tbuckley/cabot-search huggingface dataset:
Contribution of Nonproteolytically Activated Prorenin in Glomeruli to Hypertensive Renal Damage
Authors: Atsuhiro Ichihara, Yuki Kaneshiro, Tomoko Takemitsu, Mariyo Sakoda, Tsutomu Nakagawa, Akira Nishiyama, Hiroshi Kawachi, Fujio Shimizu, Tadashi Inagami
Journal: Journal of the American Society of Nephrology (2006)

Prorenin is activated without proteolysis by binding of prorenin receptor to the pentameric "handle region" (HR) of prorenin prosegment. It was hypothesized that such activation occurs in the kidneys of hypertensive rats and causes tissue renin-angiotensin system (RAS) activation and end-organ damage. Because the HR's binding to its binding protein made the adjacent tetrameric "gate region" (GR) accessible to its specific antibody, immunohistochemistry of the GR was performed to test the hypothesis. Methods also were devised specifically to inhibit the nonproteolytic activation by the decapeptide corresponding to the HR as a decoy. Immunohistochemistry of the GR demonstrated that the majority of nonproteolytically activated prorenin is present in podocytes of the kidneys from stroke-prone spontaneously hypertensive rats, in which activation of renal tissue RAS, proteinuria, and glomerulosclerosis occurred. Continuous subcutaneous administration of the HR decoy peptide completely inhibited both nonproteolytic activation of tissue prorenin and activation of tissue RAS without affecting circulating RAS or arterial pressure and significantly attenuated the development and progression of proteinuria and glomerulosclerosis. These studies clearly demonstrated that nonproteolytic activation of prorenin in glomeruli is critically involved in renal tissue RAS activation, leading to renal damage in hypertensive animals.
Increased vulnerability of postarthritic cartilage to a second arthritic insult: accelerated MMP activity in a flare up of arthritis
Authors: J B van Meurs, P L van Lent, A A van de Loo, A E Holthuysen, E K Bayne, I I Singer, W B van den Berg
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Murine antigen induced arthritis (AIA) is a chronic, smouldering inflammation. Flares of arthritis can be induced by antigen rechallenge or exposure to inflammatory mediators like interleukin 1 (IL1). These flares are characterised by a fast and marked proteoglycan (PG) depletion if compared with the initial arthritis. This study investigated the involvement of metalloproteinases in both the initial and the flare phase of arthritis. <h3>METHODS</h3> Murine AIA was induced and a flare up of arthritis was induced by injection of 10 ng of IL1β. Messenger RNA levels of MMP-1 and -3 were studied by RT-PCR. MMP activity in cartilage, during both primary AIA as well as the flare up of arthritis, was studied by immunodetection of MMP specific neoepitopes in aggrecan (VDIPEN). Cartilage just before flare induction was analysed for presence of MMPs at the mRNA level as well as at the protein level by zymography. <h3>RESULTS</h3> At the onset of AIA, a fast upregulation of mRNA for stromelysin and collagenase was noted. However, no VDIPEN epitopes were detected during this early phase of arthritis. They appeared when PG depletion was severe at day 7 of arthritis and disappeared when cartilage was repaired. IL1 injection into a knee joint at week 4 of AIA caused a flare up of arthritis, coinciding with a fast and marked PG degradation. This degradation was characterised by accelerated expression of VDIPEN epitopes if compared with the expression in primary AIA. Analysis of cartilage at week 4 of AIA showed still increased mRNA levels of MMP-1 and -3. Moreover, increased levels of latent MMPs were present as well, as APMA activation induced profound VDIPEN epitope. In vitro exposure to IL1 did show increased PG breakdown but no VDIPEN expression, suggesting that factors in addition to IL1 are needed to cause the in vivo VDIPEN expression. <h3>CONCLUSIONS</h3> The fast and marked PG depletion seen in a flare up of AIA coincides with accelarated expression of MMP induced neoepitopes compared with expression during primary AIA. This accelerated expression is probably linked to increased levels of latent enzyme, which were found to be present in the cartilage before induction of a flare up.
Obesity, Hypertension, and Insulin Resistance
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2002)

This article summarizes material presented at the meeting of the American Society of Hypertension (ASH) in New York, New York, May, 2002, as well as presentations at the American Diabetes Association (ADA) Annual Meeting in San Francisco, California, June, 2002. At a symposium addressing the relationships between obesity, hypertension, and cardiovascular disease at the ASH, Roger Unger (Dallas, TX) discussed lipotoxicity and the metabolic syndrome. He pointed out that over that past 50 years there has been a great change in the food environment, so that the “mechanism for preloading calories, storing them for when a famine occurred,” has led to “hypertrophy and hyperplasia of those adipocytes […]. Famines were eliminated and replaced by a never-ending stream of high-quantity, high-fat, high-carbohydrate foods at the same time that physical exertion dropped to an all-time low.” This has led to a progressive increase in obesity, particularly over the past two decades. “As long as the excess fat remains in the adipocyte,” he stated, “health is not deleteriously affected,” but an “increase in ectopic deposition of lipids” causes the insulin-resistant state, with insulin resistance per se characterized by Unger as “not the proximal cause of the syndrome.” Unger examined monogenic disorders of lack of leptin action to understand “the mechanism of the disorder.” These syndromes, which lead to components of the metabolic syndrome, suggest that leptin resistance or deficiency may be a more central cause than insulin resistance.

The normal actions of leptin can be seen in animal models of obesity, with overfeeding leading to hyperleptinemia, which may cause fat to deposit primarily in the adipocyte. Normal islets, as an example, “fill up with triglycerides” when incubated with fatty acids, but this can be prevented by administration of leptin. When leptin action is insufficient, as seen in the fatty/fatty ( fa/fa ) rat with loss-of-function …
Hazardous Waste Disposal: Emerging Technologies and Public Policies to Reduce Public Health Risks
Authors: R. H. Harris, C. W. English, J. H. Highland
Journal: Annual Review of Public Health (1985)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of ...Read More
Effects of octreotide on postprandial systemic and hepatic hemodynamics in patients with postnecrotic cirrhosis
Authors: Han-Chieh Lin, Yang-Te Tsai, Cheng-Chun Huang, Hong-Chiang Meng, Fa-Yauh Lee, Sun-Sang Wang, Shou-Dong Lee, Kwang-Juei Lo
Journal: Journal of Hepatology (1994)
SHP1 Phosphatase-Dependent T Cell Inhibition by CEACAM1 Adhesion Molecule Isoforms
Authors: Takashi Nagaishi, Lily Pao, Sue-Hwa Lin, Hideki Iijima, Arthur Kaser, Shuo-Wang Qiao, Zhangguo Chen, Jonathan Glickman, Sonia M. Najjar, Atsushi Nakajima, Benjamin G. Neel, Richard S. Blumberg
Journal: Immunity (2006)
Angiogenesis and Neoplastic Progression In Vitro&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Ziche, P M Gullino
Journal: JNCI Journal of the National Cancer Institute (1982)

In vivo cell populations at high risk of neoplastic transformation have been shown to acquire the ability to induce new formation of vessels. The present experiments tested whether the same change occurred during neoplastic transformation in vitro. In four cell populations (human HBL 100 mammary epithelium, BALB/c fibroblasts, C57BL-MG epithelium, and Syrian golden hamster embryo cells), angiogenic capacity appeared during their cultivation in vitro and was evident long before a neoplastic transformation could be recognized. The data were interpreted to support the hypothesis that acquisition of angiogenic capacity by a cell population normally devoid of this capacity indicates an increased risk of neoplastic transformation.
International Breast Cancer Study Group Trial of Sentinel Node Biopsy
Authors: Viviana Galimberti
Journal: Journal of Clinical Oncology (2005)

HAART). 5,6As such, HHV-8 viremia is considered a useful marker for monitoring HIV-infected patients with MCD or KS.However, only few data are available for PEL.In our article published in the July 1, 2005, issue of the Journal of Clinical Oncology, 2 of 28 HIV-infected patients with PEL, plasma samples collected at the time of PEL diagnosis were available in 21 cases (75%).The HHV-8 DNA load was determined on DNA preparations from 200 L of plasma, using quantitative real-time PCR (Taqman) assay targeted to ORF26 (using the ABI PRISM 7500 Sequence Detection System; Perkin-Elmer, Wellesley, MA), as described by Oksenhendler et al. 3 As shown in Table 1, the plasma HHV-8 DNA load ranged from undetectable to 754,373 copies/mL.HHV-8 plasma viremia was undetectable in four patients, all of whom were being treated with HAART.Among the 17 patients with detectable plasma HHV-8 DNA levels, the median value was 2,576 copies/mL.In univariate analysis, no statistically significant association was found between a plasma HHV-8 DNA load of more than 40,000 copies/mL and a shorter survival (P ϭ .73;hazard ratio (HR) 1.23; 95% CI, 0.38 to 3.96).Similarly, using a cutoff value of 2,500 copies/mL, close to the median value, we failed to demonstrate any prognostic influence of plasma HHV-8 viral load on survival (P ϭ .87;HR 1.1; 95%CI, 0.38 to 3.24).Many factors are thought to influence the HHV-8 plasma DNA load in HIV-infected patients with PEL, especially the simultaneous presence of KS and/or MCD, the use of HAART or antiherpesvirus drugs, as well as the immunologic status of the patients.In addition, a great variability in the plasma HHV-8 DNA levels might be observed between individuals, according to the type of HHV-8-related disease.As pointed out by Simonelli et al, mul-ticentric cooperative studies are required to solve problems related to sample size.
NATIONAL ECONOMIC INDICES AND REIMBURSEMENT SYSTEMS DETERMINE TRANSCATHETER AORTIC VALVE IMPLANTATION USE IN WESTERN EUROPE
Authors: Darren Mylotte, Stephan Windeker, Ruben Osnabrugge, Thierry Lefèvre, Peter de Jaegere, Christoph Kaiser, Peter Wenaweser, Francesco Maisano, Neil Moat, Lars Søndergaard, Johan Bosmans, Miguel Sousa Uva, Giuseppe Martucci, Ganesh Manoharan, Manel Sabaté, Nicholas van Mieghem, Pieter Kappetein, Patrick Serruys, Ruediger Lange, Nicolo Piazza
Journal: Journal of the American College of Cardiology (2013)
Pathological and physiological functions of presenilins
Authors: Kulandaivelu S Vetrivel, Yun-wu Zhang, Huaxi Xu, Gopal Thinakaran
Journal: Molecular Neurodegeneration (2006)

Mutations in PSEN1 and PSEN2 genes account for the majority of cases of early-onset familial Alzheimer disease. Since the first prediction of a genetic link between PSEN1 and PSEN2 with Alzheimer's disease, many research groups from both academia and pharmaceutical industry have sought to unravel how pathogenic mutations in PSEN cause presenile dementia. PSEN genes encode polytopic membrane proteins termed presenilins (PS1 and PS2), which function as the catalytic subunit of gamma-secretase, an intramembrane protease that has a wide spectrum of type I membrane protein substrates. Sequential cleavage of amyloid precursor protein by BACE and gamma-secretase releases highly fibrillogenic beta-amyloid peptides, which accumulate in the brains of aged individuals and patients with Alzheimer's disease. Familial Alzheimer's disease-associated presenilin variants are thought to exert their pathogenic function by selectively elevating the levels of highly amyloidogenic Abeta42 peptides. In addition to Alzheimer's disease, several recent studies have linked PSEN1 to familiar frontotemporal dementia. Here, we review the biology of PS1, its role in gamma-secretase activity, and discuss recent developments in the cell biology of PS1 with respect to Alzheimer's disease pathogenesis.
Diet and Colorectal Cancer: Still an Open Question
Authors: A. Schatzkin, L. S. Freedman, E. Lanza, J. Tangrea
Journal: JNCI Journal of the National Cancer Institute (1995)

The case implicating diet in the etiology of colorectal cancer—a disease that in this country kills each year nearly 60 000 men and women—is growing stronger. A wealth of ecologic, laboratory, and clinical nutrition data supports a diet-colorecta l cancer connection (7). Numerous observational epidemiologic studies indicate that risk of developing this malignancy is influenced by intake of fat (2), red (3) [and possibly cooked (4)] meat, fiber (5), resistant (nondigestible) starch (6), fruits and vegetables (7), folate (8), and other (9) dietary factors. In spite of the difficulties in establishing which dietary factors are decisive, an attractive integrative hypothesis is emerging: A dietary pattern characterized by low consumption of fat and red meat and high intake of fruits, vegetables, and grains substantially lowers colorectal cancer risk (1 JO). But the diet-large-bowel cancer case is not ironclad. Some epidemiologic studies (9,11) do not show the associations for dietary fat, red meat, or dietary fiber that have been observed in other studies. Moreover, people eating a lot of fat and red meat and few fruits and vegetables may differ from their low-fat- and low-red meat- and high-fruit- and high-vegetable-consuming counterparts in some characteristics that are the real causes of colorectal cancer. The inability of observational epidemiologic studies to rule out the existence of these confounding charac
Tolerance to oats in dermatitis herpetiformis
Authors: T Reunala, P Collin, K Holm, P Pikkarainen, A Miettinen, N Vuolteenaho, M Mäki
Journal: Gut (1998)

Objectives —Recent studies on coeliac disease have shown that oats can be included in a gluten-free diet without adverse effects on the small bowel. The presence of a rash is also a sensitive indicator of gluten ingestion in dermatitis herpetiformis, and this was used to study whether patients with this disease could also tolerate oats. Patients/Methods —Eleven patients with dermatitis herpetiformis in remission on a gluten-free diet were challenged daily with 50 g oats for six months. Clinical symptoms were recorded, serum samples taken, and skin and small bowel biopsies performed before and after the oat challenge. A control group comprised of 11 patients with dermatitis herpetiformis on a conventional gluten-free diet was also studied. Results —Eight patients challenged with oats remained asymptomatic, two developed a transient rash, and one withdrew because of the appearance of a more persistent but mild rash. Three of the 11 controls also developed a transient rash. IgA endomysial antibodies remained negative in all patients. The small bowel villous architecture, the densities of intraepithelial CD3 and α/β and γ/δ T cell receptor positive lymphocytes and crypt epithelial cell DR expression remained unaltered during the oat challenge. Conclusions —The results confirm the absence of oat toxicity on the gluten sensitive small bowel mucosa and suggest that the rash in patients with dermatitis herpetiformis is not activated by eating oats.
Loss of β2 microglobulin from the cell surface of cutaneous malignant and premalignant lesions
Authors: MARLYN L. TURBITT, RONA M. M. MACKIE
Journal: British Journal of Dermatology (1981)

Biopsies from twenty‐three patients with malignant skin lesions and from twenty‐two patients with premalignant or benign skin lesions were stained for β2 microglobulin by use of the immunoperoxidase technique. The results showed a significant loss of demonstrable surface β2 microglobulin from the surface of malignant cells compared to benign, and a partial loss in the premalignant cases. This difference could prove to be a useful tool in the histological diagnosis of malignant skin lesions, and in assessing whether or not the lesion has been completely excised.
Nucleotide sequence of the genes for tryptophan synthase in Pseudomonas aeruginosa.
Authors: A Hadero, I P Crawford
Journal: Molecular Biology and Evolution (1986)

We have determined the DNA sequence of the two adjacent genes for the alpha and beta chains of tryptophan synthase in Pseudomonas aeruginosa, along with 34 5'-flanking and 799 3'-flanking base pairs. The gene order is trpBA as predicted from earlier genetic studies, and the two cistrons overlap by 4 bp; a ribosome binding site for the second gene is evident in the coding sequence of the first gene. We have also determined the location of three large deletions eliminating portions of each gene. A detailed comparison of the deduced P. aeruginosa amino acid sequence with those published for E. coli, Bacillus subtilis, and Saccharomyces cerevisiae shows much similarity throughout the beta and most of the alpha subunit. Most of the residues implicated by chemical modification or mutation as being critical for enzymatic activity are conserved, along with many others, suggesting that three-dimensional structure has remained largely constant during evolution. We also report the construction of a recombinant plasmid that overproduces a slightly modified alpha subunit from P. aeruginosa that can form a functionally effective multimer with normal E. coli beta 2 subunit in vivo.
Iron overload in urban Africans in the 1990s
Authors: I T Gangaidzo, V M Moyo, T Saungweme, H Khumalo, R M Charakupa, Z A R Gomo, M Loyevsky, R Stearman, T La Vaute, E G Enquist, T A Rouault, V R Gordeuk
Journal: Gut (1999)

BACKGROUND In a previously described model, heterozygotes for an African iron loading locus develop iron overload only when dietary iron is high, but homozygotes may do so with normal dietary iron. If an iron loading gene is common, then homozygotes with iron overload will be found even in an urban population where traditional beer, the source of iron, is uncommon. AIMS To determine whether iron overload and the C282Y mutation characteristic of hereditary haemochromatosis are readily identifiable in an urban African population. METHODS Histological assessment, hepatocellular iron grading, and dry weight non-haem iron concentration were determined in post mortem tissue from liver, spleen, heart, lungs, and skin. DNA of subjects with elevated hepatic iron indexes was analysed for the C282Y mutation. Iron concentrations in other tissues were compared. RESULTS A moderate increase (&gt;30 μmol/g) in hepatic iron concentrations was found in 31 subjects (23%; 95% confidence interval 15.9 to 30.1%), and they were considerably elevated (&gt;180 μmol/g) in seven subjects (5.2%; 95% confidence interval 1.5 to 8.9%). Appreciably elevated hepatic iron concentrations were associated with heavy iron deposition in both hepatocytes and macrophages, and either portal fibrosis or cirrhosis. All were negative for the C282Y mutation. Very high concentrations were uncommon in subjects dying in hospital. Concentrations of iron in spleen, heart, lung, and skin were significantly higher in subjects with elevated hepatic iron. CONCLUSIONS Iron overload is readily identified among urban Africans and is associated with hepatic damage and iron loading of several tissues. The condition is unrelated to the genetic mutation found in hereditary haemochromatosis.
Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial
Authors: Lindsay E Fernández-Rhodes, Angela D Kokkinis, Michelle J White, Charlotte A Watts, Sungyoung Auh, Neal O Jeffries, Joseph A Shrader, Tanya J Lehky, Li Li, Jennifer E Ryder, Ellen W Levy, Beth I Solomon, Michael O Harris-Love, Alison La Pean, Alice B Schindler, CheunJu Chen, Nicholas A Di Prospero, Kenneth H Fischbeck
Journal: The Lancet Neurology (2011)
Fluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter study
Authors: J D Amsterdam, J Fawcett, F M Quitkin, F W Reimherr, J F Rosenbaum, D Michelson, M Hornig-Rohan, C M Beasley
Journal: American Journal of Psychiatry (1997)

Prior studies examining the relationship between fluoxetine plasma concentrations and response in major depression have either found no relationship between plasma concentration and response or suggested a curvilinear relationship with a therapeutic window. To elucidate this relationship, plasma concentrations of fluoxetine, norfluoxetine, fluoxetine plus norfluoxetine, and fluoxetine/norfluoxetine ratio were compared to therapeutic response.A total of 839 patients (577 women, 262 men; mean age = 40 [SD = 11] with a DSM-III-R diagnosis of major affective disorder who were in the course of either depression or bipolar disorder not otherwise specified and had a minimum baseline score of 16 on the 17-item Hamilton Depression Rating Scale were initially treated. Response was defined as follows: 1) nonresponders had less that a 50% or more reduction from baseline Hamilton depression score, 2) nonremitting responders had a 50% or more reduction from baseline Hamilton depression score but a final score higher than 7, and 3) remitters had a final Hamilton Depression score of 7 or lower. Plasma fluoxetine and norfluoxetine concentrations were measured after 8 weeks of fixed-dose treatment of 20 mg/day.Plasma concentration data were available from 615 patients. Plasma concentration were similar in responders, both remitting and nonremitting (N = 411), and nonresponders (N = 204) for fluoxetine concentrations, for norfluoxetine concentrations, as well as for the sum of fluoxetine and norfluoxetine and for the ratio of fluoxetine to norfluoxetine. No apparent relationship was observed between plasma drug concentration and clinical response.Plasma concentrations of fluoxetine and norfluoxetine do not appear to be related to clinical outcome and should not be used to make treatment decisions.
Contraception with Chlormadinone Acetate in Woman with Previous Contraceptive Jaundice
Authors: R. P. H. Thompson, R. Williams
Journal: BMJ (1970)

The oral contraceptive chlormadinone acetate has been given for eight months to a woman who had developed jaundice during four pregnancies, and twice while taking a combined contraceptive pill. No side-effects or changes in liver function were observed. This is further evidence that progestogens used for contraception, and in particular those derived from hydroxyprogesterone, are less hepatotoxic than the oestrogenic components.