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Biomedical subjects

K Saeki

Publications and source records attributed to K Saeki.

At least 199 records · Page 11Linked to original sources

Sympathetic denervation of the epicardial border zone in the genesis of dispersion of refractoriness and arrhythmogenesis in a 7-day-old canine myocardial infarction model.

BACKGROUND: The purpose of this study was to clarify whether sympathetic denervation occurs in the infarcted heart and contributes to the dispersion of the effective refractory period (ERP) and arrhythmogenesis. METHODS: ERP was measured at 47 epicardial sites in 13 dogs with 7-day-old infarctions after proximal ligation of the left anterior descending artery. To delineate the sympathetic innervation, the effects of ansae subclaviae stimulation (ASS), norepinephrine infusion, and prazosin infusion on ERP were tested. RESULTS: The per cent change in ERP (delta ERP) induced by ASS was significantly lower at test sites where the surviving epicardial myocardial thickness (Th) was 2 mm or less than at those with a Th of more than 2 mm and the normal zone. Eleven out of 179 sites (6.1%) overlying the infarct showed no ERP change after ASS. ASS paradoxically prolonged ERP at 29 sites (16.2%). In contrast, norepinephrine infusion produced a greater delta ERP in the infarct zone than in the normal zone. Prazosin shortened ERP at sites where ASS prolonged it, but had no effect at sites where ASS shortened ERP. ASS increased both the degree of ERP dispersion and inducibility of ventricular tachycardias or ventricular fibrillation (VT/VF), whereas norepinephrine increased VT/VF inducibility despite a reduction in ERP dispersion. CONCLUSIONS: We conclude that heterogeneous sympathetic denervation contributed to a prolongation and dispersion of ERP in the surviving epicardium overlying the infarct. Furthermore, a supersensitive response to norepinephrine with resultant ERP shortening and a paradoxical ERP prolongation during ASS caused by alpha-receptor mechanisms that may be related to increased electrical instability were observed.

Animals↗

Survival rate after vitreous surgery in patients with diabetic retinopathy.

We studied factors affecting the survival rate after vitreous surgery in 73 patients with diabetic retinopathy, who had undergone vitreous surgery between 1982 and 1987, according to the life-table theory and multivariate analysis. The 5-year survival rate was 84.8%; the mean age at death was 62.1 +/- 7.1 (mean +/- SD) years; the mean postoperative survival time was 34.0 +/- 25.2 months; the most common cause of death having been cardiovascular disease, which occurred in 5 of the 13 (38.5%) patients who had died. Patients with triopathy essentially require very careful systemic management, because this state was definitively associated with a decline in postoperative survival.

Aged↗

Metabolism of mutagenicity-deprived 3-fluoroquinoline: comparison with mutagenic quinoline.

3-Fluorinated quinoline (3FQ), a non-mutagenic derivative of the potent mutagen quinoline, was metabolized with a microsomal enzyme fraction isolated from the 3-methylcholanthrene-treated rat liver. The metabolites were 3-fluoro-5,6-dihydroquinoline-5,6-trans-diol (72%), 3-fluoroquinoline 1-oxide (6%), 3-fluoro-5,6-dihydroquinoline-5,6-cis-epoxide (1%), and 4 unidentified metabolites (11%). Since this metabolic pattern is similar to that obtained with unfluorinated quinoline, the epoxidation of the benzene moieties of quinoline and 3-fluoroquinoline is most likely a detoxication process and not mutagenic activation.

Animals↗

Effect of a new psychoactive compound, MCI-225, on brain monoamine metabolism in rats.

Effect of MCI-225 on brain monoamine metabolism was examined in rats. MCI-225 (30 mg/kg, p.o.) had no influence on noradrenaline (NA) levels, but significantly inhibited the NA turnover in the hippocampus and hypothalamus. This compound also significantly increased the 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine ratio in the cerebral cortex, hippocampus and striatum; and it enhanced the probenecid-induced 5-HIAA accumulation in the striatum. In the microdialysis study, MCI-225 markedly increased the NA output, but decreased the 3,4-dihydroxyphenylethyleneglycol output from the hypothalamus of urethane-anesthetized rats. These results suggest that MCI-225 enhances both noradrenergic and serotonergic function by inhibiting NA uptake and accelerating 5-HT turnover, respectively.

Animals↗

The occurrence of monocytoid B-lymphocytes in autoimmune disorders.

Occurrence of monocytoid B-lymphocytes (MBL) in extranodal organs in various inflammatory diseases was examined. MBL were present in 5 (11.4%) of 44 patients with Graves' disease, 11 (36.7%) of 30 with Hashimoto's thyroiditis, 1 (8.3%) of 12 with lymphoid follicular hyperplasia (LFH) of stomach, 1 (10%) of 10 with cutaneous LFH, and 0 of 5 with LFH of lung. The MBL presented as irregularly shaped nodular collections of cells, directly surrounding secondary follicles. Immunohistochemistry revealed a B-cell nature of these cells which expressed the following antigens; CD3-, CD 15-, CD45RA+, CD45Ro-, CDw 75+, CD74+, Mx-PanB+, MB-1+, EMA-. There were no immunoglobulin light chain restriction among infiltrating lymphoid cells. MBL in 2 of 18 cases showed positive reaction for CD43. The patients with MBL were older than those without MBL in each organ site, though the difference was not statistically significant. These findings showed that the MBL could appear in nonlymphoid organs affected by long-standing inflammation. High frequency of the appearance of the MBL in Hashimoto's thyroiditis suggest that MBL proliferation correlates with an impaired immune status.

Adult↗

Nucleotide sequence and genetic analysis of the region essential for functional expression of the gene for ferredoxin I, fdxN, in Rhodobacter capsulatus: sharing of one upstream activator sequence in opposite directions by two operons related to nitrogen fixation.

Nucleotide sequencing of the region upstream of two ferredoxin genes, fdxC and fdxN, of Rhodobacter capsulatus revealed the existence of one open reading frame (ORF), ORFU1, in the same orientation as these genes and two other ORFs, ORFU2 and ORFU3, in the opposite orientation. Two potential -24/-12 promoters were found in front of ORFU1 and ORFU2, respectively, and there was a putative upstream activator sequence (UAS) or NifA-binding site between them. The ORFs corresponded to no known nif genes. However, analysis of their putative products showed that the product of ORFU1 (M(r) 47,912) and that of ORFU3 (M(r) 19,090) had a flavodoxin-like domain and a 2[4Fe-4S] ferredoxin-like domain, respectively, and that the product of ORFU2 (M(r) 20,424) was a hydrophobic protein with six potential membrane-spanning portions. Results of interposon mutagenesis and complementation experiments indicated that ORFU2 but not ORFU1 is essential for nitrogen fixation and that additional gene(s) essential for nitrogen fixation must be present in the unsequenced region adjacent to ORFU3. Translational fusion analysis involving lacZYA and fdxN or ORFU3 provided evidence that the putative UAS is responsible for regulation of both ORFU1-fdxC-fdxN and ORFU2-ORFU3 operons in opposite orientations, and that the control of the latter is stricter than that of the former.

Amino Acid Sequence↗

[Antiemetic efficacy of granisetron in the treatment of pediatric cancer--(1). Clinical evaluation of granisetron at a dose of 40 micrograms/kg].

Seventeen children with various types of cancer were studied on the effectiveness of antiemetic drug, granisetron, by a crossover randomized trial; receiving granisetron (40 micrograms/kg; n = 53) or conventional antiemetics, during intensive chemotherapy. In the patients given granisetron nausea and vomiting were well controlled (83.0%), compared with 33.3% of conventional (non granisetron) group. The mean number of vomiting episodes for each 6h-period over 24h after chemotherapy was reduced markedly in the patients given granisetron, compared with conventional therapy. One patient developed paraesthesia of the hand after injection of granisetron as the adverse effect, which recovered to normal spontaneously after 3 hrs. Our data indicated that antiemetic effect of granisetron was superior to conventional antiemetic drugs, both in terms of clinical effectiveness and usefulness.

Adolescent↗

[Antiemetic efficacy of granisetron in pediatric cancer treatment--(2). Comparison of granisetron and granisetron plus methylprednisolone as antiemetic prophylaxis].

A crossover clinical trial was carried out to compare the effectiveness and safety of granisetron alone (40 micrograms/kg) with that from a combination of granisetron plus methylprednisolone (MPL, 10 mg/kg) for control of emesis and vomiting induced by anticancer drugs in children with cancer. Complete control of emesis and vomiting were achieved in 95% (19/20 cases) of patients receiving the combination compared to 85% (17/20 cases) of patients receiving granisetron alone. There were no clinical toxicities or side effects in either treatment group. These data indicated that the combination of granisetron plus MPL was superior for control of emesis and vomiting in children receiving cytostatic anticancer drugs.

Adolescent↗

Detection of low copy numbers of Epstein-Barr virus by in situ hybridization using nonradioisotopic probes prepared by the polymerase chain reaction.

A highly sensitive in situ hybridization procedure was established using digoxigenin-11-dUTP-labeled probes that were prepared by the polymerase chain reaction (PCR). By using 12 sets of primers, BamHI-W fragment of the Epstein-Barr Virus (EBV) was amplified with labeled substrate in individual PCRs. Then the 12 probes (average size, 120 base pairs) were mixed and hybridized with cultured and RNase-treated Namalwa cells, which contain two copies of EBV genomes per cell. The strength of the signals was much stronger as compared with random-primed probe. Our results indicate that the size-averaged PCR probes magnified the sensitivity for detecting low copy numbers of virus genomes by in situ hybridization and that this technique has the potential for investigating latent virus infection in other clinical situations.

Base Sequence↗

Microdialysis study of the effects of sedative drugs on extracellular histamine in the striatum of freely moving rats.

The effects of some sedative drugs on the extracellular concentration of histamine (HA) in the striatum of conscious freely moving rats were examined by in vivo microdialysis coupled with high-performance liquid chromatography-fluorometry. The HA output did not significantly change until 4 hr after intraperitoneal saline injection. Pentobarbital (46 mg/kg i.p.) significantly decreased the HA output by 76% at 0.5 to 1 hr after treatment. Muscimol (5 mg/kg i.p.) and diazepam (20 mg/kg i.p.) also significantly decreased the HA output at 0.5 to 1.5 hr after treatment. delta 9-Tetrahydrocannabinol (5 mg/kg i.p.) induced biphasic changes in the HA output, i.e., a significant increase and a significant decrease were observed at 0 to 0.5 hr and 1.5 to 2.5 hr after treatment, respectively. Reserpine (5 mg/kg i.p.) significantly increased the HA output by 47% to 58% at 0 to 2 hr after treatment. The HA output decreased to a level below 10% of the basal value by 4 hr after treatment with (S)-alpha-fluoromethylhistidine (77 mg/kg i.p.). Reserpine slightly restored the HA output (to about 25% of the original basal value). These results, taken together with our previous results, suggest the following: 1) pentobarbital, muscimol and diazepam inhibit HA release; 2) tetrahydrocannabinol initially increases HA release for a short period but markedly decreases the release thereafter; and 3) reserpine increases the extracellular HA concentration probably as a result of inhibition of its elimination.

Animals↗

Suppressive effects of the endothelin receptor (ETA) antagonist BQ-123 on ET-1-induced reduction of lipoprotein lipase activity in 3T3-L1 adipocytes.

Endothelin (ET)-1 reduced heparin-releasable lipoprotein lipase (LPL) activity in 3T3-L1 adipocytes in a concentration-dependent manner. However, a selective ETB receptor agonist, [Ala1,3,11,15]ET-1, did not act like ET-1. The ET-1-induced decrease in LPL activity was suppressed by a selective ETA receptor antagonist, BQ-123: the concentration-response curve for the ET-1 reduction of LPL activity was shifted to the right in the presence of BQ-123 in a concentration-dependent manner. This antagonistic effect of BQ-123 clarifies that the ETA receptor is responsible for the ET-1-induced reduction of LPL activity in 3T3-L1 adipocytes, which suggests that there is therapeutic potential for ETA antagonists in LPL-related lipoprotein disorders.

3T3 Cells↗

Distribution of histologic subtypes and sex ratio in various primary sites of lymphocytic lymphoma.

To examine the distribution of histologic subtypes and sex ratio in each primary site of lymphoma, 1,169 histologically proven cases of lymphocytic lymphoma were analyzed. The location of tumor was nodal in 615(53%) and extranodal in 517(44%), patients with the gastrointestinal tract being the most common. The incidence was predominantly in males for all histologic types and in nodal and extranodal sites, except for a predominance of females in extranodal lymphoplasmacytic(Lp-cytic), lymphoplasmacytoid(Lp-cytoid) tumors. Frequency of the Lp-cytic/Lp-cytoid type among all types of lymphoma in females was about 2.7 times more frequent in extranodal than in nodal sites. The most striking example was thyroid lymphoma in which the frequency of Lp-cytic/Lp-cytoid type was 36% in female and 0% in male patients. Including this type of lymphoma, frequency of low grade lymphoma in females was higher in extranodal sites than in nodal sites.

Adolescent↗

Inhibition of histamine turnover by 8-OH-DPAT, buspirone and 5-hydroxytryptophan in the mouse and rat brain.

The effects of 5-hydroxytryptamine (5-HT) receptor agonists on histamine turnover in mouse and rat brains were examined. The histamine turnover rate was estimated from the accumulation of tele-methylhistamine 90 min after i.p. injection of pargyline (65 mg/kg). In whole mouse brains, the histamine turnover was significantly inhibited by the 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (greater than 0.5 mg/kg) and buspirone (greater than 2 mg/kg) injected s.c. 10 min before pargyline treatment. 5-hydroxytryptophan (20 mg/kg) also significantly inhibited histamine turnover. Injections of the 5-HT1B agonist m-trifluoromethylphenylpiperazine (10 and 20 mg/kg) or the 5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1, 2 and 5 mg/kg), however, did not affect histamine turnover. The inhibitory effect of 8-OH-DPAT (1 mg/kg) on histamine turnover was significantly antagonized (by 40%) by pindolol (20 mg/kg) and slightly antagonized (by 29%) by spiperone (10 mg/kg), while methysergide (20 mg/kg) and ketanserin (10 mg/kg) demonstrated no antagonistic effects. 8-OH-DPAT (0.3 and 1 mg/kg) also showed an inhibiting effect on histamine turnover in various regions of rat brains. Although the extent of inhibition was slightly larger in the striatum and cerebral cortex, there was no marked regional difference. These results suggest that histaminergic activity in the brain is regulated by 5-HT1A receptors.

5-Hydroxytryptophan↗

Effect of long-term cigarette smoke exposure on locomotor activity and brain monoamine levels in rats.

Rats were chronically exposed to cigarette smoke for 20 min twice daily using a smoking machine. On days 1, 4, and 14, locomotor activity and rearing were measured for 15 min in an open-field apparatus. On day 1, exposure to cigarette smoke increased locomotor activity and rearing in the latter half of the observation period. This effect became more pronounced on days 4 and 14. Chronic cigarette smoke exposures for 21 days significantly decreased the norepinephrine levels in the hypothalamus, thalamus, and pons-medulla, but not the levels of dopamine, 5-hydroxytryptamine, or their metabolites. These results suggest that repeated cigarette smoke exposure increasingly stimulates locomotor activity and rearing and affects norepinephrine metabolism, especially in the brainstem.

Animals↗

Direct evidence for increased continuous histamine release in the striatum of conscious freely moving rats produced by middle cerebral artery occlusion.

Extracellular histamine in the stratum of conscious freely moving rats collected by intracerebral microdialysis 1 day after implantation of a U-shaped dialysis probe was measured by HPLC coupled with postcolumn o-phthalaldehyde derivatization fluorometry. The basal fractional histamine outputs were almost constant from 1 to 7 h after the start of perfusion (5.9-8.4 pg/30 min). Depolarization by perfusion with a high K+ (100 mM)-containing medium produced a significant (124%) increase and neuronal blockade by perfusion with a tetrodotoxin (1 microM)-containing medium resulted in a 68% reduction in the histamine output. The histamine output was markedly reduced by intraperitoneal injection of alpha-fluoromethylhistidine (100 mg/kg), an irreversible inhibitor of histidine decarboxylase, or (R)-alpha-methylhistamine (5 mg/kg), a potent and specific H3-receptor agonist. After middle cerebral artery (MCA) occlusion, the histamine output gradually increased, and reached four times the control value 8 h later. When rats were pretreated with metoprine (10 mg/kg), a histamine N-methyltransferase inhibitor, there was no significant difference in the histamine output between the MCA-occluded and the sham-operated groups during the first 3.5 h after the operation, but the histamine output gradually increased thereafter in the MCA-occluded group. In rats treated with alpha-fluoromethylhistidine, MCA occlusion failed to cause an increase in the histamine output. These results demonstrate that MCA occlusion induces a long-lasting increase in neuronal histamine release in the rat striatum.

Animals↗

Malignant lymphoma of the breast. Immunologic type and association with lymphocytic mastopathy.

Clinical and pathologic findings in 19 cases of primary non-Hodgkin's lymphoma of the breast collected from several hospitals in Japan were reviewed. All patients were women (median age, 45 years) and they usually had breast masses that had recently become enlarged. The sites of the lesions were the right breast in eight cases, the left breast in eight, and both breasts in one. The locations of two masses were unknown. Lymphoma recurred in the opposite breast in three cases 14, 23, and 23 months after surgery. Histologically, diffuse large cell lymphoma was the most common form of disease (63%). One lesion was a follicular lymphoma. The so-called lymphoepithelial lesion, a characteristic finding for mucosa-associated lymphoid tissue type lymphomas, was observed in eight cases (42%). Immunohistochemical analysis revealed that all but two tumors were of B-cell type; such findings confirmed morphologically based conclusions. Histologic and immunohistochemical evidence of lymphocytic mastopathy, a recently described autoimmune disease of the breast, was found in most of the cases. Formation of lymphoid follicles in or around the tumors was found in five cases (26%). Based on these findings, it is suggested that most mammary lymphomas are B-cell tumors and they may be associated with coexisting or antecedent lymphocytic mastopathy.

Adult↗

A highly sensitive assay for histamine using ion-pair HPLC coupled with postcolumn fluorescent derivatization: its application to biological specimens.

A simple and highly sensitive method for the determination of histamine (HA) was developed using ion-pair, reversed-phase HPLC coupled with postcolumn o-phthalaldehyde derivatization fluorometry, and it was applied to the unpurified extracts of human and rat plasma, and brains of rats and mice. The HA concentrations both in the plasma and brains determined by the present method were well consistent with the values obtained by cation-exchange HPLC with postcolumn fluorescent derivatization currently in use. The present method was more advantageous than the assay using cation-exchange HPLC: (1) it was three to four times more sensitive (the detection limit was 0.5 pg of HA), and (2) it enabled the measurement of HA in samples containing (R)alpha-methylhistamine, a potent and specific H3-receptor agonist, which could not be separated from HA by cation-exchange chromatography. Using the present method coupled with intracerebral microdialysis, we found in the rat hypothalamus that (R)alpha-methylhistamine (5 mg/kg i.p.) markedly decreased the extracellular concentration of HA with a maximal effect (83% reduction) during 30-60 min after injection, suggesting that most of HA in the microdialysate fraction is neuronal in origin.

Animals↗

An orange-shaped aortic root aneurysm in aortitis syndrome with severe aortic regurgitation.

A 57-year-old man, who had undergone aorto-coronary bypass surgery 4 years before when the shape of the ascending aorta had been normal, had a unique orange-shaped aortic root aneurysm associated with severe aortic regurgitation and congestive heart failure. Replacement of the aneurysm and the aortic valve was successfully carried out, and histopathological examination revealed that the aneurysm was caused by aortitis syndrome.

Aorta, Thoracic↗