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E Abraham

Publications and source records attributed to E Abraham.

At least 127 records · Page 7Linked to original sources
PubMed1992

Haemorrhage-induced alterations in function and cytokine production of T cells and T cell subpopulations.

Haemorrhage produces alterations in macrophage, T and B cell function. In order to better define the mechanism for the effects of blood loss on immune response, we examined function of and cytokine production by purified T cells, CD4+ and CD8+ subpopulations after blood loss. Whereas T and CD4+ cells from control, unhaemorrhaged animals produced no alteration in proliferation when added to cultures of mitogen-stimulated splenocytes from normal mice, proliferation was decreased when T or CD4+ cells from haemorrhaged mice were included. The addition of CD8+ cells from haemorrhaged animals to mitogen-stimulated cultures reduced proliferation by approximately 50% more than that found when CD8+ cells from control, unhaemorrhaged animals were included. Supernatants of mitogen-stimulated splenocytes from haemorrhaged mice contained significantly less IL-2 and interferon-gamma (IFN-gamma) than did those from control, unhaemorrhaged mice. CD4+ populations from haemorrhaged mice produced significantly more IL-10, and significantly less IFN-gamma, than did CD4+ cells from control, unhaemorrhaged mice. There were no significant differences in IL-2, IL-4, IL-10 or IFN-gamma production by CD8+ cells from haemorrhaged or control mice. The present experiments demonstrate that haemorrhage affects both CD4+ and CD8+ T cell subsets. In particular, haemorrhage appeared to activate CD4+, Th2 cells, with concomitant suppression of the Th1 subpopulation. These results provide a mechanism which may contribute to the alterations in cytokine production previously described to occur following blood loss.

Animals↗
PubMed1992

Effects of inverse ratio ventilation on cardiorespiratory parameters in severe respiratory failure.

Inverse ratio ventilation, with prolonged inspiratory times, appears to improve gas exchange and arterial oxygenation in patients with severe respiratory failure; however, in previous studies, pressure-controlled inverse ratio ventilation (PC-IRV), which uses a rapidly decelerating inspiratory flow pattern, was compared to conventional volume-controlled ventilation, which uses a constant inspiratory flow rate. Pressure-controlled ventilation (PCV), with a decelerating inspiratory flow pattern and conventional inspiratory-to-expiratory (I/E) ratios, also has been shown to produce improvement in PaO2 when compared to volume-controlled ventilation. It therefore is unknown if the potentially beneficial effects of PC-IRV are due to the reversal of I/E ratios or to the use of the rapidly decelerating inspiratory flow pattern. In order to investigate this issue, cardiorespiratory values were measured in ten patients with severe respiratory failure ventilated first with PCV, then PC-IRV, and finally with a second period of PCV. Tidal volume, respiratory rate, end-expiratory pressure, and fraction of oxygen in inspired gas (FIO2) were maintained at the same value for both ventilatory modalities. The PC-IRV was associated with significant increases in PaO2, arterial pH, and mean airway pressure. Significant decreases in pulmonary shunt fraction, PaCO2, and cardiac index were found with PC-IRV. No significant changes in tissue oxygen delivery or consumption occurred with either PCV or PC-IRV. These results demonstrate that inversion of conventional I/E ratios produces no significant improvement in the overall cardiorespiratory profile of critically ill patients. This study also suggests that the clinical utility of PC-IRV is limited except in the setting of the adult respiratory distress syndrome with hypoxemia or hypercapnia refractory to other therapeutic options.

Adult↗
PubMed1992

Modulation of the posthemorrhage bacterial polysaccharide antigen-specific antibody response by interleukins 2 and 4.

Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Several studies have shown decreased release in vitro of interleukin-2 (IL-2) following blood loss. To better define in vivo the interactions between T and B cells, as well as the effects of treatment with the T cell-derived cytokines IL-2 and IL-4, mice were injected with concanavalin A at predetermined times posthemorrhage, and the percentages and numbers of splenic plasma cells producing antibody to the bacterial polysaccharide antigen levan (from Aerobacter levanicum) were determined. Decreased numbers and percentages of levan specific splenic plasma cells were found in animals treated with concanavalin A both immediately and 2 to 4 days after hemorrhage. Treatment in vivo with recombinant IL-2, but not IL-4 or anti-IL-2 receptor antibodies, following blood loss was able to increase the numbers of levan specific plasma cells to levels as high or higher than those found in normal, unhemorrhaged animals, but was unable to affect the decreased percentage of levan specific splenic plasma cells. These results suggest that the use in vivo of IL-2 may restore bacterial antigen specific antibody responses to normal levels after blood loss.

Animals↗
PubMed1991

Oral immunization with bacterial polysaccharide and adjuvant enhances antigen-specific pulmonary secretory antibody response and resistance to pneumonia.

Nosocomial pneumonia, often due to Pseudomonas aeruginosa, occurs frequently after haemorrhage and trauma, and contributes to the increased incidence of morbidity and mortality in this clinical setting. In order to determine if enhancement of bacterial antigen-specific secretory IgA (sIgA) titres in the lungs can increase resistance to P. aeruginosa pneumonia following haemorrhage, we investigated oral immunization strategies, using bacterial polysaccharides (levan, from Aerobacter levanicum, and P. aeruginosa polysaccharide type I) and adjuvant (cholera toxin and the B-subunit of cholera toxin), capable of increasing bacterial polysaccharide-specific pulmonary secretory antibody titres. Oral co-administration of 1000 micrograms levan and 10 micrograms cholera toxin resulted in increased titres of levan-specific sIgA in lung lavages and increased numbers of levan-specific pulmonary plasma cells, but no changes in serum anti-levan titres. Similarly, oral co-administration of 1000 micrograms P. aeruginosa polysaccharide and 10 micrograms cholera toxin produced increased anti-P. aeruginosa polysaccharide titres in lung lavages. Significant decreases in anti-levan pulmonary sIgA titres and in numbers of levan-specific pulmonary plasma cells were found when oral immunization with levan and cholera toxin was performed 4 days following haemorrhage, but not if the mice were immunized 8 h after blood loss. Although haemorrhage markedly increased the susceptibility of mice to P. aeruginosa pneumonia, significant protection from mortality could be achieved through oral immunization with 1000 micrograms P. aeruginosa polysaccharide and 10 micrograms cholera toxin 8 h after haemorrhage. These results demonstrate that haemorrhage induces marked alterations in bacterial antigen-specific pulmonary B-cell responses, which contribute to the increased susceptibility to infection in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Physiologic stress and cellular ischemia: relationship to immunosuppression and susceptibility to sepsis.

Multiple organ system failure secondary to infection is the most frequent cause of late mortality after hemorrhage, burns, and trauma. Although multiple immunologic abnormalities have been identified following injury, blood loss, and tissue ischemia, the mechanisms that produce these alterations in T- and B-cell function have not been completely defined. Physiologic stress and ischemia result in increased release of neuroendocrine peptides and hormones, capable of affecting normal neuroendocrine-immunologic balance and producing immunosuppression. Tissue ischemia leads to increased expression of heat shock proteins by hypoperfused cells, which can alter T-cell function. Injury also is followed by the appearance of serum immunosuppressive factors, which have been shown to inhibit T- and B-cell function. Future therapies directed at these and other cellular and molecular abnormalities initiated by tissue hypoperfusion may reverse the immunosuppressed state in critically ill patients and lead to improved outcome in this setting.

Animals↗
PubMed1991

Effects of hemorrhage and resuscitation on bacterial antigen-specific pulmonary plasma cell function.

BACKGROUND AND METHODS: Nosocomial pneumonia is frequent after hemorrhage and trauma, and often contributes to multiple organ system failure, morbidity, and mortality in this setting. Although the percentages and numbers of resting pulmonary B cells (clonal precursors) able to be stimulated to produce antibodies to bacterial antigens are markedly decreased after hemorrhage, the effects of hemorrhage on the pulmonary plasma cells actually producing antibody to bacterial antigens have not been examined. To investigate this question, mice were bled 30% blood volume, then resuscitated with the shed blood 1 hr later. At predetermined times after hemorrhage, the mice were intranasally immunized with liposomes containing the bacterial polysaccharide antigen levan (from Aerobacter levanicum). One week later, lung lavages were performed to measure bacterial antigen-specific secretory immunoglobulin A (sIgA) titers and the numbers of intraparenchymal pulmonary plasma cells producing antibody against the bacterial antigen were determined. RESULTS: Reduced numbers of pulmonary plasma cells producing antibody against the immunizing bacterial polysaccharide antigen were found between 1 and 14 days after blood loss, and titers of bacterial antigen-specific secretory IgA were decreased for greater than 2 wks after hemorrhage. The importance of these abnormalities in pulmonary B-cell function was demonstrated by an increased susceptibility to Pseudomonas aeruginosa pneumonia in mice infected 4 days after hemorrhage, when bacterial antigen-specific pulmonary plasma cell numbers were at their lowest point. Resuscitated mice showed the same increased susceptibility to P. aeruginosa pneumonia as did hemorrhaged but unresuscitated animals. CONCLUSIONS: Hemorrhage, even if resuscitated, results in alterations in bacterial antigen-specific pulmonary B-cell function and secretory IgA production that are profound, long lasting, and associated with increased susceptibility to infection at this mucosal surface. Because these effects on pulmonary B-cell function do not occur immediately after hemorrhage, immunization techniques able to enhance bacterial antigen-specific secretory IgA titers at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss.

Animals↗
PubMed1991

Failure of falciparum malaria prophylaxis by mefloquine in travelers from West Africa.

Due to the spread of chloroquine-resistant strains of Plasmodium falciparum in French speaking parts of Africa, we have found it necessary to prescribe mefloquine for antimalaria prophylaxis to travelers to this area. Weekly doses of 125 or 250 mg have been recommended for short journeys. In spite of this regimen, 16 documented cases of falciparum malaria in travelers have been recorded in the Bordeaux hospital center since October, 1988. Fifteen of these patients were tourists returning from West African countries, and one was an Ivorian student who had been on vacation to his home country. Nine of these patients were evaluated and found to have high plasma mefloquine levels. This report strongly supports the existence of mefloquine-resistant falciparum malaria in West Africa, especially in Sierra Leone, Burkina Faso, and Cote d'Ivoire.

Adult↗
PubMed1991

Effects of stress on cytokine production.

Physiologic stress results in significant alterations in the release of multiple cytokines. Increased production of interleukin-1 (IL-1) occurs following hemorrhage and thermal injury. Hemorrhage, accidental trauma and burns are followed by decreased interleukin-2 (IL-2) generation. Production of interleukin-3 (IL-3) and interleukin-5 (IL-5) is diminished following hemorrhage. Gamma-interferon release appears to be increased following hemorrhage. Stress secondary to infection is accompanied by marked elevations in serum levels of tumor necrosis factor (TNF), which contribute to hypotension and physiologic instability in this setting. Alterations in cytokine release probably play important roles in mediating alterations in immunologic, hemodynamic and cardiorespiratory function known to occur following physiologic stress. The production of all cytokines so far examined is altered by stress. Increased generation of IL-1, and probably of TNF and IL-6, contributes to the acute-phase reaction and hypermetabolic response which accompanies injury, burns, hemorrhage, and overwhelming infection. Severe immunosuppression, involving both T and B cell function, and contributing to the increased incidence of infection after injury may result, at least in part, from the multiple actions of stress-induced alterations in interleukin release. T cell activation is clearly affected by injury-induced decreases in IL-2, IL-3, and IFN-gamma release. Similarly, the depressed generation of systemic and mucosal antibodies to bacterial antigens following injury may be affected by alterations in the production of cytokines affecting B cell function, namely IL-1, IL-2, IL-3, IL-5 and IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hemorrhage in mice produces alterations in pulmonary B cell repertoires.

Nosocomial pneumonia occurs frequently after hemorrhage and trauma and contributes to the increased incidence of morbidity and mortality after severe injury. The production of secretory antibodies by mucosally associated B cells is an important component of pulmonary host defense mechanisms. To determine the effects of hemorrhage on pulmonary B cell function, we examined hemorrhage induced alterations in pulmonary B cell repertoires. There were no changes in the relative distribution of T or B cells among intraparenchymal pulmonary lymphocytes after blood loss. Hemorrhage induced decreases of between 5- and 10-fold in the frequencies and numbers of pulmonary B cell clonal precursors specific for the bacterial Ag levan and Pseudomonas aeruginosa polysaccharide. These decreases in numbers and frequencies of bacterial Ag-specific pulmonary B cell clonal precursors were present between 3 and 10 days after blood loss. Similar decreases in numbers and frequencies were found among pulmonary clonal precursors specific for the autoantigen mouse transferrin, but not for the autoantigen dsDNA or the external antigens OVA and keyhole limpet hemocyanin. These results demonstrate that hemorrhage produces marked alterations in pulmonary B cell repertoires, which may contribute to postinjury abnormalities in host defenses.

Animals↗
PubMed1990

Purification and characterization of intraparenchymal lung lymphocytes.

We analyzed phenotypic and functional characteristics of intraparenchymal pulmonary lymphocytes in mice. As determined by flow cytometry, approximately 30% more T cells than B cells were found. Nearly all T cells bore the alpha beta TCR, most of which stained with either CD4+ or CD8+, although small numbers of double-negative T cells were present; the CD8+/CD4+ ratio was approximately 0.37. While practically all B cells bore surface IgM, and no IgA+ cells were found, and approximately more than 80% of the plasma cells produced IgA. Approximately half of the LPS-responsive cells produced IgA. Pulmonary B cell clonal precursors specific for the autoantigen, transferrin, were present in higher frequencies than those specific for the bacterial antigens, levan and Pseudomonas aeruginosa polysaccharide type I, or those producing antibodies against OVA. These results demonstrate that a distinct population of lymphocytes is present in the lungs.

Animals↗
PubMed1990

Selective reminiscences of beta-lactam antibiotics: early research on penicillin and cephalosporins.

The discovery, made in Oxford, that crude penicillin could cure systemic and life-threatening bacterial infections was followed by attempts to purify penicillin, to determine its structure and then to produce it by total chemical synthesis. The beta-lactam structure of the molecule, first proposed in October 1943, was a source of controversy until 1945. However, no useful chemical synthesis was achieved and fermentation became the commercial source of the antibiotic. In 1953, one of the products of a Cephalosporium sp. from Sardinia was shown to be a new and hydrophilic penicillin (penicillin N). This was contaminated with a substance having the same side-chain but a characteristic absorption spectrum. The latter, cephalosporin C, showed antibacterial activity but was not inactivated by a penicillinase. The determination of its beta-lactam structure and isolation of its nucleus enabled pharmaceutical companies to produce many semisynthetic cephalosporins. A new tripeptide was later found to be an intermediate in the biosynthesis of both penicillin N and cephalosporin C, and this was followed by the complete elucidation of the biosynthetic pathways leading to these compounds and to benzylpenicillin.

Cephalosporins↗
PubMed1990

Hemorrhage in mice produces alterations in intestinal B cell repertoires.

Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Infections occurring after injury often originate in the intestine. In order to determine the effects of hemorrhage on intestinal B cell function, we examined hemorrhage-induced alterations in available (clonal precursors) and actual (plasma cells) B cell repertoires among intestinal lamina propria and Peyer's patch cells. Hemorrhage resulted in complete suppression of the increase in levan-specific lamina propria and Peyer's patch plasma cell numbers following oral immunization with this bacterial polysaccharide antigen. The absolute frequency of clonal precursors specific for levan among lamina propria B cells decreased by more than twofold following hemorrhage. These results demonstrate that hemorrhage produces marked alterations in intestinal B cell repertoires, which may contribute to postinjury abnormalities in host defenses.

Animals↗
PubMed1990

Immunoglobulin VH gene expression following hemorrhage.

Hemorrhage has multiple effects on immunologic response, including alteration of B cell repertoires. In limiting dilution studies, decreased absolute frequencies of splenic clonal precursors specific for bacterial antigens were found after blood loss. In order to better define the effects of hemorrhage on B cell function, we examined immunoglobulin VH gene family expression following blood loss using both in situ hybridization and the RNA colony blot technique. No changes in VH gene family utilization were found after hemorrhage. These results demonstrate that the hemorrhage induced alteration in B cell function involves all VH gene families, without modifying distributive frequencies in VH gene family expression.

Animals↗
PubMed1990

Transfer of T or CD8+ cells from hemorrhaged mice produce alterations in bacterial antigen specific plasma cell repertoires in normal syngeneic recipients.

Hemorrhage has multiple effects on immunologic response, including alteration of B cell repertoires and T cell function. This study examined possible relationships between these two phenomena by determining the effects of T cells and T cell subsets transferred from hemorrhaged donors into normal, unhemorrhaged syngeneic recipients on B cell repertoires. Mice given total T or CD8+ cells from hemorrhaged animals then immunized with the bacterial polysaccharide antigen levan had a decreased percentage of plasma cells producing antibody to levan compared to that in mice given T or CD8+ cells from unhemorrhaged animals. These effects of post hemorrhage CD8+ cells were not seen after transfer into nu/nu mice, indicating that these cells did not directly affect B cell function, but rather required other T cell populations in order to alter the B cell repertoire. These results demonstrate that hemorrhage-induced alterations in bacterial antigen specific B cell repertoires may result from T and CD8+ cell mediated changes in T-B interactions.

Animals↗
PubMed1990

Effects of intravenous immunoglobulin on hemorrhage-induced alterations in plasma cell repertoires.

Hemorrhage produces decreases in serum immunoglobulin (Ig) levels and alterations in the number and frequency of B cells producing antibodies against bacterial antigens. These abnormalities in immune response may contribute to the increased susceptibility to infection after injury and hemorrhage. To examine the relationship between serum Ig levels and bacterial antigen-specific plasma cell numbers and frequencies after blood loss, we treated hemorrhaged mice with intravenous Ig (IVIG). Hemorrhaged mice given IVIG had increased total numbers of splenic plasma cells compared with normal or hemorrhaged, untreated mice. Immunization with the bacterial polysaccharide antigen levan immediately after hemorrhage resulted in approximately 60% fewer levan-specific splenic plasma cells than those seen in normal unhemorrhaged mice. Treatment of hemorrhaged mice with IVIG did not correct the decrease in levan-specific plasma cells. These results demonstrate that hemorrhage-induced alterations in the numbers and frequencies of bacterial antigen-specific B cells are not related to changes in serum Ig levels and cannot be corrected through administration of IVIG.

Animals↗