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T Ueda

Publications and source records attributed to T Ueda.

At least 1,099 records · Page 61Linked to original sources
PubMed1989

Ontogeny of glutamate accumulating activity in rat brain synaptic vesicles.

The relationship between the ontogeny of the vesicular glutamate uptake system and synaptogenesis in rats was investigated. For this purpose we have developed a simplified procedure for the preparation of crude synaptic vesicles which are sufficiently pure to demonstrate a highly ATP-dependent glutamate uptake. ATP-dependent glutamate uptake into synaptic vesicles was found to increase dramatically starting on postnatal day 10 and reaching a maximum on day 30 (76 +/- 40 and 657 +/- 40 pmol/mg protein/10 min, respectively), correlating well with the active period of synaptogenesis. Stimulation of uptake by chloride also developed in parallel with the vesicular glutamate uptake. In contrast, combined non-ATP-dependent uptake and non-specific binding remained constant (21 +/- 6 pmol/mg protein/10 min). This development of vesicular glutamate uptake during the period of synaptogenesis supports the notion that synaptic vesicles play an important role in glutamate synaptic transmission.

Aging↗
PubMed1989

Mechanism-based isocoumarin inhibitors for serine proteases: use of active site structure and substrate specificity in inhibitor design.

Isocoumarins are potent mechanism-based heterocyclic irreversible inhibitors for a variety of serine proteases. Most serine proteases are inhibited by the general serine protease inhibitor 3,4-dichloroisocoumarin, whereas isocoumarins containing hydrophobic 7-acylamino groups are potent inhibitors for human leukocyte elastase and those containing 7-alkylureidogroups are inhibitors for procine pancreatic elastase. Isocoumarins containing basic side chains that resemble arginine are potent inhibitors for trypsin-like enzymes. A number of 3-alkoxy-4-chloro-7-guanidinoisocoumarins are potent inhibitors of bovine thrombin, human factor Xa, human factor XIa, human factor XIIa, human plasma kallikrein, porcine pancreatic kallikrein, and bovine trypsin. Another cathionic derivative, 4-chloro-3-(2-isothiureidoethoxy) isocoumarin, is less reactive toward many of these enzymes but is an extremely potent inhibitor of human plasma kallikrein. Several guanidinoisocoumarins have been tested as anticoagulants in human plasma and are effective at prolonging the prothrombin time. The mechanism of inhibition by this class of heterocyclic inactivators involves formation of an acyl enzyme by reaction of the active site serine with the isocoumarin carbonyl group. Isocoumarins with 7-amino or 7-guanidino groups will then decompose further to quinone imine methide intermediates, which react further with an active site residue (probably His-57) to form stable inhibited enzyme derivatives. Isocoumarins should be useful in further investigations of the physiological function of serine proteases and may have future therapeutic utility for the treatment of emphysema and coagulation disorders.

Binding Sites↗
PubMed1989

Clinical pharmacology of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine in patients with hematologic malignancies.

The pharmacokinetics of oral N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC), a lipophilic and deaminase-resistant derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), were determined in patients with hematologic malignancies. The concentration of ara-C and 1-beta-D-arabinofuranosyluracil (ara-U), metabolites of PLAC, were measured by radioimmunoassay and gas chromatography-mass spectrometry-mass fragmentography, respectively. The concentration of PLAC was determined by measuring ara-C, which was derived from PLAC by hydrolyzation. In six patients given an oral bolus of PLAC (300 mg/m2), the plasma-disappearance curve of PLAC corresponded to a one-compartment open model, including first-order absorption. The peak plasma level was 22.9 +/- 6.4 ng/ml, and the predicted time to reach the peak level was 2.5 +/- 1.0 h. The elimination half-life was 3.8 +/- 2.7 h. The plasma ara-C level increased slowly to 6.9 ng/ml during the 1st 2-3 h after administration and remained over 1.0 ng/ml for 12 h. Plasma ara-U was detectable for at least 24 h, with a peak concentration of 376 ng/ml at 6 h. Urinary PLAC excretion was below the limit of detection (5 ng/ml) in all cases. Prolonged urinary ara-C and ara-U excretion was detected, but the total recovery rate was low (6.7% in 24 h) and varied between patients. In spite of the lipophilic nature of the drug, the PLAC concentration in the cerebrospinal fluid, measured at 3 or 6 h, was below the limit of detection in all four patients with no meningeal involvement. This study showed low but persistent levels of PLAC in plasma and tissues, with a continuous release of small amounts of ara-C, which demonstrated antitumor activity in patients with hematologic malignancies.

Adult↗
PubMed1989

Phase II trial of carboplatin in patients with advanced germ-cell testicular tumors and transitional cell carcinomas of the urinary tract.

Carboplatin, an analog of cisplatin, was evaluated in a phase II study involving 25 patients with advanced testicular tumor and 45 with transitional cell carcinoma (TCC) of the urinary tract; 21 and 38 cases, respectively, were evaluable for response. Prior treatment with cisplatin-based chemotherapy had occurred in 7 of the testicular cancer patients and in 11 with TCC. The response rate (complete + partial response) in testicular tumors was 47.6%. The best response rate was observed in seminomas (70.0%), whereas the response rate in nonseminomas was 27.3%. The seminoma patients had mainly stage IIIA or less than IIIA disease, with metastatic lesions restricted to the lymph nodes. Three responses were seen in patients previously treated with cisplatin. In TCC, the response rate was 18.4%. Good-risk patients were treated with a dose of 400 mg/m2 every 4 weeks, whereas poor-risk patients received a lower dose of 300 mg/m2. The response rates for good-risk patients were 50.0% in testicular lesions and 26.1% in TCC. For poor-risk patients, the response rates were 40.0% and 6.7%, respectively. Carboplatin was well tolerated, with no significant renal impairment or ototoxicity detected. Nausea and vomiting were experienced by 51.7% of patients, but the severity was low; half of these patients demonstrated WHO grade I toxicity. However, myelosuppression was severe. In conclusion, carboplatin demonstrated activity in both testicular tumors and TCC and is worthy of further study, especially in combination with other active drugs.

Adult↗
PubMed1989

Cooperative effects of gamma-interferon and 1 alpha, 25-dihydroxyvitamin D3 on in vitro differentiation of the blast cells of RAEB and RAEB-T.

We added recombinant human gamma-interferon (gamma-IFN) and 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25 (OH)2D3) to the bone marrow cells from six patients with RAEB or RAEB-T in liquid suspension cultures. After cultivation for 7 to 9 days, numerical, morphological and functional changes of the cells were assessed. gamma-IFN and 1 alpha, 25 (OH)2D3 additively suppressed cell growth, especially the number of blast cells decreased. The expression of alpha-naphthylbutyrate esterase (NBE) activity appeared to be promoted but that of naphthol AS-D chloroacetate esterase (NAE) activity was apparently suppressed by the addition of gamma-IFN and/or 1 alpha, 25 (OH)2D3. The percentage of NBT reduction-positive cells and latex-phagocytizing cells was only slightly increased by both agents. These results indicate that gamma-IFN and 1 alpha, 25 (OH)2D3 cooperate to induce monocytoid differentiation of the patients' blast cells. Combination therapy with both agents merits further study.

Adult↗
PubMed1989

Urinary metabolite levels in workers handling p-tert-butylphenol as an index of personal exposure.

Occupational exposure to p-tert-butylphenol (PTBP) was studied in a workplace where workers were engaged in packing this alkylphenol in bags or transporting the bags by fork-lift. The geometrical mean of eight-hour-time-weighted-average (8 h-TWA) value for personal ambient PTBP level of the packers was 0.39 mg/m3 (n = 15), higher than that of the carriers (0.10 mg/m3, n = 5). Amounts of PTBP collected in the respirators used by the workers were in proportion to the 8 h-TWA values but lower than the estimated theoretical amounts; considerable amounts of PTBP were assumed to be absorbed through the respiratory tract. The urine excreted during the latter half of the shift showed the highest levels of PTBP (geometrical mean: packer, 5.07 micrograms/ml, n = 20; carrier, 3.03 micrograms/ml, n = 8). When the workers were away from the workplace, PTBP levels decreased; most was excreted within 24 h. Correlation between the urinary PTBP levels and 8 h-TWA values was significant (r = 0.46, n = 19, P less than 0.05), but its extent was weak. The total amounts of urinary PTBP excreted for 24 h after the start of the shift were two to three times higher than the estimated respiratory absorption of PTBP; PTBP was assumed to be absorbed not only through the respiratory tract but also through intact skin. It was concluded that the personal ambient PTBP level is not a suitable index for personal exposure, and biological monitoring via the PTBP level in the urine excreted at the end of the each shift is useful for the evaluation of personal exposure.

Air Pollutants, Occupational↗
PubMed1989

Induction of DNA double-strand breaks in Chinese hamster V79 cells by 2-chlorodeoxyadenosine.

2-Chlorodeoxyadenosine was found to induce DNA double-strand breaks as well as cell death in log-phase Chinese hamster V79 cells. The induction of DNA double-strand breaks, measured by a neutral elution technique, was observed after a 2-h incubation of the cells in the presence of 5 microM of 2-chlorodeoxyadenosine, but these breaks were almost rejoined by a subsequent 1-h incubation, even though this drug was present in the medium during incubation. This repair was prevented by the addition of nicotinamide, which is known to inhibit poly(ADP-ribose) synthesis that is strongly associated with the DNA ligation, but not prevented by the addition of 9-beta-D-arabinofuranosyladenine (araA), which is known to inhibit DNA polymerization. These results suggest that the repair of CdA-induced double-strand breaks is achieved by ligation alone without DNA polymerization. When 35 microM of cycloheximide and 1.3 mM of dibutyryl cAMP were added to the medium, it was found that the induction of double-strand breaks by 2-chlorodeoxyadenosine was suppressed, while the cytotoxicity of 2-chlorodeoxyadenosine measured by colony-forming ability was not interfered with. These results suggest that the induction of DNA double-strand breaks is not associated with the cytotoxicity of this drug.

2-Chloroadenosine↗
PubMed1989

Localization and subcellular distribution of cellular ras gene products in rat brain.

Localization and subcellular distribution of the cellular ras gene products (c-ras p21s) in rat brain were studied by immunofluorescence and immunoblotting using a monoclonal antibody recognizing all of Ki-, Ha- and N-ras p21s. In immunohistochemical analysis, strong immunoreactivity for ras p21s was observed in the neuropile of cerebral and cerebellar cortex. On the other hand, the immunoreactivity of the neuronal perikarya and that of white matter were weak and that of non-neuronal cells was undetectable. In subcellular fractionation analysis of cerebrum, c-ras p21s were found mostly in the particulate fractions and almost half of the particulate-bound c-ras p21s were recovered in the P2 fraction containing myelin, synaptosomes and mitochondria, approximately one-third were in the P3 fraction containing microsomes, and the rest were in the P1 fraction containing nuclei and cell debris. In further fractionation of the P2 fraction, most of c-ras p21s were associated with synaptosomal fraction. In the synaptosomal fraction, c-ras p21s were highly concentrated in the fractions rich in synaptic plasma membranes and were poorly present in the other fractions rich in synaptic vesicles, intrasynaptosomal mitochondria or postsynaptic densities. The content of c-ras p21s of the original homogenate was calculated to be 0.05% of the total protein and c-ras p21s were distributed in the fractions rich in synaptic plasma membranes with approximately 4-fold enrichment over the original homogenate. These results indicate that c-ras p21s are mainly localized in the synaptic plasma membranes and microsomes and suggest that they may participate in some specific neuronal functions at these sites.

Animals↗
PubMed1989

Malignant lymphoma of the testis: histological and immunohistological study of 28 cases.

Histological and immunohistological studies were made in 28 patients with testicular lymphoma who presented with a right (15), left (11) or bilateral (2) scrotal swelling. Patient age at hospitalization ranged from 39 to 87 years, with a median age of 64 years. The disease was stage 1 in 12 patients, stage 2 in 11 and stage 3 in 5. Histologically, most of the neoplasms were of the diffuse large cell type, with an immunoblastic type being the most common. Immunohistochemistry revealed that all but 2 cases were of the B cell type. None of the tumors reacted with monoclonal antibody for T cell. These findings suggested that testicular lymphoma exclusively consisted of the B cell type, identical to previous reports of extranodal lymphomas other than those in the skin. The pertinent literature is reviewed and the histogenesis of testicular lymphoma is discussed.

Adult↗
PubMed1989

Active transport of gamma-aminobutyric acid and glycine into synaptic vesicles.

Although gamma-aminobutyric acid (GABA) and glycine are recognized as major amino acid inhibitory neurotransmitters in the central nervous system, their storage is poorly understood. In this study we have characterized vesicular GABA and glycine uptakes in the cerebrum and spinal cord, respectively. We present evidence that GABA and glycine are each taken up into isolated synaptic vesicles in an ATP-dependent manner and that the uptake is driven by an electrochemical proton gradient. Uptake for both amino acids exhibited kinetics with low affinity (Km in the millimolar range) similar to vesicular glutamate uptake. The ATP-dependent GABA uptake was not inhibited by the putative amino acid neurotransmitters glycine, taurine, glutamate, or aspartate or by GABA analogs, agonists, and antagonists. Similarly, ATP-dependent glycine uptake was hardly affected by GABA, taurine, glutamate, or aspartate or by glycine analogs or antagonists. The GABA uptake was not affected by chloride, which is in contrast to the uptake of the excitatory neurotransmitter glutamate, whereas the glycine uptake was slightly stimulated by low concentrations of chloride. Tissue distribution studies indicate that the vesicular uptake systems for GABA, glycine, and glutamate are distributed in different proportions in the cerebrum and spinal cord. These results suggest that the vesicular uptake systems for GABA, glycine, and glutamate are distinct from each other.

Adenosine Triphosphatases↗
PubMed1989

Level of expression of the tomato rbcS-3A gene is modulated by a far upstream promoter element in a developmentally regulated manner.

By Agrobacterium-mediated transformation we have demonstrated that a 1.10-kilobase promoter sequence from the tomato rbcS-3A gene confers light-inducible and organ-specific expression upon fusion to the bacterial chloramphenicol acetyltransferase gene. A biphasic expression profile was obtained by 5' deletion analysis of this promoter, indicating the presence of both positive and negative regulatory elements. A severe reduction in the level of expression was observed when the 5'-terminal 90 base pairs were deleted from the 1.10-kilobase promoter. DNA sequence elements responsible for light inducibility and organ specificity of the gene reside within the -374 base pairs of the proximal part of the promoter and the sequences spanning from -374 to -205 are essential for promoter function. The DNA sequences upstream from -374 modulate the level of expression in leaf tissue; this modulation is under developmental control.

Base Sequence↗
PubMed1989

Glutamate uptake into synaptic vesicles: competitive inhibition by bromocriptine.

The ATP-dependent uptake of L-glutamate into synaptic vesicles has been well characterized, implicating a key role for synaptic vesicles in glutamatergic neurotransmission. In the present study, we provide evidence that vesicular glutamate uptake is selectively inhibited by the peptide-containing halogenated ergot bromocriptine. It is the most potent inhibitor of the agents tested: the IC50 was determined to be 22 microM. The uptake was also inhibited by other ergopeptines such as ergotamine and ergocristine, but with less potency. Ergots devoid of the peptide moiety, however, such as ergonovine, lergotrile, and methysergide, had little or no effect. Although bromocriptine is known to elicit dopaminergic and serotonergic effects, its inhibitory effect on vesicular glutamate uptake was not mimicked by agents known to interact with dopamine and serotonin receptors. Kinetic data suggest that bromocriptine competes with glutamate for the glutamate binding site on the glutamate translocator. It is proposed that this inhibitor could be useful as a prototype probe in identifying and characterizing the vesicular glutamate translocator, as well as in developing a more specific inhibitor of the transport system.

Adenosine Triphosphate↗
PubMed1989

Effects of recombinant G-CSF and GM-CSF on in vitro differentiation of the blast cells of RAEB and RAEB-T.

To evaluate the effects of recombinant G-CSF and GM-CSF on RAEB and RAEB-T cells, blast cells from 6 patients were incubated in liquid culture systems with these CSFs for 7 days, and their numerical, morphological and functional changes were assessed. Both CSFs stimulated cell growth, but decreased the proportion of blast cells in 5 of the 6 cases. Karyotypic abnormalities persisted during cultivation in some cases. The CSFs also stimulated the expression of part of the esterase activities, and a positive interaction of both CSFs was seen in part. Although CSFs had no significant effects on the ability of cells to reduce NBT or to phagocytize latex particles, the results indicated that they induce partial differentiation of blast cells. It appears that such pathological cells still retain the capacity to respond to growth factors.

Adult↗
PubMed1989

Tolerance of the cerebral venous system to retrograde perfusion pressure in focal cerebral ischemia in rats.

Using quantitative double-tracer autoradiography, we examined the tolerance of the rat cerebral venous system in focal cerebral ischemia to retrograde perfusion pressure into the inferior cerebral vein. At perfusion pressures of less than 150 mm Hg, there was no significant change in local cerebral blood flow (LCBF) and blood-brain barrier (BBB) permeability. At pressures of greater than 170 mm Hg, significant changes occurred in BBB permeability in the superficial cortical layers and there was a mild reduction of LCBF. In the group of rats subjected to 200 mm Hg perfusion pressure, the change in BBB permeability extended to the entire cortical zone and significant reduction of LCBF occurred. Our results indicate for the first time that during conditions of focal cerebral ischemia, the rat cerebral venous system can tolerate up to 150 mm Hg of retrograde perfusion pressure into the cerebral venous system without any change in BBB permeability or in LCBF. However, progressive change in BBB permeability and reduction in LCBF occur once the perfusion pressure exceeds 170 mm Hg. This finding may permit more efficient delivery of cytoprotective agents into ischemic tissue.

Animals↗
PubMed1989

Transvenous perfusion of the brain with verapamil during focal cerebral ischemia in rats.

We report on the effect of calcium channel blocker verapamil administered into the inferior cerebral vein in rats 1 hour after occlusion of the middle cerebral artery. Twenty-four rats were divided into four groups of six rats each. Group A rats received no medication. The other three groups received 0.1 mg verapamil/kg/2 hr. Group B rats received verapamil intravenously. Group C and D rats received verapamil and autologous arterial blood by transvenous perfusion of the brain, Group C rats at 100 mm Hg perfusion pressure and Group D rats at 150 mm Hg perfusion pressure. The administration of verapamil started 1 hour after middle cerebral artery occlusion and lasted for 2 hours. Three hours after occlusion, we used double- or single-tracer autoradiography with 4-[18F]fluoroantipyrine or [14C]iodoantipyrine and [14C]alpha-aminoisobutyric acid as tracers to study the brains for local cerebral blood flow and blood-brain barrier permeability changes. Group C showed a significant increase of local cerebral blood flow in the parietal cortex (89%, p less than 0.01) and sensorimotor cortex (64%, p less than 0.05) compared with Group A. Group D showed an extensive and striking increase in local cerebral blood flow of the ischemic cortical and subcortical areas (57-100%, p less than 0.05). Group B showed no significant changes but exhibited further reduction of local cerebral blood flow in the ischemic cerebral hemisphere associated with slightly increased local cerebral blood flow in the nonischemic cerebral hemisphere compared with Group A. There was no change of blood-brain barrier permeability in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗