Biomedical subjects

S M Zhu

Publications and source records attributed to S M Zhu.

At least 37 records · Page 2Linked to original sources

PubMed1993

[Role of nucleus accumbens in cardiovascular activities and its relationship with opioid peptides in rats].

In this study, electrical stimulation and microinjection in nucleus accumbens in urethane-anesthetized rats were conducted to observe the effect of electrical stimulation of nucleus accumbens on blood pressure and heart rate. The following results were observed: (1) Electrical stimulation of the nucleus accumbens of rat resulted in significant hypotension and bradycardia. (2) Kainic acid microinjected into the nucleus accumbens, could abolish the effects mentioned above. (3) Naloxone administered to the nucleus accumbens could block the cardiovascular inhibitory effect evoked by electrical stimulation of nucleus accumbens. The intra-accumbens injection of mu-receptor agonist, DAGO could also elicit hypotension and bradycardia to an extent comparable to that of the effect due to electrical stimulation, whereas kappa-receptor agonist, U-50 had no such an effect. (4) When the cardiovascular inhibitory effect elicited by electrical stimulation of the nucleus accumbens was observed, the discharge activity in locus ceruleus was also decreased. (5) Bilateral vagotomy could abolish the change in heart rate elicited by the electrical stimulation of nucleus accumbens, but not the hypotension. It is suggested that the mu-opioid receptors of neurons in nucleus accumbens are involved in cardiovascular activity.

Animals↗

PubMed1992

The intrastriatal 6-hydroxydopamine model of hemiparkinsonism: quantitative receptor autoradiographic evidence of correlation between circling behavior and presynaptic as well as postsynaptic nigrostriatal markers in the rat.

Unilateral injections of 6-hydroxydopamine into the striatum resulted in almost immediate ipsilateral amphetamine (AMPH)- and delayed contralateral apomorphine (APO)-induced circling behavior in rats. APO-induced rotation correlated positively with that caused by AMPH. In these animals, there was an almost complete disappearance of dopamine uptake sites as well as increases in DA D2 receptors in specific subdivisions of the ipsilateral caudate-putamen (CPu). Both the rate of AMPH- and APO-induced rotation correlated with the percentage of DA terminal loss in the total aspect and in various quadrants of the striatum. In contrast, AMPH- and APO-induced rotation correlated with the percentage increase in striatal D2 receptors only in the dorsolateral (DL) aspect of the CPu. These results indicate that both AMPH- and APO-induced rotation can be used to determine the extent of DA terminal loss in the rat basal ganglia. The positive correlation of circling behavior to only changes in DA D2 receptors observed in the DL striatal subdivision provides further evidence for the heterogeneity of the basal ganglia. This model of hemiparkinsonism in the rat which uses a distant intrastriatal approach to the destruction of nigral DA cell bodies may be a more appropriate model to study the regenerative properties of the nigrostriatal DA system. This approach could also be used to more specifically localize peptidergic receptors on midbrain dopamine cell bodies.

Amphetamine↗

PubMed1992

p53 mutation and protein accumulation during multistage human esophageal carcinogenesis.

Preinvasive lesions of squamous cell carcinoma are well defined morphologically and provide a model for multistage carcinogenesis. Since alterations in the p53 tumor suppressor gene occur frequently in invasive esophageal squamous cell carcinoma, we examined a set of preinvasive lesions to investigate the timing of p53 mutation. Surgically resected tissues from nine patients with esophageal squamous cell carcinoma contained precursor lesions which had not yet invaded normal tissues. Immunohistochemistry showed high levels of p53 protein in both preinvasive lesions and invasive carcinomas in six cases; sequence analysis of all invasive tumors identified p53 missense mutations in two cases. Preinvasive lesions from both tumors with mutations plus one wild-type tumor were microdissected and sequenced. In one patient there were different mutations in the invasive carcinoma (codon 282, CGGarg > TGGtrp) and a preinvasive lesion (codon 272, GTGval > T/GTGleu/val). In a second case, an invasive carcinoma had a mutation in codon 175 (CGCarg > CAChis), and adjacent preinvasive lesions contained a wild-type sequence. A carcinoma and preinvasive lesion from the third case contained high levels of protein and a wild-type DNA sequence. Therefore, p53 mutation may precede invasion in esophageal carcinogenesis, and multifocal esophageal neoplasms may arise from independent clones of transformed cells. The timing of p53 protein accumulation is favorable for an intermediate biomarker in multistage esophageal carcinogenesis.

Base Sequence↗

PubMed1992

Quantitative in situ hybridization evidence for differential regulation of proenkephalin and dopamine D2 receptor mRNA levels in the rat striatum: effects of unilateral intrastriatal injections of 6-hydroxydopamine.

Nigrostriatal (NS) dopaminergic (DA) neurons are thought to exert an inhibitory influence on striatal enkephalinergic systems through their DA D2 receptors. In order to investigate the effects of partial lesions of the NS DA on striatal proenkephalin (PEK) and D2 receptor mRNAs, animals were allocated to High, Intermediate, and Low rotators on the basis of amphetamine-induced rotation observed after intrastriatal injections of 6-hydroxydopamine (6-OHDA). On the ipsilateral side of the lesions, there were significant increases in PEK mRNA in the total aspect of the caudate-putamen (CPu) of the High (+204%), the Intermediate (+125%), and of the Low (+67%) rotation groups in comparison to controls; these changes correlated positively with increases in rotation rate. Unexpectedly, there were also significant increases in striatal PEK mRNA on the contralateral side although these changes were much less prominent than those observed on the side of the lesions. Conversely, only the High rotation group showed significant increases (+112%) in D2 receptor mRNA which occurred only on the lesioned side. Interestingly, the low rotation group actually showed some non-significant decreases (-25%) on the side of the lesions. These results indicate that partial lesions of the NS DA projections are sufficient to cause substantial increases in PEK mRNA but not in D2 receptor mRNA. These data also provide evidence that the two nigrostriatal DA projections and the systems which they modulate might be under interdependent sets of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Implantation of genetically modified mesencephalic fetal cells into the rat striatum.

Transplantation of dopamine (DA) cells into the rat model of hemiparkinsonism induced by intranigral 6-hydroxydopamine (6-OHDA) injections has so far focused mainly on DA replacement via a pump-like mechanism. In the present study, we employed a model of hemiparkinsonism that uses an intrastriatal approach to lesioning the nigrostriatal DA pathway to assess the possibility of using cell transplantation to cause regeneration of that system. Toward that end, we transplanted two types of cells on the side of the 6-OHDA-induced lesions: 1) nonmodified fetal mesencephalic cells and 2) fetal mesencephalic cells that have been infected with a retrovirus vector containing a PKC beta 1 cDNA. Both types of cells cause behavioral improvement although the changes were more prominent and occurred earlier in the PKC-modified groups. Tyrosine hydroxylase (TH) immunocytochemistry revealed significantly cell survival in both groups of animals; in situ hybridization studies confirmed the continuous expression of TH mRNA in both groups. Interestingly, long TH-positive axons were observed only in the striata of animals implanted with PKC-modified cells. More importantly, surviving endogenous nigral TH-positive cell bodies were found only on the lesioned side in the latter group. The observations in these animals were associated with significantly smaller decreases in [3H]mazindol-labeled DA uptake sites in both the striata and substantia nigra pars compacta on the side ipsilateral to the 6-OHDA-induced lesions. Furthermore, immunohistochemical studies revealed increased gliosis in the striata of animals grafted with the PKC-modified cells. When taken together, these results indicate that transplantation of normal fetal mesencephalic cells can cause behavioral improvement by providing DA to the host striata whereas PKC-modified cells can, in addition, prevent the progressive degeneration of or cause regeneration of the dying nigrostriatal DA neurons in this model of hemiparkinsonism. These results are discussed in terms of their support for a role for second messenger systems and glial cells, as well as extracellular matrix molecules in the regeneration of the CNS.

Amphetamine↗

PubMed1991

Intrastriatal implants of fetal mesencephalic cells attenuate the increases in striatal proenkephalin mRNA observed after unilateral 6-hydroxydopamine-induced lesions of the striatum.

Unilateral injections of 6-hydroxydopamine (6-OHDA) cause significant bilateral increases in striatal proenkephalin (PEK) mRNA in rat brain. We have tested the possibility that implantation of fetal mesencephalic cells can normalize these changes. Two types of grafts were used: 1) embryonic day-15 mesencephalic cells and 2) embryonic day-15 cells which have been modified with a retroviral vector containing a cDNA for protein kinase C (PKC). At two months after grafting, both cell types cause significant attenuation of the increases which occurred on the side of the lesion. However, only the PKC-modified cells cause normalization of the changes on the contralateral side. These observations indicate that, in addition to normalizing supersensitive striatal dopamine (DA) D2 receptors, embryonic cells can also attenuate the alterations in PEK mRNA observed after lesions of the nigrostriatal DA system. The finding that the PKC-modified cells caused bilateral effects in the striatum suggests that second messenger systems may play a role in the bilateral improvement reported in parkinsonian patients who had gotten unilateral intrastriatal transplants.

Animals↗

PubMed1991

Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer.

A strategy and methods for archival analysis of genetic and protein alterations in the p53 tumor-suppressor gene are presented. The tumor series includes 43 paraffin-embedded esophageal carcinomas from two high-incidence regions in the People's Republic of China. More than half contained elevated p53 protein levels which were detected by a high-titer polyclonal antiserum and a sensitive immunohistochemical method. To estimate the frequency of underlying mutations, DNA was isolated from conventional paraffin sections, amplified by the polymerase chain reaction, and examined by dideoxy termination sequencing. Analysis of exons 5-8 in a subset of 10 tumors revealed mis-sense point mutations in 4 out of 5 immunostain-positive tumors and a mutation encoding a stop codon in 1 of 5 immunostain-negative tumors. In this report of archival material, we conclude that detectable levels of p53 protein correlate closely with the occurrence of mis-sense mutations. Furthermore, these methods render large repositories of paraffin-embedded tumor and non-tumor tissues accessible to analysis. Immunohistochemical screening for elevated protein levels followed by sequence analysis represents an efficient strategy for the evaluation of the p53 mutational spectrum.

Adenocarcinoma↗

PubMed1990

Long-term culture of human esophageal explants and cells.

Human esophageal epithelium obtained from intermediate autopsies (less than 12 h) was maintained as cell and explant cultures. In order to develop a serum-free, defined media culture model, several medias and additives were evaluated. The viability and differentiation of the epithelial cells cultured with serum-free, Keratinocyte Growth Media (KGM, Clonetics Co., San Diego, CA) was improved over that of esophageal cells and explants cultured in either serum-supplemented CMRL 1066 (OCM), serum-free additive-supplemented CMRL 1066, or cimetidine-supplemented CMRL 1066. The KGM component EGF was determined to be trophic for esophagus cells on the basis of findings of increased 3H-TdR labelling in KGM cultures when compared to control cells grown in KGM without EGF (KBM). The morphologic pattern of the cytoskeletal proteins actin, keratin, and vimentin were characterized in isolated cell populations. The intermediate filaments, keratin, and vimentin were co-expressed in these epithelial cells. Esophageal explant viability, differentiation, and outgrowth from 15 cases were also evaluated in dishes coated with basement membrane associated proteins. Explants cultured in these dishes were equally well-preserved and differentiated. There were no significant differences in the explant histology when there was protein coating of the culture dishes, although one case showed improved outgrowth with laminin coating. A main advantage for using this culture system is that the same medium (KGM) can be used for both the culture of explants and isolated epithelial cells. Future applications of this model include determining: (1) the effect different concentrations of EGF and calcium in the media will have on esophageal proliferation and differentiation, and (2) the role of different basement membrane associated proteins on the plating efficiency of either isolated or outgrowth epithelial esophageal cells.

Actins↗

PubMed1990

Development of a human stomach explant organ culture system to study the pathogenesis of Helicobacter pylori.

These studies were undertaken to define conditions under which Helicobacter (formerly Campylobacter) pylori and viable human gastric mucosa could coexist in tissue culture with the ultimate goal of developing an in vitro experimental model which could be used to study interactions between H. pylori and gastric epithelium. Antral gastric biopsies obtained at upper endoscopy were placed in culture in either CMRL-1066 or keratinocyte growth media and incubated at 37 degrees C in either an oxygen-enriched environment (45% O2, 50% N2, 5% CO2) or a standard oxygen environment (95% air, 5% CO2). Without selective antibiotics to suppress growth of non-H.-pylori organisms, H. pylori could not be isolated from most initially positive tissue even after only 2 h in tissue culture; however, when selective antibiotics were utilized in the tissue culture media, H. pylori was isolated from 9 of 14 initially positive cases after 24-72 h in tissue culture. There was little difference in the morphology of either surface or glandular epithelium in H.-pylori-negative explants between time zero and 48-hour cultures. However, H.-pylori-positive explants after 48 h in tissue culture showed a significant increase in injury to both surface and glandular epithelium when compared to time zero specimens. These data demonstrate that viable H. pylori and human gastric epithelium can be maintained in explant organ culture and suggest that this gastric mucosal explant culture system may be useful in studying the significance of H. pylori infection of human gastric epithelia.

Culture Media↗

PubMed1989

Hemorrheological investigation on healthy natives and immigrants at 3658 M above sea level in Lhasa.

A hemorrheologic investigation on 186 healthy native and immigrants at an altitude of 3,658 M above sea level revealed that hemorrheologic indexes are statistically higher in males than in females irrespective of natives or immigrants, except that hemoglobin in male immigrants is higher than in male natives. For females, all indexes in immigrants are higher than in natives. In addition, the difference between males and females may be related to the function of androgen in polycythemia due to oxygen shortage.

Adolescent↗

PubMed1988