tbuckley/cabot-search huggingface dataset:
Searching for Evidence of Positive Selection in the Human Genome Using Patterns of Microsatellite Variability
Authors: Bret A. Payseur, Asher D. Cutter, Michael W. Nachman
Journal: Molecular Biology and Evolution (2002)

Both natural selection and nonequilibrium population-level processes can lead to a skew in the frequency distribution of polymorphisms. Population-level processes are expected to affect all loci in a roughly equal fashion, whereas selection will affect only some regions of the genome. We conducted a sliding-window analysis of the frequency distribution of microsatellite polymorphisms across the human genome to identify regions that may be under positive selection. The analysis was based on a published data set of 5,257 mapped microsatellites in individuals of European ancestry. Observed and expected numbers of alleles were compared under a stepwise mutation model (SMM) using analytical formulae. Observed and expected heterozygosities were compared under a SMM using coalescent simulations. The two sets of analyses gave similar results. Approximately one-fourth of all loci showed a significant deficit of heterozygosity, consistent with a recent population expansion. Forty-three windows were identified with extreme skews in the frequency distribution of polymorphisms (in the direction of a deficit of heterozygosity, given the number of alleles). If these extreme windows are tracking selection at linked sites, theory predicts that they should be more common in regions of the genome with less recombination. We tested this prediction by comparing recombination rates in these extreme windows and in other regions of the genome and found that extreme windows had a significantly lower recombination rate than the genomic average. The proportion of extreme windows was significantly higher on the X chromosome than on the autosomes. Moreover, all the windows with extreme skews on the X chromosome were found in two clusters near the centromere; both these clusters exhibit markedly reduced recombination rates. These analyses point to regions of the genome that may recently have been subject to positive selection. These results also suggest that the effects of positive selection may be more pronounced on the X chromosome than on the autosomes in humans.
NMR used to study drugs' toxic effects
Authors: H. Carswell
Journal: JAMA (1982)

Nuclear magnetic resonance (NMR) spectroscopy is fast gaining recognition as a potentially powerful tool for the study of metabolic events in tissue, including those produced by drugs. Researchers at the University of Texas Southwestern Medical School at Dallas have been using NMR to study the nature of the cardiotoxic effects of the anticancer agent doxorubicin hydrochloride (Adriamycin) on rabbit hearts by analyzing the resonance signals emitted by phosphorus 31. Preliminary findings, says biophysicist Ray L. Nunnally, PhD, suggest that in vivo spectra produced by NMR not only identify the early cardiac changes that lead to irreversible damage but also may help pinpoint how doxorubicin exerts its injurious effects at the molecular level. A long-established drug, doxorubicin is used to treat a wide variety of cancers. Careful adherence to guidelines for use of the drug has limited the incidence of cardiotoxicity to less than a few percent of patients. Irreversible damage,
Activation of nuclear factor ?B in hepatitis C virus infection: Implications for pathogenesis and hepatocarcinogenesis
Authors: Dar-In Tai, Sun-Lung Tsai, Young-Mao Chen, Yen-Ling Chuang, Cheng-Yuan Peng, I-Shyan Sheen, Chau-Ting Yeh, Kenneth S. Chang, Shao-Nan Huang, George C. Kuo, Yun-Fan Liaw
Journal: Hepatology (2000)

The hepatitis C virus (HCV) core protein is a multifunctional protein. It may bind to the death domain of tumor necrosis factor receptor 1 (TNFR1) and to the cytoplasmic tail of lymphotoxin-β receptor, implying that it may be involved in the apoptosis and anti-apoptosis signaling pathways. In vitro studies have been inconclusive regarding its ability to inhibit or enhance TNF-α-induced apoptosis. To address this issue, electrophoretic mobility shift assay (EMSA) and immunohistochemical studies were used to show the activation of nuclear factor κB (NF-κB) in HCV-infected liver tissues and in HCV core-transfected cells. The activation of NF-κB was correlated with the apoptosis assays. The results showed that NF-κB activation could be shown in HCV-infected livers and HCV core-transfected cells. The data of EMSA correlated with those of immunohistochemical studies, which revealed a higher frequency of NF-κB nuclear staining in HCV-infected than in normal livers. NF-κB activation conferred resistance to TNF-α-induced apoptosis in HCV core-transfected cells. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate sensitized them to TNF-α-induced apoptosis. These findings suggest that HCV infection may cause anti-apoptosis by activation of NF-κB and implicate a mechanism by which HCV may evade the host’s immune surveillance leading to viral persistence and possibly to hepatocarcinogenesis.
Blood Transfusion in Private Practice
Authors: G. H. Macnab
Journal: BMJ (1936)

giLThe transition froin the second to the final stage of treatment must again be gradual, so that four weeks after the beginning of all treatment the patient is following a regime somewhat as follows: 8 a.m.-Belladonna. 8.30-9.30.a.m.-One egg, and two very thin crisp rashers of bacon.Three pieces of thin crisp toast or three breakfast biscuits, with butter, honey, or red currant jelly.Two cups of milky coffee or tea. 10 a.m.-Alkaline powder. 11a.m.-Milk or milky coffee. 12noon.-Alkalinepowder.I p.m.-4 oz. of boiled or steamed fish.3 oz. of well- mashed milky potato.Milk pudding, junket, baked custard, or stewed apple with cream. 2.30 p.m.-Alkaline powder. 4.30 p.n.-Two cups of tea with milk and sugar.One slice of sponge cake. 5.30 p.m.-Alkaline powder. 7-7.30p.m.-Omelette or minced chicken.Mashed turnips, pur6e of peas, vegetable marrow, or well-mashed milky potato.Sweets as at lunch (1 p.m.). 8.30 p.m.-Alkaline powder. 10p.m.-Hot milk or ovaltine. 10.30 p.m.-Alkaline powder.
Somatomedin activity in synovial fluid from patients with joint diseases.
Authors: C L Coates, R G Burwell, K Lloyd-Jones, A J Swannell, G Walker, C Selby
Journal: Annals of the Rheumatic Diseases (1978)

The somatomedin activity in synovial fluids from 50 patients with a variety of joint diseases has been studied and compared with the activity in each of the patient's own serum and a standard reference serum (SRS). The porcine costal cartilage bioassay of Van den Brande and Du Caju (1974a) has been used with the isotopes 3H-thymidine and 35S-sulphate. Synovial fluids from most patients with post-traumatic and post-operative effusions, osteoarthritis and arthritis associated with psoriasis, Reiter's disease, and ankylosing spondylitis stimulated the synthesis of DNA and proteoglycans in cartilage. Synovial fluids from patients with rheumatoid arthritis either had impaired capacity to stimulate DNA synthesis, or they inhibited it; a similar, but less evident pattern was observed for proteoglycan synthesis. Some synovial fluids from patients with miscellaneous synovitides stimulated, while others inhibited cartilage metabolism. It is concluded that the synovial fluid from patients with rheumatoid arthritis and from some patients with miscellaneous synovitides contained an inhibitor(s) to DNA and possibly proteoglycan synthesis. The sera from nearly all the patients stimulated both DNA and proteoglycan synthesis, but the somatomedin potency ratios for serum in terms of SRS were generally less than 1.0. There was a significant inverse correlation between the serum somatomedin potency ratio and the age of the patient.
Pitfalls of pharmacoepidemiology
Authors: J. A Kaye
Journal: BMJ (2000)

<h3>Objective</h3> London has one of the highest identified prevalence of chemsex (sexualised recreational drug use) among men who have sex with men (MSM) in Europe. We examine MSM’s patterns of chemsex and its association with HIV/STI risk behaviours, STI diagnoses and sexual healthcare-seeking behaviours, including if HIV testing behaviour met UK national guidelines (three monthly if engaging in chemsex). <h3>Methods</h3> Cross-sectional survey data from 2013 (n=905) and 2016 (n=739) were collected using anonymous, self-administered questionnaires from MSM recruited in commercial gay venues in London, UK. Descriptive and multivariable analyses, stratified by self-reported HIV status, were conducted. Adjusted prevalence ratios (aPR) with 95% CIs were calculated. <h3>Results</h3> Comparing the 2013 and 2016 surveys, chemsex prevalence in the past year remained stable, in both HIV-negative/unknown-status MSM (20.9% in 2013 vs 18.7% in 2016, p=0.301) and HIV-positive MSM (41.6% in 2013 vs 41.7% in 2016, p=0.992). Combined 2013–2016 data showed that compared with other MSM, those reporting chemsex were more likely to report HIV/STI risk behaviours, including condomless anal intercourse with serodifferent HIV-status partners (HIV-negative/unknown-status men: aPR 2.36, 95% CI 1.68 to 3.30; HIV-positive men: aPR 4.19, 95% CI 1.85 to 9.50), and STI diagnoses in the past year (HIV-negative/unknown-status men: aPR 2.10, 95% CI 1.64 to 2.69; HIV-positive men: aPR 2.56, 95% CI 1.57 to 4.20). 68.6% of HIV-negative/unknown-status men reporting chemsex attended sexual health clinics and 47.6% had tested for HIV more than once in the past year. <h3>Conclusions</h3> Chemsex in London MSM remained stable but high, particularly among HIV-positive men. Irrespective of HIV status, chemsex was associated with engagement in HIV/STI risk behaviours. Frequency of HIV testing in the past year among HIV-negative/unknown-status men was below national recommendations. Promoting combination prevention strategies, including three monthly HIV/STI testing, access to pre-exposure prophylaxis/antiretroviral treatment and behavioural interventions among MSM reporting chemsex, remains vital to address sexual health inequalities in MSM.
NHS Health Check programme: too early to conclude
Authors: J. N. Newton, A. Davis, J. Waterall, K. A. Fenton
Journal: BMJ (2014)

It would be a shame if the debate about the Inter99 trial was limited to the points raised in the accompanying editorial by Gotzsche and colleagues.1 2 Olsen has already pointed out in his rapid response that the stark message of the editorial’s title is not supported by its content.3 The NHS Health Check Expert Scientific and Clinical Advisory Panel has reviewed the Inter99 trial …
The 2006 California Heat Wave: Impacts on Hospitalizations and Emergency Department Visits
Authors: Kim Knowlton, Miriam Rotkin-Ellman, Galatea King, Helene G. Margolis, Daniel Smith, Gina Solomon, Roger Trent, Paul English
Journal: Environmental Health Perspectives (2008)

BackgroundClimate models project that heat waves will increase in frequency and severity. Despite many studies of mortality from heat waves, few studies have examined morbidity.ObjectivesIn this study we investigated whether any age or race/ethnicity groups experienced increased hospitalizations and emergency department (ED) visits overall or for selected illnesses during the 2006 California heat wave.MethodsWe aggregated county-level hospitalizations and ED visits for all causes and for 10 cause groups into six geographic regions of California. We calculated excess morbidity and rate ratios (RRs) during the heat wave (15 July to 1 August 2006) and compared these data with those of a reference period (8–14 July and 12–22 August 2006).ResultsDuring the heat wave, 16,166 excess ED visits and 1,182 excess hospitalizations occurred statewide. ED visits for heat-related causes increased across the state [RR = 6.30; 95% confidence interval (CI), 5.67–7.01], especially in the Central Coast region, which includes San Francisco. Children (0–4 years of age) and the elderly (≥ 65 years of age) were at greatest risk. ED visits also showed significant increases for acute renal failure, cardiovascular diseases, diabetes, electrolyte imbalance, and nephritis. We observed significantly elevated RRs for hospitalizations for heat-related illnesses (RR = 10.15; 95% CI, 7.79–13.43), acute renal failure, electrolyte imbalance, and nephritis.ConclusionsThe 2006 California heat wave had a substantial effect on morbidity, including regions with relatively modest temperatures. This suggests that population acclimatization and adaptive capacity influenced risk. By better understanding these impacts and population vulnerabilities, local communities can improve heat wave preparedness to cope with a globally warming future.
Preferential expression of alphaEbeta7 integrin (CD103) on CD8+ T cells in the psoriatic epidermis: regulation by interleukins 4 and 12 and transforming growth factor-beta
Authors: Y. Teraki, T. Shiohara
Journal: British Journal of Dermatology (2002)

Summary Background Intraepidermal T lymphocytes are a critical element for sustaining the lesional pathology of psoriasis. Integrin αEβ7 (CD103), a ligand for E‐cadherin, may play a role in the localization of pathogenic T cells within the epidermis of psoriatic lesions. However, little information is available regarding αEβ7 expression on intraepidermal T cells in psoriasis. Objectives To examine αEβ7 expression on intraepidermal T cells in psoriatic lesions and the regulation of αEβ7 expression on T cells in response to cytokines. Methods T‐cell expression of αEβ7 was examined by immunohistochemistry and flow cytometry. In vitro regulation of αEβ7 expression on CD4+ or CD8+ T cells purified from peripheral blood of healthy donors was also examined. Results Immunohistochemical staining revealed expression of αEβ7 on a greater proportion of epidermal T cells than dermal T cells. Nearly 30% of intraepidermal CD4+ T cells were found to express αEβ7 on flow cytometry, whereas more than 80% of intraepidermal CD8+ T cells expressed this integrin. In contrast, few T cells expressed αEβ7 in the peripheral blood of psoriatic patients. The in vitro culture experiment confirmed that αEβ7 was preferentially expressed on CD8+ T cells after stimulation with anti‐CD3 monoclonal antibodies. Addition of transforming growth factor‐β and interleukin‐4 upregulated αEβ7 expression on T cells, whereas interleukin 12 downregulated this. Furthermore, αEβ7 expression on established memory CD8+ T cells was not so reversible as that on CD4+ T cells. Conclusions Preferential and stable expression of αEβ7 on CD8+ T cells may be involved in the lesional pathology of psoriasis.
Campylobacter Enteritis in the United States
Authors: MARTIN J. BLASER
Journal: Annals of Internal Medicine (1983)

During a 15-month study, 8097 fecal specimens submitted to clinical microbiology laboratories at eight hospitals in different parts of the United States were examined. Campylobacter jejuni was isolated from 4.6%, Salmonella from 2.3%, and Shigella from 1.0%. Isolation rates for each pathogen were highest from stool specimens that were watery, bloody, or contained leukocytes. The peak isolation rate for C. jejuni was in persons ages 10 to 29 years; for Salmonella, in children younger than age 10 years; and for Shigella, in children ages 5 to 9 years. The clinical features of the three infections were nearly identical. In contrast, abdominal pain, bloody diarrhea, fever, tenesmus, and abnormal sigmoidsocopic findings were present significantly more often in patients infected with C. jejuni than in a control group of patients with diarrhea. Of patients with leukocytes in their stools and a history of fever, 45.9% were infected with one of the three pathogens. Use of laboratory and clinical findings defined groups with high or low risk of these three infections but could not accurately predict isolation. Fecal cultures had the highest yields when obtained from patients within 7 days from the onset of symptoms.
Getting to grips with gluten
Authors: S N McADAM
Journal: Gut (2000)

Ever since Dicke and coworkers identified gluten as the precipitating agent in coeliac disease (CD),1 2 enormous effort has been invested to identify the elements within gluten that are responsible for eliciting the enteropathy. This has been a frustrating endeavour because of the unusual chemistry and huge complexity of gluten proteins. Gluten consists of the alcohol-water extractable fraction of monomeric gliadins and the alcohol-water unextractable fraction of glutenins cross linked into polymers by intermolecular disulphide bonds. The gliadins can be subdivided on the basis of their amino acid sequences into α/β gliadins, γ gliadins, and ω gliadins, while glutenins can be subdivided into low (LMW) and high (HMW) molecular weight glutenins. Importantly, there are numerous variants of each type of gliadins and glutenins in a single wheat variety. Early feeding studies indicated that both gliadin and glutenin fractions were harmful to coeliac patients.2 3Results with glutenins, however, should be interpreted cautiously as the glutenin fraction also contains subunits with characteristic gliadin sequences but which have odd numbers of cysteine residues that results in the formation of intermolecular disulphide bonds.4 The insolubility of gluten further complicates testing of its toxicity. To bypass this problem, gluten is often fragmented, typically with proteolytic enzymes, prior to testing. Proteolytic fragmentation usually generates a vast array of distinct peptides. From our experience, studies that have obtained results with purified fragments without corroborating results with synthetic analogues should be interpreted with caution. We have often found that a minor peptide constituent can mediate the biological effect of an active fraction rather than the major peptide that is detected by sequencing.

The problem of identifying “toxic” sequences has been further complicated by the lack of reliable and relevant toxicity assays. Assays including culturing of atrophic coeliac mucosa,5culturing of fetal chick or …
Evidence based medicine: new storylines needed
Authors: T. Greenhalgh
Journal: BMJ (2009)

In vitro and in vivo studies, in both animal models and human asthmatics, have implicated IL-4 as an important inflammatory mediator in asthma. In a murine asthma model, we examined the anti-inflammatory activities of soluble IL-4R (sIL-4R). In this model, mice sensitized to OVA by i.p. and intranasal (i.n.) routes are challenged with the allergen by i.n. administration. The OVA challenge elicits an eosinophil infiltration into the lungs, with widespread mucus occlusion of the airways, and results in bronchial hyperreactivity. sIL-4R (0.1–100 μg) was administered by either i.n. or i.p. routes before OVA challenge in OVA-sensitized mice. Both blood and bronchoalveolar lavage fluid levels of sIL-4R were significantly elevated compared with controls by i.n. delivery of 100 μg sIL-4R; i.p. delivery of 100 μg sIL-4R only raised blood levels of sIL-4R. The i.n. administration of 100 μg sIL-4R before allergen challenge significantly reduced late phase pulmonary inflammation, blocking airway eosinophil infiltration, VCAM-1 expression, and mucus hypersecretion. In contrast, i.p. delivery of 100 μg sIL-4R inhibited only the influx of eosinophils into the lungs, but not airway mucus release. Furthermore, sIL-4R treatment by either i.n. or i.p. routes did not reduce airway hyperreactivity in response to methacholine challenge. Thus, elevating airway levels of sIL-4R through the administration of exogenous sIL-4R is effective in blocking the late phase pulmonary inflammation that occurs in this murine allergen-challenge asthma model. These results suggest that sIL-4R may have beneficial anti-inflammatory effects in asthmatic patients.
Multifactorial Uptake of Tc-99m Methylene Diphosphonate in Chronic Renal Failure
Authors: Roger E.R. Taylor
Journal: Clinical Nuclear Medicine (2003)

Soft-tissue calcifications are a frequent complication in patients with chronic renal failure. Numerous underlying factors are thought to favor their formation. A case is presented of a patient who was in end-stage renal failure, secondary to glomerulonephritis. A renal transplant had not been successful. She was on long-term dialysis and had suffered aluminum toxicity (positive desferrioxamine test). She complained of proximal myopathy and bone pain.
Endoscopic Diagnosis and Treatment of an Esophageal Bezoar Resulting from Bulk Laxative Ingestion
Authors: J. Pérez-Piqueras, C. Silva, J. Jaqueti, M. A. Sáez, D. Martinez, J. M. Santa, I. Peralba
Journal: Endoscopy (1994)

See also: Esophageal Bezoar: Report of Five More CasesEndoscopy 1995; 27(04): 342-342DOI: 10.1055/s-2007-1005705 See also: A Case of Esophageal Obstruction after Ingestion of a Granular LaxativeEndoscopy 1995; 27(06): 462-462DOI: 10.1055/s-2007-1005744
Beneficial Effect of Chromium Supplementation on Serum Triglyceride Levels in NIDDM
Authors: Nancy A Lee, Charles A Reasner
Journal: Diabetes Care (1994)

OBJECTIVE To investigate the effect of chromium picolinate supplementation on the lipid profile of the predominantly Hispanic population of non-insulin-dependent diabetes mellitus (NIDDM) patients in San Antonio, Texas. RESEARCH DESIGN AND METHODS A prospective, double-blind, placebo-controlled, crossover study was performed on 14 men and 16 women. Initially, each patient was randomly assigned to receive either chromium picolinate or placebo for 2 months. This initial treatment phase was followed by a 2-month washout period. Subjects were then crossed-over and received the alternate capsule for an additional 2 months. Fasting blood glucose, HbA1c, and serum lipids were compared at the end of each treatment phase. RESULTS Twenty-eight of the originally enrolled 30 patients completed the study. There were no adverse reactions to chromium reported. There were no differences noted between the control and chromium-treated subjects in glucose control, high-density lipoprotein cholesterol levels, or low-density lipoprotein cholesterol levels. Triglyceride (TG) levels were reduced significantly (17.4%; P &amp;lt; 0.05) during the 2 months of chromium supplementation. CONCLUSIONS Ours is the first report of a significant reduction in serum TGs in a group of NIDDM patients treated with chromium. The low cost and excellent safety profile of chromium make it an attractive lipid-lowering agent for this population. Long-term studies are needed to determine if the short-term changes in plasma lipids can be sustained.
Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice.
Authors: A Gilhar, Y Ullmann, T Berkutzki, B Assy, R S Kalish
Journal: Journal of Clinical Investigation (1998)

Alopecia areata is a tissue-restricted autoimmune disease of the hair follicle, which results in hair loss and baldness. It is often psychologically devastating. The role of T lymphocytes in this disorder was investigated with cell transfer experiments. Scalp explants from patients were transplanted to severe combined immunodeficiency (SCID) mice and injected with autologous T lymphocytes isolated from involved scalp. T lymphocytes which had been cultured with hair follicle homogenate along with antigen-presenting cells were capable of inducing the changes of alopecia areata, including hair loss and perifollicular infiltrates of T cells, along with HLA-DR and ICAM-1 expression of the follicular epithelium. Similar changes were not noted in grafts injected with scalp-derived T cells that had not been cultured with follicular homogenate. These data indicate that alopecia areata is mediated by T cells which recognize a follicular autoantigen.