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Biomedical subjects

M Groth

Publications and source records attributed to M Groth.

At least 19 recordsLinked to original sources
PubMed2004

Fungal polysaccharopeptide inhibits tumor angiogenesis and tumor growth in mice.

Angiogenesis is crucial to tumor growth and metastasis, and interruption of this process is a prime avenue for therapeutic intervention of tumor proliferation. The present study has made use of the S180 tumor-bearing mouse model to investigate the polysaccharopeptide, PSP, isolated from the edible mushroom Coriolus versicolor, a herbal medicine known for its anti-angiogenesis properties. Quantitative analysis of microcorrosion casting of the tumor tissue showed more angiogenic features such as dense sinusoids and hot spots, in control (untreated) than in PSP-treated animals. Immunostaining of tumor tissues with antibody against the endothelial cell marker (Factor VIII) demonstrated a positive correlation in that both the vascular density and tumor weight were lower in mice treated with PSP. Morphometric analysis of corrosion casts revealed that, even though the total amount of new vessel production was reduced, the basic tumor type-specific vascular architecture was retained. However, the expression of vascular endothelial cell growth factor (VEGF) in these tumors was suppressed. In conclusion, anti-angiogenesis should be one of the pathways through which PSP mediated its anti-tumor activity.

Administration, Oral↗
PubMed2004

Suppression of large edge-localized modes in high-confinement DIII-D plasmas with a stochastic magnetic boundary.

A stochastic magnetic boundary, produced by an applied edge resonant magnetic perturbation, is used to suppress most large edge-localized modes (ELMs) in high confinement (H-mode) plasmas. The resulting H mode displays rapid, small oscillations with a bursty character modulated by a coherent 130 Hz envelope. The H mode transport barrier and core confinement are unaffected by the stochastic boundary, despite a threefold drop in the toroidal rotation. These results demonstrate that stochastic boundaries are compatible with H modes and may be attractive for ELM control in next-step fusion tokamaks.

Journal Article↗
PubMed2001

Influence of solvents and leucine configuration at position 5 on tryptophan fluorescence in cyclic enkephalin analogues.

The fluorescence decay of tryptophan is a sensitive indicator of its local environment within a peptide or protein. In this study we carried out fluorescence measurements of the tryptophan residue of cyclic enkephalin analogues of a general formula X-c[D-Dab(2)-Gly(3)-Trp(4)-Y(5)] where X = Cbz or H and Y = D- or L-Leu, in four solvents [water, methanol, acetonitrile, and dimethyl sulfoxide (DMSO)]. An analysis of the tryptophan fluorescence decays using a discrete-exponential model indicates that tryptophan fluorescence decay can be described by a double exponential function in all solvents studied. Lifetime distribution analysis yields a bimodal distribution in protic solvents (water and methanol), whereas an asymmetric, unimodal distribution in an aprotic solvent (DMSO) and uni- or bimodal distributions in acetonitrile solution, depending on leucine configuration. The data are interpreted in terms of the rotamer model, in which the modality and the relative proportions of the lifetime components are related to the population distribution of tryptophan chi(1) rotamers about the C(alpha)--C(beta) bond. The chirality of the Leu(5) residue and solvent properties affect the local environment of the tryptophan residue and therefore influence the distribution of side-chain rotamers. These results are consistent with the results of theoretical conformational calculations.

Enkephalins↗
PubMed2001

Determination of conformational equilibrium of peptides in solution by NMR spectroscopy and theoretical conformational analysis: application to the calibration of mean-field solvation models.

Peptides occur in solution as ensembles of conformations rather than in a fixed conformation. The existing energy functions are usually inadequate to predict the conformational equilibrium in solution, because of failure to account properly for solvation, if the solvent is not considered explicitly (which is usually prohibitively expensive). NMR data are therefore widely incorporated into theoretical conformational analysis. Because of conformational flexibility, restrained molecular dynamics (with restraints derived from NMR data), which is usually applied to determine protein conformation is of limited use in the case of peptides. Instead, (a) the restraints are averaged within predefined time windows during molecular dynamics (MD) simulations (time averaging), (b) multiple-copy MD simulations are carried out and the restraints are averaged over the copies (ensemble averaging), or (c) a representative ensemble of sterically feasible conformations is generated and the weights of the conformations are then fitted so that the computed average observables match the experimental data (weight fitting). All these approaches are briefly discussed in this article. If an adequate force field is used, conformations with large statistical weights obtained from the weight-fitting procedure should also have low energies, which can be implemented in force field calibration. Such a procedure is particularly attractive regarding the parameterization of the solvation energy in nonaqueous solvents, e.g., dimethyl sulfoxide, for which thermodynamic solvation data are scarce. A method for calibration of solvation parameters in dimethyl sulfoxide, which is based on this principle was recently proposed by C. Baysal and H. Meirovitch (Journal of the American Chemical Society, 1998, Vol. 120, pp. 800--812), in which the energy gap between the conformations compatible with NMR data and the alternative conformations is maximized. In this work we propose an alternative method based on the principle that the best-fitting statistical weights of conformations should match the Boltzmann weights computed with the force field applied. Preliminary results obtained using three test peptides of varying conformational mobility: H-Ser(1)-Pro(2)-Lys(3)-Leu(4)-OH, Ac-Tyr(1)-D-Phe(2)-Ser(3)-Pro(4)-Lys(5)-Leu(6)-NH(2), and cyclo(Tyr(1)-D-Phe(2)-Ser(3)-Pro(4)-Lys(5)-Leu(6)) are presented.

Amino Acid Sequence↗
PubMed2001

Influence of solvent and configuration of residues at positions 2 and 3 on distance and mobility of pharmacophore groups at positions 1 and 4 in cyclic enkephalin analogues.

The analgesic activity of opioid peptides is mainly connected with their affinity and selectivity for the mu-receptors. The biological activity of cyclic opioid analogues depends on mutual orientation and conformational freedom of aromatic pharmacophore groups at positions 1 and 4. The distance and distance distributions between chromophores at positions 1 [Phe(p-NO(2)), p-nitrophenylalanine] and 4 [Nal, beta-(2-naphthyl)alanine], which constitute an energy donor-acceptor pair, were calculated based on measured fluorescence intensity decays of a donor (Nal). The influence of the solvent and configuration of the residues at position 2 and 3 on donor-acceptor distance distribution and mobility of pharmacophore groups at position 1 and 4 in cyclic enkephalin analogues are discussed.

Enkephalins↗
PubMed2001

Fluorescence decay time distribution analysis of cyclic enkephalin analogues; influence of solvent and Leu configuration in position 5 on conformation.

Lifetime distribution analysis were performed to study the influence of Leu configuration in position 5 on changes of the peptide chain of cyclic analogues of enkephalins containing a fluorescence donor and acceptor in different solvents. The configuration change of Leu5 in all the analogues of enkephalins studied which contain donor-acceptor pairs has no apparent influence on Trp lifetime distributions. In contrast, there is a significant solvent effect on the shape of lifetime distribution.

Enkephalins↗
PubMed2000

A systematic review of socio-economic differences in food habits in Europe: consumption of fruit and vegetables.

OBJECTIVE: To evaluate the differences in the consumption of fruit and vegetables between groups with different socio-economic status (SES) in the adult population of European countries. DESIGN: A systematic review of published and unpublished surveys of food habits conducted between 1985 and 1999 in 15 European countries. Educational level and occupational status were used as indicators of SES. A pooled estimate of the mean difference between the highest and the lowest level of education and occupation was calculated separately for men and women, using DerSimonian and Laird's random effects model. SETTING: The inclusion criteria of studies were: use of a validated method for assessing intake at the individual level; selection of a nationwide sample or a representative sample of a region; and providing the mean and standard deviation of overall fruit and vegetable consumption for each level of education or occupation, and separately for men and women. SUBJECTS: Participants in the individual surveys had to be adults (18-85 y). RESULTS: Eleven studies from seven countries met the criteria for being included in the meta-analysis. A higher SES was associated with a greater consumption of both fruit and vegetables. The pooled estimate of the difference in the intake of fruit was 24.3 g/person/day (95% confidence interval (CI) 14.0-34.7) between men in the highest level of education and those in the lowest level of education. Similarly, this difference was 33.6 g/person/day for women (95% CI 22.5-44.8). The differences regarding vegetables were 17.0 g/person/day (95% CI 8.6-25.5) for men and 13.4 g/person/day (95% CI 7.1-19.7) for women. The results were in the same direction when occupation instead of education was used as an indicator of SES. CONCLUSIONS: Although we cannot exclude over-reporting of intake by those with highest SES, it is unlikely that this potential bias could fully explain the differences we have found. Our results suggest that an unhealthier nutrition pattern may exist among adults belonging to lower socio-economic levels in Europe. SPONSORSHIP: The present study was supported by the European Union's FAIR programme (FAIR-97-3096).

Adolescent↗
PubMed1999

Maximum entropy approach to the determination of solution conformation of flexible polypeptides by global conformational analysis and NMR spectroscopy--application to DNS1-c-[D-A2,bu2,Trp4,Leu5]enkephalin and DNS1-c-[D-A2bu2,Trp4,D-Leu5]enkephalin.

A method is proposed to determine the conformational equilibrium of flexible polypeptides in solution, using the data provided by NMR spectroscopy and theoretical conformational calculations. The algorithm consists of the following three steps: (i) search of the conformational space in order to find conformations with reasonably low energy; (ii) simulation of the NOE spectrum and vicinal coupling constants for each of the low energy conformations; and (iii) determining the statistical weights of the conformations, by means of the maximum-entropy method, in order to obtain the best fit of the averaged NOE intensities and coupling constants to the experimental quantities. The method has been applied to two cyclic enkephalin analogs: DNS1-c-[D-A2bu2,Trp4,Leu5]enkephalin (ENKL) and DNS1-c-[D-A2bu2,Trp4,D-Leu5]enkephalin (ENKD). NMR measurements were carried out in deuterated dimethyl sulfoxide. Two techniques were used in conformational search: the electrostatically driven Monte Carlo method (EDMC), which results in extensive search of the conformational space, but gives only energy minima, and the molecular dynamics method (MD), which results in a more accurate, but also more confined search. In the case of EDMC calculations, conformational energy was evaluated using the ECEPP/3 force field augmented with the SRFOPT solvation-shell model, while in the case of MD the AMBER force field was used with explicit solvent molecules. Both searches and subsequent fitting of conformational weights to NMR data resulted in similar conformations of the cyclic part of the peptides studied. For both ENKL and ENKD a common feature of the low-energy solution conformations is the presence of a type II' or type IV beta-turn at residues 3 and 4; the ECEPP/3 force field also gives a remarkable content of type III beta-turn. These beta-turns are tighter in the case of ENKL, which is reflected in different distributions of the D-A2bu(N gamma H)...D-A2bu(CO) and D-A2bu(N gamma H)...Gly3(CO) hydrogen-bonding distances, indicating that the D-A2bu(N gamma H) amide proton is more shielded from the solvent than in the case of ENKD. This finding conforms with the results of temperature coefficient data of the D-A2bu(N gamma H) proton. It has also been found that direct (MD) or Boltzmann (EDMC) averages of the observables do not exactly conform with the measured values, even when explicit solvent molecules are included. This suggests that improving force-field parameters might be necessary in order to obtain reliable conformational ensembles in computer simulations, without the aid of experimental data.

Algorithms↗
PubMed1999

Fluorescence decay time distribution analysis of cyclic enkephalin analogues. Influence of the solvents and configuration of amino acids in position 2 and 3 on changes in conformation.

The lifetime distribution calculations were applied to study the influence of configuration of amino-acid residues in positions 2 and 3 on changes in conformation of the peptide chain of cyclic analogues of enkephalins containing a fluorescence energy donor and acceptor in different solvents. In all the solvents studied the lifetime distributions were bimodal. This testified to the presence of two families of conformations. In this paper the relationship between the population of each conformation and configuration of the residues in position 2 and 3, and the solvent used is discussed.

Amino Acid Sequence↗
PubMed1997

Design of a knowledge-based force field for off-lattice simulations of protein structure.

Prediction of protein structure from amino-acid sequence still continues to be an unsolved problem of theoretical molecular biology. One approach to solve it is to construct an appropriate (free) energy function that recognizes the native structures of some selected proteins (whose native structures are known) as the ones distinctively lowest in (free) energy and then to carry out a search of the lowest-energy structure of a new protein. In order to reduce the complexity of the problem and the cost of energy evaluation, the so-called united-residue representation of the polypeptide chain is often applied, in which each amino-acid residue is represented by only a few interaction sites. Once the global energy minimum of the simplified chain has been found, the all-atom structure can easily and reliably be constructed. The search of the lowest-energy structure is usually carried out by means of Monte Carlo methods, though use of more efficient global-optimization methods, especially those of deformation of original energy surface is potentially promising. Monte Carlo search of the conformational space can be accelerated greatly, if the chain is superposed on a discrete lattice (the on-lattice approach). On the other hand, the on-lattice approach prohibits the use of many efficient global-optimization methods, because they require both energy and its space derivatives. The on-lattice methods in which the chain is embedded in the continuous 3D space are, therefore, also worth developing. In this paper we summarize the work on the design and implementation of an off-lattice united-residue force field that is underway in our group, in cooperation with Professor HA. Scheraga of Cornell University, U.S.A.

Models, Molecular↗
PubMed1995

Chronic hemoptysis: an unusual manifestation of fungal sinusitis.

A woman with chronic hemoptysis as her only complaint had extensive testing and did not respond to antibiotic therapy. Radiologic examination of the sinuses identified a mass which, on surgical exploration, was found to be the result of a fungus, Pseudallescheria boydii. Although this fungus is known to be a cause of epistaxis, this is the first instance in which it has been reported to cause hemoptysis.

Adult↗
PubMed1993

Effect of recombinant tissue plasminogen activator on clot lysis and ventricular dilatation in the treatment of severe intraventricular haemorrhage.

Twelve patients with severe intraventricular haemorrhage (IVH) underwent intraventricular thrombolysis with recombinant tissue plasminogen activator (rtPA). External ventricular drainage was performed in all patients within 24 hours of haemorrhage. Fibrinolytic therapy was started within 24 hours from the onset of symptoms in ten cases, and in two further cases after 48 hours and 5 days, respectively. Two to 5 mg of rtPA were injected via the ventricular catheter into one or both lateral ventricles. The injection was repeated at intervals ranging from 6 to 24 hours until CT scans demonstrated a substantial reduction of intraventricular blood. The total rtPA doses per patient ranged from 3 to 31 mg. CT scans showed a marked reduction of intraventricular blood and normalization of ventricular size within 24 to 48 hours from the beginning of the fibrinolytic therapy. Rapid reduction of elevated intracranial pressure by continuous diversion of cerebrospinal fluid could be achieved in all patients, because the ventricular catheters never became obstructed by clotted blood during the fibrinolytic therapy. During the period of treatment, the level of consciousness, as classified according to the Glasgow Coma Scale, improved from a mean value of 7 to 12. One fatal case of meningitis most probably due to the ventriculostomy was the only complication related to the treatment. This method of treatment might improve the prognosis in patients in whom a large intraventricular haematoma volume, ventricular dilatation, and impaired cerebrospinal fluid circulation are major determinants for the outcome.

Aged↗
PubMed1991

[The whiplash injury. An overlooked and casually treated syndrome].

The whiplash trauma is defined as hyperextension followed by hyperflexion of the cervical spine or the reverse. The lesion occurs mainly in the occupants of a motor vehicle into which another vehicle collides from behind. Even when there is no radiographic evidence of injury, considerable lesions of the soft tissues may, nevertheless, be present. Review of the literature and the present authors' investigations reveal that up to 80% of the patients have chronic symptoms and 10% of these are severe enough to cause incapacity. The therapeutic regimen has not been well investigated but, at present, intermittent cooling and support by a collar for a few days followed by rapid mobilizing and exercises within the limit of pain are recommended.

Adolescent↗
PubMed1989

Occupational lung function impairment in never-smoking Danish welders.

In order to study the effect of welding fumes on lung function, 74 high-exposed welders and 31 age-matched electricians were examined in 1982. None had ever smoked tobacco or been exposed to known or potentially noxious agents to the lungs. A significant difference was found between the welders and the control group in vital capacity, total lung capacity, forced expiratory volume in one second, peak expiratory flow rate, maximal expiratory flow rate at 75% of vital capacity, diffusion capacity and slope of the alveolar plateau. The lungs of the welders were physiologically 10-15 years older than those of the control group. Thirty percent of the welders had a well defined respiratory disease. Their lung function impairment was predominantly obstructive (16 persons), but restrictive patterns were also seen (6 persons).

Adult↗
PubMed1989

Respiratory symptoms in Danish welders.

In order to study the effect of welding fumes on respiratory symptoms a cross sectional study was performed in 1982 among 2,660 welders, primarily shipyard welders, compared with a control group of 881 electricians. Only workers more than 34 years of age and in work at the time of the study were selected. Information about respiratory symptoms (using standardized BMRC questions) and exposure was obtained through a self-administered questionnaire. Seventy-four never-smoking welders and 31 never-smoking controls were selected for detailed clinical interviews and extended lung function tests. This article presents the results of the questionnaire study. The welders showed a significantly higher prevalence of chronic bronchitis: 21% versus 9% in the control group (p less than 0.01). The difference could neither be explained by differences in age or smoking habits nor by exposure to other air polluting substances. Other symptoms from the lower and upper respiratory system were also significantly increased among the welders. A dose-response relationship was found between exposure to welding fumes and the prevalence of symptoms from both the upper and lower respiratory system.

Adult↗