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Biomedical subjects

M Bender

Publications and source records attributed to M Bender.

At least 37 records · Page 2Linked to original sources

Drosophila ecdysone receptor mutations reveal functional differences among receptor isoforms.

The steroid hormone ecdysone directs Drosophila metamorphosis via three heterodimeric receptors that differ according to which of three ecdysone receptor isoforms encoded by the EcR gene (EcR-A, EcR-B1, or EcR-B2) is activated by the orphan nuclear receptor USP. We have identified and molecularly mapped two classes of EcR mutations: those specific to EcR-B1 that uncouple metamorphosis, and embryonic-lethal mutations that map to common sequences encoding the DNA- and ligand-binding domains. In the larval salivary gland, loss of EcR-B1 results in loss of activation of ecdysone-induced genes. Comparable transgenic expression of EcR-B1, EcR-B2, and EcR-A in these mutant glands results, respectively, in full, partial, and no repair of that loss.

Animals↗

DHR3, an ecdysone-inducible early-late gene encoding a Drosophila nuclear receptor, is required for embryogenesis.

Response to the steroid hormone ecdysone in Drosophila is controlled by genetic regulatory hierarchies that include eight members of the nuclear receptor protein family. The DHR3 gene, located within the 46F early-late ecdysone-inducible chromosome puff, encodes an orphan nuclear receptor that recently has been shown to exert both positive and negative regulatory effects in the ecdysone-induced genetic hierarchies at metamorphosis. We used a reverse genetics approach to identify 11 DHR3 mutants from a pool of lethal mutations in the 46F region on the second chromosome. Two DHR3 mutations result in amino acid substitutions within the conserved DNA binding domain. Analysis of DHR3 mutants reveals that DHR3 function is required to complete embryogenesis. All DHR3 alleles examined result in nervous system defects in the embryo.

Amino Acid Sequence↗

D1 receptors mediate dopamine action in the fetal suprachiasmatic nuclei: studies of mice with targeted deletion of the D1 dopamine receptor gene.

Studies in rodents suggest the presence of a dopaminergic system that influences the function of a biological clock in the hypothalamic suprachiasmatic nuclei (SCN). To provide insights into mechanisms of dopamine action in the SCN, we studied transgenic mice that had either one allele (+¿-) or both alleles (-/-) of the D1 dopamine receptor gene deleted, along with normal (+/+) littermates. As expected, receptor labelling autoradiography studies using [125I]SCH 23982 showed a complete absence of D1 dopamine receptor binding sites in the SCN of -/- animals. When pregnant mice from +¿- x +¿- matings were injected with the D1 receptor agonist SKF 38393, or the dopamine reuptake blocker GBR 12909 at day 19 of gestation, c-fos mRNA expression was observed in the SCN of +/+ fetuses. In contrast, c-fos mRNA induction was not seen in -/- or +¿- litter mates. Injection of cocaine into pregnant dams also resulted in robust SCN c-fos mRNA expression in +/+ mice. Increases in SCN c-fos mRNA expression were also seen in +¿- and -/- mice suggesting that cocaine action in the SCN involves both D1 receptor-dependent and -independent mechanisms. Collectively, our studies of transgenic mice deficient in D1 receptors support the presence of a functional dopaminergic system in the fetal SCN. We also identify D1 receptors as the prominent transducer of dopamine action in the fetal SCN.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Gases in ice cores.

Air trapped in glacial ice offers a means of reconstructing variations in the concentrations of atmospheric gases over time scales ranging from anthropogenic (last 200 yr) to glacial/interglacial (hundreds of thousands of years). In this paper, we review the glaciological processes by which air is trapped in the ice and discuss processes that fractionate gases in ice cores relative to the contemporaneous atmosphere. We then summarize concentration-time records for CO2 and CH4 over the last 200 yr. Finally, we summarize concentration-time records for CO2 and CH4 during the last two glacial-interglacial cycles, and their relation to records of global climate change.

Journal Article↗

High-technology in home care. An overview of intravenous therapy.

The administration of i.v. medications in the home environment has proven to be a viable and highly desirable alternative to traditional hospitalization. Technology has been the driving force behind the safe transition of the more acutely ill patient from the hospital to the home. The variety of infusion pumps and venous access devices available provides a number of therapy choices, each tailored to the needs of the individual patient. Home infusion therapy allows for the integrity of the family to remain intact and provides the option for greater participation by the patient and caregiver in the development and implementation of the treatment plan. Most important, technology has led to the evolution of home infusion therapy as a high-quality, cost effective approach to care in a troubled health delivery system.

Catheterization, Central Venous↗

SIN-1 has no direct myocardial anti-ischemic action.

Anti-ischemic drugs may develop their cardiac activity via peripheral (reduction in preload and/or afterload) or cardiac (coronary vasculature, myocardial cell metabolism) effects. The aim of the study was to investigate whether SIN-1, the active metabolite of molsidomine, develops a direct myocardial anti-ischemic property. Three groups of seven patients each were treated with 0.4 mg SIN-1 administered via either the intracoronary (IC) or intravenous (IV) route, or with placebo in a double-blind randomized investigation. SIN-1 had no influence on either the ischemic parameters in the surface electrocardiogram (ECG) or the intracoronary ECG. There was also no change in peripheral or central hemodynamics or in the severity of angina following this low IC or IV dosage. There is no evidence of a direct myocardial anti-ischemic response of SIN-1. The well known anti-ischemic activity of SIN-1 or molsidomine has to be attributed to the proven peripheral and cardiac vascular responses.

Angioplasty, Balloon, Coronary↗

Personality in recovered depressed elderly.

Personality traits in euthymic elderly subjects with and without past histories of major depressive episodes were assessed using the Structured Clinical Interview for DSM-III-R and the Social Adjustment Scale-SR. Recovered depressed subjects were characterized by significantly more personality traits from DSM-III-R Clusters B and C than controls, and they exhibited differences in social adjustment, as well. Subjects who have recovered from depressive episodes may show significant differences in personality and social adjustment that might represent residua of past depression, a trait characteristic, or a risk factor for recurrence.

Aged↗

ICU family support group sessions: family members' perceived benefits.

The purpose of this research was to identify the relationship between attending an ICU family support group and the family's appraisal of stress, social support, and hope. In addition, the family members' perceived benefits of attending an ICU family support family support group session does not significantly change stress levels, feelings of hope, and social support. Analysis of data reconfirms that family members of critically ill patients have a tremendous need for information. Although findings revealed that the majority of the family members who attended the support session would recommend attending again, it is unclear whether the support session method is the most beneficial and cost-effective means to support families of critically ill patients.

Adaptation, Psychological↗

Human papillomavirus-16 DNA in a cutaneous invasive cancer.

A middle-aged man with a 20-year history of a warty lesion on his finger was diagnosed histologically as having an invasive carcinoma at that location. Molecular analysis of the lesion showed that human papillomavirus (HPV) DNA was present in this tumor. Under stringent hybridization conditions, only HPV-16 DNA, which is commonly associated with genital neoplasia or cutaneous bowenoid lesions, was detected. Two-dimensional gel electrophoresis revealed that various sections of the tumor contained mostly episomal viral DNA; but in one case, low levels of integrated HPV-16 DNA were detected as well.

Carcinoma, Squamous Cell↗

Identification and expression of the gap segmentation gene hunchback in Drosophila melanogaster.

Genetic analysis has shown that the gap segmentation gene hunchback (hb) is a member of the genetic hierarchy involved in pattern formation in Drosophila. To identify the hb gene, we have mapped the position of hb mutant breakpoints within a chromosomal walk of the 85A region by genomic Southern blots and determined the transcription pattern of DNA from the walk. We detect a single gene within the domain defined by breakpoint mapping. We conclude that we have identified the hunchback gene because three mutations that inactivate hb physically interrupt or delete this gene. Northern analysis shows that the hb gene gives rise to at least five overlapping transcripts ranging in length from 2.6 to 3.5 kilobases. S1 nuclease and primer extension experiments demonstrate that the gene employs two promoters and three polyadenylation sites. The two hb promoters have different temporal specificities. Transcripts arising from the upstream promoter are detected from 0-12 hours of embryogenesis as well as in adult female and male RNA preparations. Transcripts arising from the downstream promoter accumulate only from 0-6 hours of embryogenesis. During the syncytial blastoderm stage, transcripts from the hb gene accumulate over a broad anterior and a narrow posterior domain. This pattern sharpens during the late blastoderm/early gastrula stage to produce an embryo with two stripes of hybridization anterior and one stripe posterior. Later, hb transcripts are detected within the ventral hypoderm in extended germ band stage embryos.

Animals↗

Nitrofurans in the treatment of gastritis associated with Campylobacter pylori. The Gastrointestinal Physiology Working Group of Cayetano Heredia and The Johns Hopkins Universities.

We conducted a double-blind, placebo-controlled, randomized treatment study in Peruvian adults with antral gastritis associated with Campylobacter pylori. Patients received either 400 mg of furazolidone (n = 14), 400 mg of nitrofurantoin (n = 24), or a placebo (n = 31) for 14 days. Endoscopy was carried out at baseline, 1 day after ceasing therapy, and 6 wk after the end of treatment to verify colonization by C. pylori and determine the extent of gastric inflammation. Treatment with nitrofurantoin or furazolidone markedly reduced or, in some cases, cleared C. pylori from the antrum (p less than 0.0005 compared with placebo). Resolution of acute gastric inflammation, as evidenced by decreased polymorphonuclear leukocyte infiltration and regeneration of the mucus layer, paralleled the reduction in bacterial colonization (p less than 0.005 compared with placebo). A high percentage of patients experienced relapse (recolonization by C. pylori and return to pretreatment levels of gastritis) within 6 wk after cessation of treatment. Significant relief of dyspeptic symptoms was not evident during the study.

Adult↗