tbuckley/cabot-search huggingface dataset:
Extensive gene rearrangements in the chloroplast DNAs of Chlamydomonas species featuring multiple dispersed repeats
Authors: E. Boudreau, M. Turmel
Journal: Molecular Biology and Evolution (1996)

We have constructed a physical and gene map for the chloroplast DNA (cpDNA) of the unicellular green alga Chlamydomonas gelatinosa, a close relative of Chlamydomonas reinhardtii. At 285 kb, the C. gelatinosa cpDNA is 89 kb larger than its C. reinhardtii counterpart. The alterations in the order of 77 genes on the cpDNAs of these green algae are attributable to nine inversions and one event of expansion/contraction of the inverted repeat. These rearrangements are much more extensive than those previously reported between the cpDNAs of the closely related Chlamydomonas moewusii and Chlamydomonas pitschmannii. Because the divergence level of the C. gelatinosa and C. reinhardtii chloroplast-encoded large subunit rRNA gene sequences is equivalent to that of the corresponding C. moewusii and C. pitschmannii sequences, our results may suggest that, in the same period of time, there have been more numerous rearrangements in the lineage comprising C. gelatinosa and C. reinhardtii than in the lineage comprising C. moewusii and C. pitschmannii. Alternatively, given that substitution rates in chloroplast genes are not necessarily uniform across lineages, the extensive rearrangements between the C. gelatinosa and C. reinhardtii cpDNAs may reflect a longer divergence period for this pair of Chlamydomonas species compared to that for the C. moewusii/C. pitschmannii pair. We have also found that, like its C. reinhardtii homologue but unlike its C. moewusii and C. pitschmannii counterparts, the C. gelatinosa cpDNA features a large number of dispersed repeated sequences that are readily detectable by Southern blot hybridization with homologous fragment probes. Assuming that the two pairs of closely related Chlamydomonas species diverged at about the same time, these data suggest that the susceptibility of Chlamydomonas cpDNAs to rearrangements is correlated with the abundance of repeated sequences. Preliminary characterization of a 345-bp C. gelatinosa cpDNA region containing a repeated sequence by both DNA sequencing and Southern blot analysis has revealed no sequence homology between this region and the cpDNAs of C. reinhardtii and other Chlamydomonas species.
Alterations in Insulin-like Growth Factor Binding Protein-1 and Sex Hormone Binding Globulin Levels in Type 1 Diabetic Adolescents With Microalbuminuria
Authors: László Barkai, Adrienn Tombácz
Journal: Diabetes Care (2001)

Puberty is considered a critical period for the development of microvascular complications of diabetes. Recently, we documented that more pronounced progression of albuminuria occurs during puberty than before or after puberty (1). This supports the concept that endocrine changes of puberty can lead to early initiation or acceleration of diabetic kidney damage. Therefore, we attempted to investigate the relationship between incipient nephropathy and pubertal hormones in adolescents with diabetes.

A total of 26 type 1 diabetic patients were selected for this study. Subjects were classified into two groups according to the presence of incipient nephropathy: patients with persistent microalbuminuria (5 boys and 5 girls, albumin excretion rate [AER] 20 μg/min three times within 3 months, age 14.4 ± 3.0 years, diabetes duration 6.2 ± 2.5 year, and mean HbA1c 8.4 ± 8.4%) and patients with normoalbuminuria (8 boys and …
Molecular mechanisms of acquired resistance to tyrosine kinase targeted therapy
Authors: J. Rafael Sierra, Virna Cepero, Silvia Giordano
Journal: Molecular Cancer (2010)

Abstract In recent years, tyrosine kinases (TKs) have been recognized as central players and regulators of cancer cell proliferation, apoptosis, and angiogenesis, and are therefore considered suitable potential targets for anti-cancer therapies. Several strategies for targeting TKs have been developed, the most successful being monoclonal antibodies and small molecule tyrosine kinase inhibitors. However, increasing evidence of acquired resistance to these drugs has been documented, and extensive preclinical studies are ongoing to try to understand the molecular mechanisms by which cancer cells are able to bypass their inhibitory activity. This review intends to present the most recently identified molecular mechanisms that mediate acquired resistance to tyrosine kinase inhibitors, identified through the use of in vitro models or the analysis of patient samples. The knowledge obtained from these studies will help to design better therapies that prevent and overcome resistance to treatment in cancer patients.
EULAR/EFORT recommendations for the diagnosis and initial management of patients with acute or recent onset swelling of the knee
Authors: R B M Landewé, K P Günther, C Lukas, J Braun, B Combe, P G Conaghan, K Dreinhöfer, D Fritschy, J Getty, H J L van der Heide, T K Kvien, K Machold, C Mihai, M Mosconi, R Nelissen, E Pascual, K Pavelka, M Pileckyte, W Puhl, L Punzi, W Rüther, M San-Julian, C Tudisco, R Westhovens, E Witso, D M F M van der Heijde
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of variation in diagnostic and therapeutic performance across disciplines, have found consensus in starting task forces aiming at achieving diagnostic and therapeutic uniformity, and have identified medical conditions with which representatives of both organisations will frequently be confronted in common clinical practice. The aim of the present work was to establish recommendations for the diagnosis and initial management of patients presenting with acute or recent onset swelling of the knee. Methods: The EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations were followed. Results: In all, 11 rheumatologists from 11 countries and 12 orthopaedic surgeons from 7 countries met twice under the leadership of 2 conveners, a clinical epidemiologist and a research fellow. After carefully defining the content and procedures of the task force, research questions were developed, a comprehensive literature search was performed and the results were presented to the entire committee. Subsequently, a set of 10 recommendations was formulated based on evidence from the literature if available, and after discussion and consensus building. Conclusions: This is the first combined interdisciplinary project of rheumatologists and orthopaedic surgeons, successfully aiming at achieving consensus in the diagnosis and initial management of patients presenting with acute or recent onset swelling of the knee.
Aberrant Methylation of the X-Linked Ribosomal S6 Kinase <i>RPS6KA6 (RSK4)</i> in Endometrial Cancers
Authors: Summer B. Dewdney, BJ Rimel, Premal H. Thaker, Dominic M Thompson, Amy Schmidt, Phyllis Huettner, David G. Mutch, Feng Gao, Paul J. Goodfellow
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Effective treatments for advanced endometrial cancer are lacking. Novel therapies that target specific pathways hold promise for better treatment outcomes with less toxicity. Mutation activation of the FGFR2/RAS/ERK pathway is important in endometrial tumorigenesis. RPS6KA6 (RSK4) is a putative tumor suppressor gene and is a target of the ERK signaling pathway. We explored the role of RSK4 in endometrial cancer. Experimental Design: We showed that RSK4 is expressed in normal endometrial tissue and is absent or much reduced in endometrial cancer. On the basis of previous reports on methylation in other cancers, we hypothesized that the absence of RSK4 transcript is associated with epigenetic silencing rather than mutation. We determined the methylation and expression status of RSK4 in primary endometrial cancers and cell lines and the effects of treatment with a demethylating agent. The relationship between RSK4 methylation and clinicopathologic features was assessed. Results: RSK4 is frequently hypermethylated in endometrial cancer cells lines and in primary endometrial cancer compared with normal endometrial tissue. RSK4 methylation was significantly associated with tumor grade, with higher grade tumors having lower levels of methylation (P = 0.03). RSK4 methylation levels were not associated with other clinical variables. We did find that RSK4 methylation was significantly correlated with expression in primary endometrial tumors and in cell lines. Reactivation of RSK4 by 5-azacytidine was successfully performed showing 8- to more than 1,200-fold increases in transcript levels. Conclusion: RSK4 appears to be epigenetically silenced in endometrial cancer as evidenced by hypermethylation. Its role as a suppressor in endometrial cancer, however, remains uncertain. Clin Cancer Res; 17(8); 2120–9. ©2011 AACR.
Spontaneous and Amino Acid-Stimulated Glucagon Secretion in the Immediate Postnatal Period
Authors: Mark A. Sperling, Paul V. Delamater, Dale Phelps, Robert H. Fiser, William Oh, Delbert A. Fisher
Journal: Journal of Clinical Investigation (1974)

The extent and significance of spontaneous glucagon secretion in the immediate postnatal period were investigated in groups of normal infants studied cross-sectionally and longitudinally. Arginine-and alanine-stimulated glucagon secretion was also studied. Plasma glucagon concentrations were correlated with prevailing glucose and insulin concentrations. The characteristic fall in blood glucose, reaching a nadir within hours of birth, was associated with a significant increase in glucagon concentration. Despite persistence of relative glucopenia, glucagon did not change appreciably between 2 and 24 h of life. A further significant elevation in glucagon concentration occurred from day 1 to day 3 of life associated with a return of glucose to euglycemic levels. In contrast to the sluggishness of pancreatic glucagon release, glucagon-like immunoreactivity rose markedly to mean levels of approximately 2,000 pg/ml after introduction of formula feeding. No significant changes in insulin levels were observed in these studies. Arginine infusion via an umbilical vein catheter into six infants within 6 h of birth elicited a brisk, almost threefold increment in glucagon concentration (from 339+/-85 to 940+/-254 pg/ml) in blood obtained from, or close to, the portal circulation. Bolus injection of alanine (1 mmol/kg) into a peripheral vein to six infants resulted in significant increments in glucagon (mean maximal, 128 pg/ml) as well as glucose and insulin. The observations suggest that spontaneous glucagon secretion may be an important factor in neonatal glucose homeostasis. Secretion seems more brisk in response to amino acid stimulation than to a falling glucose concentration.
In Vivo Ventricular Gene Delivery of a β-Adrenergic Receptor Kinase Inhibitor to the Failing Heart Reverses Cardiac Dysfunction
Authors: Ashish S. Shah, David C. White, Sitaram Emani, Alan P. Kypson, R. Eric Lilly, Katrina Wilson, Donald D. Glower, Robert J. Lefkowitz, Walter J. Koch
Journal: Circulation (2001)

Background —Genetic manipulation to reverse molecular abnormalities associated with dysfunctional myocardium may provide novel treatment. This study aimed to determine the feasibility and functional consequences of in vivo β-adrenergic receptor kinase (βARK1) inhibition in a model of chronic left ventricular (LV) dysfunction after myocardial infarction (MI). Methods and Results —Rabbits underwent ligation of the left circumflex (LCx) marginal artery and implantation of sonomicrometric crystals. Baseline cardiac physiology was studied 3 weeks after MI; 5×10 11 viral particles of adenovirus was percutaneously delivered through the LCx. Animals received transgenes encoding a peptide inhibitor of βARK1 (Adeno-βARKct) or an empty virus (EV) as control. One week after gene delivery, global LV and regional systolic function were measured again to assess gene treatment. Adeno-βARKct delivery to the failing heart through the LCx resulted in chamber-specific expression of the βARKct. Baseline in vivo LV systolic performance was improved in Adeno-βARKct–treated animals compared with their individual pre–gene delivery values and compared with EV-treated rabbits. Total β-AR density and βARK1 levels were unchanged between treatment groups; however, β-AR–stimulated adenylyl cyclase activity in the LV was significantly higher in Adeno-βARKct–treated rabbits compared with EV-treated animals. Conclusions —In vivo delivery of Adeno-βARKct is feasible in the infarcted/failing heart by coronary catheterization; expression of βARKct results in marked reversal of ventricular dysfunction. Thus, inhibition of βARK1 provides a novel treatment strategy for improving the cardiac performance of the post-MI heart.
Phase III Trial of Paclitaxel at Two Dose Levels, the Higher Dose Accompanied by Filgrastim at Two Dose Levels in Platinum-Pretreated Epithelial Ovarian Cancer: An Intergroup Study
Authors: George A. Omura, Mark F. Brady, Katherine Y. Look, Hervy E. Averette, James E. Delmore, Harry J. Long, Scott Wadler, Gregory Spiegel, Susan G. Arbuck
Journal: Journal of Clinical Oncology (2003)

To determine if increasing the dose of paclitaxel increases the probability of clinical response, progression-free survival, or overall survival in women who have persistent or recurrent ovarian cancer, and whether doubling the dose of prophylactic filgrastim accompanying the higher paclitaxel dose decreases the frequency of neutropenic fever.Consenting patients with persistent, recurrent, or progressing ovarian cancer, despite first-line platinum therapy (but no prior taxane), were randomly assigned to paclitaxel 135 mg/m2, 175 mg/m2, or 250 mg/m2 over 24 hours every 3 weeks. Patients receiving paclitaxel 250 mg/m2 were also randomly assigned to 5 or 10 microg/kg of filgrastim per day subcutaneously.Accession to the paclitaxel 135-mg/m2 arm was closed early. Among the 271 patients on the other regimens with measurable disease, partial and complete response on paclitaxel 250 mg/m2 (36%) was significantly higher than on 175 mg/m2 (27%, P =.027). This difference was more evident among patients who never responded to prior platinum. However, progression-free and overall survival results were similar. The median durations of overall survival were 13.1 and 12.3 months for paclitaxel 175 mg/m2 and 250 mg/m2, respectively. Thrombocytopenia, neuropathy, and myalgia were greater with paclitaxel 250 mg/m2 (P <.05). The incidence of neutropenic fever after the first cycle of paclitaxel 250 mg/m2 was 19% and 18% on the 5-microg/kg and 10-microg/kg filgrastim dose, respectively (22% for paclitaxel 175 mg/m2 without filgrastim).Paclitaxel exhibits a dose effect with regard to response rate, but there is more toxicity and no survival benefit to justify paclitaxel 250 mg/m2 plus filgrastim. Doubling the filgrastim dose from 5 to 10 microg/kg did not reduce the probability of neutropenic fever after high-dose paclitaxel.
Prostate Cancer: Evolution or Revolution?
Authors: Eric J. Small, Johann Sebastian de Bono
Journal: Journal of Clinical Oncology (2011)

In this issue of Journal of Clinical Oncology, we present a special series on prostate cancer that illustrates how our understanding of the biology and therapy of this disease has changed over the last few years. This series comes on the heels of the 2011 Genitourinary Cancers Symposium (held February 17 to 19, 2011, in Orlando, FL), jointly sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic and Radiation Oncology, and the Society of Urologic Oncology. It is instructive to consider how the field has evolved, as articulated in the review articles in this issue, compared with the state of the art described in a special edition of the Journal published shortly after the first Prostate Cancer Symposium in 2005.
High-dose ifosfamide plus adriamycin in the treatment of adult advanced soft tissue sarcomas: Is it feasible?
Authors: T. De Pas, F. De Braud, L. Orlando, F. Nolè, E. Munzone, M.G. Zampino, N. Fazio, M.S. Aapro, A. Goldhirsch
Journal: Annals of Oncology (1998)
Recommendations for Follow-up Care of Individuals With an Inherited Predisposition to Cancer
Authors: Wylie Burke, Gloria Petersen, Patrick M Lynch, Jeffrey Botkin, Mary Daly, Judy Garber, Mary Jo Ellis Kahn, Anne McTiernan, Kenneth Offit, Elizabeth Thomson, Claudette Varricchio
Journal: JAMA (1997)

<h3>Objective.</h3> —To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). <h3>Participants.</h3> —A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). <h3>Evidence.</h3> —Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "colon cancer," and "screening" in combination with "cancer family" and "HNPCC." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. <h3>Consensus Process.</h3> —The task force developed recommendations through discussions over a 14-month period. <h3>Conclusions.</h3> —Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations. Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit. No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.
HLA-DR-DQ Haplotype in Rapid-Onset Type 1 Diabetes in Japanese
Authors: Tomoatsu Nakamura, Shoichiro Nagasaka, Ikuyo Kusaka, Toshimitsu Yatagai, Jianmei Yang, Shun Ishibashi
Journal: Diabetes Care (2003)

Results from a population-based survey Our objective was to evaluate the diagnostic proficiency of the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP)-III definitions (1,2) for the metabolic syndrome in a Mexican nationwide, population-based survey.Details of the sampling procedures have been previously described (3).The population was composed of 2,158 men and women aged 20 -69 years sampled after a 9-to 12-h fasting period.For the WHO criteria, insulin resistance was diagnosed if a nondiabetic case had fasting insulin concentrations Ն126 pmol/l (21 U/ml) (Ͼ75th percentile in Mexican adults).The ageadjusted prevalence was 13.61% for the WHO criteria (n ϭ 268) and 26.6% for the NCEP-III definition (n ϭ 574).After excluding patients with diabetes, the prevalence was 9.2 and 21.4%, respectively.The agreement between the definitions was assessed in 1,969 subjects; 189 cases were eliminated due to the lack of a urine sample.The number of abnormal cases was lower using the WHO criteria.Only 237 of the 545 subjects (43.4%) who fulfilled the NCEP criteria were diagnosed as affected using the WHO definition.Just 16 of 253 cases (6.3%) detected by the WHO definition did not fulfill the NCEP definition.The agreement between the criteria was moderate ( ϭ 0.507).On the other hand, the subjects diagnosed using the WHO recommendations had a worse profile than the cases detected by the NCEP-III definition only-they had a higher BMI and higher non-HDL cholesterol, triglyceride, and glucose concentrations.The demonstration of insulin resistance among the nondiabetic population caused the lack of agreement in 202 of the 242 cases that fulfilled the NCEP definition but failed the WHO criteria.Other reasons for disparity were the higher thresholds used by the WHO criteria; these differences explained the lack of agreement in 66 of the 152 cases with diabetes.In conclusion, the prevalence of the metabolic syndrome is influenced by the selection of the diagnostic criteria.The WHO criteria identified a lower number of cases than the NCEP-III definition.These differences were explained mainly by the inclusion of abnormally high insulin concentrations as a diagnostic criterion.However, the presence of insulin resistance may help to identify patients more severely affected (4).
Mechanism of 5-HT contraction in isolated bovine ventricular coronary arteries. Evidence for transient receptor-operated calcium influx channels.
Authors: P H Ratz, S F Flaim
Journal: Circulation Research (1984)

The effect of serotonin on isometric tension and transmembrane calcium influx was investigated in rings cut from branches of male bovine circumflex and left anterior descending coronary arteries. Responses were compared to those produced by potassium chloride, and to the serotonin contraction produced in rabbit thoracic aorta. Serotonin in bovine ventricular coronary arteries produced a strong, transient contraction, even at a maximum concentration. Contraction did not decline because of serotonin degradation in the bathing medium. The ability of serotonin to contract bovine ventricular coronary arteries was largely preserved when rings were exposed to a calcium-free medium. When calcium was replaced in the medium, both tension (T) and calcium influx (C, 45Ca) were increased above control only transiently by serotonin (3 minutes post-serotonin: T = 49.0 +/- 13.3 mg/mg, C = 27.33 +/- 1.8 mumol/kg, compared with control T = -4.8 +/- 1.5, C = 19.7 +/- 1.4; 30 minutes post-serotonin: T = -17.3 +/- 2.1, C = 19.3 +/- 1.1, compared with control T = -19.6 +/- 4.1, C = 18.1 +/- 1.4). Potassium chloride-stimulated increases in tension and calcium influx in bovine ventricular coronary arteries and a maximum serotonin contraction in rabbit thoracic aorta were not transient, but were sustained 30 minutes via a mechanism that appeared to be dependent on the influx of extracellular calcium. We suggest that the transient nature of the serotonin contraction in bovine ventricular coronary arteries was the result of a time-dependent decline in both calcium release from intracellular stores and calcium influx through serotonin receptor-operated calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
A case of gnathostomiasis in a European traveller returning from Mexico.
Authors: P. Del Giudice, P. Dellamonica, J. Durant, V. Rahelinrina, M.P. Grobusch, K. Janitschke, A. Dahan-Guedj, Y. Le Fichoux
Journal: British Journal of Dermatology (2001)

Hundreds of human cases of gnathostomiasis have recently been reported from Mexico, where the disease is becoming a public health problem. We report a case of gnathostomiasis in a French tourist returning from Mexico. Tourists travelling in endemic countries are at risk of gnathostomiasis and should be advised about the risks of eating raw fish as a suspected source of infection.