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Biomedical subjects

M Makino

Publications and source records attributed to M Makino.

At least 19 recordsLinked to original sources
PubMed1992

Impaired calcium mobilization in CD4+ and CD8+ T cells in a retrovirus-induced immunodeficiency syndrome, murine AIDS.

After infection with LP-BM5 murine leukemia viruses, susceptible strains of mice develop a severe and progressive immunodeficiency disease, termed murine AIDS (MAIDS), features of which include markedly impaired T cell response to mitogens or specific Ag stimulation and decreased production of IL-2. Since an elevation of intracellular calcium concentration resulting from binding of Ag to the TCR is associated with IL-2 production, T cells from mice either uninfected or infected with LP-BM5 murine leukemia viruses were examined by a calcium mobilization assay. Both CD4+ and CD8+ T cells from infected mice manifested impaired calcium mobilization responses upon in vitro stimulation with anti-CD3 mAb or Con A. The abnormalities appeared early after virus inoculation and showed no difference in time course between subsets of T cells. Frequencies of prestimulation calcium-positive cells among both CD4+ and CD8+ cells in mice with MAIDS were significantly higher than those for uninfected mice. These abnormalities were associated with presence of the MAIDS-inducing defective virus genome, but were not induced by infection of mice genetically resistant to development of MAIDS or with nonpathogenic helper murine leukemia virus, a virus component that induces high spontaneous proliferation of T cells, even in MAIDS-resistant mice.

Animals↗
PubMed1992

Analysis of role of CD8+ T cells in resistance to murine AIDS in A/J mice.

The mixture of retroviruses termed LP-BM5 murine leukemia virus (MuLV) contains a replication-defective genome (BM5def), the crucial element for induction of murine AIDS (MAIDS), as well as helper B-tropic ecotropic and mink cell focus-forming MuLV. Among Fv-1b mouse strains, C57BL mice are sensitive to infection by these viruses and to development of MAIDS, but A/J mice are highly resistant to all viral components and to induction of disease. Inasmuch as previous genetic studies indicated a major role in susceptibility for the H-2D locus within the MHC, the effect of CD8+ T cells in A/J resistance to MAIDS was analyzed by depletion of this subset using mAb. A/J mice treated with anti-CD8 mAb beginning soon after inoculation with LP-BM5 MuLV developed disease within 5 wk after virus inoculation. Histopathologic and flow cytometry alteration of tissues and cells from the mAb-treated mice were identical to those seen in virus-infected MAIDS-sensitive strains, and assays for MuLV demonstrated high-level expression of ecotropic MuLV and integration of BM5def. Parallel studies of A/J mice treated with anti-CD4 mAb after infection revealed enhanced expression of ecotropic MuLV but no integration of BM5def, and no signs of MAIDS were detected. These observations indicate that CD8+ T cells are critical in the resistance of A/J mice to LP-BM5 MuLV replication and development of disease and suggest that CD4+ T cells play a role in regulation of ecotropic virus replication.

Animals↗
PubMed1992

Increased therapeutic efficacy induced by tumor necrosis factor alpha combined with platinum complexes and whole-body hyperthermia in rats.

This study examined the effect of a trimodality therapy of the combination of recombinant human tumor necrosis factor alpha (TNF), whole-body hypertheria (WBH), and cis-diamminedichloroplatinum(II) (CDDP) or cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (CBDCA) on a fibrosarcoma and normal tissue in F344 rats. TNF (1 x 10(5) units/kg) increased the antitumor effect of both CDDP (1.5 mg/kg) + WBH (2 h at 41.5 degrees C) and CBDCA (30 mg/kg) + WBH. Tumor growth delay, which was 1.9 days for CDDP + WBH and 2.7 days for CBDCA + WBH (P less than 0.01 compared to control), was significantly increased to 2.9 days with TNF + CDDP + WBH and 5.4 days with TNF + CBDCA + WBH (P less than 0.05). WBH, TNF, CDDP or CBDCA alone, TNF + CDDP, TNF + CBDCA, or TNF + WBH had no significant effect on tumor growth. In contrast, administration of TNF did not enhance the CDDP- or CBDCA-mediated dose limiting normal tissue toxicity. CDDP + WBH-mediated acute renal injury and CBDCA + WBH-mediated acute myelosuppression, as determined by blood urea nitrogen and peripheral blood cell counts, respectively, were not increased with the addition of TNF to either dual modality therapy. Histopathologically, addition of TNF produced no significant alterations in the kidney and the bone marrow as compared to CDDP + WBH or CBDCA + WBH. These data show that TNF enhanced the platinum + WBH-mediated antitumor effect without increasing normal tissue toxicity, suggesting that TNF may increase the therapeutic efficacy of CDDP or CBDCA combined with WBH.

Animals↗
PubMed1992

CD4+ subset regulation in viral infection. Preferential activation of Th2 cells during progression of retrovirus-induced immunodeficiency in mice.

Progressive lymphoproliferation and increasingly severe immunodeficiency are prominent features of a syndrome, designated mouse AIDS, which develops in susceptible strains of mice infected with the mixture of murine leukemia viruses, termed LP-BM5. Development of splenomegaly and lymphadenopathy, caused primarily by increases in B cell immunoblasts, requires the presence of CD4+ T cells and is assumed to be mediated by lymphokines produced by these cells inasmuch as progression of disease is markedly inhibited by treatment of infected mice with cyclosporin A. Studies of spleen cells from infected mice revealed spontaneous production of cytokines (IFN-gamma, IL-2, IL-4, IL-5, and IL-10) characteristic of Th0 (or a mixture of Th1 and Th2) T helper cells at 1 wk after infection. At later times, IFN-gamma and IL-2, characteristic products of Th1 helper clones, were expressed poorly, either spontaneously or after stimulation of cells with Con A. In contrast, IL-4, IL-5, IL-6, and IL-10, cytokines typically synthesized by Th2 cells, were produced in response to Con A or spontaneously through 18 wk post-infection. Increased serum IgE levels and enhanced IL-10 mRNA expression were consistent with expression of Th2 cytokines at biologically significant levels in vivo. Selective depletion of T cell subsets before stimulation with Con A showed that CD4+ T cells were the primary source of IL-2, IL-4, IL-10, and, to a lesser extent, IFN-gamma in spleens and lymph nodes of normal or infected mice. These results suggest that persistent activation of CD4+ T cells with the lymphokine profile of Th2 helper clones is responsible for chronic B cell stimulation, down-regulation of Th1 cytokines, and impaired CD8+ T cell function in mouse AIDS. This provides the first demonstration that, like many parasitic infections, viruses encoding potent antigenic stimuli can markedly affect the balance of Th subset expression.

Animals↗
PubMed1992

Clinicopathological features of advanced gastric cancer detected by periodic mass screening.

We have attempted to clarify the clinicopathologic features of advanced gastric cancers that were detected in periodic mass screening by comparing them with those of cancers detected by an initial mass screening. The macroscopic type of the cancers detected by periodic mass screening included Borrmann's type 3 in 47% of cases but was an unclassifiable type because of its resemblance to early cancer in gross appearance in another 47% of cases. The predominant histologic type of the cancers was found to be poorly differentiated adenocarcinoma with scirrhous growth. From these results, advanced gastric cancers that resemble early cancers of the depressed type, in gross morphology, and which are histologically diagnosed as poorly differentiated scirrhous carcinoma, are assumed to be rapidly growing tumors. Therefore, some of the cases that have these characteristics may, in fact, represent early-phase scirrhous carcinoma, diffuse carcinoma classified as Borrmann's type 4, of the stomach.

Adenocarcinoma↗
PubMed1992

Central nervous system infection in a murine retrovirus-induced immunodeficiency syndrome.

Astrocyte-enriched primary glial cultures (AGC) from C57BL/6 mice were found to be highly susceptible to infection with the replication competent components of LP-BM5, consisting of the ecotropic and mink cell focus-inducing (MCF) helper murine leukemia viruses (MuLVs). The presence in infected AGC of defective LP-BM5 MuLV genome, a critical component for induction of the disease referred to as murine AIDS, was confirmed by Southern blot hybridization using a probe reactive with the p12 gag sequence of the 4.9 kb defective genome. Electron microscopic studies demonstrated C-type retrovirus particles in both astrocytes and microglial cells. In vivo studies demonstrated that the ecotropic MuLVs and the defective genome could be detected within AGC obtained form either 14-day-old mice following intraperitoneal inoculation or 7-day-old mice following intracranial inoculation. These findings suggest that: (1) the central nervous system (CNS) infection is present at an early stage in murine AIDS, (2) both astrocytes and microglial cells are possible CNS targets in which helper MuLVs replicate, and (3) these cells can harbor the defective genome that is a critical component for disease induction.

Animals↗
PubMed1992

Inhibitory influence of a new steroidal anti-androgen, TZP-4238, on prostatic hyperplasia in the beagle dog.

The effect of a synthetic steroidal anti-androgen, TZP-4238, on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Old male beagle dogs (5-9 years old) were divided into three experimental groups. Group 1 consisted of BPH controls. Groups 2 and 3 received TZP-4238 0.1 mg/kg/day and chlormadinone acetate (CMA) 0.3 mg/kg/day p.o., respectively, for 5 months. In group 1, glandular hyperplasia of the prostate was clearly detected. In contrast, TZP-4238 (Group 2) or CMA (Group 3) produced marked atrophy of the glandular epithelium. In addition, a histopathological study showed that TZP-4238 or CMA medication for 5 months exerted no effect on the testes and the pituitary luteinizing hormone (LH) cells. Therefore, it is suggested that TZP-4238 (0.1 mg/kg) or CMA (0.3 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes and pituitary LH cells. However, slightly decreased serum testosterone levels were found in TZP-4238-treated animals, due apparently to a direct and/or indirect effect on the testes. Thus, it is suggested that a marginal antigonadotrophic effect cannot be excluded. It is concluded that TZP-4238 is a potent anti-androgen for the treatment of spontaneous canine BPH, without any negative influence on the function of the testes and the pituitary LH cells.

Animals↗
PubMed1992

[Synthesis of new antirusty disinfectants. I].

New quaternary ammonium salts [N-alkyl-N-2-hydroxyethyl-N,N-dimethylammonium ethyl phosphate (21, 22), isopropyl phosphate (23), n-butyl phosphate (24) and N-alkyl-N-2-hydroxy-3-phenoxypropyl-N,N-dimethylammonium ethyl phosphate (25, 26), isopropyl phosphate (27), n-butyl phosphate (28) and bis(N-alkyl-N-2-hydroxy-3-phenoxypropyl-N,N-dimethylammonium) malate (29), fumarate (30), succinate (31), adipate (32) and N-alkyl-N-2-hydroxy-3-phenoxypropyl-N,N-dimethylammonium tartrate (33)] were synthesized by alkylation of the corresponding trialkylammonium salts with various epoxy compounds. The new quaternary ammonium salts showed much greater bactericidal activities and antirusting effects than those of benzalkonium chloride. They had also good compatibilities since no precipitate was observed if the solution of any anionic surface active agents were added to the solution of these new quaternary ammonium salts. This property is the same as that of amphoteric surface active agents.

Bacteria↗
PubMed1992

[A case of hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity].

A 68-year-old male patient with benign hypertension shows high levels of high density lipoprotein cholesterol (HDL-C) of 171 mg/dl. The serum total cholesterol was 240 mg/dl. An abnormal slow alpha band and polydisperse low density lipoprotein (LDL) bands were detected by agarose gel and polyacrylamide gel electrophoresis. The slow alpha band was considered as an apo E-rich HDL. A peak of large HDL particle and a peak of abnormal high-molecular-LDL particle were observed in the patient's serum by gel permeation high performance liquid chromatography. Cholesteryl ester transfer activity (CETA) of the patient's serum was completely deficient (0.0%/10 microliters/18 hr). From these results, it is strongly suggested that patient's hyper-HDL-cholesterolemia caused by a complete deficiency of CETA.

Aged↗
PubMed1992

[Clinical laboratory and expert system].

Computer-based expert systems are designed to incorporate the knowledge of a human expert such that the computer program will solve problems in a manner similar to the human expert. The systems can be applied fruitfully to many phases of the laboratory testing, including order entry, specimen collection, analysis, result verification, and reporting. Interpretive reporting by means of expert systems is useful for influencing physician's use of laboratory and they offer potential help for clinical decision making. Although much of the early work in the clinical laboratory involved stand-alone expert systems, approaches that integrate more closely with laboratory information system or hospital information system are being used. A short review on the technology of expert system with an emphasis on the roles played by clinical laboratory is made. A trial system dealing with thyroid diseases, based on interpretation of hormonal levels (TSH, Total and Free T3, T4), is described.

Clinical Laboratory Techniques↗
PubMed1991

Separation and characterization of sialic acid-containing salivary-type amylase from patients' sera with immunoglobulin A-type myeloma.

Isoamylases, with an abnormal anodic migration, were detected by an electrophoretic technique in the sera from two patients with immunoglobulin A-type myeloma. The abnormal isoamylase bands migrate towards the anode faster than the salivary isoamylase (S2) band and were stained more strongly than the S2 sub-band. The abnormal isoamylase could be separated from patients' sera by using size-exclusion high-performance liquid chromatography. The serum abnormal isoamylases were showed to be sialic acid residues containing amylase, after the study of treatment with neuraminidase (EC 3.2.1.18), and to be salivary-type amylase, after the study of reaction with human salivary monoclonal antibody. The abnormal bands were not detected in the saliva from one patient. The two patients had no detectable malignancies except myeloma. These findings strongly suggest that the sialic acid-containing salivary-type amylases were produced ectopically from myeloma cells. In this regard the ectopic amylase production by myeloma cells is discussed.

Aged↗
PubMed1991

Protective effect of cyclosporin A on immune abnormalities observed in the murine acquired immunodeficiency syndrome.

The murine leukemia viruses (MuLV) designated LP-BM5 induce an immunodeficiency disease in susceptible strains of mice with many features in common to human acquired immunodeficiency syndrome (AIDS), including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. The disease, termed murine AIDS (MAIDS), crucially depends on the presence of B cells and CD4+ T cells, suggesting that mutual activation of these two cell types is central in the pathogenesis of the immunodeficiency syndrome. Cyclosporin A (CsA), whose immunosuppressive effect is attributed mainly to inhibition of interleukin 2 and interferon-gamma expression, interferes in T-B cell interactions. Here we show that chronic treatment with CsA (40 or 60 mg/kg/day) before and after infection with LP-BM5 MuLV protects against the development of immunodeficiency disease as assessed by functional, serological and histopathological criteria. The protection was not complete, suggesting both CsA-sensitive and CsA-resistant components to the pathogenesis of this syndrome, and was found to be independent of ecotropic MuLV expression. These results underline immunopathological mechanisms in the progression of immune abnormalities in MAIDS that are susceptible to inhibition of CsA and may serve as an experimental basis for developing a treatment of the human disorder with immunomodulators.

Animals↗
PubMed1991

Prognostic significance of the number of metastatic lymph nodes in patients with gastric cancer.

To confirm the prognostic significance of the number of the metastatic lymph nodes (MLN) in cases of gastric cancer, the results of surgical treatment of 668 patients with primary gastric cancer were analyzed retrospectively. Five-year survival rates were calculated with reference to the number of MLN, namely, none (89.2%), one to three (77.4%), four to six (55.8%), and seven or more (36.2%). Furthermore, even when the cancer had invaded the serosa, 5-year survival was significantly more frequent in patients with one to three MLN (71.7%) than in those with four to six (35.5%) or more than six (31.5%) (P less than 0.01), and the 5-year survival was close to that of patients with no MLN (70.5%). Not only qualitative but also quantitative evaluation of lymph node metastasis is essential for estimating the prognosis of patients with gastric cancer.

Adult↗
PubMed1991

Effects of non-MHC loci on resistance to retrovirus-induced immunodeficiency in mice.

Mice of certain strains are highly sensitive to development of a severe immunodeficiency disease following inoculation as adults with LP-BM5 murine leukemia viruses (MuLV) whereas others are extremely resistant. These strain-dependent differences in response to infection have been shown to be genetically determined with resistance to disease being, in general, associated with homozygosity for Fv-1n and H-2 haplotypes a and d and sensitivity with homozygosity for Fv-1b and other H-2 haplotypes including b, s, and q. The Fv-1b, H-2r strain RIIIS/J (RIIIS) was found to be highly resistant to disease even though B10.RIII(71NS)/J (B10.RIII), also H-2r, was very sensitive, thus excluding a role for H-2 in the resistance of RIIIS. The characteristics of RIIIS resistance were evaluated in studies of infected (B10.RIII x RIIIS) F1, F2 and reciprocal backcross mice. Resistance to disease was shown to be semidominant and determined by more than one gene, although a preponderant influence of a single gene was suggested. Studies of segregating populations showed that resistance was not associated with or linked to polymorphisms of the V beta complex or genes in proximity to the Emv-2 locus on chromosome 8. However, there was almost complete concordance between absence of disease in infected mice and inhibition of ecotropic virus spread. These results demonstrate that genes other than Fv-1 or H-2 can profoundly influence the development of retrovirus-induced immunodeficiency and replication of ecotropic viruses.

Animals↗
PubMed1991

Magnetic resonance imaging of the brain in congenital rubella virus and cytomegalovirus infections.

Two children with congenital rubella virus and six with cytomegalovirus (CMV) infections, were examined by magnetic resonance (MR) and CT. Cranial MR imaging (MRI) with T2-weighted spin-echo (SE) and inversion recovery (IR) sequences demonstrated the following: periventricular hyperintensity (4), subcortical hyperintensity (5), delayed myelination (4), oligo/pachygyria (2), cerebellar hypoplasia (2). This study showed that the more-disabled children had more marked abnormal MRI findings. MRI was more effective in the detection of parenchymal lesion than was CT, although intraventricular calcification was better visualized with CT.

Brain↗