Search PubMed⌕ Search

Biomedical subjects

A Ishida

Publications and source records attributed to A Ishida.

At least 109 records · Page 6Linked to original sources

A novel protein phosphatase that dephosphorylates and regulates Ca2+/calmodulin-dependent protein kinase II.

A synthetic peptide corresponding to the autophosphorylation site of Ca2+/calmodulin-dependent protein kinase II (CaMKII) (residues 281-289) was conjugated to paramagnetic particles, and phosphorylated by a constitutively active CaMKII fragment. Using this phosphopeptide conjugate as a substrate, a calyculin A-insensitive, Mn(2+)-dependent, and poly-L-lysine-stimulated protein phosphatase activity was detected in the crude extract of rat brain. The protein phosphatase (designated as CaMKII phosphatase) (CaMKIIPase) was purified to near homogeneity from rat brain. CaMKIIPase showed apparent molecular weights of 54,000 and 65,000, on SDS-polyacrylamide gel electrophoresis and gel-filtration analysis, respectively. It was not inhibited by 100 nM calyculin A or 10 microM okadaic acid. Mn2+, but not Mg2+, was absolutely required for activity. CaMKIIPase was potently activated by polycations. Autophosphorylated CaMKII was dephosphorylated by CaMKIIPase, whereas phosphorylase kinase, mixed histones, myelin basic protein, and alpha-casein (which had been phosphorylated by cAMP-dependent protein kinase) and phosphorylase a (phosphorylated by phosphorylase kinase) were not significantly dephosphorylated. No other proteins than CaMKII in rat brain extract which had been phosphorylated by CaMKII were dephosphorylated. The stimulated Ca(2+)-independent activity of autophosphorylated CaMKII was reversed by the action of CaMKIIPase. Thus, CaMKIIPase appears to be a specialized protein phosphatase for the regulation of CaMKII.

Animals↗

Nitric oxide relaxes bovine ciliary muscle contracted by carbachol through elevation of cyclic GMP.

It is generally accepted that nitric oxide relaxes vascular smooth muscles by activating guanylyl cyclase, which in turn increases cyclic 3':5' guanosine monophosphate level. Despite the physiological significance of nitric oxide, very few studies have attempted to characterize the mode of action of this mediator in ciliary muscles. Therefore, the present experiments were designed to investigate whether or not the relaxation induced by sodium nitroprusside as a donor of nitric oxide is accompanied by the increase in cyclic 3':5' guanosine monophosphate level in the bovine ciliary muscle, and these responses are affected by methylene blue as an inhibitor of guanylyl cyclase and 3-isobutyl-1-methylxanthine as an inhibitor of phosphodiesterases. The relaxation activity of exogenous 8-bromo-cyclic 3':5' guanosine monophosphate was also determined. Sodium nitroprusside produced a concentration-dependent relaxation in the bovine ciliary muscle strips which had been contracted by carbachol as a cholinergic agonist. Relaxation in response to sodium nitroprusside was accompanied by a significant (P<0.05 and P<0.005) increase in cyclic 3':5' guanosine monophosphate level. The relaxation response and the increase in cyclic 3':5' guanosine monophosphate caused by sodium nitroprusside were significantly (P<0.01 and P<0.05) augmented by the pretreatment with 3-isobutyl-1-methylxanthine, and were significantly (P<0.005 and P<0.05) attenuated in the presence of methylene blue. The exogenously applied 8-bromo-cyclic 3':5' guanosine monophosphate relaxed the ciliary muscle strips in a concentration-dependent manner. These results suggest that nitric oxide causes relaxation of the bovine ciliary muscle through the activation of guanylyl cyclase and an increase in cyclic 3':5' guanosine monophosphate level.

1-Methyl-3-isobutylxanthine↗

[A case of ruptured descending thoracic aortic aneurysm due to Salmonella infection].

A 66-year-old male was admitted to our hospital because of pyrexia, chest pain and hemosptum. Inflammatory findings were made and salmonella enteritidis was detected by bacterial examination of sputum and stool. Enhanced chest CT examination disclosed a descending thoracic aortic aneurysm which had ruptured into the left lower lobe of the lung. Under a diagnosis of ruptured mycotic descending thoracic aortic aneurysm, an emergency operation was performed. A left posterolateral thoracotomy carried out after axillo-bilateral femoral bypass grafting. A pseudoaneurysm of the descending thoracic aorta had ruptured into the left lower lobe of the lung. After resection of the aneurysm, closure of both ends of the intact descending thoracic aorta and a left lower lobectomy were carried out. An ascending aorta-infrarenal abdominal aorta bypass was performed because of insufficient visceral arterial blood flow through the axillo-bilateral femoral bypass. The patient's immediate postoperative recovery was complicated by paraplegia. Chloramphenicol and levofloxacin were administered for three months, after which his recovery followed a good course.

Aged↗

Effect of N-methyl-D-aspartate and potassium on striatal monoamine metabolism in immature rat: an in vivo microdialysis study.

Effects of N-methyl-D-aspartate (NMDA) and potassium on 5-day-old rat's brain were examined. We measured extracellular striatal monoamines such as dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) using intracerebral microdialysis. After 3 h stabilization, pups received varying concentrations of NMDA (1-3 mM) and potassium (200-800 mM) by intrastriatal perfusion for 32 minutes. Increasing the concentration of NMDA and potassium induced a dose related DA increase (p < 0.001), whereas DOPAC, HVA, and 5-HIAA decreased significantly. Five days later the same animals were sacrificed and the weight reduction of their cerebral hemispheres was measured. The weight of the drug perfused side was significantly reduced compared with that of the contralateral one. We examined next the relationship between the level of maximum DA and the relative hemisphere weight reduction. The DA peak was highly correlated with the hemisphere weight reduction (r = 0.70, n = 52, p < 0.001 in the NMDA group, r = 0.83, n = 30, p < 0.001 in the potassium group, respectively). These data show that each treatment alter striatal monoamine metabolism in immature rat brain and that the extracellular DA peak is a potential early indicator to estimate brain injury.

3,4-Dihydroxyphenylacetic Acid↗

Trichomonas foetus meningoencephalitis after allogeneic peripheral blood stem cell transplantation.

A 34-year-old man with refractory acute myelogenous leukemia underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched sibling. Engraftment was prompt and no acute GVHD developed. However, high fever persisted even after engraftment, and the patient developed headache, diplopia, vertigo and nuchal rigidity on day 20 posttransplant. Cerebrospinal fluid (CSF) showed pleocytosis with no detectable microorganisms. Despite therapy with broad-spectrum antibiotics, antifungal agents and antituberculous drugs, he developed rapid mental deterioration with seizures and died on day 40. Just prior to his death, trichomonads were isolated from both CSF and urine. Scanning electron microscopic examination identified the trichomonad as Trichomonas foetus. At autopsy, trichomonads were detected histopathologically in an area involving meningoencephalitis. To our knowledge, this is the first case of T. foetus meningoencephalitis in a recipient of allogeneic PBSCT and, more importantly, the first human case of T. foetus infection.

Adult↗

Left ventricular mass regression after implantation of St. Jude Medical cardiac valves in small aortic roots.

In this study, we analyzed the extent of regression of left ventricular hypertrophy in patients who received small St. Jude Medical (SJM) aortic valves and compared the results with those of another group receiving larger valves. Eighty-eight patients received either 19 or 21 mm valves (Group 1, 25 patients) or either 23 or 25 mm valves (Group 2, 53 patients). Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). Doppler echocardiography derived pressure gradients for both groups were obtained during the follow-up period. As expected, the patients in Group 1 had higher peak pressure gradients than did those in Group 2. However, there was no significant difference between the 2 groups or any significant correlations between peak pressure gradients and body surface area (BSA). Actuarial survival was 84.7% at 15 years for Group 1 and 85.9% at 17 years for Group 2. Actuarial freedom from valve related events was 91.4% at 15 years for Group 1 and 82.7% at 17 years for Group 2. There was no significant difference in survival or valve related event free curves between the 2 groups. After implantations of SJM valves in small aortic roots, significant left ventricular mass regression was obtained, and the results were comparable to those for valves of other sizes. The long-term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients and survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.

Adult↗

Clinical factors influencing posttransfusion platelet increment in patients undergoing hematopoietic progenitor cell transplantation--a prospective analysis.

BACKGROUND: Platelet transfusion refractoriness remains problematic in the management of patients who have undergone hematopoietic progenitor cell transplantation. Bone marrow transplantation itself is reported to be a relevant factor hampering efficient platelet transfusions. However, a prospective analysis assessing factors affecting platelet transfusion efficacy in the setting of hematopoietic progenitor cell transplantation has yet to be conducted. STUDY DESIGN AND METHODS: To identify factors independently influencing platelet transfusion efficacy after hematopoietic progenitor cell transplantation, a prospective study was performed to determine the effectiveness of platelet transfusions by estimating posttransfusion (16-hour) corrected count increments (CCI) in 42 consecutive patients (26 who received allogeneic transplants and 16 who received autologous transplants) with 439 available platelet transfusions. RESULTS: The mean CCI and percentage of CCI <4500 for all transfusions were 6161.1 +/- 7775.2 per microL and 42.1 percent, respectively. Multiple linear regression analyses revealed high total bilirubin, total body irradiation, high serum tacrolimus, and high serum cyclosporin A to be major factors independently predicting a lower CCI. HLA antibodies with restricted specificity and platelet antibodies were detected transiently in 17 and 14 percent of the patients, respectively. The presence of these antibodies was not, however, associated with a poor response to platelet transfusions. CONCLUSION: Platelet transfusion efficacy in hematopoietic progenitor cell transplant recipients is markedly influenced by clinical factors specific to the procedure as well as those already recognized in other settings. Alloimmunization is not, however, a major factor associated with a poor response to platelet transfusions after this procedure.

Adolescent↗

EPR spectroscopic evidence for the mechanism-based inactivation of adenosylcobalamin-dependent diol dehydratase by coenzyme analogs.

EPR spectra were measured upon incubation of the complex of diol dehydratase with coenzyme analogs in the presence of 1,2-propanediol, a physiological substrate. When the analog in which the D-ribose moiety of the nucleotide loop was replaced by a trimethylene group was used as coenzyme, essentially the same EPR spectrum as that with adenosylcobalamin was obtained. The higher-field doublet and the lower-field broad signals derived from an organic radical and low-spin Co(II) of cob(II)alamin, respectively, were observed. With the imidazolyl counterpart, base-on cob(II)alamin-like species accumulated, but signals due to an organic radical quickly disappeared. When a coenzyme analog lacking the nucleotide moiety was incubated with apoenzyme in the presence of substrate, the EPR spectrum resembling cob(II)inamide was obtained, but no signals due to an organic radical were observed. From these results, it was concluded that the extinction of organic radical intermediates results in inactivation of the enzyme by these coenzyme analogs. Upon suicide inactivation with a [15N2]imidazolyl analog, the octet signals due to Co(II) showed superhyperfine splitting into doublets, indicating axial coordination of 5,6-dimethylbenzimidazole to the cobalamin bound to diol dehydratase.

Cobamides↗

Differential effect of nephrectomy on renal expressions of IGF-I and IGFBPs mRNA in selective growth hormone-deficient rats.

It is known that growth hormone (GH) contributes to glomerulosclerosis and that this probably occurs via insulin-like growth factor-I (IGF-I). However, the manner by which GH and nephrectomy (Nx) alter IGF-binding protein (IGFBP) mRNA in the kidney has not been fully explained. The effects of GH on renal IGF-I and IGFBP-1, 2, 3, 4, and 5 following Nx were examined in spontaneous dwarf rats (SDRs) which have a complete and specific lack of GH among pituitary hormones. In normal Sprague-Dawley rats (SDs), Nx resulted in significant decreases in levels of IGFBP-1 mRNA and IGFBP-5 mRNA to 62.7 +/- 4.9 and 56.5 +/- 5.0% those of sham-operated kidneys, respectively. Nx did not alter the IGF-I mRNA level in SDs. The levels of IGFBP-2, IGFBP-3, and IGFBP-4 mRNAs were likewise unchanged following nephrectomy. In SDRs, Nx significantly decreased the levels of IGFBP-1, IGFBP-4, and IGFBP-5 mRNA, to 57 +/- 2.6, 46 +/- 12, and 64 +/- 8.1% of sham-operated animals. However, Nx did not alter the levels of IGF-I, IGFBP-2, and IGFBP-3 mRNA. GH injections of nephrectomized SDRs fully normalized the decreased IGFBP-4 mRNA levels, whereas levels of IGFBP-1 and IGFBP-5 mRNA were not reversed. The altered expression of IGFBP-4 mRNA following Nx of SDRs compared to that of SDs appears highly significant since it is known that, unlike SDs, glomerulosclerosis does not fully develop in SDRs following renal ablation. The change in the IGFBP-4 mRNA level might be related to the development of glomerulosclerosis in SDs.

Animals↗

[Severe hepatic veno-occlusive disease (VOD) which was successfully treated with supportive therapy, but subsequently developed late-recurrence].

A 40-year-old man with chronic myelogenous leukemia in chronic phase received an allogeneic marrow graft from his HLA identical brother. He was conditioned with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). Graft-versus-host disease (GVHD) prophylaxis was attempted with cyclosporine A (CYA) and methotrexate. On day 30, weight gain, ascites and hepatomegaly developed in addition to an elevation of total bilirubin (TB). He was diagnosed as having veno-occlusive disease (VOD) and treated conservatively. The TB level increased up to 20.1 mg/dl on day 66, then reduced to 2.1 mg/dl on day 129. By that time ascites and hepatomegaly also had completely resolved. However, on day 134. The TB level started to increase again, when the lesions of chronic GVHD were observed in the eye, the mouth, and the skin. CYA was started on day 142, and FK506 was substituted for CYA on day 161. Despite the improvement of oral and skin lesions, TB level continued to rise, and he died of respiratory failure due to ARDS on day 186. Autopsy revealed both acute and old hepatic VOD lesions, suggesting the occurrence of late-onset VOD which probably contributed to the liver dysfunction observed after clinical resolution of the first episode of VOD.

Adult↗

[Long-term follow-up of patients with small St. Jude aortic valve prostheses].

Thirty-five patients received small sized 19 or 21 mm valves (group I) and 53 patients received 23 or 25 mm valves (group II). At follow-up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). The patients in group I had higher peak pressure gradients than did those in group II. However, there was no significant difference between the two groups, or any significant correlation between peak pressure gradients and body surface area. Actuarial survival was 84.7% at 15 years for group I and 85.9% at 17 years for group II. Actuarial freedom from valve-related events was 91.4% at 15 years for group I and 82.7% at 17 years for group II. There was no significant difference in survival or valve-related event free curves between the two groups. After implantation of small SIM valves, significant left ventricular mass regression was obtained and the results were comparable to those for valves of other sizes. The long-term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients, survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.

Aged↗

Short-term fasting alters neonatal rat striatal dopamine levels and serotonin metabolism: an in vivo microdialysis study.

Although frequent feeding is necessary for neonatal brains, rat pups were usually separated from their dams throughout a microdialysis experiment. First, in 5-day-old rats, we examined the effect of probe insertion on initial fluctuation of extracellular striatal monoamines using in vivo microdialysis and subsequent HPLC. Second, fasting effect on monoamine metabolism was examined with or without fasting; the latter was regarded as controls. Extracellular striatal DA in the fasting group decreased promptly to 60% of the basal level in the first 2 h, and reached 50% by the end of the experiment. Dopamine in the fasting group decreased more markedly than in the control group (P < 0.01 by ANOVA) which also decreased to about 80% of the basal level. Extracellular 5-hydroxyindole-3-acetic acid (5-HIAA) continuously increased (P < 0.01), and the serum concentration of tryptophan also increased in the fasting group (P < 0.001). We showed that extracellular striatal monoamine levels fluctuated especially in the first 2 h and fasting altered monoamine metabolism. Therefore, it should take at least 2 h after surgery to stabilize the animals and obtain adequate basal levels. In addition, we should consider that these alterations occur when we use fasting animals as controls in microdialysis studies.

Analysis of Variance↗

Secreted form of beta-amyloid precursor protein shifts the frequency dependency for induction of LTD, and enhances LTP in hippocampal slices.

The secreted form of beta-amyloid precursor protein (sAPP alpha) is released from neurons in an activity-dependent manner, and has been reported to modulate neuronal excitability in dissociated hippocampal neurons. We now report that sAPP alpha shifts the frequency dependence for induction of long-term depression of synaptic transmission (LTD) in hippocampal slices from adult rats. Whereas low frequency stimulation (1 Hz) of Schaffer collateral axons induced LTD of the post-synaptic response of CA1 neurons in control slices, it did not induce LTD in slices pretreated with sAPP alpha. On the other hand, whereas a 10 Hz stimulation normally induced neither LTD or LTP, it did induce LTD in slices pretreated with sAPP alpha. sAPP alpha potentiated LTP induced by high frequency stimulation. sAPP alpha induced cGMP production in hippocampal slices, and pretreatment of slices with 8-bromo-cyclic GMP mimicked the effect of sAPP alpha on LTD suggesting a role for cyclic GMP in modulation of LTD. The data suggest an important role for sAPP alpha in modulation of synaptic plasticity in the hippocampus.

Amyloid beta-Protein Precursor↗