PHI-DAC: protein homology database through dihedral angle conservation.

UNLABELLED: Finding related conformations in the Protein Data Bank is essential in many areas of bioscience. To assist this task, we designed a dihedral angle database for searching protein segment homologs. The search engine relies on encoding of the protein coordinates into text characters representing amino acid sequence, φ and ψ dihedral angles. The search engine is advantageous owing to its high speed and interactive nature and is expected to assist scientists in discovering conformation homologs and evolutionary kinship. The search engine is fast, with query times lasting a few seconds, and freely available at http://tarshish.md.biu.ac.il/∼samsona. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Correlation of maternal serum and amniotic fluid leptin and insulin levels with neonatal birth weight].

BACKGROUND: Numerous studies correlated maternal serum and fetal cord Leptin Levels in pregnancy with new born weight (NBW) and maternal body mass index (BMI). However, there are only a few published studies concerning amniotic fluid leptin and its possible relationship to fetal growth and NBW. OBJECTIVES: To correlate leptin and insulin in amniotic fluid and maternal serum collected at 16-20 gestational weeks to NBW. METHODS: This was an observational study in which maternal serum Leptin, insulin, and amniotic fluid Leptin and insulin, studied from 70 healthy pregnant women undergoing amniocentesis for karyotyping, at 16-20 weeks gestation. NBW was correlated with maternal BMI and leptin and insulin Levels in maternal serum and amniotic fluid. RESULTS: Maternal serum leptin was detected as the best predictor of NBW. Squared correlation coefficient, r2 = 0.09, was statistically significant (P < 0.01). Maternal BMI correlated significantly with serum Levels of insulin and leptin r2 = 0.16 and 0.27 respectively, P < 0.01. CONCLUSION: In normal pregnancies, amniotic fluid Leptin correlates partially with NBW. Maternal serum leptin correlates significantly with NBW.

Periodontal care may improve systemic inflammation.

BACKGROUND: Periodontitis is an infectious chronic insidious disease of the tooth supporting structures that causes a general inflammatory response. The aims of the study were to determine whether periodontitis is associated with markers of general inflammation high-sensitivity (hs) C-reactive protein (CRP) leading to cardiovascular disease, and whether proper management of the periodontal disease would improve inflammation and thus, may prevent cardiovascular disease in the future. METHODS: This was a prospective case-controlled pilot study. Nine patients (3 women, 6 men; 40+/-5 yr) took part. All had severe periodontitis, without systemic disorders, and were all treated conservatively without surgical intervention. All had a 2nd visit after 3 months of treatment at the Outpatient Dental Clinic of the Hospital. Periodontal status and hs-CRP were evaluated on entry to the study and 3 months after treatment. Nine age and sex-matched healthy volunteers without periodontal disease served as the control group. RESULTS: Periodontal clinical parameters were improved after 3 months' treatment: probing depth (PD) (mean) at baseline was 4.3 and after 3 months' treatment improved to 3.2 (P=0.001), clinical attachment level (CAL) (mean) was 4.6 and changed to 3.7 (P=0.01), bleeding on probing (BOP %) changed from 64% to 33% (P=0.001), and Plaque index (Pi) changed from 49% to 25% (P=0.001). hs-CRP level was different between the patients'group (pre treatment) and the healthy volunteers: 2.97+/-0.58 mg/L vs. 0.25+/-0.14 mg/L (P=0.00002). After completing 3 months' treatment, hs-CRP levels were decreased from 2.97+/-0.58 mg/L to 2.3+/-0.7 mg/L (P=0.009). CONCLUSIONS: Periodontitis is an infectious condition that may be an insidious cause of chronic inflammation and may be a risk factor for future cardiovascular disease. Treating periodontitis improved inflammation, and might be used as an important prevention tool for cardiovascular disease.

Tomato-rich (Mediterranean) diet does not modify inflammatory markers.

BACKGROUND: The Mediterranean diet is rich in lycopene and has been reported to reduce cardiovascular events. The mechanism of prevention of cardiovascular events has not been clearly established. Our aim was to study the effects of a tomatoes-rich diet on markers of vascular inflammation. METHODS: Plasma concentrations of E-selectin, intercellular adhesion molecule 1 (ICAM-1), and high sensitivity C-reactive protein (hs-CRP) were determined by ELISA in 103 apparently healthy volunteers. Volunteers were randomly assigned to two groups: 50 participants ate 300 g tomatoes daily for 1 month, and 53 participants ate their usual diet with tomatoes prohibited during that period. Markers of inflammation were measured before enrollment and 1 month after their assigned diet. RESULTS: The two diet groups had similar baseline clinical characteristics and similar baseline levels of inflammatory markers. After 30 days of assigned diet concentrations of hs-CRP, E-selectin and ICAM-1 were unchanged compared with baseline in the tomato-rich diet. However, ICAM-1 concentration was increased in the regular diet group from 247.55+/-55 ng/ml to 264.71+/-60.42 ng/ml (P=0.01). CONCLUSIONS: The mechanisms of benefit of the tomato-rich diet are not directly related to inhibition of markers of vascular inflammation.

The stroke trial - can we predict clinical outcome of patients with ischemic stroke by measuring soluble cell adhesion molecules (CAM)?

BACKGROUND: Several studies have found that an increased concentration of haemostatic or inflammation markers was associated with worse prognosis in vascular disease. The inflammatory components in ischemic stroke are of current interest, and there is some experimental evidence that they may be linked. HYPOTHESIS: The study was performed to determine the association between the neurological clinical outcome and levels of cell adhesion molecules in the first four days of hospitalization in patients with acute ischemic event. METHODS: This prospective, pilot, case-controlled study examined the association between the clinical outcome and inflammatory markers within the first few days of hospitalization. The neurological evaluation was performed using the NIH score on admission and four days later, and levels of cell adhesion molecules were measured by ELISA methods on admission and four days later. RESULTS: Twenty three patients with an acute cerebral event (mean age 71 +/- 15 y, 12 women and 11 men) were examined neurologically on admission and four days later. Among 19 patients who improved, there was a significant decrease in the NIH neurological scale, from 3.8 +/- 3.2 to 1.3 +/- 1.8 (p = 0.01), which was accompanied by a significant decrease in the cell adhesion molecules that were measured (E-selectin, ICAM-1 and VCAM-1). Of the four patients who did not improve, their mean clinical NIH score was 10 +/- 4.6 and worsened or remained unchanged after four days of follow-up. In this group, we could not demonstrate a significant change in levels of cell adhesion molecules between days one and four. CONCLUSIONS: Patients who improved clinically within the first four days of hospitalization demonstrated a remarkable inhibition of all three cell adhesion molecules that were measured (E-selectin, ICAM-1, and VCAM-1). Patients who did not improve had more severe cerebral infarcts, a higher NIH score on admission (10 +/- 4.6), and no change was observed in levels of cell adhesion molecules during the follow-up period. Measuring cell adhesion molecule levels may predict objectively the clinical outcome in hospitalized patients with acute ischemic stroke.

Calponin levels in term laboring women.

OBJECTIVE: Calponin, a specific smooth muscle contraction regulatory troponin-like protein, is present in large quantities in uterine smooth muscle. Serum troponin levels rise in acute myocardial infarction, and creatine phosphokinase levels rise at high physical activity, both due to destruction of cardiac and striated muscle fibers. We hypothesize that the active labor process may cause uterine smooth muscle cell damage, which may result in rising maternal serum calponin levels. This was a preliminary study, searching for a new biomarker for preterm labor. METHODS: The study group included laboring term primiparous women with a singleton fetus. The control group included similar demographic and pregnancy characteristics pregnant women not in labor. Maternal serum levels of calponin basic isoform were measured evaluated and compared in both groups. RESULTS: Study group included 100 pregnant women. Calponin serum levels were higher in the active labor (794 ± 974 ng/mL) than in the group not in labor (591 ± 587 ng/mL), although it did not reach statistical significance. Gender and neonatal weight were similar in the two study groups. CONCLUSIONS: Calponin serum levels showed moderate elevation during active labor, compared to the levels in a cohort of pregnant comparable women at the same gestational weeks but not in labor.

Effects of oral soy protein on markers of inflammation in postmenopausal women with mild hypercholesterolemia.

BACKGROUND: Nitric oxide (NO) may protect arteries against atherosclerosis, as suggested by experimental studies. Estrogen therapy enhances the bioactivity of NO in the vasculature of healthy postmenopausal women, but is not acceptable for long-term use by many women. Observational studies have demonstrated beneficial cardiovascular effects of soy protein in premenopausal and postmenopausal women. We examined whether the consumption of isolated soy protein may improve markers of vascular inflammation in postmenopausal women with hypercholesterolemia. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled, crossover study, 24 postmenopausal women with hypercholesterolemia received 25 g of soy protein or a placebo daily for 6 weeks, with treatment periods separated by 1 month. Markers of vascular inflammation were measured by enzyme-linked immunosorbent assay methods, including: soluble interleukin-2 receptor (sIL-2r), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). There was no effect of soy protein in comparison with placebo on the inflammatory markers: the sIL-2r level was 942.2 +/- 335.3 pg/mL with soy protein and 868.5 +/- 226.9 pg/mL with placebo (P =.311); E-selectin was 39.6 +/- 16.5 ng/mL with soy protein and 42.1 +/- 17.6 ng/mL with placebo (P =.323); P-selectin was 157.9 +/- 67.9 ng/mL with soy protein and 157.5 +/- 47.6 ng/mL with placebo, (P =.977); ICAM-1 was 266.0 +/- 81.3 ng/mL with soy protein and 252.5 +/- 82.7 ng/mL with placebo (P =.435); VCAM-1 was 402.7 +/- 102.1 ng/mL with soy protein and 416.4 +/- 114.8 ng/mL with placebo (P =.53). CONCLUSIONS: Consumption of 25 g of isolated soy protein daily for 6 weeks does not substantially affect markers of vascular inflammation in postmenopausal women with hypercholesterolemia.

The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis.

OBJECTIVE: To estimate whether the risk of neonatal thyrotoxicosis was related to the value of maternal thyroid-stimulating immunoglobulin in women with Graves disease. METHODS: The records of pregnant women undergoing testing for thyroid-stimulating immunoglobulin over a 10-year period were analyzed. Neonatal thyrotoxicosis was defined as the presence of tachycardia, goiter, hydrops, tremulousness, voracious appetite, irritability, cardiomegaly, or congestive heart failure, with elevated thyroid hormone levels. The relationship between maternal thyroid-stimulating immunoglobulin values and the development of thyrotoxicosis was examined. The sensitivity, specificity, and positive and negative predictive values were calculated using an arbitrarily chosen cutoff for thyroid-stimulating immunoglobulin. RESULTS: Twenty-nine women with a history of Graves disease and positive thyroid-stimulating immunoglobulin values were available for analysis. Of the 35 live births, there were six cases of neonatal thyrotoxicosis (17.1%). A maternal thyroid-stimulating immunoglobulin value at least 5 index units predicted neonatal thyrotoxicosis with a sensitivity of 100%, specificity of 76.0%, positive predictive value of 40.0%, and negative predictive value of 100%. CONCLUSION: Pregnancies complicated by high values of maternal thyroid-stimulating immunoglobulin appear to be at risk of developing neonatal thyrotoxicosis.

Serum corin is reduced and predicts adverse outcome in non-ST-elevation acute coronary syndrome.

BACKGROUND AND OBJECTIVES: The aim of the current study was to describe the role of corin, an enzyme that cleaves pro-atrial natriuretic peptide and pro-brain natriuretic peptide into their active peptides, in patients with acute coronary syndrome (ACS). METHODS: Serum corin level was studied in patients with non-ST-elevation ACS who underwent percutaneous coronary intervention (n=152) and in control volunteers (n=103). RESULTS: The corin level was lower in acute coronary syndrome patients (798±288 pg/ml) than in the controls (1165±613 pg/ml, p<0.0001). Those acute coronary syndrome patients who developed major adverse cardiovascular events (MACE; 60.9%) within 3 years of discharge had lower corin levels than the patients who did not experience major adverse cardiovascular events (698.16±233.67 vs. 952.1±297.81 pg/ml, p<0.0001). Using a multiple logistic regression model, corin level was a significant predictor of post-ACS MACE: p=0.0004 for 50 pg/ml steps, AUC 0.791, while p<0.0001, and AUC 0.804 using corin and brain natriuretic peptide as predictors. CONCLUSIONS: Patients with non-ST-elevation ACS have lower serum corin levels than controls. Corin levels are lower in ACS patients who later experience MACE and thus might be predictor for MACE. This new putative biomarker may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment and outcome prediction in ACS patients.

Vascular inflammation and endothelial dysfunction in fracture healing.

Angiogenesis is an important step in bone fracture healing. In this article, we report on the healing of long bone fractures, and the involvement of the vascular and the inflammatory systems in the process. We conducted a prospective study of 20 healthy adults with traumatic long bone fracture. One week after fracture, and then 1 month later, we evaluated markers of inflammation: vascular responsiveness (brachial endothelial function and ankle brachial index) and inflammatory and cytokine levels osteopontin [OPN], E-selectin, and vascular endothelial growth factor [VEGF]). Long bone fractures caused intense vascular and inflammatory responses, represented by high levels of OPN, Eselectin, and VEGF. In vivo measurements demonstrated severe endothelial dysfunction, which could support the idea that the vascular system is recruited to build new blood vessels that support bone regeneration.

Endothelial progenitor cells are suppressed in anemic patients with acute coronary syndrome.

OBJECTIVE: Anemia is an independent predictor of poor prognosis in acute coronary syndrome. Endothelial progenitor cells are bone marrow-derived cells that are mobilized into the circulation in response to ischemia. The number of circulating endothelial progenitor cells increases within days of acute coronary syndrome. There is no confirmation regarding the correlation between the occurrence of anemia and the deficiency in endothelial progenitor cells in patients with acute coronary syndrome. The correlation between chronic anemia and endothelial progenitor cells in patients with acute coronary syndrome was investigated. METHODS: Endothelial progenitor cells were examined in 26 patients with acute coronary syndrome. Fifteen patients had chronic nonprogressive anemia, and 11 patients had a normal blood count. Blood samples were drawn on the first day of admission and 4 to 7 days later. Mononuclear cells were separated and cultured on fibronectin-coated plates with EndoCult medium (StemCell Technologies, Vancouver, BC, Canada) for 5 days. Colony forming unit count and a migration assay were performed at each time point. RESULTS: Baseline colony forming unit in the non-anemic group was higher than in the anemic group (P<.0001). There was a highly significant correlation between admission hemoglobin and colony forming unit count (R=0.83, P<.0001). Colony forming units increased in both groups on the second measurement but to a lower extent in the anemic group (P = .0004). The migration assay in the non-anemic group was higher than in the anemic group at baseline (P = .017) and 4 to 7 days later (P = .0054). CONCLUSION: Patients with acute coronary syndrome with anemia demonstrate a reduced number of peripheral endothelial progenitor cells with impaired function, possibly representing a lower capacity for vascular healing. These phenomena may partly explain the poor prognosis observed in patients with acute coronary syndrome and anemia.

Enzyme-linked immunoabsorbent assay for detection of human serine protease corin in blood.

BACKGROUND: Corin is a tissue type II transmembrane protein that converts pro-atrial natriuretic peptides and pro-brain natriuretic peptide to their active forms. Despite their protecting effect, high levels of these peptides indicate a bad prognosis. One of the possible explanations to this paradox is reduced cleavage due to low corin levels. The purpose of this study was to develop an assay to detect blood levels of corin. METHODS: ELISA was developed using rat monoclonal antibody to recombinant human corin as capture antibody, and biotinylated goat anti-human corin as detection antibody. RESULTS: Based on known corin concentration as standards, the ideal capture antibody concentration was 500 ng/ml, and 200 ng/ml for detection antibody. The coefficient of variation was 5.7% for inter-assay and 3.9% for intra-assay precision. Corin levels were stable when stored at room temperature for 1 day, for 3 days at 4 degrees C or up to 1 year in -35 degrees C. Human serum corin levels were reproducibly measured in individuals and found to range from 296 to 2590 pg/ml. CONCLUSIONS: The immunoabsorbent assay developed in this study can accurately and reliably determine human serum corin levels, and is suitable for simple screening of corin in clinical practice.

Loss of systemic endothelial function post-PCI.

Loss of endothelial function (LEF) post-PCI may contribute to both acute and long-term complications. A protective effect of BNP on endothelium was suggested previously. Flow-mediated vasodilation (FMD) of the brachial artery, as well as plasma levels of endothelin, BNP, Pro BNP and corin were measured before and following routine PCI. 49 patients with normal baseline endothelial function were recruited. 30 patients developed LEF and were randomized to i.v. nesiritide (the commercially available recombinant form of human BNP) or saline infusion for 3 h. Patients who developed LEF post-PCI had reduced baseline plasma corin levels and their BNP/ProBNP ratio was reduced after the procedure. Nesiritide infusion significantly improved FMD both immediately (Nesiritide versus saline: 2.87+/-0.78% versus 0.51+/-0.25%, P=0.007) and 24 h after the treatment (2.52+/-0.69% versus 0.72+/-0.32%, P=0.025). The elevated plasma ET-1 was reduced by Nesiritide (0.38+/-0.11 fmol/ml 24 h post-PCI versus 0.16+/-0.02 fmol/ml 24 h post BNP, P=0.047), but remained unchanged in saline group (0.39+/-0.21 fmol/ml versus 0.42+/-0.23 fmol/ml, P=0.749). Systemic LEF post-PCI is a frequent event. It may be related to impaired cleavage of ProBNP to BNP. Short-term i.v. nesiritide improves systemic LEF post-PCI.

Endothelial function in patients with sickle cell anemia during and after sickle cell crises.

BACKGROUND: Prior studies have demonstrated increased adherence of sickle cell erythrocytes to vascular endothelial cells. While decreased production of nitric oxide and increased production of adhesion molecules have been implicated in this pathophysiology, the relative contribution of these mechanisms during acute sickle cell crises as compared to steady state conditions have not been elucidated. METHODS AND RESULTS: We studied 10 consecutive young adult patients presenting with a sickle cell crisis. Endothelial function was evaluated by a non-invasive brachial artery shear stress method. Serum levels of adhesion molecules were obtained during the crisis. Both brachial artery responsiveness and serum levels of adhesion molecules were then repeated at steady state. Ten age and gender matched volunteers served as a control group. Impaired endothelial function and impaired endothelium-independent vasodilatation were observed in all sickle cell patients during both steady state and during crisis. Flow mediated dilation (FMD)% was 3.25+/- 2.76% during crisis, 4.57+/- 4.11 at steady state, compared with the control group FMD of 11.64+/- 7.69% (p< 0.001). Flow independent dilation was 10.35+/- 11.3% during crisis, 10.03+/- 6.52% at steady state, compared with control group FID of 24.17+/- 11.87% (p< 0.001). Levels of cell adhesion molecules and markers of inflammation were increased in sickle cell crisis patients compared with the control group: sCD40 ligand levels during the acute crisis were over twice the level of normal matched volunteers (p=0.02), and similarly significant increases were seen for E-selectin (p=0.008), ICAM-1 (p=0.037) and VCAM-1 levels (p=0.01). The levels of each of these biomarkers was not significantly increased during acute crises as compared to patients' recovery state. CONCLUSIONS: Sickle cell anemia patients have severe systemic endothelial dysfunction as demonstrated by both brachial artery assessment and increased serum levels of adhesion molecules. These abnormalities characterize not only the sickle cell crisis but also the steady state pathophysiology of sickle cell anemia.

Effects of soy protein on endothelium-dependent vasodilatation and lipid profile in postmenopausal women with mild hypercholesterolemia.

BACKGROUND: Estrogens appear to improve endothelium-dependent systemic and coronary vasodilator function, perhaps by increasing nitric oxide levels and the subsequent effect of nitric oxide on endothelial function and smooth-muscle relaxation. Because soybean foods contain phytoestrogens, we evaluated the effect of orally administered soy proteins on vascular responsiveness. METHODS: This double-blind, placebo-controlled crossover study involved 24 postmenopausal women (mean age 55 yr) who were hypercholesterolemic, who were not taking hormone replacement therapy and had not taken antioxidants or lipid-lowering agents in the preceding 2 months. The patients were randomized to receive a 25-g soy protein supplement or a mild protein placebo for 6 weeks, separated by a washout period of 4 weeks. To evaluate nitric oxide bioactivity we used ultrasonography to measure endothelium-dependent dilator responses in the brachial artery to hyperemia. We induced hyperemia by inflating a blood pressure cuff on the forearm to 250 mm Hg for 5 minutes. We also determined the effect of the supplements on various lipids. RESULTS: The mean (+/- standard deviation) brachial artery diameter was similar in both groups (3.94 [0.79] mm in the placebo group and 4.13 [0.74] mm in the soy protein group). In both placebo and protein groups, the serum triglyceride levels increased, and total cholesterol and low-density lipoprotein cholesterol levels fell significantly (p < 0.05). High-density lipoprotein cholesterol levels were little changed. INTERPRETATION: Consumption of a supplement of 25 g of soy protein daily for 6 weeks had no measurable effect on arterial diameter or vasodilatation in response to hyperemia.