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Biomedical subjects

C C Lee

Publications and source records attributed to C C Lee.

At least 289 records · Page 16Linked to original sources

Panencephalitic Creutzfeldt-Jakob disease. Unusual presentation of magnetic resonance imaging and proton magnetic resonance spectroscopy.

We present serial magnetic resonance imaging (MRI) scans on a biopsy-verified case of Creutzfeldt-Jakob disease (CJD). The initial MRI scan demonstrated increased T2 signal-intensity within the basal ganglia and thalami. Subsequent MRI scans demonstrated a thin cortex, increased T2 signals diffusely within the white matter including U-fibers, and hypointense T2 signals within the basal ganglia, and thalami. Proton magnetic resonance spectroscopy (1H-MRS) study showed an absence of creatine, choline and N-acetylaspartate signals. By these characteristic findings, serial MRI and MRS studies may be helpful in differentiating CJD from other dementing illnesses.

Biopsy↗

The effects of nerve growth factor and ganglioside GM1 on the anti-proliferative activity of cocaine in PC12 cells.

The anti-proliferative activity of cocaine was determined in PC12 phenochromocytoma cells. The effects of nerve growth factor (NGF) and ganglioside GM1 (GM1) on the toxicity of this stimulant of abuse was examined over a period of 72 h. Cocaine (40 microM-320 microM) exhibited a dose-dependent inhibition of cellular proliferation as determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction. While NGF (100 ng/ml) and GM1 (100 microM) alone partially reversed the cocaine-induced inhibition of proliferation, the combination of NGF and GM1 afforded additional protection that was greater than that of either agent individually.

Animals↗

A comparative transcription map of the murine bare patches (Bpa) and striated (Str) critical regions and human Xq28.

The X-linked developmental mouse mutations bare patches (Bpa) and striated (Str) may be homologous to human X-linked dominant chondrodysplasia punctata (CDPX2) and incontinentia pigmenti (IP2), respectively, based on their genetic mapping and clinical phenotypes. Bpa and Str have been localized to an overlapping critical region of 600 kb that demonstrates conserved gene order with loci in human Xq28 between DXS1104 and DXS52. As part of efforts to isolate the genes involved in these disorders, we have begun to develop a comparative transcription map spanning this region in both species. Using techniques of cross-species conservation and hybridization, exon trapping, and cDNA selection we have identified four known genes or members of gene families--caltractin, a member of the gamma-aminobutyric acid (GABAA) receptor gene family, a member of the melanoma antigen gene (MAGE) family, and several members of the murine-specific, X-linked lymphocyte regulated gene (Xlr3) family. Trapped exons and, in some cases, longer cDNAs have been isolated for potentially 7-9 additional genes. One cDNA demonstrates highly significant homology with members of the Krüppel family of zinc finger transcription factors. A second novel cDNA demonstrates homology at the 3' end of the predicted amino acid sequence to a LIM domain consensus. Gene order appears conserved among those cDNAs determined to be present in both human and mouse. Three of the murine transcripts appear to be present in multiple copies within the Bpa/Str critical region and could be associated with a predisposition to genomic rearrangements. Reverse transcriptase PCR (RT-PCR) and Northern analysis demonstrate that several of the transcripts are expressed in mid-gestation murine embryos and neonatal skin, making them candidates for the Bpa and Str mutations and their respective homologous human disorders.

Amino Acid Sequence↗

A robust sequential test for text-independent speaker verification.

A robust speaker verification algorithm based on sequential hypothesis testing is presented. In speaker verification, the system performance is severely degraded by deviations from the nominal statistical speaker models caused by insufficient training data, varying microphone and transmission line characteristics, and different levels and types of background noise. Historically, this problem has been addressed by using an empirical method to determine an adequate decision threshold for a desired operating point. The robust detection algorithm presented here is based on a minimax criterion, such that the worst-case performance over a class of distributions is minimized. The sequential test provides further robustness by using additional data if a decision cannot be reached with the desired level of confidence. The sequential detector has been implemented and tested on a realistic database collected specifically for this purpose, and the performance has been shown to be comparable to or better than that of the corresponding heuristic detectors previously described in the literature.

Algorithms↗

The Drosophila P-element KP repressor protein dimerizes and interacts with multiple sites on P-element DNA.

Drosophila P elements are mobile DNA elements that encode an 87-kDa transposase enzyme and transpositional repressor proteins. One of these repressor proteins is the 207-amino-acid KP protein which is encoded by a naturally occurring P element with an internal deletion. To study the molecular mechanisms by which KP represses transposition, the protein was expressed, purified, and characterized. We show that the KP protein binds to multiple sites on the ends of P-element DNA, unlike the full-length transposase protein. These sites include the high-affinity transposase binding site, an 11-bp transpositional enhancer, and, at the highest concentrations tested, the terminal 31-hp inverted repeats. The DNA binding domain was localized to the N-terminal 98 amino acids and contains a CCHC sequence, a potential metal binding motif. We also demonstrate that the KP repressor protein can dimerize and contains two protein-protein interaction regions and that this dimerization is essential for high-affinity DNA binding.

Amino Acid Sequence↗

Prevalence of dermatoses and skin sensitisation associated with use of pesticides in fruit farmers of southern Taiwan.

OBJECTIVES: Agricultural workers are known to have occupational skin diseases. The prevalence and pattern of skin diseases are unknown in Taiwanese fruit farmers. The objective of this study is to determine the work exposure, prevalence of skin diseases, and sensitivity to common skin allergens and agricultural chemicals in fruit farmers of southern Taiwan. METHODS: 122 fruit farmers who regularly prepared and sprayed pesticides and a group of 63 printing press workers with no known exposure to pesticides were examined and patch tested with common skin allergens and agricultural chemicals. The farmers were also interviewed for their work habits, use of protective clothing, and exposure to pesticides. RESULTS: Most farmers reported regular use of hat, boots, and mask, but not gloves, raincoat, and goggles. This resulted in frequent skin contact with pesticides especially on the hands and face. About 30% of farmers had hand dermatitis, and more than two thirds had pigmentation and thickening on the hands. Fungal infection of the skin was noted in a quarter of subjects. By patch test, farmers and the printing press workers had a similar rate of sensitivity to common skin allergens. 40% of farmers were sensitive to agricultural chemical allergens, which was about twofold higher than that of the comparison group. Farmers were most frequently sensitive to Captofol, Folpet, and Captan which were associated with dermatitis on the volar aspects of the hands. CONCLUSIONS: Fruit farmers in southern Taiwan had a high prevalence of skin diseases related to use of pesticides, and appropriate protective measures and work practices should be taken to prevent such problems.

Adolescent↗

Pericerebral fluid collection: differentiation of enlarged subarachnoid spaces from subdural collections with color Doppler US.

PURPOSE: To determine if the cerebral cortical vain sign seen on magnetic resonance (MR) images can be used with color Doppler ultrasound (US) to differentiate enlarged subarachnoid space from subdural collection. MATERIALS AND METHODS: Eighteen infants with pericerebral fluid collection were prospectively examined with color Doppler US and MR imaging. Patients were classified into two groups: group A, with positive cortical vein sign (visualization of color-coded cortical veins that cross fluid collections at cerebral convexities); and group B, without the sign. RESULTS: Positive cortical vein sign was seen at US in 12 patients (group A): nine with benign enlargement of subarachnoid spaces, two with brain atrophy, and one with meningococcal meningitis. The veins were displaced and embedded within the echogenic pia-arachnoid that surrounds the brain or were trapped in the subarachnoid spaces between the neo-membrane and cortical surface (group B, negative cortical vein sign) in four patients with meningitis, two victims of child abuse, and one patient with leukemia. Findings from subsequent MR imaging confirmed the color Doppler US findings. CONCLUSION: Color Doppler US depiction of the cortical vain sign appears to be as effective as MR imaging in differentiating enlargement of the subarachnoid fluid space from subdural effusion.

Brain↗

Cytogenetic evaluation of cystic hygroma associated with hydrops fetalis, oligohydramnios or intrauterine fetal death: the roles of amniocentesis, postmortem chorionic villus sampling and cystic hygroma paracentesis.

BACKGROUND: Pregnancies complicated by fetal cystic hygroma in the second and third trimesters are often associated with hydrops fetalis, oligohydramnios or intrauterine fetal death which may make genetic assessment more difficult. We investigated the roles of amniocentesis, postmortem chorionic villus sampling and cystic hygroma paracentesis in cytogenetic evaluation of cystic hygroma under such circumstances. METHODS: Thirty-five fetuses of cystic hygroma associated with hydrops fetalis, oligohydrammos, or intrauterine fetal death were studied. All fetuses were delivered at Mackay Memorial Hospital, Taipei, Taiwan between January, 1987 and July, 1995. Data collected included maternal age, prenatal sonograms, gestational age at diagnosis, fetal karyotypes and diagnostic procedures. RESULTS: Of 35 fetuses, all had hydrops fetalis, 19 had suffered IUFD at the time of diagnosis, and 10 had severe oligohydramnios. Cytogenetic studies were performed via amniocentesis, postmortem chorionic villus sampling, or cystic hygroma paracentesis. Successful karyotyping was achieved in 32 fetuses and the karyotype of 45,X was found in 24 fetuses. In cases with IUFD, successful karyotyping rates on cells from amniotic fluid, chorionic villi and cystic hygroma fluid were 88.9% (8 of 9), 69.2% (9 of 13) and 20% (1 of 5), respectively, whereas, in cases with living hydropic fetuses, successful karyotyping was achieved in 12 of 12 amniotic fluid and 5 of 5 cystic hygroma fluid samples. CONCLUSIONS: Amniocentesis is a better method for cytogenetic evaluation of fetal cystic hygroma associated with intrauterine fetal death than postmortem chorionic villus sampling and cystic hygroma paracentesis. However, in the case with a living hydropic fetus and oligohydramnios, cystic hygroma paracentesis appears to be a practical alternative for cytogenetic assessment.

Adult↗

Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus.

We examined the effects of leptin, the product of the obese gene, on synaptic transmission in the arcuate nucleus in rat hypothalamic slices. Both leptin and neuropeptide Y (NPY) reduced the evoked glutamatergic excitatory postsynaptic current in the arcuate nucleus. NPY also depressed the GABAergic inhibitory postsynaptic current, although leptin had no effect. Leptin also decreased the input resistance of arcuate neurons, and this was accompanied by the activation of an outward current at depolarized potentials. Leptin modulated Ca2+ signals in acutely isolated arcuate neurons. In some cells, the intracellular calcium concentration rise produced by 50 mM K+ was decreased, whereas in others it was increased. However, leptin produced no effects on synaptic transmission and little or no effect on Ca2+ signaling in the hypothalamus of Zucker fatty rats that contain mutated leptin receptors. On the other hand, NPY exhibited synaptic modulatory effects in Zucker lean and fatty rats. These data suggest that leptin can produce rapid synaptic modulatory effects in the arcuate nucleus, which may contribute to its effects on food intake.

Animals↗

Mesencephalic cavernous hemangioma.

A 49-year-old female had experienced headaches and nausea for 2 months. Neurologic examinations showed mild blurring of the optic disc and limitation of ocular movement. Magnetic resonance imaging (MRI) studies disclosed a mass in the central and right paramedian mesencephalon with rostral extension to the third ventricle and the right side of the thalamus. This tumor had a peripheral low signal ring and a heterogeneous central signal on T1 weighted images. The findings were thought to be consistent with a cavernous hemangioma. The clear anatomic boundary of the lesion was defined by MRI enabling removal of the mesencephalic cavernoma. The patient headache remained well with no neurologic symptoms in the 3 years following the operation.

Brain Neoplasms↗

Use of functional magnetic resonance imaging.

It has been the goal of this article to provide the reader with a brief background of fMRI, a basic understanding of the techniques of fMRI, and, more importantly, the potential for clinical and experimental studies using fMRI. In contrast to the limited number of installed PET and MEG units, the large installed base of MR imaging scanners (over 1000 installed at least at 1.5 T in the United States) makes fMRI potentially widely available. Initial studies (both clinical and experimental) have been validated and are reproducible in mapping the sensorimotor and visual cortices. The areas of language lateralization and memory are still preliminary at best. As methods to reduce the effects of head motion (due to both bulk head motion and physiologically induced motion) arise, the reliability of fMRI should improve, allowing for more definitive identification of task activation.

Brain Diseases↗

Foodborne diseases.

Foodborne diseases continue to cause significant morbidity and mortality both in developing and developed countries. Its spectrum has vastly expanded in recent years with the recognition of new foodborne pathogens and clinical syndromes. The increase in international travel and demand for exotic and raw food underscore the importance of traveller's diarrhoea. The emergence of day care centres and residential institutions predispose to an environment that enhances the transmission of foodborne pathogens. Last but not least, our greying population, the AIDS pandemic and increasing use of immunosuppressive chemotherapy have produced a special population that is easily susceptible to the microbial contamination of food. Diseases in these individuals are usually more chronic, severe or life-threatening. This article seeks to address the above issues as well as to present a practical approach to the diagnosis and management of foodborne diseases.

Diarrhea↗

X-linked recessive myotubular myopathy proven by muscle biopsy.

We report a baby boy, the third child of a nonconsanguineous couple, with congenital myotubular myopathy. At birth, he had generalized hypotonia and respiratory distress. On physical examination, an elongated apathetic face, high-arched palate, bilateral ptosis, funnel chest, frog-leg posture, little spontaneous movement of the limbs and areflexia were observed. A chest x-ray revealed thin ribs and clavicles. The infant died 54 days after birth despite intensive management. The mother, a healthy 32-year-old female, displayed myotubes on muscle biopsy which suggested an X-linked recessive inheritance pattern for myotubular myopathy. This report illustrates the importance of taking a detailed family history as well as a muscle biopsy in the diagnosis of X-linked recessive myotubular myopathy.

Biopsy↗

The insulin receptor substrate-1-related 4PS substrate but not the interleukin-2R gamma chain is involved in interleukin-13-mediated signal transduction.

Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3-dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin-like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL-13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma), resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS.

Adaptor Proteins, Signal Transducing↗

A human homologue of the Drosophila polarity gene frizzled has been identified and mapped to 17q21.1.

The frizzled (fz) locus in Drosophila is required for the transmission of polarity signals across the plasma membrane in epidermal cells, as well as to their neighboring cells in the developing wing. The identification of a tissue polarity gene from the fz locus in Drosophila melanogaster has been reported. The fz gene encodes a protein (Fz) with seven putative transmembrane domains, which was suggested to function as a G-protein-coupled receptor. Here we report the identification of a human homologue for the fz gene (FZD2). The FZD2 gene was isolated from a human ovarian cDNA library and mapped to 17q21.1 by fluorescent in situ hybridization (FISH) with a corresponding cosmid. The full-length cDNA of human FZD2 encodes a protein (FZD-2) of 565 amino acids that shares 56% sequence identity with Drosophila Fz. The expression of the FZD2 gene seems to be developmentally regulated, with high levels of expression in fetal kidney and lung and in adult colon and ovary. The structure of FZD-2 suggests that it has a role in transmembrane signal transmission, although its precise physiological function and associated pathways are yet to be determined.

Animals↗

Alternatively spliced juxtamembrane domain of a tyrosine kinase receptor is a multifunctional regulatory site. Deletion alters cellular tyrosine phosphorylation pattern and facilitates binding of phosphatidylinositol-3-OH kinase to the hepatocyte growth factor receptor.

The hepatocyte growth factor (HGF) receptor is a tyrosine kinase receptor that mediates signal transduction upon ligand stimulation. This receptor is present in mouse tissues as two major isoforms differing by a 47-amino acid segment in the juxtamembrane domain, an alternatively spliced cytoplasmic region adjacent to the transmembrane domain of the receptor. We report here that the juxtamembrane domain of the receptor is involved in the regulation of downstream signal transduction. The two receptor isoforms were transiently expressed in COS-7 cells. Both exogenous receptors underwent autophosphorylation and subsequently stimulated a set of protein tyrosine phosphorylations that were not present in control cells. Comparisons of phosphotyrosine profiles of transfected cell lysates induced by receptor isoforms demonstrated that at least three phosphorylated proteins of approximately 62, approximately 35, and approximately 30 kDa were differentially induced by the receptor isoforms, suggesting that the juxtamembrane domain of a kinase receptor can play a role in selective signal transduction. Furthermore, the p85 subunit of phosphatidylinositol-3-OH kinase (PI3 kinase) co-precipitated with the small isoform of the HGF receptor, and this association was dramatically inhibited by treatment with 12-O-tetradecanoylphorbol-13-acetate. Since removal of the juxtamembrane domain facilitates the binding of p85 to the receptor, it is likely that the juxtamembrane region plays a role in negative regulation of the binding of PI3 kinase to the HGF receptor. Our study establishes novel molecular sequelae of alternative splicing of an intracellular domain of the HGF receptor.

Alternative Splicing↗

Multiple myeloma clones are derived from a cell late in B lymphoid development.

We have previously demonstrated that the immunoglobulin (Ig) heavy chain variable region (VH) sequences expressed by the malignant clone in multiple myeloma (MM) contain a high degree of somatic mutation without clonal diversity. This sequence can be used to identify all members of the malignant clone in this B cell malignancy. We sequenced the variable regions expressed by patients with MM and generated primers from the complementarity determining region (CDR) sequences specific for each patient's tumor. Using these primers, we performed PCR amplification on highly purified subpopulations of cells separated by expression of CD10, CD34 and CD38. The results of these experiments demonstrate: 1) there is a small fraction of CD10-expressing tumor cells in MM patients, 2) CD34-bearing malignant cells do not exist in MM, and 3) although the vast amount of tumor is in the CD38-expressing cells, a small amount of tumor is in the CD38-negative population. We also used these primers to determine whether pre-class switch (i.e., Cmu-expressing lymphocytes) clonal cells exist in these patients. After PCR amplification with CDR1 and Cmu primers, colony hybridization was performed using both framework 3 (FR3) and CDR3 probes. Out of > 200 FR3-hybridizing colonies, < or = 5 colonies also hybridized with the CDR3 probe. Colonies which hybridized with both these probes were sequenced, and none of these sequences matched even closely the CDR3 expressed by the malignant clone. These results make the existence of a pre-class switch malignant cell unlikely in MM. Overall, these results suggest that the malignant clone in MM derives from a cell late in B lymphocyte development.

ADP-ribosyl Cyclase↗