julilili42/papers huggingface dataset:
Protein–Protein Interactions between Sucrose Transporters of Different Affinities Colocalized in the Same Enucleate Sieve Element
2002-07-01

Suc represents the major transport form for carbohydrates in plants. Suc is loaded actively against a concentration gradient into sieve elements, which constitute the conduit for assimilate export out of leaves. Three members of the Suc transporter family with different properties were identified: SUT1, a high-affinity Suc proton cotransporter; SUT4, a low-affinity transporter; and SUT2, which in yeast is only weakly active and shows features similar to those of the yeast sugar sensors RGT2 and SNF3. Immunolocalization demonstrated that all three SUT proteins are localized in the same enucleate sieve element. Thus, the potential of Suc transporters to form homooligomers was tested by the yeast-based split-ubiquitin system. The results show that both SUT1 and SUT2 have the potential to form homooligomers. Moreover, all three Suc transporters have the potential to interact with each other. As controls, a potassium channel and a monosaccharide transporter, expressed in the plasma membrane, did not interact with the SUTs. The in vivo interaction between the functionally different Suc transporters indicates that the membrane proteins are capable of forming oligomeric structures that, like mammalian Glc transporter complexes, might be of functional significance for the regulation of transport.
Bilateral lesions of thalamus and basal ganglia: origin and outcome
2002-07-01

Twenty-seven MRI examinations from 17 children (7 females, 10 males) with bilateral lesions of the basal ganglia and thalamus, presenting over a period of 8 years, were reevaluated, and correlated with the type of cerebral palsy (CP) as well as motor and cognitive impairment. Children were between 1 year 6 months and 17 years old at last examination (mean 5 years 9 months). Brain damage had occurred as a consequence of birth asphyxia in nine patients and of neonatal shock in four patients. No adverse event could be identified in four children. In these, late prenatal compromise is assumed, as extensive screening (including MR spectroscopy in two patients) did not yield an underlying metabolic disorder. Three different degrees of MRI lesion patterns could be defined: a mild pattern (involvement of nucleus lentiformis and ventro-lateral thalamus only; n=7), an intermediate pattern (involvement of nucleus lentiformis, ventro-lateral thalamus, and pericentral region; n=3), and a severe pattern (involvement of nucleus lentiformis, entire thalamus, pericentral region, and hippocampus; n=7). This grading of MRI findings correlated significantly with the severity of both cognitive and motor impairment and type of CP. Normal cognitive development and mild motor delay was only seen with the mild pattern. All children developed CP: purely dyskinetic CP was only seen with the mild pattern, whereas the dyskinetic-spastic or spastic CP types could be seen in all three lesion patterns, with dyskinetic-spastic CP more related to the moderate, and purely spastic CP more related to the severe pattern.
Interactions between sterol biosynthesis genes in embryonic development of Arabidopsis
2002-07-01

Summary The sterol biosynthesis pathway of Arabidopsis produces a large set of structurally related phytosterols including sitosterol and campesterol, the latter being the precursor of the brassinosteroids (BRs). While BRs are implicated as phytohormones in post‐embryonic growth, the functions of other types of steroid molecules are not clear. Characterization of the fackel ( fk ) mutants provided the first hint that sterols play a role in plant embryogenesis. FK encodes a sterol C‐14 reductase that acts upstream of all known enzymatic steps corresponding to BR biosynthesis mutants. Here we report that genetic screens for fk ‐like seedling and embryonic phenotypes have identified two additional genes coding for sterol biosynthesis enzymes: CEPHALOPOD (CPH), a C‐24 sterol methyl transferase, and HYDRA1 (HYD1), a sterol C‐8,7 isomerase. We describe genetic interactions between cph , hyd1 and fk , and studies with 15‐azasterol, an inhibitor of sterol C‐14 reductase. Our experiments reveal that FK and HYD1 act sequentially, whereas CPH acts independently of these genes to produce essential sterols. Similar experiments indicate that the BR biosynthesis gene DWF1 acts independently of FK , whereas BR receptor gene BRI1 acts downstream of FK to promote post‐embryonic growth. We found embryonic patterning defects in cph mutants and describe a GC–MS analysis of cph tissues which suggests that steroid molecules in addition to BRs play critical roles during plant embryogenesis. Taken together, our results imply that the sterol biosynthesis pathway is not a simple linear pathway but a complex network of enzymes that produce essential steroid molecules for plant growth and development.
Bilateral lesions of thalamus and basal ganglia: origin and outcome
2002-07-01

Twenty‐seven MRI examinations from 17 children (7 females, 10 males) with bilateral lesions of the basal ganglia and thalamus, presenting over a period of 8 years, were reevaluated, and correlated with the type of cerebral palsy (CP) as well as motor and cognitive impairment. Children were between 1 year 6 months and 17 years old at last examination (mean 5 years 9 months). Brain damage had occurred as a consequence of birth asphyxia in nine patients and of neonatal shock in four patients. No adverse event could be identified in four children. In these, late prenatal compromise is assumed, as extensive screening (including MR spectroscopy in two patients) did not yield an underlying metabolic disorder. Three different degrees of MRI lesion patterns could be defined: a mild pattern (involvement of nucleus lentiformis and ventro‐lateral thalamus only; n=7), an intermediate pattern (involvement of nucleus lentiformis, ventro‐lateral thalamus, and pericentral region; n=3), and a severe pattern (involvement of nucleus lentiformis, entire thalamus, pericentral region, and hippocampus; n=7). This grading of MRI findings correlated significantly with the severity of both cognitive and motor impairment and type of CP. Normal cognitive development and mild motor delay was only seen with the mild pattern. All children developed CP: purely dyskinetic CP was only seen with the mild pattern, whereas the dyskinetic‐spastic or spastic CP types could be seen in all three lesion patterns, with dyskinetic‐spastic CP more related to the moderate, and purely spastic CP more related to the severe pattern.
Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil
2002-07-01

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. Some case reports and pilot studies have suggested efficacy against systemic lupus erythematosus (LE), particularly in the case of lupus nephritis. Reports on MMF treatment of skin manifestations of LE are still anecdotal. We report two cases with extensive skin lesions owing to subacute cutaneous LE (SCLE). Both patients had been treated with azathioprine and antimalarials without effect. Finally both patients were given highly dosed glucocorticosteroids, which were also ineffective but led to vertebral fractures because of long-term steroid treatment in one patient and steroid-induced psychosis in the other. MMF 2 g daily caused the skin manifestations to disappear within a few weeks in both patients. One patient was followed up for more than 24 months, and showed good toleration of MMF treatment. The skin remained stable over this period when at least 1 g MMF per day was administered. In conclusion, MMF appears to be an attractive treatment option in skin manifestations of SCLE, and seems to be beneficial for patients with steroid-refractory lesions that are also resistant to treatment with immunosuppressants or antimalarials. The observations suggest that further evaluation of this route in randomized controlled trials is warranted.
Study of the role of leukotriene B4 in abnormal function of human subchondral osteoarthritis osteoblasts: Effects of cyclooxygenase and/or 5‐lipoxygenase inhibition
2002-07-01

Abstract Objective To compare the effect of licofelone, NS‐398 (an inhibitor of cyclooxygenase 2 [COX‐2]), and BayX‐1005 (an inhibitor of 5‐lipoxygenase activating protein) on the production of leukotriene B 4 (LTB 4 ) and prostaglandin E 2 (PGE 2 ), and on cell biomarkers by human osteoarthritis (OA) subchondral osteoblasts. Methods Primary in vitro osteoblasts were prepared from subchondral bone specimens obtained from OA patients and autopsy subjects. LTB 4 and PGE 2 levels were measured by enzyme‐linked immunosorbent assay in conditioned media of osteoblasts incubated in the presence or absence of licofelone, NS‐398, or BayX‐1005. The effect of these drugs or of the addition of LTB 4 on alkaline phosphatase (AP) activity and osteocalcin release by OA and normal osteoblasts was determined. The presence of LTB 4 receptors in normal and OA osteoblasts was evaluated by Western blot analysis. Results OA osteoblasts produced variable levels of PGE 2 and LTB 4 compared with normal osteoblasts. Licofelone, at the maximal dose used, inhibited production of PGE 2 and LTB 4 by OA osteoblasts by a mean ± SEM of 61.2 ± 6.4% and 67.0 ± 7.6%, respectively. NS‐398 reduced PGE 2 production by 75.8 ± 5.3%. BayX‐1005 inhibited LTB 4 production in OA osteoblasts by 38.7 ± 14.5% and marginally affected PGE 2 levels (reduction of 14.8 ± 5.3%). Licofelone dose‐dependently stimulated 1,25‐dihydroxyvitamin D‐induced AP activity while inhibiting osteocalcin release. BayX‐1005 partly reproduced these effects, but NS‐398 failed to affect them. LTB 4 dose‐dependently inhibited AP activity in OA osteoblasts, while its effect on osteocalcin depended on endogenous LTB 4 levels in these cells. In normal osteoblasts, LTB 4 dose‐dependently stimulated osteocalcin, whereas it failed to influence AP. LTB 4 receptors BLT1 and BLT2 were present in normal and OA osteoblasts. Conclusion Licofelone inhibits the production of PGE 2 and LTB 4 . Selective effects of licofelone on AP and osteocalcin occur via its role on LTB 4 production. Because LTB 4 can modify cell biomarkers in OA and normal osteoblasts, our results suggest licofelone could modify abnormal bone remodeling in OA.
High Immunogenicity of Intracellular Myelin Oligodendrocyte Glycoprotein Epitopes
2002-07-01

Abstract Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS with associated axonal loss. There is strong evidence for an autoimmune pathogenesis driven by myelin-specific T cells. Myelin oligodendrocyte glycoprotein (MOG) induces a type of experimental autoimmune encephalomyelitis in animals which is very MS-like since there are demyelinating CNS lesions and axonal loss. This underscores the potential role of MOG in MS pathogenesis. We performed a T cell reactivity pattern analysis of MS patients at the onset of relapse or progression of neurological deficits and controls that were stratified for the genetic risk factor HLA-DRB1*1501. For the first time, we show that there is an HLA-DR-restricted promiscuous dominant epitope for CD4+ T cells within the transmembrane/intracellular part of MOG comprising aa 146–154 (FLCLQYRLR). Surprisingly, controls had broader T cell reactivity patterns toward MOG peptides compared with MS patients, and the transmembrane and intracellular parts of MOG were much more immunogenic compared with the extracellular part. Measurements of in vitro binding affinities revealed that HLA-DRB1*1501 molecules bound MOG 146–154 with intermediate and HLA-DRB1*0401 molecules with weak affinities. The binding of MOG 146–154 was comparable or better than myelin basic protein 85–99, which is the dominant myelin basic protein epitope in context with HLA-DRB1*1501 molecules in MS patients. This is the first study in which the data underscore the need to investigate the pathogenic or regulatory role of the transmembrane and intracellular part of MOG for MS in more detail.
Supernumerary marker chromosomes derived from chromosome 15: analysis of 32 new cases
2002-07-01

Small supernumerary marker chromosomes (SMC) are a heterogeneous group of chromosomes with an estimated frequency of approximately 0.14–0.72 per 1000 newborns and higher frequencies in particular populations such as the mentally retarded or infertile males. With a frequency of about 50%, derivatives of chromosome 15 represent the most common SMC. Here we present the results of a detailed analysis of 32 SMC(15) carriers who were ascertained in pre‐ or post‐natal routine cytogenetic diagnostics. SMC(15) with euchromatic content led to mental and psychomotor retardation. In contrast, SMC(15) without euchromatin were found to have no influence on the carrier's phenotype but were detected with a high incidence among infertile males. The majority of SMC(15) are pseudodicentric homologous rearrangements. Based on our investigations a further characterization of der(15) was possible.
An Autoreactive γδ TCR Derived from a Polymyositis Lesion
2002-07-01

Abstract To investigate the role of γδ T cells in human autoimmune disease we expressed and characterized a γδ TCR from an autoimmune tissue lesion. The TCR was first identified in a rare form of polymyositis characterized by a monoclonal infiltrate of γδ T cells which invaded and destroyed skeletal muscle fibers. The Vγ1.3-Jγ1-Cγ1/Vδ2-Jδ3 TCR cDNA of the original muscle invasive γδ T cell clone was reconstructed from unrelated cDNA and transfected into the mouse hybridoma BW58α−β−. Appropriate anti-human γδ TCR Abs stimulated the TCR transfectants to produce IL-2, thus demonstrating that the human γδ TCR functionally interacted with murine signaling components. The transfected Vγ1.3/Vδ2 TCR recognized a cytosolic protein expressed in cultured human myoblasts and TE671 rhabdomyosarcoma cells. The Ag was recognized in the absence of presenting cells. Using a panel of control γδ TCR transfectants with defined exchanges in different positions of both TCR chains, we showed that the γδ TCR recognized its Ag in a TCR complementarity-determining region 3-dependent way. To our knowledge, this is the first example of a molecularly defined γδ TCR directly derived from an autoimmune tissue lesion. The strategy used in this study may be applicable to other autoimmune diseases.
Identification ofChlamydia pneumoniae-Derived Mouse CD8 Epitopes
2002-07-01

ABSTRACT Chlamydia pneumoniae is a common intracellular human pathogen that has been associated with several severe pathological conditions, including coronary heart disease and atherosclerosis. There is no vaccine against C. pneumoniae infection, but CD8 + T cells have been shown to be crucial for protection during experimental infection. However, the effector functions and epitope specificity of the protective CD8 + T cell remain unknown. The aim of this study was to identify C. pneumoniae -derived mouse CD8 epitopes by using a recent epitope prediction method. Of four C. pneumoniae proteins (the major outer membrane protein, outer membrane protein 2, polymorphic outer membrane protein 5, and heat shock protein 60), 53 potential CD8 + T-cell epitopes were predicted by H-2 class I binding algorithms. Nineteen of the 53 peptides were identified as CD8 epitopes by testing for induction of a cytotoxic response after immunization. To test whether the predicted epitopes are naturally processed and presented by C. pneumoniae -infected cells, we generated a panel of seven peptide-specific cytotoxic T lymphocyte lines that were subsequently tested for recognition of C. pneumoniae -infected target cells. By using this strategy, we were able to identify three C. pneumoniae CD8 epitopes that were, indeed, processed and presented on infected cells. Identification of these natural CD8 epitopes provides tools for characterization of CD8 + T-cell function in vivo and generation of epitope-specific prevention strategies.
Advances in pathogenic concepts and therapeutic agents in Rasmussen’s encephalitis
2002-07-01

Rasmussen's encephalitis is a rare inflammatory brain disease which occurs mainly in children and is characterised by affection of only one hemisphere. Pathogenetic concepts have considered three different, not mutually exclusive, key factors contributing to the initiating or perpetuating events in the central nervous system. These include viruses, autoimmune antibodies and autoimmune cytotoxic T lymphocytes. Based on these concepts, different therapeutic strategies have been pursued, such as antiviral agents, plasmapheresis, immuno-adsorption, immunosuppression or immunomodulation with intravenous immunoglobulins. However, due to the lack of larger studies, to date there is no established therapeutic strategy of this devastating disease. An overview of the current state of immunepathogenic concepts for Rasmussen's encephalitis is given and past and present treatment attempts are discussed, including an outline of future perspectives. An opinion on symptomatic treatment with anticonvulsive drugs is included.
Complete asymptomatic thrombosis and resorption of a congenital giant intracranial aneurysm
2002-07-01

✓ Intracranial aneurysms in infants are rare, but are associated with a high risk of rupture and subarachnoid hemorrhage. The authors report a case of an incidentally diagnosed, probably congenital, asymptomatic giant aneurysm of the posterior communicating artery in a 9-month-old girl, which completely thrombosed following a diagnostic superselective angiography without any neuropathological incident. Follow-up magnetic resonance imaging revealed that the aneurysm decreased further in size and was largely resorbed within 3 years after the initial finding. In single cases the natural history of congenital giant aneurysms may be better than previously assumed.
Extranodal marginal zone B cell lymphoma of MALT type involving the mucosa of both the urinary bladder and stomach
2002-07-01

Primary lymphoma of the urinary bladder is a very rare tumour. A bladder tumour was found in a 57 year old man with obstructive dysuria. It was found by histological and immunohistohistochemical investigation to be an extranodal marginal zone B cell lymphoma. Lymphoepithelial lesions were absent, but were found in a clinically silent gastric lymphoma discovered four weeks later during staging investigations; this gastric lymphoma was negative for Helicobacter pylori by breath test and molecular biological analysis. Sequencing of the clonal immunoglobulin heavy chain gene in both tumours indicated the same precursor cell, of follicular or post follicular origin. In synopsis, the data suggested that this was a case of primary lymphoma of the bladder with involvement of the stomach. The application of a chromosome 3 specific alpha satellite probe revealed trisomy 3. A tumour with these characteristics arising as a lymphoma of the bladder with a metachronous involvement of the gastric mucosa has not been described previously.
Medroxyprogesterone acetate versus norethisterone: effect on estradiol-induced changes of markers for endothelial function and atherosclerotic plaque characteristics in human female coronary endothelial cell cultures
2002-07-01

E(2) can positively influence various markers of endothelial function. Addition of MPA or NET can elicit different effects, which has been demonstrated for the first time in human coronary cell cultures. No impact was found on markers representing primarily vasotonus and thrombogenicity. In terms of MMP-1, which is crucial for atherosclerotic plaque stability, an enhancement of the beneficial E(2) effect was observed. However, regarding MCP-1, contrary effects of progestins cannot be excluded. This indicates that progestins may differ in their effects, particularly in the early stages of atherosclerosis, which has also been supported by other studies.
Functional Interaction of Region 4 of the Extracytoplasmic Function Sigma Factor FecI with the Cytoplasmic Portion of the FecR Transmembrane Protein of the Escherichia coli Ferric Citrate Transport System
2002-07-01

ABSTRACT Transcriptional regulation of the ferric citrate transport genes of Escherichia coli is initiated by the binding of ferric citrate to the outer membrane protein FecA. This binding elicits a signal that is transmitted by FecR across the cytoplasmic membrane into the cytoplasm, where the sigma factor FecI directs the RNA polymerase to the promoter upstream of the fecABCDE genes. An in vivo deletion analysis using a bacterial two-hybrid system assigned the interaction of the FecR and FecI proteins to the cytoplasmic portion of the FecR transmembrane protein and region 4 of FecI. Missense mutations randomly generated by PCR were localized to region 4 of FecI, and the mutants were impaired with regard to the interaction of FecR with FecI and fecB-lacZ transcription. The cloned region 4 of FecI interfered with fecB-lacZ transcription. Interaction of N-proximal regions of predicted FecR homologs with region 4 of predicted FecI homologs of Pseudomonas aeruginosa was demonstrated. The interaction was specific in that only cognate protein pairs interacted with each other; no interactions occurred between heterologous combinations of the P. aeruginosa proteins and between a P. aeruginosa FecI homolog and E. coli FecR. The results demonstrate that region 4 of FecI specifically binds FecR and that this binding is necessary for FecI to function as a sigma factor.
MHC Gene Related Effects on Microglia and Macrophages in Experimental Autoimmune Encephalomyelitis Determine the Extent of Axonal Injury
2002-07-01

Myelin‐oligodendrocyte‐glycoprotein (MOG)‐induced experimental autoimmune encephalomyelitis (EAE) in rats is a chronic inflammatory demyelinating disease of the central nervous system (CNS) strongly mimicking multiple sclerosis (MS). We determined the involvement of macrophages and microglia in the lesions of MOG‐EAE in relation to different major histocompatibility complex (MHC, RT1 in rat) haplotypes. We used intra‐RT1 recombinant rat strains with recombinations between the RT1 a and RT1 u haplotypes on the disease permissive LEW non‐MHC genome. Activated microglia and macrophages were identified morphologically and by expression of ED1 and allograft inhibitory factor‐1 (AIF‐1), and differentiated by their morphological phenotype. White matter lesions contained more macrophages and less microglia compared to grey matter lesions. Similarly active lesions were mainly infiltrated by macrophages, while microglia were abundant in inactive demyelinated plaques. In addition, we found a highly significant genetic association between a macrophage or microglia dominated lesional phenotype, which was independent from location and activity of the lesions. This was not only the case in demyelinating plaques of chronic EAE, but also in purely inflammatory lesions of acute passive transfer EAE. Rat strains with an u‐haplotype in both the Class II and the telomeric non‐classical Class I region revealed inflammatory and demyelinating lesions, which were dominated by activated microglia. The a‐haplotype in any of these regions was associated with macrophage dominated lesions. A comparison of lesions, exactly matched for stages of demyelinating activity in these different rat strains, showed that in spite of a similar extent of demyelination, axonal injury was significantly less in microglia compared to macrophage dominated lesions. Thus, our studies document a genetic influence of the MHC‐region on the relative contribution of macrophages versus microglia in the pathogenesis of EAE.