Analysis of the deletion/insertion polymorphism of the angiotensin I-converting enzyme gene by capillary electrophoresis.
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Base Sequence↗
Biomedical subjects
M Koch
Publications and source records attributed to M Koch.
Increased startle responses in mice carrying mutations of glycine receptor subunit genes.
An exaggerated startle response caused by mutations of the alpha 1 subunit gene of the inhibitory glycine receptor (GLRA1) is the key symptom of human hyperekplexia or startle disease. The recessive mouse mutant spasmodic (spd) carries a missense mutation in the corresponding murine Glra1 gene which reduces the affinity of agonists for the mutant receptor. This mutant has been regarded as an animal model with which to investigate the molecular basis of hyperekplexia and related motor disorders. The recessive mouse mutant spastic (spa) carries an insertional mutation in the glycine receptor beta subunit gene (Glrb) that results in aberrant splicing and, consequently, in a reduced number of functionally intact receptors. The resulting phenotype is similar to that of spasmodic. This study measured the acoustic startle response of spasmodic and spastic mice under different stimulus conditions, in order to test for sensorimotor processing deficits in these animals. Both mutants show increased startle responses to acoustic stimuli of different intensities compared with wild-type animals.
Acoustic Stimulation↗
Surface Functionalization of Polyethylene Terephthalate Film and Membranes by Controlled Wet Chemistry.
Surface functionalization of polyethylene terephthalate film and track-etched microporous membranes was performed using organic synthesis at the solid-liquid interface. The hydroxyl chain ends, naturally occurring in the membranes or created by basic hydrolysis in the film, were activated by reaction with p-toluenesulfonyl chloride and then coupled to [4,5-(3)H]lysine used as a model of water-soluble bioactive molecules. The ratios of derivatization were determined by liquid scintillation counting of the radioactivity associated with the samples. The hydroxyl chain ends were further reacted with 4,4'-methylene di(phenyl isocyanate); the resulting surfaces equipped with sensitive isocyanate spacers were assayed as before using [4,5-(3)H]lysine. The ranges of derivatization were from 5 to 60 pmol of fixed amino acid per open surface unit (cm(2)). Some samples were also analyzed by X-ray photoelectron spectroscopy.
Journal Article↗
Cysteamine impairs the development of the acoustic startle response in rats: possible role of somatostatin.
Somatostatin is transiently expressed in many regions of the developing brain, among others in auditory brainstem nuclei of neonatal rats. To explore the functional significance of somatostatin during the ontogeny of acoustically elicited behavior, the acoustic startle response (ASR) was measured in developing rats after chronic application of cysteamine, which, when applied in low doses, most selectively depletes somatostatin. Cysteamine treatment drastically reduced somatostatin immunoreactivity in the cochlear nuclear complex and the caudal pontine reticular nucleus, i.e. in structures mediating the ASR. It did not affect the ASR amplitude of postnatal day (P) 13 animals, yet it resulted in a significant reduction of the ASR amplitude at P18. Our results therefore suggest that somatostatin can influence the maturation of sensorimotor information processing.
Acoustic Stimulation↗
Effects of sulglycotide on inflammation and epithelial cell turnover in active Helicobacter pylori+ chronic gastritis. A pilot study.
The effects of Sulglycotide were evaluated in a pilot study of active H. pylori+ atrophic gastritis. Ten informed patients (mean age 51 +/- 13 years) entered a double-blind study. Five received Sulglycotide 400 mg three times a day for one year, the other 5, placebo. At 0, 30, 90, 270, and 360 days of treatment, patients underwent endoscopic examinations with multiple biopsies. Morphometric studies (number of inflammatory cells and percent gland volume), morphologic studies (according to the Sydney system), and flow cytofluorimetry were performed in all cases. Compared to findings in the placebo group, patients treated with Sulglycotide showed a reduced number of inflammatory cells and an increase in gland volume 120 days after treatment. While the difference was not statistically significant, the trend was confirmed by the morphologic patterns. Flow cytofluorimetry revealed an increase in the percentage of cells in the G2 phase (full maturation) and a parallel drop in the S phase (premitotic synthesis) in the Sulglycotide group only in the first three months. These data would appear to indicate an acceleration of gastric epithelial cell maturation and a decrease in the inflammatory infiltrate under the effect of Sulglycotide.
Adult↗
Identification of N2 as a metabolite of acetylhydrazine in the rat.
In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [14C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [15N]-nitrogen and 14CO2 exhalation, after the administration of [15N2]-[14C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of 15N and 14N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB+cobalt(II) chloride (CoCl2) (n = 3 in each group). Time-dependent 15N2 exhalation differed significantly between treatment groups (p < 0.001). At 240 min, cumulative exhalation of 15N was 1.92 +/- 0.43% (mean +/- SE) of the dose in the control group, 2.53 +/- 0.23% in the PB group, and 1.00 +/- 0.15% in the PB+CoCl2 group (p < 0.05 compared to controls, p < 0.01 compared to PB). Cumulative exhalation of 14CO2 in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N2 is a metabolite of AcHz. N2 formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N2-liberating process in vivo.
Animals↗
The clinical and genetic correlates of MRI findings in myotonic dystrophy.
Amplification of an unstable CTG trinucleotide repeat sequence in a protein kinase gene on chromosome 19 has recently been recognised as the molecular basis of myotonic dystrophy (DM), a multi-system disorder with a wide spectrum of muscular and extramuscular manifestations. The CTG expansion of 40 patients was assessed by direct genotype analysis of the white blood cell DNA and correlated with MRI of the brain and muscles, and with functional clinical data. Cerebral pathology on MRI consisted of diffuse atrophy (68%), subcortical white matter lesions (65%), wide Virchow-Robin spaces (38%) and thickening of the skull (35%). Cerebral atrophy and extent of white matter disease correlated significantly with mental retardation, duration of disease and CTG fragment amplification. MRI of the muscular system showed fatty degeneration of different degrees in neighbouring muscles causing a mosaic pattern of the thigh in 38% and the calf in 44%. Muscular changes on MRI were strongly correlated with muscular impairment but less strongly with CTG expansion. Changes on MRI reflect the stage of development of tissue pathology in DM, modified by defect of the DM gene. Pathology on MRI is strongly correlated with functional deficits.
Adolescent↗
Lesions of the central gray block conditioned fear as measured with the potentiated startle paradigm.
The amplitude of the acoustic startle response (ASR) in rats is increased in the presence of a cue which has previously been paired with an electric footshock. This phenomenon is termed fear-potentiated startle and is a useful model to investigate the neural systems underlying fear and anxiety. A series of studies have shown, that the amygdaloid complex is necessary for the acquisition and the expression of conditioned fear. Further experiments have delineated an efferent amygdalofugal pathway to the primary startle circuit, at the level of the caudal pontine reticular formation, which mediates the expression of conditioned fear [10]. Yet it was unclear, whether this amygdaloreticular pathway directly transfers the effects of conditioned fear from the amygdala to the primary startle circuit or whether there exist one or more relay nuclei within this pathway or even additional parallel circuits. Based on our previous finding that the midbrain central gray (CG) is involved in the mediation of the facilitatory effects on the ASR of unconditioned aversive events, the present study tested the hypothesis that the CG is important for the potentiation of the ASR by conditioned fear. Therefore, we lesioned the CG before and after fear-conditioning and examined the effects of these lesions on fear-potentiated startle. Pre- and post-training lesions of the CG totally blocked the potentiation of the ASR amplitude by conditioned fear, which was seen in sham-lesioned rats, indicating that CG lesions affected the expression of conditioned fear. The baseline ASR amplitude was not influenced by CG lesions. We discuss possible pathways and mechanisms underlying the expression of conditioned and unconditioned fear in rats.
Acoustic Stimulation↗
Mini mental state examination: influence of sociodemographic, environmental and behavioral factors and vascular risk factors.
Age and education have been found to affect the Mini Mental State Examination (MMSE) score of elderly normals, but there have been no studies assessing the influence of environmental and behavioral factors on this test. We therefore administered the MMSE to 1437 normal elderly subjects in the setting of a stroke prevention study and correlated their results to 16 sociodemographic, environmental, and behavioral factors, and vascular risk factors. Study statistics composed of a multiple logistic regression analysis and graphical models revealed the relations between variables in greater detail. Logistic regression yielded education level, occupational status, living as a single, general life stress, physical strain, and physical inactivity to be independent predictors of the MMSE score. Age was not included in this model. Graphical models demonstrated similar results, but did not include living as a single and physical inactivity. As shown in our independence graph, general life stress is the crucial predictor and links other environmental and sociodemographic variables with the test performance of elderly normals.
Aged↗
Lesions of the amygdala do not affect the enhancement of the acoustic startle response by background noise.
The acoustic startle response (ASR) is enhanced in the presence of loud background noise. We examined whether or not this increase of response strength is mediated by the amygdala, which is known to be involved in various phenomena of enhancement of the ASR. To achieve this aim, we tested whether or not amygdaloid lesions with the excitotoxin N-methyl-D-aspartate (NMDA) would abolish the enhancement of the ASR by background noise in 13 Wistar rats. Loss of foot-shock sensitization in these rats, as well as histological evaluation, proved the successful destruction of the amygdala. However, the enhancement by background noise of the ASR, which was observed in sham-operated controls, was not affected in amygdala-lesioned rats. Therefore, we conclude that the background noise facilitation does not involve emotional components that are mediated by the amygdala. On the basis of these findings, we differentiate between the startle-enhancing effect of background noise and the amygdala-mediated effect of foot shocks on the ASR.
Acoustic Stimulation↗
Synthesis and anti-proliferative activity of 2-hydroxy-1,2-dihydroacronycine glycosides.
PURPOSE: Combination of the acronycine pharmacophore with various sugar units appeared of interest, since numerous anticancer agents possess a sugar moiety, which strongly influence both their bioavailability and their selective toxicity towards tumor cells. METHODS: A series of 2-hydroxy-1,2-dihydroacronycine glycosides were synthetized, by condensation of the racemic aglycone with appropriate glycoside donors. Their effect on the inhibition of L1210 cell proliferation were evaluated. RESULTS: Compounds 6a, 6b, 11a, 11b, and 12a, 12b, including a halogenated sugar moiety displayed activities of the same order of magnitude as acronycine itself. Compounds 7a, 7b, and 8a, 8b, bearing a 2.3.6-trideoxy-3-azido-L-lyxo- and L-arabino-hexopyranose unit respectively, were significantly more potent than acronycine in inhibiting cell proliferation. CONCLUSIONS: The activity of 2-hydroxy-1,2-dihydroacronycine glycosides seems to be related to the lipophilicity of the sugar unit.
Acronine↗
The septohippocampal system is involved in prepulse inhibition of the acoustic startle response in rats.
Prepulse inhibition (PPI) of the acoustic startle response (ASR) can be used as an operational measure for brain mechanisms that prevent disruption of ongoing stimulus processing routines by other stimuli and that thereby avoid behavioral interference. Deficient PPI has been observed in schizophrenics; therefore, much interest has been devoted to the understanding of the neural basis of PPI. This study investigated the role of the septohippocampal system in the modulation of PPI in rats. Stimulation of the medial septum by injection of the glutamate agonist kainate led to a profound disturbance of PPI and reduced the ASR amplitude. The PPI deficit induced by intraseptal kainate was attenuated by systemic or intrahippocampal administration of the acetylcholine antagonist scopolamine. Lesions of the medial septum, made by the neurotoxin AMPA, did not affect PPI. The present data indicate that activation of the septohippocampal system reduces PPI of the ASR, suggesting its role in sensorimotor gating.
Animals↗
Tenascin-Y: a protein of novel domain structure is secreted by differentiated fibroblasts of muscle connective tissue.
Tenascin-Y was identified in chicken as a novel member of the tenascin (TN) family of ECM proteins. Like TN-C, TN-R, and TN-X, TN-Y is a multidomain protein consisting of heptad repeats, epidermal growth factor-like repeats, fibronectin type III-like (FNIII) domains and a domain homologous to fibrinogen. In contrast to all other known TNs, the series of FNIII domains is interrupted by a novel domain, rich in serines (S) and prolines (P) that occur as repeated S-P-X-motifs, where X stands for any amino acid. Interestingly, the TN-Y-type FNIII domains are 70-100% identical with respect to their DNA sequence. Different TN-Y variants are created by alternative splicing of FNIII domains. Although, based on sequence comparisons TN-Y is most similar to mammalian TN-X, these molecules are not species homologues. TN-Y is predominantly expressed in embryonic and adult chicken heart and skeletal muscle and, to a lower extent, also in several non-muscular tissues. Two major transcripts of approximately 6.5 and 9.5 kb are differentially expressed during heart and skeletal muscle development and are also present in the adult. Anti-TN-Y antibodies recognize a approximately 400-kD double band and a approximately 300-kD form of TN-Y on immunoblots of chicken heart extracts. In situ hybridization and immunofluorescence analysis of aortic smooth muscle, heart, and skeletal muscle revealed that TN-Y is mainly expressed and secreted by cells within muscle-associated connective tissue. Cultured primary muscle fibroblasts released a approximately 220-kD doublet and a approximately 170-kD single TN-Y variant only when cultured in 10% horse serum but not in medium containing 10% fetal calf serum. All TN-Y variants isolated bind to heparin under physiologically relevant conditions that may indicate an important function retained in all tenascins.
Age Factors↗
Correlation of various Crohn's disease activity indexes in subgroups of patients with primarily inflammatory or fibrostenosing clinical characteristics.
Several activity indexes, including clinical variables, laboratory variables or both, have been proposed to assess the activity and severity of Crohn's disease (CD). Although activity indexes are commonly used in clinical trials, doubts exist as to whether it is correct to group together and quantify under the same numerical expression the very heterogeneous clinical manifestations of CD. The aim of our study was to try to establish a correlation between clinical and laboratory activity indexes of CD in subgroups of patients with primarily inflammatory or primarily fibrostenosing clinical characteristics. At least two activity indexes were calculated among 232 outpatient examinations in 61 CD patients. Indexes were classified as clinical, laboratory, or both. A close correlation was observed when indexes calculated on clinical variables were compared or when those that include only or prevalently laboratory parameters were compared. Conversely, the correlation between clinical and laboratory indexes tended to be poor. Taking into consideration the subgroups of patients, the correlation between clinical and laboratory indexes was high in primarily inflammatory disease but low in the primarily fibrostenosing form. The clinical activity of CD does not always reflect the quantity of inflammation measured by laboratory parameters. This is particularly true in primarily fibrostenosing disease. Different clinical patterns of CD should always be considered in the attempt to quantify with an activity index the activity and severity of disease.
Adult↗
Regulation of extracellular matrix synthesis by mechanical stress.
The extracellular matrix (ECM) provides mechanical support to tissues and is a substrate for cell adhesion and differentiation. Cells bind to ECM via specific cell surface receptors such as integrins. When engaging with ECM ligands, these receptors can activate signal transduction pathways within the cells and may act as mechanochemical transducers. Thus, interaction of cells with ECM can modulate gene expression although the exact mechanisms are not known. Among the genes that are, in part, controlled by cell-ECM interactions are those for certain ECM components themselves. Bone cells, for example, remodel their matrix and reorient bone trabeculae in response to mechanical strain. Recently, we found that fibroblasts attached to a strained collagen matrix produce more of the ECM glycoproteins tenascin and collagen XII than cells in a relaxed matrix. In vivo, these two proteins are specifically expressed in places where mechanical strain is high. We also showed that the chick tenascin gene promoter contains a novel cis-acting, "strain-responsive" element that causes enhanced transcription in cells attached to a strained collagen matrix. Similar enhancer elements might be present in the promoters of other genes induced by mechanical stress. It can be speculated that connective tissue cells sense force vectors in their ECM environment and react to altered mechanical needs by regulating the transcription of specific ECM genes; this process is a prerequisite for matrix remodeling.
Animals↗
Synthesis and cytotoxic activity of acronycine derivatives modified at the pyran ring.
Nitration of acronycine (1) and 6-demethoxyacronycine (3) afforded 2-nitroacronycine (2) and 2-nitro-6-demethoxyacronycine (4), respectively. Reduction of 2-nitroacronycine yielded, depending on the conditions, 2-nitro-1,2-dihydroacronycine (5), 2-oxo-1,2-dihydroacronycine oxime (7) or 2-amino-1,2-dihydroacronycine (6). This latter was readily converted into 2-dimethylamino-1,2-dihydroacronycine (8), 2-acetylamino-1,2-dihydro-acronycine (9) and 2-benzoylamino-1,2-dihydroacronycine (10). The cytotoxicity of these compounds was evaluated against L1210 leukemia cells. Compounds 2 and 7 were 300- and 10-fold more potent than acronycine in inhibiting L1210 cell proliferation, respectively. Compound 2 was devoid of antitumor activity against P388 leukemia and C38 colon adenocarcinoma.
Acronine↗
[The introduction of nursing documentation, supported by electronic data processing in an old age home].
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Homes for the Aged↗
Detection of the apolipoprotein B-100 arg(3500) > gl mutation in familial defective apoB-100 by temperature-gradient gel electrophoresis.
Familial defective apolipoprotein B-100 (FDB) is caused by a point mutation in exon 26 of the apolipoprotein B gene leading to a decreased binding to the LDL-receptor. Patients with FDB have hypercholesterolemia and atherosclerotic disease. Since other mutations of apoB-100 could also cause binding abnormalities we established a temperature-gradient gel electrophoresis (TGGE) method and started to screen hypercholesterolemic patients for the presence of point mutations in this region. 4 of 43 patients were positive according to TGGE and subsequent sequencing showed the familiar guanine to adenine transition in codon 3500 in all cases.
Adenine↗