Biomedical subjects

Y Kawata

Publications and source records attributed to Y Kawata.

At least 73 records · Page 4Linked to original sources

PubMed1997

Biphasic effects of carbamazepine on the dopaminergic system in rat striatum and hippocampus.

To clarify the effects of carbamazepine (CBZ) on dopamine (DA) release and their metabolism, the extracellular and total levels of DA, its metabolites (DOPAC and HVA) and precursor, 3,4-dihydroxyphenylalanine (DOPA) in the striatum and hippocampus were studied. DA re-uptake and DOPA accumulation in the striatum and hippocampus, and monoamine oxidase (MAO) activities were also determined. After acute and chronic administrations of CBZ, the plasma concentration of CBZ associated with therapeutic activity increased the extracellular and total levels of all substances determined, whereas supratherapeutic concentration of CBZ decreased extracellular and total levels of all substances. Neither therapeutic nor supratherapeutic concentrations of CBZ affected MAO-A nor -B activities, nor DA re-uptake. DOPA accumulation caused by NSD1015 was inhibited by therapeutic and supratherapeutic concentrations of CBZ. These results suggest that a therapeutic concentration of CBZ enhances DA turnover, whereas a supratherapeutic concentration of CBZ inhibits DA turnover. These effects of CBZ on dopaminergic systems may be, at least partially, involved in the mechanisms of action of CBZ.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Effects of non-toxic and toxic concentrations of phenytoin on monoamines levels in rat brain.

To clarify the mechanisms of the antiepileptic activity of phenytoin (PHI), the effects of PHT on extracellular and total levels of monoamines (dopamine and serotonin), in rat striatum and hippocampus were studied. The plasma concentrations of PHT associated with therapeutic activity did not affect striatal and hippocampal extracellular levels of monoamines, whereas supratherapeutic concentrations of PHT decreased striatal and hippocampal extracellular levels of monoamines, in a concentration dependent manner. Toxic concentrations of PHT produced generalized seizures 'paradoxical intoxication' and an initial drastic decrease in striatal and hippocampal extracellular levels of monoamines before seizure onset, whereas the extracellular monoamines levels increased after seizures. In addition, the therapeutic concentrations of PHT did not affect monoamine turnover, whereas supratherapeutic concentrations of PHT inhibited monoamine turnover. These results suggest that monoaminergic transmission may not be involved in the antiepileptic mechanism of action of PHT, and that dysfunction of monoaminergic transmission can produce generalized tonic-clonic convulsions. Thus, the present study suggests that 'Paradoxical Intoxication' induced by toxic concentrations of PHT, at least partially, can be mediated by hypo-monoaminergic function in the brain.

Animals↗

PubMed1997

Effects of adenosine receptor subtypes on hippocampal extracellular serotonin level and serotonin reuptake activity.

To clarify the effects of adenosine receptor subtypes (A1, A2, and A3) on hippocampal serotoninergic function, hippocampal extracellular serotonin (5-HT) levels were determined by in vivo microdialysis in freely moving rats under various conditions. Both adenosine and an adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine, decreased extracellular 5-HT levels, whereas an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT), and caffeine increased these levels. A selective A2A receptor agonist (CGS-21680), an adenosine A2 receptor agonist (PD-125944), an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and an adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA), did not affect extracellular 5-HT levels. When the adenosine A1 receptor was blocked by CPT, the hippocampal extracellular 5-HT level was increased by adenosine, CGS-21680, and PD-125944, and decreased by caffeine, DMPX, and APNEA. When both adenosine A1 and A2 receptors were blocked by CPT and DMPX, the extracellular 5-HT level was decreased by adenosine, caffeine, and APNEA. The hippocampal extracellular 5-HT level was not affected by administration of APNEA alone, but was decreased by this agent when the adenosine A1 receptor was blocked, irrespective of whether the adenosine A2 receptor was functional. These inhibitory effects of adenosine, caffeine, and APNEA on extracellular 5-HT levels, during both adenosine A1 and A2 receptor blockade, were inhibited by selective 5-HT reuptake inhibitors. These results indicate that the stimulatory effects of the adenosine A2 receptor and the inhibitory effects of the A3 receptor on hippocampal extracellular 5-HT levels are masked by the inhibitory effects of the adenosine A1 receptor.

Animals↗

PubMed1997

Consumption of cow milk and egg by lactating women and the presence of beta-lactoglobulin and ovalbumin in breast milk.

beta-Lactoglobulin and ovalbumin in mature human milk in healthy lactating Japanese women (n = 24) were determined by using an enzyme-linked immunosorbent assay. Subjects consumed > or = +200 mL cow milk/d for 1 wk before the sampling day and exactly 200 mL cow milk on the morning of the sampling day. beta-Lactoglobulin was detected (> 0.1 microgram/L) in breast milk in 15 of the 24 subjects (62.5%), with a maximum concentration of 16.5 micrograms/L. Ovalbumin was detected in only two subjects (8.3%) after the subjects followed their usual diet. beta-Lactoglobulin concentrations were low in the subjects whose cow milk consumption during the entire lactating period was low, even though all subjects consumed the same amount of cow milk before sampling. This result suggests that beta-lactoglobulin concentrations in breast milk are related to long-term consumption of cow milk. Amounts of food antigens in breast milk may be controlled by modifying the daily maternal diet.

Adult↗

PubMed1997

Prognosis and clinical features of intractable epilepsy: a prospective study.

Of the epileptic patients who were treated for > or = 5 years until the end of 1990 and had more than four seizures in 1990, 63 patients had been treated without interruption until the end of 1995. We analyzed their clinical courses from 1990 to 1995 prospectively. More than half the subjects were diagnosed with temporal lobe epilepsy. Twenty cases had presumed etiology, and 32 had neuropsychiatric complications. Of the subjects whose seizures were not controlled with conventional antiepileptic drugs (AED), 11 cases demonstrated significant improvement when new AED; that is, lamotrigine, vigabatrin, clobazam, topiramate, tiagabine or CGP33101 were added. However, 10 patients did not respond to new AED. Presumed etiology, neuropsychiatric complications, multiple epileptic foci in EEG and abnormalities on head CT or MRI were characteristics of the patients whose seizures were resistant to new AED.

Adult↗

PubMed1997

Porphyromonas gingivalis fimbria-stimulated bone resorption is inhibited through binding of the fimbriae to fibronectin.

Our most recent study demonstrated that fibronectin is one of the Porphyromonas gingivalis fimbria-binding proteins. In this present study, we demonstrate with mouse embryonic calvarial cells that P. gingivalis fimbria-stimulated bone resorption is inhibited by human fibronectin. The fibronectin inhibition was dose and culture time dependent and was completely neutralized by antifibronectin antibody. The inhibitory action of fibronectin depended on fimbrial interaction with the heparin-binding and cell-attachment domains in the fibronectin structure.

Animals↗

PubMed1997

Long-term consumption of whey hydrolysate formula by lactating women reduces the transfer of beta-lactoglobulin into human milk.

Food antigens transferred into breast milk sometimes cause an allergic reaction in exclusively breast-fed infants. This study will show whether the intake of a whey hydrolysate formula for lactating women (MOM HA) can reduce the appearance of food antigens in breast milk. Lactating women in the MOM group (n = 12) consumed MOM HA as a substitute for cow's milk and those in the COW group (n = 13) consumed cow's milk for more than 4 months. After the ingestion of 200 mL of MOM HA and cow's milk by the women in the MOM and COW groups, respectively, the first breast milk samples were obtained and beta-lactoglobulin was measured using enzyme-linked immunosorbent assay. The number of subjects with detectable beta-lactoglobulin (> 0.1 ng/mL) in the MOM group was two (17%), which was significantly less than that in the COW group (11 subjects, 85%, p < 0.01). The level of beta-lactoglobulin was also lower in the MOM group than the COW group (p < 0.01). Subsequently, the women in the MOM group consumed cow's milk and those in the COW group consumed MOM HA for one week; then a second sampling was performed. beta-Lactoglobulin was detected in three (25%) and 8 subjects (62%) in the MOM and COW groups, respectively. The level of beta-lactoglobulin was still lower in the MOM group (p < 0.05). The consumption of whey hydrolysate formula by lactating women over a considerable time reduces the transfer of beta-lactoglobulin into their breast milk, and the low level can be maintained even after inadvertent ingestion of cow's milk.

Animals↗

PubMed1997

[Pregnancy and delivery in the patients with spina bifida--report of 5 cases].

BACKGROUND: Because of improvement in the management for life-threatening complications of spina bifida, quality of life in the patient has become better and pregnancy is becoming more common problem in adolescent and adult female patients. In this paper, we reported patients with spina bifida who became pregnant and delivered a baby. METHODS: There were 6 deliveries from 5 patients. Mean patient age at the first pregnancy was 27.6 years (ranged from 26 to 32 years). Four patients had undergone surgical managements before pregnancy, of whom 1 had augmentation cystoplasty. Urological and obstetrical conditions during the pregnancy were analyzed. RESULTS: Upper urinary tract deterioration which was transient, was observed in 3 pregnancies. Serum BUN and creatinine levels remained stable throughout pregnancy in 4 patients. Pyelonephritis complicated 3 of 6 pregnancies. Delivery was vaginal in 4 and by cesarean section in 2. There were 7 obstetrical complications, which consisted of premature labor (2), uterine inertia (2), cephalo pelvic disproportion (2) and hydramnios (1). There were no significant anomalies in the newborns of these patients. CONCLUSION: To achieve successful pregnancy and delivery in the patient with spina bifida, careful urological and obstetrical observation for the potential complications is needed.

Adult↗

PubMed1997

[Clinical findings of neurogenic bladder in patients with Parkinson's disease, multiple sclerosis and spinocerebellar degeneration].

Clinical symptoms, urodynamic findings, and urological treatment of 35 patients with neurogenic bladder dysfunction caused by Parkinson's disease (11 patients), multiple sclerosis (10 patients), and spinocerebellar degeneration (14 patients) were reviewed retrospectively. Most of the patients had a relatively low stage of disease, when they were first seen by their urologists. Chief urological complaints were of irritation in 63.6% of Parkinson's disease and 64.3% of spinocerebellar degeneration cases, compared with obstruction in 80.0% of multiple sclerosis cases. Cystometry revealed underactive detrusor function in 69.2% of the patients with spinocerebellar degeneration but no abnormalities in the patients with Parkinson's disease or multiple sclerosis. Of 34 patients, excluding one patient lost to follow-up, the period of urological management ranged from one to 44 weeks with a mean of 11.0. The final methods of urinary drainage in 34 patients consisted of voluntary voiding in 20, clean intermittent catheterization in 11 including eight by self catheterization, incontinence into diaper in two, and indwelling catheter in one. Five patients were compelled to change urinary drainage method from voluntary voiding to clean intermittent catheterization because of increasing residual volume in four and progressing bladder deformity in one. However, none of them showed the clinical signs of primary disease progression. These findings indicate that in patients with Parkinson's disease, multiple sclerosis, and spinocerebellar degeneration, the urological symptoms can appear even in the early stage of disease. In addition, close follow-up is important in the urological management of neurogenic bladder patients with these diseases, because the disorders of the lower urinary tract may progress regardless of the status of the primary disease.

Activities of Daily Living↗

PubMed1997

[Difference between the clinical significance of Credé voiding and Valsalva voiding in the urological management of spina bifida patients].

Retrospective analyses were performed to elucidate the clinical significance between Credé voiding (n = 56) and Valsalva voiding (n = 22) in the urological management of spina bifida patients who do not match the indication of clean intermittent catheterization. The age at initiating the urological management ranged from 0 to 31 years old (mean 2.1) in the Credé voiding and from 0 to 20 years old (mean 4.5) in the Valsalva voiding group. Seventeen patients in the Credé voiding group and 13 in the Valsalva voiding group were followed up for more than 10 years with a mean follow-up period of 14.6 and 13.7 years, respectively. Three patients in the Credé voiding group and one in the Valsalva voiding group showed progression of bladder deformity. In one patient in the latter group, vesicoureteral reflux newly appeared. In the Valsalva voiding group, disappearance or improvement of hydronephrosis was seen in three patients and that of hydroureter in three, bladder deformity in one, and vesicoureteral reflux in one. On the contrary, no patients in the Credé voiding group showed favorable changes in these pathological conditions except for disappearance of vesicoureteral reflux in one patient. Although these findings suggest possible superiority of Valsalva voiding over Credé voiding in the preservation of urinary tract, the differences between the two groups were not statistically significant. The clinical significance of Valsalva voiding remains to be elucidated through further study in neurogenic bladder patients.

Abdomen↗

PubMed1996

Sequential changes in cerebrovascular reserve capacity in three-vessel occlusion rats.

To understand the pathophysiology of hemodynamic compromise, we evaluated the cerebrovascular reserve capacity of a cerebral hemisphere in rats with 3-vessel occlusion (3VO). The bilateral vertebral and left common carotid arteries were occluded in Wistar rats. Sequential changes in local cerebral blood flow (LCBF) and local cerebral plasma volume (LCPV) were measured by [14C]iodoantipyrine and [14C]dextran autoradiography, respectively. There was no significant difference in LCBF between 3VO and control rats at rest. After acetazolamide administration, however, an increase of LCBF in the left hemisphere was less significant compared to that in the right side in the 3VO rats. The left and right ratio was 0.67 +/- 0.15 (P < 0.05) in the parietal cortex and 0.70 +/- 0.10 (P < 0.01) in the caudate nucleus. This asymmetrical response to acetazolamide administration gradually corrected by 7 days after 3VO. A significant increase of the LCPV in the ischemic side was observed between day 0 and the 5th day. The 3VO rat is a useful model for studies on the pathophysiology of a hemodynamically compromised state.

Animals↗

PubMed1996

Interaction of GroEL with conformational states of horse cytochrome c.

GroEL interacts with proteins in denatured states and promotes their efficient folding. To understand the conformational features required for the substrate, we studied the interactions of GroEL with various derivatives of horse cytochrome c including porphyrin-cytochrome c, apo-cytochrome c, and the three fragments containing the heme group, i.e. fragments 1-65, 1-38 and 11-21. Size-exclusion chromatography was performed, taking advantage of the heme absorption of the fluorescence label. Under low-salt conditions, significant binding to GroEL was observed for porphyrin-cytochrome c, apo-cytochrome c, and fragments 1-65 and 1-38, but not for intact cytochrome c or fragment 11-21. On the other hand, under conditions of high ionic strength, only apo-cytochrome c remained tightly bound. Whereas porphyrin-cytochrome c assumes a molten-globule-like compact conformation with a native-like far-UV CD, apo-cytochrome c shows a compact conformation without an ordered secondary structure. The far-UV CD spectra of the three fragments indicated that the fragments lack an ordered secondary structure. These results suggest that the fluctuating and exposed hydrophobic clusters of the substrates are responsible for the interaction, and that the interaction is modulated by electrostatic interaction. It is notable that these characteristics are similar to those of the interaction of cytochrome c derivatives with negatively charged phospholipid membranes, suggesting a common mechanism. Using fluorescence-labeled apo-cytochrome c, we also measured the kinetics of the interaction and estimated the association rate constant to be 5 x 10(7) M-1s-1. This relatively fast association rate constant indicates that the refolding rate of substrate protein is another important factor determining the interaction.

Adenosine Triphosphate↗

PubMed1996

A gamma Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I.

A new type of gamma Gly-268 (GGA) to Glu (GAA) substitution has been identified in a homozygous dysfibrinogen by analyses of the affected polypeptide and its encoding gene derived from a 58 year-old man manifesting no major bleeding or thrombosis. The functional abnormality was characterized by impaired fibrin assembly most likely due to failure to construct properly aligned double-stranded fibrin protofibrils. This presumption was deduced from the following findings: (1) Factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains progressed in a normal fashion, indicating that the contact between the central E domain of one fibrin monomer and the D domain of another took place normally; (2) Nevertheless, factor XIIIa-catalyzed cross-linking of the fibrinogen gamma-chains was obviously delayed, suggesting that longitudinal association of D domains of different fibrin monomers, ie, D:D association was perturbed; (3) Plasminogen activation catalyzed by tissue-type plasminogen activator was not as efficiently facilitated by polymerizing fibrin monomer derived from the patient as by the normal counterpart. Therefore, gamma Gly-268 would not be involved in the 'a' site residing in the D domain, which functions as a complementary binding site with the thrombin-activated 'A' site in the central E domain, but would be rather involved in the D:D self association sites recently proposed for human fibrinogen. Thus, the gamma Glu-268 substitution newly identified in this homozygous dysfibrinogen seems to impair proper alignment of adjacent D domains of neighboring fibrin molecules in the double-stranded fibrin protofibril, resulting in delayed fibrin gel formation.

Afibrinogenemia↗

PubMed1996

Prostaglandin E2 stimulates osteoclast formation via endogenous IL-1 beta expressed through protein kinase A.

The present study was conducted to determine whether endogenous IL-1 is involved as a potent mediator of PGE2-stimulated osteoclast formation in 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3)-primed calvarial cells from mouse embryos. PGE2 induced IL-1 beta gene expression in the primed calvarial cells. IL-1 beta gene expression was also induced in a dose-dependent manner by forskolin and dibutyryl cAMP. PGE2-induced IL-1 beta gene expression was markedly inhibited by H-89, a potent inhibitor of protein kinase A. On the other hand, osteoclast formation in 1 alpha,25-(OH)2D3-primed calvarial cells was also stimulated by forskolin and dibutyryl cAMP, and their stimulatory effects were dose dependent. H-89 also inhibited PGE2-stimulated osteoclast formation. The presence of the IL-1 beta gene product in the conditioned medium of 1 alpha,25-(OH)2D3-primed calvarial cells treated with PGE2 was proved by the results of an immunoprecipitation assay using anti-mouse IL-1 beta Ab. The addition of anti-mouse IL-1 beta Ab to 1 alpha,25-(OH)2D3 primed calvarial cell cultures markedly inhibited PGE2-stimulated osteoclast formation. The stimulatory effect of conditioned medium of primed calvarial cells treated with PGE2 on osteoclast formation was also inhibited by anti-IL-1 beta Ab pretreatment. Furthermore, we found that endogenous IL-6 is partially involved in PGE2-stimulated osteoclast formation.

24,25-Dihydroxyvitamin D 3↗

PubMed1996

Heat-induced chaperone activity of HSP90.

The 90-kDa stress protein, HSP90, is a major cytosolic protein ubiquitously distributed in all species. Using two substrate proteins, dihydrofolate reductase (DHFR) and firefly luciferase, we demonstrate here that HSP90 newly acquires a chaperone activity when incubated at temperatures higher than 46 degrees C, which is coupled with self-oligomerization of HSP90. While chemically denatured DHFR refolds spontaneously upon dilution from denaturant, oligomerized HSP90 bound DHFR during the process of refolding and prevented it from renaturation. DHFR was released from the complex with HSP90 by incubating with GroEL/ES complexes in an ATP-dependent manner and refolded into the native form. alpha-Casein inhibited the binding of DHFR to HSP90 and also chased DHFR from the complex with HSP90. These results suggest that HSP90 binds substrates to maintain them in a folding-competent structure. Furthermore, we found that HSP90 prevents luciferase from irreversible thermal denaturation and enables it to refold when postincubated with reticulocyte lysates. This heat-induced chaperone activity of HSP90 associated with its oligomerization may have a pivotal role in protection of cells from thermal damages.

Animals↗

PubMed1996

An MRI analysis of brain-stem and cerebellar lesions and olivary hypertrophy.

We describe the relations between primary brain stem or cerebellar infarct or haemorrhage and secondary inferior olivary pseudo-hypertrophy (OPH). We identified 17 patients (43.6%) among 39 with brain stem or cerebellar vascular disease who had MRI follow-up more than 3 months after their ictus, with OPH. The primary lesions in the 22 cases without OPH were 11 haemorrhages, including 8 medial cerebellar and 3 brain stem lesions, and 11 infarcts: 4 brain stem lesions without accompanying cerebellar involvement, 2 cerebellar infarcts with brain stem extension, and 5 cerebellar lesions without a brain stem infarct. The causative lesion in the 17 patients with OPH included 5 brain stem and 7 cerebellar haemorrhages and 5 brain stem infarcts; no cerebellar infarcts without brain stem involvement were found to cause OPH. Primary involvement of the tegmentum of the brain stem was closely related to secondary OPH, but we could not characterise MRI differences in the cerebellar lesions between the patients with or without OPH.

Adult↗

PubMed1996

Expression of plasminogen activator inhibitor 2 in the adult and embryonic mouse tissues.

We have studied the expression of plasminogen activator inhibitor 2 (PAI-2) in the adult mouse and during embryonic development using immunohistochemistry and the polymerase-chain reaction. Mouse PAI-2 mRNA was mainly expressed in the skin, bone-marrow, spleen, lung, thymus, and urinary bladder. Immunohistochemical studies suggested that PAI-2 was synthesized in macrophages and epithelial cells such as skin epithelial cells, transitional cells of the urinary bladder, and mesothelial cell of peritoneum and pleura. PAI-2 mRNA and antigen expression was observed only in the skin of 15 day-old mouse embryos. These data suggest that PAI-2 may play a role in protecting the mouse embryo from the protease attack in the amniotic fluid and also in maintaining and/or protecting the structure of various surfaces in the mouse.

Aging↗

PubMed1996

[Molecular approach to detection of micrometastatic prostatic cancer cells in the lymph nodes and the bone marrow].

We detected micrometastatic prostate cancer cells in lymph nodes and bone marrow using reverse transcriptase-polymerase chain reaction (RT-PCT) specific for prostate-specific antigen (PSA). RT-PCR revealed PSA mRNA in two lymph nodes obtained from two patients with negative histological and immunohistochemical analyses for lymph node metastases. Of 26 patients with negative bone scan imaging, 7 had PSA mRNA detected in the bone marrow by RT-PCR. The RT-PCR will be a relevant tool to allow a more accurate clinical assessment of lymph node and bone metastases in patients with prostate cancer.

Bone Marrow Neoplasms↗