Bath-PUVA therapy decreases infiltrating CCR4-expressing tumor cells and regulatory T cells in patients with mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is a malignant lymphoma characterized by expansion of CD4(+) memory T-cell clones. Infiltrating cells express CCR4, which is attracted to CC chemokine ligands 17 and 22 (thymus and activation-regulated chemokine [TARC]/CCL17 and TARC/CCL22). Bath-psoralen plus ultraviolet A (PUVA) is effective against MF. In patients with psoriasis, bath-PUVA induces circulating regulatory T cells (Tregs), which suppress effector T cells. To understand the mechanisms in MF, we analyzed lesion-infiltrating cells before and after bath-PUVA therapy. PATIENTS AND METHODS: Thirteen patients with MF (12 stage IB, 1 stage III; mean age 69.2 years, range 35-87 years; 6 men, 7 women) were recruited. RESULTS: Immunohistochemical analysis revealed that lesion CCR4-positive (CCR4(+)) cells and Tregs significantly decreased from 105.1 ± 164.8 cells/10(-2) mm(2) to 31.4 ± 39.0 cells/10(-2) mm(2) and from 78.1 ± 67.8 cells/10(-2) mm(2) to 24.7 ± 25.0 cells/10(-2) mm(2), respectively. Serum TARC levels significantly correlated with infiltrating CD3(+) (r = 0.997), CCR4(+) (r = 0.991), and forkhead box P3-positive (Foxp3(+)) cells (r = 0.843). Circulating Tregs before bath-PUVA therapy were not significantly different from those in healthy volunteers. Bath-PUVA did not significantly change the percentage of circulating Tregs. CONCLUSIONS: Bath-PUVA decreased CCR4(+) cells and Tregs in MF lesions but did not induce circulating Tregs, which might suppress effector T cells. Direct effects through skin lesions might eliminate both pathogenetically relevant cells and Tregs. Systemic immunosuppression was not induced.

Bibliographical investigation of complementary alternative medicines for osteoarthritis and rheumatoid arthritis.

BACKGROUND: A variety of complementary and alternative medicine (CAM) treatments are provided to the elderly. We investigated the efficacy and safety of CAM substances that are available to patients with osteoarthritis (OA) and rheumatoid arthritis (RA), both in Japan and overseas. METHODS: Information on CAM products was collected from the World Wide Web, using the keywords "arthritis" and "supplement" in five languages (Japanese, English, French, Italian and German) using a popular search engine for each of the languages. References to published work on the products were researched using PubMed with the keywords of "arthritis", "anti-inflammatory" and "analgesics". Such published work was classified according to the evidence levels established by the Cochrane Library. RESULTS: Two-hundred and sixty CAM products for OA or RA were available in Japan, of which 41 CAM products had been tested in randomized controlled trials (RCT); there was no scientific evidence for the remaining 219 CAM products. Most of the previous RCT suggested that CAM was effective in OA or RA. Herein, we confirmed the significant OA relieving effects of chondroitin sulfate through a meta-analysis. Effectiveness was assessed using subjective scores, not disease-specific immunological or serological markers for assessment. Toxicological investigations had only been performed for a few CAM products. CONCLUSION: Some CAM products that are effective against RA may be used together with biological therapy. However, some of the CAM products available in Japan should be tested using objective markers. Some CAM products for OA could be used for the relief of pain.

Primary mucosa-associated lymphoid tissue lymphoma of the prostate: tumor relapse 7 years after local therapy.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is rare, and only five cases have been reported. Reported herein is a new case that has involved a 9 year follow up. A 79-year-old man was treated with transurethral resection (TUR) for a mass of the right prostatic lobe, and followed up under a diagnosis of benign prostatic hyperplasia with atypical lymphoid infiltration. Seven years later TUR was again performed for a right lobe mass. The lesion was diagnosed as a relapsed MALT lymphoma after detailed histological and immunoglobulin heavy chain gene analyses of the initial and relapsed lesions. Interestingly, lymphoepithelial lesions were observed only infrequently in this tumor. The API2-MALT1 fusion, a gene alteration specific to MALT lymphoma, was absent. The patient had stage IA disease at the time of tumor relapse, and has been alive and well for the 2 years after the second TUR. The present case suggests that despite tumor recurrence, prostatic MALT lymphoma is indolent, and function-preserving therapy is warranted.

Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid.

Class II major histocompatibility complex (MHC II) is normally silenced in plasma/multiple myeloma (MM) cells at the transcriptional level through downregulation of class II transactivator (CIITA), allowing MM cells to escape from immunological responses. Here we demonstrate that a retinoic acid receptor-alpha/beta-selective retinoid Am80 (tamibarotene) could induce the expression of functional MHC II molecules in human MM cell lines. Am80 upregulated expression of the interferon regulatory factor-1 gene, followed by enhancement of CIITA expression. This is the first report demonstrating that retinoid can induce the expression of MHC II in terminally-differentiated plasma/MM cells.

Effect of dietary antioxidants and risk of oral, pharyngeal and laryngeal squamous cell carcinoma according to smoking and drinking habits.

Several intervention trials and prospective studies have reported that beta-carotene supplementation is not associated with a decreased risk of several cancers among smokers and drinkers, and that it may even have adverse effects in these groups. The relationship between dietary antioxidant intake and the risk of head and neck squamous cell carcinoma (HNSCC) has been examined intensively, but little is known about the effects of antioxidants on HNSCC with respect to smoking and drinking habits. Here, we conducted a case-control study of 385 histologically confirmed cases of HNSCC (193 oral, 132 pharyngeal and 60 laryngeal), excluding nasal and paranasal cancer, and 1925 age-matched and sex-matched cancer-free outpatient controls using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center, Japan. The intake of nutrients and food groups was assessed with a food frequency questionnaire, and multivariate-adjusted odds ratios for cancer were estimated for smoking and drinking habits using logistic models. The results showed an overall inverse association between the intake of dietary antioxidants, including carotene, and vitamins C and E, and risk of HNSCC. The protective effect of these antioxidants was seen in both men and women. High consumption of antioxidants was associated with a decreased risk of HNSCC among smokers, drinkers and those with both smoking and drinking habits. These findings suggest that dietary antioxidant intake prevents HNSCC in smokers and drinkers.

Effect of nifedipine on C-reactive protein levels in the coronary sinus and on coronary blood flow in response to acetylcholine in patients with stable angina pectoris having percutaneous coronary intervention.

The effects of nifedipine on inflammation and endothelial function in the coronary circulation were studied in patients who had angina pectoris (n = 17). Long-term treatment with nifedipine (nifedipine CR, 20 mg/day for 4 months) decreased levels of C-reactive protein in the coronary sinus (from 0.35 +/- 0.09 mg/dl to 0.07 +/- 0.01 mg/dl, mean +/- SEM, p <0.05) and enhanced acetylcholine-induced increases in coronary blood flow. Thus, nifedipine is effective in decreasing inflammation and incresing endothelial function in the coronary circulation.

Antihypertensive effects of long-acting calcium channel blockers on hemodialysis days--a randomized crossover trial between benidipine and nifedipine CR.

BACKGROUND/AIMS: Since antihypertensive effects of most calcium channel blockers largely depend on their plasma concentrations, a rapid increase in blood pressure may occur as circulating levels of such blockers decrease after hemodialysis. Thus, the effects of benidipine and nifedipine CR (extended-release coated tablets, Adalat CR), which are long-acting calcium channel blockers, on post-hemodialytic blood pressures were investigated. METHODS: A randomized crossover trial was carried out with 10 hypertensive patients on chronic maintenance hemodialysis. Patients were assigned to receive benidipine (4-8 mg/day) or nifedipine CR (20-40 mg/day), and after 4 weeks, 24-hour ambulatory blood pressure monitoring was performed on the day of hemodialysis and blood samples were obtained before and after hemodialysis to measure plasma concentrations of the blockers. The calcium channel blockers were then exchanged in each patient and the same protocol was repeated. RESULTS: The pattern of fluctuation of blood pressure differed markedly between the treatment with benidipine and nifedipine CR. Under treatment with nifedipine CR, rapid increase in blood pressure was observed after hemodialysis, while blood pressure remained at favorable levels with benidipine. Plasma concentrations of the blockers were significantly decreased by hemodialysis. CONCLUSION: Benidipine exerts more sustained antihypertensive effects than expected from its disposition in plasma. The stable depressor effects of benidipine even after hemodialysis may contribute to favorable control of blood pressure in this population.

Frequent coinfection with hepatitis B virus strains of distinct genotypes detected by hybridization with type-specific probes immobilized on a solid-phase support.

A genotype-specific probes assay (GSPA) was developed for distinguishing the seven genotypes (A-G) of hepatitis B virus (HBV). Nucleotide (nt) sequences corresponding to preS1 region were amplified by PCR with a primer labeled with biotin, and delivered to eight wells on which complementary sequences specific to one or other genotype had been immobilized. Thereafter, hybridization of HBV DNA sequences amplified from the test serum was detected by colorimetry. When 256 sera from HBV carriers in Bangladesh, Cameroon, Japan, South Africa, USA and Uzbekistan were subjected to GSPA, genotypes were concordant with those of ELISA with monoclonal antibodies to epitopes on preS2-region products in 242 (94.6%) of them; 8 sera (3.1%) were not genotypeable by either method. Cloning analysis confirmed the presence of two distinct HBV genotypes in the seven selected sera with coinfection. There were 7 (2.7%) sera with discordant genotyping results between GSPA and ELISA. When HBV DNA clones propagated from these sera were sequenced and analyzed phylogenetically, the genotypes determined by GSPA were verified. Coinfection with HBV strains of two distinct genotypes was identified by GSPA in 28 (10.9%) sera, while it was suggested by ELISA in only 2 (0.8%) sera. The GSPA method would be particularly useful for detecting the coinfection with distinct HBV genotypes of any clinical relevance, which seems to be more frequent than reported previously.