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Biomedical subjects

C Hughes

Publications and source records attributed to C Hughes.

At least 235 records · Page 13Linked to original sources

Independent performance among individuals with mental retardation: promoting generalization through self-instruction.

The full participation of individuals with mental retardation in the community requires performance of newly acquired skills in novel circumstances and across the varying demands characteristic of life in the everyday world. For example, a person who has learned how to ride a bus may have to adapt to changes in scheduling, bus routes, or fares. Or an employee who has been taught by a coworker to make salads in a fast-food restaurant will need to continue to complete orders when the coworker no longer is present. Although skill generalization is an implicit educational goal, instructional strategies rarely are employed to influence the attainment of this goal (Haring & Laitinen, in press). Self-instruction is a strategy that has been effective in promoting the independent performance of people with mental retardation. Self-instruction provides individuals with the means for guiding their own behavior in novel situations not associated with training and after assistance has been withdrawn. For example, by using self-instruction, people with mental retardation have learned, among other skills, to sequence their tasks, increase their rate of production, and solve work-related problems. This chapter evaluated studies that investigated use of self-instruction among individuals with mental retardation in community settings. The focus of the review was on identification of factors relating to generalization across people, situations, tasks, and time. The combination of these factors suggests a model for promoting independent performance among individuals with mental retardation. This model combines self-instruction with teaching multiple exemplars and comprises the following six steps: (a) Select an array of examples (responses) an individual is likely to be required to perform in an environment (step 1); (b) classify responses into teaching sets based upon a functional analysis (step 2); (c) divide items of each set into responses that will serve as training examples and those that will serve as generalization probes (step 3); (d) teach trained examples using self-instruction (step 4); (e) evaluate effect of training on trained and untrained examples (i.e., generalization probes) as well as verbalized self-instructional statements (step 5); and (f) withdraw training based upon performance criteria while evaluating the effect of withdrawal (step 6). These steps represent the best practices for promoting independent performance of individuals with mental retardation in the community.

Attention↗

Lymphocyte migration into brain modelled in vitro: control by lymphocyte activation, cytokines, and antigen.

Factors controlling lymphocyte adhesion to brain endothelium were investigated in vitro. Mitogen activation of lymphocytes causes increased adhesion to endothelium, which is maximal at 7-24 hr, declines to normal levels after the cells divide, and requires protein synthesis. Rat brain endothelium can be stimulated with IFN-gamma to increase its adhesion to either normal or activated lymphocytes. The endothelium is sensitive to low levels of cytokine: adhesion develops rapidly after stimulation and requires new protein synthesis. Antigen-specific line cells also adhere more effectively to endothelium than normal lymph node cells. This is enhanced by IFN-gamma treatment of the endothelium and is further increased marginally in the presence of the cognate antigen. The results suggest that either local stimulation of endothelium with cytokines or lymphocyte activation in the periphery will modulate lymphocyte traffic into brain.

Animals↗

Immunoreactive atrial natriuretic peptide in the thyroid gland.

Human thyroid follicles and primary cell cultures derived from them demonstrated atrial natriuretic peptide (ANP)-like immunoreactivity when stained with a monoclonal antibody raised against rat alpha-ANP (ANP 1-28). In thyroid sections the staining was most intense in the tall cuboidal epithelium of small follicles. The intracellular distribution of immunoreactive (ir)-ANP in primary cultures of thyroid follicular cells consisted of discrete granules with a largely perinuclear distribution. The granule density increased with time in culture but was unaffected by exogenous ANP, suggesting an intrinsic synthesis of the immunoreactivity. Thyroid stimulating hormone (TSH; thyrotropin) failed to alter the distribution of ir-ANP after either short-term (6 h) or long-term (1-12 day) exposure. Epinephrine or norepinephrine treatment, however, caused a reduction in the ir-ANP granularity compared with controls in what might represent a stimulated release of the immunoreactivity. The present results suggest that the peptide ANP coexists with thyroid hormones in follicular cells and that the two endocrine activities might be under separate control mechanisms.

Antibodies, Monoclonal↗

A spinal mechanism of action is involved in the antinociception produced by the capsaicin analogue NE 19550 (olvanil).

We have studied the effect of NE 19550 (olvanil, N-(4-hydroxy-3-methoxyphenyl) methyl-9Z-octadecenamide), a capsaicin analogue with approximately equipotent antinociceptive activity in vivo compared with capsaicin, on nociceptive responses recorded from spinal dorsal horn neurones in vivo and from a spinal ventral root in vitro. In adult rats anaesthetized with halothane, antinociceptive doses of olvanil (20-40 mumol/kg, s.c.) reduced C-fibre responses evoked in wide dynamic range, lumbar dorsal horn neurones, by peripheral transcutaneous electrical stimulation. Intradermal injection of olvanil, localized to a discrete region of the peripheral receptive field, did not activate C-fibres nor change C-fibre evoked activation of dorsal horn neurones. Spinal intrathecal administration of olvanil attenuated C-fibre evoked responses and, at the highest concentration, significantly reduced A beta-fibre evoked activity. In the neonatal rat spinal cord/tail preparation maintained in vitro, superfusion of the cord with olvanil (500 nM-5 microM) did not evoke a depolarization but responses to peripheral noxious stimulation were attenuated. In a similar in vitro preparation of the neonatal rat spinal cord, the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was measured in spinal cord superfusates. Capsaicin (2-10 microM) evoked a large release of CGRP-LI but olvanil (2-10 microM) produced only a small or undetectable release. Following the administration of each substance, however, the release of CGRP-LI evoked by a depolarizing potassium stimulus was significantly attenuated. These data indicate that C-fibre input to the dorsal horn was attenuated by acute systemic doses of olvanil that were antinociceptive in behavioural tests. This effect was unlikely to be due to impairment of C-fibre function by a peripheral locus of action but was more consistent with an action in the spinal cord in which the reduced release of a neurotransmitter substance from afferent nerve terminals may play a prominent role.

Animals↗

Characterization of a primate model of hypertension. The response of hypertensive and normotensive male vervets (Cercopithecus aethiops) to cold pressor stress, captopril administration, and acute bolus of atrial natriuretic factor.

In feral populations of African green monkeys or vervets (Cercopithecus aethiops), between 5 and 15% of adults have spontaneously elevated blood pressure (BP). We report here the initial biological and pharmacological characterization of this potential animal model of hypertension. Captive male monkeys with elevated systolic pressures show a modest pressure increase in response to stressors such as capture, phlebotomy and cold challenge. Acute captopril administration lowers BP in monkeys with high blood pressure (HBP), but has no effect on BP in control animals. Furosemide does not acutely reduce BP. Animals with elevated BPs have lower levels of angiotensin II than do age- and weight-matched controls. An acute infusion of atrial natriuretic factor (ANF) diminishes BP and stimulates urinary output in control and HBP vervets. However, both effects are more pronounced in animals with HBP. Heart rate is not affected by any of the experimental manipulations. Taken together, these data suggest that African green monkeys with spontaneously elevated BP may be a useful experimental model for particular types of human hypertension. Additional studies are required to complete the endocrine and pharmacological characterization of individual animals with HBP.

Analysis of Variance↗

Treatment of acute exacerbations of chronic obstructive airways disease--a comparison of amoxycillin and ciprofloxacin.

Ciprofloxacin and amoxycillin were compared in the treatment of acute exacerbations of chronic obstructive airways disease. One hundred and forty patients were evaluable for overall outcome: 60 patients' sputum specimens yielded positive bacteriological cultures. The predominant pathogens were Haemophilus influenzae (43.3%) and Streptococcus pneumoniae (25.0%). Both regimens were safe and produced few adverse effects. An independent observer judged ciprofloxacin to produce a 91.8% success rate (complete success 21.9%; partial success 69.9%) whilst a 73.1% rate (complete success 10.4%; partial success 62.7%) was seen with amoxycillin.

Amoxicillin↗

Isolation of the Actinobacillus pleuropneumoniae haemolysin gene and the activation and secretion of the prohaemolysin by the HlyC, HlyB and HlyD proteins of Escherichia coli.

The gene encoding the c. 105 kD secreted haemolysin protein of the porcine pathogen Actinobacillus pleuropneumoniae serotype 1 has been isolated by screening a lambda gt11 expression library in Escherichia coli with antiserum raised against the wild-type protein. A derivative recombinant DNA pJFF702 expressed the hlylA haemolysin gene from the pUC19 lac promoter but the resulting haemolysin I protein remained within the E. coli cell and was haemolytically inactive. Export of the intracellular A. pleuropneumoniae prohaemolysin out into the medium was achieved by the presence in trans of the E. coli haemolysin secretion genes hlyB and hlyD, and high levels of intracellular haemolytic activity were attained similarly by the E. coli post-translational haemolysin activator gene, hlyC. Southern hybridization of A. pleuropneumoniae parental DNA nevertheless indicated only a low degree of nucleotide sequence identity to the haemolysin structural and secretion genes hlyA and hlyB of E. coli. The data show that despite substantial nucleotide sequence divergence the A. pleuropneumoniae serotype 1 haemolysin determinant is closely related to that which is dispersed throughout other Gram-negative human and animal pathogens.

Actinobacillus↗

HlyB-dependent secretion of hemolysin by uropathogenic Escherichia coli requires conserved sequences flanking the chromosomal hly determinant.

The synthesis and secretion of hemolysin (HlyA) by Escherichia coli are governed by four contiguous genes (hlyCABD) that are closely conserved on plasmids and, among human pathogenic strains, on the chromosome. We have previously shown that in plasmid pHly152 the coexpressed synthesis and export functions are uncoupled by intraoperon transcription termination, which is in turn alleviated by antitermination dictated in cis by a region upstream of the hly operon. In this study we describe an analogous region of ca. 1,100 base pairs flanking the chromosomal hly determinant of the uropathogenic strain E. coli 2001. This region had no significant effect on intracellular levels of hemolysin but activated strongly, both in cis and in trans, the specific hlyB-hlyD-dependent hemolysin secretion function. The secretion-activating region increased the transcription of the secretion gene hlyB, but the transcription effect was not as pronounced as that seen in the pHly152 determinant and was not evident when the region was present in trans to the hemolysin genes, suggesting that, in addition to transcriptional activation, the region may possibly exert a secondary posttranscriptional influence. Southern hybridizations with the 1,100-base pairs secretion-activating sequence showed low identity to plasmid pHly152 and no identity with total DNA from nonhemolytic uropathogenic E. coli or hemolytic isolates of Proteus vulgaris, Proteus mirabilis, and Morganella morganii. In contrast, hybridization to total DNA from hemolytic E. coli isolates belonging to different serotypes showed strong conservation of the activating sequence, indicating that it is an integral component of the chromosomal hly determinant that is widespread among uropathogenic E. coli.

Blotting, Southern↗

Association of country, sex, social class, and life cycle to locus of control in western European countries.

Relatively few studies have focused on causal factors in the development of locus of control. Here nine western European countries are studied to assess the hypothesis that the society in which one lives is important in the scores on locus of control. The data indicate greater variation resulting from country of residence on locus of control than that from the variables of life cycle, sex, and social class. Findings regarding these latter variables are congruent with previous research. In addition, being single was related to having an external locus of control.

Adolescent↗

I.v. therapy: the legislative and regulatory arena.

The inclusion of home IV drug therapy in the Medicare Catastrophic Coverage Act of 1988 brought IV therapy issues to the attention of regulators and providers. Although the legislation was revoked, the issues that were raised in its development must be addressed under the current programs and in any future home IV therapy legislation.

Aged↗

The influence of link protein stabilization on the viscometric properties of proteoglycan aggregate solutions.

The dynamic, steady-shear and transient shear flow properties of precisely prepared link-stable (s0 136, 66% aggregate) and link-free (s0 93, 59% aggregate) proteoglycan aggregate solutions at concentrations ranging from 10 to 50 mg/ml were determined using a cone-on-plate viscometer in a mechanical spectrometer. All proteoglycan solutions tested possessed: (1) linear viscoelastic properties - as measured by the dynamic complex modulus under small amplitude steady oscillatory conditions (1 less than or equal to omega less than or equal to 100 rad/s) - and (2) nonlinear shear-rate dependent apparent viscosities and primary normal stress difference under steady shearing conditions (0.25 less than or equal to gamma less than or equal to 250 s-1). Our transient flow data show that all proteoglycan aggregate solutions exhibited transient stress overshoot effects in shear stress and normal stress. From these steady and transient flow data, we conclude that link protein stabilized aggregates have significant effects on their dynamic and steady-shear properties as well as transient flow properties. The transient stress overshoot data provide a measure of the energy per unit volume of fluid required to overcome the proteoglycan networks in solution from a resting state. Thus we found that link-stable aggregates form much stronger networks than link-free aggregates. This is corroborated by the fact that link-stable aggregates form more elastic (lower than delta) and stiffer (higher [G*]) networks than link-free aggregates. The complete spectrum of viscometric flow data is entirely compatible with the proposed role of link protein in adding structural stability to the proteoglycan-hyaluronate bond. In cartilage, the enhanced strength of the networks formed by link-stable aggregates may play an important role in determining the material properties of the tissue and thereby contribute to the functional capacity of cartilage in diarthrodial joints.

Animals↗

Treatment of cataplexy in a dog with narcolepsy.

A 1-year-old female Rottweiler with a history of narcolepsy and cataplexy lost weight and became worse when given cholinergic agents and/or prednisolone over a 12-day period. The dog was then treated with imipramine HCl, and has been almost clinically normal for 2 years.

Animals↗

Isolation and analysis of the C-terminal signal directing export of Escherichia coli hemolysin protein across both bacterial membranes.

We have studied the C-terminal signal which directs the complete export of the 1024-amino-acid hemolysin protein (HlyA) of Escherichia coli across both bacterial membranes into the surrounding medium. Isolation and sequencing of homologous hlyA genes from the related bacteria Proteus vulgaris and Morganella morganii revealed high primary sequence divergence in the three HlyA C-termini and highlighted within the extreme terminal 53 amino acids the conservation of three contiguous sequences, a potential 18-amino-acid amphiphilic alpha-helix, a cluster of charged residues, and a weakly hydrophobic terminal sequence rich in hydroxylated residues. Fusion of the C-terminal 53 amino acid sequence to non-exported truncated Hly A directed wild-type export but export was radically reduced following independent disruption or progressive truncation of the three C-terminal features by in-frame deletion and the introduction of translation stop codons within the 3' hlyA sequence. The data indicate that the HlyA C-terminal export signal comprises multiple components and suggest possible analogies with the mitochondrial import signal. Hemolysis assays and immunoblotting confirmed the intracellular accumulation of non-exported HlyA proteins and supported the view that export proceeds without a periplasmic intermediate. Comparison of cytoplasmic and extracellular forms of an independently exported extreme C-terminal 194 residue peptide showed that the signal was not removed during export.

Amino Acid Sequence↗

Coronary artery bypass surgery--impact upon the patient's spouse.

The spouses of 65 coronary artery bypass graft surgery (CAGS) patients were assessed to determine levels of psychological symptoms and social impairment both before and 12 months after surgery. There was substantial psychological morbidity in spouses pre-operatively, with from one-third to one-half having clinically significant levels of depression and/or anxiety symptoms. Pre-operatively there was also significant global psychosocial impairment in the spouse. Of the specific domains of psychosocial adjustment, recreational and psychological adjustment was most severely affected, vocational/domestic adjustment and sexual adjustment being less impaired, and extended family relationships showing minimal impairment. There was significant improvement in spouses' psychological and global psychosocial adjustment at 12 months, with recreational adjustment showing the greatest improvement. Significant improvements also occurred in vocational adjustment but not in domestic or sexual adjustment. Neither physical, psychological nor social adjustment variables preoperatively in either the patient or spouse were predictive of psychological morbidity in the spouse (anxiety or depression) at 12 months. Similarly there were no significant patient or spouse preoperative predictors of social adjustment in the spouse at 12 months. However, the patients post-operative psychological morbidity and the spouses social and psychological morbidity were related.

Adult↗

A prospective evaluation of the psychosocial effects of coronary artery bypass surgery.

Eighty-nine patients were prospectively studied to determine psychological and psychosocial impairment prior to and after coronary artery graft surgery (CAGS). Psychological morbidity prior to surgery was high, with one-third having clinically significant levels of depression and/or anxiety symptoms. Scores on the Psychosocial Adjustment to Illness Scale indicated a generally high level of psychosocial impairment pre-operatively, with vocational and domestic functioning being most severely affected, social and sexual functioning being less impaired, and extended family relationships being largely unaffected. In general, there was a significant reduction in psychological morbidity and an improvement in psychosocial functioning at 6 months, which remained at 12 months. Vocational and domestic functioning showed the greatest improvement. Sexual and social functioning showed modest improvements overall, with significant numbers reporting residual impairment due to their heart disease. These findings add to a growing body of evidence demonstrating generally favourable psychological and social outcome following CAGS.

Adaptation, Psychological↗

Transcription antitermination in an Escherichia coli haemolysin operon is directed progressively by cis-acting DNA sequences upstream of the promoter region.

Export of haemolysin protein (HlyA) directed by the Escherichia coli pHly152 hly determinant is dependent upon transcriptional activation, primarily strong intraoperon transcript antitermination imposed between the haemolysin structural genes hlyC and hlyA and the contiguous downstream export genes hlyB and hlyD. Transcript elongation was dictated by a DNA sequence several kb upstream of the rho-independent terminator but could not be assigned to a discrete locus; on the contrary, it was progressive, increasing with the addition of up to 3.5 kbp of operon-proximal sequence containing the insertion elements IS2 and IS91. Antitermination was prominent throughout logarithmic growth but absent in stationary phase, and was effective only in cis but not in trans. Primer extension indicated that transcription activation utilized the native transcriptional start sites of the unactivated hly operon.

Base Sequence↗