Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen-activated protein kinase and protein kinase B pathways.

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

The Tol2 transposon system mediates the genetic engineering of T-cells with CD19-specific chimeric antigen receptors for B-cell malignancies.

Engineered T-cell therapy using a CD19-specific chimeric antigen receptor (CD19-CAR) is a promising strategy for the treatment of advanced B-cell malignancies. Gene transfer of CARs to T-cells has widely relied on retroviral vectors, but transposon-based gene transfer has recently emerged as a suitable nonviral method to mediate stable transgene expression. The advantages of transposon vectors compared with viral vectors include their simplicity and cost-effectiveness. We used the Tol2 transposon system to stably transfer CD19-CAR into human T-cells. Normal human peripheral blood lymphocytes were co-nucleofected with the Tol2 transposon donor plasmid carrying CD19-CAR and the transposase expression plasmid and were selectively propagated on NIH3T3 cells expressing human CD19. Expanded CD3(+) T-cells with stable and high-level transgene expression (~95%) produced interferon-γ upon stimulation with CD19 and specifically lysed Raji cells, a CD19(+) human B-cell lymphoma cell line. Adoptive transfer of these T-cells suppressed tumor progression in Raji tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared with control mice. These results demonstrate that the Tol2 transposon system could be used to express CD19-CAR in genetically engineered T-cells for the treatment of refractory B-cell malignancies.

Treatment of superior mesenteric artery portal vein fistula with balloon-expandable stent graft.

Visceral artery to portal vein arteriovenous fistulas are rare and difficult to treat. Covered stents have made treatment of pseudoaneurysms and arteriovenous fistulas feasible utilizing minimally invasive techniques. We present a case of a 46-year-old male with a remote history of an exploratory laparotomy after a motorcycle accident who presented with abdominal pain, malaise, and jaundice. A computed tomographic scan revealed a superior mesenteric artery to portal vein arteriovenous fistula. A large arteriovenous fistula was confirmed by arteriography. A balloon-expandable stent graft was placed across the arteriovenous fistula in the superior mesenteric artery. Postprocedure, the patient's abdominal pain resolved and his bilirubin decreased from 2.9 to 0.4. Endovascular repair of a superior mesenteric to portal arteriovenous fistula utilizing a stent graft is feasible and minimally invasive.

Delayed development of a traumatic superior mesenteric arteriovenous fistula following multiple gunshot wounds to the abdomen.

Traumatic visceral arteriovenous fistulae are rare and pose a diagnostic and therapeutic challenge. We present the case of a 20-year-old male who sustained multiple gunshot wounds to the abdomen, injuring the inferior vena cava, duodenum, stomach, and small bowel. The patient was taken emergently to the operating room for repair of his injuries, which required primary small bowel repair, duodenal repair, and inferior vena cava ligation due to exigent hemorrhage. At the initial operation there was a normal pulse in the superior mesenteric artery at the base of the small bowel mesentery, with no evidence of hematoma or thrill in the small bowel mesentery. The patient was subsequently returned to the operating room several times for bowel exploration and abdominal wall closure with mesh. Ten days after his initial injury, the patient was noted to have an abdominal bruit on physical exam. Arteriography demonstrated a fistula between the proximal superior mesenteric artery and vein with significant portal hypertension. The patient underwent surgical repair of the superior mesenteric artery and vein with closure of the fistula. The patient had no further complications and was discharged from the hospital 1 month later, after abdominal wall skin grafting, in good condition. The patient remains in good health 12 months later. Continued vigilance and careful physical examination are important in the identification of delayed vascular injuries and allow timely treatment and avoidance of untoward long-term sequelae.

Inflammatory abdominal aortic aneurysm treated by endovascular stent grafting: a case report.

Despite complications inherent to open surgical repair of inflammatory abdominal aortic aneurysms, there is expected resolution of the retroperitoneal inflammatory process following graft replacement. An endovascular approach could also exclude the aneurysm while potentially avoiding injury to vital structures in the hostile operative field. However, data are limited regarding the role of endovascular stent grafts in the management of inflammatory abdominal aortic aneurysms. Furthermore, postoperative regression of perianeurysmal inflammation is rarely discussed in the few published accounts of endovascular repair of inflammatory aortic aneurysms. The case presented demonstrates successful endovascular treatment of an infrarenal inflammatory aneurysm with resolution of the retroperitoneal inflammation and hydronephrosis.

Lung cancer in patients younger than 40 years of age.

BACKGROUND AND OBJECTIVES: We investigated whether the clinicopathologic characteristics and prognosis of lung cancer in younger patients differ from those of older patients. METHODS: Among 2,763 lung cancer patients treated during the period from April of 1972 to April of 1997, we retrospectively investigated the clinical features and prognosis of 53 patients under 40 years of age (young group) and compared them with the findings of 1,886 patients with 60 years of age or older (elderly group). RESULTS: The proportion of female patients in the younger group was significantly higher than that in the elderly group (39.6% vs. 24.1%). The young group had a significantly higher proportion of adenocarcinoma (75.5% vs. 44.8%) and stage III-IV disease (73.6% vs. 59.2%) and a significantly lower proportion of squamous cell carcinoma (3.8% vs. 32.1%). Regarding the selection of therapy, in the young group, a significantly lower proportion of patients underwent surgical therapy (35.8% vs. 41.5%) and a significantly higher proportion of those (37.7% vs. 16.4%) received chemotherapy. The overall survival between the young and elderly groups was not significantly different. Moreover, the 5-year survival rate of the patients undergoing a surgical resection was 56.1% in the young group and 44.8% in the elderly group (P = 0.0615). CONCLUSIONS: This study suggests that the prognosis of young patients with lung cancer is at least equivalent to that of older patients; therefore, they should be managed according to the general therapeutic guidelines.

Surgical treatment of a sigmoid volvulus associated with megacolon: report of a case.

Sigmoid volvulus occurring concomitantly with megacolon is an uncommon cause of bowel obstruction, and various approaches to treatment have been proposed. We report herein a case of sigmoid volvulus with megacolon that was successfully treated by elective surgery following endoscopic reduction during the same hospital stay. A 70-year-old woman was admitted to our hospital with abdominal pain, distension, and severe constipation. Physical examination, plain abdominal X-ray, and barium enema confirmed a sigmoid volvulus and further examinations revealed concomitant megacolon. An elective sigmoid colectomy was performed following successful endoscopic decompression. The postoperative course was uneventful and there was no residual colonic dysmotility. Histologically, no aganglionic tissue was observed in the resected specimen.

Primary healing of physeal separation under rigid fixation.

We observed the healing process under rigid external fixation after Salter-Harris type-1 or type-2 physeal separation at the proximal tibia in immature rabbits. Metaphyseal vessels grew across the gap with little delay; the site of separation then came to lie in the metaphysis and was bridged by endochondral ossification. Union was achieved within two days in all rabbits. Progression of endochondral ossification repaired the separated physis, thus showing 'primary healing of physeal separation'. This depends on accurate reduction and stable fixation to allow the survival of vessels across the gap.