A case report of primary gastric adult T cell lymphoma

A 70-year-old woman was admitted to our hospital for treatment of abdominal tumor. She had complained of left abdominal pain, body weight loss and slight fever. Upper gastrointestinal endoscopy revealed on profounding ulcerous and upheaval lesion from the upper part of gastric body to the antrum. The pathological diagnosis of the biopsy specimens was T-cell lymphoma and proviral DNA (GAG) of HTLV-I was demonstrated in the biopsy specimens. Although the patient was serologically positive for anti-human T-lymphotrophic virus type I (HTLV-I) antibody, there were no leukemia/lymphoma cells in the peripheral blood or systemic lymphadenopathy. Primary gastric Adult T-cell leukemia/lymphoma (ATLL) was diagnosed. Although she received chemotherapy, the response was poor. The prognosis of lymphoma-type ATL is known to be extremely poor. This disease is frequent in aged people. Although gastrointestinal involvement is frequent in ATLL, primary gastric ATLL is rare. We report this rare case with primary gastric ATLL and reviewing 13 cases previously reported.     

Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in rats: the roles of phosphatidylinositol 3-kinase and nitric oxide

Background

Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR) injury. Milrinone, a phosphodiesterase 3 inhibitor, has been reported to exhibit preconditioning properties against hepatic IR injury; however, its PostC properties remain unknown. This study investigated whether milrinone has PostC properties against hepatic IR injury and the roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS).

Materials and methods

Male Wistar rats were separated into six groups: (1) group S: animals that underwent sham operation without ischemia, (2) group C: ischemia followed by reperfusion with no other intervention, (3) group M: milrinone administered immediately after reperfusion, (4) group MW: wortmannin, a PI3K inhibitor, injected before milrinone administration, (5) group MN: l-NAME, a NOS inhibitor, injected before milrinone administration, and (6) group MD, milrinone administered 30 min after reperfusion. Except for group S, all groups underwent 1 h of warm ischemia of median and left lateral lobes, followed by 5 h of reperfusion. Biochemical liver function analysis and histologic examination were performed.

Results

Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, histologic damage scores, and apoptotic rate in group M were significantly lower than those in group C. The inhibition of PI3K or NOS prevented this protective effect. Milrinone administered 30 min after reperfusion did not show obvious protective effects.

Conclusions

Milrinone-induced PostC protects against hepatic IR injury when it is administered immediately after reperfusion, and PI3K and NOS may play an important role in this protective effect.     

Development of myeloid sarcoma after long-term methotrexate use for rheumatoid arthritis

Myeloid sarcoma (MS) in the complete absence of bone marrow disease is an extremely rare phenomenon. We report the case of a 78-year-old woman with multiple subcutaneous lung and liver nodules, including mediastinal and peritoneal lymph node swelling, who had been receiving methotrexate (MTX) for 10 years for rheumatoid arthritis (RA). She was initially diagnosed with ALK-negative anaplastic large cell lymphoma. After one course of an anthracycline-containing regimen, pathologic cells were identified as CD68 (Kp-1)-positive with myeloid-lineage tumor cells and abnormal karyotypes with 8q21 and 21q22. Subsequent treatment was changed to acute myelogenous leukemia (AML) induction chemotherapy. Although the lesions were partially reduced in size following treatment for lymphoma, complete response (CR) was obtained only after AML chemotherapy. The patient remained in CR over 3 years after the last chemotherapy. This case may indicate an association between long-term MTX use and MS. An early diagnosis and adequate therapy may be important for improving survival outcomes in MS. This report demonstrates that CD68 staining is important for the differential diagnosis of MS and lymphoma. Careful follow-up is necessary for this patient, who may be the first case of MS after methotrexate use for RA.     

Septin assemblies form by diffusion-driven annealing on membranes

Septins assemble into filaments and higher-order structures that act as scaffolds for diverse cell functions including cytokinesis, cell polarity, and membrane remodeling. Despite their conserved role in cell organization, little is known about how septin filaments elongate and are knitted together into higher-order assemblies. Using fluorescence correlation spectroscopy, we determined that cytosolic septins are in small complexes, suggesting that septin filaments are not formed in the cytosol. When the plasma membrane of live cells is monitored by total internal reflection fluorescence microscopy, we see that septin complexes of variable size diffuse in two dimensions. Diffusing septin complexes collide and make end-on associations to form elongated filaments and higher-order structures, an assembly process we call annealing. Septin assembly by annealing can be reconstituted in vitro on supported lipid bilayers with purified septin complexes. Using the reconstitution assay, we show that septin filaments are highly flexible, grow only from free filament ends, and do not exchange subunits in the middle of filaments. This work shows that annealing is a previously unidentified intrinsic property of septins in the presence of membranes and demonstrates that cells exploit this mechanism to build large septin assemblies.Septin filaments form rings, bars, and gauzes that serve as a scaffold at cell division sites; act to retract blebbed regions of membrane; and restrict diffusion between cell compartments (1–4). Septin function is required for cell division and viability in many eukaryotes whereas misregulation is associated with cancers and neurodegenerative disorders (5–8). Furthermore, septins mediate entry of both bacterial and fungal pathogens into host cells (9–11). In vivo, septin assembly is restricted both in time and in space through local activation of small GTPases such as Cdc42. Localized signaling leads to higher-order septin structures forming closely apposed to the plasma membrane at the plane of division, sites of polarity, and curved membranes (10, 12–14). Notably, eukaryotic cells of different geometries build higher-order septin assemblies of various shapes, sizes, and functions (4, 15, 16). Although septins are critical for spatial organization of cell plasma membranes, their assembly and disassembly dynamics are not understood (15).Electron microscopy (EM) studies of recombinant and immunoprecipitated Saccharomyces cerevisiae septins have shown that septins form nonpolar hetero-octameric rod-shaped complexes in high-salt buffers (>300 mM) and elongated filaments when dialyzed into low-salt buffers (<100 mM) (17, 18). Structural analyses of worm and mammalian septins have revealed that the heteromeric, rod-shaped complex is conserved (19–21). Thus, septin rods characterized to date contain two copies of each septin subunit assembled into a nonpolar, heteromeric complex (Fig. S1). Association of purified septin proteins with phosphoinositide-containing membrane monolayers placed on EM grids can promote the assembly of septin filaments in otherwise nonpermissive conditions such as high salt or the presence of mutant septins in the complex (22). A polybasic region in the N terminus of septin proteins as well as other surfaces of the septin protein have been proposed to be the basis for septin association with phosphoinositides; however, the functional role of membranes in filament formation is not yet known (22–24).Previous work has defined a possible starting state of assembly (the rod) and endpoint (filaments and gauzes); however, there is nothing known about how filaments elongate either in vivo or in vitro. Do septin filaments extend by stepwise addition of rods? Does addition occur from both ends of the filament? Can subunits be added in the middle and/or sides of a filament? Do septin filaments grow in the cytosol or on plasma membranes? Thus, it is still not known where filaments form in vivo, how filaments elongate, and how filaments are brought together to construct higher-order assemblies.The goal of this study was to identify the locations and mechanism of septin filament polymerization. Using fluorescence correlation spectroscopy (FCS), we observed that cytosolic septins are likely rods, not monomers or filaments. Using total internal reflection fluorescence (TIRF) microscopy, we found septins form short filaments on the plasma membrane and then long filaments and higher-order assemblies grow when filaments merge. We have called the process of short filaments coming together “annealing” as this has previously been described for F-actin in vitro (25). We reconstituted septin assembly, using purified proteins and supported lipid bilayers, and found that annealing is an intrinsic property of septins that occurs at very low protein concentrations in the presence of a supported phospholipid bilayer. Our results suggest that the plasma membrane concentrates septins and provides a platform for 2D diffusion that promotes polymerization.     

Epidemiology of colonic diverticula and recent advances in the management of colonic diverticular bleeding

There is the East-West paradox in prevalence and phenotype of colonic diverticula, but colonic diverticular bleeding (CDB) is the most common cause of acute lower gastrointestinal bleeding worldwide. Death from CDB can occur in elderly patients with multiple comorbidities, thus the management of CDB is clinically pivotal amid the aging populations in the East and West. Colonoscopy is the key modality for managing the condition appropriately; however, conventional endoscopic hemostasis by thermal coagulation and clipping cannot achieve the expected results of preventing early rebleeding and conversion to intensive intervention by surgery or transcatheter arterial embolization. Ligation therapy by endoscopic band ligation or endoscopic detachable snare ligation has emerged recently to enable more effective hemostasis for CDB, with an early rebleeding rate of approximately 10% and very rare conversion to intensive intervention. Ligation therapy might in turn reduce long-term rebleeding rates by eliminating the target diverticulum itself. Adverse events have been reported with ligation therapy including diverticulitis of the ascending colon in less than 1% of cases and perforation of the sigmoid colon in a few cases, thus more data are necessary to verify the safety of ligation therapy. Endoscopic hemostasis is indicated only for diverticulum with stigmata of recent hemorrhage (SRH), but the detection rates of SRH are relatively low. Therefore, efforts to increase detection are also key for improving CDB management. Urgent colonoscopy and triage by early contrast-enhanced computed tomography may be candidates to increase detection but further data are necessary in order to make a conclusion.     

Anatomical correlates of quality of life: Evidence from voxel‐based morphometry

Quality of life (QOL) has been defined in many ways, and these definitions usually emphasize happiness and satisfaction with life. Health‐related problems are known to cause lower QOL. However, the neural mechanisms underlying individual differences in QOL measured by questionnaire (QOLMQ) in young healthy subjects are unknown. QOL is essential to our well‐being, and investigation of the neural mechanisms underlying QOL in uncompromised subjects is obviously of great scientific and social interest. We used voxel‐based morphometry to investigate the association between regional gray matter volume (rGMV) and QOLMQ across the brain in healthy young adults (age, 21.4 ± 1.8 years) men (n = 88) and women (n = 68) in humans. We found significant negative relationships between QOLMQ and rGMV in a region in the left rostrolateral prefrontal cortex and regions in the dorsal part of the anterior cingulate gyrus and contingent cingulate regions. These findings show that structural variations in regions associated with processing of negative emotions such as fear and anger as well as those associated with evaluation of internally generated information are associated with QOLMQ. These findings suggest that these processes might be related to QOLMQ in healthy young adults. Hum Brain Mapp 35:1834–1846, 2014. © 2013 Wiley Periodicals, Inc.