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PubMed1997

[Effects of erythromycin on H2O2 generation by neutrophils].

Low-dose long-term erythromycin therapy has been reported to be effective in diffuse panbronchiolitis, but the mode of action remains obscure. We therefore evaluated the effect of erythromycin the generation of H2O2 by neutrophils. In vitro, erythromycin (0.1, 1.0, and 20 micrograms/ml) suppressed both spontaneous and PMA-stimulated H2O2 generation. H2O2 generation by neutrophils obtained from peripheral blood and from bronchoalveolar lavage fluid from patients with diffuse panbronchiolitis was higher than that from healthy controls. After erythromycin therapy, H2O2 generation by neutrophils was lower. Compared with the control, H2O2 generation by peripheral neutrophils was low in the patients who responded clinically to erythromycin therapy, but was high in those who did not respond. These results suggest that at least some of the therapeutic effect of erythromycin in patients with diffuse panbronchiolitis is due to reduction in H2O2 generation by neutrophils.

Anti-Bacterial Agents↗
PubMed1997

Thrombin generation by apoptotic vascular smooth muscle cells.

Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface, classically provided by activated platelets. We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after serum withdrawal. In this study, using a chromogenic assay, we have shown thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area under the thrombin-generation curve (AUC) of 305 +/- 17 nmol x min/L and a peak thrombin (PT) of 154 +/- 9 nmol/L. The thrombin-generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets (P = .003 for AUC; P = .0002 for PT) and similar to calcium-ionophore activated platelets (AUC of 332 +/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2). Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8 nmol x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P < .0001 for AUC and PT). VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal (P = .0002 for AUC and PT). VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/- 4 nmol/L). We conclude that apoptotic VSMCs possess a significant thrombin-generating capacity secondary to phosphatidylserine exposure. Apoptotic cells within atherosclerotic plaques may allow local thrombin activation, thereby contributing to disease progression.

Adenovirus E1A Proteins↗
PubMed1997

Cyclooxygenase-2-dependent delayed prostaglandin D2 generation is initiated by nerve growth factor in rat peritoneal mast cells: its augmentation by extracellular type II secretory phospholipase A2.

When rat serosal connective tissue mast cells (CTMC) were stimulated with nerve growth factor (NGF), the immediate prostaglandin D2 (PGD2) generation was followed by delayed PGD2 generation that occurred between 2 and 24 h, reaching levels as high as 50 ng and 260 ng/10(6) cells in the absence or presence of lysophosphatidylserine (lysoPS), respectively. This delayed PGD2 generation was accompanied by de novo induction of cyclooxygenase (COX)-2, with NGF and lysoPS acting as inducer and enhancer, respectively. COX-2 induction and the attendant delayed PGD2 generation in CTMC were modestly induced by c-kit ligand, but not by Fc epsilonRI cross-linking. This indicated that the stimulus specificity differed from that observed in the immediate phase, in which NGF, c-kit ligand, and Fc epsilonRI cross-linking, either in combination with each other or with lysoPS as a cofactor, elicited comparable levels of PGD2 generation within 10 min, reaching 10 to 20 ng/10(6) cells. Addition of type II secretory phospholipase A2 (sPLA2), a PLA2 isoform that is detected in microg/ml levels in inflammatory exudates, to NGF-stimulated CTMC significantly augmented delayed, but not immediate, PGD2 generation, and this augmentative effect was mediated in part by the enhancement of COX-2 expression by sPLA2. These results suggest that CTMC have the capacity to produce PGD2 over a prolonged period in the presence of tissue-derived cytokines and sPLA2 in a COX-2-dependent manner.

Animals↗
PubMedDate not supplied

[Carbon dioxide inhibits the generation of active forms of oxygen in human and animal cells and the significance of the phenomenon in biology and medicine].

Carbon dioxide (CO2) influence in generation of active oxygen forms (AOF) in human mononuclear cells (blood phagocytes and alveolar macrophages) and animal cells (tissue phagocytes, parenchymal and interstitial cells of liver, kidney, lung, brain and stomach) was investigated. The AOF generation was examined by the methods of chemiluminiscence (CL) using luminol, lucigenin and NBT (nitro blue tetrazolium) reaction. It was established that CO2 in concentrations similar to those in blood (5.1%, pCO2 37.5 mmHg) and at high concentrations (8.2%, pCO2 60 mmHg; 20%, pCO2 146 mmHg) showed pronounced inhibitory effect on the AOF generation in all the studied cells (usually reducing it 2 to 4 times). Those results were obtained not only after the direct contact of isolated cells with CO2, but also after the whole body exposure to CO2. Besides, it was established that venous blood gas mixture (CO2 - 45 mmHg, +O2 - 39 mmHg, + N2 - 646 mmHg) inhibited the AOF generation in cited cells more than the arterial blood gas mixture (CO2 - 40 mmHg, + O2 - 95 mmHg, + N2 - 595 mmHg). Carbon dioxide action mechanism was developed partially through the inhibition of the OAF generation in mitochondria and through deceleration of NADPH oxidative activity. Finally, it was established that CO2 led to the better coordination of oxidation and phosphorylation and increased the phosphorylation velocity in liver mitochondria. The results clearly confirmed the general property of CO2 to inhibit significantly the AOF generation in all the cell types. This favors the new explanation of the well-known evolutionary paradox: the Earth life and organisms preservation when the oxygen, that shows toxic effects on the cells through the AOF, occurs in the atmosphere. The results can also be used to explain in a new way the vasodilating effect of CO2 and the favorable hypercapnotherapy influence on the course of some bronchial asthma forms. The results are probably significant for the analysis of important bio-ecological problem, such as the increase of CO2 concentration in the atmosphere and its effect on the humans and animals.

Adult↗
PubMed1996

Effects of calyculin A and FK506 on the O2- generation of rat peritoneal macrophages.

To investigate the role of phosphatase in O2- generation, the effects of the potent phosphoprotein phosphatase inhibitors, Calyculin A and FK506, were analyzed during phagocytosis using rat peritoneal macrophages. O2- generation was continuously measured after addition of opsonized zymosan (op. ZY) or IgG-coated zymosan (IgG-ZY). The rate of O2- generation was directly proportional to the number of macrophages, up to 1-2 x 10(6) cells/ml. It was found that the rate and duration of O2- generation were markedly inhibited by Calyculin A. The addition of 100 nM of Calyculin A reduced O2- generation to about one-tenth of the control value. In contrast, FK506 did not inhibit O2- generation, suggesting that calcium calmodulin phosphatase is not involved in the activation of NADPH oxidase. This result indicates that the process of dephosphorylation might involve activation of NADPH oxidase as a control mechanism in phagocytosis by rat peritoneal macrophages. Furthermore, since Calyculin A is an inhibitor of phosphatase 1 and 2A, it is suggested that dephosphorylation may be evoked by these phosphatases.

Animals↗
PubMed1997

Bidirectional effect of interleukin-10 on early murine B-cell development: stimulation of flt3-ligand plus interleukin-7-dependent generation of CD19(-) ProB cells from uncommitted bone marrow progenitor cells and growth inhibition of CD19(+) ProB cells.

B-cell commitment and early development from multipotent hematopoietic progenitor cells has until recently been considered to be dependent on direct interaction with stromal cells. We recently showed that the flt3 ligand (FL) has a unique ability to interact with interleukin-7 (IL-7) to directly and selectively promote B-cell development from murine bone marrow progenitor cells with a combined myeloid and lymphoid potential. Here we report that whereas IL-10 alone has no ability to stimulate growth of primitive (Lin-Sca-1(+)c-kit+) bone marrow progenitor cells, it potently enhances FL + IL-7-induced proliferation (sevenfold). This enhanced proliferation results from recruitment of progenitors unresponsive to FL + IL-7 alone, as well as from increased growth of individual clones, resulting in a 7,000-fold cellular expansion over 12 days. Single cell cultures and delayed addition studies suggested that the stimulatory effect of IL-10 was directly mediated on the progenitor cells. The cells generated in response to FL + IL-7 + IL-10 appeared to be almost exclusively proB cells, as shown by their expression of B220, CD24, CD43, and lack of expression of c mu, myeloid, erythroid, and T-cell surface antigens. Although IL-10 also enhanced kit ligand (KL) + IL-7-induced proliferation of Lin-Sca-1(+)c-kit+ progenitor cells, the resulting cells were predominantly myeloid progeny. Accordingly, FL + IL-7 + IL-10 was 100-fold more efficient in stimulating production of proB cells than KL + IL-7 + IL-10. In contrast to its ability to stimulate the earliest phase of proB cell formation and proliferation, IL-10 inhibited growth of proB cells generated in response to FL + IL-7. Analysis of CD19 expression on cells generated in FL + IL-7 + IL-10 showed that almost all cells generated under these conditions lacked expression of CD19, in contrast to cells generated in the absence of IL-10, which were predominantly CD19(+). Replating of sorted CD19(+) and CD19(-) proB cells in FL + IL-7 or FL + IL-7 + IL-10 showed that IL-10 efficiently blocked growth of CD19(+), but not CD19(-) cells. Both CD19(-) and CD19(+) cells expressed lambda5 and VpreB , shown to be specific for B-cell progenitors. In addition, sorted CD19(-) cells generated CD19(+) cells in response to FL + IL-7. Thus, IL-10 has a dual regulatory effect on early B-cell development from primitive murine bone marrow progenitor cells in that it enhances FL + IL-7-induced proB-cell formation and growth before acquisition of CD19 expression, whereas growth of CD19(+) proB cells is inhibited.

Animals↗
PubMed1997

Prostaglandins attenuate cardiac contractile dysfunction produced by free radical generation but not by hydrogen peroxide.

The aim of this study was to examine and compare the potential influence of cyclooxygenase or lipoxygenase derived metabolites of arachidonic acid on myocardial injury produced either by a free radical generating system consisting of purine plus xanthine oxidase or that produced by hydrogen peroxide. A free radical generating system consisting of purine (2.3 mM) and xanthine oxidase (10 U/L) as well as hydrogen peroxide (75 microM) produced significant functional changes in the absence of either significant deficits in high energy phosphates or ultrastructural damage. Prostaglandin F2 alpha (30 nM) significantly attenuated both the negative inotropic effect of purine plus xanthine oxidase as well as the ability of the free radical generator to elevate diastolic pressure. An identical concentration of prostaglandin 12 (prostacyclin) significantly reduced diastolic pressure elevation only and had no effect on contractile depression. The salutary effects of the two PGs occurred in the absence of any inhibitory influence on superoxide anion generation produced by the purine and xanthine oxidase reaction. None of prostaglandins modulated the response to hydrogen peroxide. In addition, neither prostaglandin E2 nor leukotrienes exerted any effect on changes produced by either type of oxidative stress. A 5 fold elevation in the concentrations of free radical generators or hydrogen peroxide produced extensive injury as characterized by a virtual total loss in contractility, 400% elevation in diastolic pressure, ultrastructural damage and significant depletions in high energy phosphate content. None of these effects were modulated by eicosanoid treatment. Our results therefore demonstrate a selective ability of both prostaglandin F2 alpha and to a lesser extent prostacyclin, to attenuate dysfunction produced by purine plus xanthine oxidase but not hydrogen peroxide. It is possible that these eicosanoids may represent endogenous protective factors under conditions of enhanced oxidative stress associated with superoxide anion generation.

Animals↗
PubMed1997

Enhanced monocyte generation of reactive oxygen species in primary systemic vasculitis.

OBJECTIVE: Little is known about the role of mononuclear phagocytes in systemic vasculitis. We examined the hypothesis that monocytes from patients with primary systemic vasculitis have increased capacity to generate reactive oxygen species. METHODS: We studied patients with primary systemic vasculitis (n = 24) and compared them with patients with autoimmune related vasculitis (20), peripheral vascular disease (12), and postrenal transplantation (8). Healthy controls were also studied (56). Peripheral blood monocytes were stimulated using phorbol myristate acetate (PMA). We measured the generation of superoxide by cytochrome c reduction and myeloperoxidase (MPO) dependent products using peak luminol chemiluminescence. RESULTS: Patients with primary systemic vasculitis generated significantly more superoxide than all 3 non-vasculitis groups. Superoxide generation in the autoimmune vasculitis group was also higher than other groups but failed to reach significance versus controls (p = 0.07). Generation of MPO dependent products was also significantly higher in patients with primary vasculitis compared to all other groups. Subgroup analysis within the primary vasculitis group showed no correlation of these findings with disease activity, antineutrophil cytoplasmic antibodies, or American College of Rheumatology classification. CONCLUSION: Mononuclear phagocytes act as a source of reactive oxygen species in primary systemic vasculitis. Further study is required to determine if the reactive oxygen species generated act as a mechanism to promote vessel wall injury, or healing in this condition.

Adult↗
PubMed1997

Characteristics of tuberculosis patients who generate secondary cases.

OBJECTIVE: To determine the characteristics of smear positive tuberculosis (TB) patients who generate secondary TB cases. METHODS: Those smear positive TB patients detected by the Barcelona Tuberculosis Program between 1990-1993, and for whom contact studies had been performed, were studied. We analyzed the predictive role of the variables: age, sex, intravenous drug use (IVDU), the presence of the acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection, radiology pattern, district of residence, history of imprisonment, alcoholism, smoking, history of TB, treatment compliance and the number of secondary cases generated. Statistical analysis was based on the logistic regression model, calculating the odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of the 1079 patients studied, 78 (7.2%) had generated only one secondary case, and 30 (2.8%) two or more. The variables associated with generating two or more secondary cases were: IVDU (P < 0.001; OR = 4.06; CI: 1.80-9.15), cavitary radiology pattern (P = 0.002; OR = 3.69; CI: 1.62-8.43), and age (P = 0.016; OR = 0.98; CI: 0.96-0.99). When we examined those who had generated one or more secondary cases, the following variables were significant: IVDU (P = 0.043; OR = 1.75; CI: 1.02-3.02), cavitary radiology pattern (P < 0.001; OR = 3.07; CI: 1.98-4.77) and age (P < 0.001; OR = 0.98; CI: 0.97-0.99). CONCLUSION: The study of the contacts of smear positive TB patients allows us to detect an important number of secondary cases. Young adults, those with cavitary radiology pattern, and IVDU are more likely to generate secondary cases.

AIDS-Related Opportunistic Infections↗
PubMed1997

Features of oligodontia in three generations.

Congenitally missing teeth of three generations of a family and the spousal influence on the oligodontia of the third generation is investigated. For clarification, a review of commonly used terms is included in the paper. Although there are a number of factors affecting the failure to develop permanent tooth buds, most researchers believe that an autosomal dominant trait is responsible for the oligodontia in this family. Many syndromes are associated with oligodontia, but none seem to be prevalent in the direct descendants of the first generation. A member of the second generation married a person with Witkop's (tooth-and-nail) syndrome. Subsequently, their child exhibits the same manifestations. A feature noted in this three generation pedigree is missing permanent first molars. This is considered rare, especially when few abnormal ectodermal findings are reported. Additional findings include an increased number of missing teeth, decreased tooth size and a prominent maxillary labial frenum. The dental treatment for patients affected will likely involve a multidisciplinary approach. The treatment is particularly important since the lack of a full complement of teeth impacts the emotional and physical well-being of the individual. Children who are missing permanent teeth should be screened for other ectodermal abnormalities to rule out syndromes associated with congenitally missing teeth. Oligodontia is predicted to affect fifty percent of the fourth generation. It may vary in penetrance and expression.

Anodontia↗
PubMed1998

Effect of SR121566A, a potent GP IIb-IIIa antagonist on platelet-mediated thrombin generation in vitro and in vivo.

The effect of SR121566A, a new non-peptide GP IIb-IIIa antagonist was studied in vitro with regard to thrombin generation in platelet rich plasma and in vivo on stasis-induced venous thrombosis in the rabbit. SR121566A inhibited ADP-, arachidonic acid- and collagen-induced human platelet aggregation with IC50 values of 46 +/- 7.5, 56 +/- 6 and 42 +/- 3 nM, respectively. In the same experimental conditions, SR121566A strongly inhibited thrombin generation triggered by low concentrations of tissue factor. SR121566A reduced in a dose-dependent manner both the area under the curve and the thrombin peak concentration but did not affect the lag phase (defined as the time until 10 nM thrombin was generated). Aspirin (100 microg/ml) did not affect thrombin generation. One hour after intravenous administration to rabbits, SR121566A exhibited a potent ex vivo inhibitory effect against ADP-, arachidonic acid- and collagen-induced platelet aggregation. The ID50 were 0.6 +/- 0.25, 0.7 +/- 0.08 and 0.13 +/- 0.08 mg/kg, respectively. The ability of aspirin and SR121566A to affect venous stasis was determined in a stasis-induced venous thrombosis model in rabbits under high and low thrombogenic challenges. While aspirin was ineffective in both conditions, SR121566A significantly inhibited thrombus formation under low thrombogenic challenge demonstrating for the first time that a potent non-peptide platelet GP IIb-IIIa antagonist inhibits thrombin generation in vivo and exhibits a strong antithrombotic effect with regard to stasis-induced venous thrombosis. These results therefore confirm the existence of a close relationship between platelet activation and thrombin generation leading to blood coagulation but also emphasise the key role of platelets in the development of venous thrombosis, most likely through activation of the GP IIb-IIIa complex.

Animals↗
PubMedDate not supplied

Accuracy of primary bedside neonatal nurse-generated score for neonatal acute physiology (SNAP) scores.

OBJECTIVE: To determine whether 24-hour SNAP scores generated from data gathered by primary bedside nurses agreed with the SNAP scores of one trained research nurse. STUDY DESIGN: Primary bedside nurses (n = 50) in a level III private nursery collected data necessary for generating 24-hour SNAP scores on 60 consecutively admitted inborn neonates who lived at least 24 hours. The amount of time required for data collection and scoring was also determined. SNAP scores and the time required to generate them were compared with the unit research nurse's SNAP scores and time required to generate them on the same 60 patients. The Wilcoxon rank test and Spearman's rank correlation were used for statistical analyses. RESULTS: SNAP scores generated from primary bedside nursing data did not differ from those of the research nurse's SNAP scores (11.7 +/- 0.8 vs 11.4 +/- 0.9 [mean +/- SEM], p = 0.7), and they correlated well over a wide range of SNAP scores (r = 0.93, p = 0.0001). Primary bedside nurses required more time (15 +/- 0.7 vs 3.0 +/- 0.08 minutes, p = 0.0001) to generate SNAP scores than the research nurse. CONCLUSION: Primary bedside level III nurses can accurately obtain data for SNAP scores during 8- to 12-hour shifts.

Data Collection↗
PubMed1998

Dendritic cells improve the generation of Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of posttransplantation lymphoma.

BACKGROUND: The use of immunosuppressive therapies after solid organ transplantation has been shown to increase a patient's risk for Epstein-Barr virus (EBV)-associated lymphoma. A potential therapy for this disorder is the adoptive transfer of EBV-specific cytotoxic T lymphocytes (CTLs). We proposed that dendritic cells (DCs) could be loaded with EBV antigens and be used to improve the in vitro generation of EBV-specific CTLs. METHODS: Autologous EBV-transformed B-lymphoblastoid cell lines (BLCLs) were generated from normal donors, and CTLs were initiated by culturing peripheral blood mononuclear cells with DCs alone, disrupted BLCLs alone, intact, irradiated BLCLs alone, and DCs loaded with disrupted BLCLs. Lytic activities were determined with a 4-hour chromium-release assay against autologous BLCLs, and statistical calculations were performed by a Student t test assuming equal variance. RESULTS: The lytic activity of CTLs generated with DCs loaded with disrupted BLCLs reached 78% and was statistically significant (P < .01) at all effector/target ratios compared with CTLs generated with DCs alone, disrupted BLCLs alone, or intact BLCLs alone. Total numbers of CTLs were also greater than those of control groups for DCs loaded with disrupted BLCLs. CONCLUSIONS: DCs improved the in vitro generation of EBV-specific CTLs as evidenced by this group's significantly increased lytic activity over that of the control group. The improved lytic activity of DC-generated EBV-CTLs suggests that adoptive transfer of these cells could lead to a more effective immunotherapeutic response against posttransplantation EBV-associated lymphoma.

Antigens, Viral↗
PubMed1998

Generation of CMRF-44+ monocyte-derived dendritic cells: insights into phenotype and function.

The CMRF-44 monoclonal antibody (MoAb) recognizes an intermediate stage of blood dendritic cell (DC) differentiation as well as mature CD83+ blood DC. Here we describe the use of the CMRF-44 MoAb to monitor the in vitro development of DC-like cells from peripheral blood mononuclear cells. Neither granulocyte-macrophage colony-stimulating factor (GM-CSF) nor GM-CSF plus tumor necrosis factor-alpha (TNF-alpha) supported the development of CMRF-44+ cells. However, GM-CSF plus interleukin (IL)-4 generated a substantial number of CMRF-44+ cells among the heterogeneous CD14- myeloid cell population, produced after 7 or 10 days of culture. The addition of TNF-alpha to GM-CSF+IL-4 on the fifth day of culture enhanced the generation of CMRF-44+ cells from days 7 to 14. A concentration of 50 U/mL of IL-4 was sufficient to allow the development of CMRF-44+ cells. The presence of GM-CSF was essential, but a wide range of concentrations (50-800 U/mL) was effective for supporting IL-4-induced generation of CMRF-44+ cells. TNF-alpha at concentrations of 20 or 50 ng/mL induced a maximal increase in the number of CMRF-44+ cells. The CMRF-44+ DCs generated in the presence of GM-CSF+IL-4 were large, irregularly shaped cells with variable CD1a expression and have CD83 transcripts but no CD83 surface expression. Additional TNF-alpha treatment induced prominent dendritic processes and surface expression of CD83 on CMRF-44+ DCs. The CMRF-44+ DCs generated in GM-CSF+IL-4 showed higher allostimulatory activity than CMRF-44 cells but were less efficient at processing and presenting soluble antigen to T-lymphocyte lines. TNF-alpha treatment reduced antigen uptake but increased the allostimulatory activity of CMRF-44+ DCs. CMRF-44+ DC differentiation from blood CD14+ monocytes was not radiosensitive and thus does not involve cell division. We conclude that the MoAb CMRF-44 identifies both intermediate and fully mature stages of monocyte-DC differentiation and may be a useful marker in establishing the optimal timing for antigen loading of in vitro-generated monocyte-derived DCs.

Antibodies, Monoclonal↗
PubMed1998

Force generation simplified. Insights from laser temperature-jump experiments on contracting muscle fibers.

Raising the temperature of a maximally Ca(2+)-activated muscle fiber causes a sigmoidal increase in tension. The kinetics that govern this process can be explored by step-heating the fiber a few degrees with a laser temperature-jump. A biexponential increase in tension results; a third exponential phase that opposes this biphasic rise in tension is only observed when phosphate, a reaction product normally at low concentration, is added to the fiber. This chapter explains how the temperature dependencies of isometric tension and the temperature jump kinetics interrelate, and how these insights have modified and simplified our understanding of current mechanisms of force generation. The fast kinetic phase of the tension rise appears associated with single-step force generation or a power stroke, a process largely isolated from adjacent steps in the crossbridge cycle. The amplitude of the slow phase of the tension rise exhibits a remarkable approximately 1:1 ratio to the amplitude of the fast, tension generating phase above 10 degrees C. The similarity of these two amplitudes, that combine to give the complete rise in isometric tension with temperature, appear to fit a model in which one of a pair of myosin heads generates force while the second head is poised to function after the power stroke of the first has occurred. The phase with the negative amplitude seen with added phosphate points to a mechanism in which phosphate release is indirectly linked to the tension generation by forward flow through the crossbridge cycle to tension generation.

Animals↗
PubMed1976

Fibrinogen and its derivatives: cofactors in the intrinsic generation of thrombin.

The simultaneous additon of suboptimal concentrations of factor VIII and intact or plasmin-lysed fibrinogen into mixtures of the vitamin K dependent factors, phospholipids, adsorbed bovine serum (supplier to factor V) and calcium, increased the amount of thrombin which was generated three to twenty times over the sum of the amounts which were generated when factor VIII, or fibrinogen, or its derivatives were added separately into the thrombin generating mixture. When factor VIII was added together with both fibrinogen and its derivatives, the amount of thrombin generated was even greater, about 130% larger than the amount which was generated in the presence of equal concentrations of only intact fibrinogen plus factor VIII. Addition of albumin instead of fibrinogen or its derivatives has a similar but significantly lower effect on thrombin generation. It appears, therefore, that both intact fibrinogen and its plasminolytic derivatives, singly or in combination, and to a lesser extent albumin, act as cofactors in the reaction which is regulated by factor VIII.

Animals↗
PubMed2006

An improved 62Zn/62Cu generator based on a cation exchanger and its fully remote-controlled preparation for clinical use.

OBJECTIVE: The goal of this study was to develop an improved (62)Zn/(62)Cu generator based on cation exchange resin and remote preparation at high radioactivity scale for clinical use. METHODS: A natural Cu target was irradiated with proton beam in the energy range of 30-->19 MeV at a beam current of 10 muA for 1 h to obtain around 1.7 GBq of (62)Zn. The (62)Zn was isolated from the Cu target on an anion exchange column with more than 97% yield within 2.5 h from the EOB. The (62)Zn/(62)Cu generator was prepared by loading the (62)Zn(2+) on a Sep-Pak plus CM cartridge. RESULTS: The generator showed high elution efficiency ( approximately 96%) using a small volume (ca. 3 ml) of a 200-mM glycine solution with a very low breakthrough of (62)Zn (<0.1%). CONCLUSIONS: This (62)Zn/(62)Cu generator has been proven to be highly useful as a source of (62)Cu for the synthesis of (62)Cu-labeled compounds. The clinical application of [(62)Cu]Cu-ATSM produced with this generator has been already approved by the Institutional Review Board at the National Institute of Radiological Sciences.

Cation Exchange Resins↗
PubMed1999

Manufacture of strontium-82/rubidium-82 generators and quality control of rubidium-82 chloride for myocardial perfusion imaging in patients using positron emission tomography.

We describe a protocol to manufacture 82Sr/82Rb generators and 82RbCl for myocardial imaging with PET. The generators are manufactured in 3 stages: (1) preparation of a tin oxide column, (2) leak test of the generator column and (3) loading of the generator with 82Sr. The generators produced sterile and non-pyrogenic 82RbCl for i.v. injection. No significant 82Sr/85Sr breakthroughs were observed after elution with 20 1 of saline. The automated system delivered human doses of 82RbCl accurately.

Chlorides↗