Unique three-way translocation, t(3;14;18)(q27;q32;q21), in follicular lymphoma

A 43-year-old woman was diagnosed as having stage IV follicular lymphoma. Phenotypically, the lymphoma cells were CD5(-), CD10(+), CD19(+), CD20(+), CD23(-), HLA-DR(+), and IgM-lambda(+). Conventional chromosomal analysis showed a three-way t(3;14;18)(q27;q32;q21) in the lymphoma cells, which was confirmed by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Immunohistochemistry revealed that both BCL2 and BCL6 proteins were expressed in the lymphoma cells, whereas only the BCL6 gene, and not the BCL2 gene, was rearranged by Southern blotting. The patient received combination chemotherapy and has been well for 3 years. This is the first reported case showing a three-way translocation involving 2 major lymphoma-specific abnormalities, 3q27 and t(14;18)(q32;q21).     

Why is the diverse U letter relationship between embarrassment and psychological distance observed? In view of Schlenker and Leary (1982)'s self-presentation model of social anxiety

The aim of the present study is to explain why there is "the diverse U letter relationship" between embarrassment and psychological distance empirically, in view of Schlenker and Leary (1982)'s self-presentation model of social anxiety. In Study 1, those relationships were observed in three different situations. In Study 2, the main effect of motivation for avoiding rejection and the damage of self-image, and their interaction with embarrassment was examined by hierarchical regression analysis. In the first step, the psychological distance, in the second step, the main effect of both, and in the third step, the interaction was entered. As a result, in the second step, both main effects were significant, but in the third step, only interaction was significant, and both main effects were not significant. This showed that the interaction could predict embarrassment, although the psychological distance was controlled. Finally, this result was discussed in view of social norm.     

Proapoptotic effect of proteolytic activation of matrix metalloproteinases by Streptococcus pyogenes thiol proteinase (Streptococcus pyrogenic exotoxin B)

Streptococcus pyogenes thiol proteinase, also known as streptococcal pyrogenic exotoxin B (SpeB), has been suggested to be a major virulence factor in S. pyogenes infection. SpeB was reported to induce apoptosis of host cells, but its mechanism of action is not yet fully understood. In this study, we examined the involvement of matrix metalloproteinases (MMPs) in SpeB-induced apoptosis. We first developed a large-scale preparation of recombinant SpeB and precursors of human MMP-9 and -2 (proMMPs) by using Escherichia coli Rosetta (DE3)pLysS and baculovirus-insect cell expression systems, respectively. Treatment with SpeB induced effective proteolytic activation of both proMMP-9 and -2. When RAW264 murine macrophages were incubated with SpeB-activated proMMP-9, the level of tumor necrosis factor alpha (TNF-alpha) in conditioned medium (CM), assessed by an enzyme immunoassay, was elevated. This increase was completely inhibited by addition of the MMP inhibitor SI-27 to the cell culture. The CM also produced marked induction of apoptosis of U937 human monocytic cells. Similarly, soluble Fas ligand (sFasL) was detected in CM of cultures of SW480 cells expressing FasL after treatment with SpeB-activated proMMPs; this CM also induced apoptosis in U937 cells. SpeB had a direct effect as well and caused the release of TNF-alpha and sFasL from the cells. SpeB-dependent production of MMP-9 and -2 and proapoptotic molecules (TNF-alpha and sFasL) was evident in a murine model of severe invasive S. pyogenes infection. These results suggest that SpeB or SpeB-activated MMPs contribute to tissue damage and streptococcal invasion in the host via extracellular release of TNF-alpha and sFasL.     

Mechanisms responsible for delayed and immediate hemolytic transfusion reactions in a patient with anti-E + Jk(b)+ Di(b) and anti-HLA alloantibodies

Immediate hemolytic transfusion reactions (IHTR) occurred in the course of delayed hemolytic transfusion reactions (DHTR). An 84-year-old man had received a blood transfusion 20 years ago. Progressive anemia developed, because of continuous bleeding from a bladder tumor. He was transfused with concentrated red blood cells (CRC) which were Rh-E antigen negative, because he had anti-E antibodies (day 0). He received CRC on day 3, and underwent resection of bladder tumor on day 6. Although crossmatch-compatible CRCs were prepared for the operation, those were not required and were kept in a refrigerator in the ward. On day 9, when a CRC kept in the ward was transfused, he suddenly had a IHTR. In order to analyze a mechanism of IHTR, the anti-Jk(b) and anti-Di(b) antibodies, anti-HLA antibodies and the concentrations of inflammatory cytokines were measured in serum samples. The anti-Jk(b) and anti-Di(b) antibodies increased prior to IHTR experienced on day 9. The concentrations of IL-6 and IL-1beta increased from day 2, while the concentration of IL-8 increased from day 7. The anti-HLA class I antibody could be detected 2 days before IHTR. Thus, the anti-Jk(b) and anti-Di(b) antibodies induced the production of inflammatory cytokines and symptoms of DHTR and IHTR. The anti-HLA class I antibody could be produced in spite of using the filer for removing leukocytes, and may take part in the induction of IHTR. Further, blood products should be transfused soon after completing a crossmatch test in patients with anti-RBC alloantibodies.     

The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization

Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.     

Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan

CD56 is an important marker for prospecting clinicopathologic features of cytotoxic T-cell and natural killer (NK)/T-cell lymphomas. We examined 22 cases of subcutaneous panniculitis-like lymphoma and classified these into CD56-positive and CD56-negative groups. The 11 CD56-negative cases were mainly in the younger age group and had systemic subcutaneous nodules without ulceration. They exhibited subcutaneous invasion by medium-sized lymphoma cells, scattered erythrophagocytosis, patchy necrosis, and little tumor invasion in the superficial dermis. Their lymphoma cells had characteristics of CD3 epsilon-, CD8-, TcR beta F1-, T-cell intracellular antigen (TIA)1-, and granenzyme B-positive cytotoxic T cells and were negative for apoptosis-promoting proteins CD95 (Fas), Bax, CPP32 (caspase 3), and p53 (DO7). Ten patients were alive despite clinical signs of hemophagocytic syndrome and relapses in 7 cases. The 11 CD56-positive cases had systemic ulcerative skin tumors composed of pleomorphic lymphoma cells with massive necrosis and little erythrophagocytosis involving the subcutis and also often the whole dermis. Their tumor cells were positive for CD3 epsilon, TIA1, granenzyme B, CD95, CD95L (Fas ligand), Bax, and CPP32. Three cases were of the TcR beta F1-positive phenotype, 1 was of the TcR gamma/delta-positive T-cell phenotype, and 6 were of the TcR beta F1- and TcR gamma/delta-negative NK/T-cell phenotype. Six cases were p53 (DO7) positive. Seven cases had complications of liver dysfunction and cytopenia, and 8 died of disease. One CD56-negative case and 3 CD56-positive cases had nuclear signals of Epstein-Barr virus-encoded RNA in their lymphoma cells. The 2 groups had significantly (P <0.01) different prognoses by Kaplan-Meier and log-rank methods. Patients with CD56-negative and CD56-positive groups had statistically different clinicopathologic, immunohistologic, and functional findings and prognoses.     

The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen

Hepatitis B surface antigen possesses the group-specific determinant called a and one or another member from each of two pairs of allelic determinants, d and y as well as w and r, thereby creating the four major subtypes, adw, adr, ayw and ayr. In the sequence of major surface antigen polypeptides made of 226 amino acid residues, lysine or arginine at amino acid position 122 specifies d or y determinant, and lysine or arginine at position 160 specifies w or r determinant, respectively. By means of site-directed mutagenesis and expression of mutant genes in cultured cells, the mechanism for the loss of subtypic determinants on surface antigens was investigated at the molecular level. A rare sample of surface antigen of subtype ad, devoid of w or r determinant, had asparagine at position 160. When it was converted to lysine, the surface antigen of subtype adw was obtained. Two samples of surface antigen were subtyped as ar. They lacked d determinant, despite having lysine at position 122 which usually specified it. They differed from all reported sequences of surface antigen in amino acid 144 or 145. They displayed d determinant when amino acid 144 was converted from glutamic acid to aspartic acid, or when amino acid 145 was changed from alanine to glycine. These results indicate that the key amino acid residue at position 122 or 160 is indispensable for the expression of subtypic determinants and that some distant residues are also crucially involved in conforming them.     

Evidence that action potential generation is not the exclusive determinant to trigger spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle

Urinary bladder smooth muscle (UBSM) exhibits spontaneous contraction. This spontaneous mechanical activity is myogenic and can be closely related to the UBSM cell action potential to facilitate Ca2+ influx through voltage-gated Ca2+ channels. In the present study, to know whether this membrane electrical event is the exclusive mechanism to trigger spontaneous smooth muscle contraction, we compared the inhibitory effects of Ca2+ channel blockers on the spontaneous action potential and mechanical activity in the isolated guinea-pig UBSM. Both action potential and rhythmic contraction were generated spontaneously in the presence of atropine (1 microM), phentolamine (1 microM), propranolol (1 microM), suramin (10 microM) and tetrodotoxin (1 microM), which suggest that both phenomena were myogenic in origin. Nisoldipine (100 nM) and diltiazem (10 microM) completely eliminated the generation of action potential whereas its frequency was dramatically increased by a dihydropyridine Ca2+ agonist, BayK 8644 (1 microM). In contrast to disappearance of action potential in the presence of Ca2+ channel blockers, spontaneous contraction of UBSM was inhibited only partly by nisoldipine or diltiazem and most of the mechanical components persisted in these channel blockers. These results indicate that spontaneous action potential in UBSM cell is generated through the activation of L-type voltage-gated Ca2+ channels. The subsequent elevation of intracellular Ca2+ concentrations during a burst of action potentials can be partly responsible for the induction of UBSM mechanical activity. In addition, the present study provides evidence that UBSM spontaneous mechanical activity is also attributable to the mechanism(s) other than the generation of Ca2+ spike.     

The levels of cerebrospinal fluid Abeta40 and Abeta42(43) are regulated age-dependently

Decreased levels of cerebrospinal fluid (CSF) Abeta42 is a diagnostic marker of Alzheimer's disease. To clarify the biological basis of this marker, the physiological alterations of CSF Abeta40 and Abeta42 by aging were studied. CSF samples from 92 normal subjects between 8 and 89 years old were measured using a specific ELISA for Abeta40 and Abeta42(43). High concentrations of Abeta40 and Abeta42(43) in the young group, under 29 years old, changed to be at low concentrations in the adult group between 30 and 59 years old. Subsequently, the levels increased again with age. Third order regression analysis showed a significant correlation between the levels of Abeta40 and age (Y = - 169 X(3) + 3.1X(2)- 0.02X + 4135; P < 0.034) and between the levels of Abeta42(43) and age (Y = - 46 X(3) + 0.9 X(2)- 0.005X + 992; P < 0.005). The levels of CSF Abeta40 and Abeta42(43) were physiologically regulated to show a U-shaped natural course in normal aging. These findings suggested that the physiological increase of Abeta42(43) over 59 years of age is selectively inhibited in Alzheimer's disease.