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Biomedical subjects

E Richter

Publications and source records attributed to E Richter.

At least 19 recordsLinked to original sources
PubMed1995

Characterisation of cell movement by impedance measurement on fibroblasts grown on perforated Si-membranes.

Mouse fibroblasts grown on perforated Si-membranes (pore diameter approximately 10 microns have been studied to clarify cell locomotive ability. The cell motility was microscopically monitored by a time-lapse video system and, simultaneously, the impedance of the growing cells was measured every 5 s. The correlations between observed cell activities and measured impedance events are discussed and classified. The method is sensitive and allows discrimination between signals arising from translocation of single cells and those arising from filopodia activities. Both cell and filopodia motion could be detected. Designs of microdevices fabricated in semiconductor technology are presented.

3T3 Cells↗
PubMed1995

Synthesis, pharmacologic activity, and structure-activity relationships of a series of propafenone-related modulators of multidrug resistance.

A series of [(o-acylaryl)oxy]propanolamines have been prepared and evaluated for multidrug resistance-reverting activity in a human tumor cell model. Structure-activity relationship studies indicate that the phenylpropiophenone moiety as well as the substitution pattern at the nitrogen atom is crucial for activity of the compounds. Incorporation of the ether oxygen into a benzofuran substructure, which renders the compound an arylethanolamine, decreased biologic activity. Highest activity could be observed with the arylpiparazines 4f-h, which not only completely restored daunomycin sensitivity but also showed moderate activity in restoring etoposide toxicity.

Daunorubicin↗
PubMed1995

An improved method for the species-specific assessment of mycobacteria in routinely formalin-fixed and paraffin-embedded tissues.

A polymerase chain reaction (PCR) assay for the rapid and species-specific diagnosis of mycobacterial infections in paraffin-embedded clinical specimens was developed using oligonucleotide primers to amplify a fragment of the DNA coding for the ribosomal 16S RNA of mycobacteria. The oligonucleotide primers amplified DNA from all 14 species of mycobacteria tested. By means of a reamplification protocol, as few as one to two mycobacteria could be detected in the presence of human DNA. The method of DNA isolation and amplification was applied on sections of routinely formalin-fixed and paraffin-embedded tissues. PCR for the beta-actin gene served as a control for successful DNA isolation. Mycobacterial DNA could be detected in cases of mycobacterial infections. The mycobacterial species was determined by additional sequencing of the PCR fragment. This PCR method may be a powerful tool for the diagnosis of mycobacterial infections from histopathological material and for the assessment of those mycobacteria that cannot readily be cultured, such as Mycobacterium leprae.

Base Sequence↗
PubMed1995

Intestinal metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats: Sex difference, inducibility and inhibition by phenethylisothiocyanate.

The intestinal metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated in male and female Sprague-Dawley (SD) rats and male F344 rats, using isolated perfused intestinal segments. [1(-14)C]-NNK at 1 microM was metabolized by alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction. Jejunal segments from control female rats metabolized 26.2% of the NNK during transepithelial transfer to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, 12.2%), 4-(methylnitrosamino)-1-3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide, 7.7%), 4-oxo-4-(3-pyridyl)-butanol (KAlc, 2.7%), 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide, 1.8%), 4-oxo-4-(3-pyridyl)butyric acid (KA, 1.1%) and 4-hydroxy-4-(3-pyridyl)butyric acid (HA, 0.7%). Ileal segments metabolized 20.8% of the NNK during absorption, with no difference in metabolite distribution as compared to jejunal segments. In control male SD and F344 rats, jejunal presystemic metabolism was 2.3-fold higher (56.4% and 60.8% respectively), mainly because of a 4-fold increase in NNAL formation (44.1% and 48.5%)> total NNK metabolism was also induced in female rats by starvation (84.4% metabolites), acetone (89.3%), phenobarbital PB, 75.3%) and Clophen A50 (61%). PB and Clophen A50 induced N-oxidation to 38.9% (4 x) and 27.8% (3 x), and to a lesser extent NNAL formation and alpha-hydroxylation (2 x), Starvation mainly increased N-oxidation with a time-dependent increase from 1 day to 3 days of starvation (4 x and 8 x versus controls), whereas alpha-hydroxylation and NNAL formation was elevated only after 1 day starvation. Acetone pretreatment (3 days) stimulated all three pathways (NNAL 2 x, N-oxidation 4 x, alpha-hydroxylation 4 x). In male F344 rats, starvation and acetone induced N-oxidation (5 x and 7 x) and alpha-hydroxylation (3 x and 5 x), and decreased NNAL formation by 40%, probably due to substrate competition or further metabolism of NNAL. In acetone-induced female SD rats, NNK metabolism was inhibited by in vivo pretreatment with phenethylisothiocyanate (PEITC) or in vitro addition of 1% ethanol to the perfusate. Both inhibition experiments reduced total metabolism by 20%; N-oxidation and alpha-dhyroxylation were reduced to values found in control rats, whereas NNAL formation increased from 31% to 51%.Inhibition of NNK metabolism by PEITC im male F344 rats was less pronounced compared to female SD rats; again a decrease in alpha-hydroxylation (6.7% to 3.3%) and N-oxidation (73.6% to 35.3) was accompanied by increased NNAL formation (9.8% to 41.0%).(ABSTRACT TRUNCATED AT 400 WORDS)

Acetone↗
PubMed1995

Localization of thioredoxin in the rat brain and functional implications.

The immunoreactivity for thioredoxin, which catalyzes protein disulfide reductions, has previously been shown to exist in nerve cells and their axons. Here we demonstrate the localization of thioredoxin mRNA as revealed by in situ hybridization in the rat brain. The gene is expressed in nerve cells of a variety of brain regions, for example, the cerebral cortex, the piriform cortex, the medial preoptic area, the CA3/CA4 region of the hippocampal formation, the dentate gyrus, the paraventricular nucleus of the hypothalamus, the arcuate nucleus, the substantia nigra pars compacta, the locus coeruleus, the ependyma of the 4th ventricle, and the epithelial cells of the choroid plexus. This distribution implicates an important function in nerve cell metabolism, especially in regions with high energy demands and indicates a role of the choroid plexus in nerve cell protection from environmental influences. It was found that after mechanical injury induced by partial unilateral hemitransection the thioredoxin mRNA expression is upregulated in the lesioned area and spreads to the cortical hemispheres at the lesioned level. This induction suggests a function of thioredoxin in the regeneration machinery of the brain following mechanical injury and oxidative stress.

Animals↗
PubMed1995

CD26 expression in leprosy and other granulomatous diseases correlates with the production of interferon-gamma.

BACKGROUND: Leprosy represents a spectrum of clinical manifestations that reflect the immune response to antigens of Mycobacterium leprae. The tuberculoid form of leprosy, which is characterized by an organized development of granulomas, has recently been correlated with a Th1-like immune response. The lepromatous form of leprosy, with a characteristic lack of cellular immunity, has been correlated with a Th2-like immune response to mycobacterial antigens. Dipeptidylpeptidase IV (CD26) is an ectopeptidase that is expressed in various tissues; in the hemopoietic system, it is predominantly expressed by T cells. EXPERIMENTAL DESIGN: We stained frozen sections of skin biopsies obtained from patients with different forms of leprosy, sarcoidosis, and Piringer's lymphadenitis. Sections were stained for interferon-gamma (IFN-gamma) and CD26 with the alkaline phosphatase anti-alkaline phosphatase technique and in two-color stainings by immunofluorescence. RESULTS: We found strong signals for IFN-gamma and for CD26 in all investigated cases of tuberculoid leprosy. In contrast, in all biopsies taken from patients with lepromatous leprosy, we found no or very weak signals for these antigens. By immunofluorescence double-labeling, we could show that IFN-gamma and CD26 were expressed by the identical cell population. We confirmed this correlation of CD26 expression and IFN-gamma production in other granulomatous inflammatory reactions such as sarcoidosis and Piringer's lymphadenitis. CONCLUSIONS: From our results, we conclude that a high expression of CD26 may be suggestive of Th1-like immune reactions.

Dipeptidyl Peptidase 4↗
PubMed1994

Biomonitoring of hemoglobin adducts: aromatic amines and tobacco-specific nitrosamines.

A new analytical procedure has been developed for the simultaneous determination of human hemoglobin adducts from aromatic amines and tobacco-specific nitrosamines. These tobacco-related hemoglobin adducts were determined in nonsmokers, smokers, and users of nasal snuff. Adducts from aminobiphenyl compounds are good biomarkers of exposure to tobacco smoke; they are not elevated in users of nasal snuff. However, a significant contribution of environmental exposure to aromatic amines and/or the corresponding nitroaromatics makes it difficult to evaluate passive exposure to tobacco smoke. The best biomarkers for exposure to tobacco smoke should in theory be adducts arising from tobacco-specific nitrosamines. The common adduct from N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone releases 4-hydroxy-1-(3-pyridyl)-1-butanone from hemoglobin upon mild alkaline hydrolysis and only marginal differences are found in the adduct level in smokers and nonsmokers. The reason for this observation is not yet understood and is currently under investigation. However, the adduct formed by tobacco-specific nitrosamines is well suited for the detection of oral and nasal tobacco use. Only by simultaneous determination of both adducts formed by aromatic amines and tobacco-specific nitrosamines is it possible to differentiate between nonsmokers, smokers, and nasal snuff users.

Aminobiphenyl Compounds↗
PubMed1994

Metabolism of a glucuronide conjugate of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats.

Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), [4-(methylnitrosamino)-1-(3-pyridyl)butl-yl]-beta-O-d-glucosidu ronic acid (NNAL-Glu) is another important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which has been detected in the urine of tobacco users and non-smokers heavily exposed to sidestream cigarette smoke. In order to evaluate the toxicological significance of NNAL-Glu formation and excretion, the metabolism of [5-3H]-NNAL-Glu was studied in rats. Five male F344 rats were administered 3.7 mg/kg [5-3H]-NNAL-Glu by i.v. injection and the metabolites in urine analysed by HPLC. More than 90% of the radioactivity was excreted in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2 +/- 3.1% of the total radioactivity; the remaining part of the dose appears to be deconjugated resulting in the urinary excretion of NNAL (3.6 +/- 1.7%) and its alpha-hydroxylation (11.5 +/- 2.2%) and N-oxidation (3.6 +/- 1.6%) products. The presence of alpha-hydroxylation products of NNAL-Glu in urine suggests that this NNK metabolite may be activated in vivo to carcinogenic intermediates.

Animals↗
PubMed1994

Detection of Mycobacterium leprae by three-primer PCR.

Recently, polymerase chain reaction has been introduced for the species-specific assessment of Mycobacterium leprae (1). To avoid Southern blotting techniques using radioactively labelled oligonucleotide probes, the aim of this study was to establish a three primer-based single-step PCR technique. Using primers designed for this purpose we amplified a part of the gene encoding for the 16S ribosomal RNA of slowly growing mycobacteria. Due to the species-specific antisense primer a second, smaller fragment specific for M. leprae was amplified. Our results show that the employment of a second antisense primer in the PCR may be a substitution for Southern blot hybridization.

Base Sequence↗
PubMed1994

Mycobacterium leprae DNA content, cellular and cytokine patterns in skin lesions of leprosy patients undergoing multidrug therapy (MDT).

Skin biopsies from untreated and MDT-treated patients were examined for infiltrating cells and cells producing the cytokines TNF-alpha, IFN-gamma, and IL-1 beta using immunohistochemistry. Biopsy specimens from untreated tuberculoid leprosy patients were characterized by the presence of cells producing TNF-alpha, IFN-gamma, and IL-1 beta and of subepidermal Langerhans cells. These cells were rarely found or completely absent in biopsies of untreated lepromatous leprosy patients, but tended to increase under MDT. In a short-term therapy trial for three months with brodimoprim, dapsone, and rifampicin, 12 patients were monitored by follow-up biopsies. Semiquantitative PCR for mycobacterial DNA revealed two groups of patients: one group in which mycobacterial DNA in follow-up biopsies remained constant and a second group in which a decrease of mycobacterial DNA during therapy was noted. Immunophenotyping in these follow-up biopsies revealed that in the latter group IFN-gamma-positive cells and Langerhans cells were present and gamma delta T cell receptor-positive cells tended to decrease during therapy. In contrast, in patients whose mycobacterial DNA did not change during therapy, these phenotypical manifestations were not observed. We therefore, conclude that assessment of mycobacterial DNA in combination with phenotyping of infiltrating cells and determination of cytokine patterns may be useful tools in establishing criteria for the effectiveness and duration of MDT in patients with leprosy.

Anti-Bacterial Agents↗
PubMed1994

[Long-term results of stapes surgery with the Schuknecht wire-teflon prosthesis].

Early and late postoperative findings in 78 cases of stapedial surgery with 0.6 mm Schuknecht Teflon Wire Pistons only, performed from 1983 to 1987, were analysed to evaluate the supposition of an inverse relationship of the size of the footplate fenestration and functional long-term results. In respect of the size of fenestration our surgical strategy resulted in 3 different situations: stapedotomy (26)--partial platinectomy (34)--stapedectomy (19). Mean air conduction thresholds for frequencies 0.5-4 kHz were evaluated preoperatively, one month and > 5 years postoperatively. The results were postoperatively significantly better in all 3 groups without significant intergroup differences. > 5 years postoperatively the best results were seen in the partial platinectomy group better than after stapedotomy and significantly better than in the stapedectomy group. With regard to overclosure, closure of the air bone gap and deterioration of bone conduction thresholds at 4 kHz for the same groups, no significant differences were noticed. In conclusion, the best long-term results were obtained after partial platinectomy, i.e. there was no inverse relation of the size of the footplate perforation and the best results. The perforation should be large enough to prevent tilting of the piston at the edge. Removal of larger parts should be omitted. In case of early mobilisation and stapedectomy good long-term results can still be expected.

Auditory Threshold↗
PubMed1994

Nicotine inhibits the metabolic activation of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats.

The effect of nicotine on the metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was studied in rats. [1-14C]NNK was s.c. injected at a dose of 0.08 mumol/kg. Co-administration of a 500-fold higher dose of nicotine (40 mumol/kg) did not reduce the overall urinary excretion of radioactivity. However, the metabolic pattern in 24 h urine was significantly changed. Metabolites resulting from NNK activation by alpha-hydroxylation were significantly (P < 0.001) reduced to 72% of the control. Detoxification to N-oxides and the glucuronide of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol increased to 155% (P < 0.01) and 188% (P < 0.01) of the control respectively. These results suggest that nicotine, which occurs in concentrations up to 30,000-fold higher than NNK in mainstream smoke of cigarettes may have a protective effect against metabolic activation of NNK.

Animals↗
PubMed1994

Visualization of neonatal anatomy and pathology with a new computerized three-dimensional model as a basis for teaching, diagnosis and therapy.

A new computerized three-dimensional (3D) volume model derived from a post-mortem MRI series of the chest and abdomen of a human newborn allows interactive dissection by removing, adding organs or cutting in unlimited directions. The advanced technique of real volume visualization instead of using contours allows one to study the normal and pathological anatomy of the neonate. Anatomical details of the pleural, pericardial and peritoneal cavities and of abdominal veins are demonstrated. Compared to conventional methods, the advantages of this model for teaching and as a basis for diagnostic imaging and therapeutic procedures are evident.

Abdomen↗
PubMed1994

Asthma in Gaza refugee camp children and its relationship with house dust mites.

Three hundred asthmatic children aged 3 to 15 years, and 100 age-sex-neighborhood matched controls, were studied for environmental risk factors for asthma during 1986 to 1987. In 98% of the asthmatic patients, exposure to house dust aggravated the symptoms. In 97% of the cases, the symptoms were more severe at home; in more than 50%, the symptoms persisted throughout the year. Significantly more cigarettes were smoked in the homes of the allergic children than in the control homes. House dust samples from homes of 20 asthmatic and 20 nonasthmatic children were examined for the presence of house dust mites. Twelve species of mites were identified, of which Dermatophagoides pteronyssinus, the most prevalent (97%), was found in all samples examined. The average number of mites per gram dust was 447 in homes of children with asthma, and 399 in homes of controls. Although dust and mites seem to be the most important factors causing allergies in Gaza and most of the children are exposed to large numbers of mites in their homes, it appears that those who are genetically predisposed and who are exposed to environmental tobacco smoke are at greater risk for allergic symptoms.

Adolescent↗