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N Simpson

Publications and source records attributed to N Simpson.

15 recordsLinked to original sources

Magnetic resonance imaging of the rat brain following acute carbon monoxide poisoning.

Magnetic resonance (MR) may be used for repeatedly and non-invasively imaging the brain. Until now, no studies have used this approach to study the effects of carbon monoxide (CO) poisoning in a defined animal model. Conscious, Levine-prepared female rats (unilateral carotid artery and jugular vein occlusion) were exposed to 2400 ppm CO for 90 min, with or without the infusion of 50% glucose solution; CO-stimulated increases in blood glucose and lactate occurred in both groups, while blood pressure and body temperature fell. One to four hours following termination of CO exposure, increased cortical pixel intensity, cortical surface area and brain midline shift were observed on the operated side of the brain in some rats of both groups (i.e. responders = R), providing evidence of edema. At sacrifice, 5 h following termination of CO exposure, gross water content was increased on the left side in the corresponding cortical slices in R rats, providing another measure of edema. Significant positive correlations were found between left to right pixel intensity difference and water content difference, and between the extent of midline shift and water content difference. The elevations of blood glucose and lactate concentrations, and the magnitudes of CO-induced hypothermia and hypotension were similar to those in past studies, but appeared to exert no effect on the severity of cortical edema in terms of differences in pixel intensity, surface area, midline shift or gross tissue water content. Thus, the observed differences between the R rats is not explained by the available data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A comparison of two breathing exercise programs for patients with quadriplegia.

This study compared the use of abdominal weights (AbWts) to inspiratory resistive muscle training (IMT) on selected measures of pulmonary function. Eleven patients, aged 16 to 41 years (mean = 27.8, SD = 8.3) with complete cervical injuries were randomly assigned to either an AbWts or IMT treatment group. Subjects in both treatment groups received daily treatments (five times weekly) for 7 weeks. Forced vital capacity (FVC), inspiratory capacity (IC), maximal voluntary ventilation (MVV), peak expiratory flow rate (PEFR), and inspiratory mouth pressure (PImax) were measured weekly. Analysis of variance for repeated measures showed no difference between the AbWts and IMT treatments; there were significant differences within each respective treatment group for all five variables. Although the data did not support the effectiveness of one method of training over the other, the larger increase in MVV with the IMT protocol may be indicative of an endurance training effect with this protocol. Future research should compare the effects of breathing exercise training to spontaneous recovery of the respiratory muscles in control subjects.

Adolescent

Selecting high-affinity binding proteins by monovalent phage display.

Variants of human growth hormone (hGH) with increased affinity and specificity for the hGH receptor were isolated using an improved phage display system. Nearly one million random mutants of hGH were generated at 12 sites previously shown to modulate binding to the hGH receptor or human prolactin (hPRL) receptor. The mutant hormones were displayed in a monovalent fashion from filamentous phage particles as fusions to the gene III product of M13 packaged within each particle. After three to six cycles of enrichment for hGH-phage particles that bound to hGH receptor beads, we isolated hGH mutants that exhibited consensus binding sequences for the hGH receptor. Residues previously identified as important for hGH receptor binding by alanine-scanning mutagenesis were more highly conserved by this selection method. However, other residues nearby were not optimal, and by mutating them, hormone variants having greater affinity and selectivity for the hGH receptor were isolated. This approach should be useful for those who wish to modify and understand the energetics of protein-ligand interfaces.

Amino Acid Sequence

Interaction between flavone acetic acid (LM-975, NSC 349512) and radiation in Glasgow's osteogenic sarcoma in vivo.

Flavone acetic acid (FAA) is a new anticancer agent in Phase II trials in Europe. In preclinical testing FAA showed broad activity against murine solid tumors and minimal activity against murine leukemias. Our interest in studying the combination of FAA and radiation was based on two of its biological effects which might modify radiation damage. First, FAA depletes ATP and inhibits macromolecular synthesis which are needed to repair radiation-induced DNA strand breaks; and second, inhibition of tumor blood flow by FAA could lead to radiobiological hypoxia. Various schedules of FAA (170 mg/kg I.V.) (n = 9, SF = 0.44) and radiation (10 Gy) (n = 9, SF = 0.37) were investigated against s.c. implanted Glasgow osteogenic sarcoma. In the same model we studied both the kinetics of ATP depletion by 31P-Nuclear Magnetic Resonance Spectroscopy and the repair of radiation induced single and double strand breaks by alkaline elution. The combined response was not significantly different from log-additive when radiation was given 24, 5 or 1 hr before FAA. When FAA was given immediately before radiation an increase in tumor response, significantly different from log-additive (p = 0.03) was observed. This enhancement disappeared when radiation was delayed for between 1 and 48 hr after FAA. While decreased ATP levels and increased response to radiation occurred within minutes after FAA administration, no effect of FAA at either 180 or 200 mg/kg was observed on the repair of radiation induced single or double strand breaks (10 and 50 Gy, respectively; 5 hr after FAA) in spite of significant ATP depletion in the tumors.

Adenosine Triphosphate

Unwanted hair.

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Female

Memory assessment using the Strub-Black Mental Status Examination and the Wechsler Memory Scale.

A systematic mental status exam often can differentiate accurately patients with organic brain disease from normal persons and those with functional disorders. The present study attempts to validate the memory portion of the Strub-Black Mental Status Exam by comparing it to the Wechsler Memory Scale. Twenty-five brain-damaged and 25 routine medical patients were given Form I of the Wechsler Memory Scale and the memory portion of the Strub-Black Mental Status Exam at their hospital bedside. Results indicate significant differences in almost all scores between the brain-damaged and normal groups on both the Wechsler Memory Scale and Mental Status exam; the Mental Status Exam differentiated between groups at a higher level of significance of ANOVA and ANCOVA comparisons of total memory scores, as well as several subtests. In these samples, age, more than education, was an important factor that affected memory test performance. The Mental Status Examination appears valid for the differentiation of clinical samples and for the documentation of specific aspects of memory dysfunction in individual brain-damaged patients. This study represents a beginning step in providing normative data on components of the Strub-Black mental status examination.

Adult

Metabolic consequences of atenolol and propranolol in treatment of essential hypertension.

A six-month study of triglyceride, cholesterol, free fatty acid (FFA), glucose, insulin, growth hormone, and glucagon concentrations was carried out in asymptomatic hypertensive normal-weight men randomly allocated to treatment with atenolol or propranolol. A highly significant increase in the basal plasma triglyceride concentration was observed in propranolol-treated patients after three and six months' treatment, with a smaller but significant increase in atenolol-treated subjects after six months' treatment. The changes in triglyceride concentration could not be ascribed to variations in plasma insulin, growth hormone, or glucagon concentrations. Basal FFA concentrations were reduced during the first three months of treatment in both groups but returned to pretreatment levels after six months. Plasma cholesterol concentrations were unchanged by either agent.

Adult

Interaction of normal and unusually modified microbial DNA with cultured mammalian cells. Breakdown and reincorporation vs. uptake of polymerized DNA.

The uptake of radioactively labeled bacterial and phage DNA and the incorporation of acid-soluble DNAase I digests of these DNAs by cultures of human foreskin and 3T3 cells were studied. The presence of large amounts of unusually modified pyrimidine residues in donor phage DNAs allowed radioactive donor DNA in the nuclei of DNA-treated cells to be distinguished from host DNA labeled with breakdown products derived from donor DNA. This distinction could be made because it was found that radioactively labeled 5-methylcytosine residues in predigested XP-12 DNA and glucosylated 5-hydroxymethylcytosine residues in predigested T4 DNA could not be incorporated in an unaltered form into animal cell DNA. The results obtained from the study of uptake of these DNAs suggest that approx. 4--40 ng of phage DNA per 10(6) cells was transported to the nuclei of DEAE-dextran-pretreated cells during 3 days of incubation in medium after treatment with the DNA. However, interpretation of the results is complicated by the finding of considerable amounts of donor DNA binding to and persisting at the cell surface, which might attach to nuclei during subcellular fractionation.

Bacteriophages

Pruritus in diabetes mellitus: investigation of prevalence and correlation with diabetes control.

Three hundred diabetic and 100 nondiabetic hospital outpatients (both groups of comparable age and sex distribution) were assessed for the presence of generalized and localized pruritus. Pruritus vulvae was significantly more common in diabetic women (18.4%) than in controls (5.6%) and was significantly associated with poor diabetes control (mean glycosylated hemoglobin level less than 12%). Other forms of localized pruritus were equally common in diabetic and nondiabetic patients, regardless of glycosylated hemoglobin levels. Generalized pruritus was present in 14 diabetic patients, but in 5 cases the symptom was ascribed to intercurrent illness or drug administration. Thus, generalized pruritus without apparent cause was present in only 8 diabetic patients (2.7%) and was not significantly more common than in nondiabetic patients. It is doubtful if diabetes mellitus per se should be regarded as a cause of generalized or localized pruritus, other than pruritus vulvae.

Adolescent