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Biomedical subjects

T A Lane

Publications and source records attributed to T A Lane.

At least 19 recordsLinked to original sources
PubMed1992

Leukocyte reduction in blood component therapy.

PURPOSE: To review methods of preventing or minimizing the adverse effects associated with the transfusion of passenger leukocytes present in cellular blood components and to define groups of patients who are at risk for adverse effects. DATA SOURCES: English-language articles on transfusion medicine. STUDY SELECTION: Original reports describing the pathogenesis of leukocyte-induced adverse effects in transfusion recipients and the influence of leukocyte-reduced blood components on these effects. DATA EXTRACTION: Evaluation of the diagnosis, transfusion history, and treatment of the study patients; the methods and results of leukocyte reduction; and specific outcomes, including development of alloimmunization to leukocytes, febrile reactions to transfusion, and platelet refractoriness. DATA SYNTHESIS: Passenger leukocytes are the chief cause of alloimmunization to human leukocyte antigen (HLA) and leukocyte-specific antigens in transfusion recipients. Alloimmunization may result in febrile transfusion reactions, platelet refractoriness, and acute lung injury. Leukocytes are also the vector for transfusion-associated cytomegalovirus infection. Technologic advances in the leukocyte reduction of cellular blood components have made it possible to reduce the number of leukocytes to fewer than 10(7) per transfusion. Findings suggest that the use of leukocyte-reduced cellular blood components may minimize or prevent recurrent febrile reactions and alloimmunization to leukocyte antigens. Cytomegalovirus may not be transmitted by blood components containing fewer than 10(7) leukocytes. CONCLUSIONS: Leukocyte reduction in red blood cell and platelet transfusions using third-generation filters is indicated for selected patients who are likely to receive long-term transfusion support, to prevent recurrent febrile reactions and to prevent or delay alloimmunization to leukocyte antigens. Leukocyte-depleted transfusions may also be indicated to delay or prevent refractoriness to platelet transfusion.

Blood Component Transfusion↗
PubMed1992

Reducing the risk for transfusion-transmitted cytomegalovirus infection.

OBJECTIVE: To define the groups of patients at risk for transfusion-transmitted cytomegalovirus infection and to define the methods to reduce this risk. DATA SOURCES: English-language publications on transfusion medicine. STUDY SELECTION AND DATA EXTRACTION: Studies were selected that described cytomegalovirus infection in transfusion-dependent patients. Special attention was paid to reports that included observations about the prevalence and clinical manifestations of cytomegalovirus infection and recommendations for the prevention of infection. DATA SYNTHESIS: Some patients with impaired immune responses who have never been exposed to cytomegalovirus are at risk for transfusion-transmitted cytomegalovirus infection. This infection, which is associated with substantial morbidity and mortality, can be avoided by additional screening of blood donors or by special processing of components for transfusion. CONCLUSIONS: Transfusion products that are unlikely to transmit cytomegalovirus infection can be prepared by filtration to remove leukocytes or can be obtained by selecting donors who are seronegative for antibodies to cytomegalovirus. These products are indicated for certain groups of immunosuppressed patients, including pregnant women who are cytomegalovirus seronegative, premature infants of low birth weight who are born to cytomegalovirus-seronegative mothers, cytomegalovirus-seronegative recipients of allogeneic bone marrow transplants from cytomegalovirus-seronegative donors, and cytomegalovirus-seronegative patients with the acquired immunodeficiency syndrome (AIDS).

Cytomegalovirus Infections↗
PubMed1992

Biological actions of monoclonal luteinizing hormone/human chorionic gonadotropin receptor antibodies.

Several recent studies have elucidated the structure of the mammalian LH/hCG receptor; as reported in the present work, we have developed a series of monoclonal antibodies (mAbs) against the rat ovarian LH/hCG receptor using highly purified receptor as immunogen and by screening hybridomas with purified LH/hCG receptors. The mAbs were able to specifically immunoprecipitate LH/hCG receptors from solubilized preparations of rat ovarian membranes as well as from partially purified preparations. Western blotting with mAb P1B4 detected a probable receptor dimer and a receptor fragment in rat and porcine ovarian tissue but not in other tissues. This mAb also partially inhibited hCG binding to rat and porcine ovarian tissues. The receptor mAbs were able to inhibit hCG-induced progesterone synthesis in cultured human and porcine granulosa cells without affecting cAMP- and FSH-induced progesterone synthesis. The mAb P1B4 was used to demonstrate that the majority of ovarian receptors are internalized after hCG treatment and that in pseudopregnant rats receptors are present in the rough endoplasmic reticulum and in microvesicles. Bovine corpus luteal cells also contained P1B4 binding sites, as detected by immunohistochemical technique. Taken together, these results suggest that the mAbs are specific for the LH/hCG receptor, mAb P1B4 recognizes an epitope that is highly conserved among mammals, and this epitope is probably in the extracellular domain.

Animals↗
PubMed1992

The effect of peritoneal macrophage-derived factor(s) on ovarian progesterone secretion and LH receptors: the role of calcium.

Macrophages and their secretory products, cytokines, play an integral role in many reproductive processes. In this study we examined the effect of conditioned media from cultured human peritoneal macrophages on progesterone production by granulosa cells and the role of calcium in this process. Macrophages were pretreated with various concentrations of a calcium channel blocker (verapamil) or a calcium ionophore (A23187). Macrophage-conditioned media (MCM) or cell-free media that contained calcium channel modifiers were added at three dose levels to cultured porcine granulosa cells. Progesterone production and LH receptor content were determined. Macrophage-conditioned media alone elevated basal progesterone production, but significantly attenuated granulosa cell LH receptor content. These effects were neither potentiated nor suppressed by pretreating macrophages with verapamil. However, production of the LH receptor lowering factor(s) appeared to be suppressed by calcium ionophore. We conclude that (1) one or more factors produced by macrophages have a net stimulatory effect on basal progesterone production and these factor(s) may not be calcium-dependent and (2) macrophage-derived secretory products reduce granulosa cell LH receptor content. The production of these factor(s) may be calcium-dependent.

Animals↗
PubMed1992

Hypoxia induces endothelial cells to increase their adherence for neutrophils: role of PAF.

We investigated the interactions of polymorphonuclear neutrophils (PMN) and endothelial cells in myocardial ischemia using a hypoxia model. We exposed porcine aortic (PAEC) and porcine coronary microvessel (PCMEC) endothelial cells to 2% O2 for 2 h (PO2 = 53 mmHg) and measured the adherence of unstimulated neutrophils (PMN) to both control and hypoxia-conditioned endothelial cell monolayers. Hypoxia conditioning increased PMN adherence to PAEC and PCMEC by 51 and 101%, respectively, above control levels. The increase in PMN adhesion to PAEC was associated with a threefold increase in endothelial cell-associated platelet-activating factor (PAF) compared with control PAEC. The conditioned media from PAEC exposed to hypoxia also contained sixfold more PAF than control conditioned media, and it activated PMN to become adherent to untreated PAEC. The hypoxia-induced PAEC adhesion response was inhibited by preincubating PMN with the specific PAF receptor antagonist, L-659,989. We conclude that PAF is produced by cultured endothelial cells in response to hypoxia and that PAF generation is chiefly responsible for the increased adherence properties of hypoxia-conditioned endothelial cells. This response may play a major role in regulating PMN margination during myocardial ischemia.

Animals↗
PubMed1992

Effect of a high concentration perfluorocarbon emulsion on platelet function.

Perfluorocarbon (PFC) and lipid emulsions (eg. Fluosol, Intralipid,) containing phospholipid have been reported to modify platelet function after intravenous infusion. Platelet activation might be responsible for the generation of mediators responsible for PFC-induced side effects. In view of this, we investigated the effect of a highly concentrated perfluorocarbon emulsion containing 90% (w/v) perfluorooctylbromide (perflubron; PFOB), on porcine and human platelet activation and function. We measured both: a) stimulated ex-vivo porcine platelet aggregation pre and post infusion of either perflubron or control (vehicle only) emulsions, and b) stimulated in vitro human platelet calcium flux in the presence of perflubron emulsion or control emulsions. Platelet aggregation stimulated by collagen, ADP or arachidonic acid (AA) was inhibited in ex-vivo porcine platelets following infusion of perflubron emulsion at a dose of 3 ml/kg (0.2 ml/kg/min). Inhibition was dose dependent and was decreased when the dose of perflubron emulsion was reduced to 1.0 or 0.3 ml/kg. Infusion of saline or "vehicle" emulsions had little or no effect on stimulated ex-vivo pig platelet aggregation. Fluosol, infusion was associated with inconsistent inhibition of platelet aggregation. A23187- or AA-stimulated calcium flux of human platelets in vitro was inhibited in the presence of 1% (v/v) perflubron emulsion. Similar effects were seen with Fluosol, or Intralipid. This inhibition was agonist dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Heterologous down-modulation of luteinizing hormone receptors by prolactin: a flow cytometry study.

Although the binding, internalization, and regulation of LH, PRL, and their respective receptors have been extensively studied, it is not known whether the receptors are coordinately regulated. Using double labeling experiments, we have previously shown that receptor-bound LH and PRL can be colocalized in identical endosomes of granulosa cells. We hypothesize that high levels of PRL may induce a heterologous down-modulation of LH receptors, consequently reducing ovarian responsiveness to further gonadotropin stimulation. In this study we used a novel procedure to enrich endosomes containing internalized PRL and to determine whether unoccupied LH receptors were cointernalized in granulosa cells. Porcine granulosa cells were obtained from medium-sized (3-5 mm) follicles and cultured for 4 days in the presence of FSH. Fluorescein isothiocyanate-labeled PRL (FITC-PRL) was used as a ligand to induce internalization of PRL receptors and as a marker to label endosomes. Granulosa cells were incubated with FITC-PRL at either 4 or 37 C for various times. At the end of the incubation, cells were trypsinized to remove surface receptors and then homogenized. The postnuclear fraction containing endosomes and other subcellular organelles was sorted using a FACStar Plus cell sorter. Results from 14 separate sorting experiments showed that 1) FITC-PRL-treated cells exhibited a sorting pattern distinct from that of FITC-BSA-treated or untreated cells; 2) excess unlabeled PRL partially shifted the sorting profile to one similar to that in controls; 3) the differences in sorting profiles were not due to free FITC; and 4) using this method, it was possible to isolate FITC-PRL-containing endosomes that were virtually devoid of other contaminating subcellular particles. Fluorescently positive (FITC-PRL-containing) organelles were collected and assayed for LH receptors using [125I]hCG as a tracer. When the cells were incubated with FITC-PRL at 37 C for 3 h, the number of available LH receptors (as determined by [125I]hCG binding) was 37% higher in particles containing FITC-PRL than in those devoid of FITC-PRL. If the cells were allowed to preincubate with FITC-PRL at 4 C for 10-16 h before raising the temperature to 37 C, the number of available LH receptors in FITC-PRL-containing endosomes was about 7-fold higher than that in FITC-negative endosomes. Results from this study suggest that PRL not only induces internalization of its own receptor, but also causes down-modulation of unoccupied LH receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Protein kinase C inhibitors block the enhanced expression of intercellular adhesion molecule-1 on endothelial cells activated by interleukin-1, lipopolysaccharide and tumor necrosis factor.

Interleukin 1 (IL-1), bacterial lipopolysaccharide (LPS) and tumor necrosis factor (TNF alpha) enhance the adherence properties of endothelial cells (EC) for neutrophils (PMN). This is mediated in part by the up-regulation of Intercellular Adhesion Molecule 1 (ICAM-1) on EC. Phorbol esters, which activate protein kinase c (PKC) and enhance the adherence properties of EC for PMN also up-regulate the ICAM-1 expression on EC. We investigated the effect of PKC inhibitors on ICAM-1 expression of human umbilical vein EC (HUVEC). Staurosporine (STS) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) prevented inflammatory mediator-dependent stimulation of both ICAM-1 expression and PMN adherence by HUVEC (ID50 for STS = 2.7-2.9 microM; for H-7 = 7.6-8.8 microM). Inhibition was dose and time-dependent and was not due to HUVEC toxicity. The STS analog K252a and the H-7 analog W-7 were less potent inhibitors of ICAM-1 up-regulation and adherence promotion. Prolonged exposure of HUVEC to phorbol myristate acetate down-regulated PKC activity and inhibited subsequent ICAM-1 up-regulation by this agent and by IL-1. We conclude that inflammatory mediator induced stimulation of HUVEC expression of ICAM-1 and promotion of adherence properties are mediated in part by activation of PKC.

Cell Adhesion↗
PubMed1990

Granulocyte storage.

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Blood Component Transfusion↗
PubMed1990

Effects of cytokines on porcine granulosa cell steroidogenesis in vitro.

Recent evidence indicates that factors produced by immune cells (cytokines) may play a role in ovarian function. To explore this possibility, we examined the effects of conditioned medium obtained from cultures of either unstimulated splenocytes (splenocyte-conditioned medium; SCM) or concanavalin A-stimulated splenocytes (CAS) on estrogen and progesterone production by porcine granulosa cells. Granulosa cells were obtained from small (less than 3 mm) or large (greater than 7 mm) follicles and treated with increasing doses of SCM or CAS in the presence or absence of pFSH (100 ng/ml) for 24 h at 37 degrees C. In granulosa cells obtained from small follicles it was found that both SCM and CAS evoked a dose-dependent increase in estrogen but not progesterone production. Estrogen production was no further enhanced by the presence of FSH. Additionally, SCM was able to augment FSH-stimulated progesterone production by these cells, whereas CAS had no effect. Identical treatment of granulosa cells obtained from large follicles demonstrated that both SCM and CAS caused dose-dependent increases in estrogen as well as progesterone production. In response to CAS, FSH augmented progesterone production but exerted a biphasic on estrogen production (inhibiting at lower doses while stimulating at higher doses). In contrast, SCM had no effect on FSH-stimulated estrogen production. Additional controls indicated that the above results could not be attributed to either concanavalin A or serum. Taken together, these findings suggest that cytokines can exert significant effects over granulosa cell steroidogenesis and further imply that these factors may play an important role in the differentiation and developmental regulation of granulosa cell function.

Animals↗
PubMed1989

Modulation of endothelial cell expression of intercellular adhesion molecule 1 by protein kinase C activation.

Inflammatory stimuli enhance the adherence properties of human umbilical vein endothelial cells (HUVEC) for neutrophils (PMN). This is mediated in part by the up-regulation on HUVEC of Intercellular Adhesion Molecule 1 (ICAM 1). Phorbol esters, which activate protein kinase c (PKC), have also been reported to enhance the adherence properties of HUVEC for PMN. We investigated the effect of agents which activate PKC on the expression of ICAM 1 by HUVEC. Both phorbol myristate acetate (PMA) and Mezerein, a non-phorbol which also stimulates PKC, enhanced both the expression of ICAM 1 on HUVEC and the adherence of HUVEC for PMN. The PKC inhibitors staurosporine and H-7 prevented both PMA and Mezerein-induced stimulation of HUVEC expression of ICAM 1 and adherence for PMN. We conclude that activation of PKC in HUVEC is associated with increased expression of ICAM 1 on HUVEC. PKC-mediated up-regulation of ICAM 1 may be responsible, in part, for the promotion of endothelial cell adherence properties toward PMN.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Apparent coagulopathy caused by infusion of shed mediastinal blood and its prevention by washing of the infusate.

We found that reinfusion of shed mediastinal blood (SMB) after a cardiac operation was associated with laboratory evidence of disseminated intravascular coagulation. In view of this, we compared the effect of infusing washed or unwashed SMB on the coagulation profiles and blood use of two serial groups of patients undergoing cardiopulmonary bypass. We found that the results of testing for fibrin degradation products converted from negative to positive in 17 of 20 patients who received unwashed SMB versus 1 of 14 patients who received washed SMB (p less than 0.0001). Other coagulation studies did not reveal disseminated intravascular coagulation in either group, nor were there differences in blood use between the two groups. The unwashed SMB contained high titers of fibrin degradation products (mean reciprocal titer = 354 +/- 161) compared with washed SMB (mean reciprocal titer = 34 +/- 18) (p less than 0.01). Based on the volume of SMB infused, the amount of fibrin degradation products in unwashed SMB was sufficient to account for the positive fibrin degradation product assays after infusion in this group. We conclude that infusion of unwashed SMB may confuse the interpretation of tests for disseminated intravascular coagulation or fibrinolysis. As this could lead to unnecessary blood component use and is preventable by washing before infusion, we recommend that the routine infusion of unwashed SMB no longer be employed.

Blood Coagulation Tests↗
PubMed1989

The effect of storage on the metastatic potential of tumor cells collected in autologous blood. An animal model.

Malignancy in a potential autologous blood donor is considered by some as a relative contraindication for the collection of autologous blood. There is, however little experimental information regarding the safety of transfusion of autologous blood that may contain viable tumor cells. The purpose of this study was to determine if tumor cells seeded into autologous blood retain their metastatic potential and, if so, for how long. A well-established model of the pulmonary metastasis of B16/F10 (F10) melanoma in C57BL/6 mice was used. Equal numbers of F10 cells were seeded into CPDA-1 blood from the mice or into saline, and the number of lung tumors was evaluated 14 days after infusion of blood or saline. The CPDA-1 blood seeded with F10 cells was stored for up to 21 days in transfer packs at 4 to 6 degrees C, and the metastatic potential of F10 cells in the stored blood was ascertained as above. F10 cells seeded into autologous blood that was then transfused without storage gave rise to the same number of metastatic foci (404 +/- 32 metastases) as did those cells transfused in saline (374 +/- 38, p = 0.5). In contrast, the number of metastatic foci resulting from the transfusion of blood containing F10 cells decreased progressively after storage of the blood (7 days = 124 +/- 14 metastases; 14 days = 7 +/- 1; 21 days = 2 +/- 1; all p values less than 0.001 vs fresh blood). Also, the predilection of F10 cells to metastasize to the lung was unchanged by storage in blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects on flow, granulocytes, and injury.

Morbidity and mortality from acute coronary artery occlusion may be reduced if local myocardial adenosine concentration is augmented because 1) coronary collateral blood flow during ischemia increases with adenosine infusion, and 2) granulocytes that accumulate in the microcirculation during ischemia are, to a large extent, inhibited by adenosine from generating superoxide anion free radicals, from adhering to vascular endothelium, and from damaging endothelial cells in culture. Using a cultured lymphoblast model system, we found that 5-amino-4-imidazole carboxamide (AICA) riboside enhanced adenosine accumulation during ATP catabolism. Therefore, AICA riboside pretreatment was used in canine myocardium to selectively increase adenosine concentration in the ischemic area during 1 hour of ischemia. At 5 minutes of ischemia, endocardial flow to ischemic myocardium in saline-treated and AICA riboside-treated dogs was 0.06 +/- 0.03 and 0.34 +/- 0.11 ml/min/g, respectively (p less than 0.01); flow to nonischemic myocardium was not affected. Ventricular tachycardia and premature ventricular depolarizations were significantly attenuated in the AICA riboside-treated dogs. Blood pressure and heart rate were not affected by AICA riboside. In venous blood from ischemic tissue, adenosine increased from undetectable levels (less than 0.01 microM) to 0.22 +/- 0.08 microM in saline and 1.79 +/- 0.06 microM in AICA riboside-treated dogs, respectively (p less than 0.001). Coronary vein inosine concentrations were greater in saline than in AICA riboside-treated dogs. In separate in vitro studies, AICA riboside did not alter the removal rate of adenosine from canine blood. Indium-labeled granulocyte accumulation was significantly less in ischemic myocardium in AICA riboside-treated compared with saline-treated dogs. In addition, adenosine, but not AICA riboside, inhibited in vitro canine granulocyte superoxide production. We conclude that AICA riboside given before myocardial ischemia augments adenosine concentration, decreases arrhythmias, decreases granulocyte accumulation, and improves collateral flow to ischemic myocardium. One of the beneficial mechanisms could be an increased production of adenosine rather than inosine from ATP catabolism that causes vasodilation and inhibition of granulocytes. We propose a new hypothesis regarding regulation of the inflammatory reaction to ischemia in the microcirculation. Adenosine, in addition to its vasodilator action, is an anti-injury autacoid that links ATP catabolism to inhibition of granulocyte adherence, microvascular obstruction, and superoxide anion formation.

Adenosine↗
PubMed1986

Increased infection mortality and decreased neutrophil migration due to a component of an artificial blood substitute.

We previously showed that an artificial blood substitute containing perfluorocarbons, Fluosol-DA, inhibited both neutrophil migration and adherence, due to its detergent component, Pluronic F-68. The purpose of the studies we report here was to determine if Fluosol or Pluronic might also reduce in vivo neutrophil migration and impair host resistance to bacterial infection. We studied in vivo PMN migration by injecting mice intraperitoneally (IP) with glycogen, followed by intravenous (IV) infusion of saline, Fluosol, or Pluronic. Peritoneal lavage after eight hours showed a significant decrease in the accumulation of PMN in lavage fluids of animals given either Fluosol or Pluronic (control--.19 +/- .03 X 10(6) PMN/mL, glycogen--1.35 +/- .14; glycogen/Fluosol--0.63 +/- .12; glycogen/Pluronic--0.69 +/- .07). We ascertained the effect of Fluosol and Pluronic on infection mortality by injecting mice IV with saline, Fluosol, or Pluronic, followed by a quantity of E coli (0.6 X 10(7] IP shown in preliminary studies to kill 20% to 50% of the mice in 24 hours. The 24-hour mortality was 14/45-saline, 24/32-Fluosol (chi 2 = 17.1; P less than .001) and 17/23 - Pluronic (chi = 11.2; P less than .001). Neither Fluosol nor Pluronic caused mortality without E coli. The increase in infection mortality occurred when Fluosol was given either two hours before, or simultaneously with E coli, but only with the simultaneous administration of bacteria and Pluronic. Pluronic did not alter reticuloendothelial system (RES) clearance function. These studies indicate that, in an animal model, Fluosol-DA, due to its detergent component Pluronic F-68, impaired neutrophil delivery to an inflammatory locus, and resulted in an increased rate of infection mortality. Since Pluronic did not result in RES blockade, but did impair the delivery of PMN to an inflammatory locus, our results suggest that the latter effect is responsible for the increase in infection mortality.

Animals↗
PubMed1979

Granulocyte concentrate function during preservation: effect of temperature.

Granulocyte concentrates collected from normal donors are necessarily stored for varying intervals up to the time of transfusion. However, information regarding the fate of collected cells and the optimal mode of storage in vitro in the interval between collection and transfusion is far from complete. We studied granulocyte function during preservation of granulocyte concentrates for up to 72 hr. The initial and most consistent alteration in granulocyte function during storage was failure of random migration and chemotaxis after 24 hr of storage (50% and 61% of normal, respectively). By 48 hr the respiratory burst was decreased by 42%, whereas at 48 hr phagocytic and bactericidal activities were nearly normal. Defects in migration and respiratory burst are not due to delayed activation of these functions but to absolute decreases in maximum rates of migration and oxygen consumption. Comparison of granulocyte concentrate storage at 6 degrees C versus room temperature indicated at 24 hr an improved (p greater than 0.02) but still abnormal (p greater than 0.02) chemotactic response with 24 degrees C storage and at 48 hr no difference in migration but a slight advantage in bacterial killing at 6 degrees C storage. These studies show that severe impairment of granulocyte function occurs within 24 hr of collection by centrifugal means; consequently, granulocyte concentrates should be transfused as soon as possible after collection.

Blood Bactericidal Activity↗