Skeletal characteristics and treatment outcome of five patients with Robin sequence

OBJECTIVE: To examine the variation in the precise skeletal characteristics and the treatment outcomes of five Japanese Robin sequence cases. MATERIALS AND METHODS: The birth histories and orthodontic records of five Japanese Robin sequence patients were collected and analyzed. RESULTS: All cases had a retrognathic appearance with small SNA and SNB angles. They had significantly steep mandibular planes with lingual tipped incisors in both arches. The gonial angles in two cases were within the Japanese norm, whereas the remaining three showed significantly enlarged angles. Moreover, all cases showed a significantly shorter ramus length, but the mandibular body was short in only two cases. All had moderate or severe crowding in both arches, and therefore extraction of lateral dentition or lateral incisors was performed in conjunction with orthodontic treatment. An edgewise multibracket appliance was placed, and labial tipping of the lower incisors was performed in all cases. All obtained normal functional occlusion after active treatment, but the retrognathic appearance remained in most cases. CONCLUSIONS: The present cases with Robin sequence showed variation in the gonial angle and mandibular body length, although all commonly exhibited smaller SNA and SNB angles with significantly steep mandibular planes. Significant labial tipping of the lower incisors was required during the active treatment, and all cases finally obtained functional occlusion, indicating the relatively good prognosis on the occlusion of this sequence.     

Inhibition of hepatitis C virus NS3 helicase by manoalide

The hepatitis C virus (HCV) causes one of the most prevalent chronic infectious diseases in the world, hepatitis C, which ultimately develops into liver cancer through cirrhosis. The NS3 protein of HCV possesses nucleoside triphosphatase (NTPase) and RNA helicase activities. As both activities are essential for viral replication, NS3 is proposed as an ideal target for antiviral drug development. In this study, we identified manoalide (1) from marine sponge extracts as an RNA helicase inhibitor using a high-throughput screening photoinduced electron transfer (PET) system that we previously developed. Compound 1 inhibits the RNA helicase and ATPase activities of NS3 in a dose-dependent manner, with IC(50) values of 15 and 70 μM, respectively. Biochemical kinetic analysis demonstrated that 1 does not affect the apparent K(m) value (0.31 mM) of NS3 ATPase activity, suggesting that 1 acts as a noncompetitive inhibitor. The binding of NS3 to single-stranded RNA was inhibited by 1. Manoalide (1) also has the ability to inhibit the ATPase activity of human DHX36/RHAU, a putative RNA helicase. Taken together, we conclude that 1 inhibits the ATPase, RNA binding, and helicase activities of NS3 by targeting the helicase core domain conserved in both HCV NS3 and DHX36/RHAU.     

Laminin-5 immunohistochemical mapping for analysis of local extension in hypopharyngeal cancer: A preliminary report

Objective

Laminin-5 γ2 chain (LNγ2) plays an important role in cancer differentiation and migration. Using a novel immunohistochemical mapping technique to investigate whole mucosal strips of total laryngopharyngectomy specimens using iodine, H–E, and LNγ2 stainings, we investigated the locoregional behavior of hypopharyngeal cancer.

Methods

Surgical specimens from two patients with pyriform sinus cancer were investigated. Three percent iodine was applied to the tumor-bearing laryngopharynx during surgery and photographed. Stainabilities of H–E and LNγ2 on pathologic sections from all mucosal strips were scored and coordinated with the laryngopharyngeal photograph to illustrate the immunohistochemical map.

Results

In both patients, the main tumor of invasive squamous cell carcinoma was circumferentially surrounded by a superficial lesion characterized by high grade intraepithelial neoplasia that remained unstained by iodine. On LNγ2 immunohistochemical mapping, the main tumor was demonstrated by Score 2 staining and the superficial lesion by a stronger Score 3 staining.

Conclusions

The finding of neoplastic cells at the periphery demonstrating a higher potential than the cancer cells at the tumor center is suggestive of impending progression from neoplasia to carcinoma. The current preliminary report suggested morphological evidence of intraepithelial infiltration and lateral invasion in hypopharyngeal cancer.     

Nasal splinting using silicone plates without gauze packing following septoplasty combined with inferior turbinate surgery

Objective

Nasal packing after septoplasty is uncomfortable and painful for patients. The aim of this study was to determine the efficacy of nasal splinting using silicone plates to prevent complications and decrease the pain after septoplasty compared with the conventional gauze packing.

Materials and methods

Thirty-five adult patients who had undergone septoplasty were included in this study. The patients were allocated into two groups: Group S, silicone plates were used (13 males, 2 females); and Group G, gauze packing smeared with an antibiotic ointment was used (19 males, 1 female). We evaluated and compared the postoperative pain, pain due to postoperative cleaning, nasal bleeding, postnasal drip, body temperature, effect on stay in the hospital, effect on food intake and sleep disturbance using visual analogue scale (VAS) scores.

Results

The postoperative pain score in Group S was significantly lower than in Group G on days 1 and 2 after the septoplasty. And the pain due to postoperative cleaning score was significantly lower than in Group G on days 2 and 3 after operation. No statistically significant differences were found between the two groups in regard to nasal bleeding, postnasal drip, body temperature, effect on stay in the hospital, effect on food intake or sleep disturbance. Objective evaluation performed at 4 weeks postoperatively revealed that nasal crusting occurred at a significantly higher incidence in Group G compared with Group S.

Conclusion

The use of silicone plates in lieu of conventional gauze packing decreased post-septoplasty nasal pain and pain due to postoperative cleaning of the nasal cavity. We conclude that nasal splinting using silicone plates after septoplasty is an effective method for managing pain and preventing complications.     

Complete clinical and pathological response to mFOLFOX6 neoadjuvant chemotherapy in a case of advanced rectal cancer

The patient was a 78-year-old woman with a chief complaint of abdominal bloating and constipation who was referred to us and was examined for an AV 12-15 cm, circumferential type 2 rectal cancer. The pathological diagnosis was adenocarcinoma (tub1+tub2). T4 and N2 were suspected based on the CT findings, and because the CEA value was high, the patient was treated with 7 courses of mFOLFOX6 neoadjuvant chemotherapy followed by salvage surgery(low anterior resection+D3). Examination of the surgical specimen revealed chronic inflammatory cell infiltration, including histiocytes accompanied by ulceration, and fibrosis was observed down to SS. No viable cancer cells were detected, and the tumor response was evaluated as a pathological CR. mFOLFOX6 appeared to be effective as neoadjuvant chemotherapy for advanced rectal cancer.     

Attempted suicide of youth with Asperger's disorder]

Research of Asperger's disorder is increasing through strong interest in this disorder. However, there are few reports on suicide attempts among youths with this disorder. We examined the clinical characteristics of serious suicide attempts of adolescents, and indicated the frequency of pervasive developmental disorders among them. In the present study, we reported a suicide attempt using briquettes by a youth with Asperger's disorder aged 23, who had a history of two suicide attempts by hanging. In this case, we examined the predisposing factors to suicide and possible intervention to prevent a re-attempt. As a result, in this case, we suggested that low self-esteem due to repeated serious social failures and feelings of isolation, although there was a social support system, were psycho-social predisposing factors. Moreover, the "conflict" between the patient and his parents, who should have provided social support for him, had made him feel alone. This "conflict" was composed of 1) the primary symptoms of Asperger's disorder (deficit of emotional reciprocity and unreasonable insistence on restricted thoughts.) and 2) his parents' insufficient comprehension of Asperger's disorder. This "conflict" was distinct from the conflict of interpersonal friction based on emotional interaction. In order to prevent a suicide re-attempt, we mainly intervened in the problem of low self-esteem due to repeated serious social failures and having feelings of isolation. We concluded that to prevent a suicide re-attempt in patients with Asperger's disorder, it is important to diagnose and treat the disorder and comorbidity, and it is more important to recognize and aggressively intervene in psycho-social predisposing factors.     

Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers

Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p < 0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p = 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined.     

Novel NBS1 heterozygous germ line mutation causing MRE11-binding domain loss predisposes to common types of cancer

DNA damage response (DDR) pathways maintain genomic stability. A 657del5 mutation of NBS1, a key DDR component, causing the rare cancer-predisposing Nijmegen breakage syndrome has been reported nearly exclusively in Slavic populations. In this study, we describe the first identification in a Japanese population of an unprecedented type of heterozygous NBS1 mutant, termed IVS11+2insT, lacking the MRE11- and ATM-binding site at the COOH terminus. Profoundly defective in crucial binding to MRE11, MDC1, BRCA1, and wild-type NBS1, the mutant caused impaired ATM phosphorylation in response to low-dose irradiation in a heterozygous state. Importantly, whereas IVS11+2insT was found in only 2 (0.09%) of 2,348 control subjects, it was identified in 2% (2 of 96) of heterozygotes with gastric cancer, 0.8% (3 of 376) of those with colorectal cancer, and 0.4% (2 of 532) of those with lung cancer, which were comparable to frequencies reported for other DDR-related genes known to confer cancer susceptibility. The presence of the heterozygous IVS11+2insT mutation seemed to be associated with an increased risk for gastrointestinal cancers, with an odds ratio of 12.6 and 95% confidence interval (95% CI) of 2.05 to 132.1 (P = 0.0001). The odds ratios separately calculated for gastric and colorectal cancers were 25.0 (95% CI, 1.78-346.0) and 9.43 (95% CI, 1.08-113.1), respectively. These findings suggest that IVS11+2insT is associated with an increased risk for the development of certain types of common cancers, warranting future investigation including detailed phenotypic characterization of age of onset and penetrance in heterozygotes, as well as screening in other ethnic groups.