Pyrrolizidine alkaloid poisoning in yaks. First report and confirmation by identification of sulphurbound pyrrolic metabolites of the alkaloids in preserved liver tissue.
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Biomedical subjects
Publications and source records attributed to H Winter.
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In a prospective, randomised trial bronchoscopy was performed either in local anaesthesia (LA) or general anaesthesia, each on 15 ventilated patients. LA was carried out with oxybuprocain-hydrochloride 1% in repeated doses injected into the trachea and main bronchi, general anaesthesia with midazolam, piritramide and vecuronium bromide. Measurements were performed before, 3 minutes after induction of anaesthesia, immediately after bronchoscopy and 15 and 60 minutes after bronchoscopy. There was no effect on cardiocirculatory function during bronchoscopy in both groups, but we found a decrease in paO2 from 97 to 80 mmHg (median) after application of LA. Subsequent bronchoscopy did not significantly influence paO2. The present study shows that in ventilation patients undergoing fibreoptic bronchoscopy, the application of LA will usually result in a decline of arterial oxygen tension. This procedure should therefore only be performed if general anaesthesia is undesirable, as e.g. in patients being weaned from ventilation.
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The foot sole epidermis of the fore and hind feet of the adult mouse contains an acidic (type I) mRNA-encoded 73-kDa keratin polypeptide which cannot be detected in any other skin site of the mouse integument. Western blot analysis using an antibody specific for the 64-kDa keratin 9 of human and bovine callus-forming epidermis [A. C. Knapp et al. (1986) J. Cell Biol. 103, 657-667] demonstrates that the 73-kDa keratin represents the murine analog of keratin 9 of man and cow. Concomitant investigations in two related rodent species indicate that the size of this keratin varies more among species than that of any other orthologous keratin. Histological examination of adult mouse foot sole skin reveals an extremely thick and undulated epidermis covering the apical portion of the six footpads, whereas the epidermal-dermal junction of the lateral walls of these nodular protuberances as well as that of the remainder of the foot sole skin is essentially flat. If sections of adult foot sole skin are investigated by indirect immunofluorescence with the keratin 9-specific antibody, intense cytoplasmic staining is restricted to the apical rete pegs of the footpad epidermis in which virtually all suprabasal cells express keratin 9. However, we also observed keratin 9-negative cell columns ascending straight above the tips of the dermal papillae and separating the keratin 9-positive rete pegs from each other. At the transition from the strongly undulated apical epidermis to the flat epidermis of the lateral walls of the footpads, keratin 9-positive cells loose their coherence and gradually disappear toward the inter-footpad epidermis. This intimate relationship between the morphogenesis of epidermal ridges and inter-ridges and the expression of keratin 9 is also visible in foot sole epidermis of neonatal mice. Here we observed the appearance of keratin 9-positive suprabasal cells concomitant with the onset of pronounced folding of the apical footpad epidermis by about Day 3 after birth. Our findings confirm the view that the expression of keratin 9 is characteristic of a highly specialized pathway of epidermal differentiation. We propose a hypothesis for keratin expression in skin sites which are subject to pronounced mechanical wear and tear.
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The ultrastructural feature of keratinocytes was investigated in human superficially spreading melanomas of type B. The tumor cells of these melanomas are characterized by spheroidal melanosomes and containing pheomelanins. Contrary to type A melanomas the keratinocytes show no striking transformation reaction neither in the nucleus nor in the cytoplasm although this part of the cell mostly contains abundant melanin granules surrounding the nucleus. Whether there exists a relation to the clinical course still has to be clarified.
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Specific keratin cDNA probes and monospecific antikeratin antisera were used to analyze mouse epidermis and epidermal tumors for the expression of a type I 47-kDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia. We demonstrated that this keratin was virtually absent from the entire body epidermis at various stages of development. Also, it was not detected in various forms of acute and chronic epidermal hyperproliferation or in epidermal cells cultured under conditions that favored either cell proliferation or in vitro differentiation. In contrast, K13 was consistently expressed in squamous cell carcinomas of the skin induced by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate (TPA), whereas papillomas obtained by the same two-stage protocol were distinctly heterogeneous with regard to the expression of this keratin. These findings were true for two different strains of mice (NMRI and Sencar). Papillomas collected from Sencar mice after 12 wk or from NMRI mice after 15 wk of promotion with TPA were either negative for K13 or elicited variable amounts of this keratin. In all cases of positive expression of K13 in tumors, as in normal stratified internal epithelia, both the keratin protein and its mRNA invariably occurred in the differentiating cell compartments. In contrast to what we found in internal stratified epithelia, however, K13 was expressed without its commonly encountered type II 57-kDa partner, K4. Papillomas negative for the K13 protein were also devoid of K13 transcripts. This indicates that the aberrant K13 expression in tumors is regulated at the level of transcription. Our results suggest that K13 may provide a marker for malignant conversion in the mouse two-stage skin carcinogenesis model and may be especially suited for studies of gene expression regulation.
The internal epithelium of mouse forestomach represents a fully keratinized tissue that has many morphological aspects in common with the integumental epidermis. In the present study we have, therefore, analyzed keratin expression in the total epithelium, in subfractions of basal cells and in living and dead suprabasal cells that were obtained by Percoll density gradient centrifugation of trypsin-dissociated forestomach keratinocytes. The keratin analysis revealed that basal forestomach keratinocytes synthesize the same keratin types as basal epidermal cells (60000, 52,000 and 47,000 daltons), whereas differentiating cells contain both the epidermal suprabasal keratin pair (67,000 and 59,000 daltons) and the suprabasal keratin pair characteristic for other internal squamous epithelia (57,000 and 47,000 daltons). Indirect immunofluorescence using an antibody recognizing the members of the epidermal-type suprabasal keratin pair and in-situ-hybridization experiments using specific cDNA probes for the members of the internal-type keratin pair showed that the two keratin pairs are uniformly coexpressed in living suprabasal forestomach keratinocytes. Furthermore, it could be shown that distinct cells in the basal cell layer acquire the ability to express both the 67,000/59,000 dalton and the 57,000/47,000 dalton keratin pair and that some basal cells apparently lose the ability to synthesize mRNAs for basal keratins.
The aim of this paper was to demonstrate the efficiency of partial splenic resection in treatment of chronic idiopathic thrombocytepenie purpura (Werlhof-Disease). In all but one case remissions of thrombocyte counts over 100 Gpt/l could be achieved. Immunological studies demonstrate the existence of a suppressor-state after this operation, which could be responsible for success of this procedure. In contrast to general considerations the partial-splenectomized child must be considered as an immunological deficient organism for about 6 to 12 months. Restoration of immunological-means whole splenic functions-parameters is to expect always after this time.
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Cytogenetic studies of the mithun (Bos frontalis), the siri (Bos indicus) and their hybrids, as well as histological examinations of testes and epididymis of siri and hybrids were undertaken to throw further light on male hybrid infertility and interspecies incompatibility, in order to facilitate the possible development of a stable interspecies crossbreed which would be similar to the highly profitable jatsum, the female mithun cross siri hybrid. In both species there are distinct centromeric heteromorphisms which should provide a rich source of genetic markers for tracing chromosomes in controlled hybrid programmes. The nucleolar organisers in the F1 hybrids were derived from both parents, in contrast to other interspecies hybrids where the nucleolar organisers of one species tend to be suppressed by the other. This indicates a relatively close relationship between mithun and siri and supports the prospect of success for developing a stable crossbreed. Transferrins which may also be a useful source of genetic markers were identified and differences between siris and mithuns noted, especially in the D-bands. No A-bands were found in the siris and no E-bands in the mithuns. Whether this is a breed or species characteristic will have to be confirmed by examination of more animals. The findings on blood groups and haemoglobins, including differences between the two species, were similar to results obtained previously. In meiosis the sex vesicles were intact which indicates that infertility and incompatibility factors should be located in autosomes. In cytogenetic and histological examinations the testes of the siris were comparable to those of European cattle, while in all hybrids spermatogenetic activity was deficient although there were great differences between and within generations. While the exact mechanism of this diversity is not known at this stage, it should make it possible to select for increased male hybrid fertility which would be a prerequisite for developing a stable interspecies crossbreed. This selection would be facilitated by correlating infertility and incompatibility with genetic profiles and markers. A mithun cross siri crossbreed would also serve as a model for other interspecies breeding.
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We have constructed cDNA libraries with poly(A)+ RNA from normal mouse footpad epidermis and from a squamous cell carcinoma of mouse back skin. Both libraries were screened for type I keratin clones. We present sequence data of three keratin cDNA clones which selected mRNAs coding for two 52-kDa proteins (clones pke 52 and pkSCC 52) as well as for a 50-kDa protein (clone pkSCC50). According to their carboxyl-terminal sequences, the two 52-kDa keratin proteins belong to a group of keratins with serine-rich subdomains adjacent to the alpha-helix, whereas the short carboxyl-terminus of the 50-kDa protein lacks a distinct substructure. Sequentially the two 52-kDa keratins are more closely related to each other than to any other mouse type I keratin. However, in situ hybridization with specific subclones reveals a distinctly different pattern of expression in mouse epithelia. Clone pkSCC 52 contains sequence information for a 52-kDa keratin present in basal cells of epidermis and other stratified epithelia, whereas the pke 52 cDNA encodes a keratin which is predominantly expressed in suprabasal cells of nonepidermal tissues. In terms of nucleotide sequence identities, it cannot precisely be decided which of the two mouse 52-kDa proteins is the equivalent of the human epidermal 50-kDa keratin protein (Hanukoglu, I., and Fuchs, E. (1982) Cell 31, 243-252). In the case of the bovine keratin VII, however (Jorcano, J.L., Rieger, M., Franz, J.K., Schiller, D.L., Moll, R., and Franke, W.W. (1984) J. Mol. Biol. 179, 257-281) the sequence identity values speak for an equivalence with the mouse ke 52 keratin. Obviously, in situ hybridization experiments would best be suited to unravel the precise interspecies relationship between the four highly similar keratins. The discriminatory efficacy of this technique is further emphasized by the demonstration that the mRNA for a 50-kDa keratin is present not only in hyperproliferative epithelia, but also in normal cells of hair follicles.
Cocaine was administered as 1-, 2-, and 4-mg/kg intravenous bolus doses to each of six sheep. Plasma samples were collected as a function of time and assayed for cocaine using reversed-phase ion-pair HPLC. The assay involved double extraction with ether and UV detection at 229 nm. Using 2 mL of plasma, levels of 1 ng/mL of cocaine can be measured. The concentration versus time data obtained for the plasma samples were analyzed by a "noncompartmental" method. The pharmacokinetic parameters of cocaine in sheep had mean values of 4.0 L/kg, 3.5 L/kg, and 0.29 L X min-1 X kg-1 for Vd, Vdss, and CL respectively. The clearance of cocaine in sheep was much higher than cardiac output. Pulmonary first-pass effect has been suggested as the possible explanation for the large clearance of cocaine in sheep.