Biomed. & Phnrmucorher., 43 (1989) 145-147 0 Elsevier, Paris
GENETICS Hereditary angioedema Hereditary angioneurotic edema is a disease resulting from quantitative or functional defects of the plasma protein C!-Inhibitor, which controls several proteases involved in crucial steps of the complement, the coagulation and the tibrinolytic system. Although the autosomal dominant mode of transmission of the disease was established as early as 1917, it was not clear until recently whether the genetic defect affects the structural Cl-Inhibitor gene or a distinct regulatory loctts. The isolation of complementary DNA probes for human Cl-Inhibitor has now made it possible to examine directly the structural Cl-Inhibitor locus in patients and in normal individuals. After digestion of the leukocyte DNA with restriction endonucleases, DNA fragments were separated electrophoretically and transferred to a membrane (Southern blot) for molecular hybridization with complementary DNA probes. The results of such family studies demonstrated that the disease cosegregates with deletions of a portion of the structural gene detectable in certain families affected by the quantitative form of the Cl-Inhibitor defect (type I, or common form of hereditary angioedema). Early diagnosis is thus possible, at the DNA level, in families carrying detectable DNA alterations. A more detailed knowledge, at the molecular level of the normal and other abnormal Cl-Inhibitor genes will guide the design of improved DNA probes for a more general diagnosis of the disorder. M. Tosi (1) Institut Pasteur, 75724 Paris Cedex 15, France
findings in 31 patients show that the presence of a tumor stem line with near-normal DNA content predicts a favorable outcome of therapy, whereas the lack of this feature almost always means the child will relapse. We recommend that patients whose tumors lack stem lines with near-normal DNA content be considered candidates for alternative treatment. A.T. Look (2) St Jude Children’s Research Hospital, Memphis, Tennessee 38101 0318, USA
OBSTETRICS Cigarette smoking and pregnnncy The association between cigarette smoking during pregnancy and fetal hypoxia and fetal growth retardation is well-known, whereas the association between smoking and perinatal mortality is disputed. By using data from the Swedish Medical Birth Registry, cigarette smoking as a risk factor for late fetal and early neonatal death was studied. From 1983 to 1985 more than 280.000 births were reported to the registry, which included practically all Swedish births. The overall rates of late fetal and early neonatal deaths were 3.5 and 3.1 per 1000 respectively. About 30 per cent of the women were recorded as daily smokers. Smoking increased the risk foremost for late fetal death (relative risk = 1.4), but also for early neonatal mortality (relative risk= 1.2). It was concluded that in countries like Sweden, smoking may be the most important preventable risk factor for late fetal death. S. Cnattingius (3) Uppsala University, 75185 Uppsala, Sweden
ONCOLOGY Neardiploid tumor stem lines in patients with osteosarcoma From one-half to two-thirds of children with apparently localized osteosarcoma, a rapidly spreading tumor of bone, respond well to amputation followed by intensive chemotherapy and can look forward to permanent cure. The remainder experience a return of their disease in the lungs and eventually die despite efforts to induce new responses. We suspected that it might be possible to identify these potentially poor responders by studying the cellular DNA content (chromosome number) of osteosarcoma cells at diagnosis, using flow cytometry. Our (1) N. Engl. J. Med. (1987) 317, I.
Congenital toxoplasmosis When infection with Toxoplasma Gondii occurs during pregnancy, there is a risk that the parasite will cause severe congenital toxoplasmosis. We developed a method of diagnosing and treating congenital toxoplasmosis in utero. Diagnosis was based on the identification of maternal acute infection, followed by culture of fetal blood and amniotic fluid, testing of fetal blood for toxoplasma specific IgM and nonspecific measures of infection, and ultrasound examination of
(2) N. Engl. J. Med. (1988) 318, 1567. (3) Br. Med. J. (1988) 297. 258.