Exact solutions of the Schrödinger equation for some quantum-mechanical many-body systems.
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Journal Article↗
Biomedical subjects
R Zhang
Publications and source records attributed to R Zhang.
The time of administration of 3'-azido-3'-deoxythymidine (AZT) determines its host toxicity with possible relevance to AZT chemotherapy.
3'-Azido-3'-deoxythymidine (AZT) is the drug most widely used in the treatment of AIDS. Its major drug-related toxicity is bone marrow suppression, which limits the dose of AZT that can be used. It is essential that AZT be phosphorylated for antiviral effect. We have recently demonstrated that thymidine kinase (TK), the initial enzyme in AZT anabolism, follows a circadian pattern in rat bone marrow. The present study was undertaken to determine whether AZT toxicity is related to the time of its administration and whether the variation in toxicity is correlated with the circadian variation in TK activity. Male Sprague-Dawley rats were housed under standardized conditions of light and dark (lights on 0600 to 1800 and lights off 1800 to 0600) for 4 weeks. The animals were randomly divided into seven groups; six groups were administered AZT by intraperitoneal injection at the same dose of 750 mg/kg of body weight at various times (0400, 0800, 1200, 1600, 2000, and 2400), and one group was used as a control. AZT-related toxic effects, including bone marrow toxicity, differed significantly among the treatment groups, depending on the time of AZT administration (by analysis of variance and Cosinor analysis, P < 0.001). The least toxicity was observed in rats receiving AZT at 1600 (10 h after light onset [10 HALO], in late sleep span) and the greatest toxicity was observed in those injected at 0400 (22 HALO, in late activity span). To verify these results, we administered AZT by intraperitoneal injection at an approximately 50% lethal dose (1,500 mg/kg) to two groups of rats, one at 1200 (6 HALO, in the middle of the sleep span) and the other at 2400 (18 HALO, in the middle of the activity span). AZT lethality was significantly higher in rats receiving AZT at 2400 (18 HALO, in the middle of the activity span). Further statistical analysis demonstrated that the variation in AZT toxicity was correlated with the circadian variation in TK activity in bone marrow of the same species (peak activity at 0400 [22 HALO, in late activity span] and trough activity at 1600 [10 HALO, in late sleep span]), suggesting that the circadian variation in TK activity may be the biochemical basis for the observed circadian variation in AZT toxicity. These results may be useful in the design of improved AZT chemotherapeutic regimens.
Analysis of Variance↗
Tissue-specific expression of mRNA encoding rat kidney water channel CHIP28k by in situ hybridization.
The tissue distribution of mRNA encoding rat kidney water channel CHIP28k was determined by in situ hybridization. cDNA encoding rat kidney CHIP28k was isolated by homology to human erythrocyte CHIP28 (G. M. Preston and P. Agre. Proc. Natl. Acad. Sci. USA 88: 11110-11114, 1991) and used to construct 155-base 35S-labeled cRNA sense and antisense probes corresponding to base pair 7-162. Fixed and frozen tissues were cut in 6- to 12- microns sections, hybridized with probes at 55 degrees C for 16 h, and exposed for 5-9 days. In renal cortex, CHIP28k mRNA was detected intensely on proximal tubule epithelial cells but not in glomeruli or collecting duct. Hybridization to proximal tubule was strongest in deep renal cortex. In no study was there significant hybridization of sense cRNA probe. In renal papilla, CHIP28k mRNA was detected in only a fraction of tubules corresponding to thin limbs of Henle. Hybridization in spleen was observed in red splenic pulp containing erythroid precursors but not in white pulp. In colon, there was selective hybridization in crypt epithelial cells but not in villus epithelial cells or nonepithelial structures. In lung, hybridization was observed in alveolar epithelial cells. In eye, there was selective hybridization in corneal endothelium and ciliary body. No hybridization was observed in any cell types in liver. Northern analysis revealed a 2.8-kilobase mRNA encoding CHIP28k in kidney cortex and papilla but not in brain, skeletal muscle, and liver. These results indicate a wide and highly selective tissue distribution of mRNA encoding the CHIP28k water channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Phase I trial of low-dose, prolonged continuous infusion fluorouracil plus interferon-alfa: evidence for enhanced fluorouracil toxicity without pharmacokinetic perturbation.
PURPOSE: To determine the maximum-tolerable dose (MTD) of fluorouracil (5-FU) administered as a low-dose, prolonged continuous intravenous infusion (PCI) plus interferon-alfa (IFN-alpha) that would permit treatment for at least 28 consecutive days, and to determine the effect of IFN-alpha on 5-FU pharmacokinetics. PATIENTS AND METHODS: Twenty-six assessable patients with advanced cancer received low-dose PCI 5-FU (150, 200, 250, and 300 mg/m2/d) plus IFN-alpha, 5 x 10(6) IU/m2 administered subcutaneously (SC) at hour 48 of the 5-FU infusion, then thrice weekly thereafter in cohorts of at least three patients. Treatment continued until treatment-limiting toxicity (TLT) developed, such as mucositis, diarrhea, or fatigue. Escalation to the next 5-FU dose level occurred if none of three or zero to two of six patients developed TLT before day 28. Quantitation of plasma 5-FU concentration by high-performance liquid chromatography was performed in 15 patients. Data were standardized using the Cosinor method and compared before and after IFN-alpha administration using the paired t test. RESULTS: The mean number of days of continuous 5-FU therapy for patients receiving 150, 200, 250, and 300 mg/m2/d of 5-FU plus IFN alfa-2a (IFN-alpha 2a) was 75, 54, 37, and 22 days, respectively. The MTD of PCI 5-FU by our criteria that could be combined with IFN-alpha was 250 mg/m2/d. Comparison of the standardized pharmacokinetic data showed no significant effect of IFN-alpha on plasma 5-FU concentration, and no alteration of the normal circadian variation in plasma 5-FU concentration that was evident before IFN-alpha administration. Objective response occurred in patients with adenocarcinoma of the pancreas (n = 3), kidney (n = 2), and lung (n = 1). CONCLUSION: IFN-alpha substantially enhanced the gastrointestinal toxicity of low-dose PCI 5-FU without affecting 5-FU pharmacokinetics, contrary to previous reports using alternative 5-FU schedules in which IFN-alpha-related enhancement of 5-FU toxicity was attributable to reduced 5-FU clearance. Our findings suggest that under certain conditions, mechanisms other than altered 5-FU pharmacokinetics may be responsible for the ability of IFN-alpha to enhance the toxic effects of 5-FU.
Adult↗
[The pain components of somatosensory evoked potentials induced by median nerve stimulation P200-N300].
The pain components of somatosensory evoked potentials (SEPs) of induced by median nerve stimulation were studied with the way of blocking bloodstream of arm in 12 normal adults. The SEPs following the painful stimuli (0.1 msec. square wave pulse) of the right wrist were recorded from the left parietal (C3') and frontal (F3) scalp with earlobe reference electrode. The pressure of 40 mmHg above the arterial pressure was given to the right upper arm by sphygmomanometer. The result showed that the P200-N300 components (latency 234 +/- 13 msec. and 308 +/- 23 msec.) of the SEPs persisted and the others disappeared when tactile sensation disappeared but pain existed. The morphology of P200-N300 from F3 was same to that from C3'. It suggested the P200-N300 were the pain potentials of median nerve SEPs.
Adult↗
[A survey on enteroviruses-carrying status among healthy population in Changle and Wucheng counties of Shandong Province. Shandong Collaborative Group of Poliomyelitis].
Four-hundred and fourty-six faecal specimens sampled from healthy carriers between 0 and more than 20 year-old age groups in Changle and Wucheng counties of Shandong Province were collected from June to Sept. of 1991. From them, 142 (31.84%) isolates of enteroviruses were obtained. There was no significant difference in the enteroviruses isolation rate between Changle and Wucheng. No poliovirus was isolated. Among other enterovirus isolates, 85 were echoviruses, 6 coxsackieviruses, 9 enterovirus type 70 and 2 enterovirus type 71. Other 40 isolates were positive for cytopathogenic effect (CPE) in cell culture, but they could not be identified by antisera to poliovirus and enteroviruses. The results showed that the infection by non-polio enteroviruses which could cause polio-like paralysis should be paid attention in the poliomyelitis eradication program.
Adolescent↗
[The stimulatory effect of dorsal vagal complex injection of pentagastrin on gastric motility in rats].
Changes in antral motility induced by pentagastrin (G5) microinjected into the dorsal vagal complex (DVC) were investigated in fasting conscious rats. Antral motility was monitored by using chronically implanted force transducer sutured to the antrum. DVC injection of G5 markedly stimulated the amplitude of gastric contraction in a dose-dependent manner. The effect, being rapid in onset and long lasting, could not be mimicked by intravenous administration of G5 but could be markedly inhibited by microinjection of antigastrin serum into DVC. Atropine (100 micrograms.kg-1.h-1) and vagotomy could also abolish the G5 induced antral motility. No significant changes in plasma motilin were observed in portal venous blood after administration of G5 in DVC. These results suggested that DVC is an important site of action for G5 induced stimulation of gastric contraction as mediated by vagal cholinergic pathway.
Animals↗
[Studies on gap junction formation and junctional communication between cultured endothelial cells and smooth muscle cells].
Gap junction (GJ) between two contacted cells is the structural basis of intercellular communication. Gap junction transfer plays an important role in regulation of cell proliferation. Cultured endothelial cells (EC) and smooth muscle cells (SMC) were injected with fluorescein Lucifer Yellow by iontophoretic injection, and examined under fluorescein microscope. We have demonstrated that there existed homologous and heterologous GJ and contact mediated dye transfer between cultured EC and SMC. LDL and insulin which promote SMC proliferation may inhibit the junctional communication between SMC and EC. Tumor promoter TPA induced almost complete inhibition of junctional communication between EC and SMC. The results indicate that normally regulative signals of metabolism and growth are transferred between EC and SMC via junctional communication to maintain the vessel wall homeostasis. High dosage LDL and insulin may keep SMC away from normal growth control and induce their proliferation by means of inhibiting junctional communication. It may be one of important mechanisms of atherogenesis.
Animals↗
Indirect photometric detection of polyamines in biological samples separated by high-performance capillary electrophoresis.
A rapid separation of polyamines and some related amino acids in cultured tumor cells by high-performance capillary zone electrophoresis with indirect photometric detection is demonstrated. 60 cm x 75 microns I.D. fused-silica capillary was used for the separation and quinine sulfate was used as a background electrolyte (BGE). Several polyamines (putrescine, spermidine and spermine), amino acids (lysine, arginine, histidine) and simple cations (K+, Na+) were easily separated in less than 10 min. Using the indirect photometric detection method, femtomole amounts of polyamines extracted from the tumor cells were detected from nanoliter injection volumes, and the signal response was linear over two orders of magnitude.
Animals↗
Purification and characterization of dihydropyrimidine dehydrogenase from human liver.
Although dihydropyrimidine dehydrogenase has been purified to varying degrees from several species, very little is known about the human enzyme. The importance of this enzyme has recently been shown with cancer chemotherapy, particularly in patients with genetic deficiency of this enzyme. In the present study, this enzyme was purified 7800-fold to homogeneity from human liver by introducing several novel methods including chromatofocusing, HPLC gel filtration, reversed-phase HPLC for the enzyme assay. Purified human enzyme has a molecular mass of 210 +/- 5 kDa and appears to be composed of two subunits. The apparent pI is pH 4.6 (+/- 0.2). The human enzyme contains approximately four flavin nucleotide molecules (two each of FAD and FMN) and 33 iron atoms per molecule of enzyme. Kinetic studies with uracil, thymine, 5-fluorouracil, and NADPH were carried out. Amino acid composition and the N-terminal amino acid sequence of this enzyme were reported. A rabbit polyclonal antibody was raised and shown to be specific for the human liver enzyme. In conclusion, in the present manuscript, we report not only a novel procedure for purification of dihydropyrimidine dehydrogenase from human liver but also new data on its properties compared to other species, which will provide a basis for further biochemical and molecular studies of this enzyme.
Animals↗
Two mRNAs are transcribed from the human gene for choline acetyltransferase.
The product of the choline acetyltransferase (ChAT) gene is the enzyme that synthesizes the neurotransmitter acetylcholine. A 14.4-kb portion of the human ChAT gene contains 7 exons, which are estimated to comprise approximately one-third of the human protein coding sequence by comparison with porcine ChAT mRNA. Two of the exons were used to identify polyadenylated human ChAT gene transcripts on Northern blots. An exon with 84% identity to the region of porcine ChAT mRNA that codes for the amino terminus of the corresponding protein detected 6,000- and 2,300-nucleotide mRNAs in RNA isolated from human CHP134 neuroblastoma cells. Only the 2,300-nucleotide mRNA was detected by a second probe containing an exon with 96% identity to porcine ChAT mRNA in the domain that encodes amino acids 204-263 of the predicted porcine ChAT protein. Further evidence that two species of human mRNA are produced from the human ChAT gene was obtained from nuclease protection assays using an antisense RNA probe prepared from a human ChAT cDNA clone. Total RNA isolated from either CHP134 cells or adult human nucleus basalis protected 525- and 400-nucleotide fragments of this probe, confirming the presence of two species of RNA that differ by the inclusion of an internal exon. cDNA clones of each of these transcripts have been isolated. Their sequences suggest that the 2,300-nucleotide mRNA encodes enzymatically active human ChAT, while translation of the 6,000-nucleotide mRNA would be terminated prematurely by a shift in the reading frame. These results indicate that a complex pattern of transcription produces two mRNAs with different coding potentials from the human ChAT gene.
Blotting, Northern↗
Gene structure and multiple mRNA species of Drosophila melanogaster aldolase generating three isozymes with different enzymatic properties.
Genomic clones encoding the Drosophila aldolase gene were isolated and the organization of the gene was determined. The protein-coding region spanning nearly 3.5 kb consists of five coding exons (exon 2, 3, 4 alpha, 4 beta, and 4 gamma). The insect exon 2 corresponds to exons 2 to 7 of vertebrate aldolase genes and thus appears to have been formed by the fusion of these 6 exons into a single exon during evolution. The Drosophila aldolase gene is predicted to generate mRNAs for three isozymes (alpha-, beta-, and gamma-types) from the primary transcripts by alternative usage of the final three exons. The reverse transcriptase-PCR assay revealed the occurrence of mRNAs for the three isozymic forms at different developmental stages, and tissue-specific expression was also found to occur in adult flies. In addition to the usual type mRNA species for the alpha-, beta-, and gamma-isozymes, two novel forms of mRNAs, alpha beta- and beta gamma-type mRNAs, were detected tissue-specifically in adult flies, although their functions are unpredictable. The alpha beta-mRNA is an alpha-type mRNA in which exon 4 beta remains unspliced, while the beta gamma-mRNA is a beta-type mRNA with the exon 4 gamma remaining unspliced. Recombinant enzymes expressed in Escherichia coli were all active and exhibited different enzymatic properties.
Amino Acid Sequence↗
Differential intestinal deconjugation of taurine and glycine bile acid N-acyl amidates in rats.
Mechanisms responsible for the difference in the relative amounts of taurine- and glycine-conjugated bile acid N-acyl amidates (Tau/Gly ratio) are not fully understood. In the present study, the stability of taurine- and glycine-conjugated bile acid N-acyl amidates during intestinal transit and absorption was examined to investigate the contribution of intestinal deconjugation to the Tau/Gly ratio in rat bile. Radiolabeled chenodeoxycholic acid (CDC) and its N-acyl amidates with glycine (CDC-Gly) or taurine (CDC-Tau) were introduced into the lumen of the upper small intestine in the biliary fistula rats, and radioactive metabolites in bile, blood, urine, and tissues were identified and quantitated by high-performance liquid chromatography. Results indicated that 1) extensive deconjugation of CDC-Gly occurs during intestinal absorption; 2) CDC-Tau is recovered in bile largely intact; and 3) newly synthesized CDC-Tau and CDC-Gly are formed in a ratio of less than 2:1 after administration of [14C]-CDC. In summary, the present study demonstrates that resistance of taurine-conjugated bile acid N-acyl amidates to hydrolysis in the intestine, rather than a difference in synthesis of taurine- and glycine-conjugated N-acyl amidates in liver, may account for the high Tau/Gly ratio in rat bile.
Animals↗
Electronystagmographic features in some peripheral and central vestibular disorders: application of multiple discriminant analysis of electronystagmographic parameters.
In routine clinical electronystagmographic (ENG) tests (postrotatory, optokinetic, caloric and tracking tests), eye movement signals were analyzed and a multiple discriminant analysis was carried out with the aid of a microcomputer. Six parameters were selected and, based on these, two functions for discriminating between peripheral and central disorders were established. Discrimination between 35 patients with peripheral lesions and 15 patients with central lesions was made with a correct classification rate of 97.1 and 86.7%, respectively. These rates are significantly higher than that of any single ENG test analysis. Our results indicate that the clinical application of ENG can be improved by searching for more sensitive ENG parameters and adopting the comprehensive analysis approach.
Adult↗
Indonesian medicinal plants. II. Chemical structures of Pongapinones A and B, two new phenylpropanoids from the bark of Pongamia pinnata (Papilionaceae).
Two new phenylpropanoids named pongapinone A (1) and pongapinone B (2) were isolated from the bark of Pongamia pinnata (Papilionaceae), an Indonesian medicinal plant, and their chemical structures have been elucidated on the basis of their physicochemical properties. Pongapinone A (1) was found to inhibit interleukin-1 production.
Chromones↗
Indonesia medicinal plants. III. On the constituents of the bark of Fagara rhetza (Rutaceae). (1): Alkaloids, phenylpropanoids, and acid amide.
Two new phenylpropanoids, named O-geranylsinapyl alcohol (1) and O-geranylconiferyl alcohol (2), and a new acid amide, named hazeleamide (3), were isolated from the bark of Fagara rhetza (Rutaceae), an Indonesian medicinal plant from Flores Island, Indonesia. The chemical structures of 1, 2, and 3 have been elucidated on the basis of their chemical and physicochemical properties. Among the three new compounds, hazeleamide (3) was found to show a pungent taste and to exert a moderate antimalarial activity in an in vitro test system.
Alkaloids↗
Use of the scan statistic to detect temporal clustering of poisonings.
The purpose of this study is to explore the use of the scan test to detect temporal clustering of poison control center data. We applied the scan test to a computerized data set consisting of all cases of carbon monoxide poisoning reported to our Poison Control Center in 1988. Using a time window of three days, the scan test identified three statistically significant temporal clusters. A review of case and climatologic data revealed that two of the clusters were due to family outbreaks and one was due to a sudden cold spell. We conclude that the scan test is a potentially useful surveillance tool which can be easily applied to poison control center data.
Carbon Monoxide Poisoning↗
Interim report of Sino-Monica-Beijing for the years 1985-1989.
Interim results of Sino-Monica-Beijing for the 5 year period 1985-1989 are reported. The cardiovascular disease (CVD) risk factors increased between the surveys carried out in 1984-1985 and 1988-1989, especially blood cholesterol and body mass index.
Adult↗