Search PubMed⌕ Search

Biomedical subjects

C Bloch

Publications and source records attributed to C Bloch.

At least 37 records · Page 2Linked to original sources

Functional and structural features of gamma-zeathionins, a new class of sodium channel blockers.

Gamma1- and gamma2-zeathionins (gamma1-Z and gamma2-Z) are members of a family of small and basic peptides involved in plant protection. These plant defensins exhibit remarkable structural similarity to scorpion neurotoxins and insect defensins. In the present report, we used the whole-cell patch clamp technique to investigate the inhibition of the sodium current (I(Na)) by gamma1-Z and gamma2-Z in the GH3 cell line. Both gamma1-Z and gamma2-Z rapidly and reversibly inhibited I(Na) without changing the kinetics or voltage dependence of activation or inactivation. To our knowledge, this is the first example of a plant protein that inhibits the sodium channel. From structural comparisons with the mu-conotoxins, a family of peptides that block the sodium channel, we detected some similar features that could provide the basis of inhibition of sodium channels by gamma-zeathionins.

Amino Acid Sequence↗

1H NMR structure of an antifungal gamma-thionin protein SIalpha1: similarity to scorpion toxins.

The three-dimensional structure of the Sorghum bicolor seed protein gamma-thionin SIalpha1 has been determined by 2D 1H nuclear magnetic resonance (NMR) spectroscopy. The secondary structure of this 47-residue antifungal protein with four disulphide bridges consists of a three-stranded antiparallel sheet and one helix. The helix is tethered to the sheet by two disulphide bridges which link two successive turns of the helix to alternate residues i, i+2 in one strand. Possible binding sites for antifungal activity are discussed. The same fold has been observed previously in several scorpion toxins.

Amino Acid Sequence↗

Evidence for a role of delayed death and genomic instability in radiation-induced neoplastic transformation of human hybrid cells.

HeLa x skin fibroblast human hybrid cells have been developed into a model of radiation-induced neoplastic transformation. The authors' studies indicate that the loss of putative tumour suppressor loci on fibroblast chromosomes 11 and 14 is evident after radiation-induced neoplastic transformation. How these fibroblast chromosomes/putative tumour suppressor loci are lost after radiation exposure is currently being investigated. It has been shown that the appearance of transformed foci correlates with the onset of the delayed reduction in plating efficiency or delayed death. This delayed death appears to be the result of the onset of a novel delayed apoptosis in the irradiated progeny beginning around day 8 post-irradiation. It was proposed that the reduction in plating efficiency and subsequent neoplastic transformation are all the result of a radiation-induced genomic instability. The instability process has two relevant outcomes: (1) cell death due to the induction of a delayed apoptosis in cells; and (2) neoplastic transformation of a small subset of survivors that have lost fibroblast chromosomes 11 and 14 (tumour suppressor loci) but either have not acquired enough genetic damage to induce the apoptotic response or have undergone molecular changes allowing them to bypass apoptosis. Data from the genomic instability and delayed death literature will be reviewed in terms of relevance to radiation-induced neoplastic transformation. New data are presented which demonstrate that use of growth media supplemented with a specific lot of calf serum was found to increase the number of cells undergoing radiation-induced neoplastic transformation, compared with standard serum after a fixed dose of radiation. This correlates with an increase in delayed death in the irradiated progeny which the authors propose is the result of increased genomic instability post-irradiation of cells grown in this serum. Preliminary data are presented indicating that a delayed apoptosis is also seen after high-energy He- particle exposure in this system.

Alpha Particles↗

Phantom assessment of lung dose from proton arc therapy.

PURPOSE: To compare resultant lung dose from proton arc therapy of the chest wall to that from electron arc therapy. METHODS AND MATERIALS: A 200 MeV proton beam from the Indiana University Cyclotron was range shifted and modulated to provide a spread out Bragg peak extending from the surface to a depth of 4 cm in water. The chest wall of an Alderson Rando phantom was irradiated by this beam, collimated to a 20 x 4 cm field size, while it rotated on a platform at approximately 1 rpm. For comparison, electron arc therapy of the Rando phantom chest wall was similarly performed with 12 MeV electrons and the resultant lung dose measured in each case. RESULTS: Dose-volume histograms for the Rando phantom left lung indicate a reduced volume of irradiated lung for protons at all dose levels and an integral lung dose that is half that for electron arc therapy in the case studied. In addition, a more uniform dose coverage of the target volume was achieved with the proton therapy. CONCLUSION: This study demonstrates a potential role for proton arc therapy as an alternative to electron arc therapy when lung dose must be minimized.

Calibration↗

Discovery of disseminated J96-like strains of uropathogenic Escherichia coli O4:H5 containing genes for both PapG(J96) (class I) and PrsG(J96) (class III) Gal(alpha1-4)Gal-binding adhesins.

The pyelonephritis-associated adhesin gene papG of Escherichia coli occurs in three variants. Whereas the class II and class III variants are common among human urinary tract infection isolates, the class I allele, despite being the first cloned, has previously been found only in source strain J96. Five strains have been discovered from geographically diverse locales that, like J96, contain both the class I and class III papG alleles. One strain caused bacteremia, whereas 4 caused cystitis. Like J96, all 5 had group III capsule genes, expressed the H5 flagellar antigen and the F13 fimbrial antigen, and exhibited similar genomic patterns and virulence factor profiles. These findings demonstrate that the class I papG allele is not unique to J96 but is present in a group of extraintestinal isolates of E. coli O4:H5 that represent a disseminated virulent clonal group.

Adhesins, Escherichia coli↗

Bcl-xS enhances adenoviral vector-induced apoptosis in neuroblastoma cells.

bcl-x is a member of the bcl-2 family of genes and by alternative splicing gives rise to two distinct mRNAs: bcl-xL and bcl-xS. We have previously investigated the expression of Bcl-x in neuroblastoma (NB) cell lines and have shown that Bcl-xL is expressed and functions to inhibit chemotherapy-induced apoptosis. However, none of the NB cell lines expressed Bcl-xS. The aim of the present study was to determine the effects of Bcl-xS expression on the viability of NB cells. A panel of NB cell lines (CHP-382, GOTO, SHEP-1, SHSY-5Y, and GI-CA-N) were infected with either a bcl-xS adenovirus (pAdRSV-bcl-xS) or a control virus (pAdRSV-lac-z). NB cells showed loss of viability with both viruses, although the bcl-xS virus was most toxic. Importantly, infection with the bcl-xS adenovirus resulted in rapid loss of cell viability, DNA fragmentation, and morphological features of apoptosis even in NB cells transfected to overexpress Bcl-2 and Bcl-xL. These findings suggest that deregulated expression of Bcl-xS using an adenovirus may provide a novel mechanism for initiating cell death in tumors that express Bcl-2 or Bcl-xL.

Adenoviridae↗

Amino acid sequence of the Phaseolus vulgaris var. "fogo na serra" inhibitor and interactive surface modeling for the enzyme-inhibitor complex.

A trypsin and chymotrypsin inhibitor from seeds of Phaseolus vulgaris var. "Fogo na Serra" (PFSI) was purified and its complete amino acid sequence was determined using Edman degradation methods. The inhibitor was found to belong to the Bowman-Birk family of enzymatic inhibitors; it has 82 amino acid residues and a 8.985-kDa molecular mass. The PFSI/alpha-chymotrypsin binary complex has been modeled using the Turkey ovomucoid inhibitor third domain (OMTKY3) bound to alpha-chymotrypsin [Fujinaga et al. (1987), J. Mol. Biol., 195, 397-418. template. The model allowed identification of the binding surface.

Amino Acid Sequence↗

Amino acid sequence and disulphide-bridge pattern of three gamma-thionins from Sorghum bicolor.

The complete primary structure of a new alpha-amylase inhibitor from Sorghum bicolor belonging to the gamma-thionin family has been determined and the amino acid sequences of two components of the family already elucidated have been corrected by combining the classical Edman degradation with advanced mass spectrometric procedures. The same integrated approach allowed us to define the pattern of the disulphide bridges in the three isoinhibitors. The arrangement of the cysteine pairing was determined as Cys3-Cys47, Cys14-Cys34, Cys20-Cys41 and Cys24-Cys43. The amino acid sequences of the alpha-amylase inhibitors share a high degree of similarity with the related plant gamma-thionins. All these proteins consist of 47 residues, contain eight cysteine residues forming four disulphide bridges, and show the presence of two clusters of basic amino acids located at both ends of the polypeptide chain. The pattern of S-S bridges determined for the isoinhibitors is identical to that inferred by NMR analysis in two related gamma-thionins, thus suggesting a highly conserved organization of the disulphide pairing. These results indicate that the structural similarities among the different gamma-thionins extend far beyond the primary structure and possibly concern the secondary structure and the general folding of the entire gamma-thionin family.

Amino Acid Sequence↗

Virulence characteristics of Escherichia coli causing first urinary tract infection predict risk of second infection.

Escherichia coli causes most urinary tract infections (UTIs) in ambulatory populations. Several bacterial virulence factors occur more frequently among urinary E. coli isolates than among fecal isolates, but none have been reported to predict risk of second UTIs. DNA hybridization was used to characterize the bacterial virulence profiles of urinary E. coli isolates from 174 women with first UTI and compared for risk of second UTI. Of the women, 28 (16%) had a culture-confirmed second UTI within 6 months of a negative test-of-cure. Three virulence factors were associated with a significantly lower risk of second UTI: cytotoxic necrotizing factor (relative risk [RR] = 0.0; 95% confidence interval [CI], 0.0, 0.42); hemolysin (RR, 0.10; 95% CI, 0.01, 0.69), and S fimbrial adhesin (RR, 0.25; 95% CI, 0.06, 1.00). Dr binding was associated with a 2-fold increased risk of second UTI (RR, 2.30; 95% CI, 1.23, 4.29). Half of all paired first and second UTI isolates from the same subject were apparently the same.

Adult↗

Comparative Ngas measurements for a parallel plate chamber in proton, electron, and 60Co beams.

The TG21 protocol introduced the Ngas calibration method for parallel plate chambers in high-energy electron beams. This calibration method was performed for a Markus parallel plate chamber in proton and electron beams of various energies as well as a 60Co beam. For an individual chamber, the Ngas value in proton beams differs from the Ngas value in cobalt and electron beams by the ratio of (W/e) for proton beams to that of a 60Co beam. While the replacement correction factor is essential for Markus chambers in low-energy electron beams, the results of our Nppgas measurements in proton beams showed that the Markus chamber does not need a replacement correction factor for therapeutic proton beams of energy 20-170 MeV. These results indicate that the 0.7-mm guard ring of the Markus chamber is adequate to prevent the in-scattering of secondary electrons produced by proton irradiation of the chamber wall or medium.

Biophysical Phenomena↗