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Biomedical subjects

Y M Chen

Publications and source records attributed to Y M Chen.

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

Superior vena cava syndrome caused by encapsulated pleural effusion.

Pleural effusion is often a manifestation of the superior vena cava (SVC) syndrome. However, pleural effusion has never been reported to be a cause of the SVC syndrome. We report the case of a 68 yr old male patient who presented with SVC syndrome and respiratory failure, both attributable to an encapsulated pleural effusion over the right upper mediastinum. Simple drainage was performed as a diagnostic and therapeutic procedure. The pleural effusion was confirmed to be a tuberculous empyema. Chest computed tomography (CT) scan is the most appropriate initial diagnostic procedure for superior vena cava syndrome.

Aged↗
PubMed1997

Gemcitabine versus the combination of cisplatin and etoposide in patients with inoperable non-small-cell lung cancer in a phase II randomized study.

PURPOSE: A phase II randomized study was conducted to evaluate the efficacy and toxicity of gemcitabine (GEM) versus the combination of cisplatin and etoposide (EP) in Chinese patients with inoperable (stage III or IV) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From March 1995 to February 1996, 53 patients were enrolled onto the study: 27 onto the GEM arm and 26 onto the EP arm. In the GEM arm, gemcitabine 1,250 mg/m2 was given as a 30-minute intravenous (i.v.) infusion on days 1, 8, and 15 of each 28-day cycle. In the EP arm, cisplatin 80 mg/m2 was given on day 1 and etoposide 80 mg/m2 was given on days 1, 2, and 3 of each 28-day cycle. RESULTS: Twenty-six patients are assessable for treatment response on the GEM arm and 24 on the EP arm. Five patients (19.2%) on the GEM arm and five patients (20.8%) on the EP arm achieved a partial response (PR). No complete responses were attained on either treatment arm. All patients enrolled onto the study were eligible for toxicity assessment. The main toxicities were myelosuppression and vomiting, which included World Health Organization (WHO) grade 3 or 4 leukopenia (3.7%), thrombocytopenia (7.4%), anemia (7.4%), and nausea/vomiting (3.7%) on the GEM arm, and WHO grade 3 or 4 leukopenia (30.8%), thrombocytopenia (7.7%), anemia (15.4%), and nausea/vomiting (34.6%) on the EP arm. The median survival time was 37 weeks on the GEM arm and 48 weeks on the EP arm. CONCLUSION: Gemcitabine is a well-tolerated chemotherapeutic agent for NSCLC. The antitumor activity was promising, with a 19.2% single-drug response rate, when compared with EP combination chemotherapy, which had a response rate of 20.8%. The safety profile is better than that of EP treatment.

Adult↗
PubMed1997

Cross regulation by IL-10 and IL-2/IL-12 of the helper T cells and the cytolytic activity of lymphocytes from malignant effusions of lung cancer patients.

STUDY OBJECTIVE: Our previous report demonstrated that there was impairment of local cellular immunity with elevated interleukin-10 (IL-10) and undetectable IL-12 in neoplastic pleural effusion. These findings suggest that the local immune reactions favor the T-helper type 2 (Th2) pathway instead of Th1 pathway. The present study was designed to examine whether local cellular immunity could be manipulated by IL-2 and/or IL-12 treatment, and to determine their effect on the helper T-cell pathways and the cytolytic activity of the effusion-associated lymphocytes (EALs). DESIGN: Using malignant pleural effusions obtained from four patients suffering from adenocarcinoma of lung, we separated the tumor cells from the EALs with Ficol-Hypaque centrifugation, followed by Percoll density centrifugation. To test whether the cytolytic function of lymphocytes could be enhanced by culturing with IL-2 and/or IL-12, lymphocytes were incubated with recombinant IL-2 with/without IL-12 for 6 days. Following this, the tumoricidal activity was assessed in an overnight 5'chromium-release assay. Autologous tumor cells for measuring specific antitumor activity, Daudi cells susceptible to lymphokine-activated killer cells, and NK-susceptible K562 cells were used as target cells. MEASUREMENTS AND RESULTS: After treatment in vitro with IL-2, IL-12, or IL-2 plus IL-12, the Th pathway shifted from Th2 to Th1 type (increased gamma-interferon production). To further study the effect of cytokine treatment on the cytolytic activity of EALs, it was found that after 6-day culturing, the EALs failed to kill any of the three tumor targets, whereas the 6-day cultured peripheral blood lymphocytes (PBLs) gave low level of cytotoxicity against all three tumor targets. Stimulation with IL-2 alone partially restored the immunocompetence of EALs to kill the tumor targets. Stimulation with IL-12 alone showed no significant effect on their cytolytic activity. However, IL-12 synergized with IL-2 to increase the cytolytic activity of EALs and PBLs against autologous tumor targets. This synergistic effect was not found for Daudi cells and K562 cells. CONCLUSIONS: These results suggest that EALs activated with IL-12 in the presence of a low concentration of IL-2, which converted the EALs from Th2 pathway to Th1 pathway, could be an alternative source of antitumor effectors for adoptive immunotherapy of cancer.

Adenocarcinoma↗
PubMed1997

Molecular subtyping of the HIV-1 V3 loop sequences detected in HIV-1-positive patients in southern Taiwan.

Polymerase chain reaction and nucleotide sequence analysis were performed to amplify and determine the V3 loop sequences of human immunodeficiency virus type 1 (HIV-1) from ten seropositive patients at National Cheng Kung University Hospital, Tainan. The nucleotide sequences and the deduced amino acid (a. a.) sequences of these V3 regions were compared with those of known HIV-1 prototypes. The V3 loop a. a. sequences detected in eight individuals belong to subtype B which predominates in North America and Europe, whereas two individuals were infected with HIV-1 subtype E which is mainly found in the heterosexual populations of Thailand. Sequence analysis of these variant HIV-1 strains revealed a number of interesting features and a phylogenetic tree was also constructed according to the V3 loop nucleotide sequences of these variant strains and HIV-1 isolates from other parts of the world. Furthermore, our results suggest that the north vs south geographical separation in terms of HIV-1 epidemiology in Taiwan is insignificant.

Amino Acid Sequence↗
PubMed1997

Experience with ifosfamide and etoposide combination chemotherapy in extensive-disease small-cell lung cancer.

BACKGROUND: Ifosfamide, an isomeric analogue of cyclophosphamide, has significant activity against many human tumors including lung cancer, testicular cancer, lymphoma and sarcoma, and may be superior to its analogue. Herein, we report our preliminary experience using ifosfamide and etoposide (IE) combination chemotherapy in previously untreated patients with extensive-disease (ED) small-cell lung cancer (SCLC). METHODS: Patients with histologically or cytologically confirmed SCLC, measurable or assessable ED, no previous chemotherapy or thoracic irradiation, younger than 70 years of age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-3, and adequate marrow, liver, and renal functions were eligible for treatment which consisted of ifosfamide 2.0 g/m2/d given intravenously (i.v.) for 3 days with mesna 400 mg/m2/dose i.v. administered 0, 4, and 8 hours after the daily administration of ifosfarnide, and etoposide 80 mg/m2/d i.v. given for 3 days in every 4 weeks for a maximum of 6 cycles. RESULTS: Between January 1994 and February 1995, 10 patients were enrolled into the treatment. All were men with a mean age of 63 +/- 6 years. Five patients had an ECOG PS of 0 or 1, 4 patients of 2, and 1 patient of 3. A total of 45 cycles of IE were given. The mean number of cycles per patient was 4.5 +/- 2.1. Six patients completed 6 courses of therapy. Thirty-two of 45 cycles (71%) of IE were given at full doses, while the remaining 13 cycles (29%) were given at 75% of doses. Nine patients were assessable for response. Eight patients had a partial remission and one patient had stable disease. The overall response rate was 89%. The median survival was 8 months (range, 0 to 23 months) and the median failure-free survival duration was 5.5 months (range, 0 to 18 months). The 1- and 2-year survival rates were 30% and 0%, respectively. Myelotoxicity was the most important toxicity, particularly neutropenia, while thrombocytopenia and anemia were mild. Five of 10 patients (50%) experienced grade 4 neutropenia, which occurred in 2 patients during the first course of IE and resulted in one patient death from early sepsis. Other nonhematologic toxicities were mild. CONCLUSIONS: Our preliminary experience demonstrates that ifosfamide is an active drug against SCLC and combination chemotherapy with IE results in similar response rate and median survival, but probably higher myelotoxicity than reported studies in patients with ED SCLC.

Aged↗
PubMed1997

Frequency of the CCR5 delta 32 mutant allele in HIV-1-positive patients, female sex workers, and a normal population in Taiwan.

A specific 32-nucleotide deletion mutant of the CCR5 gene (Accr5), the coreceptor gene for human immunodeficiency virus type 1 (HIV-1), can effectively suppress the transmission and pathogenesis of the virus. Individuals homozygous for the delta ccr5 allele resist primary macrophage-tropic HIV-1 infection, despite multiple high-risk sexual exposures. This gene deletion is relatively common among Caucasians but uncommon among Africans, Asians, and South Americans. We used polymerase chain reaction (PCR) technology to determine the frequency of the delta ccr5 allele in a Taiwanese population with diverse health status and social backgrounds. Subjects included 24 HIV-1-infected persons in the northern and southern parts of Taiwan; 131 HIV-1 high-risk, licensed female sex workers in the northern part of the island (21% of whom were aborigines); and 187 unrelated, healthy, HIV-1-negative individuals in southern Taiwan. PCR with primers encompassing the entire CCR5 gene was used to explore possible deletions at regions other than the 32-nucleotide area in the female sex workers. No ccr5 deletions were detected, indicating that they are rare or absent in the Taiwanese population. This finding implies that delta ccr5 is not likely to be part of the defense against the spread of HIV-1-infection in Taiwanese.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins.

The Krüppel-associated box A (KRAB-A) domain is an evolutionarily conserved transcriptional repressor domain present in approximately one-third of zinc finger proteins of the Cys2-His2 type. Using the yeast two-hybrid system, we report the isolation of a cDNA encoding a novel murine protein, KRAB-A interacting protein 1 (KRIP-1) that physically interacts with the KRAB-A region. KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys3HisCys4, family of zinc binding proteins whose other members are known to play important roles in differentiation, oncogenesis, and signal transduction. The KRIP-1 protein has high homology to TIF1, a putative modulator of ligand-dependent activation function of nuclear receptors. A 3.5-kb mRNA for KRIP-1 is ubiquitously expressed among all adult mouse tissues studied. When a GAL4-KRIP-1 fusion protein is expressed in COS cells with a chloramphenicol acetyltransferase reporter construct with five GAL4 binding sites, there is dose-dependent repression of transcription. Thus, KRIP-1 interacts with the KRAB-A region of C2H2 zinc finger proteins and may mediate or modulate KRAB-A transcriptional repressor activity.

Amino Acid Sequence↗
PubMed1996

A dominant mutant form of the herpes simplex virus ICP8 protein decreases viral late gene transcription.

The herpes simplex virus (HSV) infected cell protein 8 (ICP8) is required for viral DNA replication and normal viral gene expression. Previous work in our laboratory has shown that ICP8 may play a role in stimulating late gene expression. In V2.6 cells which express the d105 mutant form of ICP8, synthesis of late proteins and accumulation of the late gC mRNA are reduced during HSV infection (Gao, M., and Knipe, D.M., J Virol. 65, 2666-2675, 1991). To determine if the negative effect of d105 ICP8 on the late gene expression was exerted at the transcriptional level, we measured the levels of mRNAs and transcription from three late genes, gC, UL47, and gD, in V2.6 cells and Vero cells infected with the HSV-1 wild-type virus. In infected V2.6 cells, the levels of late gC and UL47 mRNA were 7- to 12-fold lower than those of infected Vero cells under conditions where the levels of viral DNA replication in these two cell types were similar. The transcription levels of these two late genes in infected V2.6 cells were reduced to similar extents (9- to 14-fold). The levels of accumulated mRNA and transcription of the early-late gD gene also showed parallel reductions in infected V2.6 cells (about 6-fold). In contrast, transcription of the beta pol gene was reduced only slightly (about 2-fold) by d105 ICP8. These results demonstrate that the d105 ICP8 inhibits expression of three viral late genes at the transcriptional level, and in general, the effect of d105 ICP8 on viral gene expression appears to correlate with the extent to which expression of the gene is stimulated by viral DNA synthesis.

Animals↗
PubMed1996

Characterization of the replicon of plasmid pSW500 of Erwinia stewartii.

A 1.6-kb DNA region required for the replication of pSW500 from Erwinia stewartii SW2 has been identified. DNA sequencing analysis revealed that this DNA fragment consists of a DnaA box, seven 16-bp direct repeats, and a 1005-bp open reading frame. The seven direct repeats have been demonstrated to mediate the incompatibility function of the plasmid. Primer extension analysis showed that the 1005-bp ORF is transcribed in vivo and the +1 site of the transcript is located 113 bp upstream from the translation initiation codon of the ORF. Complementation studies showed that this ORF is required for the replication of the plasmid and may encode a replication protein, RepA. Gene fusion studies revealed that the expression of repA is autoregulated by RepA. We also found that the pSW500 replicon has a copy number of approximately two and that the plasmid is stably maintained in Escherichia coli, thus demonstrating that the replicon contains all the elements required for copy number control and plasmid stability in E. coli. Curing of pSW500 from E. stewartii SW2 revealed that loss of pSW500 did not have any obvious effect on morphology or physiology of the cells, suggesting that pSW500 does not encode a function that is indispensable for the survival of the organism.

Amino Acid Sequence↗
PubMed1996

A population-based epidemiological study of human T-cell leukemia virus type I infection in Kin-Hu, Kinmen.

Kinmen is a group of small islands located between Taiwan and Fu-Kien Province of mainland China. The general population in Kinmen are descendants of immigrants from mainland China who began arriving around 317 A.D. Since it has been reported that 0.48% of adults in Taiwan have HTLV-I infection, the decision was made to conduct a community-based epidemiological study in Kinmen to understand the origin and dissemination of HTLV-I in north-east Asia. Over 68% of residents of Kin-Hu township in Kinmen over 30 years of age participated in this study. Eight of 1,425 males and 14 of 1,595 females had HTLV-I infection. Antibody reactivities were further tested by Western blot assays with HTLV-I or HTLV-II type-specific recombinant envelope glycoproteins, and it was determined that all of those infected had HTLV-I and none had HTLV-II. Logistic regression was used for multivariate analysis. The final model indicated that the significant factors associated with HTLV-I infection in Kinmen were age and coastal residency. Age was positively correlated with HTLV-I infection. The eastern coastal area had a rate of HTLV-I infection 3.1 times higher than other areas in Kin-Hu. Further genetic analysis in Kinmen is needed to elucidate a relationship with other HTLV-I isolates in the world.

Adult↗
PubMed1996

Cytotoxic effects of gemcitabine-containing regimens against human non-small cell lung cancer cell lines which express different levels of p185neu.

A novel pyrimidine analogue, gemcitabine, has been found to inhibit DNA replication and repair. We speculated that gemcitabine in combination with DNA-damaging agents might be more active against high- than low-p185neu expressing non-small cell lung cancer (NSCLC) cells because the high-p185neu expressors were proposed to posses a more effective DNA repair ability. We therefore compared the combination effects of gemcitabine plus cisplatin, gemcitabine plus etoposide, and cisplatin plus etoposide in a panel of 12 NSCLC cell lines. We also investigated the correlations between the level of p185neu and the cytotoxicities of each single agent and the three combinations. We found that as single agents the cytotoxicities of cisplatin and etoposide but not gemcitabine were significantly correlated with the level of p185neu. In contrast to the tight cross-resistance between cisplatin and etoposide, gemcitabine demonstrated little cross-resistance to either etoposide or cisplatin. Both gemcitabine-containing combinations demonstrated equivalent or more active cytotoxicities compared to cisplatin plus etoposide, with gemcitabine plus cisplatin showing a greater synergistic activity which was effect (dose) dependent. The effect of cisplatin plus etoposide was not p185neu related, whereas gemcitabine-containing regimens, especially gemcitabine plus cisplatin, had a greater cytotoxicity against the high- than the low-p185neu expressors. Our findings indicate that gemcitabine in combination with cisplatin is active against NSCLC cells in vitro. The gemcitabine-cisplatin interaction is more active than the etoposide-cisplatin interaction in cells with high-p185neu expression.

Antimetabolites, Antineoplastic↗
PubMed1996

Serum cytokine level fluctuations in chemotherapy-induced myelosuppression.

We have reported that serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) levels rise in patients with chemotherapy-induced myelosuppression. The aim of the present study was to determine whether other cytokines that function at different hematopoietic stages also fluctuate during chemotherapy-induced myelosuppression and whether the extent of cytokine level fluctuations correlate with myelosuppression severity. Fifteen patients participated in the study. Serum levels of stem cell factor (SCF), interleukin (IL)-1 alpha, IL-6, IL-3, granulocyte-macrophage CSF (GM-CSF) and G-CSF were analyzed before chemotherapy and during the myelosuppressive stage and correlations between cytokine levels and myelosuppression severity were examined. The results showed that both serum G-CSF and IL-6 levels rose in patients with chemotherapy-induced myelosuppression. The prechemotherapy serum G-CSF and IL-6 levels correlated well with their respective elevated levels during the myelosuppressive stage. The myelosuppression severity also correlated well with the extent of serum G-CSF level elevation. The serum IL-6 and G-CSF levels during the myelosuppressive stage correlated significantly. Serum SCF levels did not fluctuate significantly during myelosuppression, and IL-1, IL-3 and GM-CSF were rarely detected in serum even after chemotherapy. In the present study, the roles of IL-1 alpha, SCF, IL-3 and GM-CSF chemotherapy-induced myelosuppression were not clear.

Adolescent↗
PubMed1996

Shortened survival of lung cancer patients initially presenting with pulmonary tuberculosis.

It has been reported that the incidence of lung cancer is higher in patients with pulmonary tuberculosis (TB). However, there is little information on the survival and clinical characteristics of these patients. We retrospectively reviewed the medical records of patients with coexisting pulmonary TB and lung cancer covering a period from 1988 to 1994. There were 31 such patients among a total of 3928 lung cancers diagnosed. Lung cancer patients had an increased risk of active pulmonary TB in comparison with the general population in Taiwan. Diabetes mellitus (DM) was found in 37.5% of patients who were diagnosed as having active pulmonary TB within 2 years before, or concurrent with, the diagnosis of lung cancer. However, none of the patients who had developed lung cancer before TB had a history of DM. Epidermoid carcinoma accounted for 64.5% of these cases. The patients who had developed active pulmonary TB before, or concurrently with, the diagnosis of lung cancer survived shorter than those who did not have pulmonary TB at diagnosis of lung cancer (P=0.007). Survival from diagnosis of pulmonary TB was longer in patients who developed the disease earlier than lung cancer (P=0.046). Survival from the time of diagnosis of lung cancer was significantly longer in patients who developed cancer earlier than active pulmonary TB (P=0.0048), those without DM (P=0.0132), those with an early tumor stage (P=0.002), and those given specific cancer treatment (P=0.0001). It is concluded that survival is shorter in lung cancer patients who present initially with active TB than in those who do not have TB.

Aged↗
PubMed1996

Hydralazine inhibits human peritoneal mesothelial cell proliferation and collagen synthesis.

The integrity of the mesothelial layer is essential for both defence and solute transport in continuous ambulatory peritoneal dialysis (CAPD). The human peritoneal mesothelial cell (HPMC) culture has been shown to be a very useful tool to study the peritoneal mesothelial stem cell behaviour. We investigated whether hydralazine, an antihypertensive agent frequently used, might affect HPMC growth and collagen synthesis. HPMCs were cultured from specimens of human omentum by enzymatic disaggregation of omentum. HPMC growth was evaluated by modified methyltetrazolium (MTT) assay. Cell viability was confirmed by trypan blue exclusion and lactate dehydrogenase assay. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Intracellular cAMP levels were measured by enzyme immunoassay. The procollagen alpha 1 (I) mRNA expression was evaluated by Northern blot analysis. Hydralazine inhibited serum-stimulated HPMC growth in a dose-dependent manner. The maximal inhibition was 93% at a concentration of 100 micrograms/ml. Hydralazine inhibited collagen synthesis in confluent mesothelial cells (47% inhibition at a concentration of 100 micrograms/ml). The procollagen alpha 1 (I) mRNA expression was also decreased by hydralazine (about 50% decrease at 100 micrograms/ml). These effects may be due to the phosphodiesterase inhibition property of hydralazine to increase intracellular cAMP levels. These data suggest that the use of hydralazine in CAPD patients may affect peritoneal membrane function and integrity.

Antihypertensive Agents↗
PubMed1996

Fibroadhesive form of tuberculous peritonitis: chyloperitoneum in a patient undergoing automated peritoneal dialysis.

Chyloperitoneum is a rare condition in patients undergoing peritoneal dialysis. We report here a patient who developed chylous ascites during the course of tuberculous peritonitis. The diagnosis was confirmed by cultures of dialysate and peritoneal biopsy, and laparoscopy revealed severe hyperemia and intestine adhesion. Intrinsic lymphatic obstruction and superimposed peritoneal fibrosis together might be responsible for the pathogenesis of this special presentation. Although in most cases of continuous ambulatory peritoneal dialysis, the causes of chyloperitoneum remained unknown, we suggest, from the experience of this case, that tuberculous peritonitis, especially the fibroadhesive form, should be highly suspected in any dialysis cases with chyloperitoneum. Laparoscopy should be initiated early, particularly when the culture is negative for common pathogens or when the patient responds poorly to the usual antimicrobial agents.

Chylous Ascites↗