tbuckley/cabot-search huggingface dataset:
The Effect of Rosiglitazone on Overweight Subjects With Type 1 Diabetes
Authors: Suzanne M. Strowig, Philip Raskin
Journal: Diabetes Care (2005)

OBJECTIVE—To evaluate the safety and effectiveness of rosiglitazone in the treatment of overweight subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 50 adult type 1 diabetic subjects with a baseline BMI ≥27 kg/m2 were randomly assigned in a double-blind fashion to take insulin and placebo (n = 25) or insulin and rosiglitazone 4 mg twice daily (n = 25) for a period of 8 months. Insulin regimen and dosage were modified in all subjects to achieve near-normal glycemic control. RESULTS—Both groups experienced a significant reduction in HbA1c (A1C) level (rosiglitazone: 7.9 ± 1.3 to 6.9 ± 0.7%, P &amp;lt; 0.0001; placebo: 7.7 ± 0.8 to 7.0 ± 0.9%, P = 0.002) and a significant increase in weight (rosiglitazone: 97.2 ± 11.8 to 100.6 ± 16.0 kg, P = 0.008; placebo: 96.4 ± 12.2 to 99.1 ± 15.0, P = 0.016). Baseline measures of BMI (P = 0.001), total daily insulin dose (P = 0.002), total cholesterol (P = 0.005), HDL cholesterol (P = 0.00l), and LDL cholesterol (P = 0.02) were predictors of improvement in A1C level only in the group treated with rosiglitazone. Total daily insulin dose increased in subjects taking placebo (74.0 ± 33.8 to 82.0 ± 48.9 units, P &amp;lt; 0.05 baseline vs. week 32), but it decreased slightly in subjects taking rosiglitazone (77.5 ± 28.6 to 75.3 ± 33.1 units). Both systolic blood pressure (137.4 ± 15.6 vs. 128.8 ± 14.8 mmHg, baseline vs. week 32, P &amp;lt; 0.02) and diastolic blood pressure (87.2 ± 9.4 vs. 79.4 ± 7.2 mmHg, P &amp;lt; 0.0001) improved in the group treated with rosiglitazone. The total incidence of hypoglycemia did not differ between groups. CONCLUSIONS—Rosiglitazone in combination with insulin resulted in improved glycemic control and blood pressure without an increase in insulin requirements, compared with insulin- and placebo-treated subjects, whose improved glycemic control required an 11% increase in insulin dose. Weight gain and hypoglycemia were similar in both groups at the end of the study. The greatest effect of rosiglitazone occurred in subjects with more pronounced markers of insulin resistance.
Bronchial vascular remodelling in patients with COPD and its relationship with inhaled steroid treatment
Authors: A Zanini, A Chetta, M Saetta, S Baraldo, C Castagnetti, G Nicolini, M Neri, D Olivieri
Journal: Thorax (2009)

Only a few studies have evaluated microvascular changes and proangiogenetic mediators in the bronchial mucosa of patients with chronic obstructive pulmonary disease (COPD), and the results have been discordant. Furthermore, the role of inhaled corticosteroids (ICS) in COPD has not been extensively studied. A study was undertaken to evaluate vascular remodelling, its relationship with inflammatory cells and treatment effects in the bronchial mucosa of patients with COPD.The study comprised three groups: (1) 10 non-treated patients with COPD (COPD); (2) 10 patients with COPD treated with nebulised beclomethasone dipropionate 1600-2400 mug daily (equivalent to 800-1200 mug via metered dose inhaler) (COPD/ICS); and (3) 8 control subjects (CS). Bronchial biopsies were evaluated for number and size of vessels and vascular area. Specimens were also examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) expression and inflammatory cell counts were performed.Vascular area, vessel size, VEGF+ cells, bFGF+ cells and TGF-beta+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (all p<0.05). In addition, bFGF+ cells were significantly increased in the COPD/ICS group compared with the CS group, and CD8+ and CD68+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (p<0.05). In the COPD group the VEGF+ cells correlated with the number of vessels (p<0.05), vascular area (p<0.01) and vessel size (p<0.05), and TGF-beta+ cells correlated significantly with vascular area (p<0.05).Bronchial vascular remodelling in patients with COPD is mainly related to morphological changes of the mucosal microvessels rather than to new vessel formation, and may be reduced in patients treated with steroids.
T cell cytotoxicity to Epstein-Barr virus infected B cells: comparison of patients with rheumatoid arthritis and their HLA identical siblings.
Authors: V R Winrow, J Norton, E J Holborow, H E Stierle, A Young, J A Sachs
Journal: Annals of the Rheumatic Diseases (1988)

Specific T cell cytotoxicity to Epstein-Barr virus (EBV) infected B cells is reported to be abnormal in rheumatoid arthritis (RA). The regression phenomenon was used to determine whether the immunoregulatory defect in RA is restricted to T cells, B cells, or HLA type. Peripheral blood T and B cells from patients with RA and their HLA identical healthy siblings were mixed in varying ratios with and without EBV, and thymidine incorporation was measured on days 7, 14, and 21. The results suggest that the T cell abnormality is related to disease activity and that an inherent defect exists in the rheumatoid B cell which is independent of disease activity.
Zinc transporter Znt5/Slc30a5 is required for the mast cell–mediated delayed-type allergic reaction but not the immediate-type reaction
Authors: Keigo Nishida, Aiko Hasegawa, Susumu Nakae, Keisuke Oboki, Hirohisa Saito, Satoru Yamasaki, Toshio Hirano
Journal: The Journal of Experimental Medicine (2009)

Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency. However, it remains unknown how Zn homeostasis is regulated in mast cells and if Zn transporters are involved in allergic reactions. We show that Znt5/Slc30a5 is required for contact hypersensitivity and mast cell–mediated delayed-type allergic response but not for immediate passive cutaneous anaphylaxis. In mast cells from Znt5−/− mice, Fcε receptor I (FcεRI)–induced cytokine production was diminished, but degranulation was intact. Znt5 was involved in FcεRI-induced translocation of protein kinase C (PKC) to the plasma membrane and the nuclear translocation of nuclear factor κB. In addition, the Zn finger–like motif of PKC was required for its plasma membrane translocation and binding to diacylglycerol. Thus, Znt5 is selectively required for the mast cell–mediated delayed-type allergic response, and it is a novel player in mast cell activation.
Long-Term Effectiveness of Supported Employment: 5-Year Follow-Up of a Randomized Controlled Trial
Authors: Holger Hoffmann, Dorothea Jäckel, Sybille Glauser, Kim T. Mueser, Zeno Kupper
Journal: American Journal of Psychiatry (2014)

The individual placement and support model of supported employment has been shown to be more effective than other vocational approaches in improving competitive work over 1-2 years in persons with severe mental illness. The authors evaluated the longer-term effects of the model compared with traditional vocational rehabilitation over 5 years.A randomized controlled trial compared supported employment to traditional vocational rehabilitation in 100 unemployed persons with severe mental illness. Competitive work and hospital admissions were tracked for 5 years, and interviews were conducted at 2 and 5 years to assess recovery attitudes and quality of life. A cost-benefit analysis compared program and total treatment costs to earnings from competitive employment.The beneficial effects of supported employment on work at 2 years were sustained over the 5-year follow-up period. Participants in supported employment were more likely to obtain competitive work than those in traditional vocational rehabilitation (65% compared with 33%), worked more hours and weeks, earned more wages, and had longer job tenures. Reliance on supported employment services for retaining competitive work decreased from 2 years to 5 years for participants in supported employment. Participants were also significantly less likely to be hospitalized, had fewer psychiatric hospital admissions, and spent fewer days in the hospital. The social return on investment was higher for supported employment participants, whether calculated as the ratio of work earnings to vocational program costs or of work earnings to total vocational program and mental health treatment costs.The results demonstrate that the greater effectiveness of supported employment in improving competitive work outcomes is sustained beyond 2 years and suggest that supported employment programs contribute to reduced hospitalizations and produce a higher social return on investment.
Expression of <i>CDK4</i> or <i>CDK2</i> in Mouse Oral Cavity Is Retained in Adult Pituitary with Distinct Effects on Tumorigenesis
Authors: Everardo Macias, Paula L. Miliani de Marval, Adrian Senderowicz, John Cullen, Marcelo L. Rodriguez-Puebla
Journal: Cancer Research (2008)

Abstract The keratin 5 (K5) promoter drives transgenic expression to the basal cell layer of stratified epithelia. Surprisingly, analysis of K5CDK4 and K5CDK2 transgenic mouse embryos showed CDK4 and CDK2 expression not only in the expected tissues, but also in the adenohypophysis. This organ is derived from an upwards growth of the primitive oropharnyx, a K5-expressing tissue. We show that transgenic expression of CDKs in the embryonic oral ectoderm is specifically retained in undifferentiated cells from the pars intermedia of the adenohypophysis. Interestingly, we found that K5CDK4 mice show a decreased number of pituitary stem cells, even though CDK4 is not expressed in the stem cells but in transit-amplifying (TA)–like cells. Interestingly, CDK4-expressing cells, but not CDK2-expressing cells, strongly synergize with lack of p27Kip1 to generate pituitary carcinomas that appear with shortened latency and are drastically more aggressive than those arising in p27−/− mice. Thus, we show that deregulation of CDK expression in the primitive oral epithelium plays a unique function, providing a selective advantage that gives rise to transgene-positive TA-like pituitary cells. Furthermore, retention of CDK4 in these TA-like pituitary cells synergizes with loss of p27Kip1 to induce pituitary adenocarcinomas. This model suggests that forced expression of CDK4 sensitizes cells and synergizes with a second change resulting in tumor development. [Cancer Res 2008;68(1):162–71]
Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in combination with sorafenib
Authors: Didier Roulin, Laurent Waselle, Anne Dormond-Meuwly, Marc Dufour, Nicolas Demartines, Olivier Dormond
Journal: Molecular Cancer (2011)

Abstract Background Targeted therapies for metastatic renal cell carcinoma (RCC), including mammalian target of rapamycin (mTOR) inhibitors and small-molecule multikinase inhibitors, have produced clinical effects. However, most patients acquire resistance over time. Thus, new therapeutic strategies need to be developed. Here, we evaluated the effect of the dual PI3K/mTOR inhibitor NVP-BEZ235, in combination with the multikinase inhibitor sorafenib on renal cancer cell proliferation and survival in vitro as well as on tumor growth in vivo . Methods The renal carcinoma cell lines 786-0 and Caki-1 were treated with NVP-BEZ235 or sorafenib, either alone or in combination. Tumor cell proliferation and apoptosis were investigated in vitro . The anticancer efficacy of NVP-BEZ235 alone, or in combination with sorafenib, was also evaluated on RCC xenografts in nude mice. Results Treatment of 786-0 and Caki-1 cells with NVP-BEZ235 or sorafenib resulted in reduced tumor cell proliferation and increased tumor cell apoptosis in vitro . The combination of NVP-BEZ235 and sorafenib was more effective than each compound alone. Similarly, in vivo , NVP-BEZ235 or sorafenib reduced the growth of xenografts generated from 786-0 or Caki-1 cells. The antitumor efficacy of NVP-BEZ235 in combination with sorafenib was superior to NVP-BEZ235 or sorafenib alone. Conclusions Our findings indicate that the simultaneous use of NVP-BEZ235 and sorafenib has greater antitumor benefit compared to either drug alone and thus provides a treatment strategy in RCC.
Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3
Authors: J Ma, M N Pollak, E Giovannucci, J M Chan, Y Tao, C H Hennekens, M J Stampfer
Journal: JNCI Journal of the National Cancer Institute (1999)

Insulin-like growth factor-I (IGF-I) is a potent mitogen for normal and neoplastic cells, whereas IGF-binding protein-3 (IGFBP-3) inhibits cell growth in many experimental systems. Acromegalics, who have abnormally high levels of growth hormone and IGF-I, have higher rates of colorectal cancer. We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospective case-control study nested in the Physicians' Health Study.Plasma samples were collected at baseline from 14916 men without diagnosed cancer. IGF-I, IGF-II, and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects. All P values are two-sided.IGFBP-3 levels correlated with IGF-I levels (r=.64) and with IGF-II levels (r=.90). After controlling for IGFBP-3, age, smoking, body mass index (weight in kg/[height in m]2), and alcohol intake, men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile (relative risk [RR]=2.51; 95% confidence interval [CI]=1.15-5.46; P for trend = .02). After controlling for IGF-I and other covariates, men with higher IGFBP-3 had a lower risk (RR=0.28; 95% CI=0.12-0.66; P for trend = .005, comparing extreme quintiles). The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men. IGF-II was not associated with risk.Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer.
Host Circadian Clock as a Control Point in Tumor Progression
Authors: Elisabeth Filipski, Verdun M King, XiaoMei Li, Teresa G Granda, Marie-Christine Mormont, XuHui Liu, Bruno Claustrat, Michael H Hastings, Francis Lévi
Journal: JNCI Journal of the National Cancer Institute (2002)

The circadian timing system controlled by the suprachiasmatic nuclei (SCN) of the hypothalamus regulates daily rhythms of motor activity and adrenocortical secretion. An alteration in these rhythms is associated with poor survival of patients with metastatic colorectal or breast cancer. We developed a mouse model to investigate the consequences of severe circadian dysfunction upon tumor growth.The SCN of mice were destroyed by bilateral electrolytic lesions, and body activity and body temperature were recorded with a radio transmitter implanted into the peritoneal cavity. Plasma corticosterone levels and circulating lymphocyte counts were measured (n = 75 with SCN lesions, n = 64 sham-operated). Complete SCN destruction was ascertained postmortem. Mice were inoculated with implants of Glasgow osteosarcoma (n = 16 with SCN lesions, n = 12 sham-operated) or pancreatic adenocarcinoma (n = 13 with SCN lesions, n = 13 sham-operated) tumors to determine the effects of altered circadian rhythms on tumor progression. Time series for body temperature and rest-activity patterns were analyzed by spectral analysis and cosinor analysis. Parametric data were compared by the use of analysis of variance (ANOVA) and survival curves with the log-rank test. All statistical tests were two-sided.The 24-hour rest-activity cycle was ablated and the daily rhythms of serum corticosterone level and lymphocyte count were markedly altered in 75 mice with complete SCN destruction as compared with 64 sham-operated mice (two-way ANOVA for corticosterone: sampling time effect P<.001, lesion effect P =.001, and time x lesion interaction P<.001; for lymphocytes P =.001,.002, and.002 respectively). Body temperature rhythm was suppressed in 60 of the 75 mice with SCN lesions (P<.001). Both types of tumors grew two to three times faster in mice with SCN lesions than in sham-operated mice (two-way ANOVA: P<.001 for lesion and for tumor effects; P =.21 for lesion x tumor effect interaction). Survival of mice with SCN lesions was statistically significantly shorter compared with that of sham-operated mice (log-rank P =.0062).Disruption of circadian rhythms in mice was associated with accelerated growth of malignant tumors of two types, suggesting that the host circadian clock may play an important role in endogenous control of tumor progression.
Effect of proinflammatory interleukins on jejunal nutrient transport
Authors: J Hardin
Journal: Gut (2000)

<h3>AIM</h3> We examined the effect of proinflammatory and anti-inflammatory interleukins on jejunal nutrient transport and expression of the sodium-glucose linked cotransporter (SGLT-1). <h3>METHODS</h3> 3-<i>O</i>-methyl glucose and l-proline transport rates were examined in New Zealand White rabbit stripped, short circuited jejunal tissue. The effects of the proinflammatory cytokines interleukin (IL)-1α, IL-6, and IL-8, IL-1α plus the specific IL-1 antagonist, IL-1ra, and the anti-inflammatory cytokine IL-10 were investigated. In separate experiments, passive tissue permeability was assessed and brush border SGLT-1 expression was measured by western blot in tissues exposed to proinflammatory interleukins. <h3>RESULTS</h3> The proinflammatory interleukins IL-6, IL-1α, and IL-8 significantly increased glucose absorption compared with control levels. This increase in glucose absorption was due to an increase in mucosal to serosal flux. IL-1α and IL-8 also significantly increasedl-proline absorption due to an increase in absorptive flux. The anti-inflammatory IL-10 had no effect on glucose transport. The receptor antagonist IL-1ra blocked the ability of IL-1α to stimulate glucose transport. IL-8 had no effect on passive tissue permeability. SGLT-1 content did not differ in brush border membrane vesicles (BBMV) from control or interleukin treated tissue. <h3>CONCLUSIONS</h3> These findings suggest that intestinal inflammation and release of inflammatory mediators such as interleukins increase nutrient absorption in the gut. The increase in glucose transport does not appear to be due to changes in BBMV SGLT-1 content.
Blind Comparative Trial of Fluperolone.
Authors: W. W. Heseltine
Journal: British Journal of Dermatology (1963)

Journal Article Blind Comparative Trial of Fluperolone. Get access W. W. Heseltine W. W. Heseltine E. R. Squibb & Sons, London, W.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 10, 1 October 1963, Page 411, https://doi.org/10.1111/j.1365-2133.1963.tb13925.x Published: 01 October 1963
Salmeterol in paediatric asthma
Authors: C. Byrnes
Journal: Thorax (2000)

<h3>BACKGROUND</h3> The addition of long acting inhaled β<sub>2</sub> agonists is recommended at step 3 of the British guidelines on asthma management but a recent study suggested no additional benefit in children with asthma. <h3>METHODS</h3> The aim of this study was to compare, in a double blind, three way, crossover study, the effects of the addition of salmeterol 50 μg bd, salmeterol 100 μg bd, and salbutamol 200 μg qds in asthmatic children who were symptomatic despite treatment with inhaled corticosteroids in a dose of at least 400 μg/day over a one month period. Symptom scores, morning and evening peak expiratory flow (PEF) rates, use of rescue medication, spirometric indices, and histamine challenge were measured. <h3>RESULTS</h3> Forty five children aged 5–14 years were enrolled. All three treatments improved asthma control, morning and evening PEF rates, and spirometric indices with no change in bronchial hyperreactivity. Mean morning PEF was significantly better during the salmeterol treatment periods than with salbutamol treatment (p&lt;0.05). The analysis of mean morning PEF gave an estimated treatment difference of 9.6 l/min for salmeterol 50 μg bd versus salbutamol 200 μg qds (95% confidence interval (CI) 2.1 to 17.1), and an estimated treatment difference of 13.8 l/min for salmeterol 100 μg bd versus salbutamol 200 μg qds (95% CI 6.0 to 21.5). There were no significant differences between the two doses of salmeterol and all treatments were well tolerated. <h3>CONCLUSIONS</h3> In this population of moderate to severe asthmatic children on inhaled corticosteroids, salmeterol in a dose of either 50 μg bd or 100 μg bd is significantly more effective at increasing the morning PEF rate over a one month period than salbutamol 200 μg qds. The data provided no significant evidence of a difference in efficacy between the two doses of salmeterol, 50 μg and 100 μg. A trial of salmeterol 100 μg bd may be worth considering in those still symptomatic on the lower dose.
Voltage-Dependent Calcium Channel Promoter Restores Baroreflex Sensitivity in Conscious Dogs With Heart Failure
Authors: Masami Uechi, Kuniya Asai, Naoki Sato, Stephen F. Vatner
Journal: Circulation (1998)

Background —The aim of this study was to determine the mechanism by which the calcium channel promoter BAY y 5959 affects the control of heart rate and baroreflex sensitivity in conscious dogs with pacing-induced heart failure (HF). Methods and Results —We compared responses to BAY y 5959, which increases inotropy and decreases chronotropy, with those to norepinephrine (NE), which coincidentally exerts the same directional effects on inotropy and chronotropy, albeit through different mechanisms, in the presence and absence of ganglionic blockade both in control and in HF. Both BAY y 5959 and NE elicit direct effects on the heart and indirect effects through activation of reflexes, primarily the sinoaortic baroreceptor reflex. BAY y 5959 still reduced heart rate in dogs with arterial baroreceptor denervation, but not after ganglionic blockade. HF induced classic catecholamine desensitization to the inotropic effects of NE and blunted reflex bradycardia. In contrast, inotropic responses to BAY y 5959 were preserved in HF. Surprisingly, the autonomically mediated bradycardia induced by BAY y 5959 was also preserved in HF. Baroreflex sensitivity was assessed in control and in HF by pulse interval–systolic arterial blood pressure (PI/SAP) slopes constructed in response to pharmacological alterations in arterial pressure. HF depressed the PI/SAP slope from 11.5±1.3 to 4.8±0.9 ms/mm Hg, but during BAY y 5959 infusion in HF, the PI/SAP slope was restored to 24.1±5.2 ms/mm Hg. To assess central versus peripheral actions of BAY y 5959, the agent was infused with intra–carotid artery perfusion at a low dose, which acted centrally but did not have an effect peripherally. Under these conditions, it still decreased heart rate and restored baroreflex sensitivity (PI/SAP slope, 12.7±2.8 ms/mm Hg). Conclusions —Thus, the calcium promoter restores arterial baroreflex sensitivity in HF. Based on intra–carotid artery experiments, this occurs through a central nervous system and vagal mechanism.
The first case of acinic cell carcinoma of the breast within a fibroadenoma: Case report
Authors: G. Limite, R. Di Micco, E. Esposito, V. Sollazzo, M. Cervotti, G. Pettinato, V. Varone, G. Benassai, A. Monda, G. Luglio, V. Maisto, G. Izzo, P. Forestieri
Journal: International Journal of Surgery (2014)