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Biomedical subjects

T Sekine

Publications and source records attributed to T Sekine.

At least 145 records · Page 8Linked to original sources

A feasible method for expansion of peripheral blood lymphocytes by culture with immobilized anti-CD3 monoclonal antibody and interleukin-2 for use in adoptive immunotherapy of cancer patients.

Cultivation of T lymphocytes with immobilized anti-CD3 monoclonal antibody and human recombinant interleukin-2 induced a rapid proliferative response. This procedure was applied to expansion culture of peripheral blood lymphocytes obtained from cancer patients for use in adoptive immunotherapy. Peripheral blood mononuclear cells were separated from 20 ml of blood and cultured in anti-CD3 coated flasks with rIL-2 for 6 days, then transferred to a gas-permeable culture bag and culture continued for an additional 8 days with an increasing volume of medium. Cell numbers increased about 2000-fold during this 2-week culture. The final population contained about 30% CD4+ and 60% CD8+ cells, and all were CD3+ & HLA-DR+. NK cells comprised less than 5%. In clinical trials involving 12 cases receiving 35 infusions, the mean number of harvested T cells after 14 days culture was 3.5 x 10(10) (R = 1.6-6.8 x 10(10)), and the mean expansion index was 1560-fold (R = 409-4091). This method could be of benefit not only in immunotherapy but also for obtaining somatic cells from a small volume of blood for use in molecular or genetic analysis instead of having to perform EB virus transformation of B cells.

Antibodies, Monoclonal↗

Isolation of camelliaside C from "tea seed cake" and inhibitory effects of its derivatives on arachidonate 5-lipoxygenase.

A new flavonol glycoside, camelliaside C, was isolated from "tea seed cake" prepared from the defatted seeds of Camellia sinensis O. Kuntze. The structure was determined as kaempferol 3-O-beta-D-galactopyranosyl-(1-->2)-beta-D-glucopyranoside by spectroscopic methods (FAB-MS, UV, IR, 1H- and 13C-NMR) and the enzymatic transformation of camelliaside C to astragalin. Camelliaside C showed an inhibitory effect on the arachidonate 5-lipoxygenase of RBL-1 cells (IC50:1.4 x 10(-4)M) as did camelliaside A and B isolated from the same product.

Animals↗

Absolute configuration of L-methionine sulfoximine as a toxic principle in Cnestis palala (Lour.) Merr.

An unusual amino acid, L-methionine sulfoximine (1), has been isolated from the fresh seeds of Cnestis palala (Lour.) Merr. [Connaraceae]. The absolute configuration of the natural sulfoximine (1) was confirmed to be 2(S)-methionine S(S)-sulfoximine [(2S,SS)-2-amino-4-(S-methylsulfonimidoyl)-n-butanoic acid] by comparison of the [alpha]D value and IR spectrum with those of authentic samples obtained through the optical resolution of synthetic materials. Acute toxicity of the seeds of C. palala in a beagle dog was also studied.

Animals↗

[A new lupin alkaloid, (-)-leontalbinine N-oxide, in Sophora flavescens var. angustifolia seeds and its synthesis by biomimetic transformation from (+)-matrine N-oxide].

The possibility of the biomimetic transformation of (+)-matrine N-oxide, a main alkaloid in Sophora flavescens var. angustifolia, under various oxidative conditions was examined by the use of several metallic ions. When (+)-matrine N-oxide was warmed with FeSO4, or Fe(COOH)2 in MeOH-H2O at 40 degrees C, (-)-7, 11-didehydromatrine [(-)-leontalbinine], a minor alkaloid in the same plant, was obtained along with (+)-matrine. This selective formation of (-)-leontalbinine seems to be specific to the reaction of (+)-matrine N-oxide with ferrous reagents. In addition, the structure of the newly isolated minor lupin alkaloid from the seeds of S. flavescens. was determined as (-)-leontalbinine N-oxide from its spectral comparison with the authentic sample.

Alkaloids↗

A case-control study of colorectal cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan.

A case-control study of colorectal cancer in relation to dietary, smoking, and drinking habits was undertaken in Saitama Prefecture, Japan. The study was based on 181 newly diagnosed cases of adenocarcinoma of the colorectum at a single institution and 653 general population controls. Dietary habits were investigated on the basis of the intake of 12 foods and 12 food groups in a food intake frequency questionnaire, together with individual food preferences. Preference for salty foods was positively related to the risk of both colon and rectal cancer, and the consumption of seaweed was inversely related to these cancers, both with a dose-response relation. Cigarette smoking was inversely related to colon cancer risk, but not to rectal cancer risk. Alcohol intake tended to be associated inversely with colon cancer, but not with rectal cancer. In the multiple logistic regression, preference for salty foods (positively) and the consumption of seaweed (inversely) were independently related to both colon and rectal cancer risks.

Adenocarcinoma↗

CD7, CD4 and myeloid antigen-positive acute lymphoblastic leukemia.

We report a case of acute lymphoblastic leukemia (ALL, FAB-L2) with unique cellular characteristics. Leukemic cells were negative for various cytochemical stainings except acid phosphatase. Immunophenotypic studies revealed CD7+, CD4+, CD8-, CD2+, CD3-, CD13+, CD25+, CD33+ and CD34+. The immunoglobulin heavy chain and T-cell receptor beta, gamma and delta chain genes were germline configurations. This patient had a karyotype of complex abnormalities involving Nos. 5 and 7. Leukemic cells showed a prominent response to interleukin-3, granulocyte macrophage colony stimulating factor (GM-CSF) and G-CSF with partial granulocytic differentiation in a colony assay. A binding assay confirmed the presence of both high and low affinity receptors for GM-CSF. These findings suggest that CD7+CD4+CD8-CD3- putative T-cell precursors may retain the capacity to differentiate to myeloid lineage.

Antigens, CD↗

Chromosome 3p deletion in a renal cell carcinoma cell line established from a patient with von Hippel-Lindau disease.

von Hippel-Lindau disease (VHL) is an autosomal dominant inherited disease, frequently accompanied by occurrences of renal cell carcinoma (RCC). Both the VHL gene and tumor suppressor genes for RCC have been mapped to the short arm of chromosome 3, although the genes have not yet been identified. An RCC cell line, KC12, was established from a VHL patient. Molecular genetic analyses in conjunction with cytogenetic studies revealed that the short arm of chromosome 3 distal to the D3S4 locus at 3p11 was lost in the RCC cell line as a result of an unbalanced translocation between chromosomes 3p and 5q. Structural and numerical aberrations, including those on chromosome 3p, were not detected in T-lymphocytes from the patient, suggesting that the inherited mutation of the VHL gene at 3p25-26 in this patient was too subtle to be detected by either Southern blot or karyotype analysis. Since no permanent RCC cell line has been established from a VHL patient, this cell line will be a useful source for analyzing the VHL gene at 3p25-26 and tumor suppressor gene(s) at 3p13-21.

Adult↗

Precise analyses of DNA structure by NMR.

Novel 1H NMR techniques were developed and applied to the analyses of the DNA structure. They distinguished the base proton signals of cytosine (uracil) from those of the other bases. Two dimensional experiments were also performed by using these techniques, and were found to be useful for signal assignments. Moreover, the (2'R)-[2'-2H]-labeled DNA 10-mer and 17-mer were synthesized to be used for the determination of precise structures. These stereoselective [2'-2H]-labeling made possible explicit stereospecific assignments and exact determination of the vicinal coupling constants, 3JHH, and thus the conformation of each deoxyribose ring was accurately determined.

Cytosine↗

[A case of intercostal neuropathy (Th 2-9) due to sarcoidosis].

Neurosarcoidosis is a disorder which presents in 5 percent of cases of general sarcoidosis, in only 10% of which the peripheral nerves are involved. A patient who complained of numbness of the abdomen and back associated with paralytic motion of intestines was admitted. The patient was diagnosed as having neurosarcoidosis of the intercostal nerves (Th2-9) on the basis of abnormality of somatosensory evoked potentials (SEP) and reduced conduction velocity, and evident disease of intrathoracic lesions confirmed by biopsy. Corticosteroid was administered, with relief of symptoms and active response on SEP. Somatosensory evoked potentials and VC were of great value in the diagnosis and follow up of peripheral neuropathy due to sarcoidosis.

Evoked Potentials, Somatosensory↗

DNA analysis of two patients with a non-fluorescent Y chromosome.

Results of DNA study on two patients of gonadal dysgenesis with a 45,X/46,X,Ynf (non-fluorescent Y chromosome) karyotype are described. In one patient who developed gonadoblastoma, all 12 loci on the non-fluorescent part of Yq were detected. Another patient did not have gonadoblastoma at 20 years, and only the proximal 6 loci out of 12 were detected.

Adult↗

A role for protein kinase C in the growth of human erythroid progenitor cells.

We searched for a possible role for protein kinase C in the growth of human erythroid progenitor cells, using pharmacologic approaches. Two protein kinase C inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and staurosporine, dose-dependently inhibited the growth of immature erythroid progenitor cells (BFU-E) induced by interleukin 3 (IL-3) plus erythropoietin (Ep) or granulocyte macrophage colony-stimulating factor (GM-CSF) plus Ep whereas a weaker analog of H-7, N-(2-guanidinoethyl)-5-isoquinoline sulfonamide (HA-1004), had no effect on the number of BFU-E. These three compounds had no effect on the growth of mature erythroid progenitor cells (CFU-E) stimulated by Ep. The culture of accessory cell-depleted bone marrow demonstrated that the effects of these compounds on colony formation do not appear to be mediated by accessory cells. The potential of these compounds to inhibit the GM-CSF-dependent growth of KG-1 cells correlated well with the extent of their inhibitor of protein kinase C activities from KG-1 cells. Thus, the protein kinase C system is apparently involved in the growth of BFU-E, supported by IL-3 or GM-CSF. The growth signal for CFU-E transduced by Ep may be achieved through other systems.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells.

The expression of interleukin-2 receptors (IL-2R) was examined in 328 adult patients with non-T-cell (non-T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti-Tac for IL-2R alpha chain (IL-2R alpha) and Mik beta 1 for IL-2R beta chain (IL-2R beta). Leukaemic cells in the following cases were positive for anti-Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML-BC, 4/28 CD19(+)CD10(-) acute lymphoblastic leukaemia (ALL), and 20/64 common ALL (c-ALL). IL-2R beta was not detected on leukaemic cells of any case examined. Eleven of IL-2R alpha(+) AML were derived from myelodysplastic syndrome. None of the IL-2R alpha positive leukaemic cells responded to exogenous recombinant human IL-2 (rhIL-2) in culture. In addition, IL-2R alpha expression on non-T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL-2R alpha was demonstrated in the IL-2R alpha(+) patients examined. Clinically, the IL-2R alpha(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL-2R alpha(-) patients. Our results clearly indicate the diagnostic importance of IL-2R alpha expression in non-T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.

Acute Disease↗

Multivariate analyses of CT findings in typical schizophrenia and atypical psychosis.

In order to investigate the brain morphological differences between typical schizophrenia and atypical psychosis, the brain CTs of 41 patients with typical schizophrenia, 27 patients with atypical psychosis (ATP), and 20 controls were examined. The schizophrenics had larger values for 9 CT indices, i.e., interhemispheric fissure (IHF) index, VBR, 2 lateral ventricles (L-V) and 3rd ventricle (III-V) indices, and 4 sylvian fissure (SF) indices, while the values of ATP patients for 3 SF indices were greater than for the controls. Moreover, the schizophrenics had greater III-V and L-V indices than the ATP patients. The correlation matrix of CT indices indicates that the III-V index correlated well with the other CT indices, whereas the VBR, IHF and right SF indices did not. Therefore, it was speculated that there might be 3 subgroups, each of which has a main focus of alteration in the above-mentioned regions. Therefore, all the cases were divided by means of a cluster analysis into 5 groups. Group I, which contained mainly normal controls, and Group II, which consisted mainly of atypical psychosis patients, had no abnormal CT findings. Group III, which comprised mainly ATP patients and paranoid type schizophrenics, had right SF enlargement. Group IV, which showed significant IHF enlargement, and the residue group, which had larger VBR and significant left SF enlargement, consisted mostly of schizophrenics. Thus, our results suggest that the classification by CT data corresponds on the whole to our clinical diagnosis, according to which schizophrenic psychosis is divided into typical schizophrenia and atypical psychosis, and that each of the two psychosis groups may be further classified into distinct subgroups.

Adult↗

Regulation of differentiation and proliferation of rat hepatocytes by lactose-carrying polystyrene.

We noticed that hepatocytes recognize the structure of oligosaccharides via asialoglycoprotein receptors and synthesized lactose-carrying styrene polymer (PVLA) as an asialoglycoprotein model. We found that the regulation of differentiated function and proliferation of hepatocytes that were cultured on polystyrene dishes can be achieved by varying the amount of PVLA coated on the dishes. The 3H-thymidine uptake of cultured hepatocytes is low for cells cultured on dishes coated with high amounts of PVLA in which the hepatocytes are round and is highest for those cultured on dishes with a low PVLA coating level in which the hepatocytes are spread in shape. Moreover, bile acid release as a typical differentiated function of hepatocytes was maintained at higher levels in hepatocytes attached on dishes coated with a high level of PVLA. Our results indicated that regulation of differentiated function and proliferation in hepatocytes could be achieved by specific ligand-mediated recognition of microscopic surface structure. Thus, it may be possible to regulate proliferation and differentiation of hepatocytes by design of the culturing substrata.

Animals↗

Characterization of immobilized anti-CD3 antibody-activated T lymphocytes for use in adoptive immunotherapy of patients with brain tumors.

Large numbers of T lymphocytes were successfully cultured for use in adoptive immunotherapy using immobilized anti-CD3 antibody. This method allows more than 1.5 x 10(10) T lymphocytes to be cultured within 2 weeks from only 20 ml of blood. Proliferated T lymphocytes were less cytotoxic than lymphokine-activated killer cells induced with a high dose of interleukin-2, but were more specific for autologous tumor cells as determined by cold target competition. Signal transduction of anti-CD3 antibody induced a population of CD8 positive cells, i.e. cytotoxic T lymphocytes. Adoptive immunotherapy using autologous lymphocytes requires a sufficient number of lymphocytes and high induced cytotoxic activity. This method is promising for clinical adoptive immunotherapy of patients with brain tumors.

Adult↗