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Biomedical subjects

W Steiner

Publications and source records attributed to W Steiner.

At least 37 records · Page 2Linked to original sources

Natural disasters and service delivery to individuals with severe mental illness--ice storm 1998.

OBJECTIVE: To review the literature on the responses of individuals with severe mental illness (SMI) to natural disasters, to describe the impact of the 1998 Ice Storm on a group of SMI patients, and to describe the steps taken at a Canadian university teaching hospital to ensure the ongoing provision of mental health services throughout the crisis. METHOD: Published articles describing the impact of natural disasters on SMI populations, as well as service provision to these patients, are reviewed. Service use at the Montreal General Hospital (MGH) Department of Psychiatry is described. A questionnaire about the impact of the ice storm was administered to a group of patients in an assertive community treatment program. RESULTS: Service use during this natural disaster was consistent with that described in the literature, in that these patients were no more likely to be admitted or to visit the emergency room during the crisis. Continuous mental health service delivery may have contributed to this positive outcome. This service delivery was provided by ensuring staff access to information, by securing the physical safety of both staff and patients, and by taking a flexible, outreach-oriented approach to service delivery. CONCLUSIONS: SMI patients who have ongoing access to psychiatric services in disaster situations tend to cope well. A flexible, proactive, assertive approach to service delivery during the crisis situation will help to ensure that needs for care will be met.

Adaptation, Psychological↗

Esterase and lipase activity in Jatropha curcas L. seeds.

Two new esterases (JEA and JEB) and a lipase (JL) were extracted from the seeds of Jatropha curas L. Lipase activity was only found during germination of the seeds and increased to a maximum after 4 days of germination. All enzymes were found to be most active in the alkaline range at around pH 8 and the purified (fractionated precipitation with ethanol and gel filtration) esterases were very stable at high temperatures. The molecular weight (SDS-PAGE) of both esterases was determined to be 21.6-23.5 kDa (JEA) and 30.2 kDa (JEB) and the isoelectric point was 5.7-6.1 for esterase JEA and 9.0 for esterase JEB. Most ions caused a negative influence on the activity of both esterases. Using p-nitrophenyl butyrate as a substrate JEA showed a K(m) of 0.02 mM and a v(max) of 0.26 micromol mg(-1) min(-1). Under the same conditions JEB showed a K(m) of 0.07 mM and a v(max) of 0.24 micromol mg(-1) min(-1). Both esterases hydrolyzed tributyrin, nitrophenyl esters up to a chain length of =C4 and naphtylesters up to a chain length =C6. In transesterification reactions, JL was found to be most active at very low water activities (0.2) and in high water activities, the lipase hydrolysed triglycerides into conversions above 80%. The lipase hydrolysed both short chain and long chain triglycerides at about the same rate but was inactive on alpha-methylbenzyl acetate. JL is a potentially useful biocatalyst in the hydrolysis of triglycerides in organic solvents.

Esterases↗

Spontaneous apoptosis in laryngeal squamous cell carcinoma is independent of bcl-2 and bax protein expression.

BACKGROUND: bcl-2 and bax genes are known to be involved in the control of apoptotic cell death, an important mechanism of growth regulation that influences the biologic behavior of tumors. The aim of the current study was to investigate the relationship of bcl-2 and bax expression to the rate of spontaneous apoptosis in laryngeal carcinomas, and to assess its relations to clinicopathologic features of tumors. METHODS: Immunohistochemical analyses for bcl-2 and bax were performed on paraffin embedded tissue sections from 134 primary laryngeal squamous cell carcinomas. To visualize apoptotic cells, the nick end labeling method was used. The proliferative activity of tumors was analyzed by determination of mitotic indices. RESULTS: bcl-2 immunoreactivity was positively correlated with tumor grade (P < 0.00001), high T category (P < 0.02), metastatic involvement of cervical lymph nodes (P < 0.003), and supraglottic or subglottic location of primary tumors (P < 0.00005). An inverse relation was found between bcl-2 and bax expression (P < 0.004). The frequency of spontaneous apoptosis was closely associated with mitotic activity (P < 0.0004) but appeared to be unrelated to protein levels of bcl-2 or bax as well as to bcl-2:bax ratios. CONCLUSIONS: The results of this study point to the significance of cell proliferation as a major determinant of the rate of spontaneous apoptosis in laryngeal carcinomas. The bcl-2:bax expression ratio obviously does not affect the incidence of apoptosis, but it may be considered as a marker of disease progression and poor prognosis.

Adult↗

Kinetic studies on the enzyme (S)-hydroxynitrile lyase from hevea brasiliensis using initial rate methods and progress curve analysis

(S)-Hydroxynitrile lyase (EC 4.1.2.39) from Hevea brasiliensis(rubber tree) catalyzes the reversible cleavage of cyanohydrins to aldehydes or ketones and prussic acid (HCN). Enzyme kinetics in both directions was studied on a model system with mandelonitrile, benzaldehyde, and HCN using two different methods-initial rate measurements and progress curve analysis. To discriminate between possible mechanisms with the initial rate method, product inhibition was studied. Benzaldehyde acts as a linear competitive inhibitor against mandelonitrile whereas HCN shows S-linear I-parabolic mixed-type inhibition. These results indicate an Ordered Uni Bi mechanism with the formation of a dead-end complex of enzyme, (S)-mandelonitrile and HCN. Prussic acid is the first product released from the enzyme followed by benzaldehyde. For progress curve analysis, a kinetic model of an Ordered Uni Bi mechanism including a dead-end complex, enzyme inactivation, and the chemical parallel reaction was set up, which described the experimental values very well. From the reaction rates obtained the kinetic constants were calculated and compared with the ones obtained from the initial rate method. Good agreement could be achieved between the two methods supporting the suggested mechanism. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗

Incompatibility and pollen competition in Alnus glutinosa: Evidence from pollination experiments.

Different types of incompatibility systems were found to operate simultaneously in Alnus glutinosa in the course of numerous pollination experiments, including self-pollination and pollination with controlled pollen mixtures. Isozyme genetic markers were used to identify the pollen parent of each offspring from the mixed pollination experiments, thus allowing specification of the fertilization success of each pollen parent. In a first step, these results were compared with observations on in vitro pollen germination experiments. This comparison allows for exploration of the explanatory value of different germination media as models of germination conditions on stigmas. In most cases, the data suggest that the in vitro germination conditions resemble the fertilization conditions in vivo, at least in the sense that they favor the same pollen parents. By providing a generic and operable definition of the two basic types of incompatibility, eliminating (inability to fertilize ovules) and cryptic (resulting in lowered fertilization success of a pollen parent under competition), evidence was detected for the existence of both types of incompatibility in Alnus glutinosa, where eliminating incompatibility occurred as self-incompatibility only. However, since this incompatibility seems to act primarily via pollen elimination, seed production is not likely to be negatively affected in natural populations, even for comparatively large amounts of self-pollination.

Journal Article↗

The cytoplasmic domain of FtsK protein is required for resolution of chromosome dimers.

Chromosome dimers, formed by homologous recombination between sister chromosomes, normally require cell division to be resolved into monomers by site-specific recombination at the dif locus of Escherichia coli. We report here that it is not in fact cell division per se that is required for dimer resolution but the action of the cytoplasmic domain of FtsK, which is a bifunctional protein required both for cell division and for chromosome partition.

Binding Sites↗

Proton-nuclear magnetic resonance analyses of the substrate specificity of a beta-ketolase from Pseudomonas putida, acetopyruvate hydrolase.

A revised purification of acetopyruvate hydrolase from orcinol-grown Pseudomonas putida ORC is described. This carbon-carbon bond hydrolase, which is the last inducible enzyme of the orcinol catabolic pathway, is monomeric with a molecular size of approximately 38 kDa; it hydrolyzes acetopyruvate to equimolar quantities of acetate and pyruvate. We have previously described the aqueous-solution structures of acetopyruvate at pH 7.5 and several synthesized analogues by (1)H-nuclear magnetic resonance (NMR)-Fourier transform (FT) experiments. Three (1)H signals (2.2 to 2.4 ppm) of the methyl group are assigned unambiguously to the carboxylate anions of 2,4-diketo, 2-enol-4-keto, and 2-hydrate-4-keto forms (40:50:10). A (1)H-NMR assay for acetopyruvate hydrolase was used to study the kinetics and stoichiometries of reactions within a single reaction mixture (0.7 ml) by monitoring the three methyl-group signals of acetopyruvate and of the products acetate and pyruvate. Examination of 4-tert-butyl-2,4-diketobutanoate hydrolysis by the same method allowed the conclusion that it is the carboxylate 2-enol form(s) or carbanion(s) that is the actual substrate(s) of hydrolysis. Substrate analogues of 2,4-diketobutanoate with 4-phenyl or 4-benzyl groups are very poor substrates for the enzyme, whereas the 4-cyclohexyl analogue is readily hydrolyzed. In aqueous solution, the arene analogues do not form a stable 2-enol structure but exist principally as a delocalized pi-electron system in conjugation with the aromatic ring. The effects of several divalent metal ions on solution structures were studied, and a tentative conclusion that the enol forms are coordinated to Mg(2+) bound to the enzyme was made. (1)H-(2)H exchange reactions showed the complete, fast equilibration of (2)H into the C-3 of acetopyruvate chemically; this accounts for the appearance of (2)H in the product pyruvate. The C-3 of the product pyruvate was similarly labelled, but this exchange was only enzyme catalyzed; the methyl group of acetate did not undergo an exchange reaction. The unexpected preference for bulky 4-alkyl-group analogues is discussed in an evolutionary context for carbon-carbon bond hydrolases. Routine one-dimensional (1)H-NMR in normal (1)H(2)O is a new method for rapid, noninvasive assays of enzymic activities to obtain the kinetics and stoichiometries of reactions in single reaction mixtures. Assessments of the solution structures of both substrates and products are also shown.

Bacterial Proteins↗

Thermophilic xylanase from Thermomyces lanuginosus: high-resolution X-ray structure and modeling studies.

The crystal structure of the thermostable xylanase from Thermomyces lanuginosus was determined by single-crystal X-ray diffraction. The protein crystallizes in space group P21, a = 40.96(4) A, b = 52. 57(5) A, c = 50.47 (5) A, beta = 100.43(5) degrees, Z = 2. Diffraction data were collected at room temperature for a resolution range of 25-1.55 A, and the structure was solved by molecular replacement with the coordinates of xylanase II from Trichoderma reesei as a search model and refined to a crystallographic R-factor of 0.155 for all observed reflections. The enzyme belongs to the family 11 of glycosyl hydrolases [Henrissat, B., and Bairoch, A. (1993) Biochem. J. 293, 781-788]. pKa calculations were performed to assess the protonation state of residues relevant for catalysis and enzyme stability, and a heptaxylan was fitted into the active-site groove by homology modeling, using the published crystal structure of a complex between the Bacillus circulans xylanase and a xylotetraose. Molecular dynamics indicated the central three sugar rings to be tightly bound, whereas the peripheral ones can assume different orientations and conformations, suggesting that the enzyme might also accept xylan chains which are branched at these positions. The reasons for the thermostability of the T. lanuginosus xylanase were analyzed by comparing its crystal structure with known structures of mesophilic family 11 xylanases. It appears that the thermostability is due to the presence of an extra disulfide bridge, as well as to an increase in the density of charged residues throughout the protein.

Amino Acid Sequence↗

Transoral laser surgery of supraglottic cancer: follow-up of 141 patients.

OBJECTIVE: To determine the role of transoral laser resection of supraglottic carcinomas. DESIGN: Retrospective unicenter study of the oncologic results of transoral carbon dioxide laser microsurgery for supraglottic carcinomas performed between February 1979 and December 1993. Median follow-up was 37 months. SETTING: University hospital academic tertiary referral center. PATIENTS: We reviewed the medical records of 141 patients (a consecutive sample of 131 men and 10 women; mean age, 60 years) with histologically proven supraglottic carcinomas undergoing transoral laser surgery, possibly in combination with neck dissection or radiotherapy. Stage distribution of patients was as follows: stage I, 23.4%; stage II, 25.5%; stage III, 16.3%; and stage IV, 34.8% (according to the Union Internationale Contre le Cancer staging system). MAIN OUTCOME MEASURES: Recurrence-free survival rates and local and regional recurrence rates. RESULTS: Five-year recurrence-free survival rates were as follows: the whole case load, 65.7%; stage I, 85.0%; stage II, 62.6%; stage III, 74.2%; and stage IV, 45.3%, according to the Union Internationale Contre le Cancer staging system. The local and regional recurrence rates were 16.3% and 9.9%, respectively. CONCLUSIONS: The oncologic results of transoral carbon dioxide laser surgery are satisfying if clean surgical margins (R0 resection) can be reached. In patients in whom tumor-free margins are not achieved (R1 and R2 resection) and transoral revision is not possible, transcervical procedures (partial or total laryngectomy) should be performed. The indication for transoral supraglottic laryngectomy in T3 lesions should be considered with restraint.

Adult↗

Structure of the xylanase from Penicillium simplicissimum.

Despite its relatively low pH and temperature optimum, the xylanase from Penicillium simplicissimum performs exceedingly well under conditions of paper bleaching. We have purified and characterized this enzyme, which belongs to family 10 of glycosyl hydrolases. Its gene was cloned, and the sequence of the protein was deduced from the nucleotide sequence. The xylanase was crystallized from ammonium sulfate at pH 8.4, and X-ray data were collected at cryo-temperature to a crystallographic resolution of 1.75 A. The crystal structure was solved by molecular replacement using the catalytic domain of the Clostridium thermocellum xylanase as a search model, and refined to a residual of R = 20% (R(free) = 23%) for data between 10 and 1.75 A. The xylanase folds in an (alpha/beta)8 barrel (TIM-barrel), with additional helices and loops arranged at the "top" forming the active site cleft. In its overall shape, the P. simplicissimum xylanase structure is similar to other family 10 xylanases, but its active site cleft is much shallower and wider. This probably accounts for the differences in catalysis and in the mode of action of this enzyme. Three glycerol molecules were observed to bind within the active site groove, one of which interacts directly with the catalytic glutamate residues. It appears that they occupy putative xylose binding subsites.

Amino Acid Sequence↗

[Tracheobronchoscopy and esophagoscopy in otorhinolaryngology. An assessment of current status].

Its is the task of each medical specialty to develop guidelines for diagnosis and therapies. Examinations done by several specialties should follow a common consensus. A randomized survey at 70 German ENT departments investigated the current position of tracheobronchoscopy and esophagoscopy at each institution. Sixty questionnaires were evaluable. Altogether 8,295 tracheobronchoscopies and 10,404 esophagoscopies were performed. Thirty-six percent of all tracheobronchoscopies and 6% of all esophagoscopies were done with a flexible system. Approximately 58% of all tracheobronchoscopies and 55% of all esophagoscopies were performed for tumor staging. Complications during tracheobronchoscopy occurred in 0.8% of cases and in 0.58% of the esophagoscopies. Using these data an interdisciplinary quality assurance concept was developed for tracheobronchoscopy and esophagoscopy. Current experience has shown that a otolaryngologists in Germany mainly perform rigid tracheobronchoscopy and esophagoscopy. Although endoscopy is mostly done in cases with varied anatomic structures, complications are very rare and comparable to flexible techniques. Greater experience with flexible systems also is to be encouraged in ENT departments.

Bronchoscopes↗

Carbon dioxide laser microsurgery for early supraglottic carcinoma.

Forty-eight untreated patients with early supraglottic carcinoma (12 patients stage I and 36 patients stage II) had primary carbon dioxide laser microsurgery between 1979 and 1994 with the intent of complete tumor removal with preservation of functionally important structures of the larynx. Ninety-six percent of the patients were treated exclusively by surgery; 4% had laser microsurgery and postoperative radiotherapy. With a median follow-up of 55 months, the 5-year local control rate with the first treatment was 100% for pT1 cases and 89% for pT2 cases. The ultimate local control rate with voice preservation, including patients successfully salvaged after a local recurrence, was 97% for pT2 carcinomas. Five (10%) patients died of tumor (TNM)-related deaths. The 3-year recurrence-free rate and 3-year overall survival rate (Kaplan-Meier) were 87% and 85%; the 5-year recurrence-free rate and 5-year overall survival rate were 83% and 76%, respectively. The results achieved with transoral laser microsurgery in early supraglottic carcinoma are comparable to those of open supraglottic laryngectomy with respect to local control and survival. The functional results are superior, since clinically relevant aspiration did not occur.

Adult↗

Oligonucleotide inhibitors of human thrombin that bind distinct epitopes.

Thrombin, a multifunctional serine protease, recognizes multiple macromolecular substrates and plays a key role in both procoagulant and anticoagulant functions. The substrate specificity of thrombin involves two electropositive surfaces, the fibrinogen-recognition and heparin-binding exosites. The SELEX process is a powerful combinatorial methodology for identifying high-affinity oligonucleotide ligands to any desired target. The SELEX process has been used to isolate single-stranded DNA ligands to human thrombin. Here, a 29-nucleotide single-stranded DNA ligand to human thrombin, designated 60-18[29], with a Kd of approximately 0.5 nM is described. DNA 60-18[29] inhibits thrombin-catalyzed fibrin clot formation in vitro. Previously described DNA ligands bind the fibrinogen-recognition exosite, while competition and photocrosslinking experiments indicate that the DNA ligand 60-18[29] binds the heparin-binding exosite. DNA 60-18[29] is a quadruplex/duplex with a 15-nucleotide "core" sequence that has striking similarity to previously described DNA ligands to thrombin, but binds with 20 to 50-fold higher affinity. The 15-nucleotide core sequence has eight highly conserved guanine residues and forms a G-quadruplex structure. A single nucleotide within the G-quadruplex structure can direct the DNA to a distinct epitope. Additional sequence information in the duplex regions of ligand 60-18[29] contribute to greater stability and affinity of binding to thrombin. A low-resolution model for the interaction of DNA 60-18[29] to human thrombin has been proposed.

Aptamers, Nucleotide↗

[Radiologic interventions in anastomosis complications after lung transplantation].

PURPOSE: Bronchial and arterial anastomotic stenoses are major complications after lung transplantation. Interventional techniques provide a definitive cure in certain cases. MATERIAL AND METHODS: Three out of four patients had ischemia-related stenoses of the bronchial anastomoses postoperatively; one patient developed malacia of the bronchus main stem 1 year after transplantation. Four patients has stenoses of the arterial anastomoses, which resulted in hemodynamic instability and reduced perfusion of the graft. RESULTS: Stent implantation in the bronchial anastomoses (n = 3) and in the main stem (n = 1) improved ventilation and oxygen saturation in all patients. The stents were incorporated by mucosal overgrowth, as demonstrated by endoscopy, as early as 6 weeks after implantation. Balloon dilatation (n = 3) and stent implantation (n = 1) were successfully performed in 4 patients with stenoses of the arterial anastomoses. The mean transstenotic pressure gradient of 9.5 mm Hg was reduced to 2.2 mm Hg after angioplasty. Lung perfusion shifted towards the grafts, as shown by 99mTc perfusion scans. CONCLUSION: The minimally invasive techniques of interventional radiology are very effective in the treatment of anastomotic complications after lung transplantation and may avoid surgery in certain cases.

Adult↗

Cancellous bone structure in the growing and aging lumbar spine in a historic Nubian population.

There is abundant data on cancellous bone in the aging human spine, but little relating to the growing vertebral cancellous bone in childhood an adolescence. The purpose of this study was to map vertebral cancellous bone in a growth and age series of historic skeletal samples and to make comparisons with data published on recent material. Lumbar vertebral bodies were collected from 65 skeletons (0-60 years) from a medieval Nubian population. Ethnohistoric information was collected to interpret conditions that might have influenced bone structure and metabolism. The cancellous bone was studied three dimensionally, using stereophotography and scanning electron microscopy and morphometrically by performing a semiautomatic structural analysis on digitized backscattered electron images of polymethacrylate-embedded material. The cancellous bone structure in the children consisted mainly of a densely packed, uniform network of small rodlike trabeculae. The greatest bone volume fraction with small, more platelike trabeculae was observed during adolescence. In young adults, larger platelike trabeculae were present in the central zone and smaller trabeculae in the superior and inferior zones, as described for modern skeletal material. Structural changes associated with aging were observed much sooner than in modern man. by the estimated age of approximately 50-60 years, the predominant architectural elements were slender rarified rods in both sexes. The ethnohistorical data suggest that this was essentially a black African population of physically active peasants, not likely to suffer Vitamin D insufficiency or deficient calcium intake. Thus an earlier onset of the biological age changes in cancellous bone found in modern populations was probably relevant.

Adult↗

Reinforcement of genetic coherence: a single-locus model.

Genetic coherence and genetic separation are the outcome of evolutionary mechanisms which maintain genetic variation within populations through recombination on the one hand, and which divide this variation via speciation between reproductively (recombinatorically) more or less isolated populations on the other. While mechanisms of speciation have received considerable attention in biology, their counterpart, mechanisms of genetic coherence, are addressed only implicitly, if at all. Usually, genetic coherence is intuitively associated with the forces maintaining genetic polymorphisms and thus potential for flexible adaptational reaction of populations. However, so far no models seem to exist which explain the evolution of genetic coherence as the natural counterpart of genetic separation or speciation. In this paper a single-locus model is analyzed, in which a mutant allele is introduced into a resident stable diallelic polymorphism, and where this allele is equivalent to one of the resident alleles in all respects with the exception of mating relations. The conditions for replacement of the resident allele by its selectively equivalent mutant are obtained with reference to the associated mating relations. It turned out that for heterozygote advantage the mutant replaces the selectively equivalent resident allele if it increases the mating preferences for carriers of other alleles. The evolution of lower such preferences requires heterozygote inferiority, which confirms the Wallace effect of speciation (by reinforcement). It is argued that this observation suggests that non-selective constituents of the mating system form the section of the genetic system that is responsible for moderating the genetic load implied by adapting selection while simultaneously securing the adaptational potential embodied in the resident allelic variation. Mating systems thus serve the preservation of adaptability.

Adaptation, Physiological↗

Screening of European coffee final products for occurrence of ochratoxin A (OTA).

Samples (633) of final coffee products were drawn from the markets of different European countries relative to the market share of each product type and brand. These samples were analysed in a cooperative action with nine different laboratories. With low limits of detection (mean detection limit approximately 0.5 ng/g) no OTA was found in over half of the samples (334 negatives). In the remaining samples occurrence of OTA at a rather low level was seen. Only four samples (all instants) exceeded a level of 10 ng/g, whereas for both instants, and roast and grounds (R & G), over three-quarters of the samples were in the range from nondetectable to 1 ng/g. The overall mean for all R & Gs was 0.8 ng/g and for all instant 1.3 ng/g (for samples in which no OTA was detected, half of the detection limit was included in this calculation). In the brewing methods frequently used in Europe the OTA is essentially fully extracted. Consumption of four cups of coffee per day (approximately 24 g R & G or approximately 8 g instant coffee) contributes on average 19 or 10 ng/day respectively. Four cups/day is above the per caput consumption level in most European contries. Compared with the Provisional Tolerable Weekly Intake (PTWI) recently set by the Joint FAO/WHO Expert Committee on Food Additives at 100 ng/kg bodyweight/week, consumption of 28 cups/week contributes up to 2% to the PTWI.

Carcinogens↗