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Introdução: O tratamento para toxoplasmose congênita (TC) pode cursar com supressão da medula óssea e tem potenciais efeitos como: neutropenia severa, anemia aplástica, trombocitopenia e hemólise. Desse modo, o atendimento a crianças em uso da terapia para TC na unidade de emergência deve despertar o alerta para a possibilidade de reações adversas graves. Descrição do caso: Paciente do sexo masculino, 45 dias de vida, admitido em UTI pediátrica (UTIP) com quadro de insuficiência respiratória aguda. Nos exames admissionais notou-se pancitopenia grave (hemoglobina 5,9 g/dL, leucócitos 1220/mm³e plaquetas 8.000/mm³). Na anamnese, a mãe revelou uso regular de pirimetamina, sulfadiazina e ácido folínico, em virtude do diagnóstico de TC. Nasceu a termo, sem intercorrências perinatais e na 2ªsemana de vida iniciou vômitos e convulsões, procurando o pronto-socorro diversas vezes, sem investigação da queixa. Devido à manutenção do quadro, procurou a maternidade. A análise de líquor e o ultrassom transfontanelar foram normais, sendo liberado com fenobarbital e indicação de manter as medicações para TC. Após a alta, manteve vômitos e iniciou diarreia, procurando novamente o pronto-socorro do município. Há 03 dias da admissão, evoluiu com tosse, espirros, piora dos vômitos e desconforto respiratório, sendo encaminhado para o hospital terciário da região e depois para a UTIP. Optou-se por suspender o tratamento para TC e manter suporte, tendo como hipótese diagnóstica bronquiolite associada à reação adversa grave às medicações para TC. O paciente necessitou de intubação, porém evoluiu com resposta clínica e laboratorial importantes. Durante a internação apresentou nova análise de líquor e tomografia de crânio normais e IgG para T. gondii em queda, com IgM novamente não reagente, reforçando a conduta de manter suspenso o tratamento para TC. Discussão: De acordo com os critérios de 2022 do MS, as crianças assintomáticas com IgG reagente, IgM e/ou IgA não reagentes e exame clínico, fundo de olho e USG transfontanelar normais devem repetir sorologias mensalmente e ter conduta expectante. O que chamou a atenção, neste caso, foi a indicação equivocada do tratamento, o qual levou ao desenvolvimento de reação importante, caracterizando iatrogenia. A pirimetamina inibe a atividade da diidrofolato redutase, enzima envolvida na utilização do folato para síntese de DNA. Logo, a redução dos seus níveis repercute na hematopoiese. A neutropenia acentuada gerada no paciente pode ter contribuído para a infecção clinicamente grave pelo rinovírus, uma vez que a intensidade de uma infecção também depende da imunidade do hospedeiro. Outros efeitos colaterais descritos também são compatíveis com o quadro apresentado pela criança desde o início do tratamento: vômitos, tremores e convulsões. A melhora clínica dramática após a suspensão das medicações reforça esta discussão. Conclusão: Devido à possibilidade de reações adversas graves às medicações para tratamento de TC, deve-se observar com atenção os critérios para diagnóstico e indicação de tratamento a fim de evitar iatrogenia ameaçadora de vida.

Introdução: A hemofilia A é uma das coagulopatias mais comuns e é um distúrbio genético ligado ao X que causa sangramentos importantes. A ausência de histórico familiar positivo para coagulopatias dificulta a suspeição clínica no caso índice. Assim, a busca ativa por casos com anamnese dirigida se mostra fundamental para o diagnóstico precoce e instituição de terapia em tempo hábil, evitando desfechos clínicos desfavoráveis. Descrição do caso: Paciente do sexo masculino, 1 ano, apresentou sangramento oral vultoso após realização de frenectomia. Observou-se intumescimento da musculatura da língua ocasionando exteriorização desta e ocupação de toda a cavidade oral, gerando obstrução da via aérea superior, que evoluiu com insuficiência respiratória e necessidade de Traqueostomia (TQT). Na história clínica, a mãe refere cefalo-hematoma no 1º dia de vida, evoluindo com anemia importante e necessidade de hemotransfusão na maternidade. Recebeu alta hospitalar e iniciou acompanhamento com hematopediatria, apresentando, neste período, coagulograma normal. Perdeu seguimento clínico, porém a mãe refere que o paciente apresentou equimoses espontâneas no primeiro ano de vida e teve episódio de edema importante associado a hematoma em coxa após aplicação de vacina. Negou histórico familiar de distúrbios hemostáticos. Com este quadro clínico, foi solicitado Tempo de Protrombina (TAP), Tempo de Tromboplastina Parcial Ativada (TTPA) e Tempo de Sangramento (TS). O primeiro foi normal, o segundo não foi liberado e o terceiro era alargado. Diante do quadro de sangramento, da história de apresentação e dos exames, aventou-se a hipótese de hemofilia A e iniciou-se o tratamento com plasma fresco congelado, concentrado de hemácias e de plaquetas. Antes da TQT o paciente recebeu Fator VIII recombinante e no pós-operatório, por 3 dias. A resposta clínica foi dramática, com cessação imediata do sangramento e posterior regressão do edema. Após 3 dias sem reposição, foi dosado fator VIII (5%) e fechado o diagnóstico de hemofilia A moderada. Discussão: Embora a herança genética seja ligada ao X, em cerca de 30% dos casos decorre de mutação de novo. Frente a um paciente com sangramento, não obstante a ausência de histórico familiar pertinente, deve-se ter alta suspeição para distúrbios hemostáticos, com enfoque nos mais prevalentes, como a hemofilia A, de modo que não haja atraso no diagnóstico e evolução para desfechos desfavoráveis. O quadro clínico das hemofilias é caracterizado por sangramentos em tecidos moles, músculos e articulações, além de sangramentos excessivos durante procedimentos invasivos, bem como sangramentos retardados. Crianças com hemofilia frequentemente têm sangramentos desde o período neonatal (coto umbilical, cefalo-hematoma, equimoses ao engatinhar). A rapidez em se obter o fator necessário também é fundamental para o resultado. Os critérios de inclusão para liberação de fator de reposição propostos pelo Ministério da Saúde dificultam a acessibilidade e o manejo rápido e adequado. Conclusão: Assim, é necessário educar a população acerca das coagulapatias e sobre o impacto da anamnese com busca ativa no diagnóstico precoce, mesmo quando não há herança familiar prévia. É preciso enfatizar a importância de exames pré-procedimentos contemplando coagulograma e revisar as políticas públicas sobre a distribuição de fator VIIIr nos casos suspeitos, uma vez que a resposta clínica é vultosa.

Background: A concerning increase in syphilis has been observed worldwide. Traditional surveillance is limited by the scarce routine testing of asymptomatic infections. Blood donation screening is an opportunity to monitor resolved and active syphilis infections, providing public health insights into transmission. Aims: To define syphilis prevalence, incidence and factors associated with active infection among blood donors in five Brazilian blood centers. Material and methods: Donations from Jan. 2020 through Feb. 2022 were screened with treponemal or nontreponemal tests according to the local routine assessment at each blood center, followed by a confirmatory step with an alternate Enzyme-Linked Immunosorbent Assay (ELISA) and rapid plasma reagin (RPR) testing. Samples with positive or indeterminate results in the alternate ELISA were categorized as active (if RPR reactive) or resolved syphilis (nonreactive RPR). Active cases were further categorized according to RPR titers (< 1:8 or ≥ 1:8). We report the prevalence of syphilis in first-time donations (FTD) and repeat donations (RD), incidence in RD, and use regression models to assess factors associated with active syphilis. Results: Of 862,146 donations, 10,771 (1.3%) were reactive or indeterminate on screening; 7,541 available samples underwent additional testing. Of those, 5,876 (77.9%) tested positive on the alternate ELISA; 907 (12.0%) were resolved infections, 2,980 (39.5%) were active syphilis with RPR < 1:8, and 1,989 (26.4%) were active syphilis with RPR ≥ 1:8. Overall syphilis prevalence (including resolved and active cases) was 2.5% in FTD and 0.6% in RD. The prevalence of active syphilis was 1211 and 238 per 105 donations among FTD and RD, respectively. Among FTD, the prevalence rates of active syphilis with high and low RPR titers were 466 and 745/105 donations; these rates were 4.4 and 5.6 times higher than those observed in RD. Subgroups with the highest prevalence of active syphilis were black donors (946/105 donations), donors with ≤primary education (788/105 donations) and replacement donors (822/105 donations). In the multivariable model, age, gender, race, education, donor type, and type of donation were significantly associated with active syphilis. The incidence of syphilis in RD was 90/105 person-years, with age (25-34 and ≥ 55 relative to ≤ 24 years), male gender, Black and Mixed race (relative to White), lower education, and replacement donation significantly associated with incident syphilis in RD. Discussion: We observed that both the prevalence and incidence of active syphilis are associated with male sex, black and mixed race, lower schooling, and replacement donation; compared to donors ≤ 24 years old, older donors had higher prevalence of active syphilis, whereas those aged 25-34 years old had higher incidence of syphilis. Conclusion: The prevalence of syphilis was below 3% among FTD and below 1% among RD including resolved and active cases. We found wide variation according to demographic characteristics, with age, gender, race, education, donor type, and type of donation associated with higher prevalence of active syphilis in the adjusted models. The results indicate sociodemographic subgroups that can be targeted in efforts to promote sexual health education and surveillance, prevention and control of sexually transmitted infections.

Background: Syphilis is a public health problem with traditional surveillance limited to clinical monitoring data; asymptomatic and low-risk populations rarely undergo diagnostic testing. Globally, the syphilis prevalence has consistently increased over the last years, worldwide. Blood donation screening can provide valuable information on syphilis trends over time and on the occurrence of undetected cases in the community. Aims: To evaluate the rates and the relationship between syphilis positivity in blood donors when compared against the notifications of sexually acquired syphilis, syphilis in pregnant persons, and congenital syphilis reported by the Brazilian surveillance system between 2012 and 2022. Material and methods: Data was compared directly to evaluate the correlations between deferral rates due to syphilis in first-time donors within the REDS-IV-P blood centers (per 100,000 donations); annual rates of syphilis reactivity among Brazilian blood donors obtained from the Hemotherapy Bulletin (HEMOPROD; per 100,000 donations); and rates of congenital syphilis (per 1,000 live births), sexually acquired syphilis (per 100,000 population), and syphilis in pregnant persons (per 1,000 live births) in Brazil extracted from official reports published by the Ministry of Health. The deferral rates in blood donations were based on the results of screening tests. Results: We observed an increase in syphilis detection over time by all definitions between 2012 and 2022, with a more pronounced increase in syphilis in pregnant persons (5.7x) and sexually acquired syphilis (7.0x), except for 2020, likely due to underreporting secondary to the COVID-19 pandemic. The increase in deferral rates for syphilis in blood donors in Brazil and in REDS was less sharp (1.6x and 1.4x respectively) when compared to the rates for sexually acquired syphilis and gestational syphilis. REDS-IV-P data reflected the country's deferral pattern, approximately correlating with the increase in congenital syphilis detection rates (2.5x) in the period. Discussion: There is a close correlation between syphilis rates in first-time blood donors and congenital syphilis rates recorded by the surveillance system between 2012 and 2022. Donors have lower syphilis rates than the overall adult population and a less pronounced increase in rates over time, probably due to sociodemographic and behavioral characteristics of the blood donor population.

Abstract Background It has been shown – mostly in animal models - that circadian clock genes are expressed in granulosa cells and in corpora luteum and might be essential for the ovulatory process and steroidogenesis. Objective We sought to investigate which circadian clock genes exist in human granulosa cells and whether their expression and activity decrease during aging of the ovary. Study design Human luteinized granulosa cells were isolated from young (age 18–33) and older (age 39–45) patients who underwent in-vitro fertilization treatment. Levels of clock genes expression were measured in these cells 36 h after human chorionic gonadotropin stimulation. Methods Human luteinized granulosa cells were isolated from follicular fluid during oocyte retrieval. The mRNA expression levels of the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2 were analyzed by quantitative polymerase chain reaction. Results We found that the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2, are expressed in cultured human luteinized granulosa cells. Among these genes, there was a general trend of decreased expression in cells from older women but it reached statistical significance only for PER1 and CLOCK genes (fold change of 0.27 ± 0.14; p = 0.03 and 0.29 ± 0.16; p = 0.05, respectively). Conclusions This preliminary report indicates that molecular circadian clock genes exist in human luteinized granulosa cells. There is a decreased expression of some of these genes in older women. This decline may partially explain the decreased fertility and steroidogenesis of reproductive aging.

Background: The number of revision total knee arthroplasty (TKA) has been increasing. Although many studies have analyzed the causes of revision TKA in Western countries, a limited number of studies have analyzed changes in causes of or trends in revision TKA in Asia. This study analyzed and determined the frequency and causes of failures after TKA in our hospital. We also analyzed the differences and trends over the past 17 years., Methods: A total of 296 revision TKAs performed in a single institution from 2003 to 2019 were analyzed. During the 17-year study period, patients who had undergone primary TKA between 2003 and 2011 were classified into a past group, while those who had undergone primary TKA from 2012 to 2019 were classified into a recent group. A revision performed within 2 years after primary TKA was defined as early revision. Further, differences in causes of revision TKA according to the interval from primary TKA to revision TKA were determined. The causes of revision TKA were analyzed through a comprehensive analysis of patients' medical records., Results: Overall, infection was the most common cause of failure (151/296 cases, 51.0%). Compared to the past group, the recent group had a relatively higher proportion of patients undergoing revision TKA for mechanical loosening (past group, 19.1% vs. recent group, 31.9%) and instability (11.2% vs. 13.5%) and a relatively lower proportion of patients undergoing revision TKA for infection (56.2% vs. 48.8%), polyethylene (PE) wear (9.0% vs. 2.9%), osteolysis (2.2% vs. 1.9%), and malalignment (2.2% vs. 1.0%). On comparison according to the interval from primary TKA to revision TKA, the rate of infection relatively decreased, whereas the rate of mechanical loosening and instability relatively increased in the late revision TKA compared to the early revision TKA., Conclusions: Infection and aseptic loosening were the most common reasons of revision TKA in both past and recent groups. Compared to the past, revision TKA due to PE wear has decreased significantly and revision TKA due to mechanical loosening has relatively increased recently. Orthopedic surgeons need to be aware of recent trends in mechanisms of failure and should try to recognize and address the probable causes in TKA., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

Purpose: This study aimed to investigate the effect of medial open wedge high tibial osteotomy (MOWHTO) on patellofemoral joint osteoarthritis (PF OA) progression and its outcome according to the degree of preexisting PF OA., Materials and Methods: Patients who underwent biplane MOWHTO between January 2006 and December 2018 were retrospectively reviewed. The patients were divided into two groups according to the degree of PF OA: non-PF OA [Kellgren-Lawrence (K-L) grade 0-1] and PF OA (K-L grade 2-3). Propensity score matching was performed between the two groups, and comparative analysis was performed on clinical scores and radiographic parameters and grade., Results: After propensity score matching, 83 patients were selected for each group. At postoperative follow-up, clinical scores were improved significantly compared with preoperative scores in both groups; however, there were no significant differences between the groups. There were also no significant differences between the two groups in radiographic parameters. The radiographic grade of PF OA indicated a slight progression in osteoarthritis in both groups; however, PF OA tended to progress further in the PF OA group., Conclusions: MOWHTO did not result in significant differences in outcomes at postoperative follow-up; however, preexisting PF OA contributed to PF OA progression after MOWHTO., (© 2022. The Author(s).)

Background: Residual rotational instability after isolated anterior cruciate ligament reconstruction (ACLR) has been a challenge for many years. Anterolateral extra-articular procedures (AEAPs), including anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET), are performed as a surgical option for additional rotational stability, but clear evidence for their usefulness is lacking., Purpose: To conduct a systematic review and meta-analysis of the literature regarding the efficacy of AEAP in primary ACLR., Study Design: Systematic review; Level of evidence, 3., Methods: A literature search, data extraction, and quality assessment were conducted by 2 independent reviewers. MEDLINE, EMBASE, and the Cochrane Library were searched in April 2020, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 3444 studies were screened, and 20 studies (11 randomized controlled trials and 9 nonrandomized studies) were evaluated. Functional outcomes, stability, and complications were compared between patients who underwent primary ACLR with AEAP and those who underwent isolated primary ACLR. For subgroup analysis, outcomes were compared according to AEAP technique (ALLR vs LET) and time from injury to surgery (≤12 vs >12 months). The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool, Jadad scale, and Newcastle-Ottawa Scale., Results: Compared with isolated ACLR, combined ACLR with AEAP led to improved pivot-shift grades and graft failure rates, regardless of the AEAP technique or of time from injury to surgery. A limited, marginal improvement in subjective function score was observed in patients who underwent AEAP combined with ACLR. In contrast to ALLR, patients who underwent LET combined with ACLR had an increased risk of knee stiffness and adverse events., Conclusion: Our review suggests that when there is a need to improve rotational stability and subjective function, AEAP combined with primary ACLR can be considered regardless of time from injury. ALLR appeared to be a better option for improving rotational stability compared with LET., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

Background: The best treatment for degenerative medial meniscus posterior root tear (MMPRT) remains controversial. This study aimed to compare the clinical and radiological outcomes of arthroscopic meniscectomy and conservative treatment for degenerative MMPRT., Methods: From January 2007 to December 2014, 146 patients (Meniscectomy group, 90; Conservative group, 56) were evaluated. Clinical outcomes were assessed using the Visual Analog Scale, International Knee Documentation Committee subjective scoring scale, Tegner activity scale, and Lysholm knee scoring scale at the final follow-up. Radiologic outcomes evaluated the progression of osteoarthritis (OA) according to the Kellgren-Lawrence (K-L) classification. We compared the hip-knee-ankle angle (HKAA), medial proximal tibial angle, tibial posterior slope angle, and width of medial joint space. After an average follow-up of 6.3 years, the survivorship was analyzed using the Kaplan-Meier method., Results: All clinical outcomes were significantly improved in both groups after treatment, with no significant differences between the two groups at the final follow-up. The progression of OA according to the K-L classification, HKAA and width of medial joint space was significantly advanced in the meniscectomy group (p = 0.03, 0.04, 0.03, respectively). The 10-year survival rates in the meniscectomy and conservative groups were 87 and 88%, respectively., Conclusions: This study demonstrated that both conservative treatment and meniscectomy provided symptomatic relief. However, it was confirmed that OA progression was more severe in the meniscectomy. We conclude that arthroscopic meniscectomy had no advantage over conservative treatment in terms of clinical outcomes and OA progression in middle-aged patients with MMPRT., Level of Evidence: Level III; retrospective comparative study., (© 2021. The Author(s).)

The cervical spine can be injured even in the absence of radiographic abnormality, and the best surgical treatment for adult spinal cord injury without bone injury is debated. The aim of this study was to retrospectively investigate the effect of surgical decompression for severe adult spinal cord injury without major bone injury and to establish predictors of good neurological outcome. We analyzed 11 patients who underwent surgical decompression in severe adult spinal cord injury without major bone injury patients classified as American Spinal Injury Association Impairment Scale (AIS) grade A, B, or C. Neurological assessments were performed using AIS at preoperative and postoperative 1-year follow-up. Radiological evaluations were performed using cervical magnetic resonance imaging (MRI) at preoperative. Seven cases were classified as AIS grade A; two cases as AIS grade B; and two cases as AIS grade C. Five of 11 (45.5%) patients showed improved neurological grade 1-year postoperatively. Intramedullary lesion length (IMLL) ( p = 0.047) and compression rate ( p = 0.045) had the most powerful effect on AIS grade conversion. This study shows that the fate of the injured spinal cord is determined at the time of the injury, but adequate decompression may have limited contribution to the recovery of neurological function. Compression rate and IMLL on MRI can be used as a predictor of neurological recovery.

The digestion rates of microalgal (docosahexaenoic acid, DHA, 56.8%; palmitic acid, 22.4%), fish (DHA, 10.8%; eicosapentaenoic acid, EPA, 16.2%), and soybean oils (oleic, 21.7%; linoleic acid, 54.6%) were compared by coupling the in vitro multi-step and in vivo apparent digestion models using mice. The in vitro digestion rate estimated based on the released free fatty acids content was remarkably higher in soybean and fish oils than in microalgal oil in 30 min; however, microalgal and fish oils had similar digestion rates at longer digestion. The in vivo digestibility of microalgal oil (91.49%) was lower than those of soybean (96.50%) and fish oils (96.99%). Among the constituent fatty acids of the diet oils, docosapentaenoic acid (DPA) exhibited the highest digestibility, followed by EPA, DHA, palmitoleic, oleic, palmitic, and stearic acid, demonstrating increased digestibility with reduced chain length and increased unsaturation degree of fatty acid. The diet oils affected the deposition of fatty acids in mouse tissues, and DHA concentrations were high in epididymal fat, liver, and brain of mice fed microalgal oil. In the present study, microalgal oil showed lower in vitro and in vivo digestibility, despite adequate DHA incorporation into major mouse organs, such as the brain and liver.

Competing Interests: No potential conflicts of interest relevant to this article were reported.

Correct temporal and spatial control of actin dynamics is essential for the cytotoxic T cell effector function against tumor cells. However, little is known whether actin engineering in tumor-targeted T cells can enhance their antitumor responses, thereby potentiating the adoptive T cell therapy. Here, we report that TAGLN2, a 22-KDa actin-stabilizing protein which is physically associated with lymphocyte function-associated antigen-1 (LFA-1), potentiates the OTI TCR CD8 + T cells to kill the intercellular adhesion molecule-1 (ICAM-1)-positive/OVA-presenting E0771 cells, but not ICAM-1-negative OVA-B16F10 cells, suggesting an 'inside-out' activation of LFA-1, which causes more efficient immunological synapse formation between T cells and tumor cells. Notably, recombinant TAGLN2 fused with the protein transduction domain (TG2P) overcame the disadvantages of viral gene delivery, leading to a significant reduction in tumor growth in mice. TG2P also potentiated the CD19-targeted, chimeric antigen receptor (CAR)-modified T cells to kill Raji B-lymphoma cells. Our findings indicate that activating the TAGLN2-actin-LFA-1 axis is an effective strategy to potentiate the adoptive T-cell immunotherapy.

Background: Mitochondrial DNA (mtDNA) mutations may regulate the progression and chemosensitivity of leukemia. Few studies regarding mitochondrial aberrations and haplogroups in acute myeloid leukemia (AML) and their clinical impacts have been reported. Therefore, we focused on the mtDNA length heteroplasmies minisatellite instability (MSI), copy number alterations, and distribution of mitochondrial haplogroups in Korean patients with AML., Methods: This study investigated 74 adult patients with AML and 70 controls to evaluate mtDNA sequence alterations, MSI, mtDNA copy number, haplogroups, and their clinical implications. The hypervariable (HV) control regions ( HV1 and HV2 ), tRNA leu1 gene, and cytochrome b gene of mtDNA were analyzed. Two mtDNA minisatellite markers, 16189 poly-C ( 16184 CCCCCTCCCC 16193 , 5CT4C) and 303 poly-C ( 303 CCCCCCCTCCCCC 315 , 7CT5C), were used to examine the mtDNA MSI., Results: In AML, most mtDNA sequence variants were single nucleotide substitutions, but there were no significant differences compared to those in controls. The number of mtMSI patterns increased in AML. The mean mtDNA copy number of AML patients increased approximately 9-fold compared to that of controls ( P <0.0001). Haplogroup D4 was found in AML with a higher frequency compared to that in controls (31.0% vs. 15.7%, P =0.046). None of the aforementioned factors showed significant impacts on the outcomes., Conclusion: AML cells disclosed more heterogeneous patterns with the mtMSI markers and had increased mtDNA copy numbers. These findings implicate mitochondrial genome instability in primary AML cells. Therefore, mtDNA haplogroup D4 might be associated with AML risk among Koreans., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

TAGLN is an actin-binding protein family that comprises three isoforms with theorized roles in smooth muscle differentiation, tumour development, lymphocyte activation, and brain chemistry. However, their fundamental characteristics in regulation of the actin-based cytoskeleton are not fully understood. Here we show that TAGLN2 (including TAGLN1 and TAGLN3) extensively nucleates G-actin polymerization under low-salt conditions, where polymerization would be completely suppressed. The calponin homology domain and actin-binding loop are essential to mechanically connect two adjacent G-actins, thereby mediating multimeric interactions. However, TAGLN2 blocked the Arp2/3 complex binding to actin filaments under physiological salt conditions, thereby inhibiting branched actin nucleation. In HeLa and T cells, TAGLN2 enhanced filopodium-like membrane protrusion. Collectively, the dual functional nature of TAGLN2-G-actin polymerization and Arp2/3 complex inhibition-may account for the mechanisms of filopodia development at the edge of Arp2/3-rich lamellipodia in various cell types.

The immunological synapse (IS), a dynamic and organized junction between T-cells and antigen presenting cells (APCs), is critical for initiating adaptive immunity. The actin cytoskeleton plays a major role in T-cell reorganization during IS formation, and we previously reported that transgelin-2, an actin-binding protein expressed in T-cells, stabilizes cortical F-actin, promoting T-cell activation in response to antigen stimulation. Transgelin-2 is also highly expressed in B-cells, although no specific function has been reported. In this study, we found that deficiency in transgelin-2 (TAGLN2-/-) in B-cells had little effect on B-cell development and activation, as measured by the expression of CD69, MHC class II molecules, and CD80/86. Nevertheless, in B-cells, transgelin-2 accumulated in the IS during the interaction with T-cells. These results led us to hypothesize that transgelin-2 may also be involved in IS stability in B-cells, thereby influencing T-cell function. Notably, we found that transgelin-2 deficiency in B-cells reduced T-cell activation, as determined by the release of IL-2 and interferon-γ and the expression of CD69. Furthermore, the reduced T-cell activation was correlated with reduced B-cell-T-cell conjugate formation. Collectively, these results suggest that actin stability in B-cells during IS formation is critical for the initiation of adaptive T-cell immunity.

Nuclear speckles are subnuclear storage sites containing pre-mRNA splicing machinery. Proteins assembled in nuclear speckles are known to modulate transcription and pre-mRNA processing. We have previously identified nuclear speckle-related protein 70 (NSrp70) as a novel serine/arginine (SR)-related protein that co-localizes with classical SR proteins such as serine/arginine-rich splicing factor 1 (SRSF1 or ASF/SF2) and SRSF2 (SC35). NSrp70 mediates alternative splice site selection, targeting several pre-mRNAs, including CD44 exon v5. Here we demonstrated that NSrp70 interacts physically with two SR proteins, SRSF1 and SRSF2, and reverses their splicing activity in terms of CD44 exon v5 as exon exclusion. The NSrp70 RS-like region was subdivided into three areas. Deletion of the first arginine/serine-rich-like region (RS1) completely abrogated binding to the SR proteins and to target mRNA and also failed to induce splicing of CD44 exon v5, suggesting that RS1 is critical for NSrp70 functioning. Interestingly, RS1 deletion also resulted in the loss of NSrp70 and SR protein speckle positioning, implying a potential scaffolding role for NSrp70 in nuclear speckles. NSrp70 contains an N-terminal coiled-coil domain that is critical not only for self-oligomerization but also for splicing activity. Consistently, deletion of the coiled-coil domain resulted in indefinite formation of nuclear speckles. Collectively, these results demonstrate that NSrp70 acts as a new molecular counterpart for alternative splicing of target RNA, counteracting SRSF1 and SRSF2 splicing activity., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Atopic dermatitis (AD) is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA) isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production.

Background: Unicompartmental knee arthroplasty(UKA) has become a treatment of choice for many patients with isolated unicomparmental arthritis due to its specific advantages over total knee arthroplasty, but few studies have compared conventional and navigational UKA with similar instrumentation on mid- to long-term results. We investigated whether the use of imageless navigation can improve implant positioning and clinical outcomes of UKA at a long-term follow-up compared to the conventional technique., Methods: We prospectively studied clinical and radiological results in 68 patients with an average age of 64.0 years (range, 50 to 81 years) who received UKA between January 2003 and December 2005 using the conventional or navigational technique. Clinical evaluations were performed preoperatively and the last follow-up included knee range of motion, Hospital for Special Surgery (HSS) scores, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and Visual Analogue Scale (VAS) pain score. For radiologic evaluation, the mechanical alignment of the lower limb was measured using mechanical femoro-tibial angle (mFTA) and Kennedy protocol., Results: After an average 9-year follow-up (range, 7.4 to 10.8 years), the navigation group showed better coronal alignments of the components, fewer radiological outliers and better clinical scores, but similar estimated 10-year prosthesis survival rates., Conclusion: This study indicates that the use of navigation significantly contributes to the desired mechanical axis and improved component placement as compared to the conventional technique., Level of Evidence: Prospective comparative study, Level III., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a skin condition caused by an imbalance of distinct subsets of T helper cells. Previously, we showed that 4-hydroxy-3-methoxycinnamaldehyde (4H3MC) inhibits T cell activation but does not induce apoptosis. Here, we examined the mechanism underlying the inhibitory effect of 4H3MC on AD both in vivo and in vitro. We sought to test the pharmacological effects of 4H3MC using a mouse model of 2, 4-'2,4-dinitrocholorobenzene' (DNCB)- and mite-induced AD. Also, we determined whether 4H3MC affects T cell differentiation and proliferation. Oral administration of 4H3MC attenuated the symptoms of DNCB- and mite-induced AD, including increased ear thickness, serum IgE levels, immune cell infiltration into inflammatory lesions, and pathogenic cytokine expression in ear tissues. In vitro, 4H3MC blocked T cell differentiation into Th1 and Th2 subtypes, as reflected by suppression of T-bet and GATA3, which are key transcription factors involved in T cell differentiation. In addition, 4H3MC downregulated T cell proliferation during Th1 and Th2 differentiation and keratinocyte activation. Collectively, these findings suggest that 4H3MC ameliorates AD symptoms by modulating the functions of effector T cells and keratinocytes.

Actin dynamics is critical for the formation and sustainment of the immunological synapse (IS) during T cell interaction with antigen-presenting cells (APC). Thus, many actin regulating proteins are involved in spatial and temporal actin remodeling at the IS. However, little is known whether or how actin stabilizing protein controls IS and the consequent T cell functions. TAGLN2 - an actin-binding protein predominantly expressed in T cells - displays a novel function to stabilize cortical F-actin, thereby augmenting F-actin contents at the IS, and acquiring leukocyte function-associated antigen-1 activation following T cell activation. TAGLN2 also competes with cofilin to protect F-actin in vitro and in vivo. During cytotoxic T cell interaction with cancer cells, the expression level of TAGLN2 at the IS correlates with the T cell adhesion to target cancer cells and production of lytic granules such as granzyme B and perforin, thus expressing cytotoxic T cell function. These findings identify a novel function for TAGLN2 as an actin stabilizing protein that is essential for stable immunological synapse formation, thereby regulating T cell immunity.

Background: In this work, we present relatively long-term results of femoral head fractures with a specific focus on Pipkin type I fractures., Methods: Fifty-nine femoral head fractures were treated according to modified Pipkin's classification as follows: type I, small fragment distal to the fovea centralis (FC); type II, large fragment distal to the FC; type III, large fragment proximal to the FC; type IV, comminuted fracture. There were 15 cases of type I, 28 of type II, 9 of type III, and 7 of type IV fractures. Conservative treatment with skeletal traction was performed in 4 type II cases, excision of the fragment in 15 type I and 10 type II cases, fixation of the fragment in 14 type II and all 9 type III cases, and total hip replacement in all 7 type IV cases. The overall clinical and radiographic outcomes were evaluated using previously published criteria, focusing on the results in Pipkin type I fractures with relatively large fragments., Results: Based on Epstein criteria, in type II fractures, excellent or good clinical results were seen in 6 of 10 patients (60.0 %) treated by excision of the fragment and 12 of 14 patients (85.7 %) treated by internal fixation (p = 0.05). Also, excellent or good radiologic results were seen in 4 of 10 (40.0 %) patients treated by excision of the fragment and 12 of 14 (85.7 %) patients treated by internal fixation (p = 0.03)., Conclusions: Even in Pipkin type I fractures, if the fragment is large (modified Pipkin type II), early reduction and internal fixation can produce good results.

Background: The aim of this study was to assess the results of using the Ilizarov apparatus to transport bones in the treatment of benign bone tumors., Methods: Seven patients (six males and one female) with benign bone tumors were treated by bone transport with an Ilizarov apparatus at our institution. Their mean age at surgery was 14.4 years (range, 4.8 to 36.9 years). The histological diagnoses were osteofibrous dysplasia (4), giant-cell tumor (1), intraosseous cavernous hemangioma (1), and aneurysmal bone cyst (1). Three radiological indices were used for evaluating the results: an external fixation index, a distraction index, and a maturation index. The bone and functional results were evaluated according to the Association for the Study and Application of the Method of Ilizarov classification., Results: Five patients had bone union at the reconstructed site, one patient had a local recurrence, and the other had a nonunion at the docking site. The mean length of distraction was 7.3 cm (range, 5.1 to 12.1 cm). The mean external fixation index was 26.0 day/cm (range, 19.8 to 32.5 day/cm), the distraction index was 9.6 day/cm (range, 6.8 to 12.0 day/cm), and the maturation index was 14.9 day/cm (range, 8.0 to 22.5 day/cm). Ultimately, the bone and the functional results were rated excellent in six cases and good in one case., Conclusions: Bone transport using the Ilizarov apparatus is a good treatment option in patients with bone defects after the resection of an active or aggressive benign bone tumor.

The formation of an immunological synapse (IS) requires tight regulation of actin dynamics by many actin polymerizing/depolymerizing proteins. However, the significance of actin stabilization at the IS remains largely unknown. In this paper, we identify a novel function of TAGLN2--an actin-binding protein predominantly expressed in T cells--in stabilizing cortical F-actin, thereby maintaining F-actin contents at the IS and acquiring LFA-1 (leukocyte function-associated antigen-1) activation after T cell receptor stimulation. TAGLN2 blocks actin depolymerization and competes with cofilin both in vitro and in vivo. Knockout of TAGLN2 (TAGLN2(-/-)) reduced F-actin content and destabilized F-actin ring formation, resulting in decreased cell adhesion and spreading. TAGLN2(-/-) T cells displayed weakened cytokine production and cytotoxic effector function. These findings reveal a novel function of TAGLN2 in enhancing T cell responses by controlling actin stability at the IS., (© 2015 Na et al.)

Autoreactive T-cell responses have a crucial role in the pathology and clinical course of autoimmune diseases. Therefore, controlling the activation of these cells is an important strategy for developing therapies and therapeutics. Here, we identified that 4-hydroxy-3-methoxycinnamaldehyde (4H3MC) has a therapeutic potential for T-cell activation by modulating protein kinase C-θ (PKCθ) and its downstream pathways. Pre- and post-treatment with 4H3MC prevented IL-2 release from human transformed and untransformed T cells at the micromolar concentrations without any cytotoxic effects, in fact more efficiently than its structural analogue 4-hydroxycinnamic acid-a previously reported T-cell inhibitor. In silico analysis showed that 4H3MC is a potential inhibitor of PKC isotypes, including PKCθ-a crucial PKC isotype in T cells. Consistently, 4H3MC significantly blocked PKC activity in vitro and also inhibited the phosphorylation of PKCθ in T cells. 4H3MC had no effect on TCR-mediated membrane-proximal-signalling events such as phosphorylation of Zap70. Instead, it attenuated the phosphorylation of mitogen-activated protein kinases (ERK and p38) and promoter activities of NF-κB, AP-1 and NFAT. Taken together, our results provide the evidences that 4H3MC may have curative potential as a novel immune modulator in a broad range of immunopathological disorders by modulating PKCθ activity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aplotaxene, (8Z, 11Z, 14Z)-heptadeca-1, 8, 11, 14-tetraene, is one of the major components of essential oil obtained from Inula helenium root, which is used in Oriental medicine. However, the effects of aplotaxene on immunity have not been investigated. Here, we show that aplotaxene inhibits T cell activation in terms of IL-2 and CD69 expression. Aplotaxene, at a concentration that optimally inhibits IL-2 production, has little effect on apoptotic or necrotic cell death, suggesting that apoptosis is not a mechanism for aplotaxene-mediated inhibition of T cell activation. Aplotaxene affects neither superantigeninduced conjugate formation between Jurkat T cells and Raji B cells nor clustering of CD3 and LFA-1 at the immunological synapse. Aplotaxene significantly inhibits PKC-θ phosphorylation and translocation to the immunological synapse, and blocks PMA-induced T-cell receptor internalization. Furthermore, aplotaxene leads to inhibition of mitogen-activated protein kinases (JNK, ERK and p38) phosphorylation and NF-κB, NF-AT, and AP-1 promoter activities in Jurkat T cells. Taken together, our findings provide evidence for the immunosuppressive effect of aplotaxene on activated T cells through the modulation of the PKC-θ and MAPK pathways, suggesting that aplotaxene may be a novel immunotherapeutic agent for immunological diseases related to the overactivation of T cells., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Protein functions are often revealed by their localization to specialized cellular sites. Recent reports demonstrated that swiprosin-1 is found together with actin and actin-binding proteins in the cytoskeleton fraction of human mast cells and NK-like cells. However, direct evidence of whether swiprosin-1 regulates actin dynamics is currently lacking. We found that swiprosin-1 localizes to microvilli-like membrane protrusions and lamellipodia and exhibits actin-binding activity. Overexpression of swiprosin-1 enhanced lamellipodia formation and cell spreading. In contrast, swiprosin-1 knockdown showed reduced cell spreading and migration. Swiprosin-1 induced actin bundling in the presence of Ca(2+), and deletion of the EF-hand motifs partially reduced bundling activity. Swiprosin-1 dimerized in the presence of Ca(2+) via its coiled-coil domain, and a lysine (Lys)-rich region in the coiled-coil domain was essential for regulation of actin bundling. Consistent with these observations, mutations of the EF-hand motifs and coiled-coil region significantly reduced cell spreading and lamellipodia formation. We provide new evidence of how swiprosin-1 influences cytoskeleton reorganization and cell spreading.

Background: A number of different nasal packing materials are available for prevention of nasal bleeding after endoscopic sinus surgery. Polyvinyl alcohol (PVA) coated nasal packing is an expandable packing for use in rhinological surgery. This innovative surf- ace treatment helps to reduce the possibility of adherence to tissue and of blood clotting within the sponge. The present study investigated the effects of PVA coated packing and non-absorbable packing with respect to pain, healing site and postoperative bleeding following endoscopic sinus surgery., Methodology: Patients between 18-80 years of age undergoing sinus surgery were enrolled. Each patient`s ethmoid cavities were randomised to receive PVA coated packing material or the standard non-absorbable sinus packs. The remaining nasal packing material was removed on the 2nd day in the clinic. We determined visual analog scale score, bleeding time and wound healing status. A single rhinologist graded postoperative endoscopic appearance. Length of follow-up was 3 months., Results: Thirty three patients were recruited. There was a significant difference in the bleeding time between the two groups, but pain and wound healing were not significantly different between the two groups., Conclusion: PVA-coated nasal packing presents comparable characteristics with traditional nasal packing.

Swiprosin-1 exhibits the highest expression in CD8(+) T cells and immature B cells and has been proposed to play a role in lymphocyte biology through actin remodeling. However, regulation of swiprosin-1 gene expression is poorly understood. Here we report that swiprosin-1 is up-regulated in T cells by PKC pathway. Targeted inhibition of the specific protein kinase C (PKC) isotypes by siRNA revealed that PKC-θ is involved in the expression of swiprosin-1 in the human T cells. In contrast, down-regulation of swiprosin-1 by A23187 or ionomycin suggests that calcium-signaling plays a negative role. Interestingly, swiprosin-1 expression is only reduced by treatment with NF-κB inhibitors but not by NF-AT inhibitor, suggesting that the NF-κB pathway is critical for regulation of swiprosin-1 expression. Collectively, these results suggest that swiprosin-1 is a PKC-θ-inducible gene and that it may modulate the late phase of T cell activation after antigen challenge.

Sudden sensorineural hearing loss with vertigo (SSNHL&#95;V) and vestibular neuritis (VN) are common neuro-otologic disorders that cause acute spontaneous vertigo. The SSNHL&#95;V and VN lesion sites are thought to be within the labyrinth and the vestibular nerve, respectively. Neurolabyrinthitis of a viral origin is the most commonly accepted etiology of SSNHL&#95;V, and neural degeneration due to viral infection (predominantly in the superior vestibular nerve) is thought to be responsible for the pathophysiology of VN. The objective of this study was to compare the static vestibular imbalance between SSNHL&#95;V and VN patients during the acute stage of the disease. We compared the results of spontaneous nystagmus (SN), subjective visual vertical (SVV), and canal paresis (CP) between SSNHL&#95;V and VN patients within 10 days from the onset of vertigo. Significant SN was observed in 58% of SSNHL&#95;V and 90% of VN patients (p < 0.001), and abnormal SVV was observed in 10% of SSNHL&#95;V and 78% of VN patients (p < 0.001). However, CP values were not significantly different between the 2 groups (50.8 ± 19.7% in SSNHL&#95;V and 57.1 ± 18.9% in VN). In conclusion, significant SN and abnormal SVV are less frequently encountered in SSNHL&#95;V than in VN even though the caloric test did not reveal significant differences at the acute stage., (Copyright © 2013 S. Karger AG, Basel.)

T lymphocytes (T cells) circulate from the blood into secondary lymphoid organs for immune surveillance. In this study, we hypothesized that circulating T cells are heterogeneous and can be grouped according to their differential migratory capacity in response to chemoattractants, rather than expressions of certain receptors or cytokines. We further hypothesized that, at least in part, this intrinsic difference in motility may be related to the T cell function. We established motile (m-T) and non-motile T (nm-T) cell lines based on their response to the chemokine SDF-1α. m-T cells showed more irregular and polarized morphologies than nm-T cells did. Interestingly, m-T cells produced higher levels of IL-2, a marker for T cell activation, than nm-T cells did after stimulation; however, no differences were observed in terms of surface expression of T cell receptors (TCR), adhesion molecules LFA-1 and ICAM-1, and chemokine receptor CXCR4. Both cell lines also showed similar membrane events (i.e., T cell-APC conjugation, LFA-1 accumulation at the immunological synapse, and TCR internalization). In contrast, PKC-θ, a downstream of PI3K-Akt pathway was constitutively activated in m-T cells and the activation was more prominent during T cell stimulation. Consequently, NF-κB activity was selectively upregulated in m-T cells. This study is the first, to our knowledge, to demonstrate that T cells can be subcategorized on the basis of their intrinsic migratory capacity in relation to T cell activation.

The phytocomponent p-hydoxycinnamic acid (HCA) has been shown to have many beneficial effects in terms of antioxidant activity, inhibition of melanogenesis, bone resorption, and platelet activity, and stimulation of mineralization. However, effects of HCA in immune functions have not been investigated. Here, we show that HCA has a profound effect on IL-2 production in Jurkat T cells as well as in human peripheral blood leukocytes. HCA, at a concentration that optimally inhibits IL-2 production, had little effect on apoptotic or necrotic cell death of Jurkat T cells, suggesting that apoptosis is not a mechanism for HCA-induced T-cell suppression. On the contrary, HCA dramatically inhibited PKC-θ accumulation and further phosphorylation at the immunological synapse which formed at the contact site between T cells and superantigen SEE-loaded antigen presenting cells. In addition, HCA significantly inhibited ERK and p38 kinase phosphorylation in both anti-CD3/28- and PMA/A23187-stimulated T cells. Consequently, HCA inhibited both AP-1 and NF-κB promoter activities in Jurkat T cells. Collectively, our results provide evidence for the immunosuppressive effect of HCA on activated T cells, through modulation of PKC-θ pathway., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Although biphasic head-shaking nystagmus (HSN) is a basic response to head shaking in patients with unilateral vestibular loss, monophasic HSN is commonly seen in patients with dizziness of undetermined etiology. Since the clinical significance of HSN remains unclear, we sought to characterize different types of HSN in patients with vestibular neuritis (VN) during the acute stage (within 7 days after the onset of vertigo) and at follow-up (about 2 months after the onset of vertigo), and to compare HSN and caloric responses. We analyzed HSN, spontaneous nystagmus and caloric tests in 66 patients with VN. Overall, HSN showed high abnormal rates (94 and 89%) during the acute and follow-up stages and could detect vestibular hypofunction even when canal paresis (CP) had normalized at follow-up. All patients in the acute stage and most patients at follow-up showed HSN with the slow phase to the lesioned side (paretic). Biphasic HSN was common at follow-up, and many patients with a monophasic paretic pattern during the acute stage had evolved to a biphasic paretic pattern at follow-up. Initial slow-phase eye velocities (SPVs) in biphasic HSN were larger than those in monophasic HSN at follow-up. Absence of HSN or reversal of its direction was closely related to normalized caloric responses, but SPVs of HSN did not correlate with the severity of CP. These findings indicate that the HSN test is a sensitive detector of vestibular hypofunction upon 2-Hz head rotation. HSN may reveal previous vestibular hypofunction in the 2-Hz frequency range even at follow-up, when caloric responses detecting vestibular hypofunction in the low-frequency range had normalized. The two tests utilize different mechanisms to assess vestibular hypofunction and are complementary. Biphasic paretic HSN is the most common pattern at follow-up and occurs when the initial SPVs induced by head rotation are large enough to induce the adaptation of primary vestibular afferent activity. Monophasic HSN, which is commonly found in dizzy patients, indicates less severe vestibular hypofunction than biphasic HSN in the 2-Hz frequency range, and the caloric tests can provide further information about the side and presence of vestibular hypofunction at lower frequencies., (Copyright © 2012 S. Karger AG, Basel.)

Dimeric intercellular adhesion molecule-1 (ICAM-1) has been known to more efficiently mediate cell adhesion than monomeric ICAM-1. Here, we found that truncation of the intracellular domain of ICAM-1 significantly enhances surface dimerization based on the two criteria: 1) the binding degree of monomer-specific antibody CA-7 and 2) the ratio of dimer/monomer when a mutation (L42→C42) was introduced in the interface of domain 1. Mutation analysis revealed that the positively charged amino acids, including very membrane-proximal ⁵⁰⁵R, are essential for maintaining the structural transition between the monomer and dimer. Despite a strong dimer presentation, the ICAM-1 mutants lacking an intracellular domain (IC1ΔCTD) or containing R to A substitution in position 505 (⁵⁰⁵R/A) supported a lower degree of cell adhesion than did wild-type ICAM-1. Collectively, these results demonstrate that the native structure of surface ICAM-1 is not a dimer, but is an intermediate monomer-dimer equilibrium structure by which the effectiveness of ICAM-1 can be fully achieved., (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)

Objective: Our purposes were to characterize hyperventilation-induced nystagmus (HVIN) in patients with unilateral vestibular neuritis (VN) through follow-up examinations and to determine the effects of hyperventilation on vestibular imbalance in patients with VN., Materials and Methods: The horizontal eye movements in 35 patients with acute VN were recorded. The eye movements were analyzed and the maximum value of slow-phase eye velocity (SPV) was obtained during and after hyperventilation. Nineteen of 35 patients underwent follow-up examinations around 7 weeks later. When spontaneous nystagmus was present, the SPV of spontaneous nystagmus was subtracted from that of HVIN. A maximum SPV of HVIN of ≥4°/s was considered abnormal. The direction and SPV of HVIN were analyzed., Results: The incidence of HVIN in patients with VN was significantly higher in the acute stage (18 of 35; 51%) than the follow-up stage (4 of 19; 21%). The direction of HVIN present in the follow-up stage was entirely towards the contralesional side (contralesional HVIN). However, the direction of HVIN in the acute stage was mixed, towards the contralesional side (10 of 35; 28%) and towards the ipsilesional side (8 of 35; 23%). The SPVs (49 ± 56°/s) of ipsilesional HVIN were significantly greater than the contralesional HVIN in the acute stage (8 ± 3°/s). Robust nystagmus (SPV ≥ 25°/s) was entirely ipsilesional HVIN, which was observed only in the acute stage., Conclusions: Our findings indicate that hyperventilation can result in aggravation of vestibular imbalance in the acute and follow-up stages in different ways. Hyperventilation resulted in contralesional HVIN in both the acute and follow-up stages, each in approximately a fourth of the patients, which suggests a disruption of central static compensatory mechanisms. However, ipsilesional HVIN was elicited only in the acute stage (in approximately a fourth of the patients). About half of the patients with ipsilesional HVIN showed robust responses, which is a characteristic finding, suggesting a transient intense increase in vestibular activity on the lesional side., (Copyright © 2010 S. Karger AG, Basel.)

Purpose: The formulated ethanol extract (DA-9601) of Artemisia asiatica has pronounced antiinflammatory activities and exhibits cytoprotective effects against gastrointestinal damage. Here we investigated whether eupatilin, a major component of DA-9601, has a property of antioxidant activity and protects gastric epithelial cells from H2O2-induced damage. Methods., Methods: epithelial AGS cells by measuring wound healing, cell proliferation, and cell viability. Global gene expression profiling was obtained by high-density microarray., Results: Hydrogen peroxide significantly delayed epithelial migration in wounded area. In contrast, eupatilin prevented the reduction of epithelial migration induced by H2O2. Eupatilin also ameliorated H2O2-induced actin disruption in AGS cells. Interestingly, treatment with eupatilin dramatically inhibited FeSO4-induced ROS production in a dose-dependent manner. In addition, eupatilin protected cells from FeSO4-induced F-actin disruption. With high-density microarray, we identified dozens of genes whose expressions were up-regulated in H2O2-treated cells. We found that eupatilin reduces the expression of such oxidative-responsible genes as HO-1, PLAUR and TNFRSF10A in H2O2-treated cells., Conclusion: These results suggest that eupatilin acts as a novel antioxidant and may play an important role in DA-9601-mediated effective repair of the gastric mucosa.

No direct evidence has been reported whether the spatial organization of ICAM-1 on the cell surface is linked to its physiological function in terms of leukocyte adhesion and transendothelial migration (TEM). Here we observed that ICAM-1 by itself directly regulates the de novo elongation of microvilli and is thereby clustered on the microvilli. However, truncation of the intracellular domain resulted in uniform cell surface distribution of ICAM-1. Mutation analysis revealed that the C-terminal 21 amino acids are dispensable, whereas a segment of 5 amino acids ((507)RKIKK(511)) in the NH-terminal third of intracellular domain, is required for the proper localization and dynamic distribution of ICAM-1 and the association of ICAM-1 with F-actin, ezrin, and moesin. Importantly, deletion of the (507)RKIKK(511) significantly delayed the LFA-1-dependent membrane projection and decreased leukocyte adhesion and subsequent TEM. Endothelial cells treated with cell-permeant penetratin-ICAM-1 peptides comprising ICAM-1 RKIKK sequences inhibited leukocyte TEM. Collectively, these findings demonstrate that (507)RKIKK(511) is an essential motif for the microvillus ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.