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Biomedical subjects

M Frank

Publications and source records attributed to M Frank.

At least 37 records · Page 2Linked to original sources
PubMed2001

Differential conformational requirements for activation of G proteins and the regulatory proteins arrestin and G protein-coupled receptor kinase in the G protein-coupled receptor for parathyroid hormone (PTH)/PTH-related protein.

After stimulation with agonist, G protein-coupled receptors (GPCRs) activate G proteins and become phosphorylated by G protein-coupled receptor kinases (GRKs), and most of them translocate cytosolic arrestin proteins to the cytoplasmic membrane. Agonist-activated GPCRs are specifically phosphorylated by GRKs and are targeted for endocytosis by arrestin proteins, suggesting a connection between GPCR conformational changes and interaction with GRKs and arrestins. Previously, we showed that by substitution of histidine for residues at the cytoplasmic side of helix 3 (H3) and helix 6 (H6) of the parathyroid hormone (PTH) receptor (PTHR), a zinc metal ion-binding site is engineered that prevents PTH-stimulated G(s) activation (Sheikh, S. P., Vilardaga, J.-P., Baranski, T. J., Lichtarge, O., Iiri, T., Meng, E. C., Nissenson, R. A., and Bourne, H. R. (1999) J. Biol. Chem. 274, 17033-17041). These data suggest that relative movements between H3 and H6 are critical for G(s) activation. Does this molecular event play a similar role in activation of GRK and arrestin and in PTHR-mediated G(q) activation? To answer this question, we utilized the two previously described mutant forms of PTHR, H401 and H402, which contain a naturally present histidine residue at position 301 in H3 and a second substituted histidine residue at positions 401 and 402 in H6, respectively. Both mutant receptors showed inhibition of PTH-stimulated inositol phosphate and cAMP generation in the presence of increasing concentrations of Zn(II). However, the mutants showed no Zn(II)-dependent impairment of phosphorylation by GRK-2. Likewise, the mutants were indistinguishable from wild-type PTHR in the ability to translocate beta-arrestins/green fluorescent protein to the cell membrane and were also not affected by sensitivity to Zn(II). These results suggest that agonist-mediated phosphorylation and internalization of PTHR require conformational switches of the receptor distinct from the cAMP and inositol phosphate signaling state. Furthermore, PTHR sequestration does not appear to require G protein activation.

Animals↗
PubMed2001

Discrimination between bacterial spore types using time-of-flight mass spectrometry and matrix-free infrared laser desorption and ionization.

We demonstrate that molecular ions with mass-to-charge ratios (m/z) ranging from a few hundred to 19 050 can be desorbed from whole bacterial spores using infrared laser desorption and no chemical matrix. We have measured the mass of these ions using time-of-flight mass spectrometry and we observe that different ions are desorbed from spores of Bacillus cereus, Bacillus thuringiensis, Bacillus subtilis, and Bacillus niger. Our results raise the possibility of identifying microorganisms using mass spectrometry without conventional sample preparation techniques such as the addition of a matrix. We have measured the dependence of the ion yield from B. subtilis on desorption wavelength over the range 3.05-3.8 microm, and we observe the best results at 3.05 microm. We have also generated mass spectra from whole spores using 337-nm ultraviolet laser desorption, and we find that these spectra are inferior to spectra generated with infrared desorption. Since aerosol analysis is a natural application for matrix-free desorption, we have measured mass spectra from materials such as ragweed pollen and road dust that are likely to form a background to microbial aerosols. We find that these materials are readily differentiated from bacterial spores.

Bacillus↗
PubMed2001

Evaluation of manual-based cognitive-behavioral therapy for bulimia nervosa in a service setting.

In the present study manual-based cognitive-behavioral therapy for bulimia nervosa was evaluated on an unselected sample of an out-patient service facility. A total of 73 female patients who asked for treatment received the primary diagnosis of bulimia nervosa. Of these, 67 took up treatment. Treatment was completed by 66 patients. Outcome variables were the number of binge episodes along with questionnaire scores for restraint eating, emotional eating, body dissatisfaction and depressiveness. At the end of treatment and 1 year after the end of treatment significant improvements were found in all outcome variables. Effect sizes for outcome variables were within the range of those of controlled research. Therefore, the present study delivered empirical evidence that manual-based cognitive-behavioral therapy is an effective treatment for bulimia nervosa not only within the restricted area of research.

Adolescent↗
PubMed2001

Short- and long-term effectiveness of an empirically supported treatment for agoraphobia.

This study examined the effectiveness of individual high-density exposure (2-3 weeks, all day) for panic disorder with agoraphobia (PDAG). Participants were 416 unselected patients with a primary diagnosis of PDAG who were treated by 52 therapists in 3 outpatient clinics of the Christoph-Dornier Foundation of Clinical Psychology in Germany. Results 6 weeks after the end of therapy and at the 1-year follow-up showed highly significant reductions in anxiety symptoms, anxious cognition, agoraphobic avoidance, general symptomatology, and depressive symptoms. Results did not differ significantly between the 3 outpatient clinics and are comparable with the average effect sizes reported by meta-analytic studies of controlled efficacy research, using selected patients and specifically trained therapists. Effectiveness was not dependent on duration of disorder, number of treatment sessions, and therapist experience. The study suggests that high-density exposure can be transported from research settings to the mental health field.

Adolescent↗
PubMed2001

No free lunch.

Explore the source record for details and available documents.

Internet↗
PubMed2001

A double-blind trial of perindopril and nitrendipine in incipient diabetic nephropathy.

UNLABELLED: We conducted a randomised, double-blind multicentre trial to compare the efficacy of the inhibitor of the angiotensin-converting enzyme (ACE) perindopril (P) with nitrendipine (N) in incipient diabetic nephropathy. METHODS: Forty-six patients with insulin-treated diabetes mellitus and mild-to-moderate hypertension and stable microalbuminuria were examined. P 4 or 8 mg once daily was compared to N 20 or 40 mg once daily; an optional open combination treatment with indapamide 2.5 mg once daily was given when needed. Main outcome measures were urinary albumin excretion rate, creatinine clearance and isotopic clearance measurements after 12 months. RESULTS: Baseline characteristics (blood pressure, HbA1, renal function) were highly comparable between groups. No serious adverse events occurred during the study period. Blood pressure was controlled (<140/90 mmHg) in all patients except for one in each group who dropped out. At the end of the study, albumin excretion rate was stabilized in both groups (P: 72% of baseline, N: 108%, NS). There were no significant differences found in radiometric clearance measurements. Creatinine clearance rose in patients treated with P by 10.0 ml/min on average, while it decreased by 9.8 m/min under N treatment (group effect: p<0.05). CONCLUSIONS: In this head-to-head comparison, P and N were effective in stabilising most parameters of renal function in incipient diabetic nephropathy.

Adolescent↗
PubMed2000

[Results of neurorehabilitation. An outcome study 20 months after stroke].

65 stroke survivors who were discharged home after completing an in-patient rehabilitation program were evaluated at home 20 months post-stroke by physiotherapists. 59 patients (91%) still lived in the community. Functional abilities remained stable with only 11% deteriorating and 25% improving in basal activities of daily living (BADL). 58% of patients needed assistance for at least one BADL and 46% showed signs of impaired cognition. Falls occurred in more than half of patients. Rehospitalisation was common (31%). Aside from living partners, care was provided by relatives in 58% and by home services in 46%. 25% of patients attended day care. Nearly half of patients still received rehabilitative therapy, especially if marked initial deficit was present. In conclusion, 20 months post stroke the majority of survivors who have completed rehabilitation successfully experience persistent limitations but remain in a stable functional status. This seems to be true for more severely disabled patients, too, if rehabilitative therapies, home services and day care are consequently provided.

Activities of Daily Living↗
PubMed2000

A new combined computational and NMR-spectroscopical strategy for the identification of additional conformational constraints of the bound ligand in an aprotic solvent.

This study documents the feasibility of switching to an aprotic medium in sugar receptor research. The solvent change offers additional insights into mechanistic details of receptor--carbohydrate ligand interactions. If a receptor retained binding capacity in an aprotic medium, solvent-exchangeable protons of the ligand would not undergo transfer and could act as additional sensors, thus improving the level of reliability in conformational analysis. To probe this possibility, we first focused on hevein, the smallest lectin found in nature. The NMR-spectroscopic measurements verified complexation, albeit with progressively reduced affinity by more than 1.5 orders of magnitude, in mixtures of up to 50% dimethyl sulfoxide (DMSO). Since hevein lacks the compact beta-strand arrangement of other sugar receptors, such a structural motif may confer enhanced resistance to solvent exchange. Two settings of solid-phase activity assays proved this assumption for three types of alpha- and/or beta-galactoside-binding proteins, that is, a human immunoglobulin G (IgG) subfraction, the mistletoe lectin, and a member of the galectin family of animal lectins. Computer-assisted calculations and NMR experiments also revealed no conspicuous impact of the solvent on the conformational properties of the tested ligands. To define all possible nuclear Overhauser effect (NOE) contacts in a certain conformation and to predict involvement of exchangeable protons, we established a new screening protocol applicable during a given molecular dynamics (MD) trajectory and calculated population densities of distinct contacts. Experimentally, transferred NOE (tr-NOE) experiments with IgG molecules and the disaccharide Gal'alpha1-3Galbeta1-R in DMSO as solvent disclosed that such an additional crosspeak, that is, Gal'OH2--GalOH4, was even detectable for the bound ligand under conditions in which spin diffusion effects are suppressed. Further measurements with the plant lectin and galectins confirmed line broadening of ligand signals and gave access to characteristic crosspeaks in the aprotic solvent and its mixtures with water. Our combined biochemical, computational, and NMR-spectroscopical strategy is expected to contribute notably to the precise elucidation of the geometry of ligands bound to compactly folded sugar receptors and of the role of water molecules in protein--ligand (carbohydrate) recognition, with relevance to areas beyond the glycosciences.

Antimicrobial Cationic Peptides↗
PubMed2000

NMR spectra of fluorinated carbohydrates.

Recent advances in structural and conformational analysis of fluorinated carbohydrates by NMR spectroscopy are reviewed. Characteristic 1H, 13C, and 19F NMR chemical shifts and coupling constants for selected examples are given and the spectral data of a series of fluorinated carbohydrates were collected in continuation of the review of Csuk and Glänzer [Adv. Carbohydr. Chem. Biochem., 46 (1988) 73-177].

Carbohydrates↗
PubMed2000

Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1.

The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats. Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C). Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.

3T3 Cells↗
PubMed2000

Investigating ion-surface collisions with a niobium superconducting tunnel junction detector in a time-of-flight mass spectrometer

The performance of an energy sensitive, niobium superconducting tunnel junction (STJ) detector is investigated by measuring the pulse height produced by impacting molecular and atomic ions at different kinetic energies. Ions are produced by laser desorption and matrix-assisted laser desorption in a time-of-flight mass spectrometer. Our results show that the STJ detector pulse height decreases for increasing molecular ion mass, passes through a minimum at around 2000 Da, and then increases with increasing mass of molecular ions above 2000 Da. The detector does not show a decline in sensitivity for high mass ions as is observed with microchannel plate ion detectors. These detector plus height measurements are discussed in terms of several physical mechanisms involved in an ion-surface collision.

Journal Article↗
PubMed2000

Using a superconducting tunnel junction detector to measure the secondary electron emission efficiency for a microchannel plate detector bombarded by large molecular ions

An energy-sensitive superconducting tunnel junction (STJ) detector was used to measure the secondary electron emission efficiency, epsilon(e), for a microchannel plate (MCP) detector bombarded by large (up to 66 kDa), slow moving (<40 km/s) molecular ions. The method used is new and provides a more direct procedure for measuring the efficiency of secondary electron emission from a surface. Both detectors were exposed simultaneously to nearly identical ion fluxes. By exposing only a small area of the MCP detector to ions, such that the area exposed was effectively the same as the size of the STJ detector, the number of ions detected with each detector were directly comparable. The STJ detector is 100% efficient for detecting ions in the energy regime investigated and therefore it can be used to measure the detection efficiency and secondary electron emission efficiency of the MCP. The results are consistent with measurements made by other groups and provide further characterization of the loss in sensitivity noted previously when MCP detectors have been used to detect high-mass ions. Individual molecular ions of mass 66 kDa with 30 keV kinetic energy were measured to have about a 5% probability of producing one or more electrons when impacting the MCP. When ion energy was reduced to 10 keV, the detection probability decreased to 1 %. The secondary electron yield was calculated from the secondary electron emission efficiency and found to scale linearly with the mass of the impinging molecular ion and to about the fourth power of ion velocity. Secondary electrons were observed for primary ion impacts >5 km/s, regardless of mass, and no evidence of a velocity (detection) threshold was observed. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

A comparison of the microstructure and properties of the IPS Empress 2 and the IPS Empress glass-ceramics.

The aim of this report is to analyze the microstructures of glass-ceramics of the IPS Empress 2 and IPS Empress systems by scanning electron microscopy. The main properties of the glass-ceramics were determined and compared to each other. The flexural strength of the pressed glass-ceramic (core material) was improved by a factor of more than three for IPS Empress 2 (lithium disilicate glass-ceramic) in comparison with IPS Empress (leucite glass-ceramic). For the fracture toughness, the K(IC) value was measured as 3.3 +/- 0.3 MPa. m(0.5) for IPS Empress 2 and 1.3 +/- 0.1 MPa. m(0.5) for IPS Empress. Abrasion behavior, chemical durability, and optical properties such as translucency of all glass-ceramics fulfill the dental standards. The authors concluded that IPS Empress 2 can be used to fabricate 3-unit bridges up to the second premolar.

Ceramics↗
PubMed2000

Do picture archiving and communication systems improve report turnaround times?

Radiology departments are beginning to embrace new technologies to decrease operating budgets and improve services. One of these technologies is the picture archiving and communication system (PACS). PACS, through immediate availability of images to the radiologist, promises to decrease turnaround times of reports to the clinician. The purpose of this study was to determine if this technology actually decreases the time for referring clinicians to receive reports generated by the radiologist. The time to provide a preliminary report by a resident and time to finalize this report by a board-certified radiologist was retrospectively obtained for 6,022 abdominal and pelvic computed tomography (CT) scans over two 1-year periods from March 1, 1997 to March 1, 1998 and from March 1, 1998 to March 1, 1999. During the first year, interpretation was conducted using hard-copy film and during the second using PACS. In both 1-year periods, MedSpeak voice recognition software (IBM, White Plains, NY) was employed for dictation. The average time for a preliminary report for a abdominal and pelvic CT, dictated by a resident or fellow, to be available in alphanumeric form on the hospital information system using hard-copy film was 3.73 days. The installation of a PACS system decreased this turnaround time to 0.56 days, representing an 85.0% improvement. The time to availability of final reports, ie, signed by board-certified staff radiologists, was 5.49 days in the hard-copy interpretation subset and 5.97 days in the PACS subset. The addition of PACS into an academic gastrointestinal radiology division improves availability of alphanumeric preliminary reports of abdominal and pelvic CTs on the hospital information system (HIS), dictated by a resident or fellow, by 85.0%. There was no impact with a PACS on the time to final sign reports by a staff board certified radiologist as signing patterns remained relatively constant over the two interpretation formats.

Data Display↗
PubMed2000

MAL, a proteolipid in glycosphingolipid enriched domains: functional implications in myelin and beyond.

The myelin and lymphocyte protein MAL (VIP17/MVP17) is a proteolipid of 17 kD with a hydrophobicity pattern that indicates a four transmembrane domain structure. The MAL cDNA has been cloned from human T-cells, rat oligodendrocytes and the Madin-Darby canine kidney (MDCK) cell line. In the nervous system both myelinating cells, oligodendrocytes and Schwann cells, express MAL protein. MAL expression parallels myelin formation, and MAL is predominantly localized in compact myelin. Prior to myelin formation MAL is also found in immature Schwann cells. Outside the nervous system MAL expression is found in T-cells and in distinct epithelial cells, e.g. in kidney, stomach and thyroid gland, where MAL is localised in the apical plasma membrane. Specific glycosphingolipids, e.g. galactosylceramide and sulfatide, are enriched in such apical kidney and stomach membranes as well as in myelin. MAL copurifies with these glycosphingolipids in detergent insoluble domains, indicating a close association and possible functional interactions of MAL with glycosphingolipids in these tissues. Moreover, recent reports point to additional functions of MAL-glycosphingolipid complexes in signalling, cell differentiation and apical sorting. The role of MAL in the formation, stabilisation and maintenance of glycosphingolipid-enriched membrane microdomains and its contribution to specific membrane properties in myelin and epithelial cells are discussed.

Amino Acid Sequence↗
PubMed2000

Needle-like apatite-leucite glass-ceramic as a base material for the veneering of metal restorations in dentistry.

A needle-like apatite-leucite glass-ceramic was prepared in the SiO2-Al2O3-Na2O-K2O-P2O5-F system. Nucleation and crystallization processes were studied in bulk and powdered samples. The crystallization of leucite follows the mechanism of surface crystallization. After the precipitation of NaCaPO4 crystals and another unknown crystal phase, the formation of needle-like apatite is based on a volume nucleation and crystallization process. The mechanism of the formation of needle-like apatite differs to those of apatite precipitation in glass-ceramics. The morphology of needle-like apatite is comparable to that of apatite in natural teeth. The properties of the glass-ceramic, especially the good chemical durability, the optical properties, as well as mechanical and thermal properties allow glass-ceramic to be used as a main component in a bio-material for the veneering of metal restorations in dentistry.

Journal Article↗