PubMed Health⌕ Search

Biomedical subjects

Jun-ichi Kira

Publications and source records attributed to Jun-ichi Kira.

At least 19 recordsLinked to original sources
PubMed2006

Increased IL-13-producing T cells in ALS: positive correlations with disease severity and progression rate.

We measured the intracellular productions of IFNgamma, IL-2, IL-4, IL-13 and TNFalpha in peripheral blood CD4(+) and CD8(+) T cells from 21 amyotrophic lateral sclerosis (ALS) patients, 14 disease controls (DC) with spinocerebellar degeneration and 16 healthy controls (HC). Only the percentages of CD4(+)IL-13(+) and CD8(+)IL-13(+) T cells were significantly higher in ALS patients than in DC and HC. The CD4(+)IL-13(+) T cell percentages showed a significant negative correlation with the revised ALS functional rating scale scores and significant positive correlation with the disease progression rate, suggesting that IL-13 contributes to ALS.

Adult↗
PubMed2006

Intraneuronal amyloid beta42 enhanced by heating but counteracted by formic acid.

Amyloid beta-protein ending at 42 (Abeta42) is the major peptide deposited in Alzheimer's disease (AD) brain. In immunocytochemical studies, formic acid treatment is used to dramatically enhance Abeta immunoreactivity. Recently, Abeta42 has been reported to accumulate in AD neurons. Since heating is known to enhance intracellular protein immunoreactivity, we used an autoclaving protocol to enhance intraneuronal Abeta42 immunoreactivity. Using this protocol, both anti-Abeta42 N-terminal and C-terminal antibodies, but not anti-Abeta40 C-terminal antibody, labeled AD neurons. Moreover, formic acid treatment counteracted such effects of autoclaving. Thus, intraneuronal Abeta42 accumulation may have been underestimated by conventional methods using formic acid only.

Aged↗
PubMed2006

Upregulation of myeloperoxidase in patients with opticospinal multiple sclerosis: positive correlation with disease severity.

To clarify the role of myeloperoxidase (MPO) in multiple sclerosis (MS), we measured serum MPO levels in 86 Japanese patients with relapsing remitting MS, 47 with opticospinal MS (OSMS) and 39 with conventional MS (CMS), and 85 healthy subjects by sandwich enzyme immunoassays and analyzed relationships with clinical features. We found a significant increase in serum MPO in OSMS patients at relapse and remission, and in CMS patients at remission compared with controls. By logistic regression analysis, the clinical variable associated with high level of MPO at remission in OSMS patients (higher than the mean+/-2 S.D. of healthy controls) was only Kurtzke's Expanded Disability Status Scale (EDSS) score in blood sampling (p=0.0245); that is, a greater EDSS scores in the high MPO group, whereas in CMS none were associated. The results of our study suggest that MPO levels in remission are related with severe tissue destruction in OSMS.

Adult↗
PubMed2006

Myeloradiculitis caused by Cryptococcus neoformans infection in a patient with ulcerative colitis: a neuropathological study.

Meningitis is the most common feature of cryptococcal infection of the nervous system. We herein describe the case of a 48-year-old man with fulminant cryptococcal myeloradiculitis, whose initial symptoms were impotence, dysuria and weakness of the lower extremities. He had been administered prednisolone and azathioprine for 7years for ulcerative colitis before onset of myeloradiculitis. He finally developed meningoencephalitis and died 2 months after onset despite treatment with amphotericin B and flucytosine. Post-mortem examination revealed numerous infiltrations of cryptococci in the spinal roots as well as in the meninges and subarachnoid space. Inflammatory cells and cryptococci had infiltrated the vessel walls in the spinal cord, and this was accompanied by necrotizing myelopathy. Myeloradiculitis is rare in cryptococcal infection, and this is the first case report to demonstrate direct cryptococcal infection in the spinal roots. Cryptococcal infection should be considered while managing myeloradiculopathy of unknown etiology, especially in immunocompromised patients.

Colitis, Ulcerative↗
PubMed2006

CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis.

We simultaneously measured 16 cytokines/chemokines in cerebrospinal fluid (CSF) from 14 patients with acute disseminated encephalomyelitis (ADEM) and 20 controls using a fluorescent bead-based immunoassay. A variety of cytokines, such as IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, G-CSF and MIP-1beta, were significantly elevated in ADEM. In particular, G-CSF showed a marked 38-fold increase compared to the control mean. Significant positive correlations with inflammatory parameters in CSF, such as cell counts and protein levels, were found for IFN-gamma, IL-6 and IL-8. In contrast, IL-17 produced by activated CD4(+) memory T cells was not increased. The results suggested that various cytokines related to activation of macrophages/microglias and Th(1) and Th(2) cells are upregulated in CSF in ADEM.

Chemokines↗
PubMed2006

Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis.

To address the immune mechanism of the long-term beneficial effects of interferon beta (IFN-beta), we measured the intracellular cytokine production patterns of IFN-gamma, IL-4 and IL-13 in peripheral blood CD4+ and CD8+ T cells, which previously displayed alterations during the early course of IFN-beta treatment, in 15 Japanese patients after long-term IFN-beta administration. The patients were treated with IFN-beta-1b 8 x 10(6) units given subcutaneously every other day for a mean period of 34.5 +/- 5.5 months (range: 26-43 months). During the follow-up period, 6 patients experienced 33 relapses, while the other 9 were relapse-free. The results revealed the following cytokine alterations: (1) type 2 cytokine, such as IL-4 and IL-13, were significantly increased in producing cell percentages in both CD4+ (p = 0.0356 and p = 0.0007, respectively) and CD8+ (p = 0.0231 and p = 0.0170, respectively) T cells while IFN-gamma, a representative type 1 cytokine, was significantly decreased in the absolute producing cell numbers (p = 0.0125 in CD4+ T cells and p = 0.0022 in CD8+ T cells) even after approximately 3 years of IFN-beta administration; (2) the intracellular IFN-gamma / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p = 0.0535 and p = 0.0783, respectively), reflecting a strong downmodulation of type 1 cytokine producing cells; and importantly (3) alterations such as the decreased intracellular IFN-gamma / IL-4 ratio in CD4+ T cells and increased percentage of CD8+ IL-13+ T cells compared with the pretreatment levels were only statistically significant in MS patients without relapse during IFN-beta therapy (p = 0.0152 and p = 0.0078, respectively). Therefore, we consider that cytokine deviation toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN-beta, while a higher intracellular IFN-gamma / IL-4 ratio is associated with treatment failure.

Adult↗
PubMed2006

Immunization with heat shock protein 105-pulsed dendritic cells leads to tumor rejection in mice.

Recently, we reported that heat shock protein 105 (HSP105) DNA vaccination induced anti-tumor immunity. In this study, we set up a preclinical study to investigate the usefulness of dendritic cells (DCs) pulsed with mouse HSP105 as a whole protein for cancer immunotherapy in vivo. The recombinant HSP105 did not induce DC maturation, and the mice vaccinated with HSP105-pulsed BM-DCs were markedly prevented from the growth of subcutaneous tumors, accompanied with a massive infiltration of both CD4+ T cells and CD8+ T cells into the tumors. In depletion experiments, we proved that both CD4+ T cells and CD8+ T cells play a crucial role in anti-tumor immunity. Both CD4+ T cells and CD8+ T cells specific to HSP105 were induced by stimulation with HSP105-pulsed DCs. As a result, vaccination of mice with BM-DCs pulsed with HSP105 itself could elicit a stronger tumor rejection in comparison to DNA vaccination.

Adoptive Transfer↗
PubMed2006

Character changes from idiopathic cranial pachymeningoencephalitis.

A 66-year-old man with idiopathic cranial pachymeningoencephalitis was described. He suffered from left orbital pain, and character changes. He became short tempered, and was very attached to trifles. Two years prior to these symptoms, he had developed transient left abducent nerve palsy. Head MRI showed a thickening and enhancement of the dura mater on gadolinium-enhanced T1-weighted images, and high signal intensity lesions at bilateral frontal lobes predominantly in the white matter on T2-weighted images. Biopsies revealed microglial proliferation in the cerebral parenchyma, and mild lymphocytic perivascular infiltration. No evidence of intracranial infection was detected. We therefore treated him with methylprednisolone pulse therapy followed by oral prednisolone. His character became gradually normalized, and bilateral frontal lobe lesions seen on MRI disappeared. This is the first case to describe recurrent pachymeningoencephalitis with character changes, and symptoms were probably due to frontal lobe dysfunction.

Abducens Nerve Diseases↗
PubMed2006

Functional network of the basal ganglia and cerebellar motor loops in vivo: different activation patterns between self-initiated and externally triggered movements.

The basal ganglia and cerebellar loops are known to participate differently in self-initiated (SI) and externally triggered (ET) movements. However, no previous neuroimaging studies have illustrated functional organization of these loops in vivo. Here, we aimed to functionally visualize these loops during motor execution using functional magnetic resonance imaging (fMRI) with structural equation modeling (SEM). Twelve normal subjects (24-29 years old) were scanned while performing five different frequencies of sequential left finger movements using either SI or ET movements. Random effect analysis combined with a parametric approach revealed a significant positive linear dependence of cerebral activation upon movement rate in the right Put, GPi, VL, SMC and SMA during SI tasks. During ET tasks, significant positive linear relationships were found in the right SMC, VPL, left CB and DN, whereas tendency for linear relationships was seen in the right PMv. SEM further showed significant interactions within the right basal ganglia-thalamo-motor loop during SI tasks. In contrast, there were significant interactions within the entire right cerebral hemisphere-left cerebellar loop involving CB, DN, VPL, PMv and SMC during ET tasks. Therefore, our modeling approach enabled identification of different contributions of the motor loops of basal ganglia and cerebellum to SI and ET tasks during motor execution.

Adult↗
PubMed2006

Nationwide survey of juvenile muscular atrophy of distal upper extremity (Hirayama disease) in Japan.

Juvenile muscular atrophy of the distal upper extremity (JMADUE, Hirayama disease) was first reported in 1959 as 'juvenile muscular atrophy of unilateral upper extremity'. Since then, similar patients in their teens or 20s have been described, under a variety of names, not only in Japan, but also in other Asian countries, as well as Europe and North America. Biomechanical abnormalities associated with JMADUE have recently been reported through various imaging examinations, proposing its disease mechanism. Since JMADUE differs from motor neuron disease, or spinal muscular atrophy, this disease entity should be more widely recognized, and early detection and effective treatments should be considered. We report an epidemiological study in Japan. Two nationwide questionnaire-based surveys, conducted in Japan from 1996 to 1998, identified 333 cases. The numbers of patients per year, distribution of ages at onset, mode of onset, time lapse between onset and quiescence, neurological signs and symptoms, imaging findings, and the effects of conservative treatments were analyzed. The peak age was 15 to 17 years, with a marked male preponderance, usually a slow onset and progression, and quiescence six or fewer years after onset. There was a predominantly unilateral hand and forearm involvement with 'cold paresis'. The imaging findings are described.

Adolescent↗
PubMed2006

Intrathecal upregulation of granulocyte colony stimulating factor and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis.

To investigate cytokine/chemokine changes in amyotrophic lateral sclerosis (ALS), we simultaneously measured 16 cytokine/chemokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony stimulating factor [G-CSF], macrophage chemoattractant protein-1 [MCP-1], and macrophage inflammatory protein-1beta) in cerebrospinal fluid (CSF) and sera from 37 patients with sporadic ALS and 33 controls using a multiplexed fluorescent bead-based immunoassay. We also conducted immunohistochemical analyses from 8 autopsied ALS cases and 6 nonneurologic disease controls as well as cell culture analyses of relevant cytokines and their receptors. We found that concentrations of G-CSF and MCP-1 were significantly increased in ALS CSF compared with controls. In spinal cords, G-CSF was expressed in reactive astrocytes in ALS cases but not controls, whereas G-CSF receptor expression was significantly decreased in motor neurons of spinal cords from ALS cases. Biologically, G-CSF had a protective effect on the NSC34 cell line under conditions of both oxidative and nutritional stress. We suggested that G-CSF has potentially neuroprotective effects on motor neurons in ALS and that downregulation of its receptor might contribute to ALS pathogenesis. On the other hand, MCP-1 correlated with disease severity, which may aggravate motor neuron damage.

Aged↗
PubMed2006

[Fibromuscular dysplasia of the basilar artery presenting as cerebral infarction in a young female].

We reported a 20-year-old woman with fibromuscular dysplasia (FMD) of the basilar artery presenting multiple cerebral infarctions. A sudden onset of consciousness disturbance and right hemiparesis was experienced. A neurological examination on day 2 revealed an absence of light and corneal reflexes on the left side, homonymous left upper quadrant anopsia and right hemiparesis with Babinski sign: she was also somnolent. On head MRI, multiple high signal intensity lesions were seen in the right occipital lobe, bilateral thalami and left pons on T2- and diffusion weighted images. Brain angiogram revealed the string of beads sign of the basilar artery, suggesting FMD. Neurological deficits gradually improved in the 2 months that followed, leaving slight hemiparesis and homonymous left upper quadrant anopsia In the following 3 years, no recurrence was seen with aspirin (81 mg/day). FMD in the head and neck usually affects extracranial segments of the carotid and vertebral arteries, while FMD of the basilar artery is extremely rare. To the best of our knowledge, 12 cases with FMD of the basilar artery have been reported; of these, 11 were symptomatic and 5 died. Since FMD of the basilar artery has poor prognosis, attention needs to be paid for FMD in young adults as a differential diagnosis of cerebral infarction in the territory of the basilar artery.

Adult↗
PubMed2006

[Venous infarction associated with carotid-cavernous fistula].

We report an 88-year-old woman who developed a hemorrhagic venous infarction in the left cerebral hemisphere and brainstem, in association with left carotid-cavernous fistula (CCF). Without aura the patient noticed diplopia due to left abducens palsy, and exophthal mos and congestion of the left eye. Brain CT revealed extrusion of the left eye, and dilatation of left superior orbital vein and cerebral cortical veins. She received diagnosis of CCF. Brain CT also revealed a small mass in the left ethmoidal sinus, which was not attached to the CCF. Biopsy of the mass was done under local anesthesia. On the following she had high fever. Her consciousness level deteriorated and she developed right hemiparesis FLAIR images of MRI showed, extensive high signal lesions in the left frontal and temporal cortices, basal ganglia, thalamus, midbrain and pons. These findings were consisted with venous infarction, possibly associated with peri-operative infection and hypovolemia. Intracranial hemorrhage occur in 3% of cases with CCF, but venous infarction was much rarer. The patients with CCF, who show dilatation of cortical veins in CT or MRI, have a higher risk of cerebral hemorrhage or infarction, and should be carefully observed.

Aged, 80 and over↗
PubMed2006

[Hashimoto's encephalopathy with bilateral pallidal lesions presenting memory disturbance and executive dysfunction].

A 76-year-old man began to mistake his family for another person, and fall asleep easily while watching TV. He was treated with donepezil but without any effect. He was referred to our hospital on June. On admission, his consciousness was alert. Cranial nerves and motor functions were normal, but pathological reflexes were positive bilaterally. Serological examinations revealed high titers of antibodies against thyroglobulin and TPO, and antibody against alpha-enolase was positive. Total protein level in CSF was 40 mg/dl and cell counts were normal. On MRI, localized symmetrical lesions were observed in bilateral pallidum to genu of internal capsule. SPECT revealed hypoperfusion areas in bilateral striate bodies and frontal lobes. Neuropsychological examinations indicated impairment of executive function and procedural memory. The diagnosis of Hashimoto's encephalopathy was made and we treated the patient with oral prednisolone 60 mg/day followed by gradual tapering. After the treatment, clinical symptom as well as neuropsychological function improved. Neuropsychological impairment in this case was probably due to the disconnection of the thalamo-frontal projection. This case provides interesting suggestions that Hashimoto's encephalopathy may present with vasculitic infarctions in bilateral MCA perforators, and that this disease should be included in one of the differential diagnoses of cerebral infarctions of unknown etiology.

Aged↗
PubMed2005

Upregulation of vascular growth factors in multiple sclerosis: correlation with MRI findings.

Vascular permeability changes precede the development of demyelinating lesions in multiple sclerosis (MS), and vessel wall thickening and capillary proliferation are frequently seen in autopsied MS lesions. Although vascular growth factors are critical for inducing such vascular changes, their involvement in MS has not been extensively studied. Thus, we examined the involvement of various vascular growth factors in MS according to their clinical phase and subtype. We measured serum levels of vascular endothelial growth factor (VEGF), acidic and basic fibroblast growth factors (FGF) and platelet-derived growth factors (PDGFs)-AA, -AB and -BB in 50 patients with MS (27 opticospinal MS and 23 conventional MS patients) and 33 healthy controls using sandwich enzyme immunoassays. Correlations between growth factor changes and brain and spinal cord MRI findings were then analyzed. Serum VEGF concentrations were significantly higher in MS patients in relapse than in controls (p = 0.0495) and in MS patients in remission (p = 0.0003), irrespective of clinical subtype. Basic FGF was significantly increased in conventional MS patients, but not opticospinal MS patients compared with controls (p = 0.0291), irrespective of clinical phase. VEGF at relapse showed a significant positive correlation with the length of spinal cord lesions on MRI (r = 0.506, p = 0.0319). The results suggest that an increase in serum VEGF concentration might be involved in MS relapse and the formation of longitudinally extensive spinal cord lesions.

Adult↗
PubMed2005

Autoimmunity against neurofilament protein and its possible association with HLA-DRB1*1502 allele in glaucoma.

Glaucoma is understood as a neurodegenerative disease and intraocular pressure has been regarded as the major risk factors for the optic nerve damages. However, recent studies suggested that several risk factors including autoimmunity are also shown to play important roles in glaucoma. To identify the retinal antigen in glaucoma, we used the serological analysis of recombinant cDNA expression libraries (SEREX) approach and quantified IgG antibodies directed against the identified antigens in an ELISA. We identified neurofilament protein and the prevalence of anti-bovine neurofilament light subunit (NF-L) autoantibodies in glaucomatous patients was significantly higher than in healthy controls and patients with other uveitic and optic nerve diseases (P<0.05). In addition, our immunogenetic analysis showed a possible association between HLA-DRB1*1502 allele and the patients positive for anti-NF-L autoantibodies. It suggests that the HLA class II-linked gene may be involved in development of autoimmunity in patients with glaucoma.

Adult↗