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Biomedical subjects

C Kuo

Publications and source records attributed to C Kuo.

At least 19 recordsLinked to original sources

15-year outcome of treated bipolar disorder.

BACKGROUND: Prior reports suggested that bipolar patients in Taiwan had comparable long-term outcome to Western patients despite markedly lower rates of co-occurring substance use disorders. Thus, predictors of long-term outcome identified from Taiwanese bipolar samples may be less influenced by substance abuse. METHODS: One hundred and one patients with bipolar disorder (DSM-III-R) having been naturalistically treated for at least 15 years were recruited. These patients were annually followed for 2 years to assess overall outcome, psychiatric symptoms, rehospitalization, work, and social adjustment. A combination of medical record reviews and direct personal interviews with patients and family members provided the clinical data. RESULTS: Of these patients, 16.8% expressed a poor overall long-term outcome, even though only two (2.0%) patients exhibited alcohol dependence during the follow-up period. Multivariate regression showed that full compliance with medication was the strongest predictor of favorable overall long-term outcome, followed by younger age at onset and male sex. Younger age at onset as well as male sex, but not full compliance, also predicted a favorable psychosocial outcome. LIMITATIONS: Recruiting our sample from a clinical population with uncontrollable long-term treatment limits the generalizability of the findings. CONCLUSIONS: Compliance with pharmacotherapy is important to achieve a favorable overall long-term outcome of bipolar disorder. A portion of bipolar patients may have an unfavorable psychosocial outcome regardless of the psychopharmacological intervention or presence of substance abuse.

Adult↗

Molecular strategy for detecting metastatic cancers with use of multiple tumor-specific MAGE-A genes.

BACKGROUND: The human melanoma-associated antigen family A (MAGE-A) has high specificity and expression in various malignancies, but individual family members are expressed at low frequency in any one particular type of cancer. We therefore developed a method to detect mRNAs from multiple MAGE-A genes in a single reaction. METHODS: Universal MAGE-A (uMAGE-A) primers and probe were designed to reverse-transcribe, amplify, and detect by electrochemiluminescence (ECL) MAGE-A mRNAs on the Origen Analyzer. The assay was performed on total RNA of melanoma (n = 9 cell lines and 24 tumors), breast cancer (n = 7 and 26), and colorectal cancer (CRC; n = 5 and 12). We also evaluated blood from melanoma (n = 50), breast cancer (n = 16), and CRC (n = 21) patients. RESULTS: The uMAGE-A mRNA was detectable in 0.01-1 ng of cell line RNA. The identity of the uMAGE-A cDNA products was confirmed by sequencing and polyacrylamide gel electrophoresis. The uMAGE-A assay increased detection of melanoma, breast cancer, and CRC tumor by 13%, 31%, and 25%, respectively, compared with a MAGE-A1 assay, and by 17%, 19%, and 25%, respectively, compared with a MAGE-A3 assay. The uMAGE-A assay detected circulating tumor cells in the blood of melanoma (24%), breast cancer (25%), and CRC (29%) patients. CONCLUSIONS: The uMAGE-A reverse transcription-PCR/ECL assay provides a practical and sensitive approach for detection of various metastatic cancers in tissues and blood.

Antigens, Neoplasm↗

Rapid ocular angiogenic control via naked DNA delivery to cornea.

PURPOSE: To determine the efficacy and safety of naked plasmid gene therapy to the corneal stroma and epithelium. METHODS: Naked plasmid DNA was injected under pressure into the cornea of mice. The expression of genes coding for beta galactosidase (beta-gal), enhanced green fluorescent protein (EGFP), vascular endothelial growth factor (VEGF), and soluble Flt-1 (s-Flt) was recorded and measured with regard to dose, time course, and bioactivity. RESULTS: LacZ gene expression of the protein beta-gal was demonstrated as early as 1 hour, with expression persisting for 10 days. Plasmid-injected corneas remained clear and free of inflammation. EGFP was bicistronically expressed with VEGF to demonstrate the practicality of simultaneous in vivo analysis of gene expression and growth factor bioactivity. Corneal injection of a plasmid containing VEGF cDNA induced corneal and anterior chamber neovascularization. Moreover, corneal injection of plasmid containing the cDNA for the soluble form of the VEGF receptor Flt-1 effectively prevented corneal neovascularization. CONCLUSIONS: The cornea is readily accessible for gene therapy in the laboratory and in the clinic. The method described is safe, effective, titratable, and easily monitored. Naked DNA delivery to the cornea has the potential to alter the treatment of a wide variety of corneal and anterior segment diseases.

Animals↗

Molecular markers in blood as surrogate prognostic indicators of melanoma recurrence.

Improvement is needed in the ability to evaluate the prognosis of melanoma patients who are clinically disease-free but likely to develop recurrent metastatic disease. The detection of circulating melanoma cells in blood is a potential surrogate marker of subclinical residual disease. We assessed the prognostic clinical utility of a multimarker melanoma reverse transcriptase-PCR (RT-PCR) assay using blood of 46 patients who were clinically disease-free. All patients were followed up for more than 4 years for disease recurrence. There was a significant correlation between number of RT-PCR markers present in blood and American Joint Committee on Cancer stage (P = 0.009). The number of RT-PCR markers detected in blood was an independent prediction factor of disease recurrence in a Cox proportional hazard model (P = 0.02). A risk factor model using American Joint Committee on Cancer stage and number of positive RT-PCR markers significantly predicted disease recurrence in 2, 3, and 4 years of follow-up. These studies demonstrate that molecular detection of circulating melanoma cells may be of significant prognostic value in determining early disease recurrence and may be useful for stratifying patients for adjuvant therapy.

Biomarkers, Tumor↗

Puralpha, a single-stranded DNA binding protein, suppresses the enhancer activity of cAMP response element (CRE).

Puralpha, a single-stranded DNA binding protein, recognizes a PUR element (GGN repeat). We have reported that Puralpha binds to a single-stranded oligonucleotide probe containing the cAMP response element (CRE) of rat somatostatin gene using a gel mobility shift assay. Here, we showed that Puralpha binds to the probe only in the presence of a PUR element by a more detailed characterization. We also examined the effects of Puralpha on the enhancer activity of the somatostatin CRE in PC12 cells using the reporter gene assay. Transfected Puralpha suppressed the CRE enhancer activity stimulated by forskolin (which increases intracellular cAMP), but suppression was not observed when the PUR element was deleted. The neurite extension induced by forskolin was inhibited by the transfection of Puralpha, but that by NGF was not suppressed. The c-fos mRNA induced by forskolin, but not by NGF, was also suppressed by Puralpha transfection. These results indicate that Puralpha suppresses the biological activities induced by forskolin, but not by NGF, in PC12 cells and that Puralpha could interfere with a cAMP-CRE signal pathway.

Animals↗

Molecular detection of metastatic pancreatic carcinoma cells using a multimarker reverse transcriptase-polymerase chain reaction assay.

BACKGROUND: The diagnosis of pancreatic carcinoma is often associated with a poor prognosis, because most patients already have advanced disease. A highly sensitive assay to detect the progression of pancreatic carcinoma would be of significant clinical utility. The authors developed multiple tumor mRNA markers for reverse transcriptase-polymerase chain reaction (RT-PCR) to detect metastatic tumor cells in the blood and tissue of patients with American Joint Committee on Cancer (AJCC) Stage II/III or IV pancreatic carcinoma. METHODS: An RT-PCR plus Southern blot assay was used to detect mRNA of tumor markers in blood and tissues. mRNA expression of the tumor progression markers MET (hepatocyte growth factor receptor gene c-met), GalNAc-T (beta1,4- N-acetyl-galactosaminyl-transferase), and beta-hCG (beta-human chorionic gonadotropin) was evaluated in 9 pancreatic carcinoma cell lines, 13 tumor biopsy specimens, 5 nonmalignant pancreatic tissue specimens, and blood from 33 pancreatic carcinoma patients and 32 healthy donors. RESULTS: The detection limit of the assay was 1 rhog, 10 rhog, and 10 rhog for MET, GalNAc-T, and beta-hCG mRNA expression, respectively. The pancreatic carcinoma cell lines expressed all three mRNA markers. Of blood specimens from 17 patients with AJCC Stage IV pancreatic carcinoma, 82%, 65%, and 76% were MET, GalNAc-T, and beta-hCG mRNA positive, respectively. Of blood specimens from 16 patients with AJCC Stage II/III disease, 88% were positive for at least 1 mRNA marker. CONCLUSIONS: A multiple molecular marker assay was developed to detect cancer cells in blood and tissue from patients with different stages of pancreatic carcinoma. The detection of cancer cells in the blood may be used as a marker of pancreatic tumor progression and may be useful in monitoring response to therapy.

Antigens, Neoplasm↗

Factor structure of trunk performance data for healthy subjects.

OBJECTIVE: To examine the factor structure of various measurements of trunk muscle performance for healthy subjects. DESIGN: A total of 22 performance scores were collected and their univariate and multi-variate relationships were examined. BACKGROUND: Extensive literature exists on the measurement of trunk performance data and the relationships between measurements but what needs to be collected to realize a true performance score remains unclear. METHODS: Trunk muscle performance scores of 150 subjects (71 males and 79 females) were obtained on an Isostation B-200 Dynamometer. Twenty-two parameters measuring range of motion, isometric strength, velocity, and endurance on all three planes of motion were collected. The factor structures were constructed using Principal Components Analysis. RESULTS: Clear-cut factor patterns (explained 96.3% of the total variance) suggests that the five-factor structure might be valid and appropriate for this population. The major loading on each factor indicated that: Factor 1 could be labeled as a static strength measure; Factor 2 as velocity; Factor 3 as flexibility; and Factors 4 and 5 as fatigue-resistance. CONCLUSIONS: No single mode of measurement can provide a good representation of a total trunk muscle performance. RelevanceFor the realization of trunk muscle performance, clinics have to measure all modes of isometric strength, velocity, range of motion, and endurance. Care must be taken in eliminating any parameter.

Adult↗

Detection of Chlamydia pneumoniae in arterial tissues.

In literature in which detection of Chlamydia pneumoniae in the artery is described, the methods used were immunocytochemistry (ICC), polymerase chain reaction (PCR), electron microscopy, and isolation. These studies demonstrated the presence of the organism in atheromatous lesions. The organism was detected frequently by ICC and PCR in atheromatous tissues (approximately 50% of subjects) but rarely in normal arteries (approximately 1% of subjects). There has been poor correlation between detection and serology. Detection studies have been used to assess the etiologic role of C. pneumoniae in atherosclerosis and to determine whether C. pneumoniae infection contributes to acute cardiovascular events. Although these studies produced suggestive evidence of an etiologic role, the use of observational studies to obtain a definitive answer is difficult. Therefore, investigators are increasingly concentrating their efforts on studies that use animal models, in vitro cultured arterial cells, and therapeutic trials in humans to determine the pathogenic role of the organism in atherosclerosis.

Adolescent↗

Chlamydia, inflammation, and atherogenesis.

Atherosclerotic lesions are initiated and progress largely as a result of a chronic, fibroproliferative, inflammatory response. This review discusses how Chlamydia pneumoniae could conceivably contribute to this chronic inflammatory response and reports on recent in vivo and in vitro studies. In vivo studies in mice demonstrate that C. pneumoniae infection is disseminated to the artery wall following infection in the lung by alveolar macrophages. Recent in vitro studies show that infected U937 cells can directly transfer infection to endothelial cells and can indirectly increase the susceptibility of endothelial cells to C. pneumoniae infection. Loading of RAW 264.7 cells with modified forms of low-density lipoprotein increases the resistance of the cells to C. pneumoniae infection and also increases the susceptibility to the combined toxic effects of modified lipids and C. pneumoniae infection.

Animals↗

Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma.

Chlamydia pneumoniae is commonly detected in atherosclerotic plaque but the frequency of detection in non-cardiovascular (CV) tissues has not been well determined. In this study, archival autopsy tissue specimens from both CV and non-CV sites from 38 patients were tested by polymerase chain reaction and immunocytochemistry to detect C. pneumoniae. In addition, 33 surgical granuloma biopsy specimens were also tested. C. pneumoniae was detected most frequently in coronary artery tissue (34%) but was also detected in specimens from lung (13%), liver (10%), spleen (5%), bone marrow (10%), and lymph node (8%). The organism was detected in 3 of 33 granuloma specimens. These findings suggest that C. pneumoniae demonstrates a tropism for CV tissues and is either not widely distributed to non-CV tissues or does not persist chronically in those tissues after initial infection.

Arteries↗

Mouse models of C. pneumoniae infection and atherosclerosis.

Mouse models were used to determine whether Chlamydia pneumoniae establishes chronic infection of the aorta and contributes to atherogenesis. Persistent infection of the aorta occurred in 11 of 31 hyperlipidemic apolipoprotein E-deficient (apoE(-/-)) mice but not in C57BL/6J mice fed a normal diet after a single inoculation and in both models following repeated inoculation with C. pneumoniae. Repeated inoculation of C57BL/6J mice resulted in inflammatory changes in the heart and aorta in 8 of 40 of mice; however, no atherosclerotic lesion development was observed. Repeated inoculation of apoE(-/-) mice resulted in a statistically significant increase in lesion area (n=43; P=.05). Although Chlamydia trachomatis disseminated to the aorta, persistent infection was not established and no statistically significant increase in lesion area occurred. These studies suggest that persistent infection of the aorta can lead to inflammatory changes in the absence of hyperlipidemia and accelerate lesion progress in concert with hyperlipidemia.

Animals↗

Chlamydia pneumoniae induces inflammatory changes in the heart and aorta of normocholesterolemic C57BL/6J mice.

Chlamydia pneumoniae infection induces inflammatory changes in blood vessels in normocholesterolemic rabbits, but it is not known whether the same phenomenon occurs in other animal models. Thus, in this study, C57BL/6J mice were inoculated with C. pneumoniae. Inflammatory changes in the heart or aorta were observed in a small number of chronically infected mice. No evidence of atherosclerotic lesions was found in any of the mice. These findings suggest that chronic C. pneumoniae infection can induce inflammatory changes in the heart and aorta of C57BL/6J mice, but does not initiate definitive atherosclerosis.

Animals↗

Establishing preference for lidocaine solution to water: comparison between a fading and an abrupt-removal procedure for withdrawing a compound vehicle.

Rats were exposed to daily, 3-h, fixed-time 1-min food-pellet delivery sessions, which is a procedure that produces overdrinking (schedule-induced polydipsia). In previous polydipsia studies, rats came to prefer solutions of drug or non-drug agents to concurrently presented water if the agents had first been offered in a glucose-saccharin vehicle that was slowly eliminated (faded), leaving a choice between a substance in water vehicle vs water. In the first experiment, a more rapid vehicle-fading procedure was used to produce a preference for 0.19mg/ml lidocaine to water. In the second experiment, the vehicle was abruptly changed to water, which also resulted in a strong preference for lidocaine solution, although the lidocaine solution volumes ingested for the final sessions were significantly less than in the first experiment. The results are consistent with a conditioned flavor/nutrient preference interpretation for the institution of the lidocaine preference in both experiments. Although flavor/nutrient conditioning can be a sufficient condition for generating a substance preference, a previous experiment showed that it was not a necessary condition.

Anesthetics, Local↗

Effect of meconium aspiration on plasma endothelin-1 level and pulmonary hemodynamics in a piglet model.

Sequential changes in plasma endothelin-1 (ET-1) and pulmonary hemodynamics were studied in a piglet model of meconium aspiration syndrome (MAS). Sixteen piglets were randomly divided into meconium (MEC) and normal saline (NS) groups (8 animals/group). The animals of the MEC group were instilled with meconium (20% in normal saline) via an endotracheal tube (3 ml/kg), and the animals of the NS group instilled with the same amount of normal saline. The plasma ET-1 as well as pulmonary mechanics, arterial blood gas and hemodynamics were measured at baseline and 60, 120, 180 and 240 min after instillation. The results showed that plasma ET-1 level of the MEC group was significantly higher after meconium aspiration as compared with NS group (p < 0.05 at 60 and 120 min, p < 0.01 at 180 and 240 min). Furthermore, pulmonary vascular resistance (PVR) increased and remained elevated after 120 min (p < 0.01) and pulmonary artery pressure (PAP) increased after 180 min (p < 0.01). The correlation was significant between ET-1 and PVR (r = 0.92, p < 0.001) as well as ET-1 and PAP (r = 0.89, p < 0.001). These data suggest that elevation of ET-1, which has long-lasting vasoconstriction effect, may play an important role of pulmonary hypertension of MAS.

Animals↗

Is infection with Chlamydia pneumoniae a causative agent in atherosclerosis?

There is mounting evidence to suggest that Chlamydia pneumoniae might play a role in atherosclerosis. Serological studies and detection of the microorganism in atheromatous lesions were the first indications of an association between C. pneumoniae and the disease. Studies suggest that anti-chlamydial chemotherapy has a favorable effect on cardiovascular disease in humans. Moreover, infection of animals with C. pneumoniae induces inflammatory changes in the aorta that are suggestive of atherosclerosis and accelerates the progression of existing atherosclerotic lesions. If the pathogenic role of C. pneumoniae in atherosclerosis is defined more conclusively by future studies, the development of preventive or therapeutic measures against infection might provide an effective strategy to reduce the risk of atherosclerosis.

Animals↗