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Biomedical subjects

E Wang

Publications and source records attributed to E Wang.

At least 325 records · Page 18Linked to original sources
PubMed1992

Fumonisin inhibition of de novo sphingolipid biosynthesis and cytotoxicity are correlated in LLC-PK1 cells.

Fumonisins are a group of structurally related compounds produced by Fusarium moniliforme. Recently, it has been shown that fumonisins B1 and B2 are the first naturally occurring inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase) in rat primary hepatocytes (Wang et al. J. Biol. Chem. 266, 14, 486-14, 490, 1991). These enzymes are key components in the pathways for de novo sphingolipid biosynthesis and sphingolipid turnover. The results of the present study show that fumonisins B1 and B2 inhibit proliferation and are cytotoxic to LLC-PK1 cells. Concentrations of fumonisin B1 and B2 between 10 and 35 microM inhibited cell proliferation, whereas higher concentrations (greater than 35 microM) killed cells. Inhibition of cell proliferation and cell death were preceded by a lag period of at least 24 hr during which cells appeared to be functioning normally. Cells exposed to fumonisin B1 exhibited normal growth kinetics and morphology soon after fumonisin B1 was removed; thus, the effects of fumonisin B1 were reversible. The EC50 for alterations in sphingolipid biosynthesis was 10 to 15 microM. Inhibition of de novo sphingolipid biosynthesis occurred before inhibition of cell proliferation or cytotoxicity, and the dose response for the decrease in the [3H]sphingosine to [3H]sphinganine ratio at 7 hr closely paralleled the dose response for effects on proliferation and cytotoxicity at 3-5 days. In addition, the level of free sphinganine, and to a lesser extent sphingosine, increased in fumonisin-treated cells in a dose-dependent manner. During the 24-hr lag period preceding inhibition of cell proliferation, the free sphinganine content increased by 12,800% in cells exposed to 35 microM fumonisin B1. Whereas a mechanistic relationship between the inhibition of de novo sphingolipid biosynthesis and inhibition of proliferation and cell death has not been demonstrated, the results of this study support the hypothesis that inhibition of de novo sphingolipid biosynthesis is an early event in the toxicity of fumonisins to LLC-PK1 cells.

Acyltransferases↗
PubMed1992

Spermine dialdehyde, a novel ex vivo purging agent for both allogenic and autologous bone marrow transplantations.

The use of ex vivo purging agents has shown to be beneficial for both allogeneic and autologous bone marrow transplantations. We have shown previously that spermine dialdehyde (SDA), an oxidized product of spermine, when used in phosphate-buffered saline (PBS) preferentially inhibits T-cell proliferation while sparing myeloid cells. Lethally irradiated mice were rescued by reconstitution with SDA-treated allogeneic marrow and showed no sign of graft-vs-host disease (GVHD). In this paper, we show by HPLC analysis that SDA degraded rapidly in PBS but remained intact in saline. Administered in saline, SDA was more inhibitory on leukemic cell lines than normal myeloid or T-cells. Lethally irradiated mice receiving a syngeneic bone marrow leukemic cell mixture treated ex vivo with SDA in saline did not manifest leukemia. Thus, the preferential inhibitory effect of SDA and its degraded products in different buffers suggest that SDA could act as a novel purging agent for both allogeneic and autologous bone marrow transplantations.

Acrolein↗
PubMed1992

A study on the diagnosis of drowning by examination of lung chlorophyll(a) of planktons with a spectrofluorophotometer.

An investigation on the diagnosis of drowning by analysis of chlorophyll(a) (Chl.(a)) of planktons in the lung sample with a spectrofluorophotometer (SFPM) is reported. The diagnostic criteria or main points of death by drowning are suggested are according to our experimental studies. Meanwhile two cases of submersion in water were investigated and the causes of death were diagnosed correctly. It is concluded that examination of lung Chl.(a) of planktons could be used as a reliable diagnostic method in forensic practice.

Animals↗
PubMed1992

Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada.

PURPOSE: To determine the outcomes in children at high risk for death or complications from respiratory disease who are hospitalized with respiratory syncytial virus (RSV) infection. DESIGN: Retrospective chart review. SETTING: Twelve pediatric tertiary care centers. PATIENTS: All hospitalized children with an RSV infection diagnosed by a positive antigen detection test result or viral isolation during the study period from 1988 to 1991, encompassing three winter seasons. Charts from patients in the following high-risk groups were reviewed in detail: (1) congenital heart disease, (2) chronic lung disease, (3) immunodeficiency, (4) age less than 6 weeks, (5) gestational age less than 36 weeks, and (6) hypoxia (defined as oxygen saturation less than 90% or arterial oxygen pressure less than 60 mm Hg). MEASUREMENTS: The age of all children, the date of RSV identification, and the use of oxygen supplementation, intensive care, and ventilatory support. In addition, the duration of these treatments and the duration of hospitalization were noted. Left-to-right shunting and pulmonary hypertension before RSV infection were determined in those children with congenital heart disease. The nature of the chronic lung disease was noted. Death within 2 weeks of RSV identification was recorded, and the use of ribavirin, bronchodilators, and corticosteroids was determined. RESULTS: Significant year-to-year variation in the frequency of RSV infection was confirmed, with a peak during the 1989-1990 winter noted by the majority of centers (p = 0.0001). Of the 1584 patients in the study, 260 had underlying cardiac disease, 200 had chronic lung disease, 35 had compromised immune function, 378 had been premature, 373 were less than 6 weeks of age, and 338 had hypoxia. Seventeen patients died within 2 weeks (mortality rate 1%); significantly more patients with underlying cardiac disease (3.4%) or lung disease (3.5%) died. Immunocompromised patients had the longest hospital stay (median 39 days), followed by those patients with underlying cardiac or pulmonary disease (11 days); patients less than 6 weeks of age (5 days) and those with hypoxia (6 days) had the shortest hospital stays. Patients with underlying cardiac and pulmonary disease also required oxygen supplementation for a significantly longer period. CONCLUSION: The year-to-year variation in frequency of RSV infection was confirmed in this study. Morbidity and mortality rates associated with RSV infection in a high-risk population in Canada were significantly lower than previously reported.

Adolescent↗
PubMed1992

Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic-metabolizing enzymes and nitrosamine metabolism in rats.

Phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables, has been shown to inhibit chemical carcinogenesis, possibly due to its ability to block the activation or to enhance the detoxification of chemical carcinogens. The present study was conducted to elucidate the biochemical mechanisms involved by characterizing the effects of PEITC on phase I and phase II xenobiotic-metabolizing enzymes. A single dose of PEITC to F344 rats (1 mmol/kg) decreased the liver N-nitrosodimethylamine demethylase (NDMAd) activity (mainly due to P450 2E1) by 80% at 2 h and the activity of NDMAd remained decreased by 40% at 48 h after treatment. The liver pentoxyresorufin O-dealkylase (PROD) activity and P450 2B1 protein level were elevated 10- and 7-fold at 24 h after treatment respectively. The liver microsomal ethoxyresorufin O-dealkylase (EROD) (mainly due to P450 1A) and erythromycin N-demethylase (mainly due to P450 3A) activities were decreased at 2-12 h after treatment and recovered afterwards. The lung microsomal PROD and EROD activities were not significantly affected; whereas, the nasal microsomal PROD and EROD activities were decreased by 40-50%. After a treatment with PEITC, the rates of oxidative metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were decreased in liver microsomes by 40-60% at 2 h and recovered gradually; the rates in lung microsomes were markedly decreased by 60-70% at 2 h and remained at the decreased level at 24 h; and the rates in nasal mucosa microsomes were decreased gradually with the lowest activities observed at 18 h (50%) followed by a gradual recovery. Furthermore, the treatment with PEITC resulted in a maximal 5-fold increase of NAD(P)H:quinone oxidoreductase and 1.5-fold increase of glutathione S-transferase activities in the liver, but the activities of these two enzymes were not significantly affected in the lung and nasal mucosa. The sulfotransferase activity in the liver was decreased by 32-48% at 24-48 h after treatment; the nasal activity was increased by 1.8- to 2.5-fold, but the lung activity was not significantly changed. The hepatic UDP glucuronosyltransferase activity was slightly decreased at 2 h but slightly increased at 48 h after treatment, but no changes were observed for the lung and nasal activities. The study demonstrates that PEITC selectively affects xenobiotic-metabolizing enzymes in the liver, lung and nasal mucosa and it is especially effective in inhibiting the P450-dependent oxidation of NNK in the lung and of NDMA in the liver.

Animals↗
PubMed1992

Increases in serum sphingosine and sphinganine and decreases in complex sphingolipids in ponies given feed containing fumonisins, mycotoxins produced by Fusarium moniliforme.

Consumption of food contaminated with Fusarium moniliforme causes leucoencephalomalacia and hepatotoxicity in horses, pulmonary edema in pigs and liver cancer in rats, and has been correlated with esophageal cancer in humans. The causative agents are thought to be a family of compounds called fumonisins, which have recently been shown to be potent inhibitors of sphingosine (sphinganine) N-acyltransferase. Because inhibition at this step blocks the formation of complex sphingolipids while leading to accumulation of sphinganine, we hypothesized that exposure of animals to fumonisin-contaminated feed might be detected by analyses of serum sphingolipids. Within days of giving ponies feed contaminated with 15 to 44 micrograms/g fumonisin B1, there was an increase in the amount of free sphinganine (and sometimes sphingosine) and a reduction in complex sphingolipids. Free sphinganine and sphingosine decreased when ponies consumed less of the contaminated feed, and increased again when they consumed more fumonisin. When toxicosis was evident as indicated by other serum markers, complex sphingolipids as well as free sphingosine and sphinganine were elevated, probably due to loss of sphingolipids from dying cells. These findings establish that consumption of fumonisin-contaminated feed disrupts sphingolipid metabolism. Because the changes in sphinganine and sphingosine were seen before liver enzymes were noticeably elevated, they may be an early marker of exposure to fumonisins.

Animal Feed↗
PubMed1992

Evaluation of a polyepoxy compound fixed biological vascular prosthesis and an expanded polytetrafluoroethylene vascular graft.

Antithrombogenicity is one essential requirement for the successful use of small caliber vascular prostheses. In this study, a polyepoxy compound fixed, heparinized 4 mm diameter Baxter Denaflex vascular graft was evaluated against a 4 mm diameter Gore-Tex expanded polytetrafluoroethylene (ePTFE) vascular graft in the canine model. In addition to the thromboresistant characteristic conferred by heparinization, the crosslinking agent allowed the Denaflex graft to retain the original color of the native artery. Six centimeter long graft segments were implanted into the carotid arteries bilaterally in 5 dogs. The patency rate at 3 months for the Denaflex graft was 100% (five out of five) whereas in the control ePTFE graft, it was 40% (two out of five). The explanted Denaflex grafts exhibited softness and flexibility, and their luminal surfaces maintained a white color like that before implantation. To the contrary, the patent ePTFE grafts felt hard, and red thrombi covered large portions on their inner surfaces. Under microscopic observation, neointima formation was limited to regions near the anastomotic sites for both types of grafts. This experiment showed that the Denaflex vascular graft has an excellent antithrombogenic property and has a compliance similar to native arteries.

Animals↗
PubMed1992

Phorbol ester inhibits granulocyte-macrophage colony-stimulating factor binding and tyrosine phosphorylation.

Exposure of human polymorphonuclear neutrophils to phorbol 12-myristate 13-acetate (PMA) results in a 70-75% reduction in the specific binding of 125I-granulocyte-macrophage colony-stimulating factor (GM-CSF) to its receptors. The PMA-induced reduction in 125I-GM-CSF binding is due to a decrease in the number of available GM-CSF receptors, as derived from Scatchard analysis of the binding data. On the other hand, the phorbol ester 4-alpha-phorbol 12,13-didecanoate (4 alpha-PDD) fails to affect 125I-GM-CSF binding. PMA promotes phosphorylation on tyrosine residues of several proteins, as demonstrated by Western blotting analysis using antiphosphotyrosine antibodies. The molecular masses of those proteins are 41, 55, 66, 78, 85, 104, and 115 kDa. GM-CSF increases the levels of the tyrosine phosphorylation of several proteins, the majority of which have similar Mr to those found in PMA-stimulated neutrophils. This increase, on all but the 41-kDa protein, is partially prevented by treatment of the cells with PMA. The inhibition by PMA of GM-CSF binding to its receptors and its phosphorylated effects is partially prevented by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and, to a greater extent, by staurosporine. It is suggested that PMA, through the activation of protein kinase C, interrupts the excitation-response sequence initiated by GM-CSF, which includes tyrosine phosphorylation, and that the earliest altered step is the binding of GM-CSF to its receptor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Analyses of plasma for metabolic and hormonal changes in rats flown aboard COSMOS 2044.

Plasma samples from rats flown aboard COS-MOS 2044 were analyzed for the levels of key metabolites, electrolytes, enzymes, and hormones. The major differences between the flight group and the synchronous control were elevations in glucose, cholesterol, phosphate, creatinine, blood urea nitrogen, lactate dehydrogenase, and aspartate amino-transferase and decreased levels of thyroxine. Most of these differences were not mimicked by tail suspension of ground-based rats; however, both flight and suspended rats exhibited inhibited testosterone secretion. Corticosterone, immunoreactive growth hormone, and prolactin showed inconsistent differences from the various control groups, suggesting that the levels of these hormones were not due to actual or simulated microgravity.

Adrenal Glands↗
PubMed1992

Differences in glycogen, lipids, and enzymes in livers from rats flown on COSMOS 2044.

Livers from rats flown aboard COSMOS 2044 were analyzed for protein, carbohydrate (glycogen), and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. The major differences between the flight group and the synchronous control were elevations in microsomal protein, liver glycogen content, tyrosine aminotransferase, and tryptophan oxygenase and reductions in sphingolipids and the rate-limiting enzyme of heme biosynthesis, delta-aminolevulinic acid synthase. These results provide further evidence that spaceflight has pronounced and diverse effects on liver function; however, some of the results with samples from COSMOS 2044 differed notably from those from previous spaceflights. This may be due to conditions of spaceflight and/or the postflight recovery period for COSMOS 2044.

Amino Acids↗
PubMed1992

Histochemical localization of Statin--a non-proliferation-specific nuclear protein--in nuclei of normal and abnormal human thyroid tissue.

Surgical specimens of 29 human thyroid masses, both benign and malignant, were examined by means of a novel monoclonal antibody immunoreactive to statin, which is expressed only in quiescent G0 cells. The nuclei of normal thyroid follicle tissue together with nodular goitres and follicular adenomata had similar labelling indices of 96 +/- 2.67, 95 +/- 2.43 and 94 +/- 1.98 respectively. By contrast the labelling indices of papillary and undifferentiated thyroid malignancies were 82 +/- 3.05 and 15.2, respectively. These results indicate that normal thyroid tissues as well as benign thyroid tumors have similar non-proliferative activities. The differentiated papillary cancers have a smaller non-cycling compartment, the smallest being present in the most biologically aggressive undifferentiated thyroid cancer. The immunohistological evaluation of statin in the nuclei of human thyroid malignancies correlates with their biological behaviour in an inverse relationship.

Adenoma↗
PubMed1992

Bone morphogenetic protein induces bone in the squirrel monkey, but bone matrix does not.

Demineralized bone matrix (DBM) reproducibly induces extraskeletal bone formation in rodents, but its effects in dogs and primates are negative or uncertain. In previous studies on the squirrel monkey, DBM did not induce bone, although the same implants were effective in nude rats. In the present study, the DBM was augmented with recombinant human bone morphogenetic protein-2 (BMP-2). Bone was formed in 10 of 12 monkeys, as verified by histology and calcium content. However, in 4 monkeys, the induced bone mass appeared smaller than the original implant. DBM controls induced microscopic amounts of bone in 2 out of 10 monkeys. In the nude rats, all DBM controls and augmented implants induced bone. The difficulties in achieving bone induction in higher animals may be overcome, at least partially, by using a higher concentration of the inductive protein than is present in DBM.

Animals↗
PubMed1992

Fate of the autologous tri-cusp-valved pericardial conduit in the right ventricular outflow tract of growing pigs.

No perfect valve or valved conduit is currently available to reconstruct the right ventricular outflow tract (RVOT) in pediatric patients. To investigate the fate of autologous pericardial valved conduit, twenty piglets weighing 12.2 +/- 1.4 kg were divided into two groups. In 10 of them, the pericardium was immersed in 0.6% glutaraldehyde for 5 minutes (Gr PG) and then washed with normal saline. In the other 10 pigs, the pericardium was immersed in normal saline only (Gr PN) after procurement. Afterwards the autologous pericardium was tailored as designed to build a tri-cusp-valve inside the pericardial conduit with reconstruction of the sinus of Valsalva. This conduit was connected to the pulmonary trunk (PT) distally and RVOT proximally without a pump. The PT was then doubly ligated just above the annulus. The pigs survived 114 +/- 92 days in Gr PG and 82 +/- 50 days in Gr PN. The body weight increased to 42 +/- 29 kg in Gr PG and 30 +/- 9 kg in Gr PN. No cusps adhered to the conduit wall in either group. In Gr PN, the valve became retracted; in 7 of them an aneurysm developed proximal to the stenotic pulmonary valve, while only one pig in Gr PG developed an aneurysm. In Gr PG, the leaflet and conduit showed evidence of growth. In contrast, no evidence of valve growth was found in Gr PN. Calcification was evident more in Gr PG than in Gr PN either on the leaflet (9/10 vs. 5/10) or in the wall of conduit (8/10 vs. 6/10), but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Statin immunolocalization in human brain tumors. Detection of noncycling cells using a novel marker of cell quiescence.

Surgical specimens of 35 human brain tumors were examined with a novel monoclonal antibody, S-44, immunoreactive to statin, a nuclear protein specifically expressed in quiescent (noncycling) G0-phase cells. Benign tumors typically were statin positive with labeling indices (LI) between 22% and 96%: acoustic schwannomas (n = 3, mean = 29.9 +/- 19.4%); meningiomas (n = 4, mean = 59.0 +/- 15.1%); pituitary adenomas (n = 3, mean = 79.9 +/- 28.2%), and an epidermoid cyst (41.0%). By contrast, the statin LI of 18 of 24 (75%) malignant brain tumors was less than or equal to 2%: medulloblastomas (n = 7, mean = 0.3 +/- 0.2%); anaplastic astrocytomas (n = 3, mean = 1.6 +/- 2.7%); glioblastomas (n = 10, mean = 10.3 +/- 14.4%); metastatic carcinomas (n = 3, mean = 3.0 +/- 4.6); and a germinoma (0.2%). The vascular endothelium among diverse tumors typically was statin positive. All 21 tumors with a statin LI less than 10% were malignant, and all nine tumors with a statin LI greater than 40% were benign. The statin LI of benign tumors (n = 11, mean = 55.1 +/- 26.7%) was significantly higher than that of the malignant tumors (n = 24, mean = 5.2 +/- 10.5%, P less than 0.001). The absence of statin expression is a new way to determine the malignancy of human brain tumors. The statin LI may be useful to guide the prognosis and treatment of individual patients. The mechanisms that control statin expression are important in therapy seeking to shift the proliferating, cycling cells to the quiescent, G0 compartment.

Adolescent↗