Alfredo Pinto

Expression of markers shared between human natural killer cells and neuroblastoma lines

SummaryNeuroblastoma is a tumor of neuroectodermal origin arising most commonly from the adrenal medulla. We have examined the ability of several monoclonal antibodies which recognize markers predominantly expressed on human natural killer (NK) cells to react with neuroblastoma cell lines in vivo derived sections of tumor. HNK-1 (Leu 7) is a monoclonal IgM antibody which recognizes a carbohydrate epitope on NK cells and a wide range of tumor cell types. We have shown that HNK-1 recognizes the human neuroblastoma lines SMS-KCNR, SMS-KAN, NMB/N7, and IMR/5. Expression of this antigen on cell lines can be slightly increased by retinoic acid-induced differentiation of the cells. N901 (NKH1), a monoclonal antibody raised against interleukin 2-dependent human NK cell lines also recognizes all human neuroblastoma cell lines examined. This expression is independent of differentiation induction and levels remain unaltered following retinoic acid treatment of the cell lines. Lastly, with monoclonal antibody 49H.8, it has been found that reactivity of the lines is weak until induction of differentiation, after which highly significant increases of reactivity are seen. 49H.8 recognizes several cryptic carbohydrate antigens with varying affinities, shown to identify mouse and rat NK cells. In contrast to other NK markers, human neuroblastoma cell lines did not express significant reactivity with B73.1, Leu 11b, or Leu 18. Immunohistochemical staining of sections of human neuroblastoma tumors correlated with the in vitro findings; however, staining with N901 and 49H.8 was only seen on frozen sections, not paraffin-embedded. The significance of shared NK cell-neuroblastoma/neuron antigens is currently under investigation.

Trisomy 21 and isodicentric chromosome 21 in Kostmann syndrome following treatment with G-CSF

A child with Kostmann syndrome, or severe congenital neutropenia, developed myelodysplastic syndrome after 6 years of treatment with rhG-CSF. The bone marrow karyotype showed acquired trisomy 21, and in some cells pentasomy 21 due to two isodicentric chromosomes 21. This is the second report of a patient with Kostmann syndrome and acquired trisomy 21.

Mitochondrial abnormalities of liver in two children with citrullinaemia.

Citrullinaemia is a rare inborn error of urea-cycle metabolism. Two affected children are reported in whom progressive metabolic instability suggested the possibility of hepatopathy or an ongoing hepatic mitochondrial injury. A percutaneous liver biopsy was performed in each patient. Electron-microscopic findings were similar in both cases. Approximately 20% of the mitochondria were abnormally enlarged with paracrystalline inclusions and electron-dense bodies of different sizes and shapes present in the matrix. The specificity of these findings is discussed in the context of previous reports of ultrastructural abnormalities in the hepatocytes of patients with inborn errors of the urea cycle. It is speculated that the mitochondrial abnormalities in citrullinaemia may be related to the accumulation of citrulline in the mitochondria which may eventually manifest as metabolic instability.

Immune complex disease consistent with systemic lupus erythematosus in a patient with lysinuric protein intolerance

Lysinuric protein intolerance (LPI) is an autosomal recessive metabolic disease caused by defective transport of cationic amino acids on the basolateral :membrane of epithelial cells and the plasma membrane of parenchymal cells. The transport defect is expressed in the intestinal enterocyte, kidney tubules, hepatocytes and skin fibroblasts (Perheentupa and Visakorpi 1965; Rajantie et al 1980a,b,c, 1981; Smith et al 1987; Simell 1995). Urinary excretion of lysine, arginine and ornithine is increased while intestinal absorption is decreased. Patients with LPI have a marked tendency to develop acute progressive respiratory insufficiency as well as haematological and renal complications (Rajantie et al 1981). The acute respiratory insufficiency is more common in children and has been associated with pulmonary haemorrhage and/or alveolar proteinosis (DiRocco et al 1993; Parto et al 1993; Kerem et al 1993). An immunological basis for these life-threatening complications has been suggested in one patient (Nagata et al 1987), but generally the immunological responses in LPI are not defined. In this case study, we present evidence that immune complex disease may be more common than previously thought in patients with LPI.

Argininosuccinic aciduria: Long-term treatment with arginine

The presentation and 2 year treatment of a patient with argininosuccinic aciduria is reported. Erythrocyte argininosuccinate lyase activity was less than 2% of normal. Long-term management included protein restriction and arginine dietary supplementation. The child experienced three episodes of hyperammonaemia (>100 µm), the first at birth, the second at 6.5 months and the third at 16 months. Neurological development deteriorated between 14 and 24 months. Hepatomegaly and biochemical hepatitis, a feature of this condition, was accompanied by enlarged mitochondria with tubular paracrystalline inclusions not previously recognized in this disorder.

A Shared Founder Mutation Underlies Restrictive Dermopathy in Old Colony (Dutch-German) Mennonite and Hutterite Patients in North America

A Shared Founder Mutation Underlies Restrictive Dermopathy in Old Colony (Dutch-German) Mennonite and Hutterite Patients in North America Catrina Loucks, Jillian S. Parboosingh, Jessica X. Chong, Carole Ober, Victoria M. Siu, Robert A. Hegele, C. Anthony Rupar, D. Ross McLeod, Alfredo Pinto, Albert E. Chudley, and A. Micheil Innes* Department of Medical Genetics, Alberta Children’s Hospital and Alberta Children’s Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada Department of Human Genetics, The University of Chicago, Chicago, Illinois Department of Obstetrics and Gynecology, The University of Chicago, Chicago, Illinois Department of Paediatrics and Biochemistry, University of Western Ontario, London, Ontario, Canada Departments of Biochemistry and Medicine, Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada Department of Pathology and Lab Medicine, University of Calgary, Calgary, Alberta, Canada Program in Genetic and Metabolism, Children’s Hospital, Department of Pediatrics and Child Health and Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada

Hyperdiploid karyotype in a choroid plexus papilloma

A choroid plexus papilloma from a 23-month-old child was found to have a hyperdiploid karyotype. This karyotype is compared with that of other choroid plexus papillomas. Our results are also compared with flow cytometry results and the karyotypes of choroid plexus carcinomas.

Mesenchymal hamartoma of the liver with inversion of chromosome 19.

A mesenchymal hamartoma of the liver (MHL) from a 20-month-old girl was studied cytogenetically. The karyotype was 46,XX,inv(19)(p13q13.4)[38], and fluorescence in situ hybridization using bacterial artificial chromosome probes refined the breakpoints to 19p13.11 and the subtelomeric region of 19q. This is the first report of inversion (19) in MHL, and the q-arm breakpoint is different from that reported previously in other rearrangements.

Recurrent respiratory papillomatosis causing chronic stridor and delayed speech in an 18-month-old boy

Recurrent respiratory papillomatosis is a relatively uncommon disease that presents clinically with symptoms ranging from hoarseness to severe dyspnea. Human papilloma virus types 6 and 11 are important in the etiology of papillomas and are most probably transmitted from mother to child during birth. Although spontaneous remission is frequent, pulmonary spread and/or malignant transformation resulting in death has been reported. CO2 laser evaporation of papillomas and adjuvant drug therapy using lymphoblastoid interferon-alpha are the most common treatments. However, several other treatments have been tried, with varying success. In the present report, a case of laryngeal papillomatosis presenting with chronic stridor and delayed speech is described.