Evaluation of chromosomal abnormalities by cIg-FISH and association with proliferative and apoptotic indexes in multiple myeloma.

Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

Antipyretic activity of cinnamyl derivatives and related compounds in influenza virus-infected mice.

Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic activity by suppressing interleukin-1alpha production responsive to interferon in a murine intranasal influenza virus infection model. Using this model, antipyretic compounds with such novel biological activities were characterized from the herbs. The organic solvent-extractable fractions of Cinnamomum cassia among the herbs showed antipyretic activity. We selected six antipyretic compounds from 48 cinnamyl derivatives and related compounds that may be mainly involved in the fractions. Their antipyretic activity was significantly correlated with interleukin-1alpha regulatory activity. Four of them suppressed interleukin-1alpha production to a basal level and showed different mode of antipyretic action from that of aspirin in interleukin-1alpha-injected mice. Structure-bioactivity relationship of the four suggested that an ester bond played an important role for both antipyretic and interleukin-1alpha regulatory activities. These compounds may be useful in analyzing interleukin-1alpha-producing cells in fever production and the mechanism of defervescence by suppressing interferon-induced interleukin-1alpha production.

Cascade of fever production in mice infected with influenza virus.

The cascade of fever production in influenza was studied. To analyse fever production in a murine model, we selected DBA/2 mice that have the highest susceptibility in fibrile responses among seven mouse strains. Intranasal influenza infection- and interferon (IFN)-induced fever production was studied in this mouse model. Fever was induced prominently on day 2 after influenza infection and IFN activity was also increased in serum. Only the level of interleukin (IL)-1 alpha, an endogenous pyrogen, rose markedly in serum among cytokines (IL-1 alpha, IL-2, IFN-gamma, and tumor necrosis factor-alpha) examined. Fever was induced 14 hr after intraperitoneal IFN-alpha treatment and IL-1 alpha level rose significantly in the serum of the IFN-alpha-treated mice as compared with that of untreated mice. Fever production was significantly suppressed by treatment with anti-IFN-alpha/beta or anti-IL-1 alpha antibody in infected mice and the former significantly suppressed responsive IL-1 alpha production, indicating that elevated IFN activity induced IL-1 alpha production and subsequently fever production in infected mice. The activity of cyclooxygenase (COX) that produces prostaglandin (PG)E2 was significantly augmented in the brain of infected mice on day 2 after infection. Fever production was suppressed by the inhibition of COX activity with aspirin, although IL-1 alpha level was maintained at the elevated level. Therefore, influenza infection in mice turned on the following cascade for fever induction: IFN production, IL-1 alpha production, elevated COX activity, and PGE2 production. We elucidated the relationship among IFN activity, IL-1 alpha production and COX activity and demonstrated the cascade of fever production in influenza infection.

Antibodies to new cytoplasmic autoantigens: anti-JA, a potential marker for disease activity in systemic lupus erythematosus.

1. We describe new autoantibodies which recognize two cytoplasmic proteins of 30 and 26 kDa. They were detected by Western blot analysis in the sera of 6 of 79 randomly selected systemic lupus erythematosus (SLE) patients and are denoted anti-JA antibodies. This antibody specificity is different from the previously described lupus autoantibodies, anti-P and anti-S10. 2. The targeted autoantigens are trypsin sensitive, and resistant to RNase and DNase treatment. The binding to the antigens was not modified when reticulocyte ribosomes were prepared with protease inhibitors indicating that these are primary antigens and not degradation products. Several lines of evidence suggest that these proteins are almost certainly part of the ribosome. 3. Anti-JA reactivity was not observed in the sera from 60 patients with other autoimmune diseases or from normal individuals. In contrast, 55% of lupus sera selected for a high titer of anti-dsDNA (double stranded DNA) and LE cells were also anti-JA positive. 4. Anti-JA antibodies may be useful as a specific serological marker for disease activity in SLE. The strong association with anti-dsDNA antibodies and LE cell in the sera of SLE patients requires further study.

Antibodies to new cytoplasmic autoantigens: anti-ja, a potential marker for disease activity in systemic lupus erythematosus

We describe new autoantibodies which recognize two cytoplasmic proteins of 30 and 26 kDa. They were detected by Western blot analysis in the sera of 6 of 79 randomly selected systemic lupus erithematosus (SLE) patients and are denoted anti-JA antibodies. This antibody specificity is different from the previously described lupus autoantibodies, anti-P and anti-S10. The targeted autoantigens are trypsin sensitive, and resistant to RNase and DNase treatment. The binding to the antigens was not modified when reticulocyte ribosomes were prepared with protease inhibitors indicating that these are primary antigen and not degradation products. Several lines of evidence suggest that these proteins are almost certainly part of the ribosome. Anti-JA reactivity was not observed in the sera from 60 patients with other autoimmune diseases or from normal individulas. In contrast, 55% of lupus sera selected for a high titer of anti-ds DNA (double stranded DNA) and LE cells were also anti-JA positive. Anti-JA antibodies may be useful as a specific serological marker for disease activity in SLE. The strong association with anbti-ds-DNA antibodies and LE cell in the sera of SLE patients requires further study

[Clinical and biochemical characterization of isoniazid-induced auto-antibodies]. / Caracterização clínico-laboratorial de auto-anticorpos induzidos por isoniazida.

Isoniazid (INH) is one among many drugs capable of inducing autoantibodies and, in some cases, a lupus-like syndrome (LE). A longitudinal study was performed in 24 tuberculosis patients treated with INH to detect antibodies (A-AH) to total histones and fractions. Antinuclear antibodies were observed in two patients after treatment. Higher frequency of IgM-AH was also observed. IgM-AH binding to all fractions were observed in those serum samples exhibiting stronger ELISA reactivity. Conversely, binding to only H1 occurred when lower IgM-AH activity was tested. Correlations with clinical expressions of LE were not observed in the present study.