Gene expression profiling of diffuse large B-cell lymphoma supervised by CD21 expression

This study investigated the gene expression profiles of 40 cases of diffuse large B-cell lymphoma (DLBCL) according to CD21 expression, a favourable prognostic factor in DLBCL. Signature genes were analysed by Gene Ontology Tree Machine, and genes concerned with the immune system and related categories were significantly upregulated in CD21⁻ DLBCLs. Of 40 DLBCLs, four were germinal centre B cell-like (GCB) and 36 non-GCB. Of the 36 non-GCB DLBCLs, 14 CD21⁺ DLBCLs showed significantly better overall survival than the 22 CD21⁻ DLBCLs ( P  =   0·036). Hierarchical cluster analysis of signature genes related to CD21 was applied to previously published data sets, resulting in two groups for each data set, CD21⁺ type DLBCLs and CD21⁻ type DLBCLs. Survival of CD21⁺ type DLBCLs was significantly better than that of CD21^– type ( P  =   0·006 and P  =   0·004, respectively). In both data sets, CD21⁺ type DLBCLs predominantly included GCB DLBCLs compared with CD21⁻ type. The top classifier gene of CD21 expression was IGHM, and the five of nine Gene Ontology categories significant in CD21^– DLBCLs included IGHM . Immunohistochemical analysis of 216 DLBCLs confirmed that overall survival of surface (s) IgM⁺ DLBCLs was significantly poorer than that of sIgM^- DLBCLs ( P  =   0·013).     

Expression of monocyte chemoattractant protein-1 in idiopathic dilated cardiomyopathy

Atrial fibrillation (AF) is the most common arrhythmia in clinical practices. Mediated by muscarinic type 2 receptors (M(2)Rs), acetylcholine affects electrophysiological activities of atrial myocytes and may contribute to the onset of AF. In order to characterize the distribution of M(2)Rs in the atrial myocardium, different atrial regions in both the SD rat and human were dissected. Atrial myocytes were isolated with type II collagenase. The M(2)Rs expression in these atrial tissues and myocytes was detected by immunofluorescent staining and confocal laser scanning biological microscope. The results showed the highest density of M(2)Rs in atrial myocytes of the left atrial posterior wall. It is concluded that there is a marked spatial heterogeneity in the expression of the M(2)Rs in the atrium, which might create a substrate that would favor the initiation and maintenance of acetylcholine-induced AF.     

Impact of obesity on the surgical outcome following repeat hepatic resection in Japanese patients with recurrent hepatocellular carcinoma

AIM： To evaluate the impact of obesity on the postoperative outcome after hepatic resection in patients with hepatocellular carcinoma （HCC）. METHODS： Data from 328 consecutive patients with primary HCC and 60 patients with recurrent HCC were studied. We compared the surgical outcomes between the non-obese group （body mass index： BMI 〈 25 kg/m2） and the obese group （BMI ≥ 25 kg/m2）. RESULTS： Following curative hepatectomy in patients with primary HCC, the incidence of postoperative complications and the long-term prognosis in the nonobese group （n = 240） were comparable to those in the obese group （n = 88）. Among patients with recurrent HCC, the incidence of postoperative complications after repeat hepatectomy was not significantly different between the non-obese group （n = 44） and the obese group （n = 16）. However, patients in the obese group showed a significantly poorer long-term prognosis than those in the non-obese group （P 〈 0.05, five-yearsurvival rate; 51.9% and 92.0%, respectively）. CONCLUSION： Obesity alone may not have an adverse effect on the surgical outcomes of patients with primary HCC. However, greater caution seems to be required when planning a repeat hepatectomy for obese patients with recurrent HCC.     

Comparison of dissolution profile and plasma concentration-time profile of the thalidomide formulations made by Japanese, Mexican and British companies

Thalidomide is an important advance in the treatment of multiple myeloma. In Japan thalidomide is now on the approval step for the treatment of multiple myeloma. The drug has some bothersome side effects such as defect of organogenesis, neuropathy, constipation and fatigue, but is likely more effective than standard chemotherapy and is changing multiple myeloma treatment. At this moment, Japanese patients must import the thalidomide preparations from Mexico, Britain and elsewhere, but after approval, they patients will be able to get the new Japanese thalidomide capsules. In order to determine appropriate amounts of Japanese thalidomide capsules in the treatment of multiple myeloma, we compared the dissolution profile and plasma thalidomide concentrations of Japanese and British capsules and Mexican tablets. The dissolution test was performed according to the Japanese and the United States Pharmacopoeia. The pharmacokinetic data for Japanese capsules were obtained from the clinical trial in Japanese subjects and compared with those data published for other formulations. The dissolution rate of the Japanese capsule was the fastest, followed by British and Mexican formulations. The pharmacokinetic profiles of Japanese and British capsules were similar, while the 100 mg Japanese thalidomide capsule demonstrated a 1.6-fold higher maximum plasma concentration than the 200 mg Mexican thalidomide tablet (1.7 vs. 1.1 microg/ml), greatly shortened t(max) (4.5 vs. 6.2 h), and the apparent half life was only one-third of the Mexican tablet (4.8 vs. 13.5 h). A comparison of the dissolution and the pharmacokinetic absorption profiles demonstrated a rank-order correlation. Physicians and pharmacists should be aware of the probable alteration in plasma thalidomide concentration when switching to the Japanese capsule, especially from the Mexican tablet, and should monitor clinical response carefully.     

Contribution of Translin to hematopoietic regeneration after sublethal ionizing irradiation

The integrity of the genome is threatened by DNA damaging events such as radiation, viral infection and chemicals. Ionizing irradiation is known to cause genotoxic damage through the generation of reactive oxygen species (ROS) and nitrogen species (RNS) and we have found that a signaling pathway for the nuclear translocation of Translin is initiated in association and efficiently blocked by a specific inhibitor of nitric oxide synthase (NOS). This suggests the involvement of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) in the nuclear translocation of Translin. To address the functional significance of Translin in the hematopoietic generation system after ionizing irradiation, we generated Translin-deficient (Translin(-/-)) mice and examined hematopoietic colony formation after sublethal ionizing irradiation. We thereby confirmed a severe delay of colony formation in the spleens of Translin(-/-) as compared with Translin(+/+) mice. Taken together, the results suggest that Translin contributes to hematopoietic regeneration by acting as a sensor protein for radiation-induced damage.