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Biomedical subjects

Y Seto

Publications and source records attributed to Y Seto.

At least 19 recordsLinked to original sources
PubMed1997

Determination of Aconitum alkaloids in blood and urine samples. I. High-performance liquid chromatographic separation, solid-phase extraction and mass spectrometric confirmation.

Determination of four toxic Aconitum alkaloids, aconitine, mesaconitine, hypaconitine and jesaconitine, in blood and urine samples has been established using high-performance liquid chromatography (HPLC) combined with ultraviolet absorbance detection, solid-phase extraction and mass spectrometry (MS). These alkaloids were hydrolyzed rapidly in alkaline solution (half lives (t1/2) five months) and were unstable in solutions of methanol and ethanol (t1/2<one month). These alkaloids were separated on an octadecylsilica column with isocratic elution using a solvent mixture of tetrahydrofuran and 0.2% trifluoroacetic acid (14:86, v/v), which was found to be the optimal solvent of the elution systems examined. Calibration curves with UV detection were linear on injection of amounts ranging from 2.5 to 500 ng, and the limit of detection was 1 ng (S/N=3). These four alkaloids in aqueous solution were recovered almost totally by solid-phase extraction using the styrene polymer resin, Sep-Pak Plus PS-1, and were eluted using a mixture of acetonitrile and hydrochloric acid. These Aconitum alkaloids were confirmed by HPLC coupled with fast atom bombardment MS, giving their protonated molecular ions as base peaks. These alkaloids were detected by HPLC with UV detection from blood samples spiked with more than 50 ng ml(-1) of alkaloids, but were not detectable from urine samples spiked with 5 microg ml(-1) of alkaloids because of severe sample interference.

Aconitine↗
PubMed1997

Nicotinamide derivatives as a new class of gastric H+/K(+)-ATPase inhibitors. 1. Synthesis and structure-activity relationships of N-substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides.

A new series of N-Substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides 7 and 8 were synthesized. Upon acid activation in the acidic environment of the parietal cell, these compounds are converted into their active forms, 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines 5, which inhibit gastric H+/K(+)-ATPase. Inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cAMP in isolated rabbit parietal cells in vitro and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration in vivo were evaluated, and the structure-activity relationships were examined. Among the compounds synthesized, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridyl)nicotinamide (8b) showed potent inhibitory activities in vitro and in vivo equivalent to those of omeprazole, a typical H+/K(+)-ATPase inhibitor. Moreover, 8b was much more stable at neutral and weakly acidic pH than omeprazole, lansoprazole, and pantoprazole. Compound 8b is considered to be a promising agent for treating acid-related gastrointestinal disorders.

Aminopyrine↗
PubMed1997

Impact of lymph node metastasis on survival with early gastric cancer.

The impact of lymph node metastasis on the survival of early gastric cancer (EGC) cases remains controversial. A retrospective study of 621 patients with EGC undergoing gastrectomy with lymphadenectomy during the period 1966-1993 was performed to evaluate the influence of node involvement on long-term outcomes. Lymph node metastasis was observed in 63 cases (10.1%). Two groups, EGC with and without node involvement, were compared with respect to long-term results and various clinicopathologic factors. The median observation period was 123 months. EGC cases without metastatic nodes had significantly better outcomes than those with node involvement in terms of overall survival as well as survival excluding deaths due to diseases unrelated to the primary EGC. Survival rates for EGC patients with node involvement did not, however, differ significantly according to the number of metastatic nodes. Three factors-submucosal invasion, large tumor size, and recurrence-were significantly related to lymph node metastasis. Age, sex, family history of malignancy, histologic type, and multiple occurrence of gastric cancer were unrelated to the prevalence of node involvement. The frequency of recurrence in EGC cases without node involvement was low (1.8%, 10 of 558). Recurrence was not, however, exceptional in those with metastatic nodes (9.5%, 6 of 63). EGC patients with lymph node metastasis, even with only a single positive node, constitute a high risk group for EGC recurrence.

Aged↗
PubMed1997

The possible role of remnant-like particles as a risk factor for sudden cardiac death.

Postmortem plasma lipid and lipoprotein levels were analyzed in two groups of Japanese subjects who died suddenly and unexpectedly due to cardiac (n = 93) or non-cardiac (n = 26) causes. No individuals in either group had a significant medical or cardiac history. In this study, we measured plasma total cholesterol, triglycerides, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, and especially triglyceride-rich lipoprotein remnants. Triglyceride and apo E-rich remnant-like particles (RLP) were studied as a possible risk factor for sudden cardiac death in relation to the progression of coronary atherosclerosis. The receiver-operating characteristic curve (ROC) analysis showed that RLP-TG was the most significant risk factor for sudden cardiac death among the lipids and lipoproteins and RLP-C was the best predictor for coronary atherosclerosis. HDL-C and LDL-C levels were within normal limits in the majority of the cases and did not appear to relate to the sudden cardiac death. Apo E phenotyping was performed for the detection of the genetic background in the lipid metabolism. The frequency of the Apo E3/3 (wild type) phenotype, which closely relates with the remnant metabolism, was significantly reduced in the sudden cardiac death group. Our study on the postmortem plasma lipid analysis suggested that RLP-C and RLP-TG are the best risk predictor for coronary atherosclerosis and sudden cardiac death, respectively.

Adult↗
PubMed1997

Effects of alpha 2-adrenergic agonism, imidazolines, and G-protein on insulin secretion in beta cells.

It is well known that alpha 2-adrenergic agonism inhibits insulin secretion and stimulates glucagon secretion in both animal and human studies. Recently, alpha 2-adrenergic blockers (DG-5128, MK-912, and SL 84.0418) have been studied as antihyperglycemic agents in human subjects. To clarify the action mechanism(s) of these agents, we investigated the effects of alpha 2 agonists and antagonists (10(-10) to 10(-4) mol/L) and pretreatment by pertussis toxin (PTX) on glucose-stimulated insulin secretion using the hamster insulinoma cell line HIT-T15. The imidazoline-derivative alpha 2-adrenoceptor agonists clonidine and oxymetazoline at concentrations as low as 10(-8) mol/L significantly inhibited glucose-stimulated insulin secretion by 63% and 65%, respectively (P < .01 for both). These inhibitory effects were abolished by 20-hour preincubation of these cells with PTX 100 ng/mL. The imidazoline-derivative alpha 2-adrenoceptor antagonist DG-5128 at a concentration of 10(-4) mol/L doubled insulin secretion with or without pretreatment by PTX (P < .01 for both). Furthermore, both clonidine and oxymetazoline at a high concentration of 10(-4) mol/L stimulated insulin secretion with pretreatment of the cells by PTX (P < .05 for both). These results indicate that glucose-stimulated insulin secretion is inhibited by alpha 2-adrenoceptor agonists through PTX-sensitive G-protein in HIT-T15 cells. It is also suggested that imidazoline compounds at high concentrations directly stimulate insulin secretion.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Nicotinamide derivatives as a new class of gastric (H+/K+)-ATPase inhibitors II. Synthesis and structure-activity relationships of 2[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides.

Members of a new series of 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides were synthesized and evaluated for their gastric antisecretory activity and the ability to inhibit cytochrome P450-dependent O-dealkylation of 7-ethoxycoumarin (7-EC) in rat liver microsomes. Several of the compounds synthesized exhibited potent inhibitory activities against both [14C]aminopyrine accumulation stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and histamine-induced gastric acid secretion in pylorus-ligated rats when administered intraduodenally; their inhibitory activities were equivalent to or superior to those of the parent compound [2- [(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamide] and omeprazole. Among the compounds having potent antisecretory activity in vitro and in vivo, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(2,5-dimethyl-4-pyridinyl) pyridine-3-carboxamide and 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(2,6-dimethyl-4-pyridinyl)pyridine-3 - carboxamide in particular showed lower inhibitory activity against the 7-EC deethylase than omeprazole. It seems probable that, unlike omeprazole, these compounds do not interact with a metabolism of other drugs in vivo. These compounds, therefore, are considered to be more promising candidate agents for treating acid-related gastrointestinal disorders than the parent compound reported previously.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1997

Nicotinamide derivatives as a new class of gastric (H+/K+)-ATPase inhibitors. III. Synthesis and gastric antisecretory activity of 2-[(2- and 4-aminobenzyl, and alpha-methylbenzyl)sulfinyl]-N-(4-pyridinyl) -3-pyridinecarboxamides.

A new series of 2-[(2-aminobenzyl, 4-aminobenzyl, and alpha-methylbenzyl) sulfinyl]-N-(4-pyridinyl)-3-pyridinecarboxamides. was synthesized and evaluated for gastric antisecretory activities. Several of the compounds synthesized exhibited potent inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration. In particular, the more polar diastereoisomer of 2-[(4-methoxy-alpha-methylbenzyl)sulfinyl] -N-(4-pyridinyl)-3-pyridinecarboxamide (13b) showed in vivo inhibitory activity equivalent or superior to that of omeprazole and was a more selective (H+/K+)-ATPase inhibitor than omeprazole.

Animals↗
PubMed1997

Relation between stable glycated hemoglobin A1C and plasma glucose levels in diabetes-model mice.

In an IDDM model mouse which was inoculated with a diabetogenic variant, DK-27, of encephalomyocarditis (EMC) virus, the relation between a stable glycated hemoglobin A1C (St-HbA1C) level and plasma glucose level (PGL) in the progress of diabetes was studied. The St-HbA1C level and PGL were examined every 2 weeks for 10 weeks in normal male DBA/2 and IDDM-onset mice. PGLs of normal control mice did not change, but their St-HbA1C levels were slightly increased by 0.52 to 1.03%. On the other hand, in IDDM mice, their PGLs were greatly increased (> 400 mg/dl) and hyperglycemia was maintained throughout this observation period, with their St-HbA1C noticeably increased to 3.8% according to the progress of diabetes for 10 weeks. A highly significant correlation between St-HbA1C levels and averaged PGLs for the past weeks was found in IDDM mice. To examine the reflection of St-HbA1C levels to delicately varied PGLs, we also estimated both values in IDDM mice which were treated with insulin at a minimal effective dose once a day for 4 weeks. The St-HbA1C levels in insulin-injected IDDM mice were significantly lower than those in control IDDM mice. These findings suggest that the estimation of the St-HbA1C level is useful in following up blood glucose control in a long-term therapeutical study with small laboratory animals.

Animals↗
PubMed1997

Prognostic significance of non-gastric malignancy after treatment of early gastric cancer.

BACKGROUND: The recurrence rate of early gastric cancer is low and so second malignancies developing after treatment of this cancer have potential prognostic significance. METHODS: Some 633 patients with early gastric cancer were studied. The median observation time was 123 months. To examine the characteristics of patients with early gastric cancer and subsequent malignancy, two groups of patients, those with and those without non-gastric malignancy, were compared using univariate analysis with respect to various clinicopathological factors. To determine which parameters were independently significant, computer-based multivariate discriminant function analysis was applied. To estimate the prognostic significance of non-gastric malignancy, death rates from these diseases in patients treated for early gastric cancer were compared with the mortality rates attributable to the same diseases in the general population of Japan. RESULTS: The frequency of other malignancies, 9.6 per cent (61 of 633), was significantly higher than those gastric cancer recurrence rate of 2.4 per cent (15 of 633). After treatment for early gastric cancer patients with subsequent non-gastric malignancy had a significantly poorer outcome than those free from other cancers. Lung cancers were the major neoplasms occurring after the treatment of early gastric cancer. Univariate and multivariate analysis revealed male sex to be an independent risk factor for the subsequent development of non-gastric malignancy. Comparison of mortality rates revealed that men with early gastric cancer have a higher risk of death from non-gastric malignancy than the general male population. CONCLUSION: These results suggest that systemic surveillance is particularly important for male patients after the treatment of early gastric cancer.

Age Factors↗
PubMed1997

[Potentiating effect of ethanol on alpha 1 adrenergic receptor mediated contraction of thoracic aorta from guinea pig].

Using aortic strips isolated from guinea pigs, effects of ethanol on vascular smooth muscle tonus were studied. 50mM of ethanol significantly potentiated the contractions induced by norepinephrine and phenylephrine, but did not influence those induced by KCl and clonidine. Furthermore, ethanol significantly augmented the contraction induced by phenylephrine in the presence of verapamil, and did not have any effects on the contractions induced by A23187, Ba2+, PDBu and BAY K 8644. These results indicate that ethanol potentiates the alpha 1 adrenergic receptor-mediated contraction, depending on the extracellular calcium influx via the receptor-operated calcium channel.

Adrenergic alpha-Agonists↗
PubMed1996

Studies on the N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanin e (A-4166)receptor in HIT T-15 cells. Displacement of [3H]glibenclamide.

A-4166 is a new type of oral hypoglycemic agent that does not contain a sulfonylurea moiety. To clarify the mechanism of insulin secretion by A-4166, a specific receptor for A-4166 was investigated in a hamster pancreatic beta cell line (HIT T-15), using [3H]A-4166 or [3H]glibenclamide as a ligand. The saturation binding of [3H]A-4166 to HIT cell membranes was not observed up to 10 microM. In the displacement study, unlabeled A-4166 inhibited [3H]A-4166 binding to HIT cell membranes, but glibenclamide did not. On the other hand, A-4166 inhibited [3H]glibenclamide binding to the sulfonylurea receptor (Ki = 248 nM). A-4166 inhibited 86Rb efflux from HIT cells (IC50 = 350 nM). The EC50 for insulin secretion by A-4166 was 20 microM in HIT cells when they were incubated for 30 min in Krebs-Ringer bicarbonate buffer containing 16 mM HEPES supplemented with 5 mg/mL BSA in the absence of glucose. These data demonstrate the possibility of the presence of two kinds of binding sites for A-4166: one of them is the sulfonylurea receptor, and the other might be a binding site specific for A-4166.

Animals↗
PubMed1996

Reverse transcription-polymerase chain reaction detection and sequence analysis of small round-structured viruses in Japan.

Between 1985 and 1995, mass outbreaks of acute gastroenteritis caused by small round-structured virus (SRSV), occurred in eight prefectures in Japan. Fecal samples from 59 patients ill during these outbreaks were recently examined in our laboratory by electron microscopy (EM) and by reverse transcription-polymerase chain reaction (RT-PCR). For RT-PCR, we prepared two sets of primers, a set corresponding to the polymerase region of open reading frame 1 (ORF-1) and a set corresponding to the capsid region of ORF-2 of Norwalk virus (NV). The SRSV nucleic acid detection rate with these primers was more than double that achieved with EM. Most samples found by EM to contain virus particles were also positive by PCR. When the two sets of primers were used separately, the virus detection rate differed depending on the primer used, suggesting that the viral strains examined were not genetically not homogeneous. We then selected nine strains of the virus, cloned their PCR products and analyzed their base sequences. The base sequences of these strains were compared with those of reference strains including prototype NV and Snow Mountain agent (SMA). This comparison yielded the following findings: (1) SRSVs that cause mass outbreaks of gastroenteritis in Japan are genetically variable; (2) SRSV strains that are genetically similar to SMA and SRSV-OTH 25/89/J(OTH25) are dominant in Japan, but strains similar to NV are also present in this country; and (3) a strain (MI1/94) which is genetically identical to Southampton virus (SHV) was detected. Detection of SRSV using sensitive RT-PCR and analysis of the sequences of the amplification products seems to provide a useful means of studying the molecular epidemiology of SRSV.

Adult↗
PubMed1996

Treatment of multiple early gastric cancer.

To investigate the treatment of multiple early gastric cancer, 82 cases were compared with 829 single early gastric cancers. Univariate analyses with respect to eight clinicopathological factors--age, sex, family history of gastric cancer, macroscopic appearance, histologic type, depth of tumor invasion, tumor location, and lymph node metastasis--were performed. Age, male sex, elevated and differentiated-type tumors, frequent occurrence in the lower third, and mucosal cancers were correlated significantly with multiple early gastric cancer. However, there was no significant difference in the frequency of node involvement. Multiple early gastric cancer, limited to the mucosal layer, was not associated with node involvement. Therefore, endoscopic mucosal resection may be feasible for the treatment of multiple early gastric cancer when there is no evidence of submucosal invasion in any of the lesions and none exceed 2.0 cm in diameter. Upon examination of the long-term results for patients with multiple early gastric cancer, two (3.0%, 2/66) had died of recurrence due to hematogenous spread, and one (1.9%, 1/52) had developed cancer of the remnant stomach. Other primary malignancies were observed in 12 patients (18.2%, 12/66). In particular, lung cancer was the major neoplasm occurring after gastrectomy. These results suggest the importance of systemic surveillance for the detection of other malignancies as well as cancer of the remnant stomach and recurrence after gastrectomy for multiple early gastric cancer.

Female↗
PubMed1996

Stability and spontaneous production of blood cyanide during heating.

To investigate the effects of heat on blood cyanide concentrations, in vitro experiments were performed using a headspace gas chromatographic method. Cyanide concentrations were determined for solutions of human hemoglobin (Hb) at neutrality, and for blood which was sealed in a vial and incubated at 25, 50, 63, 75 and 90 degrees C for 1 h. Spontaneous cyanide production was also measured. Nearly all of the added cyanide was recovered in both the Hb and for blood samples which were heated below 63 degrees C. Cyanide recovery in Hb decreased in a temperature-dependent manner at temperatures above 75 degrees C, and more than half of the recovered cyanide was found to be in the free form. In contrast, cyanide in blood disappeared more rapidly, and a major portion of it existed in the bound form. Cyanide concentrations in Hb solutions which were heated at 90 degrees C dropped in the two phases; a rapid initial phase, followed by a slower process. Spontaneous cyanide production was observed at temperatures above 50 degrees C for Hb and above 63 degrees C for blood. Under optimal conditions (75 degrees C heating), about 0.2 mmol of cyanide was produced per mol heme of Hb.

Chromatography, Gas↗
PubMed1996

Avascular necrosis and the Pavlik harness. The incidence of avascular necrosis in three types of congenital dislocation of the hip as classified by ultrasound.

We analysed the incidence of avascular necrosis in 101 hips of 90 infants with congenital dislocation treated with Pavlik harness and followed up for more than one year. Using ultrasonography in the flexed-abducted position the hips were classified as type A when the femora head was displaced posteriorly, but within the socket and making contact with the posterior inner wall of the acetabulum; type B when it was in contact with the posterior margin of the acetabulum, with its centre at this level or anterior to it; and type C when it was displaced out of the socket, with its centre posterior to the posterior rim of the acetabulum. Eighty-seven hips were reduced by the harness (86%), and seven of these developed avascular necrosis (8%). All 69 hips with type-A dislocation were reduced and only one (1.4%) showed slight avascular necrosis. Eighteen (78.3%) of 23 hips with type-B dislocation were reduced, and six developed avascular necrosis (33.3%). In one hip, the femoral head was severely damaged. None of the nine hips with type-C dislocation was reduced in the harness. We concluded that the Pavlik harness is indicated for type-A but not for type-B or type-C dislocations.

Contraindications↗
PubMed1996

An autopsy case of traumatic sinus thrombosis.

A 38-year-old male slipped accidentally and fell from a height of 4.6 m, and was admitted to a hospital. A radiograph indicated a linear fracture of the parietal bone across the sagittal sutura, and a computed tomography scan of the head showed severe subdural hematoma on both parietal sides, so an operation was performed to remove the hematoma. Five hours after the operation, brain death due to a cerebral herniation occurred, and he died six days later. Autopsy revealed a linear fracture of the parietal bones, which crossed obliquely the sagittal sutura. A slightly lacerated wound of the dura mater was seen on the sagittal sutura, from where the latter half of that point to the left and right transverse sinuses were occluded completely with thrombosis. The brain was markedly swollen. From these findings, the victim was considered to have died from acute cerebral swelling due to traumatic thrombosis of the superior sagittal sinus.

Adult↗