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Biomedical subjects

N Grunnet

Publications and source records attributed to N Grunnet.

At least 181 records · Page 10Linked to original sources

Cell mediated lympholysis in man. The impact of HLA-C antigens.

From a population of individuals, all HLA-A, B, and C tissue typed in relation to the Sixth International Histocompatibility Workshop, an experimental investigation has been performed to study the influence of the HLA-Cwl, w2, w3, w4, and w5 antigens in the Cell Mediated Lympholysis (CML) test. The average cytolysis obtained due to allogenic attack of one HLA-C antigen equals 12.6%, but like the HLA-A and B antigens, HLA-C antigens exhibit differences with regard to sensitizing and target potential. This indicates either a heterogeneity of these antigens or the existence of separate CML determinants. It is concluded that the HLA-C antigens may account for the cytolysis observed in some of the combinations exhibiting cytolysis which cannot be explained by the HLA-A and B antigens.

Epitopes↗

Hyperacute rejection of a kidney allograft may be caused by cytotoxic lymphocytes.

A case of hyperacute rejection of a kidney allograft is described in relation to the clinical, patho-anatomical, and immunological findings. An 18-year-old male was allotransplanted for the third time with a necrokidney from an unrelated HLA-A and B, full house identical and blood group ABO identical donor. Serological crossmatches performed with recipient sera harvested before and after transplantation were negative. In spite of this, the kidney suffered hyperacute rejection according to clinical and patho-anatomical criteria. The cellular, complement independent cytolytic capacity of recipient lymphocytes drawn before and after transplantation against donor lymphocytes was tested by the direct Cell Mediated Lympholysis (CML) test. This test was positive 24 hours after transplantation, whereas it had been negative before this. Lymphocytolysis was enhanced by inactivated recipient serum harvested before and after transplantation. These findings suggest that hyperacute rejection of a kidney allograft may be ascribed to presensitized, not necessarily circulating, effector lymphocytes either alone, or in concert with antibody(ies) not disclosed by conventional crossmatching.

Acute Disease↗

Occurrence of lymphocytotoxic lymphocytes and antibodies after corneal transplantation.

Twentyfive recipients of penetrating corneal grafts were investigated for the presence in the peripheral blood of cytotoxic lymphocytes by the Direct Cell Mediated Lympholysis (Direct CML) test as well as for lymphocytotoxic antibodies. Eight patients presented a positive Direct CML. Six of these patients have shown clinical signs of graft rejection, while two patients had a clinically uncomplicated course. Only one of the 25 patients had lymphocytotoxic antibodies. This patient showed a negative Direct CML, and a clinically uncomplicated course.. The findings seem to imply that recipients of corneal grafts can be immunized by their grafts and that cytotoxic lymphocytes in peripheral blood appear frequently in those patients showing graft rejection.

Adult↗

Metabolism of 1-3H-ethanol by isolated liver cells. Time-course of the transfer of tritium from R,S-1-3H-ethanol to lactate and beta-hydroxybutyrate.

Parenchymal cells isolated from the liver of 24 h fasted rats were incubated with 65 mM R,S-1-3H -ethanol plus 3 mM pyruvate as substrates in the absence and presence of 1.7 mM 4-methylpyrazole. Metabolite levels and the time-course of the transfer of tritum from ethanol to lactate and beta-hydroxybutyrate was measured during the first 15 min of ethanol metabolism. The time-course of the loss of tritium from 2-3H-L-lactate and 3-3H-beta-D-hydroxybutyrate in experiments identical to the above-mentioned was estimated. A GLC method for the isolation of lactate and beta-hydroxybutyrate and the preparation of 2-3H-L-lactate and O-3H-beta-D-hydroxybutyrate is described. The incorporation rate of tritium from ethanol into lactate and beta-hydroxybutyrate decreased with time. Addition of 4-methyl-pyrazole decreased the incorporation rate roughly proportional to the decrease in ethanol and acetaldehyde metabolism. The observed incorporation rates of tritium to lactate were corrected for the detritiation rates measured in experiments with I-3H-L-lactate and 3-3H-beta-D-hydroxybutyrate as substrates. The rate of extramitochondrial acetaldehyde oxidation was calculated from the corrected initial rates of incorporation of tritium into lactate to 0-0.4 mumol min-1 (ml of cells)-1.

Acetaldehyde↗

Materno-fetal ABO incompatibility as a cause of spontaneous abortion.

In a series of 288 spontaneous abortions occurring during the first 16 weeks of gestation, simultaneous karyotyping and ABO blood grouping of 555 of the parents were carried out. In 74 of the 288 chromosome-analyzed abortuses, the ABO blood group of the fetus was determined by the immuno-fluorescence technique and the mixed cell agglutinating reaction in fetal tissue. The results of the blood grouping were compared with the ABO blood group frequencies of 8818 blood donors from the same area. Among abortuses with normal karyotype, a significantly higher frequency of ABO incompatibility was found between mother and fetus (p smaller than 0.005) and also between mother and father (P smaller than 0.01) in comparison with abortuses with abnormal karyotype. Furthermore, the ABO blood group frequencies of the karyotypically normal fetuses deviated significantly from those of fetuses with abnormal karyotypes (P smaller than 0.001). No significant difference was found when the total ABO frequencies of the abortuses and of their parents were compared with the frequencies in the control group. It is concluded that the ABO incompatibility between mother and fetus is likely to be a cause of early spontaneous abortions, but almost exclusively in chromosomally normal abortuses. In the present series of cases, the maximum fraction of abortions caused by materno-fetal ABO incompatibility is estimated to be 18%.

ABO Blood-Group System↗

Cell mediated lympholysis in man. Patterns of killing power in relation to the HL-A system.

In general it can be said that the HL-A (LA and FOUR) antigens seem to be of major qualitative and partly quantitative importance for the degree of destruction in Cell Mediated Lympholysis (CML). This has been established by analyses of 1299 effector/target combinations involving 97 different healthy individuals. The main observation is that the cytolytic capacity of MLC effectors is positively ranked with the number of HL-A (LA and FOUR) antigens introduced by the incompatibility between stimulator, effector and target lymphocytes. However, the fact that not all cytolytic situations can be explained by the HL-A system stresses that other specific antigens (Target Determinants) may interfere with the Cell Mediated Lympholysis.

Antigen-Antibody Reactions↗

Cell mediated lympholysis in man. Varying strength of the HL-A (LA and FOUR) antigens as sensitizing or target determinants.

The gene products of the LA and FOUR loci of the human Major Histocompatibility Complex (MHC) are generally considered to be a major target in the Indirect Cell Mediated Lympholysis (ICML) test. Within most experiments, a positive correlation exists between the number of HL-A antigens challenged and lympholysis. When different experiments are collated this correlation is less obvious. This discrepancy might be caused by differences between the individual HL-A antigens involved in the afferent phase (MLC) and/or the efferent phase (CML). In 28 experiments involving 97 unrelated individuals we have compared statistically 12 different antigens governed by the LA and FOUR loci. When only one of these antigens is challenged in ICML, target lymphocytes are lysed to different degrees allowing a significant classification of the antigens into different groups, which do not coincide with the classification in the LA and FOUR series antigens. It is concluded that the antigens of the HL-A system are not of equal importance when challenged separately in ICML. The existence of a separate CML locus and a corresponding linkage disequilibrium to the SD loci of the MHC region is suggested.

Antigen-Antibody Reactions↗

Cell mediated lympholysis in man. The HL-A third locus antigen, AJ (W20) as sensitizing and/or target determinant.

The Indirect Cell Mediated Lympholysis (ICML) test has become a reliable in vitro tool in investigations of the immunogenetic background of the cellular immune response. It is well established that the antigens of the LA and FOUR loci of the human Major Histocompatibility Complex (MHC) or antigens governed by closely linked loci exhibiting a marked linkage disequilibrium are of major qualitative and quantitative importance in ICML. This communication is concerned with the importance of the HL-A third series antigen AJ (W20) on lympholysis in ICML. From investigations of 47 combinations where only the AJ (W20) antigen may be attacked, it is concluded that this antigen is, in itself, a poor ICML target determinant, but that AJ (W20) may function as a stronger ICML target determinant in concert with a FOUR antigen, although the actual FOUR antigen cannot be attacked.

Antigen-Antibody Reactions↗

Direct cell mediated lympholysis. A test of allograft-rejection in human kidney recipients.

In kidney transplanted patients a clear coincidence was observed between clinical signs of allograft rejection and the presence in the peripheral blood of killer cells able to lyse either PHA lymphoblasts from the actual donor or selected unrelated individuals. In recipients with non-immunological complications such as leakage on the graft ureter or primary anuria caused by renal ischaemia, no cellular cytotoxicity against specific or selected target cells was observed. The specificity of this Cell Mediated Lympholysis in two of the cases reported could not be explained by the serologically detectable HL-A antigens, indicating the existence of other determinants of importance for the killing capability of in vivo produced effector cells.

Adult↗

The effect of acute and prolonged ethanol treatment on the contents of coenzyme A, carnitine and their derivatives in rat liver.

1. CoA, acetyl-CoA, long-chain acyl-CoA, carnitine, acetylcarnitine and long-chain acylcarnitine were measured in rat liver under various conditions. 2. Starvation caused an increase in the contents of these intermediates, except that of carnitine. 3. A single dose of ethanol had no effect on CoA content, whereas those of acetyl-CoA, acetylcarnitine and carnitine were increased and those of long-chain acyl-CoA and acylcarnitine were decreased. 4. Four weeks' adaptation to ethanol consumption did not change the effect of ethanol administration on these metabolites. 5. It is suggested that ethanol directly increases hepatic fatty acid synthesis and esterification. It is also suggested that this change is reversible and limited to the period of ethanol oxidation. 6. It is demonstrated that ethanol-induced triglyceride accumulation is not related to carnitine deficiency.

Acetyl Coenzyme A↗