Biomedical subjects
G Choi
Publications and source records attributed to G Choi.
Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection.
Severe infection is associated with profound alterations in the systemic haemostatic balance, with activation of coagulation and suppressed fibrinolysis. Within the alveolar compartment, similar disturbances have been described during pulmonary inflammation. The current authors investigated whether local haemostasis was influenced during ventilator-associated pneumonia (VAP). In five patients with unilateral VAP, bronchoalveolar lavage fluid (BALF) was obtained from both the infected site (as identified on chest radiograph) and the contralateral noninfected lung (with no clinical or radiographic abnormalities). Markers for coagulation and fibrinolysis were compared between infected and noninfected lungs. A total of 10 healthy volunteers and 10 mechanically ventilated patients without pneumonia served as controls. Strong activation of coagulation (high levels of thrombin-antithrombin complexes, soluble tissue factor and factor VIIa) was detected in BALF from infected lungs, compared with that from noninfected lungs and controls. Furthermore, in infected lungs, fibrinolysis was depressed, with high levels of plasminogen activator inhibitor type 1. In conclusion, ventilator-associated pneumonia is characterised by a hypercoagulant state at the site of infection.
The cytoplasmic helix of cannabinoid receptor CB2, a conformational study by circular dichroism and (1)H NMR spectroscopy in aqueous and membrane-like environments.
The cytoplasmic helix domain (fourth cytoplasmic loop, helix 8) of numerous G protein-coupled receptors (GPCRs) such as rhodopsin and the beta-adrenergic receptor exhibit unique structural and functional characteristics. Computer models also predict this structure for the cannabinoid CB2 receptor, another member of the GPCR superfamily. In our study, a peptide corresponding to helix 8 of the CB2 receptor was synthesized chemically and its secondary structure determined by circular dichroism (CD) and (1)H NMR spectroscopy. NMR and CD revealed an alpha-helical structure in this region in both dodecylphosphocholine micelles and dimethylsulfoxide, in contrast to a random coil configuration found in aqueous solvent. This finding is in good agreement with other previous GPCR structural studies including X-ray crystallography. By combining our finding with other studies, we further hypothesize that the amphipathic nature of helix 8 can play a significant role in the function and regulation of CB receptors as well as other GPCRs in general.
Studies on the structure of the G-protein-coupled receptor rhodopsin including the putative G-protein binding site in unactivated and activated forms.
Activation of G-protein coupled receptors (GPCR) is not yet understood. A recent structure showed most of rhodopsin in the ground (not activated) state of the GPCR, but the cytoplasmic face, which couples to the G protein in signal transduction, was not well-defined. We have determined an experimental three-dimensional structure for rhodopsin in the unactivated state, which shows good agreement with the crystal structure in the transmembrane domain. This new structure defines the cytoplasmic face of rhodopsin. The G-protein binding site can be mapped. The same experimental approach yields a preliminary structure of the cytoplasmic face in the activated (metarhodopsin II) receptor. Differences between the two structures suggest how the receptor is activated to couple with transducin.
The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2.
Olig2, a basic helix-loop-helix (bHLH) transcription factor, is expressed in a restricted domain of the spinal cord ventricular zone that sequentially generates motoneurons and oligodendrocytes. Just prior to oligo-dendrocyte precursor formation, the domains of Olig2 and Nkx2.2 expression switch from being mutually exclusive to overlapping, and Neurogenins1 and 2 are extinguished within this region. Coexpression of Olig2 with Nkx2.2 in the spinal cord promotes ectopic and precocious oligodendrocyte differentiation. Both proteins function as transcriptional repressors in this assay. This effect is blocked by forced expression of Neurogenin1. By contrast, misexpression of Olig2 alone derepresses Neurogenins and promotes motoneuron differentiation. Olig2 therefore functions sequentially in motoneuron and oligodendrocyte fate specification. This dual action is enabled by spatio-temporal changes in the expression domains of other transcription factors with which Olig2 functionally interacts.
Pseudoreversion of the catalytic activity of Y14F by the additional substitution(s) of tyrosine with phenylalanine in the hydrogen bond network of delta 5-3-ketosteroid isomerase from Pseudomonas putida biotype B.
Delta5-3-ketosteroid isomerase (KSI) from Pseudomonas putida Biotype B catalyzes the allylic isomerization of Delta5-3-ketosteroids to their conjugated Delta4-isomers via a dienolate intermediate. Two electrophilic catalysts, Tyr-14 and Asp-99, are involved in a hydrogen bond network that comprises Asp-99 Odelta2...O of Wat504...Tyr-14 Oeta...Tyr-55 Oeta.Tyr-30 Oeta in the active site of P. putida KSI. Even though neither Tyr-30 nor Tyr-55 plays an essential role in catalysis by the KSI, the catalytic activity of Y14F could be increased ca. 26-51-fold by the additional Y30F and/or Y55F mutation in the hydrogen bond network. To identify the structural basis for the pseudoreversion in the KSI, crystal structures of Y14F and Y14F/Y30F/Y55F have been determined at 1.8 and 2.0 A resolution, respectively. Comparisons of the two structures near the catalytic center indicate that the hydrogen bond between Asp-99 Odelta2 and C3-O of the steroid, which is perturbed by the Y14F mutation, can be partially restored to that in the wild-type enzyme by the additional Y30F/Y55F mutations. The kinetic parameters of the tyrosine mutants with the additional D99N or D99L mutation also support the idea that Asp-99 contributes to catalysis more efficiently in Y14F/Y30F/Y55F than in Y14F. In contrast to the catalytic mechanism of Y14F, the C4 proton of the steroid substrate was found to be transferred to the C6 position in Y14F/Y30F/Y55F with little exchange of the substrate 4beta-proton with a solvent deuterium based on the reaction rate in D2O. Taken together, our findings strongly suggest that the improvement in the catalytic activity of Y14F by the additional Y30F/Y55F mutations is due to the changes in the structural integrity at the catalytic site and the resulting restoration of the proton-transfer mechanism in Y14F/Y30F/Y55F.
Low expression of p27(Kip1) in advanced mucoepidermoid carcinomas of head and neck.
BACKGROUND: p27(Kip1), a cyclin-dependent kinase inhibitor, negatively regulates the G1 phase progression of the cell cycle by binding to the cyclin E/cyclin-dependent kinase 2 complex. This study was done to investigate the expression of p27(Kip1) in mucoepidermoid carcinomas and its usefulness as an indicator in tumor progression, aggressiveness, and prognosis. METHODS: Thirty-one patients with mucoepidermoid carcinomas who had surgical resection were studied retrospectively. Clinicopathologic features, including histologic types, T stage, nodal status, perineural invasion, overall AJCC stage, and survival data, were obtained from medical records. Immunohistochemical staining with monoclonal antibodies against p27(Kip1) was performed on the formalin-fixed, paraffin-embedded specimens from each patient. The percentage of tumor cells expressing p27(Kip1) (labeling index) was evaluated by counting 1000 cells per slide in at least four different areas and comparing with the patients' clinicopathologic features and survival rates. RESULTS: Significant correlation was found between low p27(Kip1) expression and tumors with high-grade, advanced T stages, positive nodal status, and advanced clinical stages (p =.001 for all) except perineural invasion. Multivariate analysis indicated that p27(Kip1) expression (p =.030) was the most significant, and gender (p =.048) was the next significant predictor of overall survival among the variables. Also patients with low p27(Kip1) expression showed poor prognosis (p =.002). CONCLUSIONS: We suggest that p27(Kip1) is a reliable independent marker of tumor progression, invasiveness, and prognosis in the mucoepidermoid carcinomas.
Two cases of primary malignant melanoma of the lacrimal sac.
BACKGROUND: Malignancy of the lacrimal sac is rare, and primary malignant melanoma in this region is extremely rare. METHODS: We report two cases of malignant melanoma of the lacrimal sac presented with epiphora and a palpable mass in the medial canthal area. We performed radical surgery and radiation therapy. RESULTS: The light microscopic, immunohistochemical, and electron microscopic studies confirmed the diagnosis. One of the patients, a 65-year-old-woman, has no evidence of recurrence or distant metastasis 3 years after surgery and radiotherapy, whereas another patient, a 56-year-old man, died of distant metastasis 6 months after surgery and radiotherapy. CONCLUSIONS: We present two cases of malignant melanoma of the lacrimal sac that masqueraded as chronic dacryocystitis. Head and neck surgeons should be aware of this disease entity when encountered with patients with epiphora and mass in the medial canthal area.
Malignant triton tumor of the nasal cavity.
BACKGROUND: Malignant triton tumor is usually an aggressive sarcoma consisting of a malignant schwannoma with rhabdomyoblastic differentiation. However, malignant triton tumor of the nasal cavity is very rare. METHODS: A case report of a 38-year-old woman with polypoid mass, which bled easily in the right nasal cavity, and nasal obstruction is presented with a review of the literature pertaining to this unusual case. RESULTS: The malignant triton tumor was treated with wide surgical excision followed by radiation therapy. Histopathological diagnosis of the malignant triton tumor was made on the surgical specimen. The patient's postoperative course was unremarkable, and follow-up at 5 years reveals no evidence of disease. CONCLUSIONS: A malignant triton tumor in the nasal cavity is a rare disease. Head and neck surgeons should recognize the possibility of malignant triton tumor occurring in the nasal cavity.
Clinical analysis of voice change as a parameter of premenstrual syndrome.
We have evaluated the relationship between voice change and premenstrual syndrome (PMS) by comparing acoustic measurements made during the follicular phase and the premenstrual phase. Twenty-eight women were followed for 2 months for this study. Each participant was asked to produce an /a/ sound for 5 seconds at the midfollicular phase of the menstrual cycle and then 2-3 days before menstruation. Each voice sample was stored and analyzed by the Dr. Speech Science program. The voice data collected from all subjects during the two phases were compared. After that, the subjects were divided into a PMS-positive and PMS-negative group according to the criteria cited in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV); the voice data from each group were compared separately between the two phases. There was no significant difference in the acoustic parameters between the two phases in all subjects (N = 28). In the PMS-positive group (N = 16), jitter was significantly increased during the premenstrual phase compared to the follicular phase (p = 0.048). The patient's PMS score was not correlated with the severity of voice change. We conclude that the change of voice parameter was objectively identified in the PMS-positive group, therefore more careful voice habituation is required during the premenstrual phase in that group.
Structure and enzymology of Delta5-3-ketosteroid isomerase.
The three-dimensional structures of Delta5-3-ketosteroid isomerases from two different bacterial species have been determined. The structures reveal an unusually apolar active site, in which each of several competitive inhibitors of the enzyme are held by two hydrogen bonds with the general acids Tyr14 and Asp99, and by hydrophobic interactions. The hydrogen bond between the Tyr14 hydroxyl and the C3 oxyanion of a transition-state analog is a low-barrier hydrogen bond, as indicated by a highly deshielded nuclear magnetic resonance. Structural and other biochemical studies have enabled the proposal of a detailed catalytic mechanism for Delta5-3-ketosteroid isomerase and provided a major thrust towards understanding the mechanism not only in chemical terms but also in energetics terms.
Alteration of a single amino acid changes the substrate specificity of dihydroflavonol 4-reductase.
Many plant species exhibit a reduced range of flower colors due to the lack of an essential gene or to the substrate specificity of a biosynthetic enzyme. Petunia does not produce orange flowers because dihydroflavonol 4-reductase (DFR) from this species, an enzyme involved in anthocyanin biosynthesis, inefficiently reduces dihydrokaempferol, the precursor to orange pelargonidin-type anthocyanins. The substrate specificity of DFR, however, has not been investigated at the molecular level. By analyzing chimeric DFRs of Petunia and Gerbera, we identified a region that determines the substrate specificity of DFR. Furthermore, by changing a single amino acid in this presumed substrate-binding region, we developed a DFR enzyme that preferentially reduces dihydrokaempferol. Our results imply that the substrate specificity of DFR can be altered by minor changes in DFR.
Intrasaccular detachable platinum coil embolization for traumatic pseudoaneurysm treatment of a cavernous carotid artery.
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Intraductal papilloma of the parotid gland in a child.
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Inflammatory pseudotumor of the maxillary sinus.
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Expression of human beta-defensin 1 mRNA in human palatine tonsil.
Defensins are a newly delineated family of effector molecules whose contribution to host defense, inflammation and cytotoxicity may be considerable for humans. Beta-defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at the mucosal surface. Tonsillar epithelium, which is constantly exposed to microorganisms, may express these natural antibiotic peptides as part of its protective function. In this study we searched for the expression of hBD-1 mRNA in palatine tonsillar epithelium without signs of infection, using reverse transcriptase-polymerase chain reaction and in situ hybridization. Total RNA was isolated from non-infected tonsil and hBD-1 mRNA was identified in these tissues. From in situ hybridization, the expression of hBD-1 mRNA was seen to be localized in the surface epithelia of palatine tonsil. These data suggest that hBD-1 of the palatine tonsil may also play an important role in innate defense against microorganisms.
Isolation and characterization of the Candida albicans MOT2 gene.
A putative Candida albicans homologue of Saccharomyces cerevisiae MOT2 (modulator of transcription) has been cloned and analyzed. A cDNA fragment corresponding to a portion of S. cerevisiae MOT2 was used to isolate a similar C. albicans gene (CaMOT2). CaMOT2 is comprised of two exons of 50 bp and 1,714 bp, respectively, with a single 82 bp intron located near the 5' end of the gene. The gene encodes a protein (CaMot2p) with an estimated mass of 67 kDa. The 5' region of the gene shows sequence homology with S. cerevisiae MOT2, whereas no significant similarity was observed in the 3' region. Similarly, the N-terminal portion of C. albicans Mot2p exhibits approximately 80% homology with S. cerevisiae Mot2p, while no significant homology to any known protein was observed in the carboxy-terminal half of the C. albicans protein. The N-terminal portion of CaMot2p contains a cysteine-rich domain (amino acids 18-62). The distribution of the cysteine residues identifies CaMot2p as a zinc-finger protein. The data suggest two potential Zn-binding sites, similar to the arrangement found in S. cerevisiae. Reverse-transcriptase polymerase chain reaction was used to compare the level of CaMOT2 expression between C. albicans grown in vitro and growth during in vivo infection in the rat model of oral candidiasis. The results showed CaMOT2 is down-regulated during growth in the rat oral cavity compared to in vitro culture. Although the function of C. albicans MOT2 has not been determined, comparison to S. cerevisiae MOT2 suggests the gene product may act as a general negative regulator.
Korean students' differential attitudes toward people with disabilities: an acculturation perspective.
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