scholarly journals A model for calculating beta exposure doses to tracheobronchial cells during movement of a point source

2021 ◽  
Vol 14 (3) ◽  
pp. 6-17
Author(s):  
V. S. Repin
Keyword(s):  
Point Source ◽  
Single Point ◽  
Dose Calculation ◽  
Tracheobronchial Tree ◽  
Beta Particle ◽  
Basal Cells ◽  
Generation Number ◽  
Bronchial Lumen

The article describes a model and method for calculating beta-exposure doses to secretory and basal cells of the tracheobronchial part of the respiratory tract when a point source of 1 Bq activity moves along the inner surface of respiratory formations. The calculations, that used for proposed model, were performed by using a 90Y point source as an example. The dose calculation model takes into account the speed o f movement of the radiation source in each respiratory formation, the size of the respiratory formations, and the depth of the secretory and basal cells. The dose calculation is based on  the dose rate attenuation functions published by W. G. Cross et al.  (DOI: 10.1097/00004032-199208000-00002). The calculations were performed for a cylindrical model of a respiratory formation. Two kinds of cells were considered for the dose estimation: cells irradiated without beta-particle exit into bronchial lumen (type 1 cells) and cells irradiated due to beta-par­ticle exit into bronchial lumen (type 2 cells). The results of calculations showed, that as far as the generation number increasing, the average irradiation doses of the type 1 cells are 10 or more times greater than those of the type 2 cells. With increasing generation number in the tracheobronchial tree, doses per cells increase by several orders of magnitude. The highest doses are formed in bronchioles of generations 9-15, reaching units and tens of mGy. In spite of the fact that the number of generation increases, the total number of irradiated cells decreases, the collective doses of irradiated cells (sum of doses to all cells of the respiratory formation) in the last generations are 30-50 times higher than the doses of the first generations. Thus, in case of a single point source, there is a significant (by many orders of magnitude) scatter of doses to individual cells in indi­vidual respiratory formation, as well as significant differences in average doses of trachea, individual bronchi and bronchioles.

Differential expression of plasminogen activators and their inhibitors in an organotypic skin coculture system

1993 ◽  
Vol 106 (1) ◽  
pp. 45-53 ◽  
Author(s):  
C.S. Chen ◽  
B. Lyons-Giordano ◽  
G.S. Lazarus ◽  
P.J. Jensen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Urokinase Plasminogen Activator ◽  
Basal Cells ◽  
Type Plasminogen Activator ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

Using immunohistochemistry and in situ hybridization, we have characterized the expression and localization of components of the plasminogen activator proteolytic cascade in an organotypic coculture system which consists of a “dermal” portion (human dermal fibroblasts throughout a collagen matrix) and a stratified, well-differentiated epidermal portion. Specifically, the following components were examined: the enzymes urokinase-type plasminogen activator and tissue-type plasminogen activator and their type 1 and type 2 inhibitors. Urokinase plasminogen activator mRNA and antigen were found predominantly in the least differentiated, basal keratinocytes; in some fields there was also faint deposition of antigen beneath the basal cells. The distribution of plasminogen activator inhibitor type 1 was similar to that of urokinase, except that inhibitor type 1 antigen deposition beneath the basal cells appeared more intense and uniform. In contrast to the results with urokinase plasminogen activator and inhibitor type 1, tissue plasminogen activator mRNA and antigen were localized focally in the suprabasal, i.e. more differentiated, keratinocytes. Plasminogen activator inhibitor type 2 mRNA and antigen were detected in most epidermal layers, but were more intense suprabasally and often spared the basal layer. These studies demonstrate that the same type of cell, i.e. the keratinocyte, can express different components of the plasminogen activator cascade depending on its state of differentiation. The change in expression of plasminogen activator cascade components with keratinocyte differentiation suggests distinct epidermal functions for these components, related to cell-matrix interaction and epidermal differentiation.

Effects of Single Point Mutations within Proposed Copper Binding Sites on Specific Activity and Inter-Chain Affinity of Factor VIII.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1730-1730
Author(s):  
Hironao Wakabayashi ◽  
Qian Zhou ◽  
Keiji Nogami ◽  
Philip J. Fay
Keyword(s):  
Factor Viii ◽  
Binding Sites ◽  
Specific Activity ◽  
Single Point ◽  
Point Mutations ◽  
High Affinity ◽  
Kd Values ◽  
Single Point Mutations

Abstract Copper ions appear important for the structural integrity and the function of factor VIII. Reconstitution studies have shown that Cu2+ increases specific activity of factor VIII as well as increases affinity between heavy chain (HC) and light chain (LC). Based on the ceruloplasmin homology, the existence of three Cu2+ binding sites has been proposed. These include a type 1 site in HC (A1 domain) coordinated by C310, H315, H267, and M320, a type 1 site in LC (A3 domain) coordinated by C2000, H1954, H2005, and M2010, and type 2 site spanning A1 and A3 domains coordinated by H99 and H1957 with possible other additional residues. We rationalized that point mutations within a putative Cu2+ coordination sites would diminish Cu2+ binding at that site, as detected by changes in factor VIII specific activity and/or inter-subunit affinity. We produced several mutant factor VIII proteins bearing point mutation of C310S, H315A, C2000S, H1954A, H99A, or H1957A using a B-domainless human factor VIII vector. Each mutant was stably expressed and purified by SP-sepharose, which bound factor VIII primarily though LC. Western blotting indicated a reduction in the relative amount of HC in C310S and H99A factor VIII forms, suggesting that inter-chain affinity was reduced by these mutations. EDTA-treated factor VIII forms in the presence of Ca2+ were titrated with Cu2+ and activity was monitored using a factor Xa generation assay. The concentration of free Cu2+ was controlled by the presence of EDTA and Ca2+ based on the known values for Cu2+-EDTA and Ca2+-EDTA affinities. The activity regain observed for wild type factor VIII following titration with Cu2+ yielded a Kd = 11.5 ± 2.2 fM. All of the mutants tested retained a high affinity response to Cu2+, suggesting that single point mutations were not sufficient to eliminate Cu2+ binding. However, while Kd values for H1957A (10.3 ± 2.2 fM), H99A (2.1 ± 1.9 fM), H315A (6.7 ± 3.1 fM), and C310S (12.7 ± 3.4 fM) retained similar or slightly reduced affinity for Cu2+, the Kd values for C2000S (304 ± 105 fM) and H1954A (365 ± 105 fM) showed a significant reduction in Cu2+ affinity. When factor VIIIa subunits were titrated with Cu2+ and monitored by intrinsic fluorescence, only purified A1 subunit showed a saturable effect of the signal (Kd = 11.9 ± 4.9 fM), indicating that this subunit contained a high affinity Cu2+ binding site. Taken together, these results suggest that occupancy of the type 1 Cu2+ binding site in A3 contributes to the Cu2+-dependent increase in specific activity of factor VIII and that the type 1 site in A1 and/or the type 2 site contributes to HC-LC association.

Type 2 Diabetes Overtakes Type 1 in Hispanic Girls

2008 ◽  
Vol 38 (15) ◽  
pp. 18
Author(s):  
SHERRY BOSCHERT
Keyword(s):  
Type 2 Diabetes

Molecular analysis of FVIII gene in severe HA patients of Costa Rica

2010 ◽  
Vol 30 (S 01) ◽  
pp. S150-S152
Author(s):  
G. Jiménez-Cruz ◽  
M. Mendez ◽  
P. Chaverri ◽  
P. Alvarado ◽  
W. Schröder ◽  
...  
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Costa Rican ◽  
Factor Viii Gene ◽  
Intron 22 Inversion ◽  
Intron 1 ◽  
Polymerase Chain ◽  
Inversion Analysis

SummaryHaemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. Patients, methods: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. Results: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. Discussion: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.

Polymorphisms of the Plasminogen Activator Inhibitor- 1 Gene in Type 1 and Type 2 Diabetes, and in Patients with Diabetic Retinopathy

1994 ◽  
Vol 71 (06) ◽  
pp. 731-736 ◽  
Author(s):  
M W Mansfield ◽  
M H Stickland ◽  
A M Carter ◽  
P J Grant
Keyword(s):  
Diabetic Retinopathy ◽  
Plasminogen Activator Inhibitor ◽  
Allelic Frequency ◽  
Repeat Sequence ◽  
Dinucleotide Repeat ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Difference ◽  
Pai 1

SummaryTo identify whether genotype contributes to the difference in PAI-1 levels in type 1 and type 2 diabetic subjects and whether genotype relates to the development of retinopathy, a Hind III restriction fragment length polymorphism and two dinucleotide repeat polymorphisms were studied. In 519 Caucasian diabetic subjects (192 type 1, 327 type 2) and 123 Caucasian control subjects there were no differences in the frequency of the Hind III restriction alleles (type 1 vs type 2 vs control: allele 1 0.397 vs 0.420 vs 0.448; allele 2 0.603 vs 0.580 vs 0.552) nor in the allelic frequency at either dinucleotide repeat sequence. In 86 subjects with no retinopathy at 15 years or more from diagnosis of diabetes and 190 subjects with diabetic retinopathy there was no difference in the frequency of Hind III restriction alleles (retinopathy present vs retinopathy absent: allele 1 0.400 vs 0.467; allele 2 0.600 vs 0.533) nor in the allelic frequencies at either dinucleotide repeat sequence. The results indicate that there is no or minimal influence of the PAI-1 gene on either PAI-1 levels or the development of diabetic retinopathy in patients with diabetes mellitus.

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