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Biomedical subjects

T C Park

Publications and source records attributed to T C Park.

10 recordsLinked to original sources
PubMed1997

Role of nitric oxide in penile erection.

The present study was undertaken to investigate the role of nitric oxide (NO) in erectile physiology by correlating its action with the existence and activity of nitric oxide synthase (NOS), which produces NO. We applied Western blot analysis in both human and rat penile tissue. In the rat, reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and spectrophotometric assay were also performed, in addition to in vivo electroerection study with pharmacological manipulation. Western blot analysis identified a protein of 155 KDa identical to the neural form of NOS in the human and rat penis. The NOS blot densities in the two species were similar, and both were lower than that in the rat cerebellum. Histochemical staining localized NOS to neurons innervating the corpora cavernosa, including the pelvic plexus, the cavernosal nerves and their terminal fibers within the corporeal erectile tissue, and dorsal penile nerves. NOS activity was also found in the cerebellum, urethra, penis, and urinary bladder, in decreasing order of intensity. Intracavernous injections of NOS inhibitor (L-NOARG or L-NAME in concentrations from 10(-6) M to 10(-3) M suppressed electrostimulation-induced erection in a concentration-dependent manner. Subsequent intracavernous injection of L-Arginine (10(-2) M) partially restored the erection. The neural form of constitutive NOS in the corpora cavernosa synthesizes NO, which mediates penile erection. Determination of cavernosal NOS expression or activity may permit characterization of certain pathological conditions that cause impotence.

Animals↗
PubMed1996

Effects of site-directed mutagenesis of basic residues (Arg 94, Lys 95, Lys 99) of lipopolysaccharide (LPS)-binding protein on binding and transfer of LPS and subsequent immune cell activation.

LPS-binding protein (LBP) is a 60-kDa acute phase glycoprotein capable of binding the LPS of Gram-negative bacteria and facilitating its diffusion. This process is thought to be of potential importance in inflammatory reactions and pathogenic states such as septic shock syndrome. Here, we report on the identification of a LPS binding domain within the LBP molecule and on the identification of single amino acids important for binding of LPS by LBP. Several synthetic LBP peptides inhibited LPS-LBP interaction, and amino acids Arg 94 and Lys 95 were centrally located in these inhibitory peptides. LBP mutants with amino acid exchanges within this region were expressed and tested in five different functional assays: binding to immobilized LPS; facilitation of binding of LPS aggregates to monocytes; transfer of LPS monomers from aggregates to soluble CD14; transfer of soluble CD14-bound LPS monomers to high density lipoprotein (HDL); and enhancement of LPS-induced cell activation. The double mutant Glu 94/Glu 95 was completely lacking LPS binding, transfer, and cell stimulatory activity, indicating that the integrity of amino acids 94 and 95 is required for LBP function. While mutations of amino acids Arg 94 or Lys 95 into alanine reduced the LPS binding activity of LBP dramatically, the ability to facilitate binding of LPS aggregates to membrane CD14 at the cell surface was retained. These findings emphasize the distinction between binding of LPS aggregates to cells, which is not associated with cell stimulation, and binding of LPS monomers to CD14, which leads to cell stimulation.

Acute-Phase Proteins↗
PubMed1996

CUMC-6, a new diploid human cell line derived from a squamous carcinoma of the uterine cervix.

A new cell line, CUMC-6, has been derived from an invasive nonkeratinizing squamous cell carcinoma of the uterine cervix in a 31-year-old patient. It has been maintained in long-term culture for 61 months, and passaged over 300 times. Monolayer-cultured cells were polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. The epithelial nature of the cultured CUMC-6 cells was confirmed by transmission electron microscopy which demonstrated the presence of desmosomes and tonofilaments. The subcutaneous injection of cultured cells into nude mice gave rise to fast-growing tumors. The transplanted tumor showed similar histological features, but poor differentiation compared to the original tumor. Cultured CUMC-6 cells produced human chorionic gonadotropin beta-subunit (beta-HCG) and alpha-fetoprotein (AFP). Cytosol estrogen and progesterone receptors were not measured in this cell line. The results of isozyme analyses were distinct from the HeLa cell line. Repeated chromosome analysis from passage 6 to 300 revealed that most metaphases of this cell line contained diploid number of chromosomes. The structural abnormality consistently observed in this cell line was the elongation of short arm of chromosome 1. The G- or R-banded pattern of this chromosome suggested inv dup (1) (1pter-->1p34[symbol: see text] 1p21-->1p34[symbol: see text] 1p34-->1qter). Human leukocyte antigen (HLA) typing of CUMC-6 cells indicated the presence of DR12 and DQw3. Analysis of the DNA extracted from the CUMC-6 cells showed the presence of human papillomavirus (HPV) type 16 and 18 DNAs. The results of oncogene analyses using Southern blotting technique revealed amplification and rearrangement of oncogene c-myc and no amplification of oncogene L-myc. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, we have screened CUMC-6 cells for p53 mutation in exons 4 to 9. No mobility shift was observed in this cell line. These results suggest that chromosome 1 abnormality, oncogene alteration, and HPV infection work together in cervical tumorigenesis.

Animals↗
PubMed1995

Aberrations of the p53 tumor suppressor gene in human epithelial ovarian carcinoma.

Aberrations of the p53 gene in 26 surgical specimens of human epithelial ovarian carcinomas were examined by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products. Seven (27%) of the tumors demonstrated a SSCP band shift in exons 4 to 9 of the gene, including 5 in the region encompassing exons 5 and 6, 1 in exon 7, and 1 in the region encompassing exons 8 and 9. Mutations were clustered in exon 5 in highly conserved regions of the p53 gene. All of the abnormal DNA fragments have been further characterized by direct DNA sequencing. These include five missense mutations (five transitions), a one-base-pair deletion introducing, by frameshift, a stop codon further downstream, and a two-base-pair insertion introducing a stop codon downstream by frameshift. Most mutations were base substitutions, and were clustered in exon 5 (71%), especially codons 175 and 179. The aberrations of the p53 gene were only found in tumors of FIGO stages III and IV. Histologic grading was also reviewed with respect to p53 aberrations. The aberrations were absent in well-differentiated carcinomas. The more undifferentiated the primary tumor, the more frequent p53 mutation (P < 0.05). Our results indicated that the aberrations of the p53 gene were common in epithelial ovarian cancers and p53 aberration may occur late during ovarian cancer evolution.

Base Sequence↗
PubMed1995

Effect of vasoactive intestinal peptide and acetylcholine on penile erection in the rat in vivo.

We investigated the effect of vasoactive intestinal peptide (VIP) and its combination with acetylcholine (ACh) on the erectile response in 52 adults rats. Intracavernous injection of VIP (10(-8) to 10(-5)M, ACh (10(-9) to 10(-5), or a combination of VIP (10(-7) to 10(-5) with ACh (10(-6 M) additively enhanced that erection but did not lead to a full erection. VIP-antagonist (10(-9) to 10(-5 M), as well as atropine alone (10 (-7) to 10(-5 M), partially suppressed full erection induced by cavernous nerve stimulation (1 Hz, 3-6 V) in a dose-dependent manner, and the combination of VIP-antagonist (10(-9) to 10(-5 M) with atropine (10(-6 M) showed an additive effect. The results indicate that although VIP as well as ACh in involved in penile erection, they are not likely to be principal neurotransmitters. Their clinical application in the treatment of impotence may be confined to use in conjunction with another vasoactive agent.

Acetylcholine↗
PubMed1994

Isolated bypass to the superior mesenteric artery for intestinal ischemia.

OBJECTIVE: A number of reports indicate revascularization for intestinal ischemia should include the superior mesenteric artery (SMA) and the celiac artery. However, no controlled or randomized studies have proven this approach superior to SMA bypass alone. We report our results using bypass to only the SMA for intestinal ischemia. DESIGN: Retrospective review with mean follow-up of 40 months (range, 2 to 110 months). SETTING: University medical center and Veterans Affairs hospital. PATIENTS/METHODS: The records of patients who underwent intestinal revascularization of the SMA alone from 1982 through 1993 were reviewed. Patients were assessed for indication for operation, operative technique, perioperative mortality, and long-term outcome. The SMA grafts were examined for patency within the last 6 months using duplex scanning or arteriography. Patient survival and graft patency rates were calculated using life-table methods. RESULTS: Twenty-nine bypasses to only the SMA were performed in 26 patients (16 female and 10 male; mean age, 59 years; age range, 13 to 81 years). Indication for operation was symptomatic chronic mesenteric ischemia in 23 cases and acute intestinal ischemia in five cases. One bypass was performed for asymptomatic SMA occlusion. There were three perioperative deaths (10% mortality rate), all in patients with acute intestinal ischemia and previous mesenteric arterial surgery. Life-table 4-year primary graft patency and patient survival rates were 89% and 82%, respectively. Symptomatic improvement was maintained in all patients available for follow-up. CONCLUSION: Revascularization of only the SMA for intestinal ischemia provides excellent graft patency with acceptable perioperative mortality and long-term patient survival. The SMA bypass alone for intestinal ischemia appears as successful as bypasses to multiple visceral vessels.

Adolescent↗
PubMed1994

Acute disruption of polytetrafluoroethylene grafts adjacent to axillary anastomoses: a complication of axillofemoral grafting.

PURPOSE: Acute disruption at or adjacent to axillary anastomoses of axillofemoral grafts has been sporadically reported. We have recently reported the patency and limb salvage results of a large number of axillofemoral grafts. In this report we describe a series of axillary artery-graft disruptions that occurred in these patients. METHODS: Beginning in 1983, axillofemoral bypass was performed by the authors using standardized operative technique and a single prosthetic graft material (8 mm externally supported polytetrafluoroethylene). Axillary anastomoses were placed on the first portion of the artery and were performed with the arm abducted and with the graft redundant. The records and operative reports of all patients with disruption were reviewed for findings and subsequent hospital course. RESULTS: Two hundred two axillofemoral grafts were performed from 1983 to 1993. Ten patients (5%) had axillary disruption at intervals ranging from 1 to 46 days (mean 21 days) after operation. Ischemia was the indication for operation for seven of the patients and infected aortic prostheses for three. Infection did not occur in any of the axillary wounds and was not the cause of any of the disruptions. Four disruptions occurred with arm abduction/shoulder elevation movements; three awakened patients from sleep, and one occurred while the patient was sitting quietly. For the other two patients, preceding activity was unknown. Brachial plexus deficit was present in one patient. Four of the 10 disrupted grafts were also acutely occluded. Operative findings included sutures pulling out of the artery in four cases, tearing or sutures pulling out of the graft in four cases, and cause unknown in two cases. Treatment included arterial ligation in one patient, and restoration of circulation through revision of the axillofemoral grafts in the other nine patients. There were no operative deaths. One patient had a prolonged hospital course followed by nursing home placement and died 9 months later. The brachial plexus deficit did not resolve. There have been no repeat disruptions. CONCLUSIONS: We conclude that axillofemoral grafting includes the potential for disruption of the proximal anastomosis, which has occurred in 5% of our patients. Although multiple steps have been recommended to avoid this complication, occasional cases continue to occur despite observing all precautions.

Acute Disease↗
PubMed1993

Human saphenous vein grafts explanted from the arterial circulation demonstrate altered smooth-muscle and endothelial responses.

PURPOSE: Animal models have been used to assess the function of vascular smooth muscle and endothelium of veins grafted into arterial circulation. The primary model consists of grafting the external jugular vein into the carotid artery of the rabbit. These studies suggest a selective increase in the responsiveness of the grafted veins to serotonin. However, in both human cardiac and peripheral vascular operations, the saphenous, not the jugular, is the vein most frequently used. Thus the propriety of the rabbit model is unknown. METHODS: Human saphenous veins and vein grafts were obtained from patients undergoing leg vein bypass graft revisions (n = 8). The reversed vein grafts were placed into arterial circulation for periods ranging from 4 to 26 months before removal (mean 16 months). All vessels were immediately cut into rings and suspended in organ chambers for recording isometric contractions to norepinephrine and serotonin. RESULTS: The maximal contractions elicited by both norepinephrine and serotonin were reduced in human vein grafts in comparison to the results in human saphenous vein (maximal response to norepinephrine 1.42 +/- 0.34 gm [vein graft] vs 4.59 +/- 1.13 gm [saphenous vein], p = 0.031; maximal response to serotonin 2.68 +/- 0.58 gm [vein graft] vs 4.72 +/- 1.11 gm [saphenous vein], p = 0.042). Human vein grafts were less responsive to norepinephrine than was saphenous vein (negative log of concentration that caused 50% of the maximal response -5.91 +/- 0.10 and -6.84 +/- 0.22, respectively; p < 0.009). After precontraction with norepinephrine (to 30% of the maximal response), saphenous vein, but not vein grafts, demonstrated endothelium-dependent relaxation to acetylcholine (maximum relaxation 27.4% +/- 6.8%; p = 0.001). CONCLUSIONS: Human saphenous veins grafted into arterial circulation exhibit loss of endothelium-dependent relaxation to acetylcholine and diminished contractions to agonists (norepinephrine and serotonin). In contrast to rabbit data, serotonin elicits dose-dependent contractions in both human saphenous vein and human vein grafts. Since the vascular wall contractility varies widely across species, the relevance of rabbit vein graft data to human bypass grafts is uncertain.

Acetylcholine↗