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Biomedical subjects

H W Kunz

Publications and source records attributed to H W Kunz.

At least 19 recordsLinked to original sources

Influence of drugs on activation and inactivation of hepatocarcinogenic nitrosamines.

The alkylation of liver macromolecules following in vivo administration of dimethylnitrosamine (DMN) was diminished after phenobarbital or 3-methylcholanthrene induction of the microsomal monooxygenase system, but increased after SKF 525 A pretreatment. Determination of CH2O and CH3+formation in microsomal incubation systems revealed the same results for low DMN concentrations. An interpretation is given on the basis of spectrophotometric data and electron spinresonance (EPR) measurements, by proposing that metabolic inactivation of nitrosamines is catalysed by a reduction process in which cyt. P 450 seems to be involved.

Alkylation

Effect of DMN, phenobarbital and halothane on the sedimentation characteristics of rat liver DNA.

Viable rat liver cells were isolated, and the velocity sedimentation characteristics of DNA centrifuged through alkaline sucrose gradients were studied following the administration in vivo of dimethylnitrosamine (DMN), phenobarbital and halothane. DMN application resulted in a strong decrease of sedimentation velocity, indicating generation of single strand breaks in DNA, whereas phenobarbital and halothane given in doses sufficient to induce liver enlargement did not alter the sedimentation behaviour of DNA from parenchymal or extraparenchymal liver cells.

Animals

Comparison of the haplotypes of the major histocompatibility complex in the rat. IV. The six original Ag-B haplotypes.

The six original haplotypes described in the Ag-B system were compared with their counterparts in the H-1 system. Antisera to the Ag-B haplotypes raised in inbred rats and antisera to H-1 haplotypes raised in congenic lines were tested against various panels of cell from inbred and congenic lines by the dextran and Ficoll haemagglutination methods. The private and strong public specificities detected in both systems were the same, but there were some minor differences in the intermediate and weak reactivities detected. The cross-reactivity of the antisera raised in inbred rats was broader than that of antisera raised in congenic lines. The identity of the antigenic products detected in the two systems by the dextran and Ficoll tests was further confirmed by a variety of absorption analyses and by F1 tests. This study completes the systematic serological comparison of the haplotypes of the major histocompatibility complex of the rat described originally in the Ag-B and H-1 systems.

Animals

Immune responses to some proteins and synthetic polypeptides in inbred strains of rats.

The antibody responses to DNP-bovine gamma globulin, bovine gamma globulin, human serum albumin, ovalbumin, pepsin and five synthetic polypeptides were examined in strains of inbred rats representative of eight common major histocompatibility complex (RTI) haplotypes. With each antigen the antibody response varied considerably among strains, and the data provide many potential strain and antigen combinations with which to study the genetic control of the immune response.

Animals

Litter sizes in inbred strains of rats (Rattus norvegicus).

The average litter sizes and reproductive performance of twenty-five inbred strains of rats, maintained in a conventional colony in Pittsburgh, and twenty-six inbred strains, maintained in a barrier facility at the National Institutes of Health, were calculated from data collected for periods of 3 and 10 years, respectively. There were considerable variations in both parameters in each of the two colonies studied. In addition, there were quite wide variations in male to female ratios among inbred strains (0.80 to 1.42).

Animals

Gene complex controlling growth and fertility linked to the major histocompatibility complex in the rat.

The B1 strain of rats carries a unique mutation which causes defects in growth and reproduction: the males and females are small, the testes are hypoplastic and aspermatic, and the females have a reduced reproductive capacity. The loci controlling these defects are linked to the major histocompatibility complex (MHC) as determined by segregation studies in backcross and F2 hybrid populations. The levels of pituitary hormones and somatomedin C in the B1 strain are elevated or normal, and the testosterone level is elevated relative to the size of the testes. These findings suggest that hormone deficiencies are not the cause of these defects. The genes governing these defects have been designated the growth and reproduction complex (Grc). The recessive gene regulating small body size has been designated dw-3 (dwarf-3), and the recessive gene influencing reproductive capacity has been designated f. The Grc and MHC are separable by recombination, and the dw-3 and f genes are also separable by recombination. Studies in the (B1 X DA)F2 hybrid indicate that the map distance between the Grc and the MHC is 0.6 cM. Segregation distortion due to a deficiency of RT11 homozygotes is seen in some F2 hybrid populations derived from the B1 strain. Litter size data suggest that the loss of the RT11 homozygotes is due to intrauterine death. There is no apparent sex influence on the inheritance of the Grc, at least as it is presently understood, since it can be transmitted by either females or males. The growth and reproduction complex in the rat may be the analog of the T/t complex in the mouse, and the importance of the region of the chromosome adjacent to the major histocompatibility complex in the control of developmental processes may be a general phenomenon in mammals.

Animals

Comparison of the haplotypes of the major histocompatibility complex in the rat. III. Two difficult haplotypes: H-1h (Ag-B12) in the HW strain and Ag-B13 (H-1m) in the MNR/N strain.

Two haplotypes which posed difficult problems in serological identification, those of the HW and MNR/N strains, were studied. The HW strain was originally described as a unique haplotype (H-1h), but breeding difficulties precluded its detailed serological analysis. The red blood cells of the HW strain agglutinate weakly and cross-react with antisera to the Ag-B8 group. Anti-HW antisera cross-react strongly with LEW, ACI and WKA, but absorption with these strains did not produce an adequate typing serum. By judicious selection of recipients, however, an appropriate typing reagent could be made; a particularly useful one was (BUF X MR)F1 anti-HW absorbed with WKA red blood cells. The HW haplotype segregated appropriately in a (DA X HW)F2 population. The HW strain is a low responder to poly(Glu52Lys33Tyr15). The H-1h haplotype of this strain was designated Ag-B12. The MNR/N strain had not previously been studied serologically, although its MLR type had been defined as H-1c (MLR-5). Antisera to MNR/N cross-reacted strongly with the H-1a,b,d,f haplotypes, but MNR/N red blood cells agglutinated only weakly with many antisera. An operationally monospecific reagent antiserum to the MNR/N haplotype could not be made. The uniqueness of the MNR/N haplotype was shown by F1 tests with LEW.1A, LEW.1D and LEW.1F, by various serological analyses, including production of antisera against MNR/N and in the MR strain; by segregation studies with (LEW X LEW.1D)N5 and (DA X DA.MNR)N4 segregating back-cross populations, and by grafting skin from (DA X DA.MNR)N4 homozygous and heterozygous animals to DA recipients. The MNR/N strain is a high-responder to poly(Glu52Lys33Tyr15). The MNR/N haplotype of this strain was designated Ag-B13 (H-1m). The data led to the working hypothesis that the MNR/N strain may be a recombination between the A region of H-1d and the B region of H-1c. In addition, the H-1d private specificity at the A region was probably lost by a deletion mutation which left the main complex of public specificities intact.

Animals

Comparison of haplotypes of the major histocompatibility complex in the rat. I. The Ag-B7 (H-1g) and Ag-B8 (H-1k) haplotypes.

Two haplotypes of the major histocompatibility complex of the rat, Ag-B7 and Ag-B8, have been compared with known H-1 haplotypes using the F1 skin-graft test and the dextran haemagglutination test. Both of these Ag-B haplotypes were different from the known H-1 haplotypes and determined different private specificities. The Ag-B7 haplotype was denoted as H-1g and the Ag-B8 haplotype as H-1k. The complex structure of the serologically detected antigenic products of these haplotypes was determined by means of H-1 congenic lines.

Alleles

Comparison of haplotypes of the major histocompatibility complex in the rat. II. Serological analysis of the haplotypes H-1a (Ag-B4), H-1d (Ag-B9) and H-1f (Ag-B10).

The strongly cross-reacting haplotypes of the inbred strains DA, ACI, ACP, MR, BD V and AS2, and of the congenic lines LEW.1A, LEW.1D and LEW.1F, were explored. All of these inbred strains and these congenic lines type with anti-Ag-B4 antisera raised against the DA strain, which behaved as operationally mono-specific in previously reported studies of the eight currently defined Ag-B haplotypes. Serological analyses showed that this cross-reactivity was due to antibodies against public antigenic specificities which were not previously recognized as being in the anti-Ag-B4 antisera, due to the fact that the LEW.1D and LEW.1F animals were not available for testing. With the use of appropriate antisera and of absorption studies, two haplotypes in the H-1 system were found not to have been previously identified in the Ag-B system. The animals carrying the H-1d haplotype (MR, BD V and LEW.1D) have been designated as Ag-B9, and those carrying the H-1f haplotype (AS2 and LEW.1F) have been designated as Ag-B10. With the proper absorptions, an anti-Ag-B4 antiserum can be prepared which reacts only with the DA, ACI and ACP strains, and it will henceforth be used as the operationally mono-specific Ag-B4 typing reagent. A variety of typing experiments showed that the results using antisera raised in Pittsburgh and in Prague and using the Ficoll and dextran haemagglutination methods were the same.

Alleles

Effect of maternal immunization on the antibody response of low responder rats.

The offspring of low responder F344 female rats that were immunized with poly(Glu52Lys33Tyr15) aggregated with MeBSA prior to mating showed a higher antibody response to the polypeptide antigen than did the offspring of unimmunized females. Immunization of the mothers with unaggregated polypeptide, or with DNP-BGG, did not affect the antibody response of the offspring even when high doses of antigen were used. When the polypeptide used to immunize the mothers was given as an aggregate, some crossed the placenta to the fetus. The antigen was first detected in the placenta, blood and liver of the fetus at 15 days of gestational age. After birth, it was in the liver and spleen up to 6 weeks af age, and thereafter it was present only in the bone marrow.

Animals