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V Austin

Publications and source records attributed to V Austin.

9 recordsLinked to original sources

Intake of major nutrients by women in the Maternal Phenylketonuria (MPKU) Study and effects on plasma phenylalanine concentrations.

BACKGROUND: Women with untreated phenylketonuria (PKU) often have poor reproductive outcomes. OBJECTIVE: We assessed the effects of intakes of major nutrients on plasma phenylalanine concentrations and we measured phenylalanine hydroxylase activity and phenylalanine intakes in pregnant women with PKU. DESIGN: Dietary intakes and plasma phenylalanine concentrations were compared in 4 subject groups defined on the basis of plasma phenylalanine concentrations: group 1 (n = 23), <360 micromol/L by 10 wk gestation and 120-360 micromol/L throughout the remainder of pregnancy; group 2 (n = 46), <600 micromol/L but not <360 micromol/L by 10 wk gestation and 120-600 micromol/L throughout the remainder of pregnancy; group 3 (n = 24), <600 micromol/L by 10 wk gestation but >600 micromol/L at least once thereafter; group 4 (n = 147), never <600 micromol/L. RESULTS: Except in the first trimester, mean intakes of phenylalanine, energy, and fat tended to be greater in group 1 than in the other groups. The mean protein intake of group 1 tended to be greater than that of the other groups. Intakes of protein (P < 0.0001), fat (P < 0.0001), and energy (P < 0.007) were negatively correlated with maternal plasma phenylalanine concentrations. It appeared that genotype did not affect phenylalanine tolerance. CONCLUSIONS: Maternal genotype appeared to have little influence on phenylalanine requirements during the first trimester. Early decline and maintenance of maternal plasma phenylalanine concentrations at <360 micromol/L and mean protein intake greater than the recommended dietary allowance (RDA) with mean energy intake near the RDA resulted in the best reproductive outcomes. Inadequate intakes of protein, fat, and energy may result in elevated plasma phenylalanine concentrations and may contribute to poor reproductive outcomes.

Diet Records↗

Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria.

OBJECTIVE: To test the efficacy of tyrosine supplementation, as an adjunct to dietary treatment, on neuropsychological test performance in individuals with phenylketonuria. DESIGN: A randomised controlled trial of tyrosine supplementation using a double blind crossover procedure with three four week phases. SETTING: The Hospital for Sick Children, Toronto. PARTICIPANTS: 21 individuals with phenylketonuria (ages 6 to 28 years, mean 11.3). INTERVENTION: Participants were given 100 mg/kg body weight/d of L-tyrosine or L-alanine (placebo). RESULTS: At baseline, performance on several of the neuropsychological test measures was correlated with tyrosine levels. Dietary supplements of tyrosine increased plasma tyrosine concentrations; however, no change in test performance was found across the tyrosine and placebo phases of the study. CONCLUSIONS: Tyrosine supplementation of this type does not appear to alter neuropsychological performance in individuals with phenylketonuria.

Administration, Oral↗

Nutrition and reproductive outcome in maternal phenylketonuria.

Maternal weight gain and intake of selected nutrients were correlated with plasma phenylalanine (Phe) concentrations and reproductive outcomes (in 150 and 142 subjects respectively) in the Maternal PKU Collaborative Study. Daily protein intake was negatively correlated with plasma Phe concentration. Birth length, weight and head circumference of offspring were negatively influenced by the length of time required for the maternal plasma Phe to decline below 600 mumol/l (10 mg/dl) and positively influenced by weight gain of mother as a percentage of recommended weight gain. Birth weight and length were positively correlated with maternal protein and energy intakes. During the first trimester, intakes of fat, calcium, phosphorus, vitamin A and folate were significantly greater in women who had a good reproductive outcome than by women who had a poor outcome. In addition to plasma Phe control in maternal phenylketonuria (PKU), maternal weight gain and dietary intake of protein, energy and fat were correlated with outcome. Therefore, nutrient intake and maternal weight gain should be considered along with plasma Phe concentration when managing the therapy of a pregnant woman with PKU.

Diet, Protein-Restricted↗

Ras transformation of cloned rat embryo fibroblasts results in increased rates of protein synthesis and phosphorylation of eukaryotic initiation factor 4E.

Eukaryotic initiation factor 4E (eIF-4E) is a 25-kDa phosphoprotein that binds to the 7-methylguanosine cap of mRNA and acts, along with other eIF-4 polypeptides, to unwind mRNA secondary structure at the 5' terminus. Recent studies have indicated that eIF-4E acts as a protooncogene, but only in its phosphorylated state. In order to determine the role of eIF-4E in oncogenesis, we examined its regulation and expression in cloned rat embryo fibroblasts transformed with the Harvey ras (Ha-ras) oncogene. The expression of Ha-ras increased the rate of protein synthesis but did not increase the levels of eIF-4E mRNA or protein. However, a dramatic increase (7-fold) in phosphate incorporation into eIF-4E was observed. The percentage of eIF-4E in the phosphorylated state was the same in transfected and control cells, indicating that both phosphorylation and dephosphorylation of eIF-4E were increased. Phosphopeptide mapping of eIF-4E from transformed cells indicated a single site of phosphorylation at Ser-53, which is the same as that identified previously in eIF-4E from reticulocytes and HeLa cells. These results indicate that p21ras is part of the signal transduction pathway leading to phosphorylation of eIF-4E. These findings also provide a potential mechanism for cell transformation by p21ras which involves the preferential stimulation of translation of certain mRNAs.

Animals↗

The effects of shear stress and metastatic phenotype on the detachment of transformed cells.

A parallel-plate flow chamber was used to quantify the detachment of normal, transformed, and reverted rat fibroblasts from a confluent monolayer of normal fibroblasts. In this method, known shear stresses were applied to the adherent cells and the percent of cells detached from the monolayer was determined. Results indicate that the detachment of all cell types increased with increasing shear stress and detachment of highly metastatic ras-transformed cells was significantly higher than that of either nonmetastatic normal cells or transformed cells reverted with the Kirsten ras revertant (K-rev 1a) gene, which are lowly metastatic. From these results, it is concluded that a correlation exists between the metastatic phenotype of the cell and its ability to detach from normal cells.

Animals↗

The diagnostic interview for borderline patients.

The authors describe the content, administration, reliability, construct validity, and training requirements for a semistructured diagnostic interview for borderline patients. The interview is composed of operationally defined and scored variables that assess five areas of functioning considered most characteristic of borderline patients--social adaptation, impulse/action patterns, affects, psychosis, and interpersonal relations. Their results show that the interview provides a reasonably constructed and reliable method for researchers and clinicians interested in identifying the syndrome of borderline personality disorders. Although existing research supports the clinical utility of defining borderline patients with the diagnostic interview for borderline patients, both the diagnosis and the content of the interview may require revisions.

Borderline Personality Disorder↗

The influence of the presence of adenovirus 5 E1a and E1b sequences on the pathology of rat embryonic fibroblasts transfected with activated c-Ha-ras and v-ras.

We compared the pathology of two groups of tumors following implantation of cells enmeshed in alginate beads into the syngeneic rat. The first group of tumors was generated by implanting alginate beads containing cloned embryonic fibroblasts (CREF) that were transfected with activated c-Ha-ras (T24) and v-ras (pH1) (CREF tumors). The second group was created by implantation of CREF cells that were transfected with E1a and E1b of wild type adenovirus type 5 prior to transfection with T24 and pH1 (Wt tumors). Alginate beads were implanted at three different sites in the rat, i.e. subcutaneous in the flank, subcutaneous in the tail and under the renal capsule. Tumorigenicity, invasiveness and metastatic capacity of the transfectant cell lines were determined. The tumor latency period (TLP), the doubling time of the tumors and the metastatic capacity of the cell lines depended on the site of implantation. Invasion was not influenced by site-dependency. Wt tumors were invasive and generally had longer TLP than the CREF tumors. Wt tumors did not metastasize to the lungs as opposed to CREF tumors. We concluded that the genetic background of Wt cells modulated the effect of ras transfection by stretching the TLP and by limiting the metastatic potential to the draining lymph nodes. Malignancy per se was not repressed since no differences in invasive capacity were noticed.

Adenoviruses, Human↗