Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions.

Chlamydia pneumoniae (CP) has been reported to be a pathogenic agent in the mechanism leading to atherosclerosis. The majority of available data is focused mainly on coronary artery disease whereas the distribution of CP in different areas, associated with atherosclerotic disorders, has not been completely clarified. In this study we investigated the presence of CP in atheromasic plaques from five different vascular areas (basilary artery, coronary artery, thoracic aorta, abdominal aorta, renal arteries) using nested polymerase chain reaction (PCR) and immunohistochemical staining (IHC), in order to establish the putative association of CP with atherosclerotic disease. The same atheromasic plaques were also tested for the presence of Helicobacter pylori (HP) and cytomegalovirus (CMV), other putative agents of atherosclerosis, using a nested PCR technique. Our data indicate that the presence of CP can be demonstrated in 100% of patients tested, considering globally the five areas of analysis. On the other hand the presence of HP has been demonstrated in four out of 18 patients (22.2%), and CMV only in three out of 18 (16.6%). Our results strongly suggest an association between CP and atherosclerosis and highlight the need for the detection of CP in multiple vascular areas of the same patient.

Extracellular matrix of small round cell tumors of childhood: an immunohistochemical study of 67 cases.

Sixty-seven childhood tumors were studied immunohistochemically for the extracellular matrix element type IV collagen, laminin, and fibronectin. Tumors included Ewing's sarcoma, primitive neuroectodermal tumor, small cell osteosarcoma, neuroblastoma or ganglioneuroblastoma, rhabdomyosarcoma, and lymphoma. It was found that small cell osteosarcoma was often positive for fibronectin but not type IV collagen or laminin, a new observation. In the lymphomas, matrix proteins were rarely found. Ewing's sarcoma was variably positive for type IV collagen and laminin, but fibronectin was absent. Extracellular laminin and fibronectin were found in one of two cases of primitive neuroectodermal tumor. In neuroblastoma and ganglioneuroblastoma, the matrix components were rarely found. These results, discrepant with findings in cultured cells, may reflect the altered capacity of tumors to produce these proteins in vitro, which suggests that caution should be exercised in drawing conclusions regarding the nature or histogenesis of tumors from data obtained with cultured tumor cells. Embryonal rhabdomyosarcoma frequently contained all matrix elements in the extracellular space and in a dotlike pattern in the cytoplasm; alveolar rhabdomyosarcoma rarely contained these proteins and never exhibited the dotlike pattern. The frequent finding of matrix proteins in embryonal rhabdomyosarcoma but only rarely in alveolar rhabdomyosarcoma and the unique immunostaining pattern in embryonal rhabdomyosarcoma may prove to be a useful adjunct in the diagnosis of childhood tumors.

TINU syndrome associated with reduced complement levels.

The TINU syndrome (tubulointerstitial nephritis and uveitis) was first described by Dobrin et al. in 1975. Since then, more than 50 cases have been documented each with diverse immunopathogenetic and genetic characteristics. The aim of this report is to describe a case of TINU associated with reduced complement levels. We profile a 48-year-old white female with persistently reduced C4 complement levels during the acute phase of the pathology and with an unaltered immunologic profile. Renal biopsy evidenced a significant lymphocytic interstitial infiltration. Immunohistochemical studies of the interstitium infiltrates was positive for the presence of the T (CD3) markers (CD4 > CD8). Steroid therapy yielded a complete regression of the symptomatology with normalization of the complement levels. We suggest that it is possible to hypothesize that the various immunologic alterations associated with TINU, including the transient reduction complement levels, may be secondary to multiple inflammatory mechanisms which express themselves throughout the pathology.

Beta-2-microglobulin and Helicobacter pylori infection in uraemic dialysed patients.

Chronic gastritis in patients with chronic renal failure may have different causes and mechanisms. Recent observations suggest that severe gastritis often found in uraemic patients might be related to Helicobacter pylori (HP) infection. In chronic gastritis HP has been found in the mucus and on the epithelial cell surface of gastric foveolas. Significant infiltration of the subepithelial gastric layer by polymorphonuclear leucocytes has been described. Moreover, beta-2-microglobulin deposits have been found by immunohistochemical methods in the subepithelial layer of gastric mucosa of uraemic dialysed patients with active chronic gastritis and HP infection. Similar findings have also been demonstrated in gastric biopsies from patients with HP positive active chronic gastritis and normal renal function. Since HP infection is associated with significant leucocyte infiltration, it is hypothesized that the inflammatory process causes the release of beta-2-M from the surface of the leucocytes and its subsequent deposition at gastric level.

Phospholipid hydroperoxide glutathione peroxidase in the normal human kidney: a possible role in protecting cell membranes.

Reactive oxygen species have been implicated in the pathogenesis of tissue injury. It is generally accepted that selenium-glutathione peroxidases form an integrated system defending the living organism against oxidative damage. Phospholipid hydroperoxide glutathione peroxidase (PHGPX) is thought to play a prominent role in preventing lipid peroxidation. Indeed, the function of PHGPX is to reduce the lipophilic substrates in membranes. In the present study, we evaluated the expression of PHGPX in normal human kidney by immunohistochemistry. The enzyme in glomeruli is mainly expressed in podocytes and parietal epithelial cells. In addition, PHGPX antigen was detected in tubule epithelial cells. Therefore, these results suggest that renal epithelial cells possess an important antioxidizing activity related to the presence of PHGPX.

Alpha-1-antichymotrypsin in renal biopsies.

Alpha 1-Antichymotrypsin (alpha 1-AK) and alpha-1-antitrypsin (alpha 1-AT) represent a defense mechanism to protect the tissues from proteolytic enzyme activity. We studied the implication of alpha 1-AK and alpha 1-AT in glomeruli of patients with different nephropathies based on the analysis of 52 paraffin-embedded renal biopsies with alpha 1-AK and alpha 1-AT antisera. The results demonstrate an intense alpha 1-AK glomerular staining in renal biopsies from patients with minimal-change disease, while a minor staining of this protein was found in the other nephropathies. No significant evidence of alpha 1-AT deposits was observed in our cases. Our findings suggest that when alpha 1-AK is lacking in glomeruli the defense mechanisms against proteolytic enzymes may not be efficient enough to protect the glomerular structures and limit the damage. Since alpha 1-AK is a reactant of the acute phase of inflammation, it may be considered as a marker of activity for monocyte-macrophages in glomerular damage.