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Biomedical subjects

A Zhang

Publications and source records attributed to A Zhang.

At least 127 records · Page 7Linked to original sources
PubMed1996

Synthesis and activity of piperazine-containing antirhinoviral agents and crystal structure of SDZ 880-061 bound to human rhinovirus 14.

A series of antipicornaviral agents containing piperazinyl moieties was synthesized with the objective of obtaining a compound with a broad spectrum of antirhinovirus activity, high potency (< or = 0.003 microgram/ml), and low cytotoxicity (> or = 30 micrograms/ml). Five compounds of this series were evaluated in detail for efficacy against various HRV serotypes. The agent SDZ 880-061, containing the benzothiazine moiety SDZ 108-075, which is particularly active against HRV14, and the thiazolyl acetic acid ester group of SDZ 89-124, which is potent against HRV1B, indeed has a relatively broad antiviral spectrum. SDZ 880-061 inhibited 85% of 89 HRV serotypes tested at a concentration of < or = 3 micrograms/ml. The 3.0 A resolution X-ray structure of SDZ 880-061 bound to HRV14 has revealed the binding characteristics of this potent compound. It binds in the same pocket as other capsid-binding antiviral agents characterized to date, leaving the innermost portion of the pocket vacant. The binding causes similar, although less extensive, alterations of the HRV14 VP1 backbone conformation (residues 100 to 110, 151 to 159, and 213 to 224) compared to other antiviral agents analyzed structurally. Although the contacts between SDZ 880-061 and HRV14 are mostly of hydrophobic character, the inhibitor has three relatively short polar interactions with residues of VP1 that represent potential hydrogen bonds. The amount of solvent-accessible surface area of SDZ 880-061 buried in the complex (613 A2) is within the range of that observed in protein-protein interfaces. The observed influence of time of addition or removal of SDZ 880-061 on virus yield and on the infectious-center formation indicates that the compound primarily interferes with HRV14 cellular attachment. Since it is assumed that uncoating requires virion instability and/or flexibility, the finding that SDZ 880-061 has only a marginal effect on uncoating may be due to the fact that it does not completely fill the hydrophobic pocket.

Antiviral Agents↗
PubMed1996

Escherichia coli protein analogs StpA and H-NS: regulatory loops, similar and disparate effects on nucleic acid dynamics.

Expression of the Escherichia coli StpA protein was investigated and a functional comparison undertaken with the structurally analogous nucleoid protein H-NS. Analysis of stpA and hns expression indicated that although stpA transcript levels are much lower than those of hns, the two gene products are capable of both negative autogenous control and cross-regulation. Examination of cellular proteins in stpA, hns, or stpA-hns backgrounds revealed that StpA can repress and activate a subset of H-NS-regulated genes. Mechanistic parallels in regulation of gene expression are indicated by the ability of both proteins to inhibit transcription from promoters containing curved DNA sequences, and to form nucleoprotein structures that constrain DNA supercoils. Despite their functional similarities, each molecule is capable of independent activities. Thus, H-NS regulates a class of genes that are unaffected by StpA in vivo, whereas StpA has much stronger RNA chaperone activity in vitro. We therefore propose that in addition to its role as a molecular back-up of H-NS, StpA's superior effect on RNA may be exploited under some specific cellular conditions to promote differential gene expression.

Bacterial Outer Membrane Proteins↗
PubMed1996

Chloride secretion in the submandibular gland of adult and early postnatal rats studied by X-ray microanalysis.

Submandibular acinar cells of 1-day-old, 7-day-old, and adult rats were analyzed with X-ray microanalysis after stimulation with carbachol for different time periods (2-7 min). In unstimulated animals, marked differences in elemental content between compartments could be observed: secretory granules had a higher Ca and lower P and K content than other cell compartments. Comparison between different age groups showed significant differences for Ca, which increased with age in all compartments; Mg increased with age in the secretory granules and the apical cytoplasm. Only the glands from adult animals showed a significant effect of cholinergic stimulation: a transient decrease in Cl and K. The Cl concentration in the secretory granules decreased to 60% of the control value, which suggests that the granules release Cl upon stimulation. In young animals, no or little change in elemental distribution was observed after stimulation. This may indicate that Cl- secretion mechanisms are much less prominent in young animals. The ultrastructure of submandibular secretory granules depends on the preparation method: condensed and electrondense in freeze-substituted unfixed tissue, decondensed and more translucent in aldehyde-fixed tissue. This may indicate that the granules can transport water, and swell during the process of aldehyde fixation.

Aging↗
PubMed1996

Multicenter study of target-controlled infusion of propofol-sufentanil or sufentanil-midazolam for coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: The use of target-controlled infusions of anesthetics for coronary artery bypass graft surgery has not been studied in detail. The effects of target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were evaluated and compared. METHODS: At 14 clinical sites, 329 patients were given a target-controlled infusion of propofol (n = 165) to produce effect-site concentration (Ce) of > or = 3-micrograms/ml or a target-controlled infusion of sufentanil (n = 164). Sufentanil or midazolam, respectively, also were infused. Systolic hypertension, hypotension, tachycardia, and bradycardia were assessed by measuring heart rate and blood pressure every minute during operation. Myocardial ischemia was assessed perioperatively by monitoring ST segment deviation via continuous three-lead Holter electrocardiography, and it was evaluated during operation by monitoring left ventricular wall motion abnormality via transesophageal echocardiography. RESULTS: The measured cardiovascular parameters were satisfactory and usually similar for the patients receiving propofol-sufentanil or sufentanil-midazolam. The primary endpoint of the percentage of patients with intraoperative ST segment deviation (23 +/- 6% vs. 24 +/- 6%, P = 0.86) did not differ significantly between the two groups. The incidence of left ventricular wall motion abnormality shown on transesophageal echocardiography before (19 +/- 4% vs. 26 +/- 4%, P = 0.25) and after (23 +/- 4% vs. 31 +/- 5%, P = 0.32) cardiopulmonary bypass also did not differ significantly for the two groups. Changes in intraoperative target concentration were more frequent with propofol-sufentanil anesthetic than with sufentanil-midazolam (11.7 +/- 7.1 vs. 7.3 +/- 3.6, P < 0.001). The incidence of intraoperative hypotension (77% vs. 55%, P < 0.001), the use of inotropic/vasopressor medications (93% vs. 84%, P = 0.01), and the administration of crystalloids (2.8 +/- 1.4 L vs. 2.4 +/- 1.2 L, P < 0.001) were significantly greater in the propofol-sufentanil group. Conversely, the incidence of intraoperative hypertension (43% vs. 54%, P = 0.05) and the use of antihypertensive/vasodilator medications (70% vs. 90%, P < 0.001) were significantly less in the propofol-sufentanil group. CONCLUSIONS: Target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were suitable to provide anesthesia for coronary artery bypass graft surgery. Continuous monitoring revealed a high prevalence of hemodynamic abnormalities. Despite greater hypotension in the propofol-sufentanil group and greater hypertension in the sufentanil-midazolam group, episodes of myocardial ischemia were similar for both groups and were not temporally related to episodes of hemodynamic abnormalities.

Aged↗
PubMed1996

[Restricting effects of geologic background system on genuine crude drugs in Sichuan].

The distribution, growth, output and quality of genuine crude drugs are restricted by geologic background system (GBS), whose extensional vector system "rock-->soil-->medicinal plants" accomplishes the unity of geological grand cycle and biological pulmonary circulation. This article describes how genuine crude drugs in Sichuan, such as Coptis chinensis, etc. for example, are restricted by GBS.

Animals↗
PubMed1996

[Isolation and structure flucidation of alkaloids from the bulb of Fritillaria Wabuensis S.Y. Tang et S.C. Yueh].

Eight alkaloids were isolated from the bulb of Fritillaria Wabuensis S.Y. Tang et S.C. Yueh the best "Chuan Bei" cultivated in Sichuan province, which is efficacious against cough. Five of them are known, identified as imperialine (I), peimisine (II), ebeinone (III), isoverticine (IV), and imperialine-beta-N-oxide (V). All the signals for both 1H and 12C-NMR spectra of base (V) were assigned by 2D NMR experiments, and an X-ray structural data of alkaloid (V) was obtained for the first time.

Alkaloids↗
PubMed1996

Effects of nicotinamide on prevention and treatment of streptozotocin-induced diabetes mellitus in rats.

OBJECTIVE: To study the effect of nicotinamide (NAA) on prevention and treatment of STZ-induced diabetes mellitus in rats. MATERIAL AND METHODS: 30 Sprague-Dawley rats were randomly divided inot three groups: 20 rats were given NAA 1 g/kg/day intramuscularly (10 rats) or orally (10 rats) as experimental groups and the other 10 rats by normal saline orally as control group. Three days later, all 30 rats received streptozotocin (STZ) 55 mg/kg by intraperitioneal injection and took NAA or normal saline continuously as described above for 14 days. During the study, fasting blood glucose (FBG) was measured before and 72 hours after STZ injection and every 2-3 days later on with Glucometer, 24 hours urinary glucose excretion (UGE) was determined once every 4 days with glucose oxidase, body weight was determined every week, the volume of 24-hour water intake and urine excretion were determined twice and once a week respectively. RESULTS: Two weeks after STZ injection, FBG and 24 hours UGE of all rats taking NAA were normal or nearly normal, islet function and morphology revealed no significant differences compared with those of the normal, whereas all rats of control group remained hyperglycemic (> 16.6 mmol/L) and markedly higher 24 hours UGE as compared with the normal islets appeared atrophic with decrement of B cell population. CONCLUSIONS: The results showed that NAA may effectively prevent the occurrence of STZ-induced diabetes mellitus in rats, suggesting that NAA may be an effective agent for prevention and treatment of insulin-dependent diabetes mellitus (IDDM) in prediabetic and early stage of IDDM.

Animals↗
PubMed1996

[Influence of cerebral traumatic dementia treated with acupuncture at houxi and shenmen].

Sixty-two cerebral traumatic dementia patients were randomly divided into two groups acupuncture treatment group (Group A, 32 cases) and physical treatment group (Group B, 30 cases). The changes of MMSE scores and auditory P300 were observed before and after the treatment. It were found that the indexes in group A changed significantly (P < 0.05-0.001), and the indexes in group B didn't change significantly (P > 0.1-0.4). The therapeutic effect in group A was better than that in group B(P < 0.001). The results confirmed that the cognitive function of cerebral traumatic dementia patients was increased effectively with acupuncture at Houxi and Shenmen.

Acupuncture Points↗
PubMed1996

In vitro systems and cultured cells as specimens for X-ray microanalysis.

In vitro systems and cultured cells are recognized as useful systems in many areas of biomedical research, including X-ray microanalysis. To be reliable, in an vitro system should have an elemental composition close to that of the tissue in situ, react in the same way to stimuli, and retain the in situ regulation of ion transport. In the present paper, four of the most commonly used in vitro systems will be reviewed: incubated tissue slices (liver and pancreas), isolated glands (submandibular gland acini, sweat glands), primary cell cultures (sweat glands, endometrium), and cell lines (the colon cancer cell line T84, immortalized sweat gland cells). Incubation of tissue slices of liver in Krebs-Ringers buffer caused a significant increase in Na and Cl and a decrease in K. Initially, these changes were also observed in the pancreas, but here the values gradually returned to normal. Isolated submandibular gland acini, and isolated sweat gland ducts and coils react in a similar way to stimulation as their in situ counterparts. In primary cultures of coil cells, however, part of the cell population acquires different ion transport characteristics. Technically simplest is the use of cell lines originating from cancer cells (e.g., the T84 cell line) and immortalized cell lines. X-ray microanalysis not only confirms data on ion transport obtained with other techniques, but adds the possibility to investigate the presence of subpopulations within a culture.

Animals↗
PubMed1995

Asynchronous DNA replication between 15q11.2q12 homologs: cytogenetic evidence for maternal imprinting and delayed replication.

DNA replication kinetics of Prader-Willi/Angelman syndrome region of 15q11.2q12 was studied without synchronization in five human amniotic cell and five skin fibroblast strains with a marker 15 chromosome, i.e., 15p+ or der(15), as cytological marker to distinguish between the two homologs. BrdU-33258 Hoechst-Giemsa techniques were used to analyze and compare the late replication patterns in the 15q11.2q12 region between the homologs. Asynchronous replication between the homologs was observed in both amniocytes and fibroblasts. From cells of a marker 15 of known parental origin, the paternal 15q11.2q12 replicated earlier than that of the maternal 15 in 92%-95% of asynchronous metaphases. The remaining 5%-8% of asynchronous metaphases displayed maternal early/paternal late replication. This mosaic pattern of replication in the 15q11.2q12 region may be due to methylation mosaicism of genomic imprinting or a relative lack of self-control of replication. These results provide cytogenetic evidence of maternal imprinting and delayed replication in the 15q11.2q12 region.

Amniotic Fluid↗
PubMed1995

Effects of pravastatin on lipid levels, in vitro oxidizability of non-HDL lipoproteins and microalbuminuria in IDDM patients.

The effects of pravastatin on plasma lipid levels, in vitro oxidizability of the non-HDL fraction, metabolic control, urinary albumin excretion, and four serum enzymes (SGPT, SGOT, GT and CPK) were studied in 20 insulin-dependent diabetic patients (IDDM) with incipient nephropathy. The patients were divided into two groups and the study was carried out by a crossover design. After 12 weeks pravastatin treatment (20 mg daily), plasma cholesterol, LDL-cholesterol and apolipoprotein B (Apo B) decreased by 22, 19 and 15%, respectively. The thiobarbituric acid reactive substances (TBARS) formation and the oxidation lagtime of the non-HDL fraction during the in vitro incubation with copper were not changed before and after treatment. The HbA1c and blood glucose levels, urinary albumin excretion, SGOT, SGPT and GT were not influenced by pravastatin treatment. CPK activity was elevated after 12 weeks of pravastatin treatment, and this elevation persisted even after the 12 weeks placebo period. So, pravastatin could be used as an effective drug for IDDM patients with incipient nephropathy, but close monitoring of the CPK activity is recommended.

Adult↗
PubMed1995

Determination of manganese in Chinese tea leaves by a catalytic kinetic spectrophotometric method.

The catalytic effect of manganese(II) on the oxidation of Rhodamine B with potassium periodate in the presence of 1,10-phenanthroline in acetic acid-sodium acetate was studied. A catalytic kinetic spectrophotometric method for determination of manganese(II) was developed. Manganese in the range 0.1-5.0 ng ml-1 can be determined, and the detection limit is 0.02 ng ml-1. Manganese in Chinese tea leaves was successfully determined.

Catalysis↗
PubMed1995

Monitoring pH of otitis media effusion in chinchillas using fluorescence spectroscopy.

We have developed a fiber optic fluorometer to measure fluorescent signal intensities across an epithelium barrier. As a medically relevant example, we have measured the pH of the effusion formed during Hemophilus influenzae induced otitis media infection in the chinchilla, the classical animal model for human middle ear disease. Because the choice of antibiotic used in clinical therapy is dependent on the pH of the effusion, a noninvasive method of measuring pH is highly desirable. Using the fluorescent pH probe carboxy-seminapthorhodafluor, we were able to detect pH changes of 0.15 units in the pH range around 7.0. The development and resolution of the otitis media was followed with magnetic resonance imaging to confirm the presence of the effusion formed during the infection.

Animals↗
PubMed1995

Chimeras from a human rhinovirus 14-human immunodeficiency virus type 1 (HIV-1) V3 loop seroprevalence library induce neutralizing responses against HIV-1.

A chimeric virus library was designed whereby sequences corresponding to the V3 loop of human immunodeficiency virus type 1 (HIV-1) were presented on the surface of human rhinovirus 14. The V3 loop sequences consisted of a relatively conserved segment of seven amino acids and five adjacent residues that were allowed to vary in proportion to their seroprevalence among HIV-1 isolates of North America and Europe. A technique called random systematic mutagenesis was used to incorporate the composite V3 loop sequences flanked by zero to two randomized amino acids. This library could contain 2.7 x 10(8) members having diverse sequences and conformations. Immunoselection of a portion of this library by using two neutralizing V3 loop-directed monoclonal antibodies followed by selection for desirable growth and purification characteristics yielded a set of chimeric rhinoviruses, five of which are described. The inserted sequences in the five chimeras do not match those of any known isolate of HIV-1. Nonetheless, all five chimeras were neutralized by antibodies directed against different strains of HIV-1 and were able to elicit the production of antibodies that bind V3 loop peptides from diverse HIV-1 isolates. Moreover, antisera derived from four of the five chimeras were capable of neutralizing one or more strains of HIV-1 in cell culture. This study demonstrates that random systematic mutagenesis in conjunction with antibody screening is a powerful and efficient means to obtain antigenic chimeras with relevant immunogenic properties.

Amino Acid Sequence↗
PubMed1995

Escherichia coli protein StpA stimulates self-splicing by promoting RNA assembly in vitro.

An Escherichia coli gene, stpA, has been identified and cloned based on its ability to suppress the Td- phenotype of a resident, splicing-defective phage T4 td (thymidylate synthase) gene. The stpA gene, which was localized to 60.24 min on the E. coli chromosome, encodes a 15.3-kDa protein. Overproduction of StpA in vivo led to an increase in td pre-mRNA levels and modest enhancement of td mRNA:pre-mRNA ratios. Consistent with its in vivo effect, purified StpA promoted RNA splicing in vitro, and facilitated RNA annealing and strand exchange with model substrates. These results suggest that StpA promotes splicing of the intron by binding RNA nonspecifically, resolving misfolded precursor molecules and facilitating association of critical base pair elements. Furthermore, proteinase K treatment of StpA-assembled precursors prior to the initiation of the splicing reaction still resulted in splicing enhancement, indicating that StpA is not required for the catalytic step, unlike the Neurospora splicing effector CYT-18, whose presence was necessary for catalysis to proceed. Together these results suggest that StpA has chaperone activity in vitro, with the property of promoting assembly of the precursors into an active conformation, in contrast to splicing effectors that stabilize the catalytically active intron structure.

Amino Acid Sequence↗
PubMed1995

[Studies on the deltamethrin-medicated bath of domestic dogs for interrupting visceral leishmaniasis transmission].

In a previous paper, it was reported that deltamethrin-medicated bath of domestic dogs had a strong killing effect against Ph. chinensis, and could also inhibit its blood sucking ability or cause its death shortly after blood sucking. The effect could last for 30 days to 114 days, and mostly for 2 months in the local area. Based on our previous study, three villages (Yongle, Yongfeng, Anle) and a town (Chengguan) were selected from the mountainous region with high incidence of visceral leishmaniasis in Nanping County, northern Sichuan for carrying out an extensive experiment of medicated bathing of domestic dogs, where there were 13 new infected cases in the year of 1991 before the experiment. During the sandfly season in 1992, two rounds of medicated bathing of dogs were conducted, the drug concentration used was 50 ppm. From September 1992 to August 1993, the number of new infected cases was 11 in the above mentioned three villages and a town. Another two rounds of medicated bathing of dogs had been conducted during the sandfly season in 1993. The results show that there was no new infection from September 1993 to October 1994 in the three villages and a town, indicating that through two years' consecutive extensive medicated bathing of dogs in the endemic areas, canine visceral leishmaniasis transmission had been significantly interrupted. The authors consider that in the mountainous region of southern Gansu and northern Sichuan where it has been difficult to treat dogs, it might be more practical to use deltamethrin bathing of dogs for interrupting the transmission of canine visceral leishmaniasis.

Animals↗