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Biomedical subjects

S C Chueh

Publications and source records attributed to S C Chueh.

17 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Pretransplant test-dose pharmacokinetic profiles: cyclosporine microemulsion versus corn oil-based soft gel capsule formulation.

The purpose of this study was to compare the accuracy of pretransplant test-dose pharmacokinetic (PK) profiling after administration of the microemulsion (CsA-ME; Neoral) versus the corn oil-based (CsA-GC; Sandimmune) gel capsule formulations of cyclosporin A (CsA) to estimate posttransplant CsA bioavailability and to individualize starting drug doses. The absolute oral bioavailability (F), clearance rate (CL), average blood concentration (C[av]), peak concentration (Cmax), and time to Cmax (tmax) values were calculated from paired intravenous and oral pretransplant PK profiles of renal transplant candidates, using CsA-GC (n = 70) or CsA-ME (n = 70) administration. The initial posttransplant oral CsA dose was estimated by linear extrapolation of the observed pretransplant value to the target concentration. Because higher mean F (P < 0.0001), but not CL, values were observed in end-stage renal disease patients after CsA-ME compared with CsA-GC treatment, the predicted starting doses for each therapy were markedly different (P < 0.01). From posttransplant days 5 to 7, 54% of patients treated with CsA-ME had a mean dose-normalized C(av) (C(av)/dose, D) value within 20% of the target concentration, compared with 42% of patients treated with CsA-GC (P = 0.03). Administration of the predicted oral dose of CsA-ME produced a Cmax > 700 ng/ml in 90% of patients from days 2 to 4, and in 97% from days 5 to 7, whereas administration of the predicted oral dose of CsA-GC produced a Cmax > 700 ng/ml in only 64 and 82% of patients during these same time periods, respectively (both P < 0.05). The mean estimated posttransplant F value of CsA-ME was significantly higher than that of CsA-GC; even at postoperative day 5 the value for CsA-GC was significantly lower than the pretransplant estimate (P < 0.01). Therefore, CsA-ME pretransplant PK profiles yield more accurate predictions for appropriate starting drug doses than those of CsA-GC.

Administration, Oral↗
PubMed1998

Penile cancer in Taiwan--20 years' experience at National Taiwan University Hospital.

To analyze the characteristics and prognostic factors of penile cancer in Taiwanese, we retrospectively reviewed the clinical data of patients with a diagnosis of penile cancer treated during a 20-year period (1977-1996) at National Taiwan University Hospital (NTUH). Of 71 patients treated for penile cancer during the study period, 17 were referred from other hospitals or clinics. Our analyses focused on the 54 previously untreated patients. Growth on the penis was the main symptom in all cases. Palpable inguinal lymph nodes were found only in 14 patients. All 54 patients with primary tumors were treated surgically. Pathologic examination showed squamous cell carcinoma (SCC) in 43 cases, extra-mammary Paget's disease in three, verrucous carcinoma in three, Bowen's disease in two, cutaneous lymphoma in two and basal cell carcinoma in one. Twenty-six (48%) patients had stage I penile cancer, 13 (24%) had stage II, seven (13%) had stage III, and eight (15%) had stage IV cancer. The five-year survival rate was 78% among patients with SCC and 84% among those with nonsquamous malignancies (p = 0.80). The five-year cumulative survival rates according to Jackson's cancer stage were 100% for patients with stage I, 88.9% for those with stage II, 66.7% for those with stage III, and 0% for those with stage IV (p < 0.001). Tumor staging (p = 0.027) and adjuvant chemotherapy (p = 0.042) were found to be the most significant prognostic factors. Penile cancer accounted for 0.254% of all malignancies among male patients at the NTUH during the study period. Our findings indicate that penile cancer is uncommon in Taiwanese and its prognosis is closely related to tumor staging and management. Early diagnosis and appropriate treatment may lead to prolonged survival.

Adult↗
PubMed1997

Induction of tolerance toward rat cardiac allografts by treatment with allochimeric class I MHC antigen and FTY720.

BACKGROUND: The combination of FTY 720, a novel immunosuppressant, and allochimeric class I MHC proteins bearing donor-type amino acid (aa) epitope substitutions for host-type sequences induces tolerance of Wistar Furth (WF; RT1.Au) heart allografts in ACI (RT1.Aa) recipients. METHODS: Allochimeric alpha(1h)l58-80-RT1.Aa proteins were produced by substituting the allogeneic nucleotide sequence encoding 10 aa residues unique to the alpha1 helical (alpha1h) region of RT1.Al Lewis (Asp58, Arg62, Glu63, Gln65, Lys66, Gly69, Asn70, Asn73, Ser77, and Asn80) for native RT1.Aa residues. The RT1.Au and the RT1.Al haplotypes share four of these aa (Arg62, Glu63, Gln65, and Gly69). A baculovirus/Spodoptera frugiperda insect cell system was used to express the alpha(1h)l58-80-RT1.Aa proteins. RESULTS: The addition of a 3-day oral gavage of 0.05 mg/kg/day FTY720 to a single portal vein injection of 10 microg alpha(1h)l58-80-RT1.Aa protein induced permanent acceptance of WF heart allografts in 16 of 26 ACI recipients (>100 days); the alpha(1h)l58-80-RT1.Aa protein alone only modestly prolonged WF heart survival (13.8+/-0.8 days). The same tolerogenic protocol did not prolong the survival of third-party Brown Norway (RT1.An) heart allografts (14.3+/-2.5 days) compared with FTY720 alone (14.0+/-2.3 days; NS). Tolerant ACI recipients bearing primary WF heart allografts for more than 100 days accepted second WF hearts, but promptly rejected third-party Brown Norway heart grafts (9.3+/-1.5 days). The tolerant state was transferred to irradiated ACI rats (400 rad) with either purified T cells (4-10 x 10[7]) or serum (1-2 ml) from tolerant hosts, and was not broken by daily intraperitoneal injections of interleukin-2 (1000 U/day; 7 days). CONCLUSIONS: The combination of allochimeric protein with FTY720 induces transplantation tolerance, a state that may be associated with the appearance of donor-specific regulatory factors.

Animals↗
PubMed1996

Inhibition by tamsulosin of tension responses of human hyperplastic prostate to electrical field stimulation.

Tamsulosin (10(-10)-10(-9) M) or prazosin (10(-9)-10(-8) M) concentration dependently blocked the tension responses to electrical field stimulation (0.3 ms duration, 80 V and 20 Hz) in human hyperplastic prostate with lC50 values of (1.93 +/- 0.26) x 10(-10) M and (2.11 +/- 0.21) x 10(-9) M, respectively. The relative potency of tamsulosin with reference to prazosin was 10.96. The pA2 values for tamsulosin and prazosin against phenylephrine-induced contractions were 10.05 +/- 0.16 and 9.25 +/- 0.07, respectively. The relative potency of tamsulosin with reference to prazosin was 6.31. In the presence of prazosin to block alpha 1-adrenoceptor-mediated responses, nifedipine (10(-5) M), but not tamsulosin (10(-9) M), significantly blocked the tension responses in human hyperplastic prostate induced by increasing [Ca2+]o concentrations (10(-4) to 3 x 10(-3) M) in a Ca(2+)-free environment pre-depolarized with 60 mM K+. Additionally, the effects of prazosin and tamsulosin on electrical field stimulation-evoked [3H]noradrenaline release were studied on the S3/S2 ratios. It appeared that both drugs had little effect on this release reaction, with S3/S2 ratios of 0.96 +/- 0.02 and 0.90 +/- 0.02, respectively. These results indicate that tamsulosin is a potent antagonist against endogenous sympathetic stimulation in human hyperplastic prostate.

Adrenergic alpha-Agonists↗
PubMed1996

Ouabain-induced increases in resting tone of human hyperplastic prostate following repeated noradrenaline and electrical field stimulation.

1. The effect of ouabain on contractions to repeated noradrenaline stimulation and electrical field stimulation of human hyperplastic prostate was examined. Ouabain (1 microM) did not induce contractile response per se but progressively increased the resting tone (i.e., the tone between one noradrenaline stimulation, or electrical field stimulation, and the following) of human hyperplastic prostate. 2. The increased tone by ouabain following repeated noradrenaline stimulations or electrical field stimulation was fully relaxed by the removal of external calcium, and recovered following restoration of calcium. 3. The effect of noradrenaline on NA+ uptake was measured. Noradrenaline (10 microM) significantly increased the rate of Na+ accumulation in the presence of ouabain (1 microM); this stimulatory effect was almost completely blocked by prazosin (0.1 microM) and ethylisopropylamiloride (100 microM). In contrast, tetrodotoxin (1 microM) had no effect on noradrenaline-stimulated Na+ transport in human hyperplastic prostate. 4. Intracellular Na+ loading by noradrenaline (10 microM) in the presence of ouabain (1 microM) significantly increased the transmembrane Ca2+ uptake as compared with the absence of ouabain; however, nifedipine (1 microM) was ineffective on Ca2+ uptake under this condition. 5. Transmembrane CA2+ efflux was stimulated by noradrenaline (10 microM) in human hyperplastic prostate; this effect was significantly decreased in the presence of ouabain (1 microM). 6. It is suggested that the increased tone of human hyperplastic prostate following repeated excitation in the presence of ouabain is due to increased Ca2+ entry and reduced efflux of Ca2+ through the Na+/Ca+ exchange system as a consequence of Na+ pump inhibition by ouabain.

Adrenergic alpha-Agonists↗
PubMed1996

Simple nephrectomy by retroperitoneoscope.

Retroperitoneoscopic simple nephrectomy was successfully performed in 10 of 12 patients with nonfunctioning kidneys. The other two patients underwent traditional open surgery. The surgical procedures, technical pitfalls, surgical results and perisurgical complications of this simple retroperitoneoscopic approach are described. Retroperitoneoscopic nephrectomy is a viable alternative for simple nephrectomy and has the benefits of minimal invasiveness, more rapid convalescence and better quality of life for patients.

Aged↗
PubMed1996

Treating benign prostatic hyperplasia with finasteride in Chinese men: one-year experience.

To evaluate the long-term efficacy and safety of finasteride in the treatment of symptomatic benign prostatic hyperplasia (BPH), 50 patients with symptomatic BPH were initially evaluated in a double blind, placebo-controlled study for 6 months. The patients were then treated with finasteride in an open extension study in which all received the same dose of finasteride (5 mg/day) for another 6 months. Among the patients (n = 23) who completed the extension study, prostate volume was significantly reduced from baseline by 15%, maximum urine flow rate improved by 1.9 mL/second, symptom scores improved by 37% and serum prostatic specific antigen (PSA) level decreased by 1.34 ng/mL. Other than serum PSA level, these data differed insignificantly from data at the end of the first 6 months. The adverse events observed at the end of the first 6 months (two patients with decreased sexual libido and two with impotency) persisted throughout the study extension period. At the end of the 12 months study, one more patient reported decreased libido. The sustained clinical efficacy and low incidence of side-effects of daily treatment with finasteride 5 mg for 1 year indicate that finasteride is safe and effective for managing symptomatic BPH in Chinese men.

Aged↗
PubMed1996

Fournier's gangrene as the initial clinical manifestation of diabetes mellitus.

Fournier's gangrene is a true urosurgical emergency requiring prompt surgical intervention. Diabetes mellitus is not uncommon among the sufferers of Fournier's gangrene. In rare instances, Fournier's gangrene may present as the initial clinical manifestation of diabetes mellitus in an undiagnosed diabetic. An unknown, and hence uncontrolled, diabetic situation and its associated pathophysiologic changes will adversely aggravate the infectious process. Alertness to this possibility together with efforts to control the diabetes and urosurgically manage the gangrene afford the promise of successful cure.

Adult↗
PubMed1995

Characterization of alpha 1-adrenoceptor subtypes in tension response of human prostate to electrical field stimulation.

1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical field stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked these effects by only 50%. 3. The contractile responses of rat vas deferens and spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha 1A-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical field stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 microM), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5. The involvement of prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined. Clonidine (3 x 10-9 to 3 x 10- M) blocked concentration-dependently the contractile response to electrical field stimulation of human prostate and this inhibitory effect was reversed by yohimbine (10-7 M). Additionally, the inhibitory effect of CEC (3 x 10-6 to 3 x 10-4 M)to the nerve-mediated contraction was also partially reversed by yohimbine (10-7 M).6. It is suggested that the putative czA-adrenoceptors in human prostate may be functionally confined to the synaptic region whereas only minor populations of the putative alpha 1B- and/or alpha 1c-adrenoceptors exist in this region.

Adrenergic Antagonists↗
PubMed1994

Effects of dicentrine, a novel alpha 1-adrenoceptor antagonist, on human hyperplastic prostates.

The effects of dicentrine, an alpha 1-adrenoceptor antagonist, on human hyperplastic prostates were investigated by radioligand binding and in vitro isometric tension experiments. In human hyperplastic prostates, alpha 1-adrenoceptors were characterized by a binding assay using [3H]prazosin as a radioligand. Specific [3H]prazosin binding was saturable and of high affinity (Kd = 0.2 +/- 0.02 nM) with a maximal number of binding sites (Bmax = 55.2 +/- 3.2 fmol/mg protein). alpha-Adrenoceptor antagonists competed with [3H]prazosin for binding in the order: dicentrine > phentolamine > rauwolscine. Norepinephrine (0.3-100 microM) or phenylephrine (1-300 microM) produced gradual contractions of human hyperplastic prostates. The concentration-response curve of norepinephrine or phenylephrine was shifted in parallel to the right by dicentrine, consistent with a competitive blockade. The pA2 values of dicentrine against norepinephrine and phenylephrine were 8.04 +/- 0.09 and 8.33 +/- 0.11, respectively. These experiments were conducted to confirm that there was no interaction between alpha 1- and alpha 2-adrenoceptors in the tissue. Rauwolscine (1 microM) caused 1.7-fold, while dicentrine (0.1 microM) caused 15.8-fold shift of norepinephrine-induced contraction of human hyperplastic prostates. Combination of rauwolscine with dicentrine caused 17.8-fold shift of norepinephrine-induced prostatic tissue contraction. The contractile response to transmural field stimulation was abolished by pretreatment with tetrodotoxin, and suppressed concentration dependently by dicentrine or prazosin, whereas rauwolscine had little effect. It is concluded that dicentrine inhibits human hyperplastic prostate contractions in response to exogenous and endogenous adrenergic stimulation. Dicentrine may thus hold potential to relieve bladder outlet obstruction caused by benign prostatic hyperplasia via alpha 1-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗