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Biomedical subjects

J Neumann

Publications and source records attributed to J Neumann.

At least 145 records · Page 8Linked to original sources
PubMed1995

Interaction of beta-adrenoceptor and adenosine receptor agonists on phosphorylation. Identification of target proteins in mammalian ventricles.

The influence of the adenosine derivative (--)-N6-phenylisopropyladenosine (R-PIA, 1 micron) and 5'N-ethylcarbox-amidoadenosine (NECA, 1 micron) on beta-adrenergic stimulated (isoproterenol, 10 nM) phosphorylation of sarcolemmal (15 kDa protein), sarcoplasmic reticular (phospholamban) and myofibrillar proteins (troponin I, C-protein) was studied in isolated 32P-labeled guinea-pig ventricles. The identification of the 15 kDa protein, phospholamban, troponin I and C-protein was based on their reaction with specific antibodies. Isoproterenol increased contractile parameters (developed tension, rate of tension development, rate of relaxation) and stimulated the phosphorylation state of a 15 kDa protein (now named phospholemman), of phospholamban, troponin I and C-protein (regarded as regulatory proteins). Isoproterenol concomitantly increased myocardial cyclic AMP levels. R-PIA and NECA attenuated the effects of isoproterenol on contractile parameters as well as on the phosphorylation of the regulatory proteins without affecting cyclic AMP levels. The effects of 1 microM R-PIA and 1 microM NECA on the isoproterenol-stimulated phosphorylation of regulatory proteins were blocked by the adenosine receptor antagonist 1.3-dipropyl-8-cyclopentylxanthine (DPCPX, 1 microM). Therefore, it is concluded that adenosine derivatives acting via adenosine receptors can reduce the isoproterenol-stimulated phosphorylation state of the following regulatory proteins: phospholemman, phospholamban, troponin I and C-protein.

Adenosine↗
PubMed1995

Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation.

OBJECTIVES: To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. METHODS: Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response. RESULTS: Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy. CONCLUSIONS: Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered for a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.

Administration, Intravesical↗
PubMed1995

Allograft conjunctival transplantation for bilateral ocular surface disorders.

PURPOSE: The purpose of this study is to evaluate the efficacy of allogenic conjunctival transplantation in bilateral surface disorders and to correlate with human leukocyte antigen (HLA) typing and cross-matching. METHODS: A prospective study of allogenic conjunctival transplantation was undertaken in 12 eyes of 10 patients with bilateral surface disorders. Five eyes had Stevens-Johnson syndrome, three had Lyell syndrome, three had bilateral alkali burns, and one had a bilateral thermal burn. Human leukocyte antigen typing and cross-matching were retrospectively performed in eight patients and their respective donors. Stabilization of corneal epithelia, visual acuity, and rejection episodes were examined after the procedure. RESULTS: Eleven (91.6%) of 12 eyes had improved visual acuity, corneal transparency and surface lubrication, stabilization of corneal epithelia, and decreased corneal neovascularization and photophobia after an average follow-up of 17.2 months. Three patients (25%) had rejection episodes, with no disturbance in corneal surface in two. Two of these three patients had 100% incompatible HLA donor-recipient pairs; HLA of the third patient was not available. Patients with favorable evolution were either HLA identical or haplo-identical (50% identity) with their donors. Donor eyes did not present any epithelial problems during the follow-up period. CONCLUSIONS: Human leukocyte antigen-matched allogenic conjunctival transplantation proved to be an adequate method of treating severe bilateral surface disorders, with minimal complications.

Adolescent↗
PubMed1995

Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice.

Basic fibroblast growth factor (FGF-2) is a pleiotropic growth factor detected in many different cells and tissues. Normally synthesized at low levels, FGF-2 is elevated in various pathologies, most notably in cancer and injury repair. To investigate the effects of elevated FGF-2, the human full-length cDNA was expressed in transgenic mice under control of a phosphoglycerate kinase promoter. Overexpression of FGF-2 caused a variety of skeletal malformations including shortening and flattening of long bones and moderate macrocephaly. Comparison by Western blot of FGF-2 transgenic mice to nontransgenic littermates showed expression of human FGF-2 protein in all major organs and tissues examined including brain, heart, lung, liver, kidney, spleen, and skeletal muscle; however, different molar ratios of FGF-2 protein isoforms were observed between different organs and tissues. Some tissues preferentially synthesize larger isoforms of FGF-2 while other tissues produce predominantly smaller 18-kDa FGF-2. Translation of the high molecular weight isoforms initiates from unconventional CUG codons and translation of the 18-kDa isoform initiates from an AUG codon in the FGF-2 mRNA. Thus the Western blot data from the FGF-2 transgenic mice suggest that tissue-specific expression of FGF-2 isoforms is regulated translationally.

Animals↗
PubMed1995

Comparison of the stereoselective effects of a thiadiazinone derivative on contractile parameters and protein phosphorylation in the mammalian ventricle.

In papillary muscles from reserpinized guinea pigs, EMD 57033, the most potent Ca(2+)-sensitizer known, effectively increased force of contraction (FOC) and concomitantly increased duration of contraction. In isolated 32P-labeled guinea pig ventricular cardiomyocytes, EMD 57033 increased the phosphorylation state of phospholamban as well as the inhibitory subunit of troponin, which are usually linked to reductions in contraction time. Therefore, EMD 57033 dissociates phospholamban-phosphorylation and effects on contractile parameters, probably owing to its strong Ca(2+)-sensitizing properties.

Adenosine Triphosphatases↗
PubMed1995

On the cardiac contractile, biochemical and electrophysiological effects of cantharidin, a phosphatase inhibitor.

Cantharidin concentration dependently increased the force of contraction in isolated guinea pig papillary muscles (1-100 microM). The positive inotropic effect is accompanied by a reduction in time to peak tension and relaxation time. Cantharidin did not exert a positive chronotropic effect in spontaneously beating right atria. L-type calcium channel currents of guinea pig cardiomyocytes were moderately increased by cantharidin (by about 20%), both at the whole-cell level (2 mM Ca2+) and at the single channel level (70 mM Ba2+). There was a correspondingly small increment of single channel availability. Additionally, a larger proportion of single-channel sweeps displayed high open probability-gating (so-called mode 2-gating). Cantharidin inhibited both type 1 and type 2A phosphatase activity in phosphatases purified from guinea pig ventricles [IC50 2.70 (2.06-3.53) and 0.13 (0.05-0.34) microM, n = 5-6, with 95% confidence intervals, respectively]. In isolated [32P]-labeled guinea pig ventricular cardiomyocytes, cantharidin (10 microM) increased the phosphorylation state of phospholamban (to 210% of control), the inhibitory subunit of troponin (to 155% of control), C-protein (to 156% control) and various additional proteins. It is concluded that the effects of cantharidin are likely mediated by increasing the phosphorylation state of several regulatory proteins. Furthermore, cantharidin might be an economical tool to investigate the function of phosphatases in model organ systems.

Animals↗
PubMed1995

[What does the radicality of thyroidectomy depend on?].

Reflections on the radicality of thyroidectomy are based on the persisting lack of uniformity as regards terminology, indications and techniques of thyroid surgery. The authors emphasize four basic factors involved in the solution of thyroid diseases: A. respecting the preoperative examination and recommendations of the endocrinologist, B. philosophy of the surgeon and his workplace, C. experience and skill of the surgeon, D. postoperative follow-up and treatment of patients. The necessity of multidisciplinary collaboration emphasized under A is followed under B by a detailed analysis of principles of the workplace as regards indications and technical and tactical aspects. In part C necessary theoretical and personal problems of the thyroid surgeon are summarized. Without careful postoperative check-up examinations and evaluation of the results of operations mentioned under D we cannot speak of radicality of thyroid surgery.

Humans↗
PubMed1994

In vivo regulation of the mouse beta myosin heavy chain gene.

The interactions of trans-acting factors with their respective cis-acting elements in the 5' upstream region of the beta myosin heavy chain gene (MyHC) regulate its tissue- and developmental stage-specific expression. The role of three conserved elements, an MCAT or TEF-1 binding site, a C-rich region, and a beta e3 region, in muscle-specific gene expression was analyzed in vivo. Each cis-acting site was ablated in the context of the beta MyHC promoter, fused to the chloramphenicol acetyltransferase reporter gene, and used to generate transgenic mice. In contrast to results obtained in vitro, the data demonstrate that mutating any one of these cis-acting elements does not affect the level or tissue specificity of transgene expression. Sequences upstream of -600 can functionally substitute for any one of these regulatory cassettes and are important both for high levels of expression as well as for controlled muscle specificity. Mutation of any two of the cis-acting elements also does not affect transgene expression. However, simultaneous mutation of the three sites significantly reduces expression, indicating that these conserved sequences do play an important role and that combinatorial interactions underlie the beta MyHC's regulation.

Animals↗
PubMed1994

TP53 alterations and clinical outcome in low grade astrocytomas.

Thirty-eight WHO grade II astrocytomas and 10 malignant recurrent gliomas in these patients were examined for the presence of TP53 alterations. Seventeen/38 low grade astrocytomas and 6/10 malignant recurrent tumors harbored mutations of the gene detected by SSCP analysis and direct sequencing of PCR products. TP53 mutations in five out of six high grade mutant tumors were already present in the corresponding low grade astrocytomas. In two cases, TP53 mutations present in the low grade astrocytoma could not be demonstrated in the recurrent glioma. Immunohistochemistry with two different antibodies to the human TP53 protein revealed nuclear immunoreaction of tumor cells in 11/38 low grade and in 8/10 recurrent tumors. There was no correlation between the presence of TP53 alteration and clinical course. We conclude that, although TP53 mutations are detectable in a substantial fraction of WHO grade II astrocytomas, they do not appear to play a role in the malignant progression of these tumors and they are not of prognostic significance.

Amino Acid Sequence↗
PubMed1994

Chirp evoked otoacoustic emissions.

The principles of short frequency sweeps (chirps) and their application to evoke transiently evoked otoacoustic emissions (TEOAE) are developed in comparison to using standard click stimuli. In contrast to click stimuli, chirp signals have the advantage of stimulating a freely selectable frequency range. In addition, chirp signals contain more energy than a click stimulus with the same maximum amplitude. The effects of different stimuli on TEOAE were investigated in normal hearing and hearing-impaired subjects. Using wide-band chirp signals yields a better signal-to-noise ratio compared to click stimulation. In addition, the stimulation of selected regions of the basilar membrane with frequency-limited chirps evokes TEOAE with frequency components that lie within the stimulated frequency range. The characteristic fine structure of this spectrum was found to be independent of the stimulus applied. The utilization of chirp stimuli appears to be useful for evoking TEOAE in, e.g., clinical applications.

Acoustic Stimulation↗
PubMed1994

M2-specific muscarinic cholinergic receptor-mediated inhibition of cardiac regulatory protein phosphorylation.

Acetylcholine acting via muscarinic cholinoceptors decreased phosphorylation of phospholamban and troponin I without reducing adenosine 3',5'-cyclic monophosphate (cAMP) levels or cAMP-dependent protein kinase activity ratio in the presence of 10-100 nM isoproterenol in guinea pig ventricular myocytes. The effect of acetylcholine was more pronounced when adenosine deaminase (5 U/ml) was present and incubation period was short (10 s). Okadaic acid, an inhibitor of protein phosphatase activity, blocked the acetylcholine-mediated inhibition of isoproterenol-stimulated phosphorylation of phospholamban. It is suggested that acetylcholine reduces protein phosphorylation by a cAMP-independent mechanism in guinea pig ventricular myocytes.

Acetylcholine↗
PubMed1994

Biochemical and electrophysiological mechanisms of the positive inotropic effect of calyculin A, a protein phosphatase inhibitor.

Calyculin A (CyA; 1 microM) increased the force of contraction in isolated guinea pig papillary muscles to 144% of control without affecting contraction parameters. The effect of CyA on L-type calcium channels was assessed in cell-attached patches of guinea pig ventricular cardiomyocytes. Unitary Ba++ current recordings revealed that CyA at micromolar concentrations enhanced channel availability almost 2-fold, whereas the duration of individual openings and closures remained unchanged. In whole-cell recordings with Ca++ as the charge carrier, intracellular dialysis of 1 microM CyA enhanced peak current to a similar extent. In homogenates from guinea pig ventricles, 1 microM CyA completely inhibited phosphorylase phosphatase activity. In isolated [32P]-labeled guinea pig ventricular cardiomyocytes, 1 microM CyA increased the phosphorylation state of phospholamban (to 267% of control), that of the inhibitory subunit of troponin (to 182% of control) and those of various additional proteins. We conclude that the effects of CyA are likely to be mediated by increasing the phosphorylation state of several regulatory proteins.

Animals↗
PubMed1994

[Primary and secondary interventions--a concept in surgical documentation].

Nowadays systematic documentation of surgical procedures is absolutely necessary in all departments of surgery and will soon be required by law. Therefore code systems are essential. Amongst numerous systems the ICPM-GE classification has been chosen as basis. In the department for abdominal and transplantation surgery at Hanover Medical School the ICPM-GE classification has been extended by a concept of coding main and suboperations. This concept considers the fact that in an individual patient the surgical procedure may consist of different and standardized suboperations. This concept widens and simplifies the possibility of documentation considerably.

Cholecystectomy↗