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Biomedical subjects

Tom F Lue

Publications and source records attributed to Tom F Lue.

63 records · Page 4Linked to original sources

[Studies on the testis regression related gene profile in aged male].

OBJECTIVE: To understand the mechanism of testis regression in aging male. METHODS: Human testis tissues were obtained during related operation with informed consent (normal young male 3 cases and aged male 3 cases). Total RNA was isolated by QIAGEN RNAeasy kit. Differentiations of gene expression were studied by Clon-Tech cDNA microarray methods and the differential expression gene in aged male were classified by Venter's classify system and the candidate genes were investigated by RT-PCR analysis. RESULTS: In the results of cDNA microarray we found 117(1.46%) gene differentiations in aged male at least more than 1.0 fold. Among them, the 83 genes were down-regulated and the 34 genes up-regulated. The down expressed genes related to metabolism were 16(19.3%), gene or protein expression 18(21.7%), cell signaling or cell communication 16(19.3%), cell division 19(22.9%), cell structure or motility 6(7.2%) and unknown function 4 genes (4.8%). The up expressed genes related to cell division were 11 (32.4%), gene or protein expression 10(29.4%) and metabolism 3 (8.8%). It is interesting to find that respiratory chain related gene cox7a2 was up-regulated and atp50 down-regulated significantly which as further confirmed by RT-PCR analysis with sequence analysis in the products of the RT-PCR by T-A cloning. CONCLUSION: The gene expression profile in aged male testis was changed significantly as compared with that in normal young controls; testis regression in aging male may relate multi-gene differentiations, especially the differentiations of respiratory chain related gene cox7a2, atp50, which may be an important candidate gene in the study of the mechanism of testis regression in aging male.

Cell Differentiation↗

Upregulation of monocyte chemoattractant protein 1 and effects of transforming growth factor-beta 1 in Peyronie's disease.

Peyronie's disease (PD) is characterized by fibrosis in the tunica albuginea (TA) of the penis, which becomes bent as a result. We have previously shown that transforming growth factor-beta 1 (TGF-beta1) is upregulated in the TA of patients with PD and can initiate PD-like lesions in rat models. In this study we isolated three types of fibroblasts: P cells from the lesions of PD patients, C cells from the normal-appearing areas of the TA of the same patients, and N cells from the TA of patients without PD. We examined these cells for the expression of two fibrogenic cytokines, connective tissue growth factor (CTGF), and Monocyte Chemoattractant Protein 1 (MCP-1). We found that CTGF was expressed at similar levels in P, C, and N cells, whereas MCP-1 was significantly more expressed in P cells than in C cells and more in C cells than in N cells. Higher MCP-1 expression was also found in the lesions than in normal TA. Treatment with TGF-beta1-induced higher expression of MCP-1 but not CTGF in all three types of cells, with C cells being the most responsive. Based on these observations, we propose that MCP-1 could be a novel therapeutic target in PD.

Chemokine CCL2↗

Vascular endothelial growth factor induces IP-10 chemokine expression.

We have previously shown that intracavernous injection of vascular endothelial growth factor (VEGF) improved the recovery of erectile function in an arteriogenic impotence rat mode. We wished to identify genes that are affected by VEGF treatment in the penis. Specifically we examined the induction of IP-10 chemokine. Male rats were subjected to pudendal arterial ligation or sham operation. They were then treated with intracavernous injection of 4 microg of VEGF in phosphate-buffered saline (PBS) or PBS alone. At 6 and 24 h after treatment, the erectile tissue was then harvested for RNA isolation. The isolated RNA was used for microarray and RT-PCR analyses. Cultured rat cavernous smooth muscle cells (CSMC) were treated with VEGF and then subjected to RT-PCR analysis. Cultured human CSMC were treated with VEGF and then subjected to ELISA analysis. Microarray analysis detected IP-10 as an abundantly induced message in 6-h VEGF-treated tissues. This was further confirmed by RT-PCR analysis. Using cultured rat CSMC, induction of IP-10 mRNA was detectable in 1 and 2 h, but not 24 h, VEGF-treated cells. Induction of IP-10 at the protein level was observed with cultured human CSMC. Secretion of IP-10 into culture medium peaked at 4 h after treatment of human CSMC with 10 ng/ml of VEGF. Optimal VEGF dosage for IP-10 induction was 50 ng/ml when assayed with cells that were treated for 8 h.

Animals↗

The effect of vascular endothelial growth factor on a rat model of traumatic arteriogenic erectile dysfunction.

PURPOSE: We tested the hypothesis that intracavernous injection of vascular endothelial growth factor (VEGF) can restore erectile function in a rat model of traumatic arteriogenic erectile dysfunction. MATERIALS AND METHODS: Exploration of bilateral internal iliac arteries was performed in 50, 3-month-old male rats. A total of 44 rats underwent bilateral ligation of the internal iliac arteries and 6 that underwent exploration only served as the sham operated group. Minutes later intracavernous injection of phosphate buffered saline (PBS) plus bovine serum albumin in 16 rats, 2 microg. VEGF plus PBS plus BSA in 12 and 4 microg. VEGF plus PBS plus BSA in 16 was performed. At weeks 1, 2 and 6 about a third of the rats in each group underwent electrostimulation of the cavernous nerves to assess erectile function and were then sacrificed. Penile tissues were collected for histochemical and electron microscopy examinations. RESULTS: No impairment of erectile function was noted in sham operated rats. Immediately after arterial ligation all rats showed little or no erectile response to neurostimulation. In PBS treated rats modest recovery of erectile function was noted at week 6. Significant recovery of erectile function was noted in VEGF treated rats at weeks 1 and 2 in the 4 microg. group only and at week 6 in the 2 and 4 microg. groups. Neuronal nitric oxide synthase staining showed a reduction in neuronal nitric oxide synthase positive nerve fibers in the dorsal or intracavernous nerves at week 1. Moderate recovery of neuronal nitric oxide synthase positive nerve fibers was noted in the 2 and 4microg. VEGF treated groups but not in the PBS treated group. Electron microscopy revealed no pathological change in sham operated rats. In dorsal nerves the atrophy of myelinated and nonmyelinated nerve fibers was noted in ligated plus PBS treated rats. Partial recovery was observed in VEGF treated rats. Scattered atrophic smooth muscle cells were seen in PBS and occasionally in VEGF treated rats but not in the sham operated group. The most dramatic findings in VEGF treated rats were hypertrophy and hyperplasia of the endothelial cells, especially those lining the small capillaries. CONCLUSIONS: Ligation of bilateral internal iliac arteries produced a reliable animal model of traumatic arteriogenic erectile dysfunction. Intracavernous injection of VEGF minutes after arterial ligation facilitated the recovery of erectile function.

Animals↗

Psychological impact of erectile dysfunction: validation of a new health related quality of life measure for patients with erectile dysfunction.

PURPOSE: Male erectile dysfunction has a substantial impact on health related quality of life. We examined the psychometric properties of 2 new scales created to measure the psychological impact of erectile dysfunction. MATERIALS AND METHODS: Patients enrolled in a long-term study of men with erectile dysfunction completed clinical and health related quality of life information at baseline and at 3 followup points. The questionnaire incorporated a number of standard scales of psychosocial characteristics as well as questions developed from comments made during focus groups of men with erectile dysfunction and of their female partners. Principal components analysis was used to identify underlying constructs in response to the new questions. RESULTS: A total of 168 men completed the baseline quality of life questionnaire. The principal components analysis of the psychological impact of erectile dysfunction questions resulted in 2 new scales. Reliability was good with an internal consistency reliability of 0.91 for scale 1 and 0.72 for scale 2. Test-retest reliability was 0.76 and 0.66, respectively. Men reporting a greater psychological impact of erectile dysfunction also reported greater impairment in functional status, lower sexual self-efficacy, greater depression and anxiety at the last intercourse. Each new scale significantly differentiated men with mild/moderate versus severe erectile dysfunction. CONCLUSIONS: We developed 2 new scales to measure the psychological impact of erectile dysfunction and they showed good reliability and validity. These new scales, named the Psychological Impact of Erectile Dysfunction instrument, comprehensively capture the psychological effect of erectile dysfunction on health related quality of life, which is not adequately assessed by existing patient centered measures of erectile function.

Adult↗

Brain activation and sexual arousal in healthy, heterosexual males.

Despite the brain's central role in sexual function, little is known about relationships between brain activation and sexual response. In this study, we employed functional MRI (fMRI) to examine relationships between brain activation and sexual arousal in a group of young, healthy, heterosexual males. Each subject was exposed to two sequences of video material consisting of explicitly erotic (E), relaxing (R) and sports (S) segments in an unpredictable order. Data on penile turgidity was collected using a custom-built pneumatic pressure cuff. Both traditional block analyses using contrasts between sexually arousing and non-arousing video clips and a regression using penile turgidity as the covariate of interest were performed. In both types of analyses, contrast images were computed for each subject and these images were subsequently used in a random effects analysis. Strong activations specifically associated with penile turgidity were observed in the right subinsular region including the claustrum, left caudate and putamen, right middle occipital/ middle temporal gyri, bilateral cingulate gyrus and right sensorimotor and pre-motor regions. Smaller, but significant activation was observed in the right hypothalamus. Few significant activations were found in the block analyses. Implications of the findings are discussed. Our study demonstrates the feasibility of examining brain activation/sexual response relationships in an fMRI environment and reveals a number of brain structures whose activation is time-locked to sexual arousal.

Adolescent↗

Correction of penile curvature using the 16-dot plication technique: a review of 132 patients.

PURPOSE: We review the results of 132 cases of congenital and acquired penile curvature corrected with our 16 or 24-dot, minimal tension technique using multiple parallel plications performed under papaverine induced erection. MATERIALS AND METHODS: Chart and telephone interviews were conducted on 132 consecutive patients 16 to 79 years old who underwent penile plication between December 1995 and November 2000. Patient data as well as outcomes were analyzed. RESULTS: We were unable to contact 8 patients. Of the patients 16 had congenital penile curvature, including 4 in whom the Nesbit procedure performed elsewhere had failed, and 116 had Peyronie's disease, including 8 in whom a previous Nesbit procedure had failed. Preoperative complaints included persistent penile pain with erection for more than 1 year in 15 of 132 cases, difficult intercourse or partner discomfort in 106 and poor self-image in 11. Curvature ranged from 30 to 120 degrees. Erections were evaluated preoperatively with duplex ultrasound after intracavernous injection and self-stimulation. Of the patients 63% had good erections, 25% moderate erections requiring sildenafil and 12% poor erections requiring injection therapy. Foreskin edema necessitating subsequent circumcision and an organized hematoma requiring evacuation occurred in 1 case each. At 6 months 93% of patients reported straight erections and 7% reported almost straight but acceptable erections. Recurrence of curvature was reported by 15% of patients at a mean of 2.6 years of followup. Four patients reported worsening of erectile function after the procedure. CONCLUSIONS: Penile plication is a simple, safe method to correct congenital and acquired penile curvature. Using a minimal tension parallel plication technique, excellent durable results can be attained. This simplified repair avoids the neurovascular bundles and has a minimal to no detrimental affect on erectile function. Preoperative counseling must be given regarding penile shortening and the palpable small bumps from the nonabsorbable sutures.

Adolescent↗

Long-term effect of ovariectomy and simulated birth trauma on the lower urinary tract of female rats.

PURPOSE: Using an animal model we studied the long-term effects of ovariectomy and simulated birth trauma in the development of apoptosis as well as the urodynamic, histological and ultrastructural findings 9 months after such procedures. MATERIALS AND METHODS: A total of 24 pregnant Sprague-Dawley female rats were used. Immediately after delivery 14 animals underwent vaginal ballooning and ovariectomy, while the remaining 10 served as controls. At 9 months the animals underwent urodynamic evaluation, which included the urethral pressure profile. The rats were then sacrificed and urogenital tissue was obtained for immunostaining using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling, histomorphometry evaluation and electron microscopy. RESULTS: Immunostaining demonstrated a significant increase in the apoptotic index in the urethra of castrated/ballooning rats with a predominance in the submucosa layer. Maximum urethral closure pressure was significantly lower in that group, although there was no correlation of apoptosis with maximum urethral closure pressure measurement. Urodynamic evaluation revealed only discrete alterations in cystometric parameters. Morphometric evaluation showed increased connective tissue in the vagina. Electron microscopy of urethral smooth muscle demonstrated altered cellular shape, increased intercellular space with collagen deposition and some degeneration of the mitochondria. CONCLUSIONS: Apoptosis in the urethra occurs 9 months after castration and simulated birth trauma. However, this finding was not seen in the muscle layers or in other urogenital tissues. Some ultrastructural changes also occurred that may explain some symptoms that women have after vaginal childbirth and menopause.

Animals↗