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Biomedical subjects

W Zimmermann

Publications and source records attributed to W Zimmermann.

At least 145 records · Page 8Linked to original sources
PubMed1989

Analysis of the size of the carcinoembryonic antigen (CEA) gene family: isolation and sequencing of N-terminal domain exons.

Five members of the human CEA gene family [human pregnancy-specific beta 1-glycoprotein (PS beta G); hsCGM1, 2, 3 and 4] have been isolated and identified through sequencing the exons containing their N-terminal domains. Sequence comparisons with published data for CEA and related molecules reveal the existence of highly-conserved gene subgroups within the CEA family. Together with published data eleven CEA family members have so far been determined. Apart from the highly conserved coding sequences, these genes also show strong sequence conservation in their introns, indicating a duplication of whole gene units during the evolution of the CEA gene family.

Amino Acid Sequence↗
PubMed1989

Intra- and interspecies analyses of the carcinoembryonic antigen (CEA) gene family reveal independent evolution in primates and rodents.

Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.

Animals↗
PubMed1989

[Enzootic pneumonia (EP): the partial curing of EP-reinfected swine herds as an alternative to total cure].

Using a partial sanitation method "Enzootic Pneumonia" (EP) could be eradicated in 17 EP-reinfected pig breeding herds. Partial sanitation includes separation measures in form of a piglet and gilt free interval on one side and as an additional protection against reinfection the temporary feeding of a medicated diet on the other side. Frequent herd controls for several years as well as mixed fattening experiments with carcass examination combined with milk and blood serology served as criteria for the sanitation success. From these results it is concluded that the infection pathway of EP is mainly maintained by young animals in the herd. Contrary to total sanitation, which will amount to at least sFr. 720 per sow, partial sanitation will only cost between sFr. 40-170 per sow, depending on herd size. Therefore, partial sanitation may be regarded as a full alternative to total sanitation after an outbreak of EP.

Animals↗
PubMed1988

Chromosomal localization of the carcinoembryonic antigen gene family and differential expression in various tumors.

Carcinoembryonic antigen (CEA) is a glycoprotein which is important as a tumor marker for a number of human cancers. It is a member of a gene family comprising about 10 closely related genes. In order to characterize mRNAs transcribed from individual genes we have identified by DNA and RNA hybridization experiments, gene-specific sequences from the 3' noncoding regions of CEA, and of nonspecific cross-reacting antigen (NCA) mRNAs, which have been recently cloned. With these probes, CEA mRNAs with lengths of 3.5 and 3.0 kilobases and an NCA mRNA species of 2.5 kilobases were identified in various human tumors. A 2.2-kilobase mRNA species, however, could only be detected in leukocytes of patients with chronic myeloid leukemia by hybridization with a probe from the immunoglobulin-like repeat domain of CEA. This region is known to be very similar among the various members of the CEA gene family, and indeed the probe hybridizes with all four mRNA species. In situ hybridization with a cross-hybridizing probe from the NCA gene localized the members of the CEA gene family to the short and to the long arm of chromosome 19. In addition, a CEA cDNA probe was found to hybridize to the long arm of chromosome 19 only.

Antigens, Neoplasm↗
PubMed1988

tRNA-mediated labelling of proteins with biotin. A nonradioactive method for the detection of cell-free translation products.

We have developed a new method for the rapid and sensitive detection of cell-free translation products. Biotinylated lysine is incorporated into newly synthesized proteins by means of lysyl-tRNA that is modified in the epsilon-position. After electrophoresis in a dodecyl sulfate gel and blotting onto nitrocellulose, the translation products can be identified by probing with streptavidin and biotinylated alkaline phosphatase, followed by incubation with a chromogenic enzyme substrate. The non-radioactive labelling by biotin approaches in its sensitivity that obtained by radioactive amino acids. The products are absolutely stable and can be rapidly identified. The new method has been tested with different mRNAs in the cell-free translation systems of wheat germ and reticulocytes. Neither the interaction of secretory proteins with the signal recognition particle nor the in vitro translocation across the endoplasmic reticulum membrane or core glycosylation of nascent polypeptides are prevented by the incorporation of biotinylated lysine residues. The results indicate that both the ribosome and the endoplasmic reticulum membrane permit the passage of polypeptides carrying bulky groups attached to the amino acids (by atomic models it was estimated that the size of the side chain of lysine changes from approximately equal to 0.8 nm to approximately equal to 2 nm after modification.

Affinity Labels↗
PubMed1988

Characterization of a cDNA clone for the nonspecific cross-reacting antigen (NCA) and a comparison of NCA and carcinoembryonic antigen.

NCA (nonspecific cross-reacting antigen), a glycoprotein found in normal lung and spleen, is immunologically related to carcinoembryonic antigen (CEA), which is found in over 95% of colon adenocarcinomas. From a human genomic library, we previously cloned part of an NCA gene and showed that the amino-terminal region has extensive sequence homology to CEA (Thompson, J. A., Pande, H., Paxton, R. J., Shively, L., Padma, A., Simmer, R. L., Todd, Ch. W., Riggs, A. D., and Shively, J.E. (1987) Proc. Natl. Acad. Sci. U. S.A. 84, 2965-2969). We now present the nucleotide sequence of a cDNA clone, containing the entire coding region of NCA (clone 9). The clone was obtained from a lambda gt 10 library made from the colon carcinoma cell line SW 403; the clone contains a 34-amino acid leader sequence, 310 amino acids for the mature protein, and 1.4 kilobases of 3'-untranslated region of the NCA gene. A comparison of the NCA sequence to the CEA sequence (Oikawa, S., Nakazato, H., and Kosaki, G. (1987) Biochem. Biophys. Res. Commun. 142, 511-518; Zimmerman, W., Ortlieb, B., Friedrich, R., and von Kleist, S. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 2690-2694) shows that both proteins contain doublets of an immunoglobulin-like domain, of which there are one copy in NCA and three copies in CEA, a 108-amino acid amino-terminal domain with no cysteine residues, and a carboxyl-terminal hydrophobic domain of sufficient length to anchor the glycoproteins in the cell membrane. Overall, the corresponding coding regions possess 85% sequence homology at the amino acid level and 90% homology at the nucleotide level. Forty nucleotides 3' of their stop codons, the CEA and NCA cDNAs become dissimilar. The 108-amino acid amino-terminal region together with part of the leader peptide sequence corresponds exactly to a single exon described in our previous work. The data presented here further demonstrate the likelihood that CEA recently evolved from NCA by gene duplication, including two duplications of the immunoglobulin-like domain doublet of NCA.

Amino Acid Sequence↗
PubMed1988

Human beta-casomorphin-8 immunoreactive material in the plasma of women during pregnancy and after delivery.

A method for the extraction of human beta-casomorphin-8 immunoreactive material from human plasma and a radioimmunoassay for its determination in the plasma extracts were developed. Blood was collected from 34 men, from 35 non-pregnant women, from 35 pregnant women and from 138 women after delivery and plasma extracts were assayed for the presence of human beta-casomorphin-8 immunoreactive materials. No human beta-casomorphin-8 immunoreactive material was detected in the plasma of men or non-pregnant women, whereas such material was found in the plasma of 26 out of 35 pregnant women and in the plasma of 100 out of 138 women after parturition. Material collected from women after delivery was characterized by gel filtration and high-performance liquid chromatography (HPLC) and was found to be of different composition in various individuals; its components, one of which coeluted with human beta-casein from the HPLC column, have apparently higher molecular weights than human beta-casomorphin-8. Some of these compounds seem to be very stable against enzymatic degradation at 37 degrees C in human plasma, whereas human beta-casomorphin-8 proved to be degraded very fast under identical conditions. A physiological significance of mammary products of the beta-casomorphin type during pregnancy or after parturition is suggested.

Caseins↗
PubMed1988

The carcinoembryonic antigen gene family: structure, expression and evolution.

The molecular cloning of carcinoembryonic antigen (CEA) and several cross-reacting antigens reveals a basic domain structure for the whole family, which shows structural similarities to the immunoglobulin superfamily. The CEA family consists of approximately 10 genes which are localized in two clusters on chromosome 19. So far, mRNA species for five of these genes have been identified which show tissue variability in their transcriptional activity. Expression of some of these genes in heterologous systems has been achieved, allowing the localization of some epitopes. The characterization of a CEA gene family in the rat and a comparison with its human counterpart has been utilized in the development of an evolutionary model.

Amino Acid Sequence↗