Loi N, Milne C, Fang R, Lim E, Killeen J, and Shiramizu B
- Subjects
- Adult, Algorithms, Anal Canal virology, Anus Neoplasms pathology, Early Detection of Cancer, Female, Homosexuality, Male statistics & numerical data, Humans, Male, Mass Screening, Middle Aged, Papillomavirus Infections diagnosis, Anal Canal pathology, Anus Neoplasms diagnosis, Anus Neoplasms virology, Human papillomavirus 16 genetics, Human papillomavirus 16 isolation & purification, Neoplasm Grading, Papillomavirus Infections virology
- Abstract
Background: Due to their higher rates of anal dysplasia/cancer, human immunodeficiency virus (HIV)-positive individuals are recommended to undergo anal dysplasia screening, which consists of anal cytology (AC) and high resolution anoscopy (HRA) with anal biopsy (AB) after abnormal AC result. However, AC variability limits its usefulness. Our objective was to evaluate human papillomavirus (HPV)-16 DNA quantitation as part of the screening algorithm. Methods: HPV-16 was detected in AC specimens from 75 HIV-positive participants using quantitative real-time polymerase chain reaction. AB results were available from 18/44 patients who had abnormal AC. Statistical tests included Mann-Whitney U, Kruskal-Wallis, receiver operating characteristic (ROC) analysis and Kappa coefficient tests. Results: HPV-16 copy numbers differed significantly across AC ( p = 0.001) and AB grades ( p = 0.009). HPV-16 ≥ 65 copies/cell predicted high-grade AB ( p = 0.04). Using this cut-off in comparison to AB, it had better specificity (1.00) than AC (0.75) and specificity (0.77) than qualitative HPV-16 detection (0.38). Also, the Kappa coefficient of the cut-off (κ = 0.649) was higher than AC (κ = 0.557) and qualitative HPV-16 detection (κ = 0.258) to AB. Conclusion: Higher HPV-16 copy numbers corresponded to higher AC and AB grades, suggesting the importance of HPV burden on disease stage. Furthermore, HPV-16 ≥ 65 copies/cell distinguished high-grade disease and demonstrated better sensitivity, specificity, and agreement with AB than AC or qualitative HPV-16 detection. These results support the potential use of HPV quantitation in conjunction with AC in anal dysplasia screening.
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- 2018
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72. Paroxysmal Nocturnal Dyspnea Secondary to Right Ventricular Myxoma: A Novel Presentation of an Unusual Tumor.
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Knight TE, Shiramizu B, Ly P, Thompson KS, and Reddy V
- Abstract
A 14-month-old male presented with paroxysmal nocturnal dyspnea and grade III/VI systolic ejection murmur at the upper left sternal border with an S4 gallop and was subsequently found to have a right ventricular cardiac myxoma. Prior presentations of these tumors have been with exertional syncope and murmur, asymptomatic murmur, or exertional dyspnea; the presentation of such a tumor with paroxysmal nocturnal dyspnea is novel.
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- 2018
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73. Unique Raman Spectroscopic Fingerprints of B-Cell Non-Hodgkin Lymphoma: Implications for Diagnosis, Prognosis and New Therapies.
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Shiramizu B, Oda R, Kamada N, Garcia MA, Shieh T, Maeda TA, Choi SY, Lim E, and Misra A
- Abstract
Objective: Raman spectroscopy is a non-invasive laser-based technique that identifies molecular chemical composition of tissues and cells. The objective of the work was to demonstrate that unique Raman spectroscopic fingerprints of B-cell non-Hodgkin lymphoma cells could be distinguished from normal B-cells., Methods: Normal B-cells and B-cell non-Hodgkin lymphoma cells were mounted on aluminum slides and analyzed by Raman spectroscopy using Asymmetric Least Squares and Principal Component Analysis., Results: Clustering by Principal Component Analysis differentiated normal B-cells from B-cell non-Hodgkin lymphoma cells as well as between the different B-cell non-Hodgkin lymphoma cell types., Conclusions: Raman spectroscopy technology provided a different paradigm in analyzing tumor cells which could be used for diagnosis as well as contribute new information on unique characteristics of cancer cells to understand pathogenesis and potential novel treatments.
- Published
- 2018
74. A Case of Escherichia coli Hemolytic Uremic Syndrome in a 10-Year-Old Male With Severe Neurologic Involvement Successfully Treated With Eculizumab.
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Rasa M, Musgrave J, Abe K, Tanaka L, Xoinis K, Shiramizu B, Foskett G, and Lau R
- Abstract
Hemolytic uremic syndrome (HUS) can be classified as typical and atypical, and the treatment recommendations currently differ between the 2 types. Eculizumab is recommended as first-line treatment for atypical HUS; however, its use in typical HUS has been controversial. We report a case of a 10-year-old male with severe neurologic impairment who was successfully treated with eculizumab, which was started 4 days after onset of neurologic symptoms. Our case supports the use of eculizumab in typical HUS with neurologic involvement, even when given later in the course, as the pathophysiology of typical HUS has been shown to involve activation of the complement pathway, similar to atypical HUS. Further studies are required to establish the efficacy and duration of eculizumab use in this patient population., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2017
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75. Plasminogen Activator Inhibitor-1 Predicts Negative Alterations in Whole-Body Insulin Sensitivity in Chronic HIV Infection.
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Wirunsawanya K, Belyea L, Shikuma C, Watanabe RM, Kohorn L, Shiramizu B, Mitchell BI, Souza SA, Keating SM, Norris PJ, Ndhlovu LC, and Chow D
- Subjects
- Female, Humans, Longitudinal Studies, Male, Middle Aged, HIV Infections complications, Insulin Resistance, Plasminogen Activator Inhibitor 1 blood
- Abstract
Plasminogen activator inhibitor type 1 (PAI-1), a key negative regulator of fibrinolysis, has been investigated to be one of the potential mechanisms of the development of impaired insulin sensitivity, insulin resistance, and diabetes mellitus. Because chronically stable HIV-infected individuals frequently develop abnormal glucose metabolism, including insulin resistance and diabetes mellitus, we postulated that PAI-1 could be one of the multifactorial pathogenic roles in the development of impaired insulin sensitivity and insulin resistance among chronic HIV-infected individuals. From our longitudinal cohort study, we selectively recruited chronically stable HIV-infected individuals without diagnosis of diabetes mellitus at baseline (N = 62) to analyze the correlation of baseline inflammatory cytokines, including PAI-1 and whole-body insulin sensitivity, with 2-year follow-up, as measured by Matsuda Index. We found a negative correlation between baseline PAI-1 and Matsuda Index (r = -0.435, p = .001) and a negative correlation between baseline PAI-1 and Matsuda Index at 2 years (r = -0.377, p = .005). In a linear regression model that included age, total body fat mass percentage, serum amyloid A, and family history of diabetes mellitus, PAI-1 still remained significantly associated with Matsuda Index at 2-year follow-up (β = -.397, p = .002). Our longitudinal study suggests that PAI-1 is an independent predictor of impaired insulin sensitivity among chronic HIV-infected individuals.
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- 2017
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76. Brief Report: CD14+ Enriched Peripheral Cells Secrete Cytokines Unique to HIV-Associated Neurocognitive Disorders.
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Agsalda-Garcia MA, Sithinamsuwan P, Valcour VG, Chalermchai T, Tipsuk S, Kuroda J, Nakamura C, Ananworanich J, Zhang G, Schuetz A, Slike BM, and Shiramizu B
- Subjects
- AIDS Dementia Complex physiopathology, Cytokines, Gene Expression Profiling, HIV Infections physiopathology, Humans, Monocytes, Viral Load, AIDS Dementia Complex metabolism, HIV Infections metabolism, Leukocytes, Mononuclear metabolism, Lipopolysaccharide Receptors metabolism
- Abstract
Monocytes play a vital role in HIV-associated neurocognitive disorder (HAND), postulated to transport HIV into the brain and secrete pro-inflammatory cytokines. We analyzed cytokines released by cultured peripheral blood mononuclear cells enriched with the CD14 marker isolated from HIV-infected individuals with HAND and normal cognition (NC) in combination antiretroviral therapy naive and after 1 year on treatment. Interleukin-8 and monocyte chemoattractant protein-1 levels were higher in HAND compared with NC at baseline (P = 0.002 and P < 0.0001). These cytokines remained higher in HAND patients 1 year after combination antiretroviral therapy and were significant when NC patients who were initially HAND were excluded (P = 0.012 and P = 0.002). Both correlated with baseline CD14 peripheral blood mononuclear cell HIV DNA levels supporting the role of HIV DNA reservoir size and monocyte cytokines in HAND persistence.
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- 2017
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77. Leading by Success: Impact of a Clinical and Translational Research Infrastructure Program to Address Health Inequities.
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Shiramizu B, Shambaugh V, Petrovich H, Seto TB, Ho T, Mokuau N, and Hedges JR
- Abstract
Building research infrastructure capacity to address clinical and translational gaps has been a focus of funding agencies and foundations. Clinical and Translational Sciences Awards, Research Centers in Minority Institutions Infrastructure for Clinical and Translational Research (RCTR), and the Institutional Development Award Infrastructure for Clinical and Translational Research funded by the US government to fund clinical translational research programs have existed for over a decade to address racial and ethnic health disparities across the USA. While the impact on the nation's health cannot be made in a short period, assessment of a program's impact could be a litmus test to gauge its effectiveness at the institution and communities. We report the success of a Pilot Project Program in the University of Hawaii RCTR Award in advancing careers of emerging investigators and community collaborators. Our findings demonstrated that the investment has a far-reaching impact on engagement with community-based research collaborators, career advancement of health disparity investigators, and favorable impacts on health policy.
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- 2016
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78. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.
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Lamers SL, Rose R, Maidji E, Agsalda-Garcia M, Nolan DJ, Fogel GB, Salemi M, Garcia DL, Bracci P, Yong W, Commins D, Said J, Khanlou N, Hinkin CH, Sueiras MV, Mathisen G, Donovan S, Shiramizu B, Stoddart CA, McGrath MS, and Singer EJ
- Subjects
- Humans, Longitudinal Studies, Real-Time Polymerase Chain Reaction, Anti-Retroviral Agents therapeutic use, Autopsy, DNA, Viral analysis, HIV Infections drug therapy, HIV Infections virology, Viral Load
- Abstract
Unlabelled: HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis., Importance: It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is, "Where is HIV hiding?" A well-studied HIV reservoir is "resting" T cells, which can be isolated from blood products and succumb to cART once activated. Less-studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since <2% of body lymphocytes actually reside in blood. We examined 229 varied autopsy specimens from 20 HIV(+) participants who died while on cART and identified that >50% of tissues were HIV infected. Additionally, we identified considerable pathology in participants' tissues, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. This study substantiates that tissue-associated HIV is present despite cART and can inform future studies into HIV persistence., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
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- 2016
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79. Peripheral Primitive Neuroectodermal Tumor and Neurofibromatosis Type 1 in an Adolescent Male.
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Knight TE, Knight SW, Kyono W, Thompson K, Hicks J, and Shiramizu B
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- Adolescent, Humans, Male, Head and Neck Neoplasms pathology, Neoplasms, Second Primary pathology, Neuroectodermal Tumors, Primitive, Peripheral pathology, Neurofibromatosis 1 pathology
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- 2016
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80. Paediatric non-Hodgkin lymphoma - perspectives in translational biology.
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Shiramizu B, Mussolin L, Woessmann W, and Klapper W
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- Adolescent, Child, Child, Preschool, Female, Genetic Therapy methods, Humans, Immunotherapy methods, Infant, Lymphoma, Non-Hodgkin genetics, Male, Molecular Diagnostic Techniques, Prognosis, Salvage Therapy methods, Salvage Therapy trends, Translational Research, Biomedical methods, Translational Research, Biomedical trends, Lymphoma, Non-Hodgkin diagnosis, Lymphoma, Non-Hodgkin therapy
- Abstract
Exciting advances have been achieved for infants, children and adolescents diagnosed with, and treated for, non-Hodgkin lymphoma (NHL). In spite of these successes, new frontiers are being paved to improve the prognosis for those who relapse or have resistant disease. This review summarizes some of the novel approaches and ideas in NHL monitoring, diagnosis and treatment as discussed at the 5th International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma on October 22nd-24th 2015 in Varese, Italy., (© 2016 John Wiley & Sons Ltd.)
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- 2016
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81. Nef exosomes isolated from the plasma of individuals with HIV-associated dementia (HAD) can induce Aβ(1-42) secretion in SH-SY5Y neural cells.
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Khan MB, Lang MJ, Huang MB, Raymond A, Bond VC, Shiramizu B, and Powell MD
- Subjects
- AIDS Dementia Complex drug therapy, AIDS Dementia Complex physiopathology, AIDS Dementia Complex virology, Adult, Aged, Amyloid beta-Peptides genetics, Amyloid beta-Peptides metabolism, Anti-HIV Agents therapeutic use, Cell Line, Tumor, Exosomes pathology, Female, Gene Expression Regulation, HEK293 Cells, HIV-1 drug effects, HIV-1 physiology, Humans, Male, Middle Aged, Neurons metabolism, Neurons pathology, Peptide Fragments genetics, Peptide Fragments metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Viral Load, nef Gene Products, Human Immunodeficiency Virus metabolism, AIDS Dementia Complex blood, Amyloid beta-Peptides biosynthesis, Exosomes metabolism, Peptide Fragments biosynthesis, RNA, Messenger biosynthesis, RNA, Viral blood, nef Gene Products, Human Immunodeficiency Virus genetics
- Abstract
In the era of combined antiretroviral therapy (CART), many of the complications due to HIV-1 infection have diminished. One exception is HIV-associated neurocognitive disorder (HAND). HAND is a spectrum of disorders in cognitive function that ranges from asymptomatic disease to severe dementia (HAD). The milder form of HAND has actually remained the same or slightly increased in prevalence in the CART era. Even in individuals who have maintained undetectable HIV RNA loads, viral proteins such as Nef and Tat can continue to be expressed. In this report, we show that Nef protein and nef messenger RNA (mRNA) are packaged into exosomes that remain in circulation in patients with HAD. Plasma-derived Nef exosomes from patients with HAD have the ability to interact with the neuroblastoma cell line SH-SY5Y and deliver nef mRNA. The mRNA can induce expression of Nef in target cells and subsequently increase expression and secretion of beta-amyloid (Aβ) and Aβ peptides. Increase secretion of amyloid peptide could contribute to cognitive impairment seen in HAND.
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- 2016
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82. Addressing Risk and Reluctance at the Nexus of HIV and Anal Cancer Screening.
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Ka'opua LS, Cassel K, Shiramizu B, Stotzer RL, Robles A, Kapua C, Orton M, Milne C, and Sesepasara M
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- Adult, Aged, Anus Neoplasms diagnosis, Cultural Competency, Early Detection of Cancer, Female, Focus Groups, HIV Infections diagnosis, HIV Infections psychology, Hawaii, Health Knowledge, Attitudes, Practice, Health Promotion, Health Status Disparities, Humans, Male, Middle Aged, Anus Neoplasms psychology, Native Hawaiian or Other Pacific Islander psychology, Patient Acceptance of Health Care ethnology, Patient Acceptance of Health Care psychology
- Abstract
Anal cancer disproportionately burdens persons living with human immunodeficiency virus (PLHIV) regardless of natal sex, sexual orientation, gender expression, and ethnic identity. Culturally competent communications are recommended to address health disparities, with sociocultural relevance ensured through constituent dialogic processes. Results are presented from six provider focus groups conducted to inform the promotion/education component of a Hawai'i-based project on anal cancer screening tools. Krueger's focus group methodology guided discussion queries. Verbatim transcripts of digitally recorded discussions were analyzed using grounded theory and PEN-3 procedures. Adherence to an audit trail ensured analytic rigor. Grounded theory analysis detected the overall theme of risk and reluctance to anal cancer screening, characterized by anal cancer not being "on the radar" of PLHIV, conflicting attributions of the anus and anal sex, fear of sex-shaming/-blaming, and other interrelated conceptual categories. PEN-3 analysis revealed strategies for destigmatizing anal cancer, through "real talk" (proactive, candid, nonjudgmental discussion) nested in a framework of sexual health and overall well-being, with additional tailoring for relevance to Native Hawaiians/Pacific Islanders, transgender persons, and other marginalized groups. Application of strategies for health practice are specific to the Hawai'i context, yet may offer considerations for developing strengths-based, culturally relevant screening promotion/education with diverse PLHIV in other locales., (© 2015 Society for Public Health Education.)
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- 2016
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83. Human Papillomavirus at Multiple Sites Associated with Anal Squamous Intraepithelial Lesions in HIV-Seropositive Individuals.
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Chuang E, Lim E, Milne C, Zhu X, Agsalda M, Killeen J, Miller FD, Hernandez BY, and Shiramizu B
- Abstract
Objective: HIV-Seropositive patients have higher risk of HPV infection even on anti-retroviral therapy. Infection with high-risk HPV genotypes can cause dysplasia leading to cancer. This study assessed HPV at different anatomical sites in HIV-seropositive individuals and factors associated with anal squamous intraepithelial lesions (ASIL)., Methods: Specimens were obtained from multiple anatomical sites for each participant in conjunction with routine screening for anal dysplasia. Female specimens included cervical and anal cytologies and oral wash. Male specimens included anal cytologies, oral wash, and exfoliated cells from penile head, penile shaft, scrotum, and from uncircumcised subjects, inner foreskin. Demographic and clinical characteristics were recorded. Following DNA extraction, HIV DNA copy was assessed by qPCR; HPV was genotyped. Statistical analyses included calculation of odds ratios (OR) and 95% confidence intervals (CI), t-tests or Mann-Whitney tests., Results: Males were more likely to have ASIL: 29/50 (58%) compared to 1/11 females (9%) (OR=13.81, 95% CI: 1.64-116.32). HPV 6 or 11 in anal specimens was significantly associated with ASIL (OR= 6.29, 95% CI: 1.49-26.44). Number of HPV genotypes in anal specimens was also significant: ASIL+ (3.4 ± 3.1) versus ASIL- (1.6 ± 3.1) (p=0.009). Among 44 males, HPV was detected from at least one anatomical site for 33 participants (75%): 27 anus (61%), 19 oral wash (44%), 17 penile shaft (39%), 11 scrotum (26%), 10 penile head (23%), 0 foreskin. Detection of HPV in penile shaft specimens was significantly associated with ASIL (OR=6.79, 95% CI: 1.57-29.36) as was number of HPV genotypes in penile shaft specimens: ASIL+ (2.4 ± 4.0) versus ASIL- (0.6 ± 1.7) (p=0.025). Only 1/11 females had ASIL; only 1/11 females had cervical dysplasia: OR was not estimable due to small numbers., Conclusions: Males were more prone to ASIL than females. HPV at anal as well as non-anal sites may be indicative of ASIL.
- Published
- 2016
84. Loss of CCR2 expressing non-classical monocytes are associated with cognitive impairment in antiretroviral therapy-naïve HIV-infected Thais.
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Ndhlovu LC, D'Antoni ML, Ananworanich J, Byron MM, Chalermchai T, Sithinamsuwan P, Tipsuk S, Ho E, Slike BM, Schuetz A, Zhang G, Agsalda-Garcia M, Shiramizu B, Shikuma CM, and Valcour V
- Subjects
- Adult, Asian People, DNA, Viral analysis, Female, Flow Cytometry, Humans, Male, Monocytes immunology, Receptors, CCR2 immunology, Thailand, AIDS Dementia Complex immunology, Cognition Disorders immunology, Monocytes virology
- Abstract
HIV DNA in monocytes has been linked to HIV-associated neurocognitive disorders (HAND), however, characterization of monocyte subsets associated with HAND remains unclear. We completed a prospective study of antiretroviral therapy-naïve, HIV-infected Thais, with varying degrees of cognitive impairment, compared to HIV-uninfected controls. Monocyte subsets' CCR2, CCR5 and CD163 expression were profiled and inflammatory markers in plasma and cerebrospinal fluid (CSF), measured. Lower numbers of CCR2(+)non-classical monocytes were associated with worse neuropsychological test performance (r=0.43, p=0.024). CCR2(+)non-classical monocyte count inversely correlated with CSF neopterin (r=-0.43, p=0.035) and plasma TNF-α levels (r=-0.40, p=0.041). These data benchmark CCR2(+)non-classical monocytes as an independent index of cognitive impairment., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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85. Impact of persistent minimal residual disease post-consolidation therapy in children and adolescents with advanced Burkitt leukaemia: a Children's Oncology Group Pilot Study Report.
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Shiramizu B, Goldman S, Smith L, Agsalda-Garcia M, Galardy P, Perkins SL, Frazer JK, Sanger W, Anderson JR, Gross TG, Weinstein H, Harrison L, Barth MJ, Mussolin L, and Cairo MS
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Neoplasm, Residual, Pilot Projects, Real-Time Polymerase Chain Reaction, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Burkitt Lymphoma blood, Burkitt Lymphoma drug therapy, Central Nervous System Neoplasms blood, Central Nervous System Neoplasms drug therapy, Consolidation Chemotherapy
- Abstract
Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French-British-American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease (MRD) was assessed by real-time polymerase chain reaction at the end of induction (EOI) and consolidation (EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
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86. Rituximab with chemotherapy in children and adolescents with central nervous system and/or bone marrow-positive Burkitt lymphoma/leukaemia: a Children's Oncology Group Report.
- Author
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Goldman S, Smith L, Galardy P, Perkins SL, Frazer JK, Sanger W, Anderson JR, Gross TG, Weinstein H, Harrison L, Shiramizu B, Barth M, and Cairo MS
- Subjects
- Adolescent, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antibodies, Monoclonal, Murine-Derived adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Marrow pathology, Burkitt Lymphoma genetics, Child, Consolidation Chemotherapy, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Cytarabine administration & dosage, Cytarabine adverse effects, Disease-Free Survival, Doxorubicin administration & dosage, Doxorubicin adverse effects, Drug Administration Schedule, Etoposide administration & dosage, Etoposide adverse effects, Female, Genes, myc, Humans, Immunotherapy, Infusions, Intravenous, Kaplan-Meier Estimate, Lymphoma, B-Cell genetics, Maintenance Chemotherapy, Male, Methotrexate administration & dosage, Methotrexate adverse effects, Prednisone administration & dosage, Prednisone adverse effects, Remission Induction, Rituximab, Typhlitis chemically induced, Vincristine administration & dosage, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy, Central Nervous System Neoplasms drug therapy, Lymphoma, B-Cell drug therapy
- Abstract
Children and adolescents with Burkitt Lymphoma (BL) and combined central nervous system (CNS) and bone marrow involvement still have a poor prognosis with chemotherapy alone. We therefore investigated in children and adolescents with bone marrow (≥25% blasts) and/or CNS-positive Burkitt lymphoma the chemoimmunotherapy combination of rituximab (375 mg/m(2) ) and the standard chemotherapy arm of our previously reported French-American-British (FAB) Lymphome Malins de Burkitt (LMB) 96 trial. Central pathological and cytogenetic characterization was also performed. There were 40 evaluable patients with Burkitt histology (25 with leukaemia and 15 with CNS disease ± leukaemia). The chemoimmunotherapy regimen was well tolerated. The incidence of grade III/IV mucositis during induction cycles with combined chemotherapy and rituximab was 31% and 26%, respectively. The 3-year event-free survival (EFS)/overall survival (OS) was 90% (95% confidence interval [CI], 76-96%) in the entire cohort and 93% (95% CI, 61-99%) in patients with CNS disease. Based on the results of this trial, an international randomized study of FAB/LMB 96 chemotherapy ± rituximab for high-risk patients is currently under investigation., (© 2014 John Wiley & Sons Ltd.)
- Published
- 2014
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87. Different levels of HIV DNA copy numbers in cerebrospinal fluid cellular subsets.
- Author
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Agsalda-Garcia M, Shiramizu B, Melendez L, Plaud M, Liang CY, and Wojna V
- Subjects
- Adult, Cohort Studies, Female, HIV Infections complications, Hawaii, Humans, Lipopolysaccharide Receptors metabolism, Lymphocytes metabolism, Male, Middle Aged, Monocytes metabolism, Puerto Rico, Sampling Studies, Cognition Disorders etiology, DNA, Viral cerebrospinal fluid, HIV Infections cerebrospinal fluid
- Abstract
Inequities in the incidence of HIV infection and AIDS with continued persistence of HIV-associated neurocognitive disorders (HAND) exist in populations in Hawaii (HI) and Puerto Rico (PR). We previously reported that peripheral monocyte HIV DNA levels are high in patients in Hawaii with HAND and we now hypothesize that similar findings would be observed in the cerebrospinal fluid (CSF) cellular subsets. Cerebrospinal fluid cells were obtained from patients from PR and HI undergoing neurocognitive testing and sorted into monocytes (CD14+) and lymphocytes (CD14-) and HIV DNA was measured. From six PR subjects (three HAND, three normal cognition, NC) and six HI subjects (three HAND, three NC), HIV DNA burden in CD14+ cells was higher in HAND than NC patients; NC patients had higher HIV DNA burden in CD14-cells versus HAND. Differences in HIV DNA burden in particular CSF cellular subsets suggest that HIV DNA burden may play a role in HAND neuropathogenesis.
- Published
- 2013
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88. Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukaemia: a Children's Oncology Group report.
- Author
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Barth MJ, Goldman S, Smith L, Perkins S, Shiramizu B, Gross TG, Harrison L, Sanger W, Geyer MB, Giulino-Roth L, and Cairo MS
- Subjects
- Adolescent, Adult, Age Factors, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Drug Administration Schedule, Half-Life, Humans, L-Lactate Dehydrogenase blood, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell pathology, Methotrexate therapeutic use, Neoplasm Staging, Pilot Projects, Prednisone therapeutic use, Rituximab, Vincristine therapeutic use, Young Adult, Antibodies, Monoclonal, Murine-Derived blood, Antineoplastic Agents blood, Lymphoma, B-Cell blood
- Abstract
The ANHL01P1 trial was undertaken to determine pharmacokinetics and safety following the addition of rituximab to French-American-British/Lymphome Malins de Burkitt (FAB/LMB96) chemotherapy in 41 children and adolescents with Stage III/IV mature B-cell lymphoma/leukaemia. Patients received rituximab (375 mg/m(2) ) days -2 and 0 of two induction cycles and day 0 of two consolidation cycles. Highest peak levels were achieved following the second dose of each induction cycle [299 ± 19 and 384 ± 25 μg/ml (Group-B); 245 ± 31 and 321 ± 32 μg/ml (Group-C)] with sustained troughs and t½ of 26-29 d. Rituximab can be safely added to FAB chemotherapy with high early rituximab peak/trough levels and a long t½., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
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89. HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients.
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Valcour VG, Ananworanich J, Agsalda M, Sailasuta N, Chalermchai T, Schuetz A, Shikuma C, Liang CY, Jirajariyavej S, Sithinamsuwan P, Tipsuk S, Clifford DB, Paul R, Fletcher JL, Marovich MA, Slike BM, DeGruttola V, and Shiramizu B
- Subjects
- Adult, Brain metabolism, Brain pathology, Brain virology, Cognition Disorders etiology, Cytokines blood, Cytokines cerebrospinal fluid, DNA, Viral genetics, Female, HIV drug effects, HIV genetics, HIV physiology, HIV Infections complications, HIV Infections virology, Host-Pathogen Interactions drug effects, Humans, Lipopolysaccharide Receptors metabolism, Male, Monocytes metabolism, Monocytes pathology, Monocytes virology, Multiplex Polymerase Chain Reaction, Multivariate Analysis, Prospective Studies, ROC Curve, Regression Analysis, Risk Factors, Antiretroviral Therapy, Highly Active, Cognition Disorders diagnosis, DNA, Viral metabolism, HIV Infections drug therapy
- Abstract
Objectives: Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury., Methods: We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF)., Results: The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions., Interpretation: Reservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.
- Published
- 2013
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90. Presence of high-risk human papillomavirus genotype and human immunodeficiency virus DNA in anal high-grade and low-grade squamous intraepithelial lesions.
- Author
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Shiramizu B, Liang CY, Agsalda-Garcia M, Nagata I, Milne C, Zhu X, Killeen J, Berry JM, and Goodman MT
- Subjects
- Adolescent, Adult, Aged, Anal Canal pathology, Anal Canal virology, Anus Neoplasms genetics, Anus Neoplasms pathology, Coinfection genetics, Coinfection virology, Female, Genotype, HIV Infections genetics, Humans, Male, Middle Aged, Papillomavirus Infections genetics, Precancerous Conditions genetics, Precancerous Conditions pathology, Prospective Studies, Risk Factors, Young Adult, Anus Neoplasms virology, DNA, Viral genetics, HIV Infections complications, HIV-1 genetics, Papillomaviridae genetics, Papillomavirus Infections complications, Precancerous Conditions virology
- Abstract
Human immunodeficiency virus type 1 (HIV)-infected individuals are at risk for anal cancer, which is caused by human papillomavirus (HPV). The relationship between HIV and HPV that leads to anal cancer remains unclear. Recent data, however, suggest that the continued persistence of HIV DNA in patients treated with combined antiretroviral therapy leads to progression of HIV disease and other HIV-associated complications. Therefore, we investigated the relationship among anal low- and high-grade squamous intraepithelial lesions (LGSIL/HGSIL), high-risk HPV genotypes, and high HIV DNA copy numbers. Anal cytology specimens were assayed for HPV genotype and HIV DNA copy number. High-risk HPV genotypes (odds ratio OR: 3.73; 95% confidence interval CI: 1.08-12.91; p=0.04) and high HIV DNA copy numbers (OR(per 100 HIV DNA copies): 1.13; 95% CI: 1.01-1.27, p=0.04) were both associated with LGSIL/HGSIL. When considering both high-risk HPV genotypes and HIV DNA copy numbers in predicting LGSIL/HGSIL, HIV DNA copy number was significant (OR(per 100 HIV DNA copies): 1.09; 95% CI: 0.96-1.23, p=0.04) but not high-risk HPV genotypes (OR: 2.30, p=0.28), which did not change when adjusted for nadir CD4 cell count and HIV RNA levels. The findings warrant further investigation of HIV DNA and its relationship with HPV in LGSIL/HGSIL pathogenesis.
- Published
- 2013
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91. Cognitive performance related to HIV-1-infected monocytes.
- Author
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Kusao I, Shiramizu B, Liang CY, Grove J, Agsalda M, Troelstrup D, Velasco VN, Marshall A, Whitenack N, Shikuma C, and Valcour V
- Subjects
- Adult, Aged, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, Cohort Studies, DNA Viruses metabolism, Female, Human Immunodeficiency Virus Proteins genetics, Human Immunodeficiency Virus Proteins metabolism, Humans, Male, Middle Aged, Monocytes metabolism, Monocytes virology, Neuropsychological Tests, Cognition Disorders etiology, Cognition Disorders virology, HIV Infections complications, HIV Infections pathology, Monocytes pathology
- Abstract
The effect that HIV type 1 (HIV) has on neurocognition is a dynamic process whereby peripheral events are likely involved in setting the stage for clinical findings. In spite of antiretroviral therapy (ART), patients continue to be at risk for HIV-associated neurocognitive disorders (HAND), which might be related to persistence of inflammation. In a yearly assessment of HIV DNA levels in activated monocytes, increased HIV DNA copies were found in patients with persistent HAND. Furthermore, activated monocytes from patients with high HIV DNA copies secreted more inflammatory cytokines. Since these activated monocytes traffic to the CNS and enter the brain, they may contribute to an inflammatory environment in the CNS that leads to HAND.
- Published
- 2012
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92. Regional cortical thinning associated with detectable levels of HIV DNA.
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Kallianpur KJ, Kirk GR, Sailasuta N, Valcour V, Shiramizu B, Nakamoto BK, and Shikuma C
- Subjects
- Adult, Female, HIV Infections blood, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Retrospective Studies, Brain pathology, DNA, Viral blood, HIV Infections pathology, HIV Infections virology
- Abstract
High levels of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs), and specifically within CD14+ blood monocytes, have been found in HIV-infected individuals with neurocognitive impairment and dementia. The failure of highly active antiretroviral therapy (HAART) to eliminate cognitive dysfunction in HIV may be secondary to persistence of HIV-infected PBMCs which cross the blood-brain barrier, leading to perivascular inflammation and neuronal injury. This study assessed brain cortical thickness relative to HIV DNA levels and identified, we believe for the first time, a neuroimaging correlate of detectable PBMC HIV DNA in subjects with undetectable HIV RNA. Cortical thickness was compared between age- and education-matched groups of older (>40 years) HIV-seropositive subjects on HAART who had detectable (N = 9) and undetectable (N = 10) PBMC HIV DNA. Statistical testing revealed highly significant (P < 0.001) cortical thinning associated with detectable HIV DNA. The largest regions affected were in bilateral insula, orbitofrontal and temporal cortices, right superior frontal cortex, and right caudal anterior cingulate. Cortical thinning correlated significantly with a measure of psychomotor speed. The areas of reduced cortical thickness are key nodes in cognitive and emotional processing networks and may be etiologically important in HIV-related neurological deficits.
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- 2012
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93. A Community-Based Approach to Enhancing Anal Cancer Screening in Hawaii's HIV-Infected Ethnic Minorities.
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Shiramizu B, Milne C, Terada K, Cassel K, Matsuno RK, Killeen J, Liang CY, Tachibana F, Sheeran T, Weihe J, and Goodman MT
- Abstract
Objective: Disparities in anal cancer incidence among Hawaii's HIV-infected minority population is an emerging health concern. Although anal cytology/anoscopy are effective anal cancer screening tools, social barriers exist that prevent individuals from seeking appropriate care., Design: Community based participatory research (CBPR) principles were applied to develop resources, including testing a self-obtained anal specimen procedure, to increase anal cancer screening among Hawaii's underserved/ minority populations., Methods: A team of community members, academic researchers, and health care providers developed culturally-sensitive educational/recruitment materials regarding anal cancer risk targeting underserved/minority HIV-infected individuals. Self- and health care provider (HCP)-obtained anal cancer screening specimens were reviewed for cytology and tested for human papillomavirus DNA. A follow-up evaluation elicited feedback on attitudes and experiences., Results: Community discussion sessions identified key messages about anal cancer, anal cancer screening, and HPV infection for materials and were used, that successfully recruited 46 individuals (38 males/8 females; 9 Native Hawaiians/Pacific Islanders/Asians, 2 Blacks, 6 Hispanics, 6 American Indian/Alaskan Natives, 23 Whites). Concordance in cytology results between self- and HCP-obtained specimens was moderated (kappa=0.37) with the perception that the self-obtained specimen procedure was private (93%), safe (100%), and easy to manage (100%); and a majority (92%) willing to use the self-obtained method again., Conclusions: CBPR was a practical approach in engaging Hawaii's HIV-infected minority participation in anal cancer screening research. Community outreach and recruitment efforts suggested that self-obtained screening specimens could be an acceptable and effective means to reach Hawaii's HIV-infected ethnic minorities.
- Published
- 2012
- Full Text
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94. Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV.
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Shikuma CM, Nakamoto B, Shiramizu B, Liang CY, DeGruttola V, Bennett K, Paul R, Kallianpur K, Chow D, Gavegnano C, Hurwitz SJ, Schinazi RF, and Valcour VG
- Subjects
- AIDS Dementia Complex pathology, AIDS Dementia Complex virology, Adult, Anti-Retroviral Agents metabolism, Anti-Retroviral Agents pharmacology, CD4 Lymphocyte Count, Cognition, Cognition Disorders virology, Cross-Sectional Studies, Female, HIV Infections metabolism, HIV Infections pathology, HIV Infections virology, HIV-1 metabolism, Humans, Longitudinal Studies, Macrophages metabolism, Male, Middle Aged, Monocytes metabolism, Neuropsychological Tests, Predictive Value of Tests, Prospective Studies, Statistics, Nonparametric, Cognition Disorders pathology, HIV-1 pathogenicity, Macrophages drug effects, Monocytes drug effects
- Abstract
Background: Monocytes transmigrating to the brain play a central role in HIV neuropathology. We hypothesized that the continued existence of neurocognitive impairment (NCI) despite potent antiretroviral (ARV) therapy is mediated by the inability of such therapy to control this monocyte/macrophage reservoir., Methods: Cross-sectional and longitudinal analyses were conducted within a prospectively enrolled cohort. We devised a monocyte efficacy (ME) score based on the anticipated effectiveness of ARV medications against monocytes/macrophages using published macrophage in vitro drug efficacy data. We examined, within an HIV neurocognitive database, its association with composite neuropsychological test scores (NPZ8) and clinical cognitive diagnoses among subjects on stable ARV medications unchanged for >6 months prior to assessment., Results: Among 139 subjects on ARV therapy, higher ME score correlated with better NPZ8 performance (r=0.23, P<0.01), whereas a score devised to quantify expected penetration effectiveness of ARVs into the brain (CPE score) did not (r=0.12, P=0.15). In an adjusted model (adjusted r(2)=0.12), ME score (β=0.003, P=0.02), CD4(+) T-cell nadir (β=0.001, P<0.01) and gender (β=-0.456, P=0.02) were associated with NPZ8, whereas CPE score was not (β=0.003, P=0.94). A higher ME score was associated with better clinical cognitive status (P<0.01). With a range of 12.5-433.0 units, a 100-unit increase in ME score resulted in a 10.6-fold decrease in the odds of a dementia diagnosis compared with normal cognition (P=0.01)., Conclusions: ARV efficacy against monocytes/macrophages correlates with cognitive function in HIV-infected individuals on ARV therapy within this cohort. If validated, efficacy against monocytes/macrophages may provide a new target to improve HIV NCI.
- Published
- 2012
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95. Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report.
- Author
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Shiramizu B, Goldman S, Kusao I, Agsalda M, Lynch J, Smith L, Harrison L, Morris E, Gross TG, Sanger W, Perkins S, and Cairo MS
- Subjects
- Adolescent, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Epidemiologic Methods, Genes, Immunoglobulin Heavy Chain, Genes, Neoplasm, Humans, Lymphoma, B-Cell genetics, Lymphoma, B-Cell pathology, Neoplasm Staging, Neoplasm, Residual, Recurrence, Rituximab, Young Adult, Lymphoma, B-Cell drug therapy
- Abstract
Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients (P = 0·40). At EOT, only 13/32 patients had MRD data available with one relapse in the MRD-positive group and no recurrences in the MRD-negative group (P = 0·077). The study demonstrated molecular-disseminated disease in which IgIGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL., (© 2011 Blackwell Publishing Ltd.)
- Published
- 2011
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96. Translational research in NeuroAIDS: a neuroimmune pharmacology-related course.
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Brown A, Shiramizu B, Nath A, and Wojna V
- Subjects
- Allergy and Immunology education, Humans, Internet, Mentors, Minority Groups, Neurosciences education, Pharmacology education, AIDS Dementia Complex, Education, Distance methods, Education, Medical, Graduate methods, Translational Research, Biomedical education
- Abstract
Neuroimmune pharmacology (NIP) can be considered a multidisciplinary science where areas of neuroscience, immunology, and pharmacology intersect in neurological disorders. The R25 training program titled "Translational Research in NeuroAIDS and Mental Health (TR-NAMH): An innovative mentoring program to promote diversity in NeuroAIDS Research (R25 MH080661)" at the Johns Hopkins University is a web-based interactive course with the goal to improve the capacity of high quality research by developing mentoring programs for (1) doctoral and postdoctoral candidates and junior faculty from racial and ethnic minorities and (2) non-minority individuals at the same levels, whose research focuses on NeuroAIDS disparity issues such as HIV-associated neurocognitive disorders (HAND). This web-based interactive course overcomes the limitations of traditional education such as access to expert faculty and financial burden of scientists from racial and ethnic minority groups in the field of NeuroAIDS research and NIP and identifies rich nurturing environments for investigators to support their careers. The TR-NAMH program identifies a cadre of talented students and investigators eager to commit to innovative educational and training sessions in NeuroAIDS and NIP. The interplay between NIP changes precipitated by HIV infection in the brain makes the study of HAND an outstanding way to integrate important concepts from these two fields. The course includes activities besides those related to didactic learning such as research training and long-term mentoring; hence, the newly learned topics in NIP are continually reinforced and implemented in real-time experiences. We describe how NIP is integrated in the TR-NAMH program in the context of HAND.
- Published
- 2011
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97. RMATRIX - Clinical Translational Research Award.
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Hedges JR, Shiramizu B, and Seto T
- Subjects
- Hawaii, Humans, Organizational Objectives, Awards and Prizes, Schools, Medical, Translational Research, Biomedical
- Published
- 2011
98. Mitochondrial DNA in residual leukemia cells in cerebrospinal fluid in children with acute lymphoblastic leukemia.
- Author
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Egan K, Kusao I, Troelstrup D, Agsalda M, and Shiramizu B
- Abstract
Unlabelled: This feasibility study was designed to assess the ability to measure mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) cells that contributed to minimal disease/persistent or residual disease (MD/PRD) from children with acute lymphoblastic leukemia (ALL). Increase in mtDNA copies in cancer cells has been suggested to play a role in MD/PRD. CSF as well as blood specimens from 6 children were assayed for MD/PRD and mtDNA copy numbers by quantitative real-time polymerase chain reaction. Of 7 MD/PRD-positive specimens, 6 had increased mtDNA copy numbers; while 11 MD/PRD-negative specimens had no increase in mtDNA copy numbers, p < 0.003. This is the first proof-of-concept study to measure mtDNA copy numbers in MD/PRD-positive CSF specimens from children with ALL. Increase of mtDNA copy numbers in MD/PRD childhood ALL cells and its significance as a mechanism for recurrence requires further investigation., Keywords: Minimal residual disease; Acute lymphoblastic leukemia; Central nervous system; Cerebrospinal fluid; Mitochondria.
- Published
- 2010
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99. Incident neuropathy in HIV-infected patients on HAART.
- Author
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Nakamoto BK, McMurtray A, Davis J, Valcour V, Watters MR, Shiramizu B, Chow DC, Kallianpur K, and Shikuma CM
- Subjects
- Adult, Female, HIV Infections complications, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Risk Factors, AIDS-Associated Nephropathy epidemiology, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy
- Abstract
We determined the incidence of and risk factors for distal sensory polyneuropathy (DSP) in individuals on HAART. Sixty-one HIV-positive subjects on HAART for at least 6 months and neuropathy free were retrospectively selected. The study included subjects who had previously tolerated d-drugs without developing DSP. Neuropathy incidence over 4 years was calculated. Cox proportional hazards models were used to determine risk factors associated with incident DSP. Nineteen subjects developed DSP over a mean follow-up of 2.4 years. Subjects never treated with a d-drug developed DSP at a rate of 21 cases per 100 person-years (95% CI, 8.9-33.7). Subjects with a history of d-drug treatment but not on a d-drug at enrollment developed DSP at a rate of 17 cases per 100 person-years (95% CI, 2.1-31.8). Those on d-drug treatment developed DSP at a rate of 25 cases per 100 person-years (95% CI, 8.7-41.6). Multivariable analysis identified age [hazard ratio (HR) = 1.09; p < 0.01] and low CD4(+) nadir [hazard ratio (HR) = 0.79; p = 0.03] as significant risk factors. Current or prior history of treatment with d-drug was not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP. Age and low CD4(+) are risk factors for incident DSP. However, current or prior history of d-drug treatment is not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP.
- Published
- 2010
- Full Text
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100. Short-term effects of extended-release niacin on endothelial function in HIV-infected patients on stable antiretroviral therapy.
- Author
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Chow DC, Stein JH, Seto TB, Mitchell C, Sriratanaviriyakul N, Grandinetti A, Gerschenson M, Shiramizu B, Souza S, and Shikuma C
- Subjects
- Antiretroviral Therapy, Highly Active, Brachial Artery drug effects, Brachial Artery physiopathology, CD4 Lymphocyte Count, Delayed-Action Preparations pharmacology, Female, HIV Infections blood, HIV Infections physiopathology, Humans, Male, Middle Aged, Pilot Projects, Cholesterol, HDL blood, HIV Infections drug therapy, HIV-1, Hypolipidemic Agents pharmacology, Niacin pharmacology, Vasodilation drug effects
- Abstract
Objective: To assess the short-term effects of extended-release niacin (ERN) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol (HDL-c) levels., Methods: Randomized controlled study to determine the short-term effects of ERN on endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-infected adults with low HDL-c. Participants on stable HAART with fasting HDL-c less than 40 mg/dl and low-density lipoprotein-cholesterol less than 130 mg/dl were randomized to ERN or control arms. ERN treatment started at 500 mg/night and titrated to 1500 mg/night for 12 weeks. Controls received the same follow-up but were not given ERN (no placebo). Participants were excluded if they had a history of cardiac disease, uncontrolled hypertension, diabetes mellitus, or were on lipid-lowering medications such as statins and fibrates. Change in FMD was compared between arms with respect to baseline HDL-c., Results: Nineteen participants were enrolled: 89% men, median age 50 years, 53% white/non-Hispanic, median CD4 cell count 493 cells/microl, and 95% of them had HIV RNA below 50 copies/ml. Participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with -1.0 mg/dl in controls (-6.0 to 2.5), a P value is equal to 0.04. The median change in FMD was 0.91% (-2.95 to 2.21) for ERN and -0.48% (-2.65 to 0.98) for controls (P = 0.67). However, end of study FMD for ERN was significantly different from controls after adjusting for baseline differences in FMD and HDL-c, 6.36% (95% confidence interval 4.85-7.87) and 2.73% (95% confidence interval 0.95-4.51) respectively, a P value is equal to 0.048., Conclusion: This pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected patients with low HDL-c.
- Published
- 2010
- Full Text
- View/download PDF
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