Asunto(s)

Asunto(s)

RESUMEN

The neurocristopathies, originally defined in 1974 as a category of diseases arising in neural crest development are reviewed as to their current status. Accompanying the great advances in neural crest ontogeny, there has been an increase in the number and variety of neurocristopathies, particularly in the definition of craniofacial syndromes derived from the cranial crest mesectoderm. Molecular biology and genetics have added new dimensions in defining interrelationships between a number of entities. Environmental teratogens that cause neurocristopathies are also discussed. Neurocristopathy as a pathogenetic concept should continue to be useful as a structural framework for future investigations.

Asunto(s)

RESUMEN

The fine structure and ultrastructure of the anterior descending coronary artery were studied in a series of perinatal piglets at 1 week prior to birth, and at 8, 24, 72 and 168 h after birth. In the anterior descending coronary artery, at or just distal to the branch point of the left circumflex artery, early plaque-like intimal lesions were present in the majority of animals. These consisted of subendothelial edema, fragmentation and dissolution of the internal elastic lamella, and the appearance of intimal myoid cells known as modified smooth muscle cells (MSMCs). These changes were present in all piglets at and before 8 h of age. They persisted and progressed during the first week of life in about half of the piglets. Beginning at 72 h and continuing through 168 h, there was an increase in MSMCs and the appearance of fibroblasts. Both fibroblasts and MSMCs were associated with the elaboration of dense collagen fibrils. Foamy macrophages appeared within the subendothelial intima having the appearance of lipophages. While the prevalence of these changes at birth indicates that they may be part of normal development, their persistence in half the piglets and structural features suggest reaction to intimal injury beginning prenatally. The lesions may be precursive of coronary atherosclerosis later in life and may parallel the early stages of atherogenesis in humans.

Asunto(s)

RESUMEN

Newborn piglets were subjected to 45 min of sustained norepinephrine-induced hypertension and then monitored for 4 hr at baseline conditions. They were then sacrificed and the anterior descending coronary artery was serially sectioned for study by light and electron microscopy. Other groups were sacrificed after 72 and 168 hr of baseline conditions. Changes were limited to the endothelium and subendothelial intima of the most proximal segment of the anterior descending coronary artery. As similar changes are normally present in perinatal piglets, the experimental animals were compared with sham-operated controls to determine if there was a modification of the naturally occurring congenital lesions. Although the prevalence of coronary lesions in control and experimental animals was not significantly different, the experimental groups showed unique features. At 4 hr, there was marked intimal edema and disruption of the endothelium with fragmentation and dissolution of the internal elastic lamina. There was selective invasion of the intima by platelets and monocytemacrophages. After 72 and 168 hr, there was an increase and progression in preexisting modified smooth muscle cell plaques in which there developed prominent fibroplasia and collagenization. It is proposed that acute hypertension may be responsible for these changes. Such perinatal surges in blood pressure may be involved in the initiation of atherogenesis.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

The cytolytic activity of normal pregnancy serum was first studied on murine cancer cells and shown to be the result of a natural IgM antibody that binds to cell surfaces and activates complement. Both the classical and alternative pathways of complement are involved. It was then shown that certain human neuroblastoma cell lines, to the exclusion of other human cancers, react to the same system. It is proposed that this system may play a role in the cytolytic form of spontaneous regression of neuroblastoma.

Asunto(s)

RESUMEN

Cell lines from 26 human cancers were studied for cytotoxicity when treated with normal pregnancy serum. Cytotoxicity manifested by cell death and cytolysis, occurred in 4 of 8 neuroblastomas studied: SK-N-SH, NGP, LAN-5, and IMR-32. In NGP and SK-N-SH, evidence is presented showing that the cytotoxicity resulted from the cell-surface binding of a natural IgM 'antibody', which sensitized the neuroblastoma cells to the lytic action of complement (C). This system may be involved in a cytolytic form of spontaneous regression of neuroblastoma.

Asunto(s)

RESUMEN

An IgM fraction of human serum was isolated and purified. A portion of this fraction firmly attaches to L cells' surfaces, which sensitizes these cells to the lytic action of low concentrations of serum C. It contains the natural cytotoxic "antibody" to L cells.

Asunto(s)

RESUMEN

The natural cytotoxicity of human serum on murine L cells, EA and Sa 180 cells is expressed as a rapid cytolysis at 37 degrees C. This cytotoxic system is analyzed as to its active constituents and their functional relationships. Ultrastructural studies indicate that cell injury and death are initiated within 10 min by membrane disruption. A trypan blue assay for cell death was used to study serum toxicity in individual normal healthy adults, pregnant females and newborn infants. Pregnancy sera, particularly in the 2nd and 3rd trimesters, were consistently more toxic than male serum or nonpregnant females. Cord serum was typically nontoxic. Pools of normal fresh pregnancy serum were used for immunochemical analysis of the cytotoxic activity. By a variety of immunologic and immunochemical techniques it was shown that the cytotoxicity was, in part, due to the combined action of alternative and classical pathways of complement, the former being more prominent. The lytic action of complement was shown to be greatly amplified by the prior adsorption of IgM on the target cells' surface. This IgM is a critical determinant of the cytotoxic reaction. It probably contains a natural 'antibody' to cell surface antigen(s), whose combination activates both pathways of C.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Ultrastructural studies of blood cells during the acute stage of the hemolytic-uremic syndrome (HUS) revealed striking, but transient, changes in erythrocyte structure. These included membrane disruption, vacuolar degeneration, and Heinz body formation. There was also evidence of platelet injury, and there were peculiar tactile interactions between histiocytes and impaired red cells. These changes disappeared as the patients recovered. These changes were considered to be important in the pathogenesis of the hemolytic and thrombolytic features of HUS, and studies were directed at reproducing them in vitro and in vivo. Treatment of red cells with purified clostridial phospholipase C induced changes in red cells and platelets that were comparable to those encountered in HUS. Rats infused with phospholipase C developed hemolysis, thrombocytopenia, and hemoglobinuria. Their kidneys did not, however, reveal glomerular alterations similar to those seen in patients with HUS. It is proposed that HUS in some cases might be initiated by a nonspecific infectious injury to the intestinal mucosa thereby allowing increased absorption of toxins derived from indigenous gut flora and that these toxins could be responsible for the hemolysis, thrombolysis, and even the renal injury.

Asunto(s)

Asunto(s)

RESUMEN

Several basic empirical facts are emphasized about human developmental oncology. The first is that teratogenesis and oncogenesis are intimately related and that indeed teratogenesis may be the more primitive reaction to the types of mutagenic injury giving rise to neoplasm. The second is that neoplasms of early life, particularly those initiated "in utero" are rare, and tend to spontaneously regress or cytodifferentiate. The theoretical models of carcinogenesis forwarded by Knudson and Matsunaga are enlisted in attempts to explain these phenomena and how the oncogene is expressed and modulated by the fetal or embryonal milieu.

Asunto(s)

RESUMEN

The major genetic models of carcinogenesis are critically reviewed to determine their validity and relevance for clinical and experimental oncologists. Of major concern are the "two-hit" theory of Knudson and the host resistance system of Matsunaga. These models may be used to explain the pathobiologic peculiarities of human neoplasms, particularly those occurring in early life. It is proposed that certain benign and regressive tumors encountered in early life are expressions of the activity of the host resistance system.

Asunto(s)

Asunto(s)