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Biomedical subjects

Q Zhao

Publications and source records attributed to Q Zhao.

287 records · Page 16Linked to original sources
PubMed1989

Neurotropism to tissue specificity in nerve regeneration. Experimental study on sciatic nerves of rat.

Using the left sciatic nerves of 44 rats we studied neurotropism in nerve regeneration. The proximal and distal cut ends of the nerves were separately introduced into the ends of a specially designed silastic Y- or cross-shaped tube. Either the distal stump or a cut end of the Achilles tendon was inserted into the other ends of the tube, or was left empty. The distance between the tissue ends, nerve-to-nerve or nerve-to-tendon, was 4 mm. Four weeks later, neurofibers sprung out from the proximal stump and grew towards the distal nerve end instead of the tendon end or the vacant channel of the tube. This finding suggests that neurotropic factors may influence the direction of growth of the newly formed neurofibers. This paper discusses the mechanism of neurotropism, the effect of the distance between the cut ends of the nerve, and the choice of the silastic material.

Achilles Tendon↗
PubMed1989

[Phentolamine in cases of liver cirrhosis with bleeding from esophageal variceal rupture].

The aim of this study is at establishing cirrhotic portal hypertension with common bile duct ligation in 9 mongrel dogs to measure the plasma catecholamine level. On the basis of experimental study, phentolamine, the alpha-adrenoceptor antagonist, was used to treat 14 patients with liver cirrhosis complicating bleeding from esophageal variceal rupture. The results had been shown that the levels of noradrenaline (NE) in both portal and inferior caval vein were increased more significantly in the cirrhotic stage than in the precirrhotic stage. The mechanism of the NE elevation might be due to increased release from enhancement of sympathetic nervous activity. Our clinical data have also been demonstrated that the effect of phentolamine on the 12 cases of variceal hemorrhage is markedly efficacious with no longer bleeding. Only 2 patients had showed no good reaction neither to phentolamine nor to pituiterin, eventually died of liver failure. It is conceivable that phentolamine has the same efficacy in treatment of esophageal variceal bleeding as pituitrin. But less side effect than the latter.

Animals↗
PubMed1989

[Neurotropism to tissue specificity in nerve regeneration: an experimental study on the sciatic nerves of the rat].

A study of neurotropism in nerve regeneration was carried out on 44 rats, using their left sciatic nerves severed to work up. The cut ends of proximal and distal stumps were separately introduced into amend of the specially designed silastic tube of Y- or cross-shape. Into the other ends of the tube were inserted either the end of the distal stump or a cut end of achilis tendon on the same side, or were left empty. The distance between the tissue ends, nerve-to-nerve or nerve-to-tendon, was 4 mm. Four weeks later, it was found in the specimens that the growth of neurofibers sprung out from the end of the proximal stump directed towards the distal nerve stump rather than towards the tendon end or the vacant limb of the tube. This fact strongly speaks for that there is some thing neurotropic factor, guiding the direction of growth of the newly formed neurofibers, a property of tissue specificity. The mechanism of neurotropism, the effect of the distance between the cut ends of the nerve and the choice of the silastic material were discussed.

Animals↗
PubMedDate not supplied

Crystallization and preliminary X-ray diffraction studies of human cytochrome P450 reductase.

The two functional domains of a cloned human fibroblast NADPH-cytochrome P450 reductase have been expressed in Escherichia coli and purified on the milligram scale for crystallization studies. One domain contains the cofactor FMN-binding site and the other contains the binding sites for cofactor FAD and substrate NADPH. Crystals of both domains have been obtained by the microbatch method. The crystals of the FMN domain belong to the monoclinic space group P21, with unit cell dimensions of a = 39.3 A, b = 51.5 A, c = 47.8 A, and beta = 105.7 degrees and have one molecule in the asymmetric unit. Diffraction data up to 2.3 A were collected with a merging residual on intensity of 9.3%. The crystals of the FAD/NADPH domain belong to the ortho-rhombic space group P212121 with unit cell dimensions of a = 55.9 A, b = 58.6 A, c = 131.1 A and have one molecule in the asymmetric unit. Diffraction data up to 2.6 A were collected with a merging residual on intensity of 8.0%.

Amino Acid Sequence↗
PubMedDate not supplied

Synthesis, hybridization properties, nuclease stability, and cellular uptake of the oligonucleotide--amino-beta-cyclodextrins and adamantane conjugates.

Synthesis of the oligonucleotides conjugated with amino derivatives of beta-cyclodextrin and adamantane, at the 3'-end of host oligonucleotide, has been described. The oligonucleotide conjugates were examined for their nuclease stability, hybridization properties, and cellular uptake. The oligonucleotide conjugates had increased nuclease resistance compared to their parent oligonucleotides. Conjugation of adamantane to the oligonucleotides did not adversely affect the ability of the oligonucleotides to hybridize with their complementary RNA. Conjugation with amino derivatives of beta-cyclodextrin, however, significantly destabilized the duplex formation. In the cellular uptake studies, we found that amino derivatives of beta-cyclodextrin attached at 3'-end of the oligonucleotides did not help to increase the uptake by cells. Cellular uptake of oligonucleotide-adamantane conjugates in association with 2-(hydroxypropyl)-beta-cyclodextrin (HPCD) as a "carrier" was significantly higher than that of control oligonucleotides.

Adamantane↗
PubMedDate not supplied

Preparation and purification of an end to end coupled mEGF-dextran conjugate.

The amino terminus of mouse epidermal growth factor (mEGF) was coupled directly to the aldehyde end of dextran through a reductive amination procedure. The highest coupling efficiency was approximately 80% and could be reached after approximately 24 h of reaction time at pH 8. Gel filtration on Sephadex G-50 Fine removed free mEGF from the conjugate. Preparative polyacrylamide gel electrophoresis was used to separate the conjugate from excess noncharged dextran. The conjugate bound specifically to the EGF receptor on cultured glioma cells as shown in displacement tests with free mEGF. The conjugate was stable in the pH interval 4-9, in 2 M sodium chloride, in 7 M urea, and in human serum and could still bind to the EGF receptor after such treatments. The conjugates are candidates for targeted nuclide therapy.

Amination↗
PubMedDate not supplied

Effects of dextranation on the pharmacokinetics of short peptides. A PET study on mEGF.

The effects of dextranation on the biodistribution of mouse epidermal growth factor (mEGF, 6 kDa) were assessed. By reductive amination, mEGF was coupled to 13 and 46 kDa dextran. The two dextranated conjugates and free mEGF were labeled with the positron-emitting nuclide (76)Br (T(1/2) = 16 h). After intravenous administration to Sprague Dawley rats, the radioactivity biodistribution was evaluated by positron emission tomography (PET) and by measurements of dissected tissues. The dextranation prolonged the retention time in blood, especially when the dextran chain was long. [(76)Br]mEGF-dextran conjugates were shown to have significantly, more than 5 times, lower kidney accumulation than the nonconjugated [(76)Br]mEGF. In conclusion, dextranation affects the biodistribution of mEGF in vivo giving a prolonged circulation time, a decreased uptake in kidney, and an increased spleen accumulation.

Animals↗
PubMedDate not supplied

A statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophoric molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis.

A statistical sampling protocol is described to assess the fidelity of libraries encoded with molecular tags. The methodology, termed library QA, is based on the combined application of tag decode analysis and single bead LC/MS. The physical existence of library compounds eluted from beads is established by comparing the molecular weight predicted by tag decode with empirical measurement. The goal of sampling is to provide information on overall library fidelity and an indication of the performance of individual library synthons. The minimal sampling size n for library QA is l0 x the largest synthon set. Data are reported as proportion (p) +/- lower and upper boundary (lb-ub) computed at the 95% confidence level (alpha = 0.05). As a practical demonstration, library QA was performed on a 25,200-member library of statine amides (size = 40 x 63 x 10). Sampling was conducted three times at n approximately 630 beads per run for a total of 1902 beads. The overall proportions found for the three runs were consistent with one another: p = 84.4%, lb-ub = 81.5-87.2%; p = 83.1%, lb-ub = 80.2-85.95; and p = 84.5%, lb-ub = 81.8-87.3%, suggesting the true value of p is close to 84% compound confirmation. The performance pi of individual synthons was also computed. Corroboration of QA data with biological screening results obtained from assaying the library against cathepsin D and plasmepsin II is discussed.

Journal Article↗
PubMedDate not supplied

Role of prosaposin in the male reproductive system: effect of prosaposin inactivation on the testis, epididymis, prostate, and seminal vesicles.

SGP-1/prosaposin can be secreted or targeted to the lysosomes where it is processed into smaller saposins (A, B, C, and D) required for the hydrolysis of glycosphingolipids. The deficiency of saposins B and C results in variant forms of metachromatic leukodystrophy and Gaucher's disease, respectively, which are characterized by lysosomal storage of undegraded glycosphingolipids. In the nervous system, prosaposin presents trophic activity. A mouse model was recently developed by creating a null allele in embryonic stem cells through gene targeting to investigate the phenotypic diversity of prosaposin mutations and the involvement of this protein in lysosomal storage diseases, and for the development of therapeutic approaches. Mice homozygous mutants die at the age of 35-40 days and neurological disorders contribute to the early demise of the mutant mice. The male reproductive organs in homozygous mutants show several abnormalities, such as a decrease in testis size with reduced spermiogenesis and an involution of the prostate, seminal vesicles, and epididymis. In these animals, the blood levels of testosterone remain normal. In the prostate of homozygous mutants, only the basal epithelial cells appear to be present, while the secretory cells are absent. These findings suggest that prosaposin may be involved in the development and maintenance of the male reproductive organs, as well as, in cellular differentiation.

Animals↗
PubMedDate not supplied

Immune response against 3LL Lewis lung carcinoma potentiates the therapeutic efficacy of endostatin.

The ability of the antitumor immune response to potentiate the therapeutic efficacy of the antiangiogenic agent endostatin was investigated. The antitumor effects of endostatin were tested against weakly immunogenic 3LL Lewis lung carcinoma and its highly immunogenic variant 3LL-C75. Using in vivo Matrigel assay, it was found that the recombinant endostatin produced in the authors' laboratory has a potent antiangiogenic effect. Endostatin manifested a more potent antitumor effect against highly immunogenic 3LL-C75 than weakly immunogenic 3LL tumor. Endostatin induced regression of immunogenic 3LL-C75 tumor in 40% of C57BL/6 mice, whereas partial inhibition and no regression were found in mice bearing weakly immunogenic 3LL tumor. 3LL and 3LL-C75 cells produced similar amounts of Vascular Endothelial Growth Factor, and immunohistochemical analysis revealed that endostatin treatment reduced microvessel density in both 3LL and 3LL-C75 tumors. However, infiltration of T lymphocytes was observed in 3LL-C75 but not in 3LL tumors. These results suggest that the host's immune response may potentiate the antitumor effects of antiangiogenic agents. This possibility was further supported by findings that the antitumor activity of endostatin against 3LL-C75 tumor was lower in immunodeficient than in immunocompetent mice. Stimulation of immune response against 3LL tumor by vaccination with highly immunogenic 3LL-C75 cells substantially increased the antitumor effect of endostatain, resulting in a complete and permanent regression of 3LL tumor in 50% of mice. Tumor vaccination or endostatin treatment applied separately inhibited but did not induce regression of 3LL tumor. These results suggest that the combined attack against tumor cells and the tumor vascular system using antitumor immune mechanisms and antiangiogenic drugs can be a promising strategy for cancer treatment.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Targeted disruption of the mouse prosaposin gene affects the development of the prostate gland and other male reproductive organs.

The prosaposin gene encodes a 65-70 kilodalton (kd) protein, which is secreted or targeted to lysosomes. In lysosomes, prosaposin is the precursor of 4 activator proteins, designated saposins A, B, C, and D, which promote by acidic hydrolases, the degradation of glycosphingolipids with short oligosaccharide chains. Mutations of the prosaposin gene have been linked to several lysosomal storage disorders. An animal model was recently developed by creating a null allele in embryonic stem cells through gene targeting in order to investigate the phenotypic diversity of prosaposin mutations, the involvement of this protein in lysosomal storage diseases, and to develop potential therapeutic approaches. Mutant homozygous mice die at 35-40 days of age and neurological disorders contribute to their early death. Secreted prosaposin is present in milk and in cerebrospinal and seminal fluids. In the nervous system, prosaposin exhibits a trophic activity. Examination of reproduc-tive organs in homozygous mutant males shows several abnormalities such as a decrease in testis size with reduced spermiogenesis, and an involution of the prostate, seminal vesicle, and epididymis, although levels of testosterone in blood remain normal. In the prostate of homozygous mutants, only basal cells appear to be present, whereas secretory cells are absent. The epithelia in efferent ducts is formed by ciliated cells, whereas heterozygotes exhibit a majority of nonciliated cells. Our data indicate that prosaposin is involved in the development and maintenance of male reproductive organs. In prostatic epithelium, targeted disruption of the prosaposin gene appears to inactivate the mitogen-activated protein kinase pathway and to interfere with differentiation of secretory cells.

Aging↗
PubMedDate not supplied

Distribution of mouse sulfated glycoprotein-1 (prosaposin) in the testis and other tissues.

Mouse sulfated glycoprotein-1 (SGP-1) is the homologue of rat SGP-1 and human prosaposin. Rat SGP-1 is one of the major secretory products of rat Sertoli cells in culture. Human prosaposin is the precursor of four lysosomal saposins, termed A, B, C, and D, that are generated by limited proteolysis. Saposins are sphingolipid-binding proteins that function as activators for lysosomal enzymes involved in sphingolipid hydrolysis of the former. Recently, we have generated a cDNA encoding the mouse SGP-1 by polymerase chain reaction amplification of a mouse testicular Uni-Zap XR cDNA library with two synthetic oligonucleotide primers and have used it as a probe for examining the tissue distribution of SGP-1 mRNA. We have also studied the distribution of the translation product of SGP-1 mRNA in the same tissues. The analysis demonstrated that SGP-1 is expressed ubiquitously in all tissues examined. This investigation showed that, in mouse testis, two forms of SGP-1 exist: a 70-kDa secreted protein and a 65-kDa protein corresponding to the lysosomal form of SGP-1, which may be involved in the generation of saposins. Light microscope immunocytochemistry with anti-SGP-1 antibody demonstrated that, in the mouse seminiferous tubules, the translation product of SGP-1 mRNA is expressed in Sertoli cells but not in germinal cells. Electron microscope immunogold labeling with anti-SGP-1 antibody yielded a strong reaction on lysosomes and phagolysosomes containing residual bodies but not on endosomes or luminal residual bodies. These results demonstrate that SGP-1 is not internalized from the lumen but is targeted directly to the lysosomes from the Golgi apparatus. Immunoblotting also confirmed the existence of a secreted form of testicular SGP-1 delivered to the lumen of the seminiferous tubules. The production of a secreted and a lysosomal form of SGP-1 by Sertoli cells indicates that this protein plays a multifunctional role. This study also suggests that the lysosomal form of SGP-1 may be involved in the degradation of membrane glycolipids from residual bodies phagocytosed by Sertoli cells.

Animals↗
PubMedDate not supplied

Mouse testicular sulfated glycoprotein-1: sequence analysis of the common backbone structure of prosaposins.

We have generated a cDNA encoding the mouse sulfated glycoprotein-1 (SGP-1) by polymerase chain reaction amplification of a mouse testicular Uni-Zap XR cDNA library with two synthetic oligonucleotide primers. A positive signal of 1,959 bases was isolated and subcloned into the pGEM-T. Sequence analysis showed a near identical nucleotide and amino acid similarity to mouse prosaposin cDNA. A few amino acid differences were found, and they may represent strain-specific heterogeneities. The cDNA has 88% amino acid identity to rat SGP-1 and 64% identity to human prosaposin. Prosaposin is the precursor of four lysosomal saposins (A, B, C, and D) that are generated by the proteolytic maturation of the former. Saposins are sphingolipid binding proteins that function as activators of lysosomal enzymes involved in sphingolipid hydrolysis. Northern blot analysis demonstrated that SGP-1 mRNA is transcribed in the seminiferous epithelium by Sertoli cells but not by germinal cells. Our results also demonstrated two forms of alternatively spliced testicular SGP-1 mRNA. This alternative splicing results in the inclusion or exclusion of exon 8, which encodes for three amino acid residues (QDQ) that are implicated in the sphingolipid binding affinity of saposin B. Sequence aligment indicates that all saposins share a common motif characterized by six conserved cysteines, a conserved N-linked glycosylation site, a conserved proline residue, and 15 positions that are characterized by large hydrophobic amino acids. These characteristics, together with similar secondary structure predictions and the predicted similar formation of three disulfide linkages, create a common framework of amino acids of three alpha helices enclosing an internal hydrophobic core for all saposins. The disulfide placement data, the hydropathy profile, and the presence of amphiphatic helices indicate that all saposins are stable proteins sharing similar secondary and tertiary structures.

Alternative Splicing↗