Early growth and death from cardiovascular disease in women.

OBJECTIVE--To determine whether the link suggested between growth in utero and during infancy and death from cardiovascular disease in men is also present in women. DESIGN--Follow up study of women and men whose birth weight and weight at 1 year of age had been recorded. SETTING--Hertfordshire, England. SUBJECTS--5585 women and 10,141 men born during 1911-30. MAIN OUTCOME MEASURES--Standardised mortality ratios for cardiovascular disease. RESULTS--Among women and men death rates from cardiovascular disease fell progressively between the low and high birth weights groups (chi 2 = 4.3, p = 0.04 for women, chi 2 = 8.5, p < 0.005 for men). Cardiovascular deaths in men but not women were also strongly related to weight at 1 year, falling progressively between the low and high weight groups (chi 2 = 27.5, p < 0.0001). The highest cardiovascular death rates in women were among those with below average birth weight but above average weight at 1 year. In men the highest rates were among those with below average birth weight and below average weight at 1 year. CONCLUSION--Relations between cardiovascular disease and birth weight are similar in men and women. In men cardiovascular disease is also related to weight gain in infancy.     

Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life.

OBJECTIVE--To determine whether reduced fetal and infant growth are associated with higher plasma fibrinogen and factor VII concentrations in adult life. DESIGN--Follow up study of men born during 1920-30 whose weights at birth and at 1 year had been recorded by health visitors, and men born during 1935-43 whose size at birth had been measured in detail. SETTING--Hertfordshire and Preston, England. SUBJECTS--591 men born in east Hertfordshire who still lived there and 148 men born in Preston who still lived in or close to the city. MAIN OUTCOME MEASURES--Plasma fibrinogen and factor VII concentrations. RESULTS--Among men in Hertfordshire mean plasma fibrinogen and factor VII concentrations fell with increasing weight at 1 year (from 3.21 g/l in men of less than or equal to 18 lb to 2.93 g/l in men greater than or equal to 27 lb and from 122% of standard to 103%; p less than 0.001, p less than 0.005 respectively). The trends were independent of cigarette smoking, alcohol consumption, body mass index, and social class. Neither plasma fibrinogen nor factor VII concentration was related to birth weight. In men in Preston, however, fibrinogen concentration fell progressively as the ratio of placental weight to birth weight decreased (p = 0.01). CONCLUSIONS--Reduced growth in fetal life and infancy is strongly related to high plasma concentrations of the haemostatic factors fibrinogen and factor VII. This may be a persisting response to impaired liver development during a critical early period.     

Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease.

OBJECTIVE--To examine whether method of infant feeding is associated with adult serum lipid concentrations and mortality from ischaemic heart disease. DESIGN--Follow up study of men born during 1911-30. SETTING--Hertfordshire, England. SUBJECTS--5718 men, for 5471 of whom information on infant feeding had been recorded by health visitors and 1314 of whom had died. 485 of the men born during 1920-30 and still living in Hertfordshire who had blood lipid measurements. MAIN OUTCOME MEASURES--Death from ischaemic heart disease; serum cholesterol and apolipoprotein concentrations. RESULTS--474 men had died from ischaemic heart disease. Standardised mortality ratios were 97 (95% confidence interval 81 to 115) in men who had been breast fed and had not been weaned at 1 year, 79 (69 to 90) in breast fed men who had been weaned at 1 year, and 73 (59 to 89) in men who had been breast and bottle fed. Compared with men weaned before one year men not weaned had higher mean serum concentrations of total cholesterol (6.9 (not weaned) v 6.6 (weaned) mmol/l), low density lipoprotein cholesterol (5.0 v 4.6 mmol/l) and apolipoprotein B (1.14 v 1.08 g/l). Men who had been bottle fed also had a high standardised mortality ratio for ischaemic heart disease (95; 68 to 130) and high mean serum concentrations of total cholesterol (7.0 mmol/l), low density lipoprotein cholesterol (5.1 mmol/l), and apolipoprotein B (1.14 g/l). In all feeding groups serum apolipoprotein B concentrations were lower in men with higher birth weight and weight at 1 year. CONCLUSIONS--Age of weaning and method of infant feeding may influence adult serum low density lipoprotein cholesterol concentrations and mortality from ischaemic heart disease. Adult serum apolipoprotein B concentrations are related to growth in fetal life and infancy.     

The Caenorhabditis elegans spe‐49 gene is required for fertilization and encodes a sperm‐specific transmembrane protein homologous to SPE‐42

Fertilization, the fusion of sperm and oocyte to form a zygote, is the first and arguably the most important cell–cell interaction event in an organism’s life. Forward and reverse genetic approaches in the nematode Caenorhabditis elegans have identified many genes that are required for gametogenesis and fertilization and thus are beginning to elucidate the molecular pathways that underlie these processes. We identified an allele of the spe‐49 gene in a second filial generation (F₂) mutagenesis screen for spermatogenesis‐defective (spe) mutants. Mutant worms for spe‐49 produce sperm that have normal morphology, activate to form ameboid spermatozoa, and can migrate to and maintain their position in the hermaphrodite reproductive tract but fail to fertilize oocytes. This phenotype puts spe‐49 in the spe‐9 class of late‐acting genes that function in sperm at the time of fertilization. We cloned the spe‐49 gene through a combination of deficiency mapping, transgenic rescue, and genomic sequencing. spe‐49 messenger RNA (mRNA) is enriched in male germ cells, and the complementary DNA (cDNA) encodes a predicted 772‐amino‐acid six‐pass transmembrane protein that is homologous to SPE‐42. Indeed, SPE‐49 and SPE‐42 have identical predicted membrane topology and domain structure, including a large extracellular domain with six conserved cysteine residues, a DC‐STAMP domain, and a C‐terminal cytoplasmic domain containing a C4–C4 RING finger motif. The presence of two SPE‐42 homologs in animal genomes from worms to humans suggests that these proteins are highly conserved components of the molecular apparatus required for the sperm–oocyte recognition, binding, and fusion.     

Evidence for glutathione peroxidase activities in cultured plant cells

Extracts from cultured plant cells of spinach, maize and sycamore and from Lemna plants contain detectable glutathione peroxidase activity, using either hydrogen peroxide or t-butyl hydroperoxide as substrates. Using extracts from cultured maize cells, two peaks of glutathione peroxidase activity could be resolved by a combination of gel filtration and ion exchange chromatography. One peak was eluted along with glutathione transferase activity; the second was distinct from both glutathione transferase and ascorbic acid peroxidase, and was active with both hydrogen peroxide and organic hydroperoxides. It seems likely that at least two enzymes with glutathione peroxidase activity exist in higher plant cells.     

Enzymatic methylation of sulfide, selenide, and organic thiols by Tetrahymena thermophila

Cell extracts from the ciliate Tetrahymena thermophila catalyzed the S-adenosylmethionine-dependent methylation of sulfide. The product of the reaction, methanethiol, was detected by a radiometric assay and by a gas-chromatographic assay coupled to a sulfur-selective chemiluminescence detector. Extracts also catalyzed the methylation of selenide, and the product was shown by gas chromatography-mass spectrometry to be methaneselenol. The sulfide and selenide methyltransferase activities copurified with the aromatic thiol methyltransferase previously characterized from this organism (A.-M. Drotar and R. Fall, Pestic. Biochem. Physiol. 25:396-406, 1986), but heat inactivation experiments suggested the involvement of distinct sulfide and selenide methyltransferases. Short-term toxicity tests were carried out for sulfide, selenide, and their methylated derivatives; the monomethylated forms were somewhat more toxic than the nonmethylated or dimethylated compounds. Cell suspensions of T. thermophila exposed to sulfide, methanethiol, or their selenium analogs emitted methylated derivatives into the headspace. These results suggest that this freshwater protozoan is capable of the stepwise methylation of sulfide and selenide, leading to the release of volatile methylated sulfur or selenium gases.     

Enzymatic synthesis of isoprene from dimethylallyl diphosphate in aspen leaf extracts

Aspen (Populus tremuloides Michx.) leaf extracts contain a newly discovered enzyme activity that catalyzes the magnesium ion-dependent elimination of diphosphate from dimethylallyl diphosphate with rearrangement to form isoprene (2-methyl, 1-3-butadiene). This isoprene synthase activity has been partially purified. The nonenzymatic reaction of dimethylallyl diphosphate to isoprene, known to be acid catalyzed, may be insignificant at physiological pH. In contrast, the enzymatic reaction may be responsible for the majority of light-dependent isoprene production by isoprene-emitting plants.     

Enzymatic methylation of sulfide, selenide, and organic thiols by Tetrahymena thermophila.

Cell extracts from the ciliate Tetrahymena thermophila catalyzed the S-adenosylmethionine-dependent methylation of sulfide. The product of the reaction, methanethiol, was detected by a radiometric assay and by a gas-chromatographic assay coupled to a sulfur-selective chemiluminescence detector. Extracts also catalyzed the methylation of selenide, and the product was shown by gas chromatography-mass spectrometry to be methaneselenol. The sulfide and selenide methyltransferase activities copurified with the aromatic thiol methyltransferase previously characterized from this organism (A.-M. Drotar and R. Fall, Pestic. Biochem. Physiol. 25:396-406, 1986), but heat inactivation experiments suggested the involvement of distinct sulfide and selenide methyltransferases. Short-term toxicity tests were carried out for sulfide, selenide, and their methylated derivatives; the monomethylated forms were somewhat more toxic than the nonmethylated or dimethylated compounds. Cell suspensions of T. thermophila exposed to sulfide, methanethiol, or their selenium analogs emitted methylated derivatives into the headspace. These results suggest that this freshwater protozoan is capable of the stepwise methylation of sulfide and selenide, leading to the release of volatile methylated sulfur or selenium gases.