tbuckley/cabot-search huggingface dataset:
Protein Kinase C Modulates Ventilatory Patterning in the Developing Rat
Authors: HARI P. R. BANDLA, NARONG SIMAKAJORNBOON, GAVIN R. GRAFF, DAVID GOZAL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Protein kinase C (PKC) mediates important components of signal transduction pathways underlying neuronal excitability and modulates respiratory timing mechanisms in adult rats. To determine ventilatory effects of systemic PKC inhibition during development, whole-body plethysmographic recordings were conducted in 2–3-d (n = 11), 5–6-d (n = 19), 10–12-d (n = 14), and 20–21-d-old (n = 14) rat pups after treatment with vehicle and Ro 32-0432 (100 mg/kg, intraperitoneally). Ro 32-0432 decreased minute ventilation (V˙ e) by 51.0 ± 5.5% (mean ± SEM) in youngest pups (p < 0.01) but only 19.1 ± 6.8% in 20–21-d-old pups (p < 0.01). V˙ e decreases were always due to frequency reductions with tidal volume (Vt) remaining unaffected. Respiratory rate decreases primarily resulted from marked expiratory time (Te) prolongations being more pronounced in 2–3-d-old (115.5 ± 28.9%) compared with 20–21-d old (36.6 ± 10.9%; p < 0.002 analysis of variance [ANOVA] ). Expression of the PKC isoforms α , β , γ , δ , ι , and μ was further examined in brainstem and cortex by immunoblotting and revealed different patterns with postnatal age and location. We conclude that endogenous PKC inhibition elicits age-dependent ventilatory reductions which primarily affect timing mechanisms rather than changes in volume drive. This effect on ventilation abates with increasing postnatal age suggesting that the neural substrate mediating overall respiratory output may be more critically dependent on PKC activity in the immature animal.
Combined Use of a Fasting Plasma Glucose Concentration and HbA1c or Fructosamine Predicts the Likelihood of Having Diabetes in High-Risk Subjects
Authors: Gary T C Ko, Juliana C N Chan, Vincent T F Yeung, Chun-Chung Chow, Lynn W W Tsang, June K Y Li, Wing-Yi So, Hendena P S Wai, Clive S Cockram
Journal: Diabetes Care (1998)

OBJECTIVE To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG ≥ 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) ≥ 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG ≥ 5.6 mmol/l and an HbA1c ≥ 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG ≥ 5.4 mmol/l and a fructosamine ≥ 235 μmol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG ≥ 5.6 mmol/l and &amp;lt; 7.8 mmol/l and a fructosamine ≥235 μmol/1 (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408 – 526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/1, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach ∼ 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.
Multiple Structural Elements in Voltage-Dependent Ca2+ Channels Support Their Inhibition by G Proteins
Authors: Ji-Fang Zhang, Patrick T Ellinor, Richard W Aldrich, Richard W Tsien
Journal: Neuron (1996)

Molecular determinants of Ca2+ channel responsiveness to inhibition by receptor-coupled G proteins were investigated in Xenopus oocytes. The inhibitory response of α1B (N-type) channels was much larger than α1A (P/Q-type) channels, while α1C (L-type) channels were unresponsive. Differences in both degree and speed of inhibition were accounted for by variations in inhibitor off-rate. We tested proposals that inhibitory G protein and Ca2+ channel β subunits compete specifically at the I-II loop. G protein–mediated inhibition remained unaltered in α1B subunits containing a point mutation in the I-II loop segment critical for Ca2+ channel β subunit binding, and in chimeras where the I-II loop of α1B was replaced with counterparts from α1A or α1C. Full interconversion between modulatory behaviors of α1B and α1A was achieved only by swapping both motif I and the C-terminus in combination. Thus, essential structural elements for G protein modulation reside in multiple Ca2+ channel domains.
Effect of codeine and loperamide on upper intestinal transit and absorption in normal subjects and patients with postvagotomy diarrhoea.
Authors: J D O'Brien, D G Thompson, A McIntyre, W R Burnham, E Walker
Journal: Gut (1988)

Patients with chronic severe diarrhoea after truncal vagotomy and pyloroplasty are often difficult to treat using conventional antidiarrhoeal drugs and remain severely disabled. We examined the effect of two drugs, codeine phosphate and loperamide, on upper intestinal transit and carbohydrate absorption, measured non-invasively by serial exhaled breath hydrogen monitoring, in patients with postvagotomy diarrhoea who had previously failed to gain relief from drug therapy. Orocaecal transit was consistently faster in these patients than a group of controls and was associated with malabsorption of glucose. Codeine phosphate 60 mg significantly delayed transit in patients and controls and was associated with a reduction in glucose malabsorption and improvement in symptoms. Loperamide also delayed transit and improved symptoms, but the doses required for this effect (12-24 mg) were higher than usually considered necessary in secretory diarrhoea. These studies indicate that rapid intestinal nutrient transit and associated malabsorption is a factor in the development of diarrhoea postvagotomy and that symptomatic relief can be achieved in most patients by more rational use of existing drugs.
Abstract 1511: Stromal gene signature regulated by TGFβ signaling predicts poor clinical outcome in ovarian cancer .
Authors: Dong-Joo Cheon, Yunguang Tong, Myung-Shin Sim, Xiaojiang Cui, Dror Berel, Mourad Tighiouart, Wolf Ruprecht Wiedemeyer, Beth Karlan, Sandra Orsulic
Journal: Cancer Research (2013)

Abstract Despite the clinical and histopathological similarities in initial disease presentation, patients with advanced ovarian cancer rapidly develop chemoresistance and succumb to the disease. In order to identify genes that are associated with poor patient survival, we analyzed microarray datasets of 795 advanced ovarian cancer patients and correlated gene expression levels with clinical data. We identified a 60-gene signature that was strongly associated with poor survival. Many genes in the signature were stromal genes, including POSTN, FN1, COL11A1, COL6A1, COL3A1, LOX, TIMP3, and VCAN. The same stromal signature was enriched in ovarian cancer metastases and in a cisplatin-resistant A2780 human ovarian cancer cell line. Expression of many stromal genes was induced by TGFβ1 and the effect was reversed by A83-01, a potent TGFβ1 inhibitor. Interestingly, we found that ovarian cancer stem cells (CSC) also express TGFβR2 and several TGFβ1-target genes, including COL6A1 and COL3A1, which were previously implicated in cisplatin resistance. Culturing of A2780 cells on collagen substrate resulted in increased cisplatin resistance and expansion of the CSC population. Our results suggest that TGFβ1 signaling induces stromal gene expression and forms a favorable microenvironment for ovarian CSC, thereby leading to cisplatin resistance and poor patient survival. Citation Format: Dong-Joo Cheon, Yunguang Tong, Myung-Shin Sim, Xiaojiang Cui, Dror Berel, Mourad Tighiouart, Wolf Ruprecht Wiedemeyer, Beth Karlan, Sandra Orsulic. Stromal gene signature regulated by TGFβ signaling predicts poor clinical outcome in ovarian cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1511. doi:10.1158/1538-7445.AM2013-1511
164 Single pass albumin dialysis (SPAD) in liver failure with commercial albumin is associated with octanoate and tryptophane intoxication
Authors: J. Stange, S. Koball, J. Hentschel, M. Gloger, S. Klammt, H. Hickstein, K. Arndt, M. Suraj, R. Schmidt
Journal: Journal of Hepatology (2006)
London needs to reconfigure its HIV services, says Civitas report
Authors: J. Wise
Journal: BMJ (2011)

London’s healthcare services for people infected with HIV have been inefficiently managed for years and should be reconfigured, with greater involvement of primary care, concludes a report by the social policy think tank Civitas after interviewing specialists in HIV.

The report argues that the United Kingdom’s coalition government is failing to realise cost savings that could also improve the quality of care. It says that specialist services, such as those for patients with HIV, could be reformed without the need for the costly overhaul of NHS commissioning as a whole.

James Gubb, director of the Civitas health unit and a coauthor of the report, …
Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat
Authors: Mary E. Gilbert, Li Sui
Journal: Environmental Health Perspectives (2008)

BackgroundPerchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development.ObjectivesThe purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate.MethodsPregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus.ResultsAt the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose.ConclusionsDose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate.
Oral Dextran Sulfate (UAOO1) in the Treatment of the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex
Authors: Donald I. Abrams
Journal: Annals of Internal Medicine (1989)

Study Objective: To evaluate the tolerance and safety of oral dextran sulfate (UAOO1), a potent in-vitro inhibitor of human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Design: Unblinded, dose-escalation 8-week trial. Setting: An AIDS outpatient clinic of a university-affiliated municipal hospital. Patients: Thirty-four patients with stage III or IV HIV infection were enrolled. Five patients in six different dosage cohorts completed the study. The population was predominantly homosexual men with persistent generalized lymphadenopathy (stage III). Interventions: Oral dextran sulfate was given three times daily in total daily doses of 900 to 5400 mg for 8 weeks. Patients were monitored for tolerance and toxicity. Immunologic and virologic values were also followed. Measurements and Main Results: Oral dextran sulfate was given without significant side effects. The commonest minor subjective complications were mental hyperexcitability and gastrointestinal complaints. The most frequent laboratory abnormalities were leukopenia and hepatic transaminase elevations. Eleven patients required dose reductions, and therapy was stopped in 4 because of toxicities. The CD4 lymphocyte numbers did not change appreciably. No decline in beta-2 microglobulin levels occurred. The HIV antigen levels were unchanged from baseline. No assay for dextran sulfate plasma levels has yet proven successful. Conclusions: Oral dextran sulfate appears to be well tolerated. No evidence of systemic absorption of the parent compound is available. However, in view of the promising invitro effects and acceptable toxicity, oral dextran sulfate as a potential antiretroviral agent continues to be studied.
Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C
Authors: Marcus Wiedmann, Uwe G. Liebert, Ute Oesen, Heiner Porst, Manfred Wiese, Sabine Schroeder, Ulrich Halm, Joachim Mössner, Frieder Berr
Journal: Hepatology (2000)

The immunogenicity of hepatitis B vaccine is unknown for patients with chronic hepatitis C, although hepatitis B vaccination is highly recommended in these patients. We therefore studied in a prospective open trial of 59 patients with chronic hepatitis C (mean age 42 years, hepatitis C for >10 years, Child-Pugh score < or = 5) and 58 healthy hospital staff persons the rate of nonresponse (anti-HBs <10 mIU/mL at 9 months) to recombinant hepatitis B vaccine (Gen H-B-Vax(R),10 microg intradeltoidal at month 0, 1, and 6). Nonresponse was observed in 18/59 (31%) patients with chronic hepatitis C and 5/58 (9%) healthy staff persons (P <.005) (vs. 7% in historical controls; P <.005), low response (anti-HBs 10-99 mIU/mL) in 19% of patients with chronic hepatitis C and 17% of staff persons. High-dose booster vaccination led to seroconversion in 12/15 (80%) of primary nonresponders. Primary nonresponse to HB vaccine was related neither to presence of early-stage liver cirrhosis nor magnitude of serum hepatitis C virus (HCV) RNA concentration, nor explained by the presence of human leukocyte antigen (HLA) types (B8 DR3, B44, DR7, DQ2) predisposing to low antibody response to hepatitis B surface antigen. The rate of primary nonresponse to the standard regimen of recombinant hepatitis B vaccine is surprisingly high in patients with longstanding chronic hepatitis C. Therefore, the antibody to HBV surface antigen (anti-HBs) titer response should be determined in these patients. Depending on the response titer, higher booster doses may be required to achieve and maintain seroprotection in these patients.
Spatiotemporal Development and Distribution of Intercellular Junctions in Adult Rat Cardiomyocytes in Culture
Authors: Sawa Kostin, Stefan Hein, Erwin P. Bauer, Jutta Schaper
Journal: Circulation Research (1999)

The mode of development of the intercalated disk (ID) is largely unknown, and the hypothesis was tested that the assembly of cell adhesion junctions may precede the formation of gap junctions (GJ) in developing ID in adult rat cardiomyocyte (ARC) in long-term culture. Immunostaining for connexin 43 (Cx43) and for cell adhesion junction proteins (N-cadherin, catenins, and desmoplakin) in single- and double-label techniques was analyzed and quantified by confocal and electron microscopy. All proteins investigated disappeared 48 hours after ARC isolation and reappeared parallel to redifferentiation of ARC. The newly formed ID, observed after 5 days, showed the presence of N-cadherin, catenins, and desmoplakin, low levels of Cx43, and absence of ultrastructurally discernible gap junctions. A progressive incorporation of Cx43 within ID was observed after 6 days, when cell adhesion junction proteins were already organized as zipper-like structures. Quantitative confocal analysis revealed a progressive augmentation of the fluorescence intensity of Cx43, associated with an increase in both the number and size of GJ, resulting in a substantial increase in the percentage of total GJ length per reassembled ID from 1.67% (day 6) to 15.58% (day 12). In the present study, we show that (1) the formation of the ID can be followed in ARC in culture and (2) the assembly of the adhering type of junction is the prerequisite for subsequent GJ formation within the ID. These findings may have clinical relevance in elaborating strategies for using myocardial grafts and for the potential restoration of GJ communication in cardiac diseases.
Abstract 1846: Potential of tumor-suppressive <i>miR-596</i> targeting <i>LGALS3BP</i> as a therapeutic agent in oral cancer.
Authors: Ken-ichi Kozaki, Hironori Endo, Tomoki Muramatsu, Mayuko Furuta, Narikazu Uzawa, Atiphan Pimkhaokham, Teruo Amagasa, Johji Inazawa
Journal: Cancer Research (2013)

Abstract The incidence and mortality statistics for oral squamous cell carcinoma (OSCC) were 10th and 12th, respectively, in human cancers diagnosed worldwide in 2008. In this study, to identify novel tumor-suppressive microRNAs (TS-miRNAs) and their direct targets in OSCC, we performed methylation-based screening for 43 miRNAs encoded by 46 miRNA genes located within 500bp downstream of 40 CpG islands and genome-wide gene expression profiling in combination with a prediction database analysis, respectively, in 18 cell lines, resulting in the identification of a novel TS-miRNA miR-596 directly targeting LGALS3BP/Mac-2 BP/90K. DNA hypermethylation of CpG island located 5’-upstream of miR-596 gene was frequently observed in OSCC cell lines (100% of 18 cell lines) and primary OSCC cases (46.2% and 76.3% of 26 Japanese and 38 Thais primary cases) in a tumor-specific manner. The ectopic transfection of double-stranded RNA (dsRNA) mimicking miR-596 or specific siRNA for LGALS3BP significantly induced growth inhibition and apoptosis in cell lines lacking miR-596 expression or overexpressing LGALS3BP, respectively, in a manner associated with a suppression of ERK1/2 phosphorylation. Moreover, we also mention the effect of dsRNA mimicking miR-596 on the growth of an OSCC cell line in vivo. Our findings define a central role for miR-596 in OSCC and suggest the potential of miR-596 as an anti-cancer agent for miRNA replacement therapy in OSCC. Citation Format: Ken-ichi Kozaki, Hironori Endo, Tomoki Muramatsu, Mayuko Furuta, Narikazu Uzawa, Atiphan Pimkhaokham, Teruo Amagasa, Johji Inazawa. Potential of tumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1846. doi:10.1158/1538-7445.AM2013-1846
Predictors of virologic relapse in patients with chronic hepatitis C (CHC) treated with peginterferon alfa-2a (40KD) (pegasys) alone or in combination with ribavirin (copegus)
Authors: V. Balan, S. Zeuzem, H. Sette, M. Fried, D. Jensen, G. Pastore, P. Marcellin, F. Sedarati
Journal: Journal of Hepatology (2003)
A new sensitive method for the quantification of internal carotid stenoses by means of ultrasound Doppler signal processing
Authors: K PAULAT, P PAUSCHINGER, M POPP, M SCHIEBE, B WIDDER
Journal: Cardiovascular Research (1985)

A new way of processing the ultrasound Doppler spectrum is presented. By introducing a Disturbance Index (DI), based on a double Fourier transformation, the quantitative evaluation of blood flow disturbance is possible. The integral value of this index over the whole cardiac cycle can be used to quantify the degree of lower grade internal carotid artery (ICA) stenoses and plaques. In a preliminary study, this new method has been tested in 18 normal and 10 atherosclerotic carotid arteries against Duplex-scan and angiography. The results were compared with 5 alternative methods of processing the Doppler spectrum.
A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and <sup>90</sup>yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B‐cell non‐Hodgkin lymphoma
Authors: Thomas E. Witzig, Gregory A. Wiseman, Matthew J. Maurer, Thomas M. Habermann, Ivana N.M. Micallef, Grzegorz S. Nowakowski, Stephen M. Ansell, Joseph P. Colgan, David J. Inwards, Luis F. Porrata, Brian K. Link, Clive S. Zent, Patrick B. Johnston, Tait D. Shanafelt, Cristine Allmer, Yan W. Asmann, Mamta Gupta, Zuhair K. Ballas, Brian J. Smith, George J. Weiner
Journal: American Journal of Hematology (2013)

Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial, we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m(2) days 1,8, and 15; (111) In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of (90) Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hr without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation.