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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 721 records · Page 40Linked to original sources
PubMed1996

Vaginal transmission of chimeric simian/human immunodeficiency viruses in rhesus macaques.

Chimeric simian/human immunodeficiency viruses (SHIVs) that express the env genes derived from distinct HIV type 1 (HIV-1) isolates were tested for the ability to infect rhesus macaques following intravaginal inoculation. SHIVs containing either the HIV-1 HXBc2 or the HIV-1 89.6 envelope glycoproteins were capable of replicating in intravenously inoculated rhesus macaques. However, intravaginal inoculation of animals with these two SHIVs resulted in infection only with the SHIV containing the HIV-1 89.6 glycoprotein. Thus, properties conferred by the envelope glycoproteins in the chimeric virus affect the ability of particular SHIVs to initiate a systemic infection following vaginal inoculation. These results provide indirect support for the hypothesis that the selection of specific viral variants occurs in the genital tracts of individuals exposed to HIV by sexual contact.

Acquired Immunodeficiency Syndrome↗
PubMed1996

An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys.

To explore the roles played by specific human immunodeficiency virus type 1 (HIV-1) genes in determining the in vivo replicative capacity of AIDS viruses, we have examined the replication kinetics and virus-specific immune responses in rhesus monkeys following infection with two chimeric simian/human immunodeficiency viruses (SHIVs). These viruses were composed of simian immunodeficiency virus SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rep. Virus replication was assessed during primary infection of rhesus monkeys by measuring plasma SIVmac p27 levels and by quantifying virus replication in lymph nodes using in situ hybridization. SHIV-HXBc2, which expresses the HIV-1 env of a T-cell-tropic, laboratory-adapted strain of HIV-1 (HXBc2), replicated well in rhesus monkey peripheral blood leukocytes (PBL) in vitro but replicated only to low levels when inoculated in rhesus monkeys. In contrast, SHIV-89.6 was constructed with the HIV-1 env gene of a T-cell- and macrophage-tropic clone of a patient isolate of HIV-1 (89.6). This virus replicated to a lower level in monkey PBL in vitro but replicated to a higher degree in monkeys during primary infection. Moreover, monkeys infected with SHIV-89.6 developed an inversion in the PBL CD4/CD8 ratio coincident with the clearance of primary viremia. The differences in the in vivo consequences of infection by these two SHIVs could not be explained by differences in the immune responses elicited by these viruses, since infected animals had comparable type-specific neutralizing antibody titers, proliferative responses to recombinant HIV-1 gp120, and virus-specific cytolytic effector T-cell responses. With the demonstration that a chimeric SHIV can replicate to high levels during primary infection in rhesus monkeys, this model can now be used to define genetic determinants of HIV-1 pathogenicity.

Animals↗
PubMed1996

Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation.

We have identified a human Rho protein, RhoE, which has unusual structural and biochemical properties that suggest a novel mechanism of regulation. Within a region that is highly conserved among small GTPases, RhoE contains amino acid differences specifically at three positions that confer oncogenicity to Ras (12, 59, and 61). As predicted by these substitutions, which impair GTP hydrolysis in Ras, RhoE binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Replacing all three positions in RhoE with conventional amino acids completely restores GTPase activity. In vivo, RhoE is found exclusively in the GTP-bound form, suggesting that unlike previously characterized small GTPases, RhoE may be normally maintained in an activated state. Thus, amino acid changes in Ras that are selected during tumorigenesis have evolved naturally in this Rho protein and have similar consequences for catalytic function. All previously described Rho family proteins are modified by geranylgeranylation, a lipid attachment required for proper membrane localization. In contrast, the carboxy-terminal sequence of RhoE predicts that, like Ras proteins, RhoE is normally farnesylated. Indeed, we have found that RhoE in farnesylated in vivo and that this modification is required for association with the plasma membrane and with an unidentified cellular structure that may play a role in adhesion. Thus, two unusual structural features of this novel Rho protein suggest a striking evolutionary divergence from the Rho family of GTPases.

Amino Acid Sequence↗
PubMed1996

Dorsal root reflexes in articular afferents occur bilaterally in a chronic model of arthritis in rats.

1. Chronic arthritis was produced in rats by the injection of incomplete Freund's adjuvant into one knee joint. By 3-5 days later the rats had developed unilateral swelling of the injected knee and demonstrated bilateral hyperalgesia to radiant heat stimuli applied to the foot. 2. In the same rats anesthetized 3-5 days after the injection, dorsal root reflexes could be recorded bilaterally from the proximal ends of the cut medial articular nerves (MANs) of the knee joint. 3. The dorsal root reflexes consisted of large, medium-sized, and small action potentials evoked in response to phasic mechanical stimulation of the lateral aspect of the knee. The activity was greater in the MAN ipsilateral to the injection than in the contralateral MAN. 4. Local application of capsaicin on the side ipsilateral or contralateral to the arthritis dramatically reduced the dorsal root reflexes recorded from the contralateral MAN, indicating that these dorsal root reflexes depended on activity in fine afferent fibers containing capsaicin receptors, presumably C fibers. Local application of capsaicin on either side did not significantly change the dorsal root reflexes recorded from the ipsilateral MAN. These dorsal root reflexes were presumably conducted in afferent fibers that lacked capsaicin receptors, including A beta- and A delta-fibers.

Action Potentials↗
PubMed1996

Vitamin D regulation of metalloproteinase activity in matrix vesicles.

Matrix vesicles (MVs) are enriched in matrix metalloproteinases (MMPs) capable of degrading proteoglycans. The aim of the present study was to identify which MMPs are present in MVs and determine whether these MMPs are regulated by 1,25-(OH)2D3 [1,25] and 24,25-(OH)2D3 [24,25]. To do this, growth zone (GC) and resting zone (RC) chondrocytes were isolated from rate costochondral cartilage and placed into culture. At confluence, GCs were treated with 1,25 and RCs with 24,25 for 24 hours. MVs, plasma membranes (PMs), and conditioned media were then collected from the cultures. RTPCR demonstrated the presence of mRNA for stromelysin-1 and 72 kDa gelatinase in both RCs and GCs, Casein zymography revealed activity at M(r) 48 and 28 kDa in MV, but not PM or conditioned media; Western analysis confirmed that this activity was stromelysin-1. Gelatinolytic activity, at low levels, was also found in MVs, but not PMs or conditioned media. When enzyme activity was measured using a proteoglycan bead assay, it was found that both GCs and RCs produced MVs and PMs containing neutral metalloproteinase. Both cells also produced MVs and PMs containing plasminogen activator. The addition of 1,25 to GCs caused a significant 4- to 5-fold increase in metalloproteinase activity in MVs, but not PMs. In contrast, MVs from cultures of RCs treated with 24,25 contained decreased metalloproteinase activity; enzyme activity in PMs was unaffected by 24,25. Plasminogen activator in MVs from RC was increased by treatment with 24,25, while MV enzyme activity was decreased after treatment of GC cultures with 1,25. This study shows that both RCs and GCs produce stromelysin-1 and 72 kDa gelatinase and that these enzymes are preferentially localized in MVs. Further, MMP and plasminogen activator activities in MVs and PMs are regulated by vitamin D metabolites.

24,25-Dihydroxyvitamin D 3↗
PubMed1996

[C-myc activation by translocation in human primary non-small cell lung cancer].

OBJECTIVE: Lung cancer is one of the most common human neoplasms. The carcinogenesis and development of lung cancer are related to activation and inactivation of many oncogenes and tumor-suppressor genes. We reported c-myc activation by translocation in SV40T-transformed human bronchial epithelial cells and lung cancer cell line before. In order to confirm that c-myc translocation exists in human primary non-small cell lung cancer, we continued our studies in 12 primary human lung cancers. METHODS: We applied major fluorescence in situ hybridization (FISH) in combination with immunohistochemistry. RESULTS: c-myc translocation was detected in two cases of the 12 primary lung cancers. Overexpression of c-myc was detected in the two cases by means of immunohistochemistry. CONCLUSION: These results suggest that c-myc can be activated by translocation in human primary lung cancer.

Adenocarcinoma↗
PubMed1996

Inhibitory interactions controlling organizer activity in fish.

An experimental system allowing the observation of 2 active organizing centers during zebrafish development is described. It was achieved by injection into a single marginal cell at the 16-cell stage of TARAM-A-D mRNA. TARAM-A-D was previously described as the mutated constitutive form of a type I receptor for transforming growth factor beta. In 80% of the injected embryos, 2 distinct organizers were observed at the onset of gastrulation. At the end of gastrulation, these embryos showed duplicated axial structures. Nevertheless, only 25% of the injected embryos displayed a recognizable axis duplication after 1 day of development. This paradox is taken as an evidence for suppressive effects exerted in a reciprocal manner when more than 1 organizing center is present.

Animals↗
PubMed1996

[Analysis of DNA methylation pattern of c-myc oncogene in hepatocellular carcinoma].

OBJECTIVES: To assess whether hypomethylation of c-myc gene occours in HCC and to determine its clinical significance. METHODS: The methylation pattern at 3' end of c-myc gene was analyzed by Southern blot using methylation sensitive restrcition endonuclease enzymes Hpa I and Msp I in six normal liver tissues and 18 HCCs. RESULTS: At least 5 CCGG sites were methylated at 3' end of c-myc gene in 6 normal liver tissues. However, the normal hypermethylation pattern was absent in 11 hepatocellular carcinoms (HCC) which showed different degree of hypomethylation even if among subclonal cells of same tumour tissues. The hypomethylation was observed more often in markedly advanced HCC with metastasis and poorly differentiated histological grade. CONCLUSION: Scattered CpG at 3' end of c-myc gene was methylated in normal liver tissues. Methyl groups were deleted in different extent in HCC, which can lead to abnormal expression of c-myc gene. The hypomethylation of c-myc can reflect the malignlant extent of HCC and may serve as a useful prognostic indicator in clinical practice.

Carcinoma, Hepatocellular↗
PubMed1996

[Correlation of multiple gene changes with malignant phenotype of human gastric carcinoma].

OBJECTIVE: To investigate the alteration of oncogenes and tumor suppressor genes in gastric carcinogenesis. METHODS: Southern blot, PCR/SSCP and DNA sequencing techniques were used in 33 gastric carcinomas to detect c-met, EGFR, c-erbB-2, AKT-2, c-Ha-ras, p53, p16 and nm23-H1, for the presence of amplification, deletion, mutation and rearrangement. RESULTS: Most tumors (70%) haboured one or more altered genes. The number and type of gene alteration were different among individuals. Rearrangement of c-met was noted in 2/33 cases (6%), and amplification of c-met, c-erbB-2 and AKT-2 in 8/33 cases (24.2%), 1/33 cases (3%) and 2/18 cases (11%) respectively. Homozygous deletion of P16 was seen in 6/33 cases (18%). Loss of heterozygousity was also noted in nm23-H1 5/17 (29%) and p53 2/13 (16%). The mutation rate of p53 in exon 5-8 was 20/33 (61%). Point mutation of p53 was found at both early and advanced tumors. In contrast, amplification of oncogenes and loss of tumor suppressor genes were correlated with poorly differentiated and metastatic tumors. CONCLUSIONS: Gastric carcinogenesis is a gradually developed process, results from sequencial alteration of multigenes. The malignant phenotype is associated with the degree of genetic abnormality.

Adenocarcinoma↗
PubMed1996

[Deletion and down-regulation of mts1/p16 gene in human gastric cancer].

Deletion of mts1/p16 gene was frequently detected in many human tumor cell lines. However, whether alteration of the p16 gene was involved in human gastric carcinogenesis, it is not clear. In order to determine the incidence and correlation of the p16 gene deletion with human gastric cancer, we performed analyses of PCR, Southern and Northern blotting on 85 fresh tumor specimens and 5 tumor cell lines from gastric cancer patients. Homozygous deletion was observed in 1 cell line and down-regulation of expression was observed in 3. High rate of gene deletion was detected by PCR in 14 of 85 fresh tumor tissues. Gene deletion was confirmed by Southern blot analysis with p16 cDNA probe in 6 out of 26 tumor specimens examined.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1996

Role of transforming growth factor beta (TGF-beta) in repairing of bone defects.

TGF-beta is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-beta, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1.5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-beta that consisted of carrier and bovine TGF-beta. Limbs served as controls received carrier alone. The defects were examined radiographically and histologically at 4, 8, 12, 16 and 20 weeks after implantation. The results showed that in TGF-beta implant group, the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen; while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-beta initiate osteogenesis and stimulate the bone defects repair in animal model.

Animals↗
PubMed1996

[Amplification and expression of c-erbB2 oncogene in normal, hyperplastic, and malignant endometria].

OBJECTIVE: To study the correlation of development and survival with amplification of c-erbB2 oncogene in endometrial carcinoma. METHODS: The amplification and expression of c-erbB2 oncogene were determined from formalin-fixed, paraffin-embedded tissues of 25 normal, 31 hyperplastic, and 72 malignant samples of the endometrium in 128 patients, using differential polymerase chain reaction (DPCR) and an immunohistochemical technique. RESULTS: Amplified c-erbB2 (2 to 12 copies) were found in two of 25 (8.0%) normal, 15 of 31 (48.4%) hyperplastic, and 45 of 72 (62.5%) malignant samples. When the results of DPCR were compared with those of the immunohistochemical method, the negative findings concide well with one another, i.e., nonamplification was associated with the absence of immunoreactivity. It was noted that the amplified c-erbB2 was found more significantly in complex and a typical hyperplasias than in simple hyperplasias. The high-level c-erbB2 amplification (at least five copies) was significantly correlated with the histological grade of endometrial carcinoma and vascular or lymphatic invasion. No correlation was seen between c-erbB2 amplification and overall survival in the present group of patients. CONCLUSIONS: The amplified c-erbB2 may play a potential role in the early development of some endometrial carcinomas. The high-level c-erbB2 amplification may identify a subset of aggressive endometrial carcinoma that involves vascular or lymphatic invasiveness and poor cell differentiation playing the role of a marker for clinical prognosis.

Endometrial Hyperplasia↗
PubMed1996

[Expression of p53 gene in oral squamous cell carcinoma and its relations with clinical and pathological parameters and prognosis of patients].

One hundred and eleven cases of oral squamous cell carcinoma (OSCC) were examined for overexpression of p53 protein by using immunohistochemical technique. Association of p53 protein overexpression with clinical and pathological parameters as well as prognosis of patients were also analyzed, p53 protein overexpression was commonly observed (69.4%) in the OSCC patients and might be used as a marker of carcinogenesis of OSCC. The level of p53 protein overexpression was correlated with the decreased three and/or five-year survival rate of OSCC. The presence of p53 was not correlated with patient's sex and age, site and size of tumor, degree of differentiation, node status or clinical stage of OSCC. Single factor COX proportional hazards regression model analysis indicated that there was no significant relationship between p53 overexpression and prognosis of OSCC. Multivariable COX model analysis failed to establish effective life function or risk rate function. This showed that all the parameters analyzed in this study as well as p53 overexpression were not significant or effective risk factors to predict prognosis of OSCC patients.

Adult↗
PubMed1996

[Cloning and identification of the Mycobacterium bovis BCG gene for signal peptide of antigen 85-B].

OBJECTIVE: To clone and identify the Mycobacterium bovis BCG gene for signal peptide of antigen 85-B. METHODS: Using a polymerase chain reaction technique, the signal peptide sequence (position 94 to 211) of antigen 85-B was technique, which is one of the major protein secreted by Mycobacterium bovis BCG (Bacille-Calmette-Guerin). The gene of 117bp fragment was cloned into the SacI and EcoRI sites of pBluecript SK, and its sequence was determined by using T7DNA polymerase kit. RESULTS: The sequence analysis showed that the sequence of 117bp signal peptide was not misincorporated and in 3' end understream of signal peptide the 12 multi cloning sites for foreign gene could be provided by the recombinant plasmid. CONCLUSIONS: The signal sequence of BCG antigen 85-B was cloned into the pBluescript plasmid. The recombinant plasmid was called BCG-S01. According to the genetic information a secreted protein from M. bovis BCG could be utilized in making a useful vaccine vehicle to produce and secrete a vaccinal protein from M. bovis BCG living cells.

Antigens, Bacterial↗
PubMed1996

[Changes of chemical constituents of radix Sophorae flavescentis in complex formulas of traditional Chinese medicine].

Experiments have been made on the changes of chemical constituents in complex formulas of traditional Chinese medicine. The results show that in the complex formula containing Radix Sophorae Flavescentis, as affected by various conditions of processing such as water, temperature and coexisting reductive substances, the content of oxymatrine tends to decrease gradually to disappear while that of matrine increase gradually.

Alkaloids↗