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.     

Variable regions of antibodies to synthetic polypeptides--I. Characterization of an idiotope expressed on antibodies and T-cell factors

Spleen cells from a Lewis rat immunized with affinity-purified B10 anti-(T,G)-A-L antibody were fused with the non-secreting murine hybridoma SP2/0. Cell lines secreting monoclonal antibodies specific for mu- and kappa-chains, as well as an idiotope on anti-(T,G)-A-L antibodies, were isolated and characterized. The anti-mu and -kappa antibodies, are true anti-isotypes, reacting with sera from all strains of mice tested. The anti-idiotope antibodies recognize a determinant on antibodies binding a GT-containing epitope. The proportion of anti-GAT antibody bearing the idiotope varies markedly in different murine strains. A 1000-fold higher level of antibody from Igha mice than from Ighb and Ighe mice is required to give an equivalent inhibition of the idiotope-anti-idiotope reaction. Analysis of monoclonal antibodies expressing the idiotope indicates that the affinity of binding between idiotope and anti-idiotope can vary by as much as two orders of magnitude. Immunoadsorbants prepared with anti-idiotope antibody bind suppressor factor secreted by a GAT-specific T-cell hybridoma.     

Inflammatory cytokine levels in paw tissues during development of rat collagen-induced arthritis: Effect of FK506, an inhibitor of T cell activation

Objective and design: To characterize rat collagen-induced arthritis (CIA) on the basis of levels of inflammatory cytokines, tumor necrosis factor (TNF)-, interleukin (IL)-1 and IL-6 in paw tissues, and further investigate the effect of FK506 (tacrolimus), a potent inhibitor of T cell activation, on cytokine levels.Methods: CIA was induced in female Lewis rats. The volume of hindpaws was measured before and after collagen immunization. TNF-, IL-1 and IL-6 levels in paw tissue extracts were determined by ELISA. Proteoglycan contents of cartilage in femoral heads was measured as an indication of cartilage destruction. To assess the effect of FK506 on inflammatory cytokine levels, rats were orally treated with 5 mg/kg of FK506 from days 14–21.Results: TNF- a level in paw tissues did not significantly change compared to levels found before collagen immunization, throughout development of CIA. In contrast, IL-1 and IL-6 levels in paw tissues significantly increased between day 14 and day 28 after collagen imuninization, when the arthritis was at a developed stage. Therapeutic treatment with FK506 reduced the elevated level of IL-6, but not IL-1, in paw tissue. FK506 treatment was effective in suppressing paw swelling and also recovering the loss of proteoglycan contents in the cartilage.Conclusions: Levels of IL-1 and IL-6, but not TNF- , in paw tissue were upregulated in association with the development of arthritis in rat CIA. These results suggest that IL-1 and IL-6, rather than TNF- , may play important roles at local inflammatory sites in producing joint destruction in rat CIA. FK506 may improve arthritis in established stages of CIA, by reducing the elevated level of IL-6.Received 4 March 2004; returned for revision 2 April 2004; accepted by M. J. Parnham 9 April 2004     

IL-4 induces IL-6 and signs of allergic-type inflammation in the nasal airways of nonallergic individuals

In addition to its more widely recognized role in promoting IgE synthesis, we speculate that interleukin-4 (IL-4) may modulate both allergic- and nonallergic-type inflammatory processes in the airway mucosa. We examined in vivo the effect of IL-4 on granulocyte and cytokine homeostasis in the nasal airways of nonallergic volunteers. Ten (N = 10) healthy subjects received nasal IL-4 (10 microg) or saline (0.9%) challenges on separate occasions. Nasal lavage was obtained before and 24 h after nasal challenges. We report that IL-4 induced a significant increase in IL-6 and produced elevated levels of eosinophils and neutrophils compared to saline. These data demonstrate that IL-4 can modulate both allergic- and nonallergic-type inflammatory responses in the nasal airways of nonallergic individuals.