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Biomedical subjects

A Konno

Publications and source records attributed to A Konno.

At least 19 recordsLinked to original sources
PubMed2001

Characterization of novel natural killer (NK)-cell and gammadelta T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus.

Studies on nasal T/natural killer (NK)-cell lymphoma have been hampered by its tendency to cause necrosis. Thus, the establishment of cell lines of this neoplasm would seem to be valuable. This study attempted to establish cell lines from primary lesions of this tumor, and successfully obtained 2 novel Epstein-Barr virus (EBV)-positive cell lines, SNK-6 and SNT-8, by means of high-dose recombinant interleukin 2. Flow cytometry showed that SNK-6 had an NK-cell phenotype, CD3- CD4- CD8- CD19- CD56+ T-cell receptor (TCR) alpha/beta- TCR gamma/delta-, whereas SNT-8 was CD3+ CD4- CD8- CD19- CD56+ TCR alpha/beta- TCR gamma/delta+. These were consistent with immunophenotypes of their original tumors, and the cell lines had monoclonal EBV clones identical to ones in their original tumors. Thus, the cell lines developed from cells forming the primary lesions. Genotypic analysis showed that SNK-6 had unrearranged TCR and immunoglobulin heavy-chain genes, supporting the conclusion that SNK-6 was of NK-cell lineage. On the other hand, SNT-8 had rearranged TCR beta-, gamma-, and delta-chain genes, and together with its phenotype, SNT-8 proved to be a gammadelta T-cell line. This is the first report of the establishment of cell lines from primary lesions of nasal T/NK cell lymphomas, and the results demonstrated that there are at least 2 lineages, NK- and gammadelta T-cell, in this neoplasm. Moreover, it has been suggested that nasal T/NK cell lymphomas of these lineages may belong to the same clinicopathologic entity because both types of cases shared common clinical and histopathologic features.

Blotting, Southern↗
PubMed2001

Nodularin-Har: a new nodularin from Nodularia.

A cyanobacterial hepatotoxin, nodularin-Har, having a homoarginine instead of an arginine in nodularin, was isolated from Nodularia PCC7804. The structure was elucidated as 1 on the basis of 2D NMR and FABMS. The LD(50) (mouse ip) value of 1 was 70 microg/kg.

Animals↗
PubMed2001

Sialolipoma: a report of seven cases of a new variant of salivary gland lipoma.

AIMS: We propose the designation 'sialolipoma' to establish and characterize a new category of benign lipomatous tumour occurring in salivary glands. Until now, these tumours have not been regarded as a distinct entity in the salivary glands. METHODS AND RESULTS: We evaluated the clinicopathological and immunohistochemical features of seven sialolipomas among 2051 surgically resected primary salivary gland tumours deposited in our files. The seven patients with sialolipoma were five men and two women, aged 20-75 years (mean: 54.4 years). Five tumours had arisen in the parotid gland, one in the soft palate, and one in the hard palate. The tumours ranged from 10 to 60 mm (mean: 38 mm) in maximum diameter. Histologically, the tumours were characterized by a well circumscribed mass composed of glandular tissue and mature adipose elements. The adipose elements in the tumours arising in the parotid gland were more abundant than those arising in the minor salivary gland. The glandular components consisted of ductal, acinar, basal and myoepithelial cells, and closely resembled the cellular and structural compositions of normal salivary gland tissues. These findings were confirmed by immunohistochemical and ultrastructural studies. These components had no atypia, except for the presence of some minor variations, e.g. ductal ectasia with fibrosis and focal oncocytic metaplasia. In all cases, cell proliferative activity, as assessed by Ki67 (MIB1) immunostaining, was low. From these findings, it is likely that our cases were lipomas with secondary entrapment of the salivary gland elements. No recurrence was seen in all cases after superficial parotidectomy, or after surgical excision in the patients with palatal tumours. CONCLUSIONS: We regard sialolipoma as a distinct variant of salivary gland lipoma that can occur in both the major and minor salivary glands. Superficial parotidectomy, or surgical resection in the case of palatal tumours, is an appropriate treatment for this benign tumour.

Adult↗
PubMed2001

Enhancement of submicroscopic damage of the nasal epithelium by topical allergen challenge in patients with perennial nasal allergy.

The purposes of this study were to clarify whether damage of the nasal epithelium exists in patients with nasal allergy, and how the morphology of the epithelium changes after topical allergen challenge. Electron microscopy revealed 2 characteristic features in the nasal epithelium of patients with perennial nasal allergy--an increase in the number of epithelial cells with cytoplasmic vacuoles, and markedly widened intercellular spaces--although these changes were unclear under light microscopy. The density of vacuolated cells significantly increased 24 hours after allergen challenge. Further, the number of eosinophils that were associated with vacuolated cells was significantly higher in patients with nasal allergy than in controls. These morphological changes, thus, were considered to be types of damage to the nasal epithelium associated with nasal allergy. Such changes may be among the causes of nasal hyperreactivity, which is an important feature of nasal allergy.

Administration, Topical↗
PubMed2001

Analysis of the p53 gene in parotid gland cancers: a relatively high frequency of mutations in low-grade mucoepidermoid carcinomas.

Mutations and overexpression of the p53 gene and protein were analyzed in 40 cases with various types of parotid gland cancers. Mutations were found in 12 cases (30%), and low-grade mucoepidermoid carcinomas (43%) and highly malignant carcinomas including adenocarcinoma, salivary duct carcinoma, and undifferentiated carcinoma (56%) showed a relatively high frequency of mutations. Overexpression of the protein was observed in 11 cases (28%) and 4 of the 11 cases also had p53 mutations. These results suggest that mutations of the p53 gene have significance in certain types of parotid cancers irrespective of the aggressiveness of a tumor type.

Carcinoma, Mucoepidermoid↗
PubMed2000

Evaluation of the validity of the 1997 International Union Against Cancer TNM classification of major salivary gland carcinoma.

BACKGROUND: The TNM classification (International Union Against Cancer) of salivary gland carcinoma was revised in 1997. In this study, the authors have evaluated the validity of this new TNM classification and clinical staging in 1683 patients with parotid gland carcinoma. METHODS: Reclassification was conducted according to the new classification based on the clinical data of 1683 patients registered to the salivary gland division of the Japanese Joint Committee on TNM classification. The 5- and 10-year survival rates according to TNM classification were calculated for 1074 patients whose prognosis could be followed up. Finally, the distribution of the total patient population was analyzed using the new staging and the survival curves for each disease stage. RESULTS: The variance of the patients for T1 to T4 was appropriate using the new T classification. The 5- and 10-year survival rates corresponded well to the degree of progression of TNM. However, there were only nine patients with Stage III, and marked nonuniformity in the staging was observed. The separation of the survival curves for each stage was not clear, and no significant differences between the survival curves of Stages II and III and Stages III and IV were observed. When the authors classified T1N1M0, T2N1M0, T3N1N0, and T4N0M0, which have 5- and 10-year survival rates similar to Stage III, distribution of patients and separation of the survival curves in each stage improved markedly. CONCLUSIONS: The results of the current study confirm that the new TNM classification system is valid. However, a significant problem was observed with respect to the new clinical staging. The authors propose that T1N1M0, T2N1M0, T3N1M0, and T4N0M0 be classified as Stage III.

Disease-Free Survival↗
PubMed2000

Isolation and characterization of murine orthologue of PTP-BK.

We isolated and characterized a murine orthologue of PTP-BK, a receptor-type protein tyrosine phosphatase expressed in brain and kidney. The deduced amino acid sequences showed 89, 95, and 92% identities with human, rabbit, and chicken homologues of PTP-BK. Mouse PTP-BK encodes a polypeptide of 1,226 amino acids with calculated molecular weight of 138,598 Da. The mature form of PTP-BK constitutes of 3 domain structures including extracellular, transmembrane, and a single intracellular PTPase domain. Western blot analysis indicated that anti-PTP-BK antibody specifically immunoreacted to 2 distinct molecules of 200 kDa and 220 kDa in COS cells, possibly due to differential glycosylation. The recombinant PTP-BK showed the phosphatase activity specific for the phosphotyrosine, but not for the phosphoserine residue of phosphopeptides in vitro. Radiation hybrid panel assigned mouse PTP-BK gene to 5.02cR distal to from the marker D6Mit339 on chromosome 6. Mouse PTP-BK was classified in PTPRO family in novel nomenclature. We discuss here the diversity and physiological functions of PTPRO family of PTP.

Amino Acid Sequence↗
PubMed2000

Sound-induced laryngeal and respiratory reflexes originate from vestibular afferents.

To determine whether the auditory or vestibular system causes the sound-induced laryngeal reflex, which has been considered to participate in the auditory feedback control of vocalization, click-induced laryngeal responses were compared before and after sectioning of the cochlear and/or vestibular nerves in cats. The sound-induced reflex modulation of respiratory muscle activity was also investigated, because respiratory movement is important for vocal control. Sectioning of the cochlear nerves had little influence on these responses. In contrast, sectioning of the vestibular nerves abolished these responses. It was concluded that the sound-induced laryngeal and respiratory reflexes are attributed to the vestibular system.

Acoustic Stimulation↗
PubMed2000

Primary large-cell neuroendocrine carcinoma of the parotid gland: immunohistochemical and molecular analysis of two cases.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72- and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21Waf1 and p27Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation. Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.

Aged↗
PubMed2000

Interleukin-13 and tumour necrosis factor-alpha synergistically induce eotaxin production in human nasal fibroblasts.

BACKGROUND: There is increasing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. However, the mechanism involved in the production of eotaxin has yet to be clarified. Most recently, it has been shown that interleukin (IL) -4 induces eotaxin in dermal fibroblasts. A novel cytokine termed IL-13, which binds to the alpha-chain of the IL-4 receptor, shares many biological activities with IL-4. It is known that fibroblasts express the IL-4 receptor and produce collagen type I upon stimulation with IL-4. OBJECTIVE: We investigated whether IL-13, as well as IL-4, are able to induce eotaxin production in human nasal mucosal fibroblasts (HNMFs). Furthermore, we investigated the effect of costimulation of IL-13 and TNFalpha on eotaxin production. METHODS: HNMFs, isolated from inferior nasal mucosa samples, were stimulated by various kind of cytokines for 1-36 h at 37 degrees C in 5% CO2. The change in the expression of eotaxin mRNA was then evaluated by reverse transcriptase-polymerase chain reaction and the Southern blot analysis. The amount of eotaxin in the culture media was measured by ELISA. RESULTS: IL-13 as well as IL-4 dose-dependently induced eotaxin expression in HNMFs. Furthermore, IL-13 and TNFalpha synergistically induced eotaxin expression in HNMFs, while they hardly induced eotaxin expression in endothelial cells, epithelial cells or eosinophils. The synergy was observed when pre-incubation of HNMFs with IL-13 was followed by a stimulation with TNFalpha, or HNMFs were simultaneously stimulated with IL-13 and TNFalpha. CONCLUSION: These results strongly indicate that IL-13, as well as IL-4, may be important in eotaxin-mediated eosinophilic inflammation in nasal mucosa. In addition, in nasal mucosa, fibroblasts are the major cell source for eotaxin.

Adult↗
PubMed2000

Transepithelial migration of activated eosinophils induces a decrease of E-cadherin expression in cultured human nasal epithelial cells.

BACKGROUND: The damage of respiratory epithelium in allergic diseases has a close correlation with the extent of eosinophil infiltration. It seems to be a good possibility that eosinophil infiltration could induce the changes in the expression of the epithelial cell adhesion molecules, which play a key role in the maintenance of structural and functional rigidity of epithelium. OBJECTIVE: We observed the expression of E-cadherin in cultured human nasal epithelial cells (HNECs) to study whether could it be affected by transepithelial migration of inflammatory cells, especially eosinophils. METHODS: In vitro study of the transmigration assay was designed using various types of inflammatory cells and HNEC monolayers. Various assays of each experimental group were done under the stimulation of interleukin-5 (IL-5) and/or platelet activating factor (PAF). Subsequently immunohistochemistry for E-cadherin was performed in the HNECs. The intensity of immunofluorescence of E-cadherin was quantified using confocal laser scanning microscopy (CLSM) system and compared before and after the transmigration. RESULTS: The mean intensity of immunofluorescence for E-cadherin decreased significantly after the transmigration of any types of inflammatory cells. Above all, the migration of eosinophils treated with IL-5 and PAF had an eminent effect on the decrease, whereas the degranulation extracts derived from eosinophils activated by IL-5 and secretory IgA (sIgA) did not affect the intensity. CONCLUSION: This work suggests that transepithelial migration of inflammatory cells can directly induce the decrease in epithelial E-cadherin expression. Furthermore, the most prominent change was induced by transmigration of activated eosinophils, which might be caused by some mechanisms independent of the eosinophil contents. The decrease in E-cadherin expression may trigger the damage of epithelial barrier, which contributes to the pathogenesis of allergic diseases.

Adolescent↗
PubMed2000

Role of vascular reflex in nasal mucosal swelling in nasal allergy.

OBJECTIVE: In patients with nasal allergy, antigen challenge on the unilateral nasal mucosa results in nasal secretion not only in the ipsilateral but also in the contralateral nasal cavities that can be inhibited almost completely by premedication with atropine sulfate. The present study was performed to elucidate if centrally mediated vascular reflex induced by antigen challenge plays a role in nasal mucosal swelling in subjects with nasal allergy. METHODS: Variations of mucosal swelling and mucosal blood flow in the ipsilateral and the contralateral nasal cavities after unilateral antigen challenge were evaluated by acoustic rhinometry and laser Doppler flowmetry in 20 patients with perennial nasal allergy. RESULTS: Unilateral antigen challenge caused ipsilateral and contralateral nasal mucosal swelling in 17 and 13 patients, respectively. Incidence of contralateral nasal mucosal swelling after unilateral antigen challenge was significantly higher compared with that after control disc challenge (P < .001). In 10 patients in whom unilateral antigen challenge caused bilateral nasal mucosal swelling, significant swelling of the nasal mucosa lasted for more than 30 minutes in the ipsilateral nasal cavity after antigen challenge compared with only 15 minutes in the contralateral nasal cavity. Peak values of contralateral mucosal swelling were 45.3% of those of ipsilateral nasal mucosa. CONCLUSIONS: Centrally mediated vascular reflex is partially involved in the onset of nasal mucosal swelling observed after antigen challenge in subjects with nasal allergy. However, nasal mucosal swelling that persists and proceeds even 20 minutes after antigen challenge is caused by the direct effects of chemical mediators on the nasal vasculature.

Adolescent↗
PubMed2000

Time course of changes in absorption of macromolecule through the nasal mucosa after antigen challenge in guinea pig model of allergic rhinitis.

The time course of changes in absorption of horseradish peroxidase (HRP) through the nasal mucosa after antigen challenge was evaluated in a guinea pig model of allergic rhinitis immunized with ovalbumin. Before and at 5 minutes, 4 hours, and 24 hours after nasal antigen challenge, both nasal cavities were filled with 5% HRP solution for 30 minutes, and blood was obtained to measure serum HRP levels by enzyme-linked immunosorbent assay. In immunized animals, the serum HRP levels were 2.3 times higher than those of normal controls (p<.05) before antigen challenge, which was performed 7 days after a series of nasal antigenic sensitizations. At 5 to 35 minutes after antigen challenge, the HRP levels decreased to one sixth of the prechallenge levels (p<.05), and they did not show a difference from the control levels. However, they increased markedly at 4 and 24 hours after antigen challenge (p<.01). The present study suggests that the absorption of macromolecules through the allergic nasal mucosa is enhanced markedly, depending upon the time course after antigen challenge, although it shows no apparent difference from normal controls during the dominant exudative process.

Absorption↗
PubMed2000

Immunohistochemistry for parathyroid hormone-related protein (PTHrP) in benign and malignant mammary mixed tumors of dogs with and without hypercalcemia.

We evaluated the expression of parathyroid hormone-related protein (PTHrP) by immunohistochemistry in eight benign and malignant mammary mixed tumors of dogs with (n = 4) and without (n = 4) hypercalcemia. Positive immunoreactive staining for PTHrP was observed in all four tumors from hypercalcemic dogs. The mammary tumors from 2 of the 4 normocalcemic dogs stained positively for PTHrP, but the numbers of immunoreactive cells and intensity of the immunoreaction were less than in the hypercalcemic dogs. In the other 2 tumors without hypercalcemia, the tissue samples were negative for PTHrP.

Animals↗
PubMed2000

[Long-term result after UPPP for OSAS by evaluation of nocturnal oxygenation].

The nocturnal oxygenation of 45 patients with OSAS who had UPPP at our hospital were evaluated by pulse oximetry before and after surgery and at the time more than one year after UPPP. "Successful case" is defined as the case that showed more than 50% reduced oxygen desaturation index(ODI) after UPPP. Twenty seven cases including 15 severe cases(ODI > or = 40) have showed continuously successful ODI for more than one year. We could not get good result in 8 cases, which kept high ODI. Four of them are now using dental appliance. We have recognized the recurrence of sleep apnea in 10 cases that once got successful results just after UPPP. Our report strongly suggests the importance of long-term follow-up after surgery.

Circadian Rhythm↗
PubMed1999

Ablation of a specific cell population by the replacement of a uniquely expressed gene with a toxin gene.

The transgenic expression of a toxin gene or a thymidine kinase gene under the control of cell type-specific promoter/enhancer has been shown to be useful for removing a specific cell population in mice. However, this approach requires extensive analysis of the control elements for gene expression in the preparation of the transgenic constructs, and furthermore, the toxin gene might be expressed ectopically because of random integration, resulting in aberrant depletion of unrelated cells. To avoid such difficulties with the transgenic approach, we established a method for the specific depletion of a cell population by replacing a uniquely expressed gene in the population with the diphtheria toxin gene by using homologous recombination. The NKR-P1 gene, a specific cell surface marker of natural killer (NK) cells, was selected as the target gene for depleting NK cells. In chimeric mice reconstituted with embryonic stem cells in which the NKR-P1 gene was replaced by the toxin gene, NKR-P1(+) cells were almost completely depleted, and NK cell function was abrogated in the embryonic stem cell-derived lymphoid cells. Other cell lineages developed normally. These results show that all NK cells express NKR-P1, that NKR-P1(+) cells do not influence the development of T and B cells, and further, that this technology of cell targeting is a fast and powerful method of generating mice lacking any chosen cell population.

Animals↗