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Biomedical subjects

K Schmidt

Publications and source records attributed to K Schmidt.

At least 109 records · Page 6Linked to original sources
PubMed2000

[Explanation of an unclear neurological syndrome by toxicologic investigation].

HISTORY AND CLINICAL FINDINGS: A 51-year-old man without relevant previous illness developed vomiting and diarrhoea, later also tingling and hypaesthesias in the limbs, as well as optical hallucinations that had occurred after a mid-day meal and drinking red wine. Neurological examination revealed variable pupillary reactions with anisocoria that would change from one side to the other. There was no paresis, muscle reflexes were brisk, more so on the right. Babinski reflex was positive on the right, there was an unsustained clonus of the right foot and the coordination tests were normal. Distal symmetrical hypaesthesias and paraesthesias were present in all limbs. An exogenous psychosis with restlessness and optical hallucinations was observed. INVESTIGATIONS: Routine blood count revealed leukocytosis. Serum concentrations of cGt and GPT were raised. Cerebral computed tomography and cerebrospinal fluid as well as microbiological tests of the mid-day meal were normal. DIAGNOSIS, TREATMENT AND COURSE: As the cause of the symptoms was initially unclear the patient was admitted to hospital and monitored without any specific treatment. Within one night all symptoms had disappeared and he was discharged the next morning without any complaints. Later the red wine which he had drunk was examined toxicologically and found to contain the "designer drug" DOB (2,5-dimethoxy-4-bromamphetamine). CONCLUSION: Accidental poisoning with DOB is probably a rare event which can hardly be included in routine differential diagnosis. If an acute cerebral organic syndrome has been excluded, only toxicological investigation can help in establishing the diagnosis in such cases.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2000

Purification and biochemical characterization of a basic superantigen (SPEX/SMEZ3) from Streptococcus pyogenes.

A potent basic superantigen (designated streptococcal pyrogenic exotoxin X, SPEX/SMEZ3) was purified to homogeneity from culture supernatants of a Streptococcus pyogenes scarlatina strain of type 12 (genotype speA(-), speC(-)) and characterized. Sequence alignments revealed SPEX to be an allele of the streptococcal mitogens type Z (SMEZ). The N-terminal amino acid sequence of SPEX was found with LEVDNNSLLR to be identical to the recently described acidic superantigen SMEZ. Although SPEX/SMEZ genes were present in all of the streptococcal strains tested, a toxin production could only be detected in a small number of strains. The produced toxin concentration in the culture supernatants of positive strains differed between 0 and 20 ng ml(-1). The purified SPEX stimulated human T-lymphocytes with Vbeta8 specificity at extremely low concentrations (lower than 100 pg ml(-1)).

Amino Acid Sequence↗
PubMed2000

Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase and nitric oxide synthase.

Tetrahydrobiopterin [(6R)-5,6,7,8-tetrahydro-L-biopterin, H(4)biopterin] is one of several cofactors of nitric oxide synthases (EC 1.14.13.39). Here we compared the action of N(5)-substituted derivatives on recombinant rat neuronal nitric oxide synthase with their effects on dihydropteridine reductase (EC 1.6.99.7) and phenylalanine hydroxylase (EC 1.14.16.1),the well-studied classical H(4)biopterin-dependent reactions. H(4)biopterin substituted at N(5) with methyl, hydroxymethyl, formyl and acetyl groups were used. Substitution at N(5) occurs at a position critical to the redox cycle of the cofactor in phenylalanine hydroxylase/dihydropteridine reductase. We also included N(2)'-methyl H(4)biopterin, a derivative substituted at a position not directly involved in redox cycling, as a control. As compared with N(5)-methyl H(4)biopterin, N(5)-formyl H(4)biopterin bound with twice the capacity but stimulated nitric oxide synthase to a lesser extent. Depending on the substituent used, N(5)-substituted derivatives were redox-active: N(5)-methyl- and N(5)-hydroxyl methyl H(4)biopterin, but not N(5)-formyl- and N(5)-acetyl H(4)biopterin, reduced 2,6-dichlorophenol indophenol. N(5)-Substituted H(4)biopterin derivatives were not oxidized to products serving as substrates for dihydropteridine reductase and,depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: N(5)-methyl- and N(5)-hydroxymethyl H(4)biopterin inhibited phenylalanine hydroxylase, whereas N(5)-formyl- and N(5)-acetyl H(4)biopterin had no effect. Our data demonstrate differences in the mechanism of stimulation of phenylalanine hydroxylase and nitric oxide synthase by H(4)biopterin. They are compatible with a novel, non-classical, redox-active contribution of H(4)biopterin to the catalysis of the nitric oxide synthase reaction.

Animals↗
PubMed2000

Nitric oxide-induced autoinhibition of neuronal nitric oxide synthase in the presence of the autoxidation-resistant pteridine 5-methyltetrahydrobiopterin.

Nitric oxide synthase (NOS) catalysis results in formation of NO or superoxide (O(2)(-.)) depending on the presence or absence of the cofactor tetrahydrobiopterin (BH4). In the absence of O(2)(-.) scavengers, net NO formation cannot be detected even at saturating BH4 concentrations, which is thought to be due to O(2)(-.) production by BH4 autoxidation. Because the N-5-methylated analogue of BH4 (5-Me-BH4) sustains NOS catalysis and is autoxidation-resistant, net NO formation by the neuronal isoform of NOS (nNOS) can be observed at saturating 5-Me-BH4 concentrations. Here we compare the effects of 5-Me-BH4 on L-citrulline formation, NADPH oxidation, H(2)O(2) production and soluble guanylate cyclase (sGC) stimulation. All activities were stimulated biphasically (EC(50) approx. 0.2 microM and more than 1 mM), with an intermediate inhibitory phase at the same pterin concentration as that required for net NO generation and sGC stimulation (4 microM). Concomitantly with inhibition, the NADP(+)/L-citrulline stoichiometry decreased from 2.0 to 1.6. Inhibition occurred only at high enzyme concentrations (IC(50) approx. 10 nM nNOS) and was antagonized by oxyhaemoglobin and by BH4. We ascribe the first stimulatory phase to high-affinity binding of 5-Me-BH4. The inhibitory phase is due to low-affinity binding, resulting in fully coupled catalysis, complete inhibition of O(2)(-.) production and net NO formation. At high enzyme concentrations and thus high NO levels, this causes autoinhibition. NO scavenging by 5-Me-BH4 at concentrations above 1 mM, resulting in the antagonization of inhibition of NOS, explains the second stimulatory phase. In agreement with these assignments 5-Me-BH4 was found to stimulate formation of a haem-NO complex during NOS catalysis. The observation of inhibition with 5-Me-BH4 but not with BH4 implies that, unless O(2)(-.) scavengers are present, a physiological role for NO-induced autoinhibition is unlikely.

Animals↗
PubMed2000

Dityrosine formation outcompetes tyrosine nitration at low steady-state concentrations of peroxynitrite. Implications for tyrosine modification by nitric oxide/superoxide in vivo.

Formation of peroxynitrite from NO and O-(*2) is considered an important trigger for cellular tyrosine nitration under pathophysiological conditions. However, this view has been questioned by a recent report indicating that NO and O-(*2) generated simultaneously from (Z)-1-(N-[3-aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino) diazen-1-ium-1,2-diolate] (SPER/NO) and hypoxanthine/xanthine oxidase, respectively, exhibit much lower nitrating efficiency than authentic peroxynitrite (Pfeiffer, S. and Mayer, B. (1998) J. Biol. Chem. 273, 27280-27285). The present study extends those earlier findings to several alternative NO/O-(*2)-generating systems and provides evidence that the apparent lack of tyrosine nitration by NO/O-(*2) is due to a pronounced decrease of nitration efficiency at low steady-state concentrations of authentic peroxynitrite. The decrease in the yields of 3-nitrotyrosine was accompanied by an increase in the recovery of dityrosine, showing that dimerization of tyrosine radicals outcompetes the nitration reaction at low peroxynitrite concentrations. The observed inverse dependence on peroxynitrite concentration of dityrosine formation and tyrosine nitration is predicted by a kinetic model assuming that radical formation by peroxynitrous acid homolysis results in the generation of tyrosyl radicals that either dimerize to yield dityrosine or combine with (*)NO(2) radical to form 3-nitrotyrosine. The present results demonstrate that very high fluxes (>2 microM/s) of NO/O-(*2) are required to render peroxynitrite an efficient trigger of tyrosine nitration and that dityrosine is a major product of tyrosine modification caused by low steady-state concentrations of peroxynitrite.

Dimerization↗
PubMed2000

Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation.

Endothelial nitric-oxide synthase (type III) (eNOS) was reported to form an inhibitory complex with the bradykinin receptor B2 (B2R) from which the enzyme is released in an active form upon receptor activation (Ju, H., Venema, V. J., Marrero, M. B., and Venema, R. C. (1998) J. Biol. Chem. 273, 24025-24029). Using a synthetic peptide derived from the known inhibitory sequence of the B2R (residues 310-329) we studied the interaction of the receptor with purified eNOS and neuronal nitric-oxide synthase (type I) (nNOS). The peptide inhibited formation of L-citrulline by eNOS and nNOS with IC(50) values of 10.6 +/- 0.4 microM and 7.1 +/- 0.6 microM, respectively. Inhibition was not due to an interference of the peptide with L-arginine or tetrahydrobiopterin binding. The NADPH oxidase activity of nNOS measured in the absence of L-arginine was inhibited by the peptide with an IC(50) of 3.7 +/- 0.6 microM, but the cytochrome c reductase activity of the enzyme was much less susceptible to inhibition (IC(50) >0.1 mM). Steady-state absorbance spectra of nNOS recorded during uncoupled NADPH oxidation showed that the heme remained oxidized in the presence of the synthetic peptide consisting of amino acids 310-329 of the B2R, whereas the reduced oxyferrous heme complex was accumulated in its absence. These data suggest that binding of the B2R 310-329 peptide blocks flavin to heme electron transfer. Co-immunoprecipitation of B2R and nNOS from human embryonic kidney cells stably transfected with human nNOS suggests that the B2R may functionally interact with nNOS in vivo. This interaction of nNOS with the B2R may recruit the enzyme to allow for the effective coupling of bradykinin signaling to the nitric oxide pathway.

Animals↗
PubMed2000

Citalopram and breast-feeding: serum concentration and side effects in the infant.

BACKGROUND: During treatment of postpartum depression with antidepressant drugs, the mothers often strongly wish to continue breast-feeding although the long-term safety of exposing infants to low doses of antidepressants has not been established. METHODS: Citalopram in breast milk and in the serum of a nursing mother and her infant was determined by high-performance liquid chromatography. RESULTS: During treatment with 40 mg/day of citalopram, the concentration of the drug in milk and serum was 205 ng/mL and 98.9 ng/mL, respectively. Her infant obtained 12.7 ng/mL of citalopram in serum and uneasy sleep was observed. Sleep was normalized when the dose was halved and two breast-feedings were replaced with artificial nutrition. CONCLUSION: The amount of citalopram and other selective serotonin inhibitors (SSRIs) passed to breast milk and delivered to the child correlates to the serum concentration of the mother. The lowest possible effective serum concentration should be used and breast-feeding during the drug absorption phase may be avoided.

Adult↗
PubMed2000

Selection of an adaptive test statistic for use with multiple comparison analyses of neuroimaging data.

Statistical analysis of neuroimages is commonly approached with intergroup comparisons made by repeated application of univariate or multivariate tests performed on the set of the regions of interest sampled in the acquired images. The use of such large numbers of tests requires application of techniques for correction for multiple comparisons. Standard multiple comparison adjustments (such as the Bonferroni) may be overly conservative when data are correlated and/or not normally distributed. Resampling-based step-down procedures that successfully account for unknown correlation structures in the data have recently been introduced. We combined resampling step-down procedures with the Minimum Variance Adaptive method, which allows selection of an optimal test statistic from a predefined class of statistics for the data under analysis. As shown in simulation studies and analysis of autoradiographic data, the combined technique exhibits a significant increase in statistical power, even for small sample sizes (n = 8, 9, 10).

Algorithms↗
PubMed2000

Bacterial population of chronic crural ulcers: is there a difference between the diabetic, the venous, and the arterial ulcer?

BACKGROUND: At the Surgical Department of Surgery of the University Hospital Würzburg microbiological examinations were performed of the ulcer grounds from patients with diabetic-neuropathic, diabetic-ischemic, venous, and arterial leg ulcers. The aim of the examination was to evaluate possible differences in the healing process of these ulcers based on the knowledge of their bacterial populations. PATIENTS AND METHODS: In a period of four months, 63 patients were consecutively examined by taking a bacteriological swab of their ulcer area. The healing process of their wounds was followed and related to the impact of bacterial colonisation and clinical signs of infection. RESULTS: 95% of the venous and arterial leg ulcers had a positive smear, whereas only 70% of diabetic ulcers were positive for bacterial growth. Bacterial population of the three ulcer entities, however did not differ significantly. 100% of the clinically infected venous and arterial ulcers but only 80% of the diabetic wounds revealed a positive smear. On the other hand, only 22% of the venous ulcers with a positive smear developed a clinical infection in contrast to 70% of the arterial and diabetic. Venous ulcers showed only in a few patients prolonged healing, even in cases of marked bacterial contamination. Despite of clinical signs of infection however, diabetic wounds sometimes did not reveal a positive wound smear (20%). All infected venous, but only 20% of the infected ischemic ulcers healed satisfactorily. Arterial wounds with no bacterial growth healed significantly better than contaminated wounds. This difference was not significant in the other entities. Radical removal of the infection by minor amputation increased the healing rate in diabetic ulcers over 80%, whereas ischemic wounds did not profit from this therapy. CONCLUSIONS: A positive bacterial wound smear is not inevitably correlated with a protracted leg ulcer healing. Nevertheless a fulminant infection often developed in diabetic ulcers despite the initial inability to demonstrate bacterial growth. In order to start antibiotic treatment as early as possible, a wound smear should be obtained routinely from patients with diabetic ulcers. In chronic venous ulcers, a routine swab does not appear to be indicated as it bears no clinical consequences. The same applies to patients with surgically fully treated peripheral arterial occlusive disease. As ischemia presents the limiting factor, antibiotic therapy in case of infection will not prevent imminent amputation.

Adult↗
PubMed2000

Vascular tracheobronchial compression syndromes-- experience in surgical treatment and literature review.

Between January 1988 and December 1997 a total of 22 patients (age: 8 days-46 years) were operated for vascular airway compression syndromes with respiratory insufficiency. Vascular anomalies in tracheal compression were double aortic arch in 7 patients, (2 previously operated elsewhere), right aortic arch + left ligamentum arteriosum in 1, and pulmonary artery sling in 3. Three of these patients had secondary long-segment tracheomalacia. Compression of trachea and a main bronchus existed in 2 patients with right aortic arch + left ligamentum. Isolated main bronchus obstruction was present in 9 patients (abnormal insertion of ligamentum arteriosum in 1, status post (s.p.) previous operation for PDA in 4, s. p. surgery for coarctation in 1, right aortic arch + left ligamentum arteriosum in 2, and right lung aplasia + left ligamentum in 1). 3 of these cases had secondary long-segment bronchomalacia. All patients had a complex respiratory anamnesis [long-term intubation in 7, s.p. tracheostomy in 2 (over 3 months - 3 years), and progressive respiratory insufficiency in 13). In tracheal compression, surgical correction included transsection of the underlying ring or sling components (with additional anterior aortic arch translocation in 5 patients resection-reimplantation of left pulmonary artery in 3, segmental tracheal resection in 1, and external tracheal suspension in 2). In the 2 cases with compression of the trachea and a main bronchus, aortic "extension" by a prosthetic tube was necessary. In isolated main bronchus obstruction, surgical decompression basically consisted of transsection of the ligamentum arteriosum or resection of its scarry remnant forming the "corner point" of a compression between aorta and pulmonary artery. In 3 patients with secondary long-segment malacia, additional external bronchus suspension was performed. Effective decompression and re-expansion of the airway segment concerned was achieved, and was demonstrated by intraoperative endoscopy in all patients. There were 3 postoperative deaths (sepsis 2; massive, irreversible edema of the tracheal mucosa 1). Of the 19 surviving patients 16 could be extubated between the 1st and 17th (mean = 7.5) postoperative day. In 1 case the preoperative long-term tracheostomy had to be left in place for inoperable additional laryngeal stricture. 2 patients had to be reoperated (segmental cervical tracheal resection after 5 months for primary long-term intubation-related subglottic stenosis in 1, esophageal decompression for residual dysphagia after 57 months related to a traction phenomenon at the right descending aorta in the other), both with gratifying results. In all other patients clinical, endoscopic, and radiographic examinations (follow-up = 2 months - 6 years) demonstrate good results.

Adolescent↗
PubMed2000

Investigation of nonlinear ECoG changes during spontaneous sleep state changes and cortical arousal in fetal sheep.

We examined the processes of cortical activation and deactivation of the fetal brain during spontaneous sleep state transitions and during central nervous processing of vibroacoustic stimulations (VASs) using nonlinear analysis of the electrocorticogram (ECoG). Tests of nonlinearity and a random shuffling routine revealed deterministic and nonlinear portions in the fetal ECoG. As common nonlinear measures are not applicable to nonstationary time series, we developed an algorithm to estimate the predictability of the ECoG in its time course by means of a point prediction error (PPE). The ECoG was recorded before and during VAS from the maternal abdominal surface in seven chronically instrumented fetal sheep at 0.8 of gestation. The PPE during REM sleep was significantly higher than during NREM sleep. VAS in NREM sleep resulted in an abrupt increase of the PPE not reaching the level of REM sleep. The steep increase of the PPE at onset and its slow decrease after cessation of the stimulus were very similar to the dynamics of spontaneous sleep state transitions, suggesting the involvement of the same cortical activating mechanisms. In conclusion, the stage and the time course of fetal brain activation and deactivation patterns can be clearly shown by PPE techniques. The PPE is a useful complement to spectral analysis. Both techniques describe different properties of the ECoG.

Alpha Rhythm↗
PubMed2000

A submembranous matrix of proteoglycans on zymogen granule membranes is involved in granule formation in rat pancreatic acinar cells.

The secretory lectin ZG16p mediated the binding of aggregated zymogens to the granule membrane in pancreatic acinar cells. Using a recently established in vitro condensation-sorting assay, we now show that pretreatment of zymogen granule membranes (ZGM) with either sodium bicarbonate at pH 10 or with phosphatidyl inositol-specific phospholipase C (PI-PLC) reduced the binding efficiency of zymogens to the same extent, as distinct components were liberated from ZGM. Analysis of the composition of the bicarbonate extract revealed the presence of the secretory lectin ZG16p, the serpin ZG46p and the GPI-linked glycoprotein GP-2, together with several unknown proteins, and small amounts of lipase and carboxylester lipase. The unknown proteins detected in 2-D gels represented a group of acidic and basic protein spots, which were positive in a glycan staining reaction and were soluble in methanol. One protein spot of the acidic group and several of the basic group reacted with a monoclonal antibody directed against chondroitin sulfate, indicating that the proteins represented proteoglycans. A staining pattern similar to the glycan reaction was observed in immunoblots using a polyclonal antibody directed against the whole bicarbonate extract. Immunogold electron microscopy revealed that this antibody reacted with components in the periphery of zymogen granules and strongly stained ZGM in the pellet fraction of a standard in vitro condensation-sorting assay. The amino acid composition of isolated components of both the acidic and basic group showed similarities to aggrecan, a cartilage-specific proteoglycan, and to glycine-rich glycoproteins, respectively. We therefore conclude that a submembranous matrix on the ZGM composed of proteoglycans and glycoproteins is involved in granule formation in pancreatic acinar cells.

Animals↗
PubMed2000

Differentiated therapy with prostaglandin E1 (alprostadil) after orthotopic liver transplantation: the usefulness of procalcitonin (PCT) and hepatic artery resistive index (RI) for the evaluation of early graft function and clinical course.

Increasing demand for donor organs has led to new pharmacological concepts for reducing ischemia-reperfusion injury (I/R) of the graft after liver transplantation to prevent primary non-functioning of the organ. Prostaglandins have proved to be cytoprotective in several experimental models of ischemia and transplantation. The prophylactic administration after orthotopic liver transplantation is still a subject of controversial discussion. The aim of our study was the evaluation of the post-transplant hepatic artery resistive index (RI) measured by color Doppler imaging, in combination with postoperative elevation of transaminases, as parameters indicating the need for a differentiated systemic therapy with prostaglandin E1 (PGE1) (alprostadil). In addition, the value of serum procalcitonin (PCT) as a postoperative parameter for the extent of I/R is investigated. In the case of post-transplant elevated hepatic artery RI (RI > 0.75), the administration of PGE1 led to a significant reduction of transaminases (p < 0.05) and a decline of the RI. In addition, postoperative PCT levels could be reduced significantly by PGE1 application. These results suggest that determination of RI is feasible for indicating a need for therapy with PGE1. Its targeted application reduces hepatocellular damage due to I/R after liver transplantation.

Alprostadil↗