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At least 721 records · Page 40Linked to original sources
PubMed1995

Acetaminophen does not decrease hepatic 3'-phosphoadenosine 5'-phosphosulfate in mice.

Capacity-limited sulfation of chemicals is thought to be due to the limited availability of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the cosubstrate for sulfation, which in turn is limited by the availability of its precursor, inorganic sulfate. Because this concept evolved from experimental data obtained from rats, and species differences have also been reported on acetaminophen (AA) sulfation, this study examined the effects of AA on PAPS and sulfate concentrations in mice, another widely used experimental animal. AA lowered serum and liver sulfate concentrations approximately 50% in mice. However, contrary to observations in rats, AA (0-600 mg/kg i.p.) did not decrease hepatic PAPS concentrations in mice. In summary, these studies demonstrate that AA decreases serum and liver sulfate concentrations, but does not decrease hepatic PAPS concentrations in mice. These data indicate that 1) hepatic sulfation of high dosages of AA in mice is not limited by the availability of PAPS, and 2) there are significant species differences in the regulation of AA sulfation between rats and mice.

Acetaminophen↗
PubMed2004

Alternative oxygen-dependent and oxygen-independent ribonucleotide reductases in Streptomyces: cross-regulation and physiological role in response to oxygen limitation.

Ribonucleotide reductases (RNRs) catalyse the conversion of ribonucleotides to deoxyribonucleotides and are essential for de novo DNA synthesis and repair. Streptomyces spp. contain genes coding for two RNRs. We show here that the Streptomyces coelicolor M145 nrdAB genes encoding an oxygen-dependent class I RNR are co-transcribed with nrdS, which encodes an AraC-like regulatory protein. Likewise, the class II oxygen-independent RNR nrdJ gene forms an operon with a likely regulatory gene, nrdR, which encodes a protein possessing an ATP-cone domain like those present in the allosteric activity site of many class Ia RNRs. Deletions in nrdB and nrdJ had no discernible effect on growth individually, but abolition of both RNR systems, using hydroxyurea to inactivate the class Ia RNR (NrdAB) in the nrdJ deletion mutant, was lethal, establishing that S. coelicolor possesses just two functional RNR systems. The class II RNR (NrdJ) may function to provide a pool of deoxyribonucleotide precursors for DNA repair during oxygen limitation and/or for immediate growth after restoration of oxygen, as the nrdJ mutant was slower in growth recovery than the nrdB mutant or the parent strain. The class Ia and class II RNR genes show complex regulation. The nrdRJ genes were transcribed some five- to sixfold higher than the nrdABS genes in vegetative growth, but when nrdJ was deleted, nrdABS transcription was upregulated by 13-fold. In a reciprocal experiment, deletion of nrdB had little effect on nrdRJ transcription. Deletion of nrdR caused a dramatic increase in transcription of nrdJ and to a less extent nrdABS, whereas disruption of cobN, a gene required for synthesis of coenzyme B12 a cofactor for the class II RNR, caused similar upregulation of transcription of nrdRJ and nrdABS. In contrast, deletion of nrdS had no detectable effect on transcription of either set of RNR genes. These results establish the existence of control mechanisms that sense and regulate overall RNR gene expression.

Amino Acid Sequence↗
PubMed1992

Human retinal pigment epithelial cells cultured in hyperglycemic media accumulate increased amounts of glycosaminoglycan precursors.

Confluent human retinal pigmented epithelial cells were cultured on microcarrier beads in the presence of 5.6 or 26 mmol/l glucose with or without the aldose-reductase inhibitor Sorbinil (200 microM) for 2 wk. At the end of the incubation period, perchloric acid extracts were prepared and analyzed by 31P nuclear magnetic resonance spectroscopy. As assessed by this method, the phosphorylated metabolites of cells incubated with 5.6 or 26 mmol/l glucose differed significantly in the concentrations of a number of uridine diphosphate (UDP)-conjugated monosaccharides, which were elevated two- to threefold in cells incubated in 26 mmol/l glucose over control samples. The affected metabolites were identified (through a series of spiking experiments) to be UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine, and UDP-glucuronic acid. Coincubation of the cells with Sorbinil 200 microM in the presence of 26 mmol/l glucose had no effect on this accumulation. Under normal circumstances, these molecules selectively and sequentially are incorporated into the polysaccharide chains of glycosaminoglycans (GAGs), whose presence and distribution in the basement membranes is affected adversely by diabetes mellitus. These data suggest that the availability of the monosaccharide precursor is not the rate-limiting step for GAG synthesis in the presence of pathologic glucose concentrations. Thus, the lost GAG content in the basement membranes of diabetic patients may be caused by changes elsewhere in the biosynthesis and/or catabolism of the polysaccharide-linked protein molecules.

Aldehyde Reductase↗
PubMed1980

Flow sorting of antigen-binding B cell subsets.

Antigen binding was used as a probe in the definition of functional B cell heterogeneity. Unprimed, anti-Thy 1 and complement-treated spleen cells were stained with fluorescent trinitrophenylated bovine serum albumin (FL-TNP-BSA). These cells were sorted, fluorescence negative from fluorescence positive, by using a multiparameter cell sorter and assayed for precursor frequency in antibody responses to TNP by limiting dilution analysis. The cells that bound FL-TNP-BSA were demonstrated to be enriched for antibody-forming precursors to the antigens TNP-lipopolysaccharide (LPS), TNP-sheep red blood cells (SRBC), and TNP- or DNP-Ficoll, whereas the fluorescence negative cells were depleted for these responses. B cells that bound FL-TNP-BSA were then sorted into populations that bound a moderate or high amount of FL-TNP-BSA. The B cells responsive to TNP-LPS and TNP-SRBC were present in both the moderate and high binding populations. In contrast, the B cells responsive to TNP- or DNP-Ficoll were present only in the cells that bound a moderate amount of FL-TNP-BSA. These experiments suggest that there is a population of B cells in adult mouse spleen that binds large amounts of antigen, and that can respond to antigen carried on LPS or SRBC but not carried on Ficoll.

Animals↗
PubMed1994

Oligodendrocyte precursor quantitation and localization in perinatal brain using a retrospective bioassay.

Several late stages of the oligodendrocyte (OL) developmental lineage can be identified immunologically in the newborn rat brain. However, OL lineage-specific markers are not available for the detection of the less mature, yet determined, OL precursors. We have developed a retrospective bioassay, combining limiting dilution analysis with a novel culture system, that quantitatively assesses the developmental potential in vivo of phenotypically undefined OL precursors in order to (1) demonstrate their existence, (2) estimate their total number in the premyelinated rat brain, and (3) demonstrate their presence in regions distal to germinal zones at times previously predicted to be devoid of such cells. Between embryonic day (E) 21 and postnatal day (P) 0, cells determined to become oligodendrocytes increase in frequency approximately 5-fold in the whole brain (from one precursor for every 365 cells to 1 in 74), and approximately 2.5-fold in the telencephalon (from 1 in 298 to 1 in 115). From these data it is calculated that a pool of approximately 10(6) phenotypically undefined cells are present in the newborn brain that are able to differentiate into OL in vitro. Further, by applying this assay to tissue samples of subdomains of the developing cerebellum, we have demonstrated that such cells are present in large numbers as early as E20 in regions sparsely populated with cells expressing the blastic neural cell marker ganglioside GD3, suggesting that they migrated to this position as a pre-GD3-expressing cell. These results significantly change the predicted ontogeny of the oligodendrocyte lineage and should fuel the ongoing search for these early OL precursors.

Animals↗
PubMed2004

No predictive value of cytotoxic or helper T-cell precursor frequencies for outcome when analyzed from the graft after stem cell transplantation.

The predictive value of limiting dilution analyses (LDA) measuring cytotoxic and helper T-lymphocyte precursor (CTLp and HTLp) frequencies for outcome after stem cell transplantation (SCT) is still a matter of debate. One reason may be that CTLp and HTLp frequencies are determined in peripheral blood mononuclear cells (PBMC) and this responder cell population does not reflect the cell type composition of the graft. We assessed whether CTLp and HTLp LDA can predict complications after human leukocyte antigen (HLA)-identical SCT when CTLp and HTLp frequencies are analyzed in PBMC of the respective stem cell graft [bone marrow (BMMC) or granulocyte colony-stimulating factor (G-CSF)-mobilized PBMC] and compared to PBMC of PB. Host-specific CTLp frequencies measured in 25 patients and HTLp frequencies analyzed in 6 patients were low in all responder cell sources. CTLp and HTLp frequencies seen against HLA-mismatched unrelated third-party cells were high, but third-party-specific CTLp and HTLp frequencies were lower in G-CSF-PBMC than in PBMC ( p=0.047 for CTLp frequencies). Host-specific CTLp frequencies analyzed in all responder cell sources did not predict acute or chronic graft-versus-host disease (GVHD). Lower CTLp frequencies were detected in all responder cell sources from patients who relapsed after SCT than in patients without relapse, but the differences between both groups were statistically significant only in PBMC. In conclusion, a significant correlation was detected only between relapse and CTLp frequencies measured in PBMC. The lower frequency of third-party-specific cells in G-CSF-PBMC indicates that the mobilization procedure with G-CSF itself may influence results.

Acute Disease↗
PubMed2000

Expression of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors and sensitivity to TRAIL-induced apoptosis in primary B-cell acute lymphoblastic leukaemia cells.

Because tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2 ligand) preferentially kills malignant cells while sparing normal cells, it may be therapeutically useful against cancers, including those of haematopoietic origin. Although the activity of TRAIL has been studied in tumour cell lines and in a limited number of different primary tumours, its overall activity in a large number of uniform cases of primary tumours is not known. We therefore studied the activity of TRAIL in 29 primary precursor B-cell acute lymphoblastic leukaemia (ALL) samples. TRAIL was found to have a modest activity as it killed a maximum of 29% of ALL cells within 18 h compared with killing 75% of Jurkat cells. The sensitivity to TRAIL did not correlate with the pattern of TRAIL receptor expression or FLIP expression, as determined by Western blot analysis. The CD40 receptor, which can transduce survival signals in mature malignant B cells, was less frequently expressed on ALL cells, but incubation with an exogenous soluble CD40 ligand trimer did not rescue them from spontaneous apoptosis and did not mediate their resistance to TRAIL. Further, although ALL cells expressed TRAIL protein, they failed to kill target Jurkat cells in a TRAIL-dependent manner. Our data delineate major biological differences between mature and precursor malignant B cells and suggest a limited therapeutic role for TRAIL as a single agent in primary B-cell ALL.

Adolescent↗
PubMed1996

A limited temporal window for the derivation of multilineage repopulating hematopoietic progenitors during embryonal stem cell differentiation in vitro.

Embryonal stem cells have been shown to differentiate in vitro into all hematopoietic lineages. This has been used successfully as one approach to the study of genetic events occurring during haematopoiesis. However, studies on the commitment of mesodermal precursors to the hematopoietic lineage have been limited due to the inability to define a system in which embryonal stem (ES) cells will give rise to primitive hematopoietic stem cells in vitro. Using a colony forming assay (CFU-A), we determined that the earliest time point at which primitive multilineage hematopoietic precursors can be detected during ES cell differentiation in vitro in the absence of exogenous conditioned medium or stromal cell culture is 4 days. Lethally irradiated adult recipient mice that received differentiated ES cells from this time point survived for more than 3 weeks; and in two out three experiments, peripheral blood from these animals contained ES-derived progeny. Fluorescence activated cell sorting (FACS) found ES-derived CD45+ hematopoietic cells in both lymphoid and myeloid compartments at 12 weeks posttransplantation, suggesting that the population of day 4 differentiated ES cells contains primitive hematopoietic precursors. A preliminary RT-PCR analysis of gene expression around this time point suggests that there are very few hematopoietic cells present. This approach should prove useful in studies of genetic control of commitment to and maintenance of hematopoietic lineages in vitro and in vivo.

Amino Acid Sequence↗
PubMed1981

Regulation of clones responding to dextran B1355S. II. Response of T-dependent and T-independent precursors.

The existence of precursors for TI and TD alpha 1 leads to 3 dextran antigens in BALB/c mice was demonstrated. A T-dependent dextran antigen was prepared by coupling dextran B1355S to hemocyanin and subsequent digestion with dextranase. The PFC response of BALB/c mice primed with hemocyanin to dextran-hemocyanin was found to be 8 times higher than in unprimed animals. The splenic focus assay was adapted for the analysis of precursors responding to T-dependent and T-independent dextran antigens. Pretreatment of recipients with anti-thymocyte serum abolished the response in fragment cultures to dextran-hemocyanin but did not affect the response to dextran B1355S. The frequencies of precursors in the adult BALB/c mouse responding to dextran and dextran-hemocyanin were determined by limiting dilution analysis. The frequency of T-dependent precursors was found to be almost 3 times greater than the frequency of T-independent precursors.

Animals↗
PubMed1984

Rescue of the tumor-specific immune response of aged mice in vitro.

In contrast to young mice, old mice fail to reject a transplanted challenge of the highly immunogenic, ultraviolet light-induced tumor 1591-RE. Old mice also fail to mount a cytolytic tumor-specific immune response in vivo, and spleen cells of old mice are defective in their ability to generate tumor-specific T cells in vitro. In the present study we report the results of cell culture mixing experiments that show that this deficiency is due to a decreased responsiveness of the Lyt-2+ tumor-specific cytolytic T cell precursors of the old animals. We also demonstrate with limiting dilution analysis that the defective responsiveness is not due to a clonal exhaustion of the precursors. In fact, the responsiveness could be restored in vitro by culturing the spleen cells of old animals at high density or by the addition of excess Lyt-1-/Lyt-2-/2000-rad-resistant spleen cells from young or old mice. Our results suggest that the rescue of tumor immunity in old individuals may be possible, perhaps by educating effector cells in vitro for adoptive immunotherapy.

Aging↗
PubMed1978

The switch from IgM to IgG secretion in single mitogen-stimulated B-cell clones.

The frequency of mitogen-reactive B cells yielding an IgG plaque-forming cell (PFC) response has been determined in vitro by limiting dilution analysis under culture conditions which allow every growth-induced B cell to grow and mature into a clone of Ig-secreting cells. The frequencies of lipopolysaccharide (LPS)-and lipoprotein-reactive precursors for IgG-secreting cells in the spleen of 6--8 wk old C3H/Tif and of C57BL/67 mice were found to be between 1 in 30 and 1 in 40 B cells and, therefore, only one tenth of the frequencies of mitogen-reactive precursors of clones secreting IgM. All IgG-secreting cells developed by switching in clones which previously contained IgM-secreting cells. This was shown in two experiments where the total number of mitogen-reactive precursor yielding IgM-secreting cell clones was limited such that 82 or 90% of all responding cultures originated from one precursor. Thus, of 480 cultures in the first and 720 cultures in the second experiment, 86 and 98 cultures were found positive, yielding IgM-secreting cells at day 5. When the same cultures were assayed at day 7 for IgG-secreting cells 9 and 10 cultures were found positive. All 19 cultures with IgG-secreting cells previously had contained IgM-secreting cells. The probability that IgG-secreting cells and IgM-secreting cells would have arisen from independent precursors can be calculated using Fisher's exact test of independence. For the two experiments those probabilities are 3.4 X 10(-7) and 4.0 X 10(-9). Since we have previously shown that each cell in a mitogen-stimulated, growing B-cell clone divides, and that each dividing cell secretes Ig, we conclude from these experiments that the large majority--in our experiments all--of the IgG-secreting cells in mitogen-stimulated B-cell clones develop by switch from IgM-secreting cells. IgG-secreting cells develop either early or late during growth of a single IgM-secreting cell clone. The switch to IgG secretion, therefore, is not fixed in the time of clonal growth after mitogenic stimulation.

Animals↗
PubMed1992

The effect of age on mitogen responsive T cell precursors in human beings is completely restored by interleukin-2.

It is well known that the function of T lymphocytes is significantly impaired by advancing age. In the present study, attempts have been made to further characterize the T cell impairment of elderly subjects. Thus, we have performed limiting dilution microculture analysis to evaluate the precursor frequency of T lymphocytes responding to a mitogenic stimulus in old and young subjects. Furthermore we have evaluated the activity of recombinant interleukin-2 (rIL-2) on these cells. The results demonstrate that in older subjects the frequency of these precursors is significantly decreased. The in vitro treatment with rIL-2 increased the frequency of mitogen responsive T lymphocyte precursors in both groups so that the difference between the two groups was not significant. Thus present results extend the findings demonstrating that older subjects display an impairment of T cell functions and that IL-2 treatment may correct these alterations. In particular, they confirm the hypothesis that age-associated functional changes are more likely due to diminished numbers of reactive cells, than to a decline in the activity of all cells.

Adult↗
PubMed1987

Selective reduction of donor-specific cytotoxic T lymphocyte precursors in patients with a well-functioning kidney allograft.

We have recently developed a sensitive limiting dilution (LD) culture system to measure human alloreactive cytotoxic T lymphocyte precursors (CTL-p) in a given lymphoid cell population. We have now used this system to determine frequencies of donor HLA antigen-inducible CTL-p in the peripheral blood of human allograft recipients at various stages after transplantation. All patients (1 pancreas recipient and 9 kidney recipients) were on continuous cyclosporine treatment throughout the study. We report that, in patients with a well-functioning kidney graft (6/9), the number of donor-reactive CTL-p among peripheral blood lymphocytes decreased within 3-8 months after transplantation--in some cases (2/6) more than 10-fold. In contrast, frequencies of CTL-p with specificity for third-part HLA antigens remained largely unaltered in these patients. Furthermore, no decrease of donor-reactive CTL-p frequencies was seen in 3 of 4 patients showing clinical symptoms of graft rejection. These results indicate that functional clonal deletion of antigraft-reactive CTL-p may contribute to the state of graft tolerance in certain patients with a well-functioning kidney allograft.

Cells, Cultured↗
PubMed1993

Selective in vitro expansion of HLA class I-restricted HIV-1 Gag-specific CD8+ T cells: cytotoxic T-lymphocyte epitopes and precursor frequencies.

OBJECTIVE: To identify HIV-1 Gag cytotoxic T-lymphocyte (CTL) epitopes and HLA restriction of their recognition, and to define precursor frequencies of HIV-1 Gag-specific CTL in the blood of seropositive individuals. METHODS: B-lymphoblastoid cell lines (B-LCL) infected with recombinant vaccinia viruses (rVV) containing a gene coding for HIV-1 Gag (rVV-Gag) were fixed with paraformaldehyde (PFA) and used as antigen-presenting cells (APC) to stimulate peripheral blood mononuclear cells (PBMC) from asymptomatic HIV-seropositive individuals. Specific CTL activity was determined in 51Cr-release assays using B-LCL as targets after infection with rVV-Gag or after pulsing with partially overlapping peptides spanning the Gag sequence. RESULTS: In vitro stimulation resulted in an increased number of CD8+ T cells and CD45R0+ and HLA-DR+ cells. Gag-specific cytotoxicity, mediated predominantly by HLA class I-restricted CD8+ CTL, was observed in all seven individuals studied. Multiple HLA-restricted CTL epitopes were identified with a single culture from one of the individuals. Gag-expressing APC were successfully used as stimulator cells in limiting dilution analysis to determine CTL precursor (CTLp) frequencies. CONCLUSION: PFA-fixed rVV-Gag-infected autologous B-LCL can be used as stimulator cells in bulk PBMC cultures to identify CTL epitopes and to determine CTLp frequencies. This method will facilitate the analysis of HIV-1-specific CTL responses in HIV-infected and vaccinated individuals.

Antigen-Presenting Cells↗
PubMed1988

Role of T cells in regulating expression of the B cell repertoire. Anti-ssDNA precursor frequency of DBA/2 B cells is increased in the presence of T cells from NZB mice.

Splenic B cells from DBA/2 and NZB mice were compared with regard to precursor frequency of anti-ssDNA-producing cells. Using a modification of the splenic fragment assay, we show that NZB T cells are capable of increasing the frequency of expression of anti-ssDNA precursors in DBA/2 splenic B cells. When limiting numbers of splenic B cells of DBA/2 origin were adoptively transferred into an irradiated (1200 rad) recipient, the co-transfer of NZB T cells markedly increased the frequency of anti-ssDNA precursors in cultured splenic fragments. The anti-ssDNA produced under these conditions was exclusively IgM and exhibited a high degree of cross-reactivity with TNP and fluorescein. Thus, the increase in anti-ssDNA precursor frequency reflected an expansion of the B cell repertoire to include precursors of polyspecific antibody-producing cells that under normal circumstances are not expressed. The ability of NZB T cells to increase the anti-ssDNA precursor frequency was further defined by the CBA/N immunodeficiency gene xid, in that B cells from DBA/2.xid donors did not exhibit increased anti-ssDNA precursor frequency in the presence of NZB T cells. When NZB splenic B cells were co-transferred with DBA/2 T cells, the anti-DNA precursor frequency of the NZB B cells was not reduced. This study demonstrates that T cells can influence the emergency of B cell clones in an Ag-nonspecific manner. The well documented in vivo spontaneous polyclonal activation of NZB B cells may be secondary to T cell-mediated expansion of the B cell repertoire.

Animals↗
PubMed1993

High frequencies of cytotoxic T cell precursors against minor histocompatibility antigens after HLA-identical BMT: absence of correlation with GVHD.

Limiting dilution analysis was used to quantify the frequency of cytotoxic T cell precursors (CTLp) against minor histocompatibility (H) antigens induced by HLA-identical BMT. The development of CTLp was monitored serially in ten patients developing either acute (n = 3), acute and chronic (n = 4) or no (n = 3) GVHD. In blood samples of patients taken shortly after BMT (< 100 days) a high frequency of anti-recipient CTLp was found (mean 1/3433). With time, this value decreased to become undetectable (< 1/500,000) beyond 400 days. This occurred also in patients still suffering from chronic GVHD. In contrast, autologous BMT did not induce any measurable recipient-reactive CTLp at any time point after BMT. In the early phase of reconstitution after BMT the frequency of CTLp against allo HLA-antigens was measured in the same patients. The absence of a consistent increase of allo-specific CTLp indicates that the kinetics of CTLp against host minor H antigens does not merely reflect an overall changed cytolytic potential shortly after BMT. These results indicate that: (1) HLA-identical BMT induces high frequencies of minor H antigen-specific CTLps detectable in the blood during the early phase of reconstitution, and (2) the frequency of recipient-reactive CTL measured in the peripheral blood is not an adequate parameter for GVHD. These data therefore challenge the clinical value of in vitro measurement of recipient-reactive CTLs in the peripheral blood after HLA-identical sibling BMT.

Acute Disease↗
PubMed1995

Assessment of a functional role of auto-anti-idiotypes in idiotype dominance.

We have used a well-defined idiotypic system, the cross-reactive idiotype of A strain (CRIA) (Ab1) idiotype generated in A/J mice injected with arsonate coupled to keyhole limpet hemocyanin (ARS-KLH), to determine the frequency of precursors for auto-anti-idiotypic antibodies (auto-Ab2) in naive and immunized A/J mice by limiting dilution analysis after polyclonal activation by lipopolysaccharide. In naive animals, the precursor frequencies of auto-Ab2 B cells were below the limit of sensitivity of the technique in the majority of A/J mice, and could be detected in only 20% of the animals. Upon immunization with ARS-KLH, a large increase in auto-Ab2 precursor frequency was observed. This shift in frequency was not found when A/J mice were injected with KLH alone, or when BALB/c mice, which do not express the CRIA idiotype, were injected with ARS-KLH. To study the functional role of the auto-Ab2 B cells, we injected neonatal A/J mice with polyclonal rabbit Ab3 antibodies directed against a recurrent idiotype of auto-Ab2. Thereafter, these mice were injected with ARS-KLH. Although the anti-arsonate response level was normal, the CRIA Ab1 expression was reduced tenfold. Thus, the suppression of auto-Ab2 affects Ab1 dominance. We further show that the presence of maternal Ab1 can strongly modify the immune response of the offspring by inducing higher levels of the idiotype after immunization. Furthermore, IgM anti-arsonate antibodies were detected before immunization with antigen. From these data, we conclude that the affinity of antigen alone cannot explain the dominance of CRIA. Network selection is important in the shaping of the available repertoire.

Adjuvants, Immunologic↗
PubMed1980

[Activation of the anticoagulant system by prethrombin 2, a thrombin precursor].

Prethrombin 2, and immediate precursor of thrombin, was obtained by limited trypsin or active factor X proteolysis by prethrombin 1. The conversion of prethrombin 1 to prethrombin 2 does not occur in the absence of enzymes. It has been shown that factor V has no influence on the rate of thrombin generation from prethrombin 2 and that prethrombin itself has no coagulant or esterase activity. Intravenous injection of prethrombin 2 preparations led to an increase in plasma recalcification time, overall fibrinolytic activity and non-enzymatic fibrinolysis. In addition, there was observed a considerable increase in fibrinogen-heparin complex activity. The data obtained indicate excitation of the anticoagulant system with intravenous injection of small doses of prethrombin 2.

Animals↗