tbuckley/cabot-search huggingface dataset:
Cell-Free 59 kDa Immunoreactive Integrin-Linked Kinase
Authors: Nuzhat Ahmed, Karen Oliva, Greg E Rice, Michael A Quinn
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We reported that the expression of integrin-linked kinase (ILK) is up-regulated in ovarian carcinomas and that ovarian cancer cells have high expression of ILK. In this study, we have examined the expression of cell-free 59 kDa immunoreactive (ir)ILK in the serum and peritoneal fluid (PTF) of patients with ovarian cancer and evaluated its potential as a serum biomarker for early-stage screening and for monitoring clinical status of patients after chemotherapy treatment. Experimental Design: Thirty-six serum specimens, including normal (n = 6), benign (n = 6), borderline (n = 4), grade 1 (n = 5), grade 2 (n = 5), and grade 3 (n = 10), were evaluated for the expression of irILK by Western blotting. The expression of irILK was evaluated in PTF (n = 10) and peritoneal washings from women with benign ovarian cysts (n = 4). In addition, tissue-conditioned medium obtained from the cultures of primary ovarian tumors (n = 9) was examined for the presence of irILK. Finally, the potential of serum irILK as a biomarker for ovarian cancer screening was evaluated by comparison with cancer antigen 125 (CA 125) concentrations in cancer patients before and after chemotherapy. Results: irILK expression was present in normal serum and in serum of patients with benign ovarian tumors. irILK expression was 6–9-fold higher in the serum of patients with grade 1, grade 2, and grade 3 ovarian cancer than in the serum of healthy volunteers and patients with benign ovarian tumors (P &amp;lt; 0.01). Enhanced expression of irILK in the serum of ovarian cancer patients correlated with the concentration of CA 125. High expression of irILK was present in all 10 PTF tested. Tissue-conditioned medium prepared from malignant ovarian tumors had 4-fold more irILK expression than conditioned medium obtained from borderline and benign tumors (P &amp;lt; 0.01). irILK expression in serum of cancer patients was reduced to basal normal levels after six cycles of Taxol/carboplatin and was consistent with the change of CA 125 levels before and after chemotherapy. Conclusions: These data suggest that irILK is an ovarian tumor-associated antigen and implicates its potential not only as a biomarker for early-stage screening but also as a marker for monitoring the clinical condition of patients after treatment.
The CETP <i>Taq</i>IB Polymorphism Is Associated With the Risk of Sudden Death in Type 2 Diabetic Patients
Authors: Isabelle Porchay-Baldérelli, Franck Péan, Naïma Bellili, Riphed Jaziri, Michel Marre, Frédéric Fumeron
Journal: Diabetes Care (2007)

Type 2 diabetic patients have a high risk of coronary heart disease (CHD) and sudden death. This cardiovascular risk can be partly attributed to low levels of HDL cholesterol. The B2 allele of the CETP TaqIB polymorphism has been repeatedly reported to be associated with high HDL cholesterol levels in both healthy and type 2 diabetic subjects, but its association with CHD is unclear. We investigated the association of the CETP TaqIB polymorphism with CHD, and sudden death in particular, in a prospective cohort of type 2 diabetic patients.The CETP TaqIB polymorphism was genotyped in 3,124 type 2 diabetic subjects with high cardiovascular risk: the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study. We used Cox regression analysis to estimate the impact of the TaqIB single nucleotide polymorphism on the CHD events (myocardial infarction or sudden death) during follow-up.The incidence of CHD was higher in B1B1 homozygotes than in B2 carriers (P = 0.02). This effect was mainly due to sudden death (hazard ratio [B1B1 vs. B2+] = 1.51 [95% CI = 1.05-2.18]). Although the B1 allele was associated in a dose-dependent fashion with lower HDL cholesterol (P < 0.001), the association with sudden death persisted after adjustment for multiple risk factors, including HDL cholesterol levels.In type 2 diabetic patients, the CETP TaqIB polymorphism is a good genetic predictor of cardiac mortality. This association is partly independent of the effect on HDL cholesterol levels.
Angiotensin II–Induced Stimulation of Smooth Muscle α-Actin Expression by Serum Response Factor and the Homeodomain Transcription Factor MHox
Authors: Martina B. Hautmann, Maria M. Thompson, Ellen A. Swartz, Eric N. Olson, Gary K. Owens
Journal: Circulation Research (1997)

Abstract The objective of the present study was to examine the molecular mechanisms whereby angiotensin II (Ang II) stimulates smooth muscle (SM) α-actin expression in rat aortic smooth muscle cells (SMCs). Nuclear run-on analysis and transfection studies indicated that the effects of Ang II on SM α-actin were mediated at least in part at the transcriptional level. Transfection of various rat SM α-actin promoter/chloramphenicol acetyltransferase (CAT) constructs into SMCs demonstrated that the first 155 bp of the SM α-actin promoter was sufficient to confer maximal Ang II responsiveness, conferring an ≈4-fold increase in reporter activities in these SMCs compared with vehicle-treated SMCs. Mutation of either of two highly conserved CArG elements, designated A (−62) and B (−112), completely abolished Ang II–induced increases in reporter activity, whereas mutation of a homeodomain-like binding sequence at −145 (ATTA) reduced reporter activity by half. Results of EMSAs showed that nuclear extracts from Ang II–treated SMCs exhibited enhanced binding activity of serum response factor (SRF) to the CArG elements and of a homeo-domain factor, MHox, to the ATTA element. Northern analyses showed that Ang II also stimulated marked increases in MHox mRNA levels. Western analyses demonstrated that Ang II–induced increases in SRF binding were not due to increased SRF protein expression. Recombinant MHox markedly enhanced binding activity of SRF in EMSAs. Finally, MHox overexpression transactivated a SM α-actin promoter/CAT reporter construct by ≈3.5-fold in transient cotransfection studies. These results provide evidence for involvement of a homeodomain transcription factor, MHox, in Ang II–mediated stimulation of SM α-actin via a CArG/SRF-dependent mechanism.
Omeprazole in the treatment of erosive oesophagitis refractory to high dose cimetidine and ranitidine.
Authors: K D Bardhan, P Morris, M Thompson, D S Dhande, R F Hinchliffe, R B Jones, M J Daly, N J Carroll
Journal: Gut (1990)

Forty five patients with refractory oesophagitis, defined as persisting erosive changes or ulceration despite a minimum of three months' treatment with cimetidine 3.2 g daily or ranitidine 0.9 g daily, were treated in an open trial with omeprazole 40 mg daily for up to eight weeks. Endoscopically defined healing was observed in 73% of patients after four weeks' treatment and in 91% after eight weeks' treatment. Symptoms were completely relieved in 60% of patients, improved in 34%, unchanged in 4%, and worsened in 2%. After healing patients returned to maintenance treatment with cimetidine 1.6-3.2 g daily, depending on the severity of their illness before treatment with omeprazole. By six months and 12 months only 55% and 33% of patients respectively were still in remission. This study suggests that when erosive oesophagitis is refractory to treatment with high dose cimetidine or ranitidine, treatment with omeprazole 40 mg daily for up to eight weeks is effective in inducing healing and relieving symptoms.
Androgen Deprivation Therapy and Cardiovascular Risk
Authors: Sanoj Punnen, Matthew R. Cooperberg, Natalia Sadetsky, Peter R. Carroll
Journal: Journal of Clinical Oncology (2011)

The potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to further elucidate the association between treatment selection and cause of mortality.A total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer-specific mortality (PCSM), CVM, and all-cause mortality. A propensity score-adjusted and a propensity-matched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments.Patients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT.Patients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.
Fasting and postprandial ileal function in adapted ileostomates and normal subjects.
Authors: S D Ladas, P E Isaacs, G M Murphy, G E Sladen
Journal: Gut (1986)

The output of 11 established ileostomies was compared with ileal flow measured by intestinal perfusion in five normal volunteers when fasting and during the ileal passage of test meals containing different proportions of medium chain triglyceride and long chain triglyceride. Oroileal transit of the meal was the same in the two groups, but ileostomy output was less than ileal flow of normal persons both fasting (16.3 +/- 10.9 vs 62.4 +/- 24.7 ml/h, p less than 0.001) and after the long chain triglyceride rich meal (35.4 27.0 vs 96.1 +/- 20.2 ml/h, p less than 0.001). After ingestion of the medium chain triglyceride rich meal, ideal flow failed to increase in normal subjects but in ileostomates the changes in flow after medium chain triglyceride and long chain triglyceride rich meals were not significantly different. The fasting ileostomy effluent composition differed from that of normal fasting ileal content in having a higher concentration of potassium (8.0 +/- 2.9 vs 4.7 +/- 0.6 mmol/1, p less than 0.04) and a higher osmolality (353 +/- 63 vs 287 +/- 5 mosm/kg, p less than 0.05). Sodium concentration tended to be lower in ileostomy effluent, but in contrast to previous reports, ileostomy effluent was of consistently alkaline pH (7.2 +/- 0.3). These concentrations were not significantly altered by either type of meal. The long chain triglyceride rich meal increased the ileal flow of bile acids in both normal subjects and ileostomates, whereas the medium chain triglyceride rich meal increased bile acid flow in ileostomates but not in normal subjects, possibly reflecting a different amount of the bile acids in the ileum of the ileostomate. In the adapted ileostomate, the low volume and high potassium concentration of fasting effluent suggest that sodium and water absorption are continuously stimulated by chronic salt depletion.
Pemphigus herpetiformis with IgG autoantibodies to desmoglein 1 and desmocollin 1
Authors: H.R. On, T. Hashimoto, S.-C. Kim
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Pemphigus herpetiformis (PH) is a rare variant of pemphigus that clinically resembles dermatitis herpetiformis and has immunopathological features of pemphigus.1 The clinical features include erythematous herpetiform papules, vesicles or pustules, which often appear in an annular pattern and are intensely pruritic. PH has a diverse histopathological pattern with eosinophilic spongiosis and intraepidermal or subcorneal microabscesses containing neutrophils and eosinophils.1 Most patients show IgG autoantibodies against the cell surfaces of keratinocytes.2 The target antigen is desmoglein (Dsg)1 in most cases and Dsg3 in the remainder, and the clinical and immunological findings of PH are closer to those of pemphigus foliaceus.1 3 Recently, antibodies against desmocollin (Dsc)1 and Dsc3, along with other autoantibodies, have been detected in some cases of PH.4 5 6 We report a case of PH with anti‐Dsg1 and anti‐Dsc1 antibodies. A 51‐year‐old man presented with a 1‐year history of pruritic vesicles on the trunk and extremities. He had previously been treated with cyclophosphamide and dapsone for a diagnosis of linear IgA dermatosis at another hospital. Routine laboratory tests showed no abnormal findings. On physical examination, multiple erythematous papules and vesicles were seen on the trunk and both legs (Fig. 1a,b). Histological examination of the skin biopsy specimen revealed intraepidermal vesicles filled with numerous neutrophils and eosinophils, as well as scant acantholytic cells. Perivascular mixed lymphohistiocytic and eosinophilic infiltration was seen in the upper dermis (Fig. 1c). Direct immunofluorescence (IF) showed IgG and C3 deposition on the cell surfaces of keratinocytes (Fig. 1d). Indirect IF of normal human skin demonstrated IgG deposition on the cell surfaces of keratinocytes at a titre of 1 : 40.
A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis
Authors: Richard L. Greenman
Journal: JAMA (1991)

To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis.Double-blind, randomized, placebo-controlled trial.Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals.Hospitalized adults with signs of gram-negative infection and a systemic septic response.Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later.Mortality over the 30-day study period, resolution of organ failures, and safety.Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified.Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.
Calmodulin: a gatekeeper for ryanodine receptor function in the myocardium
Authors: M. Puceat
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure’, by M. Ono et al. , pp. 609–617, this issue. 

The ryanodine receptor (RyR) releases intracellular Ca2+ from the sarcoplasmic reticulum (SR) of beating cardiomyocytes following Ca2+ influx via the voltage-dependent sarcolemmal Ca2+ channel. This crucial cellular event, named ‘Ca2+-induced Ca2+ release' and discovered three decades ago by Fabiato and Fabiato,1 is mandatory for the rhythmic contraction as well as for maintaining the force–frequency relationship of the myocardium. RyR type 1 (RyR1), cardiac RyR2, and RyR3 have been the subject of intensive investigation for many years. More recently, Ikemoto and Yamamoto provided evidence of structure–function relationships in the RyRs. They reported that the N-terminal and central domains of RyRs form an interacting domain pair. Unzipping and zipping actions of such a domain pair determines the opening and closing probabilities of the RyR Ca2+ channel, respectively.2 A dysregulation of this domain pair leads to a defect in heart function. Unzipping the N-terminal from the central domain leads to RyR2 hyperactivation and Ca2+ leak from the SR, … 

*Corresponding author. Tel: +33 160 878 923; fax: +33 160 878 999, Email: michel.puceat{at}inserm.fr
Microbiota-Mediated Inflammation and Antimicrobial Defense in the Intestine
Authors: Silvia Caballero, Eric G. Pamer
Journal: Annual Review of Immunology (2015)

The diverse microbial populations constituting the intestinal microbiota promote immune development and differentiation, but because of their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized and mysterious. In the last decade, deep nucleic acid sequencing platforms, new computational and bioinformatics tools, and full-genome characterization of several hundred commensal bacterial species facilitated studies of the microbiota and revealed that differences in microbiota composition can be associated with inflammatory, metabolic, and infectious diseases, that each human is colonized by a distinct bacterial flora, and that the microbiota can be manipulated to reduce and even cure some diseases. Different bacterial species induce distinct immune cell populations that can play pro- and anti-inflammatory roles, and thus the composition of the microbiota determines, in part, the level of resistance to infection and susceptibility to inflammatory diseases. This review summarizes recent work characterizing commensal microbes that contribute to the antimicrobial defense/inflammation axis.
Peginterferon-α2a and Ribavirin Combination Therapy in Chronic Hepatitis C
Authors: Stephanos J. Hadziyannis
Journal: Annals of Internal Medicine (2004)

Background: Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. Objective: To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-α2a plus a low or standard dose of ribavirin. Design: Randomized, double-blind trial. Setting: 99 international centers. Patients: 1311 patients with chronic hepatitis C. Intervention: Peginterferon-α2a, 180 µg/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. Measurement: Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. Results: Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-α2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. Conclusion: Treatment with peginterferon-α2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks. *Members of the PEGASYS International Study Group are listed in the Appendix.
The pinocytic rate of activated macrophages.
Authors: P J Edelson, R Zwiebel, Z A Cohn
Journal: The Journal of Experimental Medicine (1975)

Peritoneal macrophages from mice injected 4 days previously with Brewer's thioglycollate medium have a pinocytic rate, in culture, of 190 ng horseradish peroxidase (HRP)/100 mug cell protein/h, compared to the rate of resident peritoneal cells of 53 ng HRP/100 mug cell protein/h. Mice injected with endotoxin or with only certain of the components of the Brewer's medium show an intermediate level of stimulation. The rate of unstimulated, endotoxin-stimulated, or thioglycollate-stimulated cells shows little change over several days in culture. The pinocytic rate of thioglycollate-stimulated cells can, however, be further increased by exposure of concanavalin A. Although cells may show transient increases in their pinocytic rate in many situations, a sustained increase in pinocytic rate is a sign of the "activated" state of macrophages.
International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 Report
Authors: John K. Field, Robert A. Smith, Denise R. Aberle, Matthijs Oudkerk, David R. Baldwin, David Yankelevitz, Jesper Holst Pedersen, Scott James Swanson, William D. Travis, Ignacio I. Wisbuba, Masayuki Noguchi, Jim L. Mulshine
Journal: Journal of Thoracic Oncology (2011)
Parahippocampal Volume Deficits in Subjects With Aging-Associated Cognitive Decline
Authors: Johannes Pantel, Benita Kratz, Marco Essig, Johannes Schröder
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Neuropathological evidence suggests that the earliest changes in Alzheimer's disease selectively affect the parahippocampal regions of the brain. This study was conducted to determine if otherwise healthy elderly subjects with mild cognitive impairment had structural volume deficits affecting the parahippocampal gyrus. METHOD: Magnetic resonance imaging (MRI) was used to compare global and regional brain volumes in 21 subjects with mild cognitive deficits defined according to the criteria for aging-associated cognitive decline, 22 cognitively intact comparison subjects, and 12 patients with Alzheimer's disease. RESULTS: Compared with the cognitively intact subjects, the subjects with aging-associated cognitive decline had a significantly smaller mean volume of the right parahippocampal gyrus. The subjects with aging-associated cognitive decline had a mean parahippocampal volume that was intermediate between that of the Alzheimer's disease patients and that of the cognitively intact subjects. CONCLUSIONS: Parahippocampal atrophy underlies the observed cognitive deficits in aging-associated cognitive decline. These findings support the hypothesis that aging-associated cognitive decline represents a preclinical stage of Alzheimer's disease.