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Biomedical subjects

M Späth

Publications and source records attributed to M Späth.

At least 37 records · Page 2Linked to original sources
PubMed1998

Morphologic aspects of fibromyalgia.

The most common morphological finding in muscle biopsies in longstanding fibromyalgia is type II fiber atrophy. This can be found in many other conditions such as disuse atrophy, affections of the corticospinal tracts, steroid atrophy, and other different neuromuscular disorders. An increase in lipid droplets and a slight proliferation of mitochondria in type I muscle fibers are correlated with the duration of fibromyalgia. In some cases we could find some ragged red fibers (RRF) which histochemically show a pronounced accumulation of lipids and mitochondria and single fiber defects of cytochrome-c-oxidase. In some fibromyalgia patients with RRF, we could find deletions of the mitochondrial genoma.

Fibromyalgia↗
PubMed1996

Sjoegren's syndrome: MR imaging of the parotid gland.

To date, myoepithelial sialoadenitis (Sjoegren's syndrome) has been diagnosed with sialography and other techniques. First results of MR imaging offer new possibilities in the diagnostic imaging of this disease. Thirty-six patients with immunohistologically and serologically confirmed Sjoegren's syndrome and 25 patients suffering from other diseases, included as a control group, were examined by MR in transverse and coronal orientation. T-2-weighted sequences (TR/TE 1600/25/90) and T1-weighted sequences (TR/TE 500/25 ms) plain and after Gd-DTPA administration were obtained. In all patients the parotid gland showed characteristic internal patterns and abnormalities in gland size. There was a nonhomogeneous internal pattern with a characteristic speckled, honeycomb-like appearance visible especially on T2-weighted sequences. Enhancement with Gd-DTPA yielded no additional information. A staging system with four stages of Sjoegren's syndrome (no characteristic changes to a nodular and swollen gland) was developed. Magnetic resonance has become an important new tool in assessing parotid gland changes in patients suffering from Sjoegren's syndrome, and could well replace the more invasive and unpleasant diagnostic methods in the near future.

Acute Disease↗
PubMed1996

Arginine vasopressin and oxytocin increase intracellular calcium and cAMP in human glomerular epithelial cells in culture.

The signal transduction linkages of arginine vasopressin (AVP) and oxytocin receptors were investigated in human glomerular epithelial cells (GEC) in culture. AVP (ED50, 10(-7) mol/l) and oxytocin (ED50, 3 x 10(-8) mol/l) induced a rapid, transient and dose-dependent increase in [Ca2+]i as detected by fura-2 microfluorimetry. The baseline of [Ca2+]i in human GEC was 109 +/- 2.8 nmol/l (n = 60). The V1a receptor antagonist [d(CH2)5(1), Tyr(Me)2, Arg8]-vasopressin inhibited the AVP-(IC50, 5 x 10(-9) mol/l) and oxytocin-induced (IC50, 3 x 10(-8) mol/l) increase in [Ca2+]i in a dose-dependent manner. Both, AVP and oxytocin caused accumulation of cAMP. The AVP-stimulated cAMP increase was blocked by pretreatment of human GEC with the V1a receptor antagonist (10(-7) mol/l), whereas the oxytocin-induced cAMP accumulation remained uninfluenced. In conclusion the present results indicate that: (1) V1a receptor activation, AVP and oxytocin induce a transient elevation in [Ca2+]i in human GEC; (2) AVP and oxytocin cause cAMP accumulation; (3) the AVP-induced cAMP accumulation is inhibited by a V1a receptor antagonist, whereas (4) the oxytocin response showed no effect. In addition, a different receptor might be possible, at least in oxytocin-induced-cAMP accumulation.

Antidiuretic Hormone Receptor Antagonists↗
PubMed1995

[T-cell lymphoma under immunosuppressive treatment in minimal change glomerulopathy with nephrotic syndrome].

HISTORY AND CLINICAL FINDINGS: A 43-year-old woman was admitted for treatment of a nephrotic syndrome with increasing oedema, ascites, dyspnoea and nausea during the preceding 2 weeks. INVESTIGATIONS: There was a proteinuria of 25 g daily. Renal biopsy (seven glomeruli) showed a minimal-change glomerulopathy. TREATMENT AND COURSE: Prednisone administration (1 mg/kg daily) achieved complete remission. In the course of this treatment the patient contracted listeriosis with encephalitis, which quickly responded to ampicillin and netilmicin. When the glucocorticoid dosage was reduced or the drug discontinued, the nephrotic syndrome recurred. Cyclosporin treatment was begun (5 mg/kg daily) and quickly led to another remission. 4 weeks after start of the treatment a reddish-blue nodule, about 2 cm in diameter, was noted on the right upper arm. Histologically it showed cutaneous infiltration of a medium-sized T-cell lymphoma. Other efflorescences were found on the trunk and the limbs. Cyclosporin treatment was at once discontinued and the cutaneous changes gradually regressed. There were no other manifestations of a lymphoma. A further recurrence of the nephrotic syndrome responded well to a short course of chlorambucil (cumulative dose 420 mg) and of prednisone with slow dose reduction. There has been no recurrence in the last year.

Adult↗
PubMed1995

Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by endothelin in human glomerular epithelial cells.

The regulation of the inositide signalling pathway and [Ca2+]i by endothelin (ET) peptides was investigated in human glomerular epithelial cells in culture. Endothelin-1 and -2 induced an accumulation of inositol phosphates in a time- and dose-dependent manner. The baseline of [Ca2+]i in glomerular epithelial cells was 109 +/- 2.8 nmol/l, n = 60. Endothelin-1 (ED50: approx. 3 x 10(-9) mol/l) caused a rapid and transient rise in [Ca2+]i as detected by fura-2 microfluorimetry studies. The endothelin-1-induced inositol phosphate accumulation was inhibited by the selective ETA receptor antagonist BQ123. Endothelin-3 and BQ3020, a selective ETB receptor agonist, showed no effect. The results suggest an ETA-mediated pathway. This study demonstrates an ETA-mediated transmembrane signalling via phospholipase C with consecutive elevation of inositol phosphates and intracellular calcium. Since endothelin peptides contribute to both normal renal function and renal dysfunction, this study adds further knowledge on glomerular cell regulation.

Calcium↗
PubMed1994

Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease.

Impaired platelet function and a bleeding tendency are well-recognized complications of chronic renal failure. Because the fibrinogen receptor GPIIb-IIIa plays a central role in platelet aggregation and adhesion to the subendothelium, it was reasoned that a defect in this receptor may underlie the impaired platelet function in uremia. To test this hypothesis, the function of this receptor in the platelets of 11 uremic patients was studied. Aggregation studies were performed with flow cytometric techniques with anti-GPIIb-IIIa conformation-specific monoclonal antibodies (mAb) (anti-LIBS1 and anti-PMI-1). Antifibrinogen and antithrombospondin mAb were used to characterize fibrinogen binding to GPIIb-IIIa and the release of alpha-granules, respectively. Platelets from patients with chronic renal failure showed significantly decreased binding of conformation-dependent anti-LIBS1 mAb after ADP, phorbol myristate acetate, or RGD-peptide stimulation compared with normal controls, suggesting a defect related to the ability of the fibrinogen receptor to undergo a conformational change. Moreover, antifibrinogen and antithrombospondin binding to activated platelets were reduced in uremic patients, implying impairment of both ligand-binding and alpha-granule release. Hemodialysis partially restored GPIIb-IIIa function, which may account for the observed effects of this therapy in restoring platelet aggregation. These findings indicate that platelets of patients with chronic renal failure reveal an aggregation defect at least partially due to an intrinsic GPIIb-IIIa dysfunction and the presence of a putative uremic toxin that inhibits fibrinogen binding to GPIIb-IIIa.

Adenosine Diphosphate↗
PubMed1993

Effect of bradykinin and histamine on the membrane voltage, ion conductances and ion channels of human glomerular epithelial cells (hGEC) in culture.

The effects of bradykinin (BK) and histamine (Hist) on the membrane voltage (Vm), ion conductances and ion channels of cultured human glomerular epithelial cells (hGEC) were examined with the nystatin patch clamp technique. Cells were studied between passage 3 and 20 in a bath rinsed with Ringer-like solution at 37 degrees C. The mean value of Vm was -41 +/- 0.5 mV (n = 189). BK (10(-6) mol/l, n = 29) and Hist (10(-5) mol/l, n = 55) induced a rapid transient hyperpolarization by 15 +/- 1 mV and 18 +/- 1 mV, respectively. The hyperpolarization was followed by a long lasting depolarization by 6 +/- 1 mV (BK 10(-6) mol/l) and 7 +/- 1 mV (Hist 10(-5) mol/l). The ED50 was about 5 x 10(-8) mol/l for BK and 5 x 10(-7) mol/l for Hist. In the presence of both agonists, increases of outward and inward currents were observed. A change in the extracellular K+ concentration from 3.6 to 30 mmol/l depolarized Vm by 8 +/- 1 mV and completely inhibited the hyperpolarizing effect of both agents (n = 11). Reduction of extracellular Cl- concentration from 145 to 30 mmol/l led to a depolarization by 2 +/- 1 mV (n = 25). In 30 mmol/l Cl- the depolarizations induced by BK (10(-7) mol/l) and Hist (10(-6) mol/l) were augmented to 9 +/- 2 mV (n = 14) and to 10 +/- 2 mV (n = 11), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Bradykinin↗
PubMed1992

Effect of nucleotides on the cytosolic free calcium activity and inositol phosphate formation in human glomerular epithelial cells.

1. Glomerular epithelial cells (GEC) were cultured from human kidneys and immunologically characterized. 2. The effect of extracellular nucleotides on the cytosolic free calcium activity [Ca2+]i was investigated with the fura-2 microfluorescence method. Extracellular UTP, UDP, UMP, ATP, adenosine 5'-O-(3-thio)-trisphosphate (ATP-gamma-S), inosine-triphosphate (ITP), guanyltriphosphate (GTP), 2-methylthio-ATP, AMP, alpha,beta-methylene-ATP and adenosine led to a rapid, transient, concentration-dependent increase of [Ca2+]i, followed by a plateau above the baseline level. 3. In a calcium-free extracellular solution, the rapid increase of [Ca2+]i was still present, whereas the plateau level was abolished. 4. ATP and UTP (ED50 both: 10(-5) M) stimulated inositol trisphosphate (InsP3) formation in GEC. 5. The order of potency for the purine nucleotides in stimulating InsP3 formation was ATP = ATP-gamma-S greater than ADP greater than 2-methylthio-ATP greater than AMP = a,beta methylene-ATP = adenosine. 6. The increase of InsP3 induced by ATP (10(-5) M) could be inhibited by the P2 receptor blocker suramin (greater than 10(-4) M). Reactive blue 2 exhibited a weak stimulating effect on the InsP3 formation and only a weak inhibitory effect at a concentration of 10(-3) M was observed. 7. Protein kinase C activation by preincubation of GEC with phorbol 12-myristate 13-acetate (PMA, 100 ng ml-1, 15 min) abolished the effect of ATP (10(-5) M) on InsP3 formation. Downregulation of protein kinase C by long term incubation (18 h) with PMA had no significant effect on the phosphoinositol turnover induced by ATP.8. The results indicate that an increase of [Ca2+]i and inositol phosphate breakdown can be mediated via activation of a P2 receptor in human GEC.

Adenosine Triphosphate↗
PubMed1991

Potassium conductance of smooth muscle cells from rabbit aorta in primary culture.

Vascular smooth muscle cells were obtained from rabbit aorta and were studied in primary culture on days 1-7 after seeding with electrophysiological techniques. In impalement experiments a mean membrane potential difference (PD) of -50 +/- 0.3 mV (n = 387) was obtained with Ringer-type solution in the bath. PD was depolarized by 6 +/- 0.3 mV (n = 45) and 16 +/- 2 mV (n = 5) when the bath K+ concentration was increased from the control value of 3.6 mmol/l to 13.6 and 23.6 mmol/l, respectively. Ba2+ (0.1-1 mmol/l) depolarized PD. Tetraethylammonium (TEA, 10 mmol/l) depolarized PD only slightly but significantly. Verapamil (0.1 mmol/l) and charybdotoxin (10 nmol/l) had no effect on PD. The conductance properties of these cells were further examined with the patch-clamp technique. K+ channels were spontaneously present in cell-attached patches. When the pipette was filled with 145 mmol/l KCl, a mean conductance (gK) of 209.6 +/- 4.6 mV (n = 17) was read from the current/voltage curves at a clamp voltage (Vc) of 0 mV. After excision K+ channels were found in 129 patches with inside-out and in 50 with outside-out configuration. With KCl on one and NaCl on the other side the mean gK at a Vc of 0 mV was 134.6 +/- 3.9 pS (n = 179). The mean permeability was 0.89 +/- 0.03 x 10(-12) cm3/s. With symmetrical KCl solution the mean gK was 227 +/- 6 pS (n = 17). The conductance sequence was gK much greater than gRb = gCs = gNa = 0. TEA blocked dose-dependently only from the outside (1-10 mmol/l). Lidocaine (5 mmol/l) quinidine (0.01-1 mmol/l) and quinine (0.01-1 mmol/l) blocked from both sides. Charybdotoxin (0.5-5 nmol/l) blocked only from the extracellular side. Ba2+ blocked from the cytosolic side and the inhibition was increased by depolarization and reduced by hyperpolarization. At a Vc of 0 mV a half-maximal inhibition (IC50) of 2 mumol/l was obtained. Verapamil and diltiazem blocked from both sides, verapamil with an IC50 of 2 mumol/l and diltiazem with an IC50 of 10 mumol/l. The open probability of this channel was increased by CA2+ on the cytosolic side at activities greater than 0.1 mumol/l. Half-maximal activation occurred at Ca2+ activities exceeding 1 mumol/l. The present data indicate that the vascular smooth muscle cells of rabbit aorta in primary culture possess a K+ conductance. In excised patches only a maxi K+ channel was detected. This channel has properties different from the macroscopic K+ conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effect of depolarizing and hyperpolarizing agents on the membrane potential difference of primary cultures of rabbit aorta vascular smooth muscle cells.

Vascular smooth muscle cells of rabbit aorta were enzymatically dispersed, kept in primary culture, and studied between days 1 and 7 in a bath rinsed with Ringer-like solution at 37 degrees C. The electrical membrane potential difference (PD) was measured with microelectrodes. The mean value of PD was -50 +/- 0.4 mV (n = 53). Cromakalim (BRL 34915), 1 mumol/l and 10 mumol/l, hyperpolarized the membrane potential by 9 +/- 1 mV (n = 11) and 15 +/- 1 mV (n = 53) respectively. Glibenclamide (10 mumol/l) abolished the hyperpolarizing effect of chromakalim (n = 6). Simultaneous addition of cromakalim and glibenclamide (both 10 mumol/l, n = 11) and glibenclamide itself (10 mumol/l, n = 7) had no effect on PD. In patch-clamp experiments in outside-out-oriented Ca(2+)-sensitive K+ channels, cromakalim increased the open probability (Po) only slightly and only with a cytosolic Ca2+ activity of 1 mumol/l. In all other series cromakalim had no effect on the Po of these channels. Forskolin (10 mumol/l) hyperpolarized PD by 6 +/- 1 mV (n = 13). The nucleotides UTP, ATP and ITP (10 mumol/l) depolarized PD by 12 +/- 1 mV (n = 7), 8 +/- 1 mV (n = 65) and 5 +/- 1 mV (n = 6) respectively. GTP, [alpha, beta-methylene]ATP and adenosine had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Characterization of multiple forms of phosphoinositide-specific phospholipase C from bovine aorta.

Three forms (I, II and III) of phospholipase C were separated from the cytosol of bovine aorta by chromatography on Blue Sepharose. All three forms showed an increase of enzyme activity when free Ca2+ in the assay was raised between 40 microM and 9 mM. The pH optimum was in the range of 6.0 to 6.5 for each subtype. Marked differences in thermostability were found when the three enzyme forms were pre-incubated at 50 degrees C prior to the assay. All three forms were able to hydrolyse phosphatidylinositol as well as phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate. In contrast, when phosphatidylcholine was used as substrate, no enzyme activity was observed. Spermine and spermidine, but not putrescine, were able to stimulate form I and III; neomycin sulphate inhibited all three subtypes.

Animals↗
PubMed1991

Magnetic resonance imaging of the parotid gland in patients with Sjögren's syndrome.

To detect structure and size abnormalities, magnetic resonance imaging (MRI) of the parotid gland was performed on 36 patients with sicca complaints. Twenty-four patients had primary Sjögren's syndrome (SS) without rheumatoid arthritis (RA) or connective tissue disease; 6 had secondary SS associated with RA, whereas in another 6 cases the related disease could not be classified. Characteristic gland size and structural abnormalities were identified in patients with SS and various stages could be established, compared to patients with other parotid gland disorders, as well as healthy persons. MRI provides an accurate noninvasive technique for assessment of xerostomia in patients with SS.

Arthritis, Rheumatoid↗
PubMed1990

[Immuno-diagnostic findings in "secondary" Sjögren syndrome in chronic polyarthritis].

In order to characterize typical findings in patients (pts.) with secondary Sjögren's Syndrome (SS) associated with rheumatoid arthritis (RA), 173 patients with RA were studied. Pathological screening-test results (Schirmer- and Saxon-test) were followed by ENT- and ophthalmological investigations and examinations in the field of internal medicine. Secondary SS associated with RA was diagnosed in 34 pts. (20%). Immuno-serological SS-A and/or SS-B-antibodies were found in 11 (32%) of 34 patients. 9 pts. (27%) had antinuclear antibodies. Abnormal titers of circulating immune complexes were present in the sera of 24 pts. (71%), salivary gland-antibodies in 3 pts. (9%). In 16 of 34 pts. (47%) minor salivary gland biopsy was performed. Lympho-plasma cell sialadenitis could be verified in all pts. Immuno-histological reactions to anti-IgG and/or anti-IgM and/or anti-IgA were detected in 10 (62%) of 16 pts. We could not find a single criterion to ascertain the diagnosis SS which still has to be made by considering all clinical and serological findings. Immunological findings may provide helpful and interesting diagnostic aspects which by long term observation may even gain importance; however, no differential therapeutic consequences can be seen at the moment.

Antibodies, Antinuclear↗
PubMed1990

Parotid gland: plain and gadolinium-enhanced MR imaging.

The purpose of this study was to show the typical appearance of lesions of the parotid gland with plain MR imaging and MR imaging enhanced with gadopentetate dimeglumine. Seventeen patients with inflammatory changes and 43 with benign and malignant tumors were studied. The examinations were carried out with plain T1-weighted sequences with a repetition time (TR) of 500 msec and an echo time (TE) of 25 msec (TR/TE = 500/25), T2-weighted sequences (1,600/90), and gadolinium-enhanced T1-weighted sequences in axial, coronal, and sagittal orientations. For identifying normal anatomic structures such as the facial nerve and the main duct, the administration of gadopentetate dimeglumine was helpful. In inflammatory changes, gadolinium-enhanced images showed no diagnostic advantages. Gadopentetate dimeglumine proved helpful in delineating tumorous lesions and in differentiating benign and malignant lesions. However, an exact differentiation of the different histologic types was not possible. Post-operative fibrosis could be differentiated from recurrent tumors after administration of gadolinium. If a question regarding infiltration or definition of the boundaries of a lesion cannot be answered with non-enhanced MR imaging, gadopentetate dimeglumine administration is advised. However, for routine imaging of the parotid gland, its use is not recommended.

Contrast Media↗
PubMed1989

[Magnetic resonance tomography of the parotid gland: plain diagnosis and Gd-DTPA].

Pathological lesions of the parotid gland were examined comparatively with different examination sequences both plain and with the contrast medium Gd-DTPA. There were 36 benign lesions (parotitis, Sjögren's syndrome, adenoma, etc.) and 24 malignant tumours (squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma etc.) Examinations were carried out at 1.0 T with long and short spin echo sequences in transverse and frontal layer orientation before and after application of Gd-DTPA as contrast medium. In the patients suffering from parotitis the best results were obtained with plain T1 and T2 sequences; the contrast medium Gd-DTPA remained without superior diagnostic relevance. However, in Sjögren's syndrome (myoepithelial sialadenitis) administration of the contrast medium always yielded a characteristic honeycomblike pattern. In benign and malignant space-occupying growths MRI supplied additional diagnostic information with Gd-DTPA in respect of defining the tumour borderlines and paths of infiltration. MRI is now a significant diagnostic tool in inflammatory and tumorous lesions of the parotid gland.

Adenocarcinoma↗
PubMed1987

Influence of symptom-limited stress on blood lactate behaviour in coronary heart disease (CHD) patients.

In order to document the possible influence of stress limiting factors (STLF: chest pain, ST-segment depression) on exercise-induced blood lactate increase in CHD patients (post myocardial infarction) 88 males were examined in a stepwise bicycle stress test. Blood lactate samples were drawn at the end of each stress step. The patients were divided into 2 groups without (n = 45) and with (n = 43) STLF, higher blood lactate concentrations, however, were only observed in relation to the exercise intensity reached at the end of the stress test. Neither the symptom chest pain nor the degree of ST-depression showed a significant influence on the physical performance capacity and the lactate concentration at the anaerobic threshold. Nevertheless, a physical performance capacity above 1 W/kg seems to be necessary to reach the anaerobic threshold level. When the lactate measurement is used in CHD patients, the influence of age on the maximum lactate concentrations must be considered.

Aged↗