Delayed onset of hand tremor related to cerebellar hemorrhage.
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Biomedical subjects
Publications and source records attributed to D C Chang.
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A G209A mutation in the alpha-synuclein gene was recently discovered in a large Italian kindred and three unrelated Greek kindreds with autosomal dominant Parkinson's disease (PD). Subsequently, another mutation in the gene (G88C) was also identified in a German family with autosomal PD. These results indicate that the alpha-synuclein gene may have an important role in the pathogenesis of PD. This study was designed to screen the existence of both mutations of the alpha-synuclein gene among 100 Chinese patients with PD, including 80 with sporadic and 20 with familial PD. Results showed that none of our patients, both sporadic and familial PD, had either of the two mutations of this gene. We therefore conclude that although of great interest, these two mutations are not relevant for the pathogenesis of PD in a Han Chinese population.
It has been suggested by many studies that Ca2+ signaling plays an important role in regulating key steps in cell division. In order to study the down stream components of calcium signaling, we have fused the gene of calmodulin (CaM) with that of green fluorescent protein (GFP) and expressed it in HeLa cells. The GFP-CaM protein was found to have similar biochemical properties as the wild-type CaM, and its distribution was also similar to that of the endogenous CaM. Using this GFP-tagged CaM as a probe, we have conducted a detailed examination of the spatial- and temporal-dependent redistribution of calmodulin in living mammalian cells during cell division. Our major findings are: (1) high density of CaM was found to distribute in two sub-cellular locations during mitosis; one fraction was concentrated in the spindle poles, while the other was concentrated in the sub-membrane region around the cell. (2) The sub-membrane fraction of CaM became aggregated at the equatorial region where the cleavage furrow was about to form. The timing of this localized aggregation of CaM was closely associated with the onset of cytokinesis. (3) Using a TA-CaM probe, we found that the sub-membrane fraction of CaM near the cleavage furrow was selectively activated during cell division. (4) When we injected a CaM-specific inhibitory peptide into early anaphase cells, cytokinesis was either blocked or severely delayed. These findings suggest that, in addition to Ca2+ ion, CaM may represent a second signal that can also play an active role in determining the positioning and timing of the cleavage furrow formation.
This 29-year-old man with cerebral palsy complicated by generalized dystonia was treated by simultaneous bilateral posteroventral pallidotomy. Postoperatively, there was slow, but steady, improvement in the patient's dystonia and disability. However, the improvement in abnormal movements was only prominent for cervical dystonia and oromandibular dyskinesia. The patient's Burke-Fahn-Marsden dystonia scores were 51 preoperatively and 37, 33.5 and 33.5, at 3, 6, and 12 months postoperatively, respectively, demonstrating a maximum improvement of 34%. These results suggest that pallidotomy can be an alternative therapy for those patients suffering from intractable generalized dystonia.
BACKGROUND: The association between deletion/insertion polymorphism of the angiotensin I-converting enzyme (ACE) gene and ischemic vascular diseases (IVDs) is still unclear. This study was designed to evaluate the role of ACE gene polymorphism in the pathogenesis of IVDs in a Chinese population living in Taiwan. METHODS: A case-control study was carried out to examine the association of the ACE gene genotype and the allele frequency in 400 IVD patients, including 214 patients with ischemic cerebrovascular disease (ICVD) and 186 patients with ischemic heart disease (IHD), compared with 200 control individuals. RESULTS: Although the patients with ICVD and IHD were found to have higher frequencies of the D/D genotype (22% and 43%) and the D allele (20% and 42%) than the controls (16% and 39%), the statistical differences were not significant, as shown by chi 2 analysis (p > 0.05). Upon further comparison of the frequencies of the D allele among the two sexes and different age subgroups, there was still no significant association. CONCLUSIONS: Deletion polymorphism of the ACE gene was not associated with IVD in a Chinese population in Taiwan. The unique or synergistic effect of other genes that might contribute to the pathogenesis of IVDs needs further investigation.
The adaptive contrast enhancement (ACE) algorithm, which uses contrast gains (CG's) to adjust the high-frequency components of images, is a well-known technique for medical image processing. Conventionally, the CG is either a constant or inversely proportional to the local standard deviation (ILSD). However, it is known that conventional approaches entail noise overenhancement and ringing artifacts. In this paper, we present a new ACE algorithm that eliminates these problems. First, a mathematical model for the LSD distribution is proposed by extending Hunt's image model. Then, the CG is formulated as a function of the LSD. The function, which is nonlinear, is determined by the transformation between the LSD histogram and a desired LSD distribution. Using our formulation, it can be shown that conventional ACE's use linear functions to compute the new CG's. It is the proposed nonlinear function that produces an adequate CG resulting in little noise overenhancement and fewer ringing artifacts. Finally, simulations using some X-ray images are provided to demonstrate the effectiveness of our new algorithm.
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BACKGROUND: The carbapenems, a class of beta-lactam antimicrobials with efficacy against both aerobic and anaerobic organisms, have demonstrated potential as monotherapeutic regimens in the treatment of serious intra-abdominal infections. Clinical trials have been conducted in the past decade to compare carbapenem monotherapy versus combinations of antibiotic therapy. We report here a meta-analysis of 10 such trials. DATA SOURCES: An 11-year Medline search (from 1985 through 1996) of the English-language literature identified clinical trials that compared the outcomes of carbapenem monotherapy, either imipenem/cilastatin or meropenem, versus another antibiotic regimen in intra-abdominal infections in human subjects. Ten randomized, prospective trials were found, with a total of 1,227 clinically evaluable patients. A meta-analysis of these clinical trials was performed to determine the difference in clinical outcomes between carbapenem monotherapy versus other antibiotic regimens. We found a difference in response rates of -1.6% (95% confidence interval [CI] -5.7% to 2.5%) and a response ratio of 0.99 (95% CI, 0.90 to 1.09), indicating no statistical significant difference. CONCLUSIONS: A meta-analysis of 10 clinical trials from 1985 through 1996 has revealed no statistical significant difference in clinical response between carbapenem monotherapy and combinations of antibiotic therapy in intra-abdominal infections. We noted, however, that the earlier studies reported more favorable response ratios for carbapenems than later publications. This may have been due to the selection of less effective comparators in earlier studies. We conclude that carbapenem monotherapy is as effective as combinations of antimicrobials for the treatment of intra-abdominal infections.
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OBJECTIVE: The aim of this study was to test the effectiveness of various attitude-behavior theories in explaining alcohol use among young adults. The theory of reasoned action (TRA), the theory of planned behavior and an extension of the TRA that incorporates past behavior were compared by the method of maximum-likelihood estimation, as implemented in LISREL for Windows 8.12. METHOD: Respondents consisted of 122 university students (82 female) who were questioned about their attitudes, subjective norms, perceived behavioral control, past behavior and intentions relating to drinking behavior. Students received course credit for their participation in the research. RESULTS: Overall, the results suggest that the extension of the theory of reasoned action which incorporates past behavior provides the best fit to the data. For these young adults, their intentions to drink alcohol were predicted by their past behavior as well as their perceptions of what important others think they should do (subjective norm). CONCLUSIONS: The main conclusions drawn from the research concern the importance of focusing on normative influences and past behavior in explaining young adult alcohol use. Issues regarding the relative merit of various alternative models and the need for greater clarity in the measure of attitudes are also discussed.
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Previous studies showed that localization of nucleophosmin/B23 (NPM) to nucleoli requires adequate cellular GTP levels (Finch et al., J Biol Chem 268, 5823-5827, 1993). In order to study whether hydrolysis of GTP plays a role in NPM localization, we introduced a nonhydrolyzable GTP analog into HeLa cells. Cells were first depleted of GTP with the IMP dehydrogenase inhibitor, mycophenolic acid (MA), to induce translocation of NPM from the nucleoli to the nucleoplasm. Non-hydrolyzable GTP analogs were then introduced into cells by electroporation. We found that introduction of the non-hydrolyzable analog, GTP gamma S, was effective in restoring NPM localization to nucleoli. Cells incubated in medium containing G-nucleotides without electroporation showed no effect. To reduce the possibility that cells use guanine from degraded nucleotide to supplement GTP pools via salvage pathways, experiments were also performed in the presence of (6-mercaptopurine) 6MP, a competitive inhibitor of the salvage enzyme, HGPRT (hypoxanthine guanine phosphoribosyl transferase), in addition to MA. Under these conditions, introduction of GTP gamma S still effectively restored the localization of NPM into nucleoli. This study demonstrates that electroporation can be used effectively to introduce nucleotides into cultured cells without excessive loss of viability. Our results also indicate that the GTP dependent localization of NPM to the nucleoli may not require GTP hydrolysis.
The use of metal-backed tibial plates in total knee replacement prostheses can result in the flow of ultra-high molecular weight polyethylene (UHMWPE) from the tibial insert into a cavity on the metal tray surface. A study of the relationship between the thickness of UHMWPE inserts and the amount of cold extrusion is reported here. An attempt was made to correlate the occurrence of cold extrusion with computer-aided analysis. UHMWPE samples of varying thickness, from 3 mm to 10 mm, were placed over cobalt-chrome (Co-Cr) discs. The Co-Cr discs had a 5 mm diameter hole placed centrally to simulate a tibial tray cavity. A cyclic load was applied at 20 Hz through a Co-Cr spherical indentor for a million cycles. The application of cyclic loading on UHMWPE samples resulted in cold-extrusion values comparable to those reported for retrieval analysis studies. Results after fatigue loading show that the samples do not suffer any gross surface damage. A shiny depression was visible at the load application site and the surface roughness value was decreased. The amount of cold extrusion increased with decreasing UHMWPE sample thickness. From the results, a minimum UHMWPE thickness of 12 mm is required if cold extrusion of UHMWPE is to be eliminated.
Cytokinesis, a key step in cell division, is known to be precisely regulated both in its timing and location. At present, the regulatory mechanism of cytokinesis is not well understood, although it has been suggested that calcium signaling may play an important role in this process. To test this notion, we introduced a sensitive fluorescent Ca2+ indicator into the zebrafish embryo and used confocal microscopy to measure the spatiotemporal variation of intracellular free Ca2+ concentration ([Ca2+]i) during cell cleavage. It was evident that a localized elevation of [Ca2+]i is closely associated with cytokinesis. First, we found that during cytokinesis, the level of free Ca2+ was elevated locally precisely at the cleavage site. Second, the rise of free Ca2+ was very rapid and occurred just preceding the initiation of furrow contraction. These observations strongly suggest that cytokinesis may be triggered by a calcium signal. In addition, we found that this cytokinesis-associated calcium signal arose mainly from internal stores of Ca2+ rather than from external free Ca2+; it could be blocked by the antagonist of inositol trisphosphate (InsP3) receptors. These findings suggest that the localized elevation of [Ca2+]i is caused by the release of free Ca2+ from the endoplasmic reticulum through the InsP3-regulated calcium channels.
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ISGF3 is a major protein factor which mediates the transcriptional activation of interferon-inducible genes. ISGF3 is composed of two subunits, ISGF3 gamma and ISGF3 alpha, which are stimulated by interferon-gamma (IFN-gamma) and interferon-alpha (IFN-alpha), respectively. In this paper, the effect of pretreatment of IFN-gamma on the response of K562 cells to IFN-alpha, termed "gamma-priming," is examined. Using techniques of gene transfection and mobility shift assay, we studied the gamma-priming effects on the kinetics of appearance and disappearance of (i) the protein product of a luciferase reporter gene driven by an IFN-inducible promoter and (ii) the binding of ISGF3 to the interferon-stimulated response element. We found that exposure of cells to IFN-gamma prior to IFN-alpha greatly increased both the levels and the rate of ISGF3 binding activity during the early phase of IFN-alpha treatment and caused the amount of ISGF3 bound to the interferon-stimulated response element to decrease more rapidly with time during the later phase. Such effects were reflected also on the kinetics of expression of the interferon-inducible luciferase gene induced by IFN-alpha. In order to understand the basis of these gamma-priming effects, we use an in vitro reconstitution method to examine the kinetics of the subcomponents of ISGF3 in response to different IFN treatments in K562 cells. It was found that gamma-priming not only increased the levels of ISGF3 gamma, but it also stimulated both the rates of rise and fall of the activated alpha-component of ISGF3. A molecular model is proposed to explain these findings.
This report describes the structure of soluble human stem cell factor isolated from the conditioned medium of Chinese hamster ovary (CHO) cells transfected with stem cell factor (SCF) cDNA, which encodes a leader sequence plus 248 additional amino acids. The 248 amino acids include a hydrophobic transmembrane region at positions 190-212. The isolated material is glycosylated and three bands (apparent M(r) 28,000, M(r) 35,000, and M(r) 40,000) are evident by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. After complete deglycosylation, the molecular weight by SDS-polyacrylamide gel electrophoresis is 18,000-19,000. Structural analyses of the intact SCF, the deglycosylated SCF, and a deglycosylated C-terminal peptide were performed by laser desorption, fast atom bombardment, or electrospray mass spectrometry. Pulse-labeling of cells with 35S-labeled Met and Cys resulted in cell-associated glycosylated SCF of M(r) 33,000-45,000 which was converted to M(r) 33,000 by in vitro treatment with glycosidases. During a chase with unlabeled Met and Cys, labeled SCF of M(r) 28,000, M(r) 35,000, and M(r) 40,000 appeared in the medium; it was converted to M(r) 18,000-19,000 by glycosidase treatment. SCF at the surface of the transfected CHO cells could be demonstrated by immunofluorescence. The data obtained indicate that the recombinant human stem cell factor, as isolated, represents proteolytically processed forms containing amino acids 1-165, derived from the initially synthesized membrane-bound form of 248 amino acids. Further characterization indicated that the M(r) 28,000 form is glycosylated at Asn120, the M(r) 35,000 form at Asn120 and Asn65, and the M(r) 40,000 form at Asn120, Asn93, and Asn65. Each form also contains O-linked carbohydrate. The N-linked glycosylation, particularly that at Asn93 and at Asn65, adversely affects in vitro biological activity and receptor binding.