Biomedical subjects
Publications and source records attributed to T Sekine.
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.
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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.
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.
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.
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.
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.
Highly stereoselective synthesis of (2'R)-[2'-2H]-2'-deoxyribonucleosides (2'R:2'S = > 99:1) were accomplished by treating 2'-bromo-3',5'-O-TPDS-2'-deoxyribonucleosides with tributyltin deuteride at lower temperatures such as -60 degrees C in the presence of triethylborane. Moreover, synthesis of some oligodeoxyribonucleosides involving them will be described.
Three-dimensional morphology and neuromuscular junctions of the branched muscle fibers of the rat skeletal muscles isolated from the rat were examined by application of the nitric acid digestion method for scanning electron microscopy. Treatment with fifteen percent nitric acid and a supersonic wave bath were effective in isolating the branched muscle fibers and for detecting their innervations by scanning electron microscopy. Mean numbers of total and branched fibers in the rat plantaris muscles were 11,130 +/- 314 and 32.4 +/- 4.8 (n = 12), respectively. Bifurcation of these fibers resembled either the letter X (X type) or letter Y (Y type). The Y type fibers were most frequently seen (84% of total branched fibers), and X types accounted for 14%. The remaining 2% of the fibers were subtypes of X and Y with overlapping bifurcation. These branched fibers were differentiated by their length from the bifurcated point, i.e., short, medium and long branches. Neuromuscular junctions on these branched fibers were located almost at the center of their length. The number of innervations was decided by the number of bifurcating fibers across the central part of the length.
Peripheral blood lymphocytes separated from about 20ml of blood were cultured with immobilized anti-CD3 antibody and IL-2. Total T lymphocytes in the culture expanded about 2,000 times by 2 weeks culture. Expanded T lymphocytes were infused to cancer patients, and safety and feasibility was confirmed. This method will be applicable for prevention of cancer recurrence.
From 1986 to 1992, seventeen patients with recurrent intrapelvic malignancies have been treated with intraoperative radiotherapy (IOR) in Saitama Cancer Center. They were 8 males and 9 females. The age ranged 44 to 83 (mean:61.6). The primary organs involved were rectum in 7, urinary bladder in 5, uterine cervix in 3 and ovary in 2. Invasion of recurrent disease into bony pelvis was noted in all but one patient. A total of 27 IORs were done on 18 occasions for 17 patients. The mean radiation dose was 25.6 Gy (range: 12-30). The cones used were 4 to 7 (mean: 5.4) cm in diameter. Debulking surgery was performed in 13 patients just before IOR. Chemotherapy and/or external radiotherapy were done in addition to IOR in most of the cases. As of May 1992, 14 patients had died with a mean survival time of 10 months (range:0.5-29.8). IOR seems to be useful in controlling the intrapelvic recurrent disease and may warrant further investigation.
Time density curve (TDC) can be reconstructed from the data of intravenous digital subtraction angiography (IVDSA). We evaluated peak time (PT) and modal transit time (MOTT) of the TDC as the probable indicator of cerebral intravascular blood flow. Cerebral IVDSA and single photon emission CT (SPECT) were performed on 12 patients of ischemic cerebrovascular disease, which consisted of 3 internal carotid artery (ICA) occlusions, one middle cerebral artery (MCA) occlusion, one anterior cerebral artery (ACA) branch occlusion and 7 lacunar infarctions. We classified former 4 patients as occlusion group and latter 8 as reference group. In 3 patients (2 ICA and one MCA occlusions), SPECT study revealed definite hypoaccumulation in the MCA territory of occlusive side. Two regions of interest (ROI) were placed on the territories of right and left middle cerebral arteries in the frontal view of cerebral IVDSA. Digital data processor fitted gamma curve to the TDC of each ROI, and calculated PT and MOTT. The absolute lateralities of PT and MOTT of MCA territory was significantly (p less than 0.05) larger in occlusion group than reference group. Patients with hypoaccumulation in SPECT had significantly (p less than 0.02) larger laterality of MOTT than patients with isoaccumulation. One ICA occluded patient without hypoaccumulation in corresponding MCA territory had relatively small laterality of MOTT similar to the patients of ACA branch occlusion and lacunar infarction. These results suggest that PT and MOTT are possible to detect the laterality of the intravascular blood flow in MCA territories caused by major artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
A patient with intravascular hemolysis due to residual shunt after patch closure of VSD was presented. The patient was 31-day-old female. She underwent VSD closure with Dacron patch 2 weeks after the initial operation (subclavian flap method) for coarctation concomitant with VSD. Soon after the operation, severe intravascular hemolysis and hemolytic anemia appeared. Conservative therapies were not effective, and her general condition got worse gradually. Forty days after closure of VSD, she underwent reoperation and the shunt was closed. Hemolysis disappeared dramatically. It was suggested that early reoperation was necessarily when severe intravascular hemolysis due to residual shunt after patch closure of VSD had persisted.
Indium-111-labeled tumor-infiltrating lymphocytes (111In-TIL) were transferred as an intrahepatic arterial bolus to determine their in vivo distribution in patients with hepatic malignancies. In the in vitro culture system, TIL were expanded upon simultaneous stimulation by recombinant interleukin-2 (rIL-2) and immobilized anti-CD3 monoclonal antibody. This double activation led not only to a larger cell yield, but also to a significantly more dominant subpopulation with CD4+ phenotype than occurred with activation by rIL-2 alone. Accumulations of 111In-TIL in the liver were identified by scintigraphy in all of three patients, corresponding to the tumor localization by computed tomography. Such accumulation had persisted for at least 48 hours after infusion. After intraarterial chemoimmunotherapy that included TIL, two of three patients achieved a partial therapeutic response. The authors conclude that their method of culture and transfer can facilitate the accumulation of TIL at tumor sites, which may augment the antitumor effects of adoptive immunotherapy.
Two novel flavonol triglycosides, camelliaside A and B, have been isolated from seeds of Camellia sinensis. The structures were determined to be kaempferol 3-O-[2-O-beta-D- galactopyranosyl-6-O-alpha-L-rhamnopyranosyl]-beta-D-glucopyranoside and kaempferol 3-O-[2-O-beta- D-xylopyranosyl-6-O-alpha-L-rhamnopyranosyl]-beta-D-glucopyranoside on the basis of spectroscopic, chemical and enzymatic studies. These types of interglycosidic linkages, Gal(1----2)[Rha(1----6)]Glc and Xyl(1----2)[Rha(1----6)]Glc, have not been reported previously in flavone and flavonol glycosides.
Cross-linking of effector T cells to target cancer cells augments their tumor lytic activities. Here we describe a new method of conjugating lymphokine-activated killer (LAK) cells with cancer-specific monoclonal antibody. The LAK cells were biotinylated, treated with avidin, and conjugated with biotinylated monoclonal antibody. These monoclonal antibody-conjugated LAK cells showed specifically enhanced killing activities against anti-tumor antibody-reactive cancer cells, and cold target cells specifically inhibited their activities.
Localization of tumor markers in human renal cell carcinomas (RCC) was studied by an immunohistochemical method using 12 different monoclonal antibodies (MAbs) recognizing carbohydrate antigens, and 2 polyclonal antibodies against S-100 protein and neuron-specific enolase (NSE), respectively. 115D8, DF3 and the MAb to epithelial membrane antigen (EMA) reacted with 9 of 13 (115D8), 6 of 13 (DF3) and 5 of 12 (MAb to EMA) cases of RCC, respectively. S-100 protein was also found in 10 of 13 cases of RCC. Further immunohistochemical studies showed that tumor cells of all 13 RCCs were strongly positive for NSE. Serum NSE levels of patients with RCC were examined by radioimmunoassay. This examination revealed that increased levels of NSE were detected in 11 of 17 sera of patients with RCC. Positive rates for patients in stages II, III and IV were 100% (10/10). On the other hand, increased levels of CA15-3 were detected in only 2 of 17 sera by enzyme immunoassay. Our results indicate that NSE may be a useful marker for human RCC, especially for those tumors that have broken through the renal capsule.
Pepleo-jelly, peplomycin (PEP) compounded with sodium polyacrylate (PANa), was used as a local preoperative chemotherapy for esophageal cancer. Thirty milligrams of PEP emulsified in 10 ml of jelly was orally administered for 17 patients on consecutive bed time, and the average total dose was 470 mg. Concentrations of PEP in blood and tissue were measured with a bioassay. PEP was not detected in the blood but was detected in esophageal tissue and regional lymphnodes. A significant difference (p less than 0.05) of tissue concentrations between normal esophageal mucosa (0.11 microgram/g) and malignant region (0.34 microgram/g) was noted. Furthermore, PEP was detected in many regional lymphnodes. Histological antitumor effect (Ef2) was noted in three of the eight metastatic lymphnodes. A side effect of this treatment was not recognized. It is believed that this treatment is safe and useful in combination with other adjuvant cancer therapy.