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Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 919 records · Page 51Linked to original sources
PubMed1998

Intrinsic controls of intracellular calcium and intercellular communication in the regulation of neuroendocrine cell activity.

1. The magnocellular hypothalamoneurohypophysial system, consisting chiefly of the supraoptic and paraventricular nuclei and their axonal projections to the pituitary neural lobe, has become a model for the study of neuroendocrine cell morphology, function, and plasticity. 2. Decades of research have produced a wealth of knowledge about the physiological conditions that activate this system, the peripheral target tissues affected by its outputs, and its capacity to undergo use-dependent, reversible reorganization. 3. Earlier research on the neural control of this system concentrated largely on the synaptic inputs that influence the activity of these magnocellular neurons and, while that task is still far from completed, methods have now been developed that permit insights to be gained into the control exercised by intrinsic cellular and molecular mechanisms. 4. This article reviews the current state of knowledge of roles played by these intrinsic mechanisms, including influences of intracellular calcium buffering, calcium release from internal stores and intercellular communication through gap junctions, in the control of neuroendocrine cell activity.

Animals↗
PubMed1998

A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy.

Desmin-related myopathies (DRM) are inherited neuromuscular disorders characterized by adult onset and delayed accumulation of aggregates of desmin, a protein belonging to the type III intermediate filament family, in the sarcoplasma of skeletal and cardiac muscles. In this paper, we have mapped the locus for DRM in a large French pedigree to a 26-cM interval in chromosome 11q21-23. This region contains the alphaB-crystallin gene (CRYAB), a candidate gene encoding a 20-kD protein that is abundant in lens and is also present in a number of non-ocular tissues, including cardiac and skeletal muscle. AlphaB-crystallin is a member of the small heat shock protein (shsp) family and possesses molecular chaperone activity. We identified an R120G missense mutation in CRYAB that co-segregates with the disease phenotype in this family. Muscle cell lines transfected with the mutant CRYAB cDNA showed intracellular aggregates that contain both desmin and alphaB-crystallin as observed in muscle fibers from DRM patients. These results are the first to identify a defect in a molecular chaperone as a cause for an inherited human muscle disorder.

Animals↗
PubMed1998

The effect of quality and amount of dietary fat on the susceptibility of low density lipoprotein to oxidation in subjects with impaired glucose tolerance.

OBJECTIVES: We examined the effects of a high fat diet rich in monounsaturated fat (MUFA-diet) and a moderate fat diet rich in polyunsaturated fat (PUFA-diet) on the susceptibility of LDL to oxidation. SUBJECTS: 29 subjects with impaired glucose tolerance. METHODS: After consuming a run-in diet [37% of energy (E%) fat, 18 E% saturated fat] for three weeks, subjects were randomly assigned either to a MUFA-diet (40 E% fat, 19 E% monounsaturated fatty acids) or a PUFA-diet (34 E% fat, 10 E% polyunsaturated fat) for eight weeks. The susceptibility of LDL to oxidation was measured by challenging LDL with hemin and H2O2 and measuring the time for the reaction to reach maximum velocity. Results are expressed as lag time to oxidation in minutes. RESULTS: In the PUFA-diet group (n = 15) lag time tended to decrease during the experimental diet (97 +/- 28 vs 90 +/- 25 min, mean +/- s.d., P = 0.073), whereas in the MUFA-diet group (n = 14) there was no significant change (lag time 96 +/- 24 vs 100 +/- 16 min, P = 0.408). The mean change in lag time was -7 +/- 14 min (-7.2%) in the PUFA-diet group and +4 +/- 16 min (+4.0%) in the MUFA-diet group (P = 0.029, PUFA-diet group vs MUFA-diet group). The alpha-tocopherol concentration in LDL increased significantly (P < 0.01) in both diet groups relative to the run-in diet period, but LDL particle score did not change in either of the diet groups during the dietary intervention. In subjects with impaired glucose tolerance a PUFA-rich diet with a moderate amount of fat tended to increase the susceptibility of LDL to oxidation as compared to a higher fat diet rich in MUFA. Furthermore, the negative mean change in lag time to oxidation found in the PUFA-diet group differed significantly from the slightly positive mean change found in the MUFA-diet group.

Cholesterol Esters↗
PubMed1998

Efficacy of multiple administrations of a recombinant adenovirus expressing wild-type p53 in an immune-competent mouse tumor model.

Infection of Renca cells in vitro with a recombinant adenovirus expressing a marker gene beta-galactosidase resulted in high level of the transgene expression. Renca tumors grown in Balb/C mice were also infectable with this recombinant adenovirus. The transgene expression in the tumors lasted for about 7 days, however, administration of another dose of Ad-beta gal, on day 7 produced beta-galactosidase expression. To investigate the effect of antibodies to adenovirus, animals were injected with multiple doses of adenovirus to produce neutralizing antibodies. To these animals Renca cells were injected and tumors formed. Interestingly, when Ad beta-gal was administered into these tumors, a high level of transgene expression was still observed. We next explored the utility of a recombinant adenovirus expressing p53 (AdWTp53) in the Renca tumor model. Renca cells when exposed to an adenovirus expressing p53 (AdWTp53) produced a high level of p53 protein, a p53-inducible gene p21/WAF1/Cip1 and underwent apoptosis. A single injection of AdWTp53 (10(9) plaque forming units) resulted in significant inhibition of tumor growth. However, multiple administrations (four doses of 2.5 x 10(8) plaque forming units) of AdWTp53 were needed for tumor cures. Mixing uninfected and AdWTp53-infected cells showed a bystander effect of AdWTp53-infected Renca cells. Based on these results we believe that an appropriate dose scheduling of AdWTp53 can be efficacious for cancer gene therapy in immune-competent tumor-bearing animals.

Adenoviridae↗
PubMed1998

Highly-efficient gene transfer with retroviral vectors into human T lymphocytes on fibronectin.

Genetically modified lymphocytes have been successfully used for correction of ADA deficiency in children and in controlling graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation. Low transduction efficiencies are, however, limiting for gene therapeutic strategies based on lymphocytes. In this study we compared protocols for highly efficient gene transfer into human T cells using retroviral vector-containing supernatant. We showed that infection of both human primary T cells and CD4+ Jurkat cells is most efficient on the matrix component fibronectin. Transduction was carried out with a retroviral vector encoding both the human intracytoplasmatically truncated low-affinity nerve growth factor receptor (deltaLNGFR) as a gene transfer marker and the Herpes simplex virus thymidine kinase for negative selection. Based on LNGFR expression genetically modified cells were enriched to near purity by magnetic cell sorting (MACS). Enriched cells could be shown to be highly sensitive to ganciclovir.

Anti-Allergic Agents↗
PubMed1998

Collagen biosynthesis by neointimal smooth muscle cells cultured from rabbit aortic explants 15 weeks after de-endothelialization.

Extracellular matrix (ECM) accumulation in arterial neointima, developed in response to de-endothelialization, is a prolonged process. In this study, we examined the relationship between increased collagen accumulation and synthetic activity of neointimal smooth muscle cells (SMCs) derived from aortic explants fifteen weeks after balloon catheter injury. Freshly confluent SMCs, derived either from normal aorta or from aortic neointima, were used in this study. The newly synthesized collagen was analysed by measuring [3H]-proline incorporation; and the mRNA expression for two major types of collagen, collagen type I and type III, was studied by Northern blot analysis. Our results indicated a three fold increase in protein (collagen) synthesis by neointimal SMCs. At the same time, the steady-state mRNA for procollagen I and procollagen III was elevated five and three times, respectively. These data indicate that persistent synthesis contributes to collagen accumulation in the arterial neointima and both transcriptional and post-transcriptional regulation take part in this process.

Animals↗
PubMed1998

Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs.

The molecular mechanisms associated with the pathogenesis of tuberculosis are not well understood. The present study evaluated the role of catalase-peroxidase as a potential virulence factor for Mycobacterium tuberculosis. Growth and persistence of M. tuberculosis H37Rv in intravenously infected BALB/ c mice were compared with katG-deleted, isoniazid-resistant M. tuberculosis H37RVINHR. Transformation of M. tuberculosis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes into M. tuberculosis H37RvINHR restored its catalase-peroxidase activities and the ability of the recombinants to persist in spleens of mice and guinea pigs. Transformation with the TBkatG gene with the codon 463 R-->L mutation also restored catalase-peroxidase activity and enhanced persistence. However, transformants with the codon 275 T-->P mutant expressed low levels of enzymatic activity and failed to persist in guinea pig spleen, although they did survive in mouse tissues. These results indicate that KatG contributes to the ability of M. tuberculosis to grow and survive within the infected host tissues.

Animals↗
PubMed1998

Stability study of LSD under various storage conditions.

A controlled study was undertaken to determine the stability of LSD in pooled urine samples. The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. LSD concentrations were measured quantitatively by the Abuscreen RIA and by HPLC using a fluorescence detection method. Good correlation was observed between the immunoassay and the fluorescent integrity of the LSD molecule. Thermostability studies were conducted in the dark with various containers. These studies demonstrated no significant loss in LSD concentration at 25 degrees C for up to 4 weeks. After 4 weeks of incubation, a 30% loss in LSD concentration at 37 degrees C and up to a 40% at 45 degrees C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. We also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA. This study demonstrates the importance of proper storage conditions of LSD in urine in order to insure proper analytical testing results over time.

Chlorides↗
PubMed1998

Varying dietary fat type of reduced-fat diets has little effect on the susceptibility of LDL to oxidative modification in moderately hypercholesterolemic subjects.

The effect of the fatty acid composition of reduced-fat diets on the in vitro oxidation of LDL was examined in 14 moderately hypercholesterolemic [low density lipoprotein (LDL) > 3.36 mmol/L] postmenopausal female and male subjects (age 44-78 y). Each subject consumed each of five reduced-fat diets [30 energy percent (E%) fat, 17 E% protein and 53 E% carbohydrate] enriched in beef tallow, canola oil, corn oil, olive oil or rice bran oil (20 E%) for 32-d periods. In vitro oxidation of LDL was assessed by incubating LDL with hemin and hydrogen peroxide, and measuring the time required for the reaction to reach maximum velocity (lag time). LDL lag times were 93.2 +/- 25.8, 95.9 +/- 26.4, 104.2 +/- 32.7, 108.0 +/- 26.6 and 113.1 +/- 24.0 min for corn oil, beef tallow, rice bran oil, canola oil and olive oil periods, respectively. When the data from all dietary phases were pooled, LDL alpha-tocopherol level (r = 0.30, P = 0.01) and plasma 18:1/18:2 ratio (r = 0.22, P = 0.08) were positively related to resistance of LDL to oxidation. Differences induced by the dietary perturbations in LDL content of beta-cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-carotene or beta-carotene, and LDL particle size were not related to resistance of LDL to oxidation. In conclusion, in middle-aged and elderly moderately hypercholesterolemic subjects, the consumption of reduced-fat diets enriched in animal fat or vegetable oils with a relatively wide range of fatty acid profiles did not alter the in vitro susceptibility of LDL to oxidation. The advantages of reducing the saturated fat content of the diet were reflected in lower total and LDL cholesterol levels.

Adult↗
PubMed1998

Endogenous nitric oxide influences arteriovenous anastomosis adrenergic tone in the conscious rabbit ear.

The role of nitric oxide (NO) in the control of arteriovenous anastomoses (AVAs) has not been studied in vivo in a thermoregulatory end organ. In this study, the effect of local inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME) on the microvasculature in the rabbit ear (n=12) was observed in vivo through a chronically implanted ear microvascular chamber. Ear cutaneous blood perfusion (CBP), total auricular arterial flow (TAF), and ear temperature were monitored simultaneously with the direct microvascular observations. Results revealed that intrafacial artery infusion of L-NAME produced significant vasoconstriction of arterioles, AVAs, and venules (p < 0.05). A decrease of ear blood perfusion also was demonstrated by changes of CBP, TAF, and surface temperature. The data provide evidence that basal generation of NO influences the vascular resistance in the thermoregulatory end organ. Moreover, endogenous NO production may be more important in regulating the AVA flow than is flow in other parts of the rabbit ear microvasculature. The effects of NO inhibition on ear microvasculature were not abolished by superior cervical ganglionectomy, indicating that NO production in the rabbit ear is not a neurally mediated mechanism. Further study with a short-term rabbit ear preparation showed that inhibition of NO production with L-NAME enhanced microvascular constrictive responses to extraluminal application of norepinephrine. NO thus appears to play a role of basal vasodilator in opposition to the basal adrenergic vasoconstrictor tone in the rabbit ear.

Animals↗
PubMed1998

PEI1, an embryo-specific zinc finger protein gene required for heart-stage embryo formation in Arabidopsis.

We used virtual subtraction, a new gene isolation strategy, to isolate several genes of interest that are expressed in Arabidopsis embryos. These genes have demonstrated biological properties or have the potential to be involved in important biological processes. One gene isolated by virtual subtraction is PEI. It encodes a protein containing a Cys3His zinc finger domain associated with a number of animal and fungal transcription factors. In situ hybridization results showed that PEI1 is expressed throughout the embryo from globular to late cotyledon stage. Transgenic Arabidopsis plants expressing a PEI1 antisense gene produced white seeds in which embryo development did not progress through heart stage. Aberrant embryos failed to form cotyledons, but the embryonic root appeared to be normal. Aberrant embryos did not turn green, and the expression of genes involved in photomorphogenesis was drastically attenuated. In culture, aberrant embryos did not form true leaves, but root formation was apparently normal. These results suggest that PEI1 is an embryo-specific transcription factor that plays an important role during Arabidopsis embryogenesis, functioning primarily in the apical domain of the embryo.

Amino Acid Sequence↗
PubMed1998

Characterizing output for the Varian enhanced dynamic wedge field.

The output factor for an enhanced dynamic wedge (EDW) field, like that for a dynamic wedge field, is a complex function of the field dimension in the wedge direction. The large change in output for different field sizes (varying more than 40% for a 60 degrees wedge angle) is due to rescaling of the golden segmented treatment table (GSTT), which specifies the cumulative monitor unit weighting as a function of moving jaw position. The rescaling of the GSTT results in increased output on the central axis with a decrease in the value of the final moving jaw position in the wedge plane. The output factor (in air or in water) on the central axis of an EDW field can be predicted to within 1% by multiplying the output factor (in air or in water) of an open field of the same size with the ratio of the normalized GSTT (NGSTT) value at 4.5 cm, which corresponds to a 10 cm x 10 cm square field, to the NGSTT value at the final moving jaw position for the EDW field. Once the NGSTT factor is separated from the output for EDW fields, the field-size-dependent wedge factor varies less than 1%. This approach allows a simple and accurate determination of the output factor for rectangular and asymmetric EDW fields. The equivalent square method for determining output for rectangular fields applies to EDW fields with the same precision as it does to open fields. The output for EDW fields strongly depends on the final moving jaw position. Every 5-mm change in the final moving jaw position causes 3.5-5.4% error in monitor unit calculation.

Calibration↗
PubMed1998

A quality assurance test tool for high dose-rate remote afterloading brachytherapy units.

A QA test tool is designed to quantitatively measure the HDR source positioning error, and to facilitate quick and dependable HDR timer linearity test and daily output constancy check. The test tool consists of two concentric disks. The lower disk has a cutout for inserting an HDR catheter, and the upper disk accepts a diode or miniature ionization chamber and can rotate relative to the lower disk. Ionization readings from the source (transferred to the center of the disks) are obtained at two rotational positions of the upper disk which houses the detector. The ratio of the readings is used to determine the source-positioning error of the HDR unit relative to the nominal source position by a simple triangulation principle. Experimental measurements confirm that the QA test tool is sensitive to approximately 0.2 mm variance in source positioning errors. In addition, the QA test tool is suitable for other common HDR QA tests such as the source travel step size test, the daily HDR unit output constancy check, and the timer linearity test. Its simple and robust design permits routine clinical use and provides a high confidence level in the accurate operation of HDR units.

Biophysical Phenomena↗
PubMed1998

Protein kinase C-mediated down-regulation of beta1-adrenergic receptor gene expression in rat C6 glioma cells.

In the current study, we investigated the mechanism by which protein kinase C (PKC) regulates the expression of beta1-adrenergic receptor (beta1AR) mRNA in rat C6 glioma cells. Exposure of the cells to 4beta-phorbol-12-myristate-13-acetate (PMA), an activator PKC, resulted in a down-regulation of both beta1AR binding sites and mRNA levels in a time- and concentration-dependent manner. This effect was not observed with phorbol esters that do not activate PKC and was blocked by bisindolylmaleimide, a specific PKC inhibitor. Activation of PKC did not reduce the half-life of beta1AR mRNA but significantly decreased the activity of the beta1AR promoter, as determined by reporter analysis. A putative response element, with partial homology to a consensus cAMP response element, was identified by mutation analysis of the promoter at positions -343 to -336, relative to the translational start site. Mutation of this putative regulatory element, referred to as a beta1AR-PKC response element, completely blocked the PKC-mediated down-regulation of beta1AR promoter activity. Gel mobility shift analysis detected two specific bands when C6 cell extracts were incubated with a labeled DNA probe containing the beta1AR-PKC response element sequence. Formation of one of these bands was inhibited by an oligonucleotide probe containing a consensus CRE and disrupted by an antibody for cAMP response element binding protein. Based on these studies, we propose that the PKC-induced down-regulation of beta1AR gene transcription in C6 cells is mediated in part by a cAMP response element binding protein-dependent mechanism acting on a novel response element.

Animals↗
PubMed1998

Alteration in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV in quinolone-resistant clinical isolates of Staphylococcus epidermidis.

We examined 22 clinical isolates of Staphylococcus epidermidis to analyze the association of alterations in GyrA and ParC with fluoroquinolone resistance. The simultaneous presence of GyrA and ParC alterations was associated with a high level of fluoroquinolone resistance in the clinical isolates of S. epidermidis.

4-Quinolones↗
PubMed1998

Gram-negative bacteria produce membrane vesicles which are capable of killing other bacteria.

Naturally produced membrane vesicles (MVs), isolated from 15 strains of gram-negative bacteria (Citrobacter, Enterobacter, Escherichia, Klebsiella, Morganella, Proteus, Salmonella, and Shigella strains), lysed many gram-positive (including Mycobacterium) and gram-negative cultures. Peptidoglycan zymograms suggested that MVs contained peptidoglycan hydrolases, and electron microscopy revealed that the murein sacculi were digested, confirming a previous modus operandi (J. L. Kadurugamuwa and T. J. Beveridge, J. Bacteriol. 174:2767-2774, 1996). MV-sensitive bacteria possessed A1alpha, A4alpha, A1gamma, A2alpha, and A4gamma peptidoglycan chemotypes, whereas A3alpha, A3beta, A3gamma, A4beta, B1alpha, and B1beta chemotypes were not affected. Pseudomonas aeruginosa PAO1 vesicles possessed the most lytic activity.

Antibiosis↗