tbuckley/cabot-search huggingface dataset:
<i>EMP3</i>, a Myelin-Related Gene Located in the Critical 19q13.3 Region, Is Epigenetically Silenced and Exhibits Features of a Candidate Tumor Suppressor in Glioma and Neuroblastoma
Authors: Miguel Alaminos, Verónica Dávalos, Santiago Ropero, Fernando Setién, Maria F. Paz, Michel Herranz, Mario F. Fraga, Jaume Mora, Nai-Kong V. Cheung, William L. Gerald, Manel Esteller
Journal: Cancer Research (2005)

Abstract The presence of common genomic deletions in the 19q13 chromosomal region in neuroblastomas and gliomas strongly suggests the presence of a putative tumor suppressor gene for these neoplasms in this region that, despite much effort, has not yet been identified. In an attempt to address this issue, we compared the expression profile of 89 neuroblastoma tumors with that of benign ganglioneuromas by microarray analysis. Probe sets (637 of 62,839) were significantly down-regulated in neuroblastoma tumors, including, most importantly, a gene located at 19q13.3: the epithelial membrane protein 3 (EMP3), a myelin-related gene involved in cell proliferation and cell-cell interactions. We found that EMP3 undergoes hypermethylation-mediated transcriptional silencing in neuroblastoma and glioma cancer cell lines, whereas the use of the demethylating agent 5-aza-2-deoxycytidine restores EMP3 gene expression. Furthermore, the reintroduction of EMP3 into neuroblastoma cell lines displaying methylation-dependent silencing of EMP3 induces tumor suppressor–like features, such as reduced colony formation density and tumor growth in nude mouse xenograft models. Screening a large collection of human primary neuroblastomas (n = 116) and gliomas (n = 41), we observed that EMP3 CpG island hypermethylation was present in 24% and 39% of these tumor types, respectively. Furthermore, the detection of EMP3 hypermethylation in neuroblastoma could be clinically relevant because it was associated with poor survival after the first 2 years of onset of the disease (Kaplan-Meier; P = 0.03) and death of disease (Kendall τ, P = 0.03; r = 0.19). Thus, EMP3 is a good candidate for being the long-sought tumor suppressor gene located at 19q13 in gliomas and neuroblastomas.
Role of Gastrin Heptadecapeptide in the Acid Secretory Response to Amino Acids in Man
Authors: Mark Feldman, John H. Walsh, Helen C. Wong, Charles T. Richardson
Journal: Journal of Clinical Investigation (1978)

Amino acids and peptides release gastrin and stimulate gastric acid secretion. However, the relation between gastrin release and acid secretory response is unclear. An isotonic mixed amino acid solution (casein hydrolysate) was continuously infused into the stomach of eight healthy human subjects. Acid secretion, measured by in vivo intragastric titration, increased 12.8 meq/h over the response to intragastric infusion of isotonic saline. Plasma gastrin heptadecapeptide (G-17) concentration, measured by specific radioimmunoassay, increased 13 pmol/liter during intragastric amino acid infusion.
Oral Bisphosphonates as Adjuvant Therapy for Operable Breast Cancer
Authors: Trevor Powles, Eugene McCroskey, Alexander Paterson
Journal: Clinical Cancer Research (2006)

Abstract Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures, and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells, which activate osteoclasts to cause bone resorption. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. This vicious circle thereby facilitates the growth of metastases in bone, thus making this a preferential site for relapse. Agents, such as the bisphosphonates, which block osteoclast function, have been shown to reduce the progression of established bone metastases. The oral bisphosphonate clodronate (1,600 mg/d) is effective for treatment of patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for 2 years, clodronate has been reported to significantly reduce the risk of bone metastases during the 2-year study period [19 clodronate patients versus 35 placebo patients; hazard ratio (HR), 0.546; P = 0.03] and 5-year study period (51 clodronate patients versus 73 placebo patients; HR, 0.692; P = 0.04) with a significant reduction in mortality (HR, 0.768; P = 0.048). This benefit, together with the low toxicity and safety of clodronate, supports its use as additional adjuvant therapy for patients with primary breast cancer. Further, similarly designed trials are under way to establish the optimal duration of therapy, the efficacy in stage I disease, and the relative potential of other bisphosphonates, particularly the more powerful aminobisphosphonates, such as ibandronate and zoledronate.
THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS
Authors: Robert L. Hirsch, Aaron Kellner
Journal: The Journal of Experimental Medicine (1956)

Mice rendered hyperlipemic by means of intravenous or subcutaneous injections of triton WR 1339 were found to have an increase in the total amount of cholesterol in their bodies. This observation indicates that the injected surface-active agent affects the metabolism of cholesterol and brings about hyperlipemia by augmenting the synthesis of lipides, or by interfering with their degradation or excretion, or by some combination of these factors. The implications of the findings for the pathogenesis of the hyperlipemia induced by triton are discussed further in the accompanying paper (16).
CD4+CD3− Accessory Cells Costimulate Primed CD4 T Cells through OX40 and CD30 at Sites Where T Cells Collaborate with B Cells
Authors: Mi-Yeon Kim, Fabrina M.C Gaspal, Helen E Wiggett, Fiona M McConnell, Adam Gulbranson-Judge, Chandra Raykundalia, Lucy S.K Walker, Margaret D Goodall, Peter J.L Lane
Journal: Immunity (2003)
Overexpression of Osteopontin Is Associated with More Aggressive Phenotypes in Human Non–Small Cell Lung Cancer
Authors: Zhi Hu, Dongmei Lin, Jingsong Yuan, Ting Xiao, Husheng Zhang, Wenyue Sun, Naijun Han, Ying Ma, Xuebing Di, Meixia Gao, Jinfang Ma, Junhang Zhang, Shujun Cheng, Yanning Gao
Journal: Clinical Cancer Research (2005)

The extracellular matrix (ECM) molecule osteopontin is implicated in many pathologic processes, including inflammation, cell proliferation, ECM invasion, tumor progression, and metastasis. The present study evaluated the clinical and biological importance of osteopontin in human lung cancer.Tissue microarrays derived from non-small cell lung cancer (NSCLC) patients were analyzed immunohistochemically. Osteopontin protein expression was observed in 64.5% (205 of 318) of primary tumors and 75.5% (108 of 143) of lymph node metastases, but in only 27.9% (12 of 43) of normal-appearing bronchial epithelial and pulmonary tissues. Osteopontin expression was associated with tumor growth, tumor staging, and lymph node invasion. In vitro osteopontin enhanced ECM invasion of NSCLC cells, and an osteopontin antibody abolished this effect. We further analyzed osteopontin levels in circulating plasma derived from 158 patients with NSCLC, 54 patients of benign pulmonary disease, and 25 healthy donors, and found that the median osteopontin levels for the three groups were 319.1, 161.6, and 17.9 ng/mL, respectively.Overexpression of osteopontin is common in primary NSCLC and may be important in the development and progression of the cancer. Osteopontin levels in the plasma may serve as a biomarker for diagnosing or monitoring patients with NSCLC.
Clonal selection in xenografted TAM recapitulates the evolutionary process of myeloid leukemia in Down syndrome
Authors: Satoshi Saida, Ken-ichiro Watanabe, Aiko Sato-Otsubo, Kiminori Terui, Kenichi Yoshida, Yusuke Okuno, Tsutomu Toki, RuNan Wang, Yuichi Shiraishi, Satoru Miyano, Itaru Kato, Tatsuya Morishima, Hisanori Fujino, Katsutsugu Umeda, Hidefumi Hiramatsu, Souichi Adachi, Etsuro Ito, Seishi Ogawa, Mamoru Ito, Tatsutoshi Nakahata, Toshio Heike
Journal: Blood (2013)
Single dose tetracycline in cholera.
Authors: M R Islam
Journal: Gut (1987)

A randomised clinical trial was carried out to explore the efficacy of single dose tetracycline therapy in cholera. One hundred and eighteen adult patients were assigned to receive either tetracycline in a single 1 g, or a single 2 g dose, or tetracycline 500 mg every six hours four times, or no antibiotics as controls. The means of total liquid stool volumes after treatment were lower in the single 1 g dose group (168.0 +/- 20.9 ml/kg), in single 2 g dose group (229.5 +/- 45.6 ml/kg), and multiple dose group (214 +/- 28.5 ml/kg), than in the control group (499.1 +/- 56.5 ml/kg) (p less than 0.05). Similarly, the means of durations of diarrhoea and intravenous fluid requirements were significantly lower in the single dose and multiple dose tetracycline groups, than in the controls (p less than 0.05). The mean durations of excretion of Vibrio cholerae were significantly shortened from 3.9 +/- 0.2 days in the control group to 1.9 +/- 0.2 days in single 1 g dose, to 2.2 +/- 0.4 days in single 2 g dose and 1.3 +/- 0.1 days in multiple dose groups, respectively (p less than 0.05). Three patients in the single 1 g dose group and two patients in single 2 g dose group had clinical relapses with excretion of V cholerae during the relapses, but this was not significantly more frequent than that in the multiple dose group (p greater than 0.05). These findings suggest that although multiple dose tetracycline therapy remains the best choice, a single dose of either 1 g or 2 g tetracycline appears to be a reasonable alternative for the treatment of cholera as an adjunct to rehydration therapy.
Resurrection of vitamin D deficiency and rickets
Authors: M. F. Holick
Journal: Journal of Clinical Investigation (2006)

The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children.
Tumor-Associated Macrophages Press the Angiogenic Switch in Breast Cancer
Authors: Elaine Y. Lin, Jeffrey W. Pollard
Journal: Cancer Research (2007)

Abstract The development of a supportive vasculature is essential for tumor progression. In a mouse model of breast cancer, we found that tumor-associated macrophages that are recruited to the tumor just before malignant conversion are essential for the angiogenic switch. These findings establish a causal linkage to explain well-documented clinical correlations between macrophages, microvessel density, and poor prognosis in breast tumors. [Cancer Res 2007;67(11):5064–3]
Targeted next-generation sequencing expands the spectrum of mitochondrial disorders
Authors: Si Hahn
Journal: Genome Medicine (2012)

Next-generation sequencing has become a powerful tool for testing genetically and clinically heterogeneous conditions such as mitochondrial disorders. A recent study published in Science Translational Medicine underscores the considerable clinical benefits of targeted next-generation sequencing for the diagnosis of mitochondrial disorders. The findings also suggest that the genetic heterogeneity that can result in mitochondrial disease appears much broader than previously thought.
Managing convulsions with fever
Authors: B Thalayasingam
Journal: BMJ (1991)

obese subjects than in controls of normal weight (p<O0-OOl), and there was a correlation between Lp(a) and fibrinogen concentrations (r=0 523), Lp(a) and cholesterol concentrations (r=0 273), and Lp(a) concentration and body mass index (r= 0-210).We conclude that the increased values among obese patients and a significant correlation with other important risk factors for atherosclerosis show that Lp(a) concentration can be considered to be a "trouble marker" of coronary heart disease.
Obsessions and Compulsions in the Community: Prevalence, Interference, Help-Seeking, Developmental Stability, and Co-Occurring Psychiatric Conditions
Authors: Miguel A. Fullana, David Mataix-Cols, Avshalom Caspi, Honalee Harrington, Jessica R. Grisham, Terrie E. Moffitt, Richie Poulton
Journal: American Journal of Psychiatry (2009)

It is unclear how many people in the community have obsessions and compulsions and associated levels of interference. It is also unknown what variables predict help-seeking for these symptoms, whether they are developmentally stable, and whether they increase the risk of mental disorders.The authors analyzed data from the prospective longitudinal Dunedin study of an unselected birth cohort. The presence of obsessions and compulsions and mental disorders was assessed using the Diagnostic Interview Schedule (DIS) at ages 11, 26, and 32. Data on interference and help-seeking were obtained at ages 26 and 32.Obsessions and compulsions were frequent in individuals with mental disorders other than obsessive-compulsive disorder (OCD) and among people without mental disorders. Even in the latter group, these symptoms caused significant interference. The presence of anxiety/depression and of obsessions (particularly aggressive and shameful thoughts), but not compulsions, was associated with help-seeking. Harm/checking was the most prevalent symptom dimension. Symptom dimensions were temporally stable and associated with increased comorbidity. Obsessive-compulsive symptoms at age 11 predicted a high risk of an adult OCD diagnosis as well as elevated adult symptom dimensions.Obsessions and compulsions are common in the adult population, have their roots in childhood, and are associated with interference, risk for disorders, and help-seeking. Subclinical obsessions and compulsions should be taken into account in research, intervention, and DSM-V.
A Molecular Diagnostic Test for Distinguishing Lung Adenocarcinoma from Malignant Mesothelioma Using Cells Collected from Pleural Effusions
Authors: Andrew J. Holloway, Dileepa S. Diyagama, Ken Opeskin, Jenette Creaney, Bruce W.S. Robinson, Richard A. Lake, David D.L. Bowtell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Patients with malignant mesothelioma or adenocarcinoma of the lung often present with respiratory complications associated with a malignant pleural effusion. Distinguishing between these malignancies is frequently problematic, as many of the clinical, cytologic, and histologic features of the diseases overlap. Following cytologic analysis of pleural effusions, subsequent confirmatory tissue biopsies involve increased patient morbidity and expense. We have therefore designed a gene expression–based test to classify the primary tumor causing a malignant pleural effusion, using cells collected from the effusion itself. Experimental Design: We have used microarray data for 190 lung adenocarcinomas and 33 malignant mesotheliomas to identify genes differentially expressed between the two diseases. Genes expressed in normal mesothelial cells were removed, allowing the development of a PCR-based test to measure the expression of genes that discriminate between mesothelioma and lung adenocarcinoma from cytology specimens. Results: Applying an real-time PCR–based assay involving 17 genes to 13 independent samples from biopsy-proven malignant mesothelioma and lung adenocarcinomas resulted in the correct identification of all samples. Conclusions: We have developed a test that is able to distinguish between lung adenocarcinoma and mesothelioma in cells collected from pleural effusions.
Does delayed gastric emptying really cause symptoms in functional dyspepsia? We still doubt it! * Author's reply
Authors: N J Talley, G R Locke, J Tack, M Camilleri
Journal: Gut (2006)

We enjoyed reading the provocative commentary by Camilleri ( Gut 2006; 55 :909–10) on our large study of patients with functional dyspepsia ( Gut 2006; 55 :933–9). We completely agree that delayed gastric emptying is a marker of disturbed pathophysiology in functional dyspepsia; indeed, we first reported this observation in 1989.1 However, we remain unconvinced, based on the available data, that this abnormality alone is linked to upper gastrointestinal symptoms.1–3 Factor analysis studies from the general population, in the absence of objective testing, do not provide insights into this issue,4,5 although we have shown that non-consulters with dysmotility-like dyspepsia are more likely to have gastric emptying delay.6 Studies from selected tertiary care patients are of interest, but Camilleri has previously reported negative results.3 Importantly, in a previous study of 551 patients with functional dyspepsia and 247 patients with type I diabetes and postprandial dyspepsia, gastric emptying, as measured by C13 octanoic acid breath testing, was …
African Tick-Bite Fever after a Game-Hunting Expedition
Authors: Benjamin R Bohaty, Adelaide A Hebert
Journal: New England Journal of Medicine (2015)

A 15-year-old girl was admitted to the hospital with a persistent fever, headache, and myalgia. A solitary, painful, black, crusted ulcer with a peripheral erythematous halo was noted in the left popliteal fossa; the ulcer had begun as an asymptomatic erythematous papule 1 week previously.
The Relationship between Pulmonary Artery Wedge Pressure and Left Atrial Pressure in Man
Authors: D. C. CONNOLLY, J. W. KIRKLIN, E. H. WOOD
Journal: Circulation Research (1954)

In 17 patients with atrial septal defect, in 12 patients with mitral stenosis and in four patients with unilateral lung tumor but without evidence of mitral valve disease, a similarity in pressure pulse contours in the left atrium and pulmonary artery wedge position was obtained at cardiac catheterization.It is concluded that the pulmonary artery wedge pressure pulse is a reasonably accurate reflection both in magnitude and in contour of the left atrial pressure pulse in man during normal respiration and also during assisted respiration at operation.N UMEROUS reports have been published concerning the relationship between the pulmonary artery wedge pressure and the left atrial pressure.Good correlation and considerable variation in the correlation have been variously reported between these pressures, measured consecutively in patients with atrial septal defect or simultaneously in experimental animals, so that considerable uncertainty still exists 1 ' 2 concerning the significance of pulmonary artery wedge pressures.Simultaneous recordings of pulmonary artery wedge and left atrial pressures in humans have been reported in previous communications from this laboratory. 3* 5It is the purpose of this paper to present our experience with the comparison of pulmonary artery wedge pressure and left atrial pressure measurements in 33 patients.In 17 cases these pressures were measured consecutively during routine cardiac catheterization of patients with atrial septal defect, and in 1(5 cases the pressures were measured simultaneously during operation on patients with mitral stenosis or lung tumor.
Microalbuminuria and Cardiovascular Autonomic Dysfunction Are Independently Associated With Cardiovascular Mortality: Evidence for Distinct Pathways
Authors: Hanneke J.B.H. Beijers, Isabel Ferreira, Bert Bravenboer, Jacqueline M. Dekker, Giel Nijpels, Robert J. Heine, Coen D.A. Stehouwer
Journal: Diabetes Care (2009)

OBJECTIVE Microalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality. RESEARCH DESIGN AND METHODS We studied 490 individuals from a population-based cohort of individuals aged 50–75 years who were followed for a median period of 13.6 years. Microalbuminuria was defined as an albumin-to-creatinine ratio ≥2.0 mg/mmol in an early-morning spot-urine sample. Ten parameters reflecting different aspects of cardiovascular autonomic function were measured and compiled into a total score of C-AD (mean of separate z scores). The association between C-AD and microalbuminuria was estimated by multiple linear regression, and relative risks (RRs) for cardiovascular mortality were estimated by Cox proportional hazards analyses. RESULTS After adjustments for age, sex, glucose tolerance status, and other risk factors, C-AD was associated with microalbuminuria (β = 0.16 [95% CI 0.01–0.33]), and both microalbuminuria (RR 2.09 [1.07–4.08]) and C-AD (1.74 [1.04–2.89]) were associated with cardiovascular mortality. These associations did not change after further mutual adjustment for C-AD (2.13 [1.09–4.17]) or microalbuminuria (1.76 [1.05–2.94]), respectively. CONCLUSIONS Both microalbuminuria and C-AD are independently associated with cardiovascular mortality, and the excess mortality attributable to microalbuminuria cannot be explained by C-AD.
Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells.
Authors: M C Seguin, F W Klotz, I Schneider, J P Weir, M Goodbary, M Slayter, J J Raney, J U Aniagolu, S J Green
Journal: The Journal of Experimental Medicine (1994)

Exposure of BALB/c mice to mosquitoes infected with irradiated Plasmodium berghei confers protective immunity against subsequent sporozoite challenge. Immunized mice challenged with viable sporozoites develop parasitemia when treated orally with substrate inhibitors of nitric oxide synthase (NOS). This suggests that the production of nitric oxide (NO) prevents the development of exoerythrocytic stages of malaria in liver. Liver tissue from immunized mice expressed maximal levels of mRNA for inducible NOS (iNOS) between 12 and 24 h after challenge with sporozoites. Intraperitoneal injection of neutralizing monoclonal antibody against interferon gamma (IFN-gamma) or in vivo depletion of CD8+ T cells, but not CD4+ T cells, at the time of challenge blocked expression of iNOS mRNA and ablated protection in immunized mice. These results show that both CD8+ T cells and IFN-gamma are important components in the regulation of iNOS in liver which contributes to the protective response of mice immunized with irradiated malaria sporozoites. IFN-gamma, likely provided by malaria-specific CD8+ T cells, induces liver cells, hepatocytes and/or Kupffer cells, to produce NO for the destruction of infected hepatocytes or the parasite within these cells.