Biomedical subjects

H Werner

Publications and source records attributed to H Werner.

448 records · Page 25Linked to original sources

PubMedDate not supplied

Regulation of the insulin-like growth factor-I receptor gene by oncogenes and antioncogenes: implications in human cancer.

The insulin-like growth factor-I receptor (IGF-I-R) has a central role in normal cellular proliferation as well as in transformation processes. Transcription of the IGF-I receptor gene is controlled by a number of tumor suppressors, including WT1, p53, and BRCA1. It has been demonstrated that, in their wild-type form, these transcription factors can suppress the activity of the IGF-I-R promoter, with ensuing reduction in the levels of cell-surface IGF binding. On the other hand, a number of oncogenes, including mutant p53 and c-myb, and the fusion protein EWS-WT1 significantly stimulate promoter activity. Interactions between stimulatory and inhibitory transcription factors may determine the level of expression of the IGF-I-R gene and, consequently, the proliferative status of the cell.

Apoptosis↗

PubMedDate not supplied

Efficacy of sulbactam in an in vitro model of mixed aerobic/anaerobic infections.

Bacterial interactions in mixed infections may interfere with antimicrobial therapy. The in-vitro efficacy of ampicillin alone, combination sulbactam/ampicillin, and metronidazole was studied. Strains of Bacteroides fragilis, Escherichia coli, and Enterococcus faecalis, alone and in association, were tested by means of a broth dilution method. Minimal bactericidal concentrations (MBC) of ampicillin for B. fragilis 74 in association with E. coli 68 were up to 16-fold higher than for B. fragilis 74 alone (256 compared to 16 mg/l), but only 2-fold higher for sulbactam (5 mg/l)/ampicillin (0.5 and 0.25 g/l). Association of B. fragilis 45 and E. faecalis 186 increased ampicillin MBC of E. faecalis 186 from 2 to 16 mg/l, but the combination sulbactam/ampicillin restored activity of ampicillin. In association with E. faecalis, metronidazole MBCs of B. fragilis increased up to 64-fold. Strains of E. faecalis and E. coli were able to destroy 10 mg/l metronidazole within 8 to 20 h. The present experiments demonstrated effectiveness of sulbactam/ampicillin to inhibit beta-lactamases of associated pathogens. Destruction of metronidazole by E. faecalis lends additional support to the use of the combination in aerobic/anaerobic infections including E. faecalis.

Ampicillin↗

PubMedDate not supplied

Association experiments with aerobic and anaerobic pathogens: a model of in-vitro susceptibility testing in mixed infections. Activity of enoxacin, clindamycin, and metronidazole.

In infections of polymicrobial etiology, it seems mandatory to combine an antibiotic with marginal activity against anaerobes with an anti-anaerobic drug, e.g. metronidazole or clindamycin. We investigated the effect of associations of anaerobic and facultatively anaerobic pathogens on MBCs of enoxacin, clindamycin, metronidazole, and combinations of enoxacin plus clindamycin or metronidazole. Single testing, and associations of Bacteroides fragilis with Escherichia coli or Enterococcus faecalis revealed MBCs of 64 mg/l for enoxacin. However, investigating metronidazole, MBCs for B. fragilis increased from 0.5-1 mg/l to 2-4 mg/l in association with E. coli. The combination of enoxacin with metronidazole restored MBCs of 0.5 and 1 mg/l for the B. fragilis strains. B. fragilis associated with E. faecalis showed MBCs of 2 to 64 mg/l for metronidazole, an increase of up to 64-fold. The enoxacin MBCs for E. coli in association with B. fragilis were up to eight-fold higher than for E. coli alone (2 mg/l compared to 0.25 mg/l). Association of E. coli with E. faecalis and B. fragilis showed a low to moderate increase for MBCs of E. coli when enoxacin was tested alone or in combination with metronidazole or clindamycin. In contrast, MBCs for E. faecalis did not change significantly with any of the associations or combinations tested. It is evident that in vitro antimicrobial susceptibility of associations of pathogens can be modified by interactions between strains, and/or antimicrobials.

Bacteria, Aerobic↗

PubMedDate not supplied

Comparative in vitro activity of cefpodoxime against anaerobes other than Bacteroides fragilis.

To assess the in vitro activity of cefpodoxime against anaerobic respiratory tract and oropharyngeal pathogens 77 strains belonging to 18 gram-negative and 7 gram-positive species were studied by means of agar dilution tests. For comparison cefuroxime, amoxicillin, amoxicillin + clavulanic acid and clindamycin were also tested. Cefpodoxime was found to be active at concentrations of less than or equal to 0.125 mg/l against Prevotella oralis, Prevotella buccalis, Prevotella bivia, Porphyromonas asaccharolytica, Bacteroides corporis, Bacteroides gracilis, Fusobacterium necrophorum, Fusobacterium naviforme and Propionibacterium acnes. Prevotella oris, Prevotella buccae, Fusobacterium nucleatum, Peptostreptococcus asaccharolyticus, and Ruminococcus bromii were inhibited at concentrations of less than or equal to 1 mg/l and Prevotella denticola, Prevotella melaninogenica, Prevotella intermedia, Porphyromonas gingivalis, Bacteroides pneumosintes, and Peptostreptococcus micros at concentrations of less than or equal to 4 mg/l. Strains of Veillonella parvula were inhibited by cefpodoxime at 0.25-8 mg/l, and single strains of Peptostreptococcus anaerobius and Peptostreptococcus magnus showed MICs of 32 and 64 mg/l, respectively. The results obtained warrant the use of cefpodoxime in therapy of anaerobic and mixed aerobic-anaerobic infections of the upper and lower respiratory tract and similar infections not involving Bacteroides fragilis.

Anti-Bacterial Agents↗

PubMedDate not supplied

Immunoreactive and bioactive somatostatin-like material is present in tobacco (Nicotiana tabacum).

Immunoreactive and biologically active somatostatin-like material is present in extracts of tobacco plants (Nicotiana tabacum). Comparative chromatographic and immunological characterization of this peptide along with synthetic (hypothalamic-like) somatostatin-14 and -28, indicates that both molecular forms are present in the plant. Tobacco-somatostatin inhibits the prostaglandin E2-induced release of growth hormone from cultured anterior pituitary cells. This finding raises questions concerning the evolutionary mechanisms responsible for the presence of this neuropeptide in plants, and the physiological significance of this phenomena.

Animals↗

PubMedDate not supplied

Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene.

The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of the IGFs, and is critical for normal mammary gland development as well as for malignant transformation. Transcription of the IGF-IR gene is under inhibitory control by a number of transcription factors with tumor suppressor activity, including BRCA1 and p53. To assess the potential functional interactions between BRCA1 and p53 in transcriptional control of the IGF-IR gene, co-transfections were performed on MCF-7 breast cancer cells using an IGF-IR promoter luciferase reporter construct together with expression vectors encoding BRCA1 and wild-type and mutant p53. Similar experiments were performed in the colorectal cancer cell line HCT116 (+/+), which expresses a wild-type p53 gene, and its HCT116 (-/-) derivative, which lacks p53. BRCA1 was able to suppress IGF-IR promoter activity both in the absence and presence of p53. However, BRCA1 had no effect in mutant p53-expressing cells. Co-immunoprecipitation experiments showed that BRCA1 and p53 physically interact. In summary, our data suggest that the transcriptional activity of BRCA1 depends on the cellular status of p53. Inability of mutant tumor suppressors to repress IGF-IR gene expression may result in increased IGF-IR levels and IGF binding, leading to a reduction in apoptosis and enhanced survival capacity of malignant cells.

BRCA1 Protein↗

PubMedDate not supplied

Insulin-like growth factors.

The insulin-like growth factors (IGF-I and IGF-II) play important roles in the regulation of growth and metabolism. While the liver is the main source of circulating IGFs, their production by numerous extrahepatic tissues suggests the existence of autocrine and paracrine modes of action in addition to typical endocrine mechanisms. The actions of the IGFs are mediated through their activation of specific cell surface receptors, primarily the IGF-I receptor, although some effects may be mediated through the IGF-II receptor and the insulin receptor. The stability of the IGFs and their interaction with their receptors are mediated by specific IGF binding proteins (IGF-BPs) which are found in the circulation and in extracellular fluids. Thus, the overall biological actions of the IGFs can be regulated by control of ligand biosynthesis, modulation of receptor levels and postreceptor signalling pathways, and changes in the levels and activity of IGF-BPs.

Animals↗

PubMedDate not supplied

Zn2Mg alkaline phosphatase in an early ptolemeic mummy.

Bone samples of a ptolemeic mummy have been employed to study the mode of conservation on the intactness of Zn2Mg alkaline phosphatase in both structure and catalytic activity. A protein of M(r) = 190 +/- 10 kDa being identical to the 200 kDa enzyme of fresh human bones was successfully isolated. Regardless of age 200 kDa protein bands and a distinct subunit at 60 kDa were seen in SDS-PAGE electrophoresis. The 200 kDa band was also monitored by activity staining. The specific activity was 120 mU/mg and 65% of the respective activity obtained in the identical preparation using fresh human tibia or rib. The enzymic activity was inhibited in the presence of 1,10-phenanthroline and L-homoarginine. Radiocarbon dating supported the assignment of the mummy to the early ptolemeic period. Among the many bactericidal and fungicidal components employed for mummification were aromatic alcohols, mono- and sesquiterpenes. Pistachio resin was the major balm resin used. The microbiological sterility of the bone surface was ascertained by independent bacterial and fungal examinations.

Alcohols↗

PubMedDate not supplied

Determination of cell mediated immunity against tumour associated antigens in patients of ENT.

In an unconventional assay system (MEM Test) Caspary & Field claimed in 1971 to have detected lymphocyte sensitization to a common tumour antigen in all patients with cancer. There was no evidence of histogenetic specificity to the reaction and their conclusions are in direct contradiction to those of all workers who have studied the cytotoxic activity of lymphocytes on tumour cells. To improve the specificity of the test system, another type of tumour antigen was used in MEM Test incubation. Tumour-associated antigens were prepared according to the hypertonic salt extraction method introduced by Reisfeld, Leonard, Meltzer et al. As shown by the results, information could be gained concerning the existence of a malignant tumour and its location.

Antigens, Neoplasm↗

PubMedDate not supplied