tbuckley/cabot-search huggingface dataset:
Central Regulation of Hypothalamic-Pituitary-Thyroid Axis Under Physiological and Pathophysiological Conditions
Authors: Csaba Fekete, Ronald M. Lechan
Journal: Endocrine Reviews (2013)

TRH is a tripeptide amide that functions as a neurotransmitter but also serves as a neurohormone that has a critical role in the central regulation of the hypothalamic-pituitary-thyroid axis. Hypophysiotropic TRH neurons involved in this neuroendocrine process are located in the hypothalamic paraventricular nucleus and secrete TRH into the pericapillary space of the external zone of the median eminence for conveyance to anterior pituitary thyrotrophs. Under basal conditions, the activity of hypophysiotropic TRH neurons is regulated by the negative feedback effects of thyroid hormone to ensure stable, circulating, thyroid hormone concentrations, a mechanism that involves complex interactions between hypophysiotropic TRH neurons and the vascular system, cerebrospinal fluid, and specialized glial cells called tanycytes. Hypophysiotropic TRH neurons also integrate other humoral and neuronal inputs that can alter the setpoint for negative feedback regulation by thyroid hormone. This mechanism facilitates adaptation of the organism to changing environmental conditions, including the shortage of food and a cold environment. The thyroid axis is also affected by other adverse conditions such as infection, but the central mechanisms mediating suppression of hypophysiotropic TRH may be pathophysiological. In this review, we discuss current knowledge about the mechanisms that contribute to the regulation of hypophysiotropic TRH neurons under physiological and pathophysiological conditions.
Professional Behaviors of Physicians and Pursuing Social Justice—Reply
Authors: Darrell G. Kirch
Journal: JAMA (2009)

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 2022 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
Hepatocyte Membrane-Bound IgG and Circulating Liver-Specific Autoantibodies in Chronic Liver Disease: Relation to Hepatitis B Virus Serum Markers and Liver Histology
Authors: Riccardo Meliconi, Federico Miglio, M. Valeria Stancari, Mario Baraldini, G. Francesco Stefanini, Giovanni Gasbarrini
Journal: Hepatology (2007)

Hepatocytes isolated from 101 biopsies were examined for membrane-bound IgG. The sera of the patients were tested for anti-liver-specific lipoprotein by radioimmunoassay and for liver membrane autoantibody (by indirect immunofluorescence on isolated rabbit hepatocytes. The seven patients with normal liver or minor nonspecific alterations were negative for membrane IgG and serum antibodies. Membrane IgG with granular distribution was found in 41 patients [21 hepatitis B virus-related chronic active hepatitis (CAH), 3 cryptogenic CAH, 3 chronic persistent hepatitis, 6 prolonged viral hepatitis, 1 alcoholic cirrhosis, and 6 primary biliary cirrhosis]. Membrane IgG with linear fluorescence pattern was detected in 12 cases (4 autoimmune CAH, 3 HBsAg-positive CAH, 2 alcoholic cirrhosis, 1 anti-HBc positive CAH, 1 cryptogenic CAH, and 1 prolonged viral hepatitis). A strong association between granular IgG and serum HBsAg was found. Nuclear localization of IgG was found in 34 patients and correlated with the positivity of granular membrane IgG. The highest prevalence of anti-liver-specific lipoprotein was found in primary biliary cirrhosis and autoimmune CAH cases which were also positive for liver membrane autoantibody. No relationship was found between the presence of membrane IgG and circulating liver-specific autoantibodies. Membrane IgG and anti-liver-specific lipoprotein correlated with the presence of moderate and severe portal inflammatory infiltration but not with piecemeal necrosis or transaminase levels. Eleven of the twelve patients with linear membrane IgG presented chronic active liver disease with moderate to severe signs of liver damage. Therefore, it is suggested that, while granular membrane IgGs are related to hepatitis B virus, antigenic expression on the hepatocyte surface and/or the presence of immune complexes, linear membrane IgG could play a role in the immunopathogenesis of liver cell damage particularly in “autoimmune” cases which present high percentages of positive cells liver-specific autoantibodies.
Mechanism of Triglyceridemia in Hypercholesterolemic Rabbits
Authors: C. C. HUANG, K. J. KAKO
Journal: Circulation Research (1970)

To elucidate mechanisms responsible for the increased plasma triglyceride (TG) which occurs in diet-induced hypercholesterolemia in rabbits, albino rabbits were fed a 3% cholesterol diet for various durations, and the following determinations were carried out: plasma lipid levels; turnover rate of plasma TG (labeled very low density lipoprotein, or glycerol-2- 3 H method); lipoprotein lipase activity of the heart and plasma; fatty acid and acetate incorporation into TG in the liver (homogenates and slices). Plasma levels of both free and esterified cholesterol and phospholipid increased rapidly, while TG increased relatively slowly during cholesterol feeding without change in hepatic TG synthesis. The fractional turnover was, on the other hand, depressed within a week. The decrease in plasma TG in response to a heparin injection was less in hypercholesterolemic rabbits than in normal animals. However, the measured activity of heart lipoprotein lipase of cholesterol-fed rabbits was higher than that of the control group. When the effects of two substrates (very low density lipoprotein from normo- and from hypercholesterolemic plasma) were compared, the apparent activity was lower with the latter. The Degrees of this inhibition was proportional to the amount of cholesterol in the lipoproteins. The inhibition of lipoprotein lipase activity was also observed with the addition of cholesterol to activated Ediol, but not with addition of esterified cholesterol. Lineweaver-Burk plots were constructed using partially purified plasma lipoprotein lipase, and Km values for Ediol, Ediol plus protamine sulphate, and Ediol plus cholesterol were calculated. The presence of cholesterol in the substrate of lipoprotein lipase competitively inhibits the enzyme activity, and this is the mechanism of hyperglyceridemia observed in diet-induced hypercholesterolemic rabbits.
Emotional and Physical Precipitants of Ventricular Arrhythmia
Authors: Rachel Lampert, Tammy Joska, Matthew M. Burg, William P. Batsford, Craig A. McPherson, Diwakar Jain
Journal: Circulation (2002)

Observational studies have suggested that psychological stress increases the incidence of sudden cardiac death. Whether emotional or physical stressors can trigger spontaneous ventricular arrhythmias in patients at risk has not been systematically evaluated.Patients with implantable cardioverter-defibrillators (ICDs) were given diaries to record levels of defined mood states and physical activity, using a 5-point intensity scale, during 2 periods preceding spontaneously occurring ICD shocks (0 to 15 minutes and 15 minutes to 2 hours) and during control periods 1 week later. ICD-stored electrograms confirmed the rhythm at the time of shock. A total of 107 confirmed ventricular arrhythmias requiring shock were reported by 42 patients (33 men; mean age, 65 years; 78% had coronary artery disease) between August 1996 and September 1999. In the 15 minutes preceding shock, an anger level > or =3 preceded 15% of events compared with 3% of control periods (P<0.04; odds ratio, 1.83; 95% confidence intervals, 1.04 to 3.16) Other mood states (anxiety, worry, sadness, happiness, challenge, feeling in control, or interest) did not differ. Patients were more physically active preceding shock than in control periods. Anger and physical activity were independently associated with the preshock period.Anger and physical activity can trigger ventricular arrhythmias in patients with ICDs. Future investigations of therapies aimed at blocking a response to these stressors may decrease ventricular arrhythmias and shocks in these patients.
Letter: C-Film as contraceptive.
Authors: M Smith, M P Vessey, W Bounds, J Warren
Journal: BMJ (1974)

The Family Planning Association of London started a clinical trial to assess the efficacy and acceptability of C-Film as a sole method of contraception. 63 subjects were instructed to use 1 C-Film for each act of intercourse, to use no other contraceptive and to keep a monthly record card on dates of menstruation, days of intercourse, which partner used C-Film, if any, and the presence of vaginal symptoms. 18 of the 63 were not included in the analysis because 3 never cards. 9 of the 45 included in the analysis experienced involuntary pregnancy during a total of 175 person-months, representing a use-effectiveness pregnancy rate of 62/100 woman-years. Only 1 woman admitted to having an unprotected intercourse. A further 25 women withdrew from the trial because of side effects, difficulties with the method or reasons not connected with the method. Due to the unacceptably high failure rate, this study was terminated and the C-Film was not recommended as a sole method of contraception.
845 ONCE DAILY SOFOSBUVIR PLUS RIBAVIRIN FOR 12 AND 24 WEEKS IN TREATMENT-NAÏVE PATIENTS WITH HCV INFECTION: THE QUANTUM STUDY
Authors: J.P. Lalezari, D.R. Nelson, R.H. Hyland, M. Lin, S.J. Rossi, W.T. Symonds, M. Rodriguez-Torres, E.J. Lawitz
Journal: Journal of Hepatology (2013)
Rad9 Has a Functional Role in Human Prostate Carcinogenesis
Authors: Aiping Zhu, Charles Xia Zhang, Howard B. Lieberman
Journal: Cancer Research (2008)

Abstract Prostate cancer is currently the most common type of neoplasm found in American men, other than skin cancer, and is the second leading cause of cancer death in males. Because cell cycle checkpoint proteins stabilize the genome, the relationship of one such protein, Rad9, to prostate cancer was investigated. We found that four prostate cancer cell lines (CWR22, DU145, LNCaP, and PC-3), relative to PrEC normal prostate cells, have aberrantly high levels of Rad9 protein. The 3′-end region of intron 2 of Rad9 in DU145 cells is hypermethylated at CpG islands, and treatment with 5′-aza-2′-deoxycytidine restores near-normal levels of methylation and reduces Rad9 protein abundance. Southern blot analyses indicate that PC-3 cells contain an amplified Rad9 copy number. Therefore, we provide evidence that Rad9 levels are high in prostate cancer cells due at least in part to aberrant methylation or gene amplification. The effectiveness of small interfering RNA to lower Rad9 protein levels in CWR22, DU145, and PC-3 cells correlated with reduction of tumorigenicity in nude mice, indicating that Rad9 actively contributes to the disease. Rad9 protein levels were high in 153 of 339 human prostate tumor biopsy samples examined and detectable in only 2 of 52 noncancerous prostate tissues. There was a strong correlation between Rad9 protein abundance and cancer stage. Rad9 protein level can thus provide a biomarker for advanced prostate cancer and is causally related to the disease, suggesting the potential for developing novel diagnostic, prognostic, and therapeutic tools based on detection or manipulation of Rad9 protein abundance. [Cancer Res 2008;68(5):1267–74]
Grapefruit Juice and Kidney Stones
Authors: Barbara Ameer
Journal: Annals of Internal Medicine (1998)

Letters1 December 1998Grapefruit Juice and Kidney StonesBarbara Ameer, PharmDBarbara Ameer, PharmDPrinceton Jct, NJ 08550Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-11_Part_1-199812010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Of 17 beverages evaluated in Curhan and colleagues' cohort of more than 80 000 women in the United States, grapefruit juice was the only drink associated with increased risk for kidney stones [1]. This new health concern can be added to concern raised by the evidence of increased oral drug bioavailability by grapefruit juice [2].The mechanisms of these physiologic effects need to be elucidated. In the case of drug interactions, one or more components of grapefruit juice is thought to inhibit metabolic enzymes in the gastrointestinal tract or to inhibit a P-glycoprotein pump that transports drugs ...References1. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Beverage use and risk for kidney stones in women. Ann Intern Med. 1998; 128:534-40. Google Scholar2. Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Pharmacokinet. 1997; 33:103-21. Google Scholar3. Vinson JA, Jang J, Dabbagh YA, Serry MM, Cai S. Plant polyphenols exhibit lipoprotein-bound antioxidant activity using an in vitro oxidation model for heart disease. J Agric Food Chem. 1998; 43:2798-9. Google Scholar4. Ameer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL. Flavanone absorption after naringin, hesperidin and citrus administration. Clin Pharmacol Ther. 1996; 60:34-40. Google Scholar Author, Article, and Disclosure InformationAuthors: Barbara Ameer, PharmDAffiliations: Princeton Jct, NJ 08550 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGrapefruit: the last decade acquisitions 1 December 1998Volume 129, Issue 11_Part_1Page: 913KeywordsCalciumDrug interactionsDrugsFlavonoidKidney stonesLow density lipoproteinOral healthRenal systemTeaUrine ePublished: 15 August 2000 Issue Published: 1 December 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Efficacy of Lenalidomide in Myelodysplastic Syndromes
Authors: Alan List, Sandy Kurtin, Denise J. Roe, Andrew Buresh, Daruka Mahadevan, Deborah Fuchs, Lisa Rimsza, Ruth Heaton, Robert Knight, Jerome B. Zeldis
Journal: New England Journal of Medicine (2005)

Ineffective erythropoiesis is the hallmark of myelodysplastic syndromes. Management of the anemia caused by ineffective erythropoiesis is difficult. In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the safety and hematologic activity of lenalidomide, a novel analogue of thalidomide.Forty-three patients with transfusion-dependent or symptomatic anemia received lenalidomide at doses of 25 or 10 mg per day or of 10 mg per day for 21 days of every 28-day cycle. All patients either had had no response to recombinant erythropoietin or had a high endogenous erythropoietin level with a low probability of benefit from such therapy. The response to treatment was assessed after 16 weeks.Neutropenia and thrombocytopenia, the most common adverse events, with respective frequencies of 65 percent and 74 percent, necessitated the interruption of treatment or a dose reduction in 25 patients (58 percent). Other adverse events were mild and infrequent. Twenty-four patients had a response (56 percent): 20 had sustained independence from transfusion, 1 had an increase in the hemoglobin level of more than 2 g per deciliter, and 3 had more than a 50 percent reduction in the need for transfusions. The response rate was highest among patients with a clonal interstitial deletion involving chromosome 5q31.1 (83 percent, as compared with 57 percent among those with a normal karyotype and 12 percent among those with other karyotypic abnormalities; P=0.007) and patients with lower prognostic risk. Of 20 patients with karyotypic abnormalities, 11 had at least a 50 percent reduction in abnormal cells in metaphase, including 10 (50 percent) with a complete cytogenetic remission. After a median follow-up of 81 weeks, the median duration of transfusion independence had not been reached and the median hemoglobin level was 13.2 g per deciliter (range, 11.5 to 15.8).Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy.
Chemical Estimation of Cortisone-like Hormones in Urine
Authors: C. L. Cope, B. Hurlock
Journal: BMJ (1952)

TUBERCULOSIS sDIJsHAL the most important questions-for example, the risk of meningitis at different ages-and that I do not think children with asymptomatic primary infection should be treated in sanatoria unless home circumstances are unfavourable, or by antibiotics except under very special circumstances.These children should nevertheless remain under regular supervision and a close watch be kept for signs of disseminated disease.Knowledge of the primary complex is, moreover, of great assistance in detecting the early case of tuberculous meningitis or miliary tuberculosis, in which the prognosis depends almost entirely upon the time interval between onset and the beginning of treatment.The routine use of streptomycin and P.A.S. cannot be recommended, but in cases of prolonged fever of onset, or when the infant is infected in the first year and is febrile or losing weight, or in certain cases of tuberculous cervical lymphadenitis, these compounds are of very real value.Finally, I would repeat my plea that, wherever home care is competent and conditions are good, children with primary tuberculosis who do require treatment should be kept at home or be allowed to go home as soon as possible after confirmation of the diagnosis in hospital.This applies particularly to the child under the age of 5 years, who should be admitted to a " long-stay" hospital only when no other course is possible.We must strike a careful balance between the chance of diminishing the risk of disseminated disease and improv- ing the child's physical state and the chance of inter- fering with or distorting his emotional development by long separation from home and parents.
Sustained disease remission after spontaneous HBeAg seroconversion is associated with reduction in fibrosis progression in chronic hepatitis B Chinese patients
Authors: Chee-Kin Hui, Nancy Leung, Tony W.H. Shek, Hung Yao, Wai-Ki Lee, Jak-Yiu Lai, Sik-To Lai, Wai-Man Wong, Lawrence SW. Lai, Ronnie T.P. Poon, Chung-Mau Lo, Sheung-Tat Fan, George K.K. Lau
Journal: Hepatology (2007)

Recently, controversies have arisen about whether hepatitis B e antigen (HBeAg) seroconversion can result in regression of fibrosis, thus improving the clinical outcome of Chinese patients with chronic hepatitis B. In this study, we determined if spontaneous HBeAg seroconversion is associated with regression of fibrosis in Chinese chronic hepatitis B patients. We evaluated the histology of liver samples from 128 HBeAg-positive treatment-naive Chinese patients who had undergone 2 liver biopsies over the years. Regression of fibrosis was defined as a decrease in fibrosis stage of at least 1 point. Sustained disease remission was defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 10(4) copies/ml at follow-up liver biopsy. The mean duration (+/- standard error of the mean) between the initial and follow-up liver biopsies was 43.9 +/- 3.4 months. Regression of fibrosis was higher in patients with sustained disease remission (5 of 13 [38.5%] versus 22 of 115 [19.1%], P < 0.00005), patients who were younger (20-29 years old) at initial liver biopsy (17 of 54 [31.5%] versus 10 of 74 [13.5%], P = 0.0004), and patients with genotype B (17 of 43 [39.5%] versus 10 of 85 [11.8%], P = 0.004). On multivariate analysis, sustained disease remission (relative risk [RR] 3.00, 95% confidence interval [95% CI] 1.29-7.01, P = 0.01) and being 20-29 years old at initial liver biopsy (RR 2.94, 95% CI 1.01-8.62, P = 0.04) were independently associated with regression of fibrosis. The rate of fibrosis progression was lower in patients with sustained disease remission than in those who remained HBeAg positive (median 0 fibrosis units/year, range -2.00 to -0.70 fibrosis units/year, versus median 0.51 fibrosis units/year, range 0 to +2.03 fibrosis units/year, P = 0.02).Spontaneous sustained remission of disease is associated not only with little progression of fibrosis but also with regression of fibrosis.
Outcome and Cost for Stroke Patients in Academic and Community Hospitals
Authors: Joel S. Feigenson, Walter D. Feigenson, Howard S. Gitlow, Mary Lou McCarthy, Susan D. Greenberg
Journal: JAMA (1978)

Patients transferred to a regional stroke rehabilitation center from academic hospital centers (124 patients) and from community hospital centers (315 patients) were compared for outcome and cost of treatment. The two groups were matched for Amended International Classification of Disease diagnostic category, age, sex, distribution of weakness, types of neurological deficits, time from the onset of the stroke symptoms to admission to the rehabilitation unit, and the concurrence of major medical problems thought to contribute to cerebrovascular disease. There was no statistically significant difference in functional outcome or length of stay, but acute health care costs for patients treated in community hospitals were about 50% less. (<i>JAMA</i>240:1878-1880, 1978)
Sequence Analysis of Transposable Elements in the Sea Squirt, Ciona intestinalis
Authors: Martin W. Simmen, Adrian Bird
Journal: Molecular Biology and Evolution (2000)

A systematic search of 1 Mb of genomic sequences from the sea squirt, Ciona intestinalis, revealed the presence of six families of transposable elements. The Cigr-1 retrotransposon contains identical 245-bp long terminal repeats (LTRs) and a 3,630-bp open reading frame (ORF) encoding translation products in the same order as the domains characteristic of gypsy/Ty3-type LTR retrotransposons. The closest homologs of the reverse transcriptase domain were in gypsy elements from Drosophila and the sushi element from the pufferfish. However, the capsid-nucleocapsid region shows the clearest homology to an echinoderm element, Tgr1. Database searches also indicated two classes of non-LTR retrotransposon, named Cili-1 and Cili-2. The Cili-1 sequences show matches to regions of the ORF2 product of mammalian L1 elements. The Cili-2 sequences possess similarity to the RNaseH domain of Lian-Aa1, a mosquito non-LTR retrotransposon. The most abundant element was a short interspersed nucleotide element named Cics-1 with a copy number estimated at 40,000. Cics-1 consists of two conserved domains separated by an A-rich stretch. The 172-bp 5′ domain is related to tRNA sequences, whereas the 110-bp 3′ domain is unique. Cics-1 is unusual, not just in its modular structure, but also in its lack of a 3′ poly(A) tail or direct flanking repeats. A second abundant element, Cimi-1, has an A+T-rich 193-bp consensus sequence and 30-bp terminal inverted repeats (TIRs) and is usually flanked by A+T-rich 2–4-bp putative target site duplications—characteristics of miniature inverted-repeat transposable elements found in plants and insects. A single 2,444-bp foldback element was found, possessing long TIRs containing an A+T-rich internal domain, an array of subrepeats, and a flanking domain at the TIR ends; this is the first example of a chordate foldback element. This study provides the first systematic characterization of the families of transposable elements in a lower chordate.