tbuckley/cabot-search huggingface dataset:
Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation
Authors: Mi Wang, Hui Yang, Ling-Yun Zheng, Zheng Zhang, Yong-Bo Tang, Guan-Lei Wang, Yan-Hua Du, Xiao-Fei Lv, Jie Liu, Jia-Guo Zhou, Yong-Yuan Guan
Journal: Circulation (2012)

Background— The Ca 2+ -activated chloride channel (CaCC) plays an important role in a variety of physiological functions. In vascular smooth muscle cells, CaCC is involved in the regulation of agonist-stimulated contraction and myogenic tone. The physiological functions of CaCC in blood vessels are not fully revealed because of the lack of specific channel blockers and the uncertainty concerning its molecular identity. Methods and Results— Whole-cell patch-clamp studies showed that knockdown of TMEM16A but not bestrophin-3 attenuated CaCC currents in rat basilar smooth muscle cells. The activity of CaCC in basilar smooth muscle cells isolated from 2-kidney, 2-clip renohypertensive rats was decreased, and CaCC activity was negatively correlated with blood pressure (n=25; P &lt;0.0001) and medial cross-sectional area (n=24; P &lt;0.0001) in basilar artery during hypertension. Both upregulation of CaMKII activity and downregulation of TMEM16A expression contributed to the reduction of CaCC in the hypertensive basilar artery. Western blot results demonstrated that angiotensin II repressed TMEM16A expression in basilar smooth muscle cells (n=6; P &lt;0.01). Knockdown of TMEM16A facilitated and overexpression of TMEM16A inhibited angiotensin II–induced cell cycle transition and cell proliferation determined by flow cytometry and BrdU incorporation (n=6 in each group; P &lt;0.05). TMEM16A affected cell cycle progression mainly through regulating the expression of cyclin D1 and cyclin E. Conclusions— TMEM16A CaCC is a negative regulator of cell proliferation. Downregulation of CaCC may play an important role in hypertension-induced cerebrovascular remodeling, suggesting that modification of the activity of CaCC may be a novel therapeutic strategy for hypertension-associated cardiovascular diseases such as stroke.
FAT NECROSIS AT AN OBSCURE LOCATION
Authors: P. E. TRUESDALE
Journal: JAMA (1928)

To the surgeon, fat necrosis is a familiar pathologic reality. It is a pathognomonic sign of rapidly destructive changes in the pancreas. In appearance it takes the form of small opaque white areas which are signposts of impending danger from hemorrhagic necrosis or other forms of acute fulminating infection of the pancreas. The recognition of these small chalky spots during an operation, therefore, becomes a matter of vital importance. They may be present but not apparent. When few and widely scattered they may easily escape recognition, especially if one does not have them in mind. My object in this communication is to stress the importance of searching for fat necrosis in all cases of acute infection of the gallbladder and bile ducts, and to point out a concealed area where fat necrosis may be found before it appears on the peritoneum ordinarily limited within the surgeon's range of view. Chronic
NS5A inhibitors in the treatment of hepatitis C
Authors: Jean-Michel Pawlotsky
Journal: Journal of Hepatology (2013)

Hepatitis C virus infection is a major health problem worldwide and no vaccine has yet been developed against this virus. In addition, currently approved pharmacotherapies achieve suboptimal cure rates and have side effects that result in non-compliance and premature treatment discontinuation. Significant research has been devoted to developing direct-acting antiviral agents that inhibit key viral functions. In particular, several novel drug candidates that inhibit the viral non-structural protein 5A (NS5A) have been demonstrated to possess high potency, pan-genotypic activity, and a high barrier to resistance. Clinical trials using combination therapies containing NS5A inhibitors have reported results that promise high cure rates and raise the possibility of developing interferon-free, all-oral regimens.
Cutaneous Complications of Chronic Continuous Subcutaneous Insulin Infusion Therapy
Authors: Angel Pietri, Philip Raskin
Journal: Diabetes Care (1981)

The cutaneous complications that can develop with continuous subcutaneous insulin infusion constitutes a significant concern when using this innovative and highly effective form of treatment for type I diabetes. These complications are twofold, the first being infection with abscess formation at the infusion needle site. Proper hygiene and frequent changing of the infusion site are helpful and effective measures. The second complication is the development of local allergic skin reactions, again at the infusion needle site, even with highly purified pork insulin. These may subside after several weeks on their own but switching insulin preparations also may be helpful.
Subcutaneous Hematoma Detected on Tc-99m Pyrophosphate Muscle Imaging
Authors: WAN-YU LIN, CHIA-HUNG KAO, SHYH-JEN WANG
Journal: Clinical Nuclear Medicine (1998)

A 30-year-old man had two subcutaneous hematomas in the left buttock and the right back after blunt trauma in a car accident. These two subcutaneous hematomas were demonstrated clearly by Tc-99m pyrophosphate muscle imaging.
WEIGHT LOSS PREDICTS MORTALITY INDEPENDENT OF BASELINE BODY MASS INDEX AMONG PATIENTS WITH CORONARY HEART DISEASE
Authors: Aziza Azimi, Christian Torp-Pedersen, Gunnar Gislason, Peter Riis Hansen, Per Foege Jensen, Per Thayssen, Hans-Henrik Tilsted, Leif Thuesen, Mette Gitz Charlot
Journal: Journal of the American College of Cardiology (2013)
Mikulicz Disease and Lupus Erythematosus
Authors: C. Jack Bark
Journal: JAMA (1977)

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
Modulation of established murine collagen-induced arthritis by a single inoculation of short-term lipopolysaccharide-stimulated dendritic cells
Authors: L Salazar, O Aravena, P Abello, A Escobar, J Contreras-Levicoy, N Rojas-Colonelli, D Catalan, A Aguirre, R Zuniga, B Pesce, C Gonzalez, R Cepeda, M Cuchacovich, M C Molina, F Salazar-Onfray, M Delgado, R E Toes, J C Aguillon
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> The use of regulatory or immature dendritic cells (DCs) as tools for modulating experimental rheumatoid arthritis is very recent. Tumour necrosis factor (TNF)-stimulated DCs have been shown to restore tolerance in experimental autoimmune encephalomyelitis and collagen-induced arthritis (CIA). <h3>Objective:</h3> We investigated the capacity of short-term lipopolysaccharide (LPS)-stimulated DCs pulsed with type II collagen (CII) to induce tolerance against established CIA. <h3>Methods:</h3> Bone marrow-derived DCs were generated in the presence of granulocyte monocyte colony-stimulating factor (GM-CSF). After CIA induction, mice were injected at day 35 with a single dose of 4- or 24-h LPS-stimulated DCs that had been loaded with CII (4hLPS/CII/DCs or 24hLPS/CII/DCs). Arthritis progression was monitored by clinical and histological evaluations. <h3>Results:</h3> Flow cytometry of 4hLPS/CII/DCs showed intermediate CD40 and CD86 expression, lower than that of 24hLPS/CII/DCs (fully mature) and higher than that of CII/DCs (immature). A functional assay showed that 4hLPS/CII/DCs display increased endocytosis ability with respect to 24hLPS/CII/DCs, indicating a semimature state. The single inoculation of 4hLPS/CII/DCs in mice with established CIA reduced disease severity significantly over time. Histological evaluation of mice treated with 4hLPS/CII/DCs revealed diminished inflammatory synovitis, cartilage damage and fibrosis. Co-cultures of DCs with splenocytes from CIA mice showed that collagen-specific interferon (IFN)γ production was dramatically inhibited by 4hLPS/CII/DCs. 4hLPS/CII/DCs were high IL10 producers, which could explain the inhibition of arthritis progression in mice receiving this treatment because neither antibodies nor regulatory CD4+CD25+Foxp3+ T lymphocytes were demonstrated to be involved. <h3>Conclusion:</h3> Short-term LPS-modulated DCs inoculation interferes with CIA progression when loaded with CII.
Refractory period during provocation with eucapnic hyperventilation and methacholine.
Authors: K M Hurwitz, J M Roach, G J Argyros, A H Eliasson, Y Y Phillips
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Eucapnic voluntary hyperventilation (EVH) and methacholine inhalation challenge (MIC) both cause bronchoconstriction in asthmatics. A refractory period, or time when the response to bronchoprovocation in a series of challenges is diminished, has been found after hyperventilation or exercise but not after MIC. We investigated whether EVH or MIC blunted the response to the other test. Sixteen asthmatics were studied on 2 d, taking both tests each day. They were randomized to either EVH or MIC first on Day 1, then the opposite order on Day 2, 6 to 14 d apart. After EVH as a first test, the mean decline in FEV1 from baseline was 18.66 +/- 4.76% (mean +/- SEM), but when EVH followed MIC, the response to EVH was reduced by 30%, to a decline in FEV1 of only 13.02 +/- 3.75% (p = 0.0026). During MIC, the mean provocation dose to cause 20% decrease in FEV1 (PD20) given as the initial challenge was 54.77 +/- 21.60 breath units, compared with 46.94 +/- 19.55 breath units when MIC followed EVH (p = 0.54). However, the subset of patients most sensitive to methacholine (PD20 < 0.1 breath unit) had changes suggestive of a refractory period after EVH, with a mean increase in the PD20 from 0.06 +/- 0.01 to 3.35 +/- 1.43 (p = 0.069). Our data show that MIC attenuates the response to subsequent challenge with EVH. Conversely, EVH may only affect subsequent MIC in those most sensitive to methacholine.
Zinc deficiency: what are the most appropriate interventions?
Authors: Roger Shrimpton, Rainer Gross, Ian Darnton-Hill, Mark Young
Journal: BMJ (2005)

<h3>Background</h3> Detection of acute and prevalent HIV infection using point-of-care nucleic acid amplification testing (POC-NAAT) among outpatients with symptoms compatible with acute HIV is critical to HIV prevention, but it is not clear if it is cost-effective compared with existing HIV testing strategies. <h3>Methods</h3> We developed and parametrised a decision tree to compare the cost-effectiveness of (1) provider-initiated testing and counselling (PITC) using rapid tests, the standard of care; (2) scaled-up provider-initiated testing and counselling (SU-PITC) in which all patients were tested with rapid tests unless they opted out; and (3) opt-out testing and counselling using POC-NAAT, which detects both acute and prevalent infection. The model-based analysis used data from the Tambua Mapema Plus randomised controlled trial of a POC-NAAT intervention in Kenya, supplemented with results from a stochastic, agent-based network model of HIV-1 transmission and data from published literature. The analysis was conducted from the perspective of the Kenyan government using a primary outcome of cost per disability-adjusted life-year (DALY) averted over a 10-year time horizon. <h3>Results</h3> After analysing the decision-analytical model, the average per patient cost of POC-NAAT was $214.9 compared with $173.6 for SU-PITC and $47.3 for PITC. The mean DALYs accumulated per patient for POC-NAAT were 0.160 compared with 0.176 for SU-PITC and 0.214 for PITC. In the incremental analysis, SU-PITC was eliminated due to extended dominance, and the incremental cost-effectiveness ratio (ICER) comparing POC-NAAT to PITC was $3098 per DALY averted. The ICER was sensitive to disability weights for HIV/AIDS and the costs of antiretroviral therapy. <h3>Conclusion</h3> POC-NAAT offered to adult outpatients in Kenya who present for care with symptoms compatible with AHI is cost-effective and should be considered for inclusion as the standard of HIV testing in this population. <h3>Trial registration number</h3> Tambua Mapema (“Discover Early”) Plus study (NCT03508908) conducted in Kenya (2017–2020) i.e., Post-results.
Boosting of tuberculin sensitivity among Southeast Asian refugees.
Authors: G M Cauthen, D E Snider, I M Onorato
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Following an initial negative Mantoux tuberculin skin test, a second test, given as soon as 1 wk later, has been shown to elicit markedly larger reactions (boosting) in 20 to 40% of refugees tested in the United States. We conducted a study to determine the explanation for this phenomenon. Using the Mantoux method of intradermal skin testing, 2,469 refugees from Southeast Asia were initially tested with tuberculin followed by sequential retesting 7 and/or 90 d later. They were also tested initially with nontuberculous mycobacterial antigens. A high proportion (35.5%) of Southeast Asian refugees had reactions (> or = 10 mm induration) to an initial tuberculin test, and 30.9% of the nonreactors exhibited boosting on a subsequent tuberculin test. Boosting, unlike reactivity to the initial tuberculin test, was not associated with exposure to a person with tuberculosis. However, boosting was associated with reactivity to nontuberculous mycobacterial antigens and a history of bacille Calmette-Guérin (BCG) vaccination. Boosting in this population is therefore attributable to environmental exposure to nontuberculous mycobacteria that are endemic in Southeast Asia or to BCG vaccination, rather than to remote infection with Mycobacterium tuberculosis. Sequential tuberculin screening and preventive therapy of persons with boosted reactions is not recommended as a tuberculosis prevention strategy in this population.
Histological and cytological evidence of viral infection and human papillomavirus type 16 DNA sequences in cervical intraepithelial neoplasia and normal tissue in the west of Scotland: evaluation of treatment policy
Authors: J B Murdoch, L J Cassidy, K Fletcher, J W Cordiner, J C M Macnab
Journal: BMJ (1988)

Biopsy samples from 27 patients referred to a colposcopy clinic in Glasgow for cervical abnormalities were assessed for the relations among colposcopic appearances, cytological and histological diagnosis, expression of papillomavirus antigen, and the presence of human papillomavirus (HPV) types 6, 11, 16, and 18 deoxyribonucleic acid (DNA) sequences. Specimens were from colposcopically abnormal areas of the transformation zone and from colposcopically apparently normal areas of the zone in the same patients (paired matched internal control tissue). All 27 women referred for abnormal smears had colposcopic abnormalities. HPV-16 or 18 DNA sequences were detected in 20 of the 27 colposcopically abnormal biopsy samples and 13 of the 27 paired normal samples. Twelve samples of colposcopically normal tissue contained histological evidence of viral infection but only four of these contained HPV DNA sequences. The other nine samples of colposcopically normal tissue which contained HPV DNA sequences were, however, histologically apparently normal. HPV-6 and 11 were not detected. Integration of the HPV-16 genome into the host chromosome was indicated in both cervical intraepithelial neoplasia and control tissues. In two thirds of the HPV DNA positive samples the histological grade was classed as normal, viral atypia, or cervical intraepithelial neoplasia grade 1. Papillomavirus antigen was detected in only six of the abnormal and three of the normal biopsy samples, and HPV DNA was detected in all of these. The detection of HPV DNA correlates well with a combination of histological and cytological evidence of viral infection (20 of 22 cases in this series). A poor correlation between the site on the cervix of histologically confirmed colposcopic abnormality and the presence of HPV DNA sequences implies that a cofactor other than HPV is required for preneoplastic disease to develop. A separate study in two further sets of biopsy samples examined the state of HPV DNA alone. The sets were (<i>a</i>) 43 samples from cervical intraepithelial neoplasia and nine external controls and (<i>b</i>) 155 samples from cervical intraepithelial neoplasia, cervical cancer, vulval intraepithelial neoplasia, and vulval cancer and external controls. HPV-11 was found in only two (4·7%) of the 43 specimens from cervical intraepithelial neoplasia, whereas HPV-16 was found in 90 (58%) of the other 155 specimens. These results also suggest that HPV subtype is subject to geographical location rather than being an indicator of severity of the lesion or of prognosis.
OSTEOMYELITIS OF THE ILIUM IN CHILDREN
Authors: CARL BEARSE
Journal: JAMA (1923)

While infection of the iliac bone is not common, it is far from rare. When it occurs in children, it is a particularly serious condition, because the diagnosis at first may be difficult. Since immediate prognosis, prevention of complications and shortening of convalescence depend on early treatment, early diagnosis is essential. This condition has been looked on as infrequent from such published reports as that of Monsaigeon,<sup>1</sup>who was able to compile only fourteen cases during a period of thirteen years in one of the large clinics in Paris, and of Simmons<sup>2</sup>who, in his report of ninety-seven cases of general osteomyelitis in the Massachusetts General Hospital, listed only two cases of ilium infection. In addition, at the German Surgical Congress,<sup>3</sup>Lücke reported twenty-four cases of osteomyelitis, including one of the ilium; Volkman, twenty-nine, including none of the ilium; Schede, twenty-four, including two; Kocher, thirty, including one;
Construct and longitudinal validity of a modified Huang clinical scoring system in adult cystic fibrosis patients
Authors: E Matouk, RH Ghezzo, J Gruber, R Hidvegi, K Gray-Donald
Journal: European Respiratory Journal (1999)

This study reports on the evaluation of a modified Huang scoring system in adult cystic fibrosis patients for construct and longitudinal validity. Two studies were performed. In the first study, the scoring system was applied to 59 adult cystic fibrosis patients prospectively followed at the Montreal Chest Institute. The total score and all the subscores distinguished between patients with the expected mild degree of disease severity seen in patients colonized with only Staphylococcus aureus, compared to the more advanced disease severity seen in patients colonized with Pseudomonas aeruginosa or multiple resistant pseudomonads. The relationship between disease severity assessed by forced expiratory volume in one second per cent predicted and the nonpulmonary function subscores was significant and linear (for the radiological subscore, r2=0.694, p<0.0001) and curvilinear (for the clinical and complications subscores, r2=0.622, p=0.0192 and r2=0.508, p=0.0009 respectively). In the second study, 20 patients retrospectively recorded were added to the prospective group. There was a good association between changes in nonpulmonary function subscores and changes in spirometry over a mean follow-up period of 779+/-204 days, at all levels of disease severity. The contribution of changes in clinical and complications subscores to the changes in total score became progressively more significant with more advanced disease severity. In conclusion, significant evidence for the construct validity of the scoring system as a discriminative instrument and for the longitudinal validity as an evaluative instrument was demonstrated. It may prove of value in assessing outcome of therapeutic interventions in clinical trials in patients with cystic fibrosis.
Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.
Authors: K B Pomerantz, A R Tall, S J Feinmark, P J Cannon
Journal: Circulation Research (1984)

We studied the effects of plasma high density and low density lipoproteins upon the synthesis of prostacyclin and prostaglandin E2 by vascular smooth muscle cells. Prostaglandin synthesis was measured in 24-hour cultures by radioimmunoassay of the stable metabolites of prostacyclin, 6-keto-prostaglandin F1 alpha and of prostaglandin E2. High density lipoproteins induced dose-dependent increases in the release of 6-keto-prostaglandin F1 alpha and of prostaglandin E2 from smooth muscle cells to values 14- and 50-fold above control. Incubations with low density lipoproteins at comparable cholesterol concentrations also induced dose-dependent release of 6-keto-prostaglandin F1 alpha and prostaglandin E2, but to a lesser extent. Rat high density lipoprotein, which contained 2.5 times more cholesteryl arachidonate than human high density lipoproteins, stimulated 6-keto-prostaglandin F1 alpha and prostaglandin E2 release 2- to 3-fold more than human high density lipoproteins, whereas the delipidated apoproteins of high density lipoproteins had no significant effect on prostaglandin synthesis. Recombinant high density lipoproteins containing cholesteryl-[1- 14C]arachidonate stimulated release of [14C]-6-keto-prostaglandin F1 alpha and [14C]prostaglandin E2 by smooth muscle cells. The ionophore, A 23187, released labeled 6-keto-prostaglandin F1 alpha and prostaglandin E2 from cells preincubated with recombinant high density lipoprotein containing cholesteryl-[1- 14C]arachidonate. Unlabeled high density lipoproteins, in contrast, did not cause release of radioactive prostaglandins from cells preincubated with [1- 14C]arachidonate. Phospholipase activators were synergistic (bradykinin) or additive (angiotensin II) with high density lipoprotein in stimulation of prostaglandin synthesis. The data indicate that both high and low density lipoproteins stimulate the synthesis of prostacyclin and prostaglandin E2 by vascular smooth muscle cells. The results suggest that the lipoproteins provide arachidonate to a phospholipase-sensitive pool accessible to cyclooxygenase.
Turkish doctors accuse police of deliberately injuring protesters
Authors: R. Hurley
Journal: BMJ (2013)

The Turkish Medical Association has called for an immediate end to “uncontrolled police violence,” saying that thousands of citizens have been injured in the past week after authorities used tear gas, water cannons, and plastic bullets to break up protests. The media have reported the deaths of at least three protesters.

The association’s call comes in response to several days of unrest in Turkish cities, including Istanbul, Ankara, and Izmir, after police responded violently to a protest against the redevelopment of a public park in the Taksim district of Istanbul.

On Friday 31 May riot police used tear gas against activists at Gezi Park, near Taksim Square. They had been protesting peacefully since 27 May against plans to build a shopping centre there. The …
Percutaneous Transvenous Melody Valve-in-Ring Procedure for Mitral Valve Replacement
Authors: Takashi Shuto, Norihiro Kondo, Yoav Dori, Kevin J. Koomalsingh, Andrew C. Glatz, Jonathan J. Rome, Joseph H. Gorman, Robert C. Gorman, Matthew J. Gillespie
Journal: Journal of the American College of Cardiology (2011)