[Multifocal angiosarcoma of the gastrointestinal tract:a case report].

An 80-year-old man presented to our hospital with complaints of tarry stool and shortness of breath. A blood test confirmed marked anemia. On abdominal contrast-enhanced computed tomography, neither hemorrhagic lesions nor tumorous lesions could be pointed out.

[Neuroendocrine tumor of the terminal ileum observed by magnifying endoscopy with narrow-band imaging: a case report].

We report the case of an 88-year-old woman with localized intestinal obstruction caused by a midgut neuroendocrine tumor (NET) without endocrine symptoms. She was referred to our hospital for lower abdominal pain. Abdominal enhanced computed tomography revealed a thickened wall in the terminal ileum with dilated small bowel and multiple hepatic metastases upstream.

[Obstructive colitis following the ingestion of laxatives during bowel preparation for colonoscopy: a report of two cases].

The first case of obstructive colitis (OC) was observed in a 71-year-old man who presented to our hospital complaining of frank blood in the stool. After receiving a laxative for bowel preparation, he complained of lower abdominal pain. Colonoscopy revealed a circumferential tumor at the rectosigmoid junction.

Treatment of a colonic Dieulafoy lesion with endoscopic hemoclipping.

A 39-year-old man presented to our hospital with massive haematochezia and dizziness. A colonoscopy indicated the presence of an abnormal visible vessel with an adherent clot at the ascending colon. No mucosal abnormality surrounding the lesion was noted.

Late Migration of Covered Metal Stent to the Stomach Through a Spontaneous Choledochoduodenal Fistula in a Patient With Malignant Biliary Obstruction.

We report a case in which a spontaneous choledochoduodenal fistula occurred after biliary covered self-expanding metal stent (SEMS) placement and a late transfistula migration of the stent in a patient with malignant distal biliary obstruction. A partially covered WallFlex biliary stent (Boston Scientific) was appropriately implanted in the common bile duct. Subsequently the patient received chemotherapy with gemcitabine.

Indirect and direct evidence for DNA double-strand breaks in hypermutating immunoglobulin genes.

The generation of a diverse antigen receptor repertoire is fundamental for the functionality of the adaptive immune system. While the V(D)J recombination process that generates the primary antigen receptor repertoire is understood in great detail, it is still unclear by which mechanism immunoglobulin (Ig) genes are further diversified by somatic hypermutation. Using mouse strains that carry a non-functional, pre-defined V(H)D(H)J(H) gene segment in their IgH locus we demonstrate DNA double-strand breaks (DSBs) in and around V(H)D(H)J(H) in B cells undergoing somatic hypermutation.

DNA double-strand breaks in immunoglobulin genes undergoing somatic hypermutation.

How rearranged immunoglobulin (Ig) genes are further diversified by somatic hypermutation is unknown. Using VDJ passenger Ig heavy chain (IgH) knockin mouse strains, we now demonstrate a high frequency of DNA double-strand breaks (DSBs) in the targeted VDJ passenger gene of germinal center (GC) B cells. These DSBs parallel the distribution of mutations in the targeted hypermutation domain and are found preferentially at RGYW motifs, the intrinsic hot spots of somatic hypermutation.

Tuning somatic hypermutation by transcription.

The dependence of somatic hypermutation on transcription was studied in three mutant immunoglobulin heavy chain (IgH) insertion mice in which a targeted non-functional VHB1-8 passenger transgene was either placed under the transcriptional control of a truncated DQ52 promoter (p delta), its own RNA polymerase II dependent IgH promoter (pII) or a RNA polymerase I dependent promoter (pI). The relative mutation-frequency of the VHB1-8 passenger transgene in memory B cells of p delta, pI and pII mice (7%, 60% and 100%) correlated with the relative levels of transgene-specific pre-mRNA expressed in germinal center B cells isolated from the mutant mice (8%, 72% and 100%, respectively). These data indicate that the mutation load of rearranged Ig genes can be tuned by transcription.

Somatic hypermutation in the heavy chain locus correlates with transcription.

Three mutant immunoglobulin heavy chain (IgH) insertion mice were generated in which a targeted nonfunctional IgH passenger transgene was either devoid of promoter (pdelta) or was placed under the transcriptional control of either its own RNA polymerase II-dependent IgH promoter (pII) or a RNA polymerase I-dependent promoter (pI). While the transgene mutation-frequency (0.85%) in memory B cells of pI mice was reduced compared to that in pII mice (1.

Hypermutation of immunoglobulin genes in memory B cells of DNA repair-deficient mice.

To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vlambda1 light chain genes from naive and memory B cells in DNA repair-deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation.

Recent translocation of variable and diversity segments of the human immunoglobulin heavy chain from chromosome 14 to chromosomes 15 and 16.

We studied the organization and origin of three orphon regions, VH-F, D5-a, and D5-b, of the human immunoglobulin heavy-chain gene using yeast artificial chromosomes. VH-F and two D5 regions were mapped to chromosome bands 16p11 and 15q11-q12, respectively, by using human/rodent somatic cell hybrids and fluorescence in situ hybridization. No D5 segments were found on chromosome 14, in contradiction to previous reports.

Comparison and evolution of human immunoglobulin VH segments located in the 3' 0.8-megabase region. Evidence for unidirectional transfer of segmental gene sequences.

Nucleotide sequences of 64 VH segments within the 3' 0.8-megabase region of the human immunoglobulin germ line VH locus were compared with trace evolution of human VH segments. Based on alignment of the deduced amino acid sequences of 37 functional germ line VH segments, a phylogenetic tree was generated using the neighbor-joining method.

Structural analysis of the human VH locus using nonrepetitive intergenic probes and repetitive sequence probes. Evidence for recent reshuffling.

The organization and evolution of the 0.8-Mb JH-proximal region in the human Ig VH locus were studied by mapping DNA fragments hybridized to non-repetitive intergenic probes and by determination of the content and distribution of repetitive sequences. Southern blot analysis of cloned DNA covering the 0.

The human S mu bp-2, a DNA-binding protein specific to the single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region.

We have cloned the cDNA encoding the human homologue of S mu bp-2, which binds to single-stranded DNA with 5'-phosphorylated guanine-rich sequences related to the immunoglobulin mu chain switch (S mu) region. The deduced amino acid sequences of the mouse and human S mu bp-2 are 76.5% homologous and contain motifs conserved among helicases.

Isolation of cDNA encoding a binding protein specific to 5'-phosphorylated single-stranded DNA with G-rich sequences.

We have isolated the cDNA encoding a binding protein to the sequence motif of the immunoglobulin S mu region by the southwestern method. The binding protein designated S mu bp-2 specifically binds to 5'-phosphorylated single-stranded DNA containing 5'-G and GGGG stretches. The amino acid sequence deduced from the cDNA sequence showed that the S mu bp-2 belongs to the putative helicase superfamily which is involved in replication, recombination and repair.

Structure and physical map of 64 variable segments in the 3'0.8-megabase region of the human immunoglobulin heavy-chain locus.

We have constructed the physical map of the 0.8 megabase DNA fragment which contains the 3' 64 variable region (V) gene segments of the human immunoglobulin heavy chain (H) locus. The organization of the VH locus showed several features that indicate dynamic reshuffling of this locus.