Management of phenylketonuria: South Australian experience of 13 cases

The management and present status of 13 children with phenylketonuria detected on the fifth day of life, who have been treated by diet thereafter for five to eight years, are discussed. In all 10 cases in which there has been continuous adequate dietary control of blood phenylalanine levels, the physical, social and mental development of the children has been normal. In some of these cases there is an unexplained discrepancy between the verbal and performance IQ scores. The present policy is to continue restricting the diet indefinitely, relaxation being permitted conditionally only after the age of seven years.     

Clinical evaluation of 99mTc-pyridoxylideneglutamate for hepatobiliary scanning

Clinical evaluation of hepatobiliary scanning using 99mTc-PG was done in twenty normal volunteers and eighty-three patients with liver and biliary tract disease. Satisfactory images of the biliary tract were obtained using small dosages of this agent. In normal humans, the agent reached the liver in 5 minutes, and the common bile duct, gallbladder, and duodenum in 10 to 20 minutes. The gallbladder was not visualized when the cystic duct was obstructed in patients with acute and chronic cholecystitis. In patients with partial common bile duct obstruction, a distended duct was visualized and there was delay in transit of radioactivity into the duodenum. With complete common bile duct obstruction, no radioactivity was seen in the biliary or gastrointestinal tracts up to 24 hours after injection. Hepatocellular disease was characterized by delayed liver clearance and delayed visualization of the biliary and gastrointestinal tracts. There were no toxic or other untoward effects in any patients.     

Helicobacter pylori generates superoxide radicals and modulates nitric oxide metabolism

During studies of the bactericidal action of nitric oxide (NO), we found that it reversibly inhibited the respiration of Escherichia coli and irreversibly inhibited the respiration of Helicobacter pylori. Peroxynitrite, a reaction product of NO and superoxide, irreversibly inhibited the respiration of both H. pylori and E. coli. H. pylori, but not E. coli, generated substantial amounts of superoxide radicals. These results suggest that NO directly inhibits the respiration of E. coli whereas it rapidly reacts with endogenously generated superoxide radicals in H. pylori. The resulting peroxynitrite inactivates the respiration of H. pylori.     

Thymic dendritic cells are primary targets for the oncogenic virus SL3-3

The murine retrovirus SL3-3 causes malignant transformation of thymocytes and thymic lymphoma in mice of the AKR and NFS strains when they are inoculated neonatally. The objective of the present study was to identify the primary target cells for the virus in the thymuses of these mice. Immunohistochemical studies of the thymus after neonatal inoculation of the SL3-3 virus showed that cells expressing the viral envelope glycoprotein (gp70(+) cells) were first seen at 2 weeks of age. These virus-expressing cells were found in the cortex and at the corticomedullary junction in both mouse strains. The gp70(+) cells had the morphology and immunophenotype of dendritic cells. They lacked macrophage-specific antigens. Cell separation studies showed that bright gp70(+) cells were detected in a fraction enriched for dendritic cells. At 3 weeks of age, macrophages also expressed gp70. At that time, both gp70(+) dendritic cells and macrophages were found at the corticomedullary junction and in foci in the thymic cortex. At no time during this 3-week period was the virus expressed in cortical and medullary epithelial cells or in thymic lymphoid cells. Infectious cell center assays indicated that cells expressing infectious virus were present in small numbers at 2 weeks after inoculation but increased at 5 weeks of age by several orders of magnitude, indicating virus spread to the thymic lymphoid cells. Thus, at 2 weeks after neonatal inoculation of SL3-3, thymic dendritic cells are the first cells to express the virus. At 3 weeks of age, macrophages also express the virus. In subsequent weeks, the virus spreads to the thymocytes. This pathway of virus expression in the thymus allows the inevitable provirus integration in a thymocyte that results in a clonal lymphoma.