Ophthalmic Features in Prader-Willi Syndrome Patients with Type-2 Diabetes Mellitus

Purpose：To investigate and compare features of diabetic retinopathy（DR）in patients with Prader-Willi Syndrome（PWS）and those without PWS.Methods：Overall, 33 PWS patients with type-2 diabetes mellitus（T2DM）secondary to PWS（65 eyes） and 55 age-matched patients with T2DM（109 eyes）without congenital heredity diseases were reviewed. Medical records of 65 eyes with PWS（PWS group：mean age 24.7±5.9 years）and 109 eyes without PWS （control group：mean age 22.9±6.2 years）were acquired and compared from January 2000 to November 2018. Best-corrected visual acuity（BCVA）was determined and DR scores were assigned.Results：BCVA was significantly low in PWS group compared with the controls（P＜0.001）. Pseudophakia was frequently observed in patients in the PWS group（P＝0.024）. No significant differences were found with respect to cataract（P＝0.065）and DR score（P＝0.77）between patients in the PWS and control groups. Investigations into the possible causes of the low BCVA in the PWS group found no significant difference regarding strabismus（P＝0.065）. However, significant differences were found between both groups with respect to amblyopia（P＜0.01）. Visual acuity examinations were incomplete in some patients with PWS because of their inability to concentrate（P＜0.01）.Conclusions：There was no correlation between DR progression and PWS. Lower BCVA in PWS patients was likely owing to amblyopia and incomplete visual acuity examination owing to inability of patients with PWS to concentrate

Induction of embryonal carcinoma cell differentiation by deferoxamine, a potent therapeutic iron chelator

AbstractWe investigated the effects of deferoxamine on the differentiation of embryonal carcinoma F9 cells. Deferoxamine, a widely used therapeutic agent for thalassemia and iron overload, was found to induce F9 cell differentiation and to have some unique characteristics compared with other chelators, hinokitiol and dithizone, which were previously reported to induce differentiation of these cells. This hydrophilic agent induced reversible differentiation as did sodium butyrate, whereas other chelators did not. However, morphological features of the cells after deferoxamine-induced differentiation were similar to those of cells incubated with the other chelators. The differentiation-inducing activity of deferoxamine was abolished by preincubation with Fe3+ ions, similarly to the other chelators examined. Moreover, cell proliferation was inhibited by treatment with this agent, and the numbers of cells in the colonies were reduced by apoptosis. Based on these results, we conclude that deferoxamine induces differentiation and apoptosis of F9 cells via chelation of extracellular and/or intracellular Fe3+ ions

Duodenal Gastrointestinal Stromal Tumor Treated by Wedge Resection in a Patient with Neurofibromatosis Type 1: Report of a Case and Review of the Japanese Literature

A case of duodenal gastrointestinal stromal tumor (GIST) treated by wedge resection in a patient with neurofibromatosis type 1 (NF-1) is reported. A 55-year-old man with a history of NF-1 was admitted for surgery for a duodenal tumor. Upper gastrointestinal endoscopy revealed a 2.5 cm duodenal submucosal tumor. Abdominal computed tomography showed a homogenously enhanced mass in the third portion of the duodenum. The patient successfully underwent wedge resection of the duodenal tumor. Histological examination revealed proliferation of spindle tumor cells arranged in a bundle pattern. This tumor was immunohistochemically positive for c-Kit and CD34, and negative for S-100 and α-SMA. A mitotic count showed 3 mitoses per 50 high-power fields. The tumor was diagnosed as a low-risk GIST. The patient's postoperative course was uneventful. GIST in a patient with NF-1 is rare, only 27 cases being reported in the Japanese literature

Pre- and Postoperative Ocular Events in Cataract Patients with Small Pupils who Underwent Cataract Surgery

Purpose：To analyze pre- and postoperative surgical events in cataract patients with small pupils who underwent cataract surgery.Patients and methods：We reviewed the medical records of patients who underwent cataract surgery between January 2009 and May 2014 at Dokkyo Medical University Koshigaya Hospital. Surgery was performed by four experienced surgeons. We included 106 eyes from 83 patients with pupil sizes ＜5 mm in diameter who required iris retractors during the cataract surgery （small pupil group）. The control group was comprised of 447 eyes from 319 patients with pupil sizes ＞5 mm in diameter who did not require a mechanical dilatation of the pupil during cataract surgery. Pre- and postoperative intra- or extraocular surgical events were analyzed.Results：Preoperative intra- or extraocular surgical events were observed in 36 eyes （34.0％） in the small pupil group and 72 eyes （16.1％） in the control group, with a significant difference observed for those who underwent laser iridotomy （P＜0.001） and trabeclectomy （P＜0.01）. Postoperative intra- or extraocular events were observed in 25 eyes （23.6％） in the small pupil group and 61 eyes （13.7％） in the control group, with significant differences observed for those who underwent the following procedures：trabeculectomy （P＜0.001）, sub-Tenon’s injection of triamcinolone acetonide （P＜0.001）, and posterior capsulotomy （P＝0.012）.Conclusion：Cataract patients with small pupils often have pre- and postoperative intra- or extraocular surgical events. It should be recognized that cataract surgery is only one step in the treatment of cataract patients with small pupils

<CLINICAL REPORT>A case of inverted papilloma of the maxillary sinus

A case of inverted papilloma arising in the maxillary sinus is described. The first symptoms were rhinorroea and discomfort of the left infraorbital region. A biopsy obtained by penetration into the maxillary sinus resulted in a diagnosis of chronic sinusitis. However, the surgical specimen showed characteristic inverted epithelial proliferation. Two years after operation by the Caldwell-Luc method, there are no signs of recurrence. The diagnosis and treatment of inverted papilloma are discussed

Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Corneal Perforation Associated with the Oral Anticancer Drug S-1：A Case Report

Purpose：S-1 is an oral anticancer drug containing tegafur, a prodrug of 5-fluorouracil（5-FU）. We present a patient who experienced corneal perforation that appeared to be caused by S-1 administration．Case：A 67-year-old woman was presented to our hospital because of corneal perforation in her left eye. She had been administrated S-1 for 17 months from gastroenterological surgeon at another hospital for treating pancreatic cancer. The best-corrected visual acuity was 0.4 in the right eye and 0.1 in the left eye at the initial visit. Convoluted subepithelial opacity was present in the cornea of the right eye, and corneal perforation was observed in the left eye. Anterior chamber formation was very poor, and iris incarceration was present in the left eye. Although anterior chamber formation was attempted with the use of soft contact lens wear, the condition remained unchanged. We requested to discontinue S-1 administration to gastroenterological surgery at another hospital. The patient was presented to the department of ophthalmology at another hospital because her eye condition and pancreatic cancer could be treated at the same institution.Conclusion：Patients treated with S-1 should be carefully followed up for ocular complications because corneal perforation may occur

Phthiriasis Palpebrarum Treated by Mechanical Removal of the Lice and Nits from the Eyelashes and Cutting the Scalp Hair：A Case Report

Purpose：To report a case of phthiriasis palpebrarum in a 5-year-old boy that was treated by mechanical removal of the crab lice and nits from the eyelashes, washing the scalp hair with phenothrin shampoo, and cutting the patient’s long hair.Case：A 5-year-old boy who had erythema and itching in his eyes for several months was presented at Dokkyo Medical University Koshigaya Hospital. The patient had been prescribed 0.1％ fluorometholone and 0.5％ levofloxacin for allergic blepharoconjunctivitis at another pediatric clinic. Slit-lamp examination revealed lice and nits anchored to the eyelashes. Additionally, more than 100 lice and nits were found in the patient’s long scalp hair. The lice and nits were removed from the eyelashes by pulling them with a fine forceps without sedation during three monthly sessions. Furthermore, patient’s parents washed the scalp hair with phenothrin shampoo, and cut it short. The patient completely recovered after 3 months without any further management , and there was no evidence of the lice or nits thereafter.Conclusion：Phthiriasis palpebrarum can be diagnosed by close examination of the eyelashes. Treatment with mechanical removal of the lice and nits from the eyelashes, cutting the long scalp hair, and application of phenothrin shampoo may be effective in treating phthiriasis palpebrarum