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Biomedical subjects

B Yan

Publications and source records attributed to B Yan.

At least 91 records · Page 5Linked to original sources

[Controlled clinical study on efficacy of fixed-dose compounds rifater/rifinah in antituberculous chemotherapy].

OBJECTIVE: To assess antituberculous efficacy, patients' compliance and application perspective of fixed-dose compounds rifater/rifinah in China. METHOD: Three hundred eight new smear positive pulmonary tuberculosis patients were randomly allocated with a ratio of 2 to 1 into treatment group (227 cases, receiving 2RIFATER/4RIFINAH regimen) and controls (81 cases, 2HRZ/4HR) for observation. RESULT: The sputum negative conversion rates at the 2nd month in the treatment group and the controls were 91.2% and 86.4% respectively, and at the end of the chemotherapy 98.7% and 97.5%. Chest radiography showed remarkable improvement. The resolution of pulmonary lesions in the treatment group and the controls accounted for 95.2% and 93.8% respectively, with cavity closure rates of 68.6% in the treatment group and 67.9% in the controls. The drug adverse reaction rates were 8.9% in both groups, and the default rates were 4.3% and 7.8% respectively. CONCLUSION: Fixed-dose compounds rifater/rifinah show excellent therapeutic efficacy, safety and compliance in antituberculous chemotherapy, which could be recommended for wider use in tuberculosis control in China.

Adolescent↗

[Multiple dose pharmacokinetic and bioavailability studies of oral sustained release and conventional formulations of isosorbide-5-mononitrate in healthy volunteers].

The pharmacokinetics of a new sustained release tablets (40 mg, qd) of isosorbide-5-mononitrate (IS-5-MN) was investigated together with a conventional preparation (20 mg, bid) after multiple oral administration in ten healthy human subjects using an open, randomized two-way crossover experimental design. Based on three statistical analyses of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be bioequivalent (P > 0.1), with a relative bioavailability of 108.95% for the IS-5-MN sustained release formulation. Pharmacokinetic data showed that the sustained release formulation reached mean peak plasma levels significantly later and lower minimum plasma concentration (Cmin), compared with the conventional preparation. But no statistically significant difference was found for other pharmacokinetic parameters including peak plasma levels (Cmax), AUC, elimination constant (Ke), elimination half-life (T1/2) and fluctuation index (FI) between the two preparations (P > 0.05).

Adult↗

Single and multiple dose pharmacokinetic studies of oral sustained release and non-sustained release formulations of isosorbide-5-mononitrate in healthy volunteers.

The pharmacokinetics of a new sustained release tablet (40 mg, "test") of isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) was investigated together with a reference preparation (20 mg, "reference") after single and multiple oral administration in ten healthy human subjects using an open, randomised two-way crossover experimental design. Based on the statistical evaluation of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be the same with regard to the amount absorbed. Pharmacokinetic data showed that with the test tablet significantly lower and delayed mean peak plasma levels (Cmax) were reached compared with the reference preparation in both single and multiple dose studies. The test formulation also produced lower minimum plasma concentration (Cmin). However, there was no statistically significant difference for other pharmacokinetic parameters, including the elimination rate constant (Kel), the elimination half-life (t1/2) and the peak-trough fluctuation constant (PTF) between the two treatments. It was demonstrated that the new sustained release formulation of isosorbide-5-mononitrate could be useful in clinical practice for the treatment of angina pectoris and congestive heart failure.

Adult↗

Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters.

Induction of islet neogenesis by cellophane wrapping (CW) reverses streptozotocin-induced (STZ) diabetes. Administration of Ilotropin, a protein extract isolated from CW pancreata, causes recapitulation of normal islet ontogeny and reverses STZ diabetes, reducing mortality by 50%. We investigated the hypothesis that a novel gene encoding a constituent of Ilotropin was expressed in the hamster pancreas undergoing islet neogenesis. Islet neogenesis associated protein (INGAP) is a product of a novel gene expressed in regenerating hamster pancreas. Northern blot analysis showed a strong single transcript of 850 bp at 1 and 2 d after CW that disappeared by the 6th day and was absent from untreated control pancreata. INGAP gene is expressed in acinar cells, but not in islets. Western blot analysis demonstrated the presence of INGAP in Ilotropin but not in extracts from control pancreata. A synthetic pentadecapeptide, corresponding to a region unique to INGAP, stimulated a 2.4-fold increase in [3H]thymidine incorporation into hamster duct epithelium in primary culture and a rat pancreatic duct cell line but had no effect on a hamster insulinoma tumor cell line. A portion of human INGAP gene was cloned and appears to be highly homologous to the hamster gene. This data suggests that the INGAP gene is a novel pancreatic gene expressed during islet neogenesis whose protein product is a constituent of Ilotropin and is capable of initiating duct cell proliferation, a prerequisite for islet neogenesis.

Amino Acid Sequence↗

Cytokines (IL-1beta and TNFalpha) in relation to biochemical and immunological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats.

Previous studies in different strains of rats and mice have shown that the inhibition of gluconeogenesis as a result of reduced liver phosphoenolpyruvate carboxykinase (PEPCK) activity together with appetite suppression play critical roles in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent immunological studies in rats demonstrated that exposure to low doses of TCDD resulted in an early and enhanced IgG response to immunization with sheep red blood cells (SRBC) and an enhanced delayed-type hypersensitivity (DTH) reaction as well as a positive popliteal lymph node (PLN) response. However, high doses of TCDD suppressed the DTH reaction. This study aimed at examining the involvement of cytokines (IL-1 and TNF) in mediating the above effects. Liver samples from a previous dose-response study on DTH reaction were investigated, in which rats were treated with TCDD (1, 3, 10, 30 and 90 microg/kg) and immunized with an antigen. mRNA levels of IL-1beta were elevated begining at the 1 microg/kg (non-lethal) dosage group with a maximum increase of about 5-fold above controls in the 90 microg/kg (lethal) dosage group. mRNA levels of TNFalpha were also significantly elevated begining at the 30 microg/kg dosage group. These results suggest that at low doses of TCDD, increased IL-1beta could be responsible for immune function stimulation, whereas at high doses of TCDD, greatly elevated TNFalpha and IL-1beta levles may exacerbate or mediate acute toxicity including immune suppression and related biochemical effects. A time course study (60 microg TCDD/kg without immunization) revealed that liver mRNA levels of TNFalpha were significantly elevated starting 24 h, and reaching a maximum 48 h after dosing with TCDD. This change was accompanied by a transient increase of mRNA levels of IL-1beta at day 4 after TCDD dosage. Thus, these data demonstrated that TCDD alone (without immunization) can cause transient increases of mRNA levels of TNFalpha and IL-1beta in liver. Results from these experiments suggest that TCDD-induced cytokine changes may play important roles in various effects of TCDD.

Animals↗

Transcriptional initiation sites in sorghum mitochondrial DNA indicate conserved and variable features.

Transcriptional initiation and processing was examined for three sorghum mitochondrial DNA genes (atp6-1, atp6-2, urf209) and two open reading frames (orf265/130, orf107) to characterize sequences associated with initiation and other transcriptional strategies for this species. The 5' termini of ten transcripts were determined by primer extension, and mtRNA was capped with guanylyl transferase and annealed to anti-sense riboprobes to identify transcriptional initiation regions. Eight transcript termini were suitable substrates for guanylyl transferase, indicating the presence of one (atp6-1, atp6-2, urf209), two (orf265/130), or three (orf107) promoters for the five examples. The majority of the putative promoters were associated with single primer-extension termini, while two examples exhibited two transcript-initiation sites within the promoter. Four examples were characterized by initiated transcripts without subsequent processing, indicating that processing is not obligatory. Each of the putative promoter regions included significant A/T-rich 5' regions, consistent with previous examples, but four exceptions to a consensus core YRTA sequence were identified. The anomalies (AATA, CTTA) suggest plasticity in the primary structure of the core region of higher-plant mitochondrial DNA promoters.

Base Sequence↗

Different distribution of fluorinated anesthetics and nonanesthetics in model membrane: a 19F NMR study.

Despite their structural resemblance, a pair of cyclic halogenated compounds, 1-chloro-1,2,2-trifluorocyclobutane (F3) and 1,2-dichlorohexafluorocyclobutane (F6), exhibit completely different anesthetic properties. Whereas the former is a potent general anesthetic, the latter produces no anesthesia. Two linear compounds, isoflurane and 2,3-dichlorooctofluorobutane (F8), although not a structural pair, also show the same anesthetic discrepancy. Using 19F nuclear magnetic spectroscopy, we investigated the time-averaged submolecular distribution of these compounds in a vesicle suspension of phosphatidylcholine lipids. A two-site exchange model was used to interpret the observed changes in resonance frequencies as a function of the solubilization of these compounds in membrane and in water. At clinically relevant concentrations, the anesthetics F3 and isoflurane distributed preferentially to regions of the membrane that permit easy contact with water. The frequency changes of these two anesthetics can be well characterized by the two-site exchange model. In contrast, the nonanesthetics F6 and F8 solubilized deeply into the lipid core, and their frequency change significantly deviated from the prediction of the model. It is concluded that although anesthetics and nonanesthetics may show similar hydrophobicity in bulk solvents such as olive oil, their distributions in various regions in biomembranes, and hence their effective concentrations at different submolecular sites, may differ significantly.

Anesthetics↗

Transcription initiation sites for sorghum mitochondrial atp9 are positioned immediately 3' to trnfM.

Sorghum mitochondrial atp9 is polymorphic among male-sterile cytoplasms, but each cytoplasm is characterized by a major 650 nt transcript, regardless of fertility status. The gene is positioned 323 bp 3' to trnfM. Primer extension revealed multiple atp9 5' transcript termini, distributed from +1 to +28 3' to trnfM; the termini could be labeled with polynucleotide kinase, suggesting that they result from the maturation of trnfM. Guanylyltransferase experiments, however, showed that four of the termini were capable. The juxtaposition of a putative promoter 3' to trnfM results in a unique atp9 transcript population consisting of primary and processed transcripts.

Amino Acid Sequence↗

Circular dichroism studies in conformation of cellobiohydrolase and endoglucanase from Trichoderma pseudokiningii S-38: effects of pH and ligand binding.

Effects of pH and ligand binding upon the conformation of cellobiohydrolase I (CBHI) and endoglucanase I (EGI) from Trichoderma pseudokiningii S-38 have been studied by circular dichroism measurements. In the high-pH range (6-9), increasing pH resulted in a similar conformational change occurring in free CBHI and EGI, while such treatment gave different changes of the two enzyme conformations in the presence of cellobiose. On the other hand, in the low-pH region, with both CBHI an EGI in the active form, decreasing pH resulted in a large conformational change of free EGI compared to that of free CBHI, whereas ligand binding resulted in a similar change of both CBHI and EGI, independent of pH change.

Cellobiose↗

Three-dimensional model of sensory rhodopsin I reveals important restraints between the protein and the chromophore.

A structural model is constructed for the integral membrane protein, sensory rhodopsin I (SRI), the phototaxis receptor of the archaeon Halobacterium salinarium. The model is built on the template of the homologous bacteriorhodopsin (BR). The modeling procedure includes sequence alignment, a side chain rotamer search and simulated annealing by restricted molecular dynamics. The structure is in general agreement with previous results from mutagenesis experiments, chromophore substitution and room and cryogenic temperature spectroscopy. In particular, a residue near the beta-ionone ring of the retinylidene chromophore is found to be critical in maintaining the proper isomeric conformation of the chromophore; a layer of residues lying on the cytoplasmic side of the chromophore pocket is found to modulate the restraints around the C13 region of the chromophore, affecting the isomerizations around its 13 = 14 bond that are important to the protein's activity. The restraints in these regions are more stringent in SRI than in BR. The tightened restraints are chiefly due to van der Waals interactions, where the attractive and repulsive components play separable roles. Aromatic residues account for a majority of the restrictive interactions. It is hypothesized that the enhanced barriers due to these restrictions regulate the progress of SRI's photocycle, so that it can couple with the phototaxis reaction chain in the bacterium. A possibility is also suggested that conformational changes of the protein provide the signal recognized by the transducer.

Amino Acid Sequence↗

Beta-adrenoceptor activation-induced placental prorenin secretion is mediated by increased renin messenger RNA and protein synthesis.

Activation of beta-adrenoceptors has been shown to promote renin secretion in both human kidney and placenta. In kidney, the enhanced secretion is immediately observed, and mobilization of renin in the storage granules accounts for such a rapid response. In contrast, the enhanced secretion in placenta is delayed for 6-12 hr after receptor activation and consists almost entirely of the renin precursor prorenin. It is hypothesized that newly synthesized rather than stored enzyme is responsible for the enhanced secretion in human placenta. To test this hypothesis, placental explants were cultured in the presence or absence of the protein synthesis inhibitor cycloheximide, and prorenin concentrations in the tissue and medium were measured. Dobutamine and terbutaline, beta1- and beta2-adrenoceptor agonists, evoked 17- and 5-fold increases in secretion, respectively. Tissue content of prorenin in response to the treatment was increased by a similar magnitude, yet values were consistently <10% of medium concentrations. The increases in prorenin concentrations in both medium and tissue, however, were markedly attenuated by cycloheximide, suggesting that prorenin synthesis in response to beta-adrenoceptor activation is required. Reverse transcription coupled with polymerase chain reaction revealed that renin mRNA levels were increased by 3-8-fold and occurred before increases in tissue and medium prorenin, indicating that increased renin mRNA levels are responsible for the increased synthesis of prorenin. Explants cultured in the presence of actinomycin D, an inhibitor of transcription, did not show the agonist-induced prorenin mRNA levels or enhancement of its secretion. The peak levels of renin mRNA were reached after 6 hr of incubation, were sustained at similar levels after 24 hr, and were not affected by cycloheximide. These findings are consistent with the notion that enhancement of renin mRNA and de novo protein synthesis are required for prorenin secretion induced by activation of placental beta-adrenoceptors.

Adrenergic beta-Agonists↗

[Construction of mycobacterium tuberculosis genomic library].

OBJECTIVE: To provide effective tools for identification and characterization of M. tuberculosis genes/antigenes and to evaluate their roles in diagnosis, vaccination, drug resistance, and pathogenesis. METHODS: M. tuberculosis genomic DNA obtained from H 37 Ra strain was partially digested with DNase I. The DNA fragments ranging from 4-8 kb were isolated from agarose gel and ligated to EcoR I adaptor, and the products were linked to lamda gt11 arms and packaged using an in vitro packaging extract. The different diluted bacteriophages were used to transfect bacteria Y1090. RESULTS: The efficiency and titer of the library were 85% and 3 x 10(5) pfu/ml, respectively. The library contained 1.3 x 10(5) individual recombinant phage whose foreign DNA inserted fragment size was 3.5 kb on average. CONCLUSION: The genomic DNA library constructed here can provide sufficient clone to cover H37Ra gene.

Genome, Bacterial↗

Solid-state 13C-NMR spectroscopy of adduction products of 2,5-hexanedione with ribonuclease, albumin, and rat neurofilament protein.

The Paal-Knorr condensation reaction between the gamma-diketone 2,5-hexanedione (2,5-HD) and epsilon-amine moieties of proteins of various molecular weight, including ribonuclease (RNase), bovine serum albumin (BSA) and rat neurofilament (NF), has been investigated by solid-state 13C-NMR spectroscopy. These proteins all reacted with 2,5-HD with the formation of 2,5-dimethylpyrrole (2,5-DMP) derivatives. The size and complexity of the protein affected the rate of formation of 2,5-DMP derivatives. Using the selective reducing reagent NaCNBH3, the Paal-Knorr reaction intermediates were trapped by conversion into amines, which were identified by solid-state NMR spectroscopy. The secondary autoxidation reaction following the formation of 2,5-DMP derivatives was also studied by solid-state NMR spectroscopy.

Animals↗

Sorghum mitochondrial orf25 and a related chimeric configuration of a male-sterile cytoplasm.

We describe fundamental characteristics of sorghum mitochondrial orf25, urf209, and a related chimeric configuration, orf265/130, which is restricted to the IS1112C source of cytoplasmic male sterility in sorghum. Transcripts of urf209 are edited at ten nucleotides, resulting in nine amino-acid changes predicted from genomic sequences. The cDNA-predicted polypeptide product is 23.6 kDa, while Western blot analyses identify a product of 20k Da. Transcription of urf209 is characterized by one or two transcripts, dependent on nuclear background, but this difference is not related to male fertility status. The orf265/130 chimeric region includes 288 bp 95% identical to sequences 5' to maize T-cytoplasm T-urf13 and atp6, which includes a common transcription initiation site, and terminates with a recombinational event involving urf209. The urf209 similarity extends 189 bp, followed by sequences duplicated 5' to sorghum atp6-2. Sequences immediately 3' to the atp6-2 similarity include a second in-frame start codon, defining orf130. Structural features 5' to orf130 are shared with motifs found 5' to several translated mitochondrial open reading frames. The orf265/orf130 configuration is uniquely transcribed, and transcripts of orf130 exhibit one silent RNA editing event. Transcription in somatic cells is not altered by male fertility status.

Amino Acid Sequence↗