Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFalpha gene and HLA genes.

OBJECTIVE: To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor alpha (TNFalpha) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). METHODS: One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFalpha, HLA-A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. RESULTS: The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFalpha gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFalpha -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). CONCLUSION: The -1,031C/-863A allele and the -857T allele of the TNFalpha gene, both of which are related to high production of tumor necrosis factor alpha, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.

[A study of the factors involved in the onset of senile dementia].

Cohort studies were made regarding 1,300 elderly was born before 1918, who were living in a city of Osaka Prefecture in 1979 and were confirmed not to be demented: the fourth survey made in the 13th year thereafter, 1992, showed the following results: 1. The prevalence of senile dementia of Alzheimer's type (SDAT) increased with age, but that of cerebrovascular dementia (VD) did not. 2. The prevalence of female SDAT was remarkably higher with age. 3. The incidence of senile dementia was 0.92%. 4. The results of multi-variate analysis showed the onset of VD and SDAT to be deeply connected with age, blood pressure, the degree of drinking, salt intake and age, inactive ADL, blood pressure respectively.

Assessment of body composition measured by bioelectrical impedance in children.

Bioelectrical impedance methods have been found to be a valid and reliable way of estimating per cent body fat (%BF) in adults. We applied them to healthy children and compared them with conventional anthropometry methods. One thousand two hundred and sixteen children participated in this study. Impedance and skinfold thickness were measured, and %BF was estimated using these values. Bodyweight and height were measured, and per cent obesity (%OB) and body mass index (BMI) were obtained. The values of %BF by the bioelectrical impedance method (%BFi) were 8.6 +/- 4.0% in the junior male group, 14.2 +/- 2.8% in the junior female group, 7.9 +/- 4.7% in the senior male group and 16.1 +/- 2.9% in the senior female group. The %BFi correlated strongly with skinfold thickness, %OB and BMI. Thus %BFi correlated strongly with variables from conventional methods. It was concluded that it is a reliable way of assessing lipid storage in children.

Streptococcal antibody: as an indicator of tonsillectomy.

The significance of antibody for streptolysin-O concerning tonsillectomy was studied. The results obtained were as follows. 1. The upper limit of ASO titer in 5,121 school children was 250 u and a value of more than 333 u was considered abnormal. But the level of the normal limit was different from year to year. 2. Among 143 cases with a high ASO titer of more than 833 u, only 12 cases had recurrent tonsillitis. There was no correlation between the tonsillar hypertrophy and the height of streptococcal antibodies. 3. There was a correlation between the titers determined by ELISA IgG-ASO and ASO in Todd units (r = 0.69), but there was no agreement between the titers determined by ELISA IgM-ASO and ASO in Todd units. 4. IgM-ASO determined by ELISA showed high levels in cases with early stages of streptococcal infection, focal infection and streptococcal carriers. Cases with high ASO, both IgG- and IgM-subclasses, were considered to have an indicative factor for tonsillectomy.

Antibody titer to group A streptococcal polysaccharide in rheumatic fever and rheumatic heart disease.

Antibody to group A streptococcal polysaccharide (ASP) is the only antibody of cellular components which is now detectable in clinical practice. Streptococcal polysaccharide is known to have cross-immunity with the glycoprotein of human heart tissue, and has been discussed as a pathogenesis of rheumatic carditis and valvular heart disease. In this study, ASP titer was determined by passive hemagglutination technique in patients with rheumatic fever and rheumatic heart disease. ASP titer showed higher levels in these patients compared to control children, but there was no specificity in rheumatic carditis or rheumatic heart disease.

A new latex agglutination test for rapid diagnosis of group A streptococci.

A rapid diagnostic test for group A streptococci from throat swabs (Culturette Brand 10-Min Strep ID test of Marion Inc.) was performed in 210 patients with acute pharyngitis. This agglutination test is based on the extraction of streptococcal polysaccharide by nitrous acid and observe agglutination with anti-polysaccharide-coated latex suspension. There was a 95.2% total agreement with a standard culture method and agglutination test and specificity of 93.4%, sensitivity of 96.0% positive predictive value of 90.5% and negative predictive value of 97.3%. From the results of our study, the agglutination test for group A streptococci is of diagnostic value. This new kit would be most useful in out-patient clinics, especially in a small private medical office without culture facilities.

A new scoring system for diagnosis of streptopharyngitis.

From the clinical signs and symptoms of 145 cases of streptococcal pharyngitis and 126 cases of non-streptococcal pharyngitis, a new scoring system for diagnosis of streptococcal pharyngitis was devised. Efficacy of diagnosis for streptopharyngits by this method was 54% if a case had 5 items, 75% if he had 6 items and 93% if he had more than 7 items respectively.

Clinical significance of anti-streptococcal esterase (ASE) determination in rheumatic fever and other streptococcal diseases.

Streptococcal esterase is known as one of the extracellular products of Group A streptococci. In this paper, an antibody of streptococcal esterase titers in patients with rheumatic fever, acute glomerulonephritis and other streptococcal infections were determined. In cases with acute rheumatic fever and acute glomerulonephritis, ASE titers showed almost the same changes as ASO, ASK and ADN-B. The characteristics of the ASE determination, however, is that small changes in the titers could be detected because the final definition of this titer was determined by photometer.

Annual changes of upper limit of ASO titer in school children.

ASO titers of school children were studied during a period from 1975 to 1981, and the annual difference of this titer was investigated. As reported by many authors, the upper limit of normal ASO titer was 250 units and values of 333 units or more should be considered abnormal in our series of children, because 15 to 20% of the population had an antibody titer of 333 units or more. The upper limit of the normal titer was the highest in 1975 when 19.7% of the children showed more than 500 units, and the lowest in 1980 when 20.1% of the children showed more than 80 units. Thus, there was a six-dilution difference in the normal upper limit between these 2 years. We must consider the annual changes of the normal upper limit of streptococcal antibody titer in order to make an accurate diagnosis.

Significance of anti-deoxyribonuclease-B (ADN-B) determination in clinical practice.

The determination of anti-deoxyribonuclease-B (ADN-B) is very important for the diagnosis of antecedent streptococcal infection because almost all of group A streptococci have this antigen and a strong elevation of the antibody is observed in patients with acute rheumatic fever, acute glomerulonephritis and other streptococcal infections. Moreover, ADN-B titers are elevated in cases with streptococcal skin infection, whereas anti-streptolysin O (ASO) titers are rarely elevated in these cases. So the determination of ADN-B is recommended as the second streptococcal antibody test to ASO detection (manual of WHO). In our study, the upper limits of ADN-B in normal subjects were 1:60 in preschool age, 1:480 in school age and 1:340 in adult age groups. In acute rheumatic fever, ADN-B titers were elevated in 87% of the cases and also 87% of the patients with acute glomerulonephritis had high ADN-B titers. In inactive rheumatic fever, 72% of the patients had high ADN-B titers, while, ASO titers were elevated in only 22% of the cases. In streptococcal carrier states, 39% of the children had high ADN-B titers but ADN-B was positive only 8% in non-carrier children.

Upper limit of normal anti-strepto-polysaccharide (ASP) level and the relationship between ASP and antibodies against extracellular antigens.

Titers of anti-strepto-polysaccharide (ASP), antistreptolysin-O, antistreptokinase and antideoxyribonuclease-B were studied from the sera of 184 healthy school children. The upper limit of normal ASP titers in school children was 1:32 in this study, and titers of 1:64 or more were considered abnormal. The correlation coefficients between ASP and other antibodies against extracellular antigens were r = -0.04 to 0.06, and therefore it can be considered that ASP shows an independent value from other antibodies.