Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer’s disease

Apolipoprotein-J/clusterin (APOJ/CLI) shares many biological properties with apolipoprotein-Ε (APOE) including, but not limited to, avid binding with β-amyloid peptide. Thus, APOJ/CLI warrants scrutiny as a candidate Alzheimer’s disease (AD) susceptibility gene. We identified seven nucleotide sequence polymorphisms in APOJ/ CLI, two of which, in exon 7, alter the predicted amino acid sequence. The JVIIB variant is an asparagine-to-histidine substitution, which deletes a glycosylation signal at amino acid 317; the JVIIC variant is an aspartate-to-asparagine substitution, which forms a new glycosylation signal at position 328. Both of these coding variants, as well as two neutral polymorphisms in exon 2, were more frequent in African-Americans than Hispanics and were rare in Caucasians. However, no individual coding or noncoding variant was consistently associated with AD. At the population level, APOJ/CLI polymorphisms are frequent among persons of African descent, but probably do not alter susceptibility to AD. Received: 14 February 1996 / Revised: 15 April 1996     

Fatal falciparum malaria in Canadian travellers

The authors report 2 cases of severe falciparum malaria in Canadians that had fatal outcomes. In the first case a man presented to a local hospital shortly after returning from Africa, but a diagnosis of malaria was not considered. He was transferred to a secondary and then to a tertiary care facility, where he subsequently died. Intravenous quinidine therapy, the treatment of choice, was unavailable at all 3 hospitals. In the second case, a woman taking chloroquine prophylaxis while visiting Nigeria developed cerebral malaria and died. These cases illustrate critical management issues: appropriate advice on malaria prevention before departure; consideration of malaria in all febrile people returning from an endemic area; ready access to parenteral therapy for severe malaria in Canadian hospitals; and an increase in awareness of travel medicine among family physicians.     

Accelerated Growth in Early Life and Obesity in Preschool Chilean Children

In Chile, childhood obesity rates are high. The purpose of this article is to compare BMI growth characteristics of normal (N), overweight (OW), and obese (OB) 5‐year olds from 0 to 5 years and explore the influence of some prenatal factors on these patterns of growth. The study was done on a retrospective cohort of 1,089 5‐year olds with birth weight >2,500 g. Weight and height were obtained from records at nine occasions (0–36 months); at 52 and 60 months, we measured them. At 60 months, children were classified as N, OW, and OB. At each age, BMI and z‐score of BMI (BMI Z) differences were compared among groups. The influence of birth weight, pre‐pregnancy BMI, and prenatal variables (weight gain, smoking, and presence of diabetes and preeclampsia) on BMI Z differences between N and OB was also explored. Adiposity rebound (AR) was not observed for the N, although for the OW, it occurred ～52 months and for the OB at ～24 months. BMI Z differences between N and OB were significant from birth, but were greatest between 6–12 and 36–52 months. Additional adjustment by birth weight, pre‐pregnancy BMI, and prenatal variables decreased the BMI Z differences for the first 24 months with virtually no effect after this age. Accelerated growth in OB children from post‐transition countries occurs immediately after birth, much earlier than the AR. The influence of prenatal factors on adiposity acquisition may extend at most until 2 years of life, although BMI gains thereafter are more related to postnatal variables.     

Potential use of tuftsin in treatment of candida peritonitis in a murine model

A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis caused by Candida albicans. Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection. Tuftsin was found to increase thioglycollate-elicited mouse peritoneal macrophage activity. 2x10(-7) M tuftsin enhanced two-fold cell association with radiolabelled candida, superoxide aniom production, and killing activity. Thus, a model consisting of mice undergoing peritoneal dialysis was developed in order to study the use of tuftsin as a therapeutic drug against peritoneal candidiasis. Administration of tuftsin (50 micrograms/mouse) before candidiasis induction with a lethal dose of candida (7x10(8) candida per mouse) improved mouse survival up to 70%, compared with 10% in the control group. The potential of tuftsin as a treatment for candidiasis was shown when the infection was induced with a sublethal dose of candida. Daily intraperitoneal injections of tuftsin (50 micrograms) to the sublethally infected mice caused a significant decrease in the number of candida recovered from the peritoneal cavity and from the blood (from 700 +/- 190 to 110 +/- 26 CFU/ml and from 100 +/- 26 CFU/ml to 17 +/- 8 CFU/ml, respectively). In addition, a larger number of peritoneal macrophages with greater phagocytic and killing activity were found in the tuftsin-treated mice. The effect of tuftsin may promote its potential use in the therapy of peritonitis in patients undergoing chronic peritoneal dialysis.