tbuckley/cabot-search huggingface dataset:
Laboratory Aids to Diagnosis and Therapy
Authors: H Sobotka, J J Carr
Journal: Annual Review of Medicine (1955)

Clinical Chemistry is a branch of analytical chemistry devoted to the application of analytical techniques to biological systems on the molecular level as aids to diagnosis, prognosis, and treatment. Its operations may be divided into three parts: (a) isolation of the substance sought from interfering materials, (b) reaction of the substance with a suitable reagent, and (c) meas­ urement of a product of the reaction. In a few instances when no appreciable interferences are encountered (enzymatic determination of urea, determina­ tion of bilirubin) or when the substance can be measured directly (photo­ metric determination of hemoglobin, falling drop technique for serum pro­ tein) either one of the first two steps may not be required. Frequently, the most time-consuming operation in an analytical method consists in the isolation of the compound to be analyzed. This is particularly evident in the procedure commonly employed in the hydrolysis and extrac­ tion of urinary keto-steroids and estrogens, in wet ashing and extraction of biological materials for heavy metal analysis, and in extraction, enzymatic dephosphorylation, chromatographic adsorption, and elution, required for the determination of thiamine. The inconvenience of such procedures, rather than disinterest in the results, hampers the more frequent analysis of the substances in question. As an outstanding illustration, sodium and potassium determinations have but recently become a routine procedure after the de­ velopment of the flame photometer as a practical laboratory instrument. Preliminary isolation is necessary only when interfering substances are expected to be present. Although values obtained with Volhard's chloride method will also include bromide and iodide, only traces of these ions occur normally in biological fluids and may, thus, be ignored. Again, since no in­ terferences are encountered in the diazotization reaction for serum bilirubin, this procedure is performed directly without prior preparation of the sample. The necessary degree of preliminary isolation of the ingredient to be meas­ ured depends upon the specificity of the reagent employed in the second step of the analysis. Thus, since urease acts specifically on urea, this com­ pound may be determined in blood directly. However, because ammonia is the product of urease activity which is usually measured, urea in ammonia­ containing fluids must be determined after preliminary removal of ammonia or by correction for its quantity as found by separate analysis.
Effectiveness of a multi-component intensive smoking cessation programme for COPD outpatients: A randomized controlled trial.
Authors: L.C.A. Christenhusz, M.E. Pieterse, J. van der Palen, E.R. Seydel, P.I. van Spiegel, P.D.L.P.M. van der Valk, F.W.J.M. Smeenk
Journal: European Respiratory Journal (2003)

Background: Chronic Obstructive Pulmonary Disease is a widespread health problem. To improve COPD prognosis the only evidence-based treatment is to quit smoking. The smoking cessation programmes available in the Netherlands are insufficient to help patients with smoking related diseases to quit. Therefore, an intensive smoking cessation programme, SmokeStopTherapy (SST), has been designed for Dutch COPD outpatients. Aim: To investigate whether the intensive SST is more effective in reducing the number of smoking outpatients with COPD compared to usual care , which is defined as the Minimal Intervention Strategy for lung patients (LMIS).Method: Patients willing to quit are randomly allocated to SST or LMIS. The SST consists of small-groups and individual counselling and pharmacological treatment (Nicotine Replacement Therapy and Bupropion). Additionally, patients can recycle in case of a relapse. Preliminary self-reported results are presented below. Results: After three months, self-reported point prevalence abstinence of 45.8% was observed for LMIS subjects (N=24), compared to 73.5% (N=34) for SST subjects ( 2 = 4.583; df =1; p<0.05).Discussion: The intensive SST seems to be significantly more effective than brief usual care intervention (LMIS), despite the low number of patients included in this preliminary analysis. Salivary cotinine-validated outcomes will be available soon.
The distribution of p29 protein in normal human skin
Authors: G.B.E. JEMEC, FENELLA WOJNAROWSKA
Journal: British Journal of Dermatology (1987)

In order to identify specific oestrogen-sensitive structures, normal human skin was examined for the binding of the ER D5 antibody which is associated with p29, a 29 kilodalton protein found in the cytoplasm of normal oestrogen-sensitive cells. Strong and specific staining was seen in the epidermis, with a gradient showing the most intense staining in the granular layer. Similar positive staining was seen in the hair follicles and sebaceous glands. Variable staining was seen in the eccrine glands and vessels. These findings demonstrate p29 to be present in these structures, and hence that oestrogens may exert a specific effect on these tissues.
Religion, psychopathology, and substance use and abuse; a multimeasure, genetic-epidemiologic study
Authors: K S Kendler, C O Gardner, C A Prescott
Journal: American Journal of Psychiatry (1997)

The authors sought to 1) understand the sources of familial resemblance for religiosity, 2) clarify the relationship between religiosity and current psychiatric symptoms, current substance use, lifetime psychiatric disorders, and lifetime substance dependence, and 3) explore the stress-buffering properties of religiosity.Data were obtained by personal interview of 1,902 twins from female-female pairs in the population-based Virginia Twin Registry. Measures included 1) 10 items reflecting a range of religious behavior and beliefs, 2) a scale of institutional conservatism of current religious affiliation, 3) previous history of stressful life events, 4) current psychiatric symptoms and substance use, and 5) lifetime psychiatric disorders and substance dependence. Statistical methods used included factor analyses, Cox and linear regression, and twin modeling.Personal devotion and personal and institutional conservatism were all strongly familial, and model fitting suggested that this familial resemblance was due largely to the effect of environmental factors. None of the dimensions of religiosity was strongly associated with lifetime psychopathology or current symptoms, but low levels of depressive symptoms were related to high levels of personal devotion. By contrast, personal devotion and personal and institutional conservatism were significantly and inversely associated with current levels of drinking and smoking as well as lifetime risk for alcoholism and nicotine dependence. Personal devotion, but not personal or institutional conservatism, buffered the depressogenic effects of stressful life events.The dimensions of religiosity are not strongly related to risk for psychiatric symptoms and disorders. However, religiosity may be one of the more important familial-environmental factors that affect the risk for substance use and dependence. Religious devotion but not conservatism assists in coping with stress.
Increased running speed and pre-race muscle damage as risk factors for exercise-associated muscle cramps in a 56 km ultra-marathon: a prospective cohort study
Authors: Martin P Schwellnus, Siddieq Allie, Wayne Derman, Malcolm Collins
Journal: British Journal of Sports Medicine (2011)

Despite the high prevalence of exercise-associated muscle cramping (EAMC) in endurance runners, the aetiology and risk factors for this condition are not fully understood.The purpose of this prospective cohort study was to identify risk factors associated with the development of EAMC in ultra-distance runners.49 runners participating in a 56 km race completed a validated pre-race questionnaire. Pre-race muscle pain in the calves, hamstrings and quadriceps muscles was recorded (visual analogue scale) and pre-race serum creatine kinase (CK) activity was measured. 20 runners reported EAMC (EAMC group) during or within 6 h after the event, while 29 runners reported no cramping (CON group).EAMC was not associated with age, body mass index, sex, recent and past personal best running times, pre-race muscle pain and pre-race training (duration and frequency). Runners in the EAMC group tended to report on average longer training sessions during the 3 days before the race (EAMC 1.2 (1.1), CON 0.6 (1.0); p=0.077). Significant risk factors for EAMC were a past history of EAMC (EAMC 100%, CON 48%; p<0.001) and a faster running time (min) for the first 28 km split time of the race (EAMC 144 (20), CON 157 (14); p=0.029) despite being matched for recent (<15 weeks before race) personal best times in the 42.2 km race. Pre-race CK activity tended to be higher in the EAMC group (EAMC 89 (80), CON 58 (35); p=0.066).Novel risk factors for EAMC in distance runners are a past history of EAMC, faster running pace at the early stage of a race and possibly pre-race muscle damage.
Childhood socioeconomic factors and perinatal characteristics influence development of rheumatoid arthritis in adulthood
Authors: Christine G Parks, Aimee A D'Aloisio, Lisa A DeRoo, Kirstin Huiber, Lisa G Rider, Frederick W Miller, Dale P Sandler
Journal: Annals of the Rheumatic Diseases (2012)

Rheumatoid arthritis (RA) has been associated with lower socioeconomic status (SES), but the reasons for this are not known.To examine childhood SES measures, SES trajectory and other perinatal factors in relation to RA.The sample included 50 884 women, aged 35-74 (84% non-Hispanic white) enrolled 2004-9 in a US national cohort study. In baseline questionnaires, cases (N=424, 0.8%) reported RA diagnosis after age 16, ever use of disease-modifying antirheumatic drugs or steroids for RA and ≥6 weeks bilateral joint swelling. Childhood SES measures are presented as OR and 95% CI adjusted for age and race/ethnicity. Analyses of perinatal factors also adjusted for childhood SES, and joint effects of childhood and adult SES and smoking exposures were evaluated.Patients with RA reported lower childhood household education (<12 years vs college degree; OR=1.7; 95% CI 1.1 to 2.5), food insecurity (OR=1.5, 95% CI 1.1 to 2.0) and young maternal age (<20 vs 20-34 years; OR=1.7, 95% CI 1.2 to 2.5), with a trend (p<0.0001) for increasing number of adverse factors (OR=3.0; 95% CI 1.3 to 7.0; 4 vs 0 factors) compared with non-cases. Low birth weight (<2500 g) [corrected] and preconception paternal smoking were independently associated with RA. Together, lower childhood SES and adult education (<college degree) were associated with RA (interaction p=0.03), with a joint effect magnitude similar to a history of paternal and adult smoking.RA was associated with low childhood SES sustained into adulthood, with cumulative effects across multiple measures, suggesting the importance of other unmeasured factors linking SES and RA.
Hypotensive effect of clonidine during sodium depletion in the rat.
Authors: D T Pals
Journal: Circulation Research (1975)

Clonidine was nonhypotensive in conscious unrestrained rats maintained on a normal sodium intake. In contradistinction, clonidine caused a dose-related hypotension in conscious unrestrained rats subjected to sodium depletion via furosemide. The plasma renin activity of normal and sodium-depleted rats was reduced after the administration of clonidine (100 mug/kg, iv) by 22.8% and 34.4%, respectively. Intravenous infusion of an angiotensin II antagonist, 1-Sar-8-Ala-angiotensin II, caused a significant reduction of arterial blood pressure in sodium-depleted rats but not in normal rats. Similarly, bilateral nephrectomy reduced arterial blood pressure and completely abolished the hypotensive effect of clonidine in sodium-depleted rats. Subcutaneous administration of chlorisondamine caused a significantly greater reduction of arterial blood pressure in sodium-depleted rats than it did in normal rats. Treatment of normal and sodium-depleted rats with 6-hydroxydopamine reduced the arterial blood pressure of both groups to approximately 85 mm Hg and completely abolished the hypotensive effect of clonidine in the sodium-depleted rats. The data presented in this paper are consistent with the conclusion that clonidine acts at some site in the sympathetic nervous system of sodium-depleted rats to inhibit renal nerve activity with a resultant suppression of renin secretion and a reduction of the angiotensin II-maintained arterial blood pressure. A similar sequence of events occurring in normal rats would not result in hypotension because their arterial blood pressure is not maintained by angiotensin II.
Nasal potential difference in cystic fibrosis patients presenting borderline sweat test
Authors: A Delmarco, U Pradal, G Cabrini, A Bonizzato, G Mastella
Journal: European Respiratory Journal (1997)

The diagnosis of cystic fibrosis (CF) can be difficult if the sweat test and routine deoxyribonucleic acid (DNA) analysis are inconclusive. Under these circumstances, measurement of nasal potential difference (NPD) was proposed as a complementary diagnostic tool, as demonstrated in subjects bearing the G551S or 3849+10KbC--&gt;T mutations. The purpose of the present study was to verify the diagnostic value of this technique in CF patients with a borderline sweat test. NPD was measured in 18 patients with a borderline sweat test, in whom CF diagnosis was based on the presence of one CF gene mutation in each chromosome (CF borderline). These patients were compared both to non-CF controls and CF patients with an abnormal sweat test (CF controls). Basal NPD values of CF borderline patients (mean value -39+/-6 mV, range -29 to -52 mV; n=18) were in the pathological range of CF controls (-39+/-8 mV, range -28 to -57 mV; n=37), and both were statistically different from values obtained in non-CF controls (-15+/-4 mV, range -6 to -23 mV; n=24; p&lt;0.0001). Mutation analysis confirmed a high frequency of the 3849+10KbC--&gt;T mutation in this group of CF borderline patients (positive in 14 out of 18 subjects), whereas other mutations, such as AF508, Q552X, N1303K and R1162X, were also found to be associated with this atypical CF phenotype. These results confirm the presence of pathological values of basal NPD in CF patients with borderline sweat test, and also extend this finding to subjects bearing genotypes other than the G551S and 3849+10KbC--&gt;T mutations. The present findings, therefore, confirm the usefulness of measurement of basal nasal potential difference in all those patients in whom diagnosis of cystic fibrosis can be suspected but the sweat test remains inconclusive.
Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia.
Authors: J Lawler, M Sunday, V Thibert, M Duquette, E L George, H Rayburn, R O Hynes
Journal: Journal of Clinical Investigation (1998)

The thrombospondins are a family of extracellular calcium-binding proteins that modulate cellular phenotype. Thrombospondin-1 (TSP-1) reportedly regulates cellular attachment, proliferation, migration, and differentiation in vitro. To explore its function in vivo, we have disrupted the TSP-1 gene by homologous recombination in the mouse genome. Platelets from these mice are completely deficient in TSP-1 protein; however, thrombin-induced platelet aggregation is not diminished. TSP-1-deficient mice display a mild and variable lordotic curvature of the spine that is apparent from birth. These mice also display an increase in the number of circulating white blood cells, with monocytes and eosinophils having the largest percent increases. The brain, heart, kidney, spleen, stomach, intestines, aorta, and liver of TSP-1-deficient mice showed no major abnormalities. However, consistent with high levels of expression of TSP-1 in lung, we observe abnormalities in the lungs of mice that lack the protein. Although normal at birth, histopathological analysis of lungs from 4-wk-old TSP-1-deficient mice reveals extensive acute and organizing pneumonia, with neutrophils and macrophages. The macrophages stain for hemosiderin, indicating that diffuse alveolar hemorrhage is occurring. At later times, the number of neutrophils decreases and a striking increase in the number of hemosiderin-containing macrophages is observed associated with multiple-lineage epithelial hyperplasia and the deposition of collagen and elastin. A thickening and ruffling of the epithelium of the airways results from increasing cell proliferation in TSP-1-deficient mice. These results indicate that TSP-1 is involved in normal lung homeostasis.
PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation
Authors: Muhammad Zaeem Noman, Giacomo Desantis, Bassam Janji, Meriem Hasmim, Saoussen Karray, Philippe Dessen, Vincenzo Bronte, Salem Chouaib
Journal: The Journal of Experimental Medicine (2014)

Tumor-infiltrating myeloid cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) form an important component of the hypoxic tumor microenvironment. Here, we investigated the influence of hypoxia on immune checkpoint receptors (programmed death [PD]-1 and CTLA-4) and their respective ligands (PD-1 ligand 1 [PD-L1], PD-L2, CD80, and CD86) on MDSCs. We demonstrate that MDSCs at the tumor site show a differential expression of PD-L1 as compared with MDSCs from peripheral lymphoid organ (spleen). Hypoxia caused a rapid, dramatic, and selective up-regulation of PD-L1 on splenic MDSCs in tumor-bearing mice. This was not limited to MDSCs, as hypoxia also significantly increased the expression of PD-L1 on macrophages, dendritic cells, and tumor cells. Furthermore, PD-L1 up-regulation under hypoxia was dependent on hypoxia-inducible factor-1α (HIF-1α) but not HIF-2α. Chromatin immunoprecipitation and luciferase reporter assay revealed direct binding of HIF-1α to a transcriptionally active hypoxia-response element (HRE) in the PD-L1 proximal promoter. Blockade of PD-L1 under hypoxia enhanced MDSC-mediated T cell activation and was accompanied by the down-regulation of MDSCs IL-6 and IL-10. Finally, neutralizing antibodies against IL-10 under hypoxia significantly abrogated the suppressive activity of MDSCs. Simultaneous blockade of PD-L1 along with inhibition of HIF-1α may thus represent a novel approach for cancer immunotherapy.
Apolipoprotein E isoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study.
Authors: J B Meigs, J M Ordovas, L A Cupples, D E Singer, D M Nathan, E J Schaefer, P W Wilson
Journal: Diabetes Care (2000)

OBJECTIVE: Insulin resistance and the apolipoprotein (apo) allele e4 have both been associated with coronary heart disease (CHD). We examined the relationship between insulin resistance and apo(e) polymorphisms among participants in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS: During 1991-1995, subjects underwent a clinical examination and an oral glucose tolerance test with measurement of fasting and 2-h glucose, insulin levels, and fasting lipid levels. We measured insulin resistance using the homeostasis model, in which insulin resistance (HOMA-IR) = fasting insulin x glucose/22.5. Apo(e) isoforms and phenotypes were determined in 1983-1987 using isoelectric focusing of plasma VLDL. Of the 2,120 subjects with complete HOMA-IR and apo(e) data, 204 with type 2 diabetes were excluded. The remainder were classified with features of the insulin resistance syndrome including impaired glucose tolerance (1997 American Diabetes Association criteria), hypertension (criteria from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [6th report]), obesity (BMI &amp;gt;85th percentile), high waist-to-hip ratio (&amp;gt;85th percentile), and high triglyceride and low HDL levels (NCEP-2 criteria). We analyzed data with contingency tables and age- and sex-adjusted logistic regression models. RESULTS: Among the 1,916 subjects, the mean age was 55 (range 28-83 years) and 51% were women. Median HOMA-IR was 6.4 (interquartile range 5.2-8.2), and allele frequencies were 7.8, 79.9, and 12.4% for apo(e) alleles e2, e3, and e4, respectively There were no differences in proportions of apo(e) isoforms or alleles across increasing quintiles of HOMA-IR. A less dramatic increase in proportions occurred with elevated triglycerides associated with increasing HOMA-IR among those with apo(e) isoforms 2/2 and 2/3 compared with the others (P &amp;lt; or = 0.01 for interaction). Otherwise, apo(e) did not substantially modify associations between insulin resistance and features of the insulin resistance syndrome. CONCLUSIONS: There is no association between apo(e) polymorphisms and insulin resistance. These appear to represent 2 completely independent risk factors for CHD.
Dual action of FRC8653, a novel dihydropyridine derivative, on the Ba2+ current recorded from the rabbit basilar artery.
Authors: M Oike, Y Inoue, K Kitamura, H Kuriyama
Journal: Circulation Research (1990)

Actions of FRC8653 on the macroscopic and unitary Ba2+ currents were studied using the rabbit basilar artery. Application of (+/-)-FRC8653 (less than 1 microM) increased the amplitude of the inward current when depolarization pulses more negative than -10 mV were applied but inhibited it when depolarization was more positive than 0 mV (in each case from a holding potential of -80 mV). At a holding potential of -40 mV, (+/-)-FRC8653 (greater than 0.1 nM) consistently inhibited the inward current. (-)-FRC8653 (greater than 1 nM) inhibited the amplitude of the inward current evoked by a depolarizing pulse more positive than -10 mV (the holding potential being -80 mV). At the holding potential of -80 mV, but not at -40 mV, (+)-FRC8653 (1 microM) enhanced the current amplitude evoked by a depolarizing pulse more negative than -10 mV but inhibited the current evoked by a pulse more positive than 0 mV. (+/-)-FRC8653 shifted the voltage-dependent inhibition curves to the left, and the slope of the curve became steeper (test pulse of +10 mV). Two types of single Ca2+ channel currents (12 and 23 pS) were recorded from the basilar artery by the cell-attached patch-clamp method. Opening of the 12-pS channel occurred with a depolarizing pulse (-20 mV) from a holding potential of -80 mV, but not from one of -60 mV. (+)-FRC8653 activated, and (-)-FRC8653 inhibited, the 23-pS channel.(ABSTRACT TRUNCATED AT 250 WORDS)