Comparison of the copy-neutral loss of heterozygosity identified from whole-exome sequencing data using three different tools

Loss of heterozygosity (LOH) is a genomic aberration. In some cases, LOH can be generated without changing the copy number, which is called copy-neutral LOH (CN-LOH). CN-LOH frequently occurs in various human diseases, including cancer. However, the biological and clinical implications of CN-LOH for human diseases have not been well studied. In this study, we compared the performance of CN-LOH determination using three commonly used tools. For an objective comparison, we analyzed CN-LOH profiles from single-nucleotide polymorphism array data from 10 colon adenocarcinoma patients, which were used as the reference for comparison with the CN-LOHs obtained through whole-exome sequencing (WES) data of the same patients using three different analysis tools (FACETS, Nexus, and Sequenza). The majority of the CN-LOHs identified from the WES data were consistent with the reference data. However, some of the CN-LOHs identified from the WES data were not consistent between the three tools, and the consistency with the reference CN-LOH profile was also different. The Jaccard index of the CN-LOHs using FACETS (0.84 ± 0.29; mean value, 0.73) was significantly higher than that of Nexus (0.55 ± 0.29; mean value, 0.50; p = 0.02) or Sequenza (0 ± 0.41; mean value, 0.34; p = 0.04). FACETS showed the highest area under the curve value. Taken together, of the three CN-LOH analysis tools, FACETS showed the best performance in identifying CN-LOHs from The Cancer Genome Atlas colon adenocarcinoma WES data. Our results will be helpful in exploring the biological or clinical implications of CN-LOH for human diseases.

Two Cases of Tacrolimus-related Transplant-associated Thrombotic Microangiopathy Retinopathy after Allogenic Peripheral Blood Stem Cell Transplantation

Purpose@#We report two cases of tacrolimus-related transplant-associated thrombotic microangiopathy (TA-TMA) retinopathy in leukemia patients who had undergone allogenic peripheral blood stem cell transplantation (PBSCT).Case summary: (Case 1) A 58-year-old woman with a history of PBSCT due to acute myelocytic leukemia and taking tacrolimus was referred to the ophthalmology clinic with visual disturbance. Her visual acuity (VA) was 0.4 in the right eye and 0.5 in the left eye. Multiple cotton wool spots and retinal hemorrhages were found in both eyes on fundus examination. Multiple capillary non-perfusions were seen on fluorescein angiography (FA). Tacrolimus-related TA-TMA retinopathy was suspected. Tacrolimus was discontinued and plasmapheresis was performed. After 3 months, neovascular glaucoma developed and her VA became “counting fingers” at 20 cm in both eyes. (Case 2) A 20-year-old man with a history of PBSCT due to acute lymphocytic leukemia and taking tacrolimus was referred to our clinic because of decreased VA in both eyes. His VA was 0.05 in the right eye and 0.025 in the left eye. Fundus and FA findings were the same as in Case 1, and the patient was suspected to have tacrolimus-related TA-TMA retinopathy. Tacrolimus was discontinued and plasmapheresis was performed. His VA was 0.2 in the right eye and 0.4 in the left eye at 1 month after treatment. @*Conclusions@#It is necessary to consider TA-TMA retinopathy in leukemia patients taking calcineurin inhibitors, such as tacrolimus, who have decreased VA. Early diagnosis and treatment are important.

Changes in Iridocorneal Angle Configuration and Intraocular Pressure during Smartphone Use under Room Light

Purpose@#To investigate changes in intraocular pressure (IOP) and iridocorneal angle (ICA) configuration during smartphone use under room light. @*Methods@#We included healthy adults aged 19-35 years with no ophthalmological abnormalities. All read text on a smartphone for 6 minutes under room light. IOP was measured via rebound tonometry at baseline and at 2, 4, and 6 minutes. ICA images were obtained via anterior segment optical coherence tomography after each IOP measurement. After 6 minutes, participants stopped reading text and rested for 2 minutes. IOP was then measured again. @*Results@#The IOP significantly increased at 2, 4, and 6 minutes of reading compared to baseline (p < 0.001) but recovered to baseline after 2 minutes of rest (p = 1.000). The anterior chamber depth decreased significantly, and the anterior chamber angle width increased after 6 minutes of smartphone reading (both p < 0.05). @*Conclusions@#IOP increased when reading smartphone text under room light but the ICA did not change. Prolonged smartphone reading is inappropriate for a patient at risk of glaucoma or glaucoma progression. Such patients should be cautioned.

Changes in Iridocorneal Angle Configuration and Intraocular Pressure during Smartphone Use under Room Light

Purpose@#To investigate changes in intraocular pressure (IOP) and iridocorneal angle (ICA) configuration during smartphone use under room light. @*Methods@#We included healthy adults aged 19-35 years with no ophthalmological abnormalities. All read text on a smartphone for 6 minutes under room light. IOP was measured via rebound tonometry at baseline and at 2, 4, and 6 minutes. ICA images were obtained via anterior segment optical coherence tomography after each IOP measurement. After 6 minutes, participants stopped reading text and rested for 2 minutes. IOP was then measured again. @*Results@#The IOP significantly increased at 2, 4, and 6 minutes of reading compared to baseline (p < 0.001) but recovered to baseline after 2 minutes of rest (p = 1.000). The anterior chamber depth decreased significantly, and the anterior chamber angle width increased after 6 minutes of smartphone reading (both p < 0.05). @*Conclusions@#IOP increased when reading smartphone text under room light but the ICA did not change. Prolonged smartphone reading is inappropriate for a patient at risk of glaucoma or glaucoma progression. Such patients should be cautioned.

Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells

Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium (MPP+) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

Prediction of Perineural Invasion and Its Prognostic Value in Patients with Prostate Cancer

PURPOSE: The prognostic significance of perineural invasion by prostate cancer is debated. We investigated the association between perineural invasion and clinicopathological factors and the effect of perineural invasion on survival in patients with prostate cancer. MATERIALS AND METHODS: A total of 361 patients with prostate cancer without any neoadjuvant therapies prior to surgery from 1999 to 2010 were analyzed retrospectively. Whole-mount sections of surgical specimens from all patients who underwent radical prostatectomy were evaluated. Positive perineural invasion was defined as infiltration of cancer cells in the perineurium or neural fascicles. The relationship of perineural invasion with clinicopathological features and prognosis of prostate cancer was studied. We also researched preoperative factors that were associated with perineural invasion. RESULTS: Perineural invasion in a prostatectomy specimen (PNIp) was positive in 188 of 361 patients (52.1%). In the multivariate analysis of the preoperative variables, PNIp was related to the primary Gleason grade (p=0.020), the number of positive cores (p=0.008), and the percentage of tumor cells in positive cores (p=0.021), but not to perineural invasion of a prostate biopsy. In the evaluation between PNIp and pathologic findings of the prostatectomy specimen, PNIp was related to the Gleason score (p=0.010), T-stage (p=0.015), and lymphovascular invasion (p=0.019). However, by multivariate analysis, the PNIp was not an independent prognostic factor of biochemical serum recurrence (p=0.364) or cancer-specific survival (p=0.726). CONCLUSIONS: PNIp was significantly related to biologically aggressive tumor patterns but was not a prognostic factor for biochemical serum PSA recurrence or cancer-specific survival in patients with prostate cancer.

Laparoscopic Removal of a Broken Sewing Needle in a Patient with Irritative Bladder Symptoms / 대한배뇨장애요실금학회지

A foreign body near the bladder is rare. Although foreign bodies in the bladder can be easily found and removed by endoscopic transurethral removal, extravesical foreign bodies may require the use of an open or laparoscopic procedure. Here, we report a case of a patient complaining of frequency and urgency in whom an extravesical sewing needle was successfully removed by a laparoscopic approach. A 4.5 cm rusty sewing needle was found between the bladder and the left external iliac vessels and was removed through a 5 mm trocar port by use of endo forceps with no complications.

Quality of Life Impact and Treatment Need According to Frequency of Urinary Stress Incontinence / 대한비뇨기과학회지

PURPOSE: The goal of this study was to investigate the impact on quality of life of urinary incontinence and to examine its relationship with treatment need in community women according to the frequency of stress urinary incontinence(SUI) and SEAPI score. MATERIALS AND METHODS: In 554 of total 811 women, a questionnaire survey was conducted in a typical farming village of a southern region of Korea. The frequencies of SUI were divided into 5 groups(A, less than 12 times/year; B, less than 4 times/month; C, 1 time/week; D, more than 2 times/week; and E, more than 1 time/day) and the SEAPI score into 3 groups according to the sum of all categories(a, 0-5; b, 6-10; and c, 11-15). Each objective criterion was compared with the responders' quality of life indices, cognition indices about symptom and acception indices of treatment. RESULTS: Of the 554 participants, 274(49.5%) had experienced SUI at least once in the last year. In the study of influences on quality of life according to the frequency of SUI and SEAPI score, statistically significant correlations were noted from groups C and b about daily life and social life categories(p<0.05), but not in the sexual life category. Groups E and b had statistically significant correlation in the influences on cognition of symptom(p<0.05). Groups C and b had statistically significant correlation in the influences on the acceptance of treatment (p<0.05). CONCLUSIONS: In spite of its great effect on quality of life, SUI has hardly induced community women to accept the need for its treatment. These findings suggest that more medical education and information about SUI should be offered. These preliminary results may be used as quality of life indices, cognition indices about symptoms and acception indices in future SUI surveys.

A Case of Leiomyosarcoma of the Penis / 대한남성과학회지

Leiomyosarcoma of the penis is an extremely rare disease. We experienced a patient with a leiomyosarcoma on the ventral preputial skin of penis in a 45-year old man. The patient was treated with local wide excision with chemotherapy. Herein, we report this case with the review of literature.

The Study of the Changes of Bladder Permeability by the Method using Transmembrane Resistance in Albumin Sensitized Rat / 대한비뇨기과학회지

No abstract available.

Symptomatic Muscular Ring of the Esophagus / 대한소화관운동학회지

Symptomatic muscular rings are extremely rare, and some authors have even disputed their existence. The lower esophageal muscular ring, or A ring, located about 2cm proximal to the squamocolumnar junction and are covered by squamous epithelium. These rings consist of an annular narrowing of hypertrophic muscular tissue in the esophageal body. Recently, we experienced 2 cases of symptomatic muscular ring of the esophagus and the findings. Case 1) A 52 year-old male with dysphagia, chest pain and regurgitation for several years, had esophagogram, endoscopy, esophageal motility studies and chest CT. Under the diagnosis of esophageal muscular ring, the patient had pneumatic baUoon dilatation (3.0 cm in diameter, Rigiflex), under which the patient experienced perforation of the lower esophagus and required surgery. We confirmed muscular ring of the esophagus as shown by a thickened muscularis propria layer, without other pathologic findings. Case 2) A 60 year-old male complaining of intermittent dysphagia, had esophagogram, endoscopy, esophageal motility studies and EUS. Under the diagnosis of esophageal muscular ring, he is now being treated with calcium channel blocker and nitrate, and has experienced minimal symptom improvement. We report 2 cases of symptomatic muscular ring of low esophagus with review of literature.

A Case of Gas-Bolat Syndrome / 대한소화관운동학회지

Gas-bloat syndrome is a characteristic disease that developed in patients who had symptoms severe enough to warrant surgery for refractory refiux esophagitis. During the first few months, most of patients have significant symptoms and gradually have been improved except some cases. Although the underlying pathophysiology is uncatain, too tense fundoplication could result in an one-way valve peventing most patients from belching or vomiting. This syndrome has been reported in western country for many years but not yet in Korea. We report a case of gas-bloat syndrome after fundoplication for sevete reflux esophagitis and hiatal hemia.

Immunoreactivity of androgen receptor protein in sexually dimorphic spinal motonucleus in neonatal male rats

The spinal motonucleus of the genitofemoral nerve regulating scrotal temperature can also be related to prenatal and neonatal testicular descent by gubernacular change in rats, and a sexually dimorphic-like bulbocavernosus/dorsolateral motonucleus. There is a hypothesis that neonatal androgen affects these motonuclei, and induces development of sexual organs through neural stimulation. Until now, the accumulation of isotope-labelled androgen and the immuno-reactivity of androgen receptor protein in each sexually-dimorphic spinal motonucleus have been revealed in adult rats but they have not been established in rats during neonatal periods. To investigate the presence of the androgen receptor in spinal sexually-dimorphic motonuclei in the neonatal period, we evaluated the androgen receptor immunoreactivity of these motonuclei. In Sprague-Dawley male rats, the lumbar spinal cords were resected at postnatal days 3, 10 and 30, and stained immunohistochemically using polyclonal antibody of androgen receptor protein. The immunoreactivity of androgen receptor protein was observed in the cells of the genitofemoral motonucleus from the 13th thoracic to the 2nd lumbar spinal cord and the bulbocavernosus/dorsolateral motonucleus was observed from the 4th to 5th lumbar spinal cord in all age groups. The proportional areas of both motonuclei at days 3 and 10 on cross-section were larger than at day 30. The motonuclei at days 3 and 10 were similar in all age groups. With the above results, the presence of androgen receptor protein was confirmed in the genitofemoral and bulbocavernosus/dorsolateral motonucleus from neonate to day 30. The larger proportional area of these motonuclei in neonates may indicate an active role for these motonuclei during the neonatal period. Although the immunoreactivity does not directly imply the presence of a functional receptor, neonatal androgen could be responsible for the development of sexual organs through the spinal motonucleus.

10-year Experience with Artificial Urethral Sphincter / 대한비뇨기과학회지

Urinary incontinence is a relatively common and potentially disabling disease affecting the life quality of a patient. Many successful series in the treatment of incontinence by medical or surgical therapy using autologous materials have been reported. However, those who have structural abnormalities, injury around the urethra, and derangements in the nervous system could not be benefited by such treatments. In other countries, the artificial urethral sphincter, introduced in 1972, have achieved satisfactory results and then increased in use; but in Korea, it was not widely used because of many limitations and obstacles. Based on our ten-year experience with 10 cases of implantation of artificial urethral sphincter from 1987 to 1996, we tried to elucidate the present status, problems, and the possible ways of improvements of its use within this country. A total of ten male patients underwent implantations of the AMS Model 800 artificial urethral sphincter. Mean age was 34.5 (17-43) years. Mean follow-up was 4.2 (0.5-10) years. Two patients were spinal cord injury patients, 2 meningomyeloceles, and 6 posterior urethral injuries. Two patients had the prosthesis removed due to infection and cuff erosion. In the other 8 patients, 6 were dry (75.0 %) and 1 was improved (12.5 %) and 1 was wet (12.5 %). The revision rate was 20% (2/10) and overall improvement of incontinence was observed in 7 (87%) patients. The reasons for the low incidence of the implantation of artificial urinary sphincter in this country are as follows. According to the other reports, the most common application of artificial urinary sphincter in the west is in the post-prostatectomy incontinence accounting for about 60% of artificial urinary sphincter implantation whereas in this country, the majority of cases are patients who had trauma. Since radical prostatectomy has not been established well in the country (in the recent 4 years, totally only 53 cases were performed) and also the excellent performance of the transurethral surgery making the incidence of incontinence low, could be one of the reasons. In addition, the high price of the prosthesis over 4 million won and operation fee of 3 to 6 million won is a formidable burden to most patients. In the view of mechanical problem, the cuff size of the urethra in the oriental people is observed smaller than the western, and we must let the company prepare the cuff set of smaller size. In conclusion, if we solve those problems in our country, the artificial urethral sphincter is an effective device for treatment of urinary incontinence in patients who have failed more conservative modes of therapy.

A Case of Lymphatic Metastasis to Ampulla of Vater from Gastric Adenocarcinoma / 대한내과학회지

Cancer of the stomach is responsible for approximately 650,000 deaths globally each year and is probably second only to lung cancer worldwide as an overall cause of cancer-related mortality. Similar to the situation with most adenocarcinomas of the gastointestinal tract, carcinomas of the stomach can spread by local extension to adjacent normal structures and can develop lymphatic, peritoneal, and distant metastases. The tumor cells, can also permeate diffusely into the lymphatic plexus of the bowel, more often at the level of the upper duodenum hut sometimes down into the distal ileum and the large bowel. We report a case of lymphatic metastasis of gastric adenocarcinoma to the ampulla of Vater with review of the literature.

Immunoreactivity of Androgen Receptor Protein in Sexually Dimorphic Spinal Motonucleus in Neonatal Male Rats / 대한비뇨기과학회지

The spinal motonucleus of genitofemoral nerve regulating scrotal temperature also can be related to prenatal and neonatal testicular descent by gubernacular change in rats, and sexually dimorphic like bulbocavernosus/dorsolateral motonucleus. There is a hypothesis that neonatal androgen affects these motonuclei, and induce development of sexual organ through neural stimulation. Until now, the accumulation of isotope labeled androgen and immunoreactivity of androgen receptor protein in each sexually dimorphic spinal motonucleus have been revealed in adult rats but not been established in rats of neonatal periods. To investigate the presence of the androgen receptor in spinal sexually dimorphic motonuclei in neonatal period, we evaluated the androgen receptor immunoreactivity of these motonuclei. In Sprague-Dawley male rats, the lumbar spinal cords were resected according to cord level by laminectomy under dissecting microscope after perform aldehyde perfusion fixation at postnatal day3 (n=6), 10 (n=7) and 30 (n =6). The resected spinal cords were serially sectioned 50 um thick by vibratome, and stained immunohistochemically using polyclonal antibody of androgen receptor protein. The immunoreactivity of androgen receptor protein was observed in the cells of genitofemoral motonucleus from the thirteenth thoracic to the second lumbar spinal cord and bulbocavernosus/ dorsolateral motonucleus was observed from the 4th to 5th lumbar spinal cord at all age groups. The proportional areas of both motonuclei of day 3 and 10 on cross section were larger than that of day 30. The motonuclei of day 3 and 10 were more laterally located, compared to that of day 30. The immunostaining densities were similar in all age groups. With the above results, the presence of androgen receptor protein was confirmed in the genitofemoral and bulbocavernosus/ dorsolateral motonucleus from neonate to day 30. The larger proportional area of these motonuclei in neonates may indicate active role of these motonuclei during neonatal period. Although the immunoreactivity does not directly imply the presence of functional receptor, neonatal androgen could be responsible for the development of sexual organ through the spinal motonucleus.

Effects of Neurotrophic Factor on Fetal Mesencephalic Grafts in Parkinsonian Rat Models

We investigated the usage of basic fibroblast growth factor administration to promote the survival of the dopaminergic neurons and behavioral efficacy of fetal mesencephalic grafts in rat parkinsonian models induced by 6-hydroxydopamine. The authors made partial lesioned rat parkinsonian models in which there was destruction of the dopaminergic nigrostriatal pathway & sparing of the mesolimbic pathway. A basic firoblastic growth factor was given continuously by using osmotic minipump into the lateral ventricle of the rat parkinsonian model for 2 weeks. Twelve weeks after grafts, all of the fetal mesencephalic grafts with basic fibroblast growth factor showed enhancement of the survival of dopaminergic neurons as well as activity of tyrosine hydroxylase in the caudate-putamen. Also, they accelerated the recovery in the grafted animals in test of apomorphine-induced rotational behavior when compare with that of the fetal mesencephalic grafts alone. The levels of tyrosine hydroxylase activity in the caudate-putamen were significantly enhanced in the fetal mesencephalic grafts with basic fibroblast growth factor and basic fibroblast growth factor alone compared with the control group. Those rats with fetal mesencephalic grafts with/without basic fibroblast growth factor or basic fibroblast growth factor alone showed the recovery in tests of apomorphine-induced rotational behaviors. Our study suggests that the basic fibroblast growth factor may be a neurotrophic factor for dopaminergic neurons, or may act indirectly by inducing the release of a dopaminergic trophic factor from other sources.

Double Pylorus: A Case report / 대한소화기내시경학회지

A Case of double pylorus, in 56 year old man, was diagnosed by fiberoptic gastroscopy and upper gastrointestinal series. Two ovoid large openings of pyloric canal divided by smooth thickened septum were observed endoscopically And the relevant literatures on tihe subject were reviewed.

Two cases of primary urethral end to end anastomosis for posterior urethral rupture / 대한비뇨기과학회지

There were two cases of posterior urethral ruptured patient combined with severe pelvic bone disruption. They were treated with primary urethral end to end anastomosis and the results were good. We recommend the primary end to end anastomosis of posterior urethral rupture in some instances those who are ready for good exposure of posterior urethra because of wide pelvic bone disruption favorable patient`s condition and excellent skill of surgeon.

Standards for Korean adult facial relationships by various roentgeno-cephalometric analysis / 대한치과교정학회지

A study was made of a method of rational assessment on the roentgeno-cephalogram in orthodontic practice. Fifty eight measurements were analyzed on the roentgeno-cephalograms of 50 male and 50 female Korean adults with the acceptable profile and the normal occlusion. The means and standard deviations of measurements were studied in male and female groups by various analytic methods, and the sex difference was examined statistically. The obtained data were compared with those of the Japanese and American standards by using a Japanese adults standard polygon chart reported by lizuka and Ishikawa. Amongs of 58 measurements, 14 have been selected as statistically significant and clinically useful, and used to make a Korean adult standard polygon chart. The results obtained were as follows: 1. Standards for cephalometric analysis in Korean adults were obtained, and the polygon chart and cephalometric profilogram were also made by using the standards in order to apply to a clinical diagnosis. 2. The sex difference was recognized in linear measurements, but not in angular measurements. 3. In comparison with the American standards from Downs and Graber, the Korean showed significant differences in angle of convexity, mandibular plane angle, Y-axis angle, interincisal angle and lower incisor to mandibular plane angle. Thus, the Korean showed a more retruded chin position, convex facial type, than white people. 4. In comparison with the Japanese standards from Iizuka and Ishikawa, the Korean showed a significant similarity with the Japanese, especially in females. 5. Upper incisor to Huxely line angle, established as a new measurement, proved to be paralell to X-Y axis angle.