Studies on antigenic relatedness of classic and variant strains of infectious bursal disease viruses

Antigenic relatedness of six classic and variant strains of serotype 1 infectious bursal disease virus (IBDV) and one serotype 2 IBDV was investigated by Western blotting and enzyme-linked immunosorbent assay (ELISA) using polyclonal, monoclonal, and monospecific antibodies to single viral proteins (VP2 and VP3). All virus strains cross-reacted similarly, and the viruses were not distinguishable from each other by ELISA or Western blot analysis performed with polyclonal or non-neutralizing monoclonal and monospecific antibodies. Non-neutralizing antibodies against the VP2 (40 kilodaltons) reacted strongly with VP2 of classic and variant strains of serotype 1 and reacted weakly with VP2 of serotype 2 OH strain. This indicated that common antigens were recognized and that these epitopes were not strictly dependent on the native structure of the virus.     

Lipoprotein lipase, LDL receptors and apo-lipoproteins in human fetal membranes at term

Ultrastructurally, all cells of human fetal membranes strongly exhibit a large amount of lipid deposits throughout pregnancy. Their origin and function is still unknown. The aim of this study was to investigate the localization of key components of lipid metabolism in this tissue. Using immunohistochemical techniques, the distribution of lipoprotein lipase (LPL), low density lipoprotein receptors (LDL receptors), and apo-lipoprotein B and E was investigated in 20 human fetal membranes at term. In addition, electron microscopy was used to study the intracellular localization of lipoprotein-sized particles. Amnionic epithelium and trophoblast cells reacted strongly for LPL. LDL receptors and apo-lipoproteins were present in amnionic epithelium and fibroblasts of the amnion. In none of the investigated cells were lipoprotein-sized particles identified. Similar results were obtained in all 20 cases. The findings indicate that lipoprotein from the amniotic fluid or from the maternal circulation may serve as substrate for lipids in human fetal membranes.     

Biological effects of the dihydroorotate dehydrogenase inhibitor polyporic acid, a toxic constituent of the mushroom Hapalopilus rutilans, in rats and humans

Inhibitors of dihydroorotate dehydrogenase (DHO-DH), such as brequinar or leflunomide, have been intensively tested for their antitumour and immunomodulating effects. Polyporic acid (PA) from the mushroom Hapalopilus rutilans (H. r.) also is a DHO-DH inhibitor (50% inhibitory concn., IC50, 10(-4)-10(-3) M). As three people had been poisoned following ingestion of H. r. we wanted to investigate the effects of PA in rats and in cell cultures. Rats given PA via probang (100-800 mg/ kg) within 24 h developed strongly reduced locomotor activity, depressed visual placing response and impaired wire manoeuvre. Laboratory investigation of blood revealed hepatorenal failure, metabolic acidosis as well as hypokalaemia and hypocalcaemia. All symptoms closely paralleled the effects seen in the poisoned people. Proliferation of cultured cells (including rat brain neurons and glia, fibroblasts, tumour cells) was depressed at 10(-4)-10(-3) M PA. We conclude that the intoxication of people poisoned with H. r. is due to the high content of the DHO-DH inhibitor PA.     

EblacZ tumor dormancy in bone marrow and lymph nodes: active control of proliferating tumor cells by CD8+ immune T cells

A well-defined lacZ gene tagged DBA/2 lymphoma (EblacZ) was used to examine the role of host immune responses in controlling tumor dissemination and persistence, as well as metastasis. In s.c. and intra-ear pinna-inoculated mice, low numbers of EblacZ cells homed to the bone marrow and lymph nodes. The frequency of bone marrow-residing tumor cells did not change with the growth of primary tumor or with multiple inoculations of tumor cells. The bone marrow-residing tumor cells expressed the proliferation-associated Ki67 antigen and expanded upon CD8+ depletion. In contrast, inoculation of nu/nu or severe combined immunodeficiency mice or of immune-suppressed DBA/2 mice led to the rapid outgrowth of EblacZ cells in the bone marrow and their metastasis to other organs. Transfer of bone marrow from EblacZ immunized MHC congenic or syngeneic DBA/2 donors, but not from naive donors, protected s.c.-inoculated DBA/2 mice. Protection was abrogated by in vitro depletion of CD8+ T cells prior to transfer of bone marrow. These experiments show that bone marrow and lymph nodes are privileged sites where potentially lethal tumor cells are controlled in a dormant state by the immune system. Metastasis may be a consequence of the breakdown of this immune control.     

Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Hvid?re Study Group on Childhood Diabetes

Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross-sectional, non-population-based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4-6.3%, mean 5.4%). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 +/- 1.3% (mean +/- SD) compared with 8.9 +/- 1.8% in those aged 12-18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg(-1) 24 h(-1)) in children aged 2-9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37% (n = 1071) used three or more. Of those on two or three injections daily, 37% used pre-mixed insulins, either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on pre-mixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbA1c was related to use of more short-acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few.     

The effects of cooling systems on CO2-lased human enamel

The thermal effects on dentin during CO2 laser irradiation on human enamel were investigated. To simulate the clinical practice, two cooling methods (air and water spray) were applied immediately after laser exposure, whereas one group without cooling was served as control. Three hundred and sixty uniform tooth blocks were obtained from freshly extracted human third molars. Temperature change measurements were made via electrical thermocouple implanted within the tooth block 2 mm away from the enamel surface. Experimental treatments consisted of lasing without cooling, lasing with 0.5-ml/sec water cooling, and lasing with 15-psi air cooling. Our results indicated that (1) both air- and water-cooling groups could reduce temperature elevation significantly; (2) the larger power energy resulted in the higher temperature elevation. In conclusion, for CO2 laser irradiation on human enamel both water- and air-cooling methods may be effective on prevention of thermal damage of pulp.     

Electrocardiographic patterns relative to initiating mechanisms of exercise-induced ventricular tachycardia

The initiating mechanisms of exercise-induced ventricular tachycardia were studied in a population of 5842 patients who performed 9064 bicycle exercise tests. Sixty (1%) patients had 194 episodes of ventricular tachycardia during the test. Forty-two percent of these occurred during exercise and 58% during recovery. Two different initiating electrocardiographic patterns were observed. In 17 (28%) patients ventricular tachycardia was initiated by a short-long-short sequence of R-R intervals (group 1). Thirty-eight (63%) patients did not have this pattern of interval changes preceding ventricular tachycardia (group 2). Five (8%) other patients showed both patterns. The clinical characteristics of the groups were different for angina and cardiomyopathy but not for previous myocardial infarction. In group 1 ventricular tachycardia was related to recovery (76%; p < 0.05). In group 2 tachycardia occurrence was equally divided between exercise and recovery. The electrocardiographic differences suggest that different initiating mechanisms are involved in the development of exercise-induced ventricular tachycardia. The present findings may enhance aimed drug therapy in ventricular tachycardia.