[Statistical study on tumors of the urinary bladder--clinico-pathological determinants of prognostic significance].
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Adult↗
Biomedical subjects
H Mitsuya
Publications and source records attributed to H Mitsuya.
Implications of the discovery of HTLV-III for the treatment of AIDS.
The recent discovery of HTLV-III, a cytopathic member of the family of human T-cell lymphotropic viruses (HTLV), and its identification as the etiological agent of acquired immunodeficiency syndrome (AIDS) have important implications for the treatment of this disorder. The pathogenesis of AIDS involves the destruction of helper/inducer T-lymphocytes by active viral infection, and drugs which inhibit the replication of HTLV-III or monoclonal antibodies directed at viral antigens may be important components of future therapeutic strategies. There are a number of steps in the replication of HTLV-III which might potentially be susceptible to antiviral agents. One drug, suramin, which was originally developed as an antitrypanosomal agent, has been found to be an inhibitor of reverse transcriptase. This drug has been shown to block the infectivity and cytopathic effect of HTLV-III [Mitsuya, H., Popovic, M., Yarchoan, R., Matsushita, S., Gallo, R. C., and Broder, S. Science (Wash. DC), 266: 172-174, 1984]; in addition, it is able to block the in vitro replication of another member of the HTLV family, HTLV-I, at concentrations of 25 to 75 micrograms/ml. Lymphocyte proliferation in vitro is minimally inhibited at these concentrations of suramin, and the ratios of helper/inducer to cytotoxic/suppressor T-lymphocytes are not affected. Clinical trials are being initiated to study the effect of suramin on patients with AIDS. Evaluation of this and other antiviral treatments for AIDS will optimally involve direct assessment of its effects on HTLV-III replication in vivo. Recent evidence, however, suggests that these patients have a low level of viral replication in lymphoid tissue which may spontaneously fluctuate, making such evaluation complex.
Acquired Immunodeficiency Syndrome↗
[A case of primary adenocarcinoma of the urinary bladder occurring in a patient with type 1 multiple endocrine adenomatosis (MEA)].
A case of primary adenocarcinoma of the urinary bladder occurring in a patient with type 1 multiple endocrine adenomatosis (MEA) is presented. The patient was a 36-year-old female who had a past history of type 1 multiple endocrine adenomatosis, namely, adenomatosis of the parathyroid gland, insulin and gastrin-producing adenomatosis of the pancreas, and prolactin-producing pituitary adenoma. She was admitted in January 1981 with the complaints of gross hematuria, pollakisuria and micturition pain lasting for about one year and a half. Cystoscopic examination revealed four solid tumors in the posterior and left lateral walls of the bladder with diffuse mucosal hyperemia. Biopsy of the tumors disclosed that they were adenocarcinoma. Clinical examinations revealed that there was no extravesical primary malignant neoplasm in this case. Radical cystectomy with urinary diversion by ileal conduit was performed on January 22, 1981. Histological examination revealed that the tumor was adenocarcinoma originating from the vesical mucosa. Follow-up for over three years since the time of surgery has not shown any sign of tumor recurrence or occurrence of extravesical malignant neoplasm. In addition, 28 cases of primary adenocarcinoma of urinary bladder in Japan reported during the last 25 years are reviewed and analyzed.
Adenocarcinoma↗
Pharmacological inhibition of infectivity of HTLV-III in vitro.
Acquired immunodeficiency syndrome (AIDS) is a pandemic immunosuppressive disease that predisposes to life-threatening opportunistic infections and unusual forms of neoplasms. A recently discovered member of the human T-lymphotrophic virus (HTLV) family, designated HTLV-III, has been shown to be the etiological agent of AIDS. We have shown previously that a trypanosomicidal drug, suramin, can block the in vitro infectivity and cytopathic effect of HTLV-III at doses that are attainable in human beings. In the present work we report our findings that suramin can block the cytopathic effect of HTLV-III even after a defined exposure of the target helper/inducer T-cells to the virus and that the T-cells protected by suramin remain immunologically functional.
B-Lymphocytes↗
[Effect of etoposide for urogenital tumors].
Ten patients with urogenital tumors were treated with Etoposide. The dose schedule was 100 mg i.v. daily for 5 days and was repeated after 4-5 weeks. One patient with ureteral tumor experienced partial remission for 60 days and minor regression was achieved in 3 patients. The major side effects were leukopenia (60%) and thrombocytopenia (40%). Mean WBC nadir of 1050/mm3 occurred at 13.5 days and recovered quickly after a further 7.5 days.
Adenocarcinoma↗
[Total cystectomy for urinary bladder cancer: clinicopathological study of 95 cases].
Total cystectomy was performed on 95 patients with primary urinary bladder cancer between 1973 and 1983. Histopathological and prognostic studies were reviewed according to the general rules for clinical and pathological studies on bladder cancer. The cancer histological type were transitional cell carcinoma in 87 cases, squamous cell carcinoma in 5 cases, adenocarcinoma in 2 cases, and undifferentiated carcinoma in 1 case. The overall 5-year actuarial survival rate was 36.0%. As for the growth pattern of the bladder cancer, the 5-year survival rates for the patients with papillary non-invasive type (PNT), papillary invasive type (PIT), and non-papillary invasive type (NIT) were 100%, 25.8% and 34.8% respectively. As for the stage, the 5-year survival rates for the patients with pTa, pT1, pT2, pT3a, pT3b, and pT4 were 81.8%, 64.7%, 40.1%, 30.5%, 22.6% and 6.7% respectively. Of 87 patients with transitional cell carcinoma, the 5-year survival rates for the patients with grade 1, grade 2 and grade 3 were 100%, 43.0% and 32.1% respectively. Intramural lymphatic invasion and vascular invasion and intramural histopathological mode of spread were significant indicators of prognosis.
Adenocarcinoma↗
[A case of renal oncocytoma].
A case of renal oncocytoma is reported. A 56-year-old woman was admitted with the complaint of an abdominal mass. Right transabdominal nephrectomy was performed on January 23, 1984. The resected kidney weighed 262 g and contained a well-demarcated 5 X 5 X 4 cm tumor in the middle portion. The cross section of the tumor was tan-brown. Light microscopic examination disclosed that the greater part of the tumor was composed of cells with abundant, and finely granular eosinophilic cytoplasm and with moderate nuclear pleomorphism. Electron microscopic examination confirmed that the cytoplasm had numerous mitochondria and few other organelles. According to these findings, the tumor was diagnosed as renal oncocytoma. Furthermore, it is noteworthy that in this case there were tubular arrangement of the cells resembling proximal renal tubules in a focal area and a group of cells with considerable nuclear atypia and hyperchromatism in another area. The patient has been well without any local recurrence or distant metastasis ten months after the operation. In addition, fourteen cases of renal oncocytoma in Japan, including the present case, are reviewed.
Adenoma↗
[Nine cases of bladder cancer occurring in occupational dye users].
Workers in the dye manufacturing industry have a high risk of urinary bladder cancer. There may also be a high relative risk of bladder cancer in occupational dye users. Nine occupational dye users were found to have bladder cancer. The period of engaging with dye work ranged from 5 to 40 years. Seven patients had bladder cancer and the other 2 patients had lesions both in the bladder and in the renal pelvis. Histopathology of all cases was transitional cell carcinoma. Three cases were classified into grade 1 and 6 cases into grade 2. One patient died of bladder cancer. The other 8 patients are alive. Four cases recurred after TUR therapy. It is necessary to establish systemic mass screening examination of occupational dye users for the early diagnosis of bladder cancer.
Aged↗
Abnormal urinalysis in acute appendicitis.
In a retrospective review of 32 consecutive patients (20 adults and 12 children) with acute appendicitis, we correlated abnormal urinalysis with the operative findings. Abnormal results on urinalysis were noted in 10 adults and 5 children. All urine specimens were collected by the clean-catch method. Abnormal findings were found more frequently in female patients. The majority of the patients with abnormal urinalysis had a ruptured or inflamed appendix in proximity to the urinary tract.
Acute Disease↗
Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III.
A recently discovered member of the human T-cell leukemia virus (HTLV) family of retroviruses has been etiologically linked to the acquired immune deficiency syndrome (AIDS). This virus, which has been designated HTLV-III, is tropic for OKT4-bearing (helper-inducer) T cells. Moreover, the virus is cytopathic for these cells. Suramin is a drug used in the therapy of Rhodesian trypanosomiasis and onchocerciasis, and it is known to inhibit the reverse transcriptase of a number of retroviruses. Suramin has now been found to block in vitro the infectivity and cytopathic effect of HTLV-III at doses that are clinically attainable in human beings.
Cell Line↗
Functional properties of antigen-specific T cells infected by human T-cell leukemia-lymphoma virus (HTLV-I).
Tetanus-toxoid specific helper-inducer T-cell clones, which had been infected and transformed by human T-cell leukemia-lymphoma virus (HTLV-I), were obtained from an antigen-specific human T cell line by using a limiting dilution technique in the presence of the virus. These HTLV-I-infected T-cell clones proliferated specifically in response to soluble tetanus toxoid but, unlike normal T cells, they could do so in the absence of accessory cells. The HTLV-I-infected T-cell clones did not present the antigen to autologous antigen-specific T cells that were not infected with HTLV-I. The capacity of helper-inducer T cells to retain antigen-specific reactivity after infection by HTLV-I, while losing the normal T-cell requirement for accessory cells, has clinical and theoretical implications.
Antigens, Surface↗
Massive IgE-hyperimmunoglobulinemia and storage histiocytosis in Sézary syndrome. A postmortem study.
Substantial evidence has accumulated that the Sézary syndrome is grouped together as "cutaneous T-cell lymphoma" and forms a subset of T-cells programmed for helper interactions with B-cells in their production of immunoglobulins; IgA, IgG, and IgM. The authors describe an autopsy case of a 64-year-old Japanese man, with cutaneous T-cell lymphoma in association with IgE-type lambda hyperimmunoglobulinemia. The serologic and immunocytochemical studies suggest that Sézary cells from our patient are T-cell proliferations in association with IgE-specific helper activity. In addition, histiocytosis was interestingly noted, for the first time, in the generalized lymph nodes, spleen, and bone marrow by the autopsy. The cytoplasm of swelled histiocytes contained IgE-type lambda immunoglobulin by the PAP method that probably represented altered immunoglobulin.
Cell Division↗
Immunologic studies of peripheral blood in a child with hypogammaglobulinemia. Suggested mechanism for the development of malignant B-cell lymphoma.
A case of a 7-year-old boy with common variable hypogammaglobulinemia who developed B-cell-type non-Hodgkin's lymphoma is reported. Immunologic studies of his peripheral blood before the development of lymphoma revealed: (1) although peripheral T-cell and B-cell counts were normal, serum IgG and IgA levels were remarkably reduced; (2) DNA synthesis in response to phytohemagglutinin-P (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) stimulation were decreased; (3) DNA synthesis in response to EBV was enhanced; (4) in vitro IgG production with the patient's peripheral blood lymphocytes was significantly depressed; and (5) helper and suppressor activities of the patient's T-cells did not differ from that of normal controls. Six months after the investigation systemic involvement of malignant lymphoma appeared. The lymphoma was diagnosed as a lymphoblastic diffuse one. Lymph node cell marker analysis revealed that the lymphoblasts had surface mu and kappa chain, cytoplasmic IgM, and HLA-DR antigen. Blastogenesis of B-cell series may be suppressed by a feedback mechanism with the B-cells and antibody. In the current case, impairment of such a mechanism with defect of immunoglobulin production might finally induce malignant B-lymphoid proliferation.
Agammaglobulinemia↗
Immune T cells reactive against human T-cell leukaemia/lymphoma virus.
Six patients with malignant disorders associated with human T-cell leukaemia/lymphoma virus (HTLV) were studied to see whether long-term cultures of immune T cells reactive against HTLV-infected tumour cells could be achieved. Immune T-cell lines could not be developed from the cells of five patients who died or eventually had a relapse of disease, but in one patient who had an unusually long remission of his disease after therapy, immune T-cell lines were propagated that could produce their own T-cell growth factor and proliferate upon stimulation with autologous tumour cells and also specifically lyse HTLV-infected target cells. These immune T cells recognised the presence of circulating HTLV-bearing neoplastic cells in another patient with HTLV-associated T-cell leukaemia, who had been in clinical remission after chemotherapy when this study started, thereby providing early evidence of relapse.
Cell Line↗
Transformation and cytopathogenic effect in an immune human T-cell clone infected by HTLV-I.
Human T-cell leukemia-lymphoma virus (HTLV) is a human C-type retrovirus that can transform T lymphocytes in vitro and is associated with certain T-cell neoplasms. Recent data suggest that, in the United States, patients with acquired immunodeficiency syndrome (AIDS), homosexual men with lymphadenopathy, and hemophiliacs have had significant exposure rates to HTLV, whereas matched and unmatched control American subjects have rarely been exposed to this agent. In the present experiments, T cells specifically reactive against HTLV were propagated from a patient whose HTLV-bearing lymphoma was in remission. The T cells were cloned in the presence of the virus and an HTLV-specific cytotoxic T-cell clone was isolated. This clone was infected and transformed by the virus, with one copy of an HTLV-I provirus being integrated into the genome. This T-cell clone did not exhibit the normal dependence on T-cell growth factor (interleukin-2) and proliferated spontaneously in vitro. Exposure of the clone to HTLV-bearing, autologous tumor cells specifically inhibited its proliferation and resulted in its death. These results may have implications for HTLV-associated inhibition of T-cell responses.
Acquired Immunodeficiency Syndrome↗
Leydig cell hyperplasia in cryptorchid patients: quantitative evaluation of Leydig cells in undescended and contralateral scrotal testes.
Leydig cell number was evaluated quantitatively in testicular biopsies from post-pubertal cryptorchid patients and normal controls. For this quantitative evaluation we used the following method. This is based on the determination of the total number of Leydig cells, Leydig cell clusters and seminiferous tubules in the entire histologic sections of each biopsy and the determination of the following indices; mean Leydig cells per tubule, mean Leydig cell clusters per tubule and mean Leydig cells per cluster. In addition, the numbers of Sertoli cells were counted, and Leydig-Sertoli cell ratio was also determined. These indices were correlated with each other. All indices were significantly elevated not only in undescended but in contralateral scrotal testes of the cryptorchid patients in comparison to those in normal controls. Between undescended and descended scrotal testes of the same individual patients, those indices were significantly higher in the descended scrotal testes than in the undescended ones. Thus, Leydig cell hyperplasia was noted in the testes of post-pubertal cryptorchid patients, and was more prominent in the contralateral scrotal testes than in the undescended ones.
Adolescent↗
[Statistical study on tumors of the urinary bladder--clinical and pathological aspects of 228 cases].
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Adult↗
Protection of T cells against infectivity and cytopathic effect of HTLV-III in vitro.
A recently discovered member of the human T-cell leukemia virus (HTLV) family of retroviruses has been etiologically linked to the acquired immunodeficiency syndrome (AIDS). This virus, which has been designated HTLV-III, is tropic for OKT4+ (helper/inducer) T-cells. Moreover, the virus is cytopathic for these cells. Suramin is a drug used in the therapy of Rhodesian trypanosomiasis and onchocerciasis, and it inhibits the reverse transcriptase of a number of retroviruses including HTLV-III. In the present work, we report our findings that suramin can block the in vitro infectivity and cytopathic effect of HTLV-III at doses that are clinically attainable in human beings. We believe these results may have relevance in planning experimental therapeutic strategies for various diseases associated with members of the HTLV-family of pathogenic human retroviruses.
Acquired Immunodeficiency Syndrome↗