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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 235 records · Page 13Linked to original sources

Efficacy of shitei-to, a traditional Chinese medicine formulation, against convulsions in mice.

The anticonvulsant effects of Shitei-To and its components on maximal electroshock seizures and chemical convulsions were examined. Shitei-To significantly prolonged the latency to bicuculline (2.0 mg/kg, s.c.)-induced clonic convulsions. Repeated treatment with Shitei-To also significantly prolonged the latency to strychnine (1.5 mg/kg, i.p.)- and pentylenetetrazol (90 mg/kg, i.p.)-induced clonic convulsions. On the other hand, Shitei-To had no effect on maximal electroshock seizures. Of the components of Shitei-To, Shitei had almost the same effect as Shitei-To against the clonic convulsions induced by the three chemical agents tested. These findings suggest that Shitei-To has anticonvulsant effects.

Animals↗

Increased group IV cytosolic phospholipase A2 activity in lungs of sheep after smoke inhalation injury.

Increased phospholipase A2 (PLA2) activity was measured in cytosolic fractions of lungs from sheep exposed to smoke from burning cotton or to synthetic smoke consisting of carbon and acrolein, a cotton smoke toxin. Three peaks of PLA2 activity were identified by heparin-Sepharose chromatography. The heparin-nonbinding PLA2 activity was twofold higher in the extracts from lungs exposed to smoke than in normal lungs. This activity was identified as the group IV 85-kDa cytosolic PLA2 (cPLA2). The activities of the forms of PLA2 that bound to heparin did not change after smoke exposure. Those activities showed a pH optimum of 9.0, required a millimolar Ca2+ concentration for full activity, and were inhibited by 5 mM dithiothreitol. One activity eluted at an NaCl concentration typical for group Ib and V PLA2 and had the expected substrate specificity. The other form of lung PLA2 that bound heparin was a group II PLA2. Lung myeloperoxidase activity increased progressively with increased exposure to smoke. cPLA2 was identified in sheep neutrophils. With 30 breaths of smoke exposure, there was an increase in cPLA2 activity without a difference in immunoreactivity on Western blot, indicating that the increased activity was not due to increased amounts of protein. In conclusion, smoke induces increases in resident lung cell cPLA2 activity that is likely responsible for eicosanoid production, leading to lung inflammation and bronchoconstriction.

Animals↗

Expression of interleukin-16 by human epithelial cells. Inhibition by dexamethasone.

Production of chemoattractants by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma and other pulmonary diseases. Recently, interleukin (IL)-16 (lymphocyte chemoattractant factor) was reported to be a potent chemotactic stimulus for CD4(+) T lymphocytes and eosinophils, the types of leukocyte found in the proximity of bronchial epithelium in asthmatic individuals. To test the possibility that bronchial epithelial cells produce IL-16, we analyzed RNA and culture supernatants from the human bronchial epithelial cell line BEAS-2B, using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. BEAS-2B constitutively expressed IL-16 messenger RNA (mRNA) and protein; IL-16 expression was significantly upregulated in a concentration-dependent manner within 24 h by stimulation with histamine, IL-1beta, or tumor necrosis factor (TNF)-alpha whereas interferon-gamma did not significantly increase IL-16. Findings in BEAS-2B cells were confirmed in primary bronchial epithelial cells. Using TA cloning, IL-16 was cloned from BEAS-2B airway epithelial cells. Sequence analysis confirmed its near identity with lymphocyte-derived IL-16. The combination of IL-1beta and TNF-alpha had an additive effect on IL-16 expression. This combination of cytokines also had a priming effect on histamine-induced IL-16 mRNA expression, which was observed within 24 h and which increased to at least 48 h after stimulation. The IL-16 expression induced by histamine and combined cytokines was significantly inhibited by pretreatment with the protein synthesis inhibitor cycloheximide (10 microg/ml). Pretreatment with dexamethasone also significantly suppressed the expression of IL-16, in a concentration-dependent manner. Sputum samples from asthmatic subjects were found to have higher levels of IL-16 than were samples from subjects with other pulmonary inflammatory diseases. These findings suggest that bronchial epithelial cells have the capacity to produce IL-16 after stimulation with histamine, IL-1beta, and TNF-alpha, and raise the possibility that epithelium-derived IL-16 may play a role in recruitment of eosinophils and CD4(+) T lymphocytes in the airways. Downregulation of IL-16 expression by dexamethasone suggests that glucocorticoids may inhibit airway inflammation partly by suppressing the synthesis of inflammatory cytokines including IL-16.

Adult↗

Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.

Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Gene expression of erythropoietin in renal cell carcinoma.

A 57-year-old man with renal cell carcinoma and erythrocytosis showed a high serum level of erythropoietin (EPO). High EPO signal was observed on Northern blot analysis and RT-PCR in the total RNA extracted from the renal tumor. Immunohistochemical staining also demonstrated tumor tissue with high immunostaining of EPO. Nucleotide sequences of EPO cDNA in the tumor were normal. To date, only one report has discussed the nucleotide sequences of a tumor's EPO gene; it showed mutant EPO cDNA in hepatocellular carcinoma tissue. This is the first demonstration of normal EPO cDNA in renal cell carcinoma.

Carcinoma, Renal Cell↗

Various extrahepatic manifestations caused by hepatitis C virus infection.

It has been reported that hepatitis C virus (HCV) causes not only liver disease but also disorders of other organs and tissues. Previously, many HCV-related extrahepatic manifestations have been reported. In this study, we report 2 patients in whom tongue cancer was detected during the treatment of HCV-related liver disease. In one patient, tongue cancer was detected during the treatment of HCV-related liver cirrhosis, and articular rheumatism developed thereafter. The duration of HCV-related liver disease was 10 years. In the other patient, tongue cancer was detected during the treatment of HCV-related hepatocellular carcinoma. This patient had a past history of thyroid disease. The duration of HCV-related liver disease was 6 years. In these patients, the possibility that several conditions incidentally and concurrently developed cannot be denied. However, the conditions described above may be regarded as HCV-related extra-hepatic manifestations. In patients with HCV infection, it is important to examine conditions in organs other than the liver. Careful follow-up is needed.

Aged↗

Mutations of the WT1 gene in childhood nonlymphoid hematological malignancies.

The Wilms' tumor gene WT1, whose loss of function accounts for the genesis of about 10% of Wilms' tumors, is expressed in hematopoietic stem cells and leukemia. By analogy with the relationship between the kidney stem cell and Wilms' tumor, it is probable that WT1 is mutated in leukemia. WT1 mutations have been found in only eight cases of primary leukemia, mainly in acute myeloid leukemia (AML) and rarely in acute lymphoblastic leukemia. However, two other studies have demonstrated the absence of WT1 mutations in leukemia. To determine if WT1 mutations are associated with leukemias, we screened childhood nonlymphoid malignancies for WT1 mutation. WT1 mutations were found in 6 of 46 (13%) AMLs, but not in other nonlymphoid hematological malignancies. In addition, the presence of WT1 mutations in AML caused by chromosomal translocations suggests that mutations of WT1 may lead to the progression of leukemia.

Child↗

The utility and limitations of an ultrasonic miniprobe in the staging of gastric cancer.

To determine the utility and limitations of an ultrasonic miniprobe (UMP) in the staging of gastric cancer, we evaluated 46 patients who underwent endoscopic ultrasonography (EUS) using an UMP and who were histologically determined to have gastric cancers. In every case, UMP findings were compared with histopathological findings after treatment. The total accuracy of UMP relative to the depth of tumor invasion was 71.7% (33/46 cases). Accuracy with respect to T1-m tumor diagnosis was 75.7% (22/29 cases), and for T1-sm, 76.9% (10/13 cases), but accuracy for T2 tumor diagnosis was low, due to ultrasound attenuation. When the analysis was carried out based on the size of tumor, the accuracy for UMP was 50.0% (9/18 cases) for all tumors over 20 mm and 85.7% (24/28 cases) for all tumors smaller than 20 mm. We conclude that UMP is suitable for investigation of tumor extension when the lesion is superficial and/or small gastric cancers which do not cause ultrasonic attenuation, but not when the tumor is large or located in certain sites, although conventional EUS is useful in some of these cases.

Aged↗

[Molecular mechanisms of the pathway formation in the fetal rat cerebral neocortex].

Neural cell adhesion molecules (NCAMs), L1 and TAG-1, which are prominently expressed in the developing nervous system, have been shown to promote axonal growth and bundle formation of central neurons in vitro. In the cerebral neocortex of fetal rats, immunoreactions of L1 and TAG-1 were specifically localized on thalamic afferent axons and cortical efferent axons, respectively. L1-bearing thalamocortical axons preferentially extended in the subplate of the cortical anlage where neurocan, a brain-specific chondroitin sulfate proteoglycan (CSPG), was prominently expressed. In contrast, cortical efferent axons immunoreactive for TAG-1 did not enter the subplate and run in the intermediate zone where neurocan expression was less abundant. In addition, TAG-1-bearing axons extensively invaded regions expressing another type of brain-specific CSPG, phosphacan. In the cell culture system, neurite outgrowth of TAG-1-transfected PC 12 D cells was remarkably inhibited on the neurocan substrate, while the outgrowth on phosphacan substrate was significantly promoted. Although both L1 and TAG-1 have been reported to bind both neurocan and phosphacan in vitro, interactions between NCAMs and CSPGs in vivo indicate more complicated patterns than previously thought. Thus, the present results suggest that various patterns of functional correlation between NCAMs and CSPGs play important roles in the pathway formation of the rat cerebral neocortex.

Animals↗

[Hepatic arterial infusion of low-dose cisplatin, 5-fluorouracil for hepatocellular carcinoma with tumor thrombi in the portal vein].

Hepatic arterial infusion of low-dose CDDP (10 mg/day), 5-FU (250 mg/day) was performed in 5 unresectable hepatocellular carcinoma (HCC) patients with tumor thrombi in the trunk and/or the first branch of the portal vein. Infusion chemotherapy was continued for five days, then discontinued for the subsequent two days. This procedure was performed repeatedly for at least three weeks. Decrease in the serum levels of the alpha-fetoprotein after the treatment was found in 3 of 4 patients. In one patient, the size of the primary tumor decreased 92%. In two of five patients, the tumor thrombi in the portal vein disappeared, or decreased in size. Side effects of the chemotherapy included liver functional disorder (Grade 3; 1 case), thrombocytopenia (Grade 3; 1 case, Grade 2; 1 case), and leukopenia (Grade 2; 1 case). The present protocol proved to be effective and applicable for patients with advanced HCC associated with severe cirrhosis.

Aged↗

[Percutaneous microwave coagulation therapy for hepatocellular carcinoma].

We performed percutaneous microwave coagulation therapy (PMCT) for 34 hepatocellular carcinoma (HCC) patients, including 18 primary and 16 recurrent HCC ones. Cumulative 1, 2-, 3- and 4-year survival rates of primary HCC patients were 94, 78, 78% and 62%, respectively, while those of recurrent HCC patients were 100, 79, 62% and 41%, respectively. There were no differences between groups. In both groups, local recurrence was found in about 50% of patients. The mean tumor size (diameter 2.6 +/- 0.6 cm) of patients with local recurrence was relatively larger than that (2.2 +/- 0.6 cm) of patients without local recurrence (p = 0.081). Seventeen of 27 patients with moderately or poorly differentiated HCC had local recurrence, while none of patients with well-differentiated HCC did (p = 0.005). Subsequently, local control failure led some patients to have progressive diseases such as multiple intrahepatic metastasis, tumor thrombi in the portal vein, and distant metastasis. From these findings, PMCT should be performed only for well-differentiated HCC less than 2 cm in diameter. If the patients with moderately or poorly differentiated HCC larger than 2 cm in diameter cannot tolerate hepatic resection because of their poor hepatic functional reserve, PMCT should be performed in combination with other non-surgical treatment modalities.

Aged↗

Liu-Jun-Zi-Tang, a kampo medicine, promotes adaptive relaxation in isolated guinea pig stomachs.

Some patients with dysmotility-like functional dyspepsia present impaired reservoir functions such as gastric adaptive relaxation. A traditional Chinese herbal medicine, Liu-Jun-Zi-Tang, has been identified as an effective drug against dyspeptic symptoms and is widely used for therapy in such patients. In this study, we examined the effects of this drug on the gastric adaptive relaxation in isolated guinea pig stomachs. The changes in intragastric volume and pressure were recorded in the presence of atropine and guanethidine. Gastric adaptive relaxation was induced by luminal distention. Liu-Jun-Zi-Tang (100 mg/ml) induced gastric adaptive relaxation at a lower intragastric pressure and increased the % volume of the gastric adaptive relaxation and the absolute intragastric volume. Metoclopramide (2 mg/ml), trimebutine (6 mg/ml) and cisapride (2 mg/ml) did not affect gastric adaptive relaxation. It was inhibited by means of the incubation of the stomach with NG-nitro-L-arginine (100 microM). Liu-Jun-Zi-Tang (100 mg/ml), but not gastroprokinetics overcame the effect of NG-nitro-L-arginine. These results suggested that Liu-Jun-Zi-Tang promoted gastric adaptive relaxation. This effect might, at least in part, contribute to the symptom relief in patients with functional dyspepsia.

Adaptation, Physiological↗

[Epidural anesthesia for cesarean section in a patient with dilated cardiomyopathy (DCM)].

A 23-year-old patient with dilated cardio myopathy (DCM) was scheduled for a cesarean section. We inserted an epidural catheter at the L 2/3 interspace and injected 1.5% lidocaine 6 ml with epinephrine 30 micro g and fentanyl 50 micro g. The analgesic level 15 minutes after injection was achieved up to the eighth thoracic dermatome. Dopamin 5 micro g.kg-1.min-1 was infused simultaneously. Analgesia was sufficient for the surgery, and heart rate and blood pressure were stable throughout the operation. The infant's apgar scores were 9 and 10. Epidural anesthesia is one of the options for cesarean section in pregnant women with DCM.

Adult↗