Association of single nucleotide polymorphisms of the interleukin-10 promoter gene and susceptibility to primary biliary cirrhosis: immunogenetic differences in Italian and Japanese patients

Several lines of data suggest that genetic factors play an important role in the onset and/or progression of primary biliary cirrhosis (PBC). Since PBC is an autoimmune disease, it is reasoned to assume that genes encoding cytokines may confer susceptibility to disease. Amongst these factors, interleukin-10 (IL-10) has received significant attention. The promoter region of IL-10 gene has three single nucleotide polymorphisms (SNPs) at positions -1082, -819 and -592. To elucidate the association of the three SNPs of IL-10 promoter region with susceptibility of PBC in two different genetic populations, 159 unrelated patients with PBC (94 Italian and 65 Japanese) and 143 local controls (72 Italian and 71 Japanese) were enrolled. SNPs were determined using allele-specific PCR/RFLP. In Italian PBC patients, the frequency of homozygosity for G/G at position -1082 was significantly higher than that of local controls (p < 0.041, OR = 2.44, 95% C.I.; 1.02-5.86). The frequencies of haplotype GCC in PBC patients, possibly linked to higher IL-10 production, were also significant higher than local controls (p < 0.033). However, in Japanese population, there were no significant differences in the three SNPs and haplotypes between PBC patients and controls. Excessive production of IL-10 may play an important role in some populations in modulating the onset of PBC. Further, immunogenetic studies of PBC should take into account ethnic and geographic variations; this makes such studies in heterogeneous population, like the USA, more difficult.     

Resorbability and solubility of zinc-containing tricalcium phosphate

Using zinc-containing tricalcium phosphate (ZnTCP) as the zinc carrier for zinc-releasing calcium phosphate ceramic implants promoted bone formation around the implants. Because no quantitative information was available on the equilibrium solubility and resorbability of ZnTCP, in vitro equilibrium solubility and in vivo resorbability of ZnTCP were determined and compared quantitatively in this study. The solubility of ZnTCP decreased with increasing zinc content. The negative logarithm of the solubility product (K(sp)) of ZnTCP was expressed as pK(sp) = 28.686 + 1.7414C - 0.42239C(2) + 0.063911C(3) - 0.0051037C(4) + 0.0001595C(5) in air, where C is the zinc content in ZnTCP (mol %). The solubility of ZnTCP containing a nontoxic level of zinc (<0.63 wt %) decreased to 52-92% of the solubility of pure tricalcium phosphate (TCP) in the pH range 5.0-7.4. However, the in vivo resorbed volume of ZnTCP containing the same amount of zinc was much lower than that expected from the in vitro solubility, becoming as low as 26-20% of that of TCP. Cellular resorption of TCP is substantially a process of dissolution in a fluid with an acidic pH that is maintained by the activities of cells. Therefore, the reduction of the resorbability of ZnTCP could be attributable principally to its lowered cellular activation property relative to that associated with pure TCP.     

Neuropeptide Y- and catecholamine-synthesizing enzymes: immunoreactivities in the rat carotid body during postnatal development

Immunocytochemical studies of the rat carotid body during postnatal development revealed neuropeptide Y (NPY), tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH) immunoreactivities. In adult rats (at postnatal week 10), NPY and DBH immunoreactivities were shown in a few small chief cells (cell number/section shown as mean +/- SD: NPY 3.4+/-2.6, DBH 3.2+/-2.3), in large ganglion cells, and in numerous varicose nerve fibers of the carotid body. TH immunoreactivity was found in almost all chief cells, in a few ganglion cells, and in numerous varicose nerve fibers in the carotid body. By using the double-immunostaining technique, most NPY-immunoreactive chief cells, ganglion cells, and nerve fibers exhibited DBH immunoreactivity. The NPY- and DBH-immunoreactive chief cells in the rat carotid body were numerous from birth (NPY 93.8+/-14.9, DBH 89.7+/-12.3) to postnatal week 1 (NPY 65+/-14.5, DBH 61.6+/-11.3), but decreased quickly from postnatal week 2 (NPY 6.1+/-3.5, DBH 3.6+/-2.8) onwards. A few NPY- and DBH-immunoreactive ganglion cells were found in the periphery or in the center of the rat carotid body during postnatal development. TH immunoreactivity was observed in almost all chief cells and in a few ganglion cells in all developmental stages. NPY- and DBH-immunoreactive nerve fibers were very scarce in the carotid body from birth to postnatal week 1, began to increase gradually after postnatal week 2, and reached the adult level by postnatal week 5. The present study suggests that the expression of NPY and noradrenaline in chief cells and in the nerve fibers of the rat carotid body may be regulated during postnatal development.     

支原体培养液中抑制HIV—1 RT活性物质的分子性状

对支原体培养液进行的高效液相层析分析的结果显示：具有ＤＮａｓｅ和／或ＲＮａｓｅ活性的两个主要蛋白峰（峰１分子量为６７×１０３～１００×１０３，峰２分子量为１０×１０３～２５×１０３）显示出明显的ＲＴ抑制活性。这一结果说明支原体培养液的ＲＴ活性抑制作用来自于培养液中有ＤＮａｓｅ活性和ＲＮａｓｅ活性的部分，对抑制ＨＩＶ－１活性可能有一定相关。     

Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease

Hepatitis B virus (HBV) mutants with deletions in the preS region have not been evaluated for association with viral genotypes. In a case-control study, HBV DNA samples collected from 80 each of carriers infected with HBV genotype B or C were examined for preS deletions. PreS deletion mutants were found in a total of 37 of 160 (23%) HBV carriers. Carriers with preS deletion mutants were older (56.0 +/- 12.7 vs 49.3 +/- 16.9 years, P < 0.05), were infected more frequently with HBV genotype C (84% vs 40%, P < 0.05), and had more advanced disease, such as liver cirrhosis and hepatocellular carcinoma (54% vs 31%; P < 0.05), than did those without such mutants. In a multivariate analysis, genotype C (odds ratio [OR] = 9.3, P < 0.001) and advanced liver disease (OR = 3.1, P < 0.01) were the most significant variables in association with preS deletions. A direct repeat sequence (TCAGG) was found at the start or at the end of preS1 deletions in 6 of the 20 (30%) cases examined, and preS2 deletions in these cases were clustered over the 5'-terminal half of this region. These results indicate that the development of preS deletion mutants depends on HBV genotypes and that it may be associated with progressive liver disease.     

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

In a single hospital in Tokyo, the 87 patients infected persistently with hepatitis B virus (HBV) genotype A, the 413 with B, and the 3,389 with C were compared for virological outcome. Hepatitis B surface antigen (HBsAg) was cleared from the serum in 12% (3/26), 2% (2/112), and 3% (23/826) of patients with genotypes A, B, and C, respectively, at 5 years of follow-up (P = 0.0395). Hepatitis B e antigen (HBeAg) was cleared from serum more frequently in patients with genotype B than those with A or C (78% [32/41] vs. 58% [11/19] or 45% [251/562], P = 0.00001) at 5 years. Of the 45 individuals infected with genotype A and followed for 3 years or longer, HBeAg was more frequent (16% [3/19] vs. 73% [19/26], P = 0.0002) and levels of HBV DNA higher (median <2.6 [range: <2.6-5.6] vs. >7.6 [<2.6->7.6] log copies/ml, P = 0.001) in the 26 patients with biopsy-proven chronic hepatitis than the 19 asymptomatic carriers. Among the 26 hepatitis patients infected with HBV genotype A, decreases in HBV DNA were less frequent (20% [1/5] vs. 93% [13/14] or 86% [6/7], P = 0.0095) and increases in serum levels of hyaluronic acid > or =10 ng/ml commoner (80% [4/5] vs. 14% [2/14] or 14% [1/7], P = 0.017) in the patients who kept HBeAg than in those who seroconverted or who remained HBeAg-negative. In conclusion, patients persistently infected with HBV genotype A fare better than those with genotype B or C. However, high levels of HBV DNA continue in those in whom HBeAg persists along with fibrosis in the liver.     

Thyroid volume and serum thyroglobulin levels in patients with acromegaly: correlation with plasma insulin-like growth factor I levels

The pathogenesis of the goiter that is frequently found in patients with acromegaly is not known. Using ultrasonic scanning, we measured thyroid volume in 17 euthyroid patients with acromegaly and examined the relationships among thyroid size, plasma GH and insulin-like growth factor (IGF-I) levels, and serum thyroglobulin (TG) levels. The mean estimated thyroid volume in these 17 patients was 32.8 +/- 15.5 (+/- SD) mL, significantly larger than that in normal subjects (15.4 +/- 3.1 mL), and 64.7% of the patients had multinodular goiter, as identified by ultrasonography. Thyroid volume was positively correlated with plasma GH and IGF-I levels and heel-pad thickness, but not with the serum TSH level. In 7 patients, thyroid volume decreased in association with a decline in plasma GH and IGF-I levels after surgical treatment. The serum TG level was elevated in 7 of the 15 patients in whom it was measured, and the mean value was 51.7 +/- 62.7 (+/- SD) micrograms/L (normal, 12.6 +/- 6.4 micrograms/L). We found no correlations among the serum TG and TSH levels, plasma GH and IGF-I concentrations, and/or thyroid volume. However, serum TG decreased after surgical treatment, just as did plasma IGF-I. These observations together with the results of recent in vitro studies by others suggest that IGF-I is one of the factors involved in goiter formation, but the elevated serum TG levels in acromegaly are controlled not only by IGF-I but also by other factors.     

PIVKA-II (protein induced by vitamin K absence-II) status in newborns exposed to anticonvulsant drugs in utero

Using PIVKA-II and Hepaplastin test, 5 neonates exposed to anticonvulsant drugs in utero were assessed 5 days after birth. None showed any sign of clinical bleeding, but all had PIVKA-II values over 1 microgram/ml. In controls, only 96 of 1,166 (8.2%) neonates had PIVKA-II values over 1 microgram/ml. The difference in the incidence rate was significant (p less than 0.005). Three of 5 epileptic mothers received valproatic acid and/or diazepam but no barbiturates and/or hydantoin.     

Exercise-Induced Ventricular Arrhythmia after Repair of Tetralogy of Fallot

Treadmill exercise electrocardiography (TE) was recorded in 50 patients to evaluate the incidence of exercise-induced ventricular arrhythmias (VAs) in a group of patients who underwent corrective surgery of tetralogy of Fallot (TF) more than four years previously. The results of rhythm evaluation were correlated with cardiac catheterization data as well as clinical information such as the age at surgery and the interval from surgery. Of the 50 patients tested, ventricular premature contraction (VPC) was confirmed in 12 patients (24%) on TE, while five patients (10%) demonstrated VPC on the standard ECG. The interval from surgery was significantly longer in those patients with VA (Group 1) than those without VA (Group 11) on TE (p<0.05). There was no significant difference of the age at corrective surgery between the two groups. In group I, the preoperative hemoglobin level was higher (p<0.05) and the right ventricular ejection fraction was lower (p<0.01). Exercise-induced VAs are closely related to the length of period after surgery and the depressed right ventricular function.