C3 Deposition in IgA Nephropathy in Children and Adolescents

The aim of this study was to assess the significance of C3 deposition in IgA nephropathy in children and adolescents. One hundred and two patients aged 5–21 years (57 male and 45 female) were studied. The findings of C3 deposition were classified into 8 groups by immunofluorescent (IF) pattern and intensity as follows: group MC3+ (N = 12): mesangiocapillary pattern and 3+ in intensity; group MC2+ (N = 13): mesangiocapillary and 2+; group MC1 + (N = 4): mesangiocapillary and 1 +; group M3+ (N = 11): mesangial and 3+; group M2+ (N = 24): mesangial and 2+; group M1 + (N=18): mesangial 1 +; group S (N = 12): only segmentally positive; and group N (N = 8): negative. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration, and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, fibrous crescents, adhesion and tubulo-interstitial change). IF findings were scored semiquantitatively and laboratory findings were also studied. The following results were obtained: 1) The scores of total activity index in MC groups were higher than in the M, S or N groups, and the greater the degree of C3 deposition, the higher the score; 2) Such result was not evident in the chronicity index; 3) High IF scores of IgG and IgM were found in the MC3+ and MC2+ groups; 4) Hematuria was more severe in MC3+ and MC2+ than in other groups, and proteinuria was more prominent in the MC than other groups. Thus the degree of C3 deposition was parallel with histological activity and urinary findings.     

Nutritional Anemias

Prevention of nutritional deficiencies should be attained by the consumption of a good diet. Unfortunately, in the case of iron, this is not always possible, and it is advantageous to fortify food with iron. Milk-based formulas and cereals are the most commonly used iron-fortified products in infancy and early childhood. Bioavailability of iron from cereals is low and more clinical studies on the field are necessary to demonstrate the effectiveness of iron-fortified cereals in infants and children of developing countries. Infections and excessive blood loss in infancy related to the use of fresh, pasteurized or powdered cow milk result in much of the anemia we currently see in industrialized countries. Vitamin A deficiency interacts with iron metabolism and recent intervention studies have shown that anemia in Vitamin A deficient children can be successfully treated with oral supplements.     

Pattern of renal dysfunction in analgesic nephropathy--comparison with glomerulonephritis.

Comprehensive renal function tests were performed in 84 patients with analgesic nephropathy, 33 glomerulonephritis patients matched for creatinine clearance, and 30 control subjects. A system of 1-day renal function tests including urine microscopy, creatinine clearance, phenolsulphonphthalein excretion, urine concentration and acidification, and electrolyte excretion, was used. Patients with analgesic nephropathy were found to have significant sterile pyuria and haematuria, even those with mild renal insufficiency, significantly reduced concentrating ability and a distal acidifying defect, and a tendency to impaired sodium conservation. These function defects are consistent with the primary lesion of renal papillary necrosis in analgesic nephropathy; the detection of these defects have implications in patient management.     

Usefulness of antiendomysial antibodies as a serological marker in coeliac children

The new diagnostic criteria of coeliac disease (CD) give more importance to serological markers. Immunoglobulin A antiendomysial antibodies (IgA-EmA) were determined in 138 sera from 79 coeliac children and the antibody levels compared to IgG and IgA antigliadin antibodies (IgG-AGA, IgA-AGA) in the sera. The assessment was also carried out in 29 children with other gastrointestinal diseases, 29 with non-gastrointestinal diseases and 35 healthy children. The IgA-EmA had a 91.4% specificity and a 88.4% sensitivity for active CD. The corresponding figures were 89.8% and 64.4% for IgA-AGA and 73.7% and 86.2% for IgG-AGA, respectively. The results of IgA-EmA determinations were concordant with the intestinal biopsy findings in 90% of cases, versus 80% for IgA-AGA and 83% for IgG-AGA. In most of the discordant cases the biopsy showed only minor changes, making the classification difficult. All patients with positive IgA₂-EmA also had positive IgA₁ EmA antibodies. IgA-EmA are an excellent serological marker of CD activity in children and they are useful to decrease the number of intestinal biopsies which are needed to confirm the diagnosis in coeliac patients.     

High-grade T-cell lymphoma following treatment with cyclosporin A

A 47-year-old man with persistent severe oropharyngeal ulceration developed a high-grade T-cell lymphoma soon after commencing treatment with cyclosporin A. Using Southern blotting to identify T-cell beta-chain gene rearrangements, evidence of clonal restriction was found both in blood and lymph node DNA samples. Two BamH1 rearranged bands were demonstrated in both samples. In the blood a 16 Kb band predominated, with a weaker 28 kb band. In the lymph node sample this pattern was reversed. The findings suggest that a bi-clonal population of T-lymphocytes or clonal evolution of an existing T-cell monoclone had developed, and that cyclosporin contributed to the emergence of a high-grade T-cell lymphoma.     

Immunoglobulin Y Levels in Egg Yolk From Three Chicken Genotypes

Laying hens are very efficient producers of antibodies and provide an interesting alternative for large-scale production of specific antibodies. These antibodies also have biochemical advantages over mammalian antibodies (e.g. rabbit antibodies) that can be used to improve immunoassays where antibodies are used. The concentration of IgY in egg yolk is an important production parameter. The purpose of this study was to investigate the genetic variation of IgY levels in egg yolk. We have compared IgY concentrations in egg yolks from two lines, selected for egg production traits at the Swedish University for Agricultural Sciences (Single Comb White Leghorn and Rhode Island Red) and a cross between the two lines (SLU-1392). Single Comb White Leghorns have the highest mean concentration of yolk IgY, 2.21 mg ml^-1 compared to SLU-1392 1.95 mg ml^-1 and Rhode Island Red 1.68 mg ml^-1. The cross thus had an intermediate IgY concentration in relation two the two other lines. There were great differences between individual animals within each line. Our results indicate that it should be possible to increase yolk antibody production by using a high producing chicken line and by genetic selection within the line. We found three individuals with very low yolk IgY concentrations among the Rhode Island Red hens. Newly hatched chickens with limited amounts of IgY from the hen may be more susceptible to infections.     

Ultrastructural localization of blood group antigen A in normal and neoplastic urothelium

The subcellular distribution of the blood group antigen A in the transitional epithelium of the urinary tract and its neoplastic growths was studied using transmission immuno-electronmicroscopy. Sixty-five tissue specimens from 50 blood group A1 patients were processed according to an immunogold procedure which was optimized for preservation of both antigen and ultrastructure. The reactions were stronger in the glycocalyx of the luminal surfaces and at the interdigitating cytoplasmic processes of the cells. In the intracellular compartment the reactions were associated with tubulovesicular membrane-bound structures and with the Golgi complexes. Secretory products, intra- or extra-cellular, were also positive. The greatest variability was noted in the cell surface reactions, which were positive in 88% of normal but only 41% of neoplastic urothelial specimens. An inverse correlation was found between malignant behaviour and cell surface, but not intracellular, reactions. We conclude that, in transitional cell carcinomas, there is a quantitative defect in the processing of substance A which affects predominantly the cell surface component and may involve either the transport-insertion steps, the plasma membrane-associated glycosyltransferases or internalization of blood group antigen A.     

PLASMA PHOSPHOLIPASE A2 ACTIVITY IN CLINICAL ACUTE MYOCARDIAL INFARCTION

1. Phospholipase A2 (PLA2) cleaves phospholipids to produce a lyso-phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2 may play a role in many disease states. Lyso-phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme. 2. Plasma PLA2 activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid from Escherichia coli cell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2-4, and days 6-9. Normal age matched males (n = 13) were also studied. 3. Plasma PLA2 in patients with uncomplicated myocardial infarction (n = 12) was, initially, 1.14 +/- 0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 +/- 0.14). On days 2-4, PLA2 activity increased to 1.94 +/- 0.18 (P less than 0.001) and this activity was correlated with the earlier peak CK level (P less than 0.02). On days 6-9, PLA2 activity was 1.49 +/- 0.13 while in two patients who developed complications and underwent open-heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL. 4. The increase in plasma PLA2 in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysiology is uncertain.     

Expression of the cell surface antigen detected by the monoclonal antibody A7 in pancreatic carcinoma cell lines

In a previous study, we used a murine monoclonal antibody, A7, against human colon carcinoma as a drug-carrier to treat colorectal cancer.¹ In the present study, we found that MAb A7 also reacted immunohistochemically with 73% of human pancreatic carcinoma cell lines, with the A7 antigen mainly being detected on the cell surface. However, the A7 antigen was found in only 9% of the spent media of these human pancreatic carcinoma cell lines by ELISA. On the other hand, the positive incidence of CA19-9, POA, ferritin, CEA, DU-PAN-2 and SLX in those spent media was 100%, 64%, 64%, 55%, 55% and 36%, respectively. These results suggest that the A7 antigen may only rarely be shed into the sera of pancreatic cancer patients, in which case MAb A7 could be a suitable drug-carrier in targeting chemotherapy for pancreatic cancer patients.     

Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.