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Biomedical subjects

T Steiner

Publications and source records attributed to T Steiner.

At least 91 records · Page 5Linked to original sources
PubMed1997

Deletion analysis of the fis promoter region in Escherichia coli: antagonistic effects of integration host factor and Fis.

Fis is a small DNA-binding and -bending protein in Escherichia coli that is involved in several different biological processes, including stimulation of specialized DNA recombination events and regulation of gene expression. fis protein and mRNA levels rapidly increase during early logarithmic growth phase in response to a nutritional upshift but become virtually undetectable during late logarithmic and stationary phases. We present evidence that the growth phase-dependent fis expression pattern is not determined by changes in mRNA stability, arguing in favor of regulation at the level of transcription. DNA deletion analysis of the fis promoter (fis P) region indicated that DNA sequences from -166 to -81, -36 to -26, and +107 to +366 relative to the transcription start site are required for maximum expression. A DNA sequence resembling the integration host factor (IHF) binding site centered approximately at -114 showed DNase I cleavage protection by IHF. In ihf cells, maximum cellular levels of fis mRNA were decreased more than 3-fold and transcription from fis P on a plasmid was decreased about 3.8-fold compared to those in cells expressing wild-type IHF. In addition, a mutation in the ihf binding site resulted in a 76 and 61% reduction in transcription from fis P on a plasmid in the presence or absence of Fis, respectively. Insertions of 5 or 10 bp between this ihf site and fis P suggest that IHF functions in a position-dependent manner. We conclude that IHF plays a role in stimulating transcription from fis P by interacting with a site centered approximately at -114 relative to the start of transcription. We also showed that although the fis P region contains six Fis binding sites, Fis site II (centered at -42) played a predominant role in autoregulation, Fis sites I and III (centered at +26 and -83, respectively) seemingly played smaller roles, and no role in negative autoregulation could be attributed to Fis sites IV, V, and VI (located upstream of site III). The fis P region from -36 to +7, which is not directly regulated by either IHF or Fis, retained the characteristic fis regulation pattern in response to a nutritional upshift.

Bacterial Proteins↗
PubMed1997

Prognosis of stroke patients requiring mechanical ventilation in a neurological critical care unit.

BACKGROUND AND PURPOSE: Intubation and mechanical ventilation are sometimes necessary during treatment of acute stroke. Indications include neurological deterioration, pulmonary complications, and elective intubation for procedures and surgery. Prognosis in severe stroke patients requiring mechanical ventilation has often been reported to be poor. This study was performed to prospectively assess the prognosis of stroke patients who require ventilation in a neurological intensive care unit and to determine factors that may influence outcome. METHODS: Analysis was made of 124 consecutive stroke patients who required mechanical ventilation over a 2-year period. We determined the survival rate at 1 year after admission. Initial clinical data, history of previous diseases, and indication for intubation were analyzed for prognostic significance by univariate and multiple logistic regression analysis. RESULTS: The 1-year survival rate was 33.1% (n = 41). Sixty-five patients (52%) died in the neurological intensive care unit. Among 17 variables analyzed, seven were found to significantly influence 2-month fatality in the univariate analysis: age greater than 65 years, atrial fibrillation, bilateral absence of pupillary light reflex, bilateral absence of corneal reflex, bilateral Babinski's sign, infratentorial stroke, and Glasgow Coma Scale (GCS) score less than 10. Independent predictors of death at 2 months were age greater than 65 years (P = .03), GCS score less than 10 (P = .01), and intubation performed because of coma or acute respiratory failure (P = .04). CONCLUSIONS: Overall prognosis of ventilated patients with severe stroke is better than previously reported. Older patients comatose on admission who need to be intubated because of neurological or respiratory deterioration have the poorest prognosis. We conclude that intubation and mechanical ventilation of severe stroke patients should be performed in a timely manner, before irreversible damage occurs.

Activities of Daily Living↗
PubMed1997

Brain temperature monitoring and modulation in patients with severe MCA infarction.

BACKGROUND: Brain temperature has been measured only occasionally in humans. After head trauma, a temperature gradient in brain temperature compared with body temperature of up to 3 degrees C degrees higher in the brain has been reported. Elevated temperature facilitates neuronal injury after ischemia. At present, no information concerning changes in brain temperature after acute stroke is available. METHODS: In 15 patients who had suffered severe ischemic stroke in the MCA territory, intracerebral temperature was recorded with use of two different thermocouples, with intraventricular, epidural, and parenchymatous measurements. Body-core temperature (Foley catheter temperature) and jugular bulb temperature (n = 5) were recorded simultaneously. Measures for reducing brain temperature were compared. RESULTS: In all patients, brain temperature exceeded body-core temperature by at least up to 1 degrees C (range, 1.0 to 2.1 degrees C). Temperature in the ventricles exceeded epidural temperature by up to 2.0 degrees C. Brain temperature modulation was independent of single pharmacologic (paracetamol, metamizol) treatments. Only systemic cooling was effective and sustained hypothermic (33 to 34 degrees C) brain temperatures. CONCLUSION: After MCA stroke, human intracerebral temperature is higher than central body-core temperature. There is also a temperature gradient within the brain, with the ventricles warmer than the surface. Mild hypothermia in the treatment of severe cerebral ischemia with use of cooling blankets is both easy to perform and effective in the therapy of severe hemispheric infarction.

Adult↗
PubMed1997

Serum transforming growth factor-beta1 in patients with renal cell carcinoma.

PURPOSE: A major problem of renal cell carcinoma is the prediction of metastases via tumor prognostic markers. Therefore, much effort has been committed to the development of new prognostic markers. MATERIALS AND METHODS: The level of transforming growth factor-beta1 was measured by enzyme-linked immunosorbent assay in serum samples collected from patients with renal cell carcinoma before radical nephrectomy. RESULTS: In serum samples from 21 patients with renal cell carcinoma and 21 healthy controls mean transforming growth factor-beta1 levels were 177 +/- 54.1 versus 65.6 +/- 15.8 ng./ml., respectively. This difference was statistically significant (Mann-Whitney U test p <0.001). CONCLUSIONS: Increased levels of transforming growth factor-beta1 are common in serum of patients with renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1996

Crystal structure of anhydrous hexakis-(2,3,6-tri-O-methyl)-cyclomaltohexaose (permethyl-alpha-cyclodextrin) grown from hot water and from cold NaCl solutions.

An X-ray diffraction study was carried out on anhydrous permethyl-alpha-cyclodextrin crystallized from aq solution at 40 degrees C, space group P2(1)2(1)2(1) with a = 15.424(9), b = 18.167(7), c = 23.128(8) A, vol = 6481(5) A3. The molecule is boat-shaped with the narrow end of the cyclodextrin cavity closed by two diametrically opposing glucose residues. These are strongly tilted towards the molecular axis, so that their primary methoxy groups form van der Waals contacts across the molecular opening. The remaining cavity volume is occupied by the methoxy group of a neighboring molecule (self-inclusion). From solutions containing 1 M NaCl, anhydrous permethyl-alpha-cyclodextrin crystallizes isomorphously at room temperature.

Carbohydrate Conformation↗
PubMed1996

Excess glutamate levels in the cerebrospinal fluid predict clinical outcome of bacterial meningitis.

BACKGROUND: The clinical course of bacterial meningitis still is characterized by a high mortality and frequent neurological deficits in survivors. In addition to other potentially neurotoxic mediators of inflammation, the excitatory amino acid glutamate, which has been implicated in neuronal death in a variety of other neurological diseases, may also be involved in the pathological process of bacterial meningitis. OBJECTIVES: To investigate the prognostic value of the glutamate concentration in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. PATIENTS AND METHODS: Thirty consecutive patients with bacterial meningitis were included in a prospective study. The clinical severity of the disease was assessed on admission and 14 days after the beginning of antibiotic treatment by means of the Glasgow Coma Scale. Studies of CSF were performed on admission and after 3 to 6 days. In addition to standard CSF investigations, including cell count, cytologic findings, protein analysis, glucose and lactate levels, and microbiological tests, the concentration of glutamate in the CSF was measured by an enzymatic assay. RESULTS: At admission, both CSF cell count and concentration of glutamate correlated well with the severity of the disease. After treatment, glutamate concentrations decreased significantly to normal or only slightly elevated levels in 23 patients. However, in 7 patients glutamate levels remained markedly increased. In this group, clinical outcome was significantly worse than in the group of patients with low glutamate levels in the second CSF analysis. CONCLUSIONS: A prolonged increase of glutamate levels in the CSF may predict poor clinical outcome in patients with bacterial meningitis, possibly because of the sustained neurotoxic effects of this excitatory neurotransmitter.

Adolescent↗
PubMed1996

Transforming growth factor beta 1 is significantly elevated in plasma of patients suffering from renal cell carcinoma.

The levels of active and latent transforming growth factor beta 1 (aTGF-beta 1, ITGF-beta 1, respectively) in plasma samples were measured by enzyme-linked immunoabsorbent assay (ELISA). Samples were collected from patients suffering from renal cell carcinoma (RCC) before they underwent tumour resection. In all cases tested, the levels of latent TGF-beta 1 were much higher (n = 23, 41.0 +/- 13.9, range 19.3-78.1 ng/ml) than in healthy controls (n = 21, 3.8 +/- 2.9, range 0.6-9.9, P < < 0.0001), while active TGF-beta 1 did not differ that impressively (n = 38, 1.2 +/- 1.3, range 0.0-4.5 for RCC, n = 21, 0.1 +/- 0.2, range 0.0-1.1 in controls, P < 0.001). As for TGF-beta 1 production by proximal tubulus cells has been shown, it was speculated that these high TGF-beta 1 levels might be due to secretion by the tumour, which usually originates from proximal tubuli. Indeed, production of TGF-beta 1 was found in culture supernatants, and it was possible to show TGF-beta 1 mRNA expression in tumour samples. This TGF-beta 1 was predominantly secreted in the latent form. This is in contrast to data from other authors, who found TGF-beta 1 to be secreted mainly in the active form, but need not mean that it is inactive locally as the low pH encountered within tumours is in the range necessary for its activation. It is concluded that elevated latent TGF-beta 1 is common in RCC, is at least partially produced by the tumour and might be a cause for local immunosuppressive effects within the tumour.

Carcinoma, Renal Cell↗
PubMed1996

[Intensive care in acute ischemia].

Therapy of ischemic infarction has changed enormously during the last decade. This is due to an increase of pathophysiological knowledge on cerebrovascular disease, new diagnostic and intensive-care methods and success in thrombolytic therapy strategies; new neuroprotective drugs are on the way to be used on a routine base. The old fatalistic attitude towards treatment of stroke can nowadays not be justified. The success of stroke treatment is dependent on a fast and consequent therapeutic performing: patients with ischemic stroke who reach the hospital within six hours after onset of symptoms are candidates for thrombolysis. If certain inclusion criteria are fulfilled. Increasingly intracranial pressure is one of the major problems during the acute phase. Anti-edema treatment follows a stepwise scheme. In some selected cases we perform hemicraniectomy. Besides the routine intensive-care monitoring, further monitoring is necessary by evoked potentials, brain pressure probes and Doppler ultrasound.

Acute Disease↗
PubMed1996

[Reversible cerebral MRI findings in acute microangiopathic hemolytic anemia].

A case of acute microangiopathic hemolytic anemia in a 29-year-old primiparous patient is presented. Following an unsuspicuous pregnancy and uncomplicated delivery, the patient developed upper abdominal symptoms and transient psychopathologic abnormalities 2 days after delivery. Because of a series of generalized tonic-clonic seizures and respiratory distress she was admitted to the Neuro ICU. Focal neurological symptoms were absent, and CSF analysis was normal. Laboratory findings indicated hemolytic anemia with fragmented erythrocytes in smear specimens, thrombocytopenia, reticulocytosis, marked elevation of liver and pancreatic enzymes, and microhematuria. T2-weighted MR scans of the brain discluded multiple ischemic lesions of the cerebral white and gray matter, caudate nucleus and pons, displaying a hemodynamic pattern. Specific treatment included administration of corticosteroids, repeated plasmapheresis with substitution by fresh frozen plasma and antithrombin III. A control MR performed on the 3rd day of treatment demonstrated the absence of nearly all abnormal findings previously obtained. During a 3-week clinical course the patient showed full recovery, including normalization of hematologic and neuroradiologic findings. This case demonstrates ischemic cerebral lesions in acute microangiopathic hemolytic anemia to be potentially reversible if specific treatment is provided.

Adult↗
PubMed1995

Water molecules which apparently accept no hydrogen bonds are systematically involved in C-H...O interactions.

The hydrogen-bond acceptor functions are analyzed for 672 water molecules in crystal structures of hydrated small biological molecules. Of the 672 water molecules, 26 neither accept hydrogen bonds from O-H or N-H donors, nor coordinate to metal ions. As compensation, they satisfy their acceptor potential with up to four C-H.O hydrogen bonds. They are found in hydrated amino acids, purines and pyrimidines, and alkaloids, but not in carbohydrates, nucleosides, nucleotides and steroids. As for conventional hydrogen bonds, the preferred coordination geometry is tetrahedral. No example of a true non-accepting water molecule is found. A particularly strong C-H hydrogen-bond donor occurring in many biological molecules is C-H neighbouring protonated N.

Journal Article↗
PubMed1994

Crystal structure of beta-D-cellotetraose hemihydrate with implications for the structure of cellulose II.

The crystal structure of beta-D-cellotetraose shows the same molecule packing as cellulose II, with two antiparallel molecules in the unit cell: For cellulose II, the orientation of the C6-O6 bonds has been described as gauche-trans and trans-gauche, respectively, for the two antiparallel molecules, which otherwise have identical conformations. In contrast, in beta-D-cellotetraose all C6-O6 bonds are gauche-trans, but the conformations of the two antiparallel molecules are different. Energy minimization and molecular dynamics studies suggest that the structure of cellulose II should be reinvestigated in light of these findings.

Carbohydrate Conformation↗
PubMed1993

Crystal structures of cyclomaltoheptaose (beta-cyclodextrin) complexed with ethylene glycol.8.0H2O and glycerol.7.2H2O.

Single-crystal X-ray diffraction studies were carried out for the title compounds at room temperature. The crystal packings are of the cage-type and isomorphous to that of beta-cyclodextrin (beta CD) hydrate. In both crystal structures, disorder and extensive thermal vibrations of the complexed guest molecules are observed. In beta CD-ethylene glycol.8H2O, one ethylene glycol molecule (disordered over two discrete sites) and three water molecules (four discrete sites) are included in the beta CD cavity. Within the beta CD cavity, all oxygen sites (ordered and disordered) are in positions occupied by water molecules in beta CD.12H2O; this is only possible because the ethylene glycol molecule adopts the low-energy conformation with the O-C-C-O torsion angle approximately 60 degrees and an O...O separation of 2.9 A, in which its hydroxyl groups can directly substitute for two hydrogen-bonding water molecules. In beta CD-glycerol.7.2H2O, one glycerol molecule (disordered over two discrete sites) and two water molecules (two fully occupied sites) are included in the beta CD cavity. The general situation in both compounds parallels that found earlier in beta CD-ethanol.8H2O. It is assumed that the disorder is dynamic, i.e., associated with jumps between the partially occupied molecular sites.

Carbohydrate Sequence↗
PubMed1993

The ordered water cluster in vitamin B12 coenzyme at 15 K is stabilized by C-H...O hydrogen bonds.

The hydrogen-bonding interactions of the ordered water cluster in the pocket region of vitamin B(12) coenzyme at 15 K are analyzed from published atomic coordinates. Several of these water molecules accept C-H.O hydrogen bonds from the pocket wall, most of which have the function to complete tetrahedral hydrogen-bond coordination. This is the largest water assembly for which the stabilizing function of C-H.O interactions has been described.

Journal Article↗
PubMed1993

Determination, purification, and characterization of alpha-NADH.

alpha-NADH can be determined in the presence of high concentrations of beta-NADH using anion exchange HPLC combined with oxidation of beta-NADH by lactate dehydrogenase. The method is suited for the detection of a large number of impurities. Residual absorption is a poor measure of alpha-NADH. By combination of preparative anion exchange chromatography and reversed-phase HPLC, alpha-NADH can be prepared with 95-98% purity starting from beta-NADH. Commercially available preparations contain only 80-90% alpha-NADH. The anomerization kinetics of alpha- and beta-NADH has been investigated at pH 7.0 and 7.3 taking into account the irreversible conversion reactions of alpha- and beta-NADH. The H+ ion activity related anomerization rate constants kappa 1 (alpha to beta) and kappa 2 (beta to alpha) have been found to be 170 and 29 M-1 s-1, respectively, at pH 7.0 and 192 and 36 M-1 s-1, respectively, at pH 7.3. The equilibrium constants kappa 1 /kappa 2 are 5.8 and 5.3 at pH 7.0 and pH 7.3, respectively. Absorption and fluorescence properties of alpha-NADH preparations have been determined newly. At 25 degrees C, maximum absorption was found at 260.1 and 346.6 nm, whereas at 37 degrees C the wavelengths were 260.1 and 345.3 nm. Maximum fluorescence excitation was found at 348 nm, and maximum emission was at 453 nm.

Anions↗
PubMed1993

Cellular adaptation in migraineurs with chronic daily headache.

Ergotamine and analgesic misuse are now recognized as causes of chronic daily headache and the condition responds well to drug withdrawal with reduced headache frequency. In this study, we have investigated whether medication misuse is associated with an alteration in membrane transduction which is sensitive to drug withdrawal. This was carried out by assay of the thrombin-stimulated generation of inositol phosphates in platelets from 12 migraine patients with chronic daily headache and analgesic misuse, 7 migraine patients with chronic daily headache and ergotamine misuse and 7 control subjects. After drug withdrawal, a significant decrease in headache frequency was seen at one month in both patient groups. Withdrawal of analgesics produced a significant decrease in thrombin-stimulated inositol phosphate production at one month; this was further decreased a month later with a reduction in Bmax of 60% and no significant change in KD. A similar pattern was obtained in ergot misuse patients, with the KD value decreasing by 56% one month after drug withdrawal. These results provide evidence of an adaptation in transduction with misuse of analgesics and ergotamine which correlates with headache frequency.

Adult↗
PubMed1992

Crystalline beta-cyclodextrin.12H2O reversibly dehydrates to beta-cyclodextrin.10.5 H2O under ambient conditions.

In contact with mother liquor, crystalline beta-cyclodextrin (beta-CD) hydrate has composition approximately beta-CD.12H2O. If crystals are dried at ambient conditions (18 degrees C, approximately 50% humidity), the unit cell volume diminishes approximately 30 to 50 A3. X-ray structure analysis of a dry crystal (0.89 A resolution, 4617 data, R = 0.059) showed the composition beta-CD.10.5 H2O, with approximately 5.5 water molecules in the beta-CD cavity (7 partially and 2 fully occupied sites) and approximately 5.0 between the beta-CD molecules. The positions of the beta-CD host and of most of the hydration waters are conserved during dehydration, but the occupancies of the waters in the beta-CD cavity diminish. Dry crystals put into solvent re-hydrate to the original form. The mechanism of de- and re-hydration is not evident.

Crystallization↗
PubMed1992

A vibrating flexible chain in a molecular cage: crystal structure of the complex cyclomaltoheptaose (beta-cyclodextrin)-1,4-butanediol.6.25H2O.

A single crystal X-ray diffraction study of the title complex carried out at room temperature revealed space group P2(1), a = 21.199(12), b = 9.973(3), c = 15.271(8) A, beta = 110.87(3) degrees, V = 3017(3) A3, 4681 unique reflections with Fo greater than 1 sigma (Fo). The structure was refined to R = 0.069, resolution lambda/2sin theta max = 0.89 A. The crystal packing is of the cage type and is isomorphous to that of beta-cyclodextrin (beta CD) dodecahydrate. One 1,4-butanediol and approximately 1.25 water molecules are enclosed in each beta CD cavity. The hydroxyl groups of the 1,4-butanediol molecule are located at each end of the cavity and form hydrogen bonds with neighboring water and beta CD molecules. The flexible (CH2)4 moiety vibrates extensively in the central part of the cavity. Water molecules and hydroxyl groups are chelated between O-6 and O-5 of at least five glucose residues.

Butylene Glycols↗