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Biomedical subjects

K Togawa

Publications and source records attributed to K Togawa.

At least 37 records · Page 2Linked to original sources

The targeting of the cyclin D1 oncogene by an Epstein-Barr virus promoter in transgenic mice causes dysplasia in the tongue, esophagus and forestomach.

Cyclin D1 in cooperation with its major catalytic partners, cyclin-dependent kinases cdk4 and cdk6, facilitates progression through the G1 phase of the eukaryotic cell cycle, in part through phosphorylation of the retinoblastoma protein. Cyclin D1's oncogenic properties have been suggested by its cooperation with ras or adenovirus E1a to transform cultured cells, as well its overexpression in transgenic mice that leads to breast cancer. Activated by a number of different mechanisms in human cancers, the cyclin D1 gene is frequently amplified in squamous epithelial cancers derived from the head/neck and esophageal regions. In order to study the functional consequences of cyclin D1 overexpression in these squamous epithelial specific sites, we have linked the Epstein-Barr virus ED-L2 promoter to the human cyclin D1 cDNA and utilized this transgene to generate founder lines. This transgene is transcribed specifically in the tongue, esophagus and forestomach, all sharing a stratified squamous epithelium. The transgene protein product localizes to the basal and suprabasal compartments of these squamous epithelial tissues, and mice from different lines develop dysplasia, a prominent precursor to carcinoma, by 16 months of age in contrast to age-matched wild-type mice. This transgenic model is useful in demonstrating cyclin D1 may be a tumor initiating event in aero-upper digestive squamous epithelial tissues.

Animals↗

Unilateral acoustic neuroma in childhood.

Three cases of unilateral acoustic neuroma in childhood that are associated with neither neurofibromatosis type 1 nor type 2 were reported. All three cases had a hearing disorder as an initial symptom. Two of them had a large neuroma and had considerable abnormal findings in neurootological examinations, and one case with an intracanalicular tumor showed a unilateral progressive sensorineural hearing loss that had no response to steroid administration. Surgical removal of the tumor was carried out for these cases. Different approaches were used in each case; suboccipital approach, one-stage suboccipital and middle fossa approach, and middle fossa approach. Although the facial nerve functions were fairly well maintained, hearing preservation could not be attained in all. Papers dealing with this tumor were reviewed, and certain characteristics of cases with acoustic neuroma in childhood were discussed.

Adolescent↗

[Does physical status influence the axillary temperature among junior high-school students?].

The relationship between physical status and axillary temperature was examined in 373 junior high-school students. Axillary temperature was measured with a mercury glass thermometer, twice a day (8:15, 15:45) for a week, 10 minutes taken for each measurement. In addition, body mass index (BMI) was calculated from weight and height. And the subjects were divided into two groups according to the mean value of BMI (19.20 [kg/m2]), i.e., the low BMI group (LB) and the high BMI group (HB). We then compared the axillary temperature between LB and HB. The temperature both in the morning and afternoon was significantly lower in the HB than in the LB (p < 0.01, p < 0.05). In conclusion, a high BMI was associated with a decrease in axillary temperature in junior high-school students.

Adolescent↗

Ser-27, Tyr-10 and Tyr-7 in the alpha-chain of pig stomach H+,K(+)-ATPase as Ca(2+)-dependent phosphorylatable sites by intrinsic and extrinsic protein kinases.

When pig stomach membrane H+,K(+)-ATPase preparations were incubated with [gamma-32P]ATP, Mg2+ and Ca2+, reversible phosphorylation of specific Tyr and Ser residues in the N-terminal alpha-chain of H+,K(+)-ATPase occurred without any detectable phosphorylation in other regions of the alpha-chain. Mild tosylphenylalanyl chloromethyl ketone trypsin treatment followed by reverse-phase column chromatography yielded three radioactive peptide peaks. The first peak contained both Tyr10(32P) and Tyr7(32P) and the second peak contained Tyr10(32P). The third peak contained Ser27(32P) which was also obtained after trypsin treatment of partially purified H+,K(+)-ATPase preparations phosphorylated with protein kinase-C + Ca2+ or protein kinase-A. This is the first demonstration of Ca2(+)-dependent phosphorylation of the alpha-chain of H+,K(+)-ATPase by protein kinases.

Amino Acid Sequence↗

Carotid artery resection for head and neck cancer.

BACKGROUND: Carotid artery resection has been shown to yield a chance of cure in patients with advanced head and neck carcinoma involving the carotid artery. However, the criteria for the identification of those who are vulnerable to neurologic injury after resection have not been established. Interposition grafting may minimize the risk of neurologic morbidity, although it is technically difficult when there is involvement of the internal carotid artery close to the skull base. METHODS: We studied 24 patients with head and neck tumor involvement of the carotid artery. We performed carotid artery resection in 16 of them, including 10 in whom the carotid artery was reconstructed with interposition grafts covered with muscle flaps. When it was thought that the reconstruction would be difficult, positron emission tomography was performed during balloon test occlusion of the internal carotid artery to assess the adequacy of hemispheric collateral blood flow before carotid resection. In one patient with interposition graft, carotid rupture occurred as a result of wound infection, but none of the other patients experienced perioperative death, persistent hemiplegia, or delayed stroke. RESULTS: Twelve patients have survived longer than 8 months, and seven (43.8%) were alive without disease at 12 months after resection, whereas all four patients who could not be treated operatively died within 8 months as a result of local primary tumors. CONCLUSIONS: Carotid artery resection is the only therapy offering any potential for cure or palliation. Positron emission tomography is a rapid quantitative means of determining the cerebral blood flow, particularly when resection is planned without reconstruction.

Aged↗

Induction of intercellular adhesion molecule-1 in human nasal epithelial cells during respiratory syncytial virus infection.

The effects of infection with respiratory syncytial virus (RSV) on expression of intercellular adhesion molecule (ICAM)-1 was determined in vitro in nasal epithelial cell cultures. Functional consequences of changes in ICAM-1 expression were assessed by measuring adhesion of a human leukaemic T-cell line to RSV-infected epithelial cells. Also, adhesion of phytohaemagglutinin-activated tonsillar lymphocytes (TL) to RSV-infected epithelial cells caused a significant increase in interleukin (IL)-4 or IL-5 production. Release of these cytokines was adhesion dependent as non-adherent TL produced significantly less IL-4 or IL-5. However, no significant difference was observed for IL-2 or interferon-gamma (IFN-gamma) production. These observations suggest that RSV-infected epithelial cells may induce T-helper type-2 (Th2)-like cytokines by mucosal lymphocytes during mucosal infection in vivo.

Adult↗

Synthesis and properties of dimeric glycerophospholipid: 2,2'-dotriacontanedioylbis(1-palmitoyl-sn-glycero-3-phosphocholine).

2,2'-Dotriacontanedioylbis(1-palmitoyl-sn-glycero-3-phosphocholine ) was synthesized chemically as a dimeric version of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. Upon sonication in water, the bipolar lipid furnished a planar membrane of about 50 Angstrom thickness with gel-to-liquid crystalline phase transition constants of Tm = 53.4 degrees C, DeltaH = 20.9 kcal/mol, and DeltaS = 64.0 e.u. In an air/water interface, the lipid displayed unique surface pressure-surface area isotherms with a limiting area of 105-190 Angstrom/molecule at 10-20 degrees C. The lipid was a substrate of phospholipase A2 (Naja mocambique), which afforded 1-palmitoyl-sn-glycero-3-phosphocholine and dotriacontanedioic acid as final products.

Buffers↗

Chemoembolization of head and neck cancer with carboplatine microcapsules.

Fourteen patients with malignant tumor in the head and neck region were treated with infusion of carboplatine microcapsules (CBDCA-mc) via percutaneous super-selective catheterization. A microcatheter was advanced into a feeding artery using a coaxial catheter system. Eleven patients had over 30% reduction of the tumor size on CT within 1 month after embolization. Twelve patients had an increased amount of low attenuation tissue in the tumor on CT after embolization, suggesting increased necrosis in the tumor. No definite hematologic toxicity was found. A majority of patients complained of moderate pain in the embolized region immediately after embolization, easily relieved by i.v. analgesics. Chemoembolization using CBDCA-mc may be an effective therapeutic modality in advanced cases of head and neck cancer.

Aged↗

Immunoglobulin as an eosinophil degranulation factor: change in immunoglobulin level in nasal lavage fluid after antigen challenge.

To examine the involvement of immunologlobulins in eosinophil degranulation, we investigated the change in the amount of immunogobulins in consecutive nasal lavage fluid samples obtained after antigen challenge, as compared with the corresponding eosinophil counts and eosinophil cationic protein (ECP) levels. Eosinophil counts and ECP levels increased both during the early and late phases but more markedly during the late phase. The levels of secretory IgA (sIgA) and IgA were prominently increased at 10 min after challenge, but returned to the respective prechallenge levels by 1 h after challenge. In the late phase they increased again. ECP levels were correlated both with cosinophil counts x sIgA levels and with eosinopil counts x IgA levels. Both sIgA/albumin and IgA/albumin ratios decreased in the early phase, due to the increased permeability of postcapillary vessels, but then increased again in the late phase becoming higher than the respective prechallenge levels. In the late phase, both secretory IgA and IgA seemed to be actively produced and released in nasal mucosa, thus causing eosinophil degranulation.

Adolescent↗

The effect of anti-VLA-4 monoclonal antibody on eosinophil accumulation and leukotriene production in nasal mucosa.

Eosinophil derived leukotrienes and platelet activating factor are known to cause nasal swelling. Toxic proteins induce nasal hyperreactivity to non-specific stimuli including histamine. Recent studies strongly suggest that very late activation antigen-4 (VLA-4) on the eosinophil surface plays a prominent role in the recruitment of eosinophils from blood vessels and eosinophil locomotion in inflammatory tissues. To test this hypothesis, we examined the effect of a monoclonal antibody (mAb) to VLA-4 on eosinophil accumulation in nasal mucosa after antigen challenge in a guinea pig model. Here we have demonstrated that the mAb depressed the eosinophil accumulation in nasal mucosa. In addition, we have shown that this mAb also inhibited eosinophil activation and leukotriene production. Our results raise a possibility that eosinophils might be activated during the journey from bloodstream to inflammatory tissues by the adhesion to endothelial cells and fibronectin. VLA-4 might act as a signalling as well as an adhesion receptor on eosinophils.

Animals↗

[The effect of histamine on the adhesion of endothelial cells to eosinophils].

Recent studies have revealed that eosinophils and eosinophil-derived mediators strongly contribute to the onset of nasal swelling and nasal hyperreactivity. The effect of histamine on the adhesion of endothelial cells to 35S-labeled eosinophils and on eosinophil transendothelial migration was investigated. Human microvascular endothelial cells were isolated and cultured from the mucosa of the inferior turbinates of patients with nasal allergy. Histamine caused dose-related enhancement of adhesiveness to eosinophils. Incubation of endothelial cells treated with 10(-5)M and 10(-4)M histamine increased adhesion to eosinophils by a mean of 56.4% (p < 0.05) and 66.0% (p < 0.05), respectively. When eosinophils were incubated with histamine, they did not induce any increase in adhesion to endothelial cells. Preincubation of endothelial cells with anti-ELAM-1 significantly inhibited histamine-induced adhesion, whereas anti-ICAM-1 and anti-VCAM-1 had no inhibitory effect. Histamine did not increase eosinophil transendothelial migration. Histamine is known to be vasoactive, mediating vasodilation and plasma extravasation. In addition, the results of this study raise the possibility that histamine promotes eosinophil adhesion to endothelial cells by increasing ELAM-1 molecules on endothelial cells and promotes nasal inflammatory and allergic reactions.

Adolescent↗

Human cyclin D1 oncogene and esophageal squamous cell carcinoma.

BACKGROUND: Oncogene activation and tumor suppressor gene inactivation have been implicated in the genetic basis of esophageal squamous cell carcinoma (ESCC). Cyclin D1, an oncogene that has a critical role in G1 progression of the cell cycle, has been observed to be amplified in carcinomas of the breast and head and neck, and translocated in parathyroid adenomas and centrocytic lymphomas. METHODS: Established ESCC cell lines were assayed for cyclin D1 amplification and overexpression by Southern, Northern, and Western blot analyses. In addition, cyclin D1 overexpression was determined in primary tumors and adjacent normal mucosa by differential polymerase chain reaction (PCR) and immunohistochemical staining. RESULTS: The authors observed that approximately 50% of ESCC cell lines with cyclin D1 DNA amplification also had RNA and protein overexpression. Related genes, cyclin D2 and D3, were not amplified or overexpressed in these cell lines with rare exception. The cyclin D1 protein was able to associate with the cell-cycle-dependent kinases, cdk4 and cdk6, but not always with proliferating cell nuclear antigen in selected cell lines tested, representing a novel finding. In addition, approximately 50% of primary tumors had cyclin D1 overexpression that was not present in adjacent normal mucosa. Cyclin D1 overexpression based on PCR correlated with enhanced cyclin D1 protein nuclear staining in malignant cells. CONCLUSION: Cyclin D1 is amplified and overexpressed in ESCC and may be important in its molecular pathogenesis.

Base Sequence↗

Reversible phosphorylation of both Tyr7 and Tyr10 in the alpha-chain of pig stomach H+,K(+)-ATPase by a membrane-bound kinase and a phosphatase.

When pig stomach membrane H+,K(+)-ATPase preparations were incubated with [gamma-32P]ATP and Mg2+ with vanadate, 32P was incorporated into the alpha-chain of H+,K(+)-ATPase to a steady-state level of approximately 0.7 mol of phosphotyrosine (Tyr(P))/mol of phosphoenzyme intermediates. The addition of a membrane H+,K(+)-ATPase preparation with Mg2+ accelerated the liberation of 32P from Tyr(P) residues in the alpha-chain. Mild tosylphenylalanyl chloromethyl ketone-trypsin treatment solubilized 32P-containing peptides from the alpha-chain almost completely. A reverse-phase column chromatography of the supernatant gave two peaks of 32P-peptide with similar total radioactivities. The amino acid sequence of both peaks was shown to be Gly-Lys-Ala-Glu-Asn-Tyr-Glu-Leu-Tyr-Gln--, which is consistent with the amino-terminal sequence of the alpha-chain of H+,K(+)-ATPase deduced from cDNA from pig stomach except that the initial Met was absent. The comparison of the recovery of amino acid from each Edman cycle showed that the phosphorylation of Tyr10 occurred preceding the phosphorylation of Tyr7. These data and others suggested the presence of a novel membrane-bound enzyme system to participate in reversible phosphorylation of both Tyr residues in the alpha-chain of H+,K(+)-ATPase.

Amino Acid Sequence↗

Human papillomavirus-16 and -18 replication in esophagus squamous cancer cell lines does not require heterologous E1 and E2 proteins.

Human papillomaviruses (HPVs) are double-stranded DNA viruses that replicate in the nuclei of squamous epithelial cells. HPVs can be classified into high-risk (e.g., types 16, 18, 31, and 33) or low-risk (e.g., types 6, 11, and 30), depending on their association with benign or malignant tumors. We recently described the association of HPV-16 and -18 with esophagus squamous cell cancer. HPV replication was studied in representative cell lines derived from esophagus cancers. HPV-16 and -18 genomes were independently transiently transfected into HCE-4 and HCE-7 cell lines with and without E1 and E2 genes under heterologous promoters. Southern blot analysis demonstrated that these cell lines support viral replication. However, heterologous E1 and E2 are not required for HPV replication. These findings suggest that specific host nuclear factors in esophageal squamous epithelial cells may support HPV replication.

Blotting, Southern↗

Magnetic resonance imaging of cardiac hemangiopericytoma.

We report a patient with hemangiopericytoma, a rare soft tissue sarcoma, involving the left ventricle. T1- and T2-weighted magnetic resonance imaging (MRI) revealed a high signal mass invading the left ventricular wall. A biopsied specimen obtained from the metastatic subcutaneous tumor in the right popliteal fossa showed pathologic findings consistent with hemangiopericytoma.

Adult↗

A novel human papillomavirus sequence based on L1 general primers.

Over 65 human papillomaviruses (HPVs) have been identified. The majority have been isolated on the basis of cloning systems in bacteria. Recently, general consensus or degenerate primers from the L1 region have been used in PCR to identify novel genotypes. In this fashion, we employed general primers in the L1 region followed by DNA sequencing to identify a novel HPV sequence in association with esophageal squamous cell carcinoma.

Amino Acid Sequence↗

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis.

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Adolescent↗