Search PubMed⌕ Search

Biomedical subjects

T Fukazawa

Publications and source records attributed to T Fukazawa.

At least 73 records · Page 4Linked to original sources
PubMed1997

Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis: a new entity?

We studied a dominant hereditary disorder showing progressive spastic paraparesis. The symptoms began in early childhood, with cerebellar deficits and mild mental deterioration, and the subsequent appearance of limb spasticity resulted in severe disability in the 3rd-4th decades of life. None of the patients were associated with any somatic abnormalities. Brain MRI showed diffuse white-matter involvement in all affected patients, but not in unaffected siblings. Although dominant, recessive, or X-linked leukodystrophies cause similar clinical features, our family did not show any known biochemical or gene deficits characteristic of these disorders. The clinical, radiological, and biochemical findings of this family are reported and suggest a possible novel genetic disorder.

Adult↗
PubMed1997

Anti-nuclear antibodies and the optic-spinal form of multiple sclerosis.

We found anti-nuclear antibodies (ANA) (1:20 or higher) in sera from 11 of 16 patients with a diagnosis of the optic-spinal form of multiple sclerosis (OpS-MS) and 13 of 59 patients with other forms of MS (other MS), both rates being significant (P = 0.0004). Six of the OpS-MS patients had a high level of ANA (1:80 or higher), while levels were high in only three of the other MS patients, showing a significant difference (P = 0.0022). Titres of ANA were significantly higher in OpS-MS patients than in other MS patients (P < 0.0001). There was no relationship between the presence of ANA and age in OpS-MS patients, while patients with were older than those without high ANA levels among other MS patients. ANA-positive rate and titres were significantly higher in OpS-MS patients than in sex- and age-matched other MS patients. These results support the concept that OpS-MS constitutes a distinct subgroup among patients with a clinical diagnosis of MS and may indicate that systemic dysregulation of the inflammatory or immune response is more common in OpS-MS patients; the possible pathogenetic relevance of ANA-associated vasculopathy to some patients with a clinical diagnosis of OpS-MS should be considered.

Adult↗
PubMed1997

Facial palsy in multiple sclerosis.

Facial palsy occurred in 21 (19.6%) of 107 Japanese patients with multiple sclerosis (MS) during a mean follow-up period of 4.3 years. We observed residual signs of facial palsy in five other patients in whom acute onset was confirmed from medical records. Facial palsy began on average 7.6 years after the onset of MS but in five patients (4.7%) was the first symptom of MS, preceding the next MS symptom by 0.5-3 years. Facial palsy was usually associated with other brainstem signs, while two patients showed only facial palsy 1 and 3 years after the onset of MS. Twenty-one (84.0%) of the 25 patients who underwent brain magnetic resonance imaging (MRI) showed brainstem lesions in the pontine tegmentum ipsilateral to the facial palsy. However, the two patients without other symptoms or signs had no apparent causal lesion on MRI, which suggests difficulty in differentiating idiopathic Bell's palsy from MS- associated facial palsy by MRI, although it has an excellent capacity to detect causal lesions of facial palsy associated with MS.

Adult↗
PubMed1997

Coordinated change between complement C1s production and chondrocyte differentiation in vitro.

In vitro synthesis of the first component of complement C1s was examined by using hamster epiphyseal chondrocytes (HAC) and human chondrosarcoma cell line HCS-2/8. Hamster and human C1s produced by the cells were quantified by immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA), respectively. It was possible to measure active and inactive C1s by sandwich ELISA, when we used anti-human C1s monoclonal antibodies, M241 recognizing only active C1s, and M365 and M81 recognizing both active and inactive C1s. Approximately 40% of C1s secreted from HCS-2/8 was found to be activated in the culture medium, whereas C1s from HAC was not. C1s production increased in accordance with chondrocyte differentiation induced by ascorbic acid. In contrast, transforming growth factor-beta1 and basic fibroblast growth factor, which inhibited differentiation, suppressed C1s production. These results confirmed our previous observation showing that C1s synthesis increased with differentiation into hypertrophic chondrocytes in vivo.

Amino Acid Sequence↗
PubMed1997

Congenital right diaphragmatic hernias through posterolateral and anterolateral defects associated with extralobar pulmonary sequestration: a case report.

Multiple diaphragmatic hernias in the unilateral diaphragm are extremely rare. The authors report a neonate with diaphragmatic hernias through two defects in the right diaphragm: a posterolateral defect without a hernia sac and an anterolateral defect with one. After excision of the anterolateral hernia sac, each defect was closed. Histology studies showed extralobar pulmonary sequestration in the removed hernia sac. The presence of sequestrated pulmonary tissue indicates the possibility of interference with the closure of the pleuroperitoneal canal and muscularization in the diaphragm, which may result in multiple defects.

Bronchopulmonary Sequestration↗
PubMed1997

A model of cochlear micromechanics.

A cochlear model is presented which has two degrees of freedom, the motion of the basilar membrane and that of the tectorial membrane (TM), in every cross section of the organ of Corti. It assumes that the reticular lamina is virtually rigid, so that the apical portion of the outer hair cells is firmly anchored to it, and also that the TM is directly driven by the BM through the marginal net of the TM, which anchor to the phalanges of the outermost row of Deiters' cells or Hensen's cells, or both. It is shown that the model can produce more than 40 dB of cochlear gain in the frequency-domain simulation and 30 dB in time-domain simulation. Transiently evoked otoacoustic emissions and cochlear microphonics are simulated in the time domain.

Acoustic Stimulation↗
PubMed1997

Removal of human immunodeficiency virus type 1 (HIV-1) protease inhibitors from preparations of immature HIV-1 virions does not result in an increase in infectivity or the appearance of mature morphology.

The processing of gag and gag-pol polyproteins by human immunodeficiency virus type 1 (HIV-1) protease is a crucial step in the formation of infectious HIV-1 virions. In this study, we examine whether particles produced in the presence of inhibitors of HIV-1 protease can subsequently undergo gag polyprotein cleavage with restoration of infectivity following removal of the inhibitors. Viral particles produced during 7 days of culture in the presence of the protease inhibitors KNI-272 (10 microM) and saquinavir (5 microM) contained predominantly p55gag polyprotein but little or no p24gag cleavage product. Following resuspension of the particles in medium free of the inhibitor, some gag polyprotein processing was detected in particles produced from the KNI-272-treated cells, but not from the saquinavir-treated cells within the first 3 h. However, the majority of the protein remained as p55gag throughout a 48-h experimental period. The infectivity (50% tissue culture infective dose per milliliter) of the viral particles from KNI-272-treated cells was 10(6)-fold lower than that of control particles and did not significantly increase over the 48 h after the inhibitor was removed, despite the apparent return of protease function in a subset of these virions. This failure to restore infectivity was due neither to a reduction in the number of particles produced by protease inhibitor-treated cells nor to a failure of HIV RNA to be packaged in the virions. These particles also failed to express the mature phenotype by electron microscopy. Thus, while some processing of the gag polyprotein can occur in isolated HIV virions, this does not appear to be sufficient to restore infectivity in the majority of particles. This finding suggests that there may be constraints on postbudding polyprotein processing in the production of viable particles. These results should have positive implications regarding the use of protease inhibitors as anti-HIV drugs.

Blotting, Western↗
PubMed1997

Spinocerebellar ataxia type 1 and familial spontaneous pneumothorax.

We report two siblings with spinocerebellar ataxia type 1 (SCA1) who experienced frequent episodes of spontaneous pneumothorax. Radiologic findings indicated underlying degenerative changes in the lungs. This suggests a possible pathophysiologic relationship between SCA1 and familial occurrence of spontaneous pneumothorax.

Adult↗
PubMed1997

[Progressive supranuclear palsy with macular degeneration--report of three cases].

Three cases of progressive supranuclear palsy (PSP) with decreased visual acuity were reported. Case 1 was a 50-year-old man, case 2 a 60-year old woman, and case 3 a 66-year-old woman. They all had vertical gaze palsy and unexplained falls, and were diagnosed as PSP by NINDS-SPSP clinical criteria. All cases had symptoms of difficulty in vision; therefore, detailed ophthalmological tests were performed. Ophthalmoscopic findings of macula revealed atrophy in case 1 and 2, and brownish discoloration in case 3. Fluorescein fundus angiography done in case 1 showed abnormal staining at the macula. Multifocal electroretinography performed in case 3 showed absence of big response in the macula. These results indicated macular degeneration. None of three cases had cataract. And visual evoked potentials of case 2 and 3 showed prolonged P100 latency. From these results, we suspected that decreased visual acuity of our cases were due to macular degeneration and difficulty to catch the object at the fovea because of gaze palsy. There had been no reports of macular degeneration with PSP, but we might have overlooked these findings, because of dementia, gaze palsy, and apraxia of lid opening. The possibility of macular degeneration is raised as a part of neurological signs is PSP.

Aged↗
PubMed1996

Tyrosine phosphorylation of Cbl upon epidermal growth factor (EGF) stimulation and its association with EGF receptor and downstream signaling proteins.

We and others have shown that Cbl, the protein product of the c-cbl proto-oncogene, is an early target of tyrosine phosphorylation upon stimulation through the immune cell surface receptors, which signal through noncovalently associated cytoplasmic tyrosine kinases. Using human mammary epithelial cells that express a natural epidermal growth factor (EGF) receptor and require EGF as an essential growth factor, we demonstrate here that Cbl is a prominent target of tyrosine phosphorylation upon stimulation through the EGF receptor tyrosine kinase. Phosphorylation of Cbl was EGF dose-dependent, rapid (detectable as early as 5 s and maximal by 2 min), and relatively sustained (detectable even after 1 h). Co-immunoprecipitation studies demonstrated that Cbl became associated with the EGF receptor in an EGF-dependent manner. Cbl was basally associated with the adaptor protein growth factor receptor-binding protein 2 (Grb2), and this interaction was further enhanced by EGF stimulation; however, the interaction was entirely mediated via the Grb2 Src homology 3 (SH3) domains, suggesting that binding of Grb2 SH2 domain to EGF receptor provides one mechanism of Cbl's association with the EGF receptor. EGF stimulation also induced the association of Cbl with Src homology and collagen (Shc) protein, p85 subunit of the phosphatidylinositol 3-kinase and Crk proteins, in particular with the CrkL isoform. Interactions of Cbl with the EGF receptor and multiple downstream signaling proteins suggest a role for this proto-oncogene product in mitogenic signaling through growth factor receptor kinases.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Stimulation through the T cell receptor induces Cbl association with Crk proteins and the guanine nucleotide exchange protein C3G.

We and others have recently identified Cbl, the protein product of the c-cbl protooncogene, as an early tyrosine kinase substrate upon T cell activation and have shown that Cbl forms in vivo complexes with Src family tyrosine kinases, Grb2 adaptor protein, and the p85 subunit of PI-3 kinase. Here we show that Cbl associates with all three forms of the human Crk protein, predominantly CrkL, following T cell receptor activation of Jurkat T cells. Association between Cbl and Crk proteins was confirmed in normal human peripheral blood-derived T cells. In vitro, Cbl was able to interact with the Crk SH2 domain but not the SH3 domain. A phosphopeptide corresponding to a potential Crk SH2 domain-binding motif in Cbl (pYDVP) specifically inhibited binding between Cbl and Crk SH2 domain. Anti-Cbl antibody completely immunodepleted the CrkL-associated 120kDa phosphotyrosyl polypeptide, suggesting that the recently described p130cas-related Crk-associated p116 of T cells may be Cbl. Consistent with this possibility, the 4F4 antibody used to characterize the p116 polypeptide cross-reacted with Cbl protein when it was resolved on one- or two-dimensional gels. CrkL was constitutively associated with a substantial amount of the guanine nucleotide exchange protein C3G, and a fraction of the C3G protein was coimmunoprecipitated with Cbl in activated Jurkat T cells. These results suggest the possibility that Cbl may participate in a signaling pathway that regulates guanine nucleotide exchange on small G-proteins in T cells.

Adaptor Proteins, Signal Transducing↗
PubMed1996

p120cbl is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase.

We and others have demonstrated that the c-cbl proto-oncogene product is one of the earliest targets of tyrosine phosphorylation upon T cell receptor stimulation. Given the similarities in the B and T lymphocyte antigen receptors, and the induction of pre-B leukemias in mice by the v-cbl oncogene, we examined the potential involvement of Cbl in B cell receptor signaling. We demonstrate prominent and early tyrosine phosphorylation of Cbl upon stimulation of human B cell lines through surface IgM. Cbl was associated in vivo with Fyn and, to a lesser extent, other Src family kinases. B cell activation also induced a prominent association of Cbl with Syk tyrosine kinase. A substantial fraction of Cbl was constitutively associated with Grb2 and this interaction was mediated by Grb2 SH3 domains. Tyrosine-phosphorylated Shc, which prominently associated with Grb2, was detected in association with Cbl in activated B cells. Thus, Grb2 and Shc adaptors, which associate with immunoreceptor tyrosine based activation motifs, may link Cbl to the B cell receptor. B cell activation also induced a prominent association between Cbl and the p85 subunit of phosphatidylinositol (PI) 3-kinase resulting in the association of a substantial fraction of PI 3-kinase activity with Cbl. Thus, Cbl is likely to play an important role to couple the B cell receptor to the PI 3-kinase pathway. Our results strongly suggest a role for p120cbl in signaling downstream of the B cell receptor and support the idea that Cbl participates in a general signal transduction function downstream of the immune cell surface receptors.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Spontaneous otoacoustic emissions in an active feed-forward model of the cochlea.

Numerical simulation of spontaneous otoacoustic emissions (SOAE) was done using a 1-dimensional macromechanical cochlear model with an active 'feed-forward' force in every section of the basilar membrane (BM). When the activity of the force was increased the model showed more stability than a 'feed-back' model and could have excitation curves with larger tips without divergence of the solution. The stability broke up when either (1) the damping of the BM was made slightly irregular throughout the BM or (2) the feed-forward force was switched off at a certain part of the BM, and limit cycle oscillations (LCO) emerged within the cochlea. Critical feed-forward value for the emergence of LCO in the first setting of BM (1), which was intended to simulate physiological variations in the distribution of outer hair cells, was searched utilizing the 'ringing' of delayed evoked otoacoustic emissions (DEOAE). In the course of the search, smooth transition from a DEOAE to a set of SOAEs was found to occur keeping the same spectral fine structure of the emissions when the feed-forward force surpassed a certain value. It was, as a result suggested that the two kinds of emissions may have the same origin. In the second setting of BM (2), which was intended to simulate pathological cases. LCOs tended to be stronger than in the first one and they had similarity not only to real SOAEs but also to tinnitus in the way they showed up very close to or at the "edge' of the switched-off part of the BM.

Auditory Threshold↗
PubMed1996

Central phenotype and related varieties of spinocerebellar ataxia 2 (SCA2): a clinical and genetic study with a pedigree in the Japanese.

The gene for SCA2 has been mapped to chromosome 12q23-q24.1, but the mutant gene remained to be identified. When studying a Japanese family with SCA2, we noted that clinical features and disability varied among patients, with the central feature being progressive ataxia-slow eye movement-hyporeflexia syndrome. Additional symptoms were parkinsonism with minor cerebellar deficits, and severe ataxia with choreoathetosis. Our experience plus related literature documentation indicates that choreoathetosis is not so rare at the advanced stage of the disease, with onset at an early age, and that the variety of SCA2 phenotype depends on age at onset and duration of the disorder.

Adult↗
PubMed1996

Serum carnitine and disabling fatigue in multiple sclerosis.

The serum concentrations of total, free and acylcarnitine were compared in 25 patients with multiple sclerosis (MS) and among age- and sex-matched normal controls by the new enzymatic cycling method in order to clarify whether the fatigue in MS might be due to possible carnitine-related fatty acid metabolic abnormalities in the mitochondria of skeletal muscles. Patients with MS were divided into those with and those without excessive fatigue. Levels of total and free carnitine were not significantly different between MS patients and normal controls. Levels of acylcarnitine, whose decrease in chronic fatigue syndrome has been reported, were also similar between MS patients and normal controls. There was no difference in these carnitine levels between MS patients with and without excessive fatigue. We argue that acylcarnitine deficiency and fatty acid metabolic dysfunction in mitochondria are not relevant to the excessive fatigue in patients with MS, and further explanatory investigations are to be sought.

Adult↗
PubMed1996

Clinical features and natural history of spinocerebellar ataxia type 1.

SCA1 is a dominant spinocerebellar ataxia (SCA) and a multi-systemic syndrome caused by abnormal expansion of unstable CAG repeat in a novel gene located on chromosome 6p22-p23. We clinically studied 35 Japanese SCA1 patients who were assumed to have come from a common origin. The age at onset ranged from 15-63 years, and significantly correlated with CAG repeat units of mutant alleles. Ataxia was the initial symptom, and the majority of patients had a similar history of signs and symptoms. Nystagmus was at first minimal, later attenuated, and a slow saccade followed. Limb tendon reflexes were mostly hyperactive and depressed with the development of diffuse amyotrophy. The cardinal feature was ataxia-hyperreflexia-late slow saccade syndrome with terminal amyotrophy. Although the phenotype of SCA1 overlaps with those of other dominant SCAs, some facets of the neurological events differ from either SCA2 with ataxia-hyporeflexia-slow saccade syndrome, or early-onset Machado-Joseph disease with dystonia-bradykinesia-spasticity syndrome.

Adolescent↗