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Biomedical subjects

S C Chueh

Publications and source records attributed to S C Chueh.

At least 19 recordsLinked to original sources

Modified approach of hand-assisted laparoscopic nephroureterectomy for transitional cell carcinoma of the upper urinary tract.

Objectives. To report a modified approach for hand-assisted laparoscopic nephroureterectomy (HALNU).Methods. Seven patients with localized transitional cell carcinoma of the upper urinary tract underwent unilateral HALNU. Patients were placed in a 60 degrees oblique position during the entire procedure. Via a 7-cm Gibson incision on the lesion side, the distal ureterectomy and bladder cuff excision were done by an open method without opening the bladder. Then, with the surgeon's hand inserted into the peritoneal cavity by way of the same wound, HALNU was performed with two to three additional laparoscopic ports. The perioperative parameters were compared with those of 15 cases of conventional open nephroureterectomy.Results. Patients in the HALNU group had significantly less mean blood loss (140 versus 455 mL) and earlier resumption of oral intake (33 versus 61 hours), required fewer narcotics (38 versus 70 mg of morphine sulfate equivalent), and were discharged earlier (7.33 versus 9.1 days), with a faster convalescence to normal activity (3.7 versus 5.6 weeks; all P < 0.05). The total mean surgical time was 3.7 hours for the HALNU group.Conclusions. Our approach used the same incision to both excise the distal ureter and apply the hand-assist device. It also preserved the benefits of the minimal invasiveness of laparoscopic surgery compared with its open counterpart.

Aged↗

Expression and localization of human dopamine D2 and D4 receptor mRNA in the adrenal gland, aldosterone-producing adenoma, and pheochromocytoma.

Aldosterone secretion is evidently regulated by a dopaminergic inhibitory mechanism. Pharmacological characterization and autoradiographic studies revealed D2-like receptors in the adrenal cortex, especially in the zona glomerulosa. However, the subtype of the dopamine receptors involving this regulation has not been elucidated. To investigate which subtype of receptors expresses in the adrenal cortex, we examined the messages of D2-like receptors, D2, D3, and D4, by RT-PCR and in situ hybridization of adrenal glands and adrenal neoplasm. Both D2 and D4 receptors were expressed in normal adrenal glands, pheochromocytoma, and aldosterone-producing adenoma. However, the D2 receptors were not universally expressed, in contrast with the D4 receptors that were detected in all cases of aldosterone-producing adenoma and adrenal remnant. No D3 receptor message was detected by RT-PCR in any adrenal sample. Both D2 and D4 receptors were expressed in significant amounts in the adrenal medulla and pheochromocytoma. In the adrenal cortex, the expression of the D2 receptors was in the zona glomerulosa and zona reticularis, with no different signal intensities between the two zones. D4 receptors were mainly localized in the zona glomerulosa and, to a lesser extent, in the zona reticularis. Both receptors were expressed at low levels in the zona fasciculata. In aldosterone-producing adenoma, the expression of D2 and D4 was especially found in nonzona fasciculata-like cells. To elucidate which dopamine receptor regulates aldosterone secretion, the effects of specific D2 and D4 antagonists, raclopride and clozapine, respectively, were examined in cultured NCI-H295 cells. Dopamine further increased angiotensin II-induced aldosterone secretion by 20%. In the presence of 1 microM dopamine and angiotensin II, 10(-5)-10(-7) M clozapine decreased aldosterone levels by 40-55%. The decrease in aldosterone secretion by clozapine was completely reversed when raclopride was added simultaneously. These data suggest that dopamine exerts dual effects on aldosterone secretion in NCI-H295 cells. Activation of D4 receptors can increase aldosterone secretion, whereas an inhibitory effect is mediated via D2 receptors. In summary, we demonstrated the existence of both D2 and D4 receptors in the human adrenal gland and adrenal neoplasm. Both receptors play significant roles in the modulation of aldosterone secretion, but in opposite directions.

Adenoma↗

Effectiveness of transperitoneal and trans-retroperitoneal laparoscopic adrenalectomy versus open adrenalectomy.

PURPOSE: This study compared the effectiveness of laparoscopic adrenalectomy, using either a transperitoneal or trans-retroperitoneal approach, with that of open adrenalectomy in patients with benign adrenal tumors. METHODS: From February 1995 to April 2000, laparoscopic adrenalectomy was performed on 31 patients with adrenal tumors, including 16 aldosteronomas, 10 Cushing's adenomas, three nonfunctioning tumors, and two pheochromocytomas. A lateral trans-retroperitoneal approach was used for the first 16 patients and a lateral transperitoneal approach was used for the last 15 patients. Twenty-one patients who received open adrenalectomy during the same period served as a control group. Comparisons were made between laparoscopy and open groups, and between transperitoneal and trans-retroperitoneal groups. RESULTS: Conversion to open adrenalectomy was necessary in two cases--both in the trans-retroperitoneal group during the first 2 years of the study period. No other intraoperative complications occurred and blood transfusion was not used. Compared with the open group, the laparoscopic group had less blood loss (71 vs 124 mL), resumed oral feeding earlier (28 vs 60 hr), required less postoperative narcotics (45 vs 120 mg meperidine), and had shorter postoperative hospital stays (4.9 vs 7.6 days) (all p < 0.05). The mean operative time was longer in the laparoscopic group (203 vs 123 min, p < 0.001). There were no significant differences between the transperitoneal and trans-retroperitoneal laparoscopy groups in any of the studied parameters, except that the operative time was longer in the trans-retroperitoneal laparoscopy group (244 vs 166 minutes, p < 0.01). CONCLUSIONS: Decreased blood loss, less postoperative pain, earlier resumption of oral feeding, and shorter hospital stays were achieved in patients undergoing laparoscopic adrenalectomy. These findings indicate that laparoscopic adrenalectomy is the treatment of choice for benign adrenal tumors. The transperitoneal approach yielded shorter operative time than the trans-retroperitoneal approach, because it offered a clearer view and familiar landmarks.

Adrenalectomy↗

Dual effects of ouabain on the regulation of proliferation and apoptosis in human prostatic smooth muscle cells.

PURPOSE: To elucidate the role of ouabain in the pathophysiology of benign prostatic hyperplasia we examined the effects of ouabain on the proliferation and apoptosis of human prostatic smooth muscle cells. MATERIALS AND METHODS: Primary cultures of human prostatic smooth muscle cells were obtained from 7 patients with bladder outlet obstruction caused by benign prostatic enlargement. A cell proliferation study was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay method to examine the effects of different concentrations of ouabain and various inhibitors. Western blot analysis was done to determine mitogen activated protein kinase (MAPK) activation. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling reaction method and caspase-3 activity assay were also performed to examine the apoptotic mechanism. RESULTS: Ouabain exhibited a modest but significant proliferative effect in nanomolar concentrations; whereas it induced cell apoptosis at higher concentrations. Ouabain caused rapid activation of p42/44 MAPKs. The proliferative effect of ouabain was completely flattened by W-7 and MAPK kinase (MEK) inhibitor, suggesting the requirement of Ca(2+) mobilization and the involvement of the MEK-p42/44 MAPK cascade. The cytotoxic effect by ouabain was defined as apoptosis and necrosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling reaction technique and lactate dehydrogenase release assay, respectively. In addition, ouabain induced profound caspase-3 activity in the cytotoxic concentrations and DEVD-CHO reversed the cytotoxic action to ouabain, demonstrating the involvement of caspase-3 activation in the cytotoxic action. CONCLUSIONS: Ouabain at different concentrations caused dual effects on proliferation and apoptosis in human prostatic smooth muscle cells. At low concentrations ouabain promoted cell proliferation via a Ca(2+) dependent mechanism and activation of the MEK-p42/44 MAPK pathway; whereas it induced cell apoptosis via the activation of caspase-3 activity at higher concentrations.

Analysis of Variance↗

Effects of ouabain on tension response and [3H]noradrenaline release in human prostate.

PURPOSE: The activity of Na+/K+ ATPase is a crucial factor in lots of functions of vascular and nonvascular smooth muscles. However, its role in muscle contractility of human prostate has not been well elucidated. In this context, we have examined the effect of ouabain on the contractile response and noradrenaline release in human prostate to clarify the role of cardiac glycoside in the pathophysiology of bladder outlet obstruction associated by benign prostatic enlargement. MATERIALS AND METHODS: Human prostatic tissues (n = 12) were obtained at operation from males by open prostatectomy (n = 2) or transurethral resection of the prostate (n = 10). The effect of ouabain on muscle contraction and [3H]noradrenaline release was studied in human prostatic tissue. The action mechanism following the administration of ouabain was also examined. RESULTS: Ouabain concentration-dependently induced a gradual contraction in human prostate and this delayed contraction was significantly blocked by prazosin other than the other receptor antagonists. In parallel experiments, ouabain also caused a concentration-dependent gradual increase in [3H]noradrenaline release, which was extracellular Ca2+-dependent. Furthermore, ouabain-induced [3H]noradrenaline release increased, in a concentration-dependent manner, with increasing Na+ concentrations from 25 to 140 mM. Moreover, K+-free Krebs solution could mimic the [3H]noradrenaline release action to ouabain. CONCLUSIONS: Ouabain may induce an increase in tension response in human prostate, and this effect is due mainly to an increase in noradrenaline release via an effect on the Na+-dependent Ca2+ influx system.

Cardiotonic Agents↗

Diagnosis of bladder cancer using telomerase activity in voided urine.

BACKGROUND AND PURPOSE: Telomerase is an essential enzyme for cellular immortality and tumorigenesis. Reactivation of telomerase is associated with many primary cancers. We evaluated the accuracy of a modified immunodiagnostic technique based on the telomeric repeat amplification protocol (TRAP) assay, by semi-quantitative measurement of telomerase activity in exfoliated urothelial cells in voided urine from patients with bladder cancer. METHODS: Telomerase activity was assayed in centrifuged urine cell pellets from 17 bladder cancer patients and from 32 patients with benign bladder diseases. Each specimen was collected from a 50-mL sample of single voided urine obtained before surgery, and telomerase activity was detected using a telomerase polymerase chain reaction and enzyme-linked immunosorbent assay (PCR-ELISA) protocol. Results of pathologic study, urine cytologic examination, and urine telomerase activity were determined independently. RESULTS: The cut-off value for relative telomerase activity was set at 0.059, which provided an optimal diagnostic accuracy of 88% (n = 49). At this cut-off value, the sensitivity and specificity for urine telomerase in bladder cancer were 82% (n = 17) and 91% (n = 32), respectively. Telomerase activity was found in 11 low-grade tumors and six high-grade tumors, whereas negative results for telomerase activity were found in urothelial cells of patients with inguinal hernia, urinary stones, acute urinary tract infection, or chronic cystitis. Only five cytology samples from the same patients were positive for bladder cancer. The difference in these two detection rates was significant (p = 0.002). CONCLUSION: The results of this study indicate that the measurement of telomerase activity from voided urine using our modified semi-quantitative PCR-ELISA technique may help provide earlier diagnosis of bladder cancer and earlier postoperative indication of recurrence.

Adult↗

Prophylaxis of acute renal allograft rejection using FTY720 in combination with subtherapeutic doses of cyclosporine.

BACKGROUND: In rodent transplant models, FTY720 exerts a synergistic affect with cyclosporine (CsA) to prolong allograft survival. The present experiments sought to test this combination in subhuman primates. METHODS: Cynomolgus monkeys were transplanted with kidney allografts that were incompatible in mixed lymphocyte culture reactions. The animals were treated with daily intramuscular injections of CsA using doses selected to maintain whole blood trough concentrations at therapeutic values between 40 and 200 ng/ml. The 4 experimental groups included CsA without or with 0.1, 0.3, or 1 mg/kg/day FTY720 delivered daily by intravenous bolus injection. Therapeutic effects were suggested both by the graft histology of biopsy within the first 10 posttransplant days and by the length of host survival. RESULTS: Whereas recipients treated with CsA alone rejected kidney allografts at a median survival time of 8.5 days (n=4), those treated with either 0.1 or 0.3 mg/kg/day FTY720 in addition to CsA showed significant prolongation of kidney allograft survival to 71 days (n=3; P<0.04) or 63 days (n=5; P<0.05), respectively. The hosts in the 1.0 mg/kg/day FTY720 group survived 48 days, with 2 of 5 recipients succumbing at 9 or 17 days postgraft, suggesting possible complications caused by overimmunosuppression. Biopsies of the 0.1 mg/kg/day FTY720 group on posttransplant day 7 documented mild to moderate rejection (grade I), indicated by multiple focal areas of tubular destruction. The histology results of transplants in the 0.3 or 1 mg/kg/day FTY720 group showed only minimal interstitial inflammatory infiltrates (borderline grade), with no evidence of tubular or arterial damage. Serum creatinine values among the animals in the 0.1 mg/kg/day FTY720 group showed increases in 2 of 3 recipients by day 20 and in the third by day 41 postgraft. Among the 0.3 mg/kg/day FTY720 group, 3 of 5 recipients maintained baseline creatinine values to 45 days postgraft; 1 recipient had stable kidney function for 120 days postgraft. CONCLUSIONS: Addition of FTY720 therapy to a subtherapeutic CsA immunosuppressive regimen delays the rejection of renal allografts in subhuman primates.

Acute Disease↗

Microspheres of hydroxyapatite/reconstituted collagen as supports for osteoblast cell growth.

Microspheres comprised of particulate hydroxyapatites dispersed in fibrous collagen matrices were prepared. The procedure involved the droplet formation of hydroxyapatite/collagen mixture emulsified in olive oil, followed by the reconstitution of collagen in the presence of hydroxyapatite particles at 37 degrees C. Various sizes of microspheres could be obtained by controlling the stirring speed of the emulsified mixture. By increasing the stirring speed from 200 to 350 and 500 rpm, the average diameter of the microspheres decreased from 1038 to 513 and 226 microm, respectively. The sizes of the microspheres reduced substantially to a range of 141 microm when 2%. Span 85 was present in the emulsion mixture stirring at 200 rpm. The microspheres thus obtained can be used as carriers to support the growth of osteoblast cells. Osteoblast cells derived from calvaria proliferated from 1.5 x 10(5) to 4.5 x 10(5) cells/ml in 7 days. Correspondingly, the alkaline phosphatase activity increased 6 fold during this period. These results suggested that the hydroxyapatite/collagen microspheres could be used as the filling materials for bone defect.

Animals↗

The influence of contact alignment of the tibiofemoral joint of the prostheses in in vitro biomechanical testing.

OBJECTIVE: To investigate the influence of contact alignment of the tibiofemoral joint of the prostheses in in vitro biomechanical testing. DESIGN: An experimental set-up was used to measure the total contact areas of the tibiofemoral joint of the prostheses subjected to a compressive load, and the malalignment situations were simulated. BACKGROUND: The contact alignment of the femoral component related to the tibial component in the literature was not described clearly and the effect of malalignment on the testing method has not been reported well. METHODS: Three commercial knee prostheses (Omnifit, Genesis, and AMK) were used for testing under a compression load (3000 N) at flexion 0 degrees and 10 degrees. After aligning the normal contact alignment, the simulated malalignment was done to evaluate the influence on the total contact areas in these conditions relative to the normal contact alignment. The simulated malalignment includes the medial-lateral translation (0.5 and 1 mm), anterior-posterior translation (2 and 4 mm) and internal-external rotation (1 degrees, 3 degrees and 5 degrees ) of the femoral component relative to the tibial component. RESULTS: The ratios of total contact areas of malalignment relative to normal contact alignment ranged from 1.06 to 0.93 in medial-lateral malalignment in these three prostheses. In anterior-posterior malalignment, the ratios ranged from 0.69 to 0.79 in Omnifit, 0.93-0. 96 in Genesis and 0.96-1.04 in AMK. In internal-external malrotation, the ratios ranged from 0.90 to 1.03 in these prostheses. CONCLUSIONS: This study proposes that contact alignment would affect the contact characteristics, especially in anterior-posterior alignment when high conformity knee prosthesis is tested. The contact alignment must be standardized in the procedure in in vitro biomechanical testing, which will be more objective to evaluate the contact characteristics of different knee prostheses. RELEVANCE: This study revealed the importance of contact alignment of the tibiofemoral joint of the prosthesis in in vitro biomechanical testing. Many published reports of the biomechanical evaluations on different designs of knee prostheses would show different results due to contact alignment. Furthermore, this study indicates that the ideal contact characteristics of the tibiofemoral joint in original design will be changed when the prosthesis under the malalignment condition which was caused by surgery technique or soft tissues imbalance.

Biomechanical Phenomena↗

Cell proliferation in human prostatic smooth muscle cells involves the modulation of protein kinase C isozymes.

We have examined the role of protein kinase C in the regulation of foetal-calf serum-stimulated cell proliferation in human prostatic smooth muscle cells. The data showed that the proliferative effect to foetal-calf serum (10%, v/v) was partially inhibited by 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo (2,3-a) pyrrolo (3,4-c)-carbazole (Go-6976), a selective Ca2+-dependent protein kinase C inhibitor, suggesting that Ca2+-dependent protein kinase C isozymes might play roles in this proliferative regulation. Additionally, foetal-calf serum caused a significant translocation of protein kinase C-betaII and -epsilon from a cytosolic to a membrane distribution. These findings combined with the aforementioned functional experiments suggest that foetal-calf serum-stimulated cell proliferation might involve the activation of protein kinase C-betaII in human prostatic smooth muscle cells; however, the role of protein kinase C-epsilon in mediating cellular functions other than cell proliferation remains further investigation in these cells.

Carbazoles↗

Antiproliferative effect in human prostatic smooth muscle cells by nitric oxide donor.

We obtained a primary culture of prostatic cells through explantation from patients with benign prostatic hyperplasia. Structural morphology, immunohistochemical staining, and growth characteristics of these cells demonstrate that they are consistent with the population of smooth muscle cells (SMCs). We examined the influence of a nitric oxide donor, sodium nitroprusside (SNP), on the regulation of human prostatic SMC proliferation. SNP exhibited a concentration-dependent (0.1-10 microM) inhibition of fetal calf serum-induced proliferation in human prostatic SMCs. In addition, growth-inhibitory responses to 8-bromo-cGMP (1-30 muM) were observed. However, the responses to SNP were significantly diminished by the presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (3 microM; a selective guanylate cyclase inhibitor). Furthermore, SNP induced an increased concentration-dependent accumulation of intracellular cGMP in human prostatic SMCs. After 48-hr period of deprivation of serum, cells were restimulated with serum to permit cell cycle progression. The addition of SNP (10 microM) at various times after the addition of serum to serum-deprived cells showed maximal inhibition of cell proliferation even when added 6 hr after the serum. This blocking effect of cell cycle progression was lost gradually as the delay from serum to SNP application increased from 6 to 18 hr. The membrane-associated protein kinase C (PKC) activity was studied in human prostatic SMCs; results showed that fetal calf serum (10%, v/v) significantly increased membrane-associated PKC activity. SNP (10 muM), which had little effect on basal kinase activity, completely abolished serum-induced augmentation of PKC activity. Therefore, we suggest that SNP mediates its antiproliferative effect by the inhibition of PKC activity on human prostatic SMCs; furthermore, its antiproliferative effect occurs at the early G1 phase of the cell cycle.

Apoptosis↗