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Biomedical subjects

Y J Shin

Publications and source records attributed to Y J Shin.

At least 19 recordsLinked to original sources

Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells.

AIMS/HYPOTHESIS: We recently reported that expression of the gene encoding clusterin (Clu) is upregulated in the regenerating pancreas, particularly in tissues undergoing differentiation. This led us to propose that clusterin participates in the cytodifferentiation of pancreatic tissue, particularly the endocrine islet cells. The aim of this study was to investigate whether clusterin induces the differentiation of duct-lining cells into insulin-secreting cells. METHODS: We isolated ductal tissue from rat pancreas and cultured it to develop epithelial cell explants for transfection of the Clu cDNA as well as for treatment of clusterin protein. RESULTS: The number of newly differentiated insulin cells increased 6.9-fold upon Clu overexpression compared with controls. Ins1 mRNA and peptide levels were also increased. Furthermore, glucose-stimulated insulin secretion was observed in the differentiated insulin cells. These cells were immunoreactive for insulin and C-peptide, but negative for other islet hormones and for cytokeratin-20, which indicates a fully differentiated state. Insulin cell differentiation was also increased in a dose-dependent manner by treating duct cells in culture with clusterin, indicating a growth-factor-like action of clusterin in insulin cell differentiation. CONCLUSIONS/INTERPRETATION: These results suggest that clusterin can be considered as a potential morphogenic factor that promotes differentiation of pancreatic beta cells.

Animals↗

Rubella antibody loss rates in Korean children.

We followed students in eight elementary schools for rubella antibody from 1993 to 1996 (602 pairs) and 1996-9 (588 pairs) in Gyeonggi Province, Korea. We tested rubella IgG and administered rubella vaccine to the children with the titres < 10 IU/ml. The loss rates of rubella IgG during the follow-up periods were 14.3 and 15.8%, respectively. Among vaccinated groups, the loss rate was 18.8%, which was significantly higher than 13.8% of the mixture of natural and vaccine-induced immunity groups. The group that had the lower preceding antibody titre had a higher loss rate of 24.8% compared to 7.2% for the group whose titre was 40 IU/ml or above. In a multivariate analysis, age and gender were not related to antibody loss rate. Under this higher rubella antibody loss rate, in order to prevent congenital rubella syndrome, the immunization for women at childbearing age appears necessary until rubella can be eliminated or controlled.

Adult↗

Antisense Bcl2 oligonucleotide in cisplatin-resistant bladder cancer cell lines.

OBJECTIVE: To determine the change of expression of Bcl2 in cisplatin-resistant bladder cancer cell lines and the reversibility of chemoresistance to cisplatin with antisense oligonucleotide against Bcl2, as higher expression of Bcl2 is associated with drug resistance in many different cancer cell lines. MATERIALS AND METHODS: In the cisplatin-resistant bladder tumour cell lines T24R1 and T24R2, the expression of Bcl2 was determined by reverse transcription-polymerase chain reaction and Western blot assay, and antisense oligonucleotide targeting of the Bcl2 coding sequence was administered with lipofectin. RESULTS: The expression of Bcl2 mRNA and protein was greater in T24R1 and T24R2 cells than in the parent T24 cells. Short-term exposure to cisplatin up-regulated Bcl2 mRNA and protein expression in parent T24 cells. Treatment with antisense oligonucleotide down-regulated Bcl2 protein expression and significantly enhanced the cytotoxicity of cisplatin. CONCLUSIONS: Up-regulation of Bcl2 protein expression might be one of the mechanisms of cisplatin resistance in bladder cancer cells, and antisense Bcl2 oligonucleotide may be helpful in chemotherapy for bladder cancer by reversing cisplatin resistance.

Antineoplastic Agents↗

New chiral crown ether stationary phase for the liquid chromatographic resolution of alpha-amino acid enantiomers.

A new chiral stationary phase (CSP) for the liquid chromatographic separation of enantiomers was prepared by bonding a novel enantiopure (diphenyl-substituted 1,1'-binaphthyl) crown ether to 5 microm silica gel. The resulting CSP was applied to the separation of the enantiomers of various natural and unnatural alpha-amino acids. All alpha-amino acids tested were resolved very well on the new CSP, with the exception of proline, which does not contain a primary amino group. The resolution of alpha-amino acid enantiomers on this new CSP was found to be dependent on the type and amounts of organic and acidic modifiers, and on column temperature.

Amino Acids↗

Clusterin expression during regeneration of pancreatic islet cells in streptozotocin-induced diabetic rats.

AIMS/HYPOTHESIS: Beta-cell regeneration has been reported after islet injury in an animal model for diabetes. Recently, we showed up-regulation of clusterin after islet injury and suggested that clusterin might be involved in cytoprotection and in the regeneration of islet cells. The aim of this study was to investigate the correlation of clusterin expression with islet regeneration and its effect on islet cell replication. METHODS: Streptozotocin was administrated to rats to induce various types of diabetes. Islet regeneration and clusterin expression were examined after islet injuries. Clusterin cDNA was transfected to MIN6 cells and their proliferation activity was measured by a [3H]thymidine-incorporation assay. RESULTS: A diabetogenic dose of streptozotocin injected in rats provoked an immediate degeneration of beta cells. In this model, islets showed increased clusterin expression with extensive proliferation of alpha cells but showed poor beta-cell replication. A subdiabetogenic dose of streptozotocin, however, led to the proliferation of beta cells with clusterin up-regulation. In streptozotocin-treated neonatal rats, up-regulation of clusterin was noted during beta-cell proliferation. In all experimental models, clusterin was expressed in alpha cells in close correlation with islet cell proliferation, higher transcription of insulin mRNA and MAPKs activation. Cell replication was increased by 31 % in the MIN6 cells transfected by the clusterin cDNA. CONCLUSION/INTERPRETATION: Up-regulation of clusterin in alpha cells might induce beta-cell proliferation and thus restore their population after islet injury. We suggest that clusterin could be considered as a growth factor-like molecule stimulating islet-cell proliferation by paracrine action.

Aging↗

Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin.

Three Korean girls with ethylmalonic encephalopathy, the first Asian cases, were identified. In all three cases, we observed slight improvement in motor functions, cognitive behaviours and chronic mucoid diarrhoea after treatment with riboflavin and/or coenzyme Q10 treatment. The precise pathogenesis of ethylmalonic encephalopathy has not been fully elucidated, but riboflavin treatment may be helpful.

Brain Diseases, Metabolic, Inborn↗

Sensorineural hearing loss and otosclerosis: a clinical and radiologic survey of 437 cases.

The aim of this study was to determine if a relationship exists between bone level thresholds and the extension of otosclerotic foci within the otic capsule. The study consisted of a retrospective case review in a university hospital. We included patients who underwent surgery for otosclerosis in our department and who had a CT scan prior to surgery. We analyzed the data charts and CT scans of 437 cases (386 patients). On CT scan, we distinguished patients with fenestral otosclerosis and/or with a pericochlear focus. A pericochlear focus could be extended (Group 2) or not (Group 1) to the cochlear endosteum. Data for Groups 1 and 2 were compared with those for the control group of all patients for whom CT scan showed no cochlear focus (Group 3). Of the 437 CT scans, 399 were positive (91.3%). An anterior focus was reported in 305 cases (69.8%), a footplate thickening in 21 cases (4.8%) and both anomalies were encountered in 60 cases (13.7%). A pericochlear focus was reported in 53 examinations. This focus was extended to the endosteum in 14 cases (26.4% of the pericochlear foci). In Group 1, preoperative air conduction (AC) thresholds were significantly lower than in the control group (p < 0.05). The air--bone gap was also significantly larger in Group 1 (p < 0.05). Bone conduction (BC) thresholds were lower in Group 1 than in the control group but the difference was not significant. In Group 2, preoperative AC thresholds were significantly lower than in the control group (p < 0.05). BC thresholds were also lower in Group 2 than in the control group and the difference was significant (p < 0.05). As a result of this study, we assume that there may be a relationship between bone level thresholds and the radiological extension of otosclerosis within the otic capsule.

Adult↗

Correlations between computed tomography findings and family history in otosclerotic patients.

BACKGROUND: Otosclerosis is a heritable disease affecting the otic capsule. Its genetics have been studied since the 19th century, but several issues remain controversial. OBJECTIVE: The goals of this study were to assess the prevalence of sporadic and familial forms of otosclerosis in a population of otosclerotic patients and to compare the radiologic findings between both groups. STUDY DESIGN AND SETTING: This retrospective study was conducted in a single institution. PATIENTS: This study included 211 patients operated on for otosclerosis. MAIN OUTCOME MEASURES: Clinical data, including pure tone audiograms, were available from patients' charts. A questionnaire assessing family history of otosclerosis and deafness was mailed to the otosclerotic patients. A relative was considered otosclerotic if surgery confirmed the disease. The family history was correlated with the computed tomography results. This examination was performed before surgery in all patients. RESULTS: A family history of otosclerosis was found in 24.2% of the patients. The radiologic findings differed between patients with a sporadic form of otosclerosis and those with a familial form. The lesions were more often detectable, bilateral, and severe in the familial forms (p < 0.05). CONCLUSION: These findings lead to the assumption that fenestral radiologic otosclerosis occurs more in sporadic forms, whereas more extensive lesions on computed tomography seem to indicate the familial forms. Hereditary forms demonstrated to be familial seem to lead to more severe disease. The search for a genome locus of otosclerosis may be enlightened by these findings.

Adult↗

[Reliability of CT scan in the diagnosis of conductive hearing loss with normal tympanic membrane].

The goal of this study was to assess the reliability of CT-Scan in the cases of conductive hearing losses with normal tympanic membrane. A computed tomography of the temporal bone (CT-Scan) has been performed in a prospective manner in all patients who underwent surgery for a conductive hearing loss with a normal tympanic membrane in our department. Out of 474 cases, 437 cases (92.2%) presented with otosclerosis. In 25 cases a minor malformation (5.3%) was found at surgery, and in 12 cases (2.5%), another diagnosis was made. Sensitivity of CT-Scan was 91.3% in otosclerosis and 57% in minor malformations. In 8.7% of cases, a superficial and beginning surgical focus was put in evidence whereas CT-Scan was normal. Theses cases represent infra-radiological cases of otosclerosis. In case of radiological otosclerosis, fenestral otosclerosis was found in 83.5% of the cases. CT-Scan was found specific on the operated and deaf side, but in 11.3% of the cases, a radiologic focus did not have a clinical consequence on the controlateral side. A radiological focus is not systematically responsible for a hearing loss. Finally, CT-Scan remains a reliable, sensitive and specific exam in the diagnosis of cases of conductive hearing losses with normal tympanic membrane.

Audiometry↗

[Ambulatory surgery of otosclerosis: retrospective study of 102 cases].

A retrospective study of 102 selected patients operated for otosclerosis (34 outpatient surgery, 68 hospitalised), having all of them the inclusion criteria of the ambulatory surgery, treated as outpatient in a traditional health sector or hospitalised, depending on their own choice, has been lead. We analysed the results of the pure tone audiometric tests two to six months after surgery. No significative difference was found between the two groups on audiometric results as for the postoperative complications. On the other side, it seems that young patients are more interested by the one-day surgery. The failure of the ambulatory surgery could be explained by the vertigo or dizziness per- or postoperatively. Finally, the evaluation of the cost-benefit shows that the ambulatory surgery in a traditional health sector could lead a budgetary saving policy. A saving way that will grow in a specialized sector devoted to the ambulatory practice.

Adult↗

Retinoic acid and its geometrical isomers block both growth and fusion of L6 myoblasts by modulating the expression of protein kinase A.

All-trans retinoic acid (RA) and its geometrical isomers, such as 9-cis RA, 13-cis RA, and 9,13-di-cis RA, strongly inhibited both growth and fusion of L6 myoblasts. However, illumination of white light diminished their inhibitory activity on membrane fusion with little effect on cell growth. During myogenic differentiation, the intracellular level of cAMP decreased whereas the total activity of protein kinase A as well as the protein level of its regulatory subunit Ialpha (RIalpha) and catalytic subunit (Calpha) increased. RAs raised the intracellular level of cAMP by over 3-fold, but decreased the total activity of protein kinase A. Like RAs, dibutyryl-cAMP inhibited myoblast fusion and reduced the expression of both RIalpha and Calpha subunits. These results suggest that RAs negatively modulate the differentiation of L6 myoblasts by increasing the intracellular level of cAMP, which may in turn down-regulate the expression of protein kinase A and hence its activity.

Animals↗

Overexpression of protein kinase C delta represses expression of proliferin in NIH3T3 cells that regulates cell proliferation.

Protein kinase C (PKC) delta is known to inhibit proliferation of many cell types. In this study we found that overexpression of PKCdelta reduced proliferation of NIH3T3 cells. To identify specific genes regulated by PKCdelta in regulation of cell proliferation, we used differential display-polymerase chain reaction in PKCdelta-overexpressing NIH3T3 cells and found that the expression of proliferin, a secreted protein known to stimulate cell proliferation, was significantly repressed. Transient transfection study indicated that the repression of proliferin expression was inversely proportional to the expression levels of PKCdelta. Addition of an anti-proliferin antibody to culture medium to neutralize the secreted proliferin decreased cell proliferation in a dose-dependent manner. Our results, therefore, suggest that overexpression of PKCdelta induces transcriptional repression of proliferin, thereby resulting in inhibition of cell proliferation.

3T3 Cells↗

Benefits of cochlear implantation in elderly patients.

Cochlear implantation in elderly patients is a questionable subject. The purpose of this study was to evaluate the procedure and its outcome, the postoperative course, and the audiologic and social benefits of cochlear implantation in this population. Twenty-seven patients older than 60 years were compared with a control group of 15 adult patients. This retrospective study analyzed data concerning the outcome of the procedure, postoperative course, postoperative orthophonic test results, and answers of a questionnaire assessing the changes in communication, perception, and social outcomes. The procedure was uneventful in both groups. Minor complications were not more frequent in elderly patients. Orthophonic test results were comparable in both groups. At 12 months, 83% of the elderly patients had an open-set speech discrimination score above 60%. The benefits of cochlear implantation in terms of the quality of life are not statistically different with younger patients. Cost-utility analysis might support these findings.

Adult↗

Pure sensorineural hearing loss and otosclerosis. An imaging case report.

Pure sensorineural hearing loss is not a rare finding in otological practice. Numerous aetiologies could be at the origin of such a deficit. However, otosclerosis is very rarely cited as a cause of pure sensorineural hearing loss. We present one such case of pure sensorineural hearing loss linked to otosclerosis in a 30-year old caucasian male and underline the high contribution of computed tomography to confirm such a diagnosis. Pure sensorineural hearing loss due to otosclerosis is a rare event and can be misdiagnosed. The clinical diagnosis of such a disease may be difficult. In these cases, CT-Scan is the exam of choice to confirm the diagnosis.

Adult↗

Effectiveness of conservative management of acoustic neuromas.

OBJECTIVE: The goal of this study was to assess the effectiveness of the conservative management in patients with acoustic neuroma (vestibular schwannoma). STUDY DESIGN: This retrospective study was performed in a university hospital. PATIENTS: Patients were selected for this wait-and-see policy on the basis of age, general condition, audiometric results, tumor size, and patient preference. The study group included 97 patients, 87 of whom had at least two neuroradiologic examinations. The mean age of this population was 63 years (29 to 89 years). The mean length of follow-up of this population was 31 months. Eighty-seven of these patients had at least two radiologic examinations (magnetic resonance imaging or computed tomography). The mean interval between the initial and follow-up radiologic examinations was 15 months. MAIN OUTCOME MEASURES: Tumor size was measured by use of two-dimensional data in all patients. The mean tumor size was 12 mm. The growth rate of the tumor was estimated by comparison of the results of the measurements from the initial and follow-up neuroradiologic examinations. RESULTS: Of the 97 patients studied, 6 patients required surgery and 6 required radiotherapy. Sixty patients (62%) were still being treated conservatively at the end of the study period. Three patients of 28 who were classified as candidates for hearing preservation surgery lost their candidacy during the observation period. The mean annual tumor growth rate was 1.52 mm/year. The tumor was stable in size in 36% of patients, regressed in 11% of patients, or grew in 53% of patients. The growth patterns of the acoustic neuroma fell into five categories: continuous growth in 15% of patients, negative growth in 5%, growth followed by negative growth in 40%, negative growth followed by growth in 20%, and no variation of tumor size in 20%. CONCLUSION: Conservative management of acoustic neuromas carries difficulties: long-term follow-up of the patients and unpredictability of the tumor growth pattern. A reliable and reproducible radiologic method for evaluating tumor size is of great importance.

Adult↗

Perfusion impairments in infantile autism on technetium-99m ethyl cysteinate dimer brain single-photon emission tomography: comparison with findings on magnetic resonance imaging.

The neuro-anatomical substrate of autism has been the subject of detailed investigation. Because previous studies have not demonstrated consistent and specific neuro-imaging findings in autism and most such studies have been performed in adults and school-aged children, we performed a retrospective review in young children in search of common functional and anatomical abnormalities with brain single-photon emission tomography (SPET) using technetium-99m ethyl cysteinate dimer (ECD) and correlative magnetic resonance imaging (MRI). The patient population was composed of 23 children aged 28-92 months (mean: 54 months) who met the diagnostic criteria of autism as defined in the DSM-IV and CARS. Brain SPET was performed after intravenous injection of 185-370 MBq of 99mTc-ECD using a brain-dedicated annular crystal gamma camera. MRI was performed in all patients, including T1, T2 axial and T1 sagittal sequences. SPET data were assessed visually. Twenty patients had abnormal SPET scans revealing focal areas of decreased perfusion. Decreased perfusion of the cerebellar hemisphere (20/23), thalami (19/23), basal ganglia (5/23) and posterior parietal (10/23) and temporal (7/23) areas were noted on brain SPET. By contrast all patients had normal MRI findings without evidence of abnormalities of the cerebellar vermis, cerebellar hemisphere, thalami, basal ganglia or parietotemporal cortex. In conclusion, extensive perfusion impairments involving the cerebellum, thalami and parietal cortex were found in this study. SPET may be more sensitive in reflecting the pathophysiology of autism than MRI. However, further studies are necessary to determine the significance of thalamic and parietal perfusion impairment in autism.

Autistic Disorder↗

Comparison of Korean-American adoptees and biological children of their adoptive parents: a pilot study.

This study compared a small group of Korean-American adoptees with their adoptive siblings who are biological children of the adoptive parents with respect to their psychosocial adjustment. Eighteen Korean-American adoptees were compared with nine biological children by a structured demographic, medical, clinical survey form and the Child Behavior Checklist-Parent Form (CBCL-P). The parents did not raise any more concerns about the adjustment of adopted children than their biological children. On the CBCL-P, the two groups did not differ significantly in competence T-scores, total behavioral problems, broad and T-scores and the total number of problem behaviors except for lower social competence in adopted children and a higher internalization score in biological children. In conclusion, the international adoptees, the Korean-American children have adjusted well during their early childhood after early adoption. Further studies employing a larger sample are warranted to better understand the international adoption practice.

Adolescent↗

Analysis of the precore and core promoter DNA sequence in liver tissues from patients with hepatocellular carcinoma.

To investigate the role of mutant hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC), 20 patients with HCC were studied for precore and core promoter mutations in tumorous and nontumorous tissues. The precore and core promoter region was amplified and analyzed by direct sequencing. Among the 20 tumorous and nontumorous tissues, precore mutant HBV was found in 12 (60%) and 18 (90%), respectively. Of the 12 tumorous tissues with precore mutant, nine tissues had a single mutation (1896) and one tissue had another single mutation (1899). The remaining two tissues had a double mutation (1896 and 1899). A single mutation (1896) and a single mutation (1899) were found in 11 and two of the 18 nontumorous tissues with precore mutant, respectively. Among 20 tumorous and nontumorous tissues, HBV with a C to T mutation at nucleotide (nt) 1846 was detected in six and eight, respectively, and was associated with the virus carrying a mutation (1896 or 1899) except in two tumorous tissues. Mutations at nt 1762 and 1764 in core promoter were observed in 16 (80%) tumorous tissues and 18 (90%) nontumorous tissues. Mutations in the precore and core promoter region were found frequently in nontumorous tissue and in tumorous tissue (18/20 and 12/20 in precore region, 18/20 and 16/20 in core promoter respectively). The high prevalence of precore and core promoter mutations in liver tissue from patients with HCC suggests that these mutations may contribute to the development of HCC.

Adult↗