[Biomemetic surface modification of biomaterials related to tissue engineering].
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Animals↗
Biomedical subjects
F Shen
Publications and source records attributed to F Shen.
[Observation of therapeutic effect of Salviae miltiorrhiza and cytosine diphosphate-choline injection on patients with hypertensive cerebral hemorrhage].
OBJECTIVE: To assess the effect of Salviae miltiorrhiza (SM) injection in the treatment of hypertensive cerebral hemorrhage (HCH). METHODS: Fifty-one cases (age 50-78 years, 61.2 years on average) of HCH were randomly divided into three groups (SM + cytosine diphosphate-choline (CDP-C) group and para-aminomethyl benzoic acid (PAMBA) + CDP-C group as treated group, CDP-C group as control group) to observe the outcome of the clinical treatment, hematoma absorbability and changes of ADP-platelet agglutination rate (Pag), prothrombin time(PT) and function of the liver and kidney. RESULTS: The rate of good result (GR) and moderate disability (MD) in SM group was 85.71% with the method of Glasgow outcome score (GOS), others were 47.06% and 61.54% separately, they have significant difference, P < 0.05. Among them, SM group had best result. Compared the rate of hematoma absorbability of SM group with that of PAMBA, CDP-C groups, the difference was significant, P < 0.05. It did not affect the platelet coagulative function in SM group. CONCLUSION: SM injection could effectively improve the condition of patients with HCH, and without any side effect. It is worthwhile to be used in the clinical practice.
Aged↗
[Genetic epidemiological study on non-insulin dependent diabetes mellitus].
OBJECTIVE: To study the general genetic pattern of non-insulin dependent diabetes mellitus patients. METHODS: 1,608 children were investigated for NIDDM family history, and 280 nuclear families were collected. RESULTS: The prevalence rates of NIDDM among first-degree relatives (2.38%), the parents (26.00%), the siblings (2.44%) and the offsprings (1.24%) were higher than that in general population respectively. The s/q was 10.17 by Penrose method, which was close to 1/q(1/2). The p(0) was 0.0244 by simple segregation analysis, which was lower than 0.10. The heritability of NIDDM was 0.54, using the Falconer Threshold Model. CONCLUSION: NIDDM has a familial aggregation, but not fit to the mono-genetic models. NIDDM has the feature of multifactorial inheritance.
Adult↗
Differentiation of convalescent animals from those vaccinated against foot-and-mouth disease by a peptide ELISA.
We have identified continuous antigenic determinants within the amino acid sequences of the conserved nonstructural region containing proteins 2C and 3ABC of foot-and-mouth disease virus which can distinguish between the sera from vaccinated and infected animals. An ELISA based on a 3B peptide gave a positive reaction with sera from cattle, pigs, sheep and guinea pigs infected with all seven serotypes of the virus, but not with sera from vaccinated animals. In experiments with cattle and pigs to determine the duration of the antibody response, positive reactions were obtained as late as one year after infection. The advantages of using peptides from the nonstructural viral proteins instead of recombinant proteins for differentiating vaccinees from infected animals include their exquisite specificity, nonreactivity with antibodies against host cell-derived proteins (e.g. E. coli and insect cell proteins), and their ease of preparation.
Animals↗
Complete mapping of divergent amino acids responsible for differential ligand binding of folate receptors alpha and beta.
The folate receptor (FR) type alpha may be distinguished from FR-beta by its higher affinity for the circulating folate coenzyme, (6S)-5-methyltetrahydrofolate (5-CH3H4folate), and its opposite stereospecificity for reduced folate coenzymes. Previous studies showed that a single leucine to alanine substitution at position 49 of the mature protein sequence is responsible for the functional divergence of FR-beta (Shen, F., Zheng, X., Wang, H., and Ratnam, M. (1997) Biochemistry 36, 6157-6163); however, the results also indicated that the minimum requirement for conversion of FR-beta to the functional equivalent of FR-alpha should include amino acid substitution(s) downstream of residue 92 in addition to mutation of L49A. To pinpoint those residues, chimeric FR-betaL49A/FR-alpha constructs including progressively shorter segments of FR-alpha downstream of position 92 as well as selected point mutants were studied. Simultaneous substitution of Leu-49, Phe-104, and Gly-166 in FR-beta with the corresponding FR-alpha residues Ala, Val, and Glu, respectively, reconstituted the ligand binding characteristics of FR-alpha. The results also exclude a role for other residues in FR-alpha in determining its functional divergence. A homology model of FR-alpha based on the three-dimensional structure of the chicken riboflavin-binding protein is used to show the position of residues 49, 104, and 166 in relation to the hydrophobic cleft corresponding to the riboflavin-binding pocket.
Amino Acid Sequence↗
Synergistic down-regulation of signal transduction and cytotoxicity by tiazofurin and quercetin in human ovarian carcinoma cells.
Ovarian carcinoma is one of the most common causes of cancer death in women. Tiazofurin, a C-nucleoside, arrests the cell cycle at S phase and reduces the activities of PI (phosphatidylinositol) utilizing enzymes in signal transduction by depleting cellular GTP concentration. Quercetin (QN), a flavonoid, attacks the cell cycle at the G1 and S phase boundary and mainly inhibits PI kinase (1-phosphatidylinositol 4-kinase, EC 2.7.1.67) activity in the signal transduction pathway. Because tiazofurin and QN attack different biochemical targets and arrest different phases of the cell cycle, we tested the hypothesis that the two drugs might be synergistic against human carcinoma cells. In human ovarian carcinoma OVCAR-5 cells in growth inhibition assay, the IC50s (drug concentration that inhibits 50% of cell proliferation) for tiazofurin and QN were (mean +/- SE) 13 +/- 1.2 and 66 +/- 3.0 microM; in clonogenic assays they were 6 +/- 0.5 and 15 +/- 1.2 microM, respectively. When tiazofurin was added to cells followed 12 h later by QN, synergism was observed in both growth inhibition and clonogenic assays. The combination also yielded synergistic reduction of IP3 (inositol 1,4,5-trisphosphate) concentration in the cells which may explain, at least in part, the synergistic action of tiazofurin and QN in OVCAR-5 cells. The protocols yielding synergism may have implications in the clinical treatment of human ovarian carcinoma.
Antineoplastic Agents↗
Amplification of signal transduction capacity and down-regulation by drugs.
Recent work in this Laboratory showed increased activity of PI 4-kinase, PIP kinase and PLC in various cancer cells, indicating a stepped-up capacity for signal transduction. This elevated potential was paralleled with increased concentration of the end product of signal transduction, IP3. Current investigations showed that in normal cells the activities of the specific phosphatases (which degrade PIP2 and PIP and oppose those of the synthetic enzymes) were 4 to 5 orders of magnitude higher than those of the synthetic kinases. In hepatoma cells the specific phosphatase activities markedly decreased. Thus, in cancer cells the marked elevations in activities of the synthetic enzymes were opposed by a reduction in the activities of the degradative specific phosphatases. This enzymic imbalance is responsible, in part at least, for the elevated capacity of signal transduction and IP3 concentration. Since the enzymic activities measured were proportionate with time elapsed and amount of enzyme added, the alterations in activities should reflect changes in enzyme amounts. These alterations indicate a reprogramming of gene expression which should confer selective advantages to the cancer cells, marking out the elevated synthetic enzyme activities as potentially sensitive targets for drug treatment. We showed earlier that tiazofurin, which curtailed the biosynthesis of enzymes with short half-lives such as PI and PIP kinases, down-regulated signal transduction and brought down IP3 concentration. Quercetin and genistein chiefly inhibited PI-4 kinase and PIP kinase, respectively, and as a result reduced IP3 concentration in cancer cells. Current studies reveal that tiazofurin with quercetin, tiazofurin with genistein, and quercetin with genistein were synergistic in killing human cancer cells and in reducing signal transduction activity. In estrogen receptor-negative MDA-MB-435 human breast carcinoma cells which have elevated signal transduction activity, tamoxifen caused IC50S for growth inhibition and cytotoxicity of 12 and 0.7 microM, respectively. When tiazofurin was added to breast carcinoma cells, followed 12 hr later by tamoxifen, synergism was observed in growth inhibition, in clonogenic assays and in the reduction of IP3 concentration. The synergistic action of tiazofurin and tamoxifen and the other synergistic drug interactions outlined above may have implications in the clinical treatment of neoplasias.
Animals↗
Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours.
BACKGROUND: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. PATIENTS AND METHODS: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. RESULTS: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. CONCLUSIONS: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.
Adult↗
On the assessment of statistical significance in disease-gene discovery.
One of the major challenges facing genome-scan studies to discover disease genes is the assessment of the genomewide significance. The assessment becomes particularly challenging if the scan involves a large number of markers collected from a relatively small number of meioses. Typically, this assessment has two objectives: to assess genomewide significance under the null hypothesis of no linkage and to evaluate true-positive and false-positive prediction error rates under alternative hypotheses. The distinction between these goals allows one to formulate the problem in the well-established paradigm of statistical hypothesis testing. Within this paradigm, we evaluate the traditional criterion of LOD score 3.0 and a recent suggestion of LOD score 3.6, using the Monte Carlo simulation method. The Monte Carlo experiments show that the type I error varies with the chromosome length, with the number of markers, and also with sample sizes. For a typical setup with 50 informative meioses on 50 markers uniformly distributed on a chromosome of average length (i.e., 150 cM), the use of LOD score 3.0 entails an estimated chromosomewide type I error rate of.00574, leading to a genomewide significance level >.05. In contrast, the corresponding type I error for LOD score 3.6 is.00191, giving a genomewide significance level of slightly <.05. However, with a larger sample size and a shorter chromosome, a LOD score between 3.0 and 3.6 may be preferred, on the basis of proximity to the targeted type I error. In terms of reliability, these two LOD-score criteria appear not to have appreciable differences. These simulation experiments also identified factors that influence power and reliability, shedding light on the design of genome-scan studies.
Chromosome Mapping↗
Pharmacokinetics of buspirone following oral administration to rhesus monkeys.
Pharmacokinetics of buspirone and its active metabolite, 1-pyrimidinyl piperazine (1-PP) following oral administration were assessed in rhesus monkeys at doses used in chronic toxicology studies. The study was conducted over four periods in three male and three female rhesus monkeys. In the first three periods, buspirone hydrochloride solution was administered in a randomized manner by oral gavage at doses (expressed as buspirone free base) of 12.5, 25 and 50 mg kg(-1) once a day on days 1 and 7 and twice a day on days 2-6. In the last period, all monkeys received 25 mg kg(-1) buspirone as a single daily dose for 7 days. Serial plasma samples were collected for analysis of buspirone and 1-PP on days 1 and 7 in the first three periods and on day 7 in the last period for assessment of single dose and steady-state pharmacokinetics. Inter-animal variability in the pharmacokinetics of buspirone was high. Examination of Cmin vs time plots revealed that the steady state was attained by day 7 except for one monkey who demonstrated much higher Cmin values. For buspirone, dose proportionality was concluded for both Cmax and AUC on day 1 but not on day 7. The accumulation factor on day 7 for buspirone was nearly 5 for Cmax and 7 for AUC when compared with day 1. For 1-PP, dose proportionality was concluded except for Cmax in male monkeys on day 7. In contrast to buspirone, 1-PP showed less than 2-fold accumulation in Cmax and AUC values on day 7 compared with those on day 1. Exposure at a dose of 25 mg kg(-1) once daily was in between the 125 mg kg(-1) and 25 mg kg(-1) twice-a-day regimens. These results document dose-dependency in the steady-state pharmacokinetics of buspirone in rhesus monkeys.
Administration, Oral↗
[The mutation of deletion for glutathione S-transferase M1 gene in the tissue of hepatocellular carcinoma].
OBJECTIVE: To Study whether the mutation of deletion for glutathione S-transferase M1 (GSTM1) gene occurred during the development of hepatocellular carcinoma (HCC). METHODS: The genotypes of GSTM1 of 46 pairs of HCC tissue and the noncancerous liver tissue were detected by polymerase chain reaction (PCR). RESULTS: The frequency of GSTM1 null genotype for HCC tissue was 78.26%, but 65.22% for the noncancerous liver tissue (P<0.05). The GSTM1 null genotypes of 6 HCC tissue were transformed from the non- null genotypes of the noncancerous liver tissue. According to Hardy-Weinberg law., the rate of deletion mutation for GSTM1 gene was inferred to be 38.89%. CONCLUSION: The results suggested that the mutation of deletion for GSTM1 gene had occurred during the development of HCC.
Carcinoma, Hepatocellular↗
Ganglion cell losses underlying visual field defects from experimental glaucoma.
PURPOSE: To investigate the relationship between ganglion cell losses and visual field defects caused by glaucoma. METHODS: Behavioral perimetry and histology data were obtained from 10 rhesus monkeys with unilateral experimental glaucoma that was induced by argon laser treatments to their trabecular meshwork. After significant visual field defects had developed, the retinas were collected for histologic analysis. The ganglion cells were counted by light microscopy in cresyl violet-stained retina sections, and the percentage of ganglion cell loss (treated to control eye counts) was compared with the depth of visual field defect (treated to control eye thresholds) at corresponding retinal and perimetry test locations. Sensitivity losses as a function of ganglion cell losses were analyzed for Goldmann III, white and Goldmann V, and short- and long-wavelength perimetry test stimuli. RESULTS: The relationship between the proportional losses of ganglion cells and visual sensitivity, measured with either white or colored stimuli, was nonlinear. With white stimuli, the visual sensitivity losses were relatively constant (approximately 6 dB) for ganglion cell losses of less than 30% to 50%, and then with greater amounts of cell loss the visual defects were more systematically related to ganglion cell loss (approximately 0.42 dB/percent cell loss). The forms of the neural-sensitivity relationships for visual defects measured with short- or long-wavelength perimetry stimuli were similar when the visual thresholds were normalized to compensate for differences in expected normal thresholds for white and colored perimetry stimuli. CONCLUSIONS: Current perimetry regimens with either white or monochromatic stimuli do not provide a useful estimate of ganglion cell loss until a substantial proportion have died. The variance in ganglion cell loss is large for mild defects that would be diagnostic of early glaucoma and for visual field locations near the fovea where sensitivity losses occur relatively late in the disease process. The neural-sensitivity relationships were essentially identical for both white and monochromatic test stimuli, and it therefore seems unlikely that the higher sensitivity for detecting glaucoma with monochromatic stimuli is based on the size-dependent susceptibility of ganglion cells to injury from glaucoma.
Animals↗
Ribavirin and quercetin synergistically downregulate signal transduction and are cytotoxic in human ovarian carcinoma cells.
Ribavirin, a nucleoside, well known as a broad-spectrum antiviral agent, is extensively used in the treatment of hepatitis C infections. Ribavirin inhibits IMP DH (EC 1.1.1.205) activity and reduces cellular GTP concentration. Quercetin, a plant flavonoid, exhibits antineoplastic activity and inhibits PI 4-kinase (EC 2.7.1.67) and PIP 5-kinase (EC 2.7.1.68) activity. Ribavirin and quercetin attack the cell cycle at the G1 and G1/S boundary, respectively. Because they act on different enzyme targets and arrest the cell cycle at different phases, we tested the hypothesis that ribavirin and quercetin might be synergistic in growth inhibition and cytotoxicity. Human myeloma 8226 and human ovarian carcinoma OVCAR-5 cells were studied because in these cells IMP DH activity increased 14- and 20-fold, respectively, and PI 4- and PIP 5-kinase activities were also elevated. In growth inhibition for ribavirin and quercetin in myeloma 8,226 cells IC50s were 40 and 70 microM, respectively. In OVCAR-5 cells in growth inhibition and clonogenic assays for ribavirin IC50 and LC50 of 35 and 23 microM, respectively, were observed. When quercetin was added 24 h after ribavirin, synergistic antiproliferative action was observed in both myeloma 8,226 and OVCAR-5 cells. Synergistic action was also obtained in OVCAR-5 cells in clonogenic assay when ribavirin was combined with quercetin in the sequence described above. The mechanism of action is provided, in part at least, by the synergistic reduction of signal transduction (IP3 concentration) by ribavirin and quercetin. Ribavirin and quercetin in combination might be of interest in the treatment of myeloma and ovarian carcinoma.
Antineoplastic Agents↗
[Effect of different immunomodulators on macrophage function in rats with scald injury].
OBJECTIVE: To explore effect of different immunomodulators on macrophage (M phi) functions in rats with scald injury. METHODS: The M phi functions in various groups of rats with scald on the 5th and 10th day after scald were respectively determined with methods of McAb APAAP, agar bacteriolytic plate and MTT colorimetry. RESULTS: The results showed that: 1. after scald, presenting rate of Ia antigen, ability of antigen presentation, phagocytic power to candida albicans and lysozyme ability of M phi were significantly decreased, the capacity of M phi secreting TNF was markedly increased compared with those of the normal group, and the differences were significant (P < 0.01); 2. after the therapy with immunodulators, the above functions of M phi in rats with scald improved markedly. As compared with those of the control group, differences were significant (P < 0.01). CONCLUSION: The specific immune RNA, which is administered by intraperitoneal injection early after scald, can markedly improve immune functions of rats with scald.
Adjuvants, Immunologic↗
[Significance of TNM clasification in prognostic evaluation of hepatocelluar carcinoma following surgical resection].
OBJECTIVE: To investigate correlation between TNM classification of HCC and local-regional cancer-free survival time after hepatectomy. METHODS: A retrospective survey was carried out in 1,725 cases with hepatocellular carcinoma (HCC) receiving radical or relatively radical operation from Jan. 1, 1990 through Dec. 31, 1995. The follow-up rate was 84.46%. The factors under consideration were analysed using Cox proportional hazards survival model and Kaplan-Meier estimation. RESULTS: Univariate analysis showed that 13 clinical and pathologic factors, including clinical stage, age, portalvein tumor thrombus, tumor number found before and/or during operation, radical or relatively radical resection, size of tumor, growing pattern, encapsulation of tumor, daughter nodules (including microscopic nodules), vascular invasion, TNM stage, AFP level after hepatectomy and so on, might all influence local-regional cancer-free survival time. Multivariate analysis revealed four significant prognostic factors: tumor number found before operation, tumor size, daughter nodules and vascular invasion. These four factors were encompassed in TNM staging. By Kaplan-Meier estimation, tumor-free survival rate at 0.5, 1, 3, and 5 years was as follows: at stage I 90.7%, 79.1%, 45.8%, 24.6%; at stage II 86.6%, 75.5%, 51.8%, 38.4%; at stage III 62.6%, 41.5%, 20.6%, 15.9; at stage IV a 33.0%, 18.6%, 8.0%, 5.3%; at stage IVb 42.3%, 35.3%. The mean tumor-free survival time of stage I to IVb was 34.36, 38.25, 10.01, 4.06 and 4.26 months, respectively. There was no significant difference in tumor-free survival rate btween stage I and II. CONCLUSION: TNM stage is one of the most significant prognostic factors determining tumor-free survival after HCC resection.
Adolescent↗
[Management of retrohepatic inferior vena cava injuries in hepatectomy for neoplasm].
OBJECTIVE: To evaluate the management of injured retrohepatic inferior vena cava during hepatectomy for neoplasm. METHODS: Step-by-step hepatic vascular exclusion, finger pressing, finger pinching, and surface-to-surface sewing up were used in the management of injured retrohepatic inferior vena cava in 16 cases of hepatic resection. RESULTS: In all cases, bleeding was stopped immediately after the procedure without any death and rebleeding. All cases survived after 6 - 18 month follow-up. CONCLUSIONS: The methods mentioned above are simple, useful, time-saving, safe and effective.
Adult↗
[Loss of heterozygosity and microsatellite instability in the region including BRCA1 of breast cancer in Chinese].
OBJECTIVE: To shed light on the relationship between BRCA1 gene and breast cancer in Chinese Han women. METHODS: Four microsatellites DNA (D17S855, D17S579, D17S1327 and THRA1) within the BRCA1 gene were used as polymorphic markers. A study of loss of heterozygosity(LOH) and microsatellite instability(MSI) at the above- mentioned 4 microsatellites of 50 breast cancer patients was conducted by using PCR -PAUGE-DNA silver staining (polymerase chain reaction-polyacrylamide urea gel electrophoresis) method. RESULTS: Twenty-nine or 58% of the informative cases showed LOH; 35.71%, 15. 38%, 18.18%, and 26.19% of the informative cases showed positive LOH at the D17S855, D17S579, D17S1327 and THRA1 loci respectively. The rate of MSI was 46%, and the rates of MSI at the four loci were 16%, 18%, 18% and 12% respectively. Further study on the associations between the phenomena of LOH and MSI and different clinical stages revealed that MSI was an early event in mammary tumorigenesis while LOH occurred at a later stage. CONCLUSION: All of these suggest that breast cancer in Chinese be somehow linked to BRCA1.
Breast Neoplasms↗
Experimental autoimmune encephalomyelitis is exacerbated in mice lacking the NOS2 gene.
Nitric oxide is believed to be a prominent mediator of inflammation based in part on the correlative expression of the inducible nitric oxide synthase (iNOS) gene in various pathologies. The resulting high output of the highly reactive molecule nitric oxide is then believed to play an important role in the evolving inflammatory response. Studies have shown that iNOS and nitric oxide are present in the tissues of patients with multiple sclerosis (MS). In rodent models of MS, experimental autoimmune encephalomyelitis (EAE), it has been shown that nonspecific NOS inhibitors partially ameliorate the disease. To determine the importance of iNOS in this model of MS, we induced EAE in mice containing a disrupted iNOS (NOS2) gene. Surprisingly, by day 24, the NOS2 knockout mice had a greater incidence of EAE than wild-type control mice (75 vs 12%), and had a higher average severity score (2.42 vs 0.44). These differences appear to result largely from the failure of the disease to remit in NOS2 KO mice. Wild-type mice have a profound ability to reverse EAE (82%) compared with the knockout mice (19%). This result implies that iNOS may in some instances play a protective role in autoimmune-mediated tissue destruction.
Amino Acid Sequence↗