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Biomedical subjects

M A Bell

Publications and source records attributed to M A Bell.

At least 19 recordsLinked to original sources

Causes and consequences of recent freshwater invasions by saltwater animals.

Transitions from marine to freshwater habitats constitute dramatic shifts between 'adaptive zones' that have initiated the radiation and speciation of many taxa. As recently as 10?000 years ago, deglaciation resulted in marine fauna being trapped in freshwater lakes. In modern times, human activity has caused the acceleration of freshwater invasions from marine or brackish habitats, leading to serious environmental problems. The rapid pace of these invasions provides ideal opportunities for examining initial responses to environmental change and mechanisms involved in habitat transitions. Despite conservation implications and evolutionary applications, recent transitions to fresh water remain inadequately explored.

Journal Article↗

Language proficiency and the prediction of spontaneous rehearsal in children who are deaf.

This study was an investigation of the role of language proficiency and automatization of language skills in the use of spontaneous rehearsal strategies by children who are deaf. Thirty-one profoundly deaf children, 7 to 13 years old, were given a serial recall task, a test of language proficiency (the Language Proficiency Profile-I), and a rapid automatized naming (RAN) task. Similar to previous studies, when the data were examined by age, an apparent developmental lag was observed in the children's spontaneous use of a cumulative rehearsal strategy. Logistic regression analyses further demonstrated that age was actually a nonsignificant predictor of rehearsal use, but that both language proficiency and the automatization of language skills were highly significant predictors. In subsequent hierarchical analyses, automatized language was a partial mediator of the language proficiency --> rehearsal use relation. These results provided support for the view that automatization of language skills is an important and perhaps necessary contribution to the relation between language proficiency and rehearsal use, but that other additional aspects of language proficiency also affect the child's use of a strategy. These findings were discussed in relation to Cummins' (1984) model of language proficiency.

Adolescent↗

Hospital uses team approach to improve processes, reduce costs.

This article describes a group process and how it was used to reduce reprocessing turnover time and increase the availability of sterilized instruments. A team of staff members used the "Seven Steps to Quality" and an event-related sterility maintenance program, thereby improving patient care and reducing costs. With a defined process, the team members' expertise, and clearly defined objectives and goals, the team was able to complete its work and implement a substantial change in a short amount of time.

Group Processes↗

Preparation and characterization of a cocrystalline suspension of [LysB28,ProB29]-human insulin analogue.

Soluble preparations of [LysB28,ProB29]-human insulin analogue (LysPro) exhibit more rapid absorption than human insulin upon subcutaneous injection. Biphasic mixtures of LysPro and intermediate-acting insulin suspensions could provide advantages over current preparations for the treatment of diabetes. To prepare biphasic mixtures of LysPro, a suspension formulation of the analogue is required. We have devised a method for crystallizing LysPro with the basic peptide protamine yielding neutral protamine LysPro (NPL) suspension. The crystallization conditions are strongly dependent on the precipitation procedure and temperature. Using various techniques, the crystalline and suspension characteristics of NPL are found to be similar to human insulin (neutral protamine Hagedorn, NPH) (8:1 molar ratio insulin:protamine, rod-shaped crystals, particle size of 4.0-6.0 microns, and Point of Zero Charge at 6.0-7.0). Using a dog model with NPL or NPH injected subcutaneously and glucose levels clamped at basal, NPL was found to have kinetic and dynamic responses analogous to human insulin NPH [Cmax (maximal insulin or LysPro concentration, ng/mL) of 2.61 +/- 0.22, NPL; 2.58 +/- 0.36, NPH, attained at Tmax (min) of 93 +/- 22, NPL; 145 +/- 33 NPH, and Rmax (maximal rate of glucose infusion, mg/kg min) of 10.8 +/- 1.2, NPL; 13.2 +/- 1.9, NPH, attained at TRmax (min) of 277 +/- 58, NPL; 265 +/- 38, NPH]. There are no statistically significant differences between the insulin curves or the glucose responses. These results provide insight into the mechanism of action of NPH suspensions and the relationship to duration of action. Furthermore, the formulation of a suspension of LysPro having an intermediate time-action makes possible the preparation of stable biphasic mixtures containing LysPro and NPL.

Analysis of Variance↗

Physical stress testing of insulin suspensions and solutions.

Insulin pen-cartridge devices have evolved in order to increase patient compliance and convenience of use in a portable, multiple dosage device. With the advent of a portable insulin containing device, stability considerations have evolved from standard chemical indicators to include the effects of temperature and agitation on physical characteristics. To address these issues, two automated physical stress tests were developed based on market research data and input from regulatory authorities to understand the effect of thermomechanical stress on the product. First, the temperature cycling and resuspension test (TCRT) includes temperature cycling (25-37 degreesC) combined with agitation. The high temperature and extreme agitation test (HTEAT) includes continuous high temperature (37 degreesC) exposure combined with 4 h daily agitation. The total stress exposure is a function of the temperature, agitation, and time. The tests range from moderate stress (TCRT) to considerable stress (HTEAT) determined from the number of cartridge inversions and average daily temperature. Physical stress testing of both insulin suspensions and solution formulations in cartridges were performed and interpreted with respect to multiple endpoints. For suspensions, prolonged exposure to extreme stress caused the protein to form agglomerates, either in the suspension or adhered to the cartridge walls. In contrast, protein solutions subjected to the same extreme stress conditions did not exhibit any visually detectable change. Visual changes in the product under physical stress conditions can increase dose-potency result variability as well as exhibit acid-insoluble aggregates.

Drug Stability↗

Measuring community mobilization in the Seattle Minority Youth Health Project.

This article assesses the validity and reliability of the approach used to measure community mobilization in the Seattle Minority Youth Health Project (MY Health), a neighborhood-based program to prevent drug use, violence, teen pregnancy, and sexually transmitted diseases (STDs). Two constructs were measured: neighborhood cooperation in solving problems, and sense of pride and identification with the neighborhood. The convergent validity of the measurement approach was assessed by comparing several independent measures of community mobilization generated from surveys of key neighborhood leaders, youth, and parents. For the neighborhood cooperation construct, correlations were uniformly positive across measures from different surveys and statistically significant about a quarter of the time. The correlations for the neighborhood pride construct were weaker and generally not statistically significant. Interrater reliability was low for all of the surveys, possibly reflecting varying ideas about what community mobilization meant among survey respondents.

Adolescent↗

Youth counseled for HIV testing at school- and hospital-based clinics.

The prevalence of human immunodeficiency virus (HIV) in adolescents is difficult to assess as few adolescents consent to testing. This prospective study characterized urban youth requesting HIV testing at two types of health settings, inner-city school-based and hospital-based clinics. Data were obtained on 1652 inner-city youths aged 13 to 19 years who consented to individualized HIV counseling and testing from January 1993 to January 1994. Identified risks for HIV included sexual activity, sexually transmitted disease (STD) history, and substance use by self-report during a confidential structured interview. Data were analyzed using chi-squared analysis. Of the 1652 youth who were counseled, 1602 were from hospital-based clinics. A total of 827 (50%) requested HIV testing. Females accounted for the majority of youth who underwent counseling (79%) and requested HIV testing (75%). However, once counseled, males were more likely to be tested. Risk factors differed by gender; females were more likely to report STDs and marijuana use, and males more likely to report alcohol and cocaine use. These results indicate a need to identify developmentally appropriate methods to educate and counsel youth about HIV that will lead to more youth willing to be tested. School-based clinics may provide easier access than traditional health models for confidential HIV services.

AIDS Serodiagnosis↗

Stroop color-word interference and electroencephalogram activation: evidence for age-related decline of the anterior attention system.

Groups of healthy, community-dwelling younger and older adults performed a Stroop task in which color and word could be congruent or incongruent and spatially integrated or separated. During the task, continuous electroencephalogram (EEG) was recorded from frontal, parietal, and occipital regions. The magnitude of the Stroop interference effect and task-related EEG activation was greater for older than younger adults when stimuli were integrated. This effect was significant over medial and lateral frontal and parietal, but not occipital, regions. In comparison, interference and EEG activation did not differ for younger and older adults when stimuli were separated. These findings support the hypothesis that the anterior attention system is more sensitive to the effects of increasing age than the posterior attention system.

Adolescent↗

Individual differences in object permanence performance at 8 months: locomotor experience and brain electrical activity.

This work was designed to investigate individual differences in hands-and-knees crawling and frontal brain electrical activity with respect to object permanence performance in 76 eight-month-old infants. Four groups of infants (one prelocomotor and 3 with varying lengths of hands-and-knees crawling experience) were tested on an object permanence scale in a research design similar to that used by Kermoian and Campos (1988). In addition, baseline EEG was recorded and used as an indicator of brain development, as in the Bell and Fox (1992) longitudinal study. Individual differences in frontal and occipital EEG power and in locomotor experience were associated with performance on the object permanence task. Infants successful at A-not-B exhibited greater frontal EEG power and greater occipital EEG power than unsuccessful infants. In contrast to Kermoian and Campos (1988), who noted that long-term crawling experience was associated with higher performance on an object permanence scale, infants in this study with any amount of hands and knees crawling experience performed at a higher level on the object permanence scale than prelocomotor infants. There was no interaction among brain electrical activity, locomotor experience, and object permanence performance. These data highlight the value of electrophysiological research and the need for a brain-behavior model of object permanence performance that incorporates both electrophysiological and behavioral factors.

Analysis of Variance↗

Crawling experience is related to changes in cortical organization during infancy: evidence from EEG coherence.

Greenough's model of experience-expectant plasticity was used to examine EEG coherence among four groups of 8-month-old infants that varied in hands-and-knees crawling experience. Groups included prelocomotor infants, novice crawlers with 1-4 weeks experience, infants with 5-8 weeks, and long-term crawlers with 9+ weeks experience. Resting EEG was recorded from frontal, parietal, and occipital sites of both hemispheres. EEG coherence between intrahemispheric sites was computed. Novice crawlers (1-4 weeks) displayed greater coherence than either prelocomotor infants or experienced crawlers. These data suggest that the anticipation and onset of locomotion was related to an overproduction of cortico-cortical connections. Pruning of these overabundant connections may be a source of the decrease in coherence as crawling becomes more routine.

Electroencephalography↗

Relationship of flavonoid oxidation potential and effect on rat hepatic microsomal metabolism of benzene and phenol.

The effect of several flavonoids on the benzene hydroxylase and phenol hydroxylase activity of rat hepatic microsomes was determined. The electrochemical characteristics of the flavonoids were also determined. The effect of flavonoids on microsomal phenol hydroxylase activity was found to correlate well with the oxidation potential for flavonoid aglycones. Easily oxidized flavonoids inhibited phenol hydroxylase activity with the extent of inhibition correlated to the ease of oxidation. This inhibition exhibited dose-dependent behaviour, with concentrations below 1 microM having no effect. On the other hand, flavonoids with high oxidation potentials increased phenol hydroxylase activity in a dose-independent manner. Hydroxyl substitution at C-7 was required for inhibition of phenol hydroxylase activity independently of the oxidation potential. Glycosylation at either C-7 or C-3 was found to moderate the inhibition of phenol hydroxylase activity. A linear relation was found between the degree of inhibition and the number of sugar residues for glycosylated flavonoids. There was no correlation between electrochemical properties and effect on microsomal benzene hydroxylase activity.

Animals↗

Arteriolar tortuosity of the white matter in aging and hypertension. A microradiographic study.

Previous studies have shown tortuous arteries and arterioles in the brains of older people, but the effects of age and other factors have not been studied. To examine the effects of hypertension, age, race and sex on white matter (WM) arteriolar tortuosity (AT), we performed high-resolution microradiography and morphometry of human brains taken at autopsy from 44 subjects of various ages (range 30-96 years; 31 hypertensives/13 normotensives). About 70% of tortuosities in the WM were found at the gray-white interfaces of the insular region and adjacent subcortical-WM of the inferior frontal and superior temporal gyri. Six morphologic types of tortuous profiles were identified. The number of tortuous profiles increased with age, but not significantly. Hypertension, sex and race had no effect on tortuosity. Our findings also suggest that 1) WM AT is found mostly at the interfaces between gray matter and WM and, therefore, 2) the physical properties of the WM somehow predispose to the development of AT; 3) AT is not associated with tortuosity in the veins; and 4) the location of complex arteriolar coils supports a recent claim that they can be mistaken for the Charcôt-Bouchard microaneurysms if injection of contrast media and low-magnification radiography of the brain slices are employed for that purpose.

Adult↗

Microvascular density of the human paraventricular nucleus decreases with aging but not hypertension.

Microvascular density was determined in the supraoptic nuclei (SON) and paraventricular nuclei (PVN) of fixed brain tissue from 19 human subjects ranging in age from 30 to 85 years. Eight of these patients had hypertension. No sex- or hypertension-related differences in microvascular density were found in either the SON or PVN. However, capillary density decreased in the PVN with aging. These results indicate a differential pattern of microvascular loss in the human hypothalamus with aging.

Adult↗

A pilot scheme for improving the accuracy of serum cholesterol measurement in Scotland and Northern Ireland.

The measurement of plasma cholesterol is subject to particularly stringent requirements of bias and imprecision because clinically important action limits lie within the bulk of the population distribution. A pilot scheme was conducted with the aim of improving the accuracy of the assay of cholesterol in 26 laboratories in Scotland and Northern Ireland. This involved the distribution of three sets of authentic human sera with varying cholesterol concentrations assigned by the reference Abell-Kendall method which was established and validated in a central laboratory. The precision (coefficient of variation) of cholesterol testing was 1.71% across all laboratories at the first distribution and this did not alter subsequently. Mean bias was initially 4.07% (median 4.14%) relative to the Abell-Kendall assigned values and this figure had fallen to 1.12% (median 0.92%) by the third distribution. We conclude that through a standardization scheme it is possible in a relatively short time to improve bias significantly and meet the criterion of < 2-3% bias required for optimum cholesterol measurement.

Bias↗

Regulation of the phosphorylation of histones and glycogen synthase.

The phosphorylation of histones and glycogen synthase by protein kinases was analysed by SDS-polyacrylamide gel electrophoresis and autoradiography. The phosphorylation of histone III-S by the catalytic subunit of cyclic AMP-dependent protein kinase (A-PK) or cGMP-dependent protein kinase (G-PK) was inhibited by archidonic acid, sphingosine and staurosporine. Using the catalytic subunit of A-PK, the phosphorylation of histone VIII-S was inhibited by Ca2+, arachidonic acid and staurosporine; the phosphorylation of histone II-S was inhibited by phosphatidyl ethanolamine, phosphatidyl inositol, arachidonic acid and staurosporine; and the phosphorylation of glycogen synthase was inhibited by arachidonic acid and staurosporine. After being phosphorylated by the catalytic subunit of A-PK, calpain II with 4 microM Ca2+ was less effective in degrading histone III-S, which had been prephosphorylated by PK-C.

AMP-Activated Protein Kinases↗

The Charcôt-Bouchard aneurysm controversy: impact of a new histologic technique.

For over a century a controversy has existed about the prevalence and significance of Charcôt-Bouchard (C-B) aneurysms, especially regarding their relationship to intracerebral hemorrhage (ICH) in man. We reassessed C-B aneurysms by staining thick brain sections from 35 hypertensives and 20 normotensives with the alkaline phosphatase (AP) endothelial stain followed by light microscopy and high-resolution microradiography. Charcôt-Bouchard aneurysms were conspicuously absent in both groups which included four cases of hypertensive ICH. The three-dimensional perspective and enhanced ability to trace vessels with these techniques helped to identify arteriolar coils and twists that can be mistaken for aneurysms when demonstrated by injection methods. Routine brain pathologic sections from 2,800 autopsies over a decade showed rare examples of parenchymal aneurysms. We conclude that elimination in our study of a) injection artifacts and b) misinterpretations shows that C-B aneurysms are uncommon and have little relationship to ICH. Despite this, and in view of the original contribution of Charcôt and Bouchard, the occasional examples of brain parenchymal aneurysms should continue to bear their names.

Aged↗