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Biomedical subjects

D Watson

Publications and source records attributed to D Watson.

At least 19 recordsLinked to original sources

The effect of budesonide and triamcinolone acetonide on hepatic microsomal testosterone metabolism in the rat.

The hepatic microsomal metabolism of testosterone was studied in male rats after treatment with either budesonide or triamcinolone acetonide for 13 weeks. The in vitro metabolism was determined using a testosterone concentration of 35 nM which is comparable to the levels found in plasma. It was shown that the total microsomal testosterone metabolism was decreased in budesonide-treated rats and increased in rats treated with triamcinolone acetonide. The testosterone metabolites produced were measured and thus it was revealed that budesonide treatment brought about its effect through a 50% decrease in the activity of steroid 5 alpha-reductase, but did not affect other reductive enzymes, or the oxidation of testosterone. Triamcinolone acetonide treatment decreased steroid 5 alpha-reductase activity by 95% and also decreased the activities of steroid 3 alpha- and 3 beta-reductases by more than 90%. In addition, treatment with triamcinolone acetonide caused a 50% increase in the oxidative metabolism of testosterone, which resulted in the observed increase in total testosterone metabolism. The presence of 0.1 microM budesonide in the microsomal incubations was without effect on testosterone metabolism. However, 0.1 microM triamcinolone acetonide inhibited testosterone oxidation by 65%, without affecting the reductive pathway of testosterone metabolism.

Animals

Effects of type of dietary protein on acid-base status, protein nutritional status, plasma levels of amino acids, and nutrient balance in the very low birth weight infant.

STUDY OBJECTIVE: To determine the effect of the type of dietary protein (3.3 gm/kg per day) on acid-base status, protein nutritional status, plasma amino acid concentrations, and nutrient (nitrogen, fat, mineral, trace element) balance. SUBJECTS: Preterm infants (birth weight less than or equal to 1250 gm, gestational age less than or equal to 32 weeks) with no evidence of systemic disease, who had achieved a minimal enteral intake of 110 kcal/kg per day by 21 days of age. INTERVENTIONS: Each infant was fed three study formulas that differed only with respect to the ratio of whey to casein (60:40, 35:65, 18:82). Each formula was given for 1 week. At the end each week, blood was drawn and a 48-hour balance was determined. MAIN RESULTS: Late metabolic acidosis, uremia, and hyperammonemia were not observed. No differences in pH or serum bicarbonate were noted. Base excess was greater with the casein-predominant formula (18:82 greater than 35:65, 60:40) but remained within normal limits for the preterm infant. Plasma concentrations of threonine (60:40 greater than 35:65 greater than 18:82), phenylalanine, and tyrosine (18:82 greater than 35:65 greater than 60:40) differed. Nitrogen absorption (60:40 less than 35:65, 18:82), nitrogen retention (60:40 less than 35:65, 18:82), fat absorption (60:40, 35:65 greater than 18:82), and phosphorus absorption (60:40 less than 35:65, 18:82) also differed. CONCLUSIONS: At an intake of 3.3 gm/kg per day, the type of dietary protein had little effect on metabolic status. Differences in plasma amino acid concentrations and nutrient balance suggest that a formula containing protein with a whey/casein ratio of 35:65 may be preferable to that with a whey/casein ratio of 60:40 or 18:82 for the very low birth weight infant.

Acid-Base Equilibrium

Affect, personality, and social activity.

These studies examined relations between social activity and state and trait measures of Positive and Negative Affect. In Study 1 Ss completed scales relevant to 3-factor models of personality and a weekly mood and social activity questionnaire for 13 weeks. In Study 2 Ss completed measures of the 5-factor model of personality and a daily mood and social activity survey for 6-7 weeks. In within- and between-Ss analyses, socializing correlated significantly with state measures of Positive Affect and with trait measures of Extraversion/Positive Emotionality. These relations were relatively general across various types of positive affect and social events; however, specific types of social events also were differentially related to affect. In contrast, social activity had no consistent association with measures of Negative Affect or the other personality dimensions. The results support a temperamental view of Extraversion.

Adult

Prior chemotherapy does not prevent effective mobilisation by G-CSF of peripheral blood progenitor cells.

In this study we demonstrate that the hemopoietic growth factor, G-CSF successfully mobilised progenitor cell populations into the peripheral blood in a population of patients despite intensive pretreatment with chemotherapy. Administration of G-CSF increased the numbers of peripheral blood progenitor cells (PBPC) by a median of 76-fold above basal levels. Maximal levels of PBPC were observed on days 5 and 6 after G-CSF treatment. In two patients a second cycle of G-CSF mobilised PBPC to levels comparable with those seen after the first cycle of G-CSF treatment. An earlier hemopoietic cell population (pre-CFC's) was also mobilised with levels increased up to 50-fold above basal levels. Using a standard mononuclear cell leukapheresis technique the PBPC were collected extremely efficiently (essentially 100%) and could be further successfully enriched by separation using a Ficoll gradient. For patients who underwent the optimal collection protocol (i.e. leukapheresis on days 5, 6 and 7) a total of 32 +/- 6 x 10(4) GM-CFC kg-1 were collected. The ability to mobilise PBPC using G-CSF alone and to successfully and efficiently harvest these cells has important implications for the future of transplantation and high dose chemotherapy procedures.

Adolescent

Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine.

The Centers for Disease Control recommends that, because of a greatly increased susceptibility to pneumococcal infection, all persons infected with human immunodeficiency virus (HIV) receive pneumococcal vaccine. Using an ELISA specific for antibody to capsular polysaccharide, a postvaccination antibody was evaluated to five commonly infecting serotypes of Streptococcus pneumoniae. Thirty-nine HIV-infected persons with less than or equal to 500 CD4 cells exhibited significantly fewer responses than did healthy controls; overall, only 46 (24%) of 195 possible responses were positive compared with 45 (75%) of 60 in 12 HIV-infected subjects with greater than 500 CD4 cells and 92 (74%) of 125 in 25 healthy controls (P less than .001). Subjects with less than or equal to 500 CD4 cells responded to a mean of 1.1 antigens versus a mean of 3.8 and 3.7 in those with greater than 500 CD4 cells and controls, respectively (P less than .001). There were no differences between responses in those with less than 200 and those with 200-500 CD4 cells. Within groups stratified by CD4 cell counts, further stratification by clinical status did not reveal significant differences. Since asymptomatic HIV-infected persons with less than 500 CD4 cells show abnormal responses, pneumococcal vaccine should be given when HIV infection is first detected.

Adult

Oxyhaemoglobin saturation following elective abdominal surgery in patients receiving continuous intravenous infusion or intramuscular morphine analgesia.

Oxygen saturation was continuously measured using computerised pulse oximetry for 8 h overnight pre-operatively and for the first 24 h postoperatively in 40 patients receiving intermittent intramuscular morphine or continuous infusion of morphine following elective upper abdominal surgery. The proportion of time with an oxygen saturation less than 94% was used as an index of desaturation. Patients receiving continuous infusion analgesia received a larger morphine dose and achieved better analgesia than the intramuscular group. Postoperatively, the duration of desaturation increased 10-fold over pre-operative values, 'intramuscular' patients spending 39.0% (SD, 37.0%) and 'continuous infusion' patients 40.0% (SD, 37.5%) of the time below 94% saturation. Although newer therapies (e.g. epidural analgesia and patient-controlled analgesia) are currently receiving greater attention, the sequelae of these more traditional analgesic techniques warrant further study.

Abdomen

On traits and temperament: general and specific factors of emotional experience and their relation to the five-factor model.

In this article we investigate relations between general and specific measures of self-rated affect and markers of Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Replicating previous research, we found strong and pervasive associations between Neuroticism, its facets, and the various negative affects; and between Extraversion, its facets, and the positive affects. Conscientiousness also had a significant, independent relation with general positive affect, but this effect was entirely due to the specific affect of attentiveness, which was more strongly related to Conscientiousness than Extraversion. Conversely, only the achievement facet of Conscientiousness correlated broadly with the positive affects. Finally, hostility had a strong independent association with (low) Agreeableness. The results for Neuroticism and Extraversion further clarify the temperamental basis of these higher order trait dimensions; whereas those obtained for Agreeableness and Conscientiousness illustrate the importance of examining personality-affect relations at the lower order level.

Adult

Lung function testing in adults with preferential nasal breathing.

Three adult patients with asthma with preferential nasal breathing were found to have a typical pattern of lung function test results with substantial between test variation. This condition can be identified as a cause of unsatisfactory performance in respiratory tests by observing the patient's reaction after the nostrils have been occluded.

Aged

Release of mucus glycoconjugates by Pseudomonas aeruginosa rhamnolipid into feline trachea in vivo and human bronchus in vitro.

Pseudomonas aeruginosa colonizes the lower respiratory tracts of patients with severe bronchiectasis, including cystic fibrosis, a condition associated with increased airway mucus output. We have shown that an extract containing chloroform-soluble extracellular products of P. aeruginosa releases glycoconjugates into the cat trachea in vivo. This activity was not related to pyocyanin, a major component of the extract, but was associated with the rhamnolipids. Purified monorhamnolipid (100 micrograms/ml) released radiolabeled and periodic acid-Schiff (PAS)-reactive glycoconjugates (delta 3H = +490 +/- 70%, delta 35S = +170 +/- 40%, delta PAS = +8.6 +/- 1.7 micrograms/min; n = 6, P less than 0.02 for each). Dirhamnolipid (200 micrograms/ml) was also effective (delta 3H = +640 +/- 70%, delta 35S = +130 +/- 20%, delta PAS = +9.3 +/- 1.5 micrograms/min; n = 6, P less than 0.02 for each). Monorhamnolipid (100 micrograms/ml) also released 35S-labeled and PAS-reactive glycoconjugates from human bronchial tissue in vitro (delta 35S = +189 +/- 47%, delta PAS = +26.3 +/- 8.5 micrograms/min; n = 7, P less than 0.001 versus control tissues in which no stimulus was given). The cat tracheal glycoconjugates released by the rhamnolipids differed from those released by pilocarpine 50 microM, in having a higher 3H:35S ratio (P less than 0.001). After gel chromatography on a Sepharose CL-4B column, the void volume fractions of the glycoconjugates also had different profiles in a cesium chloride density gradient. Those released by rhamnolipid banded at 1.62 g/ml, while those released by pilocarpine banded mainly at 1.50 g/ml, with some of the higher density material also present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Central conduction time in childhood autism.

To investigate the integrity of the brain-stem in 20 mentally handicapped children who met the Rutter criteria for autism, brain-stem auditory evoked potentials were obtained for a range of stimulus intensities. Central conduction times (CCTs) were calculated for the Wave I-Wave V interval of the brain-stem potentials. In children under 14 years of age CCTs were normal. In children 14 years of age and over, three of four girls and eight of nine boys had CCTs exceeding normal limits when compared with a group of controls of normal intelligence, matched for age and sex. CCTs recorded from a group of non-autistic mentally handicapped children were within normal limits. The age distribution are consistent with a maturational defect in myelination within the brain-stem in autism, a defect which may have a much wider anatomical distribution throughout cortical and subcortical structures.

Adolescent

e-PTFE ventricular shunt catheters.

The perfect polymer surface for implantation should resist the adhesion of bacteria while producing no reaction in surrounding tissues. Silicone elastomer is a common material used for medical implantation devices. This material is superior to most available for implantation because of its flexibility and low, but detectable, tissue reaction. We have evaluated a flexible, expanded polytetrafluoroethylene (e-PTFE) ventricular catheter for cerebrospinal fluid shunting and have found that although e-PTFE is safe for cerebral implantation, the porosity of the material allows tissue ingrowth that obstructs the lumen. Our limited clinical evaluation of 5-microns internodal distance e-PTFE revealed that this open-cell structure, allowing tissue ingrowth, apparently is a poor candidate to replace silicone elastomer in cerebrospinal fluid shunting devices. However, further investigation may provide a polymer superior to silicone elastomer to create a cerebrospinal fluid shunt.

Animals

Specific degenerate codons enhanced selective expression of human parathyroid hormone in Escherichia coli.

Specific degenerate codons in the amino-terminal region of a synthetic human parathyroid hormone (PTH) gene exerted dramatic effects on both products and yield of expression of this 84-amino acid polypeptide in Escherichia coli. With adenine-rich degenerate codons constituting the PTH-(1-5) region, intact PTH has been expressed as the only PTH product at 6.5 mg/liter. In contrast, with guanine-rich degenerate codons, the predominent product was analogue PTH-(8-84). Use of cytosine- or thymine-rich degenerate codons generated only a small amount of immunoreactive product (0.2 mg/l). With the amino terminal region reconstituted with adenine-rich degenerate codons, the mid and carboxyl regions of the synthetic gene were also reconstructed to imitate the E. coli-favored codon degeneracy. Expression yielded the intact PTH at 20 mg/liter. Gel electrophoresis and Western blots, with antibodies specific to the amino or carboxyl terminus of PTH, indicated only a single PTH-related polypeptide, with the same mobility as a synthetic intact PTH sample. Amino acid sequencing, composition analysis, mass spectrometry, and the adenylate cyclase bioassays confirmed the purified product as the processed intact PTH.

Amino Acid Sequence

Analysis of vitamin D and its metabolites using thermospray liquid chromatography/mass spectrometry.

A new method is described for the analysis of vitamin D and its metabolites utilizing thermospray (TSP) mass spectrometry as an on-line detector for high performance liquid chromatography. Ionization conditions were optimized for use with isocratic reversed phase chromatography. TSP mass spectrometry was employed in series with a UV absorbance detector to facilitate comparisons between the two methods of detection. Positive ion TSP mass spectra were recorded for vitamin D2, vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). The spectra contained protonated molecular ions, ammonium adduct ions and fragment ions due to the loss of one or more molecules of water. A comparison of quantitative precision was made by determining UV absorbance and TSP standard curves for vitamin D3 using two different methods: (1) External standard method with post-column (post UV detector) addition of ammonium acetate. (2) As (1) but using the method of internal standards with a closely eluting internal standard (vitamin D2). In each case the quantitative precision (correlation coefficient) for UV absorbance detection was superior owing to intrinsic instability of the TSP ion beam. A stable isotopically labelled internal standard was employed in the development of an assay for 1,25(OH)2D3. The assay was used to quantify in vitro enzymic conversion of 25(OH)D3 to 1,25(OH)2D3 in guinea pig and sheep renal mitochondrial incubations. TSP LC/MS was also applied to analysis of an extract of human blood plasma in which D3 and each of its principal metabolites were identified in a single analysis.

24,25-Dihydroxyvitamin D 3

Regional variation in the abundance of axonal cytoskeletal proteins.

The relative abundance of several axonal cytoskeletal proteins was determined by immunoassay at various sites in the peripheral and central nervous systems of adult rats. Within the peripheral nervous system, the ratio of tubulin to neurofilaments was greatest for nerves composed of unmyelinated axons and least for nerves with large myelinated axons. MAP1 protein was more prominent in unmyelinated fibers; conversely tau proteins were relatively more abundant in large myelinated axons. An immunochemical index of neurofilament phosphorylation was less for unmyelinated fibers than for myelinated ones. In the fimbria-fornix, pyramidal tract, and superior cerebellar peduncle, similar trends were observed: small axons had more MAP1, less tau, and a greater ratio of tubulin to neurofilament proteins. The phosphorylation index was greatest for the superior cerebellar peduncle, the tract with the largest axons. The immunochemical index of neurofilament phosphorylation was greater for the optic nerve than for axonal tracts in the brain proper. These results suggest that development of large myelinated axons is associated with greater neurofilament content, neurofilament phosphorylation, and with greater abundance of tau proteins in the CNS and the PNS; however, quantitative aspects of these relationships differ in the PNS and the CNS.

Animals

Tripartite model of anxiety and depression: psychometric evidence and taxonomic implications.

We review psychometric and other evidence relevant to mixed anxiety-depression. Properties of anxiety and depression measures, including the convergent and discriminant validity of self- and clinical ratings, and interrater reliability, are examined in patient and normal samples. Results suggest that anxiety and depression can be reliably and validly assessed; moreover, although these disorders share a substantial component of general affective distress, they can be differentiated on the basis of factors specific to each syndrome. We also review evidence for these specific factors, examining the influence of context and scale content on ratings, factor analytic studies, and the role of low positive affect in depression. With these data, we argue for a tripartite structure consisting of general distress, physiological hyperarousal (specific anxiety), and anhedonia (specific depression), and we propose a diagnosis of mixed anxiety-depression.

Anxiety Disorders