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Biomedical subjects

M Miyauchi

Publications and source records attributed to M Miyauchi.

At least 127 records · Page 7Linked to original sources

Genetic instability of human cells with DNA related to human retrovirus.

To elucidate the role of HTLV-I in human neoplasia, DNA was extracted from tumor tissues, cultured cells, and/or sera from 20 HTLV-I seropositive and from 10 seronegative cancer patients, subjected to PCR-PAGE, and analyzed by Southern hybridization. HTLV-I related sequences were detected in tumors of the seropositives with different types of cancer. In the seronegatives, gag related sequences were detected in some tumors, whereas LTR related sequences were detected in only uterus carcinoma and tax related sequences in none of tumors examined. These sequences were detected in tumor cells as well as lymphoid cells by in situ hybridization. Some of these sequences were also detected in cultured fibroblasts derived from ATL patients. Cultured normal human lymphocytes grew continuously in conditioned media following HTLV-I infection, and transformed on exposure to carcinogens. Chromosome changes in transformed cells appeared clustering to chromosomes abnormalized on HTLV-I infection. The frequency of abnormal chromosomes in lymphocytes was significantly higher in the seropositives and in their family members than in seronegative normal donors. The frequency increased with advancement of host age in the seropositives but not in the seronegatives. These findings indicate that some individuals carry HTLV-I related sequences that may be derepressed by host aging and resulted in increasing genetic instability of host cells rendering them increasingly susceptible to carcinogens.

Adult↗

Suppression of retroviral tumors in hosts immune to viral oncogene product.

Feline sarcoma virus of Snyder-Theilen strain (ST-FeSV) induces sarcomas in Wistar/Ma rats following neonatal virus injection. Induced tumors express the viral oncogene product (P85) and elicit in hosts the specific serum anti-P85 antibody detectable by Western blot analysis. Syngeneic adult female rats were immunized with an ST-FeSV induced sarcoma that was 100% transplantable to syngeneic adult rats. Newborns from immunized rats (vaccinated rats) were found to carry anti-P85 in their sera at birth. Following neonatal injection of the virus to vaccinated and non-vaccinated control rats, tumor incidence was found to be lower and survival time significantly longer in vaccinated rats than in controls (p < 0.01). A nonapeptide known to be thymic hormone (FTS) showed suppressive effects on tumor development. These results indicate that tumors caused by perinatal retrovirus infection may be suppressed by efficient elicitation of cell-mediated immune response against the product of oncogene of the causative virus.

Amino Acid Sequence↗

[Assessment of social disability of patients suffering from chronic mental illness with the role play test].

UNLABELLED: Among the chronic mentally ill patients, disabilities invade most parts of their social functioning, and influences their long term course profoundly. It is important clinical issue to improve disability. Social skills training is assumed to be effective method to improve disability, and it has been disseminated over Japan recently. The assessment system to evaluate disabilities objectively at the viewpoint of social skills must be required to verify effects of social skills training, and to develop further effective therapeutic method. A role play test is the assessment tool for social skills through role plays under specific social conditions. It was reported to be useful as the method of functional assessment before treatment, and as the tool to evaluate effects of treatment to improve disability. PURPOSE: We created the Role Play Test (RPT) which was adapted to Japanese cultural background, and we tried to verify feasibility, reliability, and validity of the RPT. SUBJECTS: Thirty out-patients attending in the Day Hospital attached to Tokyo University Hospital. Twenty-six were schizophrenia, and 4 were other diagnoses. METHOD: Subjects were assessed with the RPT, BPRS, SANS, four rating scales for social functioning, and self-efficacy rating scale. The RPT was designed to assess components of social skills--social perception, role play behavior, and self-efficacy. Role play behaviors were recorded with video tapes for analysis of interrater reliability. The RPT is consisted of 12 scenes to evaluate social skills which are required in daily life. Statistical analyses were done with SAS (Statistical Analysis System). RESULTS: (1) The RPT was presumed to be feasible clinically, because the RPT could be practiced easily and responsibilities of both subjects and testers were not so much. (2) Interrater reliabilities assessed with ANOVA-ICC on 12 items was sufficiently high except one item. (3) Construct validity was certified through factor analysis, and criterion-related validity was certified through correlation analysis with other rating scales of social functioning. (4) Individual profile of the RPT should be useful instrument for functional analysis before social skills training. We also discussed on some hypotheses on the causal relationship between positive and negative symptoms and social skills. The RPT could be used as a tool to research causes of disabilities, and to evaluate improvement of social functioning after psycho-social intervention including social skills training, because the RPT can assess social skills quantitatively according to the cognitive-behavioral model.

Adolescent↗

Structure of the alpha subunit of F1-ATPase probed by limited proteolysis.

The structure of the isolated alpha subunit of F1-ATPase from the thermophilic Bacillus strain PS3 was probed using limited proteolysis by four different proteases, and the following results were obtained. 1) Distribution of 21 protease-cleaved sites is similar to that of the beta subunit of F1-ATPase (Tozawa, K., Odaka, M., Date, T., and Yoshida, M. (1992) J. Biol. Chem. 267, 16484-16490), thus providing experimental evidence for similar folding topology of the two subunits, and the locations of 11 water-exposed loop regions in the tertiary structure are predicted. 2) Most proteolytic peptides remain associated to maintain the gross structure of the alpha subunit and can reassociate each other after denaturing urea treatment. 3) However, the carboxyl-terminal peptides comprising approximately 80 residues (C1 peptides) are released from other peptide(s) during proteolysis, and those comprising approximately 105 residues (C2 peptides) are released during native polyacrylamide gel electrophoresis after proteolysis. 4) Inclusion of Mg-ATP in the native electrophoretic system prevents the release of the C2 peptide. Addition of Mg-ATP to the proteolysis mixtures results in an increase of the C2 peptide population and a decrease of the C1 peptide population. Thus, Mg-ATP induces a conformational change at the regions of C1 and C2 peptides of the alpha subunit. 5) Except for the trypsin-treated one, protease-treated alpha subunits are reconstitutable with the native beta subunit into the form of alpha 3 beta 3 complexes, which show significantly higher ATPase activities than the intact alpha 3 beta 3 complex. This activation is attributable to the cleavage of a peptide bond that produces C2 peptides. The carboxyl-terminal region of the alpha subunit is likely to be involved in the regulation of ATPase activity in F1-ATPase.

Adenosine Triphosphate↗

Proliferative activity of salivary gland pleomorphic adenomas and myoepitheliomas as evaluated by the proliferating cell nuclear antigen (PCNA) labeling index (LI).

Thirteen examples of pleomorphic adenoma (PA) and 4 of myoepithelioma (Me, 2 plasmacytoid cell type, 2 mixed cell type) were examined with respect to their proliferative activity on the basis of proliferating cell nuclear antigen (PCNA) immunohistochemistry. In PA, PCNA labeling index (LI) in tubular/trabecular/solid areas was significantly higher than that in myxomatous or chondroid areas. Although the mean value of LI in PA and Me was not statistically different (PA; 3.02 +/- 1.03%, Me; 3.19 +/- 1.76%), the Me of mixed cell type composed of epithelial, spindle or clear neoplastic myoepithelial cells had significantly higher LI, indicating the possibility of more rapid growth than PA. The small difference in the mean value of PCNA LI between PA and the mixed cell type of Me, however, suggests that enucleation with a margin of normal uninvolved tissue remains the recommended treatment for Me, as well as for PA.

Adenoma, Pleomorphic↗

Non-calcifying Pindborg tumor with Langerhans cells.

A rare case of calcifying epithelial odontogenic tumor (CEOT) devoid of calcification is reported with histochemical, immunohistochemical and electron microscopic studies. The tumor occurred intraosseously in the left maxillary canine and premolar region of a 58-year-old man. The tumor chiefly consisted of scattered small islands of epithelial cells in an abundant fibro-myxoid connective tissue stroma. Among the nests, there were many spherical bodies of eosinophilic substance for which non-AA amyloid and non-keratin or basal lamina-like natures were demonstrated histochemically and immunohistochemically. In some nests, there were a few, occasionally several, cells positive for S-100 protein. Ultrastructurally, Langerhans cells with indented nuclei and Birbeck's granules were seen among tumor cells. The prognostic significance of the paucity of calcification and the presence of Langerhans cells in CEOT of which this is only the second description is discussed.

Calcinosis↗

FR901459, a novel immunosuppressant isolated from Stachybotrys chartarum No. 19392. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological activities.

FR901459, a novel immunosuppressant, has been isolated from the fermentation broth of Stachybotrys chartarum No. 19392. The molecular formula of FR901459 was determined as C62H111N11O13. FR901459 was found to be a member of the cyclosporin family. However, it is structurally distinct from any other cyclosporins discovered so far, in that Leu is present at position 5 instead of Val. FR901459 was capable of prolonging the survival time of skin allografts in rats with one third the potency of cyclosporin A.

Amino Acid Sequence↗

Adjuvant effects of antineoplastic prostaglandins to cisplatin in nude mice bearing human ovarian cancer cells.

Effects of antineoplastic prostaglandins (PG) on human ovarian cancer cell growth were examined by using HR cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. With regard to inhibition of cancer cell proliferation in vitro, the effects of delta 7-PGA1 was most marked, followed by that of delta 12-PGJ2, PGJ2 and PGD2. When antineoplastic prostaglandins were administered to nude mice bearing HR cells, tumor growth in groups treated with PGJ2 and delta 12-PGJ2 alone was significantly inhibited 63 days after tumor inoculation, compared to that in an untreated group. Consequently, a significant prolongation of median survival was obtained with delta 12-PGJ2, compared to that in untreated groups and in groups with cisplatin alone. In addition, when prostaglandins were administered together with cisplatin, adjuvant inhibitory effects on the tumor growth were obtained 35, 56 and 63 days after tumor inoculation. Subsequently a significant prolongation of median survival was observed when cisplatin was combined with PGD2 or delta 7-PGA1, compared to the results in groups treated with PGD2 alone, delta 7-PGA1 alone or cisplatin alone. Combination of PGJ2 or delta 12-PGJ2 and cisplatin resulted in a significant decrease of hematocrit and body weight 63 days after tumor inoculation, suggesting a deterioration of the median survival. These results suggest that combination of PGD2 or delta 7-PGA1 with cisplatin may be of clinical use for ovarian cancer resistant to cisplatin.

Animals↗

Enhanced collagen phagocytosis by rat molar periodontal fibroblasts after topical application of lipopolysaccharide--ultrastructural observations and morphometric analysis.

To investigate the effect of lipopolysaccharide (LPS) on phagocytic activity of collagen fibrils by periodontal fibroblasts, we studied rat molar gingival connective tissue and periodontal ligament under light and electron microscopy after topical application of LPS (5 mg/ml in physiological salt solution (PS)) on the gingival sulcus. Phagocytic activity of collagen fibrils by fibroblasts was evaluated by counting the number of collagen-containing vacuoles inside fibroblasts that were present within a defined area (1200 microns2). Values obtained from fibroblasts in the subepithelial connective tissue, the region near the alveolar crest, and the middle region of periodontal tissue were compared. Periodontal ligament fibroblasts showed increased phagocytosis of the collagen fibrils from 3 hours to 1 day after topical LPS application, but no differences were observed in the gingival tissue. The intracytoplasmic vacuoles containing collagen fibrils were of various sizes and shapes, showing positive for acid phosphatase and/or alkaline phosphatase reaction. Collagen phagocytic activity of the fibroblasts in the middle region of the periodontal ligament also increased after PS treatment. However, this was significantly less than that observed in LPS-treated animals (p less than 0.01). This study indicates that LPS may enhance the degradation of collagen by stimulating the phagocytic activity of the periodontal ligament fibroblasts.

Animals↗

Effect of exogenously applied prostaglandin E2 on alveolar bone loss--histometric analysis.

The effect of prostaglandin E2 (PGE2) on alveolar bone resorption was examined in 8-week old Wistar rats by histometric analysis. One mg/ml PGE2 topically applied to gingival sulcus induced a marked increase in osteoclasts. The number of osteoclasts increased progressively and reached a maximum at 12 hours. Ultrastructurally, these osteoclasts were in active form with well developed ruffled borders and clear zones. The changes in numbers of osteoclasts after application of various concentrations of PGE2 were dose-dependent (0.001 to 1.0 mg/ml), but higher concentrations of PGE2 (2 mg/ml) were less effective. In addition, the number of osteoclasts in groups treated with both PGE2 and endotoxin was higher than those that received PGE2 only. These results indicate that bone resorption caused by PGE2 depends on activation and increase of osteoclasts, and suggests that endogenous PGE2 production by host cells stimulated by plaque-associated bacterial endotoxin may be an important pathogenetic factor in periodontal disease.

Alveolar Bone Loss↗

[Event-related potential in patients with diabetes mellitus].

The event-related potential (ERP) was recorded for 24 patients with diabetes mellitus (age 67.5 +/- 8.5 years, mean +/- SD) and 28 healthy controls (age 61.0 +/- 10.6 years) to elucidate the involvement of the central nervous system (CNS) in diabetes mellitus. ERP was recorded during auditory discriminative tasks. The latencies of N100, P200, N200 and P300 from the Pz region were measured. Patients with diabetes mellitus showed significant prolongation of N200 and P300 latencies compared with the normal subjects, while no significant differences in N100 and P200 latencies were found between the two groups. In six of 24 patients, the P300 latency delayed beyond the 2SD of the appropriate age-related value estimated from the normal regression line. The delay of the P300 latency was not related to either the duration of illness, therapeutic methods, or metabolic control. From the present results, it would appear that higher brain function is impaired even in diabetic patients not manifesting overt CNS signs and symptoms.

Acoustic Stimulation↗

Human T-cell leukemia virus type I as agent inducing genetic changes in infected human lymphocytes.

Sera and DNA samples, including cord blood, were examined from six members of a three-generation family suspected of being carriers of HTLV-I. Serum antibodies to HTLV-I were detected by Western blot analysis more clearly in adults than in children. DNA sequences related to HTLV-I-gag and -tax, but not -pol genes were detected more clearly in specific PCR products of DNA of adults than those of children, and of the cord blood by Southern hybridization analysis. HTLV-I-related DNA sequences were also detected in some HTLV-I-seropositive as well as seronegative patients with T-cell dyscrasia and with other diseases, including carcinoma. Frequencies of chromosome abnormalities were found to be significantly higher in lymphocytes of HTLV-I-seropositive persons than in those of HTLV-I-seronegative persons. Immortalization of cultured lymphocytes following infection with HTLV-I was found to be accompanied by chromosome and gene rearrangements. Transformation of these cells following treatment with carcinogens was found to be accompanied by additional chromosome rearrangements. These results suggest that some persons may be born with HTLV-I-related sequences that are repressed in childhood. Repeated expression of their products may result not only in the host antibody response but also in increased chromosomal instability and in increased risk for further genetic changes of carrier cells when exposed to environmental carcinogens.

Adolescent↗

Antitumor effect of Nocardia rubra cell wall skeleton on syngeneically transplanted P388 tumors.

The antitumor activity of the immunomodulator, Nocardia rubra cell wall skeleton (N-CWS), was investigated using syngeneically transplanted P388 leukemia cells in a solid form. The s.c. growth of P388 tumors in DBA/2 mice was significantly suppressed by systemically administered N-CWS, and the effect was dose dependent. The antitumor effect of N-CWS was partially but significantly abrogated in splenectomized mice but not in T-cell or natural killer cell-deficient mice. Although spleen cells from mice treated with 1600 micrograms N-CWS contained no cytolytic activity, they exerted a significant cytostatic effect on P388 cell growth both in vitro and in vivo. Splenic cytostatic activity did not reside in T- or natural killer cells, but in plastic adherent cell population, macrophages. The response to N-CWS immunotherapy appeared to be associated with the number of macrophages infiltrating into the tumor lesions, and this was confirmed by histological analysis showing that P388 tumors from N-CWS-treated mice were intensively and dominantly infiltrated by macrophages. Furthermore, these were shown to be strongly tumor necrosis factor-positive by immunohistochemical analysis. These findings indicate that macrophages are the main effector cells playing a critical role in the suppression of P388 tumor growth in DBA/2 mice, and that tumor necrosis factor produced by these cells may be involved in the macrophage-mediated cytostatic effect induced by N-CWS. The fact that N-CWS suppressed the growth of weakly immunogenic P388 cells in syngeneic DBA/2 mice even when it was systemically injected would support the clinical potential of this agent.

Adjuvants, Immunologic↗

Spindle cell squamous carcinoma of the oral region. An immunohistochemical and ultrastructural study on the histogenesis and differential diagnosis with a clinicopathological analysis of six cases.

Six cases of spindle cell squamous carcinoma (SCSC) of the oral cavity were studied clinicopathologically, immunohistochemically and ultrastructurally to summarize the clinicopathological features of this rare neoplasm and to discuss the debatable histogenesis of the sarcomatoid component and the differential diagnosis of SCSC. The mean age of the patients was 72 years and the female to male ratio was 1:2. Four of them had a history of irradiation for pre-existing squamous cell carcinoma. One patient died of SCSC. While clinical and histological prognostic factors of SCSC could not be determined, it was shown that radical surgery resulted in good prognosis. The epithelial nature of the sarcomatoid component of SCSC was clearly revealed by a combination of immunohistochemical staining for keratins and electron microscopic demonstration of tonofilament-like filaments and/or desmosome-like structures. Together with electron microscopic evaluation of the tumour cells, immunohistochemical characterization of tumour cells using antibodies to keratin, vimentin, glial fibrillary acidic protein and S-100 protein is very helpful in differentiating SCSC from true spindle cell sarcoma, melanoma and malignant myoepithelioma. In the immunohistochemical differential diagnosis of SCSC, it is important to remember that SCSC should not be ruled out of the differential diagnosis by a positive reaction for vimentin in sarcomatoid tumour cells. Absence of staining for keratin in the sarcomatoid tumour cells does not always exclude SCSC, because some SCSCs show immunoreactivity of keratin in their sarcomatoid components only with some anti-keratin antibodies. Different kinds of anti-keratin antibodies should be applied in the differential diagnosis of SCSC.

Aged↗

Clear cell tumors of minor salivary gland origin. An immunohistochemical and ultrastructural analysis.

Three cases of monophasic glycogen-rich clear cell tumors of palatal gland origin were examined immunohistochemically and ultrastructurally in attempts to characterize their cellular composition. Despite their histologic resemblances, the clear cells from each case showed different immunohistochemical features. In case 1 the extensive positivity for vimentin and S-100 protein, in addition to the focal expression of actin and glial fibrillary acidic protein, strongly suggested that the clear cells were myoepithelial in nature. In contrast, the clear cells from case 2 exhibited both keratin and epithelial membrane antigen positivity, as well as ultrastructural features that suggested that they were glandular epithelial in nature. In case 3 no special markers except for keratin could be detected, indicating the less differentiated nature of the clear cells. These results show the heterogeneity of the clear cell tumor group of minor salivary glands.

Actins↗

Aneurysm of the extracranial internal carotid artery caused by fibromuscular dysplasia.

A case of aneurysm of the extracranial internal carotid artery (ICA) caused by fibromuscular dysplasia (FMD) is reported. The patient also had an aneurysm of the contralateral intracranial ICA, but the renal arteries were normal. A review of the literature shows extracranial ICA aneurysms to be uncommon, with only 3% caused by FMD. The surgical management of such difficult lesions at the base of the skull is discussed.

Carotid Artery Diseases↗

Cephalosporin antibiotics. I. Synthesis and structure-activity relationships of 3-thiazoliomethyl derivatives.

The synthesis and the structure-activity relationships of 3-thiazoliomethyl cephalosporins are described. In a series of these parenteral compounds, 2-(2-aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido group was found to be a favorable substituent for the C-7 position of the cephem nucleus. They showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species.

Cephalosporins↗