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S H Cheng

Publications and source records attributed to S H Cheng.

At least 73 records · Page 4Linked to original sources
PubMed1999

A pilot study of three-dimensional conformal radiotherapy in unresectable hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to determine the potential role of three-dimensional (3-D) conformal radiotherapy (RT) in treatment of unresectable hepatocellular carcinoma (HCC). METHODS: Thirteen patients were included in this study, which was conducted between 1993 and 1996. Nine patients (group A) were treated with 3-D conformal RT alone because of main portal vein thrombosis, inferior vena cava thrombosis, obstructive jaundice and failure of previous transcatheter arterial chemoembolization (TACE) to control the disease. The remaining four patients (group B) were treated with a combination of TACE and 3-D conformal RT. RESULTS: The greatest dimension of the main tumour in the whole group of patients ranged from 6 to 25 cm (median 15 cm). The radiation dose ranged from 40 to 60 Gy. The tumour response was evaluated by computed tomography scans of the liver 6-8 weeks after completion of radiotherapy. Partial response was observed in 58% of the patients (seven of 12) and minimal response in another 25% of patients (three of 12). One patient could not be evaluated because of the development of hepatic failure 1 month after completion of RT. All patients in group B lived for more than 1 year (range 16-40 months). In group A, one patient who had a large tumour (11 x 10 x 21 cm) with portal vein thrombosis was converted to become resectable after 45 Gy of radiation. The resection specimen revealed no residual cancer cells. This patient is alive longer than 15 months after treatment without the evidence of disease. CONCLUSIONS: Our experience indicates that HCC is more radiosensitive than it was traditionally expected. Three-dimensional reconstruction of tumour and surrounding organs helps to avoid excessive exposure of the liver and adjacent organs to RT and makes it a safer treatment modality for unresectable HCC. Our preliminary data show promise and are worthy of further study to explore the potential role of radiotherapy in the treatment strategy for HCC at various stages of involvement.

Aged↗
PubMed1999

Troponin-I, myoglobin, and mass concentration of creatine kinase-MB in acute myocardial infarction.

Myoglobin, creatine kinase-MB (CKMB) mass concentration and troponin-I are newer biochemical markers for the diagnosis of acute myocardial infarction (AMI). We conducted a prospective study to formulate a model for the collective interpretation of these three markers in the diagnosis of AMI. Eighty-seven patients with AMI had serial serum samples taken to establish the time-frame sensitivity of individual markers. None of the markers had a good sensitivity within the first 4 h of infarction. Myoglobin and CKMB (mass) had sensitivities of 92.3% and 96.2%, respectively, at 4-8 h post infarct. CKMB (mass) and troponin-I had sensitivities >92% at 8-24 h. Troponin-I maintained sensitivity >93% until 72 h. A guideline was formulated based on the results. Our data suggest that troponin-I, myoglobin and CKMB (mass) yield satisfactory diagnostic sensitivity when used with reference to specific time frames. The combined use of these markers can provide valuable information for clinicians in managing AMI patients.

Adult↗
PubMed1999

Nitric oxide inhibits heterologous CFTR expression in polarized epithelial cells.

Nitric oxide (. NO) has been implicated in a wide range of autocrine and paracrine signaling mechanisms. Herein, we assessed the role of exogenous. NO in the modulation of heterologous gene expression in polarized kidney epithelial cells (LLC-PK(1)) that were stably transduced with a cDNA encoding human wild-type cystic fibrosis transmembrane conductance regulator (CFTR) under the control of a heavy metal-sensitive metallothionein promoter (LLC-PK(1)-WTCFTR). Exposure of these cells to 125 microM DETA NONOate at 37 degrees C for 24 h (a chemical. NO donor) diminished Zn(2+)-induced and uninduced CFTR protein levels by 43.3 +/- 5.1 and 34.4 +/- 17.1% from their corresponding control values, respectively. These changes did not occur if red blood cells, effective scavengers of. NO, were added to the medium. Exposure to. NO did not alter lactate dehydrogenase release in the medium or the extent of apoptosis. Coculturing LLC-PK(1)-WTCFTR cells with murine fibroblasts that were stably transduced with the human inducible. NO synthase cDNA gene also inhibited CFTR protein expression in a manner that was antagonized by 1 mM N(G)-monomethyl-L-arginine in the medium. Pretreatment of LLC-PK(1)-WTCFTR with ODQ, an inhibitor of guanylyl cyclase, did not affect the ability of. NO to inhibit heterologous CFTR expression; furthermore, 8-bromo-cGMP had no effect on heterologous CFTR expression. These data indicate that. NO impairs the heterologous expression of CFTR in epithelial cells at the protein level via cGMP-independent mechanisms.

3T3 Cells↗
PubMed1999

Restoration of cyclic adenosine monophosphate-stimulated chloride channel activity in human cystic fibrosis tracheobronchial submucosal gland cells by adenovirus-mediated and cationic lipid-mediated gene transfer.

In human airways, the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is predominantly expressed in serous cells of the tracheobronchial glands. Despite considerable evidence that submucosal glands are important contributors to the pathophysiology of CF lung disease, most attempts at CFTR gene transfer have primarily targeted airway surface epithelial cells. In this study, we systematically evaluated CFTR gene transfer into cultures of immortalized CF human tracheobronchial submucosal gland (6CFSMEO) cells using adenovirus and cationic lipid vectors. We found that the efficiency of adenovirus-mediated gene transfer was comparable in 6CFSMEO and CFT1 cells (a surface airway epithelial cell line isolated from a subject with CF). So was the ranking order of adenovirus vectors containing different enhancers/promoters (CMV >> E1a approximately phosphoglycerokinase), as determined by both X-Gal staining and quantitative measurement of beta-galactosidase activity. Further, we provide the first demonstration that cationic lipids mediate efficient gene transfer into 6CFSMEO cells in vitro. The transfection efficiency at optimal conditions was higher in 6CFSMEO than in CFT1 cells. Finally, either infection with adenoviral vectors or transfection with cationic lipid:plasmid DNA complexes encoding CFTR significantly increased chloride (Cl-) permeability, as assessed using the 6-methoxy-N-(3-sulfopropyl)-quinolinium (SPQ) fluorescence assay, indicating restoration of functional CFTR Cl- channel activity. These data show that although the mechanisms of transfection may be different between the two cell types, 6CFSMEO cells are as susceptible as CFT1 cells to transfection by adenoviral and cationic-lipid gene transfer vectors.

Adenoviridae↗
PubMed1999

Antimicrobial susceptibility of Clostridium difficile by E test.

The in vitro inhibitory activity of 11 antimicrobials against 44 clinical isolates of Clostridium difficile was investigated. Minimum inhibitory concentrations (MICs) were determined using E test. Metronidazole (MIC90 0.38 microg/mL), teicoplanin (MIC90 0.75 microg/mL) and vancomycin (MIC90 1.0 microg/mL) were very active against the isolates examined, whereas, resistance to imipenem, cefoxitin, clindamycin and ciprofloxacin was found in most of the tested strains. We concluded that teicoplanin warrants clinical trials to determine its adequate dosage to treat C. difficile infection. The commonly used regimens to treat intra-abdominal and/or anaerobic infections (eg. imipenem, cefoxitin, clindamycin or ciprofloxacin) need special attention, while considering the side effects of C. difficile-associated diarrhea.

Ampicillin↗
PubMed1998

Efficiency of cationic lipid-mediated transfection of polarized and differentiated airway epithelial cells in vitro and in vivo.

Systematic analysis of a large number of different cationic lipids has led to the identification of novel structures (GL-67) and formulations of cationic lipid:plasmid DNA (pDNA) complexes that facilitate high levels of gene expression in lungs of mice. However, despite significant improvement in gene transfer activity, we show here that the efficiency of GL-67-mediated gene transduction of intact airway epithelia is still relatively low. Administration of GL-67:pCF1-CFTR (encoding the cystic fibrosis transmembrane conductance regulator) complexes into the nasal epithelium of cystic fibrosis (CF) transgenic mice resulted only in marginal correction of the ion transport defects. Measurements of nasal potential differences (PD) showed no correction of the sodium (Na+) transport defect, and only partial restitution of the chloride (Cl-) transport defect was achieved in a small proportion of the animals after perfusion of the nasal epithelium with the complexes. Furthermore, in contrast to results obtained following instillation of GL-67:pDNA complexes into the lungs of mice, perfusion of GL-67:pDNA into the nasal epithelium resulted only in a moderate enhancement of gene transduction activity relative to that attained with naked pDNA alone. To determine the basis for this low efficiency of transfection, a series of studies was conducted to identify some of the barriers governing cationic lipid-mediated gene transfer to the airway epithelium. We show here that the transfection activity of GL-67 was affected by the polarization, differentiation, and proliferative state of the cells. Diminished transfection activity was observed with nonmitotic, highly polarized and differentiated airway epithelial cells. This observed reduction in gene expression with nonmitotic cells was determined to be due in part to inefficient nuclear translocation of the pDNA from the cytoplasm. Together these data indicate that much improvement in the ability of cationic lipids to transfect polarized and differentiated airway epithelial cells is a necessary prerequisite for effective cationic lipid-mediated gene therapy of airway diseases such as CF.

Animals↗
PubMed1998

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy.

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.

Adult↗
PubMed1998

Potentiation of gene transfer to the mouse lung by complexes of adenovirus vector and polycations improves therapeutic potential.

Recombinant adenovirus (Ad) vectors are being considered for in vivo delivery of various therapeutic genes. One limiting factor in the development of Ad-based gene therapy is the low efficiency of gene transfer to target tissues such as vascular endothelium, smooth muscle, and airway epithelium. Complexing Ad vector with various polycations has been shown to enhance transduction of cell lines otherwise resistant to Ad infection in vitro. On the basis of this observation, the activity of Ad/polycation complexes was tested in vivo in the mouse lung. The results indicated that several polycations were capable of enhancing transduction of mouse respiratory epithelium, leading to a 1-2 log increase in levels of transgene expression. Poly-L-lysine (PLL) and DEAE-dextran were examined further and were found to increase Ad-mediated gene transfer without any additional toxicity as assessed histologically or through the measurement of inflammatory cytokines in bronchoalveolar lavages. The two polycations also failed to affect the humoral response against Ad vector and were themselves nonimmunogenic under conditions leading to enhanced gene transfer. Moreover, the ability to use reduced doses of vector complexed with polycations resulted in lower levels of Ad-specific antibodies and, thereby, improved readministration of vector. These results suggest that complexing Ad vectors with polycations has the potential to improve the therapeutic index by increasing transgene expression while reducing unwanted responses associated with high doses of vector.

Adenoviridae↗
PubMed1998

Diagnostic thoracic-computed tomography in radiotherapy for loco-regional recurrent breast carcinoma.

PURPOSE: This study was initiated to evaluate whether pretreatment diagnostic thoracic CT scan was useful for patients with loco-regional recurrent breast carcinoma, and to assess its impact on the design of radiotherapeutic treatment. METHODS AND MATERIALS: Between March 1991 and January 1997, 44 patients underwent thoracic CT examination with contrast material before the consideration of radiotherapy for their isolated loco-regional recurrent breast carcinoma. The CT radiographs were prospectively reviewed for additional findings clinically undetected by prior physical examination and plain-chest radiograph. The changes made in treatment design and dosage of radiation as a result of CT findings were recorded for analysis. The correlation between prognostic indicators and the CT findings was also studied. RESULTS: Twenty-two of 44 (50%) patients were found to have additional abnormalities detected only after thoracic CT examinations were performed. The strategy of radiation therapy was altered in 17 of 22 (77%) patients as a result. Patients with shorter disease-free interval (p = 0.08) and multiple sites of recurrence (p = 0.05) tended to have greater numbers of findings on CT scan previously unsuspected. Thus, CT scan is a valuable guide to treating loco-regional recurrent disease. CONCLUSION: Pretreatment diagnostic thoracic CT scan offers essential information that can alter treatment planning and thus optimize treatment strategy for a large proportion of patients with clinically isolated loco-regional recurrent breast carcinoma. In this population of patients we recommend that thoracic CT examination be considered before the initiation of radiation therapy.

Breast Neoplasms↗
PubMed1998

T classification and clivus margin as risk factors for determining locoregional control by radiotherapy of nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to determine risk factors that affect locoregional control of nasopharyngeal carcinoma (NPC) after radiotherapy. Computed tomography (CT) is utilized for radiotherapy planning and for identifying high risk anatomic areas. METHODS: Between April 1990 and December 1993, 40 consecutive patients (1 in Stage I, 3 in Stage II, 5 in Stage III, and 31 in Stage IV) who had locoregional NPC were given definitive radiotherapy at the Koo Foundation Sun Yat-Sen Cancer Center in Taipei, Taiwan. All patients had individualized CT treatment planning. The dimension of each tumor as shown on the treatment planning CT were mapped on conventional simulation films. The extent of each tumor was further affirmed by magnetic resonance imaging (MRI) and the tumor map revised as necessary. The primary radiation fields were designed to include the primary tumor and potential spread areas with appropriate margins. Concurrent chemotherapy was also given to 35 patients (87.5%) who had positive cervical lymph nodes or primary tumors extending beyond the nasopharynx. RESULTS: By the end of December 1995, after a median follow-up of 42 months and minimal follow-up of 24 months, the locoregional control rate at 4 years was 84.8% (95% confidence interval [CI], 72.3-97.3), disease free survival 68.4% (95% CI, 52. 1-84.7), and overall survival 76.7% (95% CI, 63.4-90.0). The radiation field margin near the sphenoid sinus averaged 1.9 cm, the clivus margin 1.1 cm, the pterygoid fossa margin 2.0 cm, and the oral cavity margin 1.7 cm. Risk factor analysis revealed that T classification and the radiation field margin at the clivus were the most important factors for locoregional control of the tumor. The locoregional control rates were 92.6% (25/27) for T1-T3 patients and 76.9% (10/13) for T4 patients (P = 0.03). The locoregional control rates were 71.4% (5/7) for patients with a clivus margin < 1 cm and 90.6% (29/32) for patients with a clivus margin > or = 1 cm (P = 0.08). CONCLUSIONS: The excellent locoregional control observed in this series may be attributed to the concurrent chemotherapy and radiotherapy as well as meticulous treatment planning with CT and MRI. The precise delineation of the involved area with the aid of CT, which is taken while the patient is in the position for irradiation, serves to define the necessary safety margin of the radiation field. T classification and clivus margin are the most important factors in determining locoregional control of radiotherapy of NPC. The statistical trend observed in this study indicated that the clivus margin should be adequate to reduce the failure around the clivus, as all local recurrences were observed in this area.

Adult↗
PubMed1998

Aerosolization of cationic lipid:pDNA complexes--in vitro optimization of nebulizer parameters for human clinical studies.

Previously, we have described the optimization of the aerosol delivery of a nonviral gene therapy vector to the lungs of rodents (Eastman et al., 1997b). Although aerosolizing cationic lipid:pDNA complexes into a whole-body exposure chamber resulted in high levels of reporter gene expression in the lungs of BALB/c mice, the conditions employed were not optimal for the delivery of lipid:pDNA complexes to the lungs of human patients. That is, the consumption rate of the material in the nebulizer, and thus the delivery time, were very slow and the aerosol was delivered in a continuous flow. Here we describe in vitro experiments used to develop a cationic lipid:pDNA aerosol with characteristics more suitable for delivery to the lungs of humans, as a necessary prerequisite for conducting a clinical study with human cystic fibrosis patients. Using cascade impactors and all-glass impingers, we have screened several commercially available nebulizers for their ability to deliver intact, respirable, active lipid:pDNA complexes in the shortest time possible, and have identified the Pari LC Jet Plus nebulizer as the optimal nebulizer that meets these criteria. Using this nebulizer in an intermittent mode to mimic breath actuation, consumption rates of approximately 0.6 ml/min of the cationic lipid:pDNA complexes (6 mM cationic lipid:8 mM pDNA) were obtained. The plasmid DNA remained intact and the complexes were shown to maintain activity throughout the nebulization run. Based on measurements of the nebulized dose and the mass median aerodynamic diameter, we calculate a delivered dose of approximately 22 micromol (7.2 mg) of pDNA for each 8 ml of cationic lipid:pDNA complex aerosolized to the lungs of a human patient. This dose should be sufficient to test the clinical efficacy of cationic lipid-mediated gene delivery for the treatment of cystic fibrosis.

Aerosols↗
PubMed1998

Assessment of chemosensitivity in patients with osteogenic sarcoma using the doxorubicin binding assay.

BACKGROUND AND OBJECTIVES: Assessment of chemosensitivity in patients with osteosarcoma may help identify those with resistance to chemotherapy. In this study, we investigated the clinical value of the doxorubicin binding assay in its ability to identify patients with drug resistance. METHODS: We tested tumor tissue samples obtained at biopsy of 24 patients with high-grade osteosarcoma aged 9-61 years (mean 19.2) for sensitivity to doxorubicin, using the doxorubicin binding assay. Tumor excision was performed in these patients after neoadjuvant chemotherapy. Chemotherapy response was judged on the basis of tumor necrosis achieved and was compared with doxorubicin sensitivity in each of these patients. RESULTS: Doxorubicin sensitivity was good in 15 and poor in 9 of 24 patients studied. In patients with good sensitivity (n = 15), 9 (60%) exhibited a good response to chemotherapy while response was poor in 6. In patients with poor sensitivity (n = 9), response to chemotherapy was poor in all 9 (100%) patients and 7 (77.8%) of these patients developed metastatic disease within a mean period of 5.2 months, resulting in two deaths. The results were statistically significant at P = 0.0193. CONCLUSIONS: Doxorubicin binding assay may be useful in identifying patients with inherent resistance to chemotherapy. As the outcome of patients showing resistance to doxorubicin is poor, innovative strategies may need to be developed for this group of patients.

Adolescent↗
PubMed1998

Small cell carcinoma of the uterine cervix with large cell neuroendocrine carcinoma component.

A case of cervical small cell carcinoma (SCC) with large cell neuroendocrine carcinoma (LCNC) differentiation is presented. A 35-year-old Taiwanese woman was diagnosed as having stage IIB bulky SCC confirmed by cervical biopsy and underwent induction combination chemoradiotherapy followed by hysterectomy. The pathology of the cervical tumor after the initial treatment showed the residual tumor to be LCNC instead of SCC. Histochemistry, immunohistochemistry, and electron microscopy demonstrated presence of neuroendocrine differentiation on both the biopsy and the surgical specimens. Following surgical resection a course of adjuvant chemotherapy and a local radiation boost were added. Despite complete local control, she developed brain metastasis 8 months later and vertebral spread soon thereafter. The pathology of the brain tumor showed pure SCC. The patient died 19 months after diagnosis and 13 months after completion of treatment. This case suggests that SCC with LCNC component has a similar clinical course as a pure SCC.

Adult↗
PubMed1998

Disparity of medical care utilization among different health insurance schemes in Taiwan.

Potential excess use of health care services caused by insurance has been a major concern for almost every industrialized county. Moral hazard problems and fee-for-service payment methods are considered to be important factors for higher medical care utilization among those insured. Health care availability is another feature reportedly associated with health care use. Using the data from a National Health Interview Survey in Taiwan in 1990, this study examined differences in medical care utilization by beneficiaries under three major social insurance plans (i.e. Labor Insurance-LI, Government Employees' Insurance-GEI, and Farmers' Insurance-FI) which covered about half the population at that time. Logistic and Poisson regression models were applied to examine the effects of relevant factors on the probability and volume of physician visits. Results from the analyses revealed that (1) persons with different insurance plans had a similar higher probability of seeing a doctor than the uninsured, with the odds ratios ranged from 1.8 to 2.0. Also (2) the LI/FI participants consumed 60 73% more physician services than the uninsured, while the GEI enrollees utilized only 30% more physician services. Findings from our study concerning the access and use of physician services in different insurance plans provide some useful information for reforming a health care delivery system.

Health Benefit Plans, Employee↗
PubMed1998

The benefit and risk of postmastectomy radiation therapy in patients with high-risk breast cancer.

To evaluate the efficacy of postmastectomy radiation therapy (PMRT) for prophylaxis against locoregional recurrence in high-risk breast cancer patients, and the rate of complication associated with such treatment, we retrospectively reviewed 79 breast cancers in 78 patients, who were given therapy (PMRT) between April 1990 and March 1995. Radiation doses were 46-50 Gy in 2-Gy fractions. High-risk factors included primary tumor (> or = 5 cm) in 19 (24.1%) patients, positive axillary lymph nodes (> or = 4) in 56 (70.9%) patients, positive or close (< or = 2 mm) surgical margins in 14 (17.7%) patients, and central or inner quadrant tumor with positive axillary nodes and lymphovascular invasion in seven (8.9%) patients. Adjuvant chemotherapy was also given to 69 of 78 (88.5%), patients and hormonal therapy to 41 of 78 (53.7%) patients. The median follow-up time was 25 months (range, 7-66 months) after mastectomy. Our study revealed that locoregional failure as the first site of failure occurred in only one of 78 (1.3%) patients. Relapse-free survival at 3 years was 67.7% [95% confidence interval (CI), 52.0-81.3], and overall survival was 76.9% (95% CI, 63.3-90.6). The incidence of radiological evidence of lung fibrosis increased significantly in patients whose internal mammary chain was included in the radiation field. The occurrence of lung fibrosis can be reduced by changing radiation treatment technique and keeping central lung distance (CLD) of tangential field to < or = 2.8 cm in tangential field technique or < or = 1.4 cm in tangential with a separate internal mammary field technique. We concluded that the risk of locoregional recurrence in high-risk breast cancer patients can be much reduced by PMRT. With careful selection of radiation treatment fields, radiotherapy technique, and limitation of CLD to < or = 2.8 cm in tangential technique or < or = 1.4 cm in separate technique, the risk of symptomatic radiation pneumonitis is minimal. PMRT should be recommended for breast cancer patients who are at high risk for locoregional recurrence.

Adult↗
PubMed1998

Effects of short- and long-term elevated CO2 on the expression of ribulose-1,5-bisphosphate carboxylase/oxygenase genes and carbohydrate accumulation in leaves of Arabidopsis thaliana (L.) Heynh.

To investigate the proposed molecular characteristics of sugar-mediated repression of photosynthetic genes during plant acclimation to elevated CO2, we examined the relationship between the accumulation and metabolism of nonstructural carbohydrates and changes in ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) gene expression in leaves of Arabidopsis thaliana exposed to elevated CO2. Long-term growth of Arabidopsis at high CO2 (1000 microL L-1) resulted in a 2-fold increase in nonstructural carbohydrates, a large decrease in the expression of Rubisco protein and in the transcript of rbcL, the gene encoding the large subunit of Rubisco (approximately 35-40%), and an even greater decline in mRNA of rbcS, the gene encoding the small subunit (approximately 60%). This differential response of protein and mRNAs suggests that transcriptional/posttranscriptional processes and protein turnover may determine the final amount of leaf Rubisco protein at high CO2. Analysis of mRNA levels of individual rbcS genes indicated that reduction in total rbcS transcripts was caused by decreased expression of all four rbcS genes. Short-term transfer of Arabidopsis plants grown at ambient CO2 to high CO2 resulted in a decrease in total rbcS mRNA by d 6, whereas Rubisco content and rbcL mRNA decreased by d 9. Transfer to high CO2 reduced the maximum expression level of the primary rbcS genes (1A and, particularly, 3B) by limiting their normal pattern of accumulation through the night period. The decreased nighttime levels of rbcS mRNA were associated with a nocturnal increase in leaf hexoses. We suggest that prolonged nighttime hexose metabolism resulting from exposure to elevated CO2 affects rbcS transcript accumulation and, ultimately, the level of Rubisco protein.

Arabidopsis↗
PubMed1998

Partial restoration of cAMP-stimulated CFTR chloride channel activity in DeltaF508 cells by deoxyspergualin.

Deletion of the codon encoding phenylalanine 508 (DeltaF508) is the most common mutation in cystic fibrosis (CF) and results in a trafficking defect. Mutant DeltaF508-CF transmembrane conductance regulator (CFTR) protein retains functional activity, but the nascent protein is recognized as abnormal and, in consequence, is retained in the endoplasmic reticulum (ER) and degraded. It has been proposed that this retention in the ER is mediated, at least in part, by the cellular chaperones heat shock protein (HSP) 70 and calnexin. We have investigated the ability of deoxyspergualin (DSG), a compound known to compete effectively for binding with HSP70 and HSP90, to promote trafficking of DeltaF508-CFTR to the cell membrane. We show that DSG treatment of immortalized human CF epithelial cells (DeltaF508) and cells expressing recombinant DeltaF508-CFTR partially restored cAMP-stimulated CFTR Cl- channel activity at the plasma membrane. Although there are several possible explanations for these results, one simple interpretation is that DSG may have altered the interaction between DeltaF508-CFTR and its associated chaperones. If this is correct, agents capable of altering the normal functioning of cellular chaperones may provide yet another means of restoring CFTR Cl- channel activity to CF subjects harboring this class of mutations.

1-Methyl-3-isobutylxanthine↗