Putative amino acid sequence of HLA-DRB chain contributing to rheumatoid arthritis susceptibility.

The association between HLA-DR4 and rheumatoid arthritis (RA) has been established in many ethnic groups. To clarify the determinant of susceptibility to RA, a polymorphic segment of the HLA-DRB gene was amplified in vitro by polymerase chain reaction and analyzed with oligonucleotide probes specific for the HLA-DR4 DNA sequences. A particular sequence encoding amino acids Gln70-Arg71-Arg72-Ala73-Ala74 showed a strong association with RA (p less than 0.005, relative risk 6.0). This amino acid sequence occurs in the DRB molecules with three RA-associated specificities, DR4/Dw14, DR4/Dw15, and DR1. DR4/Dw4, which is common in Caucasian RA patients, has a strikingly similar amino acid sequence Gln70-Lys71-Arg72-Ala73-Ala74 in terms of polarity and charge profiles. Other RA nonassociated sequences differ from this sequence by at least one amino acid substitution that causes the change of the net charge. The composition of amino acid residues at the positions 70-74 may play a crucial role in the pathogenesis of RA.

[Successful surgical repair of left ventricular free wall rupture after acute myocardial infarction].

Left ventricular free wall rupture (LVFWR) after acute myocardial infarction (AMI) is a fatal complication. We report emergency surgery for 2 blow out cases and 2 oozing cases during the 5-year period from 2003. After percutaneous coronary intervention (PCI), subacute thrombosis (SAT) occurred before operation in 2 oozing cases. To the blow out cases, both percutaneous cardiopulmonary support system (PCPS) and intra-aortic balloon pumping (IABP) were applied. The actively bleeding site was approximated by a large mattress suture with felt strips. To the oozing cases, only IABP was applied, and sutureless technique was used for hemostasis. They all survived the operation

Effects of combined PPARgamma and PPARalpha agonist therapy on reverse cholesterol transport in the Zucker diabetic fatty rat.

AIM: We investigated the effects of the combined therapy of PPARgamma and PPARalpha agonists on HDL metabolism, especially concerning reverse cholesterol transport (RCT), using Zucker diabetic fatty rats (ZDF/Crl-Lepr fa rats) that are the rodent model for type 2 diabetes with obesity, hyperlipidaemia and insulin resistance. METHODS: The ZDF rats were divided into four medicated groups as follows: pioglitazone as a PPARgamma agonist (5 mg/kg/day; P group, n = 6), fenofibrate as a PPARalpha agonist (30 mg/kg/day; F group, n = 6), both these medications (P + F group, n = 6) and no treatment (UNT group, n = 6). Non-diabetic rats (ZDF/GmiCrl-lean, CON group, n = 6) served as controls. We evaluated HDL particle size and messenger RNA (mRNA) levels of the following factors: liver X receptor alpha (L x R alpha), ATP-binding cassette A1 (ABCA1) and ABCG1 which are regulated by PPARs and are related to early stage RCT. RESULTS: The significant increase in HDL particle size was demonstrated in rats of the F and P + F groups, although changes in plasma HDL-cholesterol levels were not significant. In accordance with this finding, mRNA levels of ABCG1 in the liver increased significantly. CONCLUSIONS: These findings suggest the efficacy of combined therapy with PPARgamma and PPARalpha in improving lipid metabolism, partly through the enhanced RCT, and insulin resistance in type 2 diabetes mellitus.

Human histocompatibility leukocyte antigen (HLA) haplotype frequencies estimated from the data on HLA class I, II, and III antigens in 111 Japanese narcoleptics.

In order to deduce the predominant haplotypes in Japanese narcoleptics, we have studied a total of 111 Japanese patients with narcolepsy and six multiple-case families for HLA class I and class II antigens, and for class III HLA-linked complement markers. In Japanese narcoleptics, the most frequent haplotypes were B35-DR2, B15-DR2, and B51-DR2. These haplotypes were rare in normal Japanese population. In contrast, the most frequent haplotype of HLA-DR2 in normal Japanese, A24-C blank-Bw52-C4A*2 B*Q0-BF *S-C2*C-DR2-DQw1, had a decreased frequency to one-third of the normal controls. Haplotypes B35-DR2, B15-DR2, and B51-DR2, which were more frequent among Japanese narcoleptics, were different from the haplotype found more frequently among Caucasoid narcoleptics, A3-Cw7-B7-DR2-DQw1. Haplotype analysis on six families showed that B35-DR2 and other rare haplotypes in normal Japanese were associated with narcolepsy. There were four cases without any signs of narcolepsy among 19 subjects with the disease susceptibility haplotypes. This finding suggests an incomplete penetrance of hypersomnia. Haplotype analysis of family members was also useful for the early detection of the high risk children to narcolepsy.

HLA antigens in Japanese patients with myasthenia gravis.

HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG) were investigated. The frequencies of DR9 and DRw13 were significantly increased in the patients who developed MG before 3 yr of age. The DQw3 antigen was positive for all the patients that developed MG before 15 yr with only one exception. All the examined cases that developed MG before 3 yr (including this DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These HLA frequencies decreased as the age of onset increased, and no significant association was observed in adult-onset MG. No patients had B8, DR3, and DQw2. The relative risk was higher for the DR9/DRw13 heterozygotes (37.4) than for DR9 (16.4) or DRw13 (7.1) in the childhood-onset MG. Statistical analysis suggested that DR9 and DRw13 (or DQw1 and DQw3) act synergistically in the disease development. Family study revealed diverse DR9 haplotypes. The most frequent DRw13 haplotype was Bw44-BFF-C4A3B1-DRw13-DQw1, which may be evolutionarily related to the caucasian B8-DR3-DQw2 haplotype. These results showed that MG in early childhood in Japanese individuals is genetically different from that in adulthood and that in caucasians.

Hypertrophy of the extra-articular tendon of the long head of biceps correlates with the location and size of a rotator cuff tear.

AIMS: The aim of this study was to assess hypertrophy of the extra-articular tendon of the long head of biceps (LHB) in patients with a rotator cuff tear. PATIENTS AND METHODS: The study involved 638 shoulders in 334 patients (175 men, 159 women, mean age 62.6 years; 25 to 81) with unilateral symptomatic rotator cuff tears. The cross-sectional area (CSA) of the LHB tendon in the bicipital groove was measured pre-operatively in both shoulders using ultrasound. There were 154 asymptomatic rotator cuff tears in the contralateral shoulder. Comparisons were made between those with a symptomatic tear, an asymptomatic tear and those with no rotator cuff tear. In the affected shoulders, the CSAs were compared in relation to the location and size of the rotator cuff tear. RESULTS: The mean CSA was 21.0 mm2 (4 to 71) in those with a symptomatic rotator cuff tear, 19.9 mm2 (4 to 75) in those with an asymptomatic rotator cuff tear and 14.1 mm2 (5 to 43) in those with no rotator cuff tear. The mean CSA in patients with both symptomatic and asymptomatic rotator cuff tears was significantly larger than in those with no rotator cuff tear (p < 0.001). In the affected shoulders, there were significant differences between patients with more than a medium sized posterosuperior cuff tear and those with an antero-superior cuff tear. CONCLUSION: Regardless of the symptoms, there was significant hypertrophy of the extra-articular LHB tendon in patients with a rotator cuff tear. The values were significantly related to the size of the tear. Cite this article: Bone Joint J 2017;99-B:806-11.

Angiotensin-converting enzyme in diseases of the liver.

Serum angiotensin-converting enzyme activity was measured in various diseases of the liver. Activity increased in progressive order in patients with chronic persistent hepatitis, chronic aggressive hepatitis, and liver cirrhosis. Activity was increased also in patients with acute hepatitis. On the other hand, patients with fatty liver had normal angiotensin-converting enzyme activity and patients with extrahepatic obstructive jaundice showed subnormal activity. Although the mechanism for these enzymatic changes in diseases of the liver remains to be elucidated, serum angiotensin-converting enzyme determination may be useful in the diagnosis of diseases of the liver under certain conditions.

Analysis of human leukocyte antigen HLA-DR beta amino acid sequence in Vogt-Koyanagi-Harada syndrome.

Vogt-Koyanagi-Harada syndrome (VKH) is a systemic disorder involving many organ systems, including the eye, the ear, the skin, and the meninges. One of the important clinical features of the disease is its strong association with histocompatibility antigens HLA-DR4 and HLA-Dw15. To investigate this association at the DNA level, the polymerase chain reaction technique was used. The DR beta 1 DNA sequence was analyzed to determine which part played the most significant role in the disease process. Although the number of patients studied was small, these data showed that these probes were useful in investigating the HLA-DR subtypes related to VKH. All but one patient (19 of 20) had a specific sequence encoding amino acids 70 and 71 of the HLA-DR beta 1 molecule. The data suggest that the sequence that encodes for amino acids 70 and 71 and adjacent ones of the HLA-DR beta 1 molecule could contribute to disease susceptibility.

HLA class II genes in Vogt-Koyanagi-Harada disease.

PURPOSE: Vogt-Koyanagi-Harada disease (VKH) is an autoimmune disorder causing a bilateral diffuse granulomatous uveitis, often with several associated extraocular manifestations. Strong association of human leukocyte antigens (HLA) antigens with the disease has been documented. The details of all HLA class II genotypes were investigated in Japanese patients with VKH to demonstrate the immunogenetic background of the disease. METHODS: Human leukocyte antigen tissue typing was performed in 57 Japanese patients with VKH by the modified two-stage complement-dependent microcytotoxicity method. DNA analyses were done by polymerase chain reaction (PCR)-single-strand conformation polymorphism and PCR-restriction fragment-length polymorphism methods. RESULTS: The frequencies of HLA-DR4 and HLA-DQ4 were 93% and 83% among the patients with VKH, compared with 43% and 32% among the controls, respectively (relative risks, 17.4 and 9.9; Pc < 1.0 x 10(-10)). At the genomic level, all patients had the HLA-DQA1*0301 genotype, which was present in only 67% of the normal controls (relative risk, 56.5; Pc < 1.0 x 10(-5)). With allelic combinations, -DQA1*0301/-DR4 showed the greatest relative risk ratio. Conversely, DQB1*0604 genotype was not detected among the patients. CONCLUSION: It can be postulated that VKH is a disease of combined allelic predisposition in which DQA1*0301 acts as the primary and HLA-DR4 acts as an additive factor in the development of the disease. Based on the negative association of DQB1*0604, we propose that DQB1*0604 provides considerable protection, possibly by altering other factors in the pathogenesis of VKH in the Japanese.

Influence of HLA-DRB1 gene variation on the clinical course of Vogt-Koyanagi-Harada disease.

PURPOSE: To investigate the difference, if any, in the immunogenetic backgrounds between two clinical subtypes of Vogt-Koyanagi-Harada disease (VKH). METHODS: HLA-DR4 gene variations were investigated in 46 Japanese patients, 28 with the prolonged type and 18 with the nonprolonged type of VKH. HLA-DR4 genes were amplified with polymerase chain reaction (PCR) and then analyzed for its variation with single-strand conformation polymorphism (SSCP) and restriction fragment length polymorphism (RFLP) methods. RESULTS: Significant differences were found in the DR4 gene variation in the two clinical subtypes. All the patients with the prolonged type had either the DRB1*0405 or DRB1*0410 variant, whereas 39% of the patients with the nonprolonged type had neither of them. This difference in frequency was statistically highly significant (P = 0.00059, Pc = 0.0041). DRB1*0405 was also more frequent in the prolonged type (93%) than in the nonprolonged type (56%) (P = 0.0044, Pc " 0.030). In the prolonged type, relative risk was highest for DRB1*0405/0410 (128), whereas in the nonprolonged type it was highest for DR4 (8.6). CONCLUSION: This preliminary study showed that DR4 gene variants differed significantly between the two subtypes of VKH, suggesting that the clinical course of VKH is determined partly by the patient's HLA-DR gene variation.