Biomedical subjects

T H Chen

Publications and source records attributed to T H Chen.

At least 55 records · Page 3Linked to original sources

PubMed2000

Effect of amino acid mixtures on nasal allergic responses induced by toluene diisocyanate in mice.

We studied the effect of various amino acid mixtures on nasal allergy induced by the intranasal application of toluene diisocyanate (TDI) in mice. In Experiment 1 (Exp. 1), mice were fed a 25% casein, soy protein isolate (SPI), egg white protein (EW) or gluten diet. In Experiment 2 (Exp. 2), mice were fed a 25% amino acid mixture diets patterned after casein (AA-casein), SPI (AA-SPI), EW protein (AA-EW) or gluten (AA-gluten). In Experiment 3 3 (Exp. 3) we modified the glutamine/glutamic acid (Gln/Glu) concentrations in the amino acid mixtures. Mice were fed a 25% AA-SPI, low Gln/Glu AA-SPI (LG-AA-SPI), AA-EW or high Gln/Glu AA-EW (HG-AA-EW) diet. At the 5th week, mice were divided into sensitized (sen-) and non-sensitized (ns-) groups. The mice in sensitized groups were treated with two courses of intranasal application of toluene diisocyanate (TDI) in ethyl acetate for 5 consecutive days, separated by 9 days rest. The non-sensitized groups of mice were treated with a vehicle. Nine days after the second sensitization, all mice were provoked by TDI. Nasal responses and serum IgE concentration were studied. The findings of Exp. 1 showed that the sen-EW group exhibited a lower body weight gain, higher nasal symptom score and higher IgE concentration than the other sensitized groups. The findings dings of Exp. 2 showed that the sen-EW group had a lower body weight gain, higher nasal symptom score and higher IgE concentration than the other sensitized groups. In Exp. 3, the AA-EW group showed a higher total nasal score and IgE concentration than the HG-AA-EW group, however, the findings of LG-AA-SPI and AA-SPI were similar. These findings demonstrated that amino acid mixtures affect nasal allergy induced by the intranasal application of TDI in mice.

Administration, Intranasal↗

PubMed2000

[Quantitative assay of telomerase activity in head and neck squamous cell carcinoma].

OBJECTIVE: To detect and quantify telomerase activity in tissues from head and neck squamous cell carcinoma (HNSCC), and to explore whether the levels of telomerase activity can be a useful marker for cancer risk assessment in HNSCC. METHOD: The levels of telomerase activity of 55 fresh specimens obtained from 25 patients with HNSCC were detected by the method of telomeric repeat scintillation radioactive count, including 25 primary tumors, 7 samples of neck metastases and 23 corresponding normal tissues as control. In 7 patients, both primary and metastatic tumors were obtained. The levels of telomerase activity were determined with a liquid scintillation counter. The basic principle of the technique is that a G-rich oligonucleotide strand of telomeric sequence is used as primer, 3H-dTTPs are incorporated into the products while telomerase elongates the primers, and then free 3H-dTTPs are removed by rinsing step, finally radioactive count per minute (cpm) of products is detected, and the levels telomerase activity can be evaluated according to the value (cpm). RESULT: 1. The levels of telomerase activity (cpm) in tissues with HNSCC were significantly higher than those in the normal tissues (P < 0.05); 2. The levels of telomerase activity in the primary tumors were higher than those of their neck metastases, but the difference was not statistical significance (P > 0.05); 3. The levels of telomerase activity in the neck metastases were remarkably higher than those in the normal tissues (P < 0.05). CONCLUSION: 1. Detection of telomerase activity in HNSCCs can be a useful marker for cancer assessment. 2. To quantify telomerase activity may have clinical diagnostic value for HNSCC. 3. The levels of telomerase activity in the metastatic lymph nodes were higher.

Carcinoma, Squamous Cell↗

PubMed1999

Protein kinase C activation blocks calcium receptor signaling in Xenopus laevis oocytes.

We examined whether calcium receptor (CaR) signaling is affected by protein kinase C (PKC) activation by assessing the effects of phorbol-12-myristate-13-acetate (PMA) on 45Ca2+ efflux from Xenopus laevis oocytes expressing wild-type (WT) and mutant bovine parathyroid CaRs. Raising extracellular [Ca2+] ([Ca2+]0) from 0.5 to 5.5 mM increased 45Ca efflux (26 +/- 3-fold) in oocytes expressing full-length and C-terminally truncated receptor (amino acid 1-895). These increases in 45Ca efflux were blocked by 88 +/- 3% after PMA treatment for 20 min. Three consensus PKC phosphorylation sites (Thr-647, Ser-795, and Thr-889) were mutated in the context of the full-length and truncated CaR. PMA treatment inhibited high [Ca2+]0-induced responses in oocytes expressing the Ser795Ala CaR (1-895), Thr889Ala CaR (1-895), and Ser795Ala/Thr889Ala CaR (1-895) by 30-40% compared with untreated controls (P < 0.05). A triple mutant of the full-length CaR demonstrated similarly reduced susceptibility to inhibition of 45Ca efflux by PMA. Thus, these sites are important in mediating the effects of PKC activation on CaRs, but other residues and effector molecules are likely to participate in the effects of PKC on CaR-induced signal transduction in target cells.

Animals↗

PubMed1999

Evaluation of a selective screening for colorectal carcinoma: the Taiwan Multicenter Cancer Screening (TAMCAS) project.

BACKGROUND: Although the efficacy of mass screening for colorectal carcinoma (CRC) with a fecal occult blood test has been demonstrated in several randomized trials, a mass screening approach used in countries with intermediate or low incidence of CRC might be costly. Screening high risk people may be an alternative approach, to aid in the prevention of death from CRC. However, the efficacy of CRC screening for high risk people in such countries is uncertain. METHODS: For this study, a multicenter design was devised to identify high risk groups without clinical symptoms related to CRC; these subjects were identified through the study of index cases of CRC in Taiwan. Colonoscopy, in combination with a fecal occult blood test or double-contrast barium enema, was used to screen high risk groups. A total of 8909 subjects were invited to attend screening. Of 8909, 81 with asymptomatic CRC were detected in one-shot screening. Markov models, in conjunction with a simulated approach, were proposed to estimate relevant parameters in relation to disease progression and to assess the effect of the interval between screenings on the efficacy of CRC screening for these high risk groups. RESULTS: The estimated preclinical incidence rate was 0. 00396 (95% confidence interval [CI], 0.002944-0.004985), which was 21 times that reported from a cancer registry in 1994. The simultaneous estimations of mean sojourn time (the average duration between the preclinical screen-detectable phase and the clinical phase) and sensitivity were 2.8 years (95% CI, 2.15-4.30) and 95.0% (95% CI, 24.4-99.9%), respectively. Predictions of mortality reduction for people who received annual, biennial, and triennial screening regimes compared with controls were 26% (95% CI, 0-50%), 23% (95% CI, 0-48%), and 21% (95% CI, 0-47%), respectively. CONCLUSIONS: The efficacy of selective colorectal carcinoma screening has been demonstrated in this study. A high preclinical CRC incidence rate also suggests that such a screening strategy might be cost-effective for countries with intermediate or low incidence of CRC. Methods proposed in this study can be used to evaluate the efficacy of CRC screening in similar screening trials.

Colonoscopy↗

PubMed1999

An in vitro comparison of the motion behavior of different bipolar endoprostheses.

The relative motion of 3 different bipolar endoprostheses was evaluated in vitro. A paired fresh acetabulum was frozen at 0 degrees C and defrosted 12 hours before the experiment. Three bipolar endoprostheses were evaluated: UNIQHIP system (United Orthopedics), UHR system (Osteonics), and AML system (Depuy). The surface roughness and spherical roundness of outer shells and inner heads of the bipolar prostheses were measured before the experiments. The acetabulum and outer shell of the bipolar prostheses were fixed on a Bionix 858 material testing system axially by separate fixation tools. The axial load of 1,400 N and 2,800 N was than applied on the specimen. The axis was rotated from 0 degrees to 90 degrees at the speed of 1 degree/s. All 3 outer shells were tested to this paired acetabulum randomly and separately. The frictional torque on the outer bearing surface of the different prostheses was recorded by the material testing system. The frictional torque on the inner bearing surface was also measured by the same procedure as was done for the outer bearing. The final results were statistically compared by the 1-way analysis of variance test method. Bipolar prostheses of the UHR system showed the largest frictional torque on outer bearing when it was loaded with 1,400 N and 2,800 N. The final results showed that all the bipolar prostheses had ideal motion behavior when functioning under the loading of 1,400 N. The frictional torque on the inner bearing was found to be larger than the frictional torque on the outer bearing in some prostheses when the loading was increased to 2,800 N. Thus, the bipolar endoprostheses functioned as unipolar prostheses. The only relative motion remained between the outer bearing surface and the acetabulum. This effect causes complications, such as implant protrusion in the acetabulum.

Hip Prosthesis↗

PubMed1999

Enhanced tolerance to light stress of transgenic Arabidopsis plants that express the codA gene for a bacterial choline oxidase.

Arabidopsis thaliana was transformed with the codA gene from Arthrobacter globiformis. This gene encodes choline oxidase, an enzyme that converts choline to glycinebetaine. The photosynthetic activity, monitored in terms of chlorophyll fluorescence, of transformed plants was more tolerant to light stress than that of wild-type plants. This enhanced tolerance to light stress was caused by acceleration of the recovery of the photosystem II (PS II) complex from the photo-inactivated state. The transformed plants synthesized glycinebetaine, but no changes were detected in the relative levels of membrane lipids or in the relative levels of fatty acids in the various membrane lipids. Transformation with the codA gene increased levels of H2O2, a by-product of the reaction catalyzed by choline oxidase, by only 50% to 100% under stress or non-stress conditions. The activity of ascorbate peroxidase and, to a lesser extent, that of catalase in transformed plants were significantly higher than in the wild-type plants. These observations suggest that H2O2 produced by choline oxidase in the transformed plants might have stimulated the expression of H2O2 scavenging enzymes, with resultant maintenance of the level of H2O2 within a certain limited range. It appears that glycinebetaine produced in vivo, but not changes in membrane lipids or in the level of H2O2, protected the PS II complex in transformed plants from damage due to light stress.

Adaptation, Physiological↗

PubMed1999

Anaerobic treatment of poultry mortalities in a modified LB-UASB system.

The efficiency of a modified LB-UASB system in treating poultry mortalities was tested. The anaerobic digestion system consisted of an upflow anaerobic sludge blanket (UASB) and three leachbeds (LB). The LBs were batch-loaded with mortality to be treated. The LBs were sequentially connected to the UASB, one at a time. Leachate from a connected LB was fed to the UASB while effluent from the UASB overflowed to the LB to form a closed loop. When the concentrations of leachate from the first LB became so low that it could no longer support accelerated methanogenesis in the UASB, it was replaced by a second LB containing a new batch of mortality. Concentrated leachate from the second LB allowed the UASB to continue operation at higher loading rates (LR), thus, alleviating the problems of lengthy LR build-up and idling time. Meanwhile, the off-lined LB continued to mature independently. The UASB was connected to a third LB when the second LB entered accelerated methanogenesis phase. Operation of the first LB was stopped when CH4 production rate from it became marginal. The remaining solids material was replaced by a new batch of mortality to start the second cycle. The first cycle was completed when fermentation in the third LB was ended. The modified LB-UASB system performed significantly better than the original system. It took an average of only 86 days to treat one batch of mortality, yet, the methane yield was about 40% higher. The average methane yield was 0.28 m3 (kg wet weight)-1. Strategies to optimize system performances are discussed.

Anaerobiosis↗

PubMed1999

A Markov chain model to assess the efficacy of screening for non-insulin dependent diabetes mellitus (NIDDM).

BACKGROUND: The high prevalence and severe consequences of non-insulin dependent diabetes mellitus (NIDDM) in Taiwan calls for urgent measures to detect this disease in the asymptomatic phase. However, the efficacy of early detection of NIDDM is highly dependent on its natural history from the disease-free state, through the asymptomatic to the symptomatic phase and death from NIDDM or other causes. METHODS: In order to project the above progression, a five-state illness-and-death Markov chain model was proposed to estimate these transition parameters using data from two rounds of a blood sugar screening programme for NIDDM in Puli, in central Taiwan. RESULTS: Results showed that the annual incidence for asymptomatic NIDDM was 10.67 per 1000 (95% CI: 8.26-13.79) and the average duration between the asymptomatic and symptomatic phases (the sojourn time) was 8 years (95%CI: 5.74-11.29). The 10-year survival rate for asymptomatic NIDDM (79.35%) was better than that for symptomatic NIDDM (69.45%). Prediction of deaths from NIDDM was performed to assess how the efficacy of screening for NIDDM varied by different screening frequencies (annual, biennial, 4-yearly and the control group). Results indicated there is no substantial difference in mortality reduction from NIDDM among the annual, biennial and 4-yearly screening regimens. However, a 4-yearly screening regimen significantly reduced deaths from NIDDM by 40% (95% CI: 26-51%). CONCLUSIONS: A long sojourn time and the substantial reduction in mortality suggest that a 4-yearly screening regime for NIDDM would be most effective and feasible in Taiwan. The proposed five-state Markov chain model can be applied to other similar NIDDM screening projects.

Adolescent↗

PubMed1999

Distribution of the superficial temporal artery in the Chinese adult.

The superficial temporal artery is important in head and neck surgery. Ethnologic variation may affect surgical procedure. In this study, we evaluated the variations of the artery in Chinese adults. We measured its bifurcating location, the diameter of its vessels, and its relationship to nearby structures. A total of 26 cadavers with 52 superficial temporal arteries were examined in 3 consecutive years. The superficial temporal artery ran 1.14 cm anteriorly to the bony external auditory canal. The average diameters of the superficial temporal artery, frontal branch, and parietal branch were 2.14, 1.61, and 1.68 mm, respectively. In 45 of 52 cases (86.5 percent), bifurcation of the artery occurred well above the zygomatic arch. The present study thus demonstrated that the superficial temporal artery in the Chinese adult differs from that in the Caucasian and has provided a detailed anatomic distribution analysis of the superficial temporal artery in Chinese adults, which should benefit the clinician in dealing with operation procedures related to this artery.

Adult↗

PubMed1999

Expression and signal transduction of calcium-sensing receptors in cartilage and bone.

We previously showed that Ca2+-sensing receptors (CaRs) are expressed in chondrogenic RCJ3.1C5.18 (C5.18) cells and that changes in extracellular [Ca2+]([Ca2+]o) modulate nodule formation and chondrogenic gene expression. In the present study, we detected expression of CaRs in mouse, rat, and bovine cartilage and bone by in situ hybridization, immunocytochemistry, immunoblotting, and RT-PCR; and we tested the effects of CaR agonists on signal transduction in chondrogenic and osteogenic cell lines. In situ hybridization detected CaR transcripts in most articular chondrocytes and in the hypertrophic chondrocytes of the epiphyseal growth plate. Expression of CaR transcripts was weak or absent, however, in proliferating and maturing chondrocytes in the growth plate. In bone, CaR transcripts were present in osteoblasts, osteocytes, and bone marrow cells, but rarely in osteoclasts. A complementary DNA was amplified from mouse growth plate cartilage, which was highly homologous to the human parathyroid CaR sequence. Immunocytochemistry of cartilage and bone with CaR antisera confirmed these findings. Western blotting revealed specific bands (approximately 140-190 kDa) in membrane fractions isolated from growth plate cartilage, primary cultures of rat chondrocytes, and several osteogenic cell lines (SaOS-2, UMR-106, ROS 17/2.8, and MC3T3-E1). InsP responses to high [Ca2+]o were evident in C5.18 cells and all osteogenic cell lines tested except for SaOS-2 cells. In the latter, high [Ca2+]o reduced PTH-induced cAMP formation. Raising [Ca2+]o also increased intracellular free [Ca2+] in SaOS-2 and C5.18 cells. These studies confirm expression of CaRs in cartilage and bone and support the concept that changes in [Ca2+]o may couple to signaling pathways important in skeletal metabolism.

Animals↗

PubMed1999

Treatment of large skeletal defects in the lower extremities using double-strut, free vascularized fibular bone grafting.

This article reports on the use of double-strut, free vascularized fibular grafts to treat six patients with infected nonunion or traumatic bone loss in the femur or tibia after prolonged treatment and multiple operations. The defects were 6-13 cm long. Five patients achieved solid union within 6 months, and one patient required additional cancellous grafting to achieve union at the distal end of the fibula. One patient experienced a stress fracture due to strenuous exercise, and union was achieved 3 months after reapplying an external fixator. Although three patients had some restricted knee motion, all patients had a satisfactory outcome in regard to walking, and no limb-length discrepancies were noted in any patient.

Adult↗

PubMed1999

Vascularized iliac bone graft for displaced femoral neck fractures in young adults.

From November 1989 to September 1994, a total of 26 patients (18 men and 8 women) with acute displaced femoral neck fractures were treated with closed reduction and Knowles pinning combined with vascularized iliac bone grafting. Mean patient age was 37.5 years (range: 24-48 years). The mean time interval from injury to surgery was 3.6 days (range: 1-10 days). One patient experienced loss of the reduction at 6 weeks postoperatively and subsequently went on to hip replacement. Mean follow-up for the remaining 25 patients was 56.2 months (range: 20-78 months). All fractures united within 4 months. The average union time was 3.3 months. Plain radiographs confirmed the presence of avascular necrosis in 2 patients during the final follow-up; 1 of these patients developed systemic lupus erythematous 1 year after the fracture and had been treated with high doses of corticosteroid. Functional and radiographic results were satisfactory in the remaining patients.

Adult↗

PubMed1998

Efficacy of breast-cancer screening for female relatives of breast-cancer-index cases: Taiwan multicentre cancer screening (TAMCAS).

Although the efficacy of mass screening for breast cancer has been established in Western countries, this strategy may be too costly for other countries with low incidence rates of breast cancer. We propose an alternative approach to screen female relatives of breast-cancer-index cases from hospitals, as part of the Taiwan multicentre cancer screening (TAMCAS) project. In order to assess the efficacy of this programme, and to estimate how often this high-risk group should be screened, we firstly elucidated the disease natural history from the pre-clinical screen-detectable phase (PCDP) by estimating the relevant parameters based on Markov chain models. We further predicted the proportion of interval cancers, advanced breast tumours and deaths from breast cancers by different screening frequencies. Results showed that the estimate of mean sojourn time (MST) for this high-risk group (1.9 years; 95% CI.1.18-4.86) is shorter than that for females from the general population. Analysis of a surrogate endpoint based on regional lymph-node spread and tumour size shows that annual screening for this high-risk group is likely to confer a significant 33% reduction in breast-cancer mortality compared with a non-significant 25 and 20% reduction for 2 yearly and 3-yearly screening regimes respectively. The above results suggest that a 1-year interval might be appropriate for this high-risk group. A simple cost-effectiveness analysis indicates a cost per year of life saved for mass screening ($72,480) 15 times that for the high-risk group ($4,851 ).

Breast Neoplasms↗

PubMed1998

Partial or complete circular duodenectomy with highly selective vagotomy for severe obstructing duodenal ulcer disease: an initial experience.

OBJECTIVE: To evaluate partial and complete circular duodenectomy combined with highly selective vagotomy (HSV) for relief of gastric retention. DESIGN: A retrospective, case-comparison study. SETTING: University hospital referral center. PATIENTS: Eighteen patients with severe obstructing duodenal ulcer disease defined by failure of a saline load test and endoscopic narrowing of the gastric outlet to 5 mm or less. METHODS: In patients with severe obstructing ulcer the diseased duodenal segment was excised with electrocautery (partial excision, 10 patients; complete excision, 8 patients). An HSV was then done. Postoperative fasting gastric residuum measurement and measurement of the emptying of liquids and solids was done at 3 months and patients were weighed at 3 and 12 months. RESULTS: No patient experienced postoperative gastric retention or required reoperation in a 2-year follow up. The early emptying of liquid (20 minutes) in complete circular duodenectomy plus HSV was more rapid than in normal subjects and duodenal ulcer patients. The emptying of solids was slightly delayed in partial duodenectomy plus HSV compared with duodenal ulcer patients but not with normal controls. The emptying of solids in duodenal ulcer patients was more rapid than in normal controls. Weight gain was excellent at 3 and 12 months. CONCLUSION: Partial duodenectomy and complete circular duodenectomy plus HSV are more efficacious than alternative nonresective procedures in restoring gastric emptying to near normal and restoring weight in patients with obstructing duodenal ulcer.

Duodenal Obstruction↗

PubMed1998

Effect of antioxidant in endothelial cells exposed to oxidized low-density lipoproteins.

Antioxidants such as probucol and alpha-tocopherol have been shown to attenuate the oxidation of low-density lipoproteins (LDL) and atherosclerotic lesions in animal models of atherosclerosis. The purpose of this study is to determine the protection effect of antioxidants on endothelial cells when exposed to oxidized and native LDL. In a cell-free system, we found that probucol, alpha-tocopherol, and ascorbic acid inhibited copper-induced LDL oxidation by a dose-dependent fashion (from 1 microM to 10 mM). In porcine aortic endothelial cells, antioxidants alone did not change basal endothelin-1 (ET-1) secretion. When porcine aortic endothelial cells were exposed to LDL and oxidized-LDL, both of them stimulated ET-1 secretion dose-dependently, whereas oxidized-LDL elicited higher ET-1 secretion. However, probucol, alpha-tocopherol, and ascorbic acid did not prevent LDL or oxidized-LDL induced ET-1 secretion. Furthermore, nimodipine inhibited both of native and oxidized LDL induced ET-1 secretion. Since Ca2+ channel blocker reduced the elevation of induced ET-1 secretion, the [Ca2+]i is possibly involved for the regulation of ET-1 secretion. Our results suggest that antioxidants can only prevent the oxidation of LDL rather than oxidized and native LDL-induced ET-1 secretion in vascular endothelial cells. The increase in the [Ca2+]i of endothelial cells through the opening of voltage-dependent Ca2+ channels may be involved in the LDL-induced ET-1 release.

Animals↗

PubMed1998

Pseudoxanthoma elasticum. Case report.

Pseudoxanthoma elasticum is an uncommon disorder of elastin with characteristic skin laxity. Rhytidectomy of the excessive redundant skin is necessary for cosmetic improvement, and reports of surgical management are rare. We report a case of pseudoxanthoma elasticum with involvement of neck, axillae, breasts, abdomen, thighs, and perineum, together with angioid streaking of fundi. Rhytidectomy of the lax cervical skin was undertaken with satisfactory results after a 13 month follow-up. We have reviewed other published reports to obtain a better understanding of the genetics, histopathology, vascular and ophthalmological manifestations, and also the surgical implications of pseudoxanthoma elasticum.

Adult↗

PubMed1998

Performances of mesophilic anaerobic digestion systems treating poultry mortalities.

A closed-loop anaerobic digestion system consisting of a leachbed (LB) and an upflow anaerobic sludge blanket (UASB) was tested as an alternative for the disposal of poultry mortalities. This paper compares the performances of three LB-UASB treatment systems with different initial moisture contents in the LBs. Each LB was loaded with one chicken and 5, 10 or 18 liters of water. The LBs initially carried out he hydrolysis/acidification phase while the UASBs the methanogenesis phase. Due to repeated inoculation by the UASBs, the LBs with 10 and 18 liters of water started producing methane on day 5, while the one with 5 liters of water on day 19. However, methane production rates were low before day 40 for the LB with 10 liters of water and day 60 for the other LBs. Methane production gradually improved as the LBs continued to receive ungranulated sludge from the UASBs. The LBs eventually became balanced methane reactors. Continued balanced fermentation in the LBs resulted in leachates with very low substrate concentrations that could no longer support high-rate methanogenesis in the UASBs. Consequently, methane production rates from the UASBs decreased quickly while that from the LBs reached peak levels. Cumulative methane production from each LB eventually exceeded that from its connecting UASB. After 118 days of digestion, 414, 437 and 470 liters of methane were produced from the three systems, respectively. Cumulative methane production from the LBs with 5 and 18 liters of water accounted for 63% of the total methane produced from their respective systems. The LB with 10 liters of water produced 75% of the total methane from that system. Methane yields ranged from 0.485 to 0.554 m3 (Kg TS)-1. About 86% of the initial dry weight was biodegraded. All three systems performed very well with little operational problems. Overall, the systems that started with 10 liters of water in the LB performed the best. Strategy for enhancing system performances and implementing farm applications are discussed.

Anaerobiosis↗

PubMed1998

Regulation of extracellular calcium-activated cation currents by cAMP in parathyroid cells.

Parathyroid cells express Ca2+-sensing receptors that couple changes in the extracellular Ca2+ concentration ([Ca2+]o) to increases in the intracellular free Ca2+ concentration ([Ca2+]i) and to the suppression of parathyroid hormone secretion. Using whole cell patch clamping, we previously identified voltage-independent Ca2+-conducting currents in bovine parathyroid cells that increased with rising [Ca2+]o and were blocked by Cd2+ and nifedipine. Because cAMP-dependent phosphorylation regulates dihydropyridine-sensitive Ca2+ channels in other systems, we tested whether cAMP modulates these currents. At 0.7 mM Ca2+, nonselective Ca2+-conducting currents were suppressed by 30-50% when the recording pipette was perfused with cAMP. High-[Ca2+]o-induced increases in membrane currents were also abrogated. The effects of cAMP were reversible and dose dependent (3 x 10(-9) to 3 x 10(-3) M) and required ATP in the pipette solution. Perfusion of the cell interior with the catalytic subunit of protein kinase A mimicked the effects of cAMP, as did perfusion of the bath with the adenylate cyclase activator forskolin. These findings support the idea that cAMP-dependent phosphorylation suppresses high-[Ca2+]o-induced cation currents and may play a role in regulating ion fluxes in parathyroid cells.

Animals↗