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Biomedical subjects

S Izumo

Publications and source records attributed to S Izumo.

At least 199 records · Page 11Linked to original sources

Lymphocyte subsets in muscle biopsies of human T-lymphotropic virus type I carriers with polymyositis.

Recent epidemiologic studies have shown that human T-lymphotropic virus type I (HTLV-I) is associated with polymyositis. To clarify the histological features of HTLV-I positive polymyositis, we studied muscle tissue from two groups of patients with polymyositis, those seropositive for HTLV-I (5 patients) and those seronegative (5 patients). We examined the lymphocyte subsets in muscle biopsies using monoclonal antibodies. In the endomysium, a variable number of T-lymphocytes and macrophages and a smaller proportion of B-lymphocytes were found in both groups. In both HTLV-I positive and negative patients a variable number of T-lymphocytes and macrophages, with a smaller number of B-lymphocytes, were found in the perimysium. As a whole, the T-lymphocytes were predominantly of the helper/inducer phenotype in both groups. We failed to find any specific phenotype distribution among T-cells infiltrating the muscle of HTLV-I carriers with polymyositis.

Adult↗

[Adult-onset neuronal ceroid lipofuscinosis--a case report with biological study].

A 32-year-old male was admitted to our hospital complaining of dementia, gait disturbance and blindness. These symptoms developed at the early two decade and were progressive. On admission, his clinical features included dementia (IQ = 69), spasticity, accentuated deep tendon reflexes, ataxia and hypesthesias in his distal limbs. Brain CT scans showed diffuse cerebral atrophy. On light microscopy, many abnormal lipopigments resembling ceroid and lipofuscin were found in Schwann cells of sural nerve and histiocytes of colon. Ultrastructurally, these materials showed lamellar structure like Zebra bodies. Nine lysosomal enzymes, serum very long-chain fatty acids, serum amino acids and urinary oligosaccharides were all normal. Neuronal ceroid lipofuscinosis (NCL) of adult type was diagnosed on the basis of clinical features, radiological and pathological findings, and biochemical studies. Many previous studies suggested that NCL was a disorder with lysosomal dysfunction. We examined lysosomal protein degradation, using 125I-low density lipoprotein (LDL) in cultured fibroblasts from this patient. The degradation of LDL was normal, compared to control subjects. The activities of cathepsin and lysosomal glycosidases, were also normal. The amount of urinary dolichol has been reported to be elevated in the patients with infantile and late infantile types of NCL. However, no elevation was found in the urine of our patient.

Adult↗

[Significance of anti-HTLV-I antibody in cerebrospinal fluid in diagnosis of HTLV-I associated myelopathy (HAM)].

Anti-HTLV-I antibody was measured in 69 cerebrospinal fluids (CSFs) of cases with typical HTLV-I associated myelopathy (HAM) and other disorders whose symptoms were similar to HAM in order to evaluate the diagnostic significance of anti-HTLV-I antibody in CSF. Both gelatin particle agglutination (PA; Serodia-ATLA) method and recombinant gag-env hybrid protein coated ELISA were employed simultaneously. Antibody titers of both methods showed linear correlation. Cases with typical HAM (24 cases) and HAM with additional neurological manifestations (7 cases) showed high positivity in both methods. Cases with other neurological disorders with possible HAM (11 cases, seropositive) and cases with other neurological disorders without HAM (12 cases, seropositive) showed low positivity with low titer in ELISA, on the other hand, 81% and 67% of those cases were positive in PA method. All cases with seronegative neuroimmunological disorders (15 cases) were negative in CSFs. These findings showed that anti-HTLV-I antibody in CSF is significant in diagnosis of HAM, and both PA and gag-env ELISA are useful to detect anti-HTLV-I antibodies in CSF.

Agglutination Tests↗

Neuropathology of HTLV-I-associated myelopathy--a report of two autopsy cases.

A neuropathological analysis was performed in two autopsy cases of HTLV-I-associated myelopathy. The thoracic spinal cords were most severely affected and the histopathological findings consisted of mononuclear cell infiltration, marked destruction of myelin and axons and astrocytic gliosis. More than half the infiltrated cells were positive for pan-T cell marker; B cells were sparse in the parenchyma and subarachnoid spaces. CD4 and CD8 positive cells were found in the early stages of the lesions. CD8, however, predominated over CD4 in the other stages. It appeared that a chronic inflammatory process had started at the middle to lower thoracic cord and had extended gradually in both directions. The middle thoracic spinal cord is known to have the poorest blood supply, and the horizontal distribution of inflammatory cells at this region correlated with the most distal supply of the anterior spinal artery.

Aged↗

Localization and regulation of c-fos and c-jun protooncogene induction by systolic wall stress in normal and hypertrophied rat hearts.

The effect of changes in left ventricular (LV) systolic force generation on cardiac c-fos and c-jun protooncogene expression was studied by using isolated beating hearts from male Wistar rats. An isovolumic buffer-perfused heart preparation was utilized in which coronary flow and heart rate were held constant and increments in LV balloon volume were used to generate defined levels of LV systolic wall stress. Using Northern and slot-blot analyses, we found that LV tissue from control hearts that generated high levels of LV systolic wall stress expressed 3- to 4.4-fold higher c-fos and c-jun mRNA levels in comparison with tissue from the respective flaccid right ventricles, and in comparison with LV tissue from hearts that generated minimal LV systolic wall stress. To distinguish the role of passive LV diastolic wall stretch from active LV force generation, we found that distension of the LV balloon per se did not have a significant effect on protooncogene induction in hearts perfused with 2,3-butanedione monoxime, which prevents systolic cross-bridge cycling and force generation. In additional hearts studied at a constant LV balloon volume to generate an LV end-diastolic pressure of 10 mm Hg, c-fos mRNA levels were proportional to the magnitude of peak LV systolic wall stress (r = 0.823, P less than 0.05). In these protocols, Fos protein was localized by immunohistochemistry in myocyte nuclei with minimal staining in fibroblasts and vascular smooth muscle. When c-fos and c-jun mRNA expression was compared in hearts with chronic LV hypertrophy due to ascending aortic banding and age-matched control hearts that generated similar incremental levels of LV systolic wall stress, significantly lower levels of c-fos and c-jun mRNA were measured in the hypertrophied hearts. However, there was no difference in protooncogene mRNA expression in response to stimulation by the Ca2+ ionophore A23187. These data suggest that, in this isolated isovolumic beating heart preparation, the active generation of an acute increment in LV systolic force independent of passive diastolic myocardial stretch causes a rapid induction of both c-fos and c-jun, which is down-regulated in the presence of established LV hypertrophy.

Animals↗

Experimental germanium myopathy.

The long-term administration of germanium dioxide (GeO2) to rats produced Ge myopathy characterized by the formation of ragged-red fibers. The earliest pathological changes in experimental Ge myopathy were a decrease in cytochrome c oxidase activity and accumulation of high electron-dense materials in mitochondria. These findings suggest that a mitochondrial dysfunction may be most important in the genesis of experimental Ge myopathy, which could be a useful animal model for the investigation of and therapeutic trials for human mitochondrial myopathies.

Animals↗

Polyneuropathy induced by m-tolyl methyl carbamate intoxication.

A 55-year-old woman who attempted suicide by ingesting 200 ml of m-tolyl methyl carbamate (MTMC) is reported. She was comatose for 3 days and, upon recovery, had notable paraesthesia in her lower limbs and difficulty in walking. Neurological examination revealed sensorimotor polyneuropathy. Sural nerve biopsy revealed marked axonal degeneration with a moderate decrease of myelinated fibres.

Carbamates↗

[Advanced stage of giant axonal neuropathy].

A woman has appeared normal during her neonatal and childhood period except for a short stature. Her parents were healthy and non-consanguineous. At the age of 8, she noticed difficulty in climbing stairs and had tendency to fall. In her 13th year, she developed marked scoliosis and genu valgum. Physical examination at 14 years of age revealed a gentle and shy child of short stature with brown-black kinky hair. Neurological examinations revealed progressive mental retardation, optic nerve atrophy, moderate and coarse nystagmus on lateral and vertical gaze, atrophic tongue with fasciculations, slow and scanning speech, distal muscular weaknesses with diffuse atrophies in the four extremities and sensory deficiencies in all modalities with a glove-stocking type distribution. At the age of 15, she was unable to walk without a wheelchair. During the course she showed slowly progressive muscular weakness, ataxia and decreasing sensation especially in the lower extremities. She died of infection of the respiratory and urinary tracts at the age of 25. Pathologically the abnormalities in the biopsied and autopsied sural nerve were characterized by an advanced stage of nerve fiber degeneration without giant axons. The phrenic nerve obtained at autopsy at 1 to 10 cm from axon terminal revealed the presence of several large focal axonal swelling of 15-20 microns in diameter. On the other hand, sections of the phrenic nerve at 15 cm from axon terminal displayed a mild to moderate reduction in the number of myelinated fibers without giant axons. The difference of pathological findings among these specimens seems to depend on the time as well as the site of the examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Rapid and reversible changes in myosin heavy chain expression in response to increased neuromuscular activity of rat fast-twitch muscle.

Chronic 10 Hz stimulation of rat fast-twitch muscle induced rapid and reversible changes in the tissue levels of fast myosin heavy chain (HC) mRNA isoforms. These changes consisted of a rapid decrease in HCIIb mRNA and a progressive increase in HCIIa mRNA. After 15 days, the HCIIb mRNA normally amounting to approximately 80%, had decreased to less than 5% of the sum of the two HC mRNA isoforms. HCIIb mRNA was again detectable one day after cessation of stimulation and progressively increased at the expense of HCIIa mRNA with ongoing recovery. These results point to a down-regulation of the HCIIb gene by the applied stimulus pattern which, conversely, enhances the expression of the HCIIa gene.

Animals↗

An autopsied case of the Crow-Fukase syndrome: a neuropathological study with emphasis on spinal roots.

An autopsied case of the Crow-Fukase syndrome is reported. Neuropathological findings were as follows: (1) in the sural nerve, there was marked decrease of large and small myelinated fibers. Myelinated fibers showing axonal degeneration and segmental demyelination and remyelination were moderately increased. (2) In the lumbar spinal roots, myelinated fibers showing segmental demyelination and remyelination were frequently observed. The density of myelinated fibers of the ventral root was less at the dural site than the spinal site, while that of the dorsal roots was less at the spinal site than the dural site. (3) In the dorsal root ganglion, there were Nageotte's residual nodules and satelliotosis; (4) in the lumbar and thoracic spinal cord, there was pallor of the dorsal column; and (5) nerve cells showing central chromatolysis were frequently observed in the spinal anterior horn cells. Segmental demyelination and remyelination in the spinal roots and loss of myelinated fibers with axonal degeneration in the sural nerve are main neuropathological features of this syndrome.

Aged↗

Disuse and passive stretch cause rapid alterations in expression of developmental and adult contractile protein genes in skeletal muscle.

Contractile proteins exist as a number of isoforms that show a developmental and tissue-specific pattern of expression. Using gene-specific cDNA probes, the expression of the sarcomeric myosin heavy chain (MHC) multi-gene family and of cardiac (foetal) alpha-actin was analysed in three different rat hindlimb muscles immobilised for 5 days in either the shortened or lengthened positions. For each of the MHC genes normally expressed in adult muscle (slow, IIA and IIB), the effect of disuse alone (immobilisation in the shortened position) upon expression was markedly different to that of passive stretch (immobilisation in the lengthened position) in each of the three muscles. However, the same adult sarcomeric myosin heavy chain gene can be affected in a different, or even opposite, manner by either disuse or passive stretch depending on the muscle in which it is being expressed. The fast IIB MHC gene, for example, exhibits a rapid induction in the slow postural soleus muscle, in response to disuse but no such induction occurs in the faster plantaris and gastrocnemius muscles. Furthermore, the induction of this gene in the soleus was prevented by passive stretch. The MHC gene, normally only expressed in embryonic skeletal muscle, showed a similar response in all three muscles and was reinduced in adult muscle in response to passive stretch but not by disuse alone. In contrast, the isoform of alpha-actin which is normally only present in significant quantities in embryonic skeletal muscle and which is reduced postnatally, is not reinduced by passive stretch but is reduced still further by immobilisation in the shortened position.

Actins↗

Angiotensin II induces c-fos mRNA in aortic smooth muscle. Role of Ca2+ mobilization and protein kinase C activation.

Vasoconstrictors such as angiotensin II (Ang II) play an important role in the pathogenesis of hypertension. These agonists may be responsible for the abnormal vascular smooth muscle cell (VSMC) growth seen in hypertension, either indirectly as a consequence of elevating blood pressure or directly as a result of receptor-mediated effects on VSMC growth. To investigate whether Ang II might directly initiate or modulate some of the "early" genetic programs associated with growth in VSMC, the expression of the proto-oncogene c-fos was studied in cultured rat aortic VSMC. Ang II rapidly induced the accumulation of c-fos mRNA, with maximal levels occurring at approximately 30 min. Induction of c-fos mRNA by Ang II was concentration-dependent, with a maximal response at 100 nM. Ang II induction of c-fos mRNA was blocked by its competitive inhibitor, [sarcosine 1,isoleucine 8]angiotensin II. Induction of c-fos mRNA was not dependent upon Ang II-stimulated intracellular alkalinization or activation of Na+/H+ exchange, but was dependent upon mobilization of intracellular Ca2+ and protein kinase C activation. Epidermal growth factor, a VSMC mitogen, also induced c-fos mRNA in VSMC, but by a mechanism different from that of Ang II. These results demonstrate that the vasoconstrictor hormone Ang II induces in VSMC one of the earliest genes, c-fos, associated with the proliferative response.

Angiotensin II↗