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Biomedical subjects

S E Wilson

Publications and source records attributed to S E Wilson.

At least 91 records · Page 5Linked to original sources

Novel human malignancy-associated gene (MAG) expressed in various tumors and in some tumor preexisting conditions.

We have identified a novel human malignancy-associated gene (MAG) expressed in various malignant tumors including glioblastomas and hepatocellular carcinomas (HCCs) and in tumor preexisting conditions such as hepatitis C virus- and hepatitis B virus-induced liver cirrhosis. The expression of MAG was characterized using reverse transcription-PCR (RT-PCR), rapid amplification of cDNA ends PCR, RNA dot blotting, RNase protection assay, and Northern blot analysis. Rapid amplification of cDNA ends PCR yielded a 536-bp MAG fragment in HCC, macroregenerative liver nodules with dysplasia, and liver cirrhosis but not in normal liver or placenta. By RT-PCR, MAG expression was not found in 12 different normal tissues but found in 46 of 51 (90%) premalignant and malignant tissues of various sites. Embryonic liver and brain were positive for MAG expression together with tumors from the same organs, but the corresponding normal adult tissues were negative. By RNase protection assay, MAG mRNA was expressed in the HepG2 liver tumor cell line and in an ovarian carcinoma but not in normal liver. The estimated transcript size from Northern blot analysis was 8.8 kb. This novel gene may play a role in the progression of premalignant conditions and in the development of HCC and other cancers.

Adult↗

Cross-clade envelope glycoprotein 160-specific CD8+ cytotoxic T lymphocyte responses in early HIV type 1 clade B infection.

A major objective of current HIV-1 vaccination strategies is the induction of HIV-1-specific CD8+ MHC class I-restricted CTL responses, which are suggested to play a pivotal role in viral clearance and protection against HIV-1 disease progression. However, the marked genetic diversity of HIV-1 and existence of distinct viral subtypes or clades could potentially hinder the development of a universally efficacious HIV-1 vaccine. In this study we examined HIV-1 intraclade (B(LAI) versus B(MN)) Env gp160-specific CTL reactivity in recently HIV-1 clade B-infected individuals. We further evaluated the extent of interclade CTL cross-recognition of the divergent A and C Env gp160 subtypes, that are highly prevalent in the global pandemic. Freshly isolated PBMCs were stimulated in vitro with autologous PBMCs infected with recombinant vaccinia vectors expressing HIV-1 env, gag, pol, and nef genes derived from HIV-1 clade B. All 13 of the 19 HIV-1-seropositive subjects who elicited significant clade B Env gp160LAI CD8+ CTL responses also demonstrated comparable levels of CTL cross-reactivity against clade C92BR025 Env gp160. Nine of these individuals also showed extensive interclade CTL cross-recognition of clade A92UG037 Env gp160. Two HLA class I B7 donors had nondetectable intraclade CTL response against B Env gp160MN, while generating significant intraclade B(LAI) and interclade (A and C) Env gp160 CTL cross-reactivity. These observations serve to underscore the central importance of the HLA background of individuals in determining the pattern of immune reactivity to natural HIV-1 infection and presumably vaccines. Five donors studied also demonstrated broad CTL cross-reactivity against clade A92UG037 Gag p55, Pol, and/or Nef antigens. In conclusion, this present study indicates that there is a considerable degree of CD8+ CTL cross-recognition of the highly divergent HIV-1 Env gp160 subtypes during early phases of HIV-1 infection. Such findings suggest that HIV-1 vaccines based on a single clade that can induce extensive cross-clade immunity may demonstrate utility in diverse geographical regions.

CD8-Positive T-Lymphocytes↗

Oligomeric properties and DNA binding specificities of repressor isoforms from the Streptomyces bacteriophage phiC31.

Three protein isoforms (74, 54 and 42 kDa) are expressed from repressor gene c in the Streptomyces temperate bacteriophage phiC31. Because expression of the two smaller isoforms, 54 and 42 kDa, is sufficient for superinfection immunity, the interaction between these isoforms was studied. The native 42 kDa repressor (Nat42) and an N-terminally 6x histidine-tagged 54 kDa isoform (His54) were shown by co-purification on a Ni-NTA column to interact in Streptomyces lividans . In vitro three repressor preparations, containing Nat42, His54 and the native 54 and 42 kDa isoforms expressed together (Nat54&42), were subjected to chemical crosslinking and gel filtration analysis. Homo- and hetero-tetramers were observed. Previous work showed that the smallest isoform bound to 17 bp operators containing aconservedinvertedrepeat (CIR) and that the CIRs were located at 16 loci throughout the phiC31 genome. One of the CIRs (CIR6) is believed to be critical for regulating the lytic pathway. The DNA binding activities of the three repressor preparations were studied using fragments containing CIRs (CIR3-CIR6) from the essential early region as templates for DNase I footprinting. Whereas Nat42 bound to CIR6, poorly to CIR5 but undetectably to CIR3 or CIR4, the Nat54&42 preparation could bind to all CIRs tested, albeit poorly to CIR3 and CIR4. The His54 isoform bound all CIRs tested. Isoforms expressed from the phiC31 repressor gene, like those which are expressed from many eukaryotic transcription factor genes, apparently have different binding specificities.

Bacteriophages↗

Effect of surgical panel composition on patient outcome at a level I trauma center.

OBJECTIVE: To compare the effect of staffing with general surgeons vs trauma specialists on patient outcome at a trauma center. DESIGN: The care of injured patients at a level I urban trauma center serving a population of 2.5 million was the responsibility of 12 surgeons (10 general surgeons and 2 trauma specialists) between January 1 and June 30, 1996 (group 1). Between July 1 and December 31, 1996 (group 2), trauma was the responsibility solely of 4 trauma specialists. An additional comparison was made with those patients in group 1 who were admitted to the general surgeons (group 1A). The outcomes and quality of care for these periods, as determined by the quality assurance screens, were retrospectively analyzed and compared. SETTING: Urban, tertiary care, level I trauma center. PARTICIPANTS: Each trauma and burn patient admitted during the study periods is included in this study. Upon the patient's discharge from the hospital, specially trained nurses completed a review of the patient's stay and entered it into the TraumaOne database (Lancet Technology Inc, Cambridge, Mass). There were 693 trauma patients in group 1 (472 in group 1A) and 734 patients in group 2. MAIN OUTCOME MEASURES: Mortality, length of stay, and 16 quality assurance screens were quantified and compared using chi(2) analyses and t tests. RESULTS: The age and sex of the 2 groups were similar. The mortality rate was 6.2% (43/693) in group 1, 6.1% (29/472) in group 1A, and 6.5% (48/734) in group 2 (P = .80 and P = .78, respectively). When stratified by injury severity score (ISS), lengths of stay were statistically similar, except for patients with an ISS of 0 to 7. Patients with an ISS of 0 to 7 in groups 1 and 1A stayed a mean of 2.6 days, compared with 3.2 days for group 2 (P = .01 and P = .02, respectively). The results of quality assurance screens (missed injury, wound infection, readmission, and 13 others) were similar in the 2 groups. CONCLUSIONS: Transitions in staffing afforded the opportunity to examine patient outcomes by surgeon specialization and frequency of call. In our sample, 12 well-trained surgeons taking call less frequently managed a trauma service as efficiently as a group of 4 trauma specialists, without any differences in morbidity and mortality.

Adult↗

Local treatment of prosthetic vascular graft infection with multivesicular liposome-encapsulated amikacin.

BACKGROUND: Contaminated surgical fields limit the use of prosthetic vascular grafts. We studied the efficacy of sustained-release amikacin applied locally to contaminated grafts in the prevention of infectious complications. MATERIALS AND METHODS: Thirty-one New Zealand white rabbits underwent placement of a polytetrafluoroethylene (PTFE) interposition graft in a 1-cm segment of the descending aorta. The surgical field was infected with application of 10(5) to 10(8) Staphylococcus aureus organisms suspended in normal saline solution. Nineteen rabbits underwent contaminated aortic graft placement without treatment. Twelve rabbits were treated with local application of 2.5 ml of amikacin encapsulated in lipid particle-based sustained-release dosage form. Rabbits were observed for 2 weeks and then evaluated for the presence of graft infection. RESULTS: Seventy-five percent of the treated rabbits survived without evidence of graft infection or systemic sepsis versus 37% in the untreated group (P < 0.04). Cultures verified the absence of organisms in all surviving rabbits without clinical infection. CONCLUSIONS: Sustained-release lipid particle-encapsulated amikacin applied to contaminated PTFE grafts increased survival and decreased postoperative graft infections. Adjunctive use of local, delayed-release antibiotics in contaminated vascular beds may allow wider clinical use of prosthetic grafts.

Amikacin↗

Transepithelial photorefractive keratectomy for treatment of thin flaps or caps after complicated laser in situ keratomileusis.

PURPOSE: To report transepithelial photorefractive keratectomy treatment of corneal irregularities produced during laser in situ keratomileusis (LASIK) in which there is a thin flap or cap associated with central corneal scarring or epithelial ingrowth that threatens vision. METHODS: Case reports. The thickness of the abnormal corneal flap or cap and associated scarring or epithelial ingrowth is estimated at the slit lamp or measured with an optical pachymeter. If residual myopia is sufficiently high to allow complete ablation of the flap or cap in the central cornea, a transepithelial photorefractive keratectomy is performed in which the epithelium is completely ablated with the excimer laser in phototherapeutic keratectomy mode; residual myopia is corrected using photorefractive keratectomy. RESULTS: This method was used successfully in two eyes of two patients in which a thin cap was associated with a transverse cut through the central cornea or a donut-shaped flap associated with epithelial ingrowth in the central cornea. In both cases, the abnormal cap or flap was ablated, central corneal clarity restored, and visual function improved. CONCLUSION: Transepithelial photorefractive keratectomy may be effective in treating central corneal thin cap or flap abnormalities associated with LASIK.

Adult↗

Helical CT angiography in the preoperative evaluation of carotid artery stenosis.

PURPOSE: To determine the utility and accuracy of helical CT angiography (CTA) in the evaluation of carotid artery stenosis. METHODS: A comparison of CTA and conventional arteriogram was performed in 53 patients undergoing evaluation for carotid artery stenosis. Ninety-six carotid systems were evaluable. CTA stenosis was determined by the percent of area reduction seen on axial images through the level of greatest narrowing. MIP images were used to identify the point of maximal stenosis and to visualize overall vascular anatomy. The percent diameter stenosis was measured on conventional arteriograms using strict North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) criteria. RESULTS: Significant correlation was found between CTA and arteriography (NASCET method R=0.87, ECST method R=0.87, p < 0.001). Using NASCET >60% as an indicator for disease, CTA had a sensitivity of 87%, specificity of 90%, accuracy of 89%, negative predictive value of 88%, and positive predictive value of 89%. CTA identified plaque characteristics such as ulcerations (8), occlusion (10), fatty plaques (22), calcifications (48), and fibrosis (2). CTA underestimated 2 cases of short segment stenoses because of volume averaging, but this discrepancy was detected by duplex scan. No complications or renal dysfunction occurred with CTA; 1 patient became symptomatic during arteriography, necessitating termination of the procedure. CONCLUSION: CTA is a safe, non-invasive technique that precisely measures carotid artery area reduction and highly correlates to conventional arteriography. With this new technology, the current standards for carotid artery imaging may need to be reevaluated, and the precise role for helical CTA more clearly defined.

Aged↗

LASIK: management of common complications. Laser in situ keratomileusis.

PURPOSE: To review common complications noted with LASIK. METHODS: Review of personal experience of the author with the procedure and work published in the literature. RESULTS: The most common complications of the LASIK procedure include flap irregularities, epithelium and other materials within the lamellar interface, irregular astigmatism, regular astigmatism, regression, and overcorrection. Infection is a rare but potentially serious complication. CONCLUSIONS: LASIK has impressive potential for the correction of myopia and hyperopia. Surgeons who perform the procedure must be familiar with recognition and treatment of potential complications of LASIK.

Corneal Diseases↗

Photorefractive keratectomy using the summit SVS Apex laser with or without astigmatic keratotomy.

PURPOSE: The purpose of this study was to evaluate the results of myopic photorefractive keratectomy (PRK) with or without astigmatic keratotomy (AK) for different levels of intended correction by using the SVS Apex laser. METHODS: This is a retrospective cohort study of 226 eyes that had PRK for myopia ranging from -1.0 to -7.6 diopters and 6 months of follow-up. In addition, 64 of these eyes had AK for naturally occurring or laser-induced astigmatism. Uncorrected visual acuity, spectacle-corrected visual acuity, and corneal topography with quantitative descriptors of surface regularity (SRI) and surface asymmetry (SAI) were used to monitor the results of PRK with or without AK. RESULTS: At 6 months, 95.6% eyes had an uncorrected visual acuity of 20/40 or better, 90% eyes were within +/-1.0 diopter of emmetropia, and 3.1% eyes lost two lines of best-corrected vision. No eyes lost more than two lines of best-corrected vision. Mean refractive astigmatism was reduced, but mean SAI and SRI were increased, 6 months after PRK. Uncorrected vision, best-corrected vision, and predictability decreased, whereas SAI and SRI increased, with increasing attempted correction. CONCLUSION: PRK, with or without AK, effectively reduced myopia in all eyes by 6 months after surgery. Predictability tended to decrease with increasing attempted correction, even for eyes with relatively low to moderate myopia. PRK may induce surface asymmetry and irregularity at 6 months, and these alterations tend to be greater as the attempted correction increases.

Astigmatism↗

Effect of coacervated alpha-elastin on proliferation of vascular smooth muscle and endothelial cells.

The arterial wall injury associated with arterial graft implantation causes smooth muscle cells (SMCs) in the media to migrate and proliferate in the intima at the graft-artery junction resulting in anastomotic intimal hyperplasia (AIH). An important step in developing a small-diameter prosthesis may be to stimulate endothelialization and thereby inhibit AIH. In this study, we investigated the effect of coacervated and crosslinked alpha-elastin on proliferation of SMCs and endothelial cells (ECs) in vitro. Coacervation is an important step in the conversion of proelastin to make an elastin fiber in vivo. SMCs and ECs were prepared from porcine aortic media and endothelium, respectively. SMCs and ECs (three to five passages, 4 x 10[4] cells/well) were seeded onto 12 well plates, coated and crosslinked with 0 or 10 mg/mL of coacervated alpha-elastin. After the 1st, 2nd, or 3rd day of cultivation, proliferation was assayed by scintillation counting of [3H]-thymidine incorporation. For the 4th day only, 0, 0.1, 1, 10 mg/mL concentration of coacervated alpha-elastin was coated and crosslinked. SMC proliferation (1st, 2nd day: p<0.005; 3rd, 4th day: p<0.0001) was significantly inhibited over time and dose dependently, eg, 0.1 mg/mL (45.7+/-2.3%: % of control p<0.005), 1 mg/mL (5.9+/-0.7%, p<0.0005), 10 mg/mL (2.8+/-0.4%, p<0.0005). EC proliferation was inhibited over time by 10 mg/mL of coacervated alpha-elastin (2nd, 3rd day: p<0.005; 4th day: p<0.0001), but proliferation (132.8+/-9.9%: % of control p=NS) was stimulated by 0.1 mg/mL of coacervated alpha-elastin. These results suggest that coating and crosslinking a coacervated alpha-elastin into the structure of arterial prosthesis may inhibit AIH and stimulate endothelialization.

Alkanesulfonic Acids↗

Keratocyte apoptosis after corneal surgery.

PURPOSE: Programmed cell death (apoptosis) is the controlled death of cells that occurs with minimal collateral damage to surrounding cells or tissue during development, homeostasis, and wound healing. The authors hypothesize the keratocyte apoptosis is an initiating factor in the wound-healing response after refractive surgical procedures. To evaluate the effects of different corneal manipulations, keratocyte apoptosis was examined qualitatively and quantitatively after traditional epithelial scrape-photorefractive keratectomy (PRK), transepithelial PRK, removal of a cap of superficial cornea using a microkeratome, production of a flap of superficial cornea with a microkeratome, and laser-assisted in situ keratomileusis (LASIK) compared with unwounded controls in rabbit corneas. METHODS: Refractive surgical procedures or their components were performed in rabbit eyes. Keratocyte apoptosis was monitored using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling assay to detect DNA fragmentation. Cellular morphologic changes were evaluated by electron microscope examination. RESULTS: Keratocyte apoptosis was noted with each refractive procedure or corneal manipulation and was variable from eye to eye with each procedure. Transepithelial PRK was associated with the lowest levels of central corneal apoptosis, even if the stromal surface was scraped after the procedure. Keratocyte apoptosis is confined to the superficial stroma extending to a depth of approximately 50 microns to 75 microns after epithelial scrape-PRK and transepithelial PRK. Apoptosis was noted in the deeper central corneal keratocytes located anteriorly and posteriorly to the lamellar cut in LASIK. CONCLUSIONS: There are qualitative and quantitative differences in keratocyte apoptosis between LASIK, epithelial scrape-PRK, and transepithelial PRK. Epithelial injury is an important factor modulating keratocyte apoptosis. The level and distribution of keratocyte apoptosis, along with subsequent repopulation by activated stromal keratocytes, are likely to be important determinants of corneal wound healing associated with variability and regression after PRK and LASIK. Transepithelial PRK induces low levels of keratocyte apoptosis, and, therefore, this approach may be useful for treating higher levels of myopia and for retreatment after regression.

Animals↗

Analysis of telomere lengths in human corneal endothelial cells from donors of different ages.

PURPOSE: To investigate the telomere hypothesis of cellular aging as the mechanism for cell cycle arrest in normal human corneal endothelium. METHODS: The corneal endothelium and epithelium from 21 human corneas from 13 donors 5 weeks to 84 years of age were dissected and frozen at -70 degrees C. Purified DNA, digested with the restriction enzyme, HinfI, was run on 0.7% agarose gels, probed with radiolabeled (AATCCC)4, and exposed to a phosphor screen. The length of the terminal restriction fragment (TRF) was determined by densitometry. RESULTS: The cells of the corneal endothelium had TRF lengths ranging from 11.0 to 14.0 kbp (mean, 12.2 +/- 0.9). Corneal epithelial specimens showed TRF lengths that were always less than (mean, 10.4 +/- 1.0; range 9.0-12.0) the corresponding endothelial TRF lengths. Human corneal endothelial cells, transformed with human papillomavirus type 16 oncogenes E6 and E7, showed decreasing TRF lengths from 11 kbp at population doubling level (PDL) 15 to 9.5 kbp at PDL 73. Neither the endothelial and epithelial cells from human donors nor the transformed pre-immortalized human endothelial cells showed evidence of telomerase activity. CONCLUSIONS: Human corneal endothelial cells have long telomeres throughout life. Their limited replicative ability does not appear to result from critically short telomere lengths.

Adolescent↗

Impact an anatomical site on bacteriological and clinical outcome in the management of intra-abdominal infections.

The clinical and bacteriological results of treatment for 429 patients who had intra-abdominal infection were analyzed to determine whether the anatomical origin of peritonitis influenced outcome. All patients had received effective broad spectrum antimicrobial therapy and operation in four multicenter trials. The diagnoses of infection were categorized into three sites: upper gastrointestinal tract, complicated appendicitis, and lower gastrointestinal tract. Clinical response rates were excellent for complicated appendicitis and were lowest for infections related to the upper gastrointestinal tract. Bacteriological response rates were also lower for upper gastrointestinal tract organisms and were highest for isolates associated with complicated appendicitis. There were no deaths in the 213 patients who had infection associated with appendicitis. Seven deaths occurred in the 86 patients (81%) with an upper gastrointestinal site of infection, and nine deaths occurred in the 130 patients (6.5%) with lower gastrointestinal site of infection. Mortality was related to recurrent intra-abdominal infection after an unsuccessful primary operation and a serum albumin less than 25 g/l. Clinical trails of antimicrobials for intra-abdominal infection should consider stratification of patients according to these three levels of alimentary tract perforation when the site is known preoperatively. Patients who have infection secondary to previous surgery or who are malnourished represent a higher risk group even with appropriate antibiotics.

Adult↗

Signaling by HGF and KGF in corneal epithelial cells: Ras/MAP kinase and Jak-STAT pathways.

PURPOSE: To characterize the signaling pathways used by hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in human corneal epithelial cells. METHODS: Cultures of SV40 large T antigen-transfected human corneal epithelial cells were treated with recombinant human HGF or KGF at 50 ng/ml to 100 ng/ml for 5 to 30 minutes and harvested for protein isolation. Immunoprecipitation was performed with antisera to signal transducers and activators of transcription 1 (STAT1), STAT3, Janus kinase 1 (Jak1), Shc, Grb2, Sos1, and HGF receptor (met). Immunoprecipitated proteins were analyzed by western blot analysis. Gel retardation experiments were carried out with first-passage human corneal epithelial cells to detect binding of STATs to the high affinity c-sis (platelet-derived growth factor) inducible DNA element (hSIE). Effects of HGF, KGF, and kinase inhibitors on mitogen-activated protein kinase (MAPK) activation were evaluated by western blot analysis and enzymatic assays. RESULTS: In human corneal epithelial cells, the phosphorylation of adapter protein Shc (52- and 66-kDa isoforms) was enhanced by HGF, but not by KGF. Phosphorylated HGF receptor coimmunoprecipitated with Shc, Grb2, and Sos1. Hepatocyte growth factor or KGF rapidly activated MAPK in corneal epithelial cells. The activation of MAPK (p42 and p44) by HGF or KGF was transient and decreased gradually within 1 hour. MAPK kinase 1 (MEK1) inhibitor PD098059 or the protein tyrosine kinase inhibitor genistein blocked MAPK activation. Activation of MAPK induced by HGF was partially inhibited by protein kinase C inhibitor calphostin C. Hepatocyte growth factor and KGF had no effect on the activation of Jak-STAT cascade components that are activated by epidermal growth factor. CONCLUSIONS: Hepatocyte growth factor and KGF activate Ras-MAPK pathways in human corneal epithelial cells. There may be at least two routes used by HGF in transmitting signals from its receptor to the MAPK cascade. One is the receptor-Grb2/Sos complex to the Ras pathway, and the other is through protein kinase C. Hepatocyte growth factor and KGF did not activate the Jak-STAT cascade components STAT1, STAT3, or Jak1 in corneal epithelial cells.

Blotting, Western↗

Everett Kinsey Lecture. Keratocyte apoptosis in refractive surgery.

PURPOSE: The purpose of this paper is to review the relevance of keratocyte programmed cell death (apoptosis) in response to epithelial injury to corneal wound healing following refractive surgery and the pathogenesis of corneal diseases such as keratoconus. METHODS: The TUNEL assay (to detect DNA fragmentation in situ) DNA laddering assay, and transmission electron microscopy have been used to detect apoptosis in human and animal corneas and cultured corneal cells. Molecular and cell biologic techniques have been used to study the cytokine-receptor systems that are involved in modulating apoptosis in the cornea. RESULTS: Keratocyte apoptosis, mediated through the release of cytokines such as soluble Fas ligand and interleukin-1 from the injured epithelium, occurs following refractive surgical procedures like photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Keratocytes that die in the anterior stroma following PRK or along the lamellar cut following LASIK are replenished in 2 to 4 days by proliferation and migration. The replenishing cells are activated myofibroblastic keratocytes that produce collagen, hyaluronic acid, growth factors modulating epithelial healing, and other components of the wound healing response. Keratocyte apoptosis can be inhibited by transepithelial PRK (probably by photodisruption of the apoptotic cytokines in the epithelium) or pharmacologic agents. CONCLUSIONS: Keratocyte apoptosis may be an initiator of the wound healing response in the cornea. Control of this response has the potential to regulate wound healing in the cornea in response to PRK or LASIK. Recent evidence suggests that keratocyte apoptosis mediated by chronic epithelial injury could have a role in the pathogenesis of keratoconus.

Animals↗

Cultured human trabecular meshwork cells express functional growth factor receptors.

PURPOSE: To compare the mRNA expression of growth factor receptors in cultured human trabecular meshwork (HTM) cells with ex vivo HTM tissues and to determine whether HTM cells generate a physiologic response after exposure to exogenous growth factors. METHODS: The reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the expression of various growth factor receptor mRNAs using early passaged, cultured HTM cells from donors of several ages. RT-PCR on ex vivo HTM tissues from healthy donors and donors with glaucoma were also used to compare and contrast mRNA expression with cell culture results. After the exogenous administration of growth factors, cell proliferation and extracellular acidification rate studies were used to measure the functional responses of HTM cells to growth factors. RESULTS: Amplification products of the expected size for 15 growth factor receptors were detected in cultured HTM cells and in ex vivo HTM tissues. The administration of exogenous growth factors showed that (a) hepatocyte growth factor (HGF), epidermal growth factor (EGF), insulinlike growth factor (IGF)-1, tumor necrosis factor (TNF) alpha, platelet-derived growth factor (PDGF)-AA, PDGF-BB, PDGF-AB, and basic fibroblast growth factor (FGF-2) stimulated cell proliferation, whereas FGF-1 (acidic), transforming growth factor (TGF) alpha, interleukin (IL)-1alpha, nerve growth factor (NGF), and FGF-7 (keratinocyte growth factor [KGF]) had no significant influence on cell proliferation; (b) TGF-beta isoforms significantly inhibited EGF-stimulated trabecular meshwork cell proliferation; and (c) FGF-1 (acidic), TGF-alpha, EGF, IL-1alpha, IL-1beta, HGF, TNF-alpha, PDGF-AA, and IGF-1 significantly stimulated extracellular acidification, whereas FGF-2 (basic), FGF-7 (KGF), TGF-beta1-beta3 and NGF had no significant influence on extracellular acidification. CONCLUSIONS: These studies show that mRNA for numerous growth factor receptors can be detected in cultured HTM cells and in ex vivo HTM tissues. They also show that many of the receptors are functional, because exogenous growth factor administration elicits a physiologic response. In vivo, these receptors may be activated by growth factors present within the aqueous humor (aquecrine/paracrine) or by growth factors synthesized and released locally by trabecular meshwork cells themselves (autocrine). Specific growth factors acting through high-affinity receptors may be involved in maintaining the normal microenvironment of the HTM and also may be involved in the pathogenesis of primary open-angle glaucoma.

Adolescent↗