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Biomedical subjects

L Gao

Publications and source records attributed to L Gao.

At least 127 records · Page 7Linked to original sources
PubMed1998

Lactate causes changes in gonococci including increased lipopolysaccharide synthesis during short-term incubation in media containing glucose.

Gonococci (strain BS4(agar)), emerging from lag-phase during 1-1.5 h incubation in a medium containing glucose (28 mM) and either 5 microM or 50 microM sodium lactate, show enhanced capacity for their lipopolysaccharide (LPS) to be sialylated by cytidine 5'-monophospho-N-acetyl neuraminic acid. The sialyltransferase content of the lactate-treated gonococci was not greater than that of control organisms and showed no differences in LPS components. However, the total LPS content of the lactate-treated gonococci was 10-20% higher than that of control organisms, so lactate enhancement may be due to more sialyl receptors becoming available due to an overall stimulation of LPS synthesis. The protein and pentose contents of the lactate-treated gonococci were also higher than those of controls, indicating stimulation of protein synthesis and ribosome production. Electron microscopy showed hair-like external appendages on control but not on lactate-treated gonococci. The above growth conditions are unnatural. However, when concentrations of glucose and lactate were adjusted to values akin to those occurring in vivo (glucose 5 mM alone and with either 1 mM or 10 mM lactate), and gonococcal multiplication occurred during the short incubation period (1-1.5 h), lactate again induced greater contents of LPS, protein and pentose. A high content of LPS, which will contribute to pathogenicity, should be a constant feature of gonococci growing in human urogenital tissues, where lactate is ever present with glucose.

Bacterial Proteins↗
PubMed1998

Mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene can confer altered drug sensitivities.

Two herpes simplex virus mutants containing mutated residues within the conserved Exo III motif of the polymerase gene were previously shown to be defective in 3'-5' exonuclease activity and exhibited extremely high mutation frequencies. In this study, we have shown that these mutants also exhibited higher resistance to phosphonoacetic acid and sensitivity to aphidicolin and all nucleoside analogs tested, including acyclovir and gangciclovir, compared to wild-type virus. Marker transfer experiments and sequencing analyses demonstrated that these altered phenotypes were the result of mutations within the Exo III motif. The data indicate that, aside from leading to exonuclease deficiency, mutations in the Exo III motif may also affect interaction of nucleoside triphosphates with the catalytic sites of polymerase activity.

Amino Acid Sequence↗
PubMed1998

A novel response to dioxin. Induction of ecto-ATPase gene expression.

We used differential display to discover a new gene that the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) regulates in mouse hepatoma cells. Its predicted amino acid sequence suggests that the gene encodes an ecto-ATPase that contains multiple glycosylation sites, conserved cysteine residues, and apyrase conserved regions. cDNA expression experiments in mouse hepatoma cells confirm that the new gene encodes an ecto-ATPase. Wild-type mouse hepatoma cells contain both constitutive and TCDD-inducible ecto-ATPase activity. Induction of ecto-ATPase gene expression by TCDD is direct and occurs at the transcriptional level. Studies in mutant hepatoma cells indicate that induction requires both the aromatic hydrocarbon receptor (AhR) and the AhR nuclear translocator (Arnt). Furthermore, induction requires AhR's transactivation domain, but not that of Arnt. Our findings reveal new aspects of dioxin's biological effects and TCDD-dependent gene regulation.

Adenosine Triphosphatases↗
PubMed1998

Isolation and functional analysis of the promoter of the rat CMP-NeuAc:GM3 alpha2,8 sialyltransferase gene 1.

A 2.1-kb 5'-flanking fragment of the rat CMP-NeuAc:GM3 alpha2,8 sialyltransferase (GD3-synthase) gene was cloned by the genomic walking procedure. The promoter activity of the fragment was assessed in F-11 cells by transient transfection and the locations for the basal and maximal promoter activities were defined. Primer extension analysis identified a transcription start site approximately 98 bp upstream of the ATG start codon. DNA sequence analysis of the promoter revealed a number of consensus binding sites for known transcription factors such as SP1, AP1, NFkappaB, C/EBP and TFIID, and a repeat GC-GT sequence motif seen for the formation of Z-type DNA. Both TATA and CCAAT boxes were not found in the promoter. Our results from deletion constructs suggested that both positive and negative cis-acting regulatory regions were present in this TATA-less promoter of the rat GD3-synthase gene.

Animals↗
PubMed1998

Identification of a two EF-hand Ca2+ binding domain in lobster skeletal muscle ryanodine receptor/Ca2+ release channel.

The lobster skeletal muscle Ca2+ release channel, known also as the ryanodine receptor, is composed of four polypeptides of approximately 5000 amino acids each, like its mammalian counterparts. Clones encoding the carboxy-terminal region of the lobster ryanodine receptor were isolated from a lobster skeletal muscle cDNA library. Analysis of the deduced 1513 carboxy-terminal amino acid sequence suggests a cytoplasmic Ca2+ binding domain consisting of two EF-hand Ca2+ binding motifs (amino acid residues 594-656). The Ca2+ binding properties of this domain were assessed by preparing bacterial fusion proteins with sequences from the lobster Ca2+ binding domain and the corresponding sequences of the rabbit cardiac and skeletal muscle ryanodine receptors. The lobster skeletal muscle fusion protein bound 45Ca2+ in Ca2+ overlays, and bound two Ca2+ under equilibrium binding conditions with a Hill dissociation constant (KH) of 0.9 mM and coefficient (nH) of 1.4. Rabbit skeletal and cardiac fusion proteins bound two Ca2+ with KHs of 3.7 and 3.8 mM and nHs of 1.1 and 1.3, respectively. Similar to results previously reported for the mammalian RyRs, the lobster RyR was activated by micromolar Ca2+ and inhibited by millimolar Ca2+, as determined in single-channel and [3H]ryanodine binding measurements. These results suggest that the two EF-hand Ca2+ binding domain of the lobster Ca2+ release channel as well as the corresponding regions of the mammalian channels may play a role in Ca2+ inactivation of sarcoplasmic reticulum Ca2+ release.

Amino Acid Sequence↗
PubMed1998

Characterization and biological significance of immunosuppressive peptide D2702.75-84(E --> V) binding protein. Isolation of heme oxygenase-1.

This is the first report on peptidic inhibitors of heme oxygenase. Such peptides were originally developed from the immunomodulatory peptide 2702.75-84 which corresponds to amino acid residues 75 to 84 of the alpha1-helix of HLA-B2702 (2702.75-84) and has been shown to be immunosuppressive in vitro and in vivo. In vitro, 2702.75-84 inhibited cytotoxic T- and natural killer cell- mediated target cell lysis, and in vivo peptide therapy resulted in prolongation of heart and skin allograft survival in mice. The peptide was also shown to bind to heat shock protein 70. However, D-enantiomers of 2702.75-84 and derivatives thereof, while still being immunosuppressive, did not bind to heat shock protein 70. This study was designed to identify proteins binding to peptide D2702.75-84(E --> V) (rvnlrialry) consisting of D-amino acids. Compared with 2702.75-84 (RENLRIALRY), glutamic acid residue 76 (E) was replaced with valine (V). Affinity chromatography using immobilized D2702.75-84(E --> V) and mouse and human cell extracts, resulted in the isolation of heme oxygenase-1 (HO-1). Peptide D2702.75-84 inhibited HO activity in vitro in a dose dependent manner. Similar to what has been observed with other inhibitors of HO, administration of peptide into mice resulted in an up-regulation of HO-1 mRNA and protein, as well as enzyme activity in liver, spleen and kidney. Other peptides derived from 2702.75-84 with similar immunomodulatory activity displayed similar effects. In contrast, inactive derivatives of 2702.75-84 had no effect on HO activity. Therefore, the immunosuppressive effects of the described immunomodulatory peptides are similar to those of cobalt-protoporphyrin, a known up-regulator of HO-1. Our results suggest that HO-1 modulation may be a novel mechanism of immunomodulation.

Adjuvants, Immunologic↗
PubMed1998

Stress protein-induced immunosuppression: inhibition of cellular immune effector functions following overexpression of haem oxygenase (HSP 32).

This is the first report on suppression of immune effector functions following upregulation of heat shock protein 32 (HSP 32), known as haem oxygenase (HO-1). Here we evaluated the effect of cobalt-protoporphyrin (CoPP)-induced HO-1 expression on cell-mediated immune responses. Administration of CoPP to CBA mice resulted in overexpression of HO-1 in the spleen, liver and kidneys. In vitro measurements of T cell-mediated and NK-cell-mediated cytotoxicity in spleens from CoPP-treated animals demonstrated a severe suppression of their effector functions while administration of Zn-PP or vitamin B12 had no effect. Furthermore, CoPP therapy decreased the lymphoproliferative alloresponse and differentiation of cytotoxic T cells. Inhibition of proliferation appeared to be due to cell growth arrest with an increased number of cells staying in G0/G1 phase. Despite the suppressed proliferative response, IL-2 production in the MLR was not inhibited. In contrast, CoPP decreased the production of IL-10, IFN-gamma and TNF-alpha. In vivo, CoPP prolonged the survival of heterotopic heart allografts in mice. The immunosuppressive effects following CoPP-mediated upregulation of HO-1 were similar to those observed after peptide-mediated upregulation of HO-1. The results indicate that overexpression of HO results in the inhibition of several immune effector functions and thus provides an explanation for stress-induced immunosuppression.

Animals↗
PubMed1998

Abdominal image segmentation using three-dimensional deformable models.

RATIONALE AND OBJECTIVES: The authors develop a three-dimensional (3-D) deformable surface model-based segmentation scheme for abdominal computed tomography (CT) image segmentation. METHODS: A parameterized 3-D surface model was developed to represent the human abdominal organs. An energy function defined on the direction of the image gradient and the surface normal of the deformable model was introduced to measure the match between the model and image data. A conjugate gradient algorithm was adapted to the minimization of the energy function. RESULTS: Test results for synthetic images showed that the incorporation of surface directional information improved the results over those using only the magnitude of the image gradient. The algorithm was tested on 21 CT datasets. Of the 21 cases tested, 11 were evaluated visually by a radiologist and the results were judged to be without noticeable error. The other 10 were evaluated over a distance function. The average distance was less than 1 voxel. CONCLUSIONS: The deformable model-based segmentation scheme produces robust and acceptable outputs on abdominal CT images.

Algorithms↗
PubMed1998

Regions of human immunodeficiency virus type 1 nef required for function in vivo.

In vivo studies in monkeys and humans have indicated that immunodeficiency viruses with Nef deleted are nonpathogenic in immunocompetent hosts, and this has motivated a search for live attenuated vaccine candidates. However, the mechanisms of action of Nef remain elusive. To define the regions of human immunodeficiency virus type 1 (HIV-1) Nef which mediate in vivo pathogenicity, a series of mutated isogenic viruses were inoculated into human thymic implants in SCID-hu mice. Mutation of several regions, including the myristoylation site at the second glycine and a region encompassing amino acids 41 through 49 of Nef, profoundly affected pathogenicity. Surprisingly, mutations of prolines in either of the two distant PXXP SH3 binding domains did not affect pathogenicity, indicating that these regions are not required for Nef activity in developing T-lineage cells. These data suggest that some functions of Nef described in vitro may not be relevant for in vivo pathogenicity.

Animals↗
PubMed1998

gamma-glutamylcysteine synthetase: mRNA stabilization and independent subunit transcription by 4-hydroxy-2-nonenal.

gamma-Glutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo glutathione (GSH) synthesis, is composed of one catalytic (heavy) and one regulatory (light) subunit. Although both subunits are increased at the mRNA level by oxidants, it is not clear whether they are regulated through the same mechanism. 4-Hydroxy-2-nonenal (4HNE), a lipid peroxidation product, may act as a mediator for the induction of gene expression by oxidants. In the present study, 4HNE was used to study the mechanism of induction of the two GCS subunits in rat lung epithelial L2 cells. 4HNE increased both the transcription rates and the stability of mRNA for both GCS subunits, resulting in an increased mRNA content for both subunits. Both GCS subunit proteins and enzymatic activities also increased. Emetine, a protein synthesis inhibitor, blocked the increase in GCS light subunit mRNA but not the increase in GCS heavy subunit mRNA. This suggested that although 4HNE increased transcription and stabilization of both GCS subunit mRNAs, the signaling pathways involved in the induction of the two GCS subunits differed.

Aldehydes↗
PubMed1998

[Influence of intraspinal implantation of pSVP0MCAT genetically modified Schwann cell in regeneration of injured spinal cord].

In order to observe the role of genetically modified Schwann cell (SC) with pSVP0Mcat in the regeneration of injured spinal cord, the cells were implanted into the spinal cord. Ninety SD rats were used to establish a model of hemi-transection of spinal cord at the level of T8, and were divided into three groups, randomly, that is, pSVP0Mcat modified SC implantation (Group A), SC implantation (Group B) and without cell implantation as control (Group C). After three months the presence of axonal regeneration of the injured spinal cord was examined by means of horseradish peroxidase (HRP) retrograde labelling technique and stereography. The results indicated that HRP labelled cells in Group A and B could be found in the superior region of injured spinal cord and the brain stem such as the red nuclei and oculomotor nuclei. The density of ventral hom neurons of the spinal cord and the number of myelinated axons in 100 microns of the white matter was A > B > C group. In brief, the pSVP0Mcat modified SC intraspinal implantation could promote regeneration of the injured spinal cord.

Animals↗
PubMed1998

A randomized controlled clinical trial on piperacillin/tazobactam versus ticarcillin/clavulanic acid for the treatment of bacterial infections.

OBJECTIVE: To compare the efficacy and safety of two beta-lactam-beta-lactamase inhibitor combinations, piperacillin/tazobactam and ticarcillin/clavulanic acid in the treatment of bacterial infections. METHODS: A randomized, open-labeled, controlled study was conducted for the treatment of 124 hospitalized patients with lower respiratory tract infection and urinary tract infections. Sixty-three patients received piperacillin (4 g)/tazobactam (500 mg) every 8 hours by intravenous infusion and 61 patients received ticarcillin (3 g)/clavulanic acid (200 mg) every 8 hours by intravenous infusion. The duration of treatment was 7-14 days in both groups. RESULTS: Sixty-three of 79 cases who received piperacillin/tazobactam and 61 of 84 cases who received ticarcillin/clavulanic acid were assessable for clinical efficacy. The overall efficacy rates were 90.5% for the piperacillin/tazobactam group and 88.5% for the ticarcillin/clavulanic acid group, whereas the bacterial eradication rates were 90.2% and 92.0%, respectively. 78 (77.2%) of 101 strains isolated from patients produced beta-lactamases. The adverse reaction was evaluated in 65 cases of piperacillin/tazobactam group and 62 cases of ticarcillin/clavulanic acid group. The adverse drug reaction rates were 7.69% (5/65) and 8.06% (5/62), respectively. CONCLUSIONS: Piperacillin/tazobactam and ticarcillin/clavulanic acid were effective and safe for the treatment of lower respiratory tract infections and urinary tract infections caused by beta-lactamase-producing strains. The results showed that there was no statistical difference between these two groups (P > 0.05).

Adolescent↗
PubMed1998

[Experimental study on immune privilege in subretinal space].

OBJECTIVE: To evaluate the immune characteristics of subretinal space. METHODS: Retina of DBA/2 mouse with or without Complete Freund's Adjunvate (CFA), or human peripheral blood mononuclear cell (PBMC), or syngenic retina, and DMEM as negative control were transplanted into subretinal spaces of BALB/C mouse. Delayed-type hypersensitivity (DTH) and specific killing of cytotoxic T lymphocyte (CTL) were detected two weeks later and histopathological examination was carried out as well. RESULTS: There were no significant differences in DTH between four experimental groups and control group, but the specific killing of CTL was significantly higher than that of the control group. Retinal transplant was survival. Immune rejection occurred in human PBMC group. CONCLUSION: Limited immune privilege occurs in a certain degree after subretinal space transplantation.

Animals↗
PubMed1998

[The relationship between laminin and laminin receptor expression to metastasis and survival of breast carcinomas].

OBJECTIVE: To investigate the relationship between laminin (LN) and LN receptor (LN-R) expression to breast carcinoma metastasis and survival. METHOD: The LSAB immunohistochemical method was used to study cytoplasm of primary breast cancer tissue from 109 cases and 37 axillary lymph nodes with metastasis. RESULTS: Immunostaining of LN was detected in 32 (29.4%) primary breast carcinoma and in 5 (13.7%) axillary nodes with metastasis. The expression of LN-R was significantly lower in primary breast carcinomas (55.0%) than in the node-positive tissues (83.8%) (P < 0.05). Among the 64 cases followed up none of the 6 patients with LN positive alone died after 3 years. Whereas, the LN-R positive (including LN-R positive alone or both LN and LN-R positive) cases had a significantly poorer prognosis when compared with the LN-R negative cases (P < 0.001). Multivariate analysis of clinical and pathological data by Cox regression method demonstrated that both LN-R expression and lymph node status were independent factors affecting the survival of breast cancer patients, but the former had a higher risk (odds ratio = 4.375) than the latter (OR = 2.810). CONCLUSION: These results suggest that LN-R expression is an important biofactor for predicting the prognosis of breast cancer.

Adult↗
PubMed1998

[Gliosis: follow-up and pathological study of 34 cases].

OBJECTIVE: To discuss the etiology, clinical characteristics, pathology and canceration in gliosis. METHOD: 34 cases of gliosis were analyzed retrospectively follow-up for a long period. Their pathologic slices were restudied. RESULT: The causes of gliosis included cranial infection, specially infection caused by virus without distinct symptoms cerebral ischemia, brain injury, radiological treatment of brain. most cases showed symptoms of intracranial hypertension, 55.9% of the patients accompanied with epilepsy. Pathological examination revealed proliferation of small gliosis in all cases, lligodendrogliosis in 79.4% of the cases. The cases with proliferation had better rehabilitation. Canceration was noted in 11.8% of all cases. CONCLUSION: Gliosis is a nonmalignant disease, however, it has the possibility of canceration.

Adolescent↗