Hunter' syndrome. Ultrastructural features in young children.

Ultrastructural abnormalities in two stepbrothers with Hunter's syndrome, ages 1 and 4 years, were found in cortical neurons, neurons of the myenteric plexus, and skin. Inclusions containing little or no electron-dense material were noted in most tissues, and lamellar figures were restricted to cortical neurons and neurons of the myenteric plexus. These changes correlate with those described in tissues obtained at post mortem.

Gastrointestinal structure and function in Fabry's disease.

We evaluated gastrointestinal structure and function in 13 hemizygous males and 17 heterozygous females, five to 67 years old, from four kindreds with Fabry's disease. Gastrointestinal symptoms, noted in 62% (8/13) of the males and 29% (5/17) of the females, were present prior to the diagnosis of Fabry's disease in five patients; were discovered at the time of study in six patients and were associated with multiple other symptoms in two patients. Serum protein, albumin, folate, Vitamin B12, calcium, phosphorous, cholesterol and iron were normal in all 30 patients. Xylose absorption was normal in 2/2 males and 13/13 females studied. HLA B8 antigen was present in none of the males and 2/17 females. Peroral duodenal (one male), jejunal (six males, two females) and rectal (one male) biopsies on light microscopy demonstrated a normal villous pattern and luxol-fast blue positive "foamy" cell deposits in all males, while no deposits were visualized in the females. In all males and females studied, electron microscopic examination showed electron dense, intralysosomal "zebra-like" (0.5-0.75 micrometer.) bodies in the vascular endothelial and perithelial cells and in the cytoplasm of the small unmyelinated neurons, and perineurial cells. Despite the frequency of gastrointestinal symptoms, both malabsorption and celiac disease were absent.

Ulcerative eosinophilic granuloma of the tongue. A light- and electron-microscopic study.

Ulcerative eosinophilic granuloma of the tongue simulates histiocytosis X or cancerous lesions, and may be subjected to unnecessary excessive treatment. This case report illustrates its benign, self-limited nature, discussed the differential diagnosis, and postulates its pathogenesis on the basis of light- and electron-microscopic findings.

Subcutaneous and skeletal chordomoid nodules in an infant.

Multicentric subcutaneous and skeletal nodules with histologic features of chordoma developed over a period of 3 months in a black infant. Radiolucent intracranial lesions were demonstrated by pneumoencephalogram and computerized tomography scan. The patient received chemotherapy and the nodules regressed. After a follow-up of 7 years, there has been no recurrence of these chordomoid lesions and the child enjoys good health and normal growth and development. In retrospect, these nodules appear to be a benign, self-limited heterotopias and not malignancies. The cells with physaliphorous characteristics may represent unusual differentiation of fibroblasts rather than indicating notochordal origin.

Thyroid carcinoma following treatment for acute lymphoblastic leukemia.

A 2 1/2-year-old girl with acute lymphoblastic leukemia received chemotherapy and prophylactic cranial irradiation. After six years of remission, including three years off therapy, metastatic thyroid carcinoma appeared in the cervical lymph nodes. The predisposing factors for the development of thyroid carcinoma as a second malignancy in this case are discussed. It is suggested that thyroid carcinoma should be added to the growing list of second malignancies in acute lymphoblastic leukemia and that careful thyroid examination be included in the follow-up of long-term survivors.

Direct cloning of human neuroblastoma cells in soft agar culture.

An in vitro soft agar technique was used in an attempt to culture neuroblastoma cells from 71 bone marrow, 3 lymph node, and 2 solid tumor specimens from 18 patients with neuroblastoma. One-half of each specimen was sent for routine pathology studies and one-half was cultured in the soft agar system. Colonies appeared within 10 days in histologically positive bone marrows. Light microscopy, electron microscopy, catecholamine secretion, and karyology provided evidence that the colonies were composed of neuroblastoma cells. There were 38 instances in which histological study of the specimen demonstrated neuroblastoma cells. The soft agar system showed colony growth in 30 of these samples (79%). There were a total of 38 specimens that were histologically negative for neuroblastoma. Thirty of these 38 specimens showed no growth in the stem cell assay. Eight histologically negative specimens from 6 patients formed colonies in the soft agar system. Five of these 6 patients showed tumor histologically on prior or subsequent marrow examinations. In addition to a significant correlation between histological and soft agar culture results (p < 0.001), there exists a highly significant positive correlation between the number of colonies per plate and the histological status of the specimen (p < 0.005). Serial marrow samples were cultured on 7 patients. There appears to be an association between the number of colonies that develop in the plate and the clinical course and prognosis of the patient. Decreasing plating efficiencies (number of colonies per number of cells plated) correlated with tumor response. Increasing plating efficiencies indicated tumor relapse. A plating efficiency of greater than or equal to 0.1% portended a particularly poor prognosis. Neuroblastoma grows well in this soft agar culture system. This excellent growth provides a good model for both clinical and basic science studies of neuroblastoma.

Characteristics of an acid active thiamine diphosphatase from beef brain.

That thiamine has a role in nerve conduction as well as synaptic transmission is suggested by the following observations. (1) Thiamine phosphate esters are hydrolyzed and released from nerve membranes during nerve conduction. (2) Ultraviolet radiation of single nerve fibers at the wavelength specific for thiamine destroys the ability of that nerve to conduct an impulse. (3) Thiamine diphosphatase (TDPase) is present on synaptosomes. Previous articles have characterized an alkaline active TDPase in brain; this report characterizes a PH 5 active TDPase and compares it properties to the pH 9 enzyme. Both enzymes require a divalent cation for optimal activity. The pH 5 enzyme is more sensitive to ATP. Myelin fractions of brain have the highest specific activity for the acid TDPase, and the nerve ending particles the highest total activity. No PO4 3-inhibition was observed. Kinetic constants of this enzyme activity are reported.

Immunological block to synthetic alpha-melanocyte-stimulating hormone: melanocyte interaction by antibodies isolated from cell-column immunoadsorbents.

Antibodies to formalin-fixed, syngeneic melanoma cells were prepared in mice, purified by immunoaffinity chromatography, and tested for binding activity to viable melanoma cells. The radiolabeled antibodies detected congruent to 9 X 10(6) melanoma antigenic sites/cell. The calculated average association constant (Ka) for the antibody population was 7 to 10 X 10(7) M-1. The antibody was shown to block the binding of melanocyte-stimulating hormone in competitive cell surface binding studies. Results are discussed conceptually in terms of the potentially important role that the humoral immune response may play in the phenomenon of tumor progression.

Desacetyl vinblastine amide sulfate induced ineffective erythropoiesis.

Ineffective erythropoiesis occurred during desacetyl vinblastine amide sulfate (VDS) therapy of a patient with metastatic Ewing's sarcoma. The peripheral blood was characterized by anisocytosis, poikilocytosis and reticulocytopenia. Bone marrow showed megaloblastic red cell hyperplasia with nuclear fragmentation, binuclearity and abnormal metaphases. Radioiron incorporation into red cells was markedly decreased. Electron microscopy showed red cell surface changes previously called ropalocytosis. Normal erythropoiesis promptly resumed when VDS treatment was withheld. Although less common than leukopenia, red cell abnormalities are part of the spectrum of vinca alkaloid toxicity.

JC Papovavirus in progressive multifocal leukoencephalopathy.

Brain tissue from seven patients with progressive multifocal leukoencephalopathy was tested for the presence of papovaviruses. JC virus, ahuman papovavirus, was identified in all seven cases. Virus was isolated in tissue culture from extracts from each of four patients and was detected by immunofluorescence in sections from the other three. The new osolates were indistinguishable from the prototypical JC strain serologically and in all biological characteristics examined. Thus JC virus has, to date, been associated with 20 cases of progressive multifocal leukoencephalopathy.

The role of beta-adrenergic activity in the production of cardiac and aortic arch anomalies in chick embryos.

The sympathomimetic amines isoproterenol, epinephrine, norepinephrine, and phenylephrine are structural derivatives of beta-phenylethylamine and have proportionately different effects on alpha- and beta-adrenergic receptors. Chick embryos in ovo were each administered a single dose of one of these compounds at concentrations ranging from 0.4 times 10(-9) to 20 times 10(-9) mol/5 mul saline during Hamburger and Hamilton stages 20-27. In other experiments embryos were pretreated with the beta-antagonist propranolol and subsequently administered isoproterenol. 743 cardiovascular anomalies were produced. The production of cardiovascular anomalies was proportional to the degree of beta-adrenergic activity of each drug. The frequency of anomalies was significantly reduced by pretreatment with propranolol. At all concentrations tested the anomaly rate was greater in chick embryos receiving an experimental compound than in controls. The general types of anomalies included aortic arch defects, ventricular septal defect, double outlet right ventricle, aortic hypoplasia, and truncus arteriosus. These results demonstrate that activation of the beta-adrenergic receptor mechanism is directly related to the cardiovascular anomalies produced in the chick embryos.