Biomedical subjects
Y Hara
Publications and source records attributed to Y Hara.
[Current status and problems in the diagnosis of pancreatic cancer].
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Purification and physicochemical characterization of murine T cell replacing factor (TRF).
Murine T cell replacing factor (TRF) was purified from a cellfree supernatant of a T cell hybridoma (B151K12) that constitutively produces TRF. Two assay systems for TRF activity were employed: 1) induction of anti-DNP IgG PFC responses in cultures of splenic B cells from DNP-KLH-primed BALB/c mice, and 2) induction of IgM PFC in chronic B cell leukemic cells (BCL1). The purification scheme consisted of ammonium sulfate precipitation, DEAE-cellulose chromatography, Blue-Sepharose chromatography, hydroxylapatite chromatography, gel permeation with fast protein liquid chromatography (FPLC), and disc polyacrylamide gel electrophoresis. Overall, TRF was purified approximately 34,000-fold with a maximum 3.8% recovery of activity, and the specific activity of the purified TRF was approximately 9.6 X 10(4) U/mg. The TRF that is active in these systems is distinct from the other lymphokines such as IL 1, IL 2, BCGFI (now known as BSFp1), and gamma-interferon. The TRF is extremely hydrophobic, with an apparent m.w. of 50,000 to 60,000 on gel permeation chromatography and 18,000 on SDS-PAGE under reducing conditions. Highly purified B151-TRF abrogated the activity by treatment with trypsin but not with RNase. Moreover, it bound to lima bean agglutinin-Sepharose specific for N-acetylgalactosamine residues, indicating that B151-TRF is a glycosylated glycoprotein containing N-acetylgalactosamine residues. The role of N-acetylgalactosamine residues on TRF activity was additionally substantiated by the fact that the addition of appropriate amounts of N-acetylgalactosamine in the assay systems for TRF preferentially induced a profound suppression for TRF-mediated PFC responses.
Role of N-acetyl-D-galactosamine residue on B151K12-derived T cell-replacing factor (B151-TRF) molecule in B cell-receptor binding and -stimulating activity.
The role of sugar moiety on T cell-replacing factor molecule derived from a monoclonal T cell hybridoma B151K12 (B151-TRF) was analyzed with respect to the interaction with receptor on B cells. The induction of B cell differentiation into Ig-secreting cells by B151-TRF was specifically inhibited by addition of N-acetyl-D-galactosamine (GalNAc) to culture. Such inhibition appeared to be attributed to the interference of GalNAc in the interaction of TRF with its receptor, because absorption of TRF activity with B cells was notably inhibited by the presence of GalNAc. To substantiate this point further, we established binding assay of B151-TRF molecule to the receptor on B cells by using 125I-labeled TRF fraction enriched by reversed-phase high-performance liquid chromatography and gel filtration. The results revealed that the binding of 125I-TRF molecule to the B cells was almost completely blocked by GalNAc. Moreover, the existence of GalNAc residue(s) on B151-TRF molecule was evidenced by the facts that 1) the TRF activity was eluted from lectin gels with specificity for GalNAc as revealed by the functional assay, and 2) the 125I-TRF molecule specifically bound to such lectin gels. Thus, the GalNAc residue(s) on B151-TRF molecule plays an important role in binding of TRF molecule to the receptor and in the stimulation of B cells. The molecular properties of B cell-stimulatory B151-TRF and its mode of interaction with corresponding receptor on B cells were discussed in the context of B151-TRF as a glycosylated lymphokine molecule and B151-TRF receptor as a carbohydrate-binding protein (animal lectin).
[Adaptation of dowel-retained cast cores].
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[Radiotherapy of pancreatic carcinoma].
During the 10-year period between 1974 and 1984, we treated 34 pancreatic carcinomas by radiotherapy as follows: Eight by intraoperative radiotherapy (IOR), five by external radiotherapy (ERT), and 21 by IOR in combination with ERT. The mean survival time of the eight patients treated by IOR was 5.6 months, and that of the 21 receiving the combination therapy 7.2 months. Although it is not statistically significant, patients treated by the combined regimen survived longer than those treated by IOR alone.
B cell growth and differentiation activity of a purified T cell-replacing factor (TRF) molecule from B151-T cell hybridoma.
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[Effects on the hard tissue of teeth in PCB poisoned rats].
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[Prevalence of periodontal disease in patients with yusho].
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Metabolic conversion of alpha-keto valine to valine in patients with chronic renal failure.
Change in the metabolic conversion rate of alpha-keto valine to valine following oral administration of the analog of the essential amino acid (0.1 g/kgB.W.) is studied in six patients with chronic renal failure and five control subjects under low protein, low and normal energy intake diets. Diet I is composed of 105 kj (25 kcal)/kgB.W. energy and 0.6 g/kgB.W. protein, whereas Diet II is composed of 165 kj (40 kcal)/kgB.W. with the same amount of protein intake. As a result, an increase in plasma keto valine concentration is observed immediately after oral administration, followed by an increase in plasma valine concentration, implying that metabolic conversion of alpha-keto valine to valine occurs within a small amount of time. In addition, the conversion rate appears to be accelerated under Diet II. It is therefore suggested that reutilization of urea nitrogen with the ketoanalog under the low protein diet seems to be promoted under adequate energy intake.
["Fibrinogen Kawaguchi": a hereditary dysfibrinogenemia characterized by defective release of fibrinopeptide A associated with altered polymerization of fibrin monomers].
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[Problems in the standardization of radiotherapy in cervical cancer].
In Japan there exists a interinstitutional difference in the response rate of cervical cancer, which is ascribed to the lack of intracavitary radiotherapy instruments. Provided the standardized treatment schedules are followed in all institutes, the over all responses will be definitely improved. Currently there are two major problems to be solved. Firstly, we have discussed IOR and hyperthermia to individualize locally advanced cervical cancers which are excluded from current standardized treatment method. Next we discussed indications for high dose rate intracavitary brachytherapy and the dose fractionation of it in relation to external beams.
[Clinical study of total cystectomy in patients with bladder transitional cell cancer].
The late results on 53 patients with bladder transitional cell cancer, who were treated by total cystectomy at the Department of Urology, Jichi Medical School between 1974 through 1983, were reviewed. The ages ranged from 28 to 78 years old, with an average of 61.8 years. There were 48 men and 5 women, with a male to female ratio of 9.6:1. The relative 5-year survival rate was 58.2% as a whole, that of patients with low grade cancer (grade 1 and 2) was 116%, and that of patients with high grade cancer (grade 3) was 33.8%. A significant difference was observed (p less than 0.01). The relative 3-year survival rate of low stage cancer (pT1 and pT2) was 88.4%, that of high stage cancer (pT3 and pT4) was 16.6%, a significant difference being observed (p less than 0.01). The post operative mortality rate was 5.7%.
[Studies on the production of anti-thyroglobulin autoantibody in vitro in patients with autoimmune thyroid diseases].
We have studied the production of anti-thyroglobulin autoantibody (ATA) in vitro in patients with autoimmune thyroid diseases to test the hypothesis that these patients have a deficiency in T suppressor cell function. Lymphocytes were cultured for 7 days with or without pokeweek mitogen (PWM). ATA and IgG concentrations in the culture supernatant were measured by enzyme immunoassays. In 15 patients with Hashimoto's disease (HD), ATA production in vitro was detected. These patients had very high titers of ATA in their sera. In 5 patients with HD who had low ATA titers in their sera, and in 20 normal individuals, ATA production was not detected. Therefore, ATA production in vitro was positively correlated with ATA concentration in the serum. The stimulating effect of PWM was not clear in ATA production, but apparent in IgG production. In another experiment, concanavalin A (Con A) was used to induce T suppressor cells, and the activities of these cells were detected in the PWM driven culture system of fresh lymphocytes. In 5 patients with HD, ATA production was inhibited by Con A induced autologous suppressor cells. And the degree of suppression in ATA production was the same as that seen in IgG production. Furthermore, in 2 patients we have compared the suppressing effect on ATA production of autologous Con A activated cells with that of normal Con A activated cells. There was no difference between the two. Therefore, we could not demonstrate the defect in Con A induced, non-specific suppressor cell activities in patients with HD. Finally, we cultured the lymphocytes with the specific antigen, Tg (10-100 micrograms/ml). The responses of ATA production to Tg were variable among patients, which may suggest the variety of the status of presensitized lymphocytes or antigen specific suppressor cells. Further studies are necessary to elucidate the antigen specific T cell function in autoimmune thyroid diseases.
[Abdominal angiography with a non-ionic contrast medium, iopamidol].
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Impaired monocyte differentiation in children with acute lymphoblastic leukaemia: its evaluation by peroxidase activity and ultrastructure.
The ability of monocyte differentiation in childhood acute lymphoblastic leukaemia (ALL) was evaluated on the basis of the ultrastructure and peroxidase (PO) activity which could show the differentiation of cultured monocytes. In the control, PO activity limited to the granules decreased time-dependently during culture for 4 d, and was closely associated with the morphological development to macrophages. In childhood ALL, monocytes showed poor changes in both PO activity and morphological features during culture for 4 d compared to the control. Therefore, we conclude that monocyte to macrophage differentiation is impaired in childhood ALL.
The occlusion of sodium ions within the mammalian sodium-potassium pump: its role in sodium transport.
The hypothesis that the ADP-sensitive form of phosphorylated Na+, K+-ATPase contains occluded sodium ions has been tested by a procedure which involves (i) modifying the enzyme with alpha-chymotrypsin or N-ethylmaleimide (NEM) so that the ADP-sensitive form is more stable than it is in the native enzyme, (ii) phosphorylating the modified enzyme with ATP in the presence of labelled sodium ions, and (iii) forcing the phosphorylated enzyme rapidly through a cation-exchange column and measuring the labelled sodium in the effluent. The results show that ADP-sensitive phosphoenzyme prepared from alpha-chymotrypsin- or NEM-modified Na+, K+-ATPase is able to carry labelled sodium ions through a cation-exchange resin. This behaviour was not seen with native Na+, K+-ATPase or when phosphorylation was prevented by the omission of magnesium ions or by the substitution of adenylyl(beta, gamma-methylene)diphosphonate (AMP-PCP) for ATP. The occluded sodium ions were rapidly released when the phosphoenzyme was dephosphorylated by ADP. When alpha-chymotrypsin-modified enzyme was phosphorylated by ATP with 1 mM-sodium in the medium, close to three sodium ions were occluded per phospho group. The stoicheiometry at much lower sodium concentrations could not be determined satisfactorily. A consideration of the rate constants of the reactions thought to be involved in the occlusion of sodium and in the release of sodium from the occluded state shows that, so far as they are known, these constants are compatible with the hypothesis that the occluded-sodium form of the phosphoenzyme plays a central role in sodium transport through the pump.
Substrate specificity of a thymidine phosphorylase in human liver tumor.
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