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Biomedical subjects

M J Osborn

Publications and source records attributed to M J Osborn.

At least 73 records · Page 4Linked to original sources
PubMed1982

Hemodynamic and symptomatic consequences of ventricular pacing.

After implantation of a ventricular demand pacemaker (VVI), occasional patients continue to have dizziness, syncope, or near syncope ("pacemaker syndrome"). To identify patients in whom VVI pacing may have deleterious effects, we compared cuff blood pressure responses to VVI pacing with blood pressure responses to atrioventricular sequential pacing (DVI) or sinus rhythm in 50 consecutive patients. Patients with intact ventriculoatrial conduction had a much greater decrease in systolic blood pressure with VVI pacing (24 +/- 11 mm Hg) than those with ventriculoatrial dissociation (-4 +/- 15 mm Hg) (P less than 0.005). Patients who were in heart failure had a lesser decrease in blood pressure with VVI pacing than did those without failure (P less than 0.05); 13 of the 14 heart failure patients lacked ventriculoatrial conduction. Ten patients had symptomatic dizziness after VVI pacing; the incidence of symptoms was higher in patients with ventriculoatrial conduction (9 of 23) than in those without ventriculoatrial conduction (1 of 27) (P less than 0.003). We conclude that the presence of intact ventriculoatrial conduction appears to be a crucial determinant of the hemodynamic response to VVI pacing, and its presence may identify patients who are at risk for "pacemaker syndrome."

Adult↗
PubMed1982

The Wolff-Parkinson-White syndrome: a surgical approach.

Twenty-five patients with the preexcitation syndrome underwent operation for ablation of an accessory pathway. The patients were young (mean age 28.1 years) and 20% had congenital heart disease. In 24, markedly symptomatic refractory supraventricular tachycardia had been present for a mean of 12.6 years. The accessory pathway was right or left ventricular free wall in 22 patients and septal in 3 patients. Operation resulted in persistent ablation of the pathway in 80% of the patients. There was no perioperative mortality and no persistent complete heart block. During a mean follow-up of 15.6 months, 83.3% of patients with a preoperative history of supraventricular tachycardia had no recurrence of the arrhythmia. Two patients (8.3%) had macro-reentry paroxysmal supraventricular tachycardia related to a persistently functioning bypass tract. The remaining two patients had supraventricular tachycardia unrelated to a functioning accessory pathway. We conclude that the surgical treatment of patients with preexcitation syndrome (Wolff-Parkinson-White) is safe and effective. It should be considered (1) in patients who are markedly symptomatic with refractory supraventricular tachycardia, (2) in those who have the potential for sudden cardiac death, (3) in younger patients with symptomatic tachycardia in whom there is concern about the long-term effects of antidysrhythmic treatment, and (4) in patients with tachycardia who are undergoing cardiac surgery for repair of associated conditions.

Adolescent↗
PubMed1981

Patient-activated transvenous cardiac stimulation for the treatment of supraventricular and ventricular tachycardia.

Recurrent, drug-refractory sustained tachycardias present a difficult management problem. After invasive electrophysiologic study and extensive antiarrhythmic drug testing, a permanent transvenous lead system and radiofrequency stimulator that required patient activation for burst pacing were implanted in eight patients with refractory ventricular tachycardia. In a follow-up period of 2 to 28.5 months (mean 12) each patient has successfully terminated multiple episodes of recurrent tachycardia without complication. This therapeutic approach has allowed a reduction in antiarrhythmic drug dosage and adverse effects, has obviated the need for frequent hospital admissions resulting from recurrent tachycardia, and has met with excellent patient acceptance.

Adult↗
PubMed1981

Invasive electrophysiological study in the Jervell and Lange-Nielsen syndrome.

Repeated invasive electrophysiological studies in a 7-year-old boy with the classic Jervell and Lange-Nielsen syndrome disclosed increased ventricular refractoriness, unusual late diastolic endocardial waveforms, and the inability to induce ventricular fibrillation. Despite apparently beneficial electrophysiological responses to left stellate block, surgical left cervical sympathectomy was followed by spontaneous ventricular fibrillation, an unchanged QT interval and ventricular refractoriness, and persistence of late diastolic endocardial waveforms. These electrophysiological observations, which are unique, may reflect temporal and spatial inhomogeneity of repolarisation resulting from cardiac autonomic imbalance. The absence of electrophysiological change despite left stellate block is disconcerting and re-emphasises our incomplete understanding of the pathogenesis of syndromes involving long QT intervals. Invasive electrophysiological study should be considered in the assessment of future patients with this disorder.

Arrhythmias, Cardiac↗
PubMed1980

Lateral diffusion of lipopolysaccharide in the outer membrane of Salmonella typhimurium.

Gram-negative enteric bacteria are enveloped by two membrane systems. The inner or cytoplasmic membrane is responsible for the major metabolic functions including biosynthetic activities, while the major known functions of the outer membrane are primarily physical: it contains receptors for bacteriophages and bacteriocins; it contributes to the maintenance of cell shape; and it controls access of nutrient solutes and agents such as antibiotics and detergents to the cytoplasmic membrane. Several investigations have indicated that mobility of membrane components, particularly lipopolysaccharide, is essential for biogenesis of the outer membrane, and is a primary event in phage infection. To define more accurately the fluid dynamic properties of the outer membrane as related to function, we have now developed the capability to measure lateral diffusion coefficients in vivo of rhodaminated G30 lipopolysaccharide fused into Salmonella typhimurium G30A filamentous bacteria. The method used extends the FRAP procedure (fluorescence redistribution after photobleaching) to bacteria and the results demonstrate rapid diffusion of lipopolysaccharide (D = 2.0 +/- 0.9 x 10(-10) cm2s-1) over micrometre distances.

Cell Membrane↗
PubMed1980

Mechanism of assembly of the outer membrane of Salmonella typhimurium. Translocation and integration of an incomplete mutant lipid A into the outer membrane.

An incomplete precursor of lipid A produced by a mutant of Salmonella typhimurium conditionally defective in synthesis of 3-deoxy-D-mannooctulosonate (KDO) (Rick, P.D., and Osborn, M.J. (1977) J. Biol. Chem. 252, 4895-4903) is poorly translocated to the outer membranes. Approximately 40% of the lipid A precursor synthesized under nonpermissive conditions was recovered in the isolated inner (cytoplasmic) membrane fraction, and the rate of translocation to outer membrane in pulse-chase experiments was only 20% that of lipopolysaccharide. However, integration of the incomplete molecule into the outer membrane appeared to be similar to that of lipopolysaccharide in stability and irreversibility. The ultimate extent of translocation pulse-labeled precursor was comparable to that of lipopolysaccharide and the process was functionally unidirectional. Little or no reverse translocation from outer to inner membrane was detected during conversion of preformed lipid A precursor to lipopolysaccharide following return to permissive conditions.

Cell Membrane↗
PubMed1980

Biosynthesis of lipid A. In vivo formation of an intermediate containing 3-deoxy-D-mannoctulosonate in a mutant of Salmonella typhimurium.

The incomplete lipid A precursor produced by a mutant conditionally defective in synthesis of 3-deoxy-D-mannoctulosonate (KDO) is rapidly converted to lipopolysaccharide when the mutant culture is shifted from nonpermissive to permissive conditions (Osborn, M.J., Rick, P.D., and Rasmussen, N.S. (1980) J. Biol. Chem. 255, 4246-4251). An intermediate product which accumulates transiently during this conversion has been isolated and identified as a derivative of the lipid A precursor containing 2 residues of KDO. The intermediate lacks the saturated O-fatty acyl chains of the completed lipid A and is indistinguishable in composition and chromatographic properties from the previously described product obtained by enzymatic addition of KDO to isolated lipid A precursor (Munson, R.S., Jr., Rasmussen, N.S., and Osborn, M.J. (1978) J. Biol. Chem. 253, 1503-1511). The intermediate produced in vivo is rapidly converted to lipopolysaccharide under conditions in which its continued formation is interrupted by return of the culture to nonpermissive temperature. The results provide direct evidence that transfer of KDO to lipid A precedes addition of the saturated fatty acid residues.

Acetates↗
PubMed1980

Biosynthesis of lipid A. Formation of acyl-deficient lipopolysaccharides in Salmonella typhimurium and Escherichia coli.

The effect of cerulenin on conversion of an acyl-deficient precursor of lipid A to lipopolysaccharide was investigated in a mutant of Salmonella typhimurium (PRX22H9) conditionally defective in synthesis of 3-deoxy-D-mannooctulosonate (KDO). The precursor lacks both KDO and the saturated O-fatty acyl chains of lipopolysaccharide and contains beta-hydroxymyristate as sole fatty acid. Concentrations of cerulenin which inhibited de novo synthesis of fatty acids and lipopolysaccharide more than 95% had no effect on the rate or extent of conversion of preformed lipid A precursor to a lipopolysaccharide product. The product was identified as a polymer containing the Rc type core polysaccharide of PRX22H9 linked to the acyl-deficient lipid A unit of the precursor. The acyl-deficient lipopolysaccharide was translocated to the outer membrane at a normal rate. Lipopolysaccharide deficient in saturated fatty acids was also produced by a fabD mutant of Escherichia coli under conditions of limited endogenous fatty acid synthesis. The results indicate that prior incorporation of the saturated O-acyl chains of lipid A is not necessary for extension of the core polysaccharide chain and that synthesis of underacylated lipopolysaccharides occurs under conditions of restricted fatty acid synthesis which permit formation of the beta-hydroxymyristate-containing lipid A precursor.

Escherichia coli↗
PubMed1980

Lateral mobility in reconstituted membranes--comparisons with diffusion in polymers.

The diffusion coefficients (D) of lipopolysaccharide, phospholipid, and Escherichia coli matrix protein were determined in reconstituted multibilayer membranes. Over a range of protein concentration of 0--60% by weight, D for lipopolysaccharide decreased 10-fold, whereas D for phospholipid remained essentially constant. The diffusion coefficient of matrix protein at a concentration of 50% was less than or equal to 10(-12) cm2 s-1. These results are discussed in terms of a model for diffusion in polymeric networks.

Bacterial Proteins↗
PubMed1978

Biosynthesis of lipid A. Enzymatic incorporation of 3-deoxy-D-mannooctulosonate into a precursor of lipid A in Salmonella typhimurium.

The cell envelope fraction of Salmonella typhimurium contains an enzyme system which catalyzes transfer of 3-deoxyoctulosonate (KDO) from CMP-KDO to an incomplete, KDO-deficient precursor of lipid A. The enzyme system is firmly membrane-bound, but has been solubilized by treatment with nonionic detergent at alkaline pH and partially purified. Both the particulate and partially purified fractions catalyzed formation of a single reaction product containing 2 residues of KDO. Periodate oxidation of the purified product permitted tentative identification of the KDO disaccharide structure as KDO2-4KDO.

Cell Membrane↗
PubMed1978

Bacteriophage P22 is not a likely probe for zones of adhesion between the inner and outer membranes of Salmonella typhimurium.

Thin-section electron micrographs of plasmolyzed Salmonella typhimurium infected with bacteriophage P22 demonstrated that phage adsorbed to cells over sites of inner- and outer-membrane contact. Efforts were made to isolate such adsorption sites by infection of cells with 35S- and 32P-labeled phage and by separation of the membranes on sucrose gradients. At 37 degrees C, about 75% of the 35S radioactivity could be recovered in a region of intermediate density between the inner and outer membranes. This region (phi band) did not contain 32P. The gradient profile was independent of the multiplicity of infection (between 0.2 and 50) and of the presence or absence of chloramphenicol, dinitrophenol, or cyanide. However, ethylenediaminetetraacetate, when present during the infection step, prevented the formation of phi band. The density of phi band was at least 1.30 g/cm3, as demonstrated by prolonged centrifugation on a D2O-sucrose gradient. phi Band was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electron microscopy to contain empty phage heads and contaminating cellular debris. In purified preparations, phage heads were the only structures, visible by negative staining, and very little cellular phospholipid or protein was associated with the phage proteins (less than 2% and 30% by weight, respectively, as determined by using [3H]glycerol or [3H]leucine). The residual cellular protein included all of the major outer-membrane proteins rather than any one specific protein. These results are interpreted as indicating that phi band probably does not contain adhesion site material stably associated with phage heads.

Adsorption↗
PubMed1977

Interaction of Salmonella typhimurium with phospholipid vesicles. Incorporation of exogenous lipids into intact cells.

Incubation of intact cells of Salmonella typhimurium with bilayer phospholipid vesicles results in significant transfer of vesicle lipids to the cells. The transfer requires Ca2+ or spermine, and is dependent on time, temperature, the concentration and composition of the vesicles, and the nature of the cellular lipopolysaccharide. The process results in bulk transfer of vesicle lipids to the cells rather than reciprocal molecular exchange between vesicles and the outer membrane. All components of mixed lipid vesicles, including cholesteryl oleate and lipopolysaccharide, are transferred to the cells in a ratio similar to that of the donor vesicles. The properties of the transfer process are consistent with direct fusion of vesicles with the outer membrane of the cell.

Calcium↗