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S Nonaka

Publications and source records attributed to S Nonaka.

At least 37 records · Page 2Linked to original sources

Association of human papillomavirus type 6 with a verruciform xanthoma.

We report a case of verruciform xanthoma (VX) associated with human papillomavirus (HPV) in a 67-year-old male. The patient had a pale-reddish, granular and verrucous tumor on the right side of his scrotum for four years. Histopathologic examination showed typical features of VX. HPV was detected by immunohistochemistry, electron microscopy, and PCR examinations. Ultrastructural examination revealed virus-like particles of 40-50 nm in the nucleus of the upper epidermal keratinocytes. HPV type 6a DNA was detected in lesional tissue by polymerase chain reaction and sequence analysis. To the best of our knowledge, this is the first case report of VX associated with HPV.

Aged↗

Inhibitory effects of Alpinia speciosa K. SCHUM on the porphyrin photooxidative reaction.

It is thought that the beta-carotene defense mechanism against photosensitivity involves the inhibition of singlet oxygen formation, a kind of active oxygen. When we screened chemical substances obtained from plants indigenous to Okinawa, known to have residents with the longest life span in Japan, we found that Alpinia speciosa K. SCHUM (Japanese name: gettou), which is used as a food preservative, has an activity similar to that of beta-carotene. We measured the amount of lipid peroxide (LPO) formed from a hematoporphyrin-containing rat liver microsomal suspension irradiated with visible light. The inhibitory effect of Alpinia speciosa on LPO formation was confirmed when the addition of increasing concentrations of Alpinia speciosa extract led to a decrease in the amount of LPO formed. Moreover, the reaction mechanism that affects the amount of singlet oxygen formed was measured, and the effect of the extract was determined by the ESR trapping technique. It was found that the extract effectively inhibited the formation of singlet oxygen. The extract of Alpinia speciosa contains dihydro-5,6-dehydrokawain. It was confirmed that dihydro-5,6-dehydrokawain, which is a water-soluble compound, has singlet oxygen quenching activity. We synthesized five derivatives of kawain and found that dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl] phosphorothionate has the strongest singlet oxygen quenching activity. The use of the compound from Alpinia speciosa that exhibits singlet oxygen quenching activity as an inhibitory agent of the phototoxic reaction in porphyria is expected.

Animals↗

Inhibitory effect of Rumex Japonicus Houtt on the porphyrin photooxidative reaction.

Rumex Japonicus Houtt (RJH), a plant indigenous to Okinawa, Japan, has been used traditionally by the local people for treatment of acute and chronic cutaneous diseases; however, its pharmacological effect is not clearly understood. To investigate its active function, we examined the antioxidative effect of RJH on the hematoporphyrin-induced photooxidative reaction. We measured intracellular reactive oxygen species (ROS) in cultured transformed human vascular endothelial cells (ECV-304) by flow cytometry, lipid peroxide (LPO) in erythrocyte ghosts by spectrofluorometry, and hemolysis by spectrophotometry. Results showed the generation of intracellular ROS in ECV-304, LPO production in erythrocyte ghosts, and hemolysis after visible light irradiation in the presence of hematoporphyrin. In the RJH root extract treated group, generation of intracellular ROS, LPO production, and hemolysis were inhibited significantly. It has been reported that the RJH root contains emodin and chrysophanic acid. In our study, three fractions were separated from the RJH root extract by thin layer chromatography (TLC). We found that fraction 1 (near the origin) showed a strong inhibitory effect on LPO levels; however, fraction 2 (equal to emodin) and fraction 3 (equal to chrysophanic acid) showed no inhibitory effect on LPO levels. Our experiments verified that RJH has an antioxidative effect against photohemolysis and supports our hypothesis that RJH may have potential as a protective agent against oxidative stress associated with some diseases such as porphyrias.

Absorption↗

Tyrosine kinase inhibitors reduce bcl-2 expression and induce apoptosis in androgen-dependent cells.

The signal transduction pathway showing how androgen withdrawal induces apoptosis in androgen-dependent cells has not been clearly understood. In these studies, we focused on the behavior of tyrosine kinases in androgen-dependent cells and investigated its correlation with apoptosis and bcl-2 expression. We used SC2G, an androgen-dependent mouse mammary carcinoma cell line, which had been cloned from Shionogi Carcinoma 115 (SC115). When SC2G cells were cultured with herbimycin A (HMA), a potent tyrosine kinase inhibitor, the number of viable cells decreased significantly after 24 h. Terminal deoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling and flow cytometric analysis of annexin V staining showed that HMA induced apoptosis of SC2G cells. The level of bcl-2 mRNA in SC2G cells was suppressed by HMA in a dose-dependent manner on RT-PCR. Preincubation with caspase inhibitors protected HMA-induced apoptosis of SC2G cells. When a human bcl-2 gene was transfected in SC2G cells and overexpressed, SC2G cells seemed to acquire tolerance for HMA. These data indicate that HMA-sensitive tyrosine kinase(s) can regulate apoptosis and inhibit bcl-2 expression in SC2G mouse androgen-dependent cells. Tyrosine kinase(s) seemed to be a member of signal transduction between androgen receptor activation and bcl-2 expression.

Animals↗

[Prognostic factors in non-Hodgkin's lymphoma of Waldeyer's ring and the lymph nodes of the neck].

Prognostic factors and treatment outcome of 74 patients with non-Hodgkin's lymphoma of Waldeyer's ring (male 34, female 16, median age 63 years) and cervical lymph nodes (male 17, female 7, median age 62 years) were analyzed retrospectively. The prognostic factors analyzed were: age, B-symptoms, serum LDH levels, and Ann Arbor stage. We also analysed the TNM classification (1987) of Waldeyer's ring lymphoma (previously referred as nasopharyngeal and oropharyngeal cancer) as a new prognostic factor. The 5-year-survival rate of the patients with Waldeyer's ring non-Hodgkin's lymphoma was 67%, compared with 34% for cervical lymph node lymphoma. In univariate analyses, unfavorable outcome was associated with age (age > 60 years), B-symptoms, elevated serum LDH level, and stage. Multivariate analysis showed that age and elevated serum LDH level were significant independent risk factors for death. The 5-year-survival rate according to TNM classification of Waldeyer's ring lymphoma was: T1 (4 cases) 75%, T2 (23 cases) 83%, T3 (10 cases) 56%, T4 (4 cases) 0%; according to N stage, N0 (15 cases) 91%, N1 (7 cases) 73%, N2 (11 cases) 55%, N3 (5 cases), M1 (3 cases) 0%, and according to TNM stage, stage I (one case) stage II (9 cases) 100%, stage III (12 cases) 80%, stage IV (19 cases) 34%. These results suggest that the N classification of Waldeyer's ring non-Hodgkin's lymphoma may be a new prognostic factor.

Age Factors↗

Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis.

KIF3A is a classical member of the kinesin superfamily proteins (KIFs), ubiquitously expressed although predominantly in neural tissues, and which forms a heterotrimeric KIF3 complex with KIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockout mice. kif3A-/- embryos displayed severe developmental abnormalities characterized by neural tube degeneration and mesodermal and caudal dysgenesis and died during the midgestational period at approximately 10.5 dpc (days post coitum), possibly resulting from cardiovascular insufficiency. Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels. These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis.

Animals↗

Developmental changes in histochemical properties of intrinsic laryngeal muscles in rats.

OBJECTIVE: Using neonatal rats, the developmental changes in muscle fiber type of the intrinsic laryngeal muscles were analyzed. The potential influence of two factors were also studied, that were predicted would influence developmental changes in muscle fiber type, denervation and hypothyroidism. METHODS: Using the histochemical technique of myosin ATPase staining, postnatal changes in the ratio of muscle fiber types of each intrinsic laryngeal muscle were determined. In addition, to clarify factors influencing the development of the intrinsic laryngeal muscles, the same technique was employed to study recurrent laryngeal nerve-denervated rats and rats with experimentally-induced hypothyroidism. RESULTS: In normal pups, type 2C fibers had almost disappeared by postnatal day (PND) 14. In denervated pups, differentiation to type 1 and 2A muscle fibers was not observed. In contrast, differentiation to type 2B muscle fibers was impaired in the hypothyroid pups. CONCLUSION: The differentiation of intrinsic laryngeal muscles occur earlier than that of hindlimb muscles. Each intrinsic laryngeal muscle exhibits a particular pattern of developmental changes in normal pups. The developmental changes in the intrinsic laryngeal muscles are affected by recurrent laryngeal nerve innervation and thyroid hormonal control. The findings suggest that both recurrent laryngeal nerve innervation and thyroid hormone play important roles in the differentiation of the intrinsic laryngeal muscles.

Animals↗

Alteration of mRNA levels of delta-aminolevulinic acid synthase, ferrochelatase and heme oxygenase-1 in griseofulvin induced protoporphyria mice.

Human erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism and its experimental murine model can be produced by treatment with griseofulvin (GF). We investigated the alteration of mRNA expression in ferrochelatase (FeC), delta-aminolevulinic acid synthase (ALAS) and heme oxygenase-1 (HO-1) in liver, skin and peripheral blood cells of GF-treated mice. In liver, ALAS mRNA was enhanced dramatically by GF administration, in accord with thesis that the expression of ALAS is regulated by feedback mechanism. The expression of HO-1 mRNA increased most rapidly and drastically in liver, however its mechanism of regulation may be different from that of ALAS mRNA. The level of FeC mRNA in liver was less affected with GF treatment. Our results indicate that the inhibition of FeC by GF administration might occur primarily at post-transcriptional level. Similar effects were observed in the ALAS and HO-1 mRNA expression in peripheral blood cells, 2-fold increase in the ALAS mRNA and increase from undetectable level to detectable level in the HO-1 mRNA. In skin of GF-treated mice, average increases of 1.3-fold in the ALAS mRNA and 1.6-fold in the HO-1 mRNA were statistically insignificant. The FeC mRNA level was not altered in peripheral blood or in skin of GF-treated mice. The present study indicates that the molecular analysis is practicable in skin and peripheral blood. In further study, this model could contribute to investigate the pathogenesis of clinical manifestation including possibly cutaneous changes in EPP.

5-Aminolevulinate Synthetase↗

Abnormal nodal flow precedes situs inversus in iv and inv mice.

We examined the nodal flow of well-characterized mouse mutants, inversus viscerum (iv) and inversion of embryonic turning (inv), and found that their laterality defects are always accompanied by an abnormality in nodal flow. In a randomized laterality mutant, iv, the nodal cilia were immotile and the nodal flow was absent. In a situs inversus mutant, inv, the nodal cilia was motile but could only produce very weak leftward nodal flow. These results consistently support our hypothesis that the nodal flow produces the gradient of putative morphogen and triggers the first L-R determination event.

Animals↗

Detection of human papilloma virus type 56 in extragenital Bowen's disease.

A case of Bowen's disease arising on the medial part of the first metatarsal bone of an 81-year-old Japanese woman is described. Histopathologically, proliferation of atypical cells was found throughout the epidermis. Electronmicroscopy revealed virus particles 40-50 nm in diameter in the nuclei of tumour cells at the granular cells just on or below the horny layer. Positive bands were obtained by polymerase chain reaction using a consensus primer of human papilloma virus L1 portion. Sequencing analysis of the amplified DNA revealed the same base sequences and homology as human papilloma virus 56. To the best of our knowledge, this case is the first report in which human papilloma virus 56 was found in a case of extragenital Bowen's disease. We consider it important to understand that human papilloma virus 56, often found in cervical lesions, can be detected in extragenital Bowen's diseases.

Aged↗

Mast cell "densities" in vascular proliferations: a preliminary study of pyogenic granuloma, portwine stain, cavernous hemangioma, cherry angioma, Kaposi's sarcoma, and malignant hemangioendothelioma.

The "densities" of mast cells (MCs) in six kinds of vascular proliferation, pyogenic granuloma, portwine stain, cavernous hemangioma, cherry angioma, Kaposi's sarcoma, and malignant hemangioendothelioma (MHE), measured per mm2 were studied using respective specimens prepared with tryptase stain and a personal computer. The average densities of MCs in pyogenic granuloma and MHE were 103.5 +/- 25.2/mm2 (n = 10) and 106.3 +/- 40.2/mm2 (n = 10) [mean +/- standard deviation (SD)]; that in normal skin was 6.85 +/- 4.9/mm2 (n = 20) (mean +/- SD). is a significant difference [t-test (p < 0.0001) and Wilcoxon-test (p < 0.01)]. The results in portwine stain (n = 4), cavernous hemangioma (n = 9), cherry angioma (n = 4), and Kaposi's sarcoma (n = 4) were 68.6 +/- 28.9/mm2, 105.7 +/- 56.9/mm2, 85.3 +/- 45.6/mm2, 82.2 +/- 28.4/mm2 (mean +/- SD), respectively, all of which were greater than that in normal skin by a simple comparison. The results of immunofluorescence microscopy were positive with basic fibroblast growth factor staining in the tissues of pyogenic granuloma, Kaposi's sarcoma and MHE. These facts may morphologically indicate a role of MCs in the angiogenesis of these vascular tumors.

Biopsy, Needle↗

Detection of human papilloma virus type 58 in a case of a perianal Bowen's disease coexistent with adult T-cell leukemia.

A case of Bowen's disease (BD) that appeared in the perianal region of a 65-year-old Japanese woman coexistent with chronic adult T cell leukemia (ATL) is described. Histopathological findings revealed that irregularly arranged tumor cells with atypical nuclei throughout the epidermis, which itself disclosed hyperkeratosis, dyskeratotic cells, and clumping cells. Positive staining for HPV antigens was immunohistochemically seen in several nuclei of the tumor cells. Electron microscopic study of the tumor tissue disclosed virus particles of about 50 nm in diameter form the squamous cells. A positive band at 256 bp was obtained by PCR using HPV-L1 primer. The amplified DNA by L1 primer completely corresponded to that of HPV-58.

Aged↗

Brain stem neural mechanisms for vocalization in decerebrate cats.

In order to characterize the brain stem circuitry that produces vocalization, the activities of brain stem respiratory neurons were recorded extracellularly during vocalization induced by electrical stimulation of the periaqueductal gray in decerebrate cats. After the onset of stimulation, the respiratory rhythm ceases, and a preparatory inspiration is induced. Following this initial inspiration, vocalization characterized by increased activities of the intrinsic laryngeal adductor and the major expiratory muscles is induced. During vocalization, most of the dorsal respiratory group inspiratory neurons increase their firing rates in phase with an increase of diaphragm activity. Inspiratory neurons with a continuous discharge pattern in the rostral ventral respiratory group increase their firing rates to augment intrinsic laryngeal abductor motoneurons and bulbospinal inspiratory neurons in the dorsal respiratory group. On the other hand, most of the bulbospinal augmenting expiratory neurons in the Bötzinger complex cease firing just after the onset of periaqueductal gray stimulation for the remainder of the stimulation period. These results indicate that at least some part of the coordinated activations of intrinsic laryngeal and respiratory muscles during vocalization are mediated via the central respiratory neurons that produce breathing.

Animals↗

Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.

Microtubule-dependent motor, murine KIF3B, was disrupted by gene targeting. The null mutants did not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization. Prominently, the left-right asymmetry was randomized in the heart loop and the direction of embryonic turning. lefty-2 expression was either bilateral or absent. Furthermore, the node lacked monocilia while the basal bodies were present. Immunocytochemistry revealed KIF3B localization in wild-type nodal cilia. Video microscopy showed that these cilia were motile and generated a leftward flow. These data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left-right axis in the node.

Animals↗

Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria.

Mouse kif5B gene was disrupted by homologous recombination. kif5B-/- mice were embryonic lethal with a severe growth retardation at 9.5-11.5 days postcoitum. To analyze the significance of this conventional kinesin heavy chain in organelle transport, we studied the distribution of major organelles in the extraembryonic cells. The null mutant cells impaired lysosomal dispersion, while brefeldin A could normally induce the breakdown of their Golgi apparatus. More prominently, their mitochondria abnormally clustered in the perinuclear region. This mitochondrial phenotype was reversed by an exogenous expression of KIF5B, and a subcellular fractionation revealed that KIF5B is associated with mitochondria. These data collectively indicate that kinesin is essential for mitochondrial and lysosomal dispersion rather than for the Golgi-to-ER traffic in these cells.

Animals↗

Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats.

We have recently shown that long-term, but not acute, treatment with lithium robustly protects cultured CNS neurons against excitotoxicity mediated by NMDA receptors. Since NMDA receptor over-excitation has been strongly implicated in the ischemic brain injury, we examined the effects of chronic lithium treatment on neurological deficit and brain infarct induced by occlusion of the left middle cerebral artery in rats. Subcutaneous injection of LiCl for 16 days significantly improved neurological deficits, including abnormal posture and hemiplegia, measured 24 h after artery occlusion. Importantly, the size of ischemic infarct was reduced by 56% after lithium pretreatment. These results raise the possibility that lithium may be useful for reducing focal ischemia-induced brain damage and neurological abnormalities.

Animals↗