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Biomedical subjects

R Seitz

Publications and source records attributed to R Seitz.

At least 55 records · Page 3Linked to original sources
PubMed1994

Coagulation factors and markers of activation of coagulation in homocystinuria (HOCY): a study in two siblings.

Homocystinuria due to cystathionine-beta-synthase deficiency (CBS-def-HOCY) initially often present with thromboembolic events. In most cases in which coagulation factors have been analysed, a deficiency of AT-IIIc and factor VIIc has been reported, the cause of which has not been elucidated. Activation of coagulation with consumption of coagulation factors has been postulated as the mechanism. This paper reports a longitudinal study of two patients: patient 1 with thromboembolic disease and his asymptomatic sister, patient 2. Before start of therapy in patient 1, a reduction of FVIIc, other coagulation factors, and AT-IIIc was found. Markers of activation of coagulation (F1 + 2, TAT, FM, D-dimers) were elevated only in patient 1, and only at the time of thrombotic complications. In patient 2 reduced levels of FVIIc and other coagulation proteins, and a low borderline AT-IIIc level was found. Thus, in the two patients, sustained activation of coagulation can be reasonably excluded to be the cause of low levels of coagulation proteins. Vitamin therapy with 15 mg folate and 600 mg pyridoxine per day led to almost complete normalization of amino acids in urine and plasma. Thrombosis has not recurred to date. FVIIc and the other coagulation proteins and AT-IIIc increased in parallel with the biochemical remission. Direct inhibition of the activity of AT-III and coagulation factor VIII and other factors by homocysteine was attempted in vitro but could not be shown at HC concentrations known to occur in the plasma of HOCY patients. Therefore, in these patients, deficient synthesis of coagulation factors and AT-III due to a disturbance of amino acid metabolism is still the most probable explanation for the observed low levels.

Adult↗
PubMed1994

Ulcerative colitis and Crohn's disease: factor XIII, inflammation and haemostasis.

An important role has been ascribed to plasma factor XIII (FXIII) in inflammation and wound healing. FXIII is necessary for fibrin stabilization and interacts with connective tissue and adhesive proteins and cells. In a prospective study, FXIII activity and parameters of coagulation, fibrinolysis and inflammation, were determined in patients with ulcerative colitis (UC; 13 active, 22 moderate) and Crohn's disease (CD; 36 active, 45 moderate). FXIII levels were lower in active than in moderate UC and CD, and were < 70% of normal values in 7/13 patients with active UC, and in 7/36 patients with active CD, although the median values did not fall below the normal range. FXIII was somewhat higher in active UC patients responding to therapy. The FXIII levels were widely scattered, and low values appear to be due to greatly enhanced turnover. A correlation between FXIII and the systemic levels of markers of activation of haemostasis and inflammation was lacking, but there was a correlation with the extent of bowel involvement. FXIII levels were lower in the patients with involvement beyond the sigmoid colon in CU (p = 0.0045), and both small and large bowel segments in CD (p = 0.0223) patients. This points to local consumption and/or loss of FXIII within the inflamed tissue, and provides an argument for FXIII substitution in the treatment of acute episodes of inflammatory bowel diseases.

Adolescent↗
PubMed1993

Activators of coagulation in cultured human lung-tumor cells.

Tumor matrix generation and tumor cell growth are supported by coagulation processes within the tumor tissue. Activators of coagulation were searched for in suspensions of 9 permanent human squamous-cell lung-cancer (EPLC 32MI, U1752), large-cell lung-cancer (LCLC 97TMI, LCLC 103H, U1810), and small-cell lung-cancer (N-592, H-526, DMS79, 86MI) cell lines. Incubation with these cells shortened the recalcification time in normal plasma (also in the presence of antibodies against tissue factor) or coagulation-factor-VII-, VIII-, IX- or X-deficient plasmas. The activators of coagulation in the 2 most active cell lines (U1752 and LCLC 103H) were further characterized in purified systems: the cleavage of chromogenic substrates, and the generation of markers of pro-thrombin activation were assessed. Three activators of coagulation were found in intact or sonicated cell suspensions and culture supernatants: (i) a tissue factor (TF)-like activity; (ii) an activity activating factor X, which in contrast to "cancer pro-coagulant" was not inhibited by iodoacetamide; and (iii) an activity-activating pro-thrombin, which was inhibited by the serine protease inhibitor PMSF and appeared to require plasmatic co-factor(s). The heterogeneous expression of coagulation activators by lung-tumor cell lines might be of significance for tumor biology and response to therapy.

Blood Coagulation↗
PubMed1993

Activation of coagulation and fibrinolysis in patients with lung cancer: relation to tumour stage and prognosis.

Activation of coagulation and fibrinolysis within tumour tissues is thought to be associated with tumour growth, angiogenesis, and metastasis. The plasma levels of markers of thrombin and plasmin generation are sensitive tools for monitoring activation of coagulation and fibrinolysis. We studied 47 patients with histologically confirmed lung cancer, 15 with small cell (SCLC) and 32 with non-small cell lung cancer (NSCLC). The plasma levels of the following markers were assessed:thrombin-antithrombin III complex (TAT), prothrombin activation fragment F1 + 2, plasmin-alpha 2-antiplasmin complex (PAP) and the split product from cross-linked fibrin, D-dimer. The first sample was obtained before receiving any specific antineoplastic treatment. The patients were followed thereafter until treatment was terminated. There was no difference in activation markers between patients with SCLC and NSCLC. Comparing patients with limited disease to those with extensive disease, there were significant differences in TAT (median 3.0 (1.9-9.8) vs 5.3 (1.8-35.6) micrograms/l,P = 0.021) and D-dimer (569 (135-1948) vs 1288 (120-2221) micrograms/l, P = 0.014). According to the response to subsequent treatment, those who achieved complete or partial tumour remission had significantly lower baseline levels samples than non-responders (TAT 2.9 (1.9-4.0) vs 4.7 (1.8-35.6) micrograms/l,P = 0.0047;D-dimer 527 (135-1149) vs 1242 (120-2221) micrograms/l, P = 0.0013). Thus, the increase of TAT and D-dimer appears to be related to tumour spread. The results suggest that high levels of these markers might be a sign of unfavourable prognosis in patients with lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1993

Protein S degradation in vitro by neutrophil elastase.

Human protein S is degraded by neutrophil elastase. The characteristics of cleavage are compared in a purified protein S preparation, a concentrate of vitamin K-dependent proteins (PPSB) and in normal plasma as well as in alpha-proteinase inhibitor (alpha PI)- deficient plasma. Elastase incubation of purified human protein S (molar enzyme-to-substrate-ratio 1:5500-1:55) reduces the molar mass of the native protein S (81-83 kDa) to about 79 kDa by cleavage of a small peptide. Incubation with very high elastase concentrations (molar enzyme-to-substrate-ratio 1:5.5) completely degrades protein S into small fragments. The elastase incubated protein S has a higher isoelectric point than the native form (Ip 5.9 vs. 5.3). Protein S in a PPSB coagulation factor concentrate is degraded in the same way as isolated protein S. By immunoblotting also smaller split products of molar masses between 34 and 70 kDa are demonstrated. In normal plasma protein S is not degraded by elastase concentrations up to 14 mumol l-1. In plasma of a patient with alpha 1-proteinase inhibitor deficiency protein S can be degraded by elastase. The native 82 kDa protein is degraded to a 72 kDa protein. PEG precipitation of the protein S- C4b- binding protein-complex shows that elastase predominantly splits the free protein S.

Blood Coagulation Factors↗
PubMed1991

Specification and selection of regions of interest (ROIs) in a computerized brain atlas.

The computerized individually adjustable brain atlas (CBA) has been further developed. The atlas was primarily designed for anatomical localization and quantitative evaluation of data in positron emission tomography (PET), but may also be employed for other neuroimaging modalities, such as transmission computed tomography (CT) and magnetic resonance imaging (MRI). The atlas is based on anatomical information obtained from digitized cryosectioned brains. Using spatially standardized and then averaged MRI images, we demonstrate the high localization accuracy and precision of the brain atlas. This is a prerequisite for obtaining accuracy when using the atlas in the localization and the quantitative evaluation of PET data. The specification and the selection of region of interests (ROIs) by the CBA are presented and discussed.

Brain↗
PubMed1991

Hemodialysis and blood coagulation: the effect of hemodialysis on coagulation factor XIII and thrombin-antithrombin III complex.

Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure.

Acute Kidney Injury↗
PubMed1991

Protein C degradation in vitro by neutrophil elastase.

Purified protein C is completely degraded into small peptides by in vitro incubation with purified elastase. Protein C is a rather sensitive substrate as degradation is already accomplished by low elastase concentrations (molar enzyme-to-substrate ratio 1:510) and short incubation periods (5 min-60 min). Protein C in a PPSB coagulation factor concentrate is equally degraded and similar split products are detected by blotting techniques. The protein C activity (measured by a chromogenic substrate) is faster reduced by elastase than the protein C concentration (measured by an ELISA). Incubation of normal plasma with high elastase concentrations (5.7 nmol/ml plasma) results in reduction of the protein C band while no split products are detectable. The pathophysiologic significance of the effects of elastase on protein C remains to be elucidated.

Blood Coagulation Factors↗
PubMed1991

[Disorders of blood coagulation in the intensive care unit: what is important for diagnosis and therapy?].

In the haemostatic system there is normally a stable balance between its components (vessel wall, platelets, coagulation, fibrinolysis), which are in continuously close interaction. Disturbances of this balance may lead to bleeding, thrombosis, or thrombohaemorrhagic consumptive disorders. The task of haemostaseologic diagnostics is to discover eventual preexisting but as yet undiagnosed disturbances in any patient entering an intensive care unit and, in cases of acute bleeding, to provide useful information that facilitates therapeutic decisions. Furthermore, the recognition of disseminated intravascular coagulation (DIC) in an early, tractable phase may be a matter of life and death. Promising attempts to overcome DIC via substitution of antithrombin III and fresh frozen plasma are discussed. Optimal management of complications and monitoring of therapy requires the close teamwork of attending surgeons or physicians and haemostaseologists. The purpose of any therapy is to preserve or regain the balance of haemostasis.

Blood Coagulation Disorders↗
PubMed1990

Cytochemical determination of intracellular polymorphonuclear leukocyte elastase content in patients with severe bacterial infection and septicaemia correlated with coagulation parameters.

Haemorrhagic disorders are known to occur during septicaemia. We studied the role of elastase-like protease (ELP) of human granulocytes in the activation and consumption of clotting factors and their specific inhibitors. Patients with septicaemia and severe bacterial infection were examined for ELP content in polymorphonuclear leukocytes (PNL), as well as plasma levels of ELP complexed to alpha-1 protease inhibitor, total alpha-1 protease inhibitor (alpha-1 PI), clotting factor VII and partial thromboplastin time (PTT). In all patients, a decrease in ELP content of PNL was accompanied by an increase in plasma ELP complexes. The degree to which ELP content of PNL was lowered was related both to the clinical diagnosis and the course of illness. The ELP content of PNL showed a significant positive correlation with plasma factor VII and significant negative correlations with PTT and alpha-1 PI. These data suggest that ELP release is accompanied by stimulation of the production of alpha-1 PI, and may contribute in vivo to the consumption of coagulation factors. The correlation with PTT might point to an activation of Hageman factor, which may activate both intrinsic coagulation and ELP release. The estimation of ELP content in PNL in patients with septicaemia is likely to represent intravascular ELP release during the inflammatory process. It appears to be useful in combination with the assay of ELP complex in plasma the level of which is influenced by the capacity of the reticuloendothelial system for clearance.

Adult↗
PubMed1990

Improved prognosis of fulminant hepatic failure (FHF) after plasma derivative replacement therapy. Enhanced proteolysis of hemostatic proteins confirmed by proteinase-inhibitor complexes determination.

In fulminant hepatic failure disturbances of blood coagulation are caused by both delayed synthesis and increased consumption of hemostatic proteins. The enhanced turnover of clotting factors and inhibitors may be induced by thrombin and plasmin after activation of the coagulation system by thromboplastic material and activators of plasminogen released from necrotic liver cells. Additionally, proteases such as elastase released from granulocytes, may be involved when infectious complications occur. The immunologic determination of the specific proteinase-inhibitor complexes thrombin-antithrombin III, plasmin-alpha 2 antiplasmin, and elastase-alpha 1 antitrypsin is of great diagnostic value to verify and differentiate the proteolysis of hemostatic proteins. Five patients with FHF were treated with plasma derivatives (FFP and AT III concentrates) until the liver had recovered and resumed synthesis of clotting factors and their inhibitors. The coagulation parameters normalized, bleeding complications and microcirculatory failure could be prevented. The data suggest that a comprehensive substitution of plasma components improves considerably the prognosis of acute liver failure.

Adult↗
PubMed1989

A unique case of intravenous injection of fungal "pancreatic" enzymes causing shock and proteolysis of haemostatic proteins.

A 20-year-old man on oral substitution of pancreatic enzymes after hemipancreatectomy injected an enzyme preparation of fungal origin intravenously after dissolving it in water. Within a few hours chills, headache, nausea and vomiting, fever of 40.8 degrees C, and shock occurred. The acute illness might have been caused by bacteremia, an anaphylactic reaction, or by direct activation of humoral or cellular mediators by the fungal enzymes. A haemostatic disturbance, particularly a drop in plasminogen, was observed. In vitro, the fungal enzyme preparation stimulated elastase release from isolated neutrophils and eliminated plasmatic inhibitors and plasminogen in normal plasma and whole blood. Human neutrophil elastase complexed to alpha 1-antitrypsin was increased in the patient's plasma, while the levels of the complexes thrombin-antithrombinIII and plasmin-alpha 2-antiplasmin, indicating recent coagulation or fibrinolysis, respectively, were not elevated. Thus, an activation of the neutrophils with release of elastase might have contributed to the observed coagulation disturbances.

Adult↗
PubMed1989

Synthesis of [11C]sodium thiocyanate for in vivo studies of anion kinetics using positron emission tomography (PET).

Sodium thiocyanate (NaSCN) was labelled with carbon-11 for in vivo studies of anion kinetics using positron emission tomography (PET). The synthesis was complete in 35 min from end of bombardment using [11C]ammonium cyanide as the labelled precursor. [11C]NaSCN was produced by the reaction of [11C]sodium cyanide with elemental sulfur and subsequently separated by semi-preparative high performance liquid chromatography (HPLC). Radiochemical yields (isolated) were of the order of 25%. The specific activity was 18 GBq/mmol and the radiochemical purity better than 99%. A PET study performed in a healthy volunteer showed distribution of [11C]SCN- to areas corresponding to cortical fluid spaces known to be accessible to inorganic ions such as Cl-. An accumulation of the tracer was observed during the 70 min investigation, indicating at least three compartments of distribution.

Anions↗