Acute respiratory distress syndrome in two rhesus macaques (Macaca mulatta).

Acute respiratory distress syndrome (ARDS) is an important and potentially life-threatening complication in humans that arises subsequent to a variety of primary insults including noxious fume inhalation, infection, and trauma. Here we describe the first two cases of ARDS reported in association with postoperative complications in rhesus macaques. In agreement with the multifactorial nature of the human syndrome, ARDS in one monkey was attributed to sepsis, whereas in the other it was ascribed to neurogenic trauma. Despite the different etiologies, both monkeys demonstrated clinical features of ARDS, including progressive dyspnea and pulmonary edema, and syndrome-defining histopathologic criteria including edema with intraalveolar neutrophils, fibrinohemorrhagic effusions with crescentic membranes, and interstitial vascular degeneration. Recognition and aggressive treatment of ARDS at an early stage may improve survival rates in dyspneic nonhuman primates with underlying extrapulmonary diseases.

Cosegregation of a factor VIII microsatellite marker with mild hemophilia A in Golden Retriever dogs.

Mild hemophilia A (factor VIII deficiency) was diagnosed in Golden Retrievers and pedigree studies were undertaken to test the cosegregation of an intragenic factor VIII marker with the disease phenotype. The study population consisted of 30 client-owned dogs (22 males and 8 females). Hemophilic males (n = 12) typically demonstrated prolonged bleeding after trauma or surgery rather than spontaneous hemorrhagic events. The affected males had a proportionate reduction in factor VIII coagulant activity (mean FVIII:C = 4%) and factor VIII protein concentration (mean FVIII:Ag = 3%). Twenty-five dogs (10 affected males, 8 clear males, 2 obligate carrier dams, and 5 suspect carrier daughters) were genotyped for a factor VIII microsatellite marker, with allele size assigned by an automated capillary electrophoresis system. Five distinct marker alleles were present in the study pedigree and a 300-base pair allele was found to segregate with the hemophilia A phenotype. The inheritance of the hemophilia-associated allele defined carrier status for 5 suspect daughters of obligate carrier dams. The limitations inherent to linkage analyses (i.e., lack of access to key family members and homozygosity at the marker locus) did not preclude carrier detection in this pedigree. We conclude that genotype analysis for the intragenic factor VIII marker can aid in control of canine hemophilia A through enhanced carrier detection.

Coimmunoprecipitation of UDP-glucuronosyltransferase isoforms and cytochrome P450 3A4.

Coimmunoprecipitation was used to investigate protein-protein interactions between several UDP-glucuronosyltransferase (UGT) isoforms and cytochrome P450 3A4. Solubilized human liver microsomes were incubated with specific antibodies to UGT2B7, UGT1A6, UGT1A1, and CYP3A4, and the immunoprecipitates were run on SDS-polyacrylamide gel electrophoresis. Western blots showed that UGT2B7, UGT1A6, UGT1A1, and CYP3A4 were successfully immunoprecipitated with the specific antibodies for each enzyme. Upon immunoprecipitating UGT2B7, the corresponding immunoblot showed that UGT1A6, UGT1A1, and CYP3A4 were immunoprecipitated. Similar studies found that different UGT isoforms or CYP3A4 immunoprecipitated along with the original immunoprecipitating enzyme. These data suggest that UGT isoforms may form complexes (dimers, tetramers, etc.) with each other in the endoplasmic reticulum and nuclear envelope. In addition, the UGT isoforms tested here may have interacted with CYP3A4 in the endoplasmic reticulum, suggesting that these enzymes may cooperate in the excretion of compounds in a multistep metabolic process.