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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 109 records · Page 6Linked to original sources
PubMed1998

Three-dimensional computed tomography of the reconstructed lower urinary tract: technique and findings.

The aim of this pilot study in 54 patients was to improve the visualization of the anatomy and postoperative changes in the pelvic topography after bilateral ureteroileal urethrostomy, using surface rendering of electron beam CT (EBCT) data for the 3D display. Fifty-four patients (39 men and 15 women) were scanned with an EBCT unit between 3 and 110 months after performing orthotopic ureteroileal urethrostomy ("Hemi-Kock") or ureteroileal rectosigmoidostomy. Various parameters and spatial viewing points were used in the 3D reconstruction, which was performed interactively on external workstations with commercially available software. The anti-reflux nipple was visualized as a distinct structure in all patients. In 8 patients with an interval of more than 12 months between surgery and CT, the pouch had developed an ovoid shape almost indistinguishable from the original bladder. The segmented data sets were partly animated to display the anatomy as virtual endoscopy. Three-dimensional depiction and virtual endoscopy of the neobladder using EBCT are a new way of imaging the postoperative anatomy. Its clinical efficacy in the diagnosis of inconclusive postoperative morbidity, especially voiding problems, and planning of necessary therapy have to be the subject of further evaluation.

Adult↗
PubMed1998

Affective distress in fibromyalgia syndrome is associated with pain severity.

OBJECTIVE: Comparison of low back pain (LBP) patients with and without fibromyalgia syndrome (FMS) with regard to affective distress. METHODS: Patients with LBP who had been admitted to various clinics in Germany were examined upon admission. Comparisons were done by dividing the patients into groups with and without signs of FMS. Additionally, both groups were compared after being matched according to sex, age, and pain severity. RESULTS: 15 out of 135 LBP patients met the American College of Rheumatology criteria for fibromyalgia. Patients with FMS showed remarkably higher levels of pain severity and affective distress. After controlling for different levels of pain severity, these pronounced differences disappeared. CONCLUSION: Affective distress is not a unique feature of FMS, but seem to be caused entirely by higher levels of pain severity.

Adult↗
PubMed1998

Different expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein in human keratinocytes and fibroblasts.

We compared, using a combination of different immunological methods and by competitive PCR, the expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein (alpha2-M-R/LRP) in human keratinocytes and fibroblasts. This receptor has previously been found in skin only in dermal cells associated with fibroblasts and dendritic cells. For immunodetection we used mouse monoclonal antibodies against the two subunits of the receptor and against the receptor-associated protein (RAP), known as the regulatory protein of the receptor activity. The alpha2-M-R/LRP was found to be predominantly located intracellularly in keratinocytes whereas a distinct labelling of the outer membrane surface was found in fibroblasts. RAP is abundant in fibroblasts but is less expressed in keratinocytes. In frozen skin sections receptor immunoreactivity was detected in the epidermis with increased reactivity of basal keratinocytes, as well as in the dermis in association with dermal fibroblasts. By immunoprecipitation of biotinylated cell extracts, polypeptides were identified corresponding to the alpha-subunit and beta-subunit of the receptor as well as to the coprecipitating RAP. Competitive PCR revealed the presence of 67.9 and 2049.7 ag of alpha2-M-R/LRP mRNA per cell in keratinocytes and fibroblasts, respectively. The results demonstrate that both cell types express alpha-M-R/LRP mRNA and contain receptor protein as well as RAP but in different quantities and subcellular localizations.

Animals↗
PubMed1998

Structural complexity and the time course of grammatical development.

One traditional view of the time course of language acquisition holds that a child's difficulties in learning her language are due to general processing, memory or conceptual limitations. As the child's cognitive capacities expand, so do her abilities to use her already-acquired grammar or to recognize additional properties of her soon-to-be native language. Recent work in the study of child language, however, has discovered the existence of a number of characteristic stages, transitions between which are best described in the terms of linguistic theory proper. These stages are surprising under a view of language acquisition according to which developmental delay derives from general cognitive limitations, which cannot characterize difficulties explicable only in language-specific terms. At the same time, current linguistic theories so severely restrict the variation among possible human grammars that there remains little reason why there should be any learning problem at all or characteristic developmental stages. In this paper, I propose that these two views can be reconciled. I show that children's difficulties with a wide range of syntactic constructions, which are indeed best defined in linguistic terms, should nonetheless be derived from limitations on the child's ability to deal with processing load and formal representational complexity. I suggest however that this can be done only in the context of a particular view of syntactic representation, one which is articulated in the terms of the formal system of tree adjoining grammar (TAG). I demonstrate how precisely those difficulties that children experience in the acquisition of relative clauses, adjectival modification, control constructions, raising, wh-questions and the obligatoriness of finite inflection can be traced to the complexity associated with one of the TAG combinatory operations, adjoining. This proposal relates this apparently disparate set of constructions in a novel way and provides us with a new type of explanation for the time course of syntactic development in terms of the complexity of formal grammatical devices.

Child↗
PubMed1998

[Implanted automatic defibrillator after ventricular fibrillation treated with semi-automatic defibrillation].

We report two cases of out-of-hospital ventricular fibrillation treated without delay, with basic life support practiced by the witness, followed by a successful defibrillation by paramedics with a semi-automatic defibrillator. In the subsequent month, a cardioverter-defibrillator was implanted. In one patient, a ventricular tachycardia occurring 10 months later and a ventricular fibrillation 9 months later in the other respectively, were successfully reversed by the implanted defibrillator. These two cases illustrate the value of the "survival chain" concept (undelayed alert, basic life support by witness, early defibrillation by paramedics with a semi-automatic defibrillator, advanced life support by a physician) as well as the benefit of the implanted cardioverter-defibrillator.

Adult↗
PubMed1998

3-Dimensional computerized tomography and virtual reality endoscopy of the reconstructed lower urinary tract.

PURPOSE: We describe postoperative surgical anatomy after orthotopic reconstruction of the lower urinary tract using 3-dimensional (D) computerized tomography (CT) and virtual reality endoscopy. MATERIALS AND METHODS: Electronic beam CT was performed in 39 men and 15 women a mean of 60 years old with an orthotopic ileal neobladder (50) or ureteroileal rectosigmoidostomy (4), followed by 3-D reconstruction of the pelvic anatomical structures using specialized computer hardware and software. The mean interval between surgery and CT was 15 months (range 3 to 110) and the mean interval between 2 subsequent 3-D CT studies in 22 patients was 6 months (range 3 to 9). RESULTS: CT time with the patient on the table was 45 minutes and computerized 3-D reconstruction time with the patient off the table was 4 to 5 hours. The pouch had a smooth ovoid shape in 66 and 82% of the patients on the first and second 3-D CT studies, respectively. Mean length of the antireflux nipple was 4 cm. (range 2.5 to 8) and mean length of the afferent limb was 6 cm. (range 3 to 15). There were no radiologically significant sex specific differences in the shape or dimensions of the urinary reservoirs, except for a tendency toward more acute angles between the pouch and remnant urethra. No pathological findings were visible on 3-D CT that were not also evident on conventional CT. CONCLUSIONS: Three-D CT may be clinically useful for surgical planning of a lower abdominal reoperation or unexplained findings and symptoms in patients with bladder substitutions. Cost and time expenditures for processing preclude its routine use in all cases. Virtual reality endoscopy may be a valuable tool for teaching and scientific purposes.

Adult↗
PubMed1998

Traveling through the decades: a special relationship between a pediatric nephrology nurse and a young adult.

The young adult that M.K. has become is in part of a result of the supportive relationship that I established with M.K. and her family over a decade ago. Viewing M.K. as a part of a family unit and not just as an isolated patient enabled the entire nephrology team to assist the family in dealing with the monumental medical problems that they have confronted. I am proud of the young woman that M.K. has become, and I am gratified by the relationship that we have shared for the past 16 years. It is this type of relationship that reminds me of why I decided to become a nurse many years ago.

Adolescent↗
PubMed1997

The N-terminal structure of HIV-1 Tat is required for suppression of CD26-dependent T cell growth.

Evidence exists that the human immunodeficiency virus-1 (HIV-1) transactivator Tat occurs extracellularly and is involved in the immunosuppression of non-HIV-1-infected T cells of acquired immunodeficiency syndrome (AIDS) patients. The mechanism of this immunosuppressive activity of Tat has been controversially discussed. Interestingly, Tat binds to the T cell activation marker CD26, which has been shown to play a key role in the regulation of growth of lymphocytes and to inhibit its dipeptidyl peptidase IV (DP IV) activity. Here we show that the N-terminal nonapeptide MDPVDPNIE of Tat is a competitive inhibitor of DP IV and suppresses DNA synthesis of tetanus toxoid-stimulated peripheral blood mononuclear cells. Amino acid exchanges at positions 5 and 6 strongly weaken these effects. 1H nuclear magnetic resonance and molecular dynamics simulations of Tat(1-9), I5-Tat(1-9), and L6-Tat(1-9) suggest a similar backbone conformation for Tat(1-9) and L6-Tat(1-9). The solution conformation of I5-Tat(1-9) considerably differs from the other two. However, Tat(1-9) fits into our previously proposed active site model of DP IV in contrast to I5-Tat(1-9) and L6-Tat(1-9). Conformational alterations with regard to the parent peptide and spatial hindrances between these both compounds and DP IV can explain the loss of inhibitory activity. Our data suggest that the N-terminal residues of HIV-1 Tat do interact directly with the active site of DP IV and that DP IV does mediate Tat's immunosuppressive effects.

Amino Acid Substitution↗
PubMed1997

Domains of neuronal microtubule-associated proteins and flexural rigidity of microtubules.

Microtubules are flexible polymers whose mechanical properties are an important factor in the determination of cell architecture and function. It has been proposed that the two most prominent neuronal microtubule-associated proteins (MAPs), tau and MAP2, whose microtubule binding regions are largely homologous, make an important contribution to the formation and maintenance of neuronal processes, putatively by increasing the rigidity of microtubules. Using optical tweezers to manipulate single microtubules, we have measured their flexural rigidity in the presence of various constructs of tau and MAP2c. The results show a three- or fourfold increase of microtubule rigidity in the presence of wild-type tau or MAP2c, respectively. Unexpectedly, even low concentrations of MAPs promote a substantial increase in microtubule rigidity. Thus at approximately 20% saturation with full-length tau, a microtubule exhibits >80% of the rigidity observed at near saturating concentrations. Several different constructs of tau or MAP2 were used to determine the relative contribution of certain subdomains in the microtubule-binding region. All constructs tested increase microtubule rigidity, albeit to different extents. Thus, the repeat domains alone increase microtubule rigidity only marginally, whereas the domains flanking the repeats make a significant contribution. Overall, there is an excellent correlation between the strength of binding of a MAP construct to microtubules (as represented by its dissociation constant Kd) and the increase in microtubule rigidity. These findings demonstrate that neuronal MAPs as well as constructs derived from them increase microtubule rigidity, and that the changes in rigidity observed with different constructs correlate well with other biochemical and physiological parameters.

Adsorption↗
PubMed1997

A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family.

The ActA protein of the intracellular pathogen Listeria monocytogenes induces a dramatic reorganization of the actin-based cytoskeleton. Two profilin binding proteins, VASP and Mena, are the only cellular proteins known so far to bind directly to ActA. This interaction is mediated by a conserved module, the EVH1 domain. We identify E/DFPPPPXD/E, a motif repeated 4-fold within the primary sequence of ActA, as the core of the consensus ligand for EVH1 domains. This motif is also present and functional in at least two cellular proteins, zyxin and vinculin, which are in this respect major eukaryotic analogs of ActA. The functional importance of the novel protein-protein interaction was examined in the Listeria system. Removal of EVH1 binding sites on ActA reduces bacterial motility and strongly attenuates Listeria virulence. Taken together we demonstrate that ActA-EVH1 binding is a paradigm for a novel class of eukaryotic protein-protein interactions involving a proline-rich ligand that is clearly different from those described for SH3 and WW/WWP domains. This class of interactions appears to be of general importance for processes dependent on rapid actin remodeling.

Amino Acid Sequence↗
PubMed1997

Prediction of head-up tilt test result by analysis of early heart rate variations.

BACKGROUND: Head-up tilt testing is a useful test for investigating vasovagal syncope. The determination of early, accurate, predictive criteria for a negative result would permit a reduction in the duration of the tilt test. METHODS AND RESULTS: Patients with no drug use and no illnesses other than recurrent unexplained syncope were recruited. In an initial study (110 consecutive patients), we aimed to determine a predictive criterion based on heart rate variations during the first minutes of upright tilting that could distinguish between patients with positive and negative tilt tests (patients with an early continual decrease in heart rate or blood pressure were excluded). Then we tested the predictive value of the established criterion in a second independent sample of patients with unexplained syncope (109 consecutive patients). An early sustained increase in heart rate < or = 18 bpm during the first 6 minutes of upright tilting at a 60 degree angle allowed us to predict negative tilt tests with 100% specificity, 100% positive predictive value, and 88.6% sensitivity. This criterion was validated in the second, prospective arm of the study (96.4% specificity, 98.4% positive predictive value, and 87.3% sensitivity), even with subsequent use of isoproterenol in low doses. CONCLUSIONS: In patients with no drug use and no illnesses other than recurrent unexplained syncope, a simple clinical criterion identifies patients who will not develop syncope during a prolonged upright tilt.

Adult↗
PubMed1997

HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation.

The proteasomal system consists of a proteolytic core, the 20 S proteasome, which associates in an ATP-dependent reaction with the 19 S regulatory complex to form the functional 26 S proteasome. In the absence of ATP, the 20 S proteasome forms a complex with the gamma-interferon-inducible 11 S regulator. Both the 20 S proteasome and the 11 S regulator have been implied in the generation of antigenic peptides. The human immunodeficiency virus (HIV)-1 Tat protein causes a number of different effects during acquired immunodeficiency syndrome (AIDS). Here we show that HIV-1 Tat protein strongly inhibits the peptidase activity of the 20 S proteasome and that it interferes with formation of the 20 S proteasome-11 S regulator complex. In addition, it slightly increases the activity of purified 26 S proteasome. These results may explain the mechanism by which HIV-1-infected cells escape cytotoxic T lymphocyte response and at least in part immunodeficiency in AIDS patients.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1997

NMR structure of inactivation gates from mammalian voltage-dependent potassium channels.

The electrical signalling properties of neurons originate largely from the gating properties of their ion channels. N-type inactivation of voltage-gated potassium (Kv) channels is the best-understood gating transition in ion channels, and occurs by a 'ball-and-chain' type mechanism. In this mechanism an N-terminal domain (inactivation gate), which is tethered to the cytoplasmic side of the channel protein by a protease-cleavable chain, binds to its receptor at the inner vestibule of the channel, thereby physically blocking the pore. Even when synthesized as a peptide, ball domains restore inactivation in Kv channels whose inactivation domains have been deleted. Using high-resolution nuclear magnetic resonance (NMR) spectroscopy, we analysed the three-dimensional structure of the ball peptides from two rapidly inactivating mammalian K. channels (Raw3 (Kv3.4) and RCK4 (Kv1.4)). The inactivation peptide of Raw3 (Raw3-IP) has a compact structure that exposes two phosphorylation sites and allows the formation of an intramolecular disulphide bridge between two spatially close cysteine residues. Raw3-IP exhibits a characteristic surface charge pattern with a positively charged, a hydrophobic, and a negatively charged region. The RCK4 inactivation peptide (RCK4-IP) shows a similar spatial distribution of charged and uncharged regions, but is more flexible and less ordered in its amino-terminal part.

Amino Acid Sequence↗
PubMed1997

Three T-cell epitopes within the C-terminal 265 amino acids of the matrix protein pp65 of human cytomegalovirus recognized by human lymphocytes.

Although a T-cell response in human cytomegalovirus (HCMV)-immune individuals exists against the most abundantly expressed protein pp65 of the virus matrix, less is known about the determinants that evoke this response. The aim of the study was to identify regions within HCMV pp65 (ppUL83) that contain sequences for the cellular immune response by the use of three recombinant overlapping beta-galactosidase pp65 fusion proteins (C74, C35, and C47), covering the C-terminal 265 amino acids of the entire pp65 sequence. Two T-cell epitope determinants were recognized by human lymphocytes of healthy, HCMV-seropositive, human leukocyte antigen (HLA)-typed individuals. One T-cell determinant (amino acids [aa] 303-388) was localized in the mid-region of the entire pp65 sequence and a second T-cell determinant (aa 477-561) within the C-terminal region. By fine mapping with synthetic hexadecamer peptides three T-cell epitopes were identified within these two regions: P10-I (aa 361-376) in the mid-region, P3-II (aa 485-499), and P6-II (aa 509-524) in the C-terminal region. Inhibition studies with monoclonal antibodies to HLA class I or class II revealed a class II restricted response to peptides P10-I or P6-II, respectively. P10-I responders shared the HLA-DR11 allele and P6-II responders the -DR3 allele. Therefore, these T-cell epitopes of HCMV pp65 might be presented in association with particular HLA class II alleles.

Alleles↗