tbuckley/cabot-search huggingface dataset:
Pre-race drop-out in marathon runners: reasons for withdrawal and future plans.
Authors: P J Clough, S Dutch, R J Maughan, J Shepherd
Journal: British Journal of Sports Medicine (1987)

This study examines the reasons given for non-participation in the 1984 Aberdeen Milk Marathon by those people who entered for the race but did not run. The major reason was found to be injury during training. The future running plans of the sample were also investigated and it was found that the vast majority aimed to continue marathon running. Around two-thirds of the sample had decided not to run at least two weeks before the day of the race. A third of the respondents indicated that they would have taken part in the race had there been a half marathon option.
Evolution of a case of lung plasma cell granuloma
Authors: JE Gonzalez-Moya, J Hueto, AY Ruiz de Azua, J Sanchez, T Franquet
Journal: European Respiratory Journal (1991)

Plasma cell granuloma, on lung inflammatory pseudotumour, is a localized benign proliferation of plasma cells and mesenchymal cells. We report the case of a 45 yr old male, who first presented with mild pain in the left side of the chest. Chest radiography was normal. Eight weeks later he had more pain and an opacity in the left and lower zones of his left chest. After another 7 weeks he had fever and cough with yellowish-green sputum. Chest X-ray then showed a round density in the left upper lobe. The final diagnosis was established after thoracotomy histological examination.
Statin inhibits hypoxia-induced endothelin-1 via accelerated degradation of HIF-1α in vascular smooth muscle cells
Authors: Tetsuya Hisada, Makoto Ayaori, Nobuhiro Ohrui, Hiroshi Nakashima, Kazuhiro Nakaya, Harumi Uto-Kondo, Emi Yakushiji, Shunichi Takiguchi, Yoshio Terao, Yoshinori Miyamoto, Takeshi Adachi, Haruo Nakamura, Fumitaka Ohsuzu, Katsunori Ikewaki, Yutaka Sakurai
Journal: Cardiovascular Research (2012)

Endothelin-1 (ET-1) contributes to the pathogenesis of cardiovascular diseases with multiple properties such as vasoconstriction. Human ET-1 gene expression is up-regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1) through hypoxia response element (HRE). Although previous studies suggested that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) alter HIF-1-related gene expression, it remained unclear whether statins modulate HIF-1-mediated ET-1 expression. Therefore, we investigated the effect of fluvastatin on hypoxia-induced human ET-1 expression in vascular smooth muscle cells (VSMC).Hypoxia (1% O(2)), compared with the normoxic condition (21% O(2)), significantly induced the expression of preproET-1 mRNA, ET-1 protein, and ET-1 secretion in VSMC. Hypoxia induced a 2.3-fold increase in HRE-dependent ET-1 reporter gene activation. Under concentrations of 1 µmol/L or greater, fluvastatin attenuated the hypoxia-induced ET-1 gene expression through the accelerated ubiquitin/proteasome-dependent degradation of HIF-1α, thus consequently attenuating HIF-1α binding to the HRE of the ET-1 gene. These inhibitory effects of fluvastatin were cancelled by concomitant treatment with mevalonate, farnesyl pyrophosphate, or geranylgeranyl pyrophosphate, but not squalene.The present study suggests that fluvastatin attenuates HIF-1-dependent ET-1 gene expression in conjunction with the stimulation of HIF-1α ubiquitin/proteasome-dependent degradation via isoprenoid-dependent mechanisms.
A case of emphysematous pyelonephritis
Authors: Thomas Clark, Mei Abdalkareem, Khalid Ali
Journal: Journal of the Royal Society of Medicine (2009)

Emphysematous pyelonephritis (EPN) is a rare but life-threatening, fulminant, necrotizing infection of the renal and perirenal tissues that is characterized by gas formation. In this case a 34-year-old woman with poorly controlled diabetes presented with symptoms indicative of a severe pyelonephritis. Following a failed response to initial treatment measures, a diagnosis of EPN was made following a CT scan. With aggressive fluid resuscitation, antibiotics and decompression with nephrostomy, the patient improved and avoided surgical intervention. The diagnosis, classification and treatment of EPN are discussed.
New Insights into Nephrogenic Systemic Fibrosis
Authors: Sundararaman Swaminathan, Sudhir V. Shah
Journal: Journal of the American Society of Nephrology (2007)

Nephrogenic systemic fibrosis is a new disorder reported almost exclusively in patients who have renal insufficiency and are exposed to contrast media formulated with gadolinium. High morbidity and mortality are associated with this severely disabling and painful condition. The acute phase begins upon exposure to gadolinium contrast media, characterized by a systemic inflammatory response involving iron mobilization, and then as a progressive, chronic phase in which fibrosis develops. Proposed is a unifying model of cumulative risk factors in which the interplay of systemic inflammation and stimulated hematopoietic environment associated with hyperparathyroidism and erythropoietin may tie to a common pathogenic mechanism of fibrogenesis. Because there are no uniformly effective interventions to treat nephrogenic systemic fibrosis other than successful renal transplantation, prevention by avoiding gadolinium contrast media in patients with chronic kidney disease is vital. On the basis of suspected pathogenesis, it is also reasonable to limit erythropoietin and iron therapy to dosages ensuring recommended targets and adequately control hyperparathyroidism. Herein is reviewed what is currently known about this subject.
Somatic mutation of human immunoglobulin V genes in the X-linked HyperIgM syndrome.
Authors: Y W Chu, E Marin, R Fuleihan, N Ramesh, F S Rosen, R S Geha, R A Insel
Journal: Journal of Clinical Investigation (1995)

Somatic mutation of Ig variable regions occurs prominently in germinal centers, but it has been debated whether the mutation process initiates in germinal centers or is activated before germinal center entry of B cells. We have analyzed for the presence of somatic mutation in Ig gene rearrangements of the nonpolymorphic human VH6 gene in the X-linked HyperIgM syndrome, which is associated with defective CD40 ligand expression and absence of germinal centers and generation of memory B lymphocytes. IgM and rare IgG VH6 productive rearrangements were isolated from PBL of patients with X-linked HyperIgM syndrome. Although the majority of both the IgM and IgG VH6 rearrangements had a germline VH6 sequence, 7 of 102 VH6 IgM and 1 of 6 IgG rearrangements had a mutated VH6 gene. The mutation frequency (mutations/bp) was 1.4% with a range of 2-9 mutations per clone, a mutation frequency lower, however, than that observed in IgM (3.2%) and IgG (5.4%) VH6 rearrangements of normal individuals. These results suggest that somatic mutation may be initiated in a CD40 ligand-independent pathway before entry of B cells into germinal centers, but fails to achieve the high mutation frequency observed in the presence of germinal centers.
Microchimerism and Autoimmune Disease
Authors: J. Lee Nelson
Journal: New England Journal of Medicine (1998)

The mythological Chimera is described as having the head of a lion, the body of a goat, and the tail of a serpent. In medicine, the term “chimera” is used to indicate a body that contains cell populations derived from different individuals. To pioneers in the development of tests of maternal peripheral blood for prenatal diagnosis, persistent low levels of chimerism (microchimerism) with fetal cells from an earlier pregnancy was an impediment to accurate diagnosis. This impediment was cast in a different light by studies of peripheral blood from normal women who had previously given birth; male DNA was identified . . .
Primary Tumor Hypoxia Recruits CD11b+/Ly6Cmed/Ly6G+ Immune Suppressor Cells and Compromises NK Cell Cytotoxicity in the Premetastatic Niche
Authors: Jaclyn Sceneay, Melvyn T. Chow, Anna Chen, Heloise M. Halse, Christina S.F. Wong, Daniel M. Andrews, Erica K. Sloan, Belinda S. Parker, David D. Bowtell, Mark J. Smyth, Andreas Möller
Journal: Cancer Research (2012)

Abstract Hypoxia within a tumor acts as a strong selective pressure that promotes angiogenesis, invasion, and metastatic spread. In this study, we used immune competent bone marrow chimeric mice and syngeneic orthotopic mammary cancer models to show that hypoxia in the primary tumor promotes premetastatic niche formation in secondary organs. Injection of mice with cell-free conditioned medium derived from hypoxic mammary tumor cells resulted in increased bone marrow–derived cell infiltration into the lung in the absence of a primary tumor and led to increased metastatic burden in mammary and melanoma experimental metastasis models. By characterizing the composition of infiltrating bone marrow–derived cells, we identified CD11b+/Ly6Cmed/Ly6G+ myeloid and CD3−/NK1.1+ immune cell lineages as key constituents of the premetastatic niche. Furthermore, the cytotoxicity of natural killer (NK) cells was significantly decreased, resulting in a reduced antitumor response that allowed metastasis formation in secondary organs to a similar extent as ablation of NK cells. In contrast, metastatic burden was decreased when active NK cells were present in premetastatic lungs. Together, our findings suggest that primary tumor hypoxia provides cytokines and growth factors capable of creating a premetastatic niche through recruitment of CD11b+/Ly6Cmed/Ly6G+ myeloid cells and a reduction in the cytotoxic effector functions of NK cell populations. Cancer Res; 72(16); 3906–11. ©2012 AACR.
Safety and Tolerability of Pravastatin in Long-Term Clinical Trials
Authors: Marc A. Pfeffer, Anthony Keech, Frank M. Sacks, Stuart M. Cobbe, Andrew Tonkin, Robert P. Byington, Barry R. Davis, Carola P. Friedman, Eugene Braunwald
Journal: Circulation (2002)

Background — Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data. Clinical trials designed to assess efficacy are often insufficiently powered to generate reliable safety data. Methods and Results — The West of Scotland Coronary Prevention Study (WOSCOPS), the Cholesterol and Recurrent Events (CARE), and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) studies collectively accumulated &gt;112 000 person-years of exposure in double-blind randomized trials comparing placebo and pravastatin (40 mg once daily). During 5 years of exposure, the incidence of fatal and nonfatal cancers was similar between pravastatin and placebo groups. No differences in noncardiovascular serious adverse events were detected. With &gt;243 000 blood sample analyses, the percentage of patients with any abnormal liver function test after baseline sampling was similar (&gt;3× the upper limit of normal for alanine aminotransferase: 128 [1.4%] versus 131 [1.4%] patients for pravastatin versus placebo, respectively). Study medication was withdrawn in 3 pravastatin and 7 placebo patients due to creatine phosphokinase elevations; no cases of mild or severe myopathy were reported. A Cox regression model considering treatment group, age, diabetes, smoking, whether primary or secondary prevention study, and cardiovascular serious adverse events indicates that the likelihood of discontinuing pravastatin was less than placebo. Conclusions — This prospective analysis indicates that during prolonged exposure, 40 mg of pravastatin is well tolerated, with no excess of noncardiovascular serious adverse events, including liver function abnormalities and laboratory and clinical evidence for myositis. These extensive safety and tolerability data provide important information for therapeutic decisions regarding this pharmacological agent.
STUDIES ON BACTERIEMIA
Authors: David E. Rogers, Marian Ann Melly
Journal: The Journal of Experimental Medicine (1957)

Large numbers of E. coli were rapidly removed from the blood stream of rabbits at rates which initially paralleled the removal of similar numbers of staphylococci. Splanchnic tissues removed approximately two-thirds of the circulating bacilli in transit through the liver and spleen. In contrast to the cessation of splanchnic trapping noted 20 to 40 minutes following the injection of staphylococci, splanchnic trapping of E. coli continued unchanged for 3 to 5 hours unless the splanchnic tissues were dearly reseeding the blood stream. This resulted in the continued disappearance of E. coli over a 60 to 90 minute period, and differed from the constant bacteriemia maintained beyond 20 minutes after the injection of staphylococci. Some of the differences in the initial clearance of these two microorganisms appeared to relate to differences in host leukocyte-bacterium relationships. In vitro studies indicated that E. coli were rapidly killed following ingestion by rabbit polymorphonuclear leukocytes. Staphylococci survive such ingestion. The injection of E. coli was followed by a prolonged granulocytopenia with evidence of sequestration of granulocytes within the pulmonary vascular bed. The injection of staphylococci was followed by a transient leukopenia, with rapid return of granulocytes to the circulation (15). It appears probable that E. coli ingested by sequestered leukocytes are destroyed within the cell, and that leukocytes do not reenter the circulation containing living E. coli. Such intraleukocytic residence in the blood stream has been shown to be of possible importance in the maintenance of staphylococcal bacteriemia (14). An increasing E. coli bacteriemia occurred rapidly after the initial clearance period, indicating that many sequestered bacilli remained viable. Increasing bacteriemia also occurs 3 to 5 hours after the injection of staphylococci. The bacterial or host cell mechanisms which allow this secondary resurgence of bacterial populations are currently under investigation.
Does mechanical stretching have a role in the causation of breast leiomyomas?
Authors: G.N. Prasad, B.D. Radotra, B. Kumar
Journal: British Journal of Dermatology (2004)

Sir, Pilar cutaneous leiomyomas, which arise from the arrectores pilorum muscles, are the second most common benign smooth muscle neoplasms in the body.1 They are most common on the extensor aspects of the limbs, followed by the trunk, face and neck.2–4 Great variation in patient age and sex and anatomical distribution of leiomyomas has been reported in previous studies.2–4 We have retrospectively analysed the case records of patients with cutaneous pilar leiomyomas seen at our clinic during the last 15 years, to evaluate their clinical and histopathological features. Of a total of 16 450 skin biopsies taken over this period, there were 26 histopathologically confirmed cases of leiomyoma cutis. The overall incidence was 0·16% (one leiomyoma cutis for every 632·7 skin biopsies). Of the 26 cases, 18 (69%) occurred in females and eight (31%) in males, giving a female to male sex ratio of 2·25 : 1. The duration of lesions at the time of presentation ranged from 3 months to 10 years (mean ± SD 2·9 ± 2·2 years). Concerning anatomical distribution, 17 (65%) patients had lesions over the trunk, seven (27%) on the extremities and two (8%) at multiple sites (trunk and upper extremities) in a zosteriform distribution. To our surprise, among the 17 patients with lesions over the trunk, 14 were women, all of whom had lesions over the breasts. Of these 14 women, eight had a single lesion (on the right breast in five and on the left breast in three). Of the remaining six women who had multiple lesions, four showed a bilateral distribution (Fig. 1a) and one each had more than one lesion over the right or left breast (Fig. 1b). All the lesions were predominantly present over the upper quadrants of the breasts. All the women with lesions over the breasts were obese, having voluminous, pendulous breasts. Morphologically, the lesions ranged from skin‐coloured to reddish‐brown papules, nodules and plaques varying in size from 0·5 to 5 cm. Lesions were tender in 10 patients. A family history of leiomyoma cutis was negative in all the patients, and none had associated systemic manifestations. One patient had recurrence within a month after excision.
Mechanisms by which angiotensin II affects the heart rate of the conscious sheep.
Authors: W B Lee, M J Ismay, E R Lumbers
Journal: Circulation Research (1980)

Intravenous infusions of angiotensin II were given to conscious sheep. During these infusions, the pressor action of angiotensin was antagonized by concomitant infusion of sodium nitroprusside. Under these conditions, angiotensin produced a dose-dependent tachycardia. This dose-dependent tachycardia was not affected by propranolol and therefore it was not due to an action of angiotensin on sympathoadrenal mechanisms. The dose-dependent tachycardia was reduced by atropine, and abolished by increases in systolic pressure. We conclude that iv infusions of angiotensin cause a central, dose-dependent reduction in vagal tone. This action is normally antagonized by the baroreceptor reflex response to the hypertensive action of angiotensin. Therefore, in those conditions in which endogenous angiotensin production is increased and blood pressure is not elevated (e.g., sodium deficiency and pregnancy), angiotensin may influence heart rate.
Phase I, dose-finding study of capecitabine in combination with docetaxel and epirubicin as first-line chemotherapy for advanced breast cancer
Authors: M. Venturini, L. Del Mastro, O. Garrone, C. Angiolini, M. Merlano, M. Bergaglio, G. Tolino, A. Lambiase, A. Baldini, G. Canavese, R. Rosso
Journal: Annals of Oncology (2002)
Development of a Syngeneic Rat Brain Tumor Model Expressing EGFRvIII and Its Use for Molecular Targeting Studies with Monoclonal Antibody L8A4
Authors: Weilian Yang, Rolf F. Barth, Gong Wu, Michael J. Ciesielski, Robert A. Fenstermaker, Bradford A. Moffat, Brian D. Ross, Carol J. Wikstrand
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The goals of the present study were 2-fold: (a) to develop and characterize a rat brain tumor model that could be used for studies of molecular targeting of EGFRvIII and (b) to study the tumor localizing properties of radiolabeled monoclonal antibody (mAb) L8A4, specifically directed against EGFRvIII, following systemic, i.t., and convection enhanced delivery to brain tumor–bearing rats. Experimental Design and Results: F98 wild-type (F98WT) rat glioma cells were transfected with a gene encoding human EGFRvIII, and following selection and cloning, a cell line, designated F98npEGFRvIII, was identified, which expressed a nonconstitutively phosphorylated form of the receptor. As determined by a radioligand binding assay, there were 1.2×105 EGFRvIII sites per cell compared with an undetectable number on F98WT cells. The tumorigenicity of the F98npEGFRvIIIglioma was studied following i.c. implantation of 103, 104, or 105 cells into CD-Fischer rats. Mean survival times were 23, 17, and 13 days, respectively, which were equivalent to those obtained with F98EGFR and F98WT cells. As determined by magnetic resonance imaging, the mean doubling times for the F98WT and F98npEGFRvIII gliomas were similar (59.8 ± 4.8 versus 52 ± 3.3 hours). Following i.v. administration to glioma-bearing rats, mAb L8A4 specifically targeted the F98npEGFRvIII glioma, and at 24 hours, 7.7% of the injected dose per gram (ID/g) localized in the tumor. This increased 5-fold to 39.5% ID/g following i.t. injection and 7-fold to 59.8% ID/g at 24 hours following convection enhanced delivery. Conclusions: Based on these data, we have concluded that the F98npEGFRvIII glioma should be a valuable animal model for therapy studies focusing on molecular targeting of EGFRvIII by receptor specific mAbs.
The Fibroblast Growth Factor Receptor-4 Arg388 Allele Is Associated with Prostate Cancer Initiation and Progression
Authors: Jianghua Wang, David W. Stockton, Michael Ittmann
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Increased expression of fibroblast growth factors that can activate the fibroblast growth factor receptor-4 (FGFR-4) occurs in a substantial fraction of human prostate cancers in vivo. A germline polymorphism of the FGFR-4 gene resulting in expression of arginine at codon 388 (Arg388) is associated with aggressive disease in patients with breast and colon cancer. We therefore sought to determine whether the FGFR-4 Arg388 allele was associated with prostate cancer incidence and/or the occurrence of aggressive disease. Experimental Design: The FGFR-4 genotype of men undergoing radical prostatectomy and controls of the same race was determined and the genotype correlated with clinical and pathologic markers of disease aggressiveness. PNT1A cell lines expressing predominantly the FGFR-4 Arg388 or Gly388 allele were established, and cell migration and invasiveness of these cells were assessed by a wounding assay and by quantitative determination of invasion through Matrigel. Expression of urokinase-type plasminogen activator receptor was determined by quantitative RT-PCR and enzyme-linked immunoabsorption assay. Results: Homozygosity for the FGFR-4 Arg388 allele is strongly associated with the occurrence of prostate cancer in white men. The presence of the FGFR-4 Arg388 allele is also correlated with the occurrence of pelvic lymph node metastasis and biochemical (prostate-specific antigen) recurrence. Expression of FGFR-4 Arg388 in immortalized prostatic epithelial cells results in increased cell motility and invasion through Matrigel and was associated with increased expression of urokinase-type plasminogen activator receptor. Conclusion: The FGFR-4 Arg388 allele is associated with both an increased incidence and clinical aggressiveness of prostate cancer and results in changes in cellular motility and invasiveness in immortalized prostate epithelial cells consistent with the promotion of metastasis.
HDL Cholesterol Is Not Associated with Lower Mortality in Patients with Kidney Dysfunction
Authors: Stephen Zewinger, Thimoteus Speer, Marcus E. Kleber, Hubert Scharnagl, Rainer Woitas, Philipp M. Lepper, Karolin Pfahler, Sarah Seiler, Gunnar H. Heine, Winfried März, Günther Silbernagel, Danilo Fliser
Journal: Journal of the American Society of Nephrology (2014)

In the general population, HDL cholesterol (HDL-C) is associated with reduced cardiovascular events. However, recent experimental data suggest that the vascular effects of HDL can be heterogeneous. We examined the association of HDL-C with all-cause and cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health study comprising 3307 patients undergoing coronary angiography. Patients were followed for a median of 9.9 years. Estimated GFR (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine-cystatin C (eGFRcreat-cys) equation. The effect of increasing HDL-C serum levels was assessed using Cox proportional hazard models. In participants with normal kidney function (eGFR>90 ml/min per 1.73 m(2)), higher HDL-C was associated with reduced risk of all-cause and cardiovascular mortality and coronary artery disease severity (hazard ratio [HR], 0.51, 95% confidence interval [95% CI], 0.26-0.92 [P=0.03]; HR, 0.30, 95% CI, 0.13-0.73 [P=0.01]). Conversely, in patients with mild (eGFR=60-89 ml/min per 1.73 m(2)) and more advanced reduced kidney function (eGFR<60 ml/min per 1.73 m(2)), higher HDL-C did not associate with lower risk for mortality (eGFR=60-89 ml/min per 1.73 m(2): HR, 0.68, 95% CI, 0.45-1.04 [P=0.07]; HR, 0.84, 95% CI, 0.50-1.40 [P=0.50]; eGFR<60 ml/min per 1.73 m(2): HR, 1.18, 95% CI, 0.60-1.81 [P=0.88]; HR, 0.82, 95% CI, 0.40-1.69 [P=0.60]). Moreover, Cox regression analyses revealed interaction between HDL-C and eGFR in predicting all-cause and cardiovascular mortality (P=0.04 and P=0.02, respectively). We confirmed a lack of association between higher HDL-C and lower mortality in an independent cohort of patients with definite CKD (P=0.63). In summary, higher HDL-C levels did not associate with reduced mortality risk and coronary artery disease severity in patients with reduced kidney function. Indeed, abnormal HDL function might confound the outcome of HDL-targeted therapies in these patients.