The evolution of the atheromatous plaque: ultrastructural evidence.

Our understanding of endothelial physiology is overdue compared with other areas of study. For too many years the complex mysteries of this thin single-layered cellular lamina covering the whole of the vascular network, from the large conduction vessel to the smallest resistance and diffusion vessel, have been hidden by an organ-based science more focused on organ pathology than on ultrastructural physiopathology. We tried to follow chronologically the alteration stages of this system of membranes in relation to the development of the atherosclerotic plaque in human biopsy.

One case of immunotactoid glomerulopathy: morphological-ultrastructural aspects.

Starting from a group of 736 renal biopsy patients, evaluated by ultrastructural studies over a period of 22 years, the authors present a rare case of immunotactoid glomerulopathy, suggesting that these forms, until a few years ago considered in the same group as fibrillary glomerulonephritis, are in fact a separate entity; moreover, they may represent a very early manifestation of plasmacellular dyscrasia still at the initial stage.

Haemodynamic and ultrastructural observations on the rat liver after two-thirds partial hepatectomy.

Rat liver ultrastructure was investigated after partial hepatectomy (PH), by scanning and transmission electron microscopy. Portal pressure was monitored before and after PH and, after killing performed at 6, 12, 24, 48 h and 10 d, regenerating livers were fixed by portal vein perfusion under haemodynamic conditions identical to those existing in vivo. An early and persistent increase in portal pressure after PH was found (P < 0.01 for normal vs sham-operated controls). Ultrastructural study showed sinusoid dilatation and disappearance of the sieve-plate arrangement of small endothelial pores, thus leaving the parenchymal liver cell surface directly exposed to portal blood. Widening of sinusoids, endothelial fenestrations, intercellular spaces and spaces of Disse, was accompanied by dilatation of bile canaliculi. At 10 d, liver ultrastructure had returned to normal. Our observations suggest that a rise in portal pressure, as a consequence of PH, may be related to the observed ultrastructural changes in the liver.

Human herpesvirus 7 infection induces profound cell cycle perturbations coupled to disregulation of cdc2 and cyclin B and polyploidization of CD4(+) T cells.

Human herpesvirus 7 (HHV-7) infection of both primary CD4(+) T lymphocytes and SupT1 lymphoblastoid T-cell line induced a progressive accumulation of cells exibiting a gap 2/mitosis (G2/M) and polyploid content coupled to an increased cell size. The expression of both cyclin-dependent kinase cdc2 and cyclin B was increased in HHV-7-infected cells with respect to the uninfected ones. Moreover, the simultaneous flow cytometric analysis of cyclin B and DNA content showed that cyclin B expression was not only increased but also unscheduled with respect to its usual cell cycle pattern. However, the levels of kinase activity associated to cdc2 were decreased in HHV-7-infected cells with respect to uninfected cultures. To elucidate the origin of the enlarged HHV-7-infected cells, extensive electron and confocal microscopy analyses were performed. Membrane fusion events associated to cytoplasmic bridges, which characterize the formation of syncytia, were never observed. On the other hand, analysis of serial sections of the same cells strongly suggested that enlarged HHV-7-infected cells contained a single polylobated nucleus. This was confirmed by flow cytometry analysis performed on nuclei isolated from HHV-7-infected cells, which showed multiple peaks with a DNA content >4n. Taken together, these data indicate that giant cells, which represent the hallmark of in vitro HHV-7 infection, arise from single CD4(+) T cells undergoing a process of polyploidization.

Birbeck granules: contribution to the comprehension of intracytoplasmic evolution.

We investigated the ultrastructure of Birbeck granules which are found in some malignant histiocytoses such as histiocytosis X, Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma of the bone and self-healing reticulohistiocytosis. The research is based on the systemic study of Birbeck granules, from their formation to intracytoplasmic development, examining with the electron microscope at regular intervals ultrathin sections derived from biopsies of two cases of Langerhans cell histiocytosis.

Spontaneous cell fusion in macrophage cultures expressing high levels of the P2Z/P2X7 receptor.

Mouse and human macrophages express a plasma membrane receptor for extracellular ATP named P2Z/P2X7. This molecule, recently cloned, is endowed with the intriguing property of forming an aqueous pore that allows transmembrane fluxes of hydrophylic molecules of molecular weight below 900. The physiological function of this receptor is unknown. In a previous study we reported experiments suggesting that the P2Z/P2X7 receptor is involved in the formation of macrophage-derived multinucleated giant cells (MGCs; Falzoni, S., M. Munerati, D. Ferrari, S. Spisani, S. Moretti, and F. Di Virgilio. 1995. J. Clin. Invest. 95:1207- 1216). We have selected several clones of mouse J774 macrophages that are characterized by either high or low expression of the P2Z/P2X7 receptor and named these clones P2Zhyper or P2Zhypo, respectively. P2Zhyper, but not P2Zhypo, cells grown to confluence in culture spontaneously fuse to form MGCs. As previously shown for human macrophages, fusion is inhibited by the P2Z/P2X7 blocker oxidized ATP. MGCs die shortly after fusion through a dramatic process of cytoplasmic sepimentation followed by fragmentation. These observations support our previous hypothesis that the P2Z/P2X7 receptor is involved in macrophage fusion.

Cholesterol vesicles in areas of gastric metaplasia of gallbladder epithelium.

Gastric metaplasia is a frequent epithelial change in gallbladder of lithiasic patients. Particles consistent with cholesterol-containing vesicles were searched in areas overlying gastric metaplastic cells, in gastric metaplastic cells, in areas overlying normal-looking epithelial cells and in normal-looking epithelial cells in 25 patients with radiolucent calculi and 10 control patients undergoing cholecystectomy for other reasons. Important trends were found confirming the peculiar role of mucous layer adherent to metaplastic gallbladder epithelium in beginning the nucleation process and interesting pictures concerning the formation of uni- and multilamellar vesicles in these "nucleating areas" were seen.

Histological findings in gastric mucosa in patients treated with non-steroidal anti-inflammatory drugs.

AIMS: To identify distinguishing and general histological features related to the use of non-steroidal anti-inflammatory drugs (NSAID). METHODS: Slides from gastric antral biopsies of 50 patients with osteoarthritis taking NSAID were compared with slides from antral biopsies of 50 control cases matched for age, sex, and race. Semithin sections stained with toluidine blue were used. RESULTS: Chronic gastritis was seen in 76% of the patients taking NSAID and in 58% of the control cases; active inflammation was detected in 10% of the NSAID treated patients and in 24% of the control cases, and it appeared closely related with Helicobacter pylori infection. Some histological features common to all slides of patients taking NSAID were recognised. These consisted of focal erosions of the gastric epithelium and macroerosions, and they seemed to represent successive steps of a process of "desquamation". CONCLUSIONS: Some distinguishing morphological aspects appeared prominent; it is suggested that these may be related to the pathogenesis of NSAID linked peptic ulceration. On the other hand, epithelial damage due to NSAID appears very different from that due to Helicobacter pylori, another important factor involved in the aetiopathogenesis of peptic disease.

Increased sinusoidal wall permeability and liver fatty change after two-thirds hepatectomy: an ultrastructural study in the rat.

Accumulation of lipids in the hepatocyte cytoplasm after partial hepatectomy (PH) has long been recognized, but the mechanism behind this phenomenon is still poorly understood. In this study, rats subjected to a standard two-thirds PH showed early and marked increase in portal venous pressure (P < .01). On scanning electron microscopy, the regenerating liver fixed by portal perfusion under hemodynamic conditions identical to that found in vivo during the first 24 hours showed a significant (P < .01) 10-fold increase in the sinusoidal wall porosity (percentage open area by fenestrations). This was paralleled by the disappearance of the sieve-plate arrangement of small fenestrations and by a significant decrease in the number of fenestrations per micrometers squared of sinusoidal surface at 6 (P < .01) and 12 hours (P < .05). In addition, there were major changes in the frequency and distribution of all three classes of fenestrations. At 6 and 12 hours, there was a marked decrease of small class 1 fenestrations and a marked increase of intermediate class 2 fenestrations and large class 3 fenestrations (P < .0001). A concurrent accumulation of lipid droplets in the hepatocyte cytoplasm produced a 20-fold increase in the hepatocyte total lipid volume. A statistically significant linear correlation (r = 0.907; P < .01) was found between the amount of intracellular lipids and the data quantitating the changes in porosity of liver sinusoids at 24 hours. It is concluded that an increased sinusoidal wall permeability to lipids may be the primum moves in the pathogenesis of transient liver fatty change after PH in the rat.

Familial interstitial nephropathy without hyperuricemia.

Progressive hereditary nephropathy is described in 6 members of a single family. Renal biopsies, performed in 3 patients, revealed tubular atrophy, interstitial fibrosis, and lymphomonocytic infiltration associated with severe vascular lesions. These features were disproportionately serious when related to age, arterial pressure, and renal function. Similar familial nephropathy has been reported in the literature, generally in association with gout or asymptomatic hyperuricemia. The patients described here had normal blood concentrations of uric acid. It is proposed that the members of the present group of patients are suffering from the same interstitial nephropathy as that described in the literature and that the hyperuricemia found by other investigators is coincidental and does not play a pathogenetic role.

Ultrastructural patterns of Helicobacter pylori.

Ultrastructural morphology of the bacterial bodies was studied in 40 Helicobacter pylori positive cases. Two bacterial patterns were identified, which were associated with different modes of contact with the epithelial cells and possibly with different stages of the natural history of the infection.

Structural changes of duodenum brush border in lung cancer patients treated with cisplatin plus etoposide.

The effects of cisplatin plus etoposide chemotherapy (PE) on the structure of proximal intestine villi and brush border were investigated in 10 patients with lung cancer. The day before starting chemotherapy (time 1); 8 days after its initiation (time 2), and one month after the 3rd course of PE (time 3) they underwent esophagogastroduodenoscopy and three biopsies were taken from the descending duodenum. Intestinal villi were examined by light microscopy; brush border by transmission electron microscopy. No significant histological changes of villous pattern were observed at times 2 and 3. The height of microvilli was reduced in seven patients at time 2 (P < 0.05). Microvilli abnormalities (i.e. rarefaction and/or heterogeneity in their height) were present in nine patients at time 2 (P < 0.05). Brush border appearance at time 3 did not differ from that at time 1. PE chemotherapy seems to have short-term toxic effects on small intestine brush border, but does not cause chronic enteropathy.

Acquired ciliary defects in bronchial epithelium of patients with chronic bronchitis.

In order to quantify and classify ciliary changes of bronchial epithelium in chronic bronchitis, an ultrastructural study on biopsy specimens of 30 patients submitted to bronchoscopy was performed. Fourteen patients were affected by endoscopically and clinically confirmed chronic bronchitis, 8 showed an endoscopic picture of chronic bronchitis but without the clinical features of this pathology, 8 were free of chronic bronchitis. The mean percentage of abnormal cilia in control subjects (1.9 +/- 1.0%) was significantly lower than in patients either with only 'endoscopic' chronic bronchitis (5.7 +/- 2.6%; p less than 0.001) or with 'clinical' chronic bronchitis (14.8 +/- 15.9%; p less than 0.05). Like the ciliary body, the ciliary tip can also show some abnormalities. It is possible to subdivide them in two types: (1) ciliary membrane blebs; (2) ciliary membrane extrusions, variously shaped and sized, with homogeneous content. Bronchial cilia abnormalities become more serious as soon as the clinical picture worsens and this is likely to contribute to the impairment of the mucociliary clearance in chronic bronchitis patients.

Gastric metaplasia in duodenal bulb and Campylobacter-like organisms in development of duodenal ulcer.

Multiple biopsies were taken from 50 patients with endoscopic appearance of duodenitis in order to study the relationship between gastric metaplasia in duodenum and the presence of Campylobacter-like organisms (CLOs) and the development of duodenal ulcer disease. Metaplasia was found in at least one biopsy specimen from 46 of the 50 patients; CLOs were seen in 25 of the 50 patients, only in metaplastic areas. In four cases a "transitional epithelium" with the presence of cells containing few apical mucoid granules and absorbent-type brush border as well as goblet cells was seen. In two cases, this epithelium was colonized by a small number of CLOs. Gastric heterotopia appears to be a rare condition.