Purpose Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. Patients and Methods Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible. Patients received oral lenalidomide 25 mg/d continuously until disease progression or unacceptable toxicity. The primary end point was overall response rate; secondary end points included safety, tumor control rate (stable disease or better), time to response, duration of response, time to progression, progression-free survival, and overall survival. Results Objective responses were noted in 11 of 26 patients (overall response rate, 42%; 95% CI, 23% to 63%), including four complete responses and one unconfirmed complete response. The tumor control rate was 73%. The median time to response and duration of response were 1.9 months and not estimable, respectively, and the median time to progression was 3.8 months. The median progression-free survival and overall survival were 3.8 and 20.3 months, respectively. The most frequent grade ≥ 3 adverse events were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%), which were all manageable and reversible. Conclusion Lenalidomide demonstrated clinically meaningful antitumor activity and an acceptable toxicity profile in patients with relapsed or recurrent aggressive ATL, hinting at its potential to become a treatment option. Further investigations of lenalidomide in ATL and other mature T-cell neoplasms are warranted.

This is one of the first prospective reports demonstrating that higher heart rate may predispose to the development of obesity and DM, suggesting that the sympathetic nerve system may play a role in the development of obesity and DM.

High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are strong predictors of atherosclerosis. Statin-induced changes in the ratio of LDL-C to HDL-C (LDL-C/HDL-C) predicted atherosclerosis progression better than LDL-C or HDL-C alone. However, the best predictor of subclinical atherosclerosis remains unknown. Our objective was to investigate this issue by measuring changes in carotid intima-media thickness (IMT). A total of 1,920 subjects received health examinations in 1999, and were followed up in 2007. Changes in IMT (follow-up IMT/baseline IMT × 100) were measured by ultrasonography. Our results showed that changes in IMT after eight years were significantly related to HDL-C (inversely, P < 0.05) and to LDL-C/HDL-C ratio (P < 0.05). When the LDL-C/HDL-C ratios were divided into quartiles, analysis of covariance showed that increases in the ratio were related to IMT progression (P < 0.05). This prospective study demonstrated the LDL-C/HDL-C ratio is a better predictor of IMT progression than HDL-C or LDL-C alone.

Abstract-Aldosterone plays a role in hypertension, and hypertension is prevalent in patients with insulin resistance.Cross-sectional studies have reported that plasma aldosterone levels are higher in patients with insulin resistance. However, it is not known whether plasma aldosterone levels predict the development of insulin resistance. Subjects of the present study were 1235 local residents (490 men and 745 women) who participated in health screenings in Japan in 1999. Plasma aldosterone levels were measured by radioimmunoassay. We investigated the cross-sectional relationship between plasma aldosterone levels and insulin resistance (homeostasis model assessment index Ն1.73 according to the diagnostic criteria used in Japan) in 1088 nondiabetic participants. At the 10-year follow-up, 141 subjects had died, and 260 subjects refused re-examination. We performed a prospective analysis of 564 subjects to predict incident insulin resistance. We found a significant (PϽ0.001) cross-sectional relationship between plasma aldosterone and homeostasis model assessment index at baseline. In the prospective analysis, a significantly higher (PϽ0.05) relative risk ( he most important physiological role of aldosterone is to control water homeostasis and electrolytes balance. High levels of adrenal aldosterone secretion cause hypertension, that is, primary aldosteronism, a well-known form of secondary hypertension. Moreover, high plasma aldosterone levels predict the development of hypertension. 1 In view of the fact that aldosterone is a mineral corticosteroid, the association of aldosterone and hypertension is not doubted. Recently, the association between aldosterone and obesity or insulin resistance has attracted much attention. Experimental evidence suggests an interaction between aldosterone and insulin. 2 Aldosterone induces hypokalemia, which may modulate insulin secretion, has direct effects on insulin receptor function, 3,4 causes pancreatic ␤-cell dysfunction or even apoptosis, 5 interferes with insulin signaling pathways, 6 and decreases insulin sensitivity in human adipocytes in vitro. 7 Moreover, aldosterone reduces the expression of insulinsensitizing factors, such as adiponectin and peroxisome proliferator-activated receptor-␥, in obese, diabetic mice. 8 In addition to the above-mentioned in vitro and animal studies, several clinical studies reported an association between plasma aldosterone levels and insulin resistance. Plasma aldosterone levels are elevated in hypertensive obese subjects. 9 Cross-sectional studies have shown an association between plasma aldosterone levels and insulin resistance in hypertensive and normotensive subjects. 10,11 Moreover, insulin resistance was restored by surgical intervention or mineralocorticoid receptor blocker in primary hyperaldosteronism. 12 However, contradictory results were reported by other investigators showing no difference of glucose metabolism in a relatively small number of subjects with primary hyperaldosteronism and essential hypertension 13 and showing no cha...

This 27-year study in a community-based cohort indicated that DHEAS level may be a predictor of longevity in men, independent of age, blood pressure, and plasma glucose.

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A new factor-independent megakaryoblastic cell line, designated SET-2, was established from the peripheral blood of a patient with leukemic transformation of essential thrombocythemia (ET). SET-2 expressed CD 4, 7, 13, 33, 34, 36, 38, 41, 61, 71, 117, 126, 130 and c-mpl. In addition, it spontaneously produced numerous platelet-like particles in liquid culture. These particles were shown to be the same size as normal platelets, and to express CD 36, 38, 41, 61 and 71. Proliferation of SET-2 was not influenced by thrombopoietin (TPO) and other hemopoietic cytokines. SET-2 was found to express the platelet-specific proteins such as platelet factor 4 and ␤-thromboglobulin. The levels of expression were not altered by TPO. SET-2 also secreted interleukin-6 into the supernatants, as well as normal megakaryocytes. These results suggest that SET-2 spontaneously matures to megakaryocytes and produces platelet-like particles. These findings indicate that SET-2 may be useful for investigating the proliferation and differentiation mechanisms of leukemia cells and the role of c-mpl on megakaryoblasts, megakaryocytes, and platelets in ET. Leukemia (2000) 14, 142-152.

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