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Biomedical subjects

S P Harris

Publications and source records attributed to S P Harris.

6 recordsLinked to original sources
PubMed2000

Polyamines decrease Ca(2+) sensitivity of tension and increase rates of activation in skinned cardiac myocytes.

Owing in part to their interactions with membrane proteins, polyamines (e.g., spermine, spermidine, and putrescine) have been identified as potential modulators of membrane excitability and Ca(2+) homeostasis in cardiac myocytes. To investigate whether polyamines also affect cardiac myofilament proteins, we assessed the effects of polyamines on contractility using rat myocytes and trabeculae that had been permeabilized with Triton X-100. Spermine, spermidine, and putrescine reversibly increased the [Ca(2+)] required for half-maximal tension (i.e., right-shifted tension pCa curves), with the following order of efficacy: spermine (+4) > spermidine (+3) > putrescine (+2). However, synthetic analogs that differed from spermine in charge distribution were not as effective as spermine in altering isometric tension. None of the polyamines had a significant effect on maximal tension, except at high concentrations. After flash photolysis of DM-Nitrophen (a caged Ca(2+) chelator), spermine accelerated the rate of tension development at low and intermediate but not high [Ca(2+)]. These results indicate that polyamines, especially spermine, interact with myofilament proteins to reduce apparent Ca(2+) binding affinity and speed cross-bridge cycling kinetics at submaximal [Ca(2+)].

Adenosine Triphosphate↗
PubMed1999

A mechanism for branchial acid excretion in marine fish: identification of multiple Na+/H+ antiporter (NHE) isoforms in gills of two seawater teleosts.

Both Na+/H+ exchange and the electrogenic extrusion of H+ via an H+-ATPase have been postulated to drive acid excretion across the branchial epithelium of fishes. While the H+-ATPase/Na+ channel system appears to be the predominant mechanism in some freshwater species, it may play a reduced role in seawater and brackish-water animals, where high external Na+ concentrations may thermodynamically favor Na+/H+ exchange driven by a Na+/H+ antiporter (NHE). In this study, we used molecular and immunological methods to assess the role of NHE isoforms in the branchial epithelium of the marine long-horned sculpin (Myoxocephalus octodecimspinosus) and the euryhaline killifish (Fundulus heteroclitus). Northern blot analysis of RNA probed with the human NHE-1 BamHI fragment suggested the presence of homologous gill NHE mRNA in sculpin. RT-PCR on gill RNA isolated from sculpin recovering from metabolic acidosis provided evidence for two distinct NHE isoforms; one with 76 % amino acid homology to mammalian NHE-2, and another 92 % homologous to trout erythrocytic beta-NHE. Killifish also have transcripts with 91 % homology to beta-NHE. Immunological detection using monoclonal antibodies for mammalian NHE-1 revealed a protein antigenically similar to this isoform in the gills of both species. Metabolic acidosis caused an approximately 30-fold decrease in expression of the NHE-1-like protein in sculpin. We speculate that beta-NHE in the gills plays the intracellular 'housekeeping' roles described for mammalian NHE-1. During systemic acidosis, apical gill NHE-2 (which is sensitive to external amiloride and low [Na+]) in parallel with a dramatic suppression of basolateral NHE-1 activity enhances net capdelta H+ transfers to the water.

Acidosis↗
PubMed1997

Epithelial localization of a reptilian Na+/H+ exchanger homologous to NHE-1.

Basolateral membranes of turtle (Pseudemys scripta) colon epithelial cells exhibit robust Na+/H+ exchange activity that can be activated by cell shrinkage and is blocked by amiloride [M. A. Post and D. C. Dawson. Am. J. Physiol. 262 Cell Physiol. 31):C1089-C1094, 1992]. The colonic epithelium actively absorbs Na+ and secretes K+ and HCO3-, but the role of basolateral Na+/H+ exchange, if any, in transepithelial transport is unknown. The current studies were undertaken to identify the gene product(s) responsible for the observed basolateral Na+/H+ exchange activity and to determine the cellular localization of the reptilian Na+/H+ exchange protein. We cloned and sequenced partial-length cDNAs that are likely to encode a reptilian homologue of the mammalian NHE-1 Na+/H+ exchanger isoform. The partial-length cDNAs were > 80% identical to mammalian NHE-1 homologues at the nucleotide level and recognized a transcript (approximately 5.8-6.0 kb) in RNA isolated from turtle colon, small intestine, stomach, kidney, urinary bladder, heart, and liver. In situ hybridization showed that mRNA encoding the reptile homologue of NHE-1 was expressed predominantly in the epithelial cells of these tissues. Immunofluorescent localization of the reptilian Na+/H+ exchanger protein using an antibody raised against a human NHE-1 fusion protein confirmed that protein expression paralleled abundant mRNA expression in epithelial cells of turtle stomach and colon, as well as in some nephron segments, and showed that the reptile NHE-1 homologue was localized exclusively to the basolateral membranes of these cells. The relatively high level of NHE-1 expression in epithelial cells, particularly those of the colon and stomach, suggests that NHE-1 function is important for the maintenance or regulation of ion transport processes that occur in these cell types.

Amino Acid Sequence↗
PubMed1994

Antibiotic-resistant Acinetobacter meningitis in neurosurgical patients.

Acinetobacter anitratus has emerged as one of the common pathogens responsible for postneurosurgical meningitis at the authors' institution. Seven patients with Acinetobacter meningitis were identified during the 4-year period of this study, five of whom acquired organisms susceptible only to imipenem and amikacin. Acinetobacter bacteremia occurred concomitantly in five patients. Despite late institution of therapy as a result either of organism misidentification on Gram stain or of unexpected acquisition of a highly resistant organism, the patients' outcome was favorable after the initiation of appropriate antibiotic therapy. Imipenem and amikacin, with or without intrathecal aminoglycosides, were effective in patients with resistant strains of Acinetobacter.

Acinetobacter Infections↗
PubMed1991

Plasma profiles of IL-6-like and TNF-like activities in brain-dead dogs.

The progression to somatic death after brain death is poorly understood. The role of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in this progression is unknown. TNF-like and IL-6-like plasma activities were assayed in a canine model of brain death in the presence and absence of a lipopolysaccharide (LPS) challenge (0.22 micrograms/kg). Bioassays for TNF-like and IL-6-like activities used WEHI and B9 cell lines, respectively. Brain death was induced by elevating and maintaining intracranial pressure above systolic arterial pressure. Anesthesia and the operative procedure did not cause a significant increase of either cytokine. Brain death (n = 8) itself did not cause a significant elevation of either cytokine compared with the sham brain-death control (n = 6) despite a significant decrease in mean arterial pressure (35 +/- 3 vs. 115 +/- 5 mmHg at 5 h). The brain-dead group treated with LPS (n = 6) responded with a significant elevation in IL-6-like and TNF-like activities compared with the vehicle-treated group. The rise of IL-6-like activity in response to LPS was greater in the brain-dead group than in the sham brain-dead group (n = 3); no significant difference was noted for the TNF-like response. We conclude that the progression to somatic death after brain death cannot be explained by increases in circulating TNF-like or IL-6-like activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗