Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies.

OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.     

The growth of compact and diffuse variants of Staphylococcus aureus in bovine mastitic and normal whey

Strains of Staphylococcus aureus producing either diffuse or compact colonies in serum-soft agar were grown in bovine normal and mastitic whey. Bacterial growth was followed by automated turbidometry. Compact strains multiplied faster and to higher final numbers in mastitic whey than diffuse strains, whereas diffuse strains grew to higher numbers in normal whey. Nutrients (hemolysed bovine blood, bovine serum, proteose-peptone) were added to normal whey to enhance bacterial growth as in mastitic whey. The growth-promoting effect of these nutrients was dose-dependent for compact strains but not for diffuse strains. The difference in the growth characteristics of diffuse and compact strains in bovine whey explains some aspects of the pathogenesis of bovine mastitis.     

A, B, D cells and a fourth cell type in long-term cultures of fetal rat pancreas.

Whole pancreases from fetal rats of 13 days and 18 days gestation were explanted onto rayon grids and grown in organ culture. Cultures were fixed in Bouin's fluid, sectioned and stained with the fluorescent antibody techniques for glucagon and insulin, aldehyde fuchsin for B cells, pseudoisocyanin for D cells and a silver technique for the fourth cell type. The 13-day explants were fixed after 10 days in culture. A, B and D and the fourth cell type were seen, indicating that precursors of all four endocrine cell types must be present in the fetal pancreas shortly after the formation of the pancreatic bud (11 days). Further, the presence of these four cell types in the walls of tubules in these cultures indicates the tubules as the site of origin of all the endocrine tissue. The 18-day explants were collected every other day of culture from 2 to 30 days in a long-term experiment. A number of large islets with well granulated B cells was still present after 30 days of culture. The relative abundance of cell types at different stages was estimated as follows: 18-day fetal controls, A greater than B=4 greater than D; after 2 to 10 days in culture, B greater than A greater than or equal to D; after 18 to 30 days in culture, B greater than D greater than A greater than 4.     

The effects of agents modifying sympathetic nerve function on the response of the isolated rat tail artery to etilefrine and tyramine.

The effects of etilefrine on the ventral caudal artery of the rat have been examined in the presence of agents modifying sympathetic nerve function. Catecholamine levels were also measured in adjacent segments of artery to those studied pharmacologically and an attempt made to relate vascular response to etilefrine (and tyramine) with catecholamine content. Both guanethidine and reserpine produced significant attenuation of the vascular effects of etilefrine and tyramine. Pre-treatment with a monoamine oxidase inhibitor caused an increase in tissue catecholamine levels but, paradoxically, depressed the vascular response to etilefrine. The significance of some of the findings in terms of an indirect component to etilefrine's action are discussed.     

Rho GTPase–independent regulation of mitotic progression by the RhoGEF Net1

Neuroepithelial transforming gene 1 (Net1) is a RhoA-subfamily–specific guanine nucleotide exchange factor that is overexpressed in multiple human cancers and is required for proliferation. Molecular mechanisms underlying its role in cell proliferation are unknown. Here we show that overexpression or knockdown of Net1 causes mitotic defects. Net1 is required for chromosome congression during metaphase and generation of stable kinetochore microtubule attachments. Accordingly, inhibition of Net1 expression results in spindle assembly checkpoint activation. The ability of Net1 to control mitosis is independent of RhoA or RhoB activation, as knockdown of either GTPase does not phenocopy effects of Net1 knockdown on nuclear morphology, and effects of Net1 knockdown are effectively rescued by expression of catalytically inactive Net1. We also observe that Net1 expression is required for centrosomal activation of p21-activated kinase and its downstream kinase Aurora A, which are critical regulators of centrosome maturation and spindle assembly. These results identify Net1 as a novel regulator of mitosis and indicate that altered expression of Net1, as occurs in human cancers, may adversely affect genomic stability.     

Vascular effects of etilefrine. Further studies to substantiate the predominant indirect sympathomimetic action of this agent.

The suggested use of etilefrine in the treatment of patients with orthostatic hypotension is based on the premise that it has an action similar to that of noradrenaline (Miller, Wiener and Bloomfield, 1973). However, earlier work from this laboratory (Frost, Frewin and Gerke, 1977; Frost, Frewin, Gerke and Downey, 1978; Frost, Halloran, Frewin, Gerke and Downey, 1978) on blood vessels in the rat tail has suggested that the drug acts predominantly as an indirect sympathomimetic agent. The present study examined the action of etilefrine on the central artery of the rabbit ear. This vessel is known to have a rich sympathetic innervation (de la Lande, Frewin and Waterson, 1967) and has the added advantage that it can be surgically denervated. It therefore became possible to examine the effects of etilefrine on both normal and denervated arteries and to quantitate the extent to which the drug relied on the symphathetic nerves for its vasoconstrictor effects.