[Fibrocytes and activated fibrocytes in the healing of an open skin wound]. / Fibrocytes et fibrocytes activés dans la cicatrisation d'une plaie cutanée ouverte.

The microscopic, electron microscopic and immunohistochemical observation of biopsy specimens taken at an early stage, at close and regular intervals (every 4 hours), from open skin wounds created in the pig and the monkey, together with quantitative analysis of the various cell types in the granulation tissue, supports the conception that the activated fibrocyte (fibroblast) originates from the fibrocyte of the wound edges and thus completes some earlier experimental studies. We describe here the various stages of the differentiation of the wound edge fibrocyte into an activated fibrocyte and its proliferation and migration from the edges to the site of the wound. This does not exclude the possibility that local mesenchymal cells take part in the formation of activated fibrocytes. The activated fibrocyte build the collagen of the granulation tissue and then remodel and ensure wound contraction by becoming fibroclasts and myofibroblasts. This article defines the signification of the terms fibrocyte, activated fibrocyte, fibroblast and activated fibroblast.

An atypical aortic atherosclerotic lesion in cynomolgus monkeys during hypercholesterolemia: a protection by smooth muscle cells against advanced lesions?

This study focuses on the fortuitous discovery of an atypical atherosclerotic lesion in four of 49 male adult cynomolgus monkeys (macacus fascicularis) which were maintained for a long time at a high level of hypercholesterolemia, and in seven of 19 female cynomolgus monkeys examined from the second to the 24th week of hypercholesterolemic diet: this lesion was in formation or already mature during this period of diet. This atypical lesion was formed by a collagen and elastic network surrounding synthetic smooth muscle cells without fibrofatty or fibrous plaques. Lipids were occasionally seen in the inner intima. The lesion appeared early (from the third week of diet). Once established, its morphology did not change. It became more extensive, but was not complicated by lipid overload in spite of prolonged, permanent hypercholesterolemia. This response to hypercholesterolemia is interesting because the activity of the smooth muscle cells differs from that observed in the classic lesion: they intervene earlier, their replication is very marked and rapid, their elastin secretion is greater and remains constant over time, and their phagocytic properties are reduced. This experimental study examines the installation and the maintenance of this lesion and raises the problem of its origin.

[Non-atherosclerotic aorta in Cynomolgus after a hypercholesterolemic regimen]. / L'aorte non athéroscléreuse du Cynomolgus après régime hypercholestérolémique.

The authors present a study on atherosclerotic and non atherosclerotic lesions of aortas of Cynomolgus (Macaca Fascicularis) on high fat diet (HFD) (6-12-24 months), after regression and after resumption. At 6 months 2 aortic responses are seen: an edema, deep and superficial clumps of foam cells, few synthetic smooth muscle cells (SSMC) few collagenic fibers--an edema, few superficial foam cells, many SSMC, secreting collagen and elastin. At 12-24 months, after regression and resumption, two aortic lesions are observed: a pronounced atheroma (47 animals) and no atheroma (14 animals). In this case, in the inner part of the aortic wall there are a fibrosis and an elastogenesis, SSMC and just some superficial lipids deposits. These aortic responses of SSMC are certainly the consequence of the environment (the diet) but also the possible consequence of the genetic determinism of SSMC since some animals only present this early, constant fibro-elastic response during this experimental follow up even though all the animals have been subjected to the same lipidic stress.

Optimization of a model of full-thickness epidermal burns in the pig and immunohistochemical study of epidermodermal junction regeneration during burn healing.

In order to obtain a wound model in which healing involved epidermis rebuilding and epidermodermal junction (EDJ) regeneration without involvement of any dermal repair, we optimized a previous model of experimental cutaneous burning with an aluminum bar by testing various conditions of burning associated with different pre- and postburn skin treatments. On the optimized model of full-thickness epidermal burns without any dermal injury, we investigated the kinetics of regeneration of 4 EDJ components, from day 2 to day 23 after burning. The epidermal healing was studied by light microscopy and EDJ regeneration by indirect immunofluorescence with one bullous pemphigoid (BP) serum, antisera to fibronectin and to type IV collagen (Coll IV) and the monoclonal antibody 4C 12-8 to laminin. Histologically, neoepidermis, detected from day 2, appeared as a reepidermization tongue which progressed from the burn edges between the overlying necrotic burned epidermis and the underlying uninjured dermis. Epidermis continuity was found to be restored at day 9. Immunohistochemically, labelling of BP antigen (BPA), Coll IV and laminin extended all along the neo-EDJ, from day 2 to day 23. In contrast, fibronectin labelling was detected only in the proximal and median portions of the neo-EDJ before day 7, then all along the neo-EDJ, from day 7 to day 23. For all the components except Coll IV, the intensity of the labelling beneath the neoepidermis was higher than that of the residual labelling remaining under the necrotic epidermis. Therefore, BPA and laminin regenerated synchronously to neoepidermis whereas fibronectin first regenerated with delay, then synchronously.(ABSTRACT TRUNCATED AT 250 WORDS)

[Collagens of the internal saphenous vein, normal and varicose, as a function of age]. / Collagènes de la veine saphène interne, normale et variqueuse, en fonction de l'âge.

The normal venous vein contains more collagen in the young subject than in the ageing subject. This is confirmed by the decrease of thickness of aged venous wall indicating that the fibrosis present in the aged subject is atrophic in nature. Collagen content of the varicose vein wall remains practically unchanged with age: the varicose vein is a dysplasic vein.

Diabetes mellitus in sand rats (Psammomys obesus): microangiopathy during development of the diabetic syndrome.

The purpose of the study was to investigate the development of microangiopathic complications in North African sand rats with diabetes induced by a long-term standard laboratory diet. Hyperinsulinaemic rats, whether non-diabetic obese or diabetic, developed capillary basement membrane (CBM) thickening in the skin; in insulin-dependent animals, this change was diffuse. Many PAS positive areas were demonstrated in skeletal muscle and myocardium, together with evidence of microangiopathy; the primary myocardial lesion in insulin-dependent disease was ischaemic fibrosis. The kidney was also affected with marked basement membrane thickening in Bowman's capsule and glomerular capillaries; glomerulosclerosis and tubular changes were found in insulin-dependent disease. No evidence of diabetic retinopathy was found, and there was a high incidence of cataract.

Collagen of the normal and the varicose human saphenous vein: a biochemical study.

Various types of collagen (I, III, IV, V) were identified in normal and varicose human saphenous veins using pepsin digestion and cyanogen bromide digestion followed by SDS-polyacrylamide gel electrophoresis. Varicose veins were found to have a higher collagen content than normal veins. This is consistent with the morphological fibrosis which has regularly been described. No essential differences were found in the collagen composition of dilated and apparently healthy portions of varicose veins.

Serum reference values of the Cynomolgus monkey, a model for the study of atherosclerosis.

The usual biochemical parameters were evaluated in 19 Cynomolgus monkeys (male and female), receiving a normal balanced diet. The values were near those reported in man, although certain differences were observed.

Age-related changes in the elastic tissue of the human thoracic aorta.

Thirty human aortas with varying degrees of atheroma graded macroscopically according to the WHO classification were taken at autopsy from subjects of different ages (24-86 years). Study by light microscopy showed aortas with an intact wall (4 subjects, 25-46 years) with a thin intima and regular elastic layers, and aortas with varying degrees of modification of the wall, where the intima was of varying thickness and the elastic fibers showed varying degrees of damage (moderate lesions: 5 subjects, 35-52 yrs; severe lesions: 21 subjects, 26-86 yrs). From each aorta, a 4-cm segment from the tunica media, free of atheromatous lesions, was defatted and subjected to successive treatment with EDTA-Tris, 6 M guanidine-HCl-Tris, 6 M guanidine-HCl-Tris-DTE and collagenase. The residues (EP residues) were subjected to amino acid (AA) analysis and transmission electron microscopy (TEM) study. In the young subject, the AA composition was similar to that of elastin and the TEM images were characteristic of this substance. In the aging subject, an increase in polar AA and a parallel decrease in apolar AA and crosslinks was noted. By TEM, the elastin was seen to be associated with abundant fibrillar material. Trypsin treatment of EP residues gave E residues, whose composition and TEM appearance were similar in all samples, corresponding to the standard composition of elastin and its classic appearance by electron microscopy. We suggest that the fibrillar material removed by trypsin is the morphological reflection of the chemical variations observed in the EP residues. These correspond to contamination of the elastin by a polar protein fraction. This contamination is closely correlated with age but not with the degree of atheroma. Thus the age-related chemical changes in elastin appear to be independent of the onset and evolution of atheromatous lesions. The 10-15 nm diameter of the contaminating fibrillar material suggests that may be the microfibrillar fraction of elastic tissue.

[Experimental atherogenesis: early wall changes in the cynomolgus monkey]. / Athérogénèse expérimentale: modifications pariétales précoces chez le singe cynomolgus.

The early parietal changes in atherogenesis are characterized by: Increase of endothelial permeability with proteoglycans and L.D.L. storage. Lysis of internal elastic lamellae. Penetration into sub-endothelial space of monocytes macrophages and transformation into foam cells. Parietal fibrosis and proliferating smooth muscle cells play a role in the extension of lipid deposit.

Diffuse storage of vegetal wax hydrocarbons of dietary origin. Pathologic and chemical findings in a case.

A 55-year-old man died suddenly, after presenting with unstable angina and an asymptomatic micronodular pulmonary pattern. Autopsy revealed storage of a crystallized fatty substance in the lymph nodes, liver, spleen, adrenal glands, and lungs. In the latter organ, the deposition formed foreign body granulomas, accounting for the radiographic appearance. Mass spectrometry identified the fatty substance as straight-chain saturated hydrocarbons (n-alkanes) of carbon-29 and carbon-31 atoms, which are naturally present in the cuticular wax of many vegetals. The case history and the elimination as causal agent of products manipulated in the patient's work led to the conclusion that the storage was due to excessive consumption of apples, and to a lesser degree of Brussels sprouts. We present the light-microscopic findings and the principal biochemical results. Pathogenic mechanisms are described. As far as we are aware, this is the only observation of vegetal alkane storage to be described to date.

Self-expanding endovascular stent in experimental atherosclerosis. Work in progress.

To investigate the physiologic and histologic responses induced by the self-expanding endovascular prosthesis, rabbits subjected to a combination of high-cholesterol diet and intravascular trauma underwent stent implantation. The results were compared with those obtained with the placement of stents in the healthy aortas of rabbits. Stents in healthy aortic tissue led to stent intimalization, previously reported in canine studies. For stents placed in animals subjected to a high-cholesterol diet but no intimal trauma, it was found that the stent was not the source of atherogenesis. Stents placed in atheromatous plaque were found to radially compress plaque with time and to stimulate for formation of a fibrotic crust. The results suggest that the self-expanding stent protects against progressive encroachment of the vessel lumen by atherosclerotic tissue.

[Cerebral gliomatosis. An anatomoclinical case]. / La gliomatose cérébrale. Une observation anatomoclinique.

Gliomatosis cerebri is a glial neoplastic process. It is diffusely distributed through brain structures whose anatomical configuration remains intact. Clinical diagnosis of this rare disease is difficult. The symptoms are varied and biological and radiological data are not specific. The case reported shows the characteristic features of the disease. Diagnosis was possible only on autopsy, in spite of several previous clinical and biological investigations and nuclear magnetic resonance study.

[Scintigraphic detection of pheochromocytoma metastases. Morphologic control apropos of a case]. / Détection scintigraphique des métastases de phéochromocytomes. Contrôle morphologique à propos d'un cas.

The authors report a case of malignant pheochromocytoma. They explain the difficulties of the diagnostic of malignancy which can only be confirmed by metastases. Radioisotope scanning with I131 metaiodobenzyl guanidine is the best available method to locate the primary tumor and the metastases. The results of radio isotope scanning are compared to the ultrastructural study.

[Association of an adenoid cystic epithelioma with a clear cell carcinoma of the palate]. / Association d'un épithélioma adénoïde kystique et d'un carcinome à cellules claires du palais.

An infrequent polymorphous minor salivary gland tumor is described. It involved the palate and later invaded the upper jaw. The morphologic features are those of both adenoid cystic carcinoma and clear cell carcinoma. The clinical course, the cellular admixture of tumour components, and the immunohistologic results allow us to propose that clear cell carcinoma originating from adenoid cystic carcinoma offers the worst prognosis.

Fibroblasts in dermal tissue repair. Electron microscopic and immunohistochemical study.

The cellular dynamics of dermal regeneration were studied in nonsutured cutaneous wounds of female pigs and monkeys with electron microscopy and immunohistochemistry to demonstrate the origin and the development of fibroblasts forming granulation tissue. The results indicate that fibroblasts do not originate from histiocytes but from resting fibroblasts in the wound margins. These resting fibroblasts first become undifferentiated mesenchymal cells termed "X" cells. The "X" cells then multiply, migrate, and invade the wound defect in approximately 3 days, transforming into highly active fibroblasts. The active fibroblasts are endowed with the capacity of further transformation to fibroclasts and myofibroblasts. The latter two cell populations then effectively cause remodeling of newly formed tissue and contraction of wound margins.

The elastic tissue of the skin. A comparison of spontaneous and actinic (solar) aging.

In order to separate the changes of actinic damage from those of simple aging, we studied the elastic fibers in low and high sun-exposed skins of normal subjects at different ages. Low sun-exposed skin shows chronologic aging lesions only. These begin at age 30 with a disappearance of oxytalan fibers and with some abnormalities in the reticular and deep dermis; at age 40, aging changes are established: no oxytalan fibers, marked abnormalities, and lysis of elaunic and elastic fibers. In high sun-exposed skin, age-related lesions also occur but are associated with more or less precocious elastotic degeneration in reticular and deep dermis. Both types of aging fibers are revealed by the antielastin antibody HB 8, disappear with elastase, but resist collagenase. Actinic elastosis clearly originates from elastin. The two types of change differ in electron microscopic appearance: with spontaneous aging, elastic fibers are disintegrated (loose and porous fibers); in actinic damage, elastotic fibers are thicker and have accentuated microfibril dense masses. The age-associated lesions could be due to the activity of protease of fibroblastic origin whereas the elastotic degeneration is probably due to the actinic stimulation of fibroblasts.