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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
PubMed2001

Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets.

The cloning of the so-called 'parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify its therapeutic potential in a number of diseases.

Animals↗
PubMed2001

Dysesthesia perceived as painful spasticity: A report of 3 cases.

Lesions of the central nervous system often involve the pyramidal tracts and the sensory pathways to produce spasticity, paresthesias, and dysesthesia. Three patients with intractable spasticity were treated with intrathecal baclofen. Two had an implanted Medtronic SynchroMed pump for long-term delivery of the muscle relaxant. The third patient had undergone a screening trial in which the baclofen was delivered into the intrathecal space through a lumbar catheter. All had excellent relief of spasms on clinical examination, but they reported painful spasms particularly at night. Two of the patients were successfully treated for dysesthesia.

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PubMed2001

Chlamydia pneumoniae major outer membrane protein is a surface-exposed antigen that elicits antibodies primarily directed against conformation-dependent determinants.

The major outer membrane protein (MOMP) of Chlamydia trachomatis serovariants is known to be an immunodominant surface antigen. Moreover, it is known that the C. trachomatis MOMP elicits antibodies that recognize both linear and conformational antigenic determinants. In contrast, it has been reported that the MOMP of Chlamydia pneumoniae is not surface exposed and is immunorecessive. We hypothesized that the discrepancies between C. trachomatis and C. pneumoniae MOMP exposure on intact chlamydiae and immunogenic properties might be because the focus of the host's immune response is directed to conformational epitopes of the C. pneumoniae MOMP. We therefore conducted studies aimed at defining the surface exposure of MOMP and the conformational dominance of MOMP antibodies. We present here a description of C. pneumoniae species-specific monoclonal antibody (MAb), GZD1E8, which recognizes a conformational epitope on the surface of C. pneumoniae. This MAb is potent in the neutralization of C. pneumoniae infectivity in vitro. Another previously described C. pneumoniae species-specific monoclonal antibody, RR-402, displayed very similar characteristics. However, the antigenic determinant recognized by RR-402 has yet to be identified. We show by immunoprecipitation of C. pneumoniae with GZD1E8 and RR-402 MAbs and by mass spectrometry analysis of immunoprecipitated proteins that both antibodies GZD1E8 and RR-402 recognize the MOMP of C. pneumoniae and that this protein is localized on the surface of the organism. We also show that human sera from C. pneumoniae-positive donors consistently recognize the MOMP by immunoprecipitation, indicating that the MOMP of C. pneumoniae is an immunogenic protein. These findings have potential implications for both C. pneumoniae vaccine and diagnostic assay development.

Amino Acid Sequence↗
PubMed2001

Genetics and regulation of chitobiose utilization in Borrelia burgdorferi.

Borrelia burgdorferi spends a significant proportion of its life cycle within an ixodid tick, which has a cuticle containing chitin, a polymer of N-acetylglucosamine (GlcNAc). The B. burgdorferi celA, celB, and celC genes encode products homologous to transporters for cellobiose and chitobiose (the dimer subunit of chitin) in other bacteria, which could be useful for bacterial nutrient acquisition during growth within ticks. We found that chitobiose efficiently substituted for GlcNAc during bacterial growth in culture medium. We inactivated the celB gene, which encodes the putative membrane-spanning component of the transporter, and compared growth of the mutant in various media to that of its isogenic parent. The mutant was no longer able to utilize chitobiose, while neither the mutant nor the wild type can utilize cellobiose. We propose renaming the three genes chbA, chbB, and chbC, since they probably encode a chitobiose transporter. We also found that the chbC gene was regulated in response to growth temperature and during growth in medium lacking GlcNAc.

Acetylglucosamine↗
PubMed2000

Pilot study on erbium laser phacoemulsification.

PURPOSE: To investigate the suitability of erbium laser phacoemulsification for cataract surgery using a prospective pilot study. DESIGN: Prospective, single-center, nonrandomized clinical trial. PATIENTS AND METHODS: Slit-lamp microscopy, keratometry, best-corrected visual acuity, refraction, pachymetric corneal thickness, endothelial cell density, and intraocular pressure were assessed before surgery and on the first, fourth, fourteenth, and the sixtieth day after surgery in 40 eyes of 34 patients with senile cataract (17 males with a mean age of 67.3 years; 17 females with a mean age of 73.2 years). All operations were performed by one surgeon (HH) using the MCL-29 erbium laser (Aesculap-Meditec, Jena, Germany). The nuclear sclerosis grade ranged from 0 to 4. MAIN OUTCOME MEASURES: Primary outcome measures were defined as the ability to emulsify the lens nucleus under clinical conditions and the occurrence of side effects. Secondary outcome measures included the change in visual acuity, refraction, intraocular pressure, corneal thickness, and endothelial cell density. RESULTS: Complete emulsification of the lens nucleus using the erbium laser was achieved in 36 of 40 eyes (90%; nuclear sclerosis grade, 0-3). Partial emulsification of the nucleus was possible in two cases with grade 3 nuclear sclerosis, in one case of grade 2 nuclear sclerosis, and in one case of cataract with grade 4 nuclear sclerosis. Mean phacoemulsification time was 3 minutes, and the total applied energy equaled 38.5 J. The postoperative changes in visual acuity, spherical and astigmatic refraction, and intraocular pressure were found to be the same as with ultrasonic phacoemulsification. The decrease in the density of endothelial cells (by 0.96%) was not statistically significant. Posterior capsule ruptures occurred in three eyes early in the series. There were no further vision-threatening complications. CONCLUSIONS: Erbium laser phacoemulsification is effective for lenses with mild to moderate nuclear sclerosis. For higher grades of nuclear sclerosis, further improvements in technical and surgery-related parameters are required.

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PubMed2000

Cepaea hortensis agglutinin-I, specific for O-glycosidically linked sialic acids, selectively labels endothelial cells of distinct vascular beds.

The lectin Cepaea hortensis agglutinin-I (CHA-I) binds to O-glycosidically linked sialic acids with previously characterized specificity. Employing histochemistry, we demonstrate that CHA-I is a useful probe for detecting sialic acids in formalin-fixed human tissues in a specific manner. It stains the endothelium of arteries and veins in all tissues examined, and labels the capillaries in distinct vascular beds including the brain, colon, thyroid, pituitary, and adrenal. By contrast, the endothelial sinusoids in the liver, spleen, and bone marrow remained unstained. The staining pattern of CHA-I overlaps with the distribution of the sialomucin and L-selectin ligand podocalyxin, which includes positivity of podocytes and interstitial but not glomerular capillaries. CHA-I-positive epithelial structures were found in the lung, liver and kidney. Colon carcinoma cells were labelled with CHA-I but not haemangiosarcomas. In summary, CHA-I is a useful tool for detecting O-glycosidically linked sialic acids in formalin-fixed tissues, and a potentially powerful tool for the isolation and characterization of unknown sialomucins in normal and eventually in diseased tissues.

Animals↗
PubMed2000

Tumoral calcinosis of the temporomandibular joint region.

A rare case of tumoral calcinosis, discovered in the medial pterygoid muscle and around the temporomandibular joint on a routine panoramic radiograph is presented. CT was found to be ideal for the determination of the exact location of the calcifications. The differential diagnosis of tumoral calcinosis is discussed.

Adult↗
PubMed2000

An exposure system to study the effects of water-soluble gases on PM-induced toxicity.

An aerosol generation and exposure system to evaluate the role of water-soluble gases in particulate matter (PM)-induced injury was designed, built, and validated by generating test atmospheres to study the role of hydrogen peroxide in PM-induced toxicity. In this system, particle number concentration, size distribution, hydrogen peroxide concentration, and water concentration can all be varied. An ammonium sulfate aerosol with mass median diameter 0.46 +/- 0.01 microm was used as a model atmospheric aerosol because ammonium sulfate is a major component of the fine aerosol, and the water uptake of ammonium sulfate aerosol is well characterized. The following four test atmospheres were generated: (1) ammonium sulfate aerosol, (2) an aerosol containing hydrogen peroxide and ammonium sulfate, (3) vapor-phase hydrogen peroxide, and (4) particle-free air. All test atmospheres were maintained at a relative humidity of 85%. Particle size distribution, number concentration, total hydrogen peroxide concentration, temperature, and relative humidity were measured continuously in the exposure chamber. The gas-particle partitioning of hydrogen peroxide was calculated using total hydrogen peroxide concentration, the Henry's law constant for hydrogen peroxide in water, and aerosol water content. We found that the aerosol generation system produced stable concentrations throughout the 2-hour exposures.

Aerosols↗
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↗