tbuckley/cabot-search huggingface dataset:
NITROGEN METABOLISM OF NORMAL AND SARCOMATOUS FIBROBLASTS IN PURE CULTURES
Authors: Lillian E. Baker, Alexis Carrel
Journal: The Journal of Experimental Medicine (1928)

1. Both normal and sarcomatous fibroblasts of the rat utilize many different fragments of the protein molecule for their growth in vitro. Alpha and beta proteoses have approximately equal growth-promoting power. 2. A mixture of peptones, peptides, and amino acids, containing a negligible quantity of proteose, produces a temporary proliferation of normal fibroblasts, and an unlimited multiplication of sarcomatous fibroblasts, provided these substances are derived from liver which contains products of unknown nature that complete the nutritive effect of the protein degradation products. 3. Amino acids contribute to the nutrition of the cells, but are unable without the addition of peptides or polypeptides to support their life. 4. The proteolytic products are more toxic to normal than to sarcomatous fibroblasts. The hypothesis is suggested that the greater acidity produced by the large glycolysis of the sarcomatous cells may account for this difference through altering the speed of action of protein synthetizing enzymes.
Gene Expression–Based Model Using Formalin-Fixed Paraffin-Embedded Biopsies Predicts Overall Survival in Advanced-Stage Classical Hodgkin Lymphoma
Authors: David W. Scott, Fong Chun Chan, Fangxin Hong, Sanja Rogic, King L. Tan, Barbara Meissner, Susana Ben-Neriah, Merrill Boyle, Robert Kridel, Adele Telenius, Bruce W. Woolcock, Pedro Farinha, Richard I. Fisher, Lisa M. Rimsza, Nancy L. Bartlett, Bruce D. Cheson, Lois E. Shepherd, Ranjana H. Advani, Joseph M. Connors, Brad S. Kahl, Leo I. Gordon, Sandra J. Horning, Christian Steidl, Randy D. Gascoyne
Journal: Journal of Clinical Oncology (2012)

Our aim was to reliably identify patients with advanced-stage classical Hodgkin lymphoma (cHL) at increased risk of death by developing a robust predictor of overall survival (OS) using gene expression measured in routinely available formalin-fixed paraffin-embedded tissue (FFPET).Expression levels of 259 genes, including those previously reported to be associated with outcome in cHL, were determined by digital expression profiling of pretreatment FFPET biopsies from 290 patients enrolled onto the E2496 Intergroup trial comparing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and Stanford V regimens in locally extensive and advanced-stage cHL. A model for OS separating patients into low- and high-risk groups was produced using penalized Cox regression. The model was tested in an independent cohort of 78 patients enriched for treatment failure but otherwise similar to patients in a population-based registry of patients treated with ABVD. Weighted analysis methods generated unbiased estimates of predictor performance in the population-based registry.A 23-gene outcome predictor was generated. The model identified a population at increased risk of death in the validation cohort. There was a 29% absolute difference in 5-year OS between the high- and low-risk groups (63% v 92%, respectively; log-rank P < .001; hazard ratio, 6.7; 95% CI, 2.6 to 17.4). The predictor was superior to the International Prognostic Score and CD68 immunohistochemistry in multivariate analyses.A gene expression-based predictor, developed in and applicable to routinely available FFPET biopsies, identifies patients with advanced-stage cHL at increased risk of death when treated with standard-intensity up-front regimens.
Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.
Authors: K D Setchell, M Schwarz, N C O'Connell, E G Lund, D L Davis, R Lathe, H R Thompson, R Weslie Tyson, R J Sokol, D W Russell
Journal: Journal of Clinical Investigation (1998)

We describe a metabolic defect in bile acid synthesis involving a deficiency in 7alpha-hydroxylation due to a mutation in the gene for the microsomal oxysterol 7alpha-hydroxylase enzyme, active in the acidic pathway for bile acid synthesis. The defect, identified in a 10-wk-old boy presenting with severe cholestasis, cirrhosis, and liver synthetic failure, was established by fast atom bombardment ionization-mass spectrometry, which revealed elevated urinary bile acid excretion, a mass spectrum with intense ions at m/z 453 and m/z 510 corresponding to sulfate and glycosulfate conjugates of unsaturated monohydroxy-cholenoic acids, and an absence of primary bile acids. Gas chromatography-mass spectrometric analysis confirmed the major products of hepatic synthesis to be 3beta-hydroxy-5-cholenoic and 3beta-hydroxy-5-cholestenoic acids, which accounted for 96% of the total serum bile acids. Levels of 27-hydroxycholesterol were > 4,500 times normal. The biochemical findings were consistent with a deficiency in 7alpha-hydroxylation, leading to the accumulation of hepatotoxic unsaturated monohydroxy bile acids. Hepatic microsomal oxysterol 7alpha-hydroxylase activity was undetectable in the patient. Gene analysis revealed a cytosine to thymidine transition mutation in exon 5 that converts an arginine codon at position 388 to a stop codon. The truncated protein was inactive when expressed in 293 cells. These findings indicate the quantitative importance of the acidic pathway in early life in humans and define a further inborn error in bile acid synthesis as a metabolic cause of severe cholestatic liver disease.
In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.
Authors: T Yamada, M Horiuchi, R Morishita, L Zhang, R E Pratt, V J Dzau
Journal: Journal of Clinical Investigation (1995)

DBA/2J mouse contains two renin gene loci (Ren1d and Ren2d). Ren2d but not Ren1d is expressed in submandibular gland (SMG) while both are expressed in the kidney. Based on vitro studies, we have postulated that a negative regulatory element (NRE) in the renin gene promoter is involved in its tissue-specific expression. In this study, we examined the molecular mechanism at the in vivo level using direct gene transfer. Fragments of the Ren1d or Ren2d promoter were fused to a chloramphenicol acetyltransferase (CAT) gene expression vector. These constructs complexed in fusogenic liposomes were injected directly into the mouse SMG or intraarterially into the mouse kidney via the renal artery. The vector containing the CAT exhibited readily detectable in vivo expressions in both SMG and kidney. In the SMG, Ren1d fragment containing the NRE abolished CAT expression while deletion of the NRE restored CAT expression. The homologous fragment from the Ren2d promoter did not inhibit CAT expression while deletion of the 150-bp insertion resulted in the inhibition. Cotransfection of Ren1d construct with Ren1d-NRE oligonucleotides as transcriptional factor decoy restored CAT expression. Contrary to the SMG, transfection with Ren1d fragment-CAT construct or Ren2d fragment-CAT construct into the kidney resulted in similar levels of CAT expression. Interestingly, human c-myc NRE oligonucleotides which share homology with Ren1d-NRE competed effectively with these oligonucleotides for the regulation of Ren1d gene expression in vivo. This NRE sequence is also homologous to silencer elements found in multiple mammalian genes, suggesting the presence of a family of NRE/NRE binding proteins regulating expression of diverse genes.
Preventing falls in elderly people
Authors: Lesley Gillespie
Journal: BMJ (2004)

Motor skills learning is classically associated with brain regions including cerebral and cerebellar cortices and basal ganglia nuclei. Less is known about the role of the hippocampus in the acquisition and storage of motor skills. Here we show that mice receiving a long-term training in the accelerating rotarod display marked hippocampal transcriptional changes and reduced pyramidal neurons activity in the CA1 region when compared with naïve mice. Then, we use mice in which neural ensembles are permanently labeled in an <i>Egr1</i> activity-dependent fashion. Using these mice, we identify a subpopulation of <i>Egr1</i>-expressing pyramidal neurons in CA1 activated in short- and long-term trained mice in the rotarod task. When <i>Egr1</i> is downregulated in the CA1 or these neuronal ensembles are depleted, motor learning is improved whereas their chemogenetic stimulation impairs motor learning performance. Thus, <i>Egr1</i> organizes specific CA1 neuronal ensembles during the accelerating rotarod task that limit motor learning. These evidences highlight the role of the hippocampus in the control of this type of learning and we provide a possible underlying mechanism. <b>Significance statement:</b> It is a major topic in neurosciences the deciphering of the specific circuits underlying memory systems during the encoding of new information. However, the potential role of the hippocampus in the control of motor learning and the underlying mechanisms has been poorly addressed. In the present work we show how the hippocampus responds to motor learning and how the <i>Egr1</i> molecule is one of the major responsible for such phenomenon controlling the rate of motor coordination performances.
Breath sounds in the clinical assessment of airflow obstruction.
Authors: A B Bohadana, R Peslin, H Uffholtz
Journal: Thorax (1978)

In a group of 34 inpatients showing varying degrees of airflow obstruction we studied the relationship between breath sound intensity (BSI) and abnormalities of lung function. The BSI was evaluated by chest auscultation to provide a score, in a manner similar to that described by Pardee et al. (1976), and was found to correlate closely with indices of airflow obstruction of their logarithms such as specific conductance (r = 0.759), maximal expiratory flow at 50% of vital capacity (r = 0.790), forced expiratory volume in one second (r = 0.768), and forced expiratory volume to vital capacity ratio (r = 0.860). Correlations with lung volumes, although statistically significant, were weaker. Multiple correlation studies showed that BSI score correlated independently with indices of both airflow obstruction and lung distension. In our experience, BSI score can be useful not only in the detection but also the quantification of airflow obstruction, although its predictive power is impaired in subjects with associated restrictive disorders. It can also fail to detect mild, pure airflow obstruction.
Qualitative and quantitative expression of VHI associated cross reactive idiotopes within IgM rheumatoid factor from patients with early synovitis.
Authors: F Shokri, R A Mageed, E Tunn, P A Bacon, R Jefferis
Journal: Annals of the Rheumatic Diseases (1990)

Monoclonal rheumatoid factors (RFs) of the major Wa cross reactive idiotype group have been shown to express exclusively VKIII subgroup light chains and VHI subgroup heavy chains. A VKIII associated cross reactive idiotope (CRI) (17-109), however, was shown not to be exclusively expressed on IgM paraproteins having rheumatoid factor activity or to be present at increased levels in the sera of patients with rheumatoid arthritis (RA). Three VHI associated CRIs have been defined with monoclonal antibodies and quantitative studies of their representation are reported, together with VKIII, in IgM and IgM RF isolated from the sera of patients with early synovitis, some of whom progressed to classical RA. The results show (a) the probed CRIs were expressed predominantly on IgM RF rather than on non-RF IgM; (b) 5-10% of IgM RFs from patients with classical RA expressed the CRIs, but this represented a lower proportion of IgM RFs than observed for normal individuals or patients with self limiting synovitis; (c) VKIII light chains were highly associated with IgM RFs rather than non-RF IgM (75% and 25% respectively). It is suggested that the CRIs probed are markers for germline gene encoded antibodies or sequences resulting from minimal mutation of germline genes. The lowered proportion of RFs expressing CRIs in RA may therefore be evidence of polyclonal activation or specific antigenic stimulation, or both, resulting in maturation of the RF response with recruitment of further VH genes or extensive mutation of germline genes. These studies show that monoclonal RFs are relevant models of RF produced in RA and that the repertoire of RF autoantibodies may be encompassed within a small number of CRI expressing families.
Identification of 9 serum microRNAs as potential noninvasive biomarkers of human astrocytoma
Authors: Feng Zhi, Naiyuan Shao, Rong Wang, Danni Deng, Lian Xue, Qiang Wang, Yi Zhang, Yimin Shi, Xiwei Xia, Suinuan Wang, Qing Lan, Yilin Yang
Journal: Neuro-Oncology (2014)

BackgroundCirculating microRNAs (miRNAs) are emerging as promising biomarkers for human cancer. In the current study, we investigated the potential use of serum miRNAs as biomarkers for diagnosis and prognosis in a cohort of Chinese astrocytoma patients.
Homocysteinemia Is Not Changed by 3-Day Insulin-Induced Normoglycemia in Type 2 Diabetic Subjects
Authors: Marie-Christine Beauvieux, Vincent Rigalleau, Caroline Perlemoine, Laurence Baillet, Henri Gin
Journal: Diabetes Care (2003)

Diabetic patients have a two- to sixfold increase in the prevalence of cardiovascular diseases (CVDs) (1). Homocysteinemia is an independent risk factor for CVD (2). Genetic, age- and sex-related, nutritional, and hormonal factors leading to the abnormal regulation of homocysteinemia in diabetes play a role in CVD (3). The relation between homocysteinemia and cardiovascular morbidity remains unclear (4). Type 2 diabetes is the result of insulin resistance paired with a progressive loss of insulin secretion, and the resulting chronic hyperglycemia is associated with long-term CVD. In type 2 diabetes, a 3-day insulin-induced strict normoglycemia improves 1 ) postprandial carbohydrate oxidation evaluated by indirect calorimetry (5) and 2 ) parameters of erythrocytic lipoperoxidation, such as malondialdehyde and vitamin E (6). Few studies …
Thymus-like activities of sulphur derivatives on T-cell differentiation.
Authors: G Renoux, M Renoux
Journal: The Journal of Experimental Medicine (1977)

Levamisole and sodium diethyldithiocarbamate can induce in vivo thymocyte differentiation from precursor spleen cells of nu/nu mice and evoke indirect plaque-forming cells in nude mice immunized with sheep red cells. These sulphur drugs induce in thymusless mice the production of a serum factor which transfer in vivo immune enhancement and in vitro thymocyte differentiation. In vivo treatment with sulphur derivative can substitute for an alleged thymice hormone.
Tubuloglomerular Feedback and Single Nephron Function after Converting Enzyme Inhibition in the Rat
Authors: David W. Ploth, James Rudulph, Ronald Lagrange, L. Gabriel Navar
Journal: Journal of Clinical Investigation (1979)

Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during renin-angiotensin blockade with the converting enzyme inhibitor (CEI) SQ 20881 (E. R. Squibb & Sons, Princeton, N. Y.) (3 mg/kg, per h). Converting enzyme inhibition was documented by complete blockade of vascular responses to infusions of angiotensin I (600 ng/kg). Control plasma renin activity was 12.5±2.7 ng angiotensin I/ml per h (mean±SEM) and increased sevenfold with CEI (n = 7). There were parallel increases in glomerular filtration rate from 1.08±0.05 to 1.26±0.05 ml/min and renal blood flow from 6.7±0.4 to 7.5±0.5 ml/min. During CEI infusion absolute and fractional sodium excretion were increased 10-fold. Proximal tubule and peritubular capillary pressures were unchanged. Single nephron glomerular filtration rate (SNGFR) was measured from both proximal and distal tubule collections; SNGFR based only on distal collections was significantly increased by CEI. A significant difference was observed between SNGFR values measured from proximal and distal tubule sites (6.0±1.6 nl/min) and this difference remained unchanged after CEI administration. Slight decreases in fractional absorption were suggested at micropuncture sites beyond the late proximal tubule, whereas early distal tubule flow rate was augmented by CEI. Tubuloglomerular feedback activity was assessed by measuring changes in proximal tubule stop-flow pressure (SFP) or SNGFR in response to alterations in orthograde microperfusion rate from late proximal tubule sites. During control periods, SFP was decreased 11.2±0.4 mm Hg when the perfusion rate was increased to 40 nl/min; during infusion of CEI, the same increase in perfusion rate resulted in a SFP decrement of 6.7±0.5 mm Hg (P<.001). When late proximal tubule perfusion rate was increased from 0 to 30 nl/min, SNGFR was decreased by 15.0±1.2 nl/min during control conditions, and by 11.3±1.3 nl/min during CEI infusion. Attenuation of feedback responsiveness during CEI was also observed at lower perfusion rates with both techniques. These results indicate that blockade of the renin-angiotensin system with CEI reduces the activity of the tubuloglomerular feedback mechanism which may mediate the observed renal vasodilation.
Increased Frequency of Adenocarcinoma of the Uterine Cervix in Young Women in Los Angeles County&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R K Peters, A Chao, T M Mack, D Thomas, L Bernstein, B E Henderson
Journal: JNCI Journal of the National Cancer Institute (1986)

By hypothesizing that oral contraceptives (OC's) might have a carcinogenic effect on glandular cells of the cervix if given during periods of active metaplasia (e.g., postmenarchal adolescence), an increasing rate of cervical adenocarcinoma was predicted in young women who had been teenagers when OC's were introduced roughly 20 years ago. Secular trends for cervical carcinomas in non-Hispanic whites were examined by age, histologic type, and social class by using data from the Los Angeles County population-based tumor registry. Between 1972 and 1982, the frequency of invasive cervical adenocarcinoma in women under 35 years of age increased from about 2 to about 5 annually, amounting to an average rate of change of 8% per year (P less than .01). There was essentially no trend for women over 35 years old; the frequency of other invasive carcinomas (and of squamous carcinoma in situ) decreased at average rates of about 3% per year in women under 35 years of age and decreased more rapidly in older women. The increase in adenocarcinoma, unlike risk from cervical cancer generally, was most striking among young women residing in middle-to-upper income neighborhoods, who were the first to use OC's; in this subgroup the average rate of increase was 16% per year (P less than .05). These findings are compatible with our hypothesis and merit further study.
Chronic Venous Insufficiency and Varicose Veins
Authors: Seshadri Raju, Peter Neglén
Journal: New England Journal of Medicine (2009)

A 52-year-old receptionist presents with an ulcer on her ankle of 1 year's duration. Narcotic analgesics once or twice a day and leg elevation reduce the pain. She has not had diabetes and does not smoke. Physical examination reveals an ulcer above the medial malleolus, with a clean bed of granulation and surrounded by hyperpigmented skin. Pedal pulses are easily palpable. How should she be evaluated and treated?
DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori–specific immune tolerance, and asthma protection
Authors: Mathias Oertli, Malin Sundquist, Iris Hitzler, Daniela B. Engler, Isabelle C. Arnold, Sebastian Reuter, Joachim Maxeiner, Malin Hansson, Christian Taube, Marianne Quiding-Järbrink, Anne Müller
Journal: Journal of Clinical Investigation (2012)

Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori–specific tolerance. DC depletion resulted in improved control of the infection but also aggravated T cell–driven immunopathology. Consistent with the mouse data, DCs infiltrating the gastric mucosa of human H. pylori carriers exhibited a semimature DC-SIGN+HLA–DRhiCD80loCD86lo phenotype. Mechanistically, the tolerogenic activity of H. pylori–experienced DCs was shown to require IL-18 in vitro and in vivo; DC-derived IL-18 acted directly on T cells to drive their conversion to Tregs. CD4+CD25+ Tregs from infected wild-type mice but not Il18–/– or Il18r1–/– mice prevented airway inflammation and hyperresponsiveness in an experimental model of asthma. Taken together, our results indicate that tolerogenic reprogramming of DCs ensures the persistence of H. pylori and protects against allergic asthma in a process that requires IL-18.
Cardiac adaptation to exercise in adolescent athletes of African ethnicity: an emergent elite athletic population
Authors: Nabeel Sheikh, Michael Papadakis, Francois Carre, Gaelle Kervio, Vasilis F Panoulas, Saqib Ghani, Abbas Zaidi, Sabiha Gati, John Rawlins, Mathew G Wilson, Sanjay Sharma
Journal: British Journal of Sports Medicine (2013)

Background/aims Adult black athletes (BA) exhibit left ventricular hypertrophy (LVH) on echocardiography and marked ECG repolarisation changes resembling those observed in hypertrophic cardiomyopathy (HCM). Limited data are available for adolescent BA, the group most vulnerable to exercise-related sudden cardiac death. Methods Between 1996 and 2011, 245 male and 84 female adolescent BA from a wide variety of sporting disciplines underwent cardiac evaluation including ECG and echocardiography. Athletes exhibiting T-wave inversions and/or echocardiographic LVH were investigated further for quiescent cardiomyopathies. Results were compared with 903 adolescent white athletes (WA) and 134 adolescent sedentary black controls (BC). Results LVH on echocardiography was present in 7% of BA compared to only 0.6% of WA and none of the BC. In the very young (&lt;16 years), 5.5% of BA, but none of the WA, demonstrated LVH. Within the BA group, LVH was more prevalent in men compared to women (9% vs 1.2%, p=0.012). T-wave inversions were present in 22.8% BA, 4.5% WA and 13.4% BC. T-wave inversions in BA occurred with similar frequency in men and women and were predominantly confined to leads V1–V4. T-wave inversions in the lateral leads, commonly associated with cardiomyopathies, were present in 2.4% of BA. On a further evaluation and mean follow-up of 8.3 years, none of the athletes exhibited HCM. Conclusions Athletic training has a pronounced effect on adolescent BA. Black athletes as young as 14 years of age may exhibit left ventricular wall thicknesses of 15 mm and marked repolarisation changes resembling HCM. Male and female BA demonstrate a high prevalence of T-wave inversions.