tbuckley/cabot-search huggingface dataset:
Four new novel mutations in SRY (sex determining region) and WT1 (Wilms tumor 1) genes in two sisters with sex reversal and gonadal tumor formation with 46,XY chromosomal constitution.
Authors: Mohammad Shahid, Mohd. Aslam, V. S. Dhillion, Mohd. Raish, Nida J. Khan, Rahimunnisa Praveen, Arif Ahmad, Syed Akhtar Husain
Journal: Clinical Cancer Research (2006)

A23   In mammals, a master gene located on the Y-chromosome, the testis-determining gene SRY, controls sex determination. Mutation in testis-determining gene (SRY) result in XY sex reversal with pure gonadal dysgenesis. XY gonadal dysgenesis can be classified as either complete or incomplete according to gonadal morphology. The disease is a sex reversal disorder resulting from embryonic testicular regression sequences and is induced by mutations in the sex determining region (SRY) gene. Mutation in SRY gene has been considered to account for only 10-15% of 46,XY gonadal dysgenesis cases whereas the remaining majority may have mutation (s) in the SRY regulatory elements or other genes involved in sex differentiation pathways. Using polymerase chain reaction (PCR), single strand conformational polymorphism (SSCP) and automated DNA sequencing, we searched the mutations in SRY and WT1 genes from two sisters with complete form of XY gonadal dysgenesis and detected four novel mutations in SRY and WT1 genes. Patient no. 1 demonstrated two mutations (Nucleotide G_>C substitution and T deletion at codon no 118 and 127, replacing Alanine (A)at codon 118 with proline (P) and Tyrosin (T) at codon 127 with Ileucin (I) respectively) with in HMG-box of SRY with WT1 genes. On the other hand patient no. 2 also showed one mutation (Nucleotide A ⋄ T substitution at codon no. 92 replacing lysine (K) with methione (M) within HMG box of SRY gene without any mutation in WT1 gene. Altered SSCP pattern were also observed in these patients. Histological examination of gonads in patient revealed the formation of gonadoblastoma. In present study we observed malignant dysgenesis germinoma lesion was observed in patient no 1 (28 yrs) with aberrant SRY and WT1 genes but no tumor formation was observed in another younger patient (22 yrs) with aberrant SRY and normal WT1 genes. Therefore the incidence of gonadoblastoma formation increases with age in XY sex reversal patients. On the basis of these results it is recommend that XY female should be identified prepubertally because delay diagnosis may bring about the development of gonadal tumor and clinician carefully examine and observe the gonads of patients with aberrant SRY and WT1 genes.
Clinical Nutrition: Enteral and Tube Feeding
Authors: John L. Rombeau, Rolando H Rolandelli
Journal: Annals of Internal Medicine (1991)

History of EN. Physiology of the GI Tract. Protein Metabolism. Lipid Metabolism. Carbohydrate Metabolism. Dietary Fiber. Micronutrients. Therapeutic Effects of Nutrient. The Molecular Basis of EN and the Gut. Assessment of the Nutritional Status. Endoscopic and Laparoscopic Access to the GI Tract. Radiologic Techniques for Access to the GI Tract. Defined Formula Diets. Delivering Systems and Administration of Tube Feedings. EN of the Surgical Patient. EN and the Neurological Diseases. EN and Cancer. EN in Trauma and Critical Illness. EN in Burns. EN in Pediatrics. EN in AIDS. EN in the Elderly. EN in Gastrointestinal Disease. EN in Liver Disease. EN and Pancreatic Disease. EN in Renal Disease. EN in Diabetes. EN and Respiratory Diseases. EN and Transplantation. Home EN in the Adult. Home EN in Pediatrics. Nutrient-Drug Interaction. Diarrhea and Enteral Nutrition. Monitoring the Patient Receiving EN. Short Bowel. Ethics and the Therminally Ill. Enteral Nutrition and Managed Care.
Abstract 10693: Identification of Lunasin as the Active Component in Soy Protein Responsible for Reducing LDL Cholesterol and Risk of Cardiovascular Disease
Authors: Alfredo F Galvez
Journal: Circulation (2012)

Soy protein has an approved FDA health claim for reducing LDL cholesterol and CVD risk but the active component and mechanism of action are unknown. We tested the hypothesis that the lunasin peptid...
Abstract 12790: Impaired Extracellular Matrix Turnover is Ameliorated by Exercise Training in Short-Term Experimental Diabetic Cardiomyopathy
Authors: Flávio S Silva, Diego N Araújo, Raul H Bortolin, João Paulo M Silva, Adriana A Rezende, Bento A Abreu, Fernando A Dias
Journal: Circulation (2014)

The importance of exercise training (ExT) in treatment of diabetic cardiomyopathy has been reported in recent studies; however, only limited data can be found regarding the effects of exercise training on early stages of left ventricle (LV) remodeling in diabetes mellitus (DM). We hypothesized that ExT could attenuate the early LV remodeling induced by experimental DM. Male Wistar rats were divided in 4 groups: sedentary control (SC, n=9), trained control (TC, n=13), sedentary diabetic (SD, n=20) and trained diabetic (TD, n=17). Diabetes was induced by streptozotocin (45 mg/kg, i.v.). Training program was initiated at the onset of DM and consisted of 4 weeks running on a treadmill (13 m/min, 60 min/day, 5 days/week). Deaths were registered during the 4-week period. At the end of the experiments, hearts were collected (n=8-10/group) for histological analysis of LV morphology (hematoxylin-eosin staining) and collagen content (picrosirius red staining). Also, fresh LV fragments were isolated for gene expression analysis of the following interstitial proteins: collagens types I and III, metalloproteinases (MMPs) 2 and 9, and transforming growth factor (TGF)-1. We verified high mortality in SD animals (60% vs. 0% in SC, p 0.05 vs. SC). SD group also showed an increase in both cross-sectional area (mean±SEM) of myocytes (SD: 227.65 ± 3.10um 2  and SC: 213.06 ± 2.69um 2 , p 2 , p 0.05). Analysis of gene expression revealed downregulation of collagen I (2.9-fold) and III (6.7-fold), as well as lower expression of MMP-2 (2.3-fold) in SD (p 0.05). MMP-2 (2.8-fold) and TGF-1 (4.5-fold) were upregulated only in TC group (p
Drug-Drug Interactions in Patients Co-infected With HCV and HIV
Authors: Yuichi Nozaki, Mikio Yanase, Naohiko Masaki
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy
Authors: DE Reece, MJ Barnett, JD Shepherd, DE Hogge, RJ Klasa, SH Nantel, HJ Sutherland, HG Klingemann, RN Fairey, NJ Voss
Journal: Blood (1995)
624. Effect of an Oncolytic HSV Mutant Expressing ICP34.5 under Control of a Nestin Promoter for Brain Tumor Therapy
Authors: Hirokazu Kambara, Hideyuki Okano, E. Antonio Chiocca, Yoshinaga Saeki
Journal: Molecular Therapy (2004)

HSV mutants (e.g. G207 and MGH1), possessing deletions in both copies of the ICP34.5 gene and an insertional mutation in the ICP6 gene (ribonucleotide reductase), have proven safe through a number of animal experiments and clinical trials. Although these double mutants clearly demonstrate oncolytic effects as well as anti-tumor immunization, their oncolytic effects are markedly reduced. ICP34.5-null viruses fail to grow in a variety of cultured cells due to their inability to prevent RNA-dependent protein kinase (PKR)-mediated inhibition of protein synthesis. In HSV-infected cells, viral double-stranded RNA will activate PKR by autophosphorylation, and activated PKR phosphorylates eIF-2a, which inhibits initiation of protein translation within the cells and in turn inhibits viral replication. The ICP34.5 dephosphorylates eIF-2a, thus allowing continued protein synthesis and viral replication. In order to increase therapeutic efficacy and tumor selectivity, glioma selective expression of ICP34.5 in oncolytic HSV has been explored. As a candidate for glioma selective promoters, we examined a synthetic nestin promoter, which consists of the nestin enhancer and hsp68 minimum promoter. We first performed RT-PCR to examine nestin expression in various types of cultured cells. All the glioma cell lines tested (U251, U87dEGFR, Gli36d5, T98G, MGH238, U138) were confirmed to be positive for nestin expression. Astrocytes, on the other hand, were negative. We, therefore, constructed a novel HSV mutant, rQNestin34.5, which expresses ICP34.5 under control of the synthetic nestin promoter. In the experiments using cultured human glioma cell lines in vitro, rQNestin34.5 showed remarkable enhancements in both viral propagation and oncolysis compared to the ICP34.5-null virus (rHsvQ1). In four primary glioblastoma cells, rQNestin34.5 also showed remarkable enhancement in both viral propagation and oncolysis compared to control rHsvQ1. In normal human astrocytes, rQNestin34.5 showed equivalent toxicity to control rHsvQ1. We also performed Western blotting to examine the phosphorylation state of eIF2a. In glioma cell lines infected with rQNestin34.5, the level of phspho-eIF2a was lower than that of control rHsvQ1, confirming that the ICP34.5 is expressed selectively in glioma cells and resulted in a decrease of phospho-eIF2a level. This was responsible for its efficient propagation in glioma cells. We further characterized the anti-cancer efficacy of this new virus in vivo using an athymic mouse subcutaneous tumor model (U87dEGFR cells) and a brain tumor model (U87dEGFR cells). The rQNestin34.5 showed significantly more potent inhibition of tumor growth compared to control rHsvQ1. The mice with brain tumor treated by rQNestin34.5 survived longer than those treated by rHsvQ1.
The mother of ten whom life treated cruelly
Authors: Donald W MacCorquodale
Journal: BMJ (2003)

From BMJ USA 2003;June:334 

“Doctor, this is Mrs. Jones at the Social Service Department of El Paso County. I'm calling about Amelia Sanchez, who is on welfare. She has a youngster with a high fever, and I wonder if you'd go out and see the child.” She knew I would do it without sending a bill. I took off at once for an address on South Conejos Street, a kind of ghetto for Chicanos in Colorado Springs. Amelia's was the only home I ever visited in Colorado Springs that had an indoor “outhouse,” a pit privy in the basement.

Amelia was an obese Mexican American, a charming …
Rapamycin overcomes multidrug resistance (MDR) mediated by P-glycoprotein (Pgp), Multidrug Resistance Protein-1 (MRP-1), Breast Cancer Resistance Protein (BCRP) and Lung Resistance Protein (LRP) and synergizes with substrate drugs in MDR cells.
Authors: Attaphol Pawarode, Hans Minderman, Kieran L. O’loughlin, William R. Greco, Maria R. Baer
Journal: Cancer Research (2006)

5410   Mechanisms of drug resistance in acute myeloid leukemia (AML) and other malignancies include decreased cellular uptake and retention of substrate chemotherapy drugs due to overexpression of the ATP-binding cassette (ABC) proteins Pgp, MRP-1 and BCRP and decreased nuclear uptake and retention due to expression of the major vault protein LRP, as well as aberrant activation of cell survival and proliferation pathways, including PI3K/Akt. Rapamycin inhibits mTOR, a downstream effector of PI3K/Akt, has anti-proliferative effects in AML and is also known to block drug transport by Pgp by competitive inhibition. We studied its effects on drug transport and interactions with substrate chemotherapy drugs in cells overexpressing MRP-1, BCRP and LRP, as well as Pgp. Effects on drug uptake were studied by flow cytometry, cell survival in 96-hour cultures by the WST-1 assay and interactions of drug combinations by isobologram analysis. Exposure to rapamycin at 0.25μM, a clinically achievable concentration, for 3 hours increased cellular uptake of substrate chemotherapy drugs in cell lines overexpressing Pgp, MRP-1 and BCRP, and nuclear uptake in cell lines overexpressing LRP, but not in parental cells. Rapamycin dose-response curves were biphasic, with 20 to 40% decrease in cell survival following exposure to nM concentrations, and eradication of all cells following exposure to μM concentrations, suggesting different mechanisms of cell kill by rapamycin at different concentrations. Rapamycin IC 50 ’s were similar in multidrug resistant and parental cells, despite the fact that rapamycin is known to be a substrate for Pgp. Thus the data suggest that, in addition to modulating transport of other substrate drugs, rapamycin also modulates its own transport by Pgp, and likely also by MRP-1, BCRP and LRP. Concurrent treatment with rapamycin and mitoxantrone, a substrate for all four MDR proteins, resulted in a synergistic drug interaction in multidrug resistant cells. Thus rapamycin is a broad-spectrum MDR protein modulator and synergizes with MDR protein substrate drugs in multidrug resistant cells. Effects of rapamycin on drug transport should be considered along with effects on signal transduction in the design of combination regimens.
Serum 25-Hydroxyvitamin D Concentration and Risk for Major Clinical Disease Events in a Community-Based Population of Older Adults
Authors: Ian H. de Boer
Journal: Annals of Internal Medicine (2012)

Background: Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration. Objective: To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D. Design: Cohort study. Setting: The Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis. Participants: 1621 white older adults. Measurements: Serum 25-(OH)D concentration (using a high-performance liquid chromatography–tandem mass spectrometry assay that conforms to National Institute of Standards and Technology reference standards) and associations with time to a composite outcome of incident hip fracture, myocardial infarction, cancer, or death. Results: Over a median 11-year follow-up, the composite outcome occurred in 1018 participants (63%). Defining events included 137 hip fractures, 186 myocardial infarctions, 335 incidences of cancer, and 360 deaths. The association of low 25-(OH)D concentration with risk for the composite outcome varied by season (P = 0.057). A concentration lower than a season-specific Z score of −0.54 best discriminated risk for the composite outcome and was associated with a 24% higher risk in adjusted analyses (95% CI, 9% to 42%). Corresponding season-specific 25-(OH)D concentrations were 43, 50, 61, and 55 nmol/L (17, 20, 24, and 22 ng/mL) in winter, spring, summer, and autumn, respectively. Limitation: The observational study was restricted to white participants. Conclusion: Threshold concentrations of 25-(OH)D associated with increased risk for relevant clinical disease events center near 50 nmol/L (20 ng/mL). Season-specific targets for 25-(OH)D concentration may be more appropriate than static targets when evaluating health risk. Primary Funding Source: National Institutes of Health.
Science commentary: What does zinc do?
Authors: A. Berger
Journal: BMJ (2002)

Adequate zinc intake is critical for health. Zinc deficiency affects cells of the immune system. It causes a reduction in the number B lymphocytes and T lymphocytes (CD4 lymphocytes in particular) through increased apoptosis and also reduces their functional capacity. The functions of the macrophage, another key immunological cell that engulfs and destroys bacteria, are also compromised. The production and potency of several cytokines, the central messengers of the immune system, are also perturbed by zinc deficiency. Many of these changes occur even in the early stages of deficiency.

Zinc plays a part in the maintenance of epithelial and tissue integrity through promoting cell growth …
Abstract 3718: Adaptive drug escape of EML4-ALK lung cancer against targeted ALK inhibitor involving TGFβ2-mitochondrial priming
Authors: Lihong Yin, Wei Zhang, Ivy Shi, Yan Feng, Rakesh Bagai, Daniel Lindner, Patrick C. Ma
Journal: Cancer Research (2014)

Abstract Lung cancer is the second most common malignancy with the highest cancer-mortality rate. EML4-ALK chromosomal translocation is now known to represent a highly actionable unique molecular target in approximately 5% of non-small cell lung cancer (NSCLC) patients. The ALK tyrosine kinase inhibitor (TKI) crizotinib induces remarkably high response rates in molecularly-selected NSCLC patients harboring EML4-ALK driven tumors, and is being used in first-line therapy. Nonetheless, responsive tumors ultimately develop acquired drug resistance. We have recently investigated non-mutational mechanisms of tumor resistant escape emerging under early TKI treatment time-window. Our recent studies in EGFR-mutant NSCLC in early adaptive drug escape against EGFR TKI identified an autocrine upregulation of TGFβ2 within these survivor cells. Here, we found that TGFβ2 was elevated significantly in the EML4-ALK-driven H3122 cells undergoing early adaptive drug escape against ALK TKI (TAE684) at treatment day 14. Interestingly, we found that the augmented TGFβ signaling was specific to TGFβ2, but not TGFβ1 or TGFβ3. We also found correlative enhanced mitochondrial BCL-2/BCL-xL prosurvival signaling in the day 14 TKI surviving H3122 cells. The upregulated TGFβ2-BCL-2/BCL-xL prosurvival mitochondrial priming was further validated in H3122 xenografts by IHC. Exogenous TGFβ2 stimulation in vitro for 7 days induced a dose-dependent upregulated BCL-2 and BCL-xL expression. Inhibiting mitochondrial BCL-2/BCL-xL priming using dual BCL-2/BCL-xL inhibitor ABT-263 as BH3-mimetic led to significant reduction in early adaptive drug escape induced by ALK TKIs. Our study showed that EML4-ALK NSCLC could escape ALK TKI early in treatment through cell plasticity that involved TGFβ2-mitochondrial priming in an upregulated prosurvival state. We also found that the early adaptive drug-escaping cancer cells possessed inherently increased EMT-ness (upregulated vimentin, AXL, GAS6) and cancer stemness (upregulated OCT4, NANOG). These findings provide deeper insights into the process of drug resistance emergence and highlighted potential window-of-opportunities to therapeutically target early adaptive escape to eradicate targeted drug resistance and impact long term survival. Citation Format: Lihong Yin, Wei Zhang, Ivy Shi, Yan Feng, Rakesh Bagai, Daniel Lindner, Patrick C. Ma. Adaptive drug escape of EML4-ALK lung cancer against targeted ALK inhibitor involving TGFβ2-mitochondrial priming. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3718. doi:10.1158/1538-7445.AM2014-3718
Abstract P147: Healthcare Resource Utilization and Associated Costs in Type 2 Diabetes Mellitus Patients with Uncontrolled Glycemic Level or Blood Pressure
Authors: Chien-Chia Chuang, Edward Lee, Sharvari Bhurke, Sabyasachi Ghosh, Alie Tawah, Shih-Yin Chen
Journal: Circulation (2014)

Background: Poor glycemic and blood pressure (BP) control in patients with type 2 diabetes mellitus (T2DM) may lead to higher risk of complications with varying healthcare resource utilization (HRU). We hypothesize that poor glycemic and BP control are associated with higher HRU/costs. Methods: This study analyzed electronic health records from integrated delivery networks across the US between 2008 and 2012. Adult T2DM patients with at least two HbA1c and BP measures over a 12-month baseline period were selected. The end of this baseline period marks the index date. Patients were required to have an additional 12-month follow-up after the index date to evaluate HRU/costs. Uncontrolled HbA1c was defined as ≥ 1 HbA1c measure that was ≥7% during the baseline period. Uncontrolled BP was defined as ≥ 2 measures with systolic BP ≥ 130mmHg or diastolic BP ≥ 80mmHg during the baseline period. Descriptive analysis was conducted to compare HRU/costs across study cohorts. Unit cost approach was applied to derive total medical encounter costs. Logistic regression models were performed to assess the association between uncontrolled HbA1c/BP and HRU. Results: Of the 96,312 T2DM patients included in this study (mean age: 62.4 years; female: 51.5%), 55.9% had uncontrolled HbA1c (mean age: 61.2 years; female: 49.4%) and 74.6% had uncontrolled BP (mean age: 62.3 years; female: 52.8%). Patients with uncontrolled HbA1c had a higher proportion of hospitalizations (16.6% vs. 15.0%) , ER visits (21.0% vs. 18.3%), and higher total medical encounter costs ($4,168 vs. $3,773) than controlled patients, but lower utilization of outpatient visits (28.5% vs. 33.1%) and physician office visits (93.9% vs. 94.3%) (all p&lt;0.05). Patients with uncontrolled BP had a higher proportion of hospitalization (17.1% vs. 12.3%), ER visits (21.3% vs. 15.5%), and outpatient visits (33.3% vs. 22.5%) and higher total medical encounter costs ($4,236 vs. $3,282) than controlled patients, but lower utilization of physician office visits (93.6% vs. 95.4%) (all p&lt;0.05). In regression models, uncontrolled HbA1c was associated with greater odds of having any hospitalization (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.06–1.14) and ER visits (OR: 1.10; 95% CI: 1.07–1.14). Uncontrolled BP was also associated with greater odds of having any hospitalization (OR: 1.39; 95% CI: 1.33–1.45) and ER visits (OR: 1.37; 95% CI: 1.31–1.43). Conclusions: T2DM patients with uncontrolled HbA1c or BP had higher HRU in inpatient/ER settings and incurred higher costs. The findings highlight the clinical/economic significance of managing HbA1c and co-morbid hypertension among T2DM patients.