Biomedical subjects
Publications and source records attributed to L Luo.
Following a significant decrease in pain threshold (PT) in the carrageenin injected paw of rat, the PT of the contralateral uninjected paw was usually increased but might also be significantly decreased or unchanged. These three directions of PT change in the contralateral non-inflamed paws were found to be correlated with the magnitude of decrease in PT in the inflamed sides.
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A recombinant baculovirus carrying the gag gene but lacking the protease coding sequences of human immunodeficiency virus type 2 (HIV-2) has been constructed. When this recombinant baculovirus is used to infect insect cells, a high level of gag precursor protein, gag pr41, is expressed. Electron microscopy showed that the majority of gag pr41 was budding through the plasma membrane and being released into the culture medium in spherical virus-like particles with a diameter of approximately 100 nm. Metabolic labeling demonstrates that gag pr41 is myristylated. Our results demonstrated that HIV-2 gag pr41 can be assembled into virus-like particles in the absence of other HIV proteins. Rabbits immunized with purified gag pr41 particles produced high-titer antibody and Western blot analysis showed that anti-gag pr41 rabbit sera recognize p17, p24, and p55 gag proteins of HIV-1. These results show that gag pr41 particles are highly immunogenic and that gag proteins of HIV-1 and HIV-2 have similar antigenic epitopes.
The role of substance P (SP) in the regulation of sympathetic outflow to the cardiovascular system was assessed. Intrathecal injection(ith) of capsaicin caused a release of SP from the spinal cord and resulted in an increase in blood pressure and heart rate accompanied by an elevation of plasma adrenaline and noradrenaline. This pressor response was blocked by ith SP antagonist D-Pro2, D-Phe7, D-Trp9-SP or antiserum against SP. The immunohistochemical study showed that the SP-like immunoreactivity in T-8 of the spinal cord was decreased as the amount of capsaicin administrated was increased. Spinal cord transection had no effect on pressor responses caused by ith 10 micrograms capsaicin. These results suggest that SP transmits excitatory information to the cardiovascular system via spinal sympathetic pathway.
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The long-term sequelae of vasectomy were studied in a retrospective cohort study of 4596 vasectomized and 4340 nonvasectomized farmers from eight rural communes in Sichuan, People's Republic of China. The mean duration since the operation was 14.5 years with a range of 10 to 25 years. At the time of evaluation the vasectomized men were generally healthier than the non-vasectomized for a wide range of health indicators including clinical signs of cardiovascular disease, resting ECG changes, positive ECG changes following a maximal stress test, or fundus abnormalities. The lack of association between vasectomy and cardiovascular disease noted in Europe and the USA is supported by the present study conducted in a population with a low prevalence of cardiovascular disease and risk factors.
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Recent studies from our and other laboratories have shown that Leydig cells, the testicular cells responsible for testosterone production; become steroidogenically hypofunctional with age. Herein we review some of what we now know about the mechanisms by which this occurs, and some among the many remaining uncertainties in our understanding of Leydig cell aging. To help shed light on how Leydig cells age, we also briefly discuss the regulation of Leydig cell differentiation during puberty and of Leydig cell function in adult animals.
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Primary points of control in steroidogenesis are the transport of cholesterol from intracellular stores to the inner mitochondrial membrane, and the subsequent conversion of cholesterol to pregnenolone by the cholesterol side-chain cleavage enzyme (P450scc). Testosterone production has been shown to decline in Brown Norway rat Leydig cells as the rats age. To better understand the mechanism by which aging Leydig cells lose steroidogenic function, we examined the effect of aging on steroidogenic acute regulatory protein (StAR), an important Leydig cell cholesterol transfer protein, and on P450scc. Leydig cells isolated from middle-aged (14 months) and old (24 months) rats produced significantly less testosterone than cells from young (4 months) rats. StAR mRNA (1.7 kilobase [kb]) was significantly reduced in Leydig cells from middle-aged and old rats, by 26% and 52%, respectively. Significant reductions also were seen in the steady-state levels of mRNA for P450scc, of 29% and 50%, respectively. Western blots revealed significant reductions in StAR protein, by 47% and 74%, respectively, and in P450scc protein, by 38% and 54%, respectively. In response to LH stimulation in vitro, testosterone production by Leydig cells in young, middle-aged, and old rats increased by 30-, 40-, and 33-fold, respectively, although the amounts of testosterone produced by the young cells significantly exceeded that produced by the middle-aged and old cells. StAR protein also increased in response to LH by 1.4- , 3-, and 11-fold, respectively, whereas P450scc protein remained unchanged. These results are consistent with the conclusion that compromise of StAR-mediated cholesterol transport may play a key role in age-related reductions in Leydig cell steroidogenesis. However, because P450scc is reduced in old Leydig cells, the reaction catalyzed by this enzyme would be rate-limiting under circumstances in which saturating amounts of cholesterol entered the mitochondria.
Previous studies have shown that the ability of Brown Norway rat Leydig cells to produce testosterone declines significantly with age. To address the possible mechanism(s) by which aging Leydig cells lose steroidogenic function, we determined the effect of age on the steady-state levels of the mRNAs for the steroidogenic enzymes P450 cholesterol side-chain cleavage (P450scc), delta 5-3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD), and 17 alpha-hydroxylase/C17-20 lyase (P450(17) alpha), and on the levels of immunoreactive steroidogenic enzyme proteins and enzyme activities. Northern blot analysis revealed that the levels of P450scc and P450(17) alpha mRNAs in Leydig cells isolated from the testes of aged (22-month-old) Brown Norway rats were reduced from their levels in young (4-month-old) rats, but that 3 beta-HSD mRNA was not reduced. Western blot analysis, however, revealed that cellular levels of each of the P450scc, P450(17) alpha, and 3 beta-HSD proteins were reduced with aging. The activities of the steroidogenic enzymes, assessed by incubating Leydig cells in culture with substrate and then summing all steroidogenic reaction products through testosterone, similarly revealed that P450scc, 3 beta-HSD, P450(17) alpha, and additionally 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), were all reduced with aging. We conclude that age-related loss of steroidogenic function results at least in part from reductions in the levels and activities of each of the steroidogenic enzymes responsible for converting cholesterol to testosterone, and not by differential regulation of these enzymes.