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Biomedical subjects

H Mitsuya

Publications and source records attributed to H Mitsuya.

At least 235 records · Page 13Linked to original sources
PubMed1987

[A case of congenital unilateral multicystic kidney with renal matrix calculi].

A forty-two-year-old man was seen with right lumbar pain. Physical examination revealed a right flank mass. Conventional excretory urography showed lack of right renal function, whereas left kidney was visualized. Right nephrectomy was performed. A cluster of several different sized cysts was disclosed in the right renal region. The renal surface was smooth. The removed kidney weighed 1,150 g. The ureter was completely obstructed at the ureteropelvic junction. Cysts were filled with matrix calculi. Pathological examination showed dysplastic glomeruli and primitive tubules within loose embryonic mesenchyme between two cysts whose walls consisted of smooth muscle strands and connective tissue. The final diagnosis was a congenital unilateral multicystic kidney with renal matrix calculi. The multicystic kidney is the most common form of renal cystic disease in infancy. However, few cases in adults have been reported. The diagnostic approach, treatment and outcome of a congenital unilateral multicystic kidney are discussed.

Adult↗
PubMed1987

[Inhibitory effect of a calcium entry blocker (verapamil) on detrusor muscle contractility: feasibility of clinical application].

Effects of a Ca2+ entry blocker (verapamil) on the contractility of the bladder detrusor muscle of rabbits were investigated in vitro and in vivo. In experiments using smooth muscle strips from the bladder detrusor, isometric tension changes of the strips following drug addition were recorded. The contractions of the strips induced by acetylcholine (10(-8)-10(-2)M), prostaglandin E2, F2-alpha (3 X 10(-8)-3 X 10(-5)M) or electric stimulation were significantly inhibited dose-dependently by pretreatment of the strips with verapamil (10(-7), 10(-6)M). In in vitro experiments using whole bladder preparations, the spontaneous contractile activity and the contraction induced by acetylcholine (10(-6)M) were monitored. Both activities were inhibited in a time-dependent manner after the intravesical instillation of 7.5 mg verapamil. The amplitude of the spontaneous contraction and responses to acetylcholine, 90 minutes after the instillation, were reduced to 10% and 38% of the control levels (before the instillation), respectively. The detrusor contractility was still inhibited 2 hours after the removal of verapamil from the bladder. During in vivo experiments, changes in intravesical pressure and systemic arterial pressure were monitored. Sixty minutes after the intravesical instillation of 10 mg verapamil, the rise of the intravesical pressure following the pelvic nerve stimulation was inhibited to 18% of the control level, whereas the systemic arterial pressure was not affected. Verapamil is suggested to have potent inhibitory effects on the detrusor muscle contraction, and the intravesical instillation of verapamil to inhibit detrusor contractility without affecting the cardiovascular status.

Animals↗
PubMed1987

[A case of priapism caused by disseminated intravascular coagulopathy].

A case is presented of priapism resulting from disseminated intravascular coagulopathy (DIC), which was diagnosed by pathological studies of the amputated penis and skin biopsy. To our knowledge, this is the first case reported in Japan. This 72-year-old-man visited a hospital complaining of fever and cough, and was administrated for treatment of bronchitis and liver cirrhosis. A few days after admission, multiple purpura with edema and pain appeared over the skin regions on the bilateral knee joint, foot joint and upper extremities. A week after purpura appeared, priapism began. Regardless of irrigation and aspiration of corpora cavernosa and glans-cavernosa-fistula creation, penile necrosis developed. We had to perform penile amputation. The pathology of the amputated penis and skin, and blood coagulative examination suggested that DIC resulted in priapism. DIC was controllable by the use of FOY and heparin. He was discharged and is an outpatient.

Aged↗
PubMed1987

Catheter-associated urinary tract infections in patients undergoing transurethral surgery.

A study of 75 patients undergoing transurethral surgery with relatively short-term urethral catheterization with a sterile closed gravity drainage system revealed a 72% over-all incidence of negative urine cultures after catheter removal. The combination of prophylactic use of antimicrobials and a standardized catheter care system is valuable for preventing catheter-associated bacteriuria.

Aged↗
PubMed1987

A case of primary carcinoma of the epididymis.

We present a rare case of primary carcinoma of the left epididymis in a 32-year-old man. Pathological diagnosis was anaplastic carcinoma of epididymis. The patient is alive and free of metastases 2 years after orchidectomy. Clinical and pathological aspects of epididymal carcinomas are discussed with reference to previously reported cases.

Adult↗
PubMed1986

Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects.

A variant of human T-lymphotropic virus type III (HTLV-III) is described that replicates but does not kill normal human T cells in vitro. This variant, designated X10-1, was derived from the genome of a cytopathic HTLV-III clone (pHXB2D) by excision of a 200-base pair segment in the 3' region of the virus, spanning the env and 3'-orf genes. Comparable variants with 55 to 109 base pairs deleted exclusively in 3'-orf produced, in contrast, virus that was extremely cytopathic. On the basis of these findings it is concluded that the 3'-orf gene is not required for cytopathogenicity or replication of HTLV-III. In addition, the results suggest that virus replication and cytotoxicity are not intrinsically coupled. Furthermore, since clone X10-1 retains the ability to trans-activate genes linked to the viral long terminal repeats, trans-activation per se is not responsible for T-cell killing by HTLV-III. These results also raise the possibility that the carboxyl terminus of the envelope gene of HTLV-III has a direct role in T-cell killing by this virus.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Aurintricarboxylic acid and Evans Blue represent two different classes of anionic compounds which selectively inhibit the cytopathogenicity of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus.

Aurintricarboxylic acid, an anionic triphenylmethane dye, and Evans Blue, an anionic compound structurally related to suramin, are, like suramin itself, inhibitors of human T-cell lymphotropic virus type III (HTLV-III)/-lymphadenopathy-associated virus (LAV) in vitro. These compounds may be targeted, at least in part, at the HTLV-III/LAV reverse transcriptase. The lack of any appreciable cytostatic action of aurintricarboxylic acid, Evans Blue and suramin against several murine and human cell lines, their inability to inhibit cellular DNA, RNA and protein synthesis, and their high lethal dose-50 (greater than or equal to 0.340 g/kg) for NMRI mice point to the selectivity of the compounds as inhibitors of HTLV-III/LAV.

Animals↗
PubMed1986

Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T-cell lymphotropic virus (HTLV-III)/lymphadenopathy-associated virus (LAV).

Suramin and various other selected compounds were evaluated for their in vitro inhibitory effects on the infectivity and replication of human T-cell lymphotropic virus (HTLV/III)/lymphadenopathy-associated virus (LAV). As parameters for infectivity and replication, respectively, we followed the cytopathic effect of HTLV-III/LAV on ATH 8 cells, a T-cell clone with high susceptibility to HTLV-III/LAV, and the expression of HTLV-III/LAV p24 gag protein in H9 cells infected with HTLV-III/LAV. As the most effective inhibitors of HTLV-III/LAV the following substances emerged (in order of decreasing activity): Evans Blue approximately equal to suramin greater than phosphonoformic acid greater than Direct Yellow 50. Several purine nucleoside analogues including vidarabine, tubercidin, neplanocin A, dihydroxypropyladenine, pyrazofurin and ribavirin were not inhibitory to HTLV-III/LAV. In our test systems, involving a high multiplicity of infection, HPA-23, previously reported to be effective against LAV reverse transcriptase, showed no inhibitory effect on HTLV-III/LAV infectivity for ATH 8 cells and proved only weakly inhibitory to HTLV-III/LAV replication in H9 cells. Thus, among the anionic dyes that are structurally related to suramin, compounds were found which were as active as suramin itself, if not more so.

Animals↗
PubMed1986

An autoreactive T cell clone that can be activated to provide both helper and suppressor function.

To understand further the biologic significance of the autologous mixed lymphocyte reaction, we determined the functional properties of autoreactive T cell lines and clones. Initially, we found that cells in an uncloned autoreactive Leu-3+ T cell line helped immunoglobulin production when added to cultures containing fresh T and non-T cells in the absence of pokeweed mitogen (PWM) but suppressed immunoglobulin production in the same cultures in the presence of PWM. To explain this phenomenon, we studied the immunoregulatory potential of an autoreactive T cell clone termed MTC-4. This clone bore the phenotype Leu-3+, 2-, 8-, 11-, DR+ and underwent proliferation when co-cultured with autologous, but not allogeneic non-T cells. Of interest, the immunoregulatory potential of the MTC-4 cells varied according to how the cells were activated. When MTC-4 cells were cultured with autologous non-T cells in the absence of antigen or mitogen (unactivated non-T cells), polyclonal immunoglobulin production (detected by reverse PFC assay) was observed. This helper activity was MHC-restricted in that it was elicited only by autologous non-T cells or MHC-matched allogeneic non-T cells; however, once activated by autologous non-T cells, it could also help allogeneic non-T cells. In contrast, when MTC-4 cells were cultured with autologous non-T cells in the presence of PWM (activated non-T cells), immunoglobulin production was greatly suppressed. This suppression was also observed when MTC-4 cells were added to cultures containing exogenous T cell help (such as that provided by autologous fresh T cells) and was not due to a direct effect of PWM on the T cell clone, because preincubation of MTC-4 cells with PWM before culture with non-T cells did not result in suppression. On the basis of these data, we conclude that autoreactive T cells can have dual immunoregulatory function that is manifest, at least in part, at the single cell level. Moreover, these regulatory functions are differentially elicited depending on the state of activation of the stimulating autologous non-T cells: when stimulated by MHC antigens present on unactivated B cells, they provide helper activity; and when stimulated by MHC antigens present on activated B cells, they act as suppressor cells. Autoreactive T cells with dual regulatory potential appear to make up a substantial proportion of all autoreactive T cells and are cells that are uniquely adapted to maintain immunologic homeostasis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells.

We studied the configuration and expression of the gene encoding the beta chain of the T cell receptor (TCR beta) in cell lines and primary tumor cells infected by the human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I). Most of the cell lines and all the primary tumor cells showed rearrangement of the TCR beta gene, and in each case the rearrangement was distinct. The majority of cases examined were clonal with respect to a particular TCR beta gene rearrangement. Primary tumor cells from one case (SD) were found to have a tandem duplication of a portion of chromosome 7; this appears to have resulted in the presence of three alleles of the TCR beta gene, each of which is arranged differently. This suggests that the chromosomal abnormality, and possibly infection by HTLV-I, occurred before TCR beta gene rearrangement. Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I. Cloned T cells of known antigen specificity that are infected by HTLV-I in vitro show impairment of immune function, including loss of antigen-specific responsiveness and the acquisition of alloreactivity. Comparison of the configuration of the TCR beta gene before and after infection revealed no changes detectable by Southern blot analysis. Levels of expression of the TCR beta gene at the mRNA level and surface expression of the T3 complex were also not significantly altered, suggesting that changes in immune function cannot be attributed to quantitative changes in the TCR molecule. The configuration of the TCR beta gene in primary tumor cells infected by HTLV-I was compared with that in the derived cell lines. In all pairs examined, the configuration in the primary tumor cells was different from that in the cell lines, strongly suggesting that the cells that grow in culture are not the original neoplastic cells.

Antigens, Neoplasm↗
PubMed1986

Evidence for contractility of the human seminiferous tubule confirmed by its response to noradrenaline and acetylcholine.

The experiments reported here demonstrate for the first time that the isolated human seminiferous tubule is capable of undergoing contraction after exposure to noradrenaline and acetylcholine. Isoproterenol produces a relaxation of the seminiferous tubule. It is indicated that there are the adrenergic alpha and beta receptors and muscarinic receptors in the myoid cells of human seminiferous tubules.

Acetylcholine↗
PubMed1986

Successful treatment of oligospermic and azoospermic men with alpha 1-blocker and beta-stimulator: new treatment for idiopathic male infertility.

We studied the effect of oral administration of alpha 1-blocker and beta-stimulator on 20 idiopathically infertile men. Bunazosin (alpha 1-blocker, 2 mg/day) and procaterol (beta-stimulator, 100 micrograms/day) were given orally twice daily for 5 months. The administration of alpha 1-blocker and beta-stimulator elicited an increase in sperm output and seminal volume in 16 patients (80%). The increase in sperm output seems to be associated with relaxations of myoid cells, which lead to dilatation of stenotic areas of seminiferous tubules, occurring discontinuously, and subsequent maintenance of good tubular fluid flow. No adverse effects were observed in this series.

Adrenergic alpha-Antagonists↗
PubMed1986

Remarkable responses of metastatic renal cell cancer in multiple organs treated with alpha-interferon.

We report a case of renal cell carcinoma with metastases in the lungs, humerus and brain, which we treated with alpha-interferon. After a transperitoneal nephrectomy the patient received a series of intramuscular injections of alpha-interferon every 2 days. Two months after the initial therapy complaints of pain in the humeral bone gradually decreased and the palpable mass in the right brachial region disappeared completely. A computerized tomography scan revealed only the scar of the intracranial metastasis. Most of the pulmonary lesions disappeared 4 months later except for the metastasis at the apex of the left lung.

Adult↗
PubMed1986

Correction of adenosine deaminase deficiency in cultured human T and B cells by retrovirus-mediated gene transfer.

A retroviral vector called SAX, containing the cloned human cDNA for adenosine deaminase (ADA), has been constructed and used to introduce the ADA gene into cultured T- and B-lymphocyte lines derived from patients with ADA deficiency. DNA analysis showed that the SAX vector was inserted intact into the T and B cells at approximately one copy per cell. The treated cells produced the characteristic isozymes of human ADA at a level similar to normal T and B lymphocytes. It is known that ADA-deficient lymphocytes are unusually sensitive to high levels of 2'-deoxyadenosine, and this is the mechanism thought to underlie the selective lymphocytotoxicity associated with ADA deficiency in vivo. Expression of the introduced ADA gene was sufficient to reverse the hypersensitivity of these genetically deficient lymphocytes to 2'-deoxyadenosine toxicity. These results support the suggestion that retroviral vector gene-delivery systems show promise for application to human gene therapy.

Adenosine Deaminase↗
PubMed1986

Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase.

The thymidine analog 3'-azido-3'-deoxythymidine (BW A509U, azidothymidine) can inhibit human immunodeficiency virus (HIV) replication effectively in the 50-500 nM range [Mitsuya, H., Weinhold, K. J., Furman, P. A., St. Clair, M. H., Nusinoff-Lehrman, S., Gallo, R. C., Bolognesi, D., Barry, D. W. & Broder, S. (1985) Proc. Natl. Acad. Sci. USA 82, 7096-7100]. In contrast, inhibition of the growth of uninfected human fibroblasts and lymphocytes has been observed only at concentrations above 1 mM. The nature of this selectivity was investigated. Azidothymidine anabolism to the 5'-mono-, di-, and -triphosphate derivatives was similar in uninfected and HIV-infected cells. The level of azidothymidine monophosphate was high, whereas the levels of the di- and triphosphate were low (less than or equal to 5 microM and less than or equal to 2 microM, respectively). Cytosolic thymidine kinase (EC 2.7.1.21) was responsible for phosphorylation of azidothymidine to its monophosphate. Purified thymidine kinase catalyzed the phosphorylations of thymidine and azidothymidine with apparent Km values of 2.9 microM and 3.0 microM. The maximal rate of phosphorylation with azidothymidine was equal to 60% of the rate with thymidine. Phosphorylation of azidothymidine monophosphate to the diphosphate also appeared to be catalyzed by a host-cell enzyme, thymidylate kinase (EC 2.7.4.9). The apparent Km value for azidothymidine monophosphate was 2-fold greater than the value for dTMP (8.6 microM vs. 4.1 microM), but the maximal phosphorylation rate was only 0.3% of the dTMP rate. These kinetic constants were consistent with the anabolism results and indicated that azidothymidine monophosphate is an alternative-substrate inhibitor of thymidylate kinase. This conclusion was reflected in the observation that cells incubated with azidothymidine had reduced intracellular levels of dTTP. IC50 (concentration of inhibitor that inhibits enzyme activity 50%) values were determined for azidothymidine triphosphate with HIV reverse transcriptase and with immortalized human lymphocyte (H9 cell) DNA polymerase alpha. Azidothymidine triphosphate competed about 100-fold better for the HIV reverse transcriptase than for the cellular DNA polymerase alpha. The results reported here suggest that azidothymidine is nonselectively phosphorylated but that the triphosphate derivative efficiently and selectively binds to the HIV reverse transcriptase. Incorporation of azidothymidylate into a growing DNA strand should terminate DNA elongation and thus inhibit DNA synthesis.

Antiviral Agents↗
PubMed1986

Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides.

Human T-lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus (LAV) is a a newly discovered lymphotropic retrovirus that is cytopathic for helper/inducer T cells in vitro. This virus is the etiologic agent of the acquired immunodeficiency syndrome and related diseases. In the current study, we tested the capacity of purine and pyrimidine nucleoside derivatives to inhibit the infectivity and cytopathic effect of human T-lymphotropic virus type III in vitro. With the ribose moiety of the molecule in a 2',3'-dideoxy configuration, every purine (adenosine, guanosine, and inosine) and pyrimidine (cytidine and thymidine) nucleoside tested suppressed the virus, although the thymidine derivative seemed to have substantially less activity in our system than the others. In general, we observed essentially complete suppression of the virus at doses that were lower by a factor of 10 to 20 than those needed to inhibit the proliferation of the target T cells and the immune reactivity of normal T cells in vitro. An analysis of five adenosine congeners, which differed only in the sugar moiety, revealed that reduction (an absence of hydroxyl determinants) at both the 2' and 3' carbons of the ribose was necessary for an anti-viral effect, and an additional reduction at the 5' carbon nullified the anti-viral activity. These observations may be of value in developing a new class of experimental drugs for the therapy of human T-lymphotropic virus type III infections.

Antiviral Agents↗