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Biomedical subjects

G Peters

Publications and source records attributed to G Peters.

At least 217 records · Page 12Linked to original sources
PubMed1990

Gene amplification on chromosome band 11q13 and oestrogen receptor status in breast cancer.

We have analysed DNA from 183 primary breast cancers for amplification or rearrangement of a number of cellular proto-oncogenes, focusing primarily on a cluster of markers on the long arm of chromosome 11. Two of these oncogenes, INT2 and HST1, both of which encode members of the fibroblast growth factor family, are implicated in the generation of virally induced mammary tumours in mice. Here we confirm earlier reports that the q13 region of chromosome 11, in which these genes are tandemly linked, is modestly amplified in approximately 15% of primary human breast cancers. This amplification is confined, with one exception, to cases in which the oestrogen receptor (ER) levels are in excess of 20 fmol/mg protein (P = 0.001). However, DNA amplification does not usually result in detectable expression of either the INT2 or HST1 gene. The data imply that some other gene in the vicinity must contribute to the development of a subset of ER-positive tumours and that assessing the amplification of this region of DNA may be of value in defining a separate category of ER-positive tumour.

Adult↗
PubMed1990

Comparative study on the macrolides erythromycin and clarithromycin: antibacterial activity and influence on immune responses.

The in vitro activity of erythromycin and clarithromycin (a new macrolide antibiotic) on clinical bacterial isolates as well as their effects on the cellular and humoral immune responses in BALB/c-mice and on human granulocytes/monocytes was investigated. Treatment of BALB/c-mice for 7 days with these drugs did not influence the delayed type hypersensitivity to oxazolone nor the production of IgG and IgM immunoglobulins. In vitro, exposure of granulocytes to erythromycin resulted in increased phagocytosis only in higher concentrations (20 mcg/ml), whereas clarithromycin enhanced chemiluminescence response of granulocytes in concentrations ranging from 2.5-20 mcg/ml. Subinhibitory concentrations of both substances modified Staphylococcus aureus and made them more susceptible for granulocyte phagocytosis.

Animals↗
PubMed1990

Antiphagocytic effect of the capsule of Staphylococcus simulans.

An encapsulated strain of Staphylococcus simulans was observed to be more resistant to phagocytosis by human granulocytes than was a nonencapsulated strain. Phagocytosis of the encapsulated strain was enhanced by antisera to S. simulans, but opsonic activity of antisera was removed by absorption with S. simulans capsular material. The encapsulated strain of S. simulans was also more invasive than the nonencapsulated S. simulans in vivo. More encapsulated than nonencapsulated S. simulans were found in heart blood when equal numbers of organisms were injected intraperitoneally into mice. Invasion of the bloodstreams of mice by encapsulated S. simulans was prevented by passive immunization (rabbit antiserum). Thus, the capsule of S. simulans inhibited phagocytosis in vitro and contributed to virulence in vivo.

Animals↗
PubMed1990

Proviral insertions within the int-2 gene can generate multiple anomalous transcripts but leave the protein-coding domain intact.

We examined the effects of mouse mammary tumor virus integration on the multiple RNA transcripts expressed from the int-2 proto-oncogene in virally induced breast tumors. Proviral insertion either upstream or downstream of the gene could simultaneously activate transcription from three dissimilar int-2 promoters. In some tumors, the activating provirus lies within the transcription unit and disrupts the structures of the various RNAs. Insertions in the 5' region of the gene had complex effects depending on the orientation and position of the provirus relative to the three promoters and intron-exon boundaries. RNase protection experiments identified transcripts initiated in the viral long terminal repeat, at normal and cryptic sites in the int-2 sequences, and from cryptic promoters in an inverted provirus. AT the 3' end, insertions occurred within the untranslated trailer and provided alternative termination signals that substituted for one or both of the normal the poly(A) addition sites. However, in no instance, of the 20 tumors analyzed in detail, did a provirus perturb the presumed open reading frame of the gene. These data strongly implicate the normal product of the int-2 gene, which is related to the fibroblast growth factor family, as a contributory factor in virally induced mammary tumors.

Animals↗
PubMed1990

Characterization of int-2: a member of the fibroblast growth factor family.

int-2 was discovered as a proto-oncogene transcriptionally activated by MMTV proviral insertion during mammary tumorigenesis in the mouse. Sequence analysis showed int-2 to be a member of the fibroblast growth factor family of genes. In normal breast and most other adult mouse tissues, int-2 expression was not detected except for low levels in brain and testis. However, using in situ hybridization, expression was found at a number of sites during embryonic development, from day 7 until birth. An analysis of the int-2 transcripts found in embryonal carcinoma cells revealed six major classes of RNA initiating at three promoters and terminating at either of two polyadenylation sites. Despite the transcriptional complexities, all size classes of RNA encompass the same open reading frame. Using an SV40 early promoter to drive transcription of an int-2 cDNA in COS-1 cells, several proteins were observed. These were shown to be generated by initiation from either of two codons: One, a CUG, leads to a product which localizes extensively to the cell nucleus and partially to the secretory pathway. In contrast, initiation at a downstream AUG codon results in quantitative translocation across the endoplasmic reticulum and the accumulation of products ranging in size from 27.5 x 10(3) Mr to 31.5 x 10(3) Mr in organelles of the secretory pathway. These proteins represented glycosylated and non-glycosylated forms of the same primary product with or without the signal peptide removed. These findings suggest the potential for a dual role of int-2; an autocrine function acting at the cell nucleus, and a possible paracrine action through a secreted product.

Amino Acid Sequence↗
PubMed1990

The mouse int-2 gene exhibits basic fibroblast growth factor activity in a basic fibroblast growth factor-responsive cell line.

The int-2 protein is related to basic fibroblast growth factor (bFGF) by amino acid sequence homology. To assess its biological activity, we constructed retroviral vectors containing four variants of mouse int-2 complementary DNA under the transcriptional control of the beta-actin promoter and tested their effects on human SW13 adrenal cortical tumor cells. This cell line specifically requires bFGF, interleukin 1, or transforming growth factor e for anchorage-independent growth in soft agar. Despite encoding a signal sequence that should direct the protein to the secretory pathway, vectors containing unmodified int-2 complementary DNA, or a form optimized for translation initiation at the AUG codon, were incapable of inducing SW13 growth in soft agar. However, SW13 transfectants expressing a construct (pSP1), in which a mouse immunoglobulin signal peptide sequence is linked to the int-2 coding sequences, grew well in soft agar. The concentrated conditioned medium from these pSP1-transfected cells supported anchorage-independent growth of SW13 indicator cells and competed with bFGF for binding to receptors. Western blot analysis with an int-2-specific antiserum detected Mr 30,000-32,000 int-2 products in cell extracts and conditioned medium from pSP1-transfected clones, whereas the conditioned medium from these and other SW13 clones contained only low levels of bFGF as measured in a specific radioimmunoassay. These data suggest that the product of the int-2 gene can functionally replace bFGF in modulating the anchorage-independent growth of SW13 cells.

Amino Acid Sequence↗
PubMed1990

[Animal welfare problems in the mass raising of commercial fish].

The maintainance of commercial fish cultures is regulated by Section 2 of the Animal Protection Laws, which require, among other things, that animals be kept under conditions where they can express normal behaviour and are not harmed by the culture methods. The welfare and health of the commercial fishes are largely dependent on the aquatic milieu, which is an extremely sensitive combination of chemical, physical and biological factors in intensive culture facilities. Disturbances of the equilibrium of these factors result in such problems as behavioural changes, increased susceptibility to infections and chronic health damage. The last of these problems is an unequivocal criterion for judging the conditions of captivity as unsuitable for the species. The widespread occurrence of chronic lesions in commercial facilities raises the question of whether mass culture of fishes that have scarcely been domesticated can in any way be interpreted as meeting the precepts of the Animal Protection Law as it is presently worded.

Animal Welfare↗
PubMed1989

The mouse homologue of hst/k-FGF: sequence, genome organization and location relative to int-2.

We have located and sequenced the murine homologue of the hst/k-FGF oncogene in genomic DNA clones that extend 3' from int-2 on mouse chromosome 7. The two genes are in the same transcriptional orientation, less than 20 kilobase pairs (kb) apart, and presumably evolved by tandem duplication of a common ancestral gene. RNase mapping and primer extension analyses indicated that the major 3.2 kb hst transcript expressed in undifferentiated embryonal carcinoma (EC) cell lines initiates at a unique cap site downstream from an obvious TATA-box. The 3' end of the transcript as identified in multiple cDNA clones occurs at an appropriate distance from a variant polyadenylation signal, ATTAAA. Translation of the major open reading frame would yield a 202 amino acid protein that is 82% homologous to human HST but lacking 4 residues at the presumed signal peptide cleavage site.

Amino Acid Sequence↗
PubMed1989

Vessel dilator cricothyrotomy for transtracheal jet ventilation.

Needle cricothyrotomy is a safe, relatively easy procedure and has been described to enable pulmonary ventilation for patients in both elective and emergency situations. Conventional IV cannulae are short, thin-walled, and easily kinked and, therefore, do not provide a secure system to jet oxygen into the trachea. The vessel dilators of most 7-9 French introducer kits are firm, pliable, resist kinking, and can be passed easily into the tracheal lumen. We describe our experience with the use of vessel dilator cricothyrotomy to oxygenate and ventilate the lungs of patients in emergency and elective situations.

Catheterization↗
PubMed1989

The structure and function of the int-2 oncogene.

The classification of int-2 as a growth factor is based primarily on the similarities between the predicted amino acid sequence and that of basic fibroblast growth factor (bFGF), as well as other members of this expanding family of related proteins. In this review, we summarise the background to the identification of int-2 as a proto-oncogene in virally induced mouse mammary tumours and describe key features of the structure and expression of both the mouse and human homologues. The normal sites of int-2 expression include specific embryonic cell types suggesting multiple inductive or morphogenetic roles. Recent progress in the characterisation of the int-2 product will be discussed in relation to the similarities and differences between int-2 and other FGFs.

Amino Acid Sequence↗
PubMed1989

The mouse homolog of the hst/k-FGF gene is adjacent to int-2 and is activated by proviral insertion in some virally induced mammary tumors.

The fibroblast growth factor-related protooncogenes, int-2 and hst/k-FGF, are within 17 kilobase pairs of one another on mouse chromosome 7 and are in the same transcriptional orientation. Approximately 70% of tumors induced in BR6 mice by mouse mammary tumor virus have proviral insertions adjacent to the int-2 gene. We find that the murine homolog of the hst/k-FGF gene can also be transcriptionally activated by the insertion of mouse mammary tumor virus DNA either upstream or downstream of the gene. In most tumors, only one of these adjacent genes is activated, but in some cases both genes are expressed. One of the hst-expressing tumors also has a virally activated int-3 gene. At least five distinct cellular genes (int-1, -2, -3, -4, and hst/k-FGF) can therefore contribute, either singly or in concert, to the development of histologically indistinguishable mammary tumors in mice infected by mouse mammary tumor virus.

Animals↗
PubMed1989

A putative int domain for mouse mammary tumor virus on mouse chromosome 7 is a 5' extension of int-2.

We extended the physical map of the mouse int-2 locus by demonstrating that the site of insertion for mouse mammary tumor virus DNA in plaque-type mammary tumors of GR mice is directly linked to int-2. An additional example of proviral integration is described in which a provirus in a presumed enhancer-insertion mode 15 kilobases upstream of the int-2 promoters is capable of activating expression of the gene at levels typical of other virally induced mammary tumors.

Animals↗
PubMed1989

Detection and characterization of the fibroblast growth factor-related oncoprotein INT-2.

Products of the fibroblast growth factor-related proto-oncogene int-2 have been detected by using a monoclonal antibody and polyclonal antisera raised against synthetic peptides predicted from the DNA sequence. COS-1 monkey cells transfected with int-2 DNA linked to the simian virus 40 early promoter contained at least four int-2-specific proteins, presumably representing modified forms of the expected 27-kilodalton primary translation product. The level of expression was increased approximately six- to eightfold by mutation of sequences around the presumed initiation codon, negating their capacity to encode a short oligopeptide in the +1 reading frame. Both tunicamycin inhibition and in vitro translation experiments indicated that some of the modifications correspond to asparagine-linked glycosylation, for which the sequence predicts a single site. In line with the similarities between INT-2 and other fibroblast growth factors, the in vitro translation products functioned as weak mitogens for mammary epithelial cells.

Amino Acid Sequence↗
PubMed1989

New aspects in the pathogenesis and prevention of polymer-associated foreign-body infections caused by coagulase-negative staphylococci.

The significance of polymer-associated infections caused by coagulase-negative staphylococci is discussed. The aspects of bacterial adhesion to polymeric materials as the first important pathogenetic step in the development of such infections are treated. The role of extracellular slime substance (ESS) produced by the bacteria in the pathogenesis is elucidated and newer results concerning the interference of ESS with host defense mechanisms and antibiotic therapy are presented. As an approach to the prevention of polymer-associated foreign-body infections, the modification of the polymeric materials is introduced. Results of recent studies to achieve antiadhesive materials by radiation modification of polymers as well as the development of antimicrobial surfaces by incorporating or bonding antibiotics to polymers are presented.

Bacterial Adhesion↗
PubMed1989

Sequence organization of the human int-2 gene and its expression in teratocarcinoma cells.

We report the genomic organization and DNA sequence of the human homologue of int-2, a proto-oncogene implicated in virally induced mammary tumours in the mouse, and expressed at specific sites and times during embryogenesis. Direct comparisons with the coding domains of mouse int-2 allowed us to delineate the intron-exon boundaries of the human gene. These boundaries were subsequently confirmed by ribonuclease protection analyses of the single 1.7 kilobase (kb) int-2 transcript detectable in the human teratocarcinoma cell line, Tera-2. The data suggest that human int-2 may also function in embryonic lineages but that its transcription may be less complex than in the mouse. The predicted human protein comprises 239 amino acids and is 89% homologous to its murine counterpart, except at the carboxy terminus. This divergence occurs distal to the region of int-2 that shows homology to other members of the FGF family of growth modulators and oncogenes.

Amino Acid Sequence↗
PubMed1989

[Topography and mechanisms of adhesion of uropathogenic Escherichia coli bacteria in the human kidney and renal pelvis].

The occurrence and significance of bacterial carbohydrate recognition proteins (bacterial lectins) and endogenous carbohydrate binding proteins (endogenous lectins) of human urothelium as well as kidney tubulus epithelium was analyzed with respect to the adhesion of urotoxogenic Escherichia coli bacteria. Using biotinylated neoglycoproteins, we demonstrated a wide spectrum of endogenous lectins with Galactose-, Mannose-, Fucose-, N-Acetylgalactosamine-, and N-Acetylglucosamine binding activities in the urothelium. In the kidney the distal nephron and especially the medullar collecting ducts exhibited a similar spectrum of endogenous carbohydrate binding activities as detected for the urothelium. Adhesion- as well as inhibition-experiments with selective blocking of either bacterial lectins or endogenous lectins of the target cells by different carbohydrates both reduced the bacterial adhesion. However, maximal inhibition of bacterial adhesion was achieved by simultanous blocking of microbial and target cell lectins with mannose or mannan. From these results it is reasonable to conclude that specific adhesion which may result in an organotropism (urotropism) of E. coli infection is due to a dual recognition mechanism which is accomplished by the combined interaction of the bachterial and host cell lectins with the corresponding carbohydrates of E. coli and that of the target cells respectively. Further studies showed that normal human serum possesses natural antiadhesins which are represented by the glycan parts of the serum-glycoproteins.

Bacterial Adhesion↗