Background. A number of experimental studies have substantiated changes in angiogenesis and in laminin/ laminin‐receptor interactions during tumorigenesis and tumor progression. However, these observations have never been verified objectively in tissues from a well‐defined model of tumor progression. Methods. Tissues from 97 proliferative lesions of the melanocyte lineage defining distinct steps in tumor progression were investigated immunohistochemically for changes in angiogenesis and expression of the laminin receptor (67‐kilodalton molecule). Results. Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed “nevi with ADMA”), and these changes persisted during transformation. Progression to primary melanomas was accompanied by a high microvessel number and progression to metastases by another significant increase. The number and diameter of microvessels were significantly higher at the lesion base than at the adjacent dermis of primary melanomas and higher in the lesion than in the adjacent tissue of metastatic foci. Expression of the laminin receptor, evaluated as percentages of positive lesions and positive cells per lesion, underwent upregulation in the course of progression. Changes in expression were associated mostly with nevi with ADMA, transformation, and deepening of the tumors into the dermis. Conclusions. These in situ data suggest that more frequent interactions between melanocytic cells and their microvasculature via adhesion protein laminin occur during tumor progression.

Skin and/or liver biopsy specimens were obtained from the following patients: 15 anti-hepatitis C virus (HCV), HCV RNA-positive patients and 3 anti-HCV, HCV RNA-negative patients with type II mixed cryoglobulinemia (MC); 7 anti-HCV, HCV RNA-positive patients with chronic active liver disease (CALD); 5 anti-HCV, HCV RNA-negative patients with noncryoglobulinemic vasculitis; and 7 anti-HCV, HCV RNA-negative patients with lichen ruber planus. A pool of murine monoclonal antibodies (MAbs) developed against c22-3, c33c, and c100-3 proteins was used to detect HCV-related antigens (Ags) by indirect immunohistochemistry. Acid electroelution (AEE) of tissue sections was performed to enhance the sensitivity of the immunohistochemical method. In anti-HCV-positive MC patients, specific HCV-related Ags were detected in the small vessels of the skin and in the cytoplasm of hepatocytes. Prior AEE of biopsy sections allowed detection of HCV Ags in 6 of 15 (40%) skin biopsy and in 9 of 14 (64.3%) liver biopsy specimens. HCV immunoreactive deposits in the skin displayed two immunohistochemical patterns: (1) coarse intraluminal material associated with dermal inflammatory infiltrates and intravascular deposition of eosinophilic hyaline material; and (2) reactivity confined to the vessel wall in the context of an apparently normal tissue. Immunoglobulin (Ig) G and IgM deposition in the skin showed immunohistochemical features comparable with those found for HCV Ag deposits.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to confirm the clinical efficacy of oxerutins by evaluation of venous parietal tone and microvascular perfusion in a double-blind, randomized, placebo-controlled study. The study included 60 patients. Venous tone was evaluated by air-plethysmography (APG) in patients with venous insufficiency (CVI). Forty patients were treated with oxerutins and 20 with placebo for 4 weeks. The dose of the first 2 weeks was higher than that of the following 2 weeks. The age range was between 18 and 65 years. Randomized patients received treatment (oxerutins or placebo) according to the grade of CVI. Patients with grade I CVI received 2 g/day in the first 2 weeks of treatment and 1 g/day in the following weeks. Patients with grade II CVI received 3 g/day in the first 2 weeks and 2 g/day in the following 2 weeks. Visits were scheduled at baseline time (visit 1), at 2 weeks (visit 2) and at 4 weeks (visit 3). They were assessed with the following: (1) APG; (2) light reflection rheography (LRR); (3) capillaroscopy; (4) liquid crystals thermography. CVI signs/symptoms--heavy legs, edema, paresthesia, and cramps--were evaluated following a 4-point rating scale (0 = no symptom; 3 = severe symptoms). At visit 3 a final opinion on efficacy was provided by both patients and investigators, based on a 4-point scale (none, fairly good, good, excellent). The two groups were homogeneous for age, sex, and clinical distribution. The changes in venous capacity, were significant (p<0.01) in the oxerutins group at visits 2 and 3; values in the placebo group remained unchanged. The changes in LRR were significant in the treatment group at visits 2 (p<0.05) and 3 (p<0.01); values in the placebo group remained unchanged. Changes in temperature were significant in the oxerutins group at visits 2 (p<0.05) and 3 (p<0.01); changes in the placebo group were not significant at the end of the study. Capillaroscopy showed an improvement in patients treated with oxerutins. The results of the analysis of signs/symptoms favored active treatment. The overall effects of oxerutins were significantly better than the effects of placebo. Considering both noninvasive tests and clinical evaluation, oxerutins is effective in controlling chronic venous hypertension, without side effect, and with good tolerability.

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Psoriatic lesions are relatively frequent in patients with chronic liver disease. Furthermore, therapy with interferons tends to exacerbate the symptoms. The pathogenesis of psoriatic lesions is unclear. An important question is whether such lesions may be linked to the underlying chronic liver disease in these patients, or whether they are incidental manifestations of psoriasis vulgaris. We collected biopsy specimens from involved and uninvolved skin areas of chronic liver disease patients with psoriatic manifestations, as well as from psoriasis vulgaris patients, and investigated the patterns of integrin adhesion receptors by means of immunohistochemical methods. Integrin expression is known to be characteristically altered in psoriasis vulgaris. We found some of these changes in chronic liver disease psoriatic lesions — namely pericellular redistribution and suprabasal expression of the basement membrane receptor α6β4 and of the intercellular integrins α2β1 and α3β1. However, psoriasis vulgaris causes two other typical changes: One is the induction of the prototype fibronectin receptor α5β1, and the other is the alteration of integrin expression in areas of the epidermis that are macroscopically normal. These two changes were not found in chronic liver disease psoriasis biopsy specimens in 14 patients investigated. Thus integrin expression may be useful in differentiating chronic liver disease psoriatic lesions from psoriasis vulgaris lesions. Even though the two types of lesions are indistinguishable on inspection or by their histological features, they may be caused by distinct pathogenetic mechanisms. It remains to be seen whether the underlying chronic liver disease has a role, albeit indirect, in such mechanisms. (Hepatology 1994;20:56–65.)