Muscle fiber atrophy and degeneration induced by experimental immobility and hindlimb suspension.
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Biomedical subjects
Publications and source records attributed to M Miyazawa.
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A retrospective study of 155 patients with submucosal gastric carcinoma compared the clinicopathologic features with mucosal and muscularis proprial gastric carcinoma. Fifty-seven percent of the patients presented with gastrointestinal symptoms, whereas 36.1% had been detected by mass screening. The incidence of curative resection, lymph node metastasis, and complications were 96.1, 20.6, and 14.8%, respectively. Two patients died of sepsis and pulmonary infarction 30 days post-operatively. Five patients died of recurrent gastric cancer 1-5 years postresection. The overall 5-year survival rate was 90.2%. Recurrence patterns, histologic type, lymph node metastasis, lymphatic and venous infiltration, and growth pattern were similar to those of muscularis proprial carcinoma rather than mucosal carcinoma. Therefore, curative gastrectomy with extended lymphadenectomy (D2) may be feasible for submucosal carcinoma of the stomach.
Malignant lymphoma of the skin is a type of extranodal lymphoma with a benign prognosis, in which the main organ involved is the skin. Some 80-90% of the cases in Japan show a T-cell phenotype. Mycosis fungoides and Sézary syndrome are common T-cell lymphomas of the skin. The tumor cells of mycosis fungoides, small and medium-sized cells with cerebriform nuclei, are detected in an epidermo-dermo junction. The tumor cells show CD3, CD4 and CLA, (cutaneous lymphocyte associated antigen) positivity. Various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA), and interferons, have been indicated for the good-risk group (stages I A, I B and II A). Electron-beam irradiation, various chemotherapy, such as low-dose etoposide, low-dose MTX and CPT-11 and deoxy coformycin (DCF) plus IFNs, have been indicated for intermediate-risk group (stage II B, III and IV A). BRMs plus low-dose etoposide, electron-beam irradiation and a multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, have been indicated for the high-risk group (stages IV A and IV B). Cutaneous B cell lymphoma (CBCL) can be diagnosed using a molecular biological assay. The tumor cells of CBCL do not express T-cell antigens such as CD2, CD3 and CD43 and show B-cell antigens such as sIg, CD19, CD20 and CD22. Electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). An effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, is required for patients with advanced stage CBCL (stages III and IV).
Molecular mimicry is defined as similar structures shared by products of dissimilar genes. This review article discusses a possible role of molecular mimicry in the production of autoantibodies. Antibodies reactive with products of bacterial and viral genes sometime cross-react with normal cellular proteins. Sera from patients with systemic autoimmune diseases show crossreactivity with some bacterial and/or viral gene products at a significant frequency. Identification of the structures of antigenic epitopes recognized by disease-associated autoantibodies by expression cloning of autoantigen molecules and gene fragment expression revealed the amino acid residues that are shared by autoantibody-defined epitopes and microbial proteins. The presence of amino acid sequences shared between microbial proteins and autoantigens and the detection of antibodies in patients' sera that bind to the crossreactive epitopes suggest that immune responses to bacterial and viral infections may initiate the production of autoantibodies. Receptor-mediated phagocytosis of autoantigen molecules by crossreactive B cells and subsequent antigen presentation to helper T cells may facilitate the production of autoantibodies reactive with separate epitopes, if the autoantigen complex contains multiple B-cell epitopes and a shared T helper cell epitope. Analyses of the fine specificity of T helper cell epitopes on Friend murine leukemia virus env gene products revealed unexpected heterogeneity and redundancy of T cell responses even to a single epitope. This heterogeneity in T cell responses might play a role in the activation of self-reactive T helper cells through molecular mimicry.
Friend murine retrovirus complex induces acute and fatal erythroleukemia when inoculated into immunocompetent adult mice. The development of leukemia after inoculation of Friend virus complex is controlled by several host genes. Some of the host genes influence immune responses against the viral antigens. Both CD4-positive T helper cells and CD8-positive cytotoxic T-lymphocytes specific for Friend viral antigens are required for spontaneous resistance against the virally induced leukemia. We have identified two separate T helper cell epitopes in the gp70 envelope glycoprotein encoded by the helper component of Friend virus complex. Immunization of mice with a synthetic peptide that represented one of the two T helper cell epitopes by a single injection with an adjuvant induced potent protective immunity against Friend virus-induced leukemia, even in the absence of CD8-positive T lymphocytes. In the immunized mice, virus-infected erythroid progenitor cells were rapidly eliminated from the spleen within two weeks after inoculation of the Friend virus. These data indicate unexpected importance and efficacy of CD4-positive T helper cells in immunity against retrovirus infections.
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A case of a 35-year-old woman with mature teratoma which was perforated into the pericardial cavity, was reported. She was admitted to our hospital for surgical treatment of anterior mediastinal tumor. On her 6th hospital day, she had high fever. A chest X-ray and UCG showed cardiomegaly and pericardial effusion. We diagnosed her as perforated teratoma into the pericardial cavity and the emergent operation was performed. The tumor adheeded to pericardium and a large quality of bloody effusion was found in the pericardial cavity. The tumor was removed with pericardium immediately. In this case, the mechanism of perforation was thought to be caused by infection and massive fluid influx into the cyst.
Several reports have shown that local anesthetics have a high affinity for muscarinic receptors and competitively inhibit the effects induced by cholinergic agents in various tissues, but there have been no reports on the muscarinic receptors of parietal cells. The effects of five doses of procaine (10(-8)M approximately 10(-4)M) and seven doses of oxethazaine (10(-8)M approximately 10(-5)M) on 14C-aminopyrine accumulation in isolated parietal cells of guinea pigs induced by 10(-4)M carbachol were studied. Procaine showed a potentiating effect with peak potentiation at a dose of 10(-5)M, while oxethazaine showed an inhibitory effect in a dose-dependent manner at doses higher than 3 x 10(-8)M and suppression below the control levels at doses higher than 3.5 x 10(-7)M. Procaine alone increased 14C-aminopyrine accumulation with peak response at a dose of 10(-5)M, while oxethazaine alone showed an inhibitory effect in a dose-dependent manner at doses higher than 3 x 10(-8)M. Oxethazaine shifted the carbachol dose-response curves to the right with suppression of maximal response. In conclusion, in parietal cells, procaine appears to display roughly similar action to carbachol through muscarinic receptors, while oxethazaine displays inhibitory action mainly by mechanisms other than inhibition at the muscarinic receptor site.
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Biotransformation of the 7,7'-epoxylignans, (+)-veraguensin, (+)-galbelgin and galgravin by Aspergillus niger has been investigated. These lignans were converted to their corresponding 4,4'-O-demethyl derivatives, (+)-verrucosin, (+)-fragransin A2 and nectandrin B.
The lpr and gld genes are thought to result in an incapacity for Fas-mediated apoptosis of T and B cells and the development of subsequent autoimmune disease. A newly established gld-congenic strain of mice, MRL/MpTn-gld/gld (MRL/gld), was found to develop vascular lesions involving arteritis and glomerulonephritis (GN), which were similar to those observed in the MRL/Mp-lpr/lpr (MRL/lpr) strain. However, comparative studies with a C3H/HeJ strain bearing lpr or gld revealed that these lesions developed only in mice with an MRL background. We were successful in transferring GN to normal MHC-compatible gld/gld and irradiated +/+ mice by bone marrow cells of MRL/gld mice, but were unsuccessful using those of C3H/gld mice. Transfer of arteritis, however, was only successful in mice with an MRL background. Nephritogenic monoclonal antibodies obtained from an MRL/lpr and an MRL/gld mouse were shown to be bone marrow-derived and rich in clonal diversity, and at least two of these were capable of causing glomerular injury by different mechanisms. Development of GN and systemic arteritis in MRL/lpr and MRL/gld mice will be dependent not only on their incapacity for Fas-mediated apoptosis but also on bone marrow cells and peripheral cells with intrinsic defects.
OBJECTIVE: The authors determined the effect of postoperative mediastinal irradiation in preventing local and pleural recurrence of thymoma. SUMMARY BACKGROUND DATA: The role of mediastinal irradiation after incomplete resection or biopsy of an invasive thymoma is well established. However, routine use of adjuvant mediastinal irradiation for patients with thymoma after complete resection remains controversial. METHODS: During the 19-year period from 1973 to 1992, operations were performed on 89 patients with thymoma. Of these 89 patients, 80 patients who underwent gross complete tumor resection including adjacent tissues that appeared to be invaded by tumor were selected for this study. The effects of postoperative mediastinal irradiation on the recurrence rate of thymoma were analyzed according to histologic type, clinical stage, and whether adhesions to or invasion of the pleura or pericardium were present. RESULTS: Recurrence of thymoma was observed in 13 of 80 (16.3%) patients. No recurrence was observed in 23 patients with noninvasive thymoma. In patients with invasive thymoma whose tumor was macroscopically adherent to the pleura but not microscopically invasive (p1), recurrence was observed in 4 of 11 patients (36.4%) when mediastinal irradiation was not performed, but in none of 10 patients who received mediastinal irradiation. However, in patients with microscopic pleural invasion (p2), a high recurrence rate was observed with mediastinal irradiation (40%, 6/15 patients) or without mediastinal irradiation (30%, 3/10 patients). Postoperative mediastinal irradiation for patients with microscopical invasion to pericardium (c2) did not decrease the recurrence rate. Analysis of the mode of recurrence showed that mediastinal irradiation may have been effective in preventing local recurrence, but it did not control the pleural dissemination that was observed in 12 of 13 recurrent cases. CONCLUSIONS: Mediastinal irradiation is not necessary for patients with noninvasive thymoma. In patients with invasive thymoma, postoperative mediastinal irradiation is effective in preventing recurrence in patients with p1 thymoma, but not in patients with p2 or c2 tumors. Further adjuvant therapy should be performed to supplement mediastinal irradiation in patients with p2 or c2 thymoma, even after complete resection.
To obtain monoclonal antibodies reactive with odontogenic but not other types of epithelium, mice were immunized with homogenates of fixed ameloblastoma tissues, and monoclonal antibodies Y4 and M11 were produced. Y4 reacted immunohistochemically with odontogenic epithelial components but not with those of squamous differentiation, while M11 reacted with odontogenic epithelial components and a part of keratotic epithelial tissues. Immunoglobulin isotypes of both antibodies were IgM as determined by Ouchterlony immunodiffusion and enzyme-linked immunosorbent assays. Western blotting revealed that the antigen recognized by Y4 had a molecular mass of approximately 66 kDa; however, the antigen reactive with M11 was not identified by Western blotting in spite of various attempts in changing reaction conditions. These antibodies may be beneficial to histological analyses of odontogenic tissues and their related lesions.
The biotransformation of oxazepam by Bifidobacterium bifidum was studied. The major metabolite was purified by chromatographic methods and found to be desmethyldiazepam using NMR, IR and other physicochemical data.
BACKGROUND: One of the features of Helicobacter pylori infection in the human stomach seems to be disordered gastric acid secretion. The effect of vacuolating toxin (VT) produced by H. pylori on gastric acid secretion was examined. METHODS: VT(+)(toxigenic) and VT(-)(nontoxigenic) strains of H. pylori were cultured in brucella broth. The culture supernatant was added to isolated parietal cells, and acid secretion and intracellular adenosine 3'5'-cyclic phosphate (cAMP) and Ca2+ levels were measured with the 14C-aminopyrine (14C-AP) method, with 125I radioimmunoassay (RIA), and with the fura-2 fluorescence method, respectively. RESULTS: In the VT(+) strain a considerable inhibitory effect on 14C-AP accumulation was observed. However, the VT(-) strain had no significant effect on intracellular c-AMP and Ca2+. CONCLUSIONS: The VT(+) strain of H. pylori has an inhibitory effect on gastric acid secretion, whereas the VT(-) strain does not. This inhibitory effect was not associated with the response of second messengers. It is speculated that VT produced by H. pylori has a direct action on H(+)-K+ adenosine triphosphatase in parietal cells.
A subset of gastric carcinoma carries Epstein-Barr virus (EBV). The immunophenotypic features of EBV-associated (EBV+) gastric carcinoma, which we have analyzed using 25 EBV+ cases, remain unclear. Frozen tissue samples were stained with antibodies to various immune cell markers. To evaluate the proliferative activity of CD8+ cells, we performed CD8/Ki-67 double staining on paraffin-embedded sections. The results were compared with those in EBV-negative (EBV-) gastric carcinomas. All EBV+ and EBV- gastric carcinoma cells expressed major histocompatibility complex class I, whereas major histocompatibility complex class II expression in tumor cells was more prominent in EBV+ cases. Intercellular adhesion molecule-1 and Fas/APO-1 expression was largely restricted to EBV+ cases. The lymphocytes that infiltrated EBV+ tumor nests were predominantly CD8+ T cells, many of which expressed perforin. Immunoelectron microscopy confirmed a close cell to cell contact between these CD8+ cells and carcinoma cells. CD8+ cells were CD11a+ and CD11b- by flow cytometry performed in one case. The labeling index of Ki-67, the proliferation-associated antigen, in CD8+ cells was 4 times higher in EBV+ cases than in EBV- cases. Our data suggest that these CD8+ cells, which bear a cytotoxic phenotype, are actively proliferating in close contact with EBV+ tumor cells and that the specificity of the CD8+ cells may be directed to EBV and/or cellular antigens expressed by the tumor. This is consistent with a generally favorable prognosis of EBV+ gastric carcinoma. Because the observed T-cell infiltration is insufficient to eradicate the tumor cells, certain immunosuppressive factors were speculated to allow the essentially immunogenic carcinoma cells to establish a macroscopic lesion.
We analyzed postoperative early complications of primary lung cancer in 321 cases during 1982 to 1993 in our hospital, and assessed the prevention and the treatment against these complications. In order of frequency the complications are, paroxymal supraventricular tachcarida (10.6%), atelectasis due to sputum (6.9%), pulmonary fistula for more than seven days (4.7%), hoarseness of voice due to recurrent nerve palsy (4.0%), chylothorax (2.5%), gastrointestinal tract complications (2.2%), reoperation due to massive bleeding (1.2%), wound dehiscence (0.9%), bronchial fistula (0.6%), rupture of ascending aorta (0.3%) and myocardial infarction (0.3%). The two cases of bronchial fistula after pneumonectomy, and one of myocardial infarction after lobectomy through the median approach died of early complications. The operative indication for primary lung cancer is extended to the patients with higher age and lower pulmonary function; so we should be careful for the pre and postoperative prevention and the rapid and appropriate treatment against these postoperative early complications.
A case of bronchial carcinoid was reported. A 39-year-old male was suffered from recurrent pneumonia. Bronchofiberscopy revealed a polipoid tumor nearly obstructing left superior bronchial trunk. CT scan showed a round tumor about 1 cm in diameter. Resection of the tumor was carried out by sleeve upper lobe loectomy. Histological diagnosis was typical carcinoid, and there was no lymph node matastasis. Postoperative course was uneventful. Granulation and stenosis were not observed at the part of anastomosis.