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Biomedical subjects

D Vogel

Publications and source records attributed to D Vogel.

At least 19 recordsLinked to original sources
PubMed2003

Hypophonia in Parkinson's disease: neural correlates of voice treatment revealed by PET.

OBJECTIVE: To investigate the neural correlates of hypophonia in individuals with idiopathic PD (IPD) before and after voice treatment with the Lee Silverman Voice Treatment method (VT) using (15)O-H(2)O PET. METHODS: Regional cerebral blood flow (rCBF) changes associated with overt speech-motor tasks relative to the resting state were measured in the IPD subjects before and after VT, and in a group of healthy control volunteers. RESULTS: Behavioral measures of voice loudness significantly improved following treatment. Before VT, patients had strong speech-related activations in motor and premotor cortex (M1-mouth, supplementary motor cortex [SMA], and inferior lateral premotor cortex [ILPm]), which were significantly reduced post-VT. Similar to the post-treatment session, premotor activations were absent (SMA) or below statistical threshold (M1-mouth) in the healthy control group. In addition, following VT treatment, significant right-sided activations were present in anterior insular cortex, caudate head, putamen, and dorsolateral prefrontal cortex (DLPFC). Finally, the VT-induced neural changes were not present with transient experimenter-cued increases of loudness in VT-untreated patients. CONCLUSIONS: Effective improvement of IPD hypophonia following voice treatment with VT was accompanied by a reduction of cortical motor-premotor activations, resembling the functional pattern observed in healthy volunteers and suggesting normalization, and additional recruitment of right anterior insula, caudate head, putamen, and DLPFC. This treatment-dependent functional reorganization suggests a shift from an abnormally effortful (premotor cortex) to a more automatic (basal ganglia, anterior insula) implementation of speech-motor actions.

Aged↗
PubMed2003

[Evaluation of the primary diagnosis with a CAD-system in mammography].

PURPOSE: To assess the capability of the computer assisted detection (CAD) system to classify calcifications that are histologically verified as malignant and benign or are proven benign by magnification and follow up mammography. MATERIALS AND METHODS: Three groups of microcalcifications (MC) with and without associated masses were enrolled in the study. The cancer group included 141 screen-detected breast cancer cases. One benign group comprised 109 cases with histologically benign specimens obtained through a minimally invasive breast biopsy. A second benign group included 72 lesions with MC that appeared benign on magnification/compression views and were confirmed to be benign on follow-up mammograms over a period of at least 1.5 years. All mammograms were evaluated with a CAD system (Second Look version 3.5, CADx Medical Systems, Canada). RESULTS: CAD correctly detected 125 of 141 (89 %) cancer cases. Of the 16 false negative cases, CAD marked the location of the MC (which were associated with malignant mass) with a mass mark in 12 cases. For benign cases, CAD did not correctly mark the microcalcifications in 59 of the 109 lesions confirmed benign histologically (54.1 %) and in 39 of the 72 lesions established benign mammographically (54.2 %). Adenosis introduced the highest rate of falsely marked microcalcifications (62 %). CONCLUSION: Due to its limited specificity, CAD can still not be recommended for the primary classification of microcalcifications as malignant or benign. Nevertheless, the low false negative rate and rather high detection rate of malignant findings indicate some value of CAD for an independent second reading.

Adenocarcinoma↗
PubMed2003

Coronary stenting versus coronary bypass surgery in patients with multiple vessel disease and significant proximal LAD stenosis: results from the ERACI II study.

PURPOSE: To compare percutaneous coronary intervention (PCI) using stent implantation versus coronary artery bypass graft (CABG) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery (LAD). METHODS: 230 patients with multiple vessel disease and severe stenosis of the proximal LAD (113 with PCI, 117 with CABG). They were a cohort of patients from the randomised ERACI (Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease) II study. RESULTS: Both groups had similar baseline characteristics. There were no significant differences in 30 day major adverse cardiac events (death, myocardial infarction, stroke, and repeat procedures) between the strategies (PCI 2.7% v CABG 7.6%, p = 0.18). There were no significant differences in survival (PCI 96.4% v CABG 95%, p = 0.98) and survival with freedom from myocardial infarction (PCI 92% v CABG 89%, p = 0.94) at 41.5 (6) months' follow up. However, freedom from new revascularisation procedures (CABG 96.6% v PCI 73%, p = 0.0002) and frequency of angina (CABG 9.4% v PCI 22%, p = 0.025) were superior in the CABG group. CONCLUSION: Patients with multivessel disease and significant disease of the proximal LAD randomly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infarction at long term follow up. Repeat revascularisation procedures were higher in the PCI group.

Aged↗
PubMed2001

A biologically plausible model of associative memory which uses disinhibition rather than long-term potentiation.

Mammalian memory is commonly "explained" in terms of long-term potentiation (LTP) of excitatory synapses. However, depotentiation of inhibitory pathways (disinhibition) is also a known phenomenon in the brain. Artificial neural networks which are offered as partial models of the cerebrum traditionally encode memory by the potentiation of excitatory "synapses" in a manner which is thought of as analogous to LTP. Analysis shows that such models have seriously limited storage capacities. The models also depend on mechanisms which do not appear to be biologically plausible. This paper demonstrates that these difficulties are avoided by encoding memory by means of disinhibition rather than LTP. The resulting models are simple and plausible, though unconventional.

Association Learning↗
PubMed2001

Identification and characterization of trypanocides by functional expression of an adenosine transporter from Trypanosoma brucei in yeast.

The causative agents of sleeping sickness, Trypanosoma brucei rhodesiense and T. brucei gambiense, do not synthesize purines de novo but salvage purine bases and nucleosides from their hosts. We used yeast as an expression system for functional characterization of the trypanosomal adenosine transporter TbAT1. A selection of purine analogs and flavonoids were tested for their ability to interfere with adenosine transport, with the aims of identifying (a) trypanocidal TbAT1 substrates, and (b) inhibitors of trypanosomal purine transport. Cordycepin (3'-deoxyadenosine) was a TbAT1 substrate of high activity against T. brucei rhodesiense (IC50 0.2 nM). Inhibitors of mammalian nucleoside transport were not active, while the flavonol silibinin was a potent, noncompetitive inhibitor of TbAT1-mediated adenosine transport in yeast. Silibinin also inhibited melarsen-induced lysis of bloodstream form trypanosomes. IC50 values to T. brucei rhodesiense and to human carcinoma cells were 0.6 and 140 microM, respectively, indicating a good selectivity towards the parasites. Further studies are necessary to elucidate the effects of flavonoids on trypanosomal purine transport and their potential as trypanocides.

Adenosine↗
PubMed2001

Argentine Randomized Study: Coronary Angioplasty with Stenting versus Coronary Bypass Surgery in patients with Multiple-Vessel Disease (ERACI II): 30-day and one-year follow-up results. ERACI II Investigators.

OBJECTIVE: The purpose of this study was to compare percutaneous transluminal coronary revascularization (PTCR) employing stent implantation to conventional coronary artery bypass graft surgery (CABG) in symptomatic patients with multivessel coronary artery disease. BACKGROUND: Previous randomized studies comparing balloon angioplasty versus CABG have demonstrated equivalent safety results. However, CABG was associated with significantly fewer repeat revascularization procedures. METHODS: A total of 2,759 patients with coronary artery disease were screened at seven clinical sites, and 450 patients were randomly assigned to undergo either PTCR (225 patients) or CABG (225 patients). Only patients with multivessel disease and indication for revascularization were enrolled. RESULTS: Both groups had similar clinical demographics: unstable angina in 92%; 38% were older than 65 years, and 23% had a history of peripheral vascular disease. During the first 30 days, PTCR patients had lower major adverse events (death, myocardial infarction, repeat revascularization procedures and stroke) compared with CABG patients (3.6% vs. 12.3%, p = 0.002). Death occurred in 0.9% of PTCR patients versus 5.7% in CABG patients, p < 0.013, and Q myocardial infarction (MI) occurred in 0.9% PTCR versus 5.7% of CABG patients, p < 0.013. At follow-up (mean 18.5 +/- 6.4 months), survival was 96.9% in PTCR versus 92.5% in CABG, p < 0.017. Freedom from MI was also better in PTCR compared to CABG patients (97.7% vs. 93.4%, p < 0.017). Requirements for new revascularization procedures were higher in PTCR than in CABG patients (16.8% vs. 4.8%, p < 0.002). CONCLUSIONS: In this selected high-risk group of patients with multivessel disease, PTCR with stent implantation showed better survival and freedom from MI than did conventional surgery. Repeat revascularization procedures were higher in the PTCR group.

Aged↗
PubMed2001

The changing character of regulation: a comparison of Europe and the United States.

European and U.S. regulatory policies have changed considerably over the past 30 years. In Europe, since the mid-1980s, consumer and environmental regulation has become more politically salient and regulations have by and large become stricter. On the other hand, in the United States consumer and environmental issues have become less salient and contentious, and regulations have not become (comparatively) stricter. This apparent "flip-flop" of regulatory systems has not been analyzed in much detail to date. This perspective is an attempt to analyze some examples in which it has occurred and identifies one possible cause--namely, credibility.

Journal Article↗
PubMed2000

Role of the intracellular domain of the human type I interferon receptor 2 chain (IFNAR2c) in interferon signaling. Expression of IFNAR2c truncation mutants in U5A cells.

A human cell line (U5A) lacking the type I interferon (IFN) receptor chain 2 (IFNAR2c) was used to determine the role of the IFNAR2c cytoplasmic domain in regulating IFN-dependent STAT activation, interferon-stimulated gene factor 3 (ISGF3) and c-sis-inducible factor (SIF) complex formation, gene expression, and antiproliferative effects. A panel of U5A cells expressing truncation mutants of IFNAR2c on their cell surface were generated for study. Janus kinase (JAK) activation was detected in all mutant cell lines; however, STAT1 and STAT2 activation was observed only in U5A cells expressing full-length IFNAR2c and IFNAR2c truncated at residue 462 (R2.462). IFNAR2c mutants truncated at residues 417 (R2. 417) and 346 (R2.346) or IFNAR2c mutant lacking tyrosine residues in its cytoplasmic domain (R2.Y-F) render the receptor inactive. A similar pattern was observed for IFN-inducible STAT activation, STAT complex formation, and STAT-DNA binding. Consistent with these data, IFN-inducible gene expression was ablated in U5A, R2.Y-F, R2.417, and R2.346 cell lines. The implications are that tyrosine phosphorylation and the 462-417 region of IFNAR2c are independently obligatory for receptor activation. In addition, the distal 53 amino acids of the intracellular domain of IFNAR2c are not required for IFN-receptor mediated STAT activation, ISFG3 or SIF complex formation, induction of gene expression, and inhibition of thymidine incorporation. These data demonstrate for the first time that both tyrosine phosphorylation and a specific domain of IFNAR2c are required in human cells for IFN-dependent coupling of JAK activation to STAT phosphorylation, gene induction, and antiproliferative effects. In addition, human and murine cells appear to require different regions of the cytoplasmic domain of IFNAR2c for regulation of IFN responses.

Animals↗
PubMed2000

Sequence and diversity of DRB genes of Aotus nancymaae, a primate model for human malaria parasites.

The New World primate Aotus nancymaae is susceptible to infection with the human malaria parasite Plasmodium falciparum and Plasmodium vivax and has therefore been recommended by the World Health Organization as a model for evaluation of malaria vaccine candidates. We present here a first step in the molecular characterization of the major histocompatibility complex (MHC) class II DRB genes of Aotus nancymaae (owl monkey or night monkey) by nucleotide sequence analysis of the polymorphic exon 2 segments. In a group of 15 nonrelated animals captivated in the wild, 34 MHC DRB alleles could be identified. Six allelic lineages were detected, two of them having human counterparts, while two other lineages have not been described in any other New World monkey species studied. As in the common marmoset, the diversity of DRB alleles appears to have arisen largely by point mutations in the beta-pleated sheets and by frequent exchange of fixed sequence motifs in the alpha-helical portion. Pairs of alleles differing only at amino acid position b86 by an exchange of valine to glycine are present in Aotus, as in humans. Essential amino acid residues contributing to MHC DR peptide binding pockets number 1 and 4 are conserved or semiconserved between HLA-DR and Aona-DRB molecules, indicating a capacity to bind similar peptide repertoires. These results support fully our using Aotus monkeys as an animal model for evaluation of future subunit vaccine candidates.

Alleles↗
PubMed1998

Optimal coronary balloon angioplasty with provisional stenting versus primary stent (OCBAS): immediate and long-term follow-up results.

OBJECTIVE: This study sought to compare two strategies of revascularization in patients obtaining a good immediate angiographic result after percutaneous transluminal coronary angioplasty (PTCA): elective stenting versus optimal PTCA. A good immediate angiographic result with provisional stenting was considered to occur only if early loss in minimal luminal diameter (MLD) was documented at 30 min post-PTCA angiography. BACKGROUND: Coronary stenting reduces restenosis in lesions exhibiting early deterioration (>0.3 mm) in MLD within the first 24 hours (early loss) after successful PTCA. Lesions with no early loss after PTCA have a low restenosis rate. METHODS: To compare angiographic restenosis and target vessel revascularization (TVR) of lesions treated with coronary stenting versus those treated with optimal PTCA, 116 patients were randomized to stent (n=57) or to optimal PTCA (n=59). After randomization in the PTCA group, 13.5% of the patients crossed over to stent due to early loss (provisional stenting). RESULTS: Baseline demographic and angiographic characteristics were similar in both groups of patients. At 7.6 months, 96.6% of the entire population had a follow-up angiographic study: 98.2% in the stent and 94.9% in the PTCA group. Immediate and follow-up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group (1.95 vs. 1.5 mm; p < 0.03). However, late loss was significantly higher in the stent than the PTCA group (0.63+/-0.59 vs. 0.26+/-0.44, respectively; p=0.01). Hence, net gain with both techniques was similar (1.32< or =0.3 vs. 1.24+/-0.29 mm for the stent and the PTCA groups, respectively; p=NS). Angiographic restenosis rate at follow-up (19.2% in stent vs. 16.4% in PTCA; p=NS) and TVR (17.5% in stent vs. 13.5% in PTCA; p=NS) were similar. Furthermore, event-free survival was 80.8% in the stent versus 83.1% in the PTCA group (p=NS). Overall costs (hospital and follow-up) were US $591,740 in the stent versus US $398,480 in the PTCA group (p < 0.02). CONCLUSIONS: The strategy of PTCA with delay angiogram and provisional stent if early loss occurs had similar restenosis rate and TVR, but lower cost than primary stenting after PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1997

Effects of the CLIP fragment ACTH 20-24 on the duration of REM sleep episodes.

Substances acting upon rapid eye movement (REM) sleep or paradoxical sleep (PS) can affect the number and/or the duration of PS episodes. In the present study, we investigated the effects of the proopiomelanocortin-derived peptide CLIP (corticotropin-like intermediate lobe peptide, ACTH 18-39) and its N-terminal fragments ACTH 18-24 and ACTH 20-24 on the duration of PS episodes in rats. Intracerebroventricular injection of ACTH 20-24 caused a pronounced prolongation of PS episodes (up to 7 min duration, never seen under baseline conditions), whereas ACTH 18-24 acted in a similar way but without reaching statistical significance. We suggest that short N-terminal CLIP fragment(s) may represent endogenous hypnogenic factor(s) involved in the regulation of paradoxical sleep.

Adrenocorticotropic Hormone↗
PubMed1996

Cyclic morphiceptin analogs: cyclization studies and opioid activities in vitro.

Attempts were undertaken to develop cyclic beta-casomorphin-5 analogs with improved opioid activity profiles by deletion of the glycine residue in position 5, leading to analogs structurally related to the opioid peptide morphiceptin (H-Tyr-Pro-Phe-Pro-NH2). The tetrapeptide sequence Boc-Tyr(tBu)-D-Xaa-Phe-Yaa-OH (Xaa = Lys, Orn, A2bu; Yaa = Pro in L- or D-configuration) was used to study the influence of ring size and chirality on the yield of cyclization between the omega-amino group of Xaa and the C-terminal carboxyl group. In all cases the cyclization reaction was performed under identical experimental conditions to allow a direct comparison with regard to yield and homogeneity. The reaction products were purified by crystallization and liquid chromatography, and were characterized by HPLC, TLC, electrospray mass spectrometry and 1H-NMR spectroscopy. In none of the reactions performed with the cyclization precursors containing proline in the L-configuration could a cyclic monomer be detected, and the cyclodimer (7-9) was the exclusive product in each case. Cyclodimerization was also the favored reaction in the attempted formation of the 11-membered ring of the cyclic [D-A2bu2, D-Pro4]-morphiceptin analog 12, since only traces of the monomer were found. In the case of both the [D-Lys2, D-Pro4]-analog 10 and the [D-Orn2, D-Pro4]-analog 11, the cyclomonomer/cyclodimer ratio was about 80:20. The cyclic monomers 10 and 11 showed high opioid activity in the mu-receptor-representative guinea pig ileum assay (IC50 = 2-5 nM) and in the delta-receptor representative mouse vas deferens assay (IC50 = 50-60 nM), whereas the potency of the cyclodimers was 2-3 orders of magnitude lower in both in vitro bioassays.

Analgesics↗
PubMed1996

Analysis of the p53 and MDM-2 gene in acute myeloid leukemia.

The MDM-2 (murine double minute 2) gene codes for a cellular protein that can bind to the p53 tumor suppressor gene product, thereby functioning as a negative regulator of p53. In order to define the role of the MDM-2 gene in the pathogenesis of human acute myeloid leukemia, the expression and the sequence of the MDM-2 gene were examined in samples of bone marrow and/or peripheral mononuclear cells of 38 patients by using immunostaining, polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing. Immunohistochemical staining detected a weak accumulation of the MDM-2 protein in AML patients of FAB classification M4 and M5. RT-PCR analysis revealed a heterogeneous expression pattern of MDM-2 mRNA in AML samples of different FAB classification. An increased level of MDM-2 mRNA expression was observed in 17 of 38 AML patients when compared to normal controls. No structural changes in a 488 bp region extending from nucleotide 890 to 1378 of the MDM-2 cDNA were detected using RT-SSCP and sequence analysis. In addition, heterogeneous expression of p53 transcripts was found with the highest p53 mRNA levels in AML M4 and M5. Interestingly, there seems to be a correlation between the relative ratios of p53 and MDM-2 mRNA levels in AML M4 and M5: in 15 of 23 cases high p53 mRNA expression was directly associated with high levels of MDM-2 transcripts. An exclusively intranuclear p53 immunostaining pattern was found in 10 of 16 (58%) AML FAB M4 and M5, whereas the remaining AML samples tested were negative for p53 (0/10). Using RT-SSCP analysis and direct sequencing of the RT-PCR amplification products of p53 exon 5-8, we observed that only 1 of 38 AML patients showed a point mutation in the p53 gene. This missense mutation occurred in the evolutionary highly conserved region of p53 at codon 255 (Ile to Phe). These data indicated that structural alterations of the p53 gene do not play an important role in the initiation and progression of AML. However, abrogation of p53 tumor suppressor function due to MDM-2 overexpression may be an alternative molecular mechanism by which a subset of AMLs may escape from p53-regulated growth control.

Acute Disease↗