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P Maurer

Publications and source records attributed to P Maurer.

At least 19 recordsLinked to original sources
PubMed1995

The C-terminal portion of BM-40 (SPARC/osteonectin) is an autonomously folding and crystallisable domain that binds calcium and collagen IV.

The extracellular glycoprotein BM-40 consists of three domains, an acidic domain I, a follistatin (FS)-like domain II and a calcium-binding EC domain with an EF-hand related motif. BM-40 and several other related proteins (QR1, SC1/hevin, testican and tsc-36/FRP) are members of a novel modular protein family that share the FS domain followed by an EC domain. We have expressed this pair of FS and EC domains (mutant delta I) and the calcium-binding EC domain alone (mutant delta I, II) of human BM-40 as recombinant proteins in human 293 cells. Circular dichroism demonstrated that both mutants were obtained as folded proteins with a distinct three-dimensional conformation. In addition, mutant delta I, II could be readily crystallized and diffraction patterns with a resolution limit of 2.4 A resolution were obtained. Calcium binding to this fragment was ten times weaker (Kd = 0.8 microM) than for the wild-type protein. Identical reversible increases in alpha-helicity upon calcium binding were observed for the 150-residue long mutant delta I, II and for BM-40 (286 residues). A 26-residue synthetic peptide corresponding to the EF-hand related motif exhibited much weaker calcium binding. The apparent dissociation constant decreased with increasing peptide concentration (from Kd 2.4 mM at 1 microM, to Kd 0.3 mM at 100 microM peptide concentration) and calcium binding was accompanied by dimerization of the peptide. This suggests that for strong calcium binding the EF-hand related motif has to be embedded into a larger protein domain that can form an autonomously folding protein module. The EC domain was also shown by surface plasmon resonance assay to be responsible for calcium-dependent binding to collagen IV with an affinity (Kd = 19 microM) only sixfold lower than that of intact human BM-40.

Amino Acid Sequence↗
PubMed1995

Preparation and characterization of isozymes and isoforms of horse liver alcohol dehydrogenase.

The procedure described allows the simultaneous large-scale preparation of the three main isozymes (EE, ES, SS) of alcohol dehydrogenase from horse liver (HLADH) and their subfractions using heat denaturation, ammonium sulfate precipitation, DEAE and CM ion-exchange chromatography as well as AMP-Sepharose affinity chromatography. Typical yields that can be obtained within three weeks are 1.5-2.5 g of EE-HLADH, 300-800 mg of ES-HLADH, 20-400 mg of SS-HLADH and 50-100 mg of EE-HLADH isoforms from 5 kg of horse liver. The EE-HLADH isoform prepared has a pI of 7.8, which is 0.3 pH units lower as compared to the main fraction; the zinc content and number of free sulfhydryl groups are unchanged but matrix-assisted laser desorption ionization mass spectrometry resulted in a molecular mass difference of + 130 to 165 relative molecular mass. From a sugar determination and comparison of its pI with an artificial glycosylation product of the EE-HLADH isozyme we concluded that the isoforms of HLADH are non-enzymatic glycosylation products which have been described to occur during protein aging.

Alcohol Dehydrogenase↗
PubMed1995

Actinomyces naeslundii, acute cholecystitis, and carcinoma of the gallbladder.

This report describes the first case of biliary actinomycosis associated with an adenocarcinoma of the gallbladder. Actinomyces naeslundii was encountered as a pure isolate after a precise and careful identification. Although, in diagnosis, cancer and actinomycosis are often confused, the simultaneous occurrence of actinomycosis in cancer lesions can happen. This case illustrates the diagnostic challenge of actinomycosis.

Actinomyces↗
PubMed1994

Changes in calcium and collagen IV binding caused by mutations in the EF hand and other domains of extracellular matrix protein BM-40 (SPARC, osteonectin).

Recombinant expression in a human kidney cell-line was used to prepare mutant human BM-40 with deletions including the N-terminal acidic domain, a central alpha-helical domain and the C-terminal EF hand domain. Two putative EF hand motifs were altered by point mutations. Only elimination of the whole EF hand domain or its single disulfide bond decreased production and secretion indicating that the C-terminal region of BM-40 is essential for correct folding. Deletions in the alpha-helical domain changed a single disulfide bond in this domain and caused oligomerization. Several mutations resulted in significant conformational changes as shown by CD spectroscopy and epitope analysis. Fluorescence titration demonstrated a single high-affinity (Kd = 0.08 microM) calcium-binding site with a low dissociation rate constant. A Glu to Lys mutation in the -Z position of the C-terminal EF hand motif and lack of a stabilizing disulfide bridge caused a 30 to 100-fold reduction in calcium affinity, while an Asp to Lys mutation in the X position had only a small effect. Deletions in the alpha-helical domain caused an even more dramatic reduction in calcium binding and abolished calcium-dependent binding of BM-40 to collagen IV. Both binding properties are critically dependent on a conformational interaction between the EF hand and the alpha-helical domain, which contains the collagen-binding site.

Amino Acid Sequence↗
PubMed1994

Calcium-binding properties of a calcium-dependent protein kinase from Plasmodium falciparum and the significance of individual calcium-binding sites for kinase activation.

Calcium-dependent protein kinase from Plasmodium falciparum (PfCPK) is a multidomain protein composed of an N-terminal kinase domain connected via a linker region to a C-terminal CaM-like calcium-binding domain. The kinase can be activated by Ca2+ alone and associates with 45Ca2+. Here we describe the calcium-binding properties of the kinase and the significance of the individual calcium-binding sites with respect to enzymatic activation, as well as the Ca(2+)-induced conformational change as detected by circular dichroism. As predicted from the cDNA sequence, the kinase has four EF-hand calcium-binding sites in the C-terminal domain. To understand the roles of the individual calcium-binding sites, two series of mutations were generated at the individual EF-hand motifs. The highly conserved glutamic acid residue at position 12 in each calcium-binding loop was mutated to either lysine or glutamine, and therefore a total of eight mutants were generated. Either of these mutations (to lysine or glutamine) is sufficient to eliminate calcium binding at the mutated site. Sites I and II appear to be crucial for both Ca(2+)-induced conformational change and enzymatic activation. Whereas mutations at site II almost completely abolish kinase activity, mutations at site I are also deleterious and dramatically reduce the sensitivity of the Ca(2+)-induced conformational change and the Ca(2+)-dependent activation. Mutations at sites III and IV have minor effects.

Amino Acid Sequence↗
PubMed1994

[Hyperthyroidism].

Hyperthyroidism may result from excessive synthesis for thyroid hormones, from leaking of stored hormones in inflammatory thyroid disease, or from the inappropriate ingestion of thyroid hormones or iodine containing drugs. An overview of the clinical picture and the different types of hyperthyroidism as well as the various approaches used in the diagnostic work-up and in the therapy of hyperthyroidism is presented.

Antithyroid Agents↗
PubMed1994

The integration of alternative treatment modalities in HIV infection--the patient's perspective.

The relationship between professionals representing conventional treatment (CT) and professionals representing non-conventional therapies (alternative therapy (AT) and/or psychotherapy (PT)) is usually characterized by mutual scepticism and mistrust, the overriding fear being that either side will evoke unjustified hopes or will provide false treatment. We investigated whether patients with HIV infection had unrealistic hopes in non-conventional treatment (non-CT), to what extent they use non-CT, and whether perceived benefit and harm differ between the two modes of treatment. We examined a sample of 100 patients with documented HIV-infection in the out-patient department using a self-developed questionnaire, the Hospital Anxiety and Depression Scale (HAD) and data concerning the HIV status. Fifty-six patients used AT and/or PT. Severity of HIV disease did not differ between users and non-users of non-CT. The most important reasons for the use of AT were 'strengthening the body and resistance; supplementing conventional therapy'. Users of non-CT rated the competence of CT lower than non-users in solving medical problems (VAS-scores 0-100: 65.5 +/- 17.6 vs 76.3 +/- 17.7; p = 0.003) and in solving emotional problems (VAS scores 0-100: 35.8 +/- 21.2 vs 48.2 +/- 28.9; p = 0.02). Users of non-CT were significantly more anxious 8.4 +/- 4.8 vs 5.5 +/- 4.6; p = 0.004) and more depressive (5.7 +/- 4.5 vs 3.7 +/- 4.5; p = 0.03) than non-users. Expectations and hopes did not differ between users of AT and non-users: main hopes were a delay of disease progression (76% vs 71%) and an alleviation of symptoms (78% vs 66%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Patent foramen ovale with left to right shunt in bronchopulmonary dysplasia: coincidental or associated complication?

Despite the use of exogenous surfactants, the incidence of bronchopulmonary dysplasia (BPD) has not decreased as much as expected. Of 208 newborns involved in trials with Exosurf at our center, 51 had BPD. Among these newborns, 8 were found retrospectively to have secondary worsening of respiratory distress syndrome after initial improvement with surfactant treatment. Oxygen requirements decreased from 89 +/- 15% to 58 +/- 16% (mean +/- SD), respectively, before and 48 h after surfactant, and then reached a plateau of 34 +/- 10% before dramatic deterioration at 22 +/- 9 days of life. The patients had signs of cardiac failure and increased oxygen requirements of up to 76 +/- 19% within 6 h. A patent foramen ovale (PFO) was demonstrated at echocardiography with a left to right shunt at Doppler. No other cause of worsening was found. Five infants had significant improvement when treated with digoxin and furosemide. This retrospective study raises questions about the relationship between PFO and BPD that should be explored in a prospective study.

Bronchopulmonary Dysplasia↗
PubMed1994

Maternal empathy, family chaos, and the etiology of borderline personality disorder.

Psychoanalytic writers have traced the etiology of borderline personality disorder (BPD) to be a preoedipal disturbance in the mother-child relationship. Despite the prevalence of theories focusing on the role of mothering in the development of BPD, few empirical studies have tested the hypothesis that borderlines were the recipients of unempathic mothering. The current preliminary study compared 13 mothers of borderline adolescents with 13 mothers of normal adolescents. This study found that mothers of borderlines tended to conceive of their children egocentrically, as need-gratifying objects, rather than as individuals with distinct and evolving personalities. This study also found that the mothers of borderlines reported raising their daughters in extremely chaotic families struggling to cope with multiple hardships, including divorce and financial worries. The stressful environmental circumstances reported by the mothers likely affected the borderline daughters directly as well as the mothers' ability to parent effectively and empathically. The results of this study suggest that, as predicted by psychoanalytic theory, a problematic mother-child relationship may play a significant role in the genesis of borderline pathology; however, the life circumstances that contextualize the mother-child relationship also need to be considered when accounting for the etiology of BPD.

Adolescent↗
PubMed1994

Role change after traumatic brain injury in adults.

OBJECTIVES: The purpose of this study was to gather information regarding changes in adult life roles following severe traumatic brain injury. METHOD: The Role Checklist and a semistructured interview were administered to 28 adults with traumatic brain injury who had been in the community for at least 8 months prior to the study. All 28 subjects reported role changes in their lives. RESULTS: The majority of the role changes were losses (71%). More than 64% percent of the subjects reported three or four role losses. The losses were in major organizing roles such as worker, hobbyist, and friend. Most role gains were seen in the roles of home maintainer, family member, and religious participant. Almost 40% of all roles were reported as changed (loss or gain), while more than 60% of roles were reported as unchanged (continuous or absent). The participants' subjective impressions concerning the role changes and why they occurred were elicited. CONCLUSION: With a better understanding of possible role change after traumatic brain injury, rehabilitation professionals can target the development of specific skills necessary for the continuation of valued roles.

Adult↗
PubMed1993

The flow-volume loop in bilateral vocal cord paralysis.

A 38-year-old man with posttraumatic bilateral vocal cord paralysis and a surgically repaired avulsion of the extrathoracic trachea presented with a slight increase of exertional dyspnea (grade 2). Spirometry showed high normal FEV1 for FVC variables, but the F-V loop was characteristic for highly variable UAO with an increased FEV1/PEF ratio of 11 ml/L/min as well as a MEF50/MIF50 of 4.55. Endoscopy during forced respiration showed near total inspiratory obstruction of the larynx due to paradoxical behavior of the vocal cords. In extrathoracic airway obstruction a FEV1/PEF ratio > 10 ml/L/min combined with a MEF50/MIF50 ratio > 4 is suggestive of variable UAO caused by bilateral vocal cord paralysis rather than by a tracheal lesion.

Adult↗
PubMed1992

High-affinity and low-affinity calcium binding and stability of the multidomain extracellular 40-kDa basement membrane glycoprotein (BM-40/SPARC/osteonectin).

Reversible binding of calcium ions to a single high-affinity binding site in the 40-kDa basement membrane protein (BM-40) caused a 33% increase of alpha-helicity, an about 60% change in intrinsic fluorescence and a dramatic increase of the rate of cleavage by alpha-chymotrypsin. All these effects exhibited identical dependencies on calcium concentration from which a dissociation constant Kd = 0.6 microM was determined. Calcium release was accompanied by an increase of the frictional ratio in solution but not by denaturation which occurred at about equal guanidine.HCl concentration for both calcium-saturated and calcium-depleted protein (midpoint 1.5 M). The cleavage sites for alpha-chymotrypsin are located in or near to the EF-hand domain IV of calcium-depleted BM-40 (also known as SPARC, i.e. secreted protein acidic and rich in cysteine, and osteonectin). These and other data indicate that binding occurs in the EF-hand domain from which a large conformational change is transmitted. Low-affinity calcium-binding sites in the N-terminal glutamic-acid-rich domain I of BM-40 were identified by human leukocyte elastase which was found to cleave very specifically in the middle of this domain. From the increase of cleavage rate with increasing calcium concentration a Kd greater than or equal to 10 mM was estimated. It is suggested that variations of calcium levels in the extracellular space in this range may regulate functions of BM-40 such as collagen binding and that high-affinity binding is important for stabilization, folding and secretion during biosynthesis.

Amino Acid Sequence↗
PubMed1991

Substrate specificity and stereoselectivity of horse liver alcohol dehydrogenase. Kinetic evaluation of binding and activation parameters controlling the catalytic cycles of unbranched, acyclic secondary alcohols and ketones as substrates of the native and active-site-specific Co(II)-substituted enzyme.

1. The steady-state parameters kcat and Km and the rate constants of hydride transfer for the substrates isopropanol/acetone; (S)-2-butanol, (R)-2-butanol/2-butanone; (S)-2-pentanol, (R)-2-pentanol/2-pentanone; 3-pentanol/3-pentanone; (S)-2-octanol and (R)-2-octanol have been determined for the native Zn(II)-containing horse-liver alcohol dehydrogenase (LADH) and the specific active-site-substituted Co(II)LADH. 2. A combined evaluation of steady-state kinetic data and rate constants obtained from stopped-flow measurements, allowed the determination of all rate constants of the following ordered bi-bi mechanism: E in equilibrium E.NAD in equilibrium E.NAD.R1R2 CHOH in equilibrium E.NADH.R1R2CO in equilibrium E.NADH in equilibrium E. 3. On the basis of the different substrate specificities of LADH and yeast alcohol dehydrogenase (YADH), a procedure has been developed to evaluate the enantiomeric product composition of ketone reductions. 2-Butanone and 2-pentanone reductions revealed (S)-2-butanol (86%) and (S)-2-pentanol (95%) as the major products. 4. The observed enantioselectivity implies the existence of two productive ternary complexes; E.NADH.(pro-S) 2-butanone and E.NADH.(pro-R) 2-butanone. All rate constants describing the kinetic pathways of the system (S)-2-butanol, (R)-2-butanol/2-butanone have been determined. These data have been used to estimate the expected enantiomer product composition of 2-butanone reductions using apparent kcat/Km values for the two different ternary-complex configurations of 2-butanone. Additionally, these data have been used for computer simulations of the corresponding reaction cycles. Calculated, simulated and experimental data were found to be in good agreement. Thus, the system (S)-2-butanol, (R)-2-butanol/2-butanone is the first example of a LADH-catalyzed reaction for which the stereochemical course could be described in terms of rate constants of the underlying mechanism. 5. The effects of Co(II) substitution on the different steps of the kinetic pathway have been investigated. The free energy of activation is higher for alcohol oxidation and lower for ketone reduction when catalyzed by Co(II)LADH in comparison to Zn(II)LADH. However, the free energies of binding are affected by metal substitution in such a way that the enantioselectivity of ketone reduction is not significantly changed by the substitution of Co(II) for Zn(II). 6. Evaluation of the data shows that substrate specificity and stereoselectivity result from combination of the free energies of binding and activation, with differences in binding energies as the dominating factors. In this regard, the interactions of substrate molecules with the protein moiety are dominant over the interactions with the catalytic metal ion.

Alcohol Dehydrogenase↗
PubMed1991

Risk factors for adverse drug reactions communication of the CHDM.

In the CHDM (Comprehensive Hospital Drug Monitoring for Adverse Drug Reactions, Bern/St. Gallen), the data of the 34,838 computer registered patient admissions 1974-1988 were available for evaluation. We summarize the results of three different studies: 1. A multivariate analysis of the risk factors to developed an ADR during hospital stay, mainly the number of drugs, age, sex and renal function. 2. The occurrence rate of hyperkalemia under the treatment with diurectics, mainly potassium (K+)-losing with K+ substitution compared to the combination of K(+)-sparing with K(+)-losing preparations. 3. The occurrence-rate of exanthema in relation to amino-penicillin preparations an allopurinol. The results are presented in the communication. (Tab 7, Fig. 1, Ref. 15). Ref. 15.).

Adverse Drug Reaction Reporting Systems↗
PubMed1990

[Hyperkalemia with potassium-sparing and potassium-losing diuretics. Results from the Comprehensive Hospital Drug Monitoring Bern (CHDM)].

Of 5047 in-patients in the Division of Internal Medicine, Zieglerspital Bern (regional/teaching hospital), admitted from 1982 to 1985, 2412 were treated with at least one diuretic. The hospital records of these patients were reviewed with regard in particular to serum potassium and creatinine values as well as potassium supplementation. On the basis of this evaluation the patients were assigned to 6 different treatment groups and the relative occurrence rate of hyperkalemia probably related to drug treatment was determined. Of the 590 patients treated with only potassium losing diuretics, none was found to show a hyperkalemia event; of the 742 patients on potassium losing diuretics and potassium supplementation, 27 (3.6%) developed hyperkalemia. In the 439 patients under combined diuretics (potassium sparing with potassium losing) without potassium substitution, 76 (17.3%), and in the 381 under combined diuretics with potassium substitution 24 (6.3%), developed hyperkalemia. The further groups of patients are also described. Renal function was estimated by the formula of Cockcroft and Gault. Reduced renal function is a significant risk-factor for hyperkalemic events under combined diuretics. All hyperkalemic events were within a serum potassium range of 5.1-7.0 mmol/l.

Creatinine↗
PubMed1990

Risk of acute upper gastrointestinal bleeding in patients with ulcerative disease and treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Results from the Comprehensive Hospital Drug Monitoring Berne (CHDM).

The hospital prevalence rate for upper gastrointestinal ulcerative disease in 28,531 inpatients consecutively admitted in two teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM) in Berne, from 1974 to 1985, was 2.2% (1.8% for gastric or duodenal ulcer, and 0.4% for erosive gastritis). This was based on the evaluation of 634 patients after exclusion of the subgroup of patients with hepatic cirrhosis or upper gastrointestinal neoplasia. After exclusion of patients on anticoagulant therapy (n = 73), 561 (= 100%) patients could be further studied. Of them, 33.3% (n = 187) were found to have been exposed to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, within 21 days prior to confirmation of the diagnosis. The observed relative risk (RR) of developing a substantial acute upper gastrointestinal bleeding (Hb less than 10 g/100 ml for men, and less than 9 g/100 ml for women, or a decrease in Hb of more than 25%) was 1.61 when patients exposed to NSAIDs (n = 187) were compared to patients not exposed to those drugs (n = 374). Although there was no significant sex difference overall, the RR for gastrointestinal bleeding differed considerably in the various age-groups; it was elevated in men under 40 years (RR = 2.86) and in women over 60 years of age (RR = 1.89), as compared to the mean RR of 1.61.

Adult↗
PubMed1990

Mastocytosis and atopy: a study of 33 patients with urticaria pigmentosa.

Thirty-three patients with histologically verified urticaria pigmentosa were studied for coexisting atopic disease by means of history, skin prick testing with five common inhalants and serological investigation for total IgE and specific IgE antibodies to five common inhalants. The prevalence of atopy in urticaria pigmentosa was similar to that observed in the normal Swiss population, both on the basis of history (7/33 = 21%) and of positive skin prick tests to common inhalants (12/33 = 36%). However, total serum IgE levels were significantly lower (geometric mean value 16.8 kU/l) than in a control group of 52 Swiss blood donors of comparable age and sex distribution (geometric mean value 43.0 kU/l, t = 2.93, P less than 0.005). Specific IgE antibodies to common inhalants were also observed less frequently in urticaria pigmentosa patients than in controls, although this difference was not statistically significant. Low total and specific IgE values in patients with urticaria pigmentosa may be explained by increased absorption of circulating IgE to abundant tissue mast cells.

Adolescent↗