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Biomedical subjects

A M Murphy

Publications and source records attributed to A M Murphy.

At least 55 records · Page 3Linked to original sources
PubMed1992

Active and passive electrical properties of isolated canine cardiac Purkinje fibers under conditions simulating ischaemia: effect of diltiazem.

The effect of a calcium channel blocker diltiazem on the electrical properties of canine Purkinje fibers superfused in a milieu similar to that occurring in acute myocardial ischaemia was studied. Action potential parameters, passive electrical properties, and conduction velocity were measured using conventional microelectrode techniques. Superfusion with glucose-free Tyrode's solution containing 9 mM K+, gassed with 100% N2 at pH = 6.5 ('ischemic solution') significantly reduced the maximal diastolic potential, action potential duration, maximal upstroke velocity, conduction velocity and length constant, while input resistance and longitudinal resistance were elevated and membrane resistance remained unchanged. Diltiazem (1 microM) alone reduced only the action potential duration, while all other parameters were unaffected. Pretreatment with diltiazem did not fully prevent the effects of ischemic superfusion; however, the ischaemia-induced decrease in length constant was not significant in the presence of diltiazem. In addition, the increase in longitudinal resistance during ischaemia was significantly reduced following diltiazem pretreatment. This decrease in longitudinal resistance may contribute to the improvement of ischaemia-induced conduction delay observed in intact animals and may be related to a reduction of ischaemia-induced increase in intracellular free Ca2+.

Action Potentials↗
PubMed1991

Influenza A(H1N1): a widening spectrum?

OBJECTIVE: To study the incidence of H1N1 influenza from 1977 to 1988 in unvaccinated volunteers and the effects of continuing minor antigenic change (antigenic drift) in the virus. DESIGN: Prospective study by a group of general practitioners, backed up by virological findings. PARTICIPANTS: Mainly patients of the general practitioner group, also some doctors and members of staff. There were 287 participants during 1977-1981, and 207 at the end of 1988. INTERVENTION: Any participant deemed to be "at risk" was encouraged to be vaccinated and to withdraw from the study. BACKGROUND: In 1957, H1N1 subtype influenza had been displaced by H2N2 (Asian) subtype. In 1968, H2N2 was displaced by H3N2 (Hong Kong) subtype. During 1977, H1N1 influenza unexpectedly reappeared in Asia, and spread widely. The resurgent strain, designated A/USSR/90/77(H1N1), caused world pandemics, attacking (almost exclusively) persons who had been born since the 1950-1951 northern winter and causing negligible mortality. It did not displace the current H3N2 strain, and strains of both subtypes have continued to emerge independently. HYPOTHESIS: Antigens of A/USSR resembled closely those of the 1950-1951 H1N1 strain, which apparently was rendered antigenically inert between 1951 and 1976 (possibly frozen) and was reactivated during 1977. Antigenic drift was then resumed. MAIN OUTCOME MEASURE: The A/USSR/90/77 strain and its close successor, A/Brazil/11/78, attacked mainly the young, whose previous exposure to H1N1 antigens had been minimal or zero. Mortality during the A/USSR pandemics was negligible because death from influenza in people aged less than 30 years is rare. Would continuing antigenic drift ultimately widen the H1N1 spectrum of attack? RESULT: During the epidemic of 1988, A/Taiwan/1/86(H1N1) attacked a wider range of age groups than had A/USSR or A/Brazil. CONCLUSION: Assuming that H1N1 viruses continue to undergo further antigenic drift, an ever widening age spectrum of H1N1 attack may be expected.

Antibodies, Viral↗
PubMed1991

Molecular cloning of rat cardiac troponin I and analysis of troponin I isoform expression in developing rat heart.

We have isolated and sequenced a cDNA encoding rat cardiac troponin I. The predicted amino acid sequence was highly identical with previously reported chemically derived amino acid sequences for rabbit and bovine cardiac troponin I. Clones for slow skeletal muscle troponin I were also obtained from neonatal rat cardiac ventricle by the polymerase chain reaction. The nucleotide sequences of these clones were determined to be more than 99% identical with a previously reported rat slow skeletal troponin I cDNA [Koppe et al. (1989) J. Biol. Chem. 264, 14327-14333]. The troponin I clones hybridized to RNA from the appropriate muscle from adult animals. However, RNA from fetal and neonatal rat heart also hybridized with the slow skeletal troponin I cDNA, demonstrating its expression in fetal and neonatal rat heart. Slow skeletal troponin I steady-state mRNA levels decreased with increasing age, but cardiac troponin I mRNA levels increased through fetal and early neonatal cardiac development. Thus, during fetal and neonatal development, slow skeletal and cardiac troponin I isoforms are coexpressed in the rat heart and regulated in opposite directions. The degree of primary sequence differences in these isoforms, especially at phosphorylation sites, may result in important functional differences in the neonatal myocardium.

Amino Acid Sequence↗
PubMed1991

Troponin I isoform expression in human heart.

Troponin I is the inhibitory component of troponin, the thin filament regulatory complex in striated muscle. Separate genes encode cardiac-specific fast and slow skeletal-specific isoforms of this protein. We have previously described gene switching from the slow skeletal to the cardiac troponin I mRNA expression in developing rat heart. The purpose of this work was to characterize the expression of the different troponin isoforms in the human heart. Human cardiac and slow skeletal troponin I cDNA probes were obtained by screening an adult cardiac cDNA library and by Taq polymerase amplification of RNA from an infant's heart, respectively. We found that the cardiac troponin I isoform is tissue-specific in its expression in normal adult tissues. RNA blot analysis of cardiac ventricular RNA from infants with congenital heart disease and from an adult with cardiomyopathy revealed expression of human cardiac troponin I in all analyzed specimens. In addition, we found expression of slow skeletal troponin I mRNA and protein in infant hearts but no detectable mRNA expression in the adult heart. We conclude that troponin I isoforms are developmentally regulated in the human heart by a mechanism similar to that in the rat heart.

Amino Acid Sequence↗
PubMed1990

Induction of B cell responsiveness to growth factors by Epstein-Barr virus conversion: comparison of endogenous factors and interleukin-1.

Immortalized B lymphocytes produce a factor(s) that stimulates growth of B cell lines carrying Epstein-Barr virus (EBV). Stimulatory supernatants derived from B cells also exhibit interleukin-1 (IL-1) activity in costimulator assays with the D10.G4.1 helper T cell line. Experiments with purified macrophage-derived IL-1 and recombinant IL-1 beta demonstrate that IL-1 stimulates proliferation of the cell lines that respond to the factors from B lymphocyte lines. One B cell line, Ramos, an EBV-Burkitt's lymphoma, contrasts with other B cell lines in that it is refractory to the growth enhancing effects of B cell conditioned medium and macrophage-derived IL-1. When EBV was introduced into Ramos cells, growth was enhanced by the factor(s) in B cell conditioned medium (six out of seven lines); growth of EBV-converted Ramos lines (six out of seven lines) also was enhanced by IL-1. These findings demonstrate that infection of a non-responsive transformed B lymphocyte by EBV induces cellular responsiveness to factor-mediated growth stimulation.

B-Lymphocytes↗
PubMed1990

Developmental difference in the stimulation of cardiac myofibrillar Mg2(+)-ATPase activity by calmidazolium.

We probed possible developmentally related changes in thin filament activity in rat hearts with the aid of calmidazolium (CDZ). CDZ is a calmodulin antagonist that also binds to troponin C and stimulates Ca2+ troponin C-dependent activation of cardiac myofibrillar contractile activity. In paired experiments, we compared the effects of 10, 30, 50, 70, and 100 microM CDZ on Mg2(+)-dependent ATPase activity of myofibrillar preparations from adult and neonatal rat hearts. Over the dose-response curve, the ATPase activity of neonatal myofibrils was significantly less stimulated than was the ATPase activity of the adult preparations. To know whether this difference in response to CDZ was related to differences in the thin or thick filaments, we studied hybrid adult and neonatal myofibrillar preparations. These hybrid myofibrils had native thin filaments, but the thick filaments were displaced with rabbit skeletal myosin. The relative insensitivity of the neonatal preparations to the effect of CDZ was retained in the hybrid myofibrils. This suggested that developmental transitions in the population of thin filament proteins are responsible for the difference between adult and neonatal myofibrils in their response to CDZ. Recently, we and others have reported developmental switching of troponin I isoforms in the rat heart. Since troponin I reacts strongly with troponin C in a Ca2(+)-dependent manner, we speculate that developmentally related changes in troponin I isoforms may contribute to the differential effect of CDZ in neonatal cardiac myofibrils.

Age Factors↗
PubMed1989

Blood pressure and cardiac output during exercise: a longitudinal study of children undergoing repair of coarctation.

Data were examined from 21 children who underwent graded exercise studies prior to and within 5 years after repair of coarctation. A control group of 10 normal children was also studied longitudinally on two occasions. The exercise was performed on an upright bicycle ergometer using a continuous graded exercise protocol. Parameters measured were heart rate, systolic and diastolic blood pressure at rest, and these pressures at the maximal voluntary exercise level. In addition, a subset of patients and controls had measurement of cardiac output by a modified acetylene rebreathing technique. Results indicate that coarctation patients had significant elevation of systolic and diastolic blood pressures at rest (p less than 0.001 for both) and with exercise (p less than 0.02 for both) prior to surgery. The group mean values for systolic and diastolic blood pressure did not differ from control values after surgery; however, some individuals continued to have hypertension at rest when compared to population-based norms. Heart rate, cardiac index, and stroke volume index did not differ from those of control subjects either at rest or during exercise before or after surgery. In conclusion, a group of coarctation patients studied longitudinally demonstrated marked improvement in both systolic and diastolic hypertension after surgery. The findings of normal cardiac output and stroke volume indices may have implications for the etiology of postoperative hypertension.

Aortic Coarctation↗
PubMed1987

Age-related digoxin effects in an intact canine model.

The inotropic and electrophysiologic effects of digoxin were studied in anesthetized neonatal and adult dogs to test the hypothesis that digoxin had comparable effects in these groups. Recordings of the ECG and central arterial pressure were made starting at 5.75 hours after an intravenous injection of 50 micrograms/kg of the drug. Parameters measured were heart rate (HR); PR interval; mean, systolic, and diastolic blood pressure; preejection period (PEP); and ejection time (ET). Two indices of systolic function were calculated, the systolic time interval (STI = PEP/ET) and total electromechanical systole (TMS = PEP + ET), which was indexed for HR. There was no significant difference from control animals in either the adult or neonatal groups in the PR interval or blood pressure. In the neonatal dogs, HR and STI were also not significantly different from control. However, in the neonatal dogs, there was a significant decrease in the indexed TMS, 288 +/- 7 vs 270 +/- 11 msec (p less than 0.01). In the adult animals, HR decreased from 116 +/- 35 to 66 +/- 25 bpm (p less than 0.01), STI decreased from 0.559 +/- 0.059 to 0.447 +/- 0.069 (p less than 0.01), and indexed TMS decreased from 333 +/- 10 to 291 +/- 13 msec (p less than 0.001). Two-way analysis of variance demonstrated that digoxin differed significantly in its effects on HR (p = 0.005), STI (p = 0.018), and TMS indexed for HR (p = 0.003) in neonatal compared to adult dogs. Pharmacokinetic studies showed a rapid distribution phase and equilibrium conditions at the time of physiologic measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Duplex ultrasound in the assessment of renal transplant complications.

Duplex ultrasound was performed on 21 patients with renal transplants to assess the feasibility of detection of complications and, in particular, acute rejection and vascular abnormalities. A comparison of the results of Doppler waveform analysis in the transplant renal artery and morphological features on real time scanning in the detection and follow up of acute rejection was made. It was noted that there were characteristic alterations of Doppler shift spectral pattern in acute rejection, and these characteristics were more accurate, appeared earlier and showed a more consistent response to anti-rejection treatment than morphological changes demonstrated by real time ultrasound. Three patients had vascular abnormalities correctly predicted by duplex ultrasound and confirmed by angiography. These findings suggest that duplex ultrasound should be the investigation of choice in the initial assessment and follow up of renal transplant.

Female↗
PubMed1987

Aerial respiration facilitates growth in suspension-feeding anuran larvae (Xenopus laevis).

Xenopus laevis tadpoles are midwater suspension-feeders that use buccopharyngeal surfaces for both food capture and aquatic respiration, but also have functioning lungs well before metamorphosis. To examine the effect of aerial respiration on premetamorphic growth and development in this species, tadpoles were raised in normoxic water for from one to three weeks at three different concentrations of food (yeast cells in suspension). At each food concentration the larvae were either allowed or denied access to air. Xenopus larvae reached greater snout-vent lengths, weighed more and developed more rapidly when allowed to breathe air. The difference in growth and development between those tadpoles with and without access to air was proportional to the concentration of particulate matter. In the extreme, tadpoles denied access to air at the highest food concentration all asphyxiated shortly after the start of the experiment. Xenopus tadpoles faced with the functional conflict of using buccopharyngeal surfaces for both feeding and respiration retard ingestion. They do this, however, not by ceasing mucus outflow to their branchial food traps, as has been speculated previously, but rather by capturing food particles in mucus and then expectorating it. Lungs appear to be advantageous to aquatic organisms even in normoxic water in that they allow buccopharyngeal surfaces to be dedicated fully to feeding rather than respiration.

Air↗