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Biomedical subjects

R W Sauerwein

Publications and source records attributed to R W Sauerwein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Posttranscriptional down-regulation of tumor necrosis factor-alpha and interleukin-1beta production in acute meningococcal infections.

The regulation of tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1beta) production was studied in patients with meningococcal disease. Circulating TNF and IL-1beta normalized within 1 day. TNF mRNA and IL-1beta mRNA in white blood cells decreased over 3-4 days. During the acute stage, TNF and IL-1beta production in stimulated whole blood cultures was down-regulated. After 4-5 days, this production was restored. The down-regulation was unlikely to be caused by circulating IL-6 and IL-10, as these cytokines normalized within 2-3 days. TNF mRNA in stimulated cultures during the acute stage, with down-regulated production, did not differ from that at recovery, with restored production. In contrast, the down-regulated production of IL-1beta was associated with significantly lower IL-1beta mRNA levels. Thus, TNF and IL-1beta production are differentially regulated. Whereas TNF production is regulated posttranscriptionally, IL-1beta production is also regulated at the mRNA level.

Anti-Bacterial Agents↗
PubMed1998

Malaria is associated with reduced serum retinol levels in rural Zambian children.

Vitamin A deficiency increases the risk of illness, while infections impair vitamin A status. Malaria is highly prevalent in rural Zambia. We describe the relationship between malaria and vitamin A status. We examined dietary vitamin A intake, malaria parasitaemia and serum concentrations of retinol, C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP) in 210 children under the age of 2. Vitamin A intake was low. Serum retinol was negatively correlated with malaria parasite count and to serum levels of CRP and AGP. Increased malaria parasite density resulted in raised CRP and AGP levels, which were negatively associated with serum retinol. We conclude that improvement of dietary vitamin A intake and prevention of infectious diseases, especially malaria, could alleviate vitamin A deficiency in this population.

Animals↗
PubMed1997

Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seropositive patients with Pneumocystis carinii pneumonia.

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.

AIDS-Related Opportunistic Infections↗
PubMed1997

Circulating tumour necrosis factor alpha is not involved in the development of cerebral malaria in Plasmodium berghei-infected C57Bl mice.

Administration of neutralizing anti-TNF alpha antibodies did not prevent Plasmodium berghei induced cerebral malaria (CM) in C57Bl/6 mice, when given at different dosages and time intervals. Elevated concentrations of immunoreactive TNF alpha were found in the circulation but no bioactive TNF alpha could be detected in mice developing CM. Furthermore, elevated TNF alpha receptor concentrations were measured in the plasma of mice developing CM. Plasma of these mice neutralized bioactive recombinant-mouse TNF alpha indicating that a part of the plasma TNF alpha-receptors were not complexed with TNF alpha. The apparent absence of free TNF alpha probably explains why treatment with antibodies against TNF alpha failed to prevent development of CM.

Animals↗
PubMed1997

Inflammatory mediators in children with protein-energy malnutrition.

Edema is a typical sign in kwashiorkor, which is present in a subset of patients with protein-energy-malnutrition (PEM). The pathophysiology of this edema is not well established. One of the abnormalities found in kwashiorkor is reduced concentrations of antioxidants, suggesting a compromised capacity to neutralize free radicals, which are known to induce tissue damage. We have studied plasma concentrations of several mediators of the inflammatory cascade. Concentrations of interleukin 6 (IL-6), C-reactive protein, and the soluble receptors of tumor necrosis factor alpha (sTNFR-p55 and sTNFR-p75) are greater in children with PEM, particularly in those with kwashiorkor, whereas soluble receptors of IL-6 (sIL6R-gp80) and IL-1 receptor antagonist concentrations are not significantly different from those of healthy children. In addition, concentrations of IL-6, sTNFR-p55, and sTNFR-p75 are greater in kwashiorkor patients irrespective of the presence of infection. Antioxidant status, as determined by plasma concentrations of glutathione and vitamin E, is significantly reduced in kwashiorkor patients. These data support the notion that children with edematous malnutrition show increased inflammatory reactivity that may contribute to edema formation.

Antioxidants↗
PubMed1997

Differential induction of pro- and anti-inflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment.

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.

Anti-Bacterial Agents↗
PubMed1997

Leukocytes in a Plasmodium falciparum-infected blood meal reduce transmission of malaria to Anopheles mosquitoes.

Mosquitoes are infected with Plasmodium falciparum by taking a blood meal from a gametocyte carrier. Since a mosquito takes a volume of 1 to 2 microl, a blood meal may contain 1 x 10(4) to 3 x 10(4) leukocytes (WBC). The majority of WBC are composed of neutrophils which may phagocytose and kill developing gametes inside the mosquito midgut. Phagocytosis was measured in vitro by a luminol-dependent chemiluminescence (CL) assay. In the presence of P. falciparum gametes, sera from areas of endemicity had an increased CL response compared to controls. In mosquito membrane feeding experiments some such sera showed a transmission reduction which was related to the presence of viable WBC. The results of this study suggest that phagocytosis of opsonized gametes inside the mosquito midgut occurs and can contribute to a reduction in the transmission of P. falciparum parasites.

Animals↗
PubMed1996

[Acanthamoeba keratitis].

Three patients, women aged 69, 25 and 30 years, with refractory keratitis were found to have a rare infection with Acanthamoeba. All wore soft contact lenses. The frequency of Acanthamoeba keratitis increased in recent years. At present, an efficacious antiprotozoal therapy is available, for instance in the form of polyhexamethylene biguanide and propamidine. In cases of refractory keratitis, the possibility of an Acanthamoeba infection should be taken into account.

Acanthamoeba Keratitis↗
PubMed1996

Pro-inflammatory cytokines in lung and blood during steroid-induced Pneumocystis carinii pneumonia in rats.

To gain more insight into the role of cytokines in Pneumocystis carinii pneumonia (PCP) we followed pro-inflammatory cytokine profiles in rats with steroid-induced PCP at 2-week intervals. The cytokines measured were immunoreactive interleukin-1beta (IL-1beta), bioactive interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). In vivo cytokine concentrations were determined in three compartments, i.e., bronchoalveolar lavage (BAL) fluid, lung homogenates, and plasma. Lipopolysaccharide (LPS) -stimulated cytokine production by alveolar cells and in whole-blood cultures was measured ex vivo. P carinii load and host inflammatory response, as determined by lung/body weight ratio and 111indium-IgG biodistribution were monitored throughout developing PCP. IL-1beta was elevated in lung homogenates (600, range <20-1260 pg/mL) and IL-6 in BAL fluid (48, range <20-115 pg/mL), whereas the pro-inflammatory cytokine concentrations were not increased in plasma. Thus in rats with PCP elevated pro-inflammatory cytokine concentrations were found to be restricted to the lung compartments. Corticosteroids did not significantly influence cytokine concentrations, but showed profound inhibitory effects on ex vivo cytokine production. The LPS-stimulated cytokine production by alveolar cells gradually decreased during the 6 weeks after the start of the steroid injections, whereas the production in whole blood cultures was immediately and completely suppressed.

Animals↗
PubMed1996

Interleukin-6 and its soluble receptor during acute meningococcal infections: effect of plasma or whole blood exchange.

OBJECTIVES: To determine the pattern of the soluble interleukin (IL)-6 receptor during acute meningococcal infections and recovery phase, and to measure the effect of plasma or whole blood exchange on the plasma concentrations of these mediators. DESIGN: Prospective, descriptive patient study. SETTING: University hospital intensive care unit. PATIENTS: Patients with bacteriologically proven meningococcal infections were entered in the study. Three group were formed: a) patients with meningitis without shock (group A); b) patients with meningitis and shock (group B); and c) patients with shock only (group C). INTERVENTIONS: Part (n = 9) of the patients with shock underwent plasma or whole blood exchange. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of interleukin-6 and soluble IL-6 receptors were determined sequentially during the acute and recovery phases. Peak concentrations of IL-6 were highest in group C, followed by group B and group A. Soluble IL-6 receptor concentrations showed an opposite pattern and were all below normal. Soluble IL-6 receptor concentrations were negatively correlated with the IL-6 concentrations. During recovery, IL-6 rapidly decreased and soluble IL-6 receptors increased to supranormal concentrations, after which concentrations returned to normal. Plasma or whole blood exchange did not significantly influence IL-6 concentrations but did increase the soluble IL-6 receptor concentration directly after an exchange session followed by a rapid decrease. CONCLUSIONS: Soluble IL-6 receptor concentrations are low in acute meningococcal infections. Plasma or whole blood exchange temporarily increases these concentrations. It needs to be determined whether the effect of this therapy is beneficial to the patient.

Acute Disease↗
PubMed1996

Encephalocytozoon intestinalis-specific monoclonal antibodies for laboratory diagnosis of microsporidiosis.

Two monoclonal antibodies which can be used for the unambiguous identification by fluorescence microscopy of Encephalitozoon intestinalis spores in clinical specimens are described. Monoclonal antibody Si91 is specific for the extruded polar filament, and Si13 recognizes the surfaces of E. intestinalis spores. No cross-reaction with spores of Encephalitozoon hellem was observed. Immunogold electron microscopy confirmed the specific reactivities of both antibodies. Combined in an indirect immunofluorescence assay, these antibodies are used to identify spores in feces. Although there was some cross-reaction with fecal bacteria and fungi, the typical morphology of the extruded polar filaments enabled proper identification of the E. intestinalis spores. Parasites could also be demonstrated to be present in urine, nasal swabs, lung brush biopsy specimens, and bronchoalveolar lavage fluid from a patient with disseminated infection with E. intestinalis. The use of these monoclonal antibodies facilitates the detection and species determination of E. intestinalis in clinical specimens.

AIDS-Related Opportunistic Infections↗
PubMed1995

Plasmodium falciparum: a comparison of the activity of Pfs230-specific antibodies in an assay of transmission-blocking immunity and specific competition ELISAs.

The activity of monoclonal antibodies (mAbs) that specifically recognize the Plasmodium falciparum sexual stage-specific protein Pfs230 was analyzed. All mAbs reacted with the surface of extracellular sexual forms of the parasite in a suspension immunofluorescence antibody reaction and precipitated the Pfs230 protein from an NP-40 extract of surface radioiodinated macrogametes/zygotes. Only mAb that bound complement blocked transmission, whereas mAb that did not bind complement but competed with the complement-binding mAb for binding to the same epitope did not block transmission. These mAbs were used to develop Pfs230-specific competition ELISAs to analyze epitope diversity and to analyze the binding characteristics of anti-Pfs230 antibodies in human serum. Transmission-blocking (TB) antibodies in test/field sera competed in the competition ELISA for binding with epitope-specific, labeled mAbs against Pfs230. At least five different epitope regions could be defined with the competition ELISAs. All 46 sera from gametocyte carriers immunoprecipitated the Pfs230 molecule, while 19 of these sera blocked transmission in the bioassay. Five of the transmission-blocking and one of the nonblocking sera competed with monoclonal antibodies. A method comparison analysis was used to determine agreement between reactions in a competitive ELISA and the TB activity examined in the bioassay. The index of agreement kappa between outcomes of the bioassay and ELISA was fair to poor (kappa = 0.25) but since its range includes values below 0 the relation between the data obtained by the bioassay and the competition ELISA can be explained by chance alone. The serological data did not reveal a correlation between immunoprecipitation of Pfs230 and TB activity.

Adolescent↗
PubMed1995

Circulating interleukin-6 receptor in patients with sepsis syndrome.

Concentrations of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), and soluble tumor necrosis factor receptor (sTNFR) p55 and p75 were measured in 25 patients with sepsis syndrome. Sequential blood samples were drawn from patients during a 7-h period. IL-6 concentrations were 34-763,000 pg/mL; they were higher in nonsurvivors than survivors, but the difference was not statistically significant. In septic patients, the median sIL-6R concentration was significantly lower than in 19 healthy volunteers (43 vs. 80 ng/mL). sIL-6R concentrations in survivors were not significantly different than those in nonsurvivors. There was a negative correlation between IL-6 and sIL-6R in septic patients (r = -.72). In patients with moderately impaired renal function, sIL-6R levels were not affected, but the concentrations of sTNFRs were significantly higher.

Adolescent↗
PubMed1995

Correlation between proinflammatory cytokines and antiinflammatory mediators and the severity of disease in meningococcal infections.

Pro- and antiinflammatory cytokines and mediators were measured in 39 patients with acute life-threatening meningococcal infections classified into 3 groups: A, meningitis without shock (n = 20); B, meningitis with shock (n = 9); and C, shock without meningitis (n = 10). The plasma concentrations of proinflammatory endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 and antiinflammatory cytokines and mediators IL-1 receptor antagonist, IL-10, and soluble TNF receptors p55 and p75 were strongly associated with this classification; the highest concentrations were in group C. IL-4 was not measurable. IL-1 beta was increased only in rapidly fatal cases. In addition, cerebrospinal fluid (CSF) was analyzed in 21 patients for TNF-alpha and its soluble receptors. In CSF, these compounds were mainly increased in group A, reflecting an intrathecal compartmentalized cytokine production. It is concluded that both pro- and antiinflammatory mediators are simultaneously increased and are strongly associated with a classification based on simple clinical parameters.

Adolescent↗
PubMed1995

Susceptibility to Plasmodium berghei infection in rats is modulated by the acute phase response.

Brown Norway (BN) and Sprague Dawley (SD) rats are known to differ in their susceptibility to infection with sporozoites of Plasmodium berghei, as measured by the density of liver schizonts. Because of the known inhibitory effect of non-specific immunomodulators on schizont development, we compared some aspects of the acute phase response in these two rat strains. LPS induced IL-6 production was measured in supernatants of spleen cells and peritoneal macrophages of both strains. SD rats, which are the least susceptible to P. berghei sporozoites, showed significantly higher IL-6 production by macrophages from both sources. When LPS was administered in vivo, SD rats also had a significantly higher IL-6 response. Hepatocytes from both strains were cultured in the presence of IL-6. After three days of culture, alpha 2-Macroglobulin concentrations in the supernatants of SD hepatocytes were much higher than those from BN rats. Kupffer cell depletion in both BN and SD rats was correlated with a significant increase in liver schizont density, but did not abrogate the difference in susceptibility. From these results we conclude that the higher cytokine production capacity of SD rats compared to BN rats, may contribute to the difference in susceptibility to P. berghei sporozoites between these strains, but that other yet unknown factors are also involved.

Acute-Phase Proteins↗
PubMed1995

Plasma cytokine levels in hemolytic uremic syndrome.

The cytokines tumor necrosis factor-alpha (TNF-alpha) and its soluble TNF receptors 55 and 75 (sTNFR55, sTNFR75), interleukin-1 beta (IL-1BETA) and interleukin-6 (IL-6) were measured in plasma from 13 patients with the hemolytic uremic syndrome (HUS) on admission. No significant changes in the plasma levels of TNF-alpha and IL-1beta were detected in the HUS patients as compared to the plasma levels of the control groups. Levels of IL-6 were significantly elevated in the plasma of those HUS patients who had external manifestations, consisting of seizures, loss of consciousness, coma and pancreatic necrosis. Although the exact function of IL-6 in the plasma of HUS patients is still unknown and the group of HUS patients is small, plasma IL-6 is associated with the the severity and outcome of the disease. Plasma levels of sTNR55 and sTNFR75 were significantly elevated in all HUS patients compared to the healthy controls, but they were also elevated in the children with chronic renal failure. This indicates that elevated levels of circulating sTNFR should be carefully interpreted when kidney failure exists.

Child↗
PubMed1995

Inhibition of Plasmodium berghei liver schizont development and reduction of cytokine production capacity in rats by dietary fish oil supplementation.

Experimental primary infection with Plasmodium berghei in rats is known to be influenced by several cytokines. Dietary supplementation of n-3 fatty acids has been shown to influence cytokine production capacity and to protect mice from cerebral malaria. We investigated the effect of dietary fish oil (FO) supplementation on cytokine and nitric oxide production and liver schizont development in male brown Norway rats. Control groups were fed either a corn oil-supplemented diet (CO) or standard lab chow (LC). After six weeks on either diet, rats given supplementary FO had a significantly lower production of interleukin-1 (IL-1) and IL-6 after stimulation with lipopolysaccharide, and also had significantly lower numbers of liver schizonts compared with CO- or LC-fed animals. We conclude that in rats, an FO-supplemented diet reduces the production capacity of IL-1 and IL-6 and inhibits schizont development after intravenous inoculation of P. berghei sporozoites. Fish oil did not influence nitric oxide production by peritoneal macrophages.

Animals↗