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Biomedical subjects

E Abraham

Publications and source records attributed to E Abraham.

At least 91 records · Page 5Linked to original sources
PubMed1996

Plasma from hemorrhaged mice activates CREB and increases cytokine expression in lung mononuclear cells through a xanthine oxidase-dependent mechanism.

Hemorrhage rapidly increases plasma xanthine oxidase levels as well as the expression of proinflammatory and immunoregulatory cytokines in the lungs. To determine the role of circulating xanthine oxidase (XO), as well as other plasma factors, in affecting pulmonary cytokine expression, we conducted studies in which plasma from hemorrhaged mice was transferred into unhemorrhaged recipient mice. Administration of posthemorrhage plasma to recipient mice increased the levels of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) in lung mononuclear cells. No enhancement of mRNA levels for these cytokines was found in the lungs of mice given allopurinol-treated posthemorrhage plasma or fed a tungsten-enriched, XO-depleting diet prior to transfer of posthemorrhage plasma. Among the nuclear transcriptional regulatory factors examined, only the cyclic AMP response-element binding protein (CREB) was activated in nuclear extracts from lung mononuclear cells of mice that were given posthemorrhage plasma. No activation of nuclear factor-kappa B (NF-kappa B), nuclear factor interleukin 6 (NF-IL6), activating protein-1 (AP-1), or serum protein-1 (SP-1) was found. These results suggest that the mechanism for hemorrhage-induced increases in pulmonary cytokine expression is by activation of the enhancer CREB through a tissue XO-dependent pathway initiated by plasma-borne mediators.

Allopurinol↗
PubMed1996

WAIS-R verbal-performance IQ discrepancies in persons with lateralized lesions: utility of a seven subtest short form.

WAIS-R Verbal-Performance IQ difference scores for Ward's (1990) seven subtest short form and the complete WAIS-R were examined in patients with lateralized and diffuse lesions. For both versions, the expected Performance > Verbal pattern was observed in the right hemisphere lesion group, while no summary score differences were seen in the left hemisphere group. Verbal-Performance IQ discrepancies for the short form fell within +/- 5 points of the WAIS-R discrepancy scores in about 75%of the cases, regardless of lesion location. Statistically reliable IQ differences between the complete and abbreviated WAIS-R attained 66%, 91%, and 89% agreement for the left, right, and diffuse groups, respectively. The results support the clinical utility of the seven subtest short form.

Journal Article↗
PubMed1996

Alterations in transcriptional regulation of proinflammatory and immunoregulatory cytokine expression by hemorrhage, injury, and critical illness.

Transcriptional factors which bind to the promoter regions of genes play an important role in regulating gene expression. The transcription of immunoregulatory and proinflammatory cytokines as well as other proteins known to be important in producing organ system injury after trauma, blood loss, or sepsis is controlled both by the activation of transcriptional regulatory factors and by the interactions of these transcriptional factors with each other, resulting in augmentation or suppression of gene transcription. Most of the transcriptional factors which appear to play a role in modulating immune response in the setting of critical illness can be activated through several different pathways, often involving intracellular redox state and cytokine or endotoxin interaction with membrane receptors. In the severely injured patient, many of these activating mechanisms appear to be operative. Modulation of gene transcription, particularly in those organ systems (e.g., the lungs) which are most vulnerable to inflammatory injury, may be an important therapeutic target in critically ill patients.

Animals↗
PubMed1995

Human papillomaviruses in 91 oral cancers from Indian betel quid chewers--high prevalence and multiplicity of infections.

India has one of the world's highest incidences of oral cancer. The habit of chewing betel quid is widespread and is suspected to play a role in the etiology of this disease. Studies in many other countries have also pointed to a role for human papilloma-viruses (HPVs) in the etiology of some oral cancers. In this study we analyzed biopsies from 91 Indian oral cancer patients, most of whom were betel quid chewers, by PCR amplification and direct DNA sequencing. HPV DNA was detected in 74% of these lesions, of which 41% had multiple HPV infections. Among the lesions from different oral sites, lesions of the tongue had the highest rate (9 of 11) of HPV infection. These HPV prevalences are among the highest ever reported in oral cancers. As to individual HPV types, prevalences of HPV-6, HPV-11, HPV-16 and HPV-18 were 13%, 20%, 42% and 47%, respectively. No additional known or novel HPV types were detected. To understand the unexpectedly high prevalences of the "low-risk" types HPV-6 and HPV-11, we compared the subtypes and variants that were found in oral cancers against those from benign genital warts from the same patient population but found no differences. The high prevalence of HPV in the oral cancers of these Indian patients suggests that viral infection is an important etiological component, with betel quid probably causing additional mutagenic steps in the carcinogenic process.

Areca↗
PubMed1995

Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

Acyltransferases↗
PubMed1995

Effects of treatment with the 21-aminosteroid, U7438F, on pulmonary cytokine expression following hemorrhage and resuscitation.

OBJECTIVE: To determine the effects of therapy with the antioxidant 21-aminosteroid, U74389F, on cytokine mRNA levels following hemorrhage and resuscitation. DESIGN: Prospective, controlled animal study. SETTING: University research laboratory. SUBJECTS: Male bronchoalveolar lavage B/c (BALB/c) mice. INTERVENTIONS: U74389F (10 mg/kg) in CS4 vehicle or CS4 vehicle alone, was administered intravenously to bronchoalveolar lavage B/c mice 15 mins before 30% blood volume hemorrhage, with resuscitation 60 mins later. MEASUREMENTS AND MAIN RESULTS: Semiquantitative polymerase chain reactions were used to determine the effects of therapy with U74389F on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, alveolar macrophages, and peripheral blood mononuclear cells obtained 2 hrs and 3 days after hemorrhage. In mice treated with U74389F, mRNA levels for interleukin (IL)-1 beta, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma were significantly decreased among intraparenchymal pulmonary mononuclear cells obtained 3 days, but not 2 hrs, after hemorrhage. No effects of therapy with U74389F were found in modulating posthemorrhage cytokine expression among alveolar macrophages or peripheral blood mononuclear cells. CONCLUSIONS: These studies demonstrate that treatment with U74389F, a 21-aminosteroid whose major activity is inhibition of lipid peroxidation due to the generation of reactive oxygen intermediates, significantly decreases hemorrhage-induced activation of proinflammatory cytokine expression among pulmonary cell populations. In addition, the present results, showing decreased expression of proinflammatory and immunoregulatory cytokines among intraparenchymal pulmonary mononuclear cells following treatment with U74389F, suggest that 21-aminosteroids may have clinical utility in preventing and/or modulating acute lung injury in the postinjury period.

Animals↗
PubMed1995

Contribution of tumor necrosis factor-alpha to pulmonary cytokine expression and lung injury after hemorrhage and resuscitation.

OBJECTIVE: To examine the role of tumor necrosis factor-alpha (TNF-alpha) in producing acute inflammatory lung injury after hemorrhage and resuscitation. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male BALB/c mice. INTERVENTIONS: Treatment with rat antimouse monoclonal anti-TNF-alpha antibodies or control rat immunoglobulin G 1 hr after 30% blood volume hemorrhage and resuscitation. MEASUREMENTS AND MAIN RESULTS: Therapy with monoclonal anti-TNF-alpha antibodies prevented the posthemorrhage increases in pulmonary TNF-alpha and interferon-gamma protein levels that normally occur after blood loss. Administration of monoclonal anti-TNF-alpha antibodies also diminished the increases in interleukin-1 beta, interleukin-6, and interleukin-10 mRNA, but not the increases in TNF-alpha and interferon-gamma mRNA, which are found in the lungs following hemorrhage. In addition, therapy with monoclonal anti-TNF-alpha antibodies was associated with significant improvement in the histologic parameters of posthemorrhage lung injury, particularly intra-alveolar hemorrhage and pulmonary vascular congestion. CONCLUSIONS: These results indicate that TNF-alpha has an important role in the development of acute inflammatory lung injury after blood loss. Blockade of TNF-alpha with monoclonal antibodies significantly reduces hemorrhage-induced lung injury.

Animals↗
PubMed1995

Xanthine oxidase-derived oxygen radicals increase lung cytokine expression in mice subjected to hemorrhagic shock.

Acute inflammatory lung injury often complicates hemorrhagic shock, a systemic ischemia-reperfusion syndrome. Because oxygen radicals are generated during ischemia-reperfusion, and oxygen radicals can activate nuclear regulatory factors that affect transcription of proinflammatory cytokines, we examined the premise that oxygen radicals increase interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) expression in lung mononuclear cells after hemorrhage. Intraparenchymal pulmonary mononuclear cells isolated 1 h after hemorrhage from control mice had increased levels of mRNA for IL-1 beta (P < 0.001) and TNF-alpha (P < 0.05) compared with cells from sham-hemorrhaged mice. Hemorrhaged mice treated with the oxygen radical scavenger dimethylthiourea (DMTU) had decreased levels of mRNA for IL-1 beta in pulmonary mononuclear cells, compared with hemorrhaged controls (P < 0.05). In hemorrhaged mice depleted of xanthine oxidase (XO) by a tungsten-enriched diet, pulmonary mononuclear cell mRNA levels for IL-1 beta and TNF-alpha were significantly decreased (P < 0.01 and 0.05, respectively), compared with cells from hemorrhaged control mice fed a normal diet. Similarly, mRNA transcripts for IL-1 beta and TNF-alpha among pulmonary mononuclear cells from hemorrhaged mice treated with allopurinol, an inhibitor of XO, were also significantly reduced (P < 0.05 and 0.001, respectively), compared with hemorrhaged control mice not treated with allopurinol. Our results indicate that XO-derived oxygen radicals contribute to the increased expression of mRNA for IL-1 beta and TNF-alpha, which occurs among pulmonary mononuclear cell populations immediately after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
PubMed1995

Hemorrhage and resuscitation alter the expression of ICAM-1 and P-selectin in mice.

Acute inflammatory lung injury is a common clinical occurrence following blood loss and trauma, and is characterized by massive neutrophil infiltration into the lung. In order to better examine cell trafficking that may contribute to lung injury in this setting, we investigated in vivo mRNA levels and immunohistochemically determined expression of the adhesion molecules P-selectin and the intercellular adhesion molecule (ICAM)-1 in murine lungs over the 3-day period following hemorrhage and resuscitation. Significant increases in P-selectin mRNA levels were present in lungs obtained 3 days after hemorrhage. ICAM-1 mRNA levels were significantly increased 6 and 72 hr after hemorrhage. Immunohistochemical staining for P-selectin was enhanced on pulmonary vascular endothelium in all visible vessels at 6, 24, and 72 hr after hemorrhage. ICAM-1 immunoreactivity was significantly increased on the alveolar epithelium at 6 and 72 hr post-hemorrhage. These results suggest that increased expression of adhesion molecules in the lung at early post-hemorrhage timepoints may contribute to neutrophil infiltration into the lungs and the frequent development of acute lung injury following blood loss and trauma.

Animals↗
PubMed1994

Intrathecal injection of cell-permeable analogs of cyclic 3',5'-guanosine monophosphate produces hyperalgesia in mice.

Several recent studies suggest that spinal cord levels of cyclic 3',5'-guanosine monophosphate (cGMP) may participate in the development of hyperalgesia. The purpose of this study was to directly evaluate whether cell permeable analogues of cGMP evoke a thermal hyperalgesia (using a hot-plate assay) when administered intrathecally in mice. Our results indicate that two cell permeable forms of cGMP evoke a dose dependent hyperalgesia when administered intrathecally in mice. Additionally, this hyperalgesia was selective since neither non-cell permeant cGMP nor guanosine had any effect on the latency of paw withdrawal when compared to the vehicle injected controls. These data indicate that cGMP is involved in the facilitation of thermal hyperalgesia at the level of the spinal cord.

Animals↗
PubMed1994

Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure.

OBJECTIVE: Volume-controlled ventilation is frequently chosen as the initial mode of ventilatory support in patients with hypoxic respiratory failure. Recent data, however, suggest that pressure-limited ventilation, using a rapidly decelerating flow delivery pattern, may produce a more desirable clinical effect through reduced peak airway pressures and increased static compliance, tissue oxygen delivery, and consumption. This study was performed to assess the feasibility and utility of early and sustained use of pressure-limited ventilation in patients with this clinical syndrome. DESIGN: Randomized, prospective trial. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: The study encompassed all patients (n = 27) receiving care in a medical ICU for acute, severe hypoxic respiratory failure (PaO2/FIO2 ratio of < 150) during a 6-month period. INTERVENTIONS: Ventilatory support via either pressure-limited or volume-controlled ventilation, initiated within 24 hrs of endotracheal intubation. MEASUREMENTS: On-line monitoring of the following ten ventilatory variables at 1-min intervals for 72 hrs or until extubation or death (maximum of 43,200 data points per patient): peak airway pressure, mean airway pressure, end-tidal CO2 concentration, CO2 minute excretion, inspiratory tidal volume, expiratory tidal volume, pause pressure, end-expiratory pressure, static thoracic compliance, and inspiratory resistance. Additionally, PaO2/FIO2 values and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded on a daily basis, as were significant clinical events and changes in ventilator settings. RESULTS: Although the severity of illness at study entry as determined by APACHE II score and PaO2/FIO2 was similar in patients treated with pressure-limited or volume-controlled ventilation, peak airway pressure was consistently lower in patients randomized to pressure-limited ventilation (p = .05 at 12 hrs postintubation). The use of pressure-limited ventilation also was associated with a more rapid increase in static compliance (p = .05) than that found with volume-controlled ventilation. There was a trend toward more rapid normalization of CO2 minute excretion in patients treated with pressure-limited ventilation. Pressure-limited treated patients who survived their illness and were extubated, required fewer days of mechanical ventilation than did patients randomized to volume-controlled treated ventilation (p = .05). No pneumothoraces occurred in any study patients. One volume-controlled patient developed subcutaneous emphysema. Pressure-limited ventilation was well tolerated, and sedation requirements were equivalent in the two groups. CONCLUSIONS: Pressure-limited ventilation can be used safely and is well tolerated as an initial mode of ventilatory support in patients with acute hypoxic respiratory failure. Because the early initiation of pressure-limited ventilation is associated with lower peak airway pressure and more rapid improvement in static thoracic compliance than volume-controlled ventilation, pressure-limited ventilation may have a beneficial role when used as the primary ventilatory modality in patients with this clinical condition.

Adult↗
PubMed1994

Cytokine, complement, and endotoxin profiles associated with the development of the adult respiratory distress syndrome after severe injury.

OBJECTIVE: The adult respiratory distress syndrome (ARDS) is a frequent complication after severe accidental trauma. This study examines the hypothesis that increased systemic concentrations of proinflammatory cytokines, endotoxin, or complement fragments may predict the development of ARDS. DESIGN: Prospective, observational study. SETTING: Two Level I university trauma centers. PATIENTS: Fifteen severely injured patients (Injury Severity Score of > or = 25). INTERVENTIONS: Standard emergency department, operating room, and intensive care unit management. MEASUREMENTS AND MAIN RESULTS: Plasma samples were obtained at 4-hr intervals from the time of injury and were assayed for concentrations of endotoxin, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and complement fragments C3a and C4a. Hemodynamic and oxygen metabolism variables also were measured at 4-hr intervals after injury. Seven patients developed ARDS and eight patients did not. The PaO2/FIO2 ratio was significantly decreased in the patients with ARDS compared with non-ARDS patients as early as 4 hrs postinjury, and remained significantly decreased throughout the initial 24 hrs after severe accidental injury. Plasma IL-8, IL-6, C3a, and C4a concentrations were markedly increased starting in the immediate postinjury period in both ARDS and non-ARDS patients, but no significant differences were found between the two groups until 16 hrs after injury when plasma IL-8, C3a, and C4a concentrations became significantly higher in the ARDS group. Neither the ARDS nor non-ARDS patients showed the presence of circulating IL-1 beta, TNF-alpha, or endotoxin at any postinjury time point. CONCLUSIONS: These results demonstrate that measurements of plasma concentrations of proinflammatory cytokines, endotoxin, or complement fragments are not helpful in predicting the development of ARDS after severe accidental injury.

Adult↗
PubMed1994

Temporal patterns of hemodynamics, oxygen transport, cytokine activity, and complement activity in the development of adult respiratory distress syndrome after severe injury.

The aim of this study was to search for early inflammatory mediators in severely traumatized patients that could predict the occurrence of adult respiratory distress syndrome (ARDS). We measured sequential plasma levels of tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), complement fragment C3a, and endotoxin. In addition, we measured sequentially the values of hemodynamics, oxygen transport, and pulmonary function. The temporal patterns seen in the patients who developed ARDS were compared with those who did not. In the patients who developed ARDS, the first observed findings were low cardiac index (CI) and oxygen delivery (DO2) followed by progressive increases in IL-6, IL-8 and C3a levels, worsening of pulmonary function, and increases in hemodynamic values. The maximum values of IL-6, IL-8, and C3a occurred after the onset of ARDS. In the patients who did not develop ARDS, initial oxygen transport values were not low, the levels of IL-6, IL-8, and C3a decreased rapidly from their initial peaks, and there were no further increases in hemodynamic values. In both ARDS and nonARDS patients, no measurable quantities of TNF, IL-1, or endotoxin were found. We concluded that none of the mediators we measured reached their peaks before the onset of ARDS and none were found to be predictive of posttraumatic ARDS. However, these and other mediators may augment or intensify the development of ARDS.

Adult↗
PubMed1994

Elevated levels of soluble ICAM-1 correlate with the development of multiple organ failure in severely injured trauma patients.

Serum levels of interleukin-6, interleukin-8, the soluble receptor for tumor necrosis factor (sTNFr), and the soluble receptor for intercellular adhesion molecule-1 (sICAM-1) were measured serially in a series of 13 severely injured trauma patients to determine if any of these elements of the inflammatory response are predictive of multiple organ failure (MOF). Six of the 13 patients developed MOF as determined by a MOF scoring system. At the completion of resuscitation (when oxygen delivery and consumption were maximized) sICAM-1 levels were significantly higher in MOF patients before the development of clinical evidence of organ failure (700 +/- 67 ng/mL) compared with non-MOF patients (302 +/- 18 ng/mL). There was a significant correlation between the absolute level of sICAM-1 at the time of resuscitation and the severity of subsequent MOF. This finding suggests that leukocyte-endothelial cell interactions are upregulated immediately after injury and may be implicated in the end-organ injury that leads to MOF.

Adult↗