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Biomedical subjects

L Bao

Publications and source records attributed to L Bao.

At least 55 records · Page 3Linked to original sources
PubMed1996

A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental analysis of its effect on primary tumor growth.

The family of tissue inhibitors of metalloproteinases (TIMPs) presently numbers four distinct gene products that are specific inhibitors of the matrix metalloproteinases (MMPs). The local balance between MMPs and TIMPs is believed to play a major role in extracellular matrix (ECM) remodeling during development and in diseases such as cancer and arthritis. Unlike the other TIMPs, which are soluble. TIMP-3 is unique in being a component of ECM. Mutations in the human TIMP-3 gene cause a dominantly inherited, adult-onset blindness (Sorsby's fundus dystrophy or SFD). In this article, we summarize what is currently known about TIMP-3, discuss possible mechanisms leading up to SFD, and investigate the effect of TIMP-3 on tumor growth. Breast carcinoma and malignant melanoma cell lines were transfected with TIMP-3 expression plasmids and injected subcutaneously into nude mice. Growth curves of the resulting tumors over a period of 6 to 8 weeks demonstrated that increased expression of TIMP-3 resulted in a statistically significant suppression of tumor growth. Deposition of TIMP-3 in the surrounding ECM by tumor cells may inhibit tumor growth by preventing local expansion of tumor, retarding the release of growth factors sequestered in ECM, or inhibiting angiogenesis. TIMP-3 over-expression had no effect on the growth of the two tumor cell lines in vitro. Because recombinant TIMP-3 inhibits endothelial cell migration and tube formation in response to angiogenic factors, we believe that the effect of TIMP-3 on tumor growth seen in this study may be a consequence of its angiostatic action.

Animals↗
PubMed1996

[Preliminary research of Astangahrdayasamhita].

Astangahrdayasamhita, transmitted into the region of Tibet and Mongolia as Buddist Scripture, is a classical work of ancient Indian medicine. It has had an important influence on the formation of the theoretical system of Tibetan medicine and Mongolian medicine. Divided into six parts, eight branches and 120 chapters, Astangahrdayasamhita describes systematically physiology, pathology, diagnosis and treatment of diseases. This article describes Astangahrdayasamhita in four aspects, including the author and dating of its writing: the main contents; its position in Ayur-vedic medicine; the influence on Tibetan and Mongolian medicine.

China↗
PubMed1996

[16S rRNA gene PCR-SSCP analysis of the reference strains from 15 serovars (14 serogroups) of pathogenic leptospires in China].

The DNAs of reference strains from 15 serovars (14 serogroups) of pathogenic leptospires in China were amplified with 16S rRNA gene primers, and then single-strand conformation polymorphism (SSCP) of the products were analyzed in 12.5% nondenaturing mini polyacrylamide gel (containing 5% glycerol) combining with silver-staining. All products showed two bands on electrophoresis at different parameters of voltage or current and concentration of gel. It proved that serovar lai, serovar canicola, serovar pyrogenes, serovar autumnalis, serovar australis, serovar pomona, serovar linhai, serovar hebdomadis, serovar haemolytica, serovar wolffi and serovar paidjan have the identical pattern (Leptospira interrogans), while serovar javanica, serovar ballum, serovar tarassovi and serovar manhao I belong to another pattern (L. borgpetersenii). The result was consistent with the classification of genetic species by Yasuda et al (1987) and Ramadass et al (1992).

China↗
PubMed1996

[An experimental study on corneal nerve regeneration after penetrating keratoplasty with long-term cryopreserved rabbit corneas].

OBJECTIVE: To observe the morphology of rabbit corneal nerve regeneration in the grafts after penetrating keratoplasty (PKP) with long-term cryopreserved homogeneous donor material. METHODS: Both long-term cryopreserved and short-term moist-chamber preserved fresh rabbit corneas were applied in the keratoplasty. By means of glyoxylic-acid induced fluorescence (GIF) and acetylcholine esterase (AChE) staining histochemical techniques, the morphological features of adrenergic and cholinergic nerve regeneration were monitored under light microscope in those grafts from ten days to eight months after surgery. RESULTS: During various intervals, the morphological changes of neural reinnervation were similar in the two groups, and numerous subepithelial nerves that showed random changes in direction and caliber were apparent. The nerve endings in the epithelium were few. CONCLUSIONS: The cryopreservative procedures do not affect neural regeneration under light microscope. The depressed tactile sensitivity following the surgery is correlated with nerve endings in the epithelium subnormal in number and with the regeneration of corneal nerves abnormal in distribution and morphology.

Adrenergic Fibers↗
PubMed1996

[Detection of Epstein-Barr virus DNA in renal tissue from patients with interstitial nephritis].

In order to demonstrate whether Epstein-Barr virus (EBV) infection might play a role in the pathogenesis of interstitial nephritis as suggested by many scholars, EBV DNA was detected in twelve specimens of frozen renal biopsy tissue from patients with interstitial nephritis by using nest polymerase chain reaction (nest PCR). For comparison, frozen renal biopsy tissue from ten patients with minimal change disease was used as control. Southern blot hybridization was used to check the specificity of PCR product. The results showed that eight of twelve frozen renal biopsy specimens from interstitial nephritis patients were EBV DNA positive (66.7%), as compared with negative in all the ten frozen renal specimens from minimal change disease patients. The differences was statistically significant (P < 0.01). The study strongly suggests that EBV infection may play an important role in the pathogenesis of interstitial nephritis. The location of EBV in renal tissue and the mechanism inducing interstitial nephritis by EBV are to be clarified.

Adult↗
PubMed1995

Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells.

Relatively little is known about the mechanisms used by somatic cells to regulate the replication of the centrosome complex. Centrosome doubling was studied in CHO cells by electron microscopy and immunofluorescence microscopy using human autoimmune anticentrosome antiserum, and by Northern blotting using the cDNA encoding portion of the centrosome autoantigen pericentriolar material (PCM)-1. Centrosome doubling could be dissociated from cycles of DNA synthesis and mitotic division by arresting cells at the G1/S boundary of the cell cycle using either hydroxyurea or aphidicolin. Immunofluorescence micros-copy using SPJ human autoimmune anticentrosome antiserum demonstrated that arrested cells were able to undergo numerous rounds of centrosome replication in the absence of cycles of DNA synthesis and mitosis. Northern blot analysis demonstrated that the synthesis and degradation of the mRNA encoding PCM-1 occurred in a cell cycle-dependent fashion in CHO cells with peak levels of PCM-1 mRNA being present in G1 and S phase cells before mRNA amounts dropped to undetectable levels in G2 and M phases. Conversely, cells arrested at the G1/S boundary of the cell cycle maintained PCM-1 mRNA at artificially elevated levels, providing a possible molecular mechanism for explaining the multiple rounds of centrosome replication that occurred in CHO cells during prolonged hydroxyurea-induced arrest. The capacity to replicate centrosomes could be abolished in hydroxyurea-arrested CHO cells by culturing the cells in dialyzed serum. However, the ability to replicate centrosomes and to synthesize PCM-1 mRNA could be re-initiated by adding EGF to the dialyzed serum. This experimental system should be useful for investigating the positive and negative molecular mechanisms used by somatic cells to regulate the replication of centrosomes and for studying and the methods used by somatic cells for coordinating centrosome duplication with other cell cycle progression events.

Animals↗
PubMed1995

Autoepitope mapping of the centrosome autoantigen PCM-1 using scleroderma sera with anticentrosome autoantibodies.

We previously characterized a scleroderma serum (serum 1) containing autoantibodies against centrosome autoantigens that have been named PCM-1, PCM-2 and PCM-3. In this study, we analyzed another scleroderma serum (serum 2) reactive with centrosome autoantigens of identical molecular weights to those recognized by serum 1. To further analyze the autoepitope domains in PCM-1 recognized by the autoantibodies present in scleroderma sera, cDNAs encoding different portions of the PCM-1 autoantigen were expressed in bacteria as fusion proteins. The immunoreactivity of the fusion proteins to the scleroderma sera was assayed by immunoblot analysis. Two regions containing autoepitope domains reactive with both sera were identified in the PCM-1 molecule. One is between amino acids 312-706 of the PCM-1 autoantigen, and the other is localized between amino acids 1,433-1,787, indicating that the immune response is oligoclonal. The results are important to clarify the mechanism of induction of anticentrosome autoantibodies. The potential diagnostic and prognostic significance of the autoantibodies for subgroups of scleroderma is discussed.

Animals↗
PubMed1995

Complementary distribution of receptors for neurotensin and NPY in small neurons in rat lumbar DRGs and regulation of the receptors and peptides after peripheral axotomy.

Neurotensin (NT) has been reported to have antinociceptive effects at the spinal level. In situ hybridization, electrophysiology, immunohistochemistry, and electronmicroscopy were used to investigate the distribution of NT receptors, possible effects of NT on primary sensory neurons, and the effect of nerve injury on the expression of NT receptors and NT. NT receptor (R) mRNA was observed in more than 25% of the small dorsal root ganglion (DRG) neurons, which lacked neuropeptide Y NPY-R mRNA and essentially other neuropeptide mRNAs. Intracellular recording using voltage-clamp mode showed that NT evokes an outward current in NPY-insensitive small neurons, and NPY an outward current in NT-insensitive small neurons. Both peptides lacked effect on several small DRG neurons. In the superficial dorsal horn NT immunoreactive (IR) terminals directly contacted primary afferent terminals without synaptic specializations. This new category (> 25%) of the small DRG neurons expressing NT-R mRNA was complementary to the around 60% of small neurons expressing NPY-R mRNA (and also substance P and calcitonin gene-related peptide mRNAs) and to the rest exhibiting somatostatin mRNA expression. The electrophysiological results support this classification, showing that NT and NPY have inhibitory effects on separate subpopulations of small DRG neurons. After sciatic nerve transection, a marked decrease was observed in (1) the number of NT-R mRNA-positive neurons in DRGs, (2) NT mRNA-positive neurons in the dorsal horn, and (3) NT-IR cell bodies and fibers in laminae I-II. Thus, axotomy causes downregulation of several NT systems at the spinal level, suggesting that the possible effects of NT on primary sensory neurons is attenuated after peripheral axotomy.

Afferent Pathways↗
PubMed1994

Localization of neuropeptide Y Y1 receptors in the rat nervous system with special reference to somatic receptors on small dorsal root ganglion neurons.

Immunohistochemical staining with an antiserum against the neuropeptide Y (NPY)-Y1 receptor (Y1-R) protein was shown in rat small dorsal root ganglion (DRG) neurons, which also were Y1-R mRNA-positive and calcitonin gene-related peptide (CGRP)-positive. The Y1-R-like immunoreactivity was almost exclusively located in the somatic plasmalemma and in the perinuclear region. Intracellular recording showed that the Y1 agonist [Leu31,Pro34]NPY evoked an outward current in small DRG neurons, suggesting a functional somatic Y1-R. No evidence for axonal transport of Y1-R protein was obtained after analysis of the dorsal horn for double staining with CGRP, after dorsal rhizotomy, or after compression of dorsal roots and the sciatic nerve. It is proposed that blood-borne NPY released from sympathetic nerves and adrenal medulla is the endogenous ligand for the Y1 receptors on the small DRG neurons. Y1-R-positive neurons were also seen in the dorsal horn of spinal cord, the hypothalamic arcuate nucleus, pyramidal cells in the cerebral cortex, Purkinje and basket cells in the cerebellar cortex, and in many other brain regions.

Animals↗
PubMed1994

Increased expression of galanin in the rat superior cervical ganglion after pre- and postganglionic nerve lesions.

Using immunohistochemistry the expression of galanin (GAL) and galanin message-associated peptide (GMAP) in the superior cervical ganglion (SCG) was investigated 2, 4, 7, and 14 days after unilateral transection of the cervical sympathetic trunk (decentralization) or after cutting the external and internal carotid nerves (axotomy), as well as 7 days after removal of parotid gland tissue. In control SCGs including the sympathetic trunk and the carotid nerves, very few neurons and fibers were GAL/GMAP-positive. Two and 7 days after decentralization, about 5% of all counted neuron profiles in the ipsilateral SCG were GAL/GMAP immunoreactive. Immunoreactive cell bodies were distributed throughout the SCG, with a greater number in the most caudal portion of the ganglion. Many GAL/GMAP-positive nerve fibers were observed in the whole SCG, with strongly fluorescent bundles of immunoreactive fibers accumulated at the caudal end of the SCG. Several GAL/GMAP-immunoreactive nerve fibers were seen ipsilaterally in the external carotid nerve, whereas only a few positive fibers could be observed in the internal carotid nerve. About 2% of all counted neuron profiles in SCGs ipsilateral to decentralization still contained GAL/GMAP-immunoreactivity 14 days after the operation. The number of GAL/GMAP-positive cell bodies was at least doubled in the contralateral SCGs after decentralization compared to controls. After axotomy, about 50% of all counted neuron profiles were GAL/GMAP-positive in the ipsilateral SCG and distributed throughout the SCG. A strong accumulation of immunoreactive nerve fibers was observed in both the internal and external carotid nerves. The number of GAL/GMAP-positive cell bodies was slightly increased in the contralateral SCGs. After unilateral removal of parotid gland tissue, many GAL/GMAP-positive cell bodies and some fibers were observed in the caudal half of the ipsilateral SCG. The number of immunoreactive nerve fibers was increased also in the external carotid nerve, but not in the internal carotid nerve. In situ hybridization revealed prepro GAL mRNA in about 5% of all SCG neuron profiles in decentralized SCGs, paralleling the increase seen in GAL/GMAP peptide content. There was also a small increase in prepro VIP mRNA-positive cells in the caudal part of the SCG. The present results indicate that both pre- and postganglionic lesions increase the content of GAL/GMAP in the SCG, with a much more pronounced increase after transection of the carotid nerves.

Animals↗
PubMed1994

Effects of inoculation site and Matrigel on growth and metastasis of human breast cancer cells.

The co-injection of extracellular matrix components, such as Matrigel, with human tumour cells into nude mice has been reported to facilitate tumour formation and growth, but it is unknown whether such components exert similar effects on tumour progression and metastasis. Metastatic behaviour is known to be enhanced when tumour cells are implanted orthotopically, and it is inferred that full and efficient expression of this phenotype may involve some interactions with local connective tissue matrix. It was therefore decided to investigate whether manipulation of the mesenchymal environment by co-injection of extracellular matrix components, in the form of Matrigel, with human breast cancer cells into orthotopic or ectopic sites could augment their metastatic performance, as well as their growth at the site of inoculation. Standard aliquots of 10(6) cells of the polyclonal human breast carcinoma cell line MDA-MB-435, and of four clonal cell lines, two metastatic and two non-metastatic derived from it, were injected with and without Matrigel, orthotopically or subcutaneously into nude mice. The latent period of tumour formation at the inoculation site as well as final tumour size and metastatic performance at autopsy, 140 days after inoculation, were then assessed. The prevalence of metastasis of the parent, polyclonal, cell line and of its metastatic clones was increased if the cell inoculum was mixed with Matrigel. Non-metastatic clones were not induced to become metastatic by this treatment, but local tumour growth at the site of inoculation was enhanced in all experimental groups receiving Matrigel. Orthotopic inoculation acted synergistically with Matrigel to maximise both tumour growth and metastatic behaviour. The composition of the local extracellular matrix at the site of tumour growth influenced expression of the metastatic phenotype by cells which are constitutionally capable of this behaviour, but did not induce it in ones which are not. Previous reports that local tumour growth is facilitated by enrichment of the mesenchymal matrix are confirmed. The mechanisms by which such effects are exerted are worthy of study, to ascertain whether they might be subject to clinical manipulation designed to retard tumour growth and dissemination.

Animals↗
PubMed1994

PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution.

We report the identification and primary sequence of PCM-1, a 228-kD centrosomal protein that exhibits a distinct cell cycle-dependent association with the centrosome complex. Immunofluorescence microscopy using antibodies against recombinant PCM-1 demonstrated that PCM-1 is tightly associated with the centrosome complex through G1, S, and a portion of G2. However, late in G2, as cells prepare for mitosis, PCM-1 dissociates from the centrosome and then remains dispersed throughout the cell during mitosis before re-associating with the centrosomes in the G1 phase progeny cells. These results demonstrate that the pericentriolar material is a dynamic substance whose composition can fluctuate during the cell cycle.

Amino Acid Sequence↗
PubMed1994

[Transcript expression of the CPL 5x, BMD-3A, BMD-10 Interrogans leptospira].

Total RNA of Leptospira interrogans SV Lai strain 017 was prepared by the method of Licl-Urea, and was used in dot hybridization with biotin-labelled DNA probes. The probes included BMD-3A, BMD-10, which were the leptospirial protective antigen genes, and CPL 5x, which was the genus specific gene of interrogans Leptospira. All of the three probes have shown various degrees of hybridization signs, proving that they all have transcript expression in leptospira. The transcript expression is the main way of regulating the gene expression in procaryotae, and it is significant in molecular genetics of Leptospira. The results indicate that the antigens encoded by the BMD-3A, BMD-10 may play an important role in immune reaction against leptospiral infection and provide a clue to the development of gene-engineering vaccine. The results also suggest that the antibody against the antigen encoded by CPL 5x is a useful tool in the classification of Leptospira interrogans.

Antigens, Bacterial↗
PubMed1993

Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization of the human C5a receptor gene.

The human C5a anaphylatoxin and formyl peptide receptor genes, as well as two genes with high sequence identity to the formyl peptide receptor, FPRH1 and FPRH2, have been mapped to chromosome 19 (Lu et al., 1992). Further analysis reveals that these genes are present in the 19q13.3 band adjacent to the 13.3-13.4 interface. MRNAs for the C5a and formyl peptide receptors, as well as for FPRH1, are expressed in cAMP differentiated U937 cells and human eosinophils, while all four transcripts are expressed in human lung. This observation opens the possibility for coordinate regulation of these genes. In order to initiate the mapping of fine structure at this locus, genomic clones have been analyzed. All four of the genes have a similar structure, with the receptor protein encoded in a single exon. Detailed characterization of the C5a receptor gene reveals a two exon structure, with the 5' untranslated sequence and initiating methionine located in the first exon. An intron of approximately 9 kb separates exon 1 from the receptor-encoding exon 2. The region of genomic DNA flanking the 5' untranslated sequence possesses promoter activity when transfected into the myeloid-derived rat basophilic leukemia RBL-1 cells, but the same region is inactive when transfected into nonmyeloid cells. Deletional analyses indicate that C5a receptor 5' flanking region contains both cell-specific suppressor and promoter regions.

Animals↗
PubMed1993

Correlation of VLA-4 integrin expression with metastatic potential in various human tumour cell lines.

This investigation has focused on whether a number of molecular species, which have recently been recognised as components of cell attachment receptors utilised in recirculatory leukocyte traffic, are expressed on metastatic tumour cell populations. This has been studied on live cultured metastatic and non-metastatic tumour cell lines as well as on histological sections of frozen tissue from primary tumours and metastases which they formed after inoculation into nude mice. Here we report data we have obtained using immunofluorescence microscopy, fluorescence activated cell analysis, immunocytochemistry and pathological investigation of tumour behaviour in vivo, which converge to indicate that expression of the integrin molecule VLA-4 is positively associated with the execution of the metastatic process. This molecule is known to be a receptor for at least two ligands, namely the inducible endothelial adhesion molecule VCAM-1 and the extracellular matrix component fibronectin, and is thought to be mechanistically important in the attachment and diapodesis of lymphocytes. The present findings, indicating differential expression of this molecule on metastatic cell populations relative to non-metastatic cell populations, support and extend recent reports from other laboratories, of the presence of various leukocyte adhesion receptors on metastatic tumour cells. This accumulating evidence suggests that inappropriate expression of one or more of these surface adhesion molecules in tumour cell lineages may endow the progeny of the affected clones with some of the properties needed for metastatic behaviour. The total information so far assembled by various groups also provides some early clues suggesting that the types of molecules expressed may be related to the histogenetic origin of the tumour and its pattern of metastatic spread.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Structural diversity in the extracellular faces of peptidergic G-protein-coupled receptors. Molecular cloning of the mouse C5a anaphylatoxin receptor.

The mouse C5a receptor gene was isolated using the human C5a receptor cDNA probe recently described (Gerard, N. P., and C. Gerard. 1991. Nature 349:614). By analogy with the human gene, the mouse homolog contains two exons with the 5' untranslated region and initiating methionine codon present in exon 1 and the remainder of the molecule in exon 2. Generation of an expressible cDNA for the mouse C5a receptor was accomplished using the polymerase chain reaction and a sense oligodeoxynucleotide primer which included an initiation codon just 5' to the sequence encoding the N-linked glycosylation site. When transfected into human 293 kidney epithelial cells the cloned cDNA directs expression of a binding site for human C5a anaphylatoxin with a binding constant of 2.5 +/- 0.3 nM; the human C5a receptor expressed under identical conditions has a Kd of 1.7 +/- 0.2 nM. Overall, the deduced amino acid sequences of the receptors are 65% identical given the analogous gene structures. Alignment of the sequences as seven transmembrane segment receptors reveals that the greatest structural diversity (approximately 70%) exists in the putative extracellular domains. In contrast, species differences among other members of this family of seven membrane-spanning receptors is generally only 10 to 20%, even for receptors whose ligands are relatively small and not expected to interact with sites on the extracellular surfaces. A high degree of structural identify is observed for the C5a receptors in the transmembrane segments and in all but one of the loops predicted to exist in the cytoplasm. Inasmuch as critical structures responsible for high affinity binding of the 74 amino acid polypeptide to both C5a receptors involve features conserved between species, these data provide the starting point for mutagenesis studies to determine the nature of the binding and activation sites for the chemotactic receptors. Additionally, these data provide a reagent for immunologic and molecular genetic studies on the role of C5a receptors in inflammatory models.

Amino Acid Sequence↗