Exercise training, postprandial hypertriglyceridemia, and LDL subfraction distribution

The purpose of this study was to examine differences in postprandial hypertriglyceridemia (PP-HTG) and low density lipoprotein (LDL) subfraction distribution among groups of men and women with different fitness levels. Fifty-four men and women (ages 30-53 yr) were recruited based on their previous two-year activity level: sedentary (S), recreational exercisers (R), and endurance trained (T). After a 24-h dietary preparation, blood was collected, and LDL subfractions were separated and analyzed for cholesterol (C) and apoprotein B100. Plasma triglyceride (TG) concentration was assessed before and at 2, 4, 6, and 8 h after fat meal. PP-HTG was significantly higher for the S group compared with the two activity groups. LDL3-C and LDL3-apoprotein B100 were significantly higher for the S group compared with the T group and for men compared with women. These findings suggest that both recreational and competitive aerobic training are associated with a lower TG response after a fatty meal. However, higher volume aerobic training may be necessary to reduce the number of dense LDL molecules and their cholesterol content.     

Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation

Sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate (SPP), are emerging as a new class of second messengers involved in cellular proliferation, differentiation, and apoptosis. Nerve growth factor (NGF), a neurotrophic factor for pheochromocytoma PC12 cells, induced a biphasic increase in the activity of sphingosine kinase, the enzyme that catalyzes the formation of SPP. This activation was blocked by K252a, an inhibitor of tyrosine kinase A (trkA). A rapid 1.7-fold increase was followed by a marked prolonged increase reaching a maximum of fourfold to fivefold stimulation with a concomitant increase in SPP levels and a corresponding decrease in endogenous sphingosine levels. Levels of ceramide, the precursor of sphingosine, were only slightly decreased by NGF in serum-containing medium. However, NGF decreased the elevation of ceramide induced by serum withdrawal. Treatment of PC12 cells with SPP did not induce neurite outgrowth or neurofilament expression, yet it enhanced neurofilament expression elicited by suboptimal doses of NGF. Moreover, SPP also protected PC12 cells from apoptosis induced by serum withdrawal. To further substantiate a role for SPP in the cytoprotective actions of NGF, we found that N, N-dimethylsphingosine, a competitive inhibitor of sphingosine kinase, also induced apoptosis and interfered with the survival effect of NGF. These effects were counteracted by exogenous SPP. Moreover, other structurally related compounds, such as dihydrosphingosine 1-phosphate and lysophosphatidic acid, had no significant protective effects. Our results suggest that activation of sphingosine kinase and subsequent formation of SPP may play an important role in the differentiation and survival effects induced by NGF.     

Treatment results and prognostic factors in 101 men treated for squamous carcinoma of the penis

PURPOSE: This retrospective study was performed to assess the treatment outcome and prognostic factors in 101 men with invasive squamous carcinoma of the penis treated at the Royal Marsden Hospital between 1960-1990. METHODS AND MATERIALS: The tumor was confined to the glans penis (T1) in 79 patients, 82 were node negative (N0), and two patients had distant metastases at presentation. The histology was Grade 1 (G1) in 36, Grade 2 (G2) in 18, Grade 3 (G3) in 28, and unknown in 19 patients. Node-positive disease was commoner in patients with G3 (p = 0.02) or T2/3/4 tumors (p = 0.007). Treatment for the primary tumor was external beam radiotherapy (EBRT) in 59, interstitial brachytherapy in 13, and partial or total penectomy in 29 patients. The median dose, dose/fraction, and treatment time for EBRT was 60 Gy, 2 Gy/fraction, and 46 days, respectively. Eighty patients received no inguinal node treatment, 13 had EBRT (4 with chemotherapy), and 8 underwent groin dissection at presentation. RESULTS: During a median follow-up of 5.2 years (2 months-22 years), 56 patients died (penile cancer 31, intercurrent illness 23 and unknown cause 2), giving 10 year overall and cause-specific survival (CSS) of 39 and 57%, respectively. Adverse prognostic factors for CSS on univariate analysis were G3, ulcerative/fungating or T2/3/ 4 tumors, node positive, Jackson's Stage 2/3/4, and surgical treatment for the primary. All but the last two were significant independent prognostic factors for CSS on multivariate analysis. Penile or perineal recurrence or residual disease after initial treatment was seen in 36 out of 98 evaluable patients, giving a 10-year local failure rate (LFR) of 45%. Local failure after initial treatment was successfully salvaged in the majority (26 out of 36) of patients with further surgery or radiotherapy, and local control was achieved ultimately in 74 out of 77 T1, 7 out of 12 T2; 3 out of 3 T3, and 3 out of 5 T4 tumors. In the 44 evaluable patients with T1 tumors treated by EBRT the only adverse RT parameter approaching prognostic significance (p = 0.052) was a BED value corrected for recovery of <60 Gy (alpha/beta 10, K = 0.5 Gy/day, mean = 21 days). CONCLUSION: Invasive squamous carcinomas of the penis carry a significant risk of loco-regional recurrence after initial radiotherapy and this can be successfully salvaged in most patients with further treatment. This mandates close follow-up to detect loco regional recurrence early.     

A differential scanning calorimetric study of Newcastle disease virus: identification of proteins involved in thermal transitions

The spatial and temporal pattern of expression of enhancer trap lines reporting on the wingless (wg) and engrailed (en) genes was characterized in the adult antenna of Drosophila melanogaster. The time courses of expression seen for wg and en, although different from each other, reveal a complex well-controlled pattern of temporal expression, providing evidence that regulatory mechanisms are preserved throughout the life span of the adult fly. Altering the life span demonstrates that the temporal patterns of expression of both wg and en are linked to life span. These studies suggest that the expression of wg and en in the adult antenna is controlled by age-dependent mechanisms.