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Biomedical subjects

S Kuroda

Publications and source records attributed to S Kuroda.

At least 55 records · Page 3Linked to original sources
PubMed2001

Familial amyotrophic lateral sclerosis with a novel Leu126Ser mutation in the copper/zinc superoxide dismutase gene showing mild clinical features and lewy body-like hyaline inclusions.

BACKGROUND: Mutations in the SOD1 gene are responsible for approximately 25% of all familial amyotrophic lateral sclerosis (ALS) cases. However, the correlation between the clinical and pathological features and the various SOD1 gene mutations has not been well characterized. OBJECTIVES: To screen the SOD1 gene in search of potential mutations and to obtain clinical and pathological data for 2 Japanese families with ALS. DESIGN: Clinical histories and neurological findings, gross and microscopic pathological features, and DNA analysis of the SOD1 gene. RESULTS: The 2 families with ALS showed a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation TTG to TCG, causing substitution of leucine for serine at codon 126 (Leu126Ser) in exon 5. Clinically, patients showed slower disease progression and lack of upper motor neuron signs. Neuropathologically, the autopsied patient showed the form of familial ALS with posterior column involvement, and the pontocerebellar tract and the dentate nuclei of the cerebellum were also involved. Furthermore, abundant Lewy body-like hyaline inclusions were observed in the affected motor and nonmotor neurons. CONCLUSIONS: Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed mild clinical features and lack of upper motor neuron signs. We believe that Leu126Ser might be associated with the clinical features and that the mutation site in the SOD1 gene and disease duration might be associated with the formation of Lewy body-like hyaline inclusions.

Adult↗
PubMed2001

A family with X-linked dystonia-deafness syndrome with a novel mutation of the DDP gene.

BACKGROUND: X-linked dystonia-deafness syndrome (DDS) is characterized by early-onset deafness followed by progressive dystonia in adulthood. Only 4 families with the syndrome have been reported, and all were white. OBJECTIVE: To describe the first nonwhite family with X-linked DDS, involving 5 affected males in 4 generations. RESULTS: Clinical features of the family members, who were Japanese, were mostly consistent with reports of DDS in whites except for a lack of visual disturbances. Whereas microdeletions in the deafness-dystonia peptide (DDP) gene were found in 2 white DDS families, our patients showed a novel mutation (arg80ter) in exon 2 of the DDP gene. CONCLUSION: The existence of a DDS family of Japanese origin with a new kind of mutation in the DDP gene provides additional evidence that the DDP gene is a causative gene for X-linked DDS.

Adolescent↗
PubMed2001

Prevalence of homozygous deletions of the parkin gene in a cohort of patients with sporadic and familial Parkinson's disease.

Mutation of the parkin gene is a cause of familial Parkinson's disease of the autosomal recessive form; however, its significance in all Parkinson's disease cases is unclear. Deletions in the parkin gene were found in only 2.2% of 184 Japanese patients with Parkinson's disease. However, deletions were present in 25.0% and 40.0% of the patients with juvenile-onset (< 40 y) and with familiality, respectively. On the other hand, deletions were not found in any adult-onset cases (> 40 y). Half of the patients with parkin gene-related Parkinson's disease lacked both heredity and consanguinity.

Age of Onset↗
PubMed2001

Impaired fertility in female mice lacking urinary trypsin inhibitor.

Urinary trypsin inhibitor (UTI) is a serine proteinase inhibitor that is found in blood and urine. To investigate the physiological functions of UTI in vivo, we generated UTI-deficient mice by gene targeting. The mice showed no obvious abnormalities and appeared healthy. However, the females displayed a severe reduction in fertility. Wild-type embryos developed normally when transplanted into UTI-deficient female mice, suggesting that UTI-deficient females have a normal ability to maintain pregnancy. The number of naturally ovulated oocytes from UTI-deficient mice was greatly reduced compared with that from wild-type mice. Histologically, oocytes with disorganized corona radiata were frequently seen in the ovaries of UTI-deficient mice after hormonal stimulation. When ovaries from UTI-deficient mice were transplanted into wild-type mice, pups derived from the transplanted ovaries were obtained, suggesting that the ovary of UTI-deficient mice functions normally if UTI is supplied from the systemic circulation. These results demonstrate that UTI plays an important role in the formation of the stable cumulus-oocyte complex that is essential for oocyte maturation and ovulation.

Animals↗
PubMed2001

Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins.

The Shank family of proteins (also termed CortBP, ProSAP, or Synamon) is highly enriched in the postsynaptic density (PSD) of excitatory synapses in brain. Shank contains multiple domains for protein-protein interactions, including ankyrin repeats, SH3 domain, PDZ domain, SAM domain, and an extensive proline-rich region. We have identified a novel protein, termed Sharpin, that directly interacts with the ankyrin repeats of Shank. Sharpin is enriched in the PSD and forms a complex with Shank in heterologous cells and brain. Immunostaining reveals the presence of Sharpin at excitatory synapses and its colocalization with Shank. While the C-terminal half of Sharpin interacts with Shank, the N-terminal half of Sharpin mediates homomultimerization. Considering the fact that the ankyrin repeats and the SH3 domain of Shank can be truncated by alternative splicing, these results define Sharpin as a novel PSD protein that may regulate the complexity of the Shank-based protein network in an alternative splicing-dependent manner.

Adaptor Proteins, Signal Transducing↗
PubMed2001

High frequency of beta-catenin mutations in hepatoblastoma.

Hepatoblastoma (HB) is an embryonic neoplasm representing the most frequent malignant liver tumour in childhood. Its tumourigenesis at the molecular level is still poorly understood, and candidate genes are yet to be identified. According to recent reports describing beta-catenin mutations (BCM) at hot-spot regions involving exon 3 in several types of malignancies including HB, we investigated BCM in 16 HBs classified into different histological types. One tumour had been previously confirmed to harbour adenomatous polyposis coli (APC) mutations that exhibit a similar oncogenic effect to that of BCM. Mutations in both exon 3 and its flanking region of the beta-catenin gene were investigated and determined. Twelve tumours (75%) revealed pathogenic BCM, including 5 with missense mutations at codons 32, 34, or 37 and 7 with interstitial deletions that partially or totally affected exon 3. All 7 deletions were in-frame deletions without frameshift. A single nucleotide change at codon 31 regarded as non-pathogenic polymorphism was detected in the tumour possessing APC mutations. Therefore, a total of 13 tumours (81%) were compromised by an enhanced beta-catenin-mediated transcription pathway. Mutations were observed in every histological type of HB. The very high frequency without correlation to histological type indicates that BCM are crucial events in the tumourigenesis of HB.

Child↗
PubMed2001

Distribution of basal ganglia lesions in generalized variant of Pick's disease: a clinicopathological study of four autopsy cases.

We investigated four Japanese autopsy cases of the generalized variant of Pick's disease ("basophilic inclusion body disease") both clinically and pathologically, and examined the degree and distribution of the basal ganglia lesions, including the amygdala, striatum, pallidum, and substantia nigra. The lesions in the amygdala, striatum, and pallidum were classified into three categories (slight, moderate, and severe). The lesions in the substantia nigra were qualitatively judged, compared with normal controls. Extrapyramidal signs, not noticed in the generalized variant of Pick's disease, were evident in all four cases, in addition to dementia. The degree and distribution of basal ganglia lesions in all four cases were uniform: the caudate nucleus showed severe lesions, the amygdala and putamen severe to moderate lesions, and the pallidum moderate to slight lesions. The substantia nigra in all our cases showed prominent neuronal loss, probably being one of the lesions responsible for extrapyramidal signs. In the generalized variant of Pick's disease, the degree and distribution of the alterations within the basal ganglia differs from those reported in Pick's disease with Pick bodies (PDPB) and corticobasal degeneration (CBD). In PDPB, severe lesions are present in the amygdala with relative sparing of the substantia nigra, compatible with rare extrapyramidal signs in PDPB, while in CBD, severe lesions are found in the pallidum and substantia nigra. These clinicopathological findings may contribute not only to the elucidation of clinicopathological hallmarks, but also to the progress of neuroimaging, in the generalized variant of Pick's disease.

Adult↗
PubMed2001

Plaque-like structures and arteriosclerotic changes in "diffuse neurofibrillary tangles with calcification" (DNTC).

"Diffuse neurofibrillary tangles with calcification" (DNTC) is a rare form of slowly progressive dementia characterized by temporal or fronto-temporal atrophy with neuronal loss and astrocytosis, neurofibrillary tangles and Fahr-type calcification, but no senile plaques in the cerebral cortex. In patients with DNTC, we detected a novel histopathological abnormality that we termed "plaque-like structures" (PLS). PLS appeared as oval, slightly eosinophilic masses of up to 100 microns in diameter. With methenamine silver stain, the PLS were argyrophilic, and thread-like structures were observed in and around them. Most PLS were observed in deep layers of the cortex and subcortical white matter, and were accompanied by small vessels. They were intimately associated with the small-vessel walls and astrocytes. They were composed of two types of fibers. The first type comprised straight and loosely interwoven fibers about 25-30 nm in diameter, while the other type evoked tangles. These structures have not been found in other neurodegenerative diseases, including Alzheimer's disease. In addition, to evaluate hyaline arteriosclerosis in DNTC, we examined sclerotic changes of the medullary arteries and assessed white matter lesions in affected patients. In three of four patients with DNTC, sclerosis of the medullary arteries was significantly more extensive than in age-matched controls. In all four patients, the severity of white matter lesions was graded as moderate or severe in the temporal lobe and as mild or moderate in the frontal lobe. Arteriosclerotic changes and white matter lesions can occur without hypertension and beta amyloid deposits in DNTC.

Amyloid beta-Peptides↗
PubMed2001

Statistical characteristics of climbing fiber spikes necessary for efficient cerebellar learning.

Mean firing rates (MFRs), with analogue values, have thus far been used as information carriers of neurons in most brain theories of learning. However, the neurons transmit the signal by spikes, which are discrete events. The climbing fibers (CFs), which are known to be essential for cerebellar motor learning, fire at the ultra-low firing rates (around 1 Hz), and it is not yet understood theoretically how high-frequency information can be conveyed and how learning of smooth and fast movements can be achieved. Here we address whether cerebellar learning can be achieved by CF spikes instead of conventional MFR in an eye movement task, such as the ocular following response (OFR), and an arm movement task. There are two major afferents into cerebellar Purkinje cells: parallel fiber (PF) and CF, and the synaptic weights between PFs and Purkinje cells have been shown to be modulated by the stimulation of both types of fiber. The modulation of the synaptic weights is regulated by the cerebellar synaptic plasticity. In this study we simulated cerebellar learning using CF signals as spikes instead of conventional MFR. To generate the spikes we used the following four spike generation models: (1) a Poisson model in which the spike interval probability follows a Poisson distribution, (2) a gamma model in which the spike interval probability follows the gamma distribution, (3) a max model in which a spike is generated when a synaptic input reaches maximum, and (4) a threshold model in which a spike is generated when the input crosses a certain small threshold. We found that, in an OFR task with a constant visual velocity, learning was successful with stochastic models, such as Poisson and gamma models, but not in the deterministic models, such as max and threshold models. In an OFR with a stepwise velocity change and an arm movement task, learning could be achieved only in the Poisson model. In addition, for efficient cerebellar learning, the distribution of CF spike-occurrence time after stimulus onset must capture at least the first, second and third moments of the temporal distribution of error signals.

Action Potentials↗
PubMed2001

Comparative analyses of the distribution of various transposable elements in Pyricularia and their activity during and after the sexual cycle.

We examined the distribution and activity of six transposable elements found in the blast fungus, Pyricularia spp. Sixty-eight isolates from various gramineous plants were used for the survey, and the elements were plotted on a dendrogram constructed on the basis of their rDNA-ITS2 sequences. MGR586 and Pot2 (Class II elements), Mg-SINE (SINE-like element) and MGR583 (LINE-like retrotransposon) were widely distributed among the Pyricularia isolates, suggesting that they are old elements which arose in, or invaded, the Pyricularia population at very early stages in its evolution. By contrast, the distribution of the LTR-retrotransposons MAGGY and Grasshopper was limited or sporadic, suggesting that they are relatively new elements which recently invaded the Pyricularia population by means of horizontal transfer events. The activity of these elements was evaluated by Southern analysis in progenies derived from a cross between a Setaria isolate and a Triticum isolate. Many new MAGGY signals were observed, which were absent in the parental isolates, at various stages of the sexual cycle and following vegetative growth. In contrast, the other elements yielded few, if any, such signals. Analysis of the sequences flanking the new MAGGY insertions revealed that they were each associated with a 5-bp target-site duplication at both ends of the insertion. These data suggested that MAGGY was the most active of the elements tested for transposition in Pyricularia.

Blotting, Southern↗
PubMed2001

Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria.

A 60-year-old Japanese man was diagnosed as having hypouricemia at an annual health check-up. The routine laboratory data was not remarkable except that the patient's hypouricemia and plasma levels of xanthine and hypoxanthine were much higher than those of normal subjects. Furthermore, the patient's daily urinary excretion of xanthine and hypoxanthine was markedly increased compared with reference values. The xanthine dehyrogenase activity of the duodenal mucosa was below the limits of detection. Nevertheless, allopurinol was metabolized to oxypurinol in vivo. Based on these findings, a subtype of classical xanthinuria (type I) was diagnosed. The xanthine dehyrogenase protein was detected by Western blotting analysis. Sequencing of the cDNA of the xanthine dehyrogenase obtained from the duodenal mucosa revealed that a point mutation of C to T had occurred in nucleotide 445. This changed codon 149 from CGC (Arg) to TGC (Cys), a finding that has not been previously reported in patients with classical xanthinuria type I.

Allopurinol↗
PubMed2001

Intraoperative measurement of arterial blood flow using a transit time flowmeter: monitoring of hemodynamic changes during cerebrovascular surgery.

BACKGROUND: The purpose of this study was to examine the utility and reliability of arterial flow measurements made with a transit time ultrasonic flowmeter for monitoring blood flow changes during intracranial and carotid surgery. METHOD: A total of 25 patients underwent intra-operative arterial blood flow measurements. The pulsatile flow curve and mean flow values were obtained using 1- to 6-mm transit time probes with a dual channel flowmeter. Four cases underwent aneurysm clipping, 11 cases superficial temporal artery (STA)--middle cerebral artery (MCA) bypass, 2 cases external carotid artery (ECA)--radial artery--MCA bypass for aneurysm trapping, and 8 cases carotid endarterectomy. In aneurysm clipping, blood flow in the branches distal to the aneurysm was measured before and after clipping. Blood flow in the STA was measured before and after STA-MCA anastomosis, and blood flow in the internal carotid artery (ICA) cervical portion was measured during carotid endarterectomy. Blood flow in the MCA and STA was monitored during radial artery grafting. FINDINGS: Blood flow in the STA was elevated after STA-MCA anastomosis. However, post-operative hyperperfusion syndrome was found in some cases whose flow elevation was over 50 ml/min. Also in one case of carotid stenosis, of which blood flow of ICA was elevated to 400 ml/min after carotid endarterectomy, hyperperfusion syndrome was found after surgery. In the cases of MCA aneurysm clipping, decreasing of M2 flow was detected when clipping caused bifurcation stenosis. INTERPRETATION: We found transit time flow measurement useful for management of cerebrovascular surgery: the technique was simple to use and provided stable, reliable results. The method was able to reveal distal branch flow diminution in aneurysm clipping, or residual flow during temporary clipping in aneurysm surgery, and has the potential to predict post-operative complications such as hyperperfusion by signalling over-elevation of donor artery flow in bypass surgery or ICA flow in carotid surgery.

Adolescent↗
PubMed2001

IQGAP1, a negative regulator of cell-cell adhesion, is upregulated by gene amplification at 15q26 in gastric cancer cell lines HSC39 and 40A.

Our previous comparative genomic hybridization (CGH) study revealed a novel amplified region at 15q26 in two cell lines established from diffuse types of gastric cancer (GC). In this amplified region, FES and IGF1R, known targets on 15q26, were located telomeric to the amplicon in the two cell lines, HSC39 and 40A, suggesting that another tumor-associated gene exists in this region. While screening expressed sequence tags (ESTs) for novel genes in this region, we identified the IQGAP1 amplification. IQGAP1 has been reported to encode a ras GAP-related protein, and its interaction with cadherin and/or beta-catenin induces a dissociation of beta-catenin from the cadherin-catenin complex, one of the mechanisms for cell-cell adhesion. Northern and Western blot analyses revealed that amplification of this gene was accompanied by corresponding increases in mRNA and protein expression. Moreover, immunocytochemical staining showed that overexpressed IQGAP1 accumulated at the membrane, suggesting its colocalization with beta-catenin. Taken together, these findings suggest that IQGAP1 may be one of the target genes in the 15q26 amplicon correlated with a malignant phenotype of gastric cancer cells, such as diffuse and invasive characteristics, through the disruption of E-cadherin-mediated cell-cell adhesion.

Carrier Proteins↗
PubMed2001

Treatment outcome of single or hypofractionated single-isocentric stereotactic irradiation (STI) using a linear accelerator for intracranial arteriovenous malformation.

BACKGROUND AND PURPOSE: We investigated the use of hypofractionated stereotactic radiotherapy (HFSR) to reduce adverse radiation effects in comparison to single-fraction stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (AVMs). MATERIALS AND METHODS: This study includes 53 intracranial AVMs treated between 1991-1998. HFSR was selected for 26 AVMs with a maximum diameter > or 2.5 cm or at eloquent area. Twenty-seven patients were treated with SRS (18 AVMs < 2.5 cm at non-eloquent area, nine patients who were unfit for prolonged ring-wearing). The most frequent minimum dose (Dmin) was 20 Gy for SRS and 28 Gy for HFSR in four fractions. The mean follow-up duration was 34.6 months for SRS and 35.4 months for HFSR. RESULTS: As a whole, the 3 and 5-year actuarial obliteration rates were 64 and 92%. Age <20 years old (P=0.02) and a maximum diameter <2 cm were favorable factors (P=0.05). A difference in the distribution of patients was observed in size (> or =2.5 cm or not) (P<0.001) and location (eloquent or not) (P<0.001) between SRS and HFSR due to the treatment selection. However, no significant differences were observed in the actuarial rates of obliteration and transient increased signals with T2-weighted MR images between SRS and HFSR. Radiation necrosis occurred in two patients treated with SRS and in none with HFSR. Intracranial hemorrhage after treatment happened in two treated with SRS and three with HFSR. CONCLUSIONS: HFSR appears to be at least as effective as SRS in achieving complete obliteration of intracranial AVM, although its definitive role remains to be investigated.

Adolescent↗
PubMed2001

The insular but not the perirhinal cortex is involved in the expression of fully-kindled amygdaloid seizures in rats.

We have previously reported an important excitatory role of the perirhinal cortex (PRC) in rat kindling development using an immunohistochemistry technique. In this study, we investigated the roles of the PRC and the insular cortex (INS) located rostral to the PRC, in fully-kindled amygdaloid seizures, using a microinjection technique in the rat kindling model of epilepsy. Following the establishment of daily kindling, we investigated the effects of microinjections of procaine hydrochloride, 2-amino-5-phosphonovalerate (APV; an N-methyl-D-aspartate (NMDA) receptor antagonist) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX; an alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor antagonist). Microinjections of these drugs into the ipsilateral PRC did not suppress kindled seizures. The possibility is that the process of kindling development forms novel seizure-generalization pathways that do not require further activation of the PRC. On the other hand, procaine and APV injected into the ipsilateral INS significantly suppressed kindled seizures. The manner of suppression appeared to be 'all or none'. It is therefore possible that at least the activation of NMDA receptors in the INS is necessary to express generalized kindled amygdaloid seizures.

Amygdala↗
PubMed2001

Terminal deoxynucleotidyltransferase is negatively regulated by direct interaction with proliferating cell nuclear antigen.

BACKGROUND: The repertoires of Ig and TcR are generated by a combinatorial rearrangement of variable (V), diversity (D), and joining (J) segments (V(D)J recombination) in B- and T-cells. Terminal deoxynucleotidyltransferase (TdT) adds extra nucleotides (N nucleotides) at the junctions of the gene segments to enhance the Ig and TcR genes diversity. Using an anti-TdT antibody column, TdT has been purified as a member of a megadalton protein complex from rat thymus. The N region would be synthesized with the large protein complex. RESULTS: The cDNAs for proliferating cell nuclear antigen (PCNA) were isolated by yeast two-hybrid screening as the gene products which directly interacted with TdT. The interaction between PCNA and TdT was confirmed by co-immunoprecipitation, both in vitro and in vivo. TdT binds directly to a PCNA trimer, as shown by gel filtration. TdT interacts with PCNA in its DNA polymerization domain (DPD), but not in its BRCA-1 C-terminal (BRCT) domain. TdT activity was reduced to 17% of the maximum value by TdT/PCNA complex formation. CONCLUSION: TdT interacts directly with PCNA through its DPD. A functional consequence of this interaction is the negative regulation of TdT activity. These findings suggest that TdT catalyses the addition of N nucleotides under the negative control of PCNA during V(D)J recombination.

Binding Sites↗
PubMed2001

Involvement of a urethane-sensitive system in timing the onset of gastrulation in Xenopus laevis embryos.

This paper describes success in delaying the onset of gastrulation in Xenopus laevis embryos without damage to their subsequent development by temporarily arresting cleavage with urethane. Exposure of X. laevis embryos to 150 mM urethane before gastrulation resulted in cleavage arrest and its removal led to cleavage resumption. During cleavage arrest, cyclic activities including nuclear replication and the M-phase-promoting factor cycle continued, although their duration was lengthened to nearly 1.8-fold that of the controls. Because of a 30-min time lag from removal of urethane to resumption of cleavage, as well as the retardation of cyclic activities during cleavage arrest, the development of embryos after a 60-min exposure to urethane lagged two cell cycles behind that of control embryos. Here, the two cell cycle delay is equivalent to 50 min at 22-23 degrees C. The start of gastrulation in exposed embryos was accordingly delayed about 50 min, although the delay in mid-blastula transition was as little as 20-25 min. Consistent results were obtained in embryos exposed to urethane for 90 or 120 min and those exposed to procaine or NH4Cl for 60 min. Although these results imply that delay in the start of gastrulation in exposed embryos is ascribed simply to delay in their development raised by cleavage arrest, at the same time they suggest that the onset of gastrulation is timed by systems sensitive to urethane, procaine and NH4Cl in X. laevis embryos.

Ammonium Chloride↗