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Biomedical subjects

S J Wilson

Publications and source records attributed to S J Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Pathology of rhinitis and bronchial asthma.

Studies of the pathology of rhinitis and asthma have identified similarities and differences between these two clinical conditions. With regard to symptoms, both the nose and the lower airways respond to neural stimulation by irritant substances, but a major difference is that engorgement of the capacitance vessels is the main cause of nasal obstruction in rhinitis, while muscle constriction is the major determinant of lower airway narrowing. There are also similarities and differences with respect to the role of inflammatory cells. In both conditions there is evidence of allergen-induced mast cell activation, with production of an array of mediators (some mast cell-derived and others originating from a variety of other cell types). Eosinophilia is also characteristic of both diseases--it is prominent even in mild forms of asthma, but is low in pollen-sensitive rhinitics outside of the season. T-cell activation and production of cytokines plays an important role in the development and maintenance of allergic disease, but the level of T-cell activation may differ between asthma and rhinitis. Further research into differences in cellular activity and response to treatment between these two diseases may help define factors which will determine whether atopic disease is expressed in the upper, lower, or both parts of the respiratory tract.

Asthma↗
PubMed1996

Subjective effects of double gloves on surgical performance.

This randomised trial compared single gloves with combinations of double gloves to determine the subjective effects on comfort, sensitivity and dexterity in 32 surgeons. Glove perforation rates were also compared. Single gloves of the surgeon's normal size (method A) were used as control. Double gloves were worn in three different ways, selected randomly: normal gloves inside and gloves one-half size larger outside (method B); the larger gloves inside and the normal gloves outside (method C); and lastly, two pairs of gloves of normal size (method D). Double gloves by all three methods significantly protected against needle perforation of the inner gloves when compared with single gloves, but also significantly impaired comfort, sensitivity and dexterity. When the three types of double gloving were compared, there appeared to be advantages for method C for all modalities, but the differences did not reach statistical significance; also, more surgeons expressed a preference for method C. Perforation of the inner gloves was significantly less for double gloves than for single gloves. We conclude that double gloves often protect the surgeon against needle perforations, but are felt to impair comfort, sensitivity and dexterity.

Attitude of Health Personnel↗
PubMed1995

Defective G2 checkpoint function in cells from individuals with familial cancer syndromes.

The early events in the G2 checkpoint response to ionizing radiation (IR) were analyzed in diploid normal human fibroblasts (NHFs) and fibroblasts from patients with two heritable cancer syndromes. Exposure to gamma-radiation of asynchronously growing NHFs resulted in a rapid reduction in the number of cells in mitosis (G2 delay) and was accompanied by a quantitatively similar reduction in the p34CDC2/cyclin B in vitro histone H1 kinase activity as compared with sham-treated controls. This G2 delay was strong by 1 h following exposure to IR, maximal by 2 h, and was accompanied by an accumulation of tyrosine-phosphorylated p34CDC2 molecules. In contrast, fibroblasts from individuals with ataxia telangiectasia displayed significantly less reduction of the mitotic index or histone H1 kinase activity after IR. Low passage fibroblasts from individuals with Li-Fraumeni syndrome having one wild-type and one mutated p53 allele were similar to NHFs in their immediate G2 checkpoint response to IR, as were NHFs expressing the human papilloma virus type 16 E6 gene product (functionally inactivating p53) and low passage cells from p53-deficient mouse embryos. However, the p53-deficient fibroblasts were genomically unstable and became defective in their early G2 checkpoint response to IR. Furthermore, immortal Li-Fraumeni syndrome fibroblasts lacking wild-type p53 displayed an attenuated G2 checkpoint response. These results link the early events in G2 checkpoint response to IR in NHFs with a rapid inhibition of p34CDC2/cyclin B protein kinase activity and demonstrate that while not required for this immediate G2 delay, lack of p53 can lead to subsequent genetic alterations that result in defective G2 checkpoint function.

Ataxia Telangiectasia↗
PubMed1995

Xeroderma pigmentosum variant: generation and characterization of fibroblastic cell lines transformed with SV40 large T antigen.

Xeroderma pigmentosum variant (XPV) fibroblasts from the XP4BE strain (CRL1162) were transformed with the SV40 large T antigen with the purpose of generating immortalized cell lines that are defective in post-replication repair (PRR). Two transformation and selection protocols were used and at least two independent clones were obtained, which behaved in culture as immortal cell lines. Fingerprinting analyses were used to demonstrate their origin from XP4BE cells and to compare their genetic profiles. These cell lines were shown to be hypersensitive to killing by uv when compared to SV40-transformed fibroblasts derived from foreskins of normal neonates. One of the XPV transformed cell lines (CTag) was characterized further as a potential source of cell-free extracts with capability for catalyzing the T antigen-dependent in vitro replication of plasmid DNA carrying the SV40 origin of replication. In this assay system, CTag extracts were shown to be as active as those produced from HeLa cells. In vitro replication of uv-damaged plasmid DNA by protein extracts from PRR-defective (XPV) and PRR-proficient cells might allow the identification and characterization of protein factors that contribute to normal replication of uv-damaged DNA. Ultraviolet irradiation of plasmid DNA templates caused dose-dependent inhibition of in vitro replication by both HeLa and CTag extracts.

Antigens, Polyomavirus Transforming↗
PubMed1995

The effects of clonidine on cardiovascular responses to standing in healthy volunteers.

This study assessed the effects of clonidine on blood pressure (BP) and heart rate responses to active standing, recorded continuously using a Finapres monitor. Ten subjects were given a placebo infusion over 1 h, followed by clonidine hydrochloride 1.5 micrograms/kg over 2 h. During placebo and at 1, 3 and 19 h following the clonidine infusion, heart rate and blood pressure were recorded during the second half of supine rest for 10 min, active standing and quiet standing for 7 min. Clonidine did not alter the size of immediate drop in BP on standing, although the nadir was lower. BP recovery was impaired, with a loss of the usual BP overshoot in most subjects and with delays in reaching supine levels of diastolic BP (6.1 versus 9.6 s; p < 0.01) and systolic BP (8.1 versus 12.3 s; p < 0.05). The compensatory initial heart rate rise was significantly increased from 47 to 53 beats/min (p < 0.05), although the peak rate reached was reduced from 114 to 104 beats/min (p < 0.05). These results demonstrate that impairment of central sympathetic vasomotor drive leads to a delay in BP recovery and loss of initial BP overshoot immediately after standing, together with impaired maintenance of early steady-state BP.

Adult↗
PubMed1995

Use of selective serotonin reuptake inhibitors and other serotonergic drugs in the biological dissection of affective disorders.

The need to subtype patients with affective disorders on the basis of biological characteristics is well recognized, and much of the research in this area has focused on the serotonergic system. Biological subtyping can be approached using both peripheral and central markers. Peripheral markers include platelet serotonin concentrations, the density and affinity of platelet serotonin reuptake and platelet 5-HT2 receptors, and plasma serotonin concentrations. Central markers include cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations, and endocrine, psychological and body temperature responses to challenge tests with a number of serotonergic drugs. More recently, the role of selective serotonin reuptake inhibitors (SSRIs) and other serotonergic drugs in sleep, and in the control of cardiovascular homeostasis, has been studied. This may provide a greater understanding of the mechanisms of serotonin dysregulation in affective disorders, and may ultimately improve treatment of these conditions.

Biomarkers↗
PubMed1995

A comparison of the effects of phenelzine treatment with moclobemide treatment on cardiovascular reflexes.

The effects of treatment with phenelzine (n = 15) and moclobemide (n = 20) on heart rate variability and cardiovascular responses to standing were examined using non-invasive beat-to-beat blood pressure (BP) monitoring in an open cross-sectional study. Phenelzine markedly impaired the BP response compared with moclobemide, with 83% vs 15% of patients lacking the normal initial BP overshoot (p < 0.01). BP recovery to supine levels was delayed (median time for diastolic BP 14.5 s after phenelzine vs 4.9 s after moclobemide; p < 0.002). Standing BP at 1 min and its change from supine levels were also significantly lower in the phenelzine group (delta diastolic BP 4 mmHg vs 15 mmHg; p < 0.001). Heart rate responses and variability were preserved and did not differ between treatments. These findings are consistent with impairment of sympathetic function but preservation of parasympathetic responses after phenelzine treatment.

Adolescent↗
PubMed1995

Clinical impact of bacteria and fungi recovered only from broth cultures.

We prospectively evaluated 356 bacteria and fungi recovered from broth enrichment tubes from cultures with sterile direct plates to determine the clinical impact of isolates recovered only from broth cultures. These "broth only" isolates (BOI) were classified as contaminants or true on the basis of review of patient charts. True isolates were considered clinically relevant only if they altered or should have altered patient management. Of 356 BOI, 259 (73%) were considered contaminants (mostly coagulase-negative staphylococci and Propionibacterium spp.) and 97 (27%) were considered true. For individual microorganisms, 9 of 9 (100%) Staphylococcus aureus isolates, 13 of 13 (100%) members of the family Enterobacteriaceae, 10 of 12 (83%) fungi, 7 of 10 (70%) enterococci, 7 of 11 (64%) other gram-negative bacilli, 13 of 31 (45%) anaerobic bacteria, 10 of 24 (42%) streptococci, 22 of 140 (16%) coagulase-negative staphylococci, 6 of 92 (7%) Propionibacterium spp., and 0 of 14 (0%) diphtheroids and Bacillus spp. were classified as true. Eleven of 97 (11%) patients with true BOI had clinically relevant isolates. Fifty-nine of the 97 (61%) patients with true isolates already were on therapy, and no change was made because of the BOI. Six (6%) patients with contaminants received therapy for their BOI. We conclude that broth inoculated as an adjunct to direct plating seldom yields results that favorably alter patient management and could be omitted for most specimens without compromising patient care.

Adult↗
PubMed1994

p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest.

gamma-Irradiation of human diploid fibroblasts in the G1 interval caused arrest of the cell cycle prior to S phase. This cell cycle block was correlated with a lack of activation of both cyclin E-Cyclin-dependent kinase 2 (Cdk2) and cyclin A-Cdk2 kinases and depended on wild-type p53. Although the accumulation of cyclin A was strongly inhibited in gamma-irradiated cells, cyclin E accumulated and bound Cdk2 at normal levels but remained in an inactive state. We found that both whole-cell lysates and inactive cyclin E-Cdk2 complexes prepared from irradiated cells contained an activity capable of inactivating cyclin E-Cdk2 complexes. The protein responsible for this activity was shown to be p21CIP1/WAF1, recently described as a p53-inducible Cdk inhibitor. Our data suggest a model in which ionizing radiation confers G1 arrest via the p53-mediated induction of a Cdk inhibitor protein.

Base Sequence↗
PubMed1994

High resolution high field rodent cardiac imaging with flow enhancement suppression.

A method that incorporates cardiorespiratory-gated 2DFT spin-echo imaging with blood flow enhancement suppression is described which enables high resolution microimaging of the rodent heart. This methodology was applied to obtain in vivo cardiac mouse and rat images with in-plane resolutions of 100-200 microns using high field vertical bore magnet systems. Suppression of intraventricular blood flow enhancement was achieved using a combined spin-echo/gradient-refocussed sequence to dephase magnetization from flowing spins prior to imaging.

Animals↗
PubMed1994

G1 arrest and cell-cycle-dependent clastogenesis in UV-irradiated human fibroblasts.

The demonstrations of frequent allelic deletions in lung and colon cancers have reemphasized the importance of clastogenesis in carcinogenesis. We have investigated the mechanisms of induction of chromosome aberrations in ultraviolet-irradiated diploid human fibroblasts. Cells were irradiated with UV at various times during a parasynchronous wave of cell proliferation and then harvested during the first mitosis that followed irradiation. Metaphase spreads were stained with Geimsa and the yields of chromosome aberrations were quantified. Ultraviolet irradiation induced primarily chromatid-type chromosome aberrations which included chromatid breaks and exchanges. Frequencies of aberrations displayed significant differences according to the phase of the cell cycle in which irradiation occurred and the time after irradiation when metaphases were harvested. Fibroblasts that were irradiated when in G0 and then immediately replated to stimulate cell division and cells that were at the S/G2 border when irradiated displayed the fewest numbers of aberrations. For G0-irradiated cells, the first entering mitosis carried a higher frequency of aberrations than those collected 2-4 h later. In contrast, for S/G2-irradiated cells the first into mitosis displayed fewer aberrations than subsequent fractions. Cells that were irradiated when at the G1/S border displayed the greatest numbers of aberrations with the frequencies of chromatic exchanges being significantly increased over all other times of irradiation. These studies confirm that UV is an S-phase-dependent clastogen and point to the G1/S border as a time of maximal sensitivity to clastogenesis. Irradiation of G1 cells was shown to produce a fluence-dependent reduction in the rate of entry of cells into the S-phase. There appeared to be a point late in G1 beyond which cells were resistant to irradiation and experienced less delay in S phase entry. Ataxia telangiectasia fibroblasts failed to delay entry to S phase following UV-irradiation in G1 and displayed hypersensitivity to UV-induced chromosomal aberrations. The delay in entry of damaged cells into the S phase may have the beneficial effect of providing more time for repair of potentially clastogenic DNA damage before the onset of DNA replication.

Ataxia Telangiectasia↗
PubMed1994

A pharmacodynamic study of the alpha 2-adrenergic receptor antagonist ethoxyidazoxan in healthy volunteers.

Ethoxyidazoxan, a potent and highly selective alpha 2-adrenergic receptor antagonist, was administered intravenously to six healthy male volunteers in a double-blind, placebo-controlled, dose-rising design. Doses of 6 micrograms/kg and 8 micrograms/kg infused intravenously over 30 minutes produced significant elevations of plasma norepinephrine and body temperature and inhibited norepinephrine-induced platelet aggregation. Central activity was shown by reversal of the slowing of saccadic eye movements and an increase in saccade peak velocity at the higher dose. Modest increases in blood pressure were produced without change in heart rate. Ethoxyidazoxan was well tolerated, with slight changes in subjective alertness and sedation.

Adrenergic alpha-Antagonists↗
PubMed1994

Successful treatment of night terrors and somnambulism with paroxetine.

A patient with a 30-year history of somnambulism and night terrors is described. The use of a home ambulatory sleep electroencephalogram (EEG) recording in clarifying the diagnosis and in monitoring the results of treatment is illustrated and successful treatment using a selective serotonin re-uptake inhibitor is reported.

Clonazepam↗
PubMed1994

Effect of melengestrol acetate (MGA) or progesterone-releasing intravaginal device (PRID) on follicular development, concentrations of estradiol-17 beta and progesterone, and luteinizing hormone release during an artificially lengthened bovine estrous cycle.

Two trials were conducted to determine whether 7-d progestogen treatment beginning on d 17 of the estrous cycle altered 1) ovarian follicular development, 2) serum concentration of estradiol-17 beta (E2) and progesterone (P4), and 3) patterns of release of luteinizing hormone (LH). In both trials, Angus, Angus x Holstein, or Holstein cows 2 to 6 yr of age were randomly assigned to receive either melengestrol acetate (MGA, .5 mg.animal-1.d-1; n = 23), a progesterone-releaseing intravaginal device (PRID, n = 26) or to serve as untreated Controls (n = 14). Ultrasonography and blood sampling were performed daily throughout the experiment beginning on d 3 (Trial 1) or d 9 (Trial 2) of the estrous cycle. In Trial 2, blood samples were collected every 15-min for 6 h on d 17 (all cows) and d 20 and 23 (MGA and PRID cows) for determination of LH. Estrous cycle length was 3 to 5 d greater (P < .05) for MGA- and PRID-treated cows characterized by two (MGA-2 and PRID-2) or three (MGA-3 and PRID-3) dominant follicles than for control cows exhibiting two (Control-2) or three (Control-3) dominant follicles. A greater proportion (P < .05) of MGA- than of PRID-treated cows ovulated the follicle that was dominant at the beginning of treatment on d 17 (10 of 23 vs 1 of 26). Serum P4 concentrations declined 3 d earlier in Control-2 and MGA-2 cows than in Control-3, MGA-3 or PRID-3 cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravaginal↗
PubMed1993

Formation of myotubes in aneural rat muscles.

Skeletal muscles formed in the absence of innervation are deficient in number of fibers, atrophic, and prone to degeneration. We and others have suggested that primary myotubes form autonomously, and the major effect of embryonic denervation is to halt the formation of secondary myotubes by removing the mitotic stimulus for generation of their precursor myoblasts. This hypothesis has recently been put into question by the results of work by Condon et al. (Dev. Biol., 138, 275-295, 1990) and by B. J. Fredette and L. T. Landmesser (Dev. Biol. 143, 19-35, 1991) who propose that lowered secondary myotube numbers are at least in part due to absence of the primary myotubes which would normally serve as scaffold for their formation. We distinguish between these hypotheses by studying generation and degeneration of primary myotubes and formation of secondary myotubes in fetal rat muscles denervated by injection of beta-bungarotoxin at different times between Embryonic Days (E) 14 and 17. Denervation at any of these times reduced primary myotube numbers on E18 to about 80% of control. Despite this modest decrease in primary myotube numbers, secondary myotube generation fell to below 3% of normal in extensor digitorum longus (EDL) muscles denervated on E14 or E15 and to below 12% of control in soleus muscles denervated on E14-E16. Secondary myotubes were associated with degenerating as well as intact primary myotubes. More secondary myotubes were generated only if nerves had been present up until E16 for EDL or E17 for soleus. We suggest that these observations of a critical period until E16 (EDL) or E17 (soleus) during which innervation is an absolute prerequisite for secondary myotube formation reflect the presence of a nerve-dependent population of myoblasts which must be activated before secondary myotube formation can commence.

Animals↗
PubMed1993

Formation of primary and secondary myotubes in aneural muscles in the mouse mutant peroneal muscular atrophy.

The role of motor innervation in supporting and regulating muscle development was studied using aneural muscles in the hindlimb of the mouse mutant peroneal muscular atrophy (pma). This is a single-locus autosomal mutation where homozygous animals lack the common peroneal nerve, so that muscles in the anterolateral compartment of the lower leg develop entirely without innervation. In adults, these muscles are extremely atrophied, and the mice display a clubfoot deformity. The mutant animals provide a preparation in which aspects of muscle formation can be studied in muscles that have never been exposed to direct contact with somatic motor or sensory axons, without pharmacological or surgical intervention. Using quantitative electron microscopy, we found that normal numbers of primary myotubes formed in aneural pma EDL muscles, but a greater than normal proportion degenerated during the first 2 days after their formation. Secondary myotubes appeared at their normal time and position within the muscle, initially in normal numbers, so that the ratio of secondary to primary myotubes initially was greater in pma than in CF1 control strain mice. No abnormalities in ultrastructure were seen until the time of birth, when retardation in development was obvious, together with invading macrophages and degenerating myofibres. The results show that secondary myotube formation in the mouse, as in the chick (B. J. Fredette and L. T. Landmesser, Dev. Biol. 143, 19-35, 1991) is not directly dependent on innervation. In control muscles, secondary myotubes first form in the vicinity of endplates on primary myotubes. No aggregations of ACh receptors or acetylcholinesterase were present in the aneural muscles, showing that these are neurally induced in the mouse, but secondary myotubes formed in their normal position indicating that positional information related to endplate formation is present in aneural muscles.

Acetylcholinesterase↗