Biomedical subjects

Yasuhiro Kuroda

Publications and source records attributed to Yasuhiro Kuroda.

At least 19 recordsLinked to original sources

PubMed2007

Short-latency somatosensory evoked potentials in infantile autism: evidence of hyperactivity in the right primary somatosensory area.

Children with infantile autism sometimes show hyperesthesia or hypoesthesia to touch, pain, and/or temperature. To clarify the pathophysiology, we examined short-latency somatosensory evoked potentials (S-SEPs), elicited by median nerve stimulation, in 24 children with infantile autism (17 males, seven females; age range 2y 2mo-9y; mean age 4y 2mo [SD 1y 7mo]). We also evaluated relationships between S-SEP findings and clinical manifestations. Of the 24 children, 10 showed abnormal S-SEPs as follows: prolonged peak latency of N20 (n=2), extended interpeak latency of P13/14-N20 (n=7), appearance of a giant SEP (n=1), and a more than twofold right hemispheric peak-to-peak amplitude predominance of N20-P25 (n=5). In addition, a peak-to-peak amplitude of N20-P25 elicited by left median nerve stimuli was significantly higher than that obtained with right median nerve stimuli, which indicated right hemispheric hyperactivity relative to the left (p=0.008). Infantile autism is frequently associated with somatosensory abnormalities and right hemispheric hyperactivity relative to the left, especially in the primary somatosensory area. This is believed to contribute to the pathophysiology of infantile autism, especially the idiopathic form.

Autistic Disorder↗

PubMed2006

Patients with West syndrome whose ictal SPECT showed focal cortical hyperperfusion.

To clarify the mechanism of clustered spasms in West syndrome (WS), we examined ictal SPECT and EEG, as well as those during the interictal period, in three patients with symptomatic WS who had apparent focal cerebral lesions. For ictal SPECT and EEG, we monitored the patients with EEG, and as soon as we noticed the occurrence of clustered spasms clinically and electroencephalographically, [(99m)Tc]ECD was injected intravenously and flushed thoroughly with saline. In these three patients, regional cerebral blood flow (rCBF) increased during ictus and decreased during the interictal period in the area that coincided with the focal cerebral lesion recognized by CT/MRI. The ictal hyperperfusion of bilateral basal ganglia was also detected in two of the three patients. The ictal EEG showed a diffuse slow wave complex corresponding to a clinical spasm. The sharp waves that preceded the diffuse slow wave complex and the spasm appeared in the same area in which rCBF increased during ictus. None of the patients showed partial seizure before or after clustered spasms clinically or electroencephalographically during the ictal SPECT study. Secondary generalization from a cerebral focus may explain the mechanism of spasms in these patients with WS: focal cortical discharge may primarily generate clustered spasms and trigger the brainstem and basal ganglia structures to produce spasms.

Cerebral Cortex↗

PubMed2006

Chemoenzymatic synthesis of a MUC1 glycopeptide carrying non-natural sialyl TF-beta O-glycan.

A MUC1 type of glycopeptide was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS) protocol using benzyl and benzylidene-protected beta-D-Gal-(1-->3)-beta-D-GalNAc-Ser/Thr (TF-beta: a stereoisomer of the Thomsen-Friedenreich antigen). The synthetic glycopeptide was released from the resin with reagent K, and the resulting benzylated glycopeptide was deprotected under conditions of low-acidity trifluoromethanesulfonic acid (TfOH). The glycopeptide carrying duplicate non-natural O-glycans was dominant in the products, but was accompanied by a considerable amount of the glycopeptide missing one of the O-glycans. In contrast, the native alpha-glycoside was relatively stable under the acidic debenzylation conditions as shown by a parallel experiment with the glycopeptide involving alpha-D-GalNAc-Ser/Thr linkage. Enzymatic glycosylation with CMP-NeuAc was successful with both natural and non-natural O-glycans of the synthetic glycopeptide.

Antigens, Neoplasm↗

PubMed2006

Metaphyseal dysplasia of Braun-Tinschert type: report of a Japanese girl.

We report on a 7-year-old Japanese girl with metaphyseal dysplasia (MD) of Braun-Tinschert type, a recently recognized, autosomal dominant sclerosing bone dysplasia. All individuals with the disorder from four families in the literature originated from a small town in Bohemia or its vicinity. The occurrence of the disorder in a Japanese girl indicates that it is not restricted to Germans. The radiographic hallmarks of the disorder include metaphyseal undermodeling (Erlenmeyer-flask deformity); osteosclerosis of the chondroosseous junctions, metaphyseal cortices, and epiphyseal margins; and exostosis-like bone excrescences at the metaphyseal-diaphyseal junctions. In the girl we described, the latter two findings were conspicuous at age 4 years, but became less prominent with increasing age. The metaphyseal trabeculae were somewhat coarse. The humeri exhibited varus deformity, and the ulnae and fibulae mild bowing. The mean bone mineral density of the lumbar spine was lower than that of age-matched controls. The patient exhibited premature loss of primary teeth, likely to be a sign of increased periodontal bone resorption. Markers of bone formation and resorption were both increased, an indication of a high rate of bone turnover.

Abnormalities, Multiple↗

PubMed2006

Favorable response of ADHD with giant SEP to extended-release valproate.

We treated three boys with attention deficit/hyperactivity disorder (ADHD) associated with giant somatosensory evoked potentials (SEP). All responded well to extended-release valproate (EVA), a gamma-aminobutyric acid (GABA) enhancer. Improvement particularly involved hyperactivity and impulsivity. When methylphenidate previously was administered to two patients, symptoms worsened. EVA therefore may be preferable for ADHD with giant SEP.

Adolescent↗

PubMed2006

Magnetic resonance imaging and positron emission tomography findings in status epilepticus following severe hypoglycemia.

We recently experienced a case with asymmetrical cortical abnormality on MRI with focal status epilepticus following severe hypoglycemia. The cerebral blood flow and metabolisms for oxygen and glucose were determined using positron emission tomography (PET) during focal status epilepticus following severe hypoglycemia and at the follow-up period. Prolonged seizure activity produced profound glucose hypermetabolism and mild hyperemia in the region of the presumed cortical focus of epilepsy and in structures anatomically remote from the focus, corresponding to the areas of abnormal signal intensity on the MRI. The patient remained comatose and exhibited a diffuse hypoperfusion/hypometabolism and symmetrical brain atrophy on the follow-up PET and MRI, respectively. Cytotoxic brain edema due to profound glucose metabolism without compensatory increase of the blood flow during status epilepticus may account for the brain abnormality observed on the early MRI. Simultaneous examination of the cerebral blood flow and metabolism using PET can provide useful information about the pathology in patients with status epilepticus.

Aged↗

PubMed2005

Administration of secretin for autism alters dopamine metabolism in the central nervous system.

We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4-6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH(4)) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of 'restricted and repetitive, stereotyped interests and behaviors'). The HVA and BH(4) levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH(4) level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH(4), improving symptoms.

Autistic Disorder↗

PubMed2005

A critical role for sialylation in cryoglobulin activity of murine IgG3 monoclonal antibodies.

Cryoprecipitating IgG3 autoantibodies have been shown to play a significant role in the development of murine lupus-like autoimmune syndrome. However, the structural basis of IgG3 cryoprecipitation still remains to be defined. In view of the implication of positively charged amino acid residues present in variable regions in IgG3 cryoglobulin activity, we explored the role of terminal sialic acids in oligosaccharide side chains for the cryogenic activity of IgG3 mAb. Comparative oligosaccharide structural analysis of different cryogenic and non-cryogenic IgG3 mAb showed an inverse correlation between the extent of sialylation and cryogenic activity. The inhibitory role of sialylation was further confirmed by the demonstration of enrichment of less and more sialylated IgG3 in cryoprecipitated and noncryoprecipitated fractions, respectively, separated from four different cryogenic IgG3 mAb. Significantly, the sialic acid contents of the latter fraction became comparable to those of non-cryogenic IgG3 mAb. Finally, we observed that highly sialylated non-cryogenic IgG3 mAb was more potent in the inhibition of cryoprecipitation of cryogenic IgG3 mAb. Our results thus suggest that the content of negatively charged sialic acids in oligosaccharide side chains is one of the critical factors to determine IgG3 cryoglobulin activity, along with amino acid sequences of the IgG3 variable regions.

Animals↗

PubMed2005

Long-term follow-up of a patient with subacute sclerosing panencephalitis successfully treated with intrathecal interferon alpha.

To clarify long-term effects of intrathecal administration of interferon (IFN)-alpha in subacute sclerosing panencephalitis (SSPE), we followed up a patient with SSPE for 18 years, who had been treated successfully using intrathecal IFN-alpha with response-based dose adjustments. IFN-alpha therapy dramatically induced remission of disease and greatly improved quality of life for 7-8 years, but this was followed by severely deterioration with decorticate posturing and akinetic mutism. Thus, IFN-alpha-induced remission appears most likely to be temporary, even when an SSPE patient shows an excellent initial response. To improve long-term outcome for SSPE patients, more effective therapy is needed.

Adolescent↗

PubMed2005

A case of acute encephalitis with refractory, repetitive partial seizures, presenting autoantibody to glutamate receptor Gluepsilon2.

An 11-year-old male was admitted to our hospital because of high-grade fever, repetitive seizures, and prolonged impairment of consciousness (Glasgow coma scale E1, M5, V1). His seizures were repetitive complex partial seizures that expanded from the unilateral face to the corresponding side of the body. He sometimes developed secondary generalized seizures. While most seizures lasted 1 or 2 min, intractable seizures also frequently (about 5 times/h) occurred. We diagnosed him as encephalitis/encephalopathy, and treated him with artificial respiration, thiamylal sodium, mild hypothermia therapy, steroid pulse therapy, massive gamma-globulin therapy, etc. Afterwards, he had sequelae, such as post-encephalitic epilepsy (same seizures continued to recur), hyperkinesia, impairment of immediate memory, change in character (he became sunny and obstinate), dysgraphia, and mild atrophy of the hippocampus, amygdala, and cerebrum. However, he could still attend a general junior high school. He was diagnosed as acute encephalitis with refractory, repetitive partial seizures (AERRPS). In this case, he was positive for autoantibody to glutamate receptor Gluepsilon2 IgG or IgM in an examination of blood and spinal fluid, and we presumed that this may have influenced his sequelae. In this case, a combination of mild hypothermia therapy, steroid pulse therapy, and massive gamma-globulin therapy was effective.

Autoantibodies↗

PubMed2005

Findings of brain 99mTc-ECD SPECT in high-functioning autism--3-dimensional stereotactic ROI template analysis of brain SPECT.

The aim of this study is confirmation of an abnormal regional cerebral blood flow (rCBF) pattern in high-functioning autism (HFA). Confirmation of an abnormal rCBF pattern in HFA may be useful for elucidate of its pathophysiology and a differential diagnosis, such as with attention-deficit/hyperactivity disorder (AD/HD). Brain 99mTc-ECD SPECT was performed in 16 cases of HFA. The HFA group consisted of 16 cases of HFA. They were all male, with an IQ of 76-126. They had normal brain MRI findings, and had an age of 9-14 years. We examined abnormal rCBF in HFA by comparing the results to those in the control group. The control group consisted of 1 male and 4 females cryptogenic epilepsy patients with normal intelligence. They have no problems in learning at school or mental or behavioral traits. They had normal brain MRI or SPECT findings, and had an age of 7-15 years. 3-dimensional stereotactic ROI template (3DSRT) was used to analyze SPECT data. We calculated the 'relative rCBF (%)' (RI count of each segment x 100/Sum of RI count of the corresponding hemisphere), and compared the values between the two groups. We found a significantly low 'relative rCBF (%)' in the left temporal region in the HFA group. We also calculated the 'L/R ratio' (the 'relative rCBF (%)' of a segment on the left side / the 'relative rCBF (%)' of the corresponding segment on the right side), and compared the value for each segment between the two groups. There were no significant differences in any segments between the two groups. We also checked for differences in the 'relative rCBF (%)' between segments on the right side and corresponding segments on the left side in both the HFA and control groups. We found significant right < left perfusion in the angular region and significant left < right perfusion in the pericallosal, thalamus, and hippocampus region in the HFA group. We also found significant right < left perfusion in the temporal region in the control group. Significant hypoperfusion in the left temporal region due to an unidentified underlying brain pathology and abnormal laterality in the angular, temporal (lack of right < left perfusion), pericallosal, thalamus, and hippocampus regions may influence the symptoms of autism.

Adolescent↗

PubMed2005

Parietal lipomeningocele--case report.

A 2-month-old female infant had had a parietal mass since birth. Neuroimaging revealed a lipoma under the splenium of the corpus callosum that was connected to the subcutaneous lipoma via a bone defect in the cranium bifidum of the parietal region. At the age of 5 months, partial resection of only the extracranial mass was carried out. The histological diagnosis was lipoma. She grew up normally without neurological disorders during follow up for 12 years after the surgery. In the present case, the intracranial lipoma was associated with the cranium bifidum, and dysraphism was possibly involved in the pathogenesis. Resection of only the extracranial subcutaneous tumor can be performed for cosmetic reasons.

Brain Neoplasms↗

PubMed2005

Improvement of cerebral arterial stenosis associated with Basedow's disease. Case report.

A 29-year-old female presented with Basedow's disease manifesting as sudden vomiting, diarrhea, fever over 38 degrees C, transient aphasia, and numbness in her extremities. These symptoms were considered due to cerebral ischemia at a local clinic. Magnetic resonance angiography indicated stenosis of the bilateral distal internal carotid arteries and the bilateral proximal anterior cerebral and middle cerebral arteries. Thyroid swelling and exophthalmos were observed. She was transferred to our hospital. Endocrine function tests showed hyperthyroidism. The diagnosis was Basedow's disease. Her symptoms disappeared after receiving intravenous drip infusion of fluid replacement, and antithyroid and antiplatelet medication. After she became euthyroid, cerebral angiography and magnetic resonance angiography revealed improvement of the stenosis of the cerebral arteries. Stenosis of the terminal portion of the internal carotid artery associated with Basedow's disease is extremely rare. Conservative treatment mainly including antithyroid medications for Basedow's disease, and antiplatelet drugs and intravenous replacement fluid for the ischemic manifestations should be the first choice of treatment unless immediate vascular reconstruction is necessary.

Adult↗

PubMed2005

Mechanical thrombolysis for treatment of acute sinus thrombosis--case report.

A 55-year-old woman presented with consciousness disorders. Computed tomography revealed hemorrhage in the left temporoparietal region. The angiographic diagnosis was progressive sinus thrombosis from the superior sagittal sinus to the bilateral transverse sinuses. Her condition deteriorated despite heparin administration. Therefore, mechanical thrombolysis was performed for sinus thrombosis using a balloon catheter, in addition to supportive thrombolytic therapy with urokinase, resulting in sinus patency. Mechanical thrombolysis is an effective therapeutic modality for sinus thrombosis refractory to heparin administration.

Catheterization↗

PubMed2005

[High functioning pervasive developmental disorder: coexistence with other clinical disorders].

We examined 50 children in high functioning pervasive developmental disorder (HFPDD) to study the comorbidity with other clinical disorders by questionnaires. Seventy-two percentage of them met the criteria for attention deficit hyperactivity disorder (AD/HD). The majority of the children had intelligence quotient less than 90. Learning problems, motor control problems, abnormal responses to sensory stimuli and anxiety disorder frequently coexisted in the children. Since clinical symptoms of HFPDD so diverse, it is possible that some children with HFPDD may be overlooked and diagnosed as having its coexisting disorders.

Adolescent↗

PubMed2004

Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse.

The sphingolipid activator proteins (saposins A, B, C and D) are small homologous glycoproteins that are encoded by a single gene in tandem within a large precursor protein (prosaposin) and are required for in vivo degradation of some sphingolipids with relatively short carbohydrate chains. Human patients with prosaposin or specific saposin B or C deficiency are known, and prosaposin- and saposin A-deficient mouse lines have been generated. Experimental evidence suggests that saposin D may be a lysosomal acid ceramidase activator. However, no specific saposin D deficiency state is known in any mammalian species. We have generated a specific saposin D(-/-) mouse by introducing a mutation (C509S) into the saposin D domain of the mouse prosaposin gene. Saposin D(-/-) mice developed progressive polyuria at around 2 months and ataxia at around 4 months. Pathologically, the kidney of saposin D(-/-) mice showed renal tubular degeneration and eventual hydronephrosis. In the nervous system, progressive and selective loss of the cerebellar Purkinje cells in a striped pattern was conspicuous, and almost all Purkinje cells disappeared by 12 months. Biochemically, ceramides, particularly those containing hydroxy fatty acids accumulated in the kidney and the brain, most prominently in the cerebellum. These results not only indicate the role of saposin D in in vivo ceramide metabolism, but also suggest possible cytotoxicity of ceramide underlying the cerebellar Purkinje cell and renal tubular cell degeneration.

Animals↗

PubMed2004

Transforming growth factor-beta1 stimulates collagen matrix remodeling through increased adhesive and contractive potential by human renal fibroblasts.

Renal tubulointerstitial fibrosis is the common final pathway leading to end-stage renal failure. Tubulointerstitial fibrosis is characterized by fibroblast proliferation and excessive matrix accumulation. Transforming growth factor-beta1 (TGF-beta1) has been implicated in the development of renal fibrosis accompanied by alpha-smooth muscle actin (alpha-SMA) expression in renal fibroblasts. To investigate the molecular and cellular mechanisms involved in tubulointerstitial fibrosis, we examined the effect of TGF-beta1 on collagen type I (collagen) gel contraction, an in vitro model of scar collagen remodeling. TGF-beta1 enhanced collagen gel contraction by human renal fibroblasts in a dose- and time-dependent manner. Function-blocking anti-alpha1 or anti-alpha2 integrin subunit antibodies significantly suppressed TGF-beta1-stimulated collagen gel contraction. Scanning electron microscopy showed that TGF-beta1 enhanced the formation of the collagen fibrils by cell attachment to collagen via alpha1beta1 and alpha2beta1 integrins. Flow cytometry and cell adhesion analyses revealed that the stimulation of renal fibroblasts with TGF-beta1 enhanced cell adhesion to collagen via the increased expression of alpha1 and alpha2 integrin subunits within collagen gels. Fibroblast migration to collagen was not up-regulated by TGF-beta1. Furthermore, TGF-beta1 increased the expression of a putative contractile protein, alpha-SMA, by human renal fibroblasts in collagen gels. These results suggest that TGF-beta1 stimulates fibroblast-collagen matrix remodeling by increasing both integrin-mediated cell attachment to collagen and alpha-SMA expression, thereby contributing to pathological tubulointerstitial collagen matrix reorganization in renal fibrosis.

Actinin↗

PubMed2004

Genetic background markedly influences vulnerability of the hippocampal neuronal organization in the "twitcher" mouse model of globoid cell leukodystrophy.

The twitcher mouse is well known as a naturally occurring authentic mouse model of human globoid cell leukodystrophy (GLD; Krabbe disease) due to genetic deficiency of lysosomal galactosylceramidase. The twitcher mice used most commonly are on the C57BL/6J background. We generated twitcher mice that were on the mixed background of C57BL/6J and 129SvEv, the standard strain for production of targeted mutations. Twitcher mice on the mixed background were smaller and had a shorter lifespan than were those on the C57BL/6J background. Many twitcher mice on the mixed background developed generalized seizures around 30 days that were never seen in twitcher mice on the C57BL/6J background. Neuropathologically, although the degree of the typical demyelination with infiltration of macrophages was similar in the central and peripheral nervous systems, in both strains, marked neuronal cell death was observed only in twitcher mice on the mixed background. In the hippocampus, the neuronal cell death occurred prominently in the CA3 region in contrast to the relatively well-preserved CA1 and CA2 areas. This neuropathology has never been seen in twitcher mice on the C57BL/6J background. Biochemically, the brain of twitcher mice on the mixed background showed much greater accumulation of lactosylceramide. Genetic background must be carefully taken into consideration when phenotype of mutant mice is evaluated, particularly because most targeted mutants are initially on a mixed genetic background and gradually moved to a pure background. These findings also suggest an intriguing possibility of important function of some sphingolipids in the hippocampal neuronal organization and maintenance.

Animals↗