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Biomedical subjects

R Seitz

Publications and source records attributed to R Seitz.

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

Mechanisms of shockwave action in the human kidney.

The effects on the human kidney parenchyma of high-energy shockwaves (HESW) with different energy densities were examined. Kidneys of patients treated by radical nephrectomy for renal cell carcinoma were perfused with cold HTK solution immediately after nephrectomy and kept in hypothermia (8 degrees C) for a maximum of 4 hours. The tumor-free parenchyma was treated with 2000 shocks at energy outputs of 15 kV (16 MPa, 0.15 mJ/mm2), 17 kV (32 MPa, 0.25 mJ/mm2), 19 kV (50 MPa, 0.4 mJ/mm2), and 21 kV (65 MPa, 0.6 mJ/mm2) in an experimental electromagnetic shockwave system (Siemens Co., Erlanger, Germany). Resulting tissue effects were analyzed by histologic and immunohistochemical examinations and confocal laser scanning microscopy. Different sensitivities of cell components, blood vessels, and tubules were found. Laser scanning microscopy revealed nuclear alterations in the vicinity of the focus up to a distance of approximately 10 mm. Severe histologic changes were found in a smaller zone, while immunohistochemistry studies revealed negative collagen IV staining in an area of approximately 4 x 4 mm (all distances measured within the plane perpendicular to the acoustic axis). From these results, it can be concluded that HESW directly damage the tubules and the vascular system, which might explain the clinical changes after extracorporeal shockwave lithotripsy in human patients. The extent of these effects seems to be dependent on the applied energy.

Carcinoma, Renal Cell↗
PubMed1995

Clinical and biochemical analysis in infection-associated stroke.

BACKGROUND AND PURPOSE: Currently, recent infection (primarily bacterial infection) is discussed as a risk factor for cerebrovascular ischemia. The aim of this study was to investigate whether the association of ischemic stroke with recent infection is restricted to stroke subtypes and whether recent infection influences the severity of the postischemic deficit; we also aimed to define biochemical pathways linking infection and ischemic stroke. METHODS: Analyzing the data of a prospective case-control study, we classified the etiology of cerebrovascular ischemia on the basis of clinical, neuroradiological, sonographical, cardiological, and biochemical data in 159 patients without and in 38 patients with infection within 1 week before ischemia. We assessed the severity of neurological deficits using the Scandinavian Stroke Scale. RESULTS: In patients with recent infection compared with patients without infection, the neurological deficit on admission was more severe (median of scores, 41 versus 30.5; P < .005), cortical infarcts in the middle cerebral artery territory were more frequent (60% versus 26%; P < .001), the prevalence of extracranial artery stenoses was lower (9% versus 26%; P < .05), and definite or presumed cardioembolic stroke was more frequent (34% versus 19%; P < .05), as was stroke from cervical artery dissection (8% versus 1.3%; P = .05). Serum levels of C-reactive protein were higher in patients with (20.7 +/- 26.8 mg/L) than in those without infection (9.2 +/- 23.7 mg/L; P < .01). CONCLUSIONS: Recent infection may be associated with a more severe postischemic deficit and with an increased risk of stroke from cardioembolic origin and from cervical arterial dissection.

Adolescent↗
PubMed1995

D-dimer tests detect both plasmin and neutrophil elastase derived split products.

Both plasmin and elastase, a protease released from neutrophil granulocytes, are known to degrade fibrin(ogen). This raises the possibility that elevated plasma levels of split products such as D-dimer may in part result from elastase action. After incubation in vitro of fibrinogen and fibrin clots with elastase, a clearcut increase of D-dimer immunoreactivity was demonstrated by two commercial ELISA kits. In the plasma of 79 patients with inflammatory bowel disease, D-dimer values measured by one of the ELISA kits were correlated significantly not only with markers of thrombin and plasmin activation, but also with elastase-alpha 1-antitrypsin complexes (r = 0.3555; P = 0.014). Thus, the findings of this study suggest that indeed the D-dimer levels in patients with inflammatory disorders are influenced by neutrophil elastase. New tests discriminating effects of activated haemostasis from proteolysis by neutrophil enzymes might be helpful in differential diagnosis and monitoring of therapy.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

Tumor cell-induced platelet aggregation in vitro by human pancreatic cancer cell lines.

BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is considered to be a critical step in hematogenous metastasis. METHODS: TCIPA was studied in vitro in six human pancreatic carcinoma cell lines (PC 3, PC 44, AsPC1, BxPC3, Capan2, Panc1). RESULTS: Whereas all cell lines induced aggregation of washed platelets in the presence of minimal amounts of platelet-poor plasma, five cell lines also induced aggregation of platelets in platelet-rich plasma. The thrombin-antagonist hirudin inhibited TCIPA in all cell lines indicating that TCIPA is thrombin-dependent. Since pretreatment of tumor cells with phospholipase A2 or C inhibited TCIPA, the thrombin-generating activity might be confined to the tumor cell surface. Further support for a prothrombinase activity was provided by the observation that all cell lines were able to induce the aggregation of washed platelets after addition of purified coagulation factors II and V. CONCLUSIONS: Pancreatic carcinoma cells are able to induce platelet aggregation via activation of thrombin. This might support metastasis in pancreatic cancer and possibly explain the incidence of thrombosis in this tumor.

Antithrombins↗
PubMed1995

Mapping of human and macaque sensorimotor areas by integrating architectonic, transmitter receptor, MRI and PET data.

The human and macaque sensorimotor cortex was subdivided into numerous areas by a correlative analysis based on cytoarchitectonics, myeloarchitecture and the distribution of transmitter receptors. Receptor densities and laminar distribution patterns differ not only between motor and somatosensory regions, but also between different areas within these regions of the cortex. Changes in receptor distribution often match architectonically defined borders. Receptor findings provide new criteria for a more detailed mapping in the human brain which cannot be achieved by cytoarchitectonic analysis alone. Morphological data on these areas were integrated with functional data from positron emission tomography (PET) on the basis of a recently developed computerised brain atlas. The central sulcus marks the border between (1) the agranular motor cortex with a generally low density of glutamatergic, muscarinic, GABAergic and serotoninergic receptors, and (2) the granular somatosensory cortex with higher densities of these receptors. Rostral to the primary motor cortex, 2 isocortical areas are found on the mesial cortex which probably represent the functionally defined supplementary motor areas (SMA) SMA-proper (caudally) and pre-SMA (rostrally). Below SMA-proper the areas 24d (macaque) and the caudal cingulate motor area cmc (human) are located in the cingulate sulcus. Both regions correspond to the 'posterior cingulate motor areas' of recent PET studies and to the posterior part of the agranular cingulate cortex of architectonic studies. Below pre-SMA the area 24c (macaque) and the rostral cingulate motor area cmr (human) are located in the cingulate sulcus; they correspond to the 'anterior cingulate motor areas' of recent PET observations and to the anterior part of the agranular cingulate cortex of architectonic studies. Homologous sensorimotor areas can be defined in both species on the basis of common architectonic features.

Animals↗
PubMed1994

Refolding of human class II major histocompatibility complex molecules isolated from Escherichia coli. Assembly of peptide-free heterodimers and increased refolding-yield in the presence of antigenic peptide.

The alpha- and beta-chains of the heterodimeric major histocompatibility complex molecules HLA-DRB5*0101 and DRB1*0101 were expressed separately in Escherichia coli. The cytoplasmic and membrane-spanning domains of both chains were replaced by oligohistidine tags to allow purification by metal chelate chromatography. The recombinant proteins were refolded to peptide-free, water-soluble heterodimers by removal of major amounts of detergents and concomitant reoxidiation of disulfide bonds. Correct conformation was documented by three criteria: (a) affinity binding experiments using the antibody L243, which is known to recognize a conformational epitope formed only by correctly associated heterodimers; (b) specific binding of peptides to the refolded molecules; (c) recognition of peptides bound to refolded HLA-DR molecules by T-cells as reflected by Ca2+ influx into T-cells and production of interferon-gamma. The refolding reaction did not absolutely depend on the presence of peptides. The yield of peptide-free heterodimers was 3.0%. However, the yield of refolded heterodimer was increased to 10% if refolding was performed in the presence of antigenic peptides.

Amino Acid Sequence↗
PubMed1994

Use of a computerized brain atlas in magnetoencephalographic activation studies.

A pilot study was carried out to test the feasibility of an adjustable computerized brain atlas, adapted to the individual anatomy for localizing current dipoles by means of magnetoencephalography (MEG). The atlas can be adapted to individual computed tomography (CT) or magnetic resonance (MR) images. Position information is transferred between these imaging methods and MEG using a stereotactic technique. For this purpose, a special non-magnetic helmet was designed to be used together with the ordinary head fixation system. It seems likely that the proposed combination of the brain atlas with MEG, CT and MRI methods will become a powerful tool in exploring different brain functions.

Anatomy, Artistic↗
PubMed1994

Inter-subject variability of cerebral activations in acquiring a motor skill: a study with positron emission tomography.

Cerebral structures activated during sequential right-hand finger movements were mapped with regional cerebral blood flow (rCBF) measurements by positron emission tomography (PET) in individual subjects. Nine healthy volunteers were examined twice; after initial learning and after practicing the finger movement sequence for more than 1 h. Task-specific activation sites were identified by statistical distributions of maximal activity and region size in rCBF subtraction images. A consistent task-specific activation in all nine subjects was detected in the contralateral sensorimotor cortex at an average movement rate of 3.2 Hz reached after practice. This corresponded to a significant increase of the mean rCBF in the left primary sensorimotor cortex in spatially standardised and averaged PET images. Additional task-specific activation sites detected by individual analysis were found in the lateral and medial premotor, parietal, and cingulate areas, and in subcortical structures including the basal ganglia of both cerebral hemispheres. These activations showed no or little spatial overlap from subject to subject, thus being obscured in the analysis of pooled data. The observed activity patterns were related to movement rate and accuracy in individual subjects. It is suggested that the rCBF changes associated with acquisition of a motor skill in individual humans may correspond to plasticity of sensorimotor representations reported in monkeys.

Adult↗
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↗