PubMed Health⌕ Search

Biomedical subjects

H Bush

Publications and source records attributed to H Bush.

At least 19 recordsLinked to original sources

Evolution of atherogenic diets in South Asian and Italian women after migration to a higher risk region.

BACKGROUND: To identify differences in the evolution of the diets of South Asian and Italian migrants, a cross-sectional, multiethnic study was undertaken in Glasgow, Scotland. METHODS: Five groups of women aged 20-42 years comprising general population (n = 35), South Asian migrants (n = 35) British-born controls (n = 37), Italian migrants (n = 30) and British-born (n = 38) participated in an interviewer administered structured questionnaire on issues relating to health, diet and food selection. Anthropometric measurements were made and subjects completed a 7-day weighed diet inventory. RESULTS: Compared with the general population, dietary differences were greatest amongst first generation migrant groups. There were major differences between the two migrant groups. South Asian migrants tended to display a more atherogenic profile (fat 42.4% energy, saturated fat 15.0% energy, vitamin C 5.1 mg per 1000 kJ) than the general population (fat 39.1% energy, saturated fat 13.5% energy, vitamin C 6.8 mg per 1000 kJ), and Italian migrants (fat 35.7% energy, saturated fat 12.1% energy, vitamin C 10.9 mg per 1000 kJ). However, South Asian groups had higher intakes of polyunsaturated fatty acids which may be cardioprotective. CONCLUSIONS: South Asian migrants to Scotland appear to develop adverse dietary elements in the first generation, which are modified in subsequent generations, whereas Italians' diets remain cardioprotective in the migrant generation but deteriorate in subsequent generations.

Acculturation↗

A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation.

Both the risk and the rate of development of atherosclerosis are increased in diabetics, but the mechanisms involved are unknown. Here we report a glucose-mediated increase in CD36 mRNA translation efficiency that results in increased expression of the macrophage scavenger receptor CD36. Expression of CD36 was increased in endarterectomy lesions from patients with a history of hyperglycemia. Macrophages that were differentiated from human peripheral blood monocytes in the presence of high glucose concentrations showed increased expression of cell-surface CD36 secondary to an increase in translational efficiency of CD36 mRNA. We obtained similar data from primary cells isolated from human vascular lesions, and we found that glucose sensitivity is a function of ribosomal reinitiation following translation of an upstream open reading frame (uORF). Increased translation of macrophage CD36 transcript under high glucose conditions provides a mechanism for accelerated atherosclerosis in diabetics.

5' Untranslated Regions↗

Ethnic differences in anthropometric and lifestyle measures related to coronary heart disease risk between South Asian, Italian and general-population British women living in the west of Scotland.

AIMS: To compare anthropometric measurements and to define their behavioural associations in migrant and British-born South Asians (who have increased cardiovascular risk) or Italians (who have reduced cardiovascular risk), and in the general population of British women living in the west of Scotland. STUDY DESIGN: Cross-sectional survey of women aged 20-42 y, selected mainly from birth registration data, which included 63 migrant South Asians, 56 British-born South Asians, 39 migrant Italians, 51 British-born Italians, and 50 subjects representative of the general population of women, all resident in the west of Scotland. MEASUREMENTS: Height, weight, body mass index (BMI), and waist and hip circumferences. RESULTS: With age adjustment, migrant South Asians (0.88) had greater waist-to-hip ratio than British-born South Asians (0.84; P<0.05), while there was no difference between migrant (0.81) and British-born (0.79) Italian groups. Both migrant (P<0.001) and British-born South Asian (P<0.05) groups had higher waist-to-hip ratio and were about 3 cm shorter than Italian groups and the general population. Neither weight nor BMI were different between ethnic groups. Waist and hip circumferences were not different between migrant and British-born ethnic minority groups. Migrant South Asians (86.8 cm) had significantly (P<0.05) larger waist circumference than the general population (78.6 cm). British-born Italian women (103.0 cm) had larger hip circumference than the general population of women (96.4 cm), while other groups had similar hip circumferences. Additional adjustments for physical activity, smoking, alcohol consumption and parity reduced the differences in anthropometric measurements: only waist-to-hip ratio of migrant South Asians remained significantly (P<0.01) higher than that of the general population women. CONCLUSIONS: The adverse anthropometric indicators of cardiovascular risk in migrant South Asian women are substantially explained by their lifestyle factors and parity. British-born South Asian women are more similar to the general population women. Anthropometric differences between migrant or British-born Italians and the general population women are small.

Adult↗

Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-beta type II receptor.

Atherosclerotic lesions may progress due to a "failure to die" by vascular repair cells. Egr-1, a zinc finger transcription factor, is elevated more than 5-fold in human carotid lesions relative to the adjacent tunica media. Lesion cells in vitro also express 2-3-fold higher Egr-1 mRNA and protein levels but express much lower levels of the transforming growth factor-beta (TGF-beta) Type II receptor (TbetaR-2) and are functionally resistant to the antiproliferative effects of TGF-beta. Lesion cells fail to express a TbetaR-2 promoter/chloramphenicol acetyltransferase (CAT) construct but overexpress an Egr-1-inducible platelet-derived growth factor-A promoter/CAT construct. Transfection of Egr-1 cDNA represses TbetaR-2/CAT constructs but induces PDGF-A/CAT. Egr-1 transfection reduces the levels of TbetaR-2 and confers resistance to the antiproliferative effect of TGF-beta1. Egr-1 can interact directly with both the -143 Sp1 site and the positive regulatory element 2 (PRE2) (ERT/ets) region of the TbetaR-2 promoter. Thus, although activating a family of stress-responsive genes, Egr-1 also transcriptionally represses one of the major inhibitory pathways that restrains vascular repair.

Arteries↗

High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis.

To understand the mRNA transcript profile in the human atherosclerotic lesion, RNA was prepared from the fibrous cap versus adjacent media of 13 patients undergoing carotid endarterectomy. cDNA expression arrays bearing 588 known genes indicated that lesions express unexpectedly high levels of the early growth response gene, Egr-1 (NGFI-A), a zinc-finger transcription factor that modulates a cluster of stress-responsive genes including PDGF and TGF-beta. Expression of Egr-1 was an average of 5-fold higher in the lesion than in the adjacent media, a result confirmed by RT-PCR, and many Egr-1-inducible genes were also strongly elevated in the lesion. Time-course analyses revealed that Egr-1 was not induced ex vivo. Immunocytochemistry indicated that Egr-1 was expressed prominently in the smooth muscle-actin positive cells, particularly in areas of macrophage infiltration, and in other cell types, including endothelial cells. Induction of atherosclerosis in LDL receptor-null mice by feeding them a high-fat diet resulted in a progressive increase in Egr-1 expression in the aorta. Thus, induction of Egr-1 by atherogenic factors may be a key step in coordinating the cellular events that result in vascular lesions.

Animals↗

Preparative resolution of enantiomers of prostaglandin precursors by liquid chromatography on a chiral stationary phase.

Preparative liquid chromatographic methods were developed for the chiral resolution of two different cyclopentenone precursors of a synthetic prostaglandin. Various solvent combinations of alcohols and alkanes were investigated to determine the method which has the greatest throughput. The effect of particle size on the chiral resolution was also investigated. In addition, the preparative system was automated to allow for unattended operation for up to 10 h.

Chemical Phenomena↗

Heroin vs morphine for cancer pain?

Narcotic analgesics are the mainstay of pain control in patients with cancer. A controversy has been raging in the United States and Canada as to the legalization of heroin. We have reviewed the literature in order to determine the relative efficacy of heroin and morphine in cancer pain. We applied the following methodologic criteria: Was the assignment of patients to the different opiates randomized? Were all clinically relevant outcomes reported? Were the patients recognizable? Were both clinical and statistical significance considered? Was the opiate regimen feasible in routine clinical practice? Were all patients who entered the study accounted for at its conclusion? Two trials satisfied our first standard. The first, a double-blind cross-over trial, failed to meet standard 4 (the negative conclusion may represent a type 2 error) and only 21% of patients completed both treatment periods. The second study, which compared intramuscular heroin and morphine among patients with postoperative pain, failed to meet standards 3 (patients not described in sufficient detail and only tangentially related to chronic cancer pain) and 4 (type 2 error). Thus the relative efficacy of heroin and morphine in the relief of chronic cancer pain remains unknown. Randomized trials that meet all six methodologic standards must therefore be carried out for this controversy to be resolved.

Clinical Trials as Topic↗

Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer.

327 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after total mastectomy and axillary clearance, to receive either no additional treatment or oral cyclophosphamide 80 mg/m2 on days 1-14, intravenous methotrexate 32 mg/m2 on days 1 and 8, and intravenous fluorouracil 480 mg/m2 on days 1 and 8 (CMF), which was repeated every 28 days for twelve cycles. There was a significantly longer relapse-free survival (RFS) in patients treated with CMF. A prolonged RFS was seen in premenopausal patients, those with 1-3 nodes involved, and those with 4 or more nodes involved, but a similar trend in postmenopausal patients failed to reach statistical significance. RFS was greater in patients with CMF-induced amenorrhoea than in controls and in treated patients whose primary tumour contained progesterone receptors. Dose of chemotherapy did not have a significant effect on RFS. Survival was not influenced by treatment.

Adult↗

Controlled trial of adjuvant chemotherapy with melphalan for breast cancer.

370 patients who had carcinoma of the breast with involved axillary lymph-nodes were randomised after total mastectomy and axillary clearance to receive either no additional treatment or melphalan 6 mg/m2 daily for 5 days every 6 weeks for sixteen cycles. There was a trend towards longer relapse-free survival (RFS) in patients treated with melphalan, but this was not significant either in the whole series or in sub-groups according to menopausal status or extent of nodal involvement. In patients receiving melphalan RFS was not significantly affected by either the occurrence of amenorrhoea or the dosage of melphalan received. Overall survival did not differ significantly between the two groups. The results of this trial suggest that there is no place for the use of melphalan as adjuvant therapy in the management of early breast cancer.

Adult↗

A comparison of ticlopidine and heparin on hemodialysis in dogs.

The efficacies of low-dose heparin and low-dose heparin plus ticlopidine as anticoagulants during hemodialysis in acutely uremic dogs were compared and evaluated. Heparin was administered as a bolus at a dose of 100 U/kg. In preliminary experiments it was determined that dogs dialyzed with ticlopidine alone demonstrated gross clotting of the artificial kidney within 2.5 hr. Ticlopidine was administered by gavage at a dose of 50 mg/kg/day starting 72 hr prior to hemodialysis and continuing throughout the period of hemodialysis (4 days). Each dog was dialyzed four times with either heparin alone or heparin plus ticlopidine. Each hemodialysis lasted 3.5 hr. Parameters followed included dialysis clearance of urea and creatinine, ultrafiltration rate, residual blood volume, gross clotting episodes, platelet count, and levels of fibrinogen and thromboxane B2. A lesser degree of hemodialysis-associated thrombocytopenia, a lower residual blood volume, fewer episodes of gross clotting, no reduction in fibrinogen levels, and no increase in thromboxane B2 levels were observed in the heparin plus ticlopidine group as compared to the heparin group alone. Although ticlopidine at the dosage employed should not be used as the sole anticoagulant for hemodialysis, it may be useful when added to low-dose heparin. The salutary effects demonstrated in this study suggest clinical benefits of the combination.

Animals↗

A comparison of prostacyclin and heparin on hemodialyses in dogs.

A comparison of the efficacy of prostacyclin and heparin as anticoagulants during hemodialysis in uremic dogs was evaluated. Prostacyclin was infused continuously into the arterial limb of the dialyzer (100 ng/kg/min) while heparin was administered as a 5000 unit bolus at the beginning of dialysis. Prostacyclin and heparin were alternated and a total of 4 dialyses/dog were performed. Parameters followed to assess the efficacy of dialyses included: dialysance (ml/min) of urea, creatinine, ultrafiltration rate (ml/hr), residual volume and platelet count (% of baseline). A lesser degree of hemodialysis associated thrombocytopenia, and a higher ultrafiltration rate were observed with prostacyclin. These studies demonstrate that prostacyclin can be used alone as an anticoagulant in a uremic dog model, and in contrast to heparin it maintains the platelet count and improves the ultrafiltration rate during hemodialysis.

Animals↗

Serum glycoprotein hormone alpha subunit, hormone receptors and disease stage in patients with breast cancer.

The concentration of the common alpha subunit of the glycoprotein hormones was high in the serum of 21/56 (38%) of premenopausal patients and 22/106 (21%) of postmenopausal patients with primary breast cancer, at the time of presentation. 7/59 (12%) of patients with benign disease also had high alpha subunit levels. Tumour cytosol oestrogen and progesterone receptor status was determined in 80% of the patients with cancer, and there was a trend towards higher alpha levels in patients without receptors, but this was not statistically significant. In the premenopausal patients with cancer there was a significant correlation between alpha subunit level and disease stage, R = 0.47, P = 0.0001, but not in the postmenopausal patients. In view of the correlation with disease stage, high levels of alpha subunit in premenopausal patients with breast cancer at presentation with the primary tumour may indicate poor prognosis.

Adult↗