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Biomedical subjects

Jae Young Choi

Publications and source records attributed to Jae Young Choi.

At least 37 records · Page 2Linked to original sources

Vestibular malformation in mice lacking Na-K-2Cl cotransporter 1 and expression of Na-K-2Cl cotransporter 1 in human vestibular end organs.

CONCLUSION: The Na-K-2Cl cotransporter-1 (NKCCl) may be essential for the maintenance and functioning of the vestibular morphology in mice and it is strongly expressed in human vestibular end organs. OBJECTIVE: NKCCl is a member of the cation-coupled chloride transporter which participates in salt transport and cell volume regulation in diverse tissues. NKCCl-deficient mice exhibit deafness, and show structural alterations in the cochlea. In addition to hearing loss, NKCCl-deficient mice show a shaker-waltzer behavior, which suggests a vestibular system defect. In this study we investigated the morphology of the vestibular system of NKCCl-deficient mice and also evaluated whether NKCCl mRNA and its protein are expressed in human vestibular end organs. MATERIAL AND METHODS: NKCCl-deficient and wild-type mice aged 4-5 weeks were sacrificed. Their heads were cut in the midsagittal plane, fixed and decalcified. For light microscopy, 5-microm sections were cut and stained with hematoxylin-eosin. Human vestibular end organs were harvested during acoustic tumor surgery via a translabyrinthine approach. Some of these end organs were used for total mRNA extraction and the remainder for immunostaining. Reverse transcriptase polymerase chain reaction and immunostaining were performed for NKCCl. RESULTS: The scala media of the cochleae of the NKCCl-deficient mice had collapsed but the bony labyrinth appeared unaffected. However, the semicircular canals (SCCs) were much smaller than those in the wild-type mice. Furthermore, the SCCs were completely missing in some NKCCl-deficient mice. NKCCl mRNA was expressed in both the human macula and crista ampullaris, and its protein was expressed mainly in the transitional and dark cell areas of the human crista ampullaris.

Animals↗

Anterior lumbar interbody fusion in patients with a previous discectomy: minimum 2-year follow-up.

OBJECTIVE: A retrospective review was conducted to determine the availability of anterior lumbar interbody fusion (ALIF) in selected patients who presented with recurrent lumbar disc herniation. METHODS: A total of 22 patients who underwent ALIF were studied clinically and radiographically. The patients were 11 men and 11 women, with a mean age of 46 years (range 23-60 years) at the time of ALIF. The mean follow-up duration was 35 months (range 30-42 months). The fused level at which the ALIF was performed was as follows: L3-L4 (1 patient), L4-L5 (14 patients), and L5-S1 (7 patients). Back pain, leg pain, and functional outcomes were measured both before surgery and at the last follow-up visit. Patient satisfaction index was also assessed. RESULTS: Leg pain, back pain, and functional status all demonstrated statistically significant improvements between preoperative and postoperative scores by 86%, 77%, and 82%, respectively (P < 0.001). Nineteen of 22 patients (86.3%) were satisfied with their clinical results. Solid fusion was found in all patients. CONCLUSIONS: The authors found ALIF to be an effective procedure with satisfactory clinical results in selected patients with a recurrent disc herniation in the lumbar spine.

Adult↗

Mastoid and epitympanic obliteration in canal wall up mastoidectomy for prevention of retraction pocket.

OBJECTIVE: To evaluate the surgical outcome in patients who have undergone mastoid and epitympanic obliteration technique. STUDY DESIGN: : Retrospective review. SETTING: Tertiary care referral center. PATIENTS: The study group included 151 patients with cholesteatoma who underwent mastoid and epitympanic obliteration technique. This technique was applied to cases who had a strong chance of recurrent retraction pocket and cholesteatoma formation, including those patients with an adhesive drum indicating poor eustachian tube function (n = 52) and patients with a destructive scutum (n = 68). Thirty-one patients had both an adhesive drum and a destructive scutum. INTERVENTION: The connection between the mastoid cavity and the middle ear was blocked by obliterating the epitympanum and antrum with bone pate and the remaining mastoid cavity with abdominal fat. MAIN OUTCOME MEASURES: The postoperative drum state, the incidence of retraction pocket formation and cholesteatoma recurrence, the surgical complications of obliteration, and the hearing outcome. RESULTS: In 114 of 151 patients (75.4%), the middle ear was well healed and well aerated. The retraction pocket formation or cholesteatoma recurrence did not develop in any subject. Postauricular skin depression was the most common complication of this technique (n = 31 [20.5%]). In three patients (2.0%), the bone pate used for obliteration was infected. Of the 56 cases who underwent a staged operation to regain their hearing, 37 resulted in a postoperative air-bone gap less than 20 dB hearing level. CONCLUSION: Mastoid and epitympanic obliteration is an effective option for preventing a retraction pocket and cholesteatoma recurrence in patients with a poorly functioning eustachian tube or a defective scutum, while preserving the same advantage of the canal wall up technique.

Adolescent↗

[Two cases of histopathologically advanced (stage IV) early gastric cancer].

Various minimally invasive surgical techniques in some cases of early gastric cancer are becoming common practice. However, there are rare cases of advanced cancer with distant metastasis although the invasion of the gastric wall is limited to the mucosa and/or submucosa (defined as early gastric cancer according to UICC-TNM classification). We report two cases of early gastric cancer with distant metastasis (stage IV). Both tumors were defined as early cancer because they were confined to the submucosa. One was a type IIa early cancer, histologically classifiable as a signet ring cell carcinoma (according to the Japanese Classification of Gastric Carcinoma and UICC-TNM classification); the other was a surface spreading type IIb + IIc, classifiable as a signet ring cell carcinoma, too. Stage IV factors were ovarian metastasis (Krukenberg tumor) in the former and N3 in the latter case.

Adult↗

Prostaglandin E2 induces MUC8 gene expression via a mechanism involving ERK MAPK/RSK1/cAMP response element binding protein activation in human airway epithelial cells.

MUC8 gene expression is overexpressed in nasal polyp epithelium and is also increased by treatment with inflammatory mediators in nasal epithelial cells. These data suggest that MUC8 may be one of important mucin genes expressed in human airway. However, the mechanisms of various inflammatory mediator-induced MUC8 gene expression in normal nasal epithelial cells remain unclear. We examined the mechanism by which prostaglandin E(2) (PGE2), an arachidonic acid metabolite, increases MUC8 gene expression levels. Here, we show that ERK mitogen-activated protein kinase is essential for PGE2-induced MUC8 gene expression in normal human nasal epithelial cells and that p90 ribosomal S 6 protein kinase 1 (RSK1) mediates the PGE2-induced phosphorylation of cAMP-response element binding protein. Our results also indicate that cAMP-response element at the -803 region of the MUC8 promoter is an important site of PGE2-induced MUC8 gene expression. In conclusion, this study gives insights into the molecular mechanism of PGE2-induced MUC8 gene expression in human airway epithelial cells.

Cell Line, Tumor↗

Membrane-specific expression of functional purinergic receptors in normal human nasal epithelial cells.

Extracellular purines and pyrimidines regulate various physiological responses via the cell surface receptors known as purinoreceptors and may exert autocrine or paracrine effects on ion transport, fluid transport, ciliary beat frequency, and mucin secretion. Therefore, this study aims to investigate the expression patterns of the purinoreceptors in normal human nasal epithelial (NHNE) cells. In RT-PCR, the mRNAs for several P2X (P2X3, P2X4, P2X7) and P2Y (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12) receptors were identified in NHNE cells. Functional localizations of P2 receptors were investigated by measuring intracellular calcium concentration ([Ca2+]i) increases in membrane-specific manner using a double-perfusion chamber. Absence of the responses of alphabeta-methylene ATP and 2-methylthio-ATP excluded functionally active P2X3, P2X4, and P2Y1 receptors as far as [Ca2+]i increase is concerned. Applications with ATP and UTP revealed that luminal membranes of NHNE cells express P2Y2 and P2Y6 receptors and basolateral membranes express P2Y2 receptor. Expressions of P2Y2 and P2Y6 receptors in NHNE cells were further verified by immunoblotting using specific antibodies. In addition, the results with 2,3-O-(4-benzoyl)-benzoyl-ATP indicate that the P2Y11 receptor may be present on the luminal side. In conclusion, the NHNE cells express functionally active P2Y2, P2Y6, and P2Y11 receptors in a membrane-specific pattern, which may play an important role in the control of mucin and fluid secretion in NHNE cells.

Base Sequence↗

Purinergic stimulation induces Ca2+-dependent activation of Na+-K+-2Cl- cotransporter in human nasal epithelia.

Increasing evidence suggests that P2 receptors (P2Rs) in airway epithelial cells perform critical functions in auto- or paracrine regulation of fluid and mucus secretion. In the present study, we characterized the effects of P2R stimulation on Na(+)-K(+)-2Cl(-) cotransporter (NKCC) activity in normal human nasal epithelial (NHNE) cells. [Ca(2+)](i) and pH(i) were measured in primary cultures of NHNE cells using a double perfusion chamber, which enabled us to analyze membrane-specific transporter activities. NKCC activities were estimated by the pH(i) reduction due to Na(+)-dependent and bumetanide-sensitive intracellular uptake of NH(4)(+). NKCC activities were observed in the basolateral membrane, but not in the luminal membrane, of NHNE cells. Interestingly, P2Rs were expressed in both membranes, and the stimulation of either luminal or basolateral P2R increased NKCC activity. Blockades of luminal Cl(-) channels, basolateral K(+) channels, or protein kinase C did not affect the activation of NKCC by basolateral P2R stimulation. The effects of luminal P2R stimulation were partially reduced by Cl(-) channel blockers. However, chelation of intracellular Ca(2+) by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) treatment completely blocked the stimulatory effects of luminal and basolateral P2Rs on NKCC. In addition, increasing [Ca(2+)](i) by treatment with ionomycin-stimulated NKCC activity. These results provide evidence that stimulation of P2Rs directly activates basolateral NKCC by Ca(2+)-dependent pathways in NHNE cells, which is an important aspect of the purinergic regulation of ion and fluid secretions in human airway epithelia under physiologic and pathologic conditions.

Calcium↗

All-trans retinoic acid induces mucociliary differentiation in a human cholesteatoma epithelial cell culture.

OBJECTIVES: Retinoic acid (RA) can prevent keratin formation and induce mucous differentiation in epithelia. In this study, we attempted to induce keratinizing squamous epithelium from human cholesteatoma epithelial (HCE) cells using an air-liquid interface (ALI) technique. We also examined the effect of RA on the phenotype of keratinizing HCE cells. MATERIAL AND METHODS: HCE cells were cultured in RA-free defined media at an ALI or in a submerged state. We examined the morphological differences between ALI and submerged cultures, and histologically investigated the changes of phenotype after RA treatment. We also determined the effect of RA on the mRNA expressions of the cornifin-alpha and mucin genes as indicators of squamous and mucous differentiation, respectively. RESULTS: Using an ALI technique, we were able to differentiate HCE cells into a keratinizing squamous epithelium. When we treated the keratinizing HCE cells with RA, the morphological phenotype progressively changed into mucociliary epithelium. In addition, the expression of cornifin-alpha mRNA was suppressed, and the expressions of mucin gene 5AC (MUC5AC) and MUC5B mRNA increased progressively with RA treatment. CONCLUSION: We successfully developed a culturing system for keratinizing differentiation of HCE cells using the ALI technique in a defined medium. Our study also clearly showed that RA treatment led to mucociliary differentiation of HCE cells.

Cell Differentiation↗

A retrospective study of the clinical outcomes and significant variables in the surgical treatment of temporal lobe tumor associated with intractable seizures.

A retrospective study was performed assessing the preoperative evaluation, and the postoperative outcomes in 35 patients with a temporal lobe tumor with intractable seizures who were treated by our neurosurgery service between October 1995 and December 1999. The mean age of the patients at the time of surgery was 27.9 years. The period of follow-up after surgery was a mean of 33.0 months. Of the study group of 35 patients, 27 (77.1%) became completely seizure free after surgery (class I), and 2 patients (5.7%) had no more than 2 seizures per year (class II). Worthwhile seizure control was achieved in 29 patients (82.8%). There was a statistical significance between the extent of tumor resection and favorable seizure outcome (p = 0.014). The most frequent histopathological diagnoses were classic epilepsy-associated ganglioglioma in 16 (45.7%) patients and low-grade astrocytoma in 10 (28.6%) patients. Complete resection of tumor was the most significant factor in obtaining a favorable seizure outcome.

Adolescent↗

Expression of a recombinant Cry1Ac crystal protein fused with a green fluorescent protein in Bacillus thuringiensis subsp. kurstaki Cry-B.

To investigate the co-expression and crystallization of a fusion gene between the Bacillus thuringiensis crystal protein and a foreign protein in B. thuringiensis, the expression of the Cry1Ac fused with green fluorescent protein (GFP) genes in a B. thuringiensis Cry(-)B strain was examined. The cry1Ac gene was cloned in the B. thuringiensis-E. coli shuttle vector, pHT3101, under the control of the native cry1Ac gene promoter, while the GFP gene was inserted into the XhoI site upstream of the proteolytic cleavage site, in the middle region of the cry1Ac gene (pProAc-GFP). The B. thuringiensis Cry(-)B strain carrying pProAc-GFP (ProAc-GFP/CB) did not produce any inclusion bodies. However, the transformed strain expressed fusion protein forms although the expression level was relatively low. Furthermore, an immunoblot analysis using GFP and Cry1Ac antibodies showed that the fusion protein was not a single species, but rather multiple forms. In addition, the N-terminal fragment of Cry1Ac and a non-fused GFP were also found in the B. thuringiensis Cry(-)B strain after autolysis. The sporulated cells before autolysis and the spore-crystal mixture after autolysis of ProAc-GFP/CB exhibited insecticidal activities against Plutella xylostella larvae. Accordingly, the current results suggest that a fusion crystal protein produced by the transfomant, ProAc-GFP/CB, can be functionally expressed but easily degraded in B. thuringiensis.

Animals↗

Radiological and hormonal responses of functioning pituitary adenomas after gamma knife radiosurgery.

In this study, we examined patients with functioning pituitary adenoma that underwent Gamma Knife radiosurgery (GKS). In particular, we assessed the effects of GKS on the growth and endocrinological response of the functioning pituitary adenoma. Forty-two cases of functioning pituitary adenoma treated with GKS were analyzed. The mean follow-up duration was 42.5 months (range 6 - 98), and the mean tumor volume was 1.4 cm(3) (range 0.1 - 3.8). Multiple isocenters, ranging from 1 to 6 in number (mean 2.7), were used. The tumor margin was covered by an isodose ranging from 50 to 90%. The margin dose was 18 to 40 Gy (mean 28.5) and the maximum dose varied from 35 to 80 Gy (mean 54.1). Tumor growth was controlled in 96.9% of the cases and tumor shrinkage occurred in 40.6% of the cases. Hormonal response was observed in 35 of the 42 (83.3%) patients after GKS, with a mean duration of 6.8 months. Sixteen of the 42 (38.1%) patients showed hormonal normalization, with a mean duration of 21 months. In our multivariate analysis, high integral dosage (p=0.005) and maximum dosage (p=0.001) correlated significantly with hormonal normalization. For patients with functioning pituitary adenoma, GKS can be effective in controlling tumor growth and inducing hormonal normalization, especially if patients are reluctant to undergo surgical resection, or are not able to undergo microsurgery under general anesthesia. It appears that early hormonal normalization can be induced by high maximum dosage (at least 50 Gy) and broad coverage of the target volume within the isodose curve, while keeping the maximum dose to the visual pathways below 9 Gy.

Adenoma↗

Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells.

Mucin hypersecretion is commonly observed in many inflammatory diseases of the respiratory tract. MUC5AC is generally recognized to be a major airway mucin because MUC5AC is highly expressed in the goblet cells of human airway epithelium. Moreover, it is regulated by various inflammatory cytokines. However, the mechanisms by which the interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha induce MUC5AC gene expression in normal nasal epithelial cells, and the signal molecules involved, especially in the downstream signaling of mitogen-activated protein (MAP) kinases, remain unclear. Here we show that pharmacologic or genetic inhibition of either ERK or p38 MAP kinase pathway abolished IL-1beta- and TNF-alpha-induced MUC5AC gene expression in normal human nasal epithelial cells. Our results also indicate that the activation of mitogen- and stress-activated protein kinase 1 (MSK1) and cAMP-response element-binding protein and cAMP-response element signaling cascades via ERK and p38 MAP kinases are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression. Taken together, these studies give additional insights into the molecular mechanism of IL-1beta- and TNF-alpha-induced MUC5AC gene expression and enhance our understanding on mucin hypersecretion during inflammation.

Cell Line↗

An improved baculovirus insecticide producing occlusion bodies that contain Bacillus thuringiensis insect toxin.

Baculovirus occlusion bodies, large proteinaceous structures which contain virions, have recently been engineered to incorporate foreign proteins. The major constituent protein of occlusion bodies from the baculovirus Autographa californica nucleopolyhedrovirus is polyhedrin, and assembly of recombinant occlusion bodies which incorporate a foreign protein depends on an interaction between native polyhedrin and a polyhedrin-foreign protein fusion. This technology has now been applied to the generation of a recombinant baculovirus (ColorBtrus) that produces occlusion bodies incorporating the Bacillus thuringiensis (Bt) insecticidal Cry1Ac toxin protein. ColorBtrus coexpresses native polyhedrin and a fusion protein in which polyhedrin is fused to the Bt toxin, which is in turn fused to green fluorescent protein (GFP). Analysis of ColorBtrus occlusion bodies confirmed that they include both Bt toxin and GFP, yet still incorporate virions. Bioassay of ColorBtrus demonstrated that its speed of action and pathogenicity are strikingly enhanced compared to wild-type virus. ColorBtrus represents a novel, powerful biological insecticide that combines positive attributes of both Bt toxin and baculovirus based systems.

Animals↗

Uridine-5'-triphosphate and adenosine triphosphate gammaS induce mucin secretion via Ca2+-dependent pathways in human nasal epithelial cells.

OBJECTIVES: Nucleotides such as adenosine triphosphate (ATP) and uridine-5'-triphosphate (UTP) play fundamental roles in the early stage of secretion in nasal epithelial cells via the P2Y receptor. In this study, we examined the expression pattern of P2Y subtypes and their functions on Ca2+ influx ([Ca2+]i) in normal human nasal epithelial (NHNE) cells. We also examined the effect of UTP (an agonist for P2Y2) and ATPgammaS (an agonist for P2Y11) on mucin secretion and mucin gene expression. MATERIAL AND METHODS: The expression pattern of P2Y receptors and the mRNA levels of MUC5AC, MUC5B and MUC8 were examined after treatment with UTP and ATPgammaS by means of reverse transcriptase polymerase chain reaction. Mucin was quantified by an immunoblotting assay. We measured [Ca2+]i in NHNE cells using a double perfusion chamber. RESULTS: Two uracil-sensitive receptors (P2Y2, P2Y4) and two adenine-selective receptors (P2Y1, P2Y11) were expressed in NHNE cells. UTP and ATPgammaS increased [Ca2+]i via caffeine-sensitive pathways, and these two agonists stimulated mucin secretion to a similar magnitude without their gene enhancement. In addition, the mucin stimulatory effects subsided when the intracellular Ca2+ was removed by 2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. CONCLUSION: This study showed that P2Y2 and P2Y11 receptors were expressed in NHNE cells and that their agonists, UTP and ATPgammaS, act as secretogogues on mucin secretion via Ca2+-dependent pathways.

Adenosine Triphosphate↗

Effect of uridine 5'-triphosphate on mucin and lysozyme expression in human middle ear epithelial cells.

OBJECTIVE: Extracellular uridine 5'-triphosphate (UTP) regulates a variety of biological functions in the airway epithelium, including chloride and fluid transport, mucociliary clearance and mucin secretion via the P2Y purinergic receptors. This study was undertaken to investigate which P2Y purinergic receptors are expressed in normal human middle ear epithelial (NHMEE) cells. We also determined the levels of mucin and lysozyme secretion and their mRNA expressions following stimulation with UTP in passage-2 cultured NHMEE cells. MATERIAL AND METHODS: An immunoblotting assay was performed for quantitation of mucin and lysozyme proteins and RT-PCR for their gene levels after treatment with UTP was done in normal human middle ear epithelial cells. RESULTS: Middle ear epithelial cells expressed P2Y1, P2Y2, P2Y6, P2Y11, and P2Y12 receptors but not P2Y4 receptor. Apically applied UTP induced increased mucin and lysozyme secretion, as measured by dot blotting. In contrast, UTP did not enhance mucin and lysozyme mRNA expression until 72 h after treatment. CONCLUSION: This study suggests that UTP acts as a secretogogue on mucin and lysozyme secretion in NHMEE cells via the P2Y2 and/or P2Y6 receptor.

Cells, Cultured↗

Retinoic acid depletion induces keratinizing squamous differentiation in human middle ear epithelial cell cultures.

OBJECTIVE: The pathogenesis of cholesteatoma behind an intact tympanic membrane remains controversial. Squamous metaplasia of the middle ear mucosa is thought to be a possible mechanism in such cases. However, to date, no definitive experimental results have proved this association. This study was undertaken to investigate whether normal human middle ear epithelial (NHMEE) cells undergo keratinizing squamous differentiation in a retinoic acid (RA)-deficient culture. MATERIAL AND METHODS: We examined the morphological differences between RA-deficient and -sufficient cultures, and determined the expressions of the mucin gene and cornifin-alpha mRNAs as indicators of mucous and squamous differentiation, respectively. RESULTS: Histomorphologically, the NHMEE cells differentiated into a keratinizing squamous epithelium in RA-deficient cultures. In addition, the expressions of mucin gene 5AC (MUCSAC) and MUC8 mRNAs were suppressed, and the expression of cornifin-alpha mRNA increased progressively as a function of differentiation in RA-deficient cultures. CONCLUSIONS: This study shows that RA depletion induces keratinizing squamous differentiation in NHMEE cell cultures. This finding supports the hypothesis that middle ear cholesteatoma originates from metaplastic middle ear mucosa.

Cell Differentiation↗

Mode of parotid involvement in external auditory canal carcinoma.

Until now, little was known about the mode of parotid involvement in external auditory canal (EAC) carcinoma. The incidence of parotid node metastasis and direct parotid invasion was examined in patients with EAC carcinoma. The study comprised 11 patients with squamous cell carcinomas (SCC) and 10 patients with adenoid cystic carcinomas (ACC). A retrospective review of the surgical specimens was undertaken with specific reference to parotid node metastasis and parotid invasion. Parotid node metastasis was noted only in two cases of advanced staged SCC, whereas none of the ACC patients showed parotid node metastasis. Direct parotid invasion occurred only in advanced staged SCC, however, it did occur in early stage ACC. Our data indicated that elective parotidectomy for control of occult parotid node metastasis is necessary only in advanced SCC carcinoma, whereas parotid management to secure adequate safety margins is mandatory for advanced SCC and all cases of ACC.

Adult↗

Chronic epidural hematoma with rapid ossification.

CASE REPORT: The authors present a rare case of ossified chronic epidural hematoma. A 13-year-old female patient presented with an ossified chronic epidural hematoma. She had sustained a head injury about 10 weeks previously and had received conservative care for a delayed-onset epidural hematoma at a local hospital. Ossification was identified about 4 weeks after the head injury and then progressed rapidly. A chronic epidural hematoma with a thick collagenous capsule and newly formed bone was removed 73 days after the head injury. CONCLUSION: An epidural hematoma with mild symptoms can be treated conservatively. When, however, the hematoma is observed not to be naturally absorbed during serial follow-up examinations, surgical removal must be considered, even if the patient's condition is good, because this entity carries the risk of bone calcification and ossification.

Adolescent↗