In vitro activity of cefpodoxime against staphylococci in comparison to other cephalosporins.
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Biomedical subjects
Publications and source records attributed to G Peters.
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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.
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.
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.
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.
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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.
A case of severe endophthalmitis after cataract extraction followed by posterior chamber lens implantation is reported. Microbiological cultures from a tap of the patient's aqueous humour prior to lens explantation as well as from the explanted lens and aqueous and vitreous humour during operation yielded Staphylococcus epidermidis sensu stricto. Scanning electron microscopy showed massive colonisation of the lens loop by staphylococci. Clonal identity of all isolates was demonstrated by plasmid DNA analysis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of extra-cellular products. This is strongly suggestive of the aetiological role of S. epidermidis in this case of late onset endophthalmitis.
Polymer-associated infection is a problem of increasing importance in modern medicine. In a new approach to prevent such infections we have modified polyvinylfluoride (TEDLAR) films by graft copolymerization with N-vinylpyrrolidone to which iodine can be complexed. Grafting reaction was performed by the preirradiation technique using an electron accelerator. Grafted films were then treated in Lugol's solution for at least 24 h. Release of free iodine from the films was determined either by titration or using the agar disc diffusion test, showing an iodine release for up to 4-5 days. The antimicrobial activity of the films was tested in bacterial adhesion measurements. Bacterial and fungal cells in the range of 10(3) to 10(6) cfu/cm2 polymer were found on control samples without iodine, whereas on iodine-complexed films no viable cells could be detected at least for 5 days or even longer. Thus, microbial adhesion and growth can be inhibited by iodine-containing polymers.
The int-2 gene, which encodes a member of the fibroblast growth factor family, is expressed at specific sites and times during mouse development. In certain embryonal carcinoma cell lines, multiple int-2 transcripts accumulate when the cells are induced to differentiate with retinoic acid and dibutyryl cyclic AMP. Nuclear run-on analyses indicate that the apparent induction of int-2 expression results from an increase in the rate of transcription initiation. Six distinct types of RNA have been delineated, originating from three promoters and terminating at either of two polyadenylation sites. Since each transcript appears to encode the same protein, this complexity may reflect the need for lineage-specific or differentiation-dependent control of expression. By comparing the kinetics of induction and turnover of the different RNA species, we show that the choice of promoter or length of the 3'-untranslated region has no significant effect on the half-lives of the various mRNAs. To further evaluate control at the transcriptional level, we have shown that a 1.7-kilobase fragment of int-2 genomic DNA, when fused to the chloramphenicol acetyltransferase gene, can act as a regulated promoter(s) in differentiated versus undifferentiated embryonal carcinoma cells. This segment of DNA encompasses the three promoter regions previously delineated by RNase mapping plus about 900 base pairs of additional upstream sequences.
Structural abnormalities affecting band q13 of chromosome 11 have been reported in a variety of human tumors, particularly multiple endocrine neoplasia type 1 (MEN1), certain low-grade B-cell neoplasms, and a significant subset of breast and squamous cell carcinomas. The perturbations of the region are also varied, ranging from allele loss and deletions to specific translocations and DNA amplification. Given their clinical relevance in classifying tumors and identifying patients at increased risk, it is important to locate and characterize the genes on which these aberrations impinge. Here we assess the candidate genes identified thus far and the evidence that implicates them in tumorigenesis.
Nosocomial infections are among the most serious complications encountered in surgical intensive care. The most sufficient antibacterial chemotherapy of these infections is generally based on basic and empiric principles. This includes a correct decision as to the necessity for chemotherapy and the appropriate establishment of dosage, treatment duration, drug monitoring and efficacy control. Several antibiotic regimes for the treatment of the most common nosocomial infections, i.e. pneumonia, peritonitis and sepsis, are discussed.
The sequence similarities between Int-2 and members of the fibroblast growth factor (FGF) family have prompted functional as well as structural comparisons with other FGFs. Here we examine the ability of int-2 sequences to induced morphological transformation of NIH3T3 cells, a characteristic property of the secreted FGFs, such as FGF-5 and Hst1/kFGF. Despite encoding a short signal sequence, which directs the product to the secretory pathway, mouse int-2 DNA is incapable of inducing foci of transformation in the standard transfection assay. However, when transfected cells are enriched by co-selection with the neomycin resistance gene, a proportion of the int-2-expressing cells display a transformed phenotype, including the ability to grow as colonies in soft agar and in defined medium. Analyses of int-2 RNA and protein in these cells suggest that transformation by int-2 may require a threshold level of expression, and that the subsequent phenotype is dependent on the level of int-2 protein present in the cells.
Infections associated with indwelling devices have become a major problem in modern medicine. Coagulase-negative staphylococci and to a lesser extent Staphylococcus aureus, enterobacteriaceae und fungi are the predominant causative organisms in the etiology of these infections. The general features of the pathogenesis of foreign body infections are discussed, as are the clinical picture and therapy. Special emphasis is given to the occurrence of polymer-associated infections in urological devices such as penile prostheses and to their prevention and therapy.
Approximately 15 to 20% of primary breast cancers and an even higher proportion of squamous cell carcinomas of the head and neck show amplification of DNA markers on band q13 of human chromosome 11. However, known genes within the amplified region, such as the FGF-related oncogenes INT-2 and HST-1, are very rarely expressed in these tumors. Here we show that another candidate oncogene, designated D11S287, implicated in the pathogenesis of parathyroid adenomas, is also amplified in breast cancers. Significantly, it is consistently coamplified with INT-2 and HST-1 in 36 out of 202 primary tumors, including one case in which the amplified unit did not encompass the translocation breakpoint marker BCL-1. This implies that D11S287 is on the same side of the breakpoint as INT-2, and pulsed-field gel electrophoresis indicates that D11S287 is less than 250 kb from the BCL-1 marker. Since D11S287 RNA was present at elevated levels in a group of tumors and cell lines in which the 11q13 region is amplified, it may be the key oncogene on this amplified unit, and could also be activated by BCL-1 translocations.
Fibroblast growth factors (FGFs) have been implicated in many aspects of cell growth and differentiation both in normal and neoplastic settings. For example, the mouse int-2 gene, which encodes an FGF-related product, is a frequent target of proviral activation in carcinomas induced by mouse mammary tumour virus, but apparently functions at discrete stages of normal embryonic development. Six classes of int-2 messenger RNA have been identified in embryonic cells, each of which is predicted to encode the same 245-amino-acid protein. But all known int-2 transcripts include sequences upstream of the AUG codon presumed to be the initiation codon. Here we report an additional N-terminally extended int-2 gene product initiated at an in-frame CUG codon. In COS-1 cells transiently transfected with appropriate int-2 complementary DNAs, the AUG-initiated product is found predominantly in the secretory pathway, whereas the CUG-initiated form is localized to the nucleus. These data indicate that the Int-2 oncoprotein could influence cellular behaviour by two distinct mechanisms.
The induction of mammary tumors by mouse mammary tumor virus (MMTV) is thought to occur through proviral activation of one or more cellular genes. One of these, int-2, encodes a 27 kd protein which exhibits striking homology to the basic fibroblast growth factor family. To assess directly the role of the int-2 protein in cell proliferation, we have established transgenic mice which carry the int-2 gene driven by the MMTV promoter/enhancer. Expression of the int-2 gene in female transgenic mice results in pronounced mammary gland hyperplasia. Interestingly, expression of the MMTV-int-2 transgene in the prostate gland of male carriers results in a benign, but dramatic, epithelial hyperplasia similar to benign prostatic hypertrophy (BPH), a common but poorly understood disorder in human populations. Together, these results indicate that the int-2 product can act as a potent growth factor in these epithelial tissues.
The serotonin antagonist pizotifen (BC-105) is prescribed as an appetite and weight enhancer (Mosegor--Wander, also commercialized under brand names Sanmigran or Sandomigran--Sandoz, Switzerland) for anorectic and convalescent humans. There has been, however, difficulty in demonstrating any orexigenic effect of pizotifen in laboratory animals. In the present report, the influence of chronic administration of pizotifen (0.1-30.0 mg/kg b.wt. per day, SC) on food intake and body weight gains was studied in rats given a standard diet (SD-energy content 14.5 kJ/g, 9% fibre), and in rats either habituated to a low energy content, carbohydrate-free diet (DD-7.3 kJ/g, 45% fibre), or given the DD after habituation to the SD. Pizotifen failed to increase food intake or weight gain. Nor did it shorten a period of initial depression of intake of the unfamiliar DD. On the contrary, pizotifen seemed to diminish food intake and weight gain in rats fed the low energy content diet. Since it has been reported that other 5-HT antagonists, e.g., cyproheptadine, methysergide, and ritanserin can enhance feeding, it is of some interest that pizotifen failed to affect food intake or weight gain in rats. The results suggest that the effects of pizotifen (and, possibly, of serotonin) in rats may differ from those in man. The possibility that feeding in the rat is mediated by 5-HT1 rather than 5-HT2 receptors is discussed.