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L Grinberg

Publications and source records attributed to L Grinberg.

At least 19 recordsLinked to original sources
PubMed1998

Transgenic mice expressing human fetal globin are protected from malaria by a novel mechanism.

Studies in vitro by Pasvol et al (Nature, 270:171, 1977) have indicated that the growth of Plasmodium falciparum in cells containing fetal hemoglobin (HbF = alpha2gamma2) is retarded, but invasion is increased, at least in newborn cells. Normal neonates switch from about 80% HbF at birth to a few percent at the end of the first year of life. Carriers of beta-thalassemia trait exhibit a delay in the normal HbF switch-off, which might partially explain the protection observed in populations with this gene. To study this hypothesis in vivo, we used transgenic (gamma) mice expressing human Agamma and Ggamma chains resulting in 40% to 60% alpha2Mgamma2 hemoglobin, infected with rodent malaria. Two species of rodent malaria were studied. P chabaudi adami causes a nonlethal infection, mainly in mature red blood cells (RBC). P yoelii 17XNL is a nonlethal infection, invading primarily reticulocytes, whereas P yoelii 17XL is a lethal variant of P yoelii 17XNL and causes death of mice in approximately 1 to 2 weeks. Data indicate that this strain may cause a syndrome resembling cerebral malaria caused by P falciparum (Am J Trop Med Hyg, 50:512, 1994). In gamma transgenic mice infected with P chabaudi adami, the parasitemia rose more quickly (in agreement with Pasvol) than in control mice, but was cleared more rapidly. In mice infected with P yoelii 17XNL, a clear reduction in parasitemia was observed. Interestingly, splenectomy before this infection, did not reverse protection. The most striking effect was in lethal P yoelii 17XL infection. Control mice died between 11 to 13 days, whereas gamma mice cleared the infection by day 22 and survived, a phenomenon also observed in splenectomized animals. These results suggest that HbF does indeed have a protective effect in vivo, which is not mediated by the spleen. In terms of mechanisms, light microscopy showed that intraerythrocytic parasites develop slowly in HbF erythrocytes, and electron microscopy showed that hemozoin formation was defective in transgenic mice. Finally, digestion studies of HbF by recombinant plasmepsin II demonstrated that HbF is digested only half as well as hemoglobin A (HbA). We conclude that HbF provides protection from P falciparum malaria by the retardation of parasite growth. The mechanism involves resistance to digestion by malarial hemoglobinases based on the data presented and with the well-known properties of HbF as a super stable tetramer. In addition, the resistance of normal neonates for malaria can now be explained by a double mechanism: increased malaria invasion rates, reported in neonatal RBC, will direct parasites to fetal cells, as well as F cells, and less to the approximately 20% of HbA containing RBC, amplifying the antimalarial effects of HbF.

Animals↗
PubMed1998

Enhanced protective antibody responses to PspA after intranasal or subcutaneous injections of PspA genetically fused to granulocyte-macrophage colony-stimulating factor or interleukin-2.

Antibody to pneumococcal surface protein A (PspA) has been shown to be protective for Streptococcus pneumoniae infections in mice. In an attempt to define a model for inducing protective antibody to PspA in the absence of adjuvant, we designed two genetic fusions, PspA-interleukin-2 [IL-2]) and PspA-granulocyte-macrophage colony-stimulating factor (GM-CSF). These constructs maintained high cytokine function in vitro, as tested by their activity on IL-2 or GM-CSF-dependent cell lines. While intranasal immunization with PspA induced no detectable anti-PspA response, both PspA-IL-2 and PspA-GM-CSF stimulated high immunoglobulin G1 (IgG1) antibody responses. Interestingly, only the PspA-IL-2, not the PspA-GM-CSF, construct stimulated IgG2a antibody responses, suggesting that this construct directed the response along a TH1-dependent pathway. Comparable enhancement of the anti-PspA response with similar isotype profiles was observed after subcutaneous immunization as well. The enhancement observed with PspA-IL-2 was dependent on IL-2 activity in that it was not seen in IL-2 receptor knockout mice, while PspA in alum induced high-titer antibody in these mice. The antibody was tested for its protective activity in a mouse lethality model using S. pneumoniae WU-R2. Passive transfer of 1:90 dilutions of sera from mice immunized with PspA-IL-2 and PspA-GM-CSF elicited protection of CBA/N mice against intravenous challenge with over 170 50% lethal doses of capsular type 3 strain WU2. Only 0.17 microg or less of IgG antibody to PspA was able to provide passive protection against otherwise fatal challenge with S. pneumoniae. The data demonstrate that designing protein-cytokine fusions may be a useful approach for mucosal immunization and can induce high-titer systemic protective antibody responses.

Administration, Intranasal↗
PubMed1998

New solution for prolonged myocardial preservation for transplantation.

BACKGROUND: A solution for prolonged cold storage of the heart has been developed. The Jerusalem-Cape Town Solution (JCT) is an "intracellular" type cardioplegic solution and is formulated to (1) minimize hypothermic-induced cell swelling, (2) diminish intracellular acidosis, (3) prevent the expansion of the interstitial space during the reperfusion, (4) protect against oxygen free radical injury during early reperfusion, and (5) provide substrates for regenerating high-energy phosphates. METHODS: With a Langendorff model, rat hearts were subjected to 15 minutes of perfusion with Krebs-Henseleit, 10 minutes of cardioplegic infusion and 20 hours of cold storage (5 degrees to 6 degrees C). Hearts were reperfused for 60 minutes and hemodynamic recovery was assessed. The hearts were assigned to three groups (eight hearts in each), according to the cardioplegic solution used: group 1, JCT; group 2, Bretschneider's HTK cardioplegic solution; and group 3 University of Wisconsin cold storage solution. RESULTS: After 60 minutes of reperfusion, the recovery of the coronary artery flow in group 1 (JCT) was significantly better than in group 2, and slightly better than in group 3 (64% +/- 8.9%, 47.2% +/- 11.6%, 52.5% +/- 19.9%, mean +/- SD, respectively; group 1 versus group 2, p < 0.01). The recovery of the left ventricular developed pressure (LVDP) was significantly better in group 1 compared with group 2 and group 3 (60.2% +/- 14.5%, 41.1% +/- 12.6% and 36.5% +/- 10.1%, respectively; p < 0.01). The recovery of the heart contractility expressed by the product of LVDP and the heart rate (LVDP x heart rate) was significantly higher in group 1 than in group 2 and group 3 (47.5% +/- 3.4%, 23.6% +/- 9.6%, and 28.7% +/- 8.3%, respectively, p < 0.001). In hearts stored for 12 hours in JCT or HTK, the recovery of the heart contractility did not differ significantly (73.4% +/- 12.7% or 70.8% +/- 30.8%, respectively). Modified reperfusion aimed to improve postischemic heart recovery did not bring significant changes in cardiac mechanical function but resulted in an increase in postischemic coronary artery flow recovery in hearts reperfused with amino acid-enriched buffer. CONCLUSIONS: The JCT solution is effective (as well as HTK) in preserving the ischemic hearts for up to 12 hours. It is superior to HTK or University of Wisconsin solution at 20 hours of isolated ischemic storage.

Adenosine Triphosphate↗
PubMed1997

Is the transference feared by the psychoanalyst?

The author considers whether the reason for the variety and multiplicity of theories about the transference might lie in analysts' fears of its dangers. He reviews Freud's development of the concept from its origins, when it was seen as resistance, to its use as a fundamental instrument of the treatment, and lays particular emphasis on its perception as a burden. Classical and later authors' conflicting views of the transference and its management are surveyed in the light of the common ground otherwise existing between schools. Views of the negative transference are also presented. Some clinical vignettes are given, showing the analyst responding to the patient's transference, grappling with his own countertransference feelings and using them to illuminate the clinical situation. The author emphasises the importance of the analyst's training and experience in enabling him to withstand the regressive onslaught of the patient's projections without resorting to theory-related or technical defensive measures. In his view, the transference is not in itself a resistance but may be used as such. The analyst must not interpret merely in order to get rid of the anxiety aroused in himself by the patient's regressive feelings. The paper ends with a consideration of the importance of intuition, the countertransference and sublimated projective counter-identification.

Depressive Disorder↗
PubMed1995

Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo.

Red blood cell (RBC) membranes from patients with the thalassemic and sickle hemoglobinopathies carry abnormal deposits of iron presumed to mediate a variety of oxidative-induced membrane dysfunctions. We hypothesized that the oral iron chelator deferiprone (L1), which has an enhanced capacity to permeate cell membranes, might be useful in chelating these pathologic iron deposits from intact RBCs. We tested this hypothesis in vitro by incubating L1 with RBCs from 15 patients with thalassemia intermedia and 6 patients with sickle cell anemia. We found that removal of RBC membrane free iron by L1 increased both as a function of time of incubation and L1 concentration. Thus, increasing the time of incubation of thalassemic RBCs with 0.5 mmol/L L1 from 0.5 to 6 hours, enhanced removal of their membrane free iron from 18% +/- 9% to 96% +/- 4%. Dose-response studies showed that incubating thalassemic RBC for 2 hours with L1 concentrations ranging from 0.125 to 0.5 mmol/L resulted in removal of membrane free iron from 28% +/- 15% to 68% +/- 11%. Parallel studies with sickle RBCs showed a similar pattern in time and dose responses. Deferoxamine (DFO), on the other hand, was ineffective in chelating membrane free iron from either thalassemic or sickle RBCs regardless of dose (maximum, 0.333 mmol/L) or time of incubation (maximum, 24 hours). In vivo efficacy of L1 was shown in six thalassemic patients whose RBC membrane free iron decreased by 50% +/- 29% following a 2-week course of L1 at a daily dose of 25 mg/kg. As the dose of L1 was increased to 50 mg/kg/d (n = 5), and then to 75 mg/kg/d (n = 4), 67% +/- 14% and 79% +/- 11%, respectively, of their RBC membrane free iron was removed. L1 therapy--both in vitro and in vivo--also significantly attenuated the malondialdehyde response of thalassemic RBC membranes to in vitro stimulation with peroxide. Remarkably, the heme content of RBC membranes from L1-treated thalassemic patients decreased by 28% +/- 10% during the 3-month study period. These results indicate that L1 can remove pathologic deposits of chelatable iron from thalassemic and sickle RBC membranes, a therapeutic potential not shared by DFO. Furthermore, membrane defects possibly mediated by catalytic iron, such as lipid peroxidation and hemichrome formation, may also be alleviated, at least in part, by L1.

Anemia, Sickle Cell↗
PubMed1987

Dreams and acting out.

Dreams can be used as containers that free patients from increased tension. This may be the principal function of certain types of dreams, called "evacuative dreams." They are dreams used for getting rid of unbearable affects and unconscious fantasies, or as a safety valve for partial discharge of instinctual drives. These dreams are observed primarily in borderline and psychotic patients, but can also be seen in the regressive states of neurotic patients during weekends and other periods of separation. Such dreams have to be differentiated from "elaborative dreams," which have a working-through function and stand in an inverse relationship to acting out: the greater the production of elaborative dreams, the less the tendency to act out, and vice versa.

Acting Out↗
PubMed1984

A psychoanalytic study of migration: its normal and pathological aspects.

Without maintaining that it always follows the same steps, we could say that the migratory process passes through several phases. The feelings that prevail are those of intense sorrow for all that has been abandoned or lost, fear of the unknown, and the very profound experiences of loneliness, privation, and helplessness. Paranoid, confusional, and depressive anxieties occupy the scene in turn. This stage may be followed or replaced by a manic state in which the immigrant minimizes the transcendental significance of the change in his life or, on the contrary, magnifies the advantages of the change and overvalues everything in the new situation, disdaining what has been lost. After a variable period of time, nostalgia appears, and sorrow for the lost world. The immigrant begins to recognize feelings previously dissociated or denied and becomes capable of "suffering" his pain ("growing pains") while, at the same time, he becomes more accessible to the slow and progressive incorporation of elements of the new culture. The interaction between his internal and external world becomes more fluid. Recovery of the pleasure of thinking and desiring and of the capacity for making plans for the future, in which the past is regarded as such and not as a "lost paradise" where one constantly longs to return. In this period, it could be considered that mourning for the country of origin has been worked through to the maximum extent possible, facilitating integration of the previous culture into the new culture, without the need to renounce the old. All of this promotes an enrichment of the ego and the consolidation of a more evolved sense of identity.

Acculturation↗
PubMed1984

The influence of Cervantes on the future creator of psychoanalysis.

Our work is intended to recreate the origins of the 'future creator of psychoanalysis'. Cervantes had a decisive influence on Freud. Don Quixote occupied a central place during a period which we consider to be crucial in the creation of psychoanalysis; we refer to the summer of 1883 during which Freud confessed to Martha that he had become more interested in this book than in brain anatomy. In this work, Cervantes delves in-depth into problems which he had set out in The Colloquy of the Dogs, read by Freud in his adolescence when he was learning Spanish and which confronted some of the great psychoanalytic themes such as reality-fantasy, language, instinct and reason, traumatic situations, 'family romance', etc. These themes appear in a psychoanalytically structured dialogue in which one of the dogs, Berganza, tells his life story (in the form of catharsis) to the other dog, Cipión, with whom Freud identified himself. Basically, it is the psychotherapeutic model that Freud used with his own hysterical patients. Another dialogue which was essential for Freud was that of Don Quixote and Sancho Panza, due to the following major reasons (as well as others): For the clear discrimination between reality and fantasy as well as their interplay. Because madness is presented as a complex phenomenon, but intelligible in terms of human motives. For the penetrating description of the transition in Don Quixote from mania to depression. Because at that moment of his life, Freud himself was living through a personal conflict between his dreams of carrying out some scientific feat and the demands of attending to his mundane necessities.

Austria↗