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Biomedical subjects

T Fujioka

Publications and source records attributed to T Fujioka.

At least 55 records · Page 3Linked to original sources

An ellagic compound and iridoids from Cornus capitata root cultures.

An ellagic acid derivative, 3,3'-di-O-methylellagic acid 4-(5"-acetyl)-alpha-L-arabinofuranoside, and two iridoid glucosides, 6alpha-dihydrocornic acid and 6beta-dihydrocornic acid, were isolated from Cornus capitata adventitious roots cultured in Murashige-Skoog (Murashige, T., Skoog, F., 1962. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol. Plant. 15, 473-487) liquid medium containing 10 microM CuSO(4). Three known related metabolites, i.e. stenophyllin H1, dihydrocornin and cornin were also produced in the root cultures. The chemical structures were characterized by analysis of spectroscopic data.

Ellagic Acid↗

Mild prenatal stress enhances learning performance in the non-adopted rat offspring.

The present study was designed to investigate whether mild stress during pregnancy affects offspring behaviors, including learning performance. Prenatal stress was induced by short-lasting, mild restraint stress, which had previously been shown to facilitate the morphological development of fetal brain neurons. Adult offspring whose dams had been restrained in a small cage for 30min daily from gestation day 15 to 17 showed enhanced active avoidance and radial maze learning performance. In addition, the prenatally stressed rats showed weaker emotional responses than unstressed control, as indicated by decreases both in ambulation upon initial exposure to an open field and in Fos expression in the amygdala induced by physical stress. The observed effects of prenatal stress on learning performance and emotional behavior were attenuated by foster rearing by unstressed dams. Fos expression in the hypothalamic paraventricular nucleus following physical stress and corticosterone secretion during physical and psychological stress did not differ between the prenatally stressed and unstressed control rats. From these results we suggest that mild prenatal stress facilitates learning performance in the adult offspring. The enhancement of learning performance appears to be accompanied by reduced emotionality, but not by any apparent alterations in hypothalamic-pituitary-adrenal responses. In addition, the observation of differential behaviors in the adopted and non-adopted animals supports the notion that the postnatal environment modifies the behavioral effects of prenatal stress.

Amygdala↗

A case of agranulocytosis associated with severe acute hepatitis B.

A 29-year-old male patient with acute hepatitis B developed agranulocytosis about 2 months after the clinical onset of the hepatitis. Bone marrow examination showed hypercellularity and maturation arrest of myeloid leukogenesis at the stage of metamyelocyte. Anti-neutrophil antibody was negative. Since the patient did not show spontaneous recovery for 2 months, the patient received granulocyte-colony stimulating factor, but the therapy was a very short course because he had an elevation of temperature and nausea. Sixty-eight days after admission, he was started on lithium carbonate at a dose of 600 mg per day. About 3 weeks later, peripheral granulocyte counts had recovered to normal level.

Journal Article↗

Involvement of insulin receptor substrates in epidermal growth factor induced activation of phosphatidylinositol 3-kinase in rat hepatocyte primary culture.

Short-term incubation of adult rat hepatocytes with epidermal growth factor (EGF) caused tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 when the cells had been submitted to primary culture from 1-18 h. Tyrosine-phosphorylated IRS-1 and IRS-2 bound to the regulatory subunit (p85) of phosphatidylinositol (PtdIns) 3-kinase, thereby activating the enzymic activity. Tyrosine phosphorylation of the IRSs and activation of PtdIns 3-kinase in 3 h cultured hepatocytes both proceeded similarly to the same actions of insulin; the activation was rapid and transient, with peak values at 15-30 s and with similar EC(50)s in the nM range in both cases. A possible involvement of insulin receptors in these insulin-like actions of EGF was excluded by the following three lines of evidence. Insulin caused tyrosine phosphorylation of the insulin receptor beta-subunit but EGF did not. In contrast, the EGF receptor was phosphorylated by EGF, but the insulin receptor was not. The actions of EGF, but not those of insulin, were inhibited by AG1478, a selective inhibitor of EGF receptor tyrosine kinase. Cultured hepatocytes exposed to insulin or insulin-like growth factor-I (IGF-I) for a short period responded to the subsequent addition of EGF, whereas EGF-treated cells responded to insulin. The cells, however, displayed receptor desensitization under the same conditions, that is, no response was observed upon repeated addition of the same agonist, EGF, insulin or IGF-I. Thus, the EGF receptor-initiated signalling was mediated by PtdIns 3-kinase associated with tyrosine-phosphorylated IRSs in short-term cultured rat hepatocytes.

Animals↗

Further evidence for the involvement of insulin receptor substrates in epidermal growth factor-induced activation of phosphatidylinositol 3-kinase.

In accordance with our recent results obtained with cultured rat hepatocytes [Fujioka, T. & Ui, M. (2001) Eur. J. Biochem. 268, 25-34], epidermal growth factor (EGF) gave rise to transient tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-2), thereby activating the bound phosphatidylinositol 3-kinase in human epidermoid carcinoma A431 cells normally abundant in EGF receptors (EGFR) and Chinese hamster ovary (CHO) cells transfected with full-length EGFR. These actions of EGF, although much smaller in magnitude than those of insulin or IGF-I in the same cells, were accompanied by tyrosine phosphorylation of EGFR rather than insulin or IGF-I receptors, never observed in wild-type CHO cells expressing no EGFR, and totally inhibited by an inhibitor of EGFR kinase, AG1478, that was without effect on insulin or IGF-I actions. Recombinant IRS-1 was phosphorylated on tyrosines upon incubation with purified EGFR from A431 cells and 32P-labeled ATP. When CHO cells were transfected with C-terminal truncated EGFR lacking three NPXY motifs responsible for direct binding to phosphotyrosine-binding domains of IRSs, no effect of EGF could be observed. We suggest that tyrosine phosphorylation of IRS-1 or IRS-2 could mediate EGFR-induced activation of phosphatidylinositol 3-kinase in mammalian cells.

Androstadienes↗

A multicenter, double-blind study on triple therapy with lansoprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients.

BACKGROUND: Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers. METHODS: Patients were randomly chosen for the control treatment of LPZ 30 mg twice a day (b.i.d.; Group A-LPZ-only) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d. (Group B-LAC200) and LPZ 30 mg, AMPC 750 mg and CAM 400 mg b.i.d. (Group C-LAC400). All eradication treatments lasted for a period of 7 days. Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment. RESULTS: The eradication rates of H. pylori in the full analysis set were 0% in Group A-LPZ-only, 87.5% in Group B-LAC200 and 89.2% in Group C-LAC400 for gastric ulcer and, 4.4% in Group A-LPZ-only, 91.1% in Group B-LAC200 and 83.7% in Group C-LAC400 for duodenal ulcer. The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2% (95% CI: 84.8-93.7%) and 86.4% (95%CI: 81.5-91.3%) in total in the full analysis set, 89% (95% CI: 84.3-93.7%) and 85.3% (95%CI: 80.1-90.5%) in the per protocol set. The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients (p <.0001 for both). CONCLUSION: A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Biodisposition of FITC-labeled aloemannan in mice.

Biodisposition of FITC-labeled aloemannan (F-AM) with the homogenate from some organs in mice was demonstrated. F-AM was metabolized only by the mucosa from the large intestine into smaller molecules that were effectively absorbed in mice. The homogenate from the other tissues did not affect the metabolism of F-AM. The degraded product (1) of F-AM after incubation with 10% feces homogenate for 24 h was chromatographed on a highly porous polymer and a Sephadex LH-20 column to provide an FITC-degraded fraction (2), which was shown to have a molecular weight of 800 D on Sephadex G-25 gel permeation. Metabolite 2 was examined by physicochemical methods and shown to be a mixture of FITC-hexose and -2 hexose on FAB-MS. An FITC-degraded fraction (3) with a molecular weight of 3 KD was obtained by 6-h incubation with 10% feces homogenate on Sephadex G-25 column chromatography and was shown to be a mixture of FITC-9 and 12 x hexose on TOF-MS.

Adjuvants, Immunologic↗

Antimicrobial susceptibilities of Helicobacter pylori isolates under microaerophilic atmospheres established by two different methods.

The MICs of clarithromycin, amoxicillin, and metronidazole for 150 Helicobacter pylori isolates were determined using the AnaeroPack system and were compared with those determined using a microaerophilic incubator. The MICs of clarithromycin, amoxicillin, and metronidazole determined under both microaerophilic atmospheres were mostly within one twofold dilution for 146 (97.3%), 150 (100%), and 149 (99.3%) of the isolates, respectively.

Anaerobiosis↗

Expression of multidrug resistance associated transporters (MDR1, MRP1, LRP and BCRP) in porcine oocyte.

Transporters such as P-glycoprotein (MDR1), multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP) are associated with multidrug resistance in various carcinoma cell lines. The expression of these molecules has been also characterized in human normal tissues. However, the expression of these molecules in oocyte is still unclear. In order to obtain more insight into the physiological role of these transporters, their expression in porcine oocyte were examined by reverse transcriptase-polymerase chain reaction. MDR1, MRP1 and LRP genes, but not BCRP gene were found to be expressed in porcine oocyte. After the subcloning and sequence analysis of MDR1, MRP1 and LRP genes, the high homology of these transporters were observed between porcine and human gene. These findings suggest that MDR1, MRP1 and LRP play an important physiological role(s) in an oocyte.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Clinical efficacy of leuprolide acetate and combined treatment with estramustine for advanced prostate cancer].

BACKGROUND/PURPOSE: Twenty-two institutes have organized Keio University Prostate Cancer Study Group to study clinical efficacy and safety of Leuprolide acetate (Leuplin) for the treatment of advanced prostate cancer (clinical stage D1 and D2). Cotreatment of Leuplin and Estramustine phosphate disodium (Estracyt) has been performed to investigate its clinical efficacy. MATERIALS AND METHODS: One hundred and two cases of advanced prostate cancer were treated either with Leuplin alone (group I), Leuplin and Estracyt (group II) or Estracyt alone (group III). After 12 weeks treatment, clinical effects against subjective symptoms (pain, voiding difficulty, performance status and body weight), serum testosterone level, tumor size and serum PSA level were examined to investigate short-term effect of each treatment. The treatment had been continued for 24 months and the treatment effects including progression free survival and overall survival were analyzed. RESULTS: Clinical efficacy after 12 weeks treatment were examined among 97 cases (group I; 35 cases, group II; 36 cases, group III; 26 cases). The background of those patients in each group was statistically equal. Treatment effects against subjective symptoms and serum testosterone level statistically revealed no significant difference among 3 groups. Treatment effects against primary tumor, bone metastatic lesion, lymphnode metastatic lesion and serum PSA level were investigated and anti-tumor effect was characterized by total efficacy rate (complete remission rate plus partial remission rate) of each treatment group. Treatment efficacy rates for each lesion and PSA demonstrated no statistical difference among 3 treatment groups. Total efficacy rate of group I, II and III were 88.2%, 84.0% and 78.3%, respectively, which statistically revealed no significant difference. Total efficacy rate of each group after completing 24 months treatment was; group I 80.0%, group II 55.6% and group III 83.3%, which statistically showed no significant difference among 3 treatment groups. The median day for progression free survival of group I, II and III were 661, 731 and 517, respectively. The overall survival rate of group I, II and III after completing 24 months treatment were 77.5%, 83.0% and 72.4%, respectively. Both progression free survival rates and overall survival rates revealed no significant difference among 3 groups. Side effects during 24 months treatment were seen in 8.6% of group I, 47.2% of group II and 26.9% of group III, and these occurrence rates were significantly different among the groups (p = 0.0013). CONCLUSION: Although number of the cases had not been able to continue the treatment for their side effects, the statistical characterization demonstrated that cotreatment of Leuplin and Estracyt had no greater treatment effect than monotreatment of each drug.

Aged↗

[Selection of antibiotics and planning of eradication for H. pylori infection].

There is general agreement that H. pylori should be eradicated in patients with peptic ulcers. But the optimal therapeutical regimen to be used still remains a matter for many investigations. An increase in the prevalence of antibiotic-resistant H. pylori strains has been reported recently. The recommended drugs for the eradication in Japan are clarithromycin (CAM) and amoxicillin (AMPC) because metronidazole (MNZ) is anti-parasites drug in Japan. A total of 392 H. pylori strains in the last twelve years were tested for sensitivity to CAM, MNZ, and AMPC. The Primary resistance of H. pylori to CAM, MNZ, and AMPC were found in 10.2%, 26.5%, and 0.3% strains, respectively. The resistant strains to CAM were gradually increasing in the last few years. The eradication therapies which do not increase antibiotics resistant strains after eradication failure were reported. The recommendation for eradication in patients with peptic ulcer disease includes those with bleeding ulcers. The pretreatment with proton pump inhibitors (PPI) does not influence the success of PPI-based triple therapy in eradicating H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Occurrence of upper gastrointestinal tract disease after Helicobacter pylori eradication].

Helicobacter pylori (H. pylori) infection is recognized to be a pathogen of various gastro-duodenal disease. Eradication therapy of H. pylori reduces the recurrence of gastro-duodenal ulcer, improves gastritis histologicaly, and is suggested to act an certain role in protection against gastric carcinogenesis. Although, several studies show uncomfortable results arise after H. pylori infection was cured. These studies suggest that gastro-esophageal reflux disease (GERD) and gastro-doudenal erosion may increase after successful eradication of H. pylori. Recently, adenocarcinoma of the gastric cardia and esophagus increase in incidence. Reflux esophagitis and Barrett's esophagus are recognized as precancerous lesion of esophageal adenocarcinoma. It is uncertain the association of newly occurrence of GERD after H. pylori eradication and increase of esophageal adenocarcinoma. Although GERD may lead to adenocarcinoma, long term observations is necessary after H. pylori eradication.

Adenocarcinoma↗

[The efficacy and safety of terazosin and tamsulosin in patients with urinary disturbance accompanying prostatic hypertrophy].

Terazosin (TE) and tamsulosin (TA) were allocated randomly to 38 patients who had urinary disturbance accompanying prostatic hypertrophy, and the efficacy and safety of the drugs were examined. Subjective symptoms due to I-PSS were improved significantly in both TE and TA groups. On the other hand, objective symptoms such as the maximum urinary flow and mean urinary flow were improved more in the TE group. TE showed hypotensive and cholesterol-decreasing effects in patients who also had hypertension and hyperlipemia. No unknown adverse reactions were observed in either groups, and the drugs were shown to be highly safe. TE was considered to be useful as the first choice drug for the patients with hypertension and or hyperlipemia and those with severe objective symptoms. TA was considered to be useful for the patients with impaired drug compliance or those with severe subjective symptoms though objective symptoms were not so severe.

Adrenergic alpha-Antagonists↗

[A thyrotoxic myopathy accompanied with unusual muscle symptoms and MRI muscle findings].

We report a patient with thyrotoxic myopathy associated with unusual muscle symptoms. A 29-year-old man developed hyperhidrosis, diarrhea, increase in appetite, and excitability in July, 1999. In August, he experienced muscle stiffness in bilateral lower extremities after maintaining postures such as driving a car or sitting on a chair. He was admitted to our hospital, in January, 2000. On physical examination, goiter was noted. Neurological examination was normal except for proximal muscle weakness. Laboratory test showed elevated free T3 and free T4, decreased TSH. TSH receptor antibody was increased. MRI of lower extremities revealed atrophy of bilateral biceps femoris. Muscle strength increased gradually after an oral administration of thiamazole 30 mg/day, and muscle stiffness disappeared. The clinical features of this patient and differential diagnosis were discussed.

Adult↗

[Eradication therapy of Helicobacter pylori infection].

Helicobacter pylori(H. pylori) infection is recognized to be a pathogen of various gastro-duodenal diseases. Eradication therapy of H. pylori reduces the recurrence of gastro-duodenal ulcer, and improves gastritis histologically. Recently, proton pump inhibitor(PPI) based triple therapy, that combining PPI, clarithromycin, amoxicillin is widely accepted throughout the world, and shows high eradication rate which ranged about 80-90%. In Japan, one week triple therapy is recommended for the treatment of gastro-duodenal ulcer, though it is expected the improvement of recurrent peptic ulcer. In the present studies, the rate of clarithromycin resistant strains has been increased gradually, and this fact may lead to the development of failure of PPI based triple therapy. Another problem is suggested by several studies that gastro-esophageal reflux disease(GERD) may increase after successful eradication of H. pylori. Reflux esophagitis and Barrett's esophagus are recognized as precancerous lesion of esophageal adenocarcinoma, but the association of newly occurrence of GERD after H. pylori eradication and increase of esophageal adenocarcinoma is not clear. Merits and demerits of H. pylori eradication need to be observed carefully over a long term.

Helicobacter Infections↗

[A case of ureterovesical malacoplakia that manifested hydronephrosis].

A 70-year-old woman visited a nearby physician with a chief complaint of fever and was admitted to a hospital with a diagnosis of acute pyelonephritis. After discharge, pyuria persisted and examination revealed an intravesical solid tumor. The patient was referred to this department for close examination and treatment. The right kidney was hydronephrotic. The intravesical tumor that was resected was solid yellowish-white and ranged from the neck of the uterus to both ureteral orifices. In addition, a grain-sized tumoral lesion, was found in the lower part of the ureter and was also resected. There was sclerotic thickening localized to the right intramural ureter, which had a slightly edematous interior. This was considered to be the cause of the hydronephrosis and a ureteral stent was put in place. Pathological diagnosis was given as malacoplakia. With this case, placement of a ureteral stent was chosen based on the findings of a minimal ureteral lesion, a narrow area of scarring in the intramural ureter as a probable cause of hydronephrosis, and a judgement of mild obstruction. A stent is less invasive for patients, but consideration should be given to urinary infection due to long-term placement recurrence of malacoplakia due to the increased risk of infection, and trouble with periodical exchanging of catheters due to aggravated scarring. Absence of pyuria or signs of recurrence after seven months' placement suggests that use of the stent was the best method.

Aged↗

[Glycated LDL].

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Arteriosclerosis↗