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Biomedical subjects

J Kira

Publications and source records attributed to J Kira.

At least 127 records · Page 7Linked to original sources
PubMed1998

Expression and processing of recombinant human galactosylceramidase.

Stable transformants of CHO cells that overexpress human galactosylceramidase (GALC) were established. The GALC within the cell consisted of 50- and 30-kDa proteins. The active GALC secreted into the culture medium in large amounts consisted of the 80-kDa precursor enzyme. We confirmed that the precursor enzyme was taken up by fibroblasts via the mannose-6-phosphate receptor and processed into the 50- and 30-kDa fragments. Fragmentation was inhibited by the lysosomotropic agents chloroquine and NH4Cl, suggesting that it occurs within the lysosome. GALC mutations identified in globoid cell leukodystrophy suppressed fragmentation. Neither the 50- or 30-kDa fragment expressed had GALC activity, indicative that the entire structure is necessary for enzyme activity and that fragments expressed separately cannot associate to form the active enzyme.

Animals↗
PubMed1998

Multiple sclerosis with mite antigen-specific IgE.

The total and mite antigen-specific IgE in the sera were measured in 60 patients with multiple sclerosis (MS) and 40 healthy controls by an enzyme-linked immunosorbent assay using two common mite antigens, Dermatophagoides farinae and Dermatophagoides pteronyssinus, in order to study the role of atopy in MS. Neither the total IgE level nor the frequency of mite antigen-specific IgE differed significantly between the MS patients (mean total IgE 162 U/ml, 42% mite IgE-positive) and healthy controls (mean total IgE 168 U/ml, 35% mite IgE-positive). The MS patients with mite antigen-specific IgE showed a significantly higher level of serum total IgE (mean 293 U/ml, P=0.0005) and a higher frequency of atopic disorders (36%, P=0.0508) than did the MS patients without mite antigen-specific IgE (mean total IgE 68 U/ml, atopic disorders 14%). The former group also showed a significantly higher frequency of male (P=0.0216), a younger age of onset (P=0.0081), a lower expanded disability status scale (EDSS) score (P=0.03) and a lower protein content in the cerebrospinal fluid (CSF) (P=0.0426) than the latter, while the duration of disease and a number of relapses did not differ significantly between the two groups. In addition, the mite IgE-positive MS showed a very low frequency of oligoclonal IgG bands in CSF (4%) and a significantly higher association of HLA-A24 (87.5%) than the healthy controls (45%). Therefore, the presence of IgE response to the mite antigens and atopy appeared to significantly lessen the severity of the disease and the immunologic abnormalities in MS.

Adult↗
PubMed1998

Two CPT2 mutations in three Japanese patients with carnitine palmitoyltransferase II deficiency: functional analysis and association with polymorphic haplotypes and two clinical phenotypes.

Carnitine palmitoyltransferase II (CPT II) deficiency manifests as two different clinical phenotypes: a muscular form and a hepatic form. We have investigated three nonconsanguineous Japanese patients with CPT II deficiency. Molecular analysis revealed two missense mutations, a glutamate (174)-to-lysine substitution (E174K) and a phenylalanine (383)-to-tyrosine substitution (F383Y) in the CPT II cDNA. Transfection experiments in COS-1 cells demonstrated that the two mutations markedly decreased the catalytic activity of mutant CPT II. Case 1 (hepatic form) was homozygous for the F383Y mutation, whereas case 3 (muscular form) was homozygous for the E174K mutation. Case 2 and her brother, who were compound heterozygotes for E174K and F383Y, exhibited the hepatic phenotype. We also identified a novel polymorphism in the CPT2 gene, a phenylalanine (352)-to-cysteine substitution (F352C), which did not alter CPT II activity in transfected cells. It was present in 21 out of 100 normal alleles in the Japanese population, but absent in Caucasian populations. Genotyping with the F352C polymorphism and the two previously reported polymorphisms, V368I and M647V, allowed normal Japanese alleles to be classified into five haplotypes. In all three families with CPT II deficiency, the E174K mutation resided only on the F1V1M1 allele, whereas the F383Y mutation was observed on the F2V2M1 allele, suggesting a single origin for each mutation.

Adult↗
PubMed1998

Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid: diagnostic value for progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease in the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). PML affects individuals with decreased immune competence and is now one of the common opportunistic infections in patients with AIDS. JCV DNAs in the brain of PML patients contain various PML-type regulatory regions that were generated from the archetypal regulatory region during persistence. Recently, many studies have suggested that detection of JCV DNA from the cerebrospinal fluid (CSF) may offer a tool for diagnosing PML. However, in all of these studies, coding sequences within the T antigen or capsid protein gene have been targeted for amplification. To amplify the JCV regulatory region, we established a nested PCR that could efficiently amplify the regulatory region from most JCV subtypes prevalent in the world. Using this PCR, we amplified JCV regulatory regions from the CSF samples from 4 patients strongly suspected of PML, whereas amplification was negative from 80 CSF samples from patients without PML. Sequencing of the amplified fragments revealed that they had unique deletions and/or duplications. Furthermore, in 3 PML patients, we analyzed the structures of regulatory regions derived from the brain as well as CSF. In each of these cases, the major regulatory sequence of both origins were identical. This finding indicates that JCV DNA in brain lesions is excreted in the CSF. Since the structures of PML-type JCV regulatory regions are unique to individual patients, the current PCR, if the amplified fragments are sequenced, can eliminate false positives that may arise from contaminations.

Brain↗
PubMed1998

HLA-DP-associated susceptibility to the optico-spinal form of multiple sclerosis in the Japanese.

We studied polymorphism of the HLA-DP gene in 46 patients with optico-spinal form (Asian type) multiple sclerosis (MS) showing recurrent opticomyelitis and 46 patients with Western type MS with disseminated central nervous system involvement. We previously reported a significant association between an HLA-DRB1 *1501-DRB5*0101 haplotype and susceptibility to Western type but not Asian type MS. In the present study, we found that the frequencies of DPA1 *0202 and DPB1 *0501 alleles were significantly increased in patients with Asian type MS, as compared with findings in 92 healthy control subjects (91.3% vs 65.2%, P(corr)<0.05 and 89.1% vs 63.0%, P(corr)<0.05 respectively), but not in Western type MS. Our data provide further evidence that Asian and Western type MS are distinct regarding the immunogenetic background.

Alleles↗
PubMed1998

Molecular analysis of HLA class I (HLA-A and -B) and HLA class II (HLA-DRB1) genes in Japanese patients with multiple sclerosis (Western type and Asian type).

The types of HLA-A, -B and -DRB1 genes were studied in 146 Japanese patients with multiple sclerosis (MS) using polymerase chain reaction-sequence-specific oligonucleotide probe analysis. Fifty-seven patients who displayed selective clinical involvement of the optic nerve and spinal cord were classified as having Asian type MS. The other 89 patients had disseminated central nervous system involvement and were classified as having Western type MS. The frequency of HLA-B*5101 was increased in both types of MS patients compared with controls. The frequency of HLA-DRB1*1501 was increased in Western type MS and the frequency of HLA-DRB1*0802 was increased in Asian type MS compared to controls. After correction of P values, the association of Western type MS patients with HLA-DRB1*1501 was statistically significant (Pc=0.0003) whereas other HLA alleles showed no significant association. These results suggest that HLA class I (HLA-A and -B) alleles may not contribute to a strong susceptibility to MS in Japanese compared to HLA class II (HLA-DRB1) alleles.

Alleles↗
PubMed1998

Acute myelitis with hyperIgEaemia and mite antigen specific IgE: atopic myelitis.

An occurrence of acute localised myelitis was recently seen in four adult patients with atopic dermatitis who had hyperIgEaemia and mite antigen specific IgE. The total and mite antigen specific IgE was therefore studied in serum samples from 19 consecutive patients with acute localised myelitis of unknown aetiology, 56 patients with clinically definite multiple sclerosis, and 40 healthy controls. The total IgE concentration was significantly higher in acute localised myelitis (median=360 U/ml) than in multiple sclerosis (median=52 U/ml, p<0.0001) and the controls (median=85 U/ml, p=0.0002). The specific IgE to Dermatophagoides pteronyssinus was found more often in patients with acute localised myelitis (95%) than in patients with multiple sclerosis (34%, p<0.0001) and the controls (35%, p<0.0001) and the specific IgE to Dermatophagoides farinae was similar (acute localised myelitis 79%, multiple sclerosis 29% (p<0.0001), controls 30%, (p=0.0003). Atopic dermatitis coexisted more commonly in patients with acute localised myelitis (37%) than in patients with multiple sclerosis (0%, p<0.0001) and the controls (7.5%, p=0.0089). Therefore, acute localised myelitis with hyperIgEaemia, in which atopy to mite antigens seems to exist, may be a distinct subtype of allergic myelitis-that is, atopic myelitis.

Adult↗
PubMed1998

A novel mutation of the GTP-cyclohydrolase I gene in a patient with hereditary progressive dystonia/dopa-responsive dystonia.

We report a 37-year-old Japanese woman with hereditary progressive dystonia with marked diurnal fluctuation and dopa-responsive dystonia. She developed dystonia in the lower limbs at the age of 11 years, followed by spasmodic torticollis and resting tremor of the feet, which responded remarkably to low doses of levodopa (100 mg/day). Concentrations of biopterin and neopterin in CSF were decreased. Polymerase chain reaction analysis of the guanosine 5'-triphosphate cyclohydrolase I gene revealed a novel mutation (Thr186-->Lys).

Adult↗
PubMed1998

Peptide-based molecular analyses of HLA class II-associated susceptibility to autoimmune diseases.

Recent advances in knowledge of crystal structures of MHC class II molecules has advanced understanding of the molecular basis for interactions between peptides and HLA class II molecules. Polymorphism of HLA class II molecules influences structures of peptides bound to HLA class II molecules. To better understand mechanisms related to particular HLA class II alleles and autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative autoreactive T cells. Autoimmune diseases occur in Caucasians, Blacks and Asians, albeit with a different incidence. In some autoimmune diseases, disease-susceptible HLA class II alleles are closely related but different, and clinical manifestations of diseases differ among ethnic groups. These phenomena strongly suggest that difference in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may explain the different clinical manifestations of diseases. Therefore, a comparison among disease-susceptible HLA class II alleles, autoimmune self-peptides and clinical manifestations of autoimmune diseases in different ethnic groups would be instructive. We directed efforts to determining: (1) HLA-class II alleles specific to Asian populations and which are associated with susceptibility to autoimmune diseases, (2) binding-peptide motifs for these HLA class II molecules, and (3) self-peptides presented by susceptible HLA class II molecules to stimulate autoreactive T cells related to the development of autoimmune diseases in Asians. In this review, our related recent investigations are described and the uniqueness of HLA class II-associated autoimmune diseases in Asians is given emphasis.

Amino Acid Sequence↗
PubMed1998

[An adult case of peripheral facial nerve palsy following acute cerebellitis associated with high antibody titers against varicella-zoster virus].

Here we report a case of acute cerebellitis, in which the patient developed right peripheral facial palsy during the recovery phase of cerebellar ataxia. A 67-year-old man developed truncal and limb ataxia following a fever, general fatigue and anorexia. He was diagnosed to have acute cerebellitis. While the ataxia symptoms were improving without any treatment, right peripheral facial nerve palsy developed and an MRI revealed an enhancement of the right facial nerve proximal to the geniculate ganglion. After treatment with acyclovir and corticosteroids, his facial nerve palsy and ataxia both gradually improved. There has been no previous report of an adult case who developed peripheral facial nerve palsy during the recovery phase of acute cerebellitis. This case indicates that a wide spectrum of neurological complications may develop in association with a varicella-zoster virus infection.

Acute Disease↗
PubMed1998

Subacute multifocal painful neuropathy with spontaneous remission.

We present the cases of two patients with subacute onset of multifocal painful neuropathy with spontaneous remission and no relapse. The distribution of pain in patient 1 was hands (median > ulnar nerve region) and feet (peroneal and terminal tibial nerve regions), and in patient 2, hands (ulnar nerve region) and feet, left worse than in right. Both patients experienced facial numbness. Deep tendon reflexes were intact except for absent ankle jerks in patient 2. Motor nerve conduction studies demonstrated a marked prolongation of the distal motor latencies with normal proximal segment conduction velocities, suggesting distal demyelination. Cerebrospinal fluid protein concentration was elevated in patient 2, but no definite abnormality was found on sural nerve biopsy. A demyelinating neuropathy with a monophasic self-limited course may be consistent with Guillain-Barre syndrome (GBS). However, the multifocal painful sensory symptoms with facial numbness and the marked distal nerve conduction slowing in our cases are not consistent with GBS.

Adult↗
PubMed1998

[A case of cervical radiation radiculopathy resembling motor neuron disease].

A 67-year-old man developed slowly progressive muscular weakness in the bilateral upper extremities (C5- 7 regions) without signs of sensory deficit following the cervical radiation therapy (70.5Gy) for right laryngeal cancer 4 years before. These clinical signs resembled those of lower motor neuron disease. MRI with gadolinium-DTPA, however, showed enhancement in the bilateral C5 and C6 anterior roots, suggesting the cervical radiculopathy due to radiotherapy. It is known that radiation to the spinal cord can lead to "selective anterior horn cell injury". This is the first case report of the cervical radiation radiculopathy, which, if without MRI, might be classified into selective anterior horn cell injury. Suggestion is made for the hypothesis that the spinal motoneuron loss in radiation myelopathy would be caused by retrograde degeneration due to anterior root damages.

Aged↗
PubMed1998

[A case of MELAS showing CSF pleocytosis associated with stroke-like episodes].

A 55-year-old woman, who had two episodes of difficulty in putting a key into a keyhole probably due to optic ataxia at age 52 and 54 years old, developed speaking errors and was admitted to our hospital. She was 152.5 cm in height and 52.5 kg in weight. Neurological examination revealed right homonymous hemianopsia and sensory aphasia. A CSF examination revealed lymphocytic pleocytosis of 88/microliter. Serum lactate and pyruvate were remarkably increased after an aerobic exercise test. A few ragged-red fibers were present in the biopsied brachial biceps muscle. Brain MRI by FLAIR method showed scattered high signal lesions in the left temporal lobe, bilateral parieto-occipital lobes, left insular cortex and left thalamus. The left superficial temporal lesion was enhanced by gadolinium-DTPA. The proton MRS demonstrated the lactic acid peak as well as the decrease of NAA/choline ratio (0.38) in the left parieto-occipital region. Thus, she was diagnosed as a case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and successfully treated with ubidecarenone (150 mg/day). Six months later, she again developed seizure, right hemiparesis and deterioration of aphasia and presented again CSF lymphocytic pleocytoses of 15/microliter. Brain MRI demonstrated new lesions in the left temporoparietal lobes, left insular cortex and left corona radiata. Therefore, CSF pleocytosis appeared to be associated with stroke-like episodes in this case. Although the mechanism of CSF pleocytosis remains to be elucidated, it may involve the breakdown of blood-brain barrier caused by mitochondrial dysfunction. Otherwise, an inflammatory process similar to that in cases of Leber disease, who developed multiple sclerosis-like additional lesions in the central nervous system, may also take place in MELAS.

Cerebrovascular Disorders↗
PubMed1998

[A case of early-onset cortical cerebellar atrophy with rhythmic skeletal myoclonus in the left upper limb].

A 19-year-old man developed progressive unsteady gait and speech disturbance two years ago. He recently noticed muscle twitches in the left limb. Neurological examination revealed scanning speech, saccadic ocular movement, ataxia of trunk and limbs predominant on the left side. Rhythmic myoclonus was present at rest around the left shoulder and arm, and amplified by raising the left arm. There was no myoclonus in the soft palate. MRI revealed only a cerebellar atrophy. This patient was diagnosed as having cortical cerebellar atrophy with rhythmic skeletal myoclonus (RSM). Tc-99m ECD SPECT showed a decrease in the blood flow of the right thalamus when the myoclonus was enhanced by raising the left upper limb, which suggests that the cerebello-thalamo-cortical system as well as Guillain-McIlaret triangle is involved in the development of RSM.

Adult↗
PubMed1997

Induction of chronic inflammatory arthropathy and mesenchymal tumors in rats infected with HTLV-I.

To compare the pathogenicity of HTLV-I derived from patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and that from patients with adult T-cell leukemia (ATL), neonatal WKA rats were inoculated with either an HTLV-I-infected T-cell line (Fuk line) newly established from a HAM/TSP patient or MT-2 derived from a patient with ATL. Of 38 rats, 34 developed mesenchymal tumors (89%) only after 14 months of age, irrespective of the cell lines used. The rats inoculated with the Fuk line developed severe arthritis (27%) and anti-type II collagen antibody (64%), and less frequently, paraparesis (7%). Those inoculated with MT-2 developed paraparesis (23%), but not arthritis. Cyclophosphamide (CY) administration to induce immunosuppression in the Fuk line-inoculated rats increased the frequency of paraparesis (70%), but decreased the frequency of tumors (20%). HTLV-I proviral DNA was found in the spinal cord, sciatic nerves, tumors, and joints, whereas pX mRNA was detected in the sciatic nerves and tumors, but not in the spinal cord and joints. As a result, HTLV-I is considered to facilitate development of both chronic inflammatory arthropathy associated with autoimmunity and mesenchymal tumors in rats by experimental infection, and its pathogenicity is likely to be greatly influenced by the host immune state.

Animals↗
PubMed1997

Acute myelitis associated with hyperIgEemia and atopic dermatitis.

We herein describe 4 adult patients with upper cervical myelitis presenting with paresthesia in the distal parts of all four limbs and who also all had hyperIgEemia. Two of them had full-blown atopic dermatitis at the time of neurologic illness, while the others had a preceding history of atopic dermatitis. All showed high signal intensity lesions at either the C3 or C4 segment, which mainly affected the posterior column on the T2-weighted spinal cord magnetic resonance imaging. All patients had specific IgE antibodies to two mite antigens and their onset of myelitis coincided with the seasonal increase of the mite antigens in Japan. Therefore, it is possible that the atopic conditions with hyperIgEemia in these patients may thus have contributed to the development of myelitis.

Acute Disease↗