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Biomedical subjects

N Grunnet

Publications and source records attributed to N Grunnet.

16 recordsLinked to original sources
PubMed1978

Effects of ammonia and norvaline on lactate metabolism by hepatocytes from starved rats. The use of 14C-labelled lactate in studies of hepatic gluconeogenesis.

1. Hepatocytes from starved rats were incubated with l-lactate and NH(4)Cl or norvaline, and the rates of the tricarboxylic acid cycle and of gluconeogenesis were calculated from changes in metabolite concentrations or from radioisotopic data from incubations with labelled lactate or propionate. 2. Gluconeogenesis was stimulated by the addition of 10mm-NH(4)Cl, 5mm-norvaline or 1mm-oleate by 27, 45 and 59% respectively. NH(4)Cl or norvaline also increased lactate uptake. Norvaline inhibited urea synthesis from NH(4)Cl by 85%. 3. The effects of NH(4)Cl and norvaline were not additive. However, NH(4)Cl inhibited and norvaline was without effect on gluconeogenesis from pyruvate, indicating that the two compounds act by different mechanisms. 4. The tricarboxylic acid-cycle flux was increased 80% by lactate, and NH(4)Cl caused a further 25% stimulation. Norvaline had no effect on the tricarboxylic acid-cycle flux. NH(4)Cl and norvaline tripled and doubled, respectively, flux through pyruvate dehydrogenase. 5. Total ATP formation was calculated to range from 470 to 830mumol/h per 100mg of protein, of which the basic metabolic activity accounted for 400-450mumol/h per 100mg of protein. ATP formation does not seem to be rate-limiting for gluconeogenesis. 6. Pyruvate recycling was estimated from the (14)C yield from [1-(14)C]propionate in lactate and glucose to be 10-30% of the flux of phosphoenolpyruvate to glucose. The further addition of NH(4)Cl more than doubled the recycling of pyruvate. 7. [1,4-(14)C]Succinate was rapidly metabolized by hepatocytes. About 20% of the radioactivity was recovered in glucose, indicating that succinate is also metabolized by intact (non-damaged) hepatocytes. 8. It is concluded that the metabolism of lactate by the liver is too complex to allow simple rate measurements with labelled compounds.

Adenosine Triphosphate↗
PubMed1977

Education of lymphocytes in vivo following a transient take of a matched unrelated bone-marrow graft in man.

A patient suffering from aplastic anaemia was treated by bone-marrow transplantation from an ABO- and HLA-identical, MLC- and CML-negative, unrelated donor. MLC and CML became positive after transplantation indicating that a cellular immune response had developed against lymphocyte determinants not recognized prior to sensitization in vivo. Whether these determinants are governed by genes of the HLA region is unknown at present.

Adult↗
PubMed1977

Immunological diagnosis of rejection in human renal allotransplanted patients--a prospective study.

The object of this study has been to evaluate the recipient's immunological reactivity towards donor lymphocytes in relation to rejection episodes. All recipients (20) of local necrokidneys during 1976 were immunologically monitored immediately before transplantation and subsequently twice weekly for donor-specific complement dependent lymphocytotoxic (CDC) antibodies, antibody dependent cell-mediated cytotoxicity (ADCC) and cell-mediated lympholysis (CML). Experiments were performed until graft removal or dismissal (approx. 1100 patient days). Clinical diagnosis of rejection was made independently of immunological results. All clinically suspected rejection episodes, except one, were checked by microscopy. A positive CML-test accompanied 9 out of 11 rejection episodes; the test was negative on all other occasions. Positive CDC and ADCC tests exhibited no obvious correlation with rejection episodes: positive ADCC may be more frequent in clinically uncomplicated phases. Positive CML did not generally precede clinical graft rejection. Positive CML before transplantation was observed in two cases and was followed by irreversible, accelerated acute rejections. The CML-test may prove a reliable tool in rejection diagnosis and may yield results comparable with graft biopsy without inflicting any risk on the patient.

Antibodies↗
PubMed1977

Patterns of immunological anti-donor reactivity in renal allotransplanted patients--a prospective study.

The immunological reactivity of 20 consecutive renal allotransplanted patients against donor lymphocytes were followed from the day of transplantation and subsequently twice weekly until dismissal or graftectomy. The investigations concerned Complement Dependent Cytotoxic (CDC) antibodies, Antibody Dependent Cell-Mediated Cytotoxicity (ADCC) and Cell-Mediated Lymphocytotoxicity (CML). Five patterns of immunological reactivity were observed parallelling the clinical courses. A specifically positive CML test was highly but not absolutely correlated to clinical graftrejection. Graftrejection was in general not preceeded by positive CML. The patterns of CDC and ADCC reactivity in relation to graftrejection were not evident.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1976

Depressed mixed lymphocyte culture reactivity in mothers with recurrent spontaneous abortion.

One-way mixed wife-husband lymphocyte culture (MLC) reaction as well as human lymphocyte antigen (HLA) typing were performed on 29 couples, most of whom were infertile because of recurrent spontaneous abortion, and compared with 35 fertile couples with no abortion history. The 29 couples had been selected from 280 couples with a karyotyped spontaneous abortion. A significantly depressed MLD response (P=0.04) was observed in mothers of karyotypically normal abortuses when stimulated by the fathers but not when they were stimulated by males from the fertile couples. No significant difference in the frequency of HLA-A-and HLA-B-incompatible matings, respectively, was found between the abortion and the fertile couples. It is concluded that depressed maternal cellular response to paternal stimulation can be explained as a consequence of recurrent spontaneous abortion and that it is uncertain whether this depressed response plays a role in the etiology of recurrent abortion.

Abortion, Habitual↗
PubMed1976

Cell mediated lympholysis in man: an attempt to type with cytotoxic lymphocytes.

From approximately 3,000 CML combinations, originally established in order to evaluate the qualitative and quantitative influence of the serologically defined HLA-A, B, and C antigens on cellular, complement independent cytolysis, 12 combinations were selected yielding reproducible positive cytolysis on allogenic target cells, although no HLA-antigenic sharing could be demonstrated between stimulator and target lymphocytes. These 12 CytoToxic Lymphocytes (CTL's) have been tested in parallell as "CML typing combinations" against lymphocytes from a random population sample of 100 unrelated Danes. Based on a pairwise analysis 11 of these CTL's could be classified into two groups of significantly correlated CTL's. These two groups do not define monospecific traits of allelic genetic origin as judged by a mutually positive correlation and a poor fit to Hardy-Weinberg equilibrium. The traits defined by these groups may be either partially identical or governed by closely linked loci. The same groups were identified and the same conclusions reached after exclusion of those individuals in the population sample where HLA-A, B, C, or D antigens may be targets for destruction. Thus, this study gives direct evidence that known HLA antigens are not sole target determinants in CML or that cytotoxic lymphocytes recognize HLA molecules in a different way than lymphocytotoxic antibodies. The studies underline the immunogenetic complexity of CML although this reaction is most probably governed by genes in the HLA region. It is suggested that cytotoxic lymphocytes may recognize "backbone structures" of the HLA molecules.

Cytotoxicity Tests, Immunologic↗
PubMed1976

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↗
PubMed1976

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↗
PubMed1976

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↗
PubMed1975

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↗
PubMed1975

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↗
PubMed1975

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↗
PubMed1975

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↗
PubMedDate not supplied

Direct cell mediated lympholysis by peripheral blood lymphocytes from renal allograft recipients.

Investigations of 22 kidney allograft recipients by the Direct CML-test revealed coincidence between acute allograft rejection and a positive test. 15 patients exhibited acute rejection, 3 chronic, and 4 no rejection episodes. 4 patients with acute rejection were not detected as positive in Direct CML, while 3 patients were positive without acute rejection, one having a chronic rejection. The exact role of HL-A antigens for the specificity of a positive Direct CML could not be evaluated from this material. It is concluded that the Direct CML-test may be helpful for the diagnosis of acute rejection, but that it has only limited power as the only test of recipients' response to foreign tissue.

Acute Disease↗