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Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.

Unlabelled: The aim of this study was to prospectively measure liver stiffness with real-time tissue elastography in patients with nonalcoholic fatty liver diseases (NAFLD) and to compare the result with the clinical assessment of fibrosis using histological stage. One hundred and eighty-one prospectively enrolled patients underwent real-time tissue elastography, with the first 106 being analyzed as the training set and the remaining 75 being evaluated as the validation set. Hepatic and splenic elastic ratios were calculated and compared with stage of histological fibrosis. Portal hypertension (PH) was assessed. Real-time tissue elastography cut-off values by stage in the training set were 2.47 for F1, 2.67 for F2, 3.02 for F3, and 3.36 for F4. Using these cut-off values, the diagnostic accuracy of hepatic fibrosis in the validation set was 82.6%-96.0% in all stages. Only portal fibrosis correlated with the hepatic elastic ratio by multivariate analysis. The area under the receiver operating characteristic curve of elastic ratio better correlated than serum fibrosis markers in both early and advanced fibrosis stages. Patients with PH, defined by splenic elasticity, had early fibrosis. Patients with severe PH were found only in the group with cirrhosis., Conclusion: Real-time tissue elastography is useful in evaluating hepatic fibrosis and PH in patients with NAFLD., (Copyright © 2012 American Association for the Study of Liver Diseases.)

We describe anesthetic management of a patient with airway stenosis due to a tracheal tumor involving the carina. A 68-year-old man developed dyspnea and was scheduled for YAG laser surgery under general anesthesia. Awake fiberoptic intubation was selected for anesthesia induction, and percutaneous cardiopulmonary support (PCPS) was ready to be established prior to induction of anesthesia. Anesthesia was maintained with remifentanil (0.05 microg x kg(-1) x min(-1)) and propofol (2 mg x kg(-1) x hr(-1)), and spontaneous breathing was preserved throughout the surgical procedure. The operation was completed successfully without any adverse events, and PCPS was not used. In this patient, preservation of spontaneous breathing using remifentanil was found to be useful for airway management.

Visceral adipose tissue (VAT) inflammation has been linked to the pathogenesis of insulin resistance and metabolic syndrome. VAT has recently been established as a new component of the immune system and is involved in the production of various adipokines and cytokines. These molecules contribute to inducing and accelerating systemic insulin resistance. In this report, we investigated the role of B cell-activating factor (BAFF) in the induction of insulin resistance. We investigated BAFF levels in the sera and VAT of obese mice. In obese mice, the BAFF levels were preferentially increased in VAT and sera compared to these levels in normal control mice. Next, we treated mice with BAFF to analyze its influence on insulin sensitivity. BAFF impaired insulin sensitivity in normal mice. Finally, we investigated the mechanisms underlying insulin resistance induced by BAFF in adipocytes. BAFF also induced alterations in the expression levels of genes related to insulin resistance in adipocytes. In addition, BAFF directly affected the glucose uptake and phosphorylation of insulin receptor substrate-1 in adipocytes. We propose that autocrine or paracrine BAFF and BAFF-receptor (BAFF-R) interaction in VAT leads to impaired insulin sensitivity via inhibition of insulin signaling pathways and alterations in adipokine production.

We report a patient who developed ulcerative colitis during the course of primary biliary cirrhosis (PBC). PBC was diagnosed by liver histology when the patient was 31 years old, at which time no symptoms were observed. At 45 years of age, the patient complained of bloody diarrhea and abdominal pain, and she was diagnosed with ulcerative colitis by colonoscopy and histological examination. The patient had HLA-DRB1(*)1502 and (*)0802, which are associated with both diseases. Ulcerative colitis should be considered in the differential diagnosis of bowel disease in patients with PBC. The possible genetic associations between 2 diseases are also discussed.

We performed a right transthoracic subtotal esophagectomy with systemic three-field lymph node dissection, followed by reconstruction with a gastric tube shifted retrosternally into the left side of the neck, for esophageal cancer in a 62-year-old woman. The patient had an uneventful postoperative course until postoperative day (POD) 9, when a venous thrombosis originating from the left brachiocephalic vein and elongating to the left subclavian vein was detected occasionally on computed tomography scans, although there were no clinical symptoms. The left brachiocephalic vein seemed narrowed by compression from the reconstructed gastric tube, and this was considered the cause of the thrombosis. The patient was commenced on thrombolytic therapy, using urokinase, and on anticoagulation therapy, using heparin and warfarin. The thrombus had disappeared completely by POD 38. The anticoagulation therapy was continued for 6 months and no recurrence of the thrombosis has been detected in the 4 months since its completion.

A 71-year-old woman with diabetic neuropathy who had undergone amputation of the right lower leg for diabetic gangrene 4 years previously, experienced severe lightning pain in both legs during spinal anesthesia. She was scheduled for skin grafting for a burn ulcer on her left foot. Her preoperative physical examination revealed hypesthesia in both legs due to diabetic neuropathy. Spinal anesthesia was performed with a combined spinal-epidural needle at the L 4-5 interspace using 2.0 ml of 0.3% hyperbaric dibucaine in the left lateral position. The region of hypesthesia was spread below Th 4. Ten minutes later, she complained of severe lightning pain in both legs and midazolam 1 mg was administered intravenously against agitation. The severe lightning pain diminished after the administration of pentazocine 7.5 mg intravenously in the recovery room. There was no worsening of neurological findings 5 hours later when the effect of spinal anesthesia disappeared. This clinical picture seems to be different from that of reported cases of phantom limb pain during spinal anesthesia in which severe lightning pain occurred in both legs. This case suggests that patients with diabetic neuropathy might develop severe lightning pain during spinal anesthesia using dibucaine.

Mongrel dogs were divided into a neuroleptanesthesia group (n = 10) and a pentobarbital group (neuroleptanesthesia plus pentobarbital; n = 10). The dogs were subjected to stepwise hemorrhage increasing from 30 to 40 and 50 ml.kg-1. In the neuroleptanesthesia group, mean arterial pressure, and cerebral and coronary blood flow decreased. Furthermore the oxygen and hydrogen ion balance in both the brain and the myocardium was aggravated, even at 30 ml.kg-1 of hemorrhage. Compared to the neuroleptanesthesia group, mean arterial pressure, and cerebral and coronary blood flow showed a greater decrease, cerebral oxygen consumption was lower, and the brain and myocardial metabolism worsened similarly at equivalent hemorrhage in the pentobarbital group. These results suggest that pentobarbital in combination with neuroleptanesthesia reduces cerebral oxygen consumption, but does not improve cerebral metabolism in the state of acute hemorrhage due to simultaneous induction of severe circulatory depression.

Mongrel dogs were subjected to halothane or isoflurane to examine the relationship between systolic blood pressure and cerebral as well as myocardial metabolism. The oxygen and hydrogen ion balances in the brain were not disturbed in either group to the systolic blood pressure level of 70 mmHg and were well maintained in the isoflurane group below this level. The myocardial oxygen balance was not aggravated in either group, whereas, the myocardial hydrogen ion balance was disturbed in the halothane group at the systolic blood pressure level between 70 mmHg and 50 mmHg though it was preserved in the isoflurane group. These findings demonstrate that the systolic blood pressure not disturbing oxygen and hydrogen ion balances in the brain and myocardium is 70 mmHg during halothane or isoflurane anesthesia, while isoflurane anesthesia becomes advantageous at the systolic blood pressures below this level. While the myocardial metabolism is less affected by lowering of blood pressures than the cerebral metabolism, it seems important to secure cardiac functions to maintain metabolism in both organs.

We have investigated the possibility of introducing a new way to carry out in vitro mutagenesis. N4-Aminodeoxycytidine 5'-triphosphate was used in the Klenow enzyme-catalyzed chain elongation of a primer oligonucleotide hybridized to a lacZ alpha region of M13mp2 viral single strand DNA, and the possibility of inducing an efficient, randomly distributed point mutations into this particular genomic region was explored. On transfection of the resulting DNA into E. coli, mutant phages emerged at frequencies up to 1%. Analysis of the DNA sequences of the mutants has shown that single transitions, either A to G or G to A, were induced in a random fashion, thus providing data to show the possibility of using this method for production of mutant proteins having various single amino-acid changes in a defined domain.