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Biomedical subjects

M Osame

Publications and source records attributed to M Osame.

At least 19 recordsLinked to original sources
PubMed1992

Frequent clonal proliferation of human T-cell leukemia virus type 1 (HTLV-1)-infected T cells in HTLV-1-associated myelopathy (HAM-TSP).

Human T-cell leukemia virus type 1 (HTLV-1) integrates its proviruses into random sites in host chromosomal DNA. Random integration of the proviruses was observed in asymptomatic HTLV-1 carriers and patients with HTLV-1-associated myelopathy (HAM/TSP). However, clonal integration has been reported in patients with adult T-cell leukemia (ATL), including that in the smoldering, chronic, and acute states, indicating clonal expansion of infected cells. In this study, we found that about 20% of HAM/TSP patients and their seropositive family members harbored subpopulation(s) of clonally proliferated cells infected with HTLV-1, although they still maintained randomly infected cells as a major population. These clones were stable during examination periods of 4 months to 3 years. However, these carriers or HAM/TSP patients did not show any significant indication of ATL. This extremely high frequency of clonal expansion of HTLV-1-infected cells indicates that some clones of HTLV-1-infected cells have a tendency to proliferate more efficiently than the other population without malignant transformation.

Cell Division↗
PubMed1992

A novel primer extension method to detect the number of CAG repeats in the androgen receptor gene in families with X-linked spinal and bulbar muscular atrophy.

X-linked spinal and bulbar muscular atrophy (SBMA), an adult-onset form of motor neuron disease, was recently reported to be caused by amplification of the CAG repeats in the androgen receptor gene. We report here a simple and rapid strategy to detect the precise number of the CAGs. After the DNA fragment containing the CAG repeats is amplified by the polymerase chain reaction, a primer extension is carried out; the extension of the end-labelled reverse primer adjacent to 3' end of CAG repeats stops at the first T after CAG repeats with the incorporation of dideoxy ATP in the reaction mixture. The resultant primer products are analysed by denaturing polyacrylamide gel electrophoresis and autoradiography. This method could be quite useful to detect not only CAG repeats in SBMA but also other polymorphic dinucleotide and trinucleotide repeats.

Adult↗
PubMed1992

Failure to detect HTLV-I by in situ hybridization in the biopsied muscles of viral carriers with polymyositis.

Direct infection of muscle fibers by human T-lymphotropic virus type I (HTLV-I) has recently been reported in a patient with polymyositis infected with both HTLV-I and human immunodeficiency virus (HIV). Coinfections of these viruses are frequently found in the United States. In Kagoshima, Japan, patients with polymyositis have a significantly increased incidence of seropositivity to HTLV-I alone, when compared with the general population of Kagoshima. In this study, we examined muscle tissue from 6 HTLV-I-positive patients with polymyositis from Kagoshima. To detect HTLV-I products, sensitive immunohistochemistry and in situ hybridization analysis were performed. These were compared with muscle fibers from a well-characterized transgenic mouse model which expressed HTLV-I tax. No specific signals were detected in the biopsied muscles of patients with polymyositis infected with HTLV-I alone. HIV co-infection may, therefore, augment HTLV-I expression through either immunosuppression or direct viral interactions.

Adult↗
PubMed1992

Cerebrotendinous xanthomatosis: cranial CT and MRI studies in eight patients.

We report the findings on cranial computed tomography (CT) and magnetic resonance imaging (MRI) and their correlation with the clinical manifestations, disease severity and biochemical abnormalities in eight patients with cerebrotendinous xanthomatosis. CT revealed cerebral atrophy in seven cases, cerebellar atrophy in four and focal low density lesions in the cerebral white matter in two. T2-weighted MRI showed high signal lesions in the cerebral white matter, focal in four cases and diffuse in one, and in the globus pallidus in three patients, two of whom also had lesions in the cerebellar white matter. While severely affected patients showed variable CT and MRI abnormalities, our cases did not show the dramatic findings expected from the neurological manifestations. Diffuse lesions in the cerebral and cerebellar white matter have been emphasized in previous reports, but in our study the focal lesions in the cerebral white matter were also present; the globus pallidus was frequently involved.

Achilles Tendon↗
PubMed1992

Pathological changes in skeletal muscle in HTLV-I-associated myelopathy.

The main lesion site of HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the pyramidal tract. In some HAM patients, clinical symptoms and findings indicate neuromuscular involvement, such as muscular atrophy, fasciculation, elevated serum creatine kinase (CK) or significant electrophysiological data. Cases of HAM/TSP complicated with polymyositis or motor neuron disease have been reported. But no investigation has been directed to muscular pathology in many patients of HAM/TSP. We conducted muscle biopsies on 13 HAM patients. Four patients showed neurogenic changes. Six patients showed histological findings indicative of inflammatory myopathy. We investigated surface marker of invading cells in these 6 patients. In all patients, T lymphocytes were more predominant than B lymphocytes and in three of them T helper/inducer cells were more predominant than T suppressor cells. In 2 patients, only slight myopathic change could be seen, such as variation in fiber diameter and increase in the number of internal nuclei. In 1 patient, type 2 fiber atrophy was seen, and was possibly the result of disuse. Disturbance of secondary motor neurons or inflammatory myopathy is thus shown to be possibly associated with HAM/TSP.

Adult↗
PubMed1992

Muscular involvement in lysosomal acid lipase deficiency in rats.

We investigated the pathological and biochemical changes of skeletal muscle in rats with lysosomal acid lipase deficiency, which is an animal counterpart of human Wolman's disease. In the affected rats, the acid lipase activity for three different substrates, 4-methylumbelliferyl-oleate (18.9% of the normal control level), [14C]cholesteryl oleate (23.5%), and [14C]triolein (26.9%), was similarly decreased in the lysosomal fraction of skeletal muscle which was obtained by differential centrifugation. Histochemical studies showed that acid phosphatase activity was high in the endomysium and perimysium and in some muscle fibers. Some fibers showed vacuolar degeneration resembling "rimmed vacuoles". Ultrastructural studies demonstrated many membrane-bound lipid droplets in the muscle fibers, especially in the subsarcolemmal space, indicating that a low density lipoprotein (LDL) uptake pathway apparently existed in the muscle cells. However, such lipid accumulation was much greater in the interstitial cells and the endothelial cells. This distribution also suggests that LDL/cholesterol is supplied to muscle cells predominantly through endothelial cells.

Animals↗
PubMed1992

Experimental simvastatin-induced myopathy in rabbits.

We induced experimental myopathy in rabbits by giving simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. After oral administration of simvastatin (50 mg/kg/day) for 2 weeks, serum CK was elevated in 5 of 7 rabbits; degenerating or necrotic fibers were seen in 3 rabbits. Using electromyography, myotonic discharges were found in the 2 rabbits examined. The combination of myotonic discharges, necrosis and raised serum CK levels suggests that the myopathy was induced by lesions of the muscle surface membrane.

Administration, Oral↗
PubMed1992

Cell surface phenotype of in vitro proliferating lymphocytes in HTLV-I-associated myelopathy (HAM/TSP).

The in vitro proliferation of peripheral blood lymphocytes (PBLs) without any mitogenic stimulation is one of the hallmarks of human T lymphotropic virus type I (HTLV-I) infection. Recent evidence suggests a difference in the degree of the phenomenon between HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-I carriers (AC). In this article, we demonstrated several alterations in the features of the in vitro transformed lymphocytes between patients with HAM/TSP (n = 16) and AC (n = 8). The percentages of total CD8+ and CD8+CD28+ cells were significantly increased in the in vitro proliferating T lymphocytes derived from the patients with HAM/TSP when compared to those from AC. HAM/TSP was segregated from AC by the high degree of the proliferation of CD8+CD28+ cells. The expression of HTLV-I-specific antigens on the cultured PBLs was detected only in the subjects which showed low CD8+CD28+/CD4+ ratio of the in vitro proliferating lymphocytes. These findings suggest that this phenomenon distinguishes HAM/TSP from AC, not only in quantity but also in quality.

Adult↗
PubMed1992

Mimicry between HTLV-I and myelin basic protein: no response in HTLV-I-associated myelopathy patients.

The reactivity to a peptide from the HTLV-I polyprotein (FKLPGLNSR) and a similar sequence from myelin basic protein (MBP) (FKLGGRDSR) was examined in relation to the proposal that mimicry of MBP by HTLV-I could be involved in autoimmune responses in HTLV-I-associated myelopathy (HAM). It was found that rabbit antibodies raised against the HTLV-I peptide recognised both peptides, with a titre of 1/10240 to the HTLV-I peptide and 1/5220 to the MBP peptide. Human sera from HAM patients and a HTLV-I carrier without HAM showed slightly higher responses to the HTLV-I peptide compared to the responses from uninfected human sera. HAM patients had greater responses to the HTLV-I peptide than to the similar MBP peptide and an unrelated bovine MBP peptide. There was no recognition of the peptides by peripheral blood lymphocytes from HAM patients or a HTLV-I carrier without HAM. It was concluded that although cross-reactivity was demonstrated in rabbits and the HTLV-I peptide was recognised by sera from HAM patients, the epitope does not appear to evoke a mimicking response to the similar region in MBP. Hence it is not likely to be involved in the pathogenesis of HAM through molecular mimicry.

Amino Acid Sequence↗
PubMed1992

Geographical subtypes demonstrated by RFLP following PCR in the LTR region of HTLV-I.

It has been demonstrated that specific mutations, localized in the long terminal repeat (LTR) region of HTLV-I, allowed to propose the existence of three HTLV-I subtypes. Because some of these mutations created or suppressed the restriction sites for ApaI, NdeI, DraI, SacI, MaeIII, and MaeII enzymes, these endonucleases were used for characterization of further 30 HTLV-I isolates. Seventeen proviral DNA from Japan, five from the Caribbean, one each from French Guyana, the United States, and China, two from Ivory Coast, and three from Zaire were tested. The DNA used were extracted from 26 in vivo peripheral blood mononuclear cell samples and from four cell lines obtained from two Japanese, one Chinese, and one North American patients. Digestions were performed on amplified DNA of the LTR region (nucleotides 31-768). The results confirm the existence of three subtypes of HTLV-I according to LTR sequences. Subtype I was observed only in patients from the Ivory Coast and Zaire. Subtype II was found in the patient from the French West Indies, and in 33% of the samples from Japan. Subtype III was most often observed in the Japanese but also in the Zairian patients.

Adult↗
PubMed1992

Patients with homocystinuria: high metal concentrations in hair, blood and urine.

Patients with homocystinuria excrete a large amount of metal in their urine. Homocysteine similar to penicillamine, administration to methylmercury treated rats resulted in a large amount of urinary methylmercury excretion. These results suggested that the total metal amounts in the whole body of patients with homocystinuria might be decreased. However, actually metal concentrations in hair and plasma of these patients were higher than those of normal controls. High plasma and hair metal levels are not accounted for in patients with homocystinuria. The physiological metal excretory mechanism in which small amounts of metals bind to the small, plasma molecular substances filter through the kidney and emerge in the urine is necessary for reconfirmation. Strongly perturbed metal metabolism exists in the patients with homocystinuria.

Adult↗
PubMed1992

Target epitope in the Tax protein of human T-cell leukemia virus type I recognized by class I major histocompatibility complex-restricted cytotoxic T cells.

A trans-acting regulatory gene product p40tax (Tax) of human T-cell leukemia virus type I (HTLV-I) is one of the main target antigens recognized by cytotoxic T lymphocytes (CTL) specific for HTLV-I. A CTL epitope within the Tax protein was identified in this report. HTLV-I-specific CD8+ CTL lines established from two HTLV-I carriers with HTLV-I-associated myelopathy or Sjögren syndrome were previously demonstrated to kill predominantly the target cells expressing HTLV-I Tax. The CTL from two patients showed significant levels of cytotoxicity to autologous target cells pulsed with a synthetic peptide of 24 amino acids corresponding to the amino-terminal sequences of the Tax protein. Allogeneic target cells were also sensitized for CTL by this peptide when the target cells have HLA-A2. Tax-specific cytotoxicity, detected as cytolysis of the target cells infected with vaccinia virus-HTLV-I recombinant expressing Tax protein, was almost completely inhibited by competitor cells pulsed with the synthetic peptide. This indicates that a major CTL epitope is present in this peptide. Further analysis using shorter peptides revealed that the core sequence of the CTL epitope was LLFGYPVYV at positions 11 through 19. This sequence can be aligned with the HLA-A2-specific motifs reported recently.

Amino Acid Sequence↗
PubMed1992

Electrophysiological studies in cerebrotendinous xanthomatosis.

Seven patients with cerebrotendinous xanthomatosis (CTX) were studied by electrophysiological techniques. The percentages of abnormalities detected in nerve conduction studies and electroencephalograms were 28.6% (two patients) and 100%, respectively. All patients showed prolonged central conduction times in short latency somatosensory evoked potentials (SSEPs) by tibial nerve stimulation but normal SSEPs by median nerve stimulation. Brain stem auditory evoked potentials and visual evoked potentials were abnormal in three (42.9%) and four patients (57.1%), respectively. These electrophysiological parameters were correlated with the ratio of serum cholestanol to cholesterol concentration. The results of SSEPs suggest that the polyneuropathy in CTX is caused by distal axonopathy affecting longer axons before shorter axons (central-peripheral distal axonopathy).

Adult↗
PubMed1992

Changes in serum lipoprotein(a) and C4b-binding protein levels after acute myocardial infarction.

We investigated changes in serum lipoprotein(a) (Lp(a)) and C4b-binding protein (C4bp) levels following acute myocardial infarction (AMI). Serum lipids, apolipoproteins, C-reactive protein (CRP), sialic acid and haptoglobin (Hp) were also measured and evaluated. The study involved 16 patients (11 men, 5 women, mean age 68.2 +/- 8.4 years) with AMI admitted within 12 h after the onset of illness. CRP rose sharply and immediately after the onset of AMI, reaching its maximum level on the 3rd day of illness. This was followed by temporary increases in sialic acid and Hp, both of which peaked on the 7th day of illness. The Apo A-I level was significantly lower on the 14th day, while the Apo B level was significantly lower on the 3rd day. Serum total cholesterol (T-Ch), HDL-Ch and LDL-Ch showed temporary decreases after the onset of illness. Serial examination of the serum of patients with AMI yielded the following findings; 1) Both Lp(a) and C4bp levels rose temporarily with similar patterns of variation, and 2) they took longer time to peak (around the 14th day) and lasted longer than the increases in the other acute reactive proteins.

Aged↗
PubMed1992

Risk factors in normolipidemic male patients with coronary artery disease in Japanese.

We examined serum lipids, lipoproteins, apolipoproteins (Apo), lipoprotein(a) (Lp(a)), C4b-binding protein (C4bp) and lathosterol in 22 normolipidemic (serum total cholesterol less than 220 mg/dl and serum triglycerides less than 150 mg/dl) male patients with coronary artery disease (CAD) and 33 normal male subjects. Many of the patients in the CAD group with normal total cholesterol (T-Ch) and triglycerides (TG) had higher TG, low-density lipoprotein (LDL)-Ch, beta-lipoprotein (Lipo) and Apo B values and lower high-density lipoprotein (HDL)-Ch, Apo A-I and Apo A-II values than those of the control group. Differences were also observed in the beta-Lipo/HDL-Ch, Apo B/Apo A-I, and HDL-Ch ratios and the atherogenic index [A.I. = (T-Ch--HDL-Ch)/HDL-Ch], all of which are generally accepted as indices for atherosclerosis. Even in CAD patients with normolipidemia, the HDL-Ch/T-Ch ratio and A.I. seemed to be important risk factors. In addition, Lp(a) and lathosterol, an accepted indicator of whole-body cholesterol synthesis, were higher in the CAD group. The CAD group also appeared to have a higher C4bp value, suggesting that this parameter is correlated with other lipids.

Carrier Proteins↗