PSORTb v.2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis.

MOTIVATION: PSORTb v.1.1 is the most precise bacterial localization prediction tool available. However, the program's predictive coverage and recall are low and the method is only applicable to Gram-negative bacteria. The goals of the present work are as follows: increase PSORTb's coverage while maintaining the existing precision level, expand it to include Gram-positive bacteria and then carry out a comparative analysis of localization. RESULTS: An expanded database of proteins of known localization and new modules using frequent subsequence-based support vector machines was introduced into PSORTb v.2.0. The program attains a precision of 96% for Gram-positive and Gram-negative bacteria and predictive coverage comparable to other tools for whole proteome analysis. We show that the proportion of proteins at each localization is remarkably consistent across species, even in species with varying proteome size. AVAILABILITY: Web-based version: http://www.psort.org/psortb. Standalone version: Available through the website under GNU General Public License. CONTACT: psort-mail@sfu.ca, brinkman@sfu.ca SUPPLEMENTARY INFORMATION: http://www.psort.org/psortb/supplementaryinfo.html.

Corticosteroid binding globulin, total serum cortisol, and stress in extremely low-birth-weight infants.

Our objective was to determine if low levels of corticosteroid binding globulin (CBG) might explain the low serum total cortisol levels found in some extremely low-birth-weight (ELBW) infants. In a prospective study, serum total cortisol and CBG were measured in single blood samples from 31 ELBW infants, with a gestational age less than 28 weeks, in the first 8 days of life. Severity of illness was assessed using the Score for Neonatal Acute Physiology Perinatal Extension (SNAP-PE). The mean serum total cortisol (mean +/- 1 SD) was 9.2 +/- 9.8 mcg/mL and the mean CBG level was 1.4 +/- 0.31 mg/dL. There was no significant correlation between serum total cortisol and CBG levels (r = -0.18), severity of illness as measured by the SNAP-PE (r = +0.12), or birth weight (r = -0.12). Five of 31 infants, having a mean SNAP-PE score of 41, had serum total cortisol levels < or = 3.0 mcg/dL. Estimated mean serum free cortisol concentrations in these five infants (0.76 mcg/dL) were comparable to estimated free cortisol levels diagnostic of adrenal insufficiency in sick adult patients. Our findings indicate that CBG levels are lower in ELBW infants than in term infants, but low CBG levels do not explain the low serum total cortisol levels found in some very sick infants. Low cortisol levels in small premature infants may be adequate to support growth if the infant is well, but may result in a syndrome of adrenal insufficiency in those with severe illnesses.

Interrelationships between the renin angiotensin system and uteroplacental blood flow--a recent perspective.

In pregnancy, the maternal circulating renin-angiotensin system (RAS) and uteroplacental tissue RAS has been thought to support maternal placental flow by raising maternal arterial pressure or changing placental vascular resistance. Also, the placenta or uterus may alter maternal circulating RAS. Recent studies in the authors' laboratory using chronically catheterized rabbits are compared with previous studies on interactions between the RAS and uteroplacental flow. When uterine driving pressure was reduced either mechanically or after converting enzyme inhibition, maternal placental flow decreased in proportion to change in driving pressure; myoendometrial flow did not change. Angiotensin II (AII) infusion to increase pressure by 21 +/- 2 mm Hg decreased placental but not myoendometrial flow. Thus, there is no evidence that maternal placental flow is autoregulated or supported by a specific renin-angiotensin mechanism. Normally, there is no net uterine release or uptake of active plasma renin activity, AI, or AII, but there is a small net release of trypsin-activated plasma renin activity (tPRA), presumably prorenin. Distal aortic occluder inflation produced upper-body hypertension, and uterine release of tPRA increased. There was a significant uterine arteriovenous concentration difference for AII during AII infusion. These methods are adaptable for studying interactions between uteroplacental flow and other vasoactive agents.

Maternal placental blood flow is reduced in proportion to reduction in uterine driving pressure.

The relationship between uterine driving pressure and maternal placental blood flow was studied after inflation of an aortic occluder previously placed between the renal and ovarian arteries in 10 conscious pregnant rabbits at 28 +/- 1 (mean +/- SEM) d of a 30- to 31-d gestation to test the hypothesis that there is autoregulation of maternal placental blood flow. After control measurements, the femoral artery pressure was reduced 22 +/- 3% from 83 +/- 5 mm Hg and clamped at 65 +/- 4 mm Hg (p < 0.001) for 54 +/- 4 min by servo control. Carotid artery pressure increased from 86 +/- 5 to 98 +/- 6 mm Hg (p < 0.01). There was no change in cardiac output (839 +/- 78 vs 814 +/- 64 mL/min; NS), upper-body flow (651 +/- 62 vs 671 +/- 55 mL/min; NS), or renal flow (111 +/- 14 vs 104 +/- 8 mL/min; NS). Blood flow to tissues below the occluder decreased from 188 +/- 18 to 143 +/- 14 mL/min for the lower body (p < 0.05), 153 +/- 15 to 116 +/- 11 mL/min for the hindquarters (p < 0.05), and 17.7 +/- 1.9 to 12.9 +/- 1.4 mL/min for 13 pregnant uterine horns (p < 0.05). Placental flow to live fetuses per horn decreased from 13.0 +/- 1.9 to 8.9 +/- 1.2 mL/min (p < 0.01), whereas there was no significant change in myoendometrial flow (4.0 +/- 0.3 vs 3.5 +/- 0.5 mL/min; NS). Uterine oxygen consumption was unchanged (1.15 +/- 0.16 vs 1.06 +/- 0.13 mL/min; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic pituitary adrenal function in the extremely low birth weight infant.

Extremely premature infants manifest clinical features suggestive of adrenal insufficiency. Yet, serum cortisol levels are similar in ill and well preterm infants in a setting where one would expect high stress levels in the ill infants. We investigated the hypothalamic-pituitary-adrenal axis in 17 extremely low birth weight stressed premature infants, mean birth weight 739 g, gestational age, 26.1 weeks, using ovine CRH (oCRH) and ACTH stimulation. oCRH (1 microgram/kg) was administered at 2-7 days of life (mean = 4.1). ACTH rose from a basal value 6.0 +/- 0.8 pmol/L (mean +/- SEM) to 9.6 +/- 1.8 pmol/L (P < 0.01) at 15 min and 9.5 +/- 1.7 pmol/L (P < 0.01) at 60 min. Basal cortisol rose from 349.3 +/- 58.1 nmol/L to 422.3 +/- 57.9 nmol/L (P < 0.01) at 15 min and 568.7 +/- 60.2 nmol/L (P < 0.01) at 60 min. Cortisol values remained significantly (P < 0.05) elevated 24 h after oCRH. An ACTH stimulation test performed 24 h after the oCRH test demonstrated a significant cortisol rise from 603.5 +/- 130.5 nmol/L to 882.7 +/- 136.6 nmol/L (P < 0.05) at 60 min. Plasma CRH immunoactivity was also measured before oCRH testing and was detectable in 10 of 15 infants. The mean CRH immunoactivity was 21.8 +/- 4.4 pmol/L in the infants, significantly higher than 8 adult male controls (P < 0.04). Our results show a normal pituitary response to ovine CRH and a normal adrenal response to ACTH. We hypothesize that cortisol levels are inappropriately low in some ill preterm infants because of the inability of the extremely premature brain to recognize the stress of the illness or because of inadequate hypothalamic secretion of CRH. The significance of the measurable plasma CRH in the first week of life is unknown.