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Biomedical subjects

A Meyer

Publications and source records attributed to A Meyer.

At least 19 recordsLinked to original sources
PubMed1995

Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line.

We report the cloning and characterization of a novel basophil CC chemokin receptor, K5-5, from the human immature basophilic cell line KU-812. The predicted protein sequence of K5-5 shows only 49% identity to the macrophage inflammatory protein-1 alpha/RANTES receptor (CC CKR-1) and 47% identity to monocyte chemotactic protein-1 receptor (b form), suggesting that this cDNA encodes a novel member of the CC chemokine receptor family. Analysis of K5-5 mRNA expression indicates that it is restricted to leukocyte-rich tissues. In addition, we have shown significant levels of K5-5 mRNA in human basophils, which were up-regulated by treatment with interleukin-5. The CC chemokines, Macrophage inflammatory protein-1 alpha, RANTES, and monocyte chemotactic protein-1 were able to stimulate a Ca(2+)-activated chloride channel in Xenopus laevis oocytes injected with K5-5 cRNA, whereas no signal was detected in response to monocyte chemotactic protein-2, macrophage inflammatory protein-1 beta, or the CXC chemokine, interleukin-8. Taken together, these results indicate for the first time the presence of a CC chemokine receptor on basophils, which functions as a "shared" CC chemokine receptor and may therefore be implicated in the pathogenesis of basophil-mediated allergic diseases.

Amino Acid Sequence↗
PubMed1995

Pharmacokinetics of orally administered cyclosporine in patients with Crohn's disease.

Cyclosporine pharmacokinetics were reported to be influenced in patients with Crohn's disease. To explore the relationship between Crohn's disease and cyclosporine pharmacokinetics, this investigation was performed in 20 patients with varying Crohn's Disease Activity Index (CDAI). A single oral dose of 300 mg of cyclosporine was given and serial blood samples were obtained over 52 hours. Cyclosporine whole blood concentrations were determined by a specific monoclonal radioimmunoassay. Pharmacokinetic parameters were comparable with those of healthy volunteers. No statistically significant difference between the pharmacokinetic parameters of the patients with CDAI values less than 150 and those with CDAI values 150 or greater could be shown. Although several factors associated with the pathology of Crohn's disease theoretically could influence the pharmacokinetics of orally administered cyclosporine, this investigation did not identify statistically significant differences in cyclosporine pharmacokinetics in Crohn's disease patients with different disease activities or different localization of inflammation as compared with healthy volunteers. However, if large parts of the small bowel were removed, a decrease of absorption of cyclosporine could be observed. In any case, it is important to be aware of the clinical variability of Crohn's disease and its potential implications in cyclosporine absorption.

Administration, Oral↗
PubMed1995

Phylogenetic analysis of the South American electric fishes (order Gymnotiformes) and the evolution of their electrogenic system: a synthesis based on morphology, electrophysiology, and mitochondrial sequence data.

The order Gymnotiformes (South American electric fishes) is a fascinating assemblage of freshwater fishes that share the unusual ability to produce and sense electric fields used for electrolocation and social communication. In the last few decades, the electrogenic and electrosensory systems (EES) of these fish have served as an excellent model to study motor and sensory physiology in vertebrates. In an attempt to the evolution of characters associated with the EES in the group, we applied maximum-parsimony (MP), minimum-evolution (ME), and maximum-likelihood (ML) methods to analyze 302 aligned bases of the mitochondrial 12S rRNA and 416 bases of the mitochondrial 16S rRNA of 19 gymnotiform genera representing all six recognized families. Six catfish genera (order Siluriformes) were also sequenced and used as outgroups. The phylogenetic hypothesis resultant from molecular data analysis differs in some respects from previous hypotheses based on morphological studies. Our results were most informative within the family level, as we were unable to elucidate the relationships among deeper branches in this order with sufficient confidence by using molecular data alone. The phylogenetic information of both mitochondrial DNA segments appears to be affected by functional constraints, and the resultant topologies were sensitive to different weighting schemes and the algorithm used. Nonetheless, we found unanimous support for the following phylogenetic relationships: (1) the family Sternopygidae is an unnatural group, and Sternopygus is the sole representative of a unique lineage within the order; (2) the family Hypopomidae is not monophyletic; and (3) the order Gymnotiformes is composed of at least six natural clades: Sternopygus, family Apteronotidae, a new clade consisting of the remaining sternopygids, families Hypopomidae + Rhamphicthyidae, family Electrophoridae, and family Gymnotidae. By combining molecular, morphological, and physiological information, we propose a new hypothesis for the phylogeny of this group and suggest a new family Eigenmanniidae n. (order Gymnotiformes).

Animals↗
PubMed1995

Mitochondrial DNA sequences and multiple data sets: a phylogenetic study of phytophagous beetles (Chrysomelidae: Ophraella).

This paper presents the phylogenetic infrastructure for an integrated historical and experimental study of host use evolution in the chrysomelid leaf beetle genus Ophraella. We report the collection of sequence data from the 16S ribosomal RNA (446 bp) and the cytochrome oxidase subunit I (420 bp) mitochondrial genes from 12 species of Ophraella and two outgroups. Sequence analysis revealed a strong A + T nucleotide bias, high interspecific COI sequence divergences (up to 21.4%) that greatly exceeded those for 16S (up to 5.9%), high intraspecific COI divergences (up to 3.8%), a dearth of amino acid substitutions in COI, and differing substitution patterns in ribosomal stems and loops. Intraspecific variation in COI haplotypes generally supported the genealogical coherence of Ophraella lineages, while suggesting two cases of paraphyletic species. Separate phylogenetic analyses of 16S and COI data sets yielded largely congruent trees. A combined 16S + COI analysis yielded a single shortest tree under maximum parsimony that was identical to trees provided by successive approximations, neighbor-joining, and maximum-likelihood methods. This topology proved robust to various forms of weighting and most nodes were highly supported (by bootstrap analysis). Separate parsimony analyses of mtDNA and previously collected morphological and electromorphic data sets revealed congruent estimates of all cladistic relationships except those within one clade. Analysis of the pooled data sets in a combined approach additionally provided support for the basal placement of two species from this clade, although the topology for the remaining species was weakly supported and incongruent with the mtDNA tree. Each data set contained significantly structured phylogenetic signal with respect to this clade, and data sets exhibited limited conflict (character incongruence) with each other. The combined data set, however, was found to lack phylogenetic signal. These observations may imply that pooling heterogeneously evolving classes of data obscured the phylogenetic signal in each, a potential limitation of the combined approach.

Algorithms↗
PubMed1995

Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals.

Idiopathic pulmonary fibrosis (IPF) is characterized by a huge alveolar oxidant burden and a deficiency of glutathione, a major antioxidant, in the pulmonary epithelial lining fluid (ELF). Therefore, a rational therapeutic strategy is to increase lung glutathione to augment the pulmonary antioxidant protective screen. To evaluate this concept, different doses of N-acetylcysteine (NAC), a glutathione precursor, were administered intravenously to eight patients with pulmonary fibrosis and six control subjects. In patients, bronchoalveolar lavage fluid (BALF) total glutathione increased significantly from 0.99 +/- 0.25 microM to 1.79 +/- 0.37 microM within 3 h following 1.8 g NAC, whereas 4.8 g NAC had no additional effect (1.47 +/- 0.34 microM). In the control subjects, NAC did not significantly alter BALF total glutathione (baseline: 0.79 +/- 0.17 microM, 600 mg NAC: 0.92 +/- 0.33 microM, 1.8 g NAC: 1.39 +/- 0.41 microM, 4.8 g NAC: 1.33 +/- 0.46 microM). The same was true in ELF, 1.8 g NAC significantly raised ELF total glutathione in patients from 186 +/- 47 microM to near normal levels (373 +/- 103 microM), with no further increase following 4.8 g NAC (293 +/- 62 microM). In the control subjects, ELF total glutathione remained unchanged independent of the NAC dose (baseline: 342 +/- 91 microM, 600 mg NAC: 385 +/- 135 microM, 1.8 g NAC: 633 +/- 220 microM, 4.8 g NAC: 646 +/- 263 microM). The increases in total glutathione were almost entirely due to increased levels of reduced glutathione, the form functional as an antioxidant. No adverse effects were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1995

[Ischemia of the extremity as a rare complication of alloplastic joint replacement].

Two cases of extremity ischemia after alloplastic knee and hip joint replacement are presented. In both cases early operative intervention led to complete recovery. The mechanisms of iatrogenic vascular injury following arthroplastic operations on the hip and knee joint are demonstrated. In particular, the importance of preexisting vascular occlusive disease is stressed. Diagnostic procedures and implications for treatment are discussed.

Aged↗
PubMed1995

Two in-vivo protocols for testing virucidal efficacy of handwashing and hand disinfection.

Whole-hands and fingerpads of seven volunteers were contaminated with poliovirus type 1 Sabin strain in order to evaluate virucidal efficacy of different forms of handwashing and handrub with alcohols and alcohol-based disinfectants. In the whole-hand protocol, handwashing with unmedicated soap for 5 min and handrubbing with 80% ethanol yielded a log reduction factor (RF) of > 2, whereas the log RF by 96.8% ethanol exceeded 3.2. With the fingerpad model ethanol produced a greater log RF than iso- or n-propanol. Comparing five commercial hand disinfectants and a chlorine solution (1.0% chloramine T-solution) for handrub, Desderman and Promanum, both composed of ethanol, yielded log RFs of 2.47 and 2.26 respectively after an application time of 60 s, similar to 1.0% chloramine T-solution (log RF of 2.28). Autosept, Mucasept, and Sterillium, based on n-propanol and/or isopropanol, were found to be significantly less effective (log RFs of 1.16, 1.06 and 1.52 respectively). A comparison of a modified whole-hand and the fingerpad protocol with Promanum showed similar results with the two systems suggesting both models are suitable for testing the in-vivo efficacy of handwashing agents and hand disinfectants which are used without any water.

Adult↗
PubMed1995

[Lung tumor with unusual metastasis in a cat--a case report].

Metastasis of an adenocarcinoma was diagnosed histologically in a foot pad biopsy of a cat exhibiting progressive locomotion problems, foot pad swelling and nail loosing. A bronchial gland adenocarcinoma was identified as primary tumour at necropsy. Metastases were found in all foot pads, the kidneys and various lymph nodes. A review of the literature and of the own necropsy reports an affinity of bronchial gland carcinoma metastases to skeletal muscles and bones, especially digital bones. Non-respiratory signs as lameness, foot pad swelling and nail loss appear to predominate clinically whereas respiratory signs are observed only in about one third of all cases.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1994

Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from a molecular phylogeny.

Darwin believed that sexual selection accounts for the evolution of exaggerated male ornaments, such as the sword-like caudal fin extensions of male fishes of the genus Xiphophorus, that appear detrimental to survival. Swordtails continue to feature prominently in empirical work and theories of sexual selection; the pre-existing bias hypothesis has been offered as an explanation for the evolution of swords in these fishes. Based upon a largely morphological phylogeny, this hypothesis suggests that female preference to mate with sworded males arose in ancestrally swordless species, thus pre-dating the origin of the sword itself and directly driving its evolution. Here we present a molecular phylogeny (based on mitochondrial and nuclear DNA sequences) of Xiphophorus which differs from the traditional one: it indicates that the sword originated and was lost repeatedly. Our phylogeny suggests that the ancestor of the genus is more likely to have possessed a sword than not, thus questioning the applicability of the pre-existing bias hypothesis as an explanation for the evolution of this sexually selected trait.

Animals↗
PubMed1994

Mitochondrial phylogeny of the Lamprologini, the major substrate spawning lineage of cichild fishes from Lake Tanganyika in eastern Africa.

Lake Tanganyika harbors the oldest, morphologically and behaviorally most diverse flock of cichlid species. While the cichlids in Lakes Malawi and Victoria breed their eggs exclusively by buccal incubation (termed "mouthbrooding"), the Tanganyikan cichlid fauna comprise mouthbrooding and substrate-spawning lineages (fish spawn on rocks, and never orally incubate eggs or wrigglers). The substrate-spawning tribe Lamprologini appears to occupy a key position that might allow one to elucidate the origin of the Tanganyika flock, because five riverine (therefore nonendemic) species from the Zaire River system have been assigned to this tribe, in addition to the lake's endemic species, which make up almost 50% of all 171 species known from this lake (Poll 1986). From 16 species (18 individuals) of the tribe Lamprologini, a 402-bp segment of the mitochondrial cytochrome b gene was sequenced, and, from 25 lamprologine species (35 individuals), sequences from the mitochondrial control region were obtained. To place the Lamprologini into a larger phylogenetic framework, orthologous sequences were obtained from eight nonlamprologine Tanganyikan cichlid species (13 individuals). The Lamprologini are monophyletic, and a clade of six Tanganyikan lineages of mouthbrooders, representing five tribes (Poll 1986), appears to be their sister group. Comparisons of sequence divergences of the control region indicate that the Lamprologini may be older than the endemic Tanganyikan tribe Ectodini, and short basal branches might suggest a rapid formation of lineages at an early stage of the Tanganyika radiation. It is interesting that three analyzed riverine members of the tribe form a monophyletic group; however, they are not the most ancestral branch of the Lamprologini. This might indicate that they are derived from an endemic lamprologine ancestor that left Lake Tanganyika by entering the Zaire River system. These riverine species may not have seeded the Tanganyikan radiation, as currently thought, but may have recently recolonized the river after a long period of isolation, as soon as the lake was connected to the Zaire River again about 2 Mya. Neolamprologus moorii, endemic to Lake Tanganyika, appears to represent the most basal clade of the Lamprologini. Complex breeding behavior, involving the usage of gastropod shells and associated with dwarfism, is likely to have evolved in parallel in several lineages among the Lamprologini. The tribe Lamprologini may be in need of revision, since several genera appear to be polyphyletic.

Animals↗
PubMed1994

Phylogeny of all major groups of cetaceans based on DNA sequences from three mitochondrial genes.

Traditionally, living cetaceans (order Cetacea) are classified into two highly distinct suborders: the echolocating toothed whales, Odontoceti, and the filter-feeding baleen whales, Mysticeti. A molecular phylogeny based on 1,352 base pairs of two mitochondrial ribosomal gene segments and the mitochondrial cytochrome b gene for all major groups of cetaceans contradicts this long-accepted taxonomic subdivision. One group of toothed whales, the sperm whales, is more closely related to the morphologically highly divergent baleen whales than to other odontocetes. This finding suggests that the suborder Odontoceti constitutes an unnatural grouping and challenges the conventional scenario of a long, independent evolutionary history of odontocetes and mysticetes. The superfamily Delphinoidea (dolphins, porpoises, and white whales) appears to be monophyletic; the Amazon River dolphin, Inia geoffrensis, is its sister species. This river dolphin is genetically more divergent from the morphologically similar marine dolphins than the sperm whales are from the morphologically dissimilar baleen whales. The phylogenetic relationships among the three families of Delphinoidea remain uncertain, and we suggest that the two cladogenetic events that generated these three clades occurred within a very short period of time. Among the baleen whales, the bowhead is basal, and the gray whale is the sister species to the rorquals (family Balaenopteridae). The phylogenetic position of beaked whales (Ziphioidea) remains weakly supported by molecular data. Based on molecular clock assumptions, the mitochondrial-DNA data suggest a more recent origin of baleen whales (approximately 25 mya) than has been previously assumed (> 40 mya). This revised phylogeny has important implications for the rate and mode of evolution of morphological and physiological innovations in cetaceans.

Animals↗
PubMed1994

Molecular evolution at subzero temperatures: mitochondrial and nuclear phylogenies of fishes from Antarctica (suborder Notothenioidei), and the evolution of antifreeze glycopeptides.

Most fishes of the perciform suborder Notothenioidei are endemic to the subzero marine waters of Antarctica. A number of remarkable physiological attributes allow them to inhabit this extreme environment; for example, the blood of almost all notothenioid species contains antifreeze glycopeptides. To establish a molecular phylogenetic hypothesis for these fishes, DNA sequences from two mitochondrial genes, portions of the 12S and 16S ribosomal genes (928 base pairs [bp]), were determined for 18 species. These belong to 15 genera in five families of the suborder. The DNA data suggest that two of these families are unnatural groups and consequently that the classification and phylogeny of this suborder is in need of revision. In terms of DNA variation, the Bovichtidae are a distantly related sister group to the other families of the suborder that includes the icefishes, the only vertebrates without hemoglobin. The fishes of the suborder (except the Bovichtidae) seem to have speciated rapidly, forming an adaptive radiation in the Antarctic waters. A phylogenetic analysis of published hemoglobin amino acid sequences for other notothenioid fishes supports these results from mtDNA. On the basis of molecular phylogeny, the evolution of antifreeze glycopeptides was studied. The age of the radiation of notothenioid fishes had been estimated to be at least 38 Mya. However, the level of mtDNA variation detected in notothenioid fishes appears to be too low to agree with this date of origin and might instead suggest a younger age (10-15 Mya). Alternatively, the low level of detected mtDNA variation would agree with the traditional old-age estimate if an extremely slow rate of mtDNA evolution is postulated for this group. This slow-rate hypothesis, if true, could be explained by decreased metabolic rates slowing down the tempo of molecular evolution.

Animals↗
PubMed1994

Differential changes in intestinal permeability following burn injury.

Increased gut permeability (GP) following burn injury has been implicated in the predisposition to sepsis and multiple systems organ failure (MSOF). Since previous studies have identified only "global" alterations in GP, we examined the jejunum, ileum, and colon individually for GP using probes of two different sizes: fluorescein isothiocyanate-dextran-3 (FDEX, molecular weight 4387 d) and horseradish peroxidase (HRP, molecular weight 40,000 d). Animals were examined for GP at 1, 2, or 4 days following burn. The GP was significantly increased in all segments combined following burn injury to both the small probe (FDEX, p < 0.001) and the larger probe (HRP, p < 0.06) versus controls. The GP was significantly greater for FDEX versus HRP (p < 0.001). Jejunal permeability to FDEX and HRP increased most at 24 hours. Ileal and colonic GP to FDEX increased early also, but were higher at days 2 and 4. These results suggest that, following burn injury, there is differential GP that is size and site dependent, and that increased GP may last well beyond 24 hours postburn despite feeding.

Analysis of Variance↗
PubMed1994

The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by an increased oxidant burden and by a deficiency of glutathione, a major antioxidant, in the lung epithelial lining fluid (ELF). Therefore, a rational therapeutic approach is to reverse the imbalance between oxidants and antioxidants in the lung by enhancing the antioxidant screen. With this background, the aim of our study was to evaluate oral N-acetylcysteine (NAC) as a strategy to augment lung glutathione levels in patients with IPF. Concentrations of total glutathione in bronchoalveolar lavage fluid (BALF) were quantified spectrophotometrically, before and following oral therapy with 3 x 600 mg NAC per day for 5 days, in 17 nonsmoking patients with biopsy-proven IPF. The volume of ELF recovered by BAL was determined using the urea method. Pretherapy, total glutathione levels in ELF in IPF patients were significantly less than normal (187 +/- 36 vs 368 +/- 60 microM), in contrast to levels in BALF (0.99 +/- 0.12 vs 1.18 +/- 0.19 microM). Following therapy with oral NAC, glutathione levels in BALF were 1.54 +/- 0.24 microM (a significant increase compared to pretherapy), whereas the increase in ELF levels (319 +/- 92 microM) did not reach significance. The therapy was well-tolerated, and all routine clinical and bronchoscopic parameters remained unchanged. It is thus feasible and safe to augment deficient lung glutathione levels in patients with IPF; thereby, potentially augmenting pulmonary antioxidant protection.

Acetylcysteine↗
PubMed1994

Mutations in p53 produce a common conformational effect that can be detected with a panel of monoclonal antibodies directed toward the central part of the p53 protein.

Human p53 displays two immunodominant regions localized in the amino and carboxy termini of the protein. Using a truncated p53 (residues 66 to 361), we selected eight new monoclonal antibodies directed to the central part of the protein. We identified the epitopes recognized by seven out of eight antibodies with a set of overlapping peptides. One of these antibodies had an epitope similar to PAb240, whereas the others recognized novel and diverse antigenic determinants. Using a series of 19 p53 mutants, we show that the behavior of several of the new monoclonal antibodies is similar to that of PAb240 despite their various epitope localizations. This suggests that different mutations in the p53 protein induce an overall conformational change that can be detected by various monoclonal antibodies directed toward the central part of the protein.

Amino Acid Sequence↗