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Biomedical subjects

K Ikeda

Publications and source records attributed to K Ikeda.

At least 19 recordsLinked to original sources
PubMed1992

Coexistence of paired helical filaments and glial filaments in astrocytic processes within ghost tangles.

Ultrastructural examination of ghost tangles in an autopsy case of long-term Alzheimer's disease revealed, in addition to degenerate neurites containing paired helical filaments (PHF), astrocytic processes which included PHF. This finding suggests either that astrocytes in ghost tangles possess the capacity to produce PHF or that PHF are incorporated into astrocytes by endocytosis.

Actin Cytoskeleton↗
PubMed1992

Increased plasma concentrations of aspartate, glutamate and glycine in Parkinson's disease.

We measured fasting plasma amino acids in 20 patients with Parkinson's disease (PD) and 20 controls matched for age and sex. PD patients had significant elevations in plasma levels of aspartate, glutamate and glycine. The levels of other amino acids were not significantly different from those found in controls. No correlation was noted between PD severity and the degree of abnormality of plasma amino acids. We conclude that excitatory amino acids may be altered in patients with PD, and raise the possibility that neuroexcitotoxic mechanisms may be involved in the neurodegeneration of PD.

Aged↗
PubMed1992

The T-loop region of animal mitochondrial tRNA(Ser)(AGY) is a main recognition site for homologous seryl-tRNA synthetase.

Recognition sites of bovine mitochondrial serine tRNA specific for condons AGY [tRNA(Ser) (AGY)] by the cognate mitochondrial seryl-tRNA synthetase were studied using a range of tRNA(Ser)(AGY) variants which were obtained by the in vitro transcription of synthetic tRNA genes with T7 RNA polymerase. Base replacements in the anticodon and discriminator sites did not affect serine acceptance. However, deletion and/or replacement in the T-loop region completely deprived the variants of their charging activities. Point mutation experiments in this region also showed that the adenosine residue in the middle of the T-loop (position 58), which is involved in tertiary interaction between the T-loop and the truncated D-arm [de Bruijn and Klug, 1983] played a significant role in the recognition process by the synthetase.

Animals↗
PubMed1992

[Liver abscess formation after treatment of liver cancer by arterial injection using adriamycin/mitomycin C oil suspension (ADMOS)].

Of 210 patients with hepatocellular carcinoma (n = 135), metastatic liver cancer (n = 71) and cholangiocarcinoma (n = 4) who underwent intra-arterial infusion of adriamycin and/or mitomycin C oil suspension (ADMOS) and cisplatin, and both regimens, pyogenic liver abscess occurred in seven (3.3%). The percentages of abscess formation in the respective types of liver cancer were 0.8, 7.0 and 25%. These differences among the three types of liver cancer were attributed to the volume of the tumor vascular beds to be embolized, which might determine the relative amount or regional Lipiodol retention in the tumor and normal liver tissue. Four of seven patients with hepatic abscess had received the intra-arterial infusion of ADMOS, and their angiographic findings showed sequential decreases in the vascular beds of the tumor in comparison with those of previous infusion procedures; all had hypovascular liver tumors angiographically. We have never experienced this complication in other treatments such as embolization of the hepatic arteries and intra-arterial infusion of water-soluble anticancer drugs alone. These results suggest that the most important factor leading to abscess formation is the ischemic destruction of the intrahepatic ducts secondary to occlusion of the peribiliary arterial plexus by Lipiodol and/or the direct effects of anticancer drugs on these vessels. To avoid this complication, the volume of Lipiodol used for intraarterial infusion therapy should be carefully determined, especially when the patient has hypovascular tumors of the liver and a history of multiple previous intraarterial infusion procedures of anticancer drug. The use of ADMOS should be avoided in patients with hypovascular tumors of the liver such as secondary deposits and cholangiocarcinoma.

Adenoma, Bile Duct↗
PubMed1992

Apolipoprotein B immunoreactivity in senile plaque and vascular amyloids and neurofibrillary tangles in the brains of patients with Alzheimer's disease.

Based upon our previous finding of the association of apolipoprotein E (apoE) immunoreactivity with cerebral amyloids and neurofibrillary tangles (NFTs), we examined immunohistochemically whether this is also the case for apolipoprotein B (apoB). Polyclonal antibody to apoB immunosustained senile plaque amyloid, vascular amyloid, subpial amyloid deposits and intracellular NFTs in formalin-fixed, paraffin-embedded brain sections from patients with Alzheimer disease. Hydrated autoclave pretreatment of the sections enhanced the staining of plaque amyloid. The results may suggest a role of apoB in amyloid and NFT formation.

Aged↗
PubMed1992

Evidence that neurofibrillary tangles undergo glial modification.

Ghost tangles, neurofibrillary tangles (NFTs) emerging into extracellular space, appear to be subjected to some microglial association in addition to an invasion of astrocytic processes. Our findings lead us to speculate that the NFTs undergo structural and immunocytochemical modification. Electron microscopic observation of the NFTs in the vascular region indicated either the discharge of NFTs into the vessel or formation of NFTs in the astrocytic end-foot.

Aged↗
PubMed1992

Comparison of the anticancer effect of ADMOS alone and ADMOS with CDDP in the treatment of hepatocellular carcinoma by intra-arterial injection.

A total of 135 patients with hepatocellular carcinoma (HCC) were treated by intra-arterial injection of an Adriamycin/mitomycin C oil (lipiodol) suspension (ADMOS) alone or of ADMOS plus cis-diammine-dichloroplatinum (CDDP). In all, 59 patients were treated with ADMOS alone and 76 were treated with ADMOS plus CDDP. A reduction of more than 25% in the tumor size was obtained in 13 of 38 (34%) evaluable patients in the former group and in 39 of 76 (51%) evaluable patients in the latter group. Serum alpha-fetoprotein (AFP) levels decreased by more than 50% in 10 of 17 (59%) and 23 of 33 (70%) patients in the respective groups whose pretreatment AFP level was estimated to be over 200 ng/ml. Overall, the 1-year survival value was 68% and the 2-year value was 41% as determined by the Kaplan-Meier method. No statistically significant difference in survival was observed between the two groups. The initial tumor response correlated with the survival value. No severe complication was encountered except for one case of liver abscess formation. No serious change in the laboratory data was observed following treatment with these regimens. Although the tumor response was significantly better in patients treated with ADMOS combined with CDDP injection than in those treated with ADMOS alone (P < 0.05), no significant difference in survival was found between the two groups.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Alanine aminotransferase and HCV-RNA responses following interferon therapy of HCV-RNA positive chronic hepatitis.

Interferon (IFN) has been shown to be effective for chronic hepatitis C. This study investigated changes of alanine aminotransferase (ALT) and HCV-RNA in chronic hepatitis C patients treated with alpha-IFN. IFN was given to 73 patients with HCV-RNA positive chronic hepatitis C. The pattern of changes in ALT activity after IFN administration was classified into five types. Type 1 was characterized by normalization of ALT (< or = 25 K.U) during IFN administration and sustained normalization after the IFN therapy. Type 2 involved a rebound of ALT after termination of IFN therapy and subsequent normalization. Type 3 had no ALT normalization during IFN administration, with normalization after the completion of the therapy. Type 4 involved transient normalization of ALT level during IFN therapy, with a subsequent reversion to abnormal levels after the termination of IFN therapy. Type 5 showed sustained abnormally high levels of ALT activity both during and after treatment. Twenty four patients (32.9%) had sustained normalization ALT (< or = 25 K.U) after the termination of IFN treatment. The HCV-RNA negative rate at 6 months after IFN therapy in patients with sustained normalization of ALT was 87.5% (21/24).

Adult↗
PubMed1992

Postoperative central conduction time and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage: relationship with prognosis and ischemic conditions.

Cerebral blood flow (CBF) and somatosensory evoked potential (SEP) were monitored periodically on 32 patients who underwent aneurysm clipping within 3 days after subarachnoid hemorrhage (SAH). From the SEP data, central conduction time (CCT) was obtained, and CCT fluctuations were categorized into three types. Patients with CCT prolongation over 7.5 ms within 10 days after SAH tended to have poor recovery of CBF and unfavorable outcome. Therefore, periodical monitoring of CCT was considered as a useful indicator for predicting prognosis and post-SAH changes of cerebral blood flow.

Adult↗
PubMed1992

Paraquat damage of rat liver mitochondria by superoxide production depends on extramitochondrial NADH.

Pure rat liver heavy mitochondrial fractions, in which the absence of significant microsomal contamination was confirmed by electron microscopy and by the lack of glucose-6-phosphatase activity, were used to demonstrate the effect of paraquat on mitochondrial ultrastructure in the presence of external NADH. Starved mitochondria (orthodox conformation) did not show O2 uptake or structural injury from either paraquat alone or NADH alone. Marked O2 uptake and structural breakage occurred only when paraquat and NADH were added in combination. These alterations were resistant to rotenone and malate plus glutamate or NADPH could not substitute for NADH. Paraquat was reduced anaerobically by the mitochondria in the presence of NADH, but not of NADPH. The addition of superoxide dismutase, ferricytochrome c or p-benzoquinone protected against the breakage of mitochondria caused by paraquat plus NADH. These results demonstrate that mitochondria may produce paraquat radicals in the presence of extramitochondrial NADH and thus generate superoxide anion radicals, resulting in structural injury to the mitochondria, by mechanisms that may involve the mitochondrial outer membrane rather than the electron transfer chain. These mitochondrial mechanisms in paraquat toxicity seemed to be more probable in vivo than are microsomal mechanisms; the latter are postulated to function in detoxication because phenobarbital diminished paraquat toxicity and SKF 525-A or cobaltous ions enhanced the toxicity.

Animals↗
PubMed1992

Intracellular pH regulation in isolated cochlear outer hair cells of the guinea-pig.

1. The intracellular pH (pHi) regulation mechanisms of the outer hair cell (OHC) isolated from the guinea-pig were studied using fluorescence ratio imaging microscopy. 2. The OHC pHi in the resting condition was 7.26 +/- 0.08 (mean +/- S.D., n = 49) when the standard solution buffered with HEPES-Tris was superfused. 3. Exposure to 25 mM-NH4+ in the absence of HCO3- caused biphasic changes in pHi; a transient increase (7.89 +/- 0.14, n = 22) followed by a slow decrease (7.57 +/- 0.12; mean +/- S.D.). Removal of external NH4+ by introducing the N-methyl-D-glucamine (NMDG+) solution in the absence of HCO3- markedly acidified the pHi to 6.38 +/- 0.12 with little pHi recovery. Subsequent application of the standard Na+ solution restored the pHi to the initial value. The recovery was inhibited by 0.5 mM-amiloride but not by 0.3 mM-DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid). 4. In the presence of HCO3-, removal of both external NH4+ and Na+ promptly caused an intracellular acidification followed by a pHi recovery. The pHi recovery from an acid load was inhibited by 0.3 mM-DIDS or 10 microM-NPPB (5-nitro-2-(3-phenylpropyl-amino)-benzoate). However, the pHi in the steady state in the presence or absence of HCO3- was not altered by addition of 0.5 mM-amiloride or NMDG+ solution. 5. The intracellular buffering power obtained from the NH4+ exposure and withdrawal was -15.1 +/- 8.7 mM (pH unit)-1 (n = 6) and -14.3 +/- 5.8 mM (pH unit)-1, respectively. 6. Replacement of external Cl- with gluconate in the HCO3- solution increased the pHi from 7.22 +/- 0.12 to 7.51 +/- 0.20 (n = 6), which was inhibited by 0.3 mM-DIDS. Moreover, addition of DIDS to the HCO3- solution increased the pHi by 0.13 +/- 0.08 (n = 8). 7. When the external standard solution buffered with HEPES-Tris was replaced with the HCO3- solution, the basal pHi (7.27 +/- 0.10) was promptly acidified to 6.87 +/- 0.10 then relaxed slowly to 7.00 +/- 0.15 (n = 16). 8. The pHi showed an initial alkalinization and a subsequent slow acidification after the HCO3(-)-free standard solution replaced the HCO3- solution. The slow acidification was inhibited by low external Cl- concentration or by addition of 0.3 mM-DIDS.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetazolamide↗
PubMed1992

Neurogenic bladder due to peripheral neuropathy and a visual disturbance in an elderly man with systemic lupus erythematosus.

A 63 year old man with central nervous system lupus with a neurogenic bladder and visual disturbance is described. The diagnosis of neurogenic bladder, attributed to peripheral neuropathy, was made on the basis of cystometrography and clinical symptoms. A brain magnetic resonance imaging scan showed gliosis along the cerebral vessels and the optic nerve. This case shows that systemic lupus erythematosus can be accompanied by a peripheral neurogenic bladder and visual disturbance, and that these symptoms may not improve despite the amelioration of other lupus symptoms on treatment with steroids.

Follow-Up Studies↗
PubMed1992

Transforming growth factor-beta modulates receptor binding of calciotropic hormones and G protein-mediated adenylate cyclase responses in osteoblast-like cells.

Transforming growth factor-beta (TGF beta) produced by osteoblasts is present in high levels in bone and influences bone formation, replication of bone cells, and expression of osteoblast protein products. Interactions between bone active hormones and locally released and activated TGF beta were studied by examining the influence of TGF beta preincubation on PTH, calcitonin (CT), and vitamin D receptors in an osteoblastic cell line (UMR 106-06). Preincubation of UMR 106-06 cells with 1 ng/ml TGF beta for 3 days increased specific binding of [125I]PTH-related protein (PTHrP)(1-84) to 140% of that in control cells, but [125I]salmon CT binding decreased to 50% of controls. Binding isotherms indicated that the changes in binding were due to altered receptor numbers since affinities for 125I-labeled PTH and CT remained unchanged. The effect on receptor levels was time dependent, requiring 24 h preincubation with TGF beta for measurable changes, and dose dependent, with maximal effects seen with 1 ng/ml TGF beta. Binding of [3H]1,25(OH)2 vitamin D3 was increased to 130% of control in cytosolic extracts of UMR 106-06 cells pretreated for 3 days with 1 ng/ml TGF beta. Scatchard plots suggested an increase in receptor number without change in affinity. The adenylate cyclase response to PTH increased to 150% of control cells after 3 days of treatment with 1 ng/ml TGF beta; however, the adenylate cyclase response to CT was little changed. Forskolin- and cholera toxin-stimulated adenylate cyclase responses were increased by TGF beta treatment to 130-160% of control, indicating an increase in the stimulatory subunit of the G protein. Increased abundance of both Gs and Gi proteins were indicated by increased cholera toxin- or pertussis toxin-dependent [32P] NAD ribosylation of 47-kilodalton (kDa) and 42-kDa or 40-kDa proteins, respectively, in TGF beta-treated cells. Our data support a complex regulatory effect of TGF beta on UMR 106-06 cells with increases in PTH receptors, vitamin D receptors, and G proteins, whereas there is an apparent down-regulation of CT receptors. TGF beta might induce a more differentiated osteoblast phenotype of these cells, which already express differentiated features such as high alkaline phosphatase activity, PTH and vitamin D receptors, and collagenase production. Since low doses of PTH stimulate bone formation in vivo, TGF beta released or activated at sites of new bone formation might locally modulate PTH activity be allowing increased PTH receptor and postreceptor effectiveness.

Adenylyl Cyclases↗
PubMed1992

Disulfide bond cleavage of human fibrinogen by cis-diamminedichloroplatinum(II).

Disulfide bridges in fibrinogen (Fbg) were cleaved by cis-diamminedichloroplatinum(II) (cis-DDP). Incubation with 120 molar excess of cis-DDP at pH 7.4 and 37 degrees C in the presence of EDTA resulted in cleavage of seven disulfide bridges out of 29. In the presence of calcium, however, the number of cleavages were reduced to four. The result indicates that calcium, which has three high affinity sites on Fbg, protects disulfide bridges from the rupture. Thrombin clottability was examined by turbidity measurement. The cis-DDP treated Fbg was shown to give a decreased fiber thickness. As the cleavage proceeded, the clotting ability of Fbg decreased.

Cisplatin↗
PubMed1992

Comparison of the effects of halothane and propranolol on the effective refractory period and the ventricular activation in a canine myocardial infarction model.

The effects of halothane on the effective refractory period (ERP) and the ventricular activation were examined in a canine myocardial infarction model, and compared with those of propranolol. Halothane reduced the heart rate and prolonged the ERP in both normal and infarcted zones. A prolongation of ERP with halothane was also observed during atrial pacing at the same rate as in control, but the effect was less than during sinus rhythm. Halothane (1 MAC) further delayed or blocked the delayed activation in the infarcted zones with only slight effects on the activation of the normal zones. Propranolol (0.2 mg/kg) prolonged ERP during sinus rhythm, but it did not affect either the ERP or ventricular activation during atrial pacing. In conclusion, halothane produced a selective depression of the delayed activation and the prolongation of ERP, which may be caused by both direct effects on the myocardium and secondary effects such as a reduction of the heart rate. These effects of halothane may contribute to its antiarrhythmic effects in the myocardial infarction model which have been previously reported.

Animals↗
PubMed1992

Synthesis and biological activities of optical isomers of 2-(4-chlorophenyl)-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)-o ne 7-oxide.

Two enantiomers of 2-(4-chlorophenyl)-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-one 7-oxide ((+/-)-1: Y-23684) were synthesized in high yields by asymmetric oxidation of the synthetic precursor (2) using modified Sharpless reagent. Among the oxidants tested, cumene hydroperoxide (CHP) gave the highest optical and chemical yields, while tert-butyl, tert-amyl, and 1,1,3,3-tetramethylbutyl hydroperoxides did not show such high enantio-selectivities. The absolute configuration of (+)-1 enantiomer synthesized from 2, Ti(O-iso-Pr)4, (-)-diethyl tartarate, and CHP was determined to be S by X-ray crystallographic analysis. Both enantiomers, S-(+)-1 and R-(-)-1, and (+/-)-1 had approximately equivalent in vivo activities to antibicuculline test in mice and anticonflict test in rats, although S-( + )-1 showed about three times higher affinity to benzodiazepine receptor than R-(-)-1 in [3H]diazepam binding assay.

Animals↗
PubMed1992

Histological and histochemical studies on developing ciliary body in eye of ICR mouse.

Histological and histochemical studies have been made on the microscopic structures of the ciliary body from the developing eyes of both pre- (on day 13, 16 and 18 of gestation) and postnatal (on day 1, 5, 10, 14 and 84) mice of the Jcl:ICR strain and on the acidic glycoconjugates contained in the ciliary body tissues of these animals. As the staining procedures of choice, a hematoxylin-eosin procedure and a sensitized high iron diamine method were employed. A nitrous acid procedure was used in combination for some tissue sections, prior to the sensitized diamine method, to aid in the identification of sulfated glycoconjugates. Both the partes optica and caeca retinae could be identified histochemically as early as day 13 of gestation, whereas these parts could not be histologically distinguished from each other at day 16 of gestation. The ciliary folds were detected first in the external layer at day 16 of gestation and subsequently in the internal layer 2 days later. The heparan sulphate proteoglycan observed not only in the thick basement membrane but also in the intra- and intercellular spaces of the internal layer was localized in a distribution pattern which prevented the occurrence of configurational discrepancies between the epithelial cells lining the layer because of the formation of ciliary folds.

Animals↗