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Biomedical subjects

K Fukao

Publications and source records attributed to K Fukao.

At least 109 records · Page 6Linked to original sources

Transient P300 abnormality of event-related potentials following unilateral temporal lobectomy.

Event-related potentials (ERP) were recorded during auditory oddball tasks for a patient prior to and soon after left anterior temporal lobectomy. The N100 amplitude decreased bilaterally although the latency did not change after the lobectomy. The P300 amplitude decreased in the left hemisphere at 1 and 2 weeks after surgery, then recovered to the pre-operative level at 4 weeks. These findings suggest that the medial temporal structure participates in the generating system of P300.

Adult↗

Influence of partial hepatectomy in dogs on trimethadione metabolism and microsomal monooxygenases.

1. The recovery of trimethadione (TMO) metabolism and its association with liver weight and the activity of TMO N-demethylase have been reported in rat following partial (68%) hepatectomy. In the present study, we examined the effect of liver regeneration on hepatic P450 isozymes and TMO metabolism in dog. 2. The ratio of dimethadione (DMO), being the only TMO metabolite, to TMO at 2 h after i.v. injection of TMO (4 mg/kg) fell to 80% of that in the preoperative animals by 24 h after hepatectomy. The DMO/TMO ratio gradually recovered from days 7 to 14, and by day 21 after hepatectomy it had increased to about 25%. At 28 days post-hepatectomy the ratio had returned to preoperative levels. 3. The activity of benzphetamine N-demethylase, TMO N-demethylase, p-nitro-anisole O-demethylase and aniline hydroxylase increased 3 days post-hepatectomy, exhibiting levels 4.77, 3.45, 1.51 and 1.91 times greater respectively than that of the preoperative liver in the same animal. Two weeks post-hepatectomy these activities had returned to normal. The activity of the 16 beta- and 2 beta-hydroxylation of testosterone was unchanged. However, the activity of 6 beta-hydroxylase decreased 7 days post-hepatectomy, while 16 alpha-hydroxylation had increased at 3 and 7 days post-hepatectomy compared with controls. 4. The changes in liver weight were nearly restored to preoperative levels 7 days post-hepatectomy. 5. Although the P450 content was unchanged from days 1 to 7 post-hepatectomy, it had decreased by 30% at day 14 and by 20% at day 28. The P4502B11 content 3, 7 and 14 days post-hepatectomy had increased 8, 10 and 2 times respectively, while the P4503A12 content at 7 and 14 days decreased by 30 approximately 50% compared with that of the pre-operative liver. 6. The data presented above do not reveal any relationship between P4502B11 induction and liver regeneration. The reason for such a change is unknown, therefore further investigation needs to be carried out.

Animals↗

[Intra-arterial 5-FU/intra-venous MTX therapy for metastatic liver lesions].

We have performed intra-arterial 5-fluorouracil (5-FU)/intra-venous methotrexate (MTX) therapy for 4 patients with multiple metastatic liver tumors at out-patient clinic. Primary lesions were of the stomach (one patient, synchronous) and colon (3 patients, two were synchronous and one was metachronous). 5-FU (250-350 mg/day) was continuously infused for two weeks into the hepatic artery through the reservoir using the Baxter Infuser (multi-day type). MTX (100 mg/m2) was infused into the peripheral vein on days 1, 8 and 15. Leucovorin calcium (15 mg) was orally administered three times after MTX infusion. All patients partially responded, and no remarkable side effect was detected. We propose that this new combination therapy, that is intra-arterial 5-FU and intra-venous MTX for metastatic liver cancer, can be useful and safe even for out-patients.

Administration, Oral↗

[Abnormal expression of E-cadherin in human pancreatic carcinoma cell lines].

Nineteen human pancreatic cancer cell lines were analyzed for possible abnormal mRNA and/or protein expression of the E-cadherin. Five lines showed no or markedly reduced expression of the E-cadherin, and protein was absent. In 9 lines, mRNA was positive but protein distribution was abnormal, i.e. diffusely positive in cytoplasm instead of membrane, or mixed distribution to membrane and cytoplasm. These 14 cell lines with abnormal E-cadherin expression grow in isolated fashion or loose sheet formation, indicating the loss of cell-cell adhesion system. These findings that the strong relation between E-cadherin abnormalities and loss of physical cell-cell interaction may explain the extensively poor prognosis of the patients with pancreatic carcinoma.

Cadherins↗

[The practical benefits of magnetoencephalography in comparison with electroencephalography in a patient with epilepsia partialis continua].

A concurrent recording of electroencephalography (EEG), magnetoencephalography (MEG) and electromyography (EMG) was carried out in a patient with epilepsia partialis continua. He had continuous clonic jerks in his right hand and fingers. The EMG electrodes were placed on the thumb of his right hand. We observed numerous MEG spikes in the left central region and about half of them were accompanied by EMG potentials with a latency of about 20 msec. The EEG spikes appeared less frequently, had low amplitudes, and had unclear morphologies and further, no clear association with EMG potentials. MEG spikes were more reliably associated with individual jerks, exemplified by EMG potentials, than the EEG spikes. The MEG spikes were sharper than EEG spikes and were about 20 msec wide. The intracranial dipole localization of the MEG spikes was estimated by overlaying the calculated generator sites on magnetic resonance images. It was found that the spikes converged along a line, presumably the central sulcus. The practical benefits of the MEG as a diagnostic tool in epilepsy are illustrated.

Adult↗

[Whole abdominal irradiation for peritoneal dissemination of alimentary tract cancers].

Between January 1986 and August 1991, 19 patients with alimentary tract cancers complicated by peritoneal dissemination received whole abdominal irradiation combined with intraperitoneal chemotherapy postoperatively. Using a moving-strip technique of irradiation, 12.0 Gy was delivered in three fractions to the entire abdominal contents with partial liver and kidney shielding. The primary tumor sites were the stomach in 12 patients, the colorectum in five, and the gall bladder in two. Nine patients with gross residual disease also received a limited field boost of 30.6 Gy in 17 fractions after completion of treatment to the whole abdomen. None of the patients failed to complete the planned dose despite acute gastrointestinal toxicity (nausea and vomiting, 84%, diarrhea and cramping, 78%) and acute hematologic toxicity (leukocytopenia, 84%, thrombocytopenia, 68%). Our follow-up study revealed that the actuarial one-year survival rate was 28.4% and the median survival time was 9.0 months. Survival rates at one-year for patients with colorectal and gastric cancer were 75.0% and 16.7%, respectively. Patients with gastric cancer (n = 12) had a poorer outcome than those with colorectal cancer (n = 5) in the present study. One reason for this difference may have been the presence of cancerous pleuritis, which was frequently observed in patients with gastric cancer. Therefore, more intensive treatment to prevent cancerous pleuritis seems to be necessary to improve the efficacy of whole abdominal irradiation.

Abdomen↗

Phenotypic analysis of nylon-wool-adherent suppressor cells that inhibit the effector process of tumour cell lysis by lymphokine-activated killer cells in patients with advanced gastric carcinoma.

The causes of down-regulation of cytotoxic immune responses in cancer patients have not been fully evaluated. We previously demonstrated that T-cell-growth-factor-activated peripheral blood lymphocytes (PBL) with the surface phenotype CD8+ CD11b-, from patients with widespread metastasis of gastric carcinoma, inhibited the effector process of lymphokine-activated-killer(LAK)-cell-mediated cytolysis. In this study, we examined suppressor cell activity in freshly prepared PBL from 18 patients with advanced gastric carcinoma, and 10 normal healthy individuals. The suppressor cell activity was assayed by recording whether or not PBL inhibited directly the effector process of LAK cell cytotoxicity. Most of the PBL suspensions from cancer patients showed that they contained a population of cells that can directly inhibit the effector phase of tumor cell lysis of the cytotoxic cells. To analyze further the PBL responsible for the suppression, the cells were passed over a nylon-wool column. Nylon-wool-adherent cells significantly augmented the suppression, while the cells passing through abrogated the suppressive effect. Most nylon-wool-adherent cells from 10 normal healthy controls did not inhibit the cytotoxic reaction. To determine further the suppressor-effector population in nylon-wool-adherent cells, negative-selection studies using CD8-, CD4- or CD11b-coated magnetic beads, and positive-selection studies using CD8- or CD4-coated magnetic beads were performed. Finally the results suggest that the suppressor-effector cells comprise at least two different surface phenotypes: CD8+ T and CD8-CD11b+ cells. The possible role of CD4+ T cells and HLA-DR+ LeuM3+ macrophages as suppressor cells was ruled out in nylon-wool-adherent cells. CD8+ T and possibly CD8-CD11b+ cells apparently suppressed the efferent limb of the antitumor immunity. The selective immune suppression mediated by these cells may partly be concerned with escape mechanisms of gastric carcinoma from the host immune surveillance system.

Adult↗

Deviate P200 and P300 in non-patient college students with high scores on the schizophrenia scale of the Minnesota Multiphasic Personality Inventory (MMPI).

Event-related potentials (ERPs) were examined in 16 college students who had high scores on the Schizophrenia Scale of the MMPI (HSS) but were without a hereditary disposition for major psychiatric disorders. 32 sex- and age-matched college students were used as controls. Subjects whose T scores were higher than 70 were designated the HSS subjects. ERPs were recorded during an auditory oddball task. Although neither the P300 latencies nor the P200 latencies differed between the two subject groups, the amplitudes of P300 to rare stimuli and P200 to frequent stimuli were lower in the HSS subjects than in the controls. These results suggest that deficits, both in the P300-related cognitive function to rare relevant stimuli, as well as matching and/or the comparison process for irrelevant frequent stimuli, may be present in HSS subjects. The HSS subjects, especially those with a combination of P300 and P200 deficits, even though without a hereditary diathesis for schizophrenia, may constitute one type of high-risk group.

Adolescent↗

[Immunohistochemical study of VLA integrins in human gastric carcinoma].

Using an immunohistochemical technique, we investigated expression of collagen receptor VLA-2 integrin and laminin receptor VLA-6 integrin in human gastric carcinoma. The expression of VLA integrins was compared in carcinoma of each histologic type and invasion/growth pattern. VLA-2 and VLA-6 were expressed more weakly in undifferentiated carcinoma than in non-cancerous epithelium. Non-localized invasion was observed in 89% of undifferentiated carcinoma. In differentiated carcinoma, expression of VLA-2 was weak in the mucosal layer. In the submucosal layer, however, VLA-2 expression was significantly different according to the invasion/growth pattern (p < 0.01); weak expression of VLA-2 in the localized invasion type and strong expression of VLA-2 in the non-localized type. VLA-6 was strongly expressed in the mucosal and submucosal layers of the differentiated carcinoma, regardless of the invasion/growth pattern. The present study suggested that VLA-6 contributed to the histologic type and VLA-2 affected the invasion/growth pattern of the gastric carcinoma in varied manners according to the histologic type.

Carcinoma↗

N200 component of event-related potentials in depression.

Event-related potentials (ERPs) recorded during a two-tone discrimination (oddball) task were examined in 36 drug-free depressed patients and 36 control subjects. At remission, the ERPs of 12 of the depressed patients were reexamined. In the depressed patients, although a group difference was not detected in the peak latency and amplitude of N200 to rare stimuli, the mean amplitude for the N200 latency range in the difference waves was smaller than in the control subjects. Mismatch negativity (N2a), which was elicited by rare stimuli, was reduced in amplitude; but N2b may have been evoked to frequent stimuli more in the patients than in the control subjects. Depressed subjects may have a deviance in the fully automatic cerebral mismatch process that is assumed to be related to mismatch negativity and provoke the controlled mismatch detection process (presumed to be associated with N2b) even to nontarget frequent stimuli. These findings were observed during remission; however, there was a tendency for the N2b amplitude to decrease and recover toward the level of the control subjects.

Adolescent↗

Comparison of hepatic drug-oxidizing activity after simultaneous administration of two probe drugs, caffeine and trimethadione, to human subjects.

Pharmacokinetic interactions between caffeine 2 mg/kg and trimethadione 4 mg/kg were evaluated in 10 healthy volunteers. Whether administered alone or together, the total body clearance (CL), the apparent volume of distribution (Vd) and half-life (t1/2) of caffeine and trimethadione were the same, however, there was a weak correlation between the CL of caffeine and trimethadione [alone: r = 0.51 (P < 0.05); coadministered: r = 0.56 (P < 0.05)]. There were also weak correlations between the CL of trimethadione and the area under the serum concentration-time curves (AUC) of theobromine (r = -0.61, P < 0.05), paraxanthine (r = -0.69, P < 0.05) and theophylline (r = -0.60, P < 0.05), when the two drugs were administered alone. After combined administration, the correlation between the CL of trimethadione and the AUCs of the metabolites of caffeine were as follows: theobromine r = -0.63 (P < 0.05); paraxanthine r = -0.68 (P < 0.05); theophylline r = -0.65 (P < 0.05). These findings suggest that caffeine and trimethadione metabolism in healthy subjects is mediated by only in part by a form(s) of P450 enzymes involved.

Adult↗