Localization of the pathogenic gene of Behçet's disease by microsatellite analysis of three different populations.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS: The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, PC: = 0.000014; Greek, PC: = 0. 00047; Italian, PC: = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, PC: = 0.000000000017; Greek, PC: = 0.00000032; Italian, PC: = 0. 0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51. CONCLUSIONS: These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.

MICA gene polymorphisms and HLA-B27 subtypes in Japanese patients with HLA-B27-associated acute anterior uveitis.

PURPOSE: HLA-B27-associated acute anterior uveitis (HLA-B27 AAU) seems to be triggered by external factors in persons with a particular genetic background. It is still uncertain whether HLA-B27 or other gene(s) near the HLA-B region predisposes to uveitis in a linkage disequilibrium with B27. The authors investigated microsatellite polymorphism within the transmembrane region of the MICA gene, located 47 kb centromeric of the HLA-B gene, and HLA-B27 subtypes. METHODS: Seventeen HLA-B27-positive Japanese patients with HLA-B27 AAU, 51 Japanese controls, and 20 B27-positive Japanese controls were examined for MICA gene polymorphism within the transmembrane region using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. Furthermore, B27-positive patients with HLA-B27 AAU and B27-positive controls were examined for HLA-B27 subtypes by the PCR-sequence-specific primer method. RESULTS: The microsatellite allele in the MICA gene, consisting of four repetitions of GCT/AGC (designated A4 allele), was present at a significantly higher phenotype frequency in the patient group (64.7%) than in the control group (25.5%) (chi 2 = 6.95, Pc = 0.042). Furthermore, the frequency of the A4 allele was significantly higher, even when compared with 20% in the B27-positive control group (chi 2 = 5.88, Pc = 0.042). The frequency of HLA-B27 subtypes was not significantly different between B27-positive patients with HLA-B27 AAU and B27-positive controls. CONCLUSIONS: These results suggest that the MICA gene itself, or other nearby gene(s), linked to the MICA A4 allele may be involved in the development of HLA-B27 AAU and that HLA-B27 subtypes are not important in the development of HLA-B27 AAU in a Japanese population.

Association of MICA gene and HLA-B*5101 with Behçet's disease in Greece.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many different ethnic groups. Recently MICA, a member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), was identified near the HLA-B gene, and a triplet repeat microsatellite polymorphism was found in the transmembrane (TM) region. Because a strong association with BD of one particular MICA-TM allele, A6, was shown in a Japanese population, the present study was conducted to investigate microsatellite polymorphism in Greek patients with BD to know whether this association is generally observed in BD occurring in other populations. METHODS: Thirty-eight Greek patients with BD and 40 ethnically matched control subjects were examined for MICA microsatellite polymorphism using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Similar to the Japanese patients with BD, the phenotype frequency of the MICA-TM A6 allele was significantly increased in the Greek patients with BD (50.0% in control subjects versus 86.8% in BD cases), with an odds ratio (OR) of 6.60 (P = 0.0012). The MICA-A6 allele was found in a high frequency both in males and females (weighted OR = 6.68; P = 0.0017). No association was found between the A6 allele and several disease features. A strong association exists between the MICA-TM A6 allele and the B*5101 allele in both the control subjects and patients with BD (weighted OR = 44.39; P = 0.0000023). CONCLUSIONS: This study revealed in Greek patients a strong association of BD with a particular MICA-TM allele, MICA-A6, providing insight into the molecular mechanism underlying the development of BD.

Microsatellite polymorphism within the MICB gene among Japanese patients with Behçet's disease.

Behçet's disease (BD) is known to be associated with HLA-B51. In order to investigate the influence of the MICB gene, located about 120 kb centromeric of the HLA-B gene, on the susceptibility to BD, (CA/TG) dinucleotide repeat microsatellite polymorphism in intron 1 of the MICB gene was investigated among 77 Japanese patients with BD, 60 randomly selected controls and 28 HLA-B51-positive unrelated healthy controls. There was no significant difference in the phenotype frequency of the microsatellite polymorphism between the BD patients and controls. This result suggests that the MICB gene itself is not responsible for the development of BD, and that the candidate gene(s) for BD is located between the MICA and HLA-C genes.

Triplet repeat polymorphism in the MICA gene in HLA-B27 positive and negative caucasian patients with ankylosing spondylitis.

Previously, we reported a triplet repeat polymorphism in the transmembrane region within the MICA gene closely linked to HLA-B in a limited number of B27-positive Caucasian patients with ankylosing spondylitis (AS) (N = 48). In this study, we enrolled much more patients including some negative for B27, 162 AS subjects consisting of 140 B27-positive, and 22 B27-negative patients. The microsatellite allele consisting of 4 repetitions of (GCT/AGC) (A4 allele) was present at a significantly higher phenotype frequency in the patient group than in the ethnically matched control group (Pc < 0.000001). However, the frequency of the A4 allele was not significantly higher in the B27-positive and B27-negative patient groups, as compared to the B27-positive and B27-negative control groups, respectively. The higher phenotype frequency of the A4 allele in the patient group was supposed to be due to a strong linkage disequilibrium between the MICA and HLA-B genes. Thus, the possibility that the MICA gene is involved in the pathogenesis of AS can be excluded, supporting the hypothesis of a primary association of AS with HLA-B27.

Microsatellite mapping of a susceptible locus within the HLA region for Behçet's disease using Jordanian patients.

Behçet's disease (BD) has been established to be associated with HLA-B51. However, it has not been revealed whether the HLA-B51 gene itself or another gene located near the HLA-B gene is directly involved in the pathogenesis of BD. Previously, using Japanese BD patients, our group has narrowed down a BD-causative gene to 46 kb between the MICA and HLA-B genes by means of fine mapping analysis with eight microsatellite markers distributed within a 1100 kb segment around the HLA-B gene. To know whether this mapping result is generally observed in BD of another population we have investigated repeat polymorphisms of the same microsatellite markers in Jordanian BD patients. Furthermore, we have evaluated these data by Mantel-Haenzel stratified analysis to find out a primarily associated locus for BD. As a result, HLA-B51 was found to be the most strongly and primarily associated marker. This result suggests that the pathogenic gene of BD is HLA-B51 itself, but unlikely to be other genes located in the vicinity of HLA-B.

Association between MICA gene A4 allele and acute anterior uveitis in white patients with and without HLA-B27.

PURPOSE: Acute anterior uveitis is strongly associated with the HLA-B27 antigen and triggered by the involvement of some external factors. However, it is uncertain whether HLA-B27 itself or other gene(s) near the HLA-B region in a linkage disequilibrium with HLA-B27 predispose to this uveitis. We therefore investigated microsatellite polymorphism in the transmembrane region of the major histocompatibility complex class I chain-related gene A (MICA), located 47 kilobases (kb) on the centromeric side of the HLA-B gene on the short arm of chromosome 6 within 6p21.3. METHODS: We examined the following patients for MICA gene polymorphism by means of polymerase chain reaction and subsequent automated fragment detection by fluorescent-based technology: 64 (37 HLA-B27-positive and 27 HLA-B27-negative) whites with acute anterior uveitis, 74 (67 HLA-B27-negative and 7 HLA-B27-positive) ethnically matched random controls, and 36 HLA-B27-positive healthy controls. RESULTS: The microsatellite allele consisting of four repetitions of GCT/AGC (designated A4 allele) was present at the significantly higher phenotype frequency (71.9%) in the patient group than in the ethnically matched random control group (13.5%) (P < .0000001, corrected P < .0000001). The A4 allele was strongly linked to HLA-B27 in a white population. However, the A4 allele was also found at the significantly higher phenotype frequency (37.0%) even in the HLA-B27-negative patient group than in the ethnically matched HLA-B27-negative control group (4.5%) (P = .0086, corrected P = .043). CONCLUSIONS: These results suggest that the MICA gene itself or other nearby gene(s) linked to the MICA A4 allele may be involved in the development of acute anterior uveitis in a white population.

Cystic lymphangiomas of the colon.

We report a patient with cystic lymphangiomas diagnosed by endoscopic ultrasonography and resected by partial polypectomy. A 42-year-old woman consulted a nearby physician because of a positive fecal occult blood test. Barium enema and colonoscopy revealed the presence of abnormalities. On March 11, 1997, she was admitted to our department for further evaluation and treatment. A barium enema examination revealed two protruding lesions in the transverse colon. Colonoscopy showed a teardrop-type mass in the left side of the transverse colon. The mass was cushion-sign positive, and its shape readily changed on respiration and with changes in body position. Another superficial smooth mass was found in the right side of the transverse colon. Ultrasonography of the colon confirmed the presence of a submucosal mass showing a cyst-like pattern. Cystic lymphangiomas were diagnosed and resected endoscopically. Histopathological examination revealed markedly dilated ducts consisting of a single layer of endothelial cells in the submucosa of the colon. The diagnosis was cystic lymphangioma.

Urinary calcium and calcium balance in young women affected by high protein diet of soy protein isolate and adding sulfur-containing amino acids and/or potassium.

The effects of sulfur-containing amino acids (SAA) and potassium (K) on urinary excretion and retention of calcium (Ca) of 27 young Japanese women were studied. A basal diet low in protein level (50 g per day) was fortified by meat or soy protein isolate (SPI) to a protein level of 100 g per day, and effects of addition of apple to these high protein diets, and addition of SAA and/or potassium (K) to the high SPI diet, especially on urinary Ca excretion, were studied. The addition of meat which increased protein intake to 100 g caused the increase in apparent absorption and urinary excretion of Ca with increased excretion of urinary sulfur (S), phosphate, ammonia, and titratable acids (TA), whereas addition of SPI did not. The addition of apple to high meat diet decreased absorption and urinary excretion of Ca. Urinary Ca, S, K, ammonia, and TA excretion increased by the addition of SAA to high SPI diet in a manner similar to the meat diet. Consequently, SAA-supplemented diet had a significantly negative effect on Ca retention. In SPI+SAA,K diet period, urinary K excretion markedly increased, and increments in urinary Ca, ammonia, and TA excretion were reversed. These changes observed in SPI+SAA, K diet period were similar to those by adding apple to meat diet without any effect on Ca absorption. The results suggest that the hypercalciuria induced by high meat diet is mainly caused by high content of SAA and may be reversed by the ingestion of K-rich foodstuffs, and soy protein does not induce hypercalciuria because of it contains less SAA than animal protein.

Carbon dioxide and oxygen budgets of a plant cultural system in a CELSS--a case of cultivation of lettuce and turnips.

In order to collect basic data about CO2 and O2 budgets of a plant cultural system in a CELSS, the variation of the CO2 absorption rates of lettuce and turnips were observed during the growing period, under different conditions. The O2 release rates were deduced from the CO2 absorption rates multiplied by 32/44. As a result, when the light intensity, the photoperiod and the atmospheric CO2 concentration increased, the rates also increased. The effects on the turnips were more significant than those on the lettuce. Turnips at 310 micromoles/m2/s of PPFD, 24 hours of photoperiod and 1100 ppm of CO2 concentration grew most actively in the present experimental conditions. One turnip absorbed 32.3 g CO2 and released 23.5 g O2 for 6 days between 24 days and 30 days after sowing.

Episcleritis associated with pigmentary retinal degeneration in an HTLV-I carrier.

Human T-cell lymphotropic virus type I (HTLV-I) has been reported as the cause of a kind of endogenous uveitis (HTLV-I associated uveitis; HAU). We observed a case of episcleritis in a HTLV-I carrier with pigmentary retinal degeneration. HTLV-I infection might be associated with the development of episcleritis and pigmentary retinal degeneration. Patients with episcleritis or pigmentary retinal degeneration should be examined for HTLV-I infection.

[Treatment of patients with hepatoma and esophageal varices].

Fifty-nine patients with hepatoma associated with advanced esophageal varices who received a variety of therapeutic modalities in the past 10 years at our department were reviewed. Our therapeutic modalities are hepatic resection, hepatic artery ligation (HAL) and trans-arterial embolization (TAE) for those with hepatoma and non-shunting treatment (NST; esophageal transection or Hassab's procedure) and endoscopic sclerotherapy (ST) for those with esophageal varices. A patient selection was made by our own criterial developed by a multiple regression analysis for the hepatoma and KICG value for esophageal varices. Out of 59.16 underwent hepatic resection and NST. Eight survived more than 2 years. The longest survivor has been living for 4 yr and 4 months. Two-year survival rate is 69.8%. Another 16 underwent HAL and NST. Two-year survival was 14.6%. Another 7 underwent ST following hepatic resection or HAL. Five of the 7 received an emergency ST. Hemostasis was achieved in all of them. Two-year survival was 21.8%. The remaining 20 underwent ST and TAE; 13 received an emergency ST with 85% of hemostasis rate. None of them survived more than 2 years. From these data, it is suggested that a proper selection of patients for a proper therapeutic modality improves the prognosis even in those with hepatoma associated with advanced esophageal varices.