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Biomedical subjects

G Li

Publications and source records attributed to G Li.

At least 721 records · Page 40Linked to original sources

Failure to detect human T-lymphotropic virus type-I proviral DNA in cell lines and tissues from patients with cutaneous T-cell lymphoma.

Previous molecular studies investigating the presence of HTLV-I proviral DNA in cell lines and tissue samples of patients with cutaneous T-cell lymphoma (CTCL) have reported a detection rate ranging from 0-92%. Despite the lack of epidemiologic data linking HTLV-I infection with CTCL, the molecular data still invite speculation regarding the precise role of HTLV-I in the pathogenesis of CTCL. To determine the detection rate of HTLV-I proviral DNA among CTCL patients referred to our medical center, we analyzed Epstein-Barr virus-transformed cell lines established from peripheral blood of seven CTCL patients and 43 tissue samples from 22 patients with different stages of disease. Genomic DNA was polymerase chain reaction-amplified with primers within the HTLV-I tax gene region. Amplification products were probed with nested oligonucleotide probes by Southern blot analysis. No HTLV-I proviral sequences were detected in the samples (0/50). Using HTLV-I/II pol primers, no HTLV-I pol gene sequences were detected. In tissues from one patient, HTLV-II pol and tax gene sequences were detected; however, HTLV-II proviral integration was not detected by Southern blot analysis of the genomic DNA. Our data suggest: (i) HTLV-I does not appear to be a primary etiologic agent in CTCL; and (ii) HTLV-II pol and tax gene sequences can be detected in a minority of CTCL patients, but this does not necessarily imply an etiologic role.

Base Sequence↗

A comparative analysis of alcohol in fatal and nonfatal bicycling injuries.

Bicycling is the leading cause of recreational injury, resulting in more than half a million emergency department visits and about 900 deaths each year in the United States. Previous research on bicycling injury was conducted predominantly in children and focused on the effectiveness of safety helmets. Few studies have examined the role of alcohol in bicycling injuries. This study examined the magnitude of and factors related to alcohol involvement in fatal and nonfatal bicycling injuries, and tested the hypothesis that alcohol intoxication is associated with significantly increased likelihood of fatality given a serious bicycling injury. Medical examiner data on all fatally injured bicyclists aged 10 years or older from 1987 to 1994 in Maryland (fatal cases, n = 63) were compared with trauma registry data on all injured bicyclists who were treated at a regional trauma center during the same time period (nonfatal cases, n = 253) on variables related to blood alcohol concentrations (BACs), demographic characteristics, and injury circumstances. The fatal cases were more likely than the nonfatal cases to have positive BACs (30% vs. 16%, p < 0.01) and to be legally intoxicated (i.e., BACs > or = 0.10%) (22% vs. 13%, p < 0.01). For both fatal and nonfatal cases, intoxication was more prevalent among victims who were male, aged 20 to 39 years, or who were injured at nighttime (7:00 PM to 6:59 AM). Bicyclists who died at the scene were four times as likely as those who died at hospitals to be legally intoxicated (35% vs. 9%, p < 0.02). Given a serious bicycling injury, intoxication was associated with significantly increased likelihood of fatality, with an adjusted odds ratio of 2.8 (95% confidence interval, 1.3 to 6.3). This increased likelihood of fatality was probably due in part to the fact that the rate of helmet use at the time of injury among the intoxicated was much lower than among the sober (6% vs. 31%, p < 0.05). Results indicate that alcohol plays an important role in fatal and serious bicycling injuries. Preventing intoxicated biking should be incorporated into helmet campaigns and other bicycle safety programs.

Accidents, Traffic↗

Interference to human immunodeficiency virus type 1 infection in the absence of downmodulation of the principal virus receptor, CD4.

It is thought that interference during human immunodeficiency virus type 1 (HIV-1) infection is established by downmodulation of the principal virus receptor, CD4. Here we present evidence to the contrary. At various times after primary infection, we superinfected T cells in vitro by exposure to a genetically distinct viral clone or to a virus carrying the chloramphenicol acetyltransferase gene. Replication of each virus strain was determined by restriction enzyme analysis of total cellular DNA, by PCR amplification of viral DNA, or by assay of cell extracts for chloramphenicol acetyltransferase activity. We found that efficient viral interference is established within 24 h of infection at a multiplicity of infection of 1. At that time, expression of viral structural proteins was low and infected cells displayed undiminished levels of surface CD4 and were fully susceptible to virus binding and fusion. Superinfection by either cell-free HIV-1 or cocultivation was blocked. Cells resistant to superinfection by HIV-1 remained susceptible to Moloney murine leukemia and vaccinia viruses. No interference was observed 4 h after primary infection or in cells infected with either UV-inactivated HIV-1 or a mutant virus defective in virus-cell fusion activity, indicating that binding of primary virus to CD4 is insufficient to prevent superinfection. The minimum viral requirements for this interference are that HIV-1 must be able to enter cells and synthesize viral DNA; Tat-mediated transcription is dispensable. Our results support the existence of a novel pathway to interference to HIV-1 infection, which we term postentry interference, which blocks superinfection during intracellular phases of the virus life cycle.

Base Sequence↗

Effect of a glucokinase inhibitor on energy production and insulin release in pancreatic islets.

Glucokinase has exclusively high control strength on glucose usage in the pancreatic beta-cell. However, glucokinase also has extraordinarily high control strength on insulin secretion, which is linked to the phosphate potential, [ATP]/([ADP][Pi]) (F.M. Matschinsky, Y.Liang, P. Kesavan, L. Wang, P. Froguel, G. Velho, D. Cohen, M.A. Permutt, Y. Tanizawa, T.L. Jetton, K. Niswender, and M.A. Magnuson. J. Clin. Invest. 92: 2092-2098, 1993). We propose that the ATP produced via the tricarboxylic acid cycle is approximately constant, irrespective of the glucose level. Furthermore, the component of ATP production that is derived from glycolysis and glycolytically derived NADH, which is shuttled into the mitochondria, is a critical signal controlling the ionic events leading to insulin secretion, as suggested previously (M. J. MacDonald. Diabetes 39: 1461-1466, 1990 and I.D. Dukes, M.S. McIntyre, R.J. Mertz, L.H. Philipson, M.W. Roe, B. Spencer, and J.F. Worley III. J. Biol. Chem. 269: 10979-10982, 1994). To test this hypothesis, glucose usage, oxidation, and insulin secretion were measured in cultured rat islets over a wide range of concentrations of glucose and mannoheptulose, an inhibitor of glucokinase. These data were fit to a mathematical model that predicts that glucokinase will govern the rate of glucose usage and ATP production and will also have a strong, but not complete, control over the rate of glucose oxidation, the phosphate potential, and insulin release. Mannoheptulose caused an inhibition of all three fluxes. The estimates of the mechanistic parameters of the model [maximal velocity (Vmax) and Michaelis constant for glucokinase, Vmax for hexokinase and glucose transport, and the inhibition constant of mannoheptulose to glucokinase] were similar to those obtained in vitro. Thus the data are consistent with a model in which the primary importance of glycolysis in transducing the glucose signal into changes of the phosphate potential imparts to glucokinase a high control strength on glucose-induced insulin secretion.

Animals↗

Interphase cytogenetics of workers exposed to benzene.

Fluorescence in situ hybridization (FISH) is a powerful new technique that allows numerical chromosome aberrations (aneuploidy) to be detected in interphase cells. In previous studies, FISH has been used to demonstrate that the benzene metabolites hydroquinone and 1,2,4-benzenetriol induce aneuploidy of chromosomes 7 and 9 in cultures of human cells. In the present study, we used an interphase FISH procedure to perform cytogenetic analyses on the blood cells of 43 workers exposed to benzene (median = 31 ppm, 8-hr time-weighted average) and 44 matched controls from Shanghai, China. High benzene exposure (> 31 ppm, n = 22) increased the hyperdiploid frequency of chromosome 9 (p < 0.01), but lower exposure (< or = 31 ppm, n = 21) did not. Trisomy 9 was the major form of benzene-induced hyperdiploidy. The level of hyperploidy in exposed workers correlated with their urinary phenol level (r = 0.58, p < 0.0001), a measure of internal benzene dose. A significant correlation was also found between hyperdiploidy and decreased absolute lymphocyte count, an indicator of benzene hematotoxicity, in the exposed group (r = -0.44, p = 0.003) but not in controls (r = -0.09, p = 0.58). These results show that high benzene exposure induces aneuploidy of chromosome 9 in nondiseased individuals, with trisomy being the most prevalent form. They further highlight the usefulness of interphase cytogenetics and FISH for the rapid and sensitive detection of aneuploidy in exposed human populations.

Adult↗

Tissue distribution of DNA adducts and their persistence in blood of mice exposed to benzene.

Chemicals combine with DNA, resulting in DNA damage, which could initiate carcinogenesis. To study whether benzene or benzene metabolites bind to DNA, DNA adducts in various tissues and their persistence in leukocytes were examined using the 32P-postlabeling assay. LACA mice were dosed ip with benzene at 500 mg/kg bw twice for 5 days. Two additional spots of DNA adducts are formed in bone marrow cells, liver cells, and peripheral blood compared with control mice. The relative adduct labeling values are 10.39, 11.32, and 13.77 adducts x 10(-8) nucleotides in these tissues, respectively. DNA adducts in blood leukocytes were observed at 1, 4, 7, 14, and 21 days after exposure to benzene, but adduct levels decreased as a function of time. Relative adduct labeling of "adduct B" declined linearly but mildly, while "adduct C" displayed a stepwise decrease. The relative adduct labeling values of both these adducts at day 14 were 50% of those at day 1 after the last treatment. Both adducts were still detectable at day 21 after benzene exposure. These studies demonstrate that benzene could induce DNA adducts in bone marrow, liver, and white blood cells of mice dosed with benzene and that measurement of adducts in white blood cells may be useful as a biomarker to predict carcinogenic risk of benzene to workers exposed to benzene.

Animals↗

Catalytic asymmetric aminohydroxylation provides a short taxol side-chain synthesis.

The p-toluenesulfonamide derivate of the C-13 side-chain of taxol was prepared on a one third mole scale in a single step from methyl cinnamate. The process employed is catalytic asymmetric aminohydroxylation (catalytic AA). In the present case, there is no work-up other than filtration of the pure product which is insoluble in the reaction mixture. The sulfonamide protecting group is removed by acidic hydrolysis.

Cinnamates↗

Decreased DNA repair but normal apoptosis in ultraviolet-irradiated skin of p53-transgenic mice.

p53 tumor suppressor plays a vital role in the cellular responses to genotoxic stress. It is believed that p53 regulates the cell cycle by activating the G1 checkpoint after exposure to agents like ionizing radiation, ultraviolet (UV) radiation, or genotoxic chemicals. Recently, it is conjectured that p53 may have additional functions in DNA repair and apoptosis. Previously, we demonstrated that p53-transgenic mice that carry mutant alleles of a p53 gene developed twice as many skin tumors as control mice after UV exposure. To elucidate the molecular mechanisms of mutant p53 in skin cancers, we studied DNA repair efficiency and the rate of apoptosis in murine keratinocytes after UV irradiation. In this report, we show that mutant p53-transgenic mouse skin has reduced repair of UV-induced DNA damage in both in vivo and in vitro radioimmunoassays. In control mice, DNA repair is associated with increased amounts of wild-type P53 protein. Unexpectedly, mutant p53-transgenic mice had slightly increased apoptosis after UV irradiation, suggesting that the wild-type p53 protein in the cells still functions in inducing apoptosis, or that this cell death results from p53-independent mechanisms. These results suggest that mutant p53 interferes with wild-type p53 in the repair of UV-induced DNA damage but not in apoptosis.

Animals↗

The epidemiology of aircraft fire in commuter and air taxi crashes.

BACKGROUND: Aircraft fire is recognized as an important risk factor for occupant fatality in aviation crashes, but its epidemiology has not been adequately studied. OBJECTIVE: This study examines factors related to the occurrence of aircraft fire, ignition sources, and factors influencing rescue and firefighting in commuter and air taxi crashes. METHODS: Commuter and air taxi crashes in 1983-88 that involved aircraft fire were analyzed using National Transportation Safety Board (NTSB) data, including NTSB supplemental forms on fire and on rescue and firefighting. RESULTS: Aircraft fire was recorded in 17% of the 888 commuter and air taxi crashes. Factors associated with increased likelihood of fire in these crashes were non-airport location (adjusted relative risk 2.7, 95% confidence interval 1.8-4.1), twin-engine aircraft (RR 2.5, 95% Cl 1.6-3.9), and nighttime (RR 1.7, 95% Cl 1.1-2.5). Fire was more common in Beech 18's than other twin-engine airplanes. The majority (59%) of fires occurred during impact sequence, and an additional 17% occurred after the aircraft came to rest. The engine was identified as the ignition source in 59% of the crashes, followed by hot surface (18%), short circuit (9%), and sparks (9%). Fire sensing and extinguishing systems were installed in only 19% of the aircraft. Rescue and firefighting efforts were hampered most commonly by terrain (48%), weather (47%), and darkness (38%). CONCLUSIONS: Typically induced by impact and started at the engine, aircraft fire is most likely when a crash occurs at night, in a non-airport location, and in instrument meteorological conditions. These high-risk circumstances also often thwart rescue and firefighting efforts.

Accidents, Aviation↗

[Detection of point mutation of p53 gene by silver staining PCR-SSCP in paraffin-embedded malignant fibrous histiocytoma].

Silver staining PCR-SSCP method was used to detect point mutation of p53 gene in paraffin-embedded malignant fibrous histiocytoma (MFH) tissues. The abnormal shifting of the single-stranded DNA (ssDNA) was identified in 9 out of 16 cases. The positive figure of SSCP was 1,4,4, 3 in exon 5, 6, 7, 8, respectively. The mutant p53 protein was detected by microwave oven treatment and ABC immunohistochemistry. Positive nuclear staining was observed in 10 cases. The positive coincidence rate was 90.0% between SSCP and p53 protein expression. The mutation of p53 gene was not correlated with the subtypes of MFH. Our results indicate that detection of point mutations with silver staining PCR-SSCP is convenient, rapid and reliable in the screening of point mutation of genes.

Genes, p53↗

Clinical investigation of traditional Chinese medicine and pharmacy in treating respiratory tract infections in AIDS.

Based on the difference in severity of the disease and complications, 80 cases of acquired immune-deficiency syndrome (AIDS) accompanied with cough were divided into 2 groups: One treated by traditional Chinese medicine (TCM group), including 58 cases and the other treated by Integrated Chinese and Western medicine (integrated group), 22 cases. The therapeutic results show that in the TCM group there were 18 cases (31.03%) with clinical cure of the respiratory tract infection, 7 cases with therapeutic effect (12.07%) and 33 cases without any effect (56.90%), for a total rate of 43.10% therapeutic effectiveness; while in the integrated group there were 6 cases with clinical cure (27.27%), 2 cases with therapeutic effect (9.09%) and 14 cases without any effect (63.64%), the total rate of therapeutic effectiveness being 36.36%, slightly lower than in the TCM group and possibly related to greater severity of the disease or complications.

Acquired Immunodeficiency Syndrome↗