Takehiko Sakurami

The prevalence of human T-cell leukemia virus type I infection in patients with hematologic and nonhematologic diseases in an adult T-cell leukemia-endemic area of Japan

In order to clarify the prevalence of human T‐cell leukemia virus type I (HTLV‐I) infection in the Kagoshima district, Japan, a highly endemic area for HTLV‐I, antibodies for HTLV‐I (anti‐HTLV‐I) were examined in the sera of 6167 from healthy residents and patients with various hematologic and nonhematologic diseases. In healthy residents, including blood donors, the prevalence of anti‐HTLV‐I was 11.9% (562/4741 persons). The prevalence increased with age, and was significantly higher in females than in males (P < 0.01). The prevalence of anti‐HTLV‐I in blood donors was 8.5%. In hematologic diseases, the prevalence of anti‐HTLV‐I was 98.3% in ATL, 28.9% in lymphoproliferative disorders except ATL, and 10.6% in myeloproliferative disorders. In nonhematologic diseases, the prevalence of anti‐HTLV‐I was shown to be 29.5% in pulmonary tuberculosis, 25.8% in leprosy, 33.8% in chronic renal failure (CRF), 21.9% in autoimmune diseases, and 47.8% in strongyloidiasis. The various diseases except myeloproliferative disorders had significantly higher prevalence of anti‐HTLV‐I than healthy residents (P < 0.01 or 0.05). For autoimmune diseases, the prevalence of anti‐HTLV‐I in patients with blood transfusion (55.6%) was higher than in those without blood transfusion (8.7%), and healthy residents. In hemodialysis patients with CRF who had received blood transfusions the prevalence of anti‐HTLV‐I increased with the number of blood transfusions. Therefore, HTLV‐I transmission via blood transfusion would partially explain these high prevalence of anti‐HTLV‐I. However, the prevalence of anti‐HTLV‐I in hemodialysis patients with CRF was statistically higher than that in healthy residents, regardless of blood transfusion (P < 0.01). Furthermore, hemodialysis patients showed significantly higher prevalence of anti‐HTLV‐I than healthy residents, even at a younger age. Patients with pulmonary tuberculosis and leprosy showed the same results as hemodialysis patients. These results suggest the possibility that HTLV‐I infection has some relation not only to ATL but also to other diseases. Therefore, it seems very important to halt the spread of HTLV‐I transmission as soon as possible.

HLA-DR Specifications in Japanese with Juvenile-onset Insulin-Dependent Diabetes Mellitus

Specific allelic associations vary among ethnic groups. We studied the distribution of HLA-A,-B,-C, and -DR antigens in 34 Japanese juvenile-onset diabetic patients. The focus of our current work was HLS-DR antigens because there have been few studies of Japanese with this disease. A significant increase in the frequency of HLA-DR4 was found in patients but not in unaffected persons: DR4 was found in 56.3% of the patients versus 32.6% of the unaffected persons. However, the negative correlation between DR2 and patients was not statistically significant.

HL-A and hypertrophic cardiomyopathy

HL-A antigens were determined in 26 unrelated Japanese patients with hypertrophic cardiomyopathy. Several antigens were more common in patients compared with controls, but statistically significant differences were not evidenced. We also studied two families in which many had a hypertrophic cardiomyopathy. All the affected individuals revealed HL-A-A9 and B7, while none among the unaffected family members had HL-A-B7. Our findings suggest that the HLA-A system may play some role in the pathogenesis of hypertrophic cardiomyopathy with familial occurrence.

An enzyme-linked immunosorbent assay for immune complex of HTLV-I

A sandwich enzyme-linked immunosorbent assay (ELISA) for immune complexes of human T cell leukemia virus type I (HTLV-I) was developed using monoclonal antibody (MoAb) 3G1 which recognizes a different epitope on HTLV-I to that with which natural human anti-HTLV-I antibody binds. The assay was capable of titrating artificial immune complexes not only at antigen-antibody equivalence but also at antibody excess. Although the antigen-antibody ratios could not be determined in the individual sera from patients with overt ATL, the level of immune complexes in three out of four sera was estimated to be 250 +/- 36 ng/ml. Immune complexes of HTLV-I could not be identified in sera obtained from one patient with overt ATL, three healthy HTLV-I carriers and three normal human controls.

Incidence of Thyroglobulin and Microsomal Antibodies in Normal Subjects

In the course of studies on the occurrence of antithyroid antibodies in various thyroid disorders, serum antibodies to microsome of thyroid epithelial cells, as well as circulating antibodies to thyroglobulin, are demonstrated by tanned red cell hemaggulutination. These thyroglobulin and microsome-coated tanned red blood cells can be efficiently demonstrated with a commercially prepared reagent. (Fuji-Zoki Co.) The sera of 2,350 normal subjects were tested by these thryoid autoantibodies tests. Fifty-one (2.3 per cent) of the sera of 2,350 normal subjects showed a positive reaction for thyroglobulin antibodies, and fifty-nine (2.5 per cent) persons showed a positive reaction for microsomal antibodies. The incidence of thyroglobulin and microsomal antibodies in males and females were progressively greater with age, particularly between ages 60 to 69.

Thyroid Antibodies and Serum Thyrotropin in One Population

Circulating thyroid antibodies are important markers for detecting autoimmune thyroid diseases. A survey was conducted in Daiwa Village, Shimane Prefecture, to determine the incidence of significant asymptomatic autoimmune thyroiditis , in a rural population. One thousand two hundred and forty-two people were examined in the survey. The incidence of overt thyroid disorders was 3/570 males and 12/672 females. Eight were cases of hyperthyroidism and three were diffuse or nodular goiter. Three were postoperative cases of struma, including thyroid cancer, and the other one was that of overt hypothyroid ism. We examined antithyroglobulin antibodies (TG) and thyroid microsomal antibodies (MS), excluding 15 patients with overt thyroid diseases. TG and MS were measured by the tanned red cell hemagglutination technique, using commercially available kits, Thyroid Test and Microsome Test (Fuzi Zoki, Tokyo). Eight of 567 (1.4%) males were positive for TG and 32 (5.6%) were positive for MS. Twenty-five of 660 (3.8%) females were positive for TG and 73 (11.1%) were positive for MS. The incidence of TG and/or MS was higher in females. Age-specific prevalence of antithyroid antibodies gradually increased in those over 40. We examined the serum cholesterol levels in subjects with thyroid autoantibodies and also in controls and we found no statistical significance. The serum TSH levels were also studied. 3.9pU/ml, which was the mean serum TSH level in subjects with thyroid autoantibodies,

[Classification of asymptomatic autoimmune thyroiditis by thyrotropin-releasing hormone loading].

Thyrotropin-releasing hormone loading was performed on 91 patients with asymptomatic autoimmune thyroiditis. Four women had no response to this loading test and had high levels in serum total and free thyroxine (TT4, FT4) and in serum total and free triiodothyronine (TT3, FT3). These patients might be classified as subclinical hyperthyroidism (Group G). Twenty-four patients had normal levels of both basal and peak thyrotropin after loading and were classified as Group I. There were no significant differences between 45 controls (Group C) and Group I patients in serum thyroid hormone levels. Patients with normal basal and high peak levels of thyrotropin were included in Group II. The number of patients in this group was 53. The mean levels of basal and peak thyrotropin were 4.8 microU/ml and 39.6 microU/ml, respectively, and were significantly higher than in Group C and Group I (P less than 0.005). In 10 patients classified as Group III with high levels of both basal and peak thyrotropin, serum concentrations of TT4, FT4 and FT3 were significantly lower than in the other groups (P less than 0.025); however, significant differences in TT3 could not be seen among them. Serum cholesterol levels gradually increased from Group C to Group III. There were significant differences between Group C and Group II (P less than 0.05).

[Immunohistochemical localization of cytoskeletal proteins and thyroglobulin in the follicular cells of Hashimoto's thyroiditis].

Using antisera against three kinds of cytoskeletal proteins (keratin proteins, actin protein and myosin protein) and thyroglobulin, immunoperoxidase staining was performed on the follicular cells of 30 patients with Hashimotos thyroiditis. These patients were subdivided into three types by Woolners classification: 9 patients of lymphoid type (L-type), 12 patients of oxiphilic cell type (O-type), and 9 patients of pronounced epithelial destruction type (P-type). The results obtained were as follows: (1) In three-ninths to seven-twelfths of the patients of O-type and P-type, the cytoskeletal proteins were identified in the epithelial cells forming degenerating or atrophic thyroid follicles. In the patients of L-type, however, the cytoskeletal proteins which form large follicles containing much colloid were not found in the epithelium. (2) In some patients of O-type, keratin proteins were abundantly present in the epithelial cells with squamous cell metaplasia. (3) In the patients of L-type, thyroglobulin was found in most of the epithelium forming large follicles, but it was not found in those forming degenerating or atrophic follicles in the patients of O-type and P-type.

Thyroid autoantibodies, antinuclear factors and HB antigen in various hepatic diseases

最近我が国では抗甲状腺抗体の検出法としてタンニン酸処理赤血球凝集反応を応用したThyroid test,及びMicrosome testがキット化され安定した成績が得られるようになってきた.そこで今回,われわれは正常健康人2,350名を対照とし各種肝疾患患者150名につきThyroid test及びMicrosome testを施行し同時に抗核抗体,HB抗原を検索し,これらの関連について検討した.その結果ルポイド肝炎では他の肝疾患に比し抗甲状腺抗体及び抗核抗体の両方共33.3%と著しく高い陽性率を示した.HB抗原は急性肝炎で35%と最も高い陽性率を示したが抗甲状腺抗体とHB抗原との間には相関する関係は見られず,また明らかな相互離反の傾向も見られなかった.抗甲状腺抗体と抗核抗体との間には明らかに相関する関係が見られた.抗甲状腺抗体は正常健康者と同じく肝疾患全体では男性よりも女性で2倍以上の陽性率を示したが10×28以上の高い抗体価を有する者は1例もなかった.

Thyroglobulin and microsomal antibodies in diabetes mellitus in childhood

The purpose of our study was to determine the incidence of thyroid antibodies in diabetes mellitus in childhood and to discuss the correlation between thyroid antibodies and insulin antibodies. The sera of 50 children with diabetes mellitus and 437 children as disease controls were tested by thyroglobulin and microsome-coated tanned red cell hemagglutination test (Fuji Zoki Co. Tokyo). One of the 50 children with diabetes mellitus (2%) was positive with antithyroglobulin antibodies and eleven (22%) were positive with antimicrosomal antibodies compared to 0.4% and 1.1% respectively in 437 disease controls. To clarify the association of insulin antibodies and thyroid antibodies in diabetes mellitus in childhood, insulin antibodies were demonstrated by using a modified method described by Wright. One of the 33 children with negative insulin antibody (2.8%) was positive with antithyroglobulin antibodies and eight (24%) were positive antimicrosomal antibodies. No evident correlation was observed between antithyroid antibodies and insulin antibodies.