Search PubMed⌕ Search

Biomedical subjects

J R Miller

Publications and source records attributed to J R Miller.

At least 163 records · Page 9Linked to original sources

The safety of egg-containing vaccines for egg-allergic patients.

Forty-two patients with a history of egg sensitivity were evaluated for receiving avian-grown vaccines. After giving a history and undergoing physical examination, each patient was skin-tested with egg antigens and six egg-propagated vaccines, given an oral egg challenge, and finally, when possible, given a vaccine challenge. Thirty-seven of the 42 patients (88%) were ultimately given one or more of the vaccines with no reactions or only minimal ones to both egg protein and vaccine; they had mild reactions consisting of pruritus, headache, and apprehension. Immunization was withheld from three patients who had a history of severe reactions after egg ingestion and strongly positive skin reactivity to both egg and vaccine. A history of egg intolerance should not, by itself, disqualify a patient from receiving one of these vaccines. However, a history of exquisite sensitivity to egg protein indicates that a severe vaccine reaction is likely. An intradermal skin test utilizing 0.02 ml of a 1:100 dilution of the vaccine and resulting in a wheal of greater than 5 mm was found to be the test that most reliably predicted those patients who should not receive the vaccine.

Administration, Oral↗

Effect of hemorrhage and anoxia on hepatic gluconeogenesis and potassium balance in the rat.

Previous investigations have demonstrated impairment of hepatic gluconeogenic activity during both hypovolemia and sepsis, but the mechanisms responsible remain unclear. The present study was designed to determine the influence of lack of oxygen on gluconeogenesis independent of humoral factors, products of ischemic peripheral tissues or pH changes. Livers obtained from Sprague-Dawley rats fasted 24 hours were perfused with Krebs-Henseleit buffer containing 5 mM lactate for 30 minutes. In the control group (n = 8) perfusion was continued; in others, anoxia was induced by perfusing with buffer equilibrated with 95% N2 and 5% CO2 for periods of 15, 30, or 60 minutes (n = 4, 5, and 5, respectively). The initial conditions were then reinstituted for an additional 45 minutes. Anoxia caused hepatic release of K+, indicative of disordered hepatic cellular ionic gradients and an abrupt cessation of gluconeogenesis. Reoxygenation partially reversed these alterations but some impairment of gluconeogenesis persisted and the degree of uptake of K+ from the perfusion media was decreased as the duration of anoxia increased. The degree of restoration of gluconeogenesis after a period of anoxia was closely associated with restoration of cellular uptake of K+. By comparison, livers taken from hypovolemic animals maintained at a mean arterial blood pressure of 40 mm Hg until the beginning of the decompensatory stage of shock exhibited a gluconeogenic capacity of only 41% of control animals and was comparable to the compromise induced by between 30 and 60 minutes of anoxia. These results suggest that the abilities to restore hepatic electrolyte balance and gluconeogenesis after oxygen deprivation are affected in parallel and may reflect a common dependence on the restoration of ATP stores after the insult.

Animals↗

The lidgap defect in mice: update and hypotheses.

The open eye defect in the mouse can result from the action of mutant genes or of teratogens. Among the genetic forms, the lidgap series poses a particular challenge. The lidgap defect appears to be a complex genetic trait and may serve as a model for the genetic analysis of other genetically complex morphological defects in mammals. Extensive breeding data, together with data on the response of the trait to in utero treatment with cortisone, have been analyzed. The results lead us to propose a model involving a single major locus with a series of alleles of graded strength, hypomorphs. The ranking is lg greater than lgstn = lgSt greater than lgM1. The lg/lg genotype alone can be sufficient to produce the lidgap trait, but the "weaker" alleles require a second or even third locus acting in the same pathway. In addition, there is evidence that a recessive suppressor locus is present in the system. These hypotheses are testable and some experiments to develop them further are discussed.

Alleles↗

The role of myosin light chain kinase phosphorylation in beta-adrenergic relaxation of tracheal smooth muscle.

Myosin light chain kinase from smooth muscle has been shown to be phosphorylated by cyclic AMP-dependent protein kinase, which leads to a decrease in the affinity of the kinase for Ca2+ . calmodulin and, hence, a decrease in enzymatic activity. This event has been proposed as a mechanism for the relaxation of smooth muscle in response to increased intracellular concentrations of cyclic AMP. The ratio of myosin light chain kinase activities measured in the presence of 4 microM or 100 microM Ca2+, at 1 microM calmodulin, permits evaluation of such a change in the calmodulin activation properties of myosin light chain kinase. This activity ratio was decreased by phosphorylation of either purified bovine tracheal smooth muscle myosin light chain kinase, or the endogenous myosin light chain kinase in a homogenate of tracheal smooth muscle, with the addition of the catalytic subunit of cyclic AMP-dependent protein kinase. The ratio was unchanged, however, by activation of the endogenous cyclic AMP-dependent protein kinase in homogenates of tracheal smooth muscle by the addition of cyclic AMP. Incubation of tracheal smooth muscle with isoproterenol, at a concentration sufficient to relax the muscle and to increase phosphorylase a formation, had no effect upon the activity ratio. Incubation of tracheal smooth muscle for 2 hr in the presence of carbachol resulted in a transient increase and then a decrease in myosin light chain phosphate content to control values with no decrease in isometric force. The addition of isoproterenol at 2 hr still resulted in relaxation. These findings are inconsistent with a role of myosin light chain kinase phosphorylation in mediating relaxation of tracheal smooth muscle by beta-adrenergic agonists. Cyclic AMP-dependent effects on cytoplasmic calcium concentrations may be more important in mediating relaxation.

Adrenergic beta-Agonists↗

Phosphorylation of myosin light chain in skeletal and smooth muscles.

Significant differences in the properties of myosin light chain phosphorylation in skeletal and smooth muscles may be important in considering the role of myosin phosphorylation in contraction. Repetitive, low-frequency stimulation of fast-twitch skeletal muscle resulted in phosphorylation of myosin light chain. Some of the factors leading to phosphorylation under these conditions include 1) partial activation of myosin light chain kinase with each stimulus, 2) a slow rate (t1/2 = 1 s) of inactivation of the kinase activity, and 3) a very slow rate of dephosphorylation by myosin light chain phosphatase. Myosin light chain phosphorylation was correlated with potentiation of isometric twitch tension in posttetanic potentiation and staircase responses. Stimulation of contraction in bovine tracheal smooth muscle by the cholinergic agonist carbachol was correlated with phosphorylation of the myosin light chain. The initial rate and maximum extent of phosphorylation during the first minute of stimulation was dependent on the concentration of carbachol. Phosphate incorporation into light chain declined after 1 min whereas isometric tension was maintained. beta-Adrenergic inhibition of tension development was accompanied by a decrease in the rate and extent of phosphorylatable myosin light chain phosphorylation but was not associated with reduced affinity of myosin light chain kinase for calcium-calmodulin.

Animals↗

Combined effects of sodium nitroprusside and propranolol on hypoxic pulmonary vasoconstriction.

Recent clinical experience and previous experimental work indicate that propranolol may reverse sodium-nitroprusside-induced inhibition of hypoxic pulmonary vasoconstriction (HPV). Accordingly, the authors decided to test this possibility in an experimental model that allows direct examination of pharmacologic influence on HPV. Six mongrel dogs were anesthetized with pentobarbital and intubated. Following a left thoracotomy, the left lower lobe (LLL) was ventilated independently but synchronously with the rest of the lung. Selective hypoxia of the LLL (95% nitrogen and 5% CO2) caused a 59 +/- 6% (mean +/- SE) decrease in the electromagnetically measured fraction of the cardiac output perfusing the LLL and a 287 +/- 65% increase in the pulmonary vascular resistance of the LLL from their respective prehypoxic values. Propranolol, 1 mg/kg intravenously, caused a 76 +/- 5% beta-blockade, as determined by an isoproterenol infusion test, but did not cause a significant change in the LLL HPV response. Sodium nitroprusside (SNP) infusion, caused a 38 +/- 4% decrease in systemic arterial pressure, and nearly abolished LLL HPV. Most important, the addition of propranolol to sodium nitroprusside did not significantly change the SNP induced inhibition of LLL HPV. The authors conclude that in acute lung disease, propranolol does not alter lobar HPV and does not reverse sodium nitroprusside inhibition of lobar HPV.

Animals↗

Closing the gap in quality assurance: A tool for evaluating group leaders.

A commitment to quality assurance means offering a cycle of feedback to those being evaluated. How to meet that commitment was the question asked by the Health Education Department of a large Health Maintenance Organization whose more than 70 facilitators annually provide instruction for over 3,000 enrollees. As part of the multi-faceted endeavor to develop a systematic quality assurance program for the department's offerings, a reliable participant-scored standardized tool had to be constructed. The staff of the department first identified two concepts as critical for quality instruction: interpersonal skills and technical competence. Based on these criteria a 49-item questionnaire was developed and tested during "pre-pilot" and pilot stages. By computer analysis, 27 items with an alpha-reliability coefficient of .94 remained to form the tool the department uses. The development of the evaluation tool and its use are described.

Consumer Behavior↗

Mass spectral rearrangements of acyclic dialkylnitrosamines: n-nitrosomethyl-n-butylamine and analogs.

Electron-impact mass spectra of N-nitrosomethyl-n-butylamine, 5 of its specifically deuterated anologs and its methyl-n-hexyl and methyl-n-octyl homologs have been examined. Hydrogen abstraction by the nitrosamino moiety dominates the rearrangement ions, especially at low ionization energy. All compounds exhibited the (M-OH)+ ion, for which the hydrogen abstraction is non-specific, involving the C-2 and C-3 positions in the methylbutyl homolog. In the same compound, the M-propene ion required the specific transfer of hydrogen from C-3. A double hydrogen migration was demonstrated for the formation of the m/z 61 ion, CH5N2O+, corresponding to a protonated diazotic acid. A skeletal rearrangement is indicated by the ion C4H9O+. The new information should prove helpful in structure studies of this class of compounds.

Mass Spectrometry↗

Prolonged intracerebral infection with poliovirus in asymptomatic mice.

A heretofore unrecognized prolonged asymptomatic infection has been identified in mice intracerebrally inoculated with Lansing strain type II poliovirus. Virus was detected by infectivity assay and nucleic acid hybridization and was found in brains as long as 77 days after injection. Viral RNA replication occurred, indicating that persisting virus was not an inactive residuum of the infecting dose. Virus was sometimes found by infectivity even when viral RNA could not be demonstrated by hybridization, but detection by nucleic acid hybridization alone never occurred. Among 56 animals--including mice that died of infection, mice with prolonged infection, and survivors from which virus was not recovered--no animal had a serum neutralization titer above 1:2 in a plaque reduction assay Moreover, brain homogenates of 30 survivors without virus did not have neutralization titers above 1:4 in the plaque reduction assay. These findings were the same as in mock-infected mice.

Animals↗

A transcriptionally active pseudogene in xenopus laevis oocyte 5S DNA.

DNA that encodes the Xenopus laevis 5S pseudogene is transcribed following microinjection into oocyte nuclei. Transcription in injected oocytes is accurate, is mediated by RNA polymerase III and is initiated at the first nucleotide of the pseudogene. The level of pseudogene transcription can be as high as 85% of that of the normal 5S gene. The results suggest that the observed absence of pseudogene transcripts of defined length in vivo probably is due to inefficient termination of transcription.

Animals↗

Respiratory and cardiovascular responses to PEEP in artificially ventilated patients after cardiopulmonary bypass surgery.

The respiratory and haemodynamic effects of incremental levels of positive and expiratory pressure (PEEP) to 9 cm H2O were studied in ten adult patients 3--6 hours after uneventful cardiopulmonary bypass surgery. Functional residual capacity was increased and deadspace-tidal volume ratio tended to fall, the latter approaching significance at +6 and +9 cm PEEP. Thus lung volume was increased and there was a tendency to improved gas distribution to the alveoli. However there was no significant change in PaO2, alveolar-arterial oxygen tension difference or venous admixture. Cardiac index, and left ventricular strokework index were marginally depressed at 6 cm PEEP and further at 9 cm, while right atrial pressure and pulmonary artery occlusion pressure were raised at 9 cm PEEP. It would appear that low levels (3--6 cm) of PEEP do not improve gas exchange in the lungs to any worthwhile degree, and levels (6--9 cm) may impair cardiac performance.

Cardiopulmonary Bypass↗