Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.     

Possible anatomical base of snoring

Variations of the medial and inferior choanal limits may facilitate snoring. These are: 1) short vomer without crista choanalis vomeris and adaptational formations, 2) extremely concave posterior margin of the hard palate leading to disproportion between the muscular and aponeurotic part of m. tensor veli palatini and hence to a flabby soft palate especially during sleep, and 3) neonatal relation of the height and width of the choane resulting in a very large choanal region instead of relative reduction of choanal width compared to its increasing height. All these variations result in a flabby soft palate especially during sleep and may lead to formation of whirles of inspired air and snoring.     

Development of an auxotrophic oral live Shigella flexneri vaccine

An oral live attenuated Shigella flexneri vaccine candidate strain was constructed by making it auxotrophic and dependent on aromatic metabolites not available in mammalian tissues. An aroD gene of Escherichia coli K12 strain NK 5131, inactivated by insertion in it of the Tn 10 transposon, was transduced using phage P1 into a virulent S. flexneri serotype Y strain (Sfl 1) isolated from a patient with bacillary dysentery. One of the transductant strains Sfl 114 was found to invade HeLa cells in vitro, to cause plaque formation in HeLa monolayers (i.e. maintain intracellular multiplication in vitro), but to be unable to cause keratoconjunctivitis in guinea-pig eyes. When the strain was fed to Macacca fascicularis monkeys it was well tolerated, excreted for 1-4 days, and found to elicit a local intestinal sIgA and serum IgA, IgM and IgG responses. Monkeys challenged with 100 ID50 dose (1 X 10(11) bacteria) of the virulent parent Sfl 1 strain were completely protected from development of diarrhoea. Coloscopy of the monkeys and the sampling of intestinal biopsies showed that the vaccine protected against the surface epithelial erosions and ulcerations seen in unimmunized monkeys. Killing of invading virulent shigellae apparently took place intracellularly in the mucosa suggesting that cellular immune mechanisms played a role in the elicited host defence. The constructed S. flexneri Sfl 114 strain has the properties of a promising shigella vaccine and will next be the subject of studies with human volunteers.     

Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Linseed and cod liver oil induce rapid growth in a 7-year-old girl with N-3- fatty acid deficiency

N-3 fatty acid deficiency is described in a 7-year-old girl who had been fed solely by gastric tube from the age of 3 years. She had received the same nutrient during the last 22 months, supplying 16.2% of calories from linoleate and 0.07% from alpha-linolenate. She weighed 9.5 kg at the age of 3, and 10.3 kg at the start of the study, the weight being constant the last 15 months. She was now supplemented daily with 1.2 ml of a linseed- and cod liver-oil mixture (5:1, v/v), thereby increasing her alpha-linolenate intake to 0.71% and total N-3 fatty acids to 0.74% of total energy. Two months later, her rate of weight gain was 0.43 kg/month. After 5 months, the fatty acid supplement was changed to 7.5 ml of cod liver oil daily, thereby changing alpha-linolenate and total N-3 acid intake to 0.10% and 1.3% of total energy, respectively. Her rate of weight gain now increased to 0.64 kg/month, and her length increased from 117 to 122 cm in 5 months. The results indicate that the optimal dietary requirement for N-3 fatty acids in this child is higher than 0.74%, and extrapolation estimated the optimal requirement to be 1.1%-1.2% of total calories. The results suggest that N-3 fatty acids are required for normal growth in man.     

Relation between energy expenditure and body composition in man: specific energy expenditure in vivo of fat and fat-free tissue

The relationship between energy expenditure and body composition, in terms of fat and fat-free masses, has previously been described by a variety of predictive regression equations with parameters devoid of physiological content. We present here results obtained by calculating the specific energy expenditure, ie, the energy expenditure per unit of mass, of fat and fat-free tissue on the basis of measurements of the total energy expenditure (EE), the masses of fat (FM), and fat-free (FFM) tissue using the following simple model: EE = k1.FM + k2.FFM where k1 and k2 are the specific energy expenditures of fat and fat-free tissue, respectively. The results of observations on 104 women at rest yielded values for k1 and k2 of 0.31 and 1.35 watts/kg of fat and fat-free mass, respectively, with standard errors of estimate of 0.074 and 0.052 watts/kg, respectively. Analysis of several series of measurements, from other sources and on smaller samples of subjects, yielded similar values at rest but with larger standard errors of estimate. Data from subjects performing varying amounts of work in 24-h measurements showed, as expected, larger values for both tissues. The results explain to a very large extent the well-established relation between resting metabolic rate and body weight, ie, a linear relation with a non-zero intercept. The results also offer a clear-cut explanation for the well known difference in energy expenditure between men and women with the same body weight.     

棕榈油对成人血脂和血小板功能的影响

报道了棕榈油（ＰＡ），花生油（ＰＥ）对血清总胆固醇水平（ＴＣ）在５．５～７．０ｍｍｏｌ／Ｌ的受试者血脂和血小板功能的影响。５１名受试者（男３１人，女２０人，年龄３０～６６岁之间）分为两组，一组男１５人，女１１人，称ＰＥ组；另一组男１６人女９人，称ＰＡ组，预备期３周，膳食以当地日常食用的花生油烹调，实验期６周。ＰＡ组受试者食用以棕榈油烹调的实验膳；ＰＥ组受试者仍食花生油烹调的膳食。脂肪约占膳食能量的３０％，其中６０％～６５％来自实验油。实验结果表明：与起始值相比，６周末ＰＡ组受试者血清ＴＣ，低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）和总胆固醇与高密度脂蛋白胆固醇比值（ＴＣ／ＨＤＬ－Ｃ）显著下降，血浆血栓素Ｂ２（ＴＸＢ２）／６－酮前列环素Ｆ１α、（６－ｋｅｔｏ－ＰＧＦ１α）比值显著下降，全血血小板聚集率未见显著变化。ＰＥ组受试者的血脂、血浆ＴＸＢ２、６－ｋｅｔｏ－ＰＧＦ１α及全血血小板聚集率等指标均未出现显著变化。提示，棕榈油作为我国居民家庭烹调用油并不会增加发生心血管疾病的危险。