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Biomedical subjects

M Feher

Publications and source records attributed to M Feher.

14 recordsLinked to original sources
PubMed2001

Flexible alignment of small molecules.

A method is presented for flexibly aligning small molecules. The method accepts a collection of small molecules with 3D coordinates as input and computes a collection of alignments. Each alignment is given a score, which quantifies the quality of the alignment both in terms of internal strain and overlap of molecular features. The results of several computational experiments on pairs of compounds with known binding conformations are used to systematically and objectively tune the parameters for the method. The results indicate the method's utility for the elucidation of pharmacophores and comparative field analysis.

Databases, Factual↗
PubMed2001

Nonantioxidant functions of alpha-tocopherol in smooth muscle cells.

Most tocopherols and tocotrienols, with the exception of alpha-tocopherol, are not retained by humans. This suggests that alpha-tocopherol is recognized uniquely; therefore, it may exert an exclusive function. alpha-Tocopherol possesses distinct properties that are independent of its prooxidant, antioxidant or radical-scavenging ability. alpha-Tocopherol specifically inhibits protein kinase C, the growth of certain cells and the transcription of the CD36 and collagenase genes. Activation events have also been seen on the protein phosphatase 2A (PP(2)A) and on the expression of other genes (alpha-tropomyosin and connective tissue growth factor). Neither ss-tocopherol nor probucol possessed the same specialty functions as alpha-tocopherol. Recently, we isolated a new ubiquitous cytosolic alpha-tocopherol binding protein (TAP). Its motifs suggest that it is a member of the hydrophobic ligand-binding protein family (CRAL-TRIO). TAP may also be involved in the regulation of cellular alpha-tocopherol concentration and alpha-tocopherol-mediated signaling.

Cells, Cultured↗
PubMed2000

A simple model for the prediction of blood-brain partitioning.

We derived a simple model for the prediction of blood-brain barrier penetration using three descriptors. The model contains the calculated octanol-water partition coefficient, the number of hydrogen-bond acceptors in an aqueous medium and the polar surface area. It was validated using an extensive dataset, comprising 100 diverse drug molecules. The descriptors are easily calculated and the model is suitable for the rapid prediction of the blood-brain barrier partitioning of drugs.

Blood-Brain Barrier↗
PubMed2000

Specific cellular responses to alpha-tocopherol.

In the last 10 years precise cellular functions of alpha-tocopherol, some of which are independent of its antioxidant/radical-scavenging ability, have been revealed. Absorption of alpha-tocopherol from the gut is a selective process. Other tocopherols are not absorbed or are absorbed to a lesser extent. At the post-translational level, alpha-tocopherol inhibits protein kinase C and 5-lipoxygenase and activates protein phosphatase 2A and diacylglycerol kinase. Some genes [platelet glycoprotein IV/thrombospondin receptor/class B scavenger receptor (CD36), alpha-tocopherol transfer protein (alpha-TTP), alpha-tropomyosin, connective tissue growth factor and collagenase] are affected by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also inhibits cell proliferation, platelet aggregation, monocyte adhesion and the oxygen burst in neutrophils. Other antioxidants, such as beta-tocopherol and probucol, do not mimic these effects, suggesting a nonantioxidant, alpha-tocopherol-specific molecular mechanism.

Animals↗
PubMed2000

Current awareness

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Prediction; 7 Prevention; 8 Intervention: a&rpar General; b&rpar Pharmacology; 9 Pathology: a&rpar General; b&rpar Cardiovascular; c&rpar Neurological; d&rpar Renal; 10 Endocrinology & Metabolism; 11 Nutrition; 12 Animal Studies; 13 Techniques. Within each section, articles are listed in alphabetical order with respect to author (8 Weeks journals - Search completed at 19th Apr. 2000)

Journal Article↗
PubMed1996

Angiotensin-converting enzyme (ACE) gene polymorphism and the erythrocyte sodium-lithium countertransporter (SLC) phenotype in hypertension.

It has been suggested that the association between altered behaviour of the erythrocyte sodium-lithium countertransporter (SLC) and hypertension could be secondary to its association with the risk of vascular disease rather than raised blood pressure (BP) per se. Homozygosity for the angiotensin-converting enzyme (ACE) deletion allele has also been linked to a more severe phenotype for cardiovascular disease. The present study investigated whether there is an association between these two indicators of vascular risk in patients with hypertension. The kinetic characteristics of the countertransporter (SLC activity, Vmax and KNa) of patients having the ID ACE-genotype (n = 16) were compared with those patients who had the DD genotype (n = 12). The median (range) SLC activity (mmol Li/l Red Blood Cells.h) in the ID (0.221 [0.061-0.422]) and DD (0.173 [0.094-0.408]) groups were similar (P = 0.28; Mann-Whitney). No significant differences in Vmax (mmol Li/l RBC.h) emerged between the two study groups (0.279 + 0.124 [ID] vs 0.244 + 0.123 [DD]; P = 0.46; unpaired Student's t-test); similarly, no differences emerged between the two groups with respect to KNa (median [range]; ID, 39.8 [12.4-84.4] vs DD, 35.9 [14.6-78.3]; P = 0.47). These data suggest that the SLC phenotype and the ACE-D allele dose are risk factors for cardiovascular disease that function independently of one another.

Aged↗
PubMed1996

Blood pressure measurement in the community: do guidelines help?

The measurement of blood pressure (BP) is a crucial part of clinical assessment and hypertension management, and is commonly performed inaccurately despite the publication of National and International consensus guidelines for its measurement. There have been no previous reports on the self-reported knowledge-base of General Practitioners (GPs) and Practice Nurses (PNs) with regard to BP measurement. A postal questionnaire survey was conducted of 831 community-based practitioners (550 GPs and 281 PNs) in north west London. The overall response rate was 61%. Previous education in BP measurement was recorded in 87% of the GPs and 95% of the nurses. Precision factors were recorded for the GPs and nurses respectively including rounding up or down (GP 67%, PNs 48%), routine use of diastolic phase V (GP 63%, PNs 70%), reading the BP to the nearest 2 mm mercury (GP 54%, PNs 70%) and failure to use a large BP cuff in the past 4 weeks (GP 33%, PNs 26%). Only 12% of the GPs and 19% of the nurses were able to name the source of the published guidelines. Overall the nurses had a statistically significantly greater knowledge base than the GPs, and both community groups had a greater knowledge for core questions than hospital practitioners from two previous surveys. Knowledge of a guideline source was associated with improved self-reported BP technique. There was a difference between reading and recording accuracy which deserves further study. These results show that there are important gaps in the knowledge of community practitioners with regard to the technique of BP measurement.

Blood Pressure Determination↗
PubMed1992

Blood pressure measurement by junior hospital doctors--a gap in medical education?

A questionnaire survey, combined with an observational study, evaluated the knowledge of doctors in training grades on the practical aspects of blood pressure measurement. Eighty (non-consultant) junior hospital doctors, graduates from 30 separate medical schools, participated in the study. The results show that 27 (33%) doctors acknowledged no formal education on how to measure blood pressure. This lack of precise theoretical knowledge was matched by an observed poor clinical technique in over one third of the study group. The precision and accuracy of blood pressure recording is fundamental to the clinical examination of patients, and crucial in their management in both hospital and community settings. The findings of this study support the urgent need for further training and assessment of blood pressure measurement at undergraduate, and postgraduate level.

Blood Pressure Determination↗
PubMed1990

Antihypertensive drugs and the hypertensive diabetic patient.

Hypertension occurs in about 40% of patients with non-insulin-dependent diabetes mellitus (NIDDM) in whom the incidence of coronary heart disease is greatly increased. Disturbances in lipid metabolism may be an important contributory factor. Patterns of lipid change in uncomplicated NIDDM are characterised by a raised serum triglyceride and a reduced high density lipoprotein. It is therefore likely that therapy for hypertension associated with NIDDM may further influence an existing atherogenic lipid profile. Recent studies in diabetic subjects have shown that alpha-blockers are associated with a trend towards improving, while beta-blockers adversely affect, the lipid profile. Calcium antagonists and ACE inhibitors have no adverse effects on the lipid profile.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Fears and phobias in people with diabetes.

Phobic disorders are more common in people with diabetes than in the general population. The management of phobic disorders in patients with diabetes, particularly when associated with a fear of hypoglycaemia, is especially challenging and requires close collaboration between psychological medicine and diabetes teams. Difficulty in distinguishing symptoms of anxiety from those of hypoglycaemia, and the real dangers associated with hypoglycaemia, complicate the delivery of psychological interventions that are used routinely in the treatment of phobias. Avoidance of hypoglycaemia can lead to deterioration in diabetes control. This case report describes a man with Type 1 diabetes who developed agoraphobia with panic disorder, associated with fear of hypoglycaemia and deterioration in glycaemic control. The management of patients with diabetes and phobic disorders, with particular reference to those associated with fear of hypoglycaemia, is discussed.

Adult↗
PubMedDate not supplied

Metric and multidimensional scaling: efficient tools for clustering molecular conformations.

The application of metric and multidimensional scaling to conformer ensembles was demonstrated in this work. An automated process was devised to cluster and assign group memberships and cluster representatives. The method allows rapid clustering, leading to intuitive results that can be visually inspected. Multidimensional scaling was found to be superior to metric scaling for clustering conformers. The performance of different hierarchical clustering algorithms was compared using multidimensional plots, and the group average method was found to perform best.

Amino Acid Sequence↗
PubMedDate not supplied

Multiple flexible alignment with SEAL: a study of molecules acting on the colchicine binding site.

An extension of the steric and electrostatic alignment alignment (SEAL) method (MultiSEAL) is described that allows the overlay of multiple molecules and conformations. The method is well-suited for the systematic study of possible alignments, also revealing information about the conformational energies associated with a given overlay. It has been tested on three examples: angiotensin II antagonists, 5-HT3 antagonists, and dopaminergic compounds. The utility of the method is further demonstrated in an analysis of molecules that putatively bind to the colchicine site of tubulin. On the basis of its overlay with colchicine, allocolchicine, 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone, and combretastatin A-4, it appears that 2-methoxyestradiol (2-ME) is unlikely to fit the colchine site properly. The weak antimitotic activity of 2-ME may be explained by its partial fit in the site.

2-Methoxyestradiol↗