Biomedical subjects

W Zhou

Publications and source records attributed to W Zhou.

At least 253 records · Page 14Linked to original sources

PubMed1998

[The design and clinical application of an apparatus for monitoring neuromuscular transmission function during operation under general anaesthesia].

This paper introduces a monitoring system of musle relaxant in action during the operation under general anaesthesia. The design of the monitor is based on measurement of acceleration. It consists of an acceleration transducer, a nerve stimulator and a microcomputer unit. The transducer can be fastened to the thumb, and the signal of the thumb movement in response to ulnar nerve stimulation is measured and registered in the computing unit. In clinical practice, it has been proved that this new apparatus can achieve reliable evaluation of nuromuscular transmission function and improve the quality of anesthesia in patients care during surgical operation.

Anesthesia, General↗

PubMed1998

Hemodynamics of ophthalmic artery and central retinal artery and correlation with other factors in patients with primary open angle glaucoma.

OBJECTIVE: To investigate the hemodynamics of ophthalmic artery (OA) and central retinal artery (CRA) in patients with primary open angle glaucoma(POAG) and analyse the correlation between hemodynamics of OA and CRA and other factors. METHODS: The hemodynamics of OA and CRA in normal persons (102 eyes) and glaucomatous patients (102 eyes) were measured by Colour Doppler Image (CDI). The linear correlation analysis was made between OA and CRA about each of the following parameters: the peak systolic flow velocity (Vmax), the end diastolic velocity (Vmin). The multiple stepwise regression analysis was taken to investigate the correlation between each of the following hemodynamics of OA and CRA: Vmax and Vmin in 74 eyes with POAG and each of the following related factors in hemorrheology: whole blood apparent viscosity at low, medium and high shear rate, plasma viscosity and hematocrit. The multiple linear regression was applied to investigate the correlation between each of the following hemodynamics of OA and CRA: Vmax and Vmin in 69 eyes with POAG and each of the following blood vessel filling time: the arm-retinal artery (A-AT) and retinal artery-venous (A-VT) of the fundus fluorescein angiography(FFA). RESULTS: The Vmax, Vmin and time-averaged maximum velocity (Vmean) of OA and CRA in patients with POAG were lower than those in normal persons, but the resistance index (RI) of OA and CRA was higher than those in normal. There was a positive correlation between OA and CRA in Vmin, but a negative correlation between Vmin of OA and plasma viscosity. The whole blood apparent viscosity at low shear rate was clodely related to Vmax and Vmin of CRA. Also there was a negative correlation between Vmax of CRA and A-AT of the FFA. CONCLUSION: There was abnormal hemodynamics, which is influenced by blood viscosity, of OA and CRA in patients with POAG. Abnormal hemodynamics can affect the blood supply to optic disc and retina in POAG.

Blood Flow Velocity↗

PubMed1998

[Investigation on the luminescence properties of Er ions in Er-doped sol-gel silica glasses].

Er-doped sol-gel silica glasses which have room temperature photoluminescence at 1.54 microm and doped concentration of 10(20)/cm(3) have been prepared. The examination results Indicated: (1) PL spectrum has largest intensity at the 0.5W% doped concentration; (2) the intensity of PL decreased 74%, when the temperature raised form 4K to 300K; (3) The Er ion and O ions formed complexes with coordinated numbers of 8 or 9.

English Abstract↗

PubMed1998

Identifying markers for pancreatic cancer by gene expression analysis.

To begin to identify new tumor markers, we recently performed a systematic study of gene expression in cancers of the colon and pancreas. Of the 45,000 genes identified, 183 were found to be expressed at significantly elevated levels in pancreatic cancer. One of the genes was tissue inhibitor of metalloproteinase type I (TIMP-1), which encodes a secreted protein. Analysis of TIMP-1 serum levels revealed significant increases in pancreatic cancer patients, but TIMP-1 by itself was inadequate as a serum marker for cancer. However, a combination of individually suboptimal markers (TIMP-1, CA19-9, and carcinoembryonic antigen) detected 60% of 85 patients with pancreatic cancers in a highly specific manner. These results suggest that a systematic analysis of gene expression can reveal novel serum markers and that individually suboptimal markers can be combined to yield higher sensitivity and specificity.

Biomarkers, Tumor↗

PubMed1997

Human telomerase contains evolutionarily conserved catalytic and structural subunits.

We have cloned and characterized a human gene encoding TP2 (telomerase-associated protein 2), a protein with similarity to reverse transcriptases and the catalytic telomerase subunits from Saccharomyces cerevisiae and Euplotes aediculatus. Indirect immunofluorescence revealed that TP2 was localized to the nucleus. Using antibodies to endogenous and epitope-tagged TP2, we found that TP2 was associated specifically with human telomerase activity and the recently identified telomerase-associated protein TP1. Mutation of conserved residues within the reverse transcriptase domain of TP2 severely reduced associated telomerase activity. These results suggest that telomerase is an evolutionarily conserved multisubunit complex composed of both structural and catalytic subunits.

Amino Acid Sequence↗

PubMed1997

Crystal structure of the bacteriochlorophyll a protein from Chlorobium tepidum.

The bacteriochlorophyll (BChl) a protein from Chlorobium tepidum, which participates in energy transfer in green photosynthetic bacteria, has been crystallized using the sitting drop method of vapor diffusion. X-ray diffraction data collected from these crystals indicate that the crystals belong to the cubic space group P4132 with cell dimensions of a=b=c=169.5 A. A native X-ray diffraction data set has been collected to a resolution of 2.2 A. The initial solution was determined by using the molecular replacement method using the structure of the previously solved BChl a protein from Prosthecochloris aestuarii. A unique rotation and translation solution was obtained for two monomers in the asymmetric unit giving a pseudo-body centered packing. After rebuilding and refinement the model yields an R factor of 19.0%, a free R-factor of 28.3%, and good geometry with root-mean-square deviations of 0.013 A and 2.1 degrees for the bond lengths and angles, respectively. The structure of the BChl a protein from C. tepidum consists of three identical subunits related by a 3-fold axis of crystallographic symmetry. In each subunit the polypeptide backbone forms large beta-sheets and encloses a central core of seven BChl a molecules. The distances between neighboring bacteriochlorin systems within a subunit range between 4 A to 11 A and that between two bacteriochlorins from different subunits is more than 20 A. The overall structure is comparable with that of P. aestuarii but significant differences are observed for the individual bacteriochlorophyll structures. The surface of the trimer has a hydrophobic region that is modeled as the complex being a peripheral membrane protein partially embedded in the membrane. A general model is presented for the membrane organization with two of the bacteriochlorophyll structures in the membrane and transferring energy to the reaction center complex. In this model these two bacteriochlorophyll structures serve a similar role to the cofactors of integral membrane light-harvesting complexes although the protein structure surrounding the cofactors is significantly different for the BChl a protein compared with the integral membrane complexes.

Bacterial Proteins↗

PubMed1997

Substrate-based inhibitors of the (S)-adenosyl-L-methionine:delta24(25)- to delta24(28)-sterol methyl transferase from Saccharomyces cerevisiae.

A series of 31 side-chain-modified analogs of cholesterol, zymosterol, lanosterol, and cycloartenol and the steroidal alkaloids solasodine and solanidine were studied as inhibitors of (S)-adenosyl-L-methionine:delta24(25)-sterol methyl transferase (SMT) enzyme activity from Saccharomyces cerevisiae. Two classes of sterol methylation inhibitors were tested: substrate analogs, including mechanism-based inhibitors, and transition state analogs. Several novel sterol methylation inhibitors that contained an aza, aziridine, or ammonium group in the sterol side chain were prepared and tested for the first time. The degree and kinetic pattern of methylation inhibition were found to be influenced by the position and nature of the variant functional group introduced into the side chain. The most potent inhibitors of SMT enzyme activity were transition state analog inhibitors (Ki values of 5 to 10 nM) that mimicked the structure and conformation of the natural substrate presumed to form in the ternary complex generated in the transition state. Steroidal alkaloids were potent competitive inhibitors with Ki values ranging from 2 to 30 microM, which is about the Kmapp of zymosterol, ca. 27 microM. An isosteric analog of the natural substrate, zymosterol, in which the 26/27-gem-dimethyl groups were joined to form a cyclopropylidene function is shown to be a potent irreversible mechanism-based inactivator of SMT enzyme activity that exhibits competitive-type inhibition, Ki 48 microM with a K(inact) of 1.52 min(-1). Mechanistic implications of these results provide new insights into the topology of the ternary complex involving sterol-AdoMet-enzyme.

Binding Sites↗

PubMed1997

Gene expression profiles in normal and cancer cells.

As a step toward understanding the complex differences between normal and cancer cells in humans, gene expression patterns were examined in gastrointestinal tumors. More than 300,000 transcripts derived from at least 45,000 different genes were analyzed. Although extensive similarity was noted between the expression profiles, more than 500 transcripts that were expressed at significantly different levels in normal and neoplastic cells were identified. These data provide insight into the extent of expression differences underlying malignancy and reveal genes that may prove useful as diagnostic or prognostic markers.

Colorectal Neoplasms↗

PubMed1997

Transgenic mice overexpressing human c-mpl ligand exhibit chronic thrombocytosis and display enhanced recovery from 5-fluorouracil or antiplatelet serum treatment.

The consequences of long-term in vivo expression of human c-mpl ligand in a mouse model were examined. Transgenic mice expressing the human full-length cDNA in the liver exhibited a fourfold increase in circulating platelet count that persisted stably over the life of the animals. Transgenic animals thrived and appeared healthy for at least 500 days. Transgenic platelets appeared normal with respect to surface antigens and response to platelet aggregation agonists. The highest-expressing transgenic line maintained human c-mpl ligand serum levels of 3 ng/mL. Megakaryocyte numbers in bone marrow and spleen were elevated, as were bone marrow and spleen megakaryocyte colony-forming cells (MEG-CFC). Megakaryocytes were observed in the bone marrow, spleen, liver, and lung, but in no other sites. Circulating myeloid and lymphoid cell populations were increased twofold. Additionally, the animals had a slight but significant anemia despite an increase in marrow colony-forming units-erythroid (CFU-E). No evidence of myelofibrosis was observed in the bone marrow. The platelet nadir in response to administration of either antiplatelet serum (APS) or 5-fluorouracil (5FU) was significantly reduced relative to the control level. Furthermore, the red blood cell (RBC) nadir was reduced relative to control levels in both models, suggesting that c-mpl ligand can directly or indirectly support the maintenance of erythrocyte levels following thrombopoietic insult.

Animals↗

PubMed1997

A mammalian telomerase-associated protein.

The telomerase ribonucleoprotein catalyzes the addition of new telomeres onto chromosome ends. A gene encoding a mammalian telomerase homolog called TP1 (telomerase-associated protein 1) was identified and cloned. TP1 exhibited extensive amino acid similarity to the Tetrahymena telomerase protein p80 and was shown to interact specifically with mammalian telomerase RNA. Antiserum to TP1 immunoprecipitated telomerase activity from cell extracts, suggesting that TP1 is associated with telomerase in vivo. The identification of TP1 suggests that telomerase-associated proteins are conserved from ciliates to humans.

Amino Acid Sequence↗

PubMed1997

Characterization of the yeast transcriptome.

We have analyzed the set of genes expressed from the yeast genome, herein called the transcriptome, using serial analysis of gene expression. Analysis of 60,633 transcripts revealed 4,665 genes, with expression levels ranging from 0.3 to over 200 transcripts per cell. Of these genes, 1981 had known functions, while 2684 were previously uncharacterized. The integration of positional information with gene expression data allowed for the generation of chromosomal expression maps identifying physical regions of transcriptional activity and identified genes that had not been predicted by sequence information alone. These studies provide insight into global patterns of gene expression in yeast and demonstrate the feasibility of genome-wide expression studies in eukaryotes.

Cell Cycle↗

PubMed1997

Antifungal sterol biosynthesis inhibitors.

During the course of the last decade, the development of SBIs, and particularly sterol biomethylation inhibitors, has been based on the rational design approach. Successful though this approach has been in elucidating sterol biomethylation enzymology, its limitations are becoming apparent from the findings that: (i) 24,25-double bond metabolism gives rise to cholesterol and ergosterol in a mechanistically similar manner, (ii) 25-azasterols are harmful to human physiology, and (iii) side-chain modified sterols designed to inhibit the SMT enzyme in S. cerevisiae may be ineffective or operate by another kinetic mechanism in a related organism, rendering it therapeutically nonuseful. Nevertheless, it may be possible to ultimately capitalize on the unique aspects of sterol biomethylation chemistry and enzymology to design taxa-specific inhibitors. With increased understanding of the structure and function of SMT enzymes in different fungi, it should be possible to prepare novel mechanism-based inactivators to control SMT activity uniquely and with high specific activity.

Amino Acid Sequence↗

PubMed1997

Binocular eye movements not coordinated during REM sleep.

Rapid eye movements (REMs) are a defining characteristic of REM sleep during which vivid dreams occur. It has been suggested that REMs may be binocularly coordinated and related to "watching" dream images. For the first time, binocular eye movements were recorded during natural REM sleep in monkeys to test the conjugate nature of the oculomotor system and the "scanning hypothesis" of REMs during sleep. During REM sleep, the lines of sight of the two eyes are frequently misaligned up to 30 degrees horizontally and/or vertically. Since the lines of sight usually don't intersect, there is no fixation point. Instead, each eye is aimed at a different part of the visual field during REM sleep. Furthermore, REMs are not usually conjugate, but are disjunctive or even monocular in horizontal or vertical directions. These data argue against the idea that REMs actually "track" dream images, unless each eye is watching its own dream! Binocular misalignment and disjunctive (even monocular) REMs during sleep suggest that separate left eye and right eye pathways generate saccades in each eye and control the position of each eye. Binocular coordination cannot be the passive result of anatomical connectivity as has been argued previously, but instead must result from a high-level process associated with the awake state that coordinates activity in left-eye and right-eye pathways. Hering's law of equal innervation is not consistent with these data.

Animals↗

PubMed1997

Sterol utilization and metabolism by Heliothis zea.

Heliothis zea (corn earworm), an insect that fails to synthesize sterols de novo, was reared on an artificial diet treated with 18 different sterol supplements. Larvae did not develop on a sterol-less medium. delta 5-Sterols with a hydrogen atom, a methylene group, an E- or Z-ethylidene group, or an alpha- or beta-ethyl group (cholesterol, ostreasterol, isofucosterol, fucosterol, sitosterol, and clionasterol, respectively) at position C-24, and delta 5-sterols doubly substituted in the side chain at C-24 with an alpha-ethyl group and at C-22 with a double bond (stigmasterol) supported normal larval growth to late-sixth instar (prepupal: maturity). The major sterol isolated from each of these sterol treatments was cholesterol, suggesting that H. zea operates a typical 24-dealkylation pathway. The sterol requirement of H. zea could not be met satisfactorily by derivatives of 3 beta-cholestanol with a 9 beta, 19-cyclopropyl group, gem dimethyl group at C-4, a delta 5,7-bond or delta 8-bond, or by side chain modified sterols that possessed a delta 25(27)-24 beta-ethyl group, delta 23(24)-24-methyl group or 24-ethyl group, or delta 24(25)-24-methyl or 24-ethyl group. The major sterol recovered from the larvae (albeit developmentally arrested larvae) treated with a nonutilizable sterol was the test compound. Sterol absorption was related to the degree of sterol utilization. The most effective sterols absorbed by the insect ranged from 27 to 66 micrograms per insect, whereas the least effective sterols absorbed by the insect ranged from 0.6 to 6 micrograms per insect. Competition experiments using different proportions of cholesterol and 24-dihydrolanosterol (from 9:1 to 1:9 mixtures) indicated that abnormal development of H. zea may be induced on less than a 1 to 1 mixture of utilizable (cholesterol) to nonutilizable (24-dihydrolanosterol) sterols. The results demonstrate new structural requirements for sterol utilization and metabolism by insects, particularly with respect to the position of double bonds in the side chain and functionalization in the nucleus. The novel sterol specificities observed in this study appear to be associated with the dual role of sterols as membrane inserts (nonmetabolic) and as precursors to the ecdysteroids (metabolic).

Animals↗

PubMed1997

Photosensitizing activity of the anti-bacterial drugs sulfamethoxazole and trimethoprim.

The photochemical reactions in vitro of sulfamethoxazole alone and in combination with trimethoprim were studied to obtain information on the photosensitization mechanism. Sulfamethoxazole in aqueous solution, on exposure to UVB radiation, generates free radicals and singlet oxygen, with the neutral molecule being at least twice as active as the sulfamethoxazole anion. Photoexcited sulfamethoxazole can participate in electron transfer to cytochrome-c and nitro blue tetrazolium, and sensitizes the peroxidation of linoleic acid and the hemolysis of human erythrocytes, predominantly by a free radical mechanism. Trimethoprim is relatively inactive in the same photochemical systems.

Anti-Infective Agents↗

PubMed1997

TNF-alpha regulation of C3 gene expression and protein biosynthesis in rat glomerular endothelial cells.

Glomerular endothelial cells are an important site of interaction with the cellular and soluble components of inflammation. To investigate the capacity of these cells to synthesize complement they were cloned from isolated rat glomeruli. Messenger RNA (mRNA) was extracted from the cells, reverse transcribed and used as the template to identify specific gene transcripts with the polymerase chain reaction (PCR). mRNA coding for the third component of the complement cascade (C3) was detected in unstimulated endothelial cells, whereas no message for the fourth component (C4) could be demonstrated. Using a semiquantitative method of PCR, we found that the expression of C3 is up-regulated by the cytokine tumor necrosis factor-alpha (TNF-alpha), but not by the cytokines interferon-gamma (IFN-gamma) and interleukin 1 alpha (IL-1 alpha). The increase in levels of C3 mRNA occurred in a time and dose dependent manner. This increase was dependent on new protein synthesis. Production of the C3 protein was demonstrated by radiolabeling and immunoprecipitation, and this also was stimulated by TNF-alpha. In conclusion, we demonstrate the production of C3 by microvascular endothelium of glomerular origin and its stimulation by TNF-alpha. We believe that this local synthesis could have a role in the pathogenesis of disease, however, the nature of this role at present remains unclear.

Animals↗

PubMed1997

Mutagenicity of scooter exhaust particulate matter.

By using the in vitro Ames Salmonella/microsomal assay and the in vivo mouse micronucleus assay, studies were performed to evaluate the genotoxicity of gasoline exhaust particulate matter generated from five different domestic and imported scooters. In the Ames assay, treatment of test strains TA98 and TA100 with solvent extracts of particulate matter from four of five scooter models caused an increase in the number of histidine-independent colonies over the background in TA98 without S9 mix. Positive results were also obtained from the micronucleus assay. The frequencies of bone marrow micronucleated polychromatic erythrocytes were significantly higher in the treated compared to the nontreated animals, and the increases in the frequencies were not significantly different among the five types of scooters. Analyses of chemical components showed that scooter exhaust particulate matter contained more than 100 different substances including polycyclic aromatic hydrocarbons.

Air Pollutants↗

PubMed1997

Modulation of cardiac calcium channels by propofol.

BACKGROUND: Propofol elicits a rapid depression of transsarcolemmal Ca2+ influx and myocardial contractility. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that propofol acts as an antagonist of L-type calcium channels. METHODS: Experiments monitored effects of propofol on (1) the binding of [3H]nitrendipine (a 1,4-dihydropyridine calcium channel antagonist) to rat myocardial membranes; (2) L-type calcium current (ICa,L) as determined using whole-cell patch-clamp techniques in intact rat cardiomyocytes; and (3) myocardial contractility as examined in isolated rat papillary muscle. RESULTS: Propofol, in concentrations as low as 6 microM, increased the apparent dissociation constant (Kd) for [3H]nitrendipine without affecting binding-site density (Bmax). This decrease in dihydropyridine-binding affinity was associated with a depressed ICa,L in cardiomyocytes and diminished myocardial contractility. Other experiments showed that etomidate has no effect on [3H]nitrendipine binding, whereas ketamine enhances dihydropyridine binding. CONCLUSION: Results suggest that propofol may inhibit cardiac L-type calcium current by interacting with the dihydropyridine-binding site.

Animals↗