CORRELATION BETWEEN GLYCOCONJUGATE EXPRESSION AND FUCOSYLTRANSFERASE ACTIVITY IN HUMAN COLORECTAL CARCINOMA

Using the surgically extirpated specimens from 9 patients with colorectal carcinoma, fucosyltransferase activities in the carcinoma tissue and the normal mucosa were measured and were compared with the hlstochemical findings of glycoconjugates which were shown by staining with lectins reacting with blood group antigens and related substances. The fucosyltransferase activities of the carcinoma tissue were well correlated with the overall findings of lectin stainings after neuraminidase treatment. The more intense the carcinoma tissue was stained, the higher the fucosyltransferase activity was shown. However, there were marked differences in the fucosyltransferase activities by the portions measured, depending upon the relative amount of carcinoma tissue and Interstitial tissue; in the invasive portion with less carcinoma tissue, the activity was generally low in comparison with that in the surface area where carcinoma tissue was rather abundant. Thus, the morphological and lectin hlstochemical finding are of paramount importance for the eveluation of glycosyltransferase activity in human colorectal carcinoma.     

Grading score system: A method for evaluation of the degree of senescence in Senescence Accelerated Mouse (SAM)

For evaluation of the degree of senescence in SAM-P, accelerated senescence prone mouse, formerly called SAM or prone series or P-series, consisting of SAM-P/1, SAM-P/2, SAM-P/3 and SAM-P/4 corresponding to P-1, P-2, P-3 and P-4 series, respectively, in the previous reports, and in SAM-R, accelerated senescence resistant mouse, formerly called resistant series or R-series, consisting of SAM-R/1, SAM-R/2 and SAM-R/3 corresponding to R-1, R-2 and R-3 series, respectively, in the previous reports, the grading score system was adopted. The items to be examined in this system include 11 categories selected from the clinical signs and gross lesions considered to be associated with the aging process. The degree of the senescence in each category was graded from 0 to 4 according to the detailed criteria devised in our laboratory. After 8 months of age each mouse was examined every 4 months, and some of the mice were examined after 2 months of age.In almost all categories, the grading score and incidence began to increase from 4 or 6 months of age and continued to increase with advancing age in both SAM-P and SAM-R. The increase, however, was more marked in SAM-P than in SAM-R. The slow but steady increase in the SAM-R levelled out at 24 months of age and was comparable to that of 12 months of age in SAM-P. In both SAM-P/1 at 8 months of age and SAM-R/2 at 12 months of age, there was a significant reverse correlation between total score of this grading score system and length of residual life after examination.Systematic and extensive studies using the grading score system showed that if the validity of the system is, based on “irreversibility” and “universality” of the changes in     

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.     

Two cases of a renal epithelial tumour resembling immature nephron

Summary Two cases of renal epithelial tumours are reported in females aged 46 and 66 years respectively. In spite of the large size of the tumours, neither invasive growth nor metastasis was observed. Histologically, the tumours were composed of immature epithelial cells forming tubules with abortive glomeruloid structures. Electron microscopy of tumour cells revealed poorly developed polarity and intracytoplasmic organelles. They showed similar immunohistochemical reactions to those of developing nephrons, particularly to those of the S-shaped body. The nuclear DNA content of the tumour cells was almost euploid. We conclude that the lesions were epithelial tumours of the kidney histologically mimicking developing renal parenchyma.     

Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3

The aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs.     

Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases,Axl and Sky,in human uterine endometrium and ovarian endometriosis

We demonstrated the expression of Gas6, the protein product of the growth arrest-specific gene 6 (gas6) and a member of the vitamin K-dependent protein family, and its receptor tyrosine kinases, Axl and Sky, in human uterine and ovarian endometriotic endometria using RT-PCR-Southern blot analysis and immunohistochemistry. Gas6, Axl and Sky mRNA were detected in all samples analysed. There was no significant difference between the levels of Sky mRNA in normal uterine and endometriotic endometria; however, the levels of Gas6 and Axl mRNA in endometriotic endometria were significantly higher than in normal endometria. These mRNA levels showed no significant alteration during the menstrual cycle. In the immunohistochemical study, Gas6, Axl and Sky were found in endometrial glandular cells and stromal cells in all samples analysed. This study demonstrates the coexpression of receptor tyrosine kinases and their ligand, Gas6, in normal uterine and ovarian endometriotic endometria, and the overexpression of Axl and Gas6 in endometriotic endometria. It is suggested that Gas6 and Axl signal transduction is aberrantly stimulated in endometriotic endometria, and is plausibly related to its growth potential.     

Effects of vitamin D and estrogen receptor gene polymorphisms on the changes in lumbar bone mineral density with multiple pregnancies in Japanese women

BACKGROUND: Our aims were to follow the longitudinal changes in lumbar spine bone mineral density (BMD) with multiple pregnancies, and to study whether polymorphisms in the vitamin D receptor (VDR) and estrogen receptor (ER) genes may influence the results. METHODS: We repeatedly measured the BMD of the lumbar spine (L2-L4) of 133 women who had undergone two successive pregnancies and 73 non-pregnant controls, and analysed the restriction fragment length polymorphisms using restriction endonucleases TaqI, ApaI and FokI for the VDR gene, and PvuII and XbaI for the ER gene. RESULTS: Cases and controls had no significant differences in the longitudinal BMD changes. The mean percentage change in lumbar BMD (DeltaBMD%) of the women with the XX/Xx genotype was significantly lower than that of the women with the xx genotype after adjusting for age at each delivery, BMD of the first scan, and interval between the scans (0.2 +/- 3.3 versus 2.0 +/- 4.2%; P=0.030, analysis of covariance). Multiple regression analyses to evaluate the contribution of the XbaI polymorphism of the ER gene on DeltaBMD% showed that the percentage decrease in BMD was greater for women lacking the XbaI restriction site (adjusted R2=0.188, P<0.0001). CONCLUSIONS: The present study suggests that the DeltaBMD% was significantly influenced by the XbaI polymorphism of the ER gene.     

The lectin-complement pathway – its role in innate immunity and evolution

Summary: Innate immunity was formerly thought to be a non‐specific immune response characterized by phagocytosis. However, innate immunity has considerable specificity and is capable of discriminating between pathogens and self. Recognition of pathogens is mediated by a set of pattern recognition receptors, which recognize conserved pathogen‐associated molecular patterns (PAMPs) shared by broad classes of microorganisms, thereby successfully defending invertebrates and vertebrates against infection. Lectins, carbohydrate‐binding proteins, play an important role in innate immunity by recognizing a wide range of pathogens. Mannose‐binding lectin (MBL) and ficolin are lectins composed of a lectin domain attached to collagenous region. However, they use a different lectin domain: a carbohydrate recognition domain (CRD) is responsible for MBL and a fibrinogen‐like domain for ficolin. These two collagenous lectins are pattern recognition receptors, and upon recognition of the infectious agent, they trigger the activation of the lectin‐complement pathway through attached serine proteases, MBL‐associated serine proteases (MASPs). A similar lectin‐based complement system, consisting of the lectin–protease complex and C3, is present in ascidians, our closest invertebrate relatives, and functions in an opsonic manner. We isolated several lectins homologous to MBLs and ficolins and several MASPs in invertebrates and lower vertebrates, and herein we discuss the molecular evolution of these molecules. Based on these findings, it seems likely that the complement system played a pivotal role in innate immunity before the evolution of an acquired immune system in jawed vertebrates.