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PubMedDate not supplied

Interaction between clonal plasma cells and the immune system in plasma cell dyscrasias.

The term "monoclonal gammopathy" (MG) includes a group of clonal plasma cell disorders, which show heterogeneous clinical behavior. While multiple myeloma (MM) and plasma cell leukemia (PCL) are incurable malignant diseases, most patients with MG of undetermined significance (MGUS) show an indolent/benign clinical course. Evidence has accumulated which supports the role of the bone marrow microenvironment in MG. Accordingly, the survival, drug-resistance and proliferation of MM cells have been shown to be largely dependent on a supportive microenvironment. Among the different environment-associated parameters, those related to the status/activity of the immune system are particularly relevant. This review focuses on the different ways clonal plasma cells (PC) interact with the immune system in different models of MG, to characterize crucial events in the development and progression of MG. These advances may support the design of novel therapeutic approaches in patients with MG.

Bone Marrow↗
PubMed1999

Risk of transmission of Creutzfeldt-Jakob disease by transfusion of blood, plasma, and plasma derivatives.

Studies in experimental animals and case-reports of transmission of Creutzfeldt-Jakob Disease (CJD) by blood transfusion or by albumin products have raised the possibility that CJD may be transmitted by transfusion. The risk of transmission of CJD by transfusion remains theoretical, since no confirmed case of CJD has ever been causally attributed to the receipt of a blood transfusion, no confirmed case of CJD has developed in recipients of clotting factor concentrates, and no cluster of CJD cases has been reported following the administration of a pooled plasma derivative to which a donor who subsequently developed CJD had contributed. However, based on a review of the hitherto available data, it is impossible to conclude at this time that CJD is not transmitted by blood or plasma transfusion or by the administration of pooled plasma derivatives. This review discusses the findings of the animal experiments and the human studies that investigated the potential for transmission of CJD among humans by transfusion, and explains the statistical difficulties associated with proving the negative hypothesis that CJD is not transmitted by transfusion.

Blood Component Transfusion↗
PubMed1981

Calculated changes in pH and pCO2 in arterial blood plasma assuming absence of ion and water exchange between plasma and erythrocytes during their equilibration with alveolar gas.

As a contribution to solving the problem of pH disequilibrium in arterial blood, the results of two modes of gas exchange in the lung have been calculated using an equilibrium state model of the blood. In both cases the HCO3-/Cl-exchange was assumed to occur after the gas exchange in the pulmonary capillaries. When the gas exchange was assumed to be dependent on intra-erythrocytic carbonic anhydrase, the plasma pH in the arterial blood increased. When plasma erythrocytes were assumed to equilibrate separately with the alveolar gas due to pressure of extra-erythrocytic carbonic anhydrase, plasma pH in the arterial blood decreased. In each case there was a slight increase in pCO2 after the blood had left the pulmonary capillaries.

Animals↗
PubMed2006

Fresh frozen plasma and platelet concentrates may increase plasma anti-diphtheria toxin IgG concentrations: Implications for diphtheria fusion protein therapy.

We are developing two fusion proteins consisting of a diphtheria toxin (DT) linked to either granulocyte macrophage colony stimulating factor (DT388-GMCSF) or interleukin-3 (DT388-IL3). In trials, patients with anti-DT IgG concentrations >2.5 microg/ml had significantly lower concentrations of either fusion protein. DT389-IL2 is currently FDA approved for the treatment of cutaneous T-cell lymphomas. We noted increased concentrations of anti-DT IgG after administration of platelet concentrates (PC). Because many of these patients require transfusions, we measured the anti-DT IgG content of FFP and PC. We assayed 14 bags of FFP and 12 bags of single-donor PCs for anti-DT IgG by an enzymoimmunoassay against DT389-IL2, DT388-IL3, DT388-GMCSF. The median (percent of samples positive) of anti-DT IgG concentrations in PC against DT388-GMCSF, DT388-IL3, DT389-IL2 was 0.8 microg/ml (83%), 0.7 microg/ml (83%), and 0.3 microg/ml (58%), respectively. The median (percent of samples positive) anti-DT IgG concentration in FFP against DT388-GMCSF, DT388-IL3, and DT389-IL2 was 2.1 microg/ml (86%), 1.9 microg/ml (93%), and 1.4 microg/ml (86%), respectively. There was a strong association between anti-DT389IL2 IgG, anti-DT388IL3 IgG, and anti-DT388GMCSF IgG concentrations in both the FFP (95.6%) and PC (76.3%). Assuming a plasma volume of 3 l in a 70 kg patient, a single FFP unit would increase the plasma anti-DT389IL2 IgG, anti-DT388IL3 IgG, and anti-DT388GMCSF IgG by 0.13 microg/ml, 0.17 microg/ml, and 0.19 microg/ml, respectively. For PC, a single unit would increase plasma anti-DT389-IL2 IgG, anti-DT388-IL3 IgG, and anti-DT388-GMCSF IgG by 0.03 microg/ml, 0.06 microg/ml, and 0.07 microg/ml, respectively. In conclusion, a single FFP or PC appears to minimally increase anti-DT IgG concentrations, but multiple units may significantly do such.

Blood Platelets↗
PubMed1986

Estrogen effects on plasma volume, arterial blood pressure, interstitial space, plasma proteins, and blood viscosity in sheep.

In adult castrated ewes the infusion of 17 beta-estradiol for 3 weeks was associated with a 12% increase in body weight, a 20% increase in whole blood volume (mainly due to a 27% increase of plasma volume), a 13% decrease in mean arterial blood pressure, and a 40% increase in heart rate. The change in plasma volume correlated with the change in estradiol concentration (r = 0.72). Most of the fluid was retained in the interstitial space, as represented by a 6 kg weight gain, 10% of which was in the intravascular compartment. Whole blood and plasma viscosity increased 16% and 21%, respectively, thus reversing some of the blood volume effects toward a hyperdynamic cardiovascular state. We conclude that many of the cardiovascular and hematologic changes with estrogen administration are similar to the changes observed during pregnancy, with the proposed requirement of decrease in mean arterial blood pressure as a condition for blood volume expansion.

Animals↗
PubMed1981

Prospective controlled trial of cryoprecipitated plasma, plasma protein fraction and serum albumin solution for kidney preservation.

A controlled prospective study was conducted to compare the results of kidney preservation and transplantation in regard to the type of perfusate used for perfusion preservation. Cryoprecipitated plasma, plasma protein fraction and serum albumin solution were used as perfusate. Between February 1979 and July 1980, 176 kidneys were preserved by one of these perfusates and transplanted. There was no statistically significant difference in the donor and recipient status, perfusion characteristics or graft and patient survival among the three groups. Synthetic perfusates are an acceptable alternative to cryoprecipitated plasma for perfusion preservation of cadaver kidneys.

Adult↗
PubMed1994

Flow and antibody binding properties of hydrated fibrins prepared from plasma, platelet rich plasma and whole blood.

Previous studies, using cross-linked fibrin prepared from purified fibrinogen, showed low binding of a fibrin-specific monoclonal antibody designated T2G1 (Procyk et al., Blood 77:1469-75, 1991). In this study we investigated the binding of T2G1 and one other antibody to clots prepared from platelet poor plasma (PPP), platelet rich plasma (PRP) and whole blood. In contrast to our previous study, we used unlabelled antibodies and quantitated the level bound by ELISA, measuring antibody concentration in the non-adsorbed fraction. Antibody T2G1 bound 1.35 +/- 0.10 pmol/pmol fibrin (n = 11) to whole blood columns, 1.64 +/- 0.18 (n = 10) to PRP columns and 1.58 +/- 0.13 (n = 8) to PPP columns. The binding of T2G1 to columns made from purified fibrinogen was 0.78 +/- 0.05 pmol/pmol fibrin (n = 15). An antibody to a conformation-dependent epitope on Fragment D (Fd4-7B3) bound in comparable amounts to the different fibrins. Flow data show that whole blood columns, and also, but to a lesser extent those made with plasma, had a higher flow rate, permeability and fiber mass-length ratio than columns prepared from fibrinogen indicating a more coarse fibrin network. These data show that the presence of other proteins and blood cells, similar to what might occur in vivo, not only lead to an increase in the permeability of gels but also allow for better exposure of some epitopes.

Antibodies, Monoclonal↗
PubMed2006

Clinical use of plasma and plasma fractions.

The use of plasma and plasma-derived products has always involved a careful balance of anticipated benefit versus risk. Risk reduction through pathogen-inactivated products has been successful, but the expense of manufacture does not warrant widespread use. Although plasma has always had limited indications for use, these are often misunderstood or ignored in favor of received knowledge and tradition. Solid evidence from multiple trials support the limited indications for FFP described here and support products that target specific coagulation defects.

Blood Coagulation Factors↗
PubMed2005

Stability of solvent/detergent-treated plasma and single-donor fresh-frozen plasma during 48 h after thawing.

The aim of this study was to compare the quality of solvent/detergent (SD) treated plasma, Octaplas, and single-donor fresh-frozen plasma (FFP) units during 48-h storage after thawing. Octaplas bags of different blood groups and individual FFP units were thawed and stored at either +4 degrees C or at room temperature (RT) for 48 h. Samples drawn during the observation period were investigated on various coagulation factor and protease inhibitor activities using standard coagulation and chromogenic assays. The generation of FVIIa was followed as a marker of coagulation factor activation. All investigated coagulation factors and protease inhibitors were stable for at least 8h during storage of Octaplas at +4 degrees C. FVIII levels started to decline earlier in FFP than in Octaplas at both storage temperatures. Stored Octaplas OD660 values were more stable during the storage period than FFP OD660 values, whereas VWF multimeric patterns were comparably stable in both types of plasma. In conclusion, this stability study has demonstrated that thawed Octaplas maintains its high quality, even with a time safety margin, for 8 h at +4 degrees C and for 6 h at RT. In general, there was more variability in coagulation factor levels among different FFP units compared with different Octaplas batches.

Blood Coagulation Tests↗
PubMed1982

The effect of dialysate sodium concentration on body fluid compartment volume, plasma renin activity and plasma aldosterone concentration in chronic hemodialysis patients.

Six stable chronic hemodialysis patients received six hemodialysis treatments: two each with the dialysate sodium concentration (DNa) 7% greater than serum sodium concentration, two with a DNa equal to serum sodium concentration and two with the DNa 7% less than the serum sodium concentration. During one treatment with each dialysate 2 kg of fluid was removed and during the other treatments the patient's weight was kept constant. Total body water (TBW), intracellular water (ICW), extracellular water (ECW), plasma volume (PV), plasma renin activity (PRA), aldosterone (ALDO), Na, BUN and osmolality were determined before and after each treatment. Fluid removal during dialysis had no effect on ICW with essentially all the fluid removed during dialysis coming from ECW. ICW increased with low DNa and decreased with high DNa. The effect of DNa on ECW and PV was the opposite of that on ICW. PRA increased and ALDO decreased during dialysis. Predialysis ALDO directly correlated with PRA (r = 0.68, p less than 0.001) but not with serum potassium concentration. Post dialysis ALDO was not significantly correlated with either PRA or potassium. Fluid removal and low DNa increased both PRA and ALDO. These studies indicate that water shifts from the extracellular space into intracellular space when DNa is lower than serum Na and the reverse is true when DNa exceeds serum Na. Plasma aldosterone decreases during dialysis despite an increase in PRA, possibly related to the decrease in serum potassium concentration. The effect of fluid removal and low DNa on PRA and ALDO may be related to a reduction in ECW and/or PV.

Adult↗
PubMed1994

The effect of methylene blue phototreatment on plasma proteins and in vitro coagulation capability of single-donor fresh-frozen plasma.

BACKGROUND: Photodynamic virus inactivation of fresh-frozen plasma (FFP) may result in its impaired coagulation capability. STUDY DESIGN AND METHODS: Double-volume plasmapheresis samples from 11 donors were divided in pairs of 250 mL. One group underwent methylene blue (MB) phototreatment (MB-FFP). The other group was treated according to the standards of the American Association of Blood Banks for preparation and storage of FFP. Parameters of hemostasis and clinically important plasma proteins were tested in native plasma, thawed MB-FFP, thawed FFP, and twice-frozen and thawed FFP (FFP-II). RESULTS: Mean activities of factor V (73.4 vs. 94.5%; p < 0.01), factor VIII (58.1 vs. 86.7%; p < 0.001), and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) were reduced in MB-FFP as compared to those in FFP. The comparison of MB-FFP to FFP-II revealed reduced activities of factor VIII (58.1 vs. 85.2%; p < 0.001) and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) but no changes in factor V. Activated partial thromboplastin time in MB-FFP was prolonged beyond the upper normal range (+5.3 sec; p < 0.001) and prothrombin time increased in MB-FFP versus FFP (+0.96 sec; p < 0.001). CONCLUSION: MB phototreatment reduces the in vitro coagulation capacity of FFP, most likely as a result of the effects of an additional freezing and thawing procedure and photooxidation-induced protein damage.

Blood Coagulation↗
PubMed2000

Radioimmunoassays for bull seminal plasma proteins (BSP-A1/-A2, BSP-A3, and BSP-30-Kilodaltons), and their quantification in seminal plasma and sperm.

Three proteins, BSP-A1/-A2, BSP-A3, and BSP-30 kilodaltons (collectively called BSP proteins), represent the major proteins of bovine seminal plasma (BSP). At ejaculation, these proteins bind to the sperm surface and induce molecular changes in the plasma membrane that are deemed to be essential for sperm capacitation. The present study was carried out to develop specific radioimmunoassays (RIAs) for the quantification of each of the BSP proteins in BSP and sperm. RIAs were developed using polyclonal antibodies raised in rabbits against each BSP protein. The purified and iodinated BSP proteins were used as standard and tracer, respectively. The RIAs that were developed were shown to be specific for each protein and the cross-reactivity toward various antigens was negligible (<2%). The average sensitivity limit was 5 ng/ml of sample for BSP-A1/-A2 and BSP-A3, and 40 ng/ml of sample for BSP-30-kDa. The concentration of BSP proteins was determined by analyzing the RIA data with spline function. BSP proteins represented 40% to 57% of seminal plasma total protein (25% to 47% of BSP-A1/-A2, 3% to 5% of BSP-A3, and 3% to 7% of BSP-30 kDa) and 4% to 6% of sperm total protein (2.5% to 4% of BSP-A1/-A2, 0.4% to 0.9% of BSP-A3, and 0.5% to 1% of BSP-30-kDa). We also determined the concentration of BSP proteins that were sperm-bound after semen cryopreservation in Tris-egg yolk-glycerol extender. A significant decrease (70%-80%) in sperm-bound BSP proteins was noted after cryopreservation. The availability of reliable RIA procedures should aid in the further understanding of the role of BSP proteins in sperm function as well as their effect on sperm cryopreservation.

Animals↗
PubMed1981

Axial changes of blood and plasma flow, pressure, and cellular deposition in capillary plasma filters.

The ability to separate plasma on-line from whole blood by membranes has generated interest in applying this process to source plasma collection and to the therapeutic treatment of various disease states. The availability of capillary membrane devices in particular has prompted investigations in these areas. The deposition of blood cellular elements has required the investigation of those parameters related to fluid and mass flux. Analytical solutions relating blood flow rate, filtration rate, and pressure and deposition with respect to axial distance have been obtained. Comparison of these solutions with preliminary experimental results have been made. Results indicate that the deposition parameter versus distance from the inlet is a very sensitive function of capillary membrane properties and operating conditions. Plasma fluxes are also highly dependent on blood, membrane, and filter properties and operating conditions.

Blood↗
PubMed1985

Acute effect of plasma exchange on arterial blood pressure and plasma renin activity.

Blood pressure (BP) decreases significantly in patients with immune complex nephritis and hypertension in the course of therapeutic plasma exchange (TPE). To investigate possible underlying mechanisms of this effect, the variations of supine and upright BP and plasma renin activity (PRA) acutely induced by PE (performed by isovolumetric replacement of plasma with 4% albumin in saline solution) were analyzed in six patients. On the average, both supine and upright BP decreased after TPE; however, statistical significance was obtained only for upright systolic BP. Supine and upright PRA did not change significantly, although a clearly blunted response to posture was observed in three patients. The changes of BP induced by TPE were apparently not due to a functional depression of the renin-angiotensin system, since the more marked decrements in BP were observed in the patients with lower basal PRA.

Adolescent↗
PubMed2005

The quality of plasma collected by automated apheresis and of recovered plasma from leukodepleted whole blood.

BACKGROUND: There exists a current lack of information about the composition of the different types of plasma. No direct comparisons between apheresis plasma (AP) and recovered plasma (RP) derived from in-line-filtered whole blood (WB) have been published to date. STUDY DESIGN AND METHODS: Sixty AP units, 100 RP units from in-line-filtered WB held for 3 hours at 20 degrees C between donation and freezing, and an additional 100 RP units held for 15 hours at 20 degrees C before freezing were analyzed for coagulation factors and inhibitors, total protein, immunoglobulin G (IgG), and hemostasis and proteolysis activation markers. The influence of twice freezing and thawing on clotting factors V, VIII, and XI was also examined. RESULTS: AP contains substantially greater activities of factor (F) V, FVIII, F IX, and FXI than RP frozen within 3 hours after WB donation. Prolonged holding of RP at 20 degrees C for more than 15 hours caused an additional reduction in FVIII, FXI, and protein S activities. Significantly greater levels of prothrombin fragments 1 and 2, platelet factor 4, and neutrophil elastase were found in RP compared with AP. IgG was lower in AP compared with RP. Twice freezing and thawing caused a marked drop in FV, FVIII, and FXI activity. CONCLUSION: Higher FVIII and F IX potencies in AP compared with RP can be expected to result in greater yields when used for purification of these clotting factors. AP is presumably more efficient than RP for treating coagulopathies. RP, however, may contain higher IgG levels than AP.

Adult↗
PubMed1985

Pregnancy-associated plasma protein-A and placental protein 5 in human seminal plasma.

Human seminal plasma contains two glycoproteins which are physiochemically and immunologically indistinguishable from pregnancy-associated plasma protein-A and placental protein 5. Seminal concentrations of both glycoproteins did not correlate with clinical assessment of semen quality. Furthermore, analysis of split ejaculates indicated a nontesticular origin for both proteins, which are possibly secreted into the distal portions of the tract by the accessory glands (prostate gland and seminal vesicles). The physiological significance of these findings has yet to be determined. However, it is suggested that pregnancy-associated plasma protein-A, a known potent inhibitor of leukocyte elastase, protects the deposited sperm against proteolytic attack originating from the localized leukocyte reaction within the female reproductive tract, thus contributing towards sperm survival within this immunologically hostile environment and enabling fertilization to occur.

Drug Stability↗
PubMed2005

Discordance between viral loads determined by Roche COBAS AMPLICOR human immunodeficiency virus type 1 monitor (version 1.5) Standard and ultrasensitive assays caused by freezing patient plasma in centrifuged becton-dickinson vacutainer brand plasma preparation tubes.

The Roche COBAS AMPLICOR human immunodeficiency virus type 1 (HIV-1) Monitor (version 1.5) standard and ultrasensitive viral load assays often gave discordant results, with viral loads from the standard assay exceeding those from the ultrasensitive assay by more than 0.5 log(10) for approximately 20% of specimens received. We began studies to determine the extent, magnitude, and reproducibility of the discordance between the assays and to discover and eliminate the cause of this discordance. Until then, we revised our standard operating procedure to include both standard and ultrasensitive testing on all specimens submitted for viral load determinations. Discordant results usually recurred on retesting. They were most prevalent for specimens with ultrasensitive viral loads of <1,000 and rare for specimens with viral loads of >10,000. Often, standard assay results exceeded those of the ultrasensitive assay by 50- to 100-fold. At higher viral loads, the difference between the standard and ultrasensitive assays persisted, but the percent difference was smaller and rarely caused discordance. The proportion of discordant results was significantly higher in specimens from pediatric patients than in specimens from adults. The ultrasensitive viral load determinations generally agreed with the results of the B-DNA (Bayer) viral load assays. If the plasma was transferred from the centrifuged plasma preparation tubes before freezing, standard and ultrasensitive results were concordant with each other and with values determined on plasma from lavender-topped EDTA tubes.

Adolescent↗
PubMed1982

Plasma prostaglandins PGE2 and PGF2 alpha, total effective vascular compliance and renal plasma flow in essential hypertension.

Plasma prostaglandins PGE2 and PGF2 alpha, cardiac hemodynamics, total effective vascular compliance, plasma (PV), interstitial (IFV) and extracellular fluid volumes, and renal indices were determined in 13 men with either borderline or sustained essential hypertension. PGE2 measured in the central venous blood was increased in borderline and in sustained hypertensives (p less than 0.01), while PGF2 alpha remained within normal ranges. Pulmonary degradation of both prostaglandins was decreased. In the overall population, the PGE2/PGF2 alpha ratio was: (i) negatively correlated with central venous pressure (r = -0.68; p less than 0.01), and (ii) positively correlated with total effective vascular compliance (r = 0.76; p less than 0.001), the PV/IFV ratio (r = 0.63; p less than 0.02) and the renal plasma flow (r = 0.79; p less than 0.001). The study suggests that, in hypertensive patients, prostaglandins PGE2 and PGF2 alpha play an important role on the compliance of the venous system and on the control of renal blood flow, contributing to the autoregulatory mechanisms of the hypertensive vascular disease.

Adolescent↗