Biomedical subjects

C J Tseng

Publications and source records attributed to C J Tseng.

At least 37 records · Page 2Linked to original sources

PubMed2000

Intra-striatal infusion of D-amphetamine induces hydroxyl radical formation: inhibition by MK-801 pretreatment.

Recent evidence suggests that free radicals can be produced in the brain following systemic administration of repeated or high doses of D-amphetamine (AMPH). However, it has been proposed that the toxic effects of AMPH are mostly secondary to AMPH-induced hyperthermia, and agents that protect against AMPH neurotoxicity do so by blocking AMPH-induced hyperthermia or causing hypothermia. In this study, we examined the effects of AMPH on the formation of hydroxyl radicals (*OH) following its infusion into the rat striatum via a microdialysis probe. We found that intra-striatal perfusion of AMPH (10 microM) caused an increased formation of hydroxyl radicals but did not raise the core temperatures of the rats. Pretreatment with the NMDA antagonist MK-801 (0.5 mg/kg) attenuated hydroxyl radical production elicited by AMPH infusion, although core body temperatures in AMPH-treated rats were not significantly altered. Additionally, infusion of AMPH in the striatum increased extracellular dopamine concentration and this effect was potentiated by MK-801 pretreatment. Thus, these results demonstrate that direct infusion of AMPH in the striatum induces hydroxyl radical production without causing hyperthermia, and also imply that activation of glutamate NMDA receptors mediates, at least in part, AMPH-induced hydroxyl radical formation in the rat striatum.

Animals↗

PubMed2000

Calmidazolium-induced rises in cytosolic calcium concentrations in Madin Darby canine kidney cells.

The effect of calmidazolium on Ca(2+) signaling in Madin Darby canine kidney (MDCK) cells was investigated using fura-2 as a Ca(2+) probe. Calmidazolium at 2-5 microM increased [Ca(2+)](i) concentration dependently. The [Ca(2+)](i) rise induced by 2-5 microM calmidazolium comprised an immediate rise and a slow decay. External Ca(2+) removal partly inhibited the Ca(2+) signals, suggesting that calmidazolium activated external Ca(2+) influx and internal Ca(2+) release. In Ca(2+)-free medium, pretreatment with 3 microM calmidazolium abolished the Ca(2+) release induced by 1 microM thapsigargin, an endoplasmic reticulum Ca(2+) pump inhibitor, and, vice versa, pretreatment with thapsigargin inhibited calmidazolium-induced Ca(2+) release. This indicates that thapsigargin-sensitive Ca(2+) store was the source of calmidazolium-induced Ca(2+) release. Calmidazolium (3 microM) induced Mn(2+) quench of fura-2 fluorescence at 360 nm excitation wavelength, which was suppressed by 0.1 mM La(3+). Addition of 3 mM Ca(2+) increased [Ca(2+)](i) after pretreatment with 3-5 microM calmidazolium in Ca(2+)-free medium. This implies that calmidazolium activated concentration-dependent capacitative Ca(2+) entry. Calmidazolium (3 microM) augmented the capacitative Ca(2+) entry induced by 1 microM thapsigargin or 0.1 mM ATP by 38%. Calmidazolium (3 microM)-induced Ca(2+) release was blocked by pretreatment with 40 microM aristolochic acid and 2 microM U73122 (2 microM) to inhibit phospholipase A(2) and phospholipase, respectively, but pretreatment with 0.1 mM propranolol to inhibit phospholipase D had no effect. This suggests that calmidazolium induced internal Ca(2+) release in a manner dependent on phospholipases C- and A(2)-coupled events.

Adenosine Triphosphate↗

PubMed2000

The usefulness of cystoscopy in the staging of cervical cancer.

OBJECTIVE: The aim of this study was to clarify the usefulness of cystoscopy in the staging of cervical cancer and to evaluate the clinical indications for performing ureteric catheterization to rule out ureteral obstruction in cervical cancer. METHODS: Both rigid cystoscopy and CT were performed before treatment in patients with cervical cancer of FIGO stage IB or greater. Cystoscopically directed biopsy specimens were taken from all areas in the bladder which were suspected of cancerous development. If a jet of urine spurting from each ureteral orifice was not found, a ureteric catheter was inserted into the orifice to rule out ureteral obstruction. The cystoscopic findings were compared with a CT examination. RESULTS: A total of 100 patients were included in the study (mean age 59 years). There were 30 stage IB cancers, 20 stage IIA, 17 stage IIB, 5 stage IIIA, 18 stage IIIB, and 10 stage IV. A total of 90 patients had squamous cell carcinomas and 10 had adenocarcinomas. Cystoscopy identified 8 patients with bladder invasion including 1 stage IIIA, 2 stage IIIB, and 5 stage IV. All of these patients had CT indication of possible invasion. CT indication of possible invasion was proved to be false by cystoscopy in 2 patients. Both the sensitivity and the negative predictive value of CT for bladder invasion were 100%. Of the 14 patients in whom ureteral obstruction was diagnosed by ureteric catheterization, 11 cases were indicated by CT scan, but for the other 3 patients CT found no significant ureteral obstruction. CONCLUSIONS: The results of this study suggest that cystoscopy is indicated only in cervical cancer patients for whom CT examination indicates possible bladder invasion. In addition, the results suggest that placement of ureteric catheterization using cystoscopy to rule out ureteral obstruction is not indicated in the staging of cervical cancer.

Adenocarcinoma↗

PubMed2000

Novel effects of clotrimazole on Ca2+ signaling in Madin Darby canine kidney cells.

The effect of clotrimazole on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca2+ indicator. Clotrimazole (1-30 microM) induced a concentration-dependent [Ca2+]i increase. The [Ca2+]i increase comprised an initial rise and a slow decay. External Ca2+ removal partly inhibited the Ca2+ signals by reducing both the initial rise and the decay phase, indicating that clotrimazole triggered both Ca2+ influx and Ca2+ release. Pretreatment with 30 microM clotrimazole in Ca2+-free medium abolished the Ca2+ release induced by thapsigargin (1 microM), an endoplasmic reticulum Ca2+ pump inhibitor, and conversely, pretreatment with thapsigargin prevented clotrimazole from releasing more Ca2+. This suggests that the thapsigargin-sensitive Ca2+ store is the source of clotrimazole-induced Ca2+ release. Clotrimazole (10 microM) triggered Mn2+ quench of fura-2 fluorescence which was partly inhibited by 1 mM La3+. Addition of 3 mM Ca2+ induced a [Ca2+]i increase after preincubation with 10 microM clotrimazole in Ca2+-free medium, indicating that clotrimazole activated capacitative Ca2+ entry. However, 10 and 30 microM clotrimazole inhibited 1 microM thapsigargin-induced capacitative Ca2+ entry by 21% and 74%, respectively. Pretreatment with 40 microM aristolochic acid to inhibit phospholipase A2 reduced 30 microM clotrimazole-induced Ca2+ release by 51%, but inhibiting phospholipase C with 2 microM U73122 had little effect. This implies that clotrimazole induces Ca2+ release in an IP3-independent manner, which could be modulated by phospholipase A2-coupled events.

Adenosine Triphosphate↗

PubMed2000

Fendiline increases [Ca2+]i in Madin Darby canine kidney (MDCK) cells by releasing internal Ca2+ followed by capacitative Ca2+ entry.

The effect of fendiline, a documented inhibitor of L-type Ca2+ channels and calmodulin, on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was investigated using fura-2 as a Ca2+ probe. Fendiline at 5-100 microM significantly increased [Ca2+]i concentration-dependently. The [Ca2+]i rise consisted of an initial rise and a slow decay. External Ca2+ removal partly inhibited the Ca2+ signals induced by 25-100 microM fendiline by reducing both the initial rise and the decay phase. This suggests that fendiline triggered external Ca2+ influx and internal Ca2+ release. In Ca(2+)-free medium, pretreatment with 50 microM fendiline nearly abolished the [Ca2+]i rise induced by 1 microM thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor, and vice versa, pretreatment with thapsigargin prevented fendiline from releasing internal Ca2+. This indicates that the internal Ca2+ source for fendiline overlaps with that for thapsigargin. At a concentration of 50 microM, fendiline caused Mn2+ quench of fura-2 fluorescence at the 360 nm excitation wavelenghth, which was inhibited by 0.1 mM La3+ by 50%, implying that fendiline-induced Ca2+ influx has two components separable by La3+. Consistently, 0.1 mM La3+ pretreatment suppressed fendiline-induced [Ca2+]i rise, and adding La3+ during the rising phase immediately inhibited the signal. Addition of 3 mM Ca2+ increased [Ca2+]i after preincubation with 50-100 microM fendiline in Ca(2+)-free medium. However, 50-100 microM fendiline inhibited 1 microM thapsigargin-induced capacitative Ca2+ entry. Pretreatment with 40 microM aristolochic acid to inhibit phospholipase A2 inhibited 50 microM fendiline-induced internal Ca2+ release by 48%, but inhibition of phospholipase C with 2 microM U73122 or inhibition of phospholipase D with 0.1 mM propranolol had no effect. Collectively, we have found that fendiline increased [Ca2+]i in MDCK cells by releasing internal Ca2+ in a manner independent of inositol-1,4,5-trisphosphate (IP3), followed by external Ca2+ influx.

Animals↗

PubMed2000

Cracking the auditory genetic code: part II. Syndromic hereditary hearing impairment.

OBJECTIVE: The application of molecular genetic techniques to the study of hereditary hearing impairment has contributed significantly to our understanding of auditory physiology and disease processes. This article reviews the current state of our knowledge regarding the genes associated with syndromic hereditary hearing impairment. DATA SOURCES: Data were obtained from the Medline database and the internet. STUDY SELECTION: Articles relevant to genetics of syndromic deafness were selected. DATA EXTRACTION: Data pertaining to phenotypes, location of genes, identification of genes, and implications for hearing were extracted. CONCLUSION: Significant progress has been made in understanding the molecular pathogenesis of deafness.

Gene Expression↗

PubMed2000

Novel effects of propranolol. Release of internal Ca(2+) followed by activation of capacitative Ca(2+) entry in Madin Darby canine kidney cells.

The effect of propranolol on Ca(2+) signalling in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Propranolol increased cytosolic free Ca(2+) levels ([Ca(2+)](i)) in a concentration-dependent manner between 0.1 and 1 mM. The response was partly inhibited by external Ca(2+) removal. In Ca(2+)-free medium pretreatment with 0.2 mM propranolol partly inhibited the [Ca(2+)](i) rise induced by 1 microM thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+) pump; but pretreatment with thapsigargin abolished propranolol-induced Ca(2+) release. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) rise after pretreatment with 0.2 mM propranolol in Ca(2+)-free medium. Propranolol (0.2 mM) inhibited 25% of thapsigargin-induced capacitative Ca(2+) entry. Suppression of 1,4,5-trisphosphate (IP(3)) formation by 2 microM U73122, a phospholipase C inhibitor, did not alter 0.2 mM propranolol-induced internal Ca(2+) release. Propranolol (1 mM) also increased [Ca(2+)](i) in human neutrophils. Collectively, we have found that 0.2 mM propranolol increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from thapsigargin-sensitive Ca(2+) stores in an IP(3)-independent manner, followed by Ca(2+) influx from external space. Independently, propranolol was able to inhibit thapsigargin-induced capacitative Ca(2+) entry.

Animals↗

PubMed2000

Modulatory effects of carbon monoxide on baroreflex activation in nucleus tractus solitarii of rats.

Recent studies suggest that carbon monoxide (CO), which is produced in significant quantities in many brain regions, may function as a neurotransmitter. Heme oxygenase catalyzes the metabolism of heme to CO and biliverdin; however, the physiological role of CO in central cardiovascular regulation was not well understood. In the present study, we evaluated the baroreflex response of CO in the nucleus tractus solitarii (NTS) of rats. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure and heart rate were monitored intra-arterially. Unilateral microinjection (60 nL) of hematin, a heme molecule cleaved by heme oxygenase to yield CO, into the NTS produced prominent dose-related depressor and bradycardic effects. Baroreflex responses were elicited by increasing doses of phenylephrine (10 to 30 microg/kg IV) before and after intra-NTS administration of zinc deuteroporphyrin 2,4-bis-glycol (ZnDPBG) (1 nmol), an inhibitor of heme oxygenase activity, or vehicle alone. The reflex bradycardia elicited by phenylephrine was significantly inhibited by pretreatment with ZnDPBG. Furthermore, the inhibitory effect of ZnDPBG on baroreflex activation was dose dependent. These results suggest CO formed by brain heme oxygenase plays a significant role in central cardiovascular regulation and that inhibition of heme oxygenase attenuated baroreflex activation.

Animals↗

PubMed2000

Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer.

PURPOSE: To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with that of radiotherapy (R/T) for bulky early-stage cervical cancer. PATIENTS AND METHODS: Women with previously untreated bulky (primary tumor >/= 4 cm) stage IB or IIA non-small-cell carcinoma of the uterine cervix were randomly assigned to receive either cisplatin 50 mg/m(2) and vincristine 1 mg/m(2) for 1 day and bleomycin 25 mg/m(2) for 3 days for three cycles followed by radical hysterectomy (NAC arm) or receive primary pelvic radiotherapy only (R/T arm). The ratio of patient allocation was 6:4 for the NAC and R/T arms. Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative. RESULTS: Of the 124 eligible patients, 68 in the NAC arm and 52 in the R/T arm could be evaluated. The median duration of follow-up was 39 months. Thirty-one percent of patients in the NAC arm and 27% in the R/T arm had relapse or persistent diseases after treatment, and 21% in each group died of disease. Estimated cumulative survival rates at 2 years were 81% for the NAC arm and 84% for the R/T arm; the 5-year rates were 70% and 61%, respectively. There were no significant differences in disease-free survival and overall survival. CONCLUSION: NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.

Adult↗

PubMed2000

W-7 induces [Ca(2+)](i) increases in Madin-Darby canine kidney (MDCK) cells.

The effect of W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride] on Ca(2+) signaling in Madin-Darby canine kidney cells was investigated. W-7 (0.1-1 mM) induced a [Ca(2+)](i) increase, which comprised an initial increase and a plateau. Ca(2+) removal inhibited the Ca(2+) signals by 80%, suggesting that W-7 activated external Ca(2+) influx and internal Ca(2+) release. Pretreatment with the mitochondrial uncoupler carbonylcyanide m-chlorophenylhydrazone (2 microM) and the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM) abolished the internal Ca(2+) release induced by 0.5 mM W-7; conversely, pretreatment with W-7 prevented thapsigargin and carbonylcyanide m-chlorophenylhydrazone from releasing internal Ca(2+). W-7 (0.2 mM) induced Mn(2+) quench of fura-2 fluorescence, which was inhibited by La(3+) (0.1 mM) by 80%. La(3+) (0.1 mM) partly inhibited 0.2 mM W-7-induced [Ca(2+)](i) increase. Addition of 5 mM Ca(2+) induced a significant [Ca(2+)](i) increase after pretreating with 0.2 to 1 mM W-7 in Ca(2+)-free medium for 5 min, suggesting that W-7 induced capacitative Ca(2+) entry. W-7 (0.5 mM) potentiated the capacitative Ca(2+) entry induced by 1 microM thapsigargin by 15%. Pretreatment with aristolochic acid (40 microM) to inhibit phospholipase A(2) reduced 0.5 mM W-7-induced internal Ca(2+) release and external Ca(2+) influx by 25 and 80%, respectively. Inhibition of phospholipase C with U73122 (2 microM) or inhibition of phospholipase D with propranolol (0.1 mM) had no effect on the internal Ca(2+) release induced by 0.5 mM W-7. It remains unclear whether W-7 induced [Ca(2+)](i) increases via inhibition of calmodulin. Three other calmodulin inhibitors (phenoxybenzamine, trifluoperazine, and fluphenazine-N-chloroethane) did not alter resting [Ca(2+)](i).

Animals↗

PubMed2000

High-risk HPV DNA detection by Hybrid Capture II. An adjunctive test for mildly abnormal cytologic smears in women > or = 50 years of age.

OBJECTIVE: To determine whether high-risk human papillomavirus (HPV) DNA testing could improve the detection of cervical intraepithelial neoplasia (CIN) and cancer in older women (> or = 50 years old) with mildly abnormal results on conventional cytology. STUDY DESIGN: The study was based on 119 patients aged over 50 (median, 62; range, 50-78) referred for colposcopy with Pap smears reported as atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesion (LSIL) from February 1997 to September 1998. The presence of high-risk HPV DNA (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was determined with the Hybrid Capture II (Digene, Inc., Silver Spring, Maryland) microplate method. Cytologic examination by Pap smear was based on the Bethesda System and, cervical biopsy was done via colposcopy. RESULTS: High-risk HPV DNA was demonstrated in 75.6% (34/45) of patients with LSIL and 52.7% (39/74) with ASCUS. Those who were HPV positive were significantly more likely to have CIN or cancer (odds ratio, 33.40; 95% confidence interval, 11.89-93.97; P < .0001). The sensitivity of HPV assay for detection of lesions more severe than CIN 2 was 100%, specificity 64.8%, positive predictive value 66.7% and negative predictive value 100%. CONCLUSION: The addition of a high-risk HPV DNA assay to cytologic examination appears to provide excellent sensitivity and negative predictive value for early detection of high grade CIN or cancer in older women with minimally abnormal Pap smears.

Age Factors↗

PubMed2000

Randomized, double-blind comparison of irbesartan and enalapril for treatment of mild to moderate hypertension.

BACKGROUND: Irbesartan is a newly developed angiotensin II receptor antagonist. Its antihypertensive efficacy and safety in Taiwanese patients with mild to moderate hypertension remains to be determined. METHODS: This was a multicenter, double-blind, randomized, parallel group study. One hundred and sixteen patients from three centers were enrolled. After a placebo lead-in period of 14 days, 55 patients (24-75 years-of-age) who had a mean seated diastolic blood pressure of 95 to 110 mmHg were randomized to once-daily treatment with irbesartan 150 mg or enalapril 10 mg. Doses were doubled at week 4 if trough seated diastolic blood pressure was 90 mmHg or more. Trough blood pressure was measured at zero, two, four and eight weeks of treatment. RESULTS: Both treatments lowered blood pressure with no significant difference in efficacy between treatment groups. Irbesartan 150 mg to 300 mg provided reductions in trough seated systolic and diastolic blood pressures at week 8 of -16.5 mmHg and -7.2 mmHg, respectively, with 36% of patients having a favorable response. Similarly, enalapril 10 mg to 20 mg reduced systolic and diastolic blood pressure by -10.6 mmHg and -5.0 mmHg, respectively, with a response rate of 43%. Headache, malaise and dizziness were the major adverse reactions observed in both groups. The incidence of drug-related cough was significantly higher with enalapril (18%) than with irbesartan (0%). CONCLUSIONS: Irbesartan 150 mg to 300 mg once daily was as effective in lowering blood pressure as enalapril 10 mg to 20 mg once daily. Both irbesartan and enalapril were well tolerated, while there was a significantly lower incidence of cough with irbesartan compared with enalapril.

Adult↗

PubMed2000

MK-886, a leukotriene biosynthesis inhibitor, as an activator of Ca(2+) mobilization in Madin-Darby canine kidney (MDCK) cells.

The effect of 3-¿1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl-2, 2-dimethylpropanoic acid (MK-886), a leukotriene biosynthesis inhibitor, on Ca(2+) mobilization in Madin- Darby canine kidney cells has been examined by fluorimetry using fura-2 as a Ca(2+) indicator. MK-886 at 0.5 to 25 microM concentration dependently increased ¿Ca(2+)(i). The ¿Ca(2+)(i) increase comprised an immediate initial rise and a slowly decaying phase. Ca(2+) removal inhibited the Ca(2+) signals by reducing both the initial rise and the decay phase, suggesting that MK-886 activated Ca(2+) influx and Ca(2+) release. In Ca(2+)-free medium, 10 microM MK-886 still increased ¿Ca(2+)(i) after pretreatment with carbonylcyanide m-chlorophenylhydrazone (CCCP; 2 microM), a mitochondrial uncoupler, and thapsigargin (1 microM), an endoplasmic reticulum Ca(2+) pump inhibitor. Conversely, pretreatment with MK-886 abolished CCCP- and thapsigargin-induced Ca(2+) release. This suggests that 10 microM MK-886 released Ca(2+) from the endoplasmic reticulum, mitochondria, and other stores. The addition of 3 mM Ca(2+) increased ¿Ca(2+)(i) after pretreatment with 10 microM MK-886 for 700 s in Ca(2+)-free medium, indicating that MK-886 induced capacitative Ca(2+) entry. This capacitative Ca(2+) entry was partly inhibited by SKF96365 (50 microM), by econazole (25 microM), and by inhibiting phospholipase A(2) with aristolochic acid (40 microM) but not by inhibiting phospholipase D with 0.1 mM propranolol. MK-886 (10 microM)-induced Ca(2+) release was not altered by inhibiting phospholipase C with U73122 (2 microM) but was inhibited by 50% by suppressing phospholipase D and phospholipase A(2) with propranolol (0.1 mM) and aristolochic acid (40 microM), respectively.

Animals↗

PubMed2000

Comparison of clinical behaviors and responses to radiation between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas of the cervix.

BACKGROUND: Adenocarcinomas/adenosquamous carcinomas (AC/ASC) are relatively uncommon histological subtypes in cervical cancer. In this study, we retrospectively compared the clinical behaviors and responses to radiation of squamous cell carcinomas (SCC) and AC/ASC in patients with stage I-IVA cervical cancer primarily treated by radiotherapy (RT). METHODS: Nine hundred twenty-eight patients with cervical cancer primarily treated with RT were included in this study. Ninety-four percent of the patients had SCC and 6% had AC/ASC. The association of histological subtype to various clinical parameters was assessed. Tumor response and failure patterns were analyzed, and the prognostic significance of histological subtype and other clinical parameters were evaluated by univariate and multivariate analyses. RESULTS: (1) Patients with AC/ASC had a significantly higher percentage of bulky I-IIA disease, a younger age (< 45 years), and an elevated carcinoembryonic antigen (CEA) level, but a lower percentage of elevated squamous cell carcinoma antigen (SCC-Ag) level, than patients with SCC. Hemoglobin (Hb) levels and lymph node status were not significantly different between SCC and AC/ASC patients. (2) A higher percentage of AS/ASC patients had residual induration 2 to 3 months after RT than those with SCC (40% vs. 21.6%, p = 0.008). Higher local failure rates were found for AC/ASC patients compared to SCC patients (38% vs. 15%, p = 0.001). (3) The 5-year disease-specific survival rate was 66% and 50% for SCC and AC/ASC patients, respectively (p = 0.016). Advanced stages, Hb levels lower than 10 g/dl, positive lymph nodes, AC/ASC histological subtype, and SCC-Ag levels higher than 10 ng/ml were independent prognostic factors for worse survival for all patients. For patients with AC/ASC in particular, only stage and positive lymph nodes were significant prognostic factors. CONCLUSION: Cervical cancer patients with AC/ASC are relatively younger and have a higher incidence of elevated CEA and a lower incidence of elevated SCC-Ag levels than those with SCC. For AC/ASC patients, the tumor responses to RT were relatively slow and poor. This group of patients had a worse survival rate than patients with SCC, mainly because of the higher incidence of uncontrolled local disease for AC/ASC patients.

Adenocarcinoma↗

PubMed1999

Nitric oxide signaling pathway mediates the L-arginine-induced cardiovascular effects in the nucleus tractus solitarii of rats.

We have previously demonstrated that L-arginine produces profound cardiovascular effects when microinjected into the nucleus tractus solitarii (NTS) of the rat. The present study extended our earlier work and examined further the underlying mechanisms of action of L-arginine in the NTS. Our results showed that intra-NTS microinjection of L-arginine (0.1-10 nmol) elicited dose-dependent depressor and bradycardic effects that were not significantly evoked by equivalent doses of D-arginine. The effects of L-arginine were blocked by pre-injection of 7-nitroindazole (0.02-1 nmol), a neuronal nitric oxide synthase inhibitor. Additionally, application of the calmodulin inhibitor W-7 (0.01-0.33 nmol) reduced cardiovascular responses to L-arginine (10 nmol) in a dose-dependent manner. Pre-injections of soluble guanylyl cyclase inhibitors, LY83583 (0.01-0.33 nmol) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 0.03-1 pmol) both suppressed the L-arginine-induced depressor and bradycardic effects. Finally, the cardiovascular effects of L-arginine in the NTS were attenuated by HA1004 (0.1-1 nmol), a cGMP-dependent protein kinase inhibitor, but not by the protein kinase C inhibitor H-7 (1 nmol). Taken together, the results indicate that the cardiovascular effects produced by L-arginine in the NTS are inhibited by pharmacological interventions that block nitric oxide production and cGMP-PKG signaling pathway within the nucleus.

Aminoquinolines↗

PubMed1999

Mechanisms of miconazole-induced rise in cytoplasmic calcium concentrations in Madin Darby canine kidney (MDCK) cells.

The effect of miconazole on intracellular calcium levels ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells was studied using fura-2 as the Ca2+ indicator. Miconazole increased [Ca2+]i dose-dependently at concentrations of 5-100 microM. The [Ca2+]i transient consisted of an initial rise, a gradual decay and an elevated plateau (220 s after addition of the drug). Removal of extracellular Ca2+ partly reduced the miconazole response. Mn2+ quench of fura-2 fluorescence confirmed that miconazole induced Ca2+ influx. The miconazole-sensitive intracellular Ca2+ store overlapped with that sensitive to thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, because 20 microM miconazole depleted the thapsigargin (1 microM)-sensitive store, and conversely, thapsigargin abolished miconazole-induced internal Ca2+ release. Miconazole (20-50 microM) partly inhibited the capacitative Ca2+ entry induced by 1 microM thapsigargin, measured by depleting intracellular Ca2+ store in Ca(2+)-free medium followed by addition of 10 mM CaCl2. Miconazole induced capacitative Ca2+ entry on its own. Pretreatment with 0.1 mM La3+ partly inhibited 20 microM miconazole-induced Mn2+ quench of fura-2 fluorescence and [Ca2+]i rise, suggesting that miconazole induced Ca2+ influx via two pathways separable by 0.1 mM La3+. Miconazole-induced internal Ca2+ release was not altered when the cytosolic level of inositol 1,4,5-trisphosphate (IP3) was substantially inhibited by the phospholipase C inhibitor U73122.

Animals↗

PubMed1999

Preoperative prognostic variables and the impact of postoperative adjuvant therapy on the outcomes of Stage IB or II cervical carcinoma patients with or without pelvic lymph node metastases: an analysis of 891 cases.

BACKGROUND: The purpose of this study was to investigate pretreatment variables that could predict prognosis and to evaluate the impact of postoperative adjuvant therapy on the outcomes of patients with Stage IB or II cervical carcinoma with or without pelvic lymph node metastases. METHODS: Eight hundred ninety-one patients with Stage IB or II cervical carcinoma who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment at a single institution were analyzed. Potential prognostic variables were studied. RESULTS: Among the variables that could be assessed before treatment, depth of cervical stromal invasion (determined by magnetic resonance imaging), clinical stage, tumor size, grade of differentiation, and DNA index (determined by flow cytometry) were independent predictors of outcome in multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk) were defined using these variables. Five-year recurrence free survival (RFS) rates for the low, intermediate, and high risk groups were 94.6%, 82.7%, and 62.3%, respectively (P = 0.0001), and overall survival (OS) rates were 98.4%, 84.5%, and 68.7%, respectively (P = 0.0001). Among patients with pelvic lymph node metastases who were free of parametrial extension, those who received postoperative chemotherapy or chemoradiotherapy had significantly better RFS (P = 0.017) and OS (P = 0.043) than those who received no adjuvant therapy. Among patients without pelvic lymph node metastases but at high risk of recurrence, those who received adjuvant radiotherapy had significantly better RFS (P = 0.015) and marginally improved OS (P = 0.087) compared with those who received no adjuvant therapy. CONCLUSIONS: A model containing assessable pretreatment variables for predicting the prognoses of patients with early stage cervical carcinoma was formulated. Subsets of patients for whom postoperative chemotherapy or radiotherapy might be beneficial were identified. The data from this retrospective review may be useful when future prospective trials of the treatment of early stage cervical carcinoma are designed.

Adult↗

PubMed1999

A further investigation of ATP-induced calcium mobilization in MDCK cells.

We have previously reported that La3+ inhibited the ATP-induced rise in intracellular Ca2+ levels ([Ca2+]i) measured by fura-2 fluorimetry in Madin Darby canine kidney (MDCK) cells. Here we further investigated the ATP-induced Ca2+ signal. ATP caused a rise in [Ca2+]i dose-dependently between 1 microM-1 mM. The rises induced by 10 microM-1 mM ATP were inhibited by Ca2+ removal. The pleateau phase of the ATP response was primarily maintained by Ca2+ influx because it was reduced or eliminated by Ca2+ removal. ATP failed to elevate [Ca2+]i after the endoplasmic reticulum Ca2+ store had been depleted by 2,5-di-tert-butylhydroquinone or cyclopiazonic acid, suggesting that the ATP-induced Ca2+ influx was capacitative Ca2+ entry. Capacitative Ca2+ entry was directly measured by addition of 5 mM CaCl2 to cells pretreated with ATP (0.1 mM) in Ca(2+)-free medium. This capacitative Ca2+ entry was inhibited by econazole (25 microM) or SKF96365 (50 microM). The ATP response was significantly enhanced by extracellular alkalization to pH 8 or pretreatment with gly-phe-beta-naphthylamide. Pretreatment with carbonylcyanide m-chlorophenylhydrazone (CCCP) or extracellular Na+ removal had no enhancement, implicating that efflux via plasmalemmal Ca2+ pumps (but not Na+/Ca2+ exchange) and buffering by lysosomes (but not mitochondria) might be involved in the decay of the ATP response.

Adenosine Triphosphate↗