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Biomedical subjects

E Fischer

Publications and source records attributed to E Fischer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Vaccination against chlamydial genital tract infection after immunization with dendritic cells pulsed ex vivo with nonviable Chlamydiae.

Chlamydia trachomatis, an obligate intracellular bacterial pathogen of mucosal surfaces, is a major cause of preventable blindness and sexually transmitted diseases for which vaccines are badly needed. Despite considerable effort, antichlamydial vaccines have proven to be elusive using conventional immunization strategies. We report the use of murine bone marrow-derived dendritic cells (DC) pulsed ex vivo with killed chlamydiae as a novel approach to vaccination against chlamydial infection. Our results show that DC efficiently phagocytose chlamydiae, secrete IL-12 p40, and present chlamydial antigen(s) to infection sensitized CD4(+) T cells. Mice immunized intravenously with chlamydial-pulsed DC produce protective immunity against chlamydial infection of the female genital tract equal to that obtained after infection with live organisms. Immunized mice shed approximately 3 logs fewer infectious chlamydiae and are protected from genital tract inflammatory and obstructive disease. Protective immunity is correlated with a chlamydial-specific Th1-biased response that closely mimics the immune response produced after chlamydial infection. Thus, ex vivo antigen-pulsed DC represent a powerful tool for the study of protective immunity to chlamydial mucosal infection and for the identification of chlamydial protective antigens through reconstitution experiments. Moreover, these findings might impact the design of vaccine strategies against other medically important sexually transmitted diseases for which vaccines are sought but which have proven difficult to develop.

Adoptive Transfer↗
PubMed1998

Familial granulomatous arthritis (Blau syndrome) with granulomatous renal lesions.

Blau syndrome is a granulomatous disease of the skin, eyes, and joints, usually without visceral involvement. It is inherited in a autosomal dominant manner. The Blau susceptibility locus has been mapped to chromosome 16 p 12-q21. A recent report has added liver granulomata. We describe a family with Blau syndrome in whom 1 member had renal interstitial granulomata.

Acute Kidney Injury↗
PubMed1998

Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium.

Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria.

Bacterial Proteins↗
PubMed1998

Soluble CD21 (sCD21) forms biologically active complexes with CD23: sCD21 is present in normal plasma as a complex with trimeric CD23 and inhibits soluble CD23-induced IgE synthesis by B cells.

A soluble form of CD21 (sCD21) of 135 kDa is spontaneously released by human B and T lymphocytes upon shedding of the extracellular domain of the molecule. By Western blotting, we have now identified two forms of sCD21 of Mr 135 and 90 kDa in normal human serum. We further demonstrate that sCD21 circulates in a complexed form with cleavage fragments of C3 and CD23, two previously identified ligands of the membrane CD21 receptor. The CD23 molecule was in the form of a trimer in the soluble complex purified from plasma by affinity chromatography on anti-CD21 Sepharose. The serum sCD21 complex was also found to contain IgE. The presence of IgE and of CD21 in a soluble complex that contains trimeric CD23 as the only form of soluble CD23 (sCD23) is in agreement with a model in which two of the three lectin heads of CD23 bind to the Cepsilon3 domain of IgE, thus leaving one of the heads available for interaction with CD21. We further demonstrate that sCD21 inhibits sCD23-induced IgE synthesis by IL-4-stimulated B cells. The results indicate that sCD21 in plasma retains the ligand-binding properties of the membrane CD21 receptor and exhibits immunoregulatory properties that may be relevant to allergic and inflammatory disorders.

B-Lymphocytes↗
PubMed1997

Endothelial cells of the kidney vasa recta express the urea transporter HUT11.

The cell specific expression of the human urea transporter HUT11 in human and rat kidneys was investigated by immunochemistry and in situ hybridization. Using specific rabbit polyclonal antibodies directed against the N-terminal part and the C-terminal part of HUT11, we found that endothelial cells of medullary vasa recta (outer and inner medulla) express HUT11. In addition, an HUT11-related protein expressed by smooth muscle cells of cortical arterioles can be detected by the anti-HUT11 N-terminal peptide antibody but not the anti-HUT11 C-terminal peptide antibody. The endothelial expression of HUT11 was confirmed by double labeling with anti-CD31 and anti-von Willebrand factor antibodies. No HUT11-positive cells expressed alpha smooth muscle actin, Tamm Horsfall protein, cytokeratin 18, or CAM-L1, a marker of the principal cells of collecting ducts. Medullary vasa recta of developing and mature rat kidneys were also stained with the anti-HUT11 C-terminal peptide antibody. By in situ hybridization using a specific HUT11 35S-cDNA probe on human kidney sections, medullary vasa recta but not other renal structures were found to express HUT11 mRNA. We conclude that endothelial cells of medullary vasa recta express HUT11, a specific urea transporter, which may play a role in urea recycling within the kidney and in the mechanisms of urinary concentration and urea excretion.

Animals↗
PubMed1997

Peripartum cardiomyopathy.

Peripartum cardiomyopathy is an uncommon condition of unknown aetiology. Diagnosis requires exclusion of other causes of congestive cardiac failure and the demonstration of global ventricular dysfunction on echocardiography. Treatment consists od diuretics, vasodilators, digoxin and anticoagulants. Prognosis is related to recovery of ventricular function. The availability of cardiac transplantation has improved the outlook for those with persistent dysfunction.

Adult↗
PubMed1997

The alpha-galactosyl specific lectin from Artocarpus integrifolia distinguishes between two lymphoma lines with different metastatic potential.

A lectin purified from the seeds of the Vietnamese Artocarpus integrifolia distinguishes between the mouse T-cell lymphoma cell lines Eb and ESb, with low and high metastatic potential, respectively. It agglutinates Eb cells as well as human erythrocytes, but not ESb cells or the human colon carcinomas cells HT29. The haemagglutinin is specific for alpha-galactosyl residues and has a molecular mass of 62 kDa.

Agglutination Tests↗
PubMed1997

Activated skin mast cells are involved in murine hair follicle regression (catagen).

Increasing evidence supports a role for mast cells (MC) in the control of tissue remodeling. Using the cyclic growth and regression activity of the murine hair follicle (HF) as a model, we have previously demonstrated that MC are involved in regulating the HF transformation from resting (telogen) to active hair growth (anagen). In the present study, we investigated the potential role of skin MC in spontaneous HF regression (catagen), a rapid and highly controlled process of organ involution characterized by massive epithelial cell apoptosis. By histochemistry, immunohistochemistry, and electron microscopy, we first assessed the number, location, and granulation status of perifollicular MC during the anagen-catagen-telogen transformation of back skin HF. Spontaneous catagen induction was associated with a dramatic reduction of dermal MC numbers, preceded by an increase in the percentage of degranulated MC. In vivo, the MC-secretagogues substance P and adrenocorticotropic hormone induced premature and dystrophic catagen development in anagen HF, whereas inhibitors of MC degranulation retarded normal catagen development. Comparing HF cycling in MC-deficient WBB6F1-KitW/KitWv and congenic normal (+/+) mice, catagen development was retarded in the virtual absence of MC. These data support the notion that MC function as hair cycle regulators and are involved in the control of HF regression. The mouse model employed here offers an excellent tool for dissecting the physiologic role of MC as "central switchboards of tissue remodeling" in developmentally regulated systems, specifically in organ involution processes.

Adrenocorticotropic Hormone↗
PubMed1997

Neurotoxicity of paraquat and triphenyltin in the earthworm, Eisenia fetida Sav. A histo- and cytopathological study.

Neuropathological effects of the pesticides paraquat (PQ, a herbicide) and triphenyltin (TPT, a fungicide) were studied on the postclitellar segmental ganglia of juvenile E. fetida specimens using light and electron microscopic methods. Growth retardation of the worms in standard culture medium was used as quantitative marker of sublethal effect. There is a distinct neuron group in the segmental ganglia characterised by high sensitivity against PQ- and another one against TPT-toxication. However the marked histo- and neurocytopathological alterations were similar in PQ and TPT treated worms. Both chromatolysis and vacuolation of perikarya were revealed in sensitive neurons. Damaged cells were swollen and possessed degenerated rough endoplasmic reticulum cisternae. They were also characterised by swollen mitochondria, with electronlucent matrix and damaged inner membranes, and vesicular structures of various diameters as well as numerous lysosomes. Necrotic neurons with pyknotic nuclei and highly eosinophilic cytoplasm were also found in affected ganglia. Several dividing neurons were found in PQ-toxicated worms while no cell division occurred either in control or TPT-toxicated animals. The exact neurochemical and functional identification of PQ- and TPT-sensitive neurons needs further investigations.

Animals↗
PubMed1996

A recombinant Chlamydia trachomatis major outer membrane protein binds to heparan sulfate receptors on epithelial cells.

Chlamydial attachment to columnar conjunctival or urogenital epithelial cells is an initial and critical step in the pathogenesis of chlamydial mucosal infections. The chlamydial major outer membrane protein (MOMP) has been implicated as a putative chlamydial cytoadhesin; however, direct evidence supporting this hypothesis has not been reported. The function of MOMP as a cytoadhesin was directly investigated by expressing the protein as a fusion with the Escherichia coli maltose binding protein (MBP-MOMP) and studying its interaction with human epithelial cells. The recombinant MBP-MOMP bound specifically to HeLa cells at 4 degrees C but was not internalized after shifting the temperature to 37 degrees C. The MBP-MOMP competitively inhibited the infectivity of viable chlamydiae for epithelial cells, indicating that the MOMP and intact chlamydiae bind the same host receptor. Heparan sulfate markedly reduced binding of the MBP-MOMP to cells, whereas chondroitin sulfate had no effect on binding. Enzymatic treatment of cells with heparitinase but not chondroitinase inhibited the binding of MBP-MOMP. These same treatments were also shown to reduce the infectivity of chlamydiae for epithelial cells. Mutant cell lines defective in heparan sulfate synthesis but not chondroitin sulfate synthesis showed a marked reduction in the binding of MBP-MOMP and were also less susceptible to infection by chlamydiae. Collectively, these findings provide strong evidence that the MOMP functions as a chlamydial cytoadhesin and that heparan sulfate proteoglycans are the host-cell receptors to which the MOMP binds.

ATP-Binding Cassette Transporters↗
PubMed1996

Development of multiple organ dysfunction syndrome in critically ill patients with perforated viscus. Predictive value of APACHE severity scoring.

OBJECTIVE: To determine whether scoring on the Acute Physiology and Chronic Health Evaluation (APACHE) III at admission can predict the development of multiple organ dysfunction syndrome and mortality in critically ill surgical patients. DESIGN: Prospective, inception-cohort study. SETTING: Surgical intensive care unit of an urban, tertiary-care hospital. PATIENTS: One hundred fourteen critically ill patients with surgically treated perforated gastrointestinal viscus. INTERVENTIONS: Calculation of APACHE II and APACHE III scores 24 hours after admission to the surgical intensive care unit and serial quantitation of organ dysfunction for the duration of critical care according to two different predefined scoring systems. Patients were stratified by survival, the development of organ dysfunction, and colon vs noncolonic perforation. MAIN OUTCOME MEASURES: Hospital mortality, length of stay in the surgical intensive care unit, and the development of organ dysfunction or overt organ failure. RESULTS: The mean (+/- SEM) APACHE II and APACHE III scores were 17.4 +/- 0.6 (range, 6 to 37) and 59.0 +/- 2.2 (range, 15 to 141), respectively. The incidence of organ dysfunction was 73% (64% in survivors). All severity scores were identical for colon perforation and noncolonic perforation subgroups. Nonsurvivors invariably had organ dysfunction. Overall length of stay in the intensive care unit was 12.0 +/- 1.6 days (8.7 +/- 1.2 days for survivors and 22.7 +/- 5.0 days for nonsurvivors). The APACHE scores and organ dysfunction or failure scores were significantly higher in nonsurvivors, and APACHE scores were higher in survivors with organ dysfunction than in those without it. Significant linear relationships were identified for APACHE II vs APACHE III scores (R2 = .66) and for all four combinations of APACHE scores and organ dysfunction or failure scores (R2 = .43 to .52). By multivariate analysis of variance, independent predictors of organ dysfunction or failure were APACHE III, increased age, and a prolonged stay in the surgical intensive care unit, but not the type of perforation. Neither APACHE II or APACHE III predicted mortality independently. CONCLUSIONS: The development of multiple organ dysfunction syndrome correlated with higher APACHE III scores but was independent of the type of perforation. Only the development of overt multiple organ failure predicted death. Combined use of APACHE III and the multiple organ dysfunction score provides improved prediction of multiple organ dysfunction syndrome, but further enhancements are needed before prediction of outcome in individual patients is reliable.

APACHE↗
PubMed1996

Human lymphocytes shed a soluble form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that binds iC3b and CD23.

We report on a soluble (s) form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that is spontaneously released by B and T lymphocytes. Immunoprecipitation with anti-CD21 mAb of culture supernatants of surface and biosynthetically labeled B and T cell lines revealed a single band with an apparent molecular mass of 135 kDa. The molecule exhibited a molecular mass 10 kDa lower than that of membrane CD21. The release of soluble CD21 (sCD21) was time dependent and correlated with a parallel decrease in the expression of the membrane-associated molecule. The protein was also found in culture supernatants of tonsillar B cells and normal human thymocytes. Epitopic analysis using combinations of anti-CD21 monoclonal antibodies (mAb) indicated that sCD21 and membrane CD21 were similarly recognized by mAb directed against short consensus repeats (SCR) 1-2, SCR 4-5 and SCR 9-11. Affinity-purified sCD21 was capable of binding to purified human iC3b and to human recombinant CD23, as assessed by enzyme-linked immunosorbent assay and by using the BIAcore technology. In addition, normal human serum was found to contain a soluble form of CD21 that exhibited a similar molecular mass to that of the molecule shed by B and T cells in culture. The serum form of CD21 was recognized by all anti-CD21 mAb that we tested and showed a high reactivity with mAb directed against SCR 1-2. Our observations suggest that B and T cells shed the extracellular portion of CD21 and release a soluble molecule that retains the ligand-binding properties of CD21, thus having a potential role in immunoregulation.

B-Lymphocytes↗
PubMed1996

Ligation of CR1 (C3b receptor, CD35) on CD4+ T lymphocytes enhances viral replication in HIV-infected cells.

The present study provides evidence for a role of the C3b receptor, CR1 (CD35), in activation of HIV replication in CD4+ T lymphocytes. Ligation of CR1 with cross-linked anti-receptor MoAbs or with aggregated C3b enhanced transcription of viral genes and the release of p24 and RT activity from cultures of purified normal CD4+ T lymphocytes that had been infected with HIV-1 in vitro. No effect was observed upon ligation of CR2 (CD21), a C3 receptor that is also expressed on human CD4+ T cells. Cross-linking of CR1 also enhanced HIV replication in peripheral blood CD4+ lymphocytes isolated from HIV+ individuals. The enhancing effect of CR1 was not related to a mitogenic effect induced by stimulation of the receptor on T cells. The CR1 specificity of the enhancing effect was established by the observation that the addition of soluble recombinant CR1 to the cultures abolished the enhancement of p24 release induced by anti-CR1 MoAbs. Our results suggest that HIV replication may be triggered in resting HIV-infected CD4+ T lymphocytes through interaction with C3b-bearing immune complexes or particles.

Antibodies, Monoclonal↗
PubMed1996

Utility of illness severity scoring for prediction of prolonged surgical critical care.

OBJECTIVE: To determine whether APACHE III and multiple organ dysfunction syndrome scores can predict a prolonged length of stay for critically ill surgical patients in the intensive care unit. DESIGN: Prospective, inception-cohort study. SETTING: Surgical intensive care unit (SICU) of an urban, tertiary care hospital. PATIENTS: 2,295 consecutive admissions for critical surgical illness, postoperative complications, or postoperative monitoring in 2,058 patients. INTERVENTIONS: Calculation of Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores 24 hours after admission to the SICU. Serial quantitation of organ dysfunction for the duration of hospitalization according to the multiple organ dysfunction score. Patients were stratified by survival and time intervals for the duration of critical care, and followed until discharge or death. MAIN OUTCOME MEASURES: Hospital mortality and length of stay in the SICU. RESULTS: The mean APACHE II and APACHE III scores were 14.0 +/- 0.2 and 45.2 +/- 0.6 points, respectively (mean +/- SEM). The incidence of organ dysfunction was 43%, and the hospital mortality was 9.7%. The mean ICU length of stay was 6.1 +/- 0.2 days, but decreased progressively from 6.8 +/- 0.5 days in 1991 to 5.3 +/- 0.6 days in 1995 (p < 0.01) with no change in either illness severity or the number of admissions. By univariate analysis, increased length of stay in the ICU was associated with increasing APACHE scores, an increased incidence of emergency admissions, and the incidence and magnitude of organ dysfunction (all p < 0.01). Severity indices appeared to plateau in magnitude in patients whose ICU stay ultimately exceeded 21 days. By multivariate analysis of variance (MANOVA), independent predictors of a prolonged stay in the SICU were APACHE III (p = 0.0023), emergency admission (p = 0.0007), and the magnitude of organ dysfunction (p < 0.00001), but not APACHE II. Only an emergency admission (p = 0.0005) and the magnitude of organ dysfunction (p < 0.00001) predicted a prolonged stay independently in survivors. In contrast, only the admission APACHE III score(p = < 0.0001) and the magnitude of organ dysfunction (p = 0.0001) were independently predictive of mortality by MANOVA. CONCLUSIONS: The development of multiple organ dysfunction syndrome is a powerful predictor of a prolonged ICU course in critical surgical illness, even in survivors. Increased risk of a prolonged stay in the ICU plateaued at 21 days, making 21 days an appropriate definition of prolonged care for future studies. Predictive models should account for organ dysfunction and very long stays in future estimations. The combined use of APACHE III and the multiple organ dysfunction score may provide improved prediction of a prolonged stay in the ICU, but further enhancements are needed before prediction of outcome in individual patients is reliable.

APACHE↗
PubMed1996

Diagnosis and management of acute aortic valvular disruption secondary to rapid-deceleration trauma.

Acute aortic valve rupture with resultant aortic insufficiency is a rare complication of blunt trauma. We describe a case in which a patient fell 70 feet, sustaining avulsion of two leaflets of the aortic valve along with multiple other injuries, primarily orthopedic. Our case demonstrates that patients with acute aortic regurgitation can be managed nonoperatively if necessary in the acute setting, enabling management of other significant trauma. Subsequent semielective valvular replacement may be undertaken if other injuries must take precedence.

Accidental Falls↗
PubMed1996

Chronic intrathecal delivery of baclofen by a programmable pump for the treatment of severe spasticity.

The aim of this study was to determine the efficacy, safety, and cost-effectiveness of intrathecal baclofen delivered by a programmable pump for the chronic treatment of severe spasticity. Sixty-six patients with severe spasticity of spinal cord origin that was refractory to oral baclofen or who experienced intolerable side effects with this form of the drug were screened. The first nine participated in a double-blinded, randomized, placebo (normal saline)-controlled trial to determine response to a bolus dose of intrathecal baclofen. Subsequent patients were enrolled in an open-label treatment protocol without a placebo trial. All passed the screening, and the pump was implanted in 59 patients. Spasticity scores and medical costs before and after surgery were analyzed. In all patients, the mean Ashworth score for rigidity decreased from 4.3 preoperatively to 1.4 (p < 0.0005) with use of intrathecal baclofen. The spasm frequency score decreased from a mean of 3.6 to 0.5 (p < 0.0005). Activities of daily living, sleep, and skin integrity improved, and pain was eradicated in some. Constipation occurred in six patients. A reduction in dosage was necessitated by muscular hypotonia in three ambulatory patients, areflexic bladder and urinary retention in three others, and nausea, dizziness, and drowsiness in one. Catheter-related problems occurred 19 times in 15 patients. One pump was explanted because of infection in the pump pocket, and one was removed after it eroded through the skin. There were no pump failures. The use of intrathecal baclofen resulted in a decrease in the average length of subsequent hospitalizations. It is concluded that intrathecal baclofen delivered by an implanted programmable pump is a safe, effective, and cost-efficient method for treatment of severe intractable spinal spasticity.

Adolescent↗