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Biomedical subjects

M Osame

Publications and source records attributed to M Osame.

At least 145 records · Page 8Linked to original sources

Perivascular T cells are infected with HTLV-I in the spinal cord lesions with HTLV-I-associated myelopathy/tropical spastic paraparesis: double staining of immunohistochemistry and polymerase chain reaction in situ hybridization.

HTLV-I-infected cells play an important role in pathogenesis HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Our previous studies of quantitative polymerase chain reaction (PCR) and in situ PCR suggested that T cells infiltrating in the spinal cord lesion were infected with HTLV-I. To elucidate the localization of HTLV-I proviral DNA directly, we performed double staining using immunohistochemistry and PCR in situ hybridization (PCR-ISH). Fresh frozen sections of the spinal cord from four HAM patients taken at autopsy were first immunostained with antibodies to pan T cells (UCHL-1), macrophages (KP-1) and helper/inducer T cells (OPD4). Then PCR-ISH was carried out with specific primers and probe for the HTLV-I pX region. UCHL-1-positive cells were noted around perivascular areas and, to some extent, in the parenchyma. Of the UCHL-1-positive cells, 9.4% (case 1), 9.6% (case 2), 1.1% (case 3) and 6.7% (case 4) became positive in HTLV-I PCR-ISH. UCHL-1-negative cells were HTLV-I PCR-ISH negative and almost all KP-1-positive cells were HTLV-I negative. HTLV-I was localized to OPD4-positive cells in examined lesions of cases 2 and 4. These data are a direct demonstration of HTLV-I proviral DNA localizing to infiltrated T cells in HAM/TSP spinal cord lesions.

Aged↗

Histopathological and ultrastructural features of feline hereditary cerebellar cortical atrophy: a novel animal model of human spinocerebellar degeneration.

Human spinocerebellar degeneration is one of the intractable diseases. We studied the detailed neuropathology of cats with hereditary cerebellar degeneration obtained from the experimental breeding. The findings included almost total loss of Purkinje cells with an increase in Bergmann's glia in the cerebellar hemisphere, preservation of some Purkinje cells in the vermis and moderate neuronal depletion of the olive nucleus. Cerebellar and pontine nuclei were normal. The cerebrum and spinal cord as well as the peripheral nervous system appeared normal. Electron microscopic examination revealed swelling of the distal dendrites of Purkinje cells in the less-affected nodule of the vermis, and clusters of presynaptic boutons without any synaptic contact in the severely affected folia where Purkinje cell bodies and dendrites disappeared. Prolonged existence of presynapses in the molecular and Purkinje cell layers was confirmed by positive immunoreactivity to anti-synaptophysin. Quantitative analysis using electron microscopy demonstrated an apparent increase in the density and mean size of presynapses in the molecular layer of the severely affected folia. These findings indicate that degeneration of Purkinje cells started at the most distal part of the dendrite in this animal model of cerebellar degeneration, and that presynapses, axon terminals of the granular cells and basket cells can exist for a long time even after complete degeneration of the Purkinje cells. Further investigation of this novel animal model may promote a better understanding of pathogenesis of human hereditary cerebellar degeneration.

Animals↗

Retinal manifestations in mitochondrial diseases associated with mitochondrial DNA mutation.

PURPOSE: To scrutinize retinal involvement associated with distinct mitochondrial DNA (mtDNA) defects, we reviewed the records of a consecutive series of patients with various mitochondrial diseases. METHODS: Clinical, laboratory and mtDNA studies were performed in: five patients with Kearns-Sayre syndrome (KSS); six patients with chronic progressive external ophthalmoplegia (CPEO); three patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS); three patients with myoclonic epilepsy and ragged-red fibers (MERRF); 20 patients with Leber's hereditary optic neuropathy (LHON); 30 patients with simple diabetes mellitus. RESULTS: All KSS patients with neurologic and cardiac symptoms associated with a deletion of mtDNA in muscle biopsy specimens showed widespread retinal pigmentary changes characterized by salt- and pepper-like appearance of the fundus. Three of six patients with CPEO, a mild variant of KSS, showed subtle defects at the level of retinal pigment epithelium of the posterior pole, although mtDNA deletion was similar to that in KSS. Of three patients with MELAS syndrome, one patient showed juvenile cataract and mild retinal pigmentary defect in the posterior pole. Of three patients with MERRF syndrome associated with a mtDNA mutation at nucleotide position (np) 8344, one patient showed mild pigment disorder in the posterior pole in addition to optic neuropathy. Two of 20 patients with LHON associated with a mtDNA mutation at np 11778 showed mild pigmentary defect in the macula together with typical optic neuropathy. In addition, two of 30 patients with isolated diabetes mellitus showed a mtDNA mutation at np 3243 (MELAS mutation), but they did not present with any other neurologic or multisystem disorder. CONCLUSION: The retina, in particular the retinal pigment epithelium, is highly vulnerable to be involved by mtDNA defect, and the retinopathy is phenotypically variable and frequently subclinical, depending to some extent on the type or site of mtDNA defect.

Adolescent↗

Human CD4+ T lymphocytes recognize a highly conserved epitope of human T lymphotropic virus type 1 (HTLV-1) env gp21 restricted by HLA DRB1*0101.

HTLV-1 causes two distinct human diseases, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukaemia/lymphoma (ATL). Persistently infected individuals carry a risk of <1% of developing either disease. These basic epidemiological data imply that virus-host interactions, especially immunogenetic factors, influence the outcome of infection. Several studies showed that the HLA class II DR1 DQ5 haplotype is over-represented in HAM/TSP, but rare in ATL. Therefore, we selected four patients with HAM/TSP and one seronegative control who all carried the HLA DR1 DQ5 haplotype. We analysed the CD4+ T lymphocyte response against eight synthetic peptides of HTLV-1 envelope (env) glycoprotein gp21, a crucial target antigen in HAM/TSP. The first of two immunodominant epitopes corresponded to a domain of the HTLV-1 envelope protein which had previously been shown to be essential for HTLV-1 envelope function. The second immunodominant epitope overlapped a highly conserved sequence of the retroviral transmembrane envelope protein. DR1 (DRB1*0101)-restricted T lymphocytes were activated by the conserved peptide sequence in nanomolar concentrations. In contrast, this conserved sequence can also induce non-specific, cAMP-mediated immunosuppressive effects on T cells when added in micromolar concentrations to culture media, as shown by Haraguchi S, Good RA, James-Yarish M, Cianciolo GJ, Day NK, Proc Natl Acad Sci USA 1995; 92:5568-71. Hence, HTLV-1 env gp21 might exert either stimulating immunological or immunosuppressive effects in HTLV-1-infected individuals, depending on the level of its expression and the presence of HLA DRB1*0101.

Amino Acid Sequence↗

Serum amyloid A and P protein levels are lowered by dextran sulfate cellulose low-density lipoprotein apheresis.

The present study describes the short-term effect of dextran sulfate cellulose (DSC) low-density lipoprotein (LDL) apheresis using a plasma separator equipped with a polysulfone (PS) membrane filter (PS/DSC-LDL apheresis) on the serum amyloid A (SAA) and P (SAP) protein levels during treatment in a patient with familial hypercholesterolemia (type IIa, heterozygote). PS/DSC-LDL apheresis markedly lowered both the SAA (reduction percentage, 84.1+/-8.2%) and SAP (91.4+/-5%) levels, which returned to their respective initial levels within 4 days. Experimentally, the levels of both proteins also decreased on passage through the DSC minicolumn without a PS membrane, indicating that the DSC resin had an affinity to both proteins. These results suggest that PS/DSC-LDL apheresis may be advantageous for amyloid protein accumulating disorders, including amyloidosis and atherosclerosis.

Adult↗

Mushroom worker's lung resulting from indoor cultivation of Pleurotus osteatus.

Indoor cultivation of oyster mushroom Pleurotus osteatus lead to an outbreak of extrinsic allergic alveolitis in two workers. High titer of indirect fluorescent antibody and positive precipitins against basidiospores of P. osteatus were demonstrated in sera of the patients. Mushroom workers should protect themselves from the basidiospores, being aware of their pathogenicity.

Adult↗

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in HTLV-I-associated myelopathy.

Matrix metalloproteinases (MMPs) have been reported to be involved in inflammatory disorders of the central nervous system (CNS). However, little is known about the role of MMPs in the pathogenesis of HTLV-I-associated myelopathy (HAM)/Tropical spastic paraparesis (TSP). To address this issue, we examined the tissue expression and localization of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) in the spinal cord lesions of HAM/TSP using immunohistochemistry. In addition, the blood and cerebrospinal fluid (CSF) levels of MMPs and TIMPs of the patients with HAM/TSP were determined using sandwich enzyme immunoassays (SIA) and gelatin zymography. Immunohistochemical studies revealed that collagen IV and decorin immunoreactivity on the basement membrane of CNS parenchymal vessels was partially disrupted where inflammatory mononuclear cells infiltrated in active-chronic lesions of HAM/TSP. In these lesions, MMP-2 (gelatinase A) was immunostained mainly on the surface of foamy macrophages and lymphocytes, whereas MMP-9 (gelatinase B) expression was positive in the intravascular and perivascular mononuclear cells but not on foamy macrophages. In contrast, inactive chronic lesions of the spinal cords of the HAM/TSP contained fewer MMP-2-positive or MMP-9-positive mononuclear cells than active-chronic lesions. Many parenchymal vessels had thickened vascular walls which showed increased immunoreactivity to decorin. SIA revealed that production levels of MMP-2 and MMP-9 in both blood and CSF were higher in the patients with HAM/TSP than those in non-inflammatory other neurological disease controls (ONDs). Using zymography, proMMP-9 was detected more frequently in the CSF of patients with HAM/TSP than those in ONDs. Taken together, our data indicate that MMP-2 and MMP-9 may play an important role in the blood-brain barrier breakdown and tissue remodeling in the CNS of HAM/TSP.

Aged↗

HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia.

The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

Adult↗

An autopsy case of peripheral neuroepithelioma in posterior mediastinum with p53 point mutation.

An 18-year old male was admitted to our hospital complaining of back pain. His chest computed tomography showed a tumor in the posterior mediastinum. Open biopsy was performed, and a diagnosis of peripheral neuroepithelioma was made. No genetic abnormalities were detected in the DNA obtained from the biopsy specimen. He received chemotherapy and radiation several times. These treatment regimens were effective, but he relapsed 14 months later and died of respiratory failure due to tumor growth. Autopsy examination revealed a large tumor which occupied almost the entire right thoracic cavity, but there was no evidence of metastasis to other organs. Chromosomal translocation t(14;17) (q24;p12.2) and point mutation of exon 5 of the p53 gene were detected.

Adolescent↗

Two cases of idiopathic CD4+ T-lymphocytopenia in elderly patients.

We present 2 cases of idiopathic CD4+ T-lymphocytopenia (ICL) in elderly patients. Case 1, a 73-year-old man, with pneumonia had received several antibiotics with unsuccessful results at another hospital. On admission, his CD4+ T-lymphocyte count was 109/microl and Pneumocystis carinii was detected by bronchoalveolar lavage fluid staining. No evidence of human immunodeficiency virus (HIV) infection was found. Despite therapy, the patient died of respiratory failure. Case 2, a 72-year-old man, contracted severe pneumonia, and Hemophillus influenzae was believed to be the pathogen. On admission, his CD4+ T-lymphocyte count was 238/microl. No evidence of HIV infection was found. He received antibiotics and improved successfully. We suggest that ICL may currently be incubating in a number of elderly pneumonia patients.

Aged↗

Pulmonary manifestations in cerebrotendinous xanthomatosis.

We investigated five cases with cerebrotendinous xanthomatosis (CTX) with particular reference to biochemical and pathological pulmonary disorders. To date, few reports discuss the pathophysiology of pulmonary disorders of CTX patients. This study is the first investigation of such pulmonary disorders. All 5 patients had no pulmonary symptoms and no disturbances on radiological studies and pulmonary function tests. However, in bronchoalveolar lavage (BAL) fluids, many cells with cruciform reflexes, which is characteristic of intracellular sterol accumulation, were found under phase contrast microscopy. Biochemically, cholestanol was found to be increased in the BAL fluid as well as in serum. Pathological findings of transbronchial lung biopsy (TBLB) samples disclosed foamy macrophages and small granulomas in alveolar septa. In conclusion, the lung was apparently involved in CTX, and the lesions were characterized with the accumulation of foamy and giant cells with a high concentration of cholestanol, which likely results in the formation of foreign body granulomas.

Adult↗

Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP.

In order to examine the effect of HTLV-I proviral load on the pathogenesis of HAM/TSP, we measured the HTLV-I proviral load in peripheral blood mononuclear cells (PBMC) from a large number of HAM/TSP patients and asymptomatic HTLV-I carriers. To measure the proviral load, we used an accurate and reproducible quantitative PCR method using a dual-labeled fluorogenic probe (ABI PRISM 7700 Sequence Detection System). The mean +/- standard error of mean (s.e.m.) HTLV-I proviral copy number per 1 x 10(4) PBMC was 798 +/- 51 (median 544) in 202 HAM/TSP patients; 120 +/- 17 (median 34) in 200 non HAM-related (general) asymptomatic HTLV-I carriers (RC); and 496 +/- 82 (median 321) in 43 asymptomatic HTLV-I carriers genetically related to HAM/TSP patients (FA). The prevalence of HAM/TSP rises exponentially with log (proviral load) once the proviral load exceeds 1% PBMC. The HTLV-I proviral load of female patients with HAM/TSP was significantly higher than that of male patients, however there was no significant difference in proviral load between sexes in RC. There was a significant correlation between the proviral load and the concentration of neopterin in CSF of HAM/TSP patients. These results indicate that the HTLV-I proviral load in PBMC may be related to the inflammatory process in the spinal cord lesion. The increased proviral load in FA suggests the existence of genetic factors contributing to the replication of HTLV-I in vivo.

Adult↗

[Recent advance in neuroimmunology].

Many important reports have been published during these several years in Japan in the field of neuroimmunology. Serum vascular endothelial factor (VEGF) levels in Crow-Fukase (POEMS) syndrome were about 15 to 30 times than those in the control subjects and other neurological disorders. The overproduction of VEGF may be relevant to the pathogenesis of most of the manifestations including neuropathy. We speculate that VEGF may affect the blood nerve barrier by increasing microvascular hyperpermeability and thereby increasing endoneural pressure subsequent to edema. In Isaacs' syndrome, voltage-gated potassium channel (VGKC) were suppressed by anti-VGKC antibodies. The patch clamp study indicate that the pathophysiology of the suppression of VGKC seems to be due to the increased degradation of VGKC. By the recent nationwide survey, the total number of HTLV-I-associated myelopathy (HAM) patients in Japan is now estimated as 1,432. A most likely pathological mechanism of HAM is that cytotoxic T lymphocytes attack the HTLV-I infected lymphocytes infiltrating the central nervous system, resulting a surrounding nervous tissue damage by bystander mechanism.

Autoantibodies↗

[The effect of cigarettes on somatosensory potentials].

INTRODUCTION AND OBJECTIVE: The physiological and pathological effects of cigarettes on the nervous system have been widely studied, but none of the investigations carried out has enabled us to determine the degree to which nicotine may affect the central pathways of somatosensorial evoked potentials in humans. MATERIAL AND METHODS: Following parameters established internationally for investigation of the effects of nicotine on the nervous system, we find that the N18 wave obtained by stimulation of the median nerve before smoking completely disappears after smoking for 3 minutes and reappears 10 minutes after smoking has stopped. CONCLUSIONS: Therefore, we conclude that the action of nicotine on these evoked potentials is mainly subcortical, and for this reason it is essential to investigate the toxicological history before carrying out any clinical or neurophysiological study, since this might affect the results obtained.

Adult↗

[Acute isolated levator palpebral myositis].

A 17-year old man developed acute onset blepharoptosis of the right upper eyelid with swelling. On examination, the patient exhibited right blepharoptosis without limitation of eye movement. MRI revealed swelling of right levator palpebral muscle. Oral steroid administration led to complete resolution of the blepharoptosis within 3 weeks. Isolated levator palpebral myositis is a rare disease, but, it is important for differential diagnosis on patients with blepharoptosis.

Adolescent↗

[A case of pulmonary infiltration with eosinophilia caused by Ascaris suum].

A 46-year old man was admitted to our hospital with dry cough and diarrhea. His chest CT showed diffuse subpleural small nodular shadows. Eosinophilia and an increase of serum IgE were detected. Eosinophils were also increased in BALF. An antibody against Ascaris suum was positive in serum while other causes of eosinophilia (e. g., drugs, fungus, collagen disease) were absent. Ivermectin was administered and the diarrhea improved within 3 days. The abnormal chest shadows and dry cough disappeared 3 months later. Pulmonary infiltration with eosinophilia (PIE) syndrome caused by Ascaris suum was diagnosed because of the clinical course and serum examination results. Recently, zoonoses are increasing with the boom of oversea travel and "natural" foods. We report a case of PIE syndrome caused by Ascaris suum and describe the clinical features and the social significance including the origin of this disease.

Animals↗

[A case of pleuritis caused by strongyloides in a carrier of T-cell lymphoma virus type I (HTLV-I)].

A 73-year-old woman was admitted to our hospital complaining of dyspnea, fever and general edema. Chest roentgenogram showed bilateral pleural effusion and cardiomegaly. Cardiovascular examination demonstrated atrial tachycardia and left ventricle dysfunction, suggesting congestive heart failure. She was sero-positive for human T-cell lymphoma virus I (HTLV-I). The dyspnea and general edema improved after therapy for heart failure. Because the pleural effusion persisted after therapy, thoracentesis was performed. The pleural effusion was an exudate, and Strongyloides sterocoralis was detected by microscopy. Two courses of thiabendazole (1,500 mg/day, 3 days) were given orally. After this therapy, the pleural effusion improved markedly. This case suggests that Strongyloides stercoralis may be a causative agent of pleuritis in HTLV-I endemic areas.

Aged↗

[Pulmonary sclerosing hemangioma with specific CT findings].

A 44-year-old woman was admitted to our hospital for evaluation of an abnormal lung shadow. Chest computed tomography (CT) revealed a tumor surrounded by air-space and an infiltrative shadow in the right S2. Right upper lobectomy was performed and pulmonary sclerosing hemangioma was diagnosed. Usually, pulmonary sclerosing hemangioma shows a solitary round nodule on a chest CT scan. We report a case of pulmonary sclerosing hemangioma with an unusual shadow on a chest CT scan, and review the literature.

Adult↗