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Biomedical subjects

J Quigley

Publications and source records attributed to J Quigley.

16 recordsLinked to original sources
PubMed1998

Podokinesis in endothelial cell migration: role of nitric oxide.

Previously, we demonstrated the role of nitric oxide (NO) in transforming epithelial cells from a stationary to locomoting phenotype [E. Noiri, T. Peresleni, N. Srivastava, P. Weber, W.F. Bahou, N. Peunova, and M. S. Goligorsky. Am. J. Physiol. 270 (Cell Physiol. 39): C794-C802, 1996] and its permissive function in endothelin-1-stimulated endothelial cell migration (E. Noiri, Y. Hu, W. F. Bahou; C. Keese, I. Giaever, and M. S. Goligorsky, J. Biol: Chem. 272: 1747-1753, 1997). In the present study, the role of functional NO synthase in executing the vascular endothelial growth factor (VEGF)-guided program of endothelial cell migration and angiogenesis was studied in two independent experimental settings. First, VEGF, shown to stimulate NO release from simian virus 40-immortalized microvascular endothelial cells, induced endothelial cell transwell migration, whereas NG-nitro-L-arginine methyl ester (L-NAME) or antisense oligonucleotides to endothelial NO synthase suppressed this effect of VEGF. Second, in a series of experiments on endothelial cell wound healing, the rate of VEGF-stimulated cell migration was significantly blunted by the inhibition of NO synthesis. To gain insight into the possible mode of NO action, we next addressed the possibility that NO modulates cell matrix adhesion by performing impedance analysis of endothelial cell monolayers subjected to NO. The data showed the presence of spontaneous fluctuations of the resistance in ostensibly stationary endothelial cells. Spontaneous oscillations were induced by NO, which also inhibited cell matrix adhesion. This process we propose to term "podokinesis" to emphasize a scalar from of micromotion that, in the presence of guidance cues, e.g., VEGF, is transformed to a vectorial movement. In conclusion, execution of the program for directional endothelial cell migration requires two coexisting messages: NO-induced podokinesis (scalar motion) and guidance cues, e.g., VEGF, which imparts a vectorial component to the movement. Such a requirement for the dual signaling may explain a mismatch in the demand and supply with newly formed vessels in different pathological states accompanied by the inhibition of NO synthase.

Animals↗
PubMed1996

Hostility predicts restenosis after percutaneous transluminal coronary angioplasty.

OBJECTIVE: To investigate the "toxic" total (potential for) hostility component of the type A behavior pattern (assessed by means of the structured interview) as it relates to prediction of restenosis after percutaneous transluminal coronary angioplasty (PTCA). DESIGN: Patients with single vessel or multivessel coronary artery disease in whom PTCA had been scheduled or done were administered the structured interview by one trained interviewer prospectively or retrospectively (blinded to angiographic endpoints). MATERIAL AND METHODS: A total of 41 patients underwent 53 initial balloon dilations on native arteries by 1 of 5 participating cardiologists. Inclusion criteria for this study were a successful initial PTCA and post-PTCA recatheterization if a patient complained of ischemic symptoms possibly related to restenosis. RESULTS: Of the 41 patients, 15 (36.6%) had restenoses at a total of 18 previous angioplasty sites. Patients with high total (potential for) hostility ratings were almost 2.5 times more likely to have restenosis than those with low total (potential for) hostility scores (95% confidence interval = 1.03 to 5.32). Logistic regression revealed that total (potential for) hostility scores predicted post-PTCA restenosis overall as well as when adjusted for gender and race. Total (potential for) hostility scores were also positively associated with the number of arteries restenosed (P = 0.01). CONCLUSION: This is the first report of type A total (potential for) hostility behavior conferring an increased risk for restenosis after PTCA. Its modification may be effective in reducing recurrent cardiac events. A coronary-prone behavior modification program for patients with persistent, same-site restenosis after PTCA has been initiated.

Aged↗
PubMed1996

Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo.

BACKGROUND: An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. OBJECTIVE: Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. METHODS: Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. RESULTS: VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25 patients with normal skin. CONCLUSION: VC-PMG is effective in reducing skin hyperpigmentation in some patients.

Ascorbic Acid↗
PubMed1991

BMY 30047: a novel topically active retinoid with low local and systemic toxicity.

In the treatment of various dermatological disorders, topically applied retinoids have potential therapeutic use with the advantage of improved localized activity and lower toxicity over systemically administered retinoids. However, most retinoids cause a significant degree of local irritation. In the present study, the ability to produce local activity with low local irritation potential was evaluated with a novel retinoic acid derivative. BMY 30047 (11-cis, 13-cis-12-hydroxymethylretinoic acid delta-lactone) is one of a series of retinoic acid derivatives in which the carboxyl function of the polar end was modified with the aim of achieving reduced local irritation and systemic toxicity while retaining the local therapeutic effect. BMY 30047 was evaluated and compared with all-trans retinoic acid for topical retinoid activity in several preclinical assay systems, including the utricle reduction assay in rhino mice, 12-o-tetradecanoylphorbol 13-acetate ester-stimulated ornithine decarboxylase induction in hairless mice and the UV light-induced photodamaged skin model in hairless mice. BMY 30047 was assessed for retinoid-type side effects by evaluating the skin irritation potential in rabbits after repeated topical application, and hypervitaminosis A-inducing potential in mice after i.p. injection. BMY 30047 demonstrated significant topical retinoid activity in several in vivo models with less skin irritation potential relative to the most used clinical concentrations of all-trans retinoic acid. BMY 30047 also showed very little systemic activity and did not produce any evidence of hypervitaminosis A syndrome at systemic doses 20 times greater than the no-effect dose of all-trans retinoic acid.

Administration, Topical↗
PubMed1978

An experimental model of acute immune-complex uveitis.

We developed an experimental model of anterior uveitis by injecting ovalbumin or bovine serum albumin into the anterior chamber of sensitized rabbits. All the eyes showed leakage of serum proteins into the aqueous humor within 30 min. and developed uveitis within 24 hrs. which lasted at least a week. On histological examination, large numbers of polymorphonuclear (PMN) leucocytes and only occasional mononuclear cells were seen in the iris, the ciliary body and the irido-corneal angle. Immunohistological examination revealed 7s gamma globulin in the walls of blood vessels, in the interstitium and inside the PMN leucocytes. Contact radiographs of eyes challenged repeatedly showed extensive neovascularization of the iris and ciliary body.

Animals↗
PubMedDate not supplied

Sarcomas of the female genital tract and pelvic soft tissues. A cluster of 14 cases in one year.

We report ten uterine and four extrauterine sarcomas encountered in a twelve month period (1989-90). The seven new cases of uterine sarcomas represent an estimated one third of all cases of malignancy of the corpus uteri, which were diagnosed at the gynaecology departments of St James's and Adelaide hospitals in one year. Overall, the prognosis was poor in the uterine sarcoma group-only one patient in clinically tumour free and five have succumbed to their disease. Delay in diagnosis especially in younger women with fibroid uterus contributed to this outcome.

Adenocarcinoma↗