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Biomedical subjects

S Fan

Publications and source records attributed to S Fan.

At least 163 records · Page 9Linked to original sources
PubMed1990

Adaptive response to 2 low doses of X-rays in human blood lymphocytes.

Human peripheral blood lymphocytes exposed to a single adaptive dose of 1 cGy X-rays or 2 adaptive doses, each of 1 cGy, were found to be equally resistant to the induction of chromosome damage by subsequent challenge with a high dose of 1 Gy X-rays, as compared to cells that were not pre-exposed. They responded with a significantly reduced incidence of chromatid and isochromatid breaks. These results indicate the presence of an inducible chromosomal repair mechanism in human blood lymphocytes and confirm the observations made by earlier investigators. The incidence of chromosome damage was found to be similar in the lymphocytes pre-exposed to a single or 2 adaptive doses, suggesting that, under the conditions tested, the second adaptive dose did not offer any additional protection against the chromosome damage induced by the challenge dose.

Adult↗
PubMed1990

Changing of hepatitis B virus markers in patients with bone marrow transplantation.

The hepatitis B virus (HBV) infection and its resulting hepatic abnormalities are very high in prevalence among the Taiwan population. They also seem to compose a major problem to patients subjected to bone marrow transplantation (BMT) due to intensive chemoradiotherapy. In this study, the sera of 42 patients were investigated before and after BMT to detect the presence of HBV markers and to test their liver function (LF). Being followed-up for 3-12 months after BMT, 12 out of 27 were found to have altered HBV markers according to the classification of the following: seroconversion of HBsAg, clearance of HBsAb, appearance of HBeAg, clearance of HBeAb, and acute hepatitis. Thirty-seven out of 42 patients (88.1%) were found in routine LF test to develop one or more abnormality; however, 90% of them turned normal within one year after BMT. Only one patient died of complications associated with fulminant hepatitis. In conclusion, the previous hepatic damage from HBV infection appears unlikely to increase the risk of posttransplant morbidity and mortality.

Adolescent↗
PubMed1990

Remission induction of ANLL with low dose cytosine arabinoside combined with retinoic acid.

Fourteen cases of acute non-lymphocytic leukemia (ANLL) were treated with low doses of cytosine arabinoside (LDAra-C 20 mg/m/q12h) and etretinate (all-trans-9-3, 7-dimethyl-2, 4, 6, 8 non-atetraenoate, 75 mg/d). Of which 9 were untreated, 3 were in first relapse and 2 were refractory patients. Five of the 9 patients in the first group, and all 3 patients in the second group achieved complete remission (CR). The 2 cases with refractory ANLL showed no response. The CR rates in untreated, first relapse and refractory patients were 55.6%, 100%, and 0% respectively. In all, there was significant reduction of marrow cellularity in 13 patients, 5 of whom developed bone marrow aplasia with predominantly lymphocyte and plasma cells. Only 2 cases with M5 ANLL showed evidence of differentiating into monocytes and neutrophil in hypocellular marrow phase. The efficacy of this drug combination, however, appeared to be achieved through cytotoxicity rather than differentiation. The side effects in the treated cases included cheilitis, dermatitis, fever, petechiae, and impaired liver function, which soon improved upon discontinuation or reduction of dosage. This combination treatment might be most effective in achieving remission among elderly and severely infected patients with ANLL, and could be appropriate even for patients in first relapse.

Adolescent↗
PubMed1990

Generation of lymphokine-activated killer (LAK) cells and possible implications in autologous bone marrow transplantation--a preliminary report.

Lymphokine-activated killer (LAK) cells were generated successfully without mitogen from blood mononuclear cells obtained from 14 patients with varying malignancies and 2 normal donors. Cells from both groups showed a positive cytotoxicity by a 4-hour 51-Cr-release assay against a variety of target cells including natural killer (NK) sensitive K562 myeloid leukemia, NK-resistant Raji lymphoma cell lines, and fresh/cryopreserved leukemia cells from patients refractory to standard chemotherapy but not normal blood cells. Higher cytotoxic activity was obtained with a higher effector:target ratio at 100:1 greater than 50:1 greater than 25:1 (P less than 0.01) in each setting of different targets. Experiments involving cocultures of the LAK cells with either allogeneic (9) or autologous (3) bone marrow cells disclosed no detrimental effect on the committed hemopoietic stem cells by semisolid agar colony forming unit (CFU-GM) assay. The findings suggest that LAK cells may have a potential role for the in vitro purging of the residual leukemic cells from the marrow inoculum prepared for autologous bone marrow transplantation.

Adolescent↗
PubMed1989

Phosphorylation of cytoskeleton-associated proteins, pp58 and pp60, in tumouricidal murine peritoneal macrophages.

Two highly phosphorylated vimentin-like proteins, pp58 and pp60, are expressed in macrophages activated in vivo to tumouricidal activity. Resident and elicited, non-tumouricidal peritoneal macrophages displayed low and intermediate levels of phosphorylated pp58 and pp60, respectively. C3H/HeN macrophages became tumouricidal after incubation with 0.1 micrograms/mL A23187 plus 10 nmol/L 12-phorbol 13-myristate acetate (PMA), or 0.1 micrograms/mL A23187 plus 100 ng/mL lipopolysaccharide (LPS), and displayed increased phosphorylation of pp58 and pp60. LPS non-responder C3H/HeJ macrophages were not tumouricidal nor did they show increased phosphorylation of pp58 and pp60 after incubation with LPS plus A23187 in vitro. C3H/HeJ macrophages, however, did become tumouricidal and expressed increased phosphorylation of pp58 and pp60 after incubation with A23187 and PMA. Addition of PGE2 (10(-8) mol/L), resulted in down-regulation of macrophage tumouricidal activity and decreased pp58 and pp60 phosphorylation, which was reversed by addition of indomethacin (10(-6) mol/L) to cultures with PGE2. Phosphorylation increased within 5 min after adding activating stimuli while incorporation of [35S]-methionine into a 58 kD protein did not occur until 6 h later. No 60 kD protein synthesis was detected during the first 8 h after adding activating stimuli, indicating that previously synthesized proteins were phosphorylated during macrophage activation. These results signify a physiological role for the phosphorylation of cytoskeleton-associated pp58 and pp60 during macrophage activation to tumour cytotoxicity.

Animals↗
PubMed1989

The many faces of neuroblastoma.

Neuroblastoma is a common tumor in childhood. It arises in the adrenal gland or in various extraadrenal primary sites of the sympathetic chain. Clinically, it may present as an abdominal mass or as disseminated metastatic disease. We studied 52 patients with neuroblastoma, and the typical and unusual radiographic features of the disease are presented.

Adrenal Gland Neoplasms↗
PubMed1989

[Second primary cancer in hematological malignancy experience in VGH-Taipei].

Seven patients of hematological malignancy with second primary cancer had been found at Veteran General Hospital from 1983 to 1988. The second primary cancers either developed subsequently or concurrently with the hematological malignancies. Four patients were diagnosed to be non-Hodgkin's lymphoma and three of them developed squamous cell carcinoma of lung(2) and hepatocellular carcinoma (1) at 44, 20 and 45 months after the initial diagnosis of on-Hodgkin's lymphoma. All three had received chemotherapy and/or radiotherapy. Another one was found to have liposarcoma in the retroperitoneum concurrently. Three patients had chronic lymphocytic leukemia (CLL). Two of them were found to have skin squamous cell carcinoma at the same time. Another one developed cervical squamous cell cancer ten months after treatment with oral leukeran and prednisolone. Literature about synchronous and metachronous neoplasms was reviewed.

Adult↗
PubMed1989

Treatment of severe aplastic anemia: comparison of bone marrow transplantation to immunotherapy.

Between February 1985 and May 1988, sixteen patients with severe aplastic anemia (SAA) post multitransfusion were treated with either allogeneic bone marrow transplantation (BMT) (9) or immunosuppression (7). The latter group was further divided into two subgroups: horse anti-human thymocyte-lymphocyte globulin (ATG-ALG) (2) and high dose methylprednisolone (HDMP) (5). There were 8 males and 8 females, age ranged from 10 to 35 years for the BMT group and 19 to 56 for the immunosuppression group. As of analysis, 9 patients in the BMT group had been followed from 1 to 31 months after transplant (median,24). Graft rejection was noted in 2, both had positive mixed lymphocyte culture (MLC) index. Seven had full recovery of hematopoiesis. Of these 7 survivals, none developed acute graft-versus-host disease (GVHD), whereas 2 had chronic GVHD which resolved completely after a 9-month treatment with azathioprine and prednisolone. Kaplan-Meier survival probability at 31 month was 75%. In the immunosuppressive therapy group 2, who received ATG-ALG both failed the treatment, died 7 and 29 months later, respectively. There were 3 responders in the HDMP subgroup, 1 complete, 2 partial. The 1-year survival probability for this group was 42.9% compared with 75% in the BMT group (p greater than 0.10). However, the hematologic reconstitution and Karnofsky performance were complete in all 7 transplant survivals vs one of 3 in the immunosuppression group (p less than 0.01). This experience supports that for patients with SAA under the age of 40, BMT is the treatment of choice if an HLA-identical MLC-nonreactive marrow donor is available, if not, immunosuppression is an alternative approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Treatment of metastatic colorectal adenocarcinoma with fluorouracil and high-dose leucovorin: a pilot study.

In Veterans General Hospital-Taipei, 25 patients with metastatic or recurrent colorectal adenocarcinoma were treated with a 5-day course of 5-FU (370 mg/M2/d) and high dose leucovorin (200mg/M2/d), repeated every 28 days until a progression of disease was evident. Twenty-one patients had evaluate tumor response. Among the 16 patients with measurable disease, three patients achieved partial response (PR), and their response durations were 2 months, 6 months and 6+ months. Five patients had stable disease (SD) for 4,4,6,7, and 10 months before its progression. Among the 5 patients with documented abdominal carcinomatosis, four remained stable without any progression for 5,6,12 and 12 months after treatment. The overall response rate was 57% (3PRS, 9SDs). Seven of the 12 responders had prior 5-FU exposure. Nine patients had progressive disease and 7 of them died within a few months after the start of treatment. The median duration of response was 6.7 months. The median survival for responders was 9.8 months, and for non-responders, 3.7 months. Performance status (PS) was a main determinant of response. Among the patients with PS = 0 (6 patients), there were 2 PRs and 4 SDs and with PS = 1 (8 patients), 1PR and 4 SDs. When PS = 2 or 3 (7 patients), only 2 SDs were noted. All the 25 patients were put into toxicity test to find in a mild to moderate, easily controlled state. There were 3 (12%) patients with grade 2-3 mucositis, 6 (24%) with grade 2 diarrhea, 13 (50%) with nausea and vomiting. Only 3 cases developed leucopenia but without thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1985

Pharmacologic assessment of regimen chemosensitivity in the soft-agar assay: effect of oxygen on human tumors.

The influence of oxygen on the growth and the in vitro chemosensitivity of human tumor cells was studied in the soft-agar assay. Tumor cells of pancreatic and ovarian origin prefer a reduced oxygen atmosphere for colony formation, whereas those of pulmonary origin grow better in 20% oxygen. Depending on the physiologic oxygen tension and the histologic origin of a particular cancer type, the in vitro chemosensitivity of many drug obtained with the conventional culture system could be inadequately assessed. The in vitro responses of tumor cells to combinations of drugs were measured by the regimen efficacy index (REI) method. The REI delineates the possible regimen enhancement or regimen default based on the in vitro chemosensitivity of the individual agents tested in the assay. In vitro regimen enhancement was observed only in ascites incubated in a reduced oxygen atmosphere with two-drug combinations. However, regardless of the oxygen gradients used, regimen default was seen in cancer cells of solid tumors treated with all combinations of drugs tested. This study suggests further investigation on the effects of oxygen in the soft-agar assay, and proposes the novel use of the REI method for evaluating the in vitro regimen chemosensitivity of human tumor cells.

Antineoplastic Agents↗
PubMed1985

Cooperative evaluation of human tumor chemosensitivity in the soft-agar assay and its clinical correlations.

In supporting the human-tumor cloning effort of the Southwest Oncology Group, we conducted an independent retrospective study to evaluate the clinical correlations of the soft-agar colony-forming assay developed by Hamburger and Salmon (1977). This study was made with the cooperation of 76 clinicians and 11 hospitals in Greater New Orleans. In a 10-month trial (July 1982 to May 1983), we received 134 human tumors of 26 classifications and achieved 76% success in colony growth from 122 plated samples. Retrospective correlations between the in vitro chemosensitivity of tumor colonies and clinical drug responses were made possible in 31% of the patients. Evaluation of 45 in vitro and in vivo associations indicated a combined sensitivity of 0.65 and a specificity of 0.68 for the assay. Technical refinements and the selectivity of the assay are discussed.

Antineoplastic Agents↗
PubMed1984

Sectional analysis of tumor colony growth in the soft-agar assay: effects of oxygen.

Soft-agar clonogenicity of L1210 mouse leukemia cells and of xenografts of a human melanoma and a carcinoma of the cervix was studied sectionally by the sizes of the colonies grown under hypoxic gradients and aerobic condition. Soft-agar plating efficiency was increased in cultured L1210 cells with decreasing oxygen concentrations. The growth of both cultured L1210 cells and their BDF1 ascites was better in 5% oxygen than in 20% oxygen. Although soft-agar colony development of both melanoma and cervical carcinoma was significantly better in 5% oxygen, the former has a secondary preference for a hypoxic atmosphere and the latter, for an aerobic condition.

Animals↗
PubMed1983

A role for calcium-activated calmodulin in murine nonspecific cell-mediated cytotoxicity.

The role of Ca++ in mouse nonspecific cell-mediated cytotoxicity was studied using the calcium ionophore A23187, inhibitors of calmodulin activity, and agents which modulate cyclic AMP concentration. A23187 markedly enhanced spleen lymphocyte cytotoxicity against SV3T3 target cells, suggesting that Ca++ influx enhances cytolytic activity. This conclusion was supported by experiments in which verapamil, a Ca++ channel blocker, inhibited normal and ionophore-induced cytotoxicity. A23187 also enhanced cytolysis of YAC-1 cells in a 16-hr 51Cr release assay, but had little effect in the more typical 4-hr assay. Lysis of BHK, a cell line resistant to murine natural cytotoxicity, could not be induced by A23187. However, hamster effector cells, which can lyse xenogeneic target cells, showed increased against either SV3T3 or BHK. This indicates that the effect of the ionophore was not due to nonspecific release of toxic products from the effector cells. Both normal and ionophore-enhanced lysis were also inhibited by the phenothiazines chlorpromazine and trifluoperazine, which block the activity of calmodulin. A more specific calmodulin activity inhibitor, W13, was also shown to profoundly inhibit cytotoxicity induced by A23187. These results suggest that Ca++ acts as a stimulus-response coupler in cell-mediated cytotoxicity, and that calmodulin mediates the effects of the Ca++. Furthermore, cyclic AMP appears to modulate the action of Ca++ since agents which increase cAMP levels reduce the effects of A23187.

Animals↗
PubMed1975

Interaction of transition metal ions with ribonuclease A. II. The selective effects of Mn2+, Zn2+, Cd2+ and Hg2+ on the histidine magnetic resonance.

Zn2+, Cd2+ and Hg2+ inhibit ribonuclease but Mn2+ does not except at very high concentrations. By high resolution NMR one can detect in the pH range 5-8 the C-2 protons of histidines 105, 12, and 119. The inhibiting ions produce large shifts of the resonance of His-12 but not of His-105. On the other hand Mn2+ broadens the C-2 proton of His-105 much more than it does those of His-12 and 119. The selective shifts suggest that the mechanism of inhibition is binding at or near the active site of which His-12 and 119 are a part. The selective broadening is a consequence of binding of the Mn2+ to a site very far from the active site but closer to His-105.

Binding Sites↗
PubMed1975

Nuclear magnetic resonance study of ligand binding to Mn-aspartate transcarbamylase.

Aspartate transcarbamylase from Escherichia coli has been prepared with up to four of zinc ions replaced by manganese, and the effect of this substitution on the proton nuclear magnetic resonance properties of succinate bound to the catalytic site and of cytidine 5'-triphosphate bound to the regulatory site has been determined, The specific activity and allosteric properties of the Mn-substituted enzyme are essentially identical with those of the native enzyme. The longitudinal relaxation time, T1, of the succinate protons is shortened by the native enzyme and is shortened further by the Mn-substituted enzyme at both 100 and 220 MHz in D2O solutions of 0.02 M immidazole chloride (pH 7.0), 10 minus 3 M beta-mercaptoethanol, 0;2 mM ethylenediamenetetraacetic acid, and 2.5 mM carbamyl phosphate over a temperature range of 5 to 35 degrees. Under the same conditions, the transverse relaxation time, T2, of the succinate protons at 90 MHz is shortened to the same extent by native and Mn-substituted enzyme. The temperature dependence of the relaxation times indicates that the shortening of the transverse relaxation time is determened by the lifetime of bound succinate, whereas the further shortening of the longitudinal relaxation time by the Mn-substituted enzyme is due to dipolar relaxation, i.e. to the interaction between Mn and the succinate protons. The distance between the Mn and the protons of succinate bound to the enzyme can be calculated from the relaxation time measurements and is 15,3 A. The dipolar interaction correlation time which is needed for the calculation of this distance, was found to be 3.5 X 10 minus 9 sec from the frequency dependence of T1. The transverse relaxation time of the C-6 proton of CTP is shortened to the same extent by both the native and Mn-substituted enzyme in D2O solutions of 0.02 M imidazole chloride (pH 7.0), 10 MINUS 3 M beta-mercaptoethanol, 0.2 mM ethylenediaminetetraacetic acid, and 2.5 mM carbamyl phosphate over the temperature 5-30 degrees. Since the temperature depencece of the relaxation time indicates the relaxation is not exchange limited, the manganese must be too distant from the bound CTP for an appreciable interaction to occur. This requires that the manganese be greater than 20A from the CTP. These results are used together with other available structural data to construct a schematic model for aspartate transcarbamylase.

Aspartate Carbamoyltransferase↗