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Biomedical subjects

L H Wei

Publications and source records attributed to L H Wei.

12 recordsLinked to original sources
PubMed2000

Induction of arginase II in human Caco-2 tumor cells by cyclic AMP.

The objective of this study was to elucidate the mechanism by which cyclic AMP increases arginase activity in cultured human Caco-2 tumor cells. Caco-2 cells were incubated for 24 h in the presence of 8-bromo cyclic AMP or forskolin, and the cells were harvested, lysed, and assayed for total arginase activity. Both test agents increased arginase activity by twofold, and this was attributed to the induction of the arginase II isoform. Both arginase II mRNA and protein showed increased expression in response to 8-bromo cyclic AMP and forskolin, and these effects were inhibited by H-89 (protein kinase A inhibitor), enhanced by okadaic acid (phosphatase inhibitor), and enhanced by 1-methyl-3-isobutylxanthine (cyclic nucleotide phosphodiesterase inhibitor). Cyclic GMP did not appear to be involved in arginase II induction. These observations indicate that cyclic AMP stimulates arginase II gene expression by mechanisms involving activation of protein kinase A and consequent activation of appropriate transcription factors.

1-Methyl-3-isobutylxanthine↗
PubMed2000

IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells.

The objectives of this study were to determine whether rat aortic smooth muscle cells (RASMC) express arginase and to elucidate the possible mechanisms involved in the regulation of arginase expression. The results show that RASMC contain basal arginase I (AI) activity, which is significantly enhanced by stimulating the cells with either interleukin (IL)-4 or IL-13, but arginase II (AII) expression was not detected under any condition studied here. We further investigated the signal transduction pathways responsible for AI induction. AI mRNA and protein levels were enhanced by addition of forskolin (1 microM) and inhibited by H-89 (30 microM), suggesting positive regulation of AI by a protein kinase A pathway. Genistein (10 microgramg/ml) and sodium orthovanadate (Na(3)VO(4); 10 microM) were used to investigate the role of tyrosine phosphorylation in the control of AI expression. Genistein inhibited, whereas Na(3)VO(4) enhanced the induction of AI by IL-4 or IL-13. Along with immunoprecipitation and immunoblot analyses, these data implicate the JAK/STAT6 pathway in AI regulation. Dexamethasone (Dex) and interferon (IFN)-gamma were investigated for their effects on AI induction. Dex (1 microM) and IFN-gamma (100 U/ml) alone had no effect on basal AI expression in RASMC, but both reduced AI induction by IL-4 and IL-13. In combination, Dex and IFN-gamma abolished AI induction by IL-4 and IL-13. Finally, both IL-4 and IL-13 significantly increased RASMC DNA synthesis as monitored by [(3)H]thymidine incorporation, demonstrating that upregulation of AI is correlated with an increase in cell proliferation. Blockade of AI induction by IFN-gamma, H-89, or genistein also blocked the increase in cell proliferation. These observations are consistent with the possibility that upregulation of AI might play an important role in the pathophysiology of vascular disorders characterized by excessive smooth muscle growth.

Animals↗
PubMed1999

The possible use of colour flow Doppler in planning treatment in early invasive carcinoma of the cervix.

OBJECTIVE: To investigate the pathological significance of intra-tumoural blood flow signals detected by colour Doppler ultrasound and their association with angiogenesis in cervical carcinoma. DESIGN: A prospective cross-sectional study. SETTING: University hospital. POPULATION: One hundred and four women with Stage IB-IIA cervical carcinoma. METHODS: All women underwent radical hysterectomy and pelvic lymph node dissection. Transvaginal colour Doppler ultrasound was performed before surgery to search for arterial blood flow signals within the tumours. Tumours with a measurable intra-tumoural resistance index were defined as tumour with detectable blood flow and the others as tumour with undetectable blood flow. The microvessel density of the excised tumour was assessed immunohistochemically. The women's clinical and pathologic data were recorded. RESULTS: There were 60 tumours (58%) exhibiting detectable intra-tumoural blood flow signals. Tumours with detectable blood flow were larger, had deeper cervical stromal invasion, a higher incidence of parametrial invasion and pelvic lymph node metastases, and a higher microvessel density, when compared with those without detectable blood flow. Cervical cancers with deep cervical stromal invasion, parametrial invasion, and pelvic lymph node metastasis had higher microvessel density than those with superficial stromal invasion, no parametrial invasion, or no lymph node metastasis. Microvessel density correlated well with lymph node metastases and parametrial invasion by multiple regression analysis, while intra-tumoural blood signals only showed correlation with parametrial invasion. In the prediction of pelvic lymph node metastases and parametrial invasion, colour flow Doppler had a sensitivity of 0.80 and specificity of 0.48 in predicting lymph node metastases, and sensitivity of 0.91 and specificity of 0.57 in predicting parametrial invasion. CONCLUSIONS: The characteristics of blood flow signals in cervical carcinoma detected by colour Doppler ultrasound are associated with tumour angiogenesis and could reflect the likelihood of parametrial invasion and lymph node metastases in cervical carcinoma. The intra-tumoural blood flow signals might be used as a screening test in predicting parametrial invasion and pelvic lymph node metastases. These findings may be helpful in planning treatment for women with Stage I and II cervical carcinoma.

Adenocarcinoma↗
PubMed1998

Certain S-substituted isothioureas not only inhibit NO synthase catalytic activity but also decrease translation and stability of inducible NO synthase protein.

In an attempt to identify potent inhibitors of inducible (type II) NO synthase (iNOS) for use in cell culture systems, we found that two S-substituted isothioureas were very potent in cell culture but one such compound also interfered with the induction of NO synthase. S-Ethylisothiourea (EITU) and S-aminoethylisothiourea (AEITU) were found to be much more potent than NG-methylarginine, NG-nitroarginine methy lester, or aminoguanidine as inhibitors of NO production by cultured RAW 264.7 cell macrophages activated by lipopolysaccharide (LPS). The approximate EC50 values as inhibitors of NO production, assessed by 24-h accumulation in cell culture media, were 10 microM (EITU), 30 microM (AEITU), 300 microM (NG-methylarginine), and 1000 microM (aminoguanidine). EITU was found to inhibit NO production by activated macrophages without interfering with the induction of iNOS. More specifically, EITU failed to influence transcription of iNOS mRNA (Northern blot analysis), translation of iNOS protein (pulse experiments), or degradation of translated iNOS protein (pulse-chase experiments). In contrast, however, AEITU interfered markedly with the induction of iNOS by mechanisms attributed to inhibition of translation of iNOS mRNA into functional protein as well as acceleration of degradation of already translated iNOS protein. These observations indicate that AEITU should not be used in cell culture experiments where the intent is solely to assess the consequences of inhibition of iNOS catalytic activity.

Animals↗
PubMed1998

NG-hydroxy-L-arginine and nitric oxide inhibit Caco-2 tumor cell proliferation by distinct mechanisms.

The objective of this study was to elucidate the role and mechanism of nitric oxide (NO) synthase (NOS) in modulating the growth of the Caco-2 human colon carcinoma cell line. The two novel observations reported here are, first, that NG-hydroxy-L-arginine (NOHA) inhibits Caco-2 tumor cell proliferation, likely by inhibiting arginase activity, and, second, that NO causes cytostasis by mechanisms that might involve inhibition of ornithine decarboxylase (ODC) activity. Both arginase and ODC are enzymes involved in the conversion of arginine to polyamines required for cell proliferation. Cell growth was monitored by cell count, cell protein analysis, and DNA synthesis. NOHA (1-30 microM) and NO in the form of DETA/NO (1-30 microM) inhibited cell proliferation by 30-85%. The cytostatic effect of NOHA was prevented by addition of excess ornithine, putrescine, spermidine, or spermine to cell cultures, whereas the cytostatic effect of NO (DETA/NO) and alpha-difluoromethylornithine (ODC inhibitor) was unaffected by ornithine but was prevented by putrescine, spermidine, or spermine. The cytostatic effect of NOHA appeared to be independent of its conversion to NO, and the effect of NO appeared to be independent of cGMP. NOHA inhibited urea production by Caco-2 cells and inhibited arginase catalytic activity (85% at 3 microM), whereas NO (DEA/NO and SNAP) inhibited ODC activity (>/=60% at 30 microM) without affecting arginase activity. Coculture of Caco-2 cells with lipopolysaccharide/cytokine-activated rat aortic endothelial cells markedly slowed Caco-2 cell proliferation, and this was blocked by NOS inhibitors. These observations that NOHA and NO may inhibit sequential steps in the arginine-polyamine pathway suggest a novel biological role for NOS in the inhibition of cell proliferation of certain tumor cells and possibly other cell types.

Animals↗
PubMed1996

Cystatin C. Icelandic-like mutation in an animal model of cerebrovascular beta-amyloidosis.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) occurs as a sporadic disorder in aged humans, as a frequent component of Alzheimer's disease, or in hereditary cerebral hemorrhage with amyloidosis (HCHWA). The primary histological locus of cerebral amyloid deposition varies in aged humans and in different species of nonhuman primates. In aged rhesus monkeys, amyloid deposition occurs most frequently in senile plaques, whereas in aged squirrel monkeys CAA is more common. We hypothesized that the preponderance of CAA in squirrel monkeys is related to a species-specific amino acid change in cystatin C, a cysteine protease inhibitor, similar to the Leu68Gln substitution found in the amyloid protein of Icelandic patients with HCHWA-I, also termed hereditary cystatin C amyloid angiopathy. METHODS: We performed immunohistochemical analyses of brain sections of aged squirrel and rhesus monkeys with anti-amyloid-beta and anti-cystatin C antibodies and sequenced the cystatin C cDNA of these monkeys. RESULTS: Cerebral amyloid in aged squirrel and rhesus monkeys, previously shown to be immunoreactive with anti-amyloid-beta anti-bodies, reacts also with antibodies to cystatin C. While the predicted amino acid sequence in rhesus monkeys differs from the human sequence by four residues, that of the squirrel monkeys has seven additional amino acid substitutions, one of which is Leu68Met. CONCLUSIONS: The presence of a mutation in squirrel monkeys similar to the one found in HCHWA-I suggests that alterations in cystatin C may influence the likelihood that amyloid will be deposited in the walls of cerebral blood vessels. These observations support the utilization of the monkeys as models to study CAA.

Amino Acid Sequence↗
PubMed1994

[Analysis of complications associated with catheter intraperitoneal chemotherapy of ovarian carcinoma].

115 patients suffering from ovarian carcinoma were admitted from May 1976 through August 1991, and were treated with intra-peritoneal chemotherapy. A total of 191 catheters which with 2mm in diameter and 50 cm in length were inserted with 608 courses of chemotherapy. 29 plastic catheters used by 29 patients were kept for 18.4 days averagely, while 162 silica catheters used by 86 patients were kept 109 days in average. The duration of keeping silica catheters was significantly longer than plastic catheters (P < 0.01). Complications were found in 29 patients, 25.2% of the total: 5 cases of infection (4.3%), 2 of partial intestinal obstruction (1.7%), 4 of painful sensation (3.5%), 12 with inflow obstruction (10.4%) and 6 with falling off of the catheters (5.2%). Complications between the two groups were compared. There was no statistical significance (P < 0.05). When catheter retainment times of the two groups were compared, significant differences were found between plastic and silica catheters (P < 0.001). Our results indicate that both kinds of catheters may be used in intraperitoneal chemotherapy of ovarian cancer patients, and the silica ones seem better.

Abdominal Pain↗
PubMed1994

[Gynecologic operations on patients with valvular heart disease or after cardiac valvular replacement surgery].

For patients with valvular heart disease or after cardiac valvular replacement surgery, the indication of gynecologic operations are remains undefine. We investigated 23 patients who undergoing gynecologic operations with valvular heart disease or after cardiac valvular replacement surgery. The current studies suggest that (1) general gynecologic operations can be performed on patients with valvular heart disease or mild cardiac dysfunction (New York Heart Association, NYHA, classification I-II) under carefully cardiovascular monitoring. (2) gynecologic operations should be done early on patients with giant gynecologic tumor which suggest malignancy and mild cardiac dysfunction (NYHA I-III). (3) on patients with repeated vaginal bleeding and anemia which induced heart failure, gynecologic operations should be performed immediately after cardiac function recovery. (4) on patients who have had mechanical cardiac valvular replacement, anticoagulant therapy should be stopped at 48 hours before gynecologic operations, and resumed at 48 hours after operations to avoid thromboembolism.

Adenoma↗
PubMed1989

[The isolation and identification of PAF inhibitors from Piper wallichii (Miq.) Hand-Mazz and P. hancei Maxim].

Platelet activating factor (PAF) is a highly potent endogenous phospholipid mediator, involved in various inflammatory and cardiovascular disorders. As part of a research program dealing with PAF inhibitors isolated from Piper plant species, we have isolated kadsurenone (I), denudatin B (II), and N-isobutyl-deca-trans-2-trans-4-dienamide (III) from Piped wallichii (Miq.) Hand-Mazz. and P. hancei Maxim. In a continuing search for potential PAF inhibitor from plants, using PAF induced platelet aggregation as a guide, a new neolignan named hancinone D (IV) was isolated from P. hancei maxim. By X-ray analysis it was identified as a racemate. The X-ray analysis led to a revision of the previously made structure assignment of hancinone C. Another new neolignan named wallichinine (V), which was identified as an analogue of (IV), along with the known compounds hancinone C (VI), galgravin (VII), dihydropiperlonguminine (VIII) and crotepoxide (IX) were isolated from P. wallichii (Miq.) Hand-Mazz. The structure determination was based upon spectroscopic analysis. All of the compounds were for the first time obtained from both plants. In the test of platelet aggregation caused by PAF, I, II, V, VI, VII showed inhibitory activity, whereas III, IV, VII, IX showed no activity.

Anisoles↗
PubMed1989

[Experimental heterotransplantation of human ovarian tumors in nude mice].

Human ovarian tumors tissue taken from four surgical specimen were transplanted subcutaneously into female nude mice. The primary tissue transplantations were all successful, and the mean survival time was 15 weeks. One of the four ovarian carcinomas has been successfully transplanted to the 9th passage. Time needed for each passage was 4-6 weeks. The transplanted tumors examined histologically, cytologically and by electro-microscope, resembled the original ovarian cancer. Immunohistochemical tests were positive. Chromosome number was subdiploid and aneuploid.

Animals↗