Severe transfusion reaction to donor plasma containing HLA antibody.
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Biomedical subjects
Publications and source records attributed to N Grunnet.
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To examine the effect of intensive physical exercise on interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha) and lymphocyte subsets, eleven elite and well-conditioned runners were tested in relation to a five-kilometer race. IL-2 was significantly decreased (p less than 0.01) immediately after the exercise and significantly increased after 24 hours (p less than 0.05), compared to the pre-exercise values taken at steady state. TNF alpha was significantly increased after 2 hours (p less than 0.05), and returned to habitual values after 24 hours. In the steady state at rest, elevation of HLA-DR+ cells was observed in all runners compared with control subjects (p less than 0.05), indicating a persistent activation of lymphoid cells. In connection with exercise a significant increase in NK cells (CD16+) was observed (p less than 0.01). The T-helper/T-suppressor (CD4+/CD8+) ratio was significantly reduced in connection with physical activity (p less than 0.01). In seven runners the ratio was reduced to a value of less than one. This decrease was observed immediately after the exercise, followed by increased ratios 2 hours later (p less than 0.01), due to oppositely directed quantitative changes of the CD4+ and CD8+ cell populations. After 24 hours the ratios returned to habitual levels. Furthermore, we confirmed an increase in the total number of granulocytes in connection with exercise (p less than 0.01), and observed a decrease in absolute numbers of lymphocytes two hours after exercise (p less than 0.01). We emphasize the importance of obtaining information about physical activity within the previous 24 hours before measuring white blood cell parameters.
Pregnancy outcome was investigated: 1) in fifteen women suffering from idiopathic recurrent spontaneous abortion (RSA) and who had experienced pregnancies with two different partners, and 2) in the mothers, the sisters and wives of the brothers of 90 consecutively referred women with RSA. After adjusting for ascertainment bias, the patients with 2 partners had an abortion rate of 72% with the first spouse (significantly increased compared with the expected rate) and a nearly 100% abortion rate with the second spouse. This suggests that, in the main, RSA is not partner-specific. The sisters of the patients had suffered a significantly increased miscarriage rate (25.3%) compared with the observed rate in a Danish control group. The wives of the brothers had an abortion rate of 18.8%, which was not significantly increased vis-à-vis the controls. The sisters showed a lifetime incidence of RSA (10.6%) which was significantly greater than comparable estimates in the literature. These results suggest the existence of a familial predisposition to spontaneous abortion in families where RSA occurs.
The aim of the study was to investigate the correlation between two types of assay measuring specific products of complement C3 activation and their clinical application. Complement C3d split product was estimated using double-decker rocket immunoelectrophoresis (DD-RIE) and measurements of C3d neodeterminants exposed after C3 activation was carried out with an enzyme-linked immunosorbent assay (ELISA). A total of 595 blood samples were measured in parallel in the DD-RIE and the ELISA test systems. The samples originated from blood donors (44), uraemic patients undergoing dialysis (135), serial samples from rheumatoid arthritis (RA) patients during steroid treatment (88) and 328 randomly collected patient samples. The mean values for DD-RIE and ELISA (+/- 1 SD) for the 595 samples were 48 (+/- 20) mU/l and 48 (+/- 28) mU/l respectively. The interassay coefficient of variation (CV) in the ELISA was 18%. The Spearman rho-correlation coefficient between the two assays was 0.63 for all 595 samples. The mean values using ELISA and DD-RIE were practically identical for the 328 successively incoming samples, the samples from the 135 dialysis patients and the 44 donors. In RA patients a higher mean value was found for the 88 samples using DD-RIE than ELISA. In the majority of patient samples there was a good correlation between the two assays. However, the ELISA appears to be more sensitive in detecting acute complement activation and to give lower levels in RA patients with chronic complement activation.
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In a three generation family with 27 members we examined a relationship could be found between spontaneous pneumothorax and HLA-haplotypes, alpha 1-antitrypsin phenotypes or concentration or lung volumes and ventilatory capacity. Eight individuals in the family suffered from spontaneous pneumothorax. No relationship with the investigated markers could be found in this informative family. All patients showed normal lung volumes and ventilatory capacity after recovery.
We performed a questionnaire study among 413 consecutive voluntary unpaid blood donors being bled for the first time. About 50% were aged below 26 years, 93% were employed or students, and 50% of the donors came from families with other blood donors. The motives to donate blood were investigated. As motives we found: altruistic and humanitarian reasons in about 98%, to obtain a greater well-being in about 60%, tradition at the place of employment or in the family about 35% each. The importance of blood tests taken in connection with the blood letting was analysed. We could not find any support for the hypothesis that blood donors in Denmark enroll as donors to be tested for HIV antibodies.
Hepatocytes from male or female rats were cultured for up to 2 weeks in a modified Waymouth medium supplemented with 0.1 or 1.0 microM dexamethasone, 10 nM insulin, and 0.1 nM glucagon with or without addition of phenobarbital, methylcholanthrene, or isoniazid. The activities of testosterone hydroxylases were measured in the intact cell monolayer and in the corresponding microsomal fraction. Aniline hydroxylase was measured in cell homogenates. In the presence of 0.1 microM dexamethasone the testosterone hydroxylase activities varied differently in hepatocytes from male and female rats during the culture period. The activities of 6 beta- and 15 alpha-hydroxylases increased in female and were unchanged in male hepatocytes, while 16 alpha-hydroxylase activity increased in female and decreased in male, and 2 alpha- and 7 alpha-hydroxylase activities were unchanged in both male and female hepatocytes during the culture period. Increasing the dexamethasone concentration to 1.0 microM caused an increase in 6 beta- and 15 alpha-hydroxylase activities in cultures of hepatocytes from both sexes, whereas an increase of 2 alpha- and a decrease of 7 alpha- and 17-hydroxylase activities were found only in cultures of hepatocytes from female rats. Addition of phenobarbital caused an increase in the activity of 7 alpha-hydroxylase in both male and female hepatocytes, while the effect on the other hydroxylases differed with the sex. In hepatocytes from male rats phenobarbital addition decreased the activities of 2 alpha- and 16 alpha-hydroxylases, while these were increased or stable after addition of phenobarbital to hepatocytes from female rats. The activity of aniline hydroxylase was increased at Day 1 and declined afterward. The results demonstrate that the activities of different steroid hydroxylases are inducible and can be directly measured in monolayers of hepatocytes from rats.
In a regional blood transfusion centre, we observed 45 episodes of hyperlipidemic plasma among the 45,000 units produced from 12,000 unpaid volunteer blood donors during a two year period. Analysis of fasting serum cholesterol and serum triglycerides showed that 26 of the 45 were raised in either one or both of the values. Dietary instructions were given, in most cases through their general practitioners, who were informed of the results. Control of serum lipids taken in average 9.5 weeks later by the general practitioner showed a remarkable decrease in triglyceride and a slight decrease in serum cholesterol. Among the 26 we found one case of non insulin dependent diabetes mellitus, three possible and three chronic alcohol abusers. Based on these findings, fasting serum cholesterol and serum triglyceride are now analysed in donors, who repeatedly show hyperlipemic plasma.
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A co-culture system of cerebellar granule cells (glutamatergic neurons) and hepatocytes has been developed. Petri dishes divided in halves by a temporary septum were coated with poly-L-lysine and cerebellar granule cells plated in one of the compartments. Five days later hepatocytes were plated in the other compartment and after 2 days the septum was removed and the two cell types shared the same culture medium for a period of 5 days. During this period of time cultures of neurons and hepatocytes kept separately or in co-culture exhibited identical characteristics with regard to activities of pyruvate kinase and glucokinase (hepatocytes), aspartate aminotransferase (neurons) as well as evoked transmitter release (neurons) and content of cytochrome P-450 (hepatocytes). The results show that it is possible to maintain neurons and hepatocytes in co-culture sharing the same culture medium for a prolonged period of time. Such a system may serve as a pharmacological model to study interactions between liver and brain cells with regard to neuroactive drugs.
Epidemiological evidence suggests a reduced rate of chronic inflammatory diseases and ischaemic heart disease in populations with a high consumption of fish. This has been ascribed to the high content in sea food of polyunsaturated fatty acids (PUFAs), belonging to the n - 3 family. We have studied neutrophil and monocyte chemotaxis in 12 healthy males before and after 6 weeks supplementation with cod liver oil, corresponding to 5.3 g n - 3 PUFAs daily. Neutrophil and monocyte chemotaxis were investigated using the under agarose technique with N-formyl-methionyl-leucyl-phenylalanine (N-FMLP) and autologous serum as chemoattractants. Neutrophil chemotaxis towards both chemoattractants and monocyte chemotaxis towards N-FMLP were significantly reduced after supplementation with cod liver oil.
Sharing of major histocompatibility antigens between spouses has been claimed to play an aetiological role in couples with unexplained, habitual spontaneous abortions. On the other hand there is evidence that a subset of habitually aborting women exists, in whom autoimmune aberrations seem to be of importance. In the present study, 56 couples with unexplained habitual abortions were histocompatibility typed for HLA-A, -B and -DR specificities, as were a group of 33 fertile control couples with two or more children and no spontaneous abortions. The DR-typing was done partly by use of the restriction fragment length polymorphism (RFLP). There was no significant difference in the distribution of histocompatibility antigens between the habitually aborting women and the control women. No increased HLA-antigen sharing could be demonstrated between spouses in aborting couples compared with controls, neither in each single locus nor in the combination of all loci (all P-values greater than 0.2). Neither could any increased HLA-antigen sharing in sub-groups of aborting couples with and without autoimmunity be demonstrated. It can be concluded from these data that compatibility between spouses for HLA-A, -B and DR-antigens per se only plays a minor role in the aetiology of habitual abortion.
A possible relationship between recurrent spontaneous abortions and autoimmune abnormalities was studied. Eight serological autoimmune or autoimmune-correlated parameters were investigated in 91 women with unexplained recurrent abortions (greater than or equal to 3 consecutive, spontaneous abortions) and 89 fertile control women. Five parameters were seen significantly more frequently in 19 women with at least one second trimester miscarriage which had been associated with severe intrauterine growth regardation (IUGR), than in controls. Seventeen of these 19 patients (89%) had at least one positive autoimmune parameter, compared to 15 of 72 patients (21%) with no second trimester abortions with IUGR (P less than 0.0001) and 14 (16%) of the controls (P less than 0.0001). No single autoantibody characterized patients who exhibited a significant accumulation of autoimmune parameters. These findings may suggest that women with recurrent abortions, in whom autoimmunity is thought to play a role, cannot be identified merely by one laboratory assay, such as that for cardiolipin antibodies, but must be defined by positivity of several criteria. Using our own test panel, preliminary clinical and serological criteria have been set up for the definition of an autoimmune-associated recurrent abortion condition. Twenty-three per cent of the patients in our material fulfilled these criteria, and seven out of nine of these women (78%) have to date been treated successfully with heparin/aspirin during pregnancy.
Insulin-dependent diabetes mellitus (IDDM) is associated with an increased risk of coronary artery disease (CAD). There is some evidence that polyunsaturated fatty acids of the marine n-3 type (n-3 PUFA's) may offer protection against CAD. We have studied the effect of short-term dietary supplementation with n-3 PUFAs on lipids, haemostasis, neutrophil and monocyte chemotaxis in 10 patients with IDDM. The patients were given 4 g daily of n-3 PUFAs (fish oil) for 6 weeks and were investigated before and after the supplement. No significant effects on platelets or haemostasis were observed. High density lipoprotein (HDL)-cholesterol significantly increased, and triglycerides and the ratio of total cholesterol to HDL-cholesterol significantly decreased. Monocyte chemotaxis was unaltered, while neutrophil chemotaxis significantly increased after fish oil. The finding of an improvement in neutrophil chemotaxis after supplementation with n-3 PUFAs to patients with IDDM needs to be confirmed in future studies.
Histocompatibility typing was done on 63 women with idiopathic, recurrent abortions (greater than or equal to 3 consecutive, spontaneous abortions; summarized abortion rate: 92.8%), 112 of their full siblings and 101 parents. The distribution of full sisters sharing 2, 1 and 0 of the probands' haplotypes diverged from expected Mendelian segregation (p less than 0.05). Sisters sharing both the probands' haplotypes had an abortion rate of 59.1%, haploidentical sisters had an abortion rate of 25.0% whereas 6.3% of the pregnancies of the 0 haploidentical sisters had ended in miscarriage. The probands' HLA haplotypes included a significant (p less than 0.02) excess of HLA-A, B haplotypes which have previously been shown to exhibit features of positive linkage disequilibrium in Danes. Analysis of abortion rates among the probands and their siblings indicate that the idiopathic recurrent abortion syndrome and probably also the tendency to some sporadic abortions are inherited conditions determined by genes in the HLA region. The presented data may be compatible with an additive polygenic mode of inheritance with exclusive or predominant phenotypic expression in females controlled by an HLA linked spontaneous abortion susceptibility region (SASR).
Conditions for maintaining the activity of alcohol dehydrogenase in cultures of hepatocytes isolated from female rats were studied. The activity of alcohol dehydrogenase in freshly isolated cells was 1.7 U/mg DNA. When cultured, the activity declined 20% after one day of culture, irrespective of the culture conditions. In a conventional medium with 5 mM glucose the activity after one week of culture was only 30% of that initially measured in culture. Addition of 25 mM glucose or a high concentration of amino acids delayed the decrease. When these compounds were added together it was possible to maintain the initial activity for one week, but the activity declined during the following week. Addition of growth hormone had no effect during the first week of culture but abolished the fall during the second week. The initial metabolism of ethanol was 0.65 mumol/min x mg DNA and declined to two-thirds during the 2 weeks of culture.