tbuckley/cabot-search huggingface dataset:
Influence of Maternal Malaria on Newborn Infants
Authors: H. M. Archibald
Journal: BMJ (1958)

CHILDREN BRDICALJouAL and pathological findings in 11-20% of 500 hospital cases; and Jamnes, Patton, and Heslin (1955) found 71% of original certificates agreeing with necropsy reports in a survey of 1,889 necropsies, but with wide variation within the groups of different diseases, ranging from 21% agreement in the group of arteriosclerotic heart disease to 93% agreement in the group covering tuberculosis.Pohlen and Emerson (1942, 1943) found consistency in diagnosis in 96% of tumours of the heart, compared with 26% in liver tumours, 99% in measles, and 52% in heart disease.In the above 'articles, all of which come from public health departments, there is a tendency to state that errors in registration occur between the few larger groups of causes of death, and that the errors in one direction tend to cancel the others out, making the overall statistics relatively accurate.This seems to be an unfortunate argument, as it would appear to give the published figures false accuracythe type of accuracy obtained by drawing random diagnoses out of a hat-and minimize the danger of arguing from any of the registrar's statistics.In assessing the accuracy of certification, any comparison made must be between the cause of death as originally certified and the cause of death after survey of all information obtained by clinical and necropsy examination.Inaccuracies in certification arise in two ways: first; a failure to record accurately the knowledge available at the time of death-that is, negligent certification; and, secondly, the inadequacy of the knowledge available at the time of certification.In a teaching hospital, where every child, particularly an ill child, is under constant discussion, it is unlikely that faulty certification is due to the absence of available knowledge of diseases; on the other hand, certificates are often filled in by junior housemen who have not acquired the art of avoiding terminology that may lead to inquiries by the coroner.The tendency in both of these instances would be towards a more accurate registration if not conventional.We would thus expect the registration in the present survey to be at least as accurate as is likely to occur in the general field of child deaths.Summary A survey of the accuracy of the causes of death given to the registrar at a children's hospital showed that almost one-half of the certifications were not correct as judged by the final pathological diagnosis.We are grateful to Dr. G. H.
Liver Pathophysiology: Its Revelance to Human Disease
Authors: Harry B. Greenberg
Journal: JAMA (1971)

Relating high serum levels of fetoglobulin to hepatoma, Australia antigen to serum hepatitis, and lithocholate to alcoholic hepatitis and cirrhosis, Dr. Davidson details recent concepts of the liver's responses to injury and disease. The test for fetoglobulin, he notes, facilitates curative resection of solitary hepatomas. Finding the Australia antigen identifies acute, and perhaps chronic, serum hepatitis. And reducing lithocholate formation and absorption, with antibiotics and cholestyramine, may benefit cirrhotic patients.  Nor does Davidson slight the long-established tests for hepatic injury. He considers the cephalin flocculation and thymol turbidity tests valuable indicators of hepatocellular disease and discusses the autoimmune phenomena distinguishing primary biliary cirrhosis and chronic hepatitis. High concentrations of γ-globulin (where most antibodies reside), frequently positive LE cell tests, and antibodies to tissues including liver, denote altered immune mechanisms. However, he finds that suppressing the immune responses of patients with chronic hepatitis (with adrenal steroids, azathioprine, and mercaptopurine) is temporarily
Mechanism of cholate uptake: NA+-cotransport, but not cholate/OH− exchange
Authors: Sawkat M. Anwer
Journal: Hepatology (1990)

The mechanism(s) and driving force(s) for hepatocellular uptake of the unconjugated bile acid cholate were investigated in isolated basolateral (sinusoidal) rat liver plasma membrane (blLPM) vesicles and in protein free liposomes. In blLPM vesicles both an inwardly directed Na + gradient and a transmembrane pH difference (8.0 in/6.0 out) stimulated cholate uptake 2-3-fold above equilibrium uptake values (overshoot). While Na + gradient driven cholate uptake could be inhibited by the anion transport inhibitor 4,4′-diisothiocyanato-2,2′-disulfonic acid stilbene (DIDS), the pH gradient dependent portion of cholate uptake was insensitive to DIDS, but could be inhibited by furosemide. Furthermore, initial rates (1-s values) of the pH gradient stimulated cholate uptake were linear with increasing substrate concentrations (no saturability). In liposomes a similar inside alkaline pH gradient also induced a transient DIDS insensitive/furosemide inhibitable intravesicular accumulation (approx. 2-fold) of cholate (overshoot). These findings confirm that hepatocellular uptake of cholate occurs in part via the common Na + /bile acid cotransport system. In addition, the data strongly indicate that in isolated membrane vesicles pH gradient driven cholate uptake represents nonionic diffusion rather than a carrier mediated process (Blitzer, B.L., Terzakis, C. and Scott, K.A. (1986) J. Biol. Chem. 261, 12042-12046). Since in the perfused liver DIDS inhibited uptake of both cholate and taurocholate to a similar extent, DIDS-insensitive pH gradient dependent membrane diffusion appears to be of minor significance for cholate uptake in the intact organ.
Threat to the Development of the Teaching Nursing Home
Authors: Leslie S. Libow
Journal: JAMA (1985)

IN 1981,The Journalaccelerated growth of the concept of high-quality care for the elderly by publishing a far-reaching article, "The Teaching Nursing Home."<sup>1</sup>Academic nursing home programs existed in the early 1970s, but they were few. The goals of these pioneer programs were to develop an improved quality of care in nursing homes and a geriatric health care system that would enhance the quality of patient care, produce the first US geriatricians, and broaden and improve the training of physicians.<sup>2,3</sup> In the ensuing years, through the impetus of demographic change, creative projects launched by the National Institute on Aging and the Robert Wood Johnson Foundation, and the federal government's Medicare and Medicaid programs, more teaching nursing homes have emerged. With the cooperation of affiliated acute-care hospitals and community service networks, these academic nursing homes have made promising progress toward their goals<sup>4</sup>and serve as models for
Multicentric Castleman's disease with an increased serum level of macrophage colony-stimulating factor
Authors: Muneyasu Lee, Makoto Hirokawa, Satoru Matuoka, Hitoshi Hasegawa, Hiroshi Nanjo, Takashi Matsushima, Hideo Imatani, Akira B. Miura
Journal: American Journal of Hematology (1997)

We describe a 74-year-old patient with multicentric Castleman's disease (MCD) whose serum macrophage colony-stimulating factor level was elevated. Serum levels of tumor necrosis factor-α and interleukin 6 were also elevated at presentation, and they returned to normal levels after chemotherapy. Although the total serum cholesterol level was below normal on admission, it increased after chemotherapy. These results suggest that the activation of monocytes or macrophages may be involved in certain pathological phenomena in MCD. Am. J. Hematol. 54: 321–323, 1997. © 1997 Wiley-Liss, Inc.
THE NATURE OF PROSTATIC HYPERTROPHY. ROBERT HOLMES GREENE, A.M., M.D.
Authors: HARLOW BROOKS
Journal: JAMA (1902)

In the introduction of this paper the writers wish to state that there is no expectation on their part that they will be able to settle definitely at once all the questions concerning the nature of prostatic hypertrophy. Their object is to place on record a somewhat exhaustive report of the histologic examination, of a considerable number of prostates, to mention the results of some clinical experience and to present the conclusions to which the data have directed them. An exhaustive consideration of the theories and data of other observers must, on account of lack of space, be omitted. By confining ourselves to a consideration of the conclusions of observations made during the past five years by those who have had a large amount of material at their command and eliminating those whose conclusions have been made from theoretical considerations, the field to be looked over can be made narrow.
Single dose vitamin D treatment for osteomalacia in the elderly.
Authors: J Burns, C R Paterson
Journal: BMJ (1985)

Cervical intraepithelial neoplasia in postmenopausal women with negative cervical cytology Four cases of cervical intraepithelial neoplasia were detected among 50 postmenopausal women in whom cytological examination of a cervical smear yielded negative results, indicating the need for cytological surveillance of women into old age. Patients, methods, and resultsCytological and colposcopic examination of the cervix was performed in 50 women presenting to a menopausal clinic with symptoms of the climacteric before they began hormone replacement treatment.The mean (SD) age 1 Husain DAN. Britain's failure to prevent deaths from cervical cancer.Br.
Bacterial toxins affect early events of T lymphocyte activation.
Authors: S J Stewart, V Prpic, J A Johns, F S Powers, S E Graber, J T Forbes, J H Exton
Journal: Journal of Clinical Investigation (1989)

The effects of pertussis toxin and cholera toxin on early events of T lymphocyte activation were examined in the T lymphocyte cell line, Jurkat. Pertussis toxin treatment of these T cells increased inositol phosphates production and led to increases in intracellular free calcium concentration. These effects were produced by the isolated B (binding) subunit of pertussis toxin, alone. Inositol phosphates production resulting from perturbation of the T cell antigen receptor-CD3 complex by MAb was not affected by pertussis toxin treatment but was markedly inhibited by cholera toxin. This effect of cholera toxin paralleled elevations in cAMP content. However, forskolin, in concentrations equipotent for cAMP production, was a weaker inhibitor of inositol phosphates production. Cholera toxin inhibition of inositol phosphates production did not result from inhibition of baseline incorporation of inositol into phosphoinositide substrates of phospholipase C. These studies underline the complexity of toxin effects on cellular systems and suggest that other approaches will be required to implicate guanine nucleotide-binding regulatory proteins in control of the early events of T lymphocyte activation. However, the data presented here provide a molecular basis for the clinical observations of lymphocytosis and the in vitro observations of lymphocyte mitogenesis after pertussis toxin stimulation.
Ventricular fibrillation thresholds in Langendorff perfused rabbit hearts: all or none effect of low potassium concentration
Authors: M. MacCONAILL
Journal: Cardiovascular Research (1987)

The median single pulse ventricular fibrillation threshold of 56 determinations in eight isolated rabbit hearts perfused with a Krebs-Henseleit solution was 36 mA, with a range from 12.5 to above 50 mA. The fibrillation threshold remained in the same range when the potassium concentration in the perfusing fluid was decreased from its normal 5.6 mmol.litre-1 to as low as 1.8 mmol.litre-1. A further decrease in potassium concentration reduced the fibrillation threshold to a median value of 1.6 mA in nine determinations on six hearts. With a 1.6 mmol.litre-1 potassium concentration, thresholds were in either the high or the low range depending on the individual heart. A pronounced shortening of refractory period and an earlier vulnerable period were associated with the sharp change in fibrillation threshold; the diastolic extrasystolic threshold, cycle length, and RT interval duration increased in a more linear manner as the potassium concentration was lowered.
SEQUELAE OF EPIDEMIC (LETHARGIC) ENCEPHALITIS
Authors: WILLIAM HOUSE
Journal: JAMA (1922)

Recent literature on epidemic encephalitis has been so extensive that any addition may be a bore. Nevertheless, such a probability is here risked in the hope of presenting a reasonably simple working classification of the sequelae of that disease. H. G. Wells, writing of the education of the middle part of the last century, recently said, "The test of a good style was its abundance of quotations, allusions and stereoptyped expressions." With all deference to the extensively reviewed writing and opinions of others, the practice that Wells scorns will be avoided on the ground that the literature is readily available and that time limits will permit of few excerpts. These remarks are based on an examination of 145 patients with epidemic encephalitis, ninety of whom were examined during acute and fifty-five during chronic stages of the disease or because of sequelae. Many of the patients were examined at remote distances
Low plasma coenzyme Q10 levels as an independent prognostic factor for melanoma progression
Authors: Luigi Rusciani, Ilaria Proietti, Antonio Rusciani, Andrea Paradisi, Gregoriana Sbordoni, Carmine Alfano, Simona Panunzi, Andrea De Gaetano, Silvio Lippa
Journal: Journal of the American Academy of Dermatology (2005)
Intrinsic differences in various segments of the proximal convoluted tubule.
Authors: H R Jacobson, J P Kokko
Journal: Journal of Clinical Investigation (1976)

Until recently it has not been possible to compare directly the function of superficial and juxtamedullary nephrons. The present studies, using in vitro microperfusion, were designed to examine whether functional differences exist between proximal convoluted tubule segments of superficial and juxtamedullary nephrons. Electrophysiological studies showed that major differences exist between the relative chloride and sodium permeabilities of these segments. In the 1st mm of the superficial proximal convoluted tubule, the permeability to sodium was greater than that to chloride, whereas in the 2nd mm of the superficial proximal convoluted tubule and all later segments, the permeability to chloride was greater than that to sodium. The juxtamedullary proximal convoluted tubule was found to differ from the superficial proximal convoluted tubule in two respects: first, the relative permeabilities to chloride and sodium did not differ in the various segments of the juxtamedullary proximal convoluted tubule; second, the permeability to sodium was greater than to chloride throughout. When perfused with a solution lacking glucose and amino acids, the superficial and juxtamedullary convolutions exhibited the same transepithelial potential change, a reversible decrease to less than -- 1 mV. It thus appears that in both convolutions there exists electrogenic sodium transport coupled to the transport of these organic solutes. This differs from pars recta of both of these nephrons, which have been shown to exhibit electrogenic sodium transport independent of organic solutes. However, when perfused with a solution lacking glucose and amino acids but also containing high chloride and low bicarbonate concentrations, the superficial convolution developed a significantly more positive potential than the juxtamedullary. This difference reflects greater relative chloride permeability in the superficial proximal convolution. These studies show that intrinsic functional differences exist between proximal convoluted tubules obtained from the superficial and juxtamedullary nephron populations.
Abstract 4067: Pegylated arginine deiminase (ADI-PEG20) as a potential novel therapy for argininosuccinate synthetase-deficient acute myeloid leukemia
Authors: Peter W. Szlosarek, Fiona Luong, Andrew Clear, David Taussig, Simon Joel, Maria Calaminici, Silvana Debernardi, Jude Fitzgibbon, John S. Bomalaski, Arthur E. Frankel, Dominique Bonnet
Journal: Cancer Research (2011)

Abstract Acute myeloid leukemia (AML) is the most common leukemia in adults and the second most common leukemia in children, accounting for a significant share of health care costs with ten thousand cases diagnosed per annum in the US alone. Enzyme-based therapy in the form of asparaginase has revolutionized the treatment of acute lymphoblastic leukemia and there is increasing interest in exploiting analogous tractable metabolic defects in AML. Interestingly, arginine auxotrophic tumors due to deficiency of the rate-limiting enzyme for arginine production, argininosuccinate synthetase (ASS1) are susceptible to arginine-degrading enzymes. Here, we studied whether ASS1 negativity would predict for the efficacy of pegylated arginine deiminase (ADI-PEG20) using AML cell lines and primary AML samples. A lack of ASS1 protein was identified in three of seven leukemic cell lines (K562, Kasumi and KG-1) and in all nine samples from patients with cytogenetically normal and abnormal karotype AML. Methylation of the ASS1 promoter correlated with reduced levels of ASS1 mRNA and absence of ASS1 expression. Bone marrow trephines from patients with AML revealed absence of ASS1 protein in 87% (46/53) of samples by immunohistochemistry, indicating that ASS1 expression may be a biomarker of response to ADI-PEG20 in vivo. Increased levels of ASS1 mRNA and detectable ASS1 protein expression were noted in acute promyelocytic leukemia with the translocation t(15;17). Significantly, ADI-PEG20 reduced the viability of ASS1-negative AML lines whereas the ASS1-positive control lines, Fujioka and U937, were resistant to drug-induced arginine deprivation. Recently, we have identified primary ASS1-negative AML samples with good engraftment in NOD/SCID mice and are proceeding to test the efficacy of ADI-PEG20 using this primary AML xenograft model. Based on our preliminary data and the potential efficacy with low toxicity of arginine deprivation in humans, a phase II trial of ADI-PEG20 is planned in patients with relapsed AML. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4067. doi:10.1158/1538-7445.AM2011-4067
Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk
Authors: Ben Zhang, Wei-Hua Jia, Koichi Matsuda, Sun-Seog Kweon, Keitaro Matsuo, Yong-Bing Xiang, Aesun Shin, Sun Ha Jee, Dong-Hyun Kim, Qiuyin Cai, Jirong Long, Jiajun Shi, Wanqing Wen, Gong Yang, Yanfeng Zhang, Chun Li, Bingshan Li, Yan Guo, Zefang Ren, Bu-Tian Ji, Zhi-Zhong Pan, Atsushi Takahashi, Min-Ho Shin, Fumihiko Matsuda, Yu-Tang Gao, Jae Hwan Oh, Soriul Kim, Yoon-Ok Ahn, Andrew T Chan, Jenny Chang-Claude, Martha L Slattery, Stephen B Gruber, Fredrick R Schumacher, Stephanie L Stenzel, Graham Casey, Hyeong-Rok Kim, Jin-Young Jeong, Ji Won Park, Hong-Lan Li, Satoyo Hosono, Sang-Hee Cho, Michiaki Kubo, Xiao-Ou Shu, Yi-Xin Zeng, Wei Zheng
Journal: Nature Genetics (2014)
Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver transplant recipients
Authors: Hung-Patrick Pham, Cyrille Féray, Didier Samuel, Michèle Gigou, Daniel Azoulay, Valérie Paradis, Francis Ducret, Bernard Charpentier, Brigitte Debuire, Antoinette Lemoine
Journal: Kidney International (1998)
Abstract 1834: Targeting ABC transporters in cancer through small molecule inhibitors
Authors: Tony Huynh, Amanda Tivnan, Marcia Munoz, Leanna Cheung, Anasuya Vishvanath, Claudia Flemming, Fujiko Watt, Catherine Burkhart, Andrei Gudkov, Jamie Fletcher, Michelle Henderson, Murray Norris, Michelle Haber
Journal: Cancer Research (2012)

Abstract Multidrug resistance is one of the major causes of treatment failure in cancer therapy. While multidrug transporter proteins are known for their contributions to chemoresistance and efflux of anti-cancer drugs from cancer cells, a significant body of evidence points to their fundamental roles in tumour biology (Fletcher et al, Nature Rev Cancer, 10:147-156, 2010). We have investigated the ABCC subfamily of multidrug transporter genes in the highly malignant and aggressive childhood solid tumour, neuroblastoma and found that high levels of ABCC1 and ABCC4 are powerful independent prognostic indicators of clinical outcome. However, the agents used to treat the patients described in these studies are not known substrates of ABCC4 and we have shown that siRNA-mediated knockdown of ABCC4 results in reduced proliferation and enhanced morphological differentiation of neuroblastoma cells, in the absence of any cytotoxic drug treatment (Henderson et al, JNCI, 103;1-16, 2011). The aim of this study is to develop a potential new approach for the treatment of neuroblastoma through the inhibition of ABCC4 using small molecule inhibitors. A cell-based screen of a library of diverse chemical small molecules was used to isolate potent small molecule inhibitors of ABCC4 that were able to sensitize HEK293 cells over-expressing MRP4 to a cytotoxic MRP4 substrate, 6-mercaptopurine (6MP). Filtering of compounds based upon their ability to cause 6MP accumulation, together with focused library screening, have resulted in the identification of several chemical structures able to specifically block MRP4. In addition to reversing drug resistance to 6MP, these compounds cause morphological differentiation and inhibition of cell growth, as seen with MRP4 siRNA, in the BE2C neuroblastoma cell line. Importantly, these compounds significantly potentiate morphological differentiation caused by the established differentiation agent, all-trans retinoic acid. We further show that these inhibitors have potency in other MRP4 expressing cancer cell lines beyond neuroblastoma. These pharmacological inhibitors offer clinical potential for the treatment of neuroblastoma and other MRP4 overexpressing cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1834. doi:1538-7445.AM2012-1834
Does change in blood pressure predict heart disease?
Authors: A Hofman, M Feinleib, R J Garrison, A van Laar
Journal: BMJ (1983)

Whether a change in blood pressure is related to the occurrence of cardiovascular disease, independent of blood pressure level, was investigated using data collected in the Framingham heart study on 5209 subjects. The follow up period of 26 years was divided into a first period of 12 years in which the blood pressure change was computed for each individual and a subsequent period of 14 years in which the risk of cardiovascular disease was determined. Blood pressure change was positively related to risk of cardiovascular disease. This association remained when blood pressure level at the start of the study was taken into account but disappeared when the level attained after the first 12 years was taken into consideration. For the clinician this suggests that the decision to treat high blood pressure is best guided by the actual level of pressure and not by its long term trend in the past.