Comment on "Can one predict DNA transcription start sites by studying bubbles?".
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DNA↗
Biomedical subjects
C H Choi
Publications and source records attributed to C H Choi.
Increased expression of pAKT is associated with radiation resistance in cervical cancer.
Phosphorylated AKT (pAKT) is a major contributor to radioresistance in human cancers. The aim of this study was to investigate the association of pAKT expression and radiation resistance in cervical cancer. A retrospective review was made of the records of 27 women who received primary radiation therapy due to locally advanced cervical cancer (LACC) with FIGO stage IIB-IVA. Nine patients regarded as radiation resistant developed local recurrences with a median progression free interval of 9 months. Eighteen patients did not show local recurrences, and were regarded as a radiation-sensitive group. Using pretreatment paraffin-embedded tissues, we evaluated pAKT expression by immunohistochemistry. A significant association was found between the level of pAKT expression and local recurrence. Immunohistochemical staining for pAKT was significantly more frequent in the radiation-resistant than in the radiation-sensitive group (P=0.004). The mean progression-free survival was 86 months for patients with pAKT-negative staining (19 cases) and 44 months for patients with pAKT-positive expression (eight cases) (P=0.008). These results suggest that signalling from phosphatidylinositide 3-kinase/pAKT can lead to radiation resistance, and that evaluation of pAKT may be a prognostic marker for response to radiotherapy in LACC.
Adult↗
Healing length and bubble formation in DNA.
It has been suggested that thermally induced separations ("bubbles") of the DNA double-strand may play a role in the initiation of gene transcription, and an accurate understanding of the sequence dependence of thermal strand separation is therefore desirable. Based on the Peyrard-Bishop-Dauxois model, we show here that the bubble forming ability of DNA can be quantified in terms of a healing length L(n), defined as the length (number of base-pairs) over which a base-pair defect affects bubbles involving n consecutive base-pairs. The probability for a bubble of size n is demonstrated to be proportional to the number of adenine-thymine base-pairs found within this length. The method for calculating bubble probabilities in a given sequence derived from this notion requires several order of magnitude less numerical effort than direct evaluation.
Base Pairing↗
15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) induces cell death through caspase-independent mechanism in A172 human glioma cells.
15-Deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ(2)) is a naturally occurring cyclopentenone metabolite of prostaglandin D(2) (PGD(2)) and is known as a specific potent ligand for the peroxisome proliferators activator receptor-gamma (PPARgamma). 15d-PGJ(2) inhibits cell growth and induces apoptosis in a number of different cancer cells. However, the underlying mechanism by which 15d-PGJ(2) induces cell death remains to be defined. The present study was undertaken to determine the effect of 15d-PGJ(2) on cell death in A172 human glioma cells. 15d-PGJ(2) caused reactive oxygen species (ROS) generation. 15d-PGJ(2)-induced ROS production and cell death were prevented by the antioxidant N-acetylcysteine. Activation of mitogen-activated protein kinases (MAPK) was not observed in cells treated with 15d-PGJ(2 )and inhibitors of MAPK subfamilies also were not effective in preventing 15d-PGJ(2)-induced cell death. 15d-PGJ(2) treatment caused mitochondrial dysfunction, as evidenced by depolarization of mitochondrial membrane potential. 15d-PGJ(2) induced caspase activation at 24 h of treatment, but the 15d-PGJ(2)-induced cell death was not prevented by caspase inhibitors. The antiapoptotic protein XIAP levels and release of apoptosis inducing factor (AIF) into the cytosol were not altered by 15d-PGJ(2) treatment. Taken together, these findings indicate that 15d-PGJ(2) triggers cell death through a caspase-independent mechanism and ROS production and disruption of mitochondrial membrane potential play an important role in the 15d-PGJ(2)-induced cell death in A172 human glioma cells.
Brain Neoplasms↗
Elephantiasic thyroid dermopathy.
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BCG Vaccine↗
Use of lithium in the treatment of thyrotoxicosis.
OBJECTIVES: To evaluate the efficacy and safety of lithium in the treatment of thyrotoxicosis, and to study the dose and serum levels at which therapeutic response occurs. DESIGN: Retrospective study. SETTING: Thyroid clinic of a regional hospital in Hong Kong. PATIENTS: Thirteen patients with thyrotoxicosis pending therapy with radioiodine or surgery, in whom thionamides were contra-indicated due to adverse reactions or failure of treatment. MAIN OUTCOME MEASURES: Free thyroxine levels, time to euthyroidism, and side-effects of lithium. RESULTS: A satisfactory response, defined as a fall by 40% or more in free thyroxine levels and clinical improvement, was achieved in eight patients within 1 to 2 weeks of lithium therapy. In four others, response occurred in 3 to 5 weeks. Response was slow and inadequate in one patient due to 'escape'. The median dosage of lithium was 750 mg daily, with a range of 500 to 1500 mg daily. The median serum lithium level was 0.63 mmol/L. Lithium toxicity was observed in one patient. CONCLUSIONS: A relatively low dose of lithium offers a safe and effective alternative means of controlling thyrotoxicosis in patients who cannot tolerate or do not respond to thionamides.
Adolescent↗
Rerupture following endovascular treatment for dissecting aneurysm of distal anterior inferior cerebellar artery with parent artery preservation: retreatment by parent artery occlusion with Guglielmi detachable coils.
Distal anterior inferior cerebellar artery (AICA) aneurysms are rare and most cases have been treated surgically by clipping, wrapping or trapping. We recently treated this 20-year-old male patient by an endovascular technique. At first, he was treated by intra-aneurysmal embolisation with parent artery preservation. But he presented with rerupture 1 month after embolisation. Follow-up angiography revealed the regrowth of the aneurysm, which was considered as a dissecting aneurysm. We performed occlusion of the AICA just proximal to the aneurysm to prevent fatal rebleeding. He gradually improved and his level of consciousness fully recovered. At 2 year follow up, he had no neurological deficits. We suggest that embolisation of distal AICA aneurysm with parent artery occlusion may be safe and a simple method in the treatment of distal AICA aneurysms.
Adult↗
Metabolic stress regulates basic transcription through acetyl-coenzyme A.
The acetylation and auto-acetylation of general transcription factors has recently been demonstrated, but the functional significance of these modifications is unclear. The presence of acetyl-coenzyme A activates basal transcription, and acetylation of transcription factor IIB (TFIIB) has been shown to activate transcription in several contexts. If auto-acetylation is an important pathway in eukaryotes, the regulatory pathways for acetyl-coenzyme A should be important in transcription regulation. Fasting represents an acute metabolic stress which should elevate levels of acetyl-coenzyme A, while mitochondrial aging represents a cumulative stress. We show that tissue-specific levels of acetylated TFIIB change dramatically in response to fasting in mice, suggesting a role for metabolism in the direct regulation of transcription. We also observed a large increase in acetyl-TFIIB in tissues from aged mice relative to younger mice. Sir2 family deacetylases, which regulate acetyl-coenzyme A synthesis, have recently been shown to impart longevity in a variety of organisms through a pathway related to calorie restriction. We hypothesize that protein acetylation and Sir2-related deacetylation may be tied to the metabolic regulation of transcription through the availability and action of acetyl-coenzyme A on key transcription factors and transcriptional regulators.
Acetyl Coenzyme A↗
[Immunohistochemical localization of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in tuberculous pleuritis].
Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found by ELISA and gelatine zymography in different concentrations in pleural fluid in tuberculous (TB) pleuritis. For further differentiation MMP and TIMP were localized in pleural biopsies by immunhistochemical staining with antibodies directed against MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 using the Labelled-Avidin-Biotin (LAB). Immunohistological reactivity of MMP-1 was found in epitheloidcellular histiocytes, Langhans' giant cells, lymphocytes, macrophages, as well as in fibroblasts of granulomatous reactions. MMP-2 was found in a few epitheloid cellular histiocytes, fibroblasts, and inflammatory cells. MMP-3 was weakly positive in a few lymphocytes only. MMP-9 was found in a few fibroblasts, epitheloid cells, and inflammatory cells, foremost, however, in pleural mesothial cells. A few fibroblasts only showed immunoreactivity of TIMP-1 and TIMP-2. The observed inhomogenous staining pattern could be explained by the different state of activation of individual cellular units. In conclusion, the immunohistochemical demonstration of MMP and TIMP in pleural cells and tissue structures indicates their local involvement in fibrosing reactions in TB-pleuritis.
Female↗
Melanocytic and non-melanocytic oncocytic metaplasia of the nasopharynx.
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Aged↗
Hepatic myospherulosis complicating portal vein embolisation.
AIMS: Myospherulosis is a rare condition characterised by sac-like structures containing spheroid bodies in cysts or cystic spaces in the tissue. This condition has not previously been reported in the liver. The association with previous portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil and the proposed mechanism of pathogenesis are discussed. METHODS: Samples from 8 patients treated by hepatectomy after portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil were retrieved from the archives of the United Christian Hospital, Hong Kong. The histological specimens were reviewed. A panel of histochemical and immunohistochemical stains was used. RESULTS: All cases showed hepatic myospherulosis within the veins. The veins were denuded of endothelium, which was replaced by granulation tissue and fibrous tissue with a lymphoplasmacytic infiltrate. Foreign body-type giant cells (six cases) and eosinophilic infiltrates (seven cases) were noted in most cases. Both parent bodies and endobodies were stained red by Papanicolaou and Masson's trichrome and stained blue by solochrome cyanine. The endobodies showed immunoreactivity towards glycophorin A. They were negative for Alcian blue, periodic acid Schiff, Grocott, and Ziehl-Neelsen stains. CONCLUSIONS: The endobodies of myospherulosis may be misdiagnosed as fungi or algae by the unwary. The clinical history, intravascular location, lack of staining with periodic acid Schiff and Grocott stains, and positive glycophorin A staining are generally sufficient for a confident diagnosis of myospherulosis.
Aged↗
A case of oral myiasis due to Chrysomya bezziana.
Chrysomya bezziana is a causative agent of obligatory myiasis. We report the first case of human infestation of Chrysomya bezziana in Hong Kong in an 89-year-old woman who had previously had a stroke. One day after hospital admission for fever, a small fissure at the labial gingiva of the upper incisors and several ulcerative lesions at the hard palate were noticed during routine mouth care. A live maggot was seen protruding from the small fissure. In the following few days, a total of seven maggots were removed by forceps. Urgent computed tomography and magnetic resonance imaging of the oral cavity showed an ulcerative soft-tissue lesion over the anterior palate, with a fistula communicating to the labial gingiva. The tissue loss was limited to the bony margin of the hard palate. The infestation was managed by manual removal of maggots and surgical debridement. Medical personnel taking care of old or debilitated patients need to bear in mind the possibility of Chrysomya bezziana infestation to be able to make a prompt diagnosis and implement relevant intervention to prevent extensive tissue destruction.
Aged↗
Use of the low-dose corticotropin stimulation test for the diagnosis of secondary adrenocortical insufficiency.
OBJECTIVE: To assess the clinical utility and safety of the low-dose corticotropin stimulation test in the diagnosis of secondary adrenocortical insufficiency. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PARTICIPANTS: Seventy-two Chinese patients with suspected secondary adrenocortical insufficiency. MAIN OUTCOME MEASURE: Serum cortisol response during the low-dose corticotropin stimulation test, using the insulin tolerance test as the gold standard. RESULTS: The 30-minute cortisol level during the low-dose corticotropin stimulation test was most closely correlated (r=0.79) with the peak cortisol level achieved during the insulin tolerance test. The optimum sensitivity and specificity of the low-dose corticotropin stimulation test were obtained at a cut-off value of 550 nmol/L or more for the 30-minute cortisol level. Using the insulin tolerance test as the gold standard for comparison, the low-dose corticotropin stimulation test had a sensitivity of 97%, a specificity of 78%, a positive predictive value of 81%, and a negative predictive value of 97% at this cut-off value. The positive likelihood ratio was 4.4 and the negative likelihood ratio 0.04. CONCLUSION: The low-dose corticotropin stimulation test, using the cortisol response at 30 minutes after synacthen 1 microg is a safe, convenient, and sensitive method for screening abnormalities of the hypothalamic-pituitary-adrenocortical axis in Chinese patients suspected of having secondary adrenocortical insufficiency.
Adrenal Insufficiency↗
Double-edged sword of chemosensitizer: increase of multidrug resistance protein (MRP) in leukemic cells by an MRP inhibitor probenecid.
The multidrug resistance protein (MRP) is a drug efflux membrane pump conferring multidrug resistance to tumor cells. Clinical trials have been undertaken to improve the effectiveness of chemotherapy by adding an MRP inhibitor to the treatment regimen. This study attempted not only to determine novel resistance mechanisms in MRP-overexpressing AML cells (AML-2/DX100) by chronic exposure to doxorubicin in the presence of an MRP inhibitor probenecid but also to find out whether probenecid could increase MRP levels. AML-2/DXPBA cultured in the presence of probenecid (600 microM) and doxorubicin (100 ng/ml) showed a higher level of the multidrug resistance (MDR) phenotype when compared to AML-2/DX100. AML-2/DXPBA showed increased levels of MRP compared to those of AML-2/DX100. Probenecid increased the MRP levels without an increase in MRP mRNA in AML-2/WT in both a time- and dose-dependent manner. Of the MRP inhibitors including probenecid, ofloxacin, erythromycin, and rifampicin used in this study, only probenecid showed a marked chemosensitizing effect in AML-2/DX100 but not in HL-60/Adr, suggesting that the chemosensitizing effects of the MRP inhibitors vary according to the type of resistant cells. The maximum noncytotoxic concentrations of these MRP inhibitors increased the MRP levels to various degrees in both AML-2/WT and HL-60/WT. However, the chemosensitizing effects of the MRP inhibitors were not correlated with their MRP-increasing effects. Altogether, MRP inhibitors such as probenecid have been shown to function as a double-edged sword, indicating that they are not only an effective chemosensitizer of MRP-associated MDR tumor cells but also an MRP activator. Therefore caution should be taken whenever using MRP inhibitors to reverse MRP-mediated multidrug resistance in clinical cancer chemotherapy as well as when used to inhibit MRP expression in vitro.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Fungicidal effect of antimicrobial peptide, PMAP-23, isolated from porcine myeloid against Candida albicans.
The antifungal activity and mechanism of a 23-mer peptide, PMAP-23, derived from pig myeloid was investigated. PMAP-23 displayed strong antifungal activity against yeast and mold. To investigate the antifungal mechanism of PMAP-23, fluorescence activated flow cytometry and confocal laser scanning microscopy were performed. Candida albicans treated with PMAP-23 showed higher fluorescence intensity by propidium iodide(PI) staining, which was similar to that of Melittin than untreated cells. Confocal microscopy showed that the peptide was located in the plasma membrane. The action of peptides against fungal cell membranes was examined by treating prepared protoplasts of C. albicans with the peptide and lipid vesicle titration test. The result showed that the peptide prevented the regeneration of fungal cell walls and induced release of the fluorescent dye trapped in the artificial membrane vesicles, indicating that the peptide exerts its antifungal activity by acting on the plasma lipid membrane.
Amino Acid Sequence↗
Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients.
BACKGROUND: Though the dysfunction of central dopaminergic system has been proposed, the etiology or pathogenesis of schizophrenia is still uncertain partly due to limited accessibility to dopamine receptor. The purpose of this study was to define whether or not the easily accessible dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia. RESULTS: 44 drug-medicated schizophrenics for more than 3 years, 28 drug-free schizophrenics for more than 3 months, 15 drug-naïve schizophrenic patients, and 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of D3 and D5 dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors was compared in each group. After taking antipsychotics in drug-free and drug-naïve patients, the dopamine receptors of peripheral lymphocytes were sequentially studied 2nd week and 8th week after medication. In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes significantly increased compared to that of controls and drug-medicated schizophrenics, and D5 dopamine receptor mRNA expression increased compared to that of drug-medicated schizophrenics. After taking antipsychotics, mRNA of dopamine receptors peaked at 2nd week, after which it decreases but the level was above baseline one at 8th week. Drug-free and drug-naïve patients were divided into two groups according to dopamine receptor expression before medications, and the group of patients with increased dopamine receptor expression had more severe psychiatric symptoms. CONCLUSIONS: These results reveal that the molecular biologically-determined dopamine receptors of peripheral lymphocytes are reactive, and that increased expression of dopamine receptor in peripheral lymphocyte has possible clinical significance for subgrouping of schizophrenis.
Journal Article↗
Pyogenic spondylitis in an S1-S2 immobile segment.
STUDY DESIGN: A case of pyogenic spondylitis in S1-S2 is presented. OBJECTIVE: To describe the diagnosis and management of this rare spondylitis. SUMMARY OF BACKGROUND DATA: The segment including the first and second sacral vertebrae is not mobile. Therefore, discitis of S1-S2 and adjacent spondylitis is very rare. To the authors' knowledge, this is the first reported case of infectious spondylitis in an immobile segment: S1-S2. METHODS: In addition to radiography and bone scintigraphy, magnetic resonance imaging was used to confirm the diagnosis. Changes consistent with infectious spondylitis were shown, including an epidural abscess. RESULTS: The patient was treated with laparoscopic drainage and biopsy. Staphylococcus aureus was cultured, and adequate antibiotics were administered. Repeat magnetic resonance imaging at approximately 4 months demonstrated normal signal intensity and disappearance of the abscess. CONCLUSION: Findings from this study show that pyogenic spondylitis can occur in immobile S1-S2.
Adolescent↗
Down-regulation of catalase gene expression in the doxorubicin-resistant AML subline AML-2/DX100.
A major obstacle to successful cancer chemotherapy is the development of multidrug resistance (MDR). The previous study revealed that a doxorubicin-resistant AML subline (AML-2/DX100) overexpressed an MDR-associated protein (MRP) but not P-glycoprotein. The AML-2/DX100 also showed various levels of resistance to daunorubicin and vincristine but was paradoxically sensitive to hydrogen peroxide (5-fold), t-butyl hydroperoxide (3-fold), and paraquat (2-fold) when compared to the drug-sensitive parental AML-2 cells (AML-2/WT). We compared the activities of antioxidant enzymes to detoxify reactive oxygen species (ROS), including superoxide dismutases, glutathione S-transferase, catalase, glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase in both AML-2/WT and AML-2/DX100. Interestingly, of these antioxidant enzymes, catalase activity of AML-2/DX100 decreased significantly to about one-third that of AML-2/WT (P < 0.000005). The decreased activity of catalase was due to reduced expression of the catalase gene; confirmed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses. The decreased activity of catalase was maintained even in the absence of doxorubicin for 3 months as well as by the treatment of probenecid, an MRP inhibitor. In addition, there was no difference in catalase activity between HL-60 and another MRP-overexpressing subline HL-60/Adr. Taken together, the paradoxical increase in the sensitivity of an MRP-overexpressing AML-2/DX100 in response to peroxides and paraquat is due to the down-regulation of catalase gene expression, which totally independent of overexpression of MRP. It is therefore possible that decreased catalase activity could be exploited as an Achilles' heel in resistant cells such as this.
ATP Binding Cassette Transporter, Subfamily B, Mem↗