Neurocristopathy: its growth and development in 20 years.

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.

The development of preatherosclerotic coronary artery lesions in perinatal piglets.

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).

The effects of acute norepinephrine-induced hypertension on the coronary arteries of newborn piglets.

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.

Spontaneous regression of neuroblastoma: an experimental approach.

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.

The cytolysis of human neuroblastoma cells by a natural IgM 'antibody'-complement system in pregnancy serum.

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).

Isolation of a natural cytotoxic IgM "antibody" in human serum sensitizing L cells to complement.

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.

Natural cytotoxicity of human serum. A natural IgM 'antibody' sensitizes transformed murine cells to the lytic action of complement.

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.

Experimental studies on the hemolytic-uremic syndrome.

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.

Models and concepts derived from human teratogenesis and oncogenesis in early life.

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.

Genetic models of carcinogenesis.

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.

Thymic involution mimicking thymic dysplasia: a consequence of transfusion-induced graft versus host disease in a premature infant.

A premature infant with ostensibly normal immunologic function received two exchange blood transfusions for hyperbilirubinemia and several blood and platelet transfusions for pancytopenia. A fatal graft vs host reaction (GvHR) ensued that was diagnosed by skin biopsy one day prior to death at age 40 days. Autopsy revealed characteristic alterations of GvHR in the spleen, lymph nodes, gut, and liver.

Thymic stromal alterations in mice undergoing a chronic graft-versus-host reaction.

Graft-versus-host induced immunosuppression has previously been shown to be accompanied by severe morphological changes in the thymus; furthermore chronic GvH could become acute by grafting a normal syngeneic thymus, suggesting a functional defect in the autologous thymus. In this work, we monitored the changes occuring in two biologically active thymic stromal fractions during a state of chronic GvH reaction. It was thus observed that a soluble thymic factor (STF), normally found in the reticuloepithelial cells, was lost, and that an insoluble thymic fraction (ITF) found in a double basement membrane surrounding medullary blood vessels, became markedly hypertrophied.