Alterations in epithelial glycocalyx of rabbit uteri during early pseudopregnancy and pregnancy,and following ovariectomy

Pseudopregnant, pregnant, and ovariectomized rabbits were utilized to study hormonal mediation of uterine epithelial surface negativity and glycocalyx morphology, and to seek local effects of blastocysts at sites of implantation. A loss of surface negativity [polycationic ferritin (PCF) binding] by day 6 of pregnancy or pseudopregnancy was noted, accompanied by alterations in epithelial glycocalyx. Uteri from estrous animals, or ovariectomized animals receiving oil or estradiol injections, bound PCF and exhibited a “globular” glycocalyx. Uteri from day 6 pseudopregnant or pregnant animals, or ovariectomized animals receiving progesterone injections, did not bind PCF or exhibit a globular glycocalyx. Both PCF binding and the globular character of the epithelial glycocalyx were sensitive to neuraminidase and trypsin treatment, suggesting sialoglycoprotein contribution to surface negativity. Implanting blastocysts had no detectable local effect on surface negativity, but did induce local reduction of epithelial glycocalyx at sites of implantation. Results of this study suggest that uterine epithelial glycocalyx alterations during the preimplantation period reflect a general response to prosgesterone stimulation, primarily qualtitative in nature, related to the acquisition of receptivity to ovo-implantation.     

Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training

Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. To explore the role of protein synthesis in the trial spacing effect, we assessed the protein synthesis dependence of hippocampal LTP induced by 100-Hz tetraburst stimulation delivered to mouse hippocampal slices in either a temporally massed (20-s interburst interval) or spaced (5-min interburst interval) fashion. To extend our studies to the behavioral level, we trained mice in fear conditioning using either a massed or spaced training protocol and examined the sensitivity of long-term memory to protein synthesis inhibition. Larger LTP was induced by spaced stimulation in hippocampal slices. This improvement of synaptic potentiation following temporally spaced synaptic stimulation in slices was attenuated by bath application of an inhibitor of protein synthesis. Further, the maintenance of LTP induced by spaced synaptic stimulation was more sensitive to disruption by anisomycin than the maintenance of LTP elicited following massed stimulation. Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.     

ASO Author Reflections: National Analysis of Breast Surgery Malpractice Cases: A Teachable Moment?

Annals of Surgical Oncology -     

Tumor suppressor genes,growth factor genes,and oncogenes in hepatitis B virus-associated hepatocellular carcinoma

A series of changes in the genes that control hepatocyte growth, or interference with the protein products of these genes, appears to have an important role in the etiology of hepatocellular carcinoma (HCC). Mutations of the p53 tumor suppressor gene have been identified in 30-50% of HCC patients in some geographic areas. Abnormalities of the RB tumor suppressor gene have been found in 20-25% of HCCs, including 80-86% of HCCs with p53 mutations. Overexpression of transforming growth factor α (TGF-a), insulin-like growth factor II (IGF-II), and the oncogenes N-ras, c-myc, and c-fos have been found in high percentages of HCC patients. The cumulative effect of these changes may be more important than the order in which they occur. Some of these changes may explain the mechanism(s) by which the hepatitis B virus participates in the development of HCC. © 1994 Wiley-Liss, Inc.     

Uptake of planar polychlorinated biphenyls and 2,3,7,8-substituted polychlorinated dibenzofurans and dibenzo-p-dioxins by birds nesting in the lower fox river and Green Bay,Wisconsin, USA

The uptake of persistent polychlorinated hydrocarbons (PCHs) by four avian species was investigated at upper trophic levels of two aquatic food chains of the lower Fox River and Green Bay, Wisconsin. Accumulation of total and specific planar polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), polychlorinated dibenzo-p-dioxin (PCDDs), and H411E rat hepatoma cell bioassay-derived 2,37,8-tetrachlorodibenzop-dioxin equivalents (TCDD-EQ) was evaluated in Forster's tern (Sterna forsteri) and common tern (Sterna hirundo) chicks, and in tree swallow (Tachycineta bicolor) and red-winged blackbird (Agelaius phoeniceus) nestlings from colonies nesting in several locations within the watershed. Concentrations of the PCHs were greatest in eggs and chicks of the two tern species, less in the tree swallows and least in the red-winged blackbirds. Young of all four species accumulated total PCBs, PCB congeners 77, 105, 126, and 169, and TCDD-EQ. The young birds also accumulated small concentrations of several 2,3,7,8-sbustituted PCDF and PCDD congeners. Uptake rates for certain of the PCHs for the Forster's tern chicks were: 15 g/day for total PCBs, 70, 200, 6.5, and 0.14 ng/day for PCB congeners 77, 105, 126, and 169, respectively, and 270 g/day for TCDD-EQ. Principal components analysis revealed that the patterns of PCH concentrations in the samples were influenced by species of bird, their age (or length of exposure) and nesting location. Collectively, our findings demonstrate that exposure of avian species to contaminants derived from aquatic food chains can be characterized and quantified for the purposes of ecological risk assessment.     

Research utilization models: frameworks for implementing evidence-based occupational therapy practice

Evidence-based practice is an important step in the professional evolution of occupational therapy and also provides the means for state-of-the-art innovative clinical service for clients. An essential step in incorporating innovations and developments into clinical practice is through research utilization. Nine models of research utilization developed in the literature are reviewed and critiqued. These are: (1) the Conduct and Utilization of Research in Nursing (CURN) Project; (2) the Stetler-Marram Model; (3) the University of North Carolina Approach; (4) the Innovation Diffusion Process Model; (5) Killeen's Matrix of Research Activity; (6) the Iowa Model of Research In Practice; (7) the Western Interstate Commission for Higher Education In Nursing Project; (8) the Nursing Child Assessment Satellite Training Project; and (9) the Linkage Model. Research utilization models provide a framework for collaboration and the necessary conditions for research utilization activities to be successful. Copyright © 1999 Whurr Publishers Ltd.     

Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data

Summary Two patients presenting with malignant meningitis resulting from small-cell carcinoma of the lung and with lymphoblastic leukemia, respectively, were treated by intrathecal administration of etoposide. In both cases, this treatment was well tolerated and produced relief of the central nervous system symptoms. Pharmacokinetic data showed that cerebrospinal fluid drug levels of up to 5.2 g/ml were achieved, which were considerably higher than those obtained after i.v. administration of high-dose etoposide.     

Three-dimensional computed tomography

Three-dimensional images were generated by reformating data from an axial image set. Separate contours were generated for bone and for tumor. The contour representing the tumor was generated by tracing the tumor using a cursor on the CRT. The contours showed the relationship of the tumor to the skull base. Three-dimensional imaging by this method is more of a communication tool than a diagnostic tool. The information on such images can be derived from close analysis of the axial image set. Indeed, determination of the position of the tumor relative to very precise structures requires analysis of the original images. The three-dimensional imaging does orient the observer and give an overall view of the position of the tumor. Because the contour of the tumor is traced, the final image represents the opinion of the radiologist. Various technical considerations and artifacts are discussed.     

The response of ataxia-telangiectasia homozygous and heterozygous skin fibroblasts to neocarzinostatin

Skin fibroblast strains from patients with ataxia-telangiectasia(A-T) were recently reported to be hypersensitive to the antitumorantibiotic neocarzinostatin (NCS). In this study, the distinctintermediate degree of NCS sensitivity previously shown withtwo strains of A-T heterozygous fibroblasts was extended andconfirmed in an additional eight strains. A sensitivity baselinefor A-T heterozygous cells has thus been established and mayserve for the laboratory diagnosis of A-T heterozygotes, a cancer-pronepopulation. The response of A-T homozygous and heterozygouscells to NCS was further characterized by two molecular parameters,DNA repair synthesis and inhibition of DNA replication. Thepattern of dose response with regard to DNA repair synthesis,as assayed by the benzoylated naphthoylated DEAE cellulose chromatographymethod, was similar in normal, A-T homozygous and A-T heterozygouscells, although certain variability between strains was observedwith regard to the amount of repair incorporation. This findingcorrelates with a similar observation made with the same cellstrains following -irradiation. Inhibition of DNA synthesisfollowing NCS treatment was reduced in A-T homozygous cells,as compared to normal cells, but the "Inhibition resistant"component of DNA synthesis typically observed following treatmentwith low doses of X-rays or bleomycin was not observed withNCS. A-T heterozygous cells showed somewhat less inhibitionof DNA synthesis than normal cells following NCS treatment,although this difference was small and was not significant enoughto serve as an additional laboratory diagnostic aid. It is concludedthat the reduced inhibition of DNA synthesis, rather than reducedextent of DNA repair synthesis, correlates with the cellularhypersensitivity of A-T homozygous cells. This hypersensitivityseems to be observed primarily, if not exclusively, with DNAbreaking agents.