tbuckley/cabot-search huggingface dataset:
Defective HDL particle uptake in ob/ob hepatocytes causes decreased recycling, degradation, and selective lipid uptake
Authors: David L. Silver, Nan Wang, Alan R. Tall
Journal: Journal of Clinical Investigation (2000)

Levels of plasma HDL are determined in part by catabolism in the liver. However, it is unclear how the hepatic catabolism of holo-HDL is regulated or mediated. Recently, we found that ob/ob mice have defective liver catabolism of HDL apoproteins in vivo that can be reversed by low-dose leptin treatment. Here we examined HDL catabolism and trafficking at the cellular level using isolated hepatocytes. We demonstrate that ob/ob hepatocytes have reduced binding, association, degradation, and resecretion of HDL apoproteins and 50% less selective lipid uptake relative to wild-type hepatocytes. In addition, HDL apoproteins were found to colocalize with transferrin in the general endosomal recycling compartment (ERC) in wild-type hepatocytes. However, the localization to the ERC was markedly reduced in ob/ob hepatocytes. Filipin staining of cellular cholesterol revealed decreased cholesterol in the ERC in ob/ob hepatocytes. Defects in HDL cell association and cholesterol distribution were reversed by leptin administration. The findings show a major defect in HDL uptake and recycling in ob/ob hepatocytes and suggest that HDL recycling through the ERC plays a role in the determination of plasma HDL protein and cholesterol levels.
Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections
Authors: Amandine Crequer, Anja Troeger, Etienne Patin, Cindy S. Ma, Capucine Picard, Vincent Pedergnana, Claire Fieschi, Annick Lim, Avinash Abhyankar, Laure Gineau, Ingrid Mueller-Fleckenstein, Monika Schmidt, Alain Taieb, James Krueger, Laurent Abel, Stuart G. Tangye, Gérard Orth, David A. Williams, Jean-Laurent Casanova, Emmanuelle Jouanguy
Journal: Journal of Clinical Investigation (2012)

Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most, but not all, patients with autosomal recessive EV. We found that 2 young adult siblings presenting with T cell deficiency and various infectious diseases, including persistent EV-HPV infections, were homozygous for a mutation creating a stop codon in the ras homolog gene family member H (RHOH) gene. RHOH encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients' circulating T cells contained predominantly effector memory T cells, which displayed impaired TCR signaling. Additionally, very few circulating T cells expressed the β7 integrin subunit, which homes T cells to specific tissues. Similarly, Rhoh-null mice exhibited a severe overall T cell defect and abnormally small numbers of circulating β7-positive cells. Expression of the WT, but not of the mutated RHOH, allele in Rhoh-/- hematopoietic stem cells corrected the T cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH deficiency leads to T cell defects and persistent EV-HPV infections, suggesting that T cells play a role in the pathogenesis of chronic EV-HPV infections.
Stem Cell Legislation
Authors: Mike Mitka
Journal: JAMA (2007)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Code of practice on managing tuberculosis is satisfactory
Authors: P. Ormerod, J. Watson, C. Skinner
Journal: BMJ (1996)

EDITOR,—Julia E Clark and Andrew J Cant report three cases of childhood tuberculosis and discuss their management in relation to the 1994 code of practice of the joint tuberculosis committee of the British Thoracic Society.1 2 They conclude that all children in contact with tuberculosis should have a chest x ray examination irrespective of the result of the initial tuberculin test. We do not believe that this recommendation is justified for the …
Information for Readers
Authors: Elaine S. Williams, George D. Lundberg
Journal: JAMA (1998)

We hereby thank the 3276 peer reviewers who completed JAMA manuscript reviews in 1997 and whose names appear on pages 1127-1138. JAMA received 4233 manuscripts in 1997. The total acceptance rate was 16.2%, and the acceptance rate for unsolicited manuscripts was 10.8%.
QUANTITATIVE RELATIONSHIPS BETWEEN THE IMMUNIZING DOSE OF EPIDEMIC INFLUENZA VIRUS AND THE RESULTANT IMMUNITY
Authors: Thomas Francis
Journal: The Journal of Experimental Medicine (1939)

A direct proportion exists between the concentration of epidemic influenza virus used for intraperitoneal immunization of mice and the degree of immunity to intranasal infection which develops. Mice vaccinated with virus of a given strength resist infection with virus of the same concentration but not more. An irreducible minimum exists since mice vaccinated with less than ten intranasal lethal doses do not develop sufficient immunity to overcome intranasal infection with virus of the same strength. The fact that there exists a limiting threshold for the degree of immunity which a certain strength of virus will induce indicates that the virus does not multiply after intraperitoneal inoculations. In ferrets a state of partial immunity is induced as a result of subcutaneous vaccination with active influenza virus. Vaccination with doses containing 100 or more intranasal infectious units is required for the production of circulating antibodies, protection of the animals from pulmonary involvement, and modification of the severity of the disease. On the other hand, intranasal inoculation with one infectious unit results in a firm, immediate immunity, although the duration of immunity may bear a relation to the severity of the original infection and consequently to the size of the infecting dose. Ferrets in a state of partial immunity resulting from subcutaneous vaccination, or from the waning of a firm immunity following infection, respond to intranasal inoculation of influenza virus with an accelerated production of neutralizing antibodies. The antibody titer under these conditions reaches a much higher level than occurs following a primary infection. Fully immune animals, however, show no further antibody response to a second inoculation.
Profile of urinary arsenic metabolites during pregnancy.
Authors: Claudia Hopenhayn, Bin Huang, Jay Christian, Cecilia Peralta, Catterina Ferreccio, Raja Atallah, David Kalman
Journal: Environmental Health Perspectives (2003)

Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic.
Acromegaly: Reassessment of the Long-term Therapeutic Effectiveness of Transsphenoidal Pituitary Surgery
Authors: Lawrence D. Schuster, John P. Bantle, Jack H. Oppenheimer, Edward L. Seljeskog
Journal: Annals of Internal Medicine (1981)

Of 11 patients with active acromegaly treated with transsphenoidal selective pituitary adenomectomy, four failed to show evidence of clinical improvement. An additional four patients showed clinical and biochemical improvement after the surgical procedure but, with more prolonged follow-up, showed a recurrence of acromegaly. Only three patients had prolonged clinical and biochemical evidence of improvement; they had glucose suppressed growth hormone concentrations of 1.0, 2.7, and 2.8 ng/mL 22, 40, and 24 months, respectively, after the surgical procedure. Two of these three patients, however, showed an increase in growth hormone concentration after thyrotropin-releasing hormone injection, a finding that suggests the possibility of eventual relapse. Our data also clearly indicated a need for more rigorous criteria for biochemical cure of acromegaly than those used previously. Study of 20 healthy volunteers showed that growth hormone concentration should normally be suppressible to less than 2.0 ng/mL after 100 g oral glucose.
Advances in interferon-free hepatitis C therapy: 2014 and beyond
Authors: Souvik Sarkar, Joseph K. Lim
Journal: Hepatology (2014)

Background: Interferon-based treatment is not suitable for many patients with hepatitis C virus (HCV) infection because of contraindications such as psychiatric illness, and a high burden of adverse events. We assessed the efficacy and safety of an interferon-free regimen—a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir (400 mg) and the HCV NS5A inhibitor ledipasvir (90 mg), with and without ribavirin—in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen. Methods: For this open-label study, we enrolled 100 adult patients (>18 years) with HCV infection at a centre in the USA between Nov 2, 2012, and Dec 21, 2012. In cohort A, we used a computer-generated sequence to randomly assign (1:1:1; stratified by HCV genotype [1a vs 1b]) 60 non-cirrhotic, treatment-naive patients to receive sofosbuvir plus ledipasvir for 8 weeks (group 1), sofosbuvir plus ledipasvir and ribavirin for 8 weeks (group 2), or sofosbuvir plus ledipasvir for 12 weeks (group 3). In cohort B, we randomly allocated (1:1; stratified by genotype and presence or absence of cirrhosis) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive sofosbuvir plus ledipasvir for 12 weeks (group 4) or sofosbuvir plus ledipasvir and ribavirin for 12 weeks (group 5). 22 (55%) of 40 patients in cohort B had compensated cirrhosis. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01329978. Results: In cohort A, SVR12 was achieved by 19 (95%) of 20 patients (95% CI 75-100) in group 1, by 21 (100%) of 21 patients (84-100) in group 2, and by 18 (95%) of 19 patients (74-100) in group 3. In cohort B, SVR12 was achieved by 18 (95%) of 19 patients (74-100) in group 4 and by all 21 (100%) of 21 patients (84-100) in group 5. Two patients had viral relapse; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment. The most common adverse events were nausea, anaemia, upper respiratory tract infection, and headache. One patient in group five had a serious adverse event of anaemia, thought to be related to ribavirin treatment. Interpretation: These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV, irrespective of treatment history or the presence of compensated cirrhosis. Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin.
Interferon Regulatory Factor 6 (<i>IRF6</i>) Gene Variants and the Risk of Isolated Cleft Lip or Palate
Authors: Theresa M. Zucchero, Margaret E. Cooper, Brion S. Maher, Sandra Daack-Hirsch, Buena Nepomuceno, Lucilene Ribeiro, Diana Caprau, Kaare Christensen, Yasushi Suzuki, Junichiro Machida, Nagato Natsume, Koh-Ichiro Yoshiura, Alexandre R. Vieira, Ieda M. Orioli, Eduardo E. Castilla, Lina Moreno, Mauricio Arcos-Burgos, Andrew C. Lidral, L. Leigh Field, You-e Liu, Ajit Ray, Toby H. Goldstein, Rebecca E. Schultz, Min Shi, Marla K. Johnson, Shinji Kondo, Brian C. Schutte, Mary L. Marazita, Jeffrey C. Murray
Journal: New England Journal of Medicine (2004)

Cleft lip or palate (or the two in combination) is a common birth defect that results from a mixture of genetic and environmental factors. We searched for a specific genetic factor contributing to this complex trait by examining large numbers of affected patients and families and evaluating a specific candidate gene.We identified the gene that encodes interferon regulatory factor 6 (IRF6) as a candidate gene on the basis of its involvement in an autosomal dominant form of cleft lip and palate, Van der Woude's syndrome. A single-nucleotide polymorphism in this gene results in either a valine or an isoleucine at amino acid position 274 (V274I). We carried out transmission-disequilibrium testing for V274I in 8003 individual subjects in 1968 families derived from 10 populations with ancestry in Asia, Europe, and South America, haplotype and linkage analyses, and case-control analyses, and determined the risk of cleft lip or palate that is associated with genetic variation in IRF6.Strong evidence of overtransmission of the valine (V) allele was found in the entire population data set (P<10(-9)); moreover, the results for some individual populations from South America and Asia were highly significant. Variation at IRF6 was responsible for 12 percent of the genetic contribution to cleft lip or palate and tripled the risk of recurrence in families that had already had one affected child.DNA-sequence variants associated with IRF6 are major contributors to cleft lip, with or without cleft palate. The contribution of variants in single genes to cleft lip or palate is an important consideration in genetic counseling.
Pfizer found guilty of breaching code
Authors: Tony Sheldon
Journal: BMJ (2005)

Pharmaceutical company Pfizer has been ordered to shut down a Dutch website about erectile dysfunction that it sponsors, after a complaint was upheld that it was guilty of the “unlawful public advertising” of its prescription only drug sildenafil (Viagra).

Dutch MP Agnes Kant brought a complaint after a series of radio commercials from Pfizer last October on erectile dysfunction.

Although Dutch law permits “symptom advertising”—which draws attention to specific medical conditions but does not name pharmaceutical …
Carcinoid tumour of the ampulla of Vater presenting as acute pancreatitis.
Authors: J M Dixon, R W Chapman, A R Berry
Journal: Gut (1987)

The first report of a carcinoid tumour of the ampulla of Vater causing acute pancreatitis is presented. The pancreatitis resulted from ampullary obstruction and diversion of the bile through the pancreas. Endoscopic retrograde cholangiopancreatography established the correct diagnosis, making this the first occasion in which a carcinoid tumour of the ampulla of Vater has been correctly diagnosed before surgery.
New Chains for Prometheus
Authors: Samuel Vaisrub
Journal: JAMA (1974)

Medicine is under attack from many directions. Weapons range from barbs of innuendo and vituperation, aimed at the individual physicians, to cannonballs targeted on medical institutions. Practicing physicians are accused of venality, of catering to the rich while neglecting the poor. Medical research scientists are criticized for callousness to the suffering of experimental animals. Clinical investigators are reprimanded for disregarding human rights. The profession as a whole is taken to task for opposing socialized medicine, for willfully restricting its numbers and, above all, for playing God in making decisions on matters involving religious, moral, and philosophical considerations. All too familiar, these and other accusations, pointing to medicine's actual or alleged shortcomings, may provoke resentment, contrition, doubt, or indignation. The response will depend largely on the individual physician's assessment of how his performance measures up to the ideals of medicine. But what will the response be to an attack on these
International Nomenclature cosmetic ingredient awareness in Scotland
Authors: C.J. Fleming, J.L. Bong, A. Forsyth
Journal: British Journal of Dermatology (1999)

Journal Article International Nomenclature cosmetic ingredient awareness in Scotland Get access C.J. Fleming, C.J. Fleming Contact Dermatitis Investigation Unit, Glasgow Royal Infirmary, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.L. Bong, J.L. Bong Department of Dermatology, Western Infirmary, Glasgow, U.K. Dr Jan L.Bong, Department of Dermatology, Western Infirmary, 56 Dumbarton Road, Glasgow G11 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. Forsyth A. Forsyth Contact Dermatitis Investigation Unit, Glasgow Royal Infirmary, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 5, 1 November 1999, Pages 880–881, https://doi.org/10.1046/j.1365-2133.1999.03173.x Published: 01 November 1999
Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals
Authors: Carolina Riveros, Agnes Dechartres, Elodie Perrodeau, Romana Haneef, Isabelle Boutron, Philippe Ravaud
Journal: PLoS Medicine (2013)

Agnes Dechartres and colleagues searched ClinicalTrials.gov for completed drug RCTs with results reported and then searched for corresponding studies in PubMed to evaluate timeliness and completeness of reporting. Please see later in the article for the Editors' Summary
Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease.
Authors: B K Kilhovd, T J Berg, K I Birkeland, P Thorsby, K F Hanssen
Journal: Diabetes Care (1999)

OBJECTIVE: To investigate whether serum levels of advanced glycation end products (AGEs) and the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) are increased in patients with type 2 diabetes compared with nondiabetic control subjects and whether levels of AGEs and/or CML differ in patients with type 2 diabetes with or without coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Serum levels of AGEs and CML were measured with an immunoassay in 32 men and 21 women aged 59.3+/-6.2 years (means +/- SD) with type 2 diabetes for 7.3 + 3.1 years and in 17 men and 17 women aged 56.2+/-4.2 years without diabetes. Of the patients with diabetes, 18 had CHD. RESULTS: The serum levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects (median [5th-95th percentile]: AGEs 7.4 [4.4-10.9] vs. 4.2 [1.6-6.4] U/ml, P &amp;lt; 0.0001; CML 15.6 [5.6-29.9] vs. 8.6 [4.4-25.9] U/ml, P &amp;lt; 0.0001). The median level of AGEs but not CML was significantly increased in patients with type 2 diabetes and CHD compared with patients without CHD (8.1 [6.4-10.9] vs. 7.1 [3.5-9.8] U/ml, P = 0.03). There were significant positive correlations between serum levels of AGEs and CML in both patients and control subjects. CONCLUSIONS: Levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects, and levels of AGEs but not CML were significantly higher in patients with type 2 diabetes and CHD than in patients without diabetes. These results may indicate a role for non-CML AGEs in the development of macrovascular disease in patients with type 2 diabetes.
Anti-doping Controls
Authors: A. Dirix
Journal: British Journal of Sports Medicine (1980)

A study was carried out on the effect of endurance training on the plasma catecholamine response to exercise at the same submaximal workload and to short duration, all out exercise.Eight experienced swimmers (six men and two women; average age 18 years), who had not trained for 2-7 months, swam 200 yards on one day and 1000 yards the next, both as fast as possible.After nine weeks of vigorous training the same tests were performed, the 200 yards flat out but the 1000 yards at the same pace as the initial test.After training, resting heart rates were significantly lower and in the 1000 yard swim heart rate response was 15% lower than pre-training figures though responses were similar for the 200 yard swims.In the 200 yard swim plasma insulin and glucagon concentrations were not significantly altered either prior to or after training.However the 1000 yard swim produced a decrease in insulin level and an increase in glucagon level both before and after training.Adrenaline and noradrenaline concentrations, on average, were greatly increased after the 200 yard swim.Both levels also rose considerably after training, but the increase in adrenaline concentration was significantly smaller than before training.Both plasma catecholamines were significantly increased by the 1000 yard swim but post-exercise adrenaline levels were only one-ninth and noradrenaline only one-third as high after training.These results suggest that the catecholamine effect on the endocrine pancreas may be moderated by other factors.It also seems clear that during short-term, high intensity swimming, glucagon does not play an important role in stimulation of liver glycogenolysis or gluconeogenesis.
Psychiatric Symptoms in Community, Clinic, and Mental Hospital Groups
Authors: BRUCE P. DOHRENWEND, DEWITT L. CRANDELL
Journal: American Journal of Psychiatry (1970)

Do large proportions of the general population show psychiatric symptomatology resembling that seen in psychiatric patients? Responses by 248 adult leader, community sample, and patient subjects in Washington Heights. New York City, to questions about 46 symptoms show that quantitative resemblance exists. This resemblance is due mainly, however, to the high frequency of less serious symptoms in the nonpatient groups. Moreover, regardless of clinicians' ratings of severity, the particular symptoms tended to be judged less serious by those who reported them in nonpatient than in patient groups.