Growth factors in expressed prostatic fluid from men with prostate cancer, BPH, and clinically normal prostates.

BACKGROUND: Although growth factors such as epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, and TGF-beta are important regulators of prostate cell growth in vitro and in animal models, evidence to support their role in human prostate cancer development remains sparse. We previously showed that men without prostate cancer have concentrations of EGF and TGF-alpha in expressed prostatic fluid (EPF) that are individually distinct and stable over time. This study addressed whether growth factor levels in EPF are associated with the presence or progression of prostate cancer. METHODS: We measured levels of immunoreactive EGF, TGF-alpha, and TGF-beta1 in stored EPF samples from three age-matched groups: 19 men with untreated, histologically diagnosed prostate cancer (CaP), 38 with benign prostate hyperplasia (BPH), and 19 with normal prostate glands (NPD). RESULTS: Median TGF-alpha was lower in the BPH group (0.45 ng/ml) than in either CaP (0.63 ng/ml) or NPD (0.58 ng/ml) groups (P = 0.03 and 0.12, respectively). For EGF, the median was lowest in the CaP group and highest in the NPD group (92.5 ng/ml vs. 175.5 ng/ml, P = 0.006). For TGF-beta1, the median level in CaP was 2.7 times higher than the median level among all controls (6.65 ng/ml vs. 2.46 ng/ml, P = 0.002). Growth factor levels were not associated with tumor stage or Gleason score. However, the single case with distant metastases had TGF-beta1 levels 23-fold higher than the CaP median. CONCLUSIONS: The results suggest that at the time of CaP diagnosis, EGF levels in EPF are significantly lower, and TGF-beta1 levels significantly higher, than normal. Marked overexpression of TGF-beta1 in advanced CaP might be reflected in extremely high EPF levels.

Mitogenic growth factors in breast fluid obtained from healthy women: evaluation of biological and extraneous sources of variability.

Peptide growth factors (GFs), including epidermal GF (EGF) and transforming GF-alpha (TGF-alpha), are presumed to play an important role in the local regulation of breast cell proliferation. Breast fluid collected by nipple aspiration provides a potential means to assess the concentration of these factors in contact with the ductal epithelium. Although identification of immunoreactive EGF-like GFs in breast fluid has been reported previously, we performed this study to evaluate the sensitivity and reliability of newer RIA methods and to characterize the sources and amounts of both intra- and intersubject variability. We also evaluated the relationship of breast fluid EGF and TGF-alpha levels to each other and to plasma levels of estradiol and progesterone. Breast fluid and plasma samples were obtained two to four times at weekly intervals from 18 healthy, premenopausal women. EGF and TGF-alpha were measured by competitive binding RIA. Both GFs were detected with good precision in all breast fluid samples analyzed, using dilutions as low as 1:100 for EGF (1 microliter) and 1:25 for TGF-alpha (4 microliters). The correlations between the right and left breasts, sampled concurrently, were r = 0.78 (P = 0.003) for EGF and r = 0.89 (P = 0.0001) for TGF-alpha. For both GFs, the variation between women was substantially greater than the variation between breasts or over time in an individual woman, particularly for EGF, for which there were 100-fold differences between women in mean levels. When samples from multiple women were analyzed together, we found no apparent relationships between EGF and TGF-alpha levels or between either GF level and menstrual cycle phase or plasma hormone concentrations. However, in random effects analyses, EGF levels within an individual were significantly associated overall with both TGF-alpha (P = 0.02) and plasma estradiol levels (P = 0.01). These data, which are the first comprehensive results on the feasibility of measuring mitogenic GFs in breast fluid, support the conclusion that women secrete consistent and individually distinct levels of EGF and TGF-alpha and that, in at least some women, EGF secretion in vivo covaries with both TGF-alpha in breast fluid and circulating estradiol.

A re-examination of sex differences in axon density and number in the splenium of the rat corpus callosum.

Previous work from our laboratory reported a sex difference in axon number in the splenium of the adult rat corpus callosum. However, the cortical origin of the axons that were sampled is unknown and sex differences may exist in the topography of axons in this area. The present study revisits the issue of sex differences in axon number in the splenium. First, the topographical organization of axons in the splenium was investigated. Rats each received single intracortical injections of horseradish peroxidase (HRP). The location of HRP labelled fibers in the corpus callosum was compared across the various injection sites. There is a rostrocaudal organization of axons in the splenium based on rostral to caudal cortical location that does not vary by sex. Second, visual axons, which comprise the posterior fifth (relative to overall length) of the corpus callosum in both sexes, were thoroughly sampled with electron microscopy. Significant dorsoventral and rostrocaudal variation in myelinated and unmyelinated axon density was found. While axon density varied to some extent depending on the sex of the animal, axon number calculations revealed no sex differences in total axon number. Males, however, had significantly more myelinated axons than females. Thus, sex differences in axon density in the adult rat splenium were regional and did not result in overall sex differences in axon number.

Salivary alpha-amylase as a measure of endogenous adrenergic activity.

This investigation was designed to evaluate the production rates and concentrations of salivary alpha-amylase as a measure of adrenergic activity under several conditions of stress in human subjects. Saliva and blood samples were simultaneously collected from men at four 15 min intervals both before and after regimens for exercise, a written examination, or a rest period. The regressions of salivary alpha-amylase on plasma norepinephrine (NE) concentrations were significant for both exercise (P < 0.001) and examination (P < 0.01) protocols. Aerobic exercise induced a 3-fold mean increase in alpha-amylase; both NE and epinephrine (EP) increased approximately 5-fold over control levels. Levels of alpha-amylase and NE returned to control levels within 30-45 min after exercise, but EP remained elevated by approximately 2-fold during the remaining hour of observation. During the written examination, alpha-amylase and NE, but not EP, concentrations increased in parallel. In further studies the effects of exercise and exposure to heat and cold on the relationship of salivary alpha-amylase to heart rate and body temperature were investigated. Greater intensities of exercise were associated with greater increases in alpha-amylase concentrations. During heat exposure in a sauna (66 degrees C for 40 min) amylase, heart rate and body temperature all increased progressively. However, during exposure to cold (4 degrees C for 40 min) amylase increased rapidly, though heart rate and body temperature remained unchanged. Salivary cortisol concentrations were unchanged during exposure to heat or cold. We conclude that salivary alpha-amylase concentrations are predictive of plasma catecholamine levels, particularly NE, under a variety of stressful conditions, and may be a more direct and simple end point of catecholamine activity than are changes in heart rate.

Splenic regeneration and phagocytic function after partial splenectomy in baboons.

Total splenectomy, especially in children, results in diminished ability to combat infection by capsulated bacteria. It is, however, uncertain how much splenic tissue is needed to maintain this ability. In this experimental study on baboons, in situ remnants after partial splenectomy were examined to evaluate regeneration and phagocytic function after injection of dual-labelled liposomes into their splenic arterial supply. The results showed that resection of as much as two-thirds of the spleen in baboons allowed sufficient regeneration to support adequate macrophage phagocytic function.

Combined use of alpha-fetoprotein and ultrasound in the prenatal diagnosis of arteriovenous fistula in the brain.

A case of arteriovenous fistula in the brain detected by the combined use of maternal serum alpha-fetoprotein (AFP) and ultrasound in the third trimester of pregnancy is described. The maternal serum AFP concentration at 34 weeks of gestation was 300 ng/mL (2.3 times the median). Stage II diagnostic ultrasonography at 37 weeks revealed a large midline cystic mass, contiguous to a normal-appearing lateral ventricle and surrounded by an abnormal heterogeneous zone of increased echogenicity. At birth, the cord blood AFP concentration was 2 SD above the mean. Subsequent histopathologic examination revealed a vein of Galen aneurysm and fistula in the brain.