The acute phase response of adult rats is altered by in utero exposure to maternal low protein diets.

The immune system has been previously demonstrated to be under the influence of maternal nutrition in pregnancy. Assessment was made of the effects of low protein diets (12, 9 and 6 g casein/100 g diet) fed before conception and during pregnancy on the immune system of the resulting offspring in early adulthood. Control animals were fed a diet containing 18 g casein/100 g. At the end of pregnancy all dams were fed a nonpurified diet containing 18.3 g protein/100 g. Male pups were weaned onto this diet, which they consumed until the age of 7 wk. Rats exposed to 18 g casein/100 g diet in utero mounted a typical acute phase response following E. coli endotoxin challenge at age 7 wk. Food intake was 75% lower, hepatic zinc concentrations 25% greater, and serum albumin 15% lower than in saline-injected controls. Pulmonary glutathione levels were 35% greater in endotoxin-treated rats than in saline-treated controls. In rats exposed to low protein diets in utero the trend was for the acute phase response to be blunted. This was most noticeable with respect to the anorectic response, hepatic zinc uptake and pulmonary glutathione uptake. In rats not challenged with endotoxin, maternal diet had pronounced effects on tissue zinc status at the age of 7 wk. Liver zinc concentrations were 21% and 16% lower in the groups exposed to 9 and 6 g casein/100 g diets relative to the control group exposed to 18 g casein/100 g diet. Glutathione status was altered in all groups exposed to low dietary protein in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of haemoglobin level in sickle cell-haemoglobin C disease.

The determinants of steady state haemoglobin levels in sickle cell-haemoglobin C (SC) disease were investigated by measuring routine haematological and biochemical indices, red cell survival, oxygen affinity, pitted erythrocytes, and red cell and plasma volumes in 31 adult patients (15 male; 16 female). Red cell survival was shortened in all subjects, and was positively correlated with haemoglobin level. However, many haemoglobin values were within the normal range, especially in male subjects. Palpable splenomegaly, which occured in 53% of patients, did not appear to affect haemoglobin level, red cell survival, plasma volume, or red cell volume, but was associated with lower platelet counts and decreased pitted red cells. Sex related differences were found in total haemoglobin, packed cell volume, conductivity cell volume, red cell count, and in the blood volume measurements. Red cell, plasma and total blood volumes in patients varied with weight and cube of height in manner observed in normal subjects, although red cell volumes were lower and plasma volumes were greater than in normal subjects of given height and weight. Anaemia in SC disease is related to the haemolytic rate but the major determinant appears to be an inappropriate increase in plasma volume.

Beta-chain variants in Jamaican newborns.

In an electrophoretic study of 15,661 Jamaican cord bloods, 8 rare beta-chain variants were found in 18 subjects in addition to the common beta-chain variants, Hb S and Hb C. The heterozygote frequencies for Hb S and Hb C were 10.1% and 3.7% respectively. The most frequent of the rare beta-chain variants were Hb Korle Bu (beta 73 Asp leads to Asn) (7 cases) and Hb O su-Christiansborg (beta 52 Asp leads to Asn) (3 cases). One new beta-chain variant, Hb Caribbean (beta 91 Leu leads to Arg) was found.

Beta-thalassaemia of clinical significance in adult Jamaican Negroes.

Over a 9-year period, three adult Negro patients with beta-thalassaemia of clinical significance were recognized out of approximately 185 000 new adult patients attending the University Hospital. These patients, aged 15-58 years, have clinical and haematological characteristics within the spectrum of beta-thalassaemia intermedia; which in this paper refers to phenotypes resulting from defects in beta-chain synthesis clinically intermediate between classical Cooley's anaemia and beta-thalassaemia trait, genetic classification being dependent on family study. Family studies established the presence of two beta-thalassaemia genes conclusively in one case (proposita, family A); presumptively in another (propositus, family C); while in the remaining subject (proposita, family B), who has two similarly affected siblings, homozygosity is suspected, but not proven by family study. In simultaneous 59Fe and 51 Cr studies, estimates of effective erythropoiesis are in reasonable agreement with measurements of red cell destruction.

Erythrocyte Hb-S concentration. An important factor in the low oxygen affinity of blood in sickle cell anemia.

The blood in sickle cell anemia has a very low oxygen affinity and, although 2,3-diphosphoglycerate (2,3-DPG) is increased, there is doubt as to whether this is the only factor responsible. In this study of 15 patients with sickle cell anemia (Hb SS) no correlation was found between oxygen affinity (P(50) at pH 7.13) and 2,3-DPG in fresh venous blood. Whole populations of Hb SS erythrocytes were therefore separated, by an ultracentrifuge technique, into fractions of varying density. The packed red cell column was divided into three fractions; a bottom fraction rich in deformed cells or irreversibly sickled cells (ISC), with a very high mean corpuscular hemoglobin concentration (MCHC); a middle fraction containing cells with the highest content of fetal hemoglobin; and a top fraction containing reticulocytes and discoid cells but free of deformed cells. Oxygen affinity was shifted to the right in all layers (mean P(50) (pH 7.13)+/-1SD: top 46.3+/-2.9 mm Hg: middle 49.8+/-4.9 mm Hg; bottom 61.0+/-5.8 mm Hg) compared with normal blood (top 32.1+/-0.7 mm Hg: bottom 30.1+/-0.5 mm Hg). 2.3-DPG was increased in the top fraction, but was low or normal in the bottom fraction (top 21.8+/-3.4 mumol/g Hb: middle 17.7+/-2.2 mumol/g Hb; bottom 13.8+/-3.1 mumol/g Hb; normal whole blood 14.3+/-1.2 mumol/g Hb). The level of 2,3-DPG in top fractions could not account for the degree of right shift of P(50), and in the middle and bottom fractions the even greater right shifts were associated with lower levels of 2,3-DPG. Top fraction cells depleted of 2,3-DPG had a higher, but still abnormally low, oxygen affinity. A strong relationship was found between oxygen affinity and MCHC. The fractions with the greatest right shift in P(50) had the highest MCHC (top 32.4+/-2.0; middle 36.2+/-3.1; bottom 44.6+/-3.2 g/100 ml, respectively) and the plot of P(50) vs. MCHC showed a positive correlation (r = 0.90, P < 0.001). The red cell population in sickle cell anemia is not homogeneous but contains cells of widely varying Hb F content, 2,3-DPG, and hemoglobin concentration. Paradoxically, the cells with the lowest O(2) affinity have the lowest 2,3-DPG, but they also have the highest concentration of Hb S. The dense, deformed cell called the ISC is but the end stage in a process of membrane loss and consequent increase in hemoglobin concentration. The P(50) of Hb SS blood is, to a large extent, determined by the presence of these cells (r = 0.85, P < 0.001). Increased concentration of Hb S in the cell favors deoxygenation and crystallization even at relatively high P(o2). Lowered affinity for oxygen appears to be closely associated with Hb S concentration and not with 2,3-DPG content.