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Makoto Saito,1 Kencho Miyashita,2 Yosuke Miura,3 Reiki Ogasawara,1 Minoru Kanaya,1 Koh Izumiyama,1 Akio Mori,1 Takeshi Kondo,1 Masanori Tanaka,1 Masanobu Morioka,1 Shinya Tanaka4 1Department of Internal Medicine and Hematology, Aiiku Hospital, Sapporo, Japan; 2Department of Gastroenterology, Aiiku Hospital, Sapporo, Japan; 3Department of Internal Medicine, Megumino Hospital, Eniwa, Japan; 4Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan Abstract: Colorectal follicular lymphoma (FL) occurs less frequently than duodenal-type FL, which is an established entity, and primary multiple FL only involving the colon is rare. Furthermore, the coexistence of lymphoma and multiple myeloma (MM) within the same patient is rare and the current study reports such a case. The patient was an asymptomatic 62-year-old man. He underwent colonoscopy screening, which revealed at least five polypoid tumors from the cecum to the rectum. Biopsy samples stained positive for CD20 and B-cell lymphoma 2 (BCL2) but stained negative for CD10, and fluorescence in situ hybridization analysis identified IGH/BCL2 in 95.2% of the tumor cells. Based on these findings, the patient was diagnosed with FL. On the bone marrow aspirate, the plasma cell count was 30% of all nucleated cells. Bence-Jones κ-type protein was detected by protein electrophoresis in serum and urine. The serum-free light chain κ/λ level was significantly elevated (484.3). Thus, the patient was also diagnosed with MM. Both FL and MM were targeted therapeutically; rituximab and bendamustine were effective for FL, and lenalidomide and low-dose dexamethasone were effective for MM. The patient was treated for 3years and 7months and, until now, was off-treatment for 4years without rapid progression of the two malignancies. Although both diseases are still present, the patient has maintained stable disease. Our findings suggest that lymphoma and MM should be targeted separately as independent hematological malignancies when they occur concurrently. Keywords: follicular lymphoma, colon, multiple myeloma, coexistence, treatment

Objective: Cells that are encapsulated into immunoprotective and implantable devices provide a means of enabling targeted, longterm, continuous, de novo synthesized delivery of very high levels of therapeutic molecules. In this study, we examined effects of polymer encapsulated glial cell line-derived neurotrophic factor (GDNF) secreting ARPE-19 cells on the in vitro viability of odontoblast-like cells (KN-3 cells) under normally lethal starvation conditions. Materials and methods: Devices (polymeric hollow fibers) were loaded with either GDNF-secreting ARPE-19 cells (GDNF-device) or non-modified ARPE-19 cells (ARPE-control device). KN-3 cell survival and function was quantified under starvation conditions when the cells were co-cultured with either control or GDNF devices. We further examined the specificity of GDNF by neutralizing the activity of GDNF with the soluble GDNF receptor (GFRα-1). Results: When KN-3 cells were co-cultured with either device under starvation, the cells exhibited a concentration gradient-dependent enhancement of survival in the area immediately surrounding the device. Similar survival benefits occurred when KN-3 cells were cultured in media previously used to maintain the cells encapsulated in the device. Because ARPE-19 cells also normally secrete low levels of VEGF, the maintenance medium from each device group was pretreated with soluble Flt-1 or soluble GFRα-1 to neutralize VEGF or GDNF. The survival of KN-3 cells was suppressed when cultured in VEGF-neutralized medium from ARPE-control devices, but not in that from GDNF-devices. In contrast, when GDNF was neutralized with soluble GFRα-1, the survival of KN-3 cells was intensely suppressed. Conclusion: These results suggest that GDNF delivered from encapsulated cells can augment the survival of odontoblast-like cells, and that the delivery of growth factors by encapsulated cells may be useful for enhancing pulp wound healing and regeneration. These data also pave the way for additional in vivo studies to determine the utility of this approach in regenerative endodontics.

Conjugated linolenic acids (CLN) are geometric and positional isomers of linolenic acid. Growth inhibition and apoptosis induction by alpha-eleostearic acid (c9,t11,t13-CLN), beta-eleostearic acid (t9,t11,t13-CLN), alpha-calendic acid (t8,t10,c12-CLN) and beta-calendic acid (t8,t10,t12-CLN) were compared. beta-Eleostearic acid and beta-calendic acid, which have all-trans-conjugated double bonds, exerted stronger growth inhibition and more DNA fragmentation, an indicator of apoptosis induction, in the human colon cancer cells Caco-2 than alpha-eleostearic acid and alpha-calendic acid with the cis configuration. Down-regulation of bcl-2 and up-regulation of bax mRNA by beta-eleostearic acid were also greater than by alpha-eleostearic acid. Interestingly, the cytotoxic effects of beta-eleostearic acid and beta-calendic acid were not counteracted completely by alpha-tocopherol, whereas the cytotoxic effects of alpha-eleostearic and alpha-calendic acids were lost in the presence of alpha-tocopherol. These results suggest that beta-eleostearic and beta-calendic acids have signaling pathways different from those of alpha-eleostearic and alpha-calendic acids and exhibit high potency for reducing the cell viability of Caco-2.

Streptomyces coelicolor A3(2) possesses nine genes for family 18 chitinases and two for family 19, showing high multiplicity. By hybridization analyses, distribution of those chitinase genes was investigated in six other Streptomyces species covering the whole phylogenetic range based on 16S rDNA sequences. All strains showed high-multiplicity of chitinase genes, like S. coelicolor A3(2). The phylogeny and gene organization of the family 18 chitinase genes cloned from Streptomyces species so far were then analyzed to investigate the gene evolution. It was concluded that Streptomyces already possessed a variety of chitinase genes prior to branching into many species, and that the ancestral genes of chiA and chiB have been generated by gene-duplication. In the course of the analyses, evidence that the chi30 and chi40 genes of S. thermoviolaceus were derived from their corresponding original chitinase genes by losing gene parts for substrate-binding domains and fibronectin type III-like domains was obtained. It was thus shown that gene-duplication and domain-deletion were implicated in generating the high diversity and multiplicity of chitinase genes in Streptomyces species.

To investigate the dose-response relationship and the relationships among symptoms related to the vibration syndrome, 266 chain saw operators were examined. The subjects were classified into four groups according to total operating time (TOT): Group E1 (below 2,000 hrs, n = 39), Group E2 (2,000-5,000 hrs, n = 76), Group E3 (5,000-8,000 hrs, n = 51), and Group E4 (over 8,000 hrs, n = 100). The control group (Group O) consisted of 46 healthy subjects with very brief employment period as bush cleaners. The subjective symptoms and clinical findings were divided into four major symptom categories: circulatory disturbances, sensory disturbances, damage to muscles and joints, and general symptoms such as autonomic nerve disturbances. Each major symptom category was rated from 0 to 25 according to the severity of the symptoms observed (Table 2). The mean scores in the four major symptom categories were compared for the four TOT groups in order to study the dose-response relationship. The relationship among symptoms was investigated by cluster analysis for the four major symptom categories of all operators in each group and inferred from the significance of partial correlation coefficients between the two of the four major symptom categories calculated for each group. The mean scores in the four major categories showed a significant elevation with the increase in TOT. A dose-response relationship of the vibration syndrome was proved. Each major symptom category was aggravated, not independently, but in close correlation with the symptoms. The inter-symptom relationships of the vibration syndrome were confirmed. That is, very close correlations between circulatory disturbances and sensory disturbances and between sensory disturbances and damages to muscles and joints were demonstrated.

The performance of tour Nb3Sn conductors for the ITER central solenoids was tested. The current sharing temperatures (T-cs) were measured over approximately 9000 electromagnetic cycles, including two or three thermal cycles between 4.2 K and room temperature. T-cs, increased and became almost constant through the cycling. The gradient of the electric field against the temperature gradually decreased against cycling. The degradations caused by the electromagnetic force of the short twist pitch conductors were smaller than that of the original twist pitch conductor. The ac losses of short twist pitch conductors were several times higher than that of original twist pitch conductor. The dents and the removals of the Cr plating on the strands, which were formed during cabling, decreased the electric resistance between strands, which may cause the observed high ac loss. Inspection of the cable showed neither a clear bias of cable in the cross-sectional surface nor distorted strands in the lateral face. The high rigidity of the short twist pitch cable could prevent these plastic deformations, caused by the Lorentz force.

The vitreous membrane obtained from a patient with Stickler syndrome, an 8 year-old female, was investigated electronmicroscopically. The cells found in the membrane had cilia, microvilli and cytoplasmic filaments. Gap junctions and basement membrane-like structures were also found. Several of the cells had phagosomes containing crystalline materials. Thus, these cells seemed to be glial cells.