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AbstractThe time and phase-space dependent backward master equation is used to develop and numerically solve a coupled system of transport equations for the probability distribution of the neutron number in subregions of a spherically symmetric, reflected, subcritical plutonium sphere. The number distributions are computed for a single initial neutron injected into the assembly and localized in phase space as well as in the presence of a uniformly distributed spontaneous fission source in the fissile region. A standard multigroup, discrete ordinates scheme with second-order spatial and fully implicit time discretization proved sufficiently accurate for this application. The results presented show complex behaviors arising from the material interface and spectral effects due to neutron slowing down that cannot be encapsulated in a lumped model. Additionally, low-order spatial moments were computed both by averaging the number distributions of finite order and directly solving the transport equations for the moments using the same numerical scheme. While generally excellent agreement is observed between the two approaches, the truncation order has a noticeable effect on the accuracy of the higher moments that are computed using the number distributions.

Nowadays, the delivery of drugs by means of intravenously administered nanosized drug carriers - polymerdrug conjugates, liposomes and micelles, is technically possible. These delivery systems are mainly designed for tumour therapy, and accumulate passively into tumours by means of the well known EPR effect. Targeted nanocarriers, that additionally contain ligands for receptors expressed on cell surfaces, are also widely studied but products of this kind are not marketed, and only a few are in clinical trial. Polymeric nanoparticles (Np) able to deliver drugs to the CNS were pioneered in 1995; a number of papers have been published dealing with brain-targeted drug delivery using polymeric Np able to cross the BBB, mainly for the treatment of brain tumours. At present, however, the translation potential of these Np seems to have been exceeded by targeted liposomes, a platform based on a proven technology. This drug delivery system entered clinical trials soon after its discovery, while the challenges in formulation, characterization and manufacturing of brain-targeted polymeric Np and the cost/benefit ratio could be the factors that have prevented their development. A key issue is that it is virtually impossible to define the in vivo fate of polymers, especially in the brain, which is a regulatory requirement; perhaps this is why no progress has been made. The most advanced Np for brain tumours treatment will be compared here with the published data available for those in clinical trial for tumours outside the CNS, to highlight the knowledge gaps that still penalise these delivery systems. At present, new approaches for brain tumours are emerging, such as lipid Np or the use of monoclonal antibody (mAb)-drug conjugates, which avoid polymers. The success or failure in the approval of the polymeric Np currently in clinical trials will certainly affect the field. At present, the chances of their approval appear to be very low.

AbstractPreviously, a point kinetics model of the Medical Isotope Production Reactor has been presented, which included representations of instantaneous power, delayed neutron precursors, fuel solution temperature, radiolytic gas content, and coolant temperature. This model has been extended to include the effects of a vertically discretized temperature profile with a mixing of heat energy by eddies, boiling, and condensation and an extended model of bubble velocity and radius. It is found that the most striking change to the behavior of the system is caused by the effects of steam, which provides a strong negative feedback that tends to depress average powers in cases where the fuel solution temperature rises above the saturation temperature but can also lead to large, sharp power peaks through steam exiting the system (which can remove a large amount of negative reactivity in a short amount of time). The overall effect, however, does not lead to any unbounded power excursions. Possibilities for further extension of the model include the modeling of the composition of the plenum gas and the modeling of global pressure and its effects.

As many as 25% to 40% of unicompartmental knee replacement (UKR) revisions are performed for pain, a possible cause of which is proximal tibial strain. The aim of this study was to examine the effect of UKR implant design and material on cortical and cancellous proximal tibial strain in a synthetic bone model. Composite Sawbone tibiae were implanted with cemented UKR components of different designs, either all-polyethylene or metal-backed. The tibiae were subsequently loaded in 500 N increments to 2500 N, unloading between increments. Cortical surface strain was measured using a digital image correlation technique. Cancellous damage was measured using acoustic emission, an engineering technique that detects sonic waves (‘hits’) produced when damage occurs in material.Anteromedial cortical surface strain showed significant differences between implants at 1500 N and 2500 N in the proximal 10 mm only (p < 0.001), with relative strain shielding in metal-backed implants. Acoustic emission showed significant differences in cancellous bone damage between implants at all loads (p = 0.001). All-polyethylene implants displayed 16.6 times the total number of cumulative acoustic emission hits as controls. All-polyethylene implants also displayed more hits than controls at all loads (p < 0.001), more than metal-backed implants at loads ≥ 1500 N (p < 0.001), and greater acoustic emission activity on unloading than controls (p = 0.01), reflecting a lack of implant stiffness. All-polyethylene implants were associated with a significant increase in damage at the microscopic level compared with metal-backed implants, even at low loads. All-polyethylene implants should be used with caution in patients who are likely to impose large loads across their knee joint. Cite this article: Bone Joint J2013;95-B:1339–47.

Structural health monitoring (SHM) is of paramount importance in the aircraft industry: not only to ensure the safety and reliability of aircraft in flight and to ensure timely maintenance of critical components, but also increasingly to monitor structures under test for airworthiness certification of new designs. This article highlights some of the recent advances in the acoustic emission (AE) technique as applied to SHM, and the new approaches that are crucial for the successful use of AE data for diagnostic purposes. These include modal analysis, enhanced location techniques, and novel signal processing approaches. A case study is presented on a landing gear component undergoing fatigue loading in which a linear location analysis using conventional techniques identified the position of fracture and final rupture of the specimen. A principal component analysis approach was used to separate noise signals from signals arising from fatigue cracks, which identified and located further fatigue crack positions, subsequently confirmed by magnetic particle inspection. Kernel probability density functions are used to aid visualization of the damage location.

AbstractThis paper presents two new methods for discretizing the angular dimension of the Boltzmann transport equation that describes the transport of neutral particles such as neutrons and photons. Our methods represent the direction of particle travel using linear and quadratic varying approximations over a quadrilateral partitioning of the unit sphere’s surface (which is used to represent a particle’s direction), which is similar to the approximations provided by a finite element expansion. However, our approximations are generated using a second generation spherical wavelet technique. This method generates hierarchical sets of compactly supported basis functions that are important properties for our future work in applying adaptive resolution in the transport equation’s angular dimension. These new wavelet methods are applied to five monoenergetic transport problems to demonstrate their capabilities to efficiently represent the angular flux. Particular emphasis is placed on their ability to approximate particle transport in problems involving extreme material cross sections, namely, particle streaming through voids and their transport through highly scattering media. We are able to show that the methods work well against the common methods SNand PNwhen used within established radiation transport codes.

AbstractA new method for applying anisotropic resolution in the angular domain of the Boltzmann transport equation is presented. The method builds on our previous work in which two spherical wavelet bases were developed for representing the direction of neutral particle travel. The method proposed here enables these wavelet bases to vary their angular approximations so that fine resolution may be applied only to the areas of the unit sphere (representing the direction of particle travel) that are important. We develop an error measure that operates in conjunction with the wavelet bases to determine this importance. A procedure by which the angular resolution is gradually refined for steady-state problems is also given.The adaptive wavelets are applied to three test problems that demonstrate the ability of the wavelets to resolve complex fluxes with relatively few functions, and to achieve this a particular emphasis is placed on their ability to approximate particle streaming through ducts with voids. It is shown that the wavelets are capable of applying the appropriate resolution (as dictated by the error measure) to the directional component of the angular flux at all spatial positions. This method therefore offers a new and highly efficient adaptive angular approximation method.

This work describes the setup and operation of an X-ray diffraction (XRD) cell for hydrate studies at elevated pressures (hereon we call it ‘‘high-pressure cell’’ for convenience). Most hydrate XRD measurements have been performed at low temperatures to ensure hydrate stability at atmospheric pressure. As a result, extrapolation has been required to determine hydrate volume at in situ conditions. With high pressure capabilities, however, this system can extend current structural knowledge without extrapolation, leading to less error in predictive modeling and a more accurate view of in situ hydrates. The cell has both low- and high-temperature capabilities, operating from 77 to 300 K using liquid nitrogen boil-off as a means of refrigeration, and can maintain pressures from 14 kPa to 7 MPa. Preliminary measurements of carbon dioxide hydrates at in situ conditions have been obtained and lattice parameters are comparable to those in the literature.

Objectives:: To describe the development of a research program focused on cancer-related fatigue in children and adolescents and the resulting definition and model. Data Sources:: Research studies, review articles, and clinical examples. Conclusions:: Fatigue has been identified by children and adolescents who are receiving treatment for cancer as one of the most distressing treatment-related symptoms they experience, yet fatigue is rarely assessed by health professionals and infrequently reported by patients or their parents. Implications for Nursing Practice:: An improved understanding of the contributory and alleviating factors that cause fatigue in this patient population will provide them with greater comfort during treatment for cancer.

Cultures of embryonic day 17 (E17) rat adrenal and neonatal bovine adrenal cells were conditionally immortalized with the temperature-sensitive allele of SV40 large T antigen (tsTag) and chromaffin cell lines established. Indicative of the adrenal chromaffin phenotype, these cells expressed immunoreactivity (ir) for tyrosine hydroxylase (TH), the first enzyme in the synthetic pathway for catecholamines. At permissive temperature in vitro (33°C), these chromaffin cells are proliferative, have a typical rounded chromaffin-like morphology, and contain detectable TH-ir. At nonpermissive temperature in vitro (39°C), these cells stop proliferating and express increased TH-ir. When these immortalized chromaffin cells were transplanted in the lumbar subarachnoid space of the spinal cord 1 week after a unilateral chronic constriction injury (CCI) of the rat sciatic nerve, they survived longer than 7 weeks on the pia mater around the spinal cord and continued to express TH-ir. Conversely, grafted chromaffin cells lost Tag-ir after transplant and Tag-ir was undetectible in the grafts after 7 weeks in the subarachnoid space. At no time did the grafts form tumors after transplant into the host animals. These grafted chromaffin cells also expressed immunoreactivities for the other catecholamine-synthesizing enzymes 7 weeks after grafting, including: dopamine-β-hydroxylase (DβH) and phenylethanolamine-N-methyltransferase (PNMT). The grafted cells also expressed detectable immunoreactivities for the opioid met-enkephalin (ENK), the peptide galanin (GAL), and the neurotransmitters γ-aminobutyric acid (GABA) and serotonin (5-HT). Furthermore, after transplantation, tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI were significantly reduced during a 2–8-week period, related to the chromaffin cell transplants. The maximal antinociceptive effect occurred 1–3 weeks after grafting. Control adrenal fibroblasts, similarly immortalized and similarly transplanted after CCI, did not express any of the chromaffin antigenic markers, and fibroblast grafts had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that embryonic and neonatal chromaffin cells can be conditionally immortalized and will continue to express the phenotype of primary chromaffin cells in vitro and in vivo; grafted cells will ameliorate neuropathic pain after nerve injury and can be used as a homogeneous source to examine the mechanisms by which chromaffin transplants reverse chronic pain. The use of such chromaffin cell lines that are able to deliver antinociceptive molecules in models of chronic pain after nerve and spinal cord injury (SCI) offers a novel approach to pain management.

Novel polyamine carbamates have been designed and prepared from cholesterol. Our synthesis uses an orthogonal protection strategy based upon trifluoroacetyl and Boc-protecting groups. These unsymmetrical polyamine carbamates have been prepared from symmetrical (e.g., spermine and thermine) polyamines. Detailed interpretations of ¹H and ¹³C NMR spectroscopic data led to the unambiguous assignment of these polyamine carbamates. These target conjugates contain a variety of positive charges distributed along methylene chains. Their pKas have been determined potentiometrically for conjugates substituted with up to five amino functional groups. Condensation of calf thymus DNA into particles was monitored using light scattering at 320 nm. Salt-dependent binding affinity for calf thymus DNA was determined using an ethidium bromide fluorescence quenching assay. These cholesteryl polyamine carbamates are models for lipoplex formation with respect to gene delivery (lipofection), a key first step in gene therapy.

The use of cell lines utilized as biologic “minipumps” to provide antinociceptive molecules, such as GABA, in animal models of pain is a newly developing area in transplantation biology. The neuronal cell line, RN33B, derived from E13 brain stem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat GAD67cDNA (glutamate decarboxylase, the synthetic enzyme for GABA), and the GABAergic cell line, 33G10.17, was isolated. The 33G10.17 cells transfected with the GAD67gene expressed GAD67protein and synthesized low levels of GABA at permissive temperature (33°C), when the cells were proliferating, and increased GAD67and GABA during differentiation at nonpermissive temperature (39°C) in vitro, because GAD67protein expression was upregulated with differentiation. A control cell line, 33V1, transfected with the vector alone, contained no GAD67or GABA at either temperature. These cell lines were used as grafts in a model of chronic neuropathic pain induced by unilateral chronic constriction injury (CCI) of the sciatic nerve. Pain-related behaviors, including cold and tactile allodynia and thermal and tactile hyperalgesia, were evaluated after CCI in the affected hind paw. When 33G10.17 and 33V1 cells were transplanted in the lumbar subarachnoid space of the spinal cord 1 week after CCI, they survived greater than 7 weeks on the pia mater around the spinal cord. Furthermore, the tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI was significantly reduced during the 2–7-week period after grafts of 33G10.17 cells. The maximal effect on chronic pain behaviors with the GABAergic grafts occurred 2–3 weeks after transplantation. Transplants of 33V1 control cells had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that a chronically applied, low local dose of GABA presumably supplied by transplanted cells near the spinal dorsal horn was able to reverse the development of chronic neuropathic pain following CCI. The use of neural cell lines that are able to deliver inhibitory neurotransmitters, such as GABA, in a model of chronic pain offers a novel approach to pain management.

The purpose of this research study was to define fatigue experienced by children with cancer and to begin development of a conceptual model.Two major Paediatric Cancer Centers in the Southern USA participated in this study. Children who participated in this study were in the out-patient clinic or in the hospital. Five focus groups with a total of 14 children between 7 and 12 years-of-age were held over a 2-month period of time. Focus groups were used to first assess the contextual understanding and essential attributes of fatigue in 7 to 12-year-old children. Each focus group session lasted 30 to 45 minutes, was audiotaped and transcribed verbatim.A team of four researchers used content analysis to evaluate the transcripts. Codes and definitions were developed for the characteristics of fatigue, causes of fatigue and what alleviates fatigue. Concept analysis was completed as a basis for developing the conceptual framework. Eight codes emerged to define fatigue. Seven codes were used to describe the causes of fatigue.An additional three codes were used to describe what alleviated fatigue.A conceptual definition for fatigue experienced by children with cancer emerged from the data, and a conceptual model was developed to demonstrate relationships between fatigue and contributory and alleviating factors.The conceptual work for model development contributes to understanding fatigue in children with cancer and serves as a basis for establishing operational definitions

Despite improved event-free survival of older children with acute lymphocytic leukemia (ALL), infants <1 year of age continue to have a very poor prognosis. A new therapy designed specifically for infants with ALL was initiated.

PURPOSE: Possible mechanisms of movement of malignant cells within the peritoneal cavity during CO2 insufflation and laparoscopy involve direct transfervia laparoscopic instruments or dispersion of cells by CO2 or water vapor. Anin vivo model has been developed to study these mechanisms. METHODS: Laparoscopy was performed on an animal model (domestic white pig). Cells derived from colorectal cancer cell line Lim 1215 were injected to lie free within the peritoneal cavity. A polycarbonate filter system with a 5-micron pore diameter was used to examine CO2 expelled from the peritoneal cavity, during laparoscopy and manipulation of abdominal viscera, for malignant cells. Laparoscopic instruments and laparoscopic ports were washed independently, and fluid was centrifuged and examined for malignantcells. RESULTS: Malignant cells were identified on 1 of 30 filters used to examine exhaust carbon dioxide. Malignant cells also were identified from 2 of 10 washings from laparoscopic ports and from 4 of 10 washings of laparoscopic instruments. CONCLUSIONS: These results suggest that movement of cells throughout the peritoneal cavity during laparoscopy isvia contaminated instruments, but local cell movement by dispersion possibly within water vapor from the port may also occur.

Little information concerning the genome of either Campylobacter jejuni or Campylobacter coli is available. Therefore, we constructed genomic maps of C. jejuni UA580 and C. coli UA417 by using pulsed-field gel electrophoresis. The genome sizes of C. jejuni and C. coli strains are approximately 1.7 Mb, as determined by SalI and SmaI digestion (N. Chang and D. E. Taylor, J. Bacteriol. 172:5211-5217, 1990). The genomes of both species are represented by single circular DNA molecules, and maps were constructed by partial restriction digestion and hybridization of DNA fragments extracted from low-melting-point agarose gels. Homologous DNA probes, encoding the flaAB and 16S rRNA genes, as well as heterologous DNA probes from Escherichia coli, Bacillus subtilis, and Haemophilus influenzae, were used to identify the locations of particular genes. C. jejuni and C. coli contain three copies of the 16S and 23S rRNA genes. However, they are not located together within an operon but show a distinct split in at least two of their three copies. The positions of various housekeeping genes in both C. jejuni UA580 and C. coli UA417 have been determined, and there appears to be some conservation of gene arrangement between the two species.

Persistent absence from school is often associated with anxiety and with difficulty in relating to other people. These and other factors were examined to determine their contribution to the identification of persistent absenteeism in the upper junior and lower secondary age groups. Questionnaires were administered to 190 children, including persistent absentees, to measure: (a) their relationship with parents, teachers and peers and (b) their anxiety level. Other information was obtained from teachers and pupil records. A multiple regression analysis was used to determine the predictive efficiency of the variables at both age levels. The strength of peer and teacher relationships, together with ability, suggested that thecauses of persistent absenteeism were likely to be school related. The uncertainty about the causal importance of the home was underlined by the weakness of the home related factors. Anxiety seemed to be of value in differentiating between truants and other persistent absentees.

A DNA duplex coding for the 53 amino acids of human beta-urogastrone has been synthesised. Computer assisted design of the gene included restriction endonuclease sites for plasmid insertion, a termination codon and two triplets coding for lysine at the 5'-end of the structural gene. The synthesis involved preparation of 23 oligodeoxyribonucleotides by phosphotriester procedures coupled to rapid HPLC techniques. The gene was constructed in two halves by enzymatic ligation of the oligonucleotides and cloned into a specially constructed chimeric plasmid vector. Escherichia coli K12 MRC8 was transformed by the plasmid and clones containing the full gene sequence were isolated and characterised.

C3H/Bi mice developed autoantibodies after repeated inoculations of isolated membranes from primary tissue cultures of a syngeneic ascites lymphoma in which Newcastle disease virus had grown. This was in addition to the tumor transplantation resistance and cytotoxic antibodies previously demonstrated. The complement-fixing antibodies were completely removed from sera by adsorption with ascites tumor cells but only partially by normal mouse liver powder or C3H/Bi erythrocytes. With continued immunization, antibodies to deoxynucleoprotein and heterophile reagins also appeared. After several months, mice showing these serological reactions died with a wasting disease characterized by loss of lymphoid tissue and scarred, atrophied kidneys. No significant antibody response or autoimmune disease occurred in mice receiving membranes from uninfected syngeneic ascites lymphoma.

Adsorption of paramyxoviruses to separated membranes of tumor cells produces neoantigens that are immunogenic in syngeneic mice (xenogenization). Thus it became possible to study this process by using modified virus or virus fractions. Membranes with adsorbed viral derivatives produced an immune response which was measured by cytotoxic and complement fixing antibodies and the appearance of autoimmune disease. The effect of viral preparations with reduced F (fusion) protein activity was compared to treatment of membranes with equivalent amounts of active or inactive virus as measured by hemagglutination. Viral preparations without hemolytic activity showed diminished adsorption to membranes and the immune response was reduced. Triton X100 and desoxycholate extracted from membranes immunogenic material with associated paramyxovirus antigens.

Genomic DNA from 30 strains of Helicobacter pylori was subjected to pulsed-field gel electrophoresis (PFGE) after digestion with NotI and NruI. The genome sizes of the strains ranged from 1.6 to 1.73 Mb, with an average size of 1.67 Mb. By using NotI and NruI, a circular map of H. pylori UA802 (1.7 Mb) which contained three copies of 16S and 23S rRNA genes was constructed. An unusual feature of the H. pylori genome was the separate location of at least two copies of 16S and 23S rRNA genes. Almost all strains had different PFGE patterns after NotI and NruI digestion, suggesting that the H. pylori genome possesses a considerable degree of genetic variability. However, three strains from different sites (the fundus, antrum, and body of the stomach) within the same patient gave identical PFGE patterns. The genomic pattern of individual isolates remained constant during multiple subcultures in vitro. The reason for the genetic diversity observed among H. pylori strains remains to be explained.

Two glutamate-binding proteins (71 and 63 kDa) were previously purified from synaptic plasma membranes (Chen, J.-W., Cunningham, M.D., Galton, V., and Michaelis, E. K. (1988) J. Biol. Chem. 263, 417-426). These proteins may play a role in glutamate neurotransmission in brain. Polyclonal antibodies were raised against the denatured glutamate-binding proteins in rabbits, including sets of antibodies against each of the binding proteins. The antibodies reacted specifically against both 71- and 63-kDa proteins. The antibodies recognized the denatured form of the proteins in Western blots and the native state of the proteins in enzyme-linked immunosorbent assays and in immunoaffinity chromatography and extraction procedures. All antibodies labeled most strongly the 71-kDa protein in Western blots, but extracted both proteins from solubilized synaptic membrane preparations. These findings indicate that the two proteins are closely related immunologically but the reactivity on Western blots differs between these two proteins. Immunoextraction of the 71- and 63-kDa proteins led to a approximately 60% decrease in L-[3H]glutamate-binding activity associated with synaptic membrane proteins. Of the brain subcellular fractions examined, the isolated synaptic plasma membranes had the strongest reaction in enzyme-linked immunosorbent assays toward the antiglutamate-binding protein antisera. Electron microscopy combined with gold particle immunohistochemistry revealed the sites labeled by the antibodies as entities present either on the surface or within the postsynaptic membranes and the associated densities of brain nerve ending particles (synaptosomes). Immunohistochemical procedures of gold labeling with silver enhancement of labeled sites revealed selective neuronal labeling in brain regions enriched in glutamate neurotransmitter pathways such as the hippocampus. Labeling was along dendrites and around cell bodies of pyramidal neurons. Based on the pattern of histochemical labeling, the distribution of immune reactivity in synaptic membranes, and the extractions of a major component of membrane glutamate-recognizing proteins by the antibodies, the glutamate-binding proteins must play a role in glutamate neurotransmission.

Dopamine D2-like receptors play an important role in the pharmacotherapy of psychotic disorders. Molecular and cellular techniques have identified distinct gene products (D2-long, D2-short, D3 and D4) displaying the D2 receptor pharmacology. However, the contribution of each subtype in antipsychotic effects of or their physiological role remain unclear. Here we describe the pharmacological effects of a selective D4 antagonist, U-101387. U-101387 displayed moderately high affinity (Ki = 10 nM) and selectivity for the dopamine D4.2 receptor expressed in clonal cell lines. It lacked measurable affinity for not only other dopamine receptors but also noradrenalin, serotonin and histamine receptor families (Ki > 2000 nM). It fully and dose-dependently antagonized quinpirole-induced cAMP inhibition (without producing any effect by itself) in stably transfected cells. U-101387 also displayed excellent oral bioavailability, brain penetration and other pharmacokinetic characteristics. Unlike classical neuroleptics (e.g., haloperidol), U-101387 neither blocked acute behavioral effects of amphetamine or apomorphine nor did it alter spontaneous locomotion by itself. Additionally, U-101387 was without effect in behavioral and biochemical tests predictive of extrapyramidal and neuroendocrine side effects. Consistent with the lack of autoreceptor function of D4, acute administration of U-101387 failed to alter dopamine neuronal firing by itself or reverse the inhibition produced by dopamine agonists and to affect monoamine turnover in areas innervated by the mesencephalic or hypothalamic dopamine neurons. However, U-101387 potently induced c-fos mRNA expression in the infralimbic/ventral prelimbic cortex to a level similar to that produced by the atypical antipsychotic, clozapine. This is consistent with the predominantly cortical distribution of the D4 receptor. Taken together, these results demonstrate that the D4-selective antagonist, U-101387, produces effects that are distinct from those of the nonselective D2 antagonists as well as D3-preferring agents. U-101387 offers a unique tool to understand the role of dopamine D4 receptors in diseases involving central dopamine systems.

Recently developed techniques for isolating forespores from bacilli at all stages of spore morphogenesis have been exploited to investigate the contribution of each of the two compartments of the sporulating cell to the overall pattern of protein synthesis and degradation during sporulation in Bacillus megaterium. These studies have shown: (1) that protein synthesis continues in both compartments throughout spore morphogenesis; (2) that the degradation of proteins made at all times during vegetative growth and sporulation is confined to the mother-cell compartment; (3) that proteins synthesized in the mother-cell compartment during sporulation are subsequently degraded more rapidly than proteins synthesized during vegetative growth. This rate of degradation increases the later the proteins are synthesized in the sporulation sequence. Mature spores were disrupted, and the percentage of the total protein in soluble and particulate fractions was determined. Pulse-labelling experiments were performed to investigate the extent to which the proteins of these two fractions are newly synthesized during sporulation. These data were used to calculate the extent of capture of vegetative cell protein at the time of formation of the forespore septum. The value obtained is consistent with evidence from electron micrographs and supports a model for the origin of spore protein in which there is no protein turnover in the developing forespore.

The purpose of the present study was to characterize dopaminergic D2 receptor-mediated regulation of catecholaminergic neurons in the diencephalon by examining the acute effects of the potent and selective D2 agonist quinelorane (LY163502; trans-(-)-5,5a,6,7,8,9,9a,10-octahydro-6-propylpyrimido [4,5-g] quinolin-2-amine dihydrochloride dihydrate) on concentrations of 3,4-dihydroxyphenylacetic acid, dopamine, 3-methoxy-4-hydroxyphenylethyleneglycol and norepinephrine in the dorsomedial nucleus of the hypothalamus and horizontal limb of the diagonal band of Broca of intact and norepinephrine-depleted male rats. For comparative purposes, various other diencephalic brain regions and the nucleus accumbens were also examined. The results of this study reveal that quinelorane decreases the activity of dopaminergic neurons in the nucleus accumbens, horizontal limb of the diagonal band of Broca and dorsomedial nucleus of the hypothalamus, whereas it increases the activity of noradrenergic neurons projecting to the dorsomedial nucleus of the hypothalamus, but not the horizontal limb of the diagonal band of Broca. These inhibitory and stimulatory actions of quinelorane are blocked by or reverse the effects of the D2-selective antagonist raclopride, indicating that quinelorane is acting at D2 receptors. Taken together, these results indicate that quinelorane inhibits DA neurons within the diencephalon, whereas it activates a subpopulation of noradrenergic neurons projecting to this brain region.

Newcastle disease virus was adsorbed to a membrane fraction prepared from splenocytes, and the resulting preparation was injected into syngeneic C3H mice. Complement fixing and cytotoxic antibodies reactive with syngeneic tissue and intact cells developed, and some mice died with autoimmune disease characterized by wasting, severe kidney damage, and loss of lymphoid tissue as described previously for animals receiving the membrane fraction of a syngeneic lymphoma in which Newcastle disease virus had grown. Similar experiments were done with L929 mouse fibroblasts and allogeneic spleen membrane fractions. With syngeneic spleen tissue and L929 fibroblasts, serological evidence of autoimmunity appeared after several injections, but deaths from autoimmunity were considerably delayed unless Freund's complete adjuvant was given with the antigen. The results suggest that antigen modification occurs after adsorption of the paramyxovirus to normal tissue as well as lymphoma cell membranes.

Although there is an extensive literature on the therapeutic effects of flavonoid substances, erroneously referred to as vitamin P, such as citrin,® rutin, hesperidin and related compounds and crude extracts (e. g., of citrus peels and rose hips), little has been published on their absorption, metabolism and excretion. This becomes important in connection with claims of the vitamin-like nature of the substances, and the widespread use of proprietary preparations containing rutin and related compounds for pathologic conditions involving capillary fragility and hemorrhage, hypertension and radiation disease.Many of the flavonoids are common plant pigments, along with the related anthocyanins of grapes, berries, beets, citrus and other fruits, vegetables and flowers.It has been demonstrated that anthocyanin pigments such as cyanidin and delphinidin are not appreciably absorbed on oral ingestion by most higher animals, and when injected parenterally in animals they are not metabolized, being renally excreted unchanged.1 Similar observations

In 1916, Addis1 introduced the determination of the ratio under certain standard conditions as a measure ofthe amount of functioning renal tissue. The adequacy of this ratio as measured under the standard conditions for this purpose was demonstrated in a number of ways. It is a reasonable measure of renal function;2 the variation in "experimental nephritis" was found3 to agree well with the structural changes in the kidneys, and the compensatory renal hypertrophy as measured by the ratio coincided with the anatomic measurements.4 Lastly, it was shown5 that in rabbits there existed a linear relationship between the magnitude of the ratio and the weight of the kidneys, an observation since confirmed for the rat6 and the dog.7 Taylor, Drury and Addis5 found that in rabbits the kidney weight varied directly in proportion to the body surface and bore a more constant relation to this figure than to any

The addition of a large quantity of ground psyllium seed to the diet of albino rats or dogs is followed by a darkening of the kidneys when examined grosdy. If the feeding is continued for a longer period brown pigment granules become evident microscopically in the renal tubules. Whole psyllium seed produces no renal pigmentation.

Epinephrine protects adrenal insufficient rats from the edema and mortality caused by the intraperitoneal administration of egg white. Mortality is prevented by doses (0.04 mg/kg) which are not able to prevent edema in rats with intact adrenals.The antihistaminic Phenergan, N-dimethyl-amino-2-propyl-l-thiodiphenylamine (“3277 RP”), in doses as low as 5 mg/kg prevent death from egg white edema in adrenalectomized rats.“SY-28”, N-(2-bromoethyl)-1-naphthalene-methylamine hydrobromide, a Dibenamine congener possessing both antihistaminic and adrenergic blocking activity, also prevents the edema and death, but is in itself toxic to adrenalectomized rats.“SKF-501”, N-(9-fluorenyl)-N-ethyl-β-chloroethylamine, a Dibenamine cogener with potent adrenergic blocking powers but with a low toxicity and without antihistamine action, also inhibits the edema and decreases the mortality.The possible modes of action are discussed.

Koenig and Koenig1have described an acute pulmonary edema following the administration of ammonium salts to different species. It appears to be specifically a result of the ammonium ion. The occurrence and gross appearance of this edema resembles epinephrine induced pulmonary edema and in an effort to obtain information about the mechanism of the ammonium pathology a study has been made of its relation to edema due to epinephrine and adrenergic stimuli.Experimental.Epinephrine induced pulmonary edema may be prevented by adrenergic blocking agents.2, 3Their influence was observed upon ammonium pulmonary edema. Unfasted guinea pigs were divided into groups with the same sex distribution. All groups were lightly etherized to pass a stomach tube. Group 1, the controls, were given a sham dose of 10 cc water per kg body weight. All other groups received 1200 mg/kg of a 12% solution of NH4CI by oral gavage. Ten minutes before receiving the ammonium salt groups 3, 4 and 5 respectively received by intravenous injection in 1 cc saline/kg; 2 mg/kg of a B-haloethylamine, N-(9-fluorenyl) -N-ethyl-B-chloroethylamine-HCl (“SKF-501”); 2.5 mg/kg N-(2-chloroethyl)-N-ethylbenzhydrylamine-HCl (“SY-2”), which like “SKF-501” is an effective adrenergic blocking agent; and 1.5 mg/kg of the potent anttihistaminic N-B-dimethylaminopropylthiodiphenylamine - HCI (“Phenergao”, 3277 R.P.). The presence of pulmonary edema was determined at an autopsy by gross inspection and lung weight was used as a measure of its extent.The summarized data comprise Table I. Group 1 was killed with ether while all of the animals in the other groups succumbed with convulsions 5-30 minutes after receiving the ammonium salt. The two adrenergic blocking agents and the antihistaminic all were without influence upon mortality. Since both of the adrenergic blocking agents completely prevented the ammonium edema but not the mortality, we may conclude that pulmonary edema need not be the cause of death fromtoxic doses of ammonium salts. The anthistaminic was without effect on the ammonium edema, which in this respect resembles the fulminating pulmonary edema due to epinephrine.2