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Biomedical subjects

W J Li

Publications and source records attributed to W J Li.

At least 37 records · Page 2Linked to original sources

[Prevention of fetal growth retardation by low dose aspirin].

A prospective randomized, double-blinded, controlled clinical trial was conducted in 84 pregnant women with high risk of intrauterine growth retardation (IUGR). From the 28th to 30th week of gestation, low dose aspirin 75 mg/day (study group, n = 40) or placebo (control group, n = 44) was given consecutively for 6 to 8 weeks. It was found that the mean value of systolic/diastolic ratio of umbilical artery flow velocity waveforms in the study group was significantly lower than that of the control group after drug use. The occurrences of IUGR and preeclampsia in the study group (7.5% and 10.0% respectively) were remarkably lower than those in the control group (27.3% of both). The adverse effects of low dose aspirin on both mother and fetus were not observed. These results suggest that low dose aspirin administration (75 mg/day) beginning at earlier stage of third trimester may improve the fetal placental circulation, and thus prevent IUGR and/or preeclampsia effectively.

Adolescent↗

Target therapy of ovarian carcinoma by monoclonal antibodies bearing chemical drugs entrapped in liposomes.

Monoclonal antibody COC166-9 against ovarian carcinoma was conjugated with adriamycin or cisplatinum entraped in liposomes as immunochemical liposomes MLA and MLP respectively. MLA was shown to have the highest effect than adriamycin or other groups on SKOV3 (ovarian cancer cell line) growth inhibition. MLA was also used in target therapy on nude mice bearing human ovarian carcinoma by xenograft of SKOV3 cells. The observations of tumor volumes revealed that this target therapy other than the controls presents a significantly better result which gives a hopeful clue to ovarian carcinoma treatment.

Animals↗

[Human ovarian epithelial adenocarcinoma with peritoneal metastasis and ascites established in murine models].

By means of SKOV3 subcutaneous xenografts in nude mice, both carcinoma cells and cell suspensions were administrated intraperitoneally to establish a model of metastatic ovarian carcinoma with ascites. The intraperitoneal metastasis and cancer cells in the ascitic fluid were all prove to be adenocarcinoma by microscopic and electromicroscopic examinations. The immunohistochemical and immunocytochemical stainings with monoclonal antibody COC166-9 were the same as SKOV3 cells. The median survival of these nude mice was 68.7 days. This may serve as a good experimental model for testing chemotherapy as well as immunotarget therapy. Similar results obtained by xenografts of OSC2. 40 nude mice were included in this study.

Animals↗

Changes in serum fibronectin levels at delivery in pregnant women and their fetuses with idiopathic fetal growth retardation.

We determined maternal and neonatal umbilical artery serum concentrations of fibronectin (Fn) in 15 pregnant women with idiopathic IUGR (Intrauterine growth retardation) and 17 normal pregnant women at the time of delivery, by use of a rate nephelometric procedure. The results showed that the maternal serum levels of Fn in pregnant women with idiopathic IUGR were significantly higher than those in normal pregnant women at the time of delivery (P < 0.01), but umbilical artery serum concentrations in the two groups were not significantly different (P > 0.05), suggesting that the significant increase in maternal serum levels of Fn appeared to be related to uteroplacental vascular endothelial cell lesion, formation of microthrombi and deficiency of placental perfusion.

Adult↗

Tetrodotoxin protects against acute ischemic renal failure in the rat.

Tetrodotoxin has been reported to cause prolonged systemic hypotension without resultant ischemic damage. We tested its ability to protect the kidney during 60 minutes of warm ischemia in uninephrectomized rats. Protection was observed when tetrodotoxin was given intravenously at two microgram./kg. and four microgram./kg. as assessed by serial plasma blood urea nitrogen and creatinine measurements over two weeks. Tetrodotoxin was protective when given immediately before or immediately after the ischemic period. The renal protection of tetrodotoxin was not due to its effects on renal nerves as renal denervation did not protect the kidney from the ischemic damage. The renal protective effects of four microgram. tetrodotoxin/kg. were similar to those of four mg. captopril/kg. but the combination of the two was paradoxically without effect. We tested whether tetrodotoxin and captopril chemically antagonized each other, but in the presence of tetrodotoxin, captopril was still a potent inhibitor of the conversion of angiotensin I to angiotensin II. These results indicate that tetrodotoxin could be useful in elucidating the sequence of events associated with ischemic-reperfusion renal injury and in identifying ways of preserving renal function during renal surgery.

Acute Kidney Injury↗

[Cervical ripening and drug dilatation for birth control operations].

Cervical ripening in induced labor at second trimester of pregnancy was studied in 81 cases. The method consisted of injecting diazepam gel through Foley's catheter, into the extra-amniotic space, and at the level of cervical internal os. The cervix was found to be softened, the time interval between induction and onset of labor shortened and there was no cervical laceration. A comparison between the experimental and control groups showed significant difference. The use of suppositories for cervical dilatation in 719 cases of induced abortion and 34 cases of insertion and/or removal of IUD was also studied. The results were satisfactory. The mechanism of cervical dilatation and ripening with drug had been investigated at different periods of pregnancy and in non-pregnant women as well.

Abortion, Induced↗

[Selenium content and glutathione peroxidase in erythrocytes from different populations in areas with high and low mortality of esophageal cancer].

The effects of selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity in the development of esophageal cancer was studied. The results indicated that there were no significant differences in Se level (P greater than 0.2) and GSH-Px activity (P greater than 0.1) in the normal subjects from areas with high and low esophageal cancer mortality. In an area with high esophageal cancer mortality, the Se level and GSH-Px activity of the normal, mild hyperplasia, severe dysplasia and cancer groups decreased gradually. There was a significant difference in the erythrocyte Se concentration of the normal and severe dysplasia groups (P less than 0.03). Erythrocyte Se concentration and GSH-Px activity were significantly lower in the cancer group than in the normal group (P less than 0.001; P less than 0.03). The findings suggest that low erythrocyte Se level and GSH-Px activity were the results of carcinogenesis rather than a cause.

Erythrocytes↗

[Eighty cases of alveolar hydatid disease treated with albendazole].

Alveolar hydatid disease occurs frequently in Xiji County of Ningxia. 80 cases of the disease were treated orally with albendazole from 1985 to 1988 and the short-term results proved satisfactory. The treatment consisted of two groups. Group I included 72 cases which were orally given 8-10 mg/kg.d of albendazole 2 to 3 times a day after each meal for 30 days and then stop taking the medicine for 10 days as one treatment course. The treatment continued 3-12 months comprising about 24 courses were given with the highest dosage of 412g. Group II included 8 cases who were given 15.6-20 mg/kg.d of the medicine for 14 days (one course) and every two weeks with a 10 days interval. The treatment of group II continued 3-6 months which totalled 19-24 courses with the highest dosage of 270g. All the treated patients tolerate well except that a few of them felt giddy and had diarrhoea which disappeared after the withdrawal of medicine. Through 3-5 years, follow-up observation, it was found that the gener alsymptoms of the treated patients improved and their body weight increased by 2-9.5 kg, some of them could take part in light physical labour. The jaundice index in 80% of them returned to normal. SGPT in 86.4% decreased to within normal range. The enlarged livers in half of the patients decreased by 1-6 cm. 23.7% of the patients were reexamined by B ultrasound scanning which revealed that their enlarged liver reduced in size while the liquifaction area and the shadows of calcification in the livers in 42.5% patients increased obviously.

Adolescent↗

The combined effects of shock waves and cisplatin therapy on rat prostate tumors.

The effects of focused high energy shock waves (SW) generated by the Dornier experimental XL-1 lithotripter alone or in combination with cisplatin (CDDP) on the AT-2 prostate tumor were examined. They were assessed by measuring 1) clonogenic cell survival 24 hours after treatment, 2) tumor growth delay, and 3) the number of lung metastases. The survival of clonogenic cells was reduced 38% by exposure to 2000 SW and tumor growth was delayed by 1.5 days. The limb bearing the tumor was excised in all animals when the tumor reached seven cm.3 The subsequent occurrence of lung metastases in three out of 13 unshocked animals and two out of 14 shocked animals indicated that SW did not promote the dissemination of tumor cells. At doses of one to four mg. CDDP/kg. body weight, SW exposure increased the effectiveness of the chemotherapy measured by a clonogenic assay. The fractional survival was 0.62 after 2000 SW alone, 0.23 with four mg. cisplatin/kg. alone and 0.10 after the combination treatment. At higher doses of CDDP, there was no added effect of SW over that of CDDP therapy alone. Tumor growth to one cm.3 was delayed by seven days after treatment with four mg. CDDP/kg., in comparison to untreated controls. SW exposure combined with CDDP treatment delayed the time taken for the tumor to reach one cm.3 by 13 days in comparison with untreated controls. However, the combination treatment increased animal mortality from 9% with CDDP alone to 29%. These results indicate that SW could be used focally to enhance the cell killing effects of CDDP.

Animals↗

Secretion, glycosylation, and phosphorylation of rat-specific, transformation-associated proteins in Moloney murine sarcoma virus-transformed rat cells.

Previously, we detected, by monoclonal antibody, three Moloney murine sarcoma virus (Mo-MSV)-activated intracellular transformation-associated proteins (TAP), (P66, P63, and P60) in several Mo-MSV-transformed rat cell lines (Chan et al., Biochem. Biophys. Res. Commun., 134: 1223-1230, 1986) and found the release of TAP into the extracellular medium with a change from three intracellular polypeptides to two extracellular polypeptides (P68 and P64) (Li et al., Virology, 156: 91-100, 1987). Since then, we have further analyzed TAP in terms of their secretion, glycosylation, and phosphorylation in a temperature-sensitive Mo-MSV-transformed normal rat kidney (NRK) cell line, the 6M2 line, and found these results. Extracellular TAP were detected by immunoblotting and immunoprecipitation techniques as two polypeptides (P68 and P64). The secretion of TAP was rapid, with a 50% secretion rate of 78 min. Both intracellular (except for P63) and extracellular TAP were glycosylated. As a result of inhibition of glycosylation by the antibiotic tunicamycin, a fourth intracellular TAP (P58) and a third extracellular TAP (P60) were found. The new results suggest that the intracellular TAP were probably changed from four polypeptides (P66, P63, P60, and P58) to three (P66, P63, and P60) during the glycosylation process. Likewise, the three extracellular TAP were changed to two (P68 and P64) as a result of further glycosylation and subsequent secretion into the extracellular medium. Inhibition of glycosylation by tunicamycin (0.5 microgram/ml) reduced the TAP secretion rate by about 39%. Extracellular TAP (P68 and P64) as well as P85gag-mos and P58gag were found to be phosphoproteins.

Animals↗

Characterization of bcr gene products in hematopoietic cells.

The bcr gene plays a critical role in the pathogenesis of two human leukemias associated with the Philadelphia chromosome: chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). In both instances a chimeric gene, formed between bcr and the abl protooncogene, results in expression of fused bcr-abl proteins with tyrosine kinase activity. There is controversy regarding the normal gene products of bcr. We investigated this problem by several techniques and found proteins of 190/185, 155, 135, 125, 108, 83 and 47 kDa in several human cell lines by immunoprecipitation with two distinct site-directed anti-bcr antibodies termed anti-bcr(738-753) and anti-bcr(898-911). The 190/185, 155, 125 and 108 kDa proteins were consistently detected by anti-bcr(898-911) antibodies by immunoblotting. Antibodies pre-reacted with excess bcr peptide did not detect these proteins. These proteins were labeled with [32P]orthophosphate in vivo and in vitro by [gamma 32P]ATP in immune complex kinase assays performed with anti-bcr antibodies indicating that these proteins are phosphorproteins. Following labeling in kinase assays, phosphoamino acid analyses detected both phosphoserine and phosphothreonine. In structural studies using one dimensional peptide maps derived by partial V8 protease treatment, the 185, 155, 135, 125 and 108 kDa proteins shared several peptide fragments but contained unique fragments as well. Similarly 2-dimensional maps of proteins labeled in the kinase assay exhaustively digested with trypsin, revealed homology between the 155, 135, 125, 108, and 83 kDa proteins. bcr proteins sedimented in glycerol gradients as putative complexes detected in the cytoplasm of the cell. A 47 kDa protein as well as the recently identified Ph-P53 protein appeared to be associated with bcr proteins based on their co-sedimentation in glycerol gradients and co-immunoprecipitation with several different anti-bcr antibodies. None of the proteins exhibited a precursor-product relationship in pulse-chase experiments conducted with [35S]methionine. We conclude that human cells express several different bcr gene products ranging in size from 190 to 83 kDa, and that these proteins can form specific intracellular cytoplasmic complexes with other cellular proteins.

Adenosine Triphosphate↗

Differential effects of tumor promoters on P210bcr-abl expression.

It is a widely held theory that the bcr-abl hybrid gene plays an active role in chronic myelogenous leukemia (CML). The bcr-abl gene product (P210bcr-abl) is a structurally altered and enzymatically activated form of the normal c-abl gene product. P210bcr-abl is expressed in two cell lines derived from CML patients in blast crisis: K562 and EM2. Activation of protein kinase C by the strong tumor promoter TPA induced dramatic changes in K562 cells. We have shown that exposure of K562 cells to low concentrations (10 nM) of TPA stopped cell division and sharply reduced the expression of P210bcr-abl. In contrast, similar treatment of EM2 cells resulted in a slightly increased proliferation rate and stimulation of P210bcr-abl expression. A second tumor promoter, mezerein, also dramatically reduced P210 levels in K562 cells and elevated them in EM2 cells. These observations establish that expression of the bcr-abl gene can be either increased or decreased, depending on the cell type, and that these effects correlate with the proliferative state of the cell. These results are consistent with the hypothesis that P210bcr-abl plays an important role in the maintenance of CML.

Antineoplastic Agents, Phytogenic↗

A novel 53 kDa protein complexed with P210bcr-abl in human chronic myelogenous leukemia cells.

Leukemic cells from patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) contain a 210 kDa protein (P210bcr-abl) with a protein tyrosine kinase activity that is a product of fused bcr and abl genes. We have prepared two monoclonal anti-peptide antibodies, one from each gene product, and have affinity purified each. Incubation of anti-abl (c-abl 51-64) immunoprecipitates of K562 cells with [gamma-32P]ATP in protein kinase assays resulted in the labeling of P210bcr-abl and a 53 kDa (ph-P53) protein. Increasing concentrations of antibody detected similar ratios of P210bcr-abl: ph-P53, suggesting the presence of a complex between the proteins. Several different anti-abl and anti-bcr antibodies detected the ph-P53/P210 complex. Sodium dodecyl sulfate (SDS) treatment without 2-mercaptoethanol eluted P210bcr-abl and ph-P53 from the monoclonal antibody in the form of complexes which migrated on 6% SDS-polyacrylamide gels and had apparent molecular weights of 275,000 and more than 500,000. Both complexes yielded ph-P53 and P210bcr-abl upon treatment with SDS-mercaptoethanol. Studies involving glycerol gradient centrifugation also detected complexes of P210bcr-abl and ph-P53. Our results indicate that ph-P53 is not a degraded product of P210bcr-abl, does not share antigenic determinants with P210bcr-abl since it is not recognized by anti-abl and bcr antibodies in immunoblots, is not the phosphorylated heavy chain of immunoglobulin G, and is different from p53 (the nonviral T protein) complexed to the large T antigen of simian virus 40. Previous studies (Maxwell et al., 1987) have shown that ph-P53 has a different peptide map than P210bcr-abl. Therefore, we conclude that ph-P53 is a distinct cellular protein complexed to P210bcr-abl in K562 cells.

Cell Fractionation↗

Rat transformation-associated proteins (TAP) induced by Moloney murine sarcoma virus interact with specific receptors on normal rat kidney cells.

In this report, data are presented to show that transformation-associated proteins (TAP) secreted from the transformed 6M2 cells have mitogenic activities in the stimulation of DNA synthesis and proliferation of normal rat kidney (NRK-2) cells and of nonpermissively grown 6M2 cells. TAP also bound specifically to NRK-2 cells with a binding dissociation constant (Kd) of 1.4 pM. Approximately 2 X 10(5) binding sites per cell were found. Therefore, TAP may represent a set of virally-induced growth stimulatory factors.

Animals↗