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Biomedical subjects

D A Johnson

Publications and source records attributed to D A Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Virtual reality: a new prosthesis for brain injury rehabilitation.

Virtual Reality (VR) technology is a relatively new application to rehabilitation medicine, yet it offers considerable potential to achieve significant successes in assessment, treatment and improved outcome, thereby increasing our knowledge of neuroplasticity. The capabilities of VR are especially evident in neurological rehabilitation, where cognitive and behavioural problems often interact with physical impairments to reduce the overall level of functioning and interaction. The need for effective interventions in neurological rehabilitation demands communication and collaboration between disciplines. This paper presents some of the current areas of the clinical applications of VR, emphasising the link between experimental evidence on recovery after brain damage and the clinical problems encountered in a ward setting.

Brain Injuries↗
PubMed1998

Virtual environments in brain damage rehabilitation: a rationale from basic neuroscience.

The potential of virtual environments in assessment and training of cognitive function is a more than adequate reason for their application to neurorehabilitation. However, there is a more fundamental justification, and one which is firmly rooted in the neuroscience literature. Over the last half century there has been a wealth of published evidence that enriching the environments of laboratory rats stimulates neuroplastic change in the cerebral cortex, enhances learning and problem solving in normal rats and reduces cognitive impairment in brain damaged rats. Central to all three effects of enrichment are the increased levels of interaction with the physical environment engendered by enrichment. Placing humans who have damaged brains in virtual environments is one way of enhancing their levels of environmental interaction which, because of cognitive impairments and sensory and motor disabilities, is otherwise difficult to achieve. In this chapter we explore the potential of virtual environments as enriched environments within the rehabilitation regime. The underlying assumption, that interaction with a virtual environment is functionally equivalent to interaction with a real environment, is examined. Three lines of relevant evidence are reviewed, neuroimaging studies and psychophysiological studies of people in virtual environments and studies of transfer of training from virtual to real tasks. An agenda for future research in this are is proposed.

Animals↗
PubMed1998

Recombinant human mast cell tryptase beta: stable expression in Pichia pastoris and purification of fully active enzyme.

Human mast cell tryptase beta (EC 3.4.21.59) is a trypsin-like serine protease that is stored in and released from mast cell granules. This enzyme has been expressed in Pichia pastoris via homologous recombination of the cDNA coding for the mature active tryptase with the addition of a KEX 2 processing site into the Pichia genome. Cells producing recombinant human tryptase (rHT) were selected by screening with antibodies. Induction with methanol resulted in the secretion of rHT into the Pichia growth medium; tryptase activity was stabilized by the addition of heparin to the culture medium. Increasing levels of enzyme were detected in the medium for up to 3 days. Fully active enzyme was purified from the culture medium with a 100% yield of activity via a simple two-step procedure, with hydrophobic interaction chromatography followed by affinity chromatography on immobilized heparin. Bands of 33 (faint), 34.2, 35.9 and 50 kDa (diffuse) were observed on SDS/PAGE. These multiple forms were due to differences in post-translational glycosylation of asparagine residues, because enzymic deglycosylation resulted in only one band at 33 kDa. A single symmetrical peak with an estimated size of 197 kDa was obtained on gel filtration. Kinetic analyses in comparison with native human lung mast cell tryptase (HLT) yielded similar Km values, but the kcat of rHT was more than twice that of HLT.

Chromatography, Gel↗
PubMed1998

The 5S rRNA gene in sea barley (Hordeum marinum Hudson sensu lato): sequence variation among repeat units and relationship to the X haplome in barley (Hordeum).

We have investigated the molecular diversity of the 5S rDNA units in sea barley, comprising Hordeum marinum and Hordeum geniculatum. Although we were unable to detect "short" units after screening of 639 clones, we found two unit classes, one 602-607 bp long and the other 507-512 bp long. We classify the shortest unit class of the two as belonging to the "long H1" unit class, identified in previous papers. The longest unit class is not similar to any unit class so far identified, and is therefore unique. It was coined by us as the "long X1," to reflect the X haplome. We present a summary of all the unit classes so far described in Hordeum. We carried out a cladistic analysis, based on the "long H1" (orthologous) sequences, that included H. vulgare, H. spontaneum, H. bulbosum, H. marinum, H. geniculatum, and H. bogdanii. As a result, the first three grouped in one clade, and the other three in the other clade, with the latter clade being more isolated. These results reflect current knowledge of relationships based on morphology, cytology, and genome analysis. Furthermore, the sequences from the 5S unit classes may be potentially useful as DNA probes for genomic identification and genetic transfer in the Triticeae.

Base Sequence↗
PubMed1997

Enhanced plasma DHEAS, brain acetylcholine and memory mediated by steroid sulfatase inhibition.

Steroid sulfatase inhibitors can alter the metabolism of neurosteroids which modulate brain function. Administration of the non-steroidal steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14) to rats for 15 days increased plasma dehydroepiandrosterone sulfate (DHEAS) concentrations by 88.2%, decreased plasma dehydroepiandrosterone (DHEA) concentrations by 84.6%, increased hippocampal acetylcholine (ACh) release determined via in vivo microdialysis by almost 3-fold, and produced a significant blockade of scopolamine-induced amnesia as measured by a passive avoidance test. These results suggest DHEAS rather than DHEA enhances brain cholinergic function and that steroid sulfatase inhibition may become an important tool for enhancing neuronal functions, such as memory, mediated by excitatory neurosteroids.

Acetylcholine↗
PubMed1997

Size matters: the relationship between MMP-9 expression and aortic diameter.

BACKGROUND: Despite a wealth of data detailing increased metalloproteinase (MMP)-9 expression and activity in abdominal aortic aneurysms (AAAs), no studies examine the relationship between aortic size and MMP-9 expression. Because elastolysis occurs early in AAA formation, we hypothesized that MMP-9 expression would vary with aortic diameter. The purpose of this study was to measure MMP-9 mRNA levels in AAAs of various diameters and define the relationship between AAA size and MMP-9 expression. METHODS AND RESULTS: MMP-9 mRNA levels were measured by competitive polymerase chain reaction (PCR) using gene-specific external standards with cDNA from AAAs (n= 19) and normal aortas (n=4). Levels were normalized to GAPDH mRNA, determined separately via competitive PCR, to control for efficiency of reverse transcription. AAA size was measured on CT scans obtained within 6 weeks of surgery. MMP-9/GAPDH mRNA transcript levels in AAAs were expressed as mean+/-SEM and analyzed by ANOVA with a Tukey adjustment. There was a fourfold elevation in MMP-9/GAPDH mRNA transcript levels in 5.0- to 6.9-cm AAAs (98.06+/-15.19) compared with small (3.0- to 4.9-cm) AAAs (20.87+/-5.15, P<.03), large (>7-cm) AAAs (27.16+/-14.56, P<.01), or normal aortas (3.57+/-1.13, P<.003). The results did not change when they were normalized to patient height, nor were there significant differences in risk factors, age, or sex in each AAA group. CONCLUSIONS: MMP-9 mRNA expression is significantly higher in moderate-diameter (5- to 6.9-cm) AAAs than either small (<4.0-cm) or large (>7.0-cm) AAAs. Increased MMP-9 expression may account for the propensity of AAAs >5 cm to continue to expand, in contrast to smaller aneurysms. Lower levels in AAAs >7 cm suggest that increases in other enzymes or in diameter-dependent mechanical stress on the aortic wall are responsible for their characteristic rapid expansion and high rupture rates.

Aged↗
PubMed1997

Effects of estrogen on potassium-stimulated acetylcholine release in the hippocampus and overlying cortex of adult rats.

In vivo microdialysis techniques were used to examine the effects of estrogen on potassium-stimulated acetylcholine release in the hippocampus and overlying cortex of adult, ovariectomized rats. Estrogen treatment resulted in a significant increase in the percent change in acetylcholine release induced by potassium relative to controls, particularly after prolonged (90 min) exposure to high potassium. The data suggest that estrogen may help to maintain cholinergic function under conditions where cholinergic afferents to the hippocampal formation and cortex are challenged or impaired.

Acetylcholine↗
PubMed1997

A population-based study of salivary lysozyme concentrations and candidal counts.

The relationship between salivary lysozyme concentration and oral candida load was examined in 595 adults. Unstimulated whole saliva, and citrate-stimulated parotid and submandibular/sublingual saliva were collected from each participant. Candida colony-forming units (c.f.u.) in unstimulated whole saliva were determined. An enzyme-linked immunosorbent assay for lysozyme using commercially available antibodies was developed. This assay showed a linear relation of salivary lysozyme concentrations from 0.5 to 4.0 ng/ml. Significant negative relations were observed between lysozyme concentration and flow rate: r = -0.16 (p < 0.001) for stimulated parotid and r = -0.22 (p < 0.0001) for stimulated submandibular/sublingual saliva. The lysozyme concentration in stimulated submandibular/sublingual saliva was higher in males than in female, but no sex difference was observed for stimulated parotid saliva. The lysozyme concentration of stimulated parotid saliva was positively correlated with candida counts (r = 0.18: p < 0.005). Further study of groups according to their levels of candida in whole saliva revealed that lysozyme concentrations were higher in the high candida (> or = 1000 c.f.u./ml) group than in the zero and moderate candida categories in stimulated parotid saliva (p < 0.001): there were no concentration differences in stimulated submandibular/sublingual saliva. These results suggest that parotid lysozyme concentration increases as candida load increases.

Adult↗
PubMed1997

Memory enhancement mediated by the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine.

The intent of this study was to determine whether altering the metabolism of neurosteroids via blockade of the enzyme, steroid sulfatase, could enhance memory retention in rats. The steroid sulfatase inhibitor p-O-(sulfamoyl)-N-tetradecanoyl tyramine (DU-14) was administered alone and in combination with the neurosteroid dehydroepiandrosterone sulfate (DHEAS) to rats which were then tested for the reversal of scopolamine-induced amnesia. A single 30 mg/kg IP dose of DU-14 produced a significant inhibition of steroid sulfatase activity in both brain (14.8%), and liver (85.2%) tissues, 24 hours following administration. In a passive avoidance test, DU-14 enhanced the reversal of amnesia by DHEAS. These results suggest that steroid sulfatase inhibition can potentiate the memory enhancing properties of DHEAS.

Adjuvants, Anesthesia↗
PubMed1997

Chronic steroid sulfatase inhibition by (p-O-sulfamoyl)-N-tetradecanoyl tyramine increases dehydroepiandrosterone sulfate in whole brain.

Dehydroepiandrosterone sulfate (DHEAS) is a neurosteroid which functions as a negative allosteric modulator of the GABA(A) receptor-gated chloride channel. Steroid sulfatase inhibitors including (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14), can potentiate the blockade of the amnestic effects of scopolamine by exogenously administered DHEAS. Moreover, when administered over a 15 day period, DU-14 can block scopolamine amnesia without the concurrent administration of DHEAS. Since the enzyme, steroid sulfatase, facilitates the hydrolysis of the sulfate moiety from DHEAS, the intent of this study was to determine whether chronic administration of DU-14 could increase whole brain concentrations of endogenous DHEAS. Rats were administered DU-14 or corn oil vehicle for 15 days. Following the last day the animals were sacrificed and the brains were removed and analyzed for DHEAS content. DU-14 increased the whole brain concentration of DHEAS 77.6%, from 0.65 +/- 0.06 to 1.15 +/- 0.12 microg/g (mean +/- SEM). This result suggests that steroid sulfatase inhibitors may enhance cognitive function following chronic treatment by increasing the concentration of excitatory neurosteroids such as DHEAS in the brain. Steroid sulfatase inhibitors, therefore, may provide a novel mechanism for facilitating central nervous system function.

Animals↗
PubMed1997

Structure-activity relationship studies of the amide functionality in (p-O-sulfamoyl)-N-alkanoyl tyramines as estrone sulfatase inhibitors.

Recently, we reported the synthesis and biomedical studies of a series of (p-O-sulfamoyl)-N-alkanoyl tyramines as nonsteroidal estrone sulfatase inhibitors. One of the most potent inhibitors in this series is (p-O-sulfamoyl)-N-tridecanoyl tyramine 1 with an 1C50 value of 61.3 nM. In this study, we synthesized four analogs of 1 (compounds 2-5) to investigate the structure-activity relationships of the amide functionality in (p-O-sulfamoyl)-N-tridecanoyl tyramine. Replacement of the amide functionality in 1 with an ethylene moiety to form the alkyl analog 5 resulted in complete loss of sulfatase inhibitory activity (IC50 of 61.3 nM vs. > 20 microM). The keto, hydroxy, and ester analogs (inhibitors 2-4) are 8-15 times less in affinity to the sulfatase than inhibitor 1. However, their inhibitory activities are significantly higher than the alkyl analog 5. The results suggest that the amide functionality is favorable for sulfatase inhibitory activity and that there may be a hydrogen bonding component to the enzyme interaction in this region.

Amides↗
PubMed1997

Ocular and orbital trauma from water balloon slingshots. A clinical, epidemiologic, and experimental study.

PURPOSE: The authors report the findings of 17 patients with ophthalmic injuries produced by launched water balloons; they determine water balloon kinetic energies in experimental and theoretical studies. METHODS: Six case summaries are presented; one case report was retrieved from the literature; ten injuries were reported to the Consumer Product Safety Commission. Energies were determined by field trials and calculations. RESULTS: Injuries included periorbital edema and ecchymoses, orbital contusions and hematomas, maxillary sinus hematomas, facial hypesthesia, eyelid lacerations, subconjunctival hemorrhages, corneal edema and abrasions, hyphemas, traumatic iritis, iris sphincter ruptures, iris atrophy, angle recession, iridodialysis, traumatic cataract, vitreous hemorrhages, retinal hemorrhages, macular hole formation, optic atrophy, and bony orbital wall fractures. Epidemiologic analysis revealed that children and young adults, more often males, were injured, most commonly in the warm weather months. In field trials, maximum water balloon velocities ranged from 38 to 41 m/sec (85-92 mph) with kinetic energies from 176 to 245 joules; by calculation, maximum velocities ranged from 42 to 54 m/sec (95-121 mph) with kinetic energies from 141 to 232 joules. In a field demonstration, a slingshot-launched water balloon exploded a watermelon. CONCLUSION: Energies are comparable to or greater than those experienced with a variety of common objects, including some rifle bullets that are known to cause serious ophthalmic injuries. These energies are far in excess of those required to perforate a cornea, rupture a globe, or fracture the bony orbit. This study demonstrates the serious and potentially vision- and life-threatening injuries inflicted by these "toys."

Adolescent↗
PubMed1997

Psychobiology and psychopharmacotherapy of unipolar major depression: a review.

Psychopharmacology has continually informed the biological perspective of major depression. Antidepressants affect a variety of neurotransmitters by a wide range of pharmacological actions. The complexity of these neurotransmitter receptor interactions likely underlies the discrepancies observed in biochemical and physiological responses among apparently clinically homogenous depressive subgroups. This report provides an integrated review of the neuroendocrine and neurochemical perspectives of unipolar depression and how these advances influence the psychopharmacotherapy of unipolar major depression.

Antidepressive Agents↗
PubMed1997

Parotid saliva protein profiles in caries-free and caries-active adults.

OBJECTIVE: The objective of this study was to determine if there were any differences in the parotid saliva output and composition related to caries activity. STUDY DESIGN: Stimulated parotid saliva samples were collected from 85 healthy young adults, caries-active or caries-free. Flow rates were determined, and samples were analyzed for pH and buffer capacity, total protein, electrolytes, proteins with a high performance liquid chromatography method, and histatins. RESULTS: There were no differences in flow rates or pH, but buffer capacity was higher in women than in men, and K+ and Cl- were both slightly higher in the caries-active group. The women had a significantly higher total protein concentration, as well as higher concentrations of each of the individual protein components assayed. There were no differences attributable to caries activity. CONCLUSIONS: Significant sex differences in salivary protein concentrations exist. Caries activity may be related to some salivary electrolyte alterations, but not to protein composition.

Adolescent↗
PubMed1997

Bnm1, a Brassica pollen-specific gene.

cDNA and genomic clones of a new pollen-specific gene, Bnm1, have been isolated from Brassica napus cv. Topas. The gene contains an open reading frame of 546 bp and a single intron of 362 bp. A comparison of the deduced amino acid sequence with sequences in data banks did not show similarity with known proteins. Northern blot analysis of developing pollen showed that Bnm1 mRNA was first detected in bicellular pollen and accumulated to higher levels in tricellular pollen. Bnm1 mRNA was not detected in leaves, stems, roots, pistils, seeds or pollen-derived embryos. RNA in situ hybridization of whole flower buds confirmed that Bnm1 was pollen-specific and expressed late in development. A promoter fragment of the Bnm1 gene fused to the gusA reporter gene yielded similar patterns of tissue specificity and developmental regulation in transgenic B. napus cv. Westar plants; however, the promoter was also active during the early stages of pollen development. The Bnm1 gene, cloned in this study, was derived from the A genome of the allotetraploid species B. napus (AACC). Southern blot analysis indicated that sequences similar to the Bnm1 gene were found in both A and C Brassica genomes. Related sequences were found in all 10 members of the Brassiceae tribe examined, but were not present in all tribes of the Brassicaceae family.

Brassica↗
PubMed1997

Characterization of a mitomycin-binding drug resistance mechanism from the producing organism, Streptomyces lavendulae.

In an effort to characterize the diversity of mechanisms involved in cellular self-protection against the antitumor antibiotic mitomycin C (MC), DNA fragments from the producing organism (Streptomyces lavendulae) were introduced into Streptomyces lividans and transformants were selected for resistance to the drug. Subcloning of a 4.0-kb BclI fragment revealed the presence of an MC resistance determinant, mrd. Nucleotide sequence analysis identified an open reading frame consisting of 130 amino acids with a predicted molecular weight of 14,364. Transcriptional analysis revealed that mrd is expressed constitutively, with increased transcription in the presence of MC. Expression of mrd in Escherichia coli resulted in the synthesis of a soluble protein with an Mr of 14,400 that conferred high-level cellular resistance to MC and a series of structurally related natural products. Purified MRD was shown to function as a drug-binding protein that provides protection against cross-linking of DNA by preventing reductive activation of MC.

Amino Acid Sequence↗