tbuckley/cabot-search huggingface dataset:
Government tries to end confusion over swine flu advice to pregnant women
Authors: A. O'Dowd
Journal: BMJ (2009)

The government has issued new guidance to try to end the confusion over advice to pregnant women on how to avoid the A/H1N1 virus.

The guidance comes after a weekend of conflicting messages from different sources, such as the Department of Health, the National Childbirth Trust, and medical royal colleges.

The National Childbirth Trust issued advice suggesting that women should consider delaying conception. The trust said that the guidance was taken from the health department’s website.

A joint statement from the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives said that current advice was for pregnant women to avoid crowded places whenever possible in times of flu outbreaks.

The health department subsequently posted a new document on its website reiterating previously issued advice but emphasised that it was no longer telling women to delay conception or to stay away from busy workplaces or transport.

A statement from England’s chief medical officer, Liam Donaldson, said that the health department was not advising pregnant women to avoid going to work …
Effects of Protoveratrine, Serotonin and ATP on Afferent and Splanchnic Nerve Activity
Authors: A. S. DONTAS
Journal: Circulation Research (1955)

Splanchnic outflow was studied along with carotid and aortic presso- and chemoreceptor inflow in cats under a variety of conditions. Splanchnic activity was increased by a decrease in presso- or increase in chemoreceptor activity and vice-versa. Blood pressure rose following splanchnic activation. Protoveratrine and serotonin, reported to activate the "coronary chemoreflex," depressed completely splanchnic outflow, without enhancing pressoreceptor activity. Prolonged hypotension from protoveratrine coincided with partial return of splanchnic activity and tonic discharge of pressoreceptors. ATP increased splanchnic activity simultaneously with the hypotension and it is suggested that it be excluded from the list of drugs eliciting the "coronary chemoreflex."
Impact of radiation and hepatitis virus infection on risk of hepatocellular carcinoma
Authors: Waka Ohishi, Saeko Fujiwara, John B. Cologne, Gen Suzuki, Masazumi Akahoshi, Nobuo Nishi, Masataka Tsuge, Kazuaki Chayama
Journal: Hepatology (2011)

In cohort studies of atomic bomb survivors and Mayak nuclear facility workers, radiation-associated increases in liver cancer risk were observed, but hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were not taken strictly into account. We identified 359 hepatocellular carcinoma (HCC) cases between 1970 and 2002 in the cohort of atomic bomb survivors and estimated cumulative incidence of HCC by radiation dose. To investigate contributions of radiation exposure and hepatitis virus infection to HCC risk, we conducted a nested case-control study using sera stored before HCC diagnosis in the longitudinal cohort of atomic bomb survivors. The study included 224 HCC cases and 644 controls that were matched to the cases on gender, age, city, and time and method of serum storage, and countermatched on radiation dose. The cumulative incidence of HCC by follow-up time and age increased significantly with radiation dose. The relative risk (RR) of HCC for radiation at 1 Gy was 1.67 (95% confidence interval: 1.22-2.35) with adjustment for alcohol consumption, body mass index (BMI), and smoking habit, whereas the RRs for HBV or HCV infection alone were 63 (20-241) and 83 (36-231) with such adjustment, respectively. Those estimates changed little when radiation and hepatitis virus infection were fit simultaneously. The RR of non-B, non-C HCC at 1 Gy was 1.90 (1.02-3.92) without adjustment for alcohol consumption, BMI, or smoking habit and 2.74 (1.26-7.04) with such adjustment. Conclusion: These results indicate that radiation exposure and HBV and HCV infection are associated independently with increased HCC risk. In particular, radiation exposure was a significant risk factor for non-B, non-C HCC with no apparent confounding by alcohol consumption, BMI, or smoking habit. (HEPATOLOGY 2011;53:-)
Role of counterregulatory hormones in the catabolic response to stress.
Authors: R A Gelfand, D E Matthews, D M Bier, R S Sherwin
Journal: Journal of Clinical Investigation (1984)

Patients with major injury or illness develop protein wasting, hypermetabolism, and hyperglycemia with increased glucose flux. To assess the role of elevated counterregulatory hormones in this response, we simultaneously infused cortisol (6 mg/m2 per h), glucagon (4 ng/kg per min), epinephrine (0.6 microgram/m2 per min), and norepinephrine (0.8 micrograms/m2 per min) for 72 h into five obese subjects receiving only intravenous glucose (150 g/d). Four obese subjects received cortisol alone under identical conditions. Combined infusion maintained plasma hormone elevations typical of severe stress for 3 d. This caused a sustained increase in plasma glucose (60-80%), glucose production (100%), and total glucose flux (40%), despite persistent hyperinsulinemia. In contrast, resting metabolic rate changed little (9% rise, P = NS). Urinary nitrogen excretion promptly doubled and remained increased by approximately 4 g/d, reflecting increased excretion of urea and ammonia. Virtually all plasma amino acids declined. The increment in nitrogen excretion was similar in three additional combined infusion studies performed in 3-d fasted subjects not receiving glucose. Cortisol alone produced a smaller glycemic response (20-25%), an initially smaller insulin response, and a delayed rise in nitrogen excretion. By day 3, however, daily nitrogen excretion was equal to the combined group as was the elevation in plasma insulin. Most plasma amino acids rose rather than fell. In both infusion protocols nitrogen wasting was accompanied by only modest increments in 3-methylhistidine excretion (approximately 20-30%) and no significant change in leucine flux. We conclude: (a) Prolonged elevations of multiple stress hormones cause persistent hyperglycemia, increased glucose turnover, and increased nitrogen loss; (b) The sustained nitrogen loss is no greater than that produced by cortisol alone; (c) Glucagon, epinephrine, and norepinephrine transiently augment cortisol-induced nitrogen loss and persistently accentuate hyperglycemia; (d) Counterregulatory hormones contribute to, but are probably not the sole mediators of the massive nitrogen loss, muscle proteolysis, and hypermetabolism seen in some clinical settings of severe stress.
Marijuana and Cocaine Impair Alveolar Macrophage Function and Cytokine Production
Authors: GAYLE COCITA BALDWIN, DONALD P. TASHKIN, DAWN M. BUCKLEY, ALICE N. PARK, STEVEN M. DUBINETT, MICHAEL D. ROTH
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Use of marijuana and cocaine is on the rise in the United States. Although pulmonary toxicity from these drugs has occasionally been reported, little is known about their effects on the lung microenvironment. We evaluated the function of alveolar macrophages (AMs) recovered from the lungs of nonsmokers and habitual smokers of either tobacco, marijuana, or crack cocaine. AMs recovered from marijuana smokers were deficient in their ability to phagocytose Staphylococcus aureus (p < 0.01). AMs from marijuana smokers and from cocaine users were also severely limited in their ability to kill both bacteria and tumor cells (p < 0.01). Studies using N G-monomethyl-l-arginine monoacetate, an inhibitor of nitric oxide synthase, suggest that AMs from nonsmokers and tobacco smokers were able to use nitric oxide as an antibacterial effector molecule, while AMs from smokers of marijuana and cocaine were not. Finally, AMs from marijuana smokers, but not from smokers of tobacco or cocaine, produced less than normal amounts of tumor necrosis factor- α , granulocyte-macrophage colony-stimulating factor, and interleukin-6 when stimulated in culture with lipopolysaccharide. In contrast, the production of transforming growth factor- β , an immunosuppressive cytokine, was similar in all groups. These findings indicate that habitual exposure of the lung to either marijuana or cocaine impairs the function and/or cytokine production of AMs. The ultimate outcome of these effects may be an enhanced susceptibility to infectious disease, cancer, and AIDS.
Prion subcellular fractionation reveals infectivity spectrum, with a high titre-low PrPreslevel disparity
Authors: Victoria Lewis, Cathryn L Haigh, Colin L Masters, Andrew F Hill, Victoria A Lawson, Steven J Collins
Journal: Molecular Neurodegeneration (2012)

Abstract Background Prion disease transmission and pathogenesis are linked to misfolded, typically protease resistant (PrP res ) conformers of the normal cellular prion protein (PrP C ), with the former posited to be the principal constituent of the infectious 'prion'. Unexplained discrepancies observed between detectable PrP res and infectivity levels exemplify the complexity in deciphering the exact biophysical nature of prions and those host cell factors, if any, which contribute to transmission efficiency. In order to improve our understanding of these important issues, this study utilized a bioassay validated cell culture model of prion infection to investigate discordance between PrP res levels and infectivity titres at a subcellular resolution. Findings Subcellular fractions enriched in lipid rafts or endoplasmic reticulum/mitochondrial marker proteins were equally highly efficient at prion transmission, despite lipid raft fractions containing up to eight times the levels of detectable PrP res . Brain homogenate infectivity was not differentially enhanced by subcellular fraction-specific co-factors, and proteinase K pre-treatment of selected fractions modestly, but equally reduced infectivity. Only lipid raft associated infectivity was enhanced by sonication. Conclusions This study authenticates a subcellular disparity in PrP res and infectivity levels, and eliminates simultaneous divergence of prion strains as the explanation for this phenomenon. On balance, the results align best with the concept that transmission efficiency is influenced more by intrinsic characteristics of the infectious prion, rather than cellular microenvironment conditions or absolute PrP res levels.
Aberrant Glycosylation and Localization of Polycystin-1 Cause Polycystic Kidney in an AQP11 Knockout Model
Authors: Yuichi Inoue, Eisei Sohara, Katsuki Kobayashi, Motoko Chiga, Tatemitsu Rai, Kenichi Ishibashi, Shigeo Horie, Xuefeng Su, Jing Zhou, Sei Sasaki, Shinichi Uchida
Journal: Journal of the American Society of Nephrology (2014)

We previously reported that disruption of the aquaporin-11 (AQP11) gene in mice resulted in cystogenesis in the kidney. In this study, we aimed to clarify the mechanism of cystogenesis in AQP11(−/−) mice. To enable the analyses of AQP11 at the protein level in vivo, AQP11 BAC transgenic mice (TgAQP11) that express 3×HA-tagged AQP11 protein were generated. This AQP11 localized to the endoplasmic reticulum (ER) of proximal tubule cells in TgAQP11 mice and rescued renal cystogenesis in AQP11(−/−) mice. Therefore, we hypothesized that the absence of AQP11 in the ER could result in impaired quality control and aberrant trafficking of polycystin-1 (PC-1) and polycystin-2 (PC-2). Compared with kidneys of wild-type mice, AQP11(−/−) kidneys exhibited increased protein expression levels of PC-1 and decreased protein expression levels of PC-2. Moreover, PC-1 isolated from AQP11(−/−) mice displayed an altered electrophoretic mobility caused by impaired N-glycosylation processing, and density gradient centrifugation of kidney homogenate and in vivo protein biotinylation revealed impaired membrane trafficking of PC-1 in these mice. Finally, we showed that the Pkd1(+/−) background increased the severity of cystogenesis in AQP11(−/−) mouse kidneys, indicating that PC-1 is involved in the mechanism of cystogenesis in AQP11(−/−) mice. Additionally, the primary cilia of proximal tubules were elongated in AQP11(−/−) mice. Taken together, these data show that impaired glycosylation processing and aberrant membrane trafficking of PC-1 in AQP11(−/−) mice could be a key mechanism of cystogenesis in AQP11(−/−) mice.
Use of the Percentage of Free Prostate-Specific Antigen to Enhance Differentiation of Prostate Cancer From Benign Prostatic Disease
Authors: William J. Catalona, Alan W. Partin, Kevin M. Slawin, Michael K. Brawer, Robert C. Flanigan, Anup Patel, Jerome P. Richie, Jean B. deKernion, Patrick C. Walsh, Peter T. Scardino, Paul H. Lange, Eric N. P. Subong, Robert E. Parson, Gail H. Gasior, Kathleen G. Loveland, Paula C. Southwick
Journal: JAMA (1998)

The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use.To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied.Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif).Seven nationwide university medical centers.A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis.A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients.The percentage of free PSA may be used in 2 ways: as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL.Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.
Research Training in Six Selected Internal Medicine Fellowship Programs
Authors: M E Whitcomb, D L Walter
Journal: Annals of Internal Medicine (2000)

Background: Effective July 1997, the American Board of Internal Medicine (ABIM) established a research pathway to certification to encourage research training of general internists and subspecialists. Objective: To document the current status of research training in six selected subspecialty programs, to examine opportunities available for trainees to undertake formal course work, and to report the percentage of subspecialty programs that might accept research pathway fellows. Design: National Study of Graduate Education in Internal Medicine questionnaires from 1996–1997 and 1997–1998. Setting: Programs in internal medicine subspecialties accredited by the Accreditation Council for Graduate Medical Education. Participants: 1163 (84%) and 1094 (79%) directors of internal medicine subspecialty programs in 1996–1997 and 1997–1998, respectively. Measurements: Survey questions on the amount of time fellows usually spend conducting research and available opportunities to pursue course work leading to an advanced degree. Results: On average, during their last year of training, fellows enrolled in infectious disease, nephrology, endocrinology, and rheumatology programs spent 40% to 50% of their time conducting research, whereas fellows in gastroenterology and cardiology spent 25% to 30% of their time conducting research. Compared with programs sponsored by major teaching hospitals, a greater percentage of programs sponsored by academic medical center hospitals planned to accept persons interested in pursuing the new ABIM Research Pathway (28% vs. 8%) and to provide opportunities for fellows to obtain an advanced degree (60% vs. 14%). Conclusions: Few internal medicine subspecialty programs are currently designed to provide adequate research training as defined by the Institute of Medicine and the ABIM.
Proposals for uniform collection of biospecimens from neoadjuvant breast cancer clinical trials: timing and specimen types
Authors: Sherene Loi, W Fraser Symmans, John MS Bartlett, Debora Fumagalli, Laura Van't Veer, John F Forbes, Philippe Bedard, Carsten Denkert, JoAnne Zujewski, Giuseppe Viale, Lajos Pusztai, Laura J Esserman, Brian R Leyland-Jones
Journal: The Lancet Oncology (2011)
Highly Conserved <i>Neisseria meningitidis</i> Surface Protein Confers Protection against Experimental Infection
Authors: Denis Martin, Nathalie Cadieux, Josée Hamel, Bernard R. Brodeur
Journal: The Journal of Experimental Medicine (1997)

A new surface protein, named NspA, which is distinct from the previously described Neisseria meningitidis outer membrane proteins was identified. An NspA-specific mAb, named Me-1, reacted with 99% of the meningococcal strains tested indicating that the epitope recognized by this particular mAb is widely distributed and highly conserved. Western immunoblotting experiments indicated that mAb Me-1 is directed against a protein band with an approximate molecular mass of 22,000, but also recognized a minor protein band with an approximate molecular mass of 18,000. This mAb exhibited bactericidal activity against four meningococcal strains, two isolates of serogroup B, and one isolate from each serogroup A and C, and passively protected mice against an experimental infection. To further characterize the NspA protein and to evaluate the protective potential of recombinant NspA protein, the nspA gene was identified and cloned into a low copy expression vector. Nucleotide sequencing of the meningococcal insert revealed an ORF of 525 nucleotides coding for a polypeptide of 174 amino acid residues, with a predicted molecular weight of 18,404 and a isoelectric point of 9.93. Three injections of either 10 or 20 microg of the affinity-purified recombinant NspA protein efficiently protected 80% of the mice against a meningococcal deadly challenge comparatively to the 20% observed in the control groups. The fact that the NspA protein can elicit the production of bactericidal and protective antibodies emphasize its potential as a vaccine candidate.
An experimental renal acidification defect in patients with hereditary fructose intolerance
Authors: R. Curtis Morris
Journal: Journal of Clinical Investigation (1968)

In adult patients with hereditary fructose intolerance (HFI) fructose induces a renal acidification defect characterized by (a) a 20-30% reduction in tubular reabsorption of bicarbonate (T HCO(3) (-)) at plasma bicarbonate concentrations ranging from 21-31 mEq/liter, (b) a maximal tubular reabsorption of bicarbonate (Tm HCO(3) (-)) of approximately 1.9 mEq/100 ml of glomerular filtrate, (c) disappearance of bicarbonaturia at plasma bicarbonate concentrations less than 15 mEq/liter, and (d) during moderately severe degrees of acidosis, a sustained capacity to maintain urinary pH at normal minima and to excrete acid at normal rates. In physiologic distinction from this defect, the renal acidification defect of patients with classic renal tubular acidosis is characterized by (a) just less than complete tubular reabsorption of bicarbonate at plasma bicarbonate concentrations of 26 mEq/liter or less, (b) a normal Tm HCO(3) (-) of approximately 2.8 mEq/100 ml of glomerular filtrate, and (c) during acidosis of an even severe degree, a quantitatively trivial bicarbonaturia, as well as (d) a urinary pH of greater than 6. That the fructose-induced renal acidification defect involves a reduced H(+) secretory capacity of the proximal nephron is supported by the magnitude of the reduction in T HCO(3) (-) (20-30%) and the simultaneous occurrence and the persistence throughout administration of fructose of impaired tubular reabsorption of phosphate, alpha amino nitrogen and uric acid.A reduced H(+) secretory capacity of the proximal nephron also appears operative in two unrelated children with hyperchloremic acidosis, Fanconi's syndrome, and cystinosis. In both, T HCO(3) (-) was reduced 20-30% at plasma bicarbonate concentrations ranging from 20-30 mEq/liter. The bicarbonaturia disappeared at plasma bicarbonate concentrations ranging from 15-18 mEq/liter, and during moderate degrees of acidosis, urinary pH decreased to less than 6, and the excretion rate of acid was normal.
EuroCMR (European Cardiovascular Magnetic Resonance) Registry
Authors: Oliver Bruder, Steffen Schneider, Detlef Nothnagel, Thorsten Dill, Vinzenz Hombach, Jeanette Schulz-Menger, Eike Nagel, Massimo Lombardi, Albert C. van Rossum, Anja Wagner, Juerg Schwitter, Jochen Senges, Georg V. Sabin, Udo Sechtem, Heiko Mahrholdt
Journal: Journal of the American College of Cardiology (2009)
DNA immunization of neonates induces immunity despite the presence of maternal antibody.
Authors: E Manickan, Z Yu, B T Rouse
Journal: Journal of Clinical Investigation (1997)

Neonatal animals were not considered as suitable vaccine recipients either because of immune immaturity or because passively delivered antibody interferes with immune induction. In this report, we evaluated the response of neonatal mice to immunization with naked DNA encoding a herpes simplex virus (HSV) protein, and determined if maternally derived HSV antibody interfered with immunogenicity. Our results show that neonatal mice develop effective humoral and T cell responses after immunization with either DNA or inactivated vaccines. The nature of the responses to HSV immunization, however, was more Th2-like in neonates than in adults. Whereas neonatal mice from HSV-naive mothers responded well to both DNA and inactivated vaccines, only DNA immunization induced effective immunity in neonates born to immune mothers. Our results indicate that DNA vaccines might provide a useful means of immunizing young animals that still possess high levels of potentially interfering maternal antibody.