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Biomedical subjects

S Wade

Publications and source records attributed to S Wade.

At least 37 records · Page 2Linked to original sources
PubMed1996

A One-Bead One-Peptide Combinatorial Library Method for B-Cell Epitope Mapping

The one-bead one-peptide combinatorial library method represents a powerful approach to the discovery of binding peptides for various macromolecular targets. It involves the synthesis of millions of peptides on beads such that each bead displays only one peptide entity. The peptide-beads that interact with a specific macromolecular target are then isolated for structure determination. We have applied this method to discovering peptide ligands for several murine monoclonal antibodies: (i) anti-beta-endorphin (continuous epitope), (ii) anti-vmos peptide, (iii) anti-human insulin (discontinuous epitope), and (iv) surface immunoglobulins (μkappa) of two murine B-cell lymphoma cell lines (antigen unknown).

Journal Article↗
PubMed1995

Library of libraries: approach to synthetic combinatorial library design and screening of "pharmacophore" motifs.

Construction of synthetic combinatorial libraries is described that allows for the generation of a library of motifs rather than a library of compounds. Peptide libraries based on this strategy were synthesized and screened with model targets streptavidin and anti-beta-endorphin antibody. The screens resulted in observation of expected motifs providing evidence of the effectiveness of the suggested approach.

Amino Acid Sequence↗
PubMed1995

Application of a dual color detection scheme in the screening of a random combinatorial peptide library.

Selectide Technology is a random synthetic combinatorial library method in which millions of random compounds are screened in parallel for their ability to bind to a tagged macromolecular target. The library consists of millions of beads and each individual bead expresses a unique chemical compound such as a peptide. In the standard enzyme-linked colorimetric detection scheme, the positive bead which turns color is isolated for microsequencing. In this paper, a dual color detection scheme using two sequential orthogonal probes is described. This dual color system enables one to rapidly differentiate false positive beads from true positive beads, resulting in a much more efficient use of the microsequencer.

Amino Acid Sequence↗
PubMed1995

Relationship of 24-hour urinary free cortisol to 4-hour salivary morning and afternoon cortisol and cortisone as measured by a time-integrated oral diffusion sink.

The relationship between salivary corticosteroids integrated over 4-hour periods and urinary free cortisol collected over 24 hours was investigated in normal controls. Twenty-one normal volunteers wore "oral diffusion sink" sampling devices in their mouths for two 4-hour periods (08:00-12:00 hours and 13:00-17:00 hours) and on the same day collected a 24-hour urine specimen. Time-integrated salivary corticosteroid concentrations were determined from the sample devices and urinary free cortisol was measured. Salivary corticosteroids were not consistently higher in the morning than in the afternoon period and did not differ between men and women. Urinary free cortisol levels were higher in women. No salivary corticosteroids measure was significantly correlated with urinary free cortisol. We conclude that time-integrated salivary corticosteroids do not reflect urinary free cortisol levels in normal controls.

Adult↗
PubMed1995

Assessing the effects of traumatic brain injury on family functioning: conceptual and methodological issues.

Reviewed empirical literature published since 1975 on the effects of pediatric traumatic brain injury (TBI) on the family. Few systematic, hypothesis-driven investigations of the impact of TBI on family functioning have been conducted. However, existing findings indicate that severe TBI can adversely affect families and individual family members. Certain factors, such as poor preinjury functioning and parental psychological disorder, appear to place families at greater risk for long-term disruption. Issues associated with the conceptualization of the impact of TBI on various aspects of family functioning are discussed and methodological considerations are outlined. Special attention is given to novel strategies for studying these complex, multifaceted issues. Finally, a framework is proposed for examining the processes of family adaptation after pediatric TBI to guide future research directions.

Adaptation, Psychological↗
PubMed1995

Serum osteocalcin regulation in protein-energy malnourished children.

To evaluate bone turnover changes occurring during protein-energy malnutrition, serum osteocalcin, a marker of bone formation, has been studied in healthy control, stunted, and severely malnourished (kwashiorkor and marasmus) Senegalese children. Serum osteocalcin levels were dramatically reduced in stunted, kwashiorkor, and marasmic children compared with control children. In addition serum osteocalcin levels of control children living in Senegal were lower (-46%) than those of African children living in France. Interestingly, serum osteocalcin level was not related to its major known regulators (1 alpha,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, and PTH) nor to stunting, but was related to serum transthyretin and thyroid hormones concentrations. These data suggest that serum osteocalcin level is related to protein-energy status and that bone formation was affected in apparently healthy and in malnourished Senegalese children. Serum osteocalcin could be a potent tool in the study of the alterations of bone formation in malnutrition.

Child, Preschool↗
PubMed1994

Gentamicin vestibulotoxicity.

We reviewed 36 patients with gentamicin vestibulotoxicity to determine its relationship to gentamicin dosage, serum gentamicin levels, and the development of gentamicin nephrotoxicity. Thirty of the patients had received intravenous or intramuscular gentamicin; six had received intraperitoneal gentamicin. Sixteen of the 30 patients treated with intramuscular or intravenous gentamicin had received less than the recommended maximum dose of 5 mg/kg/day for less than the recommended maximum period of 10 days. Nephrotoxicity as well as vestibulotoxicity developed in 16 of these 30 patients. Gentamicin vestibulotoxicity was not recognized before discharge from hospital in 32 of the 36 patients. We conclude that as far as the vestibular system is concerned there is no safe gentamicin dose and no safe serum gentamicin level, and there is an increased risk of vestibulotoxicity in patients in whom nephrotoxicity develops. Physicians who use gentamicin should become more aware of the clinical features of vestibulotoxicity because stopping gentamicin as soon as symptoms of vestibulotoxicity appear could prevent permanent impairment of vestibular function.

Adult↗
PubMed1994

Association of IBM's "A Plan for Life" health promotion program with changes in employees' health risk status.

To evaluate the association of participation in IBM's "A Plan for Life" program with changes in blood pressure, serum total, high-density lipoprotein, and non-high-density lipoprotein cholesterol, body mass index, and cigarette smoking, we compared changes in these measures over a 1- to 5-year period among program participants and nonparticipants initially found to be at risk. After adjustment for age, sex, time to follow-up, and baseline values, the proportion of participants no longer at high risk was significantly greater than the corresponding proportion of nonparticipants in the areas of blood pressure total and non-high-density lipoprotein cholesterol and smoking cessation.

Adolescent↗
PubMed1994

Growth hormone and insulin-like growth factor I in athletes performing a marathon at 4000 m of altitude.

Human growth hormone (hGH) characteristically increases during physical exercise. In sports medicine, hGH changes have mostly been described in short-term performances under standardized laboratory procedures. We studied hGH and insulin-like growth factor I (IGF-I) under field conditions in 7 runners performing a marathon at 4000 m of altitude, to study the hormonal changes under extreme endurance effort and to evaluate the release of 22 kDa and 20 kDa monomers under these conditions, in comparison with a control group. The blood samples were taken at sea level, after 1 week of acclimatization, immediately after the run, and after a recovery of 24 h from the marathon. hGH was quantified by using a polyclonal method, a 22 kDa specific monoclonal method and a monoclonal method recognizing both 22 kDa and 20 kDa isoforms. A significant increase in hGH was noted using all methods after the marathon, followed by a significant decrease after recovery. Significant differences between athletes and controls were found only for the measurement after the marathon. No statistically reliable decrease of IGF-I was observed in athletes and controls. We obtained more limited hGH rises than previously described in athletes; the importance of lactate levels indicates that the use of physical exercise as a stimulation test for hGH should be closely standardized. The 20 kDa monomer and other hGH molecular forms played a limited role in the hormone increase: in our experience, elevation of hGH in heavy exercise corresponds mostly to the 22 kDa isoform. We suggest that the evaluation of hGH elevation in sports medicine could be accurately performed using specific 22 kDa monoclonal assays.

Adult↗
PubMed1994

[Medico-social problems of young adolescents in Guediawaye (suburban area of Dakar-Senegal)].

A survey in the district of Guediawaye, towards teenagers from 12 to 16 years old, recruited according to a stratified risky method of sampling in 4 different areas has been carried out in order to evaluate their main medico-social problems. It ended up to the following findings: the majority live in hard socio-economic conditions stamping by promiscuity, a weak family income and a low level of education of the parents. 39.2% have been placed under the guardianship of a relative other than the parents. 98.8% do not find spare time structures in their environment. The usage of tobacco and drug is respectively 14% and 1%; 79.4% of students have hardly access to the school stationery, while the teenagers in job apprenticeship have constraints linked to long hours of work (95%). The morbid affections are too varied, dominated by stomach aches (37.8%) far before traumatics (6%); the most frequent therapeutic is resort traditional or empiric treatment. The authors advocate the setting up of a medico-social center making interfere all persons, implied resources in the undertake of the teenagers.

Adolescent↗
PubMed1993

Discovery of D-amino-acid-containing ligands with selectide technology.

When all L-amino acid (aa) random peptide libraries synthesized on solid-phase particles were screened (Selectide Technology), we identified several peptide ligands (YG_F_) that interacted specifically with an anti-beta-endorphin monoclonal antibody (clone 3E7) (single-letter aa symbols; symbols '_' indicate variable aa). Here, we report on the screening of three different D-aa-containing pentapeptide libraries (XxXxX, xXxXx and xxxxx, wherein X = L-aa, and x = D-aa) with the same antibody, in which several D-aa-containing ligands were identified. The binding affinities of many of these D-aa-containing ligands were as least two orders of magnitude lower than that of YGGFL, for which the Ki is 17.5 nM.

Amino Acid Sequence↗
PubMed1993

Discovery of biologically active peptides in random libraries: solution-phase testing after staged orthogonal release from resin beads.

To speed drug discovery, we developed an approach for identification of individual peptides with a desired biological activity from a library containing millions of peptides. The approach uses sequential orthogonal release of chemically synthesized peptides from insoluble beads, followed by testing in solution. In this system, each bead within a library of beads has one peptide sequence, but peptide molecules are attached to the bead with three types of chemical linkers, including two linkers cleavable at different pH optima. An uncleavable linker keeps some peptide attached to the bead for sequencing positives from the solution assay. Applicability of this discovery technique was documented by identifying ligands for a monoclonal antibody and for the human platelet fibrinogen receptor, glycoprotein IIb/IIIa.

Amino Acid Sequence↗
PubMed1993

Endocrine correlates of stress vulnerability.

Psychological stress is implicated as one element in a constellation of risk factors for the development and maintenance of psychosomatic disease. Endocrine responses to stressful experience vary widely among individuals, and may account for some of the individual variability in vulnerability to development of psychosomatic symptoms under stress. Endocrine stress responsiveness probably has a large genetic component, but is also known to be modifiable by prolonged and/or profound stressful experience. Social and cognitive factors influence the pituitary-adrenal response to stress, and sex differences may also be significant. It may be possible to develop specific tests of endocrine responsiveness, perhaps incorporating psychological and pharmacological challenges, that may serve as markers of chronic stress experience or of vulnerability to psychosomatic disorders.

Adjustment Disorders↗
PubMed1992

Cognitive-behavioral treatment of health-impairing food phobias in children.

Three cases reports describe assessment and treatment of three boys (ages 6 to 8 years) hospitalized because of weight loss and malnutrition, caused by severe dietary restriction and/or refusal to eat solid food. Psychological, behavioral, and medical assessments indicated that the boys were of average intelligence, without other significant psychological or medical disorders. Their eating disturbances were conceptualized as phobic disorders maintained by family factors reinforcing the children's avoidant behaviors. Cognitive-behavioral treatment consisted of an individualized combination of contingency management, shaping, desensitization, relaxation training, education, and cognitive restructuring. Generalization and maintenance were promoted by training parents to implement treatment at home before discharge. Treatment positively affected overall caloric intake, weight gain, number of solid foods accepted, and incidence of emesis.

Child↗
PubMed1990

Failure of tryptophan deficiency to reduce specifically serum levels of transthyretin or albumin in rats.

Because transthyretin (TTR) is a tryptophan-rich molecule and a sensitive nutritional marker, tryptophan deficiency might markedly influence the circulating level of TTR. The effect of severe tryptophan (Trp) deficiency on serum TTR, as well as on albumin and transferrin levels, was studied in growing rats for 8 d. The animals were then refed a control diet for 12 d. The Trp-deficient and control diets contained 0.008 and 0.34% Trp, respectively. A loss of body weight and a dramatic reduction in food intake were observed in the Trp-deficient rats. Although serum total Trp concentration was significantly less in these rats than in pair-fed controls, serum TTR declined to the same extent in both groups compared to control rats fed ad libitum. Albumin concentrations were not altered, but transferrin levels declined slightly in the Trp-deficient rats compared to both the pair-fed group and the controls fed ad libitum. Refeeding the control diet to Trp-deficient rats restored total and free Trp concentrations, as well as TTR and transferrin levels, but body weight and food intake remained lower than in the control group. To examine the effect of moderate Trp restriction, rats were fed for 2 wk a diet whose Trp content was 50% less than that of the control diet. Although total and free Trp concentrations were significantly lower in the rats fed the Trp-deficient diet than in the control group, body weight, food intake and TTR levels were similar in both groups. The results suggest that acute and severe Trp deficiency per se does not modify TTR and albumin levels.

Animals↗