Potential of dendritic-cell immunotherapy for relapse after allogeneic hematopoietic stem cell transplantation, shown by WT1 peptide- and keyhole-limpet-hemocyanin-pulsed, donor-derived dendritic-cell vaccine for acute myeloid leukemia

Induction of leukemia-specific immune responses is a promising treatment for acute myeloid leukemia. A 58-year-old woman received Wilms' tumor 1 (WT1) peptide- and keyhole limpet hemocyanin (KLH)-pulsed, donor-derived dendritic cell (DC) vaccination for AML relapse after allogeneic stem cell transplantation. The vaccination induced immune responses to the naive antigen KLH, whereas definitive immune responses to WT1 were not detected. Leukemia gradually progressed despite of vaccination. This study indicates that DC vaccination can induce an antigen-specific immune response in a patient after allogeneic stem cell transplantation, thus representing a viable strategy to induce antigen-specific immune responses in such patients.     

Diabetes is a predictor of coronary artery stenosis in patients hospitalized with heart failure

In patients with heart failure, coronary artery disease is the most common underlying heart disease, and is associated with increased mortality. However, estimating the presence or absence of coronary artery disease in patients with heart failure is sometimes difficult without coronary imaging. We reviewed 155 consecutive patients hospitalized with heart failure who underwent coronary angiography. The patients were divided into two groups: patients with (N = 59) and without (N = 96) coronary artery stenosis. The clinical characteristics and blood sampling data were compared between the two groups. The patients with coronary artery stenosis were older than those without. The prevalence of diabetes mellitus (DM), dyslipidemia and a history of revascularization was higher in the patients with coronary artery stenosis. Patients with coronary artery stenosis tended to have wall motion asynergy more frequently than those without. On the other hand, the prevalence of atrial fibrillation (AF) was lower in patients with coronary artery stenosis. The serum hemoglobin level and estimated glomerular filtration rate were lower in patients with coronary artery stenosis than in those without. In the multivariate analysis, DM (odds ratio 3.517, 95 % CI 1.601–7.727) was found to be the only the predictor of the presence of coronary artery stenosis in patients with heart failure. In conclusion, coronary imaging is strongly recommended for heart failure patients with DM to confirm the presence of coronary artery stenosis.     

TAFI polymorphisms at amino acids 147 and 325 are not risk factors for cerebral infarction

Thrombin-activatable fibrinolysis inhibitor (TAFI) was reported as an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). Its level in plasma appears to influence vascular disease. In addition, TAFI activity is strongly influenced by genetic polymorphism, especially at amino acids 147 and 325. We investigated whether these TAFI polymorphisms would act as a risk factor for cerebral infarction (CI) by examining 253 samples in which the diagnosis was cliniconeuropathologically confirmed. We found little that was statistically significant in terms of these polymorphisms among patients with no vascular problems or in a population-based control group. In the present study of an elderly Japanese group, our samples revealed a lower percentage of the Ile allele at Thr/Ile-325 compared with western counterparts. Although patients with severe infarcts had a lower percentage of the Ile allele (10%) at amino acid position 325 compared with the slightly and moderately affected patients and the population-based control group (15-18%), no statistical significance was found. None of our results showed any statistical correlation between TAFI polymorphisms and CI.     

Hydrogen-rich saline solution attenuates renal ischemia�Creperfusion injury

Purpose  

Renal ischemia–reperfusion (I/R), an important cause of acute kidney injury, is unavoidable during various types of operations, including renal transplantation, surgical revascularization of the renal artery, partial nephrectomy, and treatment of suprarenal aortic aneurysms. Exacerbation of I/R injury is mediated by reactive oxygen species (ROS). A recent study has shown that hydrogen has antioxidant properties. In this study, we tested the hypothesis that a hydrogen-rich saline solution (HRSS) attenuates renal I/R injury in a rodent model.     

Conversion of atrial flutter to sinus rhythm during landiolol infusion

A 73-year-old male patient with a past history of hypertension and atrial premature contraction underwent endoscopic restoration of the left bubonocele. Sinus rhythm was confirmed by preoperative electrocardiography, but paroxysmal atrial flutter developed when abdominoscopy was started. Continuous administration of landiolol hydrochloride at a dose of 0.005 mg kg⁻¹ min⁻¹ after a loading dose of 0.04 mg kg⁻¹ min⁻¹ for 1 min resulted in control of heart rate without a decrease in blood pressure. Atrial flutter was converted to sinus rhythm 3 min after the start of administration. Landiolol hydrochloride was administered continuously until the morning of the following day and sinus rhythm was maintained postoperatively.     

Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system

To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy’s induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.