julilili42/papers huggingface dataset:
T Cell Epitopes of Human Myelin Oligodendrocyte Glycoprotein Identified in HLA-DR4 (DRB1*0401) Transgenic Mice Are Encephalitogenic and Are Presented by Human B Cells
2001-12-15

Abstract Myelin oligodendrocyte glycoprotein (MOG) is an Ag present in the myelin sheath of the CNS thought to be targeted by the autoimmune T cell response in multiple sclerosis (MS). In this study, we have for the first time characterized the T cell epitopes of human MOG restricted by HLA-DR4 (DRB1*0401), an MHC class II allele associated with MS in a subpopulation of patients. Using MHC binding algorithms, we have predicted MOG peptide binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T cell reactivity to overlapping MOG peptides by testing HLA-DR4 (DRB1*0401) transgenic mice immunized with recombinant human (rh)MOG. The data indicated that MOG peptide 97–108 (core 99–107, FFRDHSYQE) was the immunodominant HLA-DR4-restricted T cell epitope in vivo. This peptide has a high in vitro binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced severe experimental autoimmune encephalomyelitis in the HLA-DR4 transgenic mice. Interestingly, the same peptide was presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG epitopes in the pathogenesis of human MS.
Subcellular distribution of 14‐3‐3 proteins in the unicellular green alga Chlamydomonas reinhardtii
2001-12-15

A polyclonal antibody was raised against a recombinant Chlamydomonas 14‐3‐3–β‐galactosidase (β‐Gal) fusion protein and characterized for its epitope specificity towards the corresponding Chlamydomonas 14‐3‐3 protein by scan‐peptide analysis. This antibody recognized four Chlamydomonas polypeptides with apparent molecular masses 32, 30, 27, and 24 kDa, which also reacted with the antiserum depleted of anti‐( Escherichia coli β‐Gal) IgG, but not with the corresponding preimmune serum or the antiserum preincubated with purified 14‐3‐3 proteins. Western‐blot analyses performed with the antibody depleted of anti‐(β‐Gal) IgG revealed that more or less pronounced levels of 14‐3‐3 proteins were present in all subcellular fractions of Chlamydomonas reinhardtii except the nuclei. The highest levels of 14‐3‐3 protein were observed in the cytosol and microsomal fraction. The 30‐kDa isoform was predominant in the cytosol, whereas the 27‐kDa isoform was prevalent in the microsomes. When microsomal membranes were separated by sucrose‐density‐gradient centrifugation, Western‐blot analysis revealed distinct patterns of 14‐3‐3 isoforms in the endoplasmic reticulum, dictyosome, and plasma membrane fractions identified by marker enzyme activities. These findings indicate that the four 14‐3‐3 proteins of C. reinhardtii differentially interact with endoplasmic reticulum, dictyosomes, and plasma membrane.
The Biosynthesis of Vancomycin-Type Glycopeptide Antibiotics-The Order of the Cyclization Steps
2001-12-17

Linear and bicyclic glycopeptides occur as intermediates in the biosynthesis of the aglycon of glycopeptide antibiotics of the type shown. Considering the structures of these peptides and those of previously isolated analogues, the sequence of the three oxidative ring-closing steps can be deduced for type-I and type-II glycopeptide antibiotics. Thus, comprehensive insight into the assembly of the aglycon is achieved for the first time.
Determination of the enantiomerization barrier of chlorthalidone by dynamic electrokinetic chromatography and computer simulation.
2001-12-17

Dynamic electrokinetic chromatography (DEKC) and computer simulation have been used to determine the enantiomerization barrier of the drug chlorthalidone, which is commonly employed as a diuretic. The separation of enantiomers was performed in an aqueous 100 mM citric acid/phosphate buffer system at pH 5 containing 12.5 mg/mL carboxymethyl-beta-cyclodextrin and dimethyl-beta-cyclodextrin each as a dual chiral recognition system. The enantiomerization that occurred during separation resulted in a peak distortion, i.e., plateau formation and peak broadening. The interconversion profiles were simulated with ChromWin software, which is based on the theoretical plate as well as on the stochastic model using the experimental data plateau height, hplateau; peak width at half height, Wh, and total retention time, tR. Peak form analysis yielded the rate constants, k1 and k(-1) as well as the kinetic activation parameters, deltaG++, deltaH++, and deltaS++ of the enantiomerization reaction of chlorthalidone 1. At 37.5 degrees C, the enantiomerization barrier, deltaG++, was determined to be 100.6 +/- 0.4 kJ/mol(-1); the activation parameters by temperature-dependent measurement, deltaH++ = 69.2 +/- 0.2 kJ/mol , deltaS++ = -101 +/- 6 J K(-1) mol(-1) and the half-life, tau, was found to be approximately 2.5 hr.
ChemInform Abstract: An Expeditious Synthesis of Optically Pure 1,4,5,6‐Tetrahydro‐as‐triazines, Fused to the Carbohydrate Skeleton.
2001-12-18

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Application of the E‐screen assay to test for oestrogenically active substances in swine feed
2001-12-20

A pig breeder in central Hesse (Germany) noticed the occurrence of enlarged vulvae in female piglets. Intoxication with oestrogenically active substances by contamination of two feed mixes ingested by the mother sows appeared to be a possible cause. Using a combined technique of the DFG analytical method S19 and the E‐screen assay, two feed samples were found to contain powerful oestrogenically active compounds. By co‐incubation with the anti‐oestrogen tamoxifen it could be clearly demonstrated that the oestrogenic activity was mediated by the oestrogen receptor. These results demonstrate that use of the E‐screen assay in combination with the DFG analytical method S19 provides a simple and readily useable prescreening method for the routine detection of oestrogenically active compounds in animal feed. The results from the E‐screen assay show that the sows ingested 10–80 μg oestradiol equivalents per day in their feed. Because of the bioavailability of these substances, the oestrogenic active compounds seem to be transferred into the milk and passed to the piglets via suckling. The milk of the dam appears to contain this substance in biologically active form and at such high concentrations that the female piglets had enlarged vulvae.
Stability of Na–Be minerals in late-magmatic fluids of the Ilímaussaq alkaline complex, South Greenland
2001-12-21

Various Na-bearing Be silicates occur in late-stage veins and in alkaline rocks metasomatised by late-magmatic fluids of the Ilímaussaq alkaline complex in South Greenland. First, chkalovite crystallised with sodalite around 600°C at 1 kbar. Late-magmatic assemblages formed between 400 and 200°C and replaced chkalovite or grew in later veins from an H2O-rich fluid. This fluid is also recorded in secondary fluid inclusions in most Ilímaussaq nepheline syenites. The late assemblages comprise chkalovite + ussingite, tugtupite + analcime ± albite, epididymite + albite, bertrandite ± beryllite + analcime, and sphaerobertrandite + albite or analcime(?). Quantitative phase diagrams involving minerals of the Na–Al–Si–O–H–Cl system and various Be minerals show that tugtupite co-exists at 400°C only with very Na-rich or very alkalic fluids [log (aNa+/aH+) &gt; 6–8; log (aBe2+/(aH+)2) &gt; –3]. The abundance of Na-rich minerals and of the NaOH-bearing silicate ussingite indicates the importance of both of these parameters. Water activity and silica activity in these fluids were in the range 0.7–1 and 0.05–0.3, and XNaCl in a binary hydrous fluid was below 0.2 at 400°C. As bertrandite is only stable at &lt; 220°C at 1 kbar, the rare formation of epididymite, eudidymite, bertrandite and sphaerobertrandite by chkalovite-consuming reactions occurred at still lower temperatures and possibly involved fluids of higher silica activity.
Quantitative determination of phospholipids in a pharmaceutical drug by scanning and video densitometry.
2001-12-21

This paper describes a convenient and practice method for quantitation of surfactant phospholipids (1,2-dipalmitoyl-3-sn-phosphatidyl choline [DPPC] and 1-palmitayl-2-oleyl-3-sn-phosphatidyl glycerol [POPG]) in a recombinant surfactant lyophile (Venticute) by high-performance, thin-layer chromatography (HPTLC) with video densitometry. DPPC and POPG were extracted from Venticute-lyophile using methanol. Separation from the other active ingredients and excipients was accomplished by HPTLC on silica gel F254 plates with a mixture of chloroform, methanol, glacial acetic acid, and water as development solvent. Postchromatographic derivatization by dipping in copper sulphate/phosphoric acid reagent and subsequent heating shows grey-brown bands on a light blue background. These were detected with the video densitometer in the VIS range, and with scanning densitometry at 365 nm. Linear calibration in a working range of 0.7-1.3 microg DPPC and 0.35-0.65 microg POPG was demonstrated by integrating the area under the peaks. Good results were obtained with recovery experiments. When compared to classical slit scanning densitometry, video densitometry represents a fast alternative to quantitate thin-layer chromatograms in surfactant phospholipid analysis.
ChemInform Abstract: Resins and Anchors for Solid Phase Organic Synthesis
2001-12-25

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Disruption of the taurine transporter gene ( taut ) leads to retinal degeneration in mice
2001-12-28

ABSTRACT Taurine is involved in cell volume homeostasis, antioxidant defense, protein stabilization, and stress responses. High levels of intracellular taurine are maintained by a Na + ‐dependent taurine transporter (TAUT) in the plasma membrane. In view of the immunomodulatory and cytoprotective effects of taurine, a mouse model with a disrupted gene coding for the taurine transporter (taut‐/‐ mice) was generated. These mice show markedly decreased taurine levels in a variety of tissues, a reduced fertility, and loss of vision due to severe retinal degeneration. In particular, the retinal involvement identifies the taurine transporter as an important factor for the development and maintenance of normal retinal functions and morphology.
Preradiation chemotherapy for pediatric patients with high‐grade glioma
2001-12-28

Abstract BACKGROUND To evaluate the feasibility and efficacy of intensive chemotherapy given prior to irradiation in pediatric patients with malignant glioma, the Society of Pediatric Oncology in Germany started a randomized trial in 1991. The high‐grade glioma strata had to be closed because of insufficient patient accrual. The follow‐up data from these patients are reported. METHODS Fifty‐two patients with World Health Organization (WHO) Grade 4 malignant glioma ( n = 27 patients) or with WHO Grade 3 anaplastic astrocytoma ( n = 25 patients) between the ages of 3 years and 17 years were available for analysis. The tumor locations were supratentorial in 42 patients, the cerebellum in 8 patients, and the spinal cord in 2 patients (the brainstem was excluded). Tumor surgeries were biopsy in 10 patients, partial resection in 5 patients, subtotal resection in 10 patients, and macroscopic total resection in 21 patients. Patients received either 54 grays of irradiation ( n = 22 patients) followed by chemotherapy with lomustine, vincristine, and cisplatin ( maintenance chemotherapy) or sandwich chemotherapy ( n = 30 patients), which consisted of ifosfamide, etoposide, methotrexate, cisplatin, and cytosine arabinoside followed by irradiation. RESULTS The extent of resection was the most important prognostic factor. The median survival was 5.2 years for patients who underwent tumor resection of ≥ 90% compared with 1.3 years for patients who underwent less than complete resection ( P &lt; 0.0005). After undergoing macroscopic total resection, sandwich chemotherapy ( n = 15 patients) resulted in better overall survival (median, 5.2 years) compared with the maintenance protocol ( n = 16 patients; median survival, 1.9 years; P = 0.015). A Cox multivariate regression analysis showed better survival for female patients ( P = 0.025), WHO Grade 3 disease ( P = 0.016), tumor resection of ≥ 90% ( P = 0.003), irradiation with ≥ 54 grays ( P = 0.003), and sandwich chemotherapy ( P = 0.006). CONCLUSIONS These data suggest that early, intensive chemotherapy increases survival rates in patients with malignant glioma who undergo complete resection. Cancer 2002;94:264–71. © 2002 American Cancer Society.
Insulin analogues: impact of cell model characteristics on results and conclusions regarding mitogenic properties
2001-12-31

In a publication in the June issue of the journal Diabetes, [Kurtzhals et al. (2000)] reported on experiments with different insulin analogues. The authors compared the four insulin analogues lispro, aspartat, detemir and glargine using a series of in-vitro parameters which they believed to be related to efficacy and safety. One of their findings was an increased IGF-1 receptor affinity and mitogenic potency in a human osteosarcoma cell line of glargine compared to human insulin. Although the authors inferred that these findings could have implications for the in-vivo safety of glargine, this point was not directly assessed in their study, and they concluded that the safety implications of their findings are unclear.
Further evidence for direct vascular actions of statins: Effect on endothelial nitric oxide synthase and adhesion molecules
2001-12-31

The effect of the synthetic statin fluvastatin was investigated on the concentrations of endothelial nitric oxide synthase (eNOS) and of soluble adhesion molecules in human vascular endothelial cell cultures. Fluvastatin was able to increase dose-dependently eNOS concentration. In addition, fluvastatin reduced concentrations of E-Selectin and ICAM-1. These results further support the evidence that statins elicit important effects on the vascular endothelium which may contribute to the reduction of morbidity and mortality of cardiovascular diseases.
Macroencapsulation of rat islets without alteration of insulin secretion kinetics
2001-12-31

Transplantation of encapsulated islets may restore endogenous insulin secretion in type 1 diabetics with no need of lifetime immunosuppression of the recipient. A biomaterial should be developed which combined immunoisolation with rapid and efficient diffusion of glucose and insulin. Rat islets were macroencapsulated in capillaries (molecular cut off 50 kD) of differently modified polysulphone. Macroencapsulated islets were perifused to study the kinetics of glucose induced insulin secretion into the perifusion medium. Blending polysulphone (PSU) with poly vinyl pyrrolidone or sodium dodecyl sulphate was not suited for islet macroencapsulation since glucose induced insulin release was absent after encapsulation. Hydroxy methylation (CH2OH) of PSU improved the secretory behaviour of macroencapsulated islets depending on the degree of substitution (DS). At 0.8 DS glucose induced insulin secretion was delayed and inefficient. At maximal degrees of PSU-substitution (1.8) the kinetics of insulin release and the efficiency of insulin release were very similar to that observed of free floating islets. In conclusion, highly substituted hydroxy methylated polysulphone allows a rapid and efficient insulin release after macroencapsulation and is suited for the further development of a bioartificial pancreas.
Finite elements in computational electromagnetism
2002-01-01

This article discusses finite element Galerkin schemes for a number of linear model problems in electromagnetism. The finite element schemes are introduced as discrete differential forms, matching the coordinate-independent statement of Maxwell's equations in the calculus of differential forms. The asymptotic convergence of discrete solutions is investigated theoretically. As discrete differential forms represent a genuine generalization of conventional Lagrangian finite elements, the analysis is based upon a judicious adaptation of established techniques in the theory of finite elements. Risks and difficulties haunting finite element schemes that do not fit the framework of discrete differential forms are highlighted.
AAA-ATPase p97/Cdc48p, a Cytosolic Chaperone Required for Endoplasmic Reticulum-Associated Protein Degradation
2002-01-01

Endoplasmic reticulum-associated degradation (ERAD) disposes of aberrant proteins in the secretory pathway. Protein substrates of ERAD are dislocated via the Sec61p translocon from the endoplasmic reticulum to the cytosol, where they are ubiquitinated and degraded by the proteasome. Since the Sec61p channel is also responsible for import of nascent proteins, this bidirectional passage should be coordinated, probably by molecular chaperones. Here we implicate the cytosolic chaperone AAA-ATPase p97/Cdc48p in ERAD. We show the association of mammalian p97 and its yeast homologue Cdc48p in complexes with two respective ERAD substrates, secretory immunoglobulin M in B lymphocytes and 6myc-Hmg2p in yeast. The membrane 6myc-Hmg2p as well as soluble lumenal CPY*, two short-lived ERAD substrates, are markedly stabilized in conditional cdc48 yeast mutants. The involvement of Cdc48p in dislocation is underscored by the accumulation of ERAD substrates in the endoplasmic reticulum when Cdc48p fails to function, as monitored by activation of the unfolded protein response. We propose that the role of p97/Cdc48p in ERAD, provided by its potential unfoldase activity and multiubiquitin binding capacity, is to act at the cytosolic face of the endoplasmic reticulum and to chaperone dislocation of ERAD substrates and present them to the proteasome.
Control over location-based response activation in the Simon task: Behavioral and electrophysiological evidence.
2002-01-01

In 4 Simon experiments the authors examined control over 2 routes of sensorimotor processing: response priming in the unconditional route and response selection via the conditional route. The Simon effect diminished as the frequency of noncorresponding trials increased. Location-based response priming was observed only when the stimulus followed a corresponding event but not after a noncorresponding trial. Therefore, the unconditional route appears to be suppressed whenever the task context indicates priming as potentially disadvantageous. Moreover, the task-irrelevant stimulus location was used for response selection as a function of correspondence probability. Although exact repetitions of stimulus-response sequences caused a marked speed-up of responses, this 3rd mechanism is independent of unconditional route suppression and frequency-based adjustments in the conditional route.
Association of the T-G Polymorphism in Adiponectin (Exon 2) With Obesity and Insulin Sensitivity
2002-01-01

The adipocyte-derived hormone adiponectin seems to protect from insulin resistance, a key factor in the pathogenesis of type 2 diabetes. Genome-wide scans have mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. A common silent T-G exchange in nucleotide 94 (exon 2) of the adiponectin gene has been associated with increased circulating adiponectin levels. Metabolic abnormalities associated with the G allele have not been reported. We therefore assessed whether this polymorphism alters insulin sensitivity and/or measures of obesity using the Tübingen Family Study database (prevalence of the G allele, 28%). In 371 nondiabetic individuals, we found a significantly greater BMI in GG + GT (25.5 ± 0.7 kg/m2) compared with TT (24.1 ± 0.3 kg/m2; P = 0.02). Insulin sensitivity (determined by euglycemic clamp, n = 209) was significantly lower in GG + GT (0.089 ± 0.007 units) compared with TT (0.112 ± 0.005 units; P = 0.02). This difference disappeared completely on adjustment for BMI. Because our population contains a relatively high proportion of first-degree relatives of patients with type 2 diabetes, we stratified by family history (FHD). Much to our surprise, the genotype differences in BMI and insulin sensitivity in the whole population were attributable entirely to differences in the subgroup without FHD, whereas in the subgroup with FHD, the G allele had absolutely no effect. Moreover, individuals without FHD had a significantly lower BMI than individuals with FHD (25.2 ± 0.4 vs. 26.2 ± 0.5 kg/m2; P = 0.01), which was not the case for the GG + GT subgroup without FHD (27.0 ± 0.9 kg/m2; NS). This suggests that in individuals without familial predisposition for type 2 diabetes, the adiponectin polymorphism may mildly increase the obesity risk (and secondarily insulin resistance). In contrast, in individuals who are already burdened by other genetic factors, this small effect may be very hard to detect.
T cells and aging january 2002 update
2002-01-01

Age-related changes in the immune system may contribute to morbidity and mortality due to decreased resistance to infection and, possibly, certain cancers in the aged. Many studies mostly performed in mice, rats and man but also including monkeys and dogs have established that age-associated immune decline is characterized by decreases in both humoral and cellular responses. The former may be largely a result of the latter, because observed changes both in the B cell germline-encoded repertoire and the age-associated decrease in somatic hypermutation of the B cell antigen receptors are now known to be critically affected by helper T cell aging. As antigen presenting cell (APC) function appears to be well-maintained in the elderly, this review will focus on the T cell. Factors contributing to T cell immunosenescence may include a) altered production of T cell progenitors (stem cell defects, stromal cell defects), b) decreased levels of newly-generated mature T cells (thymic involution), c) aging of resting immune cells, d) disrupted activation pathways in immune cells (stimulation via the T cell receptor for antigen, costimulation, apoptosis control), e) replicative senescence of clonally expanding cells. This review aims to consider the current state of knowledge on the scientific basis for and potential clinical relevance of those factors in immunosenescence in humans. Experiments in other species will be touched upon with the proviso that there are clearly differences between them, especially between humans and rodents, but exactly what those differences are is not completely clear. Given its potential importance and the increasing proportion of elderly people the world over, coupled with the realisation that whereas mortality is decreasing, morbidity may not be decreasing in parallel (1), a better understanding of the causes and impact of immunosenescence may offer the possibility of identifying where prevention or delay of onset, as well as therapeutic intervention, might be beneficial. Amelioration of the effects of dysregulated immune responses in the elderly by replacement therapy, supplementation therapy or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age.