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Biomedical subjects

K Ohtaka

Publications and source records attributed to K Ohtaka.

At least 19 recordsLinked to original sources
PubMed2006

Hypoxia accelerates cancer invasion of hepatoma cells by upregulating MMP expression in an HIF-1alpha-independent manner.

Tumor hypoxia has been reported to induce tumor progression in several carcinomas. Current studies have shown that hypoxia inducible factor-1alpha (HIF-1alpha) is stabilized under hypoxic conditions and transactivates various genes related to cancer aggressiveness. In the present study, we examined whether hypoxia affects cancer invasion in hepatocellular carcinoma. We aimed to solve the molecular mechanism of tumor invasion under the hypoxic condition. We showed that tumor hypoxia accelerated cancer invasion in two hepatoma cell lines. Using Western blot and RT-PCR analyses we demonstrated striking evidence that the expression of HIF-1alpha, ETS-1, MMP-7 and MT1-MMP was strongly upregulated by hypoxic stimulation. To examine whether these invasion-related genes are regulated by HIF-1alpha, we treated hepatoma cells with TX-402, which was reported to repress HIF-1alpha expression. HIF-1alpha expression was strongly repressed by the TX-402 treatment. In contrast, the expression of ETS-1, MMP-7 and MT1-MMP mRNA was not affected by TX-402 treatment. We further established stable transfectants in which HIF-1alpha dominant negative vector was introduced into Hep3B cells (pHIF-1alphaDN). In the pHIF-1alphaDN cells, the expression of ETS-1, MMP-7 and MT1-MMP was not repressed. Moreover, the invasion activity of pHIF-1alphaDN was not altered, compared with that of the mock. In hepatoma cells, we provided evidence that hypoxic stress accelerates cancer invasion by upregulating ETS-1 and the MMP family by an HIF-1alpha-independent pathway.

Carcinoma, Hepatocellular↗
PubMed2004

Observation of millimeter-wave radiation generated by the interaction between an electron beam and a photonic crystal.

We observed directional light emission in the millimeter-wave region when a high-energy (150 MeV) electron beam passes just above a photonic crystal made of polytetrafluoroethylene beads ( approximately 3.2 mm in diameter). The relation between the momentum and the energy of the emitted photons strongly suggests that the observed light is generated by the umklapp scattering process that changes the evanescent waves emitted by the electron beam into observable ones. By comparing the observed spectra with calculated ones based on the photonic band structure, we found that generated photons excite the photonic band modes making them observable as enhanced fine structures in the emission spectra.

Journal Article↗
PubMed2003

Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils.

BACKGROUND: There is no direct evidence for an animal model of Helicobacter pylori induced duodenal ulcer. AIM: In this study we evaluated the roles of bacterial strain and age of experimental animals in induction of duodenitis and duodenal ulcer in Mongolian gerbils after H pylori infection. METHODS: Specific pathogen free Mongolian gerbils were inoculated orally with three bacterial strains (H pylori ATCC 43504, TN2GF4, and K-6, a clinical isolate from a patient with gastric cancer in our clinic). These strains have both the cagA gene and VacA. Five week old gerbils were used to emulate prematurity infection and 14 week old animals were used as mature test subjects. Animals were observed for 12 weeks after inoculation. Interleukin 8 (IL-8) production in gastric epithelial cells (MKN74) after coculture with the H pylori strains was measured by ELISA. RESULTS: Gastritis and gastric ulcers were found in all gerbils infected with the three strains. However, duodenitis and gastric metaplasia were seen more frequently in gerbils infected with TN2GF4 and K-6 strains than in the ATCC 43504 infected or control groups (p<0.05). Superficial duodenal ulcers with severe duodenitis and gastric metaplasia were found in two gerbils inoculated at 14 weeks with the TN2GF4 strain but none at five weeks. The TN2GF4 strain stimulated significantly higher levels of IL-8 than ATCC 43504 and K6 strains (p=0.0039). CONCLUSIONS: When injected into adult Mongolian gerbils, a specific strain (TN2GF4) of H pylori can induce duodenitis with gastric metaplasia and superficial duodenal ulcers. Induction of duodenal ulcer in an animal model fulfills the requirements of Koch's postulates for establishing a role for H pylori as a causative agent.

Age Factors↗
PubMed2001

On-site diagnosis of H. pylori infection by urine.

We have recently developed an on-site diagnostic kit for H. pylori infection using urine (utilizing immunochromatographic method employing a nitrocellulose membrane coated by extracted H. pylori antigen). Accordingly, we investigated its usefulness in 155 consecutive dyspeptic patients using the 13C urea breath test as a gold standard and further compared its performance with two commercially available rapid diagnostic kits that use whole blood (Helisal Rapid Blood, and ImmunoCard H. pylori). As the results, the urine based on-site diagnostic kit provided 95.9% sensitivity and 87.9% specificity with 92.9% accuracy, which were comparable or even better than that of both rapid whole blood tests, suggesting its usefulness in screening of H. pylori infection.

Antigens, Bacterial↗
PubMed2001

Clarithromycin resistance, but not CYP2C-19 polymorphism, has a major impact on treatment success in 7-day treatment regimen for cure of H. pylori infection: a multiple logistic regression analysis.

Mutations in the gene encoding the CYP2C-19 enzyme for PPI metabolism have been shown to enhance the chance for a cure in a H. pylori-positive patients using a two-week dual-therapy regimen involving omeprazole and amoxicillin. However, the impact of CYP2C-19 genetic polymorphism on eradication rates of a one-week triple-therapy regimen has not been examined. In this cohort study, 156 H. pylori-positive peptic ulcer or NUD patients who presented to our university hospital were recruited. They were treated by one-week omeprazole-amoxicillin-clarithromycin therapy. Host and bacterial predictive factors including H. pylori susceptibility and CYP2C-19 genotyping, as well as cure rate for H. pylori infection, were studied. Cure rate was 85.9% (95% CI: 79-91%) on an intent to treat (ITT) basis. By multiple logistic regression analysis, only clarithromycin resistance had a significant impact on treatment success (odds ratio 28.7: 95% CI: 6-172). CYP2C-19 genetic polymorphism was not associated with a significant change in cure rate. These observations indicate only clarithromycin susceptibility, not CYP2C-19 polymorphism, has a major impact on the treatment success when using a seven-day OAC H. pylori treatment regimen.

Amoxicillin↗
PubMed2000

Comparison of the efficacy of 400mg and 800mg of clarithromycin used with lansoprazole and amoxicillin in eradication regimens for Helicobacter pylori infection in a Japanese population.

We conducted a randomized prospective comparative study to determine whether a 1-week lansoprazole-amoxicillin-clarithromycin (LAC) regimen with 800 mg of clarithromycin a day was more effective such a regimen with 400 mg daily in the Japanese population. One hundred and seventy-five Helicobacter pylori-positive patients were randomly assigned to receive one of two different 7-day regimens, one with clarithromycin 400 mg (LAC 400 regimen) and the other with clarithromycin 800 mg (LAC 800 regimen). The cure rates for both regimens were similar, although adverse effects were significantly more frequent in the LAC 800 regimen, suggesting that 400 mg of clarithromycin may be sufficient in our patient population.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Insufficient diagnostic accuracy of imported serological kits for Helicobacter pylori infection in Japanese population.

Although there are many reports of the high diagnostic accuracy of commercially available serologic kits for Helicobacter pylori infection in Western countries, they rarely has been investigated in oriental population. Accordingly we examined their usefulness in 492 Japanese patients with dyspeptic symptoms. Diagnostic accuracy of 4 imported serologic kits (HEL-p TEST, HM CAP, G.A.P IgG, Helico G2) was investigated using the (13)C-urea breath test as the gold standard. When intermediate results were excluded, the sensitivity, specificity and accuracy of these serologic tests ranged from 88.6% to 97.8%, 67.9% to 85.9%, and 87.9% to 91.4%, respectively, which were comparable with reported median accuracy in the Western population. However, there were many intermediate results in these tests, ranging from 5.3% to 23.0%. Their usefulness seemed to be limited in our patient population because of the large number of intermediate results.

Adult↗
PubMed1996

Role of extracellular matrix on colonic cancer cell migration and proliferation.

A simplified method to quantitatively analyze the migration and proliferation capacity of a colonic cancer cell line (SW837) in vitro was developed. The objective of this study was to evaluate the role of the extracellular matrix in colon cancer metastasis. We used this model to investigate the effects of the extracellular matrix components collagen type I and type IV, laminin, and fibronectin on the migration and the proliferation of cancer cells. Migration was fastest on laminin and slowest on collagen type I. Further, proliferation was highest on laminin of all extracellular matrices groups studied. Therefore, it is concluded that laminin had pronounced effects on migration and proliferation of SW837 cells. These findings suggest that the composition of the extracellular matrix plays an important role in the mechanism of metastasis of colon cancer cells.

Cell Division↗
PubMed1995

A direct involvement of the central nervous system in hypophagia and inhibition of respiratory rate in rats after treatment with O,O,S-trimethyl phosphorothioate.

O,O,S-Trimethyl phosphorothioate (OOS-TMP) is known to induce unique symptoms, which are characterized by hypophagia, progressive weight loss, and hypothermia. To determine whether there is the possibility of a causal relationship between these toxic symptoms and a direct action of OOS-TMP on the central nervous system, we investigated the development of these symptoms in Fischer 344 female rats after oral or intracerebral treatment with OOS-TMP. Oral administration of OOS-TMP at 20 mg/kg induced marked hypophagia, progressive weight loss and hypothermia. Moreover, inhibition of respiratory rate was observed immediately after treatment. It lasts during the entire experimental period. Profound hypothermia below 34 degrees C was observed more frequently in the rats, which became hypercapnic (PaCO2 > or = 50 mmHg). In contrast, administration of OOS-TMP at 20 mg/kg (as much as the oral dose) into the cerebral lateral ventricle succeeded in inducing hypophagia, progressive weight loss and lowered respiratory rates. On the other hand, by this route of administration, OOS-TMP at 20 mg/kg failed to induce hypothermia, hypercapnia and lung injury. The present results suggest that hypophagia and inhibitions of respiratory rate are attributable to the direct action of OOS-TMP on the central nervous system, while other symptoms are associated with lung injury.

Administration, Oral↗
PubMed1994

[Pharmacokinetics of isosorbide dinitrate studied by the extrapolation model].

To make a pharmacokinetic model of isosorbide dinitrate (ISDN), we infused ISDN at 1, 10 or 30 micrograms.kg-1.min-1 into anesthetized rabbits and measured concentrations of ISDN and its metabolites (2-ISMN and 5-ISMN) in plasma, urine and bile. We found the concentration gradient of ISDN between arteries and veins and between the ascending aorta and femoral artery. These concentration gradients may occur due to metabolism and accumulation of ISDN in many organs and tissues, let alone the vascular endothelium. There was no significant difference in plasma concentrations of ISDN or its metabolites between the hepatic vein and femoral vein. It seems that ISDN is metabolized in various organs and tissues. By ISDN infusion of more than 10 micrograms.kg-1.min-1, the plasma concentration of ISDN showed a pronounced increase. It appears that there is metabolic saturation of ISDN. Using these informations, we extrapolated the model to human and the estimated values were compared with observed values to determine the validity of the extrapolation model. There was no remarkable differences between the estimated values and observed values. This suggests the validity of the model. The plasma concentrations of ISDN, estimated by this extrapolated model, showed a linear increase (Y = 30X) with the flow rate range of 0.2-5.0 micrograms.kg-1.min-1, when the metabolic rate was normal. With ISDN infusion of more than 5.0 micrograms.kg-1.min-1, the plasma concentrations of ISDN showed a pronounced increase. In the conditions of impaired metabolism, the plasma concentrations of ISDN increase exponentially.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Patients with calcinosis cutis in National Leprosarium Matsuoka Hoyo-En].

As of the year 1991 there were 358 leprosy patients in National Leprosarium Matsuoka Hoyo-En, including 223 patients (62.3%) who had received the injections of chaulmoogra oil before. Calcinosis cutis caused probably from the injections was noted on 73 patients (32.7%): 67 lepromatous and 6 tuberculosis cases. It has never been reported before that the T type patient suffering from calcinosis cutis was observed in the cases of the chaulmoogra oil injection in Japan. The detectable positions of calcinosis cutis were mostly at the injected sites, that is, outside the right brachium followed by bilateral-branchia and crura. In the group of patients with calcinosis cutis, the anti-PGL antibody was negative for the most part. Urinalyses, peripheral blood figure analyses, histopathological tissue examinations of calcium deposition, X-ray diffraction patterns, differential thermal and gravitational analyses, and chemical analyses were performed on all patients with this disease. Further, as the result of this study six patients with calcinosis cutis caused by sulpyrine was also found. The major component of the deposit by the drug was calcium phosphate. These calcinosis cutis were considered to be of trophopathic calcinosis based on the disorder of subcutaneous tissue due to the injections of respective drugs: chaulmoogra oil and sulpyrine.

Calcinosis↗
PubMed1992

School refusal in Japan.

In Japan, school refusal began to attract the attention of psychiatrists from about 1960, and has been one of the main focuses of contemporary child and adolescent psychiatry because of the increase in the number of patients. It is now one of the most popular diagnosis in the clinical practice of child and adolescent psychiatry in this country. School refusal, however, is not listed as a diagnostic classification of a syndrome or disease in such international classifications of psychiatry as the ICD-9, ICD-10 draft, DSM-III, or DSM-III-R. It is an important task for child and adolescent psychiatry in Japan to determine the position of school refusal in relation to the international diagnostic standards. In this paper, (1) We described the actual conditions of school refusal in Japan. (2) We argued that it was reasonable and clinically useful to retain the concept of school refusal as a clinical entity unique to Japan.

Adolescent↗
PubMed1991

Effect of controlled mechanical ventilation without positive end-expiratory pressure on right ventricular function after coronary artery bypass graft surgery.

To evaluate the changes in right ventricular function during controlled mechanical ventilation (CMV) without positive end-expiratory pressure (PEEP) and during spontaneous breathing, we compared right ventricular ejection fraction (RVEF), right ventricular end-diastolic volume index (RVEDVI), and right ventricular end-systolic volume index (RVEDVI) using a thermodilution technique after coronary artery bypass graft surgery. Patients were divided into two groups on the basis of changes in RVEDVI from CMV to spontaneous breathing: group U (n = 6) consisted of patients whose RVEDVI increased during spontaneous breathing compared with mechanical ventilation, group D (n = 3) consisted of patients whose RVEDVI decreased during spontaneous breathing compared with mechanical ventilation. PVRI values during CMV in group D were significantly larger than those in group U. Patients in group U showed no increase in RVEDVI, or decrease in RVEF during CMV without PEEP. However, the remaining 3 patients in group D showed an increase in RVEDVI and a decrease in RVEF during CMV. Mean PAP, RAP, RV systolic pressure, RV end-diastolic pressure, PWP, HR, and mean arterial pressure in both groups were comparable, and showed no significant difference at each of the measured points by 24 hrs postoperatively. Then, RVEF, RVEDVI and RVESVI measured by thermodilution technique is useful in evaluating ventricular function at bedside in ICU.

Journal Article↗