tbuckley/cabot-search huggingface dataset:
Bile salt and micellar fat concentration in proximal small bowel contents of ileectomy patients
Authors: B. W. Van Deest, J. S. Fordtran, S. G. Morawski, J. D. Wilson
Journal: Journal of Clinical Investigation (1968)

Studies were carried out to test the hypothesis that abnormal bile salt metabolism (interruption of the enterohepatic circulation) is responsible for steatorrhea in patients with ileal disease and (or) ileectomy.Duodenal bile salt concentration after a single, standard meal eaten at 8 a.m. was measured in 8 patients with ileectomy steatorrhea and compared with 11 normal control subjects and 7 hospitalized patients without gastrointestinal disease. Mean bile salt concentration was approximately half normal in the ileectomy group, but some of the patients fell well within the normal range, even on repeat studies. However, it was shown that the second and third meals eaten during a single day were associated with a marked depression of duodenal bile salt concentration in ileectomy patients, which suggested that the first meals in these patients flush out a large fraction of the bile salt pool. Simultaneously measured turnover studies with taurocholate-(14)C showed at t((1/2)) of 3.1 hr in these patients compared with 29.5 and 32 hr in two control subjects, proving that the enterohepatic circulation had indeed been interrupted by ileectomy. Hepatic synthesis can apparently partially reconstitute the bile salt pool during the overnight period. Additional studies were carried out to determine the relation between bile salt and micellar fat concentration in proximal small bowel contents after ingestion of the same standard meal. Below a bile salt concentration of 1.7 mg/ml, less than 0.8 mg/ml of lipid existed in the micellar phase of intestinal contents, whereas when bile salt concentration exceeded this level the amount of fat in the micellar phase rose progressively. Only 1 of 11 samples from three ileectomy patients had a micellar fat concentration > 0.8 mg/ml, whereas 33 of 42 samples from control subjects had micellar fat concentration > 0.8 mg/ml.Thus, abnormally low duodenal bile salt concentration during at least a portion of the day, with the associated depression of micellar fat, appears to be a major cause of decreased fat absorption in patients with ileectomy steatorrhea.
Serial analysis of imaging parameters in patients with newly diagnosed glioblastoma multiforme
Authors: Y. Li, J. M. Lupo, M.-Y. Polley, J. C. Crane, W. Bian, S. Cha, S. Chang, S. J. Nelson
Journal: Neuro-Oncology (2011)

The objective of this study was to test the predictive value of serial MRI data in relation to clinical outcome for patients with glioblastoma multiforme (GBM). Sixty-four patients with newly diagnosed GBM underwent conventional MRI and diffusion-weighted and perfusion-weighted imaging postsurgery and prior to radiation/chemotherapy (pre-RT), immediately after RT (post-RT), and every 1–2 months thereafter until tumor progression, up to a maximum of 1 year. Tumor volumes and perfusion and diffusion parameters were calculated and subject to time-independent and time-dependent Cox proportional hazards models that were adjusted for age and MR scanner field strength. Larger volumes of the T2 hyperintensity lesion (T2ALL) and nonenhancing lesion (NEL) at pre-RT, as well as increased anatomic volumes at post-RT, were associated with worse overall survival (OS). Higher normalized cerebral blood volumes (nCBVs), normalized peak height (nPH) and normalized recirculation factors (nRF) at pre-RT, and nCBV at post-RT, in the T2ALL and NEL, were associated with shorter progression-free survival (PFS). From pre- to post-RT, there was a reduction in nCBV and nPH and an increase in apparent diffusion coefficient (ADC). Patients with lower nRF values at pre-RT, or a larger increase in nRF from pre-RT to post-RT, had significantly longer PFS. Time-dependent analysis showed that patterns of changes in ADC and anatomic volumes were associated with OS, while changes in nCBV, nPH, and the contrast-enhancing volume were associated with PFS. Our studies suggest that quantitative MRI variables derived from anatomic and physiological MRI provide useful information for predicting outcome in patients with GBM.
Antifibrotic, Antioxidant, and Immunomodulatory Effects of Mesenchymal Stem Cells in HOCl-Induced Systemic Sclerosis
Authors: Alexandre T. J. Maria, Karine Toupet, Claire Bony, Nelly Pirot, Marie‐Catherine Vozenin, Benoît Petit, Pascal Roger, Frédéric Batteux, Alain Le Quellec, Christian Jorgensen, Danièle Noël, Philippe Guilpain
Journal: Arthritis & Rheumatology (2015)

Systemic sclerosis (SSc) is a rare intractable disease with unmet medical need and fibrosis-related mortality. Absence of efficient treatments has prompted the development of novel therapeutic strategies, among which mesenchymal stem cells/stromal cells (MSCs) or progenitor stromal cells appear to be one of the most attractive options. The purpose of this study was to use the murine model of hypochlorite-induced SSc to investigate the systemic effects of MSCs on the main features of the diffuse form of the disease: skin and lung fibrosis, autoimmunity, and oxidative status.We compared the effects of different doses of MSCs (2.5 × 10(5) , 5 × 10(5) , and 10(6) ) infused at different time points. Skin thickness was assessed during the experiment. At the time of euthanasia, biologic parameters were quantified in blood and tissues (by enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, assessment of collagen content). Assessments of histology and immunostaining were also performed.A lower expression of markers of fibrosis (Col1, Col3, Tgfb1, and aSma) was observed in both skin and lung following MSC infusion, which was consistent with histologic improvement and was inversely proportional to the injected dose. Importantly, sera from treated mice exhibited lower levels of anti-Scl-70 autoantibodies and enhanced antioxidant capacity, confirming the systemic effect of MSCs. Of interest, MSC administration was efficient in both the preventive and the curative approach. We further provide evidence that MSCs exerted an antifibrotic role by normalizing extracellular matrix remodeling parameters as well as reducing proinflammatory cytokine levels and increasing antioxidant defenses.The results of this study demonstrate the beneficial and systemic effects of MSC administration in the HOCl murine model of diffuse SSc, which is a promising finding from a clinical perspective.
Evidence for health policy in India: do we have enough data?
Authors: Giridhara R Babu
Journal: Journal of the Royal Society of Medicine (2012)

Recently, two reports were published in leading journals. The first report in Lancet (Vol.379: May12, 2012) by Rajesh Dikshit et al., infers that the most common fatal cancer in women aged 30–69 years is cervical with burden of 17.1%1. The latest paper in the Journal of the Royal Society of Medicine states the highest age-adjusted mortality rate of 7.7 per 100,000 as being for cervical cancer2. Earlier evidence suggests it is around 65.5 in a rural area3. Thus the range of estimates for the disease burden varies from a low of 7.7 to a high of 65.5. For policy makers, this poses as a significant problem, as to which estimate to trust?

All the population-based registries from India and other data sources, as in the recent article, refer to data mostly from cancers reported from registries. Those depend mainly data from urban conurbations of the country2. The data from registries in India cover less than five percent of the total population of the country. Conclusions drawn from these registries cannot be viewed as representative of the total population, given that rural areas are mostly missed out, and cervical cancer rates might be higher in rural areas. The new cases of cancer detected by registries underrepresent the total number of cases, and may overrepresent the less severe cases or cases from upper socioeconomic strata who are able to afford healthcare4.

At best, none of these studies can provide causal interpretations. Methodologically, none of these papers have sufficient information to tackle one putative question: whether cancer of the cervix is highly prevalent or not in India. Hence, authors of the paper did not have reliable data to either support or reject the idea that HPV vaccine should be put to trial5.
A Two-Year Randomized Trial of Obesity Treatment in Primary Care Practice
Authors: Thomas A. Wadden, Sheri Volger, David B. Sarwer, Marion L. Vetter, Adam G. Tsai, Robert I. Berkowitz, Shiriki Kumanyika, Kathryn H. Schmitz, Lisa K. Diewald, Ronald Barg, Jesse Chittams, Reneé H. Moore
Journal: New England Journal of Medicine (2011)

Calls for primary care providers (PCPs) to offer obese patients behavioral weight-loss counseling have not been accompanied by adequate guidance on how such care could be delivered. This randomized trial compared weight loss during a 2-year period in response to three lifestyle interventions, all delivered by PCPs in collaboration with auxiliary health professionals (lifestyle coaches) in their practices.We randomly assigned 390 obese adults in six primary care practices to one of three types of intervention: usual care, consisting of quarterly PCP visits that included education about weight management; brief lifestyle counseling, consisting of quarterly PCP visits combined with brief monthly sessions with lifestyle coaches who instructed participants about behavioral weight control; or enhanced brief lifestyle counseling, which provided the same care as described for the previous intervention but included meal replacements or weight-loss medication (orlistat or sibutramine), chosen by the participants in consultation with the PCPs, to potentially increase weight loss.Of the 390 participants, 86% completed the 2-year trial, at which time, the mean (±SE) weight loss with usual care, brief lifestyle counseling, and enhanced brief lifestyle counseling was 1.7±0.7, 2.9±0.7, and 4.6±0.7 kg, respectively. Initial weight decreased at least 5% in 21.5%, 26.0%, and 34.9% of the participants in the three groups, respectively. Enhanced lifestyle counseling was superior to usual care on both these measures of success (P=0.003 and P=0.02, respectively), with no other significant differences among the groups. The benefits of enhanced lifestyle counseling remained even after participants given sibutramine were excluded from the analyses. There were no significant differences between the intervention groups in the occurrence of serious adverse events.Enhanced weight-loss counseling helps about one third of obese patients achieve long-term, clinically meaningful weight loss. (Funded by the National Heart, Lung, and Blood Institute; POWER-UP ClinicalTrials.gov number, NCT00826774.).
Altered expression of the Smad signalling pathway: implications for COPD pathogenesis
Authors: A. Zandvoort, D. S. Postma, M. R. Jonker, J. A. Noordhoek, J. T. W. M. Vos, Y. M. van der Geld, W. Timens
Journal: European Respiratory Journal (2006)

Pulmonary emphysema, as a feature of chronic obstructive pulmonary disease (COPD), is characterised by destruction of alveolar tissue. The present authors previously demonstrated reduced decorin expression in the peribronchial area of COPD patients, reflecting an altered extracellular matrix (ECM) modulation. Decorin transcription is regulated by the transforming growth factor (TGF)-β–Smad pathway, the key intracellular signal route for initiation of ECM component gene transcription. Whether this pathway is aberrantly expressed in COPD is not known. An immunohistochemical study was performed to compare protein expression of TGF-β<sub>1</sub> and TGF-β receptors, Smad 2, 3, 4 and 7, and decorin in lung tissue of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages II and IV COPD patients and controls. Epithelial expression of the inhibitory Smad 7 was significantly lower in patients with GOLD stages II and IV than in controls, with other Smad protein expressions being similar in the groups. The expression of TGF-β<sub>1</sub> and TGF-β receptor type I was significantly lower in stage II patients. Decorin staining of the adventitia and alveolar walls was significantly reduced in COPD stage IV. In conclusion, the transforming growth factor-β–Smad pathway is aberrantly expressed in chronic obstructive pulmonary disease patients, implying an abnormal tissue repair ultimately resulting in reduced decorin production. The results of the present study contribute to better understanding of the pathogenesis of emphysema and the airway fibrosis observed in chronic obstructive pulmonary disease patients.
Early Signs of Alcoholism
Authors: C. Nelson Davis
Journal: JAMA (1977)

"WHAT IS an alcoholic? I'll tell you: anyone who drinks more than I do." It is almost as difficult to define alcoholism as it is to treat it. Joking aside, it is most difficult to identify the early alcoholic, the person whose drinking is destructive of health, emotion, competence, and his human relationships. If alcoholism is identified early, much destruction can be prevented. Alcoholism is insidious. An alcohol user gradually becomes an alcohol misuser who gradually becomes an alcoholic. The speed of progression varies. There are teenage alcoholics, and there are alcoholics who do not land on the rocks until they are 80 years old. In most cases, however, the alcoholic is in difficulty ten years before he seeks or is forced to seek help because of severe illness. This illness does not develop abruptly. Even early alcohol abuse is destructive. During the prodromal years, the signs and symptoms of
Outcome of liver transplantation in patients with hemochromatosis
Authors: Frank J. Farrell, Marie Nguyen, Susan Woodley, Joanne C. Imperial, Richard Garcia-Kennedy, Kevin Man, Carlos O. Esquivel, Emmet B. Keeffe
Journal: Hepatology (1994)

Recent preliminary reports suggest a poor outcome of orthotopic liver transplantation for patients with hemochromatosis. We analyzed an institutional experience with orthotopic liver transplantation for hemochromatosis, focusing on factors contributing to increased morbidity and mortality. Between March 1988 and October 1992, nine of 249 adults (3.6%) undergoing orthotopic liver transplantation had hemochromatosis. Mean age was 53 yr (range, 42 to 62 yr), and eight of nine patients were men. The diagnosis of hemochromatosis was based on transferrin saturation > 62% and hepatic iron index > 2.0. Only two patients were known to have hemochromatosis before liver transplantation. All nine patients underwent standard cardiac evaluation before transplantation, and no patient had detectable pre-existing cardiac disease. One patient had a major operative cardiac complication as a result of pulmonary embolism and made a full recovery. Postoperatively, congestive heart failure developed in three patients and four patients had arrhythmias. One patient is undergoing phlebotomy for post-transplant cardiac complications from hemochromatosis. Two patients had primary hepatic tumors in the explant liver. There were four deaths caused by multiorgan failure with congestive heart failure (1), infection (2), and/or malignancy (2). Five patients are alive 3 to 25 mo post-transplant. The actuarial survival of the nine patients was 53% at 25 mo vs. 89% for 18 age- and sex-matched control transplant recipients (p = 0.1) and 81% for all other adult liver transplant recipients (p < 0.01). In five of seven patients, post-transplant liver biopsies revealed hepatic iron accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Oral Contraceptive Use and Fibrocystic Breast Disease With Special Reference to Its Histopathology&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: H Pastides, J L Kelsey, V A LiVolsi, T R Holford, D B Fischer, I S Goldenberg
Journal: JNCI Journal of the National Cancer Institute (1983)

The relationship between use of oral contraceptives and fibrocystic breast disease was examined in a hospital-based case-control study undertaken in New Haven, Connecticut, from 1977 to 1979. Particular emphasis was placed on the extent of epithelial atypia and other histopathologic characteristics found in the biopsy specimens from the cases. Women who had ever used oral contraceptives were at a somewhat decreased risk for fibrocystic disease as a whole. Cases with high atypia and controls had similar patterns of oral contraceptive use, whereas cases with low and intermediate atypia had less oral contraceptive use than controls. Cases with intermediate atypia reported the lowest oral contraceptive use. Subjects with biopsy specimens exhibiting gross cysts, microscopic cysts, or papillomatosis were about 50% less likely to have used oral contraceptives than controls.
Electrocardiographic and electrophysiologic characteristics of ventricular tachycardia originating within the pulmonary artery
Authors: Yukio Sekiguchi, Kazutaka Aonuma, Atsushi Takahashi, Yasuteru Yamauchi, Hitoshi Hachiya, Yasuhiro Yokoyama, Yoshito Iesaka, Mitsuaki Isobe
Journal: Journal of the American College of Cardiology (2005)
Interleukin‐21 Receptor Deficiency Increases the Initial Toll‐like Receptor 2 Response but Protects Against Joint Pathology by Reducing Th1 and Th17 Cells During Streptococcal Cell Wall Arthritis
Authors: Renoud J. Marijnissen, Debbie M. Roeleveld, Deborah Young, Cheryl Nickerson‐Nutter, Shahla Abdollahi‐Roodsaz, Sabrina Garcia de Aquino, Fons A. J. van de Loo, Annemiek B. van Spriel, Annemieke M. H. Boots, Wim B. van den Berg, Marije I. Koenders
Journal: Arthritis & Rheumatology (2013)

Objective The cytokine interleukin‐21 (IL‐21) can have both proinflammatory and immunosuppressive effects. The purpose of this study was to investigate the potential dual role of IL‐21 in experimental arthritis in relation to Th17 cells. Methods Antigen‐induced arthritis (AIA) and chronic streptococcal cell wall (SCW) arthritis were induced in IL‐21 receptor–deficient (IL‐21R −/− ) and wild‐type mice. Knee joints, synovial tissue, and serum were analyzed for arthritis pathology and inflammatory markers. Results During AIA and chronic SCW arthritis, IL‐21R deficiency protected against severe inflammation and joint destruction. This was accompanied by suppressed serum IgG1 levels and antigen‐specific T cell responses. Levels of IL‐17 were reduced during AIA, and synovial lymphocytes isolated during SCW arthritis for flow cytometry demonstrated that mainly IL‐17+ interferon‐γ (IFNγ)–positive T cells were reduced in IL‐21R −/− mice. However, during the acute phases of SCW arthritis, significantly higher joint swelling scores were observed, consistent with enhanced tumor necrosis factor and IL‐6 expression. Interestingly, IL‐21R −/− mice were significantly less capable of up‐regulating suppressor of cytokine signaling 1 (SOCS‐1) and SOCS‐3 messenger RNA. IL‐21 stimulation also affected the Toll‐like receptor 2 (TLR‐2)/caspase recruitment domain 15 response to SCW fragments in vitro, indicating that impaired SOCS regulation in the absence of IL‐21 signaling might contribute to the increased local activation during SCW arthritis. Conclusion In contrast to the proinflammatory role of IL‐21 in adaptive immunity, which drives IL‐17+IFN+ cells and joint pathology during chronic experimental arthritis, IL‐21 also has an important immunosuppressive role, presumably by inhibiting TLR signaling via SOCS‐1 and SOCS‐3. If this dual role of IL‐21 in various immune processes is present in human disease, it could make IL‐21 a difficult therapeutic target in rheumatoid arthritis.
The clone size of peripheral CD8 T cells is regulated by TCR promiscuity
Authors: Yi Hao, Nicolas Legrand, Antonio A. Freitas
Journal: The Journal of Experimental Medicine (2006)

Positive selection in the thymus and peripheral T cell survival depend on T cell receptor (TCR)–major histocompatibility complex (MHC) interactions, but it is not yet clear if both events follow exactly the same rules. We studied peripheral T cell survival and clone sizes in conditions of progressive reduction of restricting MHC-bearing cells or progressive ablation of different MHC molecules. Different CD8+ T cell clones/polyclonal populations showed different survival and/or lymphopenia-driven proliferation requirements. We could correlate clone sizes to the capacity of each TCR to interact with different types of MHC complexes. Thus, although repertoire selection in the thymus is mainly conditioned by the affinity of TCR–MHC interactions, peripheral selection is determined by TCR cross-reactivity to environmental ligands.
Protein synthesis in fresh aortic and pulmonary value allografts as an additional test for viability
Authors: N. AL-JANABI, K. GIBSON, J. ROSE, D. N. ROSS
Journal: Cardiovascular Research (1973)

Journal Article Protein synthesis in fresh aortic and pulmonary value allografts as an additional test for viability Get access NAWAL AL-JANABI, NAWAL AL-JANABI From the Homograft Department, National Heart Hospital, London, and the Institute of Cardiology, University of London Search for other works by this author on: Oxford Academic PubMed Google Scholar K. GIBSON, K. GIBSON From the Homograft Department, National Heart Hospital, London, and the Institute of Cardiology, University of London Search for other works by this author on: Oxford Academic PubMed Google Scholar J. ROSE, J. ROSE From the Homograft Department, National Heart Hospital, London, and the Institute of Cardiology, University of London Search for other works by this author on: Oxford Academic PubMed Google Scholar D. N. ROSS D. N. ROSS From the Homograft Department, National Heart Hospital, London, and the Institute of Cardiology, University of London Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 2, March 1973, Pages 247–250, https://doi.org/10.1093/cvr/7.2.247 Published: 01 March 1973
Mn2+-dependent protein phosphatase 1 enhances protein kinase A-induced Ca2+ desensitisation in skinned murine myocardium
Authors: A NEULEN, N BLAUDECK, S ZITTRICH, D METZLER, G PFITZER, R STEHLE
Journal: Cardiovascular Research (2007)

Phosphorylation of proteins in cardiac myofilaments is a major determinant in the regulation of the Ca(2+) sensitivity of contraction. Whereas most reports have focused on effects of phosphorylation, little is known about reverse effects of dephosphorylation in skinned myocardium. Here we studied the effect of the Mn(2+)-dependent catalytic subunit of protein phosphatase 1 (PP1c-alpha) on the Ca(2+) regulation of contraction. In particular, we tested the hypothesis that phosphorylation persists after the skinning procedure and thereby attenuates protein kinase A (PKA)-induced Ca(2+) desensitisation.Effects of Mn(2+) and Mn(2+)-PP1c on the Ca(2+) sensitivity of contraction (pCa(50)) were investigated in triton-skinned cardiac fibres from mice and compared with those of PKA treatment. Phosphorylation of proteins was monitored by autoradiography.PKA treatment significantly decreased the pCa(50) by 0.04 pCa units. In contrast, treatment with PP1c or Mn(2+)-containing PP1c buffer significantly increased the pCa(50) by 0.26 units or 0.09 units, respectively. These Ca(2+) sensitisations were completely reversed by subsequent PKA treatment. Replacement of the endogenous cardiac troponin I (cTnI) in fibres with the phospho-mimicking mutant human cTnI(S22/23D) abolished the PP1c-induced Ca(2+) sensitisation. PP1c removed (32)P which had been incorporated into cTnI and cardiac myosin binding protein C by PKA treatment. PKA incorporated twofold more (32)P into cTnI in fibres pre-treated with PP1c.Mn(2+)-dependent PP1c increases the Ca(2+) sensitivity of contraction of skinned cardiac fibres. This can be ascribed to dephosphorylation of PKA-dependent phosphorylation sites. Hence PKA-dependent phosphorylation of sarcomeric proteins persists to a functionally relevant degree after the skinning procedure.