Biomedical subjects
Publications and source records attributed to T Miyazaki.
An allotypic G3m(g) marker-specific substitution was studied by sequence analysis of glycopeptides derived from myeloma proteins Ba (G3m(g+)) and Bu (G3m(g-)). The experimental results indicate that glutamic acid at position 295 is responsible for the specificity. Based on the results of chemical modification (Arg, Tyr, and Glu), this antigenic epitope is presumed to involve five sequential residues from Arg-292 to Tyr-296.
An intrasplenic injection (i.s.) of BALB/c bone marrow cells induces a higher survival rate than an intravenous injection (i.v.) in irradiated C3H/He recipients. Coculture experiments revealed the presence of alloantigen-specific and nonspecific suppressor cells in the spleens of mice injected i.s. and i.v. Suppressor activity decreased 50-60 days after bone marrow transplantation in i.v. chimeras, while there was no decrease in i.s. chimeras. In vitro suppressor activity was correlated with in vivo activity. Histopathological changes in the liver were examined. A total of 28% of the i.v. chimeras showed severe changes compared with 6% of the i.s. chimeras. The spleen indices of i.v. and i.s. chimeras were compared. Although there was no statistically significant difference between the spleen indices of i.v. chimeras and those of i.s. chimeras, spleen indices of i.v. chimeras tended to be higher than those of i.s. chimeras. These results show that suppressor cells in i.s. chimeras appear to inhibit graft-versus-host reactions more efficiently. Furthermore, an adoptive transfer assay showed that suppressor cells detected in i.s. chimeras were effective in vivo. We therefore suggest that suppressor cells detected in vitro correlate with in vivo activity and may play some role in the induction and maintenance of transplantation tolerance.
The producibility of interferon (IFN)-alpha, which indicates one of the functions of large granular lymphocytes (LGL), was impaired at a high frequency in myelodysplastic syndrome (MDS) patients. However, IFN-alpha production in refractory anaemia, which is a subtype of MDS, was almost normal. In contrast, abnormality has not been observed in either proliferative response or the production of IFN-gamma of T-cells by stimulation with PHA. NK activity of peripheral blood mononuclear cells (PBMC) from MDS patients was generally low and was not augmented by IFN-alpha treatment. These results indicate that, in addition to the abnormality at the level of haematopoietic tissues, LGL among PBMC may be impaired in MDS patients.
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A gene cluster encoding biphenyl- and chlorobiphenyl-degrading enzymes was cloned from a soil pseudomonad into Pseudomonas aeruginosa PAO1161. Chromosomal DNA from polychlorinated biphenyl-degrading Pseudomonas pseudoalcaligenes KF707 was digested with restriction endonuclease XhoI and cloned into the unique XhoI site of broad-host-range plasmid pKF330. Of 8,000 transformants tested, only 1, containing the chimeric plasmid pMFB1, rendered the host cell able to convert biphenyls and chlorobiphenyls to ring meta cleavage compounds via dihydrodiols and dihydroxy compounds. The chimeric plasmid contained a 7.9-kilobase XhoI insert. Subcloning experiments revealed that the genes bphA (encoding biphenyl dioxygenase), bphB (encoding dihydrodiol dehydrogenase), and bphC (encoding 2,3-dihydroxybiphenyl dioxygenase) were coded for by the 7.9-kilobase fragment. The gene order was bphA-bphB-bphC. The hydrolase activity, which converted the intermediate meta cleavage compounds to the final product, chlorobenzoic acids, and was encoded by a putative bphD gene, was missing from the cloned 7.9-kilobase fragment.
A father-child incompatibility only in the Gc system was detected in a paternity case tested at our laboratory. Quantitative determination revealed that the Gc level in the two individuals was less than 50% of the normal mean value. Evaluation of the probability calculation for the putative father using all other markers showed that he was the biological father with a very high probability. Thus it was concluded that a silent allele Gc*QO was transmitted from the father to the child.
We previously demonstrated that human embryonic mesenchymal cells derived from the palate (HEMP cells) retain alkaline phosphatase (ALP) content and capacity for collagen synthesis after long-term culture, and their growth is markedly stimulated by epidermal growth factor (EGF). There was a dramatic decrease in ALP content and capacity to synthesize collagen in HEMP cells (HEMP-RV cells) persistently infected with rubella virus (RV). EGF increased ALP activity and decreased collagen synthesis in HEMP cells, whereas EGF showed no effect on these activities in HEMP-RV cells. Growth of HEMP-RV cells was slightly reduced compared with that of HEMP cells. EGF stimulated growth of HEMP cells and to a lesser extent of HEMP-RV cells. Binding of 125I-EGF to cell-surface receptors in HEMP-RV cells was, to our surprise, twice as much as that in HEMP cells. However, internalization of bound 125I-EGF in HEMP-RV cells was profoundly diminished. Thus, persistent RV infection causes not only changes in HEMP cell growth and differentiation but a decrease in or loss of HEMP cell responsiveness to EGF. The effects of persistent RV infection on palatal cell differentiation as well as growth may be responsible for the pathogenesis of congenital rubella. Furthermore, since HEMP cells appear to be closely related to osteoblasts, these results suggest a mechanism for RV-induced osseous abnormalities manifested in congenital rubella patients.
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TSH receptor antibody (TRAb) activity using chicken thyroid receptor (c-TRAb) and porcine thyroid receptor (p-TRAb) was determined by the incubation of 125I-bovine TSH with each receptor. Both c-TRAb and p-TRAb activity in LATS positive and negative Graves' sera were compared. 15 out of 39 LATS positive sera and 4 out of 46 LATS negative sera had positive c-TRAb activity. On the other hand, all LATS positive sera and 33 out of 46 LATS negative sera had positive p-TRAb activity. No relationship between c-TRAb and p-TRAb activity was observed, and there was also no correlation between c-TRAb and LATS activity. Changes in c-TRAb, p-TRAb and LATS activity in the clinical course of patients with Graves' disease were examined. These activities were parallel in some cases, but in others they were not. A weak c-TRAb activity was observed in 4 out of 29 Hashimoto's disease, but all cases with thyroid cancer and subacute thyroiditis showed no activity. Sera with positive c-TRAb activity did not stimulate chicken thyroid in chick bioassay. These results suggest that some cases of TRAb in Graves' disease (mainly LATS) inhibit TSH binding to chicken thyroid receptor (non-mammalian species) in the same way as mammalian thyroid, but may not have any stimulatory action on thyroid hormone synthesis. It is interesting to note that TRAb including LATS have the similar effect on TSH receptor even in nonmammalian species.
The activities of the interferon-induced enzyme 2'-5' oligoadenylate synthetase in peripheral blood mononuclear cells were determined in patients with viral hepatitis. Increased levels of the enzyme were found in patients with acute type B hepatitis at the early phase and also in those with chronic type B hepatitis at the active stage. The levels of this enzyme activity were not significantly increased in patients with acute type A hepatitis or in those with acute type non A non B hepatitis. However, in two patients with acute type A hepatitis the levels of this enzyme were elevated shortly at the onset. These results support the hypothesis that an endogenous interferon response in patients with acute type A hepatitis and in those with acute type B hepatitis may be instrumental in the modulation of these types of hepatitis virus infections. Whereas hepatitis non A non B virus replication in patients with acute type non A non B hepatitis may be associated with poor interferon response. The activities of the enzyme in peripheral blood mononuclear cells were determined in patients with chronic type B hepatitis during interferon therapy. Increased levels of the enzyme were found in all patients during interferon therapy. This increase correlated well with the decreased DNA-polymerase activities. The data also showed that assay of this enzyme activity is useful to determine the optimal dosage and means of interferon therapy for chronic type B hepatitis.
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A clonal neoplastic epithelial duct cell (HSGc) of human salivary gland origin has a fine structure similar to the intercalated duct cell and the capacity to express secretory component and lactoferrin. HSGc cells tend to form an occasional glandular arrangement in vitro and in vivo, and transplantation of cells into nude mice resulted in production of adenocarcinoma. By repeated single cell cloning, different types of clones could be isolated from HSGc. Cuboidal clones resemble the parent cell, but fail to form the glandular arrangement or express lactoferrin, suggesting a less differentiated type. Elongated clones have a fine structure similar to myoepithelial cells and carry myoepithelial markers such as S100 protein, actin, and myosin which are not detected in the HSGc and its cuboidal clones. These myoepithelial-like clones are able to express secretory component, lactoferrin, and lysozyme and to produce glycosaminoglycans, suggesting that they are a functionally active form of the neoplastic cell but different from the normal myoepithelial cell. Judging from their growth properties in vitro and in vivo, the myoepithelial-like clones are less malignant than HSGc or its cuboidal clones. Of four elongated clones, two did not produce tumors in athymic mice, while all of the cuboidal clones were tumorigenic. These findings suggest a possible conversion of the neoplastic duct cell to myoepithelial-like variants with low malignancy.
Forty-one cases of embryonal carcinoma were analyzed from a clinico-pathological point of view. The clinical stages of the patients were: 21 cases in stage I, 8 in stage II, 11 in stage III and 1 in stage IV. Survival curves were compared in accordance with clinical stages. A statistically significant difference was demonstrated between stages I and III, and a significant difference was demonstrated between stages I and II. Embryonal carcinoma in a narrow sense and yolk sac carcinoma were compared in survival curve but there were no significant differences between the two. Cases were divided into two that were pure embryonal carcinoma and embryonal carcinoma with other constituent mixtures. A comparison of these two showed that the mixed type had a better survival curve than the pure type. Effects of treatment in two different periods were compared patients who were treated in 1971-1979 belong to the 1st period group and those treated in 1979-1985 to the 2nd period group. A comparison of these two showed a much better survival curve in the 2nd period group. This difference can be attributed partly to a VAC combination chemotherapy and its maintenance for two years and partly to improvements in the operating technique such as added omentectomy and or the introduction of a second look operation. By measuring alpha FP over the whole clinical course, alpha FP was shown to be a good tumor marker reflecting the patient's condition and aggravation of the patient's condition frequently occurred around or somewhat after 15 weeks after primary surgery.
As HLA studies suggest that the genetic factors contributing to the pathogenesis of Takayasu disease may be polygene, various red blood types, allotypes of serum protein and red blood cell enzyme polymorphisms in eighty-four patients with Takayasu disease were studied and their phenotypes and gene frequencies were compared with those in healthy Japanese. Statistically significant high frequencies of phenotypes and/or gene frequencies were confirmed in MNSs, Rh-Hr, Tf, Gc and Pi in Takayasu disease, as compared with those in controls. These characteristics of gene frequencies were more remarkable in patients who do not carry HLA Bw52. These data suggest that the genetic factors contributing to the pathogenesis of Takayasu disease are polygene and may be located in chromosome No. 1, 4 and 14.
We examined hematopoietic disorders in 74 patients with various malignancies. The proportions of patients with anemia in the case of esophageal carcinoma, gastric carcinoma, colorectal carcinoma, hepatoma, and pancreatic carcinoma were 75%, 87.5%, 77%, 64% and 87.5%, respectively. Hypochromic microcytic anemia was mainly observed in showed patients with carcinoma of the gastro-intestinal tract which showed severe bleeding. The major proportion of patients with hepatoma and pancreatic carcinoma showed normochromic normocytic anemia. The WBC count was usually within the normal range except for patients with liver cirrhosis or generalized metastasis who showed decreased WBC counts. The mean lymphocyte count in the peripheral blood, which is thought to be correlated with the prognosis of cancer patients, was less than 1,500/microliter except for patients with gastric carcinoma, whose five-year survival rate was 28.6%. Monocytosis was mainly observed in patients with colorectal carcinoma and pancreatic carcinoma, accounting for 24.5% of the total cases. This finding may suggest some relationship between cancer and monocytes. Thrombocytosis was seen in patients with severe bleeding, but thrombocytopenia was seen in patients with liver cirrhosis. Most cancer patients showed normo-cellular marrow and normal M/E. We also examined the ferrokinetics and ferritin levels in cancer patients.