Biomedical subjects

J T Irwin

Publications and source records attributed to J T Irwin.

10 recordsLinked to original sources

PubMed2004

Mitochondrial phylogeography of the moor frog, Rana arvalis.

The moor frog Rana arvalis is a lowland species with a broad Eurasiatic distribution, from arctic tundra through forest to the steppe zone. Its present-day range suggests that glacial refugia of this frog were located outside southern European peninsulas. We studied the species-wide phylogeographical pattern using sequence variation in a 682 base pairs fragment of mtDNA cytochrome b gene; 223 individuals from 73 localities were analysed. Two main clades, A and B, differing by c. 3.6% sequence divergence were detected. The A clade is further subdivided into two subclades, AI and AII differing by 1.0%. All three lineages are present in the Carpathian Basin (CB), whereas the rest of the species range, including huge expanses of Eurasian lowlands, are inhabited solely by the AI lineage. We infer that AII and B lineages survived several glacial cycles in the CB but did not expand, at least in the present interglacial, to the north. The geographical distribution and genealogical relationships between haplotypes from the AI lineage indicate that this group had two glacial refugia, one located in the eastern part of the CB and the other probably in southern Russia. Populations from both refugia contributed to the colonization of the western part of the range, whereas the eastern part was colonized from the eastern refugium only. The effective population size as evidenced by theta(ML) is an order of magnitude higher in the AI lineage than in the AII and B lineages. Demographic expansion was detected in all three lineages.

Animals↗

PubMed2001

Diapause development in frozen larvae of the goldenrod gall fly, Eurosta solidaginis fitch (diptera: tephritidae).

Seasonal changes in metabolic rate and the potential for morphological development demonstrated that third-instar larvae of the goldenrod gall fly, Eurosta solidaginis Fitch, exhibit a distinct winter diapause. Metabolic rate (CO2 production) was significantly lower from 15 October to 9 February than in early autumn (9 September) and spring (1 March) samples. The induction of diapause coincided with the development of cold-hardening, maximum larval mass, and gall senescence, but our experiments did not identify specific cues triggering diapause induction. We examined the influence of exposure to 0 degrees C and -20 degrees C on diapause development. Diapause development in larvae stored at 0 degrees C occurred at approximately the same rate as in nature. Until 15 December the larvae were in the refractory phase of diapause (incapable of morphological development, even at permissive temperatures), but afterward moved to the activated phase within which diapause intensity decreased until termination in February. Diapause development occurred in larvae collected during the winter and stored at -20 degrees C for periods of 1 week to 3 months. Diapause intensity decreased in frozen larvae through the winter but at a slower rate than in larvae stored at 0 degrees C.

Animals↗

PubMed1988

Interaction of phenol red with estrogenic and antiestrogenic action on growth of human breast cancer cells ZR-75-1 and T-47-D.

Studies reported here confirm that the pH indicator, phenol red, acts as a weak estrogen and reexamine the significance of estrogenic and antiestrogenic effects on growth of the human breast cancer cell lines ZR-75-1 and T-47-D in the absence of phenol red. Removal of phenol red reduces but does not immediately eliminate cell growth in the absence of estradiol. Basal cell growth can be reduced for T-47-D cells and eliminated for ZR-75-1 cells by prior growth in the absence of steroid and phenol red for 3 weeks, demonstrating that estrogens can have long lasting effects on cells in culture (termed "steroid memory") and that there exist both cells which are responsive (T-47-D) and dependent (ZR-75-1) on estradiol for growth. Antiestrogen action in these cell lines is affected by at least four parameters: (a) presence of phenol red; (b) time in culture; (c) cell density; (d) steroid memory effects. At high cell density, antiestrogens suppress phenol red-stimulated activity but have little effect in the absence of phenol red. However, at low cell density in the absence of phenol red, tamoxifen has a biphasic action: initial weak stimulation, later inhibition. trans-Hydroxytamoxifen does not stimulate but inhibition increases with time in culture. Following deprivation for 3 weeks of phenol red and steroid, antiestrogen action on ZR-75-1 cells at low density became much more inhibitory. Such responses to antiestrogens are discussed in relation to possible autocrine/paracrine growth regulation of the cells. Clinical relevance is suggested.

Breast Neoplasms↗

PubMed1988

Pulmonary microembolization in experimental aortic surgery.

Pulmonary dysfunction frequently follows major surgery and has many features identical to "shock lung'. A porcine model of aortic surgery is described in which 111In-labelled platelet kinetics were related to subsequent pulmonary function. In 14 pigs, standardized aortic surgery resulted in reproducible shock and a 50 per cent mortality at 3 days. Cardiac output fell from 2.3 +/- 0.2 to 1.0 +/- 0.1 litres min-1 following removal of the aortic clamp and mean platelet and leucocyte counts fell from 437 +/- 48 to 252 +/- 39 x 10(9) litres-1 and 21.7 +/- 1.5 to 12.9 +/- 1.2 x 10(9) litres-1 respectively (P less than 0.01). Aggregate levels in inferior vena caval blood were maximal at this time and radiolabelled platelets accumulated in the lung with a rise in pulmonary vascular resistance. Alveolar-arterial oxygen difference subsequently increased from initial values of 13.7 +/- 2.0 to 23.4 +/- 3.5 mmHg (P less than 0.01) following resuscitation and to 32.5 +/- 3.4 mmHg at 3 days following surgery (P less than 0.01). This clear sequence suggests that pulmonary platelet microembolization occurs during surgical shock and may be responsible for subsequent pulmonary dysfunction.

Animals↗

PubMed1986

Opsonic dysfunction secondary to plasma fibronectin depletion after aortic surgery.

Fibronectin is a plasma opsonin which is depleted after major injury or surgery. The effect of major aortic surgery on plasma fibronectin has been studied in patients and in an equivalent experimental model in pigs. On the day after aortic surgery in eleven patients mean fibronectin (+/- s.e.m.) had fallen from 363 +/- 11 mg/l pre-operatively to 179 +/- 19 mg/l (P less than 0.01). No such fall was observed in patients undergoing herniorrhaphy. In fourteen pigs aortic surgery produced reproducible surgical shock and a fall in plasma fibronectin from 331 +/- 10 mg/l to 43 +/- 13 mg/l after resuscitation (P less than 0.01). Whenever plasma fibronectin fell below 190 mg/l the circulating free fibronectin was consumed in complexes of 1000 kDa containing collagenous debris. More severe depletion of plasma fibronectin was related to higher concentrations of circulating nonopsonized collagenous debris and to subsequent mortality in pigs. The depletion of free fibronectin that occurs following major surgery may produce clinically important opsonic dysfunction. The clinical relevance of this fibronectin consumption may be missed if measurement is limited to circulating fibronectin levels without determining that proportion bound in complexes and no longer available as an opsonin.

Animals↗

PubMed1986

Effect of the cyclo-oxygenase inhibitor indobufen on platelet accumulation in prosthetic vascular grafts.

An in vivo method of measuring thrombus deposition and pseudo-intimal thickening in prosthetic arterial grafts in an animal model is described. The effect of indobufen, a new cyclo-oxygenase inhibitor, was evaluated and compared to aspirin plus dipyridamole and placebo in 24 greyhounds. Luminal platelet accumulation expressed as thrombogenicity index was 0.33 +/- 0.07 in the placebo group. This was significantly reduced to 0.14 +/- 0.01 by indobufen (P less than 0.05). The reduction to 0.19 +/- 0.04 by aspirin plus dipyridamole failed to achieve statistical significance. Pseudointimal thickness when measured 28 days after implacement was significantly reduced to 21.4 +/- 10.6 per cent by indobufen (P less than 0.01) and 29.4 +/- 10.6 per cent by aspirin plus dipyridamole (P less than 0.02) compared to 75 +/- 10 per cent found in the placebo group. This prosthetic graft model has considerable advantages in the evaluation of potential platelet inhibitory drugs for use in vascular surgery.

Animals↗

PubMed1986

Hypercholesterolaemia accentuates platelet activity.

Platelet aggregation response to collagen has been studied in 20 rabbits, randomly allocated to receive a normal (control) or high cholesterol diet. The sensitivity of platelets to collagen was significantly higher in the hypercholesterolaemic group (p less than 0.01) compared to controls. All hypercholesterolaemic rabbits developed generalised atherosclerosis and this may be due to increased circulating platelet activity.

Animals↗

PubMed1985

The effects of thromboxane antagonism on the transit time of platelets through the spleen.

The spleen is well-known as a site for platelet pooling, although the mechanisms controlling intrasplenic platelet transit are essentially unknown. We tested the possibility that thromboxane A2 might be involved in this control by measuring intrasplenic platelet transit time in 10 subjects receiving a specific thromboxane A2 receptor antagonist (AH23848B; 70 mg; Glaxo Group Research Ltd), in 10 receiving aspirin (300 mg) plus dipyridamole (75 mg), and in 9 receiving placebo. All doses were administered 3 times daily commencing 4 days prior to transit time measurement. Mean intrasplenic platelet transit time was measured by monitoring the kinetics of equilibration of 111In radiolabelled platelets between blood and spleen following intravenous injection. There was no difference between the mean transit time in the 3 groups of subjects, lending no support to the hypothesis that thromboxane A2 is involved in the control of platelet traffic through the spleen.

Aged↗

PubMed1979

Articular cartilage preservation and storage. I. Application of tissue culture techniques to the storage of viable articular cartilage.

Articular cartilage slice explants were stored under various conditions, including freezing-thawing at various rates by using dimethyl sulfoxide (DMSO) as a cryoprotective agent, incubating in standard tissue culture medium (MEM Eagle:NCTC 135:15% fetal calf serum) in 5% CO2 and air at 4 degrees, 21 degrees, and 37 degrees C, and incubating in standard tissue culture medium containing 200 micrograms/ml alpha-tocopherol (vitamin E) at 37 degrees C after first ascertaining a dose-response curve of vitamin E. Results indicated that articular cartilage slice explants did not survive freezing or storage at 4 degrees and 21 degrees C as measured by 35S uptake. When stored at 37 degrees C in standard tissue culture in 5% CO2 and air, the slice explants remained viable for up to 60 days. The addition of alpha-tocopherol to the medium resulted in significantly less release of previously incorporated 35Sin stored cartilage slices and significantly less reduction of the amount of hexosamine present in the stored explants. alpha-Tocopherol in the medium also preserved safranin O staining. Thus, the application of tissue culture techniques to the storage of articular cartilage made it possible to preserve cartilage slice explants in a viable, biochemically "normal" state.

Animals↗

PubMedDate not supplied

Freezing impairment of male reproductive behaviors of the freeze-tolerant wood frog, Rana sylvatica.

The wood frog (Rana sylvatica), a temperate-zone anuran that overwinters within the frost zone, is adapted to tolerate the freezing and thawing of its tissues. Because the effects of freezing on complex neurobehavioral function are unknown and because R. sylvatica encounters subfreezing temperatures during its late-winter breeding season, we investigated the reproductive behaviors and physiology of male frogs after freezing (minimum body temperature, -2 degrees C) and postthaw recovery (4 degrees C). In tests simulating conditions at the breeding pool, these frogs, which otherwise behaved normally, exhibited reduced mate-searching effort and fewer assaults on mates and did not amplex females until 16-24 h after thawing. Although amplectic ability was ultimately restored in most frogs, they competed poorly for mates against never frozen controls. Further study suggested that the level of behavioral impairment depends on the severity of the freezing exposure. During freezing, tissues accumulated large quantities of the cryoprotectant glucose and desiccated extensively, responses that promote freezing survival. Freezing also caused marked hydroosmotic and metabolic perturbations, which may have impaired neuro-behavioral function, perhaps by interfering with the processing of audio, visual, and tactile stimuli. Individuals that encounter subfreezing temperatures shortly before arriving at the breeding pools may incur reduced reproductive success.

Acclimatization↗