Clinical and histopathological study of Charcot-Marie-Tooth neuropathy with a novel S90W mutation in BSCL2

The objective of the study was to investigate the disease-causing mutation in an autosomal dominant Charcot-Marie-Tooth disease type 2 family and examine the clinical and histopathological evaluation. We enrolled a family of Korean origin with axonal Charcot-Marie-Tooth disease neuropathy (FC305; 13 males, six females) and applied genome-wide linkage analysis. Whole exome sequencing was performed for two patients. In addition, sural nerve biopsies were obtained from two patients. Through whole exome sequencing, we identified an average of 20,336 coding variants from two patients. We also found evidence of linkage mapped to chromosome 11p11-11q13.3 (LOD score of 3.6). Among these variants in the linkage region, we detected a novel p.S90W mutation in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene, after filtering 31 Korean control exomes. Our p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and predominant right thenar muscle atrophy in comparison with reported p.S90L patients. The phenotypic spectra were wide and demonstrated intrafamilial variability. Two patients with different clinical features underwent sural nerve biopsies; the myelinated fiber densities were increased slightly in both patients, which differed from two previous case reports of BSCL2 mutations (p.S90L and p.N88S). This report expands the variability of the clinical spectrum associated with the BSCL2 gene and describes the first family with the p.S90W mutation.     

A Case of Paclitaxel-induced Maculopathy Treated with Methazolamide

A 54-year-old female patient who had been undergoing anti-cancer chemotherapy and radiotherapy for seven years after surgery for left breast cancer visited our clinic for visual disturbance in the right eye at nine months after paclitaxel administration. The best-corrected visual acuity was 0.5 in the right eye and 1.0 in the left eye. The patient was diagnosed with maculopathy due to paclitaxel administration based on the finding of cystoid macular edema in the right eye on fundus examination and optical coherence tomography; however, no leakage was detected on fluorescein angiography. Thus, drug replacement was planned. On the other hand, no abnormal finding was observed in the left eye. However, as the anti-cancer effect of paclitaxel is significant, replacing paclitaxel with another agent was not warranted; therefore, maintenance therapy with methazolamide was performed before and after administering the anti-cancer agent. Aggravation of cystoid macular edema was prevented, and vision improvement was achieved by oral maintenance therapy with methazolamide. In addition, the same fundus findings as shown in the right eye were detected in the left eye at 16 months after paclitaxel administration. After administering methazolamide, macular thickness was reduced, and vision was improved in the left eye. Paclitaxel administration was discontinued due to cutaneous metastasis from the breast cancer, and another anti-cancer agent was then administered. No subsequent cystoid macular edema has occurred.     

Elucidation of molecular expression associated with abnormal development and sterility caused by electron beam irradiation in Spodoptera litura (F.) (Lepidoptera: Noctuidae)

Abstract

Purpose: The objective of the present study was to elucidate the mode of indirect action of electron beam irradiation at the molecular level against a quarantine pest, Spodoptera litura (F.).

Material and methods: Electron beam irradiation (50–200?Gy) was applied to S. litura eggs, larvae, pupae, and adults, after which the feeding area, body weight, deformity of pupae and adults, ovarian development, expression levels of vitellogenin (Vg) and vitellogenin receptor (VgR) genes, and protein levels were analyzed.

Results: The amount of feeding by S. litura larvae and the synthesis level of 70?kDa storage protein significantly decreased as the electron beam dose increased. When larvae were treated with the electron beam, morphological deformities appeared in the pupae, and abnormal wing disc (AWD) expression significantly decreased. Ovarian development was completely inhibited in emerged adults that had undergone 200?Gy electron beam irradiation as pupae. Quantitative real-time PCR (qRT-PCR) assays showed significant downregulation of the Vg and VgR genes due to electron beam irradiation; whereas the synthesis level of Vg protein (190?kDa) did not decrease with time in eggs unlike in non-irradiated (control) S. litura eggs, exhibiting irradiation induced impairment of Vg functioning.

Conclusions: These findings of radiation-induced abnormal development and sterility in S. litura together with the correlated changes at the molecular level may facilitate the development of a phytosanitary strategy against this quarantine pest using electron beam irradiation.     

Differences in autophagy-related activity by molecular subtype in triple-negative breast cancer

The aim of this study was to assess the expression of significant components of autophagy including beclin-1, light chain (LC) 3A, LC3B, and p62 in the molecular subtypes of triple-negative breast cancer (TNBC) and to evaluate the implications of the results. Tissues from 119 cases of TNBC were used for a tissue microarray. Expression of cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), claudin 3, claudin 4, claudin7, E-cadherin, androgen receptor (AR), and gamma-glutamyltransferase 1 (GGT-1) was detected by immunohistochemical staining of the tissue microarrays. According to the results, the 119 cases of TNBC were subclassified into basal-like type (CK5/6-positive and/or EGFR-positive group), molecular apocrine type (AR-positive and/or GGT-1-positive group), claudin low type (claudin 3-, claudin 4-, or claudin 7-negative and/or E-cadherin-negative group), mixed type (having the features of more than two types), or null type (none of the above). Immunohistochemical staining for autophagy-related markers including beclin-1, LC3A, LC3B, and p62 was performed to evaluate the difference between clinicopathological parameters. TNBCs were categorized as basal-like type (36 patients, 30.3?%), molecular apocrine type (8 patients, 6.7?%), claudin low type (16 patients, 13.4?%), mixed type (37 patients, 31.1?%), and null type (22 patients, 18.5?%). Expression of nuclear p62 was higher in the molecular apocrine type and claudin low type than in other types of TNBC (p?=?0.008). Expression of beclin-1 was higher in molecular apocrine type than in other TNBC types (p?=?0.039). Expression of LC3A and LC3B showed no difference between the molecular subtypes. Multivariate Cox analysis revealed that the negative expression of p62 was associated with shorter disease-free survival [p?=?0.012; odds ratio, 3.192; 95?% confidence interval (CI), 1.293?C7.882] and shorter overall survival (p?=?0.009; odds ratio, 3.895; 95?% CI, 1.409?C10.771). Among the subtypes of TNBC, molecular apocrine breast cancer showed a higher expression of nuclear p62 and beclin-1 than others, which reflected higher autophagy activity.     

Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 2: Alcohol-Associated Osteonecrosis

Background

Although alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH) and its prevalence reportedly ranges from 20% to 45%, there are no unified classification criteria for this subpopulation. In 2015, Association Research Circulation Osseous decided to develop classification criteria for alcohol-associated ONFH.

Individualized optimal surgical extent of the lateral neck in papillary thyroid cancer with lateral cervical metastasis

Despite an excellent prognosis, cervical lymph node (LN) metastases are common in patients with papillary thyroid cancer (PTC). The presence of metastasis is associated with an increased risk of locoregional recurrence, which significantly impairs quality of life and may decrease survival. Therefore, it has been an important determinant of the extent of lateral LN dissection in the initial treatment of PTC patients with lateral cervical metastasis. However, the optimal extent of therapeutic lateral neck dissection (ND) remains controversial. Optimizing the surgical extent of LN dissection is fundamental for balancing the surgical morbidity and oncological benefits of ND in PTC patients with lateral neck metastasis. We reviewed the currently available literature regarding the optimal extent of lateral LN dissection in PTC patients with lateral neck metastasis. Even in cases with suspicion of metastatic LN at the single lateral level or isolated metastatic lateral LN, the application of ND including all sublevels from IIa and IIb to Va and Vb may be overtreatment, due to the surgical morbidity. When there is no suspicion of LN metastasis at levels II and V, or when multilevel aggressive neck metastasis is not found, sublevel IIb and Va dissection may not be necessary in PTC patients with lateral neck metastasis. Thus consideration of the individualized optimal surgical extent of lateral ND is important when treating PTC patients with lateral cervical metastasis.