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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 649 records · Page 36Linked to original sources

Promotion by ethanol of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of ethanol (EtOH) on the incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in Wistar rats. The animals received alternate-day i.p. injections of 2.5 ml kg-1 body weight of 20% EtOH in 0.9% NaCl solution after 20 weeks of oral treatment with MNNG. Prolonged administration of EtOH resulted in a significant increase in the incidence and number of gastric cancers of the glandular stomach in week 52. However, it had no influence on the histological types of the gastric cancers. Furthermore, it caused a significant increase in the labelling index of the epithelial cells of the antrum in week 52. These findings indicate that EtOH promotes gastric carcinogenesis, and that this effect may be related to its effect in increasing proliferation of the antral epithelial cells.

Adenocarcinoma↗

Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine, a selective anti-human immunodeficiency virus agent.

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of the replication of human immunodeficiency virus (HIV) in vitro in human T-lymphocyte MT-4, H9, and ATH8 cells. PMEA also inhibits Moloney murine sarcoma virus (Mo-MSV)-induced transformation of murine C3H embryo fibroblasts. Moreover, PMEA causes a dose-dependent suppression of tumor formation and associated mortality in mice inoculated with Mo-MSV. At a dose of 50 or 20 mg/kg per day PMEA effected a 90-100% protection of the mice against Mo-MSV-induced tumor formation and mortality. Even with a PMEA dose as low as 1 to 5 mg/kg per day, tumor formation was significantly delayed and the survival rate was significantly enhanced. In parallel experiments, azidothymidine exhibited a comparable inhibitory effect on Mo-MSV-induced tumor formation and associated death only at a 25-fold higher dose than PMEA. Because PMEA has stronger in vivo antiretrovirus potency and selectivity than azidothymidine and various other compounds currently being subjected to clinical trials, PMEA studies should be pursued to assess the potential of this compound in the treatment of acquired immunodeficiency syndrome (AIDS) and other retrovirus infections in humans.

Adenine↗

Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor.

The triphenylmethane derivative aurintricarboxylic acid (ATA), but not aurin, selectively prevented the binding of OKT4A/Leu-3a monoclonal antibody (mAb) and, to a lesser extent, OKT4 mAb to the CD4 cell receptor for human immunodeficiency virus type 1 (HIV-1). The effect was seen within 1 min at an ATA concentration of 10 microM in various T4+ cells (MT-4, U-937, peripheral blood lymphocytes, and monocytes). It was dose-dependent and reversible. ATA prevented the attachment of radiolabeled HIV-1 particles to MT-4 cells, which could be expected as the result of its specific binding to the HIV/CD4 receptor. Other HIV inhibitors such as suramin, fuchsin acid, azidothymidine, dextran sulfate, heparin, and pentosan polysulfate did not affect OKT4A/Leu-3a mAb binding to the CD4 receptor, although the sulfated polysaccharides suppressed HIV-1 adsorption to the cells at concentrations required for complete protection against HIV-1 cytopathogenicity. Thus, ATA is a selective marker molecule for the CD4 receptor. ATA also interfered with the staining of membrane-associated HIV-1 glycoprotein gp120 by a mAb against it. These unusual properties of a small molecule of nonimmunological origin may have important implications for the study of CD4/HIV/AIDS pathogenesis and possibly treatment.

Adsorption↗

Syncytium formation and destruction of bystander CD4+ cells cocultured with T cells persistently infected with human immunodeficiency virus as demonstrated by flow cytometry.

We have developed a flow cytometric method for demonstrating cell fusion between human immunodeficiency virus type 1 (HIV-1)- or HIV-2-infected HUT-78 cells and uninfected CD4-bearing MOLT-4 cells. Syncytium formation due to an interaction between the gp120 glycoprotein expressed on HIV-infected HUT-78 cells and the CD4 receptor present on MOLT-4 cells, resulted in an immediate decrease in the number of MOLT-4 cells; after a 24 h incubation period almost all MOLT-4 cells had disappeared from the culture. To show that the target MOLT-4 cells and not the aggressor HUT-78 cells were destroyed, specific monoclonal antibodies (MAbs) that reacted with antigens expressed on either MOLT-4 or HUT-78 cells were used. The formation of giant cells and the concomitant disappearance of MOLT-4 cells was blocked by MAbs specific for OKT4A and Leu3a, and, to a much lower level, by the MAbs specific of OKT4 and gp120. MAbs specific for OKT3, Leu2a, HLA-DR, Leu18 and LeuM3 did not prevent the disappearance of MOLT-4 cells. Sera from two AIDS patients containing antibodies to the HIV envelope glycoproteins did not protect MOLT-4 cells against the destructive effect of the HIV-infected HUT-78 cells. The fusion index, the percentage fusion inhibition and the 50% fusion inhibitory concentration of the MAbs can be accurately determined with the flow cytometric assay. The method can be readily implemented to evaluate any therapeutic treatment by examining its capacity to block cell-to-cell fusion, and hence destruction of the target bystander cells. Five anti-HIV compounds which have been previously shown to interfere with HIV binding to cells (namely pentosan polysulphate, heparin, suramin, aurintricarboxylic acid and Evans Blue) were further evaluated by this new method. With the exception of heparin, all of these compounds were found to inhibit cell-to-cell fusion and the concomitant destruction of the target bystander cells. Azidothymidine failed to inhibit fusion or bystander T cell destruction.

Antibodies, Monoclonal↗

Promotion by nialamide of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of nialamide, a monoamine oxidase inhibitor, on the incidence, number, and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in male Wistar rats. Rats were given subcutaneously 50 mg/kg body weight of nialamide in depot form every other day after 25 weeks of oral treatment with MNNG. Prolonged alternate-day administration of nialamide caused a significant increase in the incidence and number of gastric cancers of the glandular stomach in week 52. However, it did not affect the histology of the cancers. Nialamide also caused a significant increase in tissue norepinephrine concentrations in the gastric wall and in the labeling indices of the gastric mucosae. However, nialamide had no influence on serum gastrin levels in the fasting state and after re-feeding. These findings indicate that nialamide promotes gastric carcinogenesis and that this may be related to its effects in increasing norepinephrine in the gastric wall and stimulating proliferation of gastric epithelial cells.

Adenocarcinoma↗

[A case of septic shock due to pneumonia caused by Klebsiella pneumoniae].

A 51-year-old male, who had a history of excessive drinking and chronic hepatitis, was admitted to our hospital because of high fever and shock. Physical examinations, chest X-ray films and hemodynamic data revealed that he had progressed to septic shock due to pneumonia. Combination chemotherapy of latamoxef plus piperacillin was immediately started. After Klebsiella pneumoniae was isolated from bronchoalveolar lavage fluid, the antibiotics were changed to ceftizoxime plus amikacin. Furthermore human gamma globulin preparations and frozen fractional plasma were administered because of granulocytopenia and a decrease in complement. Gabexate mesylate, methylprednisolone (MP) and branched chain amino acids were given to prevent disseminated intravascular coagulation and/or multiple organ failure. With this intensive care, he recovered from shock and pneumonia. The effects of MP on the whole blood chemiluminescence (CL) were examined. Incubation of whole blood with 25, 50 or 100 micrograms/ml of MP for 10 to 60 minutes had no effects on the CL response. This indicates that MP does not affect the production of reactive oxygen species from phagocytic cells at concentrations comparable to those used in drug therapy.

Humans↗

Effects of 2(3)-tert-butyl-4-hydroxyanisole pretreatment on cefpiramide binding to mouse glutathione S-transferases.

Binding of cefpiramide (CPM) and other beta-lactam antimicrobial agents to 2(3)-tert-butyl-4-hydroxyanisole (BHA)-induced liver glutathione (GSH) S-transferases (EC 2.5.1.18) from CD-1 mice was studied. A marked induction of hepatic GSH S-transferase from mice fed BHA was observed. Gel chromatography of liver cytosol from mice fed BHA showed an increased binding of CPM, cefotetan and cefazolin to BHA-induced GSH S-transferases. The extent of their binding to GSH S-transferase seemed to be correlated with the extent of their excretion into the bile. Binding of CPM to the GSH S-transferase fraction was inhibited by both indocyanine green, which is known to bind liver GSH S-transferases intensively, and by cefoperazon, which is mainly excreted into the bile. This study suggests that GSH S-transferases are the main binding proteins of CPM in the liver cytosol fraction and play an important role as carrier proteins of CPM and some antimicrobial agents in mouse liver.

Animals↗

Three-dimensional analysis of morphogenesis induced by mating pheromone alpha factor in Saccharomyces cerevisiae.

Ultrastructural analyses of cytoplasmic changes in Saccharomyces cerevisiae X2180-1A (MATa) that had been treated with alpha factor were performed by using the freeze-substitution fixation method. After alpha factor treatment, cells exhibited a pointed projection, which is a unique pattern of oriented cell surface growth. The relationship between projection formation and intracellular organelles was examined using serial thin sections and computer-aided three-dimensional reconstructions. Using these analyses membrane vesicles and other organelles were detected, and studies on their dynamic structural reorganization became feasible. Production of membrane vesicles (average 65 nm in diameter) was induced upon exposure of the cells to alpha factor before projection emergence. The total number of membrane vesicles increased at the early stage and decreased at the late stage of projection formation. Three-dimensional analysis indicated that the vesicles were at first dispersed throughout the cell, then accumulated at the site where the projection formed. Morphological changes and multiplication of the Golgi body were seen during the process of projection formation. Other intracellular organelles (nucleus, vacuole, rough endoplasmic reticulum and mitochondria) were also rearranged, showing a polar organization of the cytoplasm during projection formation.

Mating Factor↗

Magnetic resonance imaging of intracavernous pathology.

To evaluate the usefulness of magnetic resonance (MR) imaging of intracavernous pathology, T1-weighted spin echo images of four vascular lesions and 10 neoplastic lesions with surgically confirmed cavernous sinus (CS) invasion were reviewed retrospectively. In one case of traumatic carotid-cavernous fistula (CCF) and one of dural arteriovenous malformation (AVM), the internal carotid artery (ICA) and rapid shunted flow were depicted as signal voids, and the relationship between the ICA and shunted flow was clearly shown. Normal venous flow appeared as a low-intensity area and was observed even in the presence of the CCF and dural AVM. In two cases of thrombosed aneurysms, the thrombosis was clearly demonstrated, along with patent arterial flow in one case; in the other case, however, it was impossible to differentiate patent arterial flow from calcification. The intensity of all neoplastic lesions was similar to that of the cerebral cortex. The relationship between the ICA and the tumors was clearly demonstrated. The visual pathways were also plainly shown unless they were involved, or markedly compressed, by tumor. CS invasion was strongly associated with four findings: 1) encasement of the ICA by the tumor; 2) marked displacement of the ICA; 3) absence of low intensity, which reflects normal venous flow, in the CS; and 4) extension of extrasellar tumors to the medial wall or of intrasellar tumors to the lateral wall. MR imaging was judged promising in the evaluation of intracavernous pathology.

Adenoma↗

Flow cytometric method to demonstrate whether anti-HIV-1 agents inhibit virion binding to T4+ cells.

The first step in the replicative cycle of human immunodeficiency virus type 1 (HIV-1) is binding of the virions to the cellular CD4 receptor. This process may be considered as an important target for chemotherapeutic agents against acquired immune deficiency syndrome (AIDS). A method has now been devised whereby virion binding to the cell membrane was visualized by an indirect immunofluorescence assay using human anti-HIV-1 serum, rabbit anti-human-IG-F(ab')2-fluorescein isothiocyanate, and flow cytometry. Heparin, dextran sulfate, and pentosan polysulfate suppressed HIV-1 binding to MT-4 cells at concentrations that protected the cells against HIV-1 cytopathogenicity. Dextran and dermatan sulfate, two compounds that are inactive against HIV-1, had no inhibitory effect on the binding of HIV-1 to the cells. The potent and selective HIV-1 inhibitor azidothymidine (AZT) did not affect virus binding to the cells, whereas suramin partially blocked HIV-1 binding to the cells at concentrations that fully protected MT-4 cells against destruction of HIV-1. Our immunofluorescence assay thus demonstrated that suramin not only acts as an inhibitor of reverse transcriptase but also interferes with virus-cell binding. Also, Evans blue, an anionic dye structurally related to suramin, partially inhibited HIV-1 attachment to the cells. The present method permits a quantitative determination of the inhibitory effect of anti-HIV-1 agents on virion-cell binding.

Antigens, Differentiation, T-Lymphocyte↗

Selective activity of several cholic acid derivatives against human immunodeficiency virus replication in vitro.

Several cholic acid derivatives such as taurolithocholic acid, lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate were shown to inhibit selectively the replication of human immunodeficiency virus type 1 (HIV-1) in vitro. These compounds completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 100 micrograms/ml, whereas no toxicity for the host cells was observed at 200 micrograms/ml. They also inhibited HIV-1 antigen expression in HIV-1-infected CEM cells. The bile acids (cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid) did not show any inhibitory effect on HIV-1 replication at concentrations that were not toxic to the host (MT-4) cells. From a structure-function analysis of a number of cholic acid derivatives, the presence of either a sulfonate (as in the tauro conjugates) or a sulfate group as well as the "litho" configuration appeared to be necessary for the expression of anti-HIV-1 activity. The active cholic acid derivatives did not directly inactivate the virus particles at the concentrations that were not toxic to the host cells. Lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate, but not taurolithocholic acid, partially inhibited virus adsorption to MT-4 cells. These three compounds were also inhibitory to the reverse transcriptase activity associated with HIV-1.

Adsorption↗

[Study on the effect of disodium cromoglycate (DSCG) on antigen induced IL-2 responsiveness].

We tested the effects of disodium cromoglycate (DSCG) on antigen-induced IL-2 responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma. Patient lymphocytes pretreated with 5 x 10(3) micrograms/ml DSCG for 24 or 48 hours failed to induce the responsiveness to IL-2 on stimulation with Dermatophagoides farinae (Df) or ovalbumin (OVA) antigen. DSCG-treated adherent cells were blocked to present the antigen to nonadherent responding cells for induction of IL-2 responsiveness. In contrast, DSCG-treated non-adherent cells, recombined with antigen-activated adherent cells, acquired IL-2 responsiveness. However, Con A-activated lymphocytes from the same patients were not affected by the same treatment. The results indicate that DSCG is capable of suppressing antigen-induced IL-2 responsiveness but not the response induced by mitogen such as Con A.

Antigens↗

Cell wall formation in regenerating protoplasts of Schizosaccharomyces pombe: study by high resolution, low voltage scanning electron microscopy.

The ultrastructure of regenerating cell wall in Schizosaccharomyces pombe protoplasts was studied with a high resolution, low voltage scanning electron microscope (LVSEM). In contrast to the transmission electron microscopy, the LVSEM images give three-dimensional information on the cell wall regeneration in yeast protoplasts. We found that, after only a few minutes of incubation, the protoplasts began to show protuberances in a unipolar manner, and a fibrilar network was formed asymmetrically which covered the whole surface of the protoplasts after 5 hr. The network consisted of microfibrils about 8 to 10 nm wide, forming flat and wavy bundles of various widths and lengths, up to about 200 nm wide and 1 micron long, mainly made of yeast glucan. Free ends of microfibrils were seldom found. Interfibrillar spaces were progressively filled with granular particles and finally the complete cell wall was formed after 12 hr. The fibrillar network was destroyed by the digestion with beta (1----3)-glucanase. When protoplasts were regenerating in the presence of aculeacin A, the fibrillar networks were not formed, resulting in incomplete cell wall formation. These observations suggest that beta-glucan is the main component of the microfibrils and that it plays an important role in the formation of the cell wall in S. pombe.

Antifungal Agents↗

[Application of transbronchial brushing for histological diagnosis of lung cancer].

In order to improve the preoperative diagnostic rate of lung cancer, histological examination was performed by transbronchial brushing in 35 cases, and diagnostic contribution of brushing specimen was compared with that of transbronchial forceps biopsy (TBFB). Histological structures were well preserved in the histology section of brushing specimens, especially in cases of small cell lung cancer. The positive rate of brushing histology was 46%, which was the same as that of TBFB. The total histological diagnostic rate was 66% with simultaneous examination of bronchial brushing and TBFB specimens. Consequently, the use of brushing specimens for histologic evaluation made an additional contribution to the correct positive histology diagnostic rate. Brushing histology is indicated for all types of lung cancer, because in most TBFB-negative cases, biopsies were performed from inappropriate sites of tumors or their materials wer crushed by forceps. It was suggested that concomitant application of brushing specimen for histology examination, contributed to more accurate preoperative histology diagnosis for lung cancer.

Adenocarcinoma↗

[In vitro detection of ovalbumin-specific IgA producing cells from lymphocytes of patients with hen-egg allergy].

We studied antigen-specific IgA production from the peripheral lymphocytes of children with hen-egg allergy by using the method of indirect plaque forming cell (PFC) assay. The number of OVA-specific IgA-PFC generated from the patient lymphocytes was low (6 +/- 3/7 X 10(4) non T cells) in comparison with age-matched normal children (112 +/- 18/7 X 10(4) non T cells). The numbers of OVA-specific IgG-PFC and IgM-PFC generated from the patient lymphocytes were not so different from those of the age-matched normal children. This indicates that the activity of OVA-specific IgA-antibody production was reduced in patients with hen-egg allergy.

Child, Preschool↗