Female wood lemmings with the mutant X*-chromosome carry the H-Y transplantation antigen.
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Biomedical subjects
Publications and source records attributed to E Günther.
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The organization of the rat major histocompatibility complex, RT1, was studied at the DNA level by Southern blot hybridization. Genomic DNA from eight different RT1 congenic rat strains was digested by various restriction enzymes and was hybridized under stringent conditions with probes of mouse class I and class II H-2 genes. Few cross-hybridizing DNA fragments, showing no polymorphism, were seen with class II A alpha and A beta probes. The class I probes allowed for the distinction of about 8 to 19 cross-hybridizing bands, which exhibited extensive polymorphism. With the use of five RT1 recombinants, about 20% of the DNA fragments could be mapped to the RT1.A region, which codes for the ubiquitously expressed class I antigens, and about 80% to the RT1.C region-determining class I-like antigens, which are different from RT1.A antigens with respect to tissue distribution, restriction function in immune responses, and allograft rejection. The number of class I genes present in the rat genome and the possible relationship of RT1.C to H-2Qa, Tla of the mouse are discussed.
The influence of genetic factors on the susceptibility of the rat to cationic antigen-induced in situ immune complex glomerulonephritis was investigated. The levels of proteinuria developing in 11 inbred strains of rats differing in MHC and in genetic background varied markedly. Susceptibility was not MHC associated but resided in the genetic background.
Studies on the major histocompatibility complex of the rat (RT1) will be summarized, which demonstrate the existence of a cluster of class I-like genes differing in expression, function and complexity of their organization from the "classical" class I genes, the gene products of which restrict antigen recognition by T lymphocytes. The characterization of the respective gene region (RT1.C) and its products is based on data obtained with classical genetic, molecular genetic, biochemical and immunological methods. It turns out that the RT1.C region and RT1.C antigens are in many aspects homologous to the H-2Qa region and H-2Qa antigens, respectively, of the mouse.
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In 84 patients with an acute myocardial infarction clinical signs, measurement of the pressure of the pulmonary arteries and radiogramme of the thorax were used and compared for the estimation of the left heart insufficiency-particularly of an increase of a preload. The value of a standardized course series of radiogrammes of the thorax as a non-invasive investigation method in contrast to the invasive method of the pressure measurement of the pulmonary arteries was discussed. Advantages and disadvantages of the two methods were critically shown, since only in about 60% a correspondence was to be recognized.
It is reported on 191 patients of an intensive care unit, in whom for the purpose of the prophylaxis of thromboses and thromboembolic complications a low-dose heparinisation was carried out. For comparison served the documents of 137 patients who were admitted to the same department for homogeneous reasons but had not been treated prophylactically with anticoagulants. In no case more massive haemorrhages developed which might have compelled us to interrupt the therapy. In spite of the low-dose heparinisation 4 pulmonary embolisms as well as thromboses of the abdominal aorta, the radial artery and the coronary arteries were the result; they were confirmed autoptically . Thus the low dose heparinisation does not represent a sufficient protection against the thromboembolic complications for patients with internal diseases who are confined to bed. The demand is made to establish the individual need of heparin and to adjust the heparin dose according to this.
Fragments of the E. coli chromosome that carry the dnaB groPB534 or groPB612 alleles have been cloned into a cosmid vector. The resulting recombinant plasmids contained the genes uvrA, groP (B534 or B612), and lexA. Further subcloning into high copy number plasmids, during which the uvrA and lexA genes were removed successively, yielded a groPB534 and groPB612 DNA fragment of about 2.4 kb each. Both fragments contained an overlapping 1.8 kb segment of DNA in which the sites of all restriction enzymes tested were identical. The size of these dnaB gene fragments were further delimited by deletion analysis. In E. coli groPB534 in which lambda wild-type and lambda pi A mutants do not replicate (Georgopoulos and Herskowitz 1971) phage replication is rescued if the strain contains the groPB534 gene on high copy number plasmids. On the contrary, in E. coli groPB612, which is temperature-sensitive for its groP character, replication of lambda and lambda pi A is abolished at 30 degrees C if the strain contains the groPB612 recombinant plasmid. On the other hand, replication of lambda pi B remains unaffected whether or not the groP strains harbor the isogenic dnaB gene-containing plasmid. The results suggest that within the cell not only the quality but also the relative amounts of dnaB and lambda P protein are crucial for lambda phage replication.
After NG mutagenesis an FP2 donor was isolated which exhibited an enhanced conjugational capacity for chromosomal genes. The recombination frequency was increased by two orders of magnitude as compared to the parental strain. In plate matings recombinants arose at a frequency up to 5 X 10(-1) per donor cell. Late markers also recombined efficiently. An Hfr state of the donor strain was supported by (i) the high recombination frequency, (ii) the incompatibility reaction with plasmid pRO271 (= FP2::Tn401) and (iii) the clearcut transfer kinetics in interrupted matings, even for a late marker.
Three loci coding for different steps in the pathway of cysteine biosynthesis have been mapped by R68.45-mediated coconjugation analysis. The cysteine auxotrophic mutants could be subdivided into sulfite and sulfide-requiring mutants. Sulfide-requiring mutants (cysIV group) were localized at a single position between pyrF and pur-67, while sulfite-requiring mutants (cysI and cysII) mapped at two different regions. The cysI group was also localized between pyrF and pur-67, although more distal to pyrF than the cysIV group. This group included the cys-54 marker, which has been mapped previously. The second group of sulfite-requiring mutants, designated as cysII, was cotransducible with hisI and localized at the end of the PAO chromosomal map. This location was also confirmed for the marker cys-59. The marker cys-59 (which was cotransducible with hisI) was cotransferred by R68.45-mediated conjugations with both the late marker pur-67 and the early marker ilv-226. As the late marker hisI was positioned at about 60-65 min (Herrmann and Günther, in press) the length of the PAO chromosome was estimated to be about 70 min.
Two types of biochemically defined class I major histocompatibility complex (MHC) antigens are found in the rat, RT1.A antigens that are ubiquitously expressed and RT1.C antigens which so far are detectable only on certain cell types, notably B and T lymphocytes. It is shown that the cytotoxic T lymphocyte response to minor H antigens of the LEW strain, including the H-Y antigen, and to TNP-modified syngeneic lymphoid cells is restricted by RT1.A but not RT1.C gene products. This conclusion is based on bulk culture assays including cold target inhibition tests and limiting dilution experiments using recombinants between the RT1a and RT1u haplotypes. The possibility that class I MHC antigens exist which have no major restriction function is discussed.
A new allele of esterase-13 was detected in various laboratory inbred strains of Rattus norvegicus and designated Es-13c. The activity of ES-13 towards a range of chromogenic substrates, inhibitor profile, isoelectric points and retardation coefficients on polyacrylamide gel electrophoresis were determined. The organ specific expression of ES-13 alleles was investigated and it was shown that kidney homogenates contained a factor which modified the liver enzyme banding pattern in vitro. The features of ES-13 from the rat indicated homology between this esterase and ES-3 from the house mouse, Mus musculus domesticus.
Working with the recently available recombinant haplotypes of the rat major histocompatibility complex (MHC)--RT1, we investigated the effect of various types of blood transfusion (BT) on allograft prolongation, including blood identical for the whole RT1 haplotype with that of the donor or for only a part of it. One or two milliliters of donor blood significantly prolonged graft survival in the (LEW X BN)F1----LEW or the LEW X 1W----LEW X 1A combination. The optimal regimen consisted of two BTs given 15 and 7 days prior to grafting; BTs given at day -30 were ineffective. A BT given on the day of the operation was effective, but sequential BTs after grafting did not further increase graft survival. In the (LEW X BN)F1----LEW combination, blood from congenic LEW X 1N rats significantly prolonged graft survival, but third-party BTs were ineffective or had only a borderline effect when transfused (1 ml, 8 times) within the three months before transplantation. This showed the major role of the RT1 system as well as the specificity of the model. Although the survival of LEW X 1A heart grafts transplanted into LEW X 1W recipients could not be significantly prolonged by donor blood, with the reverse--and "weaker"--combination (LEW X 1W----LEW X 1A), 2 ml of donor blood led, in all cases, to greater than 100 days graft survival. In this last combination, third-party BT (LEW X 1N) was again totally ineffective. Blood from RT1-recombinant rats was used to test the role of the respective RT1.A, B, and C regions, in the enhancing effect. BTs from LEW X 1AR2 or LEW X 1WR2 recombinants--sharing, respectively, RT1.C and RT1.A with the graft donor--were only moderately effective, as compared with BTs from the graft donor. On the other hand, LEW X 1WR1 BTs--sharing the RT1.A and RT1.B regions with the graft donor--had a much more powerful effect on heart survival. The results strongly suggest that the RT1.B region (coding for Ia-like antigens) must be shared by the graft and blood donor in order to mediate a significant graft prolongation.
A potent mitogen for T lymphocytes of various species has recently been isolated from the supernatant of cultured Mycoplasma arthritidis organisms (MAS). In the mouse, reactivity to this mitogen has been observed to be controlled by the I-E subregion of the major histocompatibility complex. We have analysed the responses of spleen cells from several inbred rat strains covering practically all known haplotypes of the major histocompatibility complex of the rat (RT1). Unlike in the mouse, all of these responded well to MAS, except for the BN rat strain, which is a low responder to all T-cell mitogens, including phytohaemagglutinin and concanavalin A. This unresponsiveness, however, appeared to be unrelated to the RT1 haplotype, since LEW.1N rats carrying the same RT1n haplotype as BN animals responded well. Mice of the strain C57BL/6 are non-responders to MAS, but--as previously shown--their spleen cell responses can be reconstituted by the addition of 2-mercaptoethanol. No such reconstitution was observed for the low responsiveness of BN rat spleen cells. Stimulation with MAS induced high titres of interferon (presumably gamma interferon) in spleen cells from all rat strains tested. Spleen cells from BN rats produced lower interferon activities than those from other strains.
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Today, as far as we know the multiple complications of different organs in connection with an acute pancreatitis are due to an enzyme intoxication and/or an endotoxinaemia. The paper reports about experimentally results which establish this view. In addition the favourable effects of the peritoneal dialysis on the course of the disease is emphasized by a prospective study. Important factors which must be considered in view of the effectiveness of the method are quoted.
In 1977/78 5418 childless human males were examined andrologically and followed up 24-36 months later. Depending upon these results a partial correction of the evaluation criteria of spermatological findings is necessary. The normal values of sperm density and motility rate are obviously lower than hitherto reported in the international nomenclature. Fructose concentration in seminal plasma does not allow to make reliable statements on the prognosis of fertility.