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Biomedical subjects

A Richter

Publications and source records attributed to A Richter.

At least 253 records · Page 14Linked to original sources
PubMed1995

[Adrenal incidentaloma].

Asymptomatic adrenal tumors are discovered more and more frequently with improving quality of diagnostic imaging. Treatment of these tumors, described as incidentalomas is controversial and depends on the one hand on the size of the tumor and on the other hand on morphological appearance in diagnostic imaging. In the literature a tumor size over 3 cm is in general regarded as an indication for operation, based on findings of Copeland et al. where the size of the tumor was correlated with malignancy. In the Department of Surgery in Mannheim 28 operations on adrenal incidentalomas have been performed between 1973-1993. In three patients a carcinoma was found. Four of the removed tumors each of them benign had a diameter smaller than three centimeters. An operation seems to be justified under certain conditions, even in small tumors, because potentially malignant tumors can undergo early and radical surgery. A general recommendation for treatment of the above mentioned tumors, depending only on size and morphology in diagnostic imaging, seems to be difficult. The decision for surgical therapy needs to be evaluated individually for every patient.

Adrenal Gland Neoplasms↗
PubMed1995

[Long-term survival after surgical therapy of T4 colorectal carcinomas].

Between 1972 and 1990, 456 patients with locally advanced colorectal carcinomas (tumor stage T4) were operated. In 187 cases the operation was extended by multivisceral resection and in 269 patients a conventional resection was performed. The rate of curative R0-resections was 74.9% for the extended resection group compared to 66.2% for the conventional group. The postoperative mortality after extended resection was 4.9% (2.9% conventional resection). Analyses of long-term results showed a 5-year survival for all R0-resected cases of 52.1% +/- 4.1. Further evaluation of additional lymph-node involvement in T4 colorectal tumors revealed significant differences in 5-year survival: 64.8% T4N0; 27.9% T4N1,2; 9.2% T4N3 for conventional R0-resection and 59.9% T4N0; 23.2% T4N1,2; 6.6% T4N3 for extended R0-resection. After curative resection (R0) the presence or absence of intraoperative tumor-cell dissemination could be identified as a significant prognostic factor. In all cases of T4 colorectal carcinomas-especially for N1-3-an adjuvant treatment after conventional or extended R0-resection is recommended.

Adult↗
PubMed1995

[Gynecologic laparoscopy in sheep. 2. Applications].

The gynaecological laparoscopy is basical for the correct diagnosis of the ovaries and the uterus in sheep. Physiological (follicles, corpora lutea) and pathological findings (follicle cysts) are described and illustrated. Further, application techniques of the laparoscopic intrauterine insemination as well as of the embryo recovery and embryo transfer in embryo transfer programs are explained.

Animals↗
PubMed1995

[Gynecological laparoscopy in sheep. 1. Foundations].

Laparoscopy is a gentle and safe method for diagnosis and manipulation of the genital tract in female sheep. After a short history outline the equipment and the fundamental principles of the laparoscopy in sheep are described. Possible laparoscopic incidents and their treatment are explained.

Animals↗
PubMed1995

[Diagnostic and therapeutic problems of acute lower gastrointestinal hemorrhage].

In a four year period (1990-93) 75 patients were treated in our hospital for acute lower gastrointestinal bleeding. In the course of diagnostic procedures an upper gastrointestinal bleeding was excluded routinely and further 126 endoscopic measures were performed. All patients underwent rectoscopy and additional partial or total coloscopy. In addition to that, 16 scintigrams and 7 angiograms were taken. The validity of the endoscopic measures was 0.73, scintigraphy and angiography were less valid with 0.53 and 0.34. Therefore endoscopic diagnostic procedures are of more value. 32 of these 75 patients underwent operative treatment. Recurrent bleeding after operative treatment was seen in 6.25%. Overall mortality was 5.33%. Because prognosis of a recurrent bleeding after operative treatment is poor, primary subtotal colectomy is indicated when the source of bleeding can not be localized.

Aged↗
PubMed1994

(+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters.

The effects of the novel high affinity cannabinoid receptor agonist (+)-WIN 55,212-2 ((R)-4,5-dihydro-2-methyl-4(4-morphoinylmethyl)-1-(1-naphthalen ylcarbonyl)-6H-pyrrolo[3,2,1-ij]quinolin-6-one) on severity of dystonia were investigated in mutant Syrian hamsters with primary generalized dystonia. Following injections of (+)-WIN 55,212-2 (1.0-5.0 mg/kg i.p.) a dose-dependent reduction of the severity of dystonia was observed. At antidystonic doses (2.5 and 5.0 mg/kg i.p.) (+)-WIN 55,212-2 caused a reduction of spontaneous motor activity and catalepsy. 1 mg/kg of (+)-WIN 55,212-2 exhibited neither antidystonic effects nor any side effects. However, the coadministration of 1.0 mg/kg (+)-WIN 55,212-2 with an ineffective dose of diazepam (0.1 mg/kg i.p.) exerted antidystonic effects in the absence of severe side effects. Although psychotropic effects of cannabinoids, such as (+)-WIN 55,212-2, limit the therapeutical utility of cannabinoids, the present data indicate that cannabinoids exert antidystonic effects and that low doses of cannabinoids may increase antidystonic efficacy of benzodiazepines.

Analgesics↗
PubMed1994

The novel antiepileptic drug, lamotrigine, exerts prodystonic effects in a mutant hamster model of generalized dystonia.

Recent findings of antidystonic effects of NMDA and non-NMDA receptor antagonists in an inbred line of Syrian hamsters with primary generalized dystonia prompted us to investigate the effects of lamotrigine, an inhibitor of veratrine-induced glutamate release, on the severity of dystonia in mutant hamsters. In mutant dystonic hamsters the dystonic attacks which can be induced by mild environmental stimuli or handling are age-dependent with maximum severity between days 30 and 40 of life (maximum period). Thereafter the severity of dystonia slowly declines (post-maximum period) until the susceptibility to induction of dystonia disappears completely at an age of about 70 days. Lamotrigine (5.0, 10.0 or 30.0 mg/kg i.p.) dose dependently decreased the latency to onset of dystonic attacks. Furthermore, at a dose of 30 mg/kg the dystonic attacks were aggravated when lamotrigine was administered during the max and post-max period. Even in mutant hamsters older than 70 days, i.e. after spontaneous remission of dystonia, and in an inbred line of non-dystonic Syrian hamsters with genetic origin similar to the mutant hamsters, lamotrigine (10.0 or 30.0 mg/kg i.p. and 30.0 mg/kg p.o.) provoked dystonic disturbances. In a genetically different outbred line of Syrian hamsters, lamotrigine did not cause dystonic movements. The unexpected finding that lamotrigine exerts prodystonic effects in genetically susceptible hamsters may be due to the lack of selectivity of lamotrigine to block glutamate release. Tentatively, simultaneous inhibition of GABA (gamma-aminobutyric acid) release might be critically involved in the prodystonic activity of lamotrigine.

Administration, Oral↗
PubMed1994

Marked regional disturbances in brain metabolism of monoaminergic neurotransmitters in the genetically dystonic hamster.

The genetically dystonic hamster is an animal model of idiopathic (torsion) dystonia that displays sustained abnormal movements and postures either spontaneously or in response to mild environmental stimuli. Since dystonic attacks occur in the absence of any lesion which can be defined by standard histopathological techniques in the central nervous system, the presumption is that dystonia in mutant hamsters is due to some biochemical disturbance activity in brain regions involved in motor functions. In the present study we determined the monoamine neurotransmitters dopamine, noradrenaline, adrenaline and serotonin (5-HT) as well as the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) in 14 brain regions of male and female dystonic hamsters and age-matched non-dystonic controls. All determinations were done at age of maximum susceptibility for induction of dystonic attacks. Since both genders of dystonic hamsters exhibit the same characteristic age-dependent time-course of dystonia, it was assumed that only those biochemical alterations are critically involved in dystonia that occur in both female and male animals. The neurochemical data show that except for a significant decrease of dopamine and HVA in the olfactory bulb, no consistent changes in dopamine metabolism are present across brain regions, including the basal ganglia, of dystonic hamsters. In contrast, marked increases in noradrenaline and 5-HT or 5-HIAA were found in several brain areas of both genders, indicating an enhanced activity of central noradrenergic and serotonergic nuclei in the brainstem. The present results suggest the involvement of noradrenergic and serotonergic neural systems in the pathophysiology of dystonia. Based on these data and recent theoretical suggestions from clinical findings, drugs which reduce noradrenergic and serotonergic neurotransmission may be a useful therapeutic approach to dystonia.

Animals↗
PubMed1994

Purification of two isoforms of hnRNP-U and characterization of their nucleic acid binding activity.

The scaffold attachment factor A (SAF-A; Romig et al., 1992), a human nuclear protein which specifically binds vertebrate SAR (scaffold attached region) DNA, is identical with hnRNP-U (Kiledjian & Dreyfuss, 1992). In this paper, we report on the purification of two forms of this protein that can be chromatographically separated. We show that the purified proteins represent two isoforms, form 1 and form 2 hnRNP-U, which differ in their primary structure. Both isoforms bind to double- and single-stranded DNA and RNA. In addition, they form higher ordered nucleic acid/protein complexes and specifically bind and aggregate the human SAR element MII at physiological ionic strengths. Electron microscopic analysis shows that the isoforms differ from each other, as form 1 hnRNP-U aggregates into long unbranched filamentous protein/DNA complexes whereas form 2 hnRNP-U aggregates as spheres with an average diameter of 35 nm.

Amino Acid Sequence↗
PubMed1994

Structural studies on bioactive compounds. 23. Synthesis of polyhydroxylated 2-phenylbenzothiazoles and a comparison of their cytotoxicities and pharmacological properties with genistein and quercetin.

A series of polyhydroxylated 2-phenylbenzothiazoles 3 has been prepared by demethylation of the precursor methoxylated 2-phenylbenzothiazoles 9. The key step in the construction of the benzothiazole nucleus involves a Jacobson cyclization of methoxylated thiobenzanilides 8. The target compounds inhibit WiDr human colon tumor cells and MCF-7 human mammary tumor cells in vitro with IC50 values in the low micromolar range, but the activity against MCF-7 cells is not related to estrogen receptor-binding affinity. None of the compounds showed selective cytotoxicity against Abelson virus-transformed ANN-1 cells encoded with the pp120gag-abl tyrosine kinase compared with the parental 3T3 line. Compounds were only marginally inhibitory to the EGF receptor-associated protein tyrosine kinase from a membrane preparation of A431 cells. The most active compound was 4,6-dihydroxy-2-(4-hydroxyphenyl)benzothiazole (3b) which has the same overall hydroxyl substitution pattern as genistein (1a). The compounds were weakly cytotoxic for an EGF receptor, overexpressing cell line HN5, but when tested for differential toxicity against the EGF receptor tyrosine kinase or the PDGF receptor tyrosine kinase in a standard mitogenesis assay utilizing human fibroblasts, no discrimination was observed. In this assay, the compounds inhibited DNA synthesis when added to cells during S phase. This suggests that inhibition could not be interpreted in terms of tyrosine kinase inactivation but more likely as a relatively broad specificity for the ATP-binding domain of other kinases such as thymidine kinase.

3T3 Cells↗
PubMed1994

Conserved regulatory elements in the type I DNA topoisomerase gene promoters of mouse and man.

The gene for mammalian type I DNA topoisomerase is constitutively expressed, but also regulated by a number of external stimuli. We compared the nucleotide sequences of the human and the mouse topoisomerase I gene promoters because promoter elements, essential for basic as well as regulated gene expression, should be conserved during evolution. We found that proximal upstream sequences are highly conserved and include potential binding sites for ubiquitous transcription factors, a regulatory CRE site as well as two novel promoter elements that have been shown to be important for the expression of the human gene. The more distal parts of the upstream sequences are less well conserved but include two regions that are almost identical in the human and the mouse gene. One of these regions contains a binding site for a basic-helix-loop-helix/leucine-zipper protein, and the other contains an AT-rich element with the potential for DNA bending.

Animals↗
PubMed1994

Nucleic-acid-binding properties of hnRNP-U/SAF-A, a nuclear-matrix protein which binds DNA and RNA in vivo and in vitro.

We show that SAF-A, a nuclear protein which specifically binds vertebrate scaffold-attachment-region (SAR) elements with high affinity is identical with hnRNP-U, assumed to be involved in packaging of hnRNA in ribonucleoprotein particles. Ultraviolet cross-linking experiments show that the protein, referred to as hnRNP-U/SAF-A, is bound to chromosomal DNA in vivo. In vitro, the isolated protein binds to double-stranded and single-stranded DNA and forms higher ordered nucleic-acid-protein complexes. Filter-binding experiments performed with different types of natural and synthetic nucleic acids as substrates show that the protein binds DNA and RNA with different affinities and most likely at different binding sites. We conclude that hnRNP-U/SAF-A thus may have functions in the organisation of chromosomal DNA in addition to its suggested role in hnRNA metabolism.

Amino Acid Sequence↗
PubMed1994

The novel selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 aggravates dystonic movements in a mutant hamster model.

Several clinical and experimental findings suggest that abnormal serotonin (5-HT) function may be involved in movement disorders such as dystonia, and it was proposed that selective 5-HT1A receptor antagonists may be of benefit in treating such disorders. In the present study, the novel, highly selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 (N-tert-butyl-3(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylprop ionamide) was tested in an inbred line of Syrian hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. In order to demonstrate that WAY-100135 acts as a 5-HT1A receptor antagonist in the hamster, the drug was shown to antagonize the behavioural syndrome induced by 8-hydroxy-2-(di-n-propylamino)tetralin. When administered at 5-HT1A receptor antagonistic doses in dystonic hamsters, (+)-WAY-100135 dramatically aggravated the dystonic attacks. The data thus suggest that, in contrast to previous theoretical proposals, 5-HT1A receptor antagonists provide no novel therapeutic approach to involuntary movement disorders such as dystonia.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Characterisation of two intronic nuclear-matrix-attachment regions in the human DNA topoisomerase I gene.

We identify two high-affinity matrix-attachment regions (MAR elements) located in two introns of the human DNA topoisomerase I gene (TOP1). These intronic MAR elements, designated MI and MII, are specifically bound by the nuclear matrix and partition with scaffolds in vitro. One of these MAR elements, MII, is part of a genomic region which is hypersensitive for endogenous nucleases. We have sequenced both DNA elements and have characterized their mode of binding to the nuclear matrix. Experiments with the minor-groove-binding ligands distamycin and chromomycin indicate that the A+T-rich regions, most likely homopolymeric A tracts, are responsible for binding of these DNA elements to the nuclear matrix. MII contains an alu-like element and a segment of curved DNA. Analysis of subfragments of MII show that the curved DNA region itself shows only weak nuclear-matrix binding, and that the high-affinity binding sites are located on subfragments on the 5' side of the curved DNA. In addition, we found that the alu-like sequence does not contribute significantly to the binding of MII and of subfragments of MII to nuclear-matrix proteins. Comparing the distribution of repetitive sequences in the cloned parts of human DNA topoisomerase I gene with the location of high-affinity matrix-binding sites we find no evidence that repetitive DNA may be located close to MAR elements as has been previously suggested.

Binding Sites↗
PubMed1994

hnRNP-U/SAF-A is encoded by two differentially polyadenylated mRNAs in human cells.

Scaffold attachment factor A (SAF-A; Romig et al. (1992) EMBO J. 11, 3431-3440) is a human nuclear protein with high affinity for SAR DNA (scaffold attached region; Laemmli et al. (1992) Curr. Opin. Cell. Biol. 2, 275-285). We isolated and sequenced two classes of cDNA clones coding for SAF-A and found that their coding sequences are identical with the coding sequence of hnRNP-U (Kiledjian and Dreyfuss (1992) EMBO J. 11, 2655-2664). The two classes of cDNA clones differ, however, in the length of their 3' untranslated region and result from the use of two different polyadenylation signals. This is consistent with Northern blotting experiments which show that two mRNAs with a length of 3.9 kb and 3.1 kb, respectively, exist in human cells. Using selective cDNA fragments as probes we show that the shorter mRNA lacks 800 nucleotides of the untranslated 3' end.

Amino Acid Sequence↗
PubMed1994

U-type exchange in a paracentric inversion as a possible mechanism of origin of an inverted tandem duplication of chromosome 8.

A mentally retarded male with dysmorphic features was found to have a de novo 46,XY,inv dup(8) (p.23.1-->12). Confirmation of the segments duplicated in the rearrangement was achieved by biochemical analysis of glutathione reductase, which maps to 8p21.1, and DNA studies using the chromosome specific probe y-19-1D (D85131), which maps to 8p21. Assay of cathepsin B, which has been localised to 8p22, did not differ from controls with normal chromosomal constitution. DNA studies using the Defensin 1 gene probe, which maps to 8p23, showed a previously undetected deletion of that segment. We propose that the inverted tandem duplication/deletion arose as a single U-type exchange within an inversion loop.

Abnormalities, Multiple↗