The Robert Wood Johnson Foundation

Eleven patients with active unicameral bone cysts were treated primarily with placement of demineralized bone matrix in the cyst by using a two-needle technique and a custom large-bore needle. Cyst healing was rated according to the Neer classification, and the average time of healing was 4.5 months. The demineralized bone matrix demonstrated an ability to obliterate the cyst in nine of 11 patients by using a single injection within 4-5 months, and at 2 years' follow-up, no cysts were deemed active or recurrent.     

Modelling cortical cataractogenesis. XXIX. Calpain proteolysis of lens fodrin in cataract

The relation between cataract and calpain proteolysis of lens fodrin was studied in two systems: elevated glucose (55.6 mM, diabetic model), and cytochalasin D (CD, 10(-2) mM, actin depolymerization-induced opacity model). Glucose treatment (48 h) caused a visible opaque layer and enzyme leakage, with a concomitant accumulation of ([Ca2+]i) around the lens equatorial cortex. CD caused both earlier and greater opacity and enzyme leakage than glucose. Lens fodrin digestion occurred in parallel with the timing and extent of calcium elevation. A calpain inhibitor peptide (CIP, 10(-2) mM) reduced the proteolysis of fodrin, opacity, and enzyme leakage in glucose-treated lenses but only partially retarded them in CD-treated lenses. These results suggest a mechanism in which calpain proteolysis of fodrin is a critical event in lens damage during opacification of cortical cataract.     

Electropolymerization of pyrrole and immobilization of glucose oxidase in a flow system: influence of the operating conditions on analytical performance

The in situ potentiostatic electropolymerization of pyrrole (Py) on a Pt electrode in a thin-layer amperometric cell and the entrapment of the enzyme glucose oxidase (GOx) for the determination of glucose are reported. Polypyrrole (PPy) is directly formed by continuous passage of a buffered solution of the monomer (0.4 M) and enzyme (250 U mL-1) at pH 7 at a flow rate of 0.05-0.1 mL min-1 under a constant applied potential of +0.85 V vs Ag/AgCl decreases. The electrosynthesis of PPy by injection of 500 microL of a Py + GOx solution in a carrier electrolyte consisting of 0.05 M phosphate buffer and 0.1 M KCl at pH 7.0 was also assayed. The influence of the electropolymerization conditions on the analytical response of the sensor to glucose was investigated. The analytical performance of the PPy/GOx sensor was also studied in terms of durability and storage life, as well as selectivity against electroactive species such as ascorbic acid and uric acid as a function of the thickness of the polymer film formed.     

Expression of multiple cadherins and catenins in the chick optic tectum

Cadherins form a large family of homophilic cell adhesion molecules that are involved in numerous aspects of neural development. The best-studied neural cadherin, N-cadherin, is concentrated at synapses made by retinal axons in the chick optic tectum and is required for the arborization of retinal axons in their target (retinorecipient) laminae. By analogy, other cadherins might mediate arborization or synaptogenesis in other tectal laminae. Here we consider which cadherins are expressed in tectum, which cells express them, and how their expression is regulated. First, using N-cadherin as a model, we show that synaptic input regulates both cadherin gene expression and the subcellular distribution of cadherin protein. Second, we demonstrate that N-, R-, and T-cadherin are each expressed in distinct laminar patterns during retinotectal synaptogenesis and that N- and R- are enriched in nonoverlapping synaptic subsets. Third, we show that over 20 cadherin superfamily genes are expressed in the tectum during the time that synapses are forming and that many of them are expressed in restricted groups of cells. Finally, we report that both beta-catenin and gamma-catenin (plakoglobin), cytoplasmic proteins required for cadherin signaling, are enriched at synapses and associated with N-cadherin. However, beta- and gamma-catenins are differentially distributed and regulated, and form mutually exclusive complexes. This result suggests that cadherin-based specificity involves multiple cadherin-dependent signaling pathways as well as multiple cadherins.     

Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study

BACKGROUND: Large international variations in rates of prostate cancer incidence and mortality suggest that environmental factors have a strong influence on the development of this disease. The purpose of this study was to identify predictive variables for prostate cancer mortality in data from 59 countries. METHODS: Data on prostate cancer mortality, food consumption, tobacco use, socioeconomic factors, reproductive factors, and health indicators were obtained from United Nations sources. Linear regression models were fit to these data. The influence of each variable fit in the regression models was assessed by multiplying the regression coefficient b by the 75th (X75) and 25th (X25) percentile values of the variable. The difference, bX75 - bX25, is the estimated effect of the variable across its interquartile range on mortality rates measured as deaths per 100000 males aged 45-74 years. Reported P values are two-sided. RESULTS: Prostate cancer mortality was inversely associated with estimated consumption of cereals (bX75 - bX25 = -7.31 deaths; P = .001), nuts and oilseeds (bX75 - bX25 = -1.72 deaths; P = .003), and fish (bX75 - bX25 = -1.47 deaths; P = .001). In the 42 countries for which we had appropriate data, soy products were found to be significantly protective (P = .0001), with an effect size per kilocalorie at least four times as large as that of any other dietary factor. Besides variables related to diet, we observed an association between prostate cancer mortality rates and a composite of other health-related, sanitation, and economic variables (P = .003). CONCLUSIONS: The specific food-related results from this study are consistent with previous information and support the current dietary guidelines and hypothesis that grains, cereals, and nuts are protective against prostate cancer. The findings also provide a rationale for future study of soy products in prostate cancer prevention trials.     

Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder

OBJECTIVE: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. METHOD: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. RESULTS: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. CONCLUSIONS: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.     

Increased susceptibility to postoperative sepsis in patients with impaired monocyte IL-12 production

IL-12 is a potent immunoregulatory cytokine that is essential for the development of protective immunity, as demonstrated by numerous animal models of infection. Here, we provide evidence for a critical role of IL-12 in human sepsis. The results of a prospective study of 184 patients undergoing major elective surgery of the upper and lower gastrointestinal tract revealed that, in contrast to patients showing uneventful recovery, monocyte IL-12 production was severely and selectively impaired in patients developing postoperative sepsis. Moreover, the extent of monocyte IL-12 suppression correlated with the severity of postoperative sepsis. Monocyte IL-12 secretion was suppressed before surgery and remained low until the onset of sepsis. Therefore, the suppression of IL-12 secretion preceded the onset of postoperative sepsis but did not occur as a consequence of major surgery. In contrast, IL-1beta production was only reduced during the late postoperative course in patients developing postoperative sepsis, and TNF-alpha release was even increased at different time intervals before the onset of sepsis. Thus, reduced IL-12 release does not reflect a general defect in monocyte cytokine production. Consequently, these results establish a critical role for IL-12 in early resistance to postoperative infection and may allow for the development of novel therapeutic strategies designed to stimulate host defense mechanisms and to reduce the incidence and severity of septic complications.     

The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint

OBJECTIVE: To study the interaction of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) in promoting cartilage collagen destruction. METHODS: Bovine, porcine, and human cartilage and human chondrocytes were studied in culture. The levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were measured by ELISA. RESULTS: When combined with OSM, IL-1alpha, IL-1beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartilage. OSM was the only member of the IL-6 family to have this effect. Human tendon also responded to IL-1alpha and OSM. OSM increased the production of MMP-1 and TIMP-1 but when combined with IL-1alpha, synergistically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovial fluids, and confocal microscopy showed that OSM was produced by macrophages in rheumatoid synovial tissue. CONCLUSION: These results highlight an important new mechanism by which there is irreversible loss of collagen from cartilage.