tbuckley/cabot-search huggingface dataset:
Preapoptotic cell stress response of primary hepatocytes
Authors: Damijan Nipič, Aleš Pirc, Blaž Banič, Dušan Šuput, Irina Milisav
Journal: Hepatology (2010)

Primary hepatocytes are an important in vitro model for studying metabolism in man. Caspase-9 and Bcl-2-associated X protein (Bax) are regulators of the apoptotic pathway. Here we report on the translocation of procaspase-9 and Bax from cytoplasm to nuclei as well as on dispersion of mitochondria; these processes occur after isolation of primary hepatocytes. The observed changes appear similar to those at the beginning of apoptosis; however, the isolated hepatocytes are not apoptotic for the following reasons: (1) cells have a normal morphology and function; (2) the mitochondria are energized; (3) there is no apoptosis unless it is induced by, e.g., staurosporine or nodularin. Staurosporine does not trigger apoptosis through activation of caspase-9, as its activity is detected later than that of caspase-3. We propose that the translocation of procaspase-9 and Bax into the nuclei reduces the ability to trigger apoptosis through the intrinsic apoptotic pathway. The shifts of procaspase-9 and Bax are reversible in the absence of the apoptotic trigger; the spontaneous reversion was confirmed experimentally for procaspase-9, whereas Bax shifted from the nuclei to the cytosol and mitochondria after the initiation of apoptosis. To distinguish this process from apoptosis, we call it preapoptotic cell stress response. It shares some features with apoptosis; however, it is reversible and apoptosis has to be induced in addition to this process. Conclusion : Knowledge on preapoptotic cell stress response is important for assessing the quality of the cells used in cell therapies, in regenerative medicine, and of those used for modeling metabolic processes. Hepatology 2010;51:2140–2151
HETEROGENEITY OF FOREARM METABOLISM WITH SPECIAL REFERENCE TO FREE FATTY ACIDS*
Authors: Marcel A. Baltzan, Reubin Andres, Gordon Cader, Kenneth L. Zierler
Journal: Journal of Clinical Investigation (1962)

The metabolism of the forearm of man has been appraised by application of the Fick prin- ciple (1).The data were interpreted as in- dicative of the metabolism of skeletal muscle, because some two-thirds of the bulk of the forearm is skeletal muscle and because approximately 85 per cent of forearm blood flow perfuses skeletal muscle.These data on 14 subjects showed that resting skeletal muscle of the forearm, with the subject in the basal state, consumed oxygen vigor- ously and that only 7 + 71 per cent of its 02 up- take could be accounted for by oxidation of glu- cose abstracted from arterial blood.Because forearm respiratory quotient was 0.80 ± 0.03 it was concluded that the major substrate for oxygen consumption by forearm muscles was lipid.Ad- ditional subjects have now been studied and a summary of this more extensive experience is as follows: 16 + 5 per cent of 02 uptake can be ac- counted for by glucose oxidation (43 subjects), and forearm R.Q. is 0.76 ± 0.02 (45 subjects).The missing substrate(s) for oxidation can be cal- culated to be substances which on oxidation give an R.Q. of 0.71.It was predicted that the plasma lipid fraction oxidized by muscle would prove to be that fraction of fatty acid transported in intimate association with serum albumin, variously called free fatty acid (FFA), unesterified fatty acids (UFA), or nonesterified fatty acids (NEFA).This fraction
Role of ozone and granular activated carbon in the removal of mutagenic compounds.
Authors: M M Bourbigot, M C Hascoet, Y Levi, F Erb, N Pommery
Journal: Environmental Health Perspectives (1986)

The identification of certain organic compounds in drinking water has led water treatment specialists to be increasingly concerned about the eventual risks of such pollutants to the health of consumers. Our experiments focused on the role of ozone and granular activated carbon in removing mutagenic compounds and precursors that become toxic after chlorination. We found that if a sufficient dose of ozone is applied, its use does not lead to the creation of mutagenic compounds in drinking water and can even eliminate the initial mutagenicity of the water. The formation of new mutagenic compounds seems to be induced by ozonation that is too weak, although these mutagens can be removed by GAC filtration. Ozone used with activated carbon can be one of the best means for eliminating the compounds contributing to the mutagenicity of water. A combined treatment of ozone and activated carbon also decreases the chlorine consumption of the treated water and consequently reduces the formation of chlorinated organic compounds.
Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease.
Authors: G Rizkalla, A Reiner, E Bogoch, A R Poole
Journal: Journal of Clinical Investigation (1992)

Changes in the structure of the proteoglycan aggrecan (PG) of articular cartilage were determined immunochemically by RIA and gel chromatography and related to cartilage degeneration documented histologically by the Mankin grading system. Monoclonal antibodies to glycosaminoglycan epitopes were used. In all cartilages, three chondroitin sulfate (CS)-rich populations of large size were observed in addition to a smaller keratan sulfate (KS)-rich population. In grades 7-13 OA cartilages (phase II), molecules were significantly larger than the equivalent molecules of grades 2-6 (phase I). CS chain lengths remained unchanged. In most OA cartilages, a CS epitope 846 was elevated in content, this being most marked in phase II (mean: fivefold). Loss of uronic acid, KS, and hyaluronic acid were only pronounced in phase II OA because of variations in normal contents. Aggregation of PG was unchanged (50-60%) or reduced in OA cartilages, but molecules bearing epitope 846 exhibited almost complete aggregation in normal cartilages. This study provides evidence for the capacity of OA cartilage to synthesize new aggrecan molecules to replace those damaged and lost by disease-related changes. It also defines two phases of PG change in OA: an early predominantly degenerate phase I followed by a net reparative phase II accompanied by net loss of these molecules.
Abstract 5525: Antitumor effect of Realgar in combination with chemotherapy drugs on human gastric cancer cells
Authors: Lian Zhang, Sungkyoung Kim, Wenping Ding, Leizhen Zheng, Li Zhang, Yingying Tong, Siyu Chen
Journal: Cancer Research (2014)

Abstract Background: Realgar, a Chinese traditional medicine, of which the main component is arsenic sulfide (As4A4), has potentially anti-tumor property in various cancers. We aimed to study the antitumor effect of Realgar in combination with chemotherapy drugs on human gastric cancer cells. Methods: Human gastric cancer AGS cells were treated with Realgar in combination with Oxaliplatin, Irinotecan, Cisplatin, 5-FU and docetaxol with escalating dose level. Antitumor effect was measured by 24,48-hr growth inhibition by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell morphology was observed under microscope. Results: Realgar in combination with chemotherapy drugs exhibited a dose-dependent and time-dependent cytotoxic effect on AGS cells. The combination of Realgar and Irinotecan or Cisplatin showed the most potent synergistic effect. Conclusions: Realgar combined with chemotherapy drugs such as Irinotecan or Cisplatin has potent antitumor effect on human gastric cancer cells. Further mechanistic and animal studies are being performed. Citation Format: Lian Zhang, Sungkyoung Kim, Wenping Ding, Leizhen Zheng, Li Zhang, Yingying Tong, Siyu Chen. Antitumor effect of Realgar in combination with chemotherapy drugs on human gastric cancer cells. [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 5525. doi:10.1158/1538-7445.AM2014-5525
Rheumatology education for general practice.
Authors: S A Hull
Journal: Annals of the Rheumatic Diseases (1991)

Sally A HullThe survey by Billings and Mole in 1977showed that about 10% of general practiceconsultations were for musculoskeletal prob-lems.'Withinthislargenumberofconsultationsabout 30% of presenting problems were withthe lumbar and cervical spine. Osteoarthritisand 'non-articular' rheumatism were the nextmost common category, whereas consultationsfor rheumatoid arthritis were few. The sero-negativearthritides, connectivetissuedisorders,and juvenile chronic arthritis wereshownto beonly rarely encountered in general practice.In addition to these familiar diagnostic cat-egories a number of other musculoskeletalsymptoms are presented to the general prac-titioner. Some of these will be found in de-pressed patients as one of the commonestpresenting symptoms of depression in generalpractice is somatic pain, much of which ismusculoskeletal. Postviral muscle
Treatment of Meningitis Due to Friedländers Bacillus
Authors: A. L. Loomis Bell
Journal: New England Journal of Medicine (1955)

THE Friedländer bacillus (Klebsieila pneumoniae) is a relatively rare invader of the central nervous system, but, when encountered, meningitis due to this organism constitutes a major therapeutic problem. Only 119 cases of the infection have been described in the world literature1 since this organism was first described by Friedländer in 1882, and the majority of these cases have appeared in recent years as isolated case reports relating experience with the newer antibiotic agents. A review of these cases reveals that recovery from the infection, virtually nonexistent before the era of specific therapy, has been attributed to the sulfonamides, streptomycin, chlortetracycline . . .
Diversity and organization of human T cell receptor delta variable gene segments.
Authors: S Hata, M Clabby, P Devlin, H Spits, J E De Vries, M S Krangel
Journal: The Journal of Experimental Medicine (1989)

Previous studies of the human TCR-delta gene identified a single commonly used V delta segment, denoted V delta 1. To better understand the extent of the human TCR-delta V gene repertoire, TCR-delta transcripts and gene rearrangements were examined in a new panel of cloned human TCR-gamma/delta lymphocytes. Through this analysis we identified and determined the structures of two new V delta segments, denoted V delta 2 and V delta 3. These V delta segments are different from previously characterized V alpha segments, supporting the notion that the human V delta and V alpha repertoires are distinct. Examination of V gamma gene segment usage in these cells reveals that the V delta 2 gene segment is used in conjunction with the V gamma 2 gene segment. Blot hybridization indicates that the V delta 2 gene segment lies between V delta 1 and D delta-J delta-C delta, and within 100 kb of the latter. Analysis of genomic clones indicates that the V delta 3 gene segment lies in an inverted orientation, approximately 2 kb 3' of C delta. This implies that rearrangement of V delta 3 to D delta-J delta-C delta occurs by inversion. Together with previous mapping studies, these results indicate that human V delta segments are dispersed, rather than clustered, within the TCR-alpha/delta locus. The analysis of rearrangements in polyclonal thymocyte DNA suggests that there may be a limited number of additional V delta gene segments yet to be characterized.
Role of deficient type III interferon-λ production in asthma exacerbations
Authors: Marco Contoli, Simon D Message, Vasile Laza-Stanca, Michael R Edwards, Peter A B Wark, Nathan W Bartlett, Tatiana Kebadze, Patrick Mallia, Luminita A Stanciu, Hayley L Parker, Louise Slater, Anita Lewis-Antes, Onn M Kon, Stephen T Holgate, Donna E Davies, Sergei V Kotenko, Alberto Papi, Sebastian L Johnston
Journal: Nature Medicine (2006)
Rekindling Student Interest in Generalist Careers
Authors: Mark D. Schwartz, William T. Basco, Michael R. Grey, Joann G. Elmore, Arthur Rubenstein
Journal: Annals of Internal Medicine (2005)

Despite changes in the structure of the U.S. health care system, patients continue to need and seek out generalist physicians. However, the proportion of U.S. graduates of medical schools who choose to enter generalist residency training decreased from 50% in 1998 to less than 40% in the 2004 match. Unless we act now to reverse this trend, we may face a shortage of primary care physicians to care for the complex medical needs of an aging population. This article reviews the history of and trends in career choice and proposes 4 evidence-based recommendations to rekindle student interest in generalist careers: 1) We must improve satisfaction and enthusiasm among generalist physician role models. 2) Schools of medicine should redouble their efforts to produce primary care physicians. 3) We must facilitate the pathway from medical school to generalist residency. 4) The U.S. government should increase funding for primary care research and research training. In the absence of a major overhaul of economic incentives in favor of generalist careers, we will need to work at these multiple levels to restore balance to the generalist physician workforce and align with the desires and expectations of patients for continuing healing relationships with generalist physicians.
Detailed Analysis of Visitors to Cancer-Related Web Sites
Authors: Hiroto Narimatsu, Tomoko Matsumura, Tomohiro Morita, Yukiko Kishi, Koichiro Yuji, Masahiro Kami, Tsunehiko Komatsu, Yuji Tanaka, Tomohiro Sawa, Yoshinori Nakata
Journal: Journal of Clinical Oncology (2008)
Temporal Arteritis Heralded by Facial Nerve Palsy
Authors: Andres Roomet
Journal: JAMA (1974)

TO THE BEST of our knowledge, an association between facial nerve paralysis and temporal arteritis has not been reported previously. One such case in which temporal arteritis was heralded by the sudden onset of facial nerve paralysis is presented. Although we cannot rule out mere coincidence, we believe that the facial nerve impairment in this case represented the initial symptom of temporal arteritis. <h3>Report of a Case</h3> A 77-year-old white woman was admitted to the hospital on Oct 12, 1973, with a chief complaint of bilateral blurring of vision. The patient had been well until 12 weeks before admission when she developed complete motor paralysis on the right side of the face, associated with episodic retroauricular pain. Examination showed no other neurologic abnormalities, though taste and hearing were not tested. A diagnosis of facial nerve paralysis (Bell palsy) was made, and the patient's condition improved considerably over the next two
Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis
Authors: Kaushik Choudhuri, Germana V. Gregorio, Giorgina Mieli-Vergani, Diego Vergani
Journal: Hepatology (1998)

We describe two patients with liver kidney microsomal antibody type 1 (LKM1)–positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin–dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross–reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin–dependent diabetes, and 21–hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme–linked immunosorbent assay (ELISA). The cut–off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21–hydroxylase (21–OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross–reactive. We suggest that a cross–reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.
Cc–Chemokine Receptor 6 and Its Ligand Macrophage Inflammatory Protein 3α Might Be Involved in the Amplification of Local Necroinflammatory Response in the Liver
Authors: Yukihiro Shimizu, Hiroyuki Murata, Yoshiro Kashii, Katsuharu Hirano, Hitoshi Kunitani, Kiyohiro Higuchi, Akiharu Watanabe
Journal: Hepatology (2001)

It is not fully understood how antigen–specific or–nonspecific T cells migrate into the liver in various liver diseases. Macrophage inflammatory protein (MIP)–3α is a chemokine that is expressed mostly in the liver, and the receptor CCR6 is reported to be expressed on memory T cells. In the present study, we focused on the expression of CCR6 on T cells from peripheral blood (PB) and inflamed liver, and analyzed the involvement of MIP–3α and CCR6 in the immunopathogenesis of liver diseases. Intrahepatic T cells showed significantly ( P &lt; .0001) higher percentages of CCR6 + CD4 + T cells compared with PB, which is significantly ( P = .037) correlated with the necroinflammatory response in the liver. Most of intrahepatic CCR6 + CD4 + cells were also positive for CCR5, which is known to express on T–helper 1 cells. MIP–3α was stained in the cells located near piecemeal necrosis, where dendritic cells (DCs) are often observed, and coculture of activated DCs with apoptotic cells induced MIP–3α production from the DCs. These data suggest that MIP–3α is produced by periportal DCs and/or macrophages after necroinflammatory response, leading to the recruitment of activated T cells into the liver. This process could be important to augment the local immune response in the livers of various liver diseases. The finding might be important not only for the understanding of immunopathogenesis of liver diseases but also for the therapeutic strategy to control the local immune response in the liver.
Brain death in Britain as reflected in renal donors.
Authors: B Jennett, C Hessett
Journal: BMJ (1981)

The diagnostic mix of 1228 brain-dead renal donors in Britain was similar to that of 479 cases of brain death recently reported from three neurosurgical units. About half the donors came from non-teaching hospitals without a neurosurgical unit, many of them small and distant from the centre. The different circumstances that preceded brain deaths were examined--namely, diagnosis and whether the fatal ictus of brain damage occurred when the patient was already in hospital--to explain why donors spend varying times on the ventilator. Head injuries accounted for half the donors, and intracranial haemorrhage for almost a third. While many potential donors are not made available, the size of the pool has been overestimated, particularly in regard to head injury. Reduction in organ donation since "Panorama" has been very uneven, with some places increasing their yield; this suggests reluctance of doctors to initiate donation rather than relatives withholding permission.
SKIN MANIFESTATIONS OF GIANT-CELL. ARTERITIS.
Authors: P. D. C. KINMONT, D. I. McCALLUM
Journal: British Journal of Dermatology (1964)

Journal Article SKIN MANIFESTATIONS OF GIANT‐CELL. ARTERITIS. Get access P. D. C. KINMONT, M.D., M.R.C.P., P. D. C. KINMONT, M.D., M.R.C.P. Consultant Dermatologist, Derbyshire Royal infirmary, Derby. Consultant Dermatologist. Nottingham General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar D. I. McCALLUM, M.D., D.P.H., F.R.C.P.E. D. I. McCALLUM, M.D., D.P.H., F.R.C.P.E. Consultant Dermatologist, Derbyshire Royal infirmary, Derby. Consultant Dermatologist. Nottingham General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 7, 1 July 1964, Pages 299–308, https://doi.org/10.1111/j.1365-2133.1964.tb14533.x Published: 01 July 1964
Is Prostate Cancer Screening Analogous to Lung Cancer Screening?
Authors: Patrick C. Walsh
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Is prostate cancer more like breast cancer or lung cancer? For reasons that are hard to fathom, Drs Collins and Barry<sup>1</sup>feel that it is more like lung cancer. They dismiss the parallels between prostate cancer screening and breast cancer screening without comment and then focus on the flawed studies in lung cancer that failed to demonstrate a survival benefit.<sup>2</sup>In doing so, they conveniently ignore 2 major flaws in their own logic. First is tumor biology. Prostate cancer is characterized by a slow, natural progression of the disease,<sup>3</sup>whereas the clinical course of lung cancer is frequently established before it can be seen on x-ray examination. For example, by the time the diagnosis of small cell carcinoma of the lung is established, dissemination to distant organ sites has almost always occurred.<sup>4</sup>In lung cancer studies, small cell cancer has comprised 25% of cases.<sup>2</sup>This
Effect of cigarette smoking on human gastric secretory responses
Authors: H. T. Debas, M. M. Cohen, I. B. Holubitsky, R. C. Harrison
Journal: Gut (1971)

The effect of smoking three cigarettes over a one-hour period on the pentagastrinstimulated submaximal plateau of acid and pepsin secretion was observed in 12 healthy human volunteers comprising men and women and smokers and non-smokers. No significant overall change in secretion was observed. In one subject, however, acid secretion was significantly inhibited (p &lt; 0·01) and in one individual significant late stimulation (p &lt; 0·01) of both acid and pepsin was observed.
Helical computed tomography (CT) is safe as the primary diagnostic test in suspected pulmonary embolism (PE)
Authors: A Sathyapala
Journal: Thorax (2003)

<b>Introduction:</b> Patients with pulmonary hypertension and connective tissue diseases (CTD) are currently classified as either having CTD-associated pulmonary arterial hypertension (PAH) when minimal interstitial lung disease (ILD) is evident, or CTD-ILD when the presence of ILD is more profound. We hypothesised that patients with CTD-ILD and PAH may benefit from receiving pulmonary vasodilator therapy, and that the severity of fibrosis and the radiological subtype of ILD will determine outcomes. <b>Methods:</b> We retrospectively collected data from the PH registry at the Royal Brompton Hospital from a 12 year period (2006-2017). All patients had been diagnosed with PH at right heart catheterisation, had an ILD and had received vasodilator therapy. HRCT thorax at diagnosis was scored for pattern and amount of fibrosis present. Clinical parameters (PASP on echocardiogram, serum BNP, 6WMD, PFTs, WHO functional class and emPHasis10 score) were recorded at baseline, at 3-6 months and at each visit thereafter. <b>Results:</b> One hundred and fourteen patients were identified. Mean age was 60.4 years and they were predominantly female (70%), had severe PH (mPAP 40.9 ±10.2 mmHg) and severe lung disease (FVC 66.1±24.8% predicted, TLCO 25.9±9.9% predicted). Fourteen patients had a UIP pattern of ILD, the remaining 100 had non-UIP pattern. 41/114 (36%) of patients had ≤10% fibrosis on CT. Mean follow-up was 42 months and 60/114 (42%) had died at 36 months. <b>Conclusions:</b> Our cohort is predominantly non-UIP disease but UIP pattern of ILD is associated with more rapid progression and worse outcomes. We will report on whether the use of pulmonary vasodilator therapies arrests the decline of lung function and progression of PH in any of the CTD-ILD subtypes.