bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major histocompatibility complex class I presentation of exogenously acquired minor alloantigens initiates skin allograft rejection
Authors: Oukka Mohamed , Galou Maria , Belkaid Yasmine , Tricotet Vivianne , Riche Nicole , Reynes Michel , Kosmatopoulos Konstadionos 
Published: March 2007

AbstractMajor histocompatibility complex (MHC) class I molecules present peptides from endogenous proteins. However, in some cases class I‐restricted peptides can also derive from exogenous antigens. This MHC class I exogenous presentation could be involved in minor histocompatibility antigen (mHAg)‐disparate allograft rejection when donor alloantigens are not expressed in graft antigen‐presenting cells (APC) that initiate the rejection mechanism. Here we addressed this question by using a skin graft experimental model where donors (H‐2b or H‐2d Tgβ‐gal mice) expressed the mHAg like β‐galactosidase (β‐gal) in keratinocytes but not in Langerhans' cells (LC) which have an APC function. Rejection of Tgβ‐gal skin by a β‐gal‐specific CD8 cytotoxic T lymphocyte (CTL) effector mechanism should require presentation by donor and/or recipient LC of MHC class I‐restricted peptides of exogenous β‐gal shed by keratinocytes. Indeed, our results showed that 1) H‐2b Tgβ‐gal skin was rejected by H‐2bxs and H‐2bxd recipients; 2) rejection was mediated by β‐gal‐specific CD8+ CTL effectors; and 3) H‐2bxd mice having rejected H‐2b Tgβ‐gal skin generated β‐gal‐specific CTL restricted by H‐2b and H‐2d class I molecules and rejected subsequently grafted H‐2d Tgβ‐gal skin in an accelerated fashion, demonstrating that recipient LC have presented exogenous β‐gal‐derived MHC class I epitopes. These results lead to the conclusion that MHC class I exogenous presentation of donor mHAg can initiate allograft rejection.
Immunization with immune complex alters the repertoire of antigen‐reactive B cells in the germinal centers
Authors: Nie Xiaobo , Basu Subhendu , Cerny Jan 
Published: March 2007

AbstractThe differentiation of memory B cells in germinal centers (GC) is selectively enhanced upon administration of antigen‐antibody complexes. To characterize the repertoire of this response, we examined the rearranged immunoglobulin heavy chain variable (VH) genes from mouse splenic GC after a single immunization with either antigen, nitrophenyl (NP) hapten coupled to keyhole limpet hemocyanin, or with a preformed complex of antigen with a monoclonal anti‐NP antibody of γ1 isotype. Among antigen‐immunized mice, NP‐reactive GC B cell populations in the antigen‐induced GC consisted mostly of cells expressing the canonical V186.2 gene which contained, on average, 0.8 point mutations/VH gene by day 8 after immunization. These results are indicative of the beginning of somatic hypermutation and consistent with previously published analyses of NP antigen‐driven GC. In contrast, the NP‐specific B cells in GC that were elicited by administration of immune complex represented a heterogeneous cell population expressing nine different germ‐line segments of the V186.2/V3 (J558) gene family, i.e. V23, V24.8, C1H4, V3, CH10, V165.1, V102, V671.5 and V186.2. Moreover, the average frequency of mutations in these genes was 1.7, reaching up to 4 mutations/VH in some GC. Administration of the antigen NP in complex with specific antibody apparently alters the process of interclonal competition in the GC and results in loss of dominance by V186.2+ cells and nearly stochastic representation of diverse clono‐types. These results suggest an important feedback regulation of the B cell repertoire by antibody and indicate a role for immune complexes in the activation of somatic hypermutation.
Anti‐apoptotic signals of granulocyte‐macrophage colony‐stimulating factor are transduced via Jak2 tyrosine kinase in eosinophils
Authors: Simon Hans‐Uwe , Yousefi Shida , Dibbert Birgit , Levi‐Schaffer Francesca , Blaser Kurt 
Published: March 2007

AbstractCytokine‐mediated inhibition of eosinophil apoptosis is a mechanism causing tissue eosinophilia. Previously published work suggested that activation of the Lyn‐Ras‐Raf‐1‐MAP kinase pathway is obligatory for prevention of eosinophil apoptosis by eosinophil hematopoietins. We demonstrate herein that activation of freshly isolated human blood eosinophils by granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is associated with increased tyrosine phosphorylation of Jak2. The tyrosine kinase blocker, tyrphostin B42, prevented activation of Jak2 but not Lyn, suggesting that Jak2 is the specific target for tyrphostin B42 in eosinophils. In addition, since Lyn remained unaffected by tyrphostin B42, it is unlikely that Jak2 is required for Lyn activation in this model. To test whether tyrosine phosphorylation of Jak2 is linked to GM‐CSF‐mediated prolonged eosinophil survival, we determined the effect of tyrphostin B42 on eosinophil viability and apoptosis. Prevention of Jak2 activation by tyrphostin B42 was associated with the inability of GM‐CSF to prevent eosinophil apoptosis. These data suggest that disruption of not only the Lyn‐Ras‐Raf‐1‐MAP kinase but also the Jak‐STAT pathway blocks the ability of eosinophil survival factors to prevent apoptosis in eosinophils.
High‐resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization
Authors: Jönsson Göran , Staaf Johan , Olsson Eleonor , Heidenblad Markus , Vallon‐Christersson Johan , Osoegawa Kazutoyo , de Jong Pieter , Oredsson Stina , Ringnér Markus , Höglund Mattias , Borg Åke 
Published: March 2007

AbstractA BAC‐array platform for comparative genomic hybridization was constructed from a library of 32,433 clones providing complete genome coverage, and evaluated by screening for DNA copy number changes in 10 breast cancer cell lines (BT474, MCF7, HCC1937, SK‐BR‐3, L56Br‐C1, ZR‐75‐1, JIMT1, MDA‐MB‐231, MDA‐MB‐361, and HCC2218) and one cell line derived from fibrocystic disease of the breast (MCF10A). These were also characterized by gene expression analysis and found to represent all five recently described breast cancer subtypes using the “intrinsic gene set” and centroid correlation. Three cell lines, HCC1937 and L56BrC1 derived from BRCA1 mutation carriers and MDA‐MB‐231, were of basal‐like subtype and characterized by a high frequency of low‐level gains and losses of typical pattern, including limited deletions on 5q. Four estrogen receptor positive cell lines were of luminal A subtype and characterized by a different pattern of aberrations and high‐level amplifications, including ERBB2 and other 17q amplicons in BT474 and MDA‐MB‐361. SK‐BR‐3 cells, characterized by a complex genome including ERBB2 amplification, massive high‐level amplifications on 8q and a homozygous deletion of CDH1 at 16q22, had an expression signature closest to luminal B subtype. The effects of gene amplifications were verified by gene expression analysis to distinguish targeted genes from silent amplicon passengers. JIMT1, derived from an ERBB2 amplified trastuzumab resistant tumor, was of the ERBB2 subtype. Homozygous deletions included other known targets such as PTEN (HCC1937) and CDKN2A (MDA‐MB‐231, MCF10A), but also new candidate suppressor genes such as FUSSEL18 (HCC1937) and WDR11 (L56Br‐C1) as well as regions without known genes. The tiling BAC‐arrays constitute a powerful tool for high‐resolution genomic profiling suitable for cancer research and clinical diagnostics. © 2007 Wiley‐Liss, Inc.
Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas
Authors: Winnes Marta , Mölne Lena , Suurküla Mart , Andrén Ywonne , Persson Fredrik , Enlund Fredrik , Stenman Göran 
Published: March 2007

AbstractFusion of the CREB regulated transcription coactivator CRTC1 (a.k.a. MECT1, TORC1, or WAMTP1) to the Notch coactivator MAML2 is a characteristic feature of low‐grade mucoepidermoid carcinomas of salivary and bronchial glands. The CRTC1–MAML2 fusion protein acts by inducing transcription of cAMP/CREB target genes, and this activity is crucial for the transforming properties of the protein. Here we show that the CRTC1–MAML2 gene fusion is also frequent in benign hidradenomas of the skin. FISH and RT‐PCR analyses revealed that hidradenomas are genetically heterogeneous, and that 10 of the 20 tumors analyzed (50%) contained the CRTC1–MAML2 gene fusion and expressed the resulting fusion transcript. Immunohistochemical analysis demonstrated expression of the fusion protein in the majority of tumor cells, including clear cells, poroid cells, and cells with epidermoid and ductal differentiation. In addition, we could show that all fusion‐positive tumors were morphologically distinguished by the presence of more or less abundant areas of clear cells whereas all fusion‐negative tumors lacked clear cells. Our findings thus demonstrate that the CRTC1–MAML2 gene fusion is frequent in hidradenomas and is associated with clear cell variants of this tumor. Taken together, the present and previous observations indicate that the CRTC1–MAML2 fusion is etiologically linked to benign and low‐grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity. © 2007 Wiley‐Liss, Inc.
Prominent oligodendrocyte genesis along the border of spinal contusion lesions
Authors: Tripathi Richa , McTigue Dana M. 
Published: March 2007

AbstractOligodendrocyte (OL) loss and axon demyelination occur after spinal cord injury (SCI). OLs may be replaced, however, by proliferating NG2+ progenitor cells. Indeed, new OLs have been noted in ventral white matter after SCI. Since tissue adjacent to lesion cavities is exposed to different mediators compared with outlying spared tissue, the authors used a rat SCI model to compare NG2 cell proliferation and OL genesis adjacent to lesion cavities with that in spared tissue closer to meninges. NG2 cells proliferated throughout the first week postinjury and accumulated along lesion borders, especially within gray matter. By 3 days postinjury (dpi), new OLs were detected throughout the cross‐sections; between 4 and 7 dpi, however, oligogenesis was restricted to lesion borders. New OLs derived from cells proliferating during 1–7 dpi increased dramatically by 14 dpi; most were located along lesion borders and in spared gray matter. Oligogenesis continued along lesion borders during the second week postinjury. Overall OL numbers were reduced at 3 dpi in spared tissue, but rebounded to normal levels by 14 dpi. Surprisingly, lesion borders maintained normal OL numbers at 3 dpi, which then rose to exceed preinjury levels at 7 and 14 dpi. These results indicate that oligogenesis is protracted after SCI and leads to increased OL numbers. Most new OLs are formed in regions of greatest NG2 cell proliferation. Thus, the adult spinal cord spontaneously develops a dynamic gliogenic zone along lesion borders. © 2007 Wiley‐Liss, Inc.
Increase in the number of fenestrae in mouse endothelial liver cells by altering the cytoskeleton with cytochalasin B
Authors: Steffan Anne-Marie , Gendrault Jean-Louis , Kirn André 
Published: March 2007

Endothelial cells of the hepatic sinusoid isolated from mice livers and maintained in culture display typical fenestrae grouped in sieve plates. Treatment with cytochalasin B led to no significant change in the mean diameter of the fenestrae but to an increase in their number and in the porosity of the cells (percentage of the cellular surface opened by the fenestrae) which attained up to 300% of that of the controls. Scanning electron microscopic observations of Triton-extracted cells revealed that these modifications were related to an alteration of the cytoskeleton. The effect of cytochalasin B could be reversed; 3 hr after removal of the drug, the cells recovered their original aspect with sieve plates scattered over their surface.
These observations demonstrate that endothelial fenestrae are inducible structures and that the cytoskeleton seems to be involved in their formation.
Renal response to atrial natriuretic peptide in patients with advanced liver cirrhosis
Authors: Salerno Francesco , Badalamenti Salvatore , Incerti Pierluigi , Capozza Loredana , Mainardi Laura 
Published: March 2007

Sodium retention in liver cirrhosis is thought to be due to, among other things, lack of a natriuretic factor or failure to respond to one. α-Human-atrial natriuretic peptide is a peptide that accounts partly or entirely for the circulating natriuretic activity in man.
In the present study, we have evaluated the effects of the bolus administration of synthetic α-human-atrial natriuretic peptide (1 μg per kg) to patients with liver cirrhosis and variable degrees of sodium retention, α-Human-atrial natriuretic peptide induced rapid and marked increases of diuresis and natriuresis in patients without sodium retention or with moderate retention. The results were comparable to those obtained in six healthy control subjects. Conversely, the diuretic and natriuretic effects of α-human-atrial natriuretic peptide were attenuated or completely blunted in patients with avid sodium retention. The two groups of patients differed not only in basal sodium excretion, but also in plasma renin activity and in plasma aldosterone levels, suggesting that the reduced responsiveness to atrial natriuretic peptide might be due to excessive antagonism by antinatriuretic factors. The direct relationship between baseline sodium excretion rate and that stimulated by human-atrial natriuretic peptide administration was consistent with this interpretation. In none of the subjects did plasma renin activity peptide and cortisol levels change after human-atrial natriuretic peptide, while plasma aldosterone slightly declined in cirrhotics. Blood pressure fell after the administration of the peptide, with the drop greater in cirrhotic than in normal subjects. These data show that the hormonal and the vascular effects of human-atrial natriuretic peptide are not blunted in cirrhotics. Since angiotensin II plays a central role in sustaining blood pressure in patients with advanced liver cirrhosis, the marked drop in blood pressure has been tentatively ascribed to the specific ability of atrial natriuretic peptide to antagonize angiotensin, but other mechanisms cannot be excluded.
In conclusion, these data suggest that renal unrespon-siveness to atrial natriuretic peptide develops in patients with liver cirrhosis during the course of the disease and is strictly related to the severity of sodium retention.
Oral charcoal therapy of congenital erythropoietic porphyria
Authors: Tishler Peter V. 
Published: March 2007

Günther’s disease, or congenital erythropoietic porphyria, is a rare autosomal recessive disorder of heme biosynthesis characteristically associated with diminished uroporphyrinogen III cosynthetase activity. Disfiguring photomutilation starts in childhood. Avoidance of sunlight has been the only sure way to prevent or retard photosensitivity. The treatments that have been tried have had limited success. A partial benefit after splenectomy has been reported, but there is little evidence of specific, long-term improvement. Haining and colleagues first reported suppression of bone marrow release of porphyrins by induced polycythemia, supporting the notion that disease activity can be modulated by diminishing porphyrin overproduction at the source (i.e., the bone marrow). Recently, Piomelli et al. reported complete suppression of symptoms in a 10-year-old child treated from birth with transfusion therapy and with splenectomy. Another approach is the use of orally administered sorbents such as charcoal and cholestyramine, which bind porphyrins in vitro, to retard enteral absorption of endogenous porphyrins excreted into the gut lumen. Cholestyramine has been reported to reduce photocutaneous sensitivity in porphyria cutanea tarda and to reverse the hepatic lesion in protoporphyria.
In this study, we compared different treatments for progressive photomutilation in a patient with congenital erythropoietic porphyria. The effects of short-term hypertransfusion were evaluated, as was the efficacy of long-term transfusion therapy over a two-year period. To test the potential usefulness of porphyrin-binding drugs, we estimated the enteral absorption of endogenous porphyrins in the proximal small bowel and monitored the effects on tissue and excreted porphyrins of short-term oral challenges with activated charcoal (ActaChar) and with cholestyramine. Charcoal therapy was more effective than cholestyramine and therefore was subsequently administered for a long period. The data collected allow comparison of long-term charcoal therapy and long-term blood-transfusion therapy. Treatment with charcoal for nine months lowered porphyrin levels in plasma and skin and resulted in a complete clinical remission during therapy. (A preliminary report on part of this work has appeared elsewhere).
Prognostic indicators in alcoholic cirrhotic men
Authors: Gluud Christian , Henriksen Jens H. , Nielsen Gert 
Published: March 2007

The relationships between portal pressure, liver function and clinical variables on one hand and development of variceal hemorrhage and death on the other were investigated in 58 men with newly diagnosed alcoholic cirrhosis. Portal pressure was determined during hepatic vein catheterization as wedged minus free hepatic vein pressure, and median pressure was 14 mm Hg (range = 3 to 26 mm Hg). Fourteen of 31 patients (45%) had esophageal varices at upper gastrointestinal endoscopy (the size being considered large in nine patients).
During follow-up (median = 31 months; range = 2 to 51 months), 12 patients (21%) developed variceal hemorrhage. Applying Cox’s regression analysis, information about previous variceal bleeding (p = 0.0046), large varices at endoscopy (p = 0.012), hepatic vein pressure gradient (p = 0.0056) and indocyanine green clearance (p = 0.038) all contained significant prognostic information regarding development of variceal hemorrhage, even when easily obtained variables with known prognostic information were included [modified Child-Turcotte’s criteria and incapacitation index (a weighted sum of days without normal health)].
During follow-up, 17 patients (29%) died. Applying Cox’s regression analysis, large varices at endoscopy (p = 0.012) and hepatic vein pressure gradient (p = 0.019) contained significant prognostic information regarding death, in addition to the information contained in the modified Child-Turcotte’s criteria and incapacitation index. In conclusion, prediction of prognosis in alcoholic cirrhotic men may be significantly improved by information about size of esophageal varices and level of portal pressure.
A new variant of type IV glycogenosis: Deficiency of branching enzyme activity without apparent progressive liver disease
Authors: Greene Harry L. , Brown Barbara I. , McClenathan Daniel T. , Agostini Rocco M. , Taylor Suzanne R. 
Published: March 2007

Type IV glycogenosis is due to branching enzyme deficiency and is usually manifested clinically by progressive liver disease with cirrhosis and hepatic failure between the second and fourth years of life. We describe a 5-year-old boy who, following an acute febrile illness at 2 years of age, was first noted to have hepatomegaly with mildly elevated serum transaminase levels. Liver biopsy revealed hepatic fibrosis with periodic-acid Schiff-positive, diastase-resistant inclusions in hepatocytes and fibrillar inclusions characteristic of amylopectin by electron microscopy. Enzymatic assay revealed deficient hepatic branching enzyme activity with normal activity of glucose-6-phosphatase, debranching enzyme and phosphorylase activities. During the succeeding 3 years, he grew and developed normally with apparent resolution of any clinical evidence of liver disease and only intermittent elevation in serum transaminase levels associated with fever and prolonged fasting. Repeat liver biopsy at 4 years of age showed persistence of scattered hepatocellular periodic-acid Schiff-positive, diastase-resistant inclusions, but no progression of hepatic fibrosis in spite of persistent deficiency of hepatic branching enzyme activity. Skeletal muscle and skin fibroblasts from the patient also showed deficient enzyme activity. Skin fibroblasts from both parents exhibited half the normal control activity, suggesting a heterozygote state.
This is the first documented patient with deficiency of branching enzyme but without evidence of progressive hepatic disease. This patient, coupled with reports of other patients with late onset hepatic or muscle disease with branching enzyme deficiency, suggests that the defect resulting in Type IV glycogen storage disease is more heterogenous and possibly more common than previously suspected.
Cholesterol nucleation-influencing activity in t-tube bile
Authors: Groen Albert K. , Stout Jan P. J. , Drapers Jan A. G. , Hoek Frans J. , Grijm Rob , Tytgat Guido N. J. 
Published: March 2007

Nucleation-influencing activity was determined in T-tube bile samples derived from patients with obstructive jaundice. Since native T-tube bile samples do not nucleate, nucleation-influencing activity was determined by measuring the influence of T-tube bile on the nucleation time of model bile. In the assay, T-tube bile was mixed with model bile, and the nucleation time of this mixture was compared with the nucleation time of a model bile supplemented with the same amount of lipid as present in the bile sample. The results were expressed as ratio of the nucleation time of the mixture and the nucleation time of the control (NTm/NTc). There was a significant difference (p < 0.01) between bile samples from patients with cholesterol gallstones and samples from patients with biliary obstruction due to other causes. More than 80% of the 33 samples from eight patients with stones were nucleation-promoting (NTm/NTc ≤ 0.6). Of the 40 bile samples from patients without stones, 7 were nucleation-promoting, 25 had no effect (NTm/NTc = 0.8 to 1.2) and 8 bile samples were nucleation-inhibiting (NTm/NTc ≥ 1.4). There was no correlation between the lipid or protein content of a T-tube bile sample and its nucleation-influencing activity.
The presence of both nucleation-promoting and nucleation-inhibiting activity in the same T-tube bile was demonstrated by chromatography on concanavalin A-Sepharose. More than 75% of the biliary protein did not bind to the column. This fraction showed nucleation-inhibiting activity. However, nucleation inhibitor present in this fraction was unstable, and after destruction of the inhibitor, the fraction showed promoting activity. This suggests that, in addition to inhibitor, this fraction also contained nucleation-promoting activity. About 10% of biliary protein did bind to concanavalin A-Sepharose and could be eluted with α-D-methylmannopyranoside. This fraction always contained nucleation-promoting activity. Both this factor and the nucleation-promoting factor that did not bind to concanavalin A were resistant to treatment with the proteolytic enzyme pronase. We conclude that T-tube bile contains at least three different classes of nucleation-influencing factors. The balance between promoting and inhibiting activity in a particular bile sample determines the overall nucleation-influencing effect of the sample. In bile from cholesterol gallstone patients, this balance is shifted towards promoting activity. One of the promoting factors probably is a glucose-/mannose-containing glycoprotein.