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Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 163 records · Page 9Linked to original sources
PubMed1994

Inhibition of tubular morphogenesis in human microvascular endothelial cells by co-culture with chondrocytes and involvement of transforming growth factor beta: a model for avascularity in human cartilage.

Tube formation in collagen gel was induced in human omental microvascular endothelial (HOME) cells in the presence of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). TGF-alpha enhanced the expression of the tissue type plasminogen activator (t-PA) gene, whereas TGF-beta increased the expression of the PA inhibitor-1 (PAI-1) gene and inhibited that of the t-PA gene. TGF-beta inhibited the tube formation of HOME cells in type I collagen gel that was enhanced in response to TGF-alpha. We have recently established an angiogenesis model in vitro in which vascular endothelial cells on type I collagen gel in an inner chamber are co-cultured with other types of cells in an outer chamber. Here we examined whether the EGF/TGF-alpha-induced tube formation in HOME cells was modulated by human chondrocytes co-culture in the outer chamber. TGF-alpha-dependent tube formation of HOME cells was inhibited when human chondrocytes were co-cultured in the outer chamber. This chondrocyte-induced inhibition of tube formation was partly abrogated by co-administration of anti-TGF-beta antibody. These findings suggest that TGF-beta is partly involved in the human chondrocyte-dependent inhibition of tube formation by human microvascular endothelial cells. This is the first model system demonstrating that avascularity of human chondrocytes is partly due to TGF-beta family produced from them.

Cartilage↗
PubMed1994

[MR imaging findings of nonketotic hyperglycinemia. 2 cases of neonatal onset].

We presented MR (magnetic resonance) images findings of the brain in nonketotic hyperglycinemia (NKH) from 2 patients of neonatal onset. MR findings in our cases of NKH are compatible with the pathological alterations described in the literature; MR images revealed delayed myelination of the cerebral white matter and hypoplasia of the corps callosum. The latter finding particularly seemed to be relatively characteristic to NKH. MR examination is the imaging modality of choice for this disease because it can demonstrate the degree of myelination, and development of the corpus callosum particularly on sagittal section.

Brain↗
PubMed1994

Functional and morphological abnormalities of mitochondria in human cells containing mitochondrial DNA with pathogenic point mutations in tRNA genes.

mtDNA with a point mutation in the tRNA(Ile) gene at nucleotide position 4269 found in a patient with fatal cardiomyopathy and mtDNA with a point mutation in the tRNA(Arg) gene at 10410 found in a patient with Alpers disease were transferred cytoplasmically to rho zero HeLa cells (HeLa cells lacking mtDNA) to determine whether these novel mtDNA mutations in the tRNA genes are responsible for the defects in mitochondrial respiration function observed in these diseases. Cybrid clones (clones of rho zero HeLa cells with mtDNA from the patients) were isolated, and respiratory function and morphology of the mitochondria of the cybrid clones containing wild-type mtDNA and mutant mtDNA predominantly were compared. The results showed that accumulation of mutant mtDNA at 4269 alone without defects in the nuclear genome was sufficient to produce a disease phenotype, while mutant mtDNA at 10410 was not related to pathogenesis and reflected one of the rare polymorphic sites of human mtDNA. Moreover, we found that mitochondria in living cells were significantly swollen only when they contained predominantly the pathogenic mutant mtDNA, suggesting that the functional abnormality of mitochondria induced by pathogenic mtDNA mutations in tRNA genes is always associated with their swollen structure.

Cardiomyopathies↗
PubMed1994

Expression of the mouse interleukin-2 receptor gamma chain in various cell populations of the thymus and spleen.

Expression of the gamma chain, which is shared among functional receptor complexes for interleukin (IL)-2, IL-4 and IL-7, was examined with hematopoietic cells in mouse thymus and spleen by flow cytometry. The gamma chain was expressed in cell populations from the spleen. Stimulation with concanavalin A and lipopolysaccharide caused fluctuation in expression of the gamma chain in T and B cells, respectively. T lineage cells developing in the adult thymus expressed the gamma chain. Fetal thymus at day 15 contained mostly immature thymocytes, which also expressed the gamma chain. These results demonstrate that the gamma chains is widely expressed in T lineage cells, probably indicating that the gamma chain plays a role not only in the proliferation of mature hematopoietic cells but also in the development of immature cells through signal transduction as a common receptor subunit for multiple cytokines.

Animals↗
PubMed1994

Effects of several 5-HT1A agonists on hippocampal rhythmical slow activity in unanesthetized rats.

We examined the effect of 5-hydroxytryptamine (5-HT)1A agonists on walking related, atropine-resistant, rhythmical slow activity (wr-RSA) of the hippocampus in rats. Selective 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), flesinoxan, buspirone and ipsapirone significantly decreased the power value of 7-9 Hz band activity and the median frequency of wr-RSA. The order of potency was 8-OH-DPAT > flesinoxan = buspirone in power reduction. The 5-HT1A antagonists, (-)pindolol, (-)propranolol and spiperone, inhibited the effect of 8-OH-DPAT on wr-RSA. Pretreatment with parachlorophenylalanine did not abolish the effect of 8-OH-DPAT. These results indicate that 5-HT1A agonists reduce both power and median frequency values of wr-RSA through activation of post-synaptic 5-HT1A receptors in the forebrain in unanesthetized rats, in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Expression of the IL-2 receptor gamma chain on various populations in human peripheral blood.

We have established two rat mAbs, TUGh4 and TUGh5, specific for the human gamma chain of the IL-2 receptor (IL-2R), which is known to be shared among receptors for IL-2, IL-4 and IL-7. The antibodies bound to cell lines transfected with the human gamma chain gene but not to their parental cell lines, and precipitated 65-70 and 80-90 kDa cell surface molecules from lysates of human T cells surface-labeled with Na125I and chemically cross-linked with [125I]IL-2 respectively. Flow cytometry with TUGh4 and TUGh5 detected the gamma chain in a wide variety of peripheral blood cell populations including CD4+ T cells, CD8+ T cells, CD20+ B cells, CD56+ natural killer cells, CD14+ monocytes and granulocytes, contrasting with expression of the alpha and beta chains of IL-2R.

Antibodies, Monoclonal↗
PubMed1994

Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells.

Epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration, chemotaxis, and the expression of tissue-type plasminogen activator (t-PA) in human omental microvascular endothelial (HOME) cells. Hepatocyte growth factor (HGF) stimulated cell proliferation, but had a negligible stimulatory effect on cell migration, the expression of t-PA and tube-like formation into collagen gel in HOME cells. Basic fibroblast growth factor stimulated cell proliferation, cell migration, tubulogenesis and the expression of urokinase-type plasminogen activator (u-PA) in bovine aortic endothelial (BAE) cells. HOME and BAE cells had both high- and low-affinity receptors for HGF. In BAE cells, u-PA activity and tube-like structures in collagen gel were induced in the presence of HGF alone. In contrast, in HOME cells, t-PA activity and tube-like structures were induced in the presence of TGF-alpha alone, but not in the presence of HGF alone. However, we observed a marked induction of tube formation by HOME cells when both t-PA and HGF were added simultaneously. In the model system for tumor angiogenesis, when HOME cells were co-cultured with a renal cancer cell line, KPK13, tube-like structures were induced in the presence of HGF:KPK13 cells expressed large amounts of t-PA mRNA. Our present study suggested that HGF in concert with active t-PA could be angiogenic in HOME cells.

Cell Line↗
PubMed1994

[Detection of Mycoplasma genitalium from male patients with non-gonococcal urethritis by polymerase chain reaction].

Mycoplasma genitalium causes urethritis in non-human primates, but studies on its pathogenicity in man have been hampered by the difficulty in isolating this oragnism in culture. We have used a specific polymerase chain reaction to examine the role of M. genitalium in non-gonococcal urethritis (NGU). Oligonucleotide primers were used to amplify a 281 bp of 140-KDa adhesin gene of M. genitalium. A characteristic PCR product was amplified, when M. genitalium DNA was template for the PCR. No amplified product was detected in Mycoplasma pneumoniae DNA, Mycoplasma hominis DNA or other bacterial DNAs. M. genitalium DNA was detected in urethral swabs from 17 (14.9%) of 114 men with NGU. Three (9.1%) of the 33 men with Chlamydia-positive NGU and 14 (17.3%) of the 81 with Chlamydia-negative NGU were positive for M. genitalium DNA, but 29 men without urethritis were negative. The prevalence of M. genitalium in NGU and in Chlamydia-negative NGU was significantly higher than that in the normal control. These findings suggest that M. genitalium would be a cause of NGU.

Chlamydia Infections↗
PubMed1994

Effects of zopiclone, triazolam, and nitrazepam on standing steadiness.

We examined the effects of the nonbenzodiazepine hypnotic zopiclone and the benzodiazepine hypnotics triazolam and nitrazepam on standing steadiness. Eight healthy volunteers received placebo, zopiclone (7.5 mg), triazolam (0.25 mg), and nitrazepam (5 mg) in a random-order, double-blind crossover design. Postural sway was assessed before and 1 and 2 h after drug administration using a stabilometer connected to a microcomputer. Triazolam significantly impaired standing steadiness. Zopiclone also impaired standing steadiness but the degree of impairment seemed to be less marked. Nitrazepam 5 mg had no significant effects on postural sway. Triazolam 0.25 mg, zopiclone 7.5 mg, and nitrazepam 5 mg, which are reported to be equipotent to each other as hypnotics, are not equipotent with respect to their effects on postural sway.

Adult↗
PubMed1994

Human cytomegalovirus neutralizing antibody response in Japanese children with bone marrow transplantation.

Thirty-two children with bone marrow transplantation (BMT) received intravenous injections of gammaglobulin (IVIG) with a high titer of neutralizing (NT) antibody against human cytomegalovirus (HCMV) (200 mg/kg/week) from 1 week before to 4 months after transplantation. NT antibody titers before BMT and the highest levels in serial determinations conducted after BMT were compared for each patient. They were classified into three groups according to the antibody response: primary HCMV infection as group I, endogenous reactivation or external reinfection as group II, and indeterminable cases as group III. Two (6.3%) out of 32 patients examined had BMT-associated primary HCMV infections, but did not show any clinical symptoms. Significant changes in clinical parameters were also lacking in all the other 30 patients, independent of whether they shed viruses into the urine, or demonstrated on antibody boost. It was concluded from the group variation that the antibody response was indeed due to the engraftment of BMT, rather than to a direct effect of treatment with IVIG. Our results further indicate that passive immunization with HCMV antibody does not prevent infection, but confers some protection against symptomatic disease.

Adolescent↗
PubMed1994

Single-unit responses of serotonergic dorsal raphe neurons to 5-HT1A agonist and antagonist drug administration in behaving cats.

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was recorded in free-moving cats in response to i.v. administration of 5-hydroxytryptamine (5-HT)1A agonist and antagonist drugs. The 5-HT1A agonist drugs 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), ipsapirone, buspirone and 5-methoxy-N,N-dimethyltryptamine produced a rapid, dose-dependent inhibition of neuronal activity. 8-OH-DPAT (ED50 = 1.5 micrograms/kg) was approximately 45 times more potent than ipsapirone, buspirone or 5-methoxy-N,N-dimethyltryptamine (ED50 range = 6.0-6.8 micrograms/kg) in producing inhibition, and all drugs were more effective when cats were inactive (e.g., drowsiness) than during periods of behavioral arousal (e.g., active waking). Administration of the 5-HT1A autoreceptor antagonist spiperone (0.25 and 1 mg/kg) produced a rapid, dose-dependent increase in the firing rate, suggesting that under physiological conditions serotonergic neurons are controlled by tonic feedback inhibition. This effect was evident during wakefulness (a period of relatively high neuronal activity), but not during sleep (a period of relatively low neuronal activity). Spiperone also blocked the inhibitory action of 8-OH-DPAT in a dose- and time-dependent manner. There was a strong positive correlation between the magnitude of spiperone-induced neuronal activation and blockade of 8-OH-DPAT-induced neuronal suppression. These effects of spiperone cannot be attributed to its dopaminergic D2 or serotonergic 5-HT2 antagonist properties, because administration of haloperidol and ritanserin produced no increase in neuronal activity and did not block the action of 8-OH-DPAT. These results confirm the marked sensitivity of serotonergic dorsal raphe nucleus neurons to selective 5-HT1A agonist compounds in unanesthetized animals and suggest that 5-HT1A somatodendritic autoreceptors exert a tonic inhibitory influence on the firing rate of these neurons during periods of behavioral activation, but not during periods of behavioral quiescence.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Effects of the putative 5-hydroxytryptamine1A antagonists BMY 7378, NAN 190 and (-)-propranolol on serotonergic dorsal raphe unit activity in behaving cats.

Recent evidence from our laboratory has demonstrated that blockade of somatodendritic 5-hydroxytryptamine (5-HT)1A autoreceptors by systemic administration of spiperone increases the firing rate of central serotonergic neurons in awake cats. The present study examines the effects of three other putative 5-HT1A antagonists (BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4,5]decane-7,9-dione), NAN 190 [1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine) and (-)-propranolol) on the single-unit activity of serotonergic neurons recorded in the dorsal raphe nucleus of free-moving cats. Systemic administration of the phenylpiperazine derivatives BMY 7378 (5-100 micrograms/kg i.v.) and NAN 190 (5-250 micrograms/kg i.v.) produced a rapid, dose-dependent inhibition of neuronal activity with BMY 7378 being approximately twice as potent as NAN 190 (ED50 = 15.3 micrograms/kg vs. 34.2 micrograms/kg). The suppression of neuronal activity produced by both compounds was greatly attenuated by spiperone (1 mg/kg i.v.). Systemic administration of (-)-propranolol (2 and 4 mg/kg i.v.) produced a modest suppression of serotonergic neuronal activity which did not appear to be dose-related. The ability of BMY 7378, NAN 190 and (-)-propranolol to block the suppression of neuronal activity produced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A agonist, was also examined. Pretreatment with these compounds had no significant effect on the inhibitory response of serotonergic neurons to 8-OH-DPAT challenge. These results indicate that BMY 7378 and NAN 190 act as agonists rather than antagonists at the somatodendritic 5-HT1A autoreceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Quantitative evaluation of electron transport system proteins in mitochondrial encephalomyopathy.

The levels of mitochondrial electron transport system proteins cytochrome c oxidase (COX) and complex III were measured in muscle fibers of patients with mitochondrial encephalomyopathy using quantitative immunoelectron microscopy. In a patient with Leigh's encephalopathy, immunoreactive COX protein was decreased to 20% of the normal mean value in all muscle fibers examined, while the amount of complex III was within the normal range. In a patient with fatal infantile COX deficiency, the level of COX protein was found to be decreased to 27-40% of the normal value in all muscle fibers examined. In patients with mitochondrial myopathy, encephalopathy, lactic acidosis associated with stroke-like episodes (MELAS) and chronic progressive external ophthalmoplegia (CPEO), COX protein levels were decreased to 20% of normal in muscle fibers lacking COX activity. In normal fibers, however, COX protein levels were also normal. The amount of complex III protein was normal in COX-deficient muscle fibers. In two patients, in situ hybridization was performed for detection of mitochondrial mRNA. Mitochondrial mRNAs were found to be abundant in muscle fibers with decreased COX protein, suggesting a defect at the mitochondrial protein-synthesis level in a COX-deficient muscle fiber.

Adult↗
PubMed1993

Non-ketotic hyperglycinaemia: molecular lesion, diagnosis and pathophysiology.

Non-ketotic hyperglycinaemia (NKH) is a well-recognized metabolic cause of life-threatening illness in the neonate. The fundamental defect is in the glycine cleavage system, which consists of four protein components. Our study revealed that the majority of NKH patients had a specific defect in P-protein (glycine decarboxylase). The primary lesion of NKH at gene level was investigated, using cDNA encoding human glycine decarboxylase. A three-base deletion resulting in deletion of Phe756 was found in a Japanese patient with NKH. The majority of NKH patients in Finland, where there is a high incidence of NKH, were found to be due to a common mutation, a point mutation resulting in the amino acid substitution of Ile564 for Ser564. Prenatal diagnosis is feasible by determining the activity of the glycine cleavage system and is also possible by DNA analysis. Recent findings suggest that a high concentration of glycine in the brain may contribute to the pathophysiology of NKH by overactivating N-methyl-D-aspartate receptors allosterically, which may result in intracellular calcium accumulation, DNA fragmentation and neuronal death. These provide the possibility that early treatment with N-methyl-D-aspartate receptor antagonist may prevent brain damage in NKH.

Amino Acid Metabolism, Inborn Errors↗