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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 379 records · Page 21Linked to original sources

Factors responsible for the prolongation of school refusal.

Two hundred and one school refusers (< or =18 years old), excluding schizophrenia, were treated at the Department of Neuropsychiatry, Hirosaki University Hospital between April 1975 and March 1995. Of 56 cases of school refusal, 31 did not improve for more than 2 years (group P), and 25 cases had improved in the degree of school refusal and social impairment (group B). The remaining cases were excluded from the analysis for several reasons. There was no significant difference between groups B and P in age at the first psychiatric evaluation as well as the age of onset of school refusal. The duration from school absence to the first evaluation of group P was significantly longer than that of group B. The duration of school refusal significantly and positively correlated with the duration from school absence to the first evaluation. Introversion and nervousness prolonged the duration of school refusal. The non-presence of volition for school attendance, and a low frequency of school attendance during the 1 month prior to the first evaluation influenced the prolongation of school refusal. The 'duration from school absence to the first evaluation', the 'patient's character', the 'non-presence of volition for school attendance' and the 'frequency of school attendance' influenced the prolongation of school refusal. The introduction of treatment within 10 months of the onset of school refusal is an important factor in preventing the prolongation of the school refusal.

Absenteeism↗

Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin.

To clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5-HT) release and 5-HT reuptake activity, hippocampal extracellular 5-HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5-HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5-HT levels. Adenosine and A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), decreased extracellular 5-HT levels, whereas non-selective antagonist, caffeine, and A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased them. When 5-HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5-HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not affect 5-HT levels; however, when A1 receptor was blocked by CPT, 5-HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5-HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5-HT reuptake activity might be modulated by hippocampal A3 receptor.

Adenosine↗

Effect of diabetes on vitamin B6 requirement in experimental animals.

AIM: In the diabetic state, energy must be supplied mainly by amino acids and fat; therefore the metabolic processes are very similar to those of animals fed a high-protein diet. Vitamin B6-dependent enzymes, which are highly involved in amino acid metabolism, are important in diabetics. We investigated vitamin B6 content, and aspartate aminotransferase and glycogen phosphorylase activities, in several tissues of streptozotocin-induced diabetic and control rats. METHODS: The rats were fed a vitamin B6-free diet and administered an equivalent amount of pyridoxine based on body weight. RESULTS: Vitamin B6 content in all tissues examined, except for the liver, was lower in the diabetics than in controls. Aspartate aminotransferase activity was higher in the liver of diabetics than in the controls, but not in the other tissues. Glycogen phosphorylase activity in the gastrocnemius muscle of diabetics decreased to two-thirds of the control level. CONCLUSIONS: These data might indicate that diabetic animals should have a higher intake of vitamin B6 because a diabetic state can lead to a vitamin B6-deficiency.

Animals↗

Periodically fluctuating protein kinases phosphorylate CLOCK, the putative target in the suprachiasmatic nucleus.

We studied nuclear protein phosphorylation in the rat suprachiasmatic nucleus (SCN) and found that a nuclear fraction of the SCN contained histone H1 kinase activity that periodically fluctuated with a diurnal rhythm, reaching a maximum at the midpoint of the light phase and a minimum at the midpoint of the dark phase. A p13suc1-bound fraction from the SCN nuclear fraction also exhibited diurnally fluctuating histone H1 kinase activity. Using in situ kinase assay, three histone H1 kinases, p45PFK, p100PFK, and p200PFK (termed periodically fluctuating protein kinases, or PFKs) were found in the p13suc1-bound fractions. p45PFK exhibited the highest level of light/dark cycle phosphorylation activity fluctuation. p45PFK highly phosphorylated the Ser-Pro-rich region of CLOCK, the putative physiological target. These results suggest that PFKs, especially p45PFK, are involved in circadian clock-related signal transduction and gene expression, through the phosphorylation of target proteins such as CLOCK.

Animals↗

Coexpression of CD9 augments the ability of membrane-bound heparin-binding epidermal growth factor-like growth factor (proHB-EGF) to preserve renal epithelial cell viability.

BACKGROUND: Transfection of renal epithelial cells (NRK 52E) with membrane-associated heparin-binding epidermal growth factor-like growth factor (proHB-EGF) increased renal epithelial cell survival by promoting cell-cell and cell-extracellular matrix interactions. ProHB-EGF has been shown to form a complex in the plasma membrane with the tetraspanin CD9, an interaction that significantly increases the effectiveness of proHB-EGF as a juxtacrine mitogenic agent. METHODS: We examined whether the coexpression of proHB-EGF and CD9 would increase renal epithelial cell survival. CD9 was stably transfected into NRK 52E cells, either alone (NRKCD9) or together with proHB-EGF (NRKboth). RESULTS: Juxtacrine mitogenic activity of NRKCD9 was no different than in cells transfected with vector alone (NRKvector), but was increased by NRKboth; juxtacrine mitogenic activity by NRKboth was twofold greater than when proHB-EGF was transfected alone (NRKproHB-EGF). When grown in 10% fetal calf serum, growth rates were similar among all transfectants. However, in 1% fetal calf serum, NRKproHB-EGF grew 50% faster than NRKvector or NRKCD9, and NRKboth grew 20% to 50% faster than NRKproHB-EGF at one, two, and three days of culture. NRKproHB-EGF attachment to plastic substratum at one, two, and three hours was 250% greater than that of NRKvector, and NRKboth was 20% to 30% greater than that of NRKproHB-EGF. Coating plates with either poly 2-hydroxyethyl methacrylate or the GRGDTP peptide prevented normal cell-extracellular matrix attachment, and NRKvector or NRKCD9 failed to attach or form cell-cell attachments. NRKproHB-EGF exhibited 300% and NRKboth exhibited 600% greater cell viability under these conditions. Expression of type I and type III collagen mRNA was enhanced similarly in NRKproHB-EGF and NRKboth, but the expression of beta1 integrin was up-regulated only in NRKboth. CONCLUSIONS: Coexpression of proHB-EGF and CD9 may render the renal epithelial cells more resistant to disruption of cell-cell and cell-matrix interactions and could accelerate the re-establishment of these attachments.

Animals↗

Usefulness of postoperative percutaneous cardiopulmonary support using a centrifugal pump: retrospective analysis of complications.

Between January 1992 and December 1997, we employed percutaneous cardiopulmonary support (PCPS) using a centrifugal pump in 25 patients. In 21 of them, PCPS was used postcardiotomy. These patients could not be weaned from cardiopulmonary bypass due to profound ventricular failure. As for the other 4 patients, PCPS was used preoperatively for profound cardiogenic shock, a thrombosed valve, a stuck valve, and pulmonary embolization. Nine patients (43%) were weaned from PCPS (Group 1), and 3 (14%) were discharged from the hospital. The other 12 patients (57%) had perioperative extensive myocardial infarction and could not be weaned (Group 2). The causes of death were bleeding and multiple organ failure (MOF) associated with ventricular failure. The reasons for MOF were perioperative massive transfusion and hepatic congestion caused by sustained ventricular failure. To increase the survival rate, complete hemostasis and prevention of increased central venous pressure by early use of PCPS are necessary.

Acute Kidney Injury↗

Changes in CD4+ T lymphocyte subsets in circulating blood and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis.

The purpose of this study is to determine the changes in CD4+ T lymphocyte subsets in the circulating blood and synovial fluid following filtration leukocytapheresis (LCP) therapy for patients with rheumatoid arthritis (RA). A Cellsorba column packed with polyester fibers was used for the removal of circulating leukocytes. For patients with RA, filtration LCP or sham procedures were performed 3 times with 1 week intervals between procedures. T lymphocyte surface markers in the peripheral blood and synovial fluid were measured by flow cytometry. The proportions of activated CD4+ T cells (CD4+DR+, CD4+CD25+, and CD4+CD71+) and CD4+CD29+ T cells increased significantly in the peripheral blood, but the counts of these cells were significantly reduced in the synovial fluid after 2 treatment sessions in the LCP group. No significant changes were observed in the proportion of these cells in the control group. Our findings suggest that filtration LCP may cause a redistribution of activated T cells from affected joints into the circulating blood.

Arthritis, Rheumatoid↗

Role of pleural lavage cytology before resection for primary lung carcinoma.

OBJECTIVE: To investigate the role of pleural lavage cytology (PLC) in resection for primary lung carcinoma. SUMMARY BACKGROUND DATA: The prognostic significance of PLC before manipulation is still controversial. METHODS: Cytology of pleural lavage immediately after thoracotomy but before any manipulation of the lung was examined in 500 consecutive patients with lung cancer with no pleural effusion who underwent pulmonary resections. Eighteen patients who already had pleural dissemination were excluded from this study. RESULTS: Eighteen of 482 patients (3.7%) had positive cytologic findings. The positivity of PLC was significantly correlated with histology, extension of tumor to pleura, and presence of lymphatic permeation or vascular involvement by tumor. Positive lavage findings were seen only in adenocarcinoma. Because 6.3% of the patients with adenocarcinoma had positive cytologic findings, it is vital to perform PLC before curative resections for lung cancer, especially adenocarcinoma. The 5-year survival rates of the patients having negative and positive lavage findings were 52.9% and 14.6%, respectively. The prognosis of the patients with positive lavage findings was as poor as that of the patients with stage IIIB disease and that of the patients with malignant effusion. CONCLUSIONS: Positive findings on PLC indicate exfoliation of cancer cells into the pleural cavity, which is an essential prognostic factor. In addition, we should regard positive cytologic findings as a subclinical malignant pleural effusion that is pathologic stage T4.

Bronchoalveolar Lavage↗

The role of total parenteral nutrition in the management of patients with acute attacks of inflammatory bowel disease.

The aim of this study was to evaluate the effects of the prolonged duration of total parenteral nutrition (TPN) on the clinical, laboratory, and nutritional parameters and short-term outcome in acute attacks of ulcerative colitis and Crohn's colitis, and the difference in the response to TPN between the two diseases. Twenty-two patients with severely and moderately active ulcerative colitis (8 severe and 14 moderate) and 12 patients with Crohn's colitis were analyzed retrospectively. Eleven of 22 patients with ulcerative colitis were treated with TPN and corticosteroids (TPN group). The remaining 11 patients were treated with corticosteroids alone and hospital meals (oral diet group). Both groups were matched regarding disease severity at pretreatment. The clinical characteristics, and the initial and total dosages of corticosteroids for 3 weeks were similar between the two groups. The authors compared the changes in the clinical, inflammatory, and nutritional parameters and short-term outcome between the TPN and the oral diet groups with ulcerative colitis. The same evaluations were also made for 12 patients with Crohn's colitis who received TPN (CD group). The TPN group did not show any significant improvement in the clinical parameter, inflammatory signs, or nutritional state compared with the oral diet group with ulcerative colitis. The remission rate after 3 weeks of therapy and a colectomy rate also showed no significant difference between the two groups. In contrast, TPN resulted in a disappearance of clinical symptoms and an improvement in both the inflammatory and nutritional parameters in the CD group. Only one of the 12 patients with Crohn's colitis underwent colectomy. TPN induced no additional benefit in corticosteroid therapy in an acute attack of ulcerative colitis. In contrast, TPN may have primary effects on Crohn's colitis.

Adrenal Cortex Hormones↗

Effects of intestinal bacteria on the development of colonic neoplasm: an experimental study.

Effects of intestinal microflora on the development of colonic neoplasm induced by 1,2-dimethylhydrazine (DMH) were observed using conventionalized and gnotobiotic mouse models. The incidence of colonic adenoma in germ-free mice (IQI/jic) (GF), mice conventionalized after DMH injection (Cvz-post-DMH) and conventionalized mice (Cvz, conventionalized before DMH injection) was 74%, 69% and 58%, respectively. The mean number of adenomas per mouse in the three groups was 2.6, 2.0 and 1.4, respectively. However, the adenoma in Cvz was larger than in GF. The incidence of adenoma in mice mono-associated with Mitsuokella multiacida, Clostridium butyricum, Bifidobacterium longum, Clostridium paraputrificum, Escherichia coli and Lactobacillus acidophilus was 68%, 68%, 63%, 50%, 50% and 30%, respectively. However, the adenoma in the Cl. paraputrificum group and the Cl. butyricum group was larger than in GF. Faecal pH in Cvz and the L. acidophilus group was significantly lower than in GF. The deconjugation rate of faecal bile acids in Cvz, the Cl. paraputrificum group and the Cl. butyricum group was significantly higher than in GF. These findings suggested two different effects of microflora on the development of DMH-induced adenoma: either an inhibition of the incidence of adenoma or a promotion of tumour growth. Effects of L. acidophilus may be mediated by faecal pH and effects of Cl. paraputrificum and Cl. butyricum by deconjugated bile acids.

1,2-Dimethylhydrazine↗

Effects of intestinal bacteria on the development of colonic neoplasm II. Changes in the immunological environment.

To study the effects of intestinal bacteria on the development of colonic neoplasm, we have established gnotobiotic mice with a single species of intestinal bacteria. In the previous study, the incidence of colonic adenoma induced with 1,2-dimethylhydrazine (DMH) in the gnotobiotic mice with Lactobacillus acidophilus, gnotobiotic mice with Escherichia coli and germ-free mice were 30, 50 and 74%, respectively. In this study, 7-week-old mice in each group were sacrificed without the administration of DMH to examine the constituents of immuno-competent cells in various mouse organs using flow cytometry. In the gnotobiotic mice, CD3 intermediate interleukin (IL)-2Rbeta positive cells were observed predominantly in the liver. In the gnotobiotic mice with L. acidophilus, Mac-1 positive Gr-1 positive cells were observed predominantly in the colonic lamina propria. The activation of extrathymic T cells in the liver and granulocytes in the colonic mucosa may be related to anti-neoplastic effects of L. acidophilus in this experimental model.

1,2-Dimethylhydrazine↗

Contribution of major histocompatibility complex genes to susceptibility and resistance in Helicobacter pylori related diseases.

BACKGROUND/AIM: Although there have been numerous reports concerning the virulence factors of isolates for investigating the pathogenesis of Helicobacter pylori infection, few studies have been carried out regarding the association of HLA class II genes of the host with H. pylori related diseases. Two published studies have only analysed the HLA DQ locus alone. The aim of this study was thus to determine the association of HLA class II genes (DR, DQ and DP) with H. pylori related diseases using the DNA typing method. METHODS: Fifty-eight patients with H. pylori positive gastric ulcers, 44 patients with H. pylori positive duodenal ulcers, 45 patients with H. pylori positive gastritis and 34 healthy subjects without H. pylori infection were typed for HLA class II genes by means of DNA typing with the polymerase chain reaction-sequence specific oligonucleotide probes method. RESULTS: A negative association with DRB1*1501, DQA1*01021 and DQB1*0602 alleles was noted in all three of the patient groups studied. Compared with the healthy controls, a positive association with DPA1*0201 (P= 0.032) and DPB1*0901 (P=0.005) in gastric ulcers, a positive association with DRB1*0405 (P=0.022) and DQB1*0401 (P=0.044) in duodenal ulcers, and a positive association with DPB1*0901 (P=0.016) in gastritis were observed. A haplotype analysis showed that the association of alleles with H. pylori related disease was with the haplotype rather than with either of the alleles individually. After correction for multiple comparisons, all the significant associations obtained between H. pylori related diseases and HLA class II genes disappeared. CONCLUSIONS: The interplay between host immunogenetic factors, bacterial virulence factors and environmental conditions may thus play a more important role in the outcome of H. pylori infection than immunogenetic factors alone.

Adult↗

Intrafamilial distribution of mutans streptococci in Japanese families and possibility of father-to-child transmission.

The purpose of this study was to investigate the intrafamilial distribution of mutans streptococci in Japanese families using chromosomal DNA fingerprinting with three endonucleases; EcoRI, HindIII and HaeIII. The analysis of 1,908 isolates cultured from the dental plaque of 76 subjects from 20 families (20 married couples and 36 of their children) resulted in the identification of 144 genotypes containing 114 strains of Streptococcus mutans (serotype c, 66.7%; e, 12.5%) and 30 strains of S. sobrinus (d, 13.2%; g, 7.6%). A mean of 1.89 genotypes (from one to four) was harbored in individual subjects, and a mean of 4.10 genotypes from two to seven was harbored in individual families. Among the 70 genotypes found in the children, 36 (51.4%) were in agreement with their mothers and 22 (31.4%) were in agreement with their fathers. The other genotypes (18.6%) did not correspond with the parents. Homologous strains between parents were found in only two couples. This result showed that fathers or others as well as mothers can be sources of transmission. Further, the serotype d, e and g strains showed significantly higher probabilities of transmission than serotype c.

Adult↗

Increase of the cellular growth of old human diploid fibroblasts by radical scavenger: water-soluble protein from broad beans.

There is increasing evidence that free radical scavengers play an important role in the aging process and the control of cellular growth. We purified a free radical scavenging protein, the water-soluble protein (WSP) from broad beans (Vicia faba). In this study, we examined the effect of WSP on cellular growth and in vitro life span in old human fetal lung fibroblasts (WI-38 and PDL 37-40, 78-84% of the maximum life span). Since WSP increased the cellular growth, we also examined the effect of WSP (1.25-5 microg/ml) on cytosolic antioxidant enzyme activities in the old cells treated or not with tert-butyl hydroperoxide (BHP) to elucidate the mechanisms of cell proliferation in the old cells. The cellular growth of old fibroblasts was greatly increased by WSP. In 1.25 and 2.5 microg/ml of WSP, the cell proliferation increased by 32 and 35%, respectively, as compared with controls. The maximum population doubling levels of the cells did not increase. In the cells incubated with BHP, the cytosolic superoxide dismutase activity was returned to its control value by WSP treatment (1.25-5 microg/ml). The cytosolic glutathione peroxidase activity progressively increased with increasing concentrations of WSP. On the other hand, the cytosolic superoxide dismutase activity after 1.25- and 2.5- microg/ml WSP treatment without BHP was increased by 189 and 144%, respectively. Similarly, the cytosolic glutathione peroxidase activity was increased by 67 and 53%, respectively. These results suggest that cytosolic antioxidant activities in old cells can be modulated by WSP treatment. We concluded that there was a correlation between the optimum WSP concentrations for the increase of cellular growth and the WSP concentrations required to exhibit these maximum enzyme activities.

Cell Division↗

Comparison of risperidone and mosapramine addition to neuroleptic treatment in chronic schizophrenia.

There is little information regarding the effects of risperidone addition to neuroleptic treatment in chronic schizophrenia. As a preliminary study, 10 neuroleptic-treated schizophrenic inpatients received risperidone (high 5HT2A/D2 ratio, i.e. the ratio between 5HT2A and D2 receptor occupancy) and mosapramine (low 5HT2A/D2 ratio) in a randomized, single-blind, crossover, add-on study consisting of 8 weeks of treatment each with risperidone and mosapramine. Although both additions resulted in significant, albeit modest, improvement, there was no significant difference in the scores on the Positive and Negative Syndrome Scale for Schizophrenia between risperidone and mosapramine addition. These results suggest that risperidone and mosapramine bring about comparable effects in add-on design. Thus, risperidone with a high 5HT2A/D2 ratio does not seem to be better than mosapramine with a low 5HT2A/D2 ratio when combined with conventional neuroleptics. Further studies including a large number of patients and a double-blind design are needed.

Adult↗

Treatment of post-transfusion graft-versus-host disease with nafmostat mesilate, a serine protease inhibitor.

BACKGROUND: Cytotoxic T lymphocytes from donors are thought to injure the target organs in post-transfusion graft-versus-host disease (PT-GVHD) through perforin-granzyme- and Fas-dependent cell killings. The protease involved is a serine protease, and nafmostat mesilate (NM), a serine protease inhibitor, has been found to inhibit the in vitro allocytotoxicity of the T cell clone established from a patient with PT-GVHD, thus suggesting the usefulness of NM for treatment of PT-GVHD. CASE REPORT: A 47-year-old male with esophageal cancer, who received 3 units of packed red cells and 20 units of platelet concentrates from 5 unrelated donors, was diagnosed as having PT-GVHD on the basis of typical clinical features, HLA typing of the patient and the responsible donor, and a mixed chimera of CD8+ lymphocytes on microsatellite DNA polymorphism analysis. NM was administered to inhibit the activity of the serine proteases, thought to be granzymes; a liver dysfunction and thrombocytopenia with leukocytopenia simultaneously improved. Subsequently, a high-dose methylprednisolone pulse therapy and monoclonal anti-CD3 were administered to reduce the donor's proliferating lymphocytes, which resulted in lymphopenia accompanied by elimination of the donor's lymphocytes and normalization of the CD4/CD8 ratio. However, recurrence of the proliferation of the responsible donor's lymphocytes developed after cessation of NM administration, probably because of excessive immunosuppression caused by steroids and the monoclonal anti-CD3. CONCLUSION: This case indicates that administration of a serine protease inhibitor may improve PT-GVHD symptoms by inhibiting cytotoxic T-cell-mediated killing of target cells in fatal PT-GVHD. Steroids and monoclonal anti-CD3 were probably responsible for the transient clinical improvements. More studies are required, however, on mechanisms to eliminate the donor's lymphocytes.

Benzamidines↗

Flow-cytometric analysis of leukocyte alkaline phosphatase in myelodysplastic syndromes.

The expression of leukocyte alkaline phosphatase (LAP) in neutrophils is reduced in some patients with myelodysplastic syndrome (MDS). We quantitatively assayed for LAP in MDS leukocytes by a flow cytometry based method using a monoclonal antibody raised against human bone alkaline phosphatase. The LAP expression was assayed in blood samples from a group of 46 MDS patients, consisting of 39 patients with refractory anemia (RA), 3 with RA with excess blasts (RAEB), and 4 patients with RAEB in transformation. The percentage of LAP-positive cells was significantly higher in the MDS patients than in the normal subjects and also higher in RA than in RAEB and RAEB in transformation. To investigate the cause of the elevated LAP expression, we measured the serum concentrations of several cytokines. The granulocyte colony-stimulating factor (G-CSF) level was significantly elevated in MDS patients, and the serum G-CSF concentration clearly correlated with the percentage of LAP-positive cells. Thus, the LAP activity in RA is higher than in normal subjects, and G-CSF is thought to be one of the causes stimulating LAP expression in MDS neutrophils.

Adolescent↗