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Biomedical subjects

H Werner

Publications and source records attributed to H Werner.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cationic and neutral diphenyldiazomethanerhodium(I) complexes as catalytically active species in the C-C coupling reaction of olefins and diphenyldiazomethane

Cationic rhodium(I) complexes cis-[Rh(acetone)2(L)(L')]+ (2: L = L'=C8H14; 3: L=C8H14; L'=PiPr3; 4: L=L'=PiPr3), prepared from [RhCl(C8H14)2]2] and isolated as PF6 salts, catalyze the C-C coupling reaction of diphenyldiazomethane with ethene, propene, and styrene. In most cases, a mixture of isomeric olefins and cyclopropanes were obtained which are formally built up by one equivalent of RCH=CH2 (R = H, Me, Ph) and one equivalent of CPh2. The efficiency and selectivity of the catalyst depends significantly on the coordination sphere around the rhodium(I) center. Treatment of 4 with Ph2CN2 in the molar ratio of 1:1 and 1:2 gave the complexes trans-[Rh(PiPr3)2(acetone)(eta1-N2CPh2)]PF6 (8) and trans-[Rh(PiPr3)2(eta1-N2CPh2)2]PF6 (9), of which 8 was characterized by X-ray crystallography. Since 8 and 9 not only react with ethene but also catalyze the reaction of C2H4 and free Ph2CN2, they can be regarded as intermediates (possibly resting states) in the C-C coupling process. The lability of 8 and 9 is illustrated by the reactions with pyridine and NaX (X=Cl, Br, I, N3) which afford the mono(diphenyldiazomethane)rhodium(I) compounds trans-[Rh(PiPr3)2(py)(eta1-N2CPh2)]PF6 (10) and trans-[RhX(eta1-N2CPh2)(PiPr3)2] (11-14), respectively. The catalytic activity of the neutral complexes 11 - 14 is somewhat less than that of the cationic species 8, 9 and decreases in the order Cl > Br> I > N3.

Journal Article↗
PubMed2000

An Unprecedented

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

BRCA1 suppresses insulin-like growth factor-I receptor promoter activity: potential interaction between BRCA1 and Sp1.

The insulin-like growth factor I receptor (IGF-I-R) has an important role in breast cancer etiology. The receptor is overexpressed by most breast cancers, where it functions as a potent antiapoptotic agent. BRCA1 is a tumor suppressor gene that is mutated in a large fraction of familial breast and ovarian cancers. Cotransfection of Saos-2, MCF7, and CHO cells with IGF-I-R promoter constructs driving luciferase reporter genes, and with a BRCA1 expression vector, suppressed promoter activity in a dose-dependent manner. Functional interactions between BRCA1 and Sp1 in the regulation of the IGF-I-R gene were studied in Schneider cells, a Drosophila cell line which lacks endogenous Sp1. In these cells BRCA1 suppressed 45% of the Sp1-induced trans-activation of the IGF-I-R promoter. These results suggest that BRCA1 is capable of suppressing the IGF-I-R promoter in a number of cell lines, thus resulting in low levels of receptor mRNA and protein. Mutant versions of BRCA1 lacking trans-activational activity can potentially derepress the IGF-I-R promoter. Activation of the overexpressed receptor by locally produced or circulating IGFs may be a crucial step in breast and ovarian cancer progression.

Animals↗
PubMed2000

New concepts in regulation and function of the insulin-like growth factors: implications for understanding normal growth and neoplasia.

The insulin-like growth factors (IGFs) are a ubiquitous family of growth factors, binding proteins and receptors that are involved in normal growth and development. They are also implicated in numerous pathological states, including malignancy. IGF-II is a commonly expressed growth factor in many tumors and may enhance tumor growth, acting via the overexpressed IGF-I receptor, a cell-surface tyrosine kinase receptor. The IGF-I receptor may be overexpressed due to mutations in tumor suppression gene products such as p53 and WT-1 or growth factors such as bFGF and PDGF. Thus, this family of growth factors, especially the IGF-I receptor, may present an excellent target for new therapeutic agents in the treatment of cancer and other disorders of excessive cellular proliferation.

Animals↗
PubMed2000

[Infection in the elderly--what is different?].

Infectious diseases are a common cause of increased morbidity and mortality in elderly patients and present a frequent problem in the geriatrician's daily practice. Infections in the elderly are quite different from infections in a younger population. These differences are due to Age-related alterations in immunology Different epidemiology and bacteriology Increased morbidity and mortality Altered clinical presentation Concommittant disability and comorbidity in many older patients Different approaches to therapy. This article is an attempt to discuss these various aspects of infectious disease in the elderly. The most important infections in the elderly are caused by bacteria. Incidence and bacterial spectrum depends on the site of infection and whether the patient is hospitalized, living in a nursing home or in the community. Pneumonia, UTI and pressure ulcer infections are more frequent in patients living in nursing homes than in community dwelling older people. Infections are a frequent cause of hospitalization in elderly people and hospitalization on the other hand is a risk factor for life-threatening nosocomial infections, caused by invasive diagnostic procedures and frequent use of urinary and venous catheters. Infections in the elderly are often accompanied by serious complications as bacteriemia (pneumonia), frequent recurrence (UTI), perforation and abscess (abdominal infections) and severe disability (pressure ulcer infections). Because of these serious and frequent complications mortality of infections is higher in older patients than in younger people. Elderly patients with infectious disease often present in the same way as younger patients do. Many elderly however present with non-specific clinical symptoms and non-specific functional decline which makes an accurate diagnosis difficult and may lead to a life-threatening delay of diagnosis and therapy. In older patients with unexplained functional decline, physicians must be aware of the possibility of a serious infection. Moreover, the physician can not rely on typical signs of infections as fever. In the elderly the fever response is often blunted even in the presence of bacteremia. Leokocytosis may be absent and elevation of acute phase protein is a more reliable marker of infection than elevation of erythrocyte sedimentation rate. Clinical suspicion of bacterial infection in elderly patient should prompt Careful anamnesis and clinical investigation Hospitalization if necessary Diagnostic procedures without delay including blood cultures Immediate empiric antibiotic therapy taking into account the site of infection, if the infection is community acquired or nosocomial and the most likely bacterial spectrum and local resistance factors. The use of broad spectrum antibiotic substances with a low side effect profile and pharmacokinetic properties which are suitable for elderly patients.

Aged↗
PubMed2000

Structure activity relationships for bradykinin antagonists on the inhibition of cytokine release and the release of histamine.

Highly potent bradykinin antagonists were found to inhibit bradykinin-induced release of cytokines but to stimulate histamine release. Both actions show structural requirements completely different from those for bradykinin B1 and B2 receptors, indicating that the release of some cytokines from spleen mononuclear cells and of histamine from rat mast cells is not mediated by these receptors. Most potent bradykinin antagonists release histamine at lower concentrations than does bradykinin itself. Dimers of bradykinin antagonists are the most potent compounds for histamine release. In contrast to enhanced histamine release, potent inhibition of cytokine release enhances the applicability of these compounds as anti-inflammatory drugs. Many of the peptides designed for high B2-receptor antagonism were found to be compared by their concentrations far more potent for inhibition of cytokine release than for smooth muscle contraction. Thus, for some antagonists inhibition of cytokine release was detected at concentrations as low as 10(-15) M. The rational design of peptide and nonpeptide bradykinin antagonists for therapeutic use requires not only knowledge about the potency but also knowledge about the structure-activity relationships of such important side effects as cytokine and histamine release.

Amino Acid Substitution↗
PubMed2000

Seasonal ozone response of mature beech trees (Fagus sylvatica) at high altitude in the Bavarian forest (Germany) in comparison with young beech grown in the field and in phytotrons.

Mature beech trees (Fagus sylvatica) grown at two different altitudes in the Bavarian forest were compared with young beech trees grown at nearby field sites or in phytotrons for their macroscopic and physiological responses to different ozone (O(3)) exposures. Cumulative O(3) exposure expressed as the sum of hourly mean concentrations above the canopy ranged between 100 and 150 microl l(-1) h, with the vertical O(3) profiles at the higher altitude site being enhanced by 30%. O(3) profiles at all sites were reduced by up to 20% with increasing depth within and beneath the canopy. The leaf discoloration that developed in the absence of premature leaf loss was similar in the sun foliage of mature and young trees (including plant grown in the phytotron). Injury became apparent at low O(3) exposures, expressed as accumulated hourly means over a threshold of 40 nl l(-1) (AOT40 <3.5 microl l(-1) h) at the lower site in both the mature trees and the young beech at the field site, but only occurred when AOT40 values reached 7 microl l(-1) h at the upper site, and 6 microl l(-1) h in the phytotrons. However, the association between injury and O(3) exposure was improved when cumulative ozone uptake to sun leaves was the ozone index, used with values of about 3 mmol m(-2) resulting in visible injury in both mature and young beech growing in phytotrons. Under high ozone exposure levels of inositol were lowered, whilst concentrations of lignin-like materials were enhanced in mature beech. Similar responses were observed in young beech grown in phytotrons. As the sun foliage was affected by only a small and variable extent each year, the seasonal O(3) impact at high altitude did not appear to pose an acute risk to mature beech trees.

Journal Article↗
PubMed1999

Acute ventilatory restriction in children after weaning off inhaled nitric oxide: relation to rebound pulmonary hypertension.

OBJECTIVE: To assess the interaction between pulmonary hemodynamics and respiratory mechanics during acute pulmonary hypertension. PATIENTS: Ventilated and paralysed children treated with inhaled nitric oxide because of post-operative pulmonary hypertension. INTERVENTIONS: Weaning of inhaled nitric oxide. MEASUREMENTS: Air flow and airway pressure, calculation of dynamic respiratory system compliance and respiratory system resistance for each breath by multiple linear regression. RESULTS: In four patients, increases in pulmonary arterial pressure from 26.1 to 56.7 mm Hg (p<0.001) during weaning off nitric oxide were associated with decreases in tidal volume (from 9.7-->8.2 ml/kg, p<0.01) and reductions in dynamic respiratory system compliance (from 0.52-->0.34 cm H20/ml/kg, p<0.001), while respiratory system resistance was unchanged. CONCLUSIONS: Impaired ventilation during acute pulmonary hypertension is predominantly related to a reduction in respiratory system compliance.

Administration, Inhalation↗
PubMed1999

Field intercomparison of diffusive samplers for measuring ammonia.

Agricultural production systems are recognised as a major source of atmospheric ammonia. Deposition of ammonia and ammonium may contribute to undesired changes in oligotrophic ecosystems. The continuous measurement of atmospheric ammonia requires expensive and sophisticated techniques and is performed only in a very restrict number of ambient air stations in Europe. Therefore, the application of passive samplers, which have the advantage of being easy to handle and cost-efficient, is useful. In the past the comparability of different passive samplers must be considered as rather scarce. In a joint European project under the leadership of the GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, in 1997 a comparison of different passive ammonia monitoring methods was carried out in a prealpine rural site near Garmisch-Partenkirchen. It was considered valuable to include not only well established systems but also methods still being developed. For the comparative test ten working groups with different methods took part. A wet annular denuder system, which has been developed by the Netherlands Energy Research Foundation for on-line measurement of atmospheric ammonia, served as reference of passive methods. The experiment, which started in June and finished in December, showed that most of the passive samplers fulfil the requirements and can be recommended for further measurements. Additional measurements of meteorological parameters were performed to check the influences of different weather conditions on passive sampling.

Agriculture↗
PubMed1999

In vitro and in vivo responses to short-term recombinant human insulin-like growth factor-1 (IGF-I) in a severely growth-retarded girl with ring chromosome 15 and deletion of a single allele for the type 1 IGF receptor gene.

OBJECTIVES: Patients with single allele defects in the gene encoding the type 1 IGF receptor have been reported to have growth failure, but fibroblasts from affected patients have not exhibited insensitivity to the effects of IGF-I in vitro. The in vitro and in vivo responses to short-term recombinant human IGF-I (rhIGF-I) in a severely growth-retarded girl with ring chromosome 15 and deletion of a single allele for the type 1 IGF receptor gene have been investigated. DESIGN AND PATIENT: The child exhibited prenatal and severe post-natal growth failure, and delayed psychomotor development. Southern blotting revealed a 50% reduction in IGF-I receptor DNA, and in an RNase protection assay (RPA), a quantitatively similar reduction in steady-state mRNA for type 1 IGF receptor. rhIGF-I was administered in graded doses of 40, 60 and 80 microg/kg twice daily by subcutaneous injection for periods of 2-2.5 days each. RESULTS: During rhIGF-I treatment, mean urinary nitrogen excretion was unchanged and urinary calcium rose to 60% greater than in the pre-treatment period. rhIGF-I injections produced only a modest decrease in indices of GH secretion, assessed by frequent (every 20 min) sampling over periods of 12 h. There was no significant difference between the mean GH concentrations during rhIGF-I treatment (5.32 +/- 6.2 mU/l) compared with that before rhIGF-I treatment (8.46 +/- 10.2 mU/l). Mean IGFBP-3-values were increased (4.5 mg/l before vs. 5.4 mg/l during rhIGF-I). TSH values after injection of TRH were not significantly reduced by IGF-I (mean of all values, 18.6 mU/l vs. 15.5 mU/l during rhIGF-I treatment). In vitro binding of radiolabelled IGF-I to the patient's fibroblasts was less than that bound by control fibroblasts (patient, 0.69% binding by 248 000 cells, vs. 1.41% binding by 260 000 fibroblasts from an age-matched control). However, the patient's fibroblasts exhibited a growth response in vitro to the addition of IGF-I in a fashion similar to that of control fibroblasts. CONCLUSIONS: These studies show evidence in each of the indices examined of in vivo resistance to IGF-I and suggest that the growth retardation observed in such patients may be the direct result of the absence of one of the alleles encoding the type 1 IGF receptor.

Blotting, Southern↗
PubMed1999

Tumor necrosis factor alpha and interferon gamma--induced cell growth arrest is mediated via insulin-like growth factor binding protein-3.

Retinoic acid (RA), and the combination of TNFalpha and Interferon (IFN-gamma) inhibit human salivary gland tumor (HSG) cell growth with the combination of all three being even more inhibitory (P<0. 05). Previous studies have demonstrated that these inhibitory effects of RA, and the combination of TNFalpha and IFN-gamma are associated with increased accumulation of IGFBP-3 in the culture medium of HSG cells. Therefore, we set out to determine if the increase in IGFBP-3 was due to increased production of IGFBP-3 by the cells and whether IGFBP-3 played a causative role in the inhibition of cellular proliferation. TNFalpha and IFN-gamma induced a rise in IGFBP-3 mRNA levels between 4 and 8 h, which returned to control levels after 24 h. IGFBP-3 was shown to inhibit HSG cell growth at concentrations of >/=75 U (P<0.05). When antibodies to IGFBP-3 were used with TNFalpha and IFN-gamma, the inhibitory effect of the cytokines on cell growth was diminished. Retinoic acid with TNFalpha and IFN-gamma had a marked inhibitory effect (P<0.05) which was similarly reversed by increasing concentrations of IGFBP-3 antibody. The present data support the hypothesis that the combination of TNFalpha and IFN-gamma with retinoic acid exert their anti-proliferative effect on HSG cells by reducing the mitogenic effect of IGF-I due to a shift in IGF-I from the free to the IGFBP-3-bound form.

Blotting, Northern↗