High-grade mature B-cell lymphoma with Burkitt-like morphology: results of a clinicopathological study of 72 Japanese patients

The aim of the present study was to estimate optimum chemotherapeutic regimens for high-grade mature B-cell lymphoma cases with Burkitt-like morphology (Burkitt's lymphoma [BL]/Burkitt-like lymphoma [BLL]) patients. We analyzed 72 BL/BLL, including 36 with the c-myc translocation (molecular BL [mBL]), 20 without it (mBL-like), and 16 in whom we were uncertain regarding the existence of the c-myc translocation, and compared them with 182 diffuse large B-cell lymphoma (DLBCL) cases. On clinical and immunophenotypic analysis, the typical BL immunophenotype (CD10 positive, bcl-2 negative, and Ki-67 index ≥95%) was noted in 23 (66%) and 11 (55%) of the 35 mBL and 20 mBL-like patients, respectively. The presence of the c-myc translocation and typical immunophenotype in BL did not affect the overall survival of BL/BLL. There were no significant differences between the overall survival of DLBCL (45%) and BL/BLL (50%, P =  0.85). However, the overall survival of BL/BLL patients who received cyclophosphamide, doxorubicin, vincristine, and prednisolone-related therapy (22%) was significantly lower than that of DLBCL patients ( P =  0.01). In contrast, the overall survival of BL/BLL patients who received aggressive short-term chemotherapy (75%) was better than that of the patients who received cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy ( P <  0.01). The finding was confirmed by multivariate analysis (hazard ratio 4.4; confidence interval 2.0–9.7; P  = 0.0003). We concluded that aggressive short-term chemotherapy improves survival in BL/BLL, regardless of its genetic and immunophenotypic features. ( Cancer Sci 2008; 99: 246–252)     

Human herpes virus 8-negative primary effusion lymphoma (PEL) in a patient after repeated chylous ascites and chylothorax

We describe a case of malignant lymphoma which presented in the body cavities without identifiable tumor masses. Malignant lymphoma cells showed strong atypia with prominent nuclei and basophilic cytoplasm containing vacuoles. The chromosomes showed diploidy and complex abnormalities including translocations and deletions. We diagnosed this patient with primary effusion lymphoma (PEL), even though she tested negative for human herpes virus-8 (HHV-8) which has been suggested to be causally related to PEL. Interestingly, the patient also showed complicated protein-losing enteropathy, and PEL occurred after repeated chylous ascites and chylothorax. The possible pathogenesis of this rare disease is discussed here.     

NKG2D defines tumor-reacting effector CD8+ T cells within tumor microenvironment

For successful immunotherapy for cancer, it is important to understand the immunological status of tumor antigen-specific CD8⁺ T cells in the tumor microenvironment during tumor progression. In this study, we monitored the behavior of B16OVA-Luc cells in mice immunized with a model tumor antigen ovalbumin (OVA). Using bioluminescence imaging, we identified the time series of OVA-specific CD8⁺ T-cell responses during tumor progression: initial progression, immune control, and the escape phase. As a result of analyzing the status of tumor antigen-specific CD8⁺ cells in those 3 different phases, we found that the expression of NKG2D defines tumor-reacting effector CD8⁺ T cells. NKG2D may control the fate and TOX expression of tumor-reacting CD8⁺ T cells, considering that NKG2D blockade in OVA-vaccinated mice delayed the growth of the B16OVA-Luc2 tumor and increased the presence of tumor-infiltrating OVA-specific CD8⁺ T cells.     

Dysregulation of IL-13 production by cord blood CD4+ T cells is associated with the subsequent development of atopic disease in infants.

Early intervention strategies in allergic diseases will be dependent on identification of newborns at high risk for later development of atopic disease. In this cohort study of 106 neonates, we investigated whether cytokine production property and responsiveness to IL-12 of neonatal CD4(+) T cells were associated with the subsequent development of atopic disease and whether a skewed cytokine production property was intrinsic to helper T cells. To exclude the effects of contaminating cells, highly purified cord blood CD4(+) T cells were stimulated with anti-CD3 MAb and recombinant B7-2 molecule in the presence or absence of IL-12. Production of IL-13 and interferon-gamma was determined by ELISA. The infants were assessed at 12 mo for the development of atopic diseases. CD4(+) T cells of neonates who manifested allergic symptoms (atopic group) produced higher levels of IL-13 compared with those of the nonatopic group in both the presence and absence of IL-12. No significant difference was noted between the two groups with respect to interferon-gamma production. Moreover, higher IL-13 production was also observed in neonates with chronic eczema than those with short-term eczema. Our data suggest that increased production of IL-13 by neonatal CD4(+) T cells is a useful marker of newborns at high risk for subsequent development of atopic diseases and that an intrinsic abnormality of CD4(+) T cell is associated with the pathogeneses of atopic disease, especially atopic dermatitis in infants.     

Antimicrobial resistance of Staphylococcus aureus isolated from impetigo patients between 1994 and 2000

BACKGROUND: The incidence of strains of Staphylococcus aureus resistant to the antimicrobial agents used in treating impetigo has been increasing. AIM: To determine the antimicrobial susceptibility of S. aureus in impetigo. METHODS: We measured the antimicrobial susceptibility of Staphylococcus aureus isolated from impetigo patients between 1994 and 2000. RESULTS: The MIC50 of gentamicin was always higher than that of other antimicrobial agents until 1999. In isolates obtained since 1996, the MIC90 of gentamicin was over 12.5 micro g/mL, which is markedly higher than that found for other skin infections (folliculitis, furuncles, paronychia, phlegmone, secondary infection of eczema, dermatitis, ulcer and decubitus). There were no strains of S. aureus resistant to vancomycin and fusidic acid. After 2000, we could find only one strain resistant to minocycline and ofloxacin. CONCLUSION: Clindamycin has shown excellent activity against most S. aureus isolates between 1994 and 2000. The incidence of methicillin-resistant S. aureus was always below 20%.     

Treatment resistant chronic psychopathology and CT scans in schizophrenia

In order to examine the relationship between the neuroleptic resistant chronic psychopathology and CT findings in schizophrenia, 25 schizophrenics who had been treated well and were in a stable condition were assessed for positive and negative symptoms, CT findings, medication, and the clinical course of illness. Correlational analysis showed that there was a group of patients who had comparatively small ventricles and presented treatment resistant positive symptoms, and another group of patients who had larger ventricles and lacked positive symptoms. Negative symptoms showed a tendency toward positive correlation with atrophic CT changes of cortices. Literature on CT findings and symptomatology was critically reviewed. The importance of the more chronic positive symptoms correlating to CT findings in schizophrenia were discussed.     

Clinical studies on endocrine therapy for prostatic carcinoma (5): Analyses of relapse from endocrine therapy]

Prostate carcinomas are well known to be initially responsive to endocrine therapy. However, a significant number of the patients experience a relapse from endocrine therapy during the follow-up period. We clinically analyzed various aspects of the relapse which indicate a limitation in the effectiveness of endocrine therapy for prostate carcinoma. In a total of 372 patients, 117 (31.5%) had some evidence of local relapse such as regrowth of the primary lesion, or a generalized relapse such as re-elevation of total acid phosphatase, reactivation of previously present metastasis or the new appearance of metastasis, during endocrine therapy. Of these, one-fourth had local relapse alone and the remainder showed generalized relapse. The interval from the start of the treatment to the time of relapse tended to become shorter; 45.9 months (mean) in stage B, 36.8 in stage C and 29.3 in stage D, according to the stage progression. As to the non-relapse rate of the primary lesion, no differences were found among the stage, with the rate being approximately 90% at the fifth year in each stage. However, the generalized relapse-rate tended to increase with the stage progression. In the generalized relapse, the patients of stage C or D showed a non-relapse rate of 71.7% or 67.4%, respectively. Most of the generalized relapse appeared within five years following start of endocrine therapy in these advanced stages. The interval from relapse to prostate carcinoma-related death in patients with the generalized relapse was 9 approximately 21 months, and those in stage D tended to show a a poorer prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytochrome c release, mitochondrial membrane depolarization, caspase-3 activation, and Bax-alpha cleavage during IFN-alpha-induced apoptosis in Daudi B lymphoma cells.

Interferon-alpha (IFN-alpha) displays antitumor action by inducing direct cytotoxicity against tumor cells in addition to generation of cytotoxic cells. The IFN-alpha-induced direct cytotoxicity is at least partly due to induction of apoptosis. In the present study, we examined signaling pathways implicated in IFN-alpha-induced apoptosis in Daudi cells. Release of cytochrome c from mitochondria to cytosol was found after 12 h incubation with IFN-alpha, followed by a decline in mitochondrial membrane potential (Delta psi(m)) and procaspase-3 activation at 24 and 36 h, respectively. Cleavage of endogenous Bax-alpha (21 kDa), generating an 18-kDa fragment (p18 Bax-alpha), was found at 36 h. Although the endogenous p21 Bax-alpha was located in both cytosol and mitochondrial membranes, the p18 Bax-alpha resided only on mitochondrial membranes. IFN-alpha-induced apoptosis occurred 48 h after stimulation, with a further increase in proportion up to 72 h. Pretreatment with pancaspase inhibitor Z-VAD-fmk substantially inhibited the IFN-alpha-mediated Bax-alpha cleavage and apoptosis, but not the decline in Delta psi(m), suggesting the possibility that caspase-3 activation is implicated in the Bax-alpha cleavage, probably leading to amplification of the apoptotic processes. Our results suggest that modulation of endogenous p21 Bax-alpha is implicated in IFN-alpha-induced apoptosis.