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Biomedical subjects

R Wanke

Publications and source records attributed to R Wanke.

45 records · Page 3Linked to original sources

Multiple consequences of human growth hormone expression in transgenic mice.

Transgenic mice harbouring growth hormone gene constructs have been produced by DNA microinjection into pronuclei of fertilized oocytes. We examined transgenic mice carrying a mouse metallothionein I-human growth hormone (mMT I-hGH) fusion gene. Here, we present our results concerning gene integration, gene expression, and phenotypical, clinical and pathomorphological alterations found in mice expressing the hGH transgene. Body and organ growth was significantly increased in transgenic mice, whereas fertility was found to be reduced. The life-span was markedly shortened indicating detrimental side-effects of the high levels of circulating hGH. Lesions of kidneys, liver and heart were the predominant pathological findings. Our own results are compared with those obtained by other authors who have investigated mice carrying rat, bovine or ovine growth hormone fusion genes. GH-transgenic mice may serve as a model system to investigate ectopic expression of hormone genes thus circumventing endogenous feedback control mechanisms in complex hormonal cascades.

Animals↗

Adverse effects of the antifertility agent DL 717-IT (Canocenta, Byk Gulden, FRG). Pathological findings in the rabbit.

The post-coital antifertility agent DL 717-IT (Canocenta, Byk Gulden, FRG) was administered to sixteen female (5 pregnant and 11 nonpregnant) New Zealand White (NZW) rabbits by single i.m. injections at a dose of 2.5 mg/kg body weight. The corresponding number of controls received the vehicle of the drug only. Pregnancy was interrupted in all the DL 717-IT-treated rabbits. Obvious loss of bodyweight (-15% at mean) was observed in all the test animals during the first two test weeks after treatment. Same sized groups of test and control animals were euthanasized 3, 4, 5, and 6 weeks after the initiation of the treatment and complete necropsies and histological examinations were performed. One of the test animals died on day 21. Pathological findings involved epidermal hyperplasia, hyper- and dyskeratosis seen in 16/16, zonal and massive liver necrosis in 8/16, generalized degeneration of the skeletal muscles in 6/16, and focal myocardial necrosis in 5/16 test animals. Vitamin A concentrations in liver tissue were found to be significantly reduced in the experimental animals compared to the controls. Consequently the skin lesions may possibly be explained as the result of reduced vitamin A synthesis due to DL 717-IT-induced hepatocellular damage. The results of this study indicate severe toxic effects of DL 717-IT in the given formulation in the rabbit at dosages reported to be well tolerated in several species and recommended for veterinary use to terminate unwanted pregnancies in the bitch.

Abortifacient Agents↗

[Effect of ventricular filling volume on the R-amplitude in the ECG].

Among others as cause of the sigma R-amplitude in the ECG changes of the ventricular filling and the stroke volume, respectively, the sympathetic tone and the coronary blood supply are discussed. Patients with absolute arrhythmia in atrial fibrillation as well as patients with extrasystoles represent model examples, in whom of the three factors mentioned above only the stroke volume is changed. Measurements of the sigma R-amplitude as well as of the Einthoven/Goldberger leads as well as of the Wilson leads on the same patient showed higher sigma R-values for the heart beats which were preceded by a short diastolic filling phase (rapid phase of the absolute arrhythmia, interpolated extrasystoles) than in the heart beats with previous long diastolic filling time (slow form of the absolute arrhythmia, extrasystole with compensatory interval). The findings considerably change in their size from patient to patient, however, they are statistically to be ascertained in their tendency. In the practical valuation deviations of the sigma R-amplitude values which do not correspond to this relation should be referred to other determinants of the R-amplitude.

Atrial Fibrillation↗

Attempts to localize the defect in dysgammaglobulinemia of UM-B19 chickens by studying the effect of immunomodulating substances on immunoglobulin and antibody production.

The extreme decreased levels of IgG in dysgammaglobulinemic UM-B19 chickens are linked with decreased antibody activity. Antibody activity to T-dependent (although diminished) and T-independent antigens is present but is restricted to IgM and IgA antibodies. Complete Freund's adjuvant enhances the existing isotype pattern of serum immunoglobulins and antibodies. The antibody response to a "T-independent" antigen (B. abortus) is greatly increased by CFA in dysgammaglobulinemic chickens. Beside the appearance of high levels of IgG in dysgammaglobulinemic chickens during the first weeks of life and in transitory dysgammaglobulinemia, remarkable IgG synthesis can be temporarily induced by the mitogenic activity of LPS and even more by the regulatory function of Levamisole. Furthermore, LPS and Levamisole induce IgG antibody synthesis to concomitantly administered antigen, the IgG antibodies appearing within the normal time. Contrary to a missing feedback inhibition from total IgG to IgM serum immunoglobulins, a feedback inhibition from IgG to IgM antibodies is found. No correlation can be found between Levamisole-induced IgG immunoglobulin concentrations, and IgG antibodies. Germfree rearing for one week or longer prevents the dysgammaglobulinemic defect. The following conclusions are drawn: Early antigenic stimulation seems to be the inducing factor for dysgammaglobulinemia in UM-B19 chickens. A BG cell pool is still present in adult dysgammaglobulinemic chickens. This BG cell pool is probably diminished to a varying extent. T cell helper functions seem to be present (albeit they may be disturbed) and can be stimulated. IgG specific T cell suppression is probable. From these conclusions the etiology of the dysgammaglobulinemia in UM-B19 chickens is hypothesized to be primarily due to delayed bursal development: Immature BG cells are eliminated by environmental antigens during the neonatal period in a process similar to tolerance induction. This event, in turn, induces suppressor mechanism(s) or disturbance in helper mechanism(s).

Adjuvants, Immunologic↗

[Occurrence and economic importance of congenital hernia in German Fleckvich calves].

The frequency of congenital hernia was investigated in German Fleckvieh calves being driven up for sale on livestock markets for breeding and fattening calves in Miesbach and Traunstein. Data were collected on 77 livestock auctions in the years 1996 and 1997. Altogether 53,105 calves were examined and 1.8% of these calves showed a congenital umbilical hernia. The incidence of umbilical hernia was significantly influenced by the sex of the calf, the occurrence of multiple births, the market place/market date, the sire and the sire line. Red Holstein blood proportion, lactation number, duration of pregnancy and 305 day milk performance were not of significant importance. Herd milk level did not influence the incidence of congenital umbilical hernia, however, herdmate averages for calves differed significantly in their incidence. The average difference of the market price between male calves affected by congenital umbilical hernia and not affected male calves amounted to 75 DM, in female calves, however, only to 38 DM. The risk, that a congenital umbilical hernia is not closing within an age of 15 months, depends on the width of the hernial opening in the newborn calf. An opening of 4 cm and more has only a healing chance of 50% and less. However, negative effects on fattening and carcass traits could be not found. The genetic influence on congenital umbilical hernia was obvious. The analyses indicated that the incidence of congenital umbilical hernia observed could not be explained by one autosomal recessive gene locus, but it seemed much more likely that more than one gene locus is involved or a mixed multifactorial monogenic mode of inheritance may be the underlying genetic mechanism. Breeders should be aware of the implications of congenital hernias and thus, congenital hernia should get more attention in the selection process of young sires.

Animals↗