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Biomedical subjects

E Fischer

Publications and source records attributed to E Fischer.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effect of hyperglycaemia on the hepatic metabolism and excretion of xenobiotics.

The biliary excretion of drugs has been investigated in hyperglycaemic male Wistar rats. Hyperglycaemia was produced by a continuous infusion of glucose in different concentrations. To examine the effect of hyperglycaemia on the biliary excretion rate of xenobiotics, one representative of non-metabolizing exogenous organic anions (rose bengal) and metabolizing phenolic drugs (p-nitrophenol) as model compounds were used. A dose-dependent increase of blood and bile glucose level was found after the continuous infusion of glucose in a concentration of 10, 20 or 30%. Biliary flow and biliary excretion of rose bengal were significantly depressed in hyperglycaemic rats. Hepatic conjugation of p-nitrophenol with glucuronic acid appeared to be decreased, however, a compensatory increase of sulphoconjugation of p-nitrophenol was observed in hyperglycaemic rats. Biliary excretion of unconjugated p-nitrophenol was negatively influenced by high blood glucose level and the overall hepatic elimination of p-nitrophenol was also diminished by hyperglycaemia. Insulin (I U/kg i.v.) compensated partly the depressive effect of high blood sugar level on the biliary excretion rate of rose bengal, however, it was unable to abolish completely the negative effects of hyperglycaemia. These results indicate that hyperglycaemia does alter the hepatic elimination of xenobiotics.

Animals↗
PubMed1994

CR1(CD35) and CR2(CD21) complement C3 receptors are expressed on normal human thymocytes and mediate infection of thymocytes with opsonized human immunodeficiency virus.

The present study demonstrates that the C3b receptor CR1 (CD35) and the C3dg/Epstein-Barr virus receptor CR2 (CD21) are expressed by 25% and 70% of normal human thymocytes, respectively. The expression of CR2 extends to both CD1+ and CD1- cells in the thymus. Two subsets of CR2+ thymocytes were defined expressing low and high density of the receptor. The CR2++ subset represented 20% of CR2+ thymocytes and co-expressed the CR1 receptor. CR2++ thymocytes expressed an immature CD1dull, CD3-, CD4dull, CD8-, CD7++ phenotype and included a subpopulation of large cells expressing CD34. Twenty percent of thymocytes expressed the CD21 epitope defined by monoclonal antibody BU32, which is involved in the binding of CD23 to CD21. These observations provide a basis for a role for CD21 in the proliferation and differentiation of thymocytes at early stages of maturation. The functionality of CR1 and CR2 on thymocytes was evidenced by the ability of the receptors to mediate infection of cells with complement-opsonized human immunodeficiency virus (HIV). The results may be relevant to the immunopathogenesis of HIV infection.

Child↗
PubMed1994

A lectin from the Asian horseshoe crab Tachypleus tridentatus: purification, specificity and interaction with tumour cells.

A lectin from the haemolymph of the Asian horseshoe crab Tachypleus tridentatus was purified to homogeneity by affinity chromatography on Sepharose 4B-bound N-acetylneuraminic acid. The specificity of this lectin was studied by haemagglutination inhibition with sialic acid analogues, N-acetylhexosamines and glycoproteins. For the interaction with the agglutinin the N-acetyl group and the glyceryl side chain of N-acetylneuraminic acid are important, while presence of an aglycon, specially an alpha-glycosidically linked lactose increases affinity to the lectin. The strongest glycoprotein inhibitors were ovine as well as bovine submaxillary mucin and Collocalia mucin, all being O-chain glycoproteins but carrying completely different carbohydrate chains. The majority of N-chain proteins were inactive. As the lectin agglutinates human erythrocytes, but not the murine lymphoma lines Eb and ESb or the human colon carcinoma HT 29, these cancer cells apparently lack the 'Tachypleus tridentatus agglutinin-receptor' which is present on red cells and O-chain glycoproteins.

Amino Sugars↗
PubMed1994

Inhibition of complement activation by natural sulfated polysaccharides (fucans) from brown seaweed.

In the present study, we demonstrate that natural sulfated polysaccharides (fucans) isolated from brown seaweed are potent inhibitors of human complement activation. A fucan fraction of chromatographic molecular weight 22,600, termed BS8, was found to inhibit classical and alternative pathway activation in whole serum in a dose-dependent fashion. Fucan BS8 inhibited formation of the classical pathway C3 convertase by interfering with C1 activation or by inhibiting C4 cleavage and the interaction between C4b and C2. The fucan also inhibited formation/function of the alternative pathway C3 convertase by suppressing the binding of B to C3b and by interfering with the stabilizing function of Properdin. The inhibitory effect of fucans on formation of the C3 convertases was dependent on the molecular weight of the polysaccharide for compounds of chromatographic molecular weight below 16,600. Fucan had no effect on the function of the terminal complex. Since fucans were more efficient than heparin in inhibiting activation of the classical pathway in whole serum and exhibited a lesser specific anticoagulant activity on a molar basis, our results suggest that these natural sulfated polysaccharides have a potential for use as anti-complementary and anti-inflammatory agents.

Complement Activation↗
PubMed1994

Traditional Preperitoneal Approach to Inguinal Hernias.

The preperitoneal approach desirably and advantageously permits direct exposure to transversalis fascia without disturbing the inguinal canal structures and allows restoration of the integrity of this layer in a anatomical, tension-free, and sutureless manner. The essential feature of prosthetic versus nonprosthetic repair of inguinofermoral hernias is the replacement of the transversalis fascia by a large mesh that extends far beyond the borders of myopectineal orifice unnecessary. Therefore, the indications for preperitoneal prosthetic repair include all recurrent and multiply recurrent groin hernias, and bilateral hernias in older patients.

Journal Article↗
PubMed1994

A prospective comparison of two multiple organ dysfunction/failure scoring systems for prediction of mortality in critical surgical illness.

Multiple organ failure (MOF) is the primary cause of death in surgical intensive care units (SICU). Mortality increases with an increasing number of failed organs, but it has been recognized that lesser degrees of organ dysfunction occur commonly. Such gradations of the multiple organ dysfunction syndrome (MODS) are postulated to provide more descriptive and predictive power. We analyzed and compared two different MODS/MOF scoring systems and determined the utility of gradations of organ dysfunction for prediction of mortality in MODS/MOF. One of the scoring systems defines organ failure as an all-or-nothing phenomenon for each organ, whereas the other scoring system describes increasing organ dysfunction on a 24-point scale. Each scoring system assesses the same six organs. Admission APACHE II (AII) and AIII scores were calculated as independent estimates of mortality. In 867 consecutive SICU admissions, 261 patients (30%) had some degree of organ dysfunction, of whom 142 patients (54%) met criteria for single or multiple organ failure. The mean admission AII score was 19 (25 for nonsurvivors), and the AIII score was 62 (91 for nonsurvivors). Overall mortality was 5.8%, but among those patients with organ dysfunction, mortality was 19%. Death was equally likely for comparable degrees of organ dysfunction and failure. Mortality increased (p < 0.01, ANOVA) with higher scores in both systems. In patients with 9-12 organ dysfunction points, the number of failed organs was 1.5 +/- 0.2 in 34 survivors, versus 2.9 +/- 0.3 in the 14 nonsurvivors (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

APACHE↗
PubMed1994

Alcohol and drug disorders among physically abusive and neglectful parents in a community-based sample.

OBJECTIVES: The purpose of this study was to compare the frequency of substance use disorders and symptoms between adults reporting child physical abuse or neglect and individually matched control subjects in a community sample. METHODS: In a nested case-control study, 169 adults reporting physical abuse of a child and 209 adults reporting neglect of a child from 11,662 individuals successfully interviewed in a probabilistic survey in four communities were individually matched with control subjects drawn from the participants. Case subjects were compared with control subjects on the number of alcohol- or drug-related symptoms and disorder diagnoses as determined by symptoms from the Diagnostic Interview Schedule. RESULTS: Respondents reporting either physical abuse or neglect of children were much more likely than their matched control subjects to report substance abuse or dependence. These differences persisted after potential confounding variables were controlled for. CONCLUSIONS: Parental substance abuse and dependence, independent of confounding factors, are highly associated with child maltreatment. Inconsistent results in previous studies may have arisen from reliance on referred samples and unstandardized assessment methods. Agencies involved in the care of abused or neglected children and their families should consider incorporating routine substance abuse evaluations with treatment, or referral for treatment, where indicated.

Adult↗
PubMed1994

Effects of acid-base correction on hemodynamics, oxygen dynamics, and resuscitability in severe canine hemorrhagic shock.

OBJECTIVE: To compare the effects of hypertonic saline, sodium bicarbonate, and Carbicarb resuscitation on acid-base balance, hemodynamics, and oxygen dynamics in a reperfused, canine hemorrhagic shock model. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-five anesthetized, mongrel dogs. INTERVENTIONS: After the administration of anesthesia, the dogs were intubated and mechanically ventilated. Vascular catheters were inserted into each femoral artery, for continuous blood pressure monitoring, intermittent blood sampling, and for establishing controlled hemorrhage. A pulmonary artery catheter was inserted via the right jugular vein. Inhaled and exhaled gases were continuously analyzed using a metabolic gas monitor. The animals were subjected to 90 mins of controlled hemorrhagic shock. They were then randomly given a 2.5-mL/kg equimolar injection of 8.4% sodium bicarbonate, Carbicarb, or 5.84% hypertonic saline. The sodium load per kilogram of body weight was identical in all three groups. Thirty minutes later, the animals were retransfused with the shed blood over 15 mins and further observed for 120 mins. MEASUREMENTS AND MAIN RESULTS: Carbicarb and sodium bicarbonate both significantly increased bicarbonate concentrations compared with saline. Arterial and venous blood pH increased more with Carbicarb than with bicarbonate but this increase was not statistically significant. After shock but before retransfusion, all three treatments moderately increased blood pressure, cardiac index, oxygen delivery index, and oxygen consumption index to a similar extent. After retransfusion, blood pressure, cardiac index, and oxygen dynamics temporarily improved in all groups, without significant improvement in the bicarbonate and Carbicarb-treated animals, despite their excellent acid-base status. CONCLUSIONS: In severe canine hemorrhagic shock, Carbicarb, bicarbonate, and hypertonic saline appear to possess similar hemodynamic properties despite the buffering properties of bicarbonate and Carbicarb. The similar responses may be due to their identical sodium content. Arterial pH correction does not appear to further improve the responses to blood retransfusion.

Acid-Base Imbalance↗
PubMed1993

Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man.

Previous experimental data have demonstrated that steroid pretreatment regulates endotoxin-elicited cytokine production. The timing of such hypercortisolemia also appears to be a major determinant of both the systemic and the cytokine response to infectious stimuli. Our study was undertaken to further study the in vivo influence of glucocorticoid infusion concurrent with and before endotoxin exposure in man. A total of 23 normal human subjects were given endotoxin (LPS) alone or pretreated with hydrocortisone infusion for 6 h immediately before and concomitant to LPS administration; or rendered hypercortisolemic for a 6-h period waiting 6, 12, or 144 h before LPS administration. LPS administration was followed by significant elevations in temperature (1.9 +/- 0.3 degrees C), pulse (29 +/- 6 bpm), and resting energy expenditure (26.2 +/- 0.4 kcal/kg/day) as well as epinephrine (236 +/- 59 pg/ml), cortisol (296 +/- 29), and C-reactive protein (4.2 +/- .03 mg/dl) as compared with base-line values. Levels of TNF and IL-6 that were not detectable before LPS administration, peaked, respectively, at 90 and 120 min after LPS (155 +/- 4 pg/ml, 12 +/- 1 U/ml). Glucocorticoids when given immediately before and concomitant with LPS significantly attenuated the temperature (0.8 +/- 0.01 degrees C) and pulse rate response (10 +/- 3 bpm) seen after LPS alone as well as suppressing peak levels of epinephrine (78 +/- 14 pg/ml) and C-reactive protein (undetected). TNF remained undetectable in this group although the IL-6 response (14 +/- 1 U/ml) was unchanged. With a 6-h interval between hydrocortisone infusion and LPS challenge, changes in temperature, pulse, resting energy expenditure, and hormone levels were similar to those seen after LPS alone whereas TNF remained undetectable and IL-6 levels were similar to subjects receiving LPS alone. Subjects receiving LPS after 12 or 144 h after hydrocortisone infusion displayed hemodynamic and hormonal responses similar to the LPS alone group, yet mounted significantly greater circulating levels of both IL-6 (117 +/- 14 U/ml, 160 +/- 51 U/ml at 12 and 144 h) and TNF (609 +/- 173, 671 +/- 132 pg/ml at 12 and 144 h) to those observed after LPS alone. We conclude that antecedent periods of hypercortisolemia participate in regulation of the hemodynamic, hormonal, and cytokine responses to endotoxin and that a complex temporal relationship between hypercortisolemia and LPS induced cytokine and systemic responses exists.

Adult↗
PubMed1993

Comparison of peripheral blood leukocyte kinetics after live Escherichia coli, endotoxin, or interleukin-1 alpha administration. Studies using a novel interleukin-1 receptor antagonist.

OBJECTIVE: This study was undertaken to evaluate whether hematologic and immunologic effects observed after bacteremia and endotoxemia in the host could be replicated by administration of recombinant human interleukin-1 alpha (IL-1 alpha) in a primate model. Furthermore, to determine whether endogenously produced interleukin-1 (IL-1) contributes to the changes observed during endotoxemia or gram-negative septic shock, a specific IL-1 receptor antagonist (IL-1 ra) was administered. SUMMARY BACKGROUND DATA: The lipopolysaccharide (LPS) component of the outer membrane of gram-negative bacteria initiates a constellation of metabolic and immunologic host responses. IL-1, a macrophage-derived cytokine, acts as a key mediator in the host response to infection and inflammation. METHODS: Baboons were randomly assigned to receive either recombinant human IL-1 alpha, LPS, or live Escherichia coli both with or without concomitant administration of IL-1ra. Blood was collected hourly and analyzed using flow cytometric techniques. RESULTS: Both endotoxemia and live E. coli bacteremia induced an acute granulocytopenia; however, the granulocytopenia gradually resolved in the endotoxemic group, but was sustained in the bacteremic group. An early lymphopenia and monocytopenia was elicited by LPS or E. coli and persisted throughout the experiment. Recombinant human IL-1 alpha induced the following: (1) an early, transient decline in granulocytes followed by a sustained granulocytosis; (2) a lymphopenia; and (3) a transient monocytopenia followed by a gradual return to baseline. Although IL-1ra had no effect on leukocyte kinetics with either live E. coli or LPS, the IL-1ra significantly abrogated the monocytopenia seen with recombinant human IL-1 alpha administration alone. CONCLUSIONS: These results suggest that administration of recombinant human IL-1 alpha can replicate some of the characteristic patterns of hematologic change associated with bacteremia and endotoxemia. However, an endogenous IL-1 response is not required for these changes to occur. Rather, the data suggest that other inflammatory mediators induced by endotoxemia or gram-negative bacteremia, such as tumor necrosis factor-alpha (TNF alpha), may be involved.

Animals↗
PubMed1993

Evidence for the role of CR1 (CD35), in addition to CR2 (CD21), in facilitating infection of human T cells with opsonized HIV.

Complement activation by HIV results in the binding of C3 fragments to the gp160 complex and enhanced infection of C3 receptor-bearing target cells. We have studied complement-mediated enhancement of infection of the human CD4-positive T-cell line HPB-ALL which expresses the CR1 (CD35) and CR2 (CD21) receptors for C3. CR1 and CR2 are present on 15% and 40% of normal peripheral blood CD4-positive T lymphocytes respectively. Opsonization of the virus with complement resulted in a 3- to 10-fold enhancement of infection of HPB-ALL cells, as assessed by measuring the release of p24 antigen in culture supernatants throughout the culture period. Blockade of CR2 with cross-linked anti-CR2 monoclonal antibodies decreased infection to the level observed with unopsonized virus. Blocking CR1 reduced complement-mediated infection by 50-80%. Experiments using serum deficient in complement factor I demonstrated that CR1 mediates the interaction between opsonized virus and T cells in addition to its ability to serve as a cofactor for the cleavage of C3b into smaller fragments that interact with CR2. A requirement for CD4 in complement-mediated enhancement of infection was observed with HIV-1 Bru but not with HIV-1 RF. Thus, CR1 and CR2 contribute in an independent and complementary fashion to penetration of opsonized virus into complement receptor-expressing T cells. Involvement of CD4 in infection with opsonized virus depends on the viral strain.

CD4 Antigens↗
PubMed1993

Dentifrice abrasiveness on microfill composite resin and dentin: a comparative study.

This in vitro study evaluated the abrasiveness of seven dentifrices on microfill composite resin discs and dentin surfaces. The composite resin discs and dentin surfaces were brushed in groups using slurries of the different dentifrices. Each specimen was subjected to 2400 strokes using medium bristle toothbrushes at a brush tension of 150 g. Any changes in surface roughness were noted through the use of a mechanical profiler or profileometer and scanning electron micrographs. The results of this study have indicated that Rembrandt Whitening Toothpaste was significantly less abrasive to the microfill composite discs and dentin surfaces compared to the other dentifrices tested (p < .05, ANOVA). Further clinical studies may be warranted to test the abrasiveness of dentifrices, especially if they are used over extended periods of time.

Analysis of Variance↗
PubMed1992

Expression, molecular association, and functions of C3 complement receptors CR1 (CD35) and CR2 (CD21) on the human T cell line HPB-ALL.

We have investigated the expression, molecular association, ligand binding properties, and ability to transduce intracellular signals of CR1 and CR2 C3 receptors on cells of the human HPB-ALL T cell line. CR1 and CR2 on HPB-ALL cells bound polymeric C3b and C3dg and several anti-CR1 and anti-CR2 mAb recognizing different epitopes of the receptors on normal peripheral blood cells. Immunoprecipitated CR1 and CR2 exhibited similar m.w. to those of the receptors on normal peripheral blood T and B lymphocytes. CR1 and CR2 were partially associated in the form of CR1/CR2 complexes in the cell membrane as assessed by the ability of the receptors to cocap and cointernalize and to form a detergent-sensitive complex upon immunoprecipitation analysis. Triggering of CR2 with mAb OKB7 that recognizes an epitope associated with the ligand binding site of the receptor induced an increase in intracellular free calcium concentration in HPB-ALL cells. The signal provided by mAb OKB7 did not synergize with that triggered by anti-CD3 mAb UCHT1. Triggering of CR1 did not result in changes in intracellular free calcium concentration. Our observations have significance for the biology of normal human T cells because the majority of peripheral blood T cells that express CR1 also expressed CR2 and because a change in (Ca2+)i was induced by mAb OKB7 in purified normal T cells. These functions may be relevant for the regulatory role of C3 fragments on the immune response to T-dependent Ag and for the penetration into T cells of lymphocytotropic viruses.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1992

Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo.

Tumor necrosis factor alpha (TNF alpha), a primary mediator of systemic responses to sepsis and infection, can be injurious to the organism when present in excessive quantities. Here we report that two types of naturally occurring soluble TNF receptors (sTNFR-I and sTNFR-II) circulate in human experimental endotoxemia and in critically ill patients and demonstrate that they neutralize TNF alpha-induced cytotoxicity and immunoreactivity in vitro. Utilizing immunoassays that discriminate between total sTNFR-I and sTNFR-I not bound to TNF alpha, we show that sTNFR-I-TNF alpha complexes may circulate even in the absence of detectable free TNF alpha. To investigate the therapeutic possibilities of sTNFR-I, recombinant protein was administered to nonhuman primates with lethal bacteremia and found to attenuate hemodynamic collapse and cytokine induction. We conclude that soluble receptors for TNF alpha are inducible in inflammation and circulate at levels sufficient to block the in vitro cytotoxicity associated with TNF alpha levels observed in nonlethal infection. Administration of sTNFR-I can prevent the adverse pathologic sequelae caused by the exaggerated TNF alpha production observed in lethal sepsis.

Animals↗
PubMed1992

Specificity of the sialic acid-binding lectin from the snail Cepaea hortensis.

The specificity of the sialic acid-binding lectin from the snail Cepaea hortensis, purified by affinity chromatography on fetuin-Sepharose, was studied by hemagglutination inhibition assay applying 32 sialic acid derivatives and 14 glycoproteins. 2-alpha-Methyl-9-O-acetyl-NeuAc was the most potent inhibitor, followed closely by 2-alpha-methyl-NeuAc and 2-alpha-benzyl-NeuAc. An axially orientated carboxyl group is a prerequisite for maximal lectin-sugar binding. Neither size nor polarity of the alpha-anomeric substituent significantly influenced inhibition potency. An intact sialic acid N-acetyl group is essential for optimal lectin-sugar interaction. The trihydroxypropyl side chain also is of great importance. However, a bulky hydrophobic substituent at the side chain like a 9-O-tosyl residue did not decrease binding to the lectin. The lectin did not distinguish between NeuAc alpha 2----3Gal beta 1----4Glc and NeuAc alpha 2----6Gal beta 1----4Glc. Among other sugars tested, only N-acetylglucosamine showed inhibition, although 50-fold less. The most potent glycoprotein inhibitors were those carrying O-chains only or preferentially, as ovine submaxillary mucin, bovine submaxillary mucin, and glycophorin A. Tamm-Horsfall protein was an exception being a strong inhibitor, although carrying only N-chains. Asialoglycoproteins were inactive. Glycoproteins containing the NeuAc alpha 2----3Gal sequence inhibited the lectin as well as those with NeuAc alpha 2----6GalNAc. From the results a model of the lectin's binding site for sialic acid is suggested.

Animals↗
PubMed1992

Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease.

Interleukin-1 receptor antagonist (IL-1ra) is a 22-Kd protein that shares homology with IL-1 beta, binds to the IL-1 receptor, but has no known agonist properties. This inhibitor appears to be the first cytokine whose sole function is to block the actions of another cytokine. Exogenous IL-1ra administration has been shown to reduce mortality in experimental septic shock. We now report that IL-1ra is endogenously produced and circulates in experimental inflammation and in clinical disease. After experimental endotoxemia in human volunteers, IL-1ra concentrations increase from a baseline concentration of 460 +/- 200 pg mL-1 to 14,870 +/- 290 pg mL-1 at 3 hours (P less than .05). IL-1ra is also detectable in all plasma samples from critically ill patients with a mean concentration of 8,680 +/- 2,060 pg mL-1 (range 320 to 55,370 pgs mL-1). In nonhuman primates, Escherichia coli septic shock induces elevated plasma levels of IL-4ra (P less than .05). However, in animals that eventually succumb to septic shock, Il-1ra appears in quantities presumed inadequate to block the pathologic sequelae associated with high IL-1 beta levels. The findings suggest that IL-1ra may play a role in modulating the systemic host responses to a variety of nonlethal disease states by altering the balance between cytokines and their antagonists.

Adult↗