tbuckley/cabot-search huggingface dataset:
Upregulation of aquaporin-2 water channel expression in chronic heart failure rat.
Authors: D L Xu, P Y Martin, M Ohara, J St John, T Pattison, X Meng, K Morris, J K Kim, R W Schrier
Journal: Journal of Clinical Investigation (1997)

Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.
Comparative hemodynamic effects of chewable isosorbide dinitrate and nitroglycerin in patients with congestive heart failure.
Authors: E Mikulic, J A Franciosa, J N Cohn
Journal: Circulation (1975)

Vasodilators are known to be effective in improving the hemodynamics of congestive heart failure by increasing cardiac output and reducing left ventricular filling pressure (LVFP). Long acting agents are needed to augment the practicality and availability of chronic vasodilator therapy. In the present study the vascular effects of chewable isosorbide dinitrate (CHIS), sublingual nitroglycerin (NTG) and placebo (P) were compared in eight patients with high LVFP due to heart failure. Patients with LVFP (pulmonary wedge pressure) over 14 mm Hg were given CHIS, 10 mg, NTG, 0.6 mg, and P, two chewable tablets, in random fashion. Heart rate (HR), blood pressure (BP) and LVFP were monitored for three hours after each drug. HR was not significantly affected by any drug, although it rose slightly after NTG and fell after CHIS. Significant reduction of BP occurred only after NTG, with peak effect at five minutes, but lasting only 15 minutes. NTG reduced LVFP 5.1 mm Hg (19.5%, P, less than 0.05), at peak effect, but LVFP was no longer significantly lower by 20 minutes after NTG. After CHIS, LVFP fell significantly within five minutes, reached a peak reduction of 8.6 mm Hg (32;7%, P less than 0.01) at 15 minutes, and remained significantly lower through three hours. Thus CHIS provides a nitrate action of rapid onset and sustained effect that may be useful for chronic vasodilator therapy of heart failure.
Fundamentals of Vascular Grafting
Authors: Theodore B. Massell
Journal: JAMA (1964)

In November of 1962 a two-day symposium on vascular grafting was held at the Downstate Medical Center of New York University under the auspices of the editors of this volume. The papers presented at this meeting, representing the work of almost every significant contributor to knowledge of this field, have been collected and published a little more than a year later. By putting the material into book form so soon after the original presentation, the editors have been able to avoid the expression of obsolete or outdated ideas, a problem so often encountered in the publication of a medical monograph. On the other hand, too many of the chapters (or papers) are completely devoid of bibliography. Perhaps a less hurried preparation might have rendered unnecessary this omission. The entire field of vascular grafting has been covered from the academic to the practical. The various authors have presented essentially all the
Surgery--before and after penicillin.
Authors: C Butler
Journal: BMJ (1979)

When I was appointed to the staff of the London Hospital in 1937 it was customary for the junior assistant surgeon to take charge of the septic block, which consisted of two wards with some 50 beds.At that time, considerable interest in the treatment of surgical infections had already been aroused in Britain- firstly, with the introduction of Prontosil, and, later on, the sulphonamides.Further advances were confidently expected.Nevertheless, despite great achievements in treating streptococcal infections, no comparable advance was made in those infections that were due to Staphylococcus aureus-although many new drugs, notably sulphathiazole, were partially successful.I was interested in the problem as soon as I went to the London because the patients attending the hospital were unique, in that most of them, at that time, came from the East End of London, an area where malnutrition and disease were much in evidence.The average annual admission of cases of
Arteriovenous haemofiltration: a recent advance in the management of renal failure.
Authors: N J Dodd, R M O'Donovan, D N Bennett-Jones, P B Rylance, M Bewick, V Parsons, M J Weston
Journal: BMJ (1983)

Twenty five patients with oliguric renal failure were treated by a combination of continuous arteriovenous haemofiltration and intermittent haemodialysis over 18 months. Haemofiltration was given for a mean of 6.6 days and the mean filtration volume was 6.0 1/day. Fourteen of the 25 patients survived beyond two months after the period of oliguria. Haemofiltration proved to be a simple and effective method of fluid removal; it allowed maintenance of stable fluid balance and permitted optimum nutrition during prolonged oliguria.
Sex and Gender: On the Development of Masculinity and Femininity
Authors: Donald W. Goodwin
Journal: JAMA (1968)

"Sex" in this title refers to biological sex, "gender" to the concept that people have of themselves as male or female. How sex relates to gender—or, more precisely, fails to relate—is the subject of the book. The author is a psychoanalyst with ten year's experience of treating patients with congenital sexual anomalies and those of normal biological endowment whose "genders" are awry. The latter consist mainly of individuals who dress like the opposite sex (transvestities) and those who ardently desire to be the opposite sex (transexuals), even to the point of seeking surgical manipulation to that end. Stoller marshals an impressive array of clinical evidence to indicate that psychological sex is largely independent of biological sex—at least in humans. Early parental influences are held to be the decisive factor in molding gender identity, and the author, true to his professional background, explains these influences largely in freudian terms, with a
De novo minor status epilepticus of late onset presenting as stupor.
Authors: D E Bateman, J C O'Grady, C J Willey, B P Longley, D D Barwick
Journal: BMJ (1983)

available suggests that convulsions are the only serious complication of acute zimeldine overdosage.[Sales of zimeldine in all countries were discontinued by Astra Pharma- ceuticals in September 1983 because of the company's concern about reports of serious neurological side effects including the Guillain Barr6 syndrome.]I Dawling S, Braithwaite RA.Simplified method for monitoring tricyclic antidepressant therapy using gas-liquid chromatography with nitrogen detection.7
The Counseling Practices of Internists
Authors: Charles E. Lewis, Carolyn Clancy, Barbara Leake, J. Sanford Schwartz
Journal: Annals of Internal Medicine (1991)

To determine the counseling practices of a group of internists in the areas of smoking, exercise, and alcohol and seat belt use, and to determine the associations among physicians' personal health habits and their counseling practices.A random stratified sample of members and fellows of the American College of Physicians in 21 regions selected to represent all areas of the United States. Because of the relatively small proportion of women in this group, they were oversampled.Physicians' practices.One thousand three hundred and forty-nine internists (members or fellows of the College) returned questionnaires, for a response rate of 75%; 52% defined themselves as general internists.A questionnaire was used to obtain information on internists' use of cigarettes, alcohol, and seat belts and their level of physical activity. Data were obtained on the indications used for counseling and the aggressiveness of counseling about each of these four habits.Bivariate and logistic regression analyses were used to compare the tendencies of internist subgroups both in using various indications for counseling and in the thoroughness of counseling. Generalists were more likely than specialists to counsel at least once all patients who were at risk and to be more aggressive in counseling. Ninety percent of respondents counseled all of their patients who smoked, but 64.5% never discussed the use of seat belts. Only 3.8% of these internists currently smoked cigarettes, 11.3% drank alcohol daily, 38.7% were extremely or quite active, and 87.3% used seat belts all or most of the time. Among men internists, for every habit except alcohol use, personal health practices were substantially associated with counseling patients; for example, nonsmoking internists were more likely to counsel smokers, and very physically active internists were more likely to counsel about exercise. Among women internists, being very physically active was associated with counseling more patients about exercise and alcohol use.The low level of self-reported counseling among these internists suggests that further emphasis on training in these skills is needed. The association between personal and professional practices suggests that medical schools and housestaff training programs should support health promotion activities for future internists.
<i>Science Translational Medicine</i> Podcast: 30 June 2010
Authors: Victoria E. Boegh, Gary L. Hecimovich, Annalisa M. VanHook
Journal: Science Translational Medicine (2010)

A conversation with Gary L. Hecimovich and Victoria E. Boegh from Deloitte Tax LLP on the new $1 billion program created by the U.S. Patient Protection and Affordable Care Act.
Abstract 5129: Role of PRKD2 in HSP90 inhibition-mediated suppression of cancer growth
Authors: Ninel Azoitei, Kristina Diepold, Felicitas Genze, Arefeh Rouhi, Susanne Brobovich, Stefan Froehling, Gabriela Chiosis, Cornelia Brunner, Johan van Lint, Marcus Cronauer, Claudia Scholl, Thomas Seufferlein
Journal: Cancer Research (2014)

Abstract In various types of malignancies, conventional forms of therapy such as surgery, radiation and chemotherapy are often ineffective. In the past decade, a convergence of scientific and technological advances has enabled the identification of molecular targets and signaling pathways specific to cancer cells, resulting in therapies with enhanced selectivity and efficacy and reduced toxicity. Protein kinases represent such molecular targets. We have recently shown that PRKD2 is a crucial regulator of tumor cell - endothelial cell communication in gastrointestinal tumors and demonstrated the kinase to be a novel regulator of glioblastoma growth. Here we report that HSP90/Cdc37 chaperone complex binds to and stabilizes PRKD2 in human cancer cells. RNAi-mediated ablation of HSP90 expression but also the pharmacological inhibition of the chaperone with two independent inhibitors induced degradation of PRKD2 in a broad range of human cancer cell lines and in vivo. Treatment of various cancer cell lines with proteasome inhibitors such as MG-132 or Bortezomib, followed by incubation with HSP90 inhibitors rescued the PRKD2 levels to the detergent-insoluble fraction suggesting that degradation of the kinase follows the proteasomal pathway. Kinetic experiments conducted with chaperone inhibitors demonstrated that PRKD2 was degraded in a time- and dose-dependent manner and this degradation was associated with the activation of the apoptotic programme both in vitro and in vivo. Furthermore, ectopic expression of the kinase protected cancer cells from the apoptotic effects of HSP90 abrogation suggesting PRKD2 as a protein whose depletion mediates the sensitivity of tumor cells to chaperone inhibition. Altogether, these findings 1) propose PRKD2 ablation through HSP90 inhibition as a potential therapeutic strategy with immediate implementation, 2) reveal the kinase as a crucial modulator of HSP90-mediated apoptotic effects and 3) promote the intensification of designing specific PRKD2 inhibitors and their implementation in targeted therapy in human cancer. Citation Format: Ninel Azoitei, Kristina Diepold, Felicitas Genze, Arefeh Rouhi, Susanne Brobovich, Stefan Froehling, Gabriela Chiosis, Cornelia Brunner, Johan van Lint, Marcus Cronauer, Claudia Scholl, Thomas Seufferlein. Role of PRKD2 in HSP90 inhibition-mediated suppression of cancer growth. [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 5129. doi:10.1158/1538-7445.AM2014-5129
Production of a cytokine with interleukin 3-like properties and cytokine-dependent proliferation in human autologous mixed lymphocyte reaction.
Authors: R Suzuki, S Suzuki, T Takahashi, K Kumagai
Journal: The Journal of Experimental Medicine (1986)

The autologous mixed lymphocyte reaction (AMLR) was assayed in a medium containing fresh autologous serum, by using nylon-adherent stimulator cells and nonadherent responder T cells, which were prepared from human peripheral blood mononuclear cells in the absence of fetal calf serum (FCS) to avoid any sensitization to xenogeneic protein antigens. DNA replication without a background proliferative response was induced by stimulator cells in the responder cells. The addition of monoclonal anti-HLA-DR antibody to the culture or treatment of the responder cells with complement plus anti-T4 but not anti-T8 monoclonal antibody suppressed the AMLR, suggesting that this specific AMLR involves an interaction between HLA-DR antigens and helper/inducer T cells. Regardless of this specific DNA replication, the AMLR generated no production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), both of which could be found in the allogeneic (allo) MLR. In addition, DNA replication in the AMLR was not inhibited by the addition of specific antisera for IL-2 and IFN-gamma, both of which significantly inhibited the DNA replication in allo-MLR. The AMLR was accompanied by production of a soluble factor, which could stimulate the proliferation of murine interleukin 3 (IL-3)-dependent cell line 32Dcl but not the proliferation of IL-2-dependent cell lines. This factor was also found to be responsible for proliferation of responder nonadherent cells in the AMLR. It strongly stimulated bone marrow cells, as did the murine IL-3. The factor had an Mr range, as determined by gel filtration, of 15,000-28,000, but it did not bind to fast protein liquid chromatography (FPLC)-MonoQ column. Thus, the factor is distinguishable from IL-2 in physicochemical or biological properties, but similar to murine IL-3. These results suggest that the human AMLR may be primarily a phenomenon in which non-T cells mediated by the HLA-DR antigens on the cell stimulate helper/inducer T cells to produce a lymphokine with IL-3-like properties, but no IL-2, which in turn stimulates the factor-dependent cells to proliferate.
Comparison of the handling of norepinephrine in the myocardium of adult and old rats
Authors: C. J. LIMAS
Journal: Cardiovascular Research (1975)

The handling of norepinephrine was compared in the myocardium of adult and old rats. Endogenous norepinephrine levels were significantly lower in the hearts of old animals. Following intravenous injection of 3H-norepinephrine [3H-NE] the initial uptake was slightly higher in the old animals; subsequently, however, there was a more pronounced and prolonged fall in 3H-NE specific activity in the myocardium of the old rats. The increased turnover rate was associated with normal catecholamine synthesis. Studies of the subcellular distribution of 3H-NE showed an inability of the myocardium from ageing rats to retain norepinephrine in the storage granules with subsequent loss of the soluble fraction.
Hospitals urged to review how far key emergency staff live from work
Authors: R. Dobson
Journal: BMJ (2009)

The National Patient Safety Agency has urged hospitals to look at how long it takes on-call staff to respond to emergencies, and how far away they live from their main place of work.

The agency has also asked whether there have been any serious near miss incidents out of hours owing to delays to emergency surgery or diagnostic procedures.

The requests were prompted by an agency advisory note, or “signal,” which was triggered by a coroner’s letter reviewed by the agency’s National Reporting and Learning Service. The review identified …
Another antibody in myasthenia gravis sera?
Authors: Jean McCann
Journal: JAMA (1982)

Plasmapheresis should be attempted in severe refractory cases of myasthenia gravis even when acetylcholine receptor antibody (AChRab) levels are not elevated in the serum. This is because another form of antibody may be involved in some cases of this disease, Peter Kornfeld, MD, told<i>JAMA</i>MEDICAL NEWS, and there could be still others. Kornfeld, a speaker at the World Neurology Congress in Kyoto, Japan, said he has used plasmapheresis in seven patients having normal AChRab levels with good results. This discovery is the latest from a series of studies in which Kornfeld and his group at the Myasthenia Gravis Clinic at Mount Sinai Medical Center in New York have been studying the role of plasmapheresis in myasthenia gravis patients who do not respond to thymectomy, corticosteroids, or anticholinesterase drugs. In an earlier series of 16 patients with refractory, generally severe myasthenia gravis, Kornfeld got an excellent clinical response in 12
Abstract 3139: Identification and functional studies of p53 mutants detected in breast cancers after chemotherapy treatment.
Authors: Johanna Huun, Elisabet O. Berge, Johan R. Lillehaug, Per Eystein Lonning, Stian Knappskog
Journal: Cancer Research (2013)

Abstract Background: Approximately 4300 different TP53 mutations have been reported in human cancers. TP53 mutations, in particular those affecting the L2/L3 domains, are associated with resistance to anthracycline or mitomycin treatment in breast cancer patients. While many mutations have been characterised functionally, novel TP53 mutations are continuously reported. Here, we characterise 10 p53 protein variants encoded by mutated TP53 (5 within and 5 outside L2/L3) detected in locally advanced or metastatic breast cancers. Each tumour was previously characterised for response to therapy, allowing comparison between in vivo and in vitro findings. Methods: Mutated p53 variants were analysed for their ability to oligomerise with the wild-type protein and their subcellular localisation by immunoprecipitation and immunofluorescence, respectively. Their ability to induce transcription of target genes was determined by qPCR. Cellular growth rate, apoptosis and senescence were monitored by WST-1, TUNEL and beta-galactosidase assays, respectively. Results: Immunoprecipitation assays revealed each mutant protein to retain binding capacity for wild-type p53, thus potentially acting in a dominant negative manner. Even though each p53 variant located predominantly in the nucleus, the percentage of cells with only nuclear p53 localisation varied between 60-90%. None of the p53 variants were able to induce target genes to levels similar to wild-type p53, nor where they able to reduce cellular growth rate, induce apoptosis or senescence similar to wild-type p53 after anthracycline treatment in vitro. Conclusions/General Significance: Our data add further information characterising the effects of somatic TP53 mutations on p53 protein function and anthracycline resistance in breast cancer. Citation Format: Johanna Huun, Elisabet O. Berge, Johan R. Lillehaug, Per Eystein Lonning, Stian Knappskog. Identification and functional studies of p53 mutants detected in breast cancers after chemotherapy treatment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3139. doi:10.1158/1538-7445.AM2013-3139
Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.
Authors: J D Horton, J A Cuthbert, D K Spady
Journal: Journal of Clinical Investigation (1993)

The concentration of LDL in plasma is strongly influenced by the amount and the type of lipid in the diet. Recent studies in the hamster have shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liver. To investigate the mechanistic basis of this effect, rates of receptor-dependent LDL transport in the liver were correlated with LDL receptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fed safflower oil at all levels of cholesterol intake (26, 53, and 61% lower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). These fatty acid-induced changes in hepatic LDL receptor activity were accompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level.
Hydronephrosis in Infants and Children
Authors: John A. Askin
Journal: JAMA (1968)

To the Editor:—  In the very excellent report, Hydronephrosis in Infants and Children, by Uson, et al (205: 323, 1968) two of the clinical observations, which were emphasized, merit further comment.   Most abdominal, abnormal masses in children are due to kidney lesions. In our report,  for Excretory Urology in Children, (Pediatrics 20:1033, 1957), 71% of the children with abnormal abdominal masses (30 of 42 patients) had kidney disease.  The increased number of children with hydronephrosis admitted to Columbia Presbyterian Medical Center was undoubtedly due to the increased awareness by the pediatricians of the possible presence of an abnormality of the excretory tract. The years 1940 to 1945 mark the era when pediatricians were first becoming aware of the fact that a congenital anomaly of the excretory system may exist without the presence of white or red blood cells in the urine.   Indications such as (1) congenital malformations