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Biomedical subjects

L Seligman

Publications and source records attributed to L Seligman.

5 recordsLinked to original sources
PubMed1998

Haemodynamic and renal effects of felodipine in young and elderly subjects.

OBJECTIVE: To study the influence of age on renal and haemodynamic effects of the calcium antagonist felodipine. METHODS: Eight young (mean age 27 years) and eight elderly (mean age 75 years) healthy normotensive subjects were given felodipine intravenously for 120 min aiming at close to therapeutic plasma level concentration. Renal blood flow (RBF) and renal vascular resistance (RVR) was estimated from para-aminohippuric acid (PAH) clearance 51CrEDTA clearance was used to measure glomerular filtration rate (GFR) and used in the calculations of fractional excretion (FE) of electrolytes. Impedance cardiography was performed to assess stroke volume and for the calculation of cardiac output and ejection fraction. RESULTS: At the end of felodipine infusion, the concentration of felodipine was on average 10.0 nmol x l(-1) in young and 12.0 nmol x l(-1) in elderly subjects (NS). During felodipine infusion blood pressure (BP) decreased from 138/76 to 120/68 in elderly subjects. The BP in young subjects was 126/74 at basal and 125/70 after infusion of felodipine. The systemic and renal vascular resistance decreased to a similar extent in young and elderly subjects after felodipine infusion. Felodipine caused a decrease in systemic vascular resistance from 25.6 to 23.3 in elderly and from 23.8 to 21.8 in the young subjects. Mean values for RVR at baseline and during infusion of felodipine were significantly higher in the elderly (10.1-15.1) than in the young subjects (5.4-6.7). Felodipine reduced RVR by 10% in the young and by 12% in the elderly at the end of infusion. The young subjects had 31% higher GFR than the elderly subjects at the start of infusion. Felodipine infusion did not affect GFR. There were no effects on stroke volume and ejection fraction. An initial natriuretic effect was found after infusion of felodipine in the young subjects. The fractional excretion of all electrolytes tended to increase after both felodipine and placebo, more in the elderly than in the young subjects. CONCLUSION: The effects of felodipine on central and renal haemodynamics previously observed in young and middle-aged subjects also seem to exist in the elderly. Volume expansion seems to increase the excretion of electrolytes more in elderly than in young people, and therefore the effect of felodipine on natriuresis is more evident in young subjects.

Adult↗
PubMed1997

Peripheral muscle training in patients with clinical signs of heart failure.

The aim of the study was to evaluate, in a controlled setting, the effects of a 5-month dynamic peripheral training programme in patients with clinical signs of congestive heart failure with special reference to their anaerobic threshold, muscle function, heart rate variability and quality of life. Twenty-four randomized patients with clinical signs of heart failure in NYHA II-III entered the study. Training resulted in a significant (p = 0.01) change in the anaerobic threshold, the patients' ability to lift weights (p = 0.01) and performance of heel-lift (p = 0.01). The heart rate recorded during the training exercises decreased significantly (p = 0.04). There were no significant differences in peak oxygen uptake, isokinetic and isometric strength, HRV and quality of life except for three items in the control group. The results of this study indicate that peripheral training is beneficial for patients with clinical signs of congestive heart failure.

Aged↗
PubMed1995

Sequences determining the cytoplasmic localization of a chemoreceptor domain.

The Escherichia coli serine chemoreceptor (Tsr) is a protein with a simple topology consisting of two membrane-spanning sequences (TM1 and TM2) separating a large periplasmic domain from N-terminal and C-terminal cytoplasmic regions. We analyzed the contributions of several sequence elements to the cytoplasmic localization of the C-terminal domain by using chemoreceptor-alkaline phosphatase gene fusions. The principal findings were as follows. (i) The cytoplasmic localization of the C-terminal domain depended on TM2 but was quite tolerant of mutations partially deleting or introducing charged residues into the sequence. (ii) The basal level of C-terminal domain export was significantly higher in proteins with the wild-type periplasmic domain than in derivatives with a shortened periplasmic domain, suggesting that the large size of the wild-type domain promotes partial membrane misinsertion. (iii) The membrane insertion of deletion derivatives with a single spanning segment (TM1 or TM2) could be controlled by either an adjacent positively charged sequence or an adjacent amphipathic sequence. The results provide evidence that the generation of the Tsr membrane topology is an overdetermined process directed by an interplay of sequences promoting and opposing establishment of the normal structure.

Alkaline Phosphatase↗
PubMed1994

An amphipathic sequence determinant of membrane protein topology.

We developed a screen involving alkaline phosphatase gene fusions to identify mutations altering the membrane topology of a bacterial chemoreceptor (Escherichia coli Tsr). We identified three informative classes of mutations causing increased export of the protein's normally cytoplasmic carboxyl-terminal domain. The first class consisted of deletions eliminating all or most of the membrane-spanning sequence (TM2) immediately amino-terminal to the cytoplasmic domain. The second class consisted of mutations altering a highly amphipathic sequence at the beginning of the domain. The third class of mutation was a deletion of an upstream spanning sequence (TM1). The amphipathic sequence appears to be a novel determinant of membrane topology whose function is not due to its positive residue density. The amphipathic character of the sequence is relatively well-conserved in chemoreceptors and their relatives. Although deletions removing the amphipathic sequence or TM1 alone caused only partial carboxyl-terminal domain export, a double mutation removing both caused efficient export. This result suggests that the two sequences function independently to promote normal membrane insertion. The independent functioning of the two sequences may help ensure that Tsr insertion is normally a high fidelity process.

Amino Acid Sequence↗