tbuckley/cabot-search huggingface dataset:
Ranitidine, diarrhoea, and lymphocytic colitis.
Authors: L Beaugerie, N Patey, N Brousse
Journal: Gut (1995)

A 69 year old woman developed chronic diarrhoea while being treated with ranitidine. Sigmoidoscopy was performed after six weeks and showed typical histological features of lymphocytic colitis. Ranitidine was withdrawn and the diarrhoea resolved. Eight months later, a 72 hour oral rechallenge period of ranitidine, was performed immediately preceded (period 1) and followed (period 2) by sigmoidoscopy and biopsy. Diarrhoea recurred during the rechallenge period and resolved again within one day after drug withdrawal. The mean (SEM) intraepithelial lymphocyte count was not significantly different between periods 1 and 2 (11.9 (0.6) and 13.1 (0.4) per 100, respectively). An immunopathological study of 30 serial sections of biopsy specimens was performed for both periods 1 and 2. The expression of HLA-DR by the rectal epithelium was mild or absent in all sections from period 1, and was considerable in 25 of 30 sections from period 2 (p &lt; 10(-9)). It is suggested that the oral intake of ranitidine was responsible for the diarrhoea and induced the immunopathological signs of activation of the rectal mucosal immune system during the rechallenge period.
Antigen-independent Induction of Histamine Synthesis by Immunoglobulin E in Mouse Bone Marrow–derived Mast Cells
Authors: Satoshi Tanaka, Yuhji Takasu, Sonoko Mikura, Norio Satoh, Atsushi Ichikawa
Journal: The Journal of Experimental Medicine (2002)

Immunoglobulin (Ig)E-mediated activation of mast cells has long been thought to occur only when FcϵRI receptor-bound IgE is cross-linked via multivalent antigens. However, recent studies have raised the possibility that mast cells may be activated by the binding of IgE to the FcϵRI receptor in the absence of antigen. Here we demonstrate that IgE binding without antigen induces the expression of histidine decarboxylase (HDC) in mouse interleukin (IL)-3–dependent bone marrow–derived mast cells (BMMCs). The induction of HDC by the binding of IgE was found to require an influx of extracellular calcium ions, which was attenuated by pretreatment with U73122, a phospholipase C inhibitor. Furthermore, the increase in HDC activity upon sensitization with IgE was completely suppressed by pretreatment of BMMCs with protein kinase C inhibitors, such as H7, staurosporine, and Gö6976. In addition, immediate activation of the tyrosine kinase Lyn was not detectable upon treatment with IgE. These results suggest that the binding of IgE to its receptor in the absence of antigen results in de novo synthesis of HDC in BMMCs through a signaling pathway distinct to that operating during antigen-stimulated FcϵRI activation.
Malignant Glioma Cells Counteract Antitumor Immune Responses through Expression of Lectin-Like Transcript-1
Authors: Patrick Roth, Michel Mittelbronn, Wolfgang Wick, Richard Meyermann, Marcos Tatagiba, Michael Weller
Journal: Cancer Research (2007)

Abstract Glioblastoma, one of the most lethal tumors, is paradigmatic for tumor-associated immunosuppression. Lectin-like transcript-1 (LLT1) is a newly identified ligand for the inhibitory natural killer (NK) cell receptor CD161. Here, we report that glioma cells express LLT1 mRNA and protein in vitro and in vivo, whereas expression levels in normal brain are low. LLT1 expression in human gliomas increases with the WHO grade of malignancy. We further show that transforming growth factor-β (TGF-β) up-regulates the expression of LLT1 in glioma cells. Small interfering RNA (siRNA)–mediated down-regulation of LLT1 in LNT-229 and LN-428 cells promotes their lysis by NK cells. Thus, LLT1 acts as a mediator of immune escape and contributes to the immunosuppressive properties of glioma cells. [Cancer Res 2007;67(8):3540–4]
Hyperaldosteronemia in Rabbits Inhibits the Cardiac Sarcolemmal Na <sup>+</sup> -K <sup>+</sup> Pump
Authors: Anastasia S. Mihailidou, Henning Bundgaard, Mahidi Mardini, Peter S. Hansen, Keld Kjeldsen, Helge H. Rasmussen
Journal: Circulation Research (2000)

Aldosterone upregulates the Na(+)-K(+) pump in kidney and colon, classical target organs for the hormone. An effect on pump function in the heart is not firmly established. Because the myocardium contains mineralocorticoid receptors, we examined whether aldosterone has an effect on Na(+)-K(+) pump function in cardiac myocytes. Myocytes were isolated from rabbits given aldosterone via osmotic minipumps and from controls. Electrogenic Na(+)-K(+) pump current, arising from the 3:2 Na(+):K(+) exchange ratio, was measured in single myocytes using the whole-cell patch clamp technique. Treatment with aldosterone induced a decrease in pump current measured when myocytes were dialyzed with patch pipette solution containing Na(+) in a concentration of 10 mmol/L, whereas there was no effect measured when the solution contained 80 mmol/L Na(+). Aldosterone had no effect on myocardial Na(+)-K(+) pump concentration evaluated by vanadate-facilitated [(3)H]ouabain binding or by K(+)-dependent paranitrophenylphosphatase activity in crude homogenates. Aldosterone induced an increase in intracellular Na(+) activity. The aldosterone-induced decrease in pump current and increased intracellular Na(+) were prevented by cotreatment with the mineralocorticoid receptor antagonist spironolactone. Our results indicate that hyperaldosteronemia decreases the apparent Na(+) affinity of the Na(+)-K(+) pump, whereas it has no effect on maximal pump capacity.
Reservoirs for HIV-1: Mechanisms for Viral Persistence in the Presence of Antiviral Immune Responses and Antiretroviral Therapy
Authors: Theodore Pierson, Justin McArthur, Robert F. Siliciano
Journal: Annual Review of Immunology (2000)

The success of combination antiretroviral therapy for HIV-1 infection has generated interest in mechanisms by which the virus can persist in the body despite the presence of drugs that effectively inhibit key steps in the virus life cycle. It is becoming clear that viral reservoirs established early in the infection not only prevent sterilizing immunity but also represent a major obstacle to curing the infection with the potent antiretroviral drugs currently in use. Mechanisms of viral persistence are best considered in the context of the dynamics of viral replication in vivo. Virus production in infected individuals is largely the result of a dynamic process involving continuous rounds of de novo infection of and replication in activated CD4 + T cells with rapid turnover of both free virus and virus-producing cells. This process is largely, but not completely, interrupted by effective antiretroviral therapy. After a few months of therapy, plasma virus levels become undetectable in many patients. Analysis of viral decay rates initially suggested that eradication of the infection might be possible. However, there are several potential cellular and anatomical reservoirs for HIV-1 that may contribute to long-term persistence of HIV-1. These include infected cell in the central nervous system and the male urogenital tract. However, the most worrisome reservoir consists of latently infected resting memory CD4 + T cells carrying integrated HIV-1 DNA. Definitive demonstration of the presence of this form of latency required development of methods for isolating extremely pure populations of resting CD4 + T cells and for demonstrating that a small fraction of these cells contain integrated HIV-1 DNA that is competent for replication if the cells undergo antigen-driven activation. Most of the latent virus in resting CD4 + T cells is found in cells of the memory phenotype. The half-life of this latent reservoir is extremely long (44 months). At this rate, eradication of this reservoir would require over 60 years of treatment. Thus, latently infected resting CD4 + T cells provide a mechanism for life-long persistence of replication-competent forms of HIV-1, rendering unrealistic hopes of virus eradication with current antiretroviral regimens. The extraordinary stability of the reservoir may reflect gradual reseeding by a very low level of ongoing viral replication and/or mechanisms that contribute to the intrinsic stability of the memory T cell compartment. Given the substantial long-term toxicities of current combination therapy regimens, novel approaches to eradicating this latent reservoir are urgently needed.
Non-toxic phototriggered gene transfection by PAMAM-porphyrin conjugates
Authors: Ming-Jium Shieh, Cheng-Liang Peng, Pei-Jen Lou, Chieh-Hua Chiu, Tsiao-Yu Tsai, Chia-Yen Hsu, Chen-Yu Yeh, Ping-Shan Lai
Journal: Journal of Controlled Release (2008)
A 1-Year Lifestyle Intervention for Weight Loss in Individuals With Type 2 Diabetes Reduces High C-Reactive Protein Levels and Identifies Metabolic Predictors of Change
Authors: L. Maria Belalcazar, David M. Reboussin, Steven M. Haffner, Ron C. Hoogeveen, Andrea M. Kriska, Dawn C. Schwenke, Russell P. Tracy, F. Xavier Pi-Sunyer, Christie M. Ballantyne
Journal: Diabetes Care (2010)

We examined whether a 1-year intensive lifestyle intervention (ILI) for weight loss reduced elevated high-sensitivity C-reactive protein (hs-CRP) levels in obese individuals with diabetes and identified metabolic and fitness predictors of hs-CRP change.Look AHEAD (Action for Health in Diabetes) is an ongoing multicenter clinical trial examining the effects of weight loss achieved through ILI on cardiovascular events and overall mortality in obese/overweight adults with type 2 diabetes. We report on 1,759 Look AHEAD participants who had hs-CRP and fitness data at baseline and 1 year. Subjects were randomly assigned to ILI or to usual care (diabetes support and education [DSE]). ILI involved frequent counseling to increase moderate-intensity exercise to 175 min/week, reduce caloric and saturated fat intake, and change macronutrient composition to improve glycemic control.ILI reduced median hs-CRP by 43.6% from baseline to 1 year, compared with a 16.7% reduction with DSE (P<0.001). ILI decreased weight (8.8%), A1C (0.7%), and triglycerides (17%) and increased fitness (19%) and HDL cholesterol (7.5%) (P<0.0001 vs. changes with DSE). Changes in adiposity and glucose control with ILI remained independent predictors of hs-CRP change at 1 year (P<0.0001 for each) after adjustment for demographics, smoking, cardiovascular history, statin and thiazolidinedione use, and changes in fitness and lipid control. Neither statin nor insulin therapy modified the association between ILI and hs-CRP.A 1-year lifestyle intervention for weight loss in obese individuals with diabetes was associated with substantial reductions in hs-CRP. Improved glycemic control and reduced adiposity had comparable effects on hs-CRP change.
Cancer DNA Methylation: Molecular Mechanisms and Clinical Implications
Authors: Michael T. McCabe, Johann C. Brandes, Paula M. Vertino
Journal: Clinical Cancer Research (2009)

DNA methylation plays a crucial role in the regulation of gene expression and chromatin organization within normal eukaryotic cells. In cancer, however, global patterns of DNA methylation are altered with global hypomethylation of repeat-rich intergenic regions and hypermethylation of a subset of CpG-dense gene-associated regions (CpG islands). Extensive research has revealed the cellular machinery that catalyzes DNA methylation, as well as several large protein complexes that mediate the transcriptional repression of hypermethylated genes. However, research is only just beginning to uncover the molecular mechanisms underlying the origins of cancer-specific DNA methylation. Herein, we present several recent advances regarding these mechanisms and discuss the relationship between histone modifications (i.e., H3K4me2/3, H4K16Ac, H3K9me2/3, H3K27me3, H4K20me3), chromatin-modifying enzymes (G9a, EZH2, hMOF, SUV4-20H), and aberrant DNA methylation. Additionally, the role played by inflammation, DNA damage, and miRNAs in the etiology of aberrant DNA methylation is considered. Finally, we discuss the clinical implications of aberrant DNA methylation and the utility of methylated biomarkers in cancer diagnosis and management.
Pseudotumor cerebri in children receiving recombinant human growth hormone
Authors: Adam H Rogers, Gary L Rogers, Don L Bremer, Mary Lou McGregor
Journal: Ophthalmology (1999)

PurposeThis article represents the first report in the ophthalmology literature of an association between pseudotumor cerebri (PTC) and recombinant human growth hormone (rhGH).DesignNoncomparative case series.ParticipantsThree children receiving rhGH for short stature with Turner syndrome, Jeune syndrome, or Down syndrome.MethodsChildren underwent full ocular examination. After papilledema was identified, patients underwent lumbar puncture and imaging with either magnetic resonance imaging or computerized tomography. Treatment was under the guidance of the primary physician or neurosurgeon. The rhGH was discontinued in all children.Main outcome measuresVisual acuity and evaluation of the optic nerve for resolution of papilledema were followed at each examination.ResultsIn all three cases, papilledema resolved with the cessation of rhGH, and treatment with acetazolamide or prednisone. Visual acuity was unchanged in case 1, decreased by two to three lines in case 2, and was inconsistent in case 3. One child (case 2) required a ventriculoperitoneal shunt for persistent elevation of intracranial pressure.ConclusionThere appears to be a causal relationship between the initiation of rhGH with the development of PTC. Children should have a complete ophthalmic evaluation if they report headache or visual disturbances. Baseline examination with routine follow-up should be instituted when children cannot adequately communicate.
Long-term budesonide treatment of collagenous colitis: a randomised, double-blind, placebo-controlled trial
Authors: O K Bonderup, J B Hansen, P S Teglbjaerg, L A Christensen, J F Fallingborg
Journal: Gut (2008)

To evaluate the efficacy and safety of long-term budesonide therapy for the maintenance of clinical remission in patients with collagenous colitis.Randomised, placebo-controlled study with a 24-week, blinded follow-up period without any treatment.Three gastroenterology clinics in Denmark.Forty-two patients with histologically confirmed collagenous colitis and diarrhoea (more than three stools/day).Patients in clinical remission after 6 weeks' open-label therapy with oral budesonide (Entocort CIR capsules, 9 mg/day) received 24 weeks' double-blind maintenance therapy with budesonide 6 mg/day or placebo. Thereafter, patients entered the 24-week, blinded follow-up period.The proportion of patients in clinical remission (three or fewer stools/day) at the end of maintenance therapy.A total of 34 patients in remission at week 6 were randomly assigned to budesonide 6 mg/day (n = 17) or placebo (n = 17). After 24 weeks' maintenance treatment, the proportions of patients in clinical remission were 76.5% (13 of 17) with budesonide and 12% (2 of 17) with placebo (p<0.001). At 48 weeks (the end of the follow-up period, without any treatment) these values were 23.5% (4 of 17) and 12% (2 of 17), respectively (p = 0.6). The median times to relapse after stopping active treatment (6 plus 24 weeks in the budesonide group; 6 weeks in the placebo group) were 39 and 38 days, respectively. Long-term treatment with budesonide was well tolerated.Long-term maintenance therapy with oral budesonide is efficacious and well tolerated for preventing relapse in patients with collagenous colitis. The risk of relapse after 24 weeks' maintenance treatment is similar to that observed after 6 weeks' induction therapy.
Simultaneous Inhibition of EGFR, VEGFR, and Platelet-Derived Growth Factor Receptor Signaling Combined with Gemcitabine Produces Therapy of Human Pancreatic Carcinoma and Prolongs Survival in an Orthotopic Nude Mouse Model
Authors: Kenji Yokoi, Takamitsu Sasaki, Corazon D. Bucana, Dominic Fan, Cheryl H. Baker, Yasuhiko Kitadai, Toshio Kuwai, James L. Abbruzzese, Isaiah J. Fidler
Journal: Cancer Research (2005)

Abstract Although gemcitabine has been approved as the first-line chemotherapeutic reagent for pancreatic cancer, its response rate is low and average survival duration is still only marginal. Because epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR) modulate tumor progression, we hypothesized that inhibition of phosphorylation of all three on tumor cells, tumor-associated endothelial cells, and stroma cells would improve the treatment efficacy of gemcitabine in an orthotopic pancreatic tumor model in nude mice and prolong survival. We implanted L3.6pl, a human pancreatic cancer cell, in the pancreas of nude mice. We found that tumor-associated endothelial cells in this model highly expressed phosphorylated EGFR, VEGFR, and PDGFR. Oral administration of AEE788, a dual tyrosine kinase inhibitor against EGFR and VEGFR, decreased phosphorylation of EGFR and VEGFR. PDGFR phosphorylation was inhibited by STI571. Although i.p. injection of gemcitabine did not inhibit tumor growth, its combination with AEE788 and STI571 produced &amp;gt;80% inhibition of tumor growth and prolonged survival in parallel with increases in number of tumor cells and tumor-associated endothelial cell apoptosis, decreased microvascular density, decreased proliferation rate, and prolonged survival. STI571 treatment also decreased pericyte coverage on tumor-associated endothelial cells. Thus, inhibiting phosphorylation of EGFR, VEGFR, and PDGFR in combination with gemcitabine enhanced the efficacy of gemcitabine, resulting in inhibition of experimental human pancreatic cancer growth and significant prolongation of survival.
Temporal Dynamics of Brain Anatomy
Authors: Arthur W. Toga, Paul M. Thompson
Journal: Annual Review of Biomedical Engineering (2003)

▪ Abstract The brain changes profoundly in structure and function during development and as a result of diseases such as the dementias, schizophrenia, multiple sclerosis, and tumor growth. Strategies to measure, map, and visualize these brain changes are of immense value in basic and clinical neuroscience. Algorithms that map brain change with sufficient spatial and temporal sensitivity can also assess drugs that aim to decelerate or arrest these changes. In neuroscience studies, these tools can reveal subtle brain changes in adolescence and old age and link these changes with measurable differences in brain function and cognition. Early detection of brain change in patients at risk for dementia; tumor recurrence; or relapsing-remitting conditions, such as multiple sclerosis, is also vital for optimizing therapy. We review a variety of mathematical and computational approaches to detect structural brain change with unprecedented sensitivity, both spatially and temporally. The resulting four-dimensional (4-D) maps of brain anatomy are warehoused in population-based brain atlases. Here, statistical tools compare brain changes across subjects and across populations, adjusting for complex differences in brain structure. Brain changes in an individual can be compared with a normative database comprised of subjects matched for age, gender, and other demographic factors. These dynamic brain maps offer key biological markers for understanding disease progression and testing therapeutic response. The early detection of disease-related brain changes is also critical for possible pre-emptive intervention before the ravages of disease have set in.
State of Diabetes, Hypertension, and Comorbidity in Kuwait: Showcasing the Trends as Seen in Native Versus Expatriate Populations
Authors: Arshad Mohamed Channanath, Bassam Farran, Kazem Behbehani, Thangavel Alphonse Thanaraj
Journal: Diabetes Care (2013)

The global epidemic of diabetes and related disorders has not spared the states of Gulf Cooperation Council, particularly Kuwait (1,2). Socioeconomic changes in the post-oil era have promoted a sedentary lifestyle and an intake of high-calorie food. Expatriates, who form the workforce, constitute two-thirds of the Kuwait population; migrants are at greater risk of developing diabetes (3). We undertook a retrospective cohort study using nationwide data from the Kuwait Health Network, which integrates records from primary health clinics and hospitals. The dataset, after quality control, includes 270,172 participants comprising natives and expatriates.

Crude prevalence of type 1 diabetes is 2.8% among expatriates and 2.3% among natives (age-group 0–20 years). Asian expatriates (age-group 30–60 years) exhibit higher prevalence of type 2 diabetes (and hypertension) at 33.25% (and 37%) than natives at 25.4% (and 28%). Prevalence of coexistence of diabetes and hypertension is 11%, irrespective of ethnicities. Prevalence increases with advancing …
Phase III Comparison of Vitespen, an Autologous Tumor-Derived Heat Shock Protein gp96 Peptide Complex Vaccine, With Physician's Choice of Treatment for Stage IV Melanoma: The C-100-21 Study Group
Authors: Alessandro Testori, Jon Richards, Eric Whitman, G. Bruce Mann, Jose Lutzky, Luis Camacho, Giorgio Parmiani, Giulio Tosti, John M. Kirkwood, Axel Hoos, Lianng Yuh, Renu Gupta, Pramod K. Srivastava
Journal: Journal of Clinical Oncology (2008)

To assess the antitumor activity of vitespen (autologous, tumor- derived heat shock protein gp96 peptide complexes) by determining whether patients with stage IV melanoma treated with vitespen experienced longer overall survival than patients treated with physician's choice.Patients (N = 322) were randomly assigned 2:1 to receive vitespen or physician's choice (PC) of a treatment containing one or more of the following: dacarbazine, temozolomide, interleukin-2, or complete tumor resection. This open-label trial was conducted at 71 centers worldwide. Patients were monitored for safety and overall survival.Therapy with vitespen is devoid of significant toxicity. Patients randomly assigned to the vitespen arm received variable number of injections (range, 0 to 87; median, 6) in part because of the autologous nature of vitespen therapy. Intention-to-treat analysis showed that overall survival in the vitespen arm is statistically indistinguishable from that in the PC arm. Exploratory landmark analyses show that patients in the M1a and M1b substages receiving a larger number of vitespen immunizations survived longer than those receiving fewer such treatments. Such difference was not detected for substage M1c patients.These results are consistent with the immunologic mechanism of action of vitespen, indicating delayed onset of clinical activity after exposure to the vaccine. The results suggest patients with M1a and M1b disease who are able to receive 10 or more doses of vitespen as the candidate population for a confirmatory study.
Medical science: Master or servant?
Authors: R. V. Facey
Journal: BMJ (1967)

BRITISBThe observation that the fasting serum folate activity remained low does not disprove that the haematological response was the result of folate in the diet after admission, as it is possible to treat megaloblastic anaemia without replenishing body folate stores.3Any relationship between folate metabolism and ascorbic acid remains obscure, but it has been shown that patients with only slight evidence of folate deficiency may become frankly megaloblastic when treated with ascorbic acid alone and a folic acid-free diet.4 5 The contradictory reports of ascorbic acid converting megaloblastic erythropoiesis to normoblastic and normoblastic erythro- poiesis to megaloblastic are probably explained by the former studies not being conducted on folate-free diets, and by an increased utiliza- tion and low intake of folate in the latter.As a patient who has scurvy is likely to be folate-deficient, it seems sensible to give folic acid to all scorbutic patients and also to ensure that they are not deficient of vitamin B12 and iron.-Weare, etc.,