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M Neuss

Publications and source records attributed to M Neuss.

At least 37 records · Page 2Linked to original sources
PubMed1995

Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts.

BACKGROUND: To assess the chamber localization, subtype distribution, and regulation of human myocardial angiotensin II receptors in heart failure, we determined the binding of angiotensin II, Sar1Ile8-angiotensin II, and the subtype-specific antagonists Dup 753 (AT1-specific) and PD 123319 (AT2-specific) in atria from patients with normal (left ventricular ejection fraction > 55%) or moderately impaired (left ventricular ejection fraction 30% to 55%) cardiac function and in atria and ventricles from explanted end-stage failing hearts. Sarcolemmal and combined fractions, the latter including internalized receptors, were studied. In addition, AT1 mRNA content was analyzed by polymerase chain reaction after reverse transcription. METHODS AND RESULTS: The number of angiotensin II binding sites (Bmax) in sarcolemmal fractions was significantly reduced in explanted end-stage failing hearts in comparison with control subjects and moderate heart failure (Bmax 3.9 +/- 0.8 versus 11.2 +/- 1.7 and 9.6 +/- 0.8 fmol/mg protein, respectively). A comparable 65% reduction in receptor numbers was found in combined fractions from end-stage failing hearts, indicating that the loss of binding sites was not due to their internalization. The dissociation constants were comparable in sarcolemmal and combined fractions and in nonfailing and failing hearts, ranging from 0.5 +/- 0.2 to 1.2 +/- 0.5 nmol/L. In nonfailing hearts, 69 +/- 4% of binding sites were blocked by the subtype-2-specific inhibitor PD 123319 and were therefore classified as AT2; 33 +/- 5% were blocked by the subtype-1-specific inhibitor DUP 753 and thus classified as subtype 1. In explanted hearts, comparable ratios of 66 +/- 5% AT2 sites and 34 +/- 5% AT1 sites were found. AT1 cDNA amplification signals by polymerase chain reaction were reduced to about one third of the level in control subjects in end-stage failing hearts. CONCLUSIONS: Angiotensin II receptors in human myocardium are present in relatively low numbers, and AT2 is the predominant subtype. A significant loss of angiotensin II receptors occurs in end stage but not in moderate heart failure. The loss of receptors affects both subtypes to a comparable degree. The data suggest that the decrease in receptor density is due to a decrease in steady-state mRNA abundance.

Binding Sites↗
PubMed1995

Chamber-specific expression of human myocardial proteins detected by two-dimensional gel electrophoresis.

High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), followed by computer-assisted image analysis (PDQUEST) was used to screen atrial and ventricular protein patterns for quantitative and qualitative differences in protein expression. Myocardial proteins from left ventricular (LV) and right atrial (RA) samples from end-stage, failing explanted hearts and from a healthy donor heart (control) were separated by 2-D large gel electrophoresis. Ten RA versus ten LV gels from explanted dilated cardiomyopathic (DCM) hearts were analyzed for quantitative differences in their spot patterns. Of the 197 spots matched to every gel, 40 spots differed significantly in intensity between RA and LV for DCM patients. A larger number of atrial and ventricular gels (20 RA, 20 LV) from DCM patients and from a healthy donor heart (4 RA, 4 LV gels) were analyzed for qualitative differences in protein expression. Three protein spots (SSP 1120: M(r)/pI:20.5 kDa/4.6; SSP 1119: M(r)/pI:20.6 kDa/4.5; SSP 0117:M(r)/pI:20.7/ < 4.5) that are present in all RA gels for DCM patients are absent in all LV gels. Two protein spots (SSP 0112: M(r)/pI:17.2 kDa,/ < 4.4; SSP 0114:M(r)/pI:17.6 kDa/ < 4.4) occur only in all LV gels but not in the RA gels. These five qualitatively differing spots are identical in DCM patients and in the healthy donor heart. Some of the differing spots were internally sequenced and identified as myosin light chain isoforms (myosin light chain 2, atrial; myosin light chain 2, ventricular; myosin light chain 1, atrial) with the Protein Identification Resource (PIR) accession numbers A44451, S03708, A30881, respectively. Additionally, phosphoglycerate mutase (PIR: JQ0750) and ATP synthase alpha chain (PIR: S17193) were identified. Thus, quantitative and qualitative differences between atrial and ventricular protein patterns were identified by 2-D PAGE. A characteristic distribution of myosin light chains between atrial and ventricular human myocardium was found using our approach.

Amino Acid Sequence↗
PubMed1995

Effects of angiotensin receptor antagonists in heart failure: clinical and experimental aspects.

In addition to inhibition of the circulating renin-angiotensin system, specific inhibition of the cardiac effects of angiotensin II (Ang II) represents an important therapeutic goal in the treatment of clinical heart failure. Subtype 1-specific Ang II receptor (AT1) antagonists have been developed to overcome potential limitations of angiotensin converting enzyme inhibitors, e.g. insufficient control of tissue Ang II production and bradykinin-related side effects. Clinical studies have demonstrated beneficial effects of AT1 antagonists. In a single-dose study, the AT1 antagonist losartan decreased the mean arterial pressure and pulmonary arterial pressure while increasing the cardiac index. Effects were dose dependent. Haemodynamic effects were greater with higher doses, but neurohormonal counter-regulation probably also increased, leading to relatively high levels of circulating Ang II with the 150-mg dose, A decrease in plasma levels of noradrenaline, atrial natriuretic factor, and aldosterone reached partial significance. Administration of multiple doses of losartan for 12 weeks also led to favourable haemodynamic and clinical results. Arterial blood pressure, pulmonary capillary wedge pressure, and systemic vascular resistance decreased. The neurohormonal effects of 12 weeks' administration of AT1 antagonists consisted in a decrease in plasma aldosterone concentrations. Whereas AT1 antagonists may counteract the effects of Ang II on the vasculature, and therefore are effective vasodilators, their direct myocardial effects are less clear. The subtype AT2, which represents the dominant, receptor in both healthy and failing human myocardium, is not blocked by AT1 inhibition. Angiotensin receptors on isolated human cardiac fibroblasts stimulate cellular proliferation via a yet undertermined receptor subtype. AT1 antagonists exert beneficial haemodynamic and neurohormonal effects in human heart failure. Their direct myocardial effects require further investigation.

Angiotensin Receptor Antagonists↗
PubMed1995

[Angiotensin receptors--organ and subtype specific regulation in cardiovascular diseases by modulation of the renin-angiotensin system. Studies of the rat model and in human myocardium].

So far, two angiotensin receptor subtypes, called AT1 and AT2, have been described in an animal model and in human. AT1 mediates almost all known effects of angiotensin II and its gene sequence and regulation is well studied. In contrast, only few data on function and regulation of AT2 are available. The complete mRNA sequence of AT2 has only recently been cloned and sequenced. The angiotensin receptors' receptor density and subtype distribution is organ specific. In the rat, lowest densities are found in the myocardium, followed by kidney, liver, adrenal medulla and cortex. The percentage of AT1 in the different organs amounts to 80, 85, 90, 57 and 10%. Angiotensin receptor subtypes have also been quantitated in human myocardium. There, the relatively unknown subtype AT2 dominates (67%). Myocardial receptor density is low, amounting to about 11 fmol/mg protein corresponding to 1/20-1/50 of the density of beta-adrenergic receptors. Angiotensin receptors in the human heart are present on cardiac fibroblasts and induce proliferation of these cells. Blockade of the renin angiotensin system by ACEI and AT1 antagonists in the rat downregulates angiotensin receptors in liver, kidney and adrenals to about 50% in an organ- and subtype specific manner, whereas cyclosporin A upregulates receptors twice. In end-stage human heart failure, but not in early stages, angiotensin receptors are downregulated to 1/3 of control values. Regulator mechanisms at transcriptional level have been elucidated by reporter gene assays; PMA, an activator of proteinkinase C, stimulates the transcription of the AT1 gene. The organ- and subtypespecific regulation of angiotensin receptors by pharmacological agents and/or cardiovascular diseases can contribute to the understanding of these drugs and of the pathophysiology of the corresponding diseases.

Animals↗
PubMed1994

Human cardiac fibroblasts express an angiotensin receptor with unusual binding characteristics which is coupled to cellular proliferation.

To assess the cellular localization of angiotensin receptors in human heart, we isolated human cardiac fibroblasts from explanted end-stage failing human hearts. As judged by an immunofluorescence assay, the isolated cells consisted of 96% of fibroblasts. Using receptor binding studies, we could identify a single angiotensin binding site on these cells, with a Kd of 0.6nM and a Bmax of 1.5 fmol/mg protein. Inhibiting concentrations 50 for Ang II and Ang I/II (1-7) were 40nM and 10nM, respectively. Stimulation with Ang II (100 nM) and Ang I/II (1-7) (100nM) led to cellular proliferation which could not be inhibited by Losartan or PD 123319. These results suggest that human cardiac fibroblasts express an as yet unknown angiotensin receptor-subtype.

Angiotensin II↗
PubMed1994

Regulation of the angiotensin receptor subtypes in cell cultures, animal models and human diseases.

With the development of subtype specific angiotensin II (Ang II) receptor antagonists and their introduction into the treatment of heart failure and hypertension, the regulation of the Ang II receptor with its subtypes AT1 and Ang T2 gains clinical importance. In cell cultures, the number of surface AT1 is clearly down-regulated by Ang II exposure. Down-regulation can be due to reversible internalization, to phosphorylation and to reduced synthesis and involves protein kinase C and phospholipase C mediated pathways. In this respect, the AT1 behaves as a typical G-protein coupled receptor. Aldosterone, cAMP, norepinephrine and extracellular glucose concentrations can contribute to AT1 regulation. There are very few data regarding the regulation of the subtype AT2, indicating modulation by a number of growth factors and by Ang II. In whole animal models receptor regulation deviates partially from cell cultures. In the rat, the two subtypes AT1A and AT1B are differentially regulated and the expression of subtypes is organ specific. In most experiments, including our own experiences, the AT1, in the adrenals was up-regulated by Ang II infusion and down-regulated by angiotensin converting enzyme inhibitors (ACEI) or Ang II receptor antagonists. Differing effects were observed in other organs. In humans, a number of studies seeking an association between Ang II levels, Ang II receptor regulation and physiological events have been conducted in platelets. In pregnant women, a negative correlation between plasma Ang II levels and Ang II binding and an association between receptor regulation and pregnancy-induced hypertension has been described.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Evidence that Borrelia burgdorferi immunodominant proteins p100, p94 and p83 are identical.

Recently there have been reports on high-molecular mass components of Borrelia burgdorferi, namely the p100, p94 and p83, which claimed these proteins to be specific marker antigens for the serodiagnosis of late Lyme borreliosis. The nucleotide sequences of the p100 and p83 have been published. The alignment of the deduced N-terminal amino acid sequences with the N-terminal sequence of the p94 now provides evidence that all three proteins are identical.

Amino Acid Sequence↗
PubMed1992

[Nodular panniculitis: a manifestation of Lyme borreliosis?].

Infection with Borrelia burgdorferi can induce various skin manifestations. The type of skin manifestation and the histopathological picture depend on the stage of infection and vary from local inflammatory infiltrates to chronic atrophic skin disease. Involvement of subcutaneous tissue has been observed only very rarely. We report on two patients suffering from nodular panniculitis (Pfeifer-Weber-Christian) and present evidence that the disease was caused by Borrelia burgdorferi. In one of the cases Borrelia burgdorferi was repeatedly isolated from skin and subcutaneous tissue biopsies in spite of repeated high-dose therapy with ceftriaxone, Doxycycline and cefotaxime.

Adult↗
PubMed1988

Intramedullary spinal cord tumors resected with CO2 laser microsurgical technique: recent experience in fifteen patients.

We have operated upon 15 intramedullary spinal cord tumors with the aid of a CO2 laser attached to the microscope. The operative technique is described. Most of the tumors were localized within the cervical spinal cord. Nine tumors were benign gliomas: 4 ependymomas, 1 subependymoma, 3 astrocytomas, and 1 ganglioglioma. Six were removed totally, and 3 were removed subtotally. The remaining 6 tumors consisted of 3 hemangioblastomas, 1 intramedullary neurofibroma, 1 lipoma, and 1 primary intramedullary melanoma. Neurological function postoperatively compared to the preoperative function of the upper extremities was unchanged in 13 patients (86.5%), improved in 1, and worse in 1 patient. In the lower extremities, the preoperative neurological status was unchanged in 11 patients (73.3%), improved in 1 patient, and worse in 3 patients (20%). Magnetic resonance imaging was superior to myelography and computed tomography in localizing these lesions. Enhancement with paramagnetic substances (e.g., gadolinium-DTPA) helps to localize solid tumor within cysts. Histological evaluation of small tissue biopsies or frozen section histology is unreliable. The entire lesion should be exposed in all cases, and an attempt should be made to remove the tumor totally or, if this is not possible, to resect as much of the center of the tumor as is possible until the cord is decompressed. The decision to administer further treatment is based on the histological features of the tumor.

Adolescent↗
PubMed1988

Clinical and laboratory findings in patients with multiple meningiomas.

A series of eight patients with multiple meningiomas is presented. Up to 14 meningiomas were diagnosed in one patient. The clinical and laboratory findings suggest that multiple meningiomas do not constitute a disease entity of their own featuring disease-specific clinical or laboratory findings. In our series we find a female predominance with seven female and one male patient. The histological findings were mixed, even within the individual cases. There are no consistent patterns of steroid receptor levels or chromosomal aberrations in the more recent cases in which these parameters could be investigated.

Adult↗
PubMed1987

Does the timing of aneurysm surgery neglect the real problems of subarachnoid haemorrhage?

In 1984, in connection with the introduction of the calcium antagonist nimodipine, a new strategy for the treatment of subarachnoid haemorrhage (SAH) due to ruptured aneurysm was developed in our hospital. With no rigid regard to "timing" all patients undergo surgery as soon as possible. The only exception being those in Hunt and Hess grades IV and V without space-occupying intracranial haemorrhage and those bearing aneurysms of the vertebrobasilar circulation that are difficult of access. As soon as the risk of rebleeding has been eliminated surgically an active therapy against the possible consequences of SAH--cerebral vasospasm and simultaneous disturbances of autoregulation--is started. It consists in lowering the increased intracranial pressure, raising of mean arterial pressure and improving of rheological properties of the blood in order to prevent delayed build-up of neurological deficit due to ischaemia. It goes without saying that calcium antagonists are given from the very beginning of the patient's treatment even before operation. The advantages of this therapeutic concept are demonstrated by two series of non-selected consecutive patient material. The first series (A; n = 135) was treated between 1981 and 1984 before the change in treatment strategy, the second (B; n = 183) from 1984 to 1986 after that change. The overall mortality in series A was 27%, that in series B 20%. Operative mortality could be reduced from 22% to 16% in patients having undergone early operation and from 6% to 2% in patients with late surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Prostaglandins: antiproliferative effect of PGD 2 on cultured human glioma cells.

Five cultured human glioma cell lines were investigated for their reaction to prostaglandin (PG) D2 and E2. In all cases a suppressive effect on DNA synthesis as assessed by 3H-thymidine incorporation was seen with all test substances as early as six hours after the addition of the compounds in doses of usually 10(-5) M. A dose response curve was generated in four cases and showed an estimated ED 50 of about 5 X 10(-6)M. The effect was most pronounced at 12 hours after which the cultures began to recover except those which had been incubated with PGD2. In those cultures which had been exposed to PGD2 virtually no thymidine incorporation was seen after 24 hours and as long as 72 hours. In another set of experiments, the effect of PGD 2, PGE 2, two synthetic PGD 2 analogues, with a chlorine substitution in position 9 (DACl) or with a fluoride substitution in position 9 (DAF) and a synthetic prostacyclin-analogue (Iloprost) was investigated after single and repeated addition of the compounds. A second administration after 12 hours of incubation did not result in a further decrease in 3H-thymidine incorporation like that observed during that first incubation period. In general the cells recovered after 24 hours total incubation time except those which had received PGD 2 or repeated doses of PGE 2. Only in those cells which had been treated with PGD 2, an almost complete blockade of 3H-thymidine incorporation was seen even after the single administration. Parallel evaluation of the cells by flow cytometry showed effects on cell cycle distribution at different times of the incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1978

A comparison of the inhibitory effects of taurine and GABA on identified Purkinje cells and other neurons in the cerebellar cortex of the rat.

The microiontophoretic application of taurine and GABA was studied in the cerebellar cortex of the rat. Both taurine and GABA produced a dose-dependent depression of spike frequency of cerebellar neurons. GABA (2-42 nA, mean 27 nA) induced an inhibition of spike discharge on all 138 cells tested, including 29 Purkinje cells. Taurine (60-200 nA, mean 108 nA) induced an inhibition of spike discharge on 93 of the 106 cerebellar neurons tested, including inhibition on 22 of 25 Purkinje cells. Iontophoretic application of bicuculline and picrotoxin antagonized the inhibitory effects of both GABA and taurine on Purkinje cells as well as on cerebellar neurons in general. Strychnine did not antagonize the inhibition of either GABA or taurine. Simultaneous application of taurine and GABA produced a synergistic inhibitory effect on the firing rate of Purkinje cells. Taurine, in contrast to GABA, appeared to be more depressant when applied in the Purkinje cell dendritic zone than when applied near the soma. The data are discussed in terms of taurine functioning as a neurotransmitter in the cerebellum of the rat and having receptor sites distinct from those for GABA.

Aminobutyrates↗
PubMedDate not supplied

[Recurrent pigmented villonodular synovitis (PVNS)].

AIM: The pigmented vilionodular synovitis (PVNS) is a tumour like disease of unknown origin that often shows recurrence. The pathogenesis is still unknown and therefore the question of the right therapy is not resolved. MATERIAL: With a case report of a patient with recurrence after two arthroscopic synovectomies, PVNS is discussed against the background of the clinical, histological, and radiological features. RESULTS: We performed an open synovectomy and cystic lesions in both condyles of the femur and proximal tibia were filled with homologous and autologous cancellous bone. Three months later the patient had no pain and the bone density in the former cystic lesions was appropriate. DISCUSSION: The pathogenesis is still unknown. Diagnosis often is obtained much too late due to missing specific symptoms. PVNS occurs in local forms as well as in a diffuse growth pattern. Recurrence rates of up to 78% are very high. Besides arthroscopic and open synovectomy, the treatment with radiosynoviorthesis must be considered. Depending on the growth pattern, the tumour masses, and the affected joint, the therapy has to be chosen very carefully and sometimes different forms have to be combined if a recurrence--free result is to be achieved.

Adult↗
PubMedDate not supplied

[[F-18]-fluorodeoxyglucose (FDG) positron emission tomography (PET) as a diagnostic for hip endoprosthesis loosening].

AIM: The purpose of this study was to examine the FDG-PET in respect of its diagnostic valency with regard to septic/aseptic loosening of lower limb prostheses. METHOD: 28 patients with 41 lower limb prostheses were examined by means of FDG-PET to evaluate septic/aseptic loosening of their hip prostheses. Therefore, a differentiated FDG-PET result interpretation subdivided into five categories was developed. The final diagnosis was based on operative findings with following culture and histological outcome. RESULTS: The worked-out categories showed a high agreement to the intraoperative macroscopic and histological results (n = 23 correctly positive, n = 1 false positive, n = 1 correctly negative and n = 3 false negative). CONCLUSION: With a subtly differentiated interpretation (categories I - V) of the qualitative glucose metabolism safe statements can be made regarding septic/aseptic endoprostheses loosening. This was impressively confirmed by the agreement of the FDG results with the histological results.

Aged↗
PubMedDate not supplied

[The cement-free modular revision prosthesis MRP-hip revision stem prosthesis in clinical follow-up].

INTRODUCTION: We present prospective medium-term results of the modular revision prostheses "MRP-TITANIUM". MATERIAL AND METHODS: 45 patients (n = 48 prostheses) were evaluated. The mean follow-up was 4.7 years (min.-max.: 1.0-9.0 years). Pre- and postoperatively the Harris hip score (differentiated to Paprosky I-III) was examined. 66.67 % of the cases had extensive bony defects (> or = Paprosky II b). By means of X-ray examinations, the stability of the prostheses, periprosthetic bone remodelling, the presence of radiolucent lines as well as bone defect regeneration were assessed postoperatively. RESULTS: The mean Harris hip score improved from 25.6 preoperative to 71.4 postoperative (p < or = 0.05). In 44 cases the X-ray showed stable fixation without secondary migration. In one case the stem (stand time 2.36 years) was revised due to secondary migration (> or = 5 mm). The survival rate (Kaplan-Meier) was 97 %. Bone transplantation with consecutive defect regeneration was (n = 30) complete in all cases. In six cases (12.5 %) a postoperative dislocation occurred with subsequent successful closed reposition four times (8.3 %). In two cases (4.2 %) an open reposition was done with correction of the antetorsion angle of the prostheses. CONCLUSION: The "MRP-TITANIUM modular revision prostheses" has proved to be reliable in cases of revision surgery with extensive bony defects. The failure rate was 2.1 % for 48 prospectively examined prostheses.

Aged↗
PubMedDate not supplied

[Is the implantation of titanium stems in hip prostheses really obsolete?].

AIM: Due to several bad results of studies, titanium is no longer used as an implant material in cemented total hip arthroplasty. This study attempts figure out by means of a meta-analysis if the material titanium itself was responsible for the bad results of some studies or if specific implant characteristics contributed to implant failure, independent of titanium. METHOD: Studies between 1960 and July 2002 were analysed concerning failure rates of cemented titanium total hip arthroplasties regarding their specific implant characteristics. RESULTS: Specific implant characteristics such as roughness of the surface and geometrical features led to significantly different failure rates. Stems of titanium with a dull surface and a wide proximal geometry could achieve such good results as those of the cobalt-chromium stems published in the study results of Malchau. CONCLUSION: Titanium is justified as a cementable material in total hip arthroplasty. By respecting specific implant characteristics, very good failure rates can be achieved. The high failure rates, published in several studies, are based upon implant characteristics which are not suitable for cementing techniques and not upon the implant material titanium itself.

Arthroplasty, Replacement, Hip↗