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Biomedical subjects

G Peters

Publications and source records attributed to G Peters.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

[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

[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

Two-dimensional transesophageal echocardiographic determination of aortic valve area in adults with aortic stenosis.

To determine if aortic stenosis severity could be accurately measured by two-dimensional transesophageal echocardiography (TEE), 62 adult subjects (mean age 66 +/- 12 years) with aortic stenosis had their aortic valve area (AVA) determined by direct planimetry using TEE, and with the continuity equation using combined transthoracic Doppler and two-dimensional echocardiography (TTE). Eighteen subjects had AVA calculated by the Gorlin method during catheterization. An excellent correlation (r = 0.93, SEE = 0.17 cm2) was found between AVA determined by TEE (mean 1.24 +/- 0.49 cm2; range 0.40 to 2.26 cm2) and TTE (mean 1.23 +/- 0.46 cm2; range 0.40 to 2.23 cm2). The absolute (0.13 +/- 0.12 cm2) and percent (10.8 +/- 8.9%) differences between AVA determined by TEE versus TTE were small. Excellent correlations between AVA by TEE and TTE were also found in subjects with normal systolic function (r = 0.95, SEE = 0.14 cm2; n = 38) and impaired function (r = 0.91, SEE = 0.21 cm2; n = 24). AVA determined by catheterization correlated better with AVA measured by TEE (r = 0.91, SEE = 0.15 cm2) than AVA measured with TTE (r = 0.84, SEE = 0.19 cm2). These data demonstrate that AVA can be accurately measured by direct planimetry using TEE in subjects with aortic stenosis. TEE may become an important adjunct to transthoracic echocardiography in the assessment of aortic stenosis severity.

Adult

Modern strategies in the prevention of polymer-associated infections.

Foreign body infections continue to present a challenge to modern medicine. New aspects for the prevention of such infections are presented on the basis of modifying medical devices or implant materials (synthetic polymers). Physicochemical treatment of polymer surfaces is a possible tool to create anti-adhesive and thus anti-infective surfaces. Coupling or incorporation of antimicrobial substances to or into polymers is another way to prevent bacterial colonization and subsequently the development of polymer-associated infections.

Anti-Bacterial Agents

Evidence for degradation of synthetic polyurethanes by Staphylococcus epidermidis.

The survival of Staphylococcus epidermidis strain KH 11 in the presence of synthetic high molecular polyurethanes was prolonged in comparison to control experiments performed in the absence of any nutrients. Investigations of the bacteria after contact with the polymers revealed changes in their surface properties and metabolism, in particular a marked induction of urease activity. ESCA (Electron Spectroscopy for Chemical Analysis) measurements detected a decrease in elementary nitrogen in the polyurethane surfaces after incubation with the bacteria. The alterations observed indicate an urease-induced degradation of synthetic polymers by Staphylococcus epidermidis KH 11.

Absorption

Cell transformation by kFGF requires secretion but not glycosylation.

The Kfgf gene, which encodes a member of the fibroblast growth factor family, was originally discovered by assaying human tumor DNA for dominantly transforming oncogenes. The 22-kD kFGF product contains a single site for asparagine-linked glycosylation and an amino-terminal signal peptide for vectorial synthesis into the endoplasmic reticulum and eventual secretion. To determine whether these features are necessary for transformation, we have constructed mutants of kFGF that are impaired for glycosylation or secretion. All mutants retained the ability to induce DNA synthesis when added to quiescent cells, and the absence of glycosylation had no appreciable effect on the transformation efficiency on NIH3T3 cells. In contrast, mutants of kFGF that remain in the cytoplasm or are retained in the secretory pathway, through addition of a KDEL motif, score negative in standard transformation assays. Since transformation by either the glycosylated or unglycosylated form of kFGF can be reversed by addition of suramin, the data imply that secretion of kFGF, or surface localization of the ligand/receptor complex, is a prerequisite for transformation.

Animals

The Int-2/Fgf-3 oncogene product is secreted and associates with extracellular matrix: implications for cell transformation.

NIH3T3 cells transformed by mouse Int-2/Fgf-3 cDNA express a series of Int-2-related products representing discrete stages of processing and glycosylation. We confirm that in at least two highly transformed clonal lines, Int-2 products acquire further modifications and are efficiently secreted into the culture medium. Secreted proteins become associated with the cell surface and extracellular matrix and can be displaced by addition of soluble glycosaminoglycans, specifically heparin, heparan sulfate, and dermatan sulfate. Increasing concentrations of heparin not only compete for Int-2 binding in a dose-dependent manner but also inhibit the growth of these cells and revert the transformed phenotype. These findings reaffirm the notion that extracellular or surface-bound Int-2 protein is instrumental in the morphological transformation of these cells.

3T3 Cells