tbuckley/cabot-search huggingface dataset:
Expression of the calcium-sensing receptor on human antral gastrin cells in culture.
Authors: J M Ray, P E Squires, S B Curtis, M R Meloche, A M Buchan
Journal: Journal of Clinical Investigation (1997)

The presence of the extracellular calcium-sensing receptor on human antral gastrin cells was investigated. Reverse transcription PCR using mRNA isolated from gastrin cell- enriched cell cultures identified a product with a sequence identical to part of the human parathyroid-secreting cell calcium-sensing receptor. Immunocytochemistry with an antibody to the extracellular region of the receptor immunostained all gastrin cells (but not mucin or somatostatin cells), and detected appropriate-sized bands in Western blots of whole cell lysates. Increasing extracellular calcium levels from 0.5 to 9 mM stimulated gastrin release in a concentration-dependent manner, with maximal release obtained at 7.2 mM. A known agonist of the calcium receptor, spermine also stimulated gastrin release. Microfluorimetry of identified gastrin cells demonstrated that increasing extracellular calcium resulted in an initial rapid rise in intracellular calcium followed by a plateau level that returned to basal levels immediately after removal of the elevated calcium. The traces were consistent with activation of a receptor-mediated mechanism rather than a concentration-dependent influx of calcium. In conclusion, these data indicate that G cells express the calcium-sensing receptor, and that activation of the receptor may explain the acid rebound phenomenon associated with calcium-containing antacid preparations.
Leukotriene receptor antagonists as potential steroid sparing agents in a patient with serosal eosinophilic gastroenteritis
Authors: M C Urek
Journal: Gut (2006)

Eosinophilic gastroenteritis is a heterogeneous and uncommon disorder characterised by eosinophilic inflammation of the gastrointestinal tissues. The location and depth of infiltration determine its various manifestations and later serve as the basis for its classification as mucosal, muscular, and serosal forms of eosinophilic gastroenteritis. The gold standard for diagnosis is an endoscopic biopsy showing prominent tissue eosinophilia. Gastrointestinal mucosal involvement causes malabsorption, protein losing enteropathy, and diarrhoea. Infiltration of the muscular layer of the bowel wall may cause gastric outlet or small bowel obstruction. Serosal involvement causes exudative ascites rich in eosinophils; this is the least common form and is usually diagnosed by laparoscopic examination and biopsy of the whole intestinal wall. …
Bile acid synthesis by long-term cultured cell line established from human hepatoblastoma.
Authors: Y Amuro, M Tanaka, K Higashino, E Hayashi, T Endo, S Kishimoto, H Nakabayashi, J Sato
Journal: Journal of Clinical Investigation (1982)

Bile acids in the spent medium for the cell culture were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry to determine whether human hepatoblastoma cell line could synthesize bile acids. Cholic, chenodeoxycholic, and lithocolic acids were found in the culture medium, and a portion of chenodeoxycholic acid and all of lithocholic acid were sulfated. Since the cells had been cultured in serum-free medium, it is clear that the bile acids were newly synthesized and sulfated by the cultured cells. Chenodeoxycholic acid was the main bile acid in the medium, suggesting that the cell line might predominantly synthesize chenodeoxycholic acid. On the other hand, the cells had fetal or hepatoma characters such as marked alpha-fetoprotein production. These results suggest that fetal or hepatoma type bile acid metabolism might occur in the cell line, and that the established cell line could be an useful in vitro model for the study of bile acid metabolism in hepatoma.
Patient and general practitioner delays in acute myocardial infarction
Authors: J. M Rawles, N. E Haites
Journal: BMJ (1988)

The longest component of the total delay in coming under coronary care is patient delay, and it has been suggested that public education might be used to make it shorter. The patterns of patient delay were studied in 450 patients with acute myocardial infarction uncomplicated by cardiac arrest out of hospital, of whom 243 had a previous history of ischaemic heart disease. Patient delays had a skewed distribution with a modal delay of up to one hour, a median delay of two hours, and a mean delay of 10 hours. Two thirds of patients had sought help from their general practitioners within four hours of the onset of symptoms. During the first four hours the longer that patients delayed the lower was the subsequent mortality (27%, 18%, and 9% for delays of one hour or less, up to two hours, and up to four hours, respectively), but patients who delayed four to eight hours had the highest mortality of all (38%). Neither the median value nor the pattern of patient delays was altered by a previous history of ischaemic heart disease. There were pronounced differences in doctor delays, depending on the patient9s age, delay time, and ultimate place of treatment, showing that the doctors9 behaviour was influenced before they had seen their patients. Nevertheless, the median total delay for patients aged up to 70 was one hour 35 minutes, and a higher proportion of patients were seen early after infarction than in recent hospital trials of thrombolytic treatment. These findings suggest that the patients9 call for help and the doctors9 response may be at an instinctive level according to the patients9 distress; these patterns of behaviour may be difficult to modify by public education.
Two-generation saccharin bioassays.
Authors: D L Arnold
Journal: Environmental Health Perspectives (1983)

The controversy regarding the safety of saccharin for human consumption started shortly after its discovery over 100 years ago and has yet to subside appreciably. The consumption of saccharin, particularly in North America, began to escalate when the U.S. Food and Drug Administration set new standards of identity which allowed foods containing artificial sweeteners to be promoted as "nonnutritive" or "noncaloric" sweeteners for use by the general public. In 1969, when cyclamates were banned, at least 10 single-generation feeding studies were undertaken with saccharin to more accurately assess the potential toxicological consequences resulting from the anticipated increase in its consumption. None of these studies resulted in any overt regulatory action. Subsequently, the introduction of the two-generation chronic toxicity/carcinogenicity bioassay added a new tool to the toxicologist's arsenal. Three two-generation studies using saccharin have since been conducted. The results from these studies clearly show that when rats were exposed to diets containing 5 or 7.5% sodium saccharin from the time of conception to death, an increased frequency of urinary bladder cancers was found, predominantly in the males. While some study results suggested that impurities in commercial saccharin or the presence of urinary tract calculi may have been responsible for the observed bladder tumors, it now appears that these possibilities are highly unlikely. The mechanism by which saccharin elicited the bladder tumors using the two-generation experiment has not been ascertained.
Effect of Noninvasive Positive-Pressure Ventilation on Survival in Amyotrophic Lateral Sclerosis
Authors: Loutfi Sami Aboussouan
Journal: Annals of Internal Medicine (1997)

Noninvasive positive-pressure ventilation may benefit patients with amyotrophic lateral sclerosis and respiratory insufficiency.To determine 1) whether patients tolerant of noninvasive positive-pressure ventilation have better survival than intolerant patients and 2) whether bulbar symptoms account for intolerance of noninvasive positive-pressure ventilation.Observational cohort study.Tertiary care referral center.39 patients with amyotrophic lateral sclerosis who were treated with noninvasive positive-pressure ventilation.Noninvasive positive-pressure ventilation was started for patients with new orthopnea, new hypercapnia, or both. Patients were divided into two groups: those tolerant of and those intolerant of noninvasive positive-pressure ventilation.The risk for death from onset of respiratory insufficiency was higher for intolerant patients than for tolerant patients (relative risk, 3.1 [95% CI, 1.8 to 9.6]). Moderate or severe bulbar symptoms were more prevalent among intolerant patients than among tolerant patients (67% compared with 33%; P = 0.04).Among patients with amyotrophic lateral sclerosis, those who are tolerant of noninvasive positive-pressure ventilation have better survival than do those who are intolerant. Bulbar symptoms partially account for intolerance of noninvasive positive-pressure ventilation.
Essential inputs for studies of cost-effectiveness analysis in melanoma
Authors: R.L. Morton
Journal: British Journal of Dermatology (2014)

Journal Article Essential inputs for studies of cost‐effectiveness analysis in melanoma Get access R.L. Morton R.L. Morton School of Public Health The University of Sydney Sydney NSW AustraliaHealth Economics Research Centre (HERC) Nuffield Department of Population Health University of Oxford Headington U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 6, 1 December 2014, Pages 1294–1295, https://doi.org/10.1111/bjd.13455 Published: 01 December 2014
The mutation in the mitochondrial aldehyde dehydrogenase (ALDH2) gene responsible for alcohol-induced flushing increases turnover of the enzyme tetramers in a dominant fashion.
Authors: Q Xiao, H Weiner, D W Crabb
Journal: Journal of Clinical Investigation (1996)

Deficiency in mitochondrial aldehyde dehydrogenase (ALDH2), a tetrameric enzyme, results from inheriting one or two ALDH2*2 alleles. This allele encodes a protein subunit with a lysine for glutamate substitution at position 487 and is dominant over the wild-type allele, ALDH2*1. The ALDH2*2-encoded subunit (ALDH2K) reduces the activity of ALDH2 enzyme in cell lines expressing the wild-type subunit (ALDH2E). In addition to this effect on the enzyme activity, we now report that ALDH2*2 heterozygotes had lower levels of ALDH2 immunoreactive protein in autopsy liver samples. The half-lives of ALDH2 protein in HeLa cell lines expressing ALDH2*1, ALDH2*2, or both were determined by the rate of loss of immunoreactive protein after inhibition of protein synthesis with puromycin and by pulse-chase experiments. By either measure, ALDH2E enzyme was very stable, with a half-life of at least 22 h. ALDH2K enzyme had an enzyme half-life of only 14 h. In cells expressing both subunits, most of the subunits assemble as heterotetramers, and these enzymes had a half-life of 13 h. Thus, the effect of ALDH2K on enzyme turnover is dominant. These studies indicate that the ALDH2*2 allele exerts its dominant effect both by interfering with the catalytic activity of the enzyme and by increasing its turnover. This represents the first example of a dominantly acting allele with this effect on a mitochondrial enzyme's turnover.
Predictors of glycemic control in insulin-using adults with type 2 diabetes.
Authors: G A Nichols, T A Hillier, K Javor, J B Brown
Journal: Diabetes Care (2000)

OBJECTIVE: To determine the characteristics that influence glycemic control among insulin-using adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied all 1,333 eligible members of a large not-for-profit health maintenance organization who responded to a 1997 survey. We tested associations among demographic, treatment, and psychometric variables with mean 1997 HbA1c values. The Problem Areas in Diabetes (PAID) instrument was used to assess the emotional effect of living with diabetes, and the Short Form 12 Physical Function Scale was used to assess the effect of physical limitations on daily activities. Based on differences between and within treatment groups, we built models to predict glycemic control for subgroups of subjects who were using insulin alone and those who were using insulin in combination with an oral hypoglycemic agent. RESULTS: Younger age, lower BMI, and increased emotional distress about diabetes (according to the PAID scale) were all significant predictors (P &amp;lt; 0.05) of worse glycemic control. However, except among individuals with an HbA1c level of &amp;gt;8.0 who were receiving combination therapy, only approximately 10% of the variance in glycemic control could be predicted by demographic, treatment, or psychometric characteristics. CONCLUSIONS: Personal characteristics explain little of the variation in glycemic control in insulin-using adults with type 2 diabetes. Possible explanations are that the reduced complexity of control in type 2 diabetes makes the disease less sensitive to personal factors than control in type 1 diabetes, that health-related behavior is less driven by personal and environmental characteristics among older individuals, or that, in populations exposed to aggressive glycemic control with oral hypoglycemic agents and nurse care managers, personal differences become largely irrelevant.
Origin of epicardial ST-T wave potentials in the intact dog.
Authors: M S Spach, R C Barr
Journal: Circulation Research (1976)

Ventricular repolarization was analyzed by measuring epicardial potential distributions in intact dogs with single or multiple ectopic foci and a minimum at the terminal site(s) of excitation. During the latter half of the T wave the distributions became more complex, and two maxima evolved from the initial one at each ectopic site. The measured epicardial potentials were simulated by means of a model of ST-T wave events that is suitable for study of single and multiple ectopic beats with fusion, a a model we call 'SI model.' Intracellular potentials around the ventricles during repolarization were calculated from measured excitation sequences and known action potential shapes. The extracellular potentials around the ventricles were computed from the intracellular ones by a simplified ventricular geometry. The satisfactory agreement between the theoretical and measured extracellular potential distribution shows that the complex changes which occur throughout the ST-T wave are predicted well on the basis of changes in the intracellular potential distributions. In contrast to the well known lability of the T wave from beat, the results show that for any single beat the events of repolarization proceed in an entirely repeatable and deterministic fashion. The results present a way to directly represent cardiac extracellular events during the ST-T wave, a method analogous to the use of isochromes during QRS, and they imply that in the future it will by possible to achieve a more precise quantitative understanding of the events of the ST-T wave than thus far has been possible for QRS.
Prevalence of Congenitally Absent Pedal Pulses
Authors: Donald A. Barnhorst, Hendrick B. Barner
Journal: New England Journal of Medicine (1968)

PALPATION of the pedal pulses is a part of the physical examination for evaluation of the peripheral circulation. To interpret the findings of this examination it is necessary to know the normal occurrence of both the dorsalis pedis and the posterior tibial pulses. Previous studies on the frequency of absent pedal pulses may be criticized on the basis that the sample was numerically small or that the age distribution was inappropriate. We have surveyed 1000 infants and children to establish the prevalence of congenitally absent pedal pulses.MethodOne thousand children between the ages of one and 10, who were . . .
WHO obesity charter seems more like a mantra
Authors: Carrie H Ruxton
Journal: BMJ (2006)

How much will Herceptin really cost? Balancing local and national priorities is not newEditor-Herceptin for early stage breast cancer is a cost effective treatment, and it is right that the NHS should make it available.The challenge of funding new treatments and balancing local and national priorities is one the NHS has faced since its inception. 1 The process the National Institute for Health and Clinical Excellence (NICE) follows for evaluating new medicines is the most rigorous anywhere in the world, and local NHS organisations can have confidence that implementing our recommendations is an effective use of their resources.NICE's independent advisory committees do not rubber stamp decisions.They make them based on an objective and impartial interpretation of the evidence.Those who suggest otherwise should come forward with their evidence for doing so.It is wrong to suggest that a single recommendation from NICE will necessarily cause other services to be reduced and that these decisions are made by clinicians only.Many demands are made on available funds in any hospital at any one time and it is the responsibility of local NHS management, working with their clinical teams, to make the best use of these resources.This difficult job is made easier by NICE guidance and the support tools we offer, such as our commissioning guides and our forthcoming advice on shifting spending from less to more effective treatments.
AB1033 Impact of autoimmune liver disesase on bone mineral density
Authors: H. Kchir, N. Maamouri, N. Belkahla, H. Sahli, B. Mohsni, N. Naija, S. Chouaib, S. Sallemi, N. Ben Mami
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Bone involvement is actually well demonstrated during chronic hepatopathies. Its frequency is not negligible and seems more frequent during auto-immune hepatopathies. <h3>Objectives</h3> To study bone mineral density profile of patients suffering from chronic hepathopathies and to establish characteristics of osteoporotic patients. <h3>Methods</h3> We carried a retrospective study from January 1996 to December 2009 including all cases of auto-immune hepatopathies [auto-immune hepatitis (AIH), primary biliary cirrhosis (PBC), Primary sclerosing cholangitis (PSC), Overlap syndrome PBC-AIH (OS1) and PSC-AIH (OS2)], diagnosed in the department of gastroenterology B in Rabta's Hospital. We retained all patients having a bone densitometry (BD). <h3>Results</h3> During the period of the study, 85 patients were included. Thirty one had a BD: 20 PBC, 2 AIH, 7 OS1, 1 PSC, 1 OS2. BD was normal in 8 cases (25%): 5 PBC and 3 OS1. Osteopenia was reported in 6 cases (19.3%): 4PBC, 1 AIH and 1 OS1. Seventeen patients had osteoporosis (54%): 11 PBC, 1 AIH, 3 OS1, 1 PSC and 1 OS2. The mean T-score was (-3.35 DS) on lumbar spine and (-1.93 DS) on femur. The mean Z score was (-2.1 DS) on lumbar spine and (-0.7 DS) on femur. The mean age of osteoporotic patients was 56,8 years (extreme: 38-76 years). There were 16 women (94%) and one man. Among women, 13 were already postmenopausal (81%). Research of risk factors of osteoporosis revealed a corticotherapy in all cases of OS1 and smoking in 1 case (9% CBP). Biological tests showed transaminase 2-fold above normal values, in 8 cases (47%) with gammaglutamyl transpeptidase ≥5-fold above normal values in 6 patients (35%). The mean rate of bilirubin was 58 mg/l. The immunological tests revealed the presence of anti-mitochondrion-antibodies in 11 cases (9 PBC and 2 OS1), antinuclear-antibodies in 3 cases (2 OS1 and 1 AIH) and anti-smooth-muscle antibodies in 3 cases (2 OS1 and 1 AIH). Associated autoimmune manifestations were observed in 10 cases. A fibrosis degree ≥2 (according to Metavir score) was noted in 10 cases of which 6 were at the stage of cirrhosis at the time of the diagnosis (37%). <h3>Conclusions</h3> In our series, more than half of the patients with auto-immune liver diseases and having had a BD were osteoporotic. Bone loss is generally associated with PBC and is more frequent in postmenopausal women. <h3>Disclosure of Interest</h3> None Declared
A Novel Functional Polymorphism in the<i>Transforming Growth Factor-β2</i>Gene Promoter and Tumor Progression in Breast Cancer
Authors: Julia Beisner, Miriam B. Buck, Peter Fritz, Jürgen Dippon, Matthias Schwab, Hiltrud Brauch, Gerhard Zugmaier, Klaus Pfizenmaier, Cornelius Knabbe
Journal: Cancer Research (2006)

Abstract Transforming growth factor-β (TGF-β), a multifunctional growth factor, plays an important role in breast cancer. There is increasing evidence that enhanced expression of TGF-β promotes breast cancer progression contributing to metastasis and invasiveness of the tumor. We identified a functional polymorphism in the TGFB2 promoter, a 4-bp insertion at position −246 relative to the transcriptional start site (−246ins). Transient transfection experiments showed that the −246ins polymorphism significantly increased TGFB2 promoter activity in breast cancer cells. Electrophoretic mobility shift assays revealed binding of the transcription factor Sp1 to the −246ins allele. Overexpression of Sp1 enhanced promoter activity of the −246ins allele, demonstrating that Sp1 mediates transcriptional activation. Furthermore, the −246ins allele was associated with enhanced TGF-β2 expression in breast cancer tissue (P = 0.0005). To evaluate the role of the polymorphism in breast cancer, frequency of the −246ins allele was determined in breast cancer patients (n = 78) and healthy female controls (n = 143). No significant differences were found. However, the presence of the −246ins allele was associated with lymph node metastasis (P = 0.003). The −246ins allele was a significant predictor for lymph node metastasis independent of estrogen and progesterone receptor status in a multivariate logistic regression analysis (P = 0.0118, odds ratio, 5.18; 95% confidence interval, 1.44-18.62). We provide evidence that the TGFB2 −246ins polymorphism leads to enhanced TGF-β2 expression levels in vivo and might thereby contribute to tumor progression and development of metastases. (Cancer Res 2006; 66(15): 7554-61)
In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. In vivo stability of disulfide-linked immunotoxin conjugates.
Authors: N L Letvin, V S Goldmacher, J Ritz, J M Yetz, S F Schlossman, J M Lambert
Journal: Journal of Clinical Investigation (1986)

The stability in vivo and circulatory clearance of immunotoxins were assessed in rhesus monkeys. The immunotoxins studied were T cell-specific monoclonal anti-T11 antibodies conjugated by disulfide linkage to ribosome-inactivating toxins. Intact immunotoxin was detectable in the circulation of the monkeys following a single intravenous infusion. This was demonstrated by quantitative flow-cytometric analysis, gel-filtration, and sodium dodecyl sulfate-gel electrophoresis. This intact conjugate was shown to be functional in the plasma of the infused animals in an in vitro cytotoxicity assay. However, a number of factors contributed to bring the level of circulating immunotoxin to a less than optimal level. When conjugated to a ribosome-inactivating toxin, the antibody was cleared more rapidly than was the native antibody. Furthermore, following infusion, some breakdown of the conjugate occurred, resulting in the generation of detectable levels of circulating free antibody. The present data indicate the feasibility of using immunotoxins as therapeutic tools in man.