Characterization of antimicrobial peptides from the skin secretions of the Malaysian frogs, Odorrana hosii and Hylarana picturata (Anura:Ranidae)

Peptidomic analysis of norepinephrine-stimulated skin secretions from Hose's rock frog Odorrana hosii (Boulenger, 1891) led to the isolation of 8 peptides with differential antibacterial activities. Structural characterization demonstrated that the peptides belonged to the esculentin-1 (1 peptide), esculentin-2 (1 peptide), brevinin-1 (2 peptides), brevinin-2 (2 peptides), and nigrocin-2 (2 peptides) families of antimicrobial peptides. Similar analysis of skin secretions from the Malaysian fire frog Hylarana picturata (Boulenger, 1920) led to the isolation and characterization of peptides belonging to the brevinin-1 (2 peptides), brevinin-2 (5 peptides), and temporin (1 peptide) families. The differences in antimicrobial activities of paralogous peptides provide insight into structure-activity relationships, emphasizing the importance of cationicity in determining potency. The substitution Lys(11)-->Gln in brevinin-1HSa (FLPAVLRVAAKIVPTVFCAISKKC) from O. hosii abolishes growth inhibitory activity against Escherichia coli but has no effect on the high potency (MIC=8mug/ml) against Staphylococcus aureus. In contrast, the substitution (Gly(4)-->Asp) in brevinin-2PTb (GFKGAFKNVMFGIAKSAGKSALNALACKIDKSC) from H. picturata reduces activity against both E. coli and S. aureus. Cladistic analysis based upon the amino acid sequences of the brevinin-2 peptides from Asian frogs provides evidence for sister taxon relationships between O. hosii and O. livida and between H. picturata and H. güntheri.     

TP53 mutation and survival in aggressive B cell lymphoma

TP53 is mutated in 20–25% of aggressive B‐cell lymphoma (B‐NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B‐NHL, we investigated TP53 gene mutations within the RICOVER‐60 trial. Of 1,222 elderly patients (aged 61–80 years) enrolled in the study and randomized to six or eight cycles of CHOP‐14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index‐Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B‐symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event‐free (EFS), progression‐free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI‐factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed.     

Spontaneous regression of a breast carcinoma: a case report

Spontaneous regression of malignant tumors is a rare event. It is defined as partial or total disappearance of a proven malignant tumor without adequate medical treatment. The causes of this phenomenon are various. Nevertheless, malignant tumors do regress occasionally for no apparent reason, as evidenced by many clinical observations. We report a case of a 68-year-old woman, who was presented with a several-month history of a painless firm lump, initially of 1 cm in diameter and growing to a large solid regular tumor of 2.5 x 2.5 cm in size, in the upper outer quadrant of her right breast. Preoperative histopathological diagnosis revealed ductal invasive carcinoma. Later on, while awaiting surgical treatment, she suffered an arm injury requiring a 1-month delay of surgery. After recovery, on the date of surgery the tumor disappeared, and, in addition, it was not found in tissue specimens obtained from quadrantectomy. After 78 months of follow-up there was no evidence of relapse. In this report, we discuss clinical and histopathological findings, patient management and possible mechanisms of cancer regression.     

Maternal serum concentration of angiogenic factors: PIGF, VEGF and VEGFR-1 and placental volume in pregnancies complicated by intrauterine growth restriction

INTRODUCTION: Pathomechanism of intrauterine growth restriction is a complex issue, involving many different factors, and is still undergoing an investigation. Improper placental angiogenesis, resulting in placental pathology, is considered to be one of the most important causes of IUGR. Placental vascular growth factors--placental growth factor (PIGF), vascular endothelial growth factor (VEGF) and its receptor (VEGFR-1), are involved in the mechanism of placental vascular development and maternal endothelial function during the pregnancy. AIM: The aim of our study was to evaluate the maternal serum concentration of vascular growth factors (PIGF, VEGF) and their receptor (VEGFR-1), as well as the placental volume in pregnancies complicated by IUGR, and to compare the results with healthy control groups. MATERIAL AND METHODS: 20 patients with intrauterine growth restriction and 18 healthy pregnant women were recruited. Their blood serum samples were assayed for the placental growth factor (PIGF), vascular endothelial growth factor (VEGF) and their receptor (VEGFR-1). These placental factors were measured with the ELISA- method (R@D Systems Kits. In all cases the placental volume was assessed with an ultrasound (Voluson V730 GE) with VOCAL (Virtual Organ Komputer-aided AnaLysis). RESULTS: Our investigation revealed significantly lower maternal serum concentrations of PIGF in pregnancies with IUGR, comparing to the controls in the third trimester. In most cases, VEGF concentrations were undetectable in the maternal serum both, in the second as well as in the third trimester. In the 2nd trimester VEGFR-1 concentrations were statistically higher in the investigated group. In the 3rd trimester the concentrations of VEGFR-1 were higher in the investigated group, but the difference has not achieved the level of statistical importance. The mean placental volume was lower in the investigated group but with not statistical gnificance. CONCLUSIONS: Presented and documented dependencies may indicate the involvement of angiogenic factors in a pathomechanism of intrauterine growth restriction process. It seems that the measurement of placental volume may be useful in IUGR diagnosis. However, it should be a complementary examination only, due to technical limitations.     

Ductus venosus Doppler measurement during labor

OBJECTIVES: To assess ductus venosus (DV) indices during the first stage of labor and the effect of ruptured membranes, meconium stained liquor and epidural analgesia (EDA). METHODS: Prospective cross-sectional study. Eighty-one women with low-risk singleton term pregnancies participated, 51 had normal labor (Group 1), and 30 experienced ruptured membranes and/or stained liquor (Group 2). Of the latter group 14 received EDA. The effect of various interventions and application of EDA on the ductus venosus index (DVI) and pulsatility index for veins (DV PIV) were tested. RESULTS: The feasibility rate was 94%. A significant increase of DV indices (DVI, DV PIV) was found in group 2 (P<0.001 and P<0.0005, respectively). The A-velocity was also significantly lower in group 2 (P<0.02). A markedly significant increase of DV indices (P<0.0001) among participants receiving EDA was observed in group 2. The mean+/-SD indices were: 0.53+/-0.10 for the DVI and 0.68+/-0.14 for the DV PIV in those women. There was a significant positive correlation of DV indices with the duration of amniorrhea in group 2 (PIV: r=0.66; P<0.002; DVI: r=0.68; P<0.001). CONCLUSIONS: Long-term amniorrhea seems to affect the fetal venous circulation reflected in increased DV waveform indices.     

Too old for IVF: are we discriminating against older women?

In vitro fertilization (IVF) in women of advanced age (>42 years) represents only 5%, a comparatively minute part, of the national IVF experience in the United States (US). In view of evolving population dynamics, it, however, also represents proportionally a rather quickly expanding patient need. Because of access restrictions at many IVF programs, this market does not live up to its potential. As best demonstrated by the 2004 US National Summary and Fertility Clinic Report, which for the first time reported pregnancies and births above age 45 year, IVF in women of advanced reproductive age represents a cutting edge area of interest for improving current IVF outcomes. Access to IVF should, therefore, not be withheld based on female age and/or baseline FSH levels. Instead, a definition of acceptable minimal pregnancy and life birth rates could be used to define the limits of offered access to IVF, independent of age and/or baseline FSH levels.