Constant infusions of morphine and intakes of sweetened ethanol solution among rats

Previous studies have indicated that injections of small doses of morphine increase rats' intake of solutions containing ethanol when rats have a choice of either water or a solution containing ethanol. In this experiment, rats which were implanted with osmotic pumps that delivered constant infusions of morphine (0.6 mg/kg/hr across 24 days) had elevated daily intakes of ethanol, as compared to controls, from the second day of opportunity to take the alcoholic beverage until the pumps were removed. In addition, half of the rats with pumps infusing morphine also received injections of morphine (1.0 mg/kg) just before the 1.5-hr opportunity to take alcoholic beverage or water every day for 8 days. Across this 8-day period, these rats took a mean of 5.18 g of pure ethanol/kg of body weight (g/kg) during the 1.5-hr opportunity to take the alcoholic beverage. This was reliably more than the mean of 4.02 g/kg that their counterparts (having morphine pumps and receiving injections of saline) took across the same period. These data support the hypothesis that a surfeit of opioidergic ligand may potentiate drinking of alcoholic beverages.     

Meningeal Macrophages Reflect Lymphocytic Choriomeningitis Virus Pathogenic Phenotypes

Intracerebral (i.c.) infection of adult mice with lymphocytic choriomeningitis (LCM) virus can result in acute lethal central nervous system (CNS) disease which is the result of the host's thymus-derived lymphocyte (T cell) response against the virus. Whether the specific effector function of the T cell is that of a cytotoxic cell (Tc) or a delayed-type hypersensitivity cell (Td) is still under debate. We assumed that if Td cells were important in pathogenesis then accessory cells in the brain (specifically, glass-adherent macrophages) might vary with the outcome of i.c. infection. We found that accumulation of macrophages in the brain (washed from meninges and skull cap) appeared to be independent of the severity of the infection (controlled by the mouse strain as well as the strain and dose of virus used). However, differentiation of macrophages was clearly linked to whether or not the infection caused rapid death. In mice that were destined to survive, macrophages became large, extensively vacuolated, and phagocytically active. In lethally-infected mice macrophages were small and had poor phagocytic abilities. At present this dichotomy could be viewed as either a cause or a consequence of disease outcome. However, the data are not inconsistent with the hypothesis that Td lymphocytes may be of primary importance in pathogenesis.     

N-methylcarbamate derivatives of ellipticine and olivacine with cytotoxic activity against four human lung cancer cell lines.

A series of analogues of the antitumor alkaloids ellipticine and olivacine were tested for cytotoxicity against four human lung cancer cell lines: H69, N417, H460, and H358. Adriamycin (doxorubicin), ellipticine, olivacine, and celiptinium were used as standards. Adriamycin was cytotoxic at 2 microM and celiptinium was inactive at the highest concentrations tested (IC50 > 48 microM). N-methylcarbamates of 9-methoxy-6H-pyrido[4,3-b]carbazole 1-,5-, and 11-methanols gave IC50 values ranging from 0.02 to 0.11 microM against N417, H460, and H358 and were only slightly less effective against H69.     

Arenaviruses: Cellular Response to Long-Term In Vitro Infection with Parana and Lymphocytic Choriomeningitis Viruses

Persistent infections were established in suspension cultures of BHK21/13S cells with both Parana and lymphocytic choriomeningitis viruses. Four generations after infection with either virus, more than 90% of the cells scored as infective centers, with concomitant peaks in extracellular virus yields. In both cultures the synthesis of detectable plaque-forming units (PFU) ceased about the 50th generation postinfection, and this condition was maintained until the 350th cell generation when the cultures were discontinued. The generation time of each culture was identical to that of uninfected parent controls, and at no time were cytopathic effects evident. In spite of the absence of infectivity, over 90% of the cells sampled at various times contained viral antigen demonstrable by immunofluorescence. When either of these persistently infected cell lines was substituted for normal cells in the standard plaque assay, very low efficiencies of plating were observed for homotypic and heterotypic viruses. Plaque formation by several heterologous viruses was virtually unaffected. The mechanism of homotypic plaque exclusion in both cell lines was shown to occur beyond the virion adsorption stage. The original infecting virus genome persisted in both cell lines after standard virus was no longer detectable. This was shown with the lymphocytic choriomeningitis virus-infected cells after storage in liquid nitrogen. After thawing, such cells were found to synthesize standard virus for a brief period. Although the Parana virus-infected cells did not behave this way, the growth medium from these cells would initiate PFU synthesis in normal cells within 36 hr after infection.     

Micropatterned surfaces modified with select peptides promote exclusive interactions with osteoblasts

Microcontact printing techniques were used to pattern circles (diameters 10. 50, 100, and 200 microm) of N1[3-(trimethoxysilyl)-propyl]diethylenetriamine (DETA) surrounded by octadecyltrichlorosilane (OTS) borders on borosilicate glass, a model substrate. The DETA regions were further modified by immobilization of either the cell-adhesive peptides Arginine-Glycine-Aspartic Acid-Serine (RGDS) and Lysine-Arginine-Serine-Arginine (KRSR) or the non-adhesive peptides Arginine-Aspartic Acid-Glycine-Serine (RDGS) and Lysine-Serine-Serine-Arginine (KSSR). After four hours under standard cell culture conditions but in the absence of serum, adhesion of either osteoblasts or fibroblasts on surfaces patterned with the non-adhesive peptides RDGS and KSSR was random and low. In contrast, both osteoblasts and fibroblasts adhered and formed clusters onto circles modified with the adhesive peptide RGDS, whereas only osteoblasts adhered and formed clusters onto the circles modified with KRSR, a peptide that selectively promotes adhesion of osteoblasts. These results provide evidence that patterning of select peptides can direct adhesion of specific cell lines exclusively to predetermined regions on material surfaces.     

Formation of focal contacts by osteoblasts cultured on orthopedic biomaterials.

The nature of the contact sites formed during the adhesion of osteoblasts to orthopedic implant materials was investigated by fluorescence microscopy. More specifically, the cytoskeletal organization of and the focal contact formation by neonatal rat calvarial osteoblasts attaching to and spreading on 316L stainless steel, Ti-6Al-4V, Co-Cr-Mo, Synamel (hydroxyapatite), alumina, and borosilicate glass were examined. Focal contacts are regions where the plasma membrane approaches the substrate to within 10-15 nm and where bundles of cytoskeletal microfilaments terminate. Fluorescent-labeling of F-actin-containing microfilaments demonstrated a typical sequence of events as rounded, suspended osteoblasts spread onto the substrates. Immunofluorescent-labeling of the protein vinculin, which is found at the cytoplasmic face of focal contacts, initially showed the formation of streak-like focal patches. On the biomaterials, the vinculin staining subsequently extended up and along, but ventral to, the microfilament bundles. The fibrillar patterns observed at later times may evidence the formation of extracellular matrix contacts.     

Diffuse optical tomography with a priori anatomical information

Diffuse optical tomography (DOT) poses a typical ill-posed inverse problem with a limited number of measurements and inherently low spatial resolution. In this paper, we propose a hierarchical Bayesian approach to improve spatial resolution and quantitative accuracy by using a priori information provided by a secondary high resolution anatomical imaging modality, such as magnetic resonance (MR) or x-ray. In such a dual imaging approach, while the correlation between optical and anatomical images may be high, it is not perfect. For example, a tumour may be present in the optical image, but may not be discernable in the anatomical image. The proposed hierarchical Bayesian approach allows incorporation of partial a priori knowledge about the noise and unknown optical image models, thereby capturing the function-anatomy correlation effectively. We present a computationally efficient iterative algorithm to simultaneously estimate the optical image and the unknown a priori model parameters. Extensive numerical simulations demonstrate that the proposed method avoids undesirable bias towards anatomical prior information and leads to significantly improved spatial resolution and quantitative accuracy.     

Trabecular Shear Stresses Predict <Emphasis Type="Italic">In Vivo</Emphasis> Linear Microcrack Density but not Diffuse Damage in Human Vertebral Cancellous Bone

Linear microcracks and diffuse damage (staining over a broad region) are two types of microscopic damage known to occur in vivo in human vertebral trabecular bone. These damage types might be associated with vertebral failure. Using microcomputed tomography and finite element analysis for specimens of cancellous bone, we estimated the stresses in the trabeculae of human vertebral tissue for inferosuperior loading. Microdamage was quantified histologically. The density of in vivo linear microcracks was, but the diffuse damage area was not, related to the estimates of von Mises stress distribution in the tissue. In vivo linear microcrack density increased with increasing coefficient of variation of the trabecular von Mises stress and with increasing average trabecular von Mises stress generated per superoinferior apparent axial stress. Nonlinear increase in linear crack density, similar to the increase of the coefficient of variation of trabecular shear stresses, with decreasing bone stiffness and bone volume fraction suggests that damage may accumulate rather rapidly in diseases associated with low bone density due to the dramatic increase of shear stresses in the tissue. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Xx, 8759Ls, 8759Fm, 8710+e     

Specific absorbed fractions from the image-based VIP-Man body model and EGS4-VLSI Monte Carlo code: internal electron emitters

VIP-Man is a whole-body anatomical model newly developed at Rensselaer from the high-resolution colour images of the National Library of Medicine's Visible Human Project. This paper summarizes the use of VIP-Man and the Monte Carlo method to calculate specific absorbed fractions from internal electron emitters. A specially designed EGS4 user code, named EGS4-VLSI, was developed to use the extremely large number of image data contained in the VIP-Man. Monoenergetic and isotropic electron emitters with energies from 100 keV to 4 MeV are considered to be uniformly distributed in 26 organs. This paper presents, for the first time, results of internal electron exposures based on a realistic whole-body tomographic model. Because VIP-Man has many organs and tissues that were previously not well defined (or not available) in other models, the efforts at Rensselaer and elsewhere bring an unprecedented opportunity to significantly improve the internal dosimetry.     

A non-destructive method to determine the depth of radionuclides in materials in-situ.

A non-destructive method based on in-situ gamma spectroscopy is developed to determine the depth of radiological contamination in media. An innovative algorithm, Gamma Penetration Depth Unfolding Algorithm (GPDUA), uses point kernel techniques to predict the depth of contamination based on the results of the uncollided peak information from the in-situ gamma spectroscopy. The GPDUA is designed and verified through extensive Monte Carlo simulations and validated through laboratory experiments. This innovative tool promises to be "better, faster, safer, and cheaper" than the current practice in decontamination and decommissioning. The method requires the a priori knowledge of the contaminant source distribution. The applicable radiological contaminants of interest are any isotopes that emit two or more gamma rays per disintegration or isotopes that emit a single gamma ray but have gamma-emitting progeny in secular equilibrium with its parent (e.g., 60Co, 235U, and 137Cs to name a few). The predicted depths from the GPDUA algorithm using Monte Carlo N-Particle Transport Code simulations and laboratory experiments using 60Co have consistently produced predicted depths within 20% of the actual or known depth.