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The incidence and type of infections were retrospectively analyzed in 21 infants with congenital nephrosis of the Finnish type (CNF). During the median follow-up time of 1.1 years the infants suffered from 63 verified and 62 suspected episodes of sepsis. These accounted for half of all infections recorded. Forty percent of bacteremias were caused by coagulase-negative staphylococci, 16% were caused by Staphylococcus aureus, 17% were streptococcal, and 24% were caused by Gram-negative bacteria. One infant died of pleural empyema, but otherwise the outcome of infections was good. The use of central venous lines tended to increase the rate of staphylococcal bacteremias but had no significant effect on the overall incidence of infections. Prophylactic use of antibiotics did not reduce the incidence of septic or other infections. Infants with CNF had low levels of serum IgG, but prophylactic immunoglobulin infusions (0.5-1.0 g once or twice a week) did not reduce the frequency of infections, probably because the infused IgG was quickly lost into the urine. The results indicate that infants with CNF often suffer from septic infections associated with the invasive treatment modalities. Parenteral antibiotics covering the hospital strains of bacteria (especially staphylococci) should be started without delay when a nephrotic patient is not doing well.

Binding of bacterial adhesins to rat glomerular mesangium in vivo . Two well characterized bacterial adhesins, the O75X fimbriae of Escherichia coli and the type-3 fimbriae of Klebsiellae , with in vitro affinities to type IV and V collagens, respectively, were used to test whether bacterial components with affinity for glomerular matrix could bind to glomeruli in vivo . The purified fimbrial proteins were injected into rats, and kidney samples were studied by immunofluorescence at two hours to nine months postinjection. The O75X, but not the type-3 fimbriae, formed mesangial deposits that persisted for months. Preincubation of the O75X fimbriae with type IV collagen significantly reduced the glomerular binding. The fimbrial deposits were extracellular, as anti-O75X IgG injected into rats bound to glomeruli. Proteinuria or histological damage could not be detected even after passive or active immunizations of the rats. The results demonstrate that bacterial adhesins may bind in vivo to and persist in glomeruli by their specific affinities. The results also indicate that additional factors provided by the bacteria or the host are needed for glomerular damage to take place.

We present a fatal case of Yersinia pseudotuberculosis sepsis with global cardiac dysfunction and shock, where the plasma levels of endotoxin, TNF-α and interleukin IL-1-β were undetectable, IL-6 was low and IL-10 was increased 3 h before death.

We describe here the size and location of nephrin, the first protein to be identified at the glomerular podocyte slit diaphragm. In Western blots, nephrin antibodies generated against the two terminal extracellular Ig domains of recombinant human nephrin recognized a 180-kDa protein in lysates of human glomeruli and a 150-kDa protein in transfected COS-7 cell lysates. In immunofluorescence, antibodies to this transmembrane protein revealed reactivity in the glomerular basement membrane region, whereas the podocyte cell bodies remained negative. In immunogold-stained thin sections, nephrin label was found at the slit between podocyte foot processes. The congenital nephrotic syndrome of the Finnish type (NPHS1), a disease in which the nephrin gene is mutated, is characterized by massive proteinuria alreadyin uteroand lack of slit diaphragm and foot processes. These features, together with the now demonstrated localization of nephrin to the slit diaphragm area, suggests an essential role for this protein in the normal glomerular filtration barrier. A zipper-like model for nephrin assembly in the slit diaphragm is discussed, based on the present and previous data.

Purpose: To analyze the route of aqueous humor contamination leading to thedevelopment of postoperative endophthalmitis. Setting: Department of Ophthalmology, University of Helsinki, Finland. Methods: Forty-nine eyes of 49 patients (31 having phacoemulsification and 18 extracapsularcataract extraction [ECCE]) participated in the study. Four bacterial cultures were taken: preoperative conjunctival swab, lid margin culture, intraoperative lacrimal lake sample, and immediate postoperative anterior chamber fluid sample. Results: Preoperative lid margin cultures were positive in 59.2% of eyes, conjunctival cultures in 69.4%, and lacrimal lake cultures in 24.9%. Four aqueous humor samples (8.2%) showed bacterial growth in the anterior chamber aspirate: 3 in the phacoemulsification and 1 in the ECCE group. The bacteria isolated in this study, Staphylococcus epidermidis and Propionibacterium acnes (2 positive isolates each) were sensitive to the preoperative topical antibiotics used. No aqueous humor sample or any from other locations showed gram-negative microbe growth. The most frequently recovered microbes in all samples collected from the 3 other sources were S epidermidis and other coagulase-negative staphylococcus species, followed by P acnes and other propionibacterium species, Staphylococcus aureus , and diptheroids. Conclusion: The ocular surface significantly contributed fo the transmission ofmicrobes into the eye during cataract surgery. These microbes could not be eradicated by topical preoperative antibiotics. However, no patient developed postoperative endophthalmitis. Natural defense mechanisms appear to fend off a minor inoculum with these microbes of relatively low pathogenicity.

The aim of this study was to examine the distribution of beta 1 and alpha v integrins (Ints) and some of their ligands in the kidneys of patients with congenital nephrotic syndrome of the Finnish type (CNF) and in controls using indirect immunofluorescence with monoclonal antibodies. The mesangial reactivity of Int alpha 1 and Int beta 1 subunits was more variable and an increased glomerular reactivity with Int alpha 3 and Int-alpha 6 antibodies was found in CNF kidneys than in controls. Int alpha 2 subunit was either completely missing from or found in significantly lesser amounts in CNF kidney glomeruli. The immunoreactivity for Int alpha v was more variable, fainter and also more granular in CNF samples than in control kidneys. The glomerular reactivity for Int beta 5 was more diffuse and weaker, and in sclerotic Bowman's capsules more intense in CNF kidneys than in controls. Immunoreactivity for Int beta 6 was restricted and was comparable in extent in CNF and control kidneys. Of the extracellular matrix components studied, the expression of EDAFn, EDBFn, OncFn, Ln alpha 2 chain, Ln beta 1 chain and tenascin was increased. This is also seen in several glomerular diseases with inflammation and sclerosis. Immunoreactivity for vitronectin was decreased. Several differences were found in the intensity or location of the immunostaining for the beta 1 and alpha v Ints and their ligands in CNF kidneys compared with controls, which have not been found in any other proteinuric disease. Disturbed Int expression pattern in CNF may specifically reflect the disturbance of glomerular function caused by the primary defect in this disease.

Yersinia pseudotuberculosis is a rare cause of disease in humans, the most common manifestation being mesenteric lymphadenitis accompanied by abdominal pain and fever. A septicemic form of Yersinia pseudotuberculosis infection has been reported only rarely. It is usually seen in patients with underlying disorders such as diabetes, hepatic cirrhosis or iron overload. Fifty-four cases of septicemic infection were found in the literature. The earlier published cases are reviewed, and four cases occurring in Finland during the period February to June 1992 are reported.

Decrease of the anionic charge of the glomerular basement membrane and especially the reduced amount of heparan sulphate proteoglycan in the lamina rara externa has been suggested to be the basic pathogenetic defect in congenital nephrotic syndrome. In the present study the anionic charge of glomeruli was examined in the congenital nephrotic syndrome of the Finnish type and in controls using cationic stains (polyethyleneimine, Ruthenium Red) in electron microscopy. Chondroitinase and heparinase treatments were used to characterize further the anionic elements detected. Scanning electron microscopy (SEM) was used in addition to transmission electron microscopy (TEM) to examine the tridimensional structure and secondary changes of podocytes in this syndrome. The number (mean +/- SD) of polyethyleneimine granules per 1 micron length of lamina rara externa of the glomerular basement membrane was 24.9 +/- 4.5 in control and 23.2 +/- 4.3 [corrected] in congenital nephrotic syndrome subjects. The Ruthenium Red staining pattern was closely similar in syndrome and control kidneys. The granules evident after staining with either cationic stain were seen after chondroitinase but not after heparinase treatment in control as well as in syndrome patient kidney samples. No denuded areas of basement membrane in 42 glomeruli from four syndrome patients were found in SEM. In conclusion, the amount of anionic sites in the lamina rara externa as detected by either cationic stain was comparable to controls. These results do not support the hypothesis of decreased anionic sites in the lamina rara externa of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type.

The heparan sulphate proteoglycan (HSPG) of the glomerular basement membrane (GBM) is considered to be mainly responsible for the charge selectivity of the GBM; decreased HSPG results in a decreased anionic charge of the GBM with increased heparan sulphate (HS) in the urine and is believed to be responsible for the proteinuria of the congenital nephrotic syndromes (CNS). Urinary HS and chondroitin sulphate (CS) concentrations in children with CNS of the Finnish type (CNF) and the total glycosaminoglycans (GAG) in amniotic fluid of CNF pregnancies were measured by three methods: Alcian blue, Safranine O and uronic acid assays. The total urinary GAG in CNF and other nephrotic patients was comparable to controls with all three methods. Urinary CS and HS in CNF did not differ significantly from controls. Total amniotic fluid GAG was also similar in CNF and control pregnancies. These results suggest some pathogenetic mechanism other than loss of glomerular HS chains in urine for the proteinuria of CNF.

Congenital nephrosis of the Finnish type (CNF) is a hereditary renal disease of unknown aetiology manifested by massive proteinuria of the newborn and unresponsive to any treatment. In this study kidney samples and cultured glomerular mesangial cells from five patients with CNF were studied by indirect immunofluorescence microscopy for the presence and location of major basement membrane matrix (GBM) components. Histological changes of glomeruli ranging from mild thickening of basement membranes to total obliteration and sclerosis were seen. Notably, thickening of the subepithelial layer of Bowman's capsules was regularly seen along with hypercellularity at the juxtaglomerular areas. The matrix components studied (laminin, plasma- and cellular fibronectin, type IV collagen, including the NC-1, alpha-1 and alpha-3 chains, heparan sulphate proteoglycan (HSPG) core protein, thrombospondin) were characteristically seen within the glomeruli. Local thickenings alternating with total loss of epitopes along the GBM were seen, especially with anti-type IV collagen and anti-HSPG antibodies. Sera from CNF patients after transplantation failed to show antibodies against GBM structures in immunofluorescence microscopy, suggesting that no missing epitopes of GBM are introduced with the transplant kidney. Cultured mesangial cells of CNF glomeruli also showed continued in vitro production of the matrix components and their incorporation into the matrix underneath the cell layer.