Large scale identification of genes involved in cell surface biosynthesis and architecture in Saccharomyces cerevisiae

The sequenced yeast genome offers a unique resource for the analysis of eukaryotic cell function and enables genome-wide screens for genes involved in cellular processes. We have identified genes involved in cell surface assembly by screening transposon-mutagenized cells for altered sensitivity to calcofluor white, followed by supplementary screens to further characterize mutant phenotypes. The mutated genes were directly retrieved from genomic DNA and then matched uniquely to a gene in the yeast genome database. Eighty-two genes with apparent perturbation of the cell surface were identified, with mutations in 65 of them displaying at least one further cell surface phenotype in addition to their modified sensitivity to calcofluor. Fifty of these genes were previously known, 17 encoded proteins whose function could be anticipated through sequence homology or previously recognized phenotypes and 15 genes had no previously known phenotype.     

Stress, social support, and substantiated maltreatment in the second and third years of life

OBJECTIVE: The purpose of this research was to determine whether risk factors for a maltreatment report in the first year of life, especially the interaction of life event stress and social support, persist into the second and third years of life. METHOD: Predominantly low income mothers who had been interviewed shortly after the birth of infants in a longitudinal cohort were re-interviewed around the infants' first birthdays, and reports to North Carolina's Central Registry of Child Abuse and Neglect were tracked for substantiated maltreatment reports. RESULTS: Variables significantly associated with a substantiated maltreatment report in the second or third year of life (p < .01) were first year maltreatment reports and participation in Medicaid. Three interactions between a stressful life event indicator variable and a social support indicator variable were significant predictors of substantiated second or third year reports (p < .05). CONCLUSIONS: Even in the presence of significant risk factors from the first year of life, life event stress can increase the risk of a substantiated maltreatment report in the second or third years of life, but social support may moderate the effect of life events.     

Reoperative coronary bypass grafting without cardiopulmonary bypass through a small thoracotomy

BACKGROUND: The danger of coronary reoperations is mainly hidden in the reopening of the sternum and in the manipulation of the heart and the old grafts. Therefore, the minimally invasive direct coronary artery bypass procedure seems an ideal technique for coronary reoperations if only the left anterior descending coronary artery needs to be revascularized and the left internal mammary artery has not been used previously. METHOD: From January 1995 until May 1996 we performed 81 minimally invasive direct coronary artery bypass procedures through a small anterolateral thoracotomy in the fifth intercostal space, anastomosing the left internal mammary artery to the left anterior descending coronary artery. Six of these 81 were reoperative minimally invasive direct coronary artery bypass procedures on patients who had previously undergone coronary grafting through a median sternotomy with a vein graft to the left anterior descending coronary artery. RESULTS: Mean operation time was 85.8 +/- 22.2 minutes. Mean length of the mammary pedicles was 13 +/- 2 cm. Mean coronary occlusion time was 9.2 +/- 3.2 minutes. Mean postoperative hospital stay was 5.7 +/- 1.2 days (range, 5 to 8 days). No mortality and no cardiac-related morbidity were recorded. CONCLUSIONS: These results suggest that the technique is safe and promising in selected cases of reoperative coronary operation.     

Specific effects of estrogen on growth factor and major histocompatibility complex class II antigen expression in rat aortic allograft

OBJECTIVE: Transplant arteriosclerosis is the major determinant for long-term survival of cardiac transplants. Estradiol treatment inhibits transplant arteriosclerosis. The objective of this study is to determine, in the absence of immunosuppression, the temporal effect of estradiol treatment on the expression of insulin-like growth factor, platelet-derived growth factor, basic fibroblast growth factor, and major histocompatibility complex class II antigen in rat aortic allografts. METHODS: Orthotopic abdominal aortic allograft transplantation was performed in male rats with Brown-Norway rats used as donors and Lewis rats as recipients. The recipients (n = 50) were treated with estradiol 20 micrograms/kg per day or placebo by osmotic minipump for 2 days before the operation and until they were put to death on postoperative days 1, 3, 7, 14, or 21. The allografts were harvested and insulin-like growth factor, platelet-derived growth factor, basic fibroblast growth factor, and major histocompatibility complex class II antigen expression were determined by immunohistochemical staining. Myointimal thickening was measured by morphometric analysis. RESULTS: In the placebo-treated group, insulin-like growth factor protein progressively increased in all three layers of the allograft, whereas platelet-derived growth factor protein peaked at day 3 and basic fibroblast growth factor protein increased only moderately. Estradiol treatment inhibited the continuous increase in insulin-like growth factor expression, the peak in platelet-derived growth factor expression at day 3, the moderate-basic fibroblast growth factor increase at day 21, and major histocompatibility complex class II antigen expression in all three layers of the allograft at day 21. Intimal thickening of allografts from estradiol-treated recipients was twofold to threefold less than that of the placebo-treated recipients at day 21. CONCLUSION: The development of transplant arteriosclerosis is associated with an early alloimmune response involving sustained increase in insulin-like growth factor expression. Estradiol treatment of the recipient inhibits transplant arteriosclerosis and suppresses insulin-like growth factor and major histocompatibility complex class II antigen expression but not platelet-derived growth factor or basic fibroblast growth factor in all three layers of the allograft during the early posttransplantation alloimmune rejection phase.     

Bilateral lower limb oedema due to a distended urinary bladder

A 91-year-old Chinese man developed bilateral lower limb oedema due to venous obstruction resulting from a distended urinary bladder. After the bladder was decompressed by urethral catheterisation, the bilateral lower limb oedema promptly subsided. Although a distended urinary bladder is a rare cause of bilateral lower limb oedema, it can be easily recognised by palpation of the lower abdomen and the relief of symptoms by urethral catheterisation is most rewarding.     

Inhibition of prostaglandin production by nimesulide is accompanied by changes in expression of the cassette of uterine labor-related genes in pregnant sheep

The present study was designed to characterize effects of inhibiting PG production by infusing nimesulide (CAS 51803-78-2) on PGE2 production and expression of uterine labor-related genes in pregnant sheep. Myometrium, endometrium, and placenta were collected following 6 h of i.v. nimesulide or vehicle infusion. Infusions were commenced 9 h after onset of spontaneous term labor. Tissues were also collected from term control ewes not in labor. PGE2 was measured in fetal plasma by RIA. ER, OTR, Hsp 70 and 90, cPLA2, and PGHS-2 messenger RNA (mRNA) abundance in myometrium, endometrium, and PGHS-2 in placenta were quantified by Northern blot analysis. Fetal plasma PGE2 decreased during nimesulide infusion (P < 0.05). ER, OTR, Hsp 70, and Hsp 90 mRNA increased during spontaneous term labor in vehicle infused ewes in both myometrium and endometrium. In myometrium after nimesulide infusion, OTR and Hsp 70 mRNA decreased significantly (P < 0.05) compared with vehicle infused animals, but the decrease in Hsp 90 and ER mRNA fell outside the level of significance. In the endometrium, nimesulide produced a decrease in ER and OTR mRNA (P < 0.05) compared with vehicle infused animals, but the changes in Hsp 90 and 70 mRNA fell outside the level of significance. Nimesulide reversed the up-regulation of PGHS-2 mRNA that occurred in myometrium, endometrium, and placenta during vehicle infusion (P < 0.05). cPLA2 was only elevated in the endometrium in vehicle infused ewes and did not change in either endometrium or myometrium after nimesulide infusion. CONCLUSIONS: Inhibition of PG production resulted in decreased fetal plasma PGE2. The decreased abundance of mRNA for several of the well described cassette of utero-placental labor-related genes following nimesulide inhibition may result from altered PG production.     

Comparison of two outcome measures for infants with cerebral palsy and infants with motor delays

BACKGROUND AND PURPOSE: The purpose of this study was to compare the Gross Motor Function Measure (GMFM) and the Peabody Developmental Gross Motor Scale (PDMS-GM) as measures of change in infants with cerebr-al palsy (CP) and infants with motor delays. We hypothesized that mean change scores would be greater for the GMFM than for the PDMS-GM. SUBJECTS AND METHODS: Subjects were 42 infants with a mean adjusted age of 13.9 months (SD=6.1, range=4.2-24.2). Twenty-four infants had CP, and 18 infants had motor delays. The GMFM and the PDMS-GM were administered to the infants 3 times over a 6-month period. Raw scores were standardized for data analysis. Data were analyzed using a 3-factor repeated-measures analysis of variance. RESULTS: For the 6-month period, mean PDMS-GM age-equivalent scores increased 3.8 months and mean scaled scores increased 35 points for infants with motor delays compared with increased scores of 1.8 months and 13 points for infants with CP. Mean GMFM scores increased by 12.2% for infants with rmotor delays and by 4.2% for infants with CP. The diagnosis X time interaction was significant. Infants with motor delays had a greater change in motor development compared with the infants with CP. The hypothesis that the GMFM is more responsive to change than the PDMS-GM was not supported. CONCLUSION AND DISCUSSION: The findings suggest that the GMFM and the PDMS-GM are comparable in measuring change in infants with CP or motor delays. Implications for selection and use of either measure are discussed.     

Interactions of EGF, Wnt and HOM-C genes specify the P12 neuroectoblast fate in C. elegans

We investigate how temporal and spatial interactions between multiple intercellular and intracellular factors specify the fate of a single cell in Caenorhabditis elegans. P12, which is a ventral cord neuroectoblast, divides postembryonically to generate neurons and a unique epidermal cell. Three classes of proteins are involved in the specification of P12 fate: the LIN-3/LET-23 epidermal growth factor signaling pathway, a Wnt protein LIN-44 and its candidate receptor LIN-17, and a homeotic gene product EGL-5. We show that LIN-3 is an inductive signal sufficient to promote the P12 fate, and the conserved EGF signaling pathway is utilized for P12 fate specification; egl-5 is a downstream target of the lin-3/let-23 pathway in specifying P12 fate; and LIN-44 and LIN-17 act synergistically with lin-3 in the specification of the P12 fate. The Wnt pathway may function early in development to regulate the competence of the cells to respond to the LIN-3 inductive signal.