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Biomedical subjects

S Negoro

Publications and source records attributed to S Negoro.

At least 163 records · Page 9Linked to original sources
PubMed1987

Development of selective IgM deficiency in systemic lupus erythematosus patients with disease of long duration.

Statistical analysis of serum immunoglobulin levels in 54 systemic lupus erythematosus (SLE) patients showed a decrease in serum IgM (normal 77 +/- 26 mg/dl; P less than 0.001) that was closely related to disease duration. The longer the duration of SLE, the more striking the decrease in serum levels of IgM (r = -0.74, P less than 0.01). Selective IgM deficiency (less than 47 mg/dl) occurred in SLE patients whose disease was clinically inactive or less active.

Adolescent↗
PubMed1987

Functional interleukin 2 receptors on B cells lacking Tac antigens.

Human B lymphoblastoid line, SKW 6-4, cells were induced to IgM-secreting cells by high concentrations of interleukin 2 (IL 2). These cells were found to be unreactive with anti-Tac antibody and did not express mRNA detectable for Tac antigen. In Scatchard plot analysis, low-affinity IL 2-binding sites were found on SKW 6-4 cells. Moreover, analysis of the IL 2-binding molecules revealed ones (molecular weight 70,000 and 75,000) distinct from Tac antigen. It is conceivable that IL 2 exerts its effect through its interaction with these novel IL 2-binding molecules in SKW 6-4 cells.

Antigens, Surface↗
PubMed1987

Methylation of c-myc gene changes in human lymphoproliferative diseases.

The degree of methylation at the c-myc proto-oncogene was found to change in human lymphoproliferative diseases, when examined using a methylation-sensitive restriction enzyme. In peripheral blood mononuclear cells (PBMC) c-myc DNA showed hypomethylation in human lymphoproliferative diseases, in comparison to normal subjects matched in age and sex. In cases of chronic lymphocytic leukemia (CLL), the change was amplified in the crisis. When the DNA was examined at the actin gene, no significant change was observed. The results suggest that the change in c-myc protooncogene methylation might become an important clue in understanding the relationship between levels of gene expression and methylation in human lymphoproliferative diseases.

DNA↗
PubMed1987

Age-related changes of the function of T cell subsets: predominant defect of the proliferative response in CD8 positive T cell subset in aged persons.

The proportion of CD8 positive cells in the peripheral blood AET-rosette forming T cells from aged persons was significantly reduced than that from young persons. The difference in the proportion between aged and young groups became more significant after proliferative response to a mitogen phytohemagglutinin (PHA) or a specific antigen tuberculin active peptide (TAP). The purified macrophage-deprived T cells (Twp), CD4 (T4) positive cells or CD8 positive cells were prepared from aged or young persons. These cell preparations lost proliferative response to PHA or TAP but showed marked proliferative response to the combined stimulation to 1 microM of ionomycin and 1 nM of phorbol-12-myristate-13-acetate (PMA) at usual culture cell density (2.5 X 10(5)/ml). Proliferative responses of these cell preparations to the combined stimulation were significantly reduced in the aged than those in the young and the magnitude of the difference in the proliferative responses between aged and young groups was more pronounced in CD8 positive cell population than in CD4 positive cell population. Although the cell preparations were relatively independent of exogenous IL-2 for the proliferative response to the combined stimulation of ionomycin and PMA at usual culture cell density, they needed exogenous IL-2 for sustained proliferation at lower culture cell density (5 X 10(3)/ml). These IL-2-dependent proliferative responses to the combined stimulation in the aged were significantly lower than those in the young and again the difference in the proliferative magnitude between aged and young groups was greater in CD8 positive population. The mechanism(s) of age-related change of the proportion and proliferative ability of T subsets were discussed.

Adult↗
PubMed1987

Age-associated changes in proliferative and differentiative response of human B cells and production of T cell-derived factors regulating B cell functions.

The abilities of highly purified B cells to repeat replication for clonal expansion and to differentiate into immunoglobulin secreting cells (ISC) were examined in the aged and young groups. B cells from the aged showed twofold less proliferative response to B cell mitogen Cowan 1 (SAC) than those from the young. The original clone size of SAC responding B cells determined by colchicine block and [3H] thymidine [( 3H] TdR) uptake was not significantly reduced in the aged whereas the ability to repeat replication to expand clonal size was significantly reduced. B cells from aged and young persons were induced into ISC by combined stimulation with SAC and partially purified B cell differentiation factor (BCDF) free of IL-2 activity. ISCs for IgG and IgA were rather increased or at least not reduced in number in the aged as compared with those in the young. We also determined the IL-2 and BCDF activity produced by T cells from aged and young persons. Upon PHA stimulation, the aged T cells produced tenfold less IL-2 activity and threefold higher BCDF activity than did young T cells. Approximately threefold increase in spontaneous secretion of BCDF activity by aged T cells was found as compared with young T cells. The inverse correlation between the IL-2 activity and BCDF activity was found when both activities were determined in the same samples.

Adult↗
PubMed1987

Protooncogene expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus as an indicator of the disease activity.

In the present study, we examined the various protooncogene expressions in PBMC (peripheral blood mononuclear cell) of systemic lupus erythematosus (SLE) patients to determine if they could be an indicator for the disease activity. We divided SLE patients into "very active," "active," and "remitting" states according to the clinical symptoms in addition to the laboratory data peculiar to SLE. In addition, we determined the amount of circulating immune complex (IC) as one of the representative laboratory indicators for the disease activity. We found a positive correlation with either c-myc or c-myb expression and the amounts of IC and clinical disease activity. The degree of c-myc and c-myb expression was significantly reduced along with or prior to the amelioration of clinical symptoms and improvement as determined by laboratory data under treatment with prednisolone and/or azathioprine administration. The degree of c-myc and c-myb gene expression had no direct relation to the presence of particular clinical sign(s) or autoantibody. The expression of the c-raf gene was found in SLE and other systemic autoallergic patients although it showed no correlation with the disease activity. No significant expression of c-src, c-ras, c-fos, c-fgr, c-fps, c-fes, c-fms, c-yes, c-rel, c-abl, c-mos, c-sis, and c-erb B genes was found in the patients. c-myc and c-myb expression as having pathogenic and clinical significance is discussed.

Antigen-Antibody Complex↗
PubMed1987

[Serial measurements of serum carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) during chemotherapy of patients with inoperable lung cancer].

Serial measurements of serum CEA levels were analyzed in 226 patients with inoperable lung cancer (115 small cell carcinomas, 64 adenocarcinomas, 37 squamous cell carcinomas and 10 large cell carcinomas) during chemotherapy. Of all patients, 29.1% had pretreatment CEA levels greater than or equal to 5 ng/ml. In all of the patients with complete response, and 15 (68.2%) of 22 patients with partial response whose pretreatment CEA levels were 5 ng/ml or higher, CEA levels fell to below 5 ng/ml. All of 17 patients who showed a decrease greater than 50% in serum CEA levels during chemotherapy showed a shrinkage of more than 50% in the tumor burden. Serial serum CEA level measurements were useful as an indicator of response to chemotherapy in advanced lung cancer. Serial serum NSE levels were measured in 36 patients with small cell lung cancer. Pretreatment NSE levels were elevated to more than 10 ng/ml in 83.1% of all patients. A transient rise in serum NSE levels occurred in 22 out of 33 patients measured on the third day during initial chemotherapy. Serum NSE levels greater than or equal to 10 ng/ml declined to within the normal range in all patients responding to the chemotherapy. The survival in patients whose NSE levels (greater than or equal to 10 ng/ml) fell to within the normal range for more than four weeks was longer than that in other patients. Serial measurements of serum NSE levels were thus useful for monitoring the response to chemotherapy in cases of small cell lung cancer.

Adenocarcinoma↗
PubMed1987

[Studies on the appropriate administration of cisplatin based on pharmacokinetics and toxicity].

Ninety-six patients with non-small cell lung cancer were treated with cisplatin (80-150 mg/m2). The pharmacokinetics of cisplatin were studied in 27 of these patients. Cisplatin was administered intravenously for 30-120 min. Plasma concentrations of total platinum and ultrafilterable (non-protein-bound) platinum were monitored by flameless atomic absorption spectrophotometry. Maximum total platinum levels in plasma were attained at the end of infusion, and thereafter decayed in a biphasic fashion, with an initial phase half-life (t1/2 alpha) of 10.2 to 14.6 min and a secondary phase half-life (t1/2 beta) of 41.7 to 81.3 h. The half-life was prolonged as the dosage was increased. Non-protein-bound platinum was rapidly cleared to below the measurable level within 4 hours at 80 mg/m2 and 120 mg/m2 of cisplatin, but declined in a biphasic manner, with t1/2 alpha of 31.2 min and t1/2 beta of 20.1 h at 150 mg/m2 of cisplatin. Toxicities were increased according to dosage, and decreased with a 50 mg/m2 X 3 days regime. Nephrotoxicity and ototoxicity were the dose-limiting factors in the single-dose escalation scheme used. In conclusion, the optimal dosage of cisplatin appeared to be 120 mg/m2 considering its toxicity.

Adult↗
PubMed1986

Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified Tac-positive T cells.

Proliferative response of T cells from aged persons was significantly reduced to a specific antigen tuberculin-active peptide (TAP) determined by [3H]TdR uptake and FCM in comparison to that from the young. Cytokinetic analysis for the proliferative response to TAP showed that, in the aged, the clonal size or the number of the first generation responding cells to TAP was not significantly reduced but the ability to repeat replication was more profoundly affected. Neither the delayed entry into the cell replication nor prolongation of the cell cycle time could explain these results. Similar results have been reported on the proliferative response of T cells to mitogen: PHA (Phytohemagglutinin). Expression of Tac-antigen on T cells determined by anti-Tac antibody binding with FACS after stimulation with either TAP or PHA was found to be reduced significantly in the aged. Both the numbers of high and low affinity IL-2 receptors determined by radiolabelled IL-2 binding assay were also reduced in the aged, but the degree of reduction in number of high affinity ones was more pronounced than that in low affinity ones. Tac-positive T cells were isolated with the use of anti-Tac rosette methods and stimulated with recombinant IL-2 (r-IL-2). Their proliferative response was significantly lower in the aged than that in the young at any concentration of r-IL-2 examined. The number of the first generation responding cells to r-IL-2 in purified Tac-positive T cells from the aged was 82% of that from the young whereas the proliferative response by aged T cells was 39% of that by young ones when the cells were allowed to repeat replication for 3 days. The mechanisms of these multifactorial defects in proliferation of T cells from aged persons were discussed.

Adult↗
PubMed1986

Structure of a beta-galactosidase gene of Bacillus stearothermophilus.

The nucleotide sequence of the bgaB gene, which encodes the thermostable beta-galactosidase I of Bacillus stearothermophilus, and its flanking region was determined. A 2,016-base-pair open reading frame observed was concluded to be for beta-galactosidase I (Mr 78,051) from observations that the amino acid composition of the enzyme and the sequence of 14 amino acids from the amino-terminus of the enzyme coincided with those deduced from this open frame. A 107-base-pair HaeIII-AluI fragment just upstream of the estimated Shine-Dalgarno sequence of the bgaB gene had promoter activity toward cat-86 (chloramphenicol acetyltransferase gene) and produced the enzyme at a level equivalent to 7% of the total cellular protein of B. subtilis. From the base sequence of this DNA region and the transcriptional start site determined by S1 nuclease mapping, the -35 and -10 sequences are estimated to be TTGACA and TAATTT, respectively, which are similar to the consensus sequence of B. subtilis sigma 43 RNA polymerase.

Amino Acid Sequence↗
PubMed1986

Alternating non-cross resistant chemotherapy for small cell lung cancer.

After stratification for the extent of disease, previously untreated patients with small cell lung cancer randomized to receive therapy with the four-drug combination of cyclophosphamide, oncovin, nimustine hydrochloride (ACNU), and procarbazine (CONP) every four weeks (continuous regimen) or to receive CONP alternating with the three-drug combination of etoposide (VP-16), adriamycin and cisplatin (VAD) at four-week intervals (alternating regimen). Sixty-nine patients were entered in the study. Of 34 evaluable patients receiving the continuous regimen, six (17.6%) achieved complete response (CR) and 16 (47.1%) achieved partial response (PR). Of 31 evaluable patients receiving the alternating regimen, 10 (32.3%) achieved CR, and 16 (51.6%) achieved PR. There was a tendency in favor of the alternating regimen in CR and over-all response rates (0.05 less than p less than 0.1). There were no significant differences between the regimens in response duration or survival. The projected median survival times were 9.2 months and 9.4 months for the continuous and alternating regimens, respectively. One patient receiving the continuous regimen and three receiving the alternating regimen have been living for more than two years. The major toxicity was myelosuppression in both regimens. One patient died of hemorrhage due to thrombocytopenia during induction with CONP, and one patient died of cisplatin-induced renal failure. We conclude that alternating non-cross resistant chemotherapy leads to improved CR and response rates, but does not improve survival.

Adult↗
PubMed1985

High Production of Thermostable beta-Galactosidase of Bacillus stearothermophilus in Bacillus subtilis.

By cloning the beta-galactosidase gene of Bacillus stearothermophilus IAM11001 (ATCC 8005) into Bacillus subtilis, enzyme production was enhanced 50 times. beta-Galactosidase could be purified to 80% homogeneity by incubating the cell extract of B. subtilis at 70 degrees C for 15 min, followed by centrifugation to remove the denatured proteins. Because of its heat stability and ease of production, beta-galactosidase is suitable for application in industrial processes.

Journal Article↗
PubMed1985

Altered expression of cell surface membrane antigens in a common acute lymphoblastic leukemia-associated antigen-expressing neuroblastoma cell line (SJ-N-CG) with morphological differentiation.

The expression of common acute lymphoblastic leukemia antigen (CALLA) on a human neuroblastoma cell line, SJ-N-CG, was demonstrated by indirect membrane immunofluorescence, complement-dependent cytotoxicity, and quantitative absorption, using two monoclonal antibodies (J-5 and BA-3) directed against CALLA. Immunoprecipitation of solubilized 125I-labeled membrane proteins from SJ-N-CG cells with J-5 antibody revealed a protein with a molecular weight of 100,000 as determined on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Morphological differentiation of SJ-N-CG cells could be induced in the presence of 2.0 mM dibutyryl adenosine 3'-5'-cyclic monophosphoric acid for 10 days of culture. Changes in cell surface membrane antigens associated with morphological differentiation were studied by indirect immunofluorescence and complement-dependent cytotoxicity using a panel of seven monoclonal antibodies. Increases in the antigens recognized by BA-2 (detecting leukemia-associated antigen), anti-Thy-1, and antibody 390 (Thy-1 antigen) were found in "differentiated cells," while those detected by BA-1 (B-cell-associated antigen) and J-5 (CALLA) were unchanged. In contrast, the antitransferrin receptor defined by B3/25 was inhibited, and expression of B7/21-defined la-like antigen was not induced. Kinetic studies on antigenic alterations showed that the expression of BA-2-defined antigen rose on Day 2 and remained at the same level until Day 10. The expression of CALLA was not changed from Days 2 to 10. The augmentation of Thy-1 antigen was noted on Day 4 and reached the maximum on Day 10. These results show that dibutyryl adenosine 3'-5'-cyclic monophosphoric acid is capable of inducing phenotypic changes in SJ-N-CG cells. The changes of expression of some antigens on exposure of cells to dibutyryl adenosine 3'-5'-cyclic monophosphoric acid may enable us to have a greater understanding of the differentiation of neuroblastoma to a more mature ganglioneuroblastoma phenotype.

Antibodies, Monoclonal↗
PubMed1985

[Phase II study of cis-dichlorodiammineplatinum (II) for non-small cell lung cancer].

A phase II study of cis-dichlorodiammineplatinum (II) (CDDP) was performed in 83 patients with inoperable non-small cell lung cancer (21 squamous cell carcinomas, 57 adenocarcinomas and 5 large cell carcinomas). CDDP was given by i.v. infusion at a dosage of 50 mg/m2 (low-dose regimen) or 80-100 mg/m2 (high-dose regimen) every 3 to 4 weeks. Seventy-nine out of 83 patients were evaluable for tumor response. Sixteen of these evaluable patients achieved complete or partial response, and the overall response rate was 20.3%. The response rates were 27.8% in patients with squamous cell carcinoma and 19.6% in those with adenocarcinoma. None of the patients with large cell carcinoma responded. The high-dose regimen was superior to the low-dose regimen in response rate (25.6% versus 5.8%). The responders survived significantly longer than patients with NC (p = 0.02) or PD (p = 0.003). Leukopenia of less than 3000/mm3 occurred in 12.1% of cases, and thrombocytopenia of less than 7 X 10(4)/mm3 occurred in 7.6%. A transient elevation of serum creatinine value was observed in 9 patients (10.8%). Moderate to severe nausea and/or vomiting occurred in almost all patients. It was therefore considered that CDDP was one of the most effective agents for non-small cell lung cancer with tolerable toxic effects.

Adenocarcinoma↗
PubMed1985

Induction of persistent autoimmune haemolytic anaemia in mice by combined use of rat erythrocyte preimmunization and chronic GVHR.

Female F1 mice (BDF1: C57BL/6 x DBA/2, BCF1: C57BL/6 x C3H/HeN, BBF1: C57BL/6 x BALB/c) were preimmunized with rat erythrocytes and then received splenic T cells from parental female C57BL/6 mice injected with hydrocortisone acetate before killing. In BDF1 and BCF1 mice, direct Coombs' test (DCT) positivity persisted for more than 4 months in almost all mice. They also showed haematological sign of anaemia, and the survival of infused 51Cr-labelled parental C57BL/6 erythrocytes was reduced. In BBF1 mice, DCT positivity returned to negative within 2 months. Autoantibodies were eluted from DCT-positive erythrocytes and their specificities were examined. They were capable of binding equally well to erythrocytes from all strains of mice tested, including the donor mice. They also cross-reacted with rat erythrocytes but not with sheep, rabbit or human erythrocytes. Isotypes of the autoantibodies eluted were also examined. Interestingly, isotypes of the autoantibodies obtained from individual mice were confined to one or other subclass of IgG isotype: IgG1, IgG2a or IgG2b.

Anemia, Hemolytic, Autoimmune↗
PubMed1985

[Response and pharmacokinetics of cisplatin instilled into the pleural cavity].

The response and pharmacokinetics of cisplatin instilled into the pleural cavity were studied in 11 patients with malignant pleural effusion; 10 patients had primary lung cancer and one had breast cancer. All of them were adenocarcinoma histologically. In five of the 11 patients effusion disappeared and its cytology became negative for malignancy after four weeks. In the other six patients effusion was reduced and its cytology became negative for malignancy after four weeks. Toxicity was almost similar to that in systemic administration of cisplatin but a few patients had chest pain and fever possibly due to local irritation. The pharmacokinetics showed that a high concentration of cisplatin (free-form, 48.9 micrograms/ml) was maintained over a long period (free from (t 1/2) beta = 33.6 hours) in the pleural cavity. This was regarded as the reason for the high response to this therapy. The intrapleural instillation of cisplatin into the pleural cavity therefore seems to be an effective modality for malignant pleural effusion.

Aged↗