Nanoparticle-enhanced diffraction gratings for ultrasensitive surface plasmon biosensing

Ultrasensitive surface bioaffinity sensors are created by the adsorption of gold nanoparticles onto gold diffraction gratings. An enhanced diffraction obtained in a surface plasmon resonance geometry is observed due to the optical coupling of the planar surface plasmons in the grating to the localized surface plasmons in the gold nanoparticles. As a first example, these nanoparticle grating biosensors are employed to detect unmodified DNA at a concentration of 10 fM.     

Regulation of Dendritic Cell Function by Dietary Polyphenols

Marked changes in socioeconomic status, cultural traditions, population growth, and agriculture have been affecting diets worldwide. Nutrition is known to play a pivotal role in the pathogenesis of several chronic diseases, and the use of bioactive food compounds at pharmacologic doses is emerging as a preventive and/or therapeutic approach to target metabolic dysregulations occurring in aging, obesity-related chronic diseases, and cancer. Only recently have data on the effects of specific nutrients or food on the immune system become available, and studies regarding the human immune system are still in their infancy. Beyond providing essential nutrients, diet can actively influence the immune system. Understanding how diet and nutritional status influence the innate and adaptive arms of our immune system represents an area of scientific need, opportunity, and challenge. The insights gleaned should help to address several pressing global health problems. Recently, biologically active polyphenols, which are widespread constituents of fruit and vegetables, have gained importance as complex regulators of various cellular processes, critically involved in the maintenance of body homeostasis. This review outlines the potential effects of polyphenols on the function of dendritic cells (DCs), key players in the orchestration of the immune response. Their effects on different aspects of DC biology including differentiation, maturation, and DC capacity to shift immune response toward tolerance or immune activation will be outlined.     

Induction androgen deprivation plus prostatectomy for stage T3 disease: failure to achieve prostate-specific antigen-based freedom from disease status in a phase II trial

OBJECTIVES: There is interest in treating prostate cancer with induction androgen deprivation prior to radical prostatectomy. Data on long-term prostate-specific antigen (PSA)-based survival analyses among patients treated with neoadjuvant hormonal therapy (NHT) and prostatectomy are limited. In 1991 we instituted a pilot study for T3 disease based on endorectal coil magnetic resonance imaging (eMRI), mandatory negative laparoscopic nodal dissection prior to hormonal manipulation, and prostatectomy followed by pathologic and PSA-based outcome determinations. METHODS: Of 26 patients, 21 had negative laparoscopic lymphadenectomy followed by 4 months of NHT (leuprolide +/- flutamide) prior to radical prostatectomy. eMRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3-month intervals. Prostatectomy specimens were evaluated by 3-mm whole-mount step sections. RESULTS: Prior to prostatectomy, biochemical response was documented in all patients and downsizing was observed by eMRI in 57%. Pathologic downstaging to a lower stage (T2c or lower) was achieved in 48%. However, the actuarial 3-year freedom from biochemical relapse rate was only 24%. CONCLUSIONS: Using laparoscopy to exclude node-positive patients and 4 months of NHT appears to result in pathologic and initial biochemical evidence of regression. These factors have not translated into improved freedom from biochemical relapse among patients with Stage T3 disease treated with NHT and prostatectomy. Recent data strongly suggest a beneficial effect in patients with clinical T2 disease treated with NHT and radical prostatectomy. The NGT and radical prostatectomy approach appeared to offer no clear advantage when compared with PSA-based benchmarks achieved with conformal irradiation or NHT followed by external beam treatment among patients with clinical T3 disease.     

Technically accurate intracavitary insertions improve pelvic control and survival among patients with locally advanced carcinoma of the uterine cervix

The purpose of this study was to document whether the technical qualities of a brachytherapy application impacts on the outcome of patients with locally advanced cervix cancer treated by definitive irradiation. A previous report from the patterns of care study demonstrated the importance of brachytherapy in the treatment of locally advanced cervix cancer. Locally advanced disease was defined as FIGO stages Ib (if tumor diameter was < or = 4 cm), IIb (if disease was bilateral or involved the lateral aspect of either parametrium), and III. Localization films from 128 patients with locally advanced squamous cell carcinoma of the cervix were reviewed by a radiation physicist and a radiation oncologist with expertise in gynecologic radiotherapy. All patients received external beam irradiation followed by one brachytherapy application (median point A dose = 8040 cGy; range, 4083-10,020 cGy). Brachytherapy parameters assessed were (a) the distance between the right colpostat source and the distal tandem source, (b) the distance between the left colpostat source and the distal tandem source, and (c) the symmetry of colpostat placement. Implants were scored as "ideal" (n = 8) when all three parameters were deemed satisfactory, "unacceptable" (n = 17) when none of the parameters was deemed satisfactory, and "adequate" (n = 41) in all other cases. Significantly improved 5-year local control was seen when comparing ideal and adequate placements to unacceptable placements (68% vs 34%, P = 0.02). A strong trend toward improved 5-year survival was also noted among the group with ideal and adequate implants as opposed to unacceptable implants (60% vs 40%). Multivariate analysis showed that the technical adequacy of the brachytherapy implant was the most important prognostic discriminant of local control. In conclusion, these analyses demonstrate the direct influence of competent technical implant performance on tumor control and even survival. While only a small fraction of implants for cervical cancer are performed poorly in the United States, there is a need for continued emphasis of the principles for proper implant technique.     

Effect of higher radiation dose on biochemical control after radical prostatectomy for PT3N0 prostate cancer

Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive agents that act on many cells of the body, including monocytes. Here we show that a 5-day course of high dose GC therapy differentially affected the CD14++ and the CD14+ CD16+ monocyte subpopulations in 10 patients treated for multiple sclerosis. While the classical (CD14++) monocytes exhibited a substantial increase from 495 +/- 132 to 755 +/- 337 cells/microl, the CD14+ CD16+ monocytes responded with a pronounced decrease from 36 +/- 15 to 2 +/- 3 cells/microl (P < 0.001). In 4/10 patients the CD14+ CD16+ monocytes fell below detection limits (<0.2 cells/microl). This observation was confirmed when the CD14+ CD16+ monocytes were identified by virtue of their low CD33 expression as these cells decreased as well. After discontinuation of GC therapy the CD14+ CD16+ monocytes reappeared and reached normal levels after 1 week. The profound depletion of CD14+ CD16+ monocytes by GC as described here is a novel effect of GC action in vivo and may contribute to GC-mediated immunosuppression. Determination of the number of this monocyte subset may also serve to monitor the effectiveness of GC therapy in patients requiring immunosuppressive treatment.     

Circadian and ultradian variation in pancreatic secretion of meal-fed pigs after weaning

We studied the time structure of pancreatic secretion in two experiments involving seven 6- to 7-wk-old intact male pigs, surgically fitted with a jugular vein catheter for blood sampling, pancreatic catheter, and a duodenal T-cannula for chronic pancreatic juice sampling for 72 h at 30- to 60-min intervals. Pigs were kept in metabolic cages in a regimen of 12 h of light alternating with 12 h of darkness and were fed at 0800, 1500, and 2200 daily a standard diet based on barley, soybean meal, and fish meal. Beginning 4 d after surgical recovery, three 24-h collections of pancreatic juice and blood sampling were begun either at 0700 or 0800 every 2nd d for 5 d. Pancreatic secretion exhibited a pattern characterized by distinct meal-related secretions of the first phase (postprandial), containing large amounts of protein and enzymes (trypsin and chymotrypsin), and by non-food-stimulated secretions of the second phase with less protein and enzymes. During the dark span, the first phase was practically absent; the response of the pancreatic secretion to the 2200 meal was not very pronounced. Apart from the anticipated circadian rhythm demonstrable by single cosinor analysis on a group basis, a prominent 8-h component was almost invariably statistically significant. Moreover, an approximately 3.43-h component was also prominent. These data indicate that pancreatic secretions are circadian periodic and that their response to a standard meal is also circadian-stage dependent. The circadian components may have been free-running because the pigs were adjusting themselves to the changing phase and that resulted in the period being different from exactly 24 h.     

7-year (circaseptennian) patterns in psychology and biology? Comment on Verhulst and Onghena

Nonlinear rhythmometry confirms a pattern of about 7 years, describing the number of births by birth year of quantum fathers reported by Verhulst and Onghena in 1996 and estimates the period to be 6.53 years with a 95% confidence interval overlapping 7 years. Other patterns of about 7 years are found in biology, as shown herein for the mean gonadal weight of an echinoderm (the purple sea urchin) and a mollusk (the black chiton). A number of periodic components with different frequencies, some shown to be genetically anchored, await applications in psychology as well as in other fields of medicine and biology.