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Biomedical subjects

M Keller

Publications and source records attributed to M Keller.

At least 307 records · Page 17Linked to original sources

Bipolar II. Combine or keep separate?

Data on prior course, characteristics of index episode, and familial aggregation of patients with bipolar II disorder is discussed. The data supports the separation of this condition from both bipolar I and recurrent unipolar disorder.

Adult↗

Outcome in RDC schizo-affective depression: the importance of diagnostic subtyping.

A 2-year semiannual follow-up of 40 patients with RDC schizo-affective disorder, depressed type revealed poorer outcomes among those who were subtyped as chronic or mainly schizophrenic patients than among their counterparts with nonchronic or mainly affective schizo-affective depression. Outcomes for these latter groups, in turn, were no worse than those for patients with psychotic major depression. Among a variety of predictors entered into step-wise regression analyses, diagnosis was most important in predicting recovery overall and outcome at 6 months, while demographic variables, particularly sex, predicted outcome at 2 years.

Adult↗

Role of serotonin and noradrenaline in social dysfunction: a review of data on reboxetine and the Social Adaptation Self-evaluation Scale (SASS).

Social impairment is a common feature of depressive illness, often causing substantial and clinically meaningful dysfunction. Although the depressive symptoms and social impairment are linked, the naturalistic course and response to treatment of these two aspects of depression do not necessarily correlate. A variety of self-report and clinician-administered assessment scales which are specific for the measurement of social functioning and have good psychometric properties have been developed in the past 40 years. The most recent of these instruments is the Social Adaptation Self-evaluation Scale (SASS), a 21-item scale designed in 1989 to assess patient response to antidepressant treatment. SASS was used in two clinical trials comparing reboxetine, the new selective noradrenaline reuptake inhibitor (selective NRI), with fluoxetine. While no difference in efficacy was detectable by traditional assessments of symptoms, reboxetine proved to be significantly more effective than fluoxetine in improving social functioning in patients with depression. Reboxetine was also more effective than fluoxetine in rectifying social functioning in the subset of patients who remitted from an episode of major depression. Specifically, reboxetine improved patient motivation, energy and self-perception. These results indicate that antidepressant therapy can achieve more than symptom relief in depression. It is speculated that there may be a difference in the roles played by serotonin and noradrenaline in social functioning.

Antidepressive Agents↗

Lateral ankle instability and the Brostrom-Gould procedure.

Lateral ankle instability can present as either acute or chronic. Proper identification of the etiology is necessary to determine the proper treatment plan. The Brostrom-Gould procedure, when properly used, can provide adequate correction of the unstable ankle. A review of the procedure, its indications, and the results of 44 patients who underwent the procedure will be discussed.

Adult↗

Genetic analysis of the Rhizobium meliloti exoYFQ operon: ExoY is homologous to sugar transferases and ExoQ represents a transmembrane protein.

The nucleotide sequence of a 4.8-kb ClaI-EcoRI DNA fragment of megaplasmid 2 of Rhizobium meliloti Rm2011 involved in succinoglucan (EPS I) synthesis and nodule infection was determined. Four open reading frames (ORFs) were identified on this fragment. A mutational analysis revealed that these ORFs represent genes that were termed exoX, exoY, exoF, and exoQ. The locations of transposon insertions in these exo genes were determined at the nucleotide level. Plasmid integration mutagenesis revealed that the genes exoY, exoF, and exoQ are organized in an operon. The exoX gene running in opposite direction forms a monocistronic transcriptional unit. The exoX gene was shown to negatively influence the amount of EPS I synthesized. The exoY gene is coding for a membrane associated protein homologous to the C-terminal part of the Xanthomonas campestris glucosyltransferase GumD and the Salmonella typhimurium galactose transferase RfbP. ExoF, a probable periplasmatic protein, is nearly identical to the protein encoded by ORF1 of Rhizobium sp. strain NGR234. ExoQ is most probably a membrane associated protein as deduced by its hydrophobic structural features. All three genes of the exoYFQ operon were shown to be essential for succinoglucan synthesis and nodule infection.

Amino Acid Sequence↗

Analysis of the Rhizobium meliloti genes exoU, exoV, exoW, exoT, and exoI involved in exopolysaccharide biosynthesis and nodule invasion: exoU and exoW probably encode glucosyltransferases.

Sequence analysis of a 5.780-kb DNA fragment originating from megaplasmid 2 of Rhizobium meliloti 2011 involved in biosynthesis of exopolysaccharide I (EPS I) and invasion of alfalfa nodules revealed the presence of five exo genes designated exoU, exoV, exoW, exoT, and exoI. ExoT resembled transmembrane proteins, whereas ExoI displayed a characteristic signal peptide. Sequence comparisons with several polysaccharide-polymerizing enzymes of both prokaryotic and eukaryotic origin indicated that exoW and exoU encode glucosyltransferases. Moreover, ExoV displayed weak homologies to the ExoO, ExoA, ExoL, and ExoM proteins of R. meliloti, which are also discussed as glucosyltransferases. Using exo-lacZ transcription fusions in connection with plasmid integration mutagenesis, promoters were identified in front of exoI, exoT, exoW, exoV, and exoU.R. meliloti 2011 strains with mutations in exoT, exoW, exoV, and exoU produced no detectable EPS I and were unable to infect alfalfa nodules, whereas exoI mutants synthesized a reduced amount of EPS I and did infect alfalfa nodules.

Amino Acid Sequence↗

Molecular analysis of the Rhizobium meliloti mucR gene regulating the biosynthesis of the exopolysaccharides succinoglycan and galactoglucan.

The Rhizobium meliloti Tn5 mutant Rm3131, producing galactoglucan (EPS II) instead of succinoglycan (EPS I), was complemented by a 3.6-kb EcoRI-fragment of the Rhizobium meliloti genome. Sequencing of this fragment revealed six open reading frames (ORFs). The ORF found to be affected in the mutant Rm3131 codes for a putative protein of 15.7 kDa and forms a monocistronic transcriptional unit. Further genetic analysis revealed that the gene mutated in Rm3131 is identical to the previously described R. meliloti mucR gene (H. Zhan, S.B. Levery, C. C. Lee, and J.A. Leigh, 1989, Proc. Natl. Acad. Sci. USA 86:3055-3059). By hybridization it was shown that a mucR homologous gene is present in several rhizobacteria. The deduced amino acid sequence of MucR showed nearly 80% identity to the Agrobacterium tumefaciens Ros protein, a negative regulator of vir genes and necessary for succinoglycan production. MucR contains like Ros a putative zinc finger sequence of the C2H2 type. Transcriptional fusions of genes for EPS I and EPS II synthesis, the so-called exo and exp genes, with the marker gene lacZ were used to delineate the role of mucR for exo and exp gene expression. It was found that exp genes are negatively regulated by MucR on the transcriptional level, whereas a posttranscriptional regulation by MucR is assumed for exo genes. Furthermore, mucR is negatively regulating its own transcription.

Amino Acid Sequence↗

Persistence of depressive symptoms and cardiovascular death among patients with affective disorder.

OBJECTIVE: Studies of both community and clinical samples have associated depressive symptoms with risks for subsequent cardiovascular morbidity and mortality. Because the physiological mechanisms thought to underlie this link would be cumulative in their effects, the following analyses tested the prediction that risks for cardiovascular death would increase in proportion to the persistence of depressive symptoms in a long-term follow-up. METHODS: Baseline assessment was performed as patients sought treatment for major depressive disorder, mania, or schizo-affective disorder. Follow-up evaluations occurred semiannually for the next 5 years and annually thereafter. The 903 patients described, observed for a mean of 11.0 years (SD = 5.2 years), were divided into thirds according to the proportion of follow-up weeks in episodes of major depressive disorder, schizoaffective disorder, or intermittent depressive disorder. The resulting groups were then compared by cumulative risks of cardiovascular death. RESULTS: Patients whose depressive symptoms were the most persistent were no more likely to die of cardiovascular causes than were those with the fewest weeks ill. A regression analysis showed that older age and the presence of cardiovascular disease at baseline, but not the subsequent chronicity of depressive symptoms, predicted cardiovascular death. CONCLUSIONS: The physiological concomitants of depressive illness apparently do not promote cardiovascular mortality in a cumulative manner. Efforts should be directed toward identification of risk factors common to both lifetime depressive symptoms and cardiovascular morbidity.

Adult↗

Sensitive superoxide detection in vascular cells by the new chemiluminescence dye L-012.

The detection superoxide production in vascular cells is usually limited by a low sensitivity of available assays. We tested the applicability of the luminol derivate L-012 ¿8-amino-5-chloro-7-phenylpyridol¿3,4-dpyridazine-1,4(2H,3H)dione to measure superoxide production in cultured endothelial cells (human umbilical vein endothelial cells) and rat aortic segments. Following stimulation with the protein kinase stimulator phorbol 12-myristate 13-acetate (PMA, 1 microM) there was an 2.8-fold increase of L-012 chemiluminescence, whereas incubation with angiotensin II (100 nM) did not result in a measurable increase. Addition of vanadate (100 microM) considerably increased the chemiluminescence (up to 17-fold) after PMA and made possible the detection of an enhanced superoxide production after stimulation with angiotensin II (by 1.7-fold). This was due to a approximately 9-fold increase in signal intensity of L-012 in the presence of vanadate. Prolonged incubation with vanadate also led to a tyrosine phosphorylation-dependent increase in superoxide formation which was predominantly produced by an NAD(P)H oxidase. Short-term vanadate-enhanced L-012 chemiluminescence represents a highly sensitive assay making it possible to detect small changes of superoxide formation in intact vascular cells.

Coloring Agents↗

Changes in paraventricular vasopressin and oxytocin during the development of spontaneous hypertension.

The potential role of central neuroendocrine changes in the development of spontaneous hypertension was evaluated. The developmental changes in blood pressure and hypothalamic and plasma levels of vasopressin (AVP) and oxytocin (OT) were determined in groups of SHR and WKY animals from 3 to 24 weeks of age. Hypothalamic OT content was significantly lower in 3-, 6-, and 12-week-old SHR rats compared to age-matched WKY animals. Hypothalamic AVP content was not different at 3 weeks of age, but was lower in the SHRs at 6 and 12 weeks. To localize strain differences in AVP and OT, specific hypothalamic nuclei were removed from 300 microns frozen brain sections, and hormone content measured. Paraventricular AVP and OT content was lower in the SHRs which had increased blood pressure (6, 12, and 24 weeks of age) but not in the prehypertensive groups (3 weeks of age). Neuropeptide content was unchanged in the supraoptic nucleus or median eminence. Plasma levels of AVP were increased in the SHR, while OT was unchanged. Thus, genetic hypertension is associated with specific and localized changes in hypothalamic AVP and OT. The fact that the peptide deficit occurred in the paraventricular nucleus, a region thought to be involved in the control of autonomic function, may have important implications in terms of the pathogenesis of hypertension.

Animals↗

Repair of infected pseudoaneurysm with aortic arch replacement after orthotopic heart transplantation.

Arterial wall infections are rare after orthotopic heart transplantation. An infected pseudoaneurysm developed in a patient at the site of aortic cannulation 6 months after his transplant procedure. Debridement of the infected tissue necessitated removal of a major portion of the aortic arch and reconstruction with in situ placement of a synthetic polyester (Dacron) graft. In situ placement of grafts is a controversial form of treatment of arterial wall infections in other portions of the aorta. Because of the extensive nature of the infection and its site, no other option was available. This patient represents the first reported case of successful aortic arch replacement for an infected pseudoaneurysm after orthotopic heart transplantation.

Adult↗