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Biomedical subjects

J Zhou

Publications and source records attributed to J Zhou.

At least 19 recordsLinked to original sources
PubMed2026

[Tafluprost/timolol fixed-dose combination versus tafluprost monotherapy for open-angle glaucoma and ocular hypertension: a multicenter, randomized, double-blind, parallel-group trial].

Objective: To evaluate the efficacy and safety of a preservative-free tafluprost/timolol maleate fixed-dose combination compared with preservative-free tafluprost monotherapy in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: This was a multicenter, randomized, double-blind, parallel-controlled clinical trial conducted across 25 centers, including the Eye & ENT Hospital of Fudan University, from January 2019 to November 2022. Patients diagnosed with OAG or OHT who required enhanced intraocular pressure (IOP) reduction after a 4-week washout period were enrolled. Participants were randomized 1&#x2236;1 to receive either tafluprost/timolol or tafluprost once daily for 3 months. The primary endpoint was the change from baseline in mean diurnal IOP (the average of measurements at 8:00, 10:00, and 16:00) at Month 3. Secondary endpoints included IOP changes at individual time points and the proportion of responders achieving predefined IOP reduction thresholds. Safety was assessed via the incidence of adverse events (AEs). Analysis of covariance (ANCOVA) using the Markov Chain Monte Carlo (MCMC) method was employed for the primary endpoint; superiority was established if the upper limit of the 95% confidence interval (CI) was<0 mmHg (1 mmHg=0.133 kPa). Continuous variables in secondary endpoints were compared using ANCOVA, and responder rates were analyzed using Fisher's exact test. Results: A total of 219 patients were enrolled (tafluprost/timolol group: n=110; tafluprost group: n=109). The primary efficacy analysis set included 215 patients (tafluprost/timolol: n=107; tafluprost: n=108). Baseline characteristics were well-balanced between the two groups. The majority of patients were male [127 (59.1%)] with a mean age of (44.80&#xb1;15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56&#xb1;3.44) mmHg in the tafluprost/timolol group and (5.36&#xb1;2.94) mmHg in the tafluprost group. After adjusting for baseline IOP, the between-group difference was -1.312 mmHg (95%CI: -2.010 to -0.696); as the upper limit was<0 mmHg, tafluprost/timolol demonstrated superior IOP-lowering efficacy to tafluprost. Responder rates for IOP reductions of&#x2265;15%,&#x2265;25%, and&#x2265;30% were significantly higher in the tafluprost/timolol group (P=0.016, 0.028, and 0.032, respectively). The incidence of ocular AEs was 20.0% (22/110) in the tafluprost/timolol group and 26.6% (29/109) in the tafluprost group. The most common AE was conjunctival hyperemia, occurring in 2.7% (3/110) and 8.3% (9/109) of the groups, respectively. Conclusion: Compared with preservative-free tafluprost monotherapy, the tafluprost/timolol combination provides significantly greater IOP reduction in patients with OAG and OHT, while maintaining a favorable safety profile.

Humans↗
PubMed1992

FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains.

Myogenin belongs to a family of myogenic helix-loop-helix (HLH) proteins that activate muscle transcription through binding to a conserved DNA sequence associated with numerous muscle-specific genes. Fibroblast growth factor (FGF) inhibits myogenesis by inactivating myogenic HLH proteins. We show that activated protein kinase C (PKC) can substitute for FGF and inhibit transcriptional activity of myogenic HLH proteins. In transfected cells, FGF induces phosphorylation of a conserved site in the DNA-binding domain of myogenin. This site is phosphorylated by PKC in vivo and in vitro and mediates repression of the myogenic program through a loss in DNA binding activity. A myogenin mutant lacking the PKC phosphorylation site is not repressed by FGF, confirming this site as a molecular target for FGF-dependent repression of muscle transcription. These results establish a direct link between the signal transduction pathways that inhibit myogenesis and the transcription factors directly activating muscle-specific genes.

Amino Acid Sequence↗
PubMed1992

The cpcE and cpcF genes of Synechococcus sp. PCC 7002. Construction and phenotypic characterization of interposon mutants.

The 3' region of the cpc operon of Synechococcus sp. PCC 7002 has been sequenced, transcriptionally characterized, and analyzed by interposon mutagenesis. The cpc operon contains six genes, 5' cpcB-cpcA-cpcC-cpcD-cpcE-cpcF 3', and gives rise to at least eight (more likely ten) discrete mRNA transcripts. The steady-state levels of transcripts for the cpcE and cpcF genes are very low and are estimated to represent only about 1-2% of the total transcripts arising from the cpc locus. The cpcE gene predicts a protein of 268 amino acid residues, whereas the cpcF gene predicts a protein of 205 amino acid residues. The deduced amino acid sequences of these proteins are about 50% identical and 70% similar to the predicted products of homologous genes which have been identified in other cyanobacterial cpc operons. Interposon insertion mutations were constructed in the cpcE and cpcF genes, and an interposon deletion mutation affecting both genes was constructed. The phenotypes of all mutant strains were similar. These strains were yellow-green in color, had doubling times approximately twice that of the wild-type strain, and failed to accumulate normal levels of phycocyanin. Further analyses indicated that these strains contained substantial amounts of apparently normal phycocyanin beta subunits; however the majority of the phycocyanin alpha subunit (about 90%) did not carry a phycocyanobilin chromophore. During serial subculturing of the mutant strains, suppressor mutations, which allowed cells to regain the ability to synthesize phycocyanin, arose at significant frequency. Based upon the results reported here, as well as those presented in the accompanying paper (Swanson, R. V., Zhou, J., Leary, J. A., Williams, T., de Lorimier, R., Bryant, D. A., and Glazer, A. N. (1992) J. Biol. Chem. 267, 16146-16154), we propose that the CpcE and CpcF polypeptides are the two subunits of a phycocyanobilin lyase specifically required for chromophorylation of the phycocyanin alpha subunit.

Amino Acid Sequence↗
PubMed1992

Characterization of phycocyanin produced by cpcE and cpcF mutants and identification of an intergenic suppressor of the defect in bilin attachment.

Mutants of the cyanobacterium Synechococcus sp. PCC 7002 constructed by the insertional inactivation of either the cpcE or cpcF gene produce low levels of spectroscopically detectable phycocyanin. The majority of the phycocyanin produced in these strains appears to lack the alpha subunit phycocyanobilin (PCB) chromophore (Zhou, J., Gasparich, G. E., Stirewalt, V. L., de Lorimier, R., and Bryant, D. A. (1992) J. Biol. Chem. 267, 16138-16145). Purification of the phycocyanin produced in the mutants revealed two fractions each with an aberrant absorption spectrum. Tryptic peptide maps of the major fraction showed that the alpha-84 PCB peptide was absent. The two PCB peptides derived from the beta subunit were normal. Tryptic digests of the less abundant phycocyanin fraction contained a family of bilin peptides derived from the alpha subunit. Several distinct bilin adducts were present. A major component was a mesobiliverdin adduct, a previously described product of the in vitro reaction of PCB and apophycocyanin. The same results were obtained with both the cpcE mutant and the cpcF mutant. In vitro reactions with PCB and the fractions containing apo alpha subunit showed that the alpha-84 bilin attachment site was unmodified and competent for adduct formation. Pseudo-revertants of both strains were observed to arise at high frequency. Analysis of the phycocyanin from a cpcE pseudo-revertant, which produced a near wild-type level of phycocyanin with alpha subunit carrying PCB, revealed a single amino acid substitution, alpha-Tyr129----Cys. This residue, which is conserved in all phycocyanins sequenced to date, forms part of the alpha-84 bilin binding site and lies within 5 A of alpha-Cys84. A mutated cpcA gene containing this substitution was constructed by site-directed mutagenesis and transformed, along with cpcB, into a cpcBAC deletion strain containing an insertionally inactivated cpcE. This strain produces high levels of phycocyanin and the majority of the alpha subunit carries PCB at alpha-Cys84.

Amino Acid Sequence↗
PubMed1992

Core mutations of Synechococcus sp. PCC 7002 phycobilisomes: a spectroscopic study.

Three cyanobacterial strains harboring mutations affecting phycobilisome (PBS) cores were studied using steady state absorption and fluorescence and time-resolved fluorescence. The apcF mutant, missing beta 18, and the apcDF mutant, missing both alpha APB and beta 18, showed only small spectroscopic differences from the wild-type strain; their PBS emission was blue shifted by 10 nm, whereas their absorption spectra and time-resolved fluorescence kinetics were virtually unchanged. The third mutant studied was the apcE/C186S mutant in which the chromophore-binding cysteine-186 in the LCM99 polypeptide has been substituted with serine. The apcE/C186S mutant contained a modified chromophore which significantly changed the spectroscopic properties of the PBS complex. The apcE/C186S PBS absorbed more than the wild-type strain at 705 nm, and the emission spectrum gave two peaks at 660 nm and 715 nm. The time-resolved kinetics of the apcE/C186S mutant PBS were also significantly altered from those of the wild-type strain.

Cyanobacteria↗
PubMed1992

Phycocyanin alpha-subunit phycocyanobilin lyase.

Phycobiliproteins, unlike other light-harvesting proteins involved in photosynthesis, bear covalently attached chromophores. The bilin chromophores are attached through thioether bonds to cysteine residues. The cyanobacterium Synechococcus sp. PCC 7002 has eight distinct bilin attachment sites on seven polypeptides, all of which carry the same chromophore, phycocyanobilin. When two genes in the phycocyanin operon of this organism, cpcE and cpcF, are inactivated by insertion, together or separately, the surprising result is elimination of correct bilin attachment at only one site, that on the alpha subunit of phycocyanin. We have overproduced CpcE and CpcF in Escherichia coli. In vitro, these proteins catalyze the attachment of phycocyanobilin to the alpha subunit of apophycocyanin at the appropriate site, alpha-Cys-84, to form the correct adduct. CpcE and CpcF also efficiently catalyze the reverse reaction, in which the bilin from holo-alpha subunit is transferred either to the apo-alpha subunit of the same C-phycocyanin or to the apo-alpha subunit of a heterologous C-phycocyanin. The forward and reverse reactions each require both CpcE and CpcF and are specific for the alpha-Cys-84 position. Phycocyanobilin is the immediate precursor of the protein-bound bilin.

Bile Pigments↗
PubMed1992

Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient.

We have generated and characterized cDNA clones providing the complete amino acid sequence of the human type IV collagen chain whose gene has been shown to be mutated in X chromosome-linked Alport syndrome. The entire translation product has 1,685 amino acid residues. There is a 26-residue signal peptide, a 1,430-residue collagenous domain starting with a 14-residue noncollagenous sequence, and a Gly-Xaa-Yaa-repeat sequence interrupted at 22 locations, and a 229-residue carboxyl-terminal noncollagenous domain. The calculated molecular weight of the mature alpha 5(IV) chain is 158,303. Analysis of genomic DNA from members of a kindred with Alport syndrome revealed a new HindIII cleavage site within the coding sequence of one of the cDNA clones characterized. The proband had a new 1.25-kilobase HindIII fragment and a lack of a 1.35-kilobase fragment, and his mildly affected female cousin had both alleles. The mutation which was located to exon 23 was sequenced from a polymerase chain reaction-amplified product, and shown to be a G----T change in the coding strand. The mutation changed the GGT codon of glycine 521 to cysteine. The same mutation was found in one allele of the female cousin. The results were confirmed by allele-specific hybridization analyses.

Adolescent↗
PubMed1992

Inactivated whole-virus vaccine derived from a proviral DNA clone of simian immunodeficiency virus induces high levels of neutralizing antibodies and confers protection against heterologous challenge.

We tested the ability of macaques vaccinated with inactivated whole simian immunodeficiency virus (SIV) to resist challenge with either homologous or heterologous cell-free uncloned SIV administered by the intravenous route. The vaccine virus was derived from a proviral DNA clone and thus was considered genetically homogeneous. Sixteen macaques received either hepatitis B surface antigen (n = 6) or the inactivated whole-SIV vaccine (n = 10) at weeks 0, 4, and 49 of the study. All SIV vaccine recipients developed high levels of homologous and heterologous neutralizing antibodies in response to vaccination. At the time of challenge (week 53), vaccinees were further stratified to receive either homologous (n = 10) or heterologous (n = 6) uncloned live SIV. The envelope glycoproteins of the homologous and heterologous challenge viruses were 94% and 81% identical to the vaccine virus, respectively. Regardless of challenge inoculum, all vaccinees in the control group (hepatitis B surface antigen) became infected, whereas all SIV vaccinees were protected against detectable infection. These data support the concept that an efficacious vaccine for HIV might be possible, and suggest that genetic variation of HIV might not be an insurmountable obstacle for vaccine development.

Animals↗
PubMed1992

Expression of c-erb B-2/neu proto-oncogene in human prostatic cancer tissues and cell lines.

Both amplification and overexpression of c-erb B-2/neu have been associated with the progression and possible prognosis of a number of human cancers. In this study, we demonstrated that c-erb B-2/neu may also play an important role in human prostate cancer. Our conclusion is based on the following observations: (1) A monoclonal antibody raised against a peptide sequence from the C-terminal domain of the human c-erb B-2/neu gene product reacted positively with 68.7% (11 of 16) of the human prostatic cancer tissue extracts analyzed by western blot procedure. These results were supported by the immunohistochemical staining of the prostatic cancer specimens; 80% (12 of 15) showed positive staining, primarily around the plasma membranes of the prostatic cancer cells. c-erb B-2/neu oncoprotein was not detectable in normal prostate tissues (five examined by immunohistochemical staining and three by western blotting) or in human benign prostatic hyperplasia (two examined by immunohistochemical staining and six by western blotting) and was expressed less abundantly with lower intensity in "normal" human prostate tissues adjacent to cancerous prostate tissue (5 of 12 examined by immunohistochemical staining). We observed no evidence of c-erb B-2/neu gene amplification in 10 fresh human prostatic cancer specimens examined by Southern blotting and in the cultured human prostatic cancer cell lines PC-3, DU-145, and LNCaP. (2) The c-erb B-2/neu protein was detected in both androgen-receptor-positive (LNCaP) and -negative (PC-3 and DU-145) human prostate cancer cell lines. Positive immunostaining of c-erb B-2/neu protein was found to be associated predominantly with the plasma membranes of PC-3 cells, but was also found to be widespread in the cytoplasmic region of the LNCaP cells and in the perinuclear region of the DU-145 cells. (3) Like prostate-specific antigen (PSA) expression, c-erb B-2/neu mRNA expression was also positively regulated by androgen in androgen-receptor-positive LNCaP cells in vitro and LNCaP tumors in vivo. When LNCaP tumors were grown in castrated male hosts, levels of c-erb B-2/neu and PSA mRNA expression decreased initially, but rebounded at 3 wk to levels comparable to those expressed by tumors maintained in intact adult male hosts.

Blotting, Northern↗
PubMed1992

Kinetic energy measurements of molecular ions ejected into an electric field by matrix-assisted laser desorption.

Measurements of kinetic energy distributions of molecular ions ejected into an extraction field by matrix-assisted laser desorption are reported. The measurements were made in a time-of-flight mass spectrometer with an electrostatic mirror by measuring the reflected signal as a function of the difference between the accelerating voltage and the voltage applied to the mirror. The molecular ions were found to have less kinetic energy than the extraction field alone would normally provide, i.e., we observed an energy deficit. Under conditions typical for a matrix-assisted laser desorption experiment, the deficit is about 24 eV for molecular ions of insulin. The size of the deficit increases with the intensity of the molecular ion signal, and the molecular weight of the protein; it is also larger for negative molecular ions than for positive molecular ions.

Animals↗
PubMed1992

Isolation and characterization of two wound-regulated tomato extensin genes.

Extensins comprise a family of structural cell wall hydroxyproline-rich glycoproteins in plants. Two tomato genomic clones, Tom J-10 and Tom L-4, were isolated from a tomato genomic DNA library by in situ plaque hybridization with extensin DNA probes. Tom J-10 encoded an extensin with 388 amino acid residues and a predicted molecular mass of 43 kDa. The Tom J-10 encoded extensin lacked a typical signal peptide sequence, but contained two distinct protein domains consisting of 19 tandem repeats of Ser-Pro4-Ser-Pro-Lys-Tyr-Val-Tyr-Lys at the amino terminus which were directly followed by 8 tandem repeats of the consensus sequence Ser-Pro4-Tyr3-Lys-Ser-Pro4-Ser-Pro at the carboxy terminus. RNA blot hybridization analysis with the Tom J-10 extensin probe demonstrated the presence of a 4.0 kb tomato stem mRNA which accumulated markedly in response to wounding. Tom L-4 encoded an extensin with 322 amino acid residues and a predicted molecular mass of 35 kDa. The Tom L-4 encoded extensin contained a typical signal peptide sequence at the amino terminus and was followed by at least 3 distinct domains. These domains consisted of an amino terminal domain containing several Lys-Pro and Ser-Pro4 repeat units, a central domain with repeats of the consensus sequence Ser-Pro2-5-Thr-Pro-Ser-Tyr-Glu-His-Pro-Lys-Thr-Pro, and a carboxy terminal domain containing repeats of the consensus sequence Ser-Ser-Pro4-Ser-Pro-Ser-Pro4-Thr-Tyr1-3. RNA blot hybridization analysis with the Tom L-4 extensin probe demonstrated the presence of a 2.6 kb tomato stem mRNA which accumulated in response to wounding.

Amino Acid Sequence↗
PubMed1992

Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species.

The two pathogenic species of Neisseria, N. meningitidis and N. gonorrhoeae, have evolved resistance to penicillin by alterations in chromosomal genes encoding the high molecular weight penicillin-binding proteins, or PBPs. The PBP 2 gene (penA) has been sequenced from over 20 Neisseria isolates, including susceptible and resistant strains of the two pathogenic species, and five human commensal species. The genes from penicillin-susceptible strains of N. meningitidis and N. gonorrhoeae are very uniform, whereas those from penicillin-resistant strains consist of a mosaic of regions resembling those in susceptible strains of the same species, interspersed with regions resembling those in one, or in some cases, two of the commensal species. The mosaic structure is interpreted as having arisen from the horizontal transfer, by genetic transformation, of blocks of DNA, usually of a few hundred base pairs. The commensal species identified as donors in these interspecies recombinational events (N. flavescens and N. cinerea) are intrinsically more resistant to penicillin than typical isolates of the pathogenic species. Transformation has apparently provided N. meningitidis and N. gonorrhoeae with a mechanism by which they can obtain increased resistance to penicillin by replacing their penA genes (or the relevant parts of them) with the penA genes of related species that fortuitously produce forms of PBP 2 that are less susceptible to inhibition by the antibiotic. The ends of the diverged blocks of DNA in the penA genes of different penicillin-resistant strains are located at the same position more often than would be the case if they represent independent crossovers at random points along the gene. Some of these common crossover points may represent common ancestry, but reasons are given for thinking that some may represent independent events occurring at recombinational hotspots.

Base Sequence↗
PubMed1992

Alport syndrome: a genetic study of 31 families.

Thirty one families with Alport syndrome including 3 families with associated syndromes were studied. The location of the COL4A5 gene, responsible for the Alport syndrome, was determined by linkage analysis with eight probes of the Xq arm and by a radiation hybrid panel. Concordant data indicated the localization of the Alport gene between DXS17 and DXS11. Four deletions and one single base mutation of the COL4A5 gene were detected. Homogeneity tests failed to show any evidence of genetic heterogeneity superimposed on clinical heterogeneity for ophthalmic signs and end-stage renal disease age.

Adolescent↗
PubMed1992

Oleanane glycosides from Glycyrrhiza yunnanensis roots.

From the roots of Glycyrrhiza yunnanensis, collected in Yunnan, China, six new oleanane-type triterpene glycosides named yunganosides A1, B1, C1, D1, E2 and F2 were isolated together with hypaphorine. The structures of these glycosides were established by spectroscopic and chemical means.

Carbohydrate Sequence↗
PubMed1992

Definition of linear antigenic regions of the HPV16 L1 capsid protein using synthetic virion-like particles.

Mice of three haplotypes (H-2d, H-2b, and H-2d/b) were immunized with synthetic HPV16 virus-like particles (VLPs), produced using a vaccinia virus doubly recombinant for the L1 and L2 proteins of HPV16. The resultant anti-VLP antisera recognized HPV16 capsids by ELISA assay and baculovirus recombinant HPV16 L1 and L2 protein on immunoblot. Overlapping peptides corresponding to the HPV16 L1 amino acid sequence were used to define the immunoreactive regions of the L1 protein. The majority of the L1 peptides were reactive with IgG from the mice immunized with the synthetic HPV16 capsids. A computer algorithm predicted seven B epitopes in HPV16 L1, five of which lay within peptides strongly reactive with the murine antisera. The murine anti-VLP antisera failed to react with the two peptides recognized by anti-HPV16L1 monoclonal antibodies raised by others against recombinant L1 fusion protein. We conclude that the immunoreactive epitopes of HPV16 defined using virus-like particles differ significantly from those defined using recombinant HPV16 L1 fusion proteins, which implies that such fusion proteins may not be the antigens to look for HPV16L1 specific immune responses in HPV-infected patients.

Amino Acid Sequence↗
PubMed1992

The vaccinia virus K2L gene encodes a serine protease inhibitor which inhibits cell-cell fusion.

In certain circumstances, cells infected with vaccinia virus (VV) undergo fusion, but this does not occur in tissue cultures infected with wild-type VV. The VV genome includes three genes (B24R, B13R, and K2L) encoding polypeptides that are structurally related to members of the plasma serine proteases inhibitor (SPI) superfamily. In this study, we demonstrate by deleting these genes singly or in combination that the K2L gene encoding SPI-3, but not the B24R or B13R genes encoding SPI-1 and SPI-2, inhibits cell-cell fusion in VV-infected cells. A VV-encoded hemagglutinin (HA) has previously been demonstrated to inhibit cell-cell fusion, but fusion-promoting VVs with K2L gene deletions had normal expression and cellular location of the VV HA. As both HA and SPI-3 independently inhibit cell-cell fusion in VV-infected cells, there must be at least two fusion-promoting mechanisms encoded by VV. These may play different roles in virus-cell fusion and in cell-cell fusion after VV infection.

Animals↗
PubMed1992

muI Na+ channels expressed transiently in human embryonic kidney cells: biochemical and biophysical properties.

We describe the transient expression of the rat skeletal muscle muI Na+ channel in human embryonic kidney (HEK 293) cells. Functional channels appear at a density of approximately 30 in a 10 microns 2 patch, comparable to those of native excitable cells. Unlike muI currents in oocytes, inactivation gating is predominantly (approximately 97%) fast, although clear evidence is provided for noninactivating gating modes, which have been linked to anomalous behavior in the inherited disorder hyperkalemic periodic paralysis. Sequence-specific antibodies detect a approximately 230 kd glycopeptide. The majority of molecules acquire only neutral oligosaccharides and are retained within the cell. Electrophoretic mobility on SDS gels suggests the molecules may acquire covalently attached lipid. The channel is readily phosphorylated by activation of the protein kinase A and protein kinase C second messenger pathways.

Animals↗