Search PubMed⌕ Search

Biomedical subjects

M Ishida

Publications and source records attributed to M Ishida.

At least 199 records · Page 11Linked to original sources
PubMed1996

Modulation of target tissue response to angiotensin II and sodium sensitivity in Japanese patients with essential hypertension.

"Non-modulators" are essential hypertensive patients who fail to modulate an adrenal response, renovascular response, or both, to angiotensin II (Ang II). The aim of the present study was to characterize "non-modulators" among Japanese patients with normal-renin essential hypertension and to determine whether non-modulation is related to sodium sensitivity of blood pressure. The increase in plasma aldosterone concentration (PAC response) and the decrease in renal plasma flow (RPF response) in response to Ang II infusion (3 ng/kg/min) were assessed in 15 Japanese patients with essential hypertension who received a high sodium diet (250 mEq/d) followed by a low sodium diet (10 mEq/d). The subjects were divided into two groups (6 modulators and 9 non-modulators) based on their ability to modulate the PAC response during sodium restriction. There was no significant difference between modulators and non-modulators in electrolyte balance or in plasma Ang II levels on either diet. Changes in the PAC response during sodium restriction were significantly correlated with the change in mean blood pressure during sodium restriction (r = -0.67, p < 0.01), while changes in the RPF response were not. RPF responses in both groups decreased during sodium restriction, although an effect on the RPF response in non-modulators was unexpected. These results suggest that non-modulators do exist among Japanese patients, but that this defect does not involve both the adrenal gland and the kidney. Apparently, only non-modulation of the adrenal response is involved in the mechanism of sodium sensitivity.

Adult↗
PubMed1996

[A case of mitochondrial encephalomyopathy (MELAS)].

Mitochondrial encephalomyopathy is a hereditary syndrome showing impairment of muscle and the central nervous system. In this disorder, the following three syndromes have been identified on the basis of characteristic symptoms: Kearns-Sayre syndrome (KSS), mitochondrial encephalomyopathy with lactic acidosis, and stroke-like episodes (MELAS), and myotonic epilepsy with ragged-red fibers (MERRF). In this report, we describe a case of mitochondrial encephalomyopathy with renal disease. A 25-year-old man was referred to our hospital in May, 1992 for evaluation of long-standing proteinuria. He had a small stature, exotropia and no pretibial edema. No mental retardation was observed. Urinary protein excretion was 2.0 g/day and urine sugar was negative. Laboratory examination revealed a serum urea nitrogen 19 mg/dl, and a creatinine value of 1.5 mg/dl. Creatinine clearance was 45.8 ml/min. His serum and spinal fluid lactate value were elevated. Biopsied muscle showed an absence of ragged-red fibers, and the presence of an A-to-G point mutation at nucleotide pari 3243 in the mitochondrial tRNA(Leu(UUR)) in peripheral blood leucocytes. He was thought to have MELAS. On the renal biopsy specimens, light microscopic examinations showed minor glomerular abnormalities with two glomerular collapses and tubulo-interstitial damage. Electron microscopic examinations showed partial thickening of the glomerular basement membrane. We report here this rare case of MELAS with renal disease, and also review seventeen cases of mitochondrial encephalopathy associated with renal disease. The existence of a relationship between mitochondrial disorder and renal damage remains obscure.

Adult↗
PubMed1996

[Evaluation of 123I-iomazenil SPECT in patients with ischemic cerebrovascular disease: comparative study with 123I-IMP SPECT].

Clinical evaluation of 123I-iomazenil, a new imaging agent for central-type benzodiazepine receptors with SPECT, was performed in patients with ischemic cerebrovascular disease. We investigated 15 patients with angiographically-proven severe occlusive lesions (occlusion or > 70% stenosis) in the unilateral carotid system. 123I-iomazenil SPECT images were compared with cerebral blood flow (CBF) images and the cerebral perfusion reserve, which were measured using the "split dose 123I-IMP SPECT method" before and after the intravenous injection of 1 g of acetazolamide. For the detection of ischemic lesions, CBF images were superior to 123I-iomazenil images based on visual analysis. Regarding the count ratio of the affected MCA territory to the non-affected (L/N), 123I-IMP was lower than 123I-iomazenil in most of the cases. In five patients showing "crossed cerebellar diaschisis" by 123I-IMP, asymmetry of the cerebellar accumulation was observed in only one patient with 123I-iomazenil, which was less prominent than with 123I-IMP. There was no significant correlation between the L/N ratio with 123I-iomazenil and the cerebral perfusion reserve in the affected MCA territory. However, in some cases showing a decreased L/N ratio (< 90%) with 123I-iomazenil, a decreased CBF with normal perfusion reserve and cerebral hemi-atrophy were observed with 123I-IMP and MRI, which suggested the influence of neuronal loss due to chronic ischemia. These results indicate that 123I-iomazenil SPECT, which provides new information regarding neuronal loss due to ischemic damage to the brain, is useful for the evaluation of ischemic cerebrovascular disease.

Adult↗
PubMed1996

[Chemotherapy for two patients with non-Hodgkin's lymphoma in hemodialysis].

There are few reports on chemotherapy of non-Hodgkin's lymphoma (NHL) in patients with chronic renal failure. Two long-term hemodialysis patients were treated for NHL with modified CHOP therapy. The plasma pharmacokinetics of adriamycin (ADR) and etoposide (VP-16) were investigated in these patients. In the first case, NHL was diagnosed in a 37-year-old male (diffuse pleomorphic, T cell type, stage I E). After 4 courses of chemotherapy, he achieved complete remission. The second case, was a 56-year-old male who was admitted to our hospital with melena and abdominal pain. A diagnosis of NHL (diffuse mixed, B cell type, stage III E) was made. Complete remission was achieved with 2 courses of chemotherapy. Levels of hematological and neurological toxicity were moderately severe but tolerable. Pharmacokinetics of ADR and VP-16 in these patients were similar to those in patients with normal renal function. These results suggested that ADR and VP-16 were effective drugs for hemodialysis patients with NHL.

Adult↗
PubMed1996

[Gastric mucosal congestion following endoscopic variceal ligation--analysis using reflectance spectrophotometry].

UNLABELLED: Endoscopic variceal ligation (EVL) has been accepted as a new treatment for esophageal varices in cirrhotic patients, and evaluated to have a lower incidence of complications compared to sclerotherapy. Sclerotherapy may increase the risk of portal hypertensive gastropathy (PHG), which is recognized to be gastric mucosal congestion due to portal hypertension in cirrhotics. However, the gastric mucosal hemodynamics after EVL has not been established yet. The aim of this study is to assess whether EVL could affect the hemodynamics of the gastric mucosa. PATIENTS AND METHODS: Eleven cirrhotic patients with severe esophageal varices, who underwent prophylactic EVL were enrolled in the trial. Age and sex-matched non-cirrhotic patients who had only gastric mucosal atrophy were entered as control to compare the mucosal hemodynamics to that of cirrhotic patient. EVL was performed as described by Stiegmann et al. The gastric mucosal hemodynamics was evaluated with both gastric mucosal blood volume (IHB) and hemoglobin O2 saturation (ISO2), which were measured by reflectance spectrophotometry during endoscopy. These parameters were measured in the three points of the stomach (gastric antrum, lower corpus and upper corpus) just before and after EVL. RESULT: In all patients with cirrhosis, mild PHG was observed endoscopically. ISO2 in cirrhotic patients was significantly lower in all points of the stomach compared with control. IHB in cirrhotic patients was not significantly different from control. ISO2 of post-EVL was significantly lower than that of pre-EVL, whereas IHB of post-EVL revealed significantly higher than that of pre-EVL. However, endoscopic grade of PHG remained mild. The hemodynamics of the mucosa two weeks after the initial EVL showed improvement of the congestion. CONCLUSIONS: The gastric mucosal hemodynamics showed increment of the gastric blood volume and decreased hemoglobin O2 saturation in cirrhotic patients, indicating that cirrhotic gastric mucosa is in congestive condition. EVL for esophageal varices makes the gastric mucosa more congestive soon after the procedure in spite of the same grade of endoscopic PHG. However, the worsened congestion improves within a few weeks.

Aged↗
PubMed1995

Frequent loss of heterozygosity at the deleted in colorectal carcinoma gene locus and its association with histologic phenotypes in breast carcinoma.

Loss of heterozygosity (LOH) at the deleted in colorectal carcinoma gene (DCC), a tumour suppressor gene that encodes a protein with high homology to the neural cell adhesion molecule, was investigated in 42 surgical specimens of primary breast carcinoma. LOH was analysed in breast carcinoma by amplifying the DNA, spanning a variable number of tandem repeats site and a restriction fragment length polymorphism site within DCC, using the polymerase chain reaction (PCR). Cell sorting was used to enrich carcinoma cells. The expression of the DCC gene was also investigated using a reverse transcription-PCR method followed by Southern blot hybridization. LOH at the DCC locus was detected in 15 (51.7%) of 29 informative cases and 10 of 13 cases having DCC-LOH showed distinct reduction or loss of DCC expression. The DCC-LOH was closely associated with certain histological phenotypes: DCC-LOH was more frequent in scirrhous carcinomas than in solid-tubular ones (P < 0.05), and was also more frequent in carcinomas with infiltration into fat tissue over the mammary gland than in those without infiltration (P < 0.05). DCC-LOH was detected in invasive lobular carcinomas (2/2), but in none of the noninvasive ductal carcinomas (0/2). These observations suggest that malignant histological phenotypes are associated with DCC-LOH.

Alleles↗
PubMed1995

Novel agonists for metabotropic glutamate receptors: trans- and cis-2-(2-carboxy-3-methoxymethylcyclopropyl)glycine (trans- and cis-MCG-I).

New derivatives of 2-(carboxycyclopropyl)glycine (CCG), (2S,1'S,2'R,3'S)- and (2S,1'S,2'R,3'R)-2-(2-carboxy-3-methoxymethylcyclopropyl) glycine (trans- and cis-MCG-I), effectively inhibited forskolin-stimulated cyclic AMP formation in a concentration dependent manner in cultured spinal neurones of rats. They effectively depressed monosynaptic excitation in the spinal reflex of newborn rats with IC50 values of 0.3 and 3 microM, respectively, which was sensitive to (+)-MCPG. They did not cause any depolarization even when the concentration was increased up to 0.3 mM. However, after treatment with quisqualate, cis-MCG-I caused a depolarization of motoneurones in the newborn rat spinal cord in a concentration dependent manner with a threshold concentration of 1 microM (quisqualate effect). The depolarizing activity developed after quisqualate treatment gradually decreased but lasted for more than 2 hr. The depolarization induced by cis-MCG-I seemed pharmacologically similar to that of phosphonate-containing analogues of glutamate such as L-AP4 or L-AP6 under the "quisqualate effect". These novel CCG derivatives would be expected to provide useful probes for elucidating the physiological function of mGluRs.

Animals↗
PubMed1995

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↗
PubMed1995

Trazodone treatment increases plasma prolactin concentrations in depressed patients.

m-Chlorophenylpiperazine (m-CPP), which is a metabolite of trazodone, is a serotonin agonist. To examine for the possibility that m-CPP is involved in biochemical effects during treatment with the parent compound, prolactin response to trazodone treatment (150 mg at bedtime for 3 weeks) was studied in 12 depressed patients. The means +/- S.D. of plasma prolactin concentrations before treatment, 12 h, and 1, 2 and 3 weeks after initiation of treatment were 9.1 +/- 5.6, 14.7 +/- 9.1, 15.3 +/- 8.5, 13.2 +/- 7.0 and 13.0 +/- 7.0 ng/ml, respectively. The mean prolactin concentrations at 12 h (p < 0.01), 1 week (p < 0.001) and 2 weeks (p < 0.05) were significantly higher than that before treatment. The present study thus shows that trazodone treatment increases prolactin concentrations, suggesting that m-CPP is involved in biochemical effects during treatment with the parent compound.

Adult↗
PubMed1995

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were studied in 43 depressed patients (19 males, 24 females) receiving trazodone 150 mg at bedtime for 1-3 weeks. Sixteen cases were smokers, and 19 cases were also receiving various benzodiazepines. The means (and ranges) of plasma concentrations of trazodone and mCPP, and the mCPP/trazodone ratio were 619 (251-1059) ng/ml, 59 (32-139) ng/ml and 0.100 (0.044-0.219), respectively. Smokers had significantly (p < 0.05) lower plasma concentrations of trazodone and higher mCPP/trazodone ratios than non-smokers. Age, sex and co-administration of benzodiazepines did not affect any plasma concentrations or the mCPP/trazodone ratio. In 11 cases where the dose was increased to 300 mg, neither plasma concentration/dose ratios nor the mCPP/trazodone ratio changed significantly. The present study thus suggests that: (1) there is a large Interindividual variation in the metabolism of trazodone; (2) smoking enhances the metabolism, but age, sex and co-administration of benzodiazepines do not affect it; (3) trazodone and mCPP have linear kinetics.

Adult↗
PubMed1995

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↗
PubMed1995

Genetic analysis of porcine H3N2 viruses originating in southern China.

From immunological and phylogenetic analyses of H3 influenza viruses isolated from pigs and ducks in the People's Republic of China (China), Hong Kong, Taiwan and Japan, between 1968 and 1982, we arrived at the following conclusions. The H3 haemagglutinin and N2 neuraminidase genes from swine isolates can be segregated into four mammalian lineages, including: (i) the earliest human strains; (ii) early swine strains including Hong Kong isolates from 1976-1977; (iii) an intermediate strain between the early swine and recent human strains; and (iv) recent human strains. In this study we found an unusual swine strain (sw/Hong Kong/127/82) belonging to the third lineage which behaved like those of the early swine-like lineage in the haemagglutination inhibition test; but neuraminidase inhibition profiles with monoclonal antibodies indicated that this virus is related to late human strains. On the basis of pairwise comparisons of complete or partial nucleotide sequences the genes encoding the three polymerase proteins (PB2, PB1, PA), the nucleoprotein, the membrane protein and possibly the nonstructural proteins of sw/Hong Kong/127/82 are of the swine H1N1 lineage, whereas genes encoding the two surface glycoproteins belong to the human H3N2 lineage. In contrast, all RNA segments of one swine isolate (sw/Hong Kong/81/78) are similar to those of recent human H3N2 viruses. This study indicated that frequent interspecies infections between human and swine hosts appeared to occur during 1976-82. Although the evolutionary rates of human (0.0122/site/year), swine (0.0127/site/year) and avian (0.0193/site/year) virus genes are similar when based upon synonymous substitutions, nonsynonymous substitutions indicated that viral genes derived from human and swine viruses evolved about three times faster (0.0026-0.0027/site/year) than those of avian viruses (0.0008/site/year). Furthermore, the evolutionary mechanism by which human and swine H3 haemagglutinin genes evolve at a similar rate, based on nonsynonymous substitutions, appeared to be quite different from previous evidence which showed that human H1 haemagglutinin genes evolved three times faster than those of swine viruses. However, comparison of the number of nonsynonymous substitutions in the antigenic sites (A-E) of haemagglutinin molecules demonstrated that swine viruses evolve at a rate that is about one fifth to one tenth that of human viruses, reflecting the conservative nature of the antigenic structure in the former.

Amino Acid Sequence↗
PubMed1995

Antigenic and genetic characteristics of H1N1 human influenza virus isolated from pigs in Japan.

Two strains of influenza A virus were isolated from pigs in northern Japan in 1992. Serological tests showed that the haemagglutinin (HA) and neuraminidase (NA) antigens were more closely related to those of recent human H1N1 viruses than to those of swine H1N1 viruses. The HA and NA genes of isolate A/sw/Obihiro/5/92 were shown to be closely related to those of current human H1N1 viruses. Evolutionary trees constructed from nucleotide sequences showed that the HA and NA genes of A/sw/Obihiro/5/92 were apparently on a branch cluster containing human strains isolated between 1990 and 1992.

Animals↗
PubMed1995

High-performance liquid chromatographic determination of trazodone and 1-m-chlorophenylpiperazine with ultraviolet and electrochemical detector.

A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m-CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C8 reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100-2000 ng mL-1 and for m-CPP in the concentration range 5-100 ng mL-1. The recoveries of trazodone and m-CPP added to plasma were 81.0-84.2 and 68.0-73.2%, respectively, with coefficients of variation of less than 7.3 and 8.2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone.

Chromatography, High Pressure Liquid↗
PubMed1995

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↗
PubMed1995

Angiotensin II activates pp60c-src in vascular smooth muscle cells.

The angiotensin II type-1 (AT1) receptor, a G protein-coupled receptor, lacks intrinsic kinase activity. However, recent data show that angiotensin II (Ang II) stimulates tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1), Stat91 (one of the signal transducers and activators of transcription), and paxillin in vascular smooth muscle cells. The tyrosine kinases responsible for these phosphorylation events are unknown. Src family kinases have been shown to phosphorylate PLC-gamma 1 and to be activated by G protein-coupled receptors. We hypothesized that pp60c-src associates with the AT1 receptor and is activated after Ang II stimulation of smooth muscle cells. We immunoprecipitated pp60c-src from Ang II-stimulated vascular smooth muscle cells and measured pp60c-src activity by autophosphorylation and by phosphorylation of enolase. Both assays demonstrated an approximately threefold increase in pp60c-src activity within 1 minute. A similar increase in Ang II-stimulated pp60c-src activity was observed in Chinese hamster ovary cells transfected with the AT1 receptor but not in untransfected cells. These data are the first to show that pp60c-src is activated by Ang II. To determine if pp60c-src associated with the AT1 receptor, the AT1 receptor was immunoprecipitated (with two different antibodies), and Western blots were performed with two different anti-pp60c-src antibodies. No pp60c-src was detected. In addition, direct interaction between the AT1 receptor and pp60c-src could not be demonstrated by using a glutathione S-transferase (GST)-AT1 fusion protein to bind proteins from cell lysates stimulated by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗