tbuckley/cabot-search huggingface dataset:
Sodium-dependent phosphate cotransporter type 1 sequence polymorphisms in male patients with gout
Authors: Wako Urano, Atsuo Taniguchi, Naohiko Anzai, Eisuke Inoue, Yoshikatsu Kanai, Mariko Yamanaka, Hitoshi Endou, Naoyuki Kamatani, Hisashi Yamanaka
Journal: Annals of the Rheumatic Diseases (2009)

Objectives Molecular biological approaches have recently identified urate transporters in renal proximal tubular cells. Human sodium-dependent phosphate cotransporter type 1 encoded by SLC17A1 is a urate transporter localised to the renal proximal tubular cells and candidate molecule to secret urate from renal tubular cells to urine. This study investigated the roles of SLC17A1 in the development of gout. Patients and Methods Single nucleotide polymorphisms in the human SLC17A1 gene (rs1165176, rs1165151, rs1165153, rs1165196, rs1165209, rs1165215, rs1179086, rs3799344 and rs3757131) were selected, and an association study was conducted using male patients with gout (n=175) and male controls (n=595). Results There were significant differences between gout and control groups in the distribution of genotypes at rs1165196 (T806C; Ile269Thr, odds ratio (OR) 0.55, p=0.0035), rs1179086 (OR 0.57, p=0.0018) and rs3757131 (OR 0.54, p=0.0026). In controls, T806C alone had no effect on serum uric acid (sUA) levels. However, T806C showed significant interaction with a reduction of sUA in obese individuals (body mass index ≥25) using multiple regression analysis. Conclusions Our data suggest that SLC17A1 polymorphisms are associated with the development of gout.
Acute Kidney Injury in Older Adults
Authors: Sharon Anderson, Basil Eldadah, Jeffrey B. Halter, William R. Hazzard, Jonathan Himmelfarb, Frances McFarland Horne, Paul L. Kimmel, Bruce A. Molitoris, Mahadev Murthy, Ann M. O'Hare, Kenneth E. Schmader, Kevin P. High
Journal: Journal of the American Society of Nephrology (2011)

Aging kidneys undergo structural and functional changes that decrease autoregulatory capacity and increase susceptibility to acute injury. Acute kidney injury associates with duration and location of hospitalization, mortality risk, progression to chronic kidney disease, and functional status in daily living. Definition and diagnosis of acute kidney injury are based on changes in creatinine, which is an inadequate marker and might identify patients when it is too late. The incidence of acute kidney injury is rising and increases with advancing age, yet clinical studies have been slow to address geriatric issues or the heterogeneity in etiologies, outcomes, or patient preferences among the elderly. Here we examine some of the current literature, identify knowledge gaps, and suggest potential research questions regarding acute kidney injury in older adults. Answering these questions will facilitate the integration of geriatric issues into future mechanistic and clinical studies that affect management and care of acute kidney injury.
Activated Protein C Resistance and Factor V Leiden Mutation Are Independent Risk Factors for Venous Thromboembolism
Authors: F Rodeghiero, A Tosetto
Journal: Annals of Internal Medicine (1999)

Background: Resistance to activated protein C due to the factor V R506Q (Leiden) mutation is the most common clotting abnormality in patients with venous thromboembolism. Objective: To evaluate the risk for venous thromboembolism associated with the factor V Leiden mutation or with resistance to activated protein C in the general population. Design: Cross-sectional survey. Setting: General community of Vicenza, Italy. Patients: A population-based sample of 15 109 white persons 18 to 65 years of age who were randomly selected from the census list. Measurements: Sequential validated approach based on participants' reports and Doppler ultrasonography. Resistance to activated protein C was investigated in all participants; 2134 participants with resistance to activated protein C were screened for the factor V Leiden mutation. Results: Carriers of the factor V Leiden mutation had a relative risk of 3.3 (95% CI, 1.7 to 6.1) for venous thromboembolism before 65 years of age. The fraction of cases attributable to the factor V Leiden mutation was 6.6%. By 65 years of age, 5.7% of carriers of the mutation had had venous thromboembolism, mostly after surgery. Participants with a reduced response to activated protein C were at higher risk even if they did not carry the mutation (odds ratio, 1.7 [CI, 1.0 to 2.7]); the attributable risk for venous thromboembolism was 5.1%. Conclusions: The factor V Leiden mutation and resistance to activated protein C are important, independent risk factors for venous thromboembolism. Screening strategies for the factor V Leiden mutation in patients undergoing surgery or experiencing major trauma cannot be recommended, but phenotypic evaluation of resistance to activated protein C should be encouraged in patients with venous thromboembolism.
Mitochondrial ROMK Channel Is a Molecular Component of MitoK <sub>ATP</sub>
Authors: D. Brian Foster, Alice S. Ho, Jasma Rucker, Anders O. Garlid, Ling Chen, Agnieszka Sidor, Keith D. Garlid, Brian O'Rourke
Journal: Circulation Research (2012)

Rationale: Activation of the mitochondrial ATP-sensitive potassium channel (mitoK ATP ) has been implicated in the mechanism of cardiac ischemic preconditioning, yet its molecular composition is unknown. Objective: To use an unbiased proteomic analysis of the mitochondrial inner membrane to identify the mitochondrial K + channel underlying mitoK ATP . Methods and Results: Mass spectrometric analysis was used to identify KCNJ1(ROMK) in purified bovine heart mitochondrial inner membrane and ROMK mRNA was confirmed to be present in neonatal rat ventricular myocytes and adult hearts. ROMK2, a short form of the channel, is shown to contain an N-terminal mitochondrial targeting signal, and a full-length epitope-tagged ROMK2 colocalizes with mitochondrial ATP synthase β. The high-affinity ROMK toxin, tertiapin Q, inhibits mitoK ATP activity in isolated mitochondria and in digitonin-permeabilized cells. Moreover, short hairpin RNA—mediated knockdown of ROMK inhibits the ATP-sensitive, diazoxide-activated component of mitochondrial thallium uptake. Finally, the heart-derived cell line, H9C2, is protected from cell death stimuli by stable ROMK2 overexpression, whereas knockdown of the native ROMK exacerbates cell death. Conclusions: The findings support ROMK as the pore-forming subunit of the cytoprotective mitoK ATP channel.
Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160
Authors: Josef S Smolen, Jonathan Kay, Robert B M Landewé, Eric L Matteson, Norman Gaylis, Jurgen Wollenhaupt, Frederick T Murphy, Yiying Zhou, Elizabeth C Hsia, Mittie K Doyle
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. <h3>Methods</h3> Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with &lt;20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported. <h3>Results</h3> 459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 (≥20% improvement in American College of Rheumatology criteria) response and ≥0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70–73% and 75–81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement ≥0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively. <h3>Conclusion</h3> In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in ∼57–67% of patients who continued treatment. Golimumab safety was consistent with other anti-TNF agents, although definitive conclusions regarding long-term safety require further monitoring.
Gender differences in plantar loading during three soccer-specific tasks
Authors: E L Sims, W M Hardaker, R M Queen
Journal: British Journal of Sports Medicine (2008)

Objective: Examine the effect of gender on plantar loading during three football-specific tasks. Design: Thirty-four athletes (17 men, 17 women) ran an agility course five times while wearing the Nike Vitoria hard ground cleat. Plantar loading data were recorded during a side cut, a cross-over cut and a forward acceleration task using Pedar-X insoles. Setting: Controlled laboratory study. Participants: No history of lower extremity injury in the past 6 months, no previous foot or ankle surgery, not currently wearing foot orthotics and play a cleated sport at least two times per week. Main outcome measurements: Contact area, maximum force and the force-time integral (FTI) in the medial and lateral midfoot, medial, middle and lateral forefoot as well as the hallux. A univariate ANCOVA (α = 0.05) was performed on each dependent variable (covariate was course speed). Results: Significant gender differences existed in the force and force-time integral beneath the lateral midfoot and forefoot during the cross-over cut task as well as in the middle forefoot during the side cut task with the men demonstrating an increased force. No significant differences existed in the loading on the medial side of the foot during any tasks. Conclusions: The results of this study indicate that the increase in plantar loading on the lateral portion of the midfoot and forefoot in men could be one possible explanation for the increased incidence of fifth metatarsal stress fractures in men. Gender differences in loading patterns need to be considered when comparing different movements as well as different footwear conditions.
Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3).
Authors: R Bakimer, P Fishman, M Blank, B Sredni, M Djaldetti, Y Shoenfeld
Journal: Journal of Clinical Investigation (1992)

Antiphospholipid syndrome (APLS) is characterized by thrombocytopenia, thromboembolic phenomena, and recurrent fetal loss, associated with anticardiolipin antibodies (ACA) and/or lupus anticoagulant. The syndrome may be primary or may be associated with other conditions such as systemic lupus erythematosus. We have previously shown the ability to induce APLS in naive mice following passive transfer of serum and monoclonal ACAs. Similarly we generated the secondary APLS in BALB/c mice following immunization with a pathogenic anti-DNA antibody. In the current study we report on the induction of primary APLS following immunization of BALB/c mice with a human monoclonal ACA (H-3). The mice developed high persistent titers of ACA. The APLS was characterized by prolonged activated partial thromboplastin time, low fecundity rate (21% vs. 48% of control immunized mice), high resorption index of fetuses (25% vs. 3%), and low weights of embryos and placentae. Our study points to the ability of inducing primary APLS in naive mice. The induction of various presentations of APLS by different ACA may explain the diversity of clinical manifestations seen in patients with APLS.
A Prospective Institutional Study of Chemoradiotherapy with Weekly Docetaxel for Unresectable Locally Advanced Esophageal Carcinoma
Authors: Singhal Mukesh, Kapoor Akhil, Bagri Puneet, Singh Daleep, Narayan Satya, Nirban Raj, Singh Guman, Maharia Sitaram, Jakhar Shankar, Beniwal Surender, Kumari Pramila, Sharma Neeti, Kumar Harvindra, Sharma Ajay, Bardia Megh
Journal: Annals of Oncology (2014)
GLOMERULAR PERMEABILITY
Authors: Richard C. Graham, Morris J. Karnovsky
Journal: The Journal of Experimental Medicine (1966)

1. Glomerular permeability was studied by ultrastructural cytochemistry, using as protein tracers two intravenously injected peroxidases of differing molecular weight. 2. Horseradish peroxidase (molecular weight 40,000) passed rapidly through the endothelial fenestrae, across the basement membrane, and through the epithelial slits into the urinary space. Human myeloperoxidase (molecular weight 160,000 to 180,000) also passed rapidly through the endothelial fenestrae and across the basement membrane, but was impeded at the level of the epithelial slits. Both proteins were taken up in large amounts by the mesangial cells. 3. The present findings indicate that the epithelial slits are the primary filtration barrier responsible for the differential permeability to proteins of varying molecular size. 4. The observations also support the concept that an important function of the mesangial cells is the incorporation and disposal of glomerular filtration residues.
Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials
Authors: Jon L Pryor, Stanley E Althof, Christopher Steidle, Raymond C Rosen, Wayne JG Hellstrom, Ridwan Shabsigh, Maja Miloslavsky, Sherron Kell
Journal: The Lancet (2006)
The courts' role in decisions about medical treatment
Authors: L. Oates
Journal: BMJ (2000)

<h3>Objective</h3> To estimate the national prevalence and racial/ethnic differences in psychiatric diagnoses and pharmacologic treatment in a US Medicaid beneficiary population of youth with systemic lupus erythematosus (SLE). <h3>Methods</h3> We included youth aged 10 to 18 years with a diagnosis of SLE (defined as ≥ 3 outpatient visit claims with an International Classification of Diseases, 9th ed. code of 710.0, each &gt; 30 days apart) in the US Medicaid Analytic Extract database from 2006 and 2007. This database contains all inpatient and outpatient Medicaid claims from 49 states and the District of Columbia. We calculated the prevalence of psychiatric diagnoses and treatment, and used logistic regression to compare depression and anxiety diagnoses, antidepressant, and anxiolytic use among racial/ethnic groups. <h3>Results</h3> Of 970 youth with SLE, 15% were white, 42% were African American, 27% were Latino, and 16% were of other races/ethnicities. Diagnoses of depression were present for 19%, anxiety for 7%, acute stress/adjustment for 6%, and other psychiatric disorders for 18%. Twenty percent were prescribed antidepressants, 7% were prescribed anxiolytics, 6% were prescribed antipsychotics, and 5% were prescribed stimulants. In adjusted analyses, African Americans were less likely than whites to be diagnosed with depression (OR 0.56, 95% CI 0.34–0.90) or anxiety (OR 0.49, 95% CI 0.25–0.98), or to be prescribed anxiolytics (OR 0.23, 95% CI 0.11–0.48). <h3>Conclusion</h3> We present population-level estimates showing high psychiatric morbidity in youth with SLE, but less prevalent diagnosis and treatment in African Americans. Mental health interventions should address potential racial/ethnic disparities in care.
Seasonal Variations in Mood and Behavior Among Chinese Medical Students
Authors: Ling Han, Keqin Wang, Zhaoyun Du, Yiren Cheng, Julie S. Simons, Norman E. Rosenthal
Journal: American Journal of Psychiatry (2000)

The goal of this study was to estimate the frequency of seasonal variations in mood and behavior among Chinese medical students.A total of 1,358 medical students were surveyed with Chinese versions of the Seasonal Pattern Assessment Questionnaire and the Beck Depression Inventory in Jining, China.The mean global seasonality score was 8.3 (SD=3.6) out of a possible 24; 81.7% (N=1,110) of the subjects reported some trouble adapting to changing seasons. Summer difficulties were more common than winter difficulties by a ratio of 3:2; estimated rates of summer seasonal affective disorder and subsyndromal seasonal affective disorder were 4.4% and 8.0%, respectively, compared with corresponding winter rates of 2.4% and 5.7%.These results suggest that seasonal variations in mood and behavior are common in China. The predominance of summer difficulties stands in contrast to that in most Western studies and is consistent with the only other published study performed in Asia.
Autologous Stem Cell Transplantation in Follicular Lymphoma: a Systematic Review and Meta-analysis
Authors: M. Al Khabori, J. R. de Almeida, G. H. Guyatt, J. Kuruvilla, M. Crump
Journal: JNCI Journal of the National Cancer Institute (2011)

The impact of high-dose therapy and autologous stem cell transplantation (ASCT) vs conventional-dose chemotherapy in the initial management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. We performed a systematic review of the randomized clinical trials addressing this question.We searched MEDLINE, EMBASE, CENTRAL, American Society of Hematology, American Society of Clinical Oncology, BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries, and bibliographies of relevant studies for randomized clinical trials comparing myeloablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced FL. We performed a meta-analysis using random effects models to estimate overall survival, event-free survival, and risks of adverse outcomes. Statistical heterogeneity was calculated by using the I(2) statistic.Seven trials proved eligible, four of which provided data from 941 patients that could be included in a meta-analysis and three of which remain unpublished. In two of the trials, patients in both arms received rituximab during the induction treatment. Moderate quality evidence from the three trials that reported overall survival (n = 701 patients) suggests that ASCT did not result in improved overall survival (hazard ratio of death = 0.99, 95% confidence interval [CI] = 0.73 to 1.33). Low-quality evidence from the four trials of 941 patients suggests improvement in event-free survival in favor of ASCT (hazard ratio of death = 0.54, 95% CI = 0.36 to 0.82) with substantial heterogeneity (I(2) = 80%). Adverse outcomes of treatment-related mortality, myelodysplastic syndrome, acute myeloid leukemia, and solid tumors were not different between the two arms (relative risk [RR] of treatment-related mortality = 1.04, 95% CI = 0.29 to 3.70; RR of myelodysplastic syndrome/acute myeloid leukemia = 2.19, 95% CI = 0.45 to 10.55; I(2) = 48%; and RR of solid tumors = 1.30, 95% CI = 0.33 to 5.08). The absolute risk of death from treatment was 14 per 1000 patients for those who received chemotherapy and 15 per 1000 for those who received ASCT (range = 4-52).Available evidence suggests that high-dose therapy and ASCT as part of FL initial treatment does not improve overall survival. Future trials of ASCT in the context of current chemoimmunotherapy approaches to FL are needed.
Evidence for gene conversion among immunoglobulin heavy chain variable region genes.
Authors: S H Clarke, S Rudikoff
Journal: The Journal of Experimental Medicine (1984)

We have previously reported that the VH region amino acid sequence of a phosphocholine (PC)-binding hybridoma antibody of CBA/J origin, HP101 6G6 (6G6), differs extensively from the VH regions of other PC-binding antibodies. The sequence of 6G6 VH appears to be derived from a gene homologous to the BALB/c V11 gene, a member of the PC VH (T15 VH) gene family not normally used to encode PC-binding antibodies. The 6G6 VH sequence differs from the translated sequence of V11 by six amino acids, four of which occur at the same position in other members of this gene family. This coincidence led to the proposal that the 6G6 VH gene was derived by gene conversion involving three genes of the PC VH gene family. We report here the nucleic acid sequence of the rearranged VH gene of hybridoma 6G6. This sequence supports our previous suggestion of gene conversion by confirming those differences, relative to the BALB/c V11 gene sequence, that are encoded by other members of this gene family, and extends this correlation to include three silent base pair substitutions as well. In addition, 5' noncoding region sequence and Southern blot analysis using probes derived from the coding and 5' noncoding regions confirm that the 6G6 VH gene is likely to be derived from the V11 homologue in CBA/J mice, and suggest that all three genes believed to be involved in the generation of the 6G6 VH gene are present in the CBA/J genome, a prerequisite for their involvement in gene conversion.
Hostile takeover: fungal protein promotes host cell invasion
Authors: J. Andrew Alspaugh
Journal: Journal of Clinical Investigation (2013)

The ability to suppress the immune system has lead to great advances in transplant technology and treatment of autoimmune diseases. Unfortunately, the immunosuppression of these patients has led to the rise of opportunistic infections by organisms that are recalcitrant to current prophylactic strategies. One such example is the increase of mucormycosis, an invasive infection caused by filamentous fungi of the order Mucorales. In this issue of the JCI, Gebremariam and colleagues determined that spore coat homolog (CotH) proteins are required for angioinvasion and that these proteins are unique to Mucorales. Their findings provide a potential therapeutic target for prevention and treatment of mucormycosis.
Prediction of response to anticancer treatment as simple as the resolution of ordinary differential equations?
Authors: Pierre Laurent-Puig, Gilles Manceau, Valérie Boige, Hélène Blons
Journal: Gut (2011)

The introduction of differential equations in medicine is due to the Swiss physician mathematician, Daniel Bernoulli (1700–1782), who calculated the survival gain of the population by the generalisation of smallpox virus inoculation.1 Many models in systems biology are described as systems of ordinary differential equations, which consist of establishing series of mathematical relationships that describe the sequential changes in components of the systems over time.2 Programmed cell death, apoptosis, can be activated through two different pathways: the death receptor or extrinsic pathway, engaged by members of the tumour necrosis factor (TNF) receptor family on the cell surface; and the Bcl-2-regulated mitochondrial (B-cell lymphoma 2) or intrinsic pathway. The intrinsic pathway starts with BH3-only protein induction or post-translational activation, which results in inactivation of some BCL-2 family members. This relieves inhibition of BAX(BCL2-associated X protein) and BAK (BCL2-antagonist/killer 1) activation, which in turn promotes apoptosis through induction of permeabilisation of the outer mitochondrial membrane and subsequent release of apoptogenic molecules, such as cytochrome c and DIABLO (IAP-binding mitochondrial protein). Cytochrome c binds to APAF1 (apoptotic peptidase …
Gonococcal Urethritis in Males in Vietnam
Authors: L. Herbert Maurer
Journal: JAMA (1969)

Four hundred men with culturally proved gonococcal urethritis were treated with four antibiotic programs. Treatment with 2.4 million units of procaine penicillin G on two consecutive days resulted in a 25% failure rate, while treatment with 2.4 million units of procaine penicillin G twice plus 2.4 million units of penicillin G benzathine showed a 9.3% failure rate. Patients treated with probenecid plus 2.4 million units of procaine penicillin G had a 7.6% failure rate, and those treated with tetracycline hydrochloride had a 7.1% failure rate.