A peculiar case of precursor B lymphoblastic leukaemia/lymphoma histologically mimicking diffuse large B-cell lymphoma.
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Aged↗
Biomedical subjects
K Tasaki
Publications and source records attributed to K Tasaki.
Interleukin-17 stimulates chemokine (interleukin-8 and monocyte chemoattractant protein-1) secretion in human pancreatic periacinar myofibroblasts.
BACKGROUND: Interleukin (IL)-17 is a newly identified T-cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion in human pancreatic periacinar myofibroblasts. METHODS: The secretion of IL-8 and monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). RESULTS: IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression. Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity, and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding activity. CONCLUSIONS: In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The combination of IL-17 with IFN-gamma further enhances chemokine secretion. These findings indicate a linkage between T-cell-mediated immunity and inflammatory responses in the pancreas.
Blotting, Northern↗
A case of toxic shock-like syndrome presenting with serious hypoproteinaemia because of a protein-losing gastroenteropathy.
A 37-year-old man was admitted to our hospital because of toxic shock-like syndrome (TSLS) induced by Streptococcus pyogenes. After the pathogenic bacteria had been eradicated, serious diarrhoea appeared and a protein-losing gastroenteropathy developed. An immunohistochemical study of the biopsy specimens of both small and large intestines revealed the infiltration of T-lymphocytes, predominantly CD8+ cells, into the lamina propria of affected mucosa, villus atrophy and crypt hyperplasia. Considering these histological findings, some immunological mechanism which lead the activation of cytotoxic T-lymphocytes may play an important role in the pathogenesis of this rare intestinal manifestation of TSLS.
Adult↗
Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells.
We investigated the antitumor effects induced by the production of interleukin-12 (IL-12) or IL-18, which influence the function of T helper type 1 cells, in murine colon carcinoma cells (Colon 26). Retrovirally transduced cells with IL-12 genes that encoded both p35 and p40 (Colon 26/IL-12) lost their tumorigenicity when inoculated subcutaneously or intraperitoneally into syngeneic immunocompetent mice. Moreover, the mice that had rejected the Colon 26/IL-12 cells generated protective immunity to wild-type (wt) cells when subsequently challenged. Colon 26 cells transduced with the IL-18 gene (Colon 26/IL-18) could not form subcutaneous tumors in immunocompetent mice, and the mice became resistant to inoculated wt cells. Immunohistochemical analysis revealed that the numbers of blood vessels in Colon 26/IL-12 or Colon 26/IL-18 tumors were markedly reduced, and that the expression of adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 increased on the endothelium in the stroma of Colon 26/IL-12 tumors. The loss of tumorigenicity of Colon 26/IL-12 or Colon 26/IL-18 cells was not observed in immunocompromised mice. However, the survival days of the immunocompromised mice inoculated with Colon 26/IL-12 but not Colon 26/IL-18 cells were significantly longer than those inoculated with wt cells. The secretion of cytokines that stimulate T helper type 1 cells from tumor cells can thereby induce an antitumor response. However, the effector cells involved in these antitumor effects could differentially migrate to the tumors, and the inhibition of angiogenesis may partially contribute to the antitumor responses observed.
Animals↗
Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts.
We examined the antitumor effects caused by murine colon carcinoma cells (Colon 26) transduced with interleukin-15 (IL-15) gene. Although the in vitro proliferation rate of IL-15-secreting Colon 26 (Colon 26/IL-15) cells was not different from that of wild-type (wt) cells, small subcutaneous tumors of Colon 26/IL-15 cells that developed in syngeneic immunocompetent mice regressed spontaneously in contrast to tumors of wt cells. The mice that had eliminated tumors of Colon 26/IL-15 cells rejected wt cells when subsequently challenged. The survival of the mice that had been inoculated intraperitoneally with Colon 26/IL-15 cells was significantly prolonged compared with that of the mice injected with wt cells. However, in an experimental lung metastasis model, the survival of the mice inoculated with Colon 26/IL-15 cells remained the same as that of the mice inoculated with wt cells. The inoculation of Colon 26/IL-15 cells into immunocompromised nude or severe combined immunodeficient mice produced tumors, but the survival of the immunocompromised mice was significantly longer than that of the mice inoculated with wt cells. The nude mice inoculated with Colon 26/IL-15 cells also survived longer than the severe combined immunodeficient mice with Colon 26/IL-15 cells. Depletion of natural killer cells in nude mice with anti-asialo GM1 antibody did not influence the survival of the mice injected with Colon 26/IL-15 cells. Immunohistological examination revealed that CD31+ cells migrated into tumors of Colon 26/IL-15 cells that developed in immunocompetent and immunocompromised mice. Taken together, our results indicate that an inoculation of IL-15-producing tumor cells can produce antitumor effects that are mediated by a variety of immunocompetent cells.
Animals↗
Impaired tumorigenicity of human pancreatic cancer cells retrovirally transduced with interleukin-12 or interleukin-15 gene.
We examined the antitumor effect of locally secreted interleukin (IL)-12 or IL-15 on human pancreatic cancer cells (AsPC-1). We subcutaneously inoculated AsPC-1 cells retrovirally transduced with IL-12 or IL-15 cDNA into nude mice. Tumors derived from these cells showed retarded growth compared with those from wild-type (wt) cells. Nude mice inoculated intraperitoneally with the cytokine producers survived longer than those injected with wt cells. These cytokine producers were also tested for their tumor growth in severe combined immunodeficient mice. The tumor growth of IL-12 producers was similarly suppressed as found in nude mice, but the average tumor volumes of IL-15 producers were not statistically different from those of wt tumors. In nude mice that were administered anti-asialo GM1 antibody before the inoculation of the tumor cells, growth retardation of tumors of IL-12 producers remained the same as in untreated animals, but that of IL-15 producers was markedly reduced. Immunohistochemical analysis revealed that CD11b+ cells migrated into the tumors of cytokine producers and that the number of CD31+ endothelial cells within the tumors was not different between IL-12 producers and wt cells. Taken together with other data, it is possible that granulocytes are candidate cells for the IL-12-mediated antitumor effect, and that natural killer cells and gammadelta T cells are involved in the IL-15-induced antitumor effect. We did not observe synergistic effects of these cytokines to suppress subcutaneous tumors.
Animals↗
Expression of Escherichia coli uracil phosphoribosyltransferase gene in murine colon carcinoma cells augments the antitumoral effect of 5-fluorouracil and induces protective immunity.
Uracil phosphoribosyltransferase (UPRT) of Escherichia coli origin can convert 5-fluorouracil (5-FU), a chemotherapeutic agent widely used for solid tumors, to an active intermediate, 5-fluorouridine-5'-monophosphate, as mammalian orotate phosphoribosyltransferase does. To examine whether the E. coli UPRT gene expressed in tumor cells can confer increased sensitivity to 5-FU, we retrovirally transduced Colon 26 cells, a murine colon carcinoma cell line, with the UPRT gene (Colon 26/UPRT cells) and tested the in vivo antitumoral effect of 5-FU in syngeneic immunocompetent mice. After 5-FU administration, tumors of Colon 26/UPRT cells regressed, whereas those of wild-type cells were unaffected. The mice that once eliminated Colon 26/UPRT tumors after 5-FU treatment rejected wild-type cells that were subsequently inoculated but not irrelevant syngeneic tumor cells. This suicide gene/prodrug system was less efficient in nude mice, suggesting that mature alphabeta T cells play a role in the antitumoral effect. The cytotoxicity mediated by the bystander effect was marginal in this system, contrary to the herpes simplex virus-thymidine kinase gene/ganciclovir system. Therefore, expression of the UPRT gene in tumor cells followed by 5-FU administration is a possible strategy for cancer gene therapy, but potentiation of the bystander effect is required for its therapeutic application.
Adenocarcinoma↗
Immunological responsiveness to interleukin-2-producing brain tumors can be restored by concurrent subcutaneous transplantation of the same tumors.
The central nervous system shows tolerance for activated host immune reactions, and this relative unresponsiveness may lessen the efficacy of an immunotherapy for brain tumors. Using interleukin-2 (IL-2)-producing 9L rat gliosarcoma cells (9L/IL-2), we examined whether secretion of IL-2 from subcutaneous (s.c.) and/or intracerebral (i.c.) tumors can elicit augmented immunological responses to brain tumors. Syngeneic rats could reject 9L/IL-2 cells inoculated s.c., but developed 9L/IL-2 brain tumors by i.c. inoculation. The growth of i.c. 9L/IL-2 tumors was, however, significantly retarded compared with that of i.c. wild-type tumors. The growth of i.c. wild-type tumors was significantly suppressed when the rats concurrently received 9L/IL-2 cells s.c. Moreover, most of the rats that were inoculated i.c. with 9L/IL-2 cells did not develop brain tumors when concurrently injected s.c. with 9L/IL-2 cells. Immunohistochemical analysis on i.c. 9L/IL-2 tumors, when the rats were concurrently inoculated s.c. with 9L/IL-2 cells, revealed that migration of CD4+ or CD8+ T cells, monocytes/microglias, and macrophages was markedly augmented to a similar level as found in the s.c. 9L/IL-2 tumors. These results showed that systemic immune responses to brain tumor were induced in an immunologically privileged site by concurrent s.c. inoculation of the same tumors that produce IL-2. The present study may also raise the possibility of a therapeutic strategy for brain tumors by the combinatory expression of IL-2 gene using s.c. immunization followed by direct gene transfer into brain tumors.
Animals↗
Dietary patterns are associated with body mass index in multiethnic women.
This cross-sectional study investigated the relationship between dietary patterns and body mass index among 514 women with different ethnic backgrounds who completed a validated food-frequency questionnaire. An exploratory factor analysis with orthogonal rotation started with 23 food items and resulted in four factors that accounted for 93% of the total variance. Confirmatory factor analysis with the 16 items that had factor loadings of at least 0.60 validated the four dietary patterns. The most significant dietary pattern, "meat," was characterized by high intake of processed and red meats, fish, poultry, eggs, fats and oils, and condiments. The "vegetable" pattern loaded high on different vegetables, whereas the third pattern named "bean" was high in legumes, tofu and soy protein. The major components of the "cold foods" pattern were fruit, fruit juice and cold breakfast cereals. Although the "meat" pattern was predominant among Hawaiians and the "bean" pattern very common among Chinese and Japanese women, factors two and four were not related to ethnicity. After adjustment for daily energy intake, the "meat" pattern was positively associated with body mass index (r = 0.17, P: = 0.0001), whereas the other three patterns showed negative relationships to body mass index (r = -0.076, P: = 0.084, r = -0.13, P: = 0.003, and r = -0.13, P: = 0.003) for vegetables, beans and cold foods, respectively. The associations were similar in direction and magnitude for all ethnic groups. The study results support the ideas that choosing the right foods may be important in weight control and that food-based dietary patterns may be useful in dietary counseling.
Adult↗
[X-ray and endoscopic diagnosis of esophageal achalasia].
We evaluated diagnostic X-ray and endoscopic examination findings in 486 patients with esophageal achalasia. Concerning the association between the duration of disease and the X-ray dilatation type, the duration was 1-4 years in more than 50% of patients with the Sp type, a mean of 8.5 years in those with the F type, and frequently more than 10 years in those with the S type. Endoscopy is generally used to determine the presence or absence of abnormal movement. In achalasia, the endoscope can be inserted into the stomach despite resistance at the stenotic site, and the mucosal surface is normal. Squamous cell carcinoma as a complication was observed in 21 patients (4.3%). The carcinoma complication rate was higher with a longer duration of disease and a longer observation period. The mean total course including the postoperative course was 27 years. Long-term and periodic X-ray and endoscopic observation of the disease course is important, and iodine staining is indispensable for early detection of esophageal cancer.
Adolescent↗
Differential modulation of nitric oxide and prostacyclin release in senescent rat heart stimulated by angiotensin II.
To elucidate the mechanism of age-related changes in the cardiovascular function stimulated with angiotensin II, we examined the effects of angiotensin II on the coronary flow, production of nitric oxide (NO) and prostacyclin, and on the cardiac function in the Langendorff-perfused young and aged rats' hearts. Angiotensin II decreased coronary flow, left ventricular dP/dt and heart rate. These effects were more pronounced in aged rats. Pretreatment with a NO synthase inhibitor, N(G)-nitro-L-arginine, significantly increased the angiotensin II-induced vasoconstriction in young rats. Angiotensin II increased the concentration of NO in the coronary effluent in young but not in aged rats. In contrast, angiotensin II stimulated the release of prostacyclin to a much greater extent in aged rats than in young rats. These results suggest that impaired production of NO may contribute to the greater constrictor effect of angiotensin II in the aged rat, although aging modulated the production of prostacyclin in a different manner. This age-related endothelial dysfunction may alter the physiological regulation of coronary flow and cardiac function stimulated with angiotensin II.
Acetylcholine↗
Analysis of the immunoglobulin heavy chain gene variable region of 101 cases with peripheral B cell neoplasms and B cell chronic lymphocytic leukemia in the japanese population.
We have analyzed the immunoglobulin heavy chain (VH) gene variable regions (CDR2 and FW3) of 101 Japanese cases with peripheral B cell neoplasms. When all except one case with a deletion were graphed by frequency of replacement mutation, the 100 cases could be separated into two groups: 24 cases with zero, one and two mutations (germline or low frequency of somatic mutation); and 76 cases with three or more mutations (medium to high frequency of somatic mutation). While most mantle cell lymphoma cases (11/13) showed germline or low frequency of somatic mutation, all cases of mucosa-associated lymphoid tissue (MALT) lymphoma (11/11), follicular lymphoma (three of three cases), plasma cell myeloma (seven of seven cases) and most cases of diffuse large B cell lymphoma (DLBCL; 42/47) belonged to the latter group. These 76 cases, therefore, may be considered to show somatic hypermutation. More than half of chronic lymphocytic leukemia/small lymphocytic lymphoma cases (CLL/SLL; eight of 13) showed a hypermutated VH gene and the ratio of replacement mutation: silent mutation in CDR2 of CLL/SLL was considerably higher compared with DLBCL and MALT lymphoma, showing somatic hypermutation. When comparing VH gene type of B cell-CLL (B-CLL) among our series and those in the literature, more cases of CD5+ B-CLL in the Western literature have the VH5 and VH6 family types, while more cases in Japan are reported to have VH4 family. The occurrence of VH families in B-CLL between Japanese and Western people seems to be comparable.
Aged↗
[Suppression of stress proteins in endoplasmic reticulum in liver cytosol of rats treated with a highly toxic coplanar PCB].
The present study was addressed on the effect of 3,3',4,4',5-pentachlorobiphenyl (PenCB) to the expression of glucose regulated protein (GRP) 78 and GRP94 in liver endoplasmic reticulum of rat by treatment with the schedule after acute or subacute exposure. In the acute exposure, male Wistar rats received PenCB in corn oil at once a dose of 25 mg/kg i.p., then at 5 days after treatment the microsomes were prepared. Free- and pair-fed control groups were given the vehicle. The microsomal proteins were separated on SDS-PAGE, transferred to membrane and blotted using anti-sera to the GRPs. The reduction of GRP78 and GRP94 was associated significantly with the acute exposure. In subacute exposure, the rats received PenCB in corn oil at once a dose of 0.1 or 1.0 mg/kg i.p. At 4 weeks after treatment, liver microsomes were obtained. The expression level of GRP78 and GRP94 are also decreased at 1.0 mg PenCB/kg treatment as similar as the acute exposure. But the reduction was not notable at 0.1 mg PenCB/kg treatment. GRP78 and GRP94 are a member of GRPs and the expression is regulated by glucose in cells as stress proteins. GRP78 and GRP94 have also the function for chaperone protein. Chaperone proteins have important physiological functions against synthesized and/or denatured proteins, which include assembling, folding of proteins. Our results suggested that a part of the toxicity of PenCB is associated to significant decrease of the chaperone proteins in the endoplasmic reticulum.
Animals↗
[Induction of molecular chaperones HSP70 and HSP90 in rat liver cytosol by a highly toxic coplanar PCB].
We report here that a highly toxic coplanar polychlorinated biphenyl (PCB), 3,3',4,4',5-pentachlorobiphenyl (PenCB) induces molecular chaperones, HSP70 and HSP90 in liver cytosol of rats. Male Wistar rats received PenCB in corn oil once at a dose of 25 mg/kg i.p. Pair-fed control groups were treated with the vehicle and given the amount of chow matched with that taken by the PenCB-treated animals, and free-fed controls were given the vehicle. The liver cytosolic HSP70 level in rats treated with PenCB was 5-fold higher than those in free-fed controls, though that for pair-fed controls was approximately 2-fold higher than that in free-fed controls. The liver cytosolic HSP90 alpha and HSP90 beta levels were also higher in PenCB-treated rats than in both control groups, but the induction extent was lesser than that for HSP70. Inductive effect on the chaperones was examined with a single different dose of PenCB 0, 0.5, 1.0, 5.0, 10 and 25 mg/kg. Marked induction of the HSP70 level was observed with a minimum dose of PenCB 0.5 mg/kg. The HSP90 alpha level was induced with PenCB-dose dependent manner although the HSP90 beta induction was greatest with a dose of PenCB 5.0 mg/kg. HSP70 and HSP90 are essential for cells under normal conditions and act as molecular chaperones. HSP90 is well known to modulate the function of sex steroid hormone or aromatic hydrocarbon receptors while HSP70 is required for receptor-HSP90 heterocomplex assembly. The role of molecular chaperones may be involved in the endocrine disrupting properties of coplanar PCB and dioxins.
Animals↗
Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive diffuse large B-cell lymphoma.
To clarify the cell origin of CD5+ diffuse large B-cell lymphoma (DLBCL), we analyzed and compared the variable region of the immunoglobulin heavy chain gene (VH gene) in eight cases of CD5+ DLBCL and 23 cases of other CD5+ B-cell neoplasms; 10 cases of chronic lymphocytic leukemia (CLL), one case of small lymphocytic lymphoma, one case of hairy cell leukemia, and 11 cases of mantle cell lymphoma. CD5+ DLBCL were comprised of two cases of de novo lymphoma of nodal origin, five cases of de novo lymphoma of extranodal origin, and one case of Richter transformation. Whereas all cases of mantle cell lymphoma except one showed a germ line or low mutation frequency of the rearranged VH gene, the rearranged VH genes in both CD5+ CLL and CD5+ DLBCL were heterogeneous. The degree of somatic mutation of CD5+ CLL and CD5+ DLBCL ranged between approximately 0 to 15.0% and 0.7 to 12.9%, respectively. High frequency of expression of the VH4 family in both CD5+ CLL and CD5+ DLBCL was found. Moreover, none of the three cases of CD5+ DLBCL examined exhibited intraclonal diversity. These findings may be common characteristics of the rearranged VH gene of CD5+ CLL and CD5+ DLBCL and suggested that the cell origin of CD5+ DLBCL was the same as that of CD5+ CLL.
Aged↗
Peripheral T-cell lymphoma other than angioimmunoblastic T-cell lymphoma (AILD), with follicular dendritic cells proliferation and infection of B immunoblasts with Epstein Barr virus.
We describe a case of peripheral T-cell lymphoma, unspecified (REAL) with co-existence of follicular dendritic cell (FDC) proliferation and EB virus-infection. A 55-year-old Japanese man complained of generalized lymphadenopathy and physical examination showed systemic lymphadenopathy, and hepatosplenomegaly. HTLV-1 antibody titers and gamma-globulin level were within normal limits. Histopathologic examination of the right cervical lymph node showed peripheral T-cell lymphoma, unspecified (REAL classification). A diffuse infiltration of lymphoma cells with abundant small venules were found throughout the lymph node. There were few arborizing venules. An irregular meshwork of FDCs was found by immunostaining with DRC-1 and CD21 in the area rich in venules, but not in the area of diffuse lymphoma cell-infiltration. EBER-1 RNA-in situ hybridization showed positive signal on the nuclei of mainly non-neoplastic B immunoblasts. The present case, therefore, was regarded as a rare case of peripheral T-cell lymphoma, unspecified with FDC proliferation and EB virus infection.
B-Lymphocytes↗
Nodal marginal zone B-cell lymphoma with peculiar follicular colonization involved by malignant lymphoma of thyroid gland.
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Aged↗
Closed form of liganded glutamine-binding protein by rotational-echo double-resonance NMR.
Rotational-echo double-resonance NMR has been used to determine internuclear distances in the complex of glutamine-binding protein and its ligand, l-glutamine. The distances between the ligand and Tyr185 are consistent with the results of molecular dynamics simulations constrained by three REDOR-determined distances to His156. This model is also consistent with six other REDOR-determined internuclear distances, most of which agree with values from the first report of an X-ray structure of the complex of glutamine-binding protein and l-glutamine.
Carrier Proteins↗