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Biomedical subjects

M Tashiro

Publications and source records attributed to M Tashiro.

At least 145 records · Page 8Linked to original sources
PubMed1992

Stimulation of growth by both androgen and estrogen of the EMP-K1 transplantable tumor with androgen and estrogen receptors from human extramammary Paget's disease in nude mice.

BACKGROUND: Experimental approaches using transplantable human tumors in nude mice have greatly improved studies on their pathogenesis and treatment. PURPOSE: We studied the establishment of a transplantable tumor, EMP-K1, derived from extramammary Paget's disease and the morphology and unique hormone dependence of this tumor. METHODS: Tissue fragments from a metastatic skin tumor of an 80-year-old man with primary genital extramammary Paget's disease were implanted into male nude BALB/c mice. Tissue fragments of the established tumor were implanted into 50 castrated male 8-week-old nude mice, which were given injections of 100 micrograms testosterone propionate (TP), 100 micrograms 5 alpha-dihydrotestosterone (DHT), 10 micrograms diethylstilbestrol (DES), or 1, 10, or 100 micrograms 17 beta-estradiol (E2). All injections were administered intramuscularly once daily, starting from the day of transplantation. The established tumors were examined immunohistochemically and biochemically. RESULTS: A transplantable tumor (EMP-K1) was established in the nude mouse. EMP-K1 tumor cells expressed antigens such as carcinoembryonic antigen and epithelial membrane antigen, cytokeratin, and c-erbB-2 protein and contained androgen, estrogen, and progesterone receptors. The growth of the EMP-K1 tumor was stimulated by TP, DHT, DES, and E2. CONCLUSIONS: These results suggest that both androgen and estrogen may stimulate the growth of the same tumor by both androgen receptor and estrogen receptor pathways. IMPLICATIONS: The EMP-K1 tumor is a useful tool for studies on the biology of extramammary Paget's disease, and further studies using these tumors will provide useful information concerning proper hormone therapy.

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PubMed1992

Significance of basolateral domain of polarized MDCK cells for Sendai virus-induced cell fusion.

Fusion (fusion from within) of polarized MDCK monolayer cells grown on porous membranes was examined after infection with Sendai viruses. Wild-type virus, that buds at the apical membrane domain, did not induce cell fusion even when the F glycoprotein expressed at the apical domain was activated with trypsin. On the other hand, a protease activation mutant, F1-R, with F protein in the activated form and that buds bipolarly at the apical and basolateral domains, caused syncytia formation in the absence of exogenous protease. Anti-Sendai virus antibodies added to the basolateral side, but not at the apical side, inhibited cell fusion induced by F1-R. In addition, T-9, a mutant with bipolar budding phenotype of F1-R but with an uncleavable F protein phenotype like wild-type virus, induced cell fusion exclusively when trypsin was added to the basolateral medium. By electron microscopy, cell-to-cell fusion was shown to occur at the lateral domain of the plasma membrane. These results indicate that in addition to proteolytic activation of the F protein, basolateral expression of Sendai virus envelope glycoproteins is required to induce cell fusion.

Animals↗
PubMed1992

Budding site of Sendai virus in polarized epithelial cells is one of the determinants for tropism and pathogenicity in mice.

Wild-type Sendai virus fusion (F) glycoprotein requires trypsin or a trypsin-like protease for cleavage-activation in vitro and in vivo, respectively. The virus is pneumotropic in mice and buds at the apical domain of bronchial epithelial cells. On the other hand, the F protein of the protease-activation host range mutant, F1-R, is cleaved by ubiquitous proteases present in different cell lines and in various organs of mice. F1-R causes a systemic infection in mice and the mutant buds bipolarly at the apical and basolateral domains of infected epithelial cells. The enhanced cleavability of the F protein of F1-R has been shown to be a primary determinant for pantropism. Additionally, it has been postulated that bipolar budding of F1-R is required for the systemic spread of the virus and it has been attributed to mutations in the matrix (M) protein of F1-R (Tashiro et al., Virology 184, 227-234, 1991). In this study protease-activation mutants (KD series) were isolated from wild-type virus. They were revealed to bud at the apical domain, and the F protein was cleaved by ubiquitous proteases in mouse organs. The KD mutants were exclusively pneumotropic in mice following intranasal infection, whereas they caused a generalized infection when inoculated directly into the circulatory system. Comparative nucleotide sequence analysis of the F gene of the KD mutants revealed that the deduced amino acid substitutions responsible for enhanced cleavability of the F protein occurred removed from the cleavage site. Mutations were not at all found in the M gene of the KD mutants analyzed, in support of the role of the M protein of F1-R and of a revertant T-9 derived from the latter in bipolar budding. These results suggest that bipolar budding is necessary for the systemic spread of F1-R from the lungs and that apical budding by wild-type virus and the KD mutants leads to respiratory infections. Differential budding at the primary target of infection, in addition to the cleavage-activation of the F protein in mouse organs, is therefore also a determinant for tropism and pathogenicity of Sendai virus in mice.

Amino Acid Sequence↗
PubMed1992

Differences in HTLV-I integration patterns between skin lesions and peripheral blood lymphocytes of HTLV-I seropositive patients with cutaneous lymphoproliferative disorders.

We examined HTLV-I integration patterns in nine cases of HTLV-I-seropositive patients with cutaneous lymphoproliferative disorders. The Southern blot on EcoRI digests of DNA revealed a discrete band of HTLV-I provirus (monoclonal integration) in either skin lesions or peripheral blood lymphocytes (PBL). Four cases showed the monoclonal integration of HTLV-I provirus only in skin lesions: one case showed only in PBL and two cases showed in both skin and PBL. The Southern blot on PstI digests of DNA revealed a 2.4 Kb band of the internal construct of HTLV-I provirus (polyclonal integration) in the PBL of EcoRI-negative samples. The difference in HTLV-I integration patterns between skin lesions and PBL in these cases suggests that the monoclonal outgrowth of HTLV-I-infected cells in the skin is causatively associated with the pathogenesis of cutaneous ATL.

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PubMed1992

Interactions between bacteria and influenza A virus in the development of influenza pneumonia.

Different proteases from various microorganisms present in the respiratory tract were capable of enhancing influenza virus infectivity and pathogenicity in mice by proteolytic activation of hemagglutinin (HA). Aerococcus viridans, isolated from a patient with pneumonia, secreted a protease that could activate HA directly, similarly to some Staphylococcus aureus strains. The protease of Pseudomonas aeruginosa could not activate HA directly, but combined application of P. aeruginosa protease and virus into mice enhanced virus titers and pathogenicity. Generation of trypsin-like activity in bronchoalveolar lavage fluids resulting from this combination treatment may be responsible for HA activation. A similar indirect effect on HA activation was induced by streptokinase and staphylokinase, which are known to generate plasmin by plasminogen activation. It was concluded that plasminogen-activating streptococci and staphylococci facilitate viral replication and pathogenicity of plasmin-sensitive influenza virus strains by amplification of the plasminogen/plasmin system.

Animals↗
PubMed1992

Changes in specific cleavability of the Sendai virus fusion protein: implications for pathogenicity in mice.

Sendai virus mutants, KDe-21 and KDe-62, which had undergone multiple cycles of replication in Madin Darby canine kidney (MDCK) cells in the absence of exogenous proteases were isolated. The fusion (F) protein of the mutants regained proteolytic cleavability in MDCK cells and chick embryos, but the F protein remained non-cleavable in other cell lines. Unlike the F protein of wild-type (wt) virus, the mutant F was resistant to trypsin but was sensitive to elastase and, to a lesser extent, to chymotrypsin. Sequence analyses of the F gene and the F protein revealed an amino acid substitution at the cleavage site, Arg(116) to Ile, which conferred trypsin resistance and enhanced cleavability at Ile(116) by elastase and host proteases present in MDCK cells and in chicken embryos. In contrast to the pneumopathogenicity in mice of wt Sendai virus, the KDe mutants were non-pathogenic; cleavage activation of the F protein did not occur in the lungs and thereby infection was terminated after an initial cycle of replication.

Amino Acid Sequence↗
PubMed1992

Expression of human T-cell lymphotropic virus type-1 gene products in the short-term cultured skin tissues of an adult T-cell leukemia/lymphoma patient with cutaneous manifestations.

Adult T-cell leukemia/lymphoma (ATLL) is recognized as a disease etiologically associated with human T lymphotropic virus type-1 (HTLV-1) infection, but, neither viral replication nor specific virus antigen expression have been detected on ATLL cells distributed in organs, including skin. To examine the latent expression of HTLV-1 in the cutaneous lesions of ATLL patients, we cultured the lesional skin tissues in vitro and applied immunofluorescence staining with mouse monoclonal antibodies Lt-4, GIN-14, and F10, which react with p40tax, p19 and gp21, respectively. We recognized HTLV-1 specific antigens on clustered ATLL cells only in the deeper dermis of the skin after 24 hrs cultivation of the lesional skin tissue from an ATLL patient in RPMI-1640 medium supplemented with 20% fetal calf serum. In the electron microscope, we observed HTLV-1 like particles, 80-140 nm in diameter with envelope and core structures, in the same tissue specimen. These findings suggest that HTLV-1 gene products may be expressed in the skin lesions of ATLL patients and involved in the pathogenesis of skin eruptions in cutaneous type ATLLs. To our knowledge, this is the first report that envisages the potency of intracutaneous HTLV-1 expression in vivo.

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PubMed1992

A case of intravascular malignant lymphomatosis (angiotropic large-cell lymphoma) presenting memory T cell phenotype and its expression of adhesion molecules.

A case of intravascular malignant lymphomatosis (angiotropic large cell lymphoma), T cell type was reported. The patient, a 59-year-old woman, had reddish or violaceous indurated macules scattered over the entire body surface. Neither lymphadenopathy nor hepatosplenomegaly was recognized. A chest Roentgenogram, whole body CT scan, and 67Ga-citrate scintigraphy yielded normal findings. Serum anti-HTLV-1 antibody was negative. Histopathologically, lesions showed intravascular large mononuclear cell proliferation associated with occasional fibrin thrombi formation in the dermis to subcutis. Immunohistochemically, the large mononuclear cell immuno-phenotype had a memory T cell character. Also, both lymphocyte function-associated antigen-1s, CD11a and CD18, and intercellular adhesion molecule-1 were demonstrated on the tumor cells and vascular walls in the lesions. To our knowledge, the present case is the fourth case of intravascular malignant lymphomatosis in the T cell lineage.

Cell Adhesion Molecules↗
PubMed1992

Significance of the serum CA125 level in recurrent ovarian cancer.

Thirty-four recurrent cases of 89 patients with ovarian cancer treated in our department between 1985 and 1989 were examined for changes in serum CA125 level. 1) Upon confirmation of recurrence, 17 patients were positive for CA125 and 15 were negative. 2) According to the histopathological type, the rate of CA125 positivity in patients with recurrence was high for serous adenocarcinoma, suggesting that determination of CA125 is useful for detection of recurrence. In contrast, all patients with mucinous adenocarcinoma or endometrioid adenocarcinoma were negative for CA125. 3) The CA125 positivity rate upon confirmation of recurrence was 9% in patients whose CA125 was less than 1,000 U/ml on initial examination, suggesting that close management of such patients is necessary. 4) Elevation of CA125 by 3 steps or more within the normal range (less than 35 U/ml) was useful for predicting recurrence. 5) The cut-off level of CA125 during follow-up should be set at 16 U/ml. 6) It was difficult to evaluate remission with only the serum CA125 level. It is impossible to avoid second look operation at present. These results indicate that pretreatment values and changes of the parameter within the normal range (less than 35 U/ml) have to be considered when using CA125 as a marker of tumor recurrence.

Adenocarcinoma↗
PubMed1992

Tryptase Clara, an activating protease for Sendai virus in rat lungs, is involved in pneumopathogenicity.

Tryptase Clara is an arginine-specific serine protease localized exclusively in and secreted from Clara cells of the bronchial epithelium of rats (H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma, J. Biol. Chem. 267:13573-13579, 1992). The purified protease was shown in vitro to behave similarly to trypsin, cleaving the precursor glycoprotein F of Sendai virus at residue Arg-116 and activating viral infectivity in a dose-dependent manner. Anti-tryptase Clara antibody inhibited viral activation by the protease in vitro in lung block cultures and in vivo in infected rats. When the enzyme-specific antibody was administered intranasally to rats that were also infected intranasally with Sendai virus, activation of progeny virus in the lungs was significantly inhibited. Thus, multiple cycles of viral replication were suppressed, resulting in a reduction in lung lesions and in the mortality rate. These findings indicate that tryptase Clara is an activating protease for Sendai virus in rat lungs and is therefore involved in pulmonary pathogenicity of the virus in rats.

Animals↗
PubMed1992

Increased mitochondrial DNA deletions in the skeletal muscle of myotonic dystrophy.

Mitochondrial abnormality in the skeletal muscles of 13 patients with myotonic dystrophy was analyzed by both histochemical and molecular biologic methods. Nine of 13 patients had ragged-red fibers (50 +/- 116 per 10,000 muscle fibers, mean +/- SD), and 10 patients had cytochrome c oxidase-negative fibers (41 +/- 90 per 10,000 muscle fibers). Southern blot analysis detected no mitochondrial DNA deletions, while PCR revealed multiple mitochondrial DNA deletions in all the specimens. Direct sequencing of one of the deleted mitochondrial DNAs disclosed that the junctional sequence of a 3,460-bp deletion involved a 6-bp directly repeated sequence (5'-TAGAAG-3') flanked by C-rich regions located on the CO3 gene and the ND5 gene. Quantitative analysis of PCR amplified deleted mitochondrial DNAs revealed that the amount of deleted mitochondrial DNAs had positive correlation both with the frequencies of ragged-red fibers and cytochrome c oxidase-negative fibers. Although deleted mitochondrial DNAs were observed even in controls above age 30, the mean amount of deleted mitochondrial DNAs in patients with myotonic dystrophy was significantly higher than in controls. Moreover, the increase of deleted mitochondrial DNAs with aging was more marked in myotonic dystrophy than in controls. These results suggest that increased mitochondrial DNA deletions and consequent impairment of mitochondrial function contribute to the pathophysiology of myotonic dystrophy.

Adolescent↗
PubMed1992

[Quantitative skeletal muscle pathology of aging regarding ragged-red fibers and cytochrome c oxidase-negative fibers].

A statistical analysis of mitochondrial abnormality of aging in human skeletal muscle fibers was performed. Sixty one muscle samples were obtained from patients with acute medical illness autopsied strictly within 2 hours after death, or with orthopedic or surgical diseases biopsied with informed consents. The patients aged from 16 to 89, averaging 58 +/- 21 years in males and 21 to 92, averaging 55 +/- 20 years in females. Sections were stained by modified Gomori's trichrome, succinate dehydrogenase and cytochrome c oxidase-negative [CCO(-)] fibers approximately in 10,000 fibers in each muscle were evaluated. Both RRF and CCO (-) fibers were not observed below the fourth decade, but sequentially increased with age, especially after the seventh decade. The incidence of CCO (-) fibers was higher than that of RRF. RRF did not necessarily correspond to CCO (-) fibers. The present quantitative pathological result is a useful tool to evaluate the mitochondrial function in fresh human skeletal muscles by the age.

Adolescent↗
PubMed1992

[A case of insulin receptor abnormality (type A)].

A sixteen year old woman came to the hospital for glucosuria and amenorrhea. Physical examination demonstrated that she had hirsutism, deepening of voice, and pigmented skin in her axillary lesion which was histologically diagnosed as acanthosis nigricans. Ultrasonography showed polycystic ovaries. A diabetic pattern of 75 g oral glucose tolerance test, very high levels of serum insulin (fasting: 320, peak: 1,220 microU/ml), and hyperandrogenism characterized by increases of urine 17-KS, serum testosterone and DHEA-S were found. Both serum insulin and insulin-receptor antibodies were found to be negative. Insulin binding to both erythrocytes and cultured skin fibroblasts were significantly decreased (about 30% of normal controls). Scatchard plot analysis demonstrated decreased number of insulin receptors to about 30% of the normal controls. We therefore diagnosed that she had insulin receptor abnormality, Type A in Kahn's classification.

Acanthosis Nigricans↗
PubMed1992

[A new method for endotracheal intubation with the Bullard laryngoscope].

The Bullard laryngoscope is an anatomically shaped rigid fiber optic instrument designed for indirect laryngoscopy and intubation. It requires no neck extension nor flexion to perform laryngeal intubation. This characteristic is especially useful in the case of difficult airway. The Bullard laryngoscope, however, with which it is easy to visualize the cords, has not been popular yet, because using the intubating forceps mechanism requires a certain amount of skill. The intubation method developed by us with Bullard laryngoscope has been tried on 26 patients with difficult airway and ten patients with normal airway. An endotracheal tube is inserted through nostril, and intubation is performed viewing the tube and larynx during all the processes of intubation. Three kinds of endotracheal tubes, i.e. Magill type plain tubes, styletted tubes, and directional tip tubes, are compared. The method using a directional tip tube (Endotrol) is concluded as the best among them. The Endotrol tube itself has such a suitable shape for nasal intubation that it can be introduced to the larynx with little directional change. Therefore, our method is mastered with a shorter training period than the intubation method with fiber-optic laryngoscopes. In conclusion, our intubation method with the Bullard laryngoscopes using the directional tip tubes (Endotrol) is useful for patients with difficult airways, and is also nontraumatic and easy to perform.

Humans↗
PubMed1991

Direct DNA sequencing from colony: analysis of multiple deletions of mitochondrial genome.

We have developed a rapid and efficient nucleotide sequencing technique, named the colony direct sequencing method, which combines both the conventional cloning method for picking up a single gene and the polymerase chain reaction (PCR) method for amplifying the gene directly from a colony. In the present study, the colony direct PCR product was used both for identification of the DNA insert and for nucleotide sequencing by an automated DNA analysis system. A nucleotide sequence of 300 to 400 bp could be determined within 13 h after picking the bacterial colonies on LB medium plates. We applied this method to sequencing of junctional regions of multiple deleted mtDNAs in two siblings with inherited recurrent myoglobinuria. Mitochondrial DNA fragments with deletions were amplified by PCR and then cloned into plasmids. Among 48 white colonies propagated on LB medium plates, nine different clones were identified by PCR directly from colonies. Determination of six different junctional sequences disclosed involvement of directly repeated sequences of 2 to 12 bp in length on each side of the deletions. We believe that the colony direct sequencing method will be a powerful tool in molecular genetics for identification of a single gene among polymorphic DNAs.

Adenosine Triphosphatases↗
PubMed1991

[Tumor embolism of pulmonary arteries and subsequent pulmonary infarction observed in two hepatocellular carcinoma cases].

Tumor emboli of the pulmonary arteries are infrequent and premortem detection of this lesion is rare. We encountered two cases of hepatocellular carcinoma associated with tumor emboli of the pulmonary arteries and subsequent pulmonary infarctions. Plain radiographs and CT demonstrated multiple metastatic pulmonary nodules as well as pleural-based pulmonary consolidations representing pulmonary infarctions. Postcontrast CT also showed filling defects in the main pulmonary arteries. These radiographic and CT features are considered to be characteristic of tumor emboli of pulmonary arteries and subsequent pulmonary infarction. In one patient whose initial symptoms were chest pain and bloody sputum, CT was useful in detecting the primary site of tumor emboli of the pulmonary arteries. It should be kept in mind that neoplasm with a tendency to venous invasion can cause tumor emboli of the pulmonary arteries and subsequent pulmonary infarction.

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