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T F Lue

Publications and source records attributed to T F Lue.

At least 55 records · Page 3Linked to original sources
PubMed2000

Microsatellite alterations and loss of heterozygosity in Peyronie's disease.

PURPOSE: In the present study, we tested the hypothesis that microsatellite alterations (MSI) and loss of heterozygosity (LOH) are associated with Peyronie's disease. To test this hypothesis, we analyzed samples from patients with Peyronie's for MSI and LOH on chromosomes 3, 8 and 9 using 20 different genetic markers. MATERIALS AND METHODS: DNA was isolated from the penile fibrotic plaque, amplified using PCR, and analyzed for MSI and LOH on chromosomes 3, 8 and 9 using 20 different polymorphic markers (D3S1228, D3S1298, D3S1560, D3S1745, D3S2396, D3S647, D8S133, D8S255, D8S259, D8S260, D8S262, D8S285, D8S298, D8S507, D8S528, D9S162, D9S171, D9S1747, D9S1748, and D9S273). Only 10 primers (D3S1560, D3S647, D3S1298, D8S262, D8S260, D8S528, D9S171, D9S1747, D9S273 and D9S1748) showed MSI and LOH in Peyronie's samples. Microsatellite alterations and LOH were analyzed by a PCR-based technique developed in our laboratory. RESULTS: This study demonstrates a high frequency of MSI and LOH in Peyronie's disease. Fourteen of 35 cases (40%) showed MSI at a minimum of one locus, 6 of 35 cases (17%) at a minimum of 2 loci and three of 35 (8.5%) cases at three or more loci. D9S273 locus showed highest MSI when compared with other loci examined in this study. For LOH, 14 of 35 cases (40%) were observed at a minimum of one locus, 5 of 35 cases (14%) at minimum of two loci and one out of 35 cases (2.8%) showed LOH at three or more loci. The D3S1560 and D9S171 loci showed highest LOH when compared with all other loci examined in this study. CONCLUSION: This is the first report demonstrating that a high frequency of MSI and LOH is associated with Peyronie's disease, suggesting their role in the pathogenesis of this disease.

Adult↗
PubMed2000

Effect of a Chinese herbal medicine mixture on a rat model of hypercholesterolemic erectile dysfunction.

PURPOSE: We examine the effect of a Chinese herbal medicine mixture on erectile function in a rat model of hypercholesterolemic erectile dysfunction. MATERIALS AND METHODS: In this study 32, 3-month-old Sprague-Dawley rats were used. The 8 control animals were fed a normal diet and the remaining 24 were fed 1% cholesterol diet for 4 months. After 2 months herbal medicine was added to the drinking water of the treatment group of 16 rats but not the cholesterol only group of 8. Of the 16 rats 8 received 25 mg./kg. per day (group 1) and 8 received 50 mg./kg. per day (group 2) of Chinese herbal medicine mixture. Serum cholesterol levels were measured at 2 and 4 months. At 4 months erectile function was evaluated with cavernous nerve electrostimulation in all animals. Penile tissues were collected for electron microscopy, and to perform Western blot for endothelial nitric oxide synthase, neuronal nitric oxide synthase, basic fibroblast growth factor (bFGF) and caveolin-1. RESULTS: Serum cholesterol levels were significantly higher in animals fed the 1% cholesterol diet compared to controls at 2 and 4 months. Nevertheless, there was no significant difference among group 1 (145 +/- 30 mg./dl.), group 2 (157 +/- 20) and the cholesterol only group (143 +/- 15). Systemic arterial pressure was not significantly different between the animals that were fed the 1% cholesterol diet and the controls. During electrostimulation of the cavernous nerve peak sustained intracavernous pressure was significantly lower in the cholesterol only group (50 +/- 23 cm. H2O) compared to the control group. Conversely erectile function was not impaired in the herbal medicine treated rats. Electron microscopy showed many caveolae with fingerlike processes in the cavernous smooth muscle and endothelial cell membranes in control and treated rats but not in the cholesterol only group of rats. Western blot did not show a difference among groups in protein expression for endothelial nitric oxide synthase and neuronal nitric oxide synthase in penile tissue but caveolin-1 and bFGF protein expression was significantly higher in groups 1 and 2 than in the cholesterol only and control groups. CONCLUSIONS: Rats developed erectile dysfunction after being fed a 1% cholesterol diet for 4 months. Although serum cholesterol levels were similar in the cholesterol only rats and those treated with Chinese herbal medicine mixture, erectile response was significantly better in the treated group. The mechanism of the herbal medicine is unknown. High levels of bFGF and caveolin-1 expression in the treated group may protect the cavernous smooth muscle and endothelial cells from the harmful effect of high serum cholesterol.

Animals↗
PubMed2000

Pharmacotherapy for erectile dysfunction.

OBJECTIVE: To review current pharmacologic treatment options for erectile dysfunction. METHODS: Relevant literatures from the past two decades regarding the following treatments were reviewed: intracavemous injection, topical therapy, transurethral therapy and oral drugs. STUDY SELECTION: More than 125 originally identified articles were reviewed, and 45 were selected that especially addressed the stated purpose. RESULTS: Among the pharmacologic treatment options available, intracavemous injection therapy remains the most effective although the drop-out rate is high. Topical creams and gels have not been very successful. Transurethral alprostadil can be more effective if a constriction device is applied at the base of the penis. Oral sildenafil has the highest patient acceptance rate although systemic side effects can be a major drawback. CONCLUSIONS: Effective pharmacotherapies for ED of various etiologies are now available. However, proper evaluation of every patient should be performed before giving treatment so that a number of potentially life-threatening causes of erectile dysfunction would not be missed.

Alprostadil↗
PubMed1999

Bladder acellular matrix graft: in vivo functional properties of the regenerated rat bladder.

The purpose of this study was to determine whether the rat urinary bladder augmented by an acellular matrix graft can restore the bladder's low-pressure reservoir function and preserve normal micturition. After partial cystectomy (> 50%) and grafting with the bladder acellular matrix graft (BAMG), storage and voiding functions were monitored in 20 rats by means of a specially designed "micturition cage," leak-point cystography, and cystometry. After 4 months, sections (n = 6) were examined histologically to evaluate regeneration of bladder wall components within the BAMG. Bladder capacity and compliance increased progressively and were significantly higher in the grafted animals than in controls (partial cystectomy only), and volumes per void were significantly higher than in either control or normal animals. At 4 months, the regenerated urothelium, smooth muscle, blood vessels and nerves within the BAMG were qualitatively identical to normal bladder wall. Augmentation cystoplasty with the homologous BAMG leads to morphologic and functional rat bladder regeneration, thus enhancing low-pressure reservoir function and preserving normal micturition.

Animals↗
PubMed1999

Surgery for crural venous leakage.

A procedure for congenital or acquired crural venous leakage is described. A 3-in.-long inguinoscrotal incision is made about 1 in. lateral to the penis. The suspensory ligament is incised, and the penis is detached from the pubic bone. The deep dorsal vein is resected to expose the hilum of the penis. The entrance of the cavernous artery to the corpus cavernosum is identified. The paired dorsal arteries and nerves, cavernous arteries and nerves, and the bulb of the corpus spongiosum are dissected off the crura. Two umbilical tapes are used to ligate the proximal portion of each crus proximal to the entrance of the cavernous artery to shut off the venous leakage.

Humans↗
PubMed1999

Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model.

Erectile dysfunction occurs frequently in humans with diabetes mellitus; the molecular basis of this phenomenon is not known. We investigated the effects of diabetes on penile erection, nitric oxide synthase and growth factors expression in an animal model. Forty male rats were divided into two groups: the experimental group (n = 30) received intraperitoneal injection of Streptozotocin (STZ) dissolved in citrate buffer to induce diabetes; ten age-matched control rats received injection of citrate buffer vehicle only. Before euthanization at eight weeks, erectile function was assessed by electrostimulation of the cavernous nerves. NADPH diaphorase staining was used to identify NOS and immunostaining technique was used to identify nNOS in the penile nerve fibers. RT-PCR was used to identify mRNA expression of nNOS, eNOS, iNOS, ER-beta, ER-alpha, NGF, IGF-I, TGF-beta 1, and AR. Western blot was used to identify nNOS, IGF-I, NGF, and TFG-beta protein expressions. In the diabetic group, there was: (1) a significant decrease in NOS containing nerve fibers in the dorsal and intracavernosal nerves; (2) a significant lower maximal intracavernosal pressure. RT-PCR showed down-regulation of nNOS (large form), iNOS and ER-beta mRNA expression, Immunoblot showed down-regulation of nNOS protein expression and nNOS immunostaining showed less positive staining in the dorsal and intracavernous nerves in the diabetic group. These molecular changes may provide the basis for further studies to explore the association between diabetes and impotence.

Animals↗
PubMed1999

IGF-I and TGF-beta2 have a key role on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in rats.

The molecular mechanism of nitric oxide synthase (NOS)-containing nerve regeneration is still unknown. It is believed that growth factors are involved in this phenomenon. We investigated the change of NOS containing nerve fibers and the mRNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, TGF-beta3, vascular endothelial growth factor (VEGF), endothelial NOS (eNOS) and neuronal NOS (nNOS) on the penis after cavernous nerve neurotomy in rats. Male rats were divided into four groups: (1) sham operation (n = 14); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (n = 21); (3) unilateral neurotomy with growth hormone (n = 14); and (4) bilateral neurotomy (n = 21). Electrostimulation of the intact cavernous nerve or pelvic ganglion were performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and immunohistochemistry were used to identify NOS in the penis. The gene expression for growth factors, eNOS and nNOS were investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). One month after neurotomy, both unilateral and bilateral neurotomy groups showed significant decreases in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy. Significantly lower mRNA expression of nNOS, IGF-I and TGF-beta2, higher mRNA expression of eNOS and VEGF189 were shown in these groups. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly, while the GH-treated group showed a significant increase. At six months, those in the intracavernosal nerve only increased in a significant amount (P < 0.0001), however mRNA expression of nNOS, IGF-I and TGF-beta2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derived from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta2 may play a key role in the regeneration of nNOS-containing nerve fibers in the dorsal and intracavernosal nerves, and eNOS increases temporarily in the intracavernous involving VEGF189 after unilateral cavernous nerve injury.

Animals↗
PubMed1999

Differential gene expression of growth factors in young and old rat penile tissues is associated with erectile dysfunction.

The molecular mechanisms of erectile dysfunction with aging are unclear. Recent studies have suggested that growth factors may play a role in the etiology of erectile dysfunction. This present study was designed to test the hypothesis that gene expression of various growth factors such as TGF alpha, TGF beta 1, TGF beta 2, TGF beta 3, IGF and NGF modulate with aging in rat penile tissues. For this purpose, total RNA was extracted from young and old rat penile tissues and the gene expression for these growth factors was determined by differential reverse-transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. mRNA levels of growth factors were quantified by using beta-actin as an internal standard. The results of these experiments suggest that: (1) young and old rat penile tissues expressed mRNA transcripts for TGF alpha, TGF beta 1, TGF beta 2, TGF beta 3, IGF and NGF; (2) TGF beta 1 gene expression was significantly increased in old rat penile tissues as compared to young; (3) mRNA transcripts for NGF and TGF beta 3 were significantly lower in old rat penile tissues as compared to young; and (4) TGF alpha, TGF beta 2 and IGF mRNA expression did not change in young and old rat penile tissues. These results suggest that the differential gene expression for various growth factors in young and old rat penile tissues may be important in understanding the pathophysiology of erectile dysfunction associated with aging.

Aging↗
PubMed1999

Differential regulation of human T-plastin gene in leukocytes and non-leukocytes: identification of the promoter, enhancer, and CpG island.

Plastins (fimbrins) are a family of actin-bundling proteins conserved from yeast to humans. In humans, three tissue-specific plastin isoforms have been identified. The T isoform (T-plastin) is unique in that it is expressed in all tissues except leukocytes. To investigate how the T-plastin gene is differentially regulated in leukocytes and non-leukocytes, we isolated a genomic clone that included 9 kb of the upstream flanking region, 0.1 kb of the first exon, and 5.9 kb of the first intron. From this clone, we obtained a continuous sequence of 5535 bp, including 3138 bp of the upstream flanking region, the first exon, and 2286 bp of the first intron. A cluster of four transcription initiation sites was located by S1 mapping. A region spanning these sites and extending 1.4 kb into the first intron had the characteristics of a CpG island. Three CG-containing restriction sites within this island were analyzed and found all or variably methylated in four T-plastin-negative leukemia cell lines. In contrast, the same sites were not methylated in three T-plastin-expressing cell lines or in a sample of normal blood lymphocytes. A basal promoter was located 250 bp upstream from the transciption initiation sites. It comprised a CCAAT box, an Sp1 motif, and four AP2 motifs. No TATA or Inr sequence was found. The basal promoter exhibited weak activity when assayed in fibrosarcoma cells. Stronger promoter activities were found in the presence of the SV40 enhancer or a T-plastin enhancer located some 500 bp from the basal promoter. In T-plastin-negative leukemia cells, the T-plastin basal promoter could be activated by the SV40 enhancer but not by the T-plastin enhancer. DNA footprinting identified the T-plastin enhancer as two inverted symmetric octamers (AGATAACCTC and GAGGTCAGCT) separated by 17 nucleotides.

Base Sequence↗
PubMed1999

Lengthening shortened penis caused by Peyronie's disease using circular venous grafting and daily stretching with a vacuum erection device.

PURPOSE: We evaluated the results of chronic intermittent stretching with a vacuum erection device after circumferential tunical incision and circular venous grafting in 4 patients with penile shortening from severe Peyronie's disease. MATERIALS AND METHODS: We performed complete circumferential tunical incision and covered the defect with a circular venous graft in 4 patients with shortened penis as a result of Peyronie's disease. Preoperative evaluation included determination of patient and partner expectations, potency status, measurement of penile length after intracavernous injection and color duplex ultrasonography to determine possible vascular communication. Lower saphenous, upper saphenous and deep dorsal veins served as graft materials. We advised patients to use a vacuum device on a daily basis for 6 months starting 1 month after surgery. Postoperative evaluations were done at 6 and 18 months postoperatively. RESULTS: At 6-month followup 1 patient who did not use the vacuum device gained 1 inch in penile length and was not available for further followup. The other 3 patients each gained 2 inches but had decreased erectile rigidity due to narrowing in the grafted area (hourglass deformity). One patient who wanted a more natural erection elected penile prosthesis implantation about 1 year after grafting. The remaining 2 patients gained 3 inches at 18-month followup and regained partial penile rigidity similar to preoperative erections when the hourglass deformity improved. All patients were satisfied and indicated that surgery improved psychological well-being as well as relationships with partners. CONCLUSIONS: The results in this small group are satisfactory. Our technique offers a reasonable solution for correction of penile shortening in patients with Peyronie's disease.

Adult↗
PubMed1999

The effects of colchicine on a Peyronie's-like condition in an animal model.

PURPOSE: We have developed an animal model of Peyronie's disease by injecting transforming growth factor beta (TGF-beta) into the rat penis. Our objective is to study the effects of colchicine on the Peyronie's condition in an animal model. MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats received TGF-beta injections into the tunica albuginea and were divided into two groups (n = 18 each). Rats in the first group were divided into three subgroups (n = 6 each). Each rat in the three subgroups received the following: Subgroup 1 received colchicine, subgroup 2 received ibuprofen, and subgroup 3 received regular water. The rats were euthanized after 6 weeks. Rats in the second group were also divided into three subgroups. These rats received the same treatments as the rats in the first group, but treatments began 6 weeks after TGF-beta injection. These rats were euthanized after 12 weeks. Tunical tissue samples were collected and examined using Hart and trichrome stains, electron microscopy (EM), and western blot analysis for TGF-beta detection. RESULTS: In the first group, the colchicine-treated rats exhibited less collagen deposition and less elastic fiber fragmentation than the untreated or ibuprofen-treated rats. EM confirmed the results and showed normal distribution and shape of both collagen and elastic fibers in the colchicine-treated group. In the second group, the colchicine-treated rats exhibited less crowding of the collagen fibers. However, the elastic fibers remained fragmented and scarce. Western blot analysis showed significant down-regulation of TGF-beta expression (5/6) in the colchicine-treated group after 6 weeks. Down-regulation was observed in only 1/6 in both ibuprofen and non-treated groups. After 12 weeks 2/6, 1/6, and 1/6 rats displayed down regulation in the colchicine treated, ibuprofen treated, and non-treated groups, respectively. CONCLUSION: Early colchicine treatment may suppress a Peyronie's like condition in the rat animal model.

Animals↗
PubMed1999

Topical and oral agents for erectile dysfunction.

Innovative research in the past 2 decades has shown that the hemodynamics of penile erection involve arterial dilation, sinusoidal expansion, and venous compression. Relaxation of the intracorporeal smooth muscles (trabecular and arteriolar) seems to be the final common pathway that leads to the above events. Neuropharmacologic studies have also established nitric oxide as the principal neurotransmitter for penile erection and confirmed the importance of cyclic adenosine monophosphate and cyclic guanosine monophosphate systems in penile smooth muscle relaxation. Recent years have also witnessed dramatic changes in the therapy of erectile dysfunction. The penile prosthesis, a gold standard of therapy of the 1970s, was replaced in the 1980s by the intracavernous injection and the vacuum constriction device. In the 1990s, two revolutionary concepts in erectile dysfunction therapy were added: transurethral alprostadil and oral sildenafil. However, the tremendous publicity surrounding the recent introduction of sildenafil has also created socioeconomic and ethical dilemmas, especially with regard to insurance coverage and government regulation. Medically, many problems also surfaced when large numbers of erectile dysfunction patients overwhelmed primary care physicians who were unfamiliar with the diagnosis and treatment of erectile dysfunction. This article reviews the advances in penile physiology and the clinical usefulness of topical and oral agents. In addition, a patients' goal-directed approach to the diagnosis and treatment of erectile dysfunction is presented.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Analysis of neuronal nitric oxide synthase isoform expression and identification of human nNOS-mu.

The neuronal form of nitric oxide synthase (nNOS) is responsible for the production of NO, which acts as a neurotransmitter for penile erection and urethra relaxation. An nNOS splice variant form, nNOS-mu, was first reported to be specifically expressed in skeletal muscle and heart in the rat, but later also identified in rat penile cavernosum. We report here an apparently universal expression of nNOS-mu mRNA in rat tissues, including brain, which was previously reported to be lacking nNOS-mu. Immunoblot analysis revealed that some commercially available nNOS antibodies had high levels of nonspecific activities, which could lead to the appearance of seemingly multiple forms of nNOS. Immunohistochemical analysis with these antibodies also produced nonspecific stainings. In humans, nNOS-mu; expression appeared to be confined to skeletal muscle and heart. Human penile tissues obtained from patients with erectile dysfunction did not express nNOS-mu. The human nNOS-mu-specific cDNA sequence was 89% homologous to its rat counterpart.

Alternative Splicing↗
PubMed1998

Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group.

BACKGROUND: Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [corrected] in the corpus cavernosum and therefore increases the penile response to sexual stimulation. We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, and mixed causes. METHODS: In a 24-week dose-response study, 532 men were treated with oral sildenafil (25, 50, or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329 different men were treated with sildenafil or placebo, with dose escalation to 100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of the 329 men entered a 32-week, open-label extension study. We assessed efficacy according to the International Index of Erectile Function, a patient log, and a global-efficacy question. RESULTS: In the dose-response study, increasing doses of sildenafil were associated with improved erectile function (P values for increases in scores for questions about achieving and maintaining erections were <0.001). For the men receiving 100 mg of sildenafil, the mean score for the question about achieving erections was 100 percent higher after treatment than at base line (4.0 vs. 2.0 of a possible score of 5). In the last four weeks of treatment in the dose-escalation study, 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil, as compared with 22 percent for those receiving placebo (P<0.001). The mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo (P<0.001). Headache, flushing, and dyspepsia were the most common adverse effects in the dose-escalation study, occurring in 6 percent to 18 percent of the men. Ninety-two percent of the men completed the 32-week extension study. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Continence mechanism of the ileal neobladder in women: a urodynamics study.

We undertook this study to evaluate the mechanism of continence in women who underwent modified radical cystectomy and creation of an ileal neobladder. Our surgical technique was modified in accordance with detailed anatomic dissection of female pelvises with attention to the innervation of the pelvic musculature and urethral sphincter. Ten women aged 41-71 years (mean 64.3 years) underwent nerve-sparing radical cystectomy and creation of an orthotopic neobladder with detubularized ileum. Videourodynamic evaluation was performed 6 months postoperatively to evaluate sphincteric and reservoir function. Seven of the ten patients were totally continent after the procedure, requiring no protective pad. Of these, one requires intermittent self-catheterization. Videourodynamic evaluation revealed a low-pressure reservoir with a mean capacity of 467 ml, and leakage did not occur during Valsalva maneuver. Three patients reported significant incontinence (more than one pad per day) after orthotopic reconstruction. These patients demonstrated intrinsic sphincteric deficiency with a low mean abdominal leak-point pressure of 48.3 cmH2O. Two of these women had stress incontinence preoperatively. In conclusion, continence can be preserved in most women after modified radical cystectomy and orthotopic bladder replacement. Success results from preservation of the intrinsic sphincteric mechanism and the creation of a low-pressure, compliant reservoir. A history of stress incontinence preoperatively appears to predispose to sphincteric weakness postoperatively.

Adult↗