Search PubMed⌕ Search

Biomedical subjects

J A Lee

Publications and source records attributed to J A Lee.

At least 19 recordsLinked to original sources
PubMed1992

Hepatic reinnervation following orthotopic liver transplantation in man.

We have studied changes in the pattern of intrinsic hepatic innervation in sequential liver biopsies from 16 patients who underwent orthotopic liver transplantation. Seventy-one needle biopsies were used, including specimens obtained at the time of transplantation (time zero) and up to 4 years post-transplantation; five transplant hepatectomy tissue blocks removed 3-32 months after transplantation were also assessed. Paraffin sections were immunostained with anti-PGP 9.5 and anti-S-100 to identify nerve fibres. All 'time zero' biopsies contained portal nerves and all but two showed staining of parenchymal fibres. After 1 week, no subsequent biopsies contained parenchymal fibres. The disappearance of portal fibres was less rapid and showed greater variability between patients, but they had all disappeared by 6 weeks and there was no positive staining between 6 and 60 weeks. Thereafter, a minority of biopsies showed innervation of a few small portal tracts. Samples from the porta hepatis, hepatectomy specimens, and needle biopsies containing large tracts showed persistence of major nerve trunks at all stages. Abnormally large nerve bundles were seen in some of these areas. The pattern of nerve staining showed no obvious relationship to the intensity of rejection changes. Our results suggest that there is a limited, delayed capacity for regeneration of portal, but not parenchymal, fibres in the transplanted human liver. The physiological significance of this long-term parenchymal denervation in transplanted livers remains to be determined.

Humans↗
PubMed1992

Stimulation of c-fos and c-jun gene expression and down-regulation of proenkephalin gene expression in C6 glioma cells by endothelin-1.

The linkage between the transmembrane signal transduction system utilized by endothelin and alterations in gene expression has been investigated in C6 glioma cells. Treatment of C6 cells with endothelin-1 caused a rapid and transient 5-fold increase in c-fos and c-jun mRNA levels, followed by a decrease at 4 h. Dose-response studies indicated that 1 nM endothelin-1 caused half-maximal induction of c-fos mRNA 0.5 h after treatment and that maximal induction was elicited with a concentration of 10 nM. Actinomycin D totally abolished the rapid increase in c-fos mRNA caused by endothelin, indicating that the effect is at the transcriptional level. Endothelin-1 caused a decrease in proenkephalin mRNA to 50% of control levels at 4 h after treatment and had no effect on histone H4 mRNA over a 24 h period that was examined. These data indicate that receptor binding of endothelin-1 leads to rapid changes in the expression of immediate-early response genes which may cause more prolonged changes in the expression of AP-1 and/or CREB target genes in the nervous system.

Animals↗
PubMed1992

Etiology, risk factors, epidemiology, and public health issues in melanoma and other cutaneous neoplasms.

The cytogenetic features of melanoma, including the contribution of specific genes, are beginning to be unraveled. Reproductive factors have been shown to have little relationship to melanoma. The puzzles over apparent systemic effects of exposure have persisted, however. Evidence was published that the history of reaction to sun exposure altered when a diagnosis of melanoma was made. An interesting suggestion was made that the classic melanoma risk factors are associated with promotion rather than initiation of the disease. There is further evidence that exposure decreases melanoma risk in people who tan well but increases it in those who do not. Also reviewed is the evidence that the ozone layer of the stratosphere began to decrease in thickness under the influence of the chlorofluorocarbon gasses.

Heliotherapy↗
PubMed1992

Disappearance of hepatic parenchymal nerves in human liver cirrhosis.

The normal human liver receives a substantial autonomic innervation that is thought to subserve motor, metabolic, and sensory functions. In this study an antibody to a neural axoplasmic protein (PGP 9.5) was used to visualise autonomic nerves in tissue from normal, precirrhotic, and cirrhotic livers. Nerve fibres were readily identified in the parenchyma and portal tracts of normal livers, and in those where the histological diagnosis was non-specific reactive hepatitis or acute liver injury. In precirrhotic and cirrhotic livers nerves in portal tracts and fibrous septae remained prominent, but the parenchymal innervation was reduced in precirrhotic livers and was absent from regenerating nodules in established cirrhosis. The causes and functional consequences of this parenchymal denervation in cirrhosis remain to be established.

Antibodies, Monoclonal↗
PubMed1992

Changes in intracellular free calcium concentration during long exposures to simulated ischemia in isolated mammalian ventricular muscle.

Intracellular free calcium concentration ([Ca2+]i) was measured in isolated ferret ventricular papillary muscles during and after long exposures to ischemia. All experiments were performed at 37 degrees C, and the muscles were stimulated at 1 Hz. Ischemia was simulated by changing from superfusion with oxygenated Tyrode's solution to superfusion with water-saturated gas (95% N2-5% CO2), thus simultaneously stopping oxygenation and restricting the extracellular space. [Ca2+]i was measured with aequorin, which was microinjected into superficial cells of the preparation. Exposure to ischemia caused a complex series of changes in [Ca2+]i. In the first few minutes the changes in [Ca2+]i were variable; however, after approximately 5 minutes all preparations exhibited a progressive increase in amplitude and duration of the stimulated rise in [Ca2+]i (the calcium transient). The amplitude of the calcium transients peaked after approximately 18 minutes of ischemia, when they were 339% of the control value. After this peak, the calcium transients progressively failed to occur in response to stimulation and declined in amplitude; simultaneously, spontaneous oscillations of [Ca2+]i appeared and increased in size and frequency. The oscillations in turn then gradually became less frequent until a large, prolonged (5-10 minute) increase in [Ca2+]i occurred, after which [Ca2+]i returned to a low level. There were no further oscillations after this event, which was seen on average after 37 minutes of ischemia. A slowly progressive contracture often began to develop at about this time. A gradual rise in resting [Ca2+]i occurred during the remainder of the exposure to ischemia. When muscles were reperfused after long exposures to ischemia, there was a very large and prolonged increase in [Ca2+]i, which was usually associated with a contracture and failure of recovery of developed tension. The large increase in [Ca2+]i could be reduced by the inclusion of 3 mM nickel chloride in the reperfusing solution. Comparison between reperfusion with O2 gas versus reperfusion with anoxic Tyrode's solution indicated that reoxygenation was more beneficial to the muscle than resumption of bulk flow. These results reveal the complex spectrum of changes in [Ca2+]i that occur during ischemia and on reperfusion. These changes in [Ca2+]i are likely to play an important role in the generation of ischemic arrhythmias and muscle damage.

Animals↗
PubMed1992

Role of excitation-contraction coupling in muscle fatigue.

The force produced by muscles declines during prolonged activity and this decline arises largely from processes within the muscle. At a cellular level the reduced force could be caused by: (a) reduced intracellular calcium release during activity; (b) reduced sensitivity of the myofilaments to calcium; or (c) reduced maximal force development. Experiments involving intracellular calcium measurements in isolated single fibres show that all 3 of the above contribute to the decline of force during fatigue. Metabolic changes associated with fatigue are probably involved in each of the 3 factors. Thus the accumulation of phosphate and protons which occur during fatigue cause a reduction in calcium sensitivity and a decline in maximal force. The cause of the reduced intracellular calcium during contractions in fatigue is less clear. During prolonged tetani the conduction of the action potential in the T-tubules appears to fail leading to reduced intracellular calcium in the central part of the muscle fibre. However, during repeated tetani there is a uniform decline of intracellular calcium across the fibre and this remains one of the least understood processes which contribute to fatigue.

Action Potentials↗
PubMed1992

Molecular cloning and characterization of the major endothelin receptor subtype in porcine cerebellum.

Endothelin receptors (ETRs) display subtype heterogeneity and are widely distributed throughout the tissues of the periphery and central nervous system. In order to gain further insight into the potential molecular differences of ETRs, we initiated molecular cloning of ETR genes by screening for the appearance of 125I-ET-1 binding activity in COS cells transfected with pools of a porcine cerebellum cDNA expression library. Two independent clones (pPCETR 1.1 and pPCETR 5.6) were identified and isolated by repeated rounds of pool enrichment and COS cell expression. DNA sequence analysis of pPCET 1.1 and pPCET 5.6 indicated that both clones have the same nucleotide sequence; the deduced amino acid sequence indicated that the porcine cerebellum ETR is 443 residues in length and consists of seven potential transmembrane domains, with homology to members of the GTP-binding protein-coupled receptor superfamily. Northern analysis indicated a single mRNA species of about 5 kilobases, which is expressed significantly in cerebellum, lung, kidney, and pituitary. Expression of functional receptor was demonstrated by endothelin-1 (ET-1)-mediated Ca2+ mobilization in COS cells transfected with pPCETR 1.1 (COS/ETR 1.1) and ET-1-mediated electrophysiological responses in Xenopus oocytes injected with RNA derived from pPCETR 1.1. Quantitative comparison of saturation binding of 125I-ET-1 to either porcine cerebellum or COS/ETR 1.1 membranes indicated an identical apparent dissociation constant. The relative efficacy of ET-related peptides to compete for binding of 125I-ET-1 to receptor from porcine cerebellum and COS/ETR 1.1 indicated that both preparations encode a nonselective or ETBR subtype. Chemical cross-linking of 125I-ET-1 to receptor derived from cerebellum or COS/ETR 1 revealed two bands, with apparent molecular masses of 47 and 35 kDa. These data demonstrate that the pPCETR 1.1 encodes the major ETR subtype in the porcine cerebellum.

Amino Acid Sequence↗
PubMed1991

Uraemia: is urea more important than we think?

Urea is accumulated as an osmolyte by some groups of animals even though it impairs protein function. These organisms can withstand high internal urea concentrations because they also accumulate other low-molecular-weight osmolytes, the methylamines, which can offset the effects of urea on proteins. Methylamines have also been found in the medulla of the mammalian kidney (where urea concentrations are high) and in the plasma of human subjects with chronic renal failure. These findings suggest that previous investigations of the potential contribution of urea to the syndrome of uraemia may have been confounded because of the presence of variable concentrations of protective substances. That naturally occurring methylamines or related substances may prove to have a useful therapeutic role in uraemia is also possible.

Animals↗
PubMed1991

Okadaic acid, a protein phosphatase inhibitor, increases the calcium transients in isolated ferret ventricular muscle.

Okadaic acid is a protein phosphatase inhibitor which has been found to produce a marked positive inotropic effect in isolated cardiac muscle. Using aequorin-injected ferret papillary muscles, we demonstrate that the increase in tension seen with okadaic acid is accompanied by a simultaneous increase in the amplitude of the calcium transients. By comparison with the effects of changing the extracellular calcium concentration, it is shown that the increase in calcium transient amplitude can account for the inotropic effect of okadaic acid.

Animals↗
PubMed1979

Anaesthesia.

Explore the source record for details and available documents.

Anesthesia, Intravenous↗
PubMed1979

Effect of age on incidence of breast cancer in females.

Incidence and mortality data on breast cancer in females from various Occidental (Western) and Japanese populations were analyzed. After adjustment for birth cohort and year of event, the age curves from all the Western populations were very similar in shape. The age curve for Osaka incidence was very similar in shape to the Western incidence curves. The Osaka curve continued to increase after menopause; the postmenopausal decrease in rates in individual cross sections was the result of a strong cohort effect. The premenopausal mortality curve for Japan was very similar in shape to the Western curves; however, the postmenopausal Japanese mortality curve had a smaller slope at each point.

Adult↗
PubMed1979

The influence of age, year of birth, and date on mortality from malignant melanoma in the populations of England and Wales, Canada, and the white population of the United States.

The age-adjusted death rates from malignant melanoma of the skin have increased from 1951 to 1975 by about 3% per year in the populations of England and Wales, Canada, and the white population of the US. This is due to large increases in risk of successively later born cohorts. Any effects of earlier diagnosis of improved treatment within the period 1951--1975 have been sufficiently steady to fail to alter these trends. The slope of the log rates with log age is about 3.5. Projections of rates for at least the next decade can be made with some confidence, and provide a basis for evaluating control measures.

Adult↗
PubMed1979

Alteration of cartilage glycosaminoglycan protein acceptor by somatomedin and cortisol.

The effect of somatomedin and cortisol on embryonic chick cartilage in vitro indicates that somatomedin stimulates 35SO4 uptake while cortisol decreases it with no effect on glycosaminoglycan turnover. Xylosyltransferase activity is increased in crude fractions of somatomedin-treated cartilage but decreased in cortisol-treated cartilage. By using a Smith-degraded proteoglycan as an exogenous acceptor, xylosyltransferase activities from both treatments were equivalent, suggesting that the enzyme was not rate limiting. The results of xylosyltransferase assays conducted by mixing enzyme and endogenous acceptor from control, cortisol-treated and somatomedin-treated cartilage, suggest both effects to be at the level of the acceptor protein.

Animals↗