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At least 433 records · Page 24Linked to original sources

PubMed1988

Effect of prenatal exposure to ethanol on the development of cerebral cortex: I. Neuronal generation.

Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation. A proliferation index, which was based on the amount of autoradiographic signal over each labeled neuron, indicated that an additional, late surge in proliferative activity occurred in Et-treated rats on GD 20-21. The amount of [3H]thymidine incorporated each day was determined by biochemical analyses. In Ct-treated rats, incorporation increased to a maximum on GD 17 and decreased thereafter. In Et-treated rats, there were two maxima, the first on GD 18 and the second on GD 20. These data fully support the findings of the autoradiographic analyses. The present data show that neuronal generation is profoundly affected by ethanol. Such disturbances result from ethanol-induced abnormalities in neuronal proliferation and migration.

Animals↗

PubMed2004

Role of protease-activated and ADP receptor subtypes in thrombin generation on human platelets.

The activated platelet surface serves as an integral part of the prothrombinase complex upon activation by potent platelet agonists such as thrombin and collagen. We determined the receptor specificity through which thrombin was enhancing collagen-induced thrombin generation. Whereas SFLLRN or AYPGKF alone produced minimal thrombin generation or phosphatidylserine exposure through protease activated receptor (PAR) stimulation, they caused a leftward shift in the collagen-induced thrombin generation dose-response curve. Although SFLLRN or AYPGKF potentiated collagen-induced thrombin generation, neither of them potentiated to the same extent as thrombin. However, SFLLRN and AYPGKF together potentiated collagen-induced thrombin generation to the same extent as thrombin. We conclude that thrombin mediates its procoagulant activity through activation of both PAR1 and PAR4 receptors. Similarly, neither PAR1 nor PAR4 stimulation alone mimicked the annexin V-binding response caused by thrombin stimulation. The combination of PAR activating peptides caused minimal increases in annexin V binding, but caused significant thrombin generation, suggesting that events other than phosphatidylserine exposure may play a role in platelet prothrombinase complex formation. We also investigated the ability of ADP to potentiate agonist-induced thrombin generation. Whereas P2Y(1) antagonism did not affect collagen or thrombin-induced thrombin generation, P2Y(12) antagonism did decrease both collagen- and thrombin-induced thrombin generation, suggesting that ADP potentiates thrombin generation primarily through the P2Y(12) receptor. Collectively, these results suggest that stimulation of both the PAR1 and PAR4 receptors are necessary for thrombin-induced procoagulant activity, and that the P2Y(12) receptor, but not the P2Y(1) receptor, is responsible for the potentiation of agonist-induced platelet procoagulant activity.

Annexin A5↗

PubMed2006

Generation of platelet angiostatin mediated by urokinase plasminogen activator: effects on angiogenesis.

BACKGROUND: Angiogenesis, the growth of new capillaries from pre-existing blood vessels, is regulated by a balance between its promoters and inhibitors. Platelets are an important circulating store of angiogenesis regulators. We have previously identified the angiogenesis inhibitor angiostatin in human platelets. AIM: To identify the mechanism of platelet angiostatin generation and its pharmacological regulation. METHODS: Platelet aggregometry, flow cytometry, Western blot, zymography, immunofluorescence microscopy, matrigel-induced angiogenesis of human umbilical vein endothelial cells (HUVECs), and a panel of selective proteinase inhibitors were used to study the mechanism of angiostatin generation by platelets, its pharmacological regulation, and effects on angiogenesis. Release of pro-MMP-2 by HUVECs was also used to quantify angiogenesis. RESULTS: Platelet membranes were identified as the site of angiostatin generation from plasminogen. Generation of angiostatin by platelet membranes was not affected by a matrix metalloproteinase (MMP) inhibitor, phenanthroline, but was inhibited by serine proteinase inhibitors aprotinin, leupeptin, plasminogen activator inhibitor-1, and selective inhibitor of urokinase plasminogen activator (uPA), uPA-STOP(TM). Angiostatin generation by intact platelets was inhibited by aprotinin, and the resulting incubate promoted angiogenesis to a greater extent than incubate where angiostatin generation occurred. Furthermore, HUVECs incubated with reaction mixture, where angiostatin generation was inhibited, released more pro-MMP-2 than HUVECs incubated with supernatants, where angiostatin generation occurred. CONCLUSIONS: We conclude that; (i) platelets constitutively generate angiostatin on their membranes; (ii) this mechanism is dependent on uPA, but not, MMPs; and (iii) inhibition of platelet angiostatin generation can further promote angiogenesis.

Angiostatins↗

PubMed2006

The influence of age on in vitro plasmin generation in the presence of fibrin monomer.

BACKGROUND AND OBJECTIVES: The components of the fibrinolytic system interact to generate plasmin from its zymogen form, plasminogen. At birth, all the components of the fibrinolytic system are present but with differing plasma concentrations. The present study was undertaken to explore the effect of physiological, age-dependent factors of the fibrinolytic system during childhood on the capacity to generate plasmin. DESIGN AND METHODS: Total plasmin generation was measured in venous plasma from umbilical cords and adults, on plastic and cell surfaces, in the presence of fibrin monomer, Desafib. Plasminogen, its inhibitors alpha2-antiplasmin and plasminogen activator inhibitor type 1, and plasmin-alpha2-antiplasmin complex in the time samples were assayed by enzyme-linked immunosorbent assay. The effect of addition of plasminogen on the plasmin generation in cord plasma and the effect of lipoprotein on adult and cord plasmin generation were measured. RESULTS: On the surface of human umbilical vein endothelial cells, onset of plasmin generation was earlier (40 min) compared to plastic (60 min) but total plasmin generation was similar on both surfaces. The addition of plasminogen to cord plasma increased plasmin generation. Supplementation of lipoprotein in adult plasma had an inhibitory effect, but there was no significant effect in cord plasma. INTERPRETATIONS AND CONCLUSIONS: Plasmin generation is reduced in newborn compared to adult plasma. Decreased plasmin generation in cord plasma is likely due to decreased plasminogen concentration. The antifibrinolytic effect of lipoprotein is more pronounced in adults as compared to newborns due to the presence of higher plasminogen concentration.

Adult↗

PubMed1996

Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis".

The murine/human chimeric monoclonal antibody fragment (c7E3 Fab) blocks GPIIb/IIIa and alpha v beta 3 receptors, inhibits platelet aggregation, and decreases the frequency of ischemic events after coronary artery angioplasty in patients at high risk of suffering such events. Although inhibition of platelet aggregation is likely to be the major mechanism of c7E3 Fab's effects, since activated platelets facilitate thrombin generation, it is possible that c7E3 Fab also decreases thrombin generation. To test this hypothesis, the effects of c7E3 Fab and other antiplatelet agents were tested in a thrombin generation assay triggered by tissue factor. c7E3 Fab produced dose-dependent inhibition of thrombin generation, reaching a plateau of 45-50% inhibition at concentrations > or = 15 micrograms/ml. It also inhibited thrombin-antithrombin complex formation, prothrombin fragment F1-2 generation, platelet-derived growth factor and platelet factor 4 release, incorporation of thrombin into clots, and microparticle formation. Antibody 6D1, which blocks platelet GPIb binding of von Willebrand factor, had no effect on thrombin generation, whereas antibody 10E5, which blocks GPIIb/IIIa but not alpha v beta 3 receptors decreased thrombin generation by approximately 25%. Combining antibody LM609, which blocks alpha v beta 3 receptors, with 10E5 increased the inhibition of thrombin generation to approximately 32-41%. The platelets from three patients with Glanzmann thrombasthenia, who lacked GPIIb/IIIa receptors but had normal or increased alpha v beta 3 receptors, supported approximately 21% less thrombin generation than normal platelets. We conclude that thrombin generation initiated by tissue factor in the presence of platelets is significantly inhibited by c7E3 Fab, most likely in part through both GPIIb/IIIa and alpha v beta 3 blockade, and that this effect may contribute to its antithrombotic properties.

Acute Disease↗

PubMed2004

Response to vocational rehabilitation during treatment with first- or second-generation antipsychotics.

OBJECTIVE: Second-generation antipsychotics may enhance the rehabilitation of individuals with schizophrenia. The authors hypothesized that clients receiving second-generation antipsychotics would use vocational rehabilitation services more effectively and would have better employment outcomes than those receiving first-generation antipsychotics. METHODS: Ninety unemployed clients with schizophrenia and related disorders who were beginning a vocational rehabilitation program were followed for nine months. Three groups were defined according to the medication in use at study entry: olanzapine (N=39), risperidone (N=27), or first-generation antipsychotics only (N=24). Participants were interviewed monthly. RESULTS: The olanzapine and risperidone groups did not differ on any employment outcomes. On most vocational indicators, clients receiving second-generation agents did not differ from those receiving first-generation agents. However, at nine months the second-generation group had a significantly higher rate of participation in vocational training; a trend was found toward a higher rate of paid employment. All groups showed substantial improvement in employment outcomes after entering a vocational program. CONCLUSIONS: The hypothesis that second-generation antipsychotics promote better employment outcomes than first-generation antipsychotics was not upheld. However, second-generation agents appear to be associated with increased participation in vocational rehabilitation.

Adult↗

PubMed1986

Prostacyclin generation by cultured human vascular endothelial cells with reference to angiotensin I-converting enzyme.

Prostacyclin (PGI2) generation has been known to be regulated by several endogenous vasoactive substances, and in this study the relationship between angiotensin I-converting enzyme (ACE) related substances and PGI2 generation was investigated using cultured human vascular endothelial cells. Addition of angiotensin I (AI) or bradykinin (BK) enhanced PGI2 generation and increased the level of ACE activity in the culture medium, while the addition of ACE inhibitor (captopril) caused a dose dependent suppression of PGI2 generation and ACE activity. The enhancement of PGI2 generation induced by AI or BK was not affected by pretreatment with captopril, and angiotensin II (AII) did not show any effect on either PGI2 generation or ACE activity. Through these experimental results, the conversion of AI to AII by ACE was considered not to cause the enhancement of PGI2 generation. Captopril solely inhibited PGI2 generation and the reported hypothesis that captopril enhances PGI2 generation by the accumulation of AI or BK via inhibition of ACE was not confirmed in this experimental system. Rather, it is proposed that AI or BK induced PGI2 generation may be regulated by the increased breakdown of AI or BK, as an autoregulation mechanism, that is derived from increased ACE activity by AI or BK.

Angiotensin I↗

PubMed1995

Dietary intake among Mexican-American women: generational differences and a comparison with white non-Hispanic women.

OBJECTIVES: Although Mexican Americans consume diets that may protect them against adverse health, dietary advantages may disappear with increased acculturation. This study examined whether the nutrient intake of second-generation Mexican-American women of childbearing age deteriorates compared with that of first-generation Mexican-American women and approximates that of White non-Hispanic women. METHODS: Data on the absolute and relative intake of eight nutrients were obtained from a 24-hour recall and compared among 475 first-generation and 898 second-generation Mexican-American women, and among 2326 White non-Hispanic women. RESULTS: Although first-generation Mexican-American women were of lower socioeconomic status than were second-generation or White non-Hispanic women, they had a higher average intake of protein; vitamins A, C, and folic acid; and calcium than the other two groups. Whereas the mean adequacy ratio of the eight nutrients studied was highest in first-generation Mexican women, it was lowest in their second-generation counterparts. CONCLUSIONS: First-generation Mexican women stand a markedly lower risk of eating a poor diet than second-generation Mexican women, whose nutrient intake resembles that of White non-Hispanic women.

Acculturation↗

PubMed1994

Ten generations of selection for predicted weight of testes in swine: direct response and correlated response in body weight, backfat, age at puberty, and ovulation rate.

Selection for predicted weight of testes at 150 d of age (PWT) was practiced for 10 generations to determine the effect on reproductive and growth traits in swine. Mass selection among boars (line TS) or random selection (line C) was practiced beginning with the F3 generation of a Large White x Landrace composite population. Population size in each line was 40 to 45 litters by 15 sires per generation. Responses were estimated by regressions on cumulative selection differentials for PWT and on generation number and by mixed-model derivative-free REML procedures. The realized heritability of PWT was .35 +/- .02 and the response per generation was 19 g (P < .01). Correlated responses in body weight were .95 +/- .37 (140 d) and 1.13 +/- .42 kg (160 d) per generation for boars and .70 +/- .32 (130 d) and .64 +/- .46 kg (180 d) per generation for gilts. Response in backfat was .08 +/- .14 mm per generation in boars and .16 +/- .14 mm in gilts. Negative genetic trends occurred in age at puberty in both lines, but the difference between lines was not significant. At Generation 10, ovulation rate was .76 +/- .43 eggs more for gilts of the TS line than for C gilts. Genetic correlations of PWT with other traits are presented. Heritability of PWT was moderately high and its phenotypic variance was large; therefore, a high rate of response of 5.5% per generation occurred. Selection for PWT was not effective in decreasing age at puberty or increasing ovulation rate of daughters.

Adipose Tissue↗

PubMed2000

The effect of DDAVP infusion on thrombin generation in platelet-rich plasma of von Willebrand type 1 and in mild haemophilia A patients.

In von Willebrand disease (vWD) type 1 and mild haemophilia A patients we studied the effect of an infusion of DDAVP (0.3 microg/kg body weight) on thrombin generation in platelet-rich plasma (PRP) and platelet-poor plasma (PPP). Baseline thrombin generation in PRP was diminished both in the haemophilia A and vWD patients. It was normal in vWD plasma when sufficient procoagulant phospholipids were present, either via adding phospholipid vesicles to PPP or via scrambling of the platelet membrane with ionomycin in PRP. In haemophilia A plasma, thrombin generation did not normalize by providing procoagulant phospholipids. Treatment with DDAVP temporarily restored thrombin generation in PRP to normal in both diseases. To investigate the individual roles of von Willebrand factor (vWF) and factor VIII, we also studied the effect of factor VIII infusion on thrombin generation in a severe haemophilia patient. It appears that at a fixed normal vWF concentration, <25% factor VIII is sufficient for normal thrombin generation in PRP. At a sufficient factor VIII concentration, however, thrombin generation is still lower than normal in vWD patients; approximately 40% of vWF is required for half-normal thrombin generation in PRP. It thus appears that vWF is also a clotting factor, in the sense that it is required for normal thrombin generation. This underlines the importance of the interaction between coagulation and the platelets in normal haemostasis. Thrombin generation in PRP appears to be a suitable test to reflect the combined function.

Deamino Arginine Vasopressin↗

PubMed2001

[Effects of second and third generation oral contraceptives on hemostasis].

Use of oral contraceptives induce changes in haemostatic parameters: changes occur in the procoagulant, anticoagulant, and fibrinolytic systems. The increased risk of venous thromboembolism with use of third, as compared with second generation oral contraceptives, found in epidemiological studies, has stimulated new research in haemostatic changes induced by both generations of oral contraceptives. A randomized crossover study showed that use of the third generation pill caused a greater increase of factor VII and prothrombin and a more pronounced decrease of factor V than the second generation pill. Acquired resistance to activated protein C (APC) was induced more strongly by preparations of the third than by those of the second generation. The concentration of protein S decreased markedly exclusively during use of the third generation pill, while it did not change during use of the second generation pill. The oral contraception-related effects on the anticoagulant system strongly resemble those of some forms of hereditary thrombophilia. If a woman with hereditary APC resistance (caused by factor V Leiden) uses oral contraceptives as well, and especially when she uses those of the third generation, she is subject to a considerable increase of the risk of venous thrombosis and becomes even more resistant to the anticoagulant action of protein C. In view of the epidemiological backgrounds of the difference in risk of thrombosis between second and third generation contraceptives, the second generation pill is recommended as the first choice for oral contraception.

Activated Protein C Resistance↗

PubMed1998

Ethnic Identity in Second (Nisei), Third (Sansei), and Fourth (Yonsei) Generation JapaneseAmericans in Hawaii.

PURPOSE. The present investigation tested the linear hypothesis of generational assimilation/acculturation among second (Nisei), third (Sansei) and fourth (Yonsei) generations of JapaneseAmericans in Hawaii. METHODOLOGY. Investigators assessed ethnic identity using the Ethnic Identity Questionnaire (EIQ), a widely studied instrument especially designed for use with Japanese ancestral populations. PRINCIPAL FINDINGS. Results indicated that when holding gender constant, fourth-generation (Yonsei) JapaneseAmericans residing in Hawaii evidenced no differences from third-generation (Sansei) JapaneseAmericans in the extent of their ethnic identity with traditional Japanese culture as measured by the Ethnic Identity Questionnaire (EIQ). This finding can be contrasted to previous results comparing first (Issei), second (Nisei), and third (Sansei) generations of Japanese-Americans in which the different generations demonstrated a linear progression toward reduced identification with Japanese culture. When gender by generation relationships were analyzed using a two (male versus female) by three (Nisei, Sansei, Yonsei) cell analysis of variance, gendergeneration inter-relationships were found, suggesting ethnic identity is complexly determined by gender variables. CONCLUSIONS. Ethnic identity appears to be a function of local, national, and even international factors. Simple linear assimilation hypotheses do not capture the complexity of the ethnic identification process. This is the first evidence of an attenuation in the progressive reduction of ethnic identification with Japanese culture among Japanese-Americans living in Hawaii across the generations. Efforts must be made to study acculturation within specific behavioral domains and contexts, and to control for generation, age and historical variables. RELEVANCE TO ASIAN-AMERICAN/PACIFIC ISLANDER POPULATIONS. This article adds to our understanding of assimilation/acculturation processes among JapaneseAmericans and raises questions about this process for other recent Asian immigrant groups. KEY WORDS. Ethnic Identity, Japanese-Amercans, Acculturation, Assimilation.

Journal Article↗

PubMed2000

[A comparative study on nutrient accumulation and distribution of different generations of Chinese fir plantations].

The nutrient accumulations and distribution of different generation of Chinese fir plantations in central production areas of China were studied through the investigation of plantation with different generation(first, second and third), ages (5, 10, 15, 20 years old) and sites(site index 14, 16 and 18). The nutrient accumulations and distribution of Chinese fir plantations were greatly influenced by the number of planting generation. Nutrient accumulation and utilization efficiency in tree layer of Chinese fir plantations declined with the increasing planting generation number, with the first generation > the second > the third; while the nutrient accumulation of understory vegetation was increased with the increasing of planting generation number. Compared with the first generation plantations, nutrient accumulation of tree layer of the second and the third generations decreased by 17.56% and 36.24% respectively, and the third generation platation decreased by 22.65% than the second generation. Meanwhile, successive planting resulted in a decreasing nutrient utilization efficiency of Chinese fir plantation, and an increasing nutrient necessary for dry matter production per unit, which is disadvantageous to the maintaining of soil fertility, but beneficial to the nutrient accumulation of understory vegetation.

Abies↗

PubMed2005

Cross-generational effect of prenatal morphine exposure on neurobehavioral development of rat pups.

Prenatal exposure to opiates can have devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. The present study was aimed at identifying cross-generational effects of prenatal morphine exposure in Sprague-Dawley rats. Pregnant rats were injected subcutaneously with either saline or morphine (10 mg/kg) twice daily during gestational days 11-18. Litter size, percentage of males and females, anogenital distances (AGDs), righting reflex, and body weight were assessed in prenatally morphine-exposed pups (first generation) and their offspring (second generation). Both prenatally morphine-exposed pups and offspring of prenatally morphine-exposed dams exhibited an increased latency to right. Additionally, second generation pups were slower in righting than first generation pups. During the early postnatal period the second generation pups weighed less than the first generation regardless of drug exposure. The AGDs of second generation male pups were decreased relative to the first generation. Our data provide important novel information about the trans-generational effects of maternal opiate abuse that may be useful for understanding/evaluating the teratogenic effects of prenatal opiate exposure.

Analgesics, Opioid↗

PubMed2005

Shear bond strength of one 4th and two 7th generation bonding agents when used by operators with different bonding experience.

PURPOSE: To test the hypothesis that simpler-to-use dentin adhesives (7th-generation adhesives) perform better when used by inexperienced operators than do the more complex 4th-generation adhesives. MATERIALS AND METHODS: Six operators with no previous experience regarding dental adhesives, three residents in pediatric dentistry, and three experienced dentists used one 4th-generation dentin adhesive (MA) and two 7th-generation adhesives (MB and MC). With each adhesive, each operator performed 6 bondings to enamel and 6 bondings to dentin. After 24 h of storage in water at 37 degrees C, the shear bond strength was determined. RESULTS: The pooled results showed that the bond strength to dentin was higher (p < 0.05) than that to enamel (dentin mean value = 14.0 MPa, SD = 9.1 MPa; enamel mean value = 11.9 MPa, SD = 7.1 MPa), and that adhesive MA performed better (p < 0.05) than adhesives MB and MC (inexperienced operators = 16.2 +/- 10.9 MPa; residents in pedodontics = 12.0 +/- 6.8 MPa, and experienced operators = 10.7 +/- 4.8 MPa). Of the two 7th-generation adhesives, one performed better on enamel than on dentin, while the other 7th-generation adhesive performed better on dentin than on enamel. Regarding operators, there were large individual variations. The inexperienced bonders performed as well as the residents (p > 0.05), while the experienced operators performed best (p < 0.05). CONCLUSION: In general, the tested 4th-generation adhesive performed better than the 7th-generation adhesives. Even inexperienced operators performed better with the more difficult-to-use 4th-generation adhesives than with the 7th-generation adhesives. Dentin adhesion was stronger than enamel adhesion.

Acid Etching, Dental↗

PubMed1992

Stimulus presentation using a programmable signal generator.

Event related potential experiments frequently require the presentation of complicated stimulus patterns to the subject. As the complexity and number of different types of stimuli presented to the subject increase there is a corresponding increase in the amount and complexity of the equipment required to generate the stimuli. Software was developed for complex stimulus presentation which uses a programmable arbitrary/function generator. The various stimulus patterns are stored in digital form in the memory of the signal generator and can be recalled by number. Prior to presentation of a particular stimulus pattern the number of that pattern is sent by the control program to the generator for recall from memory. The signal generator is set to operate in external trigger mode and at the proper time for stimulus presentation the generator is triggered by the control program. The use of the programmable signal generator allows replacement of the typical stimulus presentation equipment such as gates, signal generators, and attenuators by this the programmable generator and provides getter flexibility as to the type and complexity of stimuli which can be generated.

Electric Stimulation↗

PubMed1990

Thrombin generation in newborn plasma is critically dependent on the concentration of prothrombin.

The ability to generate thrombin is decreased and delayed in plasma from the healthy newborn infant compared to the adult. Only 30 to 50% of peak adult thrombin activity can be produced in neonatal plasma. To test whether this observation can be explained by the low neonatal levels of the contact or vitamin K dependent factors, we measured neonatal thrombin generation after raising the concentration of these factors to adult values. We also determined whether the addition of a variety of blood products to neonatal plasma improved thrombin generation. An amidolytic method was used to quantitate intrinsic (APTT) and extrinsic (PT) pathway thrombin generation in defibrinated pooled cord plasma from healthy term infants. Added individually, factors VII, IX, X or the contact factors (CF) failed to alter the rate or the total amount of thrombin generated in neonatal plasma. In contrast, the addition of prothrombin increased the total amount of thrombin generated to above adult values in both the APTT and the PT systems but did not alter the rate of thrombin generation. The rate of thrombin generation in cord plasma shortened after a combination of II, IX, X and CF was added to the APTT system or II, VII and X to the PT system. In both systems, the total amount of thrombin generated was linearly related to the initial prothrombin concentration. Each of fresh frozen plasma, cryoprecipitate, plasma from platelet concentrates, or factor IX concentrate (in amounts used therapeutically) caused an increase in the total amount of thrombin generated which was related to the increase in prothrombin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors↗

PubMed1984

Control of immune complex and zymosan-mediated anaphylatoxin generation by proteins B and H of the alternative complement pathway.

The generation of histamine releasing activity (HRA) from human basophils in fresh serum by tetanus toxoid (Te)/anti-Te complexes or by zymosan can be modulated through introduction of incremental amounts of proteins B and H of the alternative complement pathway. Serum treated at 50 degrees in order to abolish alternative pathway-mediated haemolytic activity, lost 90% of its capacity to generate HRA upon addition of Te/aTe; such loss could be reversed through additions of purified B. Amounts of B sufficient to restore normal alternative pathway haemolytic activity also restored HRA induced by Te/aTe; as little as a 33% increase above the normal serum concentration of B increased the capacity to support Te/aTe induced HRA by a factor of 1.4. In contrast, additions of incremental doses of purified H to fresh serum reduced generation of HRA by both Te/aTe and zymosan. Total inhibition was achieved by increasing the serum H concentration by 12.5-30%; further increases of H up to 200% again permitted HRA generation induced by immune complexed aTe. H also inhibited Te/aTe induced HRA in a serum heated at 50 degrees but only 30% inhibition of HRA could be achieved over a range of H inputs up to 187% above normal serum concentration. Additions of H also inhibited HRA generation in fresh serum when induced with plain or C3b-coated zymosan (Z) particles. By increasing the serum concentration of H from 12.5 to 125%, dose-dependent inhibition of HRA generation was observed; the H input necessary to suppress 48% of HRA generation was ten times higher when HRA was generated by Z-C3b than by plain zymosan. Thus, the complement-dependent generation of HRA from fresh serum strongly depends on modest variations in the concentrations of the two regulatory proteins B and H of the alternative complement pathway, suggesting their direct effect on generation of anaphylatoxins C3a and C5a.

Anaphylatoxins↗