tbuckley/cabot-search huggingface dataset:
Pulmonary arterial hypertension in systemic sclerosis: diagnostic pathway and therapeutic approach
Authors: L Robertson
Journal: Annals of the Rheumatic Diseases (2005)

### Case 1

A 63 year old white woman was admitted to hospital in February 2000 owing to rapidly increasing dyspnoea on exertion (NYHA III), chest pain, and fever. The presence of sclerodactyly with loss of distal parts of the fingers, and megacapillaries at capillaroscopy, allowed the diagnosis of limited cutaneous systemic sclerosis (fig 1). Physical examination also disclosed crackles in the lower lobes of the lungs, systolic murmur with loud pulmonary second sound, and feet oedema.



 Figure 1  
 Case 1. (A) Chest x ray findings show bibasilar reticular opacities, cardiomegaly with accentuation of the right ventricle, and enlargement of the pulmonary artery, which are consistent with interstitial lung disease and pulmonary hypertension. (B) High resolution CT of the lungs discloses features of interstitial lung disease with “ground glass” opacities and widening of the central blood vessels. (C) Doppler echocardiography shows blood regurgitation through the tricuspid valve, which allows estimation of PASP. (D) Perfusion scintigraphy of the lungs carried out in February 2000 (D/1) shows redistribution of the blood flow into the upper parts of the lungs and irregular areas of diminished blood flow in the peripheral parts of the lungs consistent with PAH and pulmonary thromboembolism. For comparison, perfusion scintigraphy of the lungs carried out in June 2000 (D/2) shows a significant increase in blood flow in the lower parts of both lungs, which paralleled a decrease in PASP as measured with Doppler echocardiography.



Laboratory tests included high erythrocyte sedimentation rate (145 mm/1st h), C reactive protein (2530 mg/l, normal <100 mg/l), presence of antinuclear antibodies (1/1280 and speckled pattern on indirect immunofluorescence), mild anaemia and thrombocytopenia (platelet count of 115×109/l), decreased arterial oxygen and carbon dioxide pressures. A chest x ray examination showed cardiomegaly, dilatation of the main pulmonary artery (fig 1), centralisation of pulmonary vascular flow, and reticular opacities in …
A new AluI satellite DNA in the root-knot nematode Meloidogyne fallax: relationships with satellites from the sympatric species M. hapla and M. chitwoodi
Authors: P. Castagnone-Sereno, J. P. Semblat, F. Leroy, P. Abad
Journal: Molecular Biology and Evolution (1998)

A highly abundant satellite DNA comprising 20% of the Meloidogyne fallax (Nematoda, Tylenchida) genome was cloned and sequenced. The satellite monomer is 173 bp long and has a high A + T content of 72.3%, with frequent runs of A's and T's. The sequence variability of the monomers is 2.7%, mainly due to random distribution of single-point mutations. A search for evidence of internal repeated subunits in the monomer sequence revealed a 6-bp motif (AAATTT) for which five degenerated repeats, differing by just a single base pair, could be identified. Pairwise comparison of the M. fallax satellite with those from the sympatric species Meloidogyne chitwoodi and Meloidogyne hapla revealed a high sequence similarity (68.39%) with one satellite DNA subfamily in M. chitwoodi, which indicated an unexpected close relationship between them. Given the high copy number and the extreme sequence homogeneity among monomeric units, it may be assumed that the satellite DNA of M. fallax could have evolved through some recent and extensive amplification burst in the nematode genome. In this case, its relatively short life would not yet have allowed the accumulation of random mutations in independent amplified repeats. Considering the morphological resemblance between the two species and their ability to produce interspecific fertile hybrids under controlled conditions, these results indicate that M. fallax may share a common ancestor with M. chitwoodi, from which it could have diverged recently. All these data suggest that M. fallax could be the result of a recent speciation process and show that Meloidogyne satellite DNAs may be of interest to resolve phylogenetic relationships among closely related species from this genus.
One-Year Comparison of a High–Monounsaturated Fat Diet With a High-Carbohydrate Diet in Type 2 Diabetes
Authors: Bonnie J. Brehm, Barbara L. Lattin, Suzanne S. Summer, Jane A. Boback, Gina M. Gilchrist, Ronald J. Jandacek, David A. D’Alessio
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to compare the effects of high–monounsaturated fatty acid (MUFA) and high-carbohydrate (CHO) diets on body weight and glycemic control in men and women with type 2 diabetes. RESEARCH DESIGN AND METHODS—Overweight/obese participants with type 2 diabetes (n = 124, age = 56.5 ± 0.8 years, BMI = 35.9 ± 0.3 kg/m2, and A1C = 7.3 ± 0.1%) were randomly assigned to 1 year of a high-MUFA or high-CHO diet. Anthropometric and metabolic parameters were assessed at baseline and after 4, 8, and 12 months of dieting. RESULTS—Baseline characteristics were similar between the treatment groups. The overall retention rate for 1 year was 77% (69% for the high-MUFA group and 84% for the high-CHO group; P = 0.06). Based on food records, both groups had similar energy intake but a significant difference in MUFA intake. Both groups had similar weight loss over 1 year (−4.0 ± 0.8 vs. −3.8 ± 0.6 kg) and comparable improvement in body fat, waist circumference, diastolic blood pressure, HDL cholesterol, A1C, and fasting glucose and insulin. There were no differences in these parameters between the groups. A follow-up assessment of a subset of participants (n = 36) was conducted 18 months after completion of the 52-week diet. These participants maintained their weight loss and A1C during the follow-up period. CONCLUSIONS—In individuals with type 2 diabetes, high-MUFA diets are an alternative to conventional lower-fat, high-CHO diets with comparable beneficial effects on body weight, body composition, cardiovascular risk factors, and glycemic control.
Cell Transplantation as Future Therapy for Cardiovascular Disease?
Authors: Leslie Reinlib, Loren Field
Journal: Circulation (2000)

Despite the development of improved therapies and the significant advances in the understanding of the basis of disease pathogenesis, millions of Americans continue to live with life-threatening cardiovascular diseases. Recent breakthroughs suggest exciting directions that are likely to produce more effective therapies for the treatment of cardiovascular disease. One such area, cell transplantation (grafting of healthy cells into the diseased heart), holds enormous potential as an approach to cardiovascular pathophysiology. Once thought to be a scientific long shot, cell transplantation is becoming recognized as a viable strategy to strengthen weak hearts and limit infarct growth. The technology could also be used for the long-term delivery of beneficial recombinant proteins to the heart, which is a strategy to complement molecular biology advances and provide an alternative strategy for gene therapy. On August 24, 1998, the National Heart, Lung, and Blood Institute convened a workshop to discuss the current status of this fast-moving line of research and to explore its promise for treating cardiovascular disease. The participants included basic and clinical researchers, with representatives from academic and commercial research settings. The workshop was designed to establish the state-of-the-art and to equate current research with practical clinical application. The group recommended short- and long-term goals to assist in realizing, in the most expedient manner, the potential utility of cell transplantation for the treatment of cardiovascular disease. A summary of the meeting discussions and recommendations for future areas of research is presented.
P161 Cough Intensity in Voluntary, Induced and Spontaneous Cough: Abstract P161 Table 1
Authors: KK Lee, K Ward, E Raywood, J Moxham, GF Rafferty, SS Birring
Journal: Thorax (2012)

<h3>Introduction</h3> Cough intensity is an important determinant of cough severity. We set out to investigate and compare the physiological characteristics and intensity of voluntary (VC), induced (IC) and spontaneous cough (SC) in subjects with chronic cough. <h3>Methods</h3> 28 subjects with chronic cough (17 female, mean age 57 years) underwent measurement of oesophageal pressure (Poes), gastric pressure (Pga), normalised peak cough flow rate (PCFR) and peak abdominal electromyographic activity (EMG) were measured during (1) maximum VC (MVC), (2) capsaicin IC (2 doses: C5 and supra-C5; 1st effort in a bout) and (3) SC (mean of 1st efforts of all bouts), in a subset of patients (n=9). Cough efforts were categorised as bouts or single events and as true cough or expiratory reflex (ER: absence of preparatory inspiration). <h3>Results</h3> MVC by definition was always a single effort and all efforts were true coughs; no subject initiated an ER during MVC manoeuvres. The majority of efforts in IC (C5) and SC occurred within coughing bouts. ERs were the most frequent type of efforts in both IC and SC, 61–67% of all efforts, but accounted for only one third of the initial efforts of bouts in both IC and SC; true cough was the most frequent 1st effort (Table 1). Cough intensity was greatest in MVC for all measures. Poes, Pga and EMGabd were similar for IC and SC, and were approximately 60–70% of MVC intensity. PCFR:PEFRp however, was significantly higher in SC compared to IC. The analysis was similar for supra-C5 stimulus with capsaicin. When restricted to the subgroup that underwent studies of all cough models (VC, IC and SC), the analysis was also similar. <h3>Conclusions</h3> This is the first study of the physiology of cough in patients with chronic cough and spontaneous cough. MVC produces the most intense cough. The type of cough effort in IC and SC is similar but there were important differences in cough intensity (flow). The reason for this and its implications for the induced cough model are unclear and warrant further investigation.
OUTBREAK OF ACUTE HEPATITIS CAUSED BY AFLATOXIN POISONING IN KENYA
Authors: Augustine Ngindu, PatrickR. Kenya, DavidM. Ocheng, ThomasN. Omondi, William Ngare, David Gatei, BruceK. Johnson, JuliusA. Ngira, Helen Nandwa, AdrianJ. Jansen, JasonN. Kaviti, Timothy Arap Siongok
Journal: The Lancet (1982)
Mechanical Stiffness Grades Metastatic Potential in Patient Tumor Cells and in Cancer Cell Lines
Authors: Vinay Swaminathan, Karthikeyan Mythreye, E. Tim O'Brien, Andrew Berchuck, Gerard C. Blobe, Richard Superfine
Journal: Cancer Research (2011)

Cancer cells are defined by their ability to invade through the basement membrane, a critical step during metastasis. While increased secretion of proteases, which facilitates degradation of the basement membrane, and alterations in the cytoskeletal architecture of cancer cells have been previously studied, the contribution of the mechanical properties of cells in invasion is unclear. Here, we applied a magnetic tweezer system to establish that stiffness of patient tumor cells and cancer cell lines inversely correlates with migration and invasion through three-dimensional basement membranes, a correlation known as a power law. We found that cancer cells with the highest migratory and invasive potential are five times less stiff than cells with the lowest migration and invasion potential. Moreover, decreasing cell stiffness by pharmacologic inhibition of myosin II increases invasiveness, whereas increasing cell stiffness by restoring expression of the metastasis suppressor TβRIII/betaglycan decreases invasiveness. These findings are the first demonstration of the power-law relation between the stiffness and the invasiveness of cancer cells and show that mechanical phenotypes can be used to grade the metastatic potential of cell populations with the potential for single cell grading. The measurement of a mechanical phenotype, taking minutes rather than hours needed for invasion assays, is promising as a quantitative diagnostic method and as a discovery tool for therapeutics. By showing that altering stiffness predictably alters invasiveness, our results indicate that pathways regulating these mechanical phenotypes are novel targets for molecular therapy of cancer.
Erythrocyte survival in chronic renal failure. Role of secondary hyperparathyroidism.
Authors: M Akmal, N Telfer, A N Ansari, S G Massry
Journal: Journal of Clinical Investigation (1985)

The human erythrocyte (RBC) is a target organ for parathyroid hormone (PTH) and the hormone increases RBC osmotic fragility and induces their hemolysis. The present study was undertaken to examine whether elevated blood levels of PTH affect RBC survival, and therefore whether PTH, being an extracorpuscular factor, is responsible for the shortened RBC survival in chronic renal failure. 51Cr-labeled RBC survival was elevated in six normal dogs, in six animals with chronic renal failure and secondary hyperparathyroidism (NPX), and in six thyroparathyroidectomized dogs (NPX-TPTX) with comparable degree and duration of chronic renal failure. In the normal dogs, 51Cr-labeled RBC survival ranged between 22 and 35 (25.6 +/- 1.9) d. In the NPX dogs, 51Cr-labeled RBC survival was shortened and the values ranged between 16 and 20 (18.4 +/- 0.6) d, a value significantly (P less than 0.01) lower than normal dogs. In NPX-TPTX dogs, 51Cr-labeled RBC survival ranged between 20 and 33 (25.2 +/- 1.8) d, a value not different from that in normal dogs but significantly higher (P less than 0.01) than that in NPX animals. Our data demonstrate that excess blood levels of PTH and not other consequences of the uremic state are responsible for the shortened RBC survival in chronic renal failure.
Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation
Authors: Zhaoqing Ding, Vidhu Mathur, Peggy P. Ho, Michelle L. James, Kurt M. Lucin, Aileen Hoehne, Haitham Alabsi, Sanjiv S. Gambhir, Lawrence Steinman, Jian Luo, Tony Wyss-Coray
Journal: The Journal of Experimental Medicine (2014)

Aberrant microglial responses contribute to neuroinflammation in many neurodegenerative diseases, but no current therapies target pathogenic microglia. We discovered unexpectedly that the antiviral drug ganciclovir (GCV) inhibits the proliferation of microglia in experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis (MS), as well as in kainic acid–induced excitotoxicity. In EAE, GCV largely prevented infiltration of T lymphocytes into the central nervous system (CNS) and drastically reduced disease incidence and severity when delivered before the onset of disease. In contrast, GCV treatment had minimal effects on peripheral leukocyte distribution in EAE and did not inhibit generation of antibodies after immunization with ovalbumin. Additionally, a radiolabeled analogue of penciclovir, [18F]FHBG, which is similar in structure to GCV, was retained in areas of CNS inflammation in EAE, but not in naive control mice, consistent with the observed therapeutic effects. Our experiments suggest GCV may have beneficial effects in the CNS beyond its antiviral properties.
Role of High Glucose-Induced Nuclear Factor-κB Activation in Monocyte Chemoattractant Protein-1 Expression by Mesangial Cells
Authors: Hunjoo Ha, Mi Ra Yu, Yoon Jin Choi, Masanori Kitamura, Hi Bahl Lee
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Although high glucose (HG) has been shown to induce nuclear factor-κB (NF-κB) activation in vascular cells, the upstream regulation and the biologic significance of NF-κB activation in diabetic renal injury are not clear. It was, therefore, examined if HG-induced generation of reactive oxygen species (ROS) and protein kinase C (PKC) activation are involved in NF-κB activation in mesangial cells (MC), and the role of NF-κB activation in HG-induced monocyte chemoattractant protein-1 (MCP-1) expression by MC was further investigated. Recent observations suggest that MCP-1 may play a role in the development and progression of diabetic nephropathy. HG rapidly induced NF-κB activation in MC as estimated by electrophoretic mobility shift assay. Supershift assay suggests that most of the binding activity arose from p50/p50 and p50/p65 dimers. Antioxidants, pyrrolidine dithiocarbamate, N-acetyl-L-cystein, and trolox effectively inhibited HG-induced NF-κB activation in MC. HG rapidly generated dichlorofluorescin-sensitive intracellular ROS in MC as measured by laser-scanning confocal microscopy. HG also activated PKC rapidly in MC. Inhibition of PKC effectively blocked HG-induced intracellular ROS generation and NF-κB activation in MC. HG increased MCP-1 mRNA expression by 1.9-fold and protein secretion by 1.6-fold that of control glucose in MC transfected with control vector but not in MC transfected with dominant negative mutant inhibitor of NF-κB (IκBαM). Inhibition of either PKC or ROS effectively blocked HG-induced, but not basal, MCP-1 protein secretion by MC transfected with control vector. Thus this study demonstrates that HG rapidly activates NF-κB in MC through PKC and ROS and suggests that HG-induced NF-κB activation in MC may play a role in diabetic renal injury through upregulation of MCP-1 mRNA and protein expression.
P129 Lung clearance index (LCI) is a sensitive marker of early airway changes in smokers with normal spirometry
Authors: N. J. Bell, A. R. Horsley, P. A. Reid, H. S. Sheridan, M. Monaghan, H. Connelly, A. P. Greening, J. A. Innes
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Abnormalities in indices of gas mixing derived from multiple breath nitrogen washouts have been demonstrated in smokers without spirometric evidence of airflow obstruction, which improved on smoking cessation. We report initial data from a study investigating the ability of a simpler measure of gas mixing, Lung Clearance Index (LCI), derived from multiple breath washouts using sulphur hexafluoride as tracer gas and a modified Innocor gas analyser, to detect early airway changes in smokers with normal spirometry. <h3>Methods</h3> Current cigarette smokers with a smoking history of over 10 pack years and no known cardiac or respiratory disease were recruited from smoking cessation clinics. Spirometry was performed to ERS standards before and after salbutamol. Participants with post-bronchodilator FEV<sub>1</sub>&lt;80% predicted, FEV<sub>1</sub>/FVC&lt;0.7, or a significant bronchodilator response were excluded from analysis. St George9s Respiratory Questionnaire (SGRQ) was completed. LCI reported is the mean of at least two technically acceptable repeat measurements. <h3>Results</h3> 17 participants remained after exclusions, mean age 44 years (range 31–57) and mean smoking history of 25 pack years (range 11–60). Mean (SD) post-bronchodilator FEV<sub>1</sub> and FEF<sub>25–75</sub> was 101 (12) and 80 (23)% predicted respectively. Only one participant had FEF<sub>25–75</sub>&lt;60%. There was a moderate negative correlation between smoking history and FEF<sub>25–75</sub> (r=−0.51, p=0.037) but not between smoking history and FEV<sub>1</sub>. Mean (SD) LCI was 7.7 (0.98) with mean (SD) intra-visit coefficient of variation of 3.7 (2.5)%. Eight participants had LCI&gt;7.5 (95% CI for LCI in normal subjects 5.9–7.5), suggesting impaired lung gas mixing. There was a negative correlation between LCI and FEV<sub>1</sub> (r=−0.55, p=0.02) and between LCI and FEF<sub>25–75</sub> (r=−0.66, p=0.004) but no significant correlation between LCI and smoking history or total SGRQ score. Mean (SD) total SGRQ score was 10.9 (7.5), 12 participants scoring over 7 (95% CI for total SGRQ score in normal subjects 5–7). Total SGRQ did not correlate with smoking history, LCI, FEV<sub>1</sub> or FEF<sub>25–75</sub>. <h3>Conclusions</h3> These data support the hypothesis that LCI is a sensitive marker of early airway changes in smokers with normal FEV<sub>1</sub> and FEF<sub>25–75</sub>. The effects of smoking cessation on this measure are currently being investigated.
Chronic cor pulmonale in pulmonary sarcoidosis.
Authors: J P Battesti, R Georges, F Basset, G Saumon
Journal: Thorax (1978)

Right-heart overload happens relatively rarely in sarcoidosis, even with fibroemphysematous changes. Of 21 cases that we studied, six (28%) had clinical and/or electrocardiographic features of cor pulmonale. The cause of cor pulmonale often evoked is an invasion of the walls of pulmonary vessels by sarcoid granulomas or their compression by the fibrotic process. Pathological studies in one patient showed compression of large pulmonary arteries associated with specific sarcoid lesions in small small and medium-sized arteries.
Predictors of Relapse in a Prospective Study of Fluoxetine Treatment of Major Depression
Authors: Patrick J. McGrath, Jonathan W. Stewart, Frederic M. Quitkin, Ying Chen, Jonathan E. Alpert, Andrew A. Nierenberg, Maurizio Fava, Jianfeng Cheng, Eva Petkova
Journal: American Journal of Psychiatry (2006)

Objective: Loss of response to a previously effective antidepressant is a common clinical problem. Retrospective analyses have shown that the pattern of response during antidepressant treatment (late onset and persistent versus other patterns) can be used to predict relapse during continuation and maintenance treatment and possibly to identify placebo responses to treatment. This study was designed to test the predictive value of response pattern prospectively and to examine the data for other predictors of relapse. Method: Five hundred seventy persons with major depressive disorder were treated with fluoxetine for 12 weeks and their pattern of response was determined. Those who responded (N=292) underwent random assignment, under double-blind conditions, to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse. Survival analysis was used to examine the effect of covariates on relapse. Results: Although fluoxetine was significantly more effective than placebo during maintenance treatment, this chronically ill group had a high rate of relapse. Contrary to previous findings, a pattern of acute response was not predictive of relapse. Chronicity, symptom severity, a neurovegetative symptom pattern, and female gender were all associated with a significantly greater risk of relapse, with no difference observed between fluoxetine and placebo. Conclusions: The pattern of response to acute treatment appears to be inconsistently predictive of relapse. There is a high rate of relapse with both active medication and placebo in patients with chronic depression. Illness characteristics predict loss of response both to fluoxetine and to placebo. No variable examined was predictive of differential relapse rates between fluoxetine and placebo.
The Continuing Story of Renal Repair with Stem Cells
Authors: Enyu Imai, Hirotsugu Iwatani
Journal: Journal of the American Society of Nephrology (2007)

Renal stem cells are still a hot topic, but their location and mechanism of action continue to elude. The therapeutic potential of intrinsic stem cells to the recovery of damaged kidney has been suggested by a number of recent experiments, whereas the role of various other kinds of administered stem