Lectin-like oxidized low-density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan-induced arthritis

OBJECTIVE: The relationship between rheumatoid arthritis and atherosclerosis has been recognized for >20 years. This study aimed to elucidate the roles of oxidized low-density lipoprotein (ox-LDL; one of the main pathogenic factors of atherosclerosis) and its endothelial receptor, lectin-like ox-LDL receptor 1 (LOX-1), in arthritic joints using a rat zymosan-induced arthritis (ZIA) model. METHODS: LOX-1 expression and ox-LDL accumulation in arthritic joints were detected by immunohistochemistry using specific mouse anti-LOX-1 and anti-ox-LDL monoclonal antibodies, respectively. To elucidate the effects of the expressed LOX-1 on arthritis, ZIA rats were treated with anti-LOX-1 antibody or normal mouse IgG. The severity of arthritis was analyzed by joint swelling. Cell infiltration, synovial hyperplasia, and proteoglycan losses were also determined by histologic scoring. Proinflammatory cytokine and nitrite levels in serum and joint fluid were also measured. RESULTS: Immunohistochemical study of ZIA demonstrated LOX-1 expression on synovial endothelium and postcapillary venules at 6 hours after the induction of inflammation, with maximum expression detected at 24 hours. LOX-1 was also expressed weakly on both joint cartilage and synovium. Ox-LDL, a ligand of LOX-1, was also detected in articular chondrocytes. Administration of anti-LOX-1 antibody, which blocks LOX-1 activity, suppressed joint swelling (by 33.5%), leukocyte infiltration, and joint nitrite accumulation at 24 hours, as well as cartilage destruction at 7 days, compared with control rats. CONCLUSION: LOX-1 induction in arthritic joints might play a role in promoting joint inflammation and cartilage destruction by mediating leukocyte infiltration into the arthritic joints of ZIA rats.     

A case of Cowden disease with a germline mutation in exon5 of PTEN gene diagnosed based on typical esophageal multiple polypoid lesions observed on a medical checkup

A man in his fifties had a medical checkup. Mucosal papillomatosis in his oral cavity and palmoplantar keratosis were observed. Esophagogastroduodenoscopy revealed multiple polypoid lesions both in the esophagus and stomach. In addition, colonoscopy showed schwannoma in the rectum. He underwent an operation for adenomatous goiter. At first his typical esophageal multiple polypoid lesion was a diagnostic cue to Cowden disease (CD). Other clinical findings convinced us that he was suffering from CD. He was, then, diagnosed as CD according to the criteria of International Cowden Consortium although he had no family medical history suspicious of CD. Interestingly, genetic testing revealed that the patient had a germline mutation in exon5 of PTEN on chromosome 10. It was a point mutation of C to T transition at codon130, resulting in nonsense mutation (CGA→TGA). A close follow-up, especially cancer surveillance, is necessary for him since CD is associated with a high risk of developing malignant disease. It is noted that the typical esophageal features can be a diagnostic cue to CD, as shown in the present case.     

Efficacy of photodynamic therapy with topical 5‐aminolevulinic acid using intense pulsed light for Bowen’s disease

Photodynamic therapy (PDT) with topical 5‐aminolevulinic acid (ALA) is reported to be an effective and safe treatment for superficial non‐melanoma skin cancers. We have developed an photodynamic therapy with topical δ‐aminolevulinic acid (ALA‐PDT) protocol using intense pulsed light (IPL) for treating Bowen’s disease (BD). Three patients diagnosed with BD by skin biopsy were recruited in this study. They received IPL treatment after 3 h of occlusive dressing with application of ALA. This protocol was repeated every 2 weeks for a total of five sessions. The treated areas did not show any signs of BD for more than 1 year; therefore, it appeared that the affected areas showed improvement in all the patients. No patients withdrew from the study because of side‐effects. ALA‐PDT with IPL as a light source is well tolerated by patients and is beneficial for treating BD.     

A case report of gastric small cell carcinoma with long survival time by adjuvant chemotherapy--reports of chemotherapy regimens for gastric small cell carcinoma

Gastric small cell carcinomas are rather rare. The incidence of small cell carcinomas of all histological types of gastric tumors is about 0.1%. Small cell carcinoma is a very aggressive cancer with a poor prognosis,and there is no effective chemotherapy to date. We experienced a case of small cell carcinoma of the stomach with relatively long survival from combination chemotherapy. A 75-year-old man underwent total gastrectomy, and liver metastasis was recognized 5 months postoperatively. We used combination chemotherapy with tegafur/gimeracil/oteracil potassium+cisplatin and irinotecan hydrochloride+cisplatin, and he has obtained a long survival time. We should gather more chemotherapy cases and establish some effective regimens for small cell carcinoma of the stomach.     

Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway

Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)₂D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)₂D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1α-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)₂D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)₂D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD.     

Intravenous γ-Globulin for Kawasaki Disease

We studied the effect of γ-globulin (IVGG) and aspirin (ASA) on the development of the coronary artery lesions (CAL) of Kawasaki disease (KD) in three different protocols. Within 29 days of the onset of KD the echocardiographic evidence of CAL had developed in 39–42% of the patients in the ASA group, but only in 13.7–20.8% of the patients treated with IVGG (200 or 400 mgγkgX5). In long-term follow-up observation of CAL of these patients the evidence of CAL in both the ASA and the IVGG group regressed gradually; however, the residual rate of CAL was significantly low in the IVGG group at all times up to 24 months after onset. These facts suggest that when using IVGG for KD, we should select a dose of intact γ-globulin, 1,000 mgγkg or more in total, to prevent the occurrence of CAL. We have demonstrated not only a significant reduction in the occurrence of CAL in patients treated with IVGG but a reduction in the residual rate of CAL for two years as compared with those treated by ASA.