Viktor Stolc

ORIENTATION OF LOCI IN THE MAJOR HISTOCOMPATIBILITY COMPLEX OF THE RAT AND ITS COMPARISON TO MAN AND THE MOUSE

Among 290 F2 progeny of an r10 x ACP cross were two recombinants which allowed the loci for glyoxalase‐1 and neuraminidase‐1 to be mapped relative to the RT1.A and dw‐3 loci in the major histocompatibility complex (MHC) of the rat. In 673 progeny of the same cross there was a recombinant between ft and dw‐3, and in 403 progeny of the backcross BY1 x (BY1 x BDIX)F1 there was another recombinant between ft and dw‐3. These data, combined with those from previous studies, provide the information for constructing a detailed map of the rat major histocompatibility complex: the gene order and size in the rat are very similar to those in the mouse and different from those in man and in the other species that have been studied. Comparison of the structures of the MHC in the various species leads to a hypothesis about the evolution of the MHC which involves sequential duplications of the genes coding for class I and class II loci and an inversion in the prototypic muridae which placed the class II loci between the class I loci.

Stimulation of iodoproteins and thyroxine formation in human leukocytes by phagocytosis

Phagocytosis of inert latex microparticles increases the iodide uptake and organic binding in human leukocytes by several fold in comparison to control cells. Thyroxine, monoiodo-tyrosine, and diiodotyrosine were found after pronase hydrolysis of leukocyte proteins. An active iodide concentrating mechanism was found in the leukocytes too. The concentration of stable iodine (127I) in leukocytes was found to be 0.003 per cent, and in leukocyte proteins, 0.04 per cent.

Regulation of iodine metabolism in human leukocytes by adenosine 3′,5′-monophosphate

Abstract The rate of iodide uptake and formation of iodo-compounds in human leukocytes is regulated by adenosine 3′,5′-monophosphate (cyclic AMP). In the regulation to the dose, cyclic AMP decreases the iodine metabolism. Thyrotropin and prostaglandin E 1 increase cyclic AMP concentration in the human leukocytes. The rate of protein-bound iodine formation and total uptake of iodide by leukocytes depends on iodide concentration in the medium, that is optimal at 10 μ/100 ml. The conclusion is made, that the system adenyl cyclase-cyclic AMP response in the human leukocytes to thyrotropin, but in contrary to the thyroid gland, cyclic AMP depresses the rate of iodide metabolism.

Linkage and polymorphism of a gene controlling lactate dehydrogenase in the rat

The amount of lactate dehydrogenase subunit A in rat serum is under the control of the lactate dehydrogenase regulatory gene Ldr-1, and it is determined by two alleles, Ldr-1a(high) and Ldr-1b(low). Sex and LDH-A level segregate independently, so the Ldr-1 gene is autosomal. The genes for albino, red eye, hemoglobin, and Ldr-1 are linked (linkage group I), and their order is Ldr-1-Hbb-r-c. Our data put Ldr-1 45 cM from Hbb, and Hbb is 7 cM from c. Data in the literature separate r and c by 0.3 cM.

Control of adenylate cyclase by divalent cations and agonists: Analysis of interactions by the hill equation

Abstract The analysis by the Hill equation of the results of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), (EC 4.6.1.1) activation in human granulocytes resulted in the following findings: the adenylate cyclase agonists have no effect on guanyl nucleotide and divalent cation activation or inhibition of the adenylate cyclase activity since the Hill coefficients for Gpp(NH)p, Mg2+ and Ca2+ were not affected by (±)- isoproterenol , histamine or prostaglandin E1. The fact that the Hill coefficient for five adenylate cyclase agonists (prostaglandin E1, (±)- isoproterenol , histamine, (−)-adrenalin and (±)- noradrenalin was approximately 0.5 or less rules out the possibility that there is a cooperation among the catalytic subunits of the adenylate cyclase. The inhibitory action of Ca2+ on the adenylate cyclase activity can be attributed to a competition between Ca2+ and Mg2+ that results in a replacement of Mg2+ by Ca2+ at the intracellular Mg2+ binding site. The Hill coefficient for Mg2+ was 1.8, 2.1 and 1.7 at 0, 0.1 and 0.5 mM Ca2+ but decreased significantly to 1.1 at 1 mM Ca2+. The exposure of whole cells to Mg2+ Ca2+, prostaglandin E1 and ionophore A23187 has indicated a diverse action of divalent cations on the cyclic AMP formation. Our data suggest that Ca2+ and Mg2+ potentiate the prostaglandin E1 stimulatory effect on cyclic AMP production, Ca2+ at the extracellular and Mg2+ at the intracellular site of the adenylate cyclase complex. In contrast, prostaglandin E1-stimulated cyclic AMP formation was inhibited when Ca2+ and Mg2+ acted at the reverse sites.

Hemoglobin Polymorphism in Inbred Strains of Rats (Rattus norvegicus)

Hemoglobin phenotypes A and B were determined by polyacrylamide gel electrophoresis of erythrocyte lysates from 29 inbred strains of rats. Fourteen strains have phenotype A and fifteen have phenotype B, which are characterized by five and six hemoglobin bands, respectively. Breeding studies showed that the phenotypes are codominant and that they segregate in a simple Mendelian fashion in the (A×B) F1×A backcross. Sex and hemoglobin phenotype assort independently, and the hemoglobin phenotype is not linked to the major histocompatibility complex (RT1) and to two erythrocyte alloantigenic systems (RT2 and RT3).

Stimulatory effect of latex and zymosan particles on cyclic adenosine 3′,5′-monophosphate content in human granulocytes

Abstract Human polymorphonuclear leukocytes respond to latex beads and opsonized zymosan particles with increased cyclic AMP formation. The enhancement of cyclic AMP content in cells is related to particle concentration in the incubation medium and to the time of exposure. The temporary stimulation declines after 15 min of phagocytosis, that is in good relation to the uptake of latex particles which reaches saturation point 10 min after the addition of the beads. The cyclic AMP content in granulocytes decreases after between 15 and 30 min of incubation with latex particles. The decrease is not caused by the loss of the granulocyte viability for: (a) the incorporation of labeled methyldeoxythymidine and uridine into macromolecules continues, (b) the sensitivity of phagocytosing granulocytes to prostaglandin E1 stimulation of cyclic AMP production persists, (c) less than 10% of cells absorbs trypan blue dye after phagocytosis of latex beads. The prostaglandin synthesis inhibitors, aspirin and indomethacin, have no effect on cyclic AMP content in phagocytosing granulocytes.

Down's syndrome and mixed acute leukemia in infants

The routine use of panels of monoclonal antibodies has been complementary to the French–American–British (FAB) leukemia classification, and has unmasked the occurrence of mixed acute leukemia (myeloid–lymphoid). It is widely accepted that children with Downs syndrome (DS) have a high incidence of acute leukemia. There is an extensive body of literature emphasizing the cytogenetic findings in these children. However, information as to the immunophenotype is often limited to the lymphoid surface determinants. The authors report two children with DS whose leukemic blasts were studied with a panel of 17 monoclonal antibodies (myeloid, lymphoid, and megakaryocytic) by flow cytometric examination and were classified as biphenotypic acute leukemia. The blast population coexpressed myeloid and T‐cell surface markers. The lymphoid origin was ruled out on the basis of negative terminal deoxynucleotidyl transferase and molecular analysis demonstrating germline configuration for the JH and βTCR genes.

Linkage of Diabetes Insipidus and Agouti Genes in the Rat

Linkage of the hooded (h), agouti (A), and diabetes insipidus (di) genes was found in (ACI×DI)F1×DI backcross rats. The genetic map distance A-di for females and for males was 19±5 and 28±5 cM, respectively. However, this difference was not significant. The combined data showed the map distance to be 25±4 cM. The three-point cross showed the following corrected distances and order of genes: h-42±4-A-25±4-di. However, the linkage of h and A, although significant (x2=9.03, P<0.001), is only tentative and must be confirmed by additional studies.

GENETIC CONTROL OF BLOOD NEUTROPHIL CONCENTRATION IN THE RAT

Two phenotypes that characterize low and high neutrophil concentrations in blood were found in the rat. It is possible that either two regulating alleles control the high (Nr‐1a) and the low (Nr‐1b) neutrophil concentration or that a polygenic system affects the neutrophil concentration in blood. The F1 hybrids of four intercrosses had low neutrophil levels in blood that suggested a dominant effect of the Nr‐1b allele. The backcross progeny showed abnormal segregation of the neutrophil phenotypes. The high phenotype was expressed in only 5% of the offspring. The presence of the two phenotypes and their distribution in the backcross progeny was confirmed by the computer program SKUMIX that resolved the quantitative traits into two discrete distributions with 95% and 5% representation. Because the logistic of SKUMIX can not rule out the polygenic effect, only further breeding studies using linked markers can resolve the mechanism of the genetic control of neutrophil concentration in the rat.