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Biomedical subjects

Z Lin

Publications and source records attributed to Z Lin.

At least 145 records · Page 8Linked to original sources
PubMed2000

Effect of kanglemycin C on lymphokin a production and gene expression of mouse splenocyte and macrophage.

AIM: To study the effect of kanglemycin C (KC) on production and gene transcription of lymphokins. METHODS: Cell proliferation and lymphokin activities were quantified with MTT colorimetry and ELISA, and gene transcriptions of lymphokins semi-quantified with RT-PCR. RESULTS: Suppression of KC on proliferation of enriched T-and B-cell respectively mediated by Con A and LPS was declined by addition of exogenous IL-1, IL-2, and IL-6. KC 80 nmol/L markedly inhibited IL-2 and IL-6 production and mRNA transcription of incubated mouse splenocytes induced by Con A. Additionally, KC had some suppression on IL-1beta and IL-6 productions of peritoneal macrophage stimulated by LPS (5microg/mL), whereas cyclosporine (CS) had not. CONCLUSION: Immunosuppression of KC came true partially through the decrease of IL-1beta, -2 and -6 productions, especially of IL-2. However, CS's immunosuppression was mainly through the decrease of IL-2 production.

Animals↗
PubMed2000

[Study on the aggregation state of sulfonated phthalimidomethyl zinc phthalocyanine in CEL solution].

Sulfonated Phthalimidomethyl Zinc Phthalocyanine is a new photodynamic therapy reagent, it can be selectively attacked to cell, but how it attacks the target cell is still unknowable. The aggregation state of photosensitizer is significant to its mechanism proved in CEL solution. The aggregation of ZnPcS2P2 in CEL has been studied with absorption spectroscopy and fluorescence spectroscopy. The aggregation state is dimer through theory analysis, monomer molar absorption coefficient as well as equilibrium constant were estimated.

Antineoplastic Agents↗
PubMed2000

[Simultaneous determination of mixed phenol, catechol, and quinol by double Fourier transform filtering and second ratio spectra derivative spectrophotometry].

A new spectrophotometric method for the simultaneous determination of three compounds in the same sample is proposed. The method is based on the combination of double Fourier transform filtering with second ratio spectra derivative. Each absorption spectrum is filtered twice using the bigger filter window than in the filtering once. The ratio spectrum is obtained by dividing the amplitudes of the absorption spectrum of the mixture by a standard spectrum of one of the components and getting the first derivative of the ratio spectrum of the two compounds. Then the derivative is divided by the corresponding first derivative of one of the two compounds and the second derivative is obtained. The second derivative at certain wavelength is proportional only to the concentration of one compound. The effect of double Fourier transform filtering and the optimization of experimental parameters have been studied. The method has been applied to the simultaneous determination of 0.01009-0.05325 mg.mL-1 phenol, catechol and quinol in a solution. The relative errors are between 0.07% and 5.4%.

Catechols↗
PubMed2000

[The synthesis and spectral study of multicomponent heteropoly compounds with Keggin structure].

The Multicomponent heteropoly compounds [Me4N]3 + x[PVxMoyW12-x-yO40]. n(H2O) with Keggin structure have been synthesized, and have been characterized by FTIR and NIR FT-Raman. The vibrational regularity of oxygen-containing bonds (P-Oa, M = Od, M-Ob-M and M-Oc-M) in these heteropoly compounds have been studied. The vibrational frequencies nu as (M = Od) and nu as (M-Ob-M) was shown to prove the reason why the acidity of the heteropoly compounds descended and the oxidization increased by the substitution of V atoms.

English Abstract↗
PubMed1999

ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells.

Ischemia induces apoptosis as well as necrosis of cardiac myocytes. We recently reported the cloning of a cDNA that encodes an apoptotic inhibitor, ARC, that is expressed predominantly in cardiac and skeletal muscle. In the present study, we examined the ability of ARC to protect rat embryonic heart-derived H9c2 cells from apoptosis induced by hypoxia, a component of ischemia. We found that H9c2 cells express ARC and that exposure to hypoxia substantially reduces ARC expression while inducing apoptosis. Transfected H9c2 cells in which cytosolic ARC protein levels remain elevated during hypoxia were significantly more resistant to hypoxia-induced apoptosis than parental H9c2 cells or H9c2 cells transfected with a control vector. Loss of endogenous ARC in the cytosol of H9c2 cells was associated with translocation of ARC from the cytosol to intracellular membranes, release of cytochrome c from the mitochondria, activation of caspase-3, poly(ADP-ribose)polymerase (PARP) cleavage, and DNA fragmentation. All of these events were inhibited in H9c2 cells overexpressing ARC when compared with control cells. In contrast, caspase inhibitors prevented PARP cleavage but not cytochrome c release, suggesting that exogenously expressed ARC acts upstream of caspase activation in this model of apoptosis. These results demonstrate that ARC can protect heart myogenic H9c2 cells from hypoxia-induced apoptosis, and that ARC prevents cytochrome c release by acting upstream of caspase activation, perhaps at the mitochondrial level.

Animals↗
PubMed1999

An alternatively spliced surfactant protein B mRNA in normal human lung: disease implication.

We identified an alternatively-spliced surfactant protein B (SP-B) mRNA from normal human lung with a 12 nt deletion at the beginning of exon 8. This deletion causes a loss of four amino acids in the SP-B precursor protein. Sequence comparison of the 3' splice sites reveals only one difference in the frequency of U/C in the 11 predominantly-pyrimidine nucleotide tract, 73% for the normal and 45% for the alternatively-spliced SP-B mRNA (77-99% for the consensus sequence). Analysis of SP-B mRNA in lung indicates that the abundance of the alternatively-spliced form is very low and varies among individuals. Although the relative abundance of the deletion form of SP-B mRNA remains constant among normal lungs, it is found with relatively higher abundance in the lungs of some individuals with diseases such as congenital alveolar proteinosis, respiratory distress syndrome, bronchopulmonary dysplasia, alveolar capillary dysplasia and hypophosphatasia. This observation points to the possibility that the alternative splicing is a potential regulatory mechanism of SP-B and may play a role in the pathogenesis of disease under certain circumstances.

Alternative Splicing↗
PubMed1999

Genetic studies on a family with acute myelogenous leukemia.

Seven cases of myelogenous leukemia--two acute erythroleukemia (AEL), four acute myelogenous leukemia (AML), and one acute myelomonocytic leukemia (AMMoL)--were found in 22 members of three consecutive generations of a family in the past 16 years (1973-1989). By using cytogenetic, hematologic, and biochemical analyses of those surviving in this family, we also found four members who might develop leukemia in the future. Southern blot analysis of one of the four members and her father (an acute leukemia patient) with a v-ERBB probe showed that the gene abnormalities consisted of a c-ERBB rearrangement (hereditary) and a rearrangement/amplification of the same gene.

Blotting, Southern↗
PubMed1999

Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons.

The N-type Ca channel alpha1B subunit is localized to synapses throughout the nervous system and couples excitation to release of neurotransmitters. In a previous study, two functionally distinct variants of the alpha1B subunit were identified, rnalpha1B-b and rnalpha1B-d, that differ at two loci;four amino acids [SerPheMetGly (SFMG)] in IIIS3-S4 and two amino acids [GluThr (ET)] in IVS3-S4. These variants are reciprocally expressed in rat brain and sympathetic ganglia (). We now show that the slower activation kinetics of rnalpha1B-b (DeltaSFMG/+ET) compared with rnalpha1B-d (+SFMG/DeltaET) channels are fully accounted for by the insertion of ET in IVS3-S4 and not by the lack of SFMG in IIIS3-S4. We also show that the inactivation kinetics of these two variants are indistinguishable. Through genomic analysis we identify a six-base cassette exon that encodes the ET site and with ribonuclease protection assays demonstrate that the expression of this mini-exon is essentially restricted to alpha1B RNAs of peripheral neurons. We also show evidence for regulated alternative splicing of a six-base exon encoding NP in the IVS3-S4 linker of the closely related alpha1A gene and establish that residues NP can functionally substitute for ET in domain IVS3-S4 of alpha1B. The selective expression of functionally distinct Ca channel splice variants of alpha1B and alpha1A subunits in different regions of the nervous system adds a new dimension of diversity to voltage-dependent Ca signaling in neurons that may be important for optimizing action potential-dependent transmitter release at different synapses.

Action Potentials↗
PubMed1999

Laboratory evolution of peroxide-mediated cytochrome P450 hydroxylation.

Enzyme-based chemical transformations typically proceed with high selectivity under mild conditions, and are becoming increasingly important in the pharmaceutical and chemical industries. Cytochrome P450 monooxygenases (P450s) constitute a large family of enzymes of particular interest in this regard. Their biological functions, such as detoxification of xenobiotics and steroidogenesis, are based on the ability to catalyse the insertion of oxygen into a wide variety of compounds. Such a catalytic transformation might find technological applications in areas ranging from gene therapy and environmental remediation to the selective synthesis of pharmaceuticals and chemicals. But relatively low turnover rates (particularly towards non-natural substrates), low stability and the need for electron-donating cofactors prohibit the practical use of P450s as isolated enzymes. Here we report the directed evolution of the P450 from Pseudomonas putida to create mutants that hydroxylate naphthalene in the absence of cofactors through the 'peroxide shunt' pathway with more than 20-fold higher activity than the native enzyme. We are able to screen efficiently for improved mutants by coexpressing them with horseradish peroxidase, which converts the products of the P450 reaction into fluorescent compounds amenable to digital imaging screening. This system should allow us to select and develop mono- and di-oxygenases into practically useful biocatalysts for the hydroxylation of a wide range of aromatic compounds.

Catalysis↗
PubMed1999

Chicoric acid analogues as HIV-1 integrase inhibitors.

The present study was undertaken to examine structural features of L-chicoric acid (3) which are important for potency against purified HIV-1 integrase and for reported cytoprotective effects in cell-based systems. Through a progressive series of analogues, it was shown that enantiomeric D-chicoric acid (4) retains inhibitory potency against purified integrase equal to its L-counterpart and further that removal of either one or both carboxylic functionalities results in essentially no loss of inhibitory potency. Additionally, while two caffeoyl moieties are required, attachment of caffeoyl groups to the central linking structure can be achieved via amide or mixed amide/ester linkages. More remarkable is the finding that blockage of the catechol functionality through conversion to tetraacetate esters results in almost no loss of potency, contingent on the presence of at least one carboxyl group on the central linker. Taken as a whole, the work has resulted in the identification of new integrase inhibitors which may be regarded as bis-caffeoyl derivatives of glycidic acid and amino acids such as serine and beta-aminoalanine. The present study also examined the reported ability of chicoric acid to exert cytoprotective effects in HIV-infected cells. It was demonstrated in target and cell-based assays that the chicoric acids do not significantly inhibit other targets associated with HIV-1 replication, including reverse transcription, protease function, NCp7 zinc finger function, or replication of virus from latently infected cells. In CEM cells, for both the parent chicoric acid and selected analogues, antiviral activity was observable under specific assay conditions and with high dependence on the multiplicity of viral infection. However, against HIV-1- and HIV-2-infected MT-4 cells, the chicoric acids and their tetraacetylated esters exhibited antiviral activity (50% effective concentration (EC50) ranging from 1.7 to 20 microM and 50% inhibitory concentration (IC50) ranging from 40 to 60 microM).

Animals↗
PubMed1999

An issue of statistical analysis in controlled multi-centre studies: how shall we weight the centres?

When analysing data from a controlled multi-centre study, an important issue is how to weight each centre to assess the overall treatment effect. The unweighted analysis, which weights all centres equally, was recommended by many statisticians and the U.S. Food and Drug Administration, and has been routinely utilized as the primary statistical method for many phase III clinical studies in the pharmaceutical industry. The weighted analysis, which weights centres relative to the number of patients in them, was considered not meaningful in the presence of treatment-by-centre interaction. This paper demonstrates why we should hesitate to use the unweighted analysis as the primary statistical method of a study from a statistical power perspective. It also shows that the weighted analysis is meaningful, even in the presence of treatment-by-centre interaction, and that it is generally the preferred approach.

Controlled Clinical Trials as Topic↗
PubMed1999

A high-throughput digital imaging screen for the discovery and directed evolution of oxygenases.

BACKGROUND: Oxygenases catalyze the hydroxylation of a wide variety of organic substrates. An ability to alter oxygenase substrate specificities and improve their activities and stabilities using recombinant DNA techniques would expand their use in processes such as chemical synthesis and bioremediation. Discovery and directed evolution of oxygenases require efficient screens that are sensitive to the activities of interest and can be applied to large numbers of crude enzyme samples. RESULTS: Horseradish peroxidase (HRP) couples the phenolic products of hydroxylation of aromatic substrates to generate colored and/or fluorescent compounds that are easily detected spectroscopically in high-throughput screening. Coexpression of the coupling enzyme with a functional mono- or dioxygenase creates a pathway for the conversion of aromatic substrates into fluorescent compounds in vivo. We used this approach for detecting the products of the toluene-dioxygenase-catalyzed hydroxylation of chlorobenzene and to screen large mutant libraries of Pseudomonas putida cytochrome P450cam by fluorescence digital imaging. Colors generated by the HRP coupling reaction are sensitive to the site of oxygenase-catalyzed hydroxylation, allowing the screen to be used to identify catalysts with new or altered regiospecificities. CONCLUSIONS: The coupled oxygenase-peroxidase reaction system is well suited for screening oxygenase libraries to identify mutants with desired features, including higher activity or stability and altered reaction specificity. This approach should also be useful for screening expressed DNA libraries and combinatorial chemical libraries for hydroxylation catalysts and for optimizing oxygenase reaction conditions.

Camphor 5-Monooxygenase↗
PubMed1999

Gastric myoelectrical activity in patients with Parkinson's disease: evidence of a primary gastric abnormality.

Parkinson's disease patients may experience various gastrointestinal symptoms; however, the exact pathophysiology of these symptoms is not fully understood. Therefore, the aim of this study was to investigate the pattern of gastric myoelectrical activity in patients with Parkinson's disease. Eleven patients with Parkinson's disease and 10 healthy subjects participated in the study. Patients were stratified as "receiving dopaminergic therapy" (N = 5) and "off therapy" (N = 6). Gastric myoelectrical activity was measured by means of surface electrogastrography (EGG) for 30 min before and for 90 min after a standardized meal. The dominant frequency, postprandial EGG power change, and the percentage of normal 2-4 cycles/min (cpm) slow-wave activity in the three groups were calculated and compared. The mean postprandial EGG power increase in the untreated patients was smaller than in the treated patients (-3.11 +/- 1.01 and 1.17 +/- 1.96 dB; P = 0.072). Moreover, both of these values were significantly decreased when compared to the control group (untreated vs control: -3.11 +/- 1.01 vs 8.01 +/- 1.86 dB; P = 0.04 and treated vs control: 1.17 +/- 1.96 vs 8.01 +/- 1.86 dB; P = 0.02). The percentage of normal 2-4 cpm slow waves in untreated patients was not different from the treated patients (82.6 +/- 6.6% vs 75.8 +/- 13.6%, P = NS) or from the control group (88.2 +/- 5.4%, P = NS). The dominant frequency after the meal was similar to that in the fasting state both in the untreated (3.3 +/- 0.1 vs 3.2 +/- 0.2 cpm; P = NS) and treated patients (3.2 +/- 0.1 vs 3.1 +/- 0.1 cpm, P = NS), whereas the dominant frequency significantly increased postprandially in the control group (2.88 +/- 0.12 vs 3.05 +/- 0.16; P < 0.05). Abnormalities in gastric myoelectrical activity in untreated Parkinson's disease patients reflect direct involvement of the gastrointestinal tract by the primary disease process. EGG can be regarded as a useful diagnostic tool in evaluating gastrointestinal involvement in neurodegenerative diseases.

Aged↗
PubMed1999

Calcium channel activation stabilizes a neuronal calcium channel mRNA.

We have identified a calcium-dependent pathway in neurons that regulates expression levels of the alpha1B subunit and N channel current. When neurons are depolarized and voltage-gated calcium channels activated, the half-life of cellular N channel alpha1B mRNA is prolonged. This stabilizing effect of depolarization is mediated through the 3' untranslated region of a long form of the alpha1B mRNA and may represent a form of modulation of N-channel levels that does not require changes in gene transcription. Increases in N channel expression would affect several key neuronal functions controlled by calcium, including transmitter release and neurite outgrowth.

3' Untranslated Regions↗
PubMed1999

Stimulation of mouse melanocyte proliferation by Piper nigrum fruit extract and its main alkaloid, piperine.

During a herbal screening programme to find potential repigmenting agents for the treatment of vitiligo, Piper nigrum L. fruit (black pepper) extract was found to possess growth-stimulatory activity towards cultured melanocytes. Its aqueous extract at 0.1 mg/ml was observed to cause nearly 300% stimulation of the growth of a cultured mouse melanocyte line, melan-a, in 8 days (p < 0.01). Piperine (1-piperoylpiperidine), the main alkaloid from Piper nigrum fruit, also significantly stimulated melan-a cell growth. Both Piper nigrum extract and piperine induced morphological alterations in melan-a cells, with more and longer dendrites observed. The augmentation of growth by piperine was effectively inhibited by RO-31-8220, a selective protein kinase C (PKC) inhibitor, suggesting that PKC signalling is involved in its activity. This is the first full report on such an activity of black pepper and piperine.

Alkaloids↗
PubMed1999

Gastric myoelectric activity in patients with end-stage liver disease.

BACKGROUND: Abnormalities of gastrointestinal motility and transit time have been reported in association with end-stage liver disease. Motility abnormalities could be routinely studied if a simple noninvasive test were available. The electrogastrogram is a cutaneous measure of gastric myoelectric activity and correlates well with serosal recordings of gastric myoelectric activity. The aim of this study was to evaluate gastric myoelectric activity in patients with end-stage liver disease. METHODS: Fourteen patients with end-stage liver disease had gastric myoelectric activity measured with the electrogastrogram. An electrogastrogram was considered abnormal when normal gastric slow waves were seen less than 70% of the time or there was no increase in the electrogastrogram amplitude after a meal. RESULTS: Abnormal electrogastrograms were present in 8 of 14 (57%) end-stage liver disease patients. CONCLUSIONS: Abnormal gastric myoelectric activity is common in end-stage liver disease.

Adult↗
PubMed1999

The molecular basis of Sjögren-Larsson syndrome: mutation analysis of the fatty aldehyde dehydrogenase gene.

Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder characterized by ichthyosis, mental retardation, spasticity, and deficient activity of fatty aldehyde dehydrogenase (FALDH). To define the molecular defects causing SLS, we performed mutation analysis of the FALDH gene in probands from 63 kindreds with SLS. Among these patients, 49 different mutations-including 10 deletions, 2 insertions, 22 amino acid substitutions, 3 nonsense mutations, 9 splice-site defects, and 3 complex mutations-were found. All of the patients with SLS were found to carry mutations. Nineteen of the missense mutations resulted in a severe reduction of FALDH enzyme catalytic activity when expressed in mammalian cells, but one mutation (798G-->C [K266N]) seemed to have a greater effect on mRNA stability. The splice-site mutations led to exon skipping or utilization of cryptic acceptor-splice sites. Thirty-seven mutations were private, and 12 mutations were seen in two or more probands of European or Middle Eastern descent. Four single-nucleotide polymorphisms (SNPs) were found in the FALDH gene. At least four of the common mutations (551C-->T, 682C-->T, 733G-->A, and 798+1delG) were associated with multiple SNP haplotypes, suggesting that these mutations originated independently on more than one occasion or were ancient SLS genes that had undergone intragenic recombination. Our results demonstrate that SLS is caused by a strikingly heterogeneous group of mutations in the FALDH gene and provide a framework for understanding the genetic basis of SLS and the development of DNA-based diagnostic tests.

Aldehyde Oxidoreductases↗