tbuckley/cabot-search huggingface dataset:
Renal potassium wasting in renal tubular acidosis (RTA)
Authors: Anthony Sebastian, Elisabeth McSherry, R. Curtis Morris
Journal: Journal of Clinical Investigation (1971)

IN TWO PATIENTS WITH CLASSIC RENAL TUBULAR ACIDOSIS (RTA) AND IN TWO PATIENTS WITH RTA ASSOCIATED WITH THE FANCONI SYNDROME, RENAL POTASSIUM WASTING PERSISTED DESPITE SUSTAINED CORRECTION OF ACIDOSIS: (a) during moderate degrees of hypokalemia, daily urinary excretion of potassium exceeded 80 mEq in each patient; (b) during more severe degrees of hypokalemia, daily urinary excretion of potassium exceeded 40 mEq in two patients and 100 mEq in another. These urinary excretion rates of potassium are more than twice those observed in potassium-depleted normal subjects with even minimal degrees of hypokalemia. The persistence of renal potassium wasting may have resulted in part from hyperaldosteronism, since urinary aldosterone was frankly increased in two patients and was probably abnormally high in the others relative to the degree of their potassium depletion. The hyperaldosteronism persisted despite sustained correction of acidosis, a normal sodium intake, and no reduction in measured plasma volume, and was not associated with hypertension; its cause was not defined. In the two patients with classic RTA, neither renal potassium wasting nor hyperaldosteronism could be explained as a consequence of a gradient restriction on renal H(+) - Na(+) exchange because the urinary pH remained greater than, or approximately equal to, the normal arterial pH or considerably greater than the minimal urinary pH attained during acidosis. The findings provide no support for the traditional view that renal potassium wasting in either classic RTA or RTA associated with the Fanconi syndrome is predictably corrected solely by sustained correction of acidosis with alkali therapy.
Physical activity and incidence of non-insulin-dependent diabetes mellitus in women
Authors: J.E. Manson, M.J. Stampfer, G.A. Colditz, W.C. Willett, B. Rosner, C.H. Hennekens, F.E. Speizer, E.B. Rimm, A.S. Krolewski
Journal: The Lancet (1991)
When is an oral food challenge positive?
Authors: B. Niggemann
Journal: Allergy (2009)

Abstract Oral food challenges still remain the gold standard in the diagnosis of food related symptoms and are performed to obtain a clear ‘yes or no’ response. However, this is often difficult to achieve, and so proposals may be appropriate for criteria on when to stop oral food challenges. In daily practice it makes sense to challenge until clear objective symptoms occur without harming the patient. Clinical symptoms should be objective and/or: (a) severe or (b) reproducible or (c) persisting. A sensitive parameter for a beginning clinical reaction is a general change of mood. The sooner symptoms appear, the more likely they are to represent a ‘true’ positive reaction and the more organ systems are involved the easier it is to assess an oral food challenge as positive. In the case of subjective symptoms, the number of placebo doses should be increased. In unclear situations, the observation time until the next dose should be prolonged or the same dose repeated. Transient objective clinical symptoms usually end up in a positive challenge result. There are a number of causes for false positive and false negative challenge results, which should be considered. The aim of all oral challenge testing should be to hold the balance between two conflicting aspects: on the one hand the need to achieve clear and justified results from oral food challenges in order to avoid unnecessary diets, and on the other hand to protect patients from any harm caused by high doses of a potentially dangerous food.
Evidence That γδ versus αβ T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling
Authors: Joonsoo Kang, Ariane Volkmann, David H. Raulet
Journal: The Journal of Experimental Medicine (2001)

Two types of T cells, αβ and γδ, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of αβ lineage T cells requires the surrogate α chain (pTα), which associates with the T cell receptor (TCR) β chain to form the pre-TCR. γδ lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR γ and δ genes. It has been proposed that the quality of signals transmitted by the pre-TCR and γδ TCR are distinct and that these “instructive” signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25+CD44+c-kit+CD3−CD4−CD8− thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into γδ versus αβ lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7Rneg-lo pro-T cells generated a 13-fold higher ratio of αβ lineage to γδ lineage cells than did IL-7R+ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R+ pro-T cells to develop into TCR-γδ T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-γ gene rearrangement/expression in IL-7R+ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals.
Decrease in Postprandial Insulin and Glucose Concentrations by Guar and Pectin
Authors: DAVID J. A. JENKINS
Journal: Annals of Internal Medicine (1977)

Postprandial glycaemia and rise in serum insulin after carbohydrate-containing meals were reduced by the addition of guar flour or pectin, or both. After a liquid test meal (four subjects) the 30-min blood glucose was reduced from 6.33 ± 0.19 mmol/litre (114 ± mg/dl), mean ± SEM, in the control subjects to 4.77 ± 0.17 mmol/litre (86 ± 3 mg/dl) by addition of guar gum (P < 0.05). The mean insulin level was also significantly lower at 15 min. A breakfast test meal (bread, butter, marmalade, and tea) resulted in a mean 15-min blood glucose of 6.18 ± 0.21 mmol/litre (111 ± 4 mg/dl) in eight subjects; 10 g of pectin added to the marmalade reduced this level to 5.64 ± 0.17 mmol/litre (102 ± 3 mg/dl) (P < 0.01). The insulin levels were significantly lower at 15, 30, and 45 min. A similar meal in which guar was added to the bread and pectin to the marmalade resulted in significant reductions of blood glucose at 15 min (P < 0.002) and 30 min (P < 0.01). The insulin values were also significantly lower throughout the first 90 min of the test. This action of unavailable carbohydrate may prove useful in the dietary control of diabetes.
Cryptococcosis in the Acquired Immunodeficiency Syndrome
Authors: JOSEPH A. KOVACS
Journal: Annals of Internal Medicine (1985)

The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7. Meningitis was the commonest clinical feature (18 patients). Blood cultures and serum cryptococcal antigen were frequently positive. In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive. Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy. Standard courses of amphotericin B alone or combined with flucytosine were ineffective. Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.
Role of NHERF-1 in Regulation of the Activity of Na-K ATPase and Sodium-Phosphate Co-transport in Epithelial Cells
Authors: Eleanor DeLand Lederer, Syed Jalal Khundmiri, Edward J. Weinman
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Parathyroid hormone (PTH), acting at least in part through a cAMP signaling pathway, regulates three important transporters in the renal proximal convoluted tubule, namely Na-H exchanger 3, Na-K ATPase, and type IIa sodium phosphate cotransporter (NaPi IIa). The regulation of Na-H exchanger 3 by protein kinase A requires a protein co-factor from the sodium-hydrogen exchanger regulatory factor (NHERF) family of proteins (NHERF-1 and NHERF-2). However, the role of NHERF in PTH regulation of Na-K ATPase and NaPi IIa has not been explored. For studying the role of NHERF-1 on PTH regulation of these transporters, wild-type mNHERF-1 (1-355) or mNHERF-1 (1-325) lacking the ezrin-binding domain were expressed in proximal tubule-derived opossum kidney cells. PTH inhibited Na-K ATPase activity in cells expressing wild-type NHERF-1 associated with increased serine phosphorylation of the α subunit of the transporter. By contrast, in cells expressing mNHERF (1-325), the phosphorylation of the α subunit of Na-K ATPase was blunted and the activity of the transporter was stimulated in response to PTH. Basal sodium-dependent phosphate transport was lower in cells expressing mNHERF-1 (1-325) as compared with cells expressing mNHERF-1 (1-355). Nonetheless, there were no differences in PTH-associated inhibition of the activity or the decrease in membrane expression of the NaPi IIa in any of the cell lines. These experiments document for the first time an association between NHERF-1 and PTH regulation of Na-K ATPase in epithelial cells. These experiments also suggest that the mechanism for retrieval of NaPi IIa transporters from the apical membrane in response to cAMP does not require NHERF. E-mail: e.lederer@louisville.edu
Familial aggregation of undifferentiated spondyloarthropathy associated with HLA-B7.
Authors: B L Kidd, P J Wilson, P R Evans, M I Cawley
Journal: Annals of the Rheumatic Diseases (1995)

To report multiple cases of recurrent seronegative arthropathy, enthesopathy, or both, occurring in a single family in the absence of the HLA-B27 tissue type, coexistent psoriasis or inflammatory bowel disease.Three generations of one family together with their general practitioners completed a standard questionnaire. All subjects with a positive questionnaire and two randomly chosen subjects with negative questionnaires were then examined by a single observer. HLA tissue typing and standard sacroiliac radiographs were performed.Seven of 12 family members with a positive questionnaire had early onset oligo- or polyarthritis, enthesitis, or both, and fulfilled established criteria for spondyloarthropathy, although none had radiological evidence of sacroiliitis. The mean age at first symptom in this group was 22 years with only one individual having the first symptom over the age of 30 years. All subjects were rheumatoid factor negative. Histocompatibility studies showed a strong association with the HLA-B7 antigen.The observations provide further support for the existence of 'undifferentiated' spondyloarthropathy and suggest that this can be associated with genetic factors other than HLA-B27.
Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke
Authors: Martin Ebinger, Benjamin Winter, Matthias Wendt, Joachim E. Weber, Carolin Waldschmidt, Michal Rozanski, Alexander Kunz, Peter Koch, Philipp A. Kellner, Daniel Gierhake, Kersten Villringer, Jochen B. Fiebach, Ulrike Grittner, Andreas Hartmann, Bruno-Marcel Mackert, Matthias Endres, Heinrich J. Audebert
Journal: JAMA (2014)

Time to thrombolysis is crucial for outcome in acute ischemic stroke.To determine if starting thrombolysis in a specialized ambulance reduces delays.In the Prehospital Acute Neurological Treatment and Optimization of Medical care in Stroke Study (PHANTOM-S), conducted in Berlin, Germany, we randomly assigned weeks with and without availability of the Stroke Emergency Mobile (STEMO) from May 1, 2011, to January 31, 2013. Berlin has an established stroke care infrastructure with 14 stroke units. We included 6182 adult patients (STEMO weeks: 44.3% male, mean [SD] age, 73.9 [15.0] y; control weeks: 45.2% male, mean [SD] age, 74.3 [14.9] y) for whom a stroke dispatch was activated.The intervention comprised an ambulance (STEMO) equipped with a CT scanner, point-of-care laboratory, and telemedicine connection; a stroke identification algorithm at dispatcher level; and a prehospital stroke team. Thrombolysis was started before transport to hospital if ischemic stroke was confirmed and contraindications excluded.Primary outcome was alarm-to-thrombolysis time. Secondary outcomes included thrombolysis rate, secondary intracerebral hemorrhage after thrombolysis, and 7-day mortality.Time reduction was assessed in all patients with a stroke dispatch from the entire catchment area in STEMO weeks (3213 patients) vs control weeks (2969 patients) and in patients in whom STEMO was available and deployed (1804 patients) vs control weeks (2969 patients). Compared with thrombolysis during control weeks, there was a reduction of 15 minutes (95% CI, 11-19) in alarm-to-treatment times in the catchment area during STEMO weeks (76.3 min; 95% CI, 73.2-79.3 vs 61.4 min; 95% CI, 58.7-64.0; P < .001). Among patients for whom STEMO was deployed, mean alarm-to-treatment time (51.8 min; 95% CI, 49.0-54.6) was shorter by 25 minutes (95% CI, 20-29; P < .001) than during control weeks. Thrombolysis rates in ischemic stroke were 29% (310/1070) during STEMO weeks and 33% (200/614) after STEMO deployment vs 21% (220/1041) during control weeks (differences, 8%; 95% CI, 4%-12%; P < .001, and 12%, 95% CI, 7%-16%; P < .001, respectively). STEMO deployment incurred no increased risk for intracerebral hemorrhage (STEMO deployment: 7/200; conventional care: 22/323; adjusted odds ratio [OR], 0.42, 95% CI, 0.18-1.03; P = .06) or 7-day mortality (9/199 vs 15/323; adjusted OR, 0.76; 95% CI, 0.31-1.82; P = .53).Compared with usual care, the use of ambulance-based thrombolysis resulted in decreased time to treatment without an increase in adverse events. Further studies are needed to assess the effects on clinical outcomes.clinicaltrials.gov Identifier: NCT01382862.
Cyclosporine A Inhibits the Adaptive Responses to Hypertonicity
Authors: David Sheikh-Hamad, Varsha Nadkarni, Yeong-Jin Choi, Luan D. Truong, Christi Wideman, Ramin Hodjati, Kenneth H. Gabbay
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Cell survival in the hypertonic environment of the renal medulla is dependent on the intracellular accumulation of protective organic solutes through the induction of genes whose transcriptional regulation is mediated in part by interaction between osmotic response elements and the transcription nuclear factor of activated T lymphocyte 5. It is shown that cyclosporine A (CsA) prevents the nuclear translocation of the transcription nuclear factor of activated T lymphocyte 5 and inhibits osmotic response element–mediated reporter gene expression. The expression of mRNA for hypertonicity-induced genes (aldose reductase, betaine/gamma-amino-n-butyric acid transporter 1, and heat shock protein 70) is also decreased in the medulla of CsA-treated rats. CsA inhibits the increase of betaine/gamma-amino-n-butyric acid transporter 1 and heat shock protein 70 mRNA in osmotically stressed MDCK cells, blocks cell proliferation under isotonic conditions, and augments hypertonicity-induced apoptosis. Histologic examination of the kidneys of CsA-treated rats shows a marked increase in apoptosis in the renal medulla where hypertonicity normally prevails. The data are consistent with calcineurin-mediated induction of hypertonic stress-response genes, and they suggest that CsA nephrotoxicity may in part result from inhibition of the adaptive responses to hypertonicity occurring during the urinary concentrating mechanism.
Partial trisomy of the long arm of chromosome 1 in myelofibrosis and polycythemia vera
Authors: Lillian Y. F. Hsu, Dona Pinchiaroli, Harriet S. Gilbert, Ruth Wittman, Kurt Hirschhorn
Journal: American Journal of Hematology (1977)

Abstract We have identified partial trisomy 1q in 2 patients with different hematologic disorders. The first patient was a 55‐year‐old female with myelosclerosis and myeloid metaplasia diagnosed at age 38 years presenting with anemia, fatigue, bruising, fever, and splenomegaly. At age 56, she had 50–95% myeloblast cells and 95–100 nucleated RBC precursors per 100 WBC. Chromosome analysis of unstimulated leukocytes with Q, G, and C banding showed 46,XX,‐6,+t(1;6) (q25;p22) in all metaphase cells. In vitro incorporation of Fe 55 was demonstrated in 90% of metaphases by autoradiography. The second patient, a 49‐year‐old male, was diagnosed as having polycythemia vera at age 30 during a regular checkup. He since developed hepatosplenomegaly. Chromosome analysis from a direct bone marrow preparation at age 44 and 45 showed grossly normal karyotypes. At age 49, his marrow by Q and G banding showed almost 100% of cells with 46,XY,–13,+t(1;13) (q12;p12). Eleven cases of trisomy of 1q have been reported in various hematologic disorders. It is apparent that partial trisomy 1q represents another nonrandom chromosomal abnormality, in addition to the most common nonrandom chromosomal aberrations, such as the Philadelphia chromosome, trisomy 8, trisomy 9, and monosomy 7 in hematologic disorders.
Norepinephrine Up-regulates the Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase (MMP)-2, and MMP-9 in Nasopharyngeal Carcinoma Tumor Cells
Authors: Eric V. Yang, Anil K. Sood, Min Chen, Yang Li, Tim D. Eubank, Clay B. Marsh, Scott Jewell, Nicholas A. Flavahan, Carl Morrison, Peir-En Yeh, Stanley Lemeshow, Ronald Glaser
Journal: Cancer Research (2006)

Abstract Recent studies using ovarian cancer cells have shown that the catecholamine hormones norepinephrine (norepi) and epinephrine (epi) may influence cancer progression by modulating the expression of matrix metalloproteinases (MMP) and vascular endothelial growth factor (VEGF). The purpose of this study is to determine if the stress hormone norepi can influence the expression of MMP-2, MMP-9, and VEGF in nasopharyngeal carcinoma (NPC) tumors by using three NPC tumor cell lines. The NPC cell lines HONE-1, HNE-1, and CNE-1 were treated with norepi. The effects of norepi on MMP-2, MMP-9, and VEGF synthesis were measured by ELISA; functional MMP activity was measured by the invasive potential of the cells using a membrane invasion culture system whereas functional activity of VEGF was analyzed using a human umbilical vein endothelial cell tube formation assay. Norepi treatment increased MMP-2, MMP-9, and VEGF levels in culture supernatants of HONE-1 cells, which could be inhibited by the β-blocker propranolol. Norepi induced the invasiveness of all NPC cell lines in a dose-dependent manner, which was blocked by CMT-3, an MMP inhibitor, and propranolol. Norepi stimulated the release of functional angiogenic VEGF by HONE-1 cells as well. Finally, HONE-1 cells were shown to express β-adrenergic receptors as did seven of seven NPC biopsies examined. The data suggest that catecholamine hormones produced by the sympathetic-adrenal medullary axis may affect NPC tumor progression, in part, through modulation of key angiogenic cytokines. (Cancer Res 2006; 66(21): 10357-64)
Do the competition rules of synchronized swimming encourage undesirable levels of hypoxia?
Authors: B N Davies, G C Donaldson, N Joels
Journal: British Journal of Sports Medicine (1995)

Recent anecdotal reports that some synchronized swimmers have become dizzy or disorientated towards the end of their performance, and in the worst cases fainted underwater, have caused concern. However, the rules of synchronized swimming encourage slow performance of compulsory figures, and an analysis of the competition placings and duration of underwater sequences showed that the highest rankings were gained by slowly performed compulsory figures and free programmes containing a long underwater sequence. The combination of breath-holding and the vigorous exercise involved suggests that some of the symptoms complained of by the swimmers might be due to hypoxia. We therefore studied the alveolar gas tensions in nine members of the Great Britain National Squad immediately following the performance of set figures and the initial underwater sequence of their free routine in a swimming-bath. All were cyanosed after the underwater sequences of the free routine and reported being mildly confused. The mean(s.d.) alveolar PO2 at this stage was 5.07(1.1) KPa, while three girls had an alveolar PO2 below 4 KPa, the lowest being 3.67 KPa. These gas tensions suggest that potentially dangerous levels of hypoxia may develop during competitive synchronized swimming and that prolonged underwent sequences should not be encouraged.
Proteomics of protein post-translational modifications implicated in neurodegeneration
Authors: Ru-Jing Ren, Eric B Dammer, Gang Wang, Nicholas T Seyfried, Allan I Levey
Journal: Translational Neurodegeneration (2014)

Mass spectrometry (MS)-based proteomics has developed into a battery of approaches that is exceedingly adept at identifying with high mass accuracy and precision any of the following: oxidative damage to proteins (redox proteomics), phosphorylation (phosphoproteomics), ubiquitination (diglycine remnant proteomics), protein fragmentation (degradomics), and other posttranslational modifications (PTMs). Many studies have linked these PTMs to pathogenic mechanisms of neurodegeneration. To date, identifying PTMs on specific pathology-associated proteins has proven to be a valuable step in the evaluation of functional alteration of proteins and also elucidates biochemical and structural explanations for possible pathophysiological mechanisms of neurodegenerative diseases. This review provides an overview of methods applicable to the identification and quantification of PTMs on proteins and enumerates historic, recent, and potential future research endeavours in the field of proteomics furthering the understanding of PTM roles in the pathogenesis of neurodegeneration.