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Biomedical subjects

H Yao

Publications and source records attributed to H Yao.

At least 109 records · Page 6Linked to original sources
PubMed1998

[The content of estradiol receptors in oral mucosa precancerous lesions and its effect]

OBJECTIVE:In order to clarify the content of estroen receptors (ER) in oral mucosa precancerous lesions and its effect on dignosis and treatment. METHODS: ER was measured by SP method in 19oral squamous cell carcinoma (SCC),20 oral leukoplakia(LK),21 oral lichen planus (LP) and 7 normal mucosa(NM). RESULTS: 42.86%,71.43%,60.00%,68.42% were ER positive in NM,LP,LK,SCC respectively. The postitive cells located in spinous layer.ER contents were no significance different in these four diseases.There was no relationship between ER content and pathologic staging. CONCLUSION: It showed that ER existed in SCC,LK,LP and NM,but it could not implicate for the carcinogenesis.Oral mucousal tumor is perhaps hormone depended.

Journal Article↗
PubMed1997

AMPA receptor antagonist, YM90K, reduces infarct volume in thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

We examined the effects of a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptor, YM90K, on brain infarction using a newly developed stroke model of thrombotic distal middle cerebral artery occlusion. Male spontaneously hypertensive rats (5-7 months old) were subjected to photochemically-induced distal middle cerebral artery occlusion as previously described [Stroke 26 (1996) 333-336]. Intravenous infusion of YM90K (n = 8) (5 mg/kg per h for 1 h) or the same amount of vehicle (n = 8) (alkaline saline) was started 5 min after distal middle cerebral artery occlusion. Penumbral cerebral blood flow was determined with laser-Doppler flowmetry. Three days after the ischemic insult, brains were stained with 2,3,5-triphenyltetrazolium chloride and infarct volumes were determined. One hour infusion of YM90K significantly reduced infarct volume by 34% (93 +/- 23 mm3 in control group vs. 61 +/- 25 mm3 in YM90K-treated group, P = 0.017). There were no significant differences in the degrees of cerebral blood flow reduction after distal middle cerebral artery occlusion between the YM90K treated and control groups. YM90K reduces infarct volume in experimental ischemia produced by photothrombotic distal middle cerebral artery occlusion in rats. The present results demonstrated beneficial effects of AMPA receptor blockade on acute ischemic stroke.

Animals↗
PubMed1997

cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway.

Cyclic adenosine monophosphate (cAMP) has tissue-specific effects on growth, differentiation, and gene expression. We show here that cAMP can activate the transcription factor Elk-1 and induce neuronal differentiation of PC12 cells via its activation of the MAP kinase cascade. These cell type-specific actions of cAMP require the expression of the serine/threonine kinase B-Raf and activation of the small G protein Rap1. Rap1, activated by mutation or by the cAMP-dependent protein kinase PKA, is a selective activator of B-Raf and an inhibitor of Raf-1. Therefore, in B-Raf-expressing cells, the activation of Rap1 provides a mechanism for tissue-specific regulation of cell growth and differentiation via MAP kinase.

Animals↗
PubMed1997

Diversity associated with the second expressed HLA-DRB locus in the human population.

Although diversity within the HLA-DRB region is predominantly focused in the DRB1 gene, the second expressed DRB loci, DRB3, DRB4, and DRB5, also exhibit variation. Within DRB1(*)15 or DRB1(*)16 haplotypes, four new variants were identified: 1) two new DRB5 alleles, DRB5*0104 and DRB5*0204, 2) a haplotype carrying a DRB1(*)15 or *16 allele without the usual accompanying DRB5 allele, and 3) a haplotype carrying a DRB5(*)0101 allele without a DRB1(*)15 or *16 allele. The evolutionary origins of these haplotypes were postulated based on their associations with the DRB6 pseudogene. Within HLA haplotypes which carry DRB3, a new DRB3(*)0205 allele and one unusual DRB3 association were identified. Finally, two new null DRB4 alleles are described: DRB4(*)0201N, which exhibits a deletion in the second exon, and a second allele, DRB4(*)null, which lacks the second exon completely. Gene conversion-like events and variation in the number of functional genes through reciprocal recombination and inactivation contribute to the diversity observed in the second expressed HLA-DRB loci.

Alleles↗
PubMed1997

Age-related changes in the DNA and RNA content of the brain in spontaneously hypertensive rats.

To elucidate the effects of aging accompanied with hypertension on brain nucleic acid, we measured both the DNA and RNA contents of six specific brain regions in adult (5-6 months old) and aged (18-22 months old) female spontaneously hypertensive rats (SHRs). Although no statistical difference was observed in the RNA content, the DNA content did tend to increase in the hippocampal CA1 of aged SHR (4.24 +/- 0.55 ng/microgram protein, mean +/- SD, n = 6) in comparison to that of adult SHR (3.21 +/- 0.71 ng/microgram protein, n = 4). Hence, aged SHRs showed a significant decrease in the RNA to DNA ratio in the CA1 subfield of the hippocampus (3.79 +/- 0.61) compared to adult SHR (5.27 +/- 0.81). On the other hand, no other regions, except for the dorsolateral region of the striatum, showed any difference in the RNA/DNA ratio between aged and adult SHR. We therefore conclude that subtle changes in the nucleic acid occur in vulnerable regions of the brain in aged SHRs.

Aging↗
PubMed1997

Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice.

The mechanism by which mutations in the presenilin (PS) genes cause the most aggressive form of early-onset Alzheimer's disease (AD) is unknown, but fibroblasts from mutation carriers secrete increased levels of the amyloidogenic A beta 42 peptide, the main component of AD plaques. We established transfected cell and transgenic mouse models that coexpress human PS and amyloid beta-protein precursor (APP) genes and analyzed quantitatively the effects of PS expression on APP processing. In both models, expression of wild-type PS genes did not alter APP levels, alpha- and beta-secretase activity and A beta production. In the transfected cells, PS1 and PS2 mutations caused a highly significant increase in A beta 42 secretion in all mutant clones. Likewise, mutant but not wildtype PS1 transgenic mice showed significant overproduction of A beta 42 in the brain, and this effect was detectable as early as 2-4 months of age. Different PS mutations had differential effects on A beta generation. The extent of A beta 42 increase did not correlate with presenilin expression levels. Our data demonstrate that the presenilin mutations cause a dominant gain of function and may induce AD by enhancing A beta 42 production, thus promoting cerebral beta-amyloidosis.

Alzheimer Disease↗
PubMed1997

Photochemically induced colonic ischaemic lesions: a new model of ischaemic colitis in rats.

BACKGROUND: Recent clinical studies suggest that ischaemic colitis is caused by a microcirculatory disturbance that involves thrombosis of the colon. AIM: To establish a new model of photochemically induced ischaemic colitis in rats. METHODS: Thirty male Wistar rats were anaesthetised with amobarbital, the femoral veins were cannulated and laparotomies were performed. The serosal surface of the proximal colon was irradiated by using a krypton laser (wavelength 568 nm, 20 mW) for four minutes. An intravenous infusion of a photosensitising dye, rose bengal (20 mg/kg body weight), was administered over 90 seconds, beginning at the start of irradiation. Rats were killed immediately (n = 4), 12 hours (n = 2), 24 hours (n = 10), three days (n = 4), seven days (n = 4), 14 days (n = 2), or 28 days (n = 2) after irradiation. Two control rats received laser irradiation without dye infusion. Specimens of the irradiated sites were examined by using histopathology. RESULTS: Localised ulcers of the colon were present in rats killed at 12 hours, 24 hours, three days, and seven days after irradiation. Microscopy findings were consistent with the features of human ischaemic colitis. Reproducible ulcerative lesions were produced by photothrombosis of microvessels in the colon. CONCLUSION: This model may be useful for further investigation of the pathophysiology of ischaemic colitis.

Animals↗
PubMed1997

An ATP-sensitive potassium channel activator reduces infarct volume in focal cerebral ischemia in rats.

ATP-sensitive potassium channels are activated under hypoxic or ischemic conditions. The effects of ATP-sensitive potassium channel activators on cerebrovasculature and cerebral blood flow (CBF) are not well understood. We examined the effect of the ATP-sensitive potassium channel activator Y-26763 on focal cerebral ischemia in rats. In 24 spontaneously hypertensive rats, either Y-26763 (24 micrograms/kg) or vehicle was given by intracarotid infusion over 60 min, starting 30 min before photochemically induced thrombotic occlusion of the middle cerebral artery. CBF was measured by laser-Doppler flowmetry in the peri-ischemic penumbral cortex. Although Y-26763 lowered systemic blood pressure by 13 mmHg, the infarct volume assessed 3 days after the occlusion was significantly smaller in the Y-26763-treated group (n = 12, 71.2 +/- 22.0 mm3) than in the control group (n = 12, 94.7 +/- 20.4 mm3, P = 0.013). Y-26763 did not affect CBF before or after occlusion compared with CBF values of the control group. The results are consistent with the view that the activation of the ATP-sensitive potassium channel is neuroprotective in focal cerebral ischemia.

Adenosine Triphosphate↗
PubMed1997

[CT for diagnosis of parathyroid adenoma].

We analyzed Ct findings of 10 cases with parathyroid adenoma which had been verified by surgery and pathologic section. The correct localization of 9 adenomas was made by CT preoperatively. The method of CT scanning of parathyroid adenoma were elucidated. The results showed that most adenomas were located in the groove between trachea and esophagus. The contour of tumors was oval, the edge was smooth and regular. Enhancement CT images were helpful for differentiating the tumor from blood vessel. It is indicated that CT scanning is a good method for localizing the parathyroid adenoma.

Adenoma↗
PubMed1997

[Role of Na+/Ca2+ exchange blocker in rat hippocampal injury during anoxia].

Effects of Na+/Ca2+ exchange blocker, Benzamil, on rat hippocampal slices and on cultured hippocampal neuronal [Ca2+]i (intracellular free Ca2+ concentration) during anoxia were investigated by means of microelectrode recording technique and laser scanning confocal microscope respectively. The results showed that the PV sustained time of hippocampal slices pretreated with Benzamil (50 mumol) after anoxia was markedly longer than that of control, suggesting that inhibition of Na+/Ca2+ exchange can delay the irreversible injury to hippocampal cells. Moreover, by using a confocal microscope we found that acute anoxia induced a rapid increase of [Ca2+]i in hippocampal neurons and this could be significantly attenuated by 20 mumol Benzamil. All these results indicate that Na+/Ca2+ exchanger is involved in the anoxic injury to rat hippocampus and it may be one of the major ways leading to the anoxia-induced [Ca2+]i increase of hippocampal neurons.

Amiloride↗
PubMed1997

[The effect of arsenic on reproduction and offspring development of rats].

The effect of arsenic on reproduction and offspring development of Wistar rats was studied. The results demonstrated that the pregnant rate and feeding survival rate in high dose group were lower than these of in the groups of control and low dose. The differences of normal parturition rate and the survival rate in all the groups were not significant. The contents of arsenic in the young rats were increased by the doses of arsenic and the differences were significant. After 10, 20 and 30 days of birth, the weight of offspring in high dose group was lighter than that in the groups of control and low dose. According to the results, arsenic can affect the reproduction of rats and the development of their offspring.

Animals↗
PubMed1997

Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate cancers and is inversely related to apoptosis.

Several oncogenes involved in prostate carcinogenesis activate mitogen-activated protein (MAP) kinases, which can relay both proliferative (via extracellular regulated kinases (ERK)) and apoptotic signals (via jun N-terminal protein kinases (JNK)) to the nucleus. Mitogen-activated protein kinase phosphatase 1 (MKP-1) is induced by several oncogenes in the ras-dependent pathway and can inactivate both MAP kinase pathways. The role of MKP-1 in proliferation and apoptosis is, however, still controversial. A series of 51 prostate cancers, including a subset (n = 13) that had been previously treated by androgen ablation, was used to examine whether MKP-1 mRNA and protein expression correlated with that of ERK-1, JNK-1, bcl-2, which confers resistance to apoptosis, and apoptotic index measured by in situ end-labeling of fragmented DNA. In a subset of tumors, MKP-1 expression was assessed by semiquantitative RT-PCR and was compared with both ERK-1 and JNK-1 enzymatic activity. In cases not treated by androgen ablation, MKP-1 was overexpressed in the preinvasive stage of prostate cancer, but its expression decreased with higher histologic grade and advanced disease stage. There was coexpression of MKP-1, ERK-1, and JNK-1 proteins. In addition, MKP-1 expression was inversely correlated to JNK-1 but not to ERK-1 enzymatic activity. Finally, MKP-1 and bcl-2 were inversely related to apoptotic indices. In cases treated by total androgen ablation, MKP-1 and bcl-2 were both down-regulated, whereas JNK-1 was up-regulated. Subpopulations of cells that did not undergo apoptosis maintained expression of both MKP-1 and bcl-2. These results suggest that MKP-1 overexpression is associated with the early phases of neoplastic transformation in prostate tissue. The enzymatic data on MKP-1 kinase substrates and the inverse correlation between MKP-1 and parameters of programmed cell death support the hypothesis that MKP-1 inhibits apoptosis in human prostate tumors, perhaps through the JNK pathway.

Apoptosis↗
PubMed1997

Effects of basic fibroblast growth factor on the differentiation, growth, and viability of a new human medulloblastoma cell line (UM-MB1).

We presently report the effects of human recombinant basic fibroblast growth factor (bFGF) on a newly established medulloblastoma cell line, UM-MB1. This predominantly adherent cell line has a mean doubling time of 39.3 hours and was found, by karyotypic analysis, to be near triploid. UM-MB1 consists of undifferentiated cells expressing markers of neuronal lineage such as the three neurofilament subunits as well as neuron-specific enolase, synaptophysin, and microtubule-associated proteins 1 and 5. In contrast, no immunoreactivity for glial fibrillary acidic protein was evident. When exposed to nanomolar amounts of bFGF, UM-MB1 cells began to extend neurite-like processes with arborizations and growth-cone-like structures. In addition, UM-MB1 cells treated with bFGF exhibited ultrastructural alterations that reflect their enhanced differentiation as well as the increased expression of at least one of the neurofilament subunits as evidenced both immunocytochemically and on Western blots. Furthermore, bFGF significantly decreased UM-MB1 cell growth as well as induced their death. UM-MB1 cells treated with bFGF for several days displayed DNA cleavage, nuclear shrinkage, and chromatin condensation while retaining their cytoplasmic and mitochondrial membrane integrity, all early indices of apoptosis. After this, cell death was evident with the concomitant appearance of the classical apoptotic bodies. By flow cytometry, bFGF was found to increase the proportion of cells in G1 before inducing their death by apoptosis. In conclusion, UM-MB1 cells can, when appropriately stimulated, be induced to differentiate along their neuronal lineage pathway. Their differentiation induced by bFGF, although incomplete, appears to promote or inhibit the expression of apoptotic effectors or suppressors in these cells, respectively, so to induce their death by an apoptotic-like mechanism.

Antigens, Differentiation↗
PubMed1997

[Effect of adenosine on intracellular free calcium in cultured rat hippocampal CA1 neurons during anoxia].

Intracellular free Ca2+ concentration ([Ca2+]i) was measured by laser scanning confocal microscope, using Ca2+ indicator Fluo-3 in cultured hippocampal CA1 neurons isolated from newborn rat. The results showed that acute anoxia induced a rapid increase of [Ca2+]i in hippocampal CA1 neurons, and this increase could be attenuated by 100 mumol/L adenosine significantly. This effect of adenosine could be suppressed by adenosine A1 receptor antagonist CPT or potassium channel blockers, 4-AP and glipizide. These results suggest that adenosine activates 4-AP- or ATP-sensitive potassium channels through A1 receptors, and consequently inhibits the [Ca2+]i elevation in hippocampal neurons during anoxia.

Adenosine↗
PubMed1996

Amlodipine, a Ca2+ channel antagonist, modifies cerebral blood flow autoregulation in hypertensive rats.

We measured the cerebral blood flow at rest and during hemorrhagic hypotension in 7 rats of each group using laser-Doppler flowmetry. Simultaneously, the absolute baseline cerebral blood flow values in the parietal cortex were quantified with the hydrogen clearance method. Baseline mean arterial pressure was significantly lowered, by 29 mm Hg, in the amlodipine-treated group, while the baseline cerebral blood flow was 36 +/- 4 ml/100 g/min (mean +/- S.D.) which was almost the same as the 40 +/- 5 in the control group. The lower limits of the cerebral blood flow autoregulation, defined as the mean arterial pressure at which the cerebral blood flow decreased by 10% of the baseline value, were shifted to a lower level of 107 +/- 9 mm Hg in the treated group compared with 133 +/- 5 mm Hg in the control (P < 0.001). The results demonstrated that, in hypertensive rats with amlodipine treatment, cerebral perfusion was preserved at a lower blood pressure level, which is advantageous under hypotensive conditions.

Amlodipine↗
PubMed1996

Metabolically programmed polyamine analogue antidiarrheals.

The design, synthesis, and testing of a novel class of antidiarrheal drugs based on a tetraamine pharmacophore are reported. While N1,N14-diethylhomospermine (DEHSPM) (5 mg/kg) completely prevents diarrhea in rodents, tissue distribution studies demonstrated that the principal metabolite of DEHSPM, homospermine (HSPM), accumulates and persists in tissues for a protracted period of time. This accumulation accounts for a large part of the chronic toxicity of DEHSPM. Thus a major objective was to develop a metabolically labile analogue of DEHSPM which retained the desirable biological properties of the parent drug. Hydroxyl groups, sites vulnerable to further metabolic transformation, were introduced into the external aminobutyl segments providing N1,N14-diethyl-(3R),(12R)-dihydroxyhomospermine [(HO)2-DEHSPM]. The design concept was assisted by molecular modeling, which predicted that (HO)2DEHSPM would have a Ki for polyamine transport essentially identical with that of DEHSPM. The experimentally measured Ki and also the observed values of other biological properties of (HO)2DEHSPM were in fact identical with those of DEHSPM, including IC50 against L1210 cells, impact on the NMDA receptor, and impact on L1210 native polyamine pools. Most significantly, however, there was no accumulation of the dideethylated metabolite in tissues from mice treated chronically with (HO)2DEHSPM, and (HO)2DEHSPM was 3-fold less toxic than DEHSPM. Finally, (HO)2DEHSPM completely prevented diarrhea in the castor oil-treated rat model at a dose of 5 mg/kg, just as did DEHSPM.

Animals↗