Wing-Yen Wong

RENAL FAILURE IN SICKLE CELL ANEMIA

ESRD is a major complication in young adults with sickle cell anemia. As more patients with sickle cell anemia reach the third and fourth decades of life, the incidence of clinically apparent renal insufficiency will increase. As we understand the pathophysiology of renal damage and the effects of various therapies on the sickle renal vasculature, we can tailor specific management without further compromising already impaired renal function. Diagnostic clues must be recognized prior to the onset of irreversible damage, with appropriate intervention initiated at each age group. Bone marrow transplantation (BMT) is the only available cure for SCA at the present time. The demonstration that several distinct haplotypes of the beta s gene cluster on chromosome 11 influence the clinical expression of sickle cell anemia may be useful in delineating children who are at high risk for severe disease, and hence candidates for such hazardous therapeutic interventions as BMT prior to onset of clinically discernable disease. Current BMT preparative regimens can produce renal cortical and pulmonary toxicity, posing a patient selection problem in those cases in which the vasculopathy of the major organs is at an early stage and might be potentially repairable. Gene therapy without toxic preparative regimens is the ultimate answer. The challenge for the near future is the development of effective early therapeutic intervention during childhood and young adulthood.

Wounding acts as a tumor promoter in chickens inoculated with avian sarcoma virus 17

Avian sarcoma virus 17 (ASV17) is an acutely transforming retrovirus which carries the oncogene v-jun. The virus induces fibrosarcomas in chickens at the site of inoculation. Here we describe wound-related tumor formation in 77% of chickens inoculated with ASV17 in one wing and wounded by metal clip insertion in the opposite wing. Tumors from both wound-related and inoculation-related sites were histologically diagnosed as fibrosarcomas. Tissues cultured from both tumor sites produced infectious virus in culture and expressed high levels of the v-Jun oncoprotein detectable by immunofluorescent staining. By varying the time of wounding relative to virus inoculation we defined the early stages of wound healing (2-7 days postinoculation) as favoring wound-related tumor formation. Three other acutely transforming retroviruses containing oncogenes coding for nonreceptor protein tyrosine kinases (v-src, v-yes, and v-fps), inoculated in the same manner, induced wound-related tumors in all cases. We conclude that in chickens, ASV17 collaborates with wound healing to promote tumorigenesis by a process which may relate either to a biochemical function of Jun or to a more general, shared characteristic of transforming retroviruses.

Hematologic Profile and Lymphocyte Subpopulations in Hemoglobin SC disease: Comparison With Hemoglobin SS and Black Controls

Compared with subjects with homozygous SS disease (Hb SS), persons with hemoglobin SC (Hb SC) are known to have a more gradual loss of splenic function, a lower incidence of bacterial infections, and fewer end‐organ failures. We studied hematological indices and lymphocyte subpopulations of 27 Hb SC subjects and compared them with 173 Hb SS patients and 131 black controls. Hb SC patients had higher hemoglobin levels than Hb SS subjects, lower total leukocyte, granulocyte, monocyte, and lymphocyte counts. Platelets decresed with age but not significantly, instead of incressing as among Hb SS patients. Mononuclerar cells were generally similar to controls with the exception of CD8+HLA‐DR+ counts resembling Hb SS, Hematologic changes in Hb SC are limited to moderate granulocytosis in children and aduts, mild monocytosis in aduts, and increased activation of just one lymphocyte subset among those measured.