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Biomedical subjects

J A Howard

Publications and source records attributed to J A Howard.

At least 55 records · Page 3Linked to original sources
PubMed2000

4-Ethynyl-4-hydroxycyclohexan-1-one and 4-ethynyl-4-hydroxy-2,3,5, 6-tetramethylcyclohexa-2,5-dien-1-one.

The title compounds, C(8)H(10)O(2), (I), and C(12)H(14)O(2), (II), occurred as by-products in the controlled synthesis of a series of bis(gem-alkynols), prepared as part of an extensive study of synthon formation in simple gem-alkynol derivatives. The two 4-(gem-alkynol)-1-ones crystallize in space group P2(1)/c, (I) with Z' = 1 and (II) with Z' = 2. Both structures are dominated by O-H. O=C hydrogen bonds, which form simple chains in the cyclohexane derivative, (I), and centrosymmetric dimers, of both symmetry-independent molecules, in the cyclohexa-2,5-diene, (II). These strong synthons are further stabilized by C[triple-bond]C-H. O=C, C(methylene)-H.O(H) and C(methyl)-H.O(H) interactions. The direct intermolecular interactions between donors and acceptors in the gem-alkynol group, which characterize the bis(gem-alkynol) analogues of (I) and (II), are not present in the ketone derivatives studied here.

Journal Article↗
PubMed1999

Molecular farming of industrial proteins from transgenic maize.

Recombinant egg white avidin and bacterial B-glucuronidase (GUS) from transgenic maize have been commercially produced. High levels of expression were obtained in seed by employing the ubiquitin promoter from maize. The recombinant proteins had activities that were indistinguishable from their native counterparts. We have illustrated that down-stream activities in the production of these recombinant proteins, such as stabilizing the germplasm and processing for purification, were accomplished without any major obstacles. Avidin (A8706) and GUS (G2035) are currently marketed by Sigma Chemical Co.

Amino Acid Sequence↗
PubMed1998

Processing of transgenic corn seed and its effect on the recovery of recombinant beta-glucuronidase.

The tools of plant biotechnology that have been developed to improve agronomic traits are now being applied to generate recombinant protein products for the food, feed, and pharmaceutical industry. This study addresses several processing and protein recovery issues that are relevant to utilizing transgenic corn as a protein production system. The gus gene coding for beta-glucuronidase (rGUS) was stably integrated and expressed over four generations. The accumulation level of rGUS reached 0.4% of total extractable protein. Within the kernel, rGUS was preferentially accumulated in the germ even though a constitutive ubiquitin promoter was used to direct gus expression. Fourth-generation transgenic seed was used to investigate the effect of seed processing on the activity and the recovery of rGUS. Transgenic seed containing rGUS could be stored at an ambient temperature for up to two weeks and for at least three months at 10 degrees C without a significant loss of enzyme activity. rGUS exposed to dry heat was more stable in ground than in whole kernels. The enzyme stability was correlated with the moisture loss of the samples during the heating. Transgenic seed was dry-milled, fractionated, and hexane extracted to produce full-fat and defatted germ fractions. The results of the aqueous extraction of rGUS from ground kernels, full-fat germ, and defatted-germ samples revealed that approximately 10 times more rGUS per gram of solids could be extracted from the ground full-fat germ and defatted-germ than from the kernel samples. The extraction of corn oil from ground germ with hot hexane (60 degrees C) did not affect the extractable rGUS activity. rGUS was purified from ground kernels and full-fat germ extracts by ion exchange, hydrophobic interaction, and size exclusion chromatography. Similar purity and yield of rGUS were obtained from both extracts. Biochemical properties of rGUS purified from transgenic corn seed were similar to those of E. coli GUS.

Animal Feed↗
PubMed1997

Absolute configuration of (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), a metabotropic glutamate receptor antagonist.

The title compound, (+)-MCPG [(+)-alpha-(4-carboxyphenyl)-alpha-methylglycine, C10H11NO4], is an antagonist at certain subtypes of metabotropic glutamate (mGlu) receptors. (+)-MCPG has gained widespread acceptance as a tool for probing the physiological role of mGlu receptors in the central nervous system. As a result, mGlu receptors are now known to be involved in processes connected with learning and memory, modulation of synaptic transmission and the transmission of pain responses. (+)-MCPG crystallized in its zwitterionic form. Its absolute configuration was assigned as S from X-ray diffraction data collected at 150 K. The refined Flack parameter is consistent with this assignment, although the large e.s.d. associated with it introduces some ambiguity.

Benzoates↗
PubMed1996

Diastereoselective synthesis of all four isomers of 3-(4-chlorophenyl) glutamic acid: identification of the isomers responsible for the potentiation of L-homocysteic acid-evoked depolarizations in neonatal rat motoneurons.

All four isomers of 3-(4-chlorophenyl)glutamic acid (5-8) were prepared by diastereoselective synthesis. Addition of (6S)-(+)-bis-lactim ether 15 to cis-4-chlorocinnamate 12 gave a mixture comprising mainly the (2R,3S)- and (2R,3R)-isomers 5 and 6, respectively (in a ratio of 56:40), while addition of (6R)-(-)-bis-lactim ether 16 to 4-chlorocinnamate 12 gave a mixture comprising mainly the (2S,3R)- and (2S,3S)-isomers 8 and 7, respectively (in a ratio of 56:42). The four stereoisomers (5-8) were therefore conveniently prepared by addition of either 3-lithio-(6S)- or -(6R)-bis-lactim ether (15 or 16, respectively) to 4-chlorocinnamate 12 and separation of the resultant mixtures of diastereoisomers (23-26) by flash silica gel chromatography. The absolute configurations of 6 and 7 were confirmed by X-ray crystallography. Both the (2S,3S)- and (2S,3R)-isomers (7 and 8, respectively) at a concentration of 100 microM significantly potentiated depolarizations induced by 10 microM L-homocysteic acid (L-HCA) (% control +/- sem: 130.4 +/- 3.6, n = 20 and 114.5 +/- 2.4, n = 11, respectively) while the (2R,3S)-isomer 5 significantly reduced L-HCA response amplitude (94.2 +/- 1.4, n = 9) and the (2R,3R)-isomer 6 was inactive. Experiments designed to compare the agonist-potentiating actions of 7 and 8 in the neonatal rat spinal cord with L-trans-pyrrolidine-2,4-dicarboxylic acid, the well-known L-Glu uptake inhibitor, provided additional evidence for the selective enhancement of depolarizations due to L-HCA and not those due to L-Glu. This selective action supports the existence of multiple excitatory amino acid uptake sites.

Animals↗
PubMed1994

The impact of previous sexual abuse on children's adjustment in adoptive placement.

This article explores the effects of previous sexual abuse on the adjustment of children in adoptive placement. A conceptual model is used to interpret the findings of a study comparing the adoptive placements of 35 sexually abused children with the placements of 113 children who had no identified history of sexual abuse. Data were gathered from the children's case records. Results indicate that sexually abused children experienced more moves when in care, increased frequency of disrupted adoptive placements, greater behavioral difficulties, and more attachment problems than the comparison group. This article examines the interaction of sexual abuse and adoption issues and discusses the implications of the findings for social work practice with sexually abused children and their adoptive families.

Adoption↗
PubMed1992

The contribution of charge to affinity at functional (M3) muscarinic receptors in guinea-pig ileum assessed from the effects of the carbon analogue of 4-DAMP methiodide.

1. 4-Diphenylacetoxy-1:1-dimethyl cyclohexane (carbo-4-DAMP) is the carbon analogue of 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methiodide. The compounds differ only in that the quaternary nitrogen atom in 4-DAMP methiodide is replaced by a quaternary carbon atom, which is uncharged. 2. Carbo-4-DAMP appears to act competitively at functional (M3) muscarinic receptors in guinea-pig ileum. Estimates of log affinity constant are 6.0 at 30 degrees C and 5.9 at 37 degrees C, i.e. the compound has 0.1% of the affinity of 4-DAMP methobromide. 3. The absence of charge makes little difference to the conformation as determined by X-ray crystallography. The bond lengths and angles are very similar, though the bonds in the cyclohexane ring of carbo-4-DAMP are consistently slightly longer than those in the piperidinium ring of 4-DAMP methiodide, and the presence of the charge slightly reduces the space between molecules. 4. The difference between the affinities of 4-DAMP methobromide and carbo-4-DAMP indicates that the contribution of coulombic forces to the binding between 4-DAMP methiodide and muscarinic (M3) receptors is at least 17 kJ mol-1 (4.1 kcal mol-1) at 37 degrees C. How much this is an underestimate depends upon how much hydrophobic binding is greater with the uncharged compound.

Animals↗
PubMed1989

A comparison of the crystal structures of some quaternary trimethylammonium salts related to dopamine and noradrenaline with those of the corresponding amines: a comment on their nicotine-like biological activities.

The crystal structures of seven substituted phenethylammonium salts and one (phenylpropyl)-ammonium salt have been determined. (I) Trimethyl(phenethyl)ammonium iodide, C11H18N+.I-, Mr = 291.2, orthorhombic, P2(1)2(1)2(1) (No. 19), a = 6.040 (2), b = 7.689 (2), c = 26.528 (9) A, V = 1232 (1) A3, Z = 4, Dx = 1.56 g cm-3, Mo K alpha radiation (lambda = 0.71073 A), mu = 25.33 cm-1, F(000) = 576, T = 298 K, R (wR) = 0.0302 (0.0305) for 1991 reflections with I greater than 3 sigma (I). (II) (p-Hydroxyphenethyl)trimethylammonium iodide, C11H18NO+.I-, Mr = 307.2, triclinic, P1 (No. 2), a = 9.619 (1), b = 9.926 (1), c = 14.179 (2) A, alpha = 95.24 (1), beta = 97.50 (1), gamma = 98.97 (1) degrees, V = 1317.2 (3) A3, Z = 4, Dx = 1.55 g cm-3, Mo K alpha radiation (lambda = 0.71073 A), mu = 23.79 cm-1, F(000) = 608, T = 298 K, R (wR) = 0.0351 (0.0373) for 4320 reflections with I greater than 3 sigma (I). (III) (m-Hydroxyphenethyl)trimethylammonium iodide hemihydrate, C11H18NO+.I-.1/2H2O, Mr = 316.2, monoclinic, P2(1)/n (non-standard, No. 14), a = 8.048 (2), b = 9.782 (3), c = 17.447 (7) A, beta = 90.15 (1) degrees, V = 1374 (2) A3, Z = 4, Dx = 1.53 g cm-3, Mo K alpha radiation (lambda = 0.71073 A), mu = 22.86 cm-1, F(000) = 628, T = 298 K, R (wR) = 0.0719 (0.0655) for 1006 reflections with I greater than 1 sigma (I).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Temporomandibular disorders. Variation in clinical practice.

This research describes the extent of variability in diagnosis and treatment of temporomandibular disorders (TMD) and relates this variability to treatment outcomes. A health maintenance organization sequentially referred 145 patients with orofacial pain and dysfunction to two TMD clinics. The two clinics differed substantially in their use of tomography (applied to 28% vs. 64% of all patients), and varied moderately in diagnoses assigned to the patient groups. There was large variation in selection of treatments including appliances for bruxism (64% vs. 5%), mandibular repositioning (10% vs. 25%), and joint stabilization (3% vs. 30%); anti-inflammatory medications (44% vs. 19%) and analgesics (16% vs. 2%); and subsequent referral for dental or orthodontic treatment (1% vs. 42%). The differences in diagnostic and therapeutic practice that were found were not associated with important differences in patient-reported pain and dysfunction at 1-year follow-up. These data indicate the need for systematic approaches to identifying, evaluating, and modifying variation in health care practices for common presenting problems lacking reliable methods of evaluation and generally accepted clinical standards for choice of treatments.

Adult↗
PubMed1981

Self-concept of young children with cerebral palsy.

Several measures of self-concept and self-esteem were applied to a sample of 15 'mainstreamed', upper-middle-class, cerebral-palsied children aged between four and eight years, and to 15 matched controls. Over-all self-concept scores were similar for both groups, although they tended to be lower for the handicapped group. Teachers rated the handicapped children as having lower self-esteem than the controls in the classroom, but behavioral ratings by parents of their own children at home revealed no group differences in self-esteem. These tentative findings, supplemented by interview data, support the hypothesis that children with cerebral palsy begin to regard themselves as different as early as four years of age. However, these self-views and their potentially negative effects on self-esteem do not appear to crystallize until the children are in the primary grades at school.

Cerebral Palsy↗
PubMed1979

Developmental progression in play behavior of children between nine and thirty months. I: Spontaneous play and imitation.

The developmental progression of play behavior was studied cross-sectionally in 85 children at eight age-levels between nine and 30 months. In a structured play situation, three major play patterns were distinguished: (1) exploratory play (at the end of the first year); (2) functional play (beginning of second year); and (3) representational play (after 15 months). Sequential play first occurred at 21 months. Play behavior with spatial characteristics was also observed: relational and container play between nine and 15 months, and understanding of spatial relationships, stacking and grouping between 18 and 24 months. There was a significant relationship between spontaneous and imitative play behavior; the greatest affect was displayed when the demonstrated behaviors matched the child's developmental level of play.

Age Factors↗
PubMed1979

Developmental progression in play behavior of children between nine and thirty months: II: Spontaneous play and language development.

The relationship between play behavior displayed in a structured play situation and language development was studied cross-sectionally in 85 children at eight age--evels between nine and 30 months. There were no correlations between types of play behavior, in particular functional play (appropriate use of objects on the child's own body), representational play (appropriate use of objects on a doll or another person), or symbolic play (substitution of present objects for absent ones) and speech measures such as total number of words and of vocalizations, number of different words and different vocalizations, and number of sentences. Identification of objects upon verbal request was not related to any type of play behavior, but comprehension of verbal requests for functional or representational play was postively correlated with the display of functional or representational play. The children did not respond to verbal requests for functional or representational play unless these types of play behavior were part of their spontaneous play repertoire. Understanding of prepositions seemed to be related to spatial concepts expressed in play behavior, such as container play or arranging chairs around a table and setting the table.

Child Development↗
PubMed1979

Amniocentesis follow-up: infant developmental evaluation.

The Gesell Developmental Evaluation was administered to 150 children between 8 and 37 months of age whose mothers had second-trimester amniocentesis. The results of the evaluation were analyzed with respect to 1) maternal age at the time of the amniocentesis; 2) volume of fluid aspirated; 3) presence of bloody amniotic fluid; 4) repeat amniotic taps; and 5) medical problems during the first year of life. There was no statistical relationship found between an abnormal developmental score and any of the above 5 items. The results from the same developmental test administered to the control group of 64 young children were not significantly different from the index group.

Adult↗