Biomedical subjects
Publications and source records attributed to K Kakimoto.
A 46-year-old female underwent an excision of a parathyroid adenoma diagnosed as recurrent primary hyperparathyroidism 24 years after the initial excision of a parathyroid adenoma. We report a case of non-synchronous double adenomas of the parathyroid glands documented histopathologically.
We evaluated the effect of impression materials used in preparation of pure titanium castings on the surface reactive layer. Surface roughness of the refractory models before and after firing was smaller when silicone rather than agar impression material was used. The surface roughness of castings prepared with T-invest varied little with the impression material. However, the surface roughness of the castings prepared with CD Titaninvest was less when silicone impression material was used. Surface hardness of the castings was slightly greater when agar impression material was used, and metallic texture analysis of the surface of the castings showed a chill layer and a columnar crystal layer extending from the surface toward the interior. A relatively non-corroded white layer and a markedly corroded black layer were observed in the chill layer, and their thickness was smaller when silicone impression material was used. Use of the Electron Probe Micro Analyzer (EPMA) to determine distribution of various elements in the superficial layer of the casting plates showed that the reactive layer contained less P and Si when silicone impression material was used rather than agar. NH4H2 PO4, which is a component of the bonding material in the investment, was present at a high concentration in the superficial layer of the agar impression material. This shows the importance of preparing refractory models with a non-water-absorbing impression material to obtain pure titanium casting plates with a smaller reactive layer.
It has been proposed that superantigens are involved in the pathogenesis of autoimmune diseases. To test the possibility of superantigens inducing arthritis in naive mice, V beta 8-reactive superantigen staphylococcal enterotoxin B (SEB) was injected into naive mice. We used female DBA/1 mice, because they were susceptible to collagen-induced arthritis (CIA), in which the pathogenic T cells were supposed to preferentially use limited V betas of T cell receptors including V beta 8. Mild monoarthritis developed in uninjected hindlimbs of mice administered with SEB in higher frequency (an average incidence of 24%) than the control phosphate-buffered saline-injected mice (4.2%). Autoimmune responses in mice administered with SEB were compared with those in mice developing CIA. However, activation of type II collagen (IIC)-reactive T cells was not detected in SEB-injected mice. Production of autoantibodies, anti-IIC antibody and rheumatoid factor was also undetected. Although exact mechanisms of pathogenesis of this arthritis remain to be known, V beta 8+ T cells were activated for a long period and the unresponsiveness of V beta 8+ T cells was not detected in this strain. From these results, we discuss the pathogenesis of arthritis induced by SEB and the possibility that superantigen may play a role in the induction of autoimmune diseases.
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The mutagenicity of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was investigated by the reverse mutation test in bacteria, the chromosome aberration test in vitro, and the micronucleus test in mice. The reverse mutation test was performed at a dose from 31.3 to 4000 micrograms/plate, at which dose cell killing was observed, using Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA. NS-21 did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S9 mix). The chromosome aberration test was carried out at a dose from 3.75 to 140 micrograms/ml, at which dose more than 50% cell proliferation was inhibited, using cultured Chinese hamster lung cells (CHL/IU). No significant increases of the frequencies of cells with chromosome aberrations were observed with or without S9 mix. The micronucleus test was conducted in the bone marrow cells of Slc : ddY male mice. Mice were given NS-21 by a single oral administration at doses of 0, 43.8, 87.5, 175, and 350 mg/kg, the geometric mean dose between the maximum tolerated dose and the minimum lethal dose. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes at any dose levels. These results show that NS-21 has no mutagenic activity in vitro or in vivo.
We report a case of renal cell carcinoma in acquired cystic disease of the kidney (ACDK) presenting with a spontaneous renal rupture. A 41-year-old man on chronic hemodialysis for 16 years was referred to our hospital with sudden left back pain. On arrival, the patient was in a state of hemorrhagic shock but his general condition improved by conservative therapy. Computed tomography demonstrated a left renal rupture as well as bilateral ACDK. Although there was no definite evidence of a renal tumor, a left radical nephrectomy was performed one week later. The resected kidney contained a yellowish-brown tumor of 5.5 x 5.0 x 4.5 cm in size. Pathological examination revealed renal cell carcinoma, cystic type, clear cell subtype, pT2pN0M0. He has been free of recurrence for 3 months.
T cell vaccination, originally contrived and coinned by I.R. Cohen is the injection of autoimmune pathogenic T cell line/clone or T cell receptor peptides in an attempt to induce anti-idiotypic regulation to treat autoimmune disease. Establishment of many T cell lines/clones from various autoimmune animal model and successful injection of these cells as T cell vaccine have been reported, although the exact mechanism for vaccination effect has not been elucidated. However, recent reports suggest that not the clonal deletion or anergy but the shift of Th1/Th2 balance of disease-related T lymphocytes may be involved in the effect of vaccination.
The pathogenesis of lung complications in autoimmune disease remains unclear. To examine whether superantigens participate in the development of interstitial pneumonia in autoimmune disease, we instilled the bacterial superantigen staphylococcal enterotoxin B (SEB) into the tracheas of autoimmune and nonautoimmune mice. The intratracheal administration of SEB resulted in the induction of interstitial pneumonia manifested by infiltration of mononuclear cells into the alveolar septal walls and into the periarterial space and an increase in pulmonary interstitial collagen fibers in the autoimmune mouse strains. In the nonautoimmune strains, AKR, but not BALB/c and B10BR, mice also developed interstitial pneumonia after the intratracheal administration of SEB, although the degree of severity was milder than that induced in three autoimmune mouse strains. Although the intratracheal administration of another bacterial superantigen staphylococcal enterotoxin A also induced interstitial pneumonia, protein A which is a staphylococcal product but not a superantigen induced no remarkable change in lungs of MRL-+/+ mice. Immunohistologic studies revealed that not only SEB-reactive Vbeta8+ T cells, but also SEB-nonreactive Vbeta6+ T cells infiltrated the pulmonary lesions of SEB-primed MRL-+/+ mice, although this may be a secondary reaction for the Vbeta6+ T cells. The results of in vitro restimulation of spleen cells from SEB-primed BALB/c and SEB-primed MRL-+/+ mice with SEB suggest that incomplete induction of tolerance after the intratracheal administration of SEB may be involved in the pathogenesis of interstitial pneumonia induced in autoimmune mice. These results suggest participation of superantigens in the development of interstitial pneumonia in patients with autoimmune disease and other lung diseases such as idiopathic pulmonary fibrosis.
In order to investigate the role of pathogenic T cells in RA, the establishment of an RA model using patients' T cells is thought to be essential. In this study, multiple and severe destructive arthritis was established by transferring in vitro-stimulated synovial fluid T (SFT) cells from patients with RA through simultaneous injection into knee joint and peritoneal cavity of SCID mice without causing xenogeneic graft-versus-host disease (GVHD). Neither the transfer of unstimulated SFT cells nor sole i.p. injection was sufficient to induce severe arthritis. Interestingly, in contrast with SFT cells, in vitro-activated peripheral blood lymphocytes from RA patients failed to trigger such arthritis, suggesting that pathogenic T cells might be concentrated in synovial fluid of RA patients. This, the first severe arthritis model mimicking RA induced by RA patients' T cells, is expected to provide important information about RA pathogenesis and a possible therapeutic approach.
An understanding of the intracellular relation between hormonal expression (storage) and gene expression (production) is essential for elucidating the functional status of the individual cells in endocrine tissue such as the pituitary gland. To this end, mRNA expression was visualised by using a combined in situ hybridisation and immunohistochemistry method in routinely processed, formalin fixed, paraffin wax embedded rat pituitaries. mRNA was detected by non-isotopic in situ hybridisation (alkaline phosphatase antialkaline phosphatase method, with nitroblue tetrazolium and 5-bromo-4-chloro-3-indolylphosphate as substrates). Sections were then stained by using the immunoperoxidase method to demonstrate pituitary hormone expression. The specificity of the combined staining method was confirmed by staining adjacent sections separately. The antigenicity of rat growth hormone and prolactin was adequately preserved following hybridisation. In conclusion, this method is specific, easy to use and permits the determination of the functional status of individual cells.
We reviewed 45 cases of transitional cell carcinoma of the renal pelvis and ureter with reference to the coexistence or subsequent development of bladder cancer. Bladder cancer was associated with an upper urinary tract neoplasm in 26 of the 45 cases. The 5-year survival rate for coexistence of bladder cancer was 56% and that for subsequent bladder cancer was 65.6%. The 5-year survival rate for 19 cases unrelated with bladder cancer was 46.7%. Therefore, there was no significant difference among the three groups. As to degree of the malignancy of the renal pelvis and ureter, the 5-year survival rate was 73.7% for G1 and G2 and 26.2% for G3. As to the depth of invasion, of the renal pelvis and ureter the 5-year survival rate was 71.8% and 31.1% in the patients with stage of T1, T2 and T3, T4. The prognosis of cancer of the upper urinary tract depended on the degree of the malignancy, and the depth of invasion. Ninety two percent of subsequent bladder cancer was detected within 2 years after resection of the primary cancer.
Endometrial stromal sarcoma (ESS) is a rare uterine malignancy. We describe a case of an ESS recurrence arising near a stump after hysterectomy. The 47-year-old patient had the operation at another hospital because of myoma uteri as a preoperative diagnosis. Since the postoperative pathological diagnosis was ESS, CYVADIC was administered as adjuvant chemotherapy. But 3 years later, an isolated recurrent tumor was found locally near a stump in the pelvis. The patient underwent a combination of an intra-arterial chemotherapy and radiotherapy. Cisplatin and Adriamycin was administered in 20 mg/m2 everyday for 5 days and 60 mg for 1 day, respectively. On the other hand, the tumor irradiation dose was 50 Gy for 5 weeks. After this combination therapy, the recurrent tumor size grew smaller on CT. This result suggests that the combination of intra-arterial administration of cisplatin and Adriamycin, and radiation is an effective therapy for a localized recurrent tumor of ESS.
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A novel neutrophil elastase inhibitor, ONO-5046, was administered to BB/DR rats and DBA/1 mice immunized with type II collagen to study its effect on the development of collagen-induced arthritis (CA), an experimental model of human rheumatoid arthritis. ONO-5046 reduced the incidence as well as the severity of CA in both rats and mice. This suppressive effect on severity was correlated with improvement of the histological findings, particularly with reduced destruction of the articular cartilage. These results indicate that neutrophil elastase may play an important role in the pathogenesis of CA.
We recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T cell leukemia virus type 1 genome. In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated. Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular immune response to IIC as well as that to heat shock proteins were activated. Moreover, these mice became immunologically responsive to exogenously administered IIC and developed arthritis, in contrast to their nontransgenic littermates, which showed little response to IIC. Taken together, the results suggest that human T cell leukemia virus type 1 can cause immune system hyperreactivity and induce autoimmunity. The possibility that elevated cytokine and/or MHC gene expression are involved in the development of autoimmunity and arthropathy are discussed.
An acute type rejection episode occurred in one of two patients treated with Interferon alpha (IFN alpha) for type C hepatitis (CHC). Histopathological examination of the graft kidney revealed focal cellular infiltration and chronic transplant glomerulopathy which showed acute or chronic type rejection. In spite of bolus administration of methyl-prednisolone, the elevation of serum creatinine level continued. After administration of anti-human lymphocyte globulin (AHLG), renal function improved, but urinary protein was still positive. Another patient had no episode of rejection during or after IFN alpha therapy.
A series of metal chlorides were subjected to the wing spot test of Drosophila melanogaster. In the test, larvae trans-heterozygous for the wing-hair mutations mwh and flr were orally treated at the third instar stage with a test compound and the wings were inspected at the adult stage for spots expressing phenotypes of the markers. CoCl2, MnCl2, MoCl3, NiCl2 and ZnCl2 were clearly effective in inducing spots with one or two mutant hairs (small spots). CoCl2 was clearly effective in inducing spots with three or more mutant hairs (large spots) as well. CrCl3, FeCl2 and FeCl3 were negative under the conditions used. Based on estimated frequencies of small spots induced at the LD50, the genotoxic effectiveness of the positive metal salts were ranked in a sequence of CoCl2 > ZnCl2 > MoCl3 > (MnCl2, NiCl2). Since CoCl2 did not induce large spots in the wings of the mwh/TM3 flies with a suppressed ability of mitotic crossing-over, the large spots induced by this compound in the mwh/flr system were ascertained as mutant clones due to mitotic crossing-overs.
We report a case of renal allograft rejection induced by the administration of interferon-alpha for hepatitis type C in a 36-year-old male. In September 1986, renal transplantation from his brother was performed after a 6-month delay because of his liver dysfunction. In October 1992, under the diagnosis of chronic active hepatitis type C, interferon alpha therapy was administered. Although his liver function was normalized during the treatment, proteinuria turned positive after 8 weeks of the therapy. Fourteen weeks after the start of interferon alpha therapy, the serum creatinine level was elevated, which was diagnosed clinically as a rejection reaction. We first discontinued the medication of interferon alpha and administered steroid pulse injection. As the renal disfunction did not respond to our first treatment, we changed mizoribine to azathioprine and added horse antilymphocyte immunoglobulin. Two weeks later, the creatinine level improved from 2.5 mg/dl to 2.0 mg/dl. The pathological findings of the transplanted kidney were acute on chronic type rejection.