Genetic islands of <Emphasis Type="Italic">Streptococcus agalactiae</Emphasis> strains NEM316 and 2603VR and their presence in other Group B Streptococcal strains

Background  

Streptococcus agalactiae (Group B Streptococcus; GBS) is a major contributor to obstetric and neonatal bacterial sepsis. Serotype III strains cause the majority of late-onset sepsis and meningitis in babies, and thus appear to have an enhanced invasive capacity compared with the other serotypes that cause disease predominantly in immunocompromised pregnant women. We compared the serotype III and V whole genome sequences, strains NEM316 and 2603VR respectively, in an attempt to identify genetic attributes of strain NEM316 that might explain the propensity of strain NEM316 to cause late-onset disease in babies. Fourteen putative pathogenicity islands were described in the strain NEM316 whole genome sequence. Using PCR- and targeted microarray- strategies, the presence of these islands were assessed in a diverse strain collection including 18 colonizing isolates from healthy pregnant women, and 13 and 8 invasive isolates from infants with early- and late-onset sepsis, respectively.     

CHANGES IN CHEMICAL, SENSORY AND RHEOLOGICAL CHARACTERISTICS OF MANCHEGO CHEESES DURING RIPENING

Manchego cheese is a high-fat pressed ewe's-milk cheese made in Castilla-La Mancha (Spain) and produced by enzymatic coagulation. The minimum ripening time before marketing required by the Regulatory Board of the Manchego Cheese Appellation of Origin is 60 days.
This paper describes the physicochemical, proteolysis, sensory and texture characteristics of Manchego cheese, and the degree of homogeneity of cheeses made under the Manchego Appellation of Origin. The data gathered in this study indicate that sensory and instrumental analysis are useful tools for detecting changes in Manchego cheese during ripening. These changes were first detected by the instrumental analysis (2 months). The panelists detected differences after 4 months' ripening in all the factories. With physicochemical analysis, on the other hand, longer ripening times (6–8 months) are required before such changes become appreciated.     

Antibodies against modified low-density lipoproteins and their complexes in blood of patients with various manifestations of atherosclerosis

The study included 79 patients with coronary artery disease (CAD), 25 individuals with preclinical atherosclerosis and 59 healthy individuals. Key lipid parameters were examined in all the participants. Levels of antibodies (Abs) (IgG and IgM) against low density lipoproteins (LDL) modified by malondialdehyde (MDA), acetic anhydride and hypochlorite, were determined by the enzyme-linked immunosorbent assay (ELISA). Abs specificity was tested by competitive ELISA. Circulating immune complexes (CIC) were isolated by polyethylene glycol precipitation followed by determination of their cholesterol by the enzymatic method. Abs to hypochlorite-modified LDL (hypochlorite-LDL) detected in the serum samples did not demonstrate cross-reactivity with MDA-modified LDL (MDA-LDL) and acetylated LDL (acetyl-LDL). Patients with CAD had increased levels of CIC (p < 0.0001) and decreased levels of Abs (IgM) to hypochlorite- LDL, compared with healthy controls and patients with preclinical atherosclerosis (p = 0.006). A correlation between the levels of Abs (IgG) to the hypochlorite-LDL and Abs to MDA-LDL and acetyl-LDL was found. The content of the Abs (IgM) to MDA-LDL and acetyl-LDL correlated with CIC-cholesterol concentrations, while lipid parameters did not correlate with Abs levels.     

Effect of increased afterload on right ventricular function in newborn pigs

The effect of a progressive increase in right ventricular (RV) afterload was studied in pigs less than 24 h (group I) and 3-5 days old (group III). RV load was applied to increase mean pulmonary arterial pressure (Ppa) until right to left shunt was observed. Initially, pigs in group I had a significantly lower systemic arterial pressure (Psa = 63 +/- 2 vs. 82 +/- 5 mmHg) and higher Ppa (30 +/- 1 vs. 23 +/- 2 mmHg) even though the RV stroke work (RVSW) was similar (54.3 +/- 10.8 vs. 32.4 +/- 2.1 mmHg/ml) to group II. After a progressive rise in afterload, pigs in group I could maintain a higher RV stroke volume than those in group II (1.3 +/- 0.3 vs. 0.4 +/- 0.1 ml; P less than 0.05). At shunt condition, the RVSW was increased by 21 +/- 14% of the initial value in group I vs. a 32 +/- 8% decrease in group II (P less than 0.05). The ductus arteriosus was constricted and right-to-left shunt was observed in all animals at the foramen ovale level even though Ppa exceeded Psa before the rise in the right atrial pressure in group I. Thus, as RV afterload is increased in the pig, the older animals' right ventricle is progressively less capable of maintaining pulmonary blood flow than animals within 24 h of birth.     

Karyological studies in Sonchus section Muritimi (Asteraceae) from the Iberian Peninsula

MEJÍAS, J. A. & VALDÉS, B., 1988. Karyologiepl studies in Sonchus section Madtimi (Asteraceae) from the Iberian Peninmula. Karyological data support the distinction of S. aquatilis Pourret and S. maritimus L. at the specific level. Karyological data and hybridization experiments support the idea that S. × novocaslcllanus Cirujano has been produced by the hybridization of S. crassifolius Pourret ex Willd. and S. maritimus L.     

A bronchial epithelium-derived factor reduces pulmonary vascular tone in the newborn rat.

The factors accounting for the maintenance of a low pulmonary vascular resistance postnatally are not completely understood. The aim of this study was to test the hypothesis that bronchial epithelium produces a factor capable of relaxing adjacent pulmonary arterial smooth muscle. We studied fourth-generation intralobar pulmonary arteries and bronchi of 4- to 8-day-old rats. Arteries were mounted on a wire myograph, alone or with the adjacent bronchus. The presence of the attached bronchus significantly reduced pulmonary artery force generation induced by the thromboxane analog (U-46619) or KCl whether the endothelium was present or absent (P < 0.01). The converse was not true in that bronchial force generation was not affected when studied with the adjacent pulmonary artery. Mechanical removal of the bronchial epithelium or addition of the nitric oxide (NO) synthase (NOS) nonspecific (N(G)-monomethyl-l-arginine) or the specific neuronal NOS (7-nitroindazole) inhibitors increased arterial force generation to levels comparable to the isolated artery preparation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, significantly decreased (P < 0.01) NO release of pulmonary arteries only when the adjacent bronchus was present. We conclude that bronchial epithelium in the newborn rat produces a factor capable of lowering pulmonary vascular muscle tone. This relaxant effect can be suppressed by NOS and phosphatidylinositol 3-kinase kinase inhibition, suggesting an action via NOS phosphorylation and NO release. We speculate that such a mechanism may be operative in vivo and plays an important role in control of pulmonary vascular resistance in the early postnatal period.     

Targeting HER2: A report on the in vitro and in vivo pre-clinical data supporting trastuzumab as a radioimmunoconjugate for clinical trials

The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A″-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of ¹¹¹In-trastuzumab by melanoma (A375) s.c. xenografts and ¹¹¹In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected ¹¹¹In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of ¹¹¹In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected ¹¹¹In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama.Key words: monoclonal antibody, HER2, trastuzumab, radioimmunodiagnosis, radioimmunotherapy