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A targeted gold nanoparticle has been developed as a contrast agent for photoacoustic medical imaging. We have studied cancer cell targeting by antibody conjugated gold nanorods for high contrast photoacoustic imaging. By changing the aspect ratio of the elongated “rod” shape of the gold nanoparticle, its plasmon peak absorption wavelength can be tuned to the near IR (700–900 nm) for an increased penetration depth into biological tissue. Effective cell targeting and sensitive photoacoustic detection of a single layer of cells are demonstrated. Combining ultrasound with contrast agent based photoacoustic imaging is proposed as a visual tool to compound molecular and structural information for early stage prostate cancer detection. [ABSTRACT FROM AUTHOR]

Zinc and phytate intakes of 183 rural Gambian infants were obtained from weighed records of breastmilk and food intake and measured contents in foods. Total zinc intake of 2.7 mg/d in the first month of age declined to 1.5 mg/d at 3 months, then increased to 4.3 mg/d by 17 months. Breastmilk was an important source of zinc, but the predominant cereal and groundnut-based foods had high [phytate]/[Zn] molar ratios ranging from 13 to 28, indicating potential impaired zinc bioavailability. The [phytate]/[Zn] molar ratio for the diet as a whole was low in early infancy, but increased to 13 in the second year. In contrast, this ratio was less than 6 for the diet of 48 Cambridge breastfed infants up to 18 months. A further disadvantage to the Gambian infants was indicated by their lower intake of protein of animal origin. However, calcium intake was estimated in both communities to be below the level which could give rise to zinc chelation in association with phytate. Compared to 'basal' and 'normative' requirements, total zinc intake of the Gambian infants showed the greatest shortfall between 3 and 12 months, making this the age band for maximum probable benefit from focused intervention programmes. [ABSTRACT FROM AUTHOR]

Objectives: To attempt to identify the relationship of the key regulator molecules in paclitaxel-induced apoptosis using two metastatic cell lines: the human prostate carcinoma LNCaP line and the cervical carcinoma HeLa cell line., Methods: Both LNCaP and HeLa cells were continuously exposed to clinically achievable concentrations of paclitaxel and observed for activation of programmed cell death as measured by cytotoxic dose-response curves, poly(adenosine diphosphate-ribose) polymerase cleavage, bcl-2 phosphorylation, and the activation of caspase-7 (interleukin-1 beta converting enzyme (ICE)-LAP3)., Results: Initially, we asked whether paclitaxel-induced bcl-2 phosphorylation is triggered by the spindle assembly checkpoint via an active cdc2 kinase-dependent pathway and whether phosphorylation of endogenous bcl-2 is the signal that activates cell death machinery. Paclitaxel-induced G2/M cell cycle arrest correlated with cdc2 kinase activity and bcl-2 phosphorylation. Olomoucin, a specific inhibitor of cyclin-dependent kinases, inhibited bcl-2 phosphorylation. On the basis of these studies, we then investigated whether bcl-2 was phosphorylated in a cell cycle-dependent fashion. Analysis of synchronized HeLa cells demonstrated that endogenous bcl-2 is phosphorylated in a G2/M cell cycle-dependent manner without apoptosis., Conclusions: Our results indicate that the events associated with paclitaxel-induced cytotoxicity are connected to each other and represent the signaling network of paclitaxel-induced mitotic arrest and cell death. In addition, we confirmed that the death-decision of paclitaxel-induced apoptosis is not mediated by bcl-2 phosphorylation and believe that this decision may be mediated by the activated spindle assembly checkpoint.

The chemotherapeutic agent paclitaxel disrupts microtubule dynamics causing mitotic arrest, which leads to cell death. However, in paclitaxel-resistant tumor cells, treatment with paclitaxel induces abnormal progression through prophase resulting in a multimininucleated phenotype. Multimininucleation and subsequent polyploidization have been correlated with paclitaxel resistance. Paclitaxel treatment of HeLa cells resulted in cell death via typical activation of the apoptotic machinery, whereas treatment of the relative paclitaxel-resistant prostate cancer cell line PC-3 induced an attenuated caspase activation and multimininucleation. The multimininucleated phenotype could be mimicked in HeLa cells treated with paclitaxel and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), a peptide caspase inhibitor. Interestingly, we observed no discernible difference in the pattern of cdc-2 kinase activation or phosphorylation of bcl-2-like proteins in PC-3 and HeLa cells treated with paclitaxel, which demonstrated that these molecules could not be used as indicators for the degree of caspase activation. In this study, we establish a connection between relative paclitaxel resistance, caspase attenuation/inhibition, and the multimininucleated phenotype.

In a day-care setting, 33 girls and 34 boys, ranging in age from 36 to 73 months, responded to 30 tasks to obtain conventional measures of laterality and to determine their directional preferences on behaviors requiring whole body movement in a circle (circling) or pivoting about the body's vertical axis. Significant counterclockwise preferences were found for both kinds of turning behaviors, and there were no gender differences in these preferences. Increasing age was weakly associated with stronger right-handedness and counterclockwise preference on the circling tasks. These results are consistent with those of other studies and suggest that humans exhibit a small left-turning population preference in rotational movements.

Fluoride continues to be a safe and effective public health measure. In spite of a recent decline in caries reduction in the US due to the large number of supplemental fluorides available, water fluoridation remains a cost-effective method to prevent decay in children. Also, a review of the literature shows a lack of ill effects associated with fluoride use in children. Most recently, the United States Public Health Service continues to support fluoridation in terms of policy and research. In 1990, the US toxicology Program concluded there were no detrimental effects including cancer risk from fluoride use.

The Ca and P intakes of 148 pregnant and lactating women in a rural village in The Gambia, West Africa, have been estimated by direct weighing of food on a total of 4188 d. The Ca and P contents of local foods were determined by analysis of raw ingredients, snack foods and prepared dishes. Information about the contribution of mineral-rich seasonings was obtained. Efforts were made to discover unusual sources of Ca that might not be perceived as food by subject or observer. The main contributors to daily Ca intake were shown to be leaves, fish, cereals, groundnuts and local salt. Cow's milk accounted for only 5% of Ca intake. Unusual sources of Ca were discovered, namely baobab (Adansonia digitata) fruit and selected earths, but these were consumed infrequently and their contributions to Ca intakes were small. Cereals and groundnuts were the main sources of P. Ca and P intakes (mg/d) were shown to average 404 (SD 110) and 887 (SD 219) respectively. Seasonal changes in the availability of leaves, cereals and groundnuts resulted in variations in Ca and P intakes. The rainy season was associated with increased Ca intakes (by 16%) but decreased P consumption (by 15%). No difference was observed in Ca intake between pregnant and lactating women but P intake in lactation was 11% higher than that in pregnancy during the post-harvest season. The implications of these low Ca intakes require investigation.

Recombinant tissue factor pathway inhibitor (rTFPI) has been expressed in four mammalian expression systems using human SK hepatoma, mouse C127, baby hamster kidney (BHK), and Chinese hamster ovary (CHO) cells as hosts. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the immunoaffinity purified rTFPIs all show broad bands and the mean molecular weight of SK hepatoma and C127 rTFPIs (M(r) approximately 38,000) appear larger than those of BHK and CHO rTFPIs (M(r) approximately 35,000). All these proteins inhibit factor Xa and appear to bind factor Xa with 1:1 stoichiometry. The ability of these proteins to inhibit tissue factor-induced coagulation in plasma was examined using a prothrombin time assay. The relative activities of SK rTFPI:C127 rTFPI:BHK rTFPI:CHO rTFPI were found to be 28:15:2.1:1. By Western blot using specific antisera against the amino- and carboxy-termini of TFPI as probes, it is found that all the immunoaffinity purified rTFPIs possess approximately equal amounts of the amino terminus, but the C127 and BHK rTFPIs are deficient in carboxy terminus and the CHO rTFPI is essentially devoid of this region of the protein. Mono S chromatography allowed separation of the full-length and the truncated molecules with high and low anticoagulant activities, respectively. The above results suggest that proteolysis of the carboxy terminus of TFPI occurs to different extent when TFPI is expressed in different cells and that the carboxy terminal region of the TFPI molecule is important for the inhibition of tissue factor-induced coagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein-associated coagulation inhibitor produces feed-back inhibition of tissue factor (tissue thromboplastin)-induced coagulation in the presence of factor Xa Recombinant lipoprotein-associated coagulation inhibitor (rLACI) was tested for its ability to modify thromboplastin-induced intravascular coagulation in a rabbit model that allows monitoring of iodine-125 fibrin accumulation/disappearance in the lung and sampling of blood for the measurement of coagulation parameters. Infusion of thromboplastin into the rabbit caused a rapid increase of radioactivity over the lungs, possibly due to the accumulation of 125I fibrin in the lungs, followed by a rapid decline of radioactivity, suggestive of removal of fibrin from the lungs. Thromboplastin also caused a rapid decrease of systemic fibrinogen that was accompanied by a lengthening of the activated partial thromboplastin time and prothrombin time. The effect of coinfusion of rLACI with thromboplastin or bolus injection of rLACI before thromboplastin infusion was studied. At a high dose of rLACI (800 micrograms/kg body weight), the thromboplastin-induced radioactivity increase in the lungs and the systemic fibrinogen decrease were completely suppressed. The activated partial thromboplastin time and prothrombin time of the plasma samples lengthened, possibly due to the presence of thromboplastin in circulation. The thromboplastin-induced radioactivity increase over the lungs was not completely suppressed by lower doses of rLACI (135 to 270 micrograms/kg body weight), but these doses of rLACI prevented systemic fibrinogen decrease. At a bolus dose of 23 micrograms/kg body weight, rLACI provided 50% protection of the fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in rabbits treated with thromboplastin alone). These results show that rLACI is effective in the inhibition of thromboplastin-induced coagulation in vivo.

During a longitudinal study of vitamin C nutrition in 23 healthy elderly people, samples of cooked vegetables and liver, canned meats, canned vegetables and fruit drinks were analysed for vitamin C content. The analytical data are presented here and the effect on calculated daily intake of vitamin C of using the analytical values in place of food table values is assessed. For cooked foods the analysed values were close to food table values; exceptions were spring cabbage, cauliflower and canned potatoes. Fortified fruit drinks contained 20-60 mg vitamin C per 100 ml and made an important contribution to intake. Canned meats contained 0.3-61.4 mg per 100 g (mean 14.9 mg), but their contribution to intake was considered small. The difference between daily intakes calculated using analytical and food table values was greater than 5 mg in 37 per cent of 1-day periods and in 17 per cent of 7-day periods. These differences were not sufficient to significantly alter the correlations between intake and biochemical indices found in the original study. Nevertheless, given the discrepancies between calculated and analysed vitamin C intakes reported in the literature, analytical work is probably essential in studies of vitamin C nutrition.

The effect of maternal diet restriction on the subsequent development of four adipose tissue depots has been studied in the guinea pig. Fetuses taken from, and pups born to, pregnant sows fed ad libitum (AL) displayed an increase in fat pad mass and in fat cell mass with increasing body mass at the four selected depots (interscapular (IS), retroperitoneal (RP), groin side subcutaneous (GS) and behind arm subcutaneous (BA)). The effect of maternal diet restriction (50% AL rations during the second half of pregnancy) was to significantly reduce the body masses at birth of the pups. The masses of the BA and GS fat pads and the mass of fat cells in the depots were reduced accordingly. However, the fat depot masses and fat cell masses of the IS and RP fat pads were larger than those of pups of comparable body mass born to AL fed sows. Diet restriction during the second half of pregnancy exerted preferential 'sparing' effects on the 'thermogenic' adipose tissue depots (IS and RP) suggesting the possibility that 'thermogenic' adipose tissue is more likely to be 'programmed' earlier in pregnancy than 'storage adipose tissue' (BA and GS).

1. A modified heart rate (HR) method for predicting total energy expenditure (TEE) was cross-validated against whole-body calorimetry (CAL). Minute-by-minute HR was converted to energy expenditure (EE) using individual calibration curves when HR exceeded a pre-determined 'FLEX' value designed to discriminate periods of activity. ('FLEX' HR was defined as the mean of the highest HR during rest and the lowest HR during the lightest imposed exercise.) Sedentary EE (below FLEX) was calculated as the mean EE during lying down, sitting and standing at rest. Sleeping EE was calculated as basal metabolic rate (BMR) predicted from standard equations. 2. Calibration curves of oxygen consumption v. HR for different postures at rest and during exercise were obtained for twenty healthy subjects (eleven male, nine female); mean r 0.941 (SD 0.04). The mean FLEX HR for men and women were 86 (SD 10) and 96 (SD 6) beats/min respectively. 3. Simultaneous measurements of HR and EE were made during 21 h continuous CAL, which included 4 x 30 min imposed exercise (cycling, rowing, stepping, jogging). HR exceeded FLEX for a mean of 98 (SD 41) min. Mean TEE by CAL (TEE.CAL) was 8063 (SD 1445) kJ. 4. The HR method yielded a mean non-significant underestimate in TEE (TEE.HR) of 1.2 (SD 6.2)% (range -11.4 to +10.6%). Regression of TEE.HR (Y) v. TEE.CAL (X) yielded Y = 0.868 X + 927 kJ, r 0.943, SE of the estimate 458 kJ, n 20. 5. The satisfactory predictive power and low cost of the method makes it suitable for many field and epidemiological applications.

Mean nutrient intakes in eight families estimated using household measures were on average only 2 per cent greater than those based on semi-weighed method. The differences were significant for energy, fat, vitamin C and fibre. When the semi-weighed values for individual intakes of fat and sugar were substituted for the household measured values, the differences for fat and energy were no longer significant. Estimates of individual intakes based on household measures compared with those based on the semi-weighed method ranged from overestimates of 45 per cent to underestimates of 37 per cent.

Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.

The paper describes a computer program which calculates the amounts of each of 39 nutrients in a food, presented to it as a list of ingredients. Allowances can be made for losses of water and vitamins on cooking. The recipe can be compared with other foods already listed in the food tables. Other comparisons can also be made in terms of percent recommended daily intake. The new food may be retained as an addition to the food tables.

Information on food customs and recipes, collected from Indian, Pakistani and Bangladeshi immigrant women attending the Sorrento Maternity Hospital, in Birmingham, UK is presented. The calculated nutrient composition of these recipes is given, together with the composition of a number of Asian foods and spices taken from various food tables.

1. A method is described for the differentiation and determination of as little as 0.2mug. of vitamins D(2) and D(3) by gas-liquid chromatography. 2. The vitamins are converted by treatment with antimony trichloride into isovitamins D(2) and D(3), which show single, separate peaks on gas-liquid chromatography, unlike the unmodified vitamins, which give twin peaks due to the formation of pyro and isopyro derivatives. 3. Since isovitamins D(2) and D(3) remain together in all steps of the procedure except during gas-liquid chromatography, one may be used as an internal standard for the other. 4. The use of an internal standard reduces the importance of loss during sample preparation and increases precision. 5. The application of the method to biological materials is demonstrated.