[A case of sarcoidosis with a huge tumor of the anterior cervical region].
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Biomedical subjects
Publications and source records attributed to Y Kurata.
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A membrane antigen with an apparent specificity to B lymphocytes was detected with immunochemical techniques and its properties were analyzed. Anti-B-CLL serum was raised in a rabbit by immunization with B-cell chronic lymphocytic leukemia (B-CLL) cells. This anti-B-CLL serum was absorbed with erythrocytes, liver homogenate and insolubilized immunoglobulins. After further absorption with T-CLL cells, chronic myelocytic leukemia (CML) cells and acute myelocytic leukemia (AML) cells, the anti-B-CLL serum still reacted with peripheral blood B lymphocytes, B-CLL cells and hairy cell leukemia (HCL) cells. In contrast, no reactivity was seen with peripheral blood T lymphocyte or monocytes, or leukemia cells of non-B cell origin. An immunoprecipitation of radiolabeled cell surface proteins was attempted using the anti-B-CLL serum in the presence of Staphylococcus Aureus Cowan 1 (SaCl), and the precipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A membrane antigen with an apparent molecular weight of 76,000 daltons (P-76) was immunoprecipitated with the anti-B-CLL serum from the lysates of normal B lymphocyte, B-CLL cells and HCL cells. The antigen (P-76) is not composed of disulfide-linked subunits and has no structural relationship with HLA-DR (Ia-like) antigens or other known antigens. These results suggest that this antigen is B-lymphocyte specific, and favour the B-lymphocyte nature of HCL cells.
A case of "nonsecretory" myeloma is described. The patient had typical osteolytic lesions and marked infiltration of myeloma cells in the bone marrow, and plasma cell leukemia. A good partial remission was obtained with Melphalan, but the patient relapsed and died one year later. Immunofluorescent and immunoelectroscopic studies on the myeloma cells demonstrated the presence of cytoplasmic gamma-and kappa-chains at the initial stage and of only kappa-chains at a relapse. The electron microscopic method for polysome analysis indicated that both L-and H-chains were synthesized on membrane-bound polysomes initially, but the ability to produce H-chain was missing at the relapse.
Caramel colouring (ammonia process) was given at levels of 0 (control), 1.25 and 5.0% in the drinking-water to groups of 50 male and 50 female mice for 96 wk, and then all all the animals were maintained without caramel for a further 8 wk. Males given 5.0% caramel showed increased cumulative mortality from wk 100 to the end of the experiment. The white blood cell count in treated males was significantly elevated in a dose-related manner. However, these changes were not considered to be biologically significant. There were no treatment-related effects on clinical signs, body or organ weights, results of urine analyses, or histological features. Therefore, this study did not demonstrate any carcinogenic effect of caramel on mice at levels of up to 5.0% in the drinking-water.
The effects of timing of a single intragastric application of dibutyltin dichloride, at a dosage of 30 mg/kg body wt, on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas have been studied in female Syrian golden hamsters. Dibutyltin dichloride, which has been shown to produce selected bile duct injury, was administered either 1 week before or 1 week after a single injection of BOP (20 mg/kg body wt). Control hamsters were injected with BOP alone or were given dibutyltin dichloride alone. The incidence of ductal adenocarcinomas strikingly decreased in hamsters when dibutyltin dichloride was ingested after BOP treatment, but remained unaffected when dibutyltin dichloride was given before carcinogen treatment. Two cases of sarcoma were observed in the group treated with dibutyltin dichloride before BOP injection. The incidence of insulomas, which were considered as spontaneous tumors, was not influenced by dibutyltin dichloride. These results showed that intragastric application of dibutyltin dichloride after BOP treatment significantly reduced the induction of pancreatic cancer. These findings do not support speculations based on epidemiologic studies as to a promoting effect of cholestasis.
The structure and organization of a human repetitive DNA family containing the HindIII 1.8-kb repetitive sequence were studied, using two-dimensional (2D) gel electrophoresis. The HindIII 1.8-kb sequence proved to be part of a repetitive sequence about 5 kb long and interspersed on the genome. The long repetitive sequence family contained several subgroups, as based on polymorphism of the restriction site. Recombinant phages containing the long repetitive sequence were isolated from the human genomic DNA library. Heteroduplex and restriction analysis showed that the structure of the repetitive sequence carried by the phages was close to that expected from 2D gel electrophoretic analysis. The 2D gel electrophoretic analysis was shown to be a reliable and useful approach for surveying and mass analysis of repetitive sequence families.
In vitro phagocytosis of platelets from patients with idiopathic thrombocytopenic purpura (ITP) (direct assay) and phagocytosis of normal platelets sensitized with patient serum (indirect assay), using normal peripheral blood leukocytes, were studied to find out whether the degree of phagocytosis reflects the severity of ITP. Phagocytosis was measured by the uptake of 51Cr-labeled platelets. Among patients whose platelet count was below 10 X 10(4)/microliters, 92% showed an increase in the phagocytosis ratio by the direct assay and 67% by the indirect assay. There was a highly significant inverse correlation between the direct phagocytosis ratio and the platelet count (p less than 0.001), but not between the indirect phagocytosis ratio and the platelet count. The amount of platelet-associated IgG (PAIgG) measured in patients whose platelets were used for the direct assay also showed an inverse correlation with the platelet count (p less than 0.05). Vincristine administration provoked a reduction in the direct phagocytosis ratio and PAIgG value. We propose that both the direct assay and PAIgG measurement reflect the severity of ITP, and PAIgG might be responsible for platelet phagocytosis.
High-dose gammaglobulin therapy for patients with idiopathic thrombocytopenic purpura (ITP), introduced by Imbach et al., was applied to 5 adults with chronic refractory ITP to investigate the mechanism of the increase in platelet counts. In 4 of the 5 cases, transient increase in platelet count was observed. Platelet-associated IgG was decreased in 3 cases, increased in 1 case and unchanged in 1 case after treatment. In 4 cases having a variety of autoantibodies, the antibody titers decreased after treatment. No significant changes in antiplatelet antibody titers in serum, or in circulating immune complexes were observed during or after these treatments. No side effects were noted in any of the cases. These results indicate that the treatment is suitable for the treatment of patients prior to surgery and of patients at high risk of intense bleeding and death. It can be reasonably assumed that the increased platelet count is mainly due to a defective removal of antibody-coated platelets.
T cell subsets of peripheral lymphocytes were studied using monoclonal antibodies (OKT3, OKT4, OKT8) and immunoglobulin (IgG, IgM, IgA) synthesis in vitro by peripheral mononuclear cells stimulated with pokeweed mitogen was studied in adult patients with idiopathic thrombocytopenic purpura before and after high-dose intravenous intact gamma(gamma-)globulin therapy, at a daily dose of 0.4g/kg body weight for 5 consecutive days. A transient increase in platelet count which reached a peak on the 1st to 2nd days after the end of the therapy was observed in four of five patients. Immunoglobulin synthesis in vitro was suppressed remarkably following therapy in all cases: the mean reduction of IgG, IgM and IgA was 78, 66 and 48%, respectively. Titres of various autoantibodies, TGHA, MCHA, ANF and anti-DNA antibody, also decreased following therapy. In correspondence to this, phenotypic analysis in T cell subsets showed a decrease of OKT4+:OKT8+ ratio following therapy, without a change in the proportion of OKT3+ cells. These data indicate that the intravenous gamma-globulin preparations suppressed synthesis of antibodies non-specifically and caused a relative increase of OKT8+ suppressor T cells.
Four groups of 21 male Wistar rats were given weekly subcutaneous injections of 1,2-dimethylhydrazine at a dose of 20 mg/kg body weight for 2, 4, 6 and 8 weeks, respectively, and 7 animals of each group were killed in weeks 24, 32 and 40. This treatment induced a clear dose-related increase in the total number of colonic carcinomas. The number of tubular adenocarcinomas, which were mostly located in the descending colon, was clearly dose-related, whereas the number of signet ring cell carcinomas, which developed in the ascending colon, was apparently dose-independent.
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The effects of sodium o-phenylphenate (OPP-Na) and o-phenylphenol (OPP) on 2-stage urinary bladder carcinogenesis in F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at levels of 0.01 or 0.05% in drinking water were investigated. Administration of 2.0% OPP-Na in the diet significantly increased both the incidence and the number per 10 cm of basement membrane of preneoplastic lesions (papillary or nodular hyperplasia; PN hyperplasia) of the urinary bladder in rats pretreated with 0.01% BBN, and also those of papilloma and cancer of the urinary bladder in the group pretreated with 0.05% BBN. Moreover, treatment with 2.0% OPP-Na, without prior BBN initiation, induced PN hyperplasia, papilloma and cancer. In contrast, OPP appeared to produce only a slight increase in the incidence of urinary bladder lesions following BBN, and its effect was not statistically significant. It also did not induce tumors of the urinary bladder. These results provide evidence that OPP-Na has promoting activity toward the urinary bladder while OPP does not. Moreover, the possibility that OPP-Na may be a complete carcinogen in the rat urinary bladder deserves consideration.
To determine the pathomechanism of the condition of CF 1 mutant mice which present paralytic club feet, anatomicohistological analysis (conventional histological staining, silver impregnation, cholinesterase staining, and retrograde tracer technique of horseradish peroxidase (HRP)) were carried out. CF 1 homozygotic mutant mice lacked the common peroneal nerve, while tibial nerve is larger than that of normal mice when they were compared at the similar levels of the posterior limbs. Anterior and lateral crural muscles of the homozygotic mutant mice except for peroneus longus and brevis muscles showed large group muscle atrophy. HRP study indicated that the number of HRP labeled cells after injection of HRP into the anterior and lateral crural muscles decreased remarkably in number in the homozygotic mutant mice, comparing with that of the normal mice.
Tumor-promoting effects of phenobarbital (PB) and sodium saccharin (SS) were tested in rats pretreated with N-nitrosomethylurea (NMU) with special reference to the site of their action. Male F344 rats were initially given injections of NMU (20 mg/kg i.p.) twice a week for 4 weeks, then given basal diet containing 0.05% PB or 5% SS for the next 32 weeks, and then killed. Appropriate control studies were also done. Histological examination of whole organs of the rats showed that PB promoted thyroid carcinogenesis whereas SS did not. A significant increase in the incidences of total tumors as well as papillary adenocarcinoma of the thyroid was observed in the group given PB after NMU (p less than 0.001). The incidence of papillary adenoma with or without papillary adenocarcinomas was also high in the NMU-PB-treated group. The organ-specific promoting effect of PB in the induction of preneoplastic lesions, as demonstrated by development of gamma-glutamyl transpeptidase-positive foci in the liver and of SS in papillary or nodular hyperplasia in the urinary bladder, as reported previously, was also confirmed. The incidences of papillomas in the forestomach were similar in groups treated with NMU-PB, NMU-SS, or NMU alone. The results indicate that PB is a tumor promoter in the liver and thyroid and that SS is a tumor promoter in the urinary bladder of rats.
Groups of 52 B6C3F1 mice of each sex were maintained on a diet containing 1.25 or 0.6% phenacetin for 96 weeks and then fed a basal diet for 8 weeks. Control groups consisted of 50 mice of each sex and were fed a basal diet for 104 weeks. All animals were killed at the end of the experiment and all organs were examined histopathologically. Mice that died during the experiment were also autopsied and those that survived for more than 57 weeks, when the first tumor was observed, were also included in the effective number of mice. Tumors were found in the kidney, liver, lung, skin, hematopoietic system (leukemia or lymphoma) and occasionally in some other organs. The dose-related induction of renal cell tumors in the male mice fed phenacetin was clearly demonstrated in this experiment. Urinary bladder lesions that developed in the mice of either sex fed 1.25% phenacetin were also considered to be due to the tumorigenicity of phenacetin. Tumors of other organs in either the phenacetin-treated or the control group were regarded as strain-related spontaneous tumors of B6C3F1 mice.
To clarify the neural and humoral factors which control gastric receptive relaxation, the effects of various types of vagotomy or splanchnicotomy on receptive relaxation of the canine innervated corpus pouch were investigated. The influence of gastrin, histamine H1-receptor antagonist, and anti-histamine releasing agents on receptive relaxation were also examined. Selective proximal vagotomy or splanchnicotomy resulted in a slight disturbance in receptive relaxation. Truncal vagotomy produced a marked disturbance in receptive relaxation. Administration of tetragastrin potently inhibited receptive relaxation, however, recovery occurred by injecting a histamine H1-receptor antagonist. Increased serum gastrin induced by perfusion of the antrum with liver extract solution disturbed receptive relaxation and this response was inhibited by pretreatment with transamine, an inhibitor of histamine release from histamine secreting cells. These results indicate that receptive relaxation in the canine stomach is controlled not only by vagal and splanchnic nerves, but also by gastrin and histamine.
Groups of approximately 50 male and 50 female B6C3F1 mice were given butylated hydroxytoluene (BHT) at concentrations of 200, 1000 or 5000 ppm in their diet for 96 wk followed by a basal diet for 8 wk and were then killed. Similar groups of male and female controls were given basal diet throughout the 104 wk. Females given 1000 or 5000 ppm BHT and males given 5000 ppm showed reduced weight gain. Neither survival rates nor food consumption differed between experimental and control groups. No significant changes attributable to BHT treatment were found in the haematological examinations or serum and urine analyses. Tumours were found in many organs, especially the lungs, liver, lymph nodes and spleen, in both the experimental and control groups, but none were related to BHT treatment. Thus this experiment provided no evidence of BHT carcinogenicity in mice.
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