tbuckley/cabot-search huggingface dataset:
Metabolic acidosis stimulates H+ secretion in the rabbit outer medullary collecting duct (inner stripe) of the kidney.
Authors: S Tsuruoka, G J Schwartz
Journal: Journal of Clinical Investigation (1997)

The outer medullary collecting duct (OMCD) absorbs HCO3- at high rates, but it is not clear if it responds to metabolic acidosis to increase H+ secretion. We measured net HCO3- transport in isolated perfused OMCDs taken from deep in the inner stripes of kidneys from control and acidotic (NH4Cl-fed for 3 d) rabbits. We used specific inhibitors to characterize the mechanisms of HCO3- transport: 10 microM Sch 28080 or luminal K+ removal to inhibit P-type H+,K+-ATPase activity, and 5-10 nM bafilomycin A1 or 1-10 nM concanamycin A to inhibit H+-ATPase activity. The results were comparable using either of each pair of inhibitors, and allowed us to show in control rabbits that 65% of net HCO3- absorption depended on H+-ATPase (H flux), and 35% depended on H+,K+-ATPase (H,K flux). Tubules from acidotic rabbits showed higher rates of HCO3- absorption (16.8+/-0.3 vs. 12.8+/-0.2 pmol/min per mm, P < 0.01). There was no difference in the H,K flux (5.9+/-0.2 vs. 5.8+/-0.2 pmol/min per mm), whereas there was a 61% higher H flux in segments from acidotic rabbits (11.3+/-0.2 vs. 7.0+/-0.2 pmol/min per mm, P < 0.01). Transport was then measured in other OMCDs before and after incubation for 1 h at pH 6.8, followed by 2 h at pH 7.4 (in vitro metabolic acidosis). Acid incubation in vitro stimulated HCO3- absorption (12.3+/-0.3 to 16.2+/-0.3 pmol/min per mm, P < 0.01), while incubation at pH 7.4 for 3 h did not change basal rate (11.8+/-0.4 to 11.7+/-0.4 pmol/min per mm). After acid incubation the H,K flux did not change, (4.7+/-0.4 to 4.6+/-0.4 pmol/min per mm), however, there was a 60% increase in H flux (6.6+/-0.3 to 10.8+/-0.3 pmol/min per mm, P < 0.01). In OMCDs from acidotic animals, and in OMCDs incubated in acid in vitro, there was a higher basal rate and a further increase in HCO3- absorption (16.7+/-0.4 to 21.3+/-0.3 pmol/min per mm, P < 0.01) because of increased H flux (11.5+/-0.3 to 15.7+/-0.2 pmol/min per mm, P < 0.01) without any change in H,K flux (5.4+/-0.3 to 5.6+/-0.3 pmol/min per mm). These data indicate that HCO3- absorption (H+ secretion) in OMCD is stimulated by metabolic acidosis in vivo and in vitro by an increase in H+-ATPase-sensitive HCO3- absorption. The mechanism of adaptation may involve increased synthesis and exocytosis to the apical membrane of proton pumps. This adaptation helps maintain homeostasis during metabolic acidosis.
Prevalence of self reported musculoskeletal diseases is high
Authors: H S J Picavet
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> To present the prevalence of self reported musculoskeletal diseases, the coexistence of these diseases, the test-retest reliability with six months in between, and the association with musculoskeletal pain symptoms. <b>Methods:</b> Twelve layman descriptions of common musculoskeletal diseases were part of the questionnaires of a prospective cohort study of a random sample in the general Dutch population aged 25 years or more (baseline: n=3664, follow up after six months: n=2338). Data collection also included information about pain relating to five different anatomical areas. <b>Results:</b> Osteoarthritis of the knee (men 10.1%, women 13.6%) was amongst the most reported musculoskeletal diseases, whereas the figures for self reported rheumatoid arthritis (RA) were 1.6% and 4.6% for men and women, respectively. The coexistence of these diseases is high: 47 of the 66 combinations were reported more often than would be expected if they were independent of each other (p&lt;0.05). For most diseases the test-retest reliability was good (κ between 0.6 and 0.8), but for repetitive strain injury (κ=0.37) and chronic arthritis other than RA (κ=0.44) the agreement was fair to moderate. All complaints of pain were more often reported by those with musculoskeletal diseases than those without those diseases, and the pain pattern was disease-specific. <b>Conclusions:</b> Self reported musculoskeletal diseases are highly prevalent, with a fair to good reliability and a disease-specific pain pattern. Health surveys are a limited but valuable source of information for this group of health problems, which is not available from most other sources of information.
Allergic and non-allergic rhinitis in swimmers: clinical and cytological aspects
Authors: Matteo Gelardi, Maria Teresa Ventura, Raffaele Fiorella, Maria Luisa Fiorella, Cosimo Russo, Teresa Candreva, Antonella Carretta, Giovanni Passalacqua
Journal: British Journal of Sports Medicine (2010)

Rhinitis, either allergic or non-allergic, is frequent in athletes, particularly in swimmers. In this latter case, exposure to chlorine in swimming pools seems to play a relevant role, since it can exacerbate a pre-existing allergic rhinitis (AR) or produce a non-specific irritation. The aim of this study was to detail the clinical and cytological characteristics of rhinitis in swimmers, and to assess the possible role of chlorine-induced symptoms.Elite swimmers with rhinitis symptoms underwent a complete diagnostic work-up, including allergy testing, nasal cytology and anterior rhinomanometry. Those evaluations were repeated after 1 month of use of a nasal clip during swimming. A matched group of asymptomatic swimmers was also studied. A total of 74 swimmers (54 symptomatic and 20 controls), with an age range of 9-21 years, were studied. In the control group, only mild and non-specific findings were observed, and only two had a positive skin test.In the symptomatic group, 24 (44%) had AR, and 19 (35%) had a predominant neutrophilic inflammation. The use of a nose clip reduced cellular infiltration and nasal resistances only in the subjects with neutrophilic rhinitis, whereas a clinical improvement was seen also in AR.A neutrophilic rhinitis occurs in a large proportion of swimmers. This seems to be irritative in its nature and can be prevented by avoiding the direct contact with chlorinated water.
Angiogenesis in gastric ulcers: impaired in patients taking non-steroidal anti-inflammatory drugs.
Authors: N Hudson, M Balsitis, S Everitt, C J Hawkey
Journal: Gut (1995)

Non-steroidal anti-inflammatory drug (NSAID) therapy is associated with delayed gastroduodenal ulcer healing. In rats the degree of angiogenesis (new vessel formation) within the ulcer bed correlates strongly with the extent and speed of ulcer healing and may be inhibited by NSAIDs. This study therefore assessed the vascularity of 38 antral gastric ulcers immunohistochemically, using CD31 a vascular endothelial cell marker, in 17 patients taking NSAIDs and 19 control patients. In the superficial granulation tissue NSAID therapy was associated with a significant reduction in the median number of capillaries (13.5 (IQR: 9.5-18) v 23.5 (14-31) (p < 0.005)), number of vessel buds (6 (4-12.5) v 17 (12-23) (p < 0.05)), and maximum vessel diameter (29 (20.75-30.75) v 33.75 (24-45) (p < 0.05)) when compared with controls. In deep granulation tissue NSAID therapy was similarly associated with a significant reduction in the number of capillaries (9 (6.5-12) v 14 (9-19.25) (p < 0.04)), number of vessel buds (5 (3.5-8.5) v 13 (7-16.5) (p < 0.01)), and maximum vessel diameter (23 (18-20.5) v 33 (21.5-45) (p < 0.02)). There were no differences in vascularity in the adjacent glandular mucosa. Impairment of angiogenesis may be an important mechanism of NSAID related delayed ulcer healing.
Association of Enhanced Limbic Response to Threat With Decreased Cortical Facial Recognition Memory Response in Schizophrenia
Authors: Theodore D. Satterthwaite, Daniel H. Wolf, James Loughead, Kosha Ruparel, Jeffrey N. Valdez, Steven J. Siegel, Christian G. Kohler, Raquel E. Gur, Ruben C. Gur
Journal: American Journal of Psychiatry (2010)

Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia.Blood-oxygen-level-dependent response was examined by means of functional magnetic resonance imaging (3 Tesla) in healthy comparison subjects (N=21) and in patients with schizophrenia (N=12) or schizoaffective disorder, depressed type (N=4), during a two-choice recognition task that used images of human faces. Each target face, previously displayed with a threatening or nonthreatening affect, was displayed with neutral affect. Responses to successful recognition and responses to the effect of previously threatening versus nonthreatening affect were evaluated, and correlations with symptom severity (total Brief Psychiatric Rating Scale score) were examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory.Patients performed the task more slowly than healthy comparison subjects. Comparison subjects recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Comparison subjects exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed weakening of this relationship.Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between these two brain systems that are often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia.
Triggering Myocardial Infarction by Marijuana
Authors: Murray A. Mittleman, Rebecca A. Lewis, Malcolm Maclure, Jane B. Sherwood, James E. Muller
Journal: Circulation (2001)

Background —Marijuana use in the age group prone to coronary artery disease is higher than it was in the past. Smoking marijuana is known to have hemodynamic consequences, including a dose-dependent increase in heart rate, supine hypertension, and postural hypotension; however, whether it can trigger the onset of myocardial infarction is unknown. Methods and Results —In the Determinants of Myocardial Infarction Onset Study, we interviewed 3882 patients (1258 women) with acute myocardial infarction an average of 4 days after infarction onset. We used the case-crossover study design to compare the reported use of marijuana in the hour preceding symptoms of myocardial infarction onset to its expected frequency using self-matched control data. Of the 3882 patients, 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of myocardial infarction symptoms. Compared with nonusers, marijuana users were more likely to be men (94% versus 67%, P &lt;0.001), current cigarette smokers (68% versus 32%, P &lt;0.001), and obese (43% versus 32%, P =0.008). They were less likely to have a history of angina (12% versus 25%, P &lt;0.001) or hypertension (30% versus 44%, P =0.002). The risk of myocardial infarction onset was elevated 4.8 times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes after marijuana use. The elevated risk rapidly decreased thereafter. Conclusions —Smoking marijuana is a rare trigger of acute myocardial infarction. Understanding the mechanism through which marijuana causes infarction may provide insight into the triggering of myocardial infarction by this and other, more common stressors.
Effectiveness of the Maze Procedure Using Cooled-Tip Radiofrequency Ablation in Patients With Permanent Atrial Fibrillation and Rheumatic Mitral Valve Disease
Authors: Carlos A.C. Abreu Filho, Luiz A.F. Lisboa, Luís A.O. Dallan, Guilherme Sobreira Spina, Max Grinberg, Maurício Scanavacca, Eduardo A. Sosa, José Antonio F. Ramires, Sérgio A. Oliveira
Journal: Circulation (2005)

Background— Although the Cox-Maze III procedure is effective for treating permanent atrial fibrillation (AF), its high complexity limits its use. The Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) System is an alternative source of energy used to ablate AF. The aim of this study was to evaluate the effectiveness of the SICTRA for the treatment of permanent AF in patients with rheumatic mitral valve (MV) disease. Methods and Results— Between February 2002 and April 2003, 70 patients with permanent AF and rheumatic MV disease were randomly assigned to undergo a modified Maze III procedure using SICTRA associated with MV surgery (group A) or MV surgery alone (group B). Groups A and B were similar in terms of baseline characteristics. The in-hospital mortality rate was 2.3% (1 death) in group A versus 0% (no deaths) in group B ( P &gt;0.99). The additional time required for the left-sided radiofrequency ablation in group A was 14.2±5.1 minutes and for right-sided ablation was 12.3±4.2 minutes. The mean postoperative follow-up periods were 13.8±3.4 and 11.5±7.3 months, respectively, in groups A and B. The overall mid-term survival rate was 95.1% in group A and 92.8% in group B ( P &gt;0.99). The cumulative rates of sinus rhythm were 79.4% in group A and 26.9% in group B ( P =0.001). Doppler echocardiography documented biatrial transport function in 90.3% of group A patients in sinus rhythm. Conclusions— The SICTRA is effective for treating permanent AF associated with rheumatic MV disease.
P58 What does pulmonary tuberculosis (TB) look like in London?
Authors: C. Brown, S. Natas, A. Salam, R. Breen
Journal: Thorax (2010)

<h3>Introduction</h3> A typical radiological presentations of TB may lead to unnecessary and costly tests, delayed or missed diagnoses, and increased transmission. Feeling that such presentations were increasing, we retrospectively reviewed our thoracic TB patients9 radiology. <h3>Methods</h3> The London TB Register (LTBR) was queried for patients at our Trust with intrathoracic lymph node or pleural disease (January 2006–December 2008), or pulmonary disease (January 2008–December 2008). Chest radiographs (CXRs) and CT scans from symptom onset to diagnosis were analysed by a consultant radiologist. Clinical data was obtained from hospital records. <h3>Results</h3> 118 patients were identified: male=75 (64%); median age=33 years; HIV-infected=10 (8%). 118 (100%) had CXRs and 57 (48%) additional CTs. From LTBR 16 had intrathoracic lymphadenopathy, 16 pleural diseases, 73 pulmonary diseases, and three mixed. One pre-diagnosis CXR was performed in 7/10 (70%) HIV-positive and 63/108 (58%) HIV-negative/unknown; two in 3/10 (30%) HIV-positive, 27/108 (25%) HIV-negative/unknown; &gt;3 CXR (maximum eight) were performed in 18/108 (17%) HIV-negative/unknown. We focused on radiologically pneumonic cases. 63/118 (53%) had consolidation on initial CXR, 66/118 (56%) on final. 29/66 (44%) had multifocal disease; all but 8/29 (28%) had either lymphadenopathy, cavitation, or nodules. 37/66 (56%) had disease in one zone (see Abstract P58 Table 1). 18/37 (49%) were right UZ; eight with/without pleural involvement but no other suggestive features such as cavitation or nodularity. 7/37 (19%) were left UZ patients; 4/7 (57%) with no other suggestive features. 8/37 (22%) had solely LZ consolidation; 2/8 (25%) with no other suggestive features. Of 17 presentations that could mimic standard pneumonia (zonal disease with/without pleural involvement but no suggestive TB features) one was HIV positive; 15 had sputum samples—4/15 (27%) were smear positive, 12/15 (80%) were culture positive. Progression to CT was 10/17 (59%). With any consolidation, 20/32 (63%) CTs accessible yielded additional information, often minimal (e.g. 14/32 (44%) showed nodules in addition to lymphadenopathy). 13/32 (41%) were women, 9/13 (69%) under 40-years-old. <h3>Discussion</h3> In our cohort the majority of patients had typical diagnostic features on presenting CXR. Lower zone cases were not uncommon but most had features suggestive of TB. The high frequency of CT with questionable clinical gain and high radiation exposure, particularly in young women, is of concern.
Targeting the Molecular Chaperone Heat Shock Protein 90 Provides a Multifaceted Effect on Diverse Cell Signaling Pathways of Cancer Cells
Authors: Wanping Xu, Len Neckers
Journal: Clinical Cancer Research (2007)

Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of several conditionally activated and/or expressed signaling proteins as well as multiple mutated, chimeric, and/or overexpressed signaling proteins, which promote cancer cell growth and/or survival (see
The role of nitric oxide in endothelium-dependent vasodilation of hypercholesterolemic patients.
Authors: P R Casino, C M Kilcoyne, A A Quyyumi, J M Hoeg, J A Panza
Journal: Circulation (1993)

Patients with hypercholesterolemia have a reduced response to endothelium-dependent vasodilators. However, the regulatory function of the endothelium on vascular tone is mediated through the release of several vasoactive substances; therefore, a reduced response to endothelium-dependent agents does not identify which of the factors released by the endothelium is involved in this abnormality.To investigate the role of nitric oxide in the endothelium-dependent vasodilation in hypercholesterolemia, we studied the effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelial nitric oxide synthesis, on basal vascular tone and on the responses to acetylcholine, an endothelium-dependent vasodilator, and to sodium nitroprusside, a direct smooth muscle dilator. The study included 33 hypercholesterolemic patients (17 men; 51 +/- 8 years; plasma cholesterol, > or = 240 mg/dL) and 23 normal controls (12 men; 48 +/- 7 years; plasma cholesterol, < 210 mg/dL). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain-gauge plethysmography. Basal blood flow and vascular resistance were similar in hypercholesterolemic patients and normal controls (3.1 +/- 1 versus 2.6 +/- 0.8 mL/min per 100 mL and 32.1 +/- 13 versus 36.1 +/- 12 mm Hg/mL-1.min-1.100 mL-1, respectively). The reduction in basal blood flow and increase in vascular resistance produced by L-NMMA were not significantly different between the two groups. L-NMMA markedly blunted the response to acetylcholine in normals (maximum flow decreased from 16.4 +/- 8 to 7.0 +/- 3; P < .005); however, the arginine analogue did not significantly modify the response to acetylcholine in the hypercholesterolemic patients (maximum flow, 11.1 +/- 8 versus 10.0 +/- 8). L-NMMA did not modify the vasodilator response to sodium nitroprusside in either controls or patients.These findings indicate that hypercholesterolemic patients have a defect in the bioactivity of nitric oxide that may explain their impaired endothelium-dependent vascular relaxation.
Medium‐sized peptides as built in carriers for biologically active compounds
Authors: Ferenc Hudecz, Zoltán Bánóczi, Gabriella Csík
Journal: Medicinal Research Reviews (2005)

A growing number of oligopeptides of natural and/or synthetic origin have been described and considered as targeting structures for delivery bioactive compounds into various cell types. This review will outline the discovery of peptide sequences and the corresponding mid-sized oligopeptides with membrane translocating properties and also summarize de novo designed structures possessing similar features. Conjugates and chimera constructs derived from these sequences with covalently attached bioactive peptide, epitope, oligonucleotide, PNA, drug, reporter molecule will be reviewed. A brief note will refer to the present understanding on the uptake mechanism at the end of each section.
Pseudomonas aeruginosa abscess masquerading as a slowly growing solitary pulmonary nodule
Authors: C. W. Zwillich, J. H. Ellis
Journal: Thorax (1974)

<b>Zwillich, C. W. and Ellis, J. H. (1974).</b><i>Thorax</i>, <b>29,</b> 603-606. <i>Pseudomonas aeruginosa</i><b>abscess masquerading as a slowly growing solitary pulmonary nodule.</b> A case of slowly growing pulmonary nodule due to <i>Pseudomonas aeruginosa</i> is reported. This nodule was present on chest radiographs over a 20-year period.
Single-Nucleotide Polymorphisms in p53 Pathway and Aggressiveness of Prostate Cancer in a Caucasian Population
Authors: Tong Sun, Gwo-Shu Mary Lee, William K. Oh, Mark Pomerantz, Ming Yang, Wanling Xie, Matthew L. Freedman, Philip W. Kantoff
Journal: Clinical Cancer Research (2010)

The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. Mdm2, Mdm4, and Hausp are all critical regulators of the p53 protein. Despite the importance of the p53 pathway in prostate cancer development and progression, little is known about the association of functional single-nucleotide polymorphisms (SNP) in the p53 pathway genes and prostate cancer aggressiveness.In this study, we analyze the association of SNPs in p53, Mdm2, Mdm4, and Hausp genes with prostate cancer clinicopathologic variables in a large hospital-based Caucasian prostate cancer cohort (N = 4,073).We found that the Mdm2 SNP309 T allele was associated with earlier onset prostate cancer (P = 0.004), higher Gleason scores (P = 0.004), and higher stages in men undergoing a radical prostatectomy (P = 0.011). Both the Mdm4 and Hausp SNPs (rs1380576 and rs1529916) were found to be associated with higher D'Amico risk prostate cancer category at the time of diagnosis (P = 0.023 and P = 0.046, respectively). Mdm4 SNP was also found to be associated with higher Gleason score at radical prostatectomy (P = 0.047). We did not observe any statistically significant association between the p53 Arg72Pro polymorphism and prostate cancer aggressiveness or pathologic variables.These results suggested the importance of these p53 regulators in prostate cancer development and progression.
Caloric restriction and gender modulate cardiac muscle mitochondrial H2O2 production and oxidative damage
Authors: B COLOM, J OLIVER, P ROCA, F GARCIAPALMER
Journal: Cardiovascular Research (2007)

Gender and diet have an important effect in cardiovascular disease and other aging-associated disorders, whose initiation and/or worsening seem to be delayed in females from different species and in animals subjected to caloric restriction (CR). The aim of the present study was to investigate whether cardiac muscle bioenergetic mitochondrial features could be responsible for these beneficial effects.Fifteen-month-old male and female Wistar rats were fed ad libitum or subjected to 40% CR for 3 months. Cardiac mitochondrial function (citrate synthase activity, oxygen consumption), activity of complexes I, III, IV and ATPase of the OXPHOS system, antioxidant activities (MnSOD, GPx), mitochondrial DNA and protein content, mitochondrial H2O2 production, heart oxidative damage, complex IV and ATPase content and efficiency, as well as protein levels of mitochondrial transcription factor A (TFAM) and peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC1alpha) were measured.Female and CR rats exhibited lower cardiac mitochondria content, which were more efficient and generated less H2O2 than in males and ad libitum fed animals, with their consequent lower heart oxidative damage.Higher mitochondrial differentiation becomes a metabolic adaptation to increase energy efficiency, as what happens in female and CR rats. This adaptation is associated with their lower mitochondrial free radical production and oxidative damage, which could help to understand the mechanism by which these animals exhibit a lower incidence of aging-related disorders, including cardiovascular disease.