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Biomedical subjects

J M Wu

Publications and source records attributed to J M Wu.

At least 55 records · Page 3Linked to original sources

Thermal physiological consideration of precooling procedures in manned space craft.

OBJECTIVE: To explore a space craft precooling temperature at which excessive thermal stress on the crew member could be prevented or reduced in an overheated launch or reentry module. METHOD: Five young male volunteers wearing a space suit participated in 25 tests at sea level. The space suit was either ventilated in a volume air flow rate of 100 L/min (STPD) with ambient air at temperatures (Ta) of 15 degrees C, 10 degrees C, and 5 degrees C, respectively, or not ventilated. Rectal (Tr), mean skin (Tsk) and mean body (Tb) temperatures were measured. RESULT: At Ta 15 degrees C, Tr decreased without significance (from 37.0 +/- 0.2C to 36.7 +/- 0.3 degrees C) in 120-min tests, whereas mean Tsk and mean Tb decreased significantly, and subjects had local cold strain whether the space suit was ventilated or not; while at Ta 10 degrees C, Tr decreased from 37.0 +/- 0.3 degrees C to 36.3 +/- 0.3 degrees C (P < 0.05), subjects had a whole body cold strain, and both mean Tsk and Tb dropped continuously and significantly. CONCLUSION: Ambient temperature 15 degrees C, at which the thermal comfort states of crew was not significantly degraded, was acceptable after precooling in a space craft.

Adolescent↗

Effects of resveratrol on oxidative modification of human low density lipoprotein.

OBJECTIVE: To determine the antioxidative effects of resveratrol (RES), a polyphenolic compound in red wine, on the oxidation of human low density lipoprotein (LDL) using two different oxidation systems. METHODS: Oxidation of LDL was induced by adding either Cu2+ or an azo compound. The extent of LDL modification was assessed by measuring the formation of thiobarbituric acid reactive substances (TBARS), the relative electrophoretic mobilities (REM), and the amount of oxidized LDL degradation by macrophages. RESULTS: During Cu(2+)-induced oxidation, RES reduced TBARS formation in LDL by 70.5%, REM of LDL by 42.3% and the amount of macrophage degradation by 65.7%, respectively. The lag phase of LDL oxidation was also delayed by adding RES both in the copper ion and azo compound-induced oxidation systems. CONCLUSION: RES can protect LDL against both Cu(2+)-induced and azo compound-initiated oxidative modification in vitro, which might be due to its free radical scavenging capacity.

Animals↗

Quantification of the human granulocytic ehrlichiosis agent based on analysis of rRNA isolated from control and infected HL-60 cells.

Human granulocytic ehrlichiosis (HGE) is an emerging vector-borne disease caused by an Ehrlichia species similar or identical to E. equi and E. phagocytophila. Previous studies have shown that the pathogen can be cultivated in vitro in permissive cells such as human promyelocytic HL-60 leukemia cells. The mechanism(s) of its infection and propagation in target cells, however, is not well understood, due in part to lack of a method capable of quantitatively determining the amount of the infectious agent. Although several assays currently exist for the HGE agent, they are mostly qualitative and have a number of limitations. In this report, size differences between prokaryotic and eukaryotic rRNAs are utilized to quantitatively assay the HGE agent in HL-60 cells. By comparing the integrated intensity of agarose gel resolved HGE-specific rRNA in host cells, with identically prepared and analyzed rRNA isolated from known quantities of E. coli (JM 109), it is possible to calculate the E. coli-equivalence of the HGE agent present in HL-60 cells according to the equation: Y (E. coli, in viable cells x 10(8)) = -2.573 + 0.11X (% infection by the HGE agent in HL-60 cells). The method described is reproducible, sensitive, and is not limited by availability of antisera. Furthermore, since the assay has no designer primer and repeated amplification requirements, it can be easily disseminated to and standardized in other laboratories.

Cell Count↗

Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2.

Epidemiological studies have shown that the regular consumption of red wine may in part account for the apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis. This phenomenon, commonly referred to as the French paradox, may be associated with red wine constituents that exhibit tumor-preventive properties as well as inhibit reactions that increase the risk of coronary heart disease. Here we show that resveratrol, a polyphenol in red wine, induces nitric oxide synthase, the enzyme responsible for the biosynthesis of NO, in cultured pulmonary artery endothelial cells, suggesting that resveratrol could afford cardioprotection by affecting the expression of nitric oxide synthase. We also show that resveratrol inhibits the proliferation of pulmonary artery endothelial cells, which, based on flow cytometric analysis, correlates with the suppression of cell progression through S and G2 phases of the cell cycle. Western blot analysis and immunocytochemical protein detection combined with multiparameter flow cytometry further demonstrate that the perturbed progression through S and G2 phases is accompanied by an increase in the expression of tumor suppressor gene protein p53 and elevation of the level of cyclin-dependent kinase inhibitor p21(WAF1/CIP1). All of the observed effects of resveratrol, including induction of apoptosis at its higher concentration, are also compatible with its putative chemopreventive and/or antitumor activity.

Animals↗

Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines.

Epidemiologic studies have suggested that nutrition plays an important role in carcinogenesis and that 30% of cancer morbidity and mortality can potentially be prevented with proper adjustment of diets. Resveratrol, a polyphenol present in red wines and a variety of human foods, has recently been reported to exhibit chemopreventive properties when tested in a mouse skin cancer model system. In this study, we investigated the effects of resveratrol on growth, induction of apoptosis, and modulation of prostate-specific gene expression using cultured prostate cancer cells that mimic the initial (hormone-sensitive) and advanced (hormone-refractory) stages of prostate carcinoma. Androgen-responsive LNCaP and androgen-nonresponsive DU-145, PC-3, and JCA-1 human prostate cancer cells were cultured with different concentrations of resveratrol (2. 5 x 10(-5)-10(-7) M). Cell growth, cell cycle distribution, and apoptosis were determined. Addition of 2.5 x 10(-5) M resveratrol led to a substantial decrease in growth of LNCaP and in PC-3 and DU-145 cells, but only had a modest inhibitory effect on proliferation of JCA-1 cells. Flow cytometric analysis showed resveratrol to partially disrupt G1/S transition in all three androgen-nonresponsive cell lines, but had no effect in the androgen-responsive LNCaP cells. In difference to the androgen-nonresponsive prostate cancer cells however, resveratrol causes a significant percentage of LNCaP cells to undergo apoptosis and significantly lowers both intracellular and secreted prostate-specific antigen (PSA) levels without affecting the expression of the androgen receptor (AR). These results suggest that resveratrol negatively modulates prostate cancer cell growth, by affecting mitogenesis as well as inducing apoptosis, in a prostate cell-type-specific manner. Resveratrol also regulates PSA gene expression by an AR-independent mechanism.

Adenocarcinoma↗

Double-lumen aortic arch with anomalous left pulmonary artery origin from the main pulmonary artery--bilateral persistent fifth aortic arch--a case report.

Both double-lumen aortic arch (i.e., persistent fifth arch) and anomalous origin of the left pulmonary artery from the ascending aorta (failure of the development of the sixth arch) are rare diseases. They are frequently associated with cardiovascular anomalies. However, the co-occurrence of these two diseases has not been previously reported. We report such a case in a female baby with facial anomalies similar to conotruncal anomaly face syndrome.

Abnormalities, Multiple↗

Changes in expression of the 44-kilodalton outer surface membrane antigen (p44 kD) for monitoring progression of infection and antimicrobial susceptibility of the human granulocytic ehrlichiosis (HGE) agent in HL-60 cells.

Changes in human granulocytic ehrlichiosis (HGE)-specific major outer membrane protein (p44 kD) were assayed by Western blot analysis in HL-60 cells in vitro infected by the HGE agent. Time course study demonstrated that the expression of p44 preceded the rise in cell infection as determined by the presence of intracellular morulae. To test whether the expression of p44 may be suitable for evaluating the effects of antibiotics in vitro, three recent isolates of the HGE agent were exposed to doxycycline and ampicillin during culture with HL-60 cells. Loss of infection concurrent with disappearance of the 44 kD protein was found with doxycycline treatment. In contrast, ampicillin treatment had no discernible effects on infection or 44 kD expression. There was excellent agreement between infection, as measured by morulae, and 44 kD expression (coefficient of correlation r = 0.97, p < 0.01). Following treatment with doxycycline, the 44 kD protein disappeared with an estimated t1/2 of approximately 24-30 h, which was considerably shorter than a t1/2 of >60 h calculated for loss of morulae. Measurement of p44 expression may be a more rapid and simple assay to determine antibiotic susceptibility of the HGE agent in cell culture. Furthermore, it may be used to indicate the presence of infection before morulae are apparent.

Ampicillin↗

Activation of caspase 3 in HL-60 cells exposed to hydrogen peroxide.

Recent studies have suggested that hydrogen peroxide (H2O2), a reactive compound formed endogenously in the breakdown of superoxide, may mediate the induction of apoptosis in various cell types in response to external stimuli. However, the role of H2O2 in the apoptotic pathway has not been clearly established. The purpose of this study was to determine if H2O2 treatment could induce apoptosis through the activation of caspases. Doses of H2O2 ranging from 10 microM to 100 microM, when added to HL-60 cells, resulted in the cleavage of poly(ADP-ribose) polymerase (PARP) from its native 113 Kd form to a processed 89 Kd fragment, indicative of cells undergoing apoptosis. PARP was predominantly in the fragmented form when doses of 20 microM and greater were used. A time course study of changes in PARP processing in H2O2-treated cells revealed that 10 and 50 microM H2O2 required 6 and 3 h, respectively, to specifically degrade PARP, suggesting that the H2O2-induced PARP cleavage is both time and concentration dependent. Since PARP is cleaved by CPP32 (caspase-3), we next determined if H2O2 was capable of effecting changes in CPP32 activity. The caspase activity was assayed using a colorimetric substrate, DEVD-pNa. Results of these experiments showed that H2O2 increased caspase activity at 3 h, corresponding to the time of appearance of fragmented PARP. Also, CPP32 activity and PARP processing were both significantly suppressed by caspase-3 inhibitors. Taken together, these results suggest that H2O2 mediates specific cleavage of PARP and possibly apoptosis by activating caspase 3.

Apoptosis↗

Increased serum mitogenic activity for arterial smooth muscle cells associated with relaxation and low educational level in human subjects with high but not low hostility traits: implications for atherogenesis.

Proliferation of arterial smooth muscle cells (aSMC) is a key component of atherogenesis. A sample of 225 volunteers, aged 21-65 years, was exposed to "frustration," "harassment," or "relaxation," after completing the 50-item Hostility subscale of the Minnesota Multiphasic Personality Inventory (MMPI). Whole blood was measured before and after exposure for platelet-derived growth factor (PDGF), and sera were evaluated for total and HDL cholesterol concentrations and PDGF-independent mitogenic activity (SMA). Blood pressure and pulse rate were also evaluated. Analyses of SMA (i.e., serum independent of PDGF) revealed an increase in mitogenic effect for cultured human aSMC when hostility was treated as a dichotomous modifier. Among high-hostility subjects, surprisingly, those in the relaxed group and those with a lower educational level were found to have a significant mitogen response; no significant effects were observed for the low-hostility groups. The data suggest that endogenous stresses may occur in high-hostility individuals when "relaxed," to influence proliferation of arterial smooth muscle cells, as a contribution to atherogenesis. In individuals with lower educational levels and higher hostility scores, lifestyle changes may play a role.

Adult↗

Resveratrol inhibits copper ion-induced and azo compound-initiated oxidative modification of human low density lipoprotein.

To investigate whether resveratrol, a polyphenolic compound in red wine, affects the oxidation of human low density lipoprotein (LDL), LDL purified from normolipidemic subjects was subjected to Cu(2+)-induce and azo compound-initiated oxidative modification, with and without the addition of varying concentrations of resveratrol. Modification of LDL was assessed by the formation of thiobarbituric acid reactive substances (TBARS) and changes in the relative electrophoretic mobility (REM) of LDL on agarose gels. Resveratrol (50 microM) reduced TBARS and REM of LDL during Cu(2+)-induced oxidation by 70.5% and 42.3%, respectively (p < 0.01), and prolonged the lag phase associated with the oxidative modification of LDL by copper ion or azo compound. These in vitro results suggest that resveratrol may afford protection of LDL against oxidative damage resulting from exposure to various environmental challenges, possibly by acting as a free radical scavenger.

Amidines↗

Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials.

Trans-resveratrol, a polyphenol present in red wines and various human foods, is an antioxidant also with reported chemopreventive properties. However, whether resveratrol may exert different effects in malignant cells with a common anatomical origin yet displaying different invasive characteristics is not known. Since invasiveness and metastasis are considered to be the most insidious and life-threatening aspects for all cancers, we compared the ability of resveratrol to control growth and cell cycle transition in the highly invasive MDA-MB-435 with the minimally invasive MCF-7 breast carcinoma cells. The data revealed that resveratrol exerted a greater inhibitory effect on the MDA-MB-435 cells. A diminution of percentage of cells in G1 phase and a corresponding accumulation of cells in S phase of the cell cycle was observed. We also studied the effect of resveratrol on a panel of MDA-MB-435 cells transfected with nm23-H1 and nm23-H2 genes, which have been suggested to play a role in controlling metastasis in breast cancer cells. These cells are designated as Vbeta, 1beta, 1Tbeta, 2beta, and 2Tbeta, respectively. The control Vbeta consists of MDA-MB-435 cells transfected with bacterial beta-glucuronidase. Cells labeled 1beta and 1Tbeta correspond to those carrying beta-glucuronidase and overexpressed wild-type (His118) or mutant (Tyr118, catalytically inactive) nm23-H1 genes. The 2beta and 2Tbeta refer to cells transfected with wild-type and mutant nm23-H2 genes. The responses of these cells to resveratrol were assessed by measuring proliferation, cell cycle phase distribution, and changes in expression of several genes. These studies have shown that resveratrol (25 microM, 3 days) reduced growth of all cell types by 60-80%. Overexpression of both wild-type and catalytically inactive nm23-H1 (1beta, 1Tbeta) but not nm23-H2 (2beta, 2Tbeta) reduced the proportion of cells in G1 phase, compared to the Vbeta control cells. Little changes in expression of PCNA, Rb, p53, and bcl-2 were observed in the five cell types treated with resveratrol, compared to untreated cells. Noted exceptions included reduced expression of Rb protein and increased expression of p53 in 2beta and 2Tbeta cells, and increased expression of bcl-2 in 2beta cells, treated with resveratrol. In contrast, resveratrol upregulated expression of cathepsin D by 50-100% in all cell lines except 1beta. These results suggest that the intrinsic metastatic potential of cancer cells may affect their responses to chemopreventive agents such as resveratrol.

Adenocarcinoma↗

Suppression of mitogenesis and regulation of cell cycle traverse by resveratrol in cultured smooth muscle cells.

Resveratrol (3,5,4'-trihydroxystilbene), a natural product derived from grapes, has been reported to exert a plethora of biological functions. Recent studies suggest that resveratrol could act as a cardioprotective agent by controlling the oxidation of low density lipoproteins, as well as the proliferation of endothelial cells. Since migration and proliferation of smooth muscle cells (SMCs) in the intima of susceptible vessels is also widely accepted as a requisite for atherogenesis, we investigated the effects of resveratrol on proliferation and cell cycle control of cultured smooth muscle cells. Results of these experiments are reported herein. Resveratrol reduces SMC proliferation in a dose-dependent manner, with 50-100 microM resveratrol resulting in 70-90% reduction of SMC proliferation induced by such diverse mitogens as serum, endothelin and PDGF. The anti-mitogenic effects of resveratrol are not mediated by the induction of apoptosis, but appear to relate to a G1-->S block in cell cycle traverse. These results give further support to the hypothesis that resveratrol holds promise as an anti-atherosclerotic agent.

Animals↗

The role of pulmonary inflammation in the development of pulmonary hypertension in newborn with meconium aspiration syndrome (MAS).

1. There was no clear correlation between the tracheal aspirate cytokines and the elevation of pulmonary arterial pressure in newborn piglets with MAS. The use of dexamethasone significantly suppressed tracheal aspirate cytokines but did not significantly alter pulmonary arterial pressure. Dexamethasone significantly increased the cardiac stroke volume and blood pressure. 2. Early dexamethasone therapy (< 12 hrs) for one week in infants with MAS significantly improved pulmonary ventilation and facilitated weaning from mechanical ventilation. 3. The mechanisms for the improvement in cardiopulmonary status following early dexamethasone therapy in MAS remain unclear. An overall improvement in cardiac hemodynamics, along with a significant decrease in lung inflammation may be responsible for the improvement.

Animals↗

Clinical and laboratory evolution of a culture-confirmed case of human granulocytic ehrlichiosis.

A 74-year-old man from suburban New York City, who was hospitalized because of chest pain and fever, was diagnosed as having human granulocytic ehrlichiosis on the eighth hospital day. Although leukocyte and platelet counts were normal on admission, they fell to abnormally low values then normalized prior to specific therapy against the human granulocytic ehrlichiosis agent. Intracytoplasmic inclusions suggestive of Ehrlichia were observed in up to six percent of granulocytes, and the human granulocytic ehrlichiosis bacterium was cultured in an HL 60 human promyelocytic cell line. The patient improved dramatically within 24 hours of doxycycline treatment, after failing to improve on various beta lactam antimicrobial agents. He was discharged from the hospital 14 days after admission. Because human granulocytic ehrlichiosis was not diagnosed until his eight hospital day, clinical and laboratory parameters prior to specific treatment were available. This case illustrates the clinical and laboratory evolution of the infection with human granulocytic ehrlichiosis agent in humans.

Aged↗

Antimycoplasmal activities of (S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10 -[4-(2-pyridyl)-1-piperazinyl]-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine -6-carboxylic acid (YH-6) in comparison with other antibiotics in vitro.

AIM: To determine the susceptibilities of Mycoplasma and Ureaplasma to (S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10 -[4-(2-pyridyl)-1-piperazinyl]-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine -6-carboxylic acid (YH-6) and to compare it with those referential quinolones, macrolides, and tetracyclines. METHODS: The minimum inhibitory concentration (MIC) were determined by microdilution method in vitro. RESULTS: The MIC of YH-6 for Ureaplasma urealyticum (Uu: 250 micrograms.L-1), Mycoplasma hominis (Mh: 500 micrograms.L-1), M orale (Mo: 125 micrograms.L-1) and M salivarium (Ms: 125 micrograms.L-1) were closely similar to those of macrolides (erythromycin and leucomycin) and were 2-8 folds greater than those of ofloxacin (Ofl). Uu and Mh easily induced resistance to erythromycin and tetracycline. They did not easily form resistance to quinolone (YH-6, Ofl), josamycin and tylosin. Tetracycline-resistance (Tcr) or erythromycin-resistance (EMr) strains of Uu (or Mh) had cross-resistance to erythromycin or tetracycline. However, they had no cross-resistance to quinolone, josamycin and tylosin. CONCLUSION: YH-6 was a highly active quinolone against Mycoplasma, but could hardly induce resistance to Uu. EMr- or Tcr- strains of Uu (or Mh) had no cross-resistance to YH-6.

Anti-Bacterial Agents↗

[Thermal physiological analysis of man in an Intravehicular Activity space suit].

OBJECTIVE: To analyze the thermal physiological changes of man in a Intravehicular Activity (IVA) space suit. METHOD: Combined second design was used to arrange 24 tests in 6 young male subjects wearing an IVA space suit at sea level. RESULT: The relationship between common thermal physiological measurements and air ventilating parameters (air temperature, flow rate and its relative humidity) together with metabolic state (rest or work) of man were established in mathematical models. Possible applications of these models were illustrated. Metabolic heat production which influences the relations was also discussed. CONCLUSION: Thermal physiological changes of man in the space suit were properly expressed by the mathematical models in this paper.

Adolescent↗