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Biomedical subjects

M E Snow

Publications and source records attributed to M E Snow.

14 recordsLinked to original sources

Plasma androgens in autism.

Plasma levels of testosterone and the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S) were measured in male autistic subjects (31 prepubertal, 8 postpubertal), mentally retarded/cognitively impaired subjects (MR, 12 prepubertal), and normal control subjects (NC, 10 prepubertal, 11 postpubertal). Mean levels of plasma testosterone were similar in the postpubertal autistic (4.54 +/- 1.12 ng/ml) and postpubertal NC (5.02 +/- 1.87 ng/ml) groups. Plasma DHEA-S levels in postpubertal autistic (2170 +/- 1020 ng/ml) and postpubertal NC (1850 +/- 777 ng/ml) groups also were not significantly different. Similarly, no significant group differences were seen for testosterone or DHEA-S in the prepubertal autistic, MR, or NC individuals, although prepubertal MR individuals with cerebral palsy did have increased plasma DHEA-S levels compared to age-matched MR or NC individuals. Significant negative correlations were found between testosterone and whole blood serotonin (5-HT) levels in the combined (all subjects, all ages) groups and in the autistic group, suggesting that the effect of puberty on whole blood 5-HT may deserve further study. Data indicate that altered secretion of the androgens is not a common feature of autism. However, abnormalities of adrenal androgen secretion may be present in individuals with cerebral palsy.

Adolescent

A new method for building protein conformations from sequence alignments with homologues of known structure.

We describe a largely automatic procedure for building protein structures from sequence alignments with homologues of known structure. This procedure uses simple rules by which multiple sequence alignments can be translated into distance and chirality constraints, which are then used as input for distance geometry calculations. By this means one obtains an ensemble of conformations for the unknown structure that are compatible with the rules employed, and the differences among these conformations provide an indication of the reliability of the structure prediction. The overall approach is demonstrated here by applying it to several Kazal-type trypsin inhibitors, for which experimentally determined structures are available. On the basis of our experience with these test problems, we have further predicted the conformation of the human pancreatic secretory trypsin inhibitor, for which no experimentally determined structure is presently available.

Algorithms

Dimensional oscillation. A fast variation of energy embedding gives good results with the AMBER potential energy function.

The structure of the AMBER potential energy surface of the cyclic tetrapeptide cyclotetrasarcosyl is analyzed as a function of the dimensionality of coordinate space. It is found that the number of local energy minima decreases as the dimensionality of the space increases until some limit at which point equipotential subspaces appear. The applicability of energy embedding methods to finding global energy minima in this type of energy-conformation space is explored. Dimensional oscillation, a computationally fast variant of energy embedding is introduced and found to sample conformation space widely and to do a good job of finding global and near-global energy minima.

Computer Simulation

DSM-III and DSM-III-R diagnosis of autism and pervasive developmental disorder in nursery school children.

DSM-III and DSM-III-R diagnoses of 112 developmentally disordered preschool children were compared. There was no significant difference between the DSM-III and DSM-III-R diagnosis of the inclusive category of pervasive developmental disorder, but nearly twice as many cases (58) were diagnosed as autistic disorder by DSM-III-R criteria as were diagnosed as infantile autism (31) by DSM-III. Thirty children met both DSM-III and DSM-III-R criteria for autism (IA/AD) and 23 received a DSM-III diagnosis of atypical PDD (A-PDD) and a DSM-III-R diagnosis of AD (A-PDD/AD). All of the IA/AD children and none of the A-PDD/AD group displayed a marked lack of awareness of others. DSM-III-R criteria have specifically broadened the concept of autism to include children who, although socially impaired, are not pervasively unresponsive to others.

Autistic Disorder

Affect and cognition in autism.

An array of six photographs of the same woman was used to assess the ability of 18 autistic, 14 nonautistic mentally retarded, and 18 normal preschool subjects to use affect- and activity-related concepts in the solution of cognitive tasks. The Total Performance Level of the autistic and mentally retarded subjects did not differ significantly. Autistic subjects performed imitation, directed action, and description tasks less well in the affect mode. The findings are consistent with other studies, suggesting an impairment in the expression of emotion in autism.

Adolescent

A molecular-mechanics study of the conformation of the interchain disulfide of human immunoglobulin G4 (IgG4).

The conformation of the interchain disulfide bond between the light and the heavy chains of human immunoglobulin G4 (IgG4) was modeled based on the known structure of a human IgG1 Fab. Exploration of a large number of conformations followed by energy minimization using molecular mechanics methods rendered a plausible model for the disulfide. In this model the disulfide adopts the long, trans-gauche-trans configuration found in immunoglobulin intrachain bridges and not the conformations most commonly observed in other proteins (left-handed spiral or right-handed hook). Heavy chain residues H217 and H218 pack tightly against the disulfide and put restrictions on which sequences can exist in the proposed conformation. Sequence analysis at these positions shows that: (a) all human IgG4 and IgG3 are compatible with the model; (b) IgG2 and human immunoglobulins of other classes cannot adopt the conformation proposed for IgG4.

Disulfides

The postcardiotomy syndrome following transvenous pacemaker insertion.

We describe a syndrome of fever, pericarditis, and symptomatic pericardial effusion beginning 2 months after transvenous insertion of a permanent pacemaker in a 75-year-old woman. The syndrome improved dramatically following pericardiocentesis and resolved after subsequent administration of indomethacin. Although right ventricular perforation during pacemaker insertion was not recognized, inadvertent perforation leading to the postcardiotomy syndrome is postulated.

Aged

Calculating three-dimensional changes in protein structure due to amino-acid substitutions: the variable region of immunoglobulins.

A procedure (coupled perturbation procedure, CPP) is introduced as a specific method for calculating the detailed three-dimensional structure of a protein molecule which has a number of amino-acid substitutions relative to some previously determined "parent" protein structure. The accuracy of the procedure is tested by calculating the conformation of a region of the human immunoglobulin fragment Fab Kol based on the analogous region of the human immunoglobulin fragment Fab New. Both structures have previously been determined crystallographically. The calculated model is accurate to the extent that both of the sequence differences in the region are modeled correctly and that conformational changes in a number of nearby residues are correctly identified. CPP is shown to give better results than other commonly used modeling procedures when applied to the same problem.

Amino Acid Sequence

Regression of severe alcoholic cardiomyopathy after abstinence of 10 weeks.

Alcoholic cardiomyopathy usually has a poor prognosis, but the case presented here documents a dramatic regression of left ventricular dysfunction in a patient with alcoholic cardiomyopathy. Ejection fraction determined by echocardiography increased from 12% at the time of presentation to 45% 10 weeks later. This was associated with clinical resolution of congestive heart failure and a decrease in cardiac and left ventricular size documented by chest x-ray and echocardiography.

Cardiac Catheterization

A 1.8 A resolution potential function for protein folding.

A general method is presented for constructing a potential function for approximate conformational calculations on globular proteins. The method involves solving a nonlinear program that seeks to adjust the potential's parameters in such a way that a minimum near the native remains a minimum and does not move far away, while any alternative minima shift so as to remain local minima but eventually rise higher than the level of the near-native minimum. Although the potential trades computational speed for detail by representing each amino acid residue as only a single point, correct secondary structural preferences and reasonable tertiary folding can be built into the potential in an entirely routine way. The potential has been parameterized to agree with the crystal structure of avian pancreatic polypeptide (having 36 residues) in the sense that the lowest minimum found (-407 arbitrary units) is reasonably close to the native (1.8 A rms interresidue distance deviation). In contrast, the lowest nonnative conformation found after extensive searches by a variety of methods was -399 units and 7.5 A away. Such potentials may prove to be useful in predicting approximate tertiary structure from amino acid sequence, if they can be generalized to apply to more than one protein.

Methods