Citations

AbstractTo evaluate long‐term survival of patients with gastrointestinal carcinoid tumors and to assess factors that may influence prognosis, 154 patients (49% females, 51% males), median age 62 years (range 12–84 years) treated at our institution during 1972–1982 have been followed long term. Tumor location included the foregut (7%), midgut (62%), and hindgut (30%). Ninety‐five percent of the patients underwent surgical or endoscopic excision of the primary tumor, with overall operative mortality and postoperative morbidity rates of 2.6% and 11%, respectively. At follow‐up, 60 patients (39%) were alive (median follow‐up 18 years; range 1–26 years). The main causes of death included carcinoid tumor burden (32%), unrelated causes (45%), other malignancy (19%), and unknown causes (4%). Observed overall 5‐ and 10‐year survivals were 69% and 53%, respectively. Survival was not related to gender or symptoms at presentation. However, age, embryologic origin, tumor size, depth of invasion, nodal status, and stage of disease proved to be of statistical significance (log‐rank). In a multivariate Cox' model, only older age (> 62 years) [P =0.001, odds ratio (OR) = 3.4) and embryologic origin (midgut versus foregut) (P = 0.045, OR = 0.45) provided independent prognostic power when death from any cause was taken as the end‐point. This study confirms that patient's age and the site of the primary tumor have prognostic significance. Carcinoid tumors are neuroendocrine tumors with a relatively good prognosis, and long‐term survival is possible despite advanced stages of disease.

AbstractAnagrelide is a novel platelet-lowering agent that has recently been approved for use in essential thrombocythemia (ET) and related disorders. Short-term drug efficacy and toxicity data have previously been presented. The purpose of this study was to obtain additional information regarding long-term anagrelide use. This is a retrospective series of 35 young patients (17 to 48 years) with ET who received anagrelide treatment before 1992. Initial drug dosage ranged between 1 and 10 mg/d, and the median maintenance dosage was 2.5 mg/d. The overall initial response rate of 94% included 74% complete remissions and 20% partial remissions. Of the 33 responding patients, 27 (82%) remained on anagrelide therapy for a median of 10.8 years (range, 7 to 15.5). Of these, 66% maintained a complete and 34% a partial remission over the study period. In general, the reporting of somatic side effects decreased over time, and anemia was the only new side effect that emerged after long-term therapy. Eight patients (24%) experienced a more than 3 g/dL decrease in hemoglobin level. Despite active therapy, 20% of the patients experienced a total of 10 thrombotic episodes, and a similar proportion experienced major hemorrhagic events. All thrombohemorrhagic complications occurred at a platelet count of more than 400 × 109/L. It is concluded that long-term treatment of ET with anagrelide is associated with decreased reporting of initial side effects and the development of mild-to-moderate anemia. Complete normalization of platelet counts may be needed to minimize residual thrombohemorrhagic risk during therapy.

ABSTRACTThe role of NF-κB in the reactivation of human immunodeficiency virus (HIV) from latency in CD4 T lymphocytes is well documented. However, its role in driving HIV transcription in human macrophages, which contain a constitutive nuclear pool of NF-κB, is less well understood. In this study we have investigated the role that the constitutive pool of NF-κB and the NF-κBcis-acting motifs of the HIV long terminal repeat (LTR) play in regulating HIV transcription in human monocytic cells and primary macrophages. Inhibition of the constitutive nuclear pool of NF-κB (RelA and RelB) in the promonocytic U937 cell line using dominant-negative IκBα significantly decreases HIV replication. Moreover, it is demonstrated that in the differentiated monocytic cell line THP1, which contains a constitutive nuclear pool of NF-κB (RelB),an HIV provirus containing mutations of the κBcis-acting sites in the LTR is transcriptionally impaired. Reduction of the constitutive pool of NF-κB in human macrophages by an adenovirus vector expressing a dominant-negative IκBα also reduces HIV transcription. Lastly, mutation of the NF-κBcis-acting sites in the LTR of an R5 HIV provirus completely abrogates the first cycle of HIV transcription. These studies indicate that thecis-acting NF-κB motifs of the HIV LTR are critical in initiating HIV transcription in human macrophages and suggest that the constitutive nuclear pool of NF-κB is important in regulating HIV transcription in these cells.

An optical spin micromotor operated by optical tweezers, described in the present study, converts radiant energy directly to mechanical energy. This conversion is of great practical and fundamental interest. The optical spin micromotor consists of a two-bead linkage. The large bead (2.0 μm in diameter) is trapped by the optical tweezers and rotates around the laser beam axis. The small bead (0.94 μm in diameter) is partially coated with gold/palladium for generating the spin torque through the change of momentum from gradient radiation pressure of the same laser applied on the coated small bead. With a laser power of 29 mW at the sample plane, the spin speed averaged 158.8±155.5 rpm (mean±standard deviation) and the torque was estimated as 101.9±99.8 pN nm. This optical spin micromotor will be useful in (1) providing a fundamental step toward developing optical-operated mechanical devices, (2) twisting macromolecules, and (3) generating vortex and shear force in medium at nanoscale.

Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficiency with severely impaired FAO. Matings between LCAD +/− mice yielded an abnormally low number of LCAD +/− and −/− offspring, indicating frequent gestational loss. LCAD −/− mice that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria. Approximately 10% of adult LCAD −/− males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD −/− mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo .