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Biomedical subjects

J Fang

Publications and source records attributed to J Fang.

At least 235 records · Page 13Linked to original sources

Involvement of CYP3A4 and CYP2D6 in the metabolism of haloperidol.

1. Human cytochrome P450 (CYP) isoenzymes expressed in a human cell line were used to elucidate their involvement in the metabolism of haloperidol (HAL). 2. It was found that CYP3A4 catalyzes the metabolism of HAL to HAL 1,2,3,6-tetrahydropyridine (HTP). HTP is further metabolized to HAL pyridinium (HP+) by both CYP3A4 and CYP2D6. 3. CYP3A4 and CYP2D6 are also responsible for the N-dealkylation of HAL. The N-dealkylation of reduced HAL (RH) was observed, which is catalyzed by CYP3A4. In addition, CYP3A4 also catalyzes the oxidation of RH back to HAL. 4. These results are discussed in terms of the metabolic interactions of HAL with other drugs and how this knowledge may be used to reduce the movement disorders induced by HAL.

Biotransformation↗

Inhibition of brain interleukin-1 attenuates sleep rebound after sleep deprivation in rabbits.

It is hypothesized that interleukin-1 (IL-1) is involved in physiological sleep. If this hypothesis is correct, inhibition of IL-1 should attenuate sleep responses after sleep deprivation. We tested the effect of intracerebroventricular or intravenous injection of an IL-1 inhibitor, an IL-1 receptor fragment (IL-1RF), on sleep rebound after sleep deprivation in rabbits. Six hours of total sleep deprivation significantly increased non-rapid eye movement sleep (NREMS) and enhanced electroencephalogram slow-wave activity during NREMS. Intracerebroventricular treatment with the IL-1RF (50 micrograms) significantly attenuated the sleep responses after sleep deprivation. Furthermore, 1.0 mg/kg i.v. injection of the IL-1RF significantly suppressed spontaneous NREMS in rabbits that were not sleep deprived. However, intravenous administration of the IL-1RF (1.0 mg/kg) failed to attenuate the sleep responses following the 6-h sleep deprivation period. These results support the hypothesis that central pools of IL-1 are important for physiological sleep regulation.

Animals↗

Spatial polarization of insulin-like growth factor receptors on the human syncytiotrophoblast.

The expression of IGF receptors on the maternal-facing, microvillous membrane (MVM) surface and the fetal-facing, basal membrane (BM) surface of the syncytiotrophoblast was studied using standard ligand binding assays, covalent cross-linking techniques, and immunoblot analysis. Scatchard analysis of [125I]IGF-I and -II binding revealed the presence of both high and low affinity binding sites associated with each membrane preparation that did not clearly distinguish between the two membrane preparations. Cross-linking analysis, however, demonstrated type I and type II IGF receptors associated primarily with MVM, suggesting that nonreceptor binding sites may contribute to total membrane binding. Ligand blot analysis revealed that BM are uniquely associated with 29- and 24-kD IGF binding proteins (IGFBPs). [125I]QAYL-IGF-I, having reduced affinity for IGFBPs, was therefore used to study receptor-specific binding. Approximately 5-fold more type I IGF receptors were shown to be associated with MVM than BM by Scatchard and cross-linking analyses. This was confirmed by immunoblot analysis. By contrast, immunoblot analysis revealed approximately 50-100% more type II IGF receptor protein associated with BM, whereas cross-linking to [125I]IGF-II revealed a MVM predominance. In the presence of 5 mM mannose 6-phosphate, however, a substantial increase in [125I]IGF-II cross-linked to the type II IGF receptor was observed in BM but not MVM consistent with immunoblot analysis. These data demonstrate that type 1 and unoccupied type II IGF receptors are expressed primarily on the maternal-facing. MVM surface of the syncytiotrophoblast.

Embryonic and Fetal Development↗

[Management of the forensic DNA typing laboratory].

This article evaluates the concept of DNA technology in the practice of forensic sciences and discusses the problems about the experimental conditions of the DNA laboratory, the qualification of technical personnel, the standardization of the creteria, relations between DNA typing and routine serology tests and so on.

DNA Fingerprinting↗

[Correlation between hypomethylation of c-myc and c-N-ras oncogenes and pathological changes in human hepatocellular carcinoma].

OBJECTIVE: To evaluate the molecular biological mechanism of human hepatocellular carcinoma--DNA methylation pattern of certain oncogenes. METHODS: Methylation patterns of c-myc, c-N-ras oncogenes in human hepatocellular carcinoma were studied by the Southern blot technique and HpaII/MspI restriction endonucleases. The pathological changes were also analyzed. RESULTS: The c-myc and c-N-ras oncogene fragments were hypomethylated in DNA samples derived from cancerous (30.3% and 60.1%) and adjacent paracancerous (12.1% and 30.3%) liver tissues. Hypomethylation of c-myc gene in multifocal type was significant as compared with unifocal type (P < 0.05). It is also found that c-N-ras gene hypomethylation had a strong correlation with tumor size (P < 0.01). CONCLUSION: The decrease of DNA methylation is present at the stage of liver carcinoma, and hypomethylation of c-myc, c-N-ras genes is correlated with the tendency of infiltration and metastasis.

Adult↗

[Studies on polysaccharide peptide with high performance gel permeation chromatography].

High performance gel permeation chromatography (HPGPC) has been widely used in the fraction and molecular-weight (MW) estimation of polysaccharides. In this paper, we estimated the MW of major component of polysaccharide-peptide from Corilous versicolor (PSP). These three-components were separated by using two column system (TSK-40 and TSK-50 gel columns) and different NaCl concentration in mobile phase. Calibration curve was prepared from the known MW Dextran T-system. It was found that the MW of PSP was changed in accordance with ion concentration of mobile phase. The MWs of the main component are more than 500000, 120000-19000 and less than 10000 respectively as the NaCl concentrations in mobile phase were less than 0.002, 0.006-0.04 and more than 0.06mol/L. The results showed that the MW of polysaccharide-peptide determined by HPGPC is a relative value that is changed with the concentration of mobile phase. The reason is that the molecular configuration and size of polysaccharide-peptide are changed along with electrolyte concentration in mobile phase. That is, the lower the electrolyte concentration is, the larger the molecular size of polysaccharide-peptide is. We suggest that it is still useful for quality control of PSP as the mobile phase is fixed.

Chromatography, Gel↗

[Simultaneous determination of 16 elements in decoction solution of Chinese herbal medicine by ICP-AES].

A new method has been developed for simultaneous derermination of 16 elements in decoction solution of Chinese herbal medicine by ICP-AES after pretreatrment the solution with HNO3-H2O2. This method has low and stable blank value. The detection limits of 0.1-5ng/ml for most elements and recoveries of 85-103% were obtained. This method has been applied to the determination of 16 elements in decoction solution of chinese herbal medicine with satisfactory reswls.

Analytic Sample Preparation Methods↗

Nativity, race, and mortality: influence of region of birth on mortality of US-born residents of New York City.

Among non-Hispanic black and white residents of New York City the association between birthplace by region (South, West/ Midwest, and Northeast) within the United States and mortality was determined by linking mortality records for 1988-1992 with the 1990 United States census data for New York City. Age-adjusted death rates computed by birthplace for blacks and whites were examined and also compared with total US data. The results indicate that death rates for New Yorkers generally exceed those of the United States overall, and black rates exceed those of whites. Moreover, Southern-born blacks have substantially higher death rates than do blacks born in the Northeast. The most striking variations are for cancer and diseases of the heart. Deaths from AIDS and homicide are higher among blacks than among whites, but the rates for Southern-born blacks do not exceed those for Northeastern-born blacks. For whites those born in the South have higher death rates overall than those born in the Northeast, but differences in cause-specific mortality are less consistent than for blacks. The results reveal substantial heterogeneity of health status based on nativity, among blacks in particular. To understand the role of the related factors, both genetic and environmental, further population and epidemiologic studies are important.

Adult↗

Pathogenesis and prevention of HTLV-1-associated diseases.

HTLV-1 is an important factor involved in various diseases including adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. Amount of HTLV-1 provirus integrated in human peripheral blood mononuclear cells might be a candidate for a risk factor in the manifestation of HTLV-1 associated diseases. Experimental animal models would be useful to dissect the pathogenesis of HTLV-1 associated diseases. We present rat and mouse models of HTLV-1 infection. Using these animal models, we could clarify the intrauterine transmission of HTLV-1, and have found that both genetic background and HTLV-1 infection are important in pathogenesis of HAM/TSP-like rats. We also discuss the preventive measures of HTLV-1 transmission by use of antisense oligonucleotides.

Adult↗

Establishment of HTLV-1 carrier mice by injection with HTLV-1-producing T cells.

We injected with HTLV-1-producing T-cells, MT-2, into C3H/HeJ and Balb/c mice intraperitoneally within 24 hours after birth and at one week old. At 3 months old, HTLV-1 provirus was detected in peripheral blood mononuclear cells in both mice. It was also detected in lymph nodes, thymus, spleen and liver of those mice. The antibody response against HTLV-1 Gag antigen was detected in some of Balb/c mice. These findings suggest that the C3H/HeJ and Balb/c mice were infected with HTLV-1 persistently. The HTLV-1-infected mice should be helpful for studying the pathological state of HTLV-1 carriers and for an establishment of a small animal model of HTLV-1 related diseases including ATL.

Animals↗

The influence of birthplace on mortality among Hispanic residents of New York City.

To determine the mortality experience of Hispanic residents of New York City and the influence of birthplace on their mortality rates, NYC Department of Health mortality records for 1988 to 1992 were linked for analysis with 1990 United States census data for New York City. Age-specific death rates for all Hispanics were compared by birthplace with those of non-Hispanic whites. Age-adjusted death rates were also compared. Overall, Hispanics had death rates lower than non-Hispanic blacks, and death rates similar to those of non-Hispanic whites. Hispanics had higher rates of death from HIV-infection, diabetes, stroke/hypertensive disease, cirrhosis and homicide, and fewer deaths from cancer and coronary heart disease than did non-Hispanic whites. Moreover, there were substantial differences in mortality between Hispanic subgroups categorized by birthplace. Migrants from Puerto Rico had the highest, and those from Central and South America the lowest mortality rates. United States-born Hispanics, although younger, had age-adjusted mortality rates higher than New York City non-Hispanic whites. In summary, the mortality of Hispanics generally approximated that of non-Hispanic whites, and was lower than that of non-Hispanic blacks. However, stratification of Hispanics by birthplace revealed substantial variation within the Hispanic population of New York City.

Adolescent↗

Nativity, race, and mortality: favorable impact of birth outside the United States on mortality in New York City.

To determine the association of birthplace (US-born vs. foreign-born) with mortality among blacks and whites in New York City, we examined death records for 5 years from 1988 to 1992 and the 1990 census data. Mortality rates by race and birthplace were compared for all causes of death and for specific causes. Although overall death rates for blacks generally exceeded those for whites (1224.8 per 100,000 inhabitants vs. 721.4 for males and 593.7 vs. 393.1 for females), foreign-born blacks had death rates (664.6 for males and 350.2 for females) slightly lower than those for whites. The most striking variation among blacks was among those aged 25 to 64 years. US-born black males were three times as likely (1588.9 vs. 525.2) and US-born black females were more than 2.5 times as likely (673.5 vs. 263.4) to die as were foreign-born blacks. Among US-born blacks AIDS, homicide, and cancer for males and AIDS, heart disease, and cancer for females were the most important determinants of excess deaths, defined as the difference between observed deaths and expected deaths; these causes of death account for about half of the excess deaths for each sex. Among whites natives generally had higher death rates than migrants, but less prominently and consistently so than for blacks. Excess mortality of blacks is largely explained by higher death rates of US-born compared with foreign-born Americans.

Adolescent↗

Effects of a quaternary pyridinium metabolite of haloperidol (HP+) on the viability and catecholamine levels of cultured PC12 cells.

Haloperidol has been found to be metabolized to a pyridinium ion (HP+; 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium). HP+ is structurally similar to the toxic metabolite of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), N-methyl-4-phenylpyridinium (MPP+). HP+ is toxic towards dopaminergic neurons and was proposed to be associated with some of the extrapyramidal side effects of haloperidol. We therefore investigated the neurotoxicity of HP+ towards cultured PC12 cells. At high concentrations, HP+ reduced the viability of PC12 cells as measured by trypan blue exclusion and the MTT method. However, HP+ decreased intracellular dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and dihydroxyphenylalanine (DOPA) levels at lower concentrations than those required to compromise cell viability. The immunoreactivity of tyrosine hydroxylase was not affected by the treatment with HP+. It was subsequently demonstrated that HP+ can release [3H]DA preloaded in rat striatum slices. Thus, it is proposed that HP+ decreases dopamine content in PC12 cells through actively releasing amines from the cells and (or) blocking the reuptake of the released amines.

Animals↗

Extremely low awareness of AIDS, sexually transmitted diseases and condoms among Dai ethnic villagers in Yunnan province, China.

OBJECTIVE: To assess the awareness of AIDS, other sexually transmitted diseases (STDs), condoms, sources of health information and HIV-related societal risks among Dai villagers in southern Yunnan Province, China. SUBJECTS AND METHODS: In November-December 1994, a cross-sectional descriptive study, comprising a questionnaire-based survey and focus group discussions, was conducted in three Dai villages in Mengla county; a total of 177 Dai villagers were interviewed in the survey and eight focus group discussions were held. Ethnographic observations provided a composite picture of HIV risks in the area. RESULTS: Only 18% of respondents had heard of AIDS, and only 25 and 28%, respectively, had heard of STDs or condoms. Furthermore, among these more aware groups, the level of knowledge was low and misconceptions were common. An ability to understand the official language (Mandarin) was the most important predictor of awareness of AIDS, other STDs or condoms. The sources of information in the three Dai villages sampled included TV, videos, radio and magazines, but only TV and videos had a large audience. Even so, these media were mostly in Mandarin and were not used in AIDS education. Travel outside of China was frequent; most villagers (77%) had traveled to Laos and 9% had traveled to Thailand. Societal risks of HIV transmission, such as an increasing incidence of STDs and an active sex industry, were observed in this area. CONCLUSIONS: Dai villagers in southern Yunnan Province had an extremely low awareness and knowledge of AIDS, other STDs and condoms. Given the high mobility of ethnic villagers to neighboring countries in Southeast Asia and the societal risks of HIV transmission in this area, there is an urgent need to provide accessible education about AIDS and other STDs. Suggestions regarding such health education and the implications of HIV policy-making are discussed.

Acquired Immunodeficiency Syndrome↗

[The spontaneous otitis media in rickety rats].

This paper is aimed to study the incidence and hearing impairment of spontaneous otitis media in rickety rats during a longterm vitamin D deficient breeding. Thirty Sprague-Dawley rats ranged from 20 to 25-day-old were used, and vitamin D deficient rickets models were established. Another thirty rats were used as the normal control. It was found that both normal and rickety rats had the possibilities of suffering from otitis media (mainly exudative) during the two-month-breeding. The incidence of otitis media in normal rats was 5% (3 from 60 ears), while that in the rickety ones was 16.67% (10 from 60 ears). It is believed that a rickety sufferer may be in higher danger of having otitis media than the normal one.

Action Potentials↗

In vitro differentiation potential of the periosteal cells from a membrane bone, the quadratojugal of the embryonic chick.

The quadratojugal (QJ) is a neural crest-derived membrane bone in the maxillary region of the avian head. In vivo its periosteum undergoes both osteogenesis to form membrane bone and chondrogenesis to form secondary cartilage. This bipotential property, which also exists in some other membrane bones, is poorly understood. The present study used cell culture to investigate the differentiation potential of QJ periosteal cells. Three cell populations were enzymatically released from QJ periostea and plated at different densities. Cell density greatly affected phenotypic expression and differentiation pathways. We found two culture conditions that favored osteogenesis and chondrogenesis, respectively. In micromass culture, the periosteal cells produced a layer of osteogenic cells that expressed alkaline phosphatase (APase) and secreted bony extracellular matrix (ECM). In contrast, low-density monolayer culture elicited chondrogenesis. Cells with pericellular refractile ECM and round shape appeared at 7 to 8 days and formed colonies later. The chondrogenic phenotype of these cells was confirmed by immunolocalization of type II collagen and Alcian blue staining of ECM. This result demonstrated that a fully expressed chondrogenic phenotype can be achieved from membrane bone periosteal cells in primary monolayer culture. Chondrogenesis requires a cell density lower than confluence and cannot be initiated in confluent cultures. Among the three cell populations, those cells from the outer layer have the highest growth rate and require the lowest initial plating density (below 5 x 10(3) cells/ml) to achieve chondrogenesis. Cells from the inner layer have the slowest growth rate and chondrify at the highest initial density (below 5 x 10(4) cells/ml). Chondrocytes from all populations express distinct phenotypic markers-APase and type I collagen-from initial chondrogenesis, but are not hypertrophic morphologically. Furthermore, the fact that chondrocytes arise within the same colony as APase-positive polygonal cells suggests that chondrocytes may differentiate from precursors related to the osteogenic cell lineage. This cell culture approach mimics secondary cartilage and membrane bone formation in vivo.

Alkaline Phosphatase↗

Non-rapid eye movement sleep is suppressed in transgenic mice with a deficiency in the somatotropic system.

Sleep-wake activity was studied in a transgenic mouse model (TH-hGH) with a deficiency in the somatotropic axis (growth hormone (GH)-releasing hormone (GHRH)-GH-insulin-like growth factor-I (IGF-I)). This dwarf transgenic mouse strain expresses a human GH (hGH) reporter gene linked to 4.8 kb of the rat tyrosine hydroxylase flanking sequence, targeting the production of hGH to sites of tyrosine hydroxylase synthesis in the brain. Endogenous GH and IGF-I are suppressed in these mice, as well as GHRH. Sleep-wake activity (EEG and EMG) was recorded for 2 to 3 days in nine transgenic mice and nine wild-type littermates. Non-rapid eye movement sleep (NREMS) was significantly suppressed during both the light and the dark period in the transgenic mice; rapid eye movement sleep (REMS) was not altered. The results provide evidence that the somatotropic axis contributes to normal sleep regulation.

Animals↗

Molecular cloning of the mouse activin beta E subunit gene.

cDNA clones encoding a novel activin beta subunit have been isolated from mouse liver cDNA library. An amino acid homology comparison among members of the TGF-beta superfamily indicates that the open reading frame codes for a new activin/inhibin beta subunit. The predicted mature region of the subunit shows > 60% identity with activin beta C and beta D and > or = 45% identity with activin beta A and beta B, but only 20-40% amino acid sequence identity with other TGF-beta superfamily members. Therefore, the novel subunit has been designated activin beta E. Alignment of the mature growth factor region of the five activin beta subunits revealed that activin beta A and beta B share 63% amino acid identity, while activin beta C, beta D, and beta E share 62% identity. Therefore, activin beta A and beta B are most related to one another, while activin beta C, beta D, and beta E may represent a subset of related sequences.

Activins↗