Biomedical subjects

A Ishida

Publications and source records attributed to A Ishida.

At least 199 records · Page 11Linked to original sources

PubMed1994

Phosphorylation of Rabphilin-3A by calmodulin-dependent protein kinase II.

Rabphilin-3A is a putative target protein for Rab3A small GTP-binding protein which is implicated in neurotransmitter release. We have examined here whether Rabphilin-3A is phosphorylated by calmodulin-dependent protein kinase II (CaMKII). Recombinant Rabphilin-3A was phosphorylated by CaMKII purified from rat brain. Two moles of phosphate were maximally incorporated into one mole of Rabphilin-3A. The phosphorylation sites were Ser34, Thr205, Thr209, and Thr537. These results suggest that the CaMKII-catalyzed phosphorylation of Rabphilin-3A may modulate neurotransmitter release.

Adaptor Proteins, Signal Transducing↗

PubMed1994

An electrophysiological and immunohistochemical study of the hippocampus of the reeler mutant mouse.

The pyramidal cell layer in the CA1 subfield of the hippocampus of the reeler mouse is split into two laminae, the deep and the superficial. We examined the electrophysiological properties of double-layered CA1 pyramidal neurons in the reeler mouse hippocampal slice in vitro. We also studied cytoarchitectonic abnormalities in the hippocampus of this mutant by immunohistochemical methods using anti-parvalbumin and anti-F3/F11-protein antibodies. Laminar analysis of the postsynaptic field potentials in the CA1 subfield of the reeler hippocampus revealed broad negative field potentials with double negative peaks. In the CA1 subfield of the reeler mouse, tetanic stimulation of Schaffer collateral/commissural fibers induced long-term potentiation (LTP) in the majority of the deep layers (near alveus) examined, but very rarely in the superficial layer (near the molecular layer). Immunohistochemical study showed that parvalbumin-immunopositive neurons were densely concentrated in the hippocampus of the reeler mouse, especially in the stratum radiatum and the stratum lacunosum-molecular, in which only a few parvalbumin-immunoreactive neurons were seen in the normal mouse. Abnormal trajectories of axons arising from malpositioned pyramidal cells in the CA1 subfield of the reeler mouse were identified by F3/F11 immunohistochemistry. Interestingly, F3/F11-immunoreactive Schaffer collaterals were misdirected in the CA1 subfield of this mutant. The present electrophysiological and immunohistochemical data suggest that impairment of LTP in the superficial layer of the CA1 pyramidal neurons appears to be mainly due to strong inhibitory inputs to this malpositioned population of neurons.

Animals↗

PubMed1994

Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma.

BACKGROUND: Several uncontrolled trials have suggested that dose intensity of chemotherapy is a crucial determinant of treatment outcome for patients with non-Hodgkin's lymphoma (NHL). To explore the possibility of increasing dose intensity, a dose-escalation study of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) using recombinant human granulocyte colony stimulating factor (rhG-CSF) was initiated. METHODS: First, the feasibility of standard dose CHOP (750 mg/m2 cyclophosphamide intravenously [i.v.] on Day 1;50 mg/m2 doxorubicin i.v. on Day 1; 1.4 mg/m2 vincristine i.v. on Day 1; and 100 mg/body prednisolone orally on Days 1-5) repeated biweekly at the original dose was assessed. rhG-CSF was given subcutaneously at doses of 2-5 micrograms/kg every day or every other day on Days 3-13. The safety of increasing the dose of cyclophosphamide during biweekly CHOP then was tested. Besides the standard dose (750 mg/m2), two dose levels of cyclophosphamide were set (1200 mg/m2 and 1500 mg/m2 in patients younger than 61 years of age, and 1200 mg/m2 in patients 61-75 years old). RESULTS: Twenty-seven patients with NHL who had received minimal or no previous treatment were enrolled in this study. In the 750 mg/m2 group, 9 patients received 3-6 cycles of treatment (mean, 3.9 cycles), in the 1200 mg/m2 group, 10 patients received 3-6 cycles (mean, 4.8), and in the 1500 mg/m2 group, all 8 patients received 6 cycles. No significant differences among the groups were observed in the extent and the duration of neutropenia in each cycle, and a leukocyte count of more than 3000/microliters on Day 15 was achieved in all 131 cycles. Hemoglobin values and platelet counts, however, decreased in the later cycles in the 1500 mg/m2 group. Two patients were hepatitis-B virus carriers, one of whom died of fulminant hepatitis after completion of six cycles. Another patient developed a transient increase of transaminases after the second cycle. One other patient developed Grade 4 mucositis (World Health Organization scale). The numbers of patients who achieved complete and partial responses, respectively, were 4 (50%) and 2 (25%) in the 750 mg/m2 group, 8 (80%) and 2 (20%) in the 1200 mg/m2 group, and 8 (100%) and 0 (0%) in the 1500 mg/m2 group. CONCLUSIONS: The dose of cyclophosphamide in biweekly CHOP can be increased up to 1500 mg/m2 with no increase in the incidence of treatment-related early mortalities without any organ damage in younger patients. The efficacy of this dose intensification of CHOP currently is being investigated in a multicenter prospective randomized trial using three different dose levels of cyclophosphamide.

Adult↗

PubMed1994

Changes in IP3 3-kinase immunoreactivity following transient ischaemia in gerbil hippocampus.

The distribution of inositol 1,4,5-triphosphate 3-kinase (IP3 3-kinase) in the gerbil hippocampus was studied before and after transient ischaemia, by immunohistochemistry and immunoblot with monoclonal antibody to IP3 3-kinase. In control gerbils, intense IP3 3-kinase immunoreactivity was localized in the dendritic field of CA1 pyramidal neurones. However, after ischaemia for 5 min, the immunoreactivity decreased gradually, until after 24 h there was very little IP3 3-kinase detectable. Immunoblot study showed a similar decrease of IP3 3-kinase in ischaemic hippocampus. Infliction of 2 min ischaemia prior to the 5 min of ischaemia is known to have a protective effect on the 5 min ischaemia. With the addition of the 2 min ischaemia there was no decrease in IP3 3-kinase following the 5 min ischaemia. The results suggest that IP3 3-kinase might play a critical role in inducing the delayed neuronal death following ischaemia.

Animals↗

PubMed1994

The effect of 6 kHz tone exposure on inner ear function of the guinea pig: relation to changes in cochlear microphonics, action potential, endocochlear potential and chemical potentials of K(+)-ions and Na(+)-ions, using a double-barrel glass electrode.

Using 97 male albino guinea pigs and applying electrophysiological methods, the effects of a 6 kHz tone were investigated at a moderate sound pressure level to the inner ear during a 24-h exposure time. Following exposure to the 6 kHz tone at 90 dB, cochleas showed decreased maximum output voltage of cochlear microphonics (CM) and action potential (AP). In the endolymph, K+ ion and Na+ ion concentrations remained unchanged during 40 min anoxia and 90 dB tone exposure. At 80 dB sound exposure decreases in maximum output voltage of CM and AP and decreases in the absolute value of EP could not be detected. Endolymph K(+)-ion Na(+)-ion concentrations were also unchanged. These findings indicate that diffusion potentials are induced at the same time as decreases of maximum output voltage in CM induced by exposure to sound at 90 dB.

Action Potentials↗

PubMed1994

Microbiological activities of nucleotide loop-modified analogues of vitamin B12.

Novel vitamin B12 analogues in which the D-ribose moiety of the nucleotide loop was replaced by an oligomethylene group and a trimethylene analogue containing imidazole instead of 5,6-dimethylbenzimidazole as well as cobinamide methyl phosphate were tested for biological activities with Escherichia coli 215, a B12- or methionine-auxotroph, and Lactobacillus leichmannii ATCC 7830 as test organisms. A cyano form of 5,6-dimethylbenzimidazolyl tetramethylene, trimethylene and hexamethylene analogues supported the growth of L. leichmannii in this order. 5,6-Dimethylbenzimidazolyl dimethylene and imidazolyl trimethylene analogues did not show B12 activity and behaved as weak B12 antagonists when added together with cyanocobalamin. An adenosyl form of the biologically active analogues served as coenzymes for ribonucleotide reductase of this bacterium, whereas that of the inactive analogues did not. The latter acted as weak competitive inhibitors against adenosylcobalamin. On the contrary, all the analogues did not support the growth of E. coli 215 at all by themselves and inhibited the growth when added with a suboptimum level of cyanocobalamin. A methyl form of the analogues also did not support the growth of E. coli 215, although they served as active coenzymes for methionine synthase of the bacterium. Since unlabeled analogues strongly inhibited the uptake of [3H]cyanocobalamin by this bacterium, it seems likely that the analogues exert their anti-B12 activity toward E. coli 215 by blocking the B12-transport system.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed1994

Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the gerbil hippocampus.

We studied the expression of bcl-2 oncoprotein in the gerbil hippocampus after transient ischemia. Immunostaining using monoclonal antibody raised against bcl-2 oncoprotein revealed intense immunoreactivity in the CA1 area following 2 min of ischemia, which induced tolerance to subsequent ischemia and prevented delayed neuronal death (DND). Following ischemia for 5 min, however, bcl-2 oncoprotein immunoreactivity was decreased, reflecting neuronal death in the CA1 area. However, pretreatment with ischemia of 2 min that prevented DND due to subsequent ischemia for 5 min, showed increased immunoreactivity. On the other hand, following 1 min of ischemia which failed to induce tolerance, no increase in the bcl-2 oncoprotein was observed. The results evidenced that expression of bcl-2 oncoprotein in the CA1 area following brief ischemia is closely related to the acquisition of resistance to DND.

Animals↗

PubMed1994

Inactivation of Ca2+/calmodulin-dependent protein kinase II by Ca2+/calmodulin.

Incubation of calmodulin-dependent protein kinase II with Ca2+ and calmodulin resulted in a marked inactivation of the enzyme. Chelation of Ca2+ by EGTA or addition of calmodulin antagonists, W-7 or trifluoperazine, completely blocked this inactivation. The concentration required for the half-maximal inactivation, 127 microM, is three to four orders of magnitude higher than that for the half-maximal activation of the enzyme. The Ca2+/calmodulin-independent activity of the proteolytic fragment of the enzyme, whose calmodulin-binding site involved in the enzyme activation was deleted, was also decreased by incubation with Ca2+ and calmodulin. These results suggest that calmodulin-dependent protein kinase II possesses a second, low-affinity calmodulin-binding site, which is distinct from the calmodulin-binding site involved in the activation of the enzyme, and that the binding of calmodulin to the second binding site causes the inactivation of the enzyme. The inactivation by Ca2+/calmodulin was temperature-dependent. The addition of both 500 microM ADP and 10 mM MgCl2 markedly protected the enzyme against the inactivation, while such a marked protection was not observed after the addition of either of the two alone. The addition of 5 microM autocamtide-2, a synthetic substrate peptide containing the amino acid sequence of the autophosphorylation site (Thr286/Thr287 in alpha/beta, gamma, and delta isoforms) lying within the autoinhibitory domain, also protected the enzyme against the inactivation by Ca2+/calmodulin, while syntide-2, another synthetic substrate peptide corresponding to a phosphorylation site of glycogen synthase, did not protect it even at a concentration as high as 304 microM.

Animals↗

PubMed1994

Left ventricular preload reserve in preterm infants with patent ductus arteriosus.

The left ventricular Frank-Starling response was studied in 15 preterm infants, less than 1500 g birth weight, and in 16 fullterm infants with patent ductus arteriosus. Left ventricular end diastolic volume (LVEDV), stroke volume, and cardiac output were calculated from biplane echocardiographic images with a modified Simpson's rule, and the left ventricular function curve was obtained by standardising with birth weight and body length. In the relationship between LVEDV and stroke volume, the slope of the regression line was significantly milder in preterm than in fullterm infants; however, there was no significant difference in the relationship between LVEDV and cardiac output. The heart rate was significantly higher in preterm than in fullterm infants. Our data indicated that the premature infants had less left ventricular reserve capacity to respond to the increased preload through the left-to-right ductal shunting than the mature ones, and that the high pulse rate made it possible to generate adequate cardiac output in premature infants.

Cardiac Output↗

PubMed1994

Neurons with high-frequency discharge in the central nervous system in chronic pain.

Prior to implantation of the thalamic- or motor cortex-stimulating electrodes for relieving chronic pain, extracellular unitary activity was recorded and local microstimulation was done, by using microelectrodes, mainly in the ventral caudal nucleus of the thalamus. A significant number of high frequency discharge neurons (hyperactive neurons) were recorded and showed three types of discharge patterns with different interval histograms. In animal experiments, unilateral dorsal root sectioning from C5 to Th1 of male Wistar rats was made according to the method of Lombard et al[4]. One to three months after the operation, cellular activity was recorded from the contralateral thalamic nuclei (VP, zona incerta), lemniscus medialis and striatum. Hyperactive neurons were recorded from the thalamic nuclei and lemniscus medialis. The firing patterns and distribution of hyperactive neurons in these animals were very similar to those of humans. Hyperactive neurons were examined via electrical stimulation of and/or iontophoretical application of chemical substances. Hyperactive neurons were unaffected by electrical stimulation of the nucleus raphe dorsalis and locus ceruleus. However, sensorimotor cortical stimulation showed a reduction of firing in the hyperactive neurons. Iontophoretic application of glutamate showed increase in firing and GABA showed remarkable firing suppression. These results suggested that hyperactive neurons of the thalamic nuclei receive a facilitatory effect from the sensorimotor cortex with little influence from adrenergic or serotonergic systems, and these neurons have a relationship to the glutamatergic and GABAergic fibers or receptors.

Action Potentials↗

PubMed1994

Left ventricular contractile state of early human neonates with patent ductus arteriosus.

Using echocardiographic technique, we studied the left ventricular (LV) contractile state in 32 full-term infants within 24 hr after birth. They were divided into 2 groups based on the timing of the examinations; the group 1 (n = 17), < 3 hr after birth; the group 2 (n = 15), > 3 and < 24 hr after birth, and the additional examinations were performed on day 5. The patency of the ductus arteriosus and its internal diameter were determined by pulsed Doppler and two-dimensional echocardiography. The left atrial to aortic root ratio was obtained from M-mode echocardiography, and the LV contractile state was estimated by the relationship between heart rate-corrected velocity of circumferential fiber shortening (mVcfc) and end-systolic meridional wall stress (ESS). The ductus arteriosus was open in all cases of group 1 and in 83% of the cases of group 2, but the ductal diameter and the left atrial to aortic root ratio significantly decreased in group 2. The relationship between mVcfc and ESS showed no significant differences between 2 groups and the control. Afterload, represented as ESS, was significantly lower in group 1 than the control. We suggest that the low afterload condition helps the adequate LV contraction even under the increased preload through the left-to-right ductus arteriosus shunting after birth.

Blood Flow Velocity↗

PubMed1994

A preterm infant with secondary carnitine deficiency due to MCT formula--effective treatment of L-carnitine.

We report a preterm infant who was prescribed an MCT formula and subsequently developed carnitine deficiency with liver dysfunction and an elevation of serum CK level. A male infant who had been born at 24 weeks' gestation with birth weight 799 g, was fed with an MCT formula containing 76.8% of all kinds of lipids, because of his steatorrhea after the 30th day. On the 100th day, he was noted hepatomegaly and elevation of serum levels of AST, ALT and CK. The needle biopsy of the liver indicated the existence of the liver damage. He showed low serum carnitine with high urinary loss of acylcarnitine and dicarboxylic aciduria. Administration of L-carnitine was an effective treatment. The carnitine deficiency might be exaggerated by an increased urinary loss of acylcarnitine. We should be cautious of the risk of carnitine deficiency in preterm infants during prolonged use of MCT formula.

Carnitine↗

PubMed1994

Psychiatric evaluation of rehabilitation patients.

Patients undergoing physical rehabilitation have experienced a severe object loss and it is suggested that many patients in rehabilitation might have psychiatric disorders. We conducted a study to demonstrate the frequency and kinds of psychiatric and psychological symptoms. A Structured Interview according to the DSM-III-R was conducted, which demonstrated that 27 (43.5%) out of 62 rehabilitation inpatients met the criteria for some form of psychiatric disorders; 22 patients for major depression and five for adjustment disorder with anxious mood. The remaining 35 patients (56.5%) showed normal reactions to their diseases. They were also administered Zung's Self-rating Anxiety Scale (SAS), Zung's Self-rating Depression Scale (SDS) and Profile of Mood States (POMS). These three psychological tests were useful in detecting depression or adjustment disorder among rehabilitation patients; but they were not always specific to the type of psychiatric disorders. Patients with higher scores in these inventories should be referred to a psychiatric consultant for detailed examinations and proper treatment if necessary.

Adjustment Disorders↗

PubMed1994

[Effects of Chinese medicine on bovine ciliary muscles].

We studied the effects and characteristics of Chinese medicines (Gorei-san (I), Saiko-keishi-to (II), Ryokei-jutsu-kan-to (III), Shokenchu-to (IV)), on the contractions (A) of bovine ciliary muscles. Ciliary muscle strips (width 4 mm x length 6 mm) were prepared and were contracted by a cholinergic agent, carbachol (10(-5)M). The 4 Chinese medicines were diluted to the concentrations of 10(-3)-10(-6) of each adult dosage per day. When these diluted medicines were added, all caused relaxations in a concentration-dependent manner. The percentages of (max B/max A) x 100 were: Gorei-san, 41 +/- 14 (%) (n = 6, mean +/- SD); Saiko-keishi-to, 37 +/- 18% (n = 6); Ryokei-jutsukan-to, 26 +/- 16% (n = 6); and Shokenchu-to, 10 +/- 5% (n = 6). Compared to the control group which did not receive Chinese medicines, drugs I, II and III showed statistically significant relaxation effects (p < 0.05). The amount of relaxation caused by these medicines (I-III) was 1/3-1/4 of the relaxation caused by a cholinergic antagonist, cyclopentlate (10(-5)M). The results suggest that Chinese medicines (I-III) produce moderate relaxation of ciliary muscles.

Animals↗

PubMed1994

[Characteristics of contraction force of bovine ciliary muscles caused by cholinergic agent].

We studied the contractions caused by the cholinergic agent carbachol on bovine ciliary muscles. Ciliary muscle strips (width 4 mm x length 6 mm) were prepared in the directions of the longitudinal and circular muscles. Contractions were measured with an isometric tension recorder. The concentration for 50% effective dose was 10(-7) M carbachol, and maximum contraction was obtained at 3 x 10(-6) M. Also, maximum contraction was obtained at a resting tension of 600 mg for the longitudinal direction and 400 mg for the circular direction. At a resting tension of 400 mg and concentration of 10(-5) M, average contraction for the longitudinal direction (L) was 335 +/- 106 mg (mean +/- SD, n = 20) and 104 +/- 52 mg (mean +/- SD, n = 20) for the circular direction (C). The ratio between L and C was about 3:1. The results suggest that bovine ciliary muscles have more ability to perform accommodation than in previous reports, and that the magnitude of contractions depends on the direction of the ciliary muscle fibers.

Animals↗

PubMed1994

[Mechanical characteristics of the bovine choroid].

We studied the mechanical relationship between the tension and the length of stretch of bovine choroids. Longitudinal and circular choroidal strips (4 mm x 6 mm) were prepared at 3 different locations (I. ora serrata, II. anterior to the equator, III. posterior to the equator). Using a force transducer and a potentiometer, changes in the tension and the length of stretch were recorded simultaneously. At a tension of 600 mg, longitudinal strips stretched more than circular strips at all 3 locations (p < 0.05). Longitudinal strips all stretched to almost the same length (about 1.3 mm), but circular strips stretched less in the order of I, II and III. These results suggest that there are mechanical characteristics in the bovine choroid allowing it to stretch more in the longitudinal direction than in the circular direction.

Animals↗

PubMed1994

Hemolytic uremic syndrome without hemolytic anemia: a case report.

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Most cases of HUS are caused by E. coli O157:H7 verotoxin. In the case reported here, diarrhea continued for twenty days after an E. coli 0157:H7 infection and was followed by acute renal failure and thrombocytopenia. Examination of percutaneous renal biopsy tissue showed typical HUS findings, e.g., mesangiolysis in glomeruli and thickening of capillary walls with prominent double outlines, but there was no indication of hemolytic anemia. LDH and haptoglobin, indications of hemolytic anemia, were in the normal range throughout the patient's clinical course. The patient's red blood cells had P1 antigen, which reportedly provides protection by adsorption of toxin into the red blood cells thereby preventing or limiting toxic damage to other organs. Therefore, we assumed that because of the expression of P1 antigen in this patient, the kidneys were not severely damaged and microangiopathic hemolytic anemia was thereby avoided.

Acute Kidney Injury↗

PubMed1994

[Reoperation after open mitral commissurotomy for mitral stenosis].

Between 1975 and 1993, 16 of 95 patients who received open mitral commissurotomy for mitral stenosis required reoperation for recurrent mitral lesions with a mean duration of 11 years after the initial operation at Kawasaki Medical School Hospital. The mitral lesions necessitating reoperation involved restenosis in eight, stenoinsufficiency in six and regurgitation in two. In 13 patients, mitral commissure was well separated, and the mitral restenosis and regurgitation were caused by progressions of valvular and subvalvular lesions. Significant tricuspid valve regurgitation was also seen in nine patients, and in seven out of eight patients who were in NYHA functional class III or IV, tricuspid regurgitation of grade 3 was observed. The combined tricuspid regurgitation aggravated the patient's symptoms and became a major risk factor of the reoperation after open mitral commissurotomy.

Catheterization↗