tbuckley/cabot-search huggingface dataset:
<i>p53</i> Codon 72 and <i>MDM2</i> SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome
Authors: Kaisa Sotamaa, Sandya Liyanarachchi, Jukka-Pekka Mecklin, Heikki Järvinen, Lauri A. Aaltonen, Päivi Peltomäki, Albert de la Chapelle
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The Arg/Pro polymorphism in codon 72 of p53 was recently associated with age of onset of colorectal cancer in Lynch syndrome. A novel polymorphism in the promoter region of MDM2 was associated with age of cancer onset in Li-Fraumeni syndrome. We studied the influence of both polymorphisms on age of onset in Lynch syndrome and of the p53 polymorphism also in sporadic colorectal cancer. Experimental Design: We genotyped p53 codon 72 in 193 individuals with Lynch syndrome mutations, 93 patients with sporadic microsatellite unstable colorectal cancer, and 93 patients with sporadic microsatellite stable colorectal cancer from Finland and 323 Finnish controls. We genotyped 30 colorectal cancer patients with Lynch syndrome mutations from Ohio and 118 U.S. controls. We genotyped SNP309 of MDM2 in the Lynch syndrome groups. We used χ2 test, Kaplan-Meier statistics, and Cox regression model to analyze the data. Results: Allele frequencies of both polymorphisms were similar in subjects and controls from both populations and showed Hardy-Weinberg equilibrium. Neither polymorphism was associated with age of colorectal cancer onset in any of the subject groups. Conclusions: This study failed to show any role of the p53 polymorphism on age of colorectal cancer onset in Lynch syndrome and sporadic colorectal cancer. The polymorphism in the MDM2 promoter had no affect on age of onset in Lynch syndrome. Accurate information about age of onset is important in clinical practice, especially in high-risk conditions. As association studies are vulnerable to biologically insignificant variation, both positive and negative findings need to be reported to enable unbiased assessment of the significance of putative risk variants.
Bone marrow origin of Ia-positive cells in the medulla rat thymus.
Authors: A N Barclay, G Mayrhofer
Journal: The Journal of Experimental Medicine (1981)

Irradiated rats were reconstituted with bone marrow from F1 hybrids. Ia antigen of donor-bone marrow origin was detected by an immunoperoxidase technique on cryostat sections and found predominantly in the medulla of rat thymus 2 wk after reconstitution. These Ia-bearing cells increased in number with time after reconstitution, but the Ia on the cortical epithelial cells remained of host origin. The nature of the bone marrow-derived cells and their implication for major histocompatibility complex restriction are discussed.
Risk Assessment Tool for Distant Recurrence After Platinum-Based Concurrent Chemoradiation in Patients With Locally Advanced Cervical Cancer: A Korean Gynecologic Oncology Group Study
Authors: Sokbom Kang, Byung-Ho Nam, Jeong-Yeol Park, Sang-Soo Seo, Sang-Young Ryu, Jae Weon Kim, Seung-Cheol Kim, Sang-Yoon Park, Joo-Hyun Nam
Journal: Journal of Clinical Oncology (2012)

Purpose Our study aimed to develop a model to predict distant recurrence in locally advanced cervical cancer, which can be used to select high-risk patients in enriched clinical trials. Patients and Methods Our study was a retrospective analysis of a multi-institutional cohort of patients treated between 2001 and 2009. According to the order of data submission, data from three institutions were allocated to a model development cohort (n = 434), and data from the remaining two institutions were allocated to an external validation cohort (n = 115). Patient information including [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) data and clinical outcome was modeled using competing risk regression analysis to predict 5-year cumulative incidence of distant recurrence. Results The competing risk analysis revealed that the following four parameters were significantly associated with distant recurrence: pelvic and para-aortic nodal positivity on FDG-PET, nonsquamous cell histology, and pretreatment serum squamous cell carcinoma antigen levels. This four-parameter model showed good discrimination and calibration, with a bootstrap-adjusted concordance index of 0.70. Also, the validation set showed good discrimination with a bootstrap-adjusted concordance index of 0.73. A user-friendly Web-based nomogram predicting 5-year probability of distant recurrence was developed. Conclusion We have developed a robust model to predict the risk of distant recurrence in patients with locally advanced cervical cancer. Further, we discussed how the selective enrichment of the patient population could facilitate clinical trials of systemic chemotherapy in locally advanced cervical cancer.
SYR-472, a novel once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial
Authors: Nobuya Inagaki, Hitoshi Onouchi, Hiroki Sano, Nobuo Funao, Shingo Kuroda, Kohei Kaku
Journal: The Lancet Diabetes & Endocrinology (2013)
Early Prediction of Antipsychotic Response in Schizophrenia
Authors: Christoph U Correll, Anil K Malhotra, Saurabh Kaushik, Marjorie McMeniman, John M Kane
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors' goal was to examine the predictive value of early symptom changes indicating response to antipsychotic medication in schizophrenia. METHOD: One hundred thirty-one acutely ill patients with schizophrenia received 4 weeks of fluphenazine treatment. Brief Psychiatric Rating Scale (BPRS) ratings were obtained at baseline and weekly. The authors examined the relationship between changes in BPRS total score and each factor score following 1 week of treatment and ultimate response status, defined as a reduction of 20% or more in total BPRS score. RESULTS: Every patient who displayed an improvement of less than 20% in BPRS total score and 95% of patients who displayed a reduction of less than 20% in BPRS thought disturbance factor score following 1 week of treatment were classified as nonresponders after 4 weeks of treatment. CONCLUSIONS: These data suggest that patients with minimal improvement in positive symptoms during the first week of treatment with a typical antipsychotic are unlikely to respond to a 4-week trial. These data require confirmation and extension to studies with second-generation antipsychotics.
Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial
Authors: David Cunningham, Istvan Lang, Eugenio Marcuello, Vito Lorusso, Janja Ocvirk, Dong Bok Shin, Derek Jonker, Stuart Osborne, Niko Andre, Daniel Waterkamp, Mark P Saunders
Journal: The Lancet Oncology (2013)
EVIDENCE FOR THE INSULIN-DIRECTED SPECIFICITY OF RABBIT ANTI-INSULIN SERUM 1
Authors: Edward R. Arquilla, Abram B. Stavitsky
Journal: Journal of Clinical Investigation (1956)

In the previous paper (2) a method was described for the immunological assay of microgram quantities of insulin. This method employed the reaction between rabbit antiserum to insulin and sheep erythrocytes conjugated with insulin. However, the applicability of the method to the measurement of insulin is obviously dependent upon the insulin-directed specificity of the antiserum which is employed in the assay. Therefore, the present experiments were designed to determine the specificity of rabbit antisera to crystalline beef insulin. In order to establish this specificity answers were sought to these questions: 1) To what extent will the insulin antisera react with contaminants that may be present in the crystalline beef insulin used for immunization? 2) Will these antisera react with proteins derived from beef plasma and other sources? 3) To what extent will the antisera to beef insulin react with insulin from other species? 4) Will the antisera interfere with the physiological action of insulin? Previous investigators have provided much information on some of these points. Lewis (3) and Barral and Roux (4) have shown that purified insulin is a different antigen from those in serum or crude extracts of pancreas. The immunological similarity of insulin prepared from several species has been demonstrated by Lewis (3) and also by Wasserman and Mirsky (5). Using the SchultzDale technique, Lewis (3) showed that guinea pigs can be sensitized with insulin from one species and shocked with insulin from another species. Wasserman and Mirsky (5) confirmed this in sensitization and complement fixation experiments. However, these experiments were qualitative in nature. Furthermore, the insulin preparations
Tubular Lesions Predict Renal Outcome in Antineutrophil Cytoplasmic Antibody–Associated Glomerulonephritis after Rituximab Therapy
Authors: Annelies E. Berden, Rachel B. Jones, Dianhdra D. Erasmus, Michael Walsh, Laure-Hélène Noël, Franco Ferrario, Rüdiger Waldherr, Jan A. Bruijn, David R. Jayne, Ingeborg M. Bajema
Journal: Journal of the American Society of Nephrology (2011)

Histopathological features in renal biopsies of patients with antineutrophil cytoplasmic antibody-associated vasculitis have predictive value for renal outcome in patients who receive standard treatment with cyclophosphamide and corticosteroids; however, whether the same holds true for rituximab-treated patients is unknown. We describe associations between renal histopathology and outcomes among patients treated with a rituximab-based regimen in the Randomized Trial of Rituximab versus Cyclophosphamide in ANCA-Associated Vasculitis trial. Two pathologists, blinded to clinical data, reviewed biopsies from 30 patients according to a standardized protocol that included assessment of T cell, B cell, and plasma cell infiltration, as well as scoring for tubulitis, interstitial inflammation, and glomerulitis. We did not observe associations between immunohistology scores and age, sex, estimated GFR at entry, or requirement for dialysis. However, tubulointerstitial inflammation was more severe among patients who had a positive test for the myeloperoxidase antineutrophil cytoplasmic antibody. In a multiple linear regression model, both CD3(+) T cell tubulitis and tubular atrophy independently associated with estimated GFR at 12 months. Tubular atrophy remained an independent predictor at 24 months (P<0.01). These results suggest that in addition to anti-B cell therapy, therapy directed at T cells may improve renal outcomes in antineutrophil cytoplasmic antibody-associated vasculitis.
The Winning Formulation: The Development of Paclitaxel in Pancreatic Cancer
Authors: Wen Wee Ma, Manuel Hidalgo
Journal: Clinical Cancer Research (2013)

Paclitaxel has wide application in anticancer therapy but was never considered an efficacious agent in pancreatic cancer. A review of the experience with the Cremaphor formulation hinted at paclitaxel's activity in pancreatic cancer, but the early development was hampered by significant toxicities such as neutropenia and infection at clinically tolerable doses. However, such efficacy was confirmed in the recently completed phase III Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), in which the addition of nab-paclitaxel to gemcitabine significantly improved the survival of patients with metastatic pancreatic cancer. Several other Cremaphor-free formulations of paclitaxel had also been evaluated in pancreatic cancer, and the reasons for the success of the albumin nanoparticulate are examined here. In the era of biologic and molecularly targeted agents, the success of nab-paclitaxel in recalcitrant pancreatic cancer is a timely reminder of the importance and relevance of pharmacology and novel drug delivery technology in the development of anticancer drugs.
Cost effectiveness of alternative planned places of birth in woman at low risk of complications: evidence from the Birthplace in England national prospective cohort study
Authors: E. Schroeder, S. Petrou, N. Patel, J. Hollowell, D. Puddicombe, M. Redshaw, P. Brocklehurst
Journal: BMJ (2012)

To estimate the cost effectiveness of alternative planned places of birth.Economic evaluation with individual level data from the Birthplace national prospective cohort study.142 of 147 trusts providing home birth services, 53 of 56 freestanding midwifery units, 43 of 51 alongside midwifery units, and a random sample of 36 of 180 obstetric units, stratified by unit size and geographical region, in England, over varying periods of time within the study period 1 April 2008 to 30 April 2010.64,538 women at low risk of complications before the onset of labour.Planned birth in four alternative settings: at home, in freestanding midwifery units, in alongside midwifery units, and in obstetric units.Incremental cost per adverse perinatal outcome avoided, adverse maternal morbidity avoided, and additional normal birth. The non-parametric bootstrap method was used to generate net monetary benefits and construct cost effectiveness acceptability curves at alternative thresholds for cost effectiveness.The total unadjusted mean costs were £1066, £1435, £1461, and £1631 for births planned at home, in freestanding midwifery units, in alongside midwifery units, and in obstetric units, respectively (equivalent to about €1274, $1701; €1715, $2290; €1747, $2332; and €1950, $2603). Overall, and for multiparous women, planned birth at home generated the greatest mean net benefit with a 100% probability of being the optimal setting across all thresholds of cost effectiveness when perinatal outcomes were considered. There was, however, an increased incidence of adverse perinatal outcome associated with planned birth at home in nulliparous low risk women, resulting in the probability of it being the most cost effective option at a cost effectiveness threshold of £20 000 declining to 0.63. With regards to maternal outcomes in nulliparous and multiparous women, planned birth at home generated the greatest mean net benefit with a 100% probability of being the optimal setting across all thresholds of cost effectiveness.For multiparous women at low risk of complications, planned birth at home was the most cost effective option. For nulliparous low risk women, planned birth at home is still likely to be the most cost effective option but is associated with an increase in adverse perinatal outcomes.
Insulin Resistance and Risk Factors for Cardiovascular Disease in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia
Authors: Kevin C. Oeffinger, Beverley Adams-Huet, Ronald G. Victor, Timothy S. Church, Peter G. Snell, Andrea L. Dunn, Debra A. Eshelman-Kent, Robert Ross, Peter M. Janiszewski, Alicia J. Turoff, Sandra Brooks, Gloria Lena Vega
Journal: Journal of Clinical Oncology (2009)

Purpose To determine the prevalence of insulin resistance and other risk factors for cardiovascular disease (CVD) in young adult survivors of childhood acute lymphoblastic leukemia (ALL). Patients and Methods In this cross-sectional evaluation of 118 survivors of childhood ALL (median age, 23.0 years; range, 18 to 37 years), insulin resistance was estimated using the homeostasis model for assessment of insulin resistance (HOMA-IR). Sex-specific comparisons were made with a cohort of 30- to 37-year-old individuals from the same region participating in the Dallas Heart Study (DHS, N = 782). ALL survivors were stratified by treatment with and without cranial radiotherapy (CRT). Results Female ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.6, 95% CI, 3.6 to 5.7; no CRT, mean 3.3, 95% CI, 2.8 to 3.8) in comparison with DHS women (mean 2.4, 95% CI, 2.2 to 2.7). Eighty percent of women treated with CRT had at least three of six CVD risk factors, and they were significantly more likely to have three or more risk factors compared with DHS women (odds ratio [OR], 5.96; 95% CI, 2.15 to 16.47). Male ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.0, 95% CI, 2.8 to 5.6; no CRT, mean 3.4, 95% CI, 2.9 to 3.9) in comparison with DHS men (mean 2.3, 95% CI, 2.1 to 2.6), but were not more likely to have multiple CVD risk factors. Conclusion ALL survivors had an increased prevalence of insulin resistance in comparison with a cohort of older individuals from the same community. Importantly, women treated with CRT seem to have an increased prevalence of multiple CVD risk factors, warranting close monitoring and risk-reducing strategies.
Emotion Recollected in Tranquility: Lessons Learned from the COX-2 Saga
Authors: Tilo Grosser, Ying Yu, Garret A. FitzGerald
Journal: Annual Review of Medicine (2010)

Nonsteroidal antinflammatory drugs (NSAIDs) inhibit prostaglandin formation by cyclooxygenases (COX) 1 and 2. NSAIDs selective for inhibition of COX-2 are less likely than traditional drugs to cause serious gastrointestinal adverse effects, but predispose to adverse cardiovascular events, such as heart failure, myocardial infarction, and stroke. Evidence from human pharmacology and genetics, genetically manipulated rodents, and other animal models and randomized trials indicates that this is consequent to suppression of COX-2-dependent cardioprotective prostagladins, particularly prostacyclin. Lessons drawn from how this saga unfolded are relevant to how we approach drug surveillance and regulation, integrate diversifed forms of information and might pursue a more personalized approach to drug efficacy and risk.
Survey on management of gout among Dutch rheumatologists
Authors: M K Reinders, T L T. A Jansen
Journal: Annals of the Rheumatic Diseases (2008)

Doherty et al recently published results of an international survey on the diagnosis and management of gout conducted among delegates attending EULAR 2006.1 In addition, we would like to present the results of a survey conducted among 242 Dutch rheumatologists in 2005.

We sent a survey to all Dutch rheumatologists and those in training, all of whom were member of the Dutch Society for Rheumatology. We presented a case of tophaceous gout and recurrent gouty arthritis where the serum urate level …
Gall bladder epithelium and cholesterol gall stones.
Authors: M E Caselli, E Morsiani, A Aleotti, V Alvisi
Journal: Gut (1990)

whole body insulin-mediated glucose uptake, evaluated by the euglycaemic clamp technique, tends to be lower in non-insulin dependent diabetic patients with gall stone disease than in diabetic patients without gall stone disease.Therefore, the risk of cholelithiasis could be in part due to defects in glucose metabolism.A high insulin concentration has been shown to be a good marker of insulin resistance,2 and we have shown the association between insulin resistance and lipid and lipoprotein abnormalities in patients with non-insulin dependent diabetes.'Therefore, the correlation of a high insulin concentration with lipid and lipoprotein abnormalities which we found in patients with gall stone disease' is expected.In any case, the possibility that a high insulin concentration is only a marker of impaired insulin-mediated glucose uptake in diabetic patients with gall stone disease is a novel finding which deserves further study.The relation of insulin resistance and gall stone disease is, however, of biological importance only if this association can be shown in non- diabetic subjects.
A FUNCTIONAL AND PATHOLOGICAL STUDY OF THE CHRONIC NEPHROPATHY INDUCED IN THE DOG BY URANIUM NITRATE
Authors: William deB. MacNider
Journal: The Journal of Experimental Medicine (1919)

1. Uranium nitrate is relatively more toxic for old animals than for young animals. 2. This relative toxicity is not only expressed in the old animals by a greater functional disturbance of the kidney, but is also shown by an inability on the part of these animals to repair the kidney injury and reestablish its functional capacity. 3. The intoxication in younger animals has been followed by a repair of the renal injury and a partial restoration of kidney function. 4. In these animals the processes of repair lead to the development of a chronic diffuse type of nephropathy in which the acid-base equilibrium of the blood may be maintained at the point of normality. In these animals renal functional tests indicate the presence of severe kidney injury.
Intra-articular yttrium 90 in rabbits. Comparison of behaviour of various radiocolloids in rabbits and in man.
Authors: J M Gumpel
Journal: Annals of the Rheumatic Diseases (1978)

Comparative studies of the retention of various yttrium 90 radiocolloids and of noncolloidal yttrium 90 chloride were performed in rabbits with arthritis induced in one knee. Two colloids, the citrate and resin forms, showed a statistically significant difference in retention between inflamed and normal knees, isotope being retained better in the normal knee. Marked differences were found in the handling of the various yttrium preparations in rabbits compared with previously reported results in man. These differences suggest that the rabbit with induced arthritis is not a suitable model in which to test retention of different radiocolloids before use in man.
Evolution of selenium utilization traits.
Authors: Héctor Romero, Yan Zhang, Vadim N Gladyshev, Gustavo Salinas
Journal: Genome biology (2005)

Abstract Background The essential trace element selenium is used in a wide variety of biological processes. Selenocysteine (Sec), the 21st amino acid, is co-translationally incorporated into a restricted set of proteins. It is encoded by an UGA codon with the help of tRNA Sec (SelC), Sec-specific elongation factor (SelB) and a cis -acting mRNA structure (SECIS element). In addition, Sec synthase (SelA) and selenophosphate synthetase (SelD) are involved in the biosynthesis of Sec on the tRNA Sec . Selenium is also found in the form of 2-selenouridine, a modified base present in the wobble position of certain tRNAs, whose synthesis is catalyzed by YbbB using selenophosphate as a precursor. Results We analyzed completely sequenced genomes for occurrence of the selA , B , C , D and ybbB genes. We found that selB and selC are gene signatures for the Sec-decoding trait. However, selD is also present in organisms that do not utilize Sec, and shows association with either selA , B , C and/or ybbB . Thus, selD defines the overall selenium utilization. A global species map of Sec-decoding and 2-selenouridine synthesis traits is provided based on the presence/absence pattern of selenium-utilization genes. The phylogenies of these genes were inferred and compared to organismal phylogenies, which identified horizontal gene transfer (HGT) events involving both traits. Conclusion These results provide evidence for the ancient origin of these traits, their independent maintenance, and a highly dynamic evolutionary process that can be explained as the result of speciation, differential gene loss and HGT. The latter demonstrated that the loss of these traits is not irreversible as previously thought.