Search PubMed⌕ Search

Biomedical subjects

J Zhu

Publications and source records attributed to J Zhu.

At least 757 records · Page 42Linked to original sources

Identification and characterization of a complex chromosomal replication origin in Schizosaccharomyces pombe.

In the budding yeast, S. cerevisiae, two-dimensional (2D) gel electrophoresis techniques permit mapping of DNA replication origins to short stretches of DNA (+/- 300 bp). In contrast, in mammalian cells and Drosophila, 2D gel techniques do not permit precise origin localization; the results have been interpreted to suggest that replication initiates in broad zones (several kbp or more). However, alternative techniques (replication timing, nascent strand polarity analysis, nascent strand size analysis) suggest that mammalian origins can be mapped to short DNA stretches, just like S. cerevisiae origins. Because the fission yeast, Schizosaccharomyces pombe, resembles higher organisms in several ways to a greater extent than does S. cerevisiae, we thought that S. pombe replication origins might prove to resemble--and thus be helpful models for--animal cell origins. An attempt to test this possibility using 2D gel techniques resulted in identification of a replication origin near the ura4 gene on chromosome III of S. pombe. The 2D gel patterns produced by this S. pombe origin indeed resemble the patterns produced by animal cell origins and show that the S. pombe origin cannot be precisely located. The data suggest an initiation zone of 3-5 kbp. Some aspects of the 2D gel patterns detected at the S. pombe origin cannot be explained by the rationale of initiation in broad zones, suggesting that future biochemical and genetic studies of this complex origin are likely to provide information useful in helping to understand the apparent conflict between the 2D gel mapping techniques and other mapping techniques at animal cell origins.

Chromosomes, Fungal↗

Light-dark variations in ocular timolol concentrations following topical solution instillation in the pigmented rabbit.

The objective of this study was to determine whether ocular absorption of topically applied timolol in the pigmented rabbit varied with the time of drop instillation. Twenty-five microliters of a 0.65% timolol maleate solution were instilled in the pigmented rabbit eye at 0600, 0900, 1200, 1500, 1800, 2100, 2400, or 0300 hr. Timolol concentrations in the conjunctiva, sclera, corneal epithelium, corneal stroma, aqueous humor, and iris-ciliary body at 15 and 30 min post-dosing were monitored using reversed phase HPLC. Ocular timolol concentrations were higher when the drug was administered during the light period (0900-1800 hr) than when it was administered during the dark period (1800-0600 hr). There exist, therefore, light-dark variations in the ocular absorption of topically applied timolol.

Absorption↗

Tannic acid intoxication in sheep and mice.

Acute tannic acid intoxication was studied in mice and sheep. In mice, following oral administration of 2.0 to 4.6 g of tannic acid kg-1 bodyweight, periacinar coagulative and haemorrhagic necrosis occurred in the liver. In sheep, following oral (8 g kg-1 bodyweight) administration of tannic acid, liver necrosis was not observed either histologically or detected biochemically, although transmission electron microscopy showed focal hepatocellular necrosis, steatosis and acicular crystal cleft formation. In sheep given tannic acid intraperitoneally (0.1 g kg-1 bodyweight), liver necrosis occurred and plasma sodium and glucose levels significantly (P < 0.05) decreased while packed cell volume and plasma aspartate aminotransferase, alkaline phosphatase, creatinine and bilirubin significantly (P < 0.01) rose. The results for blood-gas and acid-base determinations, blood haemoglobin and oxygenation showed significant increases in arterial blood methaemoglobin concentration (P < 0.05) and decreases in blood pH (P < 0.01) and oxyhaemoglobin concentration (P < 0.05) in sheep by 32 hours after oral dosing with 8 g of tannic acid kg-1 bodyweight. In sheep given tannic acid intraperitoneally, methaemoglobinaemia was not detected, but metabolic acidosis with a compensatory respiratory alkalosis occurred. Thus, it would appear that although tannic acid is hepatotoxic when given orally to mice or intraperitoneally to sheep, it does not produce renal or significant hepatic injury in sheep when given orally, but rather causes metabolic acidosis and methaemoglobinaemia.

Administration, Oral↗

Effects of zimeldine and its metabolites, clomipramine, imipramine and maprotiline in experimental allergic neuritis in Lewis rats.

The influence of the selective serotonin (5-HT) reuptake inhibiting antidepressant zimeldine and its metabolite norzimeldine was tested on experimental allergic neuritis (EAN) in Lewis rats, which is an animal model of the Guillain-Barré syndrome (GBS) in man. Zimeldine and norzimeldine both suppressed clinical signs of actively induced EAN when given at a dose of 20 mg/kg/day intraperitoneally via osmotic pumps. The effects of zimeldine, its metabolites norzimeldine and CPP 200 as well as of the antidepressants clomipramine, imipramine and maprotiline on in vitro immune response were tested. Thereby we used an immunospot assay for interferon-gamma (IFN-gamma) produced by lymph node mononuclear cells (MNC), which reflects number of memory T lymphocytes activated by antigen or lectin, in this experiment bovine peripheral nerve myelin (BPM) and phytohemagglutinin (PHA), respectively. In the IFN-gamma secretion assay zimeldine, CPP 200, clomipramine and maprotiline all in a concentration-dependent mode reduced the number of IFN-gamma secreting cells while norzimeldine and imipramine did not affect the IFN-gamma secretion. In assays for proliferation in response to antigen or lectin, the concentration 10(-4) M was judged toxic for all substances tested, and at concentrations below that all but zimeldine showed a dose-dependent slight reduction of MNC proliferation. The action of several drugs on induced T cell secretion of IFN-gamma suggests that the mechanisms for the suppressive effect of zimeldine and norzimeldine on EAN symptoms can be due to an action on myelin T cell autoreactivity. All the monoamine reuptake inhibiting antidepressants tested in this study showed immunomodulatory effects by either a reduction of the number of IFN-gamma-secreting cells or the MNC proliferation. These observations call for further studies of immunological mechanisms in the pathogenesis of mental disorders as well as on the potential role of drugs acting on the monoamine systems in the treatment of recognized autoimmune diseases.

Animals↗

Characterization of cocaine-sensitive dopamine uptake in PC12 cells.

Dopamine uptake in rat pheochromocytoma (PC12) cells is a carrier-mediated process which follows Michaelis-Menten kinetics. Uptake was saturable with an apparent Km of 0.71 microM for dopamine and a Vmax of 3.2 pmol/2 x 10(5) cells/min. The rank order of potency for various amines was norepinephrine > or = dopamine > epinephrine. Uptake increased with increasing temperature and showed a sharp break in the Arrhenius plot at 27.5 degrees C. The Q10 was 1.39 above and 2.95 below 27.5 degrees C. Cocaine inhibited uptake in a dose-dependent manner with a Ki of 0.97 microM. The presence of cocaine lowered the apparent Km but did not affect the Vmax, indicating competitive inhibition. Tunicamycin inhibited [3H]dopamine accumulation in a dose- and time-dependent fashion suggesting the dopamine uptake site in PC12 cells is an asparagine-linked glycoprotein. Kinetic analysis showed a decrease in Vmax but not in the apparent Km after tunicamycin treatment, consistent with the notion that tunicamycin treatment results in the loss of a substantial amount of active carrier molecules.

Animals↗

Age estimation from the structure of adult human teeth: review of the literature.

The literature on age estimation from the structure of adult human teeth is reviewed. Several anatomic changes of teeth have been shown to be valuable in age determination, but there is still controversy concerning the accuracy of cemental annulation. It is believed that improvements in age estimation can be made using direct measurement rather than scoring systems.

Age Determination by Teeth↗

Sequential quantitative scintigraphy of parotid glands with chronic inflammatory diseases.

A practical, time-saving procedure for sequential quantitative scintigraphy is introduced and 4 parameters chosen from 12 parameters by discriminant analysis are used to evaluate the function of the parotid gland. The examination was performed in 120 cases, including 16 cases with recurrent parotitis in childhood, 33 with chronic obstructive parotitis (COP), 37 with Sjögren's syndrome (SS), 4 with sialadenosis, and 30 normal controls. The scintigraphic findings were analyzed and compared with the histologic findings. The diagnostic value of this method was investigated and scaling for differential diagnosis of COP and SS was established. Scintigraphy is considered to be a useful method for evaluation of parotid function and as a diagnostic aid for SS and COP, especially in patients in whom sialography cannot be performed.

Adolescent↗

Transformation of a continuous rat embryo fibroblast cell line requires three separate domains of simian virus 40 large T antigen.

Mouse C3H 10T1/2 cells and the established rat embryo fibroblast cell line REF-52 are two cell lines widely used in studies of viral transformation. Studies have shown that transformation of 10T1/2 cells requires only the amino-terminal 121 amino acids of simian virus 40 (SV40) large T antigen, while transformation of REF-52 cells requires considerably more of large T antigen, extending from near the N terminus to beyond residue 600. The ability of a large set of linker insertion, small deletion, and point mutants of SV40 T antigen to transform these two cell lines and to bind p105Rb was determined. Transformation of 10T1/2 cells was greatly reduced by mutations within the first exon of the gene for large T antigen but was only modestly affected by mutations affecting the p105Rb binding site or the p53 binding region. All mutants defective for transformation of 10T1/2 cells were also defective for transformation of REF-52 cells. In addition, mutants whose T antigens had alterations in the Rb binding site showed a substantial reduction in transformation of REF-52 cells, and the degree of this reduction could be correlated with the ability of the mutant T antigens to bind p105Rb. There was a tight correlation between the ability of mutants to transform REF-52 cells and the ability of their T antigens to bind p53. These results demonstrate that multiple regions of large T antigen are required for full transformation by SV40.

Animals↗

Mechanisms of interference with simian virus 40 (SV40) DNA replication by trans-dominant mutants of SV40 large T antigen.

Mutations at multiple sites within the simian virus 40 (SV40) early region yield large T antigens which interfere trans dominantly with the replicative activities of wild-type T antigen. A series of experiments were conducted to study possible mechanisms of interference with SV40 DNA replication caused by these mutant T antigens. First, the levels of wild-type T antigen expression in cells cotransfected with wild-type and mutant SV40 DNAs were examined; approximately equal levels of wild-type T antigen were seen, regardless of whether the cotransfected mutant was trans dominant or not. Second, double mutants that contained the mutation of inA2827, a strong trans-dominant mutation with a 12-bp linker inserted at the position encoding amino acid 520, and various mutations in other parts of the large-T-antigen coding region were constructed. The trans-dominant interference of inA2827 was not affected by second mutations within the p105Rb binding site or the amino or carboxy terminus of large T antigen. Mutation of the nuclear localization signal partially reduced the trans dominance of inA2827. The large T antigen of mutant inA2815 contains an insertion of 4 amino acids at position 168 of large T; this T antigen fails to bind SV40 DNA but is not trans dominant for DNA replication. The double mutant containing the mutations of both inA2815 and in A2827 was not trans dominant. The large T antigen of dlA2433 lacks amino acids 587 to 589, was unstable, and failed to bind p53. Combining the dlA2433 mutation with the inA2827 mutation also reversed the trans dominance completely, but the effect of the dlA2433 mutation on trans dominance can be explained by the instability of this double mutant protein. In addition, we examined several mutants with conservative point mutations in the DNA binding domain and found that most of them were not trans dominant. The implications of the results of these experiments on possible mechanisms of trans dominance are discussed.

3T3 Cells↗

Localization of a DNA replication origin and termination zone on chromosome III of Saccharomyces cerevisiae.

Two-dimensional gel electrophoretic replicon mapping techniques were used to identify all functional DNA replication origins and termini in a 26.5-kbp stretch in the left arm of yeast chromosome III. Only one origin was detected; it coincided with an ARS element (ARS306), as have all previously mapped yeast origins. A replication termination region was identified in a 4.3-kbp stretch at the telomere-proximal end of the investigated region, between the origin identified in this paper and the neighboring, previously mapped, ARS305-associated origin (previously called the A6C origin). Termination does not occur at a specific site; instead, it appears to be the consequence of replication forks converging in a stretch of DNA of at least 4.3 kbp.

Chromosomes, Fungal↗

[Analysis of active ingredients in wuren liguid].

The active ingredients and their relative concentration in Wuren liquid were analyzed by GC/MS. It has been found that there are concentrative antimicrobiological ingredients in the liquid such as phenols, benzoic acids, fatty acids, and so on. The results have confirmed the effectiveness of Wuren liquid in disinfection, germ-killing and treatment of skin diseases.

Anti-Infective Agents↗

[Effects of platelet activating factor on the cerebrovascular permeability in rats and the protection by drug].

The action of platelet activating factor in the rat brain was detected by Evans blue staining after injection of PAF into the rat brain. The results show that PAF increased the Evans blue staining of the brain, but no staining was observed without prior injection of PAF. Meanwhile, PAF was shown to stimulate the release of 14C-arachidonic acid (14C-AA) in the cerebral microvascular smooth muscle cells (CMSMC). SZ-1, a new synthetic drug, dose-dependently inhibited the Evans blue staining of the rat brain and the PAF induced 14C-AA release in CMSMC. These results indicate that the action of PAF in the rat brain might be related to the stimulation of AA release. SZ-1 may antagonize the PAF receptor and protect the brain from PAF induced damage.

Animals↗

Specific binding sites of platelet activating factor on the intact bovine cerebral microvascular endothelial cells and antagonism of drugs.

[3H]Triazolodiazepine ([3H]WEB 2086), an antagonist of platelet activating factor (PAF) receptor, was studied as radioligand on intact cerebral microvascular endothelial cells (CMEC). The results showed that the binding of [3H]triazolodiazepine reached and maintained at an equilibrium after 15-120 min of incubation and that it was saturable with increasing concentration of radioligand. Scatchard analysis indicated that there were 2 specific binding sites on CMEC, its Kd1, Bmax1, Kd2, and Bmax2 were 3.13 nmol.L-1, 1.50 pmol/3 x 10(5) cells, 83.96 nmol.L-1, and 12.96 pmol/3 x 10(5) cells, respectively. The binding of [3H]triazolodiazepine to CMEC was displaced by C16-PAF and 1,5-bis-(3,4-dimethoxyphenyl)-tetrahydro-(4H)-pyran (SZ-1), which IC50 were 0.43 nmol.L-1 and 0.125 mumol.L-1, respectively. These data suggested the existence of PAF specific binding sites on CMEC.

Animals↗

Neuropeptide Y inhibits forskolin-stimulated adenylate cyclase in bovine adrenal chromaffin cells via a pertussis toxin-sensitive process.

The effect of neuropeptide Y (NPY) on adenylate cyclase activity and the role of G-proteins mediating NPY's effect were investigated in cultured bovine adrenal chromaffin cells. The equilibrium binding of [125I]NPY to sucrose gradient purified bovine adrenal medulla plasma membranes revealed high- (GTP gamma S sensitive) and low-affinity binding sites with calculated IC50 values of 0.27 nM and 0.14 microM, respectively. Inhibition of forskolin-stimulated cyclic AMP accumulation was dependent upon the NPY concentration (IC50 = 0.9 nM) and independent of cyclic AMP (cAMP) phosphodiesterase activity. NPY-related peptides, except peptide YY, and NPY fragments exhibited minimal inhibitory activity. The inhibitory effect of NPY on forskolin-stimulated adenylate cyclase activity was completely abolished by pretreatment of the cells with pertussis toxin (PTX). Incubation of membranes with PTX and [32P]nicotinamide adenine dinucleotide revealed a protein band with an apparent molecular mass of 41 kDa. The time course and dose dependence of PTX pretreatment for in vitro ADP-ribosylation were similar to those for PTX to attenuate the NPY effect on forskolin-stimulated adenylate cyclase activity. The direct relation between the NPY receptor and the PTX-sensitive G-protein was further shown by the ability of NPY to inhibit PTX-catalyzed in vitro ADP-ribosylation. ADP-ribosylation of the 41-kDa protein was partially inhibited by 5'-guanylylimidodiphosphate and further inhibited by high concentrations of NPY. An antibody against Gi1/i2 alpha 1 recognized two species of which a 41-kDa protein comigrated with the PTX substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗

[A 12-year clinical experience of cardiac valve replacement with domestic tilting disc valve prostheses in 1013 cases].

1013 patients with cardiac valve replacement during a 12-year period from 1978 to 1990 were reported. 566 cases were implanted with Shanghai-made tilting disc valve prostheses and 447 with Lanzhou-made (C-L valves). Mitral valve replacement (MVR) in 753 patients, aortic valve replacement (AVR) in 102 and double valves replacement (DVR) in 158. The overall early mortality rate was 6.2% with 4.9%, 7.8% and 11.3% after MVR, AVR and DVR respectively. Follow-up study was made in 3097.43 patient-year (mean 3.26 years). The late death rate was 1.6% patient-years and with 1.4, 1.8 and 3.2 after MVR, AVR and DVR respectively. The incidence of late valve-related complication (% patient-years) were: thromboembolism 0.39, anticoagulant-related hemorrhages 0.77, prostheses failure 0.22, prosthetic valve endocarditis 0.38, periprosthetic leak 0.12, and reoperations 0.38. The domestic tilting disc valve prostheses are considered to be qualified valves with low mortality and satisfactory results.

Adolescent↗