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Biomedical subjects

M Muto

Publications and source records attributed to M Muto.

At least 109 records · Page 6Linked to original sources

Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis.

Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of gamma T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2+ (TL-2+) thymocytes. Limited numbers of TL-2+ cells from individual irradiated B10.Thy 1.1 mice were injected into B10.Thy 1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F;10C), t(1A;13D) or t(6A;XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after gamma T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after gamma TCR rearrangements.

Animals↗

Significance of antibodies to streptococcal M protein in psoriatic arthritis and their association with HLA-A*0207.

Psoriatic arthritis (PA) is an immune disease associated with HLA-A2 in the Japanese population. To investigate mechanisms the association between HLA-A2 and PA, we examined in vivo immune responsiveness to Streptococcus pyogenes. Recombinant M proteins for the subtype specific N-terminal half (AB region) and conserved C-terminal half (C region) were produced separately. IgG antibody level against each region was measured by ELISA in 31 PA patients, 88 patients with psoriasis vulgaris, 6 patients with rheumatoid arthritis and 77 healthy controls. We found that IgG antibody levels against the C region were markedly higher in the PA patient group than in the other disease groups or controls. Further, IgG antibody levels were higher in PA patients with spondylitis and polyarticular arthritis than in PA patients with rheumatoid-like arthritis and arthritis mutilans. In contrast, no significant difference in the IgG antibody levels against the AB region was observed among the tested groups. HLA-A2 DNA typing showed that HLA-A*0207 was associated with PA (RR = 17.6; pcorr < 0.01) and the IgG antibody responses to the C region correlated well with the presence of HLA-A*0207. These results suggest that streptococcal infection may be involved in the pathogenesis of PA by participating in the HLA-linked immune responsiveness.

Antibodies, Bacterial↗

Putative linkage between HLA class I polymorphism and the susceptibility to malignant melanoma.

Human leukocyte antigen (HLA) frequencies in 67 melanoma patients were compared to 120 controls in Japan. The frequency of HLA-B13 was increased in melanoma patients compared to controls and was particularly common in nodular melanoma HLA-B61 was decreased in melanoma patients. Almost 50% of acral lentiginous melanoma patients expressed HLA-B51 compared to 0% of nodular melanomas.

Asian People↗

Immune response to Streptococcus pyogenes and the susceptibility to psoriasis.

Monoclonal antibodies directed against type 12 Group A streptococcal cell wall antigens cross-react with nuclei and cytoplasm of cells from skin and synovium from controls, uninvolved skin of psoriatics and psoriatic plaques. Patients with psoriasis had high serum titres of antibody against the M12 (C-region) streptococcal antigen compared to controls. An abnormal immune response directed against a "self' antigen after initiation by Group A streptococcal infection may play an important role in the exacerbation or development of psoriasis.

Antibodies, Monoclonal↗

Cardiac rod body: hypertrophic Z-line in an aged pony.

Numerous rod bodies were found in a heart sample from a 33-year-old pony by a conventional electron-microscopic technique. The rod bodies were concentrated in localized areas of both atria and ventricles, without a specific pattern of distribution. The rods appear to have a typical crystalline-like structure which presumably contains actin backbone filaments and alpha-actinin as major protein constituents. Diminution, fragmentation, and disorganization of the myofibrils, random expansion of electron-dense materials, especially at the fasciae adherens of the intercalated disc, an increase of intercellular space, frequently associated with connective tissue elements, and accumulation of glycogen granules, lipofuscin, mitochondria, and nonviable organelles in the rod body-containing cells suggested that rod-containing myocytes are in a degenerating stage and that rod body formation occurs in atrophic cardiomyocytes rather than normal or hypertrophic cardiomyocytes in the aged pony heart.

Aging↗

Myocardial bridge muscle on left anterior descending coronary artery differs from subepicardial myocardium of the left ventricle in dogs.

The myocardial bridge (MB) is a muscle band found sporadically above the coronary artery (CA) in humans and certain animals such as the dog, cat and sheep. The purpose of our study was to compare the structure of the MB muscle with that of tissue from the subepicardial myocardium. The histological studies included toluidine blue staining of 1-micron-thick sections and Gomori's trichrome staining of canine cardiac samples. The MB muscle of the dog heart is characterized by a distinctive spatial arrangement, with individual fibers separated by substantial elements of intercellular connective tissue in cross-section. Longitudinally, the long, slender fibers are aligned continuously with intermediation of intercalated disks lying perpendicular to the long axis of the fibers. In other regions of the left ventricular subepicardial myocardium, each myocyte is tightly packed in transverse view. There is great variation in the thickness (0.11-2.24 mm, average 0.45 mm) of MBs and the distance (24-236 microns, average 103 microns) between MBs and the left anterior descending coronary artery (LAD) among the 13 affected dogs examined, with no apparent relationship between the occurrence of MBs and either age or sex. These results on MB alignment suggest that the MB muscle generates force along the long axis of the fiber orientation as skeletal muscle does, and with minimal constriction of the CA; if so, the function of MB myocytes may differ from that of common cardiac myocytes, as does the structure. Then, the long-supposed downward compressive force of MBs on the LAD would be minimal in most cases; however, when the MB produces a systolic narrowing of the LAD known as the milking effect, the degree of lateral compression and its influence should depend not only on the substantial size of the MB muscle but also on the distance between the MB muscle and LAD. The environment surrounding the LAD may be a crucial factor in determining whether the MB influences the induction of heart disorders or not.

Animals↗

Cytogenetic analysis of thymocytes during early stages after irradiation in mice with different susceptibilities to radiation-induced lymphomagenesis.

To investigate the relationship between radiation-induced chromosomal instability and lymphomagenesis, the incidences of chromosome aberrations and of cells with abnormal chromosome complements in the thymuses of B10. Thy 1.1 and STS/A strains which have shown marked differences in susceptibility to radiation-induced lymphomagenesis were compared at an early time (12-33 days) after whole-body X-irradiation (1.61 Gy X 4). Numerical and structural aberrations of chromosome in B10. Thy 1.1 mice were higher than those in STS/A mice. The average incidence of trisomy 15 was 37.5% (12/32 mice) from 12 days to 32 days after irradiation in B10. Thy 1.1 mice, whereas none was found (0/38 mice) in STS/A mice. Frequencies of aberrations in chromosomes 11, 12, 15 of the thymocytes from irradiated B10. Thy 1.1 mice were higher than those from irradiated STS/A mice, and especially, the most frequent translocations occurred in the E-F regions of chromosome 12. using B10. Thy 1 congenic mice, we found that in many cases (8/13), the chromosome aberrations detected in the thymocytes from B10. Thy 1.1 mice at an early time after irradiation could also be observed in the donor-type (Thy 1.1) lymphomas developed from recipient mice 4-5 months after intrathymic injection, suggesting that these chromosome aberrations have some role in lymphomagenesis. The difference of chromosome instability detected at an early time after irradiation might be due to genetic background with regard to genomic instability induced by radiation.

Animals↗

Mitral valve protrusion assessed by use of B-mode echocardiography in dogs with mitral regurgitation.

OBJECTIVE: To examine our hypothesis that changes of the mitral valve in dogs with mitral regurgitation lead to various degrees of protrusion of the cusp in individual dogs in systole. DESIGN: Assessing the mitral protrusion, using B-mode echocardiography in dogs with mitral regurgitation. ANIMALS: 33 dogs with chronic mitral regurgitation and 40 clinically normal dogs. PROCEDURE: The mitral valve was imaged in the right parasternal left ventricular long-axis view, and we measured the height (H) from the coaptation point or tip of the protruded cusp to the mitral annular plane. When the tip of the protruded cusp was located beyond the mitral annular plane extending into the left atrium, H was expressed as negative values. RESULTS: The H in clinically normal dogs was 3.7 +/- 0.8 mm. In dogs with mitral regurgitation, the mitral cusp protruded toward the left atrium to various degrees, and H was -0.7 +/- 1.9 mm (range, 2.9 to -5.0 mm). The 2 dogs in the latter group with the lowest H (-5.0 and -4.5 mm, respectively) presented typical mitral flail on B-mode images. The indices of left atrial and ventricular dimension (left atrial dimension/aortic dimension and left ventricular end-diastolic dimension/body weight, respectively) were significantly higher than those in the clinically normal dogs and were negatively correlated with H. CONCLUSION: The mitral valve in individual dogs with mitral regurgitation has different degrees of protrusion. The degree of protrusion might be related to the hemo-dynamic condition in mitral regurgitation.

Animals↗

Anti-tumor effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in seborrheic keratosis.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a drug with potent antiproliferative action on keratinocytes that have nuclear receptors for 1,25(OH)2D3. We investigated the effects of 1,25(OH)2D3 on widespread seborrheic keratoses in 51 patients with these tumors. The data indicated that resolution of these tumors was dependent on both tumor size and dose of 1,25(OH)2D3. Among 15 patients treated with a high dose (0.5 microgram/d) of oral 1,25(OH)2D3, the lesions of widespread seborrheic keratoses changed from brown-black papules to brownish papules with erythema and/or crust as early as 2 wk after the start of treatment. The tumors finally developed into an atrophic scar or brownish pigmented macule. Histologically, vacuolation of the spinous cells, vesicle formation, and liquefaction degeneration of the basaloid cells were observed. Numerous lymphocytes had infiltrated in the papillary dermis. Among 36 patients treated with a low dose (0.25 microgram/d) of 1,25(OH)2D3, brownish papules became pale to normal in color and reduced in size, without erythematous change. Histologically, acanthosis of the epidermis was reduced, but degenerative change of the tumor cells was not observed. These data suggest that oral therapy of 1,25(OH)2D3 is an acceptable method well suited to the removal of seborrheic keratoses, especially those that are predominantly small tumors.

Adult↗

A case of an intra-atrial tumor thrombus from hepatocellular carcinoma (HCC), first indicated by 67Ga-citrate scintigraphy.

We encountered a very rare case of an intra-atrial tumor thrombus from hepatocellular carcinoma (HCC). Conventional XCT and US gave evidence of HCC. In nuclear medicine studies performed incidentally, the first study with 99mTc-phytate liver scintigraphy showed 2 SOLs and evidence of chronic liver disease, and the second study with 67Ga-citrate scintigraphy demonstrated 2 hot lesions within the liver parenchyma, and also another unexpected hot area just above the left lobe of the liver, seemingly beyond the diaphragm. When echocardiography was performed, in addition to ECG, because the patient began to complain of dyspnea, an oblong mass lesion was detected within the right atrium. Reexamination with XCT and angiography clearly proved the existence of an intraatrial tumor thrombus. These results indicate the need for routine examination by echocardiography for HCC patients complaining of dyspnea.

Carcinoma, Hepatocellular↗

The characterization of the monoclonal antibody Th-10a, specific for a nuclear protein appearing in the S phase of the cell cycle in normal thymocytes and its unregulated expression in lymphoma cell lines.

A monoclonal antibody (Th-10a) specific for the nuclear protein appearing in the S phase of the cell cycle in normal mouse thymocytes was derived by immunizing Wistar rats with a murine thymic lymphoma (TIGN), and its isotype was rat IgG2a and had kappa light chain. Immunohistochemical staining of frozen sections of B10.Thy1.1 newborn thymus and embryonic intestine revealed that this monoclonal antibody reacted strongly with the nuclear proteins of subcortical thymocytes and the basal layer of the mucosa, where many cells were dividing, but not with that of the thymic medullary area. To evaluate the expression of the nuclear proteins during the cell cycle in detail, the results of an immunofluorescence analysis of the thymocytes from hydroxyurea-treated B10 mice using Th-10a monoclonal antibody were compared with those of DNA synthesis of these cells with the use of the FITC-conjugated anti-BrdUrd monoclonal antibody. The results indicated that the nuclear protein detected by Th-10a monoclonal antibody was highly expressed in the S phase of normal thymocytes, while the cells in G1, G2 and M phases exhibited a low level of the expression. Moreover, the variations in expression of the nuclear proteins in the thymocytes at different times after hydroxyurea treatment were observed to correspond with the frequency of DNA synthesizing cells. In contrast, the high level and unregulated expression of the nuclear protein detected by Th-10a monoclonal antibody was observed throughout the cell cycle of the mouse lymphoma cell lines examined. Since Th-10a monoclonal antibody does not react with the nuclear proteins derived from human, hamster or rat proliferating cells, this antibody may recognize a murine specific epitope of the nuclear protein. To further characterize the nuclear proteins, we extracted them from normal thymocytes or thymic lymphomas, and analysed them by immunoblotting or immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis. The nuclear protein(s) detected by Th-10a monoclonal antibody was mostly 95 kDa and also 83 kDa polypeptide. The results also indicated that the 95 kDa nuclear protein was phosphorylated in vivo.

Animals↗

Proximal paraconal interventricular myocardial bridge in dog: ultrastructural characterization.

The ultrastructure of the dog myocardial bridges (MB), named here the proximal paraconal interventricular-myocardial bridge (PPI-MB), was examined to determine if its structure is identical to that of ordinary cardiac muscle. This study is preparatory to the establishment of PPI-MB as a physical and physiological model system to examine the influence of MB on coronary flow in cardiac function. Five of 46 dog hearts examined possessed PPI-MB, the occurrence of which was independent of sex, age and breed. The dog PPI-MB was localized in a limited area in the proximal third of the paraconal interventricular groove. PPI-MB myocytes and myofibrils were arranged quite straight and smooth, with minimum branching. PPI-MB myocytes formed side-by-side cell junctions through the mediation of mitochondria. Connective tissue elements were involved in terminal cell adhesion to form the myomyous junction beside the intercalated disc. The excitation conductive system of sarcoplasmic reticulum-T tubule often showed a triad. Numerous nerve axons or nerve ending-like structures appeared. Many structural views deviated somewhat from common cardiac muscle structure. This paper represents the first detailed description of PPI-MB muscle.

Animals↗

Immunohistological reaction mechanism of anti-monosialoganglioside monoclonal antibody, MAb 202, showing predominant cytotoxicity for malignant melanoma.

Mouse monoclonal IgM antibody (MAb 202) can cause melanoma cell necrosis in vivo. We analysed its immune mechanism in three melanoma patients to whom MAb 202 was administered. After the MAb 202 administration, histopathological analysis showed necrosis of melanoma cells expressing only GM3 in two patients. Another patient carrying both GM3 and GD3 showed infiltration of lymphocytes within the tumor nest but no tumor cells or nest necrosis. Immunohistological examination using anti-mouse IgM antibody revealed MAb 202 bound on the surface of melanoma cells in two patients but not in the third (positive for both GM3 and GD3). In vitro, MAb 202 reacted with the melanoma cells of the same two patients, but not with any other tissues of these individuals. We found no reaction of MAb 202 to non-melanoma cells including normal melanocytes and glia cells. Our trials suggest, 1) MAb 202 reacts directly to monosialogangliosides on the melanoma cell surface and then leads to the cytotoxicity reaction, or 2) MAb 202 induces lymphocyte infiltration and possibly then promotes the secretion of some cytokines.

Adult↗