Quantitative analysis of vessels with smooth muscle layer in astrocytic tumors: correlation with histological grade and prognostic significance

Angiogenesis plays an important role in the progression of astrocytic tumors and its evaluation is a major prognostic factor. Although the form of proliferating vessels ranges from fine capillaries to welldeveloped vascular structures with a smooth muscle layer, the characteristics of vascular smooth muscle cells (SMCs) are not understood in detail. We therefore examined the density, size and shape of tumor vessels, as well as CD34-immunoreactive (CD34-Vs) or α-smooth muscle actin-immunoreactive (SMA-Vs) vessels in 46 primary astrocytomas (grade II diffuse astrocytomas, n=11, grade III anaplastic astrocytomas, n=15, grade IV glioblastomas, n=20) and in normal brain tissues from 10 autopsies. We also examined the expression of high molecular weight caldesmon (h-CD, a marker of the contractile phenotype of smooth muscle) and of plateletderived growth factor receptor ß (PDGFR-ß). The SMAVs were significantly more dense and larger in grade IV than grade III, whereas those of CD34-Vs did not differ between grade III and IV. Changes in the shape of CD34-Vs and SMA-Vs correlated with histological grading. The expression of h-CD was reduced, whereas that of PFGFR-ß was increased in high gradeastrocytomas. Kaplan-Meier analysis indicated that the density of SMA-Vs, the size of both CD34 and SMA-Vs and PDGFR-ß expression were significant prognostic factors. These findings suggest that SMA-Vs are significantly associated with the progression of astrocytomas and that these vessels provide useful information for the histological diagnosis and survival of patients with these types of brain tumors

Critical role of von Willebrand factor and platelet interaction in venous thromboembolism

It has been generally considered that platelets are less important in venous thrombus formation. However, clinical studies have shown an association between venous thromboembolism (VTE) and von Willebrand factor (VWF). We therefore investigated the contribution of VWF and platelet interaction to the onset of VTE using tissues from autopsies and from an animal model. An immunohistochemical study revealed that glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A (erythrocyte-specific protein) and VWF were consistently localized in ilio-femoral venous thrombi and in pulmonary thromboemboli from 8 autopsied cases who died of VTE, and VWF was closely associated with GPIIb/IIIa and fibrin. Venous thrombi and pulmonary emboli contained significant amounts of GPIIb/IIIa and VWF, in addition to glycophorin A and fibrin, and the factors did not significantly differ between them. A rabbit model of VTE was developed by inserting a polyethylene tube into the iliac vein. The constituents of the induced thrombi were quite similar to those of human VTE. An antibody against VWF (AJW200), which inhibits interactions between the VWF A1 domain and platelet GPIb, significantly reduced venous thrombus formation and pulmonary thromboembolism in the model. These results suggest that VWF A1-platelet GPIb interaction plays a significant role in venous thrombus formation

Associations of intrauterine growth restriction with placental pathological factors, maternal factors and fetal factors; clinicopathological findings of 257 Japanese cases

Intrauterine growth restriction (IUGR) is the leading cause of fetal mortality and morbidity. As an etiology, each of placental findings, maternal factors and fetal factors has been reported to be associated with IUGR, although a comprehensive approach to examine all of these parameters as a cause of IUGR has not been reported. In the present study, therefore, we comprehensively examined the placental findings and maternal and fetal factors in the cases of IUGR (n=257, mean maternal age, 30 years; gestational weeks, 34 weeks) and normal growth pregnancies (n=258, mean maternal age, 30 years; gestational weeks, 33 weeks), and determined risk factors for IUGR. The prevalence of pregnancy hypertension (PHT) (19% vs. 8%, P<0.01), smoking habit (3% vs. 0.7%, P<0.05) and fetal anomaly (3.5% vs. 0.8%, P<0.05) were higher in IUGR cases than normal growth pregnancies. Pathologically, the prevalence of infarction (33% vs. 14%, P<0.05), fetal vessel thrombosis (22% vs. 6%, P<0.001) and chronic villitis (11% vs. 3%, P<0.001) were higher in IUGR cases than those in normal growth pregnancies. A multivariable regression analysis revealed that maternal factors (PHT), fetal factors (anomaly), and placental findings (infarction, fetal vessel thrombosis, and chronic villitis) are independently associated with increased risk of IUGR (all P<0.01)