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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 721 records · Page 40Linked to original sources
PubMed1988

Potent and selective activity of 3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside, 3'-fluoro-2,6-diaminopurine-2',3'-dideoxyriboside, and 3'-fluoro-2',3'-dideoxyguanosine against human immunodeficiency virus.

Several sugar-modified 2,6-diaminopurine and guanine 2',3'-dideoxyribosides were synthesized and evaluated in vitro for their ability to inhibit the cytopathic effect and replication of human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). 3'-Azido-2,6-diaminopurine-2',3'-dideoxyriboside (AzddDAPR), 3'-fluoro-2,6-diaminopurine-2',3'-dideoxyriboside (FddDAPR), and 3'-fluoro-2',3'-dideoxyguanosine emerged as potent and selective anti-HIV agents in MT4 cells (50% effective antiviral dose: 0.3-4.5 microM). Their selectivity indexes, based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, were 157, 80, and 96, respectively, as compared to 106 for 2,6-diaminopurine-2',3'-dideoxyriboside (ddDAPR) and 132 for 2',3'-dideoxyadenosine (ddAdo), two other potent anti-HIV agents. The 9-beta-D-arabinoside and 9-beta-D-2'-deoxyxyloside derivatives of 2,6-diaminopurine were devoid of any antiretrovirus activity. Both AzddDAPR and FddDAPR, like the parent compounds ddDAPR and ddAdo, proved susceptible to deamination by beef intestine adenosine deaminase (Km, 11, 148, 29, and 73 microM, respectively). 2'-Deoxycoformycin, a potent inhibitor of adenosine deaminase, decreased the antiretrovirus and cytostatic activity of ddDAPR and FddDAPR to a greater extent than that of AzddDAPR. This suggests that ddDAPR and FddDAPR are primarily active as their guanine analogues, whereas AzddDAPR may be potentially active as a 2,6-diaminopurine derivative as well.

Adenosine Deaminase↗
PubMed1988

[The effects of localized therapy with postsurgical local recurrences of lung carcinoma and metastatic lung tumors--laser irradiation, IL-2+ LAK or ethanol injection].

Nd-YAG or Argon dye laser irradiations combined with radiotherapy were performed for lung cancer patients with central airway obstructions due to recurrences. Remarkable effects of immediate airway dilatation and reduction of symptoms were obtained after laser irradiations. IL-2 and LAK injections or ethanol injections into the peripheral recurrent or metastatic lung lesions. In one out of 5 patients after IL-2 and LAK injection, and in one out of 2 patients after ethanol injection, tumor size was reduced by 43% and 34%, respectively. IL-2 and/or LAK were injected into the pleural or pericardial spaces with malignant effusion, showing significant effects on a lung cancer patient with cancerous pericarditis who survived more than 9 months after this localized therapy. According to these results, these localized therapies may not always prove effective, but they should be applied to unresectable recurrent lung cancers or metastatic lung tumors in order to prolong survival with good quality of life.

Adenocarcinoma↗
PubMed1988

[A resected case of adenosquamous-carcinoma of the lung].

A resected case of an adenosquamous carcinoma of lung diagnosed from sputum and trans-bronchial-aspiration cytology is reported. The patient, a 39-year-old woman, was identified by mass screening testing for pulmonary cancer. Sputum cytology and trans-bronchial-aspiration cytology conducted by means of a bronchofiberscope revealed the presence of both an adenocarcinoma and squamous carcinoma cells. A histologic examination of the resected lung revealed the adenosquamous carcinoma. This case is very rare in having been diagnosed before surgery, and by sputum cytology which was very available.

Adenocarcinoma↗
PubMed1987

Ferritin selectively suppresses delayed-type hypersensitivity responses at induction or effector phase.

The effect of ferritin on the delayed-type hypersensitivity (DTH) response and Arthus-type reaction as assessed by footpad reaction using methylated human serum albumin, human serum albumin, or sheep red blood cells as antigens was investigated. Intraperitoneally administered ferritin was short acting and suppressed either induction or expression of DTH depending on the time of ferritin injection although it did not inhibit the antibody-mediated inflammatory response, the Arthus reaction. Investigation of ferritin's effect on the primary antibody response revealed that the number of IgG plaque-forming cells (PFC) was moderately decreased but IgM PFC were not. These results indicate that the afferent limb, ferritin selectively suppresses antigen presentation and/or clonal expansion of effector cells of cell-mediated immunity, but not that of the antibody response. Antigen presentation by Ia-positive cells and/or lymphokine-responsive inflammatory mononuclear cells at the efferent limb of DTH is suggested to be affected by ferritin. This conclusion is based upon the observations of successful TDTH effector cell transfer from sensitized but ferritin-treated donors and of successful reversal of ferritin-induced suppression of expression of DTH by supplementing normal bone marrow-derived cells containing Ia-positive ones. Thus our in vivo experimental system might be useful for the differential analysis of immunopathological lesions such as a T-cell-mediated, monocyte-dependent and an antibody-mediated inflammatory lesions.

Animals↗
PubMed1987

Enhancement by vasoactive intestinal peptide of experimental carcinogenesis induced by azoxymethane in rat colon.

The effects of vasoactive intestinal peptide (VIP) on the incidence and histology of colonic tumors induced by azoxymethane (AOM) were investigated in Wistar rats. Rats were given 20 micrograms/kg body weight of VIP every other day for 12 weeks and from experimental week 3, were given 10 weekly injections of 7.4 mg/kg body weight of AOM. The administration of VIP before and during AOM treatment resulted in a significant increase in the incidence of colonic tumors in week 40. Furthermore, it caused a significant increase in the labeling index of the colonic mucosa during AOM treatment. These findings indicate that VIP enhanced the development of colonic tumors. This effect may have been related to its effect in increasing proliferation of cells in the colonic mucosa during administration of the carcinogen.

Animals↗
PubMed1987

Selective inhibition of human immunodeficiency virus (HIV) by 3'-azido-2', 3'-dideoxyguanosine in vitro.

3'-Azido-2',3'-dideoxyguanosine (AzddGuo) is a potent and selective inhibitor of human immunodeficiency virus (HIV) in vitro. AzddGuo completely inhibits HIV-induced cytopathogenicity and viral antigen expression in MT-4 cells at a concentration of 5.0 microM. Its 50% effective dose for inhibiting HIV-induced cytopathogenicity is 1.4 microM, as compared to 6.4 microM for 2',3'-dideoxyadenosine (ddAdo). Thus, AzddGuo is approximately 4.6-fold more potent as an anti-HIV agent than ddAdo, one of the most promising compounds for the treatment of AIDS. However, AzddGuo is about 4.7 times more cytotoxic than ddAdo, so that its selectivity index, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, is almost the same as that of ddAdo (136 and 139, respectively).

Animals↗
PubMed1987

The 2',3'-dideoxyriboside of 2,6-diaminopurine selectively inhibits human immunodeficiency virus (HIV) replication in vitro.

The 2',3'-dideoxyriboside of 2,6-diaminopurine(ddDAPR) is, like 2',3'-dideoxyadenosine (ddAdo), a potent and selective inhibitor of human immunodeficiency virus (HIV) in vitro. The ddDAPR compound inhibits HIV antigen expression and HIV-induced cytopathogenicity in MT4 cells at a 50% effective dose (ED50) of 2.5-3.6 microM, as compared to 3.1-6.4 microM for ddAdo. Both compounds are endowed with a high selectivity index: 112 for ddDAPR and 139 for ddAdo. The 2',3'-unsaturated derivatives of ddDAPR and ddAdo, i.e. ddeDAPR and ddeAdo, are considerably more cytotoxic and less effective against HIV than the parental compounds. Like ddAdo, ddDAPR is only weakly inhibitory to the proliferation and DNA and RNA synthesis of a series of human B-lymphoblast, T-lymphoblast and T-lymphocyte cell lines. In contrast to ddAdo, which is rapidly deaminated by beef intestine adenosine deaminase at an initial velocity (Vi) of 145 mumol/mg protein/min, ddDAPR and ddeDAPR are poor substrates for the enzyme (Vi: 8 and 0.7 mumol/mg protein/min, respectively), which further contributes to the potential of ddDAPR as a chemotherapeutic agent against AIDS.

Adenosine Deaminase Inhibitors↗
PubMed1987

Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro.

2',3'-Dideoxythymidine (ddThd) and its 2',3'-unsaturated derivative 2',3'-dideoxythymidinene (ddeThd) are potent and selective inhibitors of human immunodeficiency virus (HIV) in vitro. When evaluated for their inhibitory effects on the cytopathogenicity of HIV in MT-4 cells, ddThd and ddeThd completely protected the cells against destruction by the virus at a concentration of 1 microM and 0.04 microM, respectively. In this aspect, ddeThd was about 5 times more potent than 2',3'-dideoxycytidine (ddCyd), one of the most potent and selective anti-HIV compounds now pursued for its therapeutic potential in the treatment of AIDS. ddThd and ddeThd also suppressed HIV antigen expression at 1 microM and 0.04 microM, respectively. Their selectivity indexes, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, were 120 (ddeThd) and greater than 625 (ddThd).

Antigens, Viral↗
PubMed1987

Preneoplastic and neoplastic growth of xenotransplanted lung-derived human cell lines using deepithelialized rat tracheas.

The human lung tumor-derived cell lines A549, Calu-1, Calu-3, HuT292, and SW900 and the transformed human bronchial epithelial cell line TBE-1, that was transfected with the v-Harvey-ras oncogene, were inoculated into deepithelialized Fisher 344 rat tracheas (5 X 10(5) cells/trachea). After the ends of the tracheas were sealed, the tracheas were transplanted into s.c. tissues of nude mice. In a parallel experiment, 1 X 10(6) cells from each of these cell lines were injected s.c. Histological examination of the tracheal transplants 2, 4, 8, 12, and 16 weeks after cell inoculation proved to be of greater usefulness than either clinical or histological observation of the s.c. injection sites. A549, Calu-1, and TBE-1 produced intratracheal neoplastic nodules as early as 2 weeks after cell inoculation. Calu-3, HuT292, and SW900 grew relatively slowly in the tracheas, and simple or stratified epithelia with slight or moderate atypia (preneoplastic lesions) were seen at 2 weeks. After the 4th week, they produced tumor nodules in the tracheal transplants, whereas no tumor cells could be seen at the s.c. injection sites. The human derivation of the cells was confirmed by in situ hybridization using human-specific DNA probes. The intratracheal inoculation and xenotransplantation of human-derived cell lines offers a time-saving alternative to the s.c. inoculation assay for tumorigenicity and is at the same time a potentially valuable approach to studying preneoplastic and neoplastic progression with human cell subpopulations.

Animals↗
PubMed1987

Serum and urine concentrations of oral bromovinyldeoxyuridine in humans as monitored by a bioassay system based on varicella-zoster virus focus inhibition.

A simple and sensitive bioassay method for measuring (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) concentrations in human serum and urine has been established. This method is based on the inhibitory effect of BVDU on varicella-zoster virus (VZV) focus formation in vitro. The minimal concentration of BVDU that could be detected in serum by this method was 0.2 microgram/ml. Following a single oral administration of 250 mg BVDU, serum BVDU concentrations of 1.2-2.2 micrograms/ml were attained 1 hr later; at 5 and 7 hr, serum BVDU levels were below 0.2 microgram/ml. Upon repeated administration of 125 mg BVDU at 8 hr intervals, the serum BVDU concentrations reached 0.7-1.1 microgram/ml at 2 hr after the fourth administration. These concentrations are approximately 300-450-fold higher than the 50% inhibitory dose of BVDU for VZV in vitro. Urinary BVDU concentrations were on average 10 to 20 times higher than the serum BVDU concentrations.

Adult↗
PubMed1987

Effects of halothane, enflurane and pentobarbital on brain histamine dynamics in mice.

The effects of halothane, enflurane, ketamine and pentobarbital on brain histamine dynamics were examined in mice. Brain histamine and tele-methylhistamine, a predominant metabolite of brain histamine, were simultaneously measured by high-performance liquid chromatography with fluorescence detection. Anaesthesia with the four agents had no effect on brain histamine content. The tele-methylhistamine content significantly increased during 1 h and 2 h anaesthesia with halothane (0.051 mmol/l or 0.76 mol/l) and 2 h anaesthesia with enflurane (0.11 mol/l or 0.16 mol/l). Enflurane and pentobarbital significantly inhibited the histamine depletion induced by alpha-fluoromethylhistidine (50 mg/kg, intraperitoneally), a specific inhibitor of histidine decarboxylase, suggesting that these agents decrease the histamine turnover. However, halothane and ketamine were ineffective in this respect. These results emphasize that various anaesthetics have different influences on brain histamine dynamics. Since there have been findings suggesting that brain histaminergic systems are involved in physiological functions such as regulation of blood pressure, body temperature and hormone secretion, changes in the brain histamine turnover should be given due attention with regard to physiological changes during anaesthesia.

Anesthetics↗
PubMed1987

In vitro activity of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine against newly isolated clinical varicella-zoster virus strains.

The highly potent and selective anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] was found to inhibit in vitro the replication of a number of clinical varicella-zoster virus strains within the concentration range of 0.63-5.7 ng/ml. With a mean 50% inhibitory concentration of 1.8 ng/ml and selectivity index of 29000, (S)-HPMPA is one of the most potent and most selective varicella-zoster virus inhibitors discovered to date.

Adenine↗