tbuckley/cabot-search huggingface dataset:
Evidence for a Role for Insulin and Growth Hormone in Overnight Regulation of 3-Hydroxybutyrate in Normal and Diabetic Adolescents
Authors: Julie A Edge, Dorothy A Harris, Paula E Phillips, B Rani Pal, David R Matthews, David B Dunger
Journal: Diabetes Care (1993)

Objective— To determine the relative effects of growth hormone and insulin on ketogenesis during puberty. Research Design and Methods— We studied overnight changes in plasma ketones—3-hydroxybutyrate and acetoacetate—in 35 normal and 26 IDDM adolescents at different stages of puberty. The diabetic adolescents either were on their normal insulin regimen or were studied during an overnight euglycemic clamp with or without suppression of endogenous growth hormone release. Results— Total ketone body and 3-hydroxybutyrate concentrations in the normal adolescents rose significantly from 2000 (29 ± 5 μM), reaching a peak at 0200 (103 ± 16 μM, P &amp;lt; 0.001 vs. 2000). After a brief fall, a further rise occurred before breakfast. Fasting 3-hydroxybutyrate concentrations showed a negative correlation with fasting insulin levels (r = −0.46, P = 0.005) and decreased with advancing puberty, while insulin concentrations increased. In the diabetic patients on their usual insulin regimen, free insulin levels waned overnight, and an exaggerated rise in ketones was observed before breakfast. During the euglycemic clamp studies, ketone levels were higher than normal throughout the night. Mean overnight growth hormone and free insulin levels also were higher than in the normal control subjects. The addition of the anticholinergic drug pirenzepine reduced growth hormone secretion and obliterated the early-night peak of 3-hydroxybutyrate. Conclusions— We conclude that the early-night peak of ketone concentrations is related to growth hormone release, whereas the fasting levels are largely determined by insulin concentration. Inadequate insulin delivery in the presence of the high growth hormone concentrations characteristic of diabetic adolescents could lead to rapid decompensation and ketoacidosis.
Phase I/II Trial of Erlotinib and Cisplatin in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: A Princess Margaret Hospital Phase II Consortium and National Cancer Institute of Canada Clinical Trials Group Study
Authors: Lillian L. Siu, Denis Soulieres, Eric X. Chen, Gregory R. Pond, Soo F. Chin, Peggy Francis, Luc Harvey, Meri Klein, Wenjiang Zhang, Janet Dancey, Elizabeth A. Eisenhauer, Eric Winquist
Journal: Journal of Clinical Oncology (2007)

To determine the phase II dose and objective response rate of erlotinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC).HNSCC patients with no prior chemotherapy and measurable disease were treated in three escalating-dose cohorts of daily continuous oral (PO) erlotinib and intermittent intravenous (IV) cisplatin given every 21 days. The recommended phase II dose (RPTD) was then evaluated in a two-stage trial with a primary end point of objective response rate.A total of 51 patients were enrolled. The RPTD was identified as erlotinib 100 mg PO daily and cisplatin 75 mg/m2 IV every 21 days. Forty-five patients were treated at the RPTD, of which 44 and 43 were eligible for toxicity and efficacy evaluations, respectively. The intention-to-treat response rate was 21%, with one complete and eight partial responses (95% CI, 10% to 36%), and disease stabilization was achieved in 21 patients (49%; 95% CI, 33% to 65%). Median progression-free survival was 3.3 months (95% CI, 2.7 to 4.8 months) and median overall survival was 7.9 (95% CI, 5.6 to 9.5) months. The combination was well tolerated, with minimal grade 3 or higher toxicity. Subgroup analysis suggested that patients who developed higher grade skin rashes during cycle 1 had better survival outcomes (P = .034).This schedule of erlotinib and cisplatin has a favorable toxicity profile and has antitumor activity in HNSCC comparable to standard combination chemotherapy regimens.
<i>In vitro</i>and<i>In vivo</i>Characterization of MDX-1401 for Therapy of Malignant Lymphoma
Authors: Pina M. Cardarelli, Maria-Cristina Moldovan-Loomis, Ben Preston, Amelia Black, David Passmore, Tseng-Hui Chen, Sharline Chen, Jie Liu, Michelle R. Kuhne, Mohan Srinivasan, Albert Assad, Alison Witte, Robert F. Graziano, David J. King
Journal: Clinical Cancer Research (2009)

This study was undertaken to evaluate the effects of MDX-1401, a nonfucosylated fully human monoclonal antibody that binds to human CD30, and to determine whether it exhibits greater in vitro and in vivo activity than its parental antibody.Assays measuring antibody binding to CD30-expressing cells and FcgammaRIIIa (CD16) transfectants as well as antibody-dependent cellular cytotoxicity (ADCC) were conducted. Antitumor activity was determined using a Karpas-299 systemic model.The binding of MDX-1401 to CD30 antigen was identical to fucose-containing parental anti-CD30 antibody (MDX-060). In contrast, MDX-1401 showed increased binding affinity to FcgammaRIIIa-transfected cells resulting in increased effector function. MDX-1401 greatly improved ADCC activity as evidenced by a decrease in half-maximal effective concentration (EC(50)) and an increase in maximum cell lysis when compared with MDX-060. Increased ADCC activity was observed among a panel of cell lines, including one with very low CD30 antigen expression in which parental antibody failed to induce any detectable ADCC. MDX-1401 activity with all FcgammaRIIIa polymorphic variants, including less active Phe/Phe158 and Phe/Val158 effector cells, was shown. Furthermore, MDX-1401 was efficacious in inhibiting tumor growth in CD30(+) lymphoma xenografts.The low doses of antibody required for ADCC activity irrespective of donor genotype, the ability to mediate ADCC in target cells expressing low levels of CD30, and increased in vivo efficacy support the development of MDX-1401 for treatment of malignant lymphoma.
Immune Stimulated Regional Inflammatory Responses Mediating Lung Reactivity in Rats
Authors: S. Ahlstedt, B. Bjøurkstéan, B. Hesselmar, H. Nygren, K. Alving, E. Olaisson
Journal: Allergy (1985)

Daily sensitization of SPF BNxWi/Fu rats with ovalbumin (OA) in aerosol during 2-week periods with a 4-week interval resulted after 7 weeks in IgE, IgA and IgG antibodies in serum and bronchial fluid. After cultivation of the regional, axillary, brachial and mediastinal (ABM) lymph node cells, IgE antibodies were found in the culture supernatant. Such antibodies were not found in culture supernatants of spleen and inguinal lymph nodes. Regional formation of IgE antibodies was also noted in the ABM lymph node cell culture supernatants after subcutaneous (s.c.) injections of 100 ng OA in the neck region. When the injections were given in the tail-root region, the inguinal but not the ABM lymph nodes produced the IgE antibodies. The s.c. sensitization induced inconsistent and rather low IgG and no IgA antibody responses. The aerosol but not the s.c. sensitization induced accumulations of mononuclear cells and mucous cells in the lungs. Clinically, the rats sensitized s.c. in the neck region reacted to aerosol and intravenous (i.v.) challenge as early as 1 week after sensitization had started, whereas the animals sensitized in the tail-root regions reacted 7 and 8 weeks after repeated sensitization. The animals sensitized by aerosol showed only weak clinical reactivity after i.v. challenge.
Harnessing naturally randomized transcription to infer regulatory relationships among genes
Authors: Lin S Chen, Frank Emmert-Streib, John D Storey
Journal: Genome biology (2007)

Abstract We develop an approach utilizing randomized genotypes to rigorously infer causal regulatory relationships among genes at the transcriptional level, based on experiments in which genotyping and expression profiling are performed. This approach can be used to build transcriptional regulatory networks and to identify putative regulators of genes. We apply the method to an experiment in yeast, in which genes known to be in the same processes and functions are recovered in the resulting transcriptional regulatory network.
Proximal tubule volume regulation in hypo-osmotic media
Authors: L Rome, C Lechene, J J Grantham
Journal: Journal of the American Society of Nephrology (1990)

This study sought to measure the net loss of intracellular K+, Na+, and Cl- that accompanied isosmotic cell volume regulation in hypotonic media and to determine if electrolyte loss depended on the rate at which the extracellular osmolality was reduced. Isolated nonperfused proximal S2 segments from rabbit kidney cortex were studied in vitro. Gradual lowering of osmolality from 295 to 150 mOsm/kg at a rate of 2 mOsm/kg/min did not cause an increase in tubule cell volume until the medium osmolality decreased below 190 mOsm/kg. By contrast, tubules rapidly bathed in low osmolality media exhibited classical osmometric swelling followed by incomplete volume regulatory decrease. Volume regulation associated with gradual and rapid lowering of osmolality was accompanied by the net loss of intracellular K+, Na+, and Cl- (measured by electron probe); however, the temporal pattern of electrolyte loss depended on the rate of osmotic change. With gradual lowering of osmolality, cell K+ content did not decrease significantly until osmolality was lowered below 200 mOsm/kg, whereas Cl- was lost at the 200 mOsm/kg level and below. With rapid lowering of osmolality, cell K+ content was strikingly decreased at the 200 mOsm/kg level, but Cl- did not change appreciably until osmolality was decreased to 150 mOsm/kg. Cell Na+ content decreased in hypo-osmotic media, but the magnitude was relatively small. During volume regulation that accompanied either gradual or rapid lowering of medium osmolality from 295 to 150 mOsm/kg, intracellular osmolal gap, the difference between medium osmolality and the sum of intracellular concentrations of K+, Na+, and Cl- decreased 87 and 58 mOsm/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease
Authors: Hiroyuki Kobori, Masaomi Nangaku, L. Gabriel Navar, Akira Nishiyama
Journal: Pharmacological Reviews (2007)

In recent years, the focus of interest on the role of the renin-angiotensin system (RAS) in the pathophysiology of hypertension and organ injury has changed to a major emphasis on the role of the local RAS in specific tissues. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by independent multiple mechanisms. Proximal tubular angiotensinogen, collecting duct renin, and tubular angiotensin II type 1 (AT1) receptors are positively augmented by intrarenal Ang II. In addition to the classic RAS pathways, prorenin receptors and chymase are also involved in local Ang II formation in the kidney. Moreover, circulating Ang II is actively internalized into proximal tubular cells by AT1 receptor-dependent mechanisms. Consequently, Ang II is compartmentalized in the renal interstitial fluid and the proximal tubular compartments with much higher concentrations than those existing in the circulation. Recent evidence has also revealed that inappropriate activation of the intrarenal RAS is an important contributor to the pathogenesis of hypertension and renal injury. Thus, it is necessary to understand the mechanisms responsible for independent regulation of the intrarenal RAS. In this review, we will briefly summarize our current understanding of independent regulation of the intrarenal RAS and discuss how inappropriate activation of this system contributes to the development and maintenance of hypertension and renal injury. We will also discuss the impact of antihypertensive agents in preventing the progressive increases in the intrarenal RAS during the development of hypertension and renal injury.
Bullous pemphigoid triggered by influenza vaccination? Ecological study in Galicia, Spain
Authors: I. García-Doval, E. Mayo, J. Nogueira Fariña, M.J. Cruces
Journal: British Journal of Dermatology (2006)

Journal Article Bullous pemphigoid triggered by influenza vaccination? Ecological study in Galicia, Spain Get access I. García‐Doval, I. García‐Doval Departments of Dermatology and Medical Documentation, Complexo Hospitalario de Pontevedra, C/Loureiro Crespo 2, Pontevedra E‐36000, Spain Ignacio García‐Doval. E‐mail: igarciad@meditex.es Search for other works by this author on: Oxford Academic Google Scholar E. Mayo, E. Mayo Departments of Dermatology and Medical Documentation, Complexo Hospitalario de Pontevedra, C/Loureiro Crespo 2, Pontevedra E‐36000, Spain Search for other works by this author on: Oxford Academic Google Scholar J. Nogueira Fariña, J. Nogueira Fariña Departments of Dermatology and Medical Documentation, Complexo Hospitalario de Pontevedra, C/Loureiro Crespo 2, Pontevedra E‐36000, Spain Search for other works by this author on: Oxford Academic Google Scholar M.J. Cruces M.J. Cruces Departments of Dermatology and Medical Documentation, Complexo Hospitalario de Pontevedra, C/Loureiro Crespo 2, Pontevedra E‐36000, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 4, 1 October 2006, Pages 820–823, https://doi.org/10.1111/j.1365-2133.2006.07411.x Published: 01 October 2006 Article history Accepted: 24 March 2006 Published: 01 October 2006
Risk assessment after acute upper gastrointestinal haemorrhage.
Authors: T A Rockall, R F Logan, H B Devlin, T C Northfield
Journal: Gut (1996)

The aim of this study was to establish the relative importance of risk factors for mortality after acute upper gastrointestinal haemorrhage, and to formulate a simple numerical scoring system that categorizes patients by risk. A prospective, unselected, multicentre, population based study was undertaken using standardised questionnaires in two phases one year apart. A total of 4185 cases of acute upper gastrointestinal haemorrhage over the age of 16 identified over a four month period in 1993 and 1625 cases identified subsequently over a three month period in 1994 were included in the study. It was found that age, shock, comorbidity, diagnosis, major stigmata of recent haemorrhage, and rebleeding are all independent predictors of mortality when assessed using multiple logistic regression. A numerical score using these parameters has been developed that closely follows the predictions generated by logistical regression equations. Haemoglobin, sex, presentation (other than shock), and drug therapy (non-steroidal anti-inflammatory drugs and anticoagulants) are not represented in the final model. When tested for general applicability in a second population, the scoring system was found to reproducibly predict mortality in each risk category. In conclusion, a simple numerical score can be used to categorize patients presenting with acute upper gastrointestinal haemorrhage by risk of death. This score can be used to determine case mix when comparing outcomes in audit and research and to calculate risk standardised mortality. In addition, this risk score can identify 15% of all cases with acute upper gastrointestinal haemorrhage at the time of presentation and 26% of cases after endoscopy who are at low risk of rebleeding and negligible risk of death and who might therefore be considered for early discharge or outpatient treatment with consequent resource savings.
A history of gallstones associated with increased risk of psoriasis in U.S. women
Authors: Y.-S. Lin
Journal: British Journal of Dermatology (2015)

Journal Article A history of gallstones associated with increased risk of psoriasis in U.S. women Get access Y.‐S. Lin Y.‐S. Lin School of Medicine College of Medicine Chi Mei Medical Center Taipei Medical University 901 Chung Hwa Road Yung Kan District Tainan City Taiwan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 5, 1 May 2015, Pages 1187–1188, https://doi.org/10.1111/bjd.13773 Published: 01 May 2015
Supplementation of N-acetylcysteine as an adjuvant in treatment of newly diagnosed pulmonary tuberculosis patients: A prospective, randomized double blind, placebo controlled study
Authors: Dinesh Nagrale, Sunil Mahakalkar, Sanjay Gaur
Journal: European Respiratory Journal (2013)

BACKGROUND: Pulmonary tuberculosis (PTB) is associated with significant increase in lipid peroxidation and decreased glutathione. It is reported that N-acetylcysteine could be effective in conditions with such oxidative stress.However,there are no clinical studies to show its efficacy in PTB patients.Hence this study.  OBJECTIVE: To investigate if supplementation of N-acetylcysteine (NAC) adjuvant to DOTS-1 regimen reduces the oxidative stress in these patients and has a beneficial treatment outcome.Also to co-relate glutathione levels with correction of immune dysregulation in pulm.tuberculosis and role of glutathione in immunopathogenesis of PTB.  MATERIAL & METHOD: Prospective, randomized, double–blind, placebo controlled study in patients with newly diagnosed sputum positive PTB,divided into 2 groups. Gr.A (n=33) received tablet NAC 600mg while Gr.B (n=34) received placebo, two times a day for 2 months (intensive phase of chemotherapy). Both the study groups received (DOTS category I).48 patients completed study.  RESULTS : NAC significantly caused early sputum negativity (p=0.0019), radiological improvement (p  CONCLUSION: NAC as an adjuvant appears to be an effective agent in terms of early bacteriological and radiological improvement in treatment of pulm.tuberculosis. Its antioxidant and immunological effect are contributory in early clinical cure in these patients.
Clinical Presentations and Treatment Outcomes of Peacekeeper Veterans With PTSD: Preliminary Findings
Authors: David Forbes, Neanne Bennett, Dirk Biddle, David Crompton, Tony McHugh, Peter Elliott, Mark Creamer
Journal: American Journal of Psychiatry (2005)

Despite evidence of potential psychiatric sequelae following peacekeeping operations, no data have appeared on treatment outcome for this population. This study examined intake and treatment outcome data for a group of peacekeepers with posttraumatic stress disorder (PTSD).Participants were 63 Australian Vietnam veterans and 66 Australian peacekeepers attending specialized PTSD treatment units. Measures of PTSD, depression, anxiety, alcohol use, and anger were obtained at intake and 3-month follow-up.PTSD scores were more severe for peacekeepers than Vietnam veterans at intake, primarily in reexperiencing symptoms. In terms of comorbidity, only anger was higher among peacekeepers. No differences were apparent in treatment outcome. Initial anger predicted change in PTSD severity for peacekeepers.The finding of differences between peacekeepers and Vietnam veterans in anger and reexperiencing symptoms, in addition to the attenuating role of anger on treatment outcome, suggests that modification to standard PTSD treatment models may be warranted for peacekeepers.
Potential Changes Attending the Excitation Process in the Atrioventricular Conduction System of Bovine and Canine Hearts
Authors: RAYMOND D. PRUITT, HIRAM E. ESSEX
Journal: Circulation Research (1960)

Potential changes attending excitation of the atrioventricular node, the common bundle, the bundle branches, and initial ramifications of the conducting tissue in the subendocardium of the bovine heart beating in situ have been recorded from unipolar exploring electrodes. Correlations between the form of nodal deflection and the location in the node of the electrode tip have been established. From right bundle branch and subendocardial action potentials, data were derived indicating a rate of transmission through the right branch of 2.02 M/sec. Certain observations on the effects of acute injury and severe hypoxia are recorded. The character of nodal deflections attending retrograde excitation is reviewed. In studies on canine hearts beating in situ , electrograms have been made from the regions in which the atrioventricular node, the common bundle, and bundle branches are believed to lie. Deflections comparable to those recorded in bovine experiments were encountered and, by analogy with those bovine studies, certain morphologic correlations postulated. In general, canine nodal deflections are smaller than their bovine counterparts and lack the variety of form ascribed to potential changes in the several portions of the bovine node. In canine studies, deflections of atrial, atrionodal, and nodal type coexisted in recordings from a single needle electrode suggesting a degree of proximity between the sources of these potential changes not encountered in bovine experiments.
Oral N-acetylcysteine reduces bleomycin-induced collagen deposition in the lungs of mice
Authors: S Shahzeidi, B Sarnstrand, PK Jeffery, RJ McAnulty, GJ Laurent
Journal: European Respiratory Journal (1991)

N-acetylcysteine (NAC) has been employed in the treatment of acute lung injury but its therapeutic value is as yet unproven. In the present study we examined the effect of both L- and D-forms of NAC as inhibitors of bleomycin-induced fibrosis in mice. We hypothesized that, because of the D-form is not metabolized, it may be more effective than the L-form in ameliorating lung injury and fibrosis. Both drugs were given daily in the drinking water at a dose of approximately 400 mg.kg-1 body weight commencing one week prior to a single intratracheal instillation of bleomycin at a dose of 6 mg.kg-1 body weight. Lung injury was assessed 35 days later by measuring total lung collagen content, lung wet weight and examination of tissues by light and electron microscopy. Total collagen content and lung wet weight of animals receiving bleomycin together with L-NAC were 2.90 +/- 0.03 mg and 0.23 +/- 0.01 g, respectively. The values for collagen content, but not wet weight, were significantly less (p less than 0.05) than those given for bleomycin alone (3.90 +/- 0.02 mg and 0.260 +/- 0.005 g, respectively), but greater than (p less than 0.05) controls (2.10 +/- 0.01 mg and 0.160 +/- 0.002 g, respectively). Values for collagen content and wet weight of animals given bleomycin together with D-NAC (3.10 +/- 0.02 mg and 0.21 +/- 0.01 mg, respectively) were both significantly greater than values for control animals but lower than animals given bleomycin alone.(ABSTRACT TRUNCATED AT 250 WORDS)