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Biomedical subjects

S Fan

Publications and source records attributed to S Fan.

At least 109 records · Page 6Linked to original sources
PubMed1997

[Bacterial vaginosis in pregnant women].

OBJECTIVES: To determine the prevalence of bacterial vaginosis (BV) in pregnant women and to assess the association between BV and adverse pregnancy outcome. METHODS: Bacterial vaginosis was screened in 380 healthy pregnant women during different gestational weeks by clinical features and Grams stained vaginal smears. The pregnancy outcome of these gravidae was followed up. RESULTS: The prevalence of BV in pregnant women was 6.8% (26/380). The incidence of puerperal infection, neonatal infection, and jaundice of newborn were higher in women with BV than those without BV (14.3%, 9.5%, and 23.8% v.s. 2.2%, 1.3%, and 5.4%, respectively P < 0.05, P < 0.05, P < 0.005). CONCLUSION: Pregnant women with BV are associated with maternal infection, neonatal infection, and jaundice of newborn. It is necessary to treat BV during pregnancy.

Adult↗
PubMed1997

Inactivation of p53 increases the cytotoxicity of camptothecin in human colon HCT116 and breast MCF-7 cancer cells.

Camptothecin (CPT) derivatives are topoisomerase I (top1) inhibitors recently introduced as clinical agents. To explore the role of p53 in CPT-induced cytotoxicity, we examined CPT effects in two isogenic pairs of human cancer cell lines, MCF-7 breast carcinoma and HCT116 colon carcinoma cells, in which p53 function had been disrupted by transfection with the human papillomavirus type-16 E6 gene. Clonogenic survival assays showed that both MCF-7/E6 and HCT116/E6 cells were more sensitive to CPT. No differences in top1 protein levels and activity analyzed by a novel in vitro oligonucleotide assay were observed in the E6 transfectants. Also, CPT showed comparable top1 cleavable complex formation in vivo, as determined by DNA single-strand breaks and DNA protein cross-links. These results suggest that p53 can protect against CPT-induced cytotoxicity and that this protection is mediated downstream of CPT-induced DNA damage. Flow cytometry analyses showed that CPT can induce G1 arrest in cells with normal p53. This G1 arrest was markedly reduced in the p53-deficient cells. These results demonstrate a critical role of p53 as a G1 checkpoint regulator after CPT-induced DNA damage and suggest a rationale for the selectivity of CPT toward tumors with p53 mutations.

Adenocarcinoma↗
PubMed1996

UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53.

BACKGROUND: Arrest of the cell cycle in G2 phase following DNA damage helps protect cell viability by allowing time for DNA repair before entry into mitosis (M phase). Abrogation of G2 arrest sensitizes cells to the effects of DNA-damaging agents. UCN-01 (7-hydroxystaurosporine), a protein kinase C inhibitor that may block G2 checkpoint regulation, has been reported to enhance the cytotoxicity of mitomycin C, a known DNA-damaging agent. PURPOSE: We studied the effect of UCN-01 on G2 checkpoint control in human lymphoma CA46 cells, whose sensitivity to various DNA-damaging agents and G2 response to DNA damage have been characterized. We also assessed the ability of UCN-01 to enhance the cytotoxicity of gamma irradiation in CA46 cells and human colon carcinoma HT-29 cells, both of which are mutant for p53 function. The influence of p53 function on UCN-01-mediated abrogation of the G2 checkpoint and enhancement of DNA-damaging agent cytotoxicity was studied in transfected human breast carcinoma MCF-7 cells that either expressed or did not express the human papillomavirus type-16 E6 protein. MCF-7 cells have normal p53 function, and the E6 protein binds p53 protein and promotes its destruction. METHODS: The effect of UCN-01 on cell cycle arrest induced by gamma irradiation was studied in CA46 cells and in transfected MCF-7 cells by use of flow cytometry. A histone H1 phosphorylation assay was employed to measure cyclin B1/Cdc2 kinase activity in extracts derived from irradiated and nonirradiated CA46 cells that had been either treated or not treated with UCN-01; the phosphorylation status of Cdc2 kinase protein in the same extracts was determined by use of western blotting. The effect of UCN-01 on the cytotoxicity of gamma irradiation in CA46 and HT-29 cells was determined by use of MTT (thiazolyl blue) and clonogenic (colony-forming) assays, respectively; a clonogenic assay was also used to measure the effect of UCN-01 on the cytotoxicity of cisplatin in transfected and nontransfected MCF-7 cells. RESULTS: G2 arrest induced in CA46 cells by gamma irradiation was minibited by treatment with UCN-01 in a dose-dependent manner; arrest in G2 was completely abrogated by exposure to 300 nM UCN-01. Biochemical markers indicative of the G2/M transition, including the activation of cyclin B1/Cdc2 kinase and the suppression of Cdc2 threonine-14 and tyrosine-15 phosphorylation, were detected in irradiated cells treated with UCN-01. UCN-01 enhanced the cytotoxicity of gamma irradiation in CA46 and HT-29 cells. MCF-7 cells with functional p53 protein were more resistant to G2 checkpoint abrogation by UCN-01 than MCF-7 cells with disrupted p53 function. UCN-01 markedly enhanced the cell-killing activity of cisplatin in MCF-7 cells defective for p53 function. CONCLUSIONS AND IMPLICATIONS: UCN-01 is a potent abrogator of G2 checkpoint control in cancer cells with disrupted p53 function. UCN-01 might be capable of enhancing the effectiveness of DNA-damaging agents in the treatment of tumors with cells lacking normal p53 function.

Alkaloids↗
PubMed1996

Effects of depletion of intracellular tetrahydrobiopterin in murine erythroleukemia cells.

The biosynthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH4) in murine erythroleukemia (MEL) cells is almost completely inhibited by 10 mM, 2,4-diamino-6-hydroxypyrimidine (DAHP), which targets GTP cyclohydrolase. The inhibition results in dephosphorylation of the retinoblastoma gene product, prolongation of the G1-phase in the cell cycle, and subsequent commitment to terminal differentiation of MEL cells. Reversal of the processes by repletion of cellular BH4 with biopterin-related compounds including BH4, 7,8-dihydrobiopterin (7,8-BH2), sepiapterin, and 7,8-dihydroneopterin has generated complicated results. Low micromolar exogenous pterin compounds had little or no effect. At 300 microM or higher, the synthesis of hemoglobin by DAHP-induced MEL cells is significantly inhibited by 7,8-dihydrobiopterin and sepiapterin. However, further cell cycle analysis shows that the inhibition of cell differentiation by 7,8-BH2 and sepiapterin may not be due to the reversal of cell proliferation. Inhibition of BH4 biosynthesis in MEL cells by inhibitors of sepiapterin reductase has also been studied. None of the inhibitors that were tested, including N-chloroacetyl-dopamine and N-acetylserotonin, which are specific for sepiapterin reductase, can block MEL cells in G1-phase or induce the cells to commit to terminal differentiation. Furthermore, inhibitors of sepiapterin reductase are found to reduce or to abolish hemoglobin synthesis in differentiating MEL cells induced by hexamethylene bisacetamide. The mechanism for this is not clear. Not all of the effects caused by the depletion of BH4 synthesis can be rescued by repletion of BH4. These results suggest that BH4 may not regulate proliferation or differentiation of MEL cells as previously thought. Its function in MEL cells is still not clear.

Acetamides↗
PubMed1996

DNA damage checkpoints: implications for cancer therapy.

DNA damage evokes a complex array of cellular responses, including cycle arrest in late G1 and/or G2 phases, and delayed progression through S phase. Arrest at these points in the cell cycle is governed, in large part, by a series of control systems, commonly termed "checkpoints". Activation of these checkpoints tends to protect cells from DNA damage by providing cells additional time to complete DNA repair. We discuss the impact of these DNA damage checkpoints on the chemosensitivity of human cancer cells. We focus on some of the complexities of the p53-dependent G1 checkpoint and review some recently discovered vulnerabilities in p53 disrupted cells that might be pharmacologically exploited for cancer treatment.

Animals↗
PubMed1996

Abrogation of p53 function affects gadd gene responses to DNA base-damaging agents and starvation.

The tumor suppressor p53 is required for induction of its downstream effector genes such as GADD45 and CIP1/WAF1 by ionizing radiation (IR). This response is probably mediated through defined p53 binding sites located in the promoter of CIP1/WAF1 and in the third intron of GADD45. In contrast, the gadd gene stress response to base-damaging agents, such as methylmethane sulfonate (MMS) or UV radiation, or medium depletion (starvation) occurs in all mammalian cells examined to date regardless of p53 status for both GADD45 and also GADD153, which is not IR-responsive in many lines with functional p53. These agents strongly induce the p53 protein and raise the possibility that, although p53 is not required for the typical "gadd" response to these agents, p53 may contribute to these non-IR stress responses. This possibility was confirmed by the finding that disruption of p53 function by transfection with dominant-negative vectors expressing HPV E6, mutant p53, or SV40 T Ag reduced the induction of GADD45 and GADD153 as measured by increases in mRNA and protein levels in human lines with wild-type p53. Similarly, induction of these genes by MMS or UV radiation was consistently stronger in the parental mouse embryo fibroblasts compared to cells derived from mice where both p53 alleles had been deleted. Similar qualitative responses were also seen for CIP1/WAF1. In agreement with reduced induction of p53-regulated genes, the G1 checkpoint activated by MMS or UV radiation was markedly abrogated in p53-wt human MCF-7 breast carcinoma cells by E6 expression. Interestingly, induction of reporter constructs driven by the GADD45 or GADD153 promoters was substantially reduced in human cells transfected with mutant p53 or E6 expression vectors or in cells lacking p53 following treatment with MMS, UV radiation, or starvation. Because neither promoter is inducible by IR, and neither contains a strong p53 binding site, these results indicate that p53 has a synergistic or cooperative role in these non-IR stress responses for both GADD45 and GADD153, and that this role is not mediated through identifiable p53-binding sites.

Animals↗
PubMed1996

Adenovirus E4 open reading frame 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter.

Here we show that the adenovirus early region 4 (E4) open reading frame 4 (ORF4) protein autoregulates its own transcription by inhibiting adenovirus E1A-induced activation of E4 transcription both in transient transfection experiments and during lytic virus growth. The inhibitory activity of E4-ORF4 was selective for E1A-CR3-dependent transactivation and had no effect on CR1 transactivation. The inhibitory activity of E4-ORF4 was relieved by okadaic acid treatment, which inhibits the cellular protein phosphatase 2A (PP2A), suggesting that E4-ORF4 controls the phosphorylated status of transcription factors important for E4 promoter activity. This conclusion agrees with previous demonstrations that E4-ORF4 associates with PP2A and causes a partial dephosphorylation of certain transcription factors, including E1A (U. Müller, T. Kleinberger, and T. Shenk, J. Virol. 66:5869-5878, 1992; T. Kleinberger and T. Shenk, J. Virol. 67:7556-7560, 1993). However, our results indicate that dephosphorylation of E1A itself might not be the primary target for E4-ORF4. Instead, the E4-ORF4-PP2A complex appears to work by dephosphorylation of multiple cellular transcription factors that are involved in E1A transactivation of the E4 promoter.

Adenoviridae↗
PubMed1996

Treatment of advanced gastric cancer with a modified regimen of etoposide/leucovorin/5-fluorouracil.

The efficacy and toxicity of a combination of etoposide 100 mg/m2/day iv on day 2-4, leucovorin 300 mg/m2/day iv, and 5-FU 500 mg/m2 day iv on day 1-5 every 4 weeks were assessed in 21 patients with advanced gastric cancer with measurable or evaluable diseases. Eight patients had an objective response, including 3 in CR. The overall response rate was 38.1% (95% CI 33.4-42.8%). Five of 8 patients who exhibited locally advanced and unresectable diseases had an objective response (2 CR, 3 PR). The response rate in patients with metastatic disease was 23.0% (95% CI 14.4-31.6%). The median progression-free interval and overall survival time were 7 and 10 months, respectively. The most frequent side effect was alopecia (Gr I/II 71.4%). No treatment-related death occurred. Modified ELF is a relatively effective and tolerable combination regimen for advanced gastric cancer and can be safely administered to elderly patients and patients with systemic diseases.

Adenocarcinoma↗
PubMed1996

High-dose cytarabine and mitoxantrone as salvage therapy for refractory non-Hodgkin's lymphoma.

BACKGROUND: High-dose cytarabine (ara-C) alone or in combination with mitoxantrone each has shown to be active in therapeutic trials of refractory non-Hodgkin's lymphoma (NHL). In this study, we administered these two drugs to 14 patients with advanced and refractory NHL. METHODS: Ara-C was administered at a dosage of 3 gm/sqm for 2-hour intravenous infusion every 12 hours from day 1 to day 4 (8 doses), and mitoxantrone was given at a dosage of 6 mg/sqm/day for 1-hour intravenous infusion from day 1 to day 5. The clinical efficacy and toxicity were assessed by WH0 criteria. RESULTS: Four patients (28%) attained complete remission (CR) and 2 had partial remission (PR). Of the 4 CR patients, the remission lasted 5 months in one patient and 4 months in another. The remaining 2 patients had CR of only 1.3 months. Myelosup-pression with subsequent infection was the major toxicity of this regimen. Severe neutropenia (<1,000/uL) lasted for an average of 20 days, and thrombocytopenia (<50,000/uL) 24 days. Nonmyeloid toxicities included 100% alopecia, 93% stomatitis, 43% hepatotoxicity, 36% dermatitis, 28% CNS toxicity and 7% chemical conjunctivitis. CONCLUSIONS: A proportion of refractory NHL patients will respond to high-dose ara-C + mitoxantrone, despite that severe myelosuppression is frequently encountered.

Adult↗
PubMed1996

Selective IgA deficiency and anaphylactoid transfusion reaction: a case report.

Anaphylactoid transfusion reaction following the administration of incompatible blood products can be life threatening, but accounts for only a very small proportion of all transfusion reactions. One of the causes of anaphylactoid transfusion reaction is the reaction of patient's anti-immunoglobulin A(IgA) with plasma IgA which is usually present in transfused blood. We report a case who had anaphylactoid transfusion reactions after transfusion of only a few milliliters of packed RBC from 3 consecutive donors, in spite of compatible pretransfusion crossmatches. The patient's serum revealed IgA deficiency accompanied by high-titer anti-IgA. The family study showed that one of her sons had partial IgA deficiency accompanied by anti-IgA2. In conclusion, although selective IgA deficiency is rare in Taiwan, it may still occasionally result in severe anaphylactoid transfusion reactions.

Aged↗
PubMed1996

[Solitary plasmacytomas of bone and extramedullary plasmacytomas].

Among plasma cell disorders, solitary plasmacytoma (solitary plasmacytoma of bone, SPB and extramedullary plasmacytoma, EMP) is rare as compared with multiple myeloma (MM). Furthermore, the relationship between solitary plasmacytoma and MM remains unclear. Between 1960 and 1994, 24 patients with SPB and 20 with EMP were treated. The criteria for diagnosis were: (1) no evidence of other lesions based on clinical and radiologic examinations; (2) biopsy evidence of a plasma cell neoplasm; (3) bone marrow biopsy specimen with negative findings (less than 10% plasma cells); (4) no anemia, hypercalcemia or renal involvement. The average follow-up period was 112 months (from 6 to 360 months). Fifty-four percent of patients with SBP and 40% of patients with EMP developed MM, however, there was no significant statistical difference between SPB and EMP (P > 0.05). We suggested that solitary plasmacytomas be classified as two types, latent and aggressive. The former was histologically well-differentiated plasmacytoma. The latter was poorly differentiated tumors which easily progress to MM. The treatment of choice is wide excision or thorough curettage, by cryogenic necrosis with liquid nitrogen or cautery of the bony wall with phenol and the cavity filled with bone grafts or cementation. All patients with apparently isolated plasmacytoma should receive local radiotherapy after operation. Adjuvant chemotherapy should be given if the tumour turns out to be poorly differentiated, in order to delay their progression to MM.

Adult↗
PubMed1996

[Detection of bacterial vaginosis in gram stained vaginal smears and papanicolaou stained cervical smears].

OBJECTIVE: To determine the sensitivity and specificity of diagnosis of bacterial vaginosis (BV) by papanicolaou (PAP)-stained cervical smears and gram-stained vaginal smears according to clinical criteria. METHODS: In the prospective study of 196 non-pregnant women of child-bearing age, 94 were clinically diagnosed to have BV. Gram-stained vaginal smears and PAP-stained cervical smears were collected from all enrolled patients. RESULTS: In comparison with clinical diagnosis of BV, the sensitivity and specificity of gram-stained vaginal smears and PAP-stained cervical smears were 94.7% (89/94), 98.0% (100/102) 85.1% (80/94), and 95.1% (97/102). The characteristics of BV in gram-stained vaginal smears and PAP-stained cervical smears included small bacteria of Gardnerella and bacteroides morphotypes and curved gram variable rods and absence of bacteria of Lactobacillus morphotypes. CONCLUSION: It is possible to screen and manage BV according to Gram-stained vaginal smears or PAP-stained cervical smears.

Adult↗
PubMed1996

CY/TBI-800 as a pretransplant regimen for allogeneic bone marrow transplantation for severe aplastic anemia using HLA-haploidentical family donors.

Allogeneic BMT is the treatment of choice for patients with SAA who have an HLA-identical sibling donor. The results, however, have been relatively poor for transplants from partially matched family donors or unrelated donors because of the high incidence of graft rejection and/or GVHD. Six multiply transfused patients received a novel conditioning regimen of CY 200 mg/kg and TBI 800 cGy prior to receiving marrow from their HLA-haploidentical family donors. Three recipient-donor pairs were mismatched for one HLA locus, one for two loci and two for three loci. A combination of MTX and CsA was used for GVHD prophylaxis. Engraftment was noted in all six patients. Acute GVHD occurred in four patients, two each for grade I and II, respectively. One patient, who was ABO-compatible with her donor had delayed onset of pure red cell aplasia (PRCA) which completely recovered 6 months after additional immunotherapy with prednisolone. There were two deaths; both occurred while patients were on treatment for GVHD. One was from systemic fungemia and the other probably from cytomegalovirus interstitial pneumonitis (CMV-IP). Four patients (66.7%) have been alive and disease-free for more than 8.2, 27.3, 38.4 and 47.2 months after BMT, respectively. The results suggest that CY/TBI-800 may be a simple and effective conditioning regimen for SAA patients receiving BMT from family members other than HLA-identical siblings.

Adolescent↗
PubMed1996

[Role of area postrema on DOCA-salt induced hypertension in rat].

OBJECTIVE: To determine the effect of area postrema AP on DOCA-salt induced hypertension in rat, with emphasis on renal hemodynamics. METHOD: Blood pressure, salt and water balances and renal hemodynamics were observed in AP ablated and sham-operated rats treated with DOCA-salt. RESULTS: In AP intact (API) rats, after one week of DOCA-salt treatment BP began elevating to statistical significance at the end of the second week (MAP 15.9 +/- 0.7 vs. 13.5 +/- 0.5 kPa), followed by a plateau period from the third to fifth week. In AP ablated (APX) rats, BP raised during the first week of DOCA-salt treatment. However, the elevation gradually disappeared and BP returned to baseline at the fifth week. Sodium balance study showed that DOCA-salt treatment induced significant sodium retention in API rat, while the sodium metabolism remained stable in APX group except in the first week. Basal renal hemodynamic parameters (GFR, RPF, UNaV, UV) were not changed at neither the beginning nor the end of the study. However, a small dose of hypertonic saline (7% NaCl 0.3 ml) injection caused a brisk rising of these four parameters in APX but not API group. CONCLUSION: AP plays an important role in normal salt and water metabolism and might be involved in pathogenesis of DOCA-salt hypertension through regulation for renal hemodynamics and body fluid homeostasis.

Animals↗
PubMed1996

[Intraluminal stent and balloon of intraluminal stent for prevention of esophageal stenosis due to alkali corrosive injury: experimental and clinical studies].

Experimental and clinical results of a intraluminal stent and ballon of intraluminal stent to prevent scar stenosis after esophageal corrosive injury. The model of Davis's esophageal corrosive injury was used. The dogs in group II III IV were killed at 7 weeks after injury. The smallest diameter of esophagus in group III and IV was significantly larger than that in group II (P < 0.01). The collagen content in group III and IV was significantly lower than that in group II (P < 0.01) and it was still lower in group IV than in group III (P < 0.05). Esophageal compoiance in group III and IV was significantly greater than that in group II (P < 0.01) and it was still greater in group IV than in group III (P < 0.05). The analyses of collagen images showed that the collagen density in group II (P < 0.01) was further lower IV than that in group III (P < 0.05). In 18 cases who were treated for prevention of stricture formation with an intraluminal stent 10 cases were completely recovered, 6 recovered after repeated dilations, and 2 failed. Furthermore, all 5 cases treated with mechanical pressure intraluminal stent were successful. It is suggested that intraluminal stent and mechanical pressure of intraluminal stent can alleviate the corrosive stenosis. But the balloon of intraluminal stent is still better than the intraluminal stent.

Adolescent↗