tbuckley/cabot-search huggingface dataset:
Desensitization of postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses in rat harboring pheochromocytoma.
Authors: G Tsujimoto, K Honda, B B Hoffman, K Hashimoto
Journal: Circulation Research (1987)

Prolonged stimulation of tissues by adrenergic agonists may lead to diminished responsiveness of the tissues to subsequent activation by catecholamines; this phenomenon has been termed desensitization or tachyphylaxis. We have examined the in vivo consequences of prolonged stimulation of vascular alpha-adrenergic receptors in rats harboring pheochromocytoma, a tumor that secretes catecholamines. In both early (3-4 weeks after implantation) and late (6-7 weeks after implantation) stages of tumor development, New England Deaconess Hospital rats with transplanted pheochromocytomas developed hypertension and tachycardia and had plasma dopamine and norepinephrine concentrations markedly greater than controls. In both these stages of pheochromocytoma, pressor responses to several vasoconstrictors were examined after pithing. Rats with the tumor were found to become progressively subsensitive to alpha-adrenergic agonists. In the early phase of pheochromocytoma, loss in sensitivity was found for both alpha 1- and alpha 2-adrenergic agonists, whereas responsiveness to the nonadrenergic vasoconstrictors Arg-vasopressin and angiotensin-II was intact (homologous desensitization). However, in the later stage of pheochromocytoma, pressor responses to all these vasoconstrictive agents and also to stimulation of the complex sympathetic outflow were found to be subsensitive (heterologous desensitization). In plasma membranes prepared from mesenteric arteries of early stage tumor-bearing rats, [3H]prazosin binding sites were significantly decreased to 150 +/- 12 fmol/mg vs. 234 +/- 19 fmol/mg in controls. [3H]Yohimbine binding sites were not significantly altered. Our results show that both postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses can be specifically attenuated in the presence of chronically elevated endogenous catecholamine levels produced by pheochromocytoma and that each alpha-receptor subtype may be differently regulated in the development of desensitization.
PGC-1alphaas modifier of onset age in Huntington disease
Authors: Elahe Taherzadeh-Fard, Carsten Saft, Jürgen Andrich, Stefan Wieczorek, Larissa Arning
Journal: Molecular Neurodegeneration (2009)

Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In > 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modifying effects on the pathogenic process in HD.
Heparan Sulfate of Perlecan Is Involved in Glomerular Filtration
Authors: Hiroyuki Morita, Ashio Yoshimura, Kiyoko Inui, Terukuni Ideura, Hideto Watanabe, Ling Wang, Raija Soininen, Karl Tryggvason
Journal: Journal of the American Society of Nephrology (2005)

Perlecan is a heparan sulfate proteoglycan and a major component of the glomerular basement membrane. To understand the role of heparan sulfate chains of perlecan in glomerular filtration, detailed analyses were performed of the kidneys of Hspg2(Delta)(3/)(Delta)(3) mice, whose perlecan lacks heparan sulfate attachment sites in N-terminal domain I. Macroscopic, histologic, and electron microscopic observations, as well as immunohistochemical and immunoelectron microscopic analyses using specific antibodies against perlecan and agrin core proteins, revealed no significant abnormalities in these mice under physiologic conditions. Polyethyleneimine staining demonstrated no significant changes in charge density in the glomerular basement membrane. Transcripts of other heparan sulfate proteoglycans, agrin, and collagen type XVIII, as well as perlecan, were expressed at similar levels to those in the wild-type littermates. Approximately 40% of the perlecan synthesized by Hspg2(Delta)(3/)(Delta)(3) fibroblasts was substituted with heparin sulfate and 60% was substituted with chondroitin sulfate. All of the perlecan synthesized by wild-type fibroblasts contained heparin sulfate, indicating an altered substitution of glycosaminoglycans on Hspg2(Delta)(3/)(Delta)(3) perlecan. Immunostaining indicated that the level of chondroitin sulfate was actually increased in the Hspg2(Delta)(3/)(Delta)(3) glomerular basement membrane. When administered intraperitoneally with BSA, Hspg2(Delta)(3/)(Delta)(3) mice exhibited remarkable proteinuria. These findings suggest that heparan sulfate chains of perlecan play an important role in glomerular filtration, especially of a large amount of protein.
Points from letters: Consultants' incremental pay
Authors: G Evison
Journal: BMJ (1975)

October, p 25) is not alone.At the inception of the NHS in 1948 I was an assistant in general practice and lived above the surgery in a traffic-congested area.At that time I managed my rounds quite easily on a bicycle.Unfortunately both your clientele and your colleagues come to regard you as an outsider, which adds to your emotional burden.The car becomes your
Risk Factors for Suicides Among Army Personnel
Authors: Matthew J. Friedman
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 2941: The role of lysine acetylation in the tumor cell response to stress.
Authors: Lisa Heppler, Joshua L. Andersen
Journal: Cancer Research (2013)

Abstract Solid breast tumors contain heterogenous microenvironments where tumor cells are often exposed to metabolic stress (e.g., hypoxia due to poor blood supply). Such environments select for tumor cells that can adapt metabolically to survive, while other cells fail to adapt and undergo cell death. The survival of cells through periods of hypoxia can promote chemoresistance and metastasis (1). Thus, it is critical that we develop therapeutic strategies to enhance metabolic-stress-induced tumor cell death. One promising strategy is the modulation of lysine acetylation pathways by HDAC inhibitors that potently promote cell death in response to various stimuli, including hypoxia/glucose withdrawal. Given the relatively non-specific nature of chemical HDAC inhibitors, the precise acetylation-regulating enzymes and pathways that govern cell death in these settings have yet to be fully elucidated. Our goal is to identify the cellular factors that link acetylation to cell death in response to hypoxia and other metabolic stresses, with the hope that such factors could be exploited therapeutically in cancer. Previous studies have implicated protein lysine acetylation in the coordination of cellular metabolism to the available nutrient supply (2). In line with this idea, our preliminary data suggest that lysine acetylation pathways dictate whether breast tumor cells survive (through metabolic adaptation) or die in response to hypoxia and glucose deprivation. Moreover, we have observed that general increases in protein lysine acetylation precede the activation of pro-apoptotic caspases in response to these stresses. In addition, our proteomics efforts have shown that breast tumors that are sensitive to hypoxia/glucose withdrawal exhibit significant increases in acetylation across the proteome, whereas resistant cells show very little change. Together, our data suggest that lysine acetylation pathways play a role in metabolic adaption and survival under conditions of hypoxia/glucose withdrawal. We are currently using an RNAi approach to target all known deacetylases, acetyl-transferases, and metabolic enzymes that modulate acetylation (e.g., acetyl-CoA synthetase) in order to identify the specific acetylation-regulating factors that govern tumor cell susceptibility to metabolic stress. Citation Format: Lisa Heppler, Joshua L. Andersen. The role of lysine acetylation in the tumor cell response to stress. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2941. doi:10.1158/1538-7445.AM2013-2941
Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced qacute renal failure
Authors: T. Matsuzaki, H. Watanabe, K. Yoshitome, T. Morisaki, A. Hamada, H. Nonoguchi, Y. Kohda, K. Tomita, K. Inui, H. Saito
Journal: Kidney International (2007)
Gates foundation pledges new funds to fight neglected diseases
Authors: J. Zarocostas
Journal: BMJ (2009)

The Bill and Melinda Gates Foundation and private business have separately pledged new funds to combat, respectively, neglected tropical diseases and malaria.

Bill and Melinda Gates, in a press conference at the annual world economic forum in Davos, Switzerland, announced that they were giving a grant of $34m (£24m; €27m) to the Global Network for Neglected Tropical Diseases to help curb, by 2020, the most prevalent diseases that affect about 1.4 billion of the world’s poorest people.

The network confirmed receipt of the grant to the Sabin Vaccine Institute to step up global efforts to prevent and treat neglected tropical diseases.

“We’re living in very difficult …
Vaccination Problems for Parliament
Authors: J. C. McVail
Journal: BMJ (1902)

omnibuses, the lifts of the Tube Railway, and similar places, where the risk of their having conveyed infection broadcast is very considerable.Such risks cannot by any amount of aiministrative zeal be avoided or removed.It is, however,no doubt very desirable, especially in densely crowded localities and houses, to remove each case of small-pox when recognized, and to surround it, at small-pox hospitals, with a cordon of people well protected by efficient vaccination.The duty of doing this has been assigned to the Metropolitan Asylums Board, a body which was created by the Metropolitan Poor Act of I867.Its managers number 73.Of these, i8 are nominated by the Local Government Board, and the rest are chosen by the Boards of Guardians from among themselves.The Asylums Board is under the immediate control of the Local Government Board, and it is in no way responsible to the borough councils or vestries.It is defined as a "sanitary authority for the prevention of epidemic disease;" it would be more accurate to speak of "the limitation" rather than " the prevention" of such disease.It deals with infectious fevers, small-pox, and diphtheria, and also with defective children and imbeciles.It takes charge of the ambulance service of London.It has under its care twelve large fever hospitals, small-pox hospital ships on river and land, con- valescent hospitals, land ambulance stations and wharves, hospitals for imbeciles, etc. Admission into any one of the hospitals under the Asylums Board is not equivalent to receiving parochial relief or alms, although the expenses incurred for the maintenance of such person are paid by the guardians of the Poor-law union from which he is received, and though the guardians are repaid out of the Metropolitan Common Poor Fund.2
Postpartum acute renal failure: possible role for endarterial urokinase.
Authors: M Cochran, J F Martin, B Ross
Journal: BMJ (1977)

Postpartum acute renal failure: possible role for endarterial urokinase Late postpartum acute renal failure is a rare complication of the puerperium, which, together with its insidious onset, probably explains why renal damage is generally irreversible by the time of diagnosis.It is important to note that the fully developed syndrome is usually preceded by definite, albeit non-specific, prodromal sym- toms. Case reportA 26-year-old gravida 5 (group A, rr; HLA 1, 2, and 8, W39) appeared to be well aft_r an uncomplicated pregnancy.Two weeks post partum, however, she developed headaches and mild ankle oedema, and four weeks later she became anuric.Plasma urea was 48 mmol/l (289 mg/100 ml), haemoglobin was 7-1 g/dl, fragmented red cells were seen, platelets were 160 K 109/1 (160 000/mm3), and plasma fibrinogen was 7-5 g/l.Renal biopsy
Preliminary Laryngeal Examination During Magnifying Upper Gastrointestinal Video Endoscopy in Two Patients with Reflux Symptoms
Authors: G. Cammarota, S. Agostino, M. Rigante, P. Cesaro, C. Parrilla, R. La Mura, G. Gasbarrini, J. Galli
Journal: Endoscopy (2006)

A 59-year-old man (with a 40-year-long history of smoking) and a 53-year-old woman were referred because of reflux symptoms, such as heartburn and regurgitation, associated with dysphonia, chronic throat clearing and globus pharyngeus. The man had undergone Billroth II gastrectomy 29 years previously, while the woman had a history of cholecystectomy 32 years previously.
Novel Anchorage of GluR2/3 to the Postsynaptic Density by the AMPA Receptor–Binding Protein ABP
Authors: S Srivastava, P Osten, F.S Vilim, L Khatri, G Inman, B States, C Daly, S DeSouza, R Abagyan, J.G Valtschanoff, R.J Weinberg, E.B Ziff
Journal: Neuron (1998)

We report the cloning of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor–binding protein (ABP), a postsynaptic density (PSD) protein related to glutamate receptor–interacting protein (GRIP) with two sets of three PDZ domains, which binds the GluR2/3 AMPA receptor subunits. ABP exhibits widespread CNS expression and is found at the postsynaptic membrane. We show that the protein interactions of the ABP/GRIP family differ from the PSD-95 family, which binds N-methyl-D-aspartate (NMDA) receptors. ABP binds to the GluR2/3 C–terminal VKI-COOH motif via class II hydrophobic PDZ interactions, distinct from the class I PSD-95–NMDA receptor interaction. ABP and GRIP also form homo- and heteromultimers through PDZ–PDZ interactions but do not bind PSD-95. We suggest that the ABP/GRIP and PSD-95 families form distinct scaffolds that anchor, respectively, AMPA and NMDA receptors.
Surveillance, Diagnosis, Treatment, and Outcome of Liver Cancer in Japan
Authors: Masatoshi Kudo
Journal: Liver Cancer (2015)

&lt;b&gt;&lt;i&gt;Background: &lt;/i&gt;&lt;/b&gt;Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the third leading cause of cancer-related death worldwide. HCC is most common in Asia, but its prevalence is rapidly increasing in Western countries; consequently, HCC is a global medical issue that urgently needs to be addressed. Japan is the only developed country that has experienced both hepatitis B-related and hepatitis C-related HCC and has a long history of innovation when it comes to new diagnostic and therapeutic modalities, such as computed tomography angiography, anatomical resection, ablation, and transarterial chemoembolization. Among these innovations, a nationwide surveillance program was well established by the 1980s, and such a long-term national program does not exist anywhere else in the world. &lt;b&gt;&lt;i&gt;Summary: &lt;/i&gt;&lt;/b&gt;More than 60% of the initially detected HCCs in Japan are Barcelona Clinic Liver Cancer stage 0 or A, which can undergo curative therapies such as resection, ablation, or transplantation. The recent 5-year survival rate of HCC patients in Japan was 43% and the median survival time was 50 months. In addition, both incidence and mortality rates are drastically declining as a result of the successful surveillance program, careful diagnostic flow, and extensive repeated treatments. &lt;b&gt;&lt;i&gt;Key Message: &lt;/i&gt;&lt;/b&gt;Japan's successful model in the surveillance, diagnosis, and treatment of HCC should be adopted as widely as possible to improve the survival of HCC patients worldwide.
Dopamine D1-like Receptor Antagonist Attenuates TH17-mediated Immune Response and Ovalbumin-antigen Induced Neutrophilic Airway Inflammation
Authors: K. Nakagome, H. Okada, M. Imamura, K. Kawahata, T. Inoue, K. Hashimoto, F. Nishihara, H. Harada, Y. Takaku, T. Kobayashi
Journal: Journal of Allergy and Clinical Immunology (2011)
The Illness Process
Authors: Morton R. Weinstein
Journal: JAMA (1968)

Recent studies of disability following industrial accidents illustrate an "accident process" in which social and emotional conflicts are resolved by substituting the "acceptable" disability of injury for the "unacceptable" disability of tension and depression. Aid to the Needy Disabled and other disability programs can become part of an analogous "illness process" in which medical impairment becomes the "acceptable" solution to a patient's longstanding conflicts in living. When disability programs serve this purpose, they vitiate efforts to reduce the social and emotional tensions which really disable the patient. Physicians can be trained to elicit and interpret the information necessary to understand the development of the "illness process." Health professionals must learn how to help patients find less costly ways of coping with conflict than through the pseudosolution of chronic disability.
Minor contribution of hepatocytes to collagen production in normal and early fibrotic rat livers
Authors: Itsuro Ogata, Satoshi Mochida, Tomoaki Tomiya, Kenji Fujiwara
Journal: Hepatology (1991)

Hepatocyte contribution to hepatic collagen production in vivo was estimated in rats, based on the fact that ornithine is used for protein synthesis in the liver as arginine after conversion by way of the urea cycle only by hepatocytes. From rats given a mixture of [14C] ornithine and [3H]arginine, hepatic collagen and serum albumin were obtained. The hepatocyte contribution was calculated from the 14C and 3H in arginine purified from collagen and albumin by high performance liquid chromatography. The contribution was less than 10% of total collagen production in normal and early fibrotic livers induced by a single dose of carbon tetrachloride or dimethylnitrosamine. We conclude that hepatocytes may play a minor role in collagen production in normal and early fibrotic rat livers.
Circulating cellular fibronectin may be a natural ligand for the hepatic asialoglycoprotein receptor: Possible pathway for fibronectin deposition and turnover in the rat liver
Authors: Robert F. Rotundo, Robert A. Rebres, Paula J. Mckeown-Longo, Frank A. Blumenstock, Thomas M. Saba
Journal: Hepatology (1998)

It has been postulated that the in vivo removal of many plasma glycoproteins after desialylation is mediated by their interaction with a specific endocytic receptor on hepatocytes called the asialoglycoprotein receptor (ASGP-R), which is known to have a high affinity for specific carbohydrate residues, such as galactose. However, this mechanism has never been proven in vivo, nor has a naturally occurring ligand for the ASGP-R been identified. We investigated the influence of the terminal galactose residues on plasma fibronectin (pFn) on its liver deposition and turnover in adult rats, using neuraminidase to remove sialic acid residues to expose galactose residues. We also tested the hypothesis that the normal presence of a large amount of terminal galactose residues in cellular Fn (cFn) may allow cFn to serve as a natural ligand readily able to interact with the ASGP-R. In contrast to the slow clearance of normal pFn from the blood, cFn and desialylated pFn (aFn) displayed a rapid plasma clearance (P < .001) with greater than 50% of both the 125I-cFn or 125I-aFn depositing in the liver within 15 minutes. The enhanced plasma removal and liver deposition of both 125I-cFn and 125I-aFn was competitively inhibited (P < .01) by prior intravenous infusion of excess asialofetuin, which can selectively bind to the ASGP-R. The enzymatic addition of terminal sialic acid residues onto cFn to "mask" or "cap" the normally exposed galactose residues delayed the rapid plasma removal of cFn. Accelerated degradation of 125I-aFn and 125I-cFn as compared with 125I-pFn was demonstrated in vitro by both primary cultures of normal rat hepatocytes or incubated (37 degrees C) tissue slices of livers harvested from normal rats after in vivo preloading with tracer 125I-Fn forms. Thus, the ASGP-R appears to directly participate in the rapid in vivo removal of cFn from the blood, while native pFn may be removed by an alternative pathway unless it can become desialylated in vivo. These findings suggest that cFn may be a naturally occurring ligand that does not require desialylation before removal by the ASGP-R on hepatocytes.
Toxic epidermal necrolysis associated with severe hypocalcaemia, and treated with cyclosporin
Authors: I. Zaki, S. Patel, R. Rreed, K.L. Dalziel
Journal: British Journal of Dermatology (1995)

Journal Article Toxic epidermal necrolysis associated with severe hypocalcaemia, and treated with cyclosporin Get access I. Zaki, I. Zaki Department of Dermatology, University Hospital Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Patel, S. Patel Department of Medicine, City Hospital, Nottingham, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Rreed, R. Rreed Department of Medicine, City Hospital, Nottingham, U.K. Search for other works by this author on: Oxford Academic Google Scholar K.L. Dalziel K.L. Dalziel Department of Dermatology, University Hospital Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 2, 1 August 1995, Pages 337–338, https://doi.org/10.1111/j.1365-2133.1995.tb02649.x Published: 01 August 1995