Anaphylactic shock after retreatment with OKT3 monoclonal antibody.
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Adolescent↗
Biomedical subjects
M Goldman
Publications and source records attributed to M Goldman.
[Colony stimulating factors as a treatment modality for acute radiation syndrome].
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Acute Disease↗
Induction of thromboses within renal grafts by high-dose prophylactic OKT3.
Among 93 consecutive kidney-transplant patients who received prophylactic OKT3 10 mg/day for 2 weeks, 9 had intragraft thromboses within 2 weeks of transplantation. The thromboses were in graft artery in 1 patient and veins in 3. The other 5 had thromboses in glomerular capillaries and thrombotic microangiopathy similar to that of haemolytic-uraemic syndrome. All attempted treatments failed, and the 9 grafts had to be removed. The finding that plasma concentrations of prothrombin fragment 1 and 2 were higher 4 h after the first OKT3 dose in OKT3 recipients than in transplant patients who received other prophylaxis (mean 5.88 [SEM 0.76] vs 2.25 [0.59] nmol/l, p less than 0.01) confirms that OKT3 has procoagulant effects in vivo.
Humans↗
An animal model of allogeneic donor platelet refractoriness: the effect of the time of leukodepletion.
Approximately 50% of multi-transfused individuals become refractory to random donor platelets. Recent clinical data suggest that those patients receiving leukocyte-depleted blood products are less likely to become refractory to random donor platelets than recipients of non-leukocyte-depleted products. Leukocyte depletion can be performed immediately after collection of a unit of whole blood before its storage (prestorage leukodepletion) or just before the transfusion of the blood product to a recipient, after its storage (poststorage leukodepletion). However, the most appropriate time for the leukodepletion of blood products has not been established. The present study was undertaken to establish an animal model of allogeneic platelet refractoriness, and to compare the effect of prestorage and poststorage leukodepletion on the frequency of refractoriness to allogeneic donor platelets. In this model, two strains of rabbits were used: California Black rabbits were used as blood donors, while New Zealand White rabbits were used as recipients. Eight weekly infusions of nonleukodepleted allogeneic fresh blood resulted in an allogeneic platelet refractory rate of 91.2% (31/34). The prestorage leukodepletion of the donor blood was associated with a significantly higher allogeneic platelet survival and lower refractory rate (33.3%) to allogeneic platelets than poststorage leukodepletion (66.7%). Furthermore, the data suggest that cell-free plasma products are capable of inducing refractoriness to allogeneic donor platelets; the stored plasma having a greater likelihood of inducing such refractoriness than fresh plasma. Thus, these data provide evidence that the prestorage leukodepletion of allogeneic donor blood is associated with a lower frequency of refractoriness and better allogeneic platelet survival than poststorage leukodepletion.
Animals↗
The injection of deaggregated gamma globulins in adult mice induces antigen-specific unresponsiveness of T helper type 1 but not type 2 lymphocytes.
Injection of adult mice with high doses of monomeric human gamma globulins (dHGG) has been previously shown to produce a state of peripheral tolerance in both B and T cells. To gain insight into the mechanism of induction and maintenance of adult tolerance in this model, we have analyzed the pattern of lymphokines produced by control and tolerant animals in response to the tolerogen. The data presented indicate that HGG-specific, interleukin 2 (IL-2)- and interferon gamma (IFN-gamma)-producing T cells (thus referred to as T helper type 1 [Th1] cells) are rendered unresponsive after in vivo administration of soluble HGG. In contrast, antigenic stimulation of T cells isolated from tolerant adult mice leads to increased production of IL-4 in vitro. In vivo challenge of dHGG-treated adult animals with hapten-coupled HGG (p-azophenylarsonate [ARS]-HGG) induced a significant ARS-specific antibody response, suggesting that tolerance induction in this model does not completely abrogate tolerogen-specific Th activity in vivo. In agreement with the in vitro data, hapten-specific antibody response of tolerant animals is characterized by a selective deficiency in the IFN-gamma-dependent IgG2a subclass. Injection of immunogenic forms of HGG into tolerant animals also produced an IL-4-dependent increase in total serum IgE levels, indicative of an increased activity of HGG-specific Th2 cells in these animals. The finding that tolerance induction differentially affects Th subpopulations suggests that crossregulation among lymphocyte subsets may play a role in the induction and/or maintenance of acquired tolerance in adults.
Animals↗
Lipopolysaccharide induces up-regulation of CD14 molecule on monocytes in human whole blood.
We examined by flow cytometry the expression of lipopolysaccharide (LPS) receptor CD14 molecule on monocytes after addition of LPS to human whole blood. Within 30 min LPS induced an increase in monocyte CD14 expression, peaking between 1 and 3 h and followed by a slow decrease. Maximal increase in anti-CD14 monoclonal antibody binding sites was estimated as twofold the basal value. This effect, already observed with very low concentrations of LPS (10 pg/ml), was dose dependent. Protein synthesis was not involved in the CD14 hyperexpression since it was not influenced by co-incubation with cycloheximide. Finally, LPS-induced up-regulation of monocyte CD14 was associated with an increased binding of fluoresceinated LPS. We conclude that LPS in whole blood up-regulates the expression of its own CD14 receptor on monocytes, a phenomenon that could be relevant to the pathogenesis of gram-negative sepsis.
Antigens, CD↗
Kinetics of action of salbutamol inhaled from a metered dose inhaler (MDI) and a "Diskhaler".
In a double-blind cross-over study, 12 patients with reversible airways obstruction were treated with 200 micrograms salbutamol base in aerosol or 400 micrograms of powder following methacholine-induced bronchoconstriction. Salbutamol was inhaled either from a conventional metered dose inhaler (MDI) or from an inhaler (Diskhaler) utilizing the powdered form of the drug. The efficacy of both forms was identical whether assessed in terms of FEV1 or vital capacity. The ratio of the increase in FEV1 or vital capacity after bronchodilatation to the decrease during the prior bronchoconstriction was 1.4, indicating that both FEV1 and vital capacity improved over baseline following bronchodilatation. In six subjects, the onset of action of the powder form was more rapid, and in four the MDI acted more rapidly. In the group as a whole, the mean time constant for the action of salbutamol was identical (3.8 min) for the two forms. It is concluded that salbutamol powder has a similar efficacy and time course of action as the aerosol, probably because both formulations produce similar sized particles of the drug.
Administration, Inhalation↗
Effect of dietary fiber on colonic bacterial enzymes and bile acids in relation to colon cancer.
Because of the potential significance of colonic bacteria and secondary bile acids in the pathogenesis of colon cancer, the present study investigated the effect of different types of dietary fiber on fecal bacterial enzymes, namely, beta-glucuronidase, 7 alpha-dehydroxylase, nitroreductase, and azoreductase, and on bile acids and neutral sterols in premenopausal women. The subjects consumed 13-15 g of wheat, oat, or corn bran daily for 8 weeks in addition to their normal diet. Stools collected during the normal and fiber diet periods were analyzed for the above constituents. Dietary wheat bran decreased the concentrations of fecal deoxycholic acid, lithocholic acid, 12-ketolithocholic acid, and neutral sterols and the activities of all bacterial enzymes. Oat bran had no effect on secondary bile acids and 7 alpha-dehydroxylase but decreased beta-glucuronidase, nitroreductase, and azoreductase levels. Dietary corn bran increased 7 alpha-dehydroxylase, lithocholic acid, and cholesterol levels and decreased deoxycholic acid coprostanol, cholestenone, nitroreductase, and azoreductase levels. These results show that the modifying effect of dietary fiber on secondary bile acids and bacterial enzymes that may play a role in carcinogenesis depends on the type of fiber consumed.
Adult↗
Comparative tissue tolerance of a new endodontic sealer.
An experimental radiopaque resin root canal sealer was tested for tissue biocompatibility in rat connective tissue. The controls were four widely used sealers: Sealapex, Kerr's sealer, AH-26, and Roth's sealer. Polyethylene tubes were filled with the sealers and allowed to set for 24 hours in 100% humidity. Each sealer was implanted in the connective tissue of Sprague-Dawley rats and removed after 3, 10, 20, 30, and 60 days, fixed, and histologically prepared for light microscope evaluation. At each time period there was practically no difference in the reaction of all the sealers. By 60 days, the total picture was one of well-tolerated biocompatibility.
Animals↗
Control of ventilation in androgenized hypogonadal male rats.
We have previously shown that subcutaneous administration of aspartic acid (a dicarboxylic acidic amino acid) at a dose of 580 mg/kg causes long lasting depression of ventilation in adult intact and postpubertally castrated male rats, but not in intact female rats. The purpose of the present study was to determine if hypogonadism induced by perinatal administration of testosterone propionate (TP) will alter ventilation, oxygen consumption, and the ventilatory response to aspartic acid and to hypercapnia in adult males. TP treatment resulted in adult males who had lower body, prostate, heart, and testes weights than those of control male rats. Ventilation in air and oxygen consumption were comparable between the two groups as was the ventilatory response to aspartic acid. In contrast, TP-treated rats exhibited a significantly decreased ventilatory response to hypercapnia due predominantly to lower tidal volumes compared to control animals. Aspartic acid treatment did not affect oxygen consumption in either group. Thus, TP treatment results in the development of adult male rats who, although hypogonadal, retain a male-like ventilatory response to aspartic acid, but whose response to hypercapnia is more like that of hypogonadal men and rats.
Animals↗
Perinatal estradiol benzoate administration affects control of ventilation in adult male rats.
One injection of estradiol benzoate (EB) (100 micrograms) or vehicle was administered to male rat pups 5 days after birth. Two months later ventilation, ventilatory responses to 7% carbon dioxide, and to 580 mg/kg aspartic acid (an agent used as a marker of sexually dimorphism in the control of ventilation) were evaluated and body weight, testes weight, and nose-anus length were measured in animals in each group. The EB-treated rats had similar tidal volumes, frequency of breathing, and minute ventilation as did control male rats. The ventilatory responses of EB-treated rats to hypercapnia were markedly less than those of control animals. Aspartic acid administration depressed ventilation in control animals, but had no effect on ventilation in EB-treated males. Body and testes weights, as well as nose-anus length, were less in EB-treated compared with control rats. However, when body weight was normalized by nose-anus length and testes weight was normalized by body weight, the values were comparable between the two groups. Thus, perinatal EB treatment of male rat pups results in small, hypogonadal adult animals whose ventilation in response to hypercapnia was diminished and whose response to aspartic acid was female-like relative to those of control rats.
Animals↗
Upregulation of adhesion molecules induced by broncho-vaxom on phagocytic cells.
Whole blood was incubated with the bacterial extract Broncho-Vaxom (OM85) at various concentrations and for different periods of time. Expression of the beta 2-integrins (LFA-1, CD11a/CD18; MAC-1, CD11b/CD18; p150,95, CD11c/CD18) and ICAM-1 (CD54) by monocytes and granulocytes was studied using flow cytometry. OM85 enhanced the expression of MAC-1 and ICAM-1 on monocytes and granulocytes in a dose-dependent manner. Maximal expression was achieved with 1 mg/ml bacterial extract. The effect on MAC-1 expression was not due to the low concentration of endotoxin contaminating the preparation (less than 1 ng/mg) since polymyxin-B did not substantially affect the adhesion molecule upregulation induced by OM85. In addition, OM85 enhanced the expression of p150,95 on monocytes and granulocytes, and also increased expression of LFA-1 on monocytes, but not on granulocytes. While MAC-1 and p150,95 expression reached peak values between 1 and 6 h, levels of ICAM-1 rose constantly for 10 h. We suggest that the clinical interest of OM85 in the management of recurrent infections could be related to be upregulation of adhesion molecules induced by this bacterial extract.
Adjuvants, Immunologic↗
Alloimmunization to platelet antigen HPA-1a (PIA1) is strongly associated with both HLA-DRB3*0101 and HLA-DQB1*0201.
Antibodies to the platelet HPA-1a antigen can elicit in the newborn a condition known as neonatal alloimmune thrombocytopenic purpura (NAITP). Previous studies based on RFLP analysis showed that 100% of HPA-1a-negative women who produced anti-HPA-1a antibodies (responders) were HLA-DRw52a (DRB3*0101). However, this specificity could also be found in some HPA-1a-negative women not producing anti-HPA-1a antibodies (nonresponders). We have analyzed in detail by PCR-SSOP the HLA-DR, -DQ, and -DP loci of 36 responders and 10 nonresponders. We found that while the allele DRB3*0101 was present in the vast majority of responders (91%), there were exceptions. Furthermore, the DQB1*0201 allele was found to be present in almost all responders (94%), but again was also found in nonresponders. The risk of alloimmunization to HPA-1a in an HPA-1b homozygous mother significantly increases with the presence of either allele, the odds ratio being 39.7 for DQB1*0201 and 24.9 for DRB3*0101. Sequencing of exon 2 of these two alleles from responders indicated no sequence difference when compared with the consensus sequences. This indicates that they do not represent variants when compared with the same alleles found in some nonresponders.
Alleles↗
Echocardiographic "smoke" is produced by an interaction of erythrocytes and plasma proteins modulated by shear forces.
OBJECTIVES: This study was designed to determine the blood elements responsible for spontaneous echocardiographic contrast. BACKGROUND: Spontaneous contrast or "smoke" is an echocardiographic image usually found in low flow conditions. Two blood elements, erythrocytes and platelets, have been related to the generation of smoke. METHODS: The echogenicity of porcine blood products was assessed in static and flow conditions and was graded on a digitized videodensity computer program that assigned a score of 0 for black and 100 for white images. Blood elements were circulated from a small tube (4-mm diameter) into a larger cylindric chamber (30-mm diameter) under controlled flow rate conditions. The following blood products were studied: whole blood, platelet-depleted blood, platelet-rich plasma, platelet-poor plasma, erythrocytes suspended in saline solution, adenosine diphosphate (ADP) added to platelet-rich plasma, and saline solution as a control medium. RESULTS: As blood flow was increased in 30 ml/min increments from 0 to 180 ml/min, whole blood echo videodensity (scale 0 to 100) progressively decreased in the larger tube from 38 and 42 to 20, 12, 14, 16 and 14, respectively. When flow increased from 0 to 30 ml/min in the smaller tube, corresponding to a wall shear rate of 0 to 80 s-1, the blood entering the chamber was completely echolucent. The echogenicity of blood products in the larger tube was for static flow (0 ml/min) and high flow (180 ml/min), respectively: platelet-depleted blood = 36 and 14; platelet-rich plasma = 2 and 2; platelet-poor plasma = 0 and 0; erythrocytes in saline solution = 8 and 12; ADP added to platelet-rich plasma = 0 and 15; saline solution = 0 and 0. Because platelets alone were nonechogenic but platelet-depleted blood produced a flow-dependent echogenicity similar to that produced by whole blood, platelets may not be involved in the production of smoke. However, when platelets were aggregated by ADP, they were echogenic but in dense clumps and in a flow-independent pattern not typical of the smokelike images. Erythrocytes suspended in saline solution had an intermediate density image. CONCLUSIONS: Echogenic smoke appears to be due primarily to the interaction of red blood cells and plasma proteins at low flow and low shear rate conditions.
Animals↗
Susceptibility and resistance to autoimmunity following neonatal injection of semi-allogeneic spleen cells in rats.
A model of neonatal allotolerance was developed in rats. Brown-Norway (BN) neonates injected with semi-allogeneic (BN x Lewis) F1 hybrid spleen cells express a long-lasting chimerism and exhibit polyclonal B cell activation demonstrated by hyperimmunoglobulinemia affecting mainly IgE and IgG1, anti-laminin and anti-DNA autoantibodies as well as glomerulonephritis and anti-hapten antibodies. These abnormalities are autoregulated although the chimerism persists. In contrast, Lewis (LEW) neonates injected with semi-allogeneic (BN x LEW) F1 hybrid spleen cells exhibit a very short-lasting chimerism and transient activation of B cells, as reflected by increased allo-class II antigen expression, but do not develop an autoimmune disease. The autoimmune syndrome observed in BN rats is similar to that reported in mice during host-versus-graft reaction. Similarities between the drug-induced models of autoimmunity and allogeneic reactions in BN rats are also striking. The susceptibility of BN rats and the resistance of LEW rats to these autoimmune diseases might respectively reflect the involvement of TH2-like or of TH1-like subsets.
Animals↗
Microleakage--full crowns and the dental pulp.
Recent studies have described microleakage under full crowns cemented with several different cements. This study tested three different types of crown margin preparations--a chamfer, a shoulder, and a shoulder plus a bevel to determine whether or not the margin preparation could affect microleakage. All crowns were cemented with zinc phosphate cement. The crowns were tested for leakage in thermocycled dye. All crowns demonstrated significant leakage following the path of the dentinal tubules into the pulp. This could possibly be one of the causes of pulpal inflammation and even pulpal death under full crowns.
Crowns↗
Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor.
We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation--a single-center, prospective, randomized study.
We conducted a randomized, prospective study to determine the long-term effects of prophylactic OKT3 in cadaveric renal transplantation. In the first group of patients (n = 56) OKT3 (5 mg/day) was administered for the first 14 postoperative days in association with azathioprine (AZA) and low-dose steroids, cyclosporine (CsA) being introduced on day 11. The other group of patients (n = 52) received CsA from the first POD, together with AZA and steroids. Both protocols were identical from POD 14 on. The total number of infections was higher in OKT3 patients (124/1455 patient-months [P-M] vs. 68/1320 in CsA patients, P less than 0.001) without impact on patient survival (94.5% in OKT3 vs. 93% in CsA patients). OKT3 patients experienced a lower number of rejection episodes (61 per 1455 P-M of risk exposure vs. 81/1320 in CsA patients, P less than 0.05). In addition, the frequency of corticoresistant rejection episodes was lower in OKT3 patients (9 out of 61 vs. 24 out of 81 in CsA patients, P less than 0.05). This resulted in a trend toward improved overall graft survival (83% vs. 75%, P = 0.12) and in a significant increase in immunological graft survival (92% vs. 79%, P = 0.02) in OKT3 patients at 3 years. Taken together, these data suggest that prophylactic OKT3 therapy might have long-term beneficial effects in cadaveric renal transplantation.
Adult↗