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Biomedical subjects

W Meyer

Publications and source records attributed to W Meyer.

At least 181 records · Page 10Linked to original sources

Feasibility and limitations of a cytometric DNA ploidy analysis procedure in tissue sections.

To produce IOD histograms from tissue sections interpretable in terms of DNA ploidy, compromises between section thickness, nuclear volume and cellularity have to be found. In most cases, some kind of correction for capping effects will be inevitable. One of the correction procedures for that purpose was studied, i.e. that concerning the extent of errors which are necessarily introduced by assuming a distributional model of nuclei in the tissue slide. This procedure is mainly based on the assumptions of a spherical shape of the nuclei, of their homogeneous chromatin distribution, and of an equal distribution of the equatorial plane inside the tissue slide sectioned. Measurements on rat liver sections with a series of section thicknesses demonstrated that the correction procedure would lead to an exact position of the IOD peaks from the tetraploid nuclei on the ploidy axis. The width of the IOD peaks will not be diminished considerably as compared to uncorrected IOD histograms. Therefore, there are serious limitations to the procedure as compared to the DNA ploidy analysis on smears or imprints. If applied very critically in the case of tissue sections, the method may provide additional information about the DNA ploidy in those cases which lack a uniform tumour cell population or adequate material for smear preparations.

Animals↗

Arrangement of elastic fibres in the integument of domesticated mammals.

The hairy skin of important domesticated mammals (12 species) was studied with scanning electron microscopy, transmission electron microscopy, laser scanning microscopy, and several light microscopical methods, to obtain more information about three-dimensional elastic fibre arrangement. It was obvious that there is a basic construction scheme of the elastic fibre meshwork as present in the upper and mid-dermis, with special regard to the size, number, and grouping of hair follicles. In the densely-haired species, in particular, a typical elastic mat with horizontal fibres is formed. In many of the sparsely-haired animals, the upper and mid-dermis show a sponge-like elastic system. In the rather massive, collagen-rich skin of large species, the lower two thirds of the dermis without hair follicles only possess a loosely-structured elastic network, but thick elastic sheets are found at the border zone with the hypodermis. Specific features appear with regard to the type of mechanical strain exerted, different body regions, varying hair follicle density, or as connected with the anchoring of the hair follicle complex, blood vessels, and nerves.

Animals↗

[Determination of prognosis-relevant factors in patients with hypo- or oropharyngeal carcinoma].

The influence of pathomorphological parameters (keratinization, grading, nucleolar organizer region (NOR) counts, automatic analysis of micrographs) on prognosis was determined for 284 patients with carcinomas of the oropharynx or hypopharynx. Keratinization was found to have no influence on prognosis. Histopathological grading and automatic analysis of micrographs with mark 22 were seen to be of major relevance. Patients with grading 3 were noted to have a poorer prognosis than those with gradings of 1 or 2. This latter finding was statistically significant. Although the absolute NOR counts had no influence on prognosis, they did show a statistically significant effect on the extent of lymphogenic formation of metastases. Cox regression analysis of clinical and pathomorphological parameters revealed that combination therapy, tumor grading, and mark 22 of automatic analysis of micrographs were important factors relevant to prognosis.

Biomarkers, Tumor↗

[Microscopic studies of the skin of Turkish angora goats. III. Cyclic annual growth of the sebaceous glands and hypodermis].

The study describes circannual variations of growth in sebaceous glands and hypodermis. The results have been obtained by light microscopical and lipid histochemical methods. The sebaceous glands showed high secretory activities during the summer months, obviously as related to increasing fibre lengths. The hypodermis was thickest by fat accumulation during summer, as probably connected with high growth rates of the hair follicles. The findings are discussed with regard to the general, seasonally varying feeding conditions of goats in Central Anatolia. A direct relation between diet quantity and quality, and fleece quality is postulated.

Animals↗

[The physician's cognition during cardiopulmonary resuscitation of the human].

The cognitions of 20 emergency-physicians while working on a mobile resuscitation unit were examined by means of questionnaire in over 260 situations of resuscitation. A pattern of cognitions could be detected: Emergency physicians appear not to think very much during resuscitation. If there are thoughts, these usually concern the obvious, or what is immediately present in the situation, i.e. the patient or the patient's relatives; repression may also play a role. Cognitions which are reflective of self are rare and only develop late in the situation, depending on the surroundings and the amount of stress. The cognitions concerning the relatives are frequent in those situations with direct physician-relative contact. The physicians often report in retrospect having felt compelled to a decision for resuscitation by the presence of the relatives; nevertheless, the decision itself appears to be a result, rather, of their cognitions of the relatives. Distancing by means of cognition was ubiquitously employed as a coping strategy by physicians when in situations which were perceived as not having a positive outcome. Thoughts about "own death" or "about the patient" are specific, however, for certain groups of doctors. Results of the present investigation suggest that physicians have cognitions about relatives during the process of decision making, and cognitions about the patient during the resuscitation manoeuvre.

Adult↗

Demonstration of NADPH-diaphorase (NO-synthase) in the apocrine and eccrine skin glands of domesticated mammals.

The study demonstrates a strong enzyme histochemical and immunohistochemical reaction staining for NADPH-diaphorase/NO-synthase in the secretory cells of the apocrine glands in the hairy skin, and the eccrine glands in the foot pads of domesticated mammals. The results obtained are discussed in view of a regulatory action of the NO generated by these enzyme activities, implying a direct influence of NO on the contractile properties of glandular myoepithelial cells. In this way, a basic and simple mechanism to couple secretion production and secretion extrusion can be proposed.

Animals↗

Influence of endothelium and nitrovasodilators on free thiols and disulfides in porcine coronary smooth muscle.

It is hypothesised that the well known development of tolerance to the vasodilating action of organic nitrates is contributed by intracellular depletion of free thiols occurring during repeated treatment with these drugs. Therefore, ring segments of porcine coronary arteries with and without endothelium were treated for 30 min with either vehicle or 100 microM of isosorbide-5-mononitrate, glyceryl trinitrate, S-nitroso-N-acetyl-D,L-penicillamine or N-(3-nitratopivaloyl)-1-cysteine-ethylester (SPM 3672), and the content of histochemically stained free thiols (-SH) and disulfides (S-S-) was measured densitometrically in single smooth muscle cells. In the presence of endothelium the content of -SH in smooth muscle cells of controls (n = 8) gave an extinction of 0.127 +/- 0.013 in the intima and 0.120 +/- 0.010 in the media. The corresponding values for S-S- were 0.684 +/- 0.084 and 0.535 +/- 0.120 (n = 8). Removal of endothelium reduced S-S- to 82.1 +/- 70% and increased -SH to 126.7 +/- 6.7%. Treatment with all nitrates reduced -SH in intact artery segments to a similar degree, ranging between 54.0 +/- 4.4 and 68.7 +/- 4.7% (n = 8-10). In contrast, S-S- content was less affected and reached values between 70.6 +/- 2.8 and 91.6 +/- 6.0% (n = 8-9). As evaluated by tension studies, tolerance developed for glycerol trinitrate and isosorbide-5-mononitrate but not for S-nitroso-N-acetyl-D,L-penicillamine. Induction of tolerance with glycerol trinitrate (0.1 mM) produced a significantly more pronounced attenuation in activity of isosorbide-5-mononitrate than tolerance induction with isosorbide-5-mononitrate (1 mM). In contrast, the potency of SPM 3672 was not reduced in glycerol trinitrate-tolerant arteries. We conclude that, in porcine coronary arteries, an intact endothelium modifies intracellular thiols and disulfides. In addition, nitrate tolerance is associated with, but probably not caused by, thiol depletion.

Analysis of Variance↗

Rapid identification and differentiation of yeasts by DNA and PCR fingerprinting.

We have used the techniques of DNA fingerprinting and polymerase chain reaction (PCR) with probes specific for hypervariable repetitive DNA sequences (mini- and microsatellite DNAs) to analyze 36 yeast strains belonging to 10 species and 2 genera. Using (GTG)5, (GACA)4, phage M13 DNA and the M13 sequence GAGGGTGGCGGTTCT as probes and primers, respectively, we obtained DNA polymorphisms which allowed us to discriminate 23 biotechnologically important strains of the yeast Saccaromyces cerevisiae and to distinguish them from strains of S. pastorianus, S. bayanus and S. willianus. Our results demonstrate that both DNA and PCR fingerprinting are suitable tools for an easy, fast and reliable molecular typing of yeasts. The DNA fingerprinting method seems to be more sensitive than PCR fingerprinting with respect to the individualization of strains. Nevertheless, using the PCR fingerprinting technique we were able to unambigously discriminate between genotypes of different species. Therefore, PCR fingerprinting might become a useful tool in the classification of yeasts on the basis of phylogenetic relatedness.

Base Sequence↗

DNA- and PCR-fingerprinting in fungi.

DNA-fingerprinting has been successfully used to detect hypervariable, repetitive DNA sequences (minisatellites and microsatellites) in fungi. Combined with methods used to identify random amplified polymorphic DNA (RAPD), conventional DNA-fingerprinting hybridization probes can also be used as single primers to detect DNA polymorphisms among fungal species and strains. The oligonucleotides (CA)8, (CT)8, (CAC)5, (GTG)5, (GACA)4 and (GATA)4, as well as the phage M13 and its core sequence, have been used as specific probes in hybridization experiments and as primers for PCR analysis. Both methods have enabled the differentiation of all the fungal species and strains that were examined, including species of Penicillium, Trichoderma, Leptosphaeria, Saccharomyces, Candida and Cryptococcus. These methods have been used 1) to clarify the taxonomic relationships among relevant species of the Trichoderma aggregate, 2) to discriminate between aggressive and non-aggressive isolates of the rape seed phytopathogen, Leptosphaeria maculans, and 3) to identify strains of the pathogenic yeasts, Cryptococcus neoformans and Candida albicans. PCR-fingerprinting allowed serotypes of C. neoformans to be distinguished. The application of DNA- and PCR-fingerprinting to fungal DNA should aid in clarification of their taxonomy and improved diagnosis of mycotic disease.

Base Sequence↗

Lectin histochemical study of early postnatal vascularization of the developing pars distalis adenohypophysis of the gray short-tailed opossum (Monodelphis domestica, Marsupialia).

Individuals from 18 litters between 0.5 day and 13 days post partum, and two adult specimens of Monodelphis domestica (Marsupialia), were studied by TEM and lectin histochemistry. Positive reactions for PO-lectins in the developing pituitary were found in the vascular and/or perivascular elements; secretory cells did not react. Positive vascular reactions varied with both the type of lectin and the age of the developing animal. In the adults, the reactions were reversed: there were no vascular, but a variety of positive cellular reactions. It is concluded that the adenohypophyseal blood vascular system is very far from being complete and mature in the newborn M. domestica. According to specific data taken from the literature, the lectin histochemistry indicates a sequential appearance of several components of the extracellular matrix, suggesting also that the actively organ-invading capillaries may be a good model for the study of basement membrane development.

Aging↗

High selectivity for inhibition of phosphodiesterase III and positive inotropic effects of MCI-154 in guinea pig myocardium.

MCI-154 (0.3-100 microM) exerted a concentration-dependent positive inotropic effect in isolated guinea pig papillary muscles (EC50 0.8 microM). The efficacy of MCI-154 (253% of predrug value) was 1.7-fold higher than that of saterinone but comparable to that of milrinone. Carbachol markedly reduced the increase in force of contraction (FOC) of MCI-154. In intact contracting papillary muscles, the positive inotropic effect was accompanied by an increase in cyclic AMP content to 0.78 +/- 0.09 pmol/mg wet weight (n = 10), corresponding to 150% of the basal value (0.51 +/- 0.05 pmol/mg wet weight, n = 21) in the presence of submaximal cyclic AMP phosphodiesterase (PDE) isoenzyme III inhibiting concentrations of MCI-154 (30 microM). MCI-154 (1-1,000 microM) concentration-dependently inhibited the activity of PDE III from homogenates of guinea pig myocardium. The IC50 was 3.8 microM. PDE I, II, and IV were not significantly affected up to 100 microM (PDE I and IV) and up to 1,000 microM (PDE II). In comparison, milrinone and saterinone were PDE III/IV-selective PDE inhibitors. Rolipram inhibited PDE IV only. IBMX and theophylline were nonselective PDE inhibitors. MCI-154 had only a marginal positive chronotropic effect. The frequency of spontaneously beating right auricles from guinea pig heart was increased by 8.7% at most (n = 5). MCI-154 increased Ca2+ sensitivity in chemically skinned porcine ventricular muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hybridization probes for conventional DNA fingerprinting used as single primers in the polymerase chain reaction to distinguish strains of Cryptococcus neoformans.

In conventional DNA fingerprinting, hypervariable and repetitive sequences (minisatellite or microsatellite DNA) are detected with hybridization probes. As demonstrated here, these probes can be used as single primers in the polymerase chain reaction (PCR) to generate individual fingerprints. Several conventional DNA fingerprinting probes were used to prime the PCR, yielding distinctive, hypervariable multifragment profiles for different strains of Cryptococcus neoformans. PCR fingerprinting with the oligonucleotide primers (GTG)5, (GACA)4, and the phage M13 core sequence (GAGGGTGGXGGXTCT), but not with (CA)8 or (CT)8, generated DNA polymorphisms with all 42 strains of C. neoformans investigated. PCR fingerprints produced by priming with (GTG)5, (GACA)4, or the M13 core sequence differentiated the two varieties of C. neoformans, C. neoformans var. neoformans (serotypes A and D) and C. neoformans var. gattii (serotypes B and C). Furthermore, strains of serotypes A, D, and B or C could be distinguished from each other by specific PCR fingerprint patterns. These primers, which also successfully amplified hypervariable DNA segments from other species, provide a convenient method of identification at the species or individual level. Amplification of polymorphic DNA patterns by PCR with these primers offers several advantages over classical DNA fingerprinting techniques, appears to be more reliable than other PCR-based methods for detecting polymorphic DNA, such as analysis of random-amplified polymorphic DNA, and should be applicable to many other organisms.

Base Sequence↗

Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors.

PURPOSE: The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors. PATIENTS AND METHODS: To reduce interpatient variability in carboplatin systemic exposure, 45 children were treated with doses individualized to a target area under the serum concentration versus time curve (AUC) based on renal function, using technetium 99-diethyl-enetriamine pentaacetic acid (99mTc-DTPA) clearance to estimate glomerular filtration rate (GFR). Cohorts of at least three patients received carboplatin at an initial target AUC of 2 mg/mL x min, with escalations of 1 mg/mL x min in subsequent cohorts. Courses consisted of carboplatin on day 1 followed by IFOS 2 g/m2 plus VP-16 100 mg/m2 on days 2 and 3. Patients received at least two courses, with a maximum of eight courses possible in the absence of progressive disease. When only moderate toxicity occurred after escalation to 5 mg/mL x min, a third dose of IFOS plus VP-16 was added. After three patients were treated at this level, carboplatin escalation proceeded. RESULTS: Neutropenia and thrombocytopenia were the dominant toxicities in the 43 assessable patients. At the target AUC of 8 mg/mL x min, 13 of 20 cycles were associated with febrile neutropenia. For phase II trials, we recommend a carboplatin target AUC of 6 mg/mL x min with three doses of IFOS and VP-16 for patients with prior craniospinal irradiation or high-dose cisplatin (CDDP)/VP-16, or 7 mg/mL x min for patients without such histories. There were two complete responses (CRs), 13 partial responses (PRs), and 17 objective responses (ORs). CONCLUSION: The ICE regimen shows promising activity in pediatric solid tumors. The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy.

Adolescent↗

Effects of the alpha 1-adrenoceptor agonist phenylephrine in pig heart. Study of the direct action on contractile proteins.

The effects of the alpha 1-adrenoceptor agonist phenylephrine (CAS 59-42-7) on Ca++ sensitivity of the contractile proteins and on force of contraction of the heart were studied in right ventricular preparations isolated from pigs. In contracting trabeculae phenylephrine (3-100 mumol/l) increased force of contraction in the presence of propranolol maximally by 91.8 +/- 36.2% (n = 5). The effect of phenylephrine was antagonized by prazosin, indicating an alpha-adrenoceptor-mediated positive inotropic effect. Glycerol- and Lubrol WX-extracted trabeculae ("chemically skinned") were activated by Ca(++)-concentrations between 0.01 and 47.7 mumol/l. Phenylephrine (0.1-100 mumol/l) did not affect the Ca++ activated force in these preparations. A direct intracellular action of phenylephrine on contractile proteins is thus rather unlikely to contribute to the positive inotropic effect of phenylephrine.

Adrenergic alpha-Agonists↗

Carbohydrate histochemistry of skin glands in the Turkish Angora goat.

The skin glands of the general body surface of the Turkish Angora goat were studied by means of selected carbohydrate histochemical methods, in particular several PO-lectin procedures. Both gland types exhibited intensive secretion production, irrespective of season and body region. The different histochemical staining procedures demonstrated that glycoconjugates, especially neutral glycoproteins are present in the secretory cells and secretion products of the apocrine glands. The peroxidase (PO)-lectin-procedures indicated the following saccharide residues: alpha-D-mannose, N-acetyl-beta-D-glucosamine, alpha-D-glucose, N-acetyl-D-galactosamine, beta-D-galactose, alpha-D-galactose, and alpha-fucose, including small amounts of N-acetylneuraminic acid and N-glycolylneuraminic acid. Relatively large amounts of glycoconjugates, probably also glycolipids, were found in the peripheral cells and the sebum of the sebaceous glands, exhibiting the following saccharide residues: N-acetyl-D-galactosamine, alpha-fucose, N-acetylneuraminic acid and N-glycolylneuraminic acid. The results obtained are discussed as related to findings from corresponding studies in other mammalian species. The secretory substances present obviously create a clearly alkaline pH milieu within the fleece of the Angora goat. Such conditions are also known to exist, for example, in the Merino sheep fleece.

Animals↗