julilili42/papers huggingface dataset:
Cationic cell-penetrating peptides interfere with TNF signalling by induction of TNF receptor internalization
2005-08-01

Cationic cell-penetrating peptides (CPPs) have been used widely as delivery vectors for the import of molecules that otherwise do not cross the plasma membrane of eukaryotic cells. In this work, we demonstrate that the three cationic CPPs, Antennapedia homeodomain-derived peptide (Antp), nona-arginine and Tat-derived peptide, inhibit tumour necrosis factor (TNF)-mediated signal transduction. This inhibition is based on the downregulation of TNF receptors at the cell surface by induction of internalization. In contrast to TNF-dependent receptor internalization, no receptor activation occurs. The receptor downregulation is not restricted to the CPPs. Remarkably, the HIV-1 Tat protein itself also induces the internalization of TNF receptors. The dynamin dependence of the internalization, as well as the fact that epidermal growth factor receptors are also internalized, suggest a general induction of clathrin-dependent endocytosis as the mechanism of action. The significance of these findings for the use of cationic CPPs in the import of bioactive peptides is demonstrated here using a conjugate consisting of Antp and a Smac protein-derived cargo peptide. The cargo alone, when introduced into cells by electroporation, enhanced TNF-induced apoptosis by inhibiting the anti-apoptotic action of IAPs (inhibitor of apoptosis proteins). For the Antp-Smac conjugate at concentrations below 40 μM the inhibitory effect of the Antp peptide compensated for the pro-apoptotic activity of the cargo, and led to the protection of cells against TNF-mediated apoptosis. These data provide important new information for the use of cationic CPPs for the cellular delivery of bioactive molecules.
Creatine Supplementation Normalizes Mutagenesis of Mitochondrial DNA as Well as Functional Consequences
2005-08-01

Mutations of mitochondrial (mt) DNA play a role in neurodegeneration, normal aging, premature aging of the skin (photoaging), and tumors. We and others could demonstrate that mtDNA mutations can be induced in skin cells in vitro and in normal human skin in vivo by repetitive, sublethal ultraviolet (UV)-A-irradiation. These mutations are mediated by singlet oxygen and persist in human skin as long-term biomarkers of UV exposure. Although mtDNA exclusively encodes for the respiratory chain, involvement of the energy metabolism in mtDNA mutagenesis and a protective role of the energy precursor creatine have thus far not been shown. We assessed the amount of a marker mutation of mtDNA, the so-called common deletion, by real-time PCR. Induction of the common deletion was paralleled by a measurable decrease of oxygen consumption, mitochondrial membrane potential, and ATP content, as well as an increase of matrix metalloproteinase-1. Mitochondrial mutagenesis as well as functional consequences could be normalized by increasing intracellular creatine levels. These data indicate that increase of the energy precursor creatine protects from functionally relevant, aging-associated mutations of mitochondrial DNA.
Volume Measurement of Cerebral Blood Flow: Assessment of Cerebral Circulatory Arrest
2005-08-01

Early confirmation of cerebral circulatory arrest is of decisive importance if the patient is a potential organ donor. CBF volume measurement allows confirming the arrest of cerebral circulation even in patients without a patent acoustic bone window for TCCD. Because the critical lower threshold for survival appears to lie at 200 ml/min, bedside monitoring of CBF volume in neurointensive care patients may indicate a therapeutic window before irreversible circulatory arrest occurs.
Detection of Melanoma Cells Displaying Multiple Genomic Changes in Histopathologically Negative Sentinel Lymph Nodes
2005-08-01

Abstract Purpose: Improved detection of early-disseminated melanoma cells may eventually translate into more effective patient care. We present a novel strategy for detection of melanoma cells in sentinel lymph nodes and confirm their malignant descent by genomic characterization. Experimental Design: In sentinel lymph nodes from 358 melanoma patients, we prospectively compared the rates of tumor cell detection between immunocytochemistry using HMB45 and Melan A antibodies on disaggregated lymph node samples and standard histopathology (H&amp;E staining and immunostaining on tissue sections). Immunocytochemical melanoma cell detection was controlled by testing lymph node samples from 59 nonmelanoma patients and by isolation and comparative genomic analysis of 30 antigen-positive cells. Results: Of the 358 patients, 43 (12%) were positive by standard histopathology, whereas HMB45 immunocytochemistry detected 159 of 358 (44%) positive patients. None of the control samples reacted with the HMB45 antibody. Reexamination of samples that were classified as negative by histopathology revealed that extensive serial sectioning would be necessary to achieve sensitivity similar to HMB45 immunocytochemistry. Interestingly, both the number of immunocytochemically positive samples and the number of positive cells in the sentinel node correlated with the thickness of the primary tumor (r = 0.34; P = 0.001 and P &amp;lt; 0.0001, respectively). Twenty-four of 30 isolated immunocytochemically positive cells (80%) displayed chromosomal aberrations, some of which were isolated from histopathologically negative nodes. Conclusion: Immunocytochemical detection of melanoma cells in sentinel lymph nodes is superior to standard histopathology. It remains to be determined whether the detection and genomic characterization of isolated melanoma cells in sentinel lymph nodes will provide relevant prognostic information.
HERODOTUS’ AND PLINY'S EMBALMING MATERIALS IDENTIFIED ON ANCIENT EGYPTIAN MUMMIES*
2005-08-01

Unused ancient Egyptian embalming material unearthed at Deir el‐Bahari ( c. 1500 bc ) shed new light on the potential preparation methods for various embalming materials in Pharaonic Egypt. Analyses revealed the presence of phenols, guaiacols, naphthalenes and sesquiterpenoids. These components were attributed to a wood tar oil produced by a dry distillation or smouldering process from the true cedar tree. The preservation effects were elucidated at the molecular level. Bone alkaline phosphatase, an enzyme that is tightly bound in deeper regions of the bone mineral, served as a marker to reveal the efficacy of the investigated compounds. A very similar embalming material was extracted from a Ptolemaic torso (340 ± 170 bc ), showing powerful bactericidal and fungicidal activity on the mummified tissue and bones. Here, we show that both the unused and the used embalming materials are in striking accordance with Pliny's description of liquid ‘ cedrium ’, with the abundantly present guaiacol proving the most effective conserving compound.
Targeted Cancer Therapy Using Radiolabeled Monoclonal Antibodies
2005-08-01

Radioimmunotherapy (RIT) combines the advantages of targeted radiation therapy and specific immunotherapy using monoclonal antibodies. RIT can be used either to target tumor cells or to specifically suppress immunocompetent host cells in the setting of allogeneic transplantation. The choice of radionuclide used for RIT depends on its distinct radiation characteristics and the type of malignancy or cells targeted. Beta-emitters with their lower energy and longer path length are more suitable to target bulky, solid tumors whereas α-emitters with their high linear energy transfer and short path length are better suited to target hematopoietic cells (normal or malignant). Different approaches of RIT such as the use of stable radioimmunoconjugates or of pretargeting strategies are available. Encouraging results have been obtained with RIT in patients with hematologic malignancies. The results in solid tumors are somewhat less favorable but new strategies for patients with minimal residual disease using adjuvant and locoregional treatment are evolving. This report outlines basic principles of RIT, gives an overview of available radionuclides and radioimmunoconjugates, and discusses clinical results with special emphasis on their use in hematologic malignancies including use in conditioning regimens for bone marrow transplantation.
Glucagon-Like Peptide-1 as a Treatment Option for Type 2 Diabetes and Its Role in Restoring Beta-Cell Mass
2005-08-01

The "incretin effect" describes the enhanced insulin response from orally ingested glucose compared with intravenous glucose leading to identical postprandial plasma glucose excursions. It makes up to 60% of the postprandial insulin secretion but is diminished in type 2 diabetes. Gastrointestinal hormones promoting the incretin effect are called incretins. Glucagon-like peptide- 1 (GLP-1) is an important incretin. In vitro and animal data have demonstrated that GLP-1 increases beta-cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets. The improvement of beta-cell function can be indirectly observed from the increased insulin secretory capacity of humans receiving GLP-1 or incretin mimetics that act like GLP-1. Furthermore, GLP-1 inhibits glucagon secretion and rarely causes hypoglycemia. It may represent an attractive therapeutic method for type 2 diabetes because of its multiple effects, including a slowing of gastric emptying and the simulation of satiety by acting as a transmitter in the CNS. Native GLP-1 is degraded rapidly upon intravenous or subcutaneous administration and is therefore not feasable for routine therapy. Long-acting GLP-1 analogs (e.g., Liraglutide [Novo Nordisk, Copenhagen, Denmark]) and exenadin-4 (Exenatide [Eli Lilly, Indianapolis, IN]) that are resistant to degradation, called "incretin mimetics," are being investigated in clinical trials. Dipeptidyl peptidase IV inhibitors (e.g., Vildagliptin [Novartis, Basel, Switzerland]) that inhibit the enzyme responsible for incretin degradation are also under study.
Longitudinal clinical and serological survey of abdominal angiostrongyliasis in Guaporé, southern Brazil, from 1995 to 1999
2005-08-01

Abdominal angiostrongyliasis is a zoonotic infection caused by Angiostrongylus costaricensis, a nematode with an intra-vascular location in the mesentery. Our objective was to address several aspects of the natural history of this parasitosis, in a longitudinal clinical and seroepidemiological study. A total of 179 individuals living in a rural area with active transmission in southern Brazil were followed for five years (1995-1999) resulting in yearly prevalence of 28.2%, 4.2%, 10%, 20.2% and 2.8% and incidences of 0%, 5.9%, 8% and 1.5%, respectively. Both men and woman were affected with higher frequencies at age 30-49 years. In 32 individuals serum samples were collected at all time points and IgG antibody reactivity detected by ELISA was variable and usually persisting not longer than one year. Some individual antibody patterns were suggestive of re-infection. There was no association with occurrence of abdominal pain or of other enteroparasites and there was no individual with a confirmed (histopathologic) diagnosis. Mollusks were found with infective third-stage larvae in some houses with an overall prevalence of 16% and a low parasitic burden. In conclusion, abdominal angiostrongyliasis in southern Brazil may be a frequent infection with low morbidity and a gradually decreasing serological reactivity.
Potential Applications of Flat-Panel Volumetric CT in Morphologic, Functional Small Animal Imaging
2005-08-01

Noninvasive radiologic imaging has recently gained considerable interest in basic and preclinical research for monitoring disease progression and therapeutic efficacy. In this report, we introduce flat-panel volumetric computed tomography (fpVCT) as a powerful new tool for noninvasive imaging of different organ systems in preclinical research. The three-dimensional visualization that is achieved by isotropic high-resolution datasets is illustrated for the skeleton, chest, abdominal organs, and brain of mice. The high image quality of chest scans enables the visualization of small lung nodules in an orthotopic lung cancer model and the reliable imaging of therapy side effects such as lung fibrosis. Using contrast-enhanced scans, fpVCT displayed the vascular trees of the brain, liver, and kidney down to the subsegmental level. Functional application of fpVCT in dynamic contrast-enhanced scans of the rat brain delivered physiologically reliable data of perfusion and tissue blood volume. Beyond scanning of small animal models as demonstrated here, fpVCT provides the ability to image animals up to the size of primates.
Archaeology and Prevalence of Paget's Disease
2005-08-01

To the Editor: Rogers et al.1 presented data on the prevalence of Paget's disease of bone (PDB) in an archeological population comprising 2770 individuals from northeast England in the Journal. Their study showed an increase in the rate of the disease over time. In March 2004 Waldron2 concluded after recalculation of the data from Rogers et al.1 that the disease prevalence had not changed over the 1500 years covered by these burials. We now finished a study on a large skeletal assemblage comprising >8500 individuals from central Europe that provided the opportunity to examine the prevalence of PDB over a period of five millennia of human history (5600 BP to 1500 AD). The prevalence of PDB in our archeological population was only 0.03% (entry criteria as described in ref. 1), with no occurrence of pagetic bones before 1400 AD. We consider this a valid estimation, because PDB cannot be overlooked in skeletal material and because it is based on the greatest number of skeletal remains examined to date. Although PDB was first described in 1877 by the British surgeon Sir James Paget (1814–1899),3 PDB is in fact a very old condition with few (but controversially discussed) cases being known from the archeological record.1 Today, it is a fairly common disease with ∼1–3% in middle and advanced adulthood being affected.4 The infrequency of PDB in our study collection remarkably contrasts the figures of today's disease prevalence. Despite environmental factors playing a role in the etiology of PDB, we favor the explanation that the late-onset and slowly developing manifestation of PDB prevented people in former times from affliction. Whereas only a few centuries ago the average life expectancy was <30 years, it is now at >75 years in industrialized countries. In our subset of specimens dating from the early Middle Ages, we determined a percentage of only 26% being >40 years (40–52 years maximum), whereas for modern populations, this figure is 84%. Consistently, reports of low prevalence of PDB suggest that the disease is uncommon in Africa, where people die earlier because of unfavorable living conditions.5 The longer human life spans, including a prominent proportion of elderly, enables PDB to appear more frequently nowadays. Our study thus contrasts the recent conclusion published by Waldron,2 but may grossly illustrate spatial and temporal differences in the disease etiology of PDB.
Market Structure and Innovation Races / Marktstruktur und Innovationsrennen
2005-08-01

Summary Based on an extended game-theoretic innovation-race model, we derive some Schumpeterian hypotheses of the impact of technological rivalry, market power, technological opportunities and demand expectations on the timing of product and process innovations. Using innovation data at the firm level in the German industrial sector, we estimate various versions of an econometric specification of the model with dichotomous innovation data by using a univariate binary probit model with qualitative regressor variables estimated applying indirect inference. Our empirical results are consistent with the derived hypotheses that intense rivalry, favorable technological opportunities and high demand expectations spur innovative activity, while the effect of market power is ambiguous.
seeing and talking: whorf wouldn't be satisfied
2005-08-01

although steeles &amp; belpaeme's (s&amp;b) results may be useful for development of technical devices, their significance for behavioral sciences is very limited. this is because the question the authors asked was “why do people use similar words in a similar way?” rather than “how can similar words stand for similar experience?” the main problem is not shared word usage, but shared references.
Reconstructive Urology
2005-08-01

Purpose: Neurogenic bladder is a major problem for children with spina bifida.Despite rigorous pharmacological and surgical treatment, incontinence, urinary tract infections and upper tract deterioration remain problematic.We have previously demonstrated the ability to establish surgically a skin-central nervous system-bladder reflex pathway in patients with spinal cord injury with restoration of bladder storage and emptying.We report our experience with this procedure in 20 children with spina bifida.Materials and Methods: All children with spina bifida and neurogenic bladder underwent limited laminectomy and a lumbar ventral root (VR) to S3 VR microanastomosis.The L5 dorsal root was left intact as the afferent branch of the somatic-autonomic reflex pathway after axonal regeneration.All patients underwent urodynamic evaluation before and after surgery.Results: Preoperative urodynamic studies revealed 2 types of bladder dysfunction-areflexic bladder (14 patients) and hyperreflexic bladder with detrusor external sphincter dyssynergia (6).All children were incontinent.Of the 20 patients 17 gained satisfactory bladder control and continence within 8 to 12 months after VR microanastomosis.Of the 14 patients with areflexic bladder 12 (86%) showed improvement.In these cases bladder capacity increased from 117.28 to 208.71 ml, and mean maximum detrusor pressure increased from 18.35 to 32.57 cm H2O.Five of the 6 patients with hyperreflexic bladder demonstrated improvement, with resolution of incontinence.Urodynamic studies in these cases revealed a change from detrusor hyperreflexia with detrusor external sphincter dyssynergia and high detrusor pressure to nearly normal storage and synergic voiding.In these cases mean bladder capacity increased from 94.33 to 177.83 ml, and post-void residual urine decreased from 70.17 to 23.67 ml.Overall, 3 patients failed to exhibit any improvement.Conclusions: The artificial somatic-autonomic reflex arc procedure is an effective and safe treatment to restore bladder continence and reverse bladder dysfunction for patients with spina bifida.
Tracheal Surgery in Children
2005-08-01

With respect to therapy of congenital and post-intubation tracheal stenosis, four types should be distinguished. Each of these types requires an adequate surgical procedure. The most important postoperative problem in tracheal surgery is the development of granulation tissue. However, the pathogenesis of granulation is still unknown.
Investigation of the Interface Between Biological Cell Tissue and Hard Substrate Materials using CrossBeam Technology
2005-08-01

Journal Article Investigation of the Interface Between Biological Cell Tissue and Hard Substrate Materials using CrossBeam Technology Get access P Gnauck, P Gnauck Carl Zeiss SMT,Germany Search for other works by this author on: Oxford Academic Google Scholar C Burkhardt, C Burkhardt NMI,Germany Search for other works by this author on: Oxford Academic Google Scholar H Wolburg, H Wolburg University of Tuebingen,Germany Search for other works by this author on: Oxford Academic Google Scholar W Nisch W Nisch NMI,Germany Search for other works by this author on: Oxford Academic Google Scholar Microscopy and Microanalysis, Volume 11, Issue S02, 1 August 2005, Pages 800–801, https://doi.org/10.1017/S1431927605501843 Published: 01 August 2005
PURE GOLD OF PSYCHOANALYSIS OR PURE CHEMISTRY? HOW CAN WE HANDLE THE COUNTER‐TRANSFERENCE AND THE PSYCHOANALYST'S SUPER‐EGO CONFLICTS IN COMBINED TREATMENT?1
2005-08-01

The use of drugs during psychoanalysis as well as the psychoanalytical treatment of patients who need psychopharmacological medication raise a whole series of problems that are also the subject of controversial discussion. Nevertheless, the body of literature available on this topic is still quite small. Medication is invariably an outside parameter that is introduced into the psychoanalysis and it can cause a blind spot in the psychoanalytic treatment. On the other hand, as we are treating severely disturbed patients, we are confronted with a growing necessity to introduce medication into the psychoanalytic setting. The paper discusses the related conflicts of the psychoanalyst and shows in a case report how an analytic stance can go hand in hand with adequate medication. The paper argues that we have to accept the state of the art in psychiatry and at the same time continue to talk about medication in terms of psychological processes even though it poses a conflict and is also a threat to our narcissistic equilibrium.
Bank Supervision and Corruption in Lending
2005-08-01

Which commercial bank supervisory policies ease or intensify the degree to which bank corruption is an obstacle to firms raising external finance?Based on new data from more than 2,500 firms across 37 countries, this paper provides the first empirical assessment of the impact of different bank supervisory policies on firms' financing obstacles.We find that the traditional approach to bank supervision, which involves empowering official supervisory agencies to directly monitor, discipline, and influence banks, does not improve the integrity of bank lending.Rather, we find that a supervisory strategy that focuses on empowering private monitoring of banks by forcing banks to disclose accurate information to the private sector tends to lower the degree to which corruption of bank officials is an obstacle to firms raising external finance.In extensions, we find that regulations that empower private monitoring exert a particularly beneficial effect on the integrity of bank lending in countries with sound legal institutions.
Clearance of Chlamydia pneumoniae Infection in H‐2 Class I–/– Human Leucocyte Antigen‐A2.1 Monochain Transgenic Mice
2005-08-01

Abstract CD8 + T cells have been suggested to play an important role in protective immunity against pulmonary Chlamydia pneumoniae infection in mice. Moreover, several classical major histocompatibility complex class I – restricted cytotoxic CD8 + T lymphocytes (CTL) specific for C. pneumoniae – derived peptides have been identified. Here, we studied the outcome of C. pneumoniae infection in human leucocyte antigen (HLA)‐A2.1 transgenic mice (HHD mice) that are only able to express a classical human class I molecule (HLA‐A2.1). C. pneumoniae infection was self‐restricted in HHD mice which were able to develop specific immune responses and a protective immunity against a subsequent rechallenge in a manner comparable to wildtype mice. Furthermore, accumulation of functional and C. pneumoniae‐ specific T cells to the site of infection was detected after challenge. Antigen processing and HLA‐A2.1‐dependent presentation was studied by immunizing the HHD mice with chlamydial outer protein N (CopN). Isolation of a peptide‐specific CTL line from the CopN‐immunized mice suggests that the HLA‐A2.1 molecule can support the development of CTL response against a chlamydial protein in mice. These findings suggest that the transgenic mouse model can be used for further characterization of the HLA‐A2.1‐restricted CD8 + T‐cell response during C. pneumoniae infection and for identification of CD8 epitopes from chlamydial antigens.