tbuckley/cabot-search huggingface dataset:
Intracellular pH regulation in rabbit renal medullary collecting duct cells. Role of chloride-bicarbonate exchange.
Authors: M L Zeidel, P Silva, J L Seifter
Journal: Journal of Clinical Investigation (1986)

The renal medullary collecting duct (MCD) secretes protons into its lumen and HCO3 into its basolateral space. Basolateral HCO3 transport is thought to occur via Cl/HCO3 exchange. To further characterize this Cl/HCO3 exchange process, intracellular pH (pHi) regulation was monitored in freshly prepared rabbit outer MCD cells. Cells were separated by protease digestion and purified by Ficoll gradient centrifugation. pHi was estimated fluorometrically using the entrapped intracytoplasmic pH indicator, 6-carboxyfluorescein. Cells were preincubated in bicarbonate-containing solutions and then abruptly diluted into bicarbonate-free media. The MCD cell pHi response to abrupt removal of CO2/HCO3 included an initial alkalinization due to rapid CO2 efflux, followed by an acidification due to HCO3 efflux and a gradual recovery to the resting pHi of 7.24 +/- 0.06 partly due to the action of a plasma membrane H+-ATPase. The initial alkalinization required a CO2/HCO3 gradient and did not occur in the presence of acetazolamide. The acidification phase required intracellular HCO3 and extracellular Cl, which was consistent with a Cl/HCO3 exchange. MCD HCO3 efflux exhibited saturable kinetics for extracellular Cl, with a Michaelis constant (Km) of 29.9 +/- 7.7 mM. HCO3 efflux also exhibited preference for halides over NO3, SCN, and gluconate, and striking sensitivity to disulfonic stilbene and acetazolamide inhibition, with an apparent K1 of 5 X 10(-7) M for DIDS. The final pHi recovery required intracellular ATP, which indicated that Cl/HCO3 and H+-ATPase activities are present in the same cells in these suspensions. The results provide direct evidence for MCD Cl/HCO3 exchange and describe some of the properties of this transport process.
Underreporting of mortality from RhD haemolytic disease in Scotland and its implications: retrospective review
Authors: C. R Whitfield, A. Raafat, S. J Urbaniak
Journal: BMJ (1997)

Clarke et al surveyed the decline in RhD haemolytic disease in England and Wales from 1977–92 by reviewing the statistics of the Office of Population Censuses and Surveys; during that time deaths attributable to RhD haemolytic disease had fallen from 18.4 to 1.3 per 100 000 live births.1 We surveyed RhD alloimmunisation in mothers resident in Scotland between 1987 and 91 and confirmed that fetal loss from RhD haemolytic disease was greater than that listed by the General Register Office in Scotland. Underreporting has serious implications for recognising, understanding, and preventing this potentially lethal disease.

Data on deaths attributable to RhD haemolytic disease during 1987–91 were obtained from: death certificates; details of pregnancies in Scottish residents who had antibody to RhD antigen and were managed at …
Influence of Sex Hormones on Plasma Endothelin Levels
Authors: Kees H. Polderman
Journal: Annals of Internal Medicine (1993)

To determine whether a sex-associated difference in endothelin levels exists and to assess whether this difference is mediated by sex hormones.Initial survey in healthy persons, followed by a nonrandomized intervention.A university teaching hospital.Twenty-three healthy men, 29 healthy women, 20 pregnant women, and 12 male-to-female and 13 female-to-male transsexual patients.Plasma levels of endothelin were first assessed in healthy men, healthy women, and pregnant women; subsequently, endothelin levels were determined in male-to-female and female-to-male transsexual patients both before and during cross-gender hormone treatment. This treatment involves administration of testosterone esters to women and of ethynylestradiol and cyproterone acetate to men.Endothelin levels were higher in men than in women (5.9 +/- 1.2 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). Endothelin levels were lower in pregnant women than in age- and sex-matched nonpregnant controls (2.19 +/- 0.73 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). In 12 male-to-female transsexuals treated with estradiol and the progestational agent cyproterone acetate, endothelin levels decreased from 8.1 +/- 3.0 to 5.1 +/- 2.0 pg/mL (P < 0.01). In 13 female-to-male transsexuals treated with testosterone, endothelin levels increased from 6.2 +/- 1.1 to 7.8 +/- 1.2 pg/mL (P < 0.01).Sex hormones may modulate plasma endothelin levels, with male hormones raising levels and female hormones lowering them. This finding may be important in explaining sex-associated differences in susceptibility to atherosclerotic cardiovascular disease.
Why, Oh Why, Did He Die?
Authors: Ruth M. Barrett
Journal: JAMA (1964)

<h3>To the Editor:—</h3> The editorial, "Why, Oh Why, Did He Die?" by Dr. Sigmund Wilens in the March 28 issue ofThe Journal(<b>187</b>:1020) is a most accurate report of the pathologist's dilemma. As a medical examiner, I have frequently used the term "congestion of viscera" on a death certificate. In the Westchester County Medical Examiner's Office this expression is used simply as a delaying tactic. New York State law requires filing of a death certificate within 72 hours after the knowledge of a death. The time gained while this certificate is being filed can then be used for histological and chemical investigation. All of our certificates filed with the cause of death listed as "congestion of viscera" are altered by a subsequent correcting certificate. Herein lies the moment of truth. Dr. Wilens wondered if medical examiners don't have "cause of death trouble." We do. Most of the congestion
CT2—The Clinical Trials Control Tower: Overcoming Barriers to Opening Oncology Clinical Trials
Authors: Anthea L. Hammond, Edmund K. Waller, Lee B. Finkelstein
Journal: Journal of Clinical Oncology (2007)

interest, and applaud the authors’ meticulous efforts and candor in illuminating the barriers that exist to opening oncology clinical trials in an academic health center setting. As a matrix cancer center reliant on interaction with other departments to execute the opening of clinical trials, the Winship Cancer Institute at Emory University (Atlanta, GA) realizes similar challenges to those reported at Vanderbilt. Several of these steps are difficult to circumvent in an academic health care center, and we believe that these processes make it more challenging for academic centers to attract pharmaceutical industry-sponsored clinical trials. We fully agree with the authors that overcoming the barriers to opening oncology clinical trials “is of critical importance for maintenance of core oncology research capabilities in the United States.” 1 At the Winship Cancer Institute, we have begun to develop and implement a method to improve the efficiency with which we open clinical trials. We have termed this process the CT2, the clinical trials control tower, since the management of clinical trials is somewhat akin to that of airport traffic, a process that has been described as managing controlled chaos. We have employed a program coordinator to electronically track the progress of each protocol from inception to closure, much like the tracking of moving aircraft on a radar screen. This control tower monitors and manages the functions of the key parties involved in the initiation of each protocol (the study investigator, the clinical trials office, other institutional departments and committees, and the study sponsor), and provides the communication within and between these parties necessary to streamline the progress of each protocol through the clinical trial initiation process. Clinical research can only succeed in increasing efficiency if we identify stop-gaps in the current process, and learn how to improve these procedures by critically evaluating their current quality and efficiency. Our tracking efforts show that we experience similar obstacles to those seen by the Vanderbilt Cancer Center (Nashville, TN) and its affiliates. In conclusion, we fully concur with the findings of this enlightening study regarding the barriers that exist in academia to opening oncology clinical trials. We believe academic institutions offer outstanding resources for the pharmaceutical industry to conduct clinical trials, but that we must strive to function more efficiently to attract the business of pharmaceutical sponsors. We hope that our CT2 model will facilitate a leaner process that will expedite the opening of both industry-sponsored and investigator-initiated clinical trials, ultimately providing more treatment options for cancer patients.
Theophylline and Atrioventricular Block
Authors: Barry D. Bertolet
Journal: Annals of Internal Medicine (1996)

Letters1 September 1996Theophylline and Atrioventricular BlockBarry D. Bertolet, MD and Luiz Belardinelli, MDBarry D. Bertolet, MDUniversity of Florida, Gainesville, FL 32610-0277Search for more papers by this author and Luiz Belardinelli, MDUniversity of Florida, Gainesville, FL 32610-0277Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-5-199609010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Weiss for his interest in our recent article. Theophylline was to be administered at a rate of 100 mg/min until conversion to normal sinus rhythm occurred or until a maximum of 250 mg was administered. As noted by Dr. Weiss, although two patients converted to normal sinus rhythm after receiving 100 mg of theophylline, a total of 250 mg was administered by the treating physicians. It is now our practice, however, to empirically administer 250 mg of theophylline as a slow intravenous bolus when hemodynamically significant atrioventricular block occurring as a complication of myocardial infarction ... Author, Article, and Disclosure InformationAuthors: Barry D. Bertolet, MD; Luiz Belardinelli, MDAffiliations: University of Florida, Gainesville, FL 32610-0277 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1996Volume 125, Issue 5Page: 421KeywordsAdenosineBradycardiaElectrophysiological techniquesHeart failureMyocardial infarctionPatients ePublished: 15 August 2000 Issue Published: 1 September 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Recent treatment with H2 antagonists and antibiotics and gastric surgery as risk factors for salmonella infection
Authors: R K Neal, O S Brij, B C R Slack, J C Hawkey, R F A Logan
Journal: BMJ (1994)

Experimental evidence shows that gastric acid protects against enteric infections,1,2 and patients who have had gastric surgery seem to be more susceptible to salmonella infection.3,4 Whether H2 antagonists are also associated with salmonella infection is not known, although diarrhoea is a recognised side effect. Statutory notifications of salmonella infection have increased in recent years and the use of H2 antagonists has become widespread, suggesting that suppression of acid by these drugs may have been contributory. We conducted a case-control study to assess whether H2 antagonists are associated with salmonella infection.

From March 1990 to September 1992, 218 notified cases of salmonella infection, confirmed by faecal culture, occurred in people aged >=45 in the Nottingham area. Thirty cases were excluded because the …
FURTHER STUDIES ON THE INFLUENCE OF TESTICLE EXTRACT UPON THE EFFECT OF TOXINS, BACTERIA, AND VIRUSES, AND ON THE SHWARTZMAN AND ARTHUS PHENOMENA
Authors: F. Duran-Reynals
Journal: The Journal of Experimental Medicine (1933)

The lesions produced by the Shwartzman and Arthus phenomena, as well as those produced by bacterial toxin and foreign sera in the normal rabbit, are spread by testicle extract over a larger area than would normally take place. With this spreading of the lesions there is a definite reduction in their intensity. Lesions produced by invasive strains of staphylococcus at high dilutions or non-invasive staphylococci at moderate dilutions are definitely lessened in severity or even suppressed by the spreading action of testicle extract. Virus lesions are consistently enhanced by the spreading factor regardless of the dilution.
Reliability of a History of Previous Varicella Infection in Adults
Authors: Mark R. Wallace
Journal: JAMA (1997)

Apparent second episodes of varicella are reported in immunocompetent hosts, but laboratory confirmation of prior immune status has rarely been possible.To evaluate adult patients with varicella who claimed to have had previous varicella to determine whether they had true second episodes or primary cases with inaccurate clinical histories.Adult subjects with varicella who enrolled in an antiviral treatment trial were interviewed about a history of varicella. The clinical course of varicella was documented prospectively in all subjects. Serum samples that predated the acute illness were obtained from the US Navy's central serum storage facility for subjects who reported a previous episode of varicella. These stored samples were tested in parallel by enzyme-linked immunosorbent assay, latex agglutination, and Western blot for IgG antibodies to varicella-zoster virus (VZV).Twenty military personnel with varicella and a history of the disease.A military hospital in San Diego, Calif.Presence or absence of antibodies to VZV.Twenty (10.8%) of 184 adults with serologically confirmed acute varicella reported a prior history of varicella. The clinical course of these 20 patients did not differ from those with no history of varicella. Serum samples that had been collected a mean of 12.4 months (median, 12 months; range, 3 days to 34 months) before the incident episode were available for 19 subjects. All 19 serum samples lacked IgG antibodies to VZV.A history of previous varicella infection in adults with varicella may not be reliable. True second episodes of varicella are probably rare in immunocompetent adults.
Smooth Muscle Cell α <sub>2</sub> δ-1 Subunits Are Essential for Vasoregulation by Ca <sub>V</sub> 1.2 Channels
Authors: John P. Bannister, Adebowale Adebiyi, Guiling Zhao, Damodaran Narayanan, Candice M. Thomas, Jessie Y. Feng, Jonathan H. Jaggar
Journal: Circulation Research (2009)

Rationale : Voltage-dependent L-type (Ca V 1.2) Ca 2+ channels are a heteromeric complex formed from pore-forming α 1 and auxiliary α 2 δ and β subunits. Ca V 1.2 channels are the principal Ca 2+ influx pathway in arterial myocytes and regulate multiple physiological functions, including contraction. The macromolecular composition of arterial myocyte Ca V 1.2 channels remains poorly understood, with no studies having examined the molecular identity or physiological functions of α 2 δ subunits. Objective : We investigated the functional significance of α 2 δ subunits in myocytes of resistance-size (100 to 200 μm diameter) cerebral arteries. Methods and Results : α 2 δ-1 was the only α 2 δ isoform expressed in cerebral artery myocytes. Pregabalin, an α 2 δ-1/-2 ligand, and an α 2 δ-1 antibody, inhibited Ca V 1.2 currents in isolated myocytes. Acute pregabalin application reversibly dilated pressurized arteries. Using a novel application of surface biotinylation, data indicated that &gt;95% of Ca V 1.2 α 1 and α 2 δ-1 subunits were present in the arterial myocyte plasma membrane. α 2 δ-1 knockdown using short hairpin RNA reduced plasma membrane-localized Ca V 1.2 α 1 subunits, caused a corresponding elevation in cytosolic Ca V 1.2 α 1 subunits, decreased intracellular Ca 2+ concentration, inhibited pressure-induced vasoconstriction (“myogenic tone”), and attenuated pregabalin-induced vasodilation. Prolonged (24-hour) pregabalin exposure did not alter total α 2 δ-1 or Ca V 1.2 α 1 proteins but decreased plasma membrane expression of each subunit, which reduced myogenic tone. Conclusions : α 2 δ-1 is essential for plasma membrane expression of arterial myocyte Ca V 1.2 α 1 subunits. α 2 δ-1 targeting can block Ca V 1.2 channels directly and inhibit surface expression of Ca V 1.2 α 1 subunits, leading to vasodilation. These data identify α 2 δ-1 as a novel molecular target in arterial myocytes, the manipulation of which regulates contractility.
THE CRIMINAL RESPONSIBILITY OF INSANE PERSONS.CHAIRMAN'S ADDRESS BEFORE THE SECTION ON NERVOUS AND MENTAL DISEASES OF THE AMERICAN MEDICAL ASSOCIATION, AT ATLANTIC CITY, JUNE, 1907.
Authors: MORTON PRINCE
Journal: JAMA (1907)

In a trial which has recently aroused the attention of the whole country to a degree unusual even in criminal trials, the failure of the jury to arrive at an agreement regarding the mental responsibility of the defendant has awakened attention to the jury system and the law of criminal responsibility. Doubts have been freely expressed by thinking persons as to the capability of juries to correlate the facts with the law as expounded by the courts, and as to the soundness of the psychologic principles the law formulates. In view of the wide public interest which has been excited, the great diversity of views which have been publicly expressed (for, like the Dreyfus affair, the case has been tried before the great jury of the public as exhaustively as before that of the court), and the importance to society that criminal acts shall not go unpunished where a just
Abstract 1051: EGFR inhibitors attenuate caspase-independent cell death and confer negative effects on cisplatin .
Authors: Hirohito Yamaguchi, Jennifer L. Hsu, Chun-Te Chen, Ying-Nai Wang, Ming-Chuan Hsu, Shih-Shin Chang, Yi Du, How-Wen Ko, Roy S. Herbst, Mien-Chie Hung
Journal: Cancer Research (2013)

Abstract EGFR tyrosine kinase inhibitors (TKIs) have demonstrated exciting results and led to advanced therapy trials in combination with chemotherapy. However, clinical studies have raised an important question why the antagonism between TKI and chemotherapy occurs in lung cancer patients only with wildtype but not mutant EGFR. In this study, we further explored the mechanism through which gefitinib gives rise to the negative effects when combined with cisplatin in wildtype EGFR lung cancer cells. We found that gefitinib inhibited cisplatin-induced caspase-independent cell death (CID) but not caspase-dependent cell death (apoptosis). In wildtype EGFR cells, gefitinib not only inhibited CID but also failed to induce apoptosis and therefore compromising the efficacy of cisplatin. Moreover, inhibition of the EGFR/ERK/AKT pathway by gefinitib activated FOXO3a and subsequently reduced reactive oxygen species (ROS) induced by cisplatin treatment and ROS-mediated CID. To overcome this, we showed that SAHA and erastin, which are known to induce ROS-mediated CID, strongly enhanced the effect of cisplatin in wildtype EGFR cells. Taken together, our findings provide a possible explanation for the previously failed clinical trials as well as a novel insight into future cancer therapy. Citation Format: Hirohito Yamaguchi, Jennifer L. Hsu, Chun-Te Chen, Ying-Nai Wang, Ming-Chuan Hsu, Shih-Shin Chang, Yi Du, How-Wen Ko, Roy S. Herbst, Mien-Chie Hung. EGFR inhibitors attenuate caspase-independent cell death and confer negative effects on cisplatin . [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 1051. doi:10.1158/1538-7445.AM2013-1051
GMC to investigate pathologist who failed to notice adopted infant s injuries
Authors: O. Dyer
Journal: BMJ (2003)

A Northern Ireland assistant state pathologist is to face investigation by the General Medical Council after the pathologist failed to notice several injuries in an adopted toddler who arrived dead at hospital.

Last week an independent review commissioned by Northern Ireland's health minister, Angela Smith, strongly criticised the Craigavon and Banbridge Community Trust, which had responsibility for overseeing the adoption.

The boy, David Filipache, and his twin brother, Samuel, were 11 months old when they were legally adopted in Romania by Geoffrey Briggs, a former missionary, and his wife in July 2000 and brought back …
Disseminated Lupus Erythematosus in the Male
Authors: Bernard H. Pastor, Norman G. Sloane, Harold L. Goldburgh
Journal: New England Journal of Medicine (1951)

MOST reports on disseminated lupus erythematosus have considered it to be a diffuse disease of the collagen system occurring almost exclusively in young adult women. Blount and Barrett,1 reporting a case in a young man, make the observation that the occurrence of this entity in the male is unusual. All the 20 cases reported by Klemperer and his associates2 were in women, and Baehr and Pollack3 state that the most striking characteristic of the disease is its predominant occurrence (95 per cent) in young women. However, 3 of the 12 cases reported by Rose and Pillsbury4 were in males. A . . .
Infant Feeding During Ramadhan
Authors: C. Kirby
Journal: BMJ (1963)

these seasons of respiratory infections, which often occur during the early phases of leukaemia and may draw attention to the leukaemic process.The contrasting patterns between the U.S. and England and Wales, however, may reflect different seasonal distributions associated with enhanced recognition of leukaemia, in- creased host susceptibility to the leuk- aemic process, or specific environmental leukaemogenic factors.-Iam, etc.,
Consequences of potassium recycling in the renal medulla. Effects of ion transport by the medullary thick ascending limb of Henle's loop.
Authors: J B Stokes
Journal: Journal of Clinical Investigation (1982)

The consequences of K recycling and accumulation in the renal medulla were examined by measuring the effect of elevated K concentration on ion transport by the medullary thick ascending limb of Henle's loop. Perfused and bathed in vitro, thick limbs from both mouse and rabbit displayed a graded, reversible reduction of transepithelial voltage after increasing K concentration from 5 to 10, 15, or 25 mM. The effect was reproducible whether osmolality was 328 or 445 mosmol/kg H2O, and whether K replaced Na or choline. Net chloride absorption and transepithelial voltage were reduced by almost 90% when ambient K concentration was 25 mM. When either lumen or bath K was increased to 25 mM, net Na absorption was reduced. There was spontaneous net K absorption when perfusate and bath K concentration was 5 mM. Analysis of transepithelial K transfer after imposition of chemical gradients demonstrated rectification in the absorptive direction. Absorption of K by this segment provides a means to maintain high medullary interstitial concentration. Accumulation of K in the outer medulla, by reducing NaCl absorption, would increase volume flow through the loop of Henle and increase Na and water delivery to the distal nephron. K recycling thus might provide optimum conditions for K secretion by the distal nephron.
Lack of expression of the VHS107 gene family in the lipopolysaccharide-sensitive B cell subset of X-linked immunodeficiency-defective mice.
Authors: D Primi, P A Cazenave
Journal: The Journal of Experimental Medicine (1986)

The expression of the VH T15 gene product was analyzed in the sera and in the supernatants of polyclonally activated B cells of X-linked immunodeficient (xid) mice. We found that defective males, contrary to normal females, do not express the VH T15 gene product even on antibodies devoid of anti-PC specificity. RNA analysis of polyclonally activated cells with VH specific probes revealed that xid-defective B cells do not express the entire S107 or part of the J606 VH family. Members of the J558 family, on the other hand, are equally well expressed among defective males and normal female B cells. These results strongly suggest that VH families are asymmetrically represented among B cell subsets.