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Biomedical subjects

M Ishida

Publications and source records attributed to M Ishida.

At least 19 recordsLinked to original sources

Neurotoxicity of acromelic acid in cultured neurons from rat spinal cord.

Acromelic acid A, which contains the kainic acid structure in its molecule, is known to cause selective damage of interneurons in the rat lower spinal cord. In the present study, the potent neurotoxicity of acromelic acid A was demonstrated in cultured rat spinal neurons in terms of the activity of lactate dehydrogenase that was released from degenerated neurons into the culture medium. Acromelic acid A increased the lactate dehydrogenase activity in time- and concentration-dependent manners, and its EC50 was about 2.5 microM, which was much lower than that of kainic acid (70 microM) and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (EC50; 11 microM). The maximum level of lactate dehydrogenase released by acromelic acid A was quite similar to that by kainic acid, but was about twice the level produced by (RS)-alpha-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Exposure to acromelic acid A caused release of L-glutamate from the cells into the medium; however, the concentration of L-glutamate released was far below the level for inducing the neurotoxic effects. The neurotoxicity of 10 microM acromelic acid A was almost completely inhibited by 30 microM 6-nitro-7-sulphamoylbenzo(F)quinoxaline-2,3-dione and 6-cyano-7-nitroquinoxaline-2,3-dione, potent antagonists for non-N-methyl-D-aspartate receptors, but was partly (35%) reduced by 30 microM dizocilpine maleate. In cultured hippocampal neurons, the toxicity of acromelic acid A was significantly less effective (EC50: 18 microM) than that in spinal neurons, whereas the toxicity of kainic acid was almost the same in both neurons. These results suggest that acromelic acid A directly activates non-N-methyl-D-aspartate receptors on the cultured spinal neurons to induce neuronal death. A new type of non-N-methyl-D-aspartate receptors which is specific to acromelic acid A is suggested to be present at least in spinal neurons.

Amino Acids

Inhibition of trazodone metabolism by thioridazine in humans.

To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1-18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 +/- 252 vs. 969 +/- 370 ng/ml) and m-CPP (61 +/- 22 vs. 94 +/- 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.

Adult

Dietary salt decreases cytosolic calcium in platelets from Dahl salt-sensitive rats.

To determine whether abnormal cellular Ca2+ handling is involved in salt-induced hypertension of Dahl salt-sensitive rats (DS), we investigated Ca2+ handling in fura 2-loaded platelets of DS and Dahl salt-resistant rats (DR) fed a high-NaCl (8%) or a low-NacL (0.3%) diet for 4 wk from 5 wk of age. At 5 wk of age, blood pressure, resting cytosolic Ca2+ concentration ([Ca2+]i), the thrombin-evoked increase in [Ca2+]i and the size of internal Ca2+ stores of DS were comparable with those of DR. After 4 wk on the diets, resting [Ca2+]i of DS on high-NaCl diet was lower than that of DS on low-NaCl diet, and there was no effect of high salt intake on resting [Ca2+]i in DR. In DS, high salt intake attenuated the [Ca2+]i response to thrombin in the presence of external Ca2+. In contrast, the [Ca2+]i response to thrombin in the absence of external Ca2+ was enhanced by high salt intake in DS. The size of internal Ca2+ stores was increased by high salt intake in DS but not in DR. These data suggest that it is not obligatory for hypertension to be accompanied by an increase in platelet [Ca2+]i.

Animals

Serum levels of six pancreatic enzymes as related to the degree of renal dysfunction.

OBJECTIVES: Currently, serum total amylase, pancreatic isoamylase (P-amylase), lipase, trypsin(ogen), phospholipase A2 (PLA2), and elastase I are advocated to be useful in diagnosing pancreatic diseases. However, the most useful among the above six enzymes in patients with impaired renal function has not been fully clarified. We, therefore, studied the relation of the serum levels of the above enzymes and creatinine clearance (CrCl) in normal controls and patients with chronic renal insufficiency or failure. METHODS: PLA2 and elastase I were assayed by RIA, trypsin(ogen) by EIA and others by activity. Subjects were 24 healthy controls and 47 patients with impaired renal function and no apparent pancreatic diseases. RESULTS: 1) Elastase I was significantly elevated only in patients with a CrCl of 10 ml/min or less, whereas others were elevated already in patients with a CrCl below 40 ml/min; 2) in 12 patients with a CrCl between 13 and 39 ml/min, lipase tended to be less frequently raised than others, except elastase I, although the difference was statistically insignificant; 3) in 28 patients with a CrCl between 40 and 74 ml/min, lipase was less frequently elevated than others, except elastase I and PLA2; 4) in seven patients with a CrCl of 10 ml/min or below, elastase I tended to be less frequently elevated than others, although the difference was statistically insignificant; and 5) the degree of elevation was within 2.5 times the upper limits of reference values in all enzymes, except trypsin(ogen) (within 4.8 times). CONCLUSIONS: Elastase I was least vulnerable to impaired renal function followed by lipase. We, therefore, recommend combined assays of elastase I and lipase for detecting pancreatic diseases in patients with renal insufficiency. When cut-off levels are set at 2.5 times the upper limit of reference values, P-amylase or PLA2 can replace lipase.

Aged

New, potent kainate derivatives: comparison of their affinity for [3H]kainate and [3H]AMPA binding sites.

Newly synthesized kainate derivatives, 4-(2-hydroxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (HFPA and 4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (MFPA), were potent inhibitors of [3H]kainate binding to the rat spinal cord synaptic membranes, comparable in their effectiveness to kainate and domoate, whereas acromelic acid A (ACRO-A) and B (ACRO-B) was much less effective than kainate. ACRO-A, MFPA and HFPA all inhibited [3H]AMPA binding. These novel kainate analogues provide new pharmacological tools for analyzing the mechanisms underlying activation of kainate/AMPA receptors.

Amino Acids

[Evaluation of performance in diagnosis of pneumoconiosis using FCR (Fuji Computed Radiography)].

The purpose of this study was to determine the applicability of the FCR system to the diagnosis of pneumoconiosis. In the study, images of pneumoconiosis obtained by FCR were collected from the Rosai Hospital for Silicosis, and the distribution, shape and size of small opacities of pneumoconiosis were determined by three of the authors. An image data base was prepared, and diagnosis of pneumoconiosis using FCR test films was performed by 12 physicians with reference to reduced ILO films. Among the data obtained, data relating to profusion were analyzed. The results were compared with those obtained in the previous study. It was found that, if suitable image processing was carried on FCR test films, profusion could be classified with an accuracy equal to that of the diagnosis of pneumoconiosis with usual full-size films. It was necessary to establish standard films obtained by FCR in order to improve the accuracy of diagnosis of pneumoconiosis using FCR.

Evaluation Studies as Topic

Quantitative dot blot analyses of blood-group-related antigens in paired normal and malignant human breast tissues.

Membranes were prepared from 31 breast-cancer specimens and adjacent mammary tissues, dot-blotted to nitrocellulose paper, and reacted with monoclonal antibodies (MAbs) (A, B, Lewis a, Lewis b, sialylated Lewis a, Lewis x, and Lewis y) and lectins (Ulex europaeus, peanut agglutinin) having various blood-group specificities. The expression of epithelial membrane antigen was assayed with MAb MA5. The ratio of breast-cancer to normal mammary membrane preparations (C/N ratios) of these reagents was measured by densitometric scanning. We observed a decrease in the levels of A, B, Lewis a, Lewis b, sialylated Lewis a, and Lewis y antigens and an increase of Lewis x, T, and MA5-reactive determinants in breast cancers. The incidence of incompatible A, as well as A and B, antigens was demonstrated for 2 patients of blood group B and O respectively. When the receptor content was plotted against the C/N ratio of these various reagents, a significant inverse relationship between the C/N ratio of Lewis x antigen and estrogen (ER) and progesterone receptor (PR) content was observed in breast cancers. The mean C/N ratio of Lewis x antigen was significantly higher in the ER-negative/PR-negative (ER-/PR-; 2.33 +/- 1.17), as compared with the ER-positive/PR-positive (ER+/PR+; 0.97 +/- 0.80). According to these observations, Lewis x antigen expression may be influenced by hormonal stimuli such as estrogen and progesterone.

ABO Blood-Group System

Protective effect of carteolol, a beta-blocker, on myocardial cellular damage in ischemic and reperfused pig hearts: assessment with gated in vivo 31-phosphorus magnetic resonance spectroscopy and electron microscopy.

To assess the effect of carteolol, a beta-blocker, on ischemia and reperfusion, changes in the ultrastructure of myocytes and energy metabolism were studied by 31P-NMR in 41 pig hearts without collateral circulation. The left anterior descending coronary artery was occluded for 20 min and reperfused for 120 min in three groups: seven pigs (group 1, no treatment with carteolol; group 2, pre-ischemia treatment with carteolol (10 micrograms/kg); group 3, post-ischemia treatment with carteolol before reperfusion). Other groups of five pigs were killed after 120 min of ischemia (group 4, no treatment; group 5, pre-ischemia treatment) or 20 min of ischemia (group 6, no treatment; group 7, pre-ischemia treatment). After 20 min of ischemia, ATP was higher in groups 2 (76 +/- 9% of the baseline value) than in group 1 (59 +/- 5%) and group 3 (60 +/- 10%). However, the difference disappeared after 30 min of ischemia. After 120 min of reperfusion, ATP showed much better recovery in group 2 (92 +/- 9%) than in groups 1 (66 +/- 7%) and 3 (68 +/- 10%). Ischemic injury, as viewed by light and electron microscopy, was milder in group 7 than in group 6 after 20 min occlusion, but the myocytes were almost normal after 120 min reperfusion in groups 1 to 3. The heart rate, blood pressure and rate pressure product showed no significant difference among the groups. These results indicate that pre-ischemia treatment with carteolol provided protection against ischemic cellular injury and accelerated the repletion of ATP during reperfusion, but the post-ischemia treatment did not lead to recovery of ATP. Therefore, the favorable effect during reperfusion of pre-ischemia treatment with carteolol depends on its protective effect during ischemia.

Adenosine Triphosphate

A metabotropic L-glutamate receptor agonist: pharmacological difference between rat central neurones and crayfish neuromuscular junctions.

1. 2S,3S,4S-2-(carboxycyclopropyl)glycine (L-CCG-I), a conformationally restricted glutamate analogue, is a potent metabotropic L-glutamate receptor agonist in the mammalian central nervous system. 2. Depolarizing actions of L-CCG-I and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) in the newborn rat spinal motoneurone are temperature-sensitive, and are not depressed by 3-[(+/-)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid (CPP) and/or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. L-CCG-I and trans-ACPD induced oscillatory responses in Xenopus oocytes injected with rat brain mRNA. Oocytes with oscillatory responses to L-CCG-I and trans-ACPD showed reversal potential of about -20 mV, which was very close to the equilibrium potential of chloride ions. 4. In rat hippocampal synaptoneurosomes, L-CCG-I stimulated phosphoinositide hydrolysis in a concentration dependent manner. L-CCG-I was less potent than quisqualate but more potent than trans-ACPD. 5. At low concentrations, L-CCG-I did not cause any depolarization of newborn rat spinal motoneurones, but reduced substantially amplitudes of monosynaptic reflexes. 6. At the crayfish neuromuscular junction L-CCG-I, acting presynaptically, reduced the amplitude of excitatory junctional potentials. This action was prevented by application of picrotoxin but not pertussis toxin. The actions of trans-ACPD differ from those of either L-CCG-I or ibotenate at the crayfish neuromuscular junction. 7. L-CCG-I has a potential to provide further useful information on metabotropic L-glutamate receptor function.

Amino Acids, Dicarboxylic

Effects of zonisamide on extracellular levels of monoamine and its metabolite, and on Ca2+ dependent dopamine release.

The effects of zonisamide (3-sulfamoylmethyl-1,2-benzisoxazole), a novel anticonvulsant, on extracellular levels of monoamine and its metabolite in the striatum and hippocampus, and Ca2+ dependent monoamine release in the striatum of freely moving rats were studied by microdialysis. Zonisamide increased dopamine, homovanillic acid and 5-hydroxyindoleacetic acid, and decreased 3,4-dihydroxyphenylacetic acid in the rat striatum. However, zonisamide showed no effect on Ca2+ dependent dopamine release in the rat striatum. In the hippocampus, zonisamide increased dopamine, homovanillic acid, serotonin and 5-hydroxyindoleacetic acid and decreased 3,4-dihydroxyphenylacetic acid. The present results suggest that zonisamide facilitates dopaminergic and serotoninergic neurotransmission but does not affect Ca2+ dependent dopamine release within therapeutic plasma concentrations.

3,4-Dihydroxyphenylacetic Acid

Impact of influenza virus infection as a cause of pediatric hospitalization.

From winter 1989 to spring 1990, a severe epidemic caused by influenza A (H3N2) and B viruses developed in Japan. During the epidemic (December 1989 to February 1990), 244 children were admitted to the pediatric ward of Nippon Kokan Hospital: 53 (21.7%) were hospitalized with influenza virus infection, 22 (9.0%) with rotavirus gastroenteritis, and 17 (7.0%) with respiratory syncytial virus infection. Among those with influenza, 24 had type A and 29 had type B. Most were young healthy children without underlying illnesses (mean age, 4.8 +/- 3.4 years). The impact of the influenza epidemic on pediatric hospitalization is probably much greater than generally thought when a severe epidemic occurs.

Adolescent

Origin and evolutionary characteristics of antigenic reassortant influenza A (H1N2) viruses isolated from man in China.

During the 1988/1989 influenza season, five antigenic reassortant influenza A (H1N2) viruses not previously isolated from man were isolated in Hebei province, People's Republic of China. All isolates contained haemagglutinins (HAs) and neuraminidases (NAs) which were antigenically similar to those of the recent Russian (H1N1) and Hong Kong influenza A (H3N2) viruses, respectively. The results of antigenic and nucleotide sequence analyses revealed that the genes encoding the polymerase, nucleoprotein, NA, matrix and non-structural proteins of the reassortant A/Hebei/24/89 (H1N2) virus were derived from the H3N2 parent virus, whereas its HA gene was from the H1N1 parent virus. The nucleotide sequences of the HA (encoding the HA1 subunit) and NA genes of the reassortant viruses were also determined. Phylogenetic trees constructed from these data by the neighbour-joining method revealed that the HA gene of the reassortant virus was closely related to those of recent human H1N1 viruses, whereas the NA gene was related to a recent human Hong Kong (H3N2) virus lineage.

Antigens, Viral

Progression of carotid atherosclerosis in Japanese patients with coronary artery disease.

BACKGROUND AND PURPOSE: Along with the recent changes in lifestyle in Japan, the incidence of coronary artery disease has increased while the incidence of stroke appears to be decreasing. We investigated the relation between the progression of carotid atherosclerosis and the severity of coronary artery disease in the Japanese population. METHODS: The 2-year change in extracranial carotid atherosclerosis in 50 Japanese patients who underwent coronary angiography was evaluated using carotid echotomography. To quantify the extent of carotid atherosclerosis, the maximal thickness measurements of all plaques were summed for an individual plaque score, except for new plaques found on reexamination. Carotid disease progression was evaluated by the sum of plaque score change and the thickness of the new plaque found on reexamination. RESULTS: The plaque score changed by -3.2 to 10.1 mm (mean +/- SD, 1.06 +/- 2.42 mm). The extent of coronary atherosclerosis (p less than 0.02) and serum total cholesterol level (p less than 0.01) were different between the progressing (n = 17) and the nonprogressing (n = 30) groups of carotid atherosclerosis when the progressing group included the patients with a delta plaque score of greater than or equal to 1.0 mm. Neither age, serum triglyceride level, serum high-density lipoprotein cholesterol level, pack-years of smoking, percentage of smokers, percentage of hypertensive patients, nor percentage of diabetic patients was different between the two groups. Carotid disease progression was significantly higher in patients with three-vessel coronary disease than in patients without significant coronary artery disease (p less than 0.005). There was a significant positive linear correlation between carotid disease progression and Gensini's coronary artery disease score (R = 0.411, p less than 0.005). CONCLUSIONS: Our data showed that severe coronary artery disease and a high serum total cholesterol level were strong predictors for carotid disease progression in Japanese patients with high rates of coronary artery disease.

Carotid Artery Diseases

Nematocidal activity of long alkyl chain amides, amines, and their derivatives on dog roundworm larvae.

The nematocidal activity of amides and amines having a long alkyl chain against the second-stage larva of dog roundworm, Toxocara canis, was examined. Long chain acyl amides with smaller substituents on the nitrogen showed stronger activity and the activity of cyclic amine amides was stronger than that of acyclic ones. In a series of homologous amides, the activity was dependent on the alkyl chain length: it reached a maximum at an optimal chain length and decreased in both shorter and longer homologues. The relationship between the activity and hydrophobicity of the homologues was analysed by the use of the bilinear model. The hydrophobicity of a compound, which gives a maximal activity, was similar for all neutral amides, but amides which have an additional amine group in the molecule had different values. Tertiary amines and their salts having a long alkyl chain also showed nematocidal activities comparable to those of the corresponding amides. The salts killed the larva at concentrations lower than their critical micell concentration, suggesting that they behave as a single molecule for the nematocidal action.

Amides

A case of malignant lymphoma accompanied by Klinefelter's syndrome.

A 66-year-old Japanese male with diffuse non-Hodgkin's lymphoma, of the pleomorphic type, complicated with Klinefelter's syndrome is reported. His phisique was characterized by a long arm span, disproportionately longer lower body dimensions and a small sized penis. He had no children. Chromosomal study revealed 47, XXY and hormonal quantification showed hypergonadtropic hypogonadism. Although chemotherapy was administered, his disease took a progressive course and he died. A discussion of chromosomal alteration and oncogenesis and review of the literature are included.

Aged

Inflammatory pseudotumor of the spleen.

The case of a 39-year-old man with inflammatory pseudotumor of the spleen is presented. This is an extremely rare benign lesion with histologic features of non-specific inflammatory and reparative changes. The literature is reviewed and this case is compared clinically and radiologically with the previously reported cases.

Adult

[A case of complete recanalization in the lower abdominal aorta by intraaortic infusion of a thrombolytic agent].

Intraarterial infusion of thrombolytic agent is useful in the treatment of obstructive arterial diseases in various vessels. However, few studies have shown that this treatment is useful for aortic occlusion. We report the case with complete recanalization in the lower abdominal aorta following intraaortic infusion of a thrombolytic agent. A 59-year-old man was admitted because of weakness and pain in the bilateral lower limbs at rest. Aortography showed complete occlusion of the abdominal aorta proximal to the inferior mesenteric artery. Both external arteries were supplied via rich collaterals. He was treated by intraaortic urokinase infusion of 2,100,000 units. Total recanalization in the abdominal aorta and both common iliac arteries was obtained. Intraaortic infusion of urokinase was shown to be effective treatment of occlusion in the abdominal aorta.

Aorta, Abdominal