tbuckley/cabot-search huggingface dataset:
Serum lipoproteins and apolipoproteins in rats with streptozotocin-induced diabetes.
Authors: H Bar-On, P S Roheim, H A Eder
Journal: Journal of Clinical Investigation (1976)

The lipoproteins of rats fed a high sucrose diet and made diabetic by administration of 45 mg/kg of streptozotocin were studied. All lipoprotein classes were found to be present in increased concentrations. The apolipoprotein composition of the various lipoprotein fractions was studied by polyacrylamide-gel electrophoresis in the presence of 8 M urea, isoelectric focusing in the presence of 8 M urea, and sodium dodecyl sulfate gel electrophoresis in polyacrylamide gels. In the very low density lipoproteins (VLDL) of diabetic rats, there was a marked alteration in the relative amounts of C proteins by polyacrylamide-gel electrophoresis, and this was found by isoelectric focusing to be primarily a relative increase in C-III-3 apoprotein and a decrease in C-III-O. In addition, in the diabetic rats, the VLDL contained a protein of mol wt 46,000, the A-IV protein, which normally is only present in the high density lipoproteins. In the high density lipoproteins, (HDL) the same alterations in pattern of the C proteins seen in the VLDL were present. Furthermore, the arginine-rich and A-IV protein normally present in HDL could not be detected in the HDL, although the other apolipoproteins are present. Apolipoprotein concentrations were determined by quantitative immunoelectrophoresis. It was found that in the diabetic rats there was an increase in the total amount of apo-B in the plasma, with the increment divided proportionately between the VLDL and the low density lipoprotein (LDL). The total apo-C concentration of plasma increased minimally. The A-IV concentration of plasma increased by 27%; it decreased markedly in the HDL, but appeared in increased amounts in both VLDL and in the d greater than 1.21 fraction. The arginine-rich protein decreased by 63% in the plasma and decreased significantly in the HDL, but increased in VLDL, LDL, and in the d greater than 1.21 fraction. These alterations in apolipoprotein patterns in diabetic animals suggest that the apolipoproteins may play an important role in determining the concentration of various lipoprotein fractions, or may be the result of altered metabolism of the lipoproteins. These lipoproteins with altered apolipoprotein composition may have important biologic differences from normal lipoporteins. Nevertheless, the HDL, despite the fact that it is deficient in some of its major constituents, was unchanged in its cholesterol content.
Reviewer's reply
Authors: H. G Burger
Journal: BMJ (1996)

EDITOR,—I suggest that the facts be allowed to speak for themselves. Less than one fifth (not half) of my review alluded to “errors and misleading information.” I will deal with each in turn and leave readers to judge to whom such errors are correctly attributable.

Firstly, let me quote from the section of the book dealing with the medical management of hirsutism. “In recent years CPA [[cyproterone acetate]] has been most widely used with a lowdose oestrogen/anti-oestrogen combination containing 35 μg ethinyl oestradiol and 2 mg …
Systemic Delivery of Synthetic MicroRNA-16 Inhibits the Growth of Metastatic Prostate Tumors via Downregulation of Multiple Cell-cycle Genes
Authors: Fumitaka Takeshita, Lubna Patrawala, Mitsuhiko Osaki, Ryou-u Takahashi, Yusuke Yamamoto, Nobuyoshi Kosaka, Masaki Kawamata, Kevin Kelnar, Andreas G. Bader, David Brown, Takahiro Ochiya
Journal: Molecular Therapy (2009)

Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer. Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer.
Pentoxifylline and Diabetic Neuropathy
Authors: KENNETH L. COHEN
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 October 1987Pentoxifylline and Diabetic NeuropathyKENNETH L. COHEN, M.D., SUSANNE HARRIS, PA-CKENNETH L. COHEN, M.D.Search for more papers by this author, SUSANNE HARRIS, PA-CSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-4-600_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The pain and discomfort of diabetic peripheral neuropathy may respond to treatment with pentoxifylline. This drug has the ability to increase erythrocyte flexibility and improve flow in the microvasculature (1). We gave pentoxifylline for 16 weeks to eight patients with type II diabetes with established nephropathy in an attempt to determine whether there would be any beneficial effect on renal function and proteinuria. Although there were no changes in glucose control (fasting blood sugar, and hemoglobin A1C levels) or renal function (blood urea nitrogen, creatinine, or 24-hour urine protein levels), six of seven patients who had painful...References1. SPITTELL J. Pentoxifylline and intermittent claudication. Ann Intern Med. 1985;102:126-7. LinkGoogle Scholar2. NEWRICKFORTGREAVES PIM. Clinicopathological correlates of human diabetic neuropathy [Abstract]. Diabetes. 1987;36(suppl 1):86A. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: West Haven VA Medical Center West Haven, CT 06516 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAre the Protean Effects of Pentoxifylline in the Therapy of Diabetes and Its Complications Still Relevant?Effect of pentoxifylline on diabetic distal polyneuropathy in type 2 diabetic patients: A randomized trialPainful diabetic neuropathyPainful diabetic neuropathyNitric oxide deficiency, leukocyte activation, and resultant ischemia are crucial to the pathogenesis of diabetic retinopathy/ neuropathy — preventive potential of antioxidants, essential fatty acids, chromium, ginkgolides, and pentoxifyllineClinical Update on Pentoxifylline Therapy for Diabetes-Induced Peripheral Vascular DiseaseSkin Blood Flow and Current Perception in Pentoxifylline-Treated Diabetic NeuropathyPentoxifylline in the Treatment of Distal Diabetic Neuropathy 1 October 1987Volume 107, Issue 4Page: 600-601KeywordsGlucoseHemoglobinNeuropathic painNeuropathyPainPeripheral neuropathyProteinsProteinuriaType 2 diabetesUrine Issue Published: 1 October 1987 PDF downloadLoading ...
Timothy Greville Ashworth
Authors: T. Guha
Journal: BMJ (2003)

Consultant histopathologist Walsgrave Hospital, Coventry, 1977-95 (b 1931; q Cape Town 1956; DCP), died from a ruptured dissecting aneurysm of the aorta, causing cardiac tamponade, on 3 September 2002.

He held various posts at the University of Rhodesia and Nyasaland before moving to England in 1977. As consultant histopathologist at Walsgrave Hospital, Coventry, he recognised the virtue of medical laboratory scientific officers performing the “cut up” procedure, thus saving the valuable time of consultant pathologists. After clinical pathology accreditation was denied to Walsgrave because of this practice, he had an article published in the BMJ (1994;309:417) expressing his views on the issue. This caused a furore, but after much debate the Royal College of Pathologists sanctioned a practice that had been considered unthinkable only a few years before. He leaves a wife, three children, and a granddaughter.
Lactic Acidosis Complicating the Acquired Immunodeficiency Syndrome
Authors: Geetinder Chattha
Journal: Annals of Internal Medicine (1993)

Lactic acidosis has been reported in patients with the acquired immunodeficiency syndrome (AIDS) only in association with tissue hypoxia. From 1989 to 1991, seven patients with human immunodeficiency virus (HIV) infection who had lactic acidosis without obvious cause were evaluated. Nine normovolemic patients without acidosis or hypoxia served as controls. Findings in the patients included the following: pH, 7.22 ± 0.07; bicarbonate, 7.0 ± 2.4 mmol/L; and lactate, 14.3 ± 2.6 mmol/L. Patients and controls did not differ regarding cardiac index, PO2, oxygen extraction ratio, and systemic oxygen delivery or utilization. Four patients with AIDS died of overwhelming metabolic acidosis, but the three other patients were discharged from the hospital. Autopsy in the four patients who died showed no obvious cause for lactic acidosis. The normal oxygen delivery, utilization, and extraction suggest that increased hyperlactatemia occurred for reasons other than hypoxia. Thus, patients with AIDS but without hypoxia can develop severe lactic acidosis that is not necessarily fatal.
Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma
Authors: Heinz Ludwig, Hedwig Kasparu, Clemens Leitgeb, Elisabeth Rauch, Werner Linkesch, Niklas Zojer, Richard Greil, Adelheid Seebacher, Ludek Pour, Adalbert Weißmann, Zdeněk Adam
Journal: Blood (2013)
Letter: The UGDP study
Authors: W. M. Hubbard
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The lead editorial in the Feb 10 issue ofThe Journal(231:624, 1975) distorted the careful and scholarly Biometric Society Committee report<sup>1</sup>on its statistical analysis of the University Group Diabetics Program (UGDP)<sup>2</sup>data. The author of the editorial declared, "The probability that oral hypoglycemic agents cause premature deaths from cardiovascular disease remains valid." However, the Committee report found: The possibility that deaths may have been allocated to cardiovascular causes preferentially in the groups receiving oral therapy exists and in view of the "nonsignificance" of differences in total mortality, some reservations about the conclusion that oral hyperglycemics [sic] are toxic must remain. Nonetheless, we consider the evidence of harmfulness moderately strong. The author of the editorial also offered an "estimate that 10,000 to 15,000 such unnecessary deaths occur each year in the United States alone" as a result of these drugs. This statement was the
Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation
Authors: Chiu-Ling Chen, Yen-Wen Tseng, Jaw-Ching Wu, Guan-Yu Chen, Kuan-Chen Lin, Shiaw-Min Hwang, Yu-Chen Hu
Journal: Biomaterials (2015)
Abstract 5563: Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients
Authors: Charlotte Aaberg-Jessen, Stine S. Jensen, Signe L. Nielsen, Christian B. Pedersen, Nils Brünner, Bjarne W. Kristensen
Journal: Cancer Research (2012)

Abstract Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been associated with poor prognosis in various cancers as well as with resistance towards chemotherapy. In a previous study we found an association between a high immunohistochemical TIMP-1 protein level and a shorter survival for glioblastoma patients. The aim of the present study was to further evaluate TIMP-1 as a prognostic marker in gliomas by performing TIMP-1 fluorescence in situ hybridization (FISH) and by measuring TIMP-1 in plasma. TIMP-1 FISH analysis was performed on 33 glioblastoma biopsies in order to elucidate if the increased levels of TIMP-1 protein could be explained by gene amplification. Moreover, blood samples were collected from 43 patients (31 gliomas including 21 glioblastomas) prior to brain tumor surgery. The plasma TIMP-1 protein level was measured by ELISA. The results showed TIMP-1 FISH scores between 0.7 and 1.1, suggesting neither amplification nor loss of the TIMP-1 gene. The TIMP-1 level measured in plasma was not significantly higher than the TIMP-1 level measured in healthy matched controls. No correlation was identified between the immunohistochemical TIMP-1 levels and the FISH scores or the plasma TIMP-1 levels. In conclusion, TIMP-1 FISH scores or plasma TIMP-1 levels are without prognostic potential in gliomas. The present study suggests that the high immunohistochemical TIMP-1 protein levels in gliomas are not caused by TIMP-1 gene amplification. Moreover, TIMP-1 in plasma is low and not directly related to the tumor TIMP-1 level found by immunohistochemistry. The study suggests that TIMP-1 immunohistochemistry is the method of choice when using TIMP-1 as a biomarker in gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5563. doi:1538-7445.AM2012-5563
Sex inequalities in health care need tackling
Authors: Rory Watson
Journal: BMJ (2005)

Pressure is growing on healthcare professionals and pharmaceutical companies to grant greater importance to sex inequalities in public health policies. Swedish Green MEP Eva-Britt Svensson has begun preparing a report on the issue for the European parliament, which she expects to complete in July.

“I want to look at how men and women with the same disease are treated and to establish whether there are differences in the care they receive. Once we have a clear picture we …
PKC-β activation inhibits IL-18-binding protein causing endothelial dysfunction and diabetic atherosclerosis
Authors: Marie-Claude Durpès, Catherine Morin, Judith Paquin-Veillet, Raphaël Beland, Martin Paré, Marie-Odile Guimond, Mark Rekhter, George L King, Pedro Geraldes
Journal: Cardiovascular Research (2015)

Clinical observations showed a correlation between accelerated atherosclerosis in diabetes and high plasmatic level of IL-18, a pro-inflammatory cytokine. IL-18 enhances the production of inflammatory cytokines and cellular adhesion molecules contributing to atherosclerotic plaque formation and instability. Previous studies indicated that protein kinase C (PKC)-β inhibition prevented macrophage-induced cytokine expression involved in diabetic (DM) atherosclerotic plaque development. However, the role of PKC-β activation on IL-18/IL-18-binding protein (IL-18BP) pathway causing endothelial dysfunction and monocyte adhesion in diabetes has never been explored. Apoe−/− mice were rendered DM and fed with western diet containing ruboxistaurin (RBX), a PKC-β inhibitor. After 20 weeks, atherosclerotic plaque composition was quantified. Compared with non-diabetic, DM mice exhibited elevated atherosclerotic plaque formation, cholestoryl ester content and macrophage infiltration, as well as reduced IL-18BP expression in the aorta which was prevented with RBX treatment. Endothelial cells (ECs) and macrophages were exposed to normal or high glucose (HG) levels with or without palmitate and recombinant IL-18 for 24 h. The combined HG and palmitate condition was required to increase IL-18 expression and secretion in macrophages, while it reduced IL-18BP expression in EC causing up-regulation of the vascular cell adhesion molecule (VCAM)-1 and monocyte adhesion. Elevated VCAM-1 expression and monocyte adherence were prevented by siRNA, RBX, and IL-18 neutralizing antibody. Our study unrevealed a new mechanism by which PKC-β activation promotes EC dysfunction caused by the de-regulation of the IL-18/IL-18BP pathway, leading to increased VCAM-1 expression, monocyte/macrophage adhesion, and accelerated atherosclerotic plaque formation in diabetes.
Developing Asthma in Childhood from Exposure to Secondhand Tobacco Smoke: Insights from a Meta-Regression
Authors: Kathleen L. Vork, Rachel L. Broadwin, Robert J. Blaisdell
Journal: Environmental Health Perspectives (2007)

Studies have identified associations between household secondhand tobacco smoke (SHS) exposure and induction of childhood asthma. However, the true nature and strength of this association remains confounded in many studies, producing inconsistent evidence. To look for sources of potential bias and try to uncover consistent patterns of relative risk estimates (RRs), we conducted a meta-analysis of studies published between 1970 and 2005.Through an extensive literature search, we identified 38 epidemiologic studies of SHS exposure and the development of childhood asthma (that also controlled for atopy history) from 300 potentially relevant articles.We observed substantial heterogeneity within initial summary RRs of 1.48 [95% confidence interval (CI), 1.32-1.65], 1.25 (1.21-1.30), and 1.21 (1.08-1.36), for ever, current, and incident asthma, respectively. Lack of control for type of atopy history (familial or child) and child's own smoking status within studies and age category altered summary RRs in separate meta-regressions. After adjusting for these confounding characteristics, consistent patterns of association emerged between SHS exposure and childhood asthma induction. Our summary RR of 1.33 (95% CI, 1.14-1.56) from studies of incident asthma among older children (6-18 years of age) is 1.27 times the estimate from studies of younger children and higher than estimates reported in earlier meta-analyses.This new finding indicates that exposure duration may be a more important factor in the induction of asthma than previously understood, and suggests that SHS could be a more fundamental and widespread cause of childhood asthma than some previous meta-analyses have indicated.
Peninsular derring do
Authors: W. Moore
Journal: BMJ (2009)

The dangers and deprivations of battlefield surgery will always demand seemingly superhuman feats of courage. Yet the sheer derring do of the early 19th century army surgeon George Guthrie (1785-1856) seems culled straight from the pages of a Boy’s Own story.

Apprenticed to a surgeon at the tender age of 13, Guthrie passed his College of Surgeons examination at 15 and, having lied about his age, promptly enrolled as a surgical assistant in the British army bound for Canada. Returning home in 1807, Guthrie averted disaster when he spied the English coast fast approaching and single handedly piloted the ship to safety.

The following year he landed in Portugal with British troops, under the command of the …
Leptinemia Is Not a Risk Factor for Ischemic Heart Disease in Men: Prospective results from the Quebec Cardiovascular Study
Authors: Charles Couillard, Benoît Lamarche, Pascale Mauriège, Bernard Cantin, Gilles R Dagenais, Sital Moorjani, Paul-J Lupien, Jean-Pierre Després
Journal: Diabetes Care (1998)

OBJECTIVE To investigate the possibility that leptin levels may be predictive of the risk of ischemic heart disease (IHD) through the relationship of leptin to body fat. RESEARCH DESIGN AND METHODS The Quebec Cardiovascular Study cohort consisted of 2,103 French-Canadian men without IHD in 1985 who were followed until 1990, by which time 114 had experienced an IHD event. These 114 men were then individually matched for age, BM1, cigarette smoking, and alcohol intake with 114 subjects who were free of IHD at follow-up. After exclusion of diabetic patients and those in whom leptin levels could not be measured, we were able to compare the initial metabolic profiles of 86 men in the IHD group and of 95 control subjects. RESULTS Plasma leptin concentrations were positively correlated with BMI (r = 0.67, P &amp;lt; 0.0001) and with fasting insulin concentrations (r = 0.46, P &amp;lt; 0.0001) in the overall sample. These significant associations were also observed when men with IHD and the control subjects were examined separately (control subjects: r = 0.68 for BMI and r = 0.45 for insulin; IHD subjects: r = 0.65 for BMI and r = 0.50 for insulin). With the exception of plasma triglyceride (r = 0.25, P &amp;lt; 0.001), no significant association was found between leptin and plasma lipoprotein and lipid concentrations. Furthermore, plasma insulin remained significantly associated with leptin levels even after adjustment for BMI (r = 0.22, P &amp;lt; 0.005). There was no difference in baseline leptin levels among men who developed IHD versus men who remained IHD-free during the 5-year follow-up (5.56 ± 3.12 vs. 5.36 ± 2.90 ng/ml, respectively). Thus, although significantly correlated with the BMI and fasting insulin levels, plasma leptin concentration was not a significant predictor of the 5-year incidence of IHD. This lack of a relationship to IHD was noted when leptin levels were analyzed as tertiles and when leptin concentration was analyzed as a continuous variable. CONCLUSIONS These prospective results suggest that leptinemia, despite being a strong correlate of obesity, does not appear to be an independent risk factor for the development of IHD in men.
The AMA and US Health Policy Since 1940
Authors: Tom E. Nesbitt
Journal: JAMA (1985)

Neither the definition nor the development of "policy" is clearly understood by many people. John Alexander McMahon, president of the American Hospital Association, was once asked what constituted policy. His response: "anything that's important." Campion's grasp of the critical elements and the evolutionary process from which policy positions emerge gives the reader a fascinating trip through America's complex medical system. Using the American Medical Association (AMA) as a focal point for orientation, Campion initially introduces the reader to medicine and the AMA at the turn of the century with a review of the existing social, economic, and political forces surrounding medicine. With sufficient attention given to each of these forces, the gigantic strides made by American medicine are more readily understood. The advances in the public health environment, coupled with scientific and technological achievements, provide the backdrop for Campion's depiction of policy development as it is intertwined with societal needs.