PubMed Health⌕ Search

Biomedical subjects

M Seyfarth

Publications and source records attributed to M Seyfarth.

At least 55 records · Page 3Linked to original sources
PubMed1997

High-resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB1*0301, DQB1*02 haplotypes.

Selective immunoglobulin A (IgA) deficiency, the most common form of primary immunodeficiency, is related to the HLA genes. Previous studies demonstrated associations with particular HLA-DR-DQ haplotypes and a neutral amino acid at position 57 of the DQbeta chain was implicated in the susceptibility to selective IgA deficiency. In this study we reanalyzed the reported findings by high-resolution DNA typing of the loci DRB1, DQB1 and DQA1. We compared the typing results of 74 IgA-deficient individuals, detected by screening of blood donors, with those taken from 111 healthy controls. Results confirmed a strong positive association with DRB1*0301, DQB1*02 and a negative association with DRB1*1501, DQB1*0602. Considering the molecular interactions between HLA class II alleles and the peptides bound we conclude that the amino acid at position 57 of the DQbeta chain may contribute to the susceptibility to selective IgA deficiency, but not determine it. An extended statistical analysis strengthened the hypothesis that selective IgA deficiency might be communicated by the distinct haplotype DRB1*0301, DQB1*02.

DNA↗
PubMed1997

Polymorphisms in the tumor necrosis factor genes in Wegener's granulomatosis.

Two known di-allelic polymorphisms in the tumor necrosis factor (TNF) genes were investigated in 35 patients suffering from Wegener's granulomatosis (WG) in comparison to 111 healthy controls. The first polymorphism lay in the promotor region of the TNF-alpha gene at position -308, the second in the first intron of the TNF-beta gene. For both polymorphisms we could not find any statistically significant differences in allele frequencies between patients and healthy individuals. In the patient group the TNF 2/2 phenotype was slightly elevated, however (WG 5.7% vs. normal 1.8%). Investigating the clinical course of the disease according to TNF polymorphisms, TNF 1/1 patients were found to have a higher mean disease extension index (DEI) than TNF 1/2 individuals (TNF 1/1 10.5 vs. TNF 1/2 9.4).

Granulomatosis with Polyangiitis↗
PubMed1996

Nonexocytotic noradrenaline release induced by pharmacological agents or anoxia in human cardiac tissue.

In acute myocardial ischemia, noradrenaline is released locally from sympathetic varicosities by a Ca(2+)-independent nonexocytotic release mechanism that is effectively suppressed by inhibitors of the neuronal noradrenaline carrier (uptake1). The purpose of the present study was to elucidate the significance of free axoplasmic amine concentration and disturbed neuronal sodium homeostasis for nonexocytotic noradrenaline release in the human heart by comparing the release induced by anoxia with that induced by reserpine, tyramine, or veratridine. The overflow of endogenous noradrenaline and dihydroxyphenylethyleneglycol was assessed in human atrial tissue incubated in calcium-free Krebs-Henseleit-solution to prevent interferences by exocytotic release. The overflow of dihydroxyphenylethyleneglycol served as indicator of the free axoplasmic noradrenaline concentration. When vesicular uptake was blocked by the reserpine-like agent Ro 4-1284, high dihydroxyphenylethyleneglycol overflow was observed without concomitant noradrenaline overflow. If, however, Ro 4-1284 was combined with sodium pump inhibition (by omission of extracellular potassium) or with alteration of the transmembrane sodium gradient (by lowering the extracellular sodium concentration), both dihydroxyphenylethyleneglycol and noradrenaline were released. The indirectly acting sympathomimetic tyramine induced a marked increase in noradrenaline overflow which was accompanied by overflow of high amounts of dihydroxyphenylethyleneglycol, indicating interference of the drug with both vesicular catecholamine transport and amine transport via uptake1. Likewise, veratridine induced an overflow of noradrenaline (which was prevented by blockade of uptake1) and dihydroxyphenylethyleneglycol indicating a reserpine-like action of the drug. A disturbed energy status of the sympathetic neuron induced by cyanide intoxication or anoxia caused noradrenaline overflow which was suppressed by uptake1 blockade. Blockade of sodium channels by tetrodotoxin effectively reduced noradrenaline overflow during cyanide intoxication but not during anoxia. Anoxia-induced noradrenaline release, however, was markedly suppressed by inhibition of Na+/H+ exchange with ethylisopropylamiloride, indicating the Na+/H+ exchange as the predominant pathway for sodium entry into the sympathetic neuron during anoxia. The results demonstrate that disturbed neuronal sodium homoeostasis and impaired vesicular storage function are critical conditions, causing nonexocytotic noradrenaline release in anoxic human cardiac tissue.

Cell Membrane↗
PubMed1996

Differential presynaptic modulation of noradrenaline release in human atrial tissue in normoxia and anoxia.

1. Presynaptic modulation of noradrenaline release in human atrial tissue specimens was investigated under normoxic and anoxic conditions. 2. Noradrenaline release was induced by electrical stimulation and release during experimental intervention (S2) was compared with release during a preceding control stimulation (S1). The results were expressed as the geometric means and 95% confidence intervals of the S2/S1 ratio. 3. The alpha 2-adrenoceptor agonist, UK 14304 (0.1 mumol-1) significantly inhibited noradrenaline release, resulting in a S2/S1 ratio of 0.49 (0.40-0.59), and the a 2-adrenoceptor antagonist, yohimbine (1 mumol l-1) increased noradrenaline release (S2/S1 1.83 [1.43-2.35]) during normoxia. Both compounds were ineffective during anoxia. 4. Adenosine (30 mumol-1) inhibited noradrenaline release with a S2/S1 ratio of 0.54 (0.42-0.66). The adenosine antagonist, 8-phenyltheophylline, alone had no effect during normoxia. During anoxia, neither adenosine nor 8-phenyltheophylline altered noradrenaline release. 5. The beta 2-adrenoceptor agonist, terbutaline (1 mumol l-1) increased (1.53 [1.14-2.01]) and the beta-adrenoceptor antagonist, pindolol (1 mumol l-1) suppressed noradrenaline release (0.62 [0.49-0.79]) under normoxic conditions. During anoxia, pindolol significantly inhibited noradrenaline release with a S2/S1 ratio of 0.66 (0.51-0.85), whereas terbutaline did not influence noradrenaline release. 6. Angiotensin II (0.1 mumol l-1 enhanced noradrenaline release resulting in a S2/S1 ratio of 1.44 (1.34-1.54), while the angiotensin II antagonist, losartan (1 mumol l-1) had no effect on noradrenaline release during normoxia. Conversely, angiotensin II did not increase noradrenaline release and losartan significantly inhibited noradrenaline release to a S2/S1 ratio of 0.60 (0.46-0.77) during anoxia. 7. In conclusion, human cardiac tissue possesses presynaptic inhibitory alpha 2-adrenoceptors and adenosine receptors, as well as facilitatory beta 2-adrenoceptors and angiotensin II receptors regulating noradrenaline release under normoxic conditions. During anoxia the responses to alpha 2-adrenoceptors and adenosine receptor stimulation are lost, whereas facilitatory responses to beta 2-adrenoceptors and adenosine II receptor stimulation are maintained and these receptors appear to be maximally stimulated. This differential presynaptic modulation in anoxia may contribute to enhanced sympathetic activity in ischaemia.

Adenosine↗
PubMed1996

Transient ischemia reduces norepinephrine release during sustained ischemia. Neural preconditioning in isolated rat heart.

Endogenous catecholamine release may play a role in ischemic preconditioning either as a trigger or as a target within the process of myocardial preconditioning. Therefore, we investigated the effect of transient ischemia (TI) on norepinephrine release during sustained ischemia in isolated rat hearts. TI was induced by multiple cycles of global ischemia followed by reperfusion with a duration of 5 minutes each, comparable to ischemic preconditioning protocols. After TI, norepinephrine release was evoked by either sustained global ischemia, anoxia, cyanide intoxication, tyramine, or electrical stimulation. During TI, no washout of norepinephrine was observed, and tissue concentrations of norepinephrine were not changed. TI, however, reduced norepinephrine overflow after 20 minutes of sustained ischemia from 239 +/- 26 pmol/g (control) to 79+/-8 pmol/g (67% reduction, P <.01 ). A similar reduction of ischemia-induced norepinephrine release from 192 +/- 22 pmol/g (control) to 90 +/- 15 pmol/g was observed when hearts underwent transient anoxia without glucose (P < .05). When reperfusion between TI and sustained ischemia was prolonged from 5 to 90 minutes, the inhibitory effect of TI on norepinephrine release was gradually lost. Susceptibility to TI was a unique feature of norepinephrine release induced by sustained ischemia, since release of norepinephrine evoked by anoxia, cyanide intoxication, tyramine, or electrical stimulation remained unaffected by TI. We propose a protective effect of TI on neural tissue, which may reduce norepinephrine-induced damage during prolonged myocardial ischemia.

Animals↗
PubMed1995

Two different mechanisms of noradrenaline release during normoxia and simulated ischemia in human cardiac tissue.

Species-related differences in the mechanisms of noradrenaline release during normoxia and myocardial ischemia emphasize the need for studies on human hearts. Therefore, the mechanisms of noradrenaline release were investigated during normoxia and energy depletion in incubated human atrial tissue and compared to the release characteristics in normoxic and ischemic rat heart. Potential differences of atrial versus ventricular myocardium were assessed by comparing catecholamine release during electrical stimulation and ischemia in isolated rat atrium with release characteristics in the intact perfused heart. The overflow of endogenous noradrenaline and its deaminated metabolite dihydroxyphenylethyleneglycol (DOPEG) were determined by high pressure liquid chromatography and electrochemical detection. During normoxia noradrenaline release was evoked by electrical field stimulation. Stimulation-induced noradrenaline release depended on the extracellular calcium concentration in both species and was almost completely suppressed under calcium-free conditions. The release was significantly inhibited by neuronal (N-type) calcium channel blockers such as omega-conotoxin (100 nmol/l) and cadmium chloride (100 mumol/l), indicating a predominant role of N-type calcium channels in exocytotic noradrenaline release from sympathetic neurons in human and rat heart. Desipramine (100 nmol/l) enhanced the overflow of noradrenaline evoked by electrical stimulation in both species by blocking neuronal catecholamine uptake (uptake1). Myocardial ischemia was caused by interruption of perfusion flow in rat heart and simulated by anoxic and glucose-free incubation in human and rat atrial tissue. Ischemia- and anoxia-induced noradrenaline release in rat heart and human atrial tissue was unaffected by varying extracellular calcium concentrations and occurred even after omission of calcium and addition of EGTA (1 mmol/l). In both species neither omega-conotoxin (100 nmol/l) nor cadmium chloride (100 mumol/l) affected ischemia-induced noradrenaline overflow in both rat heart and atrium as well as in human atrium. In human and rat atrial tissue, blockade of energy metabolism in the presence of oxygen (cyanide model) resulted in a desipramine-sensitive release of noradrenaline, which was accompanied by DOPEG overflow, indicating increased axoplasmic noradrenaline concentration. The data imply a dual mechanism of noradrenaline release in the human heart. During normoxia noradrenaline release is modulated by neuronal calcium influx indicating exocytotic release. Ischemia-induced noradrenaline release, however, is independent of calcium and inhibited by uptake1 blockade suggesting nonexocytotic release mechanism. The characteristics of noradrenaline release in human atrial tissue provide evidence for carrier-mediated release of noradrenaline from sympathetic neurons operative in the ischemic human myocardium.

Adrenergic Uptake Inhibitors↗
PubMed1994

[Analysis of Candida-specific antibodies in saliva].

We developed an enzyme immunoassay for the estimation of candida-specific IgA antibodies in saliva. In patients with stomatitis prothetica (n = 46) we found a higher concentration (p < 0.05) before therapy in comparison to normal controls.

Antibodies, Fungal↗
PubMed1994

[Relationship between secretory IgA in pancreatic secretions, in pancreatic tissue, and in the serum of patients with chronic pancreatitis].

In five patients with chronic pancreatitis we found secretory IgA (sIgA) in the pancreatic juice. In four control persons this was seen only in one case. In pancreatic tissue of three patients with chronic pancreatitis we detected both, IgA and secretory component by immunohistology. We suggest that sIgA in the pancreatic juice was partly produced in the pancreas.

Chronic Disease↗
PubMed1994

[HLA and selective IgA deficiency].

A selective deficiency of IgA is developed significantly (p < 0.05) more frequently by HLA-A2-negative than by HLA-A2-positive healthy persons. The frequent combination of A1/A3 is absent. The incidence of HLA-B8-positive persons is increased (p < 0.01). A selective disadvantage is discussed.

Gene Frequency↗
PubMed1993

Effect of myocardial ischemia on stimulation-evoked noradrenaline release. Modulated neurotransmission in rat, guinea pig, and human cardiac tissue.

The effect of myocardial ischemia and its major metabolic changes, such as anoxia, acidosis, and hyperkalemia, on exocytotic noradrenaline release was investigated in rat, guinea pig, and human cardiac tissue. Noradrenaline release was evoked by electrical field stimulation, and the effect of each experimental intervention on stimulation-evoked noradrenaline release (S2) was intraindividually compared with the release induced by a control stimulation (S1). In perfused hearts, 10 minutes of global ischemia caused a reduction of noradrenaline overflow in rat hearts (mean S2/S1, 0.31), whereas the overflow was increased in guinea pig hearts (S2/S1, 1.89). This species-dependent effect may be caused by quantitatively different responses to facilitating and suppressing factors of noradrenaline release in both species. Anoxia and substrate-free perfusion increased noradrenaline overflow in guinea pig hearts (S2/S1, 2.40) but had no significant effect in rat hearts (S2/S1, 0.75). Acidosis (pH 6.0) resulted in a suppression of noradrenaline release in rat hearts (S2/S1, 0.16), whereas it had only a minor inhibiting effect in guinea pig hearts (S2/S1, 0.67). Hyperkalemia had a comparable effect in both species (S2/S1 at 15 mmol/L K+, 1.17 in rat and 1.14 in guinea pig; and S2/S1 at 20 mmol/L K+, 0.64 in rat and 0.41 in guinea pig). To obtain results regarding the modulation of noradrenaline release in human myocardium, human atrial tissue was incubated, and the effect of anoxia, acidosis, and hyperkalemia on stimulation-evoked noradrenaline release was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1993

[New intervention procedures: lasers, atherectomy, stents].

New coronary devices--atherectomy, laser angioplasty, and stents--have been designed to overcome main limitations of conventional balloon angioplasty (PTCA). So far, none of the new devices has clearly demonstrated a general superiority regarding acute complications. Late outcome and restenosis are not affected by the type of intervention, but mainly determined by the primary success, i.e. the safely obtained postprocedure lumen diameter. Although the new coronary devices may not replace conventional PTCA in "standard" situations, there are specific indications (venous bypass grafts, aorto-ostial lesions, complex calcified lesions) for atherectomy, laser angioplasty, and stents with better acute results compared to PTCA. Since the best post-procedural result determines the extent of restenosis, it is crucial to select the appropriate device for special lesions or acute complications.

Angioplasty, Balloon, Coronary↗
PubMed1993

[Follow-up study of the development of autoantibodies in patients with chronic inflammatory bowel disease under anti-CD4 therapy].

7 of 22 patients with chronic inflammatory bowel diseases (Crohn's disease, ulcerative colitis) were treated with an anti-CD4-mAb. In the immunological monitoring the amounts of autoantibodies to pancreatic acini cells, to intestinal goblet cells, to granulocytes with perinuclear fluorescence pattern were examined and human anti-mouse-antibodies were measured. After anti-CD4 therapy the production of autoantibodies was widely unchanged. Therefore its use as parameter in the follow-up is restricted.

Antibodies, Monoclonal↗
PubMed1992

Physiological concentrations of ANP exert a dual regulatory influence on renin release in conscious dogs.

The influence of physiological increments in circulating atrial natriuretic peptide (ANP) on renin release was determined in conscious dogs. Renin stimulus-response curves (RSRCs) were obtained by controlled reductions of renal perfusion pressure (RPP) under control conditions and during intrarenal or intravenous ANP infusions. Under all experimental conditions, the RSRCs were characterized by a plateau, a threshold pressure (Pth), and a steep slope below Pth. Intrarenal ANP infusion (0.9 ng.kg-1.min-1), which induced a calculated threefold elevation of renal arterial ANP concentration (but did not change systemic arterial ANP levels), increased the slope of the RSRC by 81% (P less than 0.05) with no effect on Pth. A quantitatively similar effect on the slope of the RSRC (+90%; P less than 0.05) was observed when systemic ANP levels were raised (from 37 +/- 2 to 71 +/- 9 pg/ml; P less than 0.05) by intravenous infusions (3.6 ng.kg-1.min-1). In addition, however, intravenously infused ANP reduced Pth from 91 to 85 mmHg (P less than 0.05), which caused a complete suppression of the renin response to a reduction of RPP down to 85 mmHg. These findings indicate that ANP can inhibit renin release at physiological plasma concentrations by shifting the RSRC to a lower pressure level; this shift is mediated by a modulation of extrarenal renin control mechanisms. The direct effect of ANP on renin release is one of stimulation.

Animals↗
PubMed1991

Serum concentration of secretory IgA during pregnancy and in gynaecological diseases affecting glands and mucosas.

Secretory IgA (S-IgA) was measured in serum samples from pregnant women by means of radial immunodiffusion according to Mancini with an antiserum against the secretory component and an S-IgA standard. The results neglect the differentiation in SC, S-IgA, and S-IgM. The study includes S-IgA serum levels during pregnancy and post partum as well as in patients with cervical carcinoma and inflammation of the genital tract. The S-IgA serum levels of pregnant women (2nd and 3rd trimester) and after delivery were increased significantly in comparison to nonpregnant women (p less than 0.01). The S-IgA levels in genital inflammation diseases and cervical carcinoma were only sometimes elevated. Pregnant women, 1st trimester: means = 40.0 mg/l (s = 12.2); pregnant women, 2nd trimester: means = 60.13 mg/l (s = 18.9); pregnant women, 3 rd trimester: means = 73.5 mg/l (s = 17.4); post partum: means = 77.5 mg/l (s = 29.52); cervical carcinoma: means = 41.9 mg/l (s = 17.3); adnexitis: means = 46.46 mg/l (s = 16.8); controls: means = 38.61 mg/l (s = 10.5). In a second part S-IgA could be estimated in serum samples of pregnant women by means of an enzyme-linked immunosorbent assay (ELISA). The levels ranged from 7.1 mg/l to 19.3 mg/l in the 1st trimenon and from 16.8 mg/l to 82 mg/l in the 3rd trimenon (means = 11.72 mg/l; s = 4.419; n = 21 and means = 40.01 mg/l; s = 15.117; n = 60). This increasing was significant too (p less than 0.01).

Adult↗
PubMed1991

[The quantitative determination of resistance factors in the saliva of patients with very high caries involvement].

The unstimulated and stimulated whole saliva of patients with a very high caries experience were used for the determination of the flow rate, total protein, and the antibacterial proteins lysozyme, S-IgA and lactoferrin as well as the peroxidase and thiocyanate being components of the salivary peroxidase system. The concentration, the specific concentration and the secretion rate were calculated.

Adult↗
PubMed1990

[Studies on the local defense reactions of the nasal mucosa in employees in Rostock harbor exposed to large amounts of dust].

Defense mechanisms of the nasal mucosa are characterised by resistance and immunity processes. Secretory IgA seems to be very important for immune response. The aim of our work was to clarify whether the concentration of S-IgA in nasal secretion was influenced by extreme exposure of dock workers to dust. We investigated the nasal fluid of both the septum and the turbinate mucosa of 75 dock workers compared with 12 controls. A decrease of S-IgA concentration in the nasal fluid was seen after the work. This decrease differed for the various types kinds of dust and was significant (p less than 0.05) for apatite, urea and potash. A reduction of S-IgA was also seen after exposure for a longer time (several years). Dockers with repeated infections do not have decreased S-IgA values. These investigations make a contribution to the immune response in the nasal mucosa.

Dust↗