tbuckley/cabot-search huggingface dataset:
Abstract 12737: Physiological Balance Between Nitric Oxide and Endothelium-Derived Hyperpolarizing Factor Plays a Crucial Role in Cardiovascular Homeostasis
Authors: Shigeo Godo, Hiroki Saito, Ayuko Sawada, Saori Sato, Shuhei Tanaka, Hiroaki Shimokawa
Journal: Circulation (2014)

Background: The endothelium modulates vascular tone by synthesizing and releasing endothelium-derived relaxing factors (EDRFs), including prostacyclin, nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHFs). The contribution of each EDRF to endothelium-dependent vasodilatation varies depending on the vessel size; conduit arteries are primarily regulated by NO and resistance arteries by EDHFs, regardless of species and blood vessels tested. We have recently demonstrated that caveolin-1 (Cav-1), which functionally inhibits the activity of endothelial NO synthase (eNOS), is substantially involved in the functional inhibition of eNOS in resistance vessels in mice. However, the significance of the physiological balance between NO and EDHF in cardiovascular homeostasis remains to be elucidated. Methods and Results: We used 3 genotypes of mice including wild-type (WT), Cav-1-knockout (Cav-1-KO) and endothelium-specific eNOS transgenic (eNOS-Tg) mice; in the latter 2 genotypes eNOS activity is genetically up-regulated. Isometric tension experiments showed that in small mesenteric arteries from both Cav-1-KO and eNOS-Tg, NO-mediated relaxations were significantly enhanced, whereas EDHF-mediated responses were markedly reduced (n=7 each). Langendorff experiments also showed that EDHF-mediated coronary flow responses were significantly reduced in both Cav-1-KO and eNOS-Tg (n=6 each). Furthermore, both genotypes showed altered cardiovascular phenotypes, including hypotension in eNOS-Tg and cardiac hypertrophy in Cav-1-KO. Finally, we examined the cardiac responses to chronic pressure overload by transverse aortic constriction (TAC). Both Cav-1-KO and eNOS-Tg showed reduced survival rate after TAC, associated with more progressive left ventricular systolic dysfunction and more reduced coronary flow reserves as compared with WT (n=15 each). Conclusions: These results indicate that the physiological balance between NO and EDHFs plays a crucial role in cardiovascular homeostasis in mice in vivo.
MRP-1 is the dominant MDR protein in ESFT cells and protects cells from chemotherapy-induced cell death.
Authors: Elizabeth Roundhill, Sue Burchill
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3253 

Multi-drug resistance (MDR) is frequently associated with over-expression of the MDR transporter proteins MRP-1and PGP, which function as ATP-dependent pumps to transport anticancer drugs from cells. We have recently shown that MRP-1 is expressed in 92% of primary ESFT (Abstract BACR3, NCRI 2007). The aim of this study was to examine the expression and functional significance of MRP-1 and PGP.    MDR protein expression was examined in six ESFT cell lines by flow cytometry, immunoblot and qRT-PCR. The biological significance of MDR proteins was explored using Calcein-AM flow cytometry in combination with the MRP-1 competitive inhibitor MK571. The effect of inhibitor alone and in combination with vincristine, doxorubicin, actinomycin D or etoposide was investigated. Viable cell number was measured using the trypan blue exclusion assay.    Expression of MRP-1 protein in ESFT cell lines was high compared to the expression of PGP. There was no correlation between MRP-1 mRNA and protein expression detected by either flow cytometry (r=0.166) or immunoblot (r=0.506). MRP-1 protein was detected in both the mitochondria and membrane fractions of ESFT cell lines. Expression of MRP-1 in the mitochondria was inversely proportional to expression in the membrane. Expression of PGP was not identified in the mitochondria.    Inhibition of MRP-1 with MK571 (10-50μM) decreased ESFT viable cell number at 48h; MK571 (50μM) in low (TC-32) and high (SK-N-MC) MRP-1 expressing cells decreased cell viability to 37% and 69% respectively. Pretreatment of ESFT cells for 1h with MK571 (30μM) prior to treatment with vincristine (p=0.003), actinomycin D (p=0.008), fenretinide (p=0.074) and etoposide (p=0.081) resulted in enhanced cell death at 48h. Cells expressing high levels of MRP-1 effluxed more fluorescent calcein than low expressing cell lines (r= 0.93), consistent with the hypothesis that expression of MRP-1 protein correlates with functional activity.    In conclusion, MRP-1 is the dominant MDR protein in ESFT and is expressed in the membrane and mitochondria. The functional significance of mitochondrial MRP-1 is currently under investigation. Knockdown of MRP-1 enhances the responsiveness of ESFT cells to common chemotherapeutic agents and consequently may be of therapeutic benefit to ESFT patients.
Thermogenesis in Brown Adipose Tissue as an Energy Buffer
Authors: Jeffrey S. Flier, Lisa H. Underhill, Jean Himms-Hagen
Journal: New England Journal of Medicine (1984)

DESPITE extensive research on many aspects of obesity, only recently have investigators begun to understand why some persons remain lean for years with no effort to control food intake, whereas others become obese in spite of strenuous efforts to limit intake. In the past few years, studies with laboratory animals have provided an explanation for such large individual variations in energy requirements and have shown that brown adipose tissue buffers changes in food intake.1 2 3 4 When appropriately stimulated, brown adipose tissue dissipates, as heat, energy derived from ingested food. Two types of external stimulus trigger thermogenesis: exposure to cold (that is, . . .
Intestinal Sucrase and Isomaltase Deficiency in Two Siblings
Authors: C M ANDERSON, M MESSER, R R TOWNLEY, M FREEMAN
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 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
The woman who couldn't shoot straight
Authors: Donald W MacCorquodale
Journal: BMJ (2003)

From BMJ USA 2003;Mar:153 

When I was a third-year medical student in the late 1940s, I walked into the Colorado Psychiatric Hospital, where I was going to take a medical history and do a physical examination on a newly admitted patient. While I waited for the elevator, the entry door flew open and two uniformed deputy sheriffs stepped in. They were half-dragging, half-carrying a young woman who was sobbing uncontrollably. Her hair was disheveled, and her face streaked with tears. My heart went out to her. We all stepped into the elevator when it arrived. The deputy sheriffs and their prisoner got off on one floor, and I got off on another.

The next morning, a small group of my …
CT Scanning for Minor Head Injury—Reply
Authors: Marion Smits, Diederik W. J. Dippel, M. G. Myriam Hunink
Journal: JAMA (2006)

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
Abstract P364: Recent Trends In Mortality From Coronary Heart Disease Mortality And Its Risk Factors In Selected Developed Countries
Authors: Akira Sekikawa, Katsuyuki Miura, Bradley Willcox, Kamal H Masaki, Russell P Tracy, Yoshihiro Miyamoto, Hirotsugu Ueshima, Lewis H Kuller
Journal: Circulation (2014)

Objectives: Mortality from coronary heart disease (CHD) in developed countries started to decline in the late 1960’s and early 1970’s and age-adjusted CHD mortality fell about 50%. This decline is attributed to favorable changes in risk factors in the general population, i.e., total cholesterol, blood pressure, smoking, etc., and improved treatment of CHD. We examined recent trends in CHD mortality and its risk factors in selected developed countries. Methods: We selected Australia, Canada, France, Italy, Japan, Spain, Sweden, the UK, and the US. Data on CHD mortality between 1980 and 2005-08 were obtained from the WHO Statistical Information System. To define CHD mortality, codes I20-25 in ICD-10 and corresponding codes in ICDs 8 and 9 were used. Data on risk factors, primarily total cholesterol and systolic blood pressure during the same period were obtained from national surveys as well as literature. Results: in 1980, there was a 2 to 3-fold difference in age-adjusted CHD mortality among these countries both in men and women, with the UK, the US and Canada being high and Japan and France being low. Although between 1980 and 2005-08, age-adjusted CHD mortality continuously declined in all these countries, a 2 to 3-fold difference in the mortality remained with the similar order among these countries. Between 1980 and 2008, age-adjusted mean levels of total cholesterol fell by 21 to 31 mg/dl in men and by 8 to 31 mg/dl in women in these countries except for Japan. Age-adjusted levels of total cholesterol in Japan have continuously increased by 16 mg/dl for both men and women during this period. Meanwhile, between 1980 and 2008 age-adjusted levels of systolic blood pressure fell by 5 to 8 mmHg in men and 6 to 13 mmHg in women in these countries without exception. In 1980, the rate of cigarette smoking in men in Japan was the highest among these countries. Although the rate of smoking in men fell in all these countries, the rates remained the higher in Japan. Conclusions: Age [[Unable to Display Character: &amp;#8211;]]adjusted CHD mortality has continuously declined between 1980 and 2005-08 in these developed countries. The decline was accompanied by a constant decrease in population-levels of total cholesterol by 20 to 30 mg/dl except for Japan where levels of total cholesterol have increased by 16 mg/dl. The reasons for persistently low CHD mortality and its downward trend in Japan are unexplained by traditional risk factors. Identifying preventive factors that determine low CHD rates in the Japanese and implementing such factors to the US would eliminate most of CHD epidemics in the US.
DEATH PRESUMABLY DUE TO THE USE OF THE SALT RESTRICTION TEST IN THE DIAGNOSIS OF ADDISON'S DISEASE
Authors: Curtis F. Garvin, Herbert S. Reichle
Journal: Annals of Internal Medicine (1940)

Case Reports1 August 1940DEATH PRESUMABLY DUE TO THE USE OF THE SALT RESTRICTION TEST IN THE DIAGNOSIS OF ADDISON'S DISEASECURTIS F. GARVIN, M.D., HERBERT S. REICHLE, M.D.CURTIS F. GARVIN, M.D.Search for more papers by this author, HERBERT S. REICHLE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-2-323 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe use of a low salt diet as a diagnostic test in doubtful cases of Addison's disease was suggested by Harrop and his coworkers1 in 1933. Two to five days after beginning the restriction of sodium chloride signs of relapse and characteristic concomitant alterations in the blood occur. That the test is dangerous has been recognized. Cortical extract, as well as intravenous salt solution, must be immediately available in event of a serious crisis.This communication reports a sudden death occurring in a patient with Addison's disease during the period of a salt restriction test. Another report of death, presumably...Bibliography1. HARROPWEINSTEINSOFFERTRESCHER GAALJJH: The diagnosis and treatment of Addison's disease, Jr. Am. Med. Assoc., 1933, c, 1850. CrossrefGoogle Scholar2. LILIENFELD A: The use of the low salt diet in the diagnosis of Addison's disease, Jr. Am. Med. Assoc., 1938, cx, 804. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio*Received for publication March 30, 1939.From the Departments of Medicine and Pathology of Cleveland City Hospital and Western Reserve University School of Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdrenocortical insufficiencyDie Keimdrüsen und ihre KrankheitenAddisonian Crisis Precipitated by NephrectomySudden “exhaustive” death in excited patientsA case of Addison's disease associated with primary amenorrhea 1 August 1940Volume 14, Issue 2Page: 323-324KeywordsBloodDietHospital medicineSaltsSodium chloride Issue Published: 1 August 1940 PDF downloadLoading ...
THE DISADVANTAGES OF SULFONAMIDE COMBINATIONS
Authors: W CARROL
Journal: Annals of Internal Medicine (1948)

Case Reports1 September 1948THE DISADVANTAGES OF SULFONAMIDE COMBINATIONSWILFRED CARROL, M.D.WILFRED CARROL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-29-3-533 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRecently there have appeared reports in the literature advocating the use of "sulfonamide combinations."1, 2The purpose in giving combinations of these similarly acting drugs has been to reduce the danger of "intrarenal drug precipitation" and "concrement formation." While giving comparatively small doses of each component of a mixture of sulfonamides, the danger of intrarenal drug precipitation should be only as great as if each compound had been administered alone. Yet the sum of the components could be completely effective in eradication of a given infection. This method of sulfonamide therapy at first sight appears very desirable but a case...Bibliography1. LEHR D: Inhibition of drug precipitation in the urinary tract by the use of sulfonamide mixtures. I. Sulfathiazole-sulfadiazine mixture, Proc. Soc. Exper. Biol. and Med., 1945, lviii, 11. CrossrefGoogle Scholar2. FRISKHAGENMANHELANDERSJÖGREN ARGSB: "Sulfa-Combination," New chemotherapeutic principle, British Med. Jr., 1947, l, 7. CrossrefGoogle Scholar3. BLANKENHORNVILTER MACF: Toxic reactions of the newer sulfonamides, Jr. Am. Med. Assoc., 1944, cxxvi, 691. Google Scholar4. FINLANDPETERSONGOODWIN MOLRA: Sulfadiazine, further clinical studies of its efficacy and toxic effects, Ann. Int. Med., 1942, xvii, 920. Google Scholar5. DOWLINGLEPPER HFMH: Toxic reactions following therapy with sulfapyridine, sulfathiazole and sulfadiazine, Jr. Am. Med. Assoc., 1943, cxxi, 1190. CrossrefGoogle Scholar6. DOWLING HF: Relative toxicity of sulfamerazine and sulfadiazine, Jr. Am. Med. Assoc., 1944, cxxv, 103. CrossrefGoogle Scholar7. SCHWARTZFLIPPINREINHOLDDOMM LHFJGAH: The effects of alkali on crystalluria from sulfathiazole and sulfadiazine, Jr. Am. Med. Assoc., 1941, cxvii, 514. CrossrefGoogle Scholar8. GILLIGANGARBPLUMMER DRSN: Prevention of crystalluria during sulfadiazine therapy, Proc. Soc. Exper. Biol. and Med., 1943, lii, 248. CrossrefGoogle Scholar9. GILLIGANGARBWHEELERPLUMMER DRSCN: Adjuvant alkali therapy in prevention of renal complications from sulfadiazine, Jr. Am. Med. Assoc., 1943, cxxii, 1160. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Newark, N. J.*Received for publication July 31, 1947. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAntibacterial Chemotherapy with Sulfonamides 1 September 1948Volume 29, Issue 3Page: 533-536KeywordsDrugsSulfonamide ePublished: 1 December 2008 Issue Published: 1 September 1948 PDF downloadLoading ...
A sporadic case of progressive mucinous histiocytosis
Authors: U. Sass, J. André, M. Song
Journal: British Journal of Dermatology (2000)

Hereditary progressive mucinous histiocytosis is a rare autosomal dominant non‐Langerhans cell histiocytosis. We describe a sporadic case of this syndrome in a 64‐year‐old woman who had multiple dark‐red dome‐shaped papulonodules located mainly on the back of her hands, forearms and thighs. Light microscopy revealed a circumscribed upper dermal aggregate of ovoid or spindle‐shaped histiocytes with abundant mucin deposition. Iron deposits and numerous mast cells were scattered throughout the tumour but giant cells were rare. Electron microscopy revealed a high number of zebra bodies and myeloid bodies in the cytoplasm of the histiocytes. Immunohistochemistry showed positive labelling with alpha‐1 antitrypsin, Factor XIIIa and CD68, while CD1a, CD34 and S100 protein were negative. The differential diagnosis of histiocytic syndromes is discussed.
Abstract 1671: Immunosuppressive myeloid-derived suppressor cells expressing PDL1 are increased in human melanoma tumor tissue
Authors: Kimberly Rae Jordan, Virginia Borges, Martin D. McCarter
Journal: Cancer Research (2014)

Abstract Despite the ability to elicit active immune responses, most immunotherapies fail to eliminate tumors in human cancer patients. One reason immunotherapy has not met expectations may be due to immunosuppression in the local environment of the tumor. Immunosuppressive myeloid-derived suppressor cells (MDSCs) are increased in the peripheral blood of melanoma patients and the frequency of MDSCs correlates with overall survival and disease progression. Furthermore, cytokines related to the recruitment and differentiation of MDSCs are also increased in melanoma patient serum and changes in these cytokine levels may correlate with disease progression. We find an increased frequency of regulatory T cells, PD-1-expressing T cells, and PD-L1 expressing MDSCs in primary melanoma tumors, suggesting that PD-1/PD-L1 interactions may play a role in immunosuppression in the microenvironment of the tumor. We are currently investigating the mechanisms of immunosuppression used by human MDSCs and whether the suppressive function of MDSCs can be blocked with antibodies targeting PD-L1. In conclusion, we have established MDSCs as an important player in immunosuppression in melanoma patients suggesting that combinatorial treatments that reduce the frequency or activity of MDSCs may improve the effectiveness of future immunotherapies. Citation Format: Kimberly Rae Jordan, Virginia Borges, Martin D. McCarter. Immunosuppressive myeloid-derived suppressor cells expressing PDL1 are increased in human melanoma tumor tissue. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1671. doi:10.1158/1538-7445.AM2014-1671
Abstract P074: Caffeine Intake May be Associated with a Lower Risk of Type 2 Diabetes in the Physicians’ Health Study and Meta-Analysis
Authors: Chisa Matsumoto, Howard D Sesso, Howard D Sesso, J. Michael Gaziano, Luc Djoussé
Journal: Circulation (2014)

Objectives: Short-term metabolic studies have shown that caffeine improves insulin-sensitivity. However, epidemiological studies evaluating the relationship of caffeine intake with risk of type 2 diabetes (DM) have shown inconsistent results. We examined whether caffeine intake is associated with the risk of DM in the Physicians’ Health Study and supplemented the results with a meta-analysis. Methods: We prospectively analyzed data on 18,432 PHS participants that were free of DM at baseline (1997-2001). Caffeine intake was assessed using a food-frequency questionnaire. Incident DM was ascertained via annual follow-up questionnaires and validated in a subsample by review of medical records. We used Cox proportional hazards models to estimate the HR and 95% CI of DM. Meta-analysis was conducted through a systematic literature search using PubMed and EMBASE. A random-effect model was used and between-studies heterogeneity was estimated with I 2 . Results: In the PHS, mean age at baseline was 66.4 ± 9.3 years, and 1,137 men (6.2%) developed DM during mean follow up of 9.2 years. In a multivariable model adjusted for conventional risk factors of DM, HRs (95% CI) for DM were 1.0 (ref), 1.08 (0.90-1.29), 1.03 (0.85-1.24), 0.98 (0.81-1.18), and 0.86 (0.70-1.04) across consecutive quintiles of caffeine intake (p for linear trend= 0.69). Meta-analysis included 6 studies consisted of 7 separate cohorts comprising 275,971 individuals and 10,048 cases of incident DM. The pooled odds ratio (95% CI) for DM was 0.79 (0.68-0.93) when the highest caffeine intake was compared to the lowest group in random effects model (I 2 =75%). Conclusion: While only the highest category of caffeine intake was associated with a modest and non-significant association with DM in the PHS, results from the meta-analysis were consistent with a lower risk of DM.