Analysis of surface antigen expression of human immunoglobulin-secreting cells: phenotypic heterogeneity in normal counterparts of myeloma cells

Human myeloma cells are malignant counterparts of plasma cells which represent the most differentiated B cells. Myeloma cells are, however, heterogeneous in their surface antigen expression (Katagiri et al, 1984, 1985), which may reflect that normal plasma cells have a spectrum of differentiation. To test this hypothesis, immunoglobulin-secreting cells (ISC) of non-neoplastic nature were studied with regard to their surface antigen expression by using a combination of reverse haemolytic plaque assay and complement-dependent cytolysis. Non-neoplastic ISC were found to have a broad spectrum of differentiation stages from the immature type of CD20+, HLA-DR+, CD38+ in the peripheral blood to the mature type of CD20-, HLA-DR-, CD38+ in the bone marrow. In patients with polyclonal B cell activation (PBA), ISC showed a more immature antigen expression in comparison with ISC in normal controls or patients without PBA. The surface antigen development of ISC was clearly demonstrated throughout the stages in the analysis of mitogen-induced ISC in vitro. No significant difference in the surface phenotype of ISC was found among heavy chain classes. Thus, non-neoplastic ISC show a spectrum of differentiation similar to that of myeloma cells, depending on the site where ISC are located, and on the degree of PBA in vivo.     

Cutting error of the distal femur in total knee arthroplasty by use of a navigation system

The aim of this study was to evaluate the alignment of the distal femoral cutting surface using a navigation system to determine the accuracy of bone cutting. We evaluated 20 knees in 20 patients. After cutting the distal femur, the cutting surface was validated using the navigated cutting block adapter, and the angular difference between the cutting surface and that preoperatively planned in the sagittal and coronal planes was recorded. The average error of all knees was 1.6° ± 2.2° in extension, and 14 (70%) of 20 knees were cut in an extended position. Our tendency is to cut the distal femur in an extended position with the first femoral cut in the sagittal plane.     

CT-guided radiofrequency ablation of osteoid osteoma in the long bones of the lower extremity

AIM:To present our initial experience with computed tomography guided radiofrequency ablation(RFA) of osteoid osteoma(OO) in our institution.METHODS:RFA was performed on eight patients(5 males and 3 females) with clinically and radiologically diagnosed OO(femoral neck,n = 4;femoral diaphysis,n = 2;tibial diaphysis,n = 1;fibular diaphysis,n = 1).Ablation was performed using an electrode with a 10-mm exposed tip for a total of 4-6 min at a targeted temperature of 90 degrees Celsius.No cooling system was used.The intervention was accepted as technically successful if the tip of the electrode could be placed within the center of the nidus.We defined clinical success as a disappearance within 2 wk after treatment of symptoms that had manifested at presentation.RESULTS:All procedures were technically successful.No major or immediate complications were observed.Clinical success was achieved in six of eight patients in the first procedure.A second procedure was performed for two patients who had recurrent or continued pain,and one of these cases was successfully treated.The overall rate of success was 87.5%(7/8).No complication was observed.CONCLUSION:Our preliminary results indicate a favorable success rate and no complications and are compatible with the previous reports of RFA of OO.     

Electrocardiographic Assessment of Incident Atrial Fibrillation in Hemodialysis Patients

The prevalence and incidence of atrial fibrillation in hemodialysis patients have recently increased, but there are few evident predictors of incident atrial fibrillation in hemodialysis patients. The purpose of this study was to determine whether electrocardiographic findings can predict the development of atrial fibrillation in hemodialysis patients. A cohort of 299 patients (age, 63.1 ± 14.0 years; men, 59.2%; duration of hemodialysis, 80.3 ± 77.7 months) on hemodialysis therapy in December 2004 was included. To determine the incidence of atrial fibrillation, electrocardiographic findings were checked regularly every 1–3 months through December 2009. To detect paroxysmal atrial fibrillation, we examined electrocardiograms any time a patient had cardiac symptoms. Cox proportional hazard analysis was used to determine independent variables for the onset of atrial fibrillation. At the time of enrollment, 37 patients had pre‐existing atrial fibrillation, for a prevalence rate of 12.4%. On the other hand, newly developed atrial fibrillation during the 5‐year follow‐up was determined in 45 patients, for an incidence rate of 4.37/100 patient‐years. In multivariate analysis, age (hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.07) and the presence of a P‐terminal force >0.04 mm/s as an electrocardiographic finding (hazard ratio, 4.89; 95% confidence interval, 2.54 to 9.90) were independently associated with new‐onset atrial fibrillation. The prevalence and incidence rates of atrial fibrillation are high in maintenance hemodialysis patients. Age and the presence of a P‐terminal force >0.04 mm/s as an electrocardiographic finding may predict new‐onset atrial fibrillation in these patients.     

Short rigid scope and stereo-scope designed specifically for open abdominal navigation surgery: clinical application for hepatobiliary and pancreatic surgery

Background

We have reported the utility of an image display system using augmented reality (AR) technology in hepatobiliary surgery under laparotomy. Among several procedures, we herein report a system using a novel short rigid scope and stereo-scope, both designed specifically for open abdominal navigation surgery, and their clinical application for hepatobiliary and pancreatic surgery.

Methods

The 3D reconstructed images were obtained from preoperative computed tomography data. In our specialized operating room, after paired-point matching registration, the reconstructed images are overlaid onto the operative field images captured by the short rigid scopes. The scopes, which are compact and sterilizable, can be used in the operative field. The stereo-scope provides depth information. Eight patients underwent operations using this system, including hepatectomy in two, distal pancreatectomy in three, and pancreaticoduodenectomy in three patients. The stereo-scope was used in five patients.

Results

All eight operations were performed safely using the novel short rigid scopes, and stereo images were acquired in all five patients for whom the stereo-scope was used. The scopes were user friendly, and the intraoperative time requirement for our system was reduced compared with the conventional method.

Conclusions

The novel short rigid scope and stereo-scope seem to be suitable for clinical use in open abdominal navigation surgery. In hepatobiliary and pancreatic surgery, our novel system may improve the safety, accuracy and efficiency of operations.     

Arm span–height difference is correlated with gastroesophageal reflux symptoms in aged Japanese subjects

Previous studies have indicated an association between the symptoms of gastroesophageal reflux disease (GERD) and aging plus height. In this study we investigated whether the arm span–height difference was related to GERD symptoms with a focus on aged subjects in the general population, since the arm span reflects the height in young adulthood before decreasing due to vertebral deformities from aging. A total of 285 elderly individuals (105 females) who visited nursing homes for the elderly in Japan were enrolled in this study. The GERD symptoms were evaluated by the Frequency Scale for the Symptoms of GERD (FSSG). The body weight, height and arm span were measured, and information regarding medications and complications were reviewed in each nursing record. 50.5% of women had more than 3 cm of arm span–height difference. In contrast, only 37.3% of men had more than 3 cm of arm span–height difference. The FSSG scores indicated more than 70% of subjects complained of any GERD symptoms. There was a significant correlation between the FSSG score and the arm span–height difference in the subjects with more than 3 cm of arm span-height difference (r = 0.236; p = 0.012). The correlation between the arm span–height difference and the FSSG score was significant only in women in females in the present study. In conclusion, our findings indicate that vertebral deformity evaluated by the arm span–height difference might have some positive relationship to the pathogenesis of GERD symptoms in elderly Japanese individuals.     

SCD1 inhibition enhances the effector functions of CD8+ T cells via ACAT1-dependent reduction of esterified cholesterol

We previously reported that the inhibition of stearoyl-CoA desaturase 1 (SCD1) enhances the antitumor function of CD8⁺ T cells indirectly via restoring production of DC recruiting chemokines by cancer cells and subsequent induction of antitumor CD8⁺ T cells. In this study, we investigated the molecular mechanism of direct enhancing effects of SCD1 inhibitors on CD8⁺ T cells. In vitro treatment of CD8⁺ T cells with SCD1 inhibitors enhanced IFN-γ production and cytotoxic activity of T cells along with decreased oleic acid and esterified cholesterol, which is generated by cholesterol esterase, acetyl-CoA acetyltransferase 1 (ACAT1), in CD8⁺ T cells. The addition of oleic acid or cholesteryl oleate reversed the enhanced functions of CD8⁺ T cells treated with SCD1 inhibitors. Systemic administration of SCD1 inhibitor to MCA205 tumor-bearing mice enhanced IFN-γ production of tumor-infiltrating CD8⁺ T cells, in which oleic acid and esterified cholesterol, but not cholesterol, were decreased. These results indicated that SCD1 suppressed effector functions of CD8⁺ T cells through the increased esterified cholesterol in an ACAT1-dependent manner, and SCD1 inhibition enhanced T cell activity directly through decreased esterified cholesterol. Finally, SCD1 inhibitors or ACAT1 inhibitors synergistically enhanced the antitumor effects of anti-PD-1 antibody therapy or CAR-T cell therapy in mouse tumor models. Therefore, the SCD1–ACAT1 axis is regulating effector functions of CD8⁺ T cells, and SCD1 inhibitors, and ACAT1 inhibitors are attractive drugs for cancer immunotherapy.