Vascular endothelial cadherin expression in human carotid atherosclerotic plaque and its relationship with plaque morphology and clinical data.

OBJECTIVES: To determine the relationship between Vascular Endothelial (VE)-cadherin expression in carotid plaques, carotid plaque morphology and clinical findings of carotid disease. MATERIALS AND METHODS: Fifty-three formalin-fixed, paraffin embedded specimens of human carotid atherosclerotic plaque obtained by endarterectomy and 20 normal postmortem arteries (control group) were studied. Thirty patients were symptomatic and 23 asymptomatic. The expression of VE-cadherin was examined by an avidin-biotin immunoperoxidase technique using specific monoclonal antibodies against this molecule. We used a scale for the estimation of the expression of the VE-cadherin, in which negative expression was indicated by 0, weak expression by 1, and strong expression by 2. In serial sections we also determined the cellular phenotype of atherosclerotic plaques: i.e. the endothelial cells (F8), macrophage (CD68) and smooth muscle cells. Possible relations between variables in statistical analysis were examined by the chi-square test or Fisher's exact test. RESULTS: Expression of VE-cadherin was observed in small newly established vessels, particularly in areas with intense inflammatory infiltrations by macrophages and leucocytes. A strong expression of VE-cadherin was evident particularly in symptomatic instead in asymptomatic patients (43% vs. 13%, p=0.057), in high degree stenosis group (81% vs. 0%, p=0.005), and in patients with ischaemic infarct in brain scan (71% vs. 23%, p=0.021). On the other hand, there was no relation between molecule expression and plaque ultrasonic characteristics (echogenic or echolucent, p=0.499). Finally, there was a significant statistical correlation in the expression of VE-cadherin and the histological type of the plaque, namely fibrotic and complicated plaques. Strong VE-cadherin expression was observed in 64% of complicated plaques instead of 6.5% in fibrotic plaques (p=0.001). CONCLUSION: An intense expression of VE-cadherin in carotid plaques is linked with plaque instability, high degree of stenosis and clinical events. This molecule seems to be a marker of progression of the atherosclerotic plaque.

Cell senescence and a mechanism of clonal evolution leading to continuous cell proliferation, loss of heterozygosity, and tumor heterogeneity: studies on two immortal colon cancer cell lines.

Extensive karyotypic analysis was performed on early and late passages of two continuous human cell lines, SW480 and SW620, that were derived from the same colon cancer patient. We cultivated these two cell lines in vitro for a period of 24 months and periodically examined their chromosome constitution. SW480 cells, from passage 138, were injected subcutaneously into 20 nude mice. The tumors that grew in nude mice were then cultivated in vitro for several passages to compare histopathologic findings and tumor growth patterns with clonal chromosomal profiles. Despite some karyotypic diversity, the two cell lines exhibited common marker chromosomes and followed similar patterns of evolution. During subsequent passages, acquisition of new chromosomal abnormalities gave rise to sidelines with a near-diploid genome that frequently underwent endoreduplication. Genomic instability seemed to play an important role in the emergence, growth, and subsequent elimination of the heterogenous sidelines by selection, clonal expansion, and cell death by senescence. Despite continuous growth, both the cell lines occasionally showed telomeric associations and random dicentric and multicentric formations. These lesions were considered evidence of cell senescence and were related to the disappearance of particular sidelines through evolution. Successful evolutionary steps were characterized by elimination of pre-existing marker chromosomes that were subsequently replaced in the karyotype by their cytologically intact homologous chromosomes possibly after selective endoreduplication. Frequent loss of heterozygosity for the chromosomes taking part in this process is postulated. We suggest that one of the mechanisms by which cancer cells bypass senescence may be related to their potential for continuous clonal diversification.

In vitro effects of heparin on SW480 tumor cell-matrix interaction.

We investigated the in vitro effects of heparin on the growth and interaction of SW480 colon adenocarcinoma cells with the extracellular matrix proteins laminin, fibronectin and collagen IV. Cell adhesion assays were performed in wells precoated with the proteins mentioned. Tumor cell migration and invasiveness were assayed in Transwell cell culture chambers. SW480 cell adhesion to the matrix proteins and migration to laminin/fibronectin precoated filters were inhibited by heparin in a dose- dependent manner, whereas cell growth and invasion through collagen IV gel were not affected. Our results suggest that heparin influences the SW480 cell-matrix interaction in vitro and inhibits crucial steps of the metastatic process in an experimental model.

Effect of vasa vasorum flow on structure and function of the aorta in experimental animals.

BACKGROUND: It is known that vasa vasorum flow contributes substantially to the nutrition of the outer layers of the thoracic aorta. This investigation was undertaken to test the hypothesis that impairment of vasa vasorum flow would alter the structure of the aortic wall and change the elastic properties of the aorta. METHODS AND RESULTS: The periaortic fat that contain the vasa vasorum for the ascending aorta was removed in seven anesthetized dogs, and the results were compared with those obtained from six weight-matched sham-operated control dogs. Aortic pressures, aortic diameters, and aortic distensibility were obtained before and 30 minutes and 15 days after removal of the periaortic vasa vasorum network. Aortic pressures were measured directly with a fluid-filled catheter. Aortic diameters were measured simultaneously with aortic pressures with an elastic, air-filled ring connected to a transducer. Aortic distensibility was calculated by the formula 2 x pulsatile change in aortic diameter/(diastolic aortic diameter x pulse pressure). Histology was performed in transverse blocks of aortic wall at the end of the experiment in both groups. The efficacy of the technique for the interruption of vasa vasorum blood supply to the aortic wall was demonstrated by histology in four additional animals that were killed without removal of vasa vasorum (two animals) and immediately after vasa vasorum removal (two animals). At baseline, heart rate, aortic pressures, aortic diameters, and aortic distensibility were similar in the two groups. A significant decrease in aortic distensibility was observed 30 minutes and 15 days after removal of the vasa vasorum in the experimental group (baseline, 3.453 +/- 1.023; 30 minutes, 2.521 +/- 0.760; 15 days, 1.586 +/- 0.488 10(-6).cm2.dyn-1; F = 9.532, P < .001). No changes were observed in aortic distensibility in the control group during the experiment. Histology of the aorta revealed medial necrosis, alterations of the elastin fibers, and a trend (P = .055) for altered collagen-to-elastin ratio in a region occupying more than the one (outer) half of the media of the experimental group animals. No changes were observed in the control group. CONCLUSIONS: The findings of the present study demonstrated that interruption of vasa vasorum flow led to an acute decrease in the distensibility of the ascending aorta. Moreover, structural changes of the aortic wall and further deterioration of the elastic properties of the aorta occurred 15 days after vasa vasorum removal.

The innervation of the human meniscus.

Fourteen menisci from seven anatomic specimens were examined to identify their innervation. After staining by a modified gold chloride method, the menisci were sectioned on a sliding microtome and were studied under a light microscope. Free nerve endings in the peripheral and the medial thirds of the meniscal body were identified, and three types of encapsulated mechanoreceptors were found in the anterior and posterior horns. Based on these findings and a review of the relevant literature, it is considered that menisci both receive and transmit proprioceptive information. Therefore, they not only are stabilizers of this joint, but also contribute to the function of deep sensitivity.

Mechanoreceptors in the posterior cruciate ligament. Histologic study on cadaver knees.

The purpose of the study was to identify mechano-receptors in the healthy, human posterior cruciate ligament. Ten ligaments from 10 fresh cadavers were studied with light microscopy. In addition to free nerve endings, two types of encapsulated mechanoreceptors were identified. They were located at the femoral and tibial attachments, and on the surface of the ligament. These findings support the hypothesis that the posterior cruciate ligament has an anatomic basis for a discriminating afferent flow of nerve impulses to the central nervous system. Therefore, its neural network may play a role in regulating the contraction of muscle groups that are fundamental to knee stability.

Jeune syndrome associated with pancreatic fibrosis.

Jeune syndrome, a rare autosomal recessive disorder characterized by skeletal abnormalities of the thorax and extremities, is associated with respiratory distress in infancy, hepatic fibrosis in some instances, and renal failure that may develop later. We report here one additional feature, pancreatic fibrosis. The association of pancreatic fibrosis with Jeune syndrome has been previously described, but it has not been appreciated as a stable and important manifestation of this disorder.

Arthrogryposis multiplex congenita, Pena-Shokeir phenotype, with gastroschisis and agenesis of the leg.

A young mother had a stillborn infant at 33 weeks' gestation, the pregnancy complicated by polyhydramnios. The parents were unrelated, healthy, and both had a normal karyotype. The infant had multiple malformations such as ankylosis, facial anomalies, and pulmonary hypoplasia. A severe gastroschisis and agenesis of the right leg were also present. The neuropathologic findings were those of marked atrophy of anterior horn motor cells in the spinal cord and neurogenic muscle atrophy. This is a case of Pena-Shokeir syndrome with two additional features: gastroschisis and agenesis of the right leg. This syndrome represents a lethal form of arthrogryposis multiplex congenita, and the essential neuropathologic findings are marked reduction in the number of spinal motor cells and neurogenic muscle atrophy.

Cyclopia and maternal ingestion of salicylates.

Salicylates are teratogens in animals, but their teratogenicity in man remains controverted. The possibility that massive oral intake in the first 3 months of pregnancy may induce malformations has not been eliminated. We report a second case of cyclopia associated with daily maternal ingestion of up to 4 g of acetylsalicylic acid in the first trimester.

Spindle cell carcinoma (pseudosarcoma) of the anus: a light, electron microscopic and immunocytochemical study of a case.

We report a case of polypoid spindle cell squamous carcinoma (pseudosarcoma) occurring in the anal canal. Electron microscopic findings and the demonstration of keratin by an immunoperoxidase method, gave clear cut evidence of the epithelial nature of the sarcomatoid cells forming this tumour. To our knowledge, this is the first reported case in the literature.