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Biomedical subjects

S Baldwin

Publications and source records attributed to S Baldwin.

At least 37 records · Page 2Linked to original sources

Efficient adenoviral-mediated murine neonatal small intestinal gene transfer is dependent on alpha(v) integrin expression.

BACKGROUND/PURPOSE: Clinical application of gene therapy for patients who have inflammatory bowel disease or short bowel syndrome will require the development of new strategies to improve the efficiency of small intestinal gene transfer. Previously, the authors developed a method for adenoviral-mediated small intestinal gene transfer in vivo in neonatal and adult mice. The present study evaluates the hypothesis that the integrins alpha(v)beta3 and alpha(v)beta5, the secondary receptors for adenoviral internalization, play a facilitative role in neonatal murine adenoviral-mediated small intestinal gene transfer. METHODS: Immunohistochemical techniques identified the integrin alpha(v)beta3 and the integrin subcomponents alpha(v), beta3, and beta5 in neonatal and adult small intestine. The effects of integrin receptor antagonists on transgene expression was also studied in our neonatal model of adenoviral-mediated small intestinal gene transfer in vivo. RESULTS: Gene transfer was significantly decreased by the addition of integrin receptor antagonists versus control peptide. Integrin alpha(v)beta3 and integrin subcomponent alpha(v), beta3, and beta5 are expressed in neonatal and adult small intestine. Integrin antagonists administered simultaneously blocked efficient adenoviral-mediated neonatal small intestinal gene transfer in vivo compared with control peptide. CONCLUSION: Strategies to upregulate integrin expression may improve adenoviral-mediated small intestinal gene transfer.

Adenoviruses, Human↗

The Whiplash Shaken Infant Syndrome: has Caffey's syndrome changed or have we changed his syndrome?

OBJECTIVE: The aim of this study is to examine the data used by John Caffey in his description of the Whiplash Shaken Infant Syndrome and compare it with recent data in an attempt to determine whether the syndrome that he described has changed, or if we have changed his syndrome into what we now call The Shaken Infant Syndrome. METHOD: This study examined recent literature describing the Shaken Infant Syndrome, and compared it to Caffey's descriptions. In addition, a retrospective review of 71 children under the age of 3 years identified as having a subdural hematoma caused by other than accidental means during 54 months was done. This data was compared to data from the 27 case examples offered by Caffey in 1972 and his other descriptions in 1974 and 1946. RESULTS: A review of recent literature shows that our definition of Shaken Infant Syndrome today includes cases where impact trauma was involved. In contrast to Caffey's descriptions, we found the perpetrator to be more often male, fractures to be more often to ribs rather than long bones, and admissions of shaking and other trauma more often made. CONCLUSIONS: Our findings demonstrate that not only have we changed the diagnostic parameters from Caffey's original Whiplash Shaken Infant Syndrome, but the syndrome has also changed to reflect changes in medical diagnosis and in our society.

Brain Injuries↗

A clinical method for testing the safety of catamenial pads.

Methods are described for assessing the gynecologic, dermatologic, and microbiologic effects of deodorant and non-deodorant catamenial pad use over a 6-month period. A controlled, randomized, investigator-blind parallel study was conducted with 190 women between the ages of 18 and 45 years. Data on medical histories, physical examinations, diagnostic laboratory tests, gynecologic and dermatologic examinations and microbiology were collected. No significant differences in gynecologic, dermatologic, or microbiologic parameters were observed between control and treated groups, and no pad-related adverse health effects were observed in this clinical study.

Adolescent↗

Immunogenicity and protective efficacy of a tuberculosis DNA vaccine.

Tuberculosis is the most widespread and lethal infectious disease affecting humans. Immunization of mice with plasmid DNA constructs encoding one of the secreted components of Mycobacterium tuberculosis, antigen 85 (Ag85), induced substantial humoral and cell-mediated immune responses and conferred significant protection against challenge with live M. tuberculosis and M. bovis bacille Calmette-Guérin (BCG). These results indicate that immunization with DNA encoding a mycobacterial antigen provides an efficient and simple method for generating protective immunity and that this technique may be useful for defining the protective antigens of M. tuberculosis, leading to the development of a more effective vaccine.

Animals↗

Characterization of recombinant extracellular domain of human interleukin-10 receptor.

The extracellular region of the human interleukin-10 (hIL-10) receptor was expressed using a myeloma cell line and was purified to homogeneity by ligand-affinity chromatography. SDS-polyacrylamide gel electrophoresis analysis indicated that the soluble receptor is glycosylated and has an apparent molecular mass of 35,000-45,000. Under native conditions, soluble hIL-10 receptor was determined by gel filtration to be a monomeric protein. Soluble hIL-10 receptor was able to inhibit the binding of 125I-hIL-10 to the full-length receptor and was able to antagonize the effect of human IL-10 in cell proliferation and cytokine synthesis inhibition. The apparent dissociation constant (Kd) of soluble hIL-10 receptor was determined to be 563 +/- 59 pM, approximately 2- to 10-fold higher than that found on intact cells (Tan, J. C., Indelicato, S. R., Narula, S. K., Zavodny, P. J., and Chou, C.-C. (1993) J. Biol. Chem. 268, 21053-21059; Liu, Y., Wei, S. H.-Y., Ho, A. S.-Y., de Waal Malefyt, R., and Moore, K. W. (1994) J. Immunol. 152, 1821-1829). When hIL-10 binds soluble hIL-10 receptor in solution, a single complex was detected by gel filtration, and the complex was found to consist of two hIL-10 dimers and four soluble receptor monomers, suggesting that hIL-10 may induce a novel mode of oligomerization of the receptor upon binding.

Amino Acid Sequence↗

Second and early third trimester atrial natriuretic peptide (ANP) levels in pregnancies subsequently complicated by hypertension.

OBJECTIVE: To explore the clinical utility of measuring atrial natriuretic peptide (ANP) in the second and early third trimesters of pregnancy in order to predict pregnancy induced hypertension (PIH). METHODS AND MATERIALS: The study was done in a University Teaching Hospital. A prospective study of 200 women in their first pregnancy was conducted. ANP was measured at 2 gestational windows, 20-26 weeks and 30-34 weeks. This was correlated with pregnancy outcomes, in particular PIH. Student's t-test was used to compare ANP levels between women who developed PIH and those who did not. The receiver operator curve (ROC) was used to determine its clinical utility. RESULTS: ANP levels were lower at 20-26 weeks in women who subsequently developed PIH but there was no significant difference at 30-34 weeks between women who had normotensive pregnancies and those who later developed PIH. The character of the ROC would indicate that it is not useful for prediction. CONCLUSION: ANP levels in the second and early third trimesters has limited clinical utility for the prediction of PIH.

Adult↗

Electroconvulsive therapy, children and adolescents: the power to stop.

The administration of electroconvulsive therapy (ECT) to children and adolescents remains an unresolved area of clinical debate for nurses. Thus, some nurses have refused to participate in the treatment of minors with ECT, invoking codes of conduct to justify their actions. Other nurses have supported the use of ECT with children and adolescents, via provision of technical assistance to medical colleagues. A cross-national comparison of ethical codes of conduct has confirmed that nurses should take decisive action in the clinical arena when the needs or rights of vulnerable minors are compromised. The provision of clinical guidelines is suggested as one method to enshrine the rights of at-risk children and adolescents.

Adolescent↗

Preliminary investigation: Brief Screening Interview (BSI) with young drinking offenders.

A pilot Brief Screening Interview (BSI) was introduced in three settings. These included court-referred offenders, court-processed offenders, and offenders apprehended by police officers. The settings included two urban centres and one rural location in the UK. The BSI was introduced as one method to increase uptake of services by young drinking offenders in the criminal justice system. As a low-cost intervention, the BSI can be delivered by a range of personnel in different locations. Examination of preliminary results has demonstrated the BSI as a promising new method of initial assessment of offenders in the criminal justice system.

Adolescent↗

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning.

Neural-cell adhesion molecules (N-CAMs) are members of the immunoglobulin superfamily mediating homo- and heterophilic cell-cell interactions. N-CAM exists in various isoforms which are generated by alternative splicing. During embryonic development, N-CAMs are expressed in derivatives of all three germ layers, whereas in the adult animal they are predominantly present in neural tissue. Processes like neurulation, axonal outgrowth, histogenesis of the retina and development of the olfactory system are correlated with the regulated expression of N-CAMs. We show here that N-CAM-deficient mice generated by gene targeting appear healthy and fertile, but adult mutants show a 10% reduction in overall brain weight and a 36% decline in size of the olfactory bulb. N-CAM deficiency coincides with almost total loss of protein-bound alpha-(2,8)-linked polysialic acid, a carbohydrate structure thought to be correlated with neural development and plasticity. The animals showed deficits in spatial learning when tested in the Morris water maze, whereas activity and motor abilities appeared normal.

Animals↗

Low-volume microwave digestion of marine biological tissues for the measurement of trace elements.

The use of low-volume (7 ml) Teflon vessels and microwave heating is described for the digestion of three marine biological tissues representing a mollusc, a fish and a crustacean. Freeze-dried samples (< 0.1 g dry mass) and 1 ml of nitric acid were placed in 7 ml screw-topped Teflon vessels and treated using a programmed three-stage digestion. The first two stages were kept consistent (600 W, 2 min; 0 W, 2 min) and the third stage was varied from 150 to 450 W over 15-60 min to find the optimum microwave digestion conditions. Trace elements were determined using flame atomic absorption spectrometry, or electrothermal atomic absorption spectrometry when analysing samples containing very low concentrations of cadmium. Quantitative recoveries of copper, zinc and cadmium were obtained from the five marine reference materials under the following conditions: 600 W, 2 mins; 0 W, 2 min; 450 W, 45 mins.

Animals↗

Disulfide bond assignments and secondary structure analysis of human and murine interleukin 10.

Interleukin 10 (IL-10), which was first discovered by its ability to inhibit the synthesis of various cytokines, most notably gamma interferon, from Th1 helper cells, displays pleiotropic immunoregulatory properties. Human and murine IL-10 have a high amino acid sequence identity (ca. 73%) which includes the conservation of all four cysteine residues in human IL-10 and the first four out of five cysteine residues for murine IL-10. Chemical analysis was used to determine that both recombinant human and recombinant murine IL-10 contain two disulfide bonds. The disulfide pairs for each were determined by mass spectrometric and reversed-phase HPLC analysis of trypsin-derived polypeptide fragments. The disulfide bond assignments for both species were similar in that the first cysteine residue in the sequence paired with the third and the second paired with the fourth. The fifth cysteine in murine IL-10 was determined by chemical modification to be unpaired. Far-UV circular dichroism analysis indicated that the secondary structure of recombinant human and murine IL-10 are composed of ca. 60% alpha-helix. Reduction of the disulfide bonds structurally destabilized the protein and led to a structure containing only 53% alpha-helix. The reduced protein displayed no in vitro biological activity in a mast cell proliferation assay. These studies indicate that IL-10 is a highly alpha-helical protein containing two disulfide bonds, either one or both of which are critical for its structure and function. In addition, these properties suggest that this interesting cytokine may belong to the alpha helical cytokine class of hematopoietic ligands.

Amino Acid Sequence↗

A homology model of human interferon alpha-2.

An atomic coordinate five alpha-helix three-dimensional model is presented for human interferon alpha-2 (HuIFN alpha 2). The HuIFN alpha 2 structure was constructed from murine interferon beta (MuIFN beta) by homology modeling using the STEREO and IMPACT programs. The HuIFN alpha 2 model is consistent with its known biochemical and biophysical properties including epitope mapping. Lysine residues predicted to be buried in the model were primarily unreactive with succinimidyl-7-amino-4-methylcoumarin-3-acetic acid (AMCA-NHS), a lysine modification agent, as shown by mass spectrometric analysis of tryptic digests. N-terminal sequence analysis of polypeptides generated by limited digestion of HuIFN alpha 2 with endoproteinase Lys-C demonstrated rapid cleavage at K31, which is consistent with the presence of this residue in a loop in the proposed HuIFN alpha 2 model. Based on this model structure potential receptor binding sites are identified.

Amino Acid Sequence↗

Preparing the advanced practitioner in learning disabilities nursing.

This paper aims to describe the practical, therapeutic and educational dimensions of professional preparation in the field of Learning Disabilities Nursing. Through an exploration of the primary, secondary and tertiary dimensions of care, the authors identify the range of skills and competencies which they consider necessary for the achievement of advanced practice in this specialist field. Arguments are proposed which demonstrate the essential and continuing role of the nurse through a consolidation of the three dimensions of care. In so doing, an educational foundation for advanced practice which enables the nurse to work effectively within present and future health and social care initiatives is proposed.

Clinical Competence↗

The influence of a glucose load on subsequent carbohydrate metabolism in pregnancy.

Two separate independent exercises comparing 50 g with 75 g and 100 g oral glucose tolerance tests (OGTT) were performed in Chinese pregnant women. We found a significant difference in fasting values between the paired OGTTs when the 100 g test preceded the 50 g test. The fasting glucose levels on the second occasion of testing were significantly lower than on the first testing. The difference was less pronounced when the first glucose load was 75 g and was insignificant when the 50 g test was given first. The blood glucose response to glucose loads was also significantly altered on the second occasion of testing, again in proportion to the size of the first glucose load. We postulate that this influence of glucose tolerance testing on subsequent carbohydrate metabolism results either from sensitization of the pancreatic islet cells or from sensitization of tissues, resulting in increased rate of glucose utilization. We also suggest that an 1,800 Kcal diet represents an increase in carbohydrate load over their normal diet for many of our patients. In patients with mildly deranged OGTT, improvement in the glucose profile on diet may be due to this phenomenon rather than to a decrease in carbohydrate as is believed.

Asian People↗

Insulin-like growth factor-binding protein-1, glucose tolerance and fetal growth in human pregnancy.

Two hundred Chinese primigravidae had 50 g 3-h oral glucose tolerance tests (OGTTs) twice in pregnancy; between 20 and 24 weeks and between 30 and 34 weeks of gestation. In 149 women, a single sample was taken for insulin-like growth factor-binding protein-1 (IGFBP-1) measurement 0, 1, 2 or 3 h after the glucose load at both visits; in 55 women IGFBP-1 levels were estimated in all four OGTT samples. Fetal growth was assessed by ultrasound performed at the first and second visit and, if possible, at term, and by anthropometry of the neonate. Cord serum IGFBP-1 was measured in 144 of the babies. Mothers who developed gestational diabetes were excluded. Maternal levels of IGFBP-1 were inversely related to glucose levels at 0, 1 and 2 h in the third trimester of pregnancy. IGFBP-1 measured at 1 h in an OGTT increased between the second and third trimester. There was an inverse correlation between maternal IGFBP-1 measured in the second trimester and all fetal measurements at that time, and with most neonatal measurements and birthweight. Levels of IGFBP-1 in the third trimester were inversely correlated to neonatal abdominal circumference, skinfold thickness and birthweight. Cord blood IGFBP-1 was inversely related to growth of abdominal circumference. The strongest inverse relationship was between IGFBP-1 and maternal weight. Fasting glucose in the second trimester was positively correlated to fetal subcutaneous fat and growth of abdominal circumference. In the third trimester it was related to fetal abdominal circumference, the growth of abdominal circumference, birthweight and neonatal skinfold thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗