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The isozyme patterns of leukocyte α-d-mannosidase in two sisters with mannosidosis, their parents and a patient with trisomy 19 were studied. The isozyme pattern of liver mannosidase of a normal subject was also studied. In the patients with mannosidosis the neutral isozyme (isozyme C or fraction C) was present, but the acidic isozymes (isozyme A and B or fraction A and B) were not detectable. In their parents the activity of the acidic isozymes was one-third of the normal activity. These findings suggest that the patients are homozygous and their parents are heterozygous in terms of deficiency of acidic isozymes. In the patients with trisomy 19, the activity of α-d-mannosidase was 4.9 times the upper limit of the normal value, while the levels of other lysozomal enzymes were normal. This increase was mainly due to increases of the A and B isozymes of mannosidase. This finding suggests that the gene encoding acidic isozymes, but not that encoding the neutral isozyme, is located on chromosome 19. The isozyme pattern of α-d-mannosidase differed in different tissues of normal subjects, and the difference in severity of lesions in different organs of the patients with mannosidosis could be explained by differences in the isozyme patterns of the enzyme in these organs.

A counterimmunoelectrophoresis technique for detection of serum myoglobin (Mb) was improved using non-ionic polymer dextran. Precipitin lines were graded according to their strength, which was ascertained by radioimmunoassay data. By this method, serum Mb in concentrations of 500 ng./ml. before stain and of 200 ng./ml. after stain were detected. Electrophoretic time was 60 minutes. Among 32 cases of acute myocardial infarction (AMI) whose blood samples were collected within 24 hours after disease onset, precipitin lines were detected in 25 cases (78 per cent) before stain and 31 cases (97 per cent) after stain. Considering the early peak concentration time (approximately 10 hours) of serum Mb after AMI onset, diagnosis becomes more rapid and exact with this method, especially in severe cases.

Fetal hemoglobin (HbF) levels determined in healthy Japanese adults ranged from 0.3% to 16.0% as F cells and 0.17% to 2.28% as HbF content, which were the same as those obtained in other countries. The frequency distribution of 300 healthy adults with various numbers of F cells consisted statistically of two different groups, low and high F-cell groups. Individuals with greater than or equal to 4.4% of F cells (HbF about 0.7%) were defined as the high F-cell trait, which accounted for 11.3% of males and 20.7% of females. Family studies of 21 probands with this trait and sex-different frequency analyses in the population and probands revealed X-linked dominant inheritance. Two other families of the trait associated with color blindness were described, although no definitive evidence for linkage was obtained between the two. A review of population and family studies reported in the literature indicated that persons with Swiss-type hereditary persistence of fetal hemoglobin (HPFH) are of the same kind as this trait in their incidence and inheritance form, but represent a portion of the trait with higher levels of HbF or F cells. The existence of X chromosome-localized regulatory gene(s) for the developmental switch of human Hb production is discussed.

The activities of serine protease in muscles from normal persons and from patients with progressive muscular and neuromuscular diseases have been determined. A significant increase in the level of serine protease was found in muscle of patients with Duchenne-type muscular dystrophy and with Becker-type muscular dystrophy, but the activity was not increased in muscle of a patient with amyotrophic lateral sclerosis.

In the present study we sought to determine the presence of myoglobin in human thyroid tissue. When reacted with antihuman myoglobin antibody on the Ouchterlony plate, homogenates of human thyroid tissue formed a precipitation line. When the human thyroid extract was included in human myoglobin RIA, the dilution curve of thyroid extract was parallel to the standard curve of myoglobin. When the myoglobin immunoreactivity in thyroid extract was fractionated with Sephadex G 75 column, the immunoreactivity was eluted in a peak identical with authentic myoglobin. The position of the peak was different from that of thyroglobulin. Myoglobin concentration in thyroid tissue was estimated to be 0.7-110 mg/g wet wt, being about 1/6000 to 1/40 of that in skeletal muscle. Histochemical studies demonstrated the presence of myoglobin immunoreactivity in thyroid tissue, especially in the apical border of thyroid epithelial cells, implying a functional role in iodinating process or exocytotic-endocytotic process.

A sensitive sandwich enzyme immunoassay (EIA) for human myoglobin (Mb) was developed. Serum Mb was assayed by incubation with an anti-Mb rabbit IgG-coated polystyrene ball and then with affinity-purified anti-Mb Fab'-horseradish peroxidase (HRP) conjugate. The HRP activity bound to the polystyrene ball was assayed fluorimetrically. The sensitivity was 3.1 pg/tube and serum Mb levels of 0.4-1000 micrograms/l could be determined. The recoveries of Mb added to human sera at 3 concentrations were 92.8-99.8%. The within- and between-assay coefficients of variations (CV values) were both below 10%. The regression equation of values determined by EIA and radioimmunoassay (RIA) was y(EIA) = 0.964x (RIA)--2.30 and the correlation coefficient was 0.984. The mean normal serum concentration of Mb was 21.5 +/- 6.0 micrograms/l (mean +/- SD) in males and 16.9 +/- 5.8 micrograms/l in females. The significance of serum Mb determination by the EIA in various diseases was confirmed. The present EIA for Mb is more sensitive and economical than RIA and should be useful for determining Mb in biological materials.

The localization of myoglobin in human skeletal muscle cell was studied by immunoelectron microscopy. The Fab'-horseradish peroxidase (HRP) conjugate was prepared by the maleimide method recently developed by Ishikawa et al. This method gave better recovery and less polymerization of HRP than the periodate method. By the direct immunoperoxidase method using this conjugate, myoglobin was shown to be localized in the I-band region of skeletal muscle cells. The outer membrane of mitochondria and triads stained intensely, but A-bands were not stained. Myonuclei and intermyofibrillar spaces were also not stained. The localization of myoglobin in the I-band implies its function in energy generation.

To estimate the replication of the human T-cell leukemia virus type I (HTLV-I) in patients with HTLV-I-associated myelopathy (HAM), or tropical spastic paraparesis (TSP), HTLV-I DNA integrated into lymphocyte genomes was analyzed by Southern blot hybridization. HTLV-I DNA was detected in 125 (82%) of 153 patients and most showed random integration. This incidence was much higher than the 29% found in asymptomatic carriers. Therefore, HAM/TSP development is associated with a high level of HTLV-I replication. In addition, lymphocytes from 3 patients with HAM/TSP showed monoclonal integration of HTLV-I DNA, indicating adult T-cell leukemia.

常染色体優性の遺伝性を示す家族性特発性大脳基底核石灰化症(FIBGC)の1家系3症例を報告した.発端者16才,女性で, 12才時に拍動性の頭痛を訴えるようになり, 16才で軽度の小脳性運動失調を認めた.そして,頭部X線像および頭部CT像で両側の大脳基底核部と視床に石灰化像を認めた.不随意運動や筋緊張の異常はなく,副甲状腺機能も正常であった.母と母方祖父にも大脳基底核の石灰化像がみられたが,神経症状はみられなかった.本家系では石灰化像の軽い若年の発端者にのみ神経症状が出現しているのが特徴であり,従来のFIBGCの報告例と異なっている.また,錐体外路症状はなく,基底核部石灰化による神経障害は少ないと考えられた.

A new type of progressive muscular dystrophy, autosomal recessive distal muscular dystrophy, is described, based on observations on 17 cases (8 males and 9 females) in 8 families, including an autopsied case. The disease developed in young adults. Muscle weakness and atrophy were most marked in the distal parts of the legs, especially in the gastrocnemius and soleus muscles, and then spread to the thighs and gluteal muscles. Early impairment of standing on tip-toe with retention of the ability to stand on the heels was conspicuous. Difficulty in climbing stairs, standing up and walking subsequently appeared, but rarely progressed to confinement to bed. The forearms became mildly atrophic, with decrease in grip strength, but the small hand muscles were spared. The EMG showed myopathic changes and nerve conduction was normal. Serum creatine kinase activity was characteristically increased up to 100-fold in the early stages of the disease. It was also markedly increased in subjects in the preclinical stage and mildly in some heterozygotes. Muscle biopsies revealed myopathic changes with severe segmental necrosis accompanied by regeneration. The changes were similar to those of Duchenne muscular dystrophy. An autopsied case, aged 68 years, showed generalized muscle abnormalities with a distal predominance. The muscles in the lower legs, especially those of the calves, were severely affected. No lesions were found in the brain, spinal cord or peripheral nerves.

Human metmyoglobin was separated electrophoretically into four subfractions: Mb(1), Mb(2), Mb(3), and Mb(4), which divide into at least two biochemically independent groups: Mb(1) and Mb(2), and Mb(3), and Mb(4). In normal subjects, Mb(1) constituted the predominant component; Mb(2), Mb(3), and Mb(4) were the minor components in this descending order. In the Duchenne type of progressive muscular dystrophy, on the contrary, a remarkable decrease in Mb(1) and a concomitant increase in Mb(3) were observed. This unique abnormality in the relative distribution of myoglobin subfractions was recognized only in the Duchenne type and not in other types of progressive muscular dystrophy or in other myopathies.

We report a 42-year-old Japanese woman with HTLV-I-associated myelopathy (HAM) combined with adult T-cell leukemia (ATL). Combination of the 2 diseases has been extremely rare. The infrequency is explained by HLA types unique to each disease. Our patient suggests that the HAM-associated HLA haplotype does not prevent the development of ATL.