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Biomedical subjects

M Qian

Publications and source records attributed to M Qian.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Audiological findings of the aging across the urban and rural of Suzhou].

OBJECTIVE: To determine the epidemiological characteristics of old people's hearing. METHOD: Questionnaires, physical examination, audiometry and bio-chemical tests were performed on the elders above 60 years old in part of the urban and rural area of Suzhou with random sample survey. RESULT: A total of 1,040 individuals was investigated, among which 505 were from urban, and 535 were from rural. 33 of 505 senior citizen (6.53%) were nososacusis, 282 (55.84%) were presbycusis and 21 (4.16%) were noise-induced deafness; In the rural area, 35 of 535 (6.54%) were nososacusis, 232 (43.36%) were presbycusis, and 4 (0.75%) were noise deafness. There was significant difference of the incidence of presbycusis between urban and rural. The audiometric thresholds chart manifested that the threshold elevated with age increasing especially in high-frequency. CONCLUSION: The etiology of hearing loss of elders was mainly due to presbycusis. The higher incidence of psychotic disorder in urban probably caused a correspondingly higher incidence of presbycusis. So the prevention and cure of some age-induced diseased (e.g. hypertension, arteriosclerosis and diabetes) may be helpful to release and improve presbycusis.

Aged↗
PubMed2001

[Cytotoxic effect of Acanthamoeba trophozoite on HeLa cells].

OBJECTIVE: To investigate the cytotoxic effect(CTE) on human cervix cancer HeLa cells induced by five strains of pathogenic free-living Acanthamoeba. METHODS: The cytotoxic effect of five isolates of Acanthamoeba on HeLa cells was investigated by light microscopy and MTT method. RESULTS: The photomicrographs of HeLa cells showed a sequence of cardinal morphological features of apoptosis when HeLa cells were exposed to Acanthamoeba in a time-dependent manner at a ratio of 1:1 for 12 h. MTT method showed more than 50% of tumor cells underwent cytolysis following exposure to A. lugdunensis trophozoites, and only 18% of cells treated with A. polyphaga underwent CTE. The CTE produced by A. lugdunensis and A. quina trophozoites was more rapid than the others, beginning as early as 6 h after coincubation and resulting in cytolysis by 72 h. CONCLUSION: These five strains of Acanthamoeba exhibit cytotoxic effects of varying degrees on HeLa cells, inducing apoptosis.

Acanthamoeba↗
PubMed2000

Evidence that MK-801 stimulates intraoral intake by acting on hepatic afferents.

Satiety signals from the gastrointestinal tract travel via vagal afferents to the nucleus of the solitary tract (NTS) in the brain stem, the first central relay in a neural network which controls food intake. The non-competitive NMDA antagonist MK-801 facilitates food intake in rats by acting on the NTS. Here we report that hepatic portal vein infusion of MK-801 (25 or 50 microg/kg) increases intake of an intraorally infused 1 M solution of sucrose (by 113 +/- 9 and 132 +/- 11%, respectively) and that this effect is prevented by hepatic vagotomy. By contrast, jugular vein infusion of MK-801 fails to increase sucrose intake but induces forward locomotion, indicating activation of a central mechanism. These data suggest that MK-801 can stimulate food intake by acting peripherally on hepatic vagal afferents.

Animals↗
PubMed2000

Pumped biochemical reactions, nonequilibrium circulation, and stochastic resonance.

Based on a master equation formalism for mesoscopic, unimolecular biochemical reactions, we show the periodic oscillation arising from severe nonequilibrium pumping is intimately related to the periodic motion in recently studied stochastic resonance (SR). The white noise in SR is naturally identified with the temperature in the biochemical reactions; the drift in the SR is associated with the circular flux in nonequilibrium steady state (NESS). As in SR, an optimal temperature for biochemical oscillation is shown to exist. A unifying framework for Hill's theory of NESS and the SR without periodic forcing is presented. The new formalism provides an analytically solvable model for SR.

Biological Clocks↗
PubMed2000

Glycochelates and the etiology of diabetic peripheral neuropathy.

People with diabetes are prone to develop peripheral vascular and nerve abnormalities which, in extreme cases, can lead to limb amputations. Although numerous theories have been advanced for these complications, no firm explanation is yet available. Recently, evidence has appeared suggesting that these vascular and nerve abnormalities may involve transition metals; administration of chelators such as desferrioxamine has been shown to prevent or actually reverse slowed peripheral nerve conduction and neuronal blood flow, as well as impaired endothelium-dependent arterial relaxation. Here, we argue that (i) the heavily glycated proteins known to accumulate in people with diabetes gain an increased affinity for transition metals such as iron and copper, (ii) as a result, proteins such as elastin and collagen within the arterial wall-which are known to be particularly heavily glycosylated in diabetes-may accumulate bound metal, especially copper, (iii) the bound metal causes the catalytic destruction of endothelium derived relaxing factor (nitric oxide or a derivative thereof), thereby engendering a state of chronic vasoconstriction. The resulting impairment of blood flow to peripheral nerves restricts the delivery of oxygen and nutrients and, in extremis, nerve death eventuates. If this hypothesis is proved correct, there are important implications for the development of novel pharmaceuticals for the treatment of diabetic peripheral neuropathy.

Animals↗
PubMed2000

Characterization and gene structure of a novel retinoblastoma-protein-associated protein similar to the transcription regulator TFII-I.

Retinoblastoma protein (Rb) is an important regulator of vertebrate cell cycle and development. It functions through a direct interaction with protein factors involved in cell cycle progression and differentiation. In the present study we characterized a novel Rb-associated protein, Cream1, which bound to Rb specifically through a C-terminal region. Cream1 contained 959 amino acid residues and migrated as a protein of approx. 120 kDa on SDS/PAGE. It was a widely expressed nuclear protein with a nuclear localization signal resembling that of the large T antigen of simian virus 40. Its primary sequence was characteristic of five direct repeats that were similar to, but distinct from, those of TFII-I, a multifunctional transcription regulator. Three additional regions were also highly conserved in both proteins. Cream1 exhibited an activation activity that was attributed to its N-terminal portion when assayed in yeast. Its relationship with the muscle-enhancer-binding protein MusTRD1 further suggests a role in regulating gene expression. The structural gene, CREAM1, contained 27 exons and spanned more than 150 kb. It was located at human chromosome 7q11.23 in a region deleted for Williams' syndrome, a neurodevelopmental disease with multisystem abnormalities, implying its involvement in certain disorders. Taken together, our results suggest that Cream1 might serve as a positive transcription regulator under the control of Rb.

Amino Acid Sequence↗
PubMed2000

Direct plasma sample injection in multiple-component LC-MS-MS assays for high-throughput pharmacokinetic screening.

The simultaneous dosing of numerous compounds followed by multiple-component analysis using LC-MS-MS (the N-in-1 approach) has significantly improved the throughput of the drug-screening process. However, plasma samples still need to be extracted before LC-MS-MS analysis, which frequently limits the throughput of the assay. In this work, a high-throughput on-line extraction technique has been developed for multiple-component LC-MS-MS assays using a high-flow column-switching technique. In N-in-1 LC-MS-MS assays, high sensitivity is required since the dose level is generally reduced to minimize drug-drug interactions. In addition, good chromatographic separation is essential to minimize interference and suppression effects. The direct plasma sample injection method developed in this work has successfully met the two requirements for multiple-component LC-MS-MS assays in high-throughput pharmacokinetic screening. Plasma samples containing a large number of potential drug candidates were directly injected onto an extraction column operated under a flow rate sufficiently high to exhibit a turbulent-flow profile. The extracted analytes were then eluted onto an analytical column via column switching for LC-MS-MS analysis. The use of turbulent flow resulted in a faster and more rugged extraction with reduced carryover compared with results obtained under laminar-flow conditions. Meanwhile, the use of a column-switching method maintained the chromatographic resolving power and high sensitivity of the LC-MS-MS assay. Separation efficiency, dynamic range, accuracy, and precision comparable with those of solid-phase extraction have been achieved with the turbulent-flow column-switching technique. As a result, this technique has been successfully and routinely used for high-throughput pharmacokinetic screening.

Animals↗
PubMed2000

Distribution of ferritin and redox-active transition metals in normal and cataractous human lenses.

Previous studies have shown that lenticular levels of Fe and Cu are elevated in age-related cataract. However, it is not known if these metals are present in a state that is permissive for redox reactions that may lead to the formation of free radicals. In addition, there is little data available concerning the concentration and lenticular distribution of ferritin, the major intracellular Fe-sequestering protein, in the lens. The aim of the present work was therefore to determine the distribution of ferritin and the redox-availability of Fe and Cu in healthy and cataractous lenses. Lens ferritin distribution was assessed by ELISA and immunohistochemistry. A modified ELISA detected ferritin in an 'insoluble' lens protein fraction. Ferritin levels were not significantly different in the cortex vs nucleus of healthy lenses. In contrast, ferritin levels in the cataractous lens nuclei appeared to be 70% lower compared to the cortex. This was at least partially due to the presence of ferritin within an insoluble protein fraction of the homogenized lenses. In normal lenses, ferritin staining was most intense in the epithelium, with diffuse staining observed throughout the cortex and nucleus. The redox-availability of lenticular metals was determined using: (1) autometallography; (2) Ferene-S as a chromogenic Fe chelator; and (3) NO release from nitrosocysteine to probe for redox-active Cu. The autometallography studies showed that the cataractous lenses stained more heavily for redox-active metals in both the nucleus and cortex when compared to age-matched control lenses. Chelatable Fe was detected in homogenized control lenses after incubation with Ferene-S, with almost three-fold higher levels detected in the cataractous lenses on average. The Cu-catalysed liberation of NO from added nitrosocysteine was not demonstrated in any lens sample. When exogenous Cu (50 n M) was added to the lenses, it was rapidly chelated. The cataractous samples were approximately twice as effective at redox-inactivation of added Cu. These studies provide evidence that a chelatable pool of potentially redox-active Fe is present at increased concentrations in human cataractous lenses. In contrast, it seems that lenticular Cu may not be readily available for participation in redox reactions.

Aged↗
PubMed2000

Stochastic resonance on a circle without excitation: physical investigation and peak frequency formula

In this article the existence of stochastic resonance (SR) without external force in a simplified circular system for different values of the control parameter b is considered. The average power spectra are calculated as well as the signal-to-noise ratio as a measure for stochastic resonance. It is shown that in the monostable and semistable (b<1 and b=1) cases coherent oscillations occur and SR exists. For the case b>1, the system is oscillatory and noise plays only a destructive role; therefore no SR occurs. The rotation number of the system is calculated and compared to the peak frequency of the power spectrum. Although the coincidence in the noisy case is not as good as that in the deterministic case, we can derive an empirical formula between the peak frequency of the power spectrum and the rotation number of the system, which is in good agreement with results of numerical simulations.

Journal Article↗
PubMed2000

Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with refractory solid malignancies.

Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and antitumor activity in murine tumor models. Putative mechanisms of action include activation of the transforming growth factor beta pathway and/or inhibition of p21ras signaling, leading to differentiation or apoptosis. In this Phase I trial, 17 patients took POH p.o. three times daily for 14 days of each 28-day cycle. The starting dose of POH was 1600 mg/m2/dose, with escalations to 2100 and 2800 mg/m2/dose in subsequent cohorts. Chronic nausea and fatigue were dose-limiting toxic effects at 2800 mg/m2. Grade 1-2 hypokalemia was common at 2100 and 2800 mg/m2. Although POH could not be detected in plasma, two of its metabolites, dihydroperillic acid (DHPA) and perillic acid (PA), were measured in plasma and urine on days 1 and 15 after the first and last doses of POH, respectively. Both area under the concentration versus time curve and peak plasma concentration (Cmax) values increased with dose and exhibited high intersubject variability. Day 15 DHPA Cmax values ranged from a mean +/- SD of 22.6+/-12 microM at 1600 mg/m2/dose to 42.4+/-15.24 microM at 2800 mg/m2/dose. Corresponding mean +/- SD Cmax values for PA were 433.2+/-245.8 and 774.1+/-439.6 microM. One patient treated at the 2800 mg/m2/dose had markedly prolonged plasma levels of both PA and DHPA and developed grade 3 mucositis. POH treatment did not consistently alter the expression of p21ras, rap1, or rhoA in peripheral blood mononuclear cells obtained from patients treated at the highest dose level. The metabolites PA and DHPA did not change expression or isoprenylation of p21ras in MCF-7 breast or DU145 prostate carcinoma cells at concentrations that exceeded those achieved in patient plasma after POH treatment. We conclude that POH at 1600-2100 mg/m2 p.o. three times daily is well tolerated on a 14-day on/14-day off dosing schedule. Inhibition of p21ras function in humans is not likely to occur after POH administration at safe doses of the present oral formulation.

Administration, Oral↗
PubMed2000

Risk factors for development of diabetes mellitus in women with a history of gestational diabetes mellitus.

OBJECTIVE: To determine whether diabetes recurs in their later life when women have a history of gestational diabetes mellitus (GDM) or abnormal glucose tolerance test (impaired glucose tolerance, IGT). METHODS: Three groups of women were investigated at 5-10 years postpartum. GDM group (n = 45) had been diagnosed as having GDM in their previous pregnancy. IGT group (n = 31) had a history of abnormal glucose tolerance test during previous pregnancy. Normal control group (n = 39) was normal previous pregnant population. Their previous obstetric and medical histories were thoroughly reviewed. Fasting plasma glucose (FPG) and oral glucose (75 g) tolerance test (OGTT) were repeated in all women. RESULTS: Diabetes mellitus (DM) was diagnosed in 33.3% of patients in the GDM group, while in 9.7% in the IGT group and in 2.6% in the normal control group. Incidence of recurring DM in later life was significant higher in the GDM group (P = 0.017). When one or more blood glucose values exceeding WHO criteria for diagnosis of diabetes in their previous pregnancy, the incidence of DM in later life was 60% (3/5, including GDM in women having four abnormal OGTT values), 41.7% (5/12) in women having three, 25% (7/28) in women having two and 9.7% (3/31) in women having one. The women with DM, also with a history of GDM and abnormal OGTT in previous pregnancy, tends to have a high pregnant body mass index (BMI > 25 kg/m2). CONCLUSION: The women suffering from GDM during previous pregnancy have a high risk of recurrence DM. Two or more abnormal OGTT values during pregnancy, blood glucose level exceeding the maximal values at 1 and 2 hours after oral glucose loading and high pregnant BMI are concluded to be useful factors in predicting the recurring DM in their later life.

Adult↗
PubMed2000

[A preliminary meta-analysis of 36 studies on impairment of intelligence development induced by iodine deficiency].

OBJECTIVES: Since 1980 s', numerous studies on intelligence quotient (IQ) have documented, in the areas prevalent with severe, moderate and even mild iodine deficiency, which is a risk factor for retardation in mental development there. It was purposed for this paper to quantify the relationship between iodine deficiency and mental development in children and to explore the etiological role of iodine deficiency in mental retardation and the protective effects on children's intelligence of iodine supplementation. METHODS: A total of 59 independent investigations published during 1980 and 1998 were selected for meta-analysis, including 20 studies on intelligence determined by Raven's Test and 39 by China Benit Scale. RESULTS: Homogeneity test showed that there was no significant difference in baseline features between two groups (P > 0.05). The hypothesis testing showed that the homogeneity of each study group was obviously statistically significant (P > 0.05). The results demonstrated that IQ in children at risk for iodine deficiency showed a marked drop by 8.94 points with Raven's Test and by 10.80 points with China Binet Scale, respectively, with an average drop of 10 points. Substantial evidence now available has showed that mental retardation can be prevented by effective correction of iodine deficiency through iodine supplement either iodized salt or iodized oil, which is confirmed by an obvious increase in 11.5 points of IQ in average, and in 11.85 by Raven's Test and 11.64 by China Binet Scale, respectively. CONCLUSIONS: Iodine nutrition plays an important and positive role in brain development. Iodine deficiency leads to loss of 10 points of IQ and 11.5 points can be gained for children in the iodine deficiency areas after significant iodine supplement.

Adolescent↗
PubMed2000

[Insulin-like growth factor-I(IGF-I), and its binding protein-3 (IGFBP-3) correlated with fetal development].

OBJECTIVE: To study the relations between IGF-I, IGFBP-3 and human fetal growth. METHODS: The blood samples of maternal serum (MS) and umbilical cord serum (UCS) from 81 cases with singleton term pregnancy including 38 cases of normal pregnancy (NP), 20 cases of gestational diabetic mellitus (GDM), 23 cases of macrosomia of non-diabetic pregnancy (MNDP) were examined for IGF-I and IGFBP-3 levels by immunoassay kit from DSL, USA. RESULTS: IGF-I in MS of NP and MNDP showed a positive correlation with birth weight (BW) (r = 0.653 and r = 0.640 respectively, both P < 0.01). IGF-I of MS in MNDP was higher than that in NP (P < 0.05). IGF-I of MS and UCS in GDM were higher than that in NP (P < 0.05). IGF-I and IGFBP-3 of UCS in these three groups were significantly lower than that of MS (P < 0.001). CONCLUSION: Detection of IGF-I in MS can assess fetal intra-uterus growth, birth weight and has certain value of predicting macrosomia. IGF-I and IGFBP-3 play important roles for human fetal growth.

Adult↗
PubMed1999

Proton transfer to residues of basic pK(a) during catalysis by carbonic anhydrase.

The maximal velocity in the hydration of CO(2) catalyzed by the carbonic anhydrases in well-buffered solutions is limited by an intramolecular proton transfer from zinc-bound water to acceptor groups of the enzyme and hence to buffer in solution. Stopped-flow spectrophotometry was used to accumulate evidence that this maximal velocity is affected by residues of basic pK(a), near 8 to above 9, in catalysis of the hydration of CO(2) by carbonic anhydrases III, IV, V, and VII. A mutant of carbonic anhydrase II containing the replacement His-64-->Ala, which removes the prominent histidine proton shuttle (with pK(a) near 7), allows better observation of these basic groups. We suggest this feature of catalysis is general for the human and animal carbonic anhydrases and is due to residues of basic pK(a), predominantly lysines and tyrosines more distant from the zinc than His-64, that act as proton acceptors. These groups supplement the well-studied proton transfer from zinc-bound water to His-64 in the most efficient of the carbonic anhydrases, isozymes II, IV, and VII.

Animals↗
PubMed1999

Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing.

Three human glutaminase (hGA) isoforms were identified, two of which represent isoforms previously unidentified in any species. One isoform contains an open reading frame with high homology with the rat kidney-type glutaminase, suggesting that this isoform represents the human kidney-type glutaminase, hKGA. A second isoform, termed hGAC, contains an open reading frame that matches hKGA except for a unique COOH-terminal amino acid sequence. In addition, a third human glutaminase isoform was identified from a computer search and on further analysis was found to represent an additional unique isoform, hGAM. hKGA is expressed predominantly in brain and kidney but not in liver, hGAC is expressed principally in cardiac muscle and pancreas but not in liver or brain, and hGAM is expressed solely in cardiac and skeletal muscle. hGAC is the predominant isoform expressed by a human breast cancer cell line that exhibits a high rate of glutamine utilization and glutaminase activity. Genomic Southern analysis as well as isolation and analysis of five glutaminase genomic clones suggested that all three hGA isoforms originate from the same locus and therefore represent mRNA species that are produced by tissue-specific alternative splicing of a single pre-mRNA. Furthermore, an RT-PCR assay was developed that can be used to easily differentiate between hKGA and hGAC mRNA species.

Alternative Splicing↗
PubMed1999

Impact of mutations within the putative Ca2+-binding lumenal interhelical a-b loop of the photosystem II D1 protein on the kinetics of photoactivation and H2O-oxidation in Synechocystis sp. PCC6803.

Mutations D1-D59N and D1-D61E in the putative Ca2+-binding lumenal interhelical a-b loop of the photosystem II (PSII) D1 protein [Chu, H. A., Nguyen, A. P., and Debus (1995), Biochemistry 34, 5839-5858] were further characterized in terms of S-state cycling and photoactivation. Bare platinum electrode measurements of centrifugally deposited O2-evolving membranes isolated from the a-b loop mutants demonstrated a retarded appearance of O2 following single turnover flashes, although not to the extent of retardation seen in the Deltapsb0 mutant, which lacks the extrinsic manganese-stabilizing protein (MSP). Double flash measurements indicate that retarded O2 release in mutants coincides with a decrease in overall PSII turnover during the S3-[S4]-S0 transition. S2 and S3 decay measurements in the isolated membranes indicate that D1-D59N and D1-D61E have faster decays of these higher S-states in contrast to slowed decays in the Deltapsb0 mutant. Measurements of the flash interval dependence of photoactivation indicate that intermediates of photoactivation [light-dependent assembly of the (Mn)4 complex] are highly destabilized in the a-b loop mutants compared to both DeltapsbO and the wild-type: flash intervals of greater than 2 s result in the nearly complete decay of unstable photointermediate(s) in the D1-D59N and D1-D61E samples, whereas a similar loss does not occur until intervals even greater than 10 s in the DeltapsbO and wild-type samples. These results are consistent with a role for the residues D1-D59 and D1-D61 in modulating the redox properties of the higher S-states and, also, possibly in the binding the calcium ion involved in photoactivation.

Binding Sites↗
PubMed1999

CCK-8 can inhibit ingestive behavior by acting on the liver.

The possibility that cholecystokinin octapeptide (CCK-8) can inhibit ingestive behavior by acting on the liver was investigated. Male rats were trained to ingest an intraorally infused 1 M solution of sucrose and then injected with 10 microg CCK-8/kg. Intraperitoneal or hepatic portal vein, but not jugular vein, injection suppressed intake of the sucrose solution. Intraperitoneal injection was more potent than hepatic portal vein injection. Inhibition by hepatic portal vein injection was blocked by i.p. injection of 80 microg/kg of the CCK-A receptor antagonist L-364,718 or by hepatic vagotomy. The results support the hypothesis that CCK-8 can inhibit ingestive behavior via a hormonal action on the liver.

Animals↗