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Biomedical subjects

H Mitsuya

Publications and source records attributed to H Mitsuya.

At least 217 records · Page 12Linked to original sources
PubMed1987

Elastic fibers in tunica propria of undescended and contralateral scrotal testes from cryptorchid patients.

Elastic fibers in the tunica propria of the testes from cryptorchid patients and normal fertile adults were examined by light (Weigert resorcin-fuchsin stain) and electron microscopic techniques. In the testes from normal fertile adults, elastic fibers were proved to exist in the tunica propria by light and electron microscopy, and were located in the fibrous and cellular layers of the tunica propria. In the undescended testes from the cryptorchid patients, during prepubertal and pubertal periods, elastic fibers could not be visualized in the tunica propria, but were found after puberty. The positive Weigert reaction of the tunica propria in the undescended testes from postpubertal cryptorchid patients, however, was markedly weaker than that in normal control patients, suggesting diminution of elastic fibers. This diminution of elastic fibers in the undescended testes from postpubertal cryptorchid patients was also substantiated by electron microscopy. However, in the contralateral scrotal testes, elastic fibers appeared during puberty and were observed after puberty in the same manner as in normal testes. Thus, the present study suggested retarded appearance of elastic fibers in puberty and impaired development of those fibers after puberty, in the undescended testes of cryptorchid patients.

Adolescent↗
PubMed1987

Potential anti-AIDS drugs. 2',3'-Dideoxycytidine analogues.

5-Substituted 2',3'-dideoxycytidine analogues have been synthesized and evaluated in vitro for their capabilities to protect T4+ lymphocytes from the cytopathic effects of the HTLV-III/LAV (HIV) virus, the causative agent of acquired immunodeficiency syndrome (AIDS). These analogues were designed to be more lipophilic than 2',3'-dideoxycytidine (ddC) in order to enhance central nervous system penetration. Earlier reports had shown that ddC is a potent protective agent. When ddC is substituted at the 5-position with either methyl or bromo substituents, activity is completely abolished. However, when the substitution is fluoro (5-F-ddC), both activity and potency are retained. 2',3'-Dideoxy-5-azacytidine is also protective but more toxic than ddC or 5-F-ddC. In a different approach, an attempt was made to utilize ddCMP, ddTMP, and ddAMP as preformed nucleotides in order to circumvent the generally low level of phosphorylation achieved with dideoxynucleosides which function as relatively poor substrates for the cellular kinases. Only ddAMP is as active as its nucleoside precursor. Because ddAMP is not more active than ddA at low concentrations, it is possible that the active agent is ddA which is generated from ddAMP prior to cell entry.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus.

Nuclease-resistant phosphorothioate analogs of certain oligodeoxynucleotides have been tested in vitro as antiviral agents against human immunodeficiency virus (HIV) in human T cells. Phosphorothioate analogs complementary to HIV sequences, as well as noncomplementary analogs including homooligomers, exhibited potent antiviral activity. The antiviral activity was related to the base composition of the analogs, and longer phosphorothioates were more effective than shorter ones. A 28-mer phosphorothioate oligodeoxycytidine (S-dC28) at a concentration of 1 microM exhibited potent antiviral activity and inhibited de novo viral DNA synthesis as shown by Southern blot analysis. However, S-dC28 failed to inhibit gag expression in chronically infected T cells assessed by immunofluorescent assay at concentrations up to 25 microM. An N3-methylthymidine-containing phosphorothioate analog, which does not hybridize efficiently in vitro to complementary normal DNA, showed no antiviral activity. A 14-mer phosphorothioate oligodeoxycytidine (S-dC14) synergistically enhanced the antiviral activity of 2',3'-dideoxyadenosine, an anti-HIV nucleoside. Therefore, phosphorothioate analogs of oligodeoxynucleotides could represent a unique class of experimental therapeutic agents against the acquired immunodeficiency syndrome and related diseases. However, their mechanism of action is likely to be complex.

Base Sequence↗
PubMed1987

Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2',3'-dideoxynucleosides in vitro.

We report that 2',3'-dideoxyadenosine and 2',3'-dideoxycytidine inhibit retroviral DNA synthesis and mRNA expression in T cells exposed to the virus that causes acquired immunodeficiency syndrome, and afford such cells long-term protection in vitro under conditions of substantial viral excess. Both 2',3'-dideoxyadenosine and 2',3'-dideoxycytidine appear to completely block reverse transcription from viral RNA to viral DNA. Viral mRNA expression is also not detected in cells protected by the drugs throughout 30 days of culture following exposure to the virus. Purine and pyrimidine analogues as 2',3'-dideoxynucleoside-5'-triphosphate serve as substrates for the human T-lymphotropic virus type III/lymphadenopathy-associated virus reverse transcriptase to elongate a DNA chain by one residue, after which the chain is terminated. Cloned normal helper/inducer T cells exposed to a cytopathic dose of the virus, but protected by the drugs, respond normally to specific antigen in vitro. These results suggest that the drugs could be promising agents for further studies in the experimental treatment of patients infected with retroviruses.

Antiviral Agents↗
PubMed1987

Broad spectrum antiretroviral activity of 2',3'-dideoxynucleosides.

Certain dideoxynucleosides have been shown to markedly inhibit the infectivity of human T-lymphotropic virus type III/lymphadenopathy-associated virus, the causative agent of acquired immunodeficiency syndrome (AIDS). Our present studies demonstrate that these drugs are broad spectrum antiretroviral agents capable of inhibiting the infectivity of evolutionarily divergent mammalian type C and animal lentiviruses. Under some conditions, virus infectivity could be inhibited by more than six orders of magnitude. However, the potency of these agents was shown to be greatly influenced by cell-specified determinants. Drug exposure during the initial 24 hr was almost as effective as prolonged treatment on the inhibition of a single cycle of virus infection and expression. Moreover, virus infection was shown directly to be inhibited at the level of proviral DNA synthesis. Thus the time period during which reverse transcription and provirus integration occur is the critical period required for drug action. Our findings have implications concerning strategies to be considered in attempts to utilize 2',3'-dideoxynucleosides in control and treatment of retrovirus-induced diseases of animals and humans.

Animals↗
PubMed1987

Complete nucleotide sequences of functional clones of the AIDS virus.

To examine the mechanism of lymphocytotoxicity induced by human T-lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV), an in vitro model has been developed. Introduction of an HTLV-III/LAV proviral clone, HXB2, into normal lymphocytes results in the production of virions and cell death. The complete nucleotide sequence of the proviral form of HXB2 has now been determined. Its structure is quite similar to that previously determined for HTLV-III/LAV clones whose biological capacities had not previously been demonstrated. The biological function of two additional clones of HTLV-III/LAV, BH10 and HXB3, are reported. Clone BH10 which lacks the 5' long terminal repeat sequences (LTR) and a portion of the 3' LTR is reconstituted by substituting the corresponding sequences of HXB2 and is shown to be capable of generating infectious cytopathic virions. Clone HXB3, which has been partially sequenced, is also found to be capable of producing lymphocytopathic virus. Clone HXB3 differs from HXB2 in its lack of a termination codon in 3' orf, demonstrating that 3' orf plays no major role in virus replication or cytopathic activity. These data provide the necessary background to allow the identification of viral determinants of replication, cytopathic activity, and antigenicity using these functional proviral clones.

Base Sequence↗
PubMed1987

Incontinence in female neurogenic bladders. Resolution by endoscopic bladder neck suspension.

Five incontinent females with neurogenic bladder diseases underwent endoscopic vesical neck suspension (Stamey procedure). Four patients have become dry on clean intermittent catheterisation and one has shown improvement. Bladder capacity was increased to a reasonable size in all patients. There has been no upper tract deterioration during the follow-up period of 3 to 25 months. We believe that the Stamey procedure is useful in alleviating urinary incontinence in neurogenic bladders provided that the bladder is drained regularly by intermittent catheterisation and that low detrusor compliance or detrusor hyper-reflexia is adequately managed.

Adolescent↗
PubMed1987

Epithelial membrane antigen as an immunohistochemical marker for transitional cell carcinoma of the urinary bladder.

Epithelial membrane antigen (EMA) was immunohistochemically localized in transitional cell carcinomas of the bladder to clarify EMA staining pattern's relationship to the histological grading and staging of tumors and patient prognosis. Formalin-fixed, paraffin-embedded sections from 101 patients with bladder carcinoma were stained by the indirect immunoperoxidase method. In the lower histological grade and stage of transitional cell carcinoma, the localization of EMA was restricted to the luminal surface of the superficial cells. Membrane and cytoplasmic staining of EMA was frequently found in the intermediate and basal layers of the tumor cells, and the incidence of cytoplasmic staining increased with advancing grade and stage. Stromal staining was frequently observed in cases of higher grade and stage. In addition, these distribution patterns of EMA were well correlated with patient survival. Thus, we differentiated three types of EMA distribution: a luminal type, with very good prognosis; a cytoplasmic type, with fair prognosis; and a stromal type, with relatively poor prognosis. These findings suggest that EMA distribution in bladder cancer could be a valuable indicator for histological grading or staging in pathological diagnosis and for predicting the survival of bladder cancer patients.

Aged↗
PubMed1987

Malignant fibrous histiocytoma arising from the renal capsule: report of a case.

We report a case of malignant fibrous histiocytoma arising from the renal capsule. The tumor was found during screening ultrasonography. Surgical excision and adjuvant chemotherapy consisting of cyclophosphamide, vincristine, adriamycin and actinomycin D were performed. There has been no recurrence as of 2 years and 4 months after the operation. We reviewed the 5 other cases of malignant fibrous histiocytoma arising from the renal capsule.

Histiocytoma, Benign Fibrous↗
PubMed1987

Pharmacological inhibition of in vitro infectivity of human T lymphotropic virus type I.

Human T lymphotropic virus type I (HTLV-I) is an exogenous RNA tumor virus etiologically linked to adult T cell leukemia and related diseases. In this paper, we describe that two 2',3'-dideoxynucleoside analogues, erythro 3'-azido-2',3'-dideoxythymidine (also called azidothymidine) and 2',3'-dideoxycytidine can inhibit the infectivity of HTLV-I against helper/inducer T cells in vitro. Both 2',3'-dideoxynucleoside analogues inhibited the overgrowth of target T cells, which was a consequence of virally mediated transformation, when they were exposed to the virus and cultured with the compounds. A profound decrease in the expression of HTLV-I gag-proteins was also observed. Moreover, we observed that the amount of proviral DNA detected in cellular DNA from the target T cells was substantially reduced when the cells were protected by the compounds against the virus and that at certain concentrations of the compounds the synthesis of viral DNA was completely suppressed. These results may be of value in developing a new pharmacological strategy for preventing the replication and possibly blocking the transmission of HTLV-I and related retroviruses in human beings.

DNA, Viral↗
PubMed1987

[Treatment of advanced testicular cancer].

Two patients with stage II, 12 patients with stage III advanced testicular cancer, were treated with a combination of CDDP, vinblastine and bleomycin. Four of the cases (28.6%) achieved a complete response and 6 (42.9%) achieved a partial response. The over all response rate was 71.4%. After CR, 2 cases (50%) showed relapse. Although the treatment confirms some efficacy of the drug regimen, the prognosis is poor in bulky metastasis. Early induction therapy with etoposide is necessary in cases of high volume metastasis.

Adult↗
PubMed1987

[Clinical study of bunazosin hydrochloride, an alpha 1-adrenergic blocker, in benign prostatic obstruction and neurogenic bladder dysfunction].

A newly developed alpha 1-adrenergic blocker, bunazosin hydrochloride (Detantol, Eisai) was clinically investigated in 17 patients with benign prostatic obstruction and 18 patients with neurogenic bladder dysfunction. Subjective symptoms improved in 11 of the 17 cases (64.7%) with prostatic obstruction and in 4 of the 10 cases (40%) with neurogenic bladder dysfunction. Dose-dependent subjective improvement was observed with dosages of 3 to 9 mg/day. A dosage of 12 mg/day did not improve subjective symptoms more than did the 9 mg/day dose. In prostatic obstruction, 7 of the 10 objective parameters improved significantly. However, for neurogenic bladder dysfunction, only two parameters improved significantly. Improvements in objective findings were generally dose-dependent in cases of prostatic obstruction, but not in neurogenic bladder dysfunction. Mild side effects, none of them serious, were reported in 9 of the total 35 cases (26%). They generally consisted of dizziness, nasal obstruction and headache. Comprehensive improvement, i.e., improvement of both subjective symptoms and objective parameters, occurred in 11 of the 17 cases (64.7%) of prostatic obstruction and 6 of the 18 cases (33.3%) of neurogenic bladder dysfunction.

Adolescent↗
PubMed1987

A study of cryptorchidism. III: The histochemistry of complex carbohydrates in the testes of cryptorchid patients.

The complex carbohydrates in the undescended and contralateral scrotal testes of patients with cryptorchidism, were examined by light microscopic histochemical methods, in comparison with those of normal testes. In the undescended testes, histochemical reactions for acidic and neutral complex carbohydrates were apparently weaker than in the normal testes, especially pronounced in the seminiferous tubular walls. In the germinal and supporting cells of the undescended testes, the amount of galactose residues in the complex carbohydrates decreased from the prepubertal to post-pubertal periods. Periodic acid-Schiff reaction also revealed a decrease in the glycogen content in the germinal and supporting cells of the undescended testes from pre-pubertal to post-pubertal periods.

Adolescent↗
PubMed1987

[Recurrence of transitional cell carcinoma in the left pelvis and ureter, and ileal conduit after total cystectomy: a case report].

A 63-year-old male with transitional cell carcinoma of the bladder underwent total cystectomy. Five years later sequential excretory urography and urinary cytologic examination revealed tumor recurrence in the left pelvis and ureter; left nephroureterectomy was performed in July, 1984. In December, 1985, he complained of macrohematuria and urinary cytology was positive. Ileal conduitgraphy showed filling defects at the bilateral uretero-ileal anastomosis, where two papillary lesions were disclosed by endoscopic examination. In January, 1986, total extirpation of the ileal conduit and reconstruction of a new ileal conduit was performed. Macroscopically the two lesions were found to be a papillary tumor at left uretero-ileal anastomosis and a polypoid tumor distal to right uretero-ileal anastomosis. Histological examination revealed both tumors to be grade II transitional cell carcinoma. This rare case is discussed and the literature is reviewed.

Anastomosis, Surgical↗