The modulation of cellular responses to poly(2-hydroxyethyl methacrylate) hydrogel surfaces: phosphorylation decreases macrophage collagenase production in vitro

We examined the regulation of collagenase production by the monocyte/macrophage THP-1 cell line when these cells were exposed to poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel surfaces with different chemistries and morphologies. Tissue culture modified polystyrene (TCP), used as a control surface, induced the maximum collagenase response. Copolymer hydrogels containing 2-ethoxyethyl methacrylate (EMA) or methyl methacrylate (MMA) also induced a high response, while PHEMA hydrogels induced a low level response and the phosphorylated hydrogel induced no response. This pattern was altered when the morphology of the hydrogels was changed to that of a sponge. The overall enzyme response to the sponge hydrogels was lower than that to the homogeneous hydrogels. Sponges containing EMA and MMA produced low level response relative to the TCP control. PHEMA and phosphorylated sponges produced little and no response respectively. The dramatically reduced enzyme response to phosphorylated surfaces was not a consequence of cell death, and may be a phenomenon related to changes in cell surface charge.     

Pathologic seminal vesicle invasion after radical prostatectomy for patients with prostate carcinoma: effect of early adjuvant radiation therapy on biochemical control

BACKGROUND: The authors evaluated the effect of postoperative radiation therapy on freedom from biochemical failure (bNED) in men with prostate carcinoma who had pathologic seminal vesicle invasion after radical prostatectomy and negative pelvic lymph node dissection (pT3cN0). METHODS: Between 1989 and 1995, 375 men underwent radical prostatectomy at Thomas Jefferson University Hospital. Fifty-three men (13%) had pT3cN0 prostate carcinoma and were the subject of this analysis. Men in whom prostate specific antigen (PSA) could not be detected were deemed free of biochemical failure. RESULTS: Of the 53 men with pT3cN0 prostate carcinoma, 18 had an elevated PSA immediately after surgery and received salvage radiation therapy (RT). The 3-year bNED rate for this group was only 38%. At 3 months, PSA could not be detected in the other 35 men. Fifteen of those 35 men underwent early adjuvant RT, and the other 20 were observed for biochemical failure. The 3-year bNED rate for the 15 patients treated with immediate adjuvant RT was 86%, compared with 48% for the 20 men who were observed (P = 0.01). CONCLUSIONS: These data suggest that early adjuvant RT for men with pT3cN0 prostate carcinoma and no detectable PSA postoperatively reduces the likelihood of future biochemical failure. Men with pT3cN0 prostate carcinoma and a persistently elevated postoperative PSA level are less likely to benefit from RT and should be considered for systemic therapy.     

Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding proteins

Ndr is a nuclear serine/threonine protein kinase that belongs to a subfamily of kinases identified as being critical for the regulation of cell division and cell morphology. The regulatory mechanisms that control Ndr activity have not been characterized previously. In this paper, we present evidence that Ndr is regulated by EF-hand calcium-binding proteins of the S100 family, in response to changes in the intracellular calcium concentration. In vitro, S100B binds directly to and activates Ndr in a Ca2+-dependent manner. Moreover, Ndr is recovered from cell lysates in anti-S100B immunoprecipitates. The region of Ndr responsible for interaction with Ca2+/S100B is a basic/hydrophobic motif within the N-terminal regulatory domain of Ndr, and activation of Ndr by Ca2+/S100B is inhibited by a synthetic peptide derived from this region. In cultured cells, Ndr is rapidly activated following treatment with Ca2+ ionophore, and this activation is dependent upon the identified Ca2+/S100B-binding domain. Finally, Ndr activity is inhibited by W-7 in melanoma cells overexpressing S100B, but is unaffected by W-7 in melanoma cells that lack S100B. These results suggest that Ndr is regulated at least in part by changes in the intracellular calcium concentration, through binding of S100 proteins to its N-terminal regulatory domain.     

Limiting the possibility of progressive collapse

The chance of progressive collapse is not confined to panel-frame buildings, though the latter may be more exposed to the danger. The following statement is issued by CIB Working Commission W23A on loadbearing walls and accordingly deals with the subject in the context of loadbearing walls. Professor Lewicki is based at the Centre for Building Systems Research and Development, Warsaw, and Professor Olesen at the Danish Engineering Academy.     

Sarcoidosis and thyrotoxicosis: A study of five patients

Regional blood flow of the gastrointestinal (GI) tract and cardiac output have been determined in male Sprague-Dawley rats weighing from 30-726 g. The cardiac output (ml/min per kg) was highest in rats weighing 80-100 g. In heavier rats the cardiac output decreased proportionally with the body weight. The gradient of blood flow to the different parts of the GI tract develops step by step. In the weaning period the blood flow (ml/min per g tissue) through the stomach was less than that through the distal parts of the GI tract. However, the blood flow through the small intestine, cecum and large intestine was uniform at this age. In rats weighing 80-100 g the blood flow through both the cecum and large intestine was less than that through the small intestine. The gradient in blood flow through the various segments of small intestine developed last.     

A method for diagnosing multiple diseases in MUNIN

A new method for diagnosing multiple diseases in large medical decision support systems based on causal probabilistic networks is proposed. The method is based on characteristics of the diagnostic process that we believe to be present in many diagnostic tasks, both inside and outside medicine. The diagnosis must often be made under uncertainty, choosing between diagnoses that each have small prior probabilities, but not so small that the possibility of two or more simultaneous diseases can be ignored. Often a symptom can be caused by several diseases and the presence of several diseases tend to aggravate the symptoms. For diagnostic problems that share these characteristic, we have proposed a method that operates in a number of phases: in the first phase only single diseases are considered and this helps to focus the attention on a smaller number of plausible diseases. In the second phase, pairs of diseases are considered, which make it possible to narrow down the field of plausible diagnoses further. In the following phases, larger subsets of diseases are considered. The method was applied to the diagnosis of neuromuscular disorders, using previous experience with the so-called MUNIN system as a starting point. The results showed that the method gave large reductions in computation time without compromising the computational accuracy in any substantial way. It is concluded that the method enables practical inference in large medical expert systems based on causal probabilistic networks.     

Partition noise in semiconductor lasers under CW and pulsed operation

A numerical model which simulates the mode partition noise in semiconductor lasers under CW as well as pulsed operation is presented. The noise levels in the individual modes under CW operation are in agreement with those predicted by an analytic small-signal model. Under simulated pulse modulation with pulse repetition frequencies of 633 MHz and 2.2 GHz, the probability density functions for the relative photon numbers in the individual modes are found. The data allow for an evaluation of the mode partition parameterk. For the central modes,kfactors are in the range of 0.31-0.42, depending on bias level and modulation frequency. Weaker side modes carrying less than 5 percent of the total output havekfactors smaller than 0.16.