Murine IgG1 complexes trigger immune effector functions predominantly via Fc gamma RIII (CD16)

Previously, we have demonstrated that phagocytosis of IgG1-coated particles by macrophages in vitro is impaired by deletion of Fc gamma RIII in mice, suggesting that IgG1 may interact preferentially with Fc gamma RIII. In the present study, the biologic relevance of this observation was addressed by triggering various effector functions of the immune system in Fc gamma RIII(-/-) mice, using panels of mAbs of different IgG subclasses. Both binding and phagocytosis of IgG1-coated sheep or human erythrocytes by Fc gamma RIII(-/-) macrophages in vitro were strongly impaired, indicating that the impaired ingestion of complexed IgG1 by Fc gamma RIII(-/-) macrophages is due to a defect in binding. An in vivo consequence of the defective phagocytosis was observed by resistance of Fc gamma RIII-deficient mice to experimental autoimmune hemolytic anemia, as shown by a lack of IgG1-mediated erythrophagocytosis in vivo by liver macrophages. Furthermore, trapping of soluble IgG1-containing immune complexes by follicular dendritic cells in mesenteric lymph nodes from Fc gamma RIII(-/-) mice was abolished. Whole blood from Fc gamma RIII(-/-) mice was unable to induce lysis of tumor cells in the presence of IgG1 antitumor Abs. Finally, IgG1 mAbs proved unable to mount a passive cutaneous anaphylaxis in Fc gamma RIII(-/-) mice. Together, these results demonstrate that IgG1 complexes, either in particulate or in soluble form, trigger in vitro and in vivo immune effector functions in mice predominantly via Fc gamma RIII.     

Study on body mass index, lipid profile and lipid peroxidation status in coronary artery disease

Among the many known risk factors of coronary artery disease (CAD) obesity and hypercholesterolaemia are important ones. Whatever may be the risk factor, the basic pathology of CAD is deposition of altered lipids on the endothelium. One of such altered lipid is oxidatively modified low density lipoprotein (LDL). Lipid peroxidation has been assessed by several methods. Quantitation of malondialdehyde (MDA) by thiobarbituric acid (TBA) method is one of the commonly utilised method in several laboratories. In this study 40 cases of CAD were selected for evaluation. The body mass index (BMI), lipid profile and the level of lipid peroxidation (MDA) were measured. Seventeen cases (42.5%) had normal BMI (20-25), 20 cases (50%) were in the overweight range of BMI (26-30) and only 3 cases (7.5%) were in the obese group with a BMI more than 30. BMI correlated better with the level of total cholesterol (Tc), low density lipoprotein cholesterol (HDLc) and MDA. BMI did not show any correlation with triglyceride (Tg) or high density lipoprotein cholesterol (HDLc). MDA level correlated better with Tc, Tg levels and BMI, poorly correlated with LDLc and in inverse relationship was observed with HDLc.     

Psychosocial barriers to health promotion in an American Indian population

Northern Plains Indians (N = 200) completed the Indian Specific Health Risk Appraisal and measures assessing beliefs about risk factors and personal risk. Participants rated personal risk optimistically, judged their risk factor standing as superior to that of their peers, and neglected to consider risk factor standing when appraising personal risk. Moreover, participants were often not improving their standing on risk factors they considered relevant to their health. Such biases in health beliefs may prevent health interventions from being successful.     

On the future of the speciality of Obstetrics and Gynecology. A Dutch view

Between 4 and 15 ng/ml serum prostate-specific antigen (PSA) has a low specificity for prostate cancer (PCa). One accepted method to enhance this specificity is transrectal ultrasonography (TRUS)-measured PSA-density (PSA-D). We compared this method with a new alternative, transition zone PSA (PSA-TZ). We measured total and transition zone prostatic volumes by TRUS and calculated PSA-D and PSA-TZ in 59 patients with suspicion of PCa and PSA between 4 and 15 ng/ml. All patients then had sextant biopsies of the prostate, 30 were positive for PCa and 29 showed benign tissue. With a cut-off value of 0.35, PSA-TZ had a positive predicted value of 77% for PCa, whereas PSA-D, with a cut-off value of 0.12, had a positive predicted value of 55%. Our data suggest PSA-TZ to be more reliable for avoiding unnecessary biopsies in patients with PCa suspicion and serum PSA below 15 ng/ml. PSA-TZ, calculated by TRUS, enhances the specificity of PSA for needle biopsy diagnosis of PCa.     

Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: the Strong Heart Study

Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (> or = 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA1c, study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin.     

Immunohistochemical analysis of transferrin receptor: regional and cellular distribution in the hypotransferrinemic (hpx) mouse brain

The hypotransferrinemic (hpx) mouse mutant produces <1% of the normal circulating level of transferrin (Tf). Heterozygote animals of this strain (hpx/+) have approximately 50% of normal plasma Tf levels. In this study we examine the cellular and regional distribution of Tf receptor (Tf-R) in the brain of wild type, hpx/+ and mutant (hpx/hpx) mice. Also, using slot-blot (immunoblot) analysis, we describe the relative amount of Tf-R in brain microvessels of hpx/+ animals compared with wild type. Tf-R was seen primarily in neurons throughout the brains of wild type, hpx/+ and hpx/hpx animals. Gray matter areas immunoreacted more robustly than white matter areas. Oligodendrocytes and third ventricle tanycytes, both of which we have previously described as iron-positive, did not immunoreact for Tf-R. Tf-R immunohistochemical reaction in wild type, hpx/+ and hpx/hpx brains appeared similar. Immunoblot analysis of isolated cortical microvessels from wild type and hpx/+ animals revealed no upregulation of Tf-R expression in hpx/+ (relative to normal) despite a 50% decrease in circulating Tf levels. These results indicate that Tf-R is primarily expressed by neurons and that half normal levels of Tf (hpx/+) or transferrin supplementation (hpx/hpx) are apparently sufficient for normal expression and distribution of Tf-R. Because of the lack of circulating Tf, but unaltered Tf-R expression, hpx mice could serve as a model for delivery of therapeutic agents via the Tf/Tf-R system.     

Triploidy: antenatal sonographic features with post-mortem correlation

The CD34 antigen is expressed by human hematopoietic progenitor and stem cells. These cells are capable of reconstituting marrow function after marrow-ablative chemo-radiotherapy. Several different technologies have been developed for the separation of CD34+ cells from bone marrow or peripheral blood stem cell (PBSC) components. We used an immunomagnetic separation technique to enrich CD34+ cells from PBSC components in anticipation of autologous transplantation for patients with B lymphoid malignancies. Twenty-nine patients enrolled on this study and received mobilization chemotherapy followed by G-CSF. Of these, 21 achieved a peripheral blood CD34+ cell level of at least 2.0 x 10(4)/l required by protocol for separation of the stem cell components. A median of three components per patient was collected for processing. The average CD34+ cell concentration in the components after apheresis was 1.0 +/- 1.2%. After the CD34+ cell selection, the enriched components contained 0.6 +/- 0.6% of the starting nucleated cells. The recovery of CD34+ cells, however, averaged 58.4 +/- 19.2% of the starting cell number, with a purity of 90.8 +/- 6.5%. Overall depletion of CD34- cells was 99.96 +/- 0.06%. Nineteen patients were treated with marrow-ablative conditioning regimens and received an average of 6.2 +/- 2.0 x 10(6) CD34+ cells/kg body weight. These patients recovered to an ANC >0.5 x 10(9)/l at a median of 11 days (range 8-14), and platelet transfusion independence at a median of 9 days (range 5-13). Four patients died of transplant-related complications or relapse before 100 days after transplantation. No patient required infusion of unseparated cells because of failure of sustained bone marrow function. These data demonstrate that peripheral blood-derived CD34+ cells enriched by use of an immunomagnetic separation technique are capable of rapid engraftment after autologous transplantation.