julilili42/papers huggingface dataset:
The provenance of "red marble" monuments from the 12th -18th centuries in Hungary
2004-07-13

“Red marble” (Liassic-Dogger nodular limestone, ammonitico rosso ) which was mined as a decorative stone, played an important role in the art of Central Europe and especially in Hungary in the past centuries. Quarries are known from the Gerecse-Mts. (Hungary), Adnet, (Austria), Menyhaza (Romania) and Verona (Italy). Determination of the provenance of the “red marble” monuments is not feasible on the basis of petrographical methods only, because the two most typical and important Central European “red marble” occurrences (the Gerecse-Mountains, Hungary and Adnet, Austria) have the same geological age and had formed in similar environments. It is possible, on the basis of stable isotope analysis, to separate the raw material from the Hungarian and Austrian quarries; it enabled us to conduct provenance studies of archaeological objects from Hungary, Upper Hungary (present Slovakia) and Transylvania (present Romania). The results are in accordance with several historical theories, but also provide additional information on the distribution of this important artistic material.
Differential roles of fibroblast growth factor‐2 during development and maintenance of auditory sensory epithelia
2004-07-13

Abstract Fibroblast growth factor‐2 (FGF2) has been postulated to be a key regulator involved in the proliferation, differentiation, and regeneration of sensory hair cells. Here we have addressed the potential functions of FGF2 during the formation and regeneration of the auditory epithelium in chicken and mice. By using viral gene transfer, based on herpes simplex type 1 virus (HSV‐1), we show that ectopically applied FGF2 drastically increases the number of cells expressing early hair cell markers during embryonic development in avians. Intriguingly, FGF2 does not stimulate cell division during this process. These data suggest that FGF2 plays a role during differentiation of sensory hair cells in avians. To address the potential functions of FGF2 during murine inner ear development, we analyzed FGF2 mouse mutants. Mice lacking FGF2 showed normal formation of the inner ear, and no abnormalities were observed at the adult stage. Moreover, FGF2 mouse mutants showed similar hearing thresholds compared with those observed in control mice before and after noise damage. Therefore, endogenous FGF2 appears not to be essential for the development or functional maintenance of the auditory organ in mammals. In light of these results, the differential roles of FGF2 in the vertebrate inner ear are discussed with respect to its previously postulated functions. © 2004 Wiley‐Liss, Inc.
PCR-Induced Sequence Alterations Hamper the Typing of Prehistoric Bone Samples for Diagnostic Achondroplasia Mutations
2004-07-14

Achondroplasia (ACH) is a skeletal disorder (MIM100800) with an autosomal dominant Mendelian inheritance and complete penetrance. Here we report the screening of ancient bone samples for diagnostic ACH mutations. The diagnostic G-->A transition in the FGFR3 gene at cDNA position 1138 was detected in cloned polymerase chain reaction (PCR) products obtained from the dry mummy of the Semerchet tomb, Egypt (first dynasty, approximately 4,890-5,050 BP [before present]), and from an individual from Kirchheim, Germany (Merovingian period, approximately 1,300-1,500 BP), both of which had short stature. However, these mutations were also reproducibly observed in four ancient control samples from phenotypically healthy individuals (false-positives), rendering the reliable molecular typing of ancient bones for ACH impossible. The treatment of a false-positive DNA extract with uracil N-glycosylase (UNG) to minimize type 2 transitions (G-->A/C-->T) did not reduce the frequency of the false-positive diagnostic ACH mutations. Recently, it was suggested that ancient DNA extracts may induce mutations under PCR. Contemporary human template DNA from a phenotypically healthy individual was therefore spiked with an ancient DNA extract from a cave bear. Again, sequences with the diagnostic G-->A transition in the FGFR3 gene were observed, and it is likely that the false-positive G-->A transitions result from errors introduced during the PCR reaction. Amplifications in the presence of MnCl(2) indicate that position 1138 of the FGFR3 gene is particularly sensitive for mutations. Our data are in line with previously published results on the occurrence of nonrandom mutations in PCR products of contemporary human mitochondrial HVRI template DNA spiked with ancient DNA extracts.
Palynological evidence for the Palaeocene evolution of the forearc basin, Indus Suture Zone, Ladakh, India
2004-07-14

Abstract The discovery of Permian, Mesozoic and Palaeocene palynomorphs from the Nindam forearc basin, exposed along the Indus Suture Zone in Ladakh, is reported. The palynomorphs are from volcanogenic sandstones and are poorly preserved, distorted and show the effects of abrasion (striation marks). The frequent occurrence of Proxapertites indicates the assemblage is at least Palaeocene in age. The Palaeocene palynomorphs and sediments were transported to the Nindam trough from nearby elevated landward regions (islands). These Palaeocene provenance areas were characterized by an estuarine, nearshore, tropical, warm‐humid environment and were situated at equatorial palaeolatitudes. However, the occurrence of Permian and Mesozoic palynomorphs in the assemblage indicates that the Late Palaeozoic and Mesozoic Tethyan sedimentary rocks exposed along the northern margin of the Indian plate were redeposited into the tectonically active Cretaceous–Palaeocene trench–subduction complex that existed between the Indian and the Asian plates until the collision took place at ∼50–60 Ma.
A Constitutively Active Dioxin/Aryl Hydrocarbon Receptor Promotes Hepatocarcinogenesis in Mice
2004-07-15

Abstract The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding enzymes involved in drug metabolism. Known ligands include polycyclic aromatic hydrocarbons, certain polychlorinated biphenyls, and the polyhalogenated dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin. Both polyhalogenated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin are potent promoters of rodent hepatocarcinogenesis in two-stage initiation-promotion experiments. Although several lines of evidence indicate the involvement of the AhR in toxic effects mediated by polyhalogenated biphenyls and dioxins, its involvement in tumor promotion has not been unequivocally proven. In the present study, a transgenic mouse line expressing a constitutively active AhR (CA-AhR) has been used to investigate the role of the AhR in hepatocarcinogenesis. Male AhR wild-type and CA-AhR-transgenic B6C3F1-mice were treated with a single injection of the hepatocarcinogen N-nitrosodiethylamine at 6 weeks of age and were subsequently kept untreated on control diet. Thirty five weeks after carcinogen treatment, mice were sacrificed, and the prevalence and multiplicity of liver tumors were determined. Whereas only 1 small liver tumor was observed in 15 AhR-wild-type mice, 19 tumors (two &amp;gt;1 cm in diameter) were present in 18 CA-AhR-transgenic mice. This result demonstrates the oncogenic potential of the activated AhR and implicates an important role of the receptor in promotion of hepatocarcinogenesis. A microarray-based gene expression-profiling analysis revealed down-regulation in the liver of CA-AhR-transgenic mice of a cluster of genes encoding heat shock proteins, including GRP78/BiP, Herp1, Hsp90, DnaJ (Hsp40) homologue B1, and Hsp105, which are important for protein folding and quality control.
Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis
2004-07-15

Abstract A prominent hallmark of Alzheimer's disease pathology is cerebral amyloidosis. However, it is not clear how extracellular amyloid‐β peptide (Aβ) deposition and amyloid formation compromise brain function and lead to dementia. It has been argued that extracellular amyloid deposition is neurotoxic and/or that soluble Aβ oligomers impair synaptic function. Amyloid deposits, by contrast, may affect diffusion properties of the brain interstitium with implications for the transport of endogenous signalling molecules during synaptic and/or extrasynaptic transmission. We have used diffusion‐weighted magnetic resonance imaging to study diffusion properties in brains of young (6‐month‐old) and aged (25‐month‐old) APP23 transgenic mice and control littermates. Our results demonstrate that fibrillar amyloid deposits and associated gliosis in brains of aged APP23 transgenic mice are accompanied by a reduction in the apparent diffusion coefficient. This decrease was most pronounced in neocortical areas with a high percentage of congophilic amyloid and was not significant in the caudate putamen, an area with only modest and diffuse amyloid deposition. These findings suggest that extracellular deposition of fibrillar amyloid and/or associated glial proliferation and hypertrophy cause restrictions to interstitial fluid diffusion. Reduced diffusivity within the interstitial space may alter volume transmission and therefore contribute to the cognitive impairment in Alzheimer's disease.
Direct toxic effect of cytostatic drugs on erythrocytes as possible reason for chemotherapy-induced anemia
2004-07-15

781 Background: So far suppression of the bone marrow has been claimed to be the main reason of chemotherapy-induced anaemia. However assuming an average duration of red blood cell (RBC) lifetime of 120 days, anemia can not be explained only by the suppression of bone marrow. It may be supposed that during the course of chemotherapy (CHT) existing RBC perish through oxidation processes which lead to a decrease of deformability and finally to the elimination of these RBC. This mechanism may well be one reason for CHT-induced anemia. This study was carried out to investigate whether there is any influence of CHT on RBC-deformability and whether there is a correlation between RBC-deformability and anemia in patients receiving CHT. Methods: 51 patients with breast or ovarian cancer treated with regimens like Epirubicin/Cyclophosphamide or taxane- and platin-based combinations were included in this study. The Hb was determined before the application of CHT in each cycle. The deformablility of RBC was measured by laser diffractoscopy before and 2h after the application of the cytostatic drugs in each cycle. Results: It could be shown, that both Hb and deformability of RBC was decreased by the employed CHT-regimens (Table 1). In all cycles 2 h after the administration of CHT a reduction of deformability of RBC was already measurable. There was a correlation between the Hb reduction and the decrease of the deformability of RBC. In addition, after the 4th cycle CHT the degree of the decrease of RBC-flexibilty was significantly associated with the Hb reduction. Conclusions: Hb reduction during CHT might not only be the consequence of myelosuppression. During the course of CHT existing RBC perish because of decreasing deformability. Analysis of RBC-deformability shortly after the first application of cytostatic drugs might therefore be an instrument to predict patients developing severe anemia during CHT. No significant financial relationships to disclose.
Primary malignant sarcomas of the heart and great vessels - a single center experience
2004-07-15

9044 Background: Sarcomas of the heart and the great vessels are very rare entities. The most common subtypes included leiomyo- and angiosarcoma. Prognosis is very poor because of locally advanced or metastatic stage at diagnosis. Methods: Between 6/2001 and 10/2003 12 patients (pts) have been identified in the sarcoma registry of Tuebingen University. Results: Median age was 43 years (22 –72). All pts were symptomatic with reduction of vitality, anorexia, dyspnoea, or neurological symptoms at the time of reception. Tumors were located in atrium [(n=5), left (3)/right (2)], Art. pulmonalis (n=3), Aorta (n=2), pericardium or left chamber, (n=1 each). Six pts presented with localized disease and 5 pts underwent curative intended resection (n=1 considered as irresectable). Six pts had advanced disease including brain mets (4 pts), lymph nodes involvement (2), lung (3) and liver mets (2). Five of these 6 pts underwent palliative resection to relieve the physiologic effects of the tumor. Three out of 5 pts with curative intended surgery have subsequently developed recurrence within 6, 8 and 25 mos despite adjuvant treatment. Palliative chemotherapy including adriamycin and ifosfamide has been applied in 7 pts and 4 pts attained some response to treatment (n=1 PR, n=3 SD). Palliative radiation included 3 pts with brain metastases and a single pt with progressive primary tumor. After a median follow up 13 mos (2 –28) 2 pts had NED, 3 pts are alive with disease and 7 pts have died due to tumor progression. Conclusions: Pts with primary sarcomas of the heart and the great vessels were often of young age, and half of them presented with locally or distant advanced disease. These pts should preferentially be referred to a tertiary Cancer Center immediately after diagnosis without preceding treatment attempts. Although the majority of pts cannot be treated curatively due to the delay in diagnosis, an optimized treatment approach including neoadjuvant chemo-/radiotherapy might enhanced the rate of complete resection depending on the histological subtype and responsiveness to treatment. No significant financial relationships to disclose.
Comparison of high-dose methotrexate (HDMTX) toxicity in elderly and younger patients (pts) with primary central nervous system lymphoma (PCNSL)
2004-07-15

8041 Background: A reduced dose of HDMTX is often given to elderly pts because of the risk of toxicity. This may result in loss of treatment efficacy and further prognosis impairment in this poor prognosis population. Methods: HDMTX toxicity was prospectively evaluated in an ongoing randomized multicenter phase IV study in PCNSL pts. In 154 pts, an analysis of toxicity according to the pts' age was performed. Median age was 61 years (yrs). Sixty-five pts were ≤ 60 yrs and had a median Karnofsky performance score (KPS) of 80, 89 pts were > 60 yrs and had a median KPS of 70. HDMTX (4 g/m2 per course) was administered as a 4-hour intravenous (IV) infusion on day 1 every 2 weeks for a maximum of 6 courses and was accompanied by IV hydration, urinary alkalinization, and leucovorin rescue at a dose of 30 mg IV every 6 hours after 24 hours of HDMTX infusion. HDMTX dose reduction was performed according to creatinine clearance values evaluated before each treatment course: the percentage of dose reduction equaled the percentage of creatinine clearance value below 100 ml/min. Results: Toxicity was generally mild to moderate. No statistically significant differences in frequency and severity of toxicity between pts ≤ 60 and > 60 yrs were noted (table). No therapy-related deaths occurred. Dose reduction due to decrease in creatinine clearance was much more frequent in pts > 60 yrs than in those ≤ 60 yrs (43.9 % versus 17.5 %, p = 0.001). Conclusions: HDMTX is safe regardless of age when dose reduction is performed according to creatinine clearance. Dose reduction solely according to age does not appear to be justified. No significant financial relationships to disclose.
One week on/one week off regimen of temozolomide for recurrent glioblastoma: A phase II study
2004-07-15

1536 Background:Median survival for patients with glioblastoma is 12 months. Patients progressing after cytoreductive surgery, radiotherapy and nitrosourea-based adjuvant chemotherapy experience a median survival of 4–6 months. There is no standard treatment for recurrent malignant glioma. Temozolomide has shown activity in phase II studies of malignant gliomas and a phase III study of metastatic malignant melanoma. It is generally administered orally at 200 mg/m2 body surface area in a five-day every 28 days schedule. Methods:Twentyone patients with recurrent or progressive glioblastoma were enrolled in a prospective, unicenter trial to determine whether a one week on/one week off regimen of temozolomide is feasible and effective as a salvage therapy. Chemotherapy consisted of temozolomide at 150 mg/m2 on days 1 to 7 and days 15 to 21 of 28 days treatment cycles. Results:There was no specific treatment-related neurotoxicity, but 3 of 21 patients (14%) had to discontinue chemotherapy because of WHO IV hematological toxicity. There were two partial responses (10%), 17 patients (81%) had stable disease according to MacDonald criteria. The median progression-free survival is 5 months, and the progression-free survival rate at 6 months is 43%. The median overall survival from diagnosis has not yet been reached, but will be more than 16 months. Conclusions:The schedule used in the present study is a feasible and effective treatment of recurrent glioblastoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ESSEX Pharma; Thomas-Dehler-St ESSEX Pharma; Thomas-Dehler-St
Consequences of expression and release of MIC molecules by malignant cells
2004-07-15

9708 Background: NKG2D-ligands (NKG2DL) mark malignant cells for recognition by cytotoxic lymphocytes via the immunoreceptor NKG2D. The human NKG2DL MICA and MICB are expressed on tumors of epithelial and hematopoietic origin, and recently we reported that MICA is released by tumor cells in a soluble form (sMICA) and can be detected in sera of patients (Salih et al., J. Immunol. 169: 4098. 2002). NKG2D-mediated immune responses are critically dependent on the expression levels of NKG2DL; therefore, reduction of MIC protein expression by release from the cell surface would potentially reduce immunogenicity of tumors. In addition, it has been reported that sMICA downregulates NKG2D expression leading to functional impairment of cytotoxic lymphocytes (Nature 17;419: 734 2002). Methods: Tumor cells were cultured in the presence of a metalloprotease-inhibitor, then cells were analysed for MICB surface expression by FACS and culture supernatants were investigated by ELISA for soluble MICB (sMICB). In addition, sera from patients with colon carcinoma, rectum carcinoma, stomach carcinoma and AML were investigated for sMICB, and the results were compared to levels of sMICA in these patients. NK cells were cultured in the presence or absence of soluble or cell bound MIC protein and the effects on NKG2D surface expression were followed by FACS. Results: We found high levels of sMICB in sera of tumor patients compared to healthy controls; release of sMICB from tumor cells is blocked by inhibition of metalloproteinases, concomitantly causing accumulation of MICB on the cell surface. MIC-protein causes downregulation of surface NKG2D on NK in cell-bound, but not in soluble form. Furthermore, we evaluated both sMICA and sMICB as tumor markers and demonstrate significant differences in sMICA or sMICB levels among various tumor entities. Conclusions: Shedding of MICB by tumor cells may modulate NKG2D mediated tumor immune surveillance. Determination of soluble MIC protein levels may be implemented as an diagnostic marker in patients with malignancies. Further prospective studies are currently being conducted addressing the value of each MIC molecule as a tumor marker in different tumor entities. No significant financial relationships to disclose.
Induction of apoptosis by flavopiridol (FP) independent of a cell cycle arrest in germ cell tumor (GCT) cell lines
2004-07-15

9712 Background: GCTs are highly sensitive to cisplatin-based chemotherapy. The inability to arrest the cell cycle at the G1/S-check-point due to a lack of retinoblastoma gene product (RB) has been suggested as an explanation. FP, an inhibitor of cyclin dependent kinases, causes cell cycle arrest or apoptosis depending on the relation of transcription factor E2F1 to RB. Methods: The effect of FP was evaluated in GCT-derived cell lines 2102EP, NT2, and NCCIT in comparison with other solid tumor cell lines (SKOV, MCF7, HeLa) using the MTT-assay. Cell cycle progression and induction of apoptosis were followed by flow cytometry and immunoblot analysis of PARP-cleavage. Results: FP did not affect cell cycle and proliferation of GCT cell lines at sublethal doses. Cell death occurred independent of cell cycle progression at doses well beneath plasma concentrations in clinical studies. The IC50 was 5fold lower for the GCT cell lines (60/60/70 nM) than for the other cell lines tested (350/280/300 nM). Sensitivity for FP did not correlate with that for cisplatin. Flow cytometry and immunoblot for PARP indicated apoptotic cell death induced by FP. Synergism between cisplatin or paclitaxel and FP was not observed. Conclusion: The data suggest significant antitumor activity of FP in GCT. GCT derived cell lines were far more responsive of FP than the cells derived from other solid tumor models. No cross resistance between FP and cisplatin was observed. In contrast to other cell lines tested, GCT derived cell lines did not show cell cycle arrest after exposure to FP, possibly due to the lack of RB-expression. However, already at low concentrations, apoptosis was induced unrelated to cell cycle progression. A clinical trial evaluating the single agent activity of FP in patients with cisplatin-refractory GCTs would be warranted. No significant financial relationships to disclose.
Prediction of tumor cell dissemination in primary breast cancer by tumor biological and clinicopathological factors
2004-07-15

661 Background: The presence of disseminated tumor cells in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis and may therefore be related with aggressive breast cancer and high tumor load as indicated by tumorbiological and clinicopathological features. The aim of this study was to identify those features related to the presence and number of disseminated tumor cells in BM. Methods: Clinical data from 360 primary breast cancer patients who underwent surgery and received a bone marrow aspiration between 2001 and 2003 at the Dept. of Gyn/OB, University of Tübingen, Germany were analyzed. Tumorbiological features of the primary tumor including HER2, p53, ki-67, bcl-2, estrogen and progesterone receptor status as well as clinicopathological factors including histology, menopausal status, lymph node status, tumor size and grade were studied for their association with BM involvement by univariate (Chi-squared test) and multivariate analysis (logistic regression). The relationship between the number of disseminated tumor cells and tumorbiological and clinicopathological factors were evaluated by Mann-Whitney-U-test. Results: 142 of 360 (39%) of the primary breast cancer patients had disseminated tumor cells in the BM. The number of tumor cells in bone marrow-positive patients ranged from 1 to 35 tumor cells. Histological grade, p53, estrogen receptor status and ki-67 were significantly related to BM involvement and the number of disseminated tumor cells. No association could be observed for all other factors. The multivariate analysis revealed that grade (OR: 1.9, 95%-CI:1.1–3.5) and estrogen receptor status (OR: 2,5, 95%-CI: 1.4–4.4) were the only independent determinants for BM involvement. Conclusion: Tumor grade and estrogen receptor status were the only reliable indicators of the likelihood of tumor cell dissemination in BM. The presence of disseminated tumor cell in the BM was not influenced by tumor load as reflected by tumor size and lymph node status. No significant financial relationships to disclose.