tbuckley/cabot-search huggingface dataset:
Nonenzymatic glycosylation of erythrocyte membrane proteins. Relevance to diabetes.
Authors: J A Miller, E Gravallese, H F Bunn
Journal: Journal of Clinical Investigation (1980)

Nonenzymatic glycosylation of proteins of the erythrocyte membrane was determined by incubating erythrocyte ghosts with [3H]borohydride. The incorporation of tritium into protein provides a reliable assay of ketoamine linkages. The membrane proteins from 18 patients with diabetes incorporated twice as much radioactivity as membrane proteins from normal erythrocytes. After acid hydrolysis, amino acid analysis showed that the majority of radioactivity was localized to glucosyllysine. Autoradiograms showed that all of the major proteins of the erythrocyte membrane, separated by electrophoresis on sodium dodecyl sulfate gels, contained ketoamine linkages. No protein bands in either normal or diabetic erythrocytes showed significant preferential labeling. Erythrocyte membranes from three patients with hemolytic anemia showed reduced incorporation of tritium from [3H]-borohydride, indicating decreased nonenzymatic glycosylation. Two patients with diabetes and hemolytic anemia had incorporation of radioactivity similar to that of normal individuals. In these groups of patients the incorporation of tritium into erythrocyte membrane proteins correlated with levels of hemoglobin AIc. Thus the modification of membrane proteins like that of hemoglobin depends on blood glucose levels as well as erythrocyte age. These studies show that the enhanced nonenzymatic glycosylation of proteins in diabetics extends beyond hemoglobin to the proteins of the erythrocyte membrane and probably affects other proteins that have slow turnover and are exposed to high concentrations of glucose.
Route dependent effects of 2-chloroadenosine and theophylline in isolated perfused guinea pig hearts
Authors: H W Wei, G S Friedrichs, G F Merrill
Journal: Cardiovascular Research (1991)

Study objective — The adenosine hypothesis for the metabolic regulation of coronary blood flow remains controversial, in part because of differences in results obtained between intravascular and endogenously released adenosine. The main objective of this study was to compare the responses of coronary perfusate flow to intravascular and pericardial 2-chloroadenosine and theophylline. The pericardial route was used to simulate physiological conditions. Design — An isolated, perfused guinea pig heart preparation was used. Hearts were submerged in 10 ml Krebs-Ringer bicarbonate solution having the same chemical compostion as that used to perfuse the coronary vasculature. The submersion fluid was assumed to simulate myocardial interstitial fluid. Hearts were divided into four experimental groups. The first group (n = 6) was used to check that the submerged hearts functioned normally. The second group (n = 12) was used to compare differences between intravascular and pericardial 2-chloroadenosine. The third group (n = 16) was used to evaluate the two routes of administration of 2-chloroadenosine on transmural distribution of coronary flow. The fourth group (n = 24) was used to test the effects of hypoxia in the absence and presence of pericardial theophylline. Experimental material — Hearts were obtained from adult guinea pigs of either sex weighing 300-400 g. Measurements and main results — All submerged hearts were functionally stable for at least 30 min. Pericardial 2-chloroadenosine was about 1000 times less potent than intravascular 2-chloroadenosine in relaxing the coronary vasculature. Venous concentrations of pericardial 2-chloroadenosine were significantly greater than those of intravascular 2-chloroadenosine, at 0.72(SEM 0.17) ν 0.18(0.02) μmol·litre−1. Pericardial 2-chloroadenosine caused more uniform distribution of radiotracer microspheres than intravascular 2-chloroadenosine. Finally, pericardial theophylline significantly attenuated the vasodilator response to hypoxia but not to exogenous adenosine. Conclusion — The isolated submerged heart is a viable preparation for investigating the adenosine hypothesis. Our results suggest that intravascular adenosine does not simulate physiological conditions of interstitial adenosine release and action.
A STUDY OF MALNUTRITION IN CHRONIC SCHIZOPHRENIA
Authors: CRAWFORD N. BAGANZ, JAMES M. NORRIS
Journal: American Journal of Psychiatry (1943)

1. On admission, the degree of malnutrition found in chronic schizophrenic patients is not significantly different from that found in the entire hospital population. 2. While the entire hospital population has little change in the extent of malnutrition following admission there is a significant increase in the extent of malnutrition in chronic schizophrenic patients after these patients had been hospitalized eight years. 3. The proportion of patients ten or more pounds underweight is approximately 50 per cent greater in the chronic schizophrenics studied than it is in the entire hospital population and the same proportion is found to be true in the number of those schizophrenics twenty or more pounds underweight. 4. It would appear that the more active patients have the lowest extent and degree of malnutrition and as the patients become less active the extent and degree of malnutrition becomes more marked. 5. There appears to be no significant correlation between the degree of malnutrition and the type of hospital service rendered to the patient. 6. The extent and degree of malnutrition apparently exists completely independent of the serving of adequate calories. 7. The degree of malnutrition in chronic schizophrenics may offer an explanation for some of the commonly noted changes in the cardiac shadow frequently described as the "longitudinal heart of the præcox."
Prostanoid induces premetastatic niche in regional lymph nodes
Authors: Fumihiro Ogawa, Hideki Amano, Koji Eshima, Yoshiya Ito, Yoshio Matsui, Kanako Hosono, Hidero Kitasato, Akira Iyoda, Kazuya Iwabuchi, Yuji Kumagai, Yukitoshi Satoh, Shuh Narumiya, Masataka Majima
Journal: Journal of Clinical Investigation (2014)

The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We investigated the contribution of COX-2–derived prostaglandin E2 (PGE2) in the formation of a premetastatic niche and LNM. A murine model of Lewis lung carcinoma (LLC) cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node subcapsular regions, and COX-2 inhibition markedly suppressed mediastinal LNM. Stromal cell–derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, an SDF-1 antagonist, and a CXCR4 neutralizing antibody all reduced LNM. Moreover, LNM was reduced in mice lacking the PGE2 receptor EP3, and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. Compared with WT CD11c+ DCs, injection of EP3-deficient CD11c+ DCs dramatically reduced accumulation of SDF-1+CD11c+ DCs in regional LNs and LNM in LLC-injected mice. Accumulation of Tregs and lymph node lymphangiogenesis, which may influence the fate of metastasized tumor cells, was also COX-2/EP3–dependent. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3–dependent induction of SDF-1 and suggest that inhibition of this signaling axis may be an effective strategy to suppress premetastatic niche formation and LNM.
Significance of the Sinus-Node Recovery Time
Authors: ONKAR S. NARULA, PHILIP SAMET, ROGER P. JAVIER
Journal: Circulation (1972)

The phenomenon of postpacing depression of cardiac pacemakers was utilized to evaluate the sinus-node function in 56 patients by analyzing the sinus-node recovery time (SRT), that is, the interval between the last paced P wave and the following sinus P wave. Corrected SRT (CSRT) is defined as the recovery interval in excess of the sinus cycle (SRT — sinus cycle length). The SRT was measured following sinus-node suppression by (1) isolated premature beats (PABs) and (2) atrial pacing (AP) at rates of 100 to 140/min for periods of 2 to 5 min at each level. Twenty-eight patients had normal heart rates (group A), and 28 patients had sinus bradycardia (SB; group B). Ten of the 28 patients with SB were restudied after receiving atropine (2 mg intravenously). The CSRT with PABs was similar in both group A and group B patients and remained essentially unchanged after atropine despite a decrease in sinus cycle length. The phenomenon of interpolated PABs was demonstrated in seven of the 56 patients. In 27 of the 28 patients with normal heart rates (group A), the CSRT with AP ranged from 110 to 525 msec and was essentially independent of the rate and duration of AP. In the remaining one patient of group A, despite a normal heart rate, the CSRT was prolonged (1810 msec) and directly dependent on the rate and duration of AP. In 12 of the 28 patients with SB, the CSRT was comparable to that in group A (≦525 msec). In the remaining 16 patients with SB (group B), the CSRT ranged from 560 to 3740 msec and was usually directly proportional to the rate and duration of AP. After atropine in most of the patients with a prolonged CSRT, the CSRT remained abnormal whereas in others junctional escape beats appeared first, followed eventually by normal sinus rhythm. In a single patient with SB and an abnormal CSRT, restudy 7½ months later again showed a prolonged CSRT indicating the reproducibility of the measurement. The CSRT with AP provides a potentially useful clinical means of assessing the sinus-node function and thereby aids in the diagnosis of the "sick sinus syndrome." It is stressed that AP was found to be more reliable than PABs in eliciting an abnormal response. Furthermore, a normal sinus (atrial) rate does not necessarily provide assurance of a normal sinus-node response to AP, that is, normal sinus-node function.
Comparative strategies to induce long-term graft acceptance in fully allogeneic renal versus cardiac allograft models by CD28-B7 T cell costimulatory blockade
Authors: M Schaub, T H Stadlbauer, A Chandraker, J P Vella, L A Turka, M H Sayegh
Journal: Journal of the American Society of Nephrology (1998)

Blocking CD28-B7 T cell costimulatory activation by the fusion protein CTLA4Ig prevents rejection and induces long-term graft acceptance in various experimental transplant models. There are reported differences in the efficacy of CTLA4Ig in renal and cardiac rodent allograft models, but it is not clear whether these are due to the strain or species differences investigated in the different studies reported. This study investigates the effect of blocking CD28-B7 T cell costimulation with murine CTLA4Ig in rat models of acute renal and cardiac allograft rejection models, using the same complete major histocompatibility complex-incompatible strain combination. A single injection of murine CTLA4Ig 2 d after engraftment was able to induce long-term graft acceptance (> 100 d) in 54% of Lewis rat recipients of Wistar-Furth kidneys. Transferring this protocol into the acute Wistar-Furth to Lewis heart allograft model resulted in a mean graft survival time of 24.7+/-16.9 d, and all grafts were ultimately rejected. Only concomitant injection of donor cells (4 x 10(7) splenocytes) plus a single injection of CTLA4Ig on the day of transplant could induce long-term graft acceptance in 50% of animals. In both the cardiac and renal transplant models, the thymus and spleen were required for induction of tolerance. The maintenance phase of tolerance, however, did not require an intact thymus but did require the presence of a spleen. These data have important clinical applicability because human studies with T cell costimulatory blockade are being planned.
Meta-Analysis of Acute Lung Injury and Acute Respiratory Distress Syndrome Trials Testing Low Tidal Volumes
Authors: Peter Q. Eichacker, Eric P. Gerstenberger, Steven M. Banks, Xizhong Cui, Charles Natanson
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The use of low tidal volumes (5-7 ml/kg measured body weight) as a protective lung strategy is becoming widely recommended for patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (1-4). However, clinical trials testing low tidal volumes in ALI and ARDS have not shown uniform results (5-7). This has led some experts to recommend avoiding high tidal volumes during mechanical ventilation in these patients (6, 8), whereas other experts advocate using very low tidal volumes (1-4). Our concern, shared by others (9), was that trials showing low tidal volumes to be beneficial did not use control arms that reflected the current best practice standards at the time. Instead, the trials compared very low tidal volumes (5-7 ml/kg measured body weight) with traditional tidal volumes (10 ml/kg or more), which were higher than those routinely used (8-9 ml/kg) (10-13). As a result, those studies were inconclusive. We performed a meta-analysis to investigate why five randomized, prospective clinical trials produced disparate results and to critically evaluate the basis for recommending low tidal volume ventilation in ALI and ARDS (3-7). In this analysis, we demonstrate that there is a significant difference in the effects of low tidal volume on survival among the five trials. We then compare the tidal volumes and plateau airway pressures from the five trials to determine whether these account for differences in survival. In contrast to previous explanations based on the low tidal volumes tested (4), this meta-analysis demonstrates that significant differences in the control arms can account for the discrepant results among these five trials.
Systematic Review: The Value of the Periodic Health Evaluation
Authors: L. Ebony Boulware, Spyridon Marinopoulos, Karran A. Phillips, Constance W. Hwang, Kenric Maynor, Dan Merenstein, Renee F. Wilson, George J. Barnes, Eric B. Bass, Neil R. Powe, Gail L. Daumit
Journal: Annals of Internal Medicine (2007)

Background: The periodic health evaluation (PHE) has been a fundamental part of medical practice for decades despite a lack of consensus on its value. Purpose: To synthesize the evidence on benefits and harms of the PHE. Data Sources: Electronic searches of such databases as MEDLINE and the Cochrane Library, review of reference lists, and hand- searching of journals through September 2006. Study Selection: Studies (English-language only) assessing the delivery of preventive services, clinical outcomes, and costs among patients receiving the PHE versus those receiving usual care. Data Extraction: Study design and settings, descriptions of the PHE, and clinical outcomes associated with the PHE. Data Synthesis: The best available evidence assessing benefits or harms of the PHE consisted of 21 studies published from 1973 to 2004. The PHE had a consistently beneficial association with patient receipt of gynecologic examinations and Papanicolaou smears, cholesterol screening, and fecal occult blood testing. The PHE also had a beneficial effect on patient "worry" in 1 randomized, controlled trial but had mixed effects on other clinical outcomes and costs. Limitations: Descriptions of the PHE and outcomes were heterogeneous. Some trials were performed before U.S. Preventive Services Task Force guidelines were disseminated, limiting their applicability to modern practice. Conclusions: Evidence suggests that the PHE improves delivery of some recommended preventive services and may lessen patient worry. Although additional research is needed to clarify the long-term benefits, harms, and costs of receiving the PHE, evidence of benefits in this study justifies implementation of the PHE in clinical practice.
Gene Expression Profiling of Differentiated Thyroid Neoplasms
Authors: Sylvie Chevillard, Nicolas Ugolin, Philippe Vielh, Katherine Ory, Céline Levalois, Danielle Elliott, Gary L. Clayman, Adel K. El-Naggar
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this research was to identify novel genes that can be targeted as diagnostic and clinical markers of differentiated thyroid tumors. Experimental Design: Gene expression analysis using microarray platform was performed on 6 pathologically normal thyroid samples and 12 primary follicular and papillary thyroid neoplasms. Microarrays containing probes for 5,760 human full-length cDNAs were used for hybridization with total RNA from normal and tumor thyroid samples labeled with Cy3-dUTP and Cy5-dUTP, respectively. Scanned array images were recorded, and data analysis was performed. Selected sets of differentially expressed genes were analyzed using quantitative real-time reverse transcription-PCR for verification. Results: We identified 155 genes that differentiate histologically normal thyroid tissues from benign and malignant thyroid neoplasms. Of these 75 genes were differentiated between follicular neoplasms (adenoma and carcinoma) and the follicular variant of papillary carcinoma. Purely follicular neoplasms (adenomas and carcinomas) shared many genetic profiles, and only 43 genes were distinctly different between these tumors. Hierarchical cluster analysis also differentiated conventional papillary carcinoma from its follicular variant and follicular tumors. The differentially expressed genes were composed of members of cell differentiation, adhesion, immune response, and proliferation associated pathways. Quantitative real-time reverse transcription-PCR analysis of selected genes corroborated the microarray expression results. Conclusions: Our study show the following: (1) differences in gene expression between tumor and nontumor bearing normal thyroid tissue can be identified, (2) a set of genes differentiate follicular neoplasm from follicular variant of papillary carcinoma, (3) follicular adenoma and carcinoma share many of the differentiated genes, and (4) gene expression differences identify conventional papillary carcinoma from the follicular variant.
Small intestinal permeability to mannitol and lactulose in the three ethnic groups resident in west Birmingham.
Authors: T H Iqbal, K O Lewis, J C Gearty, B T Cooper
Journal: Gut (1996)

Asymptomatic residents of tropical countries have differences in small intestinal morphology and permeability compared with residents of temperate zones. The aim of this study was to investigate small intestinal permeability and morphology in three ethnic groups resident in Birmingham, UK.28 white patients, 101 Indian (Indian subcontinent), and 49 Afro-Caribbean adult patients with dyspepsia had endoscopic distal duodenal biopsies and a hyperosmolar lactulose/mannitol permeability test. Twenty normal white subjects had the permeability test.Lactulose/mannitol excretion ratios (LMER) were: white subjects 0.022 (median), white patients 0.022, Indians 0.031, Afro-Caribbeans 0.033. Differences between the immigrant groups and the two white groups were significant (p < 0.001); 33% of Indians and 45% of Afro-Caribbeans had LMER outside the range of the white groups. Afro-Caribbeans born in the UK had significantly lower LMER than those born abroad (p < 0.05); a similar trend was seen in Indians. Villous height/mucosal thickness ratios, calculated from small intestinal biopsy specimens, were lower in the immigrant groups and correlated inversely with LMER (r = 0.28; p < 0.05). Time resident in the tropics also correlated inversely with LMER.There were significant differences in small intestinal permeability and morphology between immigrants resident in a Western country and the native white population. The data suggested that these differences were related to environmental factors.
C-Care: Patient Characteristics Associated with Allerject TM Versus EpipenTM Auto-Injector Prescription Across Three Montreal Hospitals
Authors: Bhairavi Balram, Ann Clarke, Sebastian La Vieille, Reza Alizadehfar, Alizee Dery, Christopher Mill, Harley Eisman, Judy Morris, Jocelyn Gravel, Anne Des Roches, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2015)
Relation of Operator Volume and Experience to Procedural Outcome of Percutaneous Coronary Revascularization at Hospitals With High Interventional Volumes
Authors: Stephen G. Ellis, William Weintraub, David Holmes, Richard Shaw, Peter C. Block, Spencer B. King
Journal: Circulation (1997)

Background Although an inverse relation between physician caseload and complications has been conclusively demonstrated for several surgical procedures, such data are lacking for percutaneous coronary intervention, and the ACC/AHA guidelines requiring ≥75 cases per year for operator “competency” are considered by some physicians to be arbitrary. Methods and Results From quality-controlled databases at five high-volume centers, models predictive of death and the composite outcome of death, Q-wave infarction, or emergency bypass surgery were developed from 12 985 consecutively treated patients during 1993 through 1994. Models had moderate to high discriminative capacity (area under ROC curves, 0.65 to 0.85), were well calibrated, and were not overfitted by standard tests. These models were used for risk adjustment, and the relations between both yearly caseload and years of interventional experience and the two adverse outcome measures were explored for all 38 physicians with ≥30 cases per year. The average physician performed a mean±SD of 163±24 cases per year and had been practicing angioplasty for 8±5 years. Risk-adjusted measures of both death and the composite adverse outcome were inversely related to the number of cases each operator performed annually but bore no relation to total years of experience. Both adverse outcomes were more closely related to the logarithm of caseload (for death, r =.37, P =.01; for death, Q-wave infarction, or bypass surgery, r =.58, P &lt;.001) than to linear caseload. Conclusions In this analysis, high-volume operators had a lower incidence of major complications than did lower-volume operators, but the difference was not consistent for all operators. If these data are validated, their implications for hospital, physician, and payer policy will require exploration.
Proteasome Inhibition Causes Regression of Leukemia and Abrogates BCR-ABL–Induced Evasion of Apoptosis in Part through Regulation of Forkhead Tumor Suppressors
Authors: Zainab Jagani, Keli Song, Jeffery L. Kutok, M. Rajan Dewar, Armelle Melet, Tanya Santos, Alexandra Grassian, Saghi Ghaffari, Catherine Wu, Ruibao Ren, Heather Yeckes Rodin, Kenneth Miller, Roya Khosravi-Far
Journal: Cancer Research (2009)

Abstract BCR-ABL plays an essential role in the pathogenesis of chronic myeloid leukemia (CML) and some cases of acute lymphocytic leukemia (ALL). Although ABL kinase inhibitors have shown great promise in the treatment of CML, the persistence of residual disease and the occurrence of resistance have prompted investigations into the molecular effectors of BCR-ABL. Here, we show that BCR-ABL stimulates the proteasome-dependent degradation of members of the forkhead family of tumor suppressors in vitro, in an in vivo animal model, and in samples from patients with BCR-ABL–positive CML or ALL. As several downstream mediators of BCR-ABL are regulated by the proteasome degradation pathway, we also show that inhibition of this pathway, using bortezomib, causes regression of CML-like disease. Bortezomib treatment led to inhibition of BCR-ABL–induced suppression of FoxO proteins and their proapoptotic targets, tumor necrosis factor–related apoptosis-inducing ligand and BIM, thereby providing novel insights into the molecular effects of proteasome inhibitor therapy. We additionally show sensitivity of imatinib-resistant BCR-ABL T315I cells to bortezomib. Our data delineate the involvement of FoxO proteins in BCR-ABL–induced evasion of apoptosis and provide evidence that bortezomib is a candidate therapeutic in the treatment of BCR-ABL–induced leukemia. [Cancer Res 2009;69(16):6546–55]