Biomedical subjects

S Mu

Publications and source records attributed to S Mu.

12 recordsLinked to original sources

PubMed2004

Bidirectional on/off switch for controlled targeting of proteins to subcellular compartments.

A regulatable fusion protein was constructed for controlling the localization of plasmid products. A ligand-inducible nuclear localization signal, nuclear export signal (NES) and a truncated form of the ligand binding domain of the progesterone receptor were attached to the desired protein. Enhanced green fluorescent protein (EGFP) was used as a model protein and its trafficking between the nucleus and cytoplasm was studied using fluorescence microscopy in response to the ligand, mifepristone. It was found that the protein trafficking into the nucleus was dose dependent with ligand concentration. Increasing the ligand dose from 1 to 100 nM enhanced import and reduced the rate of export of the fusion protein from the nucleus to the cytoplasm. This study demonstrates the feasibility of using an export signal and a ligand-inducible nuclear import signal as a bi-directional on/off switch with potential use for controlled targeting of therapeutic proteins to subcellular compartments.

Animals↗

PubMed2003

Asbestos related diseases from environmental exposure to crocidolite in Da-yao, China. I. Review of exposure and epidemiological data.

BACKGROUND: Scattered patches of crocidolite, one form of asbestos, were found in the surface soil in the rural county of Da-yao in southwestern China. In 1983, researchers from the West China University of Medical Sciences (WCUMS) discovered that residents of two villages in Da-yao had hyperendemic pleural plaques and excessive numbers of pleural mesotheliomas. AIMS: To review and summarise epidemiological studies, along with other relevant data, and to discuss the potential contribution to environmental risk assessment. METHODS: This report is based on a review of several clinical/epidemiological studies conducted by WCUMS researchers since 1984, which included one cross sectional medical examination survey, one clinical/pathological analysis of 46 cases of mesothelioma, and three retrospective cohort mortality studies. Additional information acquired from reviewing original data first hand during a personal visit along with an interview of medical specialists from Da-yao County Hospital was also incorporated. RESULTS: The prevalence of pleural plaque was 20% among peasants in Da-yao over 40 years of age in the cross sectional survey. The average number of mesothelioma cases was 6.6 per year in the 1984-95 period and 22 per year in the 1996-99 period, in a population of 68 000. For those mesothelioma cases that were histology confirmed, there were 3.8 cases/year in the first period and 9 cases/year in the second. Of the 2175 peasants in this survey, 16 had asbestosis. Lung cancer deaths were significantly increased in all three cohort studies. The annual mortality rate for mesothelioma was 85 per million, 178 per million, and 365 per million for the three cohort studies, respectively. The higher exposed peasants had a fivefold increased mesothelioma mortality compared to their lower exposed counterparts. There were no cases of mesothelioma in the comparison groups where no crocidolite was known to exist in the environment. In the third cohort study, almost one of five cancer deaths (22%) was from mesothelioma. The ratio of lung cancer to mesothelioma deaths was low for all three studies (1.3, 3.0, and 1.2, respectively). CONCLUSIONS: The observation of numerous mesothelioma cases at Da-yao was a unique finding, due mainly to their lifetime exposure to crocidolite asbestos. The finding of cases dying at a younger age and the relatively high ratio of mesothelioma cases to lung cancer could also be another unique result of lifetime environmental exposure to crocidolite asbestos. Although the commercial use of crocidolite has been officially banned since 1984, the incidence of mesothelioma has continued to show a steady increase, particularly among peasants. Since the latency of mesothelioma is approximately 30-40 years, the ban had little effect in the 1990s. The increased awareness and changes in diagnosis over time may also contribute to the increase. Furthermore, exposure to asbestos stoves and walls continued. The government implemented reduction of these exposures. However, from a public health standpoint, the most important issue is the complete avoidance of further exposure to asbestos.

Asbestos, Crocidolite↗

PubMed2001

WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection.

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors. The physiological role of WSX-1, which is expressed mainly in T cells, was investigated in gene-targeted WSX-1-deficient mice. IFN-gamma production was reduced in isolated WSX-1(-/-) T cells subjected to primary stimulation in vitro to induce Th1 differentiation but was normal in fully differentiated and activated WSX-1(-/-) Th1 cells that had received secondary stimulation. WSX-1(-/-) mice were remarkably susceptible to Leishmania major infection, showing impaired IFN-gamma production early in the infection. However, IFN-gamma production during the later phases of the infection was not impaired in the knockout. WSX-1(-/-) mice also showed poorly differentiated granulomas with dispersed accumulations of mononuclear cells when infected with bacillus Calmette-Guerin (BCG). Thus, WSX-1 is essential for the initial mounting of Th1 responses but dispensable for their maintenance.

Animals↗

PubMed2000

[Acoustic densitometry for quantification of renal allografts microcirculation and microstructure].

OBJECTIVE: To establish a new method for observing renal allografts microcirculation and microstructure with acoustic densitometry (integrated backscatter, contrast, second harmonics). METHODS: 27 patients with renal allografts were investigated by Doppler, IBS, contrast and second harmonics. Renal allografts failed age in 5 patients 20-61 years. Intravenous injection of SHU-508A was given, compared with pre-injection by quantitative assessment of acoustic densitometry (AD) of renal microstructure. RESULTS: There was a significant difference in the peak intensity, the area under the curve and the half-time of wash-out between pre-injection and injection contrast agent. The wish-in and wish-out curve was shown in a peak shape. The renal allografts with acute rejection were significantly lower than the control group in AD (P < 0.05). No contrast opacification of renal microstructure was present in 5 failed renal allografts and the wish-in and wish-out curve appeared in a straight line shape. CONCLUSION: AD is safe, and efficient in assessing renal allografts microstructure. It more sensitive in detecting allograft complication such as rejection than Doppler.

Adult↗

PubMed2000

[Effects on fiber regeneration following facial nerve transection treated with NOS antagonist].

OBJECTIVE: To elucidate the role of nitric oxide synthase antagonist, N-Nitro-L-Arginine Methyl Ester (L-NAME) in the regeneration of facial nerve following facial nerve transection. METHOD: The facial nerves of 40 guinea pigs were exposed and a segment of the nerve at 3 mm length were excided. The two ends of the transected nerve were sutured and enveloped in a silicone tubule to form a regeneration chamber. L-NAME and saline were respectively injected into the regeneration chambers just after transection. The experiments were observed quantificational by the means of axon and myelin staining under light microscope. RESULT: The findings in the work indicate that inhibition of NOS with L-NAME substantially better myelinated facial nerve regeneration than that associated with administration of saline. CONCLUSION: L-NAME improve the regeneration of myelinated fibers. The mechanism seems to be related to the blockade of NO's neurotoxicity.

Animals↗

PubMed1999

Ectopic overexpression of c-mpl by retroviral-mediated gene transfer suppressed megakaryopoiesis but enhanced erythropoiesis in mice.

In this report, we tested whether ectopic overexpression of a cell surface receptor cDNA could be used to explore the physiological roles of that receptor. We generated c-mpl overexpressing animals by reconstituting mice with retroviral vector-transduced bone marrow (BM) cells. We observed that platelet counts in the c-mpl overexpressing mice failed to recover to normal levels and remained at <200 x 10(6)/mL post-transplantation, while platelet numbers in the control mice returned to > 800 x 10(6)/mL by 4 weeks post-transplantation. However, platelet counts in the c-mpl overexpressing mice could be stimulated to normal levels after administration of rhMGDF. No significant changes in peripheral leukocyte counts were observed, although the number of CFU-E, GM-CFC, and CFC-multi were reduced two- to threefold in the BM of the c-mpl overexpressing mice. In addition, enhanced erythropoiesis was observed in the c-mpl overexpressing mice. The mpl receptors on erythroid cells were functional as demonstrated by tyrosine-phosphorylation of mpl receptor on RBC and by in vitro erythroid colony-formation in response to MGDF stimulation, respectively. These results suggested that ectopically expressed mpl receptors competed for ligand in vivo leading to an insufficient amount of circulating thrombopoietin (Tpo) for the development of megakaryocytic lineage. These results further suggest that, in addition to sequestering circulating Tpo, overexpression of the mpl receptor on erythroid progenitors may directly contribute to enhanced erythropoiesis in vivo. Our studies demonstrate that ectopic overexpression of a receptor by retroviral-mediated gene transfer provides an approach to explore the biological roles of novel receptors.

Animals↗

PubMed1998

[The risk of lung cancer and mesothelioma in farmers exposed to crocidolite in environment].

To assess the risk of lung cancer and mesothelioma after environmental exposure to crocidolite for 20-30 years, a retrospective cohort study was carried out in farmers who had been exposed to crocidolite in environment. 1610 subjects were followed up for 9 years (Jan. 1, 1987 Dec. 31, 1995). The control group consisted of 7646 farmers who resided in the noncrocidolite pollution rural area in the same province. The results showed that the annual mortality rate was 43.75 per 100,000 population for lung cancer, and 36.46 per 100,000 for mesothelioma. Significantly high risks of lung cancer (RR 5.67) and mesothelioma (RR 182.3) were noted. These results demonstrate a strong causal association between lung cancer, mesothelioma and exposure to crocidolite.

Adult↗

PubMed1998

[Investigation and analysis of the diagnostic status of bronchial asthma].

OBJECTIVE: The aim of this study was to investigate the rate of delayed diagnosis of the bronchial asthma and related factors. METHOD: 57 asthmatic outpatients were investigated randomly by questionnaire including main symptoms of asthmatic attack, the date of initial attack, the date of initial visit physician, and initial diagnosis, the basis of diagnosis and the names of misdiagnosed diseases. Then according to the above-mentioned data the duration of delayed diagnosis, the rate of delayed diagnosis were calculated. RESULT: 96% of outpatients saw physician within 1 yr. after initial attack. The duration from initial visit to making diagnosis were 11.1 +/- 2.3, and 1.5 +/- 0.3 yr. before and after 1980, respectively, and their rate of delayed diagnosis were 75%, 15%, respectively. Both of their differences were statistically significant (P < 0.01). Only 20% of diagnosis of asthma was by pulmonary function test. CONCLUSION: The majority of the delayed diagnosis should be due to making the mis-understanding and underattention of physician to the asthma, and their diagnostic levels should need further improving.

Adult↗

PubMed1995

Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice.

Megakaryocyte growth and development factor (MGDF) has recently been identified as a ligand for the c-mpl receptor. Using retroviral-mediated gene transfer, MGDF has been overexpressed in mice to evaluate the systematic effects due to chronic exposure to this growth factor. MGDF overexpressing mice had more rapid platelet recovery than control mice after transplantation. Following this recovery, the platelet levels continued increasing to fourfold to eightfold above normal baseline levels and remained elevated (five-fold above control mice) in these animals, which are alive and well at more than 4 months posttransplantation. Increased megakaryocyte numbers were detected in a number of organs in these mice including bone marrow, spleen, liver, and lymph nodes. Prolonged overexpression of MGDF led to decreased marrow hematopoiesis, especially erythropoiesis, with a shift to extramedullary hematopoiesis in the spleen and liver. All the MGDF overexpressing mice analyzed to date developed myelofibrosis and osteosclerosis, possibly induced by megakaryocyte and platelet produced cytokines. No significant effect on other hematopoietic lineages was seen in the MGDF overexpressing mice, showing that the stimulatory effect of MGDF in vivo is restricted to the megakaryocyte lineage.

Animals↗

PubMed1994

The tsA58 simian virus 40 large tumor antigen disrupts megakaryocyte differentiation in transgenic mice.

Thrombocytopenia is a condition of multiple etiologies affecting the megakaryocyte lineage. To perturb this lineage in transgenic mice, the tsA58 mutation of the simian virus 40 large tumor antigen was targeted to megakaryocytes using the platelet factor 4 promoter. Ten of 17 transgenic lines generated exhibited low platelet levels, each line displaying a distinct, heritable level of thrombocytopenia. Within a line, the degree of the platelet reduction correlated directly with transgene zygosity. The platelet level could be further reduced by the inactivation of one copy of the endogenous retinoblastoma gene. Western blot analysis detected large tumor antigen protein in the most severely affected lines; less affected lines were below the level of detection. Platelets and megakaryocytes from thrombocytopenic mice exhibited morphological abnormalities. Mice with either normal or reduced platelet levels developed megakaryocytic malignancies with a mean age of onset of about 8 months. There was no correlation between severity of thrombocytopenia and onset of malignancy. These mice provide a defined genetic model for thrombocytopenia, and for megakaryocytic neoplasia, and implicate the retinoblastoma protein in the process of megakaryocyte differentiation.

Animals↗

PubMed1993

Purification and properties of a diisopropyl-fluorophosphatase from squid Todarodes pacificus steenstrup.

A diisopropyl-fluorophosphatase (DFPase) was purified from brain and ganglia of squid Todarodes pacificus steenstrup. The DFPase had a preference in hydrolysis toward diisopropylphosphorofluoridate (DFP). It also was able to hydrolyze O-1,2,2-trimethylpropyl methylphosphofluoridate (soman) and O-isopropyl methylphosphonofluoridate (sarin) at nearly equal hydrolytic rates but only 1/10 that of DFP. The hydrolytic activity toward diethyl-p-nitrophenylphosphate (paraoxon) was very low compared with DFP, soman, and sarin. The DFPase was purified 330-fold to a specific activity of 18,300 n mol/min/mg protein. Its molecular weight was 34,000 dalton determined by gel-filtration chromatography. Mn2+ stimulation of the DFPase was not observed when DFP and soman were the substrates, but with sarin, the rate increased onefold in the presence of 1.0 mM of Mn2+. Ethylenediamine tetraacetic acid disodium (EDTA-Na2) at 0.05 M inhibited the DFPase activity about 30%. It could be concluded that this DFPase belongs to the squid-type DFPase.

Animals↗

PubMed1991

[Study on relationship between human ABO blood groups and type A behavior pattern].

Investigation of the relationship between ABO blood groups (ABO BG) and Type A behavior pattern (TABP) was performed. No significant correlation was found between human ABO BG and TABP (P less than 0.05). However, CH and TH + CH scores in individuals with blood type A and type A personality were significantly lower (P less than 0.05). The values of TH-CH scores among tested people were of no statistical significance (P greater than 0.05). Moreover, nearly half of the examinees (41.32%) had higher CH score and the distribution of the individuals was obviously different in statistics (P less than 0.005). In addition, L score of examinees with blood type A and type B personality was relatively lower.

ABO Blood-Group System↗