Changes in the expression of syndecan-1 in the colorectal adenoma–carcinoma sequence

 Syndecan-1, a transmembrane heparan sulphate proteoglycan (HSPG), functions as a matrix receptor on the basal surface of epithelial cells. It also co-localizes with E-cadherin at the lateral cell surface where its function is uncertain. Tumour development in the large bowel is associated with loss of normal epithelial adhesion and altered patterns of expression of cell adhesion molecules, possibly including syndecan-1. To evaluate changes in syndecan-1 expression during the development of colorectal neoplasia, 59 adenomas and 20 carcinomas arising from adenomas were investigated by immunohistochemistry. The staining intensity and distribution of syndecan-1 and E-cadherin in sequential sections was examined, semi-quantified and compared. Staining of syndecan-1 and E-cadherin was uniform in normal colorectal epithelial cells, and located at the basolateral surface. No significant change was seen in either molecule in mildly or moderately dysplastic adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in severely dysplastic epithelium as compared to moderate dysplasia (P=0.001 and P=0.004 respectively). Similarly, there was a significant reduction of both molecules in carcinomas compared with associated adenomas (syndecan-1 P=0.00003; E-cadherin P=0.002). In both cases the loss of syndecan-1 expression was more striking than that of E-cadherin. Previous in vitro studies have shown that epithelial cells made deficient in syndecan-1 cease to express E-cadherin, suggesting a causal association. Our results support these findings and indicate that disruption of cell-matrix adhesion is critical in colorectal carcinogenesis, probably preceding changes in the purely homotypic cell-cell adhesion mediated by E-cadherin. Received: 11 May 1998 / Accepted: 14 September 1998     

Alterations in presenilin 1 processing by amyloid-β peptide in the rat retina

Accumulating evidence indicates that mutations in the presenilin 1 (PS1) gene are responsible for most cases of familial Alzheimer’s disease (AD). Although its biological functions are not yet fully understood, it appears that PS1 plays a role in the processing and trafficking of the amyloid precursor protein (APP). However, little is known about factors that are involved in regulating the metabolism of PS1 especially in relation to AD pathology. In this study, we have examined the effect of optic nerve crush, intravitreal injection of the inflammatory agent lipopolysaccharide (LPS) or injection of amyloid β_1-42 (Aβ_1-42) on the expression and processing of PS1 in the rat retina. We found that 48 h after injection of Aβ_1-42 there was a dramatic alteration in the banding pattern of PS1 on Western blots, as indicated by marked changes in the levels of expression of some of its C- and N-terminal fragments in retinal homogenates. These results suggest an Aβ_1-42-induced potentiation of a non-specific stress-related but inflammation-independent alteration of processing of PS1 in this in vivo model.     

BamH1 polymorphism in the Chinese,Malays, and Indians in Singapore and its application in the prenatal diagnosis of β-thalassemia

Summary The distribution of restriction fragment length polymorphism (RFLP) at theBamH1 site of the -globin gene was investigated in the Chinese, Indian, and Malay race in Singapore. The sample comprised of 183 normal individuals and 35 -thalassemia carriers in which 13 were couples with at least one -major child. The results from this study indicate thatBamH1 polymorphism will be informative in 22% of pregnancies at risk for -thalassemia major in Chinese, 19% in Malays and 7% in Indians. In prenatal diagnosis usingBamH1 polymorphism for one -major affected family, the fetus was diagnosed to be normal or -carrier. The validity ofBamH1 polymorphism in the exclusion of -thalassemia major was subsequently confirmed at birth by globin chain biosynthesis.     

HLA-DRB1 and -DQB1 alleles in the Brazilian population of the northeastern region of the state of São Paulo

The HLA-DRB1 and -DQB1 alleles in 161 healthy unrelated individuals, including Caucasians, Blacks and Mulattos (mixed Caucasian and Black), from the Northeastern region of the state of S?o Paulo, Brazil were analysed. The 36 different DRB1 alleles detected included not only common Caucasian alleles, but also DRB1*0411, 0807 and 1402, typical of Amerindians, and DRB1*0302, 1503, and 0804, typical of African American Blacks.     

Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown aetiology. Interleukin (IL)-1β plays an important role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL-1β and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels. In 77 IPF patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B genes were determined. Serum and BALF IL-1Ra and IL-1β levels were measured using a multiplex suspension bead array system and were correlated with genotypes. Both in serum and BALF a significantly decreased IL-1Ra/IL-1β ratio was found in IPF patients compared to healthy controls. In the IL1RN gene, one SNP was associated with both the susceptibility to IPF and reduced IL-1Ra/IL-1β ratios in BALF. Our results show that genetic variability in the IL1RN gene may play a role in the pathogenesis of IPF and that this role may be more important than thought until recently. The imbalance between IL-1Ra and IL-1β might contribute to a proinflammatory and pro-fibrotic environment in their lungs.     

How robust is the evidence for viruses in the induction of type 1 diabetes?

Viruses associated with type 1 diabetes have eluded definition as causal, with the exception of rubella virus. False-negative results may have occurred due to the focus on subjects at symptomatic onset, who may be heterogeneous and differently affected by viruses. In addition, assays have not always been sufficiently sensitive to deal with transient infections, and pancreatic tissue is scarce. Longitudinal studies of at-risk subjects and more sensitive DNA techniques now reveal that at initiation of islet autoimmunity, enteroviruses have only a small role, but are more likely to be important at symptomatic onset. Rotaviruses remain associated with initiation of islet autoimmunity, and generate strong T cell responses in the young.     

Does the meniscus exist in the elbow joint in children?

The authors report a case of meniscus at the elbow joint in a 15-month-old infant causing a limitation of elbow extension. Histological examination demonstrated that this tissue was not a synovial fold or a chondroid metaplasia of the synovial fold. As a meniscus does not appear at any stage of the embryological evolution of the elbow joint, it has been concluded that the presence of the meniscus can be considered as an abnormal condition.     

Polymorphisms in the Genes Encoding TGF-��1, TNF-��, and IL-6 Show Association with Type 1 Diabetes Mellitus in the Slovak Population

Numerous cytokines have been shown to participate in the pathogenesis of type 1 diabetes (T1D). As gene polymorphisms can influence cytokine production or function, they may potentially contribute to genetic predisposition to the disease. The aim of this study was therefore to investigate the role of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine and cytokine receptor genes in genetic susceptibility to T1D. Polymerase chain reaction with sequence-specific primers was used to genotype cytokine SNPs and HLA-DRB1 alleles in 151 diabetics and 140 healthy individuals of Slovak origin. Univariate analysis showed that transforming growth factor (TGF)-β1 codon 10 TT homozygotes were significantly more susceptible to developing T1D than C allele carriers (P _c = 0.0066, OR = 2.46). Furthermore, tumor necrosis factor (TNF)-α −308 A allele carriers were also significantly overrepresented among the diabetics (P _c = 0.0031, OR = 2.62); however, the association of the −308 A allele with T1D might be due to its strong linkage disequilibrium with the susceptibility allele HLA-DRB1*0301. An association was also found with interleukin (IL)-6 −174 G/C and nt565 G/A SNPs; however, its significance was lost when statistical correction was applied. These data suggest that the TGF-β1 codon 10 SNP is among numerous genetic variations with small individual effects on T1D development. Moreover, a possible role of TNF-α and IL-6 SNPs cannot be ruled out, although their association with T1D was due to strong LD with the HLA class II susceptibility allele or did not withstand statistical correction, respectively.     

Regional characteristics of electrical responses (in the band 1–225 Hz) in the cerebral cortex to conditioned stimuli in operant conditioning

Power spectra of short-term (less than 1 sec) electrical responses to conditioned stimuli were studied over the frequency range 1–225 Hz in dogs during food-related operant conditioning. These spectra demonstrated regional characteristics in terms of energy levels and frequency composition. Responses were more marked in the visual and parietal areas of the left hemisphere. Power in responses to a differential stimulus were significantly lower than with responses to positive stimuli, mainly because of the high-frequency range (80–225 Hz); energy levels in these two situations were similar during prestimulus intervals. The frequency composition of responses was defined by a series of discrete frequencies in the gamma (30–80 Hz) and high-frequency ranges. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 5, pp. 658–670, September–October, 2005.     

Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves’ disease and Hashimoto’s thyroiditis in the Japanese population

The effects of amino acid variants encoded by human leukocyte antigen (HLA) class II on the development of Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) have not been fully elucidated. We investigated the HLA-DRB1 genes of 243 GD patients and 82 HT patients in the Japanese population and compared the frequencies of HLA-DRB1 alleles and HLA-DRB1 amino acid variants between these patients and the Japanese populations previously reported by another institution. The frequencies of HLA-DRB1*04:05 and -DRB1*14:03 alleles were significantly higher and those of HLA-DRB1*01:01 and -DRB1*15:02 alleles were lower in GD patients than in controls. The frequencies of HLA-DRB1*08:03 and -DRB1*09:01 alleles were significantly higher and that of the HLA-DRB1*13:02 allele was lower in HT patients than in controls. A blind association analysis with all amino acid positions identified DRß9 and DRß31 for GD and DRß9, DRß13, and DRß21 for HT. The frequency of Glu-9 was significantly higher and that of Cys-9 was lower in GD patients than in controls. The frequencies of Lys-9 and Phe-13 were significantly higher in HT patients than in controls. DRß9 and DRß13 could be critical amino acid positions in the development of GD and HT.     

Could HLA-DRB1 be the protective locus in rheumatoid arthritis?

Extensive studies in different ethnic groups have associated the susceptibility to development of rheumatoid arthritis (RA) with the third hypervariable region of the major histocompatibility complex (MHC) HLA-DRβl molecule. On the basis of recent findings in the experimental mouse model of collagen-induced arthritis. Eric Zanelli, Miguel Gonzalez-Gay and Chella David propose that the HLA-DRB1 locus is associated with protection to RA and that the actual arthritogenic peptide-presenting molecule is HLA-DQ. Thus, the development of RA would depend upon the expression of the susceptible DQ allele and the nonprotective DRB1 alleles, along with environmental factors that trigger the autoimmune process.     

α1-adrenergic receptors in the liver parenchyma in children: Changes associated with cirrhosis

All-Russian Research Center for Molecular Diagnosis and Treatment, Ministry of Health of Russia. Research Institute of Pediatrics, Russian Academy of Medical Sciences, Moscow. (Presented by Academician of the Russian Academy of Medical Sciences M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 8, pp. 134–135, August, 1992     

Effect of IL-1β Receptor Antagonist on Lipid Peroxidation in the Liver in Stress

The content of molecular LPO products increased in the liver of rats exposed to daily 1-h immobilization. IL-1β receptor antagonist limited the stress-induced intensifi cation of LPO.     

Correlation of the antiseptic resistance in Acinetobacter baumannii and the antiseptic resistance gene qacE Δ 1 located in class Ⅰ integron

In the past decade, uses of antiseptics and disinfectants in hospitals and other health care centers are rather common, but the chance to develop resistance to antiseptics and disinfectants is also increased. Acinetobacter baumannii is one of the opportunistic bacteria involving in the nosocomial infection . In the present study, the correlation of the antiseptic resistance in A . baumannii and the antiseptic resistance gene qacEΔ1 was investigated by means of determination of MICs. Meanwhile, the MICs of glutaraldehyde, chlorhexidine, benzalkonium bromide, iodophor and trichloroisocyanurate to 80 clinical isolates of A. baumannii were detected by tube dilution assay and the resistance genes intI1 and qacEΔ1 in these isolates were amplified by PCR and verified by DNA sequencer. It was found that the MIC50 for these 5 antiseptics tested were 32, 8, 8, 4 and 1μg/ml respectively, and the detection rates of intI1 and qacEΔ1 gene were 60.0% and 77.6% respectively. In addition, 55% of the 80 isolates simultaneously possessed both intll and qacEΔ1 gene, and the percentage of antiseptic resistance of A . baumannii carring both genes to benzalkonium bromide were higher than that without these two genes, however, there was no significant difference between intll and qacEΔ1 gene. The result in bactericidal efficiency assay indicated that chlorhexidine could still produce rapid and strong bactericidal effect at concentration of 1 MIC after 10 min exposure. These results suggest that the antiseptic resistance of A . baumannii to various antiseptics is correlated with the presence of the antiseptic resistance genes qacEΔ1 in bacteria, thus warning that the increase of the antiseptic resistance should not be ignored and the relative high concentration or prolonged application time is required to achieve a sufficient bactericidal effect.     

Do the mutations of C1GALT1C1 gene play important roles in the genetic susceptibility to Chinese IgA nephropathy?

Background  

The deficiency of β1,3 galactose in hinge region of IgA1 molecule played a pivotal role in pathogenesis of IgA nephropathy (IgAN). Cosmc, encoded by C1GALT1C1 gene, was indispensable to β1,3 galactosylation of IgA1. We designed a serial study to investigate the relationship between the mutations of C1GALT1C1 gene and the genetic susceptibility to IgAN.     

Studies of Selective Attention in Dogs Using the Energy Characteristics of Neocortical Potentials in the Frequency Range 1–220 Hz

Experiments were performed in dogs to study the state of selective attention formed during operant food-related training and apparent during interstimulus intervals as a state of tense expectation of the conditioned signal. Electrical activity in various parts of the neocortex, in both hemispheres, was analyzed in the frequency range 1–220 Hz (epidural electrodes) using Fourier transforms. The electrical activity of the motor area of the right hemisphere showed a predominance of high-frequency (40–200 Hz) components, as did the visual and parietal areas of the left hemisphere. The state of selective attention was associated with a different functional mosaic in the organization of neocortical electrical activity.