Netrin-1 Specifically Enhances Cell Spreading on Fibronectin in Human Glioblastoma Cells

Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against alpha v integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin alpha v beta 3. Since the alpha v subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.

Tyrphostin ErbB2 Inhibitors AG825 and AG879 Have Non-specific Suppressive Effects on gp130/ STAT3 Signaling

Although the interaction between gp130 and the ErbB family has frequently been shown in cancer cells, the mechanism of this interaction remains unclear and controversial. In the present study, we found that specific tyrphostin inhibitors of ErbB2 (AG825 and AG879), but not ErbB1 inhibitor (AG1478), suppressed IL-6-induced tyrosine phosphorylation of STAT3 in schwannoma cells. However, biochemical evidence for transactivation of ErbB2 by IL-6 was not observed. Additionally, the inhibition of ErbB2 expression, with either a specific RNAi or transfection of an ErbB2 mutant lacking the intracellular domain did not inhibit the IL-6-induced tyrosine phosphorylation of STAT3. Thus, it seems that tyrphostins, which are known as specific inhibitors of the ErbB2 kinase, may have non-specific suppressive effects on the IL-6/STAT3 pathway.

RPE Cell Apoptosis by the Combination Treatment of SAHA and Lactacystin

PURPOSE: To establish a new therapeutic strategy for proliferative vitreoretinopathhy (PVR), we examined the effect of combined treatment with HDAC inhibitor SAHA and proteasome inhibitor lactacystin in human retinal pigment epithelial (RPE) cells, ARPE-19. METHODS: Viability was determined by trypan blue exclusion assay. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Proteasome activity was measured by fluorophotometry. The expression and degradation of apoptosis-related proteins were assesssed by Western blotting. Subcellular location of apoptosis-related factors was monitored by confocal miscroscopy. RESULTS: A single treatment with 5 micro M SAHA or 10 micro M lactacystin did not reduce cell viability. However, combination treatment with 5 micro M SAHA and 10 micro M lactacystin substantially reduced the viability, because the mixture induced the reduction of MMP and nuclear condensation or fragmentation. Moreover, the combination treatment triggered the activation of caspase-3 and the production of PARP cleavage products. These data indicate that the combination treatment efficiently induces apoptosis in ARPE-19 cells. However, co-treatment of SAHA did not augment the proteasome inhibitory activity of lactacystin, nor did co-treatment of lactacystin augment acetylation of histones. It is notable that while p53 and CAD were observed in the mitochondria of cells treated with SAHA, they were translocated into the nucleus after the combination treatment. CONCLUSIONS: These results suggest that the combination treatment of SAHA and lactacystin effectively induced apoptosis in ARPE-19 cells. Further work is warranted to develop this combination therapy as a novel therapeutic strategy for PVR.

The Developmental Outcomes of Infantile Spasm / 대한소아신경학회지

PURPOSE:Infantile spasm is the most important epilepsy syndrome that brings catastrophic results in childhood. Persistent spasms and hypsarrhythmia have been known to regress the brain maturation and development. Therefore, it is very important in these patients to find a way to achieve developmental progress as good as possible. The objective of this study was to compare the influence of various etiology on developemental outcome and to determine which therapy has a more favorable development outcome. METHODS:We reviewed 95 children diagnosed as infantile spasm between 1991 and 2005 at College of Medicine of Yonsei University and Sang-gye Paik Hospital. We compared possible factors to predict the developmental outcomes in terms of patient characteristics, etiology, seizure duration and seizure outcomes along with various treatment modalities such as antiepileptic drugs, steroid, ketogenic diet, and surgery. RESULTS:Mental retardation occured in 81(85.3%) of the patients with infantile spasms and 38(40.0%) suffered from propound mental retardation. In predicting the developmental outcomes, the most important factor was found to be the etiology. While only 13(56.5%) patients with cryptogenic infantile spasms had severe to profound mental retardation, 53(73.6%) patients with symptomatic etiologies did. Other factors shown to be associated with a good progress included high developmental scores at the onset, a short duration of spasms, an early effective control of spasms, early consideration of non-pharmacologic treatment such as ketogenic diet and surgery when the seizures filed to respond to antiepileptic drugs. CONCLUSION:This retrospective review suggests that it is possible to improve the developmental outcomes of infantile spasms by making correct etiologic diagnosis and providing early appropriate therapy chosen from variable treatment modalities.

A Case of Congenital Fiber Type Disproportion with Multiple Anomalies / 대한소아신경학회지

Congenital fiber type disproportion (CFTD) is a rare form of congenital myopathy characterized by the smallness and the marked predominance of type 1 fibers, which presents congenital hypotonia, delayed motor milestones, joint contractures, and skeletal deformities. The muscle biopsy reveals the type 1 fibers are more than 12% smaller than the type 2 fibers in size. We describe a 24-month-old boy who presented muscle hypotonia, delayed motor milestones, mental retardation with generalized tonic clonic seizures, and the muscle pathologic findings of CFTD. Additional findings included left cryptorchidism, congenital subluxation of the hip, contractures of ankle joints, diffuse brain atrophy, and optic nerve atrophy. We should consider CFTD as a differential diagnosis of early onset myopathy.

The Effects of Alcohol on Nasal Patency and Mucociliary Clearance

MATERIALS AND METHODS: Fifteen healthy volunteers were studied to evaluate the effects of alcohol ingestion on nasal mucosa over time and changes in mucociliary function after alcohol ingestion. Nasal patency was evaluated with acoustic rhinometry, and mucociliary clearance was measured with a saccharine test. RESULTS: The cross-sectional area of the I-notch and the Cnotch did not change after alcohol ingestion. The cross-sectional area of the posterior part of the nasal cavity (CA 6.4) indicated changes more prominently than that of the anterior part (CA 3.3). A significant reduction in total nasal volume was first noted at 1.5 hours after alcohol ingestion and lasted for 1.5 hours. The saccharine transit time did not change significantly. CONCLUSION: There was no acute impairment of mucociliary function at moderate concentrations of alcohol.

Clinical Characteristics of Angiocentric Immunoproliferative Lesions in Head and Neck / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The histologic features of polymorphic reticulosis are identical to those of sinonasal "angiocentric immunoproliferative lesions" (AILs) which are characterized by angiocentric and angioinvasive lymphoid infiltrates with a wide range of cytologic atypia. 1) This report was conducted to further define the clinicopathological nature of this lesion and evaluate the important prognostic factors and therapeutic strategies. MATERIALS AND METHODS: The clinical features and therapeutic outcomes of 22 patients with AILs were reviewed. Histologic grading was performed by using previously reported criteria (Grade I-III).2) To clarify the cell origin of AIL, immunohistochemical studies were performed in 21 cases. RESULTS: On the slide review, 10 cases were Grade II and 12 cases were grade III which showed characteristic histologic features similar to those of peripheral T-cell lymphoma. On immunohistochemical studies, neoplastic cells of all patients had a T-cell phenotype. The difference in primary treatment results according to the histologic grade, clinical staging and therapeutic modalities was not significant statistically. The overall 5 year survival rates were 58%. CONCLUSION: Our results suggest strongly that quite a significant portion of AIL may be in fact T-cell lymphoma. The only significant prognostic factor that predicts better survival is the achievement of initial complete response.

A Case of Ethmoid Mucocele with Superimposed Fungal Infection / 대한이비인후과학회지

Mucocele is a benign, chronic, expansive and cyst-like lesion of the paranasal sinuses and contains mucoid secretions. The secretion is usually sterile, however, secondary bacterial infection may lead to the development of a pyocele. Mucocele with superimposed fungal infection is very rare. Only four cases have been reported in the literature, of which, two were allergic fungal sinusitis. It is very difficult to distinguish mucocele from fungal sinusitis, when etiher one is presented as a sinus mass, with radiologic findings alone. Only intraoperative and pathologic findings can tell the difference between the two diseases. Recently we experienced an anterior ethmoid mucocele which was treated with endoscopic sinus surgery and verified it histopatologically to be fungal sinusitis.

A Case of Extramedullary Plasmacytoma of the Larynx / 대한이비인후과학회지

Plasma cell neoplasm is an abnormal condition with an excessive proliferation of plasma cell in the reticuloendothelial tissue, Willis classified clinical and pathological features of plasma cell neoplasm into multiple myeloma, solitary plasmacytoma and extramedullary plasmacytoma. The extramedullary plasmacytoma is an unusual form of plasma cell neoplasm and occurs most commonly in the head and neck area, especially in the upper respiratory tract and oral cavity, where the most frequent sites are the paranasal sinuses, nasal cavity and nasopharynx. However, the larynx is rarely involved. In this study, we report, with a review of literatures, a case of extramedullary plasmacytoma of the larynx which was treated surgically.

A Case of Subtentorial Subdural Empyema Resulting from Chronic Otitis Media with Cholesteatoma / 대한이비인후과학회지

The subdural empyema is a rare disease characterized by a collection of pus in the subdural space. It usually occurs as a complication of otolaryngologic infections such as paranasal sinusitis, otitis media or mastoiditis. Although pus may localize anywhere in the subdural space, more than 90% of cases occur supratentorially. Infratentorial subdural empyema is rare, most of them otogenic, but subtentorially localized empyema is even rarer. It is considered as a neurosurgical emergency, but some authors have reported successful treatment of subdural empyema with conservative treatment. We have experienced a case of subtentorial subdural empyema resuting from chronic otitis media with cholesteatoma which was successfully treated with mastoidectomy, accompanied by the conservative treatment. In this paper, we report this case with a review of literature.