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Biomedical subjects

R Lagacé

Publications and source records attributed to R Lagacé.

At least 37 records · Page 2Linked to original sources

Stromal myofibroblasts in primary invasive and metastatic carcinomas. A combined immunological, light and electron microscopic study.

A series of 23 primary invasive and 7 metastatic carcinomas was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunofluorescence (IF), the latter employing an anti-actin antibody. The results were correlated with macroscopic features such as retraction and consistency. Stromal cells rich in actin, readily identified by IF in firm and retracted carcinomas, were rare or absent in neoplasms lacking these features. TEM established the myofibroblastic nature of these stromal cells. Alternate sections (LM, IF) of each neoplasm demonstrated that myofibroblasts were more numerous in "young" mesenchymal stroma than in densely sclerotic areas. The connective tissue adjacent to intraductal mammary carcinoma lacked myofibroblasts, suggesting that epithelial stromal invasion is required to evoke a myofibroblastic stromal response. Myofibroblasts which possess synthetic (type III collagen) and contractile properties may well contribute to the firm consistency and retraction which characterize many carcinomas. The induction of myofibroblasts might represent an important host stromal response directed toward containment of invasive and/or metastatic carcinoma. This response may be especially important in neoplasms with weak antigenicity and/or slow doubling times.

Actins↗

[Polypoid pseudosarcomatous carcinoma. Histogenesis with evidence of myofibroblastic response (author's tranls)].

Three polypoid pseudosarcomatous carcinomas (PPSC) of the oesophagus, larynx, and urinary bladder were studied by electron microscopy to determine their histogenesis and the cellular associations which might contribute to their relative clinical benignity. In addition to a polypoid, exophytic growth, the three shared similar light microscopy features : surface ulceration, a minimal invasive epithelial component and prominent spindle-cell proliferation in association with reticulin and collagen. Three cell types were identified ultrastructurally : 1. - spindle and polygonal cells demonstrating tonofilaments and plasma membrane specialization, denoting an epithelial origin; 2. - cells identical to the first type, but with cytoplasm containing intracellular collagen ; and 3. - myofibroblasts characterized by a rough endoplasmic reticulum, prominent Golgi complexes and well formed bundles of myofilaments. The latter constituted the principal cellular component of the tumors. These findings demonstrate that the stroma of the PPSC is dominated by myofibroblasts, which probably synthesized much of the collagen associated with these neoplasms. It is suggested that the myofibroblasts signify an expression of host reactivity to the invasive carcinoma and constitute a beneficial response which contains and restricts local and vascular invasion by neoplastic cells, this contributing to the relative benignity of the neoplasms.

Aged↗

[Cardiovascular effects of cigarette smoke in the rat. Aortic endothelial and myocardial capillary permeability in the rat].

The permeability of aortic endothelium and myocardial capillaries was examined in 72 Sprague-Dawley rats (approximately 350 g) using the diffusion tracer peroxidase. Animals were subjected to cigarette smoke for periods of 1 day (acute effects), 2 weeks (sub-acute effects) and 15 weeks (chronic effects) and were sacrificed 5 minutes or 8 hours after smoking. Peroxidase was not generally present at the sub-endothelial level in the aortic endothelium of control animals and sham-smokers. However, in smokers, the increase in peroxidase permeability is proportional to the smoking period. Moreover, in these smokers we observed junctional and subendothelial vacuolar dilatations which correspond to degenerative morphologic changes. Cigarette smoke has a different effect on the right ventricle. Endothelial permeability of the myocardial capillaries increases in animals subjected to cigarette smoke for 1 day and those who smoked for 2 weeks sacrificed 5 minutes after smoking. This increase in permeability is not related to the significant morphologic changes observed in the myocardium and endothelial capillaries. However, the myocardial endothelial capillaries, the sub-endothelial space and the adjacent interstitial space were generally free of peroxidase in animals subjected to cigarette smoke for 15 weeks and in those smoking for 2 weeks sacrificed 8 hours later. An adaptive phenomenon to the effects of cigarette smoke appear to exist in the myocardial endothelium capillaries contrary to that which is observed in the thoracic aorta.

Animals↗

Myofibroblasts in soft tissue sarcomas.

A series of 129 soft tissue sarcomas was examined ultrastructurally to determine in which neoplasms and to what extent myofibroblasts could be demonstrated. Twenty cases of fibromatosis and fasciitis served as controls. Myofibroblasts were identified in all 30 cases of malignant fibrous histiocytoma and all 4 cases of well-differentiated sclerosing liposarcoma. Though most numerous in areas of desmoplasia, in no instance did myofibroblasts constitute the dominant cellular constituent of either neoplasm. Myofibroblasts were identified with lesser frequency and in smaller numbers in fibrosarcoma, synovial sarcoma, malignant hemangiopericytoma and neuroblastoma. None were observed in a wide assortment of diverse sarcomas in which desmoplasia was not a feature. In comparison each lesion judged by light microscopy to represent either fibromatosis or fasciitis was composed principally of myofibroblasts. The demonstration of abundant myofibroblasts within a soft tissue lesion which has been subjected to wide sampling strongly suggests a benign proliferative process as opposed to a malignant neoplasm. It is hypothesized that myofibroblasts observed within collagenized regions of soft tissue sarcomas may constitute an expression of host response to neoplasia.

Fibroblasts↗

On the pathogenesis of sclerosis and nodularity in nodular sclerosing Hodgkin's disease.

Ten cases of nodular sclerosing Hodgkin's disease involving lymph nodes were studied by electron microscopy to determine the ultrastructural composition of the nodule-stromal interphase and the collagenized regions. In addition to a few lymphocytes, rare eosinophils and neutrophils, abundant filamentous and granular electron dense material, collagen fibers and myofibroblasts were observed in all instances. Since myofibroblasts possess contractile and synthetic properties, it is likely they contribute to the retraction and sclerosis which together represent one of the morphologic hallmarks of the disease. The dense fibrosis and contractile state of such tissue may constitute a beneficial host response to contain and limit local and vascular invasion by the neoplastic cellular population, thus contributing to the relative benignity of this form of Hodgkin's disease.

Adolescent↗

Effects of cigarette smoke on rat thoracic aorta.

Using the fine structural macromolecular tracer horseradish peroxidase (HRP) the permeability of thoracic aorta was studied in 72 male Sprague-Dawley rats. Rats smoked for 1 day (acute effect), 14 days (subacute effect) and 15 weeks (chronic effect). Thoracic aorta sections from control rats and sham smokers were free of HRP reaction product. In smokers' thoracic aortas, permeability to peroxidase increased proportionately to the increase in length of the smoking period. Furthermore, smokers' thoracic aortas exhibited focal vacuolar dilatations (subendothelial blebs) and an increased number of subendothelial macrophages.

Animals↗

Myxoid variant of malignant fibrous histiocytoma: ultrastructural observations.

The ultrastructural findings in 4 cases of the myxoid variant of malignant fibrous histiocytoma (MFH) are described. Although this neoplasm is characterized by a high rate of local recurrence, the overall prognosis is considerably better than the usual nonmyxoid MFH. The neoplasm is composed of an admixture of round, stellate and multinucleated giant cells within a myxoid and well-vascularized stroma. Electron microscopy demonstrated four principal cell types: a primitive mesenchymal cell, spindle cells of fibroblastic and histiocytic nature, and multinucleated giant cells. These observations complement the light microscopic features but probably are insufficient to differentiate critically this entity from other myxomatous lesions of mesenchymal soft tissue such as myxoma, pseudosarcomatous fasciitis, myxoid liposarcoma. The polymorphic cellular composition lends support to the concept that the neoplasm is probably derived from a primitive multipotent mesenchymal cell capable of structural and functional modulation toward more cytodifferentiated forms.

Diagnosis, Differential↗

Myxoid liposarcoma. An electronmicroscopic study: biological and histogenetic considerations.

Ten myxoid liposarcomas (ML) were studied ultrastructurally in an attempt to determine the histogenesis of this neoplasm and structural associations which might contribute to their relatively benign clinical behavior. The findings were compared with normal and neoplastic adipose tissue. Three cell types were observed, i.e., "primitive" mesenchymal cells, intermediate cell types, and lipoblasts at various stages of development. The principle differences between the lipoblastic elements were the number and the size of intracytoplasmic fat vacuoles, the development of basement membrane-like material, micropinocytotic vesicles along the plasma membrane and the quantity and pleomorphism of mitochondria. The tumor vasculature was complex but consistently demonstrated a multilayered basal lamina. This finding has been described in neoplasms associated with a relatively good prognosis. This study demonstrates that the better differentiated lipoblasts in ML share some features with normal brown fetal fat and hibernoma. It is, thus, suggested that ML may be derived from brown adipose tissue.

Adipose Tissue, Brown↗

Desmoplastic fibroma of bone. An ultrastructural study.

The ultrastructure of three cases of desmoplastic fibroma of bone is presented. The lesion is principally characterized by myofibroblasts admixed with lesser numbers of fibroblasts and primitive mesenchymal cells. Thus, the cellular composition is similar to that described in a variety of nonneoplastic proliferative processes of soft tissue. It is postulated that the myofibroblastic proliferation develops in response to unknown factors acting on marrow fibroblasts or primitive mesenchymal cells.

Adolescent↗

Myofibroblasts in the stroma of invasive and metastatic carcinoma: a possible host response to neoplasia.

After observing the presence of numerous stromal myofibroblasts in scirrhous mammary carcinomas, a series of invasive and metastatic carcinomas from diverse sites was examined by electron microscopy to determine whether myofibroblasts might also be present in their stroma. Myofibroblasts were identified in each instance and were most abundant in neoplasms which were hard, sclerotic, and retracted. This finding suggests that myofibroblasts represent a component of the stromal reaction to many carcinomas and contribute to the desmoplasia and retraction which characterize many of these neoplasms. The host commands several responses to neoplasia. As a result of the expression of tumor-associated antigens, the immune system contributes lymphocytes, macrophages, and antibodies, a reflection of immunologic surveillance against neoplasia. In contrast to experimental systems tumor neoantigens are poorly expressed or even lacking in many human neoplasms; thus, the immune system may be weakly stimulated or not activated at all. Tumor neovascularization induced by a tumor-angiogenesis factor represents a second host response, possibly deleterious, for it may facilitate tumor dissemination. The stromal myofibroblast reaction to many invasive and metastatic carcinomas may constitute a third, albeit more primitive response. The density of collagen produced and contractile state of such tissue may signify an attempt by the host stroma to contain the neoplasm and impede vascular invasion. If so, myofibroblast induction may complement immune surveillance or constitute a separate mechanism of response to invasive neoplasia in man.

Carcinoma↗

Paraganglioma of the filum terminale.

An unusual tumor arising in the filum terminale is described. The clinical data revealed an extensive and slowly growing lesion. The histologic picture was characterized by a proliferation of lobules and sheets of regular cells within a rich vascular network. Electron microscopic studies showed light and dark cells with sustentacular extensions. Typical neurosecretory granules were observed in both cell types, establishing the diagnosis of para-ganglioma. The glomus coccygeum could be the site of this tumor.

Cauda Equina↗

Malignant fibrous histiocytoma. Clinicopathologic and ultrastructural study of 12 cases.

The clinical and pathologic findings of 12 cases of malignant fibrous histiocytoma of the soft tissues are presented. The mean age of the patients (eight males and four females) was 64 years, and there was a strong predilection for localization in the extremities (10 cases). The lesion is of rather low-grade malignancy, with metastases in only a minority of cases (three cases) but with nonetheless a marked tendency for local recurrence (nine cases). Histologically, the essential feature of the tumor is its biphasic composition with both histiocytic and fibroblastic components, the latter showing a characteristic storiform pattern. In addition, a variable number of xanthomatous cells and multinucleated giant cells were observed. Ultrastructural studies confirmed the presence of the aforementioned cells and in addition revealed a primitive mesenchymal cell. It is suggested that this cell may be a primitive histiocyte from which the two main cellular components of the tumor arise.

Adult↗

Pseudocyanotic pigmentation of the skin induced by amiodarone: a light and electron microscopic study.

An unusual bluish discolouration of the nose was noticed in a woman 9 months after she had begun treatment with a coronary vasodilator, amiodarone hydrochloride. Cutaneous biopsies of the nose were obtained 6 and 9 months later for light and electron microscopic studies. In the dermis were histiocytes containing cytoplasmic yellow-brown granules with histochemical properties of melanin and lipofuscin. Ultrastructurally the granules appeared as lysosomal membrane-bound dense bodies similar to lipofuscin. Similar granules were observed at diascopy in both corneas. The pathogenesis is obscure. A storage disease involving the drug or its metabolites cannot be ruled out. Another possibility is that amiodarone accelerates the normal cellular autophagocytosis, resulting in increased production of lipofuscin, which then accumulates in lysosomes because of a deficiency in lipolytic enzymes.

Amiodarone↗