tbuckley/cabot-search huggingface dataset:
1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system
Authors: Yan Chun Li, Juan Kong, Minjie Wei, Zhou-Feng Chen, Shu Q. Liu, Li-Ping Cao
Journal: Journal of Clinical Investigation (2002)

Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D(3) markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D(3) is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension.
Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite
Authors: S. Baris, A. Kiykim, A. Ozen, A. Tulunay, E. Karakoc-Aydiner, I. B. Barlan
Journal: Allergy (2013)

Background We aimed to investigate the efficacy, safety, and T regulatory cell response of vitamin D as an adjunct to allergen-specific immunotherapy (IT). Methods Fifty children with asthma and receiving pharmacotherapy were randomized into three groups as: subcutaneous IT (SCIT) along with vitamin D supplementation (650 U/day; n: 17), SCIT alone (n: 15), and pharmacotherapy alone (n: 18). All patients were evaluated at baseline, 6th and 12th months for scorings of symptoms and medication, skin prick testing, total IgE, specific IgE, and Der p 1-specific IgG4. In addition, D. pteronyssinus-induced CD4+CD25+FOXP3+T regulatory cell percentage, intracellular Foxp3 expression, and peripheral blood mononuclear cell IL-10 and TGF-β responses were assessed. Results In the SCIT + vitamin D and SCIT alone groups, total asthma symptom score (TASS), total symptom score (TSS), and total medication scores (TMS) were significantly lower than pharmacotherapy group at the end of 1 year. While the comparison of delta values (Δ 6th and Δ 12th month − baseline) of those scores revealed no significant differences between the two IT groups, TASS at the 6th month was lower in the SCIT + vitamin D group compared with others. There was a significant and positive trend in the levels of Der p 1-specific IgG4 in both IT groups throughout the study period. Whereas the levels of Der p 1-induced IL-10 and TGF-β were similar between IT groups, the mean fluorescence intensity of Foxp3 was highest in the SCIT + vitamin D group compared with others at the 12th month. The rate of discontinuation of inhaled corticosteroid (ICS) was 6/17 in SCIT + vitamin D, 3/15 in SCIT, and 0/18 in the pharmacotherapy group (P = 0.02). Conclusion Both SCIT groups fared better than pharmacotherapy alone at the end of 1 year. Although the clinical and immunologic outcomes were mostly similar between the two IT groups, some favorable outcomes of vitamin D warrant further investigation in more selected populations with varying doses as adjunct to IT.
DNA Damage–Induced Cytotoxicity Is Dissociated from BRCA1's DNA Repair Function but Is Dependent on Its Cytosolic Accumulation
Authors: Hong Wang, Eddy S. Yang, Juhong Jiang, Somaira Nowsheen, Fen Xia
Journal: Cancer Research (2010)

The tumor suppressor BRCA1 is a nuclear shuttling protein. However, the role of BRCA1 localization in the control of its functions remains to be elucidated. Given the central role of BRCA1 in DNA damage repair, we hypothesized that depletion of nuclear BRCA1 would compromise its nuclear function in DNA repair and thereby result in enhanced cytotoxic response to DNA damage. In this study, we showed that repair of DNA double-strand breaks required BRCA1 in the nucleus. In addition, sequestering BRCA1 in the cytosol enhanced the cytotoxic response to ionizing radiation or cisplatin in human breast and colon cancer cells. However, further genetic dissection of the mechanism of this enhanced cytotoxicity using BRCA1 mutants deficient in double-strand break repair unexpectedly revealed a dissociation of BRCA1's function in DNA repair from its effects on cellular sensitivity to DNA damage. Interestingly, we observed a dependence of the DNA damage-induced cell killing on the translocation and accumulation of BRCA1 in the cytosol. Together, these data suggest a novel role of cytoplasmic translocation of BRCA1, not only in controlling its DNA repair functions, but also in the regulation of cell death processes following DNA damage. Further dissection of the mechanism of cytotoxicity induced by BRCA1 cytoplasmic translocation revealed the involvement of the apoptotic pathway. We propose that the status of BRCA1 nuclear/cytoplasmic shuttling might provide a molecular marker to predict tumor response and a potential novel target to sensitize cancer cells to DNA damage-based therapy.
Factor XIII expression in the skin: Observations and a hypothesis
Authors: Neal S. Penneys
Journal: Journal of the American Academy of Dermatology (1990)

Factor XIII, a transglutaminase whose best-known function is in the coagulation cascade, is widely distributed in tissues. Three patterns of expression are found in the skin: (1) in cells in an angiocentric pattern around superficial vessels, (2) in early reparative lesions that result in fibroplasia, and (3) in certain sessile neoplasms. Around superficial vessels factor XIII probably stabilizes fibrin clots and helps to seal superficial wounds. On the basis of patterns of expression in evolving reparative lesions, factor XIII likely has an important but still undefined function in the development of fibroplasia. Factor XIII's proposed role in the promulgation of fibroplasia would be integral to the production of the stromal component of small neoplasms that is known to be associated with factor XIII expression.
SENSITIVITY OF SERUM ENZYME INHIBITORS TO A VARIETY OF CANCER CHEMOTHERAPEUTIC AGENTS 12
Authors: Frank W. Ellis, Philip M. West
Journal: Journal of Clinical Investigation (1951)

(Figuire 1)A 28-year-old Mexican male was admitted to the hos- pital with complaints of fullness in the left upper quad- rant for eight months, anorexia, weakness, fatigue, and 20 pounds weight loss of two months duration.Abnormal physical findings included pallor, enlarged spleen
Estrogen Receptor Genotypes and Haplotypes Associated with Breast Cancer Risk
Authors: Bert Gold, Francis Kalush, Julie Bergeron, Kevin Scott, Nandita Mitra, Kelly Wilson, Nathan Ellis, Helen Huang, Michael Chen, Ross Lippert, Bjarni V. Halldorsson, Beth Woodworth, Thomas White, Andrew G. Clark, Fritz F. Parl, Samuel Broder, Michael Dean, Kenneth Offit
Journal: Cancer Research (2004)

Abstract Nearly one in eight US women will develop breast cancer in their lifetime. Most breast cancer is not associated with a hereditary syndrome, occurs in postmenopausal women, and is estrogen and progesterone receptor-positive. Estrogen exposure is an epidemiologic risk factor for breast cancer and estrogen is a potent mammary mitogen. We studied single nucleotide polymorphisms (SNPs) in estrogen receptors in 615 healthy subjects and 1011 individuals with histologically confirmed breast cancer, all from New York City. We analyzed 13 SNPs in the progesterone receptor gene (PGR), 17 SNPs in estrogen receptor 1 gene (ESR1), and 8 SNPs in the estrogen receptor 2 gene (ESR2). We observed three common haplotypes in ESR1 that were associated with a decreased risk for breast cancer [odds ratio (OR), ∼ O.4; 95% confidence interval (CI), 0.2–0.8; P &amp;lt; 0.01]. Another haplotype was associated with an increased risk of breast cancer (OR, 2.1; 95% CI, 1.2–3.8; P &amp;lt; 0.05). A unique risk haplotype was present in ∼7% of older Ashkenazi Jewish study subjects (OR, 1.7; 95% CI, 1.2–2.4; P &amp;lt; 0.003). We narrowed the ESR1 risk haplotypes to the promoter region and first exon. We define several other haplotypes in Ashkenazi Jews in both ESR1 and ESR2 that may elevate susceptibility to breast cancer. In contrast, we found no association between any PGR variant or haplotype and breast cancer. Genetic epidemiology study replication and functional assays of the haplotypes should permit a better understanding of the role of steroid receptor genetic variants and breast cancer risk.
Percutaneous Therapy for Valvular Heart Disease
Authors: Blase A. Carabello
Journal: Circulation (2010)

I n this week's Circulation, Webb and colleagues 1 report on the use of percutaneous "valve-in-valve" rereplacement in the treatment of 24 ill patients with prosthetic valve failure under compassionate-use protocols.Ten procedures addressed the aortic valve; 7, the mitral valve; 6, the pulmonary valve; and 1, the tricuspid valve.The 30-day survival rate was 96%.Clinically, the results were excellent, with 88% of these highly symptomatic patients returning to New York Heart Association class I or II.Hemodynamically, the results were more modest, with an average postprocedure transaortic gradient of 20 mm Hg and a transmitral gradient of 8 mm Hg.
Role of surgery for optic pathway/hypothalamic astrocytomas in children
Authors: Yutaka Sawamura, Kyousuke Kamada, Yuuta Kamoshima, Shigeru Yamaguchi, Toshihiro Tajima, Junko Tsubaki, Takamitsu Fujimaki
Journal: Neuro-Oncology (2008)

Optic pathway/hypothalamic pilocytic astrocytomas in children are usually treated with chemotherapy following a surgical biopsy. In this report, we retrospectively considered the role of surgical intervention. In a series of 25 patients without neurofibromatosis type 1, the median age at initial treatment was 3.1 years (range, 0-15 years). Twenty cases were verified by histology, and five cases were diagnosed by MRI findings. Twenty-three patients received chemotherapy. All patients were alive at median follow-up of 66 months. Aims of surgery at the initiation of treatment were biopsy in 12 cases (1 stereotactic and 11 craniotomies) and debulking in 7 cases. The 11 open biopsies revealed pilocytic astrocytoma; however, noticeable complications occurred in five children after the biopsies. Review of preoperative MRIs showed that all had typical findings indicating pilocytic astrocytoma. The open biopsy offered no noteworthy benefit for the patients despite surgical risk and delay of chemotherapy. The extent of the seven resection surgeries was 70% or less removal, and postoperative adjuvant therapy was needed for six of the seven patients. The remaining six children who did not undergo surgery obtained remission with chemotherapy alone. After relapse in nine patients, 15 bulk-reduction surgeries were performed. Surgical resection was not curative in any patient. In five patients, mostly older children, cystic expansion of tumor was partially resected, resulting in additional remission. In conclusion, considering the risk of open surgery and the effectiveness of chemotherapy, the role of surgical intervention is restricted to bulk-reduction surgery only when it is inevitable, especially at relapse after chemotherapy.
Malignant Peripheral Nerve Sheath Tumor in Neurofibromatosis Type 1
Authors: John P. Rossiter, Paul V. Fenton
Journal: JAMA Neurology (2013)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
How Good Is “Evidence” from Clinical Studies of Drug Effects and Why Might Such Evidence Fail in the Prediction of the Clinical Utility of Drugs?
Authors: Huseyin Naci, John P.A. Ioannidis
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.
Inflammation in ankylosing spondylitis: a systematic description of the extent and frequency of acute spinal changes using magnetic resonance imaging
Authors: X Baraliakos
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Magnetic resonance imaging (MRI) is increasingly used to detect inflammation in the spine of patients with ankylosing spondylitis (AS). <b>Objectives:</b> To detect differentially the presence and extent of inflammation in the three spinal segments of patients with AS by MRI. <b>Methods:</b> In 38 patients with active AS, acute spinal lesions were assessed by T<sub>1</sub> weighted, gadolinium enhanced, spin echo MRI (T<sub>1</sub>/Gd-DTPA) and short τ inversion recovery (STIR) sequences. MRI was quantified by the validated scoring system ASspiMRI-a. Acute spinal lesions were detected in the whole spine and in each spinal segment. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebral body. <b>Results:</b> A greater number of inflammatory spinal lesions were found by the STIR sequence than by Gd-DTPA: inflammation was present in 30.6% of the VUs as assessed by STIR, compared with 26.8% of the same VUs assessed by T<sub>1</sub>/Gd-DTPA. Inflammation was found more commonly in the thoracic spine (TS) than in the cervical (CS) or the lumbar spine (LS) with both techniques. When STIR was used, spinal inflammation in the CS, the TS, and LS was detected in 10/38 (26%), 28/38 (74%), and 9/38 (24%) patients, respectively. The VU T7/8 was found to be the VU most often affected by both techniques (27.8% by T<sub>1</sub>/Gd-DTPA and 34.5% by STIR). <b>Conclusions:</b> Spinal inflammation is a common manifestation in patients with AS, and appears more frequently in the TS. The scoring system ASspiMRI-a can be used for evaluation of acute spinal changes in AS.
Prevalence of theHOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes
Authors: Z. Kote-Jarai, C. Mikropoulos, D.A. Leongamornlert, T. Dadaev, M. Tymrakiewicz, E.J. Saunders, M. Jones, S. Jugurnauth-Little, K. Govindasami, M. Guy, F.C. Hamdy, J.L. Donovan, D.E. Neal, J.A. Lane, D. Dearnaley, R.A. Wilkinson, E.J. Sawyer, A. Morgan, A.C. Antoniou, R.A. Eeles, Per Hall, Andrew Berchuck, Joe Dennis, Alison M. Dunning, Andrew Lee, Ed Dicks, Jacques Simard, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissière, Frederic Robidoux, Stig E. Bojesen, Sune F. Nielsen, Borge G. Nordestgaard
Journal: Annals of Oncology (2015)
NSAID TREATMENT IS ASSOCIATED WITH PERSISTENTLY INCREASED RISK OF DEATH IN PATIENTS WITH PRIOR MYOCARDIAL INFARCTION: A NATIONWIDE STUDY
Authors: Anne-Marie Schjerning Olsen, Emil L. Fosbøl, Jesper Lindhardsen, Fredrik Folke, Mette Charlot, Jonas B. Olesen, Peter R. Hansen, Lars Køber, Christian Torp-Pedersen, Gunnar H. Gislason
Journal: Journal of the American College of Cardiology (2011)
Non-Hodgkin's lymphoma arising in cryptogenic fibrosing alveolitis
Authors: T R Orchard, C D Eraut, A G Davison
Journal: Thorax (1998)

Abstract The case report is presented of a patient with longstanding cryptogenic fibrosing alveolitis who developed a high grade B cell non-Hodgkin’s lymphoma in an area of fibrosis. cryptogenic fibrosing alveolitisnon-Hodgkin’s lymphomabronchus associated lymphoid tissue (BALT)
Alcohol consumption in arthritic patients: clinical and laboratory studies.
Authors: A Bradlow, A.G Mowat
Journal: Annals of the Rheumatic Diseases (1985)

In popular belief patients with chronic arthritis take alcohol for its analgesic effect. To test this we studied by validated questionnaire the past and present alcohol consumption of 103 patients with primary osteoarthritis of the hip (OA), 95 patients with rheumatoid arthritis (RA), and 90 orthopaedic non-arthritic controls. OA men were most likely and RA men least likely to have been heavy drinkers at any time of their lives. Mean red corpuscular volume (MCV), gamma-glutamyltransferase (GGT), and serum uric acid (SUA) levels did not correlate with reported alcohol consumption. Two of 93 OA femoral heads examined had avascular change; both were from heavy drinkers. The abstemiousness of RA men compared with their OA counterparts was due to a striking increase in joint pain after drinking alcohol (p = 0.004), fear of adverse drug reactions with alcohol, and a widespread belief not expressed by OA men that 'alcohol and arthritis do not mix'.
The Impact of Health Insurance on Health
Authors: Helen Levy, David Meltzer
Journal: Annual Review of Public Health (2007)

How does health insurance affect health? After reviewing the evidence on this question, we reach three conclusions. First, many of the studies claiming to show a causal effect of health insurance on health do not do so convincingly because the observed correlation between insurance and good health may be driven by other, unobservable factors. Second, convincing evidence demonstrates that health insurance can improve health measures of some population subgroups, some of which, although not all, are the same subgroups that would be the likely targets of coverage expansion policies. Third, for policy purposes we need to know whether the results of these studies generalize. Solid answers to the multitude of important questions about how specific health insurance policy options may affect health seem likely to be forthcoming only with investment of substantial resources in social experiments.
Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer
Authors: Jarle Bruun, Matthias Kolberg, Terje C. Ahlquist, Ellen C. Røyrvik, Torfinn Nome, Edward Leithe, Guro E. Lind, Marianne A. Merok, Torleiv O. Rognum, Geir Bjørkøy, Terje Johansen, Annika Lindblom, Xiao-Feng Sun, Aud Svindland, Knut Liestøl, Arild Nesbakken, Rolf I. Skotheim, Ragnhild A. Lothe
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis. Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903). Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 5′ UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical high-risk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (&amp;gt;75 years), stage II patients, and those with rectal cancer. Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. Clin Cancer Res; 21(16); 3759–70. ©2015 AACR.
Pathophysiological Role of Cytokines in Congestive Heart Failure
Authors: Arnon Blum, Hylton Miller
Journal: Annual Review of Medicine (2001)

▪ Abstract Heart failure is a complex neurohumoral and inflammatory syndrome. Recent studies have shown that proinflammatory cytokines (interleukin-1, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor) are involved in cardiac depression and in the complex syndrome of heart failure. Understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure by the use of monoclonal antibodies directed against specific cytokines to block the downhill progression of heart failure.