Di-(2-ethylhexyl) phthalate suppresses IL-12p40 production by GM-CSF-dependent macrophages via the PPARα/TNFAIP3/TRAF6 axis after lipopolysaccharide stimulation.

Activation of peroxisome proliferator-activated receptor α (PPARα) by di-(2-ethylhexyl) phthalate (DEHP) has an anti-inflammatory effect. This study investigated the potential combined influence of PPARα, tumor necrosis factor α-induced protein 3 (TNFAIP3/A20), and tumor necrosis factor receptor-associated factor 6 (TRAF6) on interleukin (IL)-12p40 production by macrophages exposed to DEHP and stimulated with lipopolysaccharide (LPS). LPS upregulated IL-12p40 expression by granulocyte-macrophage colony-stimulating factor-dependent macrophages (on day 9 of culture), whereas adding DEHP to cultures significantly attenuated the response of IL-12p40 to LPS stimulation. PPARα protein was also reduced by DEHP. Interestingly, transfection of macrophages with small interfering RNA (siRNA) duplexes for PPARα, TNFAIP3/A20, or dual oxidase 2 restored the response of IL-12p40 protein to LPS stimulation in the presence of DEHP. siRNAs for various protein kinase Cs (PKCs) (α, ß, γ, or δ) also restored IL-12p40 production by macrophages exposed to LPS and DEHP. While LPS upregulated both IL-12p40 and TNFAIP3/A20 production, adding DEHP to cultures dramatically reduced IL-12p40 and TNFAIP3/A20 levels. Silencing of PKCα reduced TNFAIP3/A20 production, whereas PKCγ siRNA (but not PKCß or δ siRNA) significantly increased TNFAIP3/A20. TRAF6 was also attenuated by macrophages with DEHP. The PPARα/TNFAIP3/TRAF6 axis may have an important role in the mechanism through which DEHP reduces IL-12p40 production by LPS-stimulated macrophages.

Increased prevalence of penicillin-resistant viridans group streptococci in Japanese children with upper respiratory infection treated by beta-lactam agents and in those with oncohematologic diseases.

BACKGROUND: Viridans group streptococci, especially penicillin-resistant strains, have been emerging as pathogens of bacteremia in neutropenic patients with hematologic malignancies. OBJECTIVES: To survey the penicillin susceptibilities of viridans group streptococci in Japanese children with and without oncohematologic diseases and to evaluate the effect of the short term administration of beta-lactam agents on the antibiotic susceptibility. METHODS: We tested 113 isolates of viridans group streptococci by the microdilution method for the minimal inhibitory concentrations (MICs) to 10 antibiotics. We isolated 40 isolates from the throats of children with an upper respiratory infection (URI) before beta-lactam antibiotic treatment, 32 isolates after the treatment, 33 isolates in hospitalized children with oncohematologic diseases and 8 isolates from blood. RESULTS: Twenty-five isolates (62.5%) from the children with URI before treatment were penicillin-intermediate or -high level resistant (MIC > or = 0.25 microg/ml). The prevalence of those isolates after antibiotic treatment (87.5%) was significantly increased compared with that before treatment (P = 0.03). The prevalences of the penicillin-high level resistant isolates (MIC > or = 4 microg/ml) in the children with oncohematologic diseases (39.4%) and in the isolates from blood (62.5%) were significantly higher than that in the children with URI before treatment (12.5%) (P < 0.01). Decreased susceptibilities to other beta-lactam agents were observed in the penicillin-high level resistant strains. CONCLUSIONS: The high prevalence of penicillin-intermediate or -high level resistant viridans group streptococci in healthy Japanese children was documented. The administration of beta-lactam agents decreased the prevalence of penicillin-susceptible isolates in the children with URI. High prevalences of penicillin-high level resistant isolates were observed in the oncohematologic patients and in the isolates from blood.

Mitral regurgitation may be related with previous streptococcal infection.

UNLABELLED: We measured anti M protein antibody (AMPA) titres in children with idiopathic mitral regurgitation (MR), streptococcal infection, rheumatic fever (RF), post-streptococcal acute glomerulonephritis (AGN) and normal healthy children. We investigated the association of MR with streptococcal infection and whether high AMPA titres can be used as persisting evidence of previous streptococcal infection. AMPA titres were measured with an enzyme-linked immunosorbent assay. We found significantly higher antibody titres in patients with MR and in streptococcal infection, RF, and AGN than in healthy controls. In the MR group (n = 15), 54% patients had AMPA titres above the 90th percentile value that was found in normal controls. An elevated AMPA titre persisted for a long period even when the anti-streptolysin O titres had declined to normal in RF patients. Our data suggest that the high AMPA titres in MR should be further investigated to clarify the probable association with previous streptococcal infection. CONCLUSION: High AMPA titre is a risk factor for developing complications after streptococcal infection. Our serological evidence suggests that in some patients, MR may be related to previous streptococcal infection.

Identification of biclonal (duplex) leukaemic cells expressing either CD4+/CD8- or CD4-/CD8+ from a patient with adult T-cell leukaemia/lymphoma.

A 24-year-old Japanese woman was admitted to our hospital in 1987 with a chief complaint of skin eruptions, and was diagnosed as having chronic ATLL. In 1993 the leucocyte count increased gradually to 126.0 x 10(9)/l with 91.5% abnormal lymphocytes expressing two different types of antigenicity, either CD+/CD8- or CD4-/CD8+. Monoclonal integration of human T-cell lymphotropic virus type-I proviral DNA was detected at different sites of the genomic DNA in each cell type. These studies clearly indicate that CD4+/CD8- and CD4-/CD8+ leukaemic cells originated from two independent clones.

Insulin responsiveness to glucose and tissue responsiveness to insulin during lactation in dairy cows.

The hyperglycemic clamp and hyperinsulinemic euglycemic clamp techniques were conducted to assess insulin responsiveness to glucose and tissue responsiveness to insulin in lactating and nonlactating Holstein cows. In the hyperglycemic clamp experiment, blood glucose concentrations were clamped at 50 mg/dl above the pre-infusion values by variable rates of glucose infusion. The mean plasma insulin increments over the baseline (insulin responsiveness to glucose) during hyperglycemia were lower (P < .05) in lactating cows than in nonlactating cows (23 vs. 102 microU/ml). In the hyperinsulinemic euglycemic clamp experiment, insulin was infused at the constant rate of 6.0 mU.kgBW-1.min-1 for 2 hr, and glucose was concomitantly infused at a variable rate to maintain the pre-infusion concentrations of blood glucose. Glucose infusion rates (tissue responsiveness to insulin) were similar (3.2 mg.kgBW-1.min-1) for lactating and nonlactating cows. It is concluded that insulin responsiveness to glucose is reduced, and tissue responsiveness to insulin remains unchanged during lactation in Holstein cows.

[T-cell lymphomas of the skin: a study of 7 cases excluding mycosis fungoides and adult T-cell leukemia/lymphoma].

Seven cases of T-cell lymphomas of the skin, excluding mycosis fungoides and adult T-cell leukemia/lymphoma, treated at the Department of Dermatology, Miyazaki Medical College for the previous 5 years were studied. Five were males and 2 were females, with a mean age of 61 years. Six patients presented either multiple skin tumors or subcutaneous indurations. Histologically, all cases presented dense infiltrations of the tumor cells showing variable morphological characteristics. Surface markers were also variable, suggesting that these were not a single entity. Treatment consisted of chemotherapy in 5 cases and electron beam therapy in 5 (localized in 4 and generalized in 1). Complete remission was obtained in 5 cases. The mean period from the first examination to death in the three fatal cases was 11.7 months, and the mean period of observation from the first examination to the present time in 4 cases ranged from 12 months to 40 months. Clinicopathological characteristics of these cases were compared with those of adult T-cell leukemia/lymphoma.