Curved-Tip Disposable Injector (OUReP Injector) to Insert Photoelectric Dye-Coupled Polyethylene Film (OUReP) as Retinal Prosthesis into Subretinal Space of Rabbit Eyes

The photoelectric dye-coupled thin polyethylene film functions as a novel type of retinal prosthesis in subretinal space of the eye. We previously reported a novel disposable injector to insert the thin film into subretinal space of the rabbit eye by vitreous surgery. The injection system composed of two separate parts, injector and loader. A circular film in 5 mm to 10 mm diameter was pulled into a transparent tube of the loader with a commercial 25-gauge forceps. The loader tube was joined with a sleeve to tube tip of the injector. The film in the loader was pushed with a plunger for the loader into the injector tube tip. The loader with the sleeve was removed from the injector tip, and the tube tip with the film was filled with solution. This study reported a small-bore curved-tip disposable injector with outer diameter of 1.6 mm. A curved-tip polypropylene tube was formed by the process of heating and cooling of the tube inserted with a curved guide wire. The plunger for the curved-tip tube was made of a polyphenylsulfone tip connected with a press-fitting inner polypropylene tube to a nylon rod. Bleb retinal detachment in 4 surgically aphakic eyes of rabbits were induced by infusing solution into subretinal space with a 38-gauge polyimide tip, and a retinal tear was made at the edge of retinal detachment with 25-gauge diathermy. The injector tip with the rolled film in 6 mm diameter was inserted from 2 mm wide scleral incision into vitreous and then into subretinal space. The rolled films were released into subretinal space with the tip end inserted into the retinal tear, and the released films were confirmed to stay under the retina with no additional aid. Dissection one month after surgeries confirmed successful implantation of 4 films into subretinal space of each rabbit eye. The curved-tip injector could release the rolled film into the subretinal space without additional effort, compared with the straight-tip injector, and would help surgeons implant photoelectric dye-coupled thin film retinal prosthesis easily at vitreous surgery

Three cases of endoscopic treatment for bronchial obstruction using a balloon catheter.

背景．バルーンカテーテルの使用により，容易に摘出ができた気道閉塞の３例を経験したので報告する。症例１．80歳女性。呼吸困難で受診，胸部computed tomography（CT）で左主気管支内の高濃度領域と左無気肺を認めた。気管支鏡検査で左主気管支内に粘液栓を認め，バルーンカテーテルを用いて摘出した。病理所見でアスペルギルス菌糸を認めアレルギー性気管支肺アスペルギルス症と診断した。症例２．89歳女性。食事中の呼吸困難で受診，胸部CT で左主気管支内の異物，左無気肺を認めた。気管支鏡検査で鶏肉の咀嚼物と考えられる異物を認め，バルーンカテーテルを用いて摘出した。症例３．77歳男性。呼吸困難で受診，胸部CT で左主気管支内に異物，左無気肺を認めた。気管支鏡検査でティッシュペーパーと考えられる異物を認め，バルーンカテーテルで摘出した。結論。気管支閉塞物の内視鏡的治療を行う際は，形態や性状に応じて適切なデバイスを選択する必要がある。本３症例の内視鏡治療においては，バルーンカテーテルが特に有用であった。Background. We herein report three cases of bronchial obstruction that was easily removed using a balloon catheter. Case 1. An 80-year-old woman visited the hospital because of dyspnea. Chest computed tomography （CT） showed a high-density area in the left main bronchus and left atelectasis. Bronchoscopy revealed a mucous plug obstructing the left main bronchus and was removed using a balloon catheter. Pathological findings revealed aspergillus hyphae, and the patient was diagnosed with allergic bronchopulmonary aspergillosis. Case 2. An 89-year-old woman visited the hospital because of dyspnea during meals. Chest CT showed a foreign body in the left main bronchus and left atelectasis. Bronchoscopy revealed a foreign body, identified as chicken residue, and was removed using a balloon catheter. Case 3. A 77-year-old man visited the hospital because of dyspnea. Chest CT showed a foreign body in the left main bronchus and left atelectasis. Bronchoscopy revealed a foreign body, identified as tissue paper, and was removed using a balloon catheter. Conclusion. During bronchoscopy, an appropriate device should be selected according to the shape and properties of the bronchial obstruction. Balloon catheters were particularly useful in the bronchial endoscopic treatment of the three above mentioned cases

Minilaparotomy Approach for Giant Mutinous Cystadenoma of the Ovary in Children: Report of Two Cases

Mucinous cystadenomas (MCAs) are rare benign neoplasms in children. To the best of our knowledge, only 22 cases in children have been described. MCAs may reach huge sizes, and thus are not readily amenable to laparoscopic treatment due to the risk of rupture and the limited working space. We report two cases of giant MCA of the ovary treated by minilaparotomy. In case 1, a 12-year-old girl was admitted with abdominal pain and vomiting. Diagnostic imaging showed a large polycystic mass occupying nearly the whole abdominal cavity. With a provisional diagnosis of ovarian cyst, surgery was performed. The cyst was punctured under direct vision though a small subumbilical incision. After aspiration of 2,000ml of mucinous fluid, laparoscopic examination revealed a tumor originating from the left ovary. Left oophorectomy was performed through an 8-cm incision in the left lower abdomen. The histopathological diagnosis was MCA. In case 2, a 15-year-old girl presented with slowly increasing abdominal distension over 5 months. A polycystic mass measuring 36 × 21 × 14cm was evident on imaging. After drainage of 9,500ml of clear mucinous fluid, right oophorectomy was performed through a small (5cm) midline incision. The final pathology revealed a benign MCA. No recurrence has been detected for 2 years postoperatively in case 1 and for 6 years postoperatively in case 2

Geographic variations of wood properties of Larix sibirica naturally grown in Mongolia

Geographic variations in growth, stress-wave velocity of stem, dynamic Youngâs modulus of stems and logs, annual ring width, latewood percentage and basic density were investigated for (Münchh.) Ledeb. naturally grown in Mongolia. A total of 250 trees with 20 to 30 cm in stem diameter at a height of 1.3 m above ground level were selected from each natural stand in five different provenances in Mongolia. In addition, five trees in each stand were cut for measuring dynamic Youngâs modulus of stems and logs, annual ring width, latewood percentage and basic density. Mean values of stress-wave velocity of stems in each stand ranged from 2.92 to 3.41 km s, and the mean value of five stands was 3.23 km s. Mean values of dynamic Youngâs modulus of logs in each stand ranged from 5.17 to 9.72 GPa. A significant correlation (â=â0.798, â<â0.01) was found between stress-wave velocity of stems and dynamic Youngâs modulus of logs. Among the five stands, the highest and the lowest values of average annual ring number were 193 and 44, respectively. Mean values of basic density in five trees within each stand were examined and ranged from 0.52 to 0.56 g cm. Significant differences among five stands were found in tree height, stress-wave velocity of stem, dynamic Youngâs modulus of stems and logs, annual ring width and latewood percentage, suggesting that trees naturally grown in Mongolia have geographic variations in mechanical properties of wood.Larix sibiricaâ1â1rpâ3L. sibiric

Supranormal orientation selectivity of visual neurons in orientation-restricted animals

Altered sensory experience in early life often leads to remarkable adaptations so that humans and animals can make the best use of the available information in a particular environment. By restricting visual input to a limited range of orientations in young animals, this investigation shows that stimulus selectivity, e.g., the sharpness of tuning of single neurons in the primary visual cortex, is modified to match a particular environment. Specifically, neurons tuned to an experienced orientation in orientation-restricted animals show sharper orientation tuning than neurons in normal animals, whereas the opposite was true for neurons tuned to non-experienced orientations. This sharpened tuning appears to be due to elongated receptive fields. Our results demonstrate that restricted sensory experiences can sculpt the supranormal functions of single neurons tailored for a particular environment. The above findings, in addition to the minimal population response to orientations close to the experienced one, agree with the predictions of a sparse coding hypothesis in which information is represented efficiently by a small number of activated neurons. This suggests that early brain areas adopt an efficient strategy for coding information even when animals are raised in a severely limited visual environment where sensory inputs have an unnatural statistical structure

ACTN1 Mutations Cause Congenital Macrothrombocytopenia

Congenital macrothrombocytopenia (CMTP) is a heterogeneous group of rare platelet disorders characterized by a congenital reduction of platelet counts and abnormally large platelets, for which CMTP-causing mutations are only found in approximately half the cases. We herein performed whole-exome sequencing and targeted Sanger sequencing to identify mutations that cause CMTP, in which a dominant mode of transmission had been suspected but for which no known responsible mutations have been documented. In 13 Japanese CMTP-affected pedigrees, we identified six (46%) affected by ACTN1 variants cosegregating with CMTP. In the entire cohort, ACNT1 variants accounted for 5.5% of the dominant forms of CMTP cases and represented the fourth most common cause in Japanese individuals. Individuals with ACTN1 variants presented with moderate macrothrombocytopenia with anisocytosis but were either asymptomatic or had only a modest bleeding tendency. ACTN1 encodes α-actinin-1, a member of the actin-crosslinking protein superfamily that participates in the organization of the cytoskeleton. In vitro transfection experiments in Chinese hamster ovary cells demonstrated that altered α-actinin-1 disrupted the normal actin-based cytoskeletal structure. Moreover, transduction of mouse fetal liver-derived megakaryocytes with disease-associated ACTN1 variants caused a disorganized actin-based cytoskeleton in megakaryocytes, resulting in the production of abnormally large proplatelet tips, which were reduced in number. Our findings provide an insight into the pathogenesis of CMTP

The serum amyloid A3 promoter-driven luciferase reporter mice is a valuable tool to image early renal fibrosis development and shows the therapeutic effect of glucosyl-hesperidin treatment

Tubulointerstitial fibrosis is a progressive process affecting the kidneys, causing renal failure that can be life-threatening. Thus, renal fibrosis has become a serious concern in the ageing population; however, fibrotic development cannot be diagnosed early and assessed noninvasively in both patients and experimental animal models. Here, we found that serum amyloid A3 (Saa3) expression is a potent indicator of early renal fibrosis; we also established in vivo Saa3/C/EBPβ-promoter bioluminescence imaging as a sensitive and specific tool for early detection and visualization of tubulointerstitial fibrosis. Saa3 promoter activity is specifically upregulated in parallel with tumor necrosis factor α (TNF-α) and fibrotic marker collagen I in injured kidneys. C/EBPβ, upregulated in injured kidneys and expressed in tubular epithelial cells, is essential for the increased Saa3 promoter activity in response to TNF-α, suggesting that C/EBPβ plays a crucial role in renal fibrosis development. Our model successfully enabled visualization of the suppressive effects of a citrus flavonoid derivative, glucosyl-hesperidin, on inflammation and fibrosis in kidney disease, indicating that this model could be widely used in exploring therapeutic agents for fibrotic diseases.This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to No. Y)

Frequent loss of HLA alleles associated with copy number-neutral 6pLOH in acquired aplastic anemia

Idiopathic aplastic anemia (AA) is a common cause of acquired BM failure. Although autoimmunity to hematopoietic progenitors is thought to be responsible for its pathogenesis, little is known about the molecular basis of this autoimmunity. Here we show that a substantial proportion of AA patients harbor clonal hematopoiesis characterized by the presence of acquired copy number-neutral loss of heterozygosity (CNN-LOH) of the 6p arms (6pLOH). The 6pLOH commonly involved the HLA locus, leading to loss of one HLA haplotype. Loss of HLA-Aexpression from multiple lineages of leukocytes was confirmed by flow cytometry in all 6pLOH(+) cases. Surprisingly, the missing HLAalleles in 6pLOH(+) clones were conspicuously biased to particular alleles, including HLA-A*02:01, A*02:06, A*31:01, and B*40:02. A large-scale epidemiologic study on the HLA alleles of patients with various hematologic diseases revealed that the 4 HLA alleles were over-represented in the germline of AA patients. These findings indicate that the 6pLOH(+) hematopoiesis found in AA represents "escapes"hematopoiesis from the autoimmunity, which is mediated by cytotoxic T cells that target the relevant autoantigens presented on hematopoietic progenitors through these class I HLAs. Our results provide a novel insight into the genetic basis of the pathogenesis of AA. © 2011 by The American Society of Hematology

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML