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Biomedical subjects

S Lynn

Publications and source records attributed to S Lynn.

At least 37 records · Page 2Linked to original sources
PubMed1995

Isolation and partial cloning of ryanodine-sensitive Ca2+ release channel protein isoforms from human myometrial smooth muscle.

Partial cDNAs of the ryanodine receptor were cloned using PCR analysis from reverse transcribed total and mRNA, extracted from freshly isolated pregnant, non-pregnant, and cultured human myometrial smooth muscle. The identity of these clones was confirmed by nucleotide sequencing of the fragments and indicate the expression of both the skeletal and brain ryanodine receptor isoforms in these preparations. In freshly isolated non-pregnant myometrial tissue, membrane fractions displaying specific [3H]ryanodine binding activities were isolated using density gradient centrifugation. SDS-PAGE of the sucrose gradient fractions indicated the specific comigration of a polypeptide with a molecular mass of approximately 544 kDa with the ryanodine binding activity.

Amino Acid Sequence↗
PubMed1995

Basic properties of a novel ryanodine-sensitive, caffeine-insensitive calcium-induced calcium release mechanism in permeabilised human vascular smooth muscle cells.

The efflux of 45Ca2+ from preloaded intracellular stores of saponin-permeabilised human uterine artery smooth muscle cultured cells was used to study the mechanisms underlying Ca2+ release from the sarcoplasmic reticulum (SR). The present paper demonstrates directly a functional Ca2+ release mechanism that is dependent on an increase in free Ca2+ (100 nM-30 microM) and is completely inhibited by 20 microM Ruthenium red. The amount of Ca2+ released at 30 microM free Ca2+ was reduced by approximately 50% compared to the release at 10 microM. This Ca(2+)-induced Ca2+ release (CICR) mechanism was not sensitive to caffeine. Exposure of cells to low free Ca(2+)-containing solutions (10 nM) indicated that a component of the CICR mechanism may be functional at basal free Ca2+ levels of 100 nM. Application of ryanodine (0.1-100 microM) induced 45Ca2+ efflux from the sarcoplasmic reticulum and this release was also inhibited by 20 microM Ruthenium red.

Adult↗
PubMed1995

Randomized trial of the canalith repositioning procedure.

Thirty-six subjects with confirmed, unilateral benign paroxysmal positioning vertigo of at least 2 months' duration were randomly assigned to one of two treatment groups. After complete informational counseling and explanation of the posttreatment instructions, subjects were randomly assigned to receive either Epley's canalith repositioning procedure or a placebo maneuver. All subjects completed a daily diary for 1 month to document any dizzy spells and their adherence to the posttreatment instructions. Follow-up Dix-Hallpike testing was performed after 1 month by an audiologist who was blinded to the patient's treatment group status. Analysis of Dix-Hallpike results confirmed that those who received the canalith repositioning procedure had significantly more negative responses (88.9%) than did those in the placebo group (26.7%).

Adult↗
PubMed1994

Identification of two aspartates and a glutamate essential for the activity of endo-beta-N-acetylglucosaminidase H from Streptomyces plicatus.

In order to identify groups essential for the activity of endo-beta-N-acetylglucosaminidase H (Endo H), all 8 glutamate residues, all 19 aspartates, and both tryptophans were individually substituted with glutamines, asparagines, and phenylalanines, respectively, by oligonucleotide site-directed mutagenesis. Only variants D170N, D172N, and E174Q were found to have specific activities significantly less than wild-type Endo H. Another variant, D173N, did not produce detectable amounts of protein. Wild-type enzyme was found to have a bell-shaped pH activity profile, which was retained in the essential aspartate mutants, but E174Q lost the basic pH limb of the curve, indicating that E174 is good candidate for the proton donating group necessary for catalysis. The general base needed for activity could not be unambiguously identified; although, of the essential aspartates, D172 is the only one conserved in other related glucosidases.

Amino Acid Sequence↗
PubMed1994

Glutathione can rescue the inhibitory effects of nickel on DNA ligation and repair synthesis.

The purpose of this investigation was to explore the reason why nickel chloride enhances the cytotoxicity and genotoxicity of ultraviolet (UV) light, but not that of methyl methanesulfonate (MMS) in Chinese hamster ovary cells. The cellular glutathione content was increased by treatment with MMS or nickel, but not with UV. Post-treatment with nickel synergistically raised the cellular glutathione content in MMS-treated cells; this phenomenon was not observed in UV-irradiated cells. Preventing cellular glutathione induction by buthionine sulfoximine increased the cytotoxicity, the frequency of sister chromatid exchange and prolonged the cell cycle in cells treated with nickel or MMS plus nickel. Pretreatment with N-acetylcysteine, a glutathione precursor, increased the clonogenic survival of cells treated with UV plus nickel. In vitro assays indicated that nickel could inhibit oligonucleotide ligation and the repair synthesis of UV- or MMS-treated plasmids and glutathione could relieve nickel inhibition. These results suggest that the enhancement by nickel of UV cytotoxicity and genotoxicity may be due to its inhibition of DNA repair, whereas treating cells with MMS plus nickel increased cellular glutathione levels, which may help in neutralizing the toxicity of nickel. The results also suggest that the activity of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione biosynthesis, may be increased by treatment with MMS, nickel and more so with MMS plus nickel.

Acetylcysteine↗
PubMed1993

A novel ryanodine sensitive calcium release mechanism in cultured human myometrial smooth-muscle cells.

In cultured human myometrial cells application of caffeine (1-30 mM) did not result in an elevation of intracellular Ca2+ ([Ca2+]i). Caffeine was found to reversibly inhibit both spontaneous and agonist-induced repetitive rises in [Ca2+]i possibly as a consequence of its ability to interfere with the binding of inositol trisphosphate (IP3) to the receptor on the sarcoplasmic reticulum. Brief applications of ryanodine (1-10 microM) were observed to elevate [Ca2+]i and repeated exposures to ryanodine could elicit Ca2+ transients of similar magnitude. Ryanodine was also observed to mobilise Ca2+ in cells bathed in nominally Ca(2+)-free solution. These observations suggest the presence of a novel type of ryanodine-sensitive Ca(2+)-induced Ca2+ release (R-CICR) system in human myometrial cells.

Adult↗
PubMed1993

Measurements of intracellular Ca2+ in cultured human myometrial smooth muscle cells bathed in low Na+ solutions.

In cultured human myometrial smooth muscle cells, removal of external Na+ activates repetitive increases in intracellular Ca2+ ([Ca2+]i). The Ca2+ transients persist in isotonic K+ solutions which suggests that the activity does not arise from regenerative changes in membrane potential. In nominally Ca(2+)-free solution, the activity disappears after a few cycles suggesting the involvement of internal stores. On Na+ removal, a background influx of Ca2+ may be responsible for activating the cyclical release of Ca2+ from internal stores. The absence of any effect of caffeine on resting [Ca2+]i suggests that the classical cardiac type of Ca(2+)-induced-Ca(2+)-release mechanism is not operating in these cells.

Adult↗
PubMed1993

Benign paroxysmal positioning vertigo with indeterminate cerebellar lesion: case report.

Of the numerous causes of dizziness, those that represent a life-threatening condition are rare. Physicians must guard against missing these rare but serious conditions while controlling the cost of the evaluation of patients who present with dizziness. This case study involving a 41-year-old female was written to illustrate the importance of systematic case history taking and of obtaining an ENG. The patient presented with classic symptoms of benign paroxysmal positioning vertigo (BPPV). The managing physician performed an MRI, which showed a cerebellar lesion. Results of a biopsy were negative. The patient's symptoms persisted, and she travelled to our clinic for further assessment. An ENG demonstrated a classic response to the Dix-Hallpike maneuvers, and a canalith repositioning maneuver was performed. The positioning dizziness resolved, and when contacted several months later, the patient stated she had remained asymptomatic.

Adult↗
PubMed1993

Human cartilage aggrecan CS1 region contains cryptic T-cell recognition sites.

Cartilage proteoglycan aggregates (PG) are candidate T-cell autoantigens in the pathogenesis of rheumatoid arthritis (RA). We have investigated the possibility that responses to class II-restricted T-cell recognition sites in human cartilage aggrecan (core protein) may depend upon whether these sites are available as free peptide antigens or as part of intact monomers. Analysis of mouse T-cell responses to intact or deglycosylated monomers, purified from human articular cartilage, and to synthetic peptides of the chondroitin sulphate (CS) attachment region homologous repeat sequence showed that recognition of T-cell epitopes in the CS1 region was strongly dependent upon the form of antigen used. The results show that the CS1 region contains cryptic T-cell recognition sites and raise the possibility that fragments of PG, released through the action of extracellular proteases in inflamed joints, may be capable of activating T cells with specificities for epitopes which are not made available following processing of intact PG. T cells with specificities for cryptic epitopes in PG may play a role in the pathogenesis of RA.

Aggrecans↗
PubMed1991

Comparative analysis of murine T lymphocyte responses to cartilage proteoglycans.

Cartilage proteoglycans are large molecules consisting of several sub-regions each of which comprises homologous repeating subunits. Comparisons of murine primed popliteal lymph node responses to human cartilage proteoglycans in BALB and B10 congenic mice showed that the major histocompatibility complex (MHC) influences T cell responsiveness to this antigen. H-2k and H-2d were higher responders than H-2b. Responses were MHC class II-restricted, and human cartilage proteoglycans were cross-reactive with mouse cartilage proteoglycans for a BALB/c T cell line. The proportion of proteoglycan-specific T lymphocytes in BALB/c primed popliteal lymph nodes was about 45% lower in females than males. These results show that in mice both MHC haplotype and sex can determine T lymphocyte responsiveness to cartilage proteoglycans. If the same mechanisms apply in humans they could be important in determining the HLA-DR haplotype associations and the predilection of rheumatoid arthritis for females.

Analysis of Variance↗
PubMed1990

A pilot study of paramedic-administered, prehospital thrombolysis for acute myocardial infarction.

We have implemented a pilot program of supervised paramedic administration of thrombolysis in the field. This program was begun on a small scale by training and equipping one paramedic service of one hospital. Four patients with acute myocardial infarction were rapidly and appropriately treated in the field. We compared these 4 patients with 21 patients who were brought to hospital by ambulance, but treated with thrombolysis conventionally in the emergency department. The patients in the field were treated an average of 86 minutes sooner than the patients treated in the emergency department.

Allied Health Personnel↗