Search PubMed⌕ Search

Biomedical subjects

C C Lee

Publications and source records attributed to C C Lee.

At least 199 records · Page 11Linked to original sources
PubMed1999

Long-distance PCR-based screening for large rearrangements of the LDL receptor gene in Korean patients with familial hypercholesterolemia.

BACKGROUND: The LDL receptor is a cell-surface protein that regulates plasma cholesterol by specific uptake of LDL particles from the blood circulation. Familial hypercholesterolemia (FH) results from defective catabolism of LDL, which is caused by mutations in the LDL-receptor gene. METHODS: For the rapid and reliable detection of large rearrangements in the LDL-receptor gene, we established a screening method based on long-distance PCR as an alternative to Southern-blot hybridization. Using long-distance PCR, 45 unrelated Korean subjects heterozygous for FH were screened to assess the frequency and nature of major structural rearrangements in the LDL-receptor gene. RESULTS: Two different deletion mutations, FH6 (same type as FH3 and FH311) and FH 32, were detected in four families by long-distance PCR. Detailed restriction mapping and sequence analysis showed that FH6 was a 5.71-kb deletion extending from intron 8 to intron 12 and that FH32 was a 2-kb deletion extending from intron 6 to intron 7. Sequence analysis for the breakpoints of all deletions detected in Korean FH patients showed that only the left arms of the Alu repetitive sequences were involved in the deletion event. CONCLUSIONS: The screening method based on long-distance PCR provides a powerful strategy for the detection of large rearrangements in the LDL-receptor gene and is a rapid and reliable screening alternative to Southern-blot hybridization.

Base Sequence↗
PubMed1999

Prenatal diagnosis of thoracopelvic dysplasia. A case report.

BACKGROUND: Thoracopelvic dysplasia, a variant of asphyxiating thoracic dysplasia (Jeune syndrome), is an uncommon skeletal disorder characterized by a small thorax, pelvic abnormalities and other complex, combined anomalies, including hypomelia, polydactyly and renal anomalies. CASE: A 32-year-old woman, gravida 1, para 0, was referred at 27 weeks' gestation due to polyhydramnios. Sonography revealed hydramnios, low fetal thoracic circumference (TC) and abdominal circumference (AC) ratio (0.78), skull and skin edema, increased nuchal translucency (7 mm), micrognathia, low-set ears, left cardiac deviation (66 degrees), overriding fingers, and club and rock-buttock feet. Amniocentesis revealed a normal karyotype (46, XY). Asphyxiating thoracic dysplasia was considered. At 40 weeks' gestation, a male infant was delivered vaginally. Besides the prenatal findings, cryptorchidism and high-arched palate were noted. Radiography of the infant revealed a narrow, funnel-shaped thorax and small pelvis with short, flared iliac bones; poorly developed acetabulum; and small, shallow sciatic notch. No dyspnea was observed at five months postpartum. CONCLUSION: Thoracopelvic dysplasia should be considered when a low TC/AC ratio (< 0.8) is observed. In this case the final diagnosis was made after detailed exclusion of other disorders combined with observation of a small thorax. Prenatal diagnosis of thoracopelvic dysplasia is possible.

Adult↗
PubMed1999

Atypical central neurocytoma: report of a case.

Central neurocytomas are rare, relatively benign intraventricular neoplasms composed of uniform round cells with neuronal differentiation. The majority of previously reported central neurocytomas did not recurr after tumor removal and the patients had favorable postoperative outcomes. Only a few cases with malignant histopathology or malignant behavior have been noted. Atypical central neurocytoma is a new entity that was first described in the literature in 1997. The tumors have been noted to exhibit a Ki-67 labeling index of 2% or more, or vascular proliferation, mitoses, and necrosis, or both. Atypical histologic findings are usually associated with a somewhat less favorable clinical course and requires postoperative radiotherapy. We report a unique case of a 33-year-old man with a large intraventricular central neurocytoma. The characteristic histopathologic picture, the immunoreactivity for both synaptophysin and neuron-specific enolase, and the ultrastructural features of neuronal differentiation distinguished it from ependymoma and oligodendroglioma. The mitotic activity (up to 3 mitoses/10 high power field) and the high percentage of Ki-67-staining tumor cells (labeling index, 5.0%) in our case were consistent with the atypical variant of central neurocytoma. The patient underwent craniotomy and partial resection of the tumor. Unfortunately, he died of hydrocephalus and brain edema, the next day.

Adult↗
PubMed1999

Assessment of functional MR imaging in neurosurgical planning.

BACKGROUND AND PURPOSE: Presurgical sensorimotor mapping with functional MR imaging is gaining acceptance in clinical practice; however, to our knowledge, its therapeutic efficacy has not been assessed in a sizable group of patients. Our goal was to identify how preoperative sensorimotor functional studies were used to guide the treatment of neuro-oncologic and epilepsy surgery patients. METHODS: We retrospectively reviewed the medical records of 46 patients who had undergone preoperative sensorimotor functional MR imaging to document how often and in what ways the imaging studies had influenced their management. Clinical management decisions were grouped into three categories: for assessing the feasibility of surgical resection, for surgical planning, and for selecting patients for invasive functional mapping procedures. RESULTS: Functional MR imaging studies successfully identified the functional central sulcus ipsilateral to the abnormality in 32 of the 46 patients, and these 32 patients are the focus of this report. In epilepsy surgery candidates, the functional MR imaging results were used to determine in part the feasibility of a proposed surgical resection in 70% of patients, to aid in surgical planning in 43%, and to select patients for invasive surgical functional mapping in 52%. In tumor patients, the functional MR imaging results were used to determine in part the feasibility of surgical resection in 55%, to aid in surgical planning in 22%, and to select patients for invasive surgical functional mapping in 78%. Overall, functional MR imaging studies were used in one or more of the three clinical decision-making categories in 89% of tumor patients and 91% of epilepsy surgery patients. CONCLUSION: Preoperative functional MR imaging is useful to clinicians at three key stages in the preoperative clinical management paradigm of a substantial percentage of patients who are being considered for resective tumor or epilepsy surgery.

Adolescent↗
PubMed1999

Prenatal diagnosis of partial trisomy 3p(3p23-->pter) and monosomy 7q(7q36-->qter) in a fetus with microcephaly alobar holoprosencephaly and cyclopia.

We report the prenatal diagnosis of partial trisomy 3p(3p23-->pter) and monosomy 7q(7q36-->qter) in a fetus with microcephaly, alobar holoprosencephaly and cyclopia. A 26-year-old primigravida woman was referred for genetic counselling at 23 gestational weeks due to sonographic findings of intra-uterine growth retardation and cranio-facial abnormalities. Level II ultrasonograms further demonstrated alobar holoprosencephaly, a proboscis above the eye and a single median orbit consistent with cyclopia. Genetic analysis and fluorescence in situ hybridization on cells obtained from amniocentesis showed distal 3p trisomy (3p23-->pter) and 7q36 deletion, 46,XX,der(7)t(3;7)(p23;q36), resulting from a paternal t(3;7) reciprocal translocation. The pregnancy was terminated. Autopsy further confirmed the presence of arrhinencephaly, agenesis of the corpus callosum and a single ventricle of the brain. The phenotype of this antenatally diagnosed case is compared with those observed in 10 previously reported cases with simultaneous occurrence of partial trisomy 3p and terminal deletion 7q. All cases are associated with severe forms of holoprosencephaly and facial dysmorphism. This delineates an autosomal imbalance syndrome or a dosage effect involving duplication of distal 3p/deficiency of terminal 7q and dysmorphogenesis of the forebrain and mid-face.

Abnormalities, Multiple↗
PubMed1998

Association between apolipoprotein(a) polymorphism and Lp(a) levels in Koreans.

In view of the clinical importance of lipoprotein(a) [(Lp(a)] in coronary artery disease (CAD), we investigated the apo(a) size polymorphism, sequence polymorphisms of five base repeats [(TTTTA)n] in the noncoding region, and of Met/Thr in the coding region of the apolipoprotein(a) [apo(a)] gene. The apo(a) polymorphisms were examined in 184 Korean patients with CAD and 121 healthy subjects. In size polymorphism, there was an inverse association between plasma Lp(a) levels and the apo(a) isoforms in the CAD group (p < 0.005). For (TTTTA)n sequence polymorphism, subjects with the 8/8 genotype were most frequently observed in the two groups. Plasma Lp(a) levels showed a significant difference between the 8/5 versus the 8/8 genotype in the CAD group. On the other hand, Lp(a) levels varied significantly among the genotypes of a Met/Thr polymorphism in normal controls (P < 0.01). The heterozygous genotype had an intermediate level of Lp(a) between the two homozygous genotypes, thereby showing gene dosage effect. Thus, it is possible that the apo(a) polymorphisms are responsible for variations in the Lp(a) levels.

Adult↗
PubMed1998

Is there really an NPY Y3 receptor?

NPY is an abundant neuropeptide that is widely distributed throughout the central and peripheral nervous systems. Based on pharmacological and cloning data, there are believed to be six different types of NPY receptors. The Y3 receptor is the only one of the six that has not been cloned or well characterized. Y3 receptors have been shown to be important in the regulation of visceral afferents within the nucleus tractus solitarius (NTS). In the present experiments, we have compared the effects of NPY and various analogs on Ba2+ currents in acutely dissociated neurons from the NTS and the neighboring area postrema (AP). No neurons from either NTS or AP responded to [D-Trp32]NPY suggesting that these areas lack Y5 receptors. However, we found a group of NTS neurons that only responded to NPY and not PYY or any other analogs. This agonist profile corresponds to that described for NPY Y3 receptors. No AP neurons showed this type of agonist profile. Other neurons responded to a variety of NPY analogs indicating the presence of Y1, Y2, and Y4 receptors in both nuclei.

Animals↗
PubMed1998

DNA binding by the KP repressor protein inhibits P-element transposase activity in vitro.

P elements are a family of mobile DNA elements found in Drosophila. P-element transposition is tightly regulated, and P-element-encoded repressor proteins are responsible for inhibiting transposition in vivo. To investigate the molecular mechanisms by which one of these repressors, the KP protein, inhibits transposition, a variety of mutant KP proteins were prepared and tested for their biochemical activities. The repressor activities of the wild-type and mutant KP proteins were tested in vitro using several different assays for P-element transposase activity. These studies indicate that the site-specific DNA-binding activity of the KP protein is essential for repressing transposase activity. The DNA-binding domain of the KP repressor protein is also shared with the transposase protein and resides in the N-terminal 88 amino acids. Within this region, there is a C2HC putative metal-binding motif that is required for site-specific DNA binding. In vitro the KP protein inhibits transposition by competing with the transposase enzyme for DNA-binding sites near the P-element termini.

Amino Acid Sequence↗
PubMed1998

Changes in mitochondrial function resulting from synaptic activity in the rat hippocampal slice.

Digital imaging microfluorimetry was used to visualize changes in mitochondrial potential and intracellular Ca2+ concentration, [Ca2+]i, in thick slices of rat hippocampus. Electrical activity, especially stimulus train-induced bursting (STIB) activity, produced slow, prolonged changes in mitochondrial potential within hippocampal slices as revealed by fluorescence measurements with rhodamine dyes. Changes in mitochondrial potential showed both temporal and spatial correlations with the intensity of the electrical activity. Patterned changes in mitochondrial potential were observed to last from tens of seconds to minutes as the consequence of epileptiform discharges. STIB-associated elevations in [Ca2+]i were also prolonged and exhibited a spatial pattern similar to that of the mitochondrial depolarization. The mitochondrial depolarization was sensitive to TTX and glutamate receptor blockers ([Mg2+]o and CNQX or DNQX plus D-AP-5) and to the inhibition of glutamate release by activation of presynaptic NPY receptors. The monitoring of mitochondrial potential in slice preparations provides a new tool for mapping synaptic activity in the brain and for determining the roles of mitochondria in regulation of brain synaptic activity.

Animals↗
PubMed1998

ErbB2 expression increases the spectrum and potency of ligand-mediated signal transduction through ErbB4.

Interleukin 3-dependent murine 32D cells do not detectably express members of the ErbB receptor family and do not proliferate in response to known ligands for these receptors. 32D transfectants were generated expressing human ErbB4 alone (32D.E4) or with ErbB2 (32D.E2/E4). Epidermal growth factor (EGF), neuregulin 1-beta (NRG1-beta), betacellulin (BTC), transforming growth factor-alpha (TGF-alpha), heparin binding-EGF (HB-EGF), and amphiregulin were analyzed for their ability to mediate mitogenesis in these transfectants. 32D.E4 responded mitogenically to NRG1-beta and BTC. Surprisingly, EGF also induced significant DNA synthesis and TGF-alpha was negligibly mitogenic on 32D.E4 cells, whereas HB-EGF and amphiregulin were inactive. Although coexpression of ErbB2 with ErbB4 in 32D.E2/E4 cells did not significantly alter DNA synthesis in response to NRG1-beta or BTC, it greatly enhanced mitogenesis elicited by EGF and TGF-alpha and unmasked the ability of HB-EGF to induce proliferation. EGF-related ligands that exhibited potent mitogenic activity on 32D.E2/E4 cells at low concentrations induced adherence, morphological alterations, and up-regulation of the Mac-1 integrin and FcgammaRII/III at higher concentrations. While 125I-EGF could be specifically crosslinked to both 32D.E4 and 32D.E2/E4 cells, its crosslinking capacity was greatly enhanced in the cotransfected cells. The ability of the various ligands to mediate proliferation and/or adhesion in the two transfectants correlated with their capacity to induce substrate tyrosine phosphorylation and to initiate and sustain activation of mitogen-activated protein kinase. We conclude that the ability of ErbB4 to mediate signal transduction through EGF-like ligands is broader than previously assumed and can be profoundly altered by the concomitant expression of ErbB2.

Amphiregulin↗
PubMed1998

p53 point mutation enhanced by hepatic regeneration in aflatoxin B1-induced rat liver tumors and preneoplastic lesions.

Aflatoxin B1 (AFB1) is a well-known mutagen and carcinogen which induces human hepatocellular carcinoma (HCC). It has been found to be an important factor in inducing a high frequency of codon 249 mutation in the p53 gene. We characterized p53 mutations in specimens from preneoplastic lesions or tumors from the liver of rats induced by AFB1 with or without regeneration by partial hepatectomy treatment. PCR-SSCP and direct sequencing were used for screening and identification of p53 gene mutations in these samples. In rats treated with AFB1 with or without liver regeneration, 29% (5/17) of rats with hepatoma or neoplastic lesion had p53 mutation. No p53 mutations were found in the tumor samples from the rats without liver regeneration. However, in samples from the rats with liver regeneration, 38% (5/13) of the rats with hepatoma or neoplastic lesion were found to have p53 mutations. In one of these samples, we also observed a transversion mutation G --> T on codon 247, compared to codon 249 in humans. These findings suggest that the process of hepatocarcinogenesis induced by AFB1 does not necessarily involve p53 mutation, but mutation of the p53 gene can be enhanced by liver regeneration and that there is a possibility of a high mutability of the third base of codon 247, even though there is a small probability of detecting such a mutation in rats due to its silent mutation.

Aflatoxin B1↗
PubMed1998

A single amino acid substitution in the human and a bacterial hypoxanthine phosphoribosyltransferase modulates specificity for the binding of guanine.

Early studies involving purine salvage in Salmonella typhimurium resulted in the isolation and identification of a mutant strain possessing a genetically modified hypoxanthine phosphoribosyl-transferase (HPRT) with enhanced substrate specificity for guanine [Benson, C. E., and Gots, J. S. (1975) J. Bacteriol. 121, 77-82]. To explore the molecular basis for this altered substrate specificity in the mutant hpt gene product, degenerate oligonucleotide primers, designed according to the N- and C-termini of the HPRT of Escherichia coli, were used in polymerase chain reactions to amplify both the mutant and wild-type S. typhimurium hpt genes from genomic DNA. Analysis of the deduced amino acid sequences revealed that a single base mutation resulted in the encoding of a Thr in the mutant HPRT, instead of an Ile found in the wild-type enzyme, at a position analogous to position 192 (Leu-192) of the human HPRT. Comparison of kinetic data for purified recombinant mutant and wild-type HPRTs showed no difference in the overall catalytic efficiency (kcat/K(m)) with hypoxanthine as substrate, but with guanine, the mutant enzyme exhibited a more than 50-fold higher kcat/K(m) largely as a result of a decrease of nearly 2 orders of magnitude in K(m). Involvement in substrate binding of the cognate amino acid at position 192 in the human HPRT was investigated using site-directed mutagenesis. Mutation of Leu-192 to Thr did not significantly alter kcat/K(m) values for hypoxanthine and guanine compared to wild-type, and replacement of Leu-192 with Ile had no significant change in kinetics for either hypoxanthine or PRPP. However, this Ile substitution resulted in an over 15-fold decrease in the kcat/K(m) for guanine due to a greater than 15-fold increase in K(m). These results demonstrate that a single active site amino acid substitution in HPRTs can significantly alter the specificity for binding guanine.

Amino Acid Sequence↗
PubMed1998

Partial trisomy 8q and partial monosomy 15q associated with congenital hydrocephalus, diaphragmatic hernia, urinary tract anomalies, congenital heart defect and kyphoscoliosis.

We describe perinatal findings in a female fetus with partial trisomy 8q(8q24.1-->8qter) and partial monosomy 15q(15q26.1-->15qter) resulting from a paternal t(8;15) reciprocal translocation. Prenatal sonographic examination showed intra-uterine growth retardation, bilateral ventriculomegaly, cardiomegaly with arrhythmia, anhydramnios, and absent kidney and urinary bladder images. The pregnancy was terminated at 28 weeks of gestation. At birth, the infant manifested typical dysmorphic features of partial trisomy 8q. Necropsy further revealed hydrocephalus, congenital diaphragmatic hernia, ventricular septal defect, a horseshoe kidney with renal hypoplasia, and kyphoscoliosis. Our case shows that the coexistence of partial trisomy 8q24.1-->8qter and partial monosomy 15q26.1-->15qter are more detrimental than either defect alone and can result in a complex of major malformations. Prenatal ultrasound examination and cytogenetic assessment should be offered in subsequent pregnancies.

Abnormalities, Multiple↗
PubMed1998

Mutation analysis of Wilson disease in Taiwan and description of six new mutations.

Wilson disease is an autosomal recessive disorder of copper metabolism. Mutation screening in Wilson disease has led to the detection of at least 89 disease-specific mutations. Some mutations appear to be population specific, while others are common to many populations. In this study, 38 Taiwanese patients with Wilson disease were screened using single-strand conformation polymorphism analysis, followed by direct DNA sequencing. We found 12 different mutations, six of which were novel. All our detected mutations were found to be in eight exons. Four mutations in three loci (Arg778Gln, Arg778Leu, Gly943Asp, and Pro992Leu) accounted for about 58% of the mutant alleles we detected. Using an RNA transcriptional assay, we confirmed that both of our detected splice-site mutations resulted in exon skipping.

Alleles↗
PubMed1998

A prospective approach to correct for inter-image head rotation in fMRI.

Global head motion occurring between successive image acquisitions during a functional MRI time series can corrupt the signal of physiologic brain activation, potentially invalidating interpretation of the final activation map from that particular fMRI time series. By approximating the head as a rigid body, multiaxial global head motion can be decomposed into orthogonal linear and rotational components. This paper describes a method using orbital navigator echoes to provide prospective correction for both through-plane and in-plane inter-image head rotation in functional MRI. The dynamic detection and correction of rotation can be performed in <100 ms. Phantom experiments demonstrate accurate correction of rotational motion over a range of +/-0.36 degrees to +/-12 degrees. Imaging studies in volunteers document the feasibility of real-time prospective correction of rotational motion in vivo. Using a modified receiver operating characteristic method, motion-corrected functional MRI sensorimotor studies incorporating deliberate head rotations are shown to be superior to functional MRI time series acquired under similar conditions but without motion correction.

Artifacts↗
PubMed1998

Imaging of huge lingual thyroid gland with goitre.

We present the CT and MRI findings in a 75-year-old woman with a huge pathologically proven lingual thyroid which underwent goitrous degeneration. CT and MRI showed a midline, tongue-based, exophytic mass with areas of necrosis and heterogeneous contrast enhancement, as seen in large goitres in the normal thyroid gland.

Aged↗