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Biomedical subjects

K Bowman

Publications and source records attributed to K Bowman.

At least 19 recordsLinked to original sources
PubMed2002

Characterization of nuclease-resistant ribozymes directed against hepatitis B virus RNA.

Hepatitis B virus (HBV) is responsible for > 350 million cases of chronic hepatitis B worldwide and 1.2 million deaths each year. To explore the use of ribozymes as a novel therapy for HBV infection, nuclease-resistant ribozymes that target highly conserved regions of HBV RNA were screened in cell culture. These synthetic ribozymes have the potential to cleave all four major HBV RNA transcripts and to block the HBV lifecycle by cleavage of the pregenomic RNA. A number of the screened ribozymes demonstrate activity in cell culture systems, as measured by decreased levels of HBV surface antigen, HBV e antigen and HBV DNA. In addition, a lead anti-HBV ribozyme maintains activity against a lamivudine-resistant HBV variant in cell culture. Treatment of HBV transgenic mice with lead anti-HBV ribozymes significantly reduced viraemia compared with saline-treated animals and was as effective as treatment with lamivudine. In conclusion, the therapeutic use of a ribozyme alone or in combination with current therapies (lamivudine or interferons) may lead to improved HBV therapy.

Animals↗
PubMed1998

Resistance-modifying agents. 5. Synthesis and biological properties of quinazolinone inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP).

Clinical studies concerning the role of poly(ADP-ribose) polymerase (PARP) in the repair of drug- and radiation-induced DNA damage have been impeded by the poor solubility, lack of potency, and limited specificity of currently available inhibitors. A series of 2-alkyl- and 2-aryl-substituted 8-hydroxy-, 8-methoxy-, and 8-methylquinazolin-4(3H)-ones has been synthesized and evaluated for PARP inhibitory activity in permeabilized L1210 murine leukemia cells. 8-Methoxy- and 8-methylquinazolinones (14-34) were readily prepared by acylation of 3-substituted anthranilamides with the appropriate acid chloride, followed by base-catalyzed cyclization. The requisite 8-hydroxyquinazolinones (6, 35-39) were synthesized by demethylation of the corresponding 8-methoxyquinazolinones with BBr3. N-Methylation of 8-methoxy-2-methylquinazolinone (15) with MeI, followed by O-demethylation by BBr3, afforded the control N3-methylquinazolinones 42 and 43, respectively. In general, an 8-hydroxy or 8-methyl substituent enhanced inhibitory activity in comparison with an 8-methoxy group. 2-Phenylquinazolinones were marginally less potent than the corresponding 2-methylquinazolinones, but the introduction of an electron-withdrawing or electron-donating 4'-substituent on the 2-aryl ring invariably increased potency. This was particularly evident in the 8-methylquinazolinone series (IC50 values 0.13-0.27 microM), which are among the most potent PARP inhibitors reported to date. N3-Methylquinazolinones 42 and 43 were essentially devoid of activity (IC50 values > 100 microM). In studies with L1210 cells in vitro, a concentration of 200 microM 8-hydroxy-2-methylquinazolinone (6, NU1025) (IC50 value 0.40 microM) potentiated the cytotoxicity of the monomethylating agent 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide and gamma-radiation 3.5- and 1.4-fold, respectively, at the 10% survival level.

Alkylating Agents↗
PubMed1998

Bioseparation and bioanalytical techniques in environmental monitoring.

The growing use of antibody-based separation methods has paralleled the expansion of immunochemical detection methods in moving beyond the clinical diagnostic field to applications in environmental monitoring. In recent years high-performance immunoaffinity chromatography, which began as a separation technique in biochemical and clinical research, has been adapted for separating and quantifying environmental pollutants. Bioaffinity offers a selective biological basis for separation that can be incorporated into a modular analytical process for more efficient environmental analysis. The use of immunoaffinity chromatography for separation complements the use of immunoassay for detection. A widely used immunochemical detection method for environmental analyses is enzyme immunoassay. The objective of this paper is to review the status of bioaffinity-based analytical procedures for environmental applications and human exposure assessment studies. Environmental methods based on bioaffinity range from mature immunoassays to emerging techniques such as immunosensors and immunoaffinity chromatography procedures for small molecules.

Biosensing Techniques↗
PubMed1992

Music-dependent memory in immediate and delayed word recall.

Undergraduate volunteers rated a series of words for pleasantness while hearing a particular background music. The subjects in Experiment 1 received, immediately or after a 48-h delay, an unexpected word-recall test in one of the following musical cue contexts: same cue (S), different cue (D), or no cue (N). For immediate recall, context dependency (S-D) was significant but same-cue facilitation (S-N) was not. No cue effects at all were found for delayed recall, and there was a significant interaction between cue and retention interval. A similar interaction was also found in Experiment 3, which was designed to rule out an alternative explanation with respect to distraction. When the different musical selection was changed specifically in either tempo or form (genre), only pieces having an altered tempo produced significantly lower immediate recall compared with the same pieces (Experiment 2). The results support a stimulus generalization view of music-dependent memory.

Affect↗
PubMed1991

Predicting the future position of a moving target.

Three experiments were conducted to examine the processes underlying the prediction of the future position of a moving target. A target moved horizontally across a computer screen at constant velocity, disappearing partway across the screen, and subjects responded when they estimated the target would have passed a point on the far side of the screen, had it continued on its path. The first experiment demonstrated that visual tracking of the target is not necessary for successful position estimation. In the second experiment, the time over which the prediction was made rather than the interval for which the target was visible, the distance over which the prediction was made, or the velocity of the target, was found to affect performance. Finally, performance was not affected when markers were placed parallel to the trajectory of the target; the presence of gratings which masked portions of the target's path did not affect subjects' performance. The previous literature suggests that the spatial interval over which predictions are made is the important variable; we find that temporal factors are the major determinants of prediction.

Acceleration↗
PubMed1991

The influence of caregiving and bereavement support on adjusting to an older relative's death.

This study examines the influence of both caregiving social support to an impaired older relative and bereavement social support to a surviving caregiver on that caregiver's bereavement adjustment. Although past research has considered the link between bereavement support and adjustment to a loved one's death, the influence of support to the care recipient has not been investigated. Analyses of prospective panel data from 73 spouse and adult-child caregivers show caregiving support characteristics to be more important for bereavement adjustment than support provided to the surviving caregiver after their relative's death.

Aged↗
PubMed1990

Workstation variables and visual discomfort associated with VDTs.

We have investigated the effects of a range of workstation factors upon the visual symptoms experienced by a group of 92 visual display terminal (VDT) users. Subjects in the study kept a diary over five consecutive working days in which they recorded the types of visual and postural symptoms which occurred and the types of work tasks being performed. Each subject's workstation was analysed for screen legibility and stability, discomfort and disability glare, and required head postures. By the use of multiple regression analysis techniques we have considered the relative contribution of these factors to the symptoms reported by the users of these workstations. Screen legibility significantly influenced the occurrence of symptoms of ocular discomfort and vertical head movements significantly affected the incidence of postural/headache symptoms.

Journal Article↗
PubMed1990

The transition from caregiving to bereavement: the relationship of care-related strain and adjustment to death.

This study examines two competing hypotheses about the relationship between care-related strain and the difficulty adjusting to the impaired relative's death. One hypothesis, and the limited available empirical evidence, suggests that family members who perceive caregiving as stressful will experience some relief when their relative dies because care responsibilities end. An alternative hypothesis, derived from several conceptualizations, posits the opposite relationship, with greater care-related strain predictive of greater strain during bereavement. Panel data from spouse and adult-child caregivers collected before and after the death support the second hypothesis. Respondents who appraise caregiving as more difficult and those who report more negative caregiving consequences for the family assess bereavement as more difficult and report greater bereavement strain for the family.

Aged↗
PubMed1989

The effect of norepinephrine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

alpha-Adrenergic drugs improve cerebral blood flow (CBF) during cardiopulmonary resuscitation (CPR), in part, by reversing carotid artery collapse and by shunting blood from extracerebral to intracerebral vascular structures. Adrenergic drugs with beta 2-agonist properties may cause peripheral vasodilation, and thus may be less beneficial in this setting. The purpose of this study was to compare epinephrine (E), an alpha 1,2, beta 1,2-agonist, with norepinephrine (NE), an alpha 1,2, beta 1-agonist, on CBF during CPR. Twenty swine each weighing greater than 15 kg were instrumented for regional CBF measurements using tracer microspheres. Regional CBF was measured during normal sinus rhythm (NSR). Animals were then placed into ventricular fibrillation (VF). After ten minutes of VF, the animals received closed-chest CPR using a mechanical thumper. Regional CBF was measured during CPR. After three minutes of CPR, the animals were allocated to receive either E, 0.20 mg/kg (N = 5); NE, 0.08 mg/kg (N = 5); NE, 0.12 mg/kg (N = 5); or NE, 0.16 mg/kg (N = 5). Regional blood flows were again measured following drug administration. CBFs following drug administration were compared using an analysis of covariance adjusting for baseline differences during CPR. A Newman-Keuls multiple comparison was used to follow-up significant (P less than or equal to .05) differences. Statistical significance was considered at P less than or equal to .05. There was a clinically significant improvement in cerebral cortical flow with NE, 0.12 mg/kg, and NE, 0.16 mg/kg, compared with NE, 0.08 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Age-related changes in contrast sensitivity in central and peripheral retina.

Eight young (average age 20.4 years) and eight elderly (average age 64.4 years) observers took part in three experiments designed to study age-related changes in peripheral retinal function. A further eight young (average age 22.3 years) and eight elderly (average age 63.8 years) observers took part in a replication of experiment 3. All observers had normal or better-than-normal visual acuity and no evidence of ocular pathology. All testing was monocular and the eye with better visual acuity was used. In the first experiment contrast sensitivity was measured in central retina and 10 deg temporally, at spatial frequencies of 0.2, 0.8, 2.0, and 5.0 cycles deg-1. Young observers had better contrast sensitivities than older observers, but only at higher spatial frequencies (2.0 and 5.0 cycles deg-1). For both groups, contrast sensitivity was poorer with peripheral presentation of stimuli than with central presentation, but not for the lowest spatial frequency used (0.2 cycle deg-1). In the second experiment observers had to detect the presence of a sharp edge (square-wave luminance profile), while in the third and fourth experiments the target was a "fuzzy' edge (sine-wave profile). Edges were again presented centrally or 10 deg temporally. As expected from the data of experiment 1, young observers were better able to detect the sharp edge than were the older observers in both central and peripheral viewing conditions. For both age groups, edge detection was better during central viewing than during peripheral viewing. However, contrary to expectations based on the results of experiment 1, detection of the fuzzy edge was better for central than for peripheral viewing for both age groups in experiments 3 and 4. The apparent (and expected) equality of performance found in experiment 3 for young and elderly observers in detecting the fuzzy edge was shown to be due to the range of contrast values used. When appropriate contrast values were used in experiment 4, young observers detected fuzzy edges presented in central retina better than did elderly observers. The results of experiment 1 show sparing of the ability to process low spatial frequencies across (i) age and (ii) retinal location, and are discussed in terms of the notion of (i) models of age-related loss of visual function and (ii) cortical magnification. The results of experiments 2, 3, and 4 provide some support for the proposition that the contrast sensitivity of observers may be used to predict their performance on other visual tasks.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1986

Mobile arm supports: criteria for successful use in muscle disease patients.

Twenty-nine subjects who had been fitted with mobile arm supports 6 months to 11 years prior to the initiation of this study were evaluated to determine criteria for successful use of such supports. All subjects were diagnosed as having Duchenne muscular dystrophy or spinal muscular atrophy. Three methods were used to collect data: 1) review of medical charts, 2) interview with patient and family member(s), and 3) observation of the patient in his wheelchair for sitting stability, adjustment and control of the mobile arm support, and speed and efficiency in self-feeding with and without the support. The physical criteria previously established for optimal use were met by the successful users in the sample except for presence of elbow flexion contractures. Among those who had curvature of the spine, spinal fusion increased the percentage of successful users of mobile arm supports. Successful use declined with muscle grades of below poor in elbow flexors. The incidence of success was greater when the tasks of self-feeding, driving a motorized wheelchair and performing leisure skills could be accomplished only with the support. Primary reasons for early rejection of the support were related to attitude toward the equipment, influence of the social support system, and patterns of activities performed with the equipment.

Activities of Daily Living↗
PubMed1984

Possible prediction of accelerated osteoporosis by alkaline phosphatase isoenzymes.

We observed that patients with a variety of metabolic bone diseases had elevated fractions of bone alkaline phosphatase as determined by polyacrylamide disc electrophoresis and thermostability studies. We undertook an epidemiologic investigation to determine if there is any causal relationship between increased bone alkaline phosphatase in the perimenopausal healthy woman and later development of osteoporosis as reflected in bone fractures. The results after an 8-year follow-up show that the fracture rate in the normal group was statistically significantly lower than the fracture rate in the elevated group after adjustment for chronologic and postmenopausal ages (p = 0.05).

Alkaline Phosphatase↗