• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1589-1595
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• 2014

Objective: Forkhead box C2 (FOXC2) is a member of the winged helix/forkhead box (Fox) family of transcription factors. It has been suggested to regulate tumor vasculature, growth, invasion and metastasis, although it has not been studied in cervical cancer. Here, we analyzed FOXC2 expression in cervical tissues corresponding to different stages of cervical cancer development and examined its correlation with clinicopathological characteristics. In addition, we examined the effects of targeting FOXC2 on the biological behavior of human cervical cancer cells. Methods: The expression of FOXC2 in normal human cervix, CIN I-III and cervical cancer was examined by immunohistochemistry and compared among the three groups and between cervical cancers with different pathological subtypes. Endogenous expression of FOXC2 was transiently knocked down in human Hela and SiHa cervical cells by siRNA, and cell viability and migration were examined by scratch and CCK8 assays, respectively. Results: In normal cervical tissue the frequency of positive staining was 25% (10/40 cases), with a staining intensity (PI) of $0.297{\pm}0.520$, in CIN was 65% (26/40cases), with a PI of $3.00{\pm}3.29$, and in cancer was 91.8% (68/74 cases), with a PI of $5.568 {\pm}3.449$. The frequency was 100% in adenocarcinoma (5/5 cases) and 91.3% in SCCs (63/69 cases). The FOXC2 positive expression rate was 88.5% in patients with cervical SCC stage I and 100% in stage II, showing significant differences compared with normal cervix and CIN. With age, pathologic differentiation degree and tumor size, FOXC2 expression showed no significant variation. On transient transfection of Hela and SiHa cells, FOXC2-siRNA inhibition rates were 76.2% and 75.7%; CCK8 results showed reduced proliferation and relative migration (in Hela cells from $64.5{\pm}3.16$ to $49.5{\pm}9.24$ and in SiHa cells from $60.1{\pm}3.05$ to $44.3{\pm}3.98$) (P < 0.05). Conclusion: FOXC2 gene expression increases with malignancy, especially with blood vessel hyperplasia and invasion degree. Targeted silencing was associated with reduced cell proliferation as well as invasion potential.

• The Korean Journal of Nuclear Medicine
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• v.14 no.1
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• pp.1-8
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• 1980

Serum TSH levels were measured by radioimmunoassay before and after intravenous administration of synthetic thyrotropin-releasing hormone (TRH) to 15 normal subjects and 55 patients with primary thyroid disease (14 patients with euthyroidism, 24 patients with thyrotoxicosis and 17 patients with hypothyroidism) to evaluate pituitary TSH reserve and its diagnostic availability. The observed results were as follows. 1. In normal subjects, serum TSH responses to synthetic TRH were $3.2{\pm}1.0$ at 0min (baseline TSH level), $8.0{\pm}4.0$ at 10min, $11.7{\pm}5.0$ at 20min, $13.7{\pm}7.1$ at 30min, $9.7{\pm}5.0$ at 60min., $5.2{\pm}2.0$ at 120min. and $3.6{\pm}0.4{\mu}U/ml$ at 180 min. Serum TSH peaked at $20{\sim}30$ minutes and returned nearly to baseline at 180minutes. 2. In euthyroid group, serum TSH responses to synthetic TRH were $3.3{\pm}1.6$ at 0min, $8.6{\pm}8.0$ at 10min, $10.9{\pm}8.5$ at 20min, $12.5{\pm}8.4$ at 30min, $9.0{\pm}5.9$ at 60min, $5.6{\pm}2.6$ at 120min and $3.5{\pm}1.3{\mu}U/ml$ at 180min. No significant difference revealed between euthyroid group and normal subjects (p>0.05). 3. In hyperthyroid group, serum TSH responses to synthetic TRH were $1.5{\pm}0.6$ at 0min, $2.2{\pm}0.8$ at 10min., $2.3{\pm}1.0$ at 20min., $2.4{\pm}1.5$ at 30min., $2.1{\pm}1.1$ at 60min., $1.9{\pm}0.2$ at 120min. and $1.5{\pm}0.8{\mu}U/ml$ at 180min., No response to TRH showed. 4. In hypothyroid group, mean values of serum TSH response to synthetic TRH were 42.0 at 0min., 60.6 at 10min., 124.8 at 20min., 123.0 at 30min., 101.6 at 60min., 64.3 at 120min. and $15.5{\mu}U/ml$ at 180 min., Patients with primary hypothyroidism showed an exaggerated TSH response to synthetic TRH despite their high basal TSH. 5. Side effects attending synthetic TRH administration were transient nausea (59.0%), desire to micturate (59.0%), feeling of flushing(19.7%), dizziness (45.9%), metallic taste (9.8%) and headache (19.7%). Any side effect didn't show in 16.4%. These symptoms began almost immediately after TRH intravenous injection and lasted several minutes, and not related to dose or response in the person experiencing it.

• Clinical and Experimental Pediatrics
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• v.50 no.2
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• pp.209-212
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• 2007

Acrodermatitis enteropathica (AE) is a rare autosomal recessive disorder of early infancy, and is characterized by periorificial dermatitis, alopecia, and intractable diarrhea. Serum zinc levels are usually low in untreated patients and the oral administration of zinc sulfate can clear skin lesions and other symptoms. Although premature and cow's milk-fed infants are at particular risk of developing AE, there have been a few reports about AE in term and breast-fed infants. We report a case of transient AE in a 4-month-old breast-fed infant. This patient suffered from diarrhea and dermatitis for more than a month. Her skin lesions were erythematous, scaly, crusted, psoriasiform, eczematous, with an eruption at the chin, and a periorificial disposition with involvement of the flexural areas of lower extremities. Her serum zinc level was almost normal at $129{\mu}g/dL$ (reference range: $60-121{\mu}g/dL$), but the zinc level in her hair was low: 8 mg percent (reference range: 10-21 mg percent). Skin biopsy findings were consistent with AE. Seven days after zinc supplementation, the skin lesions and diarrhea improved. The authors recommend that a clinical trial of zinc supplementation be considered in cases where there are suspicious of AE, even when the serum zinc level is normal.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1611-1618
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• 2007

In this study we investigated the effect of medical history on the incidence of stroke in Korean population. 217 stroke patients were enrolled as a case group. 160 non-stroke patients and 146 normal and non-stroke patients were enrolled as a control and a normal group, respectively, from Jul. 2005 to Mar. 2007. Stroke patients were hospitalized within 2 weeks after the onset of stroke. Medical history was gathered by interviewing each patient. Clinical data were analyzed using SAS software (ver 9.1). Hypertension and diabetes mellitus (DM) were statistically significant in a case group when compared with control and normal groups. Other parameters, such as transient ischemic attack, hyperlipidemia, ischemic heart disease, facial palsy, migraine, and hypochondria, did not show any statistical significance. The same association pattern was observed in the ischemic stroke patients of case group. On the other hand, hemorrhagic stroke patients of case group showed a significant difference in DM when compared with other subject groups. More efficient therapeutic strategy should be considered for patients with medical history, especially hypertensin and DM, to reduce the stroke incidence in Korean population.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.753-759
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• 2005

Purpose : This study was performed to characterize clinical features of benign convulsions with gastroenteritis(CwG) in infants. Methods : We reviewed clinical features of 67 episodes in 64 patients with afebrile seizure accompanied gastroenteritis admitted to Dept. of Pediatrics Bundang CHA hospital from January 2001 to June 2004. Patients with meningitis, encephalitis/encephalopathy or apparent history of epilepsy were excluded. Results : There were 32 boys and 35 girls. The age of onset ranged from 1 to 42 months($18.5{\pm}6.1$ months). The number of children admitted to the hospital with acute gastroenteritis was 2,887 in the same period. The percentage of patients with CwG was 2.3. Seizure type was exclusively generalized tonic or tonic-clonic seizure. The average number of seizures during a single episode was 3.1 (range, 1-13). Two or more seizures occurred in 53(79.1%) of the 67 episodes. Antiepileptic drugs were administered for 42 episodes. Seizure did not cease after the administration of one kind of antiepileptic drug in 23 episodes(54.7%). The seizures were rather refractory to initial antiepileptic treatment. There were no abnormalities in serum biochemistry test including glucose and electrolytes. Cerebrospinal fluid was normal in all 54 episodes. Stool cultures were negative in 49 episodes. Rotavirus was positive in stools in 51(82.3%) of 62 episodes. Norovirus was positive in stools in 2 episodes and astrovirus in 1 of 18 episodes. CT and/or MRI were performed in 15 cases and demonstrated no neuroradiologic abnormalities. Of 73 Interictal EEG, initial 24 cases showed occasional spike or sharp wave discharges from the mid-line area during stage I-II sleep, which were apparently differentiated from vertex sharp transient or K-complexes. The mean follow-up period was 5.7 months(1-36 months). Three patients experienced a recurrence of CwG, but all patients exhibited normal psychomotor development at the last follow-up. Conclusion : Afebrile infantile convulsions with gastroenteritis are brief generalized seizure in cluster with normal laboratory findings and good prognosis. Therefore CwG is likely to be categorized as situation-related seizure of special syndrome. Recognition of this entity should lead to assurance of the parents and long-term anticonvulsant therapy is not usually warranted.

• Journal of Korean Neurosurgical Society
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• v.29 no.2
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• pp.222-230
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• 2000

Purpose : Resection of the epileptogenic zone in the parietal and occipital lobes may be relevant although only few studies have been reported. Methods : Eight patients with parietal epilepsy and nine patients with occipital epilepsy were included for this study. Preoperatively, all had video-EEG monitoring with extracranial electrodes, MRI, 3D-surface rendering of MRI using Allegro(ISG Technologies Inc., Toronto, Canada), and PET scans. Sixteen patients underwent invasive recording with subdural grid. Eight had parietal resection including the sensory cortex in two. Seven had partial occipital resection. Two underwent total unilateral occipital lobectomy. The extent of the resection was made based mainly on the data of invasive EEG recordings, MRI, and 3D-surface rendering of MRI, not on the intraoperative electrocorticographic findings as usually done. During resection, electrocortical stimulation was performed on the motor cortex and speech area. Results : Out of eight patients with parietal epilepsy, three had sensory aura, two had gustatory aura, and two had visual aura. Six of nine patients with occipital epilepsy had visual auras. All had complex partial seizures with lateralizing signs in 15 patients. Four had quadrantopsia. One had mild right hemiparesis. Abnormality in MRI was noticed in six out of eight parietal epilepsy and in eight out of nine occipital epilepsy. 3D-surface rendering of MRI visualized volumetric abnormality with geometric spatial relationships adjacent to the normal brain, in all of parietal and occipital epilepsy. Surface EEG recording was not reliable in localizing the epileptogenic zone in any patient. The subdural grid electrodes can be implanted on the core of the structural abnormality in 3D-reconstructed brain. Ictal onset zone was localized accurately by subdural grid EEGs in 16 patients. Motor cortex in nine and sensory speech area in two were identified by electrocortical stimulation. Histopathologic findings revealed cortical dysplasia in 10 patients ; tuberous sclerosis was combined in two, hamartoma and ganglioglioma in one each, and subpial gliosis in six. Eleven patients were seizure free at follow-up of 6 months to 37 months(mean 19.7 months) after surgery. Seizures recurred in two and were unchanged in one. Six produced transient sensory loss and one developed hemiparesis and tactile agnosia. One revealed transient apraxia. Two patients with preoperative quadrantopsia developed homonymous hemianopsia. Conclusion : This study suggests that surgical treatment was relevant in parietal and occipital epilepsies with good surgical outcome, without significant neurologic sequelae. Neuroimaging studies including conventional MRI, 3Dsurface rendering of MRI were necessary in identifying the epileptogenic zone. In particular, 3D-surface rendering of MRI was very helpful in presuming the epileptogenic zone in patients with unidentifiable lesion in the conventional MRI, in planning surgical approach to lesions, and also in making a decision of the extent of the epileptogenic zone in patients with identifiable lesion in conventional MRI. Invasive EEG recording with the subdural grid electrodes helped to confirm a core of the epileptogenic zone which was revealed in 3D-surface rendered brain.

• Journal of Korean Neurosurgical Society
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• v.58 no.3
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• pp.167-174
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• 2015

Objective : This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). Methods : Twenty Sprague-Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. Results : In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. Conclusion : Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD.

• The Plant Pathology Journal
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• v.24 no.3
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• pp.296-304
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• 2008

The transient and rapid expression system of a foreign protein in planta is a very useful technique in biotechnology application. We have investigated optimum condition of Agrobacterium-infiltration technique in which expression level of foreign proteins were maximized without detrimental effects on plants using GFP and Cucumber mosaic virus 2b protein, which is known as an enhancer of gene expression and a suppressor of post-transcriptional gene silencing(PTGS). The optimum expression level of both RNA and protein of GFP with minimum leaf impairment was obtained at $OD_{600}$=0.2 of Agrobactrium inocula. The steady-state levels of GFP RNA and protein generally peaked at 3 and 7 days post-infiltration(dpi), respectively. In the presence of 2b, both the magnitude and duration of GFP expression was highly increased and we could detect GFP level until 17 dpi. On the other hands, the 2b-mediated higher accumulation of foreign proteins resulted in the repression of normal leaf growth, possibly due to the limitation of supply of energy or materials required for growth maintenance. Using this Agrobacterium-infiltration system with 2b and GFP, we tested a hypothesis for the threshold model of PTGS initiation. Four GFP transgenic lines of N. benthamiana, which shows different expression level of GFP were tested to determine the threshold level for PTGS initiation. Agrobacterium-infiltration of GFP into those GFP-transgenic plants resulted in the co-silencing of the transgenic GFP. It was found that very low concentration of Agrobacterium with GFP and GFP+2b($OD_{600}$=0.002-0.02) which could not phenotypically induce an additive GFP expression, was enough to trigger PTGS pathway in all GFP transgenic plants. This strongly indicates that each GFP-transgenic plant should be expressing the transgenic GFP at its own pre-determined level and there was no buffer zone of additive GFP-expression to the threshold. In other words, the PTGS seems to be immediately activated as a self-defensive mechanism if an internal balance of gene expression is broken.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3437-3445
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• 2016

Background: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be down-regulated in clinical samples, most likely due to the post-transcriptional modification by microRNAs. Targeted genes would be up-regulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. Materials and Methods: MicroRNA software predicted that miR-21 targets VCL while miR-29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalin-fixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE-1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. Results: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down-regulated while CX3CL1 was up-regulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly upregulated while CX3CL1 mRNA was significantly down-regulated compared to the RWPE-1 case. Conclusions: The down-regulation of VCL in FFPE specimens is most likely regulated by miR-21 based on the in vitro evidence but the exact mechanism of how miR-21 can regulate VCL is unclear. Up-regulated in CaP, CX3CL1 was found not regulated by miR-29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNA-mRNA interactions may provide additional knowledge for individualized study of cancers.

• Clinics in Shoulder and Elbow
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• v.16 no.2
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• pp.107-114
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• 2013

Purpose: This study is designed to evaluate the clinical and radiographical results for the displacement of fracture fragments after interlocking intramedullary nailing in humeral shaft fractures. Materials and Methods: We retrospectively reviewed the results of 8 cases of humeral shaft fractures that have displacements of over 10 mm and under 20 mm after interlocking intramedullary nailing between July 2004 and August 2011. The mean age was 54.1 years (range, 43 to 70 years) and there were 3 male and 5 female patients. Radiographically, the time to bony union, change of displacement and angulation of the fracture site, and degree of improvement of these two factors were measured. Clinically, the range of motion of shoulder and elbow joints, postoperative pain and complications were evaluated. Results: All cases showed complete bony union in last follow-up. The mean time to bony union was 16.1 weeks. At the last follow-up, almost all cases had normal range of motion of shoulder and elbow joints. But, one case had stiffness of shoulder joint. Therefore, arthroscopic capsular release and manipulation was performed. One case had transient shoulder pain and the other case had transient elbow pain. In the two cases, pull-out of proximal interlocking screw were noted, but they finally had bony union. Conclusion: Although considerable displacement of fracture fragments after interlocking intramedullary nailing in humeral shaft fractures was present, we had excellent radiographical and clinical outcomes. Therefore, an additional procedure, such as open reduction or another fixation for the fracture site, was not necessary.