tbuckley/cabot-search huggingface dataset:
Low serum testosterone as an indicator of metastatic bronchial carcinoma.
Authors: D P Taggart, C Gray, K G Davidson, A Faichney
Journal: Thorax (1987)

Serum testosterone concentrations were measured preoperatively in 39 men undergoing thoracotomy for histologically proved bronchial carcinoma, in 10 patients with pulmonary opacities that transpired to be non-malignant (benign group) and in 23 men were undergoing minor elective surgical procedures (control group). Thirteen of the 39 patients with known bronchial carcinoma were considered to have had curative surgery and 26 a palliative procedure when operative and pathological findings were taken into consideration. Low serum testosterone concentrations (less than 12 nmol/l) were detected in four patients in the curative group, in 22 in the palliative group (chi 2 test: p less than 0.001), three in the benign group, and in two patients in the control group. A low serum testosterone concentration in patients with bronchial carcinoma may be an indicator of metastatic disease and sequential serum testosterone estimations may prove useful in the follow up of patients thought to have undergone curative surgery.
The Prevalence and Pattern of Complementary and Alternative Medicine Use in Individuals With Diabetes
Authors: Leonard E. Egede, Xiaobou Ye, Deyi Zheng, Marc D. Silverstein
Journal: Diabetes Care (2002)

OBJECTIVE—This study compared the prevalence and pattern of use of complementary and alternative medicine (CAM) in individuals with and without diabetes and identified factors associated with CAM use. RESEARCH DESIGN AND METHODS—The 1996 Medical Expenditure Panel Survey, a nationally representative sample of the U.S. noninstitutionalized civilian population, was analyzed. Estimates of CAM use in individuals with common chronic conditions were determined, and estimates of CAM use in patients with diabetes were compared with that in individuals with chronic medical conditions. Patterns of use and costs of CAM use in patients with diabetes were compared with those in nondiabetic individuals. Multiple logistic regression was used to determine independent predictors of CAM use in individuals with diabetes, controlling for age, sex, race/ethnicity, household income, educational level, and comorbidity. RESULTS—Individuals with diabetes were 1.6 times more likely to use CAM than individuals without diabetes (8 vs. 5%, P &amp;lt; 0.0001). In the general population, estimates of CAM use were not significantly different across selected chronic medical conditions, but diabetes was an independent predictor of CAM use. Among individuals with diabetes, older age (≥65 years) and higher educational attainment (high school education or higher) were independently associated with CAM use. CONCLUSIONS—Diabetes is an independent predictor of CAM use in the general population and in individuals with diabetes. CAM use is more common in individuals aged ≥65 years and those with more than high school education.
C-Myc and its target FoxM1 are critical downstream effectors of constitutive androstane receptor (CAR) mediated direct liver hyperplasia
Authors: William E. Blanco‐Bose, Mark J. Murphy, Armin Ehninger, Sandra Offner, Christelle Dubey, Wendong Huang, David D. Moore, Andreas Trumpp
Journal: Hepatology (2008)

In the adult liver, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), an agonist of the constitutive androstane receptor (CAR, NR1I3), produces rapid hepatomegaly in the absence of injury. In this study, we identify c-Myc as a gene induced by CAR and demonstrate that TCPOBOP-induced proliferation of hepatocytes depends on c-Myc function. Moreover, the TCPOBOP-induced cell cycle program (Cdc2, cyclins, MCM proteins, Cdc20, and genes implicated in the spindle assembly checkpoint) is severely impaired in c-Myc mutant livers. Strikingly, many of these genes overlap with a program controlled by the forkhead transcription factor FoxM1, known to control progression through S-phase and mitosis. Indeed, FoxM1 is also induced by TCPOBOP. Moreover, we show that c-Myc binds to the FoxM1 promoter in a TCPOBOP-dependent manner, suggesting a CAR → c-Myc → FoxM1 pathway downstream of TCPOBOP. Conclusion: Collectively, this study identifies c-Myc and FoxM1 mediated proliferative programs as key mediators of TCPOBOP-CAR induced direct liver hyperplasia. (HEPATOLOGY 2008.)
Activated Checkpoint Kinase 2 Provides a Survival Signal for Tumor Cells
Authors: Jagadish C. Ghosh, Takehiko Dohi, Christopher M. Raskett, Timothy F. Kowalik, Dario C. Altieri
Journal: Cancer Research (2006)

Abstract Tumor cells often become resistant to DNA damage–based therapy; however, the underlying mechanisms are not yet understood. Here, we show that tumor cells exposed to DNA damage counteract cell death by releasing the antiapoptotic protein, survivin, from mitochondria. This is independent of p53, and requires activated checkpoint kinase 2 (Chk2), a putative tumor suppressor. Molecular or genetic targeting of Chk2 prevents the release of survivin from mitochondria, enhances DNA damage–induced tumor cell apoptosis, and inhibits the growth of resistant in vivo tumors. Therefore, activated Chk2 circumvents its own tumor-suppressive functions by promoting tumor cell survival. Inhibiting Chk2 in combination with DNA-damaging agents may provide a rational approach for treating resistant tumors. (Cancer Res 2006; 66(24): 11576-9)
Importance of minor histocompatibility antigen expression by nonhematopoietic tissues in a CD4+ T cell–mediated graft-versus-host disease model
Authors: Stephen C. Jones, George F. Murphy, Thea M. Friedman, Robert Korngold
Journal: Journal of Clinical Investigation (2003)

Minor histocompatibility antigens with expression restricted to the recipient hematopoietic compartment represent prospective immunological targets for graft-versus-leukemia therapy. It remains unclear, however, whether donor T cell recognition of these hematopoietically derived minor histocompatibility antigens will induce significant graft-versus-host disease (GVHD). Using established bone marrow irradiation chimeras across the multiple minor histocompatibility antigen-disparate, C57BL/6-->BALB.B combination, we studied the occurrence of lethal GVHD mediated by CD4+ T cells in recipient mice expressing only hematopoietically derived alloantigens. Even substantial dosages of donor C57BL/6 CD4+ T cells were unable to elicit lethal GVHD when transplanted into [BALB.B-->C57BL/6] chimeras. Instead, chimeric mice displayed transient cachexia with reduced target-tissue injury over time, reflecting an early, limited, graft-versus-host response. On the other hand, the importance of minor histocompatibility antigens derived from nonhematopoietic tissues was demonstrated by the finding that [C57BL/6-->BALB.B] chimeric mice succumbed to C57BL/6 CD4+ T cell-mediated GVHD. These data suggest that severe acute CD4+ T cell-mediated GVHD across this minor histocompatibility antigen barrier depends on the expression of nonhematopoietically rather than hematopoietically derived alloantigens for maximal target-tissue infiltration and injury.
Maleic acid and succinic acid in fermented alcoholic beverages are the stimulants of gastric acid secretion
Authors: Stephan Teyssen, Gloria González-Calero, Michael Schimiczek, Manfred V. Singer
Journal: Journal of Clinical Investigation (1999)

Alcoholic beverages produced by fermentation (e.g., beer and wine) are powerful stimulants of gastric acid output and gastrin release in humans. The aim of this study was to separate and specify the gastric acid stimulatory ingredients in alcoholic beverages produced by fermentation. Yeast-fermented glucose was used as a simple model of fermented alcoholic beverages; it was stepwise separated by different methods of liquid chromatography, and each separated solution was tested in human volunteers for its stimulatory action on gastric acid output and gastrin release. Five substances were detected by high-performance liquid chromatography and were analyzed by mass spectrometry and 1H-13C nuclear magnetic resonance spectroscopy. At the end of the separation process of the five identified substances, only the two dicarboxylic acids, maleic acid and succinic acid, had a significant (P < 0.05) stimulatory action on gastric acid output (76% and 70% of fermented glucose, respectively), but not on gastrin release. When given together, they increased gastric acid output by 100% of fermented glucose and by 95% of maximal acid output. We therefore conclude that maleic acid and succinic acid are the powerful stimulants of gastric acid output in fermented glucose and alcoholic beverages produced by fermentation, and that gastrin is not their mediator of action.
Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene and Arterial Oxygen Saturation at High Altitude
Authors: David R. Woods, Andrew J. Pollard, David J. Collier, Yalda Jamshidi, Vassilis Vassiliou, Emma Hawe, Steve E. Humphries, Hugh E. Montgomery
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

There is a significant genetic influence on arterial oxygen saturation (SaO2) in high-altitude (HA) residents. It is not known whether this is true of lowlanders ascending to HA. The I allele of the angiotensin-converting enzyme (ACE) gene is associated with low ACE activity and elite endurance performance. An excess of the I allele has also been reported in South American natives living over 3,000 m and among elite HA mountaineers who demonstrate extreme endurance in a hypoxic environment, where maintenance of SaO2 is crucial to performance. We postulated that the I allele may confer an advantage at HA through genotype-dependent alterations in SaO2. Rapid ascent (n = 32) and slow ascent groups (n = 40), ascending to approximately 5,000 m over 12.0 and 18.5 days, respectively, had their SaO2 assessed throughout and compared with their ACE genotype. Resting SaO2 was independent of the ACE genotype and remained so for the slow ascent group, in whom the fall in SaO2 with ascent was genotype independent. However, SaO2 with ascent was significantly associated with the ACE genotype in the rapid ascent group (p = 0.01) with a relatively sustained SaO2 in the II subjects. These data are the first to report an association of the I allele with the maintenance of SaO2 at HA.
Assessment of core stability in Indian women wrestling team and its relationship to low back pain
Authors: Jahnavi Dande, Sandipan Das Sharma, Manabendra Bhattacharyya
Journal: British Journal of Sports Medicine (2010)

Wrestling is a dynamic and highly demanding sport. Core stability is predominantly maintained by dynamic function of muscular elements, which act as a bridge between upper limbs and lower limbs to transfer force and maintaining lumbo pelvic stability. Decreased core stability was reported to be associated with higher risk of low back injuries. This study aims to validate a static and dynamic core stability value of Indian woman wrestlers and to establish a correlation between stability score and low back pain. Twenty-eight Indian women national camper wrestlers participated in the study. They were subjected to tests of core stability, which included static core stability tests (Bliss test protocol) and dynamic core stability tests (isoinertial tests). Mean values are established and compared with international standardised values and endurance ratios. Low back pain was evaluated by Oswestry low back pain disability questionnaire and severity graded by Japanese Orthopedics Association back pain evaluation questionnaire. The results are correlated to identify the relationship with low back pain. This pilot comparative study shows significant disparity between flexor and extensor score in comparison with international standards. The p value is &lt;0.05 and predict a direct correlation to biomechanical error of lumbo-pelvic segment.
Epigenetic-Genetic Interactions in the<i>APC/WNT, RAS/RAF</i>, and<i>P53</i>Pathways in Colorectal Carcinoma
Authors: Yutaka Suehiro, Chi Wai Wong, Lucian R. Chirieac, Yutaka Kondo, Lanlan Shen, C. Renee Webb, Yee Wai Chan, Annie S.Y. Chan, Tsun Leung Chan, Tsung-Teh Wu, Asif Rashid, Yuichiro Hamanaka, Yuji Hinoda, Rhonda L. Shannon, Xuemei Wang, Jeffrey Morris, Jean-Pierre J. Issa, Siu Tsan Yuen, Suet Yi Leung, Stanley R. Hamilton
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Early events in colorectal tumorigenesis include mutation of the adenomatous polyposis coli (APC) gene and epigenetic hypermethylation with transcriptional silencing of the O6-methylguanine DNA methyltransferase (MGMT), human mut L homologue 1 (hMLH1), and P16/CDKN2A genes. Epigenetic alterations affect genetic events: Loss of MGMT via hypermethylation reportedly predisposes to guanine-to-adenine or cytosine-to-thymine (G:C→A:T) transition mutations in KRAS and P53, and silencing of hMLH1 leads to high levels of microsatellite instability (MSI-H)/mutator phenotype, suggesting that epigenetic-genetic subtypes exist. Experimental Design: We evaluated the relationships of aberrant methylation of APC, MGMT, hMLH1, P16, N33, and five MINTs to mutations in APC, KRAS, BRAF, and P53 in 208 colorectal carcinomas. Results: We found that APC hypermethylation was age related (P = 0.04), in contrast to the other genes, and did not cluster with CpG island methylator phenotype (CIMP) markers. Hypermethylation of APC concurrently with either MGMT or hMLH1 was strongly associated with occurrence of G-to-A transitions in APC [odds ratio (OR), 26.8; P &amp;lt; 0.0002 from multivariable logic regression model], but C-to-T transitions had no associations. There was no relationship of hypermethylation of any gene, including MGMT, with G-to-A or C-to-T transitions in KRAS or P53, although APC hypermethylation was associated with P53 mutation (P &amp;lt; 0.0002). CIMP with MSI-H due to hMLH1 hypermethylation, or CIMP with loss of MGMT expression in non–MSI-H tumors, was associated with BRAF mutation (OR, 4.5; P &amp;lt; 0.0002). CIMP was also associated with BRAF V600E T-to-A transversion (OR, 48.5; P &amp;lt; 0.0002). Conclusions: Our findings suggest that the heterogeneous epigenetic dysregulation of promoter methylation in various genes is interrelated with the occurrence of mutations, as manifested in epigenetic-genetic subgroups of tumors.
Re: CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women With Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial and Re: CYP2D6 and UGT2B7 Genotype and Risk of Recurrence in Tamoxifen-Treated Breast Cancer Patients
Authors: P. D. P. Pharoah, J. Abraham, C. Caldas
Journal: JNCI Journal of the National Cancer Institute (2012)
The Human Gene Mutation Database: 2008 update
Authors: Peter D Stenson, Matthew Mort, Edward V Ball, Katy Howells, Andrew D Phillips, Nick ST Thomas, David N Cooper
Journal: Genome Medicine (2009)

Abstract The Human Gene Mutation Database (HGMD ® ) is a comprehensive core collection of germline mutations in nuclear genes that underlie or are associated with human inherited disease. Here, we summarize the history of the database and its current resources. By December 2008, the database contained over 85,000 different lesions detected in 3,253 different genes, with new entries currently accumulating at a rate exceeding 9,000 per annum. Although originally established for the scientific study of mutational mechanisms in human genes, HGMD has since acquired a much broader utility for researchers, physicians, clinicians and genetic counselors as well as for companies specializing in biopharmaceuticals, bioinformatics and personalized genomics. HGMD was first made publicly available in April 1996, and a collaboration was initiated in 2006 between HGMD and BIOBASE GmbH. This cooperative agreement covers the exclusive worldwide marketing of the most up-to-date (subscription) version of HGMD, HGMD Professional, to academic, clinical and commercial users.
Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis.
Authors: M Cabrera, M A Shaw, C Sharples, H Williams, M Castes, J Convit, J M Blackwell
Journal: The Journal of Experimental Medicine (1995)

Recent studies have shown that mucocutaneous leishmaniasis (MCL), a severe and debilitating form of American cutaneous leishmaniasis (ACL) caused by Leishmania braziliensis infection, is accompanied by high circulating levels of tumor necrosis factor (TNF)-alpha. Analysis of TNF polymorphisms in Venezuelan ACL patients and endemic unaffected controls demonstrates a high relative risk (RR) of 7.5 (P &amp;lt; 0.001) of MCL disease in homozygotes for allele 2 of a polymorphism in intron 2 of the TNF-beta gene, especially in females (RR = 9.5; P &amp;lt; 0.001) compared with males (RR = 4; P &amp;lt; 0.05). A significantly higher frequency (P &amp;lt; 0.05) of allele 2 at the -308-basepair TNF-alpha gene polymorphism was also observed in MCL patients (0.18) compared with endemic control subjects (0.069), again associated with a high relative risk of disease (RR = 3.5; P &amp;lt; 0.05) even in the heterozygous condition. Because both the TNF-alpha and TNF-beta polymorphisms have previously been linked with functional differences in TNF-alpha levels, these data suggest that susceptibility to the mucocutaneous form of disease may be directly associated with regulatory polymorphisms affecting TNF-alpha production.
Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma
Authors: Luxia Tu, Zhen Liu, Xiufang He, Ying He, Huiling Yang, Qingping Jiang, Siming Xie, Guanghui Xiao, Xin Li, Kaitai Yao, Weiyi Fang
Journal: Molecular Cancer (2010)

Abstract Background The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 ( EIF4G1 ) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including patients' survival time. Methods Using real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated. Results The expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells ( P &lt; 0.001). Immunohistochemical analysis revealed that the expression of EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues ( P &lt; 0.001). In addition, the levels of EIF4G1 protein in tumors were positively correlated with tumor T classification ( P = 0.039), lymph node involvement (N classification, P = 0.008), and the clinical stages ( P = 0.003) of NPC patients. Patients with higher EIF4G 1 expression had shorter overall survival time ( P = 0.019). Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth. Conclusion Our data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.
CD1d-restricted Recognition of Synthetic Glycolipid Antigens by Human Natural Killer T Cells
Authors: Franca M. Spada, Yasuhiko Koezuka, Steven A. Porcelli
Journal: The Journal of Experimental Medicine (1998)

A conserved subset of mature circulating T cells in humans expresses an invariant Vα24-JαQ T cell receptor (TCR)-α chain rearrangement and several natural killer (NK) locus–encoded C-type lectins. These human T cells appear to be precise homologues of the subset of NK1.1+ TCR-α/β+ T cells, often referred to as NK T cells, which was initially identified in mice. Here we show that human NK T cell clones are strongly and specifically activated by the same synthetic glycolipid antigens as have been shown recently to stimulate murine NK T cells. Responses of human NK T cells to these synthetic glycolipids, consisting of certain α-anomeric sugars conjugated to an acylated phytosphingosine base, required presentation by antigen-presenting cells expressing the major histocompatibility complex class I–like CD1d protein. Presentation of synthetic glycolipid antigens to human NK T cells required internalization of the glycolipids by the antigen-presenting cell and normal endosomal targeting of CD1d. Recognition of these compounds by human NK T cells triggered proliferation, cytokine release, and cytotoxic activity. These results demonstrate a striking parallel in the specificity of NK T cells in humans and mice, thus providing further insight into the potential mechanisms of immune recognition by NK T cells and the immunological function of this unique T cell subset.
Latent TGF-β1 Protects Against Crescentic Glomerulonephritis
Authors: Xiao R. Huang, Arthur C.K. Chung, Li Zhou, Xiao J. Wang, Hui Y. Lan
Journal: Journal of the American Society of Nephrology (2008)

Despite the critical role that TGF-beta plays in renal fibrosis, transgenic mice that overexpress human latent TGF-beta1 in the skin exhibit normal renal histology and function even though circulating levels of latent TGF-beta1 are an order of magnitude higher than wild-type animals. In fact, latent TGF-beta1 seems to protect against renal inflammation in a model of ureteral obstruction. It is unknown, however, whether latent TGF-beta1 also has this effect in immunologically mediated forms of renal disease such as anti-GBM crescentic glomerulonephritis. We induced anti-GBM disease in wild-type and transgenic mice overexpressing latent TGF-beta1 in keratinocytes. After 14 days, wild-type mice developed progressive crescentic glomerulonephritis with severe renal inflammation and fibrosis. In transgenic mice, proteinuria was reduced by 50%, renal function was preserved, and the formation of glomerular crescents was suppressed by 70%. In addition, transgenic animals had reduced renal inflammation, evidenced by a 70% decrease in the accumulation of T cells and macrophages, and reduced expression of renal IL-1beta, TNFalpha, and MCP-1 by 70 to 80%. Progressive renal fibrosis was also prevented in the transgenic mice, and these protective effects were associated with elevated levels of latent, but not active, TGF-beta1 in plasma and renal tissue. Renal Smad7 was up-regulated and both NF-kappaB and TGF-beta/Smad2/3 activation were suppressed. In conclusion, mice overexpressing latent TGF-beta1 in the skin were protected against anti-GBM crescentic glomerulonephritis, possibly via Smad 7-mediated inhibition of NF-kappaB-dependent renal inflammation and TGF-beta/Smad2/3-dependent fibrosis.
Surgical treatment of GIST – An institutional experience of a high-volume center
Authors: Katrin Schwameis, Alexandra Fochtmann, Michael Schwameis, Reza Asari, Sophie Schur, Wolfgang Köstler, Peter Birner, Ahmed Ba-Ssalamah, Johannes Zacherl, Fritz Wrba, Thomas Brodowicz, Sebastian Friedrich Schoppmann
Journal: International Journal of Surgery (2013)