tbuckley/cabot-search huggingface dataset:
Lysine acetylation induced by chronic ethanol consumption impairs dynamin-mediated clathrin-coated vesicle release
Authors: Blythe D. Shepard, Dean J. Tuma, Pamela L. Tuma
Journal: Hepatology (2011)

The liver is the major site of ethanol metabolism and thus sustains the most injury from chronic alcohol consumption. Ethanol metabolism by the hepatocyte leads to the generation of reactive metabolites and oxygen radicals that can readily adduct DNA, lipids, and proteins. More recently, it has become apparent that ethanol consumption also leads to increased post-translational modifications of the natural repertoire, including lysine hyperacetylation. Previously, we determined that alcohol consumption selectively impairs clathrin-mediated internalization in polarized hepatocytes. However, neither the step at which the block occurs nor the mechanism responsible for the defect have been identified. To identify the specific step at which clathrin-mediated internalization is impaired, we examined the distributions, levels, and assembly of selected components of the clathrin machinery in control and ethanol-treated cells. To determine whether the impairment is caused by ethanol-induced lysine acetylation, we also examined the same coat components in cells treated with trichostatin A (TSA), a deacetylase inhibitor that leads to protein hyperacetylation in the absence of ethanol.We determined that both ethanol and TSA impair internalization at a late stage before vesicle fission. We further determined that this defect is likely the result of decreased dynamin recruitment to the necks of clathrin-coated invaginations resulting in impaired vesicle budding. These results also raise the exciting possibility that agents that promote lysine deacetylation may be effective therapeutics for the treatment of alcoholic liver disease.
Diabetes segregates as a single locus in crosses between inbred BB rats prone or resistant to diabetes.
Authors: H Markholst, S Eastman, D Wilson, B E Andreasen, A Lernmark
Journal: The Journal of Experimental Medicine (1991)

Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling type 1 diabetes mellitus in man. They also exhibit lifelong T cell deficiency. The segregation of both diabetes and lymphopenia was studied in crosses between this inbred line of rats and the related but nondiabetic and nonlymphopenic inbred diabetes-resistant (DR) BB rat line. Diabetes segregated as a single, autosomal recessive trait and was always accompanied by lymphopenia. Among the limited number of differences in the genomic DNA sequences of the two lines, DP and DR BB, one may account for the development of diabetes and lymphopenia in the DP BB rats. It may be possible to screen the genomic DNA for such differences to detect a marker for the phenotypes.
Enhanced Expression of Hepatocyte Growth Factor by Pulmonary Ischemia–Reperfusion Injury in the Rat
Authors: TAKATSUGU YAMADA, MICHIYOSHI HISANAGA, YOSHIYUKI NAKAJIMA, SHINYA MIZUNO, KUNIO MATSUMOTO, TOSHIKAZU NAKAMURA, HIROSHIGE NAKANO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Hepatocyte growth factor (HGF) has recently been noted to function as a pulmotrophic factor for lung regeneration. The present study was conducted to determine if HGF would be induced in a rat model of pulmonary ischemia–reperfusion (IR) injury, which was established by occlusion of the left lung, and to examine the significance of HGF in subsequent lung repair. The sham-operated rats underwent simple thoracotomy in which the lung was not clamped. We measured the plasma and the tissue levels of HGF by enzyme-linked immunosorbent assays, and the expression of HGF mRNA by Northern blotting. The plasma HGF level was markedly elevated after pulmonary ischemia and reached the peak value on the third postoperative day, being 5-fold higher than that of the sham-operated rats. HGF mRNA expression and the tissue HGF levels were augmented twofold in the ischemic reperfused lung. Immunohistochemical analysis revealed that the infiltrating alveolar macrophages were intensely stained for HGF. DNA synthesis of alveolar epithelial cells, as identified by proliferating cell nuclear antigen (PCNA) staining, was 3-fold higher in the reperfused lung than in the sham-operated lung. Notably, HGF-neutralizing treatment with an anti-HGF antibody reduced DNA synthesis of alveolar epithelial cells in the reperfused lung and aggravated lung injury. This study shows that HGF was induced in the ischemic reperfused lung and may play an important role in regeneration of an injured lung after pulmonary IR.
One million people to have personal care budgets by 2013
Authors: A. O'Dowd
Journal: BMJ (2010)

The government has announced plans to transform social care funding by giving around one million older people, people with a disability, and their carers a personal care budget by 2013. A greater emphasis on personal choice and greater cooperation between local government and the NHS is at the heart of the Department of Health’s plans unveiled this week. Health minister Paul Burstow made several announcements including:
The APOBEC3 Cytidine Deaminases: An Innate Defensive Network Opposing Exogenous Retroviruses and Endogenous Retroelements
Authors: Ya-Lin Chiu, Warner C. Greene
Journal: Annual Review of Immunology (2008)

All retroviruses, including HIV-1, display species-specific patterns of infection. The impaired growth of these retroviruses in foreign and sometimes even in their natural hosts often stems from the action of potent host-encoded “viral restriction factors” that form important protective components of the innate immune system. The discovery of APOBEC3G and related cytidine deaminases as one class of host restriction factors and of the action of HIV-1 Vif as a specific APOBEC3G antagonist have stimulated intense scientific interest. This Vif-APOBEC3G axis now forms a very attractive target for development of an entirely new class of anti-HIV drugs. In this review, we summarize current understanding of the mechanism of action of the APOBEC3 family of enzymes, their intriguing regulation within cells, the impact of these enzymes on viral evolution and disease progression, and their roles in controlling not only the replication of exogenous retroviruses but also the retrotransposition of endogenous retroelements.
Effectiveness and cost-effectiveness of interferon beta and glatiramer acetate in the UK Multiple Sclerosis Risk Sharing Scheme at 6 years: a clinical cohort study with natural history comparator
Authors: Jacqueline Palace, Martin Duddy, Thomas Bregenzer, Michael Lawton, Feng Zhu, Mike Boggild, Benjamin Piske, Neil P Robertson, Joel Oger, Helen Tremlett, Kate Tilling, Yoav Ben-Shlomo, Charles Dobson
Journal: The Lancet Neurology (2015)
Cancer Screening before and after Switching to a High-Deductible Health Plan
Authors: J. Frank Wharam, Alison A. Galbraith, Ken P. Kleinman, Stephen B. Soumerai, Dennis Ross-Degnan, Bruce E. Landon
Journal: Annals of Internal Medicine (2008)

Background: Health plans with high deductibles could lead patients to avoid preventive care, such as cancer screening. Objective: To determine the effect of membership in a high-deductible health plan on cervical, breast, and colorectal cancer screening. Design: Before–after comparison between groups. Setting: A high-deductible health plan and an HMO in Massachusetts. The high-deductible health plan fully covered mammography, Papanicolaou tests, and fecal occult blood testing (FOBT) but not colonoscopy, flexible sigmoidoscopy, or double-contrast barium enema (DCBE). Participants: 3169 high-deductible health plan members and 27 022 HMO members (who served as controls). Measurements: Change in the proportions of patients undergoing breast, cervical, and colorectal cancer screening. Results: Cancer screening in the high-deductible health plan group was unchanged from baseline to follow-up (adjusted ratios of change, 1.04 [95% CI, 0.91 to 1.19] for breast cancer, 1.04 [CI, 0.92 to 1.17] for cervical cancer, and 1.02 [CI, 0.89 to 1.16] for colorectal cancer). High-deductible health plan members had colonoscopy, flexible sigmoidoscopy, and DCBE less often (ratio of change, 0.73 [CI, 0.56 to 0.95]) and FOBT more often (ratio of change, 1.16 [CI, 1.01 to 1.33]) than HMO members. Limitations: Population screening frequency was probably underestimated because the study could not assess screening before the baseline year. The study may have included people ineligible for screening because of previous colectomy, mastectomy, or hysterectomy. The findings are limited to a population with relatively high socioeconomic status, which is typical of employed, commercially insured populations. Conclusion: Members of a high-deductible health plan did not seem to change their use of breast, cervical, and colorectal cancer screening when tests were fully covered. However, members may have substituted a fully covered screening test (FOBT) for tests subject to the deductible (colonoscopy, flexible sigmoidoscopy, and DCBE).
Corticosteroid-induced clinical adverse events: frequency, risk factors and patient?s opinion
Authors: L. Fardet, A. Flahault, A. Kettaneh, K.P. Tiev, T. Généreau, C. Tolédano, C. Lebbé, J. Cabane
Journal: British Journal of Dermatology (2007)

More than 50 years after the introduction of corticosteroids, few studies have focused on corticosteroid-induced adverse events after long-term systemic therapy.To assess the frequency, risk factors and patient's opinion regarding clinical adverse events occurring early during prednisone therapy.We conducted a cohort study in two French centres. All consecutive patients starting long-term (> oir = 3 months), high dosage (> or = 20 mg day(-1)) prednisone therapy were enrolled. The main clinical adverse events attributable to corticosteroids were assessed after 3 months of therapy, by comparison with baseline status. The patient's opinion regarding the disability induced by these adverse events was recorded. Risk factors of frequently observed adverse effects were identified by using logistic regression.Eighty-eight patients were enrolled and 80 were monitored for at least 3 months (women 76%; mean age 59.1 +/- 18.7 years; giant cell arteritis 39%; mean baseline prednisone dosage 54 +/- 17 mg day(-1)). Lipodystrophy was the most frequent adverse event [63.0% (51.0-73.1)], was considered the most distressing by the patients and was most frequent in women and young patients. Neuropsychiatric disorders occurred in 42 patients [52.5% (41.0-63.8)], necessitating hospitalization in five cases. Skin disorders were noted by 37 patients [46.2% (35.0-57.7)] and were more frequent in women. Muscle cramp and proximal muscle weakness were reported by 32.5% (22.5-43.9) and 15% (8.0-24.7) of patients, respectively. Newly developed hypertension occurred in 8.7% (2.9-20.3) of patients. Lastly, 39% (19.7-61.4) of the premenopausal women reported menstrual disorders.Lipodystrophy and neuropsychiatric disorders are common adverse events of long-term prednisone therapy and are particularly distressing for the patients concerned. The impact of these adverse events on adherence to corticosteroid therapy is not known.
Next-generation sequencing: comprehensive genetic testing for epidermolysis bullosa
Authors: E.G. Pfendner
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 731 In this issue of the BJD, Tenedini et al.1 report on diagnostic testing for epidermolysis bullosa (EB) using both a polymerase chain reaction‐directed library‐generation approach that targets 34 selected EB candidate genes, and next‐generation sequencing (NGS) technology. EB is a complex disorder, with an ever‐expanding list of genes known to harbour mutations associated with the phenotype. The primary characteristic is skin blistering with little trauma that may cover large portions of the body or may be restricted to smaller areas such as the hands and feet. The phenotypic spectrum is broad, and some patients have extensive blistering of the skin and mucous membranes, which may compromise the airway and result in demise in the neonatal period. Additionally, some forms result in deformities due to scarring, pyloric atresia or muscular dystrophy. The list of EB types and the associated genes is now at 18, with new varieties appearing frequently.2 Until recently, genetic testing was a multistep process starting with a skin biopsy to define the cleavage plane in the affected tissue and to narrow down the list of genes to sequence. The stepwise sequencing approach could take many months to identify the causative mutation. In approximately 5–15% of cases, mutations are not identified by this approach.3,4,5 In addition the cost of sequencing multiple genes could run quite high and be out of reach for many patients and laboratories. NGS is the new approach to gene sequencing and can be used to cover a large gene panel or, if needed, the entire exome in one step and more quickly than sequential gene testing for EB.
Dihydrotachysterol: a calcium active steroid not dependent upon kidney metabolism
Authors: Harold E. Harrison, Helen C. Harrison
Journal: Journal of Clinical Investigation (1972)

The activity of dihydrotachysterol and cholecalciferol was determined in nephrectomized or sham-operated vitamin D-depleted rats using in vitro transport of calcium and phosphate by everted intestinal preparations as the index of physiologic response. The activity of dihydrotachysterol was not reduced by absence of the kidneys whereas that of cholecalciferol was markedly inhibited so that at least a 10-fold greater dose of the latter was necessary to produce an equivalent effect in the nephrectomized rat as in the control. Dihydrotachysterol is therefore equipotent with cholecalciferol in the anephric rat although much less active in the intact animal.
Inhibition of IL-1β Mediated Proinflammatory Cytokine Production by Epigallocatechin Gallate in Human Alveolar Epithelial Cells
Authors: Oluwakemi Phillips, Ruan R. Cox, Jutaro Fukumoto, Itsuko Fukumoto, Prasanna Tamarapu, Tran Luong, Richard F. Lockey, Narasaiah Kolliputi
Journal: Journal of Allergy and Clinical Immunology (2013)
Cross-reactivity between C-reactive protein and idiotypic determinants on A phosphocholine-binding murine myeloma protein.
Authors: J E Volanakis, J F Kearney
Journal: The Journal of Experimental Medicine (1981)

Binding of human 125I-C-reactive protein (CRP) to sheep erythrocytes sensitized with pneumococcal C polysaccharide (E-PnC) was found to be Ca++ dependent and inhibitable by phosphocholine, CRP, and HOPC 8. Binding of 125I-HOPC 8 to EPnC was Ca++ -independent but could also be inhibited by phosphocholine, CRP, and HOPC 8. Thus, CRP and HOPC 8, despite a differential Ca++ requirement, share a common binding specificity for phosphocholine. A monoclonal anti-idiotypic antibody (MAB), GB4-10, prepared in A/J mice immunized with BALB/c HOPC 8 inhibited the binding of both 125I-CRP and 125I-HOPC 8 to E-PnC. In addition, both proteins bound to GB4-10 immobilized on polysterene tubes. Interestingly, binding of 125I-CRP to GB4-10 required Ca++. Similar results were also obtained with another MAB (AB1-2) prepared similarly to GB4-10, whereas neither protein bound to a control MAB (EB3-7) against an alpha1 leads to 3 dextran-binding myeloma protein, J558. Binding of 125I-HOPC 8 to GB4-10 could be inhibited by HOPC 8, keyhole limpet hemocyanin-phosphocholine but not phosphocholine but not phosphocholine, and in the presence of Ca++ by CRP. These data indicate that CRP bears antigenic determinants cross-reacting with certain idiotypic determinants on HOPC 8. They also suggest that Ca++ acts as an allosteric effector, perhaps stabilizing the phosphocholine-binding site of CRP.
A 27-Year-Old Woman With a Diagnosis of Polycystic Ovary Syndrome
Authors: Richard S Legro
Journal: JAMA (2007)

Ms R, a 27-year-old woman with polycystic ovary syndrome (PCOS) diagnosed after irregular menses, hirsutism, and polycystic ovaries, is concerned about weight gain despite regular exercise and watching her diet. Prescribed oral contraceptives to regulate her menses and help reduce her androgen levels, she wants to know the alternatives for treatment of PCOS. The varying definitions of PCOS and its heterogeneity confound the interpretation of studies on PCOS. Specific diagnostic criteria have been established based on expert opinion but have not been validated. Several commonly performed laboratory tests are generally unhelpful and the pathophysiology is poorly understood. Treatment options for Ms R, including those that may affect her weight gain, are reviewed and implications for future fertility are discussed.
Clinical Phenotypes of Psychosis in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP)
Authors: Carol A. Tamminga, Elena I. Ivleva, Matcheri S. Keshavan, Godfrey D. Pearlson, Brett A. Clementz, Bradley Witte, David W. Morris, Jeffrey Bishop, Gunvant K. Thaker, John A. Sweeney
Journal: American Journal of Psychiatry (2013)

Objective Developing categorical diagnoses that have biological meaning within the clinical phenotype of psychosis (schizophrenia, schizoaffective disorder, and bipolar I disorder with psychosis) is as important for developing targeted treatments as for nosological goals. The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) was formed to examine a broad array of intermediate phenotypes across psychotic disorders and to test the hypothesis that intermediate phenotype characteristics are homogeneous within phenomenologically derived DSM-IV diagnoses. Method The consortium recruited 933 stable probands with schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder, 1,055 of their first-degree relatives, and 459 healthy comparison subjects for clinical characterization and dense phenotyping. Clinical, psychosocial, and family characteristics were contrasted. Results All proband groups showed lower psychosocial functioning than the relatives or comparison group. On average, schizophrenia probands showed more symptoms and lower psychosocial functioning than probands with psychotic bipolar disorder, but there was considerable overlap in clinical manifestations. The characteristics of schizoaffective disorder were more often similar to schizophrenia than to psychotic bipolar disorder. The rates of lifetime suicide attempts were high across all proband groups, with the highest reported frequencies in the schizoaffective and bipolar groups. Proband family lineages included both families with “pure” psychosis diagnoses and families with mixed schizophrenia-bipolar diagnoses. Conclusions Symptoms, psychosocial functioning, and familial lineage overlap across the three DSM-IV psychosis diagnoses used in B-SNIP. The comingling of psychosis diagnoses within families suggests overlapping genetic determinants across psychoses. These data provide scant evidence for distinct phenotypic clustering around traditional phenomenological diagnoses.
Topical effects of 16,16 dimethyl prostaglandin E2 on gastric acid secretion and mucosal permeability to hydrogen ions in dogs.
Authors: L Y Cheung, S F Lowry, J Perry, K Larson
Journal: Gut (1978)

The effects of luminal instillation of 16,16 dimethyl PGE2 (dmPGE2) on gastric acid secretion and back diffusion of H+ were studied in anaesthetised dogs which were prepared with a segment of the greater curvature of the stomach mounted in a double lumen chamber. This model permitted simultaneous evaluation of two segments of mucosa, one control and the other test, supplied by the same vascular pedicle. Imfusion of histamine (1.0 microgram/kg/min, intravenously) stimulated brisk acid secretion in both chambers. Topical application of 25 microgram dmPGE2 in 20 ml 0.3 M HC1 to the test chamber for 30 minutes prevented acid secretion from the test mucosa during a second histamine infusion. Since the control chamber showed no evidence of inhibition this indicates that dmPGE2 acted directly on the secretory cells, rather than after absorption from the bloodstream. This observation, however, does not exclude a possible local effect on mucosal blood flow. Direct exposure of the gastric mucosa to dmPGE2 increased the rate of back diffusion of H+ because of disruption of the permeability barrier, indicated by increased H+ back diffusion, Na+ efflux, and a reduction in potential difference. However, H+ loss was small compared to the reduction in acid output.
Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus
Authors: Meletios A. Dimopoulos, Efstathios Kastritis, Roger G. Owen, Robert A. Kyle, Ola Landgren, Enrica Morra, Xavier Leleu, Ramón García-Sanz, Nikhil Munshi, Kenneth C. Anderson, Evangelos Terpos, Irene M. Ghobrial, Pierre Morel, David Maloney, Mathias Rummel, Véronique Leblond, Ranjana H. Advani, Morie A. Gertz, Charalampia Kyriakou, Sheeba K. Thomas, Bart Barlogie, Stephanie A. Gregory, Eva Kimby, Giampaolo Merlini, Steven P. Treon
Journal: Blood (2014)
Type 2 Diabetes in the Young: The Evolving Epidemic
Authors: George Alberti, Paul Zimmet, Jonathan Shaw, Zachary Bloomgarden, Francine Kaufman, Martin Silink
Journal: Diabetes Care (2004)

1.The aims of the consensus meeting were to review the epidemiology, pathophysiology, management, and implications of the rising prevalence of type 2 diabetes in young people and to suggest means by which the continuing rise in incidence and prevalence might be prevented.
Legal Disputes over Duties to Disclose Treatment Risks to Patients: A Review of Negligence Claims and Complaints in Australia
Authors: Marie M. Bismark, Andrew J. Gogos, Richard B. Clark, Russell L. Gruen, Atul A. Gawande, David M. Studdert
Journal: PLoS Medicine (2012)

David Studdert and colleagues identified disputes over informed consent among malpractice claims and serious health care complaints in Australia and provide an analysis of disagreements between patients and doctors over whether particular clinical risks should have been disclosed before treatment.
Air Pollution and ST-Segment Depression in Elderly Subjects
Authors: Diane R. Gold, Augusto A. Litonjua, Antonella Zanobetti, Brent A. Coull, Joel Schwartz, Gail MacCallum, Richard L. Verrier, Bruce D. Nearing, Marina J. Canner, Helen Suh, Peter H. Stone
Journal: Environmental Health Perspectives (2005)

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61-88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During postexercise rest, an elevated BC level was associated with -0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression > or = 0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic.