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Biomedical subjects

S Schmitz

Publications and source records attributed to S Schmitz.

At least 73 records · Page 4Linked to original sources

Genetic and environmental influences on early childhood behavior.

The Child Behavior Checklist for Ages 2-3 (Adelbach et al., J. Abnorm. Child Psychol. 15;629-650; 1987) was completed by mothers of 229 pairs of twins (mean age = 33 months). Using the two broad-band groupings of Internalizing and Externalizing described by Achenbach et al. (1987), various models to estimate genetic and environmental parameters were fitted using LISREL 7. Model-fitting results showed that the genetic components to the observed phenotypical variation were small and not necessary in the model. Influences from the shared environment, however, could not be dropped from the model without a deterioration in fit. Parameter estimates were not significantly different in boys and girls.

Child Behavior↗

[Long-wave ultraviolet radiation (UVA) and skin cancer].

Ultraviolet light is frequently used for cosmetic tanning of the skin. UV light is known to be carcinogenic, but this is attributed predominantly to short-wavelength UV radiation (UVB). However, new data indicate a carcinogenic role for long wavelength ultraviolet light (UVA) also. In vitro studies have demonstrated DNA-damaging effects of UVA. In animals squamous cell carcinomas and melanomas were induced by UVA alone or in combination with UVB. Reference to a possible carcinogenicity of UVA may also be derived from the therapeutic application of UVA together with psoralens (PUVA). In addition, recent epidemiological studies have associated the use of sunbeds with the development of malignant melanoma. In conclusion, the carcinogenicity of UVA in humans cannot be ruled out, but requires further validation. Long and repeated UVA exposure should be discouraged, because of the far-reaching risks involved.

Animals↗

Transcriptional and translational analysis of ferredoxin and flavodoxin under iron and nitrogen stress in Anabaena sp. strain PCC 7120.

In Anabaena sp. strain PCC 7120, vegetative cell ferredoxin synthesis under iron starvation was repressed 25-fold, whereas heterocyst ferredoxin synthesis decreased only 2.8-fold. Induction of flavodoxin under iron depletion was independent of the availability of combined nitrogen. Under iron stress but in the presence of combined nitrogen, fdxH and nifH genes were transcriptionally active; although excision of the 11-kb element seemed to be completed, nitrogenase activity and the fdxH gene product were not detectable.

Adaptation, Biological↗

Evidence from directed mutagenesis that positively charged amino acids are necessary for interaction of nitrogenase with the [2Fe-2S] heterocyst ferredoxin (FdxH) from the cyanobacterium Anabaena sp., PCC7120.

Sequence comparison of the heterocyst-type ferredoxin (FdxH) from Anabaena 7120 and type-1 ferredoxins (PetF) from the same organism and other cyanobacteria revealed a group of positively charged residues characteristic for FdxH. Molecular modeling showed that these basic amino acids are clustered on the surface of FdxH. The corresponding domain of PetF contained acidic or nonpolar residues instead. To identify amino acids that are important for interaction with nitrogenase, we generated site-directed mutations in the fdxH gene and assayed the in vitro activity of the resulting recombinant proteins isolated from Escherichia coli. In addition to the point mutants, two chimeric proteins, FdxH:PetF and PetF:FdxH, were constructed containing the 58 N-terminal amino acids of one ferredoxin fused to the 40 C-terminal amino acids of the other. Exchange of lysines 10 and 11 of FdxH for the corresponding residues of PetF (glutamate 10 and alanine 11) resulted in a ferredoxin with greatly decreased affinity to nitrogenase. This indicates an important function of these basic amino acids in interaction with dinitrogenase reductase (NifH) from Anabaena. In addition we checked the reactivity of the recombinant ferredoxins with ferredoxin-NADP+ oxidoreductase (FNR) and photosystem I. The experiments with both the chimeric and point mutated ferredoxins showed that the C-terminal part of this protein determines its activity in NADP+ photoreduction.

Amino Acid Sequence↗

Heavy metals as selective inhibitors of mould growth.

Ten heavy metals were tested in malt extract agar for their selective activity on nine food relevant fungi. The variations observed as growth inhibitory for heavy metals investigated indicated good possibility for designing selective media.

Culture Media↗

Quantification of the cell kinetic effects of G-CSF using a model of human granulopoiesis.

Using a mathematical model of normal human granulopoiesis, the most important influences of granulocyte colony-stimulating factor (G-CSF) on the regulation of white cell production can be quantified. G-CSF increases the blood neutrophils via three effects: reduction of the transit time of the postmitotic granulopoietic bone marrow cells; additional mitoses of the early granulopoietic bone marrow cells; and possibly demargination. The application of G-CSF in vivo results in a summation of the single effects. For a G-CSF application of 5 days at a daily dose of 10 micrograms/kg, the reduction of postmitotic bone marrow transit time from 6 days to 1.5 days together with demargination with a rate of 10% per hour explains the initial increase of the blood neutrophils until day 1. Both effects fail to explain the sustained increase thereafter. Enhanced amplification of the early granulopoietic bone marrow cells is also necessary to reproduce the sustained increase. Depending on the individual clinical data, approximately 5 additional mitoses occur, evenly distributed to the myeloblasts, promyelocytes and myelocytes. If the above three effects of G-CSF are assumed, the model predicts bone marrow data in accordance with clinical observations.

Bone Marrow Cells↗

[The incidence of postoperative pain on general surgical wards. Results of different evaluation procedures].

Knowledge of the incidence and significance of postoperative pain is essential for the establishment of effective pain treatment programmes. Detailed investigations on the incidence, severity and quality of postoperative pain from the surgeon's perspective are scarce in German hospitals. It was the aim of our study to investigate postoperative pain in general surgery under routine conditions. PATIENTS AND METHODS. A total of 168 patients scheduled for abdominal, vascular and orthopaedic surgery were investigated in a prospective trial. Pain was assessed by means of a 100-point visual analogue scale (VAS), a 5-point verbal rating scale (VRS), the original version of the McGill Pain Questionnaire (MPQ) and the short form of the McGill Pain Questionnaire (SFMPQ). These were applied preoperatively and daily thereafter up to the 7th postoperative day. Patients were randomly assigned into two groups with different sequences of application of the instruments. The pain treatment programme included intravenous analgesia with tramadol/metamizol (max. tramadol 400 mg+metamizol 5 g in any 24 h) after major surgery and additional administration of piritramide as needed (max. 60 mg/24 h.i.v.). After minor surgery ibuprofen was routinely given for analgesia (3 x 500 mg). RESULTS. All patients had pain on the days 1 and 2 postoperatively. The mean intensity of pain was 44 VAS points on day 1 and 6.8 points on day 7. The mean intensity of pain measured by the VRS on the 1st postoperative day was between "mild" and "moderate". The quality of pain showed a constant pattern concerning the mean scale values of descriptors of each subgroup (sensory, evaluative, affective, mixed) for both the original and the short form of the McGill Pain Questionnaire up to the 7th postoperative day. Sensory descriptors were reported more frequently than affective descriptors. Typical pain patterns were identified for different operations. After subtotal thyroidectomy, for example, patients perceived a high intensity of pain of short duration. In contrast, patients still have a high intensity of pain up to 7 days after abdominal and rectal operations. CONCLUSIONS. We conclude from our results that patients perceive significant postoperative pain under current standardized pain treatment in our department. Effective programmes for pain relief should take account of the different patterns of pain after different operations, as identified in this study.

Adolescent↗

Polyethylene-glycol-mediated delivery of liposome-entrapped pigments into fibroblasts: experimental pigment cells as models for mutator phenotypes.

The role of epidermal melanin pigments in the development of skin cancer remains unclear. A new technique for the specific introduction of compartmentalized melanin into nonpigmented human fibroblasts through the use of liposomes and polyethylene glycol (PEG) is presented. The delivery of liposome-encapsulated material to cells was characterized by: (a) high efficiency of delivery through PEG-mediated endocytosis at 37 degrees C; (b) intracellular acidification of liposome entrapped pH-sensitive 8-hydroxypyrene-3,6,8-trisulfonic acid after delivery; (c) similar incorporation and acidification of apolipoprotein E-associated liposomes into fibroblasts via the low-density lipoprotein-receptor pathway; and (d) discharge into the extracellular space after incorporation. Similar experiments were carried out with melanin-containing liposomes that were used to introduce compartmentalized melanin into fibroblasts, through PEG-mediated delivery. These "artificial" melanocytes had functional analogies to genuine melanocytes in that (a) in both cell types melanin compartmentalization was at a lower pH; and (b) liposome contents were later expelled in analogy to the putative biological process of melanin expulsion from the melanocyte. The modified fibroblasts provided potential "mutator" phenotypes with specific melanin pigmentation, and established a new basis for studying the role of melanin pigmentation in cancer development.

Cell Compartmentation↗

Hematotoxic effects of benzene analyzed by mathematical modeling.

The hematopoietic cell response to benzene intoxication in mice (during and after long-term inhalation) was analyzed by a mathematical model of murine hematopoiesis. Two complementary methods, Time-Curve and Steady-State Analysis, were developed to identify target cells for benzene toxicity and to quantify the extent of damage in different stages of development of these target cells. We found that (i) erythropoietic cells were the most sensitive; (ii) granulopoietic cells were about half as sensitive as erythropoietic and (iii) hematopoietic stem cells exhibited a sensitivity that ranged between that of erythropoietic and granulopoietic cells. A dose-response relationship between benzene levels and damage in target cells (valid from 1 to more than 900 ppm) was derived that was linear for doses up to 300 ppm and plateaued thereafter. This relationship indicated that benzene-induced hematotoxicity is subject to a saturable process. Recovery of hematopoiesis following chronic benzene intoxication was simulated for different doses and preceding exposure periods. The impaired recovery following exposure periods greater than 8 weeks could be explained by a severe reduction in the maximum self-maintenance of stem cells. This study indicates that the present mathematical model represents a useful approach to investigate alternate hypotheses for the action of hematotoxic agents.

Animals↗

A new approach for displaying identities and differences among aligned amino acid sequences.

An algorithm is presented for computing degrees of sequence conservation found among aligned amino acid sequences. Sequence identities are calculated for each position of an alignment and average identity values of neighboring positions are figured. The average identity value of the whole alignment is chosen as a limit to discriminate between well and less conserved sequence sections. A second algorithm is given to calculate the degree of divergence of individual sequences compared to the other sequences of the alignment. The approach is easy to use on microcomputers and gives an exact picture of sequence identities and differences in order to determine, first, protein regions of high functional or structural importance among homologous proteins, and, second, significant differences of single sequences that may contribute to individual properties of the analysed protein. The method is illustrated by an example analysing a sequence alignment of higher plant nitrate reductases.

Algorithms↗

Analysis of carbamazepine and its 10,11-epoxide in serum by direct sample injection using surfactant containing eluents and column switching.

Column switching is used in conjunction with surfactant containing mobile phases and traditional reverse phase LC columns to provide a highly reproducible and accurate analytical procedure for carbamazepine and its 10,11-epoxide in serum. This approach eliminates the tedious sample preparation steps commonly used in the analysis of drugs by HPLC, while providing a high degree of protein removal prior to the final analysis. Various pre-columns were investigated and a pellicular reverse phase column was found suitable for optimum concentration of drugs and removal of serum proteins. A variety of standard reverse phase columns could be used for the analytical separation. The separation of the drugs could be accomplished with a high degree of reproducibility. Tandem pre-column operation was demonstrated to give a sample throughput of 10 h-1.

Carbamazepine↗

Analysis of carbamazepine in serum by liquid chromatography with direct sample injection and surfactant-containing eluents.

Surfactant-containing eluents are evaluated for the analysis of carbamazepine in serum with conventional reversed-phase columns. Bovine serum was quantitatively eluted at the column void volume using surfactant concentrations in conventional reversed-phase eluents. The effect of pH, guard columns and column switching was evaluated with respect to separating and detecting clinical levels of the drug and its primary metabolite. Column lifetime was also investigated.

Animals↗

[The value of arthroscopic labrum stapling in anterior shoulder dislocation].

Shoulder luxations are common injuries in relation to sports. Isokinetic strength was evaluated in 24 patients on the average 1 year after performing arthroscopic stabilisation of an anterior shoulder luxation. Using the Merac (Universal Gym Equip., Cedar Rapids, Iowa, USA), test data were gathered on both shoulders in flexion-extension, abduction-adduction and in the supine 90 degrees abducted test position in external-internal rotation. Tests were performed at 60, 180 and 500 deg/sec. Means and standard deviations for peak torque, total work, peak torque to body weight ratios and agonist/antagonist ratios are presented. Our one year follow-up showed, that 82% of all patients were free from complaints and had almost the same data as on the non-operated shoulders. Arthroscopic stabilisation of anterior shoulder luxations in combination with intensive physiotherapy gave excellent results in most cases.

Adult↗

Synchrony of bone marrow proliferation and maturation as the origin of cyclic haemopoiesis.

Cyclic haemopoiesis in Grey Collie dogs is characterized by stable oscillations in all haemopoietic lineages. It is proposed that in these animals, in contrast to normal animals, the maturation process of haemopoietic (in particular granuloid) cells from the primitive progenitors to the functional cells is characterized by an abnormally strong synchrony. It is conjectured that the marrow maturation time has a very small variance compared with non-cyclic normal dogs. With a mathematical model of haemopoiesis it is shown that small fluctuations are amplified via regular feedback processes such that stable granuloid oscillations are established. Erythroid oscillations are induced indirectly by granuloid feedback to the stem cell pool. The model calculations further show that the synchrony hypothesis of bone marrow maturation can quantitatively explain the following experimental results: (1) the maintenance of stable cycles of granuloid and erythroid bone marrow and blood cells with a period of approximately 14 d; (2) the disappearance of granuloid and erythroid cycles during the administration of the colony stimulating factor rhG-CSF; (3) the reappearance of oscillations when the administration of CSF is discontinued; (4) the cessation of cycles during endotoxin application; and (5) the persistence of cycles during erythroid manipulations (bleeding anaemia, hypoxia, hypertransfusion). We therefore conclude that cyclic haemopoiesis is not caused by a defect in the regulatory control system but by an unusual maturation process.

Animals↗