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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 505 records · Page 28Linked to original sources
PubMed1989

Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2.

The macrophage-activating properties of murine recombinant granulocyte-macrophage (GM)-CSF were studied in murine peritoneal macrophages with respect to metabolism, endocytosis, PGE2 and TNF-alpha release, and tumor cytotoxicity. GM-CSF was found to be a potent stimulus for RNA and protein synthesis, glucose consumption, pinocytosis, and FcR-independent phagocytosis. Macrophages were activated by GM-CSF to kill TNF-alpha-insensitive Eb lymphoma cells but failed to generate cytotoxicity against TNF-alpha-sensitive L929 cells. Although GM-CSF alone was incapable of stimulating TNF-alpha release, it primed macrophages for elevated TNF-alpha production in response to IFN-gamma plus LPS. The priming effect of GM-CSF disappeared upon longer incubation (greater than 12 h) and was followed by a strongly reduced responsiveness to stimuli that release TNF-alpha. Late-stage suppression could be reverted by treatment with the cyclooxygenase blocker indomethacin, and GM-CSF-induced priming for enhanced TNF-alpha release was entirely restored. The responsible arachidonic acid product mediating suppression was found to be PGE2, because 1) GM-CSF-primed macrophages released enhanced amounts of PGE2 and 2) indomethacin-restored macrophages were again suppressed when exogenous PGE2 was added back in amounts produced by GM-CSF-primed macrophages. Although GM-CSF potently induced TNF-alpha gene transcription by 20 h of treatment, PGE2 interfered with translation into the secreted TNF-alpha protein. These data show that GM-CSF is capable of priming for the enhanced release of two factors, initially for TNF-alpha and subsequently for PGE2. The temporally delayed generation of these two mediators suggests an autoregulatory circuit in which the later produced PGE2 limits GM-CSF-induced macrophage activation.

Animals↗
PubMed1989

[The value of endomyocardial biopsy in verifying the diagnosis of sarcoidosis of the heart].

The evaluation of the results of myocardial biopsy specimens of 24 patients highly suspected of having myocardial sarcoidosis revealed a sarcoid granuloma only in one case. In tapering frequency (60-33%) there has been myocardial scarring, generalized fibrosis, pathological count of mononuclear cells, nuclear hypertrophy, and perivascular fibrosis which all yield unspecific results, but because of lack of another cause are related to sarcoidosis. The specimens of 8 patients have been normal. In contrast to communications in the literature, we cannot recommend endomyocardial biopsy as a routine method to establish heart sarcoidosis, but as a method to exclude other myocardial processes.

Adolescent↗
PubMed1989

[Extracorporeal shockwave lithotripsy. Current status in treatment of kidney calculus disease].

The introduction of extracorporal shock wave lithotripsy has led to a revolution in stone management. After five years of clinical experience with increasing use of second generation lithotripters, the following conclusions can be drawn: There is an increasing tendency to employ ESWL for ureteral calculi, although only 60% of those can be located by ultrasound. In the case of staghorn stones, a differentiated approach is adopted (ESWL-, PCNL-monotherapy or a combination of the two) depending on stone size, localisation, chemical composition, radiodensity, and the state of the collecting system. With almost all second generation lithotripters, ESWL can be performed under i.v.-analgesia. Some machines with a large-aperture shock wave source (i.e. Wolf Piezolith, Edap LT 01, Dornier MPL 9000) even permit painfree treatment without the need for analgesia. However, this is associated with a 30% increase in retreatment rate. Further development of low-cost lithotripters and increasing use of ESWL for biliary stones make it necessary for ever more hospitals to face the question of installing such a machine. In this situation, the choice must be based on the local situation (i.e. number of patients, interdisciplinary use of ESWL).

Humans↗
PubMed1989

Pharmacokinetics and haemostatic status during consecutive infusions of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction.

Pharmacokinetics and systemic effects of recombinant tissue-type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean +/- SD) of 3310 +/- 950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of 2210 +/- 470 ng/ml and 930 +/- 200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380 +/- 74 ml/min, t1/2 alpha was 3.6 +/- 0.9 min and t1/2 beta was 16 +/- 5.4 min. After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, alpha 2-antiplasmin to 25%, alpha 2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 micrograms/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.

Aged↗
PubMed1989

Ribosome binding to inosine-substituted mRNAs in the absence of ATP and mRNA factors.

Incubating ribosomes and eukaryotic initiation factor eIF3 with an inosine-substituted mRNA (where the mRNA secondary structure is strongly reduced) in the absence of ATP and other protein synthesis factors produces a 40 S ribosome.mRNA complex. When Met-tRNAMeti and eIF2 are added, a 60 S ribosome subunit attaches forming an 80 S ribosome.mRNA complex. ATP and the three mRNA factors, eIF4B, cap-site factor, and eIF4A, strongly stimulate the attachment of the 60 S subunit. In the absence of Met-tRNAMeti, the 60-S subunit does not attach, and adding ATP and the mRNA factors inhibits the accumulation of 40 S ribosome.inosine mRNA complexes. These results indicate that a 40 S ribosome, probably in a complex with eIF3, has an intrinsic capacity to attach to mRNA. Further, they suggest that Met-tRNAMeti may interact in a subsequent step to stabilize the 40 S ribosome.mRNA complex and allow the attachment of a 60 S ribosome subunit. Although seen most clearly with the inosine-substituted mRNAs, the 40 S ribosome reaction is also obtained with "guanosine" mRNA. A 40 S ribosome attaches to guanosine mRNA without ATP and mRNA factors when an incubation mixture containing ribosomes, eIF3, and mRNA is fixed with glutaraldehyde. In addition, a 40 S ribosome.guanosine mRNA complex can be obtained without glutaraldehyde in incubations containing ATP and the three mRNA factors in the absence of Met-tRNAMeti. The latter reaction is limited because of the instability of the 40 S ribosome.mRNA complex in the absence of Met-tRNA. Nevertheless, its authenticity is indicated by its full dependence upon ATP and the three mRNA factors. The lack of factor requirement for the formation of 40 S ribosome complexes with inosine-substituted mRNAs indicates that ATP and the three mRNA factors function primarily to unwind the secondary structure of a guanosine mRNA. Data relevant to a role for ATP in facilitating ribosome migration on an mRNA are also discussed.

Adenosine Triphosphate↗
PubMed1989

[Stress testing of long-term type I diabetic patients with radionuclide ventriculography].

Left ventricular function was assessed by means of radionuclide ventriculography in 42 patients with long-standing (13 +/- 5 yrs) insulin-dependent diabetes mellitus and in eleven healthy age matched control subjects. Only diabetics were included in the study without diabetes related cardiac risk factors such as hypertension and CAD in order to evaluate diabetes specific changes of cardiac function. No differences were seen between diabetics and controls concerning heart rate and functional parameters of left ventricle in systole and diastole. The rapid filling period was not prolonged. According to our radionuclide data there is no evidence of diabetes related impairment of ventricular function in young patients with long-standing type-1-diabetes mellitus.

Adult↗
PubMed1989

Further delineation of the Nijmegen breakage syndrome.

We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a "bird-like" face, immunological defects involving both the humoral and cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X-rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia nor telangiectasia, and in contrast to the situation in AT the alpha-fetoprotein level in their serum is normal.

Abnormalities, Multiple↗
PubMed1989

The contraction fraction (CF) in myocardial studies with technetium-99m-isonitrile (MIBI)--correlations with radionuclide ventriculography and infarct size measured by SPECT.

Criteria for the detection of coronary artery disease in nuclear cardiology include visualization of perfusion defects and functional impairment of contraction. The purpose of this study is to combine both methods in one procedure with the new myocardial perfusion tracer, 99mTc-methoxy-isobutyl-isonitril (MIBI), reducing time and radiation burden to the patient. Following an uncomplicated recovery, ten patients with first myocardial infarction participated in this study. Radionuclide ventriculography (RNV) was performed at rest and during exercise. Within 2-3 days, 370 MBq 99mTc-MIBI were injected and SPECT acquisition commenced 1 h later. Data processing included a scar image in polar coordinates. Areas of significantly reduced tracer uptake were expressed as a percentage of the total myocardial area. Directly following SPECT, resting and maximum exercise gated planar LAO images were recorded and the contraction was quantified. The concept of the contraction fraction (CF) rested on the end systolic change in count distribution: their increase in density and their centripetal concentration. For comparison, geometrical inner edge detection techniques were also applied. All algorithms for describing an EF equivalent were verified by computer simulations, showing a perfect correlation over a wide range of preset EFs. When applied to the patient studies only the non geometric methods revealed a good correlation with the ejection fraction (EF) obtained by RNV, and with the infarct size measured by SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1989

Cytochemical changes in a human arterial proteoglycan related to atherosclerosis.

The cuprolinic blue (CB) staining method has been used to visualize and characterize proteoglycans (PG) in the extracellular matrix (ECM) of normal and atherosclerotic human arteries. Arterial tissues of 13 individuals (1-83 years of age) were obtained by autopsy. For electron microscopic visualization of PGs staining with CB was performed in the presence of a critical electrolyte concentration of 0.3 M MgCl2. Under these conditions CB selectively interacts with the polysulfated glycosaminoglycan (GAG) side chains of the molecules. Removal of PG side chains by GAG-degrading enzymes prior to CB staining selectively prevented the formation of chondroitin sulfate (CS)-rich and dermatan sulfate (DS)-rich PG-CB precipitates. The DS-rich type of PG is mainly associated with collagen fibrils, the CS-rich type of PG is preferentially localized in nonfibrous areas of the ECM (soluble matrix). When normal arterial tissues are compared with those affected by atherosclerosis quantitative and qualitative changes of PG-CB precipitates are detected. In fibrous plaques a strong accumulation of a large CS-rich type of precipitate close by smooth muscle cells (SMC) and foam cells is observed. In addition, these precipitates are significantly longer in fibrous plaques than in adjacent normal media (116 nm vs. 100 nm; P less than 0.001). This alteration is independent of the age of the donor. Small DS-rich PG-CB precipitates associated with collagen fibrils show strong variations in their length, but not a significant tendency towards elongated precipitates in atherosclerosis. The present results demonstrate that ultracytochemical and morphometric analysis are useful in providing information on the diverse types, locations, interactions, and possibly of molecular changes of PGs in normal and atherosclerotic human arteries.

Arteries↗
PubMed1989

Discrimination of antibodies against antigens of different MHC loci in human sera by monoclonal antibody-specific immobilization of leukocyte antigens.

To detect human antibodies against antigens of different major histocompatibility complex loci, particularly of class II specificity, a newly developed enzyme immunoassay for platelet antibodies was adapted for the use of lymphocytes as target cells. Peripheral blood lymphocytes, phytohemagglutinin-stimulated T cells, or Epstein-Barr virus-transformed B cells were simultaneously incubated with a monomorphic class- or locus-specific monoclonal antibody and the human antibody to be investigated. After solubilization, cell lysates were transferred to an enzyme-linked immunosorbent assay tray coated with a goat anti-mouse Ig antibody. Following immobilization of the monoclonal antibody/antigen complexes, human major histocompatibility complex antibodies were detected by addition of enzyme-labeled goat anti-human Ig. By means of this technique human antibodies against different major histocompatibility complex molecules present in the same sample could be clearly distinguished. Application of the monoclonal antibody-specific immobilization of lymphocyte antigens assay is presented by several examples. Of these, identification of DP-specific antibodies as well as serological DP typing are of particular interest.

Antibodies, Monoclonal↗
PubMed1989

DNA-content, inflammatory tissue response and tumour size in human lung carcinoma.

Tumour imprints of 75 resection specimens with human lung carcinoma (lobe and lungs) were fixed with alcohol and Feulgen-stained. Resection specimens were cut into serial sections 6 mm thick and tumour mass, tumour involvement into intrapulmonary and extrapulmonary lymph nodes, detailed pTN-stage were determined. DNA-content, DNA-index, percentage of diploid/hyperploid tumour cells, and morphometric nuclear features were measured using an automated image analyzing system (VISIAC). Only 10% of the measured carcinomas were diploid. The DNA-index showed the broadest variance in large cell anaplastic carcinoma (1.2-3.3). Carcinomas growing predominantly within the alveolar space, i.e. without destroying the interstitial tissue showed a lower DNA-content above 3c and above 5c compared to carcinomas destroying the interstitial tissue. Carcinomas with severe stroma reaction were found to have 33%-48% of DNA above the 3c value whereas carcinomas without stromal reaction had a percentage above 3c ranging 46%-64% (confidence limits, p less than 0.05). DNA-index increases with increasing tumour volume and decreases for large tumours (greater than 100 ccm). Hyperploid and polyploid tumours were found more frequently in case of pT2 and pT3-stages compared to pT1-stages. No relation of DNA-content or ploidy was found to lymph node involvement and inflammatory response of host tissue.

Carcinoma, Bronchogenic↗
PubMed1989

[Plastic surgery correction of combination craniofacial malformations. A survey for the obstetrician].

Complex malformations of the skeleton of the cranium and face are mostly first discovered by the obstetrician. Almost all anomalies can be corrected already at infant age by means of update craniofacial surgery, provided they are diagnosed well in time and treatment is initiated directly. Surgery should be performed by a team that is well-versed in craniofacial surgery. A few examples are given to illustrate the most important malformations. Pointers to the best possible time of operation, indication and method are supplied.

Acrocephalosyndactylia↗
PubMed1989

Validation of continuous-wave Doppler measurements of mitral valve gradients during exercise--a simultaneous Doppler-catheter study.

In patients with mitral stenosis, continuous-wave Doppler measurements of the maximal transmitral inflow velocity can be converted into transvalvular pressure gradients using the modified Bernoulli equation. Because of close correlations between Doppler- and catheter-measured gradients this method has become a valuable tool in non-invasive evaluation of mitral stenosis at rest. However, in some patients, exercise studies are necessary to determine the haemodynamic significance of the valve stenosis. The accuracy of continuous-wave Doppler in this setting has not yet been validated. Thus, in 20 selected patients with pure or predominant mitral stenosis, continuous-wave Doppler echocardiography was performed during left- and right-heart catheterization. At rest and during submaximal bicycle exercise, Doppler and pressure measurements were simultaneously performed. The Doppler gradient was calculated according to the modified Bernoulli equation while the mean manometric gradient was determined from the simultaneous pulmonary wedge and left ventricular pressure curves. Exercise caused a significant increase of cardiac output (4.8 +/- 1.3 to 5.7 +/- 1.31 min-1) and heart rate (59.7 +/- 12.0 to 95.3 +/- 14.3 beats min-1). The mean Doppler gradient increased from 6.8 +/- 2.1 to 12.2 +/- 3.2 mmHg. The manometric gradient showed a comparable increase of 9.5 +/- 2.4 to 17.2 +/- 3.7 mmHg, respectively. Correlation between Doppler and manometric data was close (y = 0.79x-0.67,r = 0.90,SEE = 0.97 mmHg) at rest and still good during exercise (y = 0.71x-0.10,r = 0.82,SEE = 1.97 mmHg). Thus, in some patients with borderline resting gradients and valve areas, exercise Doppler might allow further identification of the haemodynamic severity of mitral stenosis.

Adult↗
PubMed1989

Characterization of two soybean repetitive proline-rich proteins and a cognate cDNA from germinated axes.

We have resolved and analyzed two proline-rich proteins isolated from the walls of soybean cells in culture. The proteins are similar in amino acid content, containing 20% proline, 20% hydroxyproline, 20% lysine, 16% valine, 10% tyrosine, and 10% glutamate. The proteins undergo a rearrangement or a limited cleavage in dilute NaOH, but are otherwise remarkably stable to a high concentration of alkali. We have cloned and sequenced a cDNA from soybean axes germinated for 31 hours (1A10-2) coding for a protein that closely corresponds in its amino acid content to that of the proline-rich proteins. The cDNA sequence predicts a decameric repeat of Pro-Pro-Val-Tyr-Lys-Pro-Pro-Val-Glu-Lys. Consequently, this class of proteins is referred to as repetitive proline-rich proteins, i.e., RPRP2 and RPRP3. We have also analyzed RNA gel blots with probes that discriminate between the new cDNA clone and a related cDNA previously reported [SbPRP1; Hong, Nagao, and Key (1987). J. Biol. Chem. 262, 8367-8376]. Messenger RNAs from young seedlings and from soybean suspension cultures correspond primarily to the new RPRP clone (1A10-2), whereas the predominant mRNA accumulating later in the roots corresponds to SbPRP1.

Amino Acid Sequence↗
PubMed1989

Activation of macrophages in an experimental rat model of arthritis induced by Erysipelothrix rhusiopathiae infection.

Infection of Lewis rats with Erysipelothrix rhusiopathiae represents an experimental model system of acute and chronic arthritis. We studied here the acute inflammatory phase with respect to stimulation of macrophages and lymphocytes. Intragluteal injection of viable E. rhusiopathiae (10(2) to 10(4) bacteria) rapidly induced generalized inflammation, loss of body weight, hind leg arthritis, and systemic macrophage activation within 2 to 3 days. The same symptoms could also be evoked by injection of dead E. rhusiopathiae. Ex vivo, peritoneal macrophages released large amounts of tumor necrosis factor alpha on day 2 and interleukin-1 on day 3, whereas production of prostaglandin E2 was delayed to days 5 to 7 and appeared to counteract tumor necrosis factor alpha synthesis. The inflammatory response and development of arthritis were strongly dependent on T lymphocytes, as evidenced by the following findings: (i) lymphocytes released lymphokines that activated macrophages to enhanced mediator release; (ii) treatment of rats with cyclosporin A reduced infection-induced macrophage activation; (iii) mitogen-stimulated thymocyte proliferation was enhanced, indicating an infection-induced maturation-differentiation process in the thymus; and (iv) in T-cell-deficient nude rats, a higher dose of bacteria was required for infection, the inflammatory response was less severe, and only mild, but not chronic, arthritis developed. Thus, an E. rhusiopathiae-induced inflammation in rats provides a useful tool to characterize activated macrophages and T lymphocytes during the development of acute arthritis and its transition into the chronic form.

Animals↗
PubMed1989

[Lipid-lowering and anti-aggregating effect of low-dose therapy with fish oil].

Fifteen healthy volunteers were treated for 30 days with 5 g daily fish oil in capsule form (MaxEPA). After that time, serum triglycerides had decreased by a mean of 26% (p less than 0.05). This relative decrease in triglycerides was the larger the higher were the baseline levels before the start of therapy (p less than 0.01). Total cholesterol remained unchanged with fish oil. HDL-cholesterol showed a small mean increase by 12% (p less than 0.10). The rate of platelet aggregation after induction with collagen 1 microgram/ml was reduced after 30 days of therapy (p less than 0.05), while no effect on platelets was observed with collagen 5 micrograms/ml or ADP (0.5, 1 and 10 mumol/l) as aggregating agents. In vitro thromboxane synthesis after stimulation with collagen (1 microgram/ml) or arachidonic acid (1 mmol/l) was inhibited cumulatively by fish oil and, after 30 days, reached 56% (p less than 0.02) and 44% (p less than 0.05) of the initial values, respectively. Both the basal and prostaglandin E1 stimulated concentrations of c-AMP in platelet rich plasma remained uninfluenced. Thus, the ingestion of a low dose of fish oil by young and healthy subjects led to significant changes in serum triglycerides and platelet function.

Administration, Oral↗