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Biomedical subjects

W Meyer

Publications and source records attributed to W Meyer.

At least 55 records · Page 3Linked to original sources

The effect of high-dose pentaerythritol tetranitrate on the development of nitrate tolerance in rabbits.

Experimental studies with therapeutic doses of pentaerythritol tetranitrate (PETN) have shown unexpected actions such as a lack of nitrate tolerance and vasoprotective effects in atherosclerosis. We investigated the effect of a 3-week treatment with low- (6 mg kg(-1) day(-1), n=10) and high-dose (100 mg kg(-1) day(-1), n=10) oral PETN given twice daily on the development of nitrate tolerance in rabbits. We measured aortic relaxation in response to acetylcholine, S-nitroso-N-acetyl-D,L-penicillamine and PETN, constriction in response to phenylephrine and production of reactive oxygen species (ROS). Mean aortic pressure (AOPmean) and heart rate were measured after a single oral dose of PETN (50 mg kg(-1), n=6) and after increasing doses of pentaerythritol dinitrate (PEDN, n=5) and pentaerythritol mononitrate (PEMN, n=5) in anaesthetized rabbits. Oral PETN, even at high dosage, was not associated with nitrate tolerance. None of the aortic ring studies showed a difference in the responses to the vasodilators, while the vasoconstriction to phenylephrine was slightly reduced in both PETN groups. The production of vascular ROS was also not different. Oral PETN reduced AOPmean transiently (-19.3+/-4.4%, P<0.01 vs. controls) and i.v. administration of both PEMN and PEDN reduced AOPmean dose dependently (P<0.05, ANOVA). These results suggest that oral PETN elicits minor nitrate tolerance. This unique feature might be due to the slow onset of vasodilator activity of the predominantly active metabolites PEDN and PEMN and might contribute to the vasoprotective activity of PETN in atherosclerosis.

Animals↗

Prognostic importance of isolated peritumoral lymphangiosis carcinomatosa in lymph-node-negative colorectal carcinoma.

BACKGROUND: The prognostic value of microinvasion of lymph vessels and lymph nodes has become increasingly important; there is a wide range in prognosis of patients with nodal-negative tumor stages after curative resection for colorectal cancer. AIM: Detection of the prognostic importance of isolated lymph-vessel invasion as a possible precursor of lymph-node metastasis in patients with nodal-negative tumor stages. PATIENTS/METHODS: Retrospective analysis of 894 patients with R0-resected colorectal cancer, uni- and multivariate analysis of tumorbiologic prognostic factors, immunohistochemical proof of tumor cells in negative lymph nodes (pN0) using the epithelial marker HEA-125 (human epithelial antigen). RESULTS: The incidence of lymph-vessel invasion (L) was 37.7% in total. A pN0,L1 status was found in 144 patients (16.1% of all analyzed patients). Comparing patients with pN0,L1 status to those with pN+,L0 status showed that both groups have similar rates of overall survival and tumor relapse. Lymph-node status, lymph-vessel invasion, depth of tumor infiltration (pT) stage, and age were detected as independent prognostic factors by multivariate analysis. After reanalysis of 54 cases primarily classified as 18.5% pN0,L1, microinvasion in lymph nodes was detected by immunohistochemistry. We found a higher rate of tumor relapse (approximately 20%) for those patients. In regard to the overall survival rate, however, there was no difference when compared to patients without immunohistochemical proof of microinvasion. CONCLUSION: Isolated lymph-vessel invasion in nodal-negative tumor stages and a lymph-node-positive tumor status have equivalent prognostic importance in colorectal cancer.

Aged↗

Resuscitation decision index: a new approach to decision-making in prehospital CPR.

Retrospective and prospective studies have been undertaken to assess physicians' practice-patterns by studying cardiopulmonary resuscitation (CPR) case summaries. Most summaries reveal similar influences by the physician, patient and situation-related variables on the patterns of resuscitation. The initiation of resuscitation efforts is addressed frequently, but, very few studies discuss the topic of termination of resuscitation. Prehospital emergencies are addressed very rarely. The objective of this study was to introduce a new methodological approach towards initiation and termination of resuscitation efforts in prehospital situations. The subject studied were the physicians' decisions concerning initiation/withholding, termination/withdrawal and the resulting early survival rates. The result is termed the "Resuscitation decision index" (RDI). The "RDI" could be a tool allowing comparisons on a quantitative level, between different EMS systems or disciplines and giving an insight into the decision process. The "RDI" can enhance audit of resuscitation. The process of decision-making can be used to help future theoretical decision-making strategies.

Adult↗

General anti-microbial properties of the integument in fleece producing sheep and goats.

Based on lectin histochemical methods, this study describes the production and distribution of various terminal sugars in the integument of Merino sheep and Angora goats. Additionally, pH measurements were performed for information about environmental conditions of microbes on the skin surface and in the fleece. The results demonstrated strongly positive reactions for alpha-L-fucose in the stratum corneum of Merino sheep, and in the secretions of the skin glands of Angora goats. Moreover, alpha-D-mannose, beta-D-N-acetylglucosamine, alpha-D-N-acetylgalactosamine, alpha-D-galactose and beta-D-galactose were very distinct in the secretions of the skin glands of both species. The skin products containing saccharide residues are deposited on the skin surface and in the fleece as part of wool grease, and the terminal sugars may be liberated by bacterial and fungal activities. All of these sugars are of specific interest because of their ability of inhibiting the adherence of different bacteria and fungi to the epidermal cells. Thus, free sugars impede attacks of skin micro-inhabitants against the integrity of the epidermal barrier. In contrast to these results, the skin pH-conditions were strongly alkaline, particularly in the fleece of Merino sheep (pH 6-9), so that proliferation of microbes may be promoted. This negative influence can only be countered by high production rates of sugar-containing skin products, which is normally the case based on long and intense activity of hair follicles in fine-wool producing sheep and goats.In conclusion, this study demonstrates that a basic anti-microbial biological system exists on the skin surface and within the hair coat, that operates with free sugars before the immune system is activated.

Journal Article↗

Lectin histochemistry of glycoconjugates in the feline hair follicle and hair.

The distribution of glycoconjugate in the feline hair follicle and hair was studied by light and electron microscopic histochemical methods. The hair apparatus was found to contain considerable amounts of complex carbohydrates with different saccharide residues (alpha-D-mannose, beta-D-glucose, alpha-L-fucose, beta-N-acetyl-D-glucosamine). Variations of those were detected in the plasma membrane of the hair follicle cells during the course of their differentiation and keratinization, namely, alph-D-glucose, alpha-L-fucose and beta-N-acetyl-D-glucosamine in the suprabulbar and bulbar regions. The reaction level of sialic acid residues in the plasma membrane decreased in some cell layers during the course of differentiation. The results obtained from the present study indicated that interaction between saccharide residues of neutral carbohydrates and sialyl groups during the anagen phase might contribute to cell keratinization in hair follicles and hairs. It is discussed whether the existence of glycogen in outer root sheath cells might enable these cells to provide other hair apparatus cells with energy when necessary. Moreover, it became obvious from variations in sialyl residue distribution that cell differentiation processes terminate first of all in Huxley's and Henle's layers within the suprabulbar region of the hair follicle, as followed by the hair cortex.

Animals↗

Ultracytochemistry of glycosaminoglycans in the canine knee synovium.

The accurate localization and nature of glycosaminoglycans (GAGs) in the canine knee synovium were studied by ultracytochemical methods that involved high or low iron diamine-thiocarbohydrazide-silver proteinate (physical development) staining in combination with enzyme digestion control procedures. The results obtained indicated that heparan sulfates and hyaluronan were present mainly in the plasma membrane of the B (fibroblast-like) cells. In contrast, the plasma membrane of the A (macrophage-like) cells showed negative reactions after the histochemical examination. Dermatan sulfates, chondroitin sulfates (A and/or C) and hyaluronan were localized in the extracellular matrix of the synovial intima, whereby dermatan sulfates were confined to the fibrous component, whereas chondroitin sulfates and hyaluronan were found in the interfibrous matrix. Heparan sulfate was the only notable GAG molecular species localized in the basement membrane of the capillary wall. It is obvious that differences in the quality and localization of glycosaminoglycans in the canine synovial tissue are of specific interest in understanding normal functions as well as pathological alterations of the knee synovium in mammals.

Animals↗

A zymogel enhances the self-cleaning abilities of the skin of the pilot whale (Globicephala melas).

Enzyme activity in the stratum corneum of the pilot whale Globicephala melas was investigated employing colorimetric enzyme screening assays combined with NATIVE PAGE, size exclusion chromatography (SEC) and histochemical staining procedures. Applying different substrates, several enzymes were detected. The histochemical demonstration of some selected hydrolytic enzymes enriched in the stratum corneum showed high extracellular accumulation. As demonstrated by size exclusion chromatography, high molar mass aggregates were built up from a glycoprotein-rich 20-30-kD fraction. Using NATIVE PAGE experiments under non-reducing conditions, a selection of five degrading enzymes was recovered within the above-reported aggregates. Activity of extracellular aggregate-attached enzymes in the superficial layer of the stratum corneum exhibited no remarkable decrease potentially resulting from self-degradation. We thus conclude that due to their enclosure within the microenvironment of aggregates, a zymogel is formed and autolysis of the stratum corneum is reduced. With respect to the skin surface, the zymogel with hydrolytic activities covering major parts of it enhances the self-cleaning abilities of the skin of the pilot whale based on physical pre-requisites by hydrolyzing adhesive glycoconjugates of settling biofouling organisms considered as primary steps in fouling.

Animals↗

The nitric oxide donor pentaerythritol tetranitrate can preserve endothelial function in established atherosclerosis.

Recent results suggested that long-term treatment with a low dose of the organic nitrate pentaerythritol tetranitrate (PETN, 6 mg kg(-1) per day) for 16 weeks slightly decreases aortic superoxide production in normal rabbits. We sought to determine if PETN can preserve endothelium dependent relaxation (EDR) in atherosclerotic rabbits. Three groups of 9 - 10 New Zealand White rabbits received a cholesterol chow (0.75%) for 16 weeks. One group (CHOL16) served as control and two groups were fed for another 16 weeks a cholesterol-chow without (CHOL32) or with 6 mg PETN kg(-1) per day (PETN32). Isolated aortic rings of CHOL16 showed a typical impairment of EDR with a maximal relaxation at 1 microM acetylcholine of 28+/-16%. In CHOL32-rings EDR was completely impaired. In striking contrast, EDR in PETN32 (24+/-15%) was similar to that of CHOL16 indicating a protective effect of PETN on endothelial function. Vascular superoxide production measured with the lucigenin method was not different between the groups. Aortic lesion formation in PETN32 was smaller than in CHOL32 (P<0.008). The onset of copper-induced LDL-oxidation (lag-time) after 16 weeks of cholesterol feeding (214+/-9 min) was reduced in CHOL32 (168+/-24 min, P=0.035) but not in PETN32 (220+/-21 min). This indicates prevention of increased LDL oxidation by PETN. The halfmaximal effective vasodilator concentrations of PETN (in -logM) were identical in CHOL16 (7.9+/-0.1), CHOL32 (7.6+/-0.2) and PETN32 (7.7+/-0.2). Similar results were obtained with S-nitroso-N-acetyl-D,L-penicillamine. These data suggest that PETN can reduce the progression of lesion formation, endothelial dysfunction and of LDL-oxidation in established atherosclerosis.

Animals↗

p21/waf1/cip1 in gastric cancer: associations with histopathological subtypes, lymphonodal metastasis, prognosis and p53 status.

BACKGROUND: Cyclins and cyclin-dependent kinases are determining factors of the cell cycle. In the present study, we investigated the role of p21 and p53 in the biology of gastric cancer, focusing on its influence on progression and prognosis (n = 195). METHODS: P21 and p53 immunoreactivity was analysed immunohistochemically, applying monoclonal antibodies. The p53 status was comparatively evaluated by PCR-SSCP analysis of p53 mutations in selected tumours. RESULTS: Fifty-eight percent of the carcinomas were p21+ in more than 5% of the cancer cell nuclei, whereas 19% exhibited a p21 immunoreactivity in more than 20% of the nuclei. On the other hand, p53 was over-expressed (in more than 50% of the nuclei) in about 45% of the specimens. P21 immunoreactivity in more than 5% of the nuclei was inversely related to the pN as well as pTNM cancer stage, whereas only a strong p21 expression (in >20% of the nuclei) was correlated with a better survival probability in a univariate analysis. The p53 status was associated with lymphonodal metastasis, but not with prognostic data. In multivariate survival analyses, neither p21 nor p53 emerged as independent prognostic factors. Compared with the results of p53 mutation analysis by PCR-SSCP. p21 immunoreactivity was reduced in p53-mutated cases. CONCLUSIONS: These features show an association of p21 over-expression with certain clinico-pathological parameters of gastric cancer. In this context, our data suggest that p21 immunoreactivity in more than 5% of the tumour cells has a predictive value for the course of adenocarcinoma of the stomach.

Adenocarcinoma↗

PCR fingerprinting: a convenient molecular tool to distinguish between Candida dubliniensis and Candida albicans.

Candida dubliniensis was recently identified as a germ-tube- and chlamydospore-positive yeast, phenotypically and morphologically indistinguishable from the phylogenetically closely related yeast species C. albicans and its synonymized variant C. stellatoidea. The high similarity between these yeast species causes significant problems in the correct identification of C. dubliniensis in a standard clinical mycology laboratory. Polymerase chain reaction (PCR) fingerprinting was successfully applied here to distinguish between clinical isolates of the two closely related species. Microsatellite ([GACA]4) and minisatellite ([5'-GAGGGTGGCGGTTCT-3'], derived from the core-sequence of the wild-type phage M13) specific oligonucleotides were used as single primers in PCR to amplify hypervariable inter-repeat DNA sequences from 16 C. dubliniensis strains and 11 C. albicans strains. Each species, represented by its ex-type strain, could be identified by a distinct species-specific multilocus pattern, allowing identification to species level for all clinical isolates. In addition, the PCR fingerprinting generated strain-specific profiles, making this method applicable to epidemiological investigations. PCR fingerprinting using the primer M13 is proposed here as a simple, reliable and highly reproducible molecular tool to differentiate between strains of C. albicans and C. dubliniensis.

Candida↗

Partial sequence analysis of the actin gene and its potential for studying the phylogeny of Candida species and their teleomorphs.

The actin gene has been studied as a potential phylogenetic marker for selected members of the anamorphic genus Candida and seven related teleomorphic genera (Debaryomyces, Issatchenkia, Kluyveromyces, Saccharomyces and Pichia from the Saccharomycetaceae; Clavispora and Metschnikowia from the Metschnikowiaceae). The nucleotide sequences of 36 fungal taxa were analysed with respect to their molecular evolution and phylogenetic relationships. A total of 460 bp (47%) of the coding 979 bp were variable and 396 bp (40%) of these were found to be phylogenetically informative. Further analysis of the sequences showed that the genic G+C contents were higher than the nuclear G+C contents for most of the taxa. A strong positive correlation was found between G+C content over all codon positions and third positions. First and second codon positions were considered to be independent of the genic G+C content. The expected transition/transversion bias was detected only for third positions. Pairwise comparisons of transitional and transversional changes (substitutions) with total percentage sequence divergences revealed that the third position transitions showed no saturation for ingroup comparisons. A specific weighting scheme was set up, combining codon-position weights with change-frequency weights to enable the inclusion of distant outgroup taxa. Parsimony analyses of the investigated taxa showed four groups, three of which corresponded to major clusters that had been established previously in Candida by rDNA analysis. Interrelationships among the species groups in this heterogeneous anamorphic genus were determined. The polyphyletic origin of the selected Candida species and their close associations with several ascomycete genera were verified and known anamorph/teleomorph pairs confirmed. The actin gene was established as a valuable phylogenetic marker with the particular advantage of an unambiguous alignment.

Actins↗

Cytological and lectin histochemical characterization of secretion production and secretion composition in the tubular glands of the canine anal sacs.

The study reports on secretion production and composition in the tubular glands of the canine anal sacs. For this purpose, light and electron microscopical (TEM, SEM) as well as several histochemical methods for the demonstration of lysosomal acidity, lipofuscin, and complex carbohydrates were used. The glandular tubules exhibited a pseudostratified epithelium with secretory cells of a different shape as related to secretion production activity, and regionally varying amounts of basal cells. Flat, cuboidal or columnar cells with or without apocrine-like protrusions were assembled in one glandular endpiece, although grouping of these cell types often occurred. Active secretory cells were columnar with many cytoplasmic vesicles and a typically merocrine and/or micro-apocrine exocytosis of vesicle contents. Additionally, many lysosomes of different sizes could be found, whereby in aged cells giant secondary lysosomes (autophagolysosomes, about 7 microm in diameter) occupied the major cell part. These giant lysosomes were shed by an apocrine-like process forming a final bottleneck stage of the upper cell part, and consisted of ceroid-type lipofuscin. The general carbohydrate histochemical and the lectin histochemical methods revealed that the secretion produced was composed of strongly concentrated neutral glycoproteins with the following saccharide residues: alpha-D-mannose, beta-D-galactose, beta-N-acetyl-D-glucosamine, alpha-L-fucose and N-acetyl-neuraminic acid (sialic acid); the luminal secretion contained only beta-D-galactose and, especially, N-acetyl-neuraminic acid. This luminal secretion showed a spatially orientated maturation beginning in terminal tubular regions and finishing near the excretory duct, independent of the different secretory cell types. The results obtained demonstrated highly active secretion production, with a regional variation in the glandular tubule, and at least three different modes of secretion by the secretory cells, whereby the shedding of giant lipofuscin granules seems to be very specific. The high amounts of sialic acids in the glycoproteins found may influence the rheological properties of the secretion by their water-binding capacities.

Anal Sacs↗

TEM and SEM observations on the extracellular matrix of the developing murine centra.

TEM and SEM application demonstrated that the shift from chondrification to ossification in the developing murine centra from day 15 to day 18 of gestational age is marked by typical structural variations of the extracellular matrix (ECM). During day 15 GA, typical matrix vesicles with crystalline contents appeared, as followed by single and fusing pleomorphic aggregates of a more regular crystalline structure. During days 17/18 GA, these structures disappeared, and the ECM now exhibited a network of collagen fibrils that had been less conspicuous before. During the time period studied, the ECM switched from a more acid (proteoglycans) to a rather neutral (glycoproteins) milieu.

Animals↗

Distribution of tissue kallikrein in the integumental blood vessel system of wild mammals.

The study demonstrates tissue kallikrein with the help of a very sensitive immunohistochemical B-SA method in smooth muscle cells and myocytes / pericytes of the wall of subepidermal arterioles and capillaries of 17 mammalian species from 6 different orders. Positive immunoreactions could also be detected in the wall of blood vessels near to and between hair follicles and skin glands. The reaction staining in subepidermal blood vessels was particularly distinct in animals with a vital epidermis that was significantly thicker than 20 microm. The results obtained are discussed with special regard to the general skin biology of the wild mammals studied, considering comparative hair coat density and normal hazards to the integument.

Animals↗

Helicity dependence of gammap --> Npi below 450 MeV and contribution to the Gerasimov-Drell-Hearn sum rule.

The helicity dependence of the single pion photoproduction on the proton has been measured in the energy range from 200 to 450 MeV for the first time. The experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a circularly polarized, tagged photon beam, and a frozen-spin target. The data obtained provide new information for multipole analyses of pion photoproduction and determine the main contributions to the Gerasimov-Drell-Hearn sum rule and the forward spin polarizability gamma(0).

Journal Article↗

Aspects of general antimicrobial properties of skin secretions in the common seal Phoca vitulina.

Considerable amounts of several saccharide residues (alpha-D-Man, beta-D-GlcNAc, alpha-D-GalNAc, beta-D-Gal, alpha-D-Gal, alpha-L-Fuc, NeuNAc) are demonstrated by lectin histochemistry in the sections of the sebaceous glands, and, particularly, the apocrine tubular glands of the common seal. These sugars may be liberated on the skin surface by microbial activities and, then, represent a general antimicrobial protection mechanism of the skin because of their ability to inhibit the adherence of different bacteria and fungi to the epidermis.

Animals↗

[Portal vein resection in the framework of surgical therapy of pancreatic head carcinoma: clarification of indication by improved preoperative diagnostic procedures?].

Tumor invasion of the portal vein by ductal adenocarcinoma of the pancreatic head is classically known as a criterion for inoperability. Despite improvement in operation techniques for portal vein resection during Whipple's procedure and acceptable mortality and morbidity, in the case of uncertain tumor infiltration vascular resection cannot be recommended in general. The problem is the preoperative detection of tumor infiltration of the portal vein. Often the surgeon is confronted with unsuspected macroscopic portal vein infiltration or tumor adhesion during the operation. Between 1986 and 1995 105 patients underwent Whipple's procedure for ductal adenocarcinoma of the pancreatic head in our department. In eight of these cases partial portal vein resection was performed because of macroscopic tumor infiltration or tumor adhesion. In all eight cases the preoperative diagnostic procedures with CT and portography did not show any suspicion of tumor infiltration. In four of the eight cases histological tumor infiltration of all vascular layers was found. In the others we found no or only adventitial tumor invasion. The patients without tumor infiltration of the portal vein showed a survival time after surgery of 27.78 months in contrast to 6.67 months in the group with histologically proven tumor infiltration. Endovascular, intraportal ultrasound (IPEUS), a new diagnostic procedure, can give helpful information regarding portal vein involvement. Although the IPEUS is not a standard diagnostic procedure it was shown to detect portal vein infiltration with high sensitivity and specificity. Our results indicate that in such cases where portal vein infiltration has been excluded by IPEUS, patients with macroscopic tumor adhesion do benefit from partial portal vein resection.

Adult↗

Prognostic factors in the operative treatment of ductal pancreatic carcinoma.

BACKGROUND AND AIMS: The average 5-year survival rate following resection of a ductal adenocarcinoma of the pancreas is 10%, worldwide. Despite increasing resection rates, only about 20% can be operated on with curative intent. A differential histopathological analysis of the resected tumors may help to justify expanding the surgical procedure by extended lymph-node dissection. PATIENTS/METHODS: Between January 1986 and December 1995, a total of 113 patients underwent resection with curative intent for a ductal pancreatic carcinoma with regional lymph-node dissection. All histological findings were reviewed and reclassified in accordance with the 1997 Union Internationale Contra la Cancrum (UICC) classification. Survival data for all of these patients were obtained from family doctors and registration offices. Independent prognostic factors were statistically analyzed. RESULTS: Of the 113 patients, 93 received an R0 resection. The postoperative mortality rate was 2.2% (2 of 93). More than one-half of the tumors had a diameter of between 2.1 cm and 4 cm. Among the 22 tumors measuring up to 2 cm in diameter, 41% already had lymph-node metastasis and 86% invasion of the lymphatic vessels. Carcinomas measuring between 4.1 cm and 6 cm were all associated with lymph-vessel invasion. Perineural invasion was present in 50% of the tumors. A noteworthy finding was the fact that 64% of the 25 tumors with negative lymph nodes had lymph-vessel invasion, and 48% perineural invasion. The cumulative 5-year survival rate of the R0-resected patients was 10. 5%. Patients with lymph-node-negative stages survived significantly longer (26.5%) than patients with lymph-node-positive stages (5%). Furthermore, a significant difference was seen between pN1a and pN1b (16.7% vs 2.2%). Multivariate analysis identified tumor grading, tumor size and lymph vessel invasion as independent prognostic factors. CONCLUSIONS: Apart from the factors tumor size and tumor grading, lymph-vessel invasion appears to be of special significance for the long-term prognosis. Already in the pN0 stage, the latter was present in 64% of the cases and must be considered a precursor of lymphogenic metastasization. Since lymph-vessel invasion was demonstrated in 86% of tumors measuring less than 2 cm, the therapeutic consequence for all ductal pancreatic tumors is an extended lymphatic and soft tissue dissection that goes beyond the regional lymph-node stations.

Aged↗