tbuckley/cabot-search huggingface dataset:
The Impact of Glycemic Control on Neonatal Outcome in Singleton Pregnancies Complicated by Gestational Diabetes
Authors: Víctor Hugo González-Quintero, Niki B. Istwan, Debbie J. Rhea, Lorna I. Rodriguez, Amanda Cotter, Jena Carter, Antoaneta Mueller, Gary J. Stanziano
Journal: Diabetes Care (2007)

To identify the impact of suboptimal blood glucose control on neonatal outcomes in women with gestational diabetes mellitus (GDM).Included were patients with singleton gestation enrolled in an outpatient GDM management program for at least 7 days who delivered at term. Blood glucose control was defined as an average fasting blood glucose of <95 mg/dl, 1-h postprandial of <140 mg/dl, or 2-h postprandial of <120 mg/dl. Data were compared between patients with optimal blood glucose control (n = 2,030) and those with suboptimal blood glucose control (n = 1,188). The primary study outcome was a composite variable consisting of macrosomia, large-for-gestational-age, hypoglycemia, jaundice, or stillbirth.Over one-third of infants in the poorly controlled group were positive for at least one factor comprising the composite variable compared with 24% from the controlled group (P < 0.001).Suboptimal glycemic control in women with GDM is associated with adverse neonatal outcome. Careful monitoring of blood glucose levels and initiation of appropriate treatment are essential in the care of women with GDM.
The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region.
Authors: S M Canfield, S L Morrison
Journal: The Journal of Experimental Medicine (1991)

A family of chimeric immunoglobulins (Igs) bearing the murine variable region directed against the hapten dansyl linked to human IgG1, -2, -3, and -4 has been characterized with respect to binding to the human high affinity Fc gamma receptor, Fc gamma RI. Chimeric IgG1 and -3 have the highest affinity association (Ka = 10(9) M-1), IgG4 is 10-fold reduced from this level, and IgG2 displays no detectable binding. A series of genetic manipulations was undertaken in which domains from the strongly binding subclass IgG3 were exchanged with domains from the nonbinding subclass IgG2. The subclass of the CH2 domain was found to be critical for determining IgG receptor affinity. In addition, the hinge region was found to modulate the affinity of the IgG for Fc gamma RI, possibly by determining accessibility of Fc gamma RI to the binding site on Fc. A series of amino acid substitutions were engineered into the CH2 domain of IgG3 and IgG4 at sites considered potentially important to Fc receptor binding based on homology comparisons of binding and nonbinding IgG subclasses. Characterization of these mutants has revealed the importance for Fc gamma RI association of two regions of the genetic CH2 domain separated in primary structure by nearly 100 residues. The first of these is the hinge-link or lower hinge regions, in which two residues, Leu (234) and Leu(235) in IgG1 and -3, are critical to high affinity binding. Substitution at either of these sites reduces the IgG association constant by 10-100-fold. The second region that appears to contribute to receptor binding is in a hinge-proximal bend between two beta strands within the CH2 domain, specifically, Pro(331) in IgG1 and -3. As a result of beta sheet formation within this domain, this residue lies within 11 A of the hinge-link region. Substitution at this site reduces the Fc receptor association constant by 10-fold.
Anterior and Posterior Hypopituitarism Associated with Sickle Cell Trait
Authors: ROBERT A. PASTURE
Journal: Annals of Internal Medicine (1969)

A 41-year-old negro man with fatigue, weight loss, decreased libido, impotence, polyuria, and polydipsia of 5 years' duration is described. Symptoms had begun 2 months after a prolonged, high-altitude flight. His prostate and testes were abnormally soft. Visual fields and chromosome analysis were normal. Testicular biopsy showed no spermatogenesis, with generalized tubular and interstitial atrophy. Hemoglobin electrophoresis showed A and S hemoglobins. Skull X rays showed suprasellar calcification, but carotid arteriograms were normal. Craniotomy showed no evidence of tumor or other lesions. The response of his low urinary steroid excretion to adrenocorticotrophic hormone and metyrapone (Metopirone®) indicated secondary hypoadrenalism. Plasma growth hormone did not increase with insulin-induced hypoglycemia. Thyroid function was at the lower limits of normal. The values for serum and urine osmolality after overnight fasting, saline infusion, vasopressin (Pitressin®) infusion, and prolonged water deprivation were diagnostic of pituitary diabetes insipidus. Review of the English literature showed two patients with sickle cell trait and pituitary infarction proved at autopsy. Since the nephropathy of sickle cell trait is vasopressin-resistant, vasopressin-responsive hyposthenuria in persons with S hemoglobin suggests pituitary involvement. A causal relationship between this patient's sickle trait and generalized hypopituitarism is suggested.
Transabdominal Angioaccess Catheter for Long-Term Hemodialysis
Authors: John B. Copley, Linda S. Bartram, Barbara J. Smith, Juan Sandoval, Mary K. James, Robert O. Hickman
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 February 1987Transabdominal Angioaccess Catheter for Long-Term HemodialysisLTC JOHN B. COPLEY, M.D., MC, JAMES A. HASBARGEN, M.D., MCLTC JOHN B. COPLEY, M.D., MCSearch for more papers by this author, JAMES A. HASBARGEN, M.D., MCSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-106-2-327_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the February 1984 issue (1) we reported the use of a transabdominal angioaccess catheter for long-term hemodialysis. We now wish to describe our further experience with this patient.The catheter was used successfully on a thrice-weekly hemodialysis schedule for 50 months until the patient died of a disorder unrelated to his dialytic therapy. During use of the catheter and despite the fact that the patient had an ileostomy, there were no instances of bacteremia or tunnel infection. Exit site infections did occur, but not at an excessive rate. All were treated successfully with oral antibiotics and...Reference1. COPLEYBARTRAMSMITHSANDOVALJAMESHICKMAN JLBJMR. Transabdominal angio-access catheter for long-term hemodialysis. Ann Intern Med. 1984;100:236-7. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The views of the authors do not represent the positions of the Department of the Army or the Department of Defense. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1987Volume 106, Issue 2Page: 327-327KeywordsAntibioticsBacteremiaCathetersIleostomy ePublished: 1 December 2008 Issue Published: 1 February 1987 PDF downloadLoading ...
Screening Colonoscopy in Very Elderly Patients
Authors: Otto S. Lin, Richard A. Kozarek, Drew B. Schembre, Kamran Ayub, Michael Gluck, Fred Drennan, Maw-Soan Soon, Linda Rabeneck
Journal: JAMA (2006)

Current guidelines do not include an upper age cutoff for colorectal cancer screening with colonoscopy. Although the prevalence of colonic neoplasia increases with age, life expectancy decreases. Thus, the benefit of screening colonoscopy in very elderly patients may be limited.To compare estimated life-years saved with screening colonoscopy in very elderly vs younger persons.Cross-sectional study conducted among 1244 asymptomatic individuals in 3 age groups (50-54 years [n = 1034], 75-79 years [n = 147], and > or =80 years [n = 63]) who underwent screening colonoscopy at a US teaching hospital and clinic.Prevalence of various types of colon neoplasia; estimated gain in life expectancy, calculated as life expectancy--(life expectancy during polyp lag time + life expectancy after colorectal cancer diagnosis); and comparison of mean gain in life expectancy across the 3 groups. Life expectancy and mortality data were derived from life tables, previous studies, and national databases.The prevalence of neoplasia was 13.8% in the 50- to 54-year-old group, 26.5% in the 75- to 79-year-old group, and 28.6% in the group aged 80 years or older. Despite higher prevalence of neoplasia in elderly patients, mean extension in life expectancy was much lower in the group aged 80 years or older than in the 50- to 54-year-old group (0.13 vs 0.85 years). In sensitivity analysis, with longer polyp lag times the mean extension in life expectancy decreased more in the elderly than in the younger patients; alternatively, if it was assumed that a smaller proportion of adenomas progress to colorectal cancer, the mean extension in life expectancy decreased less in the elderly than in the younger patients.Even though prevalence of neoplasia increases with age, screening colonoscopy in very elderly persons (aged > or =80 years) results in only 15% of the expected gain in life expectancy in younger patients. Screening colonoscopy in very elderly patients should be performed only after careful consideration of potential benefits, risks, and patient preferences.
Abstract 1229: E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis
Authors: Cen Zhang, Juan Liu, Xiaolong Wang, Ken H. Young, Wenwei Hu, Zhaohui Feng
Journal: Cancer Research (2015)

Abstract Tumor suppressor p53 plays a key role in maintaining genomic stability and preventing tumorigenesis through its regulation of cellular stress responses, including apoptosis, cell cycle arrest and senescence. To ensure its proper levels and functions in cells, p53 is tightly regulated mainly through post-translational modifications. Ubiquitination is the most important post-translational modification for p53. TRIM32 is a protein of the tripartite motif (TRIM) family. The proteins of TRIM family have been reported to be involved in different biological processes, including cell growth, differentiation, development, muscular physiology, innate immune response and cancer. However, like the majority of TRIM family proteins, the biological function of TRIM32 is not well-understood. Here, we identified TRIM32 as a novel p53 target gene and E3 ubiquitin ligase for p53. In response to stress, including ionizing radiation (IR) and chemotherapeutic agents (e.g. etoposide and 5-fluorouracil), p53 protein binds to the p53 responsive element in the promoter of the TRIM32 gene and transcriptionally induces the expression of TRIM32 in cells. In turn, TRIM32 protein interacts with p53 protein and promotes p53 degradation through ubiquitination to negatively regulate p53-mediated apoptosis, cell cycle arrest and senescence in response to stress. Thus, p53 and TRIM32 form a novel negative feedback loop in cells to regulate p53 protein levels and function. TRIM32 is frequently overexpressed in different types of human tumors, including lung, colorectal and liver cancers. TRIM32 overexpression promotes the oncogenic transformation of primary mouse embryonic fibroblasts in a largely p53-dependent manner. Furthermore, TRIM32 overexpression promotes tumorigenesis in mice through the down-regulation of p53 function. Taken together, our results demonstrated that as a novel p53 target and a novel negative regulator for p53, TRIM32 plays an important role in regulation of p53 and p53-mediated cellular stress responses. Furthermore, our results revealed that impairing p53 function is a novel mechanism for TRIM32 in tumorigenesis. Citation Format: Cen Zhang, Juan Liu, Xiaolong Wang, Ken H. Young, Wenwei Hu, Zhaohui Feng. E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1229. doi:10.1158/1538-7445.AM2015-1229
Targeted MET Inhibition in Castration-Resistant Prostate Cancer: A Randomized Phase II Study and Biomarker Analysis with Rilotumumab plus Mitoxantrone and Prednisone
Authors: Charles J. Ryan, Mark Rosenthal, Siobhan Ng, Joshi Alumkal, Joel Picus, Gwenaëlle Gravis, Karim Fizazi, Frédéric Forget, Jean-Pascal Machiels, Sandy Srinivas, Min Zhu, Rui Tang, Kelly S. Oliner, Yizhou Jiang, Elwyn Loh, Sarita Dubey, Winald R. Gerritsen
Journal: Clinical Cancer Research (2012)

To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients with castration-resistant prostate cancer (CRPC).This double-blinded phase II study randomized (1:1:1) patients with progressive, taxane-refractory CRPC to receive MP (12 mg/m(2) i.v. day 1, 5 mg twice a day orally days 1-21, respectively) plus 15 mg/kg rilotumumab, 7.5 mg/kg rilotumumab, or placebo (i.v. day 1) every 3 weeks. The primary endpoint was overall survival (OS).One hundred and forty-four patients were randomized. Median OS was 12.2 versus 11.1 months [HR, 1.10; 80% confidence interval (CI), 0.82-1.48] in the combined rilotumumab versus control arms. Median progression-free survival was 3.0 versus 2.9 months (HR, 1.02; 80% CI, 0.79-1.31). Treatment appeared well tolerated with peripheral edema (24% vs. 8%) being more common with rilotumumab. A trend toward unfavorable OS was observed in patients with high tumor MET expression regardless of treatment. Soluble MET levels increased in all treatment arms. Total HGF levels increased in the rilotumumab arms. Rilotumumab showed linear pharmacokinetics when co-administered with MP.Rilotumumab plus MP had manageable toxicities and showed no efficacy improvements in this estimation study. High tumor MET expression may identify patients with CRPC with poorer prognosis.
Experimental Examination of EFL and MATX Eukaryotic Horizontal Gene Transfers: Coexistence of Mutually Exclusive Transcripts Predates Functional Rescue
Authors: Jana Szabová, Petr Růžička, Zdeněk Verner, Vladimír Hampl, Julius Lukeš
Journal: Molecular Biology and Evolution (2011)

Many eukaryotic genes do not follow simple vertical inheritance. Elongation factor 1α (EF-1α) and methionine adenosyl transferase (MAT) are enzymes with complicated evolutionary histories and, interestingly, the two cases have several features in common. These essential enzymes occur as two relatively divergent paralogs (EF-1α/EFL, MAT/MATX) that have patchy distributions in eukaryotic lineages that are nearly mutually exclusive. To explain such distributions, we must invoke either multiple eukaryote-to-eukaryote horizontal gene transfers (HGTs) followed by functional replacement or presence of both paralogs in the common ancestor followed by long-term coexistence and differential losses in various eukaryotic lineages. To understand the evolution of these paralogs, we have performed in vivo experiments in Trypanosoma brucei addressing the consequences of long-term coexpression and functional replacement. In the first experiment of its kind, we have demonstrated that EF-1α and MAT can be simultaneously expressed with EFL and MATX, respectively, without affecting the growth of the flagellates. After the endogenous MAT or EF-1α was downregulated by RNA interference, MATX immediately substituted for its paralog, whereas EFL was not able to substitute for EF-1α, leading to mortality. We conclude that MATX is naturally capable of evolving patchy paralog distribution via HGTs and/or long- term coexpression and differential losses. The capability of EFL to spread by HGT is lower and so the patchy distribution of EF-1α/EFL paralogs was probably shaped mainly by deep paralogy followed by long-term coexistence and differential losses.
Predictive Value of Autoantibodies to IA-2 for Insulin Requirements in Japanese Subjects With Type 1 Diabetes
Authors: Tsuguhito Ota, Toshinari Takamura, Yukihiro Bando, Rika Usuda, Yukihiro Nagai
Journal: Diabetes Care (2003)

GAD autoantibodies (GADAs) are frequently detected before the onset of diabetes and indicate the development of insulin dependency (1). Phosphatase-like protein IA-2 antibodies (IA-2As) in combination with GADA have been shown to improve the positive predictive value for type 1 diabetes (2). However, the presence of IA-2A and its clinical usefulness in Japanese type 1 diabetic patients have not been fully determined. Here we report the significance of serum antibodies to IA-2A and GADA to predict the insulin requirement in Japanese patients with type 1 diabetes.

We studied 101 Japanese patients with type …
Inaccurate clinical nodal staging of non-small cell lung cancer: evidence from the MRC LU22 multicentre randomised trial
Authors: N. Navani, M. Nankivell, R. J. Stephens, M. K. B. Parmar, D. Gilligan, M. Nicolson, H. J. M. Groen, J. P. van Meerbeeck
Journal: Thorax (2010)

The clinical staging of non-small cell lung cancer (NSCLC) is of paramount importance. It determines prognosis and therapy, and inaccurate staging may result in inappropriate treatment. In particular, clinical staging that misses mediastinal metastases may result in the patient undergoing a futile thoracotomy. Conversely, accurately detecting mediastinal metastases preoperatively would allow consideration of concurrent chemoradiotherapy or neoadjuvant treatment.

Although sensitivity and specificity data of CT scanning, positron emission tomography (PET) and mediastinoscopy for the detection of mediastinal metastases exist, the impact on patient outcomes when combined with other standard staging techniques such as mediastinoscopy is limited. The MRC LU22 trial,1 which compared surgery alone with neoadjuvant chemotherapy followed by surgery, collected prospective data on clinical and pathological staging …
Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells.
Authors: R I Lechler, J R Batchelor
Journal: The Journal of Experimental Medicine (1982)

The immunogenicity of long-surviving, enhanced (AS X AUG)F1 renal allografts retransplanted into secondary AS recipients was restored by the injection of small numbers of donor strain dendritic cells derived from afferent lymph. Whereas 1 X 10(4) to 5 X 10(4) dendritic cells were able to trigger an acute rejection response, neither the passenger volume of donor strain blood nor 5 X 10(6) T or B lymphocytes were able to do so, thereby demonstrating more than a 100-fold difference in immunogenic potency. It is concluded that intrarenal dendritic cells provide the major immunogenic stimulus of a kidney allograft. These results suggest that the antigenic strength of major histocompatibility complex-incompatible tissue correlates with the content of donor strain dendritic cells. They also provide further evidence that antigens of the major histocompatibility complex behave like conventional antigens unless they are on the surface of allogeneic dendritic cells.
Estrogen Replacement Therapy and Breast Cancer Survival in a Large Screening Study
Authors: C. Schairer, M. Gail, C. Byrne, P. S. Rosenberg, S. R. Sturgeon, L. A. Brinton, R. N. Hoover
Journal: JNCI Journal of the National Cancer Institute (1999)

Hormone replacement therapy has been associated in some studies with reductions in breast cancer mortality among women who develop this disease. It is unclear whether this association reflects the biologic activity of the hormones or the earlier detection of tumors among hormone users. We examined breast cancer mortality among women who were diagnosed with axillary lymph node-negative and node-positive breast cancer according to the currency of estrogen use at diagnosis.Vital status through June 1995 was determined for 2614 patients with postmenopausal breast cancer diagnosed during the period from 1973 to January 1981. We estimated adjusted hazard-rate ratios (adjusting for tumor size, age, race, Quetelet [body mass] index, and number of positive lymph nodes in women with node-positive disease) and unadjusted cumulative probabilities of breast cancer death over time since diagnosis.Among patients with node-negative disease, rate ratios for breast cancer mortality associated with current use compared with nonuse at diagnosis were 0.5 (95% confidence interval [CI] = 0.3-0.8) until 144 months after diagnosis and 2.2 (95% CI = 0.9-5.2) thereafter. Mortality was not statistically significantly lower in past users. The cumulative probabilities of breast cancer mortality at the end of follow-up were 0.14, 0.14, and 0.09 in nonusers, past users, and current users, respectively. Among women with node-positive disease, the rate ratios associated with current and past use were both 0.5 until 48 months after diagnosis (95% CI = 0.3-0.8 for current users; 95% CI = 0.3-0.9 for past users) and were 1.1 (95% CI = 0.7-1.7) and 1.8 (95% CI = 1.2-2.7), respectively, thereafter. The cumulative probabilities of breast cancer mortality were 0.32, 0.39, and 0.27 in nonusers, past users, and current users, respectively.Patients with breast cancer who were using replacement estrogens at the time of diagnosis experienced reductions in breast cancer mortality, which waned with the time since diagnosis.
Some Quantitative Observations on Testicular Changes in BALB/c and C3H Mice implanted With Diethylstilbestrol
Authors: Michael B. Shimkin, Sarah Jane Smith, Peter M. Shimkin, Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1962)

Gross and histologic changes were studied in testes of strain BALB/cAn mice (susceptible to interstitial-cell tumors) and of C3Hf/An mice (resistant to interstitial-cell tumors) 3 to 180 days after subcutaneous implantation of a 5 mg pellet of 20 percent diethyistilbestrol in cholesterol. BALB/c mice showed no loss of testicular weight, preservation of spermatogenic elements, and gradual increase in the interstitial-cell volume. C3H mice showed severe loss of testicular weight, atrophy of the seminiferous tubules, and no increase in the interstitial tissue.