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Biomedical subjects

J H Zhang

Publications and source records attributed to J H Zhang.

At least 19 recordsLinked to original sources
PubMed2003

Analysis of cytokine regulators inducing interferon production by mouse uterine natural killer cells.

In mice and women, terminal differentiation of uterine natural killer (uNK) cells commences during endometrial decidualization. Both proliferation and interferon (IFN)-gamma are induced. Uterine NK cell precursors appear to home from secondary lymphoid organs to decidualizing uteri and localize mesometrially to the central decidua basalis, the site of maternal arterial modification at Gestation Days (gd) 9.5-10. In mice, genetic absence of uNK cells results in absence of pregnancy-induced spiral artery modification. Administration of IFN-gamma to uNK-negative pregnant females induces arterial modifications without fetal loss. In this study, we investigated the roles of cytokines, known in other tissues to differentiate and activate NK cells, in induction of IFN-gamma production in normal mouse implantation sites. Fecundity evaluation, implantation site morphometry, and IFN-gamma quantification in interleukin (IL)-12p40(0/0), IL-18(0/0), dual IL-12p40(0/0)/IL-18(0/0) and congenic strains revealed the importance of both IL-12 and IL-18 in the induction of spiral artery modification and IFN-gamma synthesis. Immediately after implantation, IL-18 was localized transiently to decidual cells, but by gd8, IL-18 was produced solely by uNK cells, suggesting that early uNK cells are activated by stroma and lymphocyte-derived signals maintain later uNK cell activation. Mesometrial tissue of C57Bl/6J mice was examined by reverse transcription polymerase chain reaction assay in virgin, early postimplantation, and midgestation females for expression of the heterodimeric cytokines IL-23 (composed of IL-12p40 and a novel alpha chain), IL-27 (composed of two IL-12-related chains) and IL-27R. No expression was detected in virgin uteri. The four genes were induced by gd6, and uNK cells isolated from midgestation transcribed IL-23alpha and IL-27R. This study advances the understanding of uNK cell activation during normal pregnancy.

Animals↗
PubMed2002

Upregulation of small GTPase RhoA in the basilar artery from diabetic (mellitus) rats.

The goal of this study was to determine whether RhoA, a small GTPase, might be involved in the development of cerebral pathogenesis in diabetes. Male SD rats (n = 120) were divided into six groups: diabetic for 2, 4, 8 weeks, and an age-matched control group. Diabetes was induced by intravenous injection of streptozotocin (50 mg/kg). RhoA mRNA expression in basilar artery was measured by competitive RT-PCR. RhoA mRNA level was significantly increased in 4 weeks (184.1 +/- 28.5%, n = 7) and 8 weeks (218.7 +/- 24.5%, n = 7) after STZ injection compared to the age matched control basilar arteries (P < 0.05). Western blot was used to measure the membrane binding RhoA level to represent the activity of RhoA. We found that RhoA activity was strikingly increased in the diabetic basilar artery (n = 10 in each groups) compared to control basilar artery after STZ injection. Our data demonstrated that there was an upregulation of RhoA in the basilar artery of STZ induced diabetic rats, suggesting that RhoA might be involved in the cerebral vascular pathogenesis during diabetes mellitus.

Animals↗
PubMed2002

Role of MAPK in chronic cerebral vasospasm.

This study was undertaken to investigate the role of p44/42 MAPK in a dog double hemorrhage model of subarachnoid hemorrhage (SAH), and whether MEK inhibitors can alter the degree of SAH-induced vasoconstriction. The diameter of the basilar artery, which was compared with day 0 angiogram, decreased gradually in a time-dependent manner from day 3 (80%), day 5 (68%) through day 7 (53.5%). The level of MAPK (p44/42) immunoprecipitation peaked on day 3 and remained enhanced through day 7 (P < 0.05). MEK inhibitor PD98059 significantly reduced p44/42 MAPK immunoprecipitation and significantly reversed vasospasm and increased residual diameter to 79.0% on day 7. These results demonstrated that p44/42 MAPK kinase is involved in the pathogenesis of cerebral vasospasm. The MEK inhibitor PD98059 might be useful in the treatment of vasospasm.

Animals↗
PubMed2002

Na(+)/Ca(2+) exchanger expression in the developing rat cortex.

The Na(+)/Ca(2+) exchanger (NCX) participates in the regulation of neuronal Ca(2+) homeostasis and is also believed to be involved in the neuronal responses to hypoxia. However, there are very limited data on how NCX mRNA and protein expression are regulated during brain development. In the present study, we sought to elucidate the developmental expression of NCX1 and NCX2 in the rat cortex from late fetal to adult stages using reverse transcription-polymerase chain reaction and western blot assays. The primers for NCX1 mRNA targeted the alternative splicing domain to allow differentiation between NCX1 splice variants. Our results show that: (1) only two NCX1 mRNA splice variants (NCX1.5 and NCX1.4) are present in the cortex and their expression is age-dependent; (2) total NCX1 mRNA levels are low in fetal tissue, reach maximum density at postnatal day 8 and substantially decline with further maturation; (3) NCX2 mRNA density is significantly greater than total NCX1 mRNA for all ages and increases markedly during maturation from fetus/neonate to adult; and (4) NCX1 protein expression is lowest in late fetal cortex and reaches maximum levels after 2 weeks postnatally, even though expression levels are not significantly different between newborn and adult animals. Also, we found a similar NCX1 protein trend in the subcortical and cerebellar regions during development. From these data we suggest that NCX1 and NCX2 are differentially expressed in the cortex with a predominance of NCX2 levels during postnatal development. We speculate that the developmental increase in NCX2 expression is responsible for the overall increase in Na(+)/Ca(2+) exchange capacity during maturation.

Aging↗
PubMed2002

Optimum ratio of histidine in the piglet ideal protein model and its effects on body metabolism. I. Basal diet formulation based on digestible amino acids according to the ideal protein model for 10 to 20 kg piglets.

A 4 x 4 Latin square design was used to determine ileal apparent digestibility of amino acids (AAs) in corn, soybean meal, feather meal and dried whey in young pigs. The data were then to be used in formulating a basal diet for studies on AA metabolism in young pigs. Eight castrates T-cannulated at terminal ileum (average initial body weight 12.5 +/- 0.62 kg) were divided into 4 groups on the basis of body weight and transferred to individual metabolism crates. They were then fed four experimental diets containing the four feedstuffs to be tested (corn, soybean meal, feather meal and dried whey). The trial lasted 20 days, which included 4 five-day periods for ileal digesta collection. It was found that the digestibility of the AAs was similar to that reported in literature. Based on the findings a basal diet for this research was formulated according to an ideal protein model for the 10 to 20 kg piglet, on the basis of digestible AAs and containing 14.13 MJ/kg digestible energy, 18.22% crude protein, 1.04% digestible lysine and 0.23% digestible histidine.

Amino Acids↗
PubMed2002

Optimum ratio of histidine in the piglet ideal protein model and its effects on the body metabolism. II. Optimum ratio of histidine in 10-20 KG piglet ideal protein and its effects on blood parameters.

Two growth trails were conducted to determine the optimum ratio of histidine in 10-20 kg piglet ideal protein model. Four diets containing 0.23%, 0.31%, 0.39% and 0.47% digestible histidine (0, 0.08%, 0.16%, 0.24% crystalline histidine supplemented into the basal diet) were fed to 96 piglets of mean initial body weight 10.3 +/- 1.08 kg for 18 d in Experiment 1. Average daily gain, average daily feed intake and feed conversion efficiency were inhibited (P < 0.05) with the diet containing 0.23% digestible histidine. Performance was maximized with 0.31% digestible histidine. As the dietary histidine increased, blood urea nitrogen and serum cholesterol concentration were influenced significantly. The concentrations of serum histamine and free histidine did not change with increase in digestible histidine from 0.23 to 0.31%, but higher supplementation resulted in a significant linear increase in both serum parameters. It was concluded that the dietary level of 0.23% digestible histidine does not meet the requirement of 10-20 kg piglets. Based on the results from Experiment 1, Experiment 2 was designed to determine the optimum ratio of lysine:histidine in the ideal protein model of 10-20 kg piglet. Ninety-six Large White x Landrace piglets weighing 10.2 +/- 0.88 kg were divided into 4 groups. They were fed four diets containing 0.26, 0.29, 0.32 or 0.35% digestible histidine, formulated by adding 0.03, 0.06, 0.09 or 0.12% crystalline histidine to the basal diet. The trial lasted for 21 days. Results showed that performance was significantly improved with 0.32 and 0.35% digestible histidine. As dietary histidine increased, blood urea nitrogen tended to decrease but not significant at P < 0.05. Serum cholesterol concentration increased with an increase in dietary histidine level and reached a maximum at 0.35%. Serum histamine increased with increasing dietary histidine. Free serum histidine increased linearly with increased dietary histidine. From both experiments it was concluded that the digestible histidine requirement for 10-20 kg piglets was 0.31% and that the optimum ratio of dietary lysine to histidine should be 100:30. The concentrations of cholesterol, histamine and free histidine in serum were sensitive parameters to measure changes in dietary histidine levels.

Amino Acids↗
PubMed2001

Effect of hyperbaric oxygen on striatal metabolites: a microdialysis study in awake freely moving rats after MCA occlusion.

We have shown that hyperbaric oxygen (HBO) reduced cerebral infarction in rat middle cerebral artery occlusion model (MCAO). The present study was undertaken to evaluate the effect of HBO on ischemic striatal metabolites at different times after MCAO and reperfusion. A rat MCAO model was produced via the intraluminal filament method. After 2 h of occlusion the suture was removed and reperfusion was allowed. The rats were sacrificed at 24 h after reperfusion. HBO treatment was administered by putting rats in the HBO chamber at 3 atmospheres absolute (ATA) HBO for 1 h. Glucose, lactate, pyruvate, and glutamate in striatal extracellular fluid were collected and measured by a microdialysis system at 7, 10, and 24 h after reperfusion. Glucose, pyruvate and glutamate concentrations were increased after reperfusion. HBO treatment decreased glucose, pyruvate, and glutamate almost to the control level (preocclusion level). The lactate concentration remained unchanged after ischemic/reperfusion and after HBO treatment. This study suggested that altered brain energy metabolites and excitatory amino acids occurred during cerebral ischemia and and HBO regulated these striatal metabolites, which might contribute to the protective effect of HBO in cerebral ischemia.

Animals↗
PubMed2001

Ceramide blocks PDGF-induced DNA synthesis in mesangial cells via inhibition of Akt kinase in the absence of apoptosis.

The mechanism of action of ceramide in glomerular mesangial cells has not been studied. We investigated the effect of C2 ceramide on the mitogenic signal transduction pathways induced by PDGF in mesangial cells. Increasing concentrations of C2 ceramide inhibited PDGF-induced DNA synthesis in a dose-dependent manner with maximum inhibition at 15 microM. This inhibition of DNA synthesis was associated with attenuation of PDGF-induced early response gene c-fos transcription. PDGF receptor beta immunecomplex kinase assay showed no inhibitory effect of C2 ceramide on PDGF receptor tyrosine kinase activity. We have recently shown that the mitogenic effect of PDGF is mediated by the enzyme phosphatidylinositol (PI) 3 kinase in mesangial cells. C2 ceramide had no effect on PDGF-induced PDGFR-associated PI 3 kinase activity. These data indicate that inhibitory effect of C2 on PDGF-induced DNA synthesis is likely due to post-receptor and post-PI 3 kinase events. To address the mechanism of C2-mediated inhibition of DNA synthesis, we investigated the downstream target of PI 3 kinase, Akt. PDGF time-dependently increased Akt kinase activity in a PI 3 kinase-dependent manner. Incubation of mesangial cells with C2 ceramide inhibited PDGF-induced Akt activity. Akt kinase inhibits apoptosis of cells via phosphorylation of multiple proapoptotic proteins. However, inhibition of Akt activity by C2 ceramide did not induce apoptosis in mesangial cells. These data provide the first evidence that in mesangial cells, ceramide cross-talks with PI 3 kinase-dependent Akt kinase to inhibit PDGF-induced DNA synthesis without inducing apoptosis.

Animals↗
PubMed2001

Effect of prolonged hypoxia on Na+ channel mRNA subtypes in the developing rat cortex.

Voltage-gated Na+ channels are regulated in response to oxygen deprivation in the mammalian cortex. Past investigations have demonstrated that Na+ channel protein expression is up-regulated in the immature brain exposed to prolonged hypoxia. Since it is unknown as to which Na+ channel subtype(s) is involved in this regulation, we used RT-PCR to assess the effect of hypoxia on Na+ channel I, II and III alpha-subunit mRNA expression in the developing rat cortex. Na+ channel II mRNA tended to increase during early development, whereas Na+ channel I and III did not change or slightly decreased with age. Hypoxic exposure for 1-day had no effect on Na+ channel expression, while 5-day hypoxia significantly increased Na+ channel III density, with a slight increase in Na+ channel I and no appreciable change in Na+ channel II. These results suggest that Na+ channel subtype expression in the developing cortex is differentially regulated in response to prolonged hypoxic exposure.

Animals↗
PubMed2001

Orexin (hypocretin)-like immunoreactivity in the cat hypothalamus: a light and electron microscopic study.

Orexin-A-like immunoreactive (OrA-ir) neurons and terminals in the cat hypothalamus were examined using immunohistochemical techniques. OrA-ir neurons were found principally in the lateral hypothalamic area (LHA) at the level of the tuberal cinereum and in the dorsal and posterior hypothalamic areas. In the LHA the majority of the neurons were located dorsal and lateral to the fornix; a small number of OrA-ir neurons were also present in other regions of the hypothalamus. OrA-ir fibers with varicose terminals were detected in almost all hypothalamic regions. The high density of fibers was located in the suprachiasmatic nucleus, the infundibular nucleus (INF), the tuberomamillary nucleus (TM) and the supra- and pre-mamillary nuclei. Ultrastructural analysis revealed that OrA-ir neurons in the LHA receive abundant input from non-immunoreactive terminals. These terminals, which contained many small, clear, round vesicles with a few large, dense core vesicles, made asymmetrical synaptic contacts with OrA-ir dendrites, indicating that the activity of orexin neurons is under excitatory control. On the other hand, the terminals of OrA-ir neurons also made asymmetrical synaptic contact with dendrites in the LHA, the INF and the TM. The dendrites in the LHA were both non-immunoreactive and OrA-ir; conversely, the dendrites in the INF and the TM were non-immunoreactive. In these regions, OrA-ir terminals contained many small, clear, round vesicles with few large, dense core vesicles, suggesting that orexinergic neurons also provide excitatory input to other neurons in these regions.

Animals↗
PubMed2001

Oxyhemoglobin produces apoptosis and necrosis in cultured smooth muscle cells.

Confluent rat aortic smooth muscle cells were treated with OxyHb in a concentration- and time-dependent manner. A high concentration of OxyHb (100 microM) within 24 h decreased cell density. DNA analysis showed a smear pattern characteristic of cell necrosis. Transmission electron microscopy demonstrated disintegration of the cell membrane and destruction of cell organelles. Western blotting using PARP antibody revealed that 116 kDa PARP was not cleaved to 85 kDa, an apoptosis-related fragment. On the contrary, a low concentration of OxyHb (10 microM) produced apoptotic cell death at 72 h that was supported by DNA analysis and TUNEL staining. These results demonstrated that a high level of OxyHb induced necrosis within 24 h and a low concentration of OxyHb produced apoptosis after 72 h in cultured smooth muscle cells. Morphological alterations induced by OxyHb might contribute to the vascular wall changes in the cerebral arteries following subarachnoid hemorrhage (SAH).

Animals↗
PubMed2001

Nuclear localization of G protein beta 5 and regulator of G protein signaling 7 in neurons and brain.

The role that Gbeta(5) regulator of G protein signaling (RGS) complexes play in signal transduction in brain remains unknown. The subcellular localization of Gbeta(5) and RGS7 was examined in rat PC12 pheochromocytoma cells and mouse brain. Both nuclear and cytosolic localization of Gbeta(5) and RGS7 was evident in PC12 cells by immunocytochemical staining. Subcellular fractionation of PC12 cells demonstrated Gbeta(5) immunoreactivity in the membrane, cytosolic, and nuclear fractions. Analysis by limited proteolysis confirmed the identity of Gbeta(5) in the nuclear fraction. Subcellular fractionation of mouse brain demonstrated Gbeta(5) and RGS7 but not Ggamma(2/3) immunoreactivity in the nuclear fraction. RGS7 and Gbeta(5) were tightly complexed in the brain nuclear extract as evidenced by their coimmunoprecipitation with anti-RGS7 antibodies. Chimeric protein constructs containing green fluorescent protein fused to wild-type Gbeta(5) but not green fluorescent fusion proteins with Gbeta(1) or a mutant Gbeta(5) impaired in its ability to bind to RGS7 demonstrated nuclear localization in transfected PC12 cells. These findings suggest that Gbeta(5) undergoes nuclear translocation in neurons via an RGS-dependent mechanism. The novel intracellular distribution of Gbeta(5).RGS protein complexes suggests a potential role in neurons communicating between classical heterotrimeric G protein subunits and/or their effectors at the plasma membrane and the cell nucleus.

Amino Acid Sequence↗
PubMed2001

Age-related RhoA expression in blood vessels of rats.

Aging is a major risk factor for the development of vascular diseases that lead to stroke and heart failure. Several cellular factors such as cell adhesion, motility, contractile response, and cytokinesis are involved in the aging process. RhoA, a member of the Rho family, plays a primary role in the regulation of these cellular factors. This study aims to investigate whether RhoA is involved in these age-related responses to vascular change. We found that in older rats (19 months ole), RhoA mRNA increased 1.9-fold in the aortic arteries and 2.4-fold in the basilar arteries compared to the younger rats (2 months old). Membrane binding, but not cytosol RhoA, levels were found to significantly increase in the aortic and basilar arteries with age, which suggests that RhoA activity increases in older rats. Staining of RhoA increased markedly with age in both the medial and endothelial layers of the collected aortic and basilar arteries. These results show that RhoA expression and activity in the aortic and basilar arteries increased as a function of age, thereby suggesting that RhoA might be altered in the vascular response change of aged rats.

Aging↗
PubMed2001

Age-related changes in P2 receptor mRNA of rat cerebral arteries.

Aging alters the vascular response to extracellular nucleotides. However, the molecular mechanisms that underlie the effect of aging remain unclear. We investigated the mRNA expression of P2X(1), P2Y(1), P2Y(2) subtypes of the nucleotide receptors (P2) in the basilar artery, aorta and carotid artery from male Sprague-Dawley rats, 2-months and 19-months old. In the basilar arteries of 19-month old rats, as compared to the 2-month old rats, the P2X(1) receptor transcripts were reduced and the P2Y(1) and P2Y(2) receptor mRNA was increased. In the aorta and carotid arteries, P2Y(1) receptor mRNA was decreased in the 19-month old rats when compared to the 2-month old rats. There were no marked changes of P2X(1) and P2Y(2) receptor mRNA between the two age groups in the aorta or carotid artery. In endothelial cells, P2Y(1) and P2Y(2) receptor mRNA was reduced with age. We concluded that, down-regulation of P2X(1) and up-regulation of P2Y(1), P2Y(2) receptor mRNA in smooth muscle cells and down-regulation of P2Y(1) and P2Y(2) receptor mRNA on vascular endothelial cells might underlie the changes of cerebral vascular tone in aging.

Aging↗