tbuckley/cabot-search huggingface dataset:
The interactions of thiazide diuretics with parathyroid hormone and vitamin D
Authors: A. M. Parfitt
Journal: Journal of Clinical Investigation (1972)

In order to clarify the mechanisms of thiazide diuretic-induced hypocalciuria, the effect of a thiazide was studied for 7 days in seven patients with hypoparathyroidism on Vitamin D and one on calcium infusion, and seven euparathyroid patients with hypercalciuria. In the control group, calcium excretion (mg/24 hr) fell by 44% from 415 to 232 within 4 days and remained at this level. Plasma total calcium corrected for total protein did not change. In the hypoparathyroid group, calcium excretion fell by 11% from 351 to 311 and then returned to the base line level. Plasma total calcium (mg/100 ml) increased from 10.09 to 10.88, 11.29 and 10.77 at the end of the 2nd, 4th, and 7th day of thiazide administration. In the patient having i.v. calcium and no Vitamin D, neither plasma nor urinary calcium changed significantly. In both groups sodium excretion increased on the first 2 days and fell to or below base line level thereafter. Urinary phosphate, magnesium, and potassium increased, plasma phosphate rose, and magnesium and potassium fell. It is concluded that: (a) The hypocalciuric effect of thiazides requires the presence of parathyroid hormone and is not solely a result of sodium depletion. (b) The hypercalcemic effect of thiazides in hypoparathyroidism is due to increased release of calcium from bone and requires the presence of a pharmacologic dose of Vitamin D. (c) Thiazides enhane the action of parathyroid hormone on bone and kidney; Vitamin D can replace parathyroid hormone in this interaction in bone but not in kidney.
Hydroxamic Acid and Benzoic Acid–Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes <i>In Vitro</i> and <i>In Vivo</i>
Authors: Peibin Yue, Francisco Lopez-Tapia, David Paladino, Yifei Li, Chih-Hong Chen, Andrew T. Namanja, Tyvette Hilliard, Yuan Chen, Marcus A. Tius, James Turkson
Journal: Cancer Research (2015)

Abstract STAT3 offers an attractive target for cancer therapy, but small-molecule inhibitors with appealing pharmacologic properties have been elusive. Here, we report hydroxamic acid–based and benzoic acid–based inhibitors (SH5-07 and SH4-54, respectively) with robust bioactivity. Both inhibitors blocked STAT3 DNA-binding activity in vitro and in human glioma, breast, and prostate cancer cells and in v-Src–transformed murine fibroblasts. STAT3-dependent gene transcription was blocked along with Bcl-2, Bcl-xL, Mcl-1, cyclin D1, c-Myc, and survivin expression. Nuclear magnetic resonance analysis of STAT3-inhibitor complexes defined interactions with the SH2 and DNA-binding domains of STAT3. Ectopic expression of the SH2 domain in cells was sufficient to counter the STAT3-inhibitory effects of SH4-54. Neither compound appreciably affected STAT1 or STAT5 DNA-binding activities, STAT3-independent gene transcription, or activation of a panel of oncogenic kinases in malignant cells. Each compound decreased the proliferation and viability of glioma, breast, and prostate cancer cells and v-Src–transformed murine fibroblasts harboring constitutively active STAT3. Further, in mouse xenograft models of glioma and breast cancer, administration of SH5-07 or SH4-54 effectively inhibited tumor growth. Our results offer preclinical proof of concept for SH5-07 and SH4-54 as candidates for further development as cancer therapeutics. Cancer Res; 76(3); 652–63. ©2015 AACR.
Abstract P136: Relationships between Health Behaviors and Physical &amp; Mental Health among Smokers in California
Authors: Sarah E Linke, David R Strong, Steve Edland, Wael Al-Delaimy
Journal: Circulation (2014)

Background: Tobacco use, physical inactivity (PA), and sedentary behavior (SB) are leading behavioral risk factors for mental and physical health problems. The combination of smoking and other unhealthy lifestyle behaviors heightens the risk from smoking alone. Examining the relationships between health behaviors and health problems in a representative sample of California smokers enables quantification of the negative health effects of engaging in multiple unhealthy lifestyle behaviors over and above any adverse health effects from smoking alone. Methods: The 2011 California Longitudinal Smokers Survey (CLSS) surveyed smokers who participated in the previous 2009 California Health Interview Survey (CHIS), a population-based random sample of California residents. The present analyses included 1,718 current smokers surveyed again two years after participating in CHIS. The sample respondents were weighted to the age, gender, geographic place of residence, and ethnicity of the population of all adult California smokers. For the current analyses, physical inactivity was defined as &lt;10 minutes of sustained PA per week; a high level of SB was defined as ≥2 hours of leisure screen time per day; obesity was determined via calculated body mass index (BMI≥30) based on respondents’ self-reported height and weight; and elevated depressive and anxiety symptoms were determined via responses to two questions comprised of clusters of symptoms for each condition on the Patient Health Questionnaire for Depression and Anxiety (PHQ-4) instrument. Results: Results revealed a significant relationship between physical inactivity and obesity (t=3.5, p &lt; 0.001) and an interaction between sex and physical inactivity, such that male smokers who reported &lt;10 min/week of PA were more likely than male smokers who reported ≥10 min/week of PA to be obese (t=2.8, p&lt; 0.01). Physical inactivity was also associated with elevated anxiety symptoms among smokers (t=2.9, p&lt;0.01). Smokers who reported ≥2 hours/day of leisure time SB were more likely to report ever receiving a diagnosis of heart disease by a physician (t=3.3, p&lt;0.005). SB was also associated with elevated depressive symptoms among smokers (t=3.7, p&lt;0.001). Conclusion: The combination of smoking and physical inactivity or excessive SB is associated with worse mental and physical health than smoking alone. The American Heart Association encourages individuals to improve their cardiovascular health by quitting smoking, increasing PA, reducing SB, and maintaining a healthy weight. Public health efforts to increase awareness of the significant benefits of improving these and other health behaviors rely upon the collection, analysis, and publication of data demonstrating the associations between health behaviors and outcomes.
Multicenter Selective Lymphadenectomy Trial-I confirms the central role of sentinel node biopsy in contemporary melanoma management
Authors: M.B. Faries, A.J. Cochran, R.M. Elashoff, J.F. Thompson
Journal: British Journal of Dermatology (2015)

Sentinel lymph node (SLN) biopsy has become a standard procedure for many patients with melanoma and is recommended in numerous national and professional melanoma guidelines. The Multicenter Selective Lymphadenectomy Trial (MSLT‐1) confirms earlier large database studies and prospective clinical trials in demonstrating the independent and unequalled prognostic value of the SLN. It also demonstrates the ability of biopsy‐directed management to provide effective regional disease control with the least possible morbidity. These benefits are not in question and provide ample justification for the procedure, even without evidence of a survival benefit. However, MSLT‐1 also provides strong evidence of a substantial reduction in the risk of melanoma death for patients with intermediate thickness melanomas who harbour occult nodal metastases at the time of presentation. Denying appropriately selected patients with melanoma the opportunity to undergo SLN biopsy is no longer reasonable or acceptable.
Why did I become a doctor?: A wise headmaster
Authors: R H Salter
Journal: BMJ (2000)

biochemical analyses, confirming or refuting the inheritance of acute porphyria is not always possible.In these cases, genetic analysis is increasingly used, but this is sometimes difficult.In acute intermittent porphyria, for example, there are over 100 mutations including deletions, insertions, and missense, nonsense, and splicing mutations, and most of these mutations are family specific. 36However, the gene locations of many of the porphyrias have been identified, 1 11 and rapid progress is expected in this area.Clearly, families benefit when the mutation is detected.Not only will detection identify members with latent porphyria, but also unaffected members can be distinguished with confidence. 36Exclusion of carrier status makes it unnecessary to follow restrictions to prevent attacks and avoids the need for screening of future generations of that particular family branch.
Abstract P012: Short Leukocyte Telomere Length is Associated With Obesity in American Indians: The Strong Heart Family Study
Authors: Shufeng Chen, Jue Lin, Tet Matsuguchi, Elizabeth Blackburn, Elisa T Lee, Barbara V Howard, Jinying Zhao
Journal: Circulation (2014)

Background: Obesity is an independent risk factor for diabetes and cardiovascular disease. Telomere length shortens progressively with age, and shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders. However, the association between LTL and obesity has not been well established. Objective: To examine the association of LTL with obesity and related traits in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003), independent of known risk factors. Methods: A total of 3,162 participants (18-93 years old, 1,938 women) from 94 multigenerational families were included in this analysis. Obesity-related traits included body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio. LTL was measured by quantitative PCR. Association of LTL (continuous or in quintiles) with each adiposity index was examined using generalized linear mixed model, adjusting for age, sex, study center, education, lifestyle factors (current smoking, current drinking, physical activity, and total energy intake), hypertension (yes/no) and diabetes (yes/no). The association of LTL with prevalent obesity (BMI ≥30 kg/m2) was examined by multivariate logistic regression using the GLIMMIX procedure in SAS 9.3. Results: Prevalence of obesity was 59.6% (1,883 of 3,162). LTL was negatively correlated with age (r=-0.3, P&lt;0.0001). Obese participants had significantly shorter LTL than non-obese participants (age-adjusted P=0.0004). Multivariate regression analyses demonstrated that, LTL was significantly and inversely associated with all obesity indices (β= -2.68 [95% confidence interval (CI), -3.96 [[Unable to Display Character: &amp;#8210;]] -1.40] for BMI; -6.28 [95% CI, -9.29 [[Unable to Display Character: &amp;#8210;]] -3.27] for waist circumference; -3.95 [95% CI, -6.61 [[Unable to Display Character: &amp;#8210;]] -1.29] for hip circumference; and -0.02 [95% CI, -0.03 [[Unable to Display Character: &amp;#8210;]] -0.01] for waist-to-hip ratio). Participants with shorter LTL had significantly larger BMI (P trend across quintiles =0.0006), waist circumference (P trend =0.0005), hip circumference (P trend =0.01), and waist-to-hip ratio (P trend =0.002) compared to those with longer LTL. Multivariate-adjusted odds ratio (95% CI) for prevalent obesity was 1.32 (1.05-1.67), 1.29 (0.99-1.67), 1.29 (1.01-1.65) and 1.18 (0.89-1.57), respectively, for the 1st through 4th quintiles of LTL in comparison with the 5th quintile (P for trend =0.02). Excluding participants with diabetes and cardiovascular disease did not change our results. Conclusion: Shorter LTL was significantly associated with obesity and related measures in American Indians, independent of known risk factors. Our results may shed light on the complex pathophysiology of obesity and its related disorders.
CLINICAL EXPERIENCES WITH REDUCED DOSES OF THEVETIN ORALLY ADMINISTERED
Authors: Einar R. Daniels, William S. Middleton
Journal: Annals of Internal Medicine (1936)

Article1 October 1936CLINICAL EXPERIENCES WITH REDUCED DOSES OF THEVETIN ORALLY ADMINISTEREDEINAR R. DANIELS, M.D., WILLIAM S. MIDDLETON, M.D., F.A.C.P.EINAR R. DANIELS, M.D.Search for more papers by this author, WILLIAM S. MIDDLETON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-4-505 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptClinical studies of the action of thevetin1, 2 have amply confirmed the pharmacologic results of Chen and Chen3, 4 and established its reliable digitalis-like effect in man. The pulse is slowed, evidences of decompensation are alleviated, diuresis ensues and characteristic electrocardiographic changes occur when thevetin is given either by the oral or the parenteral route. Its untoward by-effects also parallel those of digitalis with a singular deviation in the gastrointestinal action. Here intestinal effects (cramps and diarrhea) in the main replace the common gastric upsets (anorexia, nausea and vomiting) incident to digitalis intoxication.The galenical preparations of the defatted be-still...References1. ARNOLDMIDDLETONCHEN HLWSKK: The action of thevetin, a cardiac glucoside, and its clinical application, Am. Jr. Med. Sci., 1935, clxxxix, 193. CrossrefGoogle Scholar2. MIDDLETONCHEN WSKK: Clinical results from oral administration of thevetin, a cardiac glucoside, Am. Heart Jr., 1936, xi, 75. CrossrefGoogle Scholar3. ChenChen KKAL: Similarity and dissimilarity of bufagins, bufotoxins, and digitaloid glucosides, Jr. Pharmacol, and Exper. Therap., 1933, xlix, 561. Google Scholar4. ChenChen KKAL: The action of crystalline thevetin, a cardiac glucoside of Thevetin neriifolia, Jr. Pharmacol, and Exper. Therap., 1934, li, 23. Google Scholar5. ChopraMukerjee RNB: The pharmacological action of " Thevetin "—a glucoside occurring in Thevetin neriifolia (Yellow Oleander), Indian Jr. Med. Research, 1933, xx, 903. Google Scholar6. Bastedo WA: Signs of overdosage in digitalis administration, Am. Pract., 1912, xlvi, 609. Google Scholar7. Shanahan WM: The results of digitalis administration in cardiac decompensation, Doctorate Thesis, University of Wisconsin, 1936. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Madison, Wisconsin*Received for publication July 21, 1936.From the Department of Medicine, University of Wisconsin. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1936Volume 10, Issue 4Page: 505-513KeywordsDiarrheaElectrocardiographyHeart rateIntoxicationNauseaVomiting Issue Published: 1 October 1936 PDF downloadLoading ...
Abstract 15709: Bivalirudin is Associated With Decreased Cardiovascular Outcomes and Bleeding as Compared to Heparin During PCI: A Meta- Analysis
Authors: Pawan Patel, Bhaskar Arora, Janos Molnar, Sandeep Khosla, Rohit Arora
Journal: Circulation (2014)

Background: Anticoagulant therapy is needed for safe and effective Percutaneous Coronary Intervention (PCI). Bivalirudin is widely used as an anticoagulant during PCI in acute coronary syndromes. Prior analysis had shown significant decrease in bleeding with similar rates of death with Bivalirudin compared to Heparin. Recent studies have shown mixed results. We performed this meta-analysis to compare the effect of bivalirudin versus heparin on major bleeding and deaths after PCI. Methods: We performed a systematic literature search for studies comparing bivalirudin versus heparin on major bleeding and deaths after PCI. Studies providing data on the outcome of major bleeding and deaths were included. Statistical heterogeneity across the various trials was tested using the Cochran’s Q statistic and I2 was computed to quantify heterogeneity. A two-sided alpha error of less than 0.05 was considered to be statistically significant (p &lt; 0.05). Results: Total of 22 eligible studies was included for major bleeding events and total 24 eligible studies were included for death events. The studies for major bleeding events were heterogeneous while studies for death events were homogenous; hence random and fixed effect model was used respectively to calculate combined relative risk (RR). Meta-analysis revealed that the use of bivalirudin compared to heparin is associated with statistically significant lower rates of major bleeding (RR, 0.612; CI, 0.504 to 0.742; p = 0.000) and death (RR, 0.709; CI, 0.606 to 0.830; p = 0.000). Conclusion: Our analysis concluded that bivalirudin compared to heparin is associated with lower rates of major bleeding and death during PCI.
Abstract P385: Physical Rehabilitation in Patients With Severe Heart Failure
Authors: Elena Kolesnikova, Gregory Arutyunov, Anna Rylova, Valentina Lobzeva
Journal: Circulation (2015)

Background: Physical exercises are very important as part of comprehensive cardiac rehabilitation(CR) for patients with heart failure (HF) due to increasing physical capacity and decreasing the number of pneumonias and hospitalizations but many protocols of physical exercises are not applicable for the patients with severe HF and lean body mass deficit (LBMD). Purpose: To study the possibility and efficacy of respiratory muscles trainings (RMT) in patients with NYHA class III-IV heart failure and LBMD. Methods: 56 patients 65,4±8,2 years old with NYHA III-IV HF with LBMD were randomized to either an exercise training group (EG)(28 pts) or to a control group (CG). The CG patients had standard drug therapy according to the European guidelines and nutrition with oligomeric nutrient mixtures. The EG participated additionally in a RMT with gradual increase of inspire and expire resistance. Trainings were held for 16 minutes twice a day for 12 months. Physical capacity by 6 minute walking test (6 MWT), lean bod...
104. A Novel Deletion in the FVIII B-Domain That Reduces Transgene Size While Preserving FVIII Activity
Authors: Peter W. Roelvink, David A. Suhy, Alexander A. Kolykhalov, Sara M. Cunningham, Taka Mizutani, Mark A. Kay
Journal: Molecular Therapy (2004)

Infection with the Hepatitis C virus (HCV) represents a major world-wide alth problem. RNAi based treatments have been proposed as a new therapeutic modality. We have focused on the expression of short-hairpin RNAs that can elicit an RNAi response against the HCV genome. We have used standard and custom algorithms to saturate regions of HCV sequences across multiple genotypes to locate optimal RNAi targets resulting in the identification of over 30 potential target sequences that will be evaluated for their efficacy. Because HCV does not replicate efficiently in cell culture or animal model systems, we have synthesized two independent HCV replicons, one of which is derived of patient material, which will be used as viral surrogates to quantify the degree of inhibition of viral replication in cells. Strategies which encompass the utilization of single or combinatorial short hairpin sequences are being compared in order to maximize the inhibition of viral replication as well as decrease the probability for the selection of escape mutants. To further this goal, we have designed novel expression cassettes that will lead to the expression (from bona-fide AAV gene therapy vectors) one or more short hairpin RNA sequences in vitro or in vivo. Taken together these new technologies represent a novel and robust method for the inhibition of HCV replication in cells and paves the way for a clinical trial for the use of RNAI in the treatment of HCV infection.
A Comprehensive Software Suite for the Analysis of cDNAs
Authors: Kazuharu Arakawa, Haruo Suzuki, Kosuke Fujishima, Kenji Fujimoto, Sho Ueda, Motomu Matsui, Masaru Tomita
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract We have developed a comprehensive software suite for bioinformatics research of cDNAs; it is aimed at rapid characterization of the features of genes and the proteins they code. Methods implemented include the detection of translation initiation and termination signals, statistical analysis of codon usage, comparative study of amino acid composition, comparative modeling of the structures of product proteins, prediction of alternative splice forms, and metabolic pathway reconstruction. The software package is freely available under the GNU General Public License at http://www.g-language.org/data/cdna/.
Inhibitory Effect of Isologous Irradiated Leukemic Extracts upon Spontaneous Leukemogenesis in AkR Mice
Authors: Raymond Latarjet
Journal: Cancer Research (1965)

Summary  Newborn AkR mice were given injections of an irradiated cell-free extract of isologous leukemic tissues. Litter mate controls were either not treated or treated similarly with an irradiated extract of isologous normal tissues. The injection was repeated at weekly intervals during 2 months. The animals were then kept under observation and their leukemias recorded. In all, 1947 mice were used.  The extracts were irradiated with ultraviolet light or with X-rays; the latter were used to observe either the direct or indirect effect of radiation. The following facts have been observed: ( a ) If the dose of radiation is high enough to suppress the superinfection effect of the extract, but does not exceed a certain limit, the irradiated extract of leukemic tissues decreases the frequency of the spontaneous leukemias. Extracts of normal tissues are ineffective. ( b ) Out of 5 ultraviolet-irradiated extracts, 1 was inactive, whereas the 4 others decreased the incidence of leukemia by 12–28%. ( c ) X-rayed extracts (indirect effect) were more effective, decreasing the incidence by 30–42%. ( d ) The direct effect of X-rays yields inactive extracts. The difference between the 2 modes of action of X-rays confirms  in vivo  what had been observed  in vitro  with the Rous sarcoma virus.  These results suggest a prospective scheme for an anti-viral treatment, complementary to the classical treatment of certain cancers.
Role of immunmodulators in allergen-specific immunotherapy
Authors: M. V. Kopp
Journal: Allergy (2011)

To cite this article: Kopp MV. Role of immunmodulators in allergen-specific immunotherapy. Allergy 2011; 66: 792–797. Allergen-specific immunotherapy (SIT) is the only causal treatment of allergic disorders and therefore a cornerstone in the management of respiratory allergy. SIT is effective in patients with allergic rhinitis and mild-to-moderate allergic asthma. Successful treatment is associated with decrease in allergic symptoms of the upper and lower airways. The most relevant limitation in the daily routine is the restricted use of SIT in patients with moderate-to-severe allergic asthma. A strategy to overcome this limitation is to combine SIT with immunmodulators. One example of a recently developed immunmodulator is Omalizumab, a humanized, monoclonal anti-IgE antibody that binds to circulating IgE molecules, thus interrupting the allergic cascade downstream the IgE production of B cells. Up to now, four clinical trials have been performed, which all showed that the combination of Omalizumab and SIT is safe and clinically more effective than SIT alone. Moreover, administration of Omalizumab prior to SIT reduces the risk of SIT-related systemic reactions. Omalizumab and SIT are also effective in patients with mild–moderate allergic asthma. In conclusion, the use of Omalizumab as an additive immunmodulator improves safety and efficacy and might be a useful approach to broaden the indication of specific immunotherapy in allergic patients.