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Biomedical subjects

B A Lewis

Publications and source records attributed to B A Lewis.

At least 37 records · Page 2Linked to original sources

Segregation analysis of speech and language disorders.

Complex segregation analysis was performed on pedigrees ascertained through 45 probands (26 males, 19 females) with a history of preschool speech and language disorders. Hypotheses concerning mode of inheritance were tested using the POINTER segregation analysis program. Although there is strong evidence for familial transmission of this trait, we were unable to distinguish between a major gene and multifactorial transmission model using likelihood-ratio chi-square tests. Future studies with quantitative measures of speech and language disorders are needed to resolve the issue of mode of inheritance for this trait.

Adolescent↗

Residual effects of preschool phonology disorders in grade school, adolescence, and adulthood.

This study used a cross-sectional design to examine the performance of people with a history of a preschool phonology disorder on measures of phonology, reading, and spelling at preschool age (n = 20), grade school age (n = 23), adolescence (n = 17), and adulthood (n = 17). Results showed that at each age group, subjects with a history of a disorder performed more poorly than control subjects matched for age, sex, and socioeconomic status in all domains. Comparisons across each successive age group revealed a higher performance on measures from preschool to grade school age, and a smaller but steady improvement from grade school age to adolescence to adulthood. Subjects with a history of other language problems, in addition to the phonology disorder overall, performed more poorly than subjects with a history of a preschool phonology disorder alone on the reading and spelling measures. These findings suggest that remnants of a preschool phonology disorder are detectable past grade school age and into adulthood.

Adolescent↗

A study of developmental speech and language disorders in twins.

Fifty-seven same-sex twin sets (32 monozygotic and 25 dizygotic) were examined for concordance of speech and language disorders. Results showed monozygotic twins to have higher concordance than dizygotic twins. In addition, monozygotic twins were more similar in the types of disorders they presented than dizygotic twins. Positive family histories for speech, language, and learning disorders were reported in the nuclear families of the twins.

Child↗

Origins of the osmoprotective properties of betaine and proline in Escherichia coli K-12.

The amounts of cytoplasmic water and of all osmotically significant cytoplasmic solutes were determined for Escherichia coli K-12 grown in 3-(N-morpholino)propane sulfonate (MOPS)-buffered glucose-minimal medium containing 0.5 M NaCl in the presence and absence of the osmoprotectants betaine and proline. The goal of this work is to correlate the effects of osmoprotectants on the composition of the cytoplasm with their ability to increase the growth rate of osmotically stressed cells. At a concentration of 1 mM in the growth medium, betaine increases the growth rate more than does proline; choline, which is converted to betaine by E. coli, appears to have an intermediate effect on growth rate. The accumulation of either betaine or proline reduces the cytoplasmic amounts of K+, glutamate, trehalose, and MOPS (the major cytoplasmic osmolytes accumulated in the absence of osmoprotectants), so that at this external osmolarity the total amount of cytoplasmic solutes is essentially the same in the presence or absence of either osmoprotectant. More betaine than proline is accumulated, so the extent of replacement of cytoplasmic solutes is greater for betaine than for proline. Accumulation of these osmoprotectants is accompanied by a large (20 to 50%) increase in the volume of cytoplasmic water per unit of cell dry weight (Vcyto). This effect, which appears to result from an increase in the volume of free water, Vf (as opposed to water of hydration, or bound water), is greater for betaine than for proline. Taken together, these results indicate that the molar effects of betaine and proline on water activity and on the osmotic pressure of the cytoplasm must be significantly larger than those of the solutes they replace. Cayley et al. (S. Cayley, B. A. Lewis, H. J. Guttman, and M. T. Record, Jr., J. Mol. Biol. 222:281-300, 1991) observed that, in cells grown in the absence of osmoprotectants, both growth rate and Vcyto decreased, whereas the amount of cytoplasmic K+ (nK+) increased, with increasing external osmolarity. We predicted that the observed changes in nK+ and Vcyto would have large and approximately compensating effects on key protein-nucleic acid interactions of gene expression, and we proposed that Vf was the fundamental determinant of growth rate in osmotically stressed cells. The properties of cells cultured in the presence of betaine and proline appear completely consistent with our previous work and proposals. Accumulation of betaine and, to a lesser extent, proline shifts the set of linked physiological parameters (nK+, Vcyto, growth rate) to those characteristic of growth at lower osmolarity in the absence of osmoprotectants. Models for the thermodynamic basis and physiological consequences of the effect of osmoprotectants on Vcyto and Vf are discussed.

Betaine↗

Pedigree analysis of children with phonology disorders.

This study examined 87 pedigrees of individuals with histories of preschool phonology disorders. Results confirmed previous reports that speech and language disorders aggregate in families, with a higher incidence of males affected than females. Significantly more family members with dyslexia and learning disabilities, but not stuttering or hearing impairment, were found in pedigrees of individuals with phonology disorders than in pedigrees of nondisabled individuals. Probands with and without additional language problems did not differ in the incidence of affected family members. Nuclear family members demonstrated a higher incidence of disorders than when all family members were considered, with brothers of probands most often affected. Pedigrees of female probands had more affected members in their nuclear families than pedigrees of male probands.

Adolescent↗

Mechanical properties of dental base materials.

The compressive strengths and compressive moduli of seven base materials (Dycal, VLC Dycal, Time-line, Vitrabond, Ketac Bond, Fuji Lining LC, XR-Ionomer) were measured at 7 minutes, 24 hours, and 90 days using 9 mm by 4 mm cylindrical specimens prepared in hollow Teflon tubes. The 24-hour and 90-day specimens were maintained for 1 hour at 37 degrees C with relative humidity greater than 30%, then placed in distilled water at 37 degrees C until testing. After grinding the ends of the specimens flat, the cylinders of base material were loaded at 1.0 mm/min in an Instron. The compressive strengths of Timeline, a resin based material, at 7 minutes, 24 hours, and 90 days were not significantly different. Timeline had significantly greater compressive strengths of all time periods than the other six materials. The compressive strength of both Dycal and VLC Dycal decreased significantly between the 24-hour and 90-day periods. Of the three photosensitive GI base/liners tested, Fuji Lining LC had significantly higher compressive strengths in all three time periods. At 7 minutes, Timeline demonstrated a significantly higher compressive modulus than any other product. Ketac Bond had a significantly higher compressive modulus at 24 hours and 90 days.

Analysis of Variance↗

Characterization of the cytoplasm of Escherichia coli K-12 as a function of external osmolarity. Implications for protein-DNA interactions in vivo.

The water-accessible volumes, the amounts of all significant osmolytes, and the protein concentration in the cytoplasm of aerobically grown Escherichia coli K-12 have been determined as a function of the osmolarity of the minimal growth medium. The volume of cytoplasmic water (Vcyto) decreases linearly with increasing osmolarity from 2.23(+/- 0.12) microliters/mg dry weight in cells grown at 0.10 OSM to 1.18(+/- 0.06) microliters/mg dry weight at 1.02 OSM. Above 0.28 OSM, growth rate decreases linearly with increasing osmolarity. The growth rate extrapolates to zero at an osmolarity of approximately 1.8, corresponding to an estimated Vcyto of 0.5(+/- 0.2) microliters/mg dry weight. Measurements of Vcyto in titrations of non-growing cells with the plasmolyzing agent NaCl were used to obtain volumes of "bound" water (presumably water of macromolecular hydration) and cytoplasmic osmotic coefficients for cells grown in medium of low (0.10 OSM) and moderate (0.28 OSM) osmolarity. The volume of bound water Vb is similar in the two osmotic conditions (Vb = 0.40(+/- 0.04) microliters/mg dry wt), and corresponds to approximately 0.5 g H2O/g cytoplasmic macromolecule. Since Vcyto decreases with increasing osmolarity, whereas Vb appears to be independent of osmolarity, water of hydration becomes a larger fraction of Vcyto as the osmolarity of the growth medium increases. Growth appears to cease at the osmolarity where Vcyto is approximately equal to Vb. K+ and glutamate (Glu-) are the only significant cytoplasmic osmolytes in cells grown in medium of low osmolarity. The amount of K+ greatly exceeds that of Glu-. Analysis of cytoplasmic electroneutrality indicates that the cytoplasm behaves like a concentrated solution of the K+ salt of cytoplasmic polyanions, in which the amount of additional electrolyte (K+ Glu-) increases with increasing osmolarity. As the osmolarity of the growth medium becomes very low, the cytoplasm approaches an electrolyte-free K+-polyanion solution. In vivo osmotic coefficients were determined from the variation of Vcyto with external osmolarity in plasmolysis titrations of non-growing cells. The values obtained (phi = 0.54(+/- 0.06) for cells grown at 0.10 OSM and phi = 0.71(+/- 0.11) at 0.28 OSM) indicate a high degree of non-ideality of intracellular ions arising from coulombic interactions between K+ and cytoplasmic polyanions. Analysis of these osmotic coefficients using polyelectrolyte theory indicates that the thermodynamic activity of cytoplasmic K+ increases from approximately 0.14 M in cells grown at an external osmolarity of 0.10 OSM to approximately 0.76 M at 1.02 OSM.(ABSTRACT TRUNCATED AT 400 WORDS)

Biophysical Phenomena↗

Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition.

There is a need to standardize the NDF procedure. Procedures have varied because of the use of different amylases in attempts to remove starch interference. The original Bacillus subtilis enzyme Type IIIA (XIA) no longer is available and has been replaced by a less effective enzyme. For fiber work, a new enzyme has received AOAC approval and is rapidly displacing other amylases in analytical work. This enzyme is available from Sigma (Number A3306; Sigma Chemical Co., St. Louis, MO). The original publications for NDF and ADF (43, 53) and the Agricultural Handbook 379 (14) are obsolete and of historical interest only. Up to date procedures should be followed. Triethylene glycol has replaced 2-ethoxyethanol because of reported toxicity. Considerable development in regard to fiber methods has occurred over the past 5 yr because of a redefinition of dietary fiber for man and monogastric animals that includes lignin and all polysaccharides resistant to mammalian digestive enzymes. In addition to NDF, new improved methods for total dietary fiber and nonstarch polysaccharides including pectin and beta-glucans now are available. The latter are also of interest in rumen fermentation. Unlike starch, their fermentations are like that of cellulose but faster and yield no lactic acid. Physical and biological properties of carbohydrate fractions are more important than their intrinsic composition.

Animal Feed↗

Analysis of foodstuffs for dietary fiber by the urea enzymatic dialysis method.

Total dietary fiber (TDF) values for cereal grains, fruits, vegetables, processed foods, and purified or semi-purified dietary fiber products were determined by a new method using 8M urea and enzymes (urea enzymatic dialysis, UED, method). The results are compared with the official AOAC procedure. Soluble and insoluble dietary fiber were determined for several of these foodstuffs and compared with the NDF values. Crude protein and ash contamination was usually lower with the UED method compared with the AOAC method, particularly for samples that formed gels during ethanol precipitation. Urea and the heat stable amylase were effective in removing starch even at relatively low temperatures of the assay (50 degrees C). The new assay is relatively economical in use of equipment, enzymes, and reagents. Studies are currently in progress to minimize the assay time for the UED method while further improving its flexibility and robustness. The results of the studies will be discussed.

Amylases↗

Familial phonological disorders: four pedigrees.

The pedigrees of 4 children with a severe phonological disorder demonstrating three generations of members with speech/language problems are presented. All 4 probands were female with two mothers, two fathers, and five out of six siblings affected. All pedigrees contained family members with dyslexia and learning disabilities as well as speech disorders. Family members varied in the type of speech problems that they demonstrated and the severity of their disorder, thus suggesting variable expressivity and incomplete penetrance. An autosomal dominant mode, a multifactorial-polygenic model, and a sex-specific threshold model for expression are discussed.

Child↗

Increased retinoblastoma gene expression is associated with late stages of differentiation in many different cell types.

The retinoblastoma (Rb) gene is a recessive oncogene or tumor-suppressor gene whose inactivation leads to the development of tumors. Recently, evidence pointing to a role for the Rb gene in the differentiation of certain human cell types has been presented. We have studied three mouse cell lineages to determine whether there is a correlation between Rb gene expression and differentiation. We find that induction of mouse erythroleukemia cell differentiation with either dimethylsulfoxide (DMSO) or hexamethylene bisacetamide (HMBA) leads to increased expression of Rb mRNA. Increased expression of Rb mRNA was also found in S2 myoblasts induced by mitogen depletion to become differentiated myotubes. In the B-cell lineage, Rb expression is low in pre-B and B cell lines but high in plasmacytomas, which represent late stages of B cell differentiation. Thus, in all three lineages (erythroid, muscle, and B-cell) late stages of differentiation are associated with increased amounts of Rb mRNA.

Acetamides↗

A familial study of severe phonological disorders.

The present study examined the familial basis for severe phonological disorders. Twenty children with severe phonological disorders and their siblings were compared to 20 normally developing children and their siblings on measures of phonology, language, reading, and motor ability. Results revealed that the siblings of the disordered children performed more poorly than control siblings on phonology and reading measures. Disordered subjects' phonological skills correlated significantly and positively with their siblings', whereas controls' scores did not. Families of disordered children reported significantly more members with speech and language disorders and dyslexia than did families of controls. Sex differences were reflected in the incidence but not the severity or type of disorder present. These findings suggest a familial basis for at least some forms of severe phonological disorders.

Child↗

Accumulation of 3-(N-morpholino)propanesulfonate by osmotically stressed Escherichia coli K-12.

We found that exogenous morpholinopropanesulfonate (MOPS) is concentrated approximately fivefold in the free volume of the cytoplasm of Escherichia coli K-12 (strain MG1665) when grown at high osmolarity (1.1 OsM) in two different media containing 40 mM MOPS. MOPS was not accumulated by E. coli grown in low-osmolarity MOPS-buffered medium or in 1.1 OsM MOPS-buffered medium containing the osmoprotectant glycine betaine. Salmonella typhimurium LT2 did not accumulate MOPS under any condition examined. We infer that accumulation of MOPS by E. coli K-12 is not due to passive equilibration but rather to transport, possibly involving an as yet uncharacterized porter not present in S. typhimurium. Glutamate and MOPS were the only anionic osmolytes we observed by 13C nuclear magnetic resonance in E. coli K-12 grown in MOPS-buffered medium. The increase in positive charge accompanying the increase in the steady-state amount of K+ in cells shifted from low to high external osmolarity appeared to be compensated for by changes in the amounts of putrescine, glutamate, and MOPS. MOPS is not an osmoprotectant, because its accumulation did not increase cell growth rate.

Betaine↗

Language and motor findings in benign megalencephaly.

9 children between the ages of 5 and 12 yr. whose head circumferences were greater than the 98th percentile and showed negative CT scans and histories for disease associated with increased brain size were studied. A battery of language, articulation, intelligence, and motor tests were administered to subjects and in each case to a sibling whose head circumference was normal. Analysis showed few differences in intelligence and language comprehension between the megalencephalic children and their siblings. Significant differences were observed in motor proficiency, with over 50% of the megalencephalic children scoring below the 10th percentile for their age group. Three megalencephalic children displayed articulation errors. All subjects had at least one parent whose head circumference exceeded the 98th percentile. These results suggest a relationship between benign megalencephaly and developmental motor difficulties.

Cephalometry↗

Identification of ninhydrin-positive caprolactam metabolites in the rat.

Caprolactam (2-oxohexamethylenimine) is metabolized in the rat partly to 4-hydroxycaprolactam or the corresponding free acid. The 4-hydroxy metabolite rearranges spontaneously in acidic aqueous medium to an equilibrium mixture of which 6-amino-gamma-caprolactone is the major component and 6-amino-4-hydroxyhexanoic acid is a minor component. Approximately 16% of the caprolactam ingested daily by rats fed a diet containing 3% caprolactam was excreted as the 4-hydroxy metabolite and a small amount was excreted as the non-hydroxylated acid, 6-aminohexanoic acid. The metabolites were isolated by ion-exchange chromatography and identified by gas chromatography-mass spectroscopy and infra-red and nuclear magnetic resonance spectroscopy.

Amino Acids↗

Immunological characterization of an exopolysaccharide from the Staphylococcus aureus strain Smith diffuse.

Exopolysaccharides (EXPs) of Staphylococcus aureus are associated with virulence in animal models. An EXP from the S. aureus strain Smith diffuse was previously detected in 64.3% of S. aureus clinical isolates. EXP was isolated from culture supernatants of this strain after DNAase, RNAase, phosphodiesterase I and lysostaphin treatment, and was further purified by cation-exchange and molecular-sieve chromatography. Isoelectric focusing revealed a pI of 3.6 for the EXP while the pI of teichoic acid was less than 2.7. Crossed immunoelectrophoresis with homologous Smith diffuse antisera indicated that the EXP contained two immunological components. A major precipitin line persisted after the antisera had been absorbed with the non-EXP-producing variant strain, Smith compact, while the second component was removed. Tandem immunoelectrophoresis also demonstrated that the EXP was distinct from teichoic acid. The EXP contained 2-amino-2-deoxyglucuronic acid, glucose, mannose and galactose. No fatty acids or nucleic acids were present and total protein content was less than 2%. Teichoic acid could not be demonstrated in the EXP, thus further substantiating the immunological studies. S. aureus EXP isolated by the present method can be used for further serological and virulence studies.

Antigens, Bacterial↗

NMR structural analysis of a membrane protein: bacteriorhodopsin peptide backbone orientation and motion.

In reconstituted vesicles above the lipid phase transition temperature, bacteriorhodopsin (BR) undergoes rotational diffusion about an axis perpendicular to the plane of the bilayer [Cherry, R. J., Muller, U., & Schneider, G. (1977) FEBS Lett. 80, 465]. This diffusion narrows the 13C NMR powder line shape of the BR peptide carbonyls. In contrast, BR in native purple membrane is relatively immobile and exhibits a rigid-lattice powder line shape. By use of the principal values of the rigid-lattice chemical shift tensor and the motionally narrowed line shape from the reconstituted system, the range of Euler angles of the leucine peptide groups relative to the diffusion axis has been calculated. The experimentally observed line shape is inconsistent with those expected for structures which consist entirely of either alpha helix or beta sheet perpendicular to the membrane or beta sheet tilted at angles up to about 60 degrees from the membrane normal. However, for two more complex structural models, the predicted line shapes agree well with the experimental one. These are, first, a structure consisting entirely of alpha1 helices tilted at 20 degrees from the membrane normal and, second, a combination of 60% alpha II helix perpendicular to the membrane plane and 40% antiparallel beta sheet tilted at 10-20 degrees from the membrane normal. The results also indicate that the peptide backbone of bacteriorhodopsin in native purple membrane is extremely rigid even at 40 degrees. The experiments presented here demonstrate a new approach, using solid-state nuclear magnetic resonance (NMR) methods, for structural studies of transmembrane proteins in fluid membrane environments, either natural or reconstituted.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriorhodopsins↗

Genetic amniocentesis: a twelve years' experience.

The first 2,013 fetuses in 2,000 patients undergoing genetic amniocentesis at our institution were analyzed for the incidence of abnormal findings and for the safety and accuracy of the procedure. One percent of the patients were found to have aneuploid fetuses and another 1% were found to have elevated amniotic fluid concentrations of alpha-fetoprotein. Advanced maternal age was the indication for amniocentesis in 84% of the women with aneuploid fetuses. Thirty-two (1.6%) of the pregnancies ended in spontaneous abortion and 35 (1.7%) were terminated because of abnormal results of the prenatal diagnostic procedure. Our error rate was 0.15%, and tissue culture was successful in 97.7% of the procedures. During the latter part of our experience concurrent ultrasonography was utilized with the amniocentesis, resulting in a reduction in blood-tinged specimens from 15.0% to 5.2%. In experienced hands, midtrimester amniocentesis for the purpose of prenatal diagnosis of genetically determined defects is a safe, accurate, and valuable procedure for the identification of fetal abnormalities.

Adult↗