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H Yao

Publications and source records attributed to H Yao.

At least 127 records · Page 7Linked to original sources
PubMed1996

L-arginine does not improve cortical perfusion or histopathological outcome in spontaneously hypertensive rats subjected to distal middle cerebral artery photothrombotic occlusion.

The potential of nitric oxide (NO) to influence positively or negatively the outcome of mechanically induced focal cerebral ischemia is still controversial. Recent evidence suggests that NO of vascular origin, whether synthesized from exogenously administered L-arginine (L-Arg) or from NO donor compounds, is beneficial but that of neuronal origin is not. However, the therapeutic potential of NO to ameliorate stroke induced by arterial thrombosis has not been reported. We assessed the therapeutic effect of L-Arg administration in spontaneously hypertensive rats (SHR) subjected to permanent photothrombotic occlusion of the distal middle cerebral artery (dMCA). The ipsilateral carotid artery was left unligated to enhance L-Arg delivery into the putative penumbral region. Local CBF (LCBF) was assessed at 30 min by the [14C]iodoantipyrine technique (n = 9), while histological infarct volumes and index of peripheral ischemic cell change were determined at 3 days (n = 7). Rats (n = 9) given 300 mg/kg L-Arg at 18 and 3 h before photothrombotic dMCA occlusion and at 5 min afterward displayed no significant differences in LCBF compared with animals (n = 8) injected with water (the carrier vehicle) and similarly irradiated. Infarct volumes were also similar, being 37.0 +/- 9.7 mm3 (SD) in the vehicle-treated and 49.1 +/- 17.2 mm3 (SD) in the L-Arg-treated groups (both n = 7), as were assessments of ischemic neuronal density in the penumbra. In contrast, L-Arg administered intravenously in a dose of 300 mg/kg to nonischemic SHR (n = 5) increased cortical CBF by approximately 75% during a 70-min observation period. We conclude that thrombotic processes superimposed upon cerebral ischemia may facilitate tissue reactions that offset the potentially beneficial effect of L-Arg, and this caveat must be considered when proposing L-Arg for clinical treatment of focal thrombotic stroke.

Animals↗
PubMed1996

Simplified model of krypton laser-induced thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: The effects of thrombotic occlusion of the middle cerebral artery on compromised ischemic tissue may be different from and more severe than those of cerebral ischemia induced by mechanical occlusion of the artery. Photothrombosis, which is based on photochemical damage to the endothelium and subsequent platelet aggregation, is an efficient method to induce thrombosis in vivo. This study aimed to improve and simplify this unique method for an ischemia model of middle cerebral artery occlusion in rats. METHODS: Male spontaneously hypertensive rats (5 to 6 months old, 300 to 450 g) were anesthetized with halothane, endotracheally intubated, and mechanically ventilated. A krypton laser operating at 568 nm was used to irradiate the exposed distal middle cerebral artery with an intact dura above the rhinal fissure. The photosensitizing dye rose bengal (20 mg/kg body wt) was administered intravenously over 90 seconds starting simultaneously with 4 minutes of laser irradiation at a power of 20 mW to cause thrombotic occlusion of this artery. RESULTS: The irradiated middle cerebral artery was completely occluded by intraluminal thrombi within 3 minutes after simultaneous laser irradiation and rose bengal infusion. Thrombosed materials were not stained by phosphotungstic acid-hematoxylin stain (ie, aggregated platelets lacked apparent fibrin). The mean volume of 3-day-old infarction, indicated by the lack of staining with 2,3,5-triphenyltetrazolium chloride, was 84.8 +/- 17.4 mm3 (mean +/- SD, n = 6). CONCLUSIONS: We demonstrated a reproducible and minimally traumatic model of brain infarction induced by the thrombotic distal middle cerebral artery occlusion in rats.

Animals↗
PubMed1996

Detection of PML-RAR alpha in patients with APL during follow-up period.

OBJECTIVE: To evaluate the significance of PML-RAR alpha transcripts in patients with acute promyelocytic leukemia (APL) during remission period and to follow up the patients through monitoring aberrant gene expression. PATIENTS AND METHODS: This study included 17 patients with APL (5 females and 12 males). Another 19 APL patients during relapse served as control. RNA extraction was obtained through the single-step method. By means of reverse transcriptase polymerase chain reaction (PCR), the PML-RAR alpha was detected in the sample mRNA. RESULTS: Nine out of 10 patients with complete remission (CR) duration shorter than 3 years were positive. Four cases became negative and three remained positive among 7 cases in a long remission of over 3 years. The difference of the positive rate of PML-RAR alpha transcripts between the 2 groups was significant (P < 0.05). Four among 12 positive cases relapsed. No evidence of relapse was present in the 5 negative patients after 9.6 +/- 3.9-month follow-up. Further treatment was therefore given to the 4 positive patients whose treatment was already ceased at that time. By this management they were all in CR during the following 10-month observation. CONCLUSIONS: RT-PCR detection for PML-RAR alpha transcripts was useful in monitoring MRD and guiding further treatment to obtain a long remission. Persistently positive transcripts were closely associated with the relapse.

Adolescent↗
PubMed1996

Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis.

Many mitogens and human oncogenes activate extracellular regulated kinases (ERKs), which in turn convey proliferation signals. ERKs or mitogen-activated protein (MAP) kinases are inactivated in vitro by MAP kinase phosphatases (MKPs). The gene encoding one of these MKPs, MKP-1, is a serum-inducible gene and is transcriptionally activated by mitogenic signals in cultured cells. As MKP-1 has been shown to block DNA synthesis by inhibiting ERKs when expressed at elevated levels in cultured cells, it has been suggested that it may act as a tumor suppressor. MKP-1 mRNA and MAP kinase (ERK-1 and -2) protein expression was assessed in 164 human epithelial tumors of diverse tissue origin by in situ hybridization and immunohistochemistry. MKP-1 was overexpressed in the early phases of prostate, colon, and bladder carcinogenesis, with progressive loss of expression with higher histological grade and in metastases. In contrast, breast carcinomas showed significant MKP-1 expression even when poorly differentiated or in late stages of the disease. MKP-1, ERK-1, and ERK-2 were co-expressed in most tumors examined. In a subset of 15 tumors, ERK-1 enzymatic activity as well as structural alterations that might be responsible for loss of function of MKP-1 during tumor progression, were examined. ERK-1 enzymatic activity was found to be elevated despite MKP-1 overexpression. No loss of 5q35-ter (containing the MKP-1 locus) was detected by polymerase chain reaction in metastases compared with primary tumors. Finally, no mutations were found in the catalytic domain of MKP-1. These data indicate that MKP-1 is an early marker for a wide range of human epithelial tumors and suggest that MKP-1 does not behave as a tumor suppressor in epithelial tumors.

Biomarkers, Tumor↗
PubMed1996

Diagnosis and treatment of nephrotic syndrome during pregnancy.

OBJECTIVE: To set forth the methods of diagnosis and treatment of nephrotic syndrome during pregnancy (NSP) so as to decrease perinatal mortality. MATERIALS AND METHODS: Forty cases of NSP including 5 twins in Tianjin Central Hospital of Obstetrics and Gynecology in the past 13 years have been reviewed, and the diagnosis and treatment were compared between group A (1979-1990, 23 cases) and group B (1991-1992, 17 cases). RESULTS: NSP occurred before the 20th gestational week in 15% of cases and the patient's condition was serious. Clinically, NSP was classified into three types: simple, nephritis and pregnancy induced hypertension (PIH) type. The perinatal maternal and fetal prognosis was poor. Complications occurred in 27.5% of patients. One patient died from eclampsia and disseminated intravascular coagulation (DIC). The total perinatal mortality was 42.22%, with group A (27 babies including 4 twins), 51.86% (14/27), and group B (18 babies including 1 twin), 27.78% (5/18) (P < 0.01). CONCLUSIONS: NSP is a result of reproductive immunology and belongs to type III allergic reaction in terms of immunology. Early diagnosis, early treatment and timely termination of pregnancy may improve the outcome.

Adult↗
PubMed1995

The alpha 1-adrenoceptor antagonist, doxazosin, modulates the lower limit of autoregulation of cerebral blood flow during hemorrhagic hypotension in anesthetized hypertensive rats.

The objective of the present study was to examine the effects of administration of an alpha 1-adrenoceptor antagonist, doxazosin, for 7 days on cerebral blood flow and the autoregulatory response to hypotension in anesthetized spontaneously hypertensive rats. We determined the cerebral blood flow at rest and during hemorrhagic hypotension in 14 rats of each group using laser-Doppler flowmetry, and at the same time, the absolute baseline cerebral blood flow values at the parietal cortex were also quantified in some of the rats with the hydrogen clearance method. Baseline mean arterial pressure was significantly lowered, by 41 mm Hg, in the doxazosin-treated group, while the baseline cerebral blood flow was 31 +/- 4 ml/100 g/min(mean +/- S.D.) which was almost the same as the 32 +/- 5 ml/100 G/min in the control group. The lower limits of cerebral blood flow autoregulation were 139 +/- 9 mm Hg in the control group and 96 +/- 12 mm Hg in the treated group; the difference was significant (P < 0.001). The present results demonstrated that the lower limit of cerebral blood flow autoregulation shifts to a lower level after chronic treatment with doxazosin, an effect which is favorable for the maintenance of cerebral blood flow under hypotensive conditions.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

Cyclic adenosine monophosphate can convert epidermal growth factor into a differentiating factor in neuronal cells.

The rat pheochromocytoma (PC12) cell line is a model for studying the mechanism of growth factor action. Both epidermal growth factor and nerve growth factor stimulate mitogen-activated protein (MAP) kinase in these cells. Recent data suggest that the transient activation of MAP kinase may trigger proliferation, whereas sustained activation triggers differentiation in these cells. We have tested this model by asking whether agents that stimulate MAP kinase without inducing differentiation can act additively to trigger differentiation. Neither forskolin nor epidermal growth factor can stimulate differentiation, yet both activate MAP kinase in these cells. Together, their actions on MAP kinase are synergistic. Cells treated with both agents differentiate, measured morphologically and by the induction of neural-specific genes. We propose that cellular responses to growth factor action are dependent not only on the activation of growth factor receptors by specific growth factors but on synchronous signals that may elevate MAP kinase levels within the same cells.

Adrenal Gland Neoplasms↗
PubMed1995

A novel mitogen-activated protein kinase phosphatase. Structure, expression, and regulation.

Mitogen-activated protein (MAP) kinase lies at the convergence of various extracellular ligand-mediated signaling pathways. It is activated by the dual-specificity kinase, MAP kinase kinase or MEK. MAP kinase inactivation is mediated by dephosphorylation via specific MAP kinase phosphatases (MKPs). One MKP (MKP-1 (also known as 3CH134, Erp, or CL100)) has been reported to be expressed in a wide range of tissues and cells. We report the identification of a second widely expressed MKP, termed MKP-2, isolated from PC12 cells. MKP-2 showed significant homology with MKP-1 (58.8% at the amino acid level) and, like MKP-1, displayed vanadate-sensitive phosphatase activity against MAP kinase in vitro. Overexpression of MKP-2 in vivo inhibited MAP kinase-dependent gene transcription in PC12 cells. MKP-2 differed from MKP-1 in its tissue distribution and in its extent of induction by growth factors and agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions.

Amino Acid Sequence↗
PubMed1995

Isradipine, a calcium channel blocker, attenuates the ischemia-induced release of dopamine but not glutamate in rats.

This study was designed to investigate the role of the L-type voltage sensitive calcium channel blocker, isradipine, in the ischemia-induced release of neurotransmitters. Male spontaneously hypertensive rats were subjected to cerebral ischemia for 60 min by bilateral carotid artery occlusion, and recirculated for 120 min. Isradipine (0.25 mg/kg n = 6) or vehicle (n = 6) was administered subcutaneously at 20 min before ischemia. In the striatum, cerebral blood flow was determined by the hydrogen clearance method and concentrations of extracellular dopamine and glutamate were measured by in vivo brain dialysis technique. Extracellular dopamine in the vehicle-treated group increased by 180-fold from the basal level, and glutamate by 24-fold during cerebral ischemia. Isradipine significantly attenuated the ischemic release of dopamine to 33-34% (P < 0.05) of the vehicle group, while it did not affect glutamate release. It is suggested that the release mechanism of dopamine and glutamate during cerebral ischemia may be different, especially in the dependence on the L-type calcium channels.

Animals↗
PubMed1995

Ischemia-induced release of amino acids in the hippocampus of aged hypertensive rats.

We have recently demonstrated the age-related vulnerability of hippocampal neurons to 20-min forebrain ischemia in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of aging on the release of amino acids in the hippocampus during transient cerebral ischemia for 20 min. Concentrations of extracellular amino acids and cerebral blood flow in the CA1 subfield were examined by an in vivo brain dialysis technique and a hydrogen clearance method, respectively, in adult (5-7 month) and aged (19-23 month) female SHR. During cerebral ischemia by bilateral carotid artery occlusion, cerebral blood flow to the hippocampus decreased to 20% of the resting values in both groups. After recirculation, both groups showed delayed hypoperfusion which was more prominent in the aged SHR. In the adult rats, concentrations of both aspartate and glutamate increased to approximately 8-fold of the resting values during ischemia. The elevation of these excitatory amino acids in the adult SHR was not significantly different from that in the aged rats. In contrast, the concentration of taurine increased 26-fold in the adult SHR but only 16-fold in the aged rats. Changes in other amino acids were not different between the two groups. These results indicate that an imbalance of excitatory and inhibitory amino acids, e.g., smaller release of taurine, during ischemia may, at least in part, contribute to the age-related vulnerability of hippocampal neurons to transient cerebral ischemia in SHR.

Aging↗
PubMed1995

Local cerebral glucose utilization and cytoskeletal proteolysis as indices of evolving focal ischemic injury in core and penumbra.

To ascertain the tempo of progression to irreversible injury in focal ischemia, we subjected halothane-anesthetized Sprague-Dawley rats to photochemically induced distal middle cerebral artery occlusion (dMCAO) combined with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Head temperature was maintained at 36 degrees C. At times centered at either 1.5 or 3 h post-dMCAO, the rate of local glucose metabolism (lCMRgl) was measured by 2-deoxyglucose autoradiography, and cytoskeletal proteolysis was assessed regionally by an immunoblotting procedure to detect spectrin breakdown products. At 1.5 h (n = 5), the cortical ischemic core was already severely hypometabolic (lCMRgl 15.5 +/- 10.8 mumol 100 g-1 min-1, mean +/- SD), whereas the cortical penumbral zone was hypermetabolic (69.0 +/- 9.7). (The lumped constant was verified to be unchanged by methylglucose studies). Neutral red pH studies at this time point showed that both the core and penumbral zones were equally acidotic. By 3 h post-dMCAO (n = 6), lCMRgl in the penumbral zone had fallen to low levels (15.4 +/- 2.2 mumol 100 g-1 min-1) equal to those of the ischemic core (16.7 +/- 4.5). Correspondingly, spectrin breakdown in the ischemic core was advanced at both 2 and 3.5 h post-dMCAO (36 +/- 18% and 33 +/- 18% of total spectrin, respectively), whereas in the penumbral zone spectrin breakdown was less extensive and more highly variable at both times (22 +/- 23% and 29 +/- 16%). We conclude that irreversible deterioration of the ischemic core, as evidenced by the onset of local cytoskeletal proteolysis, begins within 2 h of middle cerebral artery occlusion. In the ischemic penumbra, the transition from glucose hyper- to hypometabolism occurs by 3.5 h and is associated with a milder and more variable degree of spectrin breakdown.

Animals↗