Biomedical subjects

C C Chen

Publications and source records attributed to C C Chen.

At least 307 records · Page 17Linked to original sources

PubMed1997

Manifestations and surgical treatment of choledochal cyst in different age group patients.

Whether early surgery is necessary for asymptomatic choledochal cyst is still controversial. In order to evaluate the manifestations of choledochal cyst on different age group patients, we investigated 57 patients, 36 females and 21 males, who underwent surgery for choledochal cyst at National Taiwan University Hospital from July 1988 to June 1995. Of these, 93% were classified as type I according to the Alonzo-Lej or Todani classification method. Patients were divided into three groups according to their age at surgery: group I, 14 infants (< 1-yr); group II, 28 children (1-16 yr); and group III, 15 adults (> 16 yr). The most common symptom in infants was jaundice, while abdominal pain was the most frequent in children and adults. Preoperative evaluation of liver function showed that alanine aminotransferase was higher in group II (160 +/- 77 IU/L) and group III (164 +/- 75 IU/L) than group I (74 +/- 28 IU/L). A higher tendency of biliary sludge and stone formation was noticed in group III (6/15, 40%) when compared with group I (2/14, 14.3%) and group II (5/28, 17.9%). The incidence of high bile amylase concentration in the choledochal cyst was higher in groups II (16/21,76.2%) and III (9/11, 81.8%) than in group I (2/9, 22.2%). There was more inflammatory changes detected in the choledochal cyst wall and gall bladder by histologic examination in older patients (groups II and III). Therefore, an early surgery for choledochal cyst is suggested for prevention of liver injury, biliary sludge, stone formation and pancreatitis.

Adolescent↗

PubMed1997

Liposomes-coated hydroxyapatite and tricalcium phosphate implanted in the mandibular bony defect of miniature swine.

Hydroxyapatite and tricalcium phosphate have been used as bone implants for some period of time. Now unfortunately, these materials have failed to become the nucleation sites for bone regeneration. We hypothesized that coating hydroxyapatite and tricalcium phosphate with negatively charged liposomes may improve the nucleation process for new bone formation. The present study was designed to test this hypothesis. Experiments were carried out in 15 miniature swines' mandibular angle with artificial bony defects. In each of the swine, the bony defects on one side were implanted with either liposomes coated with hydroxyapatite or liposomes coated with tricalcium phosphate, while the other side served as control. At the end of the third and sixth weeks following the operation, we observed result, took histology and radiographs of the operated area. The results showed that liposomes-coated materials were biocompatible and their clinical endpoint was enhanced. At the end of the third week, the implant material was surrounded by dense connective tissues. At the end of the sixth week, there were new bone formations near the implanted material. In addition, liposomes which were immobilized in agarose gel and implanted in the defects showed new bony bridge formation. These observations suggest that liposomes have the ability in promoting repair of osseous deficiencies.

Alveolar Process↗

PubMed1997

The psychiatric manifestation of Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is considered to be very rare in the population, and the psychiatric manifestation of the disease even rarer with only one report in the past few years in Taiwan. To clarify whether the psychiatric manifestation of CJD is really rare or whether it is neglected in Taiwan, the authors reviewed the discharge notes of patients who had been admitted to a neurological unit in the past 15 years and conducted a chart review of the patients of CJD supported by the clinical courses, EEG finding and brain biopsies. An inquiry was made by telephoning their families to follow up their condition after discharge. Five of the 8 cases with CJD had psychiatric symptoms including changes of mood, thought, behavior and perception during their course of illness. Four cases had been sent to the psychiatric unit and received treatment under several kinds of psychiatric diagnoses. Two patients had been admitted to the psychiatric unit and one had received electroconvulsive treatment. Two of the patients had been suspected to be the victims of neuroleptic malignant syndrome. It is likely that it is psychiatrists who will meet CJD patients first in the early stages of disease. CJD should be kept in mind and EEGs with detailed neurological checkups should be completed, if the cognitive functions of the patients with unusual neurological symptoms deteriorate quickly and their psychiatric symptoms fail to respond to any treatment.

Aged↗

PubMed1997

Comparison of parathyroid imaging with technetium-99m-pertechnetate/sestamibi subtraction, double-phase technetium-99m-sestamibi and technetium-99m-sestamibi SPECT.

UNLABELLED: The ability of 99mTc-pertechnetate/sestamibi subtraction, double-phase 99mTc-sestamibi and 99mTc-sestamibi SPECT imaging to localize abnormal parathyroid tissue was compared. METHODS: Fifty-five consecutive patients had parathyroid imaging before surgery for hyperparathyroidism. Imaging consisted of 99mTc-pertechnetate pinhole images of the neck followed by 99mTc-sestamibi pinhole images of the neck and parallel-hole images of the neck and chest (early images). Within 2.5-4.0 hr later pinhole images of the neck, parallel-hole and SPECT images of the neck and chest were obtained (late images). Nodular foci of increased sestamibi activity were considered abnormal. RESULTS: The sensitivity for abnormal parathyroid glands by visual comparison of early images and pertechnetate images was 72%-75%, late images and pertechnetate images was 73%-78% and double-phase (early and late) sestamibi images was 62%-65%; computer subtraction of pertechnetate from early images was 71%-74%; and SPECT imaging was 79%. The sensitivity for parathyroid adenomas was 89%-98%, while the sensitivity for hyperplastic parathyroid glands was only 47%-58%. CONCLUSION: Late imaging, computer subtraction and SPECT may not be necessary since they provided only marginal improvements on visual comparison of early sestamibi with pertechnetate images. Double-phase sestamibi imaging was less sensitive, so baseline thyroid imaging with pertechnetate is recommended.

Adenoma↗

PubMed1997

Quantification of left ventricular function with thallium-201 and technetium-99m-sestamibi myocardial gated SPECT.

UNLABELLED: Myocardial gated SPECT with 99mTc-sestamibi has been used to quantify left ventricular function. The purpose of this study was to determine if myocardial gated SPECT with 201Tl was possible and reliable to quantify left ventricular function. METHODS: One hundred and four patients referred for a myocardial perfusion study were included. Myocardial gated SPECT acquisition was performed 15 min after the intravenous injection of 111 MBq (3mCi) 201Tl and at 1 hr postinjection of 925 MBq (25 mCi) 99mTc-sestamibi. A commercially available automated myocardial gated SPECT processing software was used. Parameters evaluated were left ventricular ejection fractions (LVEF), end-diastolic volumes (EDV), end-systolic volumes (ESV) and stroke volumes (SV). RESULTS: The correlation between gated SPECT with 201Tl and gated SPECT with 99mTc-sestamibi was: r = 0.93 for LVEF, 0.92 for EDV, 0.96 for ESV and 0.68 for SV. CONCLUSION: Myocardial gated SPECT quantification of left ventricular function with 201Tl was possible and as reliable as gated SPECT with 99mTc-sestamibi. There was excellent correlation between gated SPECT with 201Tl and gated SPECT with 99mTc-sestamibi. In addition to assessment of myocardial perfusion, myocardial function and viability can be quantified in a single gated 201Tl study.

Coronary Disease↗

PubMed1997

[Multiple myeloma with oral manifestations--report of two cases].

Multiple myeloma is a neoplastic disorder of bone that originates from cells of bone marrow. It is most commonly seen within the age range of 50-80 years, cases under the age of 40 being rare. Men are affected more frequently than are women. Bone pain is the cardinal clinical symptom in multiple myeloma. Because of the destruction of bone, pathologic fracture is fairly common. In the oral manifestations, the mandible is involved far more frequently than the maxilla, especially the most active hematopoietic areas-the remus, angle and molar region of the mandible. Other signs and symptoms of jaw involvement include swelling, pain, and increased tooth mobility. Extraosseous lesions may result in paresthesia of soft tissue and gingival enlargement with bleeding tendency. Roentgenographic examination will usually reveal numerous punched-out lesions in a variety of bones. In addition, blood examination will reveal hyperglobulinemia and Bence-Jones protein may be present in the urine of myeloma patients. The histological features of myeloma are closely packed cells resembling plasma cells. Case 1 in this report is a 64-year-old female, who has been diagnosed as having multiple myeloma (IgG, lambda). She was referred to our hospital because of gingival swelling, bleeding and pain. Case 2 is a 60-year-old female suffering from spontaneous gingival bleeding. After blood, urine examination and bone marrow biopsy, multiple myeloma was diagnosed (IgG, lambda). This paper reports the clinical manifestations and treatment courses of these two cases, and the concerns of treatment of multiple myeloma are also discussed.

Female↗

PubMed1997

Correlation of interleukin-1 beta, interleukin-6, and periodontitis.

In order to understand the role of IL-1 beta and IL-6 in the periodontal tissue destruction coincident to periodontitis, we assessed the levels of these two mediators in both the gingival tissue and the serum of patients with periodontal disease and of periodontally healthy subjects. In addition, production of IL-6 by six healthy human gingival fibroblast (HGF) strains in response to IL-1 beta was also investigated. The levels of IL-1 beta and IL-6 in gingival tissues and in serum were examined by ELISA. Both mediators were observed to increase in diseased tissues of patients with adult periodontitis, and there was a positively significant relationship between both mediators and clinical assessments of periodontal destruction. Moreover, a significant correlation was also noted between levels of IL-1 beta and IL-6 in gingival tissues of periodontitis patients (r = 0.4334, p < 0.01). However, there was no significant difference in the serum levels of IL-1 beta and IL-6 between periodontitis patients and periodontally healthy controls. In fibroblast cultures, confluent monolayers of HGF were incubated with recombinant human IL-1 beta for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and assayed for IL-6 activity by inducing proliferation in the IL-6-dependent hybridoma cell line 7TD1. A dose-dependent stimulatory effect of IL-1 beta on IL-6 production by HGF was noted, wherein 3 strains exhibited higher IL-6 activity than the other 3. These data indicate that the levels of IL-1 beta and IL-6 in gingival tissues are closely related to the severity of periodontal disease and that the IL-1 beta and IL-6 produced in gingival tissues may not reflect these two mediators levels in serum. Moreover, IL-1 beta responsiveness of HGF in IL-6 production depends on both the concentration of IL-1 beta and cells of individual subjects. Since HGF are present in periodontal lesion, it is possible that IL-6 secretion stimulated by exposure to inflammatory cell products such as IL-1 beta may participate in the destruction of periodontal tissue in periodontitis.

Adult↗

PubMed1997

Leptomeningeal malignant melanoma arising in neurocutaneous melanocytosis: a case report.

A rare case of histology-proved giant congenital melanocytic nevus (GCMN) with symptomatic leptomeningeal melanocytosis is reported. A 26-year-old man had had a large patch of pigmented nevus over his back and left arm since birth. He had begun to have seizures as well as symptoms and signs of increased intracranial pressure about six months before admission. Serial computed tomography of brain showed hydrocephalus, diffuse leptomeningeal enhancement and multiple well-enhanced, rapid-growing nodules on the surface of the cerebellum and left parietal lobe. Magnetic resonance imaging (MRI) revealed T1 shortening of leptomeninges on precontrast T1 weighted imaging. Skin biopsy was done twice and showed intradermal nevus. Biopsy on one of the intracranial nodules revealed malignant melanoma arising in the melanocytosis. He died one year after the onset of neurologic symptoms. For early diagnosis of neurocutaneous melanocytosis, we suggest 1) MRI, and 2) leptomeningeal biopsy in patients with suspected leptomeningeal malignant melanoma.

Adult↗

PubMed1997

Comparison of various methods of detection of different forms of dengue virus type 2 RNA in cultured cells.

In this report, the sensitivity of various methods of detection of dengue virus type 2 (DEN-2) sense, antisense, replicative intermediate (RI) and replicative form (RF) RNAs in infected mosquito Aedes pseudoscutellaris AP-61 and mammalian baby hamster kidney BHK-21 cells is compared. LiCl precipitation was used for separation of viral RF RNA from RI RNA. Our results show that reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis and slot blot hybridisation of LiCl-fractionated RNA were the most sensitive methods of detection of viral RNA and determination of its single-stranded form. Northern blot analysis was the least sensitive method of detection of any form of viral RNA. Using slot blot hybridisation of LiCl-precipitated RNA, viral RI RNA containing de novo synthesised negative strand viral RNA was first detected 30 mins after virus inoculation in both cell lines. This is the earliest time of detection of DEN viral RNA synthesis in host cells so far reported. However, RF RNA could not be detected until 24 hrs post infection (p.i) in AP-61 and 2 days p.i. in BHK-21 cells, respectively. The sequential order of individual forms of viral RNA detected in the infected cells was RI, RF and genomic RNAs. Viral RNA was detected in AP-61 cells always earlier than in BHK-21 cells. Moreover, the level of viral RNA in AP-61 cells was higher than that in BHK-21 cells, suggesting that the virus replicated more actively in AP-61 cells. In conclusion, the LiCl separation of viral RNA followed by slot blot hybridisation was found to be the most sensitive and reliable method of detection of DEN virus RI, RF and genomic RNAs in the infected cells. Moreover, this method can be applied to determine the replication status of any single-stranded RNA virus in the host.

Aedes↗

PubMed1997

Detection of in vivo P-glycoprotein inhibition by PSC 833 using Tc-99m sestamibi.

Tc-99m sestamibi is a substrate of P-glycoprotein (Pgp) that has been proposed for use as a functional imaging agent for the multidrug resistance-1 phenotype. In vitro, retention of sestamibi by cells that overexpress Pgp can be modified by the presence of Pgp antagonists. In a Phase I trial of the Pgp reversal agent PSC 833, we show that the effects of this reversal agent can also be demonstrated in patients. Nine patients with metastatic renal carcinoma were studied three times: at baseline, approximately 1 day after vinblastine infusion, and while on PSC 833. One patient with metastatic adrenocortical cancer was also studied. Time activity curves and areas under the curve (AUCs) were obtained for tumor, liver, lung, and myocardium, and organ:heart AUC ratios were generated. With PSC 833, tumor visualization was enhanced, and statistically significant increases were found in AUC ratios for tumor and liver compared to baseline. For the liver, significant differences were also found between the vinblastine versus PSC 833 scans but not between the baseline versus vinblastine scans. This study demonstrates that sestamibi retention by tumor and liver is altered in the presence of the reversal agent PSC 833, presumably reflecting inhibition of Pgp. Thus, sestamibi may be useful in vivo as a means of monitoring the effects of this and other reversal agents on various tumors and normal tissues that express Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Elimination of the hydrolytic water molecule in a class A beta-lactamase mutant: crystal structure and kinetics.

Two site-directed mutant enzymes of the class A beta-lactamase from Staphylococcus aureus PC1 were produced with the goal of blocking the site that in the native enzyme is occupied by the proposed hydrolytic water molecule. The crystal structures of these two mutant enzymes, N170Q and N170M, have been determined and refined at 2.2 and 2.0 A, respectively. They reveal that the side chain of Gln 170 displaces the water molecule, whereas that of Met170 does not. In both cases, the catalytic rates with benzylpenicillin are reduced by 10(4) compared with the native enzyme. With nitrocefin, the N170Q mutant enzyme exhibits an approximately 800-fold reduced rate compared with the native enzyme and in addition, a fast initial burst with stoichiometry of 1 mol of degraded nitrocefin/mol of enzyme. Stopped-flow kinetic experiments establish that the rate constant of the burst is 250 s-1, a value comparable with the rate of acylation of the native enzyme. Two structurally based mechanisms that explain the kinetic properties of the N170Q beta-lactamase are proposed, both invoking a deacylation-impaired enzyme due to the elimination of the hydrolytic water molecule. The catalytic rate of the N170M mutant enzyme with nitrocefin is reduced by approximately 50-fold compared with the native enzyme, and the slow progressive inhibition that is revealed indicates that the hydrolysis proceeds via a branched pathway mechanism. This is consistent with the structural data that show that the water site is preserved and that Met170 occupies part of the space that is required for substrate binding. The short contacts between the substrate and the enzyme may lead to structure perturbation and inactivation.

Base Sequence↗

PubMed1996

Structure and kinetics of the beta-lactamase mutants S70A and K73H from Staphylococcus aureus PC1.

Two mutant beta-lactamases from Staphylococcus aureus PC1 which probe key catalytic residues have been produced by site-directed mutagenesis. In the S70A enzyme, the nucleophilic group that attacks the beta-lactam carbonyl carbon atom was eliminated. Consequently, the kcat values for hydrolysis of benzylpenicillin and nitrocefin have been reduced by 10(4)-10(5) compared with the wild-type enzyme. The crystal structure of S70A beta-lactamase has been determined at 2.1 A resolution. With the exception of the mutation site, the structure is identical to that of the native enzyme. The residual activity is attributed either to mistranslation that leads to production of wild-type enzyme and/or to remaining features of the active site that stabilize the tetrahedral transition state. Soaking of the crystals with ampicillin or clavulanate, followed by flash-freezing, has been carried out and the structures examined at 2.0 A resolution. For both experiments, the difference electron density maps revealed buildup of density in the active site that presumably corresponds to beta-lactam binding. However, neither electron density is sufficiently clear for defining the atomic details of the bound compounds. The K73H beta-lactamase has been prepared to test the possible role of Lys73 in proton transfer. It exhibits no detectable activity toward benzylpenicillin, and 10(5)-fold reduction of kcat for nitrocefin hydrolysis compared with the wild-type enzyme. No significant recovery of activity has been measured when the pH was varied between 5.0 and 8.0. The crystal structure of K73H beta-lactamase has been determined at 1.9 A resolution. While the overall structure is similar to that of the native enzyme, the electrostatic interactions between His73 and neighboring residues indicate that the imidazole ring is positively charged. In addition, the hydroxyl group of Ser70 adopts a position that is incompatible with nucleophilic attack on substrates. A crystal soaked with ampicillin was flash-frozen, and diffraction data were collected at 2.1 A resolution. The electron density map showed no indication of substrate binding.

Binding Sites↗

PubMed1996

Identification of signal-induced IkappaB-alpha kinases in human endothelial cells.

Activation of the nuclear transcription factor-kappaB is an early event in endothelial activation. NF-kappaB activation is regulated by the inducible phosphorylation and subsequent degradation of the inhibitory subunit IkappaB-alpha. We identified two discrete kinases of approximately 36 and 41 kDa in the cytoplasm of human umbilical vein endothelial cells that specifically bind to and phosphorylate the IkappaB-alpha subunit. IkappaB-alpha kinase activity is transiently elevated following treatment with either tumor necrosis factor alpha, interleukin-1beta, or bacterial lipopolysaccharides and precedes activation of either mitogen-activated kinase or Jun kinase. Furthermore, activation of the IkappaB-alpha kinases precedes both the appearance of hyperphosphorylated IkappaB-alpha and its subsequent degradation, as well as the translocation of NF-kappaB to the nucleus. Deletion mutagenesis of the IkappaB-alpha polypeptide revealed that these kinases bind in or around the ankyrin repeat domains and phosphorylate residues within the C terminus. These kinases, however, were not identical to casein kinase II and displayed a pharmacologic profile distinct from other known kinases. These kinases may represent components of a signal transduction pathway regulating IkappaB-alpha levels in vascular endothelium.

Ankyrins↗

PubMed1996

Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study.

OBJECTIVE: To compare the sensitivity of somatostatin receptor scintigraphy done using [111In-DTPA-DPhe1]octreotide with that of other imaging methods in the localization of gastrinomas in patients with the Zollinger-Ellison syndrome. DESIGN: Prospective study. SETTING: Referral-based clinical research center. PATIENTS: 80 consecutive patients with the Zollinger-Ellison syndrome. INTERVENTIONS: Conventional tumor localization studies (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], selective angiography, and bone scanning) and somatostatin receptor scintigraphy done using [111In-DTPA-DPhe1]octreotide with single-photon emission CT imaging at 4 and 24 hours. Patients with possible liver metastases had biopsies done for confirmation, and 15 patients had exploratory laparotomies done to assess primary tumor localization. RESULTS: Extrahepatic gastrinomas or liver metastases were identified by ultrasonography in 19% of patients, by CT in 38% of patients, by MRI in 45% of patients, by angiography in 40% of patients, and by somatostatin receptor scintigraphy in 70% of patients. Somatostatin receptor scintigraphy was as sensitive as the other tests combined (59%), and when the results of all other tests were added to the somatostatin receptor scintigraphy results, tumors were localized in 75% of patients. Among patients with a possible primary tumor, the results of ultrasonography were positive in 9%, the results of CT were positive in 31%, the results of MRI were positive in 30%, the results of angiography were positive in 28%, and the results of somatostatin receptor scintigraphy were positive in 58%. Somatostatin receptor scintigraphy was as sensitive as all of the other imaging studies combined; when the results of scintigraphy were added to the results of the other studies, possible primary tumors were identified in 68% of patients. In 24 patients who had histologically proven metastatic liver disease, sensitivities for the detection of any metastatic liver lesions were 46% for ultrasonography, 42% for CT, 71% for MRI, 62% for angiography, and 92% for somatostatin receptor scintigraphy. Somatostatin receptor scintigraphy was significantly better than all of the conventional imaging methods in the identification of gastrinomas later found at surgery (P = 0.004), but it still missed 20% of gastrinomas. CONCLUSIONS: Somatostatin receptor scintigraphy is the single most sensitive method for imaging either primary or metastatic liver lesions in patients with the Zollinger-Ellison syndrome. Because of its sensitivity, simplicity, and cost-effectiveness, it should be the first imaging method used in these patients. For patients with negative results on somatostatin receptor scintigraphy, guidelines about the use of other imaging studies are proposed.

Adolescent↗

PubMed1996

Increased protein kinase C isoform gamma in the hippocampus of pentylenetetrazol-induced chemoshocked mouse.

Protein kinase C (PKC) activity, Western blot analysis of PKC alpha, -beta and -gamma, endogenous substrate protein phosphorylation and Western blot analysis of neuromodulin were studied in the cortex, striatum, hippocampus and cerebellum of mouse brain after pentylenetetrazol-induced chemoshock. The PKC isozymes and endogenous substrates in the crude cytosolic and membrane fractions of these four brain regions were partially purified by DE-52 columns eluted with buffer containing 100 or 200 mM KCl. Almost the same PKC activity in the cortex, striatum, hippocampus and cerebellum was found. This kinase activity was increased in the membrane fractions of hippocampus from chemoshocked mice, while that in other brain regions was not changed. On further analysis by immunoblotting, this increased activity was found to be due to the increase of PKC gamma isozyme. The in vitro phosphorylation of neuromodulin was also found to be increased in the hippocampus of chemoshocked mice, while the level of neuromodulin was not changed after chemoshock. Therefore, an increase of PKC gamma alone, but not neuromodulin, in the hippocampus contributed to the increased phosphorylation of this substrate in chemoshocked mice.

Animals↗

PubMed1996

Swiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites.

The crystal structure of pyruvate phosphate dikinase, a histidyl multiphosphotransfer enzyme that synthesizes adenosine triphosphate, reveals a three-domain molecule in which the phosphohistidine domain is flanked by the nucleotide and the phosphoenolpyruvate/pyruvate domains, with the two substrate binding sites approximately 45 angstroms apart. The modes of substrate binding have been deduced by analogy to D-Ala-D-Ala ligase and to pyruvate kinase. Coupling between the two remote active sites is facilitated by two conformational states of the phosphohistidine domain. While the crystal structure represents the state of interaction with the nucleotide, the second state is achieved by swiveling around two flexible peptide linkers. This dramatic conformational transition brings the phosphocarrier residue in close proximity to phosphoenolpyruvate/pyruvate. The swiveling-domain paradigm provides an effective mechanism for communication in complex multidomain/multiactive site proteins.

Amino Acid Sequence↗

PubMed1996

Genotoxicity and DNA adduct formation of incense smoke condensates: comparison with environmental tobacco smoke condensates.

Indoor air pollution has now been recognized as a potentially important problem for public health, since people spend most of their day in closed environments. Incense burning is possibly associated with elevated risks of leukemia and brain tumor in children from the epidemiological studies. Thus, evaluation of the genotoxicity of smoke condensates from incense burning is needed. We examined the genotoxicity of incense smoke condensates (ISC) using the Ames test in S. typhimurium strains with different mutagenic specificity and level of metabolic enzyme, the SOS chromotest in E. coli PQ37, and sister chromatid exchange assay in Chinese hamster ovary cells (SCE/CHO). The genotoxicity of environmental tobacco smoke condensates (TSC) was also evaluated by the three assays to compare with the genotoxicity of ISC. ISC showed a positive response in TA98, but not in TA100. It suggested that ISC only contained frame shift mutagens. The mutagenicity of ISC in both strains of TA98NR with deficient nitroreductase and TA98/1,8-DNP6 with deficient O-acetyltransferase was markedly decreased compared to that in TA98 strain. However, the mutagenicity was enhanced in YG1024 with overexpression of O-acetyltransferase activity. Thus, nitroarenes seemed to be responsible in part for the mutagenicity of ISC. Interestingly, all of the four ISC and two TSC samples showed a dose-dependent genotoxic response in the SOS chromotest with E. coli PQ37 but a low SCE induction of those samples were observed in CHO cells. When the genotoxicity was analyzed based on the condensates per one gram of original samples, the genotoxicity of two TSC condensates in prokaryotic cells was higher than that of four ISC samples except for the genotoxicity of TSC-2 in TA98 strain. However, the genotoxicity of certain ISC in eukaryotic cells based on the SCE/CHO assay was higher than that of TSC. To compare the covalent binding of DNA reactive intermediates of ISC and TSC to S. typhimurium TA98, the DNA adducts were evaluated by the 32P-postlabeling method with butanol extraction version. Similar diagonal radioactive zone (DRZ) was observed between ISC and CSC. However, DNA adduct levels induced by TSC were much greater than that of ISC.

Acetyltransferases↗

PubMed1996

Potentiation of bradykinin-induced inositol phosphates production by cyclic AMP elevating agents and endothelin-1 in cultured astrocytes.

Cultured astrocytes express bradykinin (BK) receptors, which are coupled to phospholipase C (PLC) through G-protein to mediate phosphoinositide (PI) hydrolysis. The regulation of this BK receptor-G protein-PLC pathway by cAMP and endothelin-1 (ET-1) was explored by short-term (20 min) and long-term (24 h) treatment with 100 mu M dibutyryl cyclic AMP (dBcAMP) or 10 nM ET-1. Short-term treatment of cells with dBcAMP had no effect on BK-induced PI hydrolysis; however, long-term treatment resulted in potentiation of the BK response. Similar effects were seen after 10 mu M forskolin pretreatment of the cells. We further explored the site of action of 24 h dBcAMP pretreatment and found that AlF(4)-, ionomycin- or A3187-induced PI hydrolysis was not affected but (3H)BK binding was increased. These results indicate that the site of action of dBcAMP is the BK receptor and Scatchard plot analysis showed that the Bmax was increased but the Kd decreased. Cycloheximide (0.5 mu M) blocked the increase in (3H)BK binding, indicating that new synthesis of receptor protein might occur during 24 h pretreatment with dBcAMP. Twenty minutes pretreatment of cells with ET-1 resulted in desensitization of the ET-1 induced P1 response, while the BK response was unaffected. After 24 h pretreatment with ET-1, desensitization to ET-1 still occurred, while BK-induced PI hydrolysis was markedly potentiated. (3H)BK binding and AlF(4)--induced but not A23187- or ionomycin-induced PI hydrolysis were increased, indicating that the site of action of long-term ET-1 treatment was the BK receptor and G protein; Scatchard analysis showed an increase in Bmax but no effect on Kd. These effects were blocked by cycloheximide, indicating that new synthesis of both receptor protein and G protein might occur during 24 h pretreatment with ET-1. (3H)Thymidine uptake was inhibited or potentiated by dBcAMP and ET-1, respectively. Possible dBcAMP-induced differentiation and ET-1-induced proliferation may contribute to the increased expression of receptor proteins.

Aluminum Compounds↗