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Biomedical subjects

J H Cha

Publications and source records attributed to J H Cha.

At least 19 recordsLinked to original sources

High frequency broadband PZT thick film ultrasonic transducers for medical imaging applications.

A modified sol-gel method is used to prepare PZT thick film on Pt-coated silicon substrate. A new method of vacuum filling sol-gel precursor solution is introduced to improve film quality. The effects of the filling on PZT thick film structure and ferroelectric properties are discussed. The fabrication of a high frequency transducer with the PZT film as the actuating layer is described. The performance of the transducer is measured and results show that the transducer backed by E-Solder without a matching layer has a center frequency of 103 MHz and a bandwidth of 70%. Beam profile measurements show that the transducer has an axial resolution of 9.2 microm and a lateral resolution of 33 microm.

Electromagnetic Phenomena↗

Synthesis and In vitro binding affinities of 1-azabicyclic compounds as muscarinic ligands.

Two series of compounds, 2 and 3, were synthesized and their binding affinities were evaluated for the human recombinant muscarinic M(1) receptor subtype expressed in CHO cells. Comparing their binding affinities for the NMS binding sites and the Oxo-M binding sites, they were assumed as agonists. In particular, compound 2e was a good ligand for the agonist binding sites with an IC(50) of 23 nM, which represents over 1585 times stronger binding than for the antagonist binding sites.

Animals↗

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗

Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor protein.

Alzheimer's disease transgenic mice overexpressing human amyloid precursor protein (hAPP) with the Swedish double mutation (hAPP(Sw)) develop age-related amyloid deposition and behavioral and electrophysiologic changes by an unknown mechanism. Analysis of glutamatergic receptor subtypes in 4- and 15-month-old heterozygous hAPP(Sw) transgenic mice revealed a selective increase in AMPA receptor binding in the hippocampus of 15-month-old transgenic mice, which have established cortical and hippocampal amyloid deposits. There were no significant alterations of GluR1, GluR2, and GluR4 protein expression by semiquantitative confocal analysis or GluR1 mRNA by in situ hybridization. There was no significant alteration in NMDA, in group I and II metabotropic glutamate and in muscarinic receptor binding, or in striatal dopamine and adenosine receptor binding in 15-month-old mice. These data suggest that mutant APP overexpression or age-related amyloid deposition produce a subtle specific alteration in hippocampal glutamate receptors with aging.

Amyloid beta-Protein Precursor↗

Expression of osteopontin mRNA in developing rat brainstem and cerebellum.

This study was undertaken to investigate the developmental expression of osteopontin (OPN) in the rat brainstem and cerebellum by Northern blotting and in situ hybridization. The expression of OPN was noted in the mesencephalic Vth nucleus initially at embryonic day 16 (E16). At E20, the labeling extended into other brainstem nuclei including the cochlear, vestibular, facial motor, and hypoglossal nuclei. During the first week of postnatal life, the OPN signal in the brainstem increased markedly, and by P14, OPN expression was found in functionally diverse areas including motor-related areas, sensory relay nuclei, and the reticular formation. The adult labeling pattern was established in central neurons at this time. These results corresponded well with those from Northern blot analysis. On the basis of morphological and distribution criteria, the OPN signal in several nuclei appeared to be contained exclusively within neuronal soma. OPN expression in neurons occurred during the period of neuronal differentiation and increased with maturation. Our results therefore suggest that OPN contributes to developmental processes, including the differentiation and maturation of specific neuronal populations, in the rat brain.

Animals↗

Treatment of vitiligo with suction epidermal grafting by the use of an ultrapulse CO2 laser with a computerized pattern generator.

BACKGROUND: Laser ablation is used to remove the recipient epidermis in the suction epidermal grafting in vitiligo surgery. OBJECTIVE: To evaluate the effectiveness and safety of a suction epidermal grafting method after the removal of the epidermis by the use of the Ultrapulse CO2 laser with a computerized pattern generator. METHODS: Eleven patients with 34 lesions of refractory stable vitiligo were studied. RESULTS: Of the 34 lesion sites, excellent repigmentation was seen in 30 and the other 4 had good repigmentation. No complications occurred. CONCLUSION: The Ultrapulse CO2 laser is particularly well suited for deepithelialization in vitiligo surgery.

Adolescent↗

Six cases of confluent and reticulated papillomatosis alleviated by various antibiotics.

Confluent and reticulated papillomatosis (CRP) is a relatively rare disorder manifested by persistent papules that are confluent in the center and reticulated at the periphery with a characteristic distribution. Recently, many cases of CRP treated with minocycline have been reported, and their effect seems to be derived from their antibiotic properties. We report 6 cases of CRP alleviated by various antibiotics. The patient described in case 1 is a 16-year-old girl whose disease was alleviated by oral minocycline, 100 mg daily for 8 weeks. Cases 2 and 3 describe an 18-year-old woman and a 17-year-old male adolescent whose disease was reduced by oral fusidic acid, 1000 mg daily for 4 weeks. Case 4 describes a 14-year-old girl who received oral clarithromycin, 500 mg daily for 5 weeks. Case 5 describes a 22-year-old woman whose disease was reduced by oral erythromycin, 1000 mg daily for 6 weeks. Case 5 reports a 24-year-old man who received oral azithromycin, 500 mg daily 3 times per week for 3 weeks. Complete clearing after treatment with antibiotics raises the possibility that CRP is triggered by a bacterial infection and that antibiotics are the treatment of choice for CRP.

Adolescent↗

Remotivation therapy and Huntington's disease.

Huntington's disease (HD) is a genetic, autosomal dominant, neurodegenerative disorder for which there is no known cure. Because remotivation therapy (RmT) has been effective in other neurological conditions and because of the lack of current efficacious treatments for HD, RmT may be a beneficial therapy for persons suffering from the disease. By cultivating a more fertile environment, RmT leads to increased self-awareness, self-esteem, and an improved quality of life, even in late-stage HD. Two recent studies using animal models suggest that exposure of transgenic HD mice to a stimulating, enriched environment helped to prevent the loss of cerebral volume and delay the onset of motor disorders. Six case studies are presented that demonstrate improved physical, mental, and social functioning in persons with HD when a more stimulating environment is provided.

Adaptation, Psychological↗

Ultrasonographic evaluation of the gallbladder: comparison of fundamental, tissue harmonic, and pulse inversion harmonic imaging.

The purpose of our study was to compare pulse inversion harmonic imaging, tissue harmonic imaging, and fundamental imaging in the evaluation of normal and diseased gallbladder. Gallbladders in 170 patients were examined with fundamental imaging, tissue harmonic imaging, and pulse inversion harmonic imaging using a 2- to 5-MHz curved array transducer. Images were divided into normal and abnormal groups. The sharpness of the wall and degree of internal artifact were evaluated in normal groups, and lesion conspicuity and internal artifact were evaluated in abnormal groups. In images of both normal and abnormal gallbladder, significant differences were demonstrated among the 3 imaging methods (P < .001), and pulse inversion harmonic imaging provided the best image quality and the least artifact. Tissue harmonic imaging was the next best, providing better image quality and less artifact than fundamental imaging. In conclusion, pulse inversion harmonic imaging provided the best image quality and the least artifact among the 3 ultrasonographic methods in the evaluation of both normal and abnormal gallbladder.

Aged↗

Up-regulated CNTF plays a protective role for retrograde degeneration in the axotomized rat retina.

Using reverse transcription-polymerase chain reaction and in situ hybridization, we investigated the expression and cellular localization of ciliary neurotrophic factor receptor alpha (CNTFRalpha) in the rat retina following optic nerve transection (ONT). Following ONT, a signal for CNTFRalpha mRNA appeared in a layer-specific and time-dependent manner. In the ganglion cell layer, the signal showed a peak value 1 day after ONT, and then gradually decreased. In the inner nuclear layer the signal reached a peak value at 14 days of about 500% of control level, but then decreased at 4 weeks. Our findings suggest that CNTF might play a protective role for the retrograde degeneration of retinal cells induced by ganglion cell death in the rat retina following ONT.

Animals↗

Molecular characterization of key diphtheria toxin:receptor interactions.

The major amino acids necessary for diphtheria toxin (DT) binding to its receptor have been identified previously. Studies by W. H. Shen et al. (J. Biol. Chem. 269, 29077-29084, 1994) and by J. H. Cha et al. (Mol. Microbiol. 29 (5), 1275-1284, 1998) suggested that the positively charged nature of the single amino acid residue, (516)Lys of DT, is crucial for binding to the DT receptor, whereas the negatively charged (141)Glu of the DT receptor is the most important residue for toxin binding. Here, we hypothesize that key interactions occur between these two oppositely charged amino acid residues. Reciprocal substitution of the residues at these positions between the toxin and the receptor was performed, which resulted in a partial reconstitution of the toxin:receptor interaction. This study provides the first biological data that characterizes the specific interaction of these two key residues with each other and also the additional interactions between other positively charged residues of DT and (141)Glu of the DT receptor.

Animals↗

Decreased expression of striatal signaling genes in a mouse model of Huntington's disease.

To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile approximately 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.

Adenylyl Cyclases↗

Cell surface monkey CD9 antigen is a coreceptor that increases diphtheria toxin sensitivity and diphtheria toxin receptor affinity.

Monkey (Mk) CD9 antigen has been shown previously to increase the diphtheria toxin (DT) sensitivity of cells when co-expressed with Mk proHB-EGF (DT receptor). We have elucidated here the mechanism whereby Mk CD9 influences Mk proHB-EGF and present evidence that Mk CD9 is a coreceptor for DT. We observed that Mk CD9 not only increased the DT sensitivity but also increased the DT receptor affinity of cells. Furthermore, the higher the Mk CD9/Mk proHB-EGF ratio, the higher the affinity. In contrast, mouse (Ms) CD9 did not increase the toxin sensitivity or receptor affinity of cells when co-expressed with Mk proHB-EGF. Using Mk/Ms chimeric CD9 molecules, we determined that the second extracellular domain of Mk CD9 is responsible for both increased sensitivity and receptor affinity. This domain of Mk CD9 also interacts with Mk proHB-EGF in a yeast two-hybrid system. Our findings thus suggest that Mk CD9 has a direct physical interaction with Mk proHB-EGF to form a DT receptor complex and that this contact may change the conformation of the receptor to increase DT binding affinity and consequently increase toxin sensitivity. We thus propose that Mk CD9 is a coreceptor for DT.

Amino Acid Sequence↗

Ganglion cells of the rat retina show osteopontin-like immunoreactivity.

Osteopontin (OPN) is a negatively charged, highly acidic glycosylated phosphoprotein that contains an GRGDS amino acid sequence, characteristic of proteins that bind to integrin receptors, thereby playing crucial roles in a number of physiological processes. This study was conducted to examine the expression of OPN in the rat retina by Northern blot analysis, Western blot analysis and immunocytochemistry. The expression of OPN was identified in the retina and OPN-like immunoreactivity was present in a number of ganglion cells. Thus, OPN appears to be important in the retinal homeostasis.

Animals↗

Transcriptional dysregulation in Huntington's disease.

Although the gene responsible for Huntington's disease was discovered in 1993, the pathogenic mechanisms by which mutant huntingtin causes neuronal dysfunction and death remain unclear. However, increasing evidence suggests that mutant huntingtin disrupts the normal transcriptional program of susceptible neurons. Thus, transcriptional dysregulation might be an important pathogenic mechanism in Huntington's disease.

Humans↗

Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease.

Huntington disease is an autosomal dominant neurodegenerative disease with no effective treatment. Minocycline is a tetracycline derivative with proven safety. After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction. As caspase-1 and nitric oxide seem to play a role in Huntington disease, we evaluated the therapeutic efficacy of minocycline in the R6/2 mouse model of Huntington disease. We report that minocycline delays disease progression, inhibits caspase-1 and caspase-3 mRNA upregulation, and decreases inducible nitric oxide synthetase activity. In addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3 inhibition. This is the first demonstration of caspase-1 and caspase-3 transcriptional regulation in a Huntington disease model.

Animals↗

A case of classic Kaposi's sarcoma with multiple organ involvement.

Kaposi's sarcoma is a systemic, multifocal, angiomatous tumor which can be classified into four clinical variants. Among them, classic Kaposi's sarcoma is rare in Oriental people, and the involvement of internal organs in this variant is reported to be very rare. We present a case of classic Kaposi's sarcoma in a 67-year-old Korean male, who had multiple organ involvement in the skin, lymph node, and stomach. Lesions of Kaposi's sarcoma cleared after treatment with etoposide, but the skin lesions recurred after a three-month symptom-free period. He was treated with doxorubicin, bleomycin, and vincristine, and all the skin lesions were cleared.

Aged↗