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Biomedical subjects

C L Li

Publications and source records attributed to C L Li.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of metformin on patients with impaired glucose tolerance.

AIMS: To evaluate the effect of metformin on glucose metabolism, insulin sensitivity and rate of conversion diabetes in people with impaired glucose tolerance (IGT). METHODS: Seventy subjects with IGT were randomized under double-blind conditions to receive either placebo (n = 37) or metformin (n = 33) at a dosage of 250 mg three times daily for a duration of 12 months. Glycaemic control, plasma insulin and other biochemical indexes were assessed before and after 3, 6 and 12 months. RESULT: At 12 months the conversion rate to diabetes was 16.2% in the placebo group compared to 3.0% for the metformin group (P = 0.011). Of subjects treated with metformin for 12 months, 84.9% became normoglycaemic compared to 51.4% of those receiving the placebo. Significant improvements in fasting glucose, glucose tolerance and insulin sensitivity were found at 12 months and at intermediate clinic assessments. CONCLUSIONS: Metformin can improve glucose metabolism in IGT patients and may be a treatment option in their management of IGT subjects.

Adult↗
PubMed1999

Effect of aging on gender differences in neural control of heart rate.

To clarify the influence of gender on sympathetic and parasympathetic control of heart rate in middle-aged subjects and on the subsequent aging process, heart rate variability (HRV) was studied in normal populations of women (n = 598) and men (n = 472) ranging in age from 40 to 79 yr. These groups were divided into eight age strata at 5-yr intervals and were clinically diagnosed as having no hypertension, hypotension, diabetic neuropathy, or cardiac arrhythmia. Frequency-domain analysis of short-term, stationary R-R intervals was performed, which reveals very-low-frequency power (VLF; 0.003-0.04 Hz), low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF; 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF and HF power in normalized units (LF% and HF%, respectively). The distribution of variance, VLF, LF, HF, and LF/HF exhibited acute skewness, which was adjusted by natural logarithmic transformation. Women had higher HF in the age strata from 40 to 49 yr, whereas men had higher LF% and LF/HF between 40 and 59 yr. No disparity in HRV measurements was found between the sexes in age strata >/=60 yr. Although absolute measurements of HRV (variance, VLF, LF, and HF) decreased linearly with age, no significant change in relative measurements (LF/HF, LF%, and HF%), especially in men, was detected until age 60 yr. We conclude that middle-aged women and men have a more dominant parasympathetic and sympathetic regulation of heart rate, respectively. The gender-related difference in parasympathetic regulation diminishes after age 50 yr, whereas a significant time delay for the disappearance of sympathetic dominance occurs in men.

Adult↗
PubMed1999

The impact of department sub-division on hospital performance.

BACKGROUND: Chang Gung Memorial Hospital is the first hospital in Taiwan to adopt the 'sub-division management'. The hospital sub-divided extensively growing departments into two or more similar sub-divisions. This study compared the relative performance before and after the implementation of "sub-division management". METHODS: The cardiac department of Chang Gung Memorial Hospital was subdivided into Cardiac I and Cardiac II in July 1992. This study collected the managerial information of cardiac inpatients from 1991 through 1993 in Chang Gung Memorial Hospital. By exploring the effects of the "sub-division management" and other confounding factors, we tried to find out the possible impact they brought to hospital performance. RESULTS: Considering a time trend effect, the results of regression indicate that 'sub-division' mechanism had little effect on departmental performance. However, the performance is different between Cardiac I and Cardiac II in the aspect of total expenditure per admission, average length of stay, and average number of discharge per physician. These differences might be affected by the characteristics of physicians' sub-specialties rather than the implementation of sub-division management. CONCLUSION: The significant decrease in mortality rate of patients in the cardiology department after the implementation might suggest that the quality of care in the cardiology department increased after the introduction of sub-divisions. The long-term effects of practice behavior induced by competition within and between sub-divisions require further organizational and behavioral studies.

Efficiency↗
PubMed1999

[Study on gene-dosage effect of high level expression of the yeast glucoamylase genes].

Diploid strains homozygous for both MAT allele and STA genes (a/a, STA1/STA1 or STA2/STA2 or STA3/STA3) and diploid strains homozygous for MAT allele but intercombinative for STA genes (a/a, STA1/STA2 or STA2/STA3 or STA1/STA3) were constructed by means of the protoplast fusion or the colchicine treatment. According to glucoamylase activity in YPS medium, we studied the gene-dosage effect and their interrelation of these three polymeric genes coding for glucoamylase. The results of the glucoamylase activity determination showed that the gene-dosage effect of glucoamylase is obvious in diploid and triploid strains homozygous for both MAT allele and STA gene, such as the glucoamylase activity of a diploid strain SFY56-6 and a triploid strain SFY56-104 homozygous for both MAT allele and STA genes were respectively 2.35 and 3.18-fold as compared with that of the their parental strain IATA-Y56 that is a haploid Saccharomyces diastaticus. Moreover, the glucoamylase activity of diploid strains homozygous for MAT allele but intercombinative for STA genes also showed the combinative gene-dosage effect to a certain extent.

Gene Dosage↗
PubMed1999

[In vivo degradation of PDLLA membrane made in China:a study on rats]

OBJECTIVE:The possibility of absorbable membrane materials poly PDLLA using in guided tissue regeneration(GTR)was evaluated through degradation in vivo. METHODS: membranes were implanted in the drosal subcutis of rats for periods of 1,2,4,8,12weeks.The surface morphology was observed,the mass loss was measured and molecular weight was determined with gel permeation chromatography(GPC). RESULTS: The mass loss were similar to those in virto,and molecular weight changes were the same to those in vitro,but the number average molecular weight did not fit the Pitt's model. CONCLUSION: The surface morphology of PDLLA membrane remained relatively unaltered,its integrity kept more than 12 weeks,which could meet the requirements of GTR.

Journal Article↗
PubMed1998

PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate.

Deletion of the q23-24 region of human chromosome 10 is one of the most frequent genetic alterations in prostate cancer, suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. A candidate gene, PTEN/MMAC1, has been identified from this chromosomal region; mutations of this gene have been found in various advanced tumors and cell lines including those of prostate cancer. To further define the role of PTEN/MMAC1 in the development of prostate cancer and its spectrum of genetic alterations, we analysed 40 pT2 or pT3 prostate tumors for allelic loss, mutations, and homozygous deletions using PCR-based methods. Six tumors showed loss of heterozygosity for one of the ten markers analysed, while one tumor showed loss of two markers. None of the markers within PTEN/MMAC1 was lost. Direct sequencing of PCR amplified exons and intron/exon junctions of all 40 tumors revealed three sequence variants, one of which was a point mutation in exon 9, while the other two were polymorphisms. Using multiplex PCR, no homozygous deletions were detected in any of the neoplasms. Our results showing a low frequency of alterations of PTEN/MMAC1 in pT2 and pT3 prostate cancers suggest that this gene plays an insignificant role in the development of most low stage carcinomas of the prostate.

Adult↗
PubMed1998

Expression of the Wilms' tumor suppressor gene, WT1, is upregulated by leukemia inhibitory factor and induces monocytic differentiation in M1 leukemic cells.

The Wilms' tumor gene, WT1, encodes a transcription factor of the Cys2-His2 zinc finger type. The functional significance of WT1 expression in leukemias, in addition to tissues and cell lines of hematopoietic origin, has not been determined. Using the murine myeloblastic leukemia cell line M1 as a model for macrophage differentiation, expression of WT1 is shown to be activated in M1 cells 24 hours after differentiation induction by leukemia inhibitory factor (LIF). Upregulation of WT1 in these cells is associated with cellular differentiation, coinciding with expression of the monocyte/macrophage marker c-fms, and the appearance of mature cells. WT1 isoforms lacking the KTS insert are unable to be ectopically expressed in M1 cells. Stable expression of the WT1 isoforms containing the KTS insert leads to spontaneous differentiation of the M1 myeloblasts through the monocytic differentiation pathway. These cells express c-fms, in addition to the myeloid-specific cell surface marker Mac-1. Exposure of these cells to LIF results in the rapid onset of terminal macrophage differentiation, accompanied by apoptotic cell death. These results show that the WT1 gene is an important regulator of M1 cell monocytic differentiation in vitro, and suggests a potential role for this gene in the molecular control of hematopoiesis.

Animals↗
PubMed1998

Progression to type 2 diabetes among high-risk groups in Kin-Chen, Kinmen. Exploring the natural history of type 2 diabetes.

OBJECTIVE: To examine the natural history of 654 high-risk subjects (340 men and 314 women) with fasting hyperglycemia (first fasting plasma glucose [FPG] level 5.6-7.8 mmol/l) who also exhibited 2-h postload glucose concentrations < 11.1 mmol/l and an FPG level < 7.8 mmol/l in a 75-g oral glucose tolerance test (OGTT). We were particularly interested in comparing the likelihood of developing type 2 diabetes for those with persistent fasting hyperglycemia (PFH), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). PFH is a relatively new definition, and those with PFH used to be defined as NGT according to WHO criteria. RESEARCH DESIGN AND METHODS: Subjects were located in a 1992-1994 community-based population survey and followed up and reexamined during 1995-1996. An OGTT was used to determine who had progressed to type 2 diabetes. Risk factors predictive of subsequent progression to type 2 diabetes were determined by comparing baseline variables from the 1992-1994 survey with data of those who had or had not progressed to type 2 diabetes in 1995-1996. RESULTS: Of 654 high-risk subjects screened in the baseline survey, 481 (73.5%, 255 men and 226 women) were followed up. Of these, 8.1% had progressed to diabetes (4.1% progression/year, 95% CI 2.3-5.9). Of 131 baseline IGT subjects, 17.6% progressed to diabetes (8.8% progression/year, 6.3-11.3), but only 7.4% of 95 PFH subjects (3.7% progression/year, 2.0-5.4) and 3.5% of 255 NGT subjects (1.8% progression/year, 0.1-3.0) progressed to diabetes. CONCLUSIONS: The rates of progression to type 2 diabetes were lowest from the NGT subgroup, highest from the IGT group, with the PFH group in the middle, suggesting that PFH might be a transitional condition that precedes IGT and diabetes. Other significant predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia, baseline FPG, and 2-h plasma glucose concentration.

Adult↗
PubMed1998

Human mu-opioid receptor overexpressed in baculovirus system and its pharmacological characterizations.

AIM: To overexpress human mu-opioid receptor (muOR) with characteristics similar to those of mammalian origin. METHODS: Human muOR with a tag of 6 consecutive histidines at its carboxyl terminus was expressed in recombinant baculovirus infected Sf9 insect cells. Then the pharmacological characterizations of the product were studied by receptor binding assay and cAMP assay. RESULTS: The maximal binding capacity for the [3H]diprenorphine and [3H]ohmefentanyl (Ohm) were 9.1 +/- 0.7 and 6.52 +/- 0.23 nmol/g protein, respectively. The [3H]diprenorphine or [3H] Ohm binding to the receptor expressed in Sf9 cells was strongly inhibited by alpha-selective agonists [D-Ala2, N-methyl-Phe4, glyol5] enkephalin (DAGO), Ohm, and morphine, but neither by the delta-selective agonist [D-Pen2, D-Pen5] enkephalin (DPDPE) nor by the kappa-selective agonist ¿trans-(+/-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]¿ benzacetamide (U50488). NaCl 100 mmol.L-1 and guanosine triphosphate (GTP) 50 mumol.L-1 could reduce mu agonists Ohm and etorphine affinity binding to the expressed muOR. DAGO and Ohm effectively inhibited forskolin-stimulated cAMP accumulation. This agonist-dependent effect was blocked by opioid antagonist naloxone. CONCLUSION: The overexpression of human muOR with a tag of six consecutive histidines at its carboxyl terminus in Sf9 insect cells retained the characteristics of wild-type human muOR.

Animals↗
PubMed1998

[Biosynthesis of a single peptide chain containing human chorionic gonadotropin beta and ovine common alpha subunits tandem].

hCG beta-oLH alpha chimeric cDNA was constructed by using overlapping PCR to contact the codons of C-terminal end of hCG beta with the codons of N-terminal end of oLH alpha, then it was subcloned into nuclear polyhedrosis virus (AcNPV) expression vector pVL1393 to construct expression vector pVL1393-hCG beta-oLH alpha. The insect cells (Sf9) were cotransfected by the expression vector pVL1393-hCG beta-oLH alpha and BaculoGold AcNPV linearized genomic DNA, and recombinant viruses AcNPV-hCG beta-oLH alpha were screened out by plaque assay. Further the insect cells were infected by the recombinant viruses, the recombinant hCG beta-oLH alpha was purified by immunoaffinity chromatography column coupling anti-hCG beta monoclonal antibody from the conditioned media of infected cells. The results of SDS-PAGE silver staining and western blotting showed that hCG beta-oLH alpha single peptide chain had apparent molecular weights of 40.5 kD and 38.0 kD under non-reducing and reducing conditions respectively, indicating the occurrence of disulfide bonds and significant tertiary structure in the single peptide chain. From the results of competitive inhibition of 125I-hCG beta binding we can conclude that the anti-hCG beta antibody-binding activity of hCG beta-oLH alpha chimera is lower than that of native hCG, but higher than that of native hCG beta. Therefore, we assume that the hCG beta-oLH alpha chimera should have potential application as a target antigen of anti-hCG fertility regulatory vaccine.

Animals↗
PubMed1998

[Expression of murine interleukin 12(mIL-12) in insect cells].

Since human IL-12 is species-specific in its functions and elicits little biological responses from mouse lymphocytes, it is necessary to express recombinant murine IL-12 for the usage in studying the effects of this cytokine in various rodent models. Thereby, we can investigate the role of IL-12 in immune response in vivo and evaluate its potential clinical utility. Thus, we firstly constructed two expression vectors, pVL1393-mp40 and pVL1393-mp35. They were used to co-transfect the insect cells(Sf9) separately with linearized polyhedrosis virus genomic DNA. Two kinds of recombinant viruses AcNPV-mp40 and AcNPV-mp35 were visually screened out, and mp40 and mp35 were co-expressed in the insect cells co-infected by AcNPV-mp40 and AcNPV-mp35. The results of real-time Biomolecular Interaction Analysis (BIA) and Northern blot demonstrated that the recombinant mIL-12 was expressed successfully in the insect cells. The molecular weights of recombinant mp40 and mp35 were 40 KDa and 22 KDa on SDS-PAGE under reducing conditions, respectively. The apparent molecular weight of recombinant mIL-12 is 80 KDa under non-reducing conditions of Western blot. Biological activity of the recombinant product was detected in conditional medium using antibody-capture bioassay. The expression level of recombinant mIL-12 was about 10-15 micrograms/10(6) cells, as compared with the calibration curve of mIL-12.

Animals↗
PubMed1998

Intrasynaptosomal free calcium and nitric oxide metabolism in central nervous system oxygen toxicity.

BACKGROUND: Central nervous system (CNS) oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for nitric oxide (NO) has been proposed, although recent data have indicated that NO is synthesized from L-arginine by an enzyme, NO synthase (NOS). The enzyme is dependent on free calcium (Ca2+) concentration, therefore increases in intracellular Ca2+ may constitute the physiological and pathophysiological mechanisms for stimulating the synthesis of NO. METHODS: In this study, the intrasynaptosomal free calcium concentration ([Ca2+]i) was measured by the fluorescence of fura-2/AM, and cGMP (as an indirect marker of NO levels) was by radioimmunoassay (RIA) in the rat hippocampus after hyperbaric oxygen (HBO) exposure. We also investigated the effects of daurisoline (DSL, calcium channel blocker) and N-nitro-L-arginine (LNNA, NOS inhibitor) on the above biochemical parameters and the development of oxygen toxicity. RESULTS: The results show that when the rats were exposed to HBO at 0.5 MPa the intrasynaptosomal Ca2+ and cGMP levels increased by two and three times, respectively, whereas with the use of DSL prior to HBO, the accumulation of [Ca2+]i and cGMP dropped to 56% and 60%, correspondingly. In the rats medicated with LNNA prior to HBO. [Ca2+]i and cGMP levels dropped to 70% and 36% of the HBO group. At the same time, the appearance of CNS oxygen toxicity was delayed and the survival rate increased. The protective effects of LNNA were reversed by L-arginine pretreatment. These findings suggest that the neuronal Ca2+ overload during HBO exposure is a major factor in the pathogenesis of CNS O2 toxicity, and cGMP-NO pathways may be directly involved in HBO-induced seizures.

Animals↗
PubMed1998

[ACTH receptor, ACTH receptor anomaly, and familial glucocorticoid deficiency].

Familial glucocorticoid deficiency (FGD) is an autosomal recessive syndrome with hereditary adrenocortical unresponsiveness to ACTH. After the cloning of ACTH receptor or melanocortin-2 receptor (MC-2R) cDNA, several kinds of mutations in the receptor genes have been reported. However, the apparently normal ACTH receptor gene in some affected children suggests that the etiology of FGD is heterogeneous. In this short review, we describe the recent advances in the molecular biology of ACTH receptor genes, its post-receptor signal transduction in the adrenocortical cells, and the molecular genetics of the FGD and a related syndrome, Allgrove syndrome. We also discuss that this kind of work will help us to understand better about the molecular mechanism of the glucocorticoidogenesis in the human being.

Glucocorticoids↗
PubMed1997

Predominant expression of murine Bmx tyrosine kinase in the granulo-monocytic lineage.

In the course of systematic cloning of protein tyrosine kinases (PTKs) expressed in hematopoietic stem and progenitor cells, we have identified the murine homologue of human Bmx. It encodes a protein containing the five domains characteristic of the Tec family of cytoplasmic src-related PTKs: pleckstrin homology (PH), Tec homology (TH), src homology 3 and 2 (SH3 and SH2), and tyrosine kinase (TK). In adults, Bmx expression was found primarily in bone marrow and at a lower level in lung and heart. During fetal development it was also found in the spleen at late stage of gestation and in neonates. Analysis of bone marrow subpopulations showed that Bmx was expressed in the progenitor cell population and maturing hematopoietic cells of the granulo/monocytic lineage where expression increased with maturation and differentiation. At the periphery, a high level of Bmx expression was also found in neutrophils and monocytes/macrophages. Bmx expression was not detected in the primitive hematopoietic stem cell population, and cells of the B-, T-, and erythroid-lineages. It was also not detected in most of the cell lines examined. Our results indicate that Bmx is another member of the Btk/Itk/Tec PTK family, which is predominantly expressed in the granulo-monocytic lineage within the hematopoietic system.

Adult↗
PubMed1997

Antisense transcription of a murine FGFR-3 psuedogene during fetal developement.

In a search for new protein tyrosine kinases (PTKs) in early hemopoietic cells, we have identified a sequence closely related to the Fibroblast Growth Factor Receptor (FGFR) family. A cDNA isolated from a mouse embryo library was 89% identical to FGFR-3 in both its coding and 3' untranslated regions. However, the region homologous to exons 5 to 9 of FGFR-3 was missing. In addition, the ORF was interrupted by several stop codons and frame shifts, indicating that this sequence is not functional. These transcripts were therefore copied from a novel FGFR-3 pseudogene, that we called psiFGFR-3. Partial analysis of this gene showed the absence of introns, which is a characteristic feature of a processed pseudogene. psiFGFR-3 gene was localized on Chromosome 1H4-6. Its transcription was shown to be antisense and its expression was restricted to fetal tissues. These results indicate that psiFGFR-3 has been inserted in Chromosome 1 in antisense orientation close to a heterologous promoter.

Alternative Splicing↗
PubMed1997

Cytokine receptor expression on hematopoietic stem and progenitor cells.

Hematopoietic stem and progenitor cell populations were obtained by fluorescence activated cell sorting of murine bone marrow (BM) cells into Rhodamine-123io lineage-Ly6A/ E+ c-kit+ (primitive stem cells highly enriched for long-term BM repopulating activity), Rhodamine-123med/hl lineage- Ly6A/E+ c-kit+ (mature stem cells highly enriched for shortterm BM repopulating activity and day 13 spleen colony-forming activity) and lineage- Ly6A/E- c-kit+ (enriched for in vitro colony forming cells) populations. Neither stem cell population responds to single cytokines in vitro and each requires the synergistic action of two or more cytokines for proliferation, whereas the progenitor cell population proliferates in response to single cytokines. Since each of these cell populations was sorted as c-kit+, they express receptors for stem cell factor. Cell populations were also analyzed by autoradiography for their ability to specifically bind iodinated cytokines and this revealed that both stem cell populations expressed receptors for interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, and granulocyte colony-stimulating factor (G-CSF), but lacked receptors for macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Cells within the progenitor cell population specifically bound IL-3, GM-CSF, G-CSF, IL-6, and IL-1 alpha, whereas no receptors were detected for M-CSF and LIF. Within each cell population examined, heterogeneity was observed in the percentage of cells labeled and the number of receptors per cell. These results suggest that stem cell populations can be further subdivided according to their cytokine receptor profile and it will be of interest to determine if such subpopulations have distinctive functional properties.

Animals↗
PubMed1997

A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy.

The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient, with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophila. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases: however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.

Autopsy↗