Characterization of the high-affinity cell-surface receptor for murine B-cell-stimulating factor 1

Radiolabeled recombinant murine B-cell-stimulatory factor 1 (BSF-1) was used to characterize receptors specific for this lymphokine on the surface of primary B and T cells and in vitro cell lines representing the B-cell, T-cell, mast cell, macrophage, and myelomonocytic lineages. BSF-1 binding was rapid and saturable at 4 degrees C and 37 degrees C with a slow dissociation rate. On all cell types examined, BSF-1 bound to a single class of high-affinity receptor (less than 2000 receptors per cell) with a Ka of 10(10)-10(11) M-1. Receptor expression on resting primary B and T cells was low (less than 100 receptors per cell), whereas activation with lipopolysaccharide or Con A produced a 5- to 10-fold increase in receptor numbers. Among a panel of lymphokines and growth hormones, only unlabeled BSF-1 was able to compete for the binding of 125I-labeled BSF-1. Affinity crosslinking experiments resulted in the identification on all cells tested of a receptor protein with an average Mr of 75,000.     

Hb Ullevaal [β78(EF2)Leu→Val; HBB: c.235C>G], a New Hemoglobin Variant Interfering with Hb A1c Measurement Using a Cation Exchange High Performance Liquid Chromatography Method

A new hemoglobin (Hb) variant was detected during Hb A_1c measurement. DNA sequencing showed heterozygosity for the single nucleotide substitution (C?>?G) on the β-globin gene causing an amino acid change [β78(EF2)Leu→Val; HBB: c.235C?>?G]. The new Hb variant was designated Hb Ullevaal after the hospital at which it was discovered. Heterozygosity for Hb Ullevaal appears to have no clinical significance. However, it interferes with Hb A_1c measurement by cation exchange high performance liquid chromatography (HPLC), causing falsely low Hb A_1c concentration when using the Tosoh G7 apparatus in variant mode.     

Monday and non-Monday concentrations of lifestyle-related blood components in the Oslo Diet and Exercise Study

Urdal P, Anderssen SA, Holme I, Hjermann I, Mundal HH, Haaland A, Torjesen P (Ullevål University Hospital; Norwegian University of Sport and Physical Education; and Aker University Hospital, Oslo, Norway). Monday and non-Monday concentrations of lifestyle-related blood components in the Oslo Diet and Exercise Study. J Intern Med 1998; 244 : 507–13. Objective We hypothesized that participants of intervention studies have an unfavourable lifestyle at the weekend compared with the rest of the week, thus affecting the concentrations of components in samples drawn on Mondays. Design The hypothesis was examined using data from the Oslo Diet and Exercise Study, a 2 × 2 randomized intervention trial on diet and exercise involving 209 participants. Each person chose which day of the week to attend for blood sampling, both before and after the 1 year of intervention. Main outcome measures Comparison of mean concentrations of the components measured, in samples drawn on Mondays vs. non-Mondays, both at the start and at the end of intervention. Results At the start, nine components, from haemostasis, carbohydrate and lipid metabolism, showed a difference of more than 10% between Monday and non-Monday values, all Monday values differing from the non-Monday values in a cardiovascularly unfavourable direction. Participants starting and ending on a Monday showed the unfavourable profile both times, and those who were examined both times on a non-Monday showed a consistently favourable profile, whereas those who changed the day of examination at the start and end changed profile accordingly. Conclusion The lifestyle-related components examined here showed differences between Monday and non-Monday values, which were not due to a selection bias. We suggest they may be related to a different lifestyle at the weekend compared with ordinary working days. If such effects are not recognized and properly taken into account, they may markedly affect the outcome of intervention studies.     

Reference intervals for eight enzymes in blood of adult females and males measured in accordance with the International Federation of Clinical Chemistry reference system at 37°C: part of the Nordic Reference Interval Project

As part of the Nordic Reference Interval Project we present reference intervals for alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), lactate dehydrogenase (LD), alkaline phosphatase (ALP), gamma‐glutamyltransferase (GT), amylase (AMY) and pancreatic type of AMY in blood of adult males and females. A total of 3036 reference persons, all of whom considered themselves to be in good health, were recruited by 102 Nordic clinical biochemical laboratories. Exclusions were undertaken on the basis of predefined biochemical and clinical criteria. Enzyme activities in serum and plasma were measured in the different laboratories using various commercially available routine measurement systems at 37°C. Only results obtained with the International Federation of Clinical Chemistry (IFCC) compatible measuring systems were selected for estimation of the enzyme reference intervals. The final number of results on each enzyme varied from 459 (LD) to 2300 (ALT). The 2.5 and 97.5 percentile reference limits were calculated by a non‐parametric method in accordance with the IFCC recommendations, using the Refval 4.0 data program. Statistical partitioning testing was undertaken to decide whether the reference intervals ought to be partitioned according to gender and/or age. For most of the enzymes, but not for all, the upper reference limits were found to be higher than those that have been in general use until now.     

Additional value of red blood cell parameters in predicting uncommon α-thalassemia; experience from 10 years of α-globin gene sequencing and copy number variation analysis

Introduction

The diagnosis of rare forms of α-thalassemia requires laborious genetic analyses. Accurate sample selection for such evaluation is therefore essential. The main objectives of this study were to investigate the predictive power of red blood cell parameters to detect rare forms of α-thalassemia (substudy 1), and to explore the frequency of rare versus common forms of α-thalassemia in our sample population (substudy 2).

Methods

In substudy 1, we reviewed all blood samples selected for extended α-hemoglobinopathy evaluation at our laboratory during 2011–2020 (n = 1217), which included DNA sequencing and/or copy number variation analysis. We assessed α-thalassemia positive samples at different levels of mean corpuscular hemoglobin (MCH) alone and in combination with results for red blood cell count (RBC) or red cell distribution width (RDW). In substudy 2, we examined the distribution of α-thalassemia genotypes for all samples submitted to a first-tier hemoglobinopathy evaluation at our laboratory during 2014–2020 (n = 6495).

Results

In substudy 1, both RBC and RDW added predictive value in detecting rare forms of α-thalassemia in samples from adults and children. In adult samples with MCH ≤ 23 pg, the presence of erythrocytosis increased the detection rate from 27% to 74% as compared to non-erythrocytosis, while normal RDW increased the detection rate from 36% to 86% as compared to elevated RDW. In substudy 2, rare forms of α-thalassemia were detected in 12% of α-thalassemia positive samples.

Conclusion

Initial assessment of MCH, RBC, and RDW provided valuable predictive information about the presence of rare forms of α-thalassemia during hemoglobinopathy evaluation.     

Macroamylase immunoglobulins show high affinity for animal and human amylases

We have examined the affinity shown by the immunoglobulin fraction from each of five sera containing macroamylase for amylases from different sources: human saliva or human, porcine, or ovine pancreas. High affinity constants, 0.4 X 10(10) to 7.2 X 10(10) L/mol, were found in competitive binding experiments with human or porcine pancreatic amylase. All but one serum yielded linear Scatchard plots, indicating that in most sera the amylase-binding immunoglobulins are homogeneous, possibly monoclonal. The immunoglobulin fractions from different sera differed in their specificity: two of them bound all four types of amylases, whereas two bound only one type. Three of the five immunoglobulin fractions showed considerably higher affinity towards one or both of the animal amylases than towards the human ones, and may be primarily directed against some animal amylase.     

Macro creatine kinase BB isoenzyme in serum: most likely an antigen-autoantibody complex

Nine sera containing an abnormal creatine kinase BB isoenzyme, "macro CK-BB", were examined. Immunoglobulin precipitation after addition of radiolabelled CK-BB suggested that in eight of the sera the enzyme was linked to an immunoglobulin G. Results obtained with papain-digested and with pepsin-digested IgG suggested that the binding of CK-BB occurred in the antigen-binding region (the "Fab-region") of IgG. Each of the two antigen-binding fragments of IgG, obtained by papain-digestion, were CK-BB specific, since they complexed this isoenzyme equally well when excess CK-MM and CK-MB was added. From Scatchard plots the affinity constant for binding of CK-BB to IgG and the BB-binding capacity of four of the sera was calculated. The affinity constant was high and differed little between the sera (range 0.7 x 10(11)-1.6 x 10(11)1/mol). The BB-binding capacity differed widely (range 21-900 microgram of CK-BB per litre of serum), but in each serum it roughly paralleled the activity of the macro CK-BB complex. The results suggest that in eight of the nine sera examined the BB-binding IgG is an antibody with activity directed towards CK-BB.     

Combined diet and exercise intervention reverses the metabolic syndrome in middle-aged males: results from the Oslo Diet and Exercise Study

We examined the single and combined effects of a 1-year diet and exercise intervention on the International Diabetes Federation (IDF) metabolic syndrome among middle-aged males. The study was a randomized, controlled, 2 x 2 factorial intervention study. Participants included 137 men with metabolic syndrome according to the IDF criteria aged 40-49 years randomly allocated to four intervention groups: diet alone (n=34), exercise alone (n=34), the combination of the diet and exercise intervention (n=43) or control (n=26). The main outcome measure was metabolic syndrome as defined by IDF criteria (2005). In the combined diet and exercise group, 14 participants (32.6%) (P<0.0001 as compared with control) had the metabolic syndrome after 1-year intervention. In the diet-only group, 22 participants (64.7%) (P=0.023 vs control) and in the exercise-only group 26 participants (76.5%) (P=0.23 vs control) had the metabolic syndrome following the intervention. Utilizing the factorial design, both dietary and exercise intervention had significant effects (P<0.005) on the resolution of the metabolic syndrome. Both exercise and dietary intervention reduced metabolic syndrome prevalence compared with control after 1 year of intervention. However, the combined diet and exercise intervention was significantly more effective than diet or exercise alone in the treatment of the metabolic syndrome.