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Biomedical subjects

G Enders

Publications and source records attributed to G Enders.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pattern of adhesion molecule expression on vascular endothelium in Helicobacter pylori-associated antral gastritis.

BACKGROUND & AIMS: The inflammatory response in Helicobacter pylori-associated gastritis (HAG) is characterized by an intense infiltrate of granulocytes and lymphocytes. The emigration of white blood cells into sites of inflammation is mediated by receptors on endothelial cells and on blood leukocytes. The aim of this study was to characterize endothelial adhesion molecule expression in HAG leading to leukocyte infiltration. METHODS: Endothelially expressed adhesion molecules were studied in situ by immunohistochemical analysis of antral mucosal biopsy specimens from 20 control patients, 10 of whom had chemical gastritis, 10 normal mucosa, and 44 HAG. Adjacent biopsies were used to evaluate messenger RNA (mRNA) transcripts for the respective adhesion molecule and its inducing cytokines. RESULTS: Constitutive expression of P-selectin was found in all groups. Intercellular adhesion molecule 1 (ICAM-1) was up-regulated in patients with HAG and chemical gastritis in contrast to normal controls. Vascular adhesion molecule 1 (VCAM-1) was only found within lymphoid aggregates present in HAG. Neither mRNA transcripts nor the protein product of E-selectin were detected in normal or inflamed mucosa, although mRNA of the E-selectin-inducing cytokines, tumor necrosis factor alpha and interleukin 1beta, were found. CONCLUSIONS: Data suggest a major role of ICAM-1 and VCAM-1 in leukocyte-endothelial interaction in HAG without E-selectin up-regulation showing a unique pattern within the gastrointestinal tract, in contrast to observations made in inflammatory bowel disease.

Adult↗
PubMed1997

Diagnostic value of CD45RO expression on circulating T lymphocytes of fetuses and newborn infants with pre-, peri- or early post-natal infections.

We examined the expression of the CD45RO antigen, which characterizes the antigen primed/memory phenotype of T lymphocytes, as a marker for congenital infection in blood samples of newborns and fetuses. CD45RO expression on T cells was determined by triple-colour fluorescence flow cytometry. In total 537 blood samples of newborns and infants up to an age of 3 months and 89 fetal blood samples from gestational weeks 19-31 were analysed. Of the newborns and infants, 74 had a clinically, serologically and/or antigenically evident infection, and four of the fetuses had a confirmed intra-uterine infection. In 35 infants with acute predominantly bacterial infections such as sepsis or pneumonia, 17 (48.6%) had elevated CD45RO(bright) expression. In 39 infants with proven pre-, peri- or early post-natal infections with toxoplasmosis, cytomegalovirus (CMV), rubella, herpes simplex virus (HSV) or human herpes virus type 6 (HHV6), 25 (64.1%) exhibited enhanced CD45RO(bright) expression. Three of four fetuses with confirmed intra-uterine infection (three with CMV, one with parvovirus B19) exhibited elevated CD45RO(bright) expression. The specificity of the CD45RO assay for detecting microbial infections was 94.6% for newborns and infants up to 3 months and 90.6% for fetuses. It is concluded that elevated numbers of CD45RO(bright) T cells in infants up to 3 months of age strongly suggest an infection. However, the sensitivity of the CD45RO assay is not sufficient to enable the test to be used as a general marker for prescreening infants to detect pre-, peri- or early post-natally acquired infections.

Bacterial Infections↗
PubMed1997

Role of adherence in interleukin-8 induction in Helicobacter pylori-associated gastritis.

Active Helicobacter pylori-associated gastritis is characterized by a dense mucosal infiltration with granulocytes. Since H. pylori is noninvasive, secondary signals must induce the accumulation of granulocytes. Interleukin-8 (IL-8) has been shown to play a key role in this event. Using competitive reverse transcriptase-PCR on mRNA from gastric biopsies, we could show a clear correlation between the amount of IL-8 transcripts and the activity of H. pylori gastritis. Due to the inability of the bacterium to invade host cells, the epithelial layer is a potential candidate as an IL-8 source. To study the mechanism of IL-8 induction, established gastric carcinoma epithelial cell lines (AGS and Kato III) and well-defined H. pylori strains were used in a modified in vitro system. The experimental design enabled us to prevent direct contact of bacteria with epithelial cells by use of a filter membrane which did not block secreted bacterial products crossing the membrane. The data clearly showed that the direct contact of the bacterial cell with the epithelial cell is necessary for optimal IL-8 production because not only live bacteria, but also metabolically inactive bacteria, increased IL-8 secretion. Neither purified lipopolysaccharide nor water-soluble protein fractions of H. pylori NCTC 11637 and Tx30a nor the cytotoxin of H. pylori was able to increase IL-8 production significantly by the epithelial cells used. Furthermore, preparations of total membrane and outer membrane proteins of H. pylori were not able to stimulate IL-8 release in vitro. Accumulatively, these results imply that active metabolism is not necessary for stimulation as long as there is an intact membrane aiding the presentation of a stimulating membrane complex or aggregate on the surface of the bacteria. From these results, we conclude that whole bacteria and their direct contact with epithelial cells may be critical for IL-8 induction in vivo.

Bacterial Adhesion↗
PubMed1997

Evaluation of a new enzyme immunoassay based on recombinant Rubella virus-like particles for detection of immunoglobulin M antibodies to Rubella virus.

A new enzyme immunoassay for the detection of specific antibodies to rubella virus was evaluated at two different sites. This assay, the Roche Cobas Core Rubella IgM EIA recomb, uses a recombinant rubella virus-like particle and is based upon the immunoglobulin M (IgM) capture principle. It was compared to the Abbott IMx Rubella IgM test and to the Sorin ETI-RUBEK-M reverse test. The relative clinical specificities were 99.30% for the Roche test, 98.26% for the Abbott test, and 100% for the Sorin test. The relative clinical sensitivities were 100, 93.87, and 82.65%, respectively. In the case of most primary infections, IgM antibodies could be detected immediately at the onset of the disease and for up to 7 weeks. In the case of vaccinations, they could be detected between 3 and 12 weeks after vaccination.

Acute Disease↗
PubMed1997

Expression of inducible nitric oxide synthase and formation of nitric oxide by alveolar macrophages: an interspecies comparison.

Nitric oxide (NO) is suggested to play a role in mediating pulmonary injury. However, interspecies differences appear to exist in the ability of alveolar macrophages (AM) to express the inducible nitric oxide synthase (iNOS) and to generate NO. The purpose of this study was to compare iNOS expression and NO production by rat, hamster, monkey, and human AM using the identical experimental conditions in vitro. As AM donors, CD rats, Syrian golden hamsters, cynomolgus monkeys, and nonsmoking, healthy human volunteers were used. The AM were obtained by bronchoalveolar lavage and stimulated in vitro with various concentrations and combinations of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). The oxidation product of NO, nitrite, was measured in the AM supernatant by the Griess reaction. The expression of iNOS in AM was detected using immunocytochemistry and immunoblotting. The expression of iNOS mRNA was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rat AM, stimulated with either LPS or IFN-gamma, produced nitrite in a time- and dose-dependent manner. Combination of LPS and IFN-gamma resulted in a significantly enhanced nitrite formation. However, none of the treatments was able to induce hamster, monkey, or human AM to release measurable amounts of nitrite. Whereas expression of iNOS protein was only detected in stimulated rat AM, expression of iNOS mRNA was found in unstimulated and stimulated rat AM, slightly in stimulated hamster AM, but not in monkey and human AM. In conclusion, our findings point to distinct regulatory mechanisms of the NO pathway in AM from these four different species.

Adult↗
PubMed1997

Maternal serum alpha-fetoprotein and human chorionic gonadotropin in pregnant women with acute parvovirus B19 infection with and without fetal complications.

Maternal serum alpha-fetoprotein (MS-AFP) and human gonadotropin (MS-hCG) were retrospectively determined in 137 sera from 65 pregnant women with an acute parvovirus B19 infection. In 35 of the pregnant women, fetal complications occurred (group 1); in the remaining 30 women, there were no fetal complications (group 2). In group I, significant elevations of MS-AFP were detected in 13 of the 35 women (37 per cent) and of MS-hCG in 25 of the 35 women (71 per cent). In nine of those women, sera were obtained before occurrence of fetal complications and MS-AFP was elevated in one case and MS-hCG in four cases. In one woman, both MS-AFP and MS-hCG were elevated. In group 2, significant elevations of MS-AFP were found in two of the 30 women (6-7 per cent) and of MS-hCG in five of the 30 women (16.7 per cent). Neither MS-AFP nor MS-hCG appears to be a regular early marker for poor pregnancy outcome in parvovirus B19-infected pregnancies, although they were frequently elevated at the time of complications.

Acute Disease↗
PubMed1996

Granulocyte activation by Helicobacter pylori.

Helicobacter pylori-associated gastritis (HAG) is characterized by granulocytic and mononuclear cell infiltrates within infected gastric mucosa. Since the bacterium does not invade the epithelial layer, it must be assumed that components or products of the pathogen which permeate the epithelial barrier may initiate chemotaxis and activation of neutrophils. The aim of this study was to evaluate the effect of H. pylori water soluble protein (WSP) components on the induction of granulocyte adherence and activation. The results show that H. pylori WSP led to enhanced expression of the beta 2-integrin CD11b/CD18 on the granulocyte surface. Following upregulation of this adhesion molecule, activated granulocytes demonstrated increased adhesion to human endothelial cells (HUVEC) in culture. These observations support the hypothesis that in vivo neutrophil activation may be a direct result of H. pylori constituents promoting transendothelial migration into the lamina propria of infected gastric mucosa.

Bacterial Proteins↗
PubMed1996

IgM-specific serodiagnosis of acute human cytomegalovirus infection using recombinant autologous fusion proteins.

Portions of three human cytomegalovirus (HCMV) polypeptides, which were shown previously to be highly reactive with patient sera, were expressed in Escherichia coli as autologous fusion proteins. Purified recombinant polypeptides were used as antigens in enzyme linked immunosorbent assay (ELISA) and compared against assays which use natural viral antigen from cell culture for their ability to improve IgM-specific serology of acute HCMV-infection. A fusion protein (CM2) which contained two copies of the C-terminal portion of pUL44 (p52, aa 297-433) and one copy of a highly reactive fragment of the major DNA-binding protein pUL57 (aa 545-601) proved to be superior in sensitivity and specificity compared to assays which use culture derived antigen. A construct expressing one copy of the fragments from pUL44 and pUL57 in fusion with the 54 amino terminal residues of pUL32 (pp150, aa 994-1048) did not lead to an improved sensitivity compared to CM2. Adversely, this polypeptide reacted with a number of sera from asymptomatic blood donors infected latently with HCMV indicating low specificity of this antigen for the detection of acute infection. Concordant results were obtained with an antigen that combined only the C-terminal portions of pUL44 and pUL32 (CM3). ELISA experiments with sequential sera from renal transplant recipients demonstrated that detection of IgM-antibodies using CM2 as antigen correlated closely with acute infection, whereas high levels of IgM-antibodies against CM1 and CM3 persisted for a month following acute HCMV-infection. These results indicate that the application of a single autologous fusion protein like CM2 as antigen for recombinant ELISAs can improve significantly IgM-serodiagnosis of acute HCMV infection.

Antibodies, Viral↗
PubMed1996

Characterization of lymphocytic infiltrates in Helicobacter pylori-associated gastritis.

BACKGROUND: This study evaluated the specific subset composition of lymphocytes present in Helicobacter pylori-associated gastritis (HAG), since reports so far have led to inconclusive and conflicting results. METHODS: Endoscopic biopsy specimens from 56 patients were studied by quantitative immunohistochemistry using monoclonal antibodies against the lymphocyte markers CD3, CD22, CD4, CD8, CD45RO, CD1O3, TCR alpha/beta, and TCR gamma/delta. Lamina propria and intraepithelial compartments were evaluated separately. Grade, activity, and density of bacterial colonisation were assessed histologically and with Warthin-Starry stain. RESULTS: Evaluation showed a significant increase in CD4+, CD45RO+, TCR alpha/beta+ activated lamina propria lymphocytes in HAG which correlated with grade and activity of gastritis and degree of bacterial colonisation, whereas subsets of intraepithelial lymphocytes did not change significantly. TCR gamma/delta+ T cells were not found to be increased in HAG. CONCLUSIONS: Selective expansion of CD4+, CD45RO+ memory-type T cells could reflect an antigen-specific and/or chemokine-mediated effect in HAG. Locally produced CC chemokines such as RANTES have been detected in HAG.

Adult↗
PubMed1995

The pRB-related protein p107 contains two growth suppression domains: independent interactions with E2F and cyclin/cdk complexes.

Unregulated expression of either the retinoblastoma protein (pRB) or the related protein p107 can cause growth arrest of sensitive cells in the G1 phase of the cell cycle. However, growth arrests mediated by p107 and pRB are not identical. Through structure-function and co-expression analyses we have dissected the p107 molecule into two domains that independently are able to block cell cycle progression. One domain corresponds to the sequences needed for interaction with the transcription factor E2F, and the other corresponds to the interaction domain for cyclin A or cyclin E complexes. In cervical carcinoma cell line C33A, which was previously shown to be sensitive to p107 but resistant to pRB growth suppression, only the cyclin binding domain is active as a growth suppressor. Furthermore, we show that these two independent domains are functional in untransformed mouse fibroblasts. Together, these results provide experimental evidence for the presence of two functional domains in p107 and pinpoint an important functional difference between p107 and pRB.

3T3 Cells↗
PubMed1995

Persistent rubella infection after erroneous vaccination in an immunocompromised patient with acute lymphoblastic leukemia in remission.

A 16-year-old male patient with acute lymphoblastic leukemia in complete remission and on maintenance treatment with weekly oral methotrexate and daily oral 6-mercaptopurine for 3 months was immunized in error with the WI-RA 27/3-HDC live attenuated rubella vaccine. Increasing rubella HAI antibodies were noted from 3 to 7 months post-vaccination as well as high levels of IgM antibody up to 8 months in three different tests. High HAI antibody titers persisted for 12-18 months after vaccination. Persisting rubella virus was indicated by PCR detection of rubella-specific nucleic acid in whole blood, non-stimulated and stimulated mononuclear cells 8 months following vaccination. Further attempts to detect rubella virus RNA in two subsequent blood samples were negative. Since acute arthritis and arthralgia occurred in the second month (days 51-63) after vaccination, antileukemic chemotherapy had to be interrupted. Evidence of higher risk for chronic or relapsing rubella-associated arthropathy in immunologically compromised patients and the need to interrupt antileukemic chemotherapy should warrant immunoprophylaxis with polyvalent immune globulin in rubella-susceptible patients who are immunocompromised.

Adolescent↗
PubMed1995

Expression of adhesion molecules on human granulocytes after stimulation with Helicobacter pylori membrane proteins: comparison with membrane proteins from other bacteria.

Type B gastritis in its active form is characterized by a dense infiltration of the lamina propria with granulocytes. Since the bacterium Helicobacter pylori does not invade the epithelial barrier, a signaling pathway chemoattractive for granulocytes must exist across this mucosal boarder. One possible mechanism tested was whether granulocytes are directly activated by water-soluble membrane proteins (WSP) from H. pylori. These findings were compared with the effects of WSP from other bacteria (Helicobacter felis, Campylobacter jejuni, Escherichia coli, and Staphylococcus aureus). A unique activation pattern by H. pylori WSP was found. Like all other WSP tested, they induced an upregulation of CD11b but had no influence on CD11c and, most strikingly, CD62L expression. In contrast, E. coli WSP, e.g., not only induce a strong CD11b and CD11c expression but also lead to a loss in surface CD62L. The lack of CD62L shedding conserves rolling of granulocytes along the endothelium, creating a favorable precondition for granulocytes to stick more readily to activated endothelium after H. pylori stimulation via CD11b-CD54 receptor-counterreceptor interaction. This may explain why H. pylori infection is a very strong stimulus for granulocyte infiltration. The active fraction for the induction of CD11b on granulocytes is a heat- and protease-sensitive protein with a molecular mass between 30 and 100 kDa. One activation step involved may be the binding of WSP to CD15 determinants on granulocytes with subsequent induction of CD11b.

Antigens, Bacterial↗
PubMed1994

Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases.

In a joint prospective study in Germany and the United Kingdom between 1980 and 1993, 1373 women who had varicella and 366 who had herpes zoster during the first 36 weeks of gestation were followed up. 9 cases of congenital varicella syndrome were identified, all occurring after maternal varicella during the first 20 weeks of gestation. The highest risk (2.0%) was observed between 13-20 weeks gestation, with 7 affected infants identified among 351 pregnancies (95% CI of risk 0.8-4.1%). Only 2 cases of congenital varicella syndrome were identified among 472 pregnancies in which maternal varicella occurred before 13 weeks (observed risk 0.4%, 95% CI 0.05-1.5%). Herpes zoster in infancy was reported in 10 children whose mothers had had varicella in pregnancy. No infants with clinical evidence of intrauterine infection were born to the 366 women with herpes zoster in pregnancy (upper 95% confidence limit of estimated risk 1.0%). Varicella-zoster-specific IgM antibody was found at birth in 4 of 16 (25%) infants with clinical manifestations of intrauterine infection and persistent specific IgG antibody in 5 of 7 infants tested. The corresponding rates in asymptomatic infants whose mothers had varicella were 12% (76/615) and 7% (22/335) respectively. No serological evidence of intrauterine infection was found in infants who mothers had herpes zoster in pregnancy. In 97 pregnant women, varicella occurred after post-exposure prophylaxis with anti-varicella-zoster immunoglobulin. No cases of congenital varicella syndrome or zoster in infancy occurred in this group. Our estimates provide a sound basis for counselling women with varicella in pregnancy. Although the risk of congenital varicella syndrome is small, the outcome for the affected infant is so serious that a reliable method of prenatal diagnosis would be valuable. In the long term, prevention of maternal varicella would be an option if a safe and effective vaccine were to become routinely available.

Abortion, Spontaneous↗
PubMed1994

Immunohistological studies of complement activation after xenogeneic perfusion of a working heart model.

Transplantation of organs from one species to another leads to immediate hyperacute rejection. Activation of complement is one important factor involved in this process. Whether complement activation is induced by preformed natural antibodies (PNAbs) via the classical pathway or by an "activator surface" via the alternative pathway is unclear. In order to simulate the relevant clinical situation of animal donor/human recipient we perfused working porcine hearts ex vivo with human blood. This also offered the possibility to study the process of complement activation in a precisely defined system with human complement proteins. PNAb titer and complement lytic activity of the plasma were measured. Immunohistological stainings for IgG, IgM, C1q, C4, C3d, C5-9, factor B, and properdin were performed on tissue sections of the left ventricle. PNAb titer almost totally disappeared within the first 5 min of perfusion. Complement lytic activity of the classical pathway decreased similarly within the first 3 h of xenogeneic and autologous perfusion from 70% to 40%. More detailed immunohistological studies revealed positive staining for C3d on endothelium and myocardium of ex vivo perfused xenogeneic hearts. Complement-induced cytotoxicity was proven by the presence of C5-9 (membrane attack complex). However, hardly any C1q and C4 could be found in the ex vivo xenogeneic perfused hearts. Staining for factor B was positive and proved activation via the alternative pathway. Beyond that, the presence of properdin binding even indicated an upregulation of the alternative pathway C3 convertase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Detection of varicella zoster virus (VZV) DNA in fetal tissue by polymerase chain reaction.

Primary Varicella Zoster Virus (VZV) infection during pregnancy can be associated with severe fetal malformation. The virological diagnosis of congenital VZV syndrome has not yet been successful, however, as VZV could not be isolated from fetal tissue. We have now applied a polymerase chain reaction (PCR) assay to allow the detection of VZV DNA in fetuses whose mothers had acquired chickenpox in the first trimester of pregnancy. In 2 of 3 fetuses investigated viral DNA was identified by PCR independently in 2 laboratories, thus confirming a direct fetal VZV infection.

Base Sequence↗
PubMed1994

[Increase of post-infection cold agglutinins after infection with Mycoplasma pneumoniae, varicella-zoster and rubella virus].

Cold agglutinins (CA) are observed during acute infections as transiently occurring postinfection autoantibodies directed against erythrocyte antigens. Distinct infectious agents induce CA of distinct specificity. A common association is the infection with Mycoplasma pneumoniae and the production of CA with anti-I specificity. In infections with varicella-zoster virus (VZV) and rubella virus (RV) a few cases of CA appearance are reported, all of them showing specificity for the Pr antigens. We examined the frequency of CA with the anti-Pr specificity in patients suffering from acute infections with VZV and RV (table 1). The known association of anti-I in about 70% of the cases with acute Mycoplasma pneumoniae infection is confirmed by our results. The occurrence of CA in infections with VZV and RV is a rare event. Based on published data, the specificity of these CA apparently is anti-Pr. Three of 5 anti-Pr examples were found in newborns with rubella embryopathy. Possibly, anti-Pr can be observed more frequently in these patients compared to adults.

Adult↗
PubMed1993

Slow maturation of IgG1 avidity and persistence of specific IgM in congenital rubella: implications for diagnosis and immunopathology.

Without appropriately timed specimens, serological confirmation of congenital rubella infection may be a problem. We have compared the persistence of specific IgM and low avidity specific IgG1 in 141 sera from 120 cases of serologically confirmed congenital rubella infection with the known time scales for postnatal primary rubella. The results demonstrate that the maturation of the immune response to the rubella virus is abnormally slow in congenital rubella cases both in terms of the isotype switch and especially the development of high avidity specific IgG1. Thus avidity studies may permit serological confirmation of congenital rubella for longer than is possible with tests currently in use. The pathological implications of prolonged low avidity antibody production are discussed.

Aging↗