Abstract. Experimental renal scarring indicates that tissue transglutaminase (tTg) may be associated with the accumulation of extracellular matrix (ECM), both indirectly via TGF-␤1 activation and directly by the formation of ⑀(␥-glutamyl) lysine dipeptide bonds within the ECM. The latter potentially accelerates deposition and confers the ECM with resistance to proteolytic digestion. Studied were 136 human renal biopsy samples from a range of chronic renal diseases (CRD) to determine changes in tTg and ⑀(␥-glutamyl) lysine crosslinking. Immunofluorescence for insoluble tTg showed a 14-fold increase in the kidneys of CRD patients (5.3 Ϯ 0.5 versus 76 Ϯ 54 mV/cm 2 ), which was shown to be active by a similar 11-fold increase in the ⑀(␥-glutamyl) lysine crosslink (1.8 Ϯ 0.2 versus 19.3 Ϯ 14.2 mV/cm 2 ). Correlations were obtained with renal function for tTg and crosslink. In situ hybridization for tTg mRNA showed that tubular epithelial cells were the major source of tTg; however, both mesangial and interstitial cells also contributed to elevated levels in CRD. This mRNA pattern was consistent with immunohistochemistry for soluble tTg. Changes in renal tTg and its product, the ⑀(␥-glutamyl) lysine crosslink, occur in progressive renal scarring in humans independently of the original etiology and in a similar manner to experimental models. tTg may therefore play a role in the pathogenesis of renal scarring and fibrosis in patients with CRD and can therefore be considered a potential therapeutic target.

MCs as an infiltrating hematopoietic cell and its growth factor (SCF) seem to be up-regulated in glomerulonephritis, and may play a role in the development of renal fibrosis.

Long-term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so-called MIA syndrome. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C-reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM-1 was estimated using enzyme-linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (<6.0 mg/L). A statistically significant correlation was found between endotoxin and CRP levels (r = 0.47, P = 0.001). The mean pre-HD level of VCAM was 1851.00 ng/mL, while the mean post-HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post-HD rise in sVCAM-1.

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Although SN may start as glomerulopathy associated with increased mesangial cellularity, the interstitial rather than the glomerular markers of myofibroblastic differentiation and those of cell turnover are playing a crucial role in late stages of schistosomal, but not in non-schistosomal nephropathies.

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including 15 graduate students) and 53 nonmembers (including 16 graduate students). There were 17 invited speakers, with three from the USA, five from the EU and five from the UK.Jean Schwarzbauer (Princeton University, USA) opened the meeting by describing her recent findings concerning the events that control fibronectin (Fn) matrix assembly. The assembly of Fn matrix fibrils is influenced by extracellular factors such as availability of Fn and other matrix molecules, and intracellular signalling pathways mediated by integrin receptors. Jean's group has investigated two kinases downstream of integrin receptors, focal adhesion kinase (FAK) and pp60-Src. Mouse fibroblasts lacking FAK were found to assemble reduced amounts of Fn fibrils. Src family kinases phosphorylate FAK, and it was found that fibroblasts without Src family kinases (SYF cells) or wild-type cells treated with an Src inhibitor (PP1) also lack Fn matrix. The extracellular influence of tenascin-C was also discussed. In fibroblasts on a 3D Fn matrix, FAK was constitutively phosphorylated, whereas in the presence of tenascin-C, FAK is transiently activated, and there is a reduction in the assembly of Fn matrix fibrils. Other aspects of integrin-Fn interactions were also described, including the stimulation of Fn matrix formation by dexamethasone in the tumourgenic cell line HT1080.Karl Kadler (University of Manchester) summarized findings on the molecular and cellular basis of collagen fibrillogenesis. The talk focussed on the sorting and secretion of type-I collagen in organ cultures of embryonic chick tendon. It Int.