Clinicopathological features of cutaneous lesions of adult T-cell leukaemia/ lymphoma.

BACKGROUND: Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). ATLL frequently involves the skin. OBJECTIVES: To correlate the clinicopathological features and prognosis in patients with ATLL and cutaneous lesions. METHODS: We examined the HTLV-I proviral state and the clinicopathological features of the cutaneous lesions in 80 patients with serum anti-ATL antibody, to clarify the correlation between macroscopic/histopathological findings and prognosis. Southern blot analysis was performed in all cases to detect monoclonal HTLV-I proviral DNA integration. RESULTS: The cutaneous lesions of 46 patients were positive for proviral DNA integration. The median survival time of patients with monoclonal proviral DNA integration in cutaneous lesions was 14 months, which was markedly shorter than that of patients negative for proviral DNA integration (72 months). Of the 46 patients with proviral DNA, 21 had solitary or multiple red nodules (including three with subcutaneous induration), eight had multiple red papules and 17 had erythema. Patients with papules and nodules had poorer prognosis than those with erythema. Histopathologically, the prognosis was poorer in patients with nodular or diffuse infiltration of medium-sized to large lymphoma cells, compared with those with perivascular infiltration of small to medium-sized lymphoma cells. CONCLUSIONS: Our results show a close correlation between clinicopathological features of HTLV-I-associated cutaneous lesions and prognosis.

Increased plasminogen activator inhibitor activity and diabetes predict subsequent coronary events in patients with angina pectoris.

BACKGROUND: Plasminogen activator inhibitor (PAI) is a marker of recurrence of myocardial infarction. Diabetes mellitus is also an important risk factor of coronary artery disease, including myocardial infarction and angina pectoris. AIM: We examined baseline plasma PAI activity levels, clinical variables, and angiographic findings and assessed them as prospective values for subsequent coronary events, such as sudden death, nonfatal myocardial infarction and coronary revascularization by percutaneous transluminal coronary angioplasty or coronary artery bypass surgery during the follow-up period. METHODS: We conducted a prospective study for 4 years of 249 consecutive patients admitted with angina pectoris. Blood samples for PAI were drawn at discharge. RESULTS: In the multivariate Cox proportional hazard model, PAI activity and diabetes mellitus were significant and independent risk factors (the risk increased by 10% in those with a higher PAI concentration and by 70% in diabetic patients). Event-free survival was reduced by higher PAI activity (> or = 8.4 IU/mL) and the presence of diabetes. The patients with higher PAI activity and diabetes had a 4.2-fold risk in comparison with the patients with lower PAI activity and no diabetes. However, patients with lower PAI activity were less likely to have coronary events even when they had diabetes. CONCLUSIONS: Higher PAI activity and diabetes predict subsequent coronary events in patients with angina pectoris. Diabetes has less prognostic value for subsequent coronary events in patients with lower PAI activity.

Difference in fibrinolytic activity between multivessel coronary spasm and one-vessel coronary spasm.

Plasminogen activator inhibitor activity was higher in 18 patients with multivessel spasm than in 20 patients with 1-vessel spasm and in 22 control patients. Tissue plasminogen activator antigen was also higher in patients with multivessel spasm than in those with 1-vessel spasm and control patients. The increased plasminogen activator inhibitor activity in patients with multivessel spasm indicates that the fibrinolytic system is more impaired in such patients than in those with 1-vessel coronary spasm; this may be related to the higher incidence of refractory angina during hospitalization and cardiac events during the follow-up period.

Increased plasma level of soluble E-selectin in acute myocardial infarction.

BACKGROUND: E-selectin, also known as endothelial cell leukocyte adhesion molecule-1, is a member of the selectin family of adhesion molecules and is expressed on vascular endothelial cells in inflammatory reactions. The induction of surface E-selectin expression by endothelial cells is considered a marker of activation. METHODS AND RESULTS: We examined the plasma soluble E-selectin (sE-selectin) level in 41 patients within 6 hours after the onset of acute myocardial infarction (AMI) and in 37 patients with stable exertional angina and 27 control patients. Blood samples were obtained on admission, after reperfusion therapy, and at 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 3 days, 5 days, 1 week, and 2 weeks after admission in the AMI group. In this group, 21 patients had a history of prodromal unstable angina before infarction and 20 had sudden onset of infarction. The plasma sE-selectin level (ng/mL) on admission was higher in the AMI group than in the stable exertional angina group and control group (38.5 +/- 3.1 vs 28.5 +/- 1.5, P <.01, 26.0 +/- 1.8, P <.01, respectively). In addition, plasma sE-selectin levels were higher in the patients with AMI with prodromal unstable angina than in those with a sudden onset of infarction on admission (44.7 +/- 5.4 vs 32.0 +/- 2.1, P <.05). The plasma sE-selectin level decreased slowly during the chronic phase both in patients with AMI with prodromal unstable angina (from 44.7 +/- 5.4 to 33.8 +/- 3.4, P <.01) and those with a sudden onset of infarction (from 32.0 +/- 2.1 to 24.9 +/- 2.4, P <.01). CONCLUSIONS: These results suggest that an increase of sE-selectin may reflect enhanced endothelial cell activation in patients with AMI. The higher sE-selectin level in patients with AMI with prodromal unstable angina may have been associated with repeated episodes of myocardial ischemia and reperfusion.

Increased blood vascular endothelial growth factor levels in patients with acute myocardial infarction.

Vascular endothelial growth factor (VEGF) is a growth factor for vascular endothelial cells in vitro. The present study was designed to determine whether serum VEGF levels increase in patients with acute myocardial infarction (AMI) compared with patients with stable exertional angina and control subjects, and to examine the serial changes of serum VEGF levels in patients with AMI. We examined serum VEGF levels by using antibody prepared from serum immunized with human VEGF(121). The serum VEGF level (pg/ml) was higher (p < 0. 0001) on admission in the patients with AMI (177 +/- 19) than in those with stable exertional angina (61 +/- 7) and control subjects (62 +/- 6). The serum VEGF level (pg/ml) of the patients with AMI was 177 +/- 19 on admission, 125 +/- 9 on day 3, 137 +/- 11 on day 5, 242 +/- 18 at 1 week, and 258 +/- 22 at 2 weeks after admission. The value was higher on admission than on day 3 after admission (p = 0.014), the values were higher at 1 week and 2 weeks than on admission, on day 3, and 5 (p < 0.01). Furthermore, there were correlations between peak VEGF levels at 1 week or 2 weeks after admission and peak creatine kinase levels. The increase of VEGF on admission in the patients with AMI may be due to the hypoxia of acute myocardial ischemia. The elevation at 1 week and 2 weeks from the onset may cause the development of collateral circulation in relation to the healing of the infarction site.

Co-localization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis.

Tissue factor (TF) initiates the extrinsic pathway of blood coagulation by acting as a cofactor for Factor VII. Inhibition of the Factor VIIa-TF complex is mediated by the tissue factor pathway inhibitor (TFPI), which is a serine protease inhibitor with three Kunitz-type domains. The localization of TF and TFPI protein has been examined immunohistochemically in various atherosclerotic lesions of coronary arteries from 22 autopsy cases and their messenger RNA expression has been confirmed by reverse transcription-polymerase chain reaction. Four types of atherosclerotic lesion (types I, II, III, and IV) were classified according to the method described by Stary et al. TF and TFPI were localized in endothelial cells, macrophages, macrophage-derived foam cells, and smooth muscle cells in the intimal lesions, medial smooth muscle cells, and endothelial cells of the microvessels in the adventitia. Immunohistochemical double staining revealed the co-localization of TF and TFPI in the endothelial cells and macrophages in four types of atherosclerotic lesions. In type III and IV lesions, the number of TF- and TFPI-positive cells was increased, accompanied by extracellular localization of TF and TFPI in the lipid core of atherosclerotic plaques. Fibrin deposition was found around TF- and TFPI-positive macrophages and in the lipid core of atherosclerotic plaques. TF and TFPI messenger RNA were detected more frequently in coronary arteries with type III and IV lesions than in those with type I and II lesions. The co-localization of TF and TFPI was demonstrated in various atherosclerotic lesions of coronary arteries and was shown to be intimately related to fibrin deposition in advanced atherosclerotic plaques. The co-localization of TF and TFPI may thus be closely associated with thrombogenicity in atherosclerotic lesions of coronary arteries.

Plasma soluble intercellular adhesion molecule-1 levels in coronary circulation in patients with unstable angina.

It has been suggested that active inflammation plays an important role in the pathogenesis of acute coronary syndromes, including unstable angina. Intracellular adhesion molecule-1 (ICAM-1) is a major ligand on the endothelial cells for adherence of the activated polymorphonuclear leukocytes. Recently, it has been demonstrated that the soluble form of ICAM-1 has been detected in human serum and has been increased in many other inflammatory or autoimmune disorders. To evaluate the involvement of ICAM-1 in unstable angina, we examined plasma soluble ICAM-1 (sICAM-1) levels in coronary circulation. The plasma sICAM-1 levels in the coronary sinus and aortic root were simultaneously examined in 20 patients with unstable angina, 19 patients with stable exertional angina, and 16 control subjects. The plasma levels of sICAM-1 were measured by enzyme-linked immunosorbent assay. The mean plasma sICAM-1 levels (nanograms per milliliter) both in the coronary sinus and aortic root were significantly higher (p <0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (217+/-14 vs 126+/-8; 120+/-10 in the coronary sinus, 202+/-13 vs 125+/-9; 123+/-10 in the aortic root). Furthermore, the mean value was higher in the coronary sinus than in the aortic root in patients with unstable angina. There were no significant differences in the values between in the coronary sinus and aortic root in patients with stable exertional angina and control subjects. Thus, sICAM-1 release is increased, especially in coronary circulation in unstable angina.

Comparison of thrombolytic therapies with mutant tPA (lanoteplase/SUN9216) and recombinant tPA (alteplase) for acute myocardial infarction.

The fibrinolytic capacity of patients with acute myocardial infarction (AMI) is known to be impaired. The primary regulatory element of the fibrinolytic system is plasminogen activator inhibitor (PAI). It has been previously observed that there are 2 peaks in the plasma PAI level of AMI patients at 4h and 16h after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Lanoteplase/SUN9216 is a mutant tPA with a biological half-life longer than that of rtPA. Thrombolytic therapy with mutant tPA or rtPA was carried out consecutively in 21 patients with AMI (8 patients as the mutant tPA group, and 13 patients as the rtPA group). The recanalization time of the mutant tPA group was significantly faster than that of the rtPA group (16.1 +/- 3.9 min vs 39.6 +/- 4.8 min, p<0.01). The PAI activity at 4h after the initiation of thrombolysis was significantly lower in the mutant tPA group than in the rtPA group (8.74 +/- 5.46IU/L vs 26.74 +/- 3.35 IU/L, p<0.01). There was a one mild peak in serial plasma PAI activity levels 24h after the initiation of thrombolysis. The results suggest that thrombolytic therapy with mutant tPA reduced the impairment of fibrinolytic capacity. The mutant tPA gives faster recanalization and lower PAI activity after successful thrombolysis, compared with rtPA.