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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 217 records · Page 12Linked to original sources
PubMed1991

Aspartylglucosaminuria: cDNA encoding human aspartylglucosaminidase and the missense mutation causing the disease.

We have isolated a 2.1 kb cDNA which encodes human aspartylglucosaminidase (AGA, E.C. 3.5.1.26). The activity of this lysosomal enzyme is deficient in aspartylglucosaminuria (AGU), a recessively inherited lysosomal accumulation disease resulting in severe mental retardation. The polypeptide chain deduced from the AGA cDNA consists of 346 amino acids, has two potential N-glycosylation sites and 11 cysteine residues. Transient expression of this cDNA in COS-1 cells resulted in increased expression of immunoprecipitable AGA protein. Direct sequencing of amplified AGA cDNA from an AGU patient revealed a G----C transition resulting in the substitution of cysteine 163 with serine. This mutation was subsequently found in all the 20 analyzed Finnish AGU patients, in the heterozygous form in all 53 carriers and in none of 67 control individuals, suggesting that it represents the major AGU causing mutation enriched in this isolated population. Since the mutation produces a change in the predicted flexibility of the AGA polypeptide chain and removes an intramolecular S-S bridge, it most probably explains the deficient enzyme activity found in cells and tissues of AGU patients.

Amino Acid Sequence↗
PubMed1991

Gene regulation by interleukin 6.

Interleukin 6 (IL-6) is a central alarm hormone of the mammalian body. During acute and chronic inflammations, it induces acute phase plasma protein synthesis by liver hepatocytes, modulates the immune response and participates in the regulation of body temperature (fever). In addition, it is a growth factor for certain tumor cells, such as myeloma cells. The details of the IL-6 signal transduction mechanism are unknown. We have contributed to this problem at 2 levels: (a), we have mapped an IL-6-response element (IL-6-RE) in the 5' flanking region of the alpha 2-macroglobulin gene (alpha 2M), a prototype rat liver acute phase gene. This element, CTGGGA, serves as a binding site for nuclear factors that facilitate hormone induced transcription. We have begun to characterize these factors from hepatic cells and demonstrated that they undergo characteristic IL-6-induced changes. Similar factors were also discovered in human Burkitt tumor derived cell lines (B cells). These bound at the IL-6-RE of the rat alpha 1M gene and formed indistinguishable protein DNA complexes, as the corresponding hepatic factors. Thus, common elements probably operate in the IL-6 signal transduction cascade in liver cells and B cells; (b), we have cloned the rat liver IL-6 receptor (IL-6-R) and derived its amino acid sequence. It was 53% identical to the human leukocyte IL-6-R and all functional domains were highly conserved. Therefore, the cell-type specific responses to IL-6 in liver cells and lymphocytes were probably not due to cell-type specific forms of the receptor, but to other so far unknown elements of the signal transduction cascade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The Interleukin-6-dependent DNA-binding protein gene (transcription factor 5: TCF5) maps to human chromosome 20 and rat chromosome 3, the IL6 receptor locus (IL6R) to human chromosome 1 and rat chromosome 2, and the rat IL6 gene to rat chromosome 4.

Using two panels of somatic cell hybrids segregating either human or rat chromosomes, the gene encoding the interleukin-6-dependent DNA-binding protein, also called liver activator protein (designated transcription factor 5: TCF5), was assigned to human chromosome 20 and to rat chromosome 3. The TCF5 gene might be identical with the NF-IL6 gene. The locus encoding the IL6 receptor gene (IL6R) was localized to human chromosome 1 and rat chromosome 2. An IL6R-like (IL6RL) locus was also assigned to human chromosome 9. In addition, the rat interleukin-6 (IL6) gene was assigned to rat chromosome 4. These mapping data allow one to extend comparison between the rat, mouse, and human gene maps.

Animals↗
PubMed1991

Alterations of cellular immune response during intensive training of event horses.

During strenuous exercise of horses that are prepared for international Three-Day-Events a significant decrease in the in vitro killing rate of phagocytosed yeast cells by the blood granulocytes has been observed. Other immunological parameters, such as the phorbolmyristate dependent chemiluminescence in granulocytes and the mitogenic stimulation of blood lymphocytes, remained unchanged.

Animals↗
PubMed1991

Comparison of alpha 1 adrenoceptors in the prostate capsule of men with symptomatic and asymptomatic benign prostatic hyperplasia.

The objective of this study was to compare the binding and functional properties of alpha 1 adrenoceptors in prostate capsules obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH) undergoing simple retropubic prostatectomy and cystoprostatectomy respectively. Saturation experiments using 125I-Heat demonstrated that the density and binding affinity of alpha 1 adrenoceptors in the prostate capsules obtained from men with symptomatic and asymptomatic BPH were similar. Non-cumulative dose response experiments using phenylephrine demonstrated that the magnitude of the contractile response to phenylephrine was 4-fold greater in the prostate capsules from men with symptomatic BPH than from those with asymptomatic BPH. The EC50 of phenylephrine in the prostate capsules of men with symptomatic and asymptomatic BPH was similar. A correlation between alpha 1 adrenoceptor density and phenylephrine Emax was not observed, implying that either alpha 1 adrenoceptors are not localised exclusively to the prostate smooth muscle or that spare alpha 1 adrenoceptors exist. This study suggests that the neuropharmacological properties of the prostate capsule may play a significant role in the development of infravesical obstruction in the ageing male population.

Dose-Response Relationship, Drug↗
PubMed1991

Autologous blood stem cell (ABSCT) versus purged bone marrow transplantation (pABMT) in standard risk AML: influence of source and cell composition of the autograft on hemopoietic reconstitution and disease-free survival.

Complete and sustained hemopoietic function following myeloablative therapy can be successfully achieved by autologous transfusion of blood derived hemopoietic stem cells. It was the purpose of this study to compare autologous blood stem cell transplantation (ABSCT) in 20 patients with autologous transplantation of a mafosfamide purged marrow (pABMT) in 23 patients; all were transplanted in first complete remission (CR) of acute myelogenous leukemia (AML) using the same pretransplant regimen (14.4 Gy total body irradiation and 200 mg/kg cyclophosphamide). The autografts, mostly differing in source of hemopoietic stem cells, cell composition and CFU-GM number, were evaluated for their ability to reconstitute hemopoiesis and induce long-term disease-free survival (DFS). Prior to harvest, hemopoietic stem cells were mobilized by inducing transient myelosuppression (ara-C 100 mg/m2 every 12 h s.c. days 1-5 and daunorubicin 45 mg/m2, days 3 and 4) followed by an overshooting of peripheral stem cell concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Non-contact measurement of the increase in pulp temperature during thermal debonding].

Thermal debonding of ceramic brackets is now used for some time. In this context the possibility of a thermal damage of the pulp is one of the main questions. With the aid of a touchless infrared thermography device (SST/Theta 1,000; Heimann, FRG-Wiesbaden) the consequences of thermal debonding with the "Ceramic Debonding Unit" (Dentaurum, Pforzheim) have been studied. A use according to the manufacturer's device led to temperature changes up to 3 degrees C as maximum. Therefore our in vitro results indicate that the orderly use of the system is safe for the pulp. If the debonding fails, the temperature increase is much higher if the resistance wire is left in place. The influence of different composites is discussed.

Bicuspid↗
PubMed1991

[Radiotherapy of solitary and multiple eosinophilic granulomas of bone (stage I)].

Between 1957 and 1990 15 patients with solitary (stage Ia by Greenberger) and 2 patients with multiple (stage Ib) eosinophilic granuloma of the bone were treated by radiotherapy in 18 locations after previous surgery. The doses applied varied from 6 Gy to 42 Gy (median for patients under 18 years: 8 Gy, for patients over 18 years: 30 Gy). Median follow-up was 9 years (range, 0.3-33 years). Local control rate and survival were 100%. Three patients with granuloma developed a second granuloma within 13 years after primary diagnosis (two bone manifestations, one cutaneous manifestation). Long-term follow-up of patients with solitary eosinophilic granuloma is necessary.

Adolescent↗
PubMed1991

[Changes in the early auditory evoked potentials during premature infancy, infancy and early childhood].

We report on the derivation of the early acoustic evoked potentials (EAEP) in 498 healthy normotrophic infants between the 32nd post-conceptional week and the end of the 3rd year of life. The changes of the wave latencies and interpeak intervals in different age periods until they reached the constant values found in adults are followed by 1528 potential derivations. The varying rate of maturation of the auditory pathway in the brain stem can be followed up well by the potential patterns. The time around the 34th post-conceptional week is characterized by a maturation episode of central and peripheral auditory pathway portions. The extrauterine matured normotrophic preterm infant shows statistically significantly longer latencies of waves III and V and a longer interpeak interval I-V in comparison with normotrophic term neonates. Gestational age, birth weight and Apgar score of the preterm infant had no influence on the behaviour of the EAEP. After the 38th post-conceptional week practically only the maturation of the central auditory pathway portion takes place: the main portion of the latency shortenings of III and V and IPI I-V is applicable to the 1st year of life. The maturation is an individually characterized progressive process of varying speed with no fixed age for its completion. Thus the adult wave V latency was reached in 8% of the 4- to 6-month-old children, and in 57% by the end of the 1st year of life. The adult IPI I-V values were reached in 42% of the 10- to 12-month-old children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Molecular cloning, characterization and functional expression of the rat liver interleukin 6 receptor.

A series of cDNA clones coding for the rat liver interleukin 6 receptor (IL6-R) were isolated from an acute-phase library. The identity of the clones was established (a) by DNA sequence analysis and comparison with the known human leukocyte IL6-R and (b) by demonstrating that the clones generated specific IL6 ligand binding activity and IL6-dependent regulation of acute-phase gene control elements after transfection into appropriate recipient cells. Two types of cDNA clones were obtained corresponding to two mRNA species of different length, both encoding an identical protein of 462 amino acid residues. The two prototype clones, pRIL6RC.21 and pRIL6RC.6 contained 3'-untranslated regions of 550 and 3100 nucleotides, respectively. The sequence motifs TTATTTAT and ATTTA associated with the regulation of mRNA stability and translation efficiency were present only in the longer mRNA species. The deduced amino acid sequence of the rat liver IL6-R was 53% identical with the human leukocyte IL6-R. Both receptors contained conserved structural features in their extracellular domains, including the signal peptide, a C2 domain characteristic of the immunoglobulin superfamily, and two domains shared among members of a family of cytokine and growth factor receptors. The strongly conserved intracellular portion of the rat liver IL6-R lacked recognizable signal transduction domains. The cDNA clones were used to demonstrate that rat liver IL6-R mRNA concentrations were increased 4.2-fold at 12 h after the induction of an experimental acute-phase response. Clone pRIL6R.21ex, but not clone pRIL6RC.6ex, generated specific IL6 ligand binding activity after transfection into human Jurkat cells that lack the endogenous IL6-R. By contrast, only pRIL6RC.6ex reconstituted a response of human Hep3B-2 and HepG2 hepatoma cells to mouse IL6. These human hepatoma cells were highly responsive to human IL6 but did not respond to physiologic concentrations of murine IL6. After cotransfection with pRIL6RC.6ex and plasmids containing the chloramphenicol acetyltransferase reporter gene under the control of IL6 response elements of acute-phase plasma protein genes, these cells showed a strong stimulation of the reporter gene by recombinant mouse IL6. Thus, both cell surface ligand binding activity and the complete IL6 signal cascade terminating in the transcriptional induction of IL6-dependent promoters were successfully reconstituted. Therefore, both IL6-R mRNA species code for functionally active receptor, depending on the target cell, but only the longer mRNA species coded for significant receptor levels in human hepatoma cell lines.

Amino Acid Sequence↗
PubMed1990

Isolation and characterization of cardiac amyloid in familial amyloid polyneuropathy type IV (Finnish): relation of the amyloid protein to variant gelsolin.

Amyloid subunit protein was isolated from familial amyloid polyneuropathy type IV (Finnish type) cardiac tissue and purified to homogeneity. N-terminal amino acid sequence analysis shows that the amyloid protein is a fragment of the inner region of human gelsolin. When compared with the predicted sequence of human plasma gelsolin, the amyloid protein contains an asparagine-for-aspartic acid substitution at position 15 corresponding to residue 187 of the secreted protein. Antibodies raised against the amyloidogenic region of gelsolin specifically stained the amyloid deposited in tissues in familial amyloidosis type IV. The results show that the subunit amyloid protein in familial amyloid polyneuropathy type IV represents a unique type of amyloid derived from a variant (Asn-187) gelsolin molecule by limited proteolysis.

Aged↗
PubMed1990

Comparative gas phase and pulsed liquid phase sequencing on a modified Applied Biosystems 477A sequencer.

A simple and inexpensive modification of the Applied Biosystems 477A sequencer, to run in the pulsed liquid-phase and in the gas-phase mode of the Edman chemistry, is described. This modification is especially useful for sequencing samples on polyvinylidene difluoride (PVDF) membranes. Additional carriers are required if a sample on a PVDF membrane is sequenced with the pulsed liquid-phase degradation program of the 477A. In the gas-phase mode no such carriers are needed. This eliminates time-consuming preconditioning sequencer cycles and reduces the sequencer background. In addition, initial coupling yields in the gas-phase mode exceeded those in the pulsed liquid-phase mode, whereas the average repetitive yields were similar. Samples spotted onto glass fiber filters pretreated with polybrene and samples spotted or electroblotted onto PVDF membranes were examined. A number of advantages of the gas-phase mode are presented.

Amino Acid Sequence↗
PubMed1990

Sequence of cDNA for rat cystathionine gamma-lyase and comparison of deduced amino acid sequence with related Escherichia coli enzymes.

A cDNA clone for cystathionine gamma-lyase was isolated from a rat cDNA library in lambda gt11 by screening with a monospecific antiserum. The identity of this clone, containing 600 bp proximal to the 3'-end of the gene, was confirmed by positive hybridization selection. Northern-blot hybridization showed the expected higher abundance of the corresponding mRNA in liver than in brain. Two further cDNA clones from a plasmid pcD library were isolated by colony hybridization with the first clone and were found to contain inserts of 1600 and 1850 bp. One of these was confirmed as encoding cystathionine gamma-lyase by hybridization with two independent pools of oligodeoxynucleotides corresponding to partial amino acid sequence information for cystathionine gamma-lyase. The other clone (estimated to represent all but 8% of the 5'-end of the mRNA) was sequenced and its deduced amino acid sequence showed similarity to those of the Escherichia coli enzymes cystathionine beta-lyase and cystathionine gamma-synthase throughout its length, especially to that of the latter.

Amino Acid Sequence↗
PubMed1990

Finnish hereditary amyloidosis. Amino acid sequence homology between the amyloid fibril protein and human plasma gelsoline.

Amyloid fibrils were isolated from the kidney of a patient with Finnish hereditary amyloidosis. After solubilization of the fibrils in guanidine-HCl, fractionation by gel filtration, and purification by reverse-phase high-performance liquid chromatography, a homogeneous amyloid protein with an apparent Mr of 9000 was obtained. The protein was subjected to enzymatic digestion by trypsin and endoproteinase Lys-C. The amino acid sequences were determined for 6 of the released peptides and they were all found to be identical to the reported, deduced primary structure of human plasma gelsoline in the region of amino acids 235-269. The results show that the amyloid fibril protein in Finnish hereditary amyloidosis represents a new type of amyloid protein that shows amino acid sequence homology with gelsoline, an actin-modulating protein.

Aged↗
PubMed1990

Binding and functional properties of doxazosin in the human prostate adenoma and canine brain.

The binding and functional properties of doxazosin were characterized in the canine brain and human prostate. 3H-Doxazosin binding sites were characterized in canine brain and human prostate homogenates using saturation experiments. The binding of 3H-doxazosin in the canine brain was consistently saturable and of high affinity. The mean equilibrium dissociation constant (Kd) and density (Bmax) of 3H-doxazosin binding sites in the canine brain were 0.19 nM and 2.17 fmol/mg wet wt, respectively. The binding of 3H-doxazosin in human prostate homogenates was not consistently linear owing to a relatively high proportion of nonspecific doxazosin binding sites. The mean Kd and Bmax of 3H-doxazosin binding sites in the prostate determined from the saturation experiments yielding linear Scatchard plots were 0.2 nM and 0.51 fmol/mg wet wt. The pharmacology of doxazosin binding sites was further characterized in the canine brain using competitive binding experiments. The rank order of IC50corr values for norepinephrine, clonidine, yohimbine, terazosin, and prazosin indicated that doxazosin binds selectively to alpha 1 and alpha 2 adrenergic binding sites. The relative affinity of unlabeled doxazosin for alpha 1 and alpha 2 binding sites in the human prostate was determined by displacing 125I-Heat or 3H-rauwolscine with varying concentrations of unlabeled doxazosin. The affinity of doxazosin for alpha 1 binding sites in the prostate adenoma was approximately 100-fold greater than its affinity for alpha 2 binding sites. The potency of doxazosin for inhibiting phenylephrine-induced contractions in the prostate indicated that prostate smooth muscle contraction is mediated by alpha 1 adrenoceptors.

Adenoma↗