ABSTRACT
Defects in a triad of organelles (melanosomes, platelet granules, and lysosomes) result in albinism, prolonged bleeding, and lysosome abnormalities in Hermansky-Pudlak syndrome (HPS). Defects in HPS1, a protein of unknown function, and in components of the AP-3 complex cause some, but not all, cases of HPS in humans. There have been 15 inherited models of HPS described in the mouse, underscoring its marked genetic heterogeneity. Here we characterize a new spontaneous mutation in the mouse, cappuccino (cno), that maps to mouse chromosome 5 in a region conserved with human 4p15-p16. Melanosomes of cno/cno mice are immature and dramatically decreased in number in the eye and skin, resulting in severe oculocutaneous albinism. Platelet dense body contents (adenosine triphosphate, serotonin) are markedly deficient, leading to defective aggregation and prolonged bleeding. Lysosomal enzyme concentrations are significantly elevated in the kidney and liver. Genetic, immunofluorescence microscopy, and lysosomal protein trafficking studies indicate that the AP-3 complex is intact in cno/cno mice. It was concluded that the cappuccino gene encodes a product involved in an AP-3-independent mechanism critical to the biogenesis of lysosome-related organelles. (Blood. 2000;96:4227-4235)
Subject(s)
Disease Models, Animal , Hermanski-Pudlak Syndrome/genetics , Membrane Proteins/genetics , Mice, Mutant Strains/genetics , Monomeric Clathrin Assembly Proteins , Adaptor Protein Complex alpha Subunits , Adaptor Proteins, Vesicular Transport , Adenosine Diphosphate/blood , Animals , Blood Platelets/chemistry , Blood Platelets/pathology , Chromosome Mapping , Eye/pathology , Genes , Genes, Recessive , Genetic Heterogeneity , Hair Color/genetics , Hermanski-Pudlak Syndrome/epidemiology , Hermanski-Pudlak Syndrome/pathology , Humans , Kidney/enzymology , Kidney/ultrastructure , Lipofuscin/metabolism , Liver/enzymology , Liver/ultrastructure , Lysosomes/enzymology , Melanosomes/pathology , Mice , Mice, Inbred C3H , Models, Animal , Phenotype , Puerto Rico/epidemiology , Serotonin/blood , Skin/pathology , Species SpecificityABSTRACT
BACKGROUND: Considerable skepticism still exists about the role of diagnostic laparoscopy in the evaluation of penetrating abdominal trauma. The reported experience with therapeutic laparoscopy has been limited. METHODS: Retrospective analysis of a collective experience from three large urban trauma centers with 510 patients (316 stab wounds, 194 gunshot wounds) who were hemodynamically stable and had no urgent indications for celiotomy. RESULTS: Laparotomy was avoided in 277 of the 510 patients (54.3%) either because of nonpenetration or insignificant findings on laparoscopy. All were discharged uneventfully after a mean hospital stay of 1.7 days. Twenty-six had successful therapeutic procedures on laparoscopy (diaphragmatic repair in 16 patients, cholecystectomy in 1 patient, hepatic repair in 6 patients, and closure of gastrotomy in 3 patients) with uneventful recovery. In the remaining 203 patients, laparotomy was therapeutic in 155. Fifty-two patients had nontherapeutic celiotomy for exclusion of bowel injuries or as mandatory laparotomy for penetrating gunshot wounds (19.7%). The overall incidence of nontherapeutic laparotomy was 10.2%. Complications from laparoscopy were minimal (10 of 510) and minor. CONCLUSIONS: Laparoscopy has an important diagnostic role in stable patients with penetrating abdominal trauma. In carefully selected patients, therapeutic laparoscopy is practical, feasible, and offers all the advantages of minimally invasive surgery.