julilili42/papers huggingface dataset:
Genesis, sequestration and survival of Plasmodium falciparum gametocytes: parameter estimates from fitting a model to malariatherapy data
2001-09-01

Plasmodium falciparum malaria is one of mankind's main killers. Part of the parasite's life-cycle is spent in human blood, mainly as asexual stages. A fraction of the asexual parasites develops into gametocytes (gamete precursors) while sequestered in deep tissues. After re-entering the circulation, gametocytes can be picked up by a mosquito to continue the parasite's life-cycle. We present estimates of the conversion probability from asexual parasites to circulating gametocytes and of the gametocytes' sequestration and circulation times, obtained for the first time by fitting a dynamic model to individual patients' histories (daily records of 113 neurosyphilitic patients undergoing malariatherapy). The model assumes that the conversion probability can vary among the successive waves of asexual parasitaemia of a patient, and that gametocytes die at an age-dependent rate which increases under high asexual parasite densities. On average, 1 gametocyte per 156 asexual parasites (range 7.4-3700) is produced. The most remarkable findings are the large individual variation of conversion probabilities and circulation times, the average gametocyte circulation time of 6.4 days (range 1.3-22.2 days) which is more than twice the currently accepted value, and the large variation of conversion probabilities among successive waves of asexual parasitaemia without any particular time pattern. The latter finding could be explained by an association between conversion probability and variation of PfEMP1.
Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo
2001-09-01

Diverse death stimuli including anticancer drugs trigger apoptosis by inducing the translocation of cytochrome c from the outer mitochondrial compartment into the cytosol. Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. The results of this study show that on death induction by chemotherapeutic drugs, staurosporine and triggering of the death receptor CD95, cytochrome c not only translocates into the cytosol, but furthermore can be abundantly detected in the extracellular medium. The cytochrome c release from the cell is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. Interestingly, elevated cytochrome c levels were observed in sera from patients with hematologic malignancies. In the course of cancer chemotherapy, the serum levels of cytochrome c in the majority of the patients grew rapidly as a result of increased cell death. These data suggest that monitoring of cytochrome c in the serum of patients with tumors might serve as a useful clinical marker for the detection of the onset of apoptosis and cell turnover in vivo.
Evidence of a leading role for VEGF inBartonella henselae-induced endothelial cell proliferations
2001-09-01

Bartonella henselae causes the vasculoproliferative disorders bacillary angiomatosis (BA) and bacillary peliosis (BP). The pathomechanisms of these tumorous proliferations are unknown. Our results suggest a novel bacterial two-step pathogenicity strategy, in which the pathogen triggers growth factor production for subsequent proliferation of its own host cells. In fact, B. henselae induces host cell production of the angiogenic factor vascular endothelial growth factor (VEGF), leading to proliferation of endothelial cells. The presence of B. henselae pili was associated with host cell VEGF production, as a Pil- mutant of B. henselae was unable to induce VEGF production. In turn, VEGF-stimulated endothelial cells promoted the growth of B. henselae. Immunohistochemistry for VEGF in specimens from patients with BA or BP revealed increased VEGF expression in vivo. These findings suggest a novel bacteria-dependent mechanism of tumour growth.
Neuronal and Glial Coexpression of Argininosuccinate Synthetase and Inducible Nitric Oxide Synthase in Alzheimer Disease
2001-09-01

The enzyme argininosuccinate synthetase (ASS) is the rate limiting enzyme in the metabolic pathway leading from L-citrulline to L-arginine, the physiological substrate of all isoforms of nitric oxide synthases (NOS). ASS and inducible NOS (iNOS) expression in neurons and glia was investigated by immunohistochemistry in brains of Alzheimer disease (AD) patients and nondemented, age-matched controls. In 3 areas examined (hippocampus, frontal, and entorhinal cortex), a marked increase in neuronal ASS and iNOS expression was observed in AD brains. GFAP-positive astrocytes expressing ASS were not increased in AD brains versus controls, whereas the number of iNOS expressing GFAP-positive astrocytes was significantly higher in AD brains. Density measurements revealed that ASS expression levels were significantly higher in glial cells of AD brains. Colocalization of ASS and iNOS immunoreactivity was detectable in neurons and glia. Occasionally, both ASS-and iNOS expression was detectable in CD 68-positive activated microglia cells in close proximity to senile plaques. These results suggest that neurons and astrocytes express ASS in human brain constitutively, whereas neuronal and glial ASS expression increases parallel to iNOS expression in AD. Because an adequate supply of L-arginine is indispensable for prolonged NO generation, coinduction of ASS enables cells to sustain NO generation during AD by replenishing necessary supply of L-arginine.
Predictive Impact of 2-18Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography for Residual Postchemotherapy Masses in Patients With Bulky Seminoma
2001-09-01

PURPOSE: To establish the predictive potential of 2- 18 fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) for detecting viable tumor tissue in residual postchemotherapy masses of seminoma patients. PATIENTS AND METHODS: In this prospective multicenter trial, results of FDG PET studies in seminoma patients with postchemotherapy masses ≥ 1 cm were correlated with either the histology of the resected lesion or the clinical outcome on follow-up without resection. Negative PET scans of residual lesions that were devoid of viable tumor tissue on resection or disappeared, shrunk, or remained stable in size for at least 2 years were rated as true-negative (TN). Positive scans without histologic or clinical evidence of tumor tissue were classified as false-positive. In patients with histologically positive or progressive lesions, positive PET scans were defined as true-positive (TP) and negative scans, false-negative (FN). RESULTS: Thirty-seven PET scans of 33 patients were assessable at a median follow-up time of 23 months (range, 2 to 46 months). Histologic data were available from nine patients who had undergone resection. Twenty-eight patients were followed-up clinically and radiologically. Twenty-eight scans were TN, eight were TP, and one was FN. All 14 residual lesions more than 3 cm and 22 (96%) of the 23 ≤ 3 cm were correctly predicted by FDG PET. The specificity (100%; 95% confidence interval [CI], 87.7% to 100%), sensitivity (89%; 95% CI, 51.7% to 99.7%), positive predictive value (100%), and the negative predictive value (97%) of FDG PET were superior to data obtained by assessing residual tumor size (≤ or &gt; 3 cm). CONCLUSION: FDG PET is a clinically useful predictor of viable tumor in postchemotherapy residuals of pure seminoma, especially those greater than 3 cm.
Human Acid Ceramidase
2001-09-01

The biosynthesis of human acid ceramidase (hAC) starts with the expression of a single precursor polypeptide of approximately 53-55 kDa, which is subsequently processed to the mature, heterodimeric enzyme (40 + 13 kDa) in the endosomes/lysosomes. Secretion of hAC by either fibroblasts or acid ceramidase cDNA-transfected COS cells is extraordinarily low. Both lysosomal targeting and endocytosis critically depend on a functional mannose 6-phosphate receptor as judged by the following criteria: (i) hAC-precursor secretion by NH(4)Cl-treated fibroblasts and I-cell disease fibroblasts, (ii) inhibition of the formation of mature heterodimeric hAC in NH(4)Cl-treated fibroblasts or in I-cell disease fibroblasts, and (iii) blocked endocytosis of hAC precursor by mannose 6-phosphate receptor-deficient fibroblasts or the addition of mannose 6-phosphate. The influence of the six individual potential N-glycosylation sites of human acid ceramidase on targeting, processing, and catalytic activity was determined by site-directed mutagenesis. Five glycosylation sites (sites 1-5 from the N terminus) are used. The elimination of sites 2, 4, and 6 has no influence on lysosomal processing or enzymatic activity of recombinant ceramidase. The removal of sites 1, 3, and 5 inhibits the formation of the heterodimeric enzyme form. None of the mutant ceramidases gave rise to an increased rate of secretion, suggesting that lysosomal targeting does not depend on one single carbohydrate chain.
A High Performance Solver for the Animation of Deformable Objects using Advanced Numerical Methods
2001-09-01

Physically based modelling of deformable objects has become the most popular technique to model textiles, skin or human tissue. The crucial problem in the animation of deformable objects is the solution of the resulting differential equations. Recently fast solutions have been presented. In this work we will first give a theoretical analysis and then exploit special properties of the system and advanced numerical techniques to achieve further speed-ups of the simulations. Also, higher accuracy, leading to higher quality animations, will be achieved and an error bound is enforced.
Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL‐BFM 95 reinduction treatment
2001-09-01

Repeated asparaginase treatment has been associated with hypersensitivity reactions against the bacterial macromolecule in a considerable number of patients. Immunological reactions may range from anaphylaxis without impairment of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase activity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction treatment was performed prospectively in 76 children with newly diagnosed acute lymphoblastic leukaemia (ALL). According to the ALL‐Berlin–Frankfurt–Münster (BFM) 95 protocol, 10 000 U/m 2 body surface area of native Escherichia coli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 45/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginase activity were not available from the remaining 31 patients, but information with regard to hypersensitivity reactions only was given. Eighteen out of 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/l for at least 14 d was determined in 43 of the 45 patients who were analysed for enzyme activity.
Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique
2001-09-01

First-pass metabolism by the intestinal wall is extensive and contributes to the same extent as the liver to low bioavailability of some drugs such as verapamil. Moreover, intestinal secretion is as important as biliary excretion for the elimination of metabolites.
Using the jackknife-based scoring method for measuring LRP onset effects in factorial designs
2001-09-01

Miller, Patterson, and Ulrich (1998) introduced a jackknife-based method for measuring the differences between two conditions in the onset latencies of the lateralized readiness potential (LRP). The present paper generalizes such jackknife-based methods to factorial experiments with any combination of within- and between subjects factors. Specifically, we introduce a subsample scoring method to assess potential main and interaction effects on LRP onsets within conventional yet slightly adjusted analyses of variance (ANOVAs) and post hoc comparison procedures.
External Distraction of the Maxilla in Patients With Craniofacial Dysplasia
2001-09-01

Patients with severe maxillary hypoplasia secondary to craniofacial dysplasia present a challenge to the craniofacial surgeon. Maxillary distraction presents a promising tool to treat these patients more successfully. Fifteen patients aged 12 to 20 years with craniofacial dysplasia and maxillary retrusion were treated with two different techniques after complete Le Fort I osteotomy: one group underwent face mask protraction (2 patients), and the other group underwent rigid external distraction (13 patients). Cephalometric evaluation was performed before and after distraction. Rigid external distraction appeared to be superior to face mask protraction. Maxillary retrusion was fully corrected in this group. The path of maxillary positioning was well controlled by changing the traction force vector. Distraction osteogenesis has certainly improved treatment of these patients.
Comparative analysis of the association of HLA‐B*51 suballeles with Behçet’s disease in patients of German and Turkish origin
2001-09-01

Abstract: The distribution of the different HLA‐B*51 suballeles among patients with Behçet’s disease (BD) of German ( n =33) and Turkish ( n =92) origin in comparison to their presence in the respective ethnically matched healthy control groups (German: n =325, Turkish: n =93) was studied. HLA‐B*51x was significantly increased in both patient groups in comparison to the controls (Germans: 58% vs. 12%, OR 9.76, P &lt;0.001; Turkish: 75% vs. 25%, OR 9.13, P &lt;0.001). Molecular subtyping of B*51x revealed HLA‐B*51011 and B*5108 as the predominant suballeles in both patient groups and controls although with a slightly increased frequency of HLA‐B*5108 in the diseased individuals. HLA‐B*5105 was the only further HLA‐B*51x subtype detected in one Turkish patient heterozygous also for HLA‐B*5101. HLA‐B*5107 although present in a Turkish as well as German control was absent in the patient groups. There was also a tendency towards a higher degree of homozygosity for HLA‐B*51x in both patient groups versus the matched controls (Germans: 10% in patients vs. 2,5% in controls; Turkish: 27% in patients vs. 13% in controls). Our study further supports previous hypothesis of an association of BD with B51 suballeles which share amino‐acid residues at positions 63 and 67 as well as at positions 77–83 for specific peptide binding and natural killer (NK)‐cell interactions. This applies to HLA‐B*5101 and B*5108, but not to HLA‐B*5107 different at position 67, which could be negatively associated with BD.
Determination of the enantiomerization barrier of thalidomide by dynamic capillary electrokinetic chromatography
2001-09-01

Enantioselective chromatographic methods, representing the most commonly used techniques for the determination of enantiomeric ratios, can also be used for the evaluation of stereochemical integrity. In the present study, dynamic capillary electrokinetic chromatography (DEKC) was employed to determine the enantiomerization barrier of thalidomide. In the presence of the chiral mobile phase additive carboxymethyl-beta-cyclodextrin, the interconverting enantiomers of thalidomide produced characteristic elution profiles exhibiting plateaus and/or peak broadening between 25 and 55 degrees C at pH 8. To obtain the enantiomerization barrier of thalidomide from experimental data, the fast and efficient simulation program ChromWin was used to simulate the experimental interconversion profiles and to obtain the apparent rate constants k1app(T). Additionally, these values were compared with the novel approximation function for the direct calculation of enantiomerization barriers from chromatographic parameters of elution profiles. From the rate constants k1app(T) of temperature-dependent measurements the kinetic activation parameters deltaG(T)#,deltaH#, and deltaS# of the enantiomerization of thalidomide were obtained. At 25 degrees C, the enantiomerization barrier deltaG# was determined to be 102 +/- 1 kJ/mol at pH 8 in the dynamic electrokinetic chromatographic experiment.
Characterization of the Single Superoxide Dismutase of Staphylococcus xylosus
2001-09-01

ABSTRACT Staphylococcus xylosus is a facultative anaerobic bacterium used as a starter culture for fermented meat products. In an attempt to analyze the antioxidant capacities of this organism, the superoxide dismutase (SOD) was characterized. S. xylosus contains a single cytoplasmic SOD, which was not inhibited by H 2 O 2 . The SOD activity in crude extracts was completely lost upon metal depletion, but it could be recovered by manganese and very weakly by iron. It is therefore suggested that the S. xylosus SOD is a manganese-preferring enzyme. The corresponding gene, sod , was isolated from a genomic library of S. xylosus DNA and complemented the growth defect of an Escherichia coli SOD-deficient mutant. As deduced from the nucleotide sequence, sod encodes a protein of 199 amino acids with a molecular mass of 22.5 kDa. Two transcriptional start sites 25 and 120 bp upstream of the sod start codon were identified. A terminator-like structure downstream of the gene suggested a monocistronic sod mRNA. Regulation of sod expression was studied using fusions of the sod promoters to a genomic promoterless β-galactosidase gene. The sod expression was not affected by manganese and increased slightly with paraquat. It was induced during stationary phase in a complex medium but not in a chemically defined medium. To investigate the physiological role of SOD, a mutant devoid of SOD activity was constructed. Growth experiments showed that sod is not essential for aerobic growth in complex medium. However, in chemically defined medium without leucine, isoleucine, and valine, the sod mutant hardly grew, in contrast to the wild-type strain. In addition, the mutant was sensitive to hyperbaric oxygen and to paraquat. Therefore, sod plays an important role in the protection of S. xylosus from oxidative stress.
Simocyclinones: diversity of metabolites is dependent on fermentation conditions 3
2001-09-01

Simocyclinones, a novel group of angucyclinone antibiotics, are produced by Streptomyces antibioticus Tü 6040. The compounds show antibacterial and antitumor properties. In submerged cultivation, the production of simocyclinones is strongly dependent on the carbon and nitrogen sources used in a chemically defined medium. Productivity of distinct components and diversity of simocyclinone compounds are influenced by the medium composition. Four series of simocyclinone compounds were detected by high-performance liquid chromatography (HPLC) diode array detector (DAD) and HPLC electrospray ionization (ESI) mass spectrometry (MS) analysis, isolated and the structures determined by nuclear magnetic resonance (NMR) techniques. Under optimized conditions, simocyclinone D8 was produced in an amount of 300 mg l(-1) and simocyclinone C4 in a concentration up to 50 mg l(-1).
Functional Significance of the UCSNP-43 Polymorphism in the CAPN10 Gene for Proinsulin Processing and Insulin Secretion in Nondiabetic Germans
2001-09-01

Recently, an association of the G allele in UCSNP-43 of calpain 10 with type 2 diabetes and decreased glucose disposal was reported. Calpain 10 is also expressed in pancreatic islets. It is not known, however, whether and how this polymorphism contributes to the biological variation of β-cell function. We studied 73 nondiabetic subjects from the southwest region of Germany (G/G, n = 41; G/A, n = 29; and A/A, n = 3) using a modified hyperglycemic clamp (10 mmol/l glucose, added glucagon-like peptide 1, final arginine bolus). The genotype distribution was not different between subjects with normal glucose tolerance (n = 56) and those with impaired glucose tolerance (n = 17; P = 0.74, χ2 test). First-phase insulin secretion (adjusted for sex and insulin sensitivity from hyperglycemic clamp) was greater in G/G (2,747 ± 297 pmol/min) than in G/A + A/A (1,612 ± 156 pmol/min, P = 0.003). Insulin secretion in response to arginine (adjusted for insulin sensitivity) was also greater in G/G (9,648 ± 1,186 pmol/min) than in G/A + A/A (5,686 ± 720 pmol/min, P = 0.04). The acute poststimulus proinsulin-to-insulin ratio was lower in G/G (1.6 ± 0.4% first phase; 1.6 ± 0.2% arginine) than in G/A + A/A (4.0 ± 0.5% first phase, P &amp;lt; 0.001; 2.5 ± 0.4% arginine, P = 0.03). In conclusion, it appears unlikely that any association of the UCSNP-43 polymorphism alone with type 2 diabetes involves impairment of insulin secretion in our population of German Caucasians. This may be entirely different with specific haplotype combinations.
Endocrine and Paracrine Regulation of Endometrial Angiogenesis
2001-09-01

Abstract The human endometrium is a complex tissue comprised of different cell types, including epithelial, stromal, inflammatory, perivascular, and blood vessel cells. The hormonal receptivity and distribution of these cell populations change during the menstrual cycle. Cyclical endometrial growth is dependent on its ability to regenerate a vascular capillary network, which grows in parallel with the proliferation and differentiation of the endometrial lining. Natural hormonal effects on the endometrium and endocrine manipulation of this tissue, in response to the use of exogenous steroid therapies, can affect endometrial capillary proliferation and function, leading to clinical abnormalities of uterine bleeding. We propose that the regulation of endometrial angiogenesis is mediated indirectly via complex interactions among cell types. Our laboratory has focused on a prototypical member of the angiogenic proteins, vascular endothelial growth factor (VEGF)‐A. In this paper we present data demonstrating that VEGF‐A expression in normal endometrial epithelial and stromal cells and in Ishikawa adenocarcinoma cells is increased by an ovarian steroid, estradiol. Infiltrating immune cells, particularly polymorphonuclear granulocytes, also are sources of VEGF‐A. In inflammatory conditions involving the endometrium (e.g., endometriosis), a proinflammatory cytokine, IL‐1β, can mediate neoangiogenesis by inducing VEGF‐A gene transcription. Thus, endometrial vascularization is effected by both endocrine and paracrine pathways.
Spontaneous occlusion of a cerebral arteriovenous malformation: angiography and MR imaging follow-up and review of the literature.
2001-09-01

We present the angiographic and MR imaging course of a 62-year-old man with a right parietal high-flow arteriovenous malformation (AVM), which was diagnosed because of seizures. A spontaneous, complete, and asymptomatic occlusion of the AVM was confirmed by a second angiography 3 months later. The possible mechanisms leading to the occlusion are discussed, and a brief review of the literature is given.