[Scientific qualification of nurse-teachers: professionals in nursing--laymen in school?].
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Faculty, Nursing↗
Biomedical subjects
J Neumann
Publications and source records attributed to J Neumann.
Sodium fluoride attenuates the negative inotropic effects of muscarinic M2 and adenosine receptor agonists.
Sodium fluoride increased the force of contraction in isolated guinea-pig papillary muscles concentration dependently, starting at 3 mmol/1. Sodium fluoride inhibited phosphorylase phosphatase activity in homogenates from guinea pig hearts, starting at 1 mmol/1. The positive inotropic effect of 3 mmol/1 sodium fluoride was not accompanied by an increase in cAMP content in guinea-pig papillary muscles. In papillary muscles, carbachol or (-)-N(6)-phenylisopropyladenosine reduced the positive inotropic effect of isoprenaline (10 nmol/1) or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (60 mu mol/1). These negative inotropic effects of carbachol and (-)-N(6)-phenylisopropyladenosine were attenuated by additional sodium fluoride (3 mmol/l). It is concluded that sodium fluoride can impair the signal transduction of muscarinic M2 (carbachol) and adenosine receptor (-)-N(6)-phenylisopropyladenosine) agonists. This effect of sodium fluoride could support the hypothesis that the cardiac effects of muscarinic M2 and adenosine receptor agonists involve, at least in part, the activation of phosphatases.
1-Methyl-3-isobutylxanthine↗
Molecular and physiological effects of overexpressing striated muscle beta-tropomyosin in the adult murine heart.
Tropomyosins comprise a family of actin-binding proteins that are central to the control of calcium-regulated striated muscle contraction. To understand the functional role of tropomyosin isoform differences in cardiac muscle, we generated transgenic mice that overexpress striated muscle-specific beta-tropomyosin in the adult heart. Nine transgenic lines show a 150-fold increase in beta-tropomyosin mRNA expression in the heart, along with a 34-fold increase in the associated protein. This increase in beta-tropomyosin message and protein causes a concomitant decrease in the level of alpha-tropomyosin transcripts and their associated protein. There is a preferential formation of the alpha beta-heterodimer in the transgenic mouse myofibrils, and there are no detectable alterations in the expression of other contractile protein genes, including the endogenous beta-tropomyosin isoform. When expression from the beta-tropomyosin transgene is terminated, alpha-tropomyosin expression returns to normal levels. No structural changes were observed in these transgenic hearts nor in the associated sarcomeres. Interestingly, physiological analyses of these hearts using a work-performing model reveal a significant effect on diastolic function. As such, this study demonstrates that a coordinate regulatory mechanism exists between alpha- and beta-tropomyosin gene expression in the murine heart, which results in a functional correlation between alpha- and beta-tropomyosin isoform content and cardiac performance.
Animals↗
Human heart-infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins.
BACKGROUND: beta-Hemolytic streptococcal infection in developing countries still causes thousands of causes of rheumatic heart disease, demanding surgical valve correction. Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal-M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte-dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions. METHODS AND RESULTS: We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients. We tested their capacity to recognize streptococcal M protein-derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions. Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level. Five of these clones are CD4+, and one is CD8+. CONCLUSIONS: The presence of heart-M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease. The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.
Amino Acid Sequence↗
[Surgical therapy of carcinoma of the thyroid gland].
BACKGROUND: Thyroid carcinoma comprises tumours with a wide spectrum of aggressiveness. The method of first choice is surgery, however, views on its extent and technique are frequently controversial. The objective of the present work was to demonstrate and justify the procedure used at the author's department in treatment of this tumour. METHODS AND RESULTS: During 1988-1992 a total of 919 patients with thyroid disease were operated. The female:male ratio was 4.13:1; a benign finding was confirmed in 76.4% and a malignant one in 23.6%. The female:male ratio in patients with a malignant findings was 3.24:1. Most frequently a papillary carcinoma was confirmed--in 59.9%, followed by follicular carcinoma in 23.11%, medullary carcinoma in 7.0%, Hürtle's carcinoma in 4.25%, anaplastic carcinoma in 1.42% and epidermoid carcinoma in 0.47%. Metastases in the thyroid were present in 0.94% and a myeloma or sarcoma both in 0.47%. In retrosternal goitres papillary carcinoma was most frequent (19 patients) followed by follicular (7 patients). As to surgical operations, total thyroidectomy was performed in 47.6%, total lobectomy in 20.3%, subtotal thyroidectomy in 15.1% and subtotal lobectomy in 2.4% of the operated patients. A palliative resection was made in 11.8% and lymphadenectomy in 2.8% patients with a malignant finding on the thyroid gland. Permanent complications (paresis of the recurrent nerve, hypoparathyroidism) occurred in 0.95% of the patients, temporary complications (abscess in the scar, transient hypoparathyroidism, oedema of the vocal cords) in 8.66% of the operations. None of the patients died. CONCLUSIONS: Surgical results and experience of the clinic for nuclear medicine support a radical approach to all types of thyroid carcinoma in adults as well as in adolescents.
Female↗
Effects of the phosphatase inhibitor calyculin A on the phosphorylation of C-protein in mammalian ventricular cardiomyocytes.
The effects of inhibitors of protein phosphatase activity on C-protein phosphorylation were studied in preparations from mammalian ventricles. Calyculin A (CyA), an inhibitor of type 1 and 2A protein phosphatases, was studied. CyA concentration- and time-dependency increased the phosphorylation state of C-protein in isolated 32P-labelled guinea pig ventricular cardiomyocytes. C-protein was identified by its reaction with a polyclonal antibody and immunoprecipitation. It is concluded that C-protein in intact cardiomyocytes could be a substrate for type 1 and 2A protein phosphatases.
Animals↗
Mechanisms of the contractile effects of flosequinoxan.
In guinea-pig papillary muscles the positive inotropic effect of flosequinoxan (BTS) starting at 100 mumol/l amounted to 287.6 +/- 34.2% at 300 mumol/l without any effects on time to peak tension (103.9 +/- 2%) and relaxation time (107.1 +/- 6.7% of predrug value, respectively). 10 mumol/l carbachol attenuated the positive inotropic effect of 300 mumol/l to 166.5 +/- 11.6% (n = 10). The phosphorylation state of the inhibitory subunit of troponin (TnI) and phospholamban (PLB) in [32P]-labeled guinea-pig ventricular myocytes was increased starting at 100 mumol/l amounting to 142.5 +/- 12.6% and 130.9 +/- 2.2% at 300 mumol/l, respectively (n = 5). Furthermore, BTS (300 mumol/l) decreased phosphorylase phosphatase activity by 23.1%. It is concluded that the contractile effects of BTS are accompanied by enhanced phosphorylation of regulatory proteins which could in part be due to inhibition of phosphorylase phosphatase activity.
Adenosine Triphosphatases↗
[Requirements for a surgical documentation system and its realization].
Adequate documentation of all surgical procedures is now essential. High demands in terms of quality and quantity mean that computerized databases and evaluation procedures are required. In the Department of Abdominal and Transplantation Surgery within Hanover Medical School a standardized but individually adaptable documentation system has been greated using standard hardware and software. A hierarchical code system has been established for surgical procedures, and this also offers the options of automatic online coding and translation into the coding used in the International Classification of Procedures in Medicine. The advantages and limitations of this system are discussed.
Database Management Systems↗
Stimulation of protein phosphatases as a mechanism of the muscarinic-receptor-mediated inhibition of cardiac L-type Ca2+ channels.
Acetylcholine decreases currents through cardiac L-type Ca2+ channels after stimulation with agents which elevate levels of cyclic adenosine monophosphate, such as isoproterenol, but there is still a controversy over the mechanisms of this muscarinic effect. We tested the hypothesis of whether, after isoproterenol stimulation, protein phosphatases are activated by acetylcholine. Whole-cell currents were recorded from guinea-pig ventricular myocytes. The effect of 10(-5) M acetylcholine on currents induced by 10(-8) M isoproterenol was studied in the absence or presence of protein phosphatase inhibitors. Three agents reduced the acetylcholine response: okadaic acid (3 or 9 x 10(-6) M) and cantharidin (3 x 10(-6) M) added to the pipette solution, and bath-applied fluoride (3 mM). In contrast, pipette application of other phosphatase inhibitors, namely the inhibitor PPI2 (1000 U/ml), ciclosporin (10(-5) M), or calyculin A (10(-6) M) did not significantly diminish the acetylcholine effect. Interestingly, there was no correlation between the effects of the compounds on basal Ca2+ current and their interference with the muscarinic response. An activation of type 2A phosphatases by acetylcholine would explain these findings. Indeed, okadaic acid is 3 orders of magnitude more potent in vitro in its inhibition of this isoform (purified from cardiac myocytes) than is calyculin A, while type-1 phosphatases are inhibited equally. The data support the attractive possibility that stimulation of protein phosphatases is part of the signal transduction cascade of Ca2+ channel inhibition by acetylcholine.
Acetylcholine↗
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↗
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↗
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↗
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↗
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↗
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↗
Kidney allograft outcome analyzed by donor-reactive antibodies after transplantation.
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Adolescent↗
[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↗
Recurrent focal glomerulosclerosis in renal allografts.
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Adolescent↗