In vitro effects of interleukins on human mesangial cells: Implications for glomerulonephritis

Intrinsic glomerular cells, especially mesangial cells, are considered to be actively involved in the pathogenesis of glomerulonephritis (GN), but the precise mechanism(s) remains elusive. We have previously demonstrated that nephritogenic IgA immune complex can stimulate human mesangial cells (HMCs) to increase their production of interleukin-1 (IL-1) and interleukin-6 (IL-6). In order to evaluate the roles of cytokines such as IL-1 and/or IL-6 and mesangial cells as mediators of renal injury in GN, we have now examined the changes of HMCs and their secreted products in vitro, after stimulation with various concentrations of IL-1 and IL-6. Cytokine-activated HMCs showed the following changes: (1) increased cell size, with intracytoplasmic vaculoes, dilated endoplasmic reticulum, increased free ribosomes and polysomes, and mitochondrial swelling; (2) increased cell proliferation, reflected in thymidine incorporation and an increased proportion of S and G2/M phase cells by cell cycle analysis; (3) enhancement of IL-6 mRNA expression in HMCs with stimulation of IL-6 alone or IL-1 plus IL-6; and (4) release of large amounts of platelet activating factor (PAF), thromboxane B2 (TxB2), and superoxide anion. Taken together, these results strongly suggest that mesangial cell proliferation and increased production of immune/chemical mediators and superoxide anion can be directly induced by IL-1 plus IL-6. These changes may lead to ongoing renal injury.     

Immune Abnormalities Induced by Human Endogenous Retroviral Peptides: With Reference to the Pathogenesis of Systemic Lupus Erythematosus

P15E is a specific sequence among the envelope gene (env)-encoded transmembrane proteins of exogenous and endogenous retroviruses. A synthetic peptide (CKS-17) that shows homology to this p15E region in several species of retrovirus is known to induce immune abnormalities. In this study, we examined the effect of a synthetic peptide derived from a region of human endogenous retrovirus (HERV) clone 4-1 ( 4-1) similar to sequences of CKS-17 on the induction of systemic lupus erythematosus (SLE)-related immune abnormalities. Our results indicated that this peptide could induce T-cell activation and anergy in normal peripheral blood mononuclear cells, and the peptide could also promote the production of interleukins IL-6 and IL-16. These phenomena are representative immune abnormalities observed in SLE patients. Thus, our findings support the possibility that HERV acts as a pathogen in human SLE.     

Induction of Ly-6A/E expression by murine lymphocytes after in vivo immunization is strictly dependent upon the action of IFN-alpha/beta and/or IFN-gamma

Ly-6A/E is a phosphatidylinositol-linked membrane protein which mediates murine T and B cell signalling. IFN-gamma, IFB-alpha/beta, LPS, and IL-4 have all been reported to induce or upregulate Ly-6A/E by normal lymphocytes. Since no systematic study has addressed the stimulant selectivity of Ly-6A/E expression by murine lymphocytes nor investigated its induction and regulation during primary in vivo immune responses we analyzed in vitro Ly-6A/E expression after murine stimuli and during a number of distinct in vivo immunizations. We show that LPS induces B cell Ly-6A/E in vitro by stimulating the release of IFN-alpha/beta by 'contaminating' adherent cells. In the presence of anti-IFN-gamma + anti-IFN-alpha/beta antibodies, no Ly-6A/E was induced upon addition of multiple cytokines, including IL-4, or mitogenic doses of anti-Ig antibody. Furthermore, IFN-gamma-containing, CD4+ T cell (Th1) supernatants potently induced Ly-6A/E by murine B cells whereas IL-4-containing (Th2) supernatants were either weak or ineffective; anti-IFN-gamma + anti-IFN-alpha/beta inhibited Ly-6A/E induction by both Th1 and Th2 supernatants. Immunization of mice with Brucella abortus or poly (I).poly (C) resulted in induction of Ly-6A/E expression by virtually all B and T cells, whereas injection of G alpha M delta led to peak induction of Ly-6A/E by approximately 50% of both B and T cells. Lymphocytes from mice infected with the nematode parasites Nippostrongylus brasiliensis or Heligmosomoides polygyrus expressed no Ly-6A/E.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatitis C virus seroprevalence in Italian haemophiliacs injected with virus-inactivated concentrates: five year follow-up and correlation with antibodies to other viruses.

The overall prevalence of anti-HCV antibody in a group of 125 haemophiliacs was 62%. Four patients who had never received replacement therapy were anti-HCV negative. Of the 121 patients injected regularly with commercial concentrates, 76 were already anti-HCV seropositive in 1985 and remained so throughout the follow-up. Two patients seroconverted in 1987 without obvious signs or symptoms of hepatitis. Our patients were treated with dry heat-treated concentrates since 1985 and with wet heat- or solvent/detergent-treated concentrates since 1988. The absence of further seroconversions and of symptoms of acute post-transfusion non-A, non-B hepatitis since 1988 suggest that present virucidal treatments of concentrates are effective in preventing HCV transmission. Anti-HCV positivity appeared to be unrelated to the type and degree of haemophilia as well as to the presence of antibodies to hepatitis B virus, human immunodeficiency virus type 1, and human herpesvirus type 6.     

Multiple sulphatase deficiency presenting at birth

A new case of multiple sulphatase deficiency with onset at birth is described. The patient had many dysmorphic features and hydrocephalus, similar to one other case with early onset described in the literature. The new patient differed from the other case in having chondrocalcificans congenita, heart abnormalities and an abnormal fold of tissue present between the laryngeal inlet and the oesophagus. Excessive mucopolysacchariduria was present and there was profound deficiency of all sulphatases examined in plasma, leucocytes and cultured skin fibroblasts.     

Light and ultrastructural features of lymphoepithelial lesions of the salivary glands in Mikulicz's disease

This investigation deals with the histogenesis of the so-called 'epimyoepithelial islands' in Mikulicz's disease of the major salivary glands and is based on light and electron microscopic study in six patients. The 'epimyoepithelial islands' represent collapsed acini prior to their complete involution and disappearance, the intraductal cellular proliferation, stratification and differentiation into luminal and peripheral myoepithelial cells with partial and complete obliteration of their lumina and finally, cord-like proliferation and formation of nests of residual pluripotential cells showing squamous metaplasia and occasional myoepithelial cell differentiation. A pink, homogeneous and hyaline material on light microscopic examination is multilayered and extracellular and is in close association with the basal lamina when viewed with electron microscope.     

Cytokine profile in systemic lupus erythematosus,rheumatoid arthritis,and other rheumatic diseases

We investigated serum levels of interleukin-6 (IL-6), interferon-gamma (IFN-), and tumor necrosis factor alpha (TNF) from patients with systemic lupus erythematosus (SLE) and its various clinical manifestations of disease and from patients with rheumatoid arthritis (RA) and other rheumatic diseases. The serum levels of IL-6 and IFN- were highly elevated from patients with SLE associated with lymphadenopathy (LN) or nephrotic syndrome (NS). On the contrary, the serum levels of TNF were elevated from most patients with SLE associated with thrombocytopenia (TP). However, serum levels of TNF were in the normal range from patients with SLE associated with NS, LN, or central nervous system disease. Of interest, patients with SLE associated with humoral immunodeficiency disorder, hypogammaglobulinemia, had highly elevated levels of serum IL-6. The concanavalin A-stimulated mononuclear cells (MNC) of patients with SLE associated with TP secreted highly elevated levels of TNF compared to other patient groups. We suggest that abnormal production of various cytokines in SLE is an intrinsic defect of MNC and the immune system that may be the key element for a variety of clinical manifestations of this disease.     

Trisomy 6qter

A previously reported patient with trisomy for the distal part of 6q was shown by R-banding to be trisomic for 6q26qter, due to a t(6;22)(q26;p12) mat. Altogether nine patients with 6qter trisomy have been reported. The main features of the 6qter trisomy syndrome are: severe mental and growth retardation; acrocephaly and brachycephaly; a carp-shaped mouth; micrognathia; a very short neck with unusual anterior webbing; joint contractures; the absence of severe inner organ malformations; and survival into adulthood.     

A patient with an interstitial deletion of the short arm of chromosome 6

The clinical history and subsequent progress of a child with an interstitial deletion in the short arm of chromosome 6 is described. This abnormality coupled with a reduced Hageman factor (Factor XII) led to an earlier publication which suggested that this gene was localized to the breakpoint region involved. A review of similar phenotypes from the literature is presented.