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Biomedical subjects

M Osame

Publications and source records attributed to M Osame.

At least 253 records · Page 14Linked to original sources
PubMed1995

Immunological abnormality in patients with lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare hereditary disorder manifesting hyperammonemia induced by low levels of basic amino acids, these low levels being due to the impaired transport of these acids in the intestinal mucosa and the renal tubules. Low serum arginine levels and probably the consequently low in vivo levels of nitric oxide (NO), which against acts as a physiological and immunological mediator/modulator, are thought to influence the immunological status in patients with LPI. Accordingly, this study was conducted to. We found that patients with LPI had leukocytopenia, high serum IgG levels, a high ratio of CD44B4-positive lymphocytes (helper inducer) to CD42H4-positive lymphocytes (suppressor inducer), low levels of leukocyte phagocytic, cytotoxic, and natural killer cell activity, and increased spontaneous proliferation of lymphocytes. These results were probably the consequence of persistent low NO levels in vivo.

Adult↗
PubMed1995

Type II muscle fibers are stained by anti-Fas antibody.

To examine whether apoptosis related proteins are present in skeletal muscles we studied biopsied muscles immunohistochemically and by Western blot analysis. Biopsied muscles from patients with several disorders were studied with anti-Fas antibody and anti-BCL2 antibody. Type II muscle fibers identified by ATPase staining were positively stained by anti-Fas antibody in both normal control and diseased muscles. Anti-BCL2 antibody did not stain any muscle fibers. Western blot analysis using anti-Fas antibody showed a single band at 45 kDa in both skeletal muscle and lymphocytes. Anti-Fas antibody has been reported to induce apoptosis in the cells. The presence of anti-Fas antibody reactive materials in type II muscle fibers might be related to type II fiber atrophy in muscular disorders.

Antibodies, Monoclonal↗
PubMed1995

Anti-viral and immunomodulatory effects of interferon-alpha on cultured lymphocytes from patients with human T lymphotropic virus type I-associated myelopathy (HAM/TSP).

In contrast to therapeutic benefits of interferon-alpha (IFN-alpha) in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the mechanisms underlying its clinical efficacy. To investigate the anti-viral and/or immunomodulatory properties of IFN-alpha in HTLV-I infection, the effects of IFN-alpha on HTLV-I-induced in vitro phenomena were evaluated. In vitro activation of HTLV-I in fractionated CD4+ T lymphocyte-rich cells (CD4+ cells) could be demonstrated by increased thymidine incorporation into the cells, detection of proviral HTLV-I and viral RNA, and by assays of reverse transcriptase activities in culture supernatants. T cell immune responses were evaluated by thymidine incorporation into CD8+ T lymphocyte-rich cells (CD8+ cells) responding to cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens. It could be shown that IFN-alpha suppressed both the in vitro activation of HTLV-I and the CD8+ cell response. Moreover, 1 day supplementation of IFN-alpha as a pretreatment was sufficient for the induction of these properties. These findings, together with the clinical efficacy of IFN-alpha administration in patients with HAM/TSP, support the view that viral activation and T cell responses are critical components in the pathogenic processes involved in HAM/TSP.

Antiviral Agents↗
PubMed1995

Abnormal expression of heparin sulfate proteoglycan on basal lamina of muscle fibers in two Japanese patients with adhalin deficiency.

We recently reported the selective reduction of the B1 subunit of laminin in two Japanese patients with adhalin deficiency. We here investigated immunohistochemically the expression of other components of the extracellular matrix (ECM), including collagen type IV, heparan sulfate proteoglycan can (HSPG), chondroitin-4-sulfate proteoglycan, decorin, and fibronectin in adhalin deficiency, compared with other types of muscular dystrophy. We found a reduction of HSPG on the basal lamina surrounding each muscle fiber in adhalin deficiency compared with HSPG in other diseases. This finding may be characteristic evidence of the disturbance of the sarcolemma-ECM interaction and the sarcolemmal instability in adhalin deficiency. Recently, a direct role of HSPG in fibroblast growth factor (FGF) signal transduction was demonstrated. Further investigation is required to determine if the dysfunction of FGF is relevant to the pathogenesis of adhalin deficiency.

Adolescent↗
PubMed1995

Sequence analysis of human T cell lymphotropic virus type I (HTLV-I) Env genes amplified from central nervous system tissues of patients with HTLV-I-associated myelopathy or leukemia.

Human T cell lymphotropic virus type I (HTLV-I) is a retrovirus that has been linked to HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), a chronic or inflammatory neurological disease with some resemblance to multiple sclerosis. We used the polymerase chain reaction to amplify viral env genes in foci of inflammation and demyelination in the nervous system to adduce additional evidence of the association of HTLV-I with the neuropathological changes in HAM/TSP, and document in this report such an association. We also sought evidence of a distinct viral species in the lesions by amplifying, cloning and sequencing the env genes from tissues sections in which there were pathological changes. We did not find changes in the env gene that correlated with HTLV-I-associated neurological disease vs adult T cell leukemia or with the nervous system vs peripheral blood and lymphoid organs. We did, however, find evidence of extensive mutation and possibly deletions in the env gene in HTLV-I-associated neurological disease. We interpret these findings of increased genetic diversity as a reflection of higher rates of viral replication in HTLV-I-associated myelopathy that support a model of pathogenesis in which increased viral replication activates immune cells that subsequently enter the nervous system and cause injury by immunopathological mechanisms.

Adult↗
PubMed1995

Midkine (MK) expression in extraembryonic tissues, amniotic fluid, and cerebrospinal fluid during mouse embryogenesis.

Midkine (MK) and pleiotrophin (PTN) constitute a new family of heparin-binding growth factors. Extraembryonic membranes and the placenta of the mouse expressed MK mRNA at 11.5 days gestation. While the MK mRNA level in extraembryonic membranes decreased during embryogenesis, that in the placenta remained unchanged. Immunohistochemical studies showed that Mk was located in the yolk sac and in the amnion at 11.5 days gestation. PTN mRNA expression was weak in extraembryonic membranes and was scarcely detectable in the placenta. Western blot analysis revealed the presence of MK in amniotic fluid and cerebrospinal fluid, in amounts of more than 1 microgram/ml, raising the possibility that MK delivered by these fluids participates in the regulation of organogenesis. Transport of MK from the site of its synthesis appears to also occur in the adult kidney, since MK mRNA and the MK protein are localized in different regions of the kidney.

Amino Acid Sequence↗
PubMed1995

Familial mitochondrial encephalomyopathy with deaf-mutism, ophthalmoplegia and leukodystrophy.

We report two sisters (32 and 36 years old) with familial deaf-mutism, progressive external ophthalmoplegia, leukodystrophy and mitochondrial myopathy. T2-weighted brain MRI demonstrated diffuse symmetrical high intensity areas in the white matter. Their muscle biopsies showed ragged-red fibers and cytochrome c oxidase (CCO)-negative fibers. CCO activity in biopsied muscle decreased to about 20% of normal control. They had no deletions of the mitochondrial DNA and no point mutations in mitochondrial tRNA. Their brother was diagnosed as having Kugelberg-Welander disease, grand mal seizures and urinary dysfunction. Their parents and grandparents had consanguinity. Three relatives were found to have deaf-mutism without accompanying ophthalmoplegia. This rare combination of mitochondrial encephalomyopathy and familial deaf-mutism might be caused by a nuclear DNA mutation in these sisters.

Adult↗
PubMed1995

Human T-cell lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis with acute type of adult T-cell leukemia.

We report a 47-year-old Japanese woman with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) combined with acute type adult T-cell leukemia (ATL). The susceptibility for HAM/TSP and acute type of ATL is hitherto explained by human leukocyte antigen (HLA) haplotype-linked immune responsiveness to HTLV-I. This patient's HLA (A24Cw1B54DR4DQ4/A24Cw3B51DR8DQ1) included a HAM-associated HLA haplotype. This suggests that HAM patients with HAM-associated HLA haplotype can also develop the acute type of ATL.

Adult↗
PubMed1995

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP): recent perspectives.

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a well-defined clinicopathological entity, and approximately 1,900 patients with HAM/TSP have been reported in the world. Improved polymerase chain reaction (PCR)-based in situ techniques have allowed a better appreciation of the cellular localization of the virus activation in infected patients, and there is accumulating evidence that HAM/TSP is characterized by a distributional bias of viral activation between the blood flow and central nervous system (CNS). This review summarizes the current status of our understanding of HAM/TSP, and emphasizes the possible pathogenic involvement of cellular interactions between infected cells and responding immunocompetent cells in the CNS of patients with HAM/TSP. In addition, the notable systemic manifestations with or without myelopathy in HTLV-I-infected individuals are described.

Humans↗
PubMed1995

A hemophiliac with human immunodeficiency virus (HIV)-1-associated dementia complex.

We report a 29-year-old male hemophiliac with human immunodeficiency virus (HIV)-1-associated dementia complex, who died 2.5 months after the onset of dementia. The patient's cognitive abnormalities including forgetfulness, loss of concentration and slowing of thought appeared about 7 years after HIV infection. His neurological symptoms were characterized as progressive dementia, episodic consciousness loss, transverse myelopathy and peripheral neuropathy. He had generalized slow waves in electroencephalogram (EEG), progressive cerebral atrophy and a diffuse high intensity lesion in the white matter as shown by T2-weighted brain magnetic resonance imaging (MRI). We emphasize the significance of neurological complications, especially acute progressive dementia, in Japanese patients with acquired immunodeficiency syndrome (AIDS).

AIDS Dementia Complex↗
PubMed1995

HTLV-I-associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings.

We studied the clinical features and laboratory findings in 213 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis as diagnosed in Kagoshima University Hospital. Some aspects of clinical features in HTLV-I-associated myelopathy/tropical spastic paraparesis were characterized by mode of HTLV-I transmission and age of onset. The patients with onset after 15 years old and no history of blood transfusion before the onset of the disease (151 patients, group I) showed a shorter interval between the time of disease onset and that of inability to walk. The patients with onset before 15 years old and without history of blood transfusion (21 patients, group II) had short stature and slow progression of the disease. The interval time and the progression of the disease in patients with history of blood transfusion before onset of disease (41 patients, group III) were in between those of the above two groups. Patients whose ages of onset were older than 61 years old showed a faster progression than those with younger onset regardless of the mode of HTLV-I transmission. HTLV-I-associated myelopathy/tropical spastic paraparesis patients often also showed other organ disorders such as leukoencephalopathy (69%), abnormal findings on chest X-ray (50%), Sjögren syndrome (25%) and arthropathy (17%). The patients with low anti-HTLV-I antibody titers in the cerebrospinal fluid (2X-8X by PA method) had an older age of onset on average, milder clinical symptoms and lesser increase of neopterin in the cerebrospinal fluid than those in the high titer subgroup whose titers were higher than 1024X in cerebrospinal fluid regardless of the mode of HTLV-I transmission. We speculate that the clinical course of HTLV-I-associated myelopathy/tropical spastic paraparesis mainly shows a slow progression which consists of an initial progressive phase (probably an inflammatory phase) and a latter chronic phase, although some patients showed acute/subacute onset and rapid progression.

Acute Disease↗
PubMed1995

Frequent mutation in pX region of HTLV-1 is observed in HAM/TSP patients, but is not specifically associated with the central nervous system lesions.

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia (ATL) and of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Recently it has been reported that defective HTLV-1 provirus was detected frequently in the central nervous system (CNS) lesions of HAM/TSP patients. Here we investigated sequence variations of the pX region of HTLV-1 in the CNS and peripheral blood lymphocytes (PBL) of the same patient. The results analyzing 9-13 clones isolated from each specimen indicated that the pX region is highly variable within a patient with HAM/TSP, and the mutations were found at almost random positions within the sequences analyzed. The frequency and pattern of those mutations did not appear to differ significantly between the CNS and PBL of the same patient, although they differed among patients. Similarly, frequent mutations were observed in an asymptomatic carrier of HTLV-1, although the variability was moderate, suggesting that the high variability of the pX sequence is not a specific event in HAM/TSP. However, one asymptomatic carrier showed much less frequent variations very similarly to an ATL patient; both of them harbored clonally expanded infected cells. Thus the apparent low variability was explained by clonal selection of a single species of the provirus by the clonal proliferation of infected cells. These results clearly indicate that mutations including defectives are not specifically associated with the CNS lesions in HAM/TSP patients, but suggest that the random mutations simply reflect the rate of viral replication in individuals and the variants were not inherited frequently.

Adult↗
PubMed1995

[The clinical usefulness of botulinum toxin type A for spasmodic torticollis and facial spasm].

We studied the clinical effectiveness of botulinum toxin type A for spasmodic torticollis and that for facial spasm by multicenter, non-blinded study. The freeze-dried crystalline botulinum toxin type A (AGN 191622; Allergan Inc., Irvine, CA) was injected into the hyperactive muscles and the clinical course was followed for 22 weeks. Repeated injections were done, if necessary, with an interval of 4 weeks. The toxin was highly effective in both disorders. In spasmodic torticollis, clinical severity improved in 38 (63.3%) and the global improvement was seen in 39 (65.0%) out of 60 patients. Subjective improvement was seen in 56 (93.3%). In facial spasm, 52 (92.9%) out of 56 patients improved after the treatment. Unfavorable reactions, mainly consisting of neck muscle weakness and dysphagia in torticollis and facial weakness in facial spasm, were mostly due to the excessive action of the toxin. They were usually mild and transient. No patients discontinued the trial because of side effects. Botulinum toxin injection is a very useful and safe method for the symptomatic treatment of spasmodic torticollis and facial spasm.

Adolescent↗
PubMed1995

[Treatment of spastic paraparesis with botulinum toxin with reference to beneficial effects, disease severity and long-term treatment].

We administered local botulinum toxin injections on the leg adductors of 12 patients with spastic paraparesis (9 patients with HAM, 2 patients with spinal spastic paraparesis, 1 patient with an identified degenerative disease). Two of them were wheelchair-bound and the other patients could walk with or without help. The patients were assessed by the time to walk 10 m and the spasticity score which was derived from the degree of muscle tone and spasm frequency of leg adductors. After the initial injection, 7 of the 12 patients improved spasticity scores and 8 of the 10 patients could walk 10 m within a shorter time. The time to walk 10 m was markedly shortened in moderate cases. However, one patient complained of leg weakness and the time to walk 10 m was prolonged. Five of the 12 patients received injections 3 to 7 times, and were followed up for a mean of 16.2 months. In 4 of the 5 patients, repeated injections could maintain the improvement of spasticity score and time to walk 10 m. However, injection was discontinued in one patient because of leg weakness. The other side effects were pain and swelling at the injected site and dysarthria. However, these side effects were slight and transient and did not require treatment. No other systemic side effects were observed. In conclusion, the beneficial effects of botulinum injections to spastic paraparesis were (1) improvement of objective symptoms in mild cases, (2) improvement of ADL in moderate cases, and (3) improvement of objective symptoms and ease of nursing care in severe cases. Furthermore, we confirmed the long-term efficacy and safety of botulinum toxin.

Adult↗
PubMed1995

[Adhesion to fibronectin regulates expression of adhesion molecules on eosinophils].

To elucidate the mechanism for the accumulation of eosinophils through adherence in allergic inflammation, we investigate whether adhesion of eosinophils to extracellular matrix (ECM) regulates the expression of adhesion molecules on eosinophils. Highly purified eosinophils obtained from asthmatic patients were cultured on BSA or fibronectin (FN) coated plates for 4 or 48 hours. After then, removed cells were examined about the expression of each adhesion molecule. Cultured on FN resulted in the increment of the expressive CR 3 (CD11b) (BSA vs FN; MFI ratio 10.50 vs 12.09 p < 0.05), and decrement of the expressive VLA-4 (CD49d) on the eosinophils (3.93 vs 2.91 (4 h) p < 0.05, 2.86 vs 2.09 (48 h) p < 0.05). Thus, we could conclude that eosinophils adhesion to ECM via adhesion molecules might play an important role in the pathogenesis of allergic inflammation through the involvement in the regulation of the expression of adhesion molecules on eosinophils.

Cell Adhesion↗
PubMed1995

[Paroxysmal dystonic choreoathetosis with chronic hemolytic anemia and morphologically abnormal erythrocytes].

A 38-year-old man was admitted to our hospital because of paroxysmal involuntary movement. He had a normal birth and normal development. No other members of his family had similar symptoms. He had attacks of choreoathetoic involuntary movement without loss of consciousness since about 11 years of age. Paroxysmal choreic movement occurred once or twice a month and lasted for 30 minutes to 4 hours. The attacks were intractable with phenytoin, phenobarbital, valproic acid, etc. He had slight disturbance of visual acuity due to toxoplasmosis and low intelligence (IQ 59, WAIS-R test). There were no other abnormal findings on general and neurological examinations. He was diagnosed as paroxysmal dystonic choreoathetosis (PDC) because of the typical attacks of paroxysmal choreic movement. He had macrocytic anemia with elliptocytes (13%) and stomatocytes (12%) but no acanthocytosis. There were increased reticulocytosis and low level of haptoglobin. Bone marrow aspiration showed increased erythroblasts. However, other hemolytic findings including bilirubin levels, Coombs test, osmolality tolerance test were normal. Biochemical analyses of erythrocyte membrane proteins and lipids, glycolytic enzymes activities and intermetabolites contents showed no abnormality. EEG revealed slow waves without abnormal paroxysmal discharges, and CT revealed no abnormal calcification. T2 weighted MRI showed bilateral multiple high intensity spots in the subcortical area, but no atrophy of the caudate nucleus. The pathogenesis of PDC is still unknown. In the present case, we suspect that a biochemical defect which had not been disclosed might result in abnormal erythrocyte membrane and PDC.

Adult↗
PubMed1995

Clinical neurophysiological comparative study on HTLV-1 associated myelopathy/tropical spastic paraparesis.

In order to determine the neurophysiological characteristics of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) throughout the world, we analyzed and compared the most common clinical neurophysiological studies (CNPS) performed in this entity from those places with a high prevalence and interesting regional differences were noted. African patients showed a noteworthy involvement of the peripheral nervous system (PNS). Chilean patients displayed a more circumscribed abnormality around the spinal cord. The migrants from the West Indies to England showed important visual, and somatosensory evoked potential (SSEP) alterations in the upper limbs (UL). Japanese patients also presented some involvement of the PNS, but their illness duration was less protracted than that observed in other countries. The differences found in visual pathways and PNS involvement among these groups were statistically significant (p < 0.05). Thus, this study shows not only a widespread subclinical involvement in both central and PNS in HAM/TSP, but also strongly supports the idea that the lesion distribution and progression of this disease are different among countries. Such differences could likely be due to the action of the so-called environmental co-factors present in each of these areas which should be promptly investigated.

Human T-lymphotropic virus 1↗