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Biomedical subjects

C Hughes

Publications and source records attributed to C Hughes.

At least 163 records · Page 9Linked to original sources

Validation and assessment of a conversational interaction intervention.

Multiple measures of social behavior were obtained in order to (a) evaluate the effects of a systematic replication of a conversational interaction intervention, (b) identify critical target behaviors, (c) select participants likely to benefit from intervention, and (d) assess the social and experimental validity of the intervention. Combined measures (e.g., performance screening, assessing students' goals, behavioral ratings) corroborated the decision to introduce multiple-exemplar, self-instructional training to 4 students with moderate mental retardation who were observed to have limited social interaction with their peers at school. Findings indicated that the procedure was effective at increasing empirical indicators of participants' generalized conversational interaction and that behavioral change was validated socially by ratings of peers and important others.

Humans↗

Selection of sputum specimens for microbiological examination.

The purpose of this study was to compare the leucocyte esterase (LE) strip test with direct microscopy of Gram-stained sputum smears for the demonstration of leucocytes (WBC) and to develop a simple method for selecting specimens suitable for cultural examination. A total of 11% of specimens were demonstrated to be unsuitable for bacteriological examination using the proposed algorithm. It is thought that this technique offers a simple alternative to traditional microscopy alone for screening sputum specimens.

Algorithms↗

Methods for displaying macromolecular structural uncertainty: application to the globins.

Most molecular graphics programs ignore any uncertainty in the atomic coordinates being displayed. Structures are displayed in terms of perfect points, spheres, and lines with no uncertainty. However, all experimental methods for defining structures, and many methods for predicting and comparing structures, associate uncertainties with each atomic coordinate. We have developed graphical representations that highlight these uncertainties. These representations are encapsulated in a new interactive display program, PROTEAND. PROTEAND represents structural uncertainty in three ways: (1) The traditional way: The program shows a collection of structures as superposed and overlapped stick-figure models. (2) Ellipsoids: At each atom position, the program shows an ellipsoid derived from a three-dimensional Gaussian model of uncertainty. This probabilistic model provides additional information about the relationship between atoms that can be displayed as a correlation matrix. (3) Rigid-body volumes: Using clouds of dots, the program can show the range of rigid-body motion of selected substructures, such as individual alpha helices. We illustrate the utility of these display modalities by the applying PROTEAND to the globin family of proteins, and show that certain types of structural variation are best illustrated with different methods of display.

Animals↗

Rocky Mountain "spotless" fever with an erythema migrans-like skin lesion.

We report a case of Rocky Mountain "spotless" fever with a localized rash at the site of the tick bite that resembled the erythema migrans rash of Lyme borreliosis. Physicians who practice in geographic areas where Rocky Mountain spotted fever occurs should be aware of this unusual presentation.

Aged↗

A cell-surface polysaccharide that facilitates rapid population migration by differentiated swarm cells of Proteus mirabilis.

Swarming by Proteus mirabilis is characterized by cycles of rapid population migration across surfaces, following differentiation of typical vegetative rods into long, hyperflagellated, virulent swarm cells. A swarm-defective TnphoA insertion mutant was isolated that was not defective in cell motility, differentiation or control of the migration cycle, but was specifically impaired in the ability to undergo surface translocation as a multicellular mass. The mutation, previously shown to compromise urinary tract virulence, was located within a 1112 bp gene that restored normal swarming of the mutant when expressed in trans. The gene encoded a 40.6 kDa protein that is related to putative sugar transferases required for lipopolysaccharide (LPS) core modification in Shigella and Salmonella. The immediately distal open reading frame encoded a protein that is related to dehydrogenases involved in the synthesis of LPS O-side-chains, enterobacterial common antigen and extracellular polysaccharide (PS). Gel electrophoresis and electron microscopy showed that the mutant still made LPS but it had lost the ability to assemble a surface (capsular) PS, which gas-liquid chromatography and mass spectrometry indicated to be an acidic type II molecule rich in galacturonic acid and galactosamine. We suggest that this surface PS facilitates translocation of differentiated cell populations by reducing surface friction.

Amino Acid Sequence↗

Requirement for FlhA in flagella assembly and swarm-cell differentiation by Proteus mirabilis.

Swarming by Proteus mirabilis is characterized by cycles of rapid population migration across surfaces, following differentiation of typical rods into long, aseptate swarm cells that overexpress flagella and virulence factors, particularly haemolysin. A non-swarming Tn5phoA mutant was unable to synthesize flagella, to fully elongate or to induce high levels of the toxin. The mutation lay within a 2091 bp gene encoding a homologue of the Escherichia coli FlhA belonging to a family of proteins that are required for assembly of flagella or virulence proteins and that are suggested to act either directly in membrane translocation and/or in regulating synthesis of the export apparatus. In trans expression of multicopy flhA restored cell elongation and migration and generated differentiation-specific hyperexpression of flagellin and toxin genes to levels above those seen in the wild-type strain. Transcription of flhA was strongly induced during differentiation, from its own putative sigma 28 promoter. The results suggest a mechanistic coupling of flagella assembly and swarm-cell differentiation.

Amino Acid Sequence↗

Protein exporter function and in vitro ATPase activity are correlated in ABC-domain mutants of HlyB.

The Escherichia coli toxin exporter HlyB comprises an integral membrane domain fused to a cytoplasmic domain of the ATP-binding cassette (ABC) super-family, and it directs translocation of the 110kDa haemolysin protein out of the bacterial cell without using an N-terminal secretion signal peptide. We have exploited the ability to purify the soluble HlyB ABC domain as a fusion with glutathione S-transferase to obtain a direct correlation of the in vivo export of protein by HlyB with the degree of ATP binding and hydrolysis measured in vitro. Mutations in residues that are invariant or highly conserved in the ATP-binding fold and glycine-rich linker peptide of prokaryotic and eukaryotic ABC transporters caused a complete loss of both HlyB exporter function and ATPase activity in proteins still able to bind ATP effectively and undergo ATP-induced conformational change. Mutation of less-conserved residues caused reduced export and ATP hydrolysis, but not ATP binding, whereas substitutions of poorly conserved residues did not impair activity either in vivo or in vitro. The data show that protein export by HlyB has an absolute requirement for the hydrolysis of ATP bound by its cytoplasmic domain and indicate that comparable mutations that disable other prokaryotic and eukaryotic ABC transporters also cause a specific loss of enzymatic activity.

ATP-Binding Cassette Transporters↗

Interaction of persons with severe mental retardation and their nondisabled co-workers in integrated work settings.

This investigation matched 23 workers with severe mental retardation to 23 workers without disabilities by job type and minimal duration of employment (at least 6 months) to determine if co-worker relations differed between the two groups of employees. Results indicated that, compared to workers with severe mental retardation, nondisabled workers were more likely to receive information, to receive training, and to interact as friends outside the workplace.

Adult↗

The effects of multiple-exemplar self-instructional training on high school students' generalized conversational interactions.

A multiple-baseline-across-students design was used to investigate the effects of multiple-exemplar self-instructional training on the acquisition and generalization of conversational interaction of 4 high school students with mental retardation. The multiple-exemplar component of the model consisted of (a) several peers without disabilities teaching the use of a self-instructional social skills strategy across diverse examples of conversational interactions and across two settings and (b) assessing the generalized effects of training across additional peers and one setting. Findings indicated that peers were effective in teaching the multiple-exemplar strategy and that peer training was associated with systematic increases in generalized conversational interactions with familiar and unfamiliar peers with and without disabilities in an additional setting. Social validation data indicated that following multiple-exemplar training, all participants' performances approximated those of general education students and was judged by others to have improved.

Journal Article↗

The effect of neonatal exposure to diethylstilbestrol, coumestrol, and beta-sitosterol on pituitary responsiveness and sexually dimorphic nucleus volume in the castrated adult rat.

The neonatal hormone environment influences the sexually differentiated patterns of development. Estrogens, derived from intracerebral aromatization, promote male pattern development of the central nervous system. The purpose of this study was to determine the effects of neonatal exposure to environmental estrogens on luteinizing hormone (LH) secretion and development of the sexually dimorphic nucleus of the medial preoptic area (SDN-POA) in castrated adult rats. Neonatal rats of both sexes received injections of either corn oil, 0.1 microgram diethylstilbestrol (DES), 3 micrograms beta-sitosterol (B1), 30 micrograms beta-sitosterol (B2), 0.1 microgram coumestrol (C1), 1 microgram coumestrol (C2), or 10 micrograms coumestrol (C3) on Day 1-10 of life and were castrated on Day 21. Right heart catheters were placed on Day 42, and GnRH (50 ng/kg) was administered. Blood was sampled for LH at 0-, 5-, 10-, 15-, and 30-min intervals. All doses of beta-sitosterol and coumestrol elicited increased basal levels of LH in females. In males, B1, B2, C2, and C3 increased basal levels of LH. The GnRH-induced LH increase was prevented in females treated with diethylstilbestrol and 10 micrograms of coumestrol. Males in all treatment groups exhibited GnRH-induced LH surges. The animals were sacrificed by decapitation on Day 49. Volumes of the SDN-POA of the groups were compared. Treatment with the agents did not result in significantly increased SDN volume in females; nor was there a difference in SDN size among the male groups. These data show that exposure to environmental estrogens early in development alters both postpubertal pituitary response to GnRH and basal LH secretion in females and alters only basal LH secretion in males. No significant enlargement (i.e., masculinization) of the SDN-POA was exhibited.

Animals↗

Quality of life in applied research: a review and analysis of empirical measures.

A consensus list of 15 dimensions and corresponding components of quality of life was derived from the literature and proposed as a conceptual model. Eighty-seven empirical studies found in the applied research then were analyzed, and the proposed model was found to be supported by 1,243 empirical measures. In addition, studies were analyzed with respect to (a) demographic variables, (b) type of investigation, (c) method of assessment, (d) psychometric properties of assessments used, and (e) common dimensions of measures investigated and their frequency of measurement. Based upon findings, issues regarding methodology, implications for policy and practice in the field, and recommendations for future research were discussed.

Humans↗

Protamine reaction in a patient undergoing coronary artery bypass grafting.

The neutralization of heparin anticoagulation is accomplished by the administration of protamine. While the administration of protamine is generally uneventful, allergic reactions can occur. This article describes such a reaction in a patient having cardiac surgery. Classification of protamine reactions and signs and symptoms are discussed. Treatment and management of high risk patients is highlighted.

Aged↗

Fatty acylation of two internal lysine residues required for the toxic activity of Escherichia coli hemolysin.

Hemolysin of Escherichia coli is activated by fatty acylation of the protoxin, directed by the putative acyl transferase HlyC and by acyl carrier protein (ACP). Mass spectrometry and Edman degradation of proteolytic products from mature toxin activated in vitro with tritium-labeled acylACP revealed two fatty-acylated internal lysine residues, lysine 564 and lysine 690. Resistance of the acylation to chemical treatments suggested that fatty acid was amide linked. Substitution of the two lysines confirmed that they were the only sites of acylation and showed that although each was acylated in the absence of the other, both sites were required for in vivo toxin activity.

Acyl Carrier Protein↗

Induction of T helper cell hyporesponsiveness in an experimental model of autoimmunity by using nonmitogenic anti-CD3 monoclonal antibody.

Autoimmune diseases can be characterized by increases in Th cell activities, suggesting that inhibition of Th cell function might ameliorate autoimmunity. We have recently reported that administration of nonmitogenic anti-CD3 mAb (nmCD3) to nonautoimmune mice can induce long-term Th cell hyporesponsiveness, reflected by reduced IL-2 secretion upon re-exposure to Ag. This study was designed to determine the effects of nmCD3 on autoimmunity by using the murine collagen-induced arthritis model. Treatment of DBA/1 mice with nmCD3 delayed the onset and reduced the severity of arthritis in mice immunized with type II collagen (CII). This effect was not caused by depletion of T cells or modulation of TCR. The observed inhibition of arthritis was not caused by decreased Ab production, as anti-CII titers were not affected. Rather, lymph node cells from CII-immunized mice treated with nmCD3 were hyporesponsive to in vitro stimulation with CII. This hyporesponsiveness was reflected by a marked decrease in secretion of IL-2 and IFN-gamma, but not of IL-4, which suggests that nmCD3 had its principal effect on Th1 cells. The hyporesponsiveness was not Ag-specific, because IL-2 and IFN-gamma production in response to a pan-T cell mitogen was also reduced. These results demonstrate that induction of Th1 cell hyporesponsiveness with nmCD3 can significantly alter the course of CIA and suggest that IL-2 and/or IFN-gamma play a crucial role in disease pathogenesis.

Animals↗