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Biomedical subjects

P Metz

Publications and source records attributed to P Metz.

At least 19 recordsLinked to original sources

Platelet-endothelial cell interactions in murine antigen-induced arthritis.

OBJECTIVES: Growing evidence supports the substantial pathophysiological impact of platelets on the development of rheumatoid arthritis. At present there are no methods for studying these cellular mechanisms in vivo. The aim of this study was to visualize and investigate platelet-endothelial cell interaction in the knee joint of mice with antigen-induced arthritis (AiA) by means of intravital microscopy. METHODS: In 14 mice (Balbc) intravital microscopic assessment was performed on day 8 after AiA induction in two groups (controls, AiA). The severity of AiA was assessed by measuring knee joint swelling and by histological scoring. Ex vivo fluorescently labelled rolling and adherent platelets and leucocyte-endothelium interactions were investigated by intravital fluorescence microscopy. RESULTS: Swelling of the knee joint as well as histological score was significantly enhanced in arthritic animals compared with controls. In control mice intravital microscopy revealed low baseline rolling and sticking of leucocytes and fluorescently labelled platelets. AiA induced a significant increase in the fraction of rolling leucocytes (3 times) and rolling platelets (6 times) compared to the control group. Furthermore, AiA induction resulted in a significantly enhanced number of adherent leucocytes (3-fold) and adherent platelets (12-fold) in comparison with control animals. CONCLUSIONS: Platelet kinetics were directly analysed using intravital microscopy in the arthritic microcirculation in vivo for the first time. We provide the first evidence that platelets accumulate in arthritic vessels, indicating platelet activation due to AiA. Platelet recruitment and subsequent activation might play an important role in the pathogenesis of rheumatoid arthritis.

Animals↗

Antimycobacterial activity of synthetic pamamycins.

OBJECTIVES: Early studies have indicated that pamamycins, a group of macrodiolides first isolated from Streptomyces alboniger, have potent antimicrobial activity against Gram-positive bacteria, fungi and mycobacteria but not against Gram-negative bacteria. The recent availability of highly purified and reasonable quantities of several pamamycins through their total syntheses has rendered possible more extensive studies on their effects on mycobacteria. METHODS: Bioluminescent strains of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis, expressing the luxA and luxB genes from Vibrio harveyi were used for the comparison of the antimycobacterial activity of the two synthetic macrodiolides pamamycin-607 and pamamycin-621A and a non-naturally occurring cyclic dimer of pamamycin-607, i.e. yukomycin. RESULTS: Pamamycin-607 was the most active of the three macrocycles and was more active against M. tuberculosis than against M. smegmatis. Twenty-five clinical isolates of M. tuberculosis were susceptible to pamamycin-607 in a narrow MIC range of 1.5-2.0 mg/L. The new assay was also validated by comparison with the BACTEC radiometric test. CONCLUSION: Rapid screening of a new class of macrocyclic antimycobacterials using bioluminescent mycobacteria identified pamamycin-607 as a potential antituberculous agent. The latter was active against clinical isolates of M. tuberculosis within a narrow MIC range of 1.5-2.0 mg/L irrespective of their resistance to isoniazid or rifampicin. Our findings warrant further investigations.

Anti-Bacterial Agents↗

Measurement of Lagrangian velocity in fully developed turbulence.

We have developed a new experimental technique to measure the Lagrangian velocity of tracer particles in a turbulent flow, based on ultrasonic Doppler tracking. This method yields a direct access to the velocity of a single particle at a turbulent Reynolds number R(lambda) = 740, with two decades of time resolution, below the Lagrangian correlation time. We observe that the Lagrangian velocity spectrum has a Lorentzian form E(L)(omega) = u(2)(rms)T(L)/[1+(T(L)omega)(2)], in agreement with a Kolmogorov-like scaling in the inertial range. The probability density functions of the velocity time increments display an intermittency which is more pronounced than that of the corresponding Eulerian spatial increments.

Journal Article↗

Intracavernous self-injection with vasoactive intestinal polypeptide and phentolamine in the management of erectile failure.

A total of 52 men, median age 55 years (range 28 to 74 years), with erectile failure was treated with vasoactive intestinal polypeptide and phentolamine. Impotence was classified as psychogenic in 3 patients, psychogenic/arteriogenic in 3, arteriogenic in 25, arteriogenic/neurogenic in 4, neurogenic in 5, venous leakage/psychogenic in 2, venous leakage/neurogenic in 1 and following venous leak surgery in 9. The patients were treated with 30 micrograms vasoactive intestinal polypeptide and 0.5 to 2.0 mg. phentolamine. A total of 1,380 self-injections was given and the number of injections per patient varied from 5 to 245. No patient had priapism, corporeal fibrosis or other serious complications. After sexual stimulation all patients obtained erection sufficient for penetration. Following ejaculation rigidity decreased normally. The median duration of treatment was 6 months (range 1 to 22). Nine patients discontinued treatment. One patient with severe arteriosclerosis experienced decreased effectiveness of the drug and received a penile prosthesis. Five patients elected not to perform self-injection any longer, 1 psychogenic impotent patient was cured, and 1 patient discontinued therapy due to palpitation and sweating. One patient died of a myocardial infarction not associated with this therapy.

Adult↗

Low dose loop diuretics in essential hypertension. Experience with torasemide.

Diuretics belong to the class of antihypertensive drugs recommended for first-line therapy of essential hypertension. Although they are widely and effectively used for the treatment of hypertension, the question remains whether their possible negative influence on metabolic and electrolyte parameters could partly offset the benefit of blood pressure reduction with respect to reduction of coronary artery disease. Recently published data demonstrate that much lower doses of thiazides exert the same antihypertensive effect as the higher doses used in the past and even prescribed today. These lower doses produce relatively little change in biochemical parameters. Thus, the postulated risks can be avoided by using the lowest effective dose. Traditionally, loop diuretics of the furosemide (frusemide) type are rarely used as first-line antihypertensive agents. They seem to display less efficacy coupled with an intense diuresis when used in standard available doses. However, there is evidence that newly developed loop diuretics, in lower doses than used in congestive heart failure, are effective antihypertensive agents. For example, torasemide 2.5mg once daily, which does not exert a significant diuresis over 24 hours compared with placebo, lowers elevated blood pressure to a similar extent than thiazides or related compounds. This antihypertensive effect is accompanied by less, if any, changes in metabolic or electrolyte parameters compared with widely used standard diuretics such as hydrochlorothiazide, indapamide or chlorthalidone. The influence on serum potassium and magnesium is similar to or even less than fixed combinations of hydrochlorothiazide and triamterene or amiloride. Thus, low-dose torasemide constitutes an alternative to established thiazide antihypertensive therapy.

Diuretics↗

Purification and characterization of glucose-6-phosphate dehydrogenase from Pseudomonas W6.

Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) has been purified from methanol grown Pseudomonas W6 by a simple procedure involving dye-ligand affinity chromatography on Cibacronblue F3G-A-Sephadex and Procion Red HE-3B-Sepharose. The purification procedure yielded a homogeneous enzyme with (1) high specific activity of 390 and 500 units/mg with NADP and NAD, respectively, and (2) low concentrations of contaminating activities. The molecular mass of the native enzyme was estimated to be 123 +/- 5 kDa. For the polypeptide chain after SDS denaturation a molecular mass of about 61 kDa was calculated. The kinetic behaviour of glucose-6-phosphate dehydrogenase exhibiting activity with either NADP or NAD was studied with respect to the substrate and coenzyme affinities and to ATP inhibition of enzyme activity. The applicability of prepared glucose-6-phosphate dehydrogenase as an auxiliary enzyme in clinical tests is discussed.

Chromatography, Affinity↗

Interaction of bacterial glucose-6-phosphate dehydrogenase with triazine dyes: a study by means of affinity partitioning and kinetic analysis.

The interaction of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) from Pseudomonas W6 with 33 triazine dyes bound to poly(ethylene glycol) has been screened by means of affinity partition in an aqueous two-phase system composed of poly-(ethylene glycol) and dextran. Regarding the strength of interaction expressed by the affinity partitioning effect three groups of dyes can be distinguished showing high, medium or low interaction to the enzyme. The different influence of the structurally related dyes Cibacronblue F3G-A, Procion Blue MX-3G and Procion Blue MX-R on the partitioning of glucose-6-phosphate dehydrogenase is discussed. Both coenzymes of this glucose-6-phosphate dehydrogenase, NADP+ and NAD+, are able to diminish the dye-enzyme interactions but to a different extent. In the case of Procion Red HE-3B less than 0.2 mM of NADP+ abolished completely the dye-protein interaction indicating that the dye binding site might be closely related to the nucleotide binding site. This does not hold for a series of other dyes revealing strong interactions to the enzyme. In these cases higher NADP(+)-concentrations are necessary to weaken the dye-enzyme interactions. Only small influences on the interaction between the dye and glucose-6-phosphate dehydrogenase were found with 1 mM NAD+. The different effects of the two coenzymes are discussed with respect to separate binding sites for them and to different conformational states induced. The competition of Procion Red HE-3B with NADP+ and NAD+ for the binding site of glucose-6-phosphate dehydrogenase was also demonstrated by inhibition studies. The Ki-values of Procion Red HE-3B with NAD+ and NADP+, respectively, were calculated.

Bacterial Proteins↗

Affinity chromatography of bovine heart lactate dehydrogenase using dye ligands linked directly or spacer-mediated to bead cellulose.

A number of reactive dyes coupled to bead cellulose directly or spacer-mediated has been investigated in respect of their interaction with lactate dehydrogenase (LDH; E.C. 1.1.1.28) from heart muscle. The Procion dyes Red HE-7B and Navy H-ER, as well as the Remazol dyes Brilliant Blue R and Brilliant Red 5-BN directly bound to bead cellulose provide high binding of LDH and the adsorbed enzyme is eluted specifically from these affinity adsorbents in high yield. In contrast, under the same conditions no binding of LDH has been found to the Procion dyes Green H-4G, Yellow HE-3G, Scarlet MX-G and Orange MX-G, although an opposite behaviour was expected from the results of affinity partitioning in aqueous two-phase systems. However, immobilizing these dyes via a spacer generated strong binding of the enzyme to the affinity adsorbent. The influence of the length of the spacer was studied in respect of the binding capacity and the yield of the enzyme specifically eluted. The applicability of Procion Scarlet MX-G-(diaminohexyl)-bead cellulose for the purification of LDH from muscle extract in one chromatographic step was demonstrated.

Animals↗

Inhibitory effect of tetracycline and doxycycline on resistance of mice to infection with a tetracycline-resistant strain of Listeria monocytogenes.

By transposon mutagenesis a tetracycline-susceptible strain of Listeria monocytogenes (MIC 1 mg/l. for tetracycline and 0.25 mg/l. for doxycycline) was rendered resistant (MIC 64 mg/l. for tetracycline and 16 mg/l. for doxycycline). Infection of mice with this resistant strain led to an acute infection. Treatment with 2 x 2 mg tetracycline per day did not influence the course of infection during the first 3 days, indicating that the nonspecific resistance, mediated mainly by macrophages and granulocytes, was not affected by this treatment. The second phase of infection, characterized by a continuous resistance to infection due to macrophages activated by T-lymphocytes was, however, definitely hampered. Even acquired immunity to a secondary infection was impaired by treatment with tetracycline, indicating that cell-mediated immunity can be blocked. The course of infection of athymic, nude mice which are unable to build up a cell-mediated immune response, was not affected by tetracycline treatment. Doxycycline expressed the same activities as tetracycline.

Animals↗

[Comments on the contribution: initial results of surgical treatment of scoliosis with the Cotrel and Dubousset CD instruments by Ch. Hopf, H. H. Matthiass and J. Heine. Z. Orthop. 125 (1987) 347].

It really must be appreciated that in the above mentioned publication of Hopf, Heine and Matthiass the authors were brave enough-against normal habits-to publish their bad results. In demonstrating their cases they render the CD system a destructive rebuff. Not in one of their demonstrated cases they were able to show that there are convincing advantages of this surgery compared to other already wellknown and sufficiently proven methods. We still have to acknowledge the opinion of Nachemson (1986) that the CD method is yet in the experimental stage. The authors show in their selective cases how it should not be done. They sacrifice in favor of a primary stability functionally important segments of the spine cranially as well as caudally and thus mutilate young human beings to an irresponsible extent. Of course it is astonishing when the authors in spite of their actually crushing experiments with this system in summary arrive at positive results without reasons indeed. For example they comment positively on the attained derotation, although they had shown with their results that no derotation could be achieved at all. Remarks about diminishing the rib hump, which should after all be a result of a good derotation are missing. Exact measurements in CT scans of the apical vertebra, as demonstrated in an extraordinary way by Giehl, have not yet been made in Münster. Otherwise the authors would have clearly recognized that a derotation with resection of the discs is not possible using the CD method. The authors present the system-in spite of their very bad results-as a universal spinal system for correction and stabilization and at the same time they doubt the value and extent of anterior surgical methods according to Dwyer or Zielke, even though these methods have internationally shown how the optimal corrections have resulted in fewer mutilations by using shorter fusion areas on the spine provided that the surgeon knows how to use the instruments. We spine surgeons should always be aware that we can cause an irreversible condition on the spine of the human being with our spinal fusion operation this could have grave results for the patient for his whole life. No doubt, there are advantages in the CD method, but they rather result in better stability than in better corrections.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Comparative study on the antihypertensive efficacy of torasemide and indapamide in patients with essential hypertension.

In a double-blind randomized multicenter study the antihypertensive efficacy of 2.5 mg torasemide (1- isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfony)urea) and 2.5 mg indapamide was compared in patients with essential hypertension, known as responders to diuretic therapy. After a wash-out period of 4 weeks patients with a sitting diastolic blood pressure of 100-115 mmHg were included in the 12-weeks active treatment period. After 4 weeks of treatment with a once daily 2.5 mg dose of each drug, doses could once be doubled if blood-pressure decrease was considered to be insufficient. 66 patients qualified for the statistical evaluation, 32 in the torasemide group and 34 in the indapamide group. In these patients both drugs caused a similar fall in blood pressure leading to a normalization of blood pressure in most of the patients. Serum parameters remained within normal limits. Only serum potassium was significantly lower with 2.5 mg indapamide compared to 2.5 mg torasemide at the end of the study. No side effects were reported for both drugs. As the lowest effective dose of a diuretic should be used for the treatment of hypertensive patients, 2.5 mg torasemide, which is below the threshold dose for significantly enhanced diuresis, seems to be the recommended dose for antihypertensive treatment.

Adult↗

Congenital penile angulation.

Congenital penile angulation without epispadias and hypospadias (Krummerik) is more frequent than previously believed, and the prevalence seems to be higher than 0.4/1000. The malformation, which may threaten the sex life of young patients, can be corrected by a simple out-patient operation.

Adolescent↗