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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 685 records · Page 38Linked to original sources
PubMed1988

Fuchsin acid selectively inhibits human immunodeficiency virus (HIV) replication in vitro.

Fuchsin acid, an anionic dye, is a selective inhibitor of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in vitro. Its 50% effective dose for inhibition of HIV-1-induced cytopathogenicity in MT-4 cells and HIV-1 antigen expression in HUT-78 cells is 42 and 16 microM, respectively. These values are comparable to those of suramin, the first compound shown to be a selective inhibitor of HIV-1. However, fuchsin acid is less cytotoxic than suramin. The selectivity index of fuchsin acid, based on the ratio of the 50% cytotoxic dose to the 50% effective dose, is greater than 74 in MT-4 cells and greater than 39 in HUT-78 cells. Fuchsin acid is a much weaker inhibitor of HIV-1 reverse transcriptase than are suramin and aurintricarboxylic acid. Fuchsin acid does not interfere with the adsorption of HIV-1 particles to MT-4 cells even at concentrations that completely block HIV-1 replication in MT-4 cells. The mechanism of action of fuchsin acid remains subject of further study.

Animals↗
PubMed1988

Effects of bilateral and unilateral vagotomy on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

After administration of N-methyl-N'-nitro-N-nitrosoguanidine for 15 weeks, the effects of bilateral, anterior and posterior vagotomy on the incidence, number and location of gastric adenocarcinomas, gastric acid secretion and cell proliferation of the gastric mucosa were investigated in inbred Wistar rats. Bilateral or anterior vagotomy, but not posterior vagotomy, significantly increased the incidence and number of adenocarcinomas at experimental week 52. In sham-operated control rats and rats subjected to bilateral vagotomy, there was no significant difference between the incidence or number of gastric tumors in the anterior and posterior walls. After anterior and posterior vagal denervation, however, there were significantly more gastric cancers on the denervated side than on the other. Bilateral and unilateral vagotomy resulted in significantly reduced gastric acid secretion by experimental weeks 25 and 52. Bilateral vagotomy significantly increased the labelling indices of both the fundic and antral mucosa at both times, but did not cause any significant difference between those of the anterior and posterior wall. Anterior or posterior vagotomy resulted in a significant increase in the labelling indices of both the fundic and antral mucosa on the denervated side. These findings indicate that the vagal nerve exerts a trophic action on the gastric mucosa, and that the promoting effect of vagotomy on gastric carcinogenesis may be related to its effect in increasing proliferation of cells in the antral mucosa.

Animals↗
PubMed1988

Anti-retrovirus activity of 3'-fluoro- and 3'-azido-substituted pyrimidine 2',3'-dideoxynucleoside analogues.

The 3'-fluoro-and 3'-azido-substituted derivatives of 2',3'-dideoxythymidine (ddThd), 2',3'-dideoxyuridine (ddUrd), 2',3'-dideoxy-5-ethyluridine (ddEtUrd) and 2',3'-dideoxycytidine (ddCyd) have been synthesized and evaluated for their anti-retrovirus activity [against human immunodeficiency virus (HIV) and murine Moloney sarcoma virus (MSV)]. Based on their 50% effective doses the most potent inhibitors of HIV replication in human MT4 lymphocytes were: FddThd (0.001 microM), AzddThd (0.004 microM), FddUrd (0.04 microM) and AzddUrd (0.36 microM). Their selectivity indexes were 197, 5000, 500 and 677, respectively. In contrast, none of the 3'-substituted ddEtUrd derivatives had a marked antiviral effect. The 2',3'-dideoxynucleoside analogues showed poor, if any, substrate affinity for (bacterial) dThd phosphorylase. AzddThd and FddThd inhibited human dThd kinase to a much greater extent (Ki/Km: 0.66 and 3.4, respectively) than did AzddUrd or FddUrd (Ki/Km: 71 and 171, respectively). The Ki/Km values of FddCyd and AzddCyd for human dCyd kinase were about 60. Although phosphorylation is a prerequisite for the anti-retrovirus activity of the 2',3'-dideoxynucleoside derivatives, there is no close correlation between the anti-retrovirus potency of the 3'-fluoro- and 3'-azido-substituted ddUrd, ddThd, ddEtUrd and ddCyd derivatives and their affinity for dThd kinase or dCyd kinase.

Animals↗
PubMed1988

Inhibitory effect of prolonged administration of tetragastrin on experimentally induced intestinal metaplasia in Wistar rats.

The effect of tetragastrin on the induction of intestinal metaplasia by intragastric administration of 5% NaOH solution was investigated in Wistar rats. The prolonged administration of tetragastrin in depot form from 1 week after NaOH treatment resulted in a significant increase in basal gastric acid secretion and a significant reduction in the incidence and number of intestinal metaplasia in experiment week 35. A histologic examination showed goblet cell metaplasia and intestinal metaplasia without Paneth cells in rats treated only with olive oil. Only goblet cell metaplasia was found in rats treated with tetragastrin. These results show that the prolonged administration of tetragastrin to rats after NaOH treatment increases gastric acid secretion and suppresses the induction of intestinal metaplasia.

Animals↗
PubMed1988

Investigations on the anti-HIV activity of 2',3'-dideoxyadenosine analogues with modifications in either the pentose or purine moiety. Potent and selective anti-HIV activity of 2,6-diaminopurine 2',3'-dideoxyriboside.

Several 2',3'-dideoxyadenosine analogues with modifications in either the ribose or purine moiety were evaluated for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in MT-4 cell cultures. The 2',3'-dideoxyriboside of 2,6-diaminopurine (ddDAPR) inhibited HIV antigen expression and HIV-induced cytopathogenicity at a 50% effective dose of 2.4-3.8 microM, as compared to 3-6 microM for 2',3'-dideoxyadenosine (ddAdo), whereas 50% inhibition of MT-4 cell viability was noted only at a concentration of 477 and 889 microM, respectively. Both ddDAPR and ddAdo were only weakly inhibitory to the proliferation of a number of T-lymphoblast and T-lymphocyte cell lines, pointing to the selectivity of these compounds as anti-HIV agents. In contrast to ddAdo, ddDAPR was found to be a poor substrate for adenosine deaminase, which may be advantageous from a chemotherapeutic viewpoint. Substitution of an azido or fluoro group at the 2' and 3'-position of the ribose moiety in either "up" or "down" configurations resulted in a decrease of the anti-HIV potency and selectivity of ddAdo. In addition to ddDAPR other purine-modified ddAdo analogues, i.e. several pyrrolo[2,3-d]pyrimidine 2',3'-dideoxynucleosides, were investigated for their anti-HIV activity, but none of these derivatives proved as potent or selective as ddDAPR.

Adenosine Deaminase↗
PubMed1988

Inhibitory effect of prolonged administration of cysteamine on experimental carcinogenesis in rat stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine.

The effect of cysteamine (2-aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Prolonged administration of 25 or 50 mg per kg body weight of cysteamine after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach. Histological examination showed that the adenocarcinomas that did develop in rats treated with these 2 doses of cysteamine had high mucin-producing activity. Furthermore, treatment with cysteamine caused significant increases in serum gastrin level and gastric acid secretion, together with significant decreases in the antral mucosal pH and the labelling indices of pyloric and oxyntic gland mucosae and gastric cancer. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas and that its effect may be related to decreasing proliferation of cells in the gastric mucosae.

Adenocarcinoma↗
PubMed1988

Effect of cimetidine on inhibition by tetragastrin of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in depot form after treatment with N-methyl-N'-nitro-N-nitrosoguanidine resulted in a significant increase in gastric acid secretion, a significant decrease in the labeling index of the antral mucosa, and a significant decrease in the incidence of adenocarcinomas of the glandular stomach. Administration of cimetidine at 20 mg, but not 10 mg, per kg body weight with tetragastrin significantly reduced the gastric acid secretion induced by tetragastrin alone but did not influence the labeling index of the antral mucosa or the inhibitory effect of tetragastrin on gastric carcinogenesis. These findings indicate that gastric acid secretion has no influence on the development of gastric adenocarcinomas and that the inhibitory effect of tetragastrin on gastric carcinogenesis may be related to its effect in decreasing proliferation of cells in the antral mucosa.

Adenocarcinoma↗
PubMed1988

The in vitro and in vivo anti-retrovirus activity, and intracellular metabolism of 3'-azido-2',3'-dideoxythymidine and 2',3'-dideoxycytidine are highly dependent on the cell species.

Cell lines derived from different species show striking differences in their sensitivity to the cytostatic and anti-retrovirus activity, as well as the intracellular metabolism, of 3'-azido-2',3'-dideoxythymidine (AzddThd) and 2',3'-dideoxycytidine (ddCyd). AzddThd and ddCyd are considerably more cytostatic to human (i.e. Raji, Molt/4F, ATH8) cell lines than murine (i.e. L1210) cells. The intracellular levels of AzddThd 5'-triphosphate and ddCyd 5'-triphosphate formed do not seem related to the cytostatic effects achieved by these compounds. In human lymphoid (ATH8, Molt/4F) and caprine ovary (Tahr) cells AzddThd accumulates as its 5'-monophosphate (AzddTMP), whereas in murine leukemia (L1210) cells it is readily metabolized to the 5'-triphosphate (AzddTTP). The rapid conversion of AzddThd to AzddTTP in murine cells may explain why AzddThd has a pronounced activity against Moloney murine sarcoma virus (MSV)-induced transformation of murine C3H cells in vitro and MSV-induced tumor development in newborn NMRI mice in vivo. In contrast, ddCyd has not much activity in these murine assay systems, and this may seem related to the poor conversion of ddCyd to its 5'-triphosphate in murine cells. In human cells, however, ddCyd is more extensively phosphorylated to its 5'-triphosphate than in murine cells. When [3H]AzddThd and [3H]ddCyd were compared for their metabolism in ATH8 and Molt/4F cells, little [3H]AzddTTP was formed even after a 48-hr incubation period, whereas under the same conditions substantial levels of [3H]ddCTP built up gradually. Thus, much higher ddCTP than AzddTTP levels were achieved in human lymphoid cells, an observation that may be particularly relevant from a therapeutic viewpoint.

Animals↗
PubMed1988

Enhancement of blood-brain barrier permeability to sodium fluorescein by stimulation of mu opioid receptors in mice.

The effects of opioids on the permeability of the blood-brain barrier (BBB) were examined in mice with sodium fluorescein as an indicator of the permeability. The brain was perfused with saline 30 min after injection of sodium fluorescein (40 mg/kg, i.v.) and examined by fluorometry. Morphine hydrochloride (0.3-10 mg/kg, s.c.) markedly increased the brain level of sodium fluorescein dose-dependently without influencing the plasma level, when administered 20 min before sodium fluorescein injection. Intracerebroventricularly (i.c.v.) injected morphine hydrochloride (0.5 and 1.0 microgram) increased the brain sodium fluorescein level. Buprenorphine (0.1 and 0.5 mg/kg, s.c.) was also effective. However, pentazocine, ethylketazocine, U-50488H and SKF-10047 had no significant influence. The i.c.v. administration of [D-Ala2, MePhe4, Gly(ol)5]enkephalin (0.1 microgram) and [D-Ala2, D-Leu5]enkephalin (0.5 microgram) but not of [D-Thr2, Leu5]enkephalin-Thr increased the brain level of sodium fluorescein significantly. A small dose of naloxone (i.p.) significantly inhibited the effects of morphine, buprenorphine, [D-Ala2, MePhe4, Gly(ol)5]enkephalin and [D-Ala2, D-Leu5]enkephalin. ICI-174864 coadministered i.c.v. with [D-Ala2, D-Leu5]enkephalin was ineffective in antagonizing the effect of the latter. These findings suggest that the stimulation of mu opioid receptors results in an increase in BBB permeability to sodium fluorescein.

Animals↗
PubMed1988

A case of mediastinal germ cell tumor radically operated on after neoadjuvant chemotherapy-combined resection of the superior vena cava and reconstruction with expanded-PTFE graft.

A case of primary mediastinal germ cell tumor, which was radically treated with reconstruction of the superior vena cava (SVC) after neoadjuvant chemotherapy, is reported herein. This tumor, accompanied with SVC syndrome, was initially unresectably advanced and chemotherapy, using cis-dichlorodiamine-platinum, vindesine and bleomycin, was administered, resulting in a partial response with a 65 per cent tumor regression. The serum human chorionic gonadotropin, which originally had a high value, became reduced in parallel with the tumor regression to within the normal range. Complete tumor resection with reconstruction of the SVC using an expanded polytetrafluoroethylene (EPTFE) graft was successfully performed. The patient has now returned to productive employment and the graft is patent without any clinical symptoms of recurrence, 15 months post-operatively. Neoadjuvant chemotherapy is considered to be vitally important for the treatment of germ cell tumors originating in the anterior mediastinum and an EPTFE graft with external ring support seems to be acceptable as an artificial substitute for SVC replacement.

Adult↗
PubMed1988

Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds.

A rapid, sensitive and automated assay procedure was developed for the in vitro evaluation of anti-HIV agents. An HTLV-I transformed T4-cell line, MT-4, which was previously shown by Koyanagi et al. (1985) to be highly susceptible to, and permissive for, HIV infection, served as the target cell line. Inhibition of the HIV-induced cytopathic effect was used as the end point. The viability of both HIV- and mock-infected cells was assessed spectrophotometrically via the in situ reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The procedure was optimized as to make optimal use of multichannel pipettes, microprocessor-controlled dispensing and optical density reading. The absorbance ratio of the mock-infected control to the HIV-infected samples was about 20. This allowed an accurate determination of the 50% effective doses, as demonstrated for 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-dideoxycytidine (ddCyd), dextran sulfate and heparin. The technique significantly reduced labor time as compared to the trypan blue exclusion method, and permits the evaluation of large numbers of compounds for their anti-HIV activity.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro.

Several sulfated oligo- or polysaccharides such as pentosan polysulfate, fucoidan, dextran sulfate, heparin and iota-, kappa- and lambda-carrageenans proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. The most potent anti-HIV-1 activity was recorded for the oligosaccharide pentosan polysulfate, its 50% antiviral effective dose (ED50) being 0.19 microgram/ml in MT-4 cells. It inhibited HIV-1 antigen expression in HUT-78 cells at an ED50 of 0.02 microgram/ml, and complete inhibition of HIV-1 antigen expression was obtained at a concentration of 4.0 micrograms/ml. No toxicity for MT-4 cells was observed with pentosan polysulfate at a concentration of 2500 micrograms/ml. The anticoagulant activity of pentosan polysulfate was more than ten-fold lower than that of heparin (14.4 and 177 U/mg, respectively). In fact, pentosan polysulfate achieved its anti-HIV-1 activity at a concentration that is 370-fold below its anticoagulant threshold (1 U). Pentosan polysulfate inhibits virus adsorption to the cells, as was demonstrated by monitoring the association of radiolabeled HIV-1 virions with MT-4 cells.

Adsorption↗
PubMed1988

Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides.

A series of base-modified pyrimidine 3'-azido-2',3'-dideoxynucleosides and 3'-substituted purine and pyrimidine 2',3'-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AzddUrd), 3'-azido-2',3'-dideoxy-5-methylcytidine (AzddMeCyd), 3'-fluoro-ddUrd (FddUrd), 3'-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxyguanosine (AzddGuo), 3'-fluoro-ddGuo (FddGuo), and 3'-fluoro-2,6-diaminopurine 2',3'-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.

Animals↗
PubMed1988

Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.

The sulfated polysaccharides dextran sulfate and heparin have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Dextran sulfate (Mr 5000) and heparin (Mr 15,000) completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 25 micrograms/ml. Their 50% inhibitory concentrations were 9.1 micrograms/ml (dextran sulfate) and 7.0 micrograms/ml (heparin), respectively. No toxicity for the host cells was observed with these compounds at a concentration of 625 micrograms/ml. The anti-HIV-1 activity of heparins of various molecular weights correlated well with their anticoagulant activity. On the other hand, with dextran sulfates of low molecular weight (5000, 8000) a significant inhibitory effect on HIV-1 was achieved at a concentration that was not markedly inhibitory to the blood coagulation process. Dextran sulfate and heparin were not inhibitory to HIV-1 reverse transcriptase unless they were used at concentrations in excess of those that inhibited HIV-1 replication. They were highly effective against HIV-1 replication even when present only during the 2-hr virus adsorption period. Studies using radiolabeled HIV-1 virions indicated that dextran sulfate and heparin inhibit virus adsorption to the host cells.

Adsorption↗
PubMed1988

Resistance to serum-induced terminal differentiation in normal human tracheobronchial epithelial cells after in vivo exposure to 7,12-dimethylbenz[a]anthracene.

Normal human tracheobronchial epithelial cells (NHTBECs) from nine donors were used to repopulate de-epithelialized rat tracheas. After transplantation into nude mice and treatment with 7,12-dimethylbenz[a]anthracene (DMBA), the transplants were removed at 3, 4, 5 and 6 months. Epithelial cells from DMBA-treated tracheas were subculturable. Epithelial cells from most untreated tracheas were not subculturable. After treatment with 0.5, 1, 2, 4, 6 and 8% serum, cells exhibited increased subculturability after in vivo treatment with DMBA, did not terminally differentiate and were still proliferating even in medium containing 8% serum. Karyotypes from these cells showed considerable aneuploidy. Although these cells did not survive for more than 10 subcultures (42 weeks), this was considerably longer than the survival of control cells. Because of their longer survival, resistance to serum-induced terminal differentiation and chromosome alterations, they were considered to be phenotypically altered or partially transformed cells produced by in vivo treatment of human cells with a chemical carcinogen.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus.

Several sulfated polysaccharides (dextran sulfate, pentosan polysulfate, fucoidan, and carrageenans) proved to be potent inhibitors for herpes simplex virus, human cytomegalovirus, vesicular stomatitis virus, Sindbis virus, and human immunodeficiency virus. They were moderately inhibitory to vaccinia virus but not inhibitory to adenovirus, coxsackievirus, poliovirus, parainfluenza virus, and reovirus. These results indicate that, with the exception of parainfluenza virus, enveloped viruses are specifically susceptible to the inhibitory activity of sulfated polysaccharides.

Carrageenan↗