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Biomedical subjects

Z Gu

Publications and source records attributed to Z Gu.

At least 91 records · Page 5Linked to original sources

[Energy dispersive X-ray analysis in studying the permeability of blood-brain barrier caused by lead in rats].

OBJECTIVE: To observe the changes in permeability of blood-brain barrier caused by lead in rats. METHODS: Rats were fed with drinking water containing 10 and 30 mg/L of lead for three months. Electron microscopy lanthanum nitrate-tracing and electron probe-energy dispersive X-ray (EDX) analysis were used to observe the distribution of lead in different cells of bilateral sides of capillaries of cerebral cortex and the changes in their permeability. RESULTS: There was significant difference in blood lead levels between the rats with drinking water of 10 mg/L lead and the controls, but only a peak of lead, L(alpha), could appear in plasmalemma of endotheliaocyte endosurface in capillaries, and no any peak in the basement membrane of endotheliocyte of the outer-side, end feet of astrocytes and axons of neurons. Lanthanum nitrate-tracing showed changes in capillary permeability. But, in those with drinking water of 30 mg/L of lead, peak of lead, L(alpha) and M(alpha) could appear in all cells mentioned above. Meanwhile, lanthanum salt granules, which penetrated the cellular gaps of endothelia and seeped in the basement and its peripheral cells, could be found in certain sites of the capillaries with larger diameters. CONCLUSION: It suggests that the plasmalemma of endotheliocyte endosurface was the initial target in brain, where was affected by lead, and the consecutive endotheliocytes of blood vessels served as a blood-brain barrier to lead, although in a very weak action. A little bit accumulation of lead on the plasmalemma of endotheliocyte endosurface could cause damage in the close junction between endotheliocytes to spread to brain substance, same as the lanthanum tracing showed.

Animals↗

[Separation of levonorgestrel, progesterone and testosterone by micellar electrokinetic capillary chromatography].

Separation of levonorgestrel, progesterone and testosterone was achieved by using micellar electrokinetic capillary chromatography (MECC). A column of 53 cm (to the detector) x 50 microns i.d. uncoated fused-silica capillary (totally 68 cm in length) and an ultra-violet detector with fixed wavelength at 254 nm were used throughout all the experiments. MECC analysis was optimized by evaluating three different micelle-forming agents, the concentration of SDS and several of organic additives in a 10 mmol/L borate running buffer (pH 9.2). Complete separations were obtained with either 10%-20% acetonitrile or 20 mmol/L 2,6-dimethyl-beta-cyclodextrin (DM-beta-CD) as the modifier in buffer. When the acetonitrile volume fraction was in the range of 0-15%, the migration times of the three steroids increased with the acetonitrile volume fraction, but in the range of 15%-20% acetonitrile concentrations, the situation was opposite. This behavior of the steroids was attributed to the interaction of two opposite effects, an increased mobility due to decreased partition coefficient and a decreased electroosmotic flow (EOF). Both beta-cyclodextrin (beta-CD) and gamma-cyclodextrin (gamma-CD) were found to be inadequate for a satisfactory separation.

Chromatography, Micellar Electrokinetic Capillary↗

[The development of a kind of artificial articular cartilage-PVA-hydrogel].

In this study, the process included aqueous Poly (vinyl alcohol) solutions frozen at -20 degrees C for 6-12 h, and then thawed for 1-2 h. The same process was repeated 1-3 times. After the specimen was dehydrated in vacuum, a kind of artificial articular cartilage--PVA-hydrogel was made up. Subsequently, the micromorphology of PVA-hydrogel was observed by means of optical microscopy and SEM. DSC and mechanical tests were employed in ivestigating the influence of freesing, thawing, dehydrating and irradiating upon the crystallity and the mechanical properties of PVA-hydrogel.

Biocompatible Materials↗

[Evaluation of immunochromatographic test in the diagnosis of Plasmodium falciparum and Plasmodium vivax].

AIM: To evaluate the effectiveness of immunochromatographic test(ICT) in detecting Plasmodium falciparum and Plasmodium vivax in malaria endemic areas. METHODS: ICT was used to detect P. falciparum and P. vivax among patients with fever in the outpatient clinics by comparason with thick blood smear method. RESULTS: The sensitivity of ICT to detect P. falciparum and P. vivax was 96.7% and 90.4%, respectively. The specificity of ICT was 98.6%, and the coincidence rate was 94.7%. There is no cross reaction between P. falciparum and P. vivax. CONCLUSION: ICT could detect P. falciparum and P. vivax simutaneously, being more rapid and simple than blood smear method.

Animals↗

[A pilot study on malaria control by using a new strategy of combining strengthening infection source treatment and health education in mountainous areas of Hainan province].

AIM: To explore a new malaria control strategy that fits current epiodemiological condition and coincides with modern medicine model and the principle of cost-benefit. METHODS: The new strategy highlights the risk villages and risk population as the focal point and integrates health education with behavioral intervention. The main anti-malaria measures consists of carrying out health education in risk villages, giving mass drug administrations in risk population staying overnight in the mountain, following up malaria cases for implementing radical cure, but without using traditional residual spraying or impregnating bednets with insecticides. RESULTS: After having adopted the new strategy and taken the control measures, the people's knowledge about malaria increased to a higher level and the indices of malaria reduced to a lower level. The rate of bednet-using in the population was increased from 26.8% to 72.6%. The annual parasite incidence (API) of malaria was declined from 3.5% in 1994 to 1.1% in 1996 and 0.8% in 1997, and the API of falciparum malaria was declined from 1.0% to 0.3% and 0.3% respectively in the townships at the same time. The parasite rate(PR) of malaria was declined from 7.2% in May, 1995 to 2.1% in November, 1996 and 1.2% in October, 1997 and the PR of falciparum malaria was declined from 1.2% in May, 1995 to 0.1% in October, 1997. The proportion of villages without malaria cases was increased from 18.6% in 1994 to 54.2% in 1997, and the number of risk villages with a malaria incidence above 5% was reduced from 14 to 2 at the same time. The ratio of cost/benefit was 1:2.4 in 1995-1996 and 1:4.4 in 1997, showing a better economic benefit. CONCLUSION: The expectant result has been obtained, thereby providing new experience for the malaria control in the mountainous areas of Hainan Province.

China↗

[Aminoglycoside ototoxicity associated with mitochondrial DNA mutation].

OBJECTIVE: To confirm the effect of genetic susceptibility to aminoglycoside ototoxicity. METHOD: Mitochondrial DNA (mtDNA) from 62 members of 9 aminoglycoside induced deafness families was analysed by PCR-Restriction endonuclease digestion. RESULT: The nucleotide 1555A-->G mutation in 12S rRNA gene of mtDNA was identified in 20 members of 5 families. CONCLUSION: These findings indicate that this mutation is a molecular basis for genetic susceptibility to the ototoxic effect of aminoglycosides. The relationship between the audiovestibular changes and genetic susceptibility to aminoglycoside ototoxicity and the pathogenetic mechanism of susceptible deafness are discussed. The possibility that other gene mutations can also predispose to aminoglycoside ototoxicity is proposed.

Adolescent↗

Biphenylsulfonamide endothelin antagonists: structure-activity relationships of a series of mono- and disubstituted analogues and pharmacology of the orally active endothelin antagonist 2'-amino-N- (3,4-dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1, 1'-biphenyl]-2-sulfonamide (BMS-187308).

Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4'-position. Introduction of an amino group at the 2'-position also led to improved analogues. Combination of the optimal 4'-isobutyl substituent with the 2'-amino function afforded an analogue (20, BMS-187308) with improved ETA binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 micromol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.

Administration, Oral↗

Responses in the aged rat brain after total immunolesion.

In the present study, we compare the effects of cholinergic deafferentation of the hippocampus, cortex, and olfactory bulb of young and aged rats on nerve growth factor (NGF) protein levels in these areas. We also describe glial responses to intraventricular injections of the immunotoxin, 192 IgG-saporin in the aged. Choline acetyltransferase (ChAT) activity was dramatically decreased in the basal forebrain and target areas of the cholinergic basal forebrain neurons (CBFNs) in the young immunolesioned rats and to a lesser extent in their aged counterparts. After total immunolesion, NGF protein levels significantly increased in the hippocampus, cortex, and olfactory bulb of the young rats but not of the aged rats, except for small increases in the olfactory bulb after two weeks. After immunolesion NGF protein levels in the basal forebrain increased in young rats and less so in the aged rats. The total immunolesions had no effects on NGF and BDNF mRNA levels in the hippocampus and cortex. Two weeks after injection of the immunotoxin, the profiles of AChE- and p75NTR-positive cells significantly decreased in medial septum, vertical and horizontal limbs of diagonal band and nucleus basalis of Meynert. There was also an increase in microglia while but not astrocytes in the subnuclei of basal forebrain. In conclusion, 192 IgG-saporin was effective in producing cholinergic lesions in both young and aged rat brains, the lesion-induced NGF response was partially extinguished in the aged rat brains and immunolesions induced a microglial response in aged brain.

Afferent Pathways↗

Nip1p associates with 40 S ribosomes and the Prt1p subunit of eukaryotic initiation factor 3 and is required for efficient translation initiation.

Nip1p is an essential Saccharomyces cerevisiae protein that was identified in a screen for temperature conditional (ts) mutants exhibiting defects in nuclear transport. New results indicate that Nip1p has a primary role in translation initiation. Polysome profiles indicate that cells depleted of Nip1p and nip1-1 cells are defective in translation initiation, a conclusion that is supported by a reduced rate of protein synthesis in Nip1p-depleted cells. Nip1p cosediments with free 40 S ribosomal subunits and polysomal preinitiation complexes, but not with free or elongating 80 S ribosomes or 60 S subunits. Nip1p can be isolated in an about 670-kDa complex containing polyhistidine-tagged Prt1p, a subunit of translation initiation factor 3, by binding to Ni2+-NTA-agarose beads in a manner completely dependent on the tagged form of Prt1p. The nip1-1 ts growth defect was suppressed by the deletion of the ribosomal protein, RPL46. Also, nip1-1 mutant cells are hypersensitive to paromomycin. These results suggest that Nip1p is a subunit of eukaryotic initiation factor 3 required for efficient translation initiation.

Cell Division↗

Long term changes in brain cholinergic markers and nerve growth factor levels after partial immunolesion.

There are deficits in cholinergic basal forebrain neurons (CBFNs) in the aged brain and patients suffering Alzheimer's disease associated with a partial loss of the CBFNs. To mimic this partial loss and assess its long term effects on residual cholinergic activity and resultant target-derived nerve growth factor (NGF) levels, we produced a partial immunolesion to CBFNs with 192 IgG-saporin, an immunotoxin selectively taken up by p75NTR-bearing neurons. We measured two cholinergic markers, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, and NGF protein levels at 10 days, 1, 6 and 12 months postlesion. There were no significant changes in the cholinergic markers and the NGF protein levels in the sham-treated animal controls during the one year experiment. Ten days after 192 IgG-saporin treatment, ChAT activity decreased to 35-50% of controls in the olfactory bulb, hippocampus, and cortex. There was a minor but significant recovery of ChAT activity one year after the immunolesion in the hippocampus. Changes in AChE activity mirrored the ChAT changes but were less robust. There were transient increases in NGF protein levels in the hippocampus and cortex that returned to basal levels at 6 months and 12 months postlesion, respectively. In summary, partial immunolesions resulted in partial region-specific and time-dependent recoveries of cholinergic activity in the target areas of the basal forebrain after a partial elimination of CBFNs and a return to basal levels of NGF protein consistent with the hypothesis that the remaining CBFNs compensated for losses of ChAT and NGF due to changes in cholinergic innervation of basal forebrain target areas.

Acetylcholinesterase↗

Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates.

Resistance of HIV-1 reverse transcriptase (RT) to nucleoside analogs (e.g. AZT, ddC and 3TC) is conferred by various amino acid substitutions or combinations thereof on the RT molecule. The M184V mutation, that confers high and low-level resistance to 3TC and ddC, respectively, can restore sensitivity to AZT when introduced into RT against a background of AZT-resistance. The K65R mutation, that confers low level resistance to both 3TC and ddC, can also restore sensitivity to AZT. This information is of potential utility in choosing combinations of anti-viral drugs for clinical use. To explore this subject further, we have used an endogenous RT reaction to study mutated viruses containing M184V alone or M184V combined with each of the K65R, E89G or both the M41L and T215Y substitutions. Endogenous assays possess the advantage of utilizing genomic RNA as template in a reaction mixture that includes each of tRNALys.3 and viral nucleocapsid protein, necessary for specific initiation of reverse transcription, as well as all other viral proteins that might impact on this process. We now show that viruses containing both M184V and K65R displayed synergistic resistance to 3TC triphosphate (3TCTP), while the same combination yielded the same level of resistance to ddC triphosphate (ddCTP) as that manifested by K65R alone. The combination of M184V and E89G displayed synergistic resistance against ddCTP but not 3TCTP, while viruses containing only E89G were highly resistant to 3TCTP and displayed low-level resistance to ddCTP. The results show that endogenous RT assays can reveal variable synergistic, antagonistic, or neutral effects in regard to drug sensitivity, depending on the presence of specific amino acid substitutions in RT itself.

Anti-HIV Agents↗

The type I activin receptor ActRIB is required for egg cylinder organization and gastrulation in the mouse.

ActRIB is a type I transmembrane serine/threonine kinase receptor that has been shown to form heteromeric complexes with the type II activin receptors to mediate activin signal. To investigate the function of ActRIB in mammalian development, we generated ActRIB-deficient ES cell lines and mice by gene targeting. Analysis of the ActRIB-/- embryos showed that the epiblast and the extraembryonic ectoderm were disorganized, resulting in disruption and developmental arrest of the egg cylinder before gastrulation. To assess the function of ActRIB in mesoderm formation and gastrulation, chimera analysis was conducted. We found that ActRIB-/- ES cells injected into wild-type blastocysts were able to contribute to the mesoderm in chimeric embryos, suggesting that ActRIB is not required for mesoderm formation. Primitive streak formation, however, was impaired in chimeras when ActRIB-/- cells contributed highly to the epiblast. Further, chimeras generated by injection of wild-type ES cells into ActRIB-/- blastocysts formed relatively normal extraembryonic tissues, but the embryo proper developed poorly probably resulting from severe gastrulation defect. These results provide genetic evidence that ActRIB functions in both epiblast and extraembryonic cells to mediate signals that are required for egg cylinder organization and gastrulation.

Activin Receptors, Type I↗

Propionic acid production by extractive fermentation. I. Solvent considerations.

Solvent selection for extractive fermentation for propionic acid was conducted with three systems: Alamine 304-1 (trilaurylamine) in 2-octanol, 1-dodecanol, and Witcohol 85 NF (oleyl alcohol). Among them, the solvent containing 2-octanol exhibited the highest partition coefficient in acid extraction, but it was also toxic to propionibacteria. The most solvent-resistant strain among five strains of the microorganism was selected. Solvent toxicity was eliminated via two strategies: entrapment of dissolved toxic solvent in the culture growth medium with vegetable oils such as corn, olive, or soybean oils; or replacement of the toxic 2-octanol with nontoxic Witcohol 85 NF. The complete recovery of acids from the Alamine 304-1/Witcohol 85 NF was also realized with vacuum distillation.

Fermentation↗

Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer.

The identification of cell surface antigens is critical to the development of new diagnostic and therapeutic modalities for the management of prostate cancer. Prostate stem cell antigen (PSCA) is a prostate-specific gene with 30% homology to stem cell antigen 2, a member of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA encodes a 123-aa protein with an amino-terminal signal sequence, a carboxyl-terminal GPI-anchoring sequence, and multiple N-glycosylation sites. PSCA mRNA expression is prostate-specific in normal male tissues and is highly up-regulated in both androgen-dependent and -independent prostate cancer xenografts. In situ mRNA analysis localizes PSCA expression in normal prostate to the basal cell epithelium, the putative stem cell compartment of the prostate. There is moderate to strong PSCA expression in 111 of 126 (88%) prostate cancer specimens examined by in situ analysis, including high-grade prostatic intraepithelial neoplasia and androgen-dependent and androgen-independent tumors. Flow cytometric analysis demonstrates that PSCA is expressed predominantly on the cell surface and is anchored by a GPI linkage. Fluorescent in situ hybridization analysis localizes the PSCA gene to chromosome 8q24.2, a region of allelic gain in more than 80% of prostate cancers. A mouse homologue with 70% amino acid identity and similar genomic organization to human PSCA has also been identified. These results support PSCA as a target for prostate cancer diagnosis and therapy.

Amino Acid Sequence↗

Single nucleotide polymorphism hunting in cyberspace.

Large-scale sequencing of human cDNA and genomic DNA libraries has produced a large collection of sequence data in public databases. To date, >900,000 human expressed sequence tag (EST) sequences and >80,000,000 bases of genomic DNA sequence have been deposited in Genbank. This ever-expanding data set is a rich source of gene-associated and anonymous single nucleotide polymorphisms (SNPs). DNA sequence variations can be found by comparing the sequences of redundant ESTs and by comparing sequences from overlapping genomic clones. Initial studies have shown that, with proper computer screening, informative SNP markers can be developed from these DNA databases in an efficient and cost-effective manner. Complete public access to these databases will allow individual investigators to add biological value to the human sequence data generated by large-scale sequencing centers.

DNA↗

Overlapping genomic sequences: a treasure trove of single-nucleotide polymorphisms.

An efficient strategy to develop a dense set of single-nucleotide polymorphism (SNP) markers is to take advantage of the human genome sequencing effort currently under way. Our approach is based on the fact that bacterial artificial chromosomes (BACs) and P1-based artificial chromosomes (PACs) used in long-range sequencing projects come from diploid libraries. If the overlapping clones sequenced are from different lineages, one is comparing the sequences from 2 homologous chromosomes in the overlapping region. We have analyzed in detail every SNP identified while sequencing three sets of overlapping clones found on chromosome 5p15.2, 7q21-7q22, and 13q12-13q13. In the 200.6 kb of DNA sequence analyzed in these overlaps, 153 SNPs were identified. Computer analysis for repetitive elements and suitability for STS development yielded 44 STSs containing 68 SNPs for further study. All 68 SNPs were confirmed to be present in at least one of the three (Caucasian, African-American, Hispanic) populations studied. Furthermore, 42 of the SNPs tested (62%) were informative in at least one population, 32 (47%) were informative in two or more populations, and 23 (34%) were informative in all three populations. These results clearly indicate that developing SNP markers from overlapping genomic sequence is highly efficient and cost effective, requiring only the two simple steps of developing STSs around the known SNPs and characterizing them in the appropriate populations.

Bacteriophage P1↗