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Biomedical subjects

M Scharf

Publications and source records attributed to M Scharf.

At least 19 recordsLinked to original sources
PubMed2005

[Sonography of the optical nerve -- experience in 483 children].

INTRODUCTION: In case of increased intracranial pressure (IICP), the inflow of cerebrospinal fluid widens the space between the optic nerve (ON) itself and the surrounding dura mater leading to the sonographic appearance of increased diameter of the ON. The purpose of the study was to gain clinical experience in children and to determine (a) the mean values for patients without proven IICP and (b) pathologic values of those with proven IICP. MATERIALS AND METHODS: Ultrasound of the optic nerve was performed in 483 children with symptoms consistent with IICP, comprising 287 males and 196 females at an age ranging from 4 days to 24 years with a mean age of 7.5 + 5.1 years. The measured diameter of the ON of both eyes and the morphologic criteria concerning nerve sheath and papilla were evaluated retrospectively. RESULTS: Most of the investigated patients (n = 466) had no IICP as confirmed by neurological examination, EEG, sometimes CCT and/or MRI and clinical follow-up. The typical morphological findings in patients with normal intracranial pressure (ICP) were a clear and longitudinally extended demarcation of the ON with a well-delimited nerve sheath and without prominent papilla. The mean diameter of the ON in patients with normal ICP was 3.4 mm + 0.7 mm. In 17 patients with proven IICP, the mean diameter of the ON increased to 5.6 mm + 0.9 mm. Typically, the nerve sheath was indistinguishable from the hypoechoic ON, often but not invariably associated with a prominent papilla. In patients with IICP, the diameter of the ON alone matches the diameter of the ON plus nerve sheath in patients with normal ICP. CONCLUSION: IICP was detected with a high sensitivity by ultrasound using the diameter and the morphological criteria of an indistinguishable nerve sheath. A diameter of more than 4.5 mm is definitely pathologic and requires further investigation. Prominence of the papilla is an unreliable criterion for acute IICP.

Adolescent↗
PubMed2002

Differential expression and induction of two Drosophila cytochrome P450 genes near the Rst(2)DDT locus.

Previous studies have shown that the major metabolic resistance locus in the insecticide-resistant Drosophila line Rst(2)DDT(Wisconsin) maps between the markers cn and vg on chromosome 2. Six cytochrome P450 genes exist in this region. We investigated the expression levels of these P450 genes in DDT-resistant and -susceptible fly lines. We report: (i) DDT resistance is significant (> 30-fold) and dominant, (ii) resistance is reduced by the cytochrome P450 inhibitor PBO, (iii) there is constitutive over-expression relative to susceptible flies of two genes encoding cytochrome P450 enzymes within the cn-vg region (CYP6G1 = 4.3-fold; CYP12D1 = 6.0-fold), and (iv) exposure to DDT results in an increased expression of only one of these two P450 genes (CYP12D1 > or = 6-fold above constitutive resistant fly baselines).

Animals↗
PubMed2001

The capacity for romantic intimacy: exploring the contribution of best friend and marital and parental relationships.

This study examined, in a longitudinal design, the contributions of three different relationships, namely marital, parent-child and best friend, to the capacity for intimacy in romantic relationships of Israeli male adolescents, as well as the mediating role of socio-emotional capacities. Eighty-four 17-year-old adolescents and their parents filled out questionnaires concerning the quality of these relational contexts. Four years later the Intimacy Status Interview was administered to the adolescents at the conclusion of their mandatory military service to examine closeness, separateness, and commitment within their romantic relationships. Results showed that all relational contexts were related to capacity for intimacy (directly or indirectly), with higher relational qualities associated with better capability for intimacy. The marital relationship was associated with intimacy through its effect on the parent-child relationships. The effects of the parent-child relationships on the capacity for intimacy were mediated through the adolescents' socio-emotional capabilities. The contribution of the parent-adolescent relationships to the capacity for closeness and commitment was further mediated through relationships with the best friend, whereas the contribution to the capacity for separateness was not. A substantial number of our participants showed high capability for intimacy although in the military service context the circumstances for the development of intimacy were quite limited and non-optimal. Exploration of the separateness and closeness facets of intimacy in romantic relationships in the two sexes and in other contexts is recommended.

Adolescent↗
PubMed2001

Parental divorce and young adult children's romantic relationships: resolution of the divorce experience.

Fifty-one romantically involved young Israeli adults, whose parents were divorced, were questioned about their romantic relationship, parents' conflict, and current feelings about and reconstruction of the divorce. An integrative perception of the divorce was found to be related to fewer problems and to higher levels of friendship, enjoyment, and intimacy in the relationship. Implications for research and intervention with young adults are discussed.

Adult↗
PubMed2001

Radiobiological hypoxia, oxygen tension, interstitial fluid pressure and relative viable tumour area in two human squamous cell carcinomas in nude mice during fractionated radiotherapy.

Very little is known about the correlation between the radiobiological hypoxic fraction (rHF) and other measures of tumour oxygenation during fractionated irradiation. In the present study the rHF is determined in untreated human FaDu and GL squamous cell carcinoma in nude mice and in tumours irradiated with 10 fractions in 2 weeks and 20 fractions in 4 weeks, using tumour control as the experimental endpoint. The results were compared with measurements of the pO2, the interstitial fluid pressure (IFP) and the relative viable tumour area. In FaDu tumours the radiobiological hypoxic fractions (rHFs) before and during irradiation were not statistically different from 100%. Depending on the assumptions made for D0, the rHFs of GL tumours were between 0.2 and 4% or 30 and 53%. The median pO2 values were 2.8 mmHg for untreated FaDu tumours and 0.2 mmHg for GL tumours (p < 0.001). The median IFP values were 2.6 mmHg in FaDu and 5.3 mmHg in GL tumours (p = 0.01). No important changes in the pO2 and IFP values were observed during fractionated irradiation. The relative viable tumour area during irradiation decreased by 83% in FaDu tumours (p = 0.002) and by 54% in GL tumours (p = 0.003). It is concluded that differences in rHF exist between FaDu and GL tumours before and during fractionated irradiation and that these differences are not reflected by pO2 and IFP values and the relative viable tumour area.

Animals↗
PubMed2000

Eight weeks of non-nightly use of zolpidem for primary insomnia.

CONTEXT: Intermittent use (i.e., a few nights per week) of hypnotic medication is often recommended for the treatment of chronic insomnia despite an absence of efficacy and safety data using this regimen. STUDY OBJECTIVES: To evaluate the clinical efficacy and safety of intermittent pharmacotherapy for chronic insomnia. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, parallel groups, clinical trial at six sleep research sites. PATIENTS: One hundred-sixty-three (115 women, 48 men; mean age 44.1+ SE. 0.9 years), DSM-IV-defined primary insomnia patients were randomized, 134 patients completed the study. INTERVENTIONS: Eight weeks of treatment with either zolpidem 10 mg or placebo. Patients were instructed to take medication when they felt they needed it, but at least three and no more than five times per week. MAIN OUTCOME MEASURES: Investigator and Patient Global Ratings were the primary outcome variables. Secondary measures from daily questionnaires to assess efficacy, rebound insomnia and drug taking behavior. RESULTS: The Investigator's Global Rating indicated that intermittent use of zolpidem produced a significantly better therapeutic effect and significantly reduced insomnia severity throughout the 8-week study relative to placebo. Zolpidem was found to be effective in initiating and maintaining sleep on nights taken, as compared to placebo, based upon the Patient's Global Ratings and all subjective sleep variables. No evidence of rebound insomnia was found on nights that zolpidem was not taken. The number of nights a pill was taken did not differ between groups, nor did frequency of pill taking change in either group across the duration of the study. There were no significant effects of treatment upon quality of life or neurocognitive measures. CONCLUSIONS: Zolpidem 10 mg is effective in treating insomnia when used intermittently, without evidence of discontinuation effects or increased frequency of pill taking.

Analysis of Variance↗
PubMed2000

A five week, polysomnographic assessment of zaleplon 10 mg for the treatment of primary insomnia.

Objective: To examine the hypnotic efficacy of zaleplon 10 mg, a selective benzodiazepine receptor agonist, over a period of 35 nights in primary insomniacs.Methods: A double-blind, parallel-group, placebo-controlled design was employed. Subjects were 113 men and women, ages 18 to 65 years. Polysomnographic and subjective sleep data were collected during baseline, on two nights during each of five treatment weeks, and on the first two nights after discontinuation of active medication.Results: Sleep latency was significantly shortened with zaleplon 10 mg for all 5 weeks of treatment as assessed by polysomnography and by subjective sleep measures. Total sleep time, whether evaluated with polysomnography or with subjective estimates, was inconsistently affected. Sleep architecture was similar with zaleplon and placebo. There was no evidence of tolerance to the sleep promoting effects of zaleplon during the five weeks of administration, and there was no rebound insomnia upon discontinuation. Adverse events occurred with equal frequency in the zaleplon and placebo groups.Conclusions: Zaleplon 10 mg is effective in the treatment of sleep onset insomnia over a period of 35 nights, with minimal evidence of undesired effects.

Journal Article↗
PubMed2000

Loratadine versus cetirizine: assessment of somnolence and motivation during the workday.

OBJECTIVE: This parallel-group, double-blind study compared the somnolence and motivation profiles of 2 second-generation antihistamines, loratadine and cetirizine, in patients with allergic rhinitis. BACKGROUND: Second-generation antihistamines were developed to provide symptomatic relief from allergic disorders without the unwanted side effects of first-generation antihistamines, including somnolence. Recent research has indicated that not all second-generation antihistamines are comparable with respect to somnolence and other cognitive processes. METHODS: Patients aged > or = 12 years and actively exhibiting symptoms of allergic rhinitis were randomized to 2 treatment groups to receive 10 mg loratadine or 10 mg cetirizine daily at 8:00 AM for 1 week. After patients took the medication, their somnolence and degree of motivation to perform activities were recorded in an electronic diary using a visual analog scale 4 times during the workday (8:00 AM, 10:00 AM, noon, and 3:00 PM). RESULTS: Sixty patients (31 men, 29 women) were randomized to treatment. Somnolence scores were similar for both groups at baseline and at the time of dosing (8:00 AM). However, there was a statistically significant difference in somnolence scores between the loratadine and cetirizine groups at 10:00 AM (P = 0.008), noon (P = 0.001), and 3:00 PM (P < 0.001), with the cetirizine group showing a greater degree of somnolence. The scores on motivation to perform activities were similar for both groups at the baseline and 8:00-AM measurements. In parallel with the somnolence scores, there were statistically significant differences in motivation scores between the loratadine and cetirizine groups at 10:00 AM (P = 0.014), noon (P = 0.001), and 3:00 PM (P < 0.001), indicating that patients taking loratadine were relatively more motivated during the workday. CONCLUSION: The results of this study demonstrate that in patients aged > or = 12 years who had allergic rhinitis, cetirizine use promoted somnolence and decreased motivation to perform activities during the workday compared with loratadine.

Adult↗
PubMed2000

Family relationships, leaving home, and adjustment to military service.

Associations between family relationships and individual adjustment were studied within a sample of 19-year-old soldiers during their first weeks of basic training. Results showed that family relationships partly explained soldiers' closeness to best friends, number of social nominations, and commanders' ratings of soldiers' military and social competence. In addition, family relations explained soldiers' perceived social competence as assessed via closeness to best friends and number of sociometric nominations. Together, the results reiterate the role played by the family and attitudes toward offspring leaving home and toward their adjustment to military service.

Adult↗
PubMed2000

Zaleplon improves sleep without producing rebound effects in outpatients with insomnia. Zaleplon Clinical Study Group.

The efficacy and safety of three doses of zaleplon, a novel non-benzodiazepine hypnotic, were compared with those of placebo in outpatients with insomnia in this 4-week study, using zolpidem 10 mg as active comparator. Postsleep questionnaires were used to determine treatment effects on the patient's perception of sleep, as well as any development of pharmacological tolerance during therapy or rebound insomnia or withdrawal symptoms upon discontinuation of therapy. During week 1, sleep latency was significantly shorter with zaleplon 5, 10, and 20 mg compared to placebo. The significant decrease in sleep latency persisted through week 4 with zaleplon 20 mg, and was again evident with zaleplon 10 mg at week 3. Zaleplon 20 mg also had significant effects on sleep duration, number of awakenings, and sleep quality compared to placebo. No pharmacological tolerance developed during treatment with zaleplon and there were no indications of rebound insomnia or withdrawal symptoms after treatment discontinuation. Zolpidem 10 mg had significant effects on sleep latency, sleep duration, and sleep quality compared to placebo. However, a significantly greater incidence of withdrawal symptoms and a suggestion of sleep difficulty after treatment discontinuation (rebound insomnia) for all sleep measures was seen with zolpidem compared to placebo. There was no significant difference in the frequency of adverse events with active treatment compared to placebo. These results show that zaleplon provides effective treatment of insomnia with a favourable safety profile.

Acetamides↗
PubMed2000

Close relationships and social competence of hospitalized and nonhospitalized adolescents.

This study was designed to examine the social relationships of adolescents with severe disorders. The study sample consisted of 33 adolescent inpatients in a psychiatric unit, as well as 33 nonhospitalized adolescents. Participants completed the Network of Relationship Inventory for an assessment of the quality of their relationships with mother, father, close friend, and other significant adults. In addition, friendship intimacy was assessed. Results showed nonhospitalized adolescents describing a close relationship with their parents, as well as with their close friends. Their relationships with their friends were mature. Hospitalized adolescents described a less close relationship with their parents, whereas they were close to and valued their relationships with their friends and other significant adults. Though both groups described similar levels of emotional closeness, hospitalized adolescents tended more to exert control or to evince a penchant for similarity to the other in their friendships. Results are discussed within the framework of adolescent social tasks.

Adolescent↗
PubMed1998

Structure and dynamic properties of the single disulfide-deficient alpha-amylase inhibitor [C45A/C73A]tendamistat: an NMR study.

Covalent linkages such as disulfide bonds are important for the stabilization of proteins. In the present NMR study we compare the structure and the dynamics of the single disulfide-deficient variant C45A/C73A of the alpha-amylase inhibitor tendamistat and the wild-type protein, which contains two disulfide bonds (C11-C27 and C45-C73). Complete proton assignment was achieved by standard homonuclear 2D techniques for the variant. Chemical shift differences, intra-strand NOE effects and protected amide proton were used to compare the connectivity of the secondary structure elements of variant and wild-type. Dynamic properties of the wild-type protein were studied by 13C(alpha) heteronuclear NOE experiments with carbon in natural abundance. 15N isotope labeling was necessary to obtain the relaxation parameters of the variant, because of sample degradation. The 15N resonance assignment was achieved by a 15N 3D-NOESY-HMQC. Removal of the C45-C73 bond by the C45A/C73A mutation has no influence upon the beta-barrel structure of tendamistat beside very local changes at the mutation site. The relaxation data revealed only subtle differences between variant and wild-type on a subnanosecond time scale. Only the N-terminus and G62 in the connecting loop between the anti-parallel beta-sheets showed an increased mobility. The results are discussed in respect to thermodynamic stability and the secretion efficiency of tendamistat.

Disulfides↗
PubMed1997

Effect of preformed correct tertiary interactions on rapid two-state tendamistat folding: evidence for hairpins as initiation sites for beta-sheet formation.

The role of preformed correct side chain interactions, such as disulfide bonds, on protein folding kinetics is still not well understood. We investigated the effect of disulfide bond replacements on folding and stability of the small beta-sheet protein tendamistat. Tendamistat folds very fast (tau = 10 ms at pH 7 in water) and without detectable intermediates, which facilitates molecular interpretation of the kinetic data. Tendamistat contains two disulfide bonds, one between cysteines 11 and 27, which connects the ends of a beta-hairpin, and a second one between cysteines 45 and 73, which brings together the two outer strands of a three-stranded beta-sheet. Two single-disulfide variants of the protein were prepared by site-directed mutagenesis (tendamistat C11A/C27S and tendamistat C45A/C73A), and the effects on stability and on folding were monitored. Replacement of either disulfide bond leads to a large decrease in protein stability (DeltaDeltaG0 = 6.0 kcal/mol for the C11A/C27S variant and 5.1 kcal/mol for the C45A/C73A variant). This effect is caused both by entropic stabilization of the unfolded state and by enthalpic destabilization of the native structure. Kinetic experiments show that the main effect of fixed side chain contacts is on the unfolding rate. For both single-disulfide variants, unfolding is strongly accelerated (4250 times in the C11A/C27S variant and 250 times in the C45A/C73A variant) whereas the refolding rate constants are only slightly decreased. The activation parameters show that the observed small effect on the refolding reaction in the C11A/C27S variant is a consequence of large and compensating changes in the entropy and enthalpy of activation. Structural interpretation of the kinetic data suggests that formation of the beta-hairpin stabilized by the C11-C27 disulfide bond forms in the rate-limiting step of the refolding process. The interactions between the outer strands of the beta-sheet connected by the C45-C73 disulfide bond, in contrast, are made late in refolding. These results support the idea that beta-hairpins are initiation sites for beta-sheet formation and that additional strands are added late in the folding process.

Disulfides↗
PubMed1997

Effect of beta-carboline-3-carboxoylate-t-butyl ester on ventilatory control.

beta-carboline-3-carboxylate-t-butyl ester (beta CCT) is the most selective antagonist for the alpha 1 beta 2 gamma 2 benzodiazepine (BZ) receptor subtype which blocks anticonvulsant and antipunishment (anxiolytic) but not sedative and myorelaxant effects of diazepam. We sought to determine whether the alpha 1 beta 2 gamma 2 BZ receptor subtype modulates ventilation and whether beta CCT antagonizes respiratory depressant effects of BZ's. Room air (RA) ventilation and the ventilatory response to 6% & 12% CO2 were non-invasively assessed by barometric plethysmography in 30 gm mice, n = 11. Plethysmograph signal amplitude (AMP), respiratory rate (RR) and minute ventilatory effort (MVE = AMP*RR), were measured. Runs were performed pre-drug & after IP injection of saline, vehicle for beta CCT, beta CCT (60mg/kg), midazolam (10mg/kg), and midazolam followed by beta CCT. Compared with pre-drug value, midazolam depressed MVE during RA and CO2 stimulation (% of pre-drug value: RA:57.7 +/- 17.4%, 6% CO2:53.73 +/- 14.3%, 12% CO2:69.1 +/- 26.1%, p < .0001, ANOVA). Subsequent beta CCT partially reversed this depression during RA conditions (72.8 +/- 25.7% of pre-drug value, p < .03 compared with midazolam) and 6% CO2 stimulation (67.1 +/- 10.7% of pre-drug value, p < .006 compared with midazolam) but not with 12% CO2. Thus, the alpha 1 beta 2 gamma 2 BZ receptor subtype modulates ventilation and beta CCT partially antagonizes respiratory depressant effects of BZ's.

Animals↗
PubMed1996

The PDBFINDER database: a summary of PDB, DSSP and HSSP information with added value.

MOTIVATION: The Protein Data Bank currently contains more than 4700 protein coordinate sets. It is often desirable to make a selection from these files based on a criterion like R-factor, experimental method, length of the amino acid sequence, or the number of homologous sequences in SWISSPROT. Doing this using the distributed form of the Protein Data Bank can be a tedious task, because (1) this requires reading one file for every single entry, and (2) not all of the information is present in a consistent computer readable way in all of the entries. RESULTS: The PDBFINDER database provides an easy to interpret file containing summary information about all Protein Data Bank files. Summary information from the DSSP (Definition of Secondary Structure of Proteins) and HSSP (Homology derived Secondary Structure of Proteins) databases is also included. Furthermore, where essential data were missing from the Protein Data Bank file, this information has been retrieved from the original literature. AVAILABILITY: The latest version of the PDBFINDER database can be downloaded by anonymous ftp from swift.embl-heidelberg.de, directory:/pdbfinder. CONTACT: E-mail address hooft@embl-heidelberg.de.

Amino Acid Sequence↗
PubMed1995

Mechanism of protein stabilization by disulfide bridges: calorimetric unfolding studies on disulfide-deficient mutants of the alpha-amylase inhibitor tendamistat.

The present differential scanning calorimetry and circular dichroism studies on the mechanism of protein stabilization by disulfide bonds were concerned with two questions: is the increase in unfolding entropy upon removal of disulfide links sufficient for the explantation of the general stability decrease of disulfide-deficient mutants? Is it immaterial by which residue cysteine residues are replaced when disulfide bridges are to be opened? To answer these questions we investigated two disulfide bridge mutants of the alpha-amylase inhibitor Tendamistat where the large loop (C45A/C73A) or the small loop (C11A/C27A) had been opened by recombinant DNA techniques, and we compared the stability of the mutated proteins with that of wild-type Tendamistat published previously. To elucidate the significance of the nature of the group that replaces Cys we introduced in position 27 of the small loop four different amino acids instead of Cys: Ala, Leu, Ser and Thr. Surprisingly, opening of the small loop (17 residues) causes larger destabilization than opening of the large loop comprising 29 residues. The thermodynamic parameters at pH 7.0 are: wild-type: t1/2 = 81.6 degrees C, delta Hcal = 296 kJ mol-1, large loop mutant (C45A/C73A): t1/2 = 58.6 degrees C, delta Hcal = 225 kJ mol-1 and small loop mutant (C11A/C27A): t1/2 = 42.7 degrees C, delta Hcal = 135 kJ mol-1. This finding is at variance with the entropy hypothesis. The relative contributions to stability of enthalpic and entropic terms can be varied by a proper choice of substitutions. While the destabilization originating from C45A/C73A exchanges in the large loop turns out to be purely entropic, the stability decreases of the small loop mutants are caused by changes in both enthalpic and entropic terms. Leu or Ser in position 27 leads to an overall enthalpic destabilization. Thr in position 27 increases the transition enthalpy of this mutant to the value of the wild-type protein but increases at the same time the value of the transition entropy with the result of an overall entropic destabilization. Finally, in the C11A/C27A small loop mutant of lowest stability a very large enthalpic destabilization occurs, which is, however, partly counterbalanced by a reduction in the transition entropy. The preferential perturbation of the native state by the mutations is manifest in the increase of the native state heat capacity relative to that of the wild-type protein and the identity of the heat capacity of the unfolded state.(ABSTRACT TRUNCATED AT 400 WORDS)

Calorimetry, Differential Scanning↗
PubMed1995

Electrochemical studies on nitrite reductase towards a biosensor.

A c-type hexaheme nitrite reductase (NiR) isolated from nitrate-grown cells of Desulfovibrio desulfuricans (Dd) ATCC 27774 catalyses the six-electron reduction of nitrite to ammonia. Previous electrochemical studies demonstrated that a simple electrocatalytic mechanism can be applied to this system (Moreno, C., Costa, C., Moura, I., LeGall, J., Liu, M. Y., Payne, W. J., Van Dijk, C. and Moura, J. J. G. (1992) Eur.J.Biochem. 212, 79-86). Its substrate specificity, availability and stability under ambient conditions makes this enzymatic system a promising candidate for use in a biosensor device. An electrochemical study of gel-immobilized Dd NiR on a glassy carbon electrode revealed both enzymatic activity and amperometric response to nitrite. In this study it was observed that the catalytic current density is a function of the nitrite concentration in solution and follows a characteristic Michaelis-Menten-type substrate dependence. Such a biosensor device (NiR-electrode) bears the option to be used for analytical determination of nitrite in complex media.

Biosensing Techniques↗