tbuckley/cabot-search huggingface dataset:
Nitric oxide accounts for dose-dependent estrogen-mediated coronary relaxation after acute estrogen withdrawal.
Authors: P Collins, J Shay, C Jiang, J Moss
Journal: Circulation (1994)

BACKGROUND Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women, and estrogen treatment modulates endothelium-dependent vasodilation in ovariectomized, atherosclerotic monkeys. Estradiol-17 beta also induces relaxation in isolated rabbit coronary arteries as well as cerebral basilar arteries. The estrogen concentrations required to induce such relaxation are in the pharmacological range (10(-6) to 10(-5) mol/L). METHODS AND RESULTS The present study was designed to test whether the sensitivity and specificity of the relaxing response of coronary vascular smooth muscle to exogenous estradiol-17 beta is dependent on the sex hormone status of the animal. In coronary artery rings contracted with PGF2 alpha (3 x 10(-5) mol/L), estradiol-17 beta caused significant relaxation at a physiological estrogen concentration (10(-9) mol/L), in coronary artery rings from oophorectomized, estrogen-treated and acutely estrogen-withdrawn rabbits only. Relaxation induced by estradiol-17 beta at lower concentrations (10(-9) to 10(-6) mol/L) in these rings was 20 +/- 6%, 42 +/- 8%, 54 +/- 9%, and 75 +/- 8%, respectively, compared with 4 +/- 2%, 12 +/- 5%, 16 +/- 7%, and 25 +/- 12% and 5 +/- 2%, 12 +/- 5%, 18 +/- 8%, and 23 +/- 10% in rings from estrogen-maintained and oophorectomized rabbits, respectively (P &lt; .01). The relaxation in coronary artery rings from estrogen-treated and acutely estrogen-withdrawn rabbits was endothelium and nitric oxide dependent since it was abolished by endothelium removal and the nitric oxide synthase inhibitor N omega-nitro-L-arginine. CONCLUSIONS This study demonstrates that estrogen-induced, endothelium-dependent relaxation of coronary arteries may, in some species, depend on the sex hormone status of the animal. These findings may help to better understand the effects of ovarian steroids in the coronary circulation of females.
Persistent defective coupling of dopamine-1 receptors to G proteins after solubilization from kidney proximal tubules of hypertensive rats.
Authors: A Sidhu, P Vachvanichsanong, P A Jose, R A Felder
Journal: Journal of Clinical Investigation (1992)

The natriuretic effect of dopamine-1 (DA-1) agonists is reduced in spontaneously hypertensive rat (SHR), partly because of defective DA-1 receptor-adenylate cyclase (AC) coupling in renal proximal convoluted tubules. To investigate this defective coupling, DA-1 dopamine receptors from renal proximal tubules were solubilized and reconstituted into phospholipid vesicles. The binding of DA-1-selective ligand [125I]SCH 23982 was specific and saturable, with no differences in receptor density or Kd between SHR and normotensive rats (Wistar-Kyoto rats; WKY). Competition experiments of the reconstituted DA-1 dopamine receptors in WKY with a DA-1-selective agonist, SKF R-38393, revealed the presence of high- (Kh = 350 +/- 209 nM) and low-affinity (Kl = 70,500 +/- 39,500 nM) binding sites. 100 microM Gpp(NH)p abolished the agonist high-affinity sites, converting them to a low-affinity state (Ki = 33,650 +/- 10,850 nM). In SHR, one affinity site was noted (Ki = 13,800 +/- 500) and was not modulated by Gpp(NH)p (Ki = 11,505 +/- 2,295). The absence of guanine nucleotide-sensitive agonist high-affinity sites may explain the defective DA-1/AC coupling mechanism in the SHR.
Preserving Renal Function in Patients with Membranous Nephropathy: Daily Oral Chlorambucil Compared with Intermittent Monthly Pulses of Cyclophosphamide
Authors: Louis J. M. Reichert
Journal: Annals of Internal Medicine (1994)

Objective: To compare oral chlorambucil and intravenous cyclophosphamide-based drug regimens in the treatment of patients with membranous nephropathy and deteriorating renal function. Design: Randomized study. Setting: University hospital and teaching hospitals. Patients: 18 patients with membranous nephropathy, a nephrotic syndrome, and deteriorating renal function. Intervention: Chlorambucil (0.15 mg/kg body weight per day orally in months 2, 4, and 6) and prednisone (three intravenous pulses of 1 g of methylprednisolone followed by oral prednisone at 0.5 mg/kg per day in months 1, 3, and 5) or intravenous cyclophosphamide (750 mg/m2 body surface area once every month for 6 months) and methylprednisolone (three intravenous 1-g pulses in months 1, 3, and 5). Measurements: Serum creatinine, serum cholesterol, serum albumin, and urinary protein levels. Results: Before treatment, no statistical differences were found between the treatment groups. Six months after treatment was started, serum creatinine levels had decreased in the group treated with chlorambucil, methylprednisolone, and prednisone from a mean of 260 ± 112 µmol/L to 186 ± 74 µmol/L (P = 0.003) and had increased in the group treated with intravenous cyclophosphamide and methylprednisolone from 218 ± 85 µmol/L to 297 ± 143 µmol/L (P = 0.02; difference between both groups, P < 0.001). Serum albumin levels increased in both groups by 9 and 6 g/L, respectively, and the urinary protein/creatinine ratio decreased by 2.6 and 3.1 g/10 mmol, respectively. At the end of follow-up (median, 15 months; range, 6 to 36 months), one patient in the chlorambucil group and four patients in the cyclophosphamide group had reached end-stage renal failure after 36, 12, 12, 18, and 18 months of therapy, respectively. One patient in the intravenous cyclophosphamide group died after 6 months of therapy. Conclusions: Thus far, both oral chlorambucil and oral cyclophosphamide have been shown to be effective in the treatment of patients with membranous nephropathy and deteriorating renal function. Our study shows that intermittent monthly pulses of low-dose cyclophosphamide are ineffective in preserving renal function in such patients.
Population-level impact of vouchers on access to health facility delivery for women in Kenya: a quasi-experimental study
Authors: Francis Obare, Charlotte Warren, Timothy Abuya, Ian Askew, Ben Bellows
Journal: The Lancet (2013)

BackgroundAvailable evidence indicates that vouchers improve service utilisation among the target populations. A key question is whether increased utilisation results from improved access or from shifting clients from non-accredited to contracted service providers. This paper examines whether the safe motherhood voucher programme in Kenya is associated with improved access to health facility delivery over time using information on births within 2 years preceding baseline and follow-up surveys in voucher and comparison sites.MethodsData were collected in 2010–11, and in 2012, among 2933 and 3094 women aged 15–49 years reporting 962 and 1494 births within 2 years before the respective surveys. Respondents were sampled from among those living within a 5 km radius of three groups of facilities: those nearby health facilities that had been in the voucher programme since 2006; those nearby facilities that were added to the programme in 2010–11; and those nearby similar facilities in comparison sites. Analysis entails cross-tabulations and estimation of multilevel random-intercept logit models.FindingsThe proportion of births occurring at home declined by more than 10 percentage points, while the proportion of births delivered in health facilities increased by a similar margin over time in voucher sites. The increase in facility-based births was consistent across public and private health facilities. There was also a significant increase in the likelihood of facility-based delivery (odds ratio 2·04; 95% CI 1·40–2·98 in the 2006 voucher arm; 1·72; 1·22–2·43 in the 2010–11 voucher arm), which was accompanied by significant decline in home-based births in voucher sites over time. By contrast, there were no significant changes in the likelihood of facility or home-based delivery in the comparison sites over time.InterpretationThe voucher programme contributed to improved access to institutional delivery by shifting births from home to health facilities over time.FundingThe reproductive health vouchers programme is implemented by the Government of Kenya with major funding from the German Development Bank. The evaluation project was funded by the Bill & Melinda Gates Foundation.
Issues Regarding Antiretroviral Treatment for Patients With HIV-1 Infection
Authors: Conrad Fischer
Journal: JAMA (1997)

To the Editor.  —In their 1991 report, HIV Disease in Correc-  tional Facilities , the Presidential National Commission on AIDS recommends that  and treatment available to HIV-infected inmates in correctional facilities should be equal to that available to HIV-infected individuals in the general community.  Dr Carpenter and colleagues 2 and Dr Quinn 3 recommend treatment of acute primary HIV infections with combination antiretroviral regimens that include 2 nucleoside reverse transcriptase inhibitors and a protease inhibitor.  Incarcerated populations have higher prevalence rates of HIV infection than the general nonincarcerated population. As unprotected sexual intercourse and sharing of syringes and needles for injection continue to occur within correctional facilities, new cases of HIV infection among inmates most certainly will take place. A considerable number of these newly infected inmates will present with symptomatic primary HIV infections, also referred to as the acute retroviral syndrome. Therefore we believe that primary care clinicians in correctional facilities have
BMA rules out move to "super hospitals"
Authors: L. Beecham
Journal: BMJ (1997)

The leader of Britain's hospital consultants has warned that moves to build “super hospitals” serving large populations would be disastrous and would not save money and that any radical reorganisation of the hospital service would need careful strategic planning.



Mr James Johnson said that bigger is not always better

CHARLES MILLIGAN



The drive towards greater specialisation seems to favour larger hospitals and it has been suggested this would save money and achieve better clinical results. Speaking at last week's …
CAN THE POOR BOY SECURE A MEDICAL EDUCATION?
Authors: N. P. COLWELL
Journal: JAMA (1923)

In order to obtain the facts regarding the opportunities for students of limited means to obtain a medical education, correspondence has been conducted with the presidents of fifty prominent universities. The inquiry included the possibilities of obtaining the essential premedical college work as well as the work in the medical school. <h3>PREMEDICAL COLLEGE WORK</h3> The replies in regard to securing the premedical college training showed that the opportunities were even more numerous than was anticipated. From the universities which had kept fair records in regard to students' self help, we learn that from 50 to 65 per cent. of the student body are working for at least a part of their expenses, and that between 15 and 20 per cent. are making their entire way through college. Some of these were granted scholarships which covered all or part of their tuition fees, but in no instance covered other essential expenses.
Images plus text work best to put people off smoking
Authors: A. Tuffs
Journal: BMJ (2009)

Health warnings on cigarette packs that combine strong pictures with written warnings are most effective in motivating smokers to quit smoking and deterring those who have never smoked or who have quit. The warnings should cover at least half of the packet and be part of a mass media campaign.

This is the conclusion of a report from the German World Health Organization tobacco control centre in Heidelberg, which presents the results of 20 international studies …
Medication Compliance in Non-insulin-dependent Diabetes: A Randomized Comparison of Chlorpropamide and Insulin
Authors: Andrew K Diehl, Nancy J Sugarek, Richard L Bauer
Journal: Diabetes Care (1985)

Medication compliance may be a problem in the management of patients with diabetes. Some physicians initially treat patients having non-insulin-dependent diabetes with oral sulfonylureas because they fear greater compliance problems with insulin therapy. We compared compliance with insulin and chlorpropamide in patients newly beginning medication for NIDDM. Seventy-seven adults with hyperglycemia despite diet therapy were randomly assigned to chlorpropamide or insulin. Compliance was measured four times over 24 wk. Patients then crossed over to the other medication and were followed for 24 additional weeks. Overall, there were no differences in compliance with the two medications in terms of percent of prescription used, proportion taking at least 80% of prescribed medication, self-report of medication or diet compliance, or protocol dropout rates. However, treatment satisfaction was higher with chlorpropamide, and most patients preferred chlorpropamide to insulin (P &amp;lt; 0.0001). While such differences in satisfaction may affect long-term compliance, physicians should not assume that their patients will be less compliant with insulin than with oral sulfonylureas.
Gastric Aspiration in Localization of Gastrointestinal Hemorrhage
Authors: Gordon D. Luk
Journal: JAMA (1979)

We compared the findings from gastric aspiration for blood with the site of gastrointestinal (GI) hemorrhage ultimately identified by endoscopy or angiography in 1,190 patients whose cases were analyzed retrospectively and prospectively during a six-year period. Gastric aspirates were positive for blood in 837 patients. An upper GI site proximal to Treitz' ligament was identified in 93%, and none had a lower GI site. A negative aspirate was found in 353 patients; a lower GI site was identified in 60%, and 1% (three patients) had an upper GI site. In these three patients, hemorrhage occurred in clinical settings suggesting ulcer disease, and bleeding duodenal ulcers were found in all three. All of the other 180 patients with a bleeding duodenal ulcer had a positive gastric aspirate.
Biosynthesis and secretion of human colonic mucin glycoproteins.
Authors: A C Smith, D K Podolsky
Journal: Journal of Clinical Investigation (1987)

Synthesis and secretion of colonic mucin glycoprotein species were assessed during in vitro culture of colonic mucosal explants. DEAE-cellulose chromatography of endogenously labeled mucin glycoproteins from explant tissue demonstrated the presence of six mucin species (I-VI) similar to those identified earlier in surgical specimens of human colonic tissue. The relative proportions of mucin species I-VI in tissue explants remained constant throughout a 30-h culture period. However, the proportional representation of the various mucin species in media was significantly different from that found in tissue, which suggests that some mucin species (I, II, and III) are differentially secreted, whereas others (IV and V) are retained within intracellular pools. Radiolabeled precursors were incorporated into mucin species I, II, and III at a 2.0-2.6-fold greater rate than their concentration in tissue, supporting the concept that these glycoproteins were both synthesized and secreted at a greater rate than species IV and V. Colonic mucosal explants from patients with ulcerative colitis showed greater than 90% reduction of species IV. However, the amount of species IV recovered from culture media of ulcerative colitis explants was comparable to normal controls. It appears that mucin species IV is differentially secreted rather than retained within intracellular pools in mucosa of patients with ulcerative colitis.
Mice deficient for the IL-3/GM-CSF/IL-5 βc receptor exhibit lung pathology and impaired immune response, while βIL3 receptor-deficient mice are normal
Authors: Ryuichi Nishinakamura, Naoki Nakayama, Yoko Hirabayashi, Tohru Inoue, Dee Aud, Tom Mcneil, Sadahiro Azuma, Shosei Yoshida, Yutaka Toyoda, Ken-ichi Aral, Atsushi Miyajima, Richard Murray
Journal: Immunity (1995)
Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression.
Authors: T Taga, Y Kawanishi, R R Hardy, T Hirano, T Kishimoto
Journal: The Journal of Experimental Medicine (1987)

B cell stimulatory factor 2 receptors (BSF-2-R) were studied using radioiodinated recombinant BSF-2 with a specific activity of 6.16 X 10(13) cpm/g. Kinetic studies showed that binding of 125I-BSF-2 to CESS cells reached maximum level within 150 min at 0 degrees C. There was a single class of receptors with high affinity (Kd 3.4 X 10(-10) M) on CESS, and the number of receptors was 2,700 per cell. Binding of 125I-BSF-2 to CESS was competitively inhibited by unlabeled BSF-2 but not by IL-1, IL-2, IFN-beta, IFN-gamma, and G-CSF, indicating the presence of the receptors specific for BSF-2. EBV-transformed B lymphoblastoid cell lines (CESS, SKW6-CL4, LCL13, and LCL14) expressed BSF-2-R, whereas Burkitt's lines did not. EBV or EBNA2 did not induce the expression of the receptors on Burkitt's cells. The plasma cell lines (ARH-77 and U266) expressed BSF-2-R, fitting the function of BSF-2 as plasma cell growth factor. Several other cell lines, the histiocytic line U937, the promyelocytic line HL60, the astrocytoma line U373 and the glioblastoma line SK-MG-4, in which BSF-2 was inducible with IL-1 or TPA, displayed BSF-2-R with Kd in the range of 1.3-6.4 X 10(-10) M, suggesting the autocrine mechanism in BSF-2 function. The four T cell lines (CEM, HSB, Jurkat, and OM 1) did not express a detectable number of receptors, but normal resting T cells expressed 100-1,000 receptors per cell. BSF-2-R were not present on normal resting B cells but expressed on activated B cells with a Kd of 3.6-5.0 X 10(-10) M, fitting the function of BSF-2, which acts on B cells at the final maturation stage to induce immunoglobulin production.
THE CASE AGAINST THE A. B. &amp;amp; S. PILL
Authors: Fredrick F. Yonkman
Journal: JAMA (1934)

The cathartic agent known as the A. B. & S. pill, even though relegated to the National Formulary, is still rather freely recommended by some practitioners and consequently is promiscuously used by the public. Hence there are frequent disastrous consequences when these pills are eaten by unsuspecting youngsters who presume that the beautifully colored and sugar-coated pellets are candy rather than deadly buckshot by virture of the contained strychnine which accompanies the belladonna and aloin.  The danger of all disguised medicants containing strychnine is vividly portrayed by Aikman 1 in his analysis of agents responsible for death preceded by convulsions in children under 5 years of age. He finds that strychnine in the form of Hinckle's, A. B. & S., and A. B. S. & C. pills or tablets is the most frequent causative poisoning agent.  In 1929 in Dr. O. H. Plant's laboratory at Iowa City, experiments 2 with
The Colloidal Gold Test Of the Spinal Fluid
Authors: Joseph B. Green
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Nicholas J. Fiumara, MD (Question and Answers,<b>208</b>:2168, 1969), stated in reply to a question about Lange's colloidal gold test, that it "offers little more in diagnostic help than the total protein test [of cerebrospinal fluid]." This statement may be valid in respect to the diagnosis of neurosyphilis but is incorrect if applied to neurologic diagnosis in general.<sup>1</sup>Multiple sclerosis and subacute sclerosing panencephalitis are two diseases often associated with an abnormal gold curve in the presence of a normal cerebrospinal fluid total protein value. In fact, an abnormal gold curve may call attention to these diagnostic possibilities, when they have not been previously suspected. In such cases a sample of cerebrospinal fluid should be sent to a more specialized laboratory which can perform electrophoretic studies.
Abstract 1241: Kaempferol suppresses solar ultraviolet radiation-induced skin cancers by targeting RSK2 and MSK1
Authors: Ke Yao, Hanyong Chen, Mee-Hyun Lee, Alyssa Langfald, Myoung Ok Kim, Dong Hoon Yu, Kangdong Liu, Wei-Ya Ma, Ann M. Bode, Ziming Dong, Zigang Dong
Journal: Cancer Research (2014)

Abstract Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, which is the most common form of cancer in the United States. Discovering novel chemopreventive agents against this disease is extremely important. Kaempferol, a natural flavonol isolated from tea, broccoli, grapes, apples and other plant sources, is known to have anticancer activity, but its molecular mechanisms and direct target(s) in cancer chemoprevention are still unclear. In this study, our pull-down assay results showed that RSK2 and MSK1 directly interact with kaempferol in both ex vivo and in vitro systems. ATP competition and in vitro kinase assay data revealed that kaempferol interacts with RSK2 and MSK1 at the ATP-binding pocket and inhibits their respective kinase activities. Mechanistic investigations determined that kaempferol acts as an inhibitor of RSK2 and MSK1 kinase activities to attenuate solar UV-induced phosphorylation in mitogen-activated protein kinase signaling cascades in JB6 P+ mouse skin epidermal cells. In a mouse skin tumorigenesis study, kaempferol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis showed that the kaempferol-treated group had a substantial reduction in solar UV-induced phosphorylation of CREB and c-Fos in mouse skin. Taken together, our results identify kaempferol as a safe and novel chemopreventive agent against solar UV-induced skin carcinogenesis that acts by targeting RSK2 and MSK1. Citation Format: Ke Yao, Hanyong Chen, Mee-Hyun Lee, Alyssa Langfald, Myoung Ok Kim, Dong Hoon Yu, Kangdong Liu, Wei-Ya Ma, Ann M. Bode, Ziming Dong, Zigang Dong. Kaempferol suppresses solar ultraviolet radiation-induced skin cancers by targeting RSK2 and MSK1. [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 1241. doi:10.1158/1538-7445.AM2014-1241