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Identification of mRNA coding for factor VII protein in human alveolar macrophages--coagulant expression may be limited due to deficient postribosomal processing.

Clotting factors synthesized by monocytes and macrophages may initiate coagulation reactions during inflammation. Functional vitamin K-dependent coagulation factors have been found to be associated with human monocytes/macrophages, but there are no reports identifying mRNA coding for vitamin K-dependent proteins in these cells. In the present studies, factor VII mRNA was found in total RNA extracted from freshly isolated human alveolar macrophages using hybridization with a complementary DNA probe. On the other hand, vitamin K-dependent carboxylase activity which is required for postribosomal modification of the protein, was not detectable in the macrophages before or after culture, and human blood mononuclear leukocytes also lacked this enzyme activity. Control human and rat hepatoma cells exhibited high levels of carboxylase activity within the same experiments. Using sensitive kinetic assays, no increase in factor VII activity was detected during culture of alveolar macrophages under conditions promoting 1.78 +/- .24 (n = 8) fold increases of tissue factor activity. These findings with freshly isolated cells demonstrate that alveolar macrophages synthesize factor VII mRNA in vivo. However, the mRNA was found in the absence of evidence for gamma-carboxylase activity or processing of the factor into a functional clotting enzyme. The results imply that functional expression of any synthesized coagulation factor VII in alveolar macrophages may be limited or prevented due to a cellular deficiency at the level of postribosomal processing.

Carbon-Carbon Ligases

Antigen processing and presentation in vivo: the microenvironment as a crucial factor.

Antigen processing and presentation in vitro is an increasingly well understood phenomenon. However, in vivo, a large number of variables conspire to obscure and confuse. In this article, Nico van Rooijen attempts to bring order to events that occur in the spleen after antigenic challenge: starting with the large body of reliable in vitro data he incorporates information on splenic anatomy, cell trafficking and the cellular microenvironment to arrive at a physiological model for antigen handling in vivo.

Animals

[A factor influencing the process of chromatin condensation in hepatocytes of regenerating rat liver].

It was shown with the model supramolecular chromatin systems that the activity of the factor of chromatin condensation changes in the process of liver regeneration. No activity of the factor of chromatin condensation was found 20 hrs after operation. Within 32-33 hrs (in the period of increased mitotic frequency) its activity approaches that prior to the operation. The nature of the activity of the factor of chromatin condensation is discussed with respect to the functional state of chromatin.

Animals

Identification of a peptidase which processes atrial natriuretic factor precursor to its active form with 28 amino acid residues in particulate fractions of rat atrial homogenate.

With the objective of identifying specific peptidase responsible for the processing of atrial natriuretic factor precursor pro-ANF to the circulating active form ANF (99-126), a fluorometric assay method was devised using synthetic fluorogenic substrate Boc-Ala-Gly-Pro-Arg-MCA(methylcoumarinamide) which contains the amino acid sequence immediately adjacent to the arginyl peptide bond which is cleaved in the natural processing of pro-ANF. A protease which selectively cleaves this bond and produces the natural circulating peptide was identified in the particulate fraction of rat atrial homogenate and was solubilized by 1.6 M KCl. It was partially purified by affinity chromatography heparin-agarose column and was shown to be a serine protease. Its reaction product with natural pro-ANF was identified as ANF (99-126) containing 28 amino acid residues.

Animals

[Effects of acyclic analogs of atrial natriuretic factor on proliferative processes of the epithelial tissue in white rats].

The effect of atrial natriuretic factor (ANF) synthetic linear truncated analogues AP-H-6-OH and AP-FOR-6-OH on corneal, skin, duodenum and colon epithelium proliferation has been studied on male rats. The epithelium mitotic activity and DNA synthesis were evaluated 4 and 24 h after intraperitoneal injection of 10 or 100 micrograms/kg peptides. In a dose of 10 micrograms/kg both ANF synthetic analogues inhibited proliferation processes in corneal epithelium, but activated the DNA synthesis in duodenum and colon epithelium. AP-FOR-6-OH (10 micrograms/kg) decreased the mitotic activity of skin epithelium and increased the silver grain density over the cell nuclei at the same time. 100 micrograms/kg ANF analogues stimulated cell mitogenesis in all organs studied. According to the data obtained ANF linear truncated analogues influence on epithelium proliferation is similar to effector of previously studied cyclic atriopeptin AP II.

Animals

[Rabies prognosis in western Siberia and the regulatory factors of the epizootic process].

In this article the regulatory factors of the epizootic process are considered and the spatial-temporal prognostication of rabies infection in the region is proposed on the basis of data on rabies morbidity among animals, the purchase of skins of carnivorous animals for 20-25 years, virological experiments on wild animals, calculation of the number of carnivores and small mammals, as meteorological observations. The study has shown that a variety of animal species serving as hosts for the virus and its population differences contribute to the stable existence of the infection. Rabies morbidity has been found to be positively linked with its preceding level, the number of wild animals, the height and hardness of the snow cover and negatively with the number of small mammals.

Animals

The aging process: major risk factor for disease and death.

Aging is the accumulation of changes responsible for the sequential alterations that accompany advancing age and the associated progressive increases in the chance of disease and death. Average life expectancies at birth in the developed countries are now approaching plateau values as the aging changes associated with the environment and disease near irreducible levels. The inborn aging process is now the major risk factor for disease and death after around age 28 in the developed countries and limits average life expectancy at birth to approximately 85 years. Future significant increases in average life expectancy--a rough measure of the healthy, productive life-span, i.e., the functional life-span--in these countries will be achieved only by slowing the rate of production of aging changes by the aging process. Many theories have been advanced to account for the aging process. The free radical theory of aging is discussed briefly. The importance attached to increasing the functional life-span dictates that aging hypotheses be explored for practical means of achieving this goal while work continues toward a consensus on the cause(s) of the aging process. Efforts to further increase the functional life-span by conventional measures are now almost futile, whereas those directed toward slowing the aging process are just beginning. These new efforts show promise.

Aging

[The importance of risk factors in cerebrovascular processes while taking oral contraceptives (author's transl)].

21 young female and 15 young male patients with cerebrovascular insults were examined for risk factors. 14 of the 15 male patients showed clear cut risk factors: obesity, diabetes, hyperlipidemia, arterial hypertension, smoking, thromboses, vitium cordis. 20 of the 21 female patients took oral contraceptives. 60% of the female patients with angiographically confirmed stenoses and occlusion did not show any other risk factor. These results support the hypothesis that oral contraceptives are in themselves a risk factor.

Adult

Psychosomatic factors in the process of cancerogenesis. Theoretical models and empirical results.

The core of the authors' research program consists in the assumption that complex statistical interactions of sociological and psychological factors with pathophysiological and standard risk factors are more important for the early detection, prediction and prevention of cancer than one or just a few medical risk factors, e.g. the relationship between smoking and lung cancer. As the analysis of these relationships can only be done in interdisciplinary research, interpretation and discussion of social scientific, molecular biological and epidemiological aspects was attempted. In the first part we explicate a model of relevant propositions from the psychosomatic literature to explain the relationship between psychosocial factors of carcinogenesis. A discussion of the authors' research program contains additional variables and propositions. It appears to the authors that among the psychosocial and sociological factors of carcinogenesis, the molecular biological variables are especially relevant, as they form the intervening link between the social science variables and cancer. Discussion of the methodology and the sampling of the authors' empirical studies follows. Two prospective studies, carried out in Yugoslavia and West Germany, are described in detail. The data of these studies are used in the empirical analysis. In the next part the empirical results of different multivariate analyses are presented: The effects of the sociological and psychological variables on carcinogenesis are described; standard risk factors and biochemical-molecular biological factors are brought together, special attention being given to the interaction between these two groups of variables.

Adult

The manufacturing process of recombinant factor VIII, recombinate.

In summary, this brief report documents the cell culture and rAHF purification systems used to produce rFVIII and has focused on the unique characteristics of the cell line, the production process, and purification system used. This review emphasizes the general philosophy used throughout the research and development of this innovative and complex therapeutic agent, in order to provide a safe and efficacious rAHF in the management of individuals with hemophilia A. This review provides a brief description of the in-process system and controls that have been incorporated to meet the high standards and safety objective.

Animals

Comparison of the cross-linking patterns of lamprey fibrinogen and fibrin by the action of the intrinsic lamprey factor XIII and human factor XIII during the process of blood coagulation.

Intrinsic lamprey factor XIII cross-links the gamma chain of lamprey fibrin (50,000 daltons) to the gamma-dimer (100,000 daltons). The alpha-chain (110,000 daltons) is cross-linked very slowly to alpha-dimer (210,000 daltons) and alpha-trimer (330,000 daltons). In contrast, human factor XIII, when added in combination with intrinsic lamprey factor XIII, cross-links the alpha-chain of lamprey fibrin to a high molecular weight polymer, and any remaining gamma-chain is also cross-linked to a polymer. However, the gamma-chain that has previously cross-linked to the gamma-dimer by the intrinsic lamprey factor XIII remains as a gamma-dimer. Factor XIII-free lamprey fibrin cross-links all its subunits (alpha, beta, gamma) to high molecular weight polymers when human factor XIII is added. In contrast to human and bovine fibrin where alpha-chain cross-linking in the process of blood coagulation commences when all of the gamma-chain has cross-linked, the lamprey alpha-chain will begin to cross-link when approximately half of the gamma-chain has cross-linked to the gamma-dimer.

Animals

Disruption of intracellular processing of epidermal growth factor by methylamine inhibits epidermal growth factor-induced DNA synthesis but not early morphological or transcriptional events.

Upon internalization, epidermal growth factor (EGF) is proteolytically processed from its COOH terminus as it traverses intracellular vesicles and lysosomes. This report describes experiments which were conducted to determine whether lysosomotropic amines such as methylamine, which are known to inhibit degradation of EGF, are able to significantly inhibit the COOH-terminal processing of EGF, and whether disruption of EGF processing would negatively affect EGF-stimulated events such as DNA synthesis and induction of specific mRNA species. The results of these experiments indicated that, whereas methylamine treatment had no effect on EGF binding or internalization, vesicular translocation from endocytic vesicles to lysosomes was halted and processing of EGF was severely inhibited. The stimulation of DNA synthesis beginning 12 h after EGF exposure was also markedly inhibited by methylamine treatment. However, addition of methylamine alone produced a non-specific inhibition of DNA synthesis. The ability of EGF to induce specific transcription of the rat transin gene within 6 h of treatment was also not inhibited by methylamine treatment, but was actually increased in the presence of methylamine. These results suggest that at least some early transcriptionally regulated events induced by EGF do not require vesicular processing of EGF (or its receptor) and that the signal transduced by the binding of EGF to its receptor occurs in, or proximal to, the endocytic vesicles.

Animals