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Biomedical subjects

U Mende

Publications and source records attributed to U Mende.

At least 55 records · Page 3Linked to original sources
PubMed1992

Long term beta-adrenoceptor-mediated up-regulation of Gi alpha and G(o) alpha mRNA levels and pertussis toxin-sensitive guanine nucleotide-binding proteins in rat heart.

Chronic stimulation of beta-adrenoceptors leads to increased mRNA and protein levels of pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in the heart. In the present study the time course is reported of the effect of isoprenaline infusions on myocardial mRNA levels of Gi alpha-2, Gi alpha-3, G(o) alpha, Gs alpha, and G beta and myocardial levels of PTX-sensitive G proteins. Rats were treated by subcutaneous infusions, with osmotic minipumps, of 0.9% NaCl, isoprenaline (2.4 mg/kg/day), propranolol (9.9 mg/kg/day), or a combination thereof for 1, 2, 3, 4, or 8 days, and two groups were treated with NaCl or isoprenaline for 13 or 26 days. Additional groups of rats were treated with 0.24 or 0.07 mg/kg/day for 4 days to determine the dose dependency of the effects of isoprenaline. mRNA concentrations were determined by standardized slot blotting with 32P-labeled cDNA or cRNA probes. In isoprenaline-treated rats, mRNA levels of all members of the Gi alpha/G(o) alpha family increased gradually in parallel. The increase in Gi alpha-2, Gi alpha-3, and G(o) alpha mRNA levels reached significance on days 2-3, reached maximal values on days 3-4, and remained stable over the total time of treatment of up to 26 days. Compared with NaCl, maximal increases were 77% (Gi alpha-2; 16.4 versus 9.3 pg/micrograms), 58% (Gi alpha-3; 4.65 versus 2.95 pg/micrograms), and 78% (G(o) alpha; 0.40 versus 0.22 pg/microgram). Gs alpha mRNA levels (about 30 pg/micrograms) and G beta mRNA levels remained unchanged. In isoprenaline-treated rats myocardial levels of PTX-sensitive G proteins increased by maximally 54%, compared with control. The time course differed slightly from the time course of mRNA up-regulation in the first 3 days of treatment and paralleled the increase in mRNA levels from day 4 on. Propranolol had no effect on G alpha mRNA or protein levels when given alone but abolished all effects of isoprenaline when given in combination. Isoprenaline at a dose of 0.24 mg/kg/day still induced an increase in Gi alpha-2 mRNA levels of 24%, without any effects on histopathology of the myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Phosphodiesterase inhibition by enoximone in preparations from nonfailing and failing human hearts.

The effects of enoximone (MDL 17043, Perfan, CAS 77671-31-9) on the activities of the phosphodiesterase (PDE) isoenzymes I-IV and on force of contraction were investigated in ventricular preparations isolated from failing (end-stage myocardial failure, NYHA IV) and non-failing human hearts. In both tissues four PDE isoenzymes (PDE I-IV) with similar properties were separated by DEAE-sepharose chromatography. The effects of enoximone on PDE I-IV activities did not differ between non-failing and failing human hearts. As compared to PDE I (IC50 2100 mumol/l) and II (IC50 2900 mumol/l) enoximone is a selective PDE III (cGMP-inhibited PDE, IC50 5.9 mumol/l) and PDE IV (cGMP-insensitive PDE, IC50 21.1 mumol/l) inhibitor. Milrinone, 3-isobutyl-1-methylxanthine (IBMX) and UD-CG 212 Cl, a derivative of pimobendan, were studied in the failing heart for comparison. Milrinone inhibited PDE I-IV activities similar to enoximone, revealing IC50 values for inhibition of PDE III and IV (1.2 and 3.3 mumol/l) which were about two orders of magnitude lower than that of PDE I and II (173 and 306 mumol/l). UD-CG 212 Cl was the most potent (IC50 0.05 mumol/l) and most selective PDE III inhibitor tested (IC50 for PDE I, II and IV were 175, 181 and 40.8 mumol/l, resp.), whereas IBMX inhibited PDE I-IV nonselectively (IC50 15.3, 26.2, 5.6, 5.8 mumol/l, respectively). In trabeculae carneae from nonfailing and failing human hearts enoximone increased force of contraction only marginally by 18.0 +/- 9.1% (n = 8) and 24.5 +/- 8.7% (n = 9) of the predrug value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[The radiotherapy of Castleman's lymphoma].

The angiofollicular lymphoid hyperplasia, first described by Castleman, is a benign lymphoma. The authors report a very rare case of Castleman lymphoma in the parotid gland. The tumor was successfully irradiated with 40 Gy fast electrons. Treatment planning and therapy monitoring were done by means of ultrasound and computed tomography.

Adult↗
PubMed1992

[Sonography in therapy-oriented diagnosis and after-care of primary bone and soft tissue tumors].

Based on the results of 150 patients with primary tumors or the suspicion of malignant lesions of the locomotor system the perspectives and limits of the sonographic diagnosis under the therapeutic aspects of interdisciplinary oncologic cooperation is demonstrated. As the ideal adjunct to conventional roentgenograms, ultrasound is the first-line imaging procedure in the fields of primary diagnosis, follow-up, post-therapeutic care as well as tumor exclusion for methodic, patient-related and economic/logistic reasons. Its consequent application will markedly reduce the number of more invasive and expensive methods.

Adult↗
PubMed1991

Mechanism underlying the reduced positive inotropic effects of the phosphodiesterase III inhibitors pimobendan, adibendan and saterinone in failing as compared to nonfailing human cardiac muscle preparations.

The present study was performed to compare the effects of the new positive inotropic phosphodiesterase III inhibitors pimobendan, adibendan, and saterinone on the isometric force of contraction in electrically driven ventricular trabeculae carneae isolated from explanted failing (end-stage myocardial failure) with those from nonfailing (prospective organ donors) human hearts. In preparations from nonfailing hearts the phosphodiesterase inhibitors, as well as the beta-adrenoceptor agonist isoprenaline, the cardiac glycoside dihydro-ouabain, and calcium, which were studied for comparison, revealed pronounced positive inotropic effects. The maximal effects of pimobendan, adibendan, and saterinone amounted to 56%, 36% and 45%, respectively, of the maximal effect of calcium. In contrast, in preparations from failing hearts the phosphodiesterase III inhibitors failed to significantly increase the force of contraction and the effect of isoprenaline was markedly reduced. The effects of dihydroouabain and calcium were almost unaltered. The diminished effects of isoprenaline were restored by the concomitant application of phosphodiesterase inhibitors. To elucidate the underlying mechanism of the lack of effect of the phosphodiesterase III inhibitors in the failing heart we also investigated the inhibitory effects of these compounds on the activities of the phosphodiesterase isoenzymes I-III separated by DEAE-cellulose chromatography from both kinds of myocardial tissue. Furthermore, the effects of pimobendan and isoprenaline on the content of cyclic adenosine monophosphate (determined by radioimmunoassays) of intact contracting trabeculae were studied. The lack of effect of the phosphodiesterase inhibitors in failing human hearts could not be explained by an altered phosphodiesterase inhibition, since the properties of the phosphodiesterase isoenzymes I-III and also the inhibitory effects of the phosphodiesterase inhibitors on these isoenzymes did not differ between failing and nonfailing human myocardial tissue. Instead, it may be due to a diminished formation of cyclic adenosine monophosphate in failing hearts, presumably caused mainly by a defect in receptor-adenylate cyclase coupling at least in idiopathic dilated cardiomyopathy. Both the basal and the pimobendan-stimulated or isoprenaline-stimulated contents of cyclic adenosine monophosphate of intact contracting trabeculae from failing hearts were decreased compared with the levels in nonfailing hearts. However, under the combined action of isoprenaline and pimobendan the cyclic adenosine monophosphate level reached values as high as with each compound alone in nonfailing preparations, and in addition the positive inotropic effect of isoprenaline was restored. These findings may have important clinical implications. Along with the elevated levels of circulating catecholamines the positive inotropic effects of the phosphodiesterase inhibitors may be maintained in patients with heart failure.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1991

Isoprenaline-induced increase in mRNA levels of inhibitory G-protein alpha-subunits in rat heart.

Long-term beta-adrenergic stimulation has been shown to desensitize the beta-adrenoceptor/adenylyl cyclase signalling pathway at both the receptor and the G-protein level. To further elucidate the cellular mechanism of G-protein regulation we investigated the influence of prolonged infusion of isoprenaline (2.4 mg/kg.d) on myocardial mRNA levels of different G-protein alpha-subunits in rats. For comparison rats were treated with triiodothyronine (T3; 0.5 mg/kg.d) which induces cardiac hypertrophy like isoprenaline but has different effects on the adenylyl cyclase system. Isoprenaline- and T3-treated animals developed an increase in heart/body weight ratio of 41 +/- 3% and 27 +/- 4%, respectively (P less than 0.05). Isoprenaline increased myocardial total RNA concentration by 39 +/- 6% (P less than 0.05). Hybridization with 32P-labeled rat cDNAs demonstrated an expression rank order of Gs alpha-mRNA greater than Gi alpha-2-mRNA greater than Gi alpha-3-mRNA and no detectable expression of Gi alpha-1-mRNA in rat myocardium. mRNA levels of Gs alpha, Gi alpha-2 and Gi alpha-3 were 36.9 +/- 1.28, 10.7 +/- 1.07 and 3.7 +/- 0.19 pg/micrograms total RNA, respectively. Isoprenaline increased Gi alpha-2- and Gi alpha-3-mRNA concentrations per microgram total RNA by 49 +/- 18% and 27 +/- 7%, respectively (P less than 0.05). This effect was abolished by simultaneously administered propranolol (9.9 mg/kg.d), indicating a beta-adrenoceptor-mediated mechanism. In contrast, T3-induced cardiac hypertrophy was not accompanied by changes in Gi alpha-mRNA expression. Gs alpha-mRNA levels were unaffected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Beta-adrenoceptor stimulation-induced increase in cardiac Gi-protein expression and in carbachol sensitivity.

Increased plasma concentrations of catecholamines are assumed to be responsible for the decreased sensitivity to catecholamines of the failing heart. We investigated in rat heart the influence of a 4-day infusion of isoprenaline (Iso; 2.4 mg.kg-1.d-1), propranolol (Prop; 9.9 mg.kg-1.d-1), Iso + Prop or 0.9% NaCl as control (Ctr) on myocardial Gi-mRNA and Gi-protein levels and on the negative inotropic effect of carbachol in papillary muscles. In Iso-treated rats, hybridization experiments with 32P-cDNAs revealed a 49 +/- 18% (n = 7-8) and 27 +/- 7% (n = 8) increase in Gi alpha-2- and Gi alpha-3-mRNA respectively, and pertussis toxin-catalyzed ADP-ribosylation revealed a 22 +/- 7% (n = 8) increase in Gi-protein as compared to Ctr. These alterations were accompanied by an increased potency of carbachol (mean EC50: 0.04 microM vs. 0.28 microM) in the presence of Iso in isolated electrically driven (1 Hz) papillary muscles. Prop had no effect on Gi-protein expression but antagonized all Iso-induced effects. In conclusion, beta-adrenergic stimulation leads to an increased expression of Gi and to an enhanced negative inotropic potency of muscarinic agonists. An enhanced muscarinic receptor coupling via Gi might play a pathophysiological role in heart diseases with increased plasma catecholamine levels.

Animals↗
PubMed1991

The role of alpha 1-adrenergic and muscarinic receptors in cardiac function.

The positive inotropic effect of an alpha 1-adrenoceptor agonist, such as phenylephrine, is accompanied by an increase in the presumed second messenger, inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4), which may release calcium from the sarcoplasmic reticulum (SR) and/or facilitate calcium entry from the extracellular space. In addition, phenylephrine sensitizes the contractile proteins for calcium. Alpha 1-adrenergic positive inotropic effects are enhanced in heart muscle preparations from cardiomyopathic hamsters and are reduced in heart muscle preparations from human failing myocardium. How the negative inotropic effects of M-cholinoceptor agonists work in the presence of cAMP-increasing agents in ventricular heart muscle preparations is discussed. It involves cAMP-reduction, an increase in cGMP and activation of phosphatase activity. In a rat model, chronic beta-adrenergic stimulation leads to increased sensitivity of rat ventricular tissue for the negative inotropic effect of the M-cholinoceptor agonist, carbachol. This might be due to facilitated signal transduction via increased Gi proteins. In human ventricular tissue from hearts with end-stage heart failure, due to idiopathic dilated cardiomyopathy (IDC), an increased Gi protein has also been found. However, the negative inotropic effects of carbachol were unchanged. The data indicate that changes in alpha-adrenergic and M-cholinergic responses in the heart may depend on underlying causes that induce changes.

Animals↗
PubMed1991

Effects of isomazole on force of contraction and phosphodiesterase isoenzymes I-IV in nonfailing and failing human hearts.

The phosphodiesterase (PDE) inhibitor isomazole increased the force of contraction to 278.3 +/- 89.1% (n = 7) of the predrug value in ventricular trabeculae carneae isolated from nonfailing human hearts. This effect can be attributed mainly to a PDE III or a combined PDE III/IV inhibition since at the concentration of the maximal positive inotropic effect of isomazole, PDE III and PDE IV were completely inhibited. In explanted failing human hearts (end-stage myocardial failure, NYHA IV), isomazole increased the force of contraction only marginally to 110.1 +/- 10.7% of the predrug value. The lack of a distinct positive inotropic efficacy of isomazole in failing human hearts could not be explained by an impairment of PDE inhibition since the properties of the PDE I-IV isoenzymes separated by DEAE-Sepharose chromatography and the inhibitory effects of isomazole did not differ in both preparations. The positive inotropic effect of the beta-adrenoceptor agonist isoprenaline was also reduced in failing hearts. However, in the presence of isomazole, the diminished positive inotropic effect of isoprenaline was restored to values obtained with isoprenaline alone in nonfailing hearts. Thus, the decreased effect of inotropic drugs like isoprenaline or isomazole in preparations from failing human heart might be explained mainly by a diminished cAMP formation due to a defect in receptor-adenylate cyclase coupling.

Adult↗
PubMed1990

[Value of squamous cell epithelial-associated (SCC-) antigens in early diagnosis of oral carcinoma].

The diagnostic value of plasma concentration of the squamous cell carcinoma antigen was examined in 75 cases of pretherapeutic squamous cell carcinoma of the oral cavity. A pathologic plasma level was found in 32% of the tumour patients at time of diagnosis. The incidence of elevated SCC- values was inversely correlated to the tumour grading. A direct correlation of the sonographically measured total tumour volume was seen. As predominantly more extended tumours show pathologic values, SCC-Antigen is not a marker for the screening in the diagnosis of the early cancer of oral cavity. That emphasizes the importance of the precise clinical examination of each patient. In cases of elevated pretherapeutic values SCC-Antigen is very useful for therapy--monitoring and follow-up.

Antigens, Neoplasm↗
PubMed1990

[Esthesioneuroblastoma--treatment of recurrences using the remote-control afterloading technic. A case report].

At the Radiological Hospital of the Heidelberg University, one patient with a local recurrence of an esthesioneuroblastoma situated on the left-hand side of the skull base was treated between February 11 and March 18, 1986, by an afterloading contact therapy with curative intent. After preceding surgery and percutaneous radiotherapy, repeated local recurrences and locoregional lymph node metastases had occurred. The contact therapy was performed after adjusting an individual face mask in which the afterloading probe was placed and brought into its position in the tumor region. The irradiation scheme was based on the transformation of the source coordinates form the stereoscopic X-ray localization system into the coordinate system of the computed tomogram by means of X-ray tight reference points. The irradiation planning by computed tomography allows to optimize the arrangement of sources within the tumor region. The principles of the method as well as the treatment result are presented.

Brachytherapy↗
PubMed1989

[Detection and assessment of cervical lymph node metastases in head-neck tumors. A comparison of methods].

From 1984 to 1987, seventy-two patients with squamous cell carcinomas involving oropharynx, hypopharynx, larynx and cervical lymph nodes, who underwent surgery, were examined to determine the value of computed tomography (CT), magnetic resonance (MR), high-resolution real-time sonography (US) and palpation in preoperative staging of cervical nodal metastases. The clinical staging was compared with the microscopic findings in the neck specimens and with operative reports. For the identification and description of cervical lymph node metastases, US and CT are more valuable than MR and palpation. In comparison to CT, however, US has advantages in most cervical areas as a dynamic method with variable representation of interesting regions. False positive errors are related to confusion with inflammatory nodes in all examinations. Metastatic infiltration of surrounding tissue especially of neck vessels, are best recognised by means of US and MR. However, the high rates of sensitivity and low rates of specificity of all methods point to the possibility of a great number of false positive errors in demonstrating tissue infiltration.

Angiography↗
PubMed1989

[Diagnosis of luxation-fracture of mandibular condyle].

Based on an unusual case of bilateral mandibular condyle fracture the diagnostic problems are described. If conventional X-ray, panorama-tomograms and bilateral tomograms of both temporomandibular joints do not exactly show the fracture dislocation and the relation of the fragments CT scans should be taken.

Adolescent↗
PubMed1989

[Sonographic diagnosis of head and neck tumors in association with therapy].

Basing on the experience with 558 patients suffering from tumours or suspicious lesions in the head and neck region, sonographic pointers that have been inadequately noted so far, are pointed out to improve diagnosis, follow-up, and post-therapeutic care. Among the possibilities offered by sonography are: to confirm or exclude bony involvement of the mandible in tumours of the oral cavity and the oropharynx, to objectify the results of antineoplastic chemotherapy, to offer possibilities to optimize radiotherapy, as well as to show criteria for the early detection of a relapse under consideration of the primary therapy.

Adolescent↗
PubMed1989

[Radiologic diagnosis of bone metastases].

The diagnostic relevance of the various radiological examination methods - skeleton scintigraphy, conventional x-ray film, computed tomography, sonography and magnetic resonance - was analysed on the basis of an examination of 4765 clinically or scintigraphically suspect skeleton segments in order to arrive at an effective but also economically justifiable diagnostic approach. Conventional skeleton scintigraphy should be employed as the first method of choice, since it has a sensitivity of 93% and is hence very suitable as a searching tool. To differentiate benign and malignant lesions it is absolutely imperative to conduct at the same time a x-ray control of any abnormal accumulation of nuclides, or of parts of the skeleton that display signs or symptoms. Conventional x-ray film diagnosis enabled correct diagnosis of the type of disease in 95% of the cases. In its capacity as a complementary examination method, computed tomography enabled correct diagnosis in 52% of the cases that had remained roentgenologically unclear. A pathological bone scintigram without any x-ray or CT correlate must be considered as being suspect of metastases if trauma is absent. Magnetic resonance proved to be the most sensitive method in identifying malignant infiltrations of the medullary space in two patients suffering from a clearly delineated pain syndrome with normal x-ray and CT findings. Sonography proved superior in detecting extraosseous tumour portions. The value of angiography is the preoperative vascular imaging of metastases of the possibility of performing therapeutic embolisation or intraarterial drug therapy.

Angiography↗
PubMed1989

[Realtime sonography].

Between March 1985 and March 1988 109 patients with tumours of the oral cavity and the oropharyngeal region underwent 123 examinations by orthopantomography and realtime sonography for primary staging and/or diagnosis of a recurrent disease. In 105 cases the preoperative results could be compared to intraoperative and histopathological findings. Realtime sonography as a noninvasive, inexpensive and efficient method offered the ideal diagnostic adjunct to the orthopantomogram. Not only size, shape and structure of the soft tissue tumour could be accurately defined; whatsmore it was possible to demonstrate its relation to bony structures and to a high degree of sensitivity cortical invasion and periosteal reaction. The limitations of the method especially the risk of false positive findings after invasive diagnostic and therapeutic procedures are pointed out.

Humans↗
PubMed1989

[Accelerated irradiation of bone metastases].

In a prospective study, accelerated irradiation was performed over 60 portals in 34 tumor patients with peripheral bone metastases. During a period of three days, three daily fractions of 3 Gy each were applied with intervals of four hours, resulting in a total dose of 27 Gy. Using this fractionation schedule introduced by Ammon, a reduction of metastasis-associated pain was achieved in 90% of cases (54/60). The onset of pain reduction was observed earlier than seen with conventional fractionation schedules (five fractions of 2 Gy each per week, total dose 40 Gy). With regard to objective treatment effects, no significant difference was found between accelerated irradiation and conventional fractionation, the rate of remineralization being 43% (26/60), and the rate of stabilization of formerly progressive bone destructions being 55% (33/60). Accelerated irradiation was tolerated well usually. Marked acute side reactions occurred in only one case with metastatic involvement of joint and reaction of synovia. The major advantage of accelerated irradiation is the shortening of the total treatment period and the consequent reduction of treatment stress in patients with advanced cancer.

Adult↗