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Biomedical subjects

D Neumann

Publications and source records attributed to D Neumann.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparison of persistent thallium perfusion defects by quantitative washout analysis with thallium reinjection in patients with coronary artery disease.

Thallium reinjection can improve the detection of severely ischemic viable myocardium in patients with coronary artery disease. However, a disadvantage of this method is that it requires the acquisition of 3 separate sets of images and the administration of an additional dose of the radiotracer. Alternatively, quantitative analysis of the regional myocardial washout of thallium-201 can be easily obtained from the conventional postexercise and redistribution images without additional imaging time or radiation exposure to the patient. To determine whether this method can predict the results of thallium reinjection, this study analyzed thallium-201 images of 31 patients who had persistent perfusion defects in qualitative exercise/delayed redistribution single-photon emission computed tomographic thallium studies and who underwent thallium reinjection. The quantitative mean radioactive counts of each myocardial segment that had a persistent perfusion defect in the initial and delayed redistribution on 4-hour short-axis tomographic slices were measured to derive a delayed/initial ratio, and these values were compared with the results of thallium reinjection. The delayed/initial ratio was 1.06 +/- 0.22 in 39 segments that improved, versus 0.58 +/- 0.18 in 43 segments without improvement after reinjection (p < 0.001). Thirty-eight of the 39 segments that improved had a ratio of > or = 0.75, versus only 3 of the 43 segments that showed no improvement (sensitivity, 98%; specificity, 91%). The correlation between the delayed/initial ratio and reinjection results was equally high at any segment location or severity. It is concluded that quantitative regional thallium washout analysis predicts the results of thallium reinjection in segments with persistent thallium defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Interleukin-1-induced cyclooxygenase 2 expression is suppressed by cyclosporin A in rat mesangial cells.

The immunosuppressive drug cyclosporin A (CsA) has considerable nephrotoxic side effects which seem to be related to its interference with the synthesis of vasoactive prostanoids. Therefore, the molecular mechanism of the effect of CsA on the synthesis of prostaglandin E2 (PGE2) was investigated in rat renal mesangial cells (RMC). CsA effectively inhibited the PGE2 synthesis induced by inflammatory cytokines such as interleukin 1 (IL-1) or tumor necrosis alpha (TNF alpha). The induction by IL-1 and the inhibition by CsA were reflected in the enzyme activity of the cyclooxygenase. The changes in activity could be correlated with the expression of the inducible cyclooxygenase isoform (COX2), which is characterized by its 4.4 kb mRNA: the expression of this enzyme was enhanced by IL-1 and suppressed by CsA on the mRNA and protein level as determined by Northern and Western blot analyses. Suppression of COX2 mRNA was also observed when the message was induced by LPS or ionophore A23187. The expression of the basal cyclooxygenase isoform (COX1), which was constitutively expressed in proliferating mesangial cells, was not affected by IL-1 or CsA. Interferon gamma, which did not induce prostaglandin synthesis or influence COX mRNA expression, augmented the expression of MHC antigens in RMC. This induction was insensitive to CsA treatment. We could thus show that the inducible cyclooxygenase isoform in mesangial cells is a molecular target for CsA providing a possible mechanism for the interference of the drug with the balance of vasoactive prostanoids.

Animals↗
PubMed1993

Both megakaryocytopoiesis and erythropoiesis are induced in mice infected with a retrovirus expressing an oncogenic erythropoietin receptor.

Increasing direct and indirect evidence suggests that erythropoietin (Epo) promotes both erythropoiesis and megakaryocytopoiesis. Here we report that, in mice infected with a recombinant spleen focus-forming retrovirus (SFFV) expressing an oncogenic erythropoietin receptor (EpoR), there was an increase in platelet count preceding the ensuing erythrocytosis. Concurrently, there was a substantial increase in splenic megakaryocytes. Culture of the bone marrow and spleen cells from infected mice showed enhanced numbers of multipotent megakaryocytic progenitors. DNA polymerase chain reaction analysis of individual megakaryocyte-containing colonies showed recombinant SFFV (SFFVcEpoR) proviral integration. Immunofluorescence of spleen sections showed overexpression of EpoR protein in the megakaryocytes. Mice infected with a strain of SFFV also developed splenic megakaryocytosis without activating overexpression of the EpoR in megakaryocytes. This in vivo system shows that a relationship between erythropoiesis and thrombopoiesis can exist at the level of the Epo-EpoR signaling pathway. Also, SFFV-based vectors may be excellent vehicles for the introduction of genes into multipotent, hematopoietic progenitors, in vitro.

Animals↗
PubMed1993

Intermediates in degradation of the erythropoietin receptor accumulate and are degraded in lysosomes.

The erythropoietin receptor (EPO-R) is synthesized in transfected Ba/F3 cells as a major 64-kDa endoglycosidase H (Endo H)-sensitive species, with a single N-linked oligosaccharide, and a minor 62-kDa unglycosylated form. Approximately half of the newly made EPO-R is processed to a mature 66-kDa form with a Golgi-processed Endo H-resistant oligosaccharide, of which only a minor fraction is expressed at the cell surface. Both the Endo H-sensitive and the Endo H-resistant forms of the receptor have a half-life of 45-60 min (Yoshimura, A., D'Andrea, A. D., and Lodish, H. F. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 4139-4143). The mature, Endo H-resistant form of the EPO-R appears to be degraded in lysosomes or in other acidic organelles, since receptor degradation is blocked by treatment with NH4Cl, chloroquine, or leupeptin. A fraction of the Endo H-resistant EPO-R molecules is cleaved, generating two fragments of 46 and 39 kDa. The sizes of these fragments and their reactivities with carboxyl-terminal-specific antibodies indicate that the receptor is cleaved at two sites in the exoplasmic domain, 7 kDa apart, and carboxyl-terminal to the N-glycosylation site. Both fragments are membrane anchored and are probably formed in a late or post-Golgi compartment, since their formation is blocked by incubation of cells at 20 degrees C or by incubation with brefeldin A. These membrane-anchored COOH-terminal fragments are probably degraded in lysosomes or in other acidic vesicles as cell fractionation demonstrates that they colocalize with lysosomes, and similar to the intact EPO-R, their degradation is inhibited by NH4Cl. Finally, double labeling immunofluorescence experiments demonstrate that in NH4Cl-treated cells both intact mature EPO-R and the 46- and 39-kDa fragments accumulate in lysosomes and presumably are normally degraded there. The sensitivity of the EPO-R to endoproteolytic cleavages in its exoplasmic domain may relate to its low surface expression and to its extreme metabolic instability.

3T3 Cells↗
PubMed1993

The effectiveness of daily wear contact lenses for the correction of infantile aphakia.

OBJECTIVE: To evaluate the effectiveness and safety of daily wear contact lenses in the treatment of infantile aphakia. DESIGN: A study of prognosis using a cohort followed up for a mean of 58 months. SETTING: All operations, contact lens care, and follow-up were conducted at a university referral center. PATIENTS: Of 111 children undergoing surgery for cataract between 1980 and 1990, 51 (68 eyes) met the criteria of age younger than 2 years at the time of surgery and of cataract of nontraumatic origin. Patients were evaluated for visual acuity, complications, number of contact lenses worn per year, and changes in contact lens refractive power per month. A subgroup of 28 eyes of patients undergoing surgery before age 7 months and followed up for at least 24 months was studied. INTERVENTION: Following cataract surgery, all patients were fitted with daily wear contact lenses. MAIN OUTCOME MEASURE: Final visual acuity and complications were studied. The distribution of mean contact lens power for each month of age was determined. RESULTS: During the follow-up period, no serious complications were encountered. The visual acuity outcome was better following bilateral cataract surgery than unilateral surgery (P < .001 using chi 2 analysis) and was comparable with that achieved with extended wear contact lenses. CONCLUSION: Daily wear contact lenses were found to be safe and effective in the treatment of infantile surgical aphakia. The daily care was easily learned by the parents.

Aphakia, Postcataract↗
PubMed1993

HSP68--a DnaK-like heat-stress protein of plant mitochondria.

A 68-kDa heat-stress protein (HSP68) has been purified from cell-suspension cultures of tomato (Lycopersicon peruvianum L.). Antibodies raised against HSP68 cross-react with the Escherichia coli heat-stress protein DnaK. HSP68 was found to be a hydrophilic, ATP-binding protein. Immunological analysis of subcellular fractions and immunogold-labelling of ultrathin sections showed consistently that HSP68 is localized in the mitochondrial matrix. In-vitro translation experiments indicated that HSP68 is synthesized as a precursor protein. Immunoscreening of cDNA libraries from tomato and potato (Solanum tuberosum L.) led to the isolation of corresponding cDNA clones. The deduced amino-acid sequences show strong relationships to the DnaK-like proteins from bacteria and organelles of eukaryotic cells. The protein HSP68 is constitutively expressed, but its synthesis is increased during heat stress in all cells of higher plants investigated so far.

Adenosine Triphosphate↗
PubMed1993

Antimicrobial activities of black-pigmented gram-negative anaerobes.

The antimicrobial activities of Prevotella intermedia and Porphyromonas gingivalis isolates were tested against other species of Gram-positive and Gram-negative anaerobes as well as against each other. Generally, Pr. intermedia possessed significantly higher antimicrobial activity than P. gingivalis. The strongest activity of P. gingivalis towards Gram-negative anaerobes was directed against Pr. intermedia. Cross-sensitivity between both species was observed with strains from different lesions. Antimicrobial activity towards strains of the same species was detected only with Pr. intermedia. No correlations were found between plasmid content and antimicrobial activity. It was concluded that the inhibitory potency of Pr. intermedia could be one reason for the high proportion of black-pigmented Gram-negative anaerobes in the subgingival flora of periodontitis lesions.

Anti-Bacterial Agents↗
PubMed1993

Internal sclerostomy using laser ablation of dyed sclera in glaucoma patients: a pilot study.

Twelve eyes of 12 patients with refractory glaucoma were treated with internal sclerostomy using laser ablation of dyed sclera. The technique involves iontophoretic impregnation of the sclera at the limbal region with 1% methylene blue and subsequent delivery of a pulsed dye laser beam to the stained area through a goniolens. The red wavelength of 664 nm generated by the laser is maximally absorbed by the stained sclera and creates a through and through sclerostomy. Successful complete sclerostomy was achieved in seven eyes (58.3%) but there was some reduction of intraocular pressure (IOP) in all cases. Mean prelaser IOP (of all 12 eyes) was 36.6 mm Hg and 1 hour after therapy it was reduced to 20.0 mm Hg. At the end of the follow-up period (mean 16 months) the mean IOP was 23.7 mm Hg; five eyes (41%) maintained their IOP below 22 mm Hg, and the average number of medications per eye came down from 3.25 to 2.25 per eye. Transient corneal burns with Descemet's membrane folds adjacent to the laser impact zone were detected in eight eyes (67%). No major complications like IOP spike, hyphaema, iridodialysis, or retinal detachment have been detected. Clear cornea and dark blue scleral staining are essential for the mechanical success of this procedure. Gonioscopic laser internal sclerostomy of methylene blue dyed sclera is technically feasible and the preliminary results of IOP control in refractory glaucoma are promising. Modifications of the iontophoresis process and laser parameters are currently under investigation in order to improve these results.

Adult↗
PubMed1993

Corneal changes in chondrodysplasia punctata syndrome.

A child with chondrodysplasia punctata syndrome is presented. In addition to the bilateral congenital cataracts that have been described previously in this syndrome, this child had bilateral corneal punctate erosions. These corneal abnormalities, which to the best of our knowledge have not been described in this syndrome before, persisted for at least three years.

Abnormalities, Multiple↗
PubMed1992

How the mongoose can fight the snake: the binding site of the mongoose acetylcholine receptor.

The ligand binding site of the nicotinic acetylcholine receptor (AcChoR) is within a short peptide from the alpha subunit that includes the tandem cysteine residues at positions 192 and 193. To elucidate the molecular basis of the binding properties of the AcChoR, we chose to study nonclassical muscle AcChoRs from animals that are resistant to alpha-neurotoxins. We have previously reported that the resistance of snake AcChoR to alpha-bungarotoxin (alpha-BTX) may be accounted for by several major substitutions in the ligand binding site of the receptor. In the present study, we have analyzed the binding site of AcChoR from the mongoose, which is also resistant to alpha-neurotoxins. It was shown that mongoose AcChoR does not bind alpha-BTX in vivo or in vitro. cDNA fragments of the alpha subunit of mongoose AcChoR corresponding to codons 122-205 and including the presumed ligand binding site were cloned, sequenced, and expressed in Escherichia coli. The expressed protein fragments of the mongoose, as well as of snake receptors, do not bind alpha-BTX. The mongoose fragment is highly homologous (greater than 90%) to the respective mouse fragment. Out of the seven amino acid differences between the mongoose and mouse in this region, five cluster in the presumed ligand binding site, close to cysteines 192 and 193. These changes are at positions 187 (Trp----Asn), 189 (Phe----Thr), 191 (Ser----Ala), 194 (Pro----Leu), and 197 (Pro----His). The mongoose like the snake AcChoR has a potential glycosylation site in the binding site domain. Sequence comparison between species suggests that substitutions at positions 187, 189, and 194 are important in determining the resistance of mongoose and snake AcChoR to alpha-BTX. In addition, it was shown that amino acid residues that had been reported to be necessary for acetylcholine binding are conserved in the toxin-resistant animals as well.

Amino Acid Sequence↗
PubMed1992

Mutations in the Trp-Ser-X-Trp-Ser motif of the erythropoietin receptor abolish processing, ligand binding, and activation of the receptor.

The erythropoietin receptor (EPOR) is a member of the newly identified cytokine receptor superfamily. A common sequence motif, Trp-Ser-X-Trp-Ser (WSXWS), near the transmembrane domain is highly conserved in this family. To determine the function of this motif, we constructed deletion and insertion mutations in this part of the EPOR and introduced them into an interleukin-3 (IL-3)-dependent hematopoietic Ba/F3 cell line. Cells expressing the wild-type EPOR displayed 1,500 erythropoietin (EPO)-binding sites/cell with a single affinity of about 300 pM and proliferate in the presence of IL-3 or EPO. Ba/F3 cells expressing receptors mutated in the WSXWS motif displayed little EPO binding on the cell surface and did not grow in the presence of EPO. The mutant receptors were retained in the endoplasmic reticulum (ER) and, as such, were unable to bind EPO. A single Gly insertion between the two WS sequences caused defects in receptor structure and function similar to mutations lacking all or part of the WSXWS motif. The EPOR can be activated, resulting in proliferation independent of EPO either by an Arg129 to Cys point mutation or by association with the Friend spleen focus-forming virus (SFFV) envelope glycoprotein gp55. Introduction of the point mutation (Arg129 to Cys) did not activate any of the receptors mutated in the WSXWS motif. Moreover, gp55 did not activate the mutant receptors in Ba/F3 cells. Our study indicates that the WSXWS motif is critical for protein folding, ligand-binding, and signal transduction.

Amino Acid Sequence↗
PubMed1991

Internal sclerostomy with laser: a new approach to glaucoma surgery.

The creation of a fistula that permits controlled flow of aqueous from the anterior chamber to the subconjunctival space has been and remains the main technical goal of glaucoma filtering surgery. Currently, most complications are secondary to the surgical manipulation of the conjunctiva (mainly leakage from bleb and conjunctival fibrosis) or flattening of the anterior chamber. To overcome this problem, new methods are evolving in which the fistula is created from within the eye, with no conjunctival dissection. The performing of the sclerostomy by means of externally delivered laser energy is a further step in the same direction.

Glaucoma↗
PubMed1991

Trabeculectomy with anterior vitrectomy in aphakic and pseudophakic glaucoma.

In 15 eyes with uncontrolled aphakic/pseudophakic glaucoma, trabeculectomy with anterior vitrectomy was performed. Mean pre-operative intraocular pressure (IOP) was 38.2 +/- 6.7 mmHg and mean post operative IOP was 19.3 +/- 5.2 mmHg after follow-up of 11.2 2 months. The anterior chamber maintainer technique during vitrectomy has been employed. Success rate (IOP less than 21 mmHg with or without glaucoma medication) was 80%. Visual acuity remained unchanged in 4 eyes, improved in 5 eyes and worsened in 6 eyes. Postoperative complications included: two eyes with cystoid macular edema, two eyes with choroidal effusion and prolonged hypotony, one eye with self-absorbing vitreous hemorrhage and one eye with some opacification of the corneal graft. In aphakic/pseudophakic glaucoma where vitreous is filling the anterior chamber--a combined trabeculectomy with anterior vitrectomy is indicated for removal of vitreous from the sclerostomy site with better aqueous flow through the sclerostomy and adequate control of IOP.

Adult↗
PubMed1991

T-cell antigenic sites involved in myasthenia gravis: correlations with antibody titre and disease severity.

We have evaluated the ability of eight synthetic peptides corresponding to selected regions of the alpha-subunit from human (H) or Torpedo (T) acetylcholine receptor (AChR) to stimulate proliferative responses of peripheral blood lymphocytes (PBL) and thymic cells from patients with Myasthenia Gravis (MG) in comparison to healthy controls. Using PBL, two of the peptides were most reactive: in the 40 myasthenic patients tested, peptide 169-181 (H) induced significant proliferative responses in 10 patients and peptide 351-368 (H) in five, while there was no response in any of the 34 healthy controls tested. Interestingly, clear associations between proliferation to peptides and clinical data were observed. Indeed, among responding patients, all presented thymic hyperplasia and most showed a high anti-AChR Ab titre and/or a severe form of the disease. In addition, responses to AChR cytoplasmic sequences were observed only in severely affected patients. Correlation with HLA-DR haplotype, sought in a subgroup of patients, indicated that response to 169-181 (H) is associated with HLA-DR5 in the patients presenting a high anti-AChR antibody titre. Using thymic lymphocytes, few responses were obtained with the human peptides, suggesting that the frequency of autoreactive cells is lower than in the blood. Similar to PBL, responses to peptides were observed only with lymphocytes isolated from hyperplastic thymuses. The correlations observed between responses to peptides and clinical parameters underline the pathophysiological relevance of our data and indicate that pathogenic and nonpathogenic T-cell antigenic sites involved in the anti-AChR response could be identified by this approach.

Adult↗
PubMed1990

[Epsilon aminocaproic acid for management of traumatic hyphema with large blood clot in the anterior chamber].

Epsilon aminocaproic acid (EACA) is an antifibrinolytic agent currently used in the management of traumatic hyphema. It is effective in reducing the rebleed rate, but a long-standing blood clot in the anterior chamber predisposes to complications, such as corneal blood staining and elevated intraocular pressure. We assume that a large blood clot in the anterior chamber might be a contraindication to the use of EACA.

Adult↗