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Biomedical subjects

A Sinclair

Publications and source records attributed to A Sinclair.

At least 37 records · Page 2Linked to original sources
PubMed1999

Breasts, babies and universities--reflections of two lactating professors.

This is a transcript of a presentation made by Mary E Black and Amanda Sinclair at the "Winds of Change" conference in Sydney on July 12, 1998. This was an international conference looking at issues around women in universities. It is reprinted here as many of the issues are of relevance to the readers of this journal. Both Mary and Amanda are experienced nursing mothers who also have high profile careers and are strongly committed to their families. In a sense they are pioneers as they speak openly about the conflicts both internal and external that they encounter. They were both asked to fly to Sydney to present this paper but decided not to, citing family responsibilities. Instead they persuaded the conference organisers to fund them to produce a video, shot in both Cairns and Melbourne and later edited into a presentation. This was shown to acclaim at the conference and provoked a lively discussion. If organisations are creative, they can do things differently and thus ensure that nursing mothers can fully participate in professional life.

Australia↗
PubMed1999

Lipoprotein(a), essential fatty acid status and lipoprotein lipids in female Australian vegetarians.

In the present study we investigated serum lipoprotein(a) [Lp(a)] levels, plasma lipids, the serum phospholipid polyunsaturated fatty acid profile and correlates of serum Lp(a) in healthy free-living female vegetarians (n=50) and omnivores (n=24) to assess differences which may have implications for cardiovascular risk. Dietary saturated fat and total plasma cholesterol were significantly lower in the vegetarians compared with omnivores. The mean serum Lp(a) concentration was lower in the vegetarians (171 mg/l) than in the omnivores (247 mg/l). The serum Lp(a) concentration was significantly negatively correlated with carbohydrate intake (as % of energy), and positively correlated with plasma total cholesterol. Compared with the omnivores, the vegetarians had significantly lower concentrations of 20:3,n-6, 20:4,n-6, 22:5,n-6, 20:5,n-3, 22:6,n-3 and total n-6 and n-3 polyunsaturated fatty acids, and a lower n-3/n-6 polyunsaturated fatty acid ratio, in serum phospholipids. Lower concentrations of plasma total cholesterol, serum phospholipid total fatty acids, total saturated fatty acids and arachidonic acid, and a tendency towards a lower serum Lp(a) concentration, in vegetarians may have beneficial effects on cardiovascular disease risk. However, the decreased concentration of serum phospholipid n-3 polyunsaturated fatty acids may potentially promote thrombotic risk. Based on the present data, it would seem appropriate for omnivores to reduce their dietary intake of total fat and saturated fat in order to decrease their plasma cholesterol, and vegetarians should perhaps increase their dietary intake of n-3 polyunsaturated fatty acids, and thus improve the balance of n-3/n-6, in order to reduce any thrombotic tendency that might increase their generally low risk of cardiovascular disease.

Adult↗
PubMed1998

Influences on adrenaline-induced thermogenesis in obese women and relationship to cardiovascular responses.

1. In order to evaluate factors influencing thermogenesis in obesity, energy expenditure was measured before and during an adrenaline infusion (25 ng min-1 kg-1 ideal body weight for 30 min) in 22 obese females. 2. Thermogenic responses were related to body morphology, age and biochemistry. In addition, thermogenic responses were related to cardiovascular responses by simultaneously measuring blood pressure, pulse rate and cardiac output using Doppler sonography. 3. Resting energy expenditure was predicted by body weight, lean body mass and fat mass. 4. Adrenaline-induced thermogenesis was predicted by fasting insulin, low basal respiratory quotient and body fat. 5. There was a significant relationship between the cardiac output and thermogenic responses to adrenaline (r = 0.63 P < 0.015) but there was no relationship to the heart rate or blood pressure responses. For every 1% increase in energy expenditure, there was a 5% increase in cardiac output. 6. In conclusion, the factors predicting resting energy expenditure and adrenaline-induced thermogenesis are different. Increased lipid oxidation and central fat distribution (with hyperinsulinaemia) are associated with a greater thermogenic response. The proportionately greater cardiac output responses may have implications for thermogenic agents designed to induce weight loss.

Adult↗
PubMed1997

The effect of short-term diets rich in fish, red meat, or white meat on thromboxane and prostacyclin synthesis in humans.

Foods which increase tissue arachidonic acid levels have been proposed to increase thrombosis tendency, presumably through increased platelet aggregation. This study examined the effect of doubling the dietary arachidonic acid (20:4n-6) using meat- or fish-based diets on the systemic production of prostacyclin (PGI2) and thromboxane (TXA2) in 29 healthy, nonsmoking adults. There were three, 3-wk low-fat dietary periods (< 15% energy as fat) in which subjects consumed a vegetarian diet for 1 wk followed by 2 wk on diets containing meat or fish as sources of 20:4n-6. Between each diet period, there was a 3-wk washout period, during which subjects returned to their normal diets. The level of 20:4n-6 consumed during the last 2 wk of each study was approximately double the usual intake (mean 140 mg/d), while the mean eicosapentaenoic acid (20:5n-3) content of the diets varied from 1 mg/d on the white meat diet to 70 mg/d on the red meat diet and to 847 mg/d on the fish diet. The serum phospholipid (PL) 20:4n-6/20:5n-3 ratios were 11:1 on the vegetarian diet, 15:1 on the white meat diet, 8:1 on the red meat diet, and 2:1 on the fish diet (P < 0.001). Neither white nor red meat diets affected platelet 20:4n-6 levels, platelet aggregation, ex vivo platelet TXB2 production, or the systemic PGI2 or TXA2 production as measured by gas chromatography-mass spectrometry analysis of the excretion levels of the principal urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and 11-dehydro-TXB2 (TXA2-M), respectively. The fish diet decreased the 20:4n-6/20:5n-3 ratio in platelet PL from the baseline level of 45:1 to 13:1 (P < 0.001), had no effects on platelet aggregation, but significantly decreased platelet TXB2 production (collagen-stimulated) and TXA2-M production, while PGI2-M levels were unaltered. These results indicate that short-term diets which double the usual 20:4n-6 intake using white meat (175-330 g/d) or red meat (275-530 g/d) are not associated with an increased TXA2 production, but this does not rule out the adverse effects of 20:4n-6 at higher levels in the diet, or for more prolonged periods. Short-term diets containing fish (100-200 g/d with 90-210 mg/d 20:4n-6 and approximately 650-1000 mg/d 20:5n-3) led to significant increases in platelet 20:5n-3 levels and a decrease in the ex vivo and systemic TXA2 production.

Adult↗
PubMed1997

Expression of the Ly-6E.1 (Sca-1) transgene in adult hematopoietic stem cells and the developing mouse embryo.

The mouse hematopoietic marker Sca-1, encoded by the Ly-6E.1 and Ly-6A.2 genes, has been instrumental in the enrichment and characterization of the stem cell for the adult blood system. In the studies reported here, we use Ly-6E.1 genomic fragments to direct expression of a lacZ marker transgene in vivo to study Ly-6E.1 specific regulatory elements in the hematopoietic stem cell and to localize these cells in the developing mouse embryo. We demonstrate that a region approximately 9 kb downstream from the transcriptional start site is required for the distinct, restricted expression pattern of the Ly-6E.1-lacZ transgene within adult hematopoietic stem cells and embryos. We also demonstrate that viable and functional lacZ-expressing hematopoietic stem cells can be enriched by FDG staining and flow cytometric sorting. The Ly-6E.1-lacZ-mediated enrichment of hematopoietic stem cells from adult transgenic bone marrow in combination with the temporal expression pattern of the transgene in the pro/mesonephros suggest an intraembryonic site of development for these cells in the mouse.

Animals↗
PubMed1996

Long chain polyunsaturated fatty acids and visual function in preterm infants.

Electroretinograms (ERG) were recorded at 40 weeks post-conceptual age (PCA) in 18 infants born prematurely (25-32 weeks gestation). Fatty acid composition of plasma and red cell phospholipids was measured within 4 days of birth and at time of ERG testing, and detailed record was kept of dietary intake. Correlations were seen between percentage intake of breast milk and docosahexaenoic acid (DHA) in both plasma (r = 0.818, P < 0.0001) and red cells (r = 0.534, P = 0.035) and significant differences in fatty acid profiles were seen between infants receiving > 50% and < 50% breast milk. No difference was seen in retinal sensitivity between infants receiving > 50% or < 50% breast milk. A positive correlation was seen between scotopic (rod) b-wave implicit time on ERG and DHA in both plasma (r = 0.733, P = 0.001) and red cells (r = 0.502, P = 0.04). A positive correlation was seen between arachidonic acid and rod ERG amplitude (r = 0.565, P = 0.022) which may reflect the higher AA/DHA ratio in the developing retina. These data did not support our hypothesis that increased dietary DHA results in enhanced retinal maturation. Visual acuity measured at 40 weeks PCA and again 3 months later was similar between groups. While subtle relationships were demonstrated between long chain polyunsaturated fatty acids and visual function, all infants were felt to be within age-appropriate normal range at expected date of delivery and at 3 months corrected age.

Breast Feeding↗
PubMed1996

The Ly-6E.1 (Sca-1) gene requires a 3' chromatin-dependent region for high-level gamma-interferon-induced hematopoietic cell expression.

The Ly-6E.1/A.2 gene product recognized by the Sca-1 antibody has been found on murine hematopoietic stem cells and some hematopoietic precursors, T lymphocytes, and nonhematopoietic cell lineages, suggesting a complex array of gene regulatory elements. The ability to use the Ly6E.1/A.2 transcriptional regulatory elements to direct expression of heterologous genes will allow for the manipulation of these cells during development and in hematopoietic cell transplantations. To identify the elements necessary for high-level expression, we have made deletion constructs of Ly-6E.1 gene flanking regions containing DNase I hypersensitive sites, tested them for expression in hematopoietic cells, and have performed kinetic analyses to correlate the appearance of hypersensitive sites with gene transcription and protein expression. We show that a 3' region containing two DNase I hypersensitive sites at +8.7 and +8.9 kb is required for high-level, gamma-interferon (gamma-IFN)-induced expression of the Ly-6E.1 gene and that a consensus sequence for a gamma-IFN-responsive element localizes to the +8.7 site. We also provide a description of allele- and cell-specific DNase I hypersensitive site patterns of the Ly-6E.1 and Ly-6A.2 genes. Taken together, these data indicate that while both 5' and 3' hypersensitive sites are rapidly induced with gamma-IFN, the 3' most distal hypersensitive sites are involved in directing high levels of expression of Sca-1 in hematopoietic cells.

Animals↗
PubMed1996

Remedies for common family ailments: 10. Nasal decongestants.

Nasal congestion and sinusitis are common effects of cold and flu viruses. One treatment for nasal congestion is oral doses of vasoconstrictors such as ephedrine which mimic the action of the sympathetic nervous system. Care should be taken before these are prescribed or recommended as these drugs are contraindicated in patients on certain drugs or with certain conditions. Vasoconstrictors can also be given as nasal drops or sprays but for a limited period to avoid rebound congestion. Aromatic volatile oils, e.g. menthol, eucalyptus, can be given as rubs or inhalants (see manufacturers' instructions for use with young children).

Common Cold↗
PubMed1996

Remedies for common family ailments: 11. Relieving the pain of sports injuries.

Many sports injuries involve tissue damage which results in the release of chemical mediators such as prostaglandin. These stimulate the nerve endings, producing pain. Many topical analgesics, eg aspirin and NSAIDs, act by inhibiting these chemical mediators. Others work on the "counter-irritant" principle, or by producing local heat or cold. Anyone on other medication or with existing medical conditions should consult a pharmacist or doctor before embarking on analgesics.

Adult↗
PubMed1995

The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus.

B lymphocytes in the peripheral circulation are maintained in a non-proliferative state. Antigen recognition stimulates limited proliferation, whereas infection with Epstein-Barr virus (EBV) results in continual proliferation and the outgrowth of immortal cell lines. Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested, we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells. We show that the expression of four cell genes, cdc-2, cyclin E, CD23, and cyclin D2, are up-regulated approximately 100-fold as a result of EBV-mediated immortalization. Because these genes play a positive role in cell proliferation, we suggest that this regulatory switch contributes to controlling entry into the cell cycle. Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40, anti-IgM, and IL4, or EBV results in the rapid expression of the same four genes, suggesting that, after infection, EBV exploits the normal program of B-lymphocyte cell cycle activation.

Adult↗
PubMed1995

Epstein-Barr virus efficiently immortalizes human B cells without neutralizing the function of p53.

Epstein-Barr virus (EBV) efficiently converts resting human B cells into actively cycling, immortal, lymphoblastoid cell lines (LCLs). Here we show that LCLs expressing the full complement of latent viral genes are very sensitive to DNA-damaging agents such as cisplatin. The response includes a rapid accumulation of the tumour suppressor protein p53 and induction of the cellular genes mdm2 and WAF1/p21. Although the levels of Bcl2 protein and Bax mRNA appear unaltered by the activation of p53, within 24 h the majority of cells undergo apoptosis. Over-expression of wild-type p53 in an LCL also resulted in apoptosis; this was preceded by the dephosphorylation of the retinoblastoma gene product, pRb. Primary resting B cells showed no response to cisplatin and even after drug treatment, p53 remained undetectable. However, after infection with EBV, p53 gene expression was induced to a similar level to that found in mitogen-activated B cells. When the physiologically activated primary B cells were exposed to cisplatin, although p53 accumulated as in LCLs, the outcome was growth-arrest rather than gross cell death. We conclude that, in contrast to the transformation of fibroblasts by adenovirus, SV40 or HPV, when B cells become activated and immortalized by EBV they are sensitized to the p53-mediated damage response. When the resulting LCLs are treated with genotoxic agents such as cisplatin, they are unable to arrest like normal cells because they are driven to proliferate by EBV and consequently undergo apoptosis.

Apoptosis↗
PubMed1995

Anti-p57: a novel association with neonatal lupus.

IgG antibodies to a 57-kD protein (p57) present in various human and bovine extracts were detected by immunoblotting in the serum of the mother of a baby with congenital heart block, but not in the corresponding cord blood, suggesting specific antibody consumption in the baby. Since this indicates a possible functional role for these antibodies, the antigen target was characterized and the association of the antibodies to heart block was further studied. A human K562 lambda gt11 cDNA library was screened and two clones were identified whose products reacted with the prototype serum. Antibody affinity-purified by use of the cloned gene products reacted on immunoblot with the 57-kD band. Partial sequences of both inserts were identical, but differed from DNA encoding the Ro(SSA) and La(SSB) antigens. Antibodies to the p57 were detected in 10% of systemic lupus erythematosus (SLE) sera, almost exclusively in association with anti-Ro(SSA). Furthermore, they were present in 38% (8/21) mothers of babies with neonatal lupus expressing either cardiac or cutaneous manifestations. Antibodies to this 57-kD protein may be an additional risk factor for neonatal lupus in anti-Ro-positive women. Moreover, disappearance of antibody from cord blood suggests that they may have a role in disease manifestations.

Autoantibodies↗
PubMed1995

A baboon (Papio hamadryas) model of insulin-dependent diabetes.

Over a period of four years, streptozocin has been used to induce diabetes in 10 baboons, all of whom are insulin dependent. We describe our experience with their husbandry, induction of diabetes, insulin therapy, metabolic control and growth rate. Streptozocin dosage of 60 mg/kg readily induces hyperglycemia with minimal hepatic or renal toxicity. Using a once daily injection of mixed short and intermediate acting insulins at a dosage of 2-4 U/kg, it is possible to maintain a degree of metabolic control similar to that attained in patients.

Aging↗