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Biomedical subjects

C Lyons

Publications and source records attributed to C Lyons.

At least 37 records · Page 2Linked to original sources

Post keratoplasty dimensional and refractive change in contact lens and spectacle corrected cases.

Two groups of patients who had corneal transplantations for keratoconus were analysed retrospectively. One group had been visually corrected with corneal contact lenses and the second group had worn spectacles or used no optical correction. The reduction in post graft corneal astigmatism with time following removal of sutures was examined by the method of regression in groups. The results showed that the reduction in corneal astigmatism was significantly greater in the contact lens wearing group.

Astigmatism

HIV in women in the sex industry and/or injection drug users.

Women working in the sex industry are at risk for HIV infection acquired through intravenous drug use or sexual practices with steady sex partners, but there is no evidence that they are transmitting the virus to their customers. Most HIV infection in women in the United States is related to injection drug use (personal or that of a partner). Scapegoating and prejudice toward prostitutes and IVDUs is widespread. Services must be provided with attention to unique social and psychological concerns. Both educational and medical interventions must be sensitive and accessible, and, at times, must be provided outside traditional health care settings.

Female

Humoral immune responses in seals infected by phocine distemper virus.

Recently the isolation and characterisation of a morbillivirus which caused high mortality in common seals (Phoca vitulina) in 1988 have been reported. Because of the clinical and pathological similarity of the disease in seals to that of distemper in dogs, the name phocine distemper virus (PDV) has been proposed. There are marked differences in the virus-induced proteins of PDV compared to other morbilliviruses and the humoral immune response of moribund and dead seals to PDV was restricted to some of the internal antigens of PDV, similar to the response described earlier for canine distemper virus infection in dogs.

Animals

Isolation and characterization of iso-rANP, a new natriuretic peptide from rat atria.

Using a specific radioimmunoassay we have isolated and sequenced a new 45-amino acid peptide from rat atria which exhibits similar physiological and pharmacological properties to rat atrial natriuretic peptide (rANP). We have termed the new peptide iso-rANP, because of its functional and structural similarities to rANP. Amino acid sequence differences show that iso-rANP is genetically distinct from rANP. Iso-rANP has a single disulfide bond between residues 23-39 and this portion of the peptide shows substantial homology to rANP and to porcine brain natriuretic peptide (BNP). Little homology is evident at the N- and C-termini of iso-rANP and ANP. Iso-rANP is equipotent with rANP in eliciting diuresis, natriuresis and hypotension in the bioassay rat.

Amino Acid Sequence

Aldose reductase from human psoas muscle. Affinity labeling of an active site lysine by pyridoxal 5'-phosphate and pyridoxal 5'-diphospho-5'-adenosine.

The reaction of aldose reductase from human psoas muscle with either pyridoxal 5'-phosphate (PLP) or pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP) results in a pseudo first-order 2-fold activation of the enzyme with the stoichiometric incorporation of 1 mol of either reagent per mol of enzyme. However, in addition to an increase in Vmax there was also an increase in Km for both substrate, DL-glyceraldehyde, and coenzyme, NADPH. This resulted in an overall decrease in catalytic efficiency (kcat/Km). Spectral analysis indicated that activation by both PLP and PLP-AMP was accompanied by Schiff's base formation and epsilon-pyridoxyllysine was identified in hydrolysates of the reduced enzyme PLP-complex. Digestion of either PLP-modified or PLP-AMP-modified aldose reductase with endoproteinase Lys-C followed by high performance liquid chromatography purification and amino acid sequencing of the pyridoxyllated peptide revealed that PLP and PLP-AMP had modified the same lysine residue. A 32-residue peptide containing the essential lysine was found to be highly homologous with a segment of the sequence of both human liver aldehyde reductase and rat lens aldose reductase. A tetrapeptide (Ile-Pro-Lys-Ser) containing the essential lysine was identical in all three enzymes. These results highlight the close structural similarity between members of the aldehyde reductase family.

Adenosine Diphosphate

Identification of two phosphorylated threonines in the tail region of Dictyostelium myosin II.

We have previously purified and characterized a Dictyostelium myosin II heavy chain kinase which phosphorylates threonine residues (Côté, G. P., and Bukiejko, U. (1987) J. Biol. Chem. 262, 1065-1072). The phosphorylated threonines are located within a 34-kDa fragment which can be selectively cleaved from the carboxyl terminal end of the Dictyostelium myosin II tail. Tryptic and chymotryptic digests of the 34-kDa fragment phosphorylated with the kinase have now been performed and the resulting phosphopeptides isolated and sequenced. Two phosphorylated threonine residues have been identified, corresponding to residues 1833 and 2029 in the complete amino acid sequence of the Dictyostelium myosin II heavy chain. These amino acids are 87 and 283 residues, respectively, distant from the carboxyl terminus of the Dictyostelium myosin II heavy chain and are present in sections of the tail which seem to be alpha-helical coiled coils. In contrast, the three Acanthamoeba myosin II heavy chain phosphorylation sites are located within 10 residues of each other in a small globular domain at the carboxyl terminal tip of the tail (Côté, G. P., Robinson, E. A., Appella, E., and Korn, E. D. (1984) J. Biol. Chem. 259, 12781-12787). This suggests that the mechanism by which heavy chain phosphorylation inhibits the actin-activated ATPase activity and filament-forming properties of the two myosins may be quite different.

Calcium-Calmodulin-Dependent Protein Kinases

An unusual complication of coronary bypass surgery.

Four cases are discussed that had a preventable complication following coronary bypass surgery. Infection was associated with retained transthoracic pacemaker leads. These case reports should serve to remind us of the importance of removal of all possible foreign objects from our patients to prevent rare but serious complications.

Abscess

Alteration in the membrane fatty acid composition of human lymphocytes and cultured transformed cells induced by interferon.

The effects of interferon (IFN) treatment on the lipid composition of human peripheral blood lymphocytes or transformed cell line cells were investigated. The major phospholipid classes of lymphocytes as analyzed by 2-dimensional TLC and quantified by phosphorous content were phosphatidylcholine (PC, 43%) and phosphatidylethanolamine (PE, 28%), along with phosphatidylserine (9%) and phosphatidylinositol (8%). The membrane-impermeant reagent, trinitrobenzenesulfonate was used to covalently label cell surface PE. Fatty acid (FA) composition, determined by gas-liquid chromatography, showed a distinct pattern in each lipid class, with a predominance of 16 and 18 carbon fatty acids (FA) in PC and PE respectively. Arachidonic acid (20:4) and, to a lesser extent, docosahexanoic acid (22:6) were predominant in PE. The degree of unsaturation in each class, expressed as the ratio between unsaturated and saturated FA (U/S), was higher in PE (1.72) than in derivatized trinitrophenyl cell surface PE (TNP-PE, 0.57) or PC (0.64). Treatment with IFN resulted in an increased U/S ratio in cell surface PE (1.10) but not in other PE species (1.46). A small increase in unsaturation (0.88) was also observed in PC. Most of the increase in TNP-PE U/S was accounted for by an increase in 20:4 and a concomitant decrease in 18:0. These alterations were observed in the absence of quantitative change in the principal phospholipid classes or in the FA composition of the total lipid extract. In K562, a transformed cell line with characteristics of the erythromyeloid lineage, PE was found to be the most saturated lipid class with a predominance of 18:0. In PC, 16:0 was most abundant. Among unsaturated FA, 18:1 predominated in all lipid classes studied. Treatment with natural IFN alpha for 30 hr generally resulted in a decrease in saturated FA and an increase in unsaturated FA, which was most marked in PE. The U/S ratio in PE was highest in K562 cells during the time of maximal cell proliferation as assessed by tritiated thymidine incorporation. TNP-PE simultaneously decreased. Daudi cells, a B-lymphoblastoid cell line, demonstrated changes in FA composition of lipids with decreased saturated and monoenoic FA after IFN treatment, whereas DIF3 (a clone selected for lack of sensitivity to IFN) showed no change. These studies document changes in membrane FA composition of lymphocytes treated with IFN and correlate IFN-induced changes in transformed cell line FA with effects on proliferation. They further show the existence of a transverse molecular species asymmetry of PE in the plasma membrane of these cells which is altered after IFN treatment.

Cell Line

Mapping of activation changes within the acutely ischaemic canine specialised conduction system.

Ligation of the anterior septal artery was used to produce acute ischaemia of the specialised conduction system in ten dogs. Activation times at selected positions within the specialised conduction system were recorded. Marked delays of activation occurred between several discrete anatomic sites within the specialised conduction system. This study demonstrates that extremely slow conduction is common in localised areas of the acutely ischaemic infra-nodal conduction system. Heterogeneity of myocardial activation secondary to changes of speed of the conduction during acute septal ischaemia is postulated as a mechanism facilitating the occurrence of malignant ventricular arrhythmias.

Animals

The generation of small-plaque mutants during undiluted passage of canine distemper virus.

A culture of Vero cells persistently infected with undiluted-passage, large-plaque canine distemper virus was found to release small-plaque virus (SPV). This suggested that SPV could be generated by large-plaque virus (LPV). However, attempts to induce small-plaque mutants from LPV with 5-fluorouracil resulted in the production of virus that expressed a variable plaque type and induced a spectrum of disease in hamsters. In contrast, small-plaque mutants, shown to arise during undiluted passage of LPV, retained their small-plaque characteristic and resembled our original SPV isolate in their cytopathogenicity, immunogenicity, and neurovirulence for hamsters.

Animals

Transtelephonic monitoring of a tachycardia-terminating pacemaker.

A 66-year-old female with recurrent supraventricular tachycardia which worsened progressively was treated with an implanted tachycardia-terminating pacemaker after treatment with antiarrhythmic drug therapy had failed. The pacemaker had the capacity to detect and respond to tachyarrhythmias. Reliable sensing and termination of the patients tachycardia was accomplished in over 100 inductions of the tachyarrhythmia. Use of this tachycardia-terminating pacer has given us several new insights that may be important in the care and follow-up of all pacemaker patients.

Aged

Dual atrioventricular nodal pathways associated with a gap phenomenon in atrioventricular nodal conduction.

A 67 year old man underwent electrophysiologic study for evaluation of syncope. During atrial pacing at a basic cycle length of 600 ms, atrial premature stimuli were introduced at progressively shorter coupling intervals. The graph of atrial coupling intervals versus corresponding His bundle responses revealed an abrupt increase in atrioventricular (AV) nodal conduction time with coupling intervals from 320 to 340 ms. In an atrial coupling interval of less than 320 ms, conduction was again rapid until the effective refractory period of the atrium was reached. These unique findings are compatible with dual pathways and a gap phenomenon within the AV node.

Aged

Metabolism of androstenedione by guinea-pig peritoneal macrophages: synthesis of testosterone and 5 alpha-reduced metabolites.

Androstenedione metabolizing enzymes present in guinea-pig peritoneal macrophages were investigated using tritium-labeled androstenedione as the substrate. We found that the metabolites of [3H]-androstenedione produced by these macrophages were testosterone, 5 alpha-androstane-3,17-dione, isoandrosterone, androsterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol. The rates of metabolite formation remained linear as a function of time of incubation for approximately 30 min and with macrophage number up to 2 x 10(7) cells per ml. The formation of these metabolites in indicative that the following androstenedione metabolizing enzymes are present in guinea-pig peritoneal macrophages: 5 alpha-reductase, 3 alpha-hydroxysteroid oxidoreductase, 3 beta-hydroxysteroid oxidoreductase and 17 beta-hydroxysteroid oxidoreductase. It is possible, therefore, that the macrophage, in vivo, may play a role in the metabolism of blood-borne androstenedione to potent androgens. These hormones are important in the regulation of many biological processes, possibly including the activity of the macrophage itself.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

A possible role of the specialized conduction system in the conversion of ventricular tachycardia to ventricular fibrillation.

Electrode recordings from the right bundle branch, His bundle, and right atrium in a canine preparation enabled us to observe the activation of the ventricular myocardium and the specialized conduction system during the conversion of ventricular tachycardia to ventricular fibrillation. At times when ventricular tachycardia degenerated to ventricular fibrillation, asynchronous activation of the right bundle branch and the ventricular myocardium was frequently noted. Such asynchrony of activation was not seen during the spontaneous conversion of ventricular tachycardia to sinus rhythm. We suggest that this asynchronous activity produces increasing fractionation of ventricular activation fronts, which in turn yields fibrillation.

Animals

Sepsis and pacemaker malfunction.

An unconventional presentation of an elderly man with sepsis and a nonfunctioning permanent cardiac pacemaker is reviewed. Our interpretations of signs of an acute abdomen and laboratory evidence suggestive of acute cholecystitis did not lead to the correct diagnosis. The pacemaker electrode had perforated the myocardium and this event is believed to be secondary to bacterial endocarditis at the electrode tip. The therapeutic implications of this unique case are discussed.

Aged

The isolation of large and small plaque canine distemper viruses which differ in their neurovirulence for hamsters.

Large and small plaque-forming viruses were isolated from the Onderstepoort strain of canine distemper virus (CDV). Small plaque virus, which was released more slowly from infected cells than large plaque virus, readily established persistent infections in Vero cells, whereas large plaque virus required undilute passage to do so. All persistently infected cultures eventually released small plaque virus. No difference was found in the size of polypeptides induced by either plaque-purified viruses or virus released from persistent cultures. Both dilute and undilute passage, large plaque virus produced an acute neurological illness in weanling hamsters. whereas small plaque virus failed to produce any clinical signs of disease for 3 months after inoculation. After this period 50% of the animals infected with small plaque virus showed a general deterioration in their condition and lesions were observed in the brain which resembled those found in cases of large plaque virus infection. Serum-neutralizing antibody titres to CDV rapidly increased after infection with small plaque virus, whereas animals infected with large plaque virus had low or undetectable levels. All hamsters infected with small plaque virus and a small number which survived large plaque virus infection had elevated titres of antibody over a test period of 15 months.

Animals