Chronic gamma-irradiation results in increased cell killing and chromosomal aberration with specific breakpoints in fibroblast cell strains derived from non-Hodgkin's lymphoma patients.

Cultured skin fibroblast cells from 6 patients with non-Hodgkin's lymphoma (NHL) and 2 clinically normal subjects were compared for cell survival and chromosomal aberration after chronic gamma-irradiation. Fibroblasts from an ataxia telangiectasia (AT) homozygote and an AT heterozygote were used as positive controls. Following irradiation, fibroblasts from all 6 NHL patients showed an increase in both cell death and chromosomal aberration (breaks and rearrangements) compared to the normal subjects. The difference in the frequency of chromosomal aberration between the normals and the NHL patients remained virtually unchanged over a period of 24-72 h post irradiation incubation of the cells. Cell cycle analysis by flow cytometry carried out in 1 normal and 1 NHL fibroblast cell strain showed that more cells representing the NHL patient were in G2/M phase compared to the normal at various times of cytogenetic analysis. While the AT homozygote appeared to be the most radiosensitive, the AT heterozygote showed a slightly higher incidence of cell death and chromosomal aberration than the normals. The cellular and chromosomal radiosensitivity of fibroblast cell lines from the NHL patients differed slightly from that of the AT heterozygote but clearly occupied an intermediate position between the AT homozygote and the normal subjects. Cells from 3 of the NHL patients showed radiation-induced specific chromosomal breaks involving chromosomes 1, 2, 6, 8, 10 and 11 which correspond to known fragile sites. Such breakpoints associated with increased radiosensitivity may be indicative of predisposition to malignancy in the patients studied.     

Clinical data analysis of telmisartan for hypertension management in Indian population

It is of interest to evaluate the clinical characteristics, treatment patterns, clinical effectiveness, and safety of telmisartan as a monotherapy or as part of combination therapy in Indian adults (>18 years old) with hypertension. All patients were receiving telmisartan as monotherapy, or as a combination therapy for hypertension management. Demographics, risk factors, existing comorbidity, and ongoing medical therapies were retrieved from the patients’ medical records. A total of 8607 patients with hypertension (median age, 51.0 years) were part of the study. The gender distribution suggested, 5534(64.3%) patients were male, and 3073 (35.7%) were female patients. The excess salt intake (39.0%) was the most common risk factor according to the results. The analysis revealed telmisartan dual therapy (57.9%) as the most prescribed therapy, followed by monotherapy (32.5%), and triple therapy (9.6%). Further, telmisartan 40mg (21.3%) and telmisartan 40mg plus amlodipine 5mg (17.6%) were the most commonly prescribed therapies. The data suggested that only 17.2% of patients required dose titration. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHg) were significantly decreased with monotherapy (mean change: 19.8 [15.1] mmHg and 8.8[8.2] mmHg), dual therapy (mean change: 23.7 [16.6] mmHg and 10.3[8.5] mmHg), and triple therapy (mean change: 28.6 [19.0] mmHg and 12.1[10.8] mmHg) after the treatment (P<0.001). A total of 98.4% of the patients were compliant, and 97.6% achieved the target blood pressure goal with telmisartan-based therapy. There were 157 adverse events reported altogether. The Physicians'' global evaluation of efficacy and tolerability showed the majority of the patients receiving telmisartan-based therapy on a good to excellent scale. Telmisartan used as a monotherapeutic agent or as a part of combination therapy was successful and effective in reducing blood pressure and achieving the blood pressure target. Irrespective of the patient’s age, duration, and stages of hypertension, the study resulted in a good to excellent scale in efficacy and tolerability in the Indian patients having hypertension.     

Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study

Complement receptor type 2 (CR2, CD21) forms a tight complex with C3d, a fragment of C3, the major complement component. Previous crystal structures of the C3d-CR2 SCR 1-2 complex and free CR2 SCR 1-2 showed that the two SCR domains of CR2 form contact with each other in a closed V-shaped structure. SCR 1 and SCR 2 are connected by an unusually long eight-residue linker peptide. Medium-resolution solution structures for CR2 SCR 1-2, C3d, and their complex were determined by X-ray scattering and analytical ultracentrifugation. CR2 SCR 1-2 is monomeric. For CR2 SCR 1-2, its radius of gyration R(G) of 2.12(+/-0.05) nm, its maximum length of 10nm and its sedimentation coefficient s20,w(o) of 1.40(+/-0.03) S do not agree with those calculated from the crystal structures, and instead suggest an open structure. Computer modelling of the CR2 SCR1-2 solution structure was based on the structural randomisation of the eight-residue linker peptide joining SCR 1 and SCR 2 to give 9950 trial models. Comparisons with the X-ray scattering curve indicated that the most favoured arrangements for the two SCR domains corresponded to an open V-shaped structure with no contacts between the SCR domains. For C3d, X-ray scattering and sedimentation velocity experiments showed that it exists as a monomer-dimer equilibrium with a dissociation constant of 40 microM. The X-ray scattering curve for monomeric C3d gave an R(G) value of 1.95 nm, and this together with its s20,w(o) value of 3.17 S gave good agreement with the monomeric C3d crystal structure. Modelling of the C3d dimer gave good agreements with its scattering and ultracentrifugation parameters. For the complex, scattering and ultracentrifugation experiments showed that there was no dimerisation, indicating that the C3d dimerisation site was located close to the CR2 SCR 1-2 binding site. The R(G) value of 2.44(+/-0.1) nm, its length of 9 nm and its s20,w(o) value of 3.45(+/-0.01) S showed that its structure was not much more elongated than that of C3d. Calculations with 9950 models of CR2 SCR 1-2 bound to C3d through SCR 2 showed that SCR 1 formed an open V-shaped structure with SCR 2 and was capable of interacting with the surface of C3d. We conclude that the open V-shaped structures formed by CR2 SCR 1-2, both when free and when bound to C3d, are optimal for the formation of a tight two-domain interaction with its ligand C3d.     

Copper,selenium, and zinc concentrations in human milk during the first three weeks of lactation

Human milk samples were analyzed by neutron activation analysis (NAA) for three essential trace elements (Cu, Se, and Zn). Mothers' milk samples were collected from 25 lactating mothers from the Central Hospital, Tripoli, Libya. The average concentration level of Cu, Se, and Zn declined from 0.84 +/- 0.06 mg/L, 104 +/- 9.46 microg/L, and 16.1 +/- 2.67 mg/L at d 0 to 0.39 +/- 0.045 mg/L, 41.8 +/- 6.66 microg/L, and 4.95 +/- 1.3 mg/L, respectively, at d 20 of lactation. Copper and Zn levels in the Libyan mothers' milk were in agreement with reported levels from other countries, whereas Se was at a higher level. The Cu daily intake level is slightly higher than the RDA (Recommended Daily Allowance) value. Selenium and Zn have higher intake levels than the RDA values but within the tolerable upper intake levels.     

Induced changes in the proteomic profile of the phaeophyte Saccharina japonica upon colonization by the bryozoan Membranipora membranacea

The lacy crust bryozoan Membranipora membranacea frequently colonizes the late harvested blades of aquacultured Saccharina japonica. From proteomic profiles of S. japonica, 145 and 91 protein spots were detected from colonized and healthy tissues, respectively. Among them, 69 and 32 spots were significantly up- and downregulated, respectively, in expression level upon colonization. In M. membranacea colonized tissue, tripartite motif protein 2-like, microcompartments protein, carboxysome peptide shell peptide, trypsin precursor-like, transmembrane protein, two-component response regulator PilR, spermine/spermidine synthase, vanadium-dependent bromoperoxidase, peptide chain release factor 1, interaptin, 50S ribosomal protein L1P, plus agglutinin and leucine-rich repeat protein were upregulated, whereas protoporphyrinogen oxidase, PIH1 domain-containing protein 2, GTPase-activating protein alpha, cytoplasmic threonyl-tRNA synthetase, flavanone 3-hydroxylase, and eukaryotic translation initiation factor 3 proteins were downregulated. Moreover, DEAD/DEAH box helicase, glutamyl-tRNA reductase, and chaperone DnaJ protein were newly expressed in the colonized tissue. Most of the up- and downregulated proteins are known to be related to stress control, defense mechanisms, signal transduction, photosynthesis, protein metabolism, and the cytoskeleton.     

Induction of endothelial cell migration by proline analogs and its relevance to angiogenesis

The proline analogs cis-4-hydroxy-L-proline, 3,4-dehydro-L-proline, and 2-azetidinecarboxylic acid induced increases in the migration rate of retinal capillary endothelial cells, aortal endothelial cells, corneal endothelial cells, aortal smooth muscle cells, and retinal pericytes. cis-4-hydroxy-D-proline did not. The optimal concentration for migration induction by any of the active agents was approximately 10(-5) M. At higher concentrations (5 x 10(-4) M) migration was not induced or was inhibited. When tested by subcutaneous implant assays in rabbits, cis-4-hydroxy-L-proline and 2-azetidinecarboxylic acid consistently elicited a marked angiogenic response. Whereas these compounds are known to modulate collagen synthesis and secretion, the concentrations at which they are effective inducers of migration suggest that they may have a more specific target than general collagen synthesis.