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Biomedical subjects

Z He

Publications and source records attributed to Z He.

At least 19 recordsLinked to original sources
PubMed2000

Definition of the anterior choroidal artery territory in rats using intraluminal occluding technique.

This manuscript delineates the territory of the anterior choroidal artery (AChA) in rats, as defined by the induction of an AChA infarction. By advancing a 0.24-mm surgical suture up the internal carotid artery (ICA) to a point 0.5-2 mm proximal to the middle cerebral artery (MCA) origin, the AChA could be occluded and a reliable AChA distribution infarction was produced in 62% (23/37) of animals. The infarct volume, as defined by TTC staining, was 55+/-7 mm(3). Maps of the infarction, generated by measuring the entire area of overlapping coronal slices, demonstrated that the internal capsule was always damaged. Other areas that might be affected included the hippocampus, thalamus, amygdaloid complex, piriform cortex, dorsal caudatoputamen, and lateral ventricular wall. Positioning the coated suture proximal to the AChA produced a much smaller infarct involving the medial and lateral hypothalamus, preoptic region, optic chiasm, and marginal region of the internal capsule near to the lateral hypothalamus exempt from AChA territory damage. A causative relationship between AChA occlusion and a deep cerebral infarct centered on the internal capsule was further established by: (1) identifying the AChA on the non-ischemic side with colored silicone perfusion, and subsequent similar delineation on the ischemic side, and (2) delineating infarction in the silicone perfused AChA region using hematoxylin and eosin staining and the TUNEL method. The AChA usually originated from the ICA (91% of cases), 1.75+/-0.12 mm proximal to the MCA bifurcation. Approximately 27% of the AChAs had periamygdaloid branch(es) on its initial segment.

Animals↗
PubMed2000

Cloning and heterologous expression of a sulfur oxygenase/reductase gene from the thermoacidophilic archaeon Acidianus sp. S5 in Escherichia coli.

A thermoacidophilic, obligately chemolithotrophic, facultatively aerobic archaebacterium, Acidianus sp. S5, was isolated from acidothermal springs in southwest China. The sulfur oxygenase/reductase (SOR) gene of Acidianus sp. S5 was cloned and expressed in Escherichia coli. Several primers were designed and successfully applied for detection and cloning of the sor gene. A 3.7-kb EcoRI fragment containing the sor gene and three neighboring open reading frames was sequenced. Sequence analysis indicated that the sor gene of Acidianus sp. S5 showed 81% identity to the sor gene of Acidianus ambivalens. E. coli cells carrying the sor gene on pBV220SOR were able to overproduce SOR upon a temperature shift from 30 to 42 degrees C. SOR produced in E. coli catalyzes the oxidation of elemental sulfur and concomitant production of sulfite, thiosulfate and hydrogen sulfide. The recombinant enzyme exhibits the same catalytic properties as the one from Acidianus S5.

Amino Acid Sequence↗
PubMed2000

The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner.

Semaphorin molecules serve as axon guidance signals that regulate the navigation of neuronal growth cones. Semaphorins have also been implicated in other biological processes, including the immune response. Plexins, acting either alone or in complex with neuropilins, have recently been identified as functional semaphorin receptors. However, the mechanisms of signal transduction by plexins remain largely unknown. We have demonstrated a direct interaction between plexin-B1 and activated Rac. Rac specifically interacts with the cytosolic domain of plexin-B1, but not with that of plexin-A3 or -C1. Neither RhoA nor Cdc42 interacts with plexin-B1, indicating that the Rac/plexin-B1 interaction is highly specific. The binding of GTP and the integrity of the Rac effector domain are required for the interaction with plexin-B1. Furthermore, we have identified that a Cdc42/Rac interactive binding (CRIB) motif in the cytosolic domain of plexin-B1 is essential for its interaction with active Rac. We have also observed that the semaphorin CD100, a ligand for plexin-B1, stimulates the interaction between plexin-B1 and active Rac. Our results support a model by which activated Rac plays a role in mediating semaphorin signals, resulting in reorganization of actin cytoskeletal structure.

Amino Acid Motifs↗
PubMed2000

PCD1, a novel gene containing PDZ and LIM domains, is overexpressed in several human cancers.

In an effort to discover novel genes differentially expressed in human pancreatic cancer, we have identified a gene named PCD1 (pancreatic cancer derived) that is up-regulated in pancreatic dysplasia and cancer relative to normal pancreatic ductal epithelium. We cloned the full length (4572 bp) of this gene, which encodes a novel protein of 1064 amino acids containing a PDZ domain and a LIM domain. An alternatively spliced form with a deletion of 30 bp in the coding region was also found. In situ hybridization results showed that PCD1 is highly expressed in a significant percentage of colon, breast, liver, lung, pancreas, stomach, and prostate tumor tissues but is expressed in very few normal tissues. Northern blot hybridization confirmed the overexpression of PCD1 in colon and breast tumor tissues and also showed strong expression of PCD1 in the heart as well as in HeLa cells. Real-time quantitative reverse transcription-PCR verified the overexpression of PCD1 in primary colon tumors or in liver metastases relative to normal colon tissues in five of eight patients. The PCD1 gene maps to human chromosome 13q21.33. Because of its high levels of expression in neoplastic tissues and the presence of both PDZ and LIM domains, we suggest that PCD1 may play an important role in cytoskeletal reorganization during carcinogenesis.

Amino Acid Sequence↗
PubMed2000

Spatio-temporal interaction with disease mapping.

Markov chain Monte Carlo methods are used to estimate mortality rates under a Bayesian hierarchical model. Spatial correlations are introduced to examine spatial effects relative to both regional and regional changes over time by groups. A special feature of the models is the inclusion of longitudinal variables which will describe temporal trends in mortality or incidences for different population groups. Disease maps are used to illustrate the role of different parameters in the model and pinpointing areas of interesting patterns. The methods are demonstrated by male cancer mortality data from the state of Missouri during 1973-1992. Of special interest will be the geographic variations in the trend of lung cancer mortality over the recent past. Marginal posterior distributions are used to examine effects due to spatial correlations and age difference in temporal trends. Numerical results from the Missouri data show that although spatial correlations exist, they do not have a large effect on the estimated mortality rates.

Aged↗
PubMed2000

Perception of brassinosteroids by the extracellular domain of the receptor kinase BRI1.

An assay was developed to study plant receptor kinase activation and signaling mechanisms. The extracellular leucine-rich repeat (LRR) and transmembrane domains of the Arabidopsis receptor kinase BRI1, which is implicated in brassinosteroid signaling, were fused to the serine/threonine kinase domain of XA21, the rice disease resistance receptor. The chimeric receptor initiates plant defense responses in rice cells upon treatment with brassinosteroids. These results, which indicate that the extracellular domain of BRI1 perceives brassinosteroids, suggest a general signaling mechanism for the LRR receptor kinases of plants. This system should allow the discovery of ligands for the LRR kinases, the largest group of plant receptor kinases.

Arabidopsis↗
PubMed2000

Viral recombinant vaccines to the E6 and E7 antigens of HPV-16.

Most cancerous lesions of the uterine cervix are linked to persistent infections with human papillomaviruses (HPV), most notably HPV-16 or -18. Vaccine-induced immune responses to the HPV early antigens E6 and E7, which contribute to cell transformation and are thus expressed in these cervical cancers, could potentially eradicate malignant cells. We generated recombinant vaccines based on E1-deleted adenovirus human strain 5 or on vaccinia virus strain Copenhagen expressing either the E6 or E7 oncoproteins of HPV-16. The different vaccines were compared in two experimental mouse tumor models employing Balb/c or C57Bl/6 mice. Data presented here demonstrate that depending on the model either CD4(+) or CD8(+) T cells provide protection to tumor cell challenge, resulting in striking differences in the efficacy of the four vaccines under investigation.

Adenoviruses, Human↗
PubMed2000

LMP1 of Epstein-Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression.

Epstein-Barr virus is associated with a number of human proliferative and malignant diseases. It is capable of immortalizing human primary B-lymphocytes in vitro. Studies indicate that latent membrane protein LMP1 is one of the viral proteins essential for this process. In this report, LMP1 was shown to prevent primary mouse embryonic fibroblasts from entering into replicative senescence in vitro. It further suppresses the senescence-associated induction of p16INK4a, commonly believed to be a key regulator of replicative senescence. In addition, LMP1 was shown to prevent premature senescence provoked by oncogenic ras in mouse embryonic fibroblasts, and to inhibit the oncogene ras-mediated induction of p16INK4a and p21WAF1. In parallel, LMP1 also prevents ras-induced premature senescence in rat embryonic fibroblasts REF52 and human diploid fibroblasts IMR90. Moreover, LMP1 is capable of suppressing the p16INK4a promoter in REF52 and Saos-2 cells in a promoter reporter assay. Our findings suggest that with the expression of p16INK4a and replicative senescence being suppressed, LMP1 may play a key role in Epstein-Barr virus-associated proliferative diseases, and it may further contribute to cancer development by preventing premature senescence induced by mitogenic oncogenes.

Animals↗
PubMed2000

Characterization of the functionally related sites in the neural inducing gene noggin.

Previously we have shown that blocking bone morphogenetic protein (BMP) receptor signaling by a dominant negative BMP receptor causes neurogenesis in Xenopus animal caps (ACs), whereas the physiological neural inducer noggin acts as a homodimer physically binding to BMP-4 and disrupting its signaling at the ligand level. The present study attempted to elucidate the relationship between the structure and function of noggin. By replacing some cysteine residues with serine residues through a site-directed mutagenesis strategy, we generated three noggin mutants, C145S, C205S, and C(218, 220, 222)S (3CS). Although mRNAs encoded by these mutants were translated as efficiently as wild-type (WT) noggin mRNA, they behaved differently when expressed in vivo. Expression of WT noggin or C205S in Xenopus ACs converted the explants (prospective ectoderm) into neural tissue, indicated by the neural-like morphology and expression of the pan neural marker NCAM in the ACs. In contrast, ACs expressing C145S or 3CS sustained an epidermal fate like the control caps. Similar results were observed in the mesoderm where C205S (but not C145S and 3CS) displayed dorsalizing activity as well as WT noggin. Altogether, our results suggest that Cys145 alone or Cys(218, 220, 222) as a whole in noggin protein is required for the biological activities of noggin, probably participating in the dimerization of noggin with BMP-4 or itself.

Animals↗
PubMed2000

Nuclear factor-kappaB activation is involved in LMP1-mediated transformation and tumorigenesis of rat-1 fibroblasts.

The mechanism of latent membrane protein LMP1 of EBV in inducing cell transformation and tumorigenesis was investigated in Rat-1 fibroblasts. A plasmid encoding a site-specific mutant of LMP1 defective in binding to tumor necrosis factor receptor-associated death domain protein was constructed. This LMP1(TRADD) gene is 75% defective in nuclear factor (NF)-kappaB activation and 100% defective in activator protein-1 activation. When introduced into Rat-1 cells through retrovirus, the Rat-1-LMP1(TRADD) cells showed a significant reduction of focus formation and decreased tumor growth in nude mice as compared with Rat-1-LMP1 cells, suggesting that NF-kappaB or activator protein-1 activation may be important for LMP1-induced cell transformation. To further delineate the determinants of LMP1-mediated cellular transformation, a retrovirus with a dominant-negative I kappaB alpha was introduced into the transformed Rat-1-LMP1 cells. The presence of I kappaB alpha significantly suppressed both focus formation and tumorigenicity of Rat-1-LMP1 cells. Our results suggest that the activation of NF-kappaB may play an important role in LMP1-mediated cell transformation and tumorigenesis.

Animals↗
PubMed2000

Identification of differentially expressed genes in nasopharyngeal carcinoma by means of the Atlas human cancer cDNA expression array.

PURPOSE: To investigate genes of critical areas, including cell cycle/growth control, apoptosis, oncogene/tumor suppressors and growth factor/cytokines, that are differentially expressed in nasopharyngeal carcinoma. METHODS: The Human Cancer cDNA Atlas, which contains 588 genes relating to tumor biology, was used to screen normal nasopharyngeal tissue, nasopharyngeal cancer (NPC). The reverse transcription/polymerase chain reaction was used to confirm the expression pattern of some genes identified by Atlas hybridization. RESULTS: The differentially expressed cell cycle/growth control regulators in NPC showed a stronger tendency toward cell proliferation with the up-regulation of cyclin D1, cyclin D2 etc. The expression pattern of apoptosis-related genes demonstrated the up-regulation of both anti-apoptotic factors such as the BCL-2-related protein A1, TRAF3, the inhibitor of apoptosis protein A1 (IAPI) and apoptotic pathway elements such as Fas/Apo-1, Apo-2 ligand etc. Among oncogenes/tumor suppressors, MDM2, STAT1 and STAT2 were found to be up-regulated in NPC. The expression profile of growth factors/cytokines showed the up-regulation of many growth-enhancing factors such as EGR1, tumor-derived growth factor 1, platelet-derived growth factor A chain etc. as well as Th1-type cytokines e.g. interleukin-1beta and interferons. A smaller number of genes were down-regulated in nasopharyngeal cancer, such as those encoding ERK1, Raf, secreted apoptosis-related protein 1, CD27BP, transforming growth factor beta2, pre-B-cell-stimulating factor homologue etc. CONCLUSION: The consistent tendency toward cell proliferation, the possibility of a stronger antiapoptotic force that operates on the normal apoptotic pathway, or the autocrine or paracrine growth factors may account for the development of NPC. Some genes are reported for the first time to have changed expression in nasopharyngeal carcinoma. The simple, quick, and high-throughput method of profiling gene expression by cDNA array hybridization provides us with a quick overview of key factors that may be involved in NPC, and may identify genes suitable for further study of carcinogenesis mechanism or targets for possible molecular diagnosis or therapy.

Apoptosis↗
PubMed2000

Microbial Biomass and Community Structure in a Sequence of Soils with Increasing Fertility and Changing Land Use.

The microbial biomass and community structure of eight Chinese red soils with different fertility and land use history was investigated. Two community based microbiological measurements, namely, community level physiological profiling (CLPP) using Biolog sole C source utilization tests and phospholipid fatty acid (PLFA) profiles, were used to investigate the microbial ecology of these soils and to determine how land use alters microbial community structure. Microbial biomass-C and total PLFAs were closely correlated to organic carbon and total nitrogen, indicating that these soil microbial measures are potentially good indices of soil fertility in these highly weathered soils. Metabolic quotients and C source utilization were not correlated with organic carbon or microbial biomass. Multivariate analysis of sole carbon source utilization patterns and PLFAs demonstrated that land use history and plant cover type had a significant impact on microbial community structure. PLFAs showed these differences more than CLPP methods. Consequently, PLFA analysis was a better method for assessing broad-spectrum community differences and at the same time attempting to correlate changes with soil fertility. Soils from tea orchards were particularly distinctive in their CLPP. A modified CLPP method, using absorbance readings at 405 nm and different culture media at pH values of 4.7 and 7.0, showed that the discrimination obtained can be influenced by the culture conditions. This method was used to show that the distinctive microbial community structure in tea orchard soils was not, however, due to differences in pH alone.

Journal Article↗
PubMed2000

Trends during 25 years of coronary artery bypass operation at St. Luke's Medical Center in Milwaukee, Wisconsin.

BACKGROUND: Most studies of changes in coronary artery bypass graft (CABG) operations are from major academic institutions. The present study evaluated changes in CABG operations since 1968 in a community hospital. METHODS: The data were from the St. Luke's Medical Center Cardiovascular Data Registry in Milwaukee, Wisconsin. Mortality rates, risk factors, overall patient risk, and surgical procedures were compared from 1968 to 1994. RESULTS: There was a dramatic decrease in 30-day mortality rates from 1968 to 1972. After 1976, mortality rates increased because of higher risk patients, but the mortality rate, adjusted for patient risk, continued to decline. Both internal mammary arteries and sequential grafts were widely used by 1972, followed by a decline in use until 1980, and then a steep increase in use from 1980 to the present. CONCLUSIONS: This study provided evidence from a community hospital that the skills of the surgical teams improved first dramatically then gradually. The pattern of adapting new surgical techniques suggested that these techniques were critically evaluated for several years after they were introduced.

Aged↗
PubMed2000

Membrane-bound macrophage colony-stimulating factor and its receptor play adhesion molecule-like roles in leukemic cells.

Membrane-bound macrophage colony-stimulating factor (m-M-CSF) is the membrane form M-CSF by alternative splicing. J6-1 leukemic cell line spontaneously forms cell clusters, whose growth depends on the auto-juxtacrine mediated by m-M-CSF and its receptor (M-CSFR). In this study, M-CSFR isolated from J6-1 cells and recombinant human M-CSF soluble receptor (rh-M-CSFsR) were used to study their effects on J6-1 cells. Both receptors inhibited cell proliferation. Use of M-CSFR monoclonal antibodies, M-CSFR or rh-M-CSFsR to block either M-CSFR or m-M-CSF on cell surface inhibited the cluster forming process, while both receptors stimulated cells adhering to culture plate. Furthermore, M-CSFR and/or rh-M-CSFsR caused multiple cellular changes including cytoplasmic pH, multinuclear cell ratio, antigen expression and cell diameter. A [Ca(2+)] rise was induced within 90 s by both receptors. Western blot experiments showed that rh-M-CSFsR caused tyrosine phosphorylation on multiple cytoplasmic proteins of 45 kDa and 55-90 kDa, which could be blocked by H7. These observations suggested that m-M-CSF and M-CSFR mediate J6-1 cell intercellular adhesion with bi-directional signal transduction, and Ca(2+), protein tyrosine kinases, PKC and/or other H7 sensitive kinase(s) involve in the counter-directional signal transduction.

Cell Adhesion↗
PubMed2000

Transformation of rice with the Arabidopsis floral regulator LEAFY causes early heading.

Onset of flowering, or heading date, is an important agronomic trait of cereal crops such as rice and early-heading varieties are required for certain regions in which rice is cultivated. Since the floral control gene LEAFY from Arabidopsis can dramatically accelerate flowering in dictoyledonous plants, the usefulness of LEAFY for manipulating heading date in rice has been tested. Constitutive expression of LEAFY from the cauliflower mosaic virus 35S promoter caused early flowering in transgenic rice, with a heading date that was 26-34 days earlier than that of wild-type plants. Early flowering was accompanied by a small yield penalty and some panicle abnormality. These observations suggest that floral regulatory genes from Arabidopsis are useful tools for heading date improvement in cereal crops.

Arabidopsis↗
PubMed2000

Functional effects of replacing human alpha- and beta-globins with their embryonic globin homologues in defined haemoglobin heterotetramers.

Embryonic- and adult-stage globin subunits assemble into haemoglobin (Hb) heterotetramers that are expressed at low levels throughout human intrauterine development. These haemoglobins differ from adult Hb A (alpha2beta2) by the substitution of embryonic zeta for adult alpha globin (Hb zeta2beta2), or embryonic epsilon for adult beta globin (Hb alpha2epsilon2). Several key physiological properties of these 'semiembryonic' haemoglobins remain undefined, as ethical and methodological considerations have limited their availability from both human sources and conventional expression systems. The current study attempts to estimate how the physiological properties of semiembryonic and adult haemoglobins may differ, by determining whether the O2-binding characteristics of hybrid human/mouse haemoglobins change when human alpha- or beta-globin subunits are replaced by human embryonic zeta- or epsilon-globin subunits respectively. Each of the four human globins is expressed in transgenic mice that are nullizygous for either the endogenous mouse alpha- or beta-globin genes, resulting in the high-level expression of haemoglobins that can be studied either in situ in intact erythrocytes or in vitro. We showed that the exchange of human zeta-globin for human alpha-globin chains increased haemoglobin O2 affinity, both in the presence and in the absence of 2, 3-bisphosphoglycerate (2,3-BPG), and reduced the pH-dependent shift in its oxygen equilibrium curve (Bohr effect). By comparison, hybrid haemoglobins containing either human epsilon-globin or human beta-globin exhibited nearly identical O2-binding properties, both in situ and in vitro, regardless of 2,3-BPG levels or ambient pH. Neither the zeta-for-alpha nor the epsilon-for-beta substitutions substantially altered binding affinity for 2,3-BPG or cooperativity between globin subunits. These studies suggest that semiembryonic haemoglobins that assemble entirely from human subunits may exhibit properties that are similar to those of human Hb A.

Adult↗