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B Zhou

Publications and source records attributed to B Zhou.

At least 55 records · Page 3Linked to original sources

Genetic, structural and functional diversities of human complement components C4A and C4B and their mouse homologues, Slp and C4.

The complement protein C4 is a non-enzymatic component of the C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. The covalent binding of C4 to immunoglobulins and immune complexes (IC) also enhances the solubilization of immune aggregates, and the clearance of IC through complement receptor one (CR1) on erythrocytes. Human C4 is the most polymorphic protein of the complement system. In this review, we summarize the current concepts on the 1-2-3 loci model of C4A and C4B genes in the population, factors affecting the expression levels of C4 transcripts and proteins, and the structural, functional and serological diversities of the C4A and C4B proteins. The diversities and polymorphisms of the mouse homologues Slp and C4 proteins are described and contrasted with their human homologues. The human C4 genes are located in the MHC class III region on chromosome 6. Each human C4 gene consists of 41 exons coding for a 5.4-kb transcript. The long gene is 20.6 kb and the short gene is 14.2 kb. In the Caucasian population 55% of the MHC haplotypes have the 2-locus, C4A-C4B configurations and 45% have an unequal number of C4A and C4B genes. Moreover, three-quarters of C4 genes harbor the 6.4 kb endogenous retrovirus HERV-K(C4) in the intron 9 of the long genes. Duplication of a C4 gene always concurs with its adjacent genes RP, CYP21 and TNX, which together form a genetic unit termed an RCCX module. Monomodular, bimodular and trimodular RCCX structures with 1, 2 and 3 complement C4 genes have frequencies of 17%, 69% and 14%, respectively. Partial deficiencies of C4A and C4B, primarily due to the presence of monomodular haplotypes and homo-expression of C4A proteins from bimodular structures, have a combined frequency of 31.6%. Multiple structural isoforms of each C4A and C4B allotype exist in the circulation because of the imperfect and incomplete proteolytic processing of the precursor protein to form the beta-alpha-gamma structures. Immunofixation experiments of C4A and C4B demonstrate > 41 allotypes in the two classes of proteins. A compilation of polymorphic sites from limited C4 sequences revealed the presence of 24 polymophic residues, mostly clustered C-terminal to the thioester bond within the C4d region of the alpha-chain. The covalent binding affinities of the thioester carbonyl group of C4A and C4B appear to be modulated by four isotypic residues at positions 1101, 1102, 1105 and 1106. Site directed mutagenesis experiments revealed that D1106 is responsible for the effective binding of C4A to form amide bonds with immune aggregates or protein antigens, and H1106 of C4B catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens. The expression of C4 is inducible or enhanced by gamma-interferon. The liver is the main organ that synthesizes and secretes C4A and C4B to the circulation but there are many extra-hepatic sites producing moderate quantities of C4 for local defense. The plasma protein levels of C4A and C4B are mainly determined by the corresponding gene dosage. However, C4B proteins encoded by monomodular short genes may have relatively higher concentrations than those from long C4A genes. The 5' regulatory sequence of a C4 gene contains a Spl site, three E-boxes but no TATA box. The sequences beyond--1524 nt may be completely different as the C4 genes at RCCX module I have RPI-specific sequences, while those at Modules II, III and IV have TNXA-specific sequences. The remarkable genetic diversity of human C4A and C4B probably promotes the exchange of genetic information to create and maintain the quantitative and qualitative variations of C4A and C4B proteins in the population, as driven by the selection pressure against a great variety of microbes. An undesirable accompanying byproduct of this phenomenon is the inherent deleterious recombinations among the RCCX constituents leading to autoimmune and genetic disorders.

Amino Acid Sequence↗

A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.

Hallervorden-Spatz syndrome (HSS) is an autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals iron deposits in the basal ganglia. In this respect, HSS may serve as a model for complex neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, Huntington disease and human immunodeficiency virus (HIV) encephalopathy, in which pathologic accumulation of iron in the brain is also observed. Thus, understanding the biochemical defect in HSS may provide key insights into the regulation of iron metabolism and its perturbation in this and other neurodegenerative diseases. Here we show that HSS is caused by a defect in a novel pantothenate kinase gene and propose a mechanism for oxidative stress in the pathophysiology of the disease.

Amino Acid Sequence↗

Octamer proteins inhibit IL-4 gene transcription in normal human CD4 T cells.

The balance of Th1 (eg, interleukin-2 (IL-2)) and Th2 (eg, IL-4) cytokines produced by CD4 T cells markedly influences the outcome of the adaptive immune response. Although octamer transcription factor proteins increase IL-2 transcription in T cells, their role in IL-4 gene transcription remains controversial. We have previously shown and now confirm that the proximal octamer binding site of the human IL-4 promoter, which separates the two most proximal NFAT binding sites, is bound prior to, but not after, activation in vivo. Since these two NFAT sites are essential for optimal IL-4 promoter activity, this suggested that prior engagement by octamer proteins might prevent adjacent NFAT binding and inhibit IL-4 gene transcription. In support of this hypothesis, here we show that NFAT proteins are unable to bind to a combined octamer/NFAT site unless the octamer proteins are competed away. Moreover, activity of an IL-4 reporter gene mutated in the proximal octamer binding site is increased compared to the wild-type promoter in human peripheral blood CD4 T cells. In addition, over-expression of either Oct-1 or Oct-2 decreased wild-type IL-4 promoter activity, while increasing IL-2 promoter activity. No decrease in promoter activity was seen when Oct-1 or Oct-2 was over-expressed with the octamer-mutant IL-4 reporter gene. Thus, octamer proteins are candidates to promote a Th1 rather than Th2 pattern of cytokine gene expression by activated CD4 T cells.

Binding Sites↗

Stroke volume does not plateau during graded exercise in elite male distance runners.

UNLABELLED: Stroke volume (SV) responses during graded treadmill exercise were studied in 1) elite male distance runners (N = 5), 2) male university distance runners (N = 10), and 3) male untrained university students (N = 10). METHODS: Cardiac output (Q) and SV were determined by a modified acetylene rebreathing procedure. RESULTS: There were no differences in SV responses among the three groups during the transition from rest to light exercise (P > 0.05). However, the rates of change of SV during light to maximal exercise in untrained subjects (slope = -0.1544 mL x beat(-1)) and university distance runners (slope = 0.1041) did not change, whereas it dramatically increased (P < 0.001) in elite distant runners (slope = 0.6734). Moreover, the elite distance runners showed a further slope increase in SV when heart rate was above 160 bpm, which resulted in an average maximal SV of 187 +/- 14 mL x beat(-1) compared with 145 +/- 8 and 128 +/- 14 mL x beat(-1) in the university runners and untrained students, respectively (P < 0.001). Similarly, max Q reached 33.8 +/- 2.3, 26.3 +/- 1.7, and 21.3 +/- 1.5 L x min(-1) in the three groups, respectively (P < 0.001). On the other hand, there was a nonsignificant tendency for maximal arteriovenous oxygen content difference to be lower in the elite athletes compared with the other groups. CONCLUSION: Results from university distance runners and untrained university students support the classic observation that SV plateaus at about 40% of maximal oxygen consumption despite increasing intensity of exercise. In contrast, stroke volume in the elite athletes does not plateau but increases continuously with increasing intensity of exercise over the full range of the incremental exercise test.

Adult↗

Vesicular stomatitis virus G-pseudotyped lentivirus vectors mediate efficient apical transduction of polarized quiescent primary alveolar epithelial cells.

We investigated the use of lentivirus vectors for gene transfer to quiescent alveolar epithelial cells. Primary rat alveolar epithelial cells (AEC) grown on plastic or as polarized monolayers on tissue culture-treated polycarbonate semipermeable supports were transduced with a replication-defective human immunodeficiency virus-based lentivirus vector pseudotyped with the vesicular stomatitis virus G (VSV-G) protein and encoding an enhanced green fluorescent protein reporter gene. Transduction efficiency, evaluated by confocal microscopy and quantified by fluorescence-activated cell sorting, was dependent on the dose of vector, ranging from 4% at a multiplicity of infection (MOI) of 0.1 to 99% at an MOI of 50 for AEC grown on plastic. At a comparable titer and MOI, transduction of these cells by a similarly pseudotyped murine leukemia virus vector was approximately 30-fold less than by the lentivirus vector. Importantly, comparison of lentivirus-mediated gene transfer from the apical or basolateral surface of confluent AEC monolayers (R(t) > 2 kOmega. cm(2); MOI = 10) revealed efficient transduction only when VSV-G-pseudotyped lentivirus was applied apically. Furthermore, treatment with EGTA to increase access to the basolateral surface did not increase transduction of apically applied virus, indicating that transduction was primarily via the apical membrane domain. In contrast, differentiated tracheal epithelial cells were transduced by apically applied lentivirus only in the presence of EGTA and at a much lower overall efficiency (approximately 15-fold) than was observed for AEC. Efficient transduction of AEC from the apical cell surface supports the feasibility of using VSV-G-pseudotyped lentivirus vectors for gene transfer to the alveolar epithelium and suggests that differences exist between upper and lower airways in the polarity of available receptors for the VSV-G protein.

Animals↗

Human ribonucleotide reductase M2 subunit gene amplification and transcriptional regulation in a homogeneous staining chromosome region responsible for the mechanism of drug resistance.

In our previous publication it was shown that a Gemcitabine-resistant KBGem clone derived from step-wise exposure to Gemcitabine resulted in overexpression of the human Ribonucleotide Reductase M2 subunit (hRRM2) mRNA and protein (Goan et al., 1999). In this study we confirm these results and show that the hRRM2 gene amplification arises in a homogeneous staining region (hsr) derived from chromosome translocation. The hydroxyurea-resistant clone (KBHURs) was studied as a comparison. PCR analysis of the hRRM2 gene promoter confirmed the amplification. Northern and Western blots were further employed to confirm the gene amplification and hRRM2 mRNA and protein expression were compatible with the level of drug resistance. Cells synchronized by serum starvation and then returned to serum-containing growth conditions showed a rapid induction of high levels of transcription of the hRRM2 gene. To clarify whether expression of hRRM2 mRNA was regulated at a transcriptional level, several transcription factors, including AP-1, Sp1, AP-2, CREB, NF-kappa B, and OCT1, were examined by gel-shift assay. Interestingly, the KBGem clone was regulated by different transcription factors than the KBHURs clone. Compared to the wild-type KB cells (KBwt), the KBGem clone exhibited a different binding pattern for Sp1 and NF-kappa B. The KBHURs clone, however, demonstrated a unique binding pattern with AP-1 and CREB, different from the KBwt control as well as the KBGem clone. Therefore, we conclude that the drug-resistant phenotype is associated with human RRM2 gene amplification from a homogeneous staining chromosome region and altered transcription regulation. Each clone demonstrated a unique pattern of transcription factor binding that may play a vital role in the mechanism of drug resistance.

Chromosome Banding↗

Characterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses.

Ribonucleotide Reductase (RR) is a rate-limiting enzyme in DNA synthesis and repair consisting of two subunits, M1 and M2. RRM2 plays a role in cell proliferation, tumorgenicity, metastasis and drug resistance. To better understand the regulation of RRM2, we have sequenced the entire human RRM2 gene. Approximately 10.3 kb of genomic DNA was sequenced and deposited to GenBank (accession number AY032750). Intron/exon junctions were identified and the gene was found to consist of ten exons. Two transcription initiation sites were identified and correspond to mRNA transcripts of 3.4 kb and 1.65 kb. Deletion analysis of the 5'-flanking region showed that there was promoter activity consistent with the presence of two separate promoters driving expression of the two RRM2 transcripts. A thorough analysis of the genomic sequence and promoter regions of the RRM2 gene will provide insight into the processes involved in tumor transformation and drug resistance.

Base Sequence↗

[The relationship of variability of blood pressure with cardiac structure and functions in hypertension].

OBJECTIVE: To study the relationship of variability of blood pressure with cardiac structure and functions in essential hypertension. METHODS: A hundred and ten patients suffered from essential hypertension were divided into two groups according whether having left ventricular hypertrophy. The characteristics of overload and variability of blood pressure in both groups were analysed and several indexes on cardiac structure and function were compared between two groups. RESULTS: Both groups showed significant differences in the mass of left ventricle (LVM), the mass index (LVMI) of left ventricle, the thickness of interventricular septum (IVS), posterior wall of left ventricle (LVPW) and relative wall thickness (RWT) except for hypertensive ages. The ratio of E/A in both groups was significantly decreased. The rate of SBP load (SBPLO) both at day and night, the level of SBP in 24 hours and reductive rate of SBP at night (nSBPrr), the variabilities of systolic blood pressure (SBPV) and mean arterial pressure (MAPV) as well as hypertensive vascular overload index (HTNVOI) in two groups were obviously different. CONCLUSIONS: 1) In early stage, the diastolic cardiac function in essential hypertension was damaged. 2) The happeness of left ventricular hypertrophy in essential hypertension was not only associated with the degrees and types of vascular overload, the increased variabilities of systolic blood pressure and mean arterial pressure, reversely with the reductive rate of SBP at night as well, but feebly with hypertensive-age. 3) As a low awareness, hypertensive-age was unreliable in the recollection. 4) Age was also a risk factor of left ventricular hypertrophy in essential hypertension.

Adult↗

Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats.

AIM: To study the antifibrotic effects of matrine in vitro a nd in vivo. METHODS: Rat hepatic stellate cell HSC-T6 and mouse fibroblast cell NIH3T3 proliferation stimulated with serum and platelet-derived growth factor (PDGF) was measured b y crystal violet staining assay. Collagen synthesis stimulated with serum and transforming growth factor beta1 (TGF-beta1) was determined by [3H]proline incorporation. Liver fibrosis was induced by carbon tetrachloride (CCl4) in rats an d evaluated with plasma hyaluranic acid level and hepatic hydroxyproline content. RESULTS: Matrine (1-2 mmol/L) markedly reduced serum-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells. PDGF-driven proliferative activity and TGF-beta1-driven collagen synthesis in HSC-T6 cel ls were attenuated by matrine (0.25-2 mmol/L) in a concentration-dependent manner. In vivo matrine (50 mg/kg and 100 mg/kg) significantly decreased serum hyaluranic acid levels and hepatic hydroxyproline contents in rats treated with CCl4. CONCLUSION: Inhibition of PDGF and TGF-beta1 actions on hepatic stellate cell by matrine might provide a possible mechanism of its antifibrotic activities.

3T3 Cells↗

Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages.

AIM: To study the effects of matrine (Mat) on production and actions of fibrogenic cytokines from mouse peritoneal macrophages. METHODS: Mouse peritoneal macrophages were primed with calcimycin 1 micromol/L for 8 h then elicited by lipopolysaccharides (LPS) 100 microg/L for 6 h to induce fibrogenic cytokines. Proliferative and collagen stimulating activity in the macrophage culture supernatants was determined by crystal violet staining assay and [3H]-proline incorporation assay using rat hepatic stellate HSC-T6 cell or mouse fibroblast NIH3T3 cell. Transforming growth factor beta (TGFbeta) activity was measured by [3H]-thymidine incorporation assay using Mv-1-Lu mink lung epithelial cell. RESULTS: Mat (0.5-2 mmol/L) was shown to significantly inhibit LPS-induced collagen stimulating activities and TGFbeta production (P < 0.01) whereas did not inhibit proliferative activities induced by macrophages. Macrophage conditioned medium (MCM)-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells were attenuated by Mat (0.5-2 mmol/L) in a concentration-dependent manner. CONCLUSION: Antifibrotic effects of Mat on hepatic stellate cells may be related to reduction of fibrogenic cytokine production and blockade of their actions.

Alkaloids↗

[Pathogens of transmitted disease in the pathogenesis of acute pelvic inflammatory disease].

OBJECTIVE: To study the pathogenesis of pathogens of sexually transmitted disease (STD) in acute pelvic inflammatory disease (PID). METHODS: Neisseria gonorrhoeae, chlamydia trchomatis, ureaplasma urealyticum were cutured respectively in 130 patients with acute PID. RESULTS: The pathogens of STD had been found in 55 patients. The detective rate of Neisseria gonorrhoeae was 6.9% (9/130), about half of them were mixed infection; the detective rate of chlamydia trachomatis was 4.6% (6/130), all of them were mixed infection; the positive percentage of ureaplasma urealyticum was 37.7% (49/130), one third of them were mixed infection. CONCLUSION: The pathogens of STD might cause acute PID or only play a synergetic role in it.

Acute Disease↗

[Prevalence of dementia in Shanghai urban and rural area].

OBJECTIVE: To study the prevalence and epidemiological characteristics of dementia and their major types in people aged 55 years and old in urban and rural area, Shanghai. METHODS: A sample with 17,018 residents aged 55 years and above from 22 urban and 14 rural communities was drawn through a stratified multiple stage cluster sampling. A door-to-door three-phase procedure was used to investigate the prevalence of dementia. In 1997 and 1998, A brief memory testing by MMSE was administered to all participants. In phase 2, those who scored below the cutoff points and four percent of those whose score was in the normal range were interviewed to identify dementia through a set of diagnostic examinations according to the DSM-IV criteria. In phase 3, a follow-up program was conducted in 1998 for all persons who was involved in phase 2 to identify those with Alzheimer's dementia (AD) and vascular dementia (VaD) by NINCDS-ADRDA and NINDS-AIREN criteria. RESULTS: Of the targeted sample, 15,910 (94.2%) were interviewed. The overall prevalence of dementia was 3.0% in individuals aged 55 years and above, 4.32% in those aged 65 years old and 5.29% in those aged 70 years and above. The age-adjusted prevalence rates of dementia were 2.03%, 3.78% and 5.48% respectively among the age groups mentioned above. For AD the age-adjusted prevalence rates were 1.37%, 2.71% and 4.13% for individuals in above age groups. Of all types of dementia, AD was accounted 72%, followed by VaD the second. The prevalence of AD was 1.41% in man comparing to 2.78% in woman. The age-specific prevalence of AD increased with age. CONCLUSION: The prevalence of dementia was 3.0% in individuals aged 55 years in urban and rural areas in Shanghai. Alzheimer's disease was more frequent than VaD.

Aged↗

[RFLP analysis of wheat-L. racemosus translocation lines].

A number of wheat-L. racemosus translocation lines were developed by irradiation, pollen culture and gametocidal chromosome methods. In order to identify homozygous translocation lines and determine the exact location of the breakpoints involved in the translocations, 67 probes genetically or physically mapped previously on wheat chromosomes belonging to seven homoeologous groups were used for RFLP analysis. Three homozygous translocation lines were identified: T1BL.7Lr # 1S, T4BS.4BL-7Lr # 1 and T6AL.7Lr # 1S. In lines T1BL.7Lr # 1S and T6AL.7Lr # 1S, the breakpoint of chromosome 7Lr # 1 was located in the short arm between the area marked by clone MWG808 and that of ABG476.1, and the breakpoints of chromosomes 1B and 6A were both located near the centromere. In line T4BS.4BL-7Lr # 1S, the breakpoint of chromosome 7Lr # 1 was located in the short arm between the area marked by clone BCD349 and that of CDO595, the breakpoint of chromosome 4B was located in the long arm between the area marked by clone CDO541 and that of PSR164.

Polymorphism, Restriction Fragment Length↗

[Effect of fly ash-filtered mud mixture on soil properties and radish yield and quality].

Based on pot culture experiment, the effect of fly ash-filtered mud mixture on soil biochemical properties, radish yield and its quality, and heavy metal accumulation in both soil and radish was examined. The mixture was made by mixing fly ash and filtered mud in proportion 1:1(w/w) and adding small amount of inorganic fertilizer. Its Cd, Pb, Cr, As and Hg contents were much lower than those requested by state control criteria. After applying this mixture in a definite amount, no significant accumulation of heavy metals was found in both soil and radish, the pollution index of heavy metals was < 1, the quantities of soil bacteria increased notably, and the activities of soil urease, phosphates and cellulosase also raised significantly. The application of the mixture promoted radish growth and its development and metabolism. The reducing sugar and vitamin C in radish also increased markedly. The results indicated that the use of adequate amounts of the mixture did not cause any obvious heavy metal pollution in both soil and radish, but could improve soil fertility, and raise radish yield and its quality remarkably.

Agriculture↗

[Detection and analysis of SYT-SSX fusion gene in synovial sarcoma].

OBJECTIVE: To demonstrate that a characteristic SYT-SSX fusion gene resulting from chromosomal translocation t (X; 18) (p11; q11) was detectable in archival paraffin-embedded synovial sarcoma tissues. METHODS: SYT-SSX fusion transcripts in 20 synovial sarcomas (histologic subtypes, 15 monophasic and 5 biphasic) were detected and analyzed by the reverse-transcriptase polymerase chain reaction and compared with the results from relevant pathological data. RESULTS: A specific SYT-SSX RT-PCR product was found in 19 of 20 (95%) synovial sarcomas tested and of the 13 tumors containing SYT-SSX2, 10 were monophasic. CONCLUSION: SYT-SSX fusion transcripts are considered as a defining diagnostic marker of synovial sarcomas and the subtypes of SYT-SSX fusion transcripts (SYT-SSX1 and SYT-SSX2) may yield prognostic information.

Adolescent↗

[The effects of iron supplementation on auditory brain-stem response with iron deficiency anemia in rats].

OBJECTIVE: To evaluate the therapeutic methods of sensorineural hearing loss with iron deficiency anemia and their effects. METHOD: Sixty-eight Wistar rats were randomly divided into 3 groups: Group A (iron deficiency group A) 24 rats, group B (iron deficiency group B) 24 rats and group C (control group) 20 rats. Group A and B were fed with iron deficiency diet for 6 weeks. By analyzing ABR and DPOAE, hearing loss was detected in group A and B. Then, group A was given iron supplementation diet and hyperbaric oxygen therapies, and group B was given iron supplementation diet only. RESULT: The auditory thresholds and period latencies (PL) of I waves of ABR and DPOAE amplitude in 2 kHz and 3 kHz within group A and B were significantly different before and after treatment (P < 0.05). But the effects of treatment between these two groups had not significant differences (P > 0.05). CONCLUSION: It suggested that good results can be obtained by early iron supplementation in iron deficiency hearing loss cases. Hyperbaric Oxygen therapy may not be necessary.

Anemia, Iron-Deficiency↗

[The infiltration and activation stage of eosinophils in nasal polyps].

OBJECTIVE: To assess the infiltration and activation of eosinophils in nasal polyps. METHOD: Nasal polyps from sixteen patients were investigated. The samples were stained with Chromotrope 2R histochemical and ABC immunohistochemical methods. RESULT: The majority of eosinophils in nasal polyps were activated, and there were no significant differences in the numbers of total eosinophils (Chromotrope 2R positive cells) and activated eosinophils (EG2 positive cells) between allergic and nonallergic patients. CONCLUSION: Eosinophilia is a prominent histologic feature of nasal polyps which indicates that the activated eosinophils may play vital role in the pathogenesis of nasal polyps.

Adult↗

[Study on some metal elements levels and the T lymphocyte subset of the peripheral lymphocytes in patients with nasopharyngeal carcinomas].

OBJECTIVE: To study some metal elements levels and T lymphocyte subset of the peripheral lymphocytes in patients with nasopharyngeal. METHOD: Metal elements in the patients with nasopharyngeal and normal control were detected by the Atomic Absorption Spectrometer (Flame SHIMATZV.JAPAN). T lymphocyte subset were detected by the flow cytometry (FCM). RESULT: The level of copper was significantly higher and the level of zinc was significantly lower in patients with nasopharyngeal carcinomas than those in normal control group (P < 0.01 and < 0.05 respectively). The number of CD3/CD4 cell in the patients group were less than those in normal group(P < 0.01). CONCLUSION: The results of correlative analysis showed that there was a significant correlationship between the number of CD4 cells and levels of copper in peripheral lymphocytes of the patients group.

Adult↗