Incidence of cardiac malformations in Greenlandic Eskimos

Summary 757 eskimo children born in Godthåb, Greenland, in the years 1957–1964 have been reexamined 1966. 10 certain and 4 probable cases of congenital heart disease were diagnosed, mostly cases of ventricular septal defect. The incidence of 1.3–1.9% is the highest registered in any ethnic group.The average mother's age of the patients was 32.1 years, the average mother's age of the total material was 26.8 years (0.01> P>0.001). The patients' average number in the sibship was 6.3, differing significantly (0.01> P>0.001). The patients' average number in the sibship was 6.3, differing significantly (0.01> P>0.001) from that of 3.2 in the total material. The social standard of the families of the patients was low.There is some indication that the incidence of cardiac malformations in the Greenlandic population is decreasing. This may be due either to improved social conditions or to a changing reproductive pattern with relatively fewer children born to old mothers.

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Zusammenfassung 757 Eskimokinder, die in Godthåb, Grönland, während der Jahre 1957–1964 geboren wurden, sind 1966 wieder untersucht worden. 10 sichere und 4 zweifelhafte Fälle von angeborenen Herzfehlern, insbesondere Fälle von Ventrikelseptumdefekt, wurden diagnostiziert. Die Incidenz von 1,3–1,9% ist die höchste, die in irgendeiner Bevölkerung registriert ist.Bei den Patienten war das durchschnittliche Alter der Mutter 32,1 Jahre gegen einen Durchschnitt im Gesamtmaterial von 26,8 Jahre (0,01> P>0,001). Die durchschnittliche Nummer der Patienten in der Geschwisterreihe ist 6,3, während die des Gesamtmaterials 3,2 ist (0,01> P>0,001). Die soziale Schicht der Patienten war insgemein sehr niedrig.Die Incidenz der angeborenen Herzfehler in der grönländischen Bevölkerung scheint abzunehmen. Dies mag eine Folge von besseren sozialen Verhältnissen sein, kann aber auch darin begründet sein, daß das reproduktive Muster der Grönländer sich geändert hat mit weniger Geburten bei älteren Müttern.

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Based on a paper read at the Second International Symposium on Circumpolar Health, June 1971, Oulu (Finland).     

Affinity maturation of a novel antagonistic human monoclonal antibody with a long VH CDR3 targeting the Class A GPCR formyl-peptide receptor 1

Therapeutic monoclonal antibodies targeting G-protein-coupled receptors (GPCRs) are desirable for intervention in a wide range of disease processes. The discovery of such antibodies is challenging due to a lack of stability of many GPCRs as purified proteins. We describe here the generation of Fpro0165, a human anti-formyl peptide receptor 1 (FPR1) antibody generated by variable domain engineering of an antibody derived by immunization of transgenic mice expressing human variable region genes. Antibody isolation and subsequent engineering of affinity, potency and species cross-reactivity using phage display were achieved using FPR1 expressed on HEK cells for immunization and selection, along with calcium release cellular assays for antibody screening. Fpro0165 shows full neutralization of formyl peptide-mediated activation of primary human neutrophils. A crystal structure of the Fpro0165 Fab shows a long, protruding V_H CDR3 of 24 amino acids and in silico docking with a homology model of FPR1 suggests that this long V_H CDR3 is critical to the predicted binding mode of the antibody. Antibody mutation studies identify the apex of the long V_H CDR3 as key to mediating the species cross-reactivity profile of the antibody. This study illustrates an approach for antibody discovery and affinity engineering to typically intractable membrane proteins such as GPCRs.