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Biomedical subjects

H Mitsuya

Publications and source records attributed to H Mitsuya.

At least 199 records · Page 11Linked to original sources
PubMed1988

Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells.

The first step in the infection of human T lymphocytes by human immunodeficiency virus type 1 (HIV-1) is attachment to the target cell receptor, the CD4 antigen. This step may be vulnerable to attack by antibodies, chemicals, or small peptides. Dextran sulfate (molecular weight approximately 8000), which has been given to patients as an anticoagulant or antilipemic agent for more than two decades, was found to block the binding of virions to various target T lymphocytes, inhibit syncytia formation, and exert a potent inhibitory effect against HIV-1 in vitro at concentrations that may be clinically attainable in human beings. This drug also suppressed the replication of HIV-2 in vitro. These observations could have theoretical and clinical implications in the strategy to develop drugs against HIV types 1 and 2.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

An immunochemical and immunohistochemical study of S100 protein in renal cell carcinoma.

The authors localized S100 protein in renal tubules and renal cell carcinoma by immunohistochemical study and quantitative analysis by enzyme immunoassay. The alpha subunit of S100 protein (S100-alpha) was localized in epithelial cells of proximal tubules, thin limbs of loops of Henle, collecting tubules, and a few of Bowman's capsules. The beta subunit (S100-beta) was immunostained in the distal tubules, thick and thin loops of Henle, collecting tubules, and a few proximal tubules. In renal cell carcinoma, S100-alpha was immunohistochemically demonstrated in 82% (41/50) of patients including sarcomatoid variants, whereas S100-beta was detected in 46% (23/50). Both the number of positively stained tumor cells and the staining intensity were greater in S100-alpha than in S100-beta. Concentrations of S100-alpha in the cortex were 80.3 +/- 22.5 ng/mg protein (n = 7), whereas those of renal cell carcinoma were 387 +/- 533 ng/mg protein (n = 19), i.e., about five times higher. Concentrations of S100-beta in both normal kidney (1.96 +/- 0.74 ng/mg protein) and renal cell carcinoma (2.05 +/- 2.16 ng/mg protein) were much lower than those of S100-alpha. The authors also localized S100-alpha and S100-beta in tissues of other renal tumors and tumors arising from other organs. S100a0 appears to be a useful immunohistochemical marker for renal cell carcinoma.

Adenoma↗
PubMed1988

1-(2,3-Anhydro-beta-D-lyxofuranosyl)cytosine derivatives as potential inhibitors of the human immunodeficiency virus.

We report here that 1-(2,3-anhydro-beta-D-lyxofuranosyl)cytosine has activity against the human immunodeficiency virus in vitro. A number of 2',3'-anhydro-beta-D-lyxofuranosyl nucleoside derivatives were prepared, but none had the activity of the title compound. New efficient procedures were developed for the synthesis of 3'-deoxy-3'-alkyl- and 3'-deoxy-beta-D-arabinosylpyrimidine derivatives.

Ancitabine↗
PubMed1988

AIDS therapies.

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Acquired Immunodeficiency Syndrome↗
PubMed1988

Adenallene and cytallene: acyclic-nucleoside analogues that inhibit replication and cytopathic effect of human immunodeficiency virus in vitro.

Although several antiretroviral compounds are already known, almost no acyclic nucleoside derivatives lacking an oxacyclopentane have been reported to exert significant inhibition against human immunodeficiency virus type 1 (HIV-1) in vitro. We found two unsaturated acyclic nucleoside derivatives, adenallene [9-(4'-hydroxy-1',2'-butadienyl)adenine] and cytallene [1-(4'-hydroxy-1',2'-butadienyl)cytosine], that protect various CD4+ T-cell lines from the infectivity and cytopathic effect of HIV-1. These compounds inhibit the expression of HIV-1 gag-encoded protein and suppress viral DNA synthesis at concentrations that do not affect functions of normal T cells in vitro. They also inhibit the in vitro infectivity of another human retrovirus, HIV-2. Further in vitro analyses of the anti-HIV-1 activity revealed that the presence of two cumulated double bonds between the 1' and 2' carbons and between the 2' and 3' carbons confers antiretroviral activity in certain pyrimidine or purine derivatives containing a four-carbon chain. We have also found that the 4'-hydroxyl group is critical for the in vitro anti-HIV activity of adenallene. Our observations may provide structure-activity relationships for acyclic nucleoside analogues and may be of value in developing a new class of experimental drugs for the therapy of HIV-related diseases.

Adenine↗
PubMed1988

Inhibition of infectivity and replication of HIV-2 and SIV in helper T-cells by 2',3'-dideoxynucleosides in vitro.

We have previously shown that 2',3'-dideoxynucleosides and their derivatives are potent inhibitors of the infectivity and cytopathic effect mediated by human immunodeficiency virus type-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Recently a new group of retroviruses has been found in individuals originating from the western part of Africa. One member of this group is human immunodeficiency virus type-2 (HIV-2), previously designated lymphadenopathy-associated virus type-2 (LAV-2), found in patients with an AIDS-like illness. In this report, we show that 2',3'-dideoxynucleosides including 3'-azido-2',3'-dideoxythymidine (AZT) can significantly inhibit the infectivity and/or cytopathic effect of these retroviruses in vitro. Current data provide a rationale for considering 2',3'-dideoxynucleosides and their derivatives as experimental antiviral agents in individuals with illnesses caused by these new retroviruses.

Cytopathogenic Effect, Viral↗
PubMed1988

Treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex with a regimen of 3'-azido-2',3'-dideoxythymidine (azidothymidine or zidovudine) and acyclovir. A pilot study.

On the basis of observation that acyclovir potentiates the in-vitro antiviral activity of 3-azido-2',3'-dideoxythymidine (also known as azidothymidine or zidovudine) against human immunodeficiency virus (HIV), we administered a regimen of azidothymidine and acyclovir to eight patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. An oral regimen of 100 mg of azidothymidine and 800 mg of acyclovir every 4 hours was in general well tolerated, with the principal toxicity being megaloblastic erythroid changes. The pharmacokinetics of the two drugs were independent of each other. Six patients received the drug combination for at least 10 weeks; all had increased numbers of T4+ lymphocytes (P = 0.028), and two of three assessable patients had reversal of anergy. Two patients tested positive for serum HIV p24 antigen at entry, but became negative with treatment. Data for this small group suggest that this drug combination can be tolerated in patients with severe HIV infections; this study can be used as a basis for larger studies of this drug combination.

AIDS-Related Complex↗
PubMed1988

[A study of postoperative adjuvant chemotherapy of advanced urinary epithelial cancer].

The effect of postoperative adjuvant chemotherapy was studied in 22 cases of advanced urinary epithelial cancer. Vincristine, mitomycin C and bleomycin (VMB) was administered in combination to 9 prophase cases from December, 1980 to March, 1982 and cis-dichlorodiamine platinum, peplomycin and mitomycin C (PPM) in combination to 13 anaphase cases from April, 1982 to November, 1984. The site was renal pelvic cancer in 3 cases, cancer of the ureter in 3 cases, cancer of the bladder in 13 cases, cancer of the pelvis, ureter, and bladder in 1 case, and recurrence of pelvic cancer following bladder cancer in 2 cases. The degree of invasion was pTa in 2 cases, pT1 in 1 case, pT2 in 1 case, pT3 in 11 cases and pT4 in 5 cases. Lymph node metastasis had occurred in 9 cases, no metastasis in 8 cases and it was unclear in the remaining 6 cases. The mean observation period was 16.5 months; 10 patients were alive without any tumors, one patient was alive with a tumor, 11 patients died of cancer, and one patient died intercurrently. The mean postoperative survival period in the mortality cases was 14.5 months. According to the classified type of chemotherapy received, there were 3 out of 9 cases (33.3%) who survived without tumors after receiving VMP and 7 out of 13 cases (53.8%) in the PPM group who survived without tumors. Although a simple comparison cannot be made, it appears that PPM therapy is superior. No severe side-effects were observed.

Aged↗
PubMed1988

2',3'-Dideoxyadenosine is selectively toxic for TdT-positive cells.

The 2',3'-dideoxynucleosides (ddNs) are currently undergoing clinical evaluation as antiretroviral agents in HIV-infected individuals. When phosphorylated, the ddNs (ddNTPs) function as chain-terminating substrate analogues with reverse transcriptase, thereby inhibiting HIV replication. These nucleoside analogues can also inhibit, by chain-terminating additions, the primitive lymphoid DNA polymerase, terminal deoxynucleotidyl transferase (TdT). To determine the effect of possible intracellular chain-terminating additions of ddNMPs by TdT, we exposed a series of TdT-positive and TdT-negative cell lines to 2',3'-dideoxyadenosine (ddA), a representative ddN. At ddA concentrations 25-fold higher than required for inhibition of HIV replication, progressive dose-related cytotoxicity was observed in the TdT-positive cell lines. This was accentuated by the adenosine deaminase inhibitor Coformycin (CF), presumably by enhancing the intracellular generation of ddATP from ddA. A central role of TdT in mediating the ddA/CF cytotoxicity was suggested by studies in a pre-B-cell line rendered TdT positive by infection with a TdT cDNA-containing retroviral vector. After a 48-hour continuous exposure period to 250 mumol/L ddA and 30 mumol/L CF, 30% cell death was observed in the TdT-negative parental line, whereas 90% cell death was observed in the TdT-positive daughter line. Exposure of fresh TdT-positive leukemic cells to ddA/CF for 72 hours ex vivo resulted in cytotoxicity (six cases of acute lymphocytic leukemia [ALL]) while not affecting TdT-negative acute leukemic cells (six cases). We conclude that ddA/CF selectively damages TdT-positive cells, presumably by chain-terminating additions of ddAMP, and that this may have therapeutic relevance in TdT-positive malignant disease.

Cell Division↗
PubMed1988

[Clinical effects of terodiline hydrochloride on urinary frequency and sense of residual urine--a double blind clinical trial using flavoxate hydrochloride as a control].

A double blind clinical trial was performed as a multicenter study to determine the usefulness of terodiline hydrochloride (HCl), an anticholinergic and calcium antagonistic agent, for urinary frequency or sense of residual urine in patients with psychogenic diseases, chronic prostatitis or chronic cystitis. Either 24 mg of terodiline HCl a day or 600 mg of flavoxate HCl a day was given for 4 weeks. One hundred and ninety-nine patients completed the test. The final global improvement rating was 70% in patients given terodiline HCl and 48% in patients given flavoxate HCl. The difference was statistically significant (p less than 0.01). Diurnal and nocturnal urinary frequency and urinary incontinence were less in patients given terodiline HCl than in patients given flavoxate HCl (p less than 0.01). No difference was noted between the two agents in relieving sense of residual urine. Compared with the control period, the average urinary frequency decreased 2.0 times a day in patients given terodiline HCl and 0.7 times in patients given flavoxate HCl. The difference was statistically significant (p less than 0.01). Adverse effects were observed in 12% of the patients given terodiline HCl and in 16% of the patients given flavoxate HCl. They included thirst, difficult urination, constipation, slight increase of serum GOT, GPT or alkaline phosphatase, and so forth. They disappeared with discontinued use of the agent. The global utility rating was 68% in patients given terodiline HCl and 45% in patients given flavoxate HCl, the difference being significant (p less than 0.01). These results indicate that terodiline HCl is useful for the treatment of urinary symptoms in patients with psychogenic diseases, chronic prostatitis or chronic cystitis.

Adolescent↗
PubMed1987

The use of an HTLV-I-infected human T-cell line (ATH8) in an interleukin-2 bioassay.

Biological interleukin-2 (IL-2) assays require cells that proliferate only in the presence of IL-2. The most often used human cells for this purpose have been phytohaemagglutinin (PHA)-stimulated buffy coat lymphocytes made dependent on IL-2. The results obtained by this T-blast method have not been easily reproducible and/or comparable due to differences in individual buffy coat batches. Murine cytotoxic T-cell lines (CTLL and CTLL-2) have been widely used in human IL-2 assays, but there remains a need for a human cell line. We have developed an IL-2 bioassay, based on the use of a human HTLV-I-infected Th-cell line, ATH8. These cells express IL-2 receptor and are totally dependent on extrinsic IL-2 for proliferation. The results of the ATH8 IL-2 assay were reproducible and comparable to those obtained with successful T-blast assays. ATH8 cells do not require a prolonged culture period before they are suitable for the IL-2 assay as do T-blasts.

Biological Assay↗
PubMed1987

Activation of interleukin-2 receptor gene by forskolin and cyclic AMP analogues.

Forskolin (FK), a reversible activator of adenylate cyclase, markedly enhanced the expression of interleukin-2 receptor (IL-2-R) on a human natural killer (NK)-like cell line, YT. The FK-induced increase in IL-2-R on YT cells closely correlated with an increase in intracellular cyclic AMP (cAMP) level, and was mimicked by dibutyryl cyclic AMP (dbcAMP). FK induced both high and low affinity IL-2-R on the cells. Using a cDNA for the IL-2-R as a probe, the FK-induced IL-2-R expression was shown to be associated with an increase in IL-2-R mRNA. FK also enhanced the IL-2-R expression on a human T lymphotrophic virus I (HTLV-I) positive T-cell line (YTA-1H) and augmented the phorbol ester-induced expression of IL-2-R on HTLV-I negative T-cell lines (HSB-2 and HPB-ALL). These results suggest the possibility that the stimulation of adenylate cyclase may serve as a pathway leading to activation of the IL-2-R gene in certain types of lymphocytes.

Adenylyl Cyclases↗