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Biomedical subjects

E Fischer

Publications and source records attributed to E Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Abnormal expression of glomerular basement membrane laminins in membranous glomerulonephritis.

BACKGROUND: Proteinuria associated with glomerular diseases is secondary to alterations of the charge-selective and/or size-selective properties of the glomerular basement membrane (GBM), but molecular alterations that are responsible for these functional changes are still poorly understood. Analysis of mice harbouring a null mutation in the gene encoding the beta 2 chain of laminin has suggested that the presence of abnormal laminin chains within the GBM can be responsible for proteinuria. METHODS: We have investigated whether abnormal laminin ss chains could be detected by immunohistochemistry within the GBM of patients with proteinuria and minimal change disease (five patients), focal and segmental glomerulosclerosis (five patients), or primary membranous glomerulonephritis (10 patients). Three patients with mesangiocapillary glomerulonephritis and three patients with IgA nephropathy were also studied as controls. RESULTS: We showed that the GBM of all 10 patients with membranous glomerulonephritis, but not of patients with other glomerulopathies, contained laminin beta 1, which is normally expressed only during metanephros development. The re-expression of the beta 1 chain of laminin was not associated with that of the embryonic alpha 1 chain of type IV collagen, or with the loss of expression of vimentin and synaptopodin, two markers of differentiated podocytes. CONCLUSIONS: The presence of new laminin isoforms within the GBM of patients with membranous glomerulonephritis could play a role in the occurrence of proteinuria, by modifying either the sieving properties of the GBM or the interactions between podocytes and the GBM.

Adult↗
PubMed2000

Alterations of preliminary readings on radiographic examinations minimally affect outcomes of trauma patients discharged from the emergency department.

BACKGROUND: We hypothesized that trauma patients could be discharged safely from the emergency department (ED) before the availability of official readings for their radiologic examinations. We also sought to determine whether trauma patients were more prone to alterations of preliminary interpretations than other ED patients. METHODS: Alterations of preliminary readings (PR) for patients discharged from the ED were reviewed. If the official readings conflicted with the PR used for the patient's disposition, attempts were made to contact the patient and provide the appropriate follow-up. Data recorded included the type of radiographic examination, the presence of a missed injury, and the follow-up. By using institutional data, the incidence of inaccurate PR were compared for trauma patients and other ED patients (chi2 test, Fisher exact test, p < 0.05). RESULTS: Between January of 1998 and December of 1998, 102 of 38,260 discharged ED patients had official readings differing from PR. Forty-three of the changed readings involved 42 of the 1,073 discharged trauma patients, who were more likely to harbor inaccurate PR (<0.0001) than other discharged ED patients. Twenty-eight altered readings involved plain films and 15 involved computed tomographic scans. The most common altered readings involved computed tomographic scans of the head and face (n = 13). Twelve missed injuries were detected, most commonly related to a missed injury of the extremity (7 cases). Nine other cases involved the detection of incidental pathologic conditions. Eight patients required repeat ED visits for clinical and radiographic evaluation, and one patient required subsequent hospital admission. CONCLUSION: Discharged trauma patients are more likely to harbor alterations of preliminary interpretations than other ED patients. Although the official readings for these trauma patients will occasionally reveal previously undetected pathologic conditions, the majority of such cases can be managed with outpatient follow-up.

Diagnostic Errors↗
PubMed2000

Segment diffusion and flip-flop spin diffusion in entangled polyethyleneoxide melts: A field-gradient NMR diffusometry study

Chain dynamics in melts of entangled polyethyleneoxide melts has been investigated using fringe field nuclear magnetic resonance diffusometry. As already demonstrated in our previous work, intermolecular flip-flop spin diffusion strongly influences spin echo attenuation for long diffusion times and high molecular weights. The experimental data have been evaluated taking this phenomenon quantitatively into account. Predictions of the reptation model for the correspondingly modified time and molecular weight dependences of the effective segment diffusion coefficient are presented and compared with experimental results. While the ordinary Rouse model totally fails to explain the experimental data, a satisfactory qualitative description is provided on the basis of the tube/reptation model. However, the fitted parameter values turned out to be inconsistent with known properties of this polymer. This in particular refers to the mean squared chain end-to-end distance divided by the molecular weight, for which neutron-scattering values are available in the literature. Relative to those results, the value evaluated from our NMR diffusometry data on the basis of the tube/reptation model turned out to be much too large.

Journal Article↗
PubMed2000

Ultrastructural analysis of developmental events in Chlamydia pneumoniae-infected cells.

Chlamydia pneumoniae is an obligate intracellular parasite with a developmental cycle believed to be common to all members of the genus Chlamydia. We present a detailed description based on transmission and scanning electron microscopy of temporal events and inclusion structures throughout the C. pneumoniae AR-39 developmental cycle.

Chlamydophila pneumoniae↗
PubMed1999

Identification of surface molecules on salivary glands of the mosquito, Aedes aegypti, by a panel of monoclonal antibodies.

Malaria transmission by the mosquito vector requires sporozoite invasion into mosquito salivary glands. Parasites probably enter the glands by specific receptor-ligand interactions with molecules on the surface of the glands. We have undertaken the characterization of salivary gland surface molecules of Aedes aegypti to identify candidate receptors for Plasmodium gallinaceum sporozoite invasion. Monoclonal antibodies (mAbs) were generated against antigen enriched for salivary gland membranes and basal lamina. A panel of 44 mAbs were generated that bound to surface molecules of mosquito tissues. Twenty-four mAbs bound exclusively to salivary glands, six bound to salivary glands and ovaries, one bound to salivary gland and midgut, and 13 bound to all tissues tested. We present data on the immunolocalization and biochemical characteristics of the antigens. Many of the salivary gland-specific mAbs bound preferentially to the median and distal lateral lobes of the salivary glands, indicating that there are anatomical region-specific biochemical differences on the gland surface. These lobes of the salivary glands are the preferential sites of malaria sporozoite invasion. Therefore, antigens specific for these regions are promising candidate receptors for sporozoite invasion. The present identification of surface molecules of mosquito salivary glands by means of monoclonal antibodies represents the first description of individual molecules on the mosquito salivary gland surface. This work lays the basis for further studies on the molecular mechanisms involved in malaria sporozoite invasion of mosquito salivary glands.

Aedes↗
PubMed1999

SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein.

Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium-dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

[Erbium laser phacoemulsification--a clinical pilot study].

INTRODUCTION: From August 1997 to March 1998, we performed a prospective pilot study to examine erbium laser phacoemulsification in cataract surgery under clinical conditions and to determine the side effects of this method. PATIENTS AND METHOD: 34 patients (40 eyes) with senile cataract were recruited. Slit lamp findings, keratometry, best corrected visual acuity, refraction, pachymetry, endothelial cell count and intraocular pressure were determined preoperatively and on 1st, 4th, 14th and 60th postop day according to a standardised protocol (single pulse energy between 10 and 20 mJ, frequency of application 60 Hz, average phaco time 3 min, total energy 38.5 mJ). The operations were done with the erbium laser system MCL 29, Aesculap-Meditec Co., Jena, Germany. RESULTS: A total emulsification of the nucleus was possible in 36 of 40 eyes (90%) (nucleus hardness between 0 and 3). A partial emulsification of the nucleus in nucleus hardness 3 was possible in 2 eyes, in nucleus hardness 4 in 1 eye and in nucleus hardness 2 in 1 eye (4 eyes--10%). Visual acuity increased from 0.3 preop to 0.8 two months postop (median). Intraocular pressure decreased from 16 mm Hg preoperatively to 13 mm Hg two months postoperatively (median). The increase of corneal thickness was not statistically significant compared to baseline. The decrease of endothelial cell count was 0.96%. Postoperative complications which are not known in ultrasonic phacoemulsification did not appear in erbium laser phacoemulsification. CONCLUSION: Erbium laser phacoemulsification is a surgical method that makes the emulsification of softer nuclei under clinical conditions possible with a low rate of complications also in the beginning of the learning curve. For higher nucleus hardnesses, technical and surgical parameters have to be optimised. Advantages of erbium laser phacoemulsification compared to ultrasonic phacoemulsification are less energy transmission into the eye, no heating of anterior chamber, impossibility of corneal burns and easier access in eyes that are deep into the orbit. Especially advantageous is the high protection of endothelium by erbium laser phacoemulsification. A prospective controlled comparative study to ultrasonic emulsification is desirable.

Aged↗
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↗