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Biomedical subjects

M Bayer

Publications and source records attributed to M Bayer.

At least 73 records · Page 4Linked to original sources

Cell type-specific MxA-mediated inhibition of measles virus transcription in human brain cells.

Measles virus (MV)-specific transcription in human brain cells is characterized by particularly low abundances of the distal mRNAs encoding the MV envelope proteins. Similar transcriptional restrictions of the closely related vesicular stomatitis virus have been observed in mouse fibroblasts constitutively expressing the interferon-inducible MxA protein (P. Staeheli and J. Pavlovic, J. Virol. 65:4498-4501, 1991). We found that MV infection of human brain cells is accompanied by rapid induction and high-level expression of endogenous MxA proteins. After stable transfection of MxA, human glioblastoma cells (U-87-MxA) released 50- to 100-fold less infectious virus and expression of viral proteins was highly restricted. The overall MV-specific transcription levels were reduced by up to 90%, accompanied by low relative frequencies of the distal MV-specific mRNAs. These restrictions were linked to an inhibition of viral RNA synthesis and not to a decreased stability of the viral RNAs. Our results indicate that expression of MxA is associated with transcriptional attenuation of MV in brain cells, thus probably contributing to the establishment of persistent MV central nervous system infections. In addition, the mechanism of MxA-dependent resistance against MV infection, in contrast to that of vesicular stomatitis virus, is cell type specific, because an inhibition of MV glycoprotein synthesis independent of transcriptional alterations was observed in MxA-transfected human monocytes (J. J. Schnorr, S. Schneider-Schaulies, A. Simon-Jödicke, J. Pavlovic, M. A. Horisberger, and V. ter Meulen, J. Virol. 67: 4760-4768, 1993).

Animals↗

Escherichia coli as a biologically active ingredient of suppositories. Solid phase extraction and quantification in a double antibody ELISA.

Techniques for isolation and quantification of an active ingredient of biological origin from a pharmaceutical product (Posterisan suppositories) were developed. By means of ELISA (enzyme-linked immunosorbent assay) in connection with a computerized evaluation, the antigenic material, a bacterial culture suspension (BCS) of Escherichia coli as a raw material was shown to be specifically and reproducibly detectable and quantifiable. As a limit of detection, a bacteria concentration of 6 x 10(4) cells/ml was determined, corresponding to 0.02% of the concentration in the product. After treating of the suppositories with organic solvents, the E. coli antigens were extracted with silica columns. The complete validations of both methods, the ELISA itself and the extraction procedure of the antigens from the matrix, in accordance with pharmaceutically accepted principles are presented. The eventual application of the new technique to the analysis of other pharmaceuticals with similar ingredients as well as the possibility of substituting conventional methods like total cell counting is discussed.

Antibodies, Bacterial↗

Juvenile chronic arthritis--bone mineral density in relation to corticosteroid therapy.

Bone demineralization often accompanies juvenile chronic arthritis (JCA). Fourteen patients with confirmed diagnosis of JCA had their bone mineral density (BMD) measured with the use of dual photon X-ray absorptiometry. The results obtained were compared to the Lunar BMD DPXA standards. Seven patients received Prednisone in doses of more than 0.16 mg/kg/day for more than 6 months and 7 patients (sex and age matched) never received any steroids at all. In the first group BMD was decreased in 7 patients (100%), in the second group BMD was mildly decreased in 2 patients (28%). Due to the difference in BMD in both groups, it is obvious that corticosteroids have substantial influence on bone demineralization in JCA.

Adolescent↗

Calciuria in children with juvenile chronic arthritis.

Demineralization of bone is a frequent finding in children with juvenile chronic arthritis (JCA). Recently there have been reports about hypercalciuria accompanying JCA. This is believed to be associated with increased bone resorption due to cytokines and immobility of the patients and steroid treatment. In 12 patients with confirmed diagnosis of JCA basic biochemical indices of bone metabolism, were performed (S-Ca, P, ALP, U-Ca/U-creatinine, U-P). Bone mineral density (BMD) was measured using DPXA method and results obtained were compared to the Lunar BMD DPXA standards. In spite of decreased BMD, no significant hypercalciuria was found and other mentioned biochemical indices of bone and mineral metabolism were normal as well.

Adolescent↗

Bone and mineral metabolism in transient hyperphosphatasaemia.

Transient hyperphosphatasaemia (TH) is a benign disorder characterized by transient elevation of S-ALP activity not exceeding duration of 4 months in children under 5 years of age, with elevated activity of bone isoenzymes of ALP with no signs of bone or liver disease and variable unrelated symptoms. We observed 19 children with TH and in 3 patients with markedly elevated S-ALP activity we found increased excretion of urinary hydroxyproline, suggesting increased bone resorption followed by bone formation. In 3 children with history of TH, bone mineral density (BMD) was measured and found to be normal. Transient increased bone resorption followed by bone formation during the course of TH can not be ruled out, but this has no negative impact on BMD.

Alkaline Phosphatase↗

Two cases of pseudohypoparathyroidism in adolescent boys.

Pseudohypoparathyroidism (PHP) is characterized by end organ resistance to parathyroid hormone (PTH). PHP type Ia consists of Albright's osteodystrophy and resistance to PTH. In PHP type Ib physical appearance is normal and there is no response to PTH in U-cAMP excretion. In PHP type II both physical appearance and U-cAMP response to PTH infusion are normal. Two adolescent patients with severe hypocalcaemia were treated in our department. The first boy was admitted because of low back pain, latent tetany and recurrent collapsing, the second one due to Grand mal epilepsia. S-Ca concentrations were very low (1.1 and 1.03 mmol/l respectively), CT of the brain revealed multiple calcifications in basal ganglia and S-PTH concentrations were above upper reference level. Therefore the diagnosis of PHP was established. In the absence of skeletal malformations the most probable diagnosis is PHP Ib or II. Clinical state of the boys has dramatically improved after calcium and vitamin D supplementation.

Adolescent↗

Effect of hypertonic sodium bicarbonate in the treatment of moderate-to-severe cyclic antidepressant overdose.

The objective of this study was to characterize the effect of intravenous hypertonic sodium bicarbonate (NaHCO3) administration in patients with moderate-to-severe cyclic antidepressant (CA) overdose. We reviewed charts of all 91 patients given the diagnosis of CA overdose in the University of California Los Angeles (UCLA) Emergency Medicine Center (EMC), who either died in the EMC or were admitted to the medical intensive care unit (MICU), and who received NaHCO3 in the EMC between 1980 and 1988. Twenty-four other patients with the same EMC diagnosis were admitted to the MICU during this period but did not receive NaHCO3. The response of blood pressure, electrocardiographic parameters, and mental status to serum alkalinization with NaHCO3 were evaluated. Major morbidity and mortality were recorded for all patients. Hypotension was corrected within 1 hour in 20 of 21 (96%) patients, QRS prolongation corrected in 39 of 49 (80%), and mental status improved in 40 of 85 (47%). There was one death, in a patient who was moribund on arrival to the EMC. No complications were attributable to the administration of NaHCO3. NaHCO3 seems to improve hypotension and normalize QRS duration rapidly in most patients treated, and improve mental status changes in almost one half. Serum alkalinization with NaHCO3, in conjunction with appropriate supportive care, seems to limit major morbidity and mortality effectively in patients with serious CA overdose.

Adolescent↗

Ribonucleoprotein complexes of hepatitis delta virus.

Human hepatitis delta virus (HDV) is a subviral satellite agent of hepatitis B virus (HBV). The envelope proteins of HDV are provided by the helper virus, HBV, but very little is known about the internal structure of HDV. The particles contain multiple copies of the delta antigen and an unusual RNA genome that is small, about 1,700 nucleotides in length, single stranded, and circular. By using UV cross-linking, equilibrium density centrifugation, and immunoprecipitation, we obtained evidence consistent with the interpretation that delta antigen and genomic RNA form a stable ribonucleoprotein (RNP) complex within the virion. Furthermore, electron-microscopic examination of the purified viral RNP revealed a roughly spherical core-like structure with a diameter of 18.7 +/- 2.5 nm. We also isolated HDV-specific RNP structures from the nuclei of cells undergoing HDV genome replication; both the genome and antigenome (a complement of the genome) of HDV were found to be in such complexes. From the equilibrium density analyses of the viral and nuclear RNPs, we were able to deduce the number of molecules of delta antigen per molecule of HDV RNA. For virions, this number was predominantly ca. 70, which was larger than for the nuclear RNPs, which were more heterogeneous, with an average value of ca. 30.

Animals↗

Spontaneous and differentiation-dependent regulation of measles virus gene expression in human glial cells.

The expression of measles virus (MV) in six different permanent human glioma cell lines (D-54, U-251, U-138, U-105, U-373, and D-32) was analyzed. Although all cell lines were permissive for productive replication of all MV strains tested, U-251, D-54, and D-32 cells spontaneously revealed restrictions of MV transcription similar to those observed for primary rat astroglial cells and brain tissue. In vitro differentiation of D-54 and U-251 cells by substances affecting the intracellular cyclic AMP level caused a significant reduction of the expression of the viral proteins after 18, 72, and 144 h of infection. This pronounced restriction was not paralleled to a comparable level by an inhibition of the synthesis and biological activity in vitro of virus-specific mRNAs as shown by quantitative Northern (RNA) blot analyses and in vitro translation. The block in viral protein synthesis could not be attributed to the induction of type I interferon by any of the substances tested. Our findings indicate that down-regulation of MV gene expression in human brain cells can occur by a cell type-dependent regulation of the viral mRNA transcription and a differentiation-dependent regulation of translation, both of which may be crucial for the establishment of persistent MV infections in the central nervous system.

Cell Differentiation↗

Assembly of hepatitis delta virus particles.

Hepatitis delta virus (HDV) is a subviral satellite of hepatitis B virus (HBV). Since the RNA genome of HDV can replicate in cultured cells in the absence of HBV, it has been suggested that the only helper function of HBV is to supply HBV coat proteins in the assembly process of HDV particles. To examine the factors involved in such virion assembly, we transiently cotransfected cells with various hepadnavirus constructs and cDNAs of HDV and analyzed the particles released into the medium. We report that the HDV genomic RNA and the delta antigen can be packaged by coat proteins of either HBV or the related hepadnavirus woodchuck hepatitis virus (WHV). Among the three co-carboxy-terminal coat proteins of WHV, the smallest form was sufficient to package the HDV genome; even in the absence of HDV RNA, the delta antigen could be packaged by this WHV coat protein. Also, of the two co-amino-terminal forms of the delta antigen, only the larger form was essential for packaging.

Antigens, Viral↗

Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran.

The underlying mechanisms of the beneficial therapeutic effects of small-volume resuscitation with hyperosmolar solutions for treatment of hypovolemic shock are still poorly understood. Using the dorsal skinfold chamber model and intravital fluorescence microscopy, we investigated the effects of hyperosmolar saline dextran on ischemia-reperfusion injury in striated skin muscle of awake normovolemic golden hamsters. Test solutions (4 ml/kg body wt i.v.) were administered 2 min before reperfusion after 4 h of pressure-induced ischemia. In animals receiving 0.9% saline (control), we observed a drastic enhancement of leukocyte rolling along and sticking to the endothelium of postcapillary venules 0.5 h after reperfusion. Postischemic leukocyte rolling and sticking were significantly reduced when animals were treated with 7.2% saline alone (HSS), 10% Dextran 60 in 0.9% saline (HDS), or 10% Dextran 60 in 7.2% saline (HHS). In control animals, capillary perfusion was reduced to approximately 60% of preischemic values 0.5 h after reperfusion. Concomitantly, leakage of the macromolecule fluorescein isothiocyanate-dextran (5 mg in 0.1 ml saline i.v., M(r) 150,000) into the perivascular space increased from 0% before ischemia to approximately 12% at 0.5 h reperfusion. In contrast, when animals were treated with HSS, HDS, or HHS before reperfusion, capillary perfusion decreased to a significantly minor extent of approximately 15%, and macromolecular leakage was slightly increased to approximately 5%. Our results suggest that hyperosmolar saline dextran effectively attenuates postischemic microvascular disturbances elicited by ischemia-reperfusion, presumably through reduction of postischemic leukocyte-endothelium interaction and capillary swelling.

Animals↗

[Surgical treatment of sequelae of injuries of the thoracolumbar spine].

The authors describe surgical techniques used in 48 patients with sequelae of injuries of the thoracolumbar spine and the achieved results. Twenty-one patients were treated by an anterior operation, 14 by posterior operation and 13 a combination of both. The anterior operation involved 1) simple stabilization by autografts or 2) release, correction of the kyphosis and fusion and 3) elimination of the affected body of the vertebra and replacement by a massive allograft. If reliable stability was not achieved, instrumentation was added. In posterior operation they always stabilized the spine by instrumentation and added fusion. In the remaining patients they combined the posterior and anterior operation. The anterior operations were, if necessary, supplemented by decompression, when using the posterior approach they decompressed by the posterolateral route. As to complications which called for re-operation, instrumentation failed once and twice a pseudoarthrosis was repaired. Pain disappeared or receded substantially in 86%. Of 30 patients with a partial nervous lesion 14 (47%) improved, in two slight deterioration occurred.

Adolescent↗

[Sequelae of injuries of the thoracolumbar spine and indications for surgery].

Inadequate treatment of a fresh injury of the thoracolumbar spine of failure or surgical treatment may lead to substantial restriction of the physical activity of the patient. This is due to posttraumatic kyphosis, possibly its progression, instability, painfulness and a persisting or progressing neurological finding. Forty-eight patients with unstable fracture of the thoracolumbar spine were, except one operated patient, treated originally by conservative methods, 15 of them were moreover subjected to isolated laminectomy. In 30 patients a partial nervous lesion was involved. The majority of patients in the group subjected to laminectomy had a more severe kyphotic deformity which more frequently was progressive. The authors indicated surgery in 18 patients (37%) on account of pain, in 14 (29%) on account of instability, in 12 (25%) on account of progressing kyphosis and in 4 (8%) on account of an increasing nervous deficit. They included 26 patients with persisting partial nervous affections in the group with instability and progressing kyphosis, as anterior compression of the dural sac was revealed and they indicated release of nervous structures as part of the surgical operation. In the remaining partial neurological lesions with a patient spinal canal decompression was not indicated.

Adolescent↗