Fusion vaccine therapy by IL-2-gene-transduced dendritic cells and tumor cells

We evaluated the usefulness of fusion vaccine prepared from IL-2-gene-transduced splenic dendritic cells (DCs) and fibrosarcoma tumor cells (QRsP) in treating of lung metastasis. The IL-2 or LacZ gene was transferred into spleen-derived DCs using an adenoviral vector. Irradiated QRsP tumor cells were fused with IL-2 gene transduced DCs (fusion/IL-2) or LacZ gene transduced DCs (fusion/LacZ) by polyethyleneglycol. These fusion cells expressed major histocompatibility complex (MHC) class I and MHC class II, CD86, CD11c and CD8alpha. IFN-gamma and cytotoxic T lymphocyte (CTL) activity of splenic lymphocytes in mice vaccinated with fusion cells increased significantly as compared with those of DC or tumor cells vaccinated mice. CTL levels in fusion/IL-2-vaccinated mice were higher than that in fusion/LacZ-vaccinated mice. The number of lung metastasis in the fusion/IL-2 or fusion/LacZ-vaccineatd mice was significantly lower than that in mice vaccinated with DCs, tumor or PBS. The introduction of the IL-2 gene into fusion cells produced more potent therapeutic effects. Our results suggest that the fusion cells prepared from IL-2 gene transduced spleen derived DCs and tumor cells have the ability to induce therapeutic effect against lung metastasis.     

Rectovaginal fistulas after rectal cancer surgery: Incidence and operative repair by gluteal-fold flap repair

BACKGROUND: We investigated the correlation between operative procedures for rectal carcinoma and postoperative rectovaginal fistulas (RVF), and treatment for RVF. METHODS: The medical records of 161 female patients with rectal carcinoma were examined retrospectively with respect to the cause, incidence, and methods of treatment for RVF occurring after rectal cancer operations, and to the outcomes of gluteal-fold flap repairs for RVF. RESULTS: Of the 161 patients, 16 developed RVF clinically. The incidence of RVF was significantly higher in patients who were anastomosed by the double stapling technique (DST) and had concomitant resection of the vaginal wall. No statistical difference was found between the established diverting ostomy group and the no-stoma group. Six patients recovered by the establishment of a diverting ostomy only. The gluteal-fold flap technique was performed for 5 patients. No RVF recurrences were noted in these 5 patients. CONCLUSIONS: The incidence of RVF was higher in the patients who were anastomosed by DST or had concomitant resection of the vaginal wall. Although some RVFs heal with only fecal diversion, for patients in whom RVF is caused by involvement of the vaginal wall in the circular staple or intersphincteric resection, good results are obtained with the gluteal-fold flap repair technique.     

Novel treatment with oncolytic herpes simplex virus, 'HF10' against breast cancer

An oncolytic herpes simplex virus type 1 mutant, named HF10, has been isolated and evaluated for anti-tumor efficacy in syngeneic immuno-competent mouse models. We have found that the mutant virus can very effectively treat cancer, and that all of survived mice acquire resistance to rechallenge of the tumor cells. Since a number of studies have shown that HF10 is effective and safe for use in localized or peritoneally disseminated malignant tumors of non-neuronal origin, phase I/II clinical trials using HF10 have been initiated for patients with metastatic breast cancer. Preliminary data from the clinical trials are encouraging.     

Ciliary neurotrophic factor preferentially enhances spontaneous IgE production by B cells from atopic patients

The effect of ciliary neurotrophic factor (CNTF) on IgE production by purified B cells from atopic patients was studied. CNTF significantly enhanced spontaneous IgE production by B cells from patients with atopic eczema/dermatitis syndrome (AEDS) in a dose-dependent fashion, and maximum enhancement was achieved at 1 ng/ml. CNTF-induced enhancement of IgE production was blocked by anti-CNTF mAb or anti-gp 130 mAb, but not by anti-IL-6 mAb. On the other hand, CNTF did not significantly enhance spontaneous production of IgGl, IgG2, IgG3, IgG4, IgM, IgAl or IgA2 by B cells from AEDS patients. In contrast to B cells from AEDS patients, B cells from non-atopic subjects failed to produce IgE spontaneously, and CNTF did not induce IgE production by non-atopic subjects' B cells. B cells from atopic patients contained surface IgE positive B cells (sIgE+ B cells), which spontaneously produced IgE, while surface IgE negative B cells (sIgE- B cells) failed to do so. CNTF enhanced IgE production by sIgE+ B cells from patients with AEDS, allergic rhinitis or bronchial asthma, while CNTF failed to induce IgE from sIgE- B cells from these patients. Stimulation of sIgE- B cells with IL-4 plus anti-CD40 mAb induced IgE production. However, stimulation of sIgE- B cells with CNTF plus IL-4, or CNTF plus anti-CD40 mAb did not induce IgE production by sIgE- B cells. Collectively, these results indicate that CNTF preferentially enhanced spontaneous IgE production by post-switched sIgE+ B cells, while CNTF failed to induce IgE by pre-switched sIgE- B cells. These results suggest that CNTF may be involved in the allergic diseases.     

Effect of egg yolk antibody on experimental Cryptosporidium parvum infection in scid mice

In this study the effect of chicken egg yolk antibody (IgY) against Cryptosporidium parvum infection was examined. IgY sample was prepared from eggs of chickens immunized with C. parvum oocyst antigens. In vitro, antibody-treated sporozoites showed reduced binding to Caco-2 cells and lost vitality. These phenomena were not observed with a control IgY sample prepared from eggs of non-immunized chickens. Scid mice orally administered with the antibody demonstrated partial reduction in oocyst shedding after challenge with 10(3) oocysts. IgY, however, could not eliminate the infection after 17 days of continuous treatment. The potentials of using specific IgY for treatment and prevention of cryptosporidiosis were discussed.     

Inhibition of syk activity and degranulation of human mast cells by flavonoids

To investigate the effect of flavonoids on the activation of p72(syk) (Syk) protein tyrosine kinase which plays a pivotal role in the high affinity IgE receptor-mediated degranulation of mast cells, we picked out 10 flavonoids, classified them into 4 series, and examined their effects on the activation of Syk and on the degranulation of human mast cells. Flavones and flavonols showed clear inhibition, whereas flavanones and isoflavones had either weak or no effect on Syk enzymatic activity induced by amino acid peptide corresponding to the activation loop domain and on IgE-dependent degranulation of human cultured mast cells (HCMC). On the basis of calculated logP (ClogP) values as a prediction of compound lipophilicity, some flavonoids were speculated to have low lipophilicity, the reason for poor cell permeability. A significant relationship was observed between the inhibition of Syk activity and HCMC degranulation attributable to flavonoids when the ClogP values of the compounds were taken into account (r(2)=0.89). These results suggested that the impairment of mast cell degranulation by several flavonoids classified into flavones and flavonols might be mediated via inhibition of the intracellular activation of Syk.     

Influence of coronary artery disease risk factors on baroreflex sensitivity in the elderly

Abstract. In this study, we assessed whether baroreflex sensitivity (BRS) is influenced by risk factors of cardiovascular disease. Subjects of this study were 95 elderly people (40 males and 55 females; mean age ± SD, 66.6±1.6 years) who underwent a medical check-up. BRS was determined as the gain of transfer function in baroreflex arc by spectral analysis of mean blood pressure and R-R interval variabilities in low-frequency band (0.04–0.15 Hz). Gender-related differences in BRS and relationships between BRS and various risk factors of cardiovascular disease were investigated. The value of BRS was significantly higher in males [10.7±3.7 (SD) ms/mmHg] than in females [9.0±4.0 ms/mmHg, p< 0.05]. However, this gender-related difference disappeared when other variables were taken into account in the multivariate model. Multiple regression analyses showed independent inverse relationships between BRS and heart rate [b=–0.016±0.004 (SE) bpm, =–0.39], and between BRS and platelet count [b=–0.002±0.001 × 103/µl, =–0.22]. Our results indicated that BRS is inversely related to platelet count in the elderly population. The precise mechanism of this correlation is unknown, but platelet factors released from platelet aggregates can potentially influence vascular function and modify BRS, or there is a common underlying determinant responsible for the covariation.