HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation.

HIV-infected patients suffer several renal syndromes, which can progress rapidly from renal insufficiency to end-stage renal disease. Histologically, HIV-induced nephropathy is characterized by prominent tubulopathy with apoptosis of tubular cells. Clinical and experimental evidence suggests that renal injury may be directly related to virus infection. Although HIV-1 is a polytropic and not solely lymphotropic pathogen, the susceptibility of renal cells to HIV-1 remains to be determined. This paper demonstrates in vitro the permissiveness of proximal tubular epithelial cells (PTEC) to HIV-1 and describes the effects of PTEC infection to explain the pathogenesis of tubular damage in vivo. The results indicate that PTEC express HIV-specific receptor and coreceptors and sustain virus replication. We observed that HIV-1 infection causes the death of tubular cells by triggering an apoptotic pathway involving caspase activation. Fas upregulation but not Fas ligand expression was found in the infected PTEC. However, after HIV-1 infection, tubular cells became susceptible to apoptosis induced through Fas stimulation. Caspase inhibition prevented the death of the infected PTEC in spite of persistent viral replication. These findings may explain the prominent histopathology of HIV-associated nephropathy and demonstrate that the apoptosis of nonlymphoid cells can be directly induced by HIV-1.

[Roberts' syndrome. Review of the literature and presentation of 2 clinical cases]. / Sindrome di Roberts. Revisione della letteratura e presentazione di due casi clinici.

Two new cases of Robert's Syndrome (R.S.) are presented. Both clinic and cytogenetic aspects of R.S. are rapidly reviewed. The significance of cytogenetic findings in R.S. is discussed.

Primary and immortalised human pancreatic islet endothelial cells: phenotypic and immunological characterisation.

AIMS/HYPOTHESIS: Studies on the biology of the microvascular endothelial cells (MECs) that surround and penetrate the pancreatic islets are hampered by difficulties in isolating and culturing large numbers of pure cells. We aimed to morphologically and functionally characterise primary MECs purified and cultured from human islets, and to establish a simian virus 40 (SV40)-immortalised cell line from these primary cultures. MATERIALS AND METHODS: Human islet MECs were extracted and purified using anti-CD105 coated immunomagnetic beads, and endothelial markers and surface molecules analysed by flow cytometric analysis. An immortalised cell line was then established by using a chimeric adeno5/SV40 virus. RESULTS: Islet MECs expressed classic and specific endothelial markers, a high basal level of intercellular adhesion molecule-1, and low levels of E-selectin and TNF (previously known as TNF-alpha) inducible vascular cell adhesion molecule-1. IFNG (previously known as IFN-gamma) induced expression of HLA class II molecules. The immortalised islet MECs expanded rapidly, exhibited increased DNA synthesis, and were passaged approximately 30 times, without signs of senescence. They retained the endothelial characteristics of the parental cells, and behaved as the primary cells in terms of TNF stimulation of expression of adhesion molecules and support of leucocyte adhesion and transmigration. CONCLUSIONS/INTERPRETATION: The immortalised islet MECs that we have established could effectively represent a substitute for primary counterparts for in vitro studies on the role of the microvasculature in pathophysiological processes involved in type 1 and type 2 diabetes.

Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells.

The six group B coxsackieviruses (CVBs) are highly prevalent human pathogens that cause viremia followed by involvement of different organs. Clinical and experimental evidence suggests that CVBs can induce kidney injury, but the susceptibility of human renal cells to these viruses is unknown. By using pure cultures of human glomerular and tubular cells, we demonstrated that all CVBs are capable of productively infecting renal cells of three different histotypes. Distinct pathogenic effects were observed. Proximal tubular epithelial cells and, to a lesser extent, glomerular podocytes were highly susceptible to CVBs; in both cases, infection led to cytolysis. In contrast, glomerular mesangial cells supported the replication of the six CVBs but failed to develop overt cytopathologic changes. Mesangial cells continued to produce infectious progeny for numerous serial subcultures (i.e., more than 50 days), especially with type 1, 3, 4, and 5 viruses. In the above cells, persistent infection induced the de novo synthesis of platelet-derived growth factor A/B and enhanced the release of transforming growth factor beta1/2. These two factors are important mediators of progression from glomerular inflammation to glomerulosclerosis. CVB replication appeared also to impair the phagocytic and contractile activity of mesangial cells. Loss of these properties--which are important in glomerular physiopathology--may contribute to the development of progressive nephropathy. The results show that CVBs induce distinct effects in different types of cultured renal cells and suggest that CVB infections may be associated with both acute and progressive renal injury.

Derangements of immunoglobulin levels, phytohemagglutinin responsiveness and T and B cell markers in Down's syndrome at different ages.

Immunologic studies were performed in 83 patients with Down's Syndrome (DS) in ages ranging from a few months to 30 years and 76 karyotypically normal age-matched controls. The results show that both thymus-dependent and independent functions were impaired in DS with a characteristic age sequence. Serum immunoglobulin levels were normal in children with DS less then 5 years old; after 6 years of age a definite hyperglobulinemia of the IgG and IgA type was observed. A slight decrease in IgM was observed between 16 and 25 years of age. In subjects with DS lymphocyte phytohemagglutinin responsiveness was in the normal range during the first decade but it decreased thereafter progressively; the percentage and absolute number of peripheral blood lymphocytes forming "spontaneous rosettes" with sheep erythrocytes were abnormally low at all ages including infancy; the number of circulating lymphocytes with a high density of surface immunoglobulins was always in the normal range.

The 11q;22q translocation: a collaborative study of 20 new cases and analysis of 110 families.

Following a previous collaborative study (Fraccaro et al. 1980), 20 new cases of 11q;22q translocation are described. Twelve families were ascertained through an unbalanced carrier of the translocation and eight cases were ascertained as balanced carriers. A segregation analysis was performed on the 110 families so far published. It was concluded that the 11q;22q translocation is a relatively frequent event, and that all the cases thus far reported might have the same breakpoints at 11q23.3 and 22q11.2. The translocation seems to be independent of environmental factors and it seems to have a low rate of mutation as indicated by the scarcity of de novo cases. The new data confirmed that only one type of unbalanced karyotype (47,XX or XY+der(22)t(11;22)(q23.3;q11.2)) is found among the offspring of the translocation carriers. The minimal overall recurrence risk for an unbalanced translocation was estimated to 2%. There was no difference between the recurrence risks for male and female balanced carriers, while the trend was confirmed of an excess of female balanced carriers among the phenotypically normal offspring of the t(11;22) female carriers.