Clinical role of serum programmed death ligand 1 in patients with hepatocellular carcinoma: Where does it come from?

Programmed death ligand 1 (PD-L1) is a key target for the treatment of several malignancies. The present study was conducted to clarify the role of serum PD-L1 in hepatocellular carcinoma (HCC). Serum PD-L1 (sPD-L1) was examined by an enzyme-linked immunosorbent assay in 153 patients with HCC who underwent curative hepatectomy at Kumamoto University in 2011–2016. The expression of PD-L1 in tissue (tPD-L1) was investigated by immunohistochemistry. The clinical roles of the PD-L1 expression in both serum and tissue were examined. The sPD-L1 was significantly elevated in HCC patients compared to patients without any malignant or inflammatory disease (234 vs. 93 pg/mL, p < 0.0001). The percentage of the tPD-L1-positive area (%tPD-L1) in the background liver was significantly higher than in the tumor (1.52% vs. 0.48%, p < 0.0001). The %tPD-L1 in the background liver but not in the tumor was significantly correlated with the sPD-L1 level (p = 0.0079). The sPD-L1, %tPD-L1 in the tumor, and %tPD-L1 in the background liver were not correlated with the overall survival after surgery. PD-L1-expressing cells in the background liver, but not in the tumor tissue, appeared to contribute to the sPD-L1 level. The sPD-L1 level may thus not indicate the tumor burden in patients with HCC.     

Multiple excimer laser phototherapeutic keratectomies for Avellino corneal dystrophy: a case report

Dear Editor,I am Chihiro Koiwa,from the Department of Ophthalmology,Juntendo University Hospital.I am writing this letter to present a case of multiple excimer laser phototherapeutic keratectomies(PTKs)for Avellino corneal dystrophy(ACD).Corneal dystrophy is a common type of hereditary,noninflammatory,and bilateral corneal disorder that involves various pathological,histological,and clinical manifestations[1].Advanced molecular gene sequencing has identified specific mutations that are associated with most dystrophies of this type.ACD,also known as granular corneal dystrophy typeⅡ[2],is autosomal dominant and associated with the R124H mutation of the transforming growth factor beta-induced(TGFBI)gene and characterized by deposits consistent with both discrete granular and lattice corneal opacities[3-4].An analysis of the TGFBI gene is essential to differentiate ACD because heterozygous R124H mutation carriers have minimal corneal abnormalities,whereas homozygotes have severe visual impairment,starting from early childhood,and early postoperative recurrence of corneal opacity.     

Effect of natural extract eye drops in dry eye disease rats

AIM: To reveal a novel MITF gene mutation in Waardenburg syndrome (WS), which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes, hair and skin. METHODS: The genetic analysis of the Chinese family was conducted by whole-exome sequencing, then the results were confirmed by Sanger sequencing. RESULTS: WS is classified into type I to IV, which are identified by the W index, clinical characteristics and additional features. The MITF gene mostly accounts for WS type II. In this study, a de novo heterozygous mutation in the MITF gene, c.638A>G in exon 7, was identified in the patient diagnosed with WS type I features, as the W index was 2.17 (over 2.10), with dystrophia canthorum, congenital bilateral profound hearing loss, bilateral heterochromia irides, premature greying of the hair, and excessive freckling on the face at birth. She also underwent refractive errors and esotropia, reduced pigmentation of the choroid and visible choroid vessels. The mutation was not found in previous studies or mutation databases. CONCLUSION: The novel mutation in the MITF gene, which altered the protein in amino acids 213 from the glutamic acid to glycine, is the genetic pathological cause for WS features in the patient. Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS, which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities. Moreover, ocular symptoms should be emphasized in all types of WS patients.     

Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese

Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP‐induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty‐eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age‐matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1217–1226, 2014.