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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 37 records · Page 2Linked to original sources
PubMed2002

Characterization of thin polymer and biopolymer layers by ellipsometry and evanescent field technology.

The characterization of sensitive layers is the prerequisite for the optimization of chemical and biochemical sensors. The application of SE (Spectral Ellipsometry) and SPR (Surface Plasmon Resonance) as methods of characterization of such sensitive layers is discussed. In combination with infrared spectroscopy, the properties of polymer networks, micro-porous polymers, liquid crystals, and biomimetic polymers can be examined regarding their applicability for optical sensing. Apart from the basic principles regarding the characterization approaches, applications in the area of environmental sensing, optimization of hydrogel layers for antigen/antibody interaction, and discrimination of analytes in homologous series of alcohols are discussed. The effects of analytes on the phase transition in combination with disordering of liquid crystals are given.

Biopolymers↗
PubMed2002

Homeopath & patient--a dyad of harmony?

Within the last 20 yr, heterodox medicine has become increasingly popular in western societies. Critics and advocates argue that the physician-patient relationship is a key factor to this success. This study which is based on 20 semi-structured interviews with homeopathic physicians in Berlin questions the notion of a purely consensual interaction. While we can find a certain degree of partnership between homeopathic physicians and their patients, there is a significant amount of negotiation and disagreement as well: The arenas are the revelation of the prescribed homeopathic remedy, patients' expectations, the physicians' fees and differing views on the appropriate duration of consultation. Consequently, a rather complex picture of the physician-patient interaction emerges which challenges the notion of a purely harmony- and consumer-oriented consultation in heterodox medicine. It does not seem possible straightforwardly to apply any of the existing theoretical models to the physician-patient relationship.

Appointments and Schedules↗
PubMed2002

Monitoring of tumour glucose metabolism by PET in a phase I study evaluating hormonal therapy in advanced pancreatic cancer.

BACKGROUND: Positron emission tomography (PET) determines therapy-induced changes in tumour glucose utilization. Experimental data indicate that cholecystokinin (CCK) stimulates pancreatic cancer growth. In this study in patients with advanced pancreatic cancer, we evaluated the use of fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging (MRI) in monitoring hormonal therapy using a highly selective, non-peptide CCK receptor antagonist (SR 27897B). METHODS: Nineteen patients were enrolled on a 28-day course of SR 27897B. Initially, 4 patients received 20 mg of SR 27897B; 9 patients received 40 mg; and 6 patients 80 mg. Imaging studies, including FDG-PET and MRI, were performed at baseline and on days 14 and 28. RESULTS: No significant changes in FDG uptake by the primary tumours were observed. Rate of progression of disease was 11 (61%) of 18 evaluable patients by MRI. Median survival of all patients enrolled was 2.7 months. SR 27897B was fairly well tolerated at all doses tested. The most common side effects were gastrointestinal disorders such as diarrhoea, flatulence and nausea. CONCLUSION: SR 27897B, when used alone at the limited doses employed, led neither to an impairment of tumour glucose metabolism nor to a reduction of tumour size in advanced pancreatic cancer.

Adenocarcinoma↗
PubMed2002

[Atrial flutter with 1/1 nodo-ventricular conduction with amiodarone. From physiopathology to diagnosis].

Atrial flutter with 1/1 nodo-ventricular conduction is a classical complication of Vaughan-Williams's Class I antiarrhythmic drugs. The increase of the flutter cycle and weak action of the antiarrhythmic on the atrioventricular node leads to 1/1 conduction of atrial depolarisation to the ventricles. In view of their marked action on the atrioventricular node, this type of pro-arrhythmic effect is very unexpected with Class III antiarrhythmics. The authors report 7 cases of 1/1 atrial flutter with oral amiodarone observed between 1994 and 2001. The patients were 6 men and 1 woman with an average age of 58 +/- 14 years. Four of them had underlying cardiac disease; none were hyperthyroid. The initial arrhythmia was 2/1 atrial flutter (n = 4), 1/1 atrial flutter (n = 2) and atrial fibrillation (n = 1). Treatment was preventive with doses of 400 mg/day associated with carvedilol in one patient and 200 mg/day in another. The other five patients all received loading doses of 9200 +/- 2400 mg over 10 +/- 4 days. The symptoms were palpitations (n = 2) associated in one patient with hypotension, one syncope, one near syncope and one cardiogenic shock. The ventricular cycle of the 1/1 flutter was 287 +/- 33 ms. The QRS duration was 136 +/- 35 ms with ventricular tachycardia-like appearances in 3 cases. An adrenergic trigger factor was noted in 5 patients. One patient required emergency cardioversion. The authors discuss the physiopathology of 1/1 flutter and theoretical diagnostic methods are proposed. In conclusion, amiodarone does not always prevent the occurrence of 1/1 nodo-ventricular conduction in atrial flutter.

Administration, Oral↗
PubMed2001

Repetitive ozone exposure of young adults: evidence of persistent small airway dysfunction.

Earlier, we found that acute ozone (O3) exposure caused, along with inflammation, greater, more protracted changes in small airway function (isovolumetric V max at intermediate to low lung volumes) than in FVC or FEV1. To test if this distinction prevailed with repetitive O3 exposure, we exposed eight healthy adults on four consecutive days alternatively to filtered air (FA) and O3 (0.25 ppm x 2 h). Isovolumetric FEF25-75, Vmax50, and Vmax75, were grouped into a single value representing small airway function (SAW(grp)); respiratory frequency (f) and tidal volume (VT) were monitored during exercise. On Day 5, peripheral airway resistance (Rp) was measured followed by lavage. All daily spirometric and ventilatory changes declined in magnitude (adapted) after one or more days of O3 exposure. In addition, SAW(grp), f, and VT showed persistent changes beginning with Day 2, denoted either by depression of the preexposure baseline (SAW(grp)) or exaggerated tachypnea during exercise. O3-induced neutrophilia (p = 0.04) was present in lavage fluid. The possible relationship between these persistent changes in small airway function, measured in days, and the likelihood of cumulative injury in the same region if exposure is long term, is unknown.

Adult↗
PubMed2001

Identification of novel bifunctional calmodulin-binding and microtubule-stabilizing motifs in STOP proteins.

Although microtubules are intrinsically labile tubulin assemblies, many cell types contain stable polymers, resisting depolymerizing conditions such as exposure to the cold or the drug nocodazole. This microtubule stabilization is largely due to polymer association with STOP proteins. There are several STOP variants, some with capacity to induce microtubule resistance to both the cold and nocodazole, others with microtubule cold stabilizing activity only. These microtubule-stabilizing effects of STOP proteins are inhibited by calmodulin and we now demonstrate that they are determined by two distinct kinds of repeated modular sequences (Mn and Mc), both containing a calmodulin-binding peptide, but displaying different microtubule stabilizing activities. Mn modules induce microtubule resistance to both the cold and nocodazole when expressed in cells. Mc modules, which correspond to the STOP central repeats, have microtubule cold stabilizing activity only. Mouse neuronal STOPs, which induce both cold and drug resistance in cellular microtubules, contain three Mn modules and four Mc modules. Compared with neuronal STOPs, the non-neuronal F-STOP lacks multiple Mn modules and this corresponds with an inability to induce nocodazole resistance. STOP modules represent novel bifunctional calmodulin-binding and microtubule-stabilizing sequences that may be essential for the generation of the different patterns of microtubule stabilization observed in cells.

Amino Acid Motifs↗
PubMed2001

The N-terminal domain of Homer/Vesl is a new class II EVH1 domain.

Cellular activities controlled by signal transduction processes such as cell motility and cell growth depend on the tightly regulated assembly of multiprotein complexes. Adapter proteins that specifically interact with their target proteins are key components required for the formation of these assemblies. Ena/VASP-homology 1 (EVH1) domains are small constituents of large modular proteins involved in microfilament assembly that specifically recognize proline-rich regions. EVH1 domain-containing proteins are present in neuronal cells, like the Homer/Vesl protein family that is involved in memory-generating processes. Here, we describe the crystal structure of the murine EVH1 domain of Vesl 2 at 2.2 A resolution. The small globular protein consists of a seven-stranded antiparallel beta-barrel with a C-terminal alpha-helix packing alongside the barrel. A shallow groove running parallel with beta-strand VI forms an extended peptide-binding site. Using peptide library screenings, we present data that demonstrate the high affinity of the Vesl 2 EVH1 domain towards peptide sequences containing a proline-rich core sequence (PPSPF) that requires additional charged amino acid residues on either side for specific binding. Our functional data, substantiated by structural data, demonstrate that the ligand-binding of the Vesl EVH1 domain differs from the interaction characteristics of the previously examined EVH1 domains of the Evl/Mena proteins. Analogous to the Src homology 3 (SH3) domains that bind their cognate ligands in two distinct directions, we therefore propose the existence of two distinct classes of EVH1 domains.

Amino Acid Sequence↗
PubMed2001

Prognostic value of radionuclide angiography in patients with right ventricular arrhythmias.

BACKGROUND: The prognosis of patients with right ventricular (RV) arrhythmias remains uncertain. This study prospectively evaluated the prognostic value of RV and left ventricular (LV) involvement assessed by radionuclide angiography (RNA) as predictors for sudden death. METHODS AND RESULTS: Patients (n=188) with severe arrhythmias originating from the RV were followed up for a mean of 45+/-34 months. Data on clinical presentation, resting and stress ECG, signal-averaged ECG, 24-hour Holter monitoring, and programmed stimulation were collected along with RNA. Patients were classified as group I (n=82) with normal RNA or group II (n=106) with an abnormal RV suggestive of arrhythmogenic RV cardiomyopathy, classified as diffuse or localized disease, with or without associated LV abnormalities. During follow-up, 14 patients died suddenly, all in group II. None of the clinical and electrical data were predictive of death. An abnormal RNA study was a highly predictive factor for death (P<0.005), as well as the presence of LV abnormalities (P<0.01). CONCLUSIONS: The present study confirms that arrhythmogenic RV cardiomyopathy is a severe disease with a high risk for cardiac death. Evidence of RV abnormalities in patients presenting with RV arrhythmias is highly predictive for sudden death, as is its association with LV involvement.

Adolescent↗
PubMed2001

Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability.

Vascular endothelial cadherin (VE-cadherin) is an endothelial cell-specific cadherin that plays an important role in the control of vascular organization. Blocking VE-cadherin antibodies strongly inhibit angiogenesis, and inactivation of VE-cadherin gene causes embryonic lethality due to a lack of correct organization and remodeling of the vasculature. Hence, inhibitors of VE-cadherin adhesive properties may constitute a tool to prevent tumor neovascularization. In this paper, we tested different monoclonal antibodies (mAbs) directed to human VE-cadherin ectodomain for their functional activity. Three mAbs (Cad 5, BV6, BV9) were able to increase paracellular permeability, inhibit VE-cadherin reorganization, and block angiogenesis in vitro. These mAbs could also induce endothelial cell apoptosis in vitro. Two additional mAbs, TEA 1.31 and Hec 1.2, had an intermediate or undetectable activity, respectively, in these assays. Epitope mapping studies show that BV6, BV9, TEA 1.31, and Hec 1.2 bound to a recombinant fragment spanning the extracellular juxtamembrane domains EC3 through EC4. In contrast, Cad 5 bound to the aminoterminal domain EC1. By peptide scanning analysis and competition experiments, we defined the sequences TIDLRY located on EC3 and KVFRVDAETGDVFAI on EC1 as the binding domain of BV6 and Cad 5, respectively. Overall, these results support the concept that VE-cadherin plays a relevant role on human endothelial cell properties. Antibodies directed to the extracellular domains EC1 but also EC3-EC4 affect VE-cadherin adhesion and clustering and alter endothelial cell permeability, apoptosis, and vascular structure formation.

Antibodies, Monoclonal↗
PubMed2001

A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model.

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P <.001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.

Adolescent↗
PubMed2001

The effect of HIV-1 regulatory proteins on cellular genes: derepression of the IL-2 promoter by Tat.

In HIV-infected individuals dysregulation of the immune system is characterized by severe disorders of the cytokine network. Increase secretion of IL-2, the major T cell growth and differentiation cytokine, may play a decisive role in sensitization of T cells for activation induced apoptosis and indirect death of activated T cells through augmented virus replication. We investigated the cause of enhanced IL-2 secretion and found that the HIV Tat induces this effect. We demonstrate that increased IL-2 secretion is due to Tat-enhanced IL-2 promoter activation. Tat derepresses and activates the distal AP-1 site (position -185 to -177) in the IL-2 promoter. In nonstimulated T cells a repressor complex containing NF-IL6, JunB, c-Fos and Fra-1 is formed on the AP-1(IL-2/d) site and represses IL-2 promoter activity. After T cell activation, a heterodimeric activator containing p65 and c-Jun binds to the AP-1(IL-2/d) site. HIV Tat enhances activation of NF-kappaB and consequently, activates the AP-1(IL-2/d) site. Our data provide evidence for a novel mechanism by which HIV Tat dysregulates IL-2 production and therefore may contribute to the HIV-1 infection in a way yet to be clarified.

Binding Sites↗
PubMed2001

Subcellular distribution of 14-3-3 proteins in the unicellular green alga Chlamydomonas reinhardtii.

A polyclonal antibody was raised against a recombinant Chlamydomonas 14-3-3-beta-galactosidase (beta-Gal) fusion protein and characterized for its epitope specificity towards the corresponding Chlamydomonas 14-3-3 protein by scan-peptide analysis. This antibody recognized four Chlamydomonas polypeptides with apparent molecular masses 32, 30, 27, and 24 kDa, which also reacted with the antiserum depleted of anti-(Escherichia coli beta-Gal) IgG, but not with the corresponding preimmune serum or the antiserum preincubated with purified 14-3-3 proteins. Western-blot analyses performed with the antibody depleted of anti-(beta-Gal) IgG revealed that more or less pronounced levels of 14-3-3 proteins were present in all subcellular fractions of Chlamydomonas reinhardtii except the nuclei. The highest levels of 14-3-3 protein were observed in the cytosol and microsomal fraction. The 30-kDa isoform was predominant in the cytosol, whereas the 27-kDa isoform was prevalent in the microsomes. When microsomal membranes were separated by sucrose-density-gradient centrifugation, Western-blot analysis revealed distinct patterns of 14-3-3 isoforms in the endoplasmic reticulum, dictyosome, and plasma membrane fractions identified by marker enzyme activities. These findings indicate that the four 14-3-3 proteins of C. reinhardtii differentially interact with endoplasmic reticulum, dictyosomes, and plasma membrane.

14-3-3 Proteins↗
PubMed2001

Defining the mycoplasma 'cytoskeleton': the protein composition of the Triton X-100 insoluble fraction of the bacterium Mycoplasma pneumoniae determined by 2-D gel electrophoresis and mass spectrometry.

After treating Mycoplasma pneumoniae cells with the nonionic detergent Triton X-100, an undefined, structured protein complex remains that is called the 'Triton X-100 insoluble fraction' or 'Triton shell'. By analogy with eukaryotic cells and supported by ultrastructural analyses it is supposed that this fraction contains the components of a bacterial cytoskeleton-like structure. In this study, the composition of the Triton X-100 insoluble fraction was defined by electron microscopic screening for possible structural elements, and by two-dimensional (2-D) gel electrophoresis and MS to identify the proteins present. Silver staining of 2-D gels revealed about 100 protein spots. By staining with colloidal Coomassie blue, about 50 protein spots were visualized, of which 41 were identified by determining the mass and partial sequence of tryptic peptides of individual proteins. The identified proteins belonged to several functional categories, mainly energy metabolism, translation and heat-shock response. In addition, lipoproteins were found and most of the proteins involved in cytadherence that were previously shown to be components of the Triton X-100 insoluble fraction. There were also 11 functionally unassigned proteins. Based on sequence-derived predictions, some of these might be potential candidates for structural components. Quantitatively, the most prevalent proteins were the heat-shock protein DnaK, elongation factor Tu and subunits alpha and beta of the pyruvate dehydrogenase complex (PdhA, PdhB), but definite conclusions regarding the composition of the observed structures can only be drawn after specific proteins are assigned to them, for example by immunocytochemistry.

Bacterial Proteins↗
PubMed2001

Assessing homeostasis through circadian patterns.

An organism is thought to be in a dynamic state of homeostasis when each physiological and behavioral system reaches a delicate balance within the framework of other regulatory processes. Many biological systems target specific set-point variables and generate circadian patterns. In this article, we focus on specific measurements representative of two systems, namely deep-body temperature and activity counts. We examine data collected every 30 minutes in mice, assume there are underlying circadian patterns, and extend the approach presented in Brumback and Rice (1998, Journal of the American Statistical Association 93, 961-976) in order to obtain estimates in the presence of correlated data. We then assess homeostasis using these estimates and their statistical properties.

Animals↗
PubMed2001

The misuse of biology in demographic research on racial/ethnic differences: a reply to van den Oord and Rowe.

In an article in the August 2000 issue of Demography titled "Racial Differences in Birth Health Risk: A Quantitative Genetic Approach," van den Oord and Rowe attempted to study the genetic and environmental factors contributing to the black/white gap in infant birth weight. Their findings indicate that this difference may be explained by shared environmental influences rather than by fetal genes. Yet the authors insisted in their conclusions that a strong genetic component still must play a role in determining the racial gap in birth weight, if only through maternal effects. The incompatibility between the authors' findings and their conclusions is due largely to a weakness in their conceptualization of the relationship between race and biology. Their insistence that racial groups represent discrete genetic entities, coupled with a failure to account for interactions between biological and environmental processes, illustrates the methodological and ethical problems that threaten future interdisciplinary research on racial/ethnic disparities in health.

Biological Phenomena↗