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Understanding the T-cell responses involved in inhibiting COVID-19 severity is crucial for developing new therapeutic and vaccine strategies. Here, we characterized SARS-CoV-2 spike-specific CD8+ T cells interacting with overlapping peptides on peripheral blood mononuclear cells from acute-phase COVID-19 patients. Relative to severe COVID-19, patients with mild COVID-19 had more frequent antigen-specific CD8+ T cells, and significantly increased SARS-CoV-2 spike-specific CD8+ T cells simultaneously expressing granzyme A, granzyme B, and perforin, suggesting that inducing highly cytotoxic CD8+ T cells during early infection suppresses COVID-19 severity. The BNT162b2 mRNA vaccine induced these antigen-specific CD8+ T cells in healthy donors, although lesser than in infected patients, and the induced subpopulation was not maintained long-term after second vaccination. Importantly, these CD8+ T cells showed cross-reactivity with the Delta and Omicron strains of SARS-CoV-2. Incorporating factors that efficiently induce CD8+ T cells with polyfunctional cytotoxic activity may improve future vaccine efficacy against such variants.

The current process of meat production using livestock has significant effects on the global environment, including high emissions of greenhouse gases. In recent years, cultured meat has attracted attention as a way to acquire animal proteins. However, the lack of markers that isolate proliferating cells from bovine tissues and the complex structure of the meat make it difficult to culture meat in a dish. In this study, we screened 246 cell-surface antibodies by fluorescence-activated cell sorting for their capacity to form colonies and their suitability to construct spheroid “meat buds”. CD29+ cells (Ha2/5 clone) have a high potency to form colonies and efficiently proliferate on fibronectin-coated dishes. Furthermore, the meat buds created from CD29+ cells could differentiate into muscle and adipose cells in a three-dimensional structure. The meat buds embedded in the collagen gel proliferated in the matrix and formed large aggregates. Approximately 10 trillion cells can theoretically be obtained from 100 g of bovine tissue by culturing and amplifying them using these methods. The CD29+ cell characteristics of bovine tissue provide insights into the production of meat alternatives in vitro.

Bone remodeling is precisely controlled by bone formation and bone resorption, and osteoblasts are responsible for both processes. Osteoblasts exhibit an osteoclastogenic phenotype in response to elevated intracellular cyclic AMP [cAMP]i levels. However, the role of cAMP in osteoblasts acquiring an osteogenic phenotype is controversial. To elucidate the effect of cAMP on both phenotypes, an osteoblast-like cell line, TMS-12, was established in our laboratory and used in this study. Dibutyryl-cAMP (dBcAMP), a cAMP analogue, inhibited mineralization in TMS-12 cells and MC3T3E1 cells (an osteoblast-like cell line) but promoted osteoclast-supporting activity in TMS-12 cells. Moreover, mineralization was inhibited in glucagon receptor-transduced TMS-12 cells (TMS-12GCGR) after glucagon treatment to increase endogenous [cAMP]i levels. However, the osteoclast-supporting activity of TMS-12GCGR cells was stimulated by glucagon treatment. These cAMP-induced phenotypic changes of osteoblasts were also supported by their gene expression profile. These results suggest that [cAMP]i is an important factor mediating phenotypic changes of osteoblasts. Our findings may provide valuable insights into the mechanisms that underlie bone remodeling in both, healthy and diseased states.

This study aimed to identify characteristics of impressive scenes for nursing students during clinical training. We asked 70 nursing students to write a reflective journal (RJ) on the most impressive scenes during nursing practice. The obtained data were qualitatively analyzed using the Qualitative Synthesis Method (KJ method). As most impressive scenes during clinical practice, [difficulty in dealing with needs of patients : embarrassment of unexpected true needs of patients], [difficulty in dealing with patients who does not get communication : embarrassment of difficulty in dealing with patients who ask questions repeatedly and uncooperative patients], [experience that put burdens on patients : burden in patients that was caused by insufficient understanding of patient's health status] , [experience that care was refused by patient's : patient's unexpected negative response to thoughtful care], ,[confusion and participation in the treatment of patients : pleasure that was able to participate in care by the advice of nurse], and [acceptance by the patients : a good response to the care and acceptance by the patients] were extracted from RJs of 36 nursing students (valid responses: 35). The nursing students encounter various unexpected events during the training that they have never experienced before. The results showed that such unseen situations leave a deep impression on students, and contribute to new learning.

The aim of this trial was to verify the new surgical device (the LigaSure vessels sealing system) decrease liver transection time.Among the major goals in hepatic resection are minimization of the operation time and of the blood loss. Preliminary reports have suggested that the vessel sealing system might decrease the liver transection time, which is directly associated with the amount of blood loss.Patients who were scheduled to undergo hepatic resection at the Tokyo University Hospital were assigned, by the minimization method, to either use of the new vessel sealing system (VS group) or the conventional clamp crushing method (CC group) for liver transection. The primary end point was the liver transection time, and the secondary endpoints were the amount of blood loss during the entire operation and during liver transection, length of hospital stay, postoperative liver function, and the incidence of various adverse events. An English-language summary of the protocol was submitted (registration ID: C000000337) to the Clinical Trials Registry managed by the University Hospital Medical Information Network in Japan, which can be accessed commission-free on the internet (Available at: http://www.umin.ac.jp/ctr/index.htm).From February to December in 2006, a total of 165 patients underwent liver resection for some benign or malignant disease of the liver. Among these patients, 120 were randomly assigned to the CC (n = 60) or the VS (n = 60) group. There was no mortality in either of the 2 groups. The median liver transection time in the VS group was 57 minutes (range: 11-127), similar to that in the CC group (56 [range: 9-269] min, P = 0.64), while there was no difference in the transection speed between the 2 groups (1.16 [0.15-2.26] cm/min vs. 1.10 [0.15-2.66] cm/min, P = 0.95). The amount of blood loss and blood loss per transection area during liver transaction in the VS group was also similar to that in the CC group (median: 315 [25-2415] mL vs. 315 [10-1700] mL; P = 0.80) and (5.04 [1.01-44.2] mL/cm vs. 4.36 [0.15-50.5] mL/cm; P = 0.14), respectively.This randomized controlled trial showed that while the vessel sealing system was safe, its use was not associated with any significant decrease of the operation time or blood loss during liver transaction as compared with that of the clamp crushing method.

To resect a small liver tumor located in the paracaval portion, we adopted transhepatic enucleation, i.e. enucleation of the tumor from the transected plane along the main portal fissure. In contrast to caudate lobectomy, this procedure can save dissection around the liver and vena cava, which would increase operation time and blood loss especially in repeat surgery after removal of Couinaud’s segment VII or the right lateral sector. It can also minimize the liver parenchymal volume to be resected. The transhepatic enucleation would be a safe and recommendable surgical technique for a small paracaval tumor in repeat resection and/or in patients with poor liver functional reserve.

Epithelioid hemangioendothelioma (EH) of the liver is a rare tumor, generally considered to have low-grade malignancy. Little is known about its clinical behavior and the therapeutic strategy is not established. We report the case of a 36-year-old woman who underwent living donor liver transplantation for EH with splenic metastases and died of recurrence 8 months later. To determine if transplantation improves the prognosis of patients with EH, we must re-evaluate its indications.

We report herein the case of a 32-year-old woman found to have a venous aneurysm originating from the ovarian vein. The patient presented with a 9-cm abdominal tumor, and surgery was performed under the preoperative diagnosis of a mesenteric cyst. The tumor was easily ablated from the mesentery and resected with the right ovarian artery and vein. His-tologically, the wall of the cyst showed the structure of a vein, and the diagnosis of a venous aneurysm was made. This disease is difficult to diagnose preoperatively when a patient presents with no symptoms other than a palpable mass, or when the lumen is obstructed by thrombus. This report serves to demonstrate that a venous aneurysm should be considered in the differential diagnosis of an asymptomatic abdominal mass.

A 69-year-old female was referred to our hospital with hematochezia. Dynamic computed tomography demonstrated a large tumor with rim enhancement and central necrosis that invaded into the transverse colon. The tumor was resected, and histopathological examination revealed mixed adenocarcinoma and squamous cell carcinoma with partial abscess formation. On the basis of a literature review and the findings from the present case, rim enhancement with central necrosis on imaging appears to be characteristic of this disease.

The extent of donor hepatectomy may affect splenic hypertrophy and platelet count. The subjects were 50 live liver donors. The ratio of the graft weight to total liver volume (GW/TLV) and the splenic hypertrophy ratio, expressed as the splenic volume one month after surgery divided by that before surgery, were calculated. The platelet count one month after surgery was divided by that before surgery to determine the rate of the platelet count decrease. The correlation of GW/TLV to the splenic hypertrophy ratio and the rate of the platelet count decrease were examined. The median (range) GW/TLV was 54 (28-71)%. The splenic hypertrophy ratio and the rate of the platelet count decrease was 133 (99-191)% and 92 (71-129)%, respectively. GW/TLV positively correlated with the splenic hypertrophy ratio (Spearman's correlation coefficient (r(s)) = 0.448, p = 0.001), and negatively correlated with the rate of the platelet count decrease (r(s) = -0.471, p < 0.001). Multivariate analysis revealed that GW/TLV influenced the splenic hypertrophy ratio [adjusted odds ratio (OR), 12.0; 95% confidence interval (CI), 1.32-9.04; p = 0.01] and the ratio of the platelet count decrease (adjusted OR, 11.6; 95% CI, 1.40-8.33; p = 0.01). Larger graft procurement might place living liver donors at higher risk for post-operative thrombocytopenia.

Conversion of the main immunosuppressive agent from tacrolimus to cyclosporine (CyA) is a valuable rescue therapy for the severe adverse effects of tacrolimus. We report our experience of the conversion in living donor liver transplantation, in which tacrolimus therapy was converted to CyA. There are few reports describing the optimal initial dose of orally administered CyA (PO CyA) after intravenously administered CyA (IV CyA). We retrospectively investigated the ratio of CyA blood concentrations at 12 hours after the initiation of PO CyA to that just before the conversion, and the ratio of the initial dose of PO CyA to the total dose of IV CyA administered during the 12 hours before the conversion. Linear regression analysis revealed a close correlation between these ratios (y = 2.7 + 5.8x, r = 0.73; P = .002). We recommend that, to maintain a similar trough level of CyA during conversion in liver transplantation, Neoral should be initiated at a ninefold greater dose than the total dose of IV CyA administered during the 12 hours before conversion.

Hepato-pancreaticoduodenectomy was performed for common bile duct carcinoma associated with celiac axis stenosis. To secure arterial blood flow to the upper abdominal organs, we preserved the anterior arcade in the pancreas head acting as a collateral pathway between the superior mesenteric artery and the celiac artery. This is another valid alternative procedure for pancreaticoduodenectomy in a patient with celiac axis stenosis.

Summary Although living donor liver transplantation (LDLT) is accepted as an alternative therapy for primary biliary cirrhosis (PBC), the postoperative results are not well known. Fifty patients with PBC underwent LDLT at Tokyo University Hospital. Their clinical records were retrospectively analyzed. Postoperative death occurred in four patients within 2 months (mortality, 8%), while later death occurred in three patients. In the median follow-up period of 35 months (range 4-84 months), the 1, 3, and 5-year overall survival rates were 90%, 88%, and 80%, respectively. The laboratory data indicated that graft function was sufficient. No recurrence of PBC was confirmed. Multivariate analysis indicated that an updated Mayo score of

Benign or malignant stricture of extrahepatic bile ducts may result when small intrahepatic bile ducts are anastomosed to the jejunal loop after resection of extrahepatic bile ducts, hepatic parenchyma, and intrahepatic bile ducts. We applied a parachute technique, which has been used for fine vascular anastomosis, to hepaticojejunostomy in eight patients with either extrahepatic bile duct carcinoma or intrahepatic cholangiocellular carcinoma. One to four small bile ducts were anastomosed to the jejunal loop. No patient experienced a complication due to this anastomosis. Postoperative elevation of the serum bilirubin was transient, and all patients were discharged within 36 days after surgery. Although the follow-up period in this series is not yet long enough to evaluate the long-term outcome of this technique, the ease of the hepaticojejunostomy and good short-term results warrant farther clinical investigation of this technique.

We describe a new cystatin in both mice and humans, which we termed leukocystatin. This protein has all the features of a Class II secreted inhibitory cystatin but contains lysine residues in the normally hydrophobic binding regions. As determined by cDNA library Southern blots, this cystatin is expressed selectively in hematopoietic cells, although fine details of the distribution among these cell types differ between the human and mouse mRNAs. In addition, we have determined the genomic organization of mouse leukocystatin, and we found that in contrast to most cystatins, the leukocystatin gene contains three introns. The recombinant proteins corresponding to these cystatins were expressed in Escherichia coli as N-terminal glutathione S-transferase or FLAGTM fusions, and studies showed that they inhibited papain and cathepsin L but with affinities lower than other cystatins. The unique features of leukocystatin suggests that this cystatin plays a role in immune regulation through inhibition of a unique target in the hematopoietic system.

Secondary pancreaticoduodenectomy was performed in 2 patients, 1 who had undergone proximal gastrectomy for a gastric carcinoma and 1 who had undergone subtotal esophagectomy with stomach tube reconstruction for an inferior thoracic esophageal carcinoma. To prevent ischemia and congestion of the remnant stomach, the inflow and outflow pathways to the stomach, such as the right gastroepiploic artery and vein, were preserved. In this article, we describe the preservation procedures and discuss the problems of the secondary abdominal surgical procedure.