The Last 5 Years of Basic Science Investigation in Transplant Immunology

Many new insights have been gained over the past 5 years into the mechanisms that regulate immune reactivity to cell and organ transplants. This new knowledge is being applied to the development of innovative experimental strategies that may soon be evaluated in the clinic.     

Alteration of the lipid composition of rat testicular plasma membranes by dietary (n-3) fatty acids changes the responsiveness of Leydig cells and testosterone synthesis

Experiments were conducted to assess whether changing dietary fat composition altered phospholipid composition of rat testicular plasma membranes in a manner that altered receptor-mediated action of luteinizing hormone (LH)/human chorionic gonadotropin (hCG). Weanling rats were fed diets that provided high or low cholesterol intakes and that were enriched with linseed oil, fish oil or beef tallow for 4 wk. Feeding diets high in (n-3) fatty acids decreased plasma and testicular plasma membrane 20:4(n-6) content. A marked reduction of the 22:5(n-6) content and an increase in the 22:6(n-3) content of testicular plasma membrane was found only in animals fed fish oil. A decrease in binding capacity of the gonadotropin (LH/hCG) receptor in the plasma membrane, with no change in receptor affinity, was observed for animals fed either linseed oil or fish oil diets. Dietary treatments that raised plasma membrane cholesterol content and the cholesterol to phospholipid ratio in the membrane were associated with increased binding capacity of the gonadotropin receptor. Feeding diets high in 18:3(n-3) vs. those high in fish oil altered receptor-mediated adenylate cyclase activity in a manner that depended on the level of dietary cholesterol. Feeding diets high in cholesterol or fish oil increased basal and LH-stimulated testosterone synthesis relative to that in animals fed the low cholesterol diet containing linseed oil. It is concluded that changing the fat composition of the diet alters the phospholipid composition of rat testicular plasma membranes and that this change in composition influences membrane-mediated unmasking of gonadotropin receptor-mediated action in testicular tissue.     

Absence of an association between HLA-DRB1*04 and rheumatoid arthritis in newly diagnosed cases from the community.

OBJECTIVES--To determine HLA-DR4 and DR1 allele frequencies in a series of patients with newly diagnosed early inflammatory arthritis. METHODS--HLA-DR1 and DR4 frequencies were determined by oligonucleotide typing of 208 patients classified as having either rheumatoid arthritis (RA) or undifferentiated inflammatory polyarthritis. RESULTS--The frequency of occurrence of DR4 in these patients with RA did not differ significantly from that in controls in the United Kingdom (42 v 37%). HLA-DR1 was increased in the group with inflammatory polyarthritis (25 v 18%). CONCLUSIONS--The frequency of DR4 is not increased in newly diagnosed community based patients with RA. This supports the hypothesis that DR4 is less important as a marker for susceptibility to RA than it is for disease persistence or severity.     

Three-Year Prospective Adherence to Three Breast Cancer Screening Modalities

Background.This study prospectively examined rates of adherence to mammography, clinical breast examination (CBE), and breast self-examination (BSE) in a cohort of women over 3 years to determine whether participation in BSE influenced participation in the other two screening modalities.Methods.Women ages 51 and older (n= 450) who attended a small group educational session to learn BSE and to hear about CBE and mammography guidelines were assessed annually by telephone for 3 consecutive years to determine their subsequent breast cancer screening behavior.Results.Annual CBE and mammography screening are highly positively associated. Regular performance of BSE has a modest positive association with both CBE and mammography adherence over time.Conclusions.Women who perform BSE regularly over time may be more likely to adhere to the other breast cancer screening guidelines.     

Bacterial meningitis in the first three months of life.

A retrospective study of infants with bacterial meningitis admitted to our hospital during 1949-52, highlighted the lack of ''classical'' signs of meningitis in these infants. We carried out a similar review of 44 infants aged less than three months, admitted during 1982-91. We also determined the causative organisms and their antibiotic sensitivities. Symptoms and signs were similar in the two series. Forty infants in the later series were either febrile, irritable or had seizures on the day of admission. Overall mortality fell from 30% to 11%. Between 1982 and 1991 Group B Streptocococcus and Neisseria meningitidis were the commonest causes of meningitis. All organisms, except one, were sensitive to ampicillin and/or cefotaxime. Bacterial meningitis should be suspected in young infants who are febrile, irritable or having seizures. Initial treatment with ampicillin and cefotaxime is appropriate.