Interrupted aortic arch type B1 in a brother and sister: suggestion of a recessive gene.

We report on the occurrence of an identical form of interrupted aortic arch and ventricular septal defect in a brother and sister whose parents are not consanguineous. The first child died on the 7th day of life without surgery 3 years ago; the second underwent surgical correction on the 5th day of life and is doing well.

Hypothalamic-pituitary-gonadal function in two infants with Smith-Lemli-Opitz syndrome.

We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20-desmolase deficiency, 17 alpha-hydroxylase deficiency, and 3 beta-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5 alpha-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies.

Macrophage cytotoxicity towards isolated rat islet cells: neither lysis nor its protection by nicotinamide are beta-cell specific.

In animal models of Type 1 (insulin-dependent) diabetes mellitus macrophages were shown to be the first immunocytes that infiltrate the pancreatic Langerhans islets in the autoimmune process. We now show direct macrophage cytotoxicity against isolated rat islet cells in an electron microscopical study, which permits investigation of the specificity of this process. Freshly isolated islet cells were co-incubated with syngeneic peritoneal macrophages at a target: effector-cell ratio of 1:2. After various time periods, the cells were directly fixed and embedded; the ratio of live and dead cells was evaluated by electron microscopy. Our results demonstrate that activated but not resident macrophages lyse islet cells in a time-dependent manner. After 15 h of co-incubation lysis of islet cells is complete. No islet cell-macrophage contacts and no differences between the lysis of Beta cells or non-Beta cells were observed during the observation period. Islet cells encapsulated in alginate were also lysed by macrophages as a direct proof for soluble mediator(s) of cytotoxicity. Nicotinamide protected islet cells from lysis in a dose-dependent manner. As a result of this electron microscopic study we conclude that even at very low target: effector ratios, activated macrophages lyse syngeneic islet cells regardless of islet cell type via secretion of humoral mediator(s).

Spontaneous cytotoxicity of macrophages against pancreatic islet cells.

Activated peritoneal macrophages were found to lyse syngeneic [3H]leucine-labeled pancreatic islet cells or rat insulinoma cells after 15 h of coculture at 37 degrees C. Lysis was verified by electron microscopic analysis. Islet cell lysis was dependent on the T:E ratio and was comparable with P815 and L929 tumor cells used as targets. The cytotoxic activity was localized in the adherent fraction of Corynebacterium parvum activated peritoneal cells and was destroyed by incubation of cells with macrophage-toxic silica particles. Syngeneic thyrocytes and hepatocytes were found to be resistant to the cytolytic action of activated macrophages. It has been shown previously that macrophages contribute to pancreatic islet inflammation. The present in vitro analysis demonstrates that macrophages can function as effector cells in islet destruction.

Truncus arteriosus communis associated with interrupted aortic arch: a report on two uncommon cases.

The paper presents two infants with the A-4 type of truncus arteriosus communis (according to Van Praagh's classification). One patient who survived a surgical procedure demonstrated a rare variant of aortic arch interruption to the left off the left subclavian artery (type A according to Celoria and Patton), whereas the second presented an uncommon anomaly in which the right subclavian artery originated from the descending aorta with associated severe truncal valve incompetency. The authors describe the clinical picture along with the surgical treatment of the first infant who being six days old was subjected to a correction employing the wide patent ductus arteriosus to reconstruct the aortic arch, following the method described by Gomes and McGoon. Subsequently an aortic homograft was implanted in order to connect the right ventricle and the pulmonary artery.

Essential contribution of macrophages to islet cell destruction in vivo and in vitro.

A number of observations indicate an essential role of macrophage activity in the development of hyperglycemia in animal models of Type I diabetes. Administration of macrophage-toxic silica particles prevents spontaneous diabetes development in BB rats or NOD mice. The same result was noted in the low-dose streptozotocin-induced diabetes model in mice. Macrophages appear to be the first immune cells infiltrating islets during early insulitis. Macrophages in inflamed islets of BB rats bear the ED1 marker, whereas resident islet macrophages are ED2-positive. In vitro, ED1-positive macrophages were found to lyse pancreatic islet cells to a similar degree to various tumor cells but not normal thyrocytes. Macrophage-mediated lysis of islet cells was inhibited in the presence of 10-100 mM nicotinamide.