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Biomedical subjects

J J Lopez

Publications and source records attributed to J J Lopez.

30 records · Page 2Linked to original sources
PubMed1996

Enhanced microvascular relaxations to VEGF and bFGF in chronically ischemic porcine myocardium.

Changes in the vascular responses to vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in chronically ischemic myocardium have not been investigated. Ameroid constrictors were placed on the proximal left circumflex (LCX) artery of seven Yorkshire pigs. Seven to nine weeks later, myocardial blood flow in the collateral-dependent LCX region was reduced, compared with that in the normally perfused left anterior descending (LAD) region. Both growth factors elicited significant relaxations of coronary microvessels. Relaxations to both VEGF and bFGF were inhibited in the presence of either NG-nitro-L-arginine or genistein, suggesting that the relaxations are through the tyrosine kinase-mediated release of endothelium-derived nitric oxide. Microvascular relaxations to both VEGF or bFGF were significantly greater in vessels harvested from the collateral-perfused LCX region, compared with those taken from the normally perfused LAD region. However, relaxation to the endothelium-dependent vasodilator ADP, which does not operate through a tyrosine kinase receptor, was reduced in the collateral-perfused region, compared with the normally perfused territory, suggesting a possible link of tyrosine kinase to the enhanced relaxations to VEGF and bFGF in collateral-perfused coronary microvessels. Northern analysis showed increased expression for both VEGF receptors (flk-1, flt-1) as well as the bFGF receptor 1 (FGFR-1) in the collateral-perfused region compared with that in the normally perfused region. This suggests that the increased relaxation responses to VEGF and bFGF in the ischemic myocardium may be related to increased gene expression of the respective tyrosine kinase receptors.

Adenosine Diphosphate↗
PubMed1995

Beta-adrenergic modulation of the collateral-dependent coronary microcirculation.

The effect of chronic, collateral-dependent perfusion on beta-adrenergic coronary microvascular responses was examined. Ameroid constrictors were placed on the proximal left circumflex (LCx) coronary artery in 16 pigs. In 8 pigs, heparinized saline containing vascular endothelial growth factor (VEGF) was administered into the perivascular space of the proximal LCx artery using an implanted osmotic pump. After 5-7 weeks, coronary arterial microvessels (70-150 microns) were studied in a pressurized (40 mm Hg) no-flow state with video-microscopy. beta-Adrenoceptor-mediated relaxations of isolated microvessels from the collateral-dependent LCx region to isoproterenol (P < 0.01) were markedly reduced, as were those to the adenylate cyclase activator forskolin (P < 0.01), compared to the respective response of vessels from the normally perfused left anterior descending artery region. Responses to the Gs-protein activator NaF showed a similar trend, but the differences were not significant. Chronic treatment with VEGF normalized responses to isoproterenol, NaF, and forskolin in the collateral-dependent LCx region. Blood flow in the LCx region increased in both control (P < 0.01) and VEGF-treated (P < 0.05) groups during rapid atrial pacing. The absolute increase in LCx blood flow was greater in the VEGF group than in the control group at rest (P < 0.05), but not during rapid pacing. Thus, beta-adrenergic microvascular relaxation is impaired in the collateral-dependent coronary microcirculation. The periadventitial delivery of VEGF improves myocardial perfusion to the collateral-dependent area and preserves beta-adrenergic-mediated relaxation of microvessels in the collateral-dependent myocardium.

Animals↗
PubMed1995

Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis.

Coronary occlusive disease is the leading cause of death in industrial nations and affects one in four adults. Although heart attacks are caused by occlusion of a coronary artery, some patients have occlusions without infarction because they have sufficient collateral vessels providing an alternate pathway for blood supply. Vascular endothelial growth factor (VEGF) is an angiogenic peptide that can stimulate collateral vessel development in the ischaemic myocardium. We used magnetic resonance imaging (MRI) and image processing to identify and quantify non-invasively the benefits related to VEGF infusion on collateral development in the heart. This was accomplished as a placebo-controlled study in the porcine model of chronic ischaemia that most closely mimics the human pathophysiology of progressive coronary occlusion. Image series converted to a space-time map demonstrated that with treatment the ischaemic zone was smaller and the contrast arrival delay was less, which resulted in better ejection fraction and regional wall thickening. These findings demonstrate in a manner applicable to humans, that VEGF improves collateral blood supply, resulting in improved cardiac global and regional function after and in spite of coronary artery occlusion.

Angiogenesis Inducing Agents↗
PubMed1994

Distribution and function of cardiac angiotensin AT1- and AT2-receptor subtypes in hypertrophied rat hearts.

To determine distribution and function of cardiac angiotensin (ANG) II receptor AT1 and AT2 subtypes in left ventricular (LV) hypertrophy (LVH), ANG II (10(-8) M) was infused into isolated rat hearts with hypertrophy from aortic banding and into sham-operated controls. ANG II was infused alone or in the presence of AT1 inhibitor [losartan (10(-5) M) or CL-329167 (10(-7) M)] or AT2 inhibitor [CG-42112A (10(-8) M]. ANG II alone caused less increase in coronary vascular resistance (CVR) in LVH compared with control hearts (19 vs. 39%; P < 0.01), although baseline CVR was higher in LVH hearts. This was prevented by AT1 but not AT2 antagonists. ANG II also increased LV end-diastolic pressure in LVH hearts, signifying decreased diastolic relaxation that was prevented by AT1 but not AT2 inhibition. Characterization of ANG II binding sites in LV membrane preparations revealed similar dissociation constants between groups (1.6 +/- 0.95 vs. 2.2 +/- 2.0 nM; not significant) but lower maximum binding capacity in the LVH group (21.1 +/- 5.9 vs. 33.5 +/- 3.0 fmol/mg protein; P < 0.05). Competition assays demonstrated that control left ventricles contain predominantly the AT1 subtype (68.8 +/- 20%), whereas LVH ventricles contain primarily the putative AT2 subtype (59.8% +/- 10.8%; P < 0.05). This suggests that receptor subtype redistribution occurs in LVH with AT1 subtype down-regulation. Nonetheless, the AT1 subtype mediates the effects of ANG II on coronary tone and diastolic dysfunction in pressure-overload hypertrophy.

Angiotensin II↗
PubMed1994

Primary liposarcoma of the larynx. Case report and literature review.

Laryngeal liposarcoma is an unusual tumor. Only 16 cases have been previously reported. We describe a new case of well-differentiated laryngeal liposarcoma and review the literature. The tumor was treated by surgical removal. Immunohistochemical study showed an immunophenotype consistent with liposarcoma. The case described is of the oldest patient (83 years old), the second to be found in a woman, and the second to be localized to one true vocal cord (according to the literature reviewed). The patient is still free of tumor 2 years later. The treatment and prognosis of liposarcoma of the larynx are discussed.

Aged↗
PubMed1994

CHOP chemotherapy of intermediate and high-grade non-Hodgkin's lymphoma.

The results of CHOP treatment in 63 patients with intermediate and high-grade non-Hodgkin's lymphoma (Working Formulation D to I), Ann Arbor stage I to IV were analyzed. The response rate was 87%, 71% complete remission and 16% partial remission with a mean duration of 22 months. The 5-year actuarial survival was 61% (95% confidence interval, 51-70%). The treatment was well tolerated and no deaths due to acute toxicity were observed. Poor prognostic factors in univariate analysis were: high-grade histology, stages III and IV, B symptoms, > or = 4 affected lymph node regions, Karnofsky index < or = 70, erythrocyte sedimentation rate (ESR) > 60 mm, haemoglobin < 100 g/l and elevated lactic dehydrogenase (LDH). Poor prognostic factors in multivariate analysis were: high-grade histology, stages III and IV, haemoglobin < 100 g/l and elevated LDH. In summary, good results were obtained with CHOP chemotherapy, without severe toxicity.

Actuarial Analysis↗
PubMed1992

A prospective study of tumor markers CA 125 and CA 19.9 in patients with epithelial ovarian carcinomas.

In a prospective study, CA 125 and CA 19.9 serum levels were measured in 229 patients with ovarian cancer [121 with active disease, 108 in complete remission (CR)], and in 20 patients with other malignancies. Abnormal levels of CA 125 were found in 90% of patients with active ovarian cancer, in 1.8% of those in CR and in 38% of cases with other malignancies. Abnormal CA 19.9 serum levels were found in 36, 9 and 48% of these groups, respectively. Serum levels of both tumor markers were related to tumor stage and histological type. The highest levels of CA 125 were found in serous adenocarcinoma and the lowest in the mucinous type (p < 0.0001). In contrast, significantly higher CA 19.9 values were found in mucinous carcinoma than in other histologies (p < 0.0001). CA 125 and CA 19.9 were useful for monitoring disease activity in 88.3 and 32%, respectively, while one or other tumor marker was useful in 92% of patients. At the time of the second-look operation, abnormal CA 125 serum levels were found in 32% (6/19) of patients with active disease and in none of those with CR (0/38). CA 125 sensitivity was 83% (5/6) in those patients with residual tumor > 2 cm and in 8% (1/13) in those with tumor < 2 cm. CA 19.9 values were abnormally high in 16% of cases with persistent disease and in 11% of CR patients. In conclusion, our results confirm that CA 125 is a useful marker in ovarian carcinoma. CA 19.9 improves the results obtained with CA 125 alone only in mucinous adenocarcinomas.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

High-dose chemotherapy with bone marrow rescue for treatment of Hodgkin's disease.

Between December 1st 1984 and July 1st 1991, 20 patients, 11 males and 9 females, median age 36 years (range 14-54) with Hodgkin's disease were treated with high dose chemo-radiotherapy followed by autologous bone marrow rescue. At the time of autologous bone marrow transplantation, 8 patients were in complete remission, 9 in sensitive relapse and 3 were resistant to conventional treatments. There were 3 early procedure-related deaths: 1 cardiac failure due to cyclophosphamide treatment, 1 veno-occlusive disease, and 1 patient died from CMV interstitial pneumonitis, 4 months after ABMT. Of the 17 other patients, 15 are alive, 12 in complete remission, 2 in relapse and 1 patient is not evaluable due to short-follow-up follow-up. Disease free survival is 65% at 20 months with a follow-up of 60 months. There is a trend for a better disease-free survival in patients in complete remission at the time of autologous bone marrow transplantation vs patients in sensitive relapse, although it does not reach statistical significance (80% vs 37%).

Adolescent↗
PubMed1988

Hamartomatous solitary polyp with malignant progression in the jejunum. A histochemical and immunohistochemical study by light and electron microscopy.

A case of solitary hamartomatous jejunal polyp with adenomatous and carcinomatous changes in a 16-year-old girl is reported. In the hamartomatous polyp, neutral and acid non-sulfate mucosubstance was detected, principally in goblet cells; carcinoembryonic antigen was demonstrated on the surfaces of the microvilli and luminal border of the crypts and glands; absorptive columnar, goblet, argentaffin, argyrophil and Paneth cells were evident. The adenomatous and, mainly, the carcinomatous areas revealed a decreased amount of mucosubstance and a variable degree of positive intracytoplasmic staining for carcinoembryonic antigen. With electron microscopy, the adenomatous areas showed columnar absorptive cells and mucus-secreting goblet cells; also immature columnar cells were observed in the dysplastic zones. To our knowledge, this is the first study to document the histochemical, immunohistochemical and ultrastructural features of a hamartomatous polyp with neoplastic transformation.

Adolescent↗
PubMed1987

Long-term survival in small cell carcinoma of the lung.

We analyzed the long-term survivors in a group of 255 patients with newly diagnosed small cell carcinoma of the lung (SCCL) between January 1978 and July 1983. Long-term survivors were defined as those patients free of cancer 2 years after initiation of therapy. Only 6 patients (2.5%) were free of disease at this time. Two patients relapsed at 29 and 40 months from the start of chemotherapy. Both patients were retreated with chemotherapy, and one of them achieved a complete response. Despite the increase in median survival in SCCL with chemotherapy over the past 10 years, long-term prognosis remains very poor employing standard treatments.

Aged↗