48 results on '"Syed Haq"'
Search Results
2. Pseudocirrhosis in Metastatic Breast Cancer in a Male Successfully Treated with Leuprorelin and Anastrozole Followed by Eribulin: A Case Report
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Hafez Golzarian, Morgan Turnow DO, Alaha Mariam, Sidra Shah DO, Syed Haq DO, Christopher Hawkins, Benjamin Pasley, Joseph Sree, and Rajpal Aujla
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BackgroundThere are very few studies and cases in the literature describing metastatic breast cancer in the male population, accounting for less than 1% of all cases. Of those who have been reported, the vast majority fail to survive beyond 5 years from time of diagnosis. The lack of literature in this population makes it difficult for clinicians to foresee and prepare for upcoming complications in management. One of the more serious complications in managing metastatic breast cancer is the development of pseudocirrhosis, a frequent long-term side effect of chemotherapy and/or radiation typically seen in patients with malignancy in the liver.Case PresentationWe report the case of a 48-year-old male with a completely unremarkable family, medical, and social history other than a homozygous mutation in his MTHFR gene who was diagnosed with stage IV ER/PR-positive, HER-2/neu negative, BRCA1 and BRCA2-negative breast cancer with metastasis to bone, lung, and liver who was successfully treated with a regimen consisting of radiation, Denosumab, Leuprorelin, and Anastrozole. 8 years later since initiation of treatments, he continues to survive and undergo symptomatic management of long-term side-effects of his treatments.ConclusionsTo our knowledge this is the only reported case of metastatic breast cancer with pseudocirrhosis in a male patient. It is imperative to report this unique case to help increase awareness for clinicians managing other males with breast cancer. What makes this case even more reportable is the good outcome overall as our patient remains alive and well 8 years since time of diagnosis, a relatively difficult and rare feat to achieve in end-stage breast cancer.
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- 2022
3. Pseudocirrhosis in Metastatic Breast Cancer in a Male Successfully Treated with Leuprorelin and Anastrozole Followed by Eribulin: A Case Report
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Golzarian, Hafez, primary, DO, Morgan Turnow, additional, Mariam, Alaha, additional, DO, Sidra Shah, additional, DO, Syed Haq, additional, Hawkins, Christopher, additional, Pasley, Benjamin, additional, Sree, Joseph, additional, and Aujla, Rajpal, additional
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- 2022
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4. Coccidioidomycosis Resulting in a Prosthetic Joint Infection in an Immunocompetent Patient after a Total Hip Arthroplasty: A Case Report and Review of the Literature
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Suresh J. Antony, Syed Haq, and Sidra Shah
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Microbiology (medical) ,Pharmacology ,medicine.medical_specialty ,Coccidiomycosis ,business.industry ,Prosthetic joint infection ,General Medicine ,Surgery ,medicine ,Molecular Medicine ,In patient ,Presentation (obstetrics) ,business ,Total hip arthroplasty - Abstract
Abstract:: Coccidioidomycosis is a fungal infection that is a rare cause of prosthetic joint infection (PJI) in patients. This case report describes an immunocompetent patient who had a right total hip arthroplasty (THA) complicated with Coccidioidomycosis. This patient is the 9th reported case of Coccidioidomycosis, causing a PJI and only the second case to be reported in a THA. Once progressed, it can be difficult to treat, often reoccurring and requiring repeat surgical and prolonged therapy. This study discusses the clinical presentation in this patient and reviews the literature on the currently published cases.
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- 2022
5. The Use of Single Therapy With Tocilizumab Versus Combination Therapy With Remdesivir and Tocilizumab in SARS-CoV-2 Patients in El Paso, Texas
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Felix Emeka Anyiam, Suresh J. Antony, Roberto Guevara, Syed Haq, Nouf K Almaghlouth, Mohamed J Attia, and Sidra Shah
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medicine.medical_specialty ,Combination therapy ,Pulmonology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Infectious Disease ,remdesivir ,Logistic regression ,law.invention ,chemistry.chemical_compound ,tocilizumab ,Tocilizumab ,Randomized controlled trial ,law ,Internal medicine ,Internal Medicine ,Medicine ,business.industry ,ventilation ,General Engineering ,mortality ,clinical outcomes ,chemistry ,Methylprednisolone ,covid-19 ,Mann–Whitney U test ,Observational study ,sars cov-2 ,business ,medicine.drug - Abstract
Background Currently, the management of SARS-CoV-2 varies with no definitive clinical guidelines, as scientific evidence across the globe differs in therapeutic options. This study intended to provide some clarity to the insufficient data based on the role of monotherapy with tocilizumab (TCZ) and combination therapy with remdesivir (RDV) and TCZ among patients with SARS-CoV-2 infection in El Paso, Texas. We evaluated the use of each therapy in the presence of steroids as the standard of care. Methods One hundred and fifty-four SARS-CoV-2-infected patients from four different medical centers in El Paso, Texas, were screened, with 113 eligible for this longitudinal comparative observational study (February 1, 2020 to October 31, 2020). Group 1 (80 patients) received TCZ in the first 24 hours following admission, then methylprednisolone for the next 72 hours and group 2 (33 patients) were given TCZ as detailed in the single therapy group, plus RDV within the first 24 hours. Mann Whitney U test assessed median differences in laboratory biomarkers and Bivariate Logistic Regression assessed the odds of risk. An observation is considered statistically significant when P-value is ≤0.05. Results Patients in group 1 had a statistically significant lower odds for ventilation use than group 2 (OR=0.34, 95%CI=0.12-0.95, p=0.034), although no statistically significant difference in mortality outcomes was observed across groups (OR=0.43, 95%CI:0.13-1.39, p=0.269). Conclusions We concluded that the use of TCZ in SARS-CoV-2-infected patients in El Paso, with or without RDV, reported no mortality benefit. However, some minimal/non-use of ventilation benefit was observed in group 1. Nonetheless, a randomized controlled trial study is recommended to ultimately determine the combination role of TCZ and RDV among this highly vulnerable group of patients.
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- 2021
6. D-Pinitol improves cognitive dysfunction and neuronal damage induced by isoproterenol via modulation of NF-κB/BDNF/GFAP signaling in Swiss albino mice
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Aamir Khan, Sumit Sharma, Anwesha Das, Mumtaz Alam, Mansoor Ali Syed, and Syed Haque
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d-pinitol ,inflammation ,isoproterenol ,neuroprotection ,neurotoxicity ,oxidative stress ,Medicine - Abstract
Objective(s): Neurological disorders are the world’s most distressing problem. The adverse effects of current medications continue to compel scientists to seek safer, more effective, and economically affordable alternatives. In this vein, we explored the effect of D-Pinitol on isoproterenol-induced neurotoxicity in mice.Materials and Methods: Forty-two mice were randomly distributed into 7 groups each having 6 animals. Group I; received saline. Group II; received isoproterenol (ISO) 15 mg/kg/day, s.c. for 20 days. Group III, IV; received 50 and 100 mg/kg/day/oral of D-Pinitol, respectively along with ISO for 20 days. Group V; received D-Pinitol 100 mg/kg/day/oral for 20 days. Group VI; received propranolol 20 mg/kg/day/oral and ISO for 20 days. Group VII; received propranolol 20 mg/kg/day/oral for 20 days. On the 21st day after behavioral tests, blood was collected and mice were sacrificed for various biochemical, histopathological, and immunohistochemical analyses.Results: Chronic administration of isoproterenol caused neurotoxicity, cognitive dysfunction, and histopathological changes in the brain as evidenced by increase in GFAP, oxidative stress (via SOD, CAT, TBARS, and GSH), neuroinflammation (NF-kB, TNF-α, IL-6, and IL-10), and decrease in AchE and BDNF. Co-administration of D-Pinitol (100 mg/kg) significantly prevented these pathological alterations. The cognitive improvement was also observed through the forced swim test, elevated plus maze test, and rotarod test.Conclusion: Our findings on D-Pinitol thus clearly established its neuroprotective role in ISO-induced neurodegeneration in Swiss albino mice.
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- 2024
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7. Enduring Benefits of Widespread TMS Implementation: Analysis of Data in Pennine Care NHS Foundation
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Donia El-Nemr, Stephanie Murch, Micheal Kurkar, Andi Stanescu, and Syed Haque
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Psychiatry ,RC435-571 - Abstract
Aims Transcranial Magnetic Stimulation (TMS), characterized by its non-invasiveness and absence of recovery time, emerges as an optimal intervention for treatment-resistant depression. Operating through the induction of a time-varying electric field in the brain, TMS elicits action potentials in cortical neurons, leading to long-term neural inhibition and excitation, fostering neuroplasticity. Despite its efficacy, TMS remains available in a limited number of National Health Service (NHS) hospitals. This study aims to evaluate the use of TMS for treatment resistant depression and its impact upon service utilisation within Pennine Care NHS Foundation Trust. Methods A retrospective analysis was conducted on 76 patients diagnosed with treatment-resistant depression. Responders (n = 54) and non-responders (n = 22) were identified based on baseline, midpoint and endpoint assessments using HDRS, Beck's Inventory, PHQ-9, and GAD anxiety questionnaires. Patient data was extracted from PARIS, the Electronic Patient Record system of Pennine Care NHS Foundation, encompassing NHS service utilisation pre- and post-TMS treatment. Results Comparison between 12 months pre and post-TMS treatment revealed noteworthy findings: 12 responders (22%) were admitted to hospital in the year prior to starting treatment with a total of 1134 and mean of 94.5 days. In comparison to post-TMS where 11 (20.4%) patients had total of 913 and mean of 83 days. 8 non-responders (36.4%) were admitted to hospital in the year prior to starting treatment with a total of 285 and mean of 36.5 days. In comparison to post-TMS where 3 (13.6%) patients had a total of 276 and mean of 92 days. Outpatient appointments reduced by 15.4% for responders and 27.2% for non-responders. Number of A&E admissions reduced by 79.3% for responders and 65.5% for non-responders. Admissions to Home Treatment Team (HTT) decreased by 62.7% for responders and 86.7% for non-responders. Post-TMS discharge from services was 25.9% for responders and 18.2% for non-responders. Conclusion This study underscores a reduction in service utilisation among treatment-resistant depression patients following TMS treatment, with some indication that a greater reduction is seen for responders to treatment. While there was limited benefit seen when analysing outpatient appointments and HTT involvement, a greater reduction was seen when evaluating A&E attendance and days spent in hospital. In addition to exploring the possibility of late response to treatment and how this affects non-responder data, future studies are needed to compare results with patients who did not have TMS. These studies will require larger study numbers to better analyse the enduring benefits of widespread TMS implementation within the NHS.
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- 2024
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8. The impact of COVID-19 on the aesthetics industry
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Syed Haq and Alexandra Mills Haq
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Coronavirus disease 2019 (COVID-19) ,Aesthetics ,Political science - Published
- 2021
9. Implication of coughing dynamics on safe social distancing in an indoor environment—A numerical perspective
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Syed Haq, Saad Akhtar, Tariq Shamim, Mahmoud A. Alzoubi, Jorge L. Alvarado, and J. P. Muthusamy
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Range (particle radiation) ,Environmental Engineering ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Geography, Planning and Development ,COVID-19 ,Face mask efficacy ,Building and Construction ,Mechanics ,Computational Fluid Dynamics ,Breakup ,Coughing evolution ,Article ,law.invention ,Age groups ,law ,Air conditioning ,Contamination range ,Ventilation (architecture) ,Particle ,business ,Disease transmission ,Civil and Structural Engineering ,Lagrangian modeling - Abstract
Coughing is a primary symptomatic pathway of respiratory or air-borne disease transmission, including COVID-19. Several parameters such as cougher's age, gender, and posture affect particle dispersion indoors. This study numerically investigates the transient cough evolution, contamination range, particle reach probability, and deposition fraction for different age groups of males and females in standing and sitting postures in a ventilated room. The efficacy of a cloth mask has also been studied with and without the influence of air ventilation. Validated Computational Fluid Dynamics methodology has been implemented to model complex physics such as turbulent buoyant cloud, particle-air interaction, particle collision/breakup, and droplet evaporation. Our results show that overall, the contamination range is slightly lower for females due to lower cough velocities and particle counts. Moreover, a significant fraction of particles crosses the two meters social distancing guideline threshold with an unhindered cough. Besides, wearing a cloth mask reduces the average contamination range by approximately two-third of the distance compared to coughing without the mask. However, aerosolized particles reach longer streamwise distances and drift for extended durations beyond thirty seconds. This study can be used to improve the heating, ventilation, and air conditioning recommendations and distancing guidelines in indoor settings.
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- 2021
10. Disseminated Coccidioidomycosis Refractory to Multi-Drug Therapies in an Immunocompetent Patient
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Razi Syed Haq
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medicine.medical_specialty ,biology ,Coccidioides immitis ,business.industry ,Disseminated coccidioidomycosis ,medicine.disease ,biology.organism_classification ,Sepsis ,Internal medicine ,Amphotericin B ,medicine ,Disseminated disease ,Coccidioides ,business ,Fluconazole ,Immunodeficiency ,medicine.drug - Abstract
Coccidioidomycosis is a fungal infection caused by Coccidioides immitis which thrives in dry desert climates such as the southwestern United States. Disseminated coccidioidomycosis is often seen in patients with an underlying immunodeficiency. Historically there have been few reported cases of opportunistic infections in the setting of low CD4+ count and no evidence of HIV infection. Coccidioidomycosis typically presents asymptomatically or as a minor respiratory illness in immunocompetent individuals. We report a case of disseminated coccidioidomycosis in a patient who is otherwise immunocompetent. Patient is a 24-year-old Hispanic male who presented with severe headache, fever, body pain, vomiting, and diarrhea for approximately 14 days. On admission, patient’s CD4+ count was 91 and CSF culture grew Coccidioides immitis, for which patient was started on fluconazole. Patient’s hospital stay was complicated by multiple bouts of altered mental status, fevers, hyponatremia, hydrocephalus, neurogenic bladder, new-onset Mobitz II heart arrhythmia, urinary tract infection, and sepsis. MRI studies revealed abnormal enhancement of leptomeninges, bilateral basal ganglia, thecal sac and cauda equina fibers, signifying disseminated disease. Patient’s serum Coccidioides complement fixation (IgG) titers remained elevated despite aggressive therapy with IV amphotericin B. After a total of six months of hospitalization, including treatment with intrathecal amphotericin B, patient’s last CD4+ count was 549, CSF IgG titers achieved
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- 2019
11. Wernicke’s Encephalopathy: An Overlooked Cause
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Lloyd Muzangwa, Carlos Rivera, Jay Nfonoyim, Jose Luis Valdes Bracamontes, Razi Syed Haq, Joseph Bibawy, Samuel J Beaujean, Charlota Jurcik, and Vaithilingam Arulthasan
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Pediatrics ,medicine.medical_specialty ,business.industry ,Medicine ,business ,medicine.disease ,Wernicke's encephalopathy - Published
- 2019
12. EFFECTIVENESS OF MICRO-DROPLET TRAIN AND MICRO-JET IMPINGEMENT IN SURFACE COOLING
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Jorge L. Alvarado, J. P. Muthusamy, Taolue Zhang, and Syed Haq
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Materials science ,Heat transfer enhancement ,Volume of fluid method ,Jet impingement ,Mechanics ,Surface cooling - Published
- 2019
13. 15491 Systematic literature review examining efficacy of abobotulinumtoxinA for esthetic indications
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Said Hilton, Syed Haq, Alessandra Nogueira, Inna Prygova, Joel L Cohen, Maurizio Viel, Marina Landau, Andreas Nikolis, Mark S Nestor, and Alessio Redaelli
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Psychotherapist ,Systematic review ,business.industry ,Medicine ,Dermatology ,business - Published
- 2020
14. Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats
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Sumit Sharma, Ashif Iqubal, Vasim Khan, Kalicharan Sharma, Abul Najmi, and Syed Haque
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epimedium ,heart failure ,nf-kappab ,oxidative stress ,sildenafil ,Medicine - Abstract
Objective(s): Cardiovascular diseases are widespread across the globe, and heart failure (HF) accounts for the majority of heart-associated deaths. Target-based drug therapy is much needed for the management of heart failure. We have designed this study to evaluate icariin for its cardioprotective activity in the isoproterenol (ISO) induced postinfarction model. We have randomly distributed Wistar rats into seven groups, i.e., vehicle control; isoproterenol-treated; icariin per se; sildenafil per se; ISO + icariin 5; ISO + icariin 10; and ISO + sildenafil groups. ISO (85 mg/kg, subcutaneous) was administered at 24 hr for two consecutive days to produce cardiac injury, followed by icariin administration at 5 mg/kg and 10 mg/kg orally for 56 days.Materials and Methods: Rats were subjected to hemodynamic measurements biweekly. After 24 hr of the completion of dosing, animals were sacrificed, and markers for oxidative stress, fibrosis, inflammation, and cell death were measured. Transmission electron microscopy (TEM), histopathology, and MT staining of cardiac tissue were also done to assess the pathological and fibrotic architectural damage. Results: A significant decline in hemodynamics and an antioxidant collapse were found in ISO-intoxicated rats. Alterations in the levels of cyclic guanosine monophosphate (cGMP), interleukin-10 (IL-10), Tumor necrosis factor (TNF-α), and brain natriuretic peptide (BNP) were also observed in serum. Up-regulation of caspase-3, nuclear factor (NF-ĸB), and decline in expression of nuclear factor (NrF-2) contribute to cardiac damage. The treatment with icariin and sildenafil considerably reversed the toxic changes toward normal.Conclusion: Increased cGMP and Nrf2 expression and suppressed NF-ĸB-caspase-3 signaling play a pivotal role in icariin-mediated cardioprotection.
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- 2023
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15. Systematic literature review examining the efficacy of abobotulinumtoxinA in aesthetic indications
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Alessio Redaelli, Maurizio Viel, Marina Landau, Syed Haq, Andreas Nikolis, Inna Prygova, Joel L Cohen, and Mark S Nestor
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Systematic review ,Psychotherapist ,Toxicology ,Psychology - Published
- 2018
16. Saroglitazar ameliorates monosodium glutamate-induced obesity and associated inflammation in Wistar rats: Plausible role of NLRP3 inflammasome and NF- κB
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Sayima Nabi, Uma Bhandari, and Syed Haque
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inflammation ,low-density lipoprotein - receptors ,monosodium glutamate ,nlrp3 inflammasome nuclear factor - kappa b ,obesity ,saroglitazar ,Medicine - Abstract
Objective(s): Inflammation is the major progenitor of obesity and associated metabolic disorders. The current study investigated the modulatory role of saroglitazar on adipocyte dysfunction and associated inflammation in monosodium glutamate (MSG) obese Wistar rats.Materials and Methods: The molecular docking simulation studies of saroglitazar and fenofibrate were performed on the ligand-binding domain of NLRP3 and NF- κB. Under in vivo study, neonatal pups received normal saline or MSG (4 g/kg, SC) for 7 alternate days after birth. After keeping for 42 days as such, animals were divided into seven groups: Normal control; MSG control; MSG + saroglitazar (2 mg/kg); MSG + saroglitazar (4 mg/kg); saroglitazar (4 mg/kg) per se; MSG + fenofibrate (100 mg/kg); fenofibrate (100 mg/kg) per se. Drug treatments were given orally, from the 42nd to 70th day. On day 71, blood was collected and animals were sacrificed for isolation of liver and fat pads. Results: In silico study showed significant binding of saroglitazar and fenofibrate against NLRP3 and NF- κB. Saroglitazar significantly reduced body weight, body mass index, Lee’s index, fat pad weights, adiposity index, decreased serum lipids, interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), leptin, insulin, blood glucose, HOMA-IR values, oxidative stress in the liver and increased hepatic low-density lipoprotein receptor levels. Histopathological analysis of the liver showed decreased inflammation and vacuolization, and reduced adipocyte cell size. Immunohistochemical analysis showed suppression of NLRP3 in epididymal adipocytes and NF- κB expression in the liver. Conclusion: Saroglitazar ameliorated obesity and associated inflammation via modulation of NLRP3 inflammasome and NF- κB in MSG obese Wistar rats.
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- 2022
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17. Novel Copolymers of Styrene. 3. Halogen Ring-Substituted Ethyl 2-Cyano-3-Phenyl-2-Propenoates
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Gregory B. Kharas, Eric S. Molina, Kathleen E. Abma, Roshan A. Ali, Kiki D. Bairaktaris, Fred P. Biasiello, Eva A. Cygan, Jami Gibson, Syed Haq, Dawn E. Hoag, Kasandra Johnson, Shenik I. Jordan, Michael B. Mathews, Caitlyn A. Shadduck, and Nora Tuzik
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Polymers and Plastics ,General Chemistry ,Styrene ,chemistry.chemical_compound ,Monomer ,chemistry ,Electrophile ,Polymer chemistry ,Materials Chemistry ,Ceramics and Composites ,Copolymer ,Reactivity (chemistry) ,Knoevenagel condensation ,Piperidine ,Polystyrene - Abstract
Electrophilic trisubstituted ethylenes, ring-substituted ethyl 2-cyano-3-phenyl-2-propenoates, RPhCH˭C(CN)CO2C2H5 (where R is 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-F, 3-F, 4-F, 2-Cl-4-F, 2-Cl-6-F, 3-Cl-4-F) were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and ethyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C-NMR. All the ethylenes were copolymerized with styrene (M1) in solution with radical initiation (ABCN) at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, 1H and 13C-NMR. The order of relative reactivity (1/r 1) for the monomers is 4-Br (7.74) > 2-Br (1.62) > 3-Cl (1.56) > 3-Br (1.39) > 4-F (0.97) > 3-F (0.86) = 4-Cl (0.86) > 2-Cl-6-F (0.57) > 3-Cl-4-F (0.51) > 2-Cl (0.49) > 2-F (0.42) > 2-Cl-4-F (0.37). Relatively high Tg of the copolymers in comparison with that of polystyrene indicates a decrease i...
- Published
- 2013
18. Effectiveness of ultrasound-guided local steroid injection to the wrist for the treatment of carpal tunnel syndrome: Is it worth it?
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Poornanand Goru, George C. Butaliu, Gopalkrishna G. Verma, Syed Haque, Abubakar Mustafa, and Ashok Paul
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Carpal tunnel syndrome ,Ultrasound guidance ,Steroid injection ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Carpal tunnel syndrome (CTS) is caused by compression of the median nerve at the wrist level and the most frequent entrapment neuropathy in the upper limb. It can be treated with surgical or non-surgical methods. When nonsurgical treatment is indicated, a local corticosteroid injection into the carpal tunnel can be used to reduce pain and tingling sensation. To assess the clinical outcomes and effectiveness of patient satisfaction following ultrasound-guided steroid injection for the treatment of carpal tunnel syndrome. Results The study comprises 44 female (73%) and 16 (27%) male patients, with a mean age of 57 (27–84) years. Thirty-one patients were left-handed and 29 right-handed. Twenty-six (43%) injections were performed on the right side, 8 (13%) on the left, and 26 were bilateral. Fifty-six hands of thirty-seven (70%) patients reported significant improvement symptoms, five (8%) had temporary improvement with recurrence, seventeen patients (28%) failed to improve, and one patient’s symptoms have resolved before intervention. Among temporary responders and nonresponders, two were referred to the neurologist for further evaluation. Out of twenty patients, fourteen patients (23%) had surgical decompression of carpal tunnel with complete resolution of symptoms, four patients had opted for repeat injections, and two patients refused any further intervention. Conclusions The use of ultrasound-guided injection for the treatment of mild to moderate carpal tunnel syndrome is a practical procedure before offering surgical treatment. It is also appropriate for the patient with significant medical problems or not willing to undergo surgical intervention. Its ultrasound guide reduces injection-related complications, improves patient satisfaction, is cost-effective, and improves patient compliance.
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- 2022
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19. Multinational, Multipatient Study of Calcium Hydroxylapatite for Treatment of the Aging Hand
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Ragnar Storck, Anwar Thio, Constance Campion, Joan Fontdevilla, Eric Essayagh, Syed Haq, Martine Baspeyras, and Ravi Jain
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medicine.medical_specialty ,business.industry ,Treatment options ,Postmarketing surveillance ,Dermatology ,General Medicine ,Satisfaction rating ,Surgery ,Medical product ,Physical therapy ,Medicine ,Patient treatment ,business ,Adverse effect ,Calcium hydroxylapatite ,After treatment - Abstract
RESULTS Final results showed that 86% of patients were satisfied or better on a 6-point scale. At week 12, investigators expressed high satisfaction, with a 93% satisfaction rating or better. At weeks 2 and 12, physicians evaluated 98% of patients as improved or better on the Global Aesthetic Improvement Scale. Mild adverse events generally resolved within 2 weeks. Three cases of delayed edema reported 7 to 14 days after treatment resolved without intervention. CONCLUSION Ease of use, minimal postprocedure events, desirable cosmetic outcome, and duration underscore the benefits of CaHA as a safe, efficient, noninvasive treatment option for the aging hand. BioForm Medical Europe commissioned this study and the attendant postmarketing surveillance. BioForm Medical Europe reimbursed each physician a designated sum for each completed patient treatment, including five sets of questionnaires and photos. In return for their participation and completion of the Media Release Form, patients received a maximum of three syringes of BioForm Medical product for treatment of the hands. The individual treating physician determined total cost of treatment.
- Published
- 2010
20. Glucose phosphorylation is required for insulin-dependent mTOR signalling in the heart
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Heinrich Taegtmeyer, Patrick H. Guthrie, Suzanne S. Chan, Saumya Sharma, and Syed Haq
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Male ,medicine.medical_specialty ,Physiology ,Glucose uptake ,Blotting, Western ,Cell Cycle Proteins ,Biology ,mTORC2 ,Article ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Insulin ,Myocytes, Cardiac ,Phosphorylation ,Protein kinase B ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,Adaptor Proteins, Signal Transducing ,Pentosephosphates ,Hexokinase ,Kinase ,TOR Serine-Threonine Kinases ,RPTOR ,Ribosomal Protein S6 Kinases, 70-kDa ,Hexosamines ,Phosphoproteins ,Rats ,Glucose ,Endocrinology ,Animals, Newborn ,chemistry ,Cardiology and Cardiovascular Medicine ,Glycolysis ,Protein Kinases ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Objective Insulin regulates both glucose uptake and postnatal cardiac growth. The anabolic effects of insulin are mediated by the mammalian target of rapamycin (mTOR), an evolutionarily conserved kinase which is also a convergence point between nutrient sensing and cell growth. We postulated that mTOR signalling in the heart requires the metabolism of glucose. Methods We interrogated the insulin-mediated mTOR signalling pathway in response to different metabolic interventions regulating substrate metabolism in the isolated working rat heart and in isolated cardiomyocytes. Results Although insulin enhanced Akt activity, phosphorylation of mTOR and its downstream targets (p70S6K and 4EBP1) required the addition of glucose. Glucose-dependent p70S6K phosphorylation was independent of the hexosamine biosynthetic pathway, the AMP kinase pathway, and the pentose phosphate pathway. However, inhibition of glycolysis downstream of hexokinase markedly enhanced p70S6K phosphorylation. Furthermore, 2-deoxyglucose activated p70S6K suggesting that phosphorylation of glucose is required for carbohydrate-mediated mTOR signalling in the heart. Lastly, we also found enhanced p70S6K phosphorylation in the hearts of diabetic rats. Conclusion Phosphorylation of glucose is necessary for insulin-dependent mTOR activity in the heart, suggesting a link between intermediary metabolism and cardiac growth.
- Published
- 2007
21. Glycogen Synthase Kinase-3β Regulates Growth, Calcium Homeostasis, and Diastolic Function in the Heart
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Ashour Michael, Robert N. Solomon, Jeffery D. Molkentin, Richard D. Patten, Syed Haq, Ronglih Liao, Zhili Shao, Lei Cui, Muthu Periasamy, Thomas Force, Michele Andreucci, Eileen Hsich, Xin Chen, Kausik Bhattacharya, Heiko Kilter, Gordon S. Huggins, and Brian Walters
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Cardiac function curve ,medicine.medical_specialty ,Atrial enlargement ,Systole ,Diastole ,Mice, Transgenic ,Calcium-Transporting ATPases ,In Vitro Techniques ,Biology ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Sarcoplasmic Reticulum Calcium-Transporting ATPases ,Glycogen Synthase Kinase 3 ,Mice ,GSK-3 ,Internal medicine ,medicine ,Animals ,Homeostasis ,Promoter Regions, Genetic ,Molecular Biology ,GSK3B ,Calcium metabolism ,Muscle Cells ,Glycogen Synthase Kinase 3 beta ,Heart ,Cell Biology ,medicine.disease ,Recombinant Proteins ,Cardiovascular physiology ,Endocrinology ,Heart failure ,Calcium ,Female ,medicine.symptom - Abstract
Glycogen synthase kinase (GSK) 3beta is a negative regulator of stress-induced cardiomyocyte hypertrophy. It is not clear, however, if GSK-3beta plays any role in regulating normal cardiac growth and cardiac function. Herein we report that a transgenic mouse expressing wild type GSK-3beta in the heart has a dramatic impairment of normal post-natal cardiomyocyte growth as well as markedly abnormal cardiac contractile function. The most striking phenotype, however, is grossly impaired diastolic relaxation, which leads to increased filling pressures of the left ventricle and massive atrial enlargement. This is due to profoundly abnormal calcium handling, leading to an inability to normalize cytosolic [Ca2+] in diastole. The alterations in calcium handling are due at least in part to direct down-regulation of the sarcoplasmic reticulum calcium ATPase (SERCA2a) by GSK-3beta, acting at the level of the SERCA2 promoter. These studies identify GSK-3beta as a regulator of normal growth of the heart and are the first of which we are aware, to demonstrate regulation of expression of SERCA2a, a critical determinant of diastolic function, by a cytosolic signaling pathway, the activity of which is dynamically modulated. De-regulation of GSK-3beta leads to severe systolic and diastolic dysfunction and progressive heart failure. Because down-regulation of SERCA2a plays a central role in the diastolic and systolic dysfunction of patients with heart failure, these findings have potential implications for the therapy of this disorder.
- Published
- 2004
22. Stabilization of β-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth
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Kausik Bhattacharya, James R. Woodgett, Brian F. Walters, Ashour Michael, Heiko Kilter, Syed Haq, Paolo Dotto, Michele Andreucci, and Thomas Force
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Beta-catenin ,Cellular differentiation ,Receptors, Cell Surface ,Protein Serine-Threonine Kinases ,Glycogen Synthase Kinase 3 ,Phenylephrine ,Drug Stability ,GSK-3 ,Proto-Oncogene Proteins ,Heterotrimeric G protein ,Animals ,Myocytes, Cardiac ,Glycogen synthase ,Cells, Cultured ,beta Catenin ,Multidisciplinary ,Endothelin-1 ,biology ,Gene Transfer Techniques ,Wnt signaling pathway ,Hypertrophy ,Zebrafish Proteins ,Biological Sciences ,Heterotrimeric GTP-Binding Proteins ,Rats ,Cell biology ,Wnt Proteins ,Cytoskeletal Proteins ,Catenin ,Trans-Activators ,biology.protein ,Signal transduction ,Proto-Oncogene Proteins c-akt ,Cell Division ,Signal Transduction - Abstract
β-Catenin is a transcriptional activator that regulates embryonic development as part of the Wnt pathway and also plays a role in tumorigenesis. The mechanisms leading to Wnt-induced stabilization of β-catenin, which results in its translocation to the nucleus and activation of transcription, have been an area of intense interest. However, it is not clear whether stimuli other than Wnts can lead to important stabilization of β-catenin and, if so, what factors mediate that stabilization and what biologic processes might be regulated. Herein we report that β-catenin is stabilized in cardiomyocytes after these cells have been exposed to hypertrophic stimuli in culture or in vivo . The mechanism by which β-catenin is stabilized is distinctly different from that used by Wnt signaling. Although, as with Wnt signaling, inhibition of glycogen synthase kinase-3 remains central to hypertrophic stimulus-induced stabilization of β-catenin, the mechanism by which this occurs involves the recruitment of activated PKB to the β-catenin-degradation complex. PKB stabilizes the complex and phosphorylates glycogen synthase kinase-3 within the complex, inhibiting its activity directed at β-catenin. Finally, we demonstrate via adenoviral gene transfer that β-catenin is both sufficient to induce growth in cardiomyocytes in culture and in vivo and necessary for hypertrophic stimulus-induced growth. Thus, in these terminally differentiated cells, β-catenin is stabilized by hypertrophic stimuli acting via heterotrimeric G protein-coupled receptors. The stabilization occurs via a unique Wnt-independent mechanism and results in cellular growth.
- Published
- 2003
23. Stretch-activated pathways and left ventricular remodeling
- Author
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Thomas Force, Heiko Kilter, Syed Haq, and Ashour Michael
- Subjects
Integrins ,medicine.medical_specialty ,Cell signaling ,Volume overload ,Stimulus (physiology) ,Pathogenesis ,GTP-Binding Proteins ,Internal medicine ,medicine ,Animals ,Humans ,Myocytes, Cardiac ,Myocardial infarction ,Insulin-Like Growth Factor I ,Ventricular remodeling ,Heart Failure ,Endothelin-1 ,Ventricular Remodeling ,Interleukin-6 ,business.industry ,Angiotensin II ,medicine.disease ,Myocardial Contraction ,Cellular signal transduction ,Heart failure ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Neuroscience ,Signal Transduction - Abstract
Stretch of cardiomyocytes in vivo occurs in response to a number of stimuli, including pressure or volume overload, but it is most clearly seen following relatively large, acute myocardial infarctions. It is in this setting that stretch is most clearly related to the pathogenesis of heart failure. Stretch of the remote, noninfacted myocardium leads to the activation of a large number of cellular signal transduction pathways, which sets into motion a series of what are designed to be compensatory responses to the increased wall stress on the surviving myocardium. Herein, we will discuss the cellular pathways activated by cell stretch, which appear to trigger the initial steps in the pathogenesis of ventricular dilatation following myocardial infarction. We will discuss what is known of the "stretch sensors," which convert the mechanical stimulus into molecular signals. I will then introduce the specific cellular signaling pathways activated by stretch and discuss the evidence for their involvement in remodeling. Since many of these pathways will be covered in more detail in specific sections to follow, this will serve as an introduction to stretch-activated signaling. Finally, we will briefly examine later phases of the response, including advanced heart failure. The goal is to identify molecular modulators that might serve as targets for pharmacologic or molecular intervention.
- Published
- 2002
24. Calcineurin Promotes Protein Kinase C and c-Jun NH2-terminal Kinase Activation in the Heart
- Author
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Leon J. De Windt, Jeffery D. Molkentin, Syed Haq, Thomas Force, and Hae W. Lim
- Subjects
MAPK/ERK pathway ,biology ,Kinase ,Chemistry ,p38 mitogen-activated protein kinases ,Cell Biology ,Biochemistry ,Cell biology ,Calcineurin ,Enzyme activator ,Mitogen-activated protein kinase ,biology.protein ,Cancer research ,Signal transduction ,Molecular Biology ,Protein kinase C - Abstract
Multiple intracellular signaling pathways have been shown to regulate the hypertrophic growth of cardiomyocytes. Both necessary and sufficient roles have been described for the mitogen activated protein kinase(1) (MAPK) signaling pathway, specific protein kinase C (PKC) isoforms, and calcineurin. Here we investigate the interdependence between calcineurin, MAPK, and PKC isoforms in regulating cardiomyocyte hypertrophy using three separate approaches. Hearts from hypertrophic calcineurin transgenic mice were characterized for PKC and MAPK activation. Transgenic hearts demonstrated activation of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2), but not p38 MAPK factors. Calcineurin transgenic hearts demonstrated increased activation of PKCalpha, beta(1), and theta, but not of epsilon, beta(2), or lambda. In a second approach, cultured cardiomyocytes were infected with a calcineurin adenovirus to induce hypertrophy and the effects of pharmacologic inhibitors or co-infection with a dominant negative adenovirus were examined. Calcineurin-mediated hypertrophy was prevented with PKC inhibitors, Ca(2+) chelation, and attenuated with a dominant negative SEK-1 (MKK4) adenovirus, but inhibitors of ERK or p38 activation had no effect. In a third approach, we examined the activation of MAPK factors and PKC isoforms during the progression of load-induced hypertrophy in aortic banded rats with or without cyclosporine. We determined that inhibition of calcineurin activity with cyclosporine prevented PKCalpha, theta, and JNK activation, but did not affect PKCepsilon, beta, lambda, ERK1/2, or p38 activation. Collectively, these data indicate that calcineurin hypertrophic signaling is interconnected with PKCalpha, theta, and JNK in the heart, while PKCepsilon, beta, lambda, p38, and ERK1/2 are not involved in calcineurin-mediated hypertrophy.
- Published
- 2000
25. Myth 4. That Medieval Islamic Culture Was Inhospitable to Science
- Author
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Syed Haq
- Published
- 2009
26. The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy
- Author
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Sergei P. Shevtsov, Risto Kerkelä, Ronglih Liao, Richard D. Patten, Mark Aronovitz, Thomas Force, Robert N. Salomon, Eileen Hsich, Lei Cui, Syed Haq, Xin Chen, and Jeffery D. Molkentin
- Subjects
medicine.medical_specialty ,Beta-catenin ,animal structures ,Lymphoid Enhancer-Binding Factor 1 ,Cellular differentiation ,T cell ,Cardiomegaly ,Mice, Transgenic ,Cell Enlargement ,TCF/LEF family ,Mice ,Internal medicine ,Coactivator ,medicine ,Animals ,Myocytes, Cardiac ,Enhancer ,Molecular Biology ,Transcription factor ,beta Catenin ,Cell Proliferation ,Mice, Knockout ,biology ,Heart ,Cell Biology ,Articles ,Mice, Mutant Strains ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Endocrinology ,Phenotype ,embryonic structures ,Mutation ,biology.protein ,TCF Transcription Factors ,Gene Deletion ,Lymphoid enhancer-binding factor 1 ,Signal Transduction - Abstract
In cells capable of entering the cell cycle, including cancer cells, beta-catenin has been termed a master switch, driving proliferation over differentiation. However, its role as a transcriptional activator in terminally differentiated cells is relatively unknown. Herein we utilize conditional, cardiac-specific deletion of the beta-catenin gene and cardiac-specific expression of a dominant inhibitory mutant of Lef-1 (Lef-1Delta20), one of the members of the T-cell factor/lymphocyte enhancer factor (Tcf/Lef) family of transcription factors that functions as a coactivator with beta-catenin, to demonstrate that beta-catenin/Tcf/Lef-dependent gene expression regulates both physiologic and pathological growth (hypertrophy) of the heart. Indeed, the profound nature of the growth impairment of the heart in the Lef-1Delta20 mouse, which leads to very early development of heart failure and premature death, suggests beta-catenin/Tcf/Lef targets are dominant regulators of cardiomyocyte growth. Thus, our studies, employing complementary models in vivo, implicate beta-catenin/Tcf/Lef signaling as an essential growth-regulatory pathway in terminally differentiated cells.
- Published
- 2006
27. 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling
- Author
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Christian Grohé, Michael E. Mendelsohn, Richard H. Karas, Ashour Michael, Mark Aronovitz, Xin Chen, Richard D. Patten, Thomas Force, Syed Haq, Flore Celestin, Isaac Pourati, Simone Nuedling, and Jason Baur
- Subjects
medicine.medical_specialty ,Physiology ,Morpholines ,Ovariectomy ,Recombinant Fusion Proteins ,Myocardial Infarction ,Caspase 3 ,Apoptosis ,Pharmacology ,Biology ,DNA laddering ,Protein Serine-Threonine Kinases ,Amino Acid Chloromethyl Ketones ,Wortmannin ,chemistry.chemical_compound ,Mice ,Phosphatidylinositol 3-Kinases ,Estrogen Receptor Modulators ,In vivo ,Internal medicine ,Proto-Oncogene Proteins ,medicine ,Animals ,Myocytes, Cardiac ,Phosphorylation ,Protein kinase B ,Fulvestrant ,Cells, Cultured ,Phosphoinositide-3 Kinase Inhibitors ,Mitogen-Activated Protein Kinase 1 ,TUNEL assay ,Mitogen-Activated Protein Kinase 3 ,Estradiol ,Rats ,Androstadienes ,Enzyme Activation ,Endocrinology ,chemistry ,Chromones ,Female ,Signal transduction ,Cardiology and Cardiovascular Medicine ,Protein Processing, Post-Translational ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Female gender and estrogen-replacement therapy in postmenopausal women are associated with improved heart failure survival, and physiological replacement of 17β-estradiol (E2) reduces infarct size and cardiomyocyte apoptosis in animal models of myocardial infarction (MI). Here, we characterize the molecular mechanisms of E2 effects on cardiomyocyte survival in vivo and in vitro. Ovariectomized female mice were treated with placebo or physiological E2 replacement, followed by coronary artery ligation (placebo-MI or E2-MI) or sham operation (sham) and hearts were harvested 6, 24, and 72 hours later. After MI, E2 replacement significantly increased activation of the prosurvival kinase, Akt, and decreased cardiomyocyte apoptosis assessed by terminal deoxynucleotidyltransferase dUTP nick-end labeling (TUNEL) staining and caspase 3 activation. In vitro, E2 at 1 or 10 nmol/L caused a rapid 2.7-fold increase in Akt phosphorylation and a decrease in apoptosis as measured by TUNEL staining, caspase 3 activation, and DNA laddering in cultured neonatal rat cardiomyocytes. The E2-mediated reduction in apoptosis was reversed by an estrogen receptor (ER) antagonist, ICI 182,780, and by phospho-inositide-3 kinase inhibitors, LY294002 and Wortmannin. Overexpression of a dominant negative-Akt construct also blocked E2-mediated reduction in cardiomyocyte apoptosis. These data show that E2 reduces cardiomyocyte apoptosis in vivo and in vitro by ER- and phospho-inositide-3 kinase–Akt–dependent pathways and support the relevance of these pathways in the observed estrogen-mediated reduction in myocardial injury.
- Published
- 2004
28. Deletion of cytosolic phospholipase A2 promotes striated muscle growth
- Author
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Ronglih Liao, Eileen O'Leary, Ashour Michael, J. Luis Guerrero, Brian Walters, Heiko Kilter, Joseph V. Bonventre, Michele Andreucci, Richard D. Patten, Xin Chen, Kausik Bhattacharya, Syed Haq, Xio Ming Sun, Michael H. Picard, Lei Cui, Thomas Force, Jeffery D. Molkentin, Anthony Rosenzweig, and Jingzang Tao
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Cardiomegaly ,Biology ,Protein Serine-Threonine Kinases ,General Biochemistry, Genetics and Molecular Biology ,Phospholipases A ,3-Phosphoinositide-Dependent Protein Kinases ,chemistry.chemical_compound ,Mice ,Phospholipase A2 ,Cytosol ,Internal medicine ,medicine ,Animals ,Insulin-Like Growth Factor I ,Protein kinase A ,Muscle, Skeletal ,Protein kinase C ,Cells, Cultured ,Protein Kinase C ,Arachidonic Acid ,Growth factor ,Skeletal muscle ,General Medicine ,Organ Size ,Phosphoproteins ,Mice, Mutant Strains ,Cell biology ,Lymphocyte cytosolic protein 2 ,Phospholipases A2 ,medicine.anatomical_structure ,Endocrinology ,chemistry ,biology.protein ,Insulin Receptor Substrate Proteins ,lipids (amino acids, peptides, and proteins) ,Arachidonic acid ,Female ,Signal transduction ,Signal Transduction - Abstract
Generation of arachidonic acid by the ubiquitously expressed cytosolic phospholipase A2 (PLA2) has a fundamental role in the regulation of cellular homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA2 is a negative regulator of growth, specifically of striated muscle. We find that normal growth of skeletal muscle, as well as normal and pathologic stress-induced hypertrophic growth of the heart, are exaggerated in Pla2g4a-/- mice, which lack the gene encoding cytosolic PLA2. The mechanism underlying this phenotype is that cytosolic PLA2 negatively regulates insulin-like growth factor (IGF)-1 signaling. Absence of cytosolic PLA2 leads to sustained activation of the IGF-1 pathway, which results from the failure of 3-phosphoinositide-dependent protein kinase (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-zeta, a negative regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-zeta, correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic PLA2 and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways.
- Published
- 2003
29. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1
- Author
-
Joseph V. Bonventre, Cornelis Kramers, Tilman Matthaeus, Alessandro Alessandrini, Ang Chen, Syed Haq, Michele Andreucci, Ashour Michael, Thomas Force, and Kwon Moo Park
- Subjects
inorganic chemicals ,medicine.medical_specialty ,kidney ,Phalloidine ,Swine ,Vascular medicine and diabetes [UMCN 2.2] ,Biology ,Protein Serine-Threonine Kinases ,environment and public health ,Renal Circulation ,Wortmannin ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Adenosine Triphosphate ,Internal medicine ,Proto-Oncogene Proteins ,growth factors ,medicine ,Animals ,cell signaling ,Protein phosphorylation ,Phosphorylation ,Protein kinase A ,Protein kinase B ,hormones ,Kinase ,Akt/PKB signaling pathway ,hypoxia ,forkhead proteins ,Immunohistochemistry ,Rats ,Renal disorders [UMCN 5.4] ,Endocrinology ,chemistry ,Nephrology ,Reperfusion Injury ,LLC-PK1 Cells ,Mitogen-Activated Protein Kinases ,Adenosine triphosphate ,Proto-Oncogene Proteins c-akt - Abstract
Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK 1 cells result in phosphorylation of FKHR and FKHRL1. Background Cell death and survival pathways are critical determinants of epithelial cell fate after ischemia. Forkhead proteins have been implicated in the regulation of cellular survival. Methods and Results We have found that none of the forkhead family of proteins, FKHR, is phosphorylated after ischemia/reperfusion in the rat kidney. The time course of phosphorylation is similar to the time course of activation of the forkhead protein kinase Akt/protein kinase B (PKB), with maximal phosphorylation at 24 to 48 hours postreperfusion when the process of regeneration peaks. Extracellular signal-regulated kinase (ERK)1/2 activation has also been implicated as prosurvival in the injured kidney. ERK1/2 were phosphorylated in postischemic kidneys at 5, 30, and 90 minutes of reperfusion, with phosphorylation decreased by 24 and 48 hours. Immunocytochemical analysis revealed increased phospho-ERK1/2 in the thick ascending limb and isolated cells of the S3 segment, which have lost apical actin staining. To understand the relationship between forkhead phosphorylation, Akt, and ERK1/2, an in vitro model of injury was employed. After 40 minutes of chemical anoxia followed by dextrose addition for 20 minutes to replete adenosine triphosphate (ATP) levels, FKHR and FKHRL1 are phosphorylated. The levels of phospho-Akt are increased for at least 120 minutes after dextrose addition with a maximum at 20 minutes. Phosphorylation of Akt, FKHR, and FKHRL1 are phosphatidylinositol 3-kinase (PI 3-kinase) dependent since phosphorylation is reduced by the PI 3-kinase inhibitors, wortmannin, or LY294002. Inhibition of mitogen-activated protein kinase (MAPK)/ERK kinase (MEK1/2), the upstream activator of ERK1/2, has no effect on forkhead protein phosphorylation after chemical anoxia/dextrose addition. Conclusion We conclude that PI 3-kinase and Akt are activated after renal ischemia/reperfusion and that Akt phosphorylation leads to phosphorylation of FKHR and FKHRL1, which may affect epithelial cell fate in acute renal failure.
- Published
- 2003
30. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure
- Author
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Kevin M. Tymitz, Judith K. Gwathmey, Thomas Force, Gabriel Choukroun, Hae Lim, Roger J. Hajjar, Luanda Grazette, Ashour Michael, Syed Haq, Jeffery D. Molkentin, and Federica del Monte
- Subjects
Male ,medicine.medical_specialty ,Cardiomyopathy ,Cardiomegaly ,Protein Serine-Threonine Kinases ,p38 Mitogen-Activated Protein Kinases ,Muscle hypertrophy ,Glycogen Synthase Kinase 3 ,GSK-3 ,Physiology (medical) ,Internal medicine ,Proto-Oncogene Proteins ,medicine ,Humans ,Mitogen-Activated Protein Kinase 9 ,Protein kinase A ,Protein kinase B ,business.industry ,Calcineurin ,Glycogen Synthase Kinases ,Middle Aged ,medicine.disease ,Endocrinology ,Heart failure ,Calcium-Calmodulin-Dependent Protein Kinases ,Female ,Signal transduction ,Mitogen-Activated Protein Kinases ,Cardiology and Cardiovascular Medicine ,business ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Background —Left ventricular failure is commonly preceded by a period of hypertrophy. Intriguingly, many of the signaling pathways that have been implicated in the regulation of hypertrophy, including the 3 mitogen-activated protein kinases (MAPKs: extracellular signal-regulated kinase, stress-activated protein kinase, and p38), protein phosphatase, calcineurin, and the protein kinase Akt and its target glycogen synthase kinase-3 (GSK-3), also regulate the apoptotic response. Methods and Results —To understand the mechanisms that might regulate the progression of heart failure, we analyzed the activity of these signaling pathways in the hearts of patients with advanced heart failure, patients with compensated cardiac hypertrophy, and normal subjects. In patients with hypertrophy, neither the MAPK nor the Akt/GSK-3 pathways were activated, and the dominant signaling pathway was calcineurin. In failing hearts, calcineurin activity was increased but less so than in the hypertrophied hearts, and all 3 MAPKs and Akt were activated (and, accordingly, GSK-3β was inhibited), irrespective of whether the underlying diagnosis was ischemic or idiopathic cardiomyopathy. Conclusions —In the failing heart, there is a clear prohypertrophic activity profile, likely occurring in response to increased systolic wall stress and neurohormonal mediators. However, with the activation of these hypertrophic pathways, potent proapoptotic and antiapoptotic signals may also be generated. Therapies directed at altering the balance of activity of these signaling pathways could potentially alter the progression of heart failure.
- Published
- 2001
31. Glycogen synthase kinase-3beta is a negative regulator of cardiomyocyte hypertrophy
- Author
-
James R. Woodgett, Jeffrey D. Molkentin, Ashour Michael, Zhao Bin Kang, Alessandro Alessandrini, Takashi Matsui, Hardeep Ranu, Gabriel Choukroun, Syed Haq, Anthony Rosenzweig, Thomas Force, and Roger J. Hajjar
- Subjects
medicine.medical_specialty ,Cardiomegaly ,macromolecular substances ,heart ,030204 cardiovascular system & hematology ,Muscle hypertrophy ,03 medical and health sciences ,Glycogen Synthase Kinase 3 ,Phenylephrine ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,GSK-3 ,Internal medicine ,medicine ,Animals ,Nuclear protein ,Protein kinase A ,Glycogen synthase ,Transcription factor ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,biology ,Endothelin-1 ,NFATC Transcription Factors ,Kinase ,Myocardium ,Glycogen Synthase Kinases ,Nuclear Proteins ,Cell Biology ,adenovirus ,Cell biology ,Rats ,DNA-Binding Proteins ,Endocrinology ,Animals, Newborn ,Calcium-Calmodulin-Dependent Protein Kinases ,Mutation ,biology.protein ,nuclear factor of activated T cells ,protein kinase B ,Original Article ,Signal transduction ,Signal Transduction ,Transcription Factors - Abstract
Hypertrophy is a basic cellular response to a variety of stressors and growth factors, and has been best characterized in myocytes. Pathologic hypertrophy of cardiac myocytes leads to heart failure, a major cause of death and disability in the developed world. Several cytosolic signaling pathways have been identified that transduce prohypertrophic signals, but to date, little work has focused on signaling pathways that might negatively regulate hypertrophy. Herein, we report that glycogen synthase kinase-3beta (GSK-3beta), a protein kinase previously implicated in processes as diverse as development and tumorigenesis, is inactivated by hypertrophic stimuli via a phosphoinositide 3-kinase-dependent protein kinase that phosphorylates GSK-3beta on ser 9. Using adenovirus-mediated gene transfer of GSK-3beta containing a ser 9 to alanine mutation, which prevents inactivation by hypertrophic stimuli, we demonstrate that inactivation of GSK-3beta is required for cardiomyocytes to undergo hypertrophy. Furthermore, our data suggest that GSK-3beta regulates the hypertrophic response, at least in part, by modulating the nuclear/cytoplasmic partitioning of a member of the nuclear factor of activated T cells family of transcription factors. The identification of GSK-3beta as a transducer of antihypertrophic signals suggests that novel therapeutic strategies to treat hypertrophic diseases of the heart could be designed that target components of the GSK-3 pathway.
- Published
- 2000
32. Errata Names, Natures and Things
- Author
-
Syed Haq
- Published
- 1994
33. Translation, Commentary and Textual Notes
- Author
-
Syed Haq
- Subjects
Literature ,business.industry ,Philosophy ,media_common.quotation_subject ,Fourth degree ,Praise ,business ,media_common - Abstract
Praise be to God for perpetually bestowing upon us His gifts and favors, and for His benevolence. After this follow our prayers for our lord Muhammad and his family. Peace be upon them!
- Published
- 1994
34. Names, Natures and Things: A Prefatory Note on the Central Theme of the Kitāb Al-Ahjār
- Author
-
Syed Haq
- Subjects
Balance (metaphysics) ,Language change ,Philosophy ,media_common.quotation_subject ,Realm ,Doctrine ,Metaphysics ,Universal law ,Soul ,media_common ,Theme (narrative) ,Epistemology - Abstract
Jābir’s Science of Balance was at once a metaphysical doctrine and a methodological thesis. Viewed as metaphysical doctrine, it embodied a universal principle which governed not only the sublunar world of generation and corruption, but also that which lay beyond the Sphere (al-Falak) in the intangible (ghayr malmūsa) realm of the hypostases. Thus we read in the Ahjār that there is a characteristic Balance of the stars, their distances, and their. movements; and there is a Balance by means of which the Sphere manifests itself to man. But over and above these, there are Balances even of the Soul and the Intelligence,1 “beyond Which there is no end” (lā nihāya ba’d dhālik).2
- Published
- 1994
35. The Doctrinal Context of jābir’s Kitāb Al-Ahjār: Substance, Qualities and the Science of Balance
- Author
-
Syed Haq
- Subjects
Balance (metaphysics) ,Literature ,business.industry ,Philosophy ,media_common.quotation_subject ,Neoplatonism ,Context (language use) ,Orthodoxy ,Islam ,business ,media_common - Abstract
By the time Islam emerged on the world scene, the two towering giants of Greek philosophy, Plato and Aristotle, had been blended into Neoplatonism. In fact the marriage of the two sets of ideas had already been consummated when Porphyry (d. 309 A.D.) made it a philosophical orthodoxy that Plato and Aristotle were in agreement.1 Islam found itself heir to an Aristotle soaked in Neoplatonism both of the pagan Athenian as well as of the Christian Alexandrian kind, and inherited both the debates as well as the commentatorial preoccupations of the two schools.2
- Published
- 1994
36. A Critical Edition of Select text of the Kitāb Al-Ahjār
- Author
-
Syed Haq
- Subjects
Medieval philosophy ,Information retrieval ,Philosophy ,Critical edition ,Linguistics - Published
- 1994
37. Cardiac-specific expression of GSK-3 impairs cardiac growth and calcium handling, leading to systolic and diastolic dysfunction, heart failure, and premature death
- Author
-
Ashour Michael, Thomas Force, Jeffery D. Molkentin, Kausik Battacharya, Lei Cui, Ronglih Liao, Richard D. Patten, Syed Haq, Xin Chen, and Heiko Kilter
- Subjects
medicine.medical_specialty ,Premature death ,Dysfunction heart ,business.industry ,Calcium handling ,GSK-3 ,Internal medicine ,Cardiology ,Diastole ,Medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2003
38. Erratum: Deletion of cytosolic phospholipase A2 promotes striated muscle growth
- Author
-
Michele Andreucci, J. Luis Guerrero, Xio Ming Sun, Eileen O'Leary, Anthony Rosenzweig, Jingzang Tao, Richard D. Patten, Brian F. Walters, Syed Haq, Ashour Michael, Ronglih Liao, Michael H. Picard, Joseph V. Bonventre, Heiko Kilter, Thomas Force, Xin Chen, Lei Cui, Jeffery D. Molkentin, and Kausik Bhattacharya
- Subjects
Cytosol ,Phospholipase A ,Nat ,Chemistry ,Glomerular Mesangial Cell ,General Medicine ,Molecular biology ,General Biochemistry, Genetics and Molecular Biology ,Muscle hypertrophy - Abstract
Nat. Med. 9, 944–951 (2003) In the version of this article initially published online, the last sentence of the 'Isolation of Plag4a−/− and wild-type glomerular mesangial cells' section of the Methods contained an error. Both instances of 'μm' should read 'μM'. We regret the error.
- Published
- 2003
39. Glycogen Synthase Kinase-3beta Is a Negative Regulator of Cardiomyocyte Hypertrophy.
- Author
-
Syed Haq and Choukroun, Gabriel
- Subjects
- *
CARDIAC hypertrophy , *HEART cells , *PROTEIN kinases - Abstract
Examines the role of glycogen synthase kinase-3beta (GSK-3), a protein kinase in cardiomyocyte hypertrophy. Impact of cytosolic signaling pathways on hypertrophy regulation; Importance of the protein kinase inactivation in cardiomyocytic hypertrophy; Difference of GSK-3 from other protein kinases; Mechanism of the GSK-3 action.
- Published
- 2000
- Full Text
- View/download PDF
40. Profile of narcotic abuse in peninsula Malaysia
- Author
-
Syed Haq and Neil Buhrich
- Subjects
Adult ,Employment ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Medicine (miscellaneous) ,Heroin ,Peninsula ,medicine ,Humans ,General hospital ,geography ,geography.geographical_feature_category ,Kuala lumpur ,Traditional medicine ,business.industry ,Malaysia ,Opium ,medicine.disease ,Opioid-Related Disorders ,Substance abuse ,Psychiatry and Mental health ,Clinical Psychology ,Socioeconomic Factors ,Family medicine ,Income ,Narcotic abuse ,business ,medicine.drug - Abstract
Demographic and drug abuse characteristics of 3,484 new drug abuse contacts presenting to the General Hospital, Kuala Lumpur, Malaysia are reported. The large majority were heroin inhalers. They were different from the traditional Eastern opium inhalers and similar to Western heroin injectors in that they were young, male, single, and frequently unemployed. These features and the relative underrepresentation of Chinese suggest that the Chinese of this study did not learn narcotic abuse from opium-smoking relatives.
- Published
- 1980
41. Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH2-terminal kinases
- Author
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Michael H. Picard, Gabriel Choukroun, Syed Haq, Federica del Monte, Anthony Rosenzweig, Thomas Force, J. Luis Guerrero, Roger J. Hajjar, and Stefanie J. Fry
- Subjects
Male ,medicine.medical_specialty ,Gene Expression ,Blood Pressure ,Cardiomegaly ,Biology ,Article ,Adenoviridae ,Muscle hypertrophy ,Rats, Sprague-Dawley ,In vivo ,Internal medicine ,medicine ,Animals ,Mitogen-Activated Protein Kinase Kinases ,Pressure overload ,Activator (genetics) ,Kinase ,Myocardium ,c-jun ,Gene Transfer Techniques ,JNK Mitogen-Activated Protein Kinases ,General Medicine ,medicine.disease ,Rats ,Cell biology ,Enzyme Activation ,Endocrinology ,Heart failure ,Calcium-Calmodulin-Dependent Protein Kinases ,Mutation ,Mitogen-Activated Protein Kinases ,Signal transduction ,Protein Kinases ,Atrial Natriuretic Factor ,Signal Transduction - Abstract
Cardiac hypertrophy often presages the development of heart failure. Numerous cytosolic signaling pathways have been implicated in the hypertrophic response in cardiomyocytes in culture, but their roles in the hypertrophic response to physiologically relevant stimuli in vivo is unclear. We previously reported that adenovirus-mediated gene transfer of SEK-1(KR), a dominant inhibitory mutant of the immediate upstream activator of the stress-activated protein kinases (SAPKs), abrogates the hypertrophic response of neonatal rat cardiomyocytes to endothelin-1 in culture. We now report that gene transfer of SEK-1(KR) to the adult rat heart blocks SAPK activation by pressure overload, demonstrating that the activity of cytosolic signaling pathways can be inhibited by gene transfer of loss-of-function mutants in vivo. Furthermore, gene transfer of SEK-1(KR) inhibited pressure overload–induced cardiac hypertrophy, as determined by echocardiography and several postmortem measures including left ventricular (LV) wall thickness, the ratio of LV weight to body weight, cardiomyocyte diameter, and inhibition of atrial natriuretic factor expression. Our data suggest that the SAPKs are critical regulators of cardiac hypertrophy in vivo, and therefore may serve as novel drug targets in the treatment of hypertrophy and heart failure. J. Clin. Invest. 104:391–398 (1999).
42. Apoptosis signal-regulating kinase/nuclear factor-κB: A novel signaling pathway regulates cardiomyocyte hypertrophy
- Author
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Heiko Kilter, Ashour Michael, Thomas Force, and Syed Haq
- Subjects
Biochemistry ,G protein ,Kinase ,Physiology (medical) ,Heterotrimeric G protein ,Signal transduction ,Biology ,Cardiology and Cardiovascular Medicine ,Janus kinase ,Protein kinase B ,Transcription factor ,Protein kinase C ,Cell biology - Abstract
Since 1993, when Sadoshima et al1 published their observations on the role of Angiotensin II (Ang II) in the stretch-induced hypertrophic response of cardiomyocytes, we have known that peptide hormones were important in the development of hypertrophy stimulated by cell stretch, the initiating stimulus in pressure overload-induced hypertrophy and in the hypertrophy that occurs in the noninfarcted myocardium following a myocardial infarction. Ang II, as well as endothelin-1 (ET-1) and α-adrenergic agents, activate intracellular pathways by binding to 7 transmembrane-spanning receptors coupled to heterotrimeric G proteins of the Gq class. The critical role of this class of receptors and G proteins in pressure overload-induced hypertrophy was elegantly demonstrated by Ahkter et al2 who showed that cardiac specific expression in mice of a peptide that blocked signal transmission by Gq markedly blunted the hypertrophic response to aortic banding. See p 509 The question that has dominated the field of cardiomyocyte biology is how do these hormones, acting via their cognate receptors and Gq, trigger the hypertrophic response? One clear conclusion has evolved thus far: the hypertrophic response of cardiomyocytes is regulated by an enormously complex network of interacting cytosolic signaling pathways.3 Gq activation ultimately results in the production of intermediates that increase cytosolic free [Ca2+] and activate members of the protein kinase C family, and leads to the recruitment of several protein kinases, including the mitogen-activated protein kinases (MAPKs), calcium calmodulin-dependent protein kinases, Akt/PKB, and the Janus kinases. These kinases phosphorylate a number of transcription factors, increasing their transcriptional activating activity and, in some cases, DNA binding activity. Elevated [Ca2+] can also activate the protein phosphatase, calcineurin,4 which dephosphorylates members of the nuclear factor-activated T cell (NF-AT) family of transcription factors, causing their nuclear translocation. Activated transcription factors bind to specific DNA sequences …
43. Activation of β-catenin signaling pathways by classical G-protein-coupled receptors: Mechanisms and consequences in cycling and non-cycling cells
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Sergey P. Shevtsov, Thomas Force, and Syed Haq
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G protein ,Myocardium ,Wnt signaling pathway ,LRP6 ,LRP5 ,macromolecular substances ,Cell Biology ,Biology ,Receptors, G-Protein-Coupled ,Cell biology ,Wnt Proteins ,Catenin ,Heterotrimeric G protein ,Animals ,Humans ,Myocytes, Cardiac ,Receptor ,Molecular Biology ,beta Catenin ,Signal Transduction ,Developmental Biology ,G protein-coupled receptor - Abstract
Wnt signaling pathways are some of the most intensely studies in all of biology. Recently, a number of classical heterotrimeric G protein coupled receptors (GPCRs) have been shown to activate the canonical Wnt pathway, culminating in the stabilization of beta-catenin and induction of transcription of genes regulated by the Tcf/Lef family of transactivators. However, mechanisms by which these GPCRs accomplish this differ in key ways, and in some circumstances, the phenotypes produced are novel. Herein, we will examine mechanisms by which classical GPCRs interact with the canonical Wnt pathway, culminating in its activation, and describe the consequences of this activation, focusing on the heart. In the heart, the contractile cells, or cardiomyocytes, are terminally differentiated and virtually exclusively grow by increasing cell size (hypertrophy) rather than cell number, and we will describe how GPCR-mediated activation of the canonical pathway can drive this process.
44. IMMUNOLOGICAL EVALUATION OF FORMULATED DRUGS AGAINST TYPHOID
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syed haque
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Typhoid ,Nitric oxide (NO) ,DTH ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Objectives: Typhoid fever an important causes of illness and death, particularly among children and adolescents in south-central and Southeast Asia, where enteric fever is associated with poor sanitation and unsafe food and water. Cell-mediated immunity (CMI) plays an important role for the survival of the host in experimental salmonellosis. Nitric oxide (NO) is the one of the product of macrophages activated by cytokines, microbial compounds or both, is derived from the amino acid L-arginine by the enzymatic activity of inducible nitric oxide synthase (iNOS or NOS2) which acts as antimicrobial molecule. Results and Conclusions: The results of the present study showed that the induction of DTH reaction in the animals treated with L-Arg, ciprofloxacin and their combination followed by immunization with S. typhimurium cell lysate using an antigen revealed that the treatment with combination increased foot pad swelling significantly as compared to saline treated control animals at 48 hour which was followed by a decrease of the swelling at 72 hour.
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- 2014
45. Role of nitric oxide and reduced glutathione and their implication on typhoid
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Syed Haque
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Nitric oxide ,Reduced glutathione (GSH) ,Typhoid ,Biology (General) ,QH301-705.5 - Abstract
Typhoid one of the most important causes of illness and death, particularly among children and adolescents in south-central and Southeast Asia, due to poor sanitation and unsafe food and drinking water. Nitric oxide (NO) is a versatile molecules produced in a biological system. Reduced glutathione (GSH) is the most abundant cytosolic thiol that easily reacts with NO and forms S-nitrosoglutathione (GS-NO) these thiol compounds might decrease the levels of free forms of NO, thereby affecting its fate and biological activity. Infection with bacteria to control mice resulted in significant decrease in the GSH level by 10% at day 8 of infection and after treatment with formulated drugs significant increment was observed.
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- 2012
46. Electronic Medical Record Tobacco Use Vital Sign
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John W. NorrisIII, Smita Namboodiri, Syed Haque, David J. Murphy, and Frank Sonneberg
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tobacco ,vital sign ,electronic ,record ,Diseases of the respiratory system ,RC705-779 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective Determination of the prevalence of tobacco use and impact of tobacco prevention/treatment efforts in an electronic medical record enabled practice utilizing a defined tobacco vital sign variable. Design and Measurements Retrospective cohort study utilizing patient data recorded in an electronic medical record database between July 15, 2001, and May 31, 2003. Patient-reported tobacco use status was obtained for each of 6,771 patients during the pre-provider period of their 24,824 visits during the study period with the recorder blinded to past tobacco use status entries. Results An overall current tobacco use prevalence of 27.1% was found during the study period. Tobacco use status was recorded in 96% of visits. Comparison of initial to final visit tobacco use status demonstrates a consistency rate of 75.0% declaring no change in tobacco status in the 4,522 patients with two or more visits. An 8.6% net tobacco use decline was seen for the practice (p value < 0.001) Conclusion Self reported tobacco use status as a vital sign embedded within the workflow of an electronic medical record enabled practice was a quantitative tool for determination of tobacco use prevalence and a measuring stick of risk prevention/intervention impact.
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- 2004
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47. The β-Catenin/T-Cell Factor/Lymphocyte Enhancer Factor Signaling Pathway Is Required for Normal and Stress-Induced Cardiac Hypertrophy.
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Xin Chen, Shevtsov, Sergei P., Hsich, Eileen, Lei Cui, Syed Haq, Aronovitz, Mark, Kerkelä, Risto, Molkentin, Jeffery D., Liao, Ronglih, Salomon, Robert N., Patten, Richard, and Force, Thomas
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CELL cycle ,TRANSCRIPTION factors ,HEART disease genetics ,HYPERTROPHY ,CELLS - Abstract
In cells capable of entering the cell cycle, including cancer cells, β-catenin has been termed a master switch, driving proliferation over differentiation. However, its role as a transcriptional activator in terminally differentiated cells is relatively unknown. Herein we utilize conditional, cardiac-specific deletion of the β-catenin gene and cardiac-specific expression of a dominant inhibitory mutant of Lef-1 (Lef-1Δ20), one of the members of the T-cell factor/lymphocyte enhancer factor (Tcf/Lef) family of transcription factors that functions as a coactivator with β-catenin, to demonstrate that β-catenin/Tcf/Lef-dependent gene expression regulates both physiologic and pathological growth (hypertrophy) of the heart. Indeed, the profound nature of the growth impairment of the heart in the Lef-1Δ20 mouse, which leads to very early development of heart failure and premature death, suggests β-catenin/Tcf/Lef targets are dominant regulators of cardiomyocyte growth. Thus, our studies, employing complementary models in vivo, implicate β-catenin/Tcf/Lef signaling as an essential growth-regulatory pathway in terminally differentiated cells. [ABSTRACT FROM AUTHOR]
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- 2006
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48. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1.
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Andreucci, Michele, Michael, Ashour, Kramers, Cornelis, Kwon Moo Park, Ang Chen, Matthaeus, Tilman, Alessandrini, Alessandro, Syed Haq, Force, Thomas, Bonventre, Joseph V., Park, Kwon Moo, Chen, Ang, and Haq, Syed
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ISCHEMIA , *KIDNEY diseases , *ADENOSINE triphosphate , *ADENOSINE triphosphate metabolism , *PROTEIN metabolism , *ANIMAL experimentation , *COMPARATIVE studies , *EPITHELIAL cells , *IMMUNOHISTOCHEMISTRY , *KIDNEYS , *RESEARCH methodology , *MEDICAL cooperation , *PHOSPHORYLATION , *RATS , *REPERFUSION injury , *RESEARCH , *RESEARCH funding , *SWINE , *TRANSFERASES , *RENAL circulation , *EVALUATION research - Abstract
Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK[sub 1] cells result in phosphorylation of FKHR and FKHRL1. Background. Cell death and survival pathways are critical determinants of epithelial cell fate after ischemia. Forkhead proteins have been implicated in the regulation of cellular survival. Methods and Results. We have found that none of the forkhead family of proteins, FKHR, is phosphorylated after ischemia/reperfusion in the rat kidney. The time course of phosphorylation is similar to the time course of activation of the forkhead protein kinase Akt/protein kinase B (PKB), with maximal phosphorylation at 24 to 48 hours postreperfusion when the process of regeneration peaks. Extracellular signal-regulated kinase (ERK)1/2 activation has also been implicated as prosurvival in the injured kidney. ERK1/2 were phosphorylated in postischemic kidneys at 5, 30, and 90 minutes of reperfusion, with phosphorylation decreased by 24 and 48 hours. Immunocytochemical analysis revealed increased phospho-ERK1/2 in the thick ascending limb and isolated cells of the S3 segment, which have lost apical actin staining. To understand the relationship between forkhead phosphorylation, Akt, and ERK1/2, an in vitro model of injury was employed. After 40 minutes of chemical anoxia followed by dextrose addition for 20 minutes to replete adenosine triphosphate (ATP) levels, FKHR and FKHRL1 are phosphorylated. The levels of phospho-Akt are increased for at least 120 minutes after dextrose addition with a maximum at 20 minutes. Phosphorylation of Akt, FKHR, and FKHRL1 are phosphatidylinositol 3-kinase (PI 3-kinase) dependent since phosphorylation is reduced by the PI 3-kinase inhibitors, wortmannin, or LY294002. Inhibition of mitogen-activated protein kinase (MAPK)/ERK kinase (MEK1/2), the upstream activator of ERK1/2, has no effect on forkhead protein phosphorylation after chemical anoxia/dextrose addition. Conclusion. We conclude that PI 3-kinase and Akt are activated after renal ischemia/reperfusion and that Akt phosphorylation leads to phosphorylation of FKHR and FKHRL1, which may affect epithelial cell fate in acute renal failure. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
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