scholarly journals Physiological and Clinical Significance of Disordered Cross-Linking of Fibrin

1977 ◽  
Author(s):  
L. Lorand

Disorders of fibrin stabilization are hemorrhagic conditions in which the patient’s plasma clot is lacking in inter-fibrin γ-glutamyl-ε-lysine isopeptide linkages. The primary defect occurs either because no fibrinoligase (FXIIIa) activity can be generated or because the enzyme cannot act on fibrin in the patient’s plasma. Distinction is made between hereditary disorders (Class I) and those appearing later in life because of an acquired inhibitor (Class II) directed against one of the steps on the pathway of fibrin stabilization: Of the genetic deficiencies (Class I), Type I is characterized by a lack of zymogen activity in plasma and Type II by the unreactivity of the cross-linking sites of the patient’s fibrin [“dysfibrin(ogen)emias”] towards fibrinoligase.There are three varieties of Class II abnormalities. In Type I, the acquired inhibitor interferes with zymogen activation. Type II inhibitors affect transamidation by competing against fibrin for the enzyme. The Type III inhibitor combines with fibrin rendering it unreactive towards fibrinoligase. The Type I and III inhibitors appear to be autoimmune antibodies.(Ann. N. Y. Acad. Sei., 202, 6, 1972).Differential diagnostic criteria for this family of molecular disorders will be discussed.

2019 ◽  
Vol 11 (2) ◽  
pp. 42-48
Author(s):  
Dr. Varsha Das ◽  
Dr. Vinaya .S. Pai ◽  
Dr. Siri Krishna ◽  
Dr. Shivaprasad Gaonkar ◽  
Dr. Gautham Kalladka ◽  
...  

This study was done to determine & correlate the lip print patterns in Skeletal Class I & Class II malocclusions. A sample of 160 individuals (80 skeletal Class I & 80 skeletal Class II malocclusion) aged 12 years and above, were selected for the study. A dark coloured lipstick was applied onto the cleaned & dried lips with a single stroke. A lip impression was made on a transparent cellophane tape strip which was removed & stuck to a white bond paper. Lip print patterns were analysed based on the Tsuchihashi classification i.e. Type I, Type I’, Type II, Type III, Type IV & Type V. The field of observation was confined to 10mm on either side of the quadrant from the midline and the pattern was resolved by counting highest number of lines in this area. Statistical analyses indicated that the prevalence of Type I & Type II lip pattern was significantly higher in Skeletal Class I & Class II malocclusion subjects respectively. The results showed a significant correlation between lip prints and skeletal sagittal malocclusion. Cheiloscopy can act as an early indicator of skeletal malocclusions, but further research is required for the evaluation of lip prints in a larger sample with distinctinherited malocclusions.


Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.


Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4213-4223 ◽  
Author(s):  
William K. Decker ◽  
Dongxia Xing ◽  
Sufang Li ◽  
Simon N. Robinson ◽  
Hong Yang ◽  
...  

Abstract In the control of T-helper type I (Th-1) polarization, dendritic cells (DCs) must interpret a complex array of stimuli, many of which are poorly understood. Here we demonstrate that Th-1 polarization is heavily influenced by DC-autonomous phenomena triggered by the loading of DCs with antigenically matched major histocompatibility complex (MHC) class I and class II determinants, that is, class I and II peptide epitopes exhibiting significant amino acid sequence overlap (such as would be physiologically present during infectious processes requiring Th-1 immunity for clearance). Data were derived from 13 independent antigenic models including whole-cell systems, single-protein systems, and 3 different pairs of overlapping class I and II binding epitopes. Once loaded with matched class I and II antigens, these “Th-1 DCs” exhibited differential cytokine secretion and surface marker expression, a distinct transcriptional signature, and acquired the ability to enhance generation of CD8+ T lymphocytes. Mechanistically, tRNA-synthetases were implicated as components of a putative sensor complex involved in the comparison of class I and II epitopes. These data provide rigorous conceptual explanations for the process of Th-1 polarization and the antigenic specificity of cognate T-cell help, enhance the understanding of Th-1 responses, and should contribute to the formulation of more effective vaccination strategies.


1992 ◽  
Vol 176 (1) ◽  
pp. 119-128 ◽  
Author(s):  
R S van Binnendijk ◽  
C A van Baalen ◽  
M C Poelen ◽  
P de Vries ◽  
J Boes ◽  
...  

The routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein (F) of measles virus (MV) to HLA class I and class II presentable peptides have been examined, using cloned cytotoxic T lymphocytes in functional assays. Presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines was achieved using live virus, ultraviolet light-inactivated virus, and purified MV-F delivered either as such or incorporated in immunostimulating complexes (MV-F-ISCOM). Only live virus and MV-F-ISCOM allow presentation by class I molecules, while all antigen preparations permit class II-restricted presentation. We observe presentation of MV-F from live virus and as MV-F-ISCOM by class II molecules in a fashion that is not perturbed by chloroquine. Our studies visualize novel presentation pathways of type I transmembrane proteins.


Author(s):  
Jui-Teng Lin

Aims: To resolve the controversial issues of UV-light-initiated corneal collagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. Study Design:  Analysis and measured data of CXL. Place and Duration of Study: New Vision Inc, Taipei, between June 2021 and August 2021. Methodology: The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen and riboflavin concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), the riboflavin concentration, diffusion and drops pre-operation and interoperation administration, the concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square root of light intensity, and light dose, respectively. Conclusion: The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.


1987 ◽  
Vol 105 (4) ◽  
pp. 1873-1884 ◽  
Author(s):  
E A Wayner ◽  
W G Carter

Using monoclonal antibody technology and affinity chromatography we have identified four distinct classes of cell surface receptors for native collagen on a cultured human fibrosarcoma cell line, HT-1080. Two classes of monoclonal antibodies prepared against HT-1080 cells inhibited adhesion to extracellular matrix components. Class I antibodies inhibited cell adhesion to collagen, fibronectin, and laminin. These antibodies immunoprecipitated two noncovalently linked proteins (subunits) with molecular masses of 147 and 125 kD, termed alpha and beta, respectively. Class II antibodies inhibited cell adhesion to native collagen only and not fibronectin or laminin. Class II antibodies immunoprecipitated a single cell surface protein containing two noncovalently linked subunits with molecular masses of 145 and 125 kD, termed alpha and beta, respectively. The two classes of antibodies did not cross-react with the same cell surface protein and recognized epitopes present on the alpha subunits. Pulse-chase labeling studies with [35S]methionine indicated that neither class I nor II antigen was a metabolic precursor of the other. Comparison of the alpha and beta subunits of the class I and II antigens by peptide mapping indicated that the beta subunits were identical while the alpha subunits were distinct. In affinity chromatography experiments HT-1080 cells were extracted with Triton X-100 or octylglucoside detergents and chromatographed on insoluble fibronectin or native type I or VI collagens. A single membrane protein with the biochemical characteristics of the class I antigen was isolated on fibronectin-Sepharose and could be immunoprecipitated with the class I monoclonal antibody. The class I antigen also specifically bound to type I and VI collagens, consistent with the observation that the class I antibodies inhibit cell adhesion to types VI and I collagen and fibronectin. The class II antigen, however, did not bind to collagen (or fibronectin) even though class II monoclonal antibodies completely inhibited adhesion of HT-1080 cells to types I and III-VI collagen. The class I beta and II beta subunits were structurally related to the beta subunit of the fibronectin receptor described by others. However, none of these receptors shared the same alpha subunits. Additional membrane glycoprotein(s) with molecular mass ranges of 80-90 and 35-45 kD, termed the class III and IV receptors, respectively, bound to types I and VI collagen but not to fibronectin. Monoclonal antibodies prepared against the class III receptor had no consistent effect on cell attachment or spreading, suggesting that it is not directly involved in adhesion to collagen-coated substrates.(ABSTRACT TRUNCATED AT 400 WORDS)


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