Nesidioblastosis: the pathologic basis of persistent hyperinsulinemic hypoglycemia in infants. Morphologic and quantitative analysis of seven cases based on specific immunostaining and electron microscopy.

Seven surgical specimens of pancreas, obtained at laparotomy from infants suffering from persistent hyperinsulinemic hypoglycemia, were analyzed by qualitative and quantitative immunocytochemistry and by electron microscopy. In five cases a multifocal ductuloinsular proliferation, in one a focal adenomatosis, and in one a solitary encapsulated nodule (adenoma) were observed. Combinations of the different patterns of proliferation were seen in six cases. Budding off from the ductular epithelium and interposition of endocrine cells between ductular epithelial cells were prominent features common to all cases. An almost fivefold increase of the mean total area occupied by endocrine tissue was found over that of age-matched controls. Four cell types were seen to participate regularly in the proliferation, and their ratios were remarkably constant in all cases, mean figures being 62:21:9:8% for B:A:D:D1 cells, respectively. The ratio of B cells per total endocrine area in nesidioblastosis was very close to that per islet of the controls (62:59%). Since common features were found in all or in the majority of cases, it is suggested that the various patterns of proliferation are merely morphologic variations of the same basic defect. Nesidioblastosis may result from inappropriately controlled development of the endocrine pancreas that is not arrested but carries on beyond birth and during infancy. The application of specific immunocytochemistry as a necessity for full appreciation of the extent of endocrine proliferation is stressed.

Familial pheochromocytoma and islet cell tumor of the pancreas.

The occurrence of pheochromocytoma(s) or pancreatic islet cell tumor(s), or both, in two or more members of three unrelated families in a manner consistent with autosomal dominant inheritance suggests that this tumor association is a genetically determined syndrome. Among 11 affected patients (aged five to 53 years), 10 had pheochromocytoma (bilateral in six), four had islet cell tumor (multicentric in one), and three had both tumors. Clinical presentation was due to pheochromocytoma in 10 cases (symptoms or signs commencing before age 10 years in three patients) and islet cell carcinoma in one case. Four patients are dead as a result of the tumors--two from pheochromocytoma and two from islet cell carcinoma.

Effects of Triton-X-100 upon the mobility of esterases and alkaline phosphatases in disc electrophoresis.

Homogenates of the mid gut and digestive glands of Rhynchosciara angelae were prepared in 40% sucrose, with and without 0.5% Triton-X-100. These were subjected to disc electrophoresis and zymograms for esterases and alkaline phosphatase were prepared. In both groups the effect of Triton-X-100 was to increase the electrophoretic mobility of the enzymes concerned.

Diethylpyrocarbonate and benzoquinone vapour fixation for immunofluorescence studies of non-hormone protein in frozen dried tissues.

The use of gaseous (DEPC, BOV) postfixation of frozen-dried tissues for the fixation of non-hormone proteins was systematically studied. The fixation ability was tested on the "protein droplet model" i.e. the protein droplets formed in mouse liver after intravenous injection of bovine serum albumin (BSA). 1. There is no difference in the fixation ability for BSA between DEPC and BQV. 2. Both fixatives yield a very poor fixation of BSA in frozen-dried livers. In consequence, this protein is already extracted during section mounting and incubation for immunofluorescent tracing causing a strong substantial loss. 3. Remaining protein traces, however, are still immunoreactive indicating that DEPC and BQV fixation does not affect the antigenicity in considerable extent.

The cellular origin of motilin in the gastrointestinal tract.

The semithin-thin technique applied to serial resin-embedded sections, using sequential immunocytochemistry, conventional electron microscopy and silver staining, indicates that a population of enterochromaffin cells in the intestine contain, and therefore presumably synthesize and secrete, the 22-amino acid residue peptide motilin.

Differential localisation of substance P and motilin.

Motilin, and Substance P, have previously been shown to be present in enterochromaffin (EC) cells in the gut mucosa. By comparing a specific immunofluorescence stain for Substance P with an immunoperoxidase reaction for motilin, applied sequentially to the same tissue section, it is possible to demonstrate that the two peptides are present in different cells. It is concluded that a) at least two different types of EC cells must exist and b) these results provide further evidence for the neuroectodermal origin of the gastrointestinal APUD cells. Studies of the degranulation pattern of EC cells could help to elucidate the role of amines in the mechanism of storage and secretion of different peptides under normal and pathological conditions.