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Biomedical subjects

W Wegner

Publications and source records attributed to W Wegner.

At least 19 recordsLinked to original sources

Expression of a mutated form of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO).

Phosphatidylinositol (PI) 3-kinase plays an important role in a variety of biological processes, including proliferation and apoptosis. PI3-kinase is a heterodimer consisting of an 85 kDa adapter protein (p85) containing one SH3 domain and two SH2 domains and a 110 kDa catalytic subunit (p110). Recently an oncogenic form of p85 named p65-PI3K lacking the C-terminal SH2 domain has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65-PI3K in T lymphocytes develop a lymphoproliferative disorder. Here we describe the cloning of a C-terminal truncated form of p85 expressed in a human lymphoma cell line (CO) with a T cell phenotype derived from a patient with Hodgkin's disease. As a result of a frame-shift mutation at amino acid 636, p76 is lacking most of the C-terminal SH2 domain, but contains the inter-SH2 domain and is associated with an active form of PI3-kinase. A PI3-kinase-dependent constitutive activation of Akt was detected in CO cells which was only partially reduced after serum starvation. Treatment of CO cells with the PI3-kinase inhibitor wortmannin resulted in a concentration-dependent inhibition of cell proliferation associated with an increased number of apoptotic cells. This is the first detection of a mutated form of the p85 subunit of PI3-kinase in human hematopoietic cells further underlining a potential role of PI3-kinase/Akt signaling in human leukemogenesis.

Apoptosis↗

[Problematic aspects of breeding dwarf rabbits].

Some aspects of relevance for animal protection in breeding dwarf (pet) rabbits are enumerated and discussed. The predisposition of these standard dwarfs (Dw/dw) for certain defects and diseases underlines the partial dominance of Dw; mating of these heterozygous dwarfs is an open neglect of the German animal protection law (section 11b). For feasibility of control breeders (and especially so in commercial pet rabbitries) should be obliged to guarantee unambiguous identification of breeding animals and their progeny.

Animal Welfare↗

Pathophysiological and functional aspects of the megacolon-syndrome of homozygous spotted rabbits.

The Megacolon-Syndrome is a hereditary disease of homozygous spotted rabbits (En En). Investigations have been performed on some special traits related to functional aspects of the gut in comparison to vital heterozygous spotted rabbits (En en). It was found that En En rabbits showed significantly reduced sodium absorption rates across the wall of the cecum. Consequently, the dry matter content of the ingesta was reduced at this location, whereas the content of the ashes was increased. These results indicate that a further important pathogenetic aspect of this hereditary disease is an undue liquification of ingesta in proximal parts of the large intestine. Severe clinical problems, however, resulted from obstipation. This is concluded to be a late complication due to and modified by different stressors of endogenic and exogenic origin. Thus, there are some indications that an early site of spot-gene related effects might be the small intestine. This segment of the bowel was shorter and had an increased dry matter proportion of its wall when compared with heterozygous spotted rabbits. But a decreased proportion of dry matter within the wall of the large intestine was found. The latter could be an effect of the hypothyreotic state of metabolism in En En rabbits.

Animals↗

[The problems of spotted breeds of rabbits. 4. Morpho- and histometric findings in the CNS and thyroid glands and the hormone content in blood at slaughter of hybrid rabbits, and estimation of the heterosis effect].

Morpho- und histometric investigations of brains, pituitary and thyroid glands as well as thyroid-related functional parameters in the blood of purebred and hybrid rabbits revealed a predisposition to hypothyreotic conditions in homozygous, megacolon-prone genotypes. In addition to this also a hypoganglionotic state in different gut wall localizations was confirmed; pituitary traits however did not indicate a primary contribution of this gland to the syndrome, though some alterations were found, which are interpreted as secondary sv. symptomatic. Gender influences varied hormonal characteristics and disease manifestations too: A dramatic fall in severely diseased does with respect to T3-concentration as well as a seemingly more inactive thyroid gland compared to bucks underline hormonal influences. As a consequence of these results it is concluded, that hybridisation within spotted rabbits does not amend the inclination to megacolon in animals homozygous for the K (En) gene, though it may influence its manifestation.

Animals↗

[Reflections on 100 years of animal breeding as mirrored in the Deutsche Tierärztliche Wochenschrift].

In 1893 a major component of veterinary practice derived from 4 million horses and from farm animals, whereas thousands of dogs were even slaughtered every year, especially in Saxony and Silesia. Nowadays companion animals figure as an element of ever growing importance for the practitioner. Teaching and research adapted themselves to this altered situation, research funding and professional politics not yet so completely. In former days veterinarians even presided the licensing committees for breeder animals--today the animal breeding act merely mentions them in connection with institutions of AI and ET. Misdevelopments during the Nazi period are discussed as possible causes. In analogy to refugee problems after World War II, in this decade crowding effects again challenge the profession, resulting from increasing numbers of students and European migrations.

Animals↗

[The problems of breeding spotted rabbits. 3. Variability of the pigmentation grade, ganglionic intestinal wall supply, relationship to pathogenesis--animal breeding and animal welfare aspects].

In a total of 128 animals of the German Giant Spot und the English Spot Breed grade of pigmentation and spotting pattern were investigated by photography and planimetry. A clear cut binary distribution, representing homozygous (KK) or heterozygous spot rabbits (Kk), and a strong bilateral concordance was found as well as a broad variance within both genotypical groups. Thus only a small percentage of animals bred can be compatible with mandatory fancy breed standards. Measurements of intestinal layers and neural components in well pigmented and depigmented individuals revealed an enhancement of these histological structures but a relative hypoganglionosis in distal parts of the gut in animals with predisposition to megacolon (KK, so-called chaplins). It is not yet clear whether this is symptomatic or of primary pathogenetic relevance. There were no pleiotropic deleterious effects of the K-allele in heterozygous rabbits and no correlations between the degree of depigmentation and the severity of symptoms in homozygous spotted ones, thus indicating a mode of inheritance by an incompletely dominant gene K, acting as or being linked to a recessive semilethal when homozygous. A change in breeders' attitude and breeding practices is mandatory because neither the permanent elimination of animals not "fitting" a fancy standard nor the continuous production of defective genotypes is legal.

Animals↗

Immunomodulatory activity of different blood products on the mitogen-induced human lymphocyte transformation.

Blood transfusions have an immunosuppressive effect on the recipient and induce changes in several immunological parameters. We studied the effect of homologous and autologous fresh plasma (FP), fresh frozen plasma (FFP), heparinized plasma, as well as the influence of red blood cells (RBC), CPDA-1, CPD, heparin, PAGGS-mannitol, SAG-mannitol and ADSOL on mitogen-induced lymphocyte transformation. Both homologous and autologous FP and FFP decreased the PHA and ConA response of human lymphocytes (P < 0.05). The PWM response was reduced by FP (P < 0.05). The mean t1/2 of plasma-induced suppression was approximately 38 h. Dose-dependent suppression rates were observed with pure CPDA-1 and CPD solutions. In contrast, heparinized plasma showed an elevated PHA- and ConA-induced transformation rate (P < 0.025), whereas PWM induction was unaffected. In addition, washed RBC, pure PAGGS-M, SAG-M and ADSOL solutions revealed no effect on the PHA response. Freezing, heating or recalcification of plasma resulted in an increase in the PHA response. Adenine was not immunosuppressive in vitro. We conclude that, in addition to unspecific mechanisms by CPDA-1 or CPD, an unknown plasma factor, which is susceptible to changes in temperature or storage conditions, suppresses the PHA-, PWM- or ConA-induced T-cell immune response. Further clinical studies are needed to correlate these observations with clinical phenomena.

Adenine↗

[Effect of plasma and plasma components on lymphocyte transformation].

Blood transfusions have an immunosuppressive effect on the recipient and induce changes of several immunological parameters. We therefore studied the effect of homologous and autologous fresh plasma, fresh-frozen plasma, heparinized plasma, as well as the influence of i.v. immunoglobulins on the MLC- and mitogen-induced lymphocyte transformation. We conclude from our study that, besides unspecific mechanisms, an unknown plasma factor enriched in the immunoglobulin fraction suppresses the MLC- and mitogen-induced T-cell immune response.

Humans↗

[The problem of breeding for spots in rabbits. 2. Further results on the variation of characteristics in fattening and breeding animals].

The mode of inheritance of spotting in both breeds (ES and DRS) is compatible with incompletely dominant resp. intermediate segregation, though a broad variability of spotted areas exists, indicating the influence of minor genes or other ontogenetic factors. Additional findings support the conclusion, that there is a very distinct predisposition of homozygous KK animals to develop megacolon with growing age. This also has consequences for the relative organ weight of the heart and of the adrenals in this genotype. Sporadically encountered accessory adrenal cortical tissue however did not exhibit genotypic preferences.

Adrenal Glands↗

[Effect of various blood components and additive solutions on phytohemagglutinin (PHA)-induced lymphocyte proliferation].

The effect of red blood cells (RBC), fresh plasma (FP), fresh frozen plasma (FFP) and different storage solutions (e.g. CPDA-1, CPD, PAGGS-M, SAG-M, Adsol) on the immune response was investigated in human lymphocyte cultures. The inhibitory activity was measured by determining the effect of different components on the PHA-induced T-cell proliferation. Our results indicate that the inhibitory effect is caused by an as yet unidentified plasma factor (e.g. anti-idiotypic antibodies, soluble HLA-class I or II antigens). In contrast, pure RBC or blood storage solutions revealed only minimal effects on the T-cell response.

Blood Component Transfusion↗

[The problems of spotted breeds of rabbits. 1. Fattening and body condition at slaughter, organ parameters].

Rabbits of the Giant German Spot Breed and of the English Spot Breed were bred, reared, fattened and evaluated under standardized conditions. A total of 50 animals (31 German spot = DRS; 19 English spot = ES; both derived from mating of heterozygotes) was tested, belonging to the three possible genotypes: Homozygous black (kk), heterozygous spotted (Kk, "standard animals") and homozygous spotted (KK, so-called "Chaplins"). As expected, breed differences consisted of better daily gains and higher carcass weights in DRS, but higher dressing percentages in ES. With respect to colour genotypes, only in DRS-KK depressions of daily gains and carcass weight were observed; food conversion efficiency however was even better in these animals (of both breeds), primarily because of lower feed uptake. Very distinct differences in some important organ traits could be demonstrated for those genotypes: A significantly augmented intestine (abs. and rel.) in KK-animals, specially with reference to the gross intestine--indicating a tendency to motility disturbances and/or chronic obstipation. This predisposition was underlined by the premature loss of three KK-rabbits suffering from severe corresponding symptoms. Seemingly analogous syndromes (Megacolon) in man and other species are cited, though further investigations are needed to clarify the etiology in spot rabbits. Significance of lower heart weights was stated in DRS-KK-animals, probably induced by minor activities observed in this genotype. Thus the K-gene can be classified as a subvital one when homozygous though manifestations of the symptoms obviously vary with the genetic background (breed, line) and perhaps with the environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Evaluation of the immunomagnetic beads separation technique as a routine method for HLA typing].

We analyzed the HLA data of 1,427 patients and healthy blood donors from Hamburg and Hessen, to evaluate the reliability of the immunomagnetic beads method (IMB), compared to the standard NIH and the twocolor fluorescence (TCF) typing method. Concerning HLA class I, the IMB method and the NIH-method yielded almost identical results, whereas the determination of class II HLA-DR/DQ antigens required a higher rate of retyping (20%), compared the TCF method. Hence, the IMB method should not replace the standard typing procedures, particularly in organ-donor crossmatching, unless quality controls, e.g. of HLA-genotyped families have rendered unanimous results.

HLA Antigens↗

[Raising fighting dogs].

Some experience is reported, referring to court trials of accidents involving members of the so-called "fighting dog" breeds. Analysis of the situation makes obvious that many breeders and owners of these or similar dogs demonstrate an irresponsible attitude, thereby fostering breed standards which should be corrected. A future solution of this problem and of others could only be brought about by a law, which would regulate companion animal breeding and ownership. A ban on special breeds or their integration into a "Dangerous animals act" seems for now to be feasible for breeds only which are explicitly standard-bred for aggressiveness against man. Responsible dog breeding and ownership is postulated in order to avoid a growing aversion against dogs in society, which certainly contributed to the stagnation of the dog population in the FRG during the last years.

Animals↗

[Genetic aspects of systematic mineralization disorders].

Forced selection for high daily gains and meatiness induced biological maladaptations of genetical-hormonal origin. They manifest themselves not only by well-known myopathies and predispositions to stress, but also in the so-called leg weakness of pigs, in dyschondroplasias of broilers; similar "correlated" effects are observed even in dogs and laboratory animals. As far as bones, cartilages and joints are concerned by these deficiencies in mineralization and synthesis of fibrous structures, the terms "osteochondrosis" or "osteochondropathies" were introduced recently. Manifestations and severeness of this phenomenon--induced by antagonistic selection criteria--species not always directly comparable from species to species or even from breed to breed within species. This variability can be interpreted as an indication for the compound effects of heredity and environment. Even in pure breeds like German landrace and Piétrain and even under identical rearing and fattening conditions a significant individuality was found with respect to utilization of minerals; this is documented by different biomechanical strength and mineralization of bones and cartilaginous structures in these animals and by estimates of heritability for these traits, which range slightly higher than those estimated for "leg weakness". Selective measures, therefore, against the antagonisms mentioned could be feasible. On the other hand these investigations revealed that at least in some contingents of domestic animals a biological borderline was trespassed when selecting rigorously for a few economically important traits.

Animals↗