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Biomedical subjects

G Peters

Publications and source records attributed to G Peters.

At least 181 records · Page 10Linked to original sources
PubMed1993

FGF3 from Xenopus laevis.

Fibroblast growth factor 3 (FGF3) was first identified as the product of a cellular oncogene activated by mouse mammary tumour virus but its normal role appears to be in the developing embryo. To gain further insights into its function, we have isolated sequences encoding the FGF3 homologue in Xenopus laevis, XFGF3. COS-1 cells transfected with XFGF3 cDNA express a 31 kDa product, p31, generated by signal peptide cleavage and Asn-linked glycosylation at the single consensus site. This product is secreted and becomes associated with the cell surface and extracellular matrix. Proteolytic cleavage of p31 in the extracellular compartment results in an amino-terminally truncated product, p27, that is also glycosylated. Both p31 and p27 bind quantitatively to heparin-Sepharose and can be displaced from the cell surface and extracellular matrix by soluble heparin. Conditioned medium containing these two proteins is capable of inducing transient morphological transformation of NIH3T3 cells and of stimulating DNA synthesis in quiescent C57MG and BALB/MK cells which express different isoforms of FGF receptors 1 and 2. Since XFGF3 behaves very differently from its mouse counterpart, we constructed chimeras in which amino-terminal sequences from XFGF3 were fused with carboxy-terminal sequences from mouse FGF3. Increasing the contribution from mouse FGF3 led to a more restricted host range for the chimeric ligand.

Amino Acid Sequence↗
PubMed1993

Activation of both Wnt-1 and Fgf-3 by insertion of mouse mammary tumor virus downstream in the reverse orientation: a reappraisal of the enhancer insertion model.

In retrovirus-induced tumors, proviral DNA is commonly found next to or within a cellular proto-oncogene such that transcription of the gene is influenced by the viral promoter or enhancer. Extensive surveys of naturally occurring tumors reveal that proviruses integrated on the 3' side of the gene are usually in the same transcriptional orientation, suggesting a model in which the bidirectional viral enhancer acts primarily on the closest promoters. Here we describe a virally induced mammary tumor that appears to contradict these ideas since the Wnt-1/int-1 and Fgf-3/int-2 proto-oncogenes have both been activated by mouse mammary tumor virus (MMTV) DNA integrated 3' of the gene in the opposite transcriptional orientation. However, by cloning the relevant DNAs, we show that these are not simple proviral insertions. In the Wnt-1 locus, there is an additional LTR immediately adjacent to the 3' end of the MMTV provirus, while in Fgf-3, the provirus has sustained a deletion that removes the 5' LTR, gag, and most of pol. These structural alterations can be reconciled with the enhancer insertion model by postulating that the viral enhancer can only function if it is not transcribed.

Animals↗
PubMed1993

[The prececal digestibility of corn, sunflower, cottonseed, linseed and soybean extract meal in swine with ileocecal anastomoses].

Five pigs were each surgically prepared with end-to-side (E.t.S.) and end-to-end (E.t.E.) ileorectal anastomoses (IRA). The ileo-caecal valve was preserved in both modifications. The animals were fed diets with maize or solvent extracted oil seed meals from sunflower, cottonseed, linseed or soybean and maize in combination with one of these oil seed meals. The aim of the experiment was to estimate the influence of both IRA-techniques on the precaecal nutrient digestibility and amino acid (AA) absorption. The crude carbohydrate digestibility in two of the five single protein diets and in three of the four blends were significantly higher in the E.t.S.--than in the E.t.E.--IRA group. There were no significant differences between the two IRA-modifications in crude protein (CP) and crude fat digestibility. No differences were observed in AA absorption for the single components maize, sunflower- and cottonseed meal. The absorption values of isoleucine, leucine and valine from linseed meal were significantly more than 5%-units higher in the E.t.S.-group than in E.t.E.-animals. There were similar results in soybean meal for four essential AA but with differences below 5%-units. Accordingly the two IRA-modifications did not influence the AA absorption to a practically important extent.

Amino Acids↗
PubMed1993

Foreign body associated infection.

One of the major complications associated with the use of medical devices and implants is foreign body associated infection. Its significance in modern medicine and its pathogenesis are discussed. Adherence to and colonization of a foreign body material and the interference of microbial products with the host defence are critical steps leading to foreign body infections. Therapy is difficult and hence the immediate administration of antibiotics and the removal of an infected device or implant is still preferred. New strategies for the prevention of foreign body infections are briefly introduced.

Anti-Bacterial Agents↗
PubMed1993

Retention of fibroblast growth factor 3 in the Golgi complex may regulate its export from cells.

The fibroblast growth factors (FGFs) fall into two distinct groups with respect to their mode of release from cells. Whereas FGF1 and FGF2 lack conventional signal peptides, the remaining members have typical features of secreted proteins. However, the behavior of mouse FGF3 is anomalous, since, despite entering the secretory pathway and undergoing primary glycosylation, its release from transfected COS-1 cells is very inefficient compared with that of FGF4 and FGF5. To investigate the unusual properties of FGF3, we analyzed the processing, secretion, and intracellular localization of a series of site-directed mutants as well as chimeras produced by fusing parts of FGF3, FGF4, and FGF5. Wild-type FGF3 was shown to accumulate in an immature form in the Golgi complex, from where it is slowly released into the extracellular matrix. Removing or relocating the Asn-linked glycosylation site further impaired its release, and exchanging the signal peptide or carboxy terminus had little effect. In contrast, a chimeric protein with an amino terminus from FGF5 was efficiently secreted and biologically active in cell transformation assays. The data suggest that a structural feature of FGF3 involving the amino-terminal region and glycosylation site has a significant bearing on its passage through the Golgi complex and may regulate the secretion of the ligand.

3T3 Cells↗
PubMed1993

Chromosome 11q13 abnormalities in human breast cancer.

Amplification of markers centred on band q13 of human chromosome 11 is a consistent feature in a subset of oestrogen receptor positive breast cancers. Although the amplification was initially scored via FGF3/INT2, which has strong credentials as a mammary oncogene, current data suggest that some other gene on 11q13 provides the driving force for amplification. Here we have reviewed our understanding of the amplified DNA, the genes it encompasses and the evidence in favour of two candidate oncogenes, CCND1 and EMS1. As well as being among the most frequently amplified markers in the region, these genes are expressed at elevated levels as a consequence of amplification, and their predicted functions would be consistent with a role in tumorigenesis. Irrespective of the final conclusions regarding their biological relevance, the overexpression of CCND1 or EMS1 should provide a more amenable assay for the amplification and help to clarify its clinical significance.

Animals↗
PubMed1993

Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell lines.

The cyclin D1 gene can be transcriptionally activated in lymphoid tumours as a result of chromosomal rearrangements but is normally silent in B and T lymphocytes. By isolating cyclin D1-related cDNAs from a B-lymphoid cell line, we identified clones that contain the coding sequences of human cyclin D2. The predicted 289 amino acid protein shares 63% identity with human cyclin D1. Although cyclin D2 transcripts were detected in many lymphoid cell lines, it was not ubiquitously expressed and there was no apparent correlation with cyclin D1 levels. For example, two B-cell leukaemia lines, JVM-2 and Karpas 620, both of which have 11q13 translocations and express cyclin D1, contained markedly different amounts of cyclin D2. An obvious distinction between these cells is that the JVM-2 line, which expresses high levels of cyclin D2, was immortalized by Epstein-Barr virus (EBV). We subsequently found that cyclin D2 is consistently expressed in group III Burkitt's lymphoma (BL) and in lymphoblastoid cell lines immortalized by EBV, but not in group I BLs, in which expression of the EBV genome is more restricted. The data imply that the D-type cyclins may have non-overlapping functions at specific stages of lymphocyte differentiation and that the expression of cyclin D2 may be influenced, directly or indirectly, by EBV.

Amino Acid Sequence↗
PubMed1992

Linkage map of a region of human chromosome band 11q13 amplified in breast and squamous cell tumors.

DNA amplification involving markers on human chromosome band 11q13 is a consistent feature of several major cancers, notably adenocarcinoma of the breast and squamous cell carcinoma of the head, neck, lung, and esophagus. Since the presence of the amplification may be clinically significant, by defining a subset of patients at increased risk, it is important to establish which of the several genes on the amplified DNA provides the selective force. Here we describe a physical map of the centromeric end of the amplified DNA as it exists in a particular squamous carcinoma cell line (UMSCC2) and establish an unambiguous order for several known markers in the region, including pMS51/D11S97, pHB159/D11S146, BCL1, PRAD1/D11S287, HSTF1/FGF4 and INT2/FGF3. Significantly, PRAD1 is within 120-150 kb of the BCL1 translocation breakpoint and the data identify a new CpG island (D11S814) between PRAD1 and HSTF1. The ordering of the HSTF1 and INT2 genes and the clustering of CpG islands in the region have important implications in assessing whether the frequently observed amplifications at 11q13 are centered on one or more genes.

Adenocarcinoma↗
PubMed1992

Left ventricular ejection fraction is increased during transesophageal echocardiography in patients with impaired ventricular function.

Transesophageal echocardiography (TEE) is increasingly being used to assess left ventricular function (LVF). However, little data exist on the quantitative accuracy of this technique and its influence on LVF. Thus 50 ambulatory adult patients (mean age 62 +/- 15 years) were studied with transthoracic echocardiography (TTE) immediately before, before the end, and 10 minutes after TEE. Left ventricular ejection fraction (LVEF) was calculated using the modified Simpson's method. In subjects (n = 24) with impaired LVF (LVEF less than 55% by TTE), TTE-derived LVEF increased from 37 +/- 13% to 45 +/- 15% (p less than 0.001) during TEE. In 13 of 24 subjects with abnormal LVF, LVEF significantly increased during TEE as defined by an increase in LVEF by at least 5 ejection fraction units. In four of these subjects LVF normalized during TEE. LVEF was unchanged during and after TEE in the subjects (n = 26) with normal LVF (LVEF greater than 55%). An excellent correlation was found between LVEF derived by TEE and that derived by TTE performed during TEE (r = 0.93, SEE = 6.6%, p less than 0.001). LVEF determined by TEE compared well with that derived by TTE and should be a useful measure of global left ventricular function. However, an increase in LVEF during TEE occurs in over 50% of patients with impaired LVF and may be important to consider in individual subjects.

Adult↗
PubMed1992

In-vitro efficacy of a central venous catheter ('Hydrocath') loaded with teicoplanin to prevent bacterial colonization.

A technique is described by which a central venous catheter ('Hydrocath') is loaded with the glycopeptide teicoplanin for the prevention of catheter infection. Catheters are immersed in teicoplanin solution and, due to the hydrophilic surface coating of the 'Hydrocath' catheter, teicoplanin is absorbed by the surface layer. The catheter loading is influenced by the experimental conditions and is assessed by measuring teicoplanin elution from the catheter using a bioassay. Increasing the antibiotic concentration, incubation time and temperature leads to the binding of higher amounts of teicoplanin to the catheter, resulting in a higher teicoplanin release from the catheter. Experiments on in-vitro bacterial adherence to teicoplanin-loaded and unloaded catheters reveal that the initial bacterial adhesion is not prevented. However, in the case of the teicoplanin-loaded catheter initially adherent bacteria are eliminated from the catheter surface, thus preventing catheter colonization by bacteria for at least 48 h. Such loaded catheters could be suitable for inhibiting early-onset, catheter-related infections.

Bacterial Adhesion↗
PubMed1992

In-vitro efficacy of a central venous catheter complexed with iodine to prevent bacterial colonization.

Infections of central venous lines are still a problem in daily medicine. Despite adequate antibiotic therapy, removal of an infected catheter often becomes necessary. A simple procedure has been developed by which a special hydrophilic central venous catheter (Secalon-Hydrocath) can be loaded with iodine. Iodine is complexed in the hydrophilic polyvinylpyrrolidone surface coating of the Hydrocath catheter and is released during contact with an aqueous medium. The amount of complexed iodine depends on the incubation time in Lugol's solution. Antimicrobial activity of the loaded catheters was assessed with Staphylococcus epidermidis, showing complete inhibition of bacterial adherence to the catheters for the duration of iodine release. Depending on the experimental conditions, iodine released from the catheter is also active on bacteria in the surrounding medium.

Bacterial Adhesion↗
PubMed1992

Developmental expression of the Xenopus int-2 (FGF-3) gene: activation by mesodermal and neural induction.

We have used a probe specific for the Xenopus homologue of the mammalian proto-oncogene int-2 (FGF-3) to examine the temporal and spatial expression pattern of the gene during Xenopus development. int-2 is expressed from just before the onset of gastrulation through to prelarval stages. In the early gastrula, it is expressed around the blastopore lip. This is maintained in the posterior third of the prospective mesoderm and neuroectoderm in the neurula. A second expression domain in the anterior third of the neuroectoderm alone appears in the late gastrula, which later resolves into the optic vesicles, hypothalamus and midbrain-hindbrain junction region. Further domains of expression arise in tailbud to prelarval embryos, including the stomodeal mesenchyme, the endoderm of the pharyngeal pouches and the cranial ganglia flanking the otocyst. It is shown, by treatment of blastula ectoderm with bFGF and activin, that int-2 can be expressed in response to mesoderm induction. By heterotypic grafting of gastrula ectoderm into axolotl neural plate, we have also demonstrated that int-2 can be expressed in response to neural induction. These results suggest that int-2 has multiple functions in development, including an early role in patterning of the anteroposterior body axis and a later role in the development of the tail, brain-derived structures and other epithelia.

Amino Acid Sequence↗
PubMed1992

Nonuniform expression of a mouse mammary tumor virus-driven int-2/Fgf-3 transgene in pregnancy-responsive breast tumors.

We have developed transgenic mice in which expression of the mouse int-2/Fgf-3 gene is regulated by a single long terminal repeat from mouse mammary tumor virus. Such mice contain and transmit a replica of the activated int-2/Fgf-3 allele present in a spontaneous mammary tumor from a BR6 mouse. Although free of infectious mouse mammary tumor virus and with a different genetic background, the transgenic mice develop pregnancy-responsive mammary epithelial proliferations that are similar to the early stages of tumorigenesis in the BR6 strain. Histological examination revealed that most of these tumors showed pronounced tubular and acinar structures, features usually associated with morphological differentiation. In some cases, the tumors were locally invasive, causing disruption of the dermis which manifested itself as local hair loss. In situ hybridization showed that patterns of transgene expression in the abnormal glands were markedly nonuniform. In contrast, mouse mammary tumor virus-induced neoplasms showed more uniform expression of int-2/Fgf-3, as did the urogenital epithelial proliferations that occur among males of this transgenic line. These data suggest that mammary tumors in virally infected animals may depend primarily on autocrine stimulation by the int-2/Fgf-3 gene product, whereas both autocrine and paracrine mechanisms may contribute to tumors and hyperplasias found in transgenic animals.

Animals↗
PubMed1992

Proviral insertions near cyclin D1 in mouse lymphomas: a parallel for BCL1 translocations in human B-cell neoplasms.

By isolating genomic DNA clones that encompass the mouse Cyl-1 (cyclin D1) locus, we have identified a putative CpG island close to the 5' end of the gene. Pulsed-field gel electrophoresis with probes derived from either the 5' or 3' side of the CpG island established physical linkage to two independent markers on mouse chromosome 7, in a region that is syntenic with human chromosome 11q13. On the 3' side, Cyl-1 is approximately 75 kb from Hst-1 and Int-2, although there is an additional CpG island in the intervening DNA, while on the 5' side, Cyl-1 is less than 300 kb from Fis-1, an integration site for Friend murine leukaemia virus. As there is no intervening CpG island, proviral insertions at Fis-1 could influence the expression of Cyl-1 and we describe two virally induced tumours in which this appears to be the case. The data suggest that proviral insertions near Cyl-1 in mouse lymphomas are functionally equivalent to the BCL1 translocations that activate cyclin D1 expression in human B-cell malignancies.

Animals↗
PubMed1991

[Infections caused by staphylococci. The human as a source of infection for S. aureus and coagulase negative staphylococci].

Both Staphylococcus aureus and coagulase-negative staphylococci are among the most important pathogens of nosocomial infections. While Staphylococcus aureus can cause a variety of pyogenic infections and toxin-mediated diseases coagulase-negative staphylococci of the Staphylococcus epidermis group play an important role in infections developing in immunocompromised patients and those with temporarily or permanently implanted foreign bodies made of polymer. The major sources of staphylococcal infections are the skin and mucosa in humans. While in the case of Staphylococcus aureus the infection route may be either endogenous or exogenous, in the case of coagulase-negative staphylococci, the endogenous route predominates. This ecological-epidemiological situation forms the basis for strategies aimed at preventing nosocomial staphylococcal infections.

Coagulase↗
PubMed1991

[A protracted course in Cardiobacterium hominis endocarditis].

A 69-year-old man without previous cardiac disease was found over the last 9 months to have a markedly elevated erythrocyte sedimentation rate (ESR: 120 mm/1. h), haemolytic anaemia (haemoglobin 8.2 g/dl, lactate dehydrogenase 304 U/l), markedly reduced exercise tolerance, backache and weight loss of 5 kg. Radiological, biochemical and endoscopic examinations failed to provide a diagnosis. Nine blood cultures grew, at normal body temperature, Cardiobacterium hominis, a rare Gram-negative organism which can cause endocarditis. Echocardiography revealed endocarditis of the aortic valve with regurgitation. Despite protracted and high-dosage antibiotics (4 times daily 10 million U penicillin G for 6 days, followed by four times 5 million U penicillin G for 6 days, followed by four times 5 million U daily for five weeks, and three times daily 60 mg gentamycin for 10 days), as well as treatment of extensive chronic parodontitis, anaemia, haemolysis and increased ESR have now persisted for over a year, with negative blood cultures. Immune-complex phenomena are thought to be the reason for the persistence of signs of infection.

Aged↗