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Biomedical subjects

N Grunnet

Publications and source records attributed to N Grunnet.

At least 163 records · Page 9Linked to original sources

Psoriasis in monozygotic twins: variations in expression in individuals with identical genetic constitution.

The variation in expression of psoriasis, in individuals with identical genetic constitutions, i.e. monozygotic twins, has been studied in a population-based sample of monozygotic twins in the Danish Twin Register. All verified and probable cases of psoriasis in twins, born between 1891 and 1930 inclusive, were ascertained. Results are presented of an examination of all members of index pairs in which both partners were alive. The zygosity determination was based in 94% of the pairs on very extensive serological examinations. Thirty-two monozygotic pairs were found to include at least one partner with unquestionable psoriasis (18 concordant, 14 discordant). The analyses give firm evidence of the contribution of genetic factors to the manifestation, age at onset, clinical type, course, and severity of psoriasis. A close association between psoriasis and HLA-B 13 an B 17 was found in both discordant and concordant pairs. No difference was found between partners from discordant MZ-pairs with regard to infections or marked 'stress' conditions.

Adolescent↗

Circulating levels of pregnancy zone protein: normal range and the influence of age and gender.

Serum levels of pregnancy zone protein (PZP) were measured in 506 apparently normal males and 329 normal non-pregnant females, the age range being 18 to 70 years. The estimations of PZP were performed by sensitive radio-rocket-line immunoelectrophoresis. The distribution of the data had a marked positive skew in both sexes which was reduced following logarithmic transformation. Serum concentrations in both men and women were found to increase significantly with advancing age. This increase and the mean concentrations were significantly higher in females.

Adolescent↗

Production of leucocyte poor blood. A comparison of five different methods.

The efficiency of leucocyte removal and the degree of erythrocyte loss were investigated by five different methods. The methods were: 1) saline washing of red blood cells (RBC) in the cell separator, 2) centrifugation of whole blood in glass bottles followed by removal of plasma and buffy coat by suction. 3) Imugard-Terumo filtration of whole blood, 4) inverse centrifugation of blood in a double plastic bag followed by transferring the RBC to the satellite bag, and 5) sedimentation of RBCs in CPD-dextran followed by dripping the RBCs to another glass bottle. Method no. 5 was clearly the most efficient, containing a mean of 20.8% of the offered leucocytes. After washing in saline three times this could be lowered to 7.0%. Method no. 3 was the second best method, having the lowest degree of erythrocyte loss. Methods no. 2 and 4 are approximately of the same quality. However method no. 1 was bad and can not be recommended for production of leucocyte poor blood in the present modification.

Blood Sedimentation↗

HLA antigens in atopic dermatitis. A family study.

The HLA antigens in a family with atopic dermatitis were studied. All family members with atopic dermatitis had haplotype A2, Bw35, Cw4. It has been recently demonstrated that HLA type Bw35 is found with an increased frequency in atopic dermatitis. There appears to be an inconsistent and weak correlation between atopic dermatitis and HLA-A, HLA-B and HLA-C loci.

Dermatitis, Atopic↗

Blood transfusion and human renal transplantation.

Analysis of 156 first cadaver-kidney transplants performed in one transplantation center revealed a better graft survival in the group of transfused patients compared to the non-transfused patients. The degree of statistical significance between the groups improved with increasing number of pre-transplant blood transfusions. Pregnancy had no influence on graft survival. As could be expected the frequency of lymphocytotoxic antibodies before transplantation increased with increasing number of blood transfusions. However, lymphocytotoxic antibodies seemed not to influence graft survival.

Blood Transfusion↗

Fractionation and characterization of rat hepatocytes isolated from ethanol-induced fatty liver.

A procedure for fractionation of hepatocytes according to density is presented. Hepatocytes were prepared from rats fed an ethanol-containing liquid diet, a liquid diet without ethanol, or a chow diet. The hepatocytes were fractionated in a Metrizamide density gradient and the cell fractions obtained were characterized with respect to protein synthesis, fatty acid oxidation, and esterification and ATP content. From ethanol-fed rats, two fractions of hepatocytes were obtained, one with a density of approximately 1.04 gm. per ml. and one with a density of ca. 1.08 gm. per ml. Cells from the lighter fraction contained 3 times more triacylglycerol than cells from the heavier fraction. Fifty per cent of the cells from the lighter fraction contained large (greater than 5 micron) lipid droplets as compared to 6% in the heavier fraction. The average yield from a 170-gm. rat of lipid-rich and lipid-poor cells was about 65 x 10(6) and 170 x 10(6) cells, respectively. Electron micrographs of the liver before perfusion and of the isolated and washed cell fraction revealed intact ultrastructure. Fractionation of hepatocyte suspensions from rats fed a high fat liquid diet without ethanol or a chow diet normally yielded two cell fractions with densities of ca. 1.08 and 1.10 gm. per ml. and 1.10 and 1.12 gm. per ml., respectively. The metabolic capacity of the cell fractions was unaltered by the fractionation procedure as judged by the ATP content, the rate of palmitate oxidation and esterification, and the rate of protein synthesis.

Adenosine Triphosphate↗

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↗

Alcohol metabolism at high alcohol concentrations.

The incorporation rate of tritium from (R,S)ethanol-1-3H, (R)ethanol-1-3H and (S)ethanol-1-3H in lactate and beta-hydroxybutyrate is investigated by means of a GLC method. Preliminary results show no decrease in incorporation of 3H from (R)ethanol during the period of labelling (15 min). These results indicate that either a shift in the isotope effect occurs at high concentrations of ethanol, or the results may indicate that ethanol does not exhibit a substrate inhibitory effect on alcohol dehydrogenase in the liver cells. Furthermore, the fraction of acetaldehyde metabolized in the cytosol is determined.

Acetaldehyde↗

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↗

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↗

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↗

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↗

Ethanol metabolism and lipid synthesis by isolated liver cells from fed rats.

1. The fatty acid synthesis in isolated liver cells from fed rats was studied with tritiated water as the radioactive precursor. The cells incorporated 3H20 at a rate of 1.26 mumol per min per g packed cells. 2. Addition of ethanol caused a 20% decrease in the incorporation of tritium into fatty acids. The decrease was correlated to the increase in the NAD-redox level. Probably, the decreased tritium incorporation into fatty acids during ethanol metabolism is due to a decrease in the specific activity of the NADPH used for the synthesis of fatty acids, rather than to a real inhibition of the fatty acid synthesis. 3. Ethanol oxidation via NADPH-consuming pathways and ethanol per se at a concentration of 80 mM had no effect upon the incorporation of tritium into fatty acids. 4. Fructose in a concentration of 15 mM inhibited the fatty acid synthesis by 75%, and this inhibition was further augmented by ethanol. 5. The ioslated rat liver cells oxidized ethanol at a rate of 2.72, 2.93 and 3.48 mumol per min per g packed cells at 5, 20 and 80 mM ethanol, respectively. Fructose had no effect upon ethanol oxidation neither at low nor at high concentrations of ethanol. 6. Ethanol oxidation via the non alcohol dehydrogenase pathway(s) may involve a transfer of reducing equivalents from mitochondrial NADH to cyctosolic NADP+ as judged from measurements of metabolite levels. This conclusion is supported by determinations of 14C yield in glucose from [1-14C] ethanol, and the results are taken as evidence for the presence of hydrogen shuttle activity during metabolism of ethanol, catalyzed by the NAD-dependent alcohol dehydrogenase. A metabolic scheme is proposed to account for the observed changes at low and high concentrations of ethanol.

Animals↗

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↗