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D Cox

Publications and source records attributed to D Cox.

At least 109 records · Page 6Linked to original sources
PubMed1994

Expression of TGF-beta s and TGF-beta type II receptor mRNAs in mouse folliculogenesis: stored maternal TGF-beta 2 message in oocytes.

The present in situ hybridisation study describes expression of TGF-beta 1, TGF-beta 2, TGF-beta 3, and TGF-beta type II receptor mRNA during follicular development, and the temporal pattern and abundance of TGF-beta 2 transcripts in early pre-implantation embryos. TGF-beta 1 hybridisation signals were most prominent in the outer granulosa cell layers of the post-antral follicles and in the corpus luteum, whereas strong expression of TGF-beta type II receptor mRNA was confined to thecal cells. Weak TGF-beta 3 mRNA expression was observed in all major cell types of pre- and post-antral follicles. Most notably, the very strong TGF-beta 2 hybridisation signals which were detected in developing oocytes declined rapidly following fertilization. Although still abundant in two-cell embryos, TGF-beta 2 hybridisation signals were barely detectable in four- and eight-cell embryos. These findings, and the presence of specific sequence motifs in the 3' untranslated region of TGF-beta 2 mRNAs, suggest that TGF-beta 2 transcripts are stored as maternal messages.

Animals↗
PubMed1994

Antigen-induced release of macrophage activating factor from rainbow trout Oncorhynchus mykiss leucocytes.

The production of macrophage-activating factor (MAF) by rainbow trout, Oncorhynchus mykiss, head kidney leucocytes at varying times post-immunisation, with the fish bacterial pathogen, Aeromonas salmonicida, was investigated and correlated with head kidney lymphocyte proliferation and serum antibody production. MAF production was preceded by lymphocyte proliferation and both responses were highest using whole bacterial cells as the in vitro stimulant. MAF production and antibody production increased 2-3 weeks post-immunisation, and peaked 4-5 weeks post-immunisation. The relative importance of MAF activated phagocytes in the immunological armoury of disease-resistant, vaccinated fish requires further investigation.

Aeromonas↗
PubMed1994

The type I interferon system is locally activated in psoriatic lesions.

The expression of mRNAs encoding interferons (IFNs) and IFN-inducible proteins has been studied in psoriatic lesions and in noninvolved skin. The specific mRNAs have been detected by in situ hybridization using antisense RNAs. Signals for the expression of IFN-gamma mRNA have been found exclusively in cells of psoriatic lesions, and most likely represent a subpopulation of infiltrating leukocytes. Weak signals of IFN-alpha mRNA have been detected throughout the hyperkeratotic epidermis, although specific signals for IFN-beta mRNA expression were not detectable. The expression of two IFN-alpha-inducible gene products, namely the MxA protein and the 2'-5' oligoadenylate (2-5A) synthetase, have been studied as markers for the local activation of the IFN-alpha system. Expression of MxA mRNA and protein was observed in psoriatic keratinocytes, but not in normal appearing keratinocytes adjacent to the lesions. Similarly, 2-5A synthetase expression was markedly elevated in psoriatic keratinocytes. The results of the present study indicate that the IFN-alpha system is selectively activated in psoriatic lesions, although it remains silent in noninvolved skin. The implications of this finding are discussed within the boundaries of current understanding of the cytokine network.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Alpha 1-antitrypsin protects neonatal rats from pulmonary vascular and parenchymal effects of oxygen toxicity.

We investigated whether alpha 1-antitrypsin (alpha 1-AT) might protect neonatal rats from the pulmonary parenchymal and vascular effects resulting from hyperoxic exposure. Neonatal rats born into and maintained in hyperoxia (60% fraction of inspired oxygen) or room air were injected with a loading dose of alpha 1-AT (72 mg/kg) followed by 36 mg/kg every 72 h or with vehicle during the first 14 d of life. At the end of the experimental period, we measured body weight, lung compliance, lung volume, alveoli per mm2, and total number of alveoli and assessed right ventricular hypertrophy and vascular changes consisting of medial hypertrophy, muscular extension into peripheral, normally nonmuscular arteries, and number of peripheral arteries relative to alveoli. Our data show that alpha 1-AT treatment prevented the reduced lung compliance observed in the untreated hyperoxia-exposed neonatal rats, as well as the right ventricular hypertrophy and the associated vascular changes of medial hypertrophy of muscular arteries and muscularization of distal arteries. Reduced lung compliance in the hyperoxic but alpha 1-AT-untreated rats was associated with a reduction in lung elastin compared with room-air or alpha 1-AT-treated rats. In room-air rats, alpha 1-AT treatment increased lung compliance but also reduced the number of arteries relative to the number of alveoli, a feature that was not, however, associated with right ventricular hypertrophy. Our data suggest that supplemental alpha 1-AT might restore the imbalance in elastolytic activity induced by hyperoxia and thereby alleviate the toxic effects on lung parenchymal and vascular development.

Animals↗
PubMed1994

Efficacy study of THINKable in the attention and memory retraining of traumatically head-injured patients.

The efficacy of computer-assisted attention and memory retraining was evaluated with 15 severely head-injured patients. Training with selected exercises tailored to the individual's needs were provided from the THINKable program for up to 20 hours in both the attention and memory remediation modules. The experimental design evaluated outcome by juxtaposing multiple baseline procedures with a pre- and post-group comparison. Significant results were documented on the computerized tasks, psychometric measures and on patient and observer ratings of everyday behaviours of attention and memory.

Adolescent↗
PubMed1994

Endurance athletes' stroke volume does not plateau: major advantage is diastolic function.

Left ventricular function was examined during incremental work rates to maximum using simultaneous determinations of stroke volume, left ventricular ejection time (LVET), and diastolic filling time (DT). Seven endurance trained and seven untrained young adult males were studied on a cycle ergometer at matched heart rates of 90, 120, 140, 160, 180, and 190 bpm (+/- 1 bpm). Stroke volume of the untrained subjects reached a plateau at 120 bpm, but stroke volume of the trained subjects continued to increase to their maximum heart rate with no plateau. Throughout incremental work rates, LVET was significantly longer and DT was significantly shorter in the trained subjects. At a heart rate of 190 bpm, the corresponding rates of ventricular emptying and ventricular filling of the trained versus the untrained subjects were 20% and 71% greater, respectively (P < 0.01). We conclude that during incremental work rates the stroke volume of endurance trained athletes increases progressively to maximum with no plateau. In addition, although trained athletes rely on enhancements in both ventricular filling and ventricular emptying to augment stroke volume, by far their major advantage over untrained subjects is in ventricular filling.

Adult↗
PubMed1994

Higher incidence of peritonitis in native Canadians on continuous ambulatory peritoneal dialysis.

OBJECTIVE: To determine if the rate of peritoneal dialysis (PD)-related infections in our large Native population was higher than in non-Natives. DESIGN: Prospective study of PD-related infections, 1987 to 1993. PATIENTS: Forty-eight Natives and 136 non-Natives were studied. Comparisons of infection rates were made as well as determinations of the effect of diabetes and of dialysis techniques on infection rate. RESULTS: The chance of remaining free of peritonitis was far lower at 6 and 12 months in Natives versus non-Natives, 40% versus 76% at 6 months, and 24% versus 54% at 12 months (p < 0.01). Having diabetes or adding intraperitoneal insulin did not confer additional risk of peritonitis. The Y-line reduced the risk of peritonitis in non-Natives only. Exit-site infection (ESI) was significantly higher in Natives versus non-Natives, 0.42 versus 0.19 episodes per patient year (p < 0.01) mainly due to Staph. aureus. However, less than 30% of episodes of peritonitis were due to that organism. Staph. epidermidis peritonitis episodes were not more common in Native patients, whereas infections due to most other organisms were. CONCLUSION: The susceptibility to both peritonitis and exit-site infection is increased in Native Canadians compared to non-Natives. The nonprotective effect of the Y-line combined with increased peritonitis due to most organisms except Staph. epidermidis in Natives suggests that host factors could be important in these patients.

Adult↗
PubMed1993

Initial effects of the grounding of the tanker Braer on health in Shetland. The Shetland Health Study Group.

OBJECTIVE: To determine if the oil spillage from the tanker Braer had any immediate health effects on the exposed resident population. DESIGN: Cohort study with a comparison against controls, exposure status being assigned on the basis of geographical location. SETTING: Rural Shetland. SUBJECTS: All those resident on or after 5 January 1993 (day 0) within 4.5 km of the site of tanker's grounding. Controls matched for sex and age were drawn from a general practice list 95 km distant. OUTCOME MEASURES: Demographic details; smoking and alcohol consumption; perception of health and reported presence or absence of specific symptoms; peak expiratory flow; results of haematology, liver and renal function tests, and blood and urine toxicology. RESULTS: Of subjects contacted, 420 (66%) exposed people and 92 (68%) controls were studied; 56 non-attenders were surveyed. Principal health effects arose on days 1 and 2 and were headache, throat irritation, and itchy eyes. No significant differences between those exposed and controls were found for any of the biological markers. Toxicological studies did not show any exposures that are known to affect human health. CONCLUSIONS: The study confirmed the anecdotal reports of certain acute symptoms. No evidence of pulmonary, haematological, renal, or hepatic damage was detected at the population level. Toxicological samples from exposed people did not find levels known to affect human health. Further studies are required to ascertain whether there have been any long term effects on the population.

Acute Disease↗
PubMed1993

Injury induced expression of TGF-beta 1 mRNA is enhanced by exogenously applied TGF-beta S.

We have analysed and compared, by in situ hybridisation, the effects of exogenously applied TGF-beta s on expression of endogenous TGF-beta mRNAs in partial thickness thermal wounds in old and young mice. Although injury induced the expression of TGF-beta 1 mRNA in the epidermis and dermis at the wound margins, expression of TGF-beta 2- or TGF-beta 3-mRNA was not detected. Biopsies taken 24 hours following injury revealed a focally clustered distribution of TGF-beta 1 hybridisation signals in the dermis, the number of positive cells and expression levels being reduced in old mice. Topical application of all three TGF-beta isoforms enhanced TGF-beta 1 mRNA expression in the dermis of old and young mice. In biopsies taken three days following injury, TGF-beta 1 hybridisation signals were most prominent in the regenerating epidermis although at this timepoint differences in expression levels between treated and non-treated animals were less pronounced.

Animals↗
PubMed1993

TGF-beta s and TGF-beta type II receptor in human epidermis: differential expression in acute and chronic skin wounds.

Exogenously applied transforming growth factor-beta (TGF-beta) isoforms enhance wound healing processes in animal models; however, little is known about the expression of endogenous TGF-beta s and TGF-beta receptors in intact human skin or during wound healing. The present study has revealed several unexpected findings by means of in situ hybridization and immunohistology techniques. In humans, TGF-beta 3 is constitutively expressed in the epidermis of intact skin and in that of acute and chronic wounds--a pattern of expression closely mirrored by the TGF-beta type II receptor. Although not detected in intact skin, TGF-beta 1 mRNA expression was observed in the regenerating epidermis of acute (thermal) wounds but was not found in chronic decubital (pressure) wounds. TGF-beta 2 mRNA expression was not detected in the epidermis of any human skin or wound biopsies. From these findings we suggest that constitutive expression of TGF-beta 3 is important for maintenance of epidermal differentiation and that an induction of TGF-beta 1 expression is essential for re-epithelialization of human skin wounds. Lack of TGF-beta 1 expression in chronic pressure wounds may be associated with their protracted healing tendencies.

Adult↗
PubMed1993

In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis.

The purpose of this study was to investigate and to compare, by in situ hybridization, gene expression of IL-1 beta, IL-8, TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-alpha, p53 and c-myc in lesions and in non-involved skin of patients with psoriasis. All lesional skin biopsies showed overexpression of IL-1 beta, IL-8 TGF-alpha mRNAs. IL-1 beta hybridization signals were strong in a small number of cells localized predominantly in the dermal papillae and in the suprapapillary epidermis. Overexpression of TGF-alpha was observed in all suprabasal keratinocytes, whereas strongly elevated IL-8 mRNA expression was found to be restricted to clusters of suprabasal keratinocytes. TGF-beta 3, p53 and c-myc transcripts were clearly detected in the epidermis of all biopsies, although expression levels were comparable in lesional and non-lesional skin.

Cytokines↗
PubMed1993

The effects of evening primrose oil on nerve function and capillarization in streptozotocin-diabetic rats: modulation by the cyclo-oxygenase inhibitor flurbiprofen.

1. The aims of this study were first, to examine whether deficits in nerve conduction in streptozotocin-diabetic rats could be reversed by a 10% dietary supplement of evening primrose oil. Second, to determine the time-course of reversal, and third, to assess whether the effects could be blocked by the cyclo-oxygenase inhibitor flurbiprofen (5 mg kg-1 day-1). 2. One-month diabetes produced 20% and 15% deficits in sciatic motor and saphenous sensory conduction velocity respectively, which were maintained over 2 months diabetes. 3. The effect of 1-month evening primrose oil treatment on abnormalities caused by an initial month of untreated diabetes was examined. Motor and sensory nerve conduction velocity were restored to the non-diabetic level. 4. Resistance to hypoxic conduction failure was investigated for sciatic nerve trunk in vitro. The 80% conduction failure times were 29% and 55% prolonged by 1- and 2-month diabetes respectively. Evening primrose oil did not reverse the increased hypoxic resistance following 1-month untreated diabetes. 5. Sciatic nerve endoneurial capillary density was not significantly affected by diabetes, but was 16% increased in diabetic rats with reversal by evening primrose oil treatment for 1 month compared to 2-month untreated diabetes. 6. Serial motor conduction velocity measurement after 3-month untreated diabetes revealed complete normalization by evening primrose oil within 4 days. Cessation of treatment resulted in a rapid decline in conduction velocity over 24 h. 7. In a preventive study of 2-month duration, 6 groups of rats were used. These comprised non-diabetic controls, diabetic rats, and evening primrose oil-treated diabetic rats, both with and without flurbiprofen treatment. Flurbiprofen had no significant effect in non-diabetic rats, but produced an 11% worsening of motor conduction velocity and a 21% reduction of sciatic capillary density in diabetic rats. Evening primrose oil prevented the decreases in conduction velocity and increased hypoxic resistance with diabetes, and caused a 23% increase in capillary density. Flurbiprofen completely blocked the effect of evening primrose oil on conduction velocity, resistance to hypoxia, and capillarization.8. Six main conclusions were reached. First, evening primrose oil rapidly reverses conduction deficits in diabetic rats. Second, the effects of treatment may be very short-lived, suggesting a primary metabolic action. Third, evening primrose oil cannot reverse established changes in hypoxic resistance over 1-month treatment. Fourth, long-term treatment causes angiogenesis, suggesting a vascular action. Fifth,products of cyclo-oxygenase-mediated metabolism are necessary for maintaining vasa nervorum integrity in diabetic rats. Sixth, evening primrose oil probably acts by providing substrate for vasodilator prostanoid synthesis by vasa nervorum.

Action Potentials↗
PubMed1993

Elevation of serum phosphate affects parathyroid hormone levels in only 50% of hemodialysis patients, which is unrelated to changes in serum calcium.

Hyperphosphatemia is said to cause hyperparathyroidism either by depressing the plasma levels of ionized calcium and/or by affecting serum 1,25(OH)2 vitamin D3 levels. Direct evidence that hyperphosphatemia contributes to hyperparathyroidism in hemodialysis patients is unclear because previous published data are with older parathyroid hormone (PTH) assays. Phosphate was added to the dialysate of 15 patients for 12 wk whose predialysis serum phosphates were between 1.5 and 1.9 mM (4.7 to 5.9 mg/dL) in order to further increase their serum phosphate by 0.75 mM (2.4 mg/dL) without adjustments in other medications. No patient was on vitamin D therapy. In half of the patients, PTH levels remained unchanged (nonresponders; 214 +/- 64 versus 219 +/- 60 ng/L), whereas in the other patients, PTH rose from 204 +/- 53 to 338 +/- 60 ng/L (P < 0.05; responders). The degree of induced hyperphosphatemia was virtually identical in both groups, 1.7 mM increasing to 2.4 mM. Ionized calcium was unchanged in both groups after phosphate. Plasma 1,25(OH)2 vitamin D3 levels were low to start with and remained low throughout. Nonresponders had been on dialysis twice as long as responders and had consumed over seven times more aluminum salts. Nonresponders had higher postdeferoxamine increments in plasma aluminum (3,588 +/- 1,466 versus 603 +/- 390; P < 0.05), although neither these amounts nor plasma levels were in the toxic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1992

Pentamidine: a non-peptide GPIIb/IIIa antagonist--in vitro studies on platelets from humans and other species.

In this paper we show that the non-peptide anti-parasite agent pentamidine is a broad spectrum anti-platelet agent with an IC50 of 1.1 microM in ADP-induced platelet aggregation in human platelet rich plasma (PRP). It had similar activity when collagen, arachidonic acid, platelet activating factor, thrombin and epinephrine were used. It had no effect on platelet intracellular cAMP levels. It inhibited 125I-fibrinogen, 125I-fibronectin and 125I-von Willebrand factor binding to ADP-activated fixed platelets with IC50 values of 160, 160 and 60 nM respectively. Pentamidine showed a high degree of species selectivity with slightly less activity in monkey and dog PRP and little activity in guinea pig, rabbit, rat and mouse PRP compared with human. This was similar to the other RGD analogues tested. This species specificity was shown to be dependent on the species of platelets and independent of the species of fibrinogen. Thus, pentamidine is a potent non-peptide inhibitor of fibrinogen binding to GPIIb/IIIa.

Amino Acid Sequence↗
PubMed1992

Quality of life measures in health care. I: Applications and issues in assessment.

Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.

Clinical Protocols↗