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PubMed1978

Developmental changes in testicular gonadotropin receptors: plasma gonadotropins and plasma testosterone in the rat.

The relationships between plasma gonadotropins, testicular gonadotropin receptors, and plasma testosterone were examined during neonatal life and throughout sexual maturation in the rat. The binding affinity of testicular LH receptors (2.4 X 10(10) M-1) was significantly higher than that of FSH receptors (2.1 X 10(9) M-1) at all stages of development. The concentration of FSH receptors in the testis reached a peak between 10-15 days of age, then fell to a constant level from 25-90 days. However, the testis content of FSH receptors increased continually with age and reached a plateau at day 60. Plasma FSH declined after birth to a nadir at 15 days, then rose rapidly to a peak at day 38, and fell to a plateau from day 50 through adult life. In contrast to the rapidly changing profile of plasma FSH during early maturation, alterations in plasma LH were less marked throughout development. Although a progressive rise in plasma LH concentration was observed between days 36-51, the simultaneous changes in testicular LH receptors and plasma testosterone were much more prominent. Testicular LH receptors showed a continuous increase in concentration and total number with advancing age and testis growth. The major rise in LH receptor concentration occurred between 15-38 days age, at the same time as the rise in plasma FSH concentration and the phase of rapid testicular growth. Plasma testosterone fell during the 8th-24th days after birth, then rose rapidly between days 35-55. The pubertal rise in plasma testosterone occurred about 15 days after testicular LH receptors began to increase and was coincident with the continuing rise in LH receptor content from day 35 until day 55 and with the progressive increase in plasma LH during this period. These observations have demonstrated that the early development of testicular FSH receptors in followed by a prominent rise in plasma FSH, with concomitant increases in testicular growth and LH receptor concentration. The resulting increase in gonadal sensitivity to LH could be responsible for the marked increase in secretion of testosterone which occurs during puberty in the presence of a relatively small change in the circulating LH concentration. The sequence of changes observed in gonadotropins and their testicular receptors is consistent with the view that FSH-induced testicular sensitivity to LH is an important factor in sexual maturation in the male rat.

Aging↗
PubMed1998

Relationship between plasma adrenocorticotropin, hypothalamic opioid tone, and plasma leptin.

The purpose of the present study was to further the understanding of the relationship between plasma leptin concentrations, hypothalamic opioid tone, and plasma ACTH secretory dynamics. ACTH(1-24) challenges (250 micrograms) produced the expected increase in plasma cortisol levels but did not alter plasma leptin levels. Activation of the entire hypothalamic-pituitary-adrenal (HPA) axis was induced by employing the opioid receptor antagonist, naloxone. By blocking opioidergic inhibitory input to hypothalamic CRH neurons, naloxone induced the expected increase in plasma ACTH and cortisol. Plasma ACTH levels peaked 30 min after naloxone administration, whereas plasma cortisol levels peaked 60 min after opioid receptor blockade. Once again, plasma leptin concentrations were not altered by this manipulation. However, there was a positive correlation between fasting, integrated plasma leptin concentrations, and plasma ACTH responses to naloxone (peak r = 0.822, P < 0.0001; and area under curve r = 0.832, P < 0.0001). The correlation was stronger when leptin was normalized to body mass index and expressed as the leptin/body mass index ratio (peak r = 0.878, P < 0.00001; and area under curve r = 0.882, P < 0.00001). In summary, these findings indicate that activation of the HPA axis does not acutely alter plasma leptin concentrations. However, plasma leptin levels may influence hypothalamic opioidergic tone and thus modulate the magnitude of CRH release. The acute interaction of the HPA axis and leptin is unidirectional.

Adolescent↗
PubMed1975

Application to a radioimmunoassay for angiotensin I to the measurement of plasma renin in rabbits, and comparison with a biological assay of plasma renin activity.

A radioimmunoassay method for ileu-5-angiotensin I was applied to the measurement of plasma renin in rabbits. In the present method, the volume of plasma sample, required for the determination of plasma renin activity and plasma renin concentration, could be reduced to 0.6 ml and 0.05 ml, respectively. A satisfactory correlation (r = 0.918) was found between the plasma renin activity measured by our bioassay method reported previously and that by the present radioimmunoassay method in each of 25 different plasma samples. A highly significant correlation (r = 0.968) was also observed between the plasma renin activity and the plasma renin concentration, both of which were measured by radioimmunoassays, as far as renin concentration remained under 200 ng/ml/hr. On the other hand, the present results appear to indicate that, when a high plasma renin activity was obtained, it was difficult to evaluate the actual plasma renin concentration. Therefore, it would be necessary to be cautious to apply the method for plasma renin activity on the renin rich plasma.

Angiotensin II↗
PubMed1982

Assessment of renal function from plasma urea and plasma creatinine in children.

The diagnostic value of plasma urea and plasma creatinine, used separately and in combination, for assessment of renal function in children was determined from simultaneously measured values of plasma urea, plasma creatinine and glomerular filtration rate (GFR) in 357 children with different nephro-urological disorders. GFR was determined from the total [51Cr]EDTA plasma clearance measured by a reliable single injection method. Four levels of renal function (with the limits expressed as % of the age-dependent normal mean standard GFR) were defined: normal (greater than 75%); moderately decreased (75-52%); considerably decreased (51-28%); and severely decreased (less than 28%). Plasma concentrations of urea (mmol/l) and creatinine (expressed as a percentage of age-dependent normal mean value) were graded into low and high normal, moderately increased, considerably increased and severely increased values. Only by using plasma urea and plasma creatinine in combination all four levels of renal function could be predicted in the individual child with a high degree of certainty (probability 0.94-1.00). The results of the study indicate that the plasma concentration of urea and creatinine should be measured simultaneously, the results being used in combination with due consideration to the variability of plasma creatinine with age. By this procedure the majority of children, i.e. approximately 80%, with nephro-urological disorders who are referred to a paediatric clinic can have their level of renal function predicted with a high degree of certainty. Using plasma urea and plasma creatinine separately the corresponding figure is 50 and 60%, respectively.

Adolescent↗
PubMed1989

Isotopic estimation of plasma glucose conversion to plasma lactate using [6-3H]glucose and [6-14C]glucose.

To determine whether [6-3H]glucose could be used to quantitatively estimate the rate of plasma glucose conversion to plasma lactate, we compared the relative transfer of [3H] and [14C]plasma glucose to plasma lactate in nine postabsorptive anesthetized rats infused to isotopic steady state with [6-3H]glucose and [6-14C]glucose. Glucose turnover (mumol/kg/min) measured with [6-3H]glucose (29.4 +/- 1.7) and [6-14C]glucose (25.0 +/- 1.5), Cori cycle activity (4.35 +/- 0.79), and the percentage of plasma lactate derived from plasma glucose calculated from 14C-specific activities (59.8 +/- 5.8) were all comparable to previously reported values for the overnight fasted rat. Although the percentage of plasma lactate derived from plasma glucose calculated from 3H-specific activities (30.0 +/- 3.3) was only half that calculated from 14C-specific activities (P less than 0.001), the 3H:14C ratios were constant over a wide range of percentage of lactate derived from glucose (r = 0.95, P less than 0.001). We conclude that 3H-specific activity ratios of plasma lactate to plasma glucose cannot be directly used as a quantitative estimate of the percentage of plasma lactate derived from plasma glucose; however, correction for the apparent constant proportionality of detritiation of lactate relative to 14C loss could permit use of [6-3H]glucose for this purpose.

Animals↗
PubMed1975

Plasma aldosterone in anephric and non-nephrectomized dialysis patients in relation to changes in plasma potassium without change in total potassium balance.

Plasma aldosterone concentration has been measured in 13 patients on regular hemodialysis, 7 anephric and 6 non-nephrectomized, following infusion of insulin-glucose. In all patients the plasma potassium fell about 16% within the first 60 min after the infusion, increasing again to about preinfusion levels within 180 min. All anephric patients showed a very low preinfusion value for plasma aldosterone (mean 33.3 pg/ml plasma), which increased significantly (p less than 0.01) after the infusion of insulin-glucose, to about 180% of the initial values, simultaneously with the fall in plasma potassium concentration. A significant inverse correlation (p less than 0.01) was found between changes in plasma aldosterone and potassium. The preinfusion in plasma aldosterone values were significantly higher (p less than 0.01) in the non-nephrectomized than in the anephric group--but of a wide range (26-700 pg/ml plasma). In this group the mean plasma aldosterone concentration showed a significant fall simultaneously with the fall in plasma potassium concentration, but with great variations between patients. There was a significant positive correlation (p less than 0.005) between the changes in plasma aldosterone and potassium. These studies indicate an extremely sensitive regulation of plasma aldosterone secretion in anephric patients, in all probability positively correlated to changes in intracellular adrenal potassium concentration.

Adult↗
PubMed2005

Effects of total plasma protein concentration on plasma sodium, potassium and chloride measurements by an indirect ion selective electrode measuring system.

OBJECTIVE: Ion selective electrodes (ISE) measure electrolytes by two different technologies, direct and indirect. We wished to investigate the effect of total plasma protein concentration on the plasma sodium, potassium and chloride measurements by indirect ISE compared with measurements by direct ISE. METHODS: The evaluation of the objective was performed in a tertiary care hospital on patient blood samples sent to the pathology laboratory for general chemistry analysis. To determine the degree of difference between the two ISE measurements, 195 lithium heparin plasma samples were measured and the results were separated into three groups (65 samples in each group) depending on the protein concentration (e.g. total plasma protein concentration less than, greater than and within the reference range between 62-83 g/L). The samples were analysed over a 40 day period on a Hitachi Modular ISE system - indirect ISE (Roche Australia) and Bayer Rapidlab 865 Blood Gas Analyser - direct ISE (Bayer Diagnostics, Australia). RESULTS: Using indirect ISE, low plasma protein concentrations caused a 'pseudohyper' effect in all 3 analytes and a 'pseudohypo' effect with high plasma protein concentrations. The variation in total protein concentration had the greatest effect on plasma sodium measurement. The relationship was non-linear and no accurate predictive value could be calculated for the plasma electrolytes with changes in plasma protein concentrations. CONCLUSIONS: The plasma sodium, potassium and chloride measurements are effected by changes in plasma protein concentration when measured by indirect ISE systems. Clinicians must be aware that differences exist between the ISE technologies and in border-line clinical situations, the direct ISE systems provide a more accurate estimate of plasma sodium, potassium, chloride, anion gap, osmolality and strong ion difference calculations, and should be used for clinical decision-making.

Journal Article↗
PubMed1991

Contribution of glucose tolerance and plasma insulin levels to the relationships between body fat distribution and plasma lipoprotein levels in women.

Numerous interrelated metabolic and morphological variables such as plasma insulin levels, glucose tolerance and abdominal obesity are associated with changes in plasma lipoprotein levels. The present study was undertaken to differentiate, using a multivariate approach, the respective contributions of plasma glucose and insulin levels, obesity and regional adipose tissue distribution to the variance in plasma lipoproteins. The study group was composed of 69 healthy premenopausal women (age 35.4 +/- 5.0 years (mean +/- s.d.); percent body fat 40.7 +/- 10.1). Indices of carbohydrate metabolism showed significant univariate correlations with triglyceride (TG) and/or cholesterol (CHOL) content of plasma VLDL, LDL and HDL (P less than 0.05). Multivariate analyses indicated that the explained variance in plasma VLDL-TG (R2 x 100 = 44 percent, P less than 0.05) and LDL-apoprotein (apo) B levels (R2 x 100 = 33.1 percent, P less than 0.08) was entirely accounted for by indices of carbohydrate metabolism and body fat distribution, whereas total body fatness added no significant contribution to these models. Multivariate analyses also revealed that the best possible regression model to predict the variation in plasma HDL2-CHOL levels only included computed tomography-derived deep abdominal adipose tissue area (P less than 0.0001). All other variables were unable to further improve the explained variance in plasma HDL2-CHOL levels. In partial correlation analyses, indices of carbohydrate metabolism and the waist-to-hip circumference ratio (WHR) remained significantly correlated with plasma VLDL-TG and LDL-apo B levels after adjustment of VLDL-TG and LDL-apo B for either insulin and glucose levels, or for the WHR (P less than 0.08). After correcting for deep abdominal fat accumulation, no significant correlation was observed between indices of carbohydrate metabolism and plasma HDL2-CHOL levels whereas deep abdominal fat showed significant correlations with HDL2-CHOL levels (P less than 0.05) after correction for indices of carbohydrate metabolism. These results suggest that both disturbances in glucose-insulin homeostasis and abdominal obesity are significantly associated with changes in plasma VLDL-TG and LDL-apo B levels and that these associations are partly independent from each other. These results also indicate that mechanisms other than disturbances in glucose homeostasis and hyperinsulinemia are responsible for the association between the level of deep abdominal fat and plasma HDL2-CHOL levels.

Abdomen↗
PubMed1989

Relation of high plasma triglyceride levels associated with obesity and regional adipose tissue distribution to plasma lipoprotein-lipid composition in premenopausal women.

Abdominal obesity is associated with high plasma triglyceride (TG) and with low plasma high density lipoprotein (HDL)-cholesterol (CHOL) levels. As plasma TG and HDL-CHOL are negatively correlated, the associations between obesity, the regional distribution of body fat, plasma TG levels, and plasma lipoprotein concentration and composition were studied in a sample of 76 premenopausal women (52 obese and 24 non-obese). Obese women had significantly higher plasma levels of VLDL-TG, low density lipoprotein (LDL)-CHOL, LDL-TG, LDL-apolipoprotein (apo) B and reduced HDL-CHOL levels compared to non-obese controls (p less than 0.01). However, plasma concentrations of HDL-apo A-I and HDL-TG were not different between obese and non-obese women. Partial correlation analyses revealed that both fat mass and abdominal fat accumulation significantly contributed to VLDL-TG and HDL-CHOL variances. After control for body fat mass, the waist-to-hip circumference ratio (WHR) remained significantly correlated with plasma LDL-apo B levels and with the LDL-apo B/LDL-CHOL ratio (0.01 greater than p less than 0.05). Body fat mass was, however, associated with TG enrichment of LDL (p less than 0.01). After control for WHR, body fat mass showed no significant association with plasma HDL-TG levels, whereas the WHR was positively correlated with HDL-TG levels (p less than 0.05). Partial correlation analyses indicated that adjustment for fat mass or for the WHR failed to eliminate the associations between plasma VLDL-TG levels and lipoprotein lipid composition. This study emphasizes the importance of plasma VLDL-TG level as a correlate of plasma LDL and HDL lipid composition in abdominal obesity.

Adipose Tissue↗
PubMed1983

Increases in plasma kallikrein-like and pancreas kallikrein-like substances after administration of pancreas or plasma kallikrein.

Differences between the concentration of a kallikrein-like substance in blood obtained by the peptide-MCA method and that obtained by the TAME (N-tosyl-l-arginine methyl ester) method by administering pancreas kallikrein to rabbits have been recognized already and the existence of a Substance X was evaluated. In the present study, it was revealed that administration of pancreas kallikrein resulted in inactivation of kallikrein in the substrate in gut homogenates and homogenates of various organs except for the pancreas. In the pancreas homogenate, inactivation was not observed. On the other hand, there was a possibility that at least part of Substance X existed due to plasma kallikrein. Thus, the concentration of plasma kallikrein in plasma after administration of pancreas kallikrein was determined. A pattern similar to the concentration curve of Substance X was obtained. Thus, it was clarified that plasma kallikrein-like substance, at least, increased when pancreas kallikrein was administered. On the contrary, when plasma kallikrein was administered to the rabbit duodenum, the concentration of pancreas kallikrein-like substance in plasma increased. It was also clarified that plasma kallikrein-like substance increased in vitro by adding pancreas kallikrein to the blood or plasma, whereas the in vitro addition of plasma kallikrein to the blood induced its decomposition and a slight increase in pancreas kallikrein-like substance, and the addition of plasma kallikrein to the plasma induced an increase in plasma kallikrein and a slight increase in pancreas kallikrein-like substance.

Animals↗
PubMed1976

Biologically active luteinizing hormone (LH) in plasma. 1. Validation of the in vitro bioassay when applied to plasma of women.

A recently described in vitro bioassay method for the measurement of biologically active LH (Van Damme et al. 1974) has been applied to the plasma of normally menstruating and post-menopausal women. The specificity of the procedure was established according to the following evidence: 1. Parallelism was observed between dose response curves obtained with serial dilution of a standard LH preparation (HMG 2nd IRP) and plasma pools collected during the follicular phase, at the LH-peak, during the luteal phase and after menopause. 2. There was no evidence for the presence of any synergistic or antagonistic factor in the various plasma specimens. The assay design used to establish this consisted of assaying the standard and plasma pool separately and then together as a mixture followed by an assessment of the difference (if any) in the potencies obtained. Strict additivity should yield a relative potency of 1.0. Plasma pools which were obtained every 2-3 days throughout the menstrual cycle were assayed using this design against the standard (HMG 2nd IRP) and against a mid-cycle plasma pool obtained at the time of the LH-peak. The latter was also assayed against partially purified plasma fractions obtained from a post-menopausal plasma pool after gel filtration and isoelectric focusing. With the exception of 3 assays, in which the estimates of relative potency were 0.91, 0.94 and 0.95, respectively, in 19 assays of additivity, the fiducial limits always included unity. 3. Non-detectable LH levels were found in the plasma or serum of either hypophysectomized or hypopituitary hypogonadal men or women treated with oestrogen/progestogen combined pills. 4. The presence of calf of human serum in the assay medium is an essential requirement for a valid comparison of standard and unknown preparations. In their absence, non-parallel dose response curves between plasma and stardard were obtained. The other established criteria of reliability (sensitivity and precision) were also examined. The method is sufficiently sensitive (3.5-8.0 mIU/ml plasma; HMG (2ng IRP) as standard) for the measurement of LH throughout the cycle. The mean index of precision (gamma) in 230 multiple assays was 0.040. It is concluded that the modified bioassay yields valid and reliable estimates of LH when applied to human plasma obtained throughout the menstrual cycle and after menopause.

Biological Assay↗
PubMed1992

Inhibition of prekallikrein activation in human plasma by components of bovine plasma.

Contact of plasma with a negatively charged surface activates prekallikrein and factor XII reciprocally. Activation of prekallikrein by several activators was impaired in bovine plasma when compared to that in human plasma. The activated partial thromboplastin time of bovine plasma, induced by several activators, was significantly longer than that of human plasma. Cleavage of [125I]factor XII was optimum at 10 min in human plasma but took up to 60 min in bovine plasma. Addition of bovine plasma to human plasma caused significant inhibition of dextran sulfate-induced prekallikrein activation, indicating that the impaired rate of contact activation in bovine plasma is due to the presence of inhibitors. The inhibitory effect was greater at lower concentrations of dextran sulfate but could not be abolished by increasing the concentration. The inhibitory activity eluted in two peaks at low and medium salt concentrations on carboxymethyl ion-exchange chromatography of bovine plasma.

Animals↗
PubMed1976

Changes of plasma volume and plasma composition in water-deprived rats.

Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.

Animals↗
PubMed2002

Manufacture and composition of fresh frozen plasma and virus-inactivated therapeutic plasma preparations: correlation between composition and therapeutic efficacy.

The clinical efficacy of the therapeutic plasma used in the treatment of congenital and acquired severe coagulopathy depends on the potency of clotting factor and inhibitor activities. The composition of plasma strongly depends on the conditions under which it is produced. A low citrate anticoagulant-to-blood ratio, short intervals between donation and plasma separation and rapid freezing markedly improve the preservation of unstable coagulation factors. The influence of different leukocyte reduction filters on plasma quality still requires clarification. Recent trials on long-term storage conditions suggest that keeping plasma at -30 degrees C or colder over a period of 24-36 months prevents substantial decrease in clotting factor activities including factor VIII (FVIII). Three types of therapeutic plasma are currently available. Quarantine-stored fresh frozen plasma (FFP) contains physiological activities of therapeutically relevant plasma proteins, but carries a risk of transmitting blood-borne viruses that cannot be detected by human immunodeficiency virus (HIV) and hepatitis B and C screening. In contrast, solvent/detergent-treated plasma (SDP) and methylene blue/light-treated plasma (MBP) is virtually free of HIV and hepatitis C virus (HCV) subtypes. Virus inactivation procedures can have the consequence of reducing several clotting factors and inhibitors in SDP and MBP to varying degrees. However, pooling of plasma units before solvent/detergent (SD) treatment results in well-standardized protein levels of SDP. At least five prospective trials and four observational studies covering different clinical settings suggest that SDP and FFP do not substantially differ in their clinical efficacy or in their tolerance. By way of contrast, there is a lack of data about the clinical efficacy and tolerance of MBP compared to FFP.

Blood Coagulation Factors↗
PubMed1983

Human seminal plasma contains a protein that shares physicochemical, immunochemical, and immunosuppressive properties with pregnancy-associated plasma protein-A.

Pregnancy-associated plasma protein-A (PAPP-A) was detected by RIA in human seminal plasma. This was not due to interference with proteases or binding to seminal plasma proteins, since immunoreactivity was not affected by treatment with protease inhibitors, and the elution of [125I]PAPP-A was not altered by preincubation with seminal plasma. The major component of the seminal plasma PAPP-A coeluted with pure PAPP-A or plasma PAPP-A from pregnant and nonpregnant women. In the RIA, serial dilutions of seminal plasma gave parallel displacement curves to pregnancy plasma. Removing PAPP-A-like material from seminal plasma by adsorbtion to heparin-Sepharose reduced the inhibitory effect of seminal plasma on phytohemagglutinin-induced lymphocyte transformation. The source of seminal plasma PAPP-A-like immunoreactive material remains to be elucidated, but it is unlikely to be the testis, since PAPP-A levels in semen of vasectomized men were similar to those in nonvasectomized men.

Female↗
PubMed1981

Cartilage response to plasma and plasma somatomedin activity in rats related to growth before and after birth.

Cartilage response to plasma, plasma somatomedin activity, body weight and length were measured in rats from 15 days of fetal age to 37 days postnatally. The metabolic activity of costal cartilage was assessed by the incorporation of [35S]sulphate in basal medium and after stimulation by plasma. It was found that (a) A significant stimulation of isotope uptake above basal levels occurred in the presence of 15% standard adult rat plasma at every age studied. (b) The degree of stimulation, a measure of cartilage sensitivity to plasma growth factors, increased through the latter part of fetal life but fell after birth. A high degree of cartilage stimulation was seen on day 6 of postnatal life. (c) The changes in cartilage sensitivity and in the stimulated isotope uptake, resembled the changes observed in growth rate for body weight, nose-rump length and tail length. (d) Plasma somatomedin activity measured by the pig costal cartilage assay was low in the fetus and neonate but rose to adult values 9 days after birth. However, plasma from fetal or neonatal rats tested on cartilage from rats of the same age was equipotent to adult rat plasma. (e) Plasma from hypophysectomized adult rats had a low potency in stimulating isotope uptake by neonatal rat cartilage but was equipotent to normal adult rat plasma in its action on fetal cartilage. (f) The action of plasma from hypophysectomized rats on fetal cartilage was unaffected by dialysis but was destroyed by incubation with trypsin.

Animals↗
PubMed2005

International movement of plasma and plasma contracting.

Plasma fractionation is a global business characterised by technological stability, increasing consolidation and a high level of regulatory oversight. All these factors affect the ease with which plasma derivatives can be accessed in the world market. As domestic regulatory measures in the first world blood economies become increasingly resonant to the precautionary approach, the availability of plasma as a raw material, as well as its cost, become an increasingly significant component in the cost of the final product. This decreases the amount of plasma which fractionators are able to allocate for export activities. Also, regulatory standards in the country of manufacture will reflect priorities in that country which may not be similar to those in export markets, but which will affect entry to those markets. While many countries possess a fractionation capacity, the limiting factor in supply worldwide is the amount of plasma available, and nationalistic drivers for each country to have its own plant are inimical to product safety and supply. Rather, the provision of sufficient supplies of domestic plasma should be the focus of resource allocation, with a choice of an appropriate contract fractionator. However, contract fractionation too may be affected by domestic considerations unrelated to the needs of the country of plasma origin. This chapter will review the global plasma market and the influences on plasma and plasma product movement across national borders. Problems in ensuring adequate safety and supply will be identified, and some tentative approaches to the amelioration of current barriers to the provision of plasma derivatives will be outlined.

Blood Transfusion↗
PubMed1996

Hyaluronan-dependent motility of B cells and leukemic plasma cells in blood, but not of bone marrow plasma cells, in multiple myeloma: alternate use of receptor for hyaluronan-mediated motility (RHAMM) and CD44.

We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with multiple myeloma (MM) to migrate on extracellular matrix proteins. Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin, promoted migration of MM blood B cells, as determined by time-lapse video microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an average velocity of 19 micron/min, and greater than 75% of MM blood B cells exhibited vigorous cell movement and plasma membrane deformation, as did circulating T-PCL and extraskeletal plasma cells from patients with MM. In contrast, plasma cells obtained from BM of patients with MM lacked motility on all substrates tested and did not exhibit cell membrane protrusions or cellular deformation. MM blood B cells and MM plasma cells from all sources examined expressed the HA-binding receptors receptor for HA-mediated motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44 participated in HA-binding, indicating their expression ex vivo in an activated conformation. In contrast, for the majority of BM plasma cells in the majority of patients with MM, expression of RHAMM or CD44 was not accompanied by HA binding. A minority of patients did have HA-binding BM plasma cells, involving both RHAMM and CD44, as evidenced by partial blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA binding by both RHAMM and CD44, migration of MM blood B cells on HA was inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM but not CD44 mediates motility on HA. Thus, circulating B and plasma cells in MM exhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a subset(s) of circulating B or plasma cells mediates malignant spread in myeloma.

B-Lymphocyte Subsets↗