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Biomedical subjects

H Haag

Publications and source records attributed to H Haag.

At least 19 recordsLinked to original sources

Staphylococcus aureus positive for Panton-Valentine leukocidin genes but susceptible to methicillin in patients with furuncles.

A total of 75 Staphylococcus aureus isolates obtained from patients with either recurrent skin abscesses or furuncles (n=48) or chronic infections from other body sites (n=27) were screened for the presence of the lukS-PV and lukF-PV genes encoding Panton-Valentine leukocidin. Significantly more isolates (70.8% vs. 7.4%, p<0.001) from patients suffering skin abscesses or furuncles were positive for lukS-PV and lukF-PV. These isolates belonged to the accessory gene regulator (agr) group Ia (9/48), group III (13/48), or group IV (19/48). In contrast with results of other investigations, none of the isolates positive for the Panton-Valentine leukocidin genes in this study exhibited methicillin resistance.

Abscess↗

Liquid chromatography-electrospray time-of-flight mass spectrometry for on-line accurate mass determination and identification of cyclodepsipeptides in a crude extract of the fungus Metarrhizium anisopliae.

Electrospray ionisation time-of-flight mass spectrometry (ESI-TOF-MS) has been used for the detection and identification of destruxins (cyclodepsipeptides) in a crude extract of the fungus Metarrhizium anisopliae. HPLC-MS analyses were performed with a post-column addition of erythromycin as a reference compound (lock mass procedure). Seven destruxin derivatives could be identified on-line from their accurate masses (deviation from calculated values <5.5 ppm) through elemental composition calculations. As a highly sensitive and accurate method, ESI-TOF-MS proved to be very powerful for the analysis and dereplication of natural products in complex mixtures.

Chromatography, High Pressure Liquid↗

Isolation and biological characterization of staphyloferrin B, a compound with siderophore activity from staphylococci.

A highly hydrophilic compound with siderophore activity has been isolated from the supernatant of Staphylococcus hyicus DSM 20459 grown under iron-restricted conditions. The metabolite, named staphyloferrin B, is strictly iron-regulated and produced by a large variety of staphylococci strains. In vivo iron transport measurements and the growth-promoting activity in a bioassay establish staphyloferrin B as the second siderophore for staphylococci besides the previously described staphyloferrin A. The structure elucidation revealed 2,3-diaminopropionic acid, citrate, ethylenediamine and 2-ketoglutaric acid as structural components of the compound. Thus, staphyloferrin B is a structurally new siderophore of the complexone type.

Biological Assay↗

Lovastatin inhibits receptor-stimulated Ca(2+)-influx in retinoic acid differentiated U937 and HL-60 cells.

Lovastatin was used to study the role of isoprenylated proteins on stimulus-induced increase of cytosolic Ca2+ in retinoic acid-differentiated U937 and HL-60 cells. Preincubation of the cells with lovastatin for 11-24 h reduced the Ca(2+)-influx induced by PAF of FMLP. The maximal decrease was 60% in U937 cells and 40% in HL-60 cells. The ID50s of lovastatin in U937 and HL-60 cells were 5 microM and 15 microM, respectively. Lovastatin did not inhibit Ca(2+)-discharge from intracellular stores. Addition of mevalonate to lovastatin-treated cells completely reversed the inhibition of PAF- and FMLP-stimulated Ca(2+)-mobilization. Immunoreactivity of ras-like proteins was decreased in membranes and increased in the cytosol of U937 cells by 1 day treatment with lovastatin. We conclude that isoprenylated proteins are involved in the regulation of receptor-stimulated Ca(2+)-entry of differentiated HL-60 and U937 cells.

Calcium↗

Tumor necrosis factor induces enhanced responses to platelet-activating factor and differentiation in human monocytic Mono Mac 6 cells.

Human Mono Mac 6 cells exhibit characteristics of mature blood monocytes. Treatment of these cells with human recombinant human tumor necrosis factor (TNF) resulted in an increase in phagocytosis and phorbol myristate acetate-stimulated superoxide anion production at 12 h and growth retardation occurring at 24 h. Moreover, TNF induced a moderate increase of CD14 surface antigen expression, used as a phenotypic marker of monocyte/macrophage differentiation. Platelet-activating factor (PAF) stimulated a rapid rise in cytosolic free Ca++ ([Ca++]i) of 308 +/- 93 nM in TNF-treated cells compared to untreated cells (33 +/- 8 nM, n = 4). The effect of TNF was dose and time dependent, evident after 12 h and maximal at 48 h. The enhanced PAF-induced [Ca++]i rise was inhibited by the PAF receptor antagonist L-659,989 and EGTA, indicating receptor-dependent Ca++ influx. Furthermore, L-659,989 and PAF inhibited specific 3H-labeled PAF binding in TNF-treated, but not in untreated cells. Consistently, PAF stimulated arachidonic acid release only in TNF-treated cells. Preincubation of cells with anti-TNF monoclonal antibodies abolished TNF-induced effects, but failed to block lipopolysaccharide (LPS) effects. Distinct mechanisms of action by LPS were reflected by the different ability to induce surface antigen expression. In conclusion, the enhancement of PAF responses by TNF, associated with functional characteristics of differentiation in Mono Mac 6 cells, may represent a specific mechanism of cooperative interaction between PAF and TNF in inflammation, sepsis, immunoregulation and atherogenesis.

Antigens, CD↗

Purification and chemical characterization of staphyloferrin B, a hydrophilic siderophore from staphylococci.

This paper describes the chemical characterization of staphyloferrin B, a new complexone type siderophore isolated from low iron cultures of Staphylococcus hyicus DSM 20459. Purification of the very hydrophilic metabolite was achieved by anion exchange high performance liquid chromatography HPLC. Mass spectrometry showed a molecular mass of 448 amu. Hydrolysis with 8 M HCl revealed the presence of L-2,3-diaminopropionic acid, citrate, ethylenediamine and succinic semialdehyde. The connections between the four building blocks were determined by two-dimensional nuclear magnetic resonance measurements. UV/Vis and circular dichroism spectra are consistent with the proposed structure, which could also be confirmed by precursor feeding. The siderophore activity of staphyloferrin B was demonstrated by iron transport measurements.

Citrates↗

Novel bioactive compounds from Actinomycetes: a short review (1988-1992).

Novel secondary metabolites continue to be isolated from Actinomycetes. Their biological activities and chemical structures show a wide range of diversity. This short review provides information on the compounds isolated between 1988 and 1992, and highlights interesting substances discovered during screening.

Actinomycetales↗

Purification of yersiniabactin: a siderophore and possible virulence factor of Yersinia enterocolitica.

HPLC analysis revealed that Yersinia enterocolitica WA-C produced two substances under iron-limiting conditions one of which was identified as 2,3-dihydroxybenzoyl-L-serine. The other compound had iron-complexing activity and was called yersiniabactin. The fur mutant H1852 was shown to produce yersiniabactin constitutively in an iron-independent manner. Yersiniabactin was isolated by ethyl acetate extraction from the spent medium of H1852, size-fractionation chromatography and preparative HPLC. A catechol function was demonstrated with different chemical assays and by UV-visible spectroscopy. The molecular mass of yersiniabactin was determined to be 482 Da. Purified yersiniabactin stimulated growth of Y. enterocolitica and Escherichia coli phi under iron-limiting conditions and apparently served as an iron carrier. Transport of 55Fe-yersiniabactin was TonB-dependent, indicating a receptor-mediated uptake across the outer membrane. A pesticin-resistant mutant missing the receptor protein FyuA was unable to transport and use yersiniabactin as a siderophore.

Bacterial Outer Membrane Proteins↗

Isolation and characterization of staphyloferrin A, a compound with siderophore activity from Staphylococcus hyicus DSM 20459.

A highly hydrophilic compound was isolated from low iron culture broth of Staphylococcus hyicus DSM 20459 which exhibits siderophore activity to the producer and 37 other staphylococci. The previously unknown metabolite was designated staphyloferrin A and consists of two molecules of citric acid, each linked to D-ornitine by an amide bond. Using an ion-pair HPLC-system we detected staphyloferrin A and a second iron regulated compound (staphyloferrin B) in the culture fluid of several Staphylococcus strains. We found no evidence that staphylococci synthesize catecholor hydroxamate-type siderophores.

Chromatography, High Pressure Liquid↗

Lithium response and the sequence of episode polarities: preliminary report on a Hamilton sample.

This is a preliminary report on a study which replicated the finding of a significant relationship between the response to long-term lithium stabilization and the sequence of episode polarities (depressive/manic) in bipolar and schizoaffective (bipolar) patients. The lithium response and the clinical course data were assessed independently, in a blind manner, utilizing a data collection which has been gathered in earlier studies. There was a significant association between lithium response (stability achieved on long-term lithium treatment) and the sequence of episode polarities. The main determinant of this association was a close link between lithium response and the MDI sequence of episode polarities. The observed association may be explained in several ways: as an artifact; due to the exclusively antimanic effect of lithium; due to true psychobiological differences between mania and depression; as a result of the differences between bipolar type one and type two patients; and finally due to bipolar heterogeneity. Considering the data available to date the explanation via bipolar heterogeneity appears to be the most likely one.

Bipolar Disorder↗

Sequence of affective polarity and lithium response: preliminary report on Munich sample.

As an alternative to the bipolar I/II distinction, a subtyping of bipolar affective disorders according to the sequence of polarity (mania or depression) has been proposed. In a study of 93 patients with bipolar affective and bipolar schizoaffective disorders we tested the stability of a subtyping using the sequence of polarity. Furthermore we investigated its relationship to bipolar I/II subtypes and to response to stabilizing therapy with lithium. In the individual patient the first sequence of polarity significantly predicted the same sequence of polarity of further manifestations. However, only half of the patients could be classified as either MDI (mania-depression-interval) or DMI (depression-mania-interval). Subtyping according to the sequence of polarity was not significantly related to the bipolar I/II subgroups. MDI patients showed a significantly better response to stabilizing therapy with lithium than DMI patients. Our findings lend support to the notion that the polarity sequence is of clinical relevance. The observed association between polarity sequence and effectiveness of lithium prophylaxis could be linked to direct consequences of a MDI or DMI sequence (e.g.: different treatment approaches). On the other hand, a difference in polarity sequence might be the clinical expression of a difference in the underlying mechanisms of dysregulation, which in turn might be more or less prone to respond to lithium therapy.

Bipolar Disorder↗

RBC-choline: a biological marker of the outcome of lithium prophylaxis?

We explored whether the elevation of RBC-choline and choline ratio (RBC-choline/plasma-choline) by lithium is a specific effect of lithium, whether these choline parameters are characteristics of the individual patient, and whether they are related to prophylactic lithium response. In lithium-treated patients RBC-choline and choline ratio were highly elevated compared with untreated controls. In contrast, both values were slightly decreased in patients on antidepressants, and essentially unchanged in patients on neuroleptics. Repeated measurements showed that choline parameters were fairly stable in the individual patient. The interindividual variance was significantly greater than the intraindividual variance. In 58 affective disorder patients with established lithium response, high choline ratios were found to be associated with a poor outcome of stabilizing therapy with lithium. This finding was replicated in a new sample of 15 bipolar patients. If confirmed, it could be an important clue as to the mode of action of lithium.

Alcoholism↗

[Preoperative (neoadjuvant) chemotherapy of small cell bronchial cancer].

The high rate of locally delimited recurrences of parvicellular bronchial carcinoma, following chemotherapy and complete remission, primarily in cases of limited disease, prompted the authors to apply preoperative neoadjuvant chemotherapy to seven patients. Four of them were without tumours for six to 72 months from treatment. One patient died of myocardial infarction but with no tumour detectable 15 months after treatment. Locally delimited recurrence with additional lymphogenic spreading was recorded from one patient only. Two patients died of haematogenic metastasation. The concept should be tested for efficiency on larger groups of patients.

Aged↗

Tiapride: effects on tardive dyskinesia and on prolactin plasma concentrations.

In a placebo-controlled double-blind crossover study of 21 patients chronically treated with neuroleptics and suffering from tardive dyskinesia, tiapride (600 mg/day, mean plasma level: 682 ng/ml) exhibited a transient efficacy during 12 weeks of treatment, most distinct in the 6th week (p less than 0.01). Tiapride induced an increase of prolactin plasma levels, on the average, from 1,195 to 2,179 microIU/ml (p less than 0.01). Tiapride was well tolerated. Increase of parkinsonism was only mild and not significant. The results underline the difficulty in treating tardive dyskinesia and, thus, confirm the importance of prevention.

Aged↗

RBC-choline: changes by lithium and relation to prophylactic response.

Red blood cell (RBC)- and plasma-choline levels were measured in patients on lithium (n = 96), antidepressants (n = 32) and neuroleptics (n = 51), and in 25 healthy drug-free controls. Lithium patients exhibited highly increased RBC- and slightly increased plasma-choline levels compared with controls (P less than 0.001 and P less than 0.05, respectively); the choline ratio (RBC-/plasma-choline) was elevated almost to the same extent as RBC-choline (P less than 0.001). With antidepressants RBC-choline and choline ratios were slightly reduced (P less than 0.05), whereas neuroleptics showed no effect on choline levels. 79% of lithium patients were responders (reduction in hospitalizations with lithium), 21% were non-responders (no reduction or increase in hospitalizations). Choline ratio exhibited a significant relation to prophylactic lithium response, but lithium ratio did not. The percentage of non-responders was significantly higher in patients with a choline ratio exceeding 100 than in patients with a choline ratio below this cut-off (P less than 0.01). Thus, the increase of RBC-choline and choline ratios appears to be an effect specific for lithium and might be related to the outcome of lithium prophylaxis.

Age Factors↗

Effect of anticholinergics on tardive dyskinesia. A controlled discontinuation study.

In a double-blind, placebo-controlled study, ten chronic schizophrenic patients with pronounced symptoms of tardive dyskinesia (TD) were withdrawn from anticholinergic medication. All patients had previously been under long-term treatment with neuroleptics and anticholinergics for at least two years. The rating-scales used were the AIMS, our own TD Scale, and the Simpson-Angus scale for extra-pyramidal side-effects. The severity of TD decreased significantly in nine patients with in two weeks; this improvement, most pronounced in the oral region (P less than .001), persisted during a six-week placebo period. There was a slight increase in parkinsonian symptoms (P less than .05), which was not a prerequisite for improvement in TD. Hence, discontinuation of anticholinergic medication is a possible therapeutic approach in patients with TD.

Adult↗