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Biomedical subjects

S Tsuda

Publications and source records attributed to S Tsuda.

At least 163 records · Page 9Linked to original sources
PubMed1992

[Clinical evaluation of ceftazidime monotherapy for infections complicated with hematological disorders].

Fifty patients with infections associated with hematological disorders were treated with ceftazidime (CAZ). Among them 44 cases were evaluable, including 21 with acute leukemia, 17 with malignant lymphoma, and 6 with other hematological disorders. Excellent responses were observed in 15 patients (34.1%) and good responses in 15 (34.1%), with an overall efficacy rate of 68.2%. The efficacy rate among sepsis and suspected sepsis cases was 67.6%. This treatment was also effective in 7 of 10 cases in which neutrophil counts were less than 500/mm3 through the course of administration. Laboratory abnormalities included mild eosinophilia in 1 case, slight elevation of GOT in 1 case and slight elevation of GPT in 1 case. These results suggest that CAZ is an effective and safe antibiotics for the treatment of infections in patients with hematological disorders.

Adult↗
PubMed1991

Effects of Bay K 8644, a Ca2+ channel agonist, on [3H]norepinephrine release in hypothalamus of spontaneously hypertensive rats.

We describe the effects of Bay K 8644, a dihydropyridine-sensitive Ca2+ channel agonist, on [3H]norepinephrine (NE) release from the hypothalamus of spontaneously hypertensive rats (SHR). The electrical stimulation-evoked [3H]NE release was greater in hypothalamic slice of SHR than in those of Wistar Kyoto (WKY) rats. Bay K 8644 (10(-6) M) significantly increased the stimulation-evoked [3H]NE release in SHR. However, the agonist showed no significant effects in normotensive WKY rats. The results suggest that the dihydropyridine-sensitive Ca2+ channels might participate actively in the regulation of the central sympathetic tone of hypertension.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Differences in the mode of lethality produced through intravenous and oral administration of organophosphorus insecticides in rats.

This study was undertaken to investigate the possibility that mechanisms other than cholinesterase (ChE) inhibition account for the acute toxicity of organophosphorus insecticide. Both the P = O type insecticide (direct ChE inhibitors: chlorfenvinphos and dichlorvos) and the P = S type insecticide (indirect ChE inhibitors: diazinon and fenthion) were employed. Rats treated with lethal doses of intravenous and oral P = O type insecticides and oral P = S type insecticides exhibited typical signs of anti-ChE poisoning along with marked inhibition of brain and erythrocyte ChE activity. In contrast, rats given lethal doses of intravenous P = S type insecticides exhibited tonic convulsions and opisthotonos, with only slight inhibition of ChE activities. When P = O type insecticides were intravenously administered to anesthetized and conscious rats, animals exhibited typical anti-ChE poisoning signs in cardiorespiration: hypertension and apnea which were antagonized by atropine. After administration of lethal doses of P = O type insecticides, breathing disappeared before the cessation of heart beats. Rats receiving lethal doses of intravenous P = S type insecticides did not show hypertension, but exhibited transient cessation of breathing and heart beats. Breathing was observed after the disappearance of heart beats. The electroencephalogram (EEG) was characterized by spike and wave complexes. The EEG and cardiorespiratory changes were not antagonized by atropine. It was concluded that lethality following intravenous P = S type insecticides may be independent of ChE inhibition.

Administration, Oral↗
PubMed1991

Chronic toxicity studies with thiram in Wistar rats and beagle dogs.

Groups of 64 male and 64 female Wistar rats were given thiram at constant dietary doses of 0, 3, 30, and 300 ppm (0, 0.1, 1.2, and 11.6 mg/kg/day for males and 0, 0.1, 1.4, and 13.8 mg/kg/day for females) for 104 weeks. Eight males and eight females in each group were killed after Weeks 13, 26, and 52. For the dog study, four male and four female beagle dogs were alloted to each group and treated with the compound at 0, 0.4, 4, and 40 mg/kg/day for 104 weeks. The dogs in the 40 mg/kg/day group had severe toxic signs, including nausea or vomiting, salivation, and occasional clonic convulsion, and all were subjected to unscheduled necropsy before Day 203 of treatment. The dogs also had ophthalmological changes such as fundal hemorrhage, miosis, and desquamation of the retina which were consistent with the retinal lesions shown by histopathology. The rats of the high-dose group had retarded growth with a slightly decreased food intake. Anemia was evident in high-dose female rats and in middle- and high-dose dogs. Liver failure in male and female dogs and kidney damage in female dogs were detected in middle- and high-dose groups by blood biochemistry and/or histopathology. Regressive changes of the sciatic nerve accompanied by atrophy of the calf muscle were seen in female rats of the high-dose group but not in male rats. In high-dose rats, progression of myocardial lesions of the heart and chronic nephrosis of the kidney were depressed in males and females, respectively. Female rats of the middle- and high-dose groups had decreased occurrences of mammary fibroadenoma and decreased development of skin masses.

Animals↗
PubMed1991

Metabolic induction of the hepatic cytochrome P450 system by chlorfenvinphos in rats.

Previous studies have shown that a single oral pretreatment of rats with the organophosphorus insecticide 2-chloro-1-(2,4-dichlorophenyl)vinyl diethyl phosphate (chlorfenvinphos, CVP) afforded protection against the toxicity of a subsequent challenge with the same compound within 24 hr. This protection may be due to the reduction in brain cholinesterase inhibition caused by the decrease in plasma CVP concentration. The purpose of this study was to investigate the mechanism of the decrease in plasma CVP concentration in relation to metabolic induction. CVP was preferentially metabolized by a liver microsomal fraction with an NADPH-generating system, compared with serum or kidney subcellular fractions. A single oral 24-hr pretreatment with CVP (15 mg/kg) increased the oral LD50 of its next dosage to threefold. The same treatment also increased CVP metabolism (to 178%), cytochrome P450 content (to 130%), cytochrome P450 reductase activity (to 130%), cytochrome b5 content (to 121%), and cytochrome P450-linked activities such as aminopyrine demethylase (to 140%) and aniline hydroxylase (to 127%) in the hepatic microsomal fraction. A single oral 24-hr pretreatment of phenobarbital (50 mg/kg), which is known as an inducer of cytochrome P450, increased the oral LD50 of CVP and all the related metabolic parameters listed above in an order of magnitude similar to that of CVP, although the increments induced by the phenobarbital treatment were greater than those induced by the CVP treatment. These results indicate that the increase in hepatic CVP metabolism may be due to the induction of the hepatic cytochrome P450 system caused by the single oral short-term treatment with CVP. This induction may be one of the reasons for the decrease in plasma CVP concentration which may be responsible for the reduction in toxicity of its next dosage.

Animals↗
PubMed1991

Alterations in catecholamine release in the central nervous system of spontaneously hypertensive rats.

The aim of the present study was to investigate alterations in catecholamine release in the central nervous system of spontaneously hypertensive rats. Slices of hypothalamus, medulla oblongata and striatum were prepared from spontaneously hypertensive rats (SHR: 9-10 weeks old) and age-matched Wistar Kyoto rats (WKY). The slices were incubated with (3H)norepinephrine (NE) or (3H)dopamine (DA), superfused with Krebs-solution in vitro, and the release of the catecholamines was compared between the two strains. The basal release of hypothalamic (3H)NE did not differ between SHR and WKY slices. However, stimulation (1 Hz)-evoked (3H)NE release was significantly greater in SHR than in WKY (percent fractional release of total tissue NE: WKY 0.494 +/- 0.019%, n = 6, SHR 0.730 +/- 0.053%, n = 6, p less than 0.05). The stimulation-evoked (3H)NE release from the medulla oblongata did not differ significantly between SHR and WKY slices. Finally stimulation-evoked release of striatal (3H)DA was significantly depressed in SHR (percent fractional release of total tissue DA: WKY 2.048 +/- 0.24%, n = 6, SHR 1.460 +/- 0.068%, n = 6, p less than 0.05). These results indicate that the release of hypothalamic NE and striatal DA are altered in SHR. It is suggested that enhanced hypothalamic noradrenergic activity and reduced striatal dopaminergic activity can increase sympathetic outflow to the periphery, which may play a role in the pathogenesis of this form of hypertension.

Animals↗
PubMed1991

[Clinical evaluation of a combination treatment with cefminox and fosfomycin for infections complicated in patients with hematological disorders].

We evaluated clinical effects and toxicities of a combination treatment with cefminox (CMNX) and fosfomycin (FOM) for infections complicated with hematological disorders in 56 patients. Among those, 52 patients including 22 with malignant lymphoma, 19 with acute leukemia, and 11 with other hematological disorders were evaluable. Excellent and good responses were obtained in 33 (63.5%) of the 52 patients. This treatment was also effective in 5 of 9 cases in which granulocyte counts were less than 500/mm3 through the course of administration. Side effects were observed in only one patient. Mild nausea occurred but was not serious. These results indicate that the combination of CMNX and FOM is an effective and safe regimen for the treatment of infections complicated in patients with hematological disorders.

Adult↗
PubMed1991

1H NMR study on amide proton exchange of calmodulin-mastoparan complex.

Amide proton exchange rates of Ca2(+)-saturated calmodulin and Ca2(+)-saturated calmodulin-mastoparan complex were studied by 1H NMR spectroscopy. Exchange rates of Gly25, Gly61, Gly98, Gly134, Ile27, Ile100, and Asn137 were determined for Ca2(+)-saturated calmodulin and for Ca2(+)-saturated calmodulin-mastoparan complex, and were found to be less than 10(-4)s-1. All these residues of which the amide proton resonances appear at lower fields were considered to form hydrogen bonds, based on the results of X-ray analysis. Exchange rates of Ile27 and Asn137 became an order of magnitude smaller when mastoparan bound to Ca2(+)-saturated calmodulin, while those of the four glycines and Ile100 did not change appreciably. The reduction in accessibility of Asn137 to water cased by mastoparan binding suggests that a part of the mastoparan binding site is probably located in or near the hydrophobic cluster of the C-terminal-half domain. The reduction in accessibility of Ile27 also suggests that another part of the mastoparan binding site is located in or near the hydrophobic cleft of the N-terminal-half domain.

Amino Acids↗
PubMed1991

[Clinical evaluation of imipenem/cilastatin sodium as a second line regimen in severe infections associated with hematologic disorders].

Imipenem/cilastatin sodium (IPM/CS), which has a broad spectrum of activity against both Gram-positive and -negative bacteria including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, was used as the second choice for severe infections associated with hematological disorders. Sixty-five patients were treated with IPM/CS. Among them, 53 patients were evaluable for the clinical efficacy. Twelve patients were not evaluable due to the following reasons: 5 patients were treated with combinations of other regimens such as cefzonam, cefmenoxime, ciprofloxacin or gamma-globulin, 5 were patients to whom IPM/CS was administered as the first choice, and the remaining 2 patients were thought to be suffering not from febrile infections but from febrile tumor. Excellent responses were observed in 10 (18.9%) patients and good responses in 23 (43.4%) patients, with an overall rate of efficacy of 62.3%. The efficacy in septic patients was 75% (3/4), and that in patients whose peripheral granulocytes were continuously below 100/microliter was also 75% (6/8). Two patients who suffered from tumor fever and 5 patients who had received no chemotherapy before IPM/CS administration were included in the final evaluation of side effects. Side effects were observed in 16 patients (16/60, 26.7%). In a 61 years, female patient, a skin eruption was found 4 days after IPM/CS therapy was started. In 15 patients, mild gastrointestinal symptoms such as nausea and vomiting were identified within a few days after IPM/CS treatment was started. Abnormal laboratory data such as eosinophilia, liver dysfunction or renal dysfunction were also identified in 4 patients (4/60, 6.7%). Degrees of these abnormalities were very slight, however, and the continuation of treatment was not disturbed. These results indicated that IPM/CS was an effective second line regimen of chemotherapy for the treatment of severe infections in patients with hematological disorders.

Adult↗
PubMed1990

Effects of calcitonin gene-related peptide on [3H]norepinephrine release in medulla oblongata of spontaneously hypertensive rats.

We now describe the effects of calcitonin gene-related peptide (CGRP) on [3H]norepinephrine (NE) release in medulla oblongata of spontaneously hypertensive rats (SHR). CGRP inhibited stimulation-evoked [3H]NE release in a dose-dependent manner in Sprague-Dawley rats, although the basal release of [3H]NE was not affected by the peptide. In SHR, the inhibitory effect of CGRP on stimulation-evoked [3H]NE release was significantly attenuated compared with Wistar Kyoto rats. These results suggest that CGRP might be involved in the regulation of central sympathetic nervous activity in hypertension.

Animals↗
PubMed1990

Reciprocal t(14;19)(q32.3;q13.1) in a patient with B-cell lymphoma.

A patient with B-cell lymphoma with a chromosome rearrangement of t(14;19)(q32.3;q13.1) is reported. This patient had leukemic features and an aggressive clinical course. The histopathologic diagnosis was malignant lymphoma, small noncleaved cell. Chromosome analysis of the cells from a cervical lymph node and peripheral blood showed a reciprocal translocation between chromosome 14 with a break at band q32.3 and chromosome 19 with a break at band q13.1, to which the bcl-3 gene has been mapped. Monoclonal rearrangement of the JH gene was detected by Southern blot analysis. However, we could not detect rearrangement of the bcl-3 gene. This case also had a t(2;8)(q13;q24.1), but the c-myc gene remained in its germline. This is the first case with the reciprocal t(14;19) and 8q24 chromosomal breakpoint in a B-cell lymphoid malignancy.

Chromosomes, Human, Pair 14↗
PubMed1990

Effects of neuropeptide Y on norepinephrine release in hypothalamic slices of spontaneously hypertensive rats.

We describe the effects of neuropeptide Y (NPY) on [3H]norepinephrine (NE) release from hypothalamic slices of spontaneously hypertensive rats (SHR). The electrical stimulation (1 Hz)-evoked [3H]NE release was significantly greater in hypothalamic slices of SHR than in those of Wistar Kyoto rats (WKY). NPY inhibited the stimulation-evoked [3H]NE release in a dose-dependent manner. The inhibitory effect of NPY was significantly attenuated in SHR compared with WKY. The results may indicate that the less inhibitory effect of NPY on NE release induces increased sympathetic nerve activity in the hypothalamus of SHR.

Animals↗
PubMed1990

1H NMR study of rabbit skeletal muscle troponin C: Mg2(+)-induced conformational change.

Binding of Mg2+ to rabbit skeletal muscle troponin C (TnC) is studied by means of two-dimensional (2D) 1H NMR spectroscopy. Using the sequence-specific resonance assignment method we assign several resonances of TnC in the Mg2(+)-saturated state. Assigned resonances are used as probes of the following titration experiments: (1) Mg2+ titration of apo-TnC, (2) Mg2+ titration of Ca2TnC, and (3) Mg2+ titration of Ca4TnC. In experiment 1, the slow-exchange behavior is observed for resonances of Phe99, Asp107, Gly108, Tyr109, Ile110, Asp111, His125, Gly144, Arg145, Ile146, Asp147, and Phe148 located at the high-affinity Ca2(+)-binding sites in the C-terminal-half domain. In experiments 1 and 2, the fast-exchange behavior is observed for resonances of Gly32, Asp33, Ser35, Gly68, Thr69, and Asp71 located at the low-affinity Ca2(+)-binding sites in the N-terminal-half domain. These results suggest that Mg2+ ions bind to the N domain as well as the C domain. In experiment 3, no spectral change is observed for all above-mentioned residues in the C domain and also for Gly32 and Gly68 in the N domain. It can be concluded that all Ca2(+)-binding sites in both the N and C domains can bind Mg2+ ions. No significant change is observed for resonances of Phe23, Ile34, Val68, and Phe72 in experiments 1 and 2. These results suggest that Mg2+ binding to the N domain does not induce conformational change in the hydrophobic region of the N domain. 2D-NMR spectra and Mg2(+)-titration data suggest that the antiparallel beta-sheet conformation is formed in both the N and C domains when Mg2+ ions bind to the two domains.

Animals↗
PubMed1990

cis-diamminedichloroplatinum(II)-induced sister-chromatid exchanges and chromosome aberration formation in cultured human lymphocytes and their inhibition by sodium thiosulfate.

cis-Diamminedichloroplatinum(II) (cis-DDP)-induced sister-chromatid exchanges (SCEs) and chromosome aberration formation were studied in human lymphocytes. The mitotic index decreased abruptly at 2 X 10(-6) M cis-DDP and the frequency of SCEs was dose-related; a marked increase was recorded at 10(-6) M cis-DDP. A dose-dependent effect was also found for chromosome aberration formation at concentrations between 10(-11) and 4 X 10(-6) M. The aberrations observed were primarily chromatid breaks and gaps. We also examined the inhibition of these genotoxicities by treating the cells with sodium thiosulfate (STS). Simultaneous treatment with 10(-4)-10(-3) M STS (100-1000-fold molar ratio to cis-DDP) significantly reduced the frequency of SCEs induced by 10(-6) M cis-DDP. Furthermore, a 3-h delay in treating with STS significantly reduced cis-DDP-induced SCEs, but not chromosome aberration formation.

Antioxidants↗
PubMed1990

Pretreatment of rats with an organophosphorus insecticide, chlorfenvinphos, protects against subsequent challenge with the same compound.

A single oral pretreatment of rats with chlorfenvinphos (CVP) reduced toxicity of the same compound subsequently administered. This protection occurred 8 hr and became maximal 24 hr after the oral pretreatment at a dose of 15 mg/kg (about half of its LD50). The 24-hr pretreatment with CVP increased the LD50 of CVP threefold, but did not change the type of toxic signs and time to death caused by CVP. The CVP pretreatment did not appreciably change the toxicities of the cholinergic agonists, carbachol and oxotremorine, but significantly increased the toxicity of another organophosphate, dichlorvos. Oral treatment of rats with CVP (15 mg/kg) inhibited brain acetylcholinesterase (AChE) activity. This inhibition became maximal at 4 hr (about 20% of control) and lasted more than 24 hr after the administration. Twenty-four hours after oral administration of CVP (15 mg/kg), the second dose (CVP 30 mg/kg, po) was less effective in inhibiting cholinesterase activities of the brain, erythrocyte, and plasma compared with naive rats treated with the same dose. The difference in brain AChE activity between control and CVP pretreatment groups was greater in magnitude than that measured in erythrocytes. CVP concentration in plasma after the oral administration of CVP (30 mg/kg) was decreased by the CVP pretreatment. Area under the concentration vs time curve (AUC) in the CVP-pretreated group was about one-fourth of AUC in the control group. This decrease in the AUC was comparable to the decrease in the toxicity of CVP. Thus, the protection against subsequent CVP challenge may be due to the reduction in the inhibition of brain AChE activity caused by the decrease in plasma CVP concentration.

Acetylcholinesterase↗
PubMed1990

Enhanced endogenous epinephrine release from the vascular adrenergic neurons in spontaneously hypertensive rats.

This study was performed to investigate the role of endogenous epinephrine in the regulation of vascular tone in hypertension. The release of endogenous epinephrine and norepinephrine from the vascular adrenergic neurons by periarterial nerve stimulation was examined in spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). The isolated mesenteric vasculatures were prepared, and the epinephrine and norepinephrine release during electrical nerve stimulation was determined as the increase in epinephrine and norepinephrine contents in the vascular perfusate. Epinephrine and norepinephrine were measured by high performance liquid chromatography with an electrochemical detector. Vasoconstrictor responses and norepinephrine overflow during electrical nerve stimulation were significantly greater in SHR than in WKY. The amount of stimulation-evoked epinephrine overflow into the perfusate was also increased in SHR compared to that in WKY, especially at low frequency stimulation. These results suggest that epinephrine could be released from the vascular adrenergic neurons as a cotransmitter of norepinephrine and contribute to increased vascular tone in hypertension.

Animals↗
PubMed1990

Enhanced neuroinhibitory effect of diltiazem in blood vessels of spontaneously hypertensive rats.

This study investigated the effects of diltiazem (a Ca2(+)-entry blocker) on neuromuscular junctions of blood vessels in hypertension. In isolated perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY), the effects of diltiazem on norepinephrine release from vascular adrenergic neurons and pressor responses were examined. The influences of extracellular Ca2(+)-reduction on these responses were also studied. Stimulation evoked pressor responses and norepinephrine release were significantly greater in the mesenteric vasculatures of SHR than in those of WKY. Diltiazem inhibited both pressor responses and norepinephrine release during electrical nerve stimulation in a dose-dependent manner. The suppression of these responses was more pronounced in SHR than in WKY. Reduction of extracellular Ca2(+)-concentration also decreased the responses in SHR and WKY, and the inhibitory degree was significantly greater in SHR than in WKY. These results demonstrate that diltiazem affected the presynaptic site of the mesenteric vasculatures and decreased the stimulation-evoked norepinephrine release from vascular adrenergic neurons with a concomitant reduction of pressor responses of the preparation. Furthermore, the marked inhibition of pressor responses and norepinephrine release by diltiazem or Ca2(+)-depletion in SHR may suggest the increased Ca2(+)-dependency in vascular neurotransmission in this model of hypertension.

Animals↗