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Biomedical subjects

S Kuroda

Publications and source records attributed to S Kuroda.

At least 91 records · Page 5Linked to original sources

[Two cases of "steal VBI" with stenosis of the internal carotid artery].

Although previous reports have suggested "steal VBI" due to occlusive carotid artery diseases, there have been no reports that clearly define "steal VBI" from the viewpoint of cerebral hemodynamics. The authors presented two cases with "steal VBI" due to severe stenosis of the internal carotid artery. Both patients had well-developed collateral circulation through the ipsilateral posterior communicating artery. Although no occlusive lesion was found in the vertebrobasilar system, blood flow studies revealed impaired hemodynamics in the contralateral occipital lobe, which fact correlated with their neurological deficit, visual field disturbance. Carotid stenting markedly corrected the stenotic lesions, leading to neurological improvement. Follow-up blood studies showed normalization of hemodynamics in the contralateral occipital lobe. The findings strongly suggest that carotid surgery or stenting can improve cerebral hemodynamics in the carotid systems, resolving "steal VBI" due to developed collaterals from the posterior to the anterior circulation.

Carotid Artery, Internal↗

Identification of missense mutation (G365R) of the butyrylcholinesterase (BCHE) gene in a Japanese patient with familial cholinesterasemia.

A point mutation which caused a silent phenotype of human serum butyrylcholinesterase (BChE) was identified in the genomic DNA of a 57-year-old Japanese woman who visited our hospital because of pneumonia. The propositus exhibited an unusually low level of BChE activity, whereas her son and daughter had an intermediate level. Immunologically, there was an absence of BChE protein in the propositus's serum. DNA sequence analysis of the propositus demonstrated a point mutation at codon 365 (GGA-CGA), resulting in a Gly-Arg substitution. A family study showed her son and daughter to have the same mutation.

Butyrylcholinesterase↗

[Angioplasty with stenting for intracranial vertebral and basilar artery stenosis: three technical case reports and literature review].

Patients with intracranial vertebral artery (VA) or basilar artery (BA) stenosis have been mainly treated with medication. However, it has been reported that about 10% of patients experience restroke in the VBA territory, with a high rate of morbidity and mortality. Percutaneous transluminal angioplasty (PTA) is regarded as one of the treatments although it carries the risk of restenosis, recoil or dissection. Stent placement is, therefore, considered to be a further option for the treatment of intracranial artery stenosis since it can prevent the restenosis. We report three medical refractory cases of intracranial VA (2 cases) or BA stenosis (1 case) treated with stenting, none of which had complications and their symptoms disappeared or diminished. Angioplasty with the use of a stent device is regarded as a useful treatment for intracranial artery stenosis, but its risk and long-term result need to be investigated further.

Aged↗

[Intentional neck-plastic incomplete clipping followed by coil embolization for broad-necked distal BA aneurysms].

OBJECTIVE: We report three patients with broad-necked distal basilar artery (BA) aneurysms treated with intentional incomplete clipping followed by endovascular occlusion using Guglielmi detachable coils. METHODS: The location of the aneurysms was BA bifurcation in one patient and BA-superior cerebellar artery (SCA) in two. One patient presented with acute subarachnoid hemorrhage and two patients had incidental aneurysms. In two patients, endovascular treatment was thought to be difficult considering the morphology of the aneurysms and surgical treatment was performed as the first choice of treatment. One patient with a BA-SCA aneurysm underwent endovascular treatment using a remodelling technique first. However, it was impossible to place the coil preserving SCA, so surgical treatment was performed. In all patients, the attempt to pursue complete clipping was considered to be accompanied with high risks of morbidity, so neck-plastic incomplete clipping was performed intentionally. One to six days after the surgery, coil embolization was performed. RESULTS: In all patients, complete occlusion of the aneurysms was achieved and all patients had excellent clinical outcomes. CONCLUSION: Intentional neck-plastic incomplete clipping followed by endovascular coiling may be a useful treatment option for patients with broad-necked distal BA aneurysms.

Aged↗

Identification of CRAM, a novel unc-33 gene family protein that associates with CRMP3 and protein-tyrosine kinase(s) in the developing rat brain.

Four members of collapsin response mediator proteins (CRMPs) are thought to be involved in the semaphorin-induced growth cone collapse during neural development. Here we report the identification of a novel CRMP3-associated protein, designated CRAM for CRMP3-associated molecule, that belongs to the unc-33 gene family. The deduced amino acid sequence reveals that the CRAM gene encodes a protein of 563 amino acids, shows 57% identity with dihydropyrimidinase, and shows 50-51% identity with CRMPs. CRAM appears to form a large complex composed of CRMP3 and other unidentified proteins in vivo. Indeed, CRAM physically associates with CRMP3 when co-expressed in COS-7 cells. The expression of CRAM is brain-specific, is high in fetal and neonatal rat brain, and decreases to very low levels in adult brain. Moreover, CRAM expression is up-regulated during neuronal differentiation of embryonal carcinoma P19 and PC12 cells. Finally, immunoprecipitation analysis of rat brain extracts shows that CRAM is co-immunoprecipitated with proteins that contain protein-tyrosine kinase activity. Taken together, our results suggest that CRAM, which interacts with CRMP3 and protein-tyrosine kinase(s), is a new member of an emerging family of molecules that potentially mediate signals involved in the guidance and outgrowth of axons.

Adaptor Proteins, Signal Transducing↗

Tau pathology in diffuse neurofibrillary tangles with calcification (DNTC): biochemical and immunohistochemical investigation.

Diffuse neurofibrillary tangles with calcification (DNTC) represents a primary and sporadic presenile dementia that is characterized by temporal or fronto-temporal atrophy with diffuse neurofibrillary tangles (NFTs), neuropil threads and Fahr-type calcification without senile plaques. We examined the tau pathology in five autopsy cases of DNTC by immunoblotting and immunohistochemistry using phosphorylation-dependent and -independent anti-tau antibodies. The pattern of staining for different epitopes of beta-amyloid (A beta) was also investigated. NFTs were immunopositive with all the anti-tau antibodies used in this study. On the immunoblots, sarkosyl-insoluble tau appeared as three major bands of 60, 64 and 68 kDa, and as a minor band at 72 kDa. The majority of extracellular NFTs were weakly immunopositive only with the antibody recognizing the 40 carboxyl-terminal of A beta in DNTC. These results suggest that Alzheimer's disease-like tau pathology could exist independently of A beta deposits in DNTC.

Aged↗

An open conformation of switch I revealed by the crystal structure of a Mg2+-free form of RHOA complexed with GDP. Implications for the GDP/GTP exchange mechanism.

Mg(2+) ions are essential for guanosine triphosphatase (GTPase) activity and play key roles in guanine nucleotide binding and preserving the structural integrity of GTP-binding proteins. We determined the crystal structure of a small GTPase RHOA complexed with GDP in the absence of Mg(2+) at 2.0-A resolution. Elimination of a Mg(2+) ion induces significant conformational changes in the switch I region that opens up the nucleotide-binding site. Similar structural changes have been observed in the switch regions of Ha-Ras bound to its guanine nucleotide exchange factor, Sos. This RHOA-GDP structure reveals an important regulatory role for Mg(2+) and suggests that guanine nucleotide exchange factor may utilize this feature of switch I to produce an open conformation in GDP/GTP exchange.

Binding Sites↗

ENH, containing PDZ and LIM domains, heart/skeletal muscle-specific protein, associates with cytoskeletal proteins through the PDZ domain.

The Enigma homologue protein (ENH), containing an N-terminal PDZ domain and three C-terminal LIM domains, is a heart and skeletal muscle-specific protein that has been shown to preferentially interact with protein kinase C beta (PKCbeta) through the LIM domains (Kuroda et al., J. Biol. Chem. 271, 31029-31032, 1996). We here demonstrate that ENH is colocalized with a cytoskeletal protein alpha-actinin in the Z-disk region of rat neonatal cardiomyocytes. Pull-down assays using the glutathione-S-transferase-fusion system also showed the interaction of the PDZ domain of ENH with actin and alpha-actinin. Furthermore, by combined use of the in silico and conventional cDNA cloning methods, we have isolated three ENH-related clones from a mouse heart-derived cDNA library: mENH1 (591 amino acid residues) corresponding to rat ENH, mENH2 (337 residues), and mENH3 (239 residues); the latter two containing only a single PDZ domain. Deciphering their cDNA sequences, these mENH1-3 mRNAs appear to be generated from a single mENH gene by alternative splicing. Northern blot analyses using human cancer cells and mouse embryos have shown expression of each mENH mRNA to vary considerably among the cell types and during the developmental stage. Together with a recent finding that PKCbeta is markedly activated in the cardiac hypertrophic signaling, these results suggest that ENH1 plays an important role in the heart development by scaffolding PKCbeta to the Z-disk region and that ENH2 and ENH3 negatively modulate the scaffolding activity of ENH1.

Actinin↗

Methamphetamine decreases calcium-calmodulin dependent protein kinase II activity in discrete rat brain regions.

A Ca(2+)/calmodulin-dependent signaling cascade has been implicated in the regulation of dopaminergic neurotransmission after chronic administration of amphetamine and methamphetamine (METH). We found a decrease in Ca(2+)/calmodulin-dependent protein kinase II (CaM-kinase II) activity in five regions of the rat brain (parietal cortex; frontal cortex; hippocampus; striatum; and nucleus accumbens) after a single injection of METH. Pretreatment with the selective dopamine D1 receptor antagonist SCH 23390 prevented the acute METH-induced decrease in CaM-kinase II activity in the parietal cortex, striatum, nucleus accumbens, and substantia nigra/ventral tegmental area (SN/VTA). Pretreatment with the N-methyl-D-aspartate receptor antagonist MK-801 significantly restored the acute METH-induced decrease in CaM-kinase II activity in the parietal cortex, nucleus accumbens, and SN/VTA. Striatal CaM-kinase II activity was still significantly lower than that of the chronic saline-treated controls after a 1-week, but not a 4-week, abstinence from chronic administration of METH. A METH challenge after a 4-week abstinence period induced a more pronounced decrease in CaM-kinase II activity in rats chronically injected with METH than in rats chronically injected with saline. Western blot analysis revealed that the amount of CaM-kinase II protein was not altered after a single METH injection or after chronic METH injections, compared with saline-treated controls. However, amounts of phosphorylated (Thr(286)) CaM-kinase II in the parietal cortex, striatum and SN/VTA were significantly decreased at 3 h after an acute METH injection compared with saline-treated controls. These results suggest that dephosphorylation of CaM-kinase II may contribute to the decreased enzyme activities induced by acute METH administration, and that chronic treatment with METH leads to an enhanced capacity of METH to decrease CaM-kinase II activity after an extended withdrawal period.

Animals↗

Increment of synapsin I immunoreactivity in the hippocampus of the rat kindling model of epilepsy.

Synapsin is a vesicle-associated protein that is thought to be involved in synaptogenesis and neurotransmitter release. In this study, we investigated the repeated amygdala kindling-induced changes in levels of synapsin I, a marker of enhanced synaptic activity, using immunohistochemistry. Eight hours after the last seizure, synapsin I immunoreactivity (IR) was increased bilaterally in the polymorphic zone of the dentate gyrus, the hilus and the stratum lucidum in area CA3 of the hippocampus. However, 4 weeks after the last kindled seizures, synapsin I IR was not significantly changed in any of the brain regions studied. Therefore, the increased levels of synapsin I protein observed in these brain regions early after the last seizure may reflect the plastic changes that occur in the specific neural networks of the hippocampus directly after kindling-induced seizure activity.

Amygdala↗

Immunocytochemical localization of a neuron-specific thrombospondin-1-like protein, NELL2: light and electron microscopic studies in the rat brain.

We have studied the cellular and intracellular localization of NELL2, a neural thrombospondin-1-like protein. NELL2 protein was detected as doublet bands of 140 and 90 kDa with the use of the specific antibodies raised against the C-terminal region of NELL2 and was recognized only in the brain but not in the peripheral tissues. Within the brain, NELL2 was abundantly present in the hippocampus and cerebral cortex, found moderately in the olfactory bulb and hypothalamus, and at a low level in the thalamus, cerebellum, and medulla. Immunocytochemically, NELL2 was seen only in neurons but not in glial cells or in the white matter. NELL2-immunoreactive cells were distributed throughout the brain with the highest density in the hippocampus and cerebral cortex. NELL2 was mainly found in the cell bodies of neurons and the immunoreactivity was often seen as dots in the perikarya. The distribution of NELL2 immunoreactivity did not completely correspond to that of any subtypes of protein kinase C (PKC). Under electron microscopy, NELL2 protein was associated with the endoplasmic reticulum (ER), especially with rough ER. NELL2 immunoreactivity was found in the restricted parts of the ER and found commonly inside the ER. These results suggest that NELL2 protein is synthesized by neurons and may be secreted from the neurons involved in certain neuronal functions.

Animals↗

Expression of DNA topoisomerase I, IIalpha, and IIbeta in human brain tumors.

We investigated the expression of DNA topoisomerase I (Topo I), IIalpha (Topo IIalpha), and IIbeta (Topo IIbeta) mRNA using reverse transcription-polymerase chain reaction (RT-PCR) assay in 31 human brain tumors, and examined the relationship between DNA topoisomerase mRNA expression and Topo IIalpha and MIB-1 positive index (PI) as a cell proliferation marker. Topo IIalpha mRNA was expressed in 11 of 31 cases, and Topo I and IIbeta were each expressed in 18 of 31 cases. A significant correlation was seen between the MIB-1 PI and Topo IIalpha PI (P < 0.001). The cases with overexpression of Topo IIalpha mRNA had significantly high MIB-1 and Topo IIalpha PI (P < 0.0001). There was no significant correlation between Topo I and IIbeta mRNA expression and MIB-1 PI. We concluded that it was useful as a cell proliferation marker to analyze the expression of Topo IIalpha mRNA using RT-PCR in human brain tumors.

Adult↗

Angiomyolipoma arising in the thigh.

A 41-year-old man presented with an asymptomatic mass in the right medial thigh. Magnetic resonance imaging (MRI) revealed a well-demarcated, 10-cm mass in the right adductor muscles. The margins of the mass exhibited high signal intensity and the rest showed low or iso signal intensity on T1-weighted MR images. However, the high signal intensity was decreased on T2-weighted images with fat suppression. The central part of the tumor was of inhomogeneous high signal intensity on T2-weighted images; after Gd-DTPA injection it enhanced in homogeneously on T1-weighted images with fat suppression. On dynamic computed tomography (CT) in the arterial phase, there were strongly enhancing spotty areas in the tumor. At surgery, a yellow-whitish tumor was resected and a pathological diagnosis of angiomyolipoma (AML) in the thigh was made.

Adipose Tissue↗

Identification and characterization of PRKCBP1, a candidate RACK-like protein.

The receptors for activated C-kinase (RACK) family of proteins function as anchors for activated protein kinase C (PKC) isoenzymes. Using a monoclonal antibody to RACK1 in the screening of a human hippocampus cDNA library, we identified a novel member of the RACK family, designated PRKCBP1. Immunoprecipitation assays performed with a GST-fused PRKCBP1 protein suggest the carboxy terminus of PRKCBP1 interacts specifically with PKCbetaI. Northern analysis detected a 3.1-kb PRKCBP1 transcript in all tissues examined including brain, heart, liver, lung, pancreas, skeletal muscle, kidney, and spleen. The PRKCBP1 gene has been localized to human Chromosome (Chr) 20q12-13.1. Several groups have reported evidence for genetic linkage of Type II diabetes to this region in Caucasian families. This localization, combined with the observation that abnormalities in the activation, translocation, and inhibition of PKC occur in the development of Type II diabetes, suggested that PRKCBP1 was a candidate for contributing to Type II diabetes. We determined the PRKCBP1 coding sequence is 1845 bp in length, dispersed over 9 exons, spanning approximately 34 kb of genomic DNA. SSCP analysis was used to screen PRKCBP1 coding regions for mutations or polymorphisms in 100 Caucasian Type II diabetics and 100 Caucasian unaffected individuals. A silent C/T transition (bp1413, Thr137) was present in 23% of both diabetic and control individuals. A C/T transition (bp198) was also identified in a single diabetic individual, which resulted in no coding change (Ser66). The results of this analysis suggest that PRKCBP1 coding variations are uncommon and do not contribute to Type II diabetes in the general population.

Amino Acid Sequence↗

Tau-negative astrocytic star-like inclusions and coiled bodies in dementia with Lewy bodies.

To evaluate glial lesions in cases of dementia with Lewy bodies (DLB), we studied the brains of four patients with DLB. Astrocytic star-like inclusions, which resembled tufted astrocytic fibrillary tangles in shape, were found in the cortex of two of these cases. In addition, coiled bodies were found in the white matter of the cerebrum in two cases. The astrocytic star-like inclusions were immunohistochemically negative for tau protein, ubiquitin and alpha-synuclein. The coiled bodies were immunohistochemically negative for tau protein but immunopositive for ubiquitin and alpha-synuclein. These results suggest that in DLB a primary degenerative process takes place in both glial cells and neurons.

Aged↗

Neovascularization (angiogenesis) after revascularization in moyamoya disease. Which technique is most useful for moyamoya disease?

The effects of direct and indirect revascularization for moyamoya disease were analyzed for each donor artery to determine which surgical procedure is most useful for the induction of neovascularization. In the past 12 years, 85 patients with moyamoya disease were surgically treated by combined surgery consisting of indirect revascularization via encephalo-duro-arterio-myo-synangiosis (EDAMS) and direct revascularization via the superficial temporal artery and the middle cerebral artery (STA-MCA) bypass. Among those patients, the post-operative changes in digital subtraction angiography were examined in 56 sides, including 34 sides in paediatric cases and 22 sides in adult cases. The neovascularization after indirect revascularization using the 1) superficial temporal artery (skin), 2) middle meningeal artery (dura mater), 3) deep temporal artery (temporal muscle) was analyzed. As results, in paediatric cases, the deep temporal artery and middle meningeal artery induced good neovascularization. However, the induction of neovascularization from the superficial temporal artery was not always good in most pediatric and adult cases. On the other hand, the direct bypass was useful in 90% of adult cases. In indirect revascularization surgery for moyamoya disease, the temporal muscle (the deep temporal artery) and the dura mater (the middle meningeal artery) are useful donors to the ischemic brain. The simple encephalo-arterio-synangiosis is not always effective. The direct bypass is a useful technique for adult moyamoya disease.

Adult↗

Operative record using intraoperative digital data in neurosurgery.

BACKGROUND: The purpose of this study was to develop a new method for more efficient and accurate operative records using intra-operative digital data in neurosurgery, including macroscopic procedures and microscopic procedures under an operating microscope. METHODS: Macroscopic procedures were recorded using a digital camera and microscopic procedures were also recorded using a microdigital camera attached to an operating microscope. Operative records were then recorded digitally and filed in a computer using image retouch software and database base software. FINDINGS: The time necessary for editing of the digital data and completing the record was less than 30 minutes. Once these operative records are digitally filed, they are easily transferred and used as database. Using digital operative records along with digital photography, neurosurgeons can document their procedures more accurately and efficiently than by the conventional method (handwriting). INTERPRETATION: A complete digital operative record is not only accurate but also time saving. Construction of a database, data transfer and desktop publishing can be achieved using the intra-operative data, including intra-operative photographs.

Humans↗

Enzyme-linked immunosorbent assay for anti-tropomyosin antibodies and its clinical application to various heart diseases.

Tropomyosin is one of the key proteins for muscle contraction. We developed an enzyme-linked immunosorbent assay for antibodies to porcine muscle tropomyosin and measured serum anti-tropomyosin antibodies in patients with heart diseases and in normal controls. The mean values of absorbance in the ELISA assay of patients with ischemic heart disease (n=36, P<0.001), dilated cardiomyopathy (n=28, P<0.005), valvular heart disease (n=27, P<0.05), and collagen disease (n=38, P<0.05) were significantly higher than those of normal controls (n=53), but the value in patients with hypertrophic cardiomyopathy (n=19) was not significantly different from that of normal controls. When the cut-off value was fixed at the mean+2 SD of absorbance in normal controls, positive reactions were found in 19.4%, 7.1%, 18.5% and 15.8% of patients with ischemic heart disease, dilated cardiomyopathy, valvular heart disease, and collagen disease, respectively. An inhibition study revealed that anti-tropomyosin antibodies were different from anti-myosin antibodies, but there was a partial cross-reactivity between the two. Thus, there was a weak correlation of the titers of the two types of antibody within the group of heart diseases. These data indicate that measurement of anti-tropomyosin antibodies by ELISA is helpful for detecting autoimmune abnormalities in various heart diseases.

Adult↗