Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.     

Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle–related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.     

Hybrid approach with laparoscopic wall-inversion surgery and single-incision intragastric surgery for intraluminal gastrointestinal stromal tumor: A case report

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full-thickness partial resection using a hybrid approach of laparoscopic surgery and single-incision intragastric surgery (SIIGS). A 69-year-old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall-inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall-inversion surgery by removing size limitations.     

Debate on MERS-CoV respiratory precautions: surgical mask or N95 respirators?

Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in mid-2012, there has been controversy over the respiratory precaution recommendations in different guidelines from various international bodies. Our understanding of MERS-CoV is still evolving. Current recommendations on infection control practices are heavily influenced by the lessons learnt from severe acute respiratory syndrome. A debate on respiratory precautions for MERS-CoV was organised by Infection Control Association (Singapore) and the Society of Infectious Disease (Singapore). We herein discuss and present the evidence for surgical masks for the protection of healthcare workers from MERS-CoV.     

Nifedipine induces gingival epithelial hyperplasia in rats through inhibition of apoptosis

BACKGROUND: Nifedipine is used as a long-acting vasodilator; one of its side effects is gingival overgrowth, characterized by an accumulation of collagenous components within the gingival connective tissue and epithelial hyperplasia with elongated, branched rete pegs penetrating into the connective tissue. We investigated the effect of nifedipine on apoptosis of gingival keratinocytes of rats to elucidate the mechanism of nifedipine-induced gingival epithelial hyperplasia. METHODS: Twenty-day-old rats were fed a powdered diet containing or lacking nifedipine for 8 to 30 days. The mandibular gingiva and palatal mucosa were removed on days 8, 15, or 30, and epithelial thickness was examined by light microscopy. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to examine apoptosis of keratinocytes in the epithelium. In addition, we examined the effects of nifedipine on proliferation of keratinocytes and epithelial cell life on day 8 by 5-bromo-2'-deoxyuridine (BrdU) staining. RESULTS: Microscopic examination showed gingival epithelial hyperplasia in nifedipine-treated rats after day 15. Apoptosis of gingival keratinocytes was seen to be inhibited in nifedipine-treated rats on day 8 and 15. Also, nifedipine did not induce an increase of keratinocyte proliferation activity in terms of the number of cells showing positive staining with BrdU. Prolongation of cell life by nifedipine was observed on day 8 in gingival epithelium through a delay of upward cell movement compared to controls. However, epithelial hyperplasia was not detected in palatal mucosa, and there were no significant differences in apoptotic rates of keratinocytes and cell life between nifedipine-treated rats and control rats. CONCLUSIONS: These results suggest that nifedipine induces epithelial hyperplasia in gingival overgrowth not by an increase in keratinocyte proliferation, but by prolongation of cell life through reduction of apoptosis before epithelial hyperplasia is detectable.     

Topical administration of simvastatin recovers alveolar bone loss in rats

Background and Objective:  Simvastatin, a cholesterol-lowering drug, has been reported to show anabolic effects on bone metabolism. We examined the effects of simvastatin in vitro using cultured rat calvaria cells and in vivo using periodontitis-induced rats.
Material and Methods:  Alkaline phosphatase activity and bone nodule formation were measured in cultured rat calvaria cells. Nylon ligature was placed around the maxillary molars of Fischer male rats for 20 d to induce alveolar bone resorption. After ligature removal, simvastatin was topically injected into the buccal gingivae for 70 d and then microcomputed tomography and histological examinations were performed.
Results:  Simvastatin maintained high alkaline phosphatase activity and increased bone nodule formation in rat calvaria cells in a dose-dependent manner, showing that simvastatin increased and maintained a high level of osteoblastic function. Microcomputed tomography images revealed that treatment with simvastatin recovered the ligature-induced alveolar bone resorption, showing a 46% reversal of bone height. Histological examination clarified that low-mineralized alveolar bone was formed in simvastatin-treated rats.
Conclusion:  These findings demonstrate that simvastatin has the potential to stimulate osteoblastic function and that topical administration of simvastatin may be effective for the recovery of alveolar bone loss in rats.     

Backward distraction osteogenesis of condylar segment in patient with mandibular ramus deficiency--report of a case

A backward distraction osteogenesis (BDO) of the condylar segment for treatment of mandibular ramus deficiency was developed. This report describes the clinical progress of a patient with mandibular ramus deficiency in whom satisfactory occlusion was achieved and maintained by gradual posterosuperior repositioning of the displaced condyles into the glenoid fossae during intermaxillary fixation. Findings of pre- and postoperative clinical and magnetic resonance imaging indicate that the effect of BDO on the temporomandibular joint was negligible.     

Topical and intermittent application of parathyroid hormone recovers alveolar bone loss in rat experimental periodontitis

Tokunaga K, Seto H, Ohba H, Mihara C, Hama H, Horibe M, Yoneda S, Nagata T. Topical and intermittent application of parathyroid hormone recovers alveolar bone loss in rat experimental periodontitis. J Periodont Res 2011; 46: 655–662. © 2011 John Wiley & Sons A/S Background and Objective: Periodontitis is characterized by periodontal tissue inflammation and alveolar bone loss. The intermittent administration of parathyroid hormone (PTH), a major regulator of bone remodeling, has been demonstrated to stimulate osteoblastic activity. Although the systemic administration of PTH has been reported to protect against periodontitis‐associated bone loss, the effect of the topical administration of PTH is unclear. In this study, the effect of intermittent administration of PTH on osteoblastic differentiation was examined in cultured calvaria cells and then the effect of topical and intermittent administration of PTH was determined by measuring the recovery of alveolar bone loss after inducing experimental periodontitis in rats. Material and Methods: Alkaline phosphatase activity and bone nodule formation were measured in fetal rat calvaria cells. Experimental periodontitis was induced by placing nylon ligature around rat maxillary molars for 20 d. After ligature removal (day 0), PTH was topically injected into buccal gingiva three times a week for 10 wk. Micro‐computed tomography analysis and histological examination were performed on days 35 and 70. Results: Intermittent exposure of PTH in calvaria cells increased alkaline phosphatase activity and bone nodule formation by 1.4‐ and 2.4‐fold, respectively. Ligature procedures induced marked alveolar bone loss around the molars on day 0 and greater bone recovery was observed in the PTH‐treated rats on day 70. An increase in osteoid formation on the surface of alveolar bone was detected in the PTH‐treated rats. Conclusion: Intermittent treatment with PTH stimulated osteoblastic differentiation in fetal rat calvaria cell cultures, and topical and intermittent administration of PTH recovered alveolar bone loss in rat experimental periodontitis.     

Butyric acid induces apoptosis in inflamed fibroblasts

Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine and human T- and B-cells, whereas intact gingival fibroblasts isolated from healthy humans are resistant to butyric-acid-induced apoptosis. We examined the susceptibility of inflamed gingival fibroblasts isolated from adult persons with periodontitis to butyric-acid-induced apoptosis. Butyric acid significantly suppressed the viability of inflamed gingival fibroblasts and induced apoptosis in a dose-dependent manner. The incubation of inflamed gingival fibroblasts with butyric acid induced DNA fragmentation and apoptotic changes such as chromatin condensation, hypodiploid nuclei, and mitochondrial injury. Furthermore, butyric-acid-induced apoptosis in inflamed gingival fibroblasts was reduced by caspase-3/7, -6, -8, and -9 inhibitors. Thus, inflamed gingival fibroblasts from adult persons with periodontitis appear to be highly susceptible to mitochondria- and caspase-dependent apoptosis induced by butyric acid, compared with healthy gingival fibroblasts.