bluuebunny/crossref_metadata_2025 huggingface dataset:
AFFINITY CHROMATOGRAPHY IN THE SEPARATION OF HUMAN ALPHA1‐ANTITRYPSIN (α1‐AT) AND ANTITHROMBIN‐III (AT‐III)
Authors: D'Souza S , Ananthakrishnan R
Published: November 2007

The two antiproteases α1‐antitrypsin (α1‐AT) and antithrombin‐III (AT‐III) have been purified simultaneously from human plasma. Purification procedure consisted of gel filtration on Sephadex G‐200 after initial processing of plasma, followed by ion exchange chromatography on DEAE‐Sephadex A50 and DEAE‐celllulose, at a pH of 9·0 and pH 8·3 respectively. The two proteins could not be separated by any of these procedures including a lower pH (7·4) in ion exchange chromatography. Affinity chromatography on heparin‐Sepharose separated the proteins since α1‐AT did not bind to the matrix. Alpha1‐AT unbound to the heparin‐Sepharose was subsequently purified through con A‐Sepharose affinity column. The final yield of both the proteins was about 20%. The molecular weight estimated on SDS electrophoresis for AT‐III and α1‐AT was 63,000 and 50,000, respectively.
CLEARANCE OF BACTERIA FROM LUNGS OF MICE AFTER OPSONISING WITH IgG OR IgA
Authors: Cooper J McA , Rowley D
Published: November 2007

The clearance of organisms from the lungs of mice was followed after aerosol administration. Preopsonisation of the organisms with immune serum, as a source of specific antibody, enhanced the rate of pulmonary clearance while s.IgA delayed clearance. In the peritoneal cavity, bacteria pre‐treated with immune serum were cleared more rapidly than unopsonised bacteria, but s.IgA had little effect. The presence of Fc receptors for IgG and not s.IgA on alveolar macrophages suggests that, in secretions, IgG is the predominant antibody promoting phagocytosis by alveolar macrophages and that any protective effect of s.IgA is not mediated by these cells.
A METHOD FOR THE ANALYSIS OF SIGMOID STIMULUS‐RESPONSE CURVES
Authors: Leppard P , Faris I , Jamieson GG , Ludbrook J
Published: November 2007

This paper describes a method, using an interactive computer programme, for fitting a curve to data which is expected to assume a sigmoid form. The programme is specifically designed to generate best estimates of the limits and maximum slope of stimulus‐response curves for the carotid sinus baroreceptor reflex, but is applicable to curve‐fitting tasks in other fields such as immunology, pharmacology, biochemistry and neurophysiology.
DEVELOPMENT IN VITRO OF CYTOTOXIC LYMPHOCYTES AGAINST MURINE CYTOMEGALOVIRUS
Authors: Ho Monto , Ashman Robert B
Published: November 2007

Lymphocytes cytotoxic for mouse embryo fibroblasts (MEF) infected with murine cytomegalovirus (MCMV) were produced by in vitro culture of “memory” spleen cells with UV‐irradiated, MCMV‐infected, MEF. Cytotoxic lymphocytes were developed from spleen cells of mice 10 to 240 days after infection with MCMV, The cytotoxic cells carried the theta and Ly 2 antigens, and were H‐2 restricted in the recognition of infected target cells.
ACCELERATED CLEARANCE OF UNINFECTED RED CELLS FROM PLASMODIUM BERGHEI‐INFECTED MOUSE BLOOD IN NORMAL MICE
Authors: Howard Russell J , Mitchell Graham F
Published: November 2007

51Cr‐labelled uninfected cells, separated from Plasmodium berghei‐infected mouse blood using the fluorescence‐activated cell sorter, were cleared more rapidly than normal mouse erythrocytes after intravenous injection into normal mice.
THE BILIARY EXCRETION OF SULFBROMOPHTHALEIN IN THE PIG
Authors: Rose Margaret , Ham John M
Published: November 2007

The characteristics of the hepatic metabolism of Sulfbromophthalein (BSP) have not been described previously for the pig. This is an important deficiency, since the pig is particularly suitable for studies of hepatic physiology and pharmacology which might apply to man.

The aim of these experiments was to establish the pattern of serum clearance and biliary excretion of BSP and to determine that dose which would produce a maximal concentration in bile.

A dose response and pattern of biliary excretion of BSP was studied at three dose levels administered either as a single bolus or a continuous infusion. All experiments were performed in conscious, conditioned pigs. The patterns of serum clearance and biliary excretion were found to be similar to other laboratory animals and to man. Maximal biliary concentration of BSP was achieved by a single bolus of 5.9 μmol/kg or a constant infusion of 0.59 μmol/kg/min. At these dose levels no significant alteration in bile flow was demonstrated nor was there any correlation between bile flow and BSP excretion. Supra‐maximal doses produced a significant increase in bile flow and with these doses there was a significant positive correlation between bile flow and BSP excretion.
EFFECTS OF THYMIDINE ANALOGUES ON MURINE AND HUMAN CELLS
Authors: Smellie SG , Parsons PG
Published: November 2007

Three mouse tumour cell lines grew continuously in 3 μM 5‐bromodcoxyuridine (BUdR). One line (MC‐2) produced a retrovirus and altered in morphology in the presence of BUdR or 5‐iododeoxyuridine (IUdR). These effects, which could be reversed by growth in normal medium, were similar to those reported for the B‐16 mouse melanoma line. The B‐16 line used in this study, however, as well as a variety of human cells (six melanoma lines and three fibroblast strains), were much more sensitive to BUdR, 0·03–0·1 μM being the maximum tolerated levels for continuous growth. No virus production or changes in morphology were induced in these cells by BUdR, deoxyuridine (UdR), 5‐fluorodcsoxyuridine (FUdR) or thymidine (TdR). The results of cell labelling and growth studies showed a correlation of Incorporation of BUdR into DNA with toxicity. Compared on a competitive basis with 1 μM TdR, the order of incorporation of 1 μM nucleosides by two human cell lines was TdR = BUdR = 1UdR ≥ UdR ≥ ≥ FUdR. In contrast to previous reports that FUdR is incorporated into RNA but not into DNA, half of the FUdR label was found in alkali‐stable, DNase‐sensitive material. Over 90% of the other compounds was incorporated into DNA. All of the UdR and 60% of the 1UdR label was incorporated as thymidine: this conversion could be inhibited by labelling in the presence of FUdR.
IMMUNOPRECIPITATION OF BIOSYNTHETICALLY‐LABELLED PRODUCTS IN THE IDENTIFICATION OF ANTIGENS OF MURINE RED CELLS INFECTED WITH THE PROTOZOAN PARASITE, PLASMODIUM BERGHEI
Authors: Knopf Paul M , Brown Graham V , Howard Russell J , Mitchell Graham F
Published: November 2007

In this methodological paper an immunoprecipitation technique has been optimised for the identification of antigens of Plasmodium berghei‐infected blood which react with antibody specificities in a host‐protective antiserum. Extracted 3H‐leucine biosynthetically‐labelled products of infected blood were sequentially reacted and precipitated with sera from mice which had been exposed to P. berghei but which were either non‐protected or protected against lethal infection, protection having been shown to be transferable to naive recipients with the appropriate scrum. As analysed by polyacrylamide gel electrophoresis under reducing conditions, a small number of molecular species was detected in immunoprecipitates using host‐protective sera which were apparently not quantitatively precipitated out of the complex mixture of labelled products of infected blood using sera from non‐protected mice.
FACTORS AFFECTING THE ABILITY OF VARIOUS STRAINS OF ENTEROBACTERIACEAE TO INDUCE TUMOUR RESISTANCE IN MICE
Authors: Vingelis Velta , Ashman Leonie K , Kotlarski Ieva
Published: November 2007

Primary infection of mice with Salmonella enteritidis 11RX (11RX) confers resistance to challenge with 104 LD50 doses of Ehrlich Ascites tumour (EAT). A lipopolysaccharide‐free protein extract of 11RX is capable of eliciting delayed type hypersensitivity (DTH) reactions in these mice and of “recalling” tumour resistance in long‐term 11RX immunised mice, which no longer exhibit any resistance to tumour challenge.

In the present study, we have examined the ability of five other strains of Enterobacteriaciae to induce similar effects. Primary i.p. injection of S Chester. S. luton or S. typhimurium G30 into mice resulted in persisting infections and the induction of peritoneal exudate cells (PEC) which were tumouricidal in vitro. DTH reactions could also be elicited in these animals with protein extracts of the homologous or the 11RX strain of salmonella. S. friedenan and E. coli K12, which did not persist in mice, did not elicit tumouricidal PEC and did not sensitize mice for DTH reactions. However, protein extracts from all the five strains could elicit tumouricidal PEC and DTH reactions in long‐term 11 RX‐immunised mice (but not in normal mice).

The results imply that a wide range of Enterobacteriaceae may possess antigen(s) which can be involved in tumour resistance, provided that these antigen(s) are presented in such a way that a cellular immune response develops.
ACCELERATED REJECTION OF NEMATOSPIROIDES DUBIUS INTESTINAL WORMS IN MICE SENSITIZED WITH ADULT WORMS
Authors: Hurley James C , Day Karen P , Mitchell Graham F
Published: November 2007

After oral administration of infective third stage larvae (L3) of Nematospiroides dubius to young mice, intestinal worms persist for many weeks. However, in mice injected parenterally with N. dubius adult worms, the intraluminal intestinal infection arising after L3 administration can be terminated within 3 to 4 weeks. This accelerated rejection is seen in sensitized BALB/c mice (and (CBA/H × BALB/c)F1 mice) and in particular females, but has not been demonstrated in sensitized CBA/H mice. In female BALB/c mice, small numbers of living worms are more effective at sensitization than dead worms, intraperitoneal and subcutaneous implantations are both effective, and products from adult worms incubated in vitro (i.e. ‘excretory/secretory’ (ES) products) will sensitize but only with very high doses in adjuvant. Using appropriate isolated antigen preparations, comparative immunoparasitological analyses in different mice should provide clues on the nature of host‐protective immunities against intestinal nematode infections which are potentially chronic. From the present studies, two groups which differ most dramatically in the consequences of adult worm sensitization are young male CBA/H versus older female BALB/c mice.
AN IMMUNOHISTOCHEMICAL STUDY OF SECRETAGOGUE‐INDUCED SECRETION OF EPIDERMAL GROWTH FACTOR IN THE SUBMANDIBULAR SALIVARY GLANDS OF MICE
Authors: Steidler NE , Reade PC
Published: November 2007

Routine histological and indirect immunofluorescence techniques were used to examine the histological details of changes in the distribution of epidermal growth factor (EGF) in the submandibular salivary glands of mice during secretion. Comparisons were made between glands of normal mice and those of mice given one of a number of secretagogues at various times prior to sampling. Normal submandibular salivary glands in male mice had an extensive system of convoluted granular tubules (CGT), the cells of which contained EGF. When adrenaline or α‐phenylephrine was administered, the CGT cells degranulated, and there was a concomitant loss of intracellular EGF‐positive immunofluorescence. The excretory ducts were engorged with immunofluorescent material, indicating secretion of EGF into saliva, while the ductal cells themselves remained EGF‐negative. The degranulation response could be blocked by phentolamine, but not by propranolol, and no changes in EGF distribution followed the administration of pilocarpine. It was concluded that EGF is secreted, at least partly into the saliva, following an α‐adrenergic response, and that this occurs with degranulation of the cells of the CGT.
ULTRASTRUCTURAL EFFECTS OF THE VENOM OF THE SMALL‐SCALED SNAKE (PARADEMANSIA MICROLEPIDOTUS) ON THE NERVE TERMINALS OF THE RAT DIAPHRAGM
Authors: Hamilton RC , Broad AJ , Sutherland SK
Published: November 2007

Venom of the small‐scaled snake (Parademansia microlepidotus) causes a large increase in the number of coated omega figures inserted in the axolemma of nerve terminals. It also causes both a loss of synaptic vesicles and an increase in the number of neurofilaments in the nerve terminals. The actions of the venom are very similar to taipoxin, a pre‐synaptic neurotoxin from the venom of the taipan (Oxyuranus scutellatus). The morphological changes in the nerve terminals caused by the small‐scaled snake venom are not unusual and do not explain the extreme lethality of the venom.
EFFECT OF 5‐AZACYTIDlNE ON DNA METHYLATION IN EHRLICH'S ASCITES TUMOR CELLS
Authors: Tanaka M , Hibasami H , Nagai J , Ikeda T
Published: November 2007

5‐Azacytidine inhibited in vivo DNA methylation in Ehrlich's ascites tumor cells depending upon the dose at which 5‐azacytidine did not inhibit DNA synthesis significantly. This drug did not inhibit DNA methylation in vitro. The DNA methylase activity in ascitic cells decreased with the increasing dose of 5‐azacytidine. Hypomethylated DNA was obtained from the 5‐azacytidine treated ascitic cells.
THE EFFECT OF OVERNIGHT BILIARY DRAINAGE ON THE HEPATIC EXCRETION OF BROMOSULPHOPHTHALEIN
Authors: MacKinnon M , Kohler M
Published: November 2007

The excretion of bromosulphophthalein (BSP) was studied in rats after depletion of their bile salt pool by overnight biliary drainage. Peak biliary BSP excretion was significantly lower (80% of control value) in animals with a depleted bile salt pool; however, treatment with phenobarbital for 5 days before bile salt depletion prevented a reduction in BSP excretion. These studies support the observation that the hepatic excretion of bile salt is an important factor influencing the biliary excretion of BSP.
CUTANEOUS LEISHMANIASIS IN MICE: DISEASE PATTERNS IN RECONSTITUTED NUDE MICE OF SEVERAL GENOTYPES INFECTED WITH LEISHMANIA TROPICA
Authors: Mitchell Graham F , Curtis Joan M , Handman Emanuela , McKenzie Ian FC
Published: November 2007

BALB/c mice differ from CBA/H, (CBA/H × BALB/c)F1 and C57BL/6 mice in being highly susceptible to infection with a particular isolate of the intramacrophage protozoan parasite, Leishmania tropica. This is true over a wide range of challenge doses of promastigotes administered intradermally although, at low doses, male BALB/c are able to restrict the rate at which cutaneous lesions increase in size.

Resistance to infection in highly susceptible hypothymic nude (nu/nu) mice of CBA/H and C57BL/6 genotypes can be achieved readily with as few as 106 syngeneic lymphoid cells. In CBA/H.nu/nu mice, Lyl+2− cells in low dose cellular inocula appear to be involved in restoring resistance (i.e. rapid resolution of infection). Surprisingly, a proportion of BALB/c.nu/nu mice injected with syngeneic lymphoid cells are resistant and thus differ from intact BALB/c mice or non‐reconstituted BALB/c.nu/nu mice. In keeping with a high efficacy of limited numbers of T cells following minimal reconstitution, the majority of nude mice implanted subcutaneously with allogeneic, irradiated, neonatal thymus grafts are resistant to L. tropica infection. Genetic features of the node mouse, such as, a defect in skin, may contribute to the extraordinary potency of T cell reconstitutive manipulations. Evidence was obtained that BALB/c.nu/nu skin on BALB/c.nu/+ recipients did not support the development of lesions as readily as normal skin sites.
CELLULAR REQUIREMENTS FOR PRODUCTION AND RELEASE OF THE LYMPHOCYTE COSTIMULATOR
Authors: Andrus Linda , Lafferty Kevin J
Published: November 2007

The lymphocyte costimulator (CoS) is a lymphokine required for the activation of T cell reponses to H‐2 alloantigens or mitogen. CoS activity is found in the supernatant medium of Concanavalin A (Con A) stimulated spleen cells. In this paper we investigate the cellular requirements for CoS production by Con A‐activated mouse spleen cells. Maximal lymphokine production in response to Con A depends on a co‐operative interaction between T cells and a nylon wool‐adherent cell present in the spleen of nude mice. T cells appear to be the major producers of CoS activity, doing so only in response to an initial inductive stimulus supplied by nude spleen cells. The inductive stimulus is found as a soluble factor in the supernatant of Con A‐activated spleen cells, and can also be provided by stimulatory (S+), but not by non‐stimulatory (S−), tumour cells H‐2 identical with the responding T cells. The activation of lymphokine‐producing T cells is thus a two‐signal process, requiring both mitogen and an additional inductive signal. Once activated, homogeneous populations of T cells will release lymphokine in response to mitogen alone.
ALTERATIONS OF DRUG METABOLISM IN RATS EXPOSED TO CIGARETTE SMOKE
Authors: Farrell GC , Cooksley WGE , Cash GA , Powell LW
Published: November 2007

In male rats exposed to cigarette smoke, antipyrine clearance was enhanced to the same extent as has been observed in human cigarette smokers. The activity of aryl hydrocarbon hydroxylase, a representative microsomal mixed function oxidase, was increased significantly in lung and kidney of smoke‐exposed rats compared with controls. The activity of this enzyme in the liver, however, was not altered by cigarette smoke. Although aryl hydrocarbon hydroxylase activity in extrahepatic tissues was significantly enhanced after cigarette smoke exposure, the total drug metabolizing capacity of these tissues remained trivial compared with that of the liver. Hence, extrahepatic drug metabolism is unlikely to account for enhanced antipyrine elimination in cigarette smokers. The present study has established an animal model for studying the changes produced by cigarette smoke which result in enhanced drug metabolism in man.
FURTHER CHARACTERIZATION OF NATURAL KILLER CELLS INDUCED BY KUNJIN VIRUS
Authors: Macfarlan Roderick I , White David O
Published: November 2007

The natural killer (NK)* cell induced one to two days after Kunjin virus infection of BAI.B/c mice is cytotoxic for a wide range of syngeneic, allogeneic and xenogeneic cell lines. It is also weakly cytotoxic for some non‐malignant cells including mouse fibroblasts, macrophages and thymocytes, but not lymph node cells. Levels of lysis of non‐tumour target cells are dependent on their genotype. Furthermore, malignant cell lines may become resistant following transplantation in vivo then susceptible again after culture in vitro.

The virus‐induced NK cell is elicited as readily in athymic (nude) as in normal mice. X‐irradiation inhibits its development if administered prior to infection. It is labile on culture at 37°. The cell carries Fc receptors but its NK activity is not antibody‐dependent.
VASCULAR RESPONSES TO REN‐293 (2‐amino‐3[3, 5‐dihydroxyphenyl]‐1‐propanol hydrochloride)—A NEW SYMPATHOMIMETIC AGENT
Authors: Frost BR , Frewin DB
Published: November 2007

In this study the effects of REN‐293 have been examined on the rat tail artery ‘in situ’. It was found that the drug was totally dependent on the sympathetic nerves for its vasoconstrictor action. This action was blocked by phentolamine and attenuated by pre‐treatment of the vessel with tyramine. When a comparative study of the vasoconstrictor effects of several sympathomimetics was performed, it was found that REN‐293 was more potent than tyramine and ephedrine, but less so than etilefrine. It would appear that REN‐293 is of interest as a pharmacological tool for examining sympathetic nerve function, but its usefulness in the therapy of orthostatic hypotension is likely to be limited, due to the very indirect nature of its sympathomimetic action.
SUPPRESSOR CELL ACTIVITY IN A PROLIFERATIVE DISORDER OF T LYMPHOCYTES
Authors: Kupa Ann , Thomas Miriam E , Moore Helen , Bradley J , Zola H , Hooper M , Harding P
Published: November 2007

We report details of the immunological profile of a patient with the candidiasis endocrinopathy syndrome who has developed T‐type chronic lymphocytic leukaemia. The patient is anergic to a panel of delayed hypersensitivity skin tests, and has poor in vitro mitogenic responses, but B cell function in vivo is not impaired. Subsequent functional studies have revealed that cells from the patient have a significant suppressive effect in coculture (p < 0.05) on the responses of healthy donor lymphocytes (NR) to the mitogen phytohaemagglutinin (PHA). A degree of selectivity for the suppressive effect is suggested by the lack of similar effects on coculture responses to the mitogens cocanavalin A (Con A) and pokeweed mitogen (PWM). Mitomycin C treatment of the patient's cells reduced their suppressive activity but significant suppression was still observed in the majority of PHA cocultures. The suppressor activity required the presence of the pattern's cells in cocultures, as no suppression was observed when the pattern's serum or cell culture supernatant were included instead of the patient's cells in NR cultures.
COMPARISONS OF THE NEUROTOXIC ACTIVITY OF THE VENOM OF SEVERAL SPECIES OF FUNNEL WEB SPIDERS (ATRAX)
Authors: Atkinson RK
Published: November 2007

A bioassay has been developed to allow comparison of the neurotoxic activity of the venom of individuals of the four most common species of funnel web spiders (Atrax species). In the absence of purified Atrax neurotoxin, the stimulatory action of the venom on skeletal muscle from the cane toad, Bufo marinus, was compared with that of known concentrations of acetylcholine. Several experiments to validate the assay were performed, then venom samples from both male anti female spiders were assayed. It was found that individual female spiders of all Atrax species normally secreted several times as much venom as male spiders, but its neurotoxicity was extremely variable and generally much lower. Both sexes tended to secrete more potent venom in summer than in other seasons. Both also showed some decrease in venom volumes and potencies if repeatedly milked at short intervals. All four Atrax species were found to have approximately equal levels of neurotoxic activity.
A STUDY OF THE GROWTH REQUIREMENTS OF HUMAN TUMOUR CELLS IN TISSUE CULTURE
Authors: Rowbottom Lynette A , Whitehead RH , Roberts GP , Hughes LE
Published: November 2007

The effect of potential growth enhancing substances and other environmental factors on the growth of human cells in culture were examined, For all the cell lines tested the optimum pH range was 7·45‐7·55. Optimum osmolality varied with different cell lines, optimum values being 240 milliosmoles/kg for melanoma cell lines and foetal fibroblasts, 260 milliosmoles/kg for adult fibroblasts and 300 milliosmoles/kg for a breast cancer cell line. A number of hormones were found to affect the growth of the cell lines examined. Insulin and hydrocortisone enhanced the growth of all the tumour cells tested, whereas 17 β‐oestradiol enhanced the growth of breast cancer cells but inhibited the growth of melanoma cells and fibroblasts. Stilboestrol inhibited the growth of all the cell lines but prolactin enhanced the growth of melanoma cells and inhibited fibroblast cell growth. Addition of galactose to the medium stimulated the growth of all cell lines tested, whereas sucrose and Fructose resulted in stimulation of tumour cell growth but had little effect on fibroblasts. α‐thioglycerol and β‐mercaptoethanol enhanced the growth of the tumour cells but had little effect on the growth of fibroblasts. A modified medium has been formulated which enhanced the growth of all the cell lines used when compared with McCoy's 5A medium.
THE EXTENT OF REFLUX OF UNCONJUGATED 14C‐CHOLIC ACID FROM THE LIVER IN SUBJECTS WITH NORMAL LIVER FUNCTION
Authors: Collins DM , Bates JHT , Maslowski AH , McKinnon AE , Campbell CB
Published: November 2007

An improved understanding of bile acid physiology is a prerequisite for the construction of an acceptable model for describing plasma clearance of bile acids. The aim of this study was to determine the extent of reflux unconjugated cholic acid from the liver to the plasma in subjects with normal liver function. The clearance of a bolus injection of unconjugated 14 C‐cholic acid was studied in four subjects using samples collected simultaneously from a peripheral and a hepatic vein. Hepatic extraction ratios calculated directly from the data were found to be essentially constant dining the 20 min following injection, with average values of 0·60‐0·72. This indicates that reflux did not occur significantly in the subjects investigated. These results are interpreted as favouring a model in which exchange of unconjugated 14C‐cholic acid occurs between the plasma and a peripheral compartment with final removal from the plasma to the liver.
AGONIST‐STIMULATED BREAKDOWN OF MYO‐[2‐3H] INOSITOL‐LABELLED PHOSPHATIDYLINOSITOL IN MOUSE PANCREAS
Authors: Tennes Karin A , Roberts Michael L
Published: November 2007

Agonist‐stimulated hydrolysis of phosphatidylinositol (PI) in cell membranes has been proposed to lead to an increase of cytosol calcium concentration and activation of the cellular response in certain smooth muscles and glands.

A method is described which allows the rapid, reproducible measurement of hydrolysis of phosphatidylinositol in mouse pancreas. The technique involves the in vivo labelling of the pancreas with myo‐[2‐3H] inositol. The majority of the label incorporated into phospholipids is in the form of PI. with only a small proportion of label in di‐ and tri phosphoinositides. Tissue pieces of the labelled pancreata are incubated in vitro in the presence or absence of secretagogues, and the PI in homogenates of these pieces is precipitated with trichloroacetic acid. No PI remains in the acid‐soluble supernatant. This technique does not require the time‐consuming extraction and chromatographic separation of lipids which has been necessary in other assays of PI hydrolysis. Using this method, we have confirmed that PI breakdown is stimulated by carbachol and cholecystokinin‐octapeptide in the presence or absence of extracellular Ca2+. Agonist‐Stimulated hydrolysis of PI was potentiated by extracellular Ca2+, and was not dependent on agonist‐activated Na+ influx.

This technique will facilitate the investigation of the importance of PI breakdown in stimulus‐response coupling.
MECHANISMS OF RECOVERY AND ACQUIRED RESISTANCE IN LEWIS RAT EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
Authors: Willenborg David O
Published: November 2007

Experimental allergic encephalomyelitis in the Lewis rat is an acute, self‐limiting disease. Rechallenge of convalescent rats fails to induce disease. Previous experiments provided direct evidence against clonal deletion as the mechanism of recovery from disease and resistance to reinduction and suggested the operation of an active suppression mechanism. The present studies on the mechanism(s) of recovery and resistance suggest (1) resistance is a function of a systemic rather than a local suppressor mechanism, (2) suppression acts by inhibiting induction of immunity rather than expression of immunity and (3) recovery from disease can occur in the absence of detectable anti‐myelin basic protein antibodies, yet these antibodies may play a role in protection against reinduction of disease.
Autoimmunity since the 1957 clonal selection theory: a little acorn to a large oak
Authors: Mackay Ian R
Published: November 2007

Knowledge on autoimmunity is examined from the launch of clonal selection theory 1957–1959. Crucial elements then were ‘forbidden clones’ of immunocytes as agents of tissue damage, somatic mutations that generated such clones and ‘homeostatic mechanisms’ that controlled them. The understanding of autoimmunity over the succeeding 50 years has expanded immensely, and many more diseases now come under this rubric. Examined here are current problems of definition including ‘adaptive’ and ‘innate’ types of autoimmunity, estimations of population burdens of autoimmune diseases, the nature of autoepitopes in the context of the diabetes autoantigen GAD65, and the complexities of immune tolerance and the genetic influences thereon, leading to the nomination of multiple ‘tolerance/autoimmunity’ genes as critical components of pathogenesis. Burnet's concept of mutagenesis as a basic feature of various pathologies including autoimmunity is given a contemporary focus, his views on deletional tolerance have been well vindicated, his ‘forbidden clones’ remain as unphysiological as before albeit phenotypically resembling normal lymphocytes, and his ‘homeostatic mechanisms’ can be now interpreted in terms of immunoregulatory networks.
Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: Implications for function
Authors: Chattopadhyay Kausik , Ramagopal Udupi A. , Mukhopadhaya Arunika , Malashkevich Vladimir N. , DiLorenzo Teresa P. , Brenowitz Michael , Nathenson Stanley G. , Almo Steven C.
Published: November 2007

Glucocorticoid-induced TNF receptor ligand (GITRL), a recently identified member of the TNF family, binds to its receptor GITR on both effector and regulatory T cells and generates positive costimulatory signals implicated in a wide range of T cell functions. Structural analysis reveals that the human GITRL (hGITRL) ectodomain self-assembles into an atypical expanded homotrimer with sparse monomer–monomer interfaces. Consistent with the small intersubunit interfaces, hGITRL exhibits a relatively weak tendency to trimerize in solution and displays a monomer–trimer equilibrium not reported for other TNF family members. This unique assembly behavior has direct implications for hGITRL–GITR signaling, because enforced trimerization of soluble hGITRL ectodomain results in an ≈100-fold increase in its receptor binding affinity and also in enhanced costimulatory activity. The apparent reduction in affinity that is the consequence of this dynamic equilibrium may represent a mechanism to realize the biologically optimal level of signaling through the hGITRL–GITR pathway, as opposed to the maximal achievable level.
Changes in population characteristics and diet of Nile tilapia Oreochromis niloticus (L.) from Nyanza Gulf of Lake Victoria, Kenya: what are the management options?
Authors: Njiru M. , Okeyo-Owuor J. B. , Muchiri M. , Cowx I. G. , van der Knaap M.
Published: November 2007

Length frequency data collected from 1998 to 2001 from commercial landings was used to estimate asymptotic length (L∞), growth coefficient (K), mortality (Z, F, M), growth performance index (φ ′) and exploitation rate (E) of Oreochromis niloticus from the Nyanza Gulf of Lake Victoria, Kenya. Studies on the diet of O. niloticus collected by demersal trawl and seining between 1998 and 2000 were also conducted.

Length frequency data were analyzed using the FISAT software (an FAO-ICLARM Stock Assessment Tool package). The L∞ had a mean value (± S.D) of 58.78 ± 2.42 cm TL, K of 0.59 ± 0.05 yr− 1, Z of 2.16 ± 0.40 yr− 1, M of 1.00 ± 0.06 yr−1, F of 1.12 ± 0.34 yr−1, E of 0.48 ± 0.11 and φ ′ of 3.31 ± 0.04. Length at first entry into the fishery (L50) was observed at 26.18 ± 12.50 cm TL. Recruitment occurred throughout the year, with two peaks corresponding with the rainy seasons.

A comparison with previous studies in the gulf indicates that O. niloticus is now caught at a smaller mean size, whereas K, Z, and M have increased. Fish appeared to become sexually mature at a smaller size.

Nile tilapia originally known to be herbivorous, feeding mostly on algae, has diversified its diet to include insects, fish, algae and plant materials, all being important food items. The changes in population characteristics and diet of O. niloticus are discussed in context of changes occurring in the lake and its surroundings.
Adenovirus RIDα regulates endosome maturation by mimicking GTP-Rab7
Authors: Shah Ankur H. , Cianciola Nicholas L. , Mills Jeffrey L. , Sönnichsen Frank D. , Carlin Cathleen
Published: November 2007

The small guanosine triphosphatase Rab7 regulates late endocytic trafficking. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are guanosine triphosphate (GTP)–Rab7 effectors that instigate minus end–directed microtubule transport. We demonstrate that RILP and ORP1L both interact with the group C adenovirus protein known as receptor internalization and degradation α (RIDα), which was previously shown to clear the cell surface of several membrane proteins, including the epidermal growth factor receptor and Fas (Carlin, C.R., A.E. Tollefson, H.A. Brady, B.L. Hoffman, and W.S. Wold. 1989. Cell. 57:135–144; Shisler, J., C. Yang, B. Walter, C.F. Ware, and L.R. Gooding. 1997. J. Virol. 71:8299–8306). RIDα localizes to endocytic vesicles but is not homologous to Rab7 and is not catalytically active. We show that RIDα compensates for reduced Rab7 or dominant-negative (DN) Rab7(T22N) expression. In vitro, Cu2+ binding to RIDα residues His75 and His76 facilitates the RILP interaction. Site-directed mutagenesis of these His residues results in the loss of RIDα–RILP interaction and RIDα activity in cells. Additionally, expression of the RILP DN C-terminal region hinders RIDα activity during an acute adenovirus infection. We conclude that RIDα coordinates recruitment of these GTP-Rab7 effectors to compartments that would ordinarily be perceived as early endosomes, thereby promoting the degradation of selected cargo.
NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte nucleus
Authors: Lancaster Oscar M. , Cullen C. Fiona , Ohkura Hiroyuki
Published: November 2007

Accurate chromosome segregation in meiosis requires dynamic changes in chromatin organization. In Drosophila melanogaster, upon completion of recombination, meiotic chromosomes form a single, compact cluster called the karyosome in an enlarged oocyte nucleus. This clustering is also found in humans; however, the mechanisms underlying karyosome formation are not understood. In this study, we report that phosphorylation of barrier to autointegration factor (BAF) by the conserved kinase nucleosomal histone kinase-1 (NHK-1; Drosophila Vrk1) has a critical function in karyosome formation. We find that the noncatalytic domain of NHK-1 is crucial for its kinase activity toward BAF, a protein that acts as a linker between chromatin and the nuclear envelope. A reduction of NHK-1 or expression of nonphosphorylatable BAF results in ectopic association of chromosomes with the nuclear envelope in oocytes. We propose that BAF phosphorylation by NHK-1 disrupts anchorage of chromosomes to the nuclear envelope, allowing karyosome formation in oocytes. These data provide the first mechanistic insight into how the karyosome forms.
Prenatal administration of vitamin A alters pulmonary and plasma levels of vascular endothelial growth factor in the developing mouse
Authors: Pinto Maria de Lurdes , Rodrigues Paula , Coelho Ana Cláudia , Pires Maria dos Anjos , Santos Dario Loureiro dos , Gonçalves Carlos , Bairos Vasco António
Published: November 2007

Vitamin A and the retinoids play a unique role in mammalian embryonic and foetal development and are essential for both cellular differentiation and the establishment of normal morphogenesis. Vascular endothelial growth factor (VEGF) is a known potent mitogenic factor that plays a key role in lung development and function maintenance. In order to contribute to a better knowledge of the modulating effects of vitamin A in lung development, we investigated the effects of the antenatal administration of vitamin A on VEGF expression in lungs and plasma from foetuses and neonates. Pregnant mice were subjected to subcutaneous administration of vitamin A on the 12th gestational day. The lungs and plasma from foetuses and neonates were collected daily from the 15th gestational day till the day of birth. Our results show that vitamin A modulates VEGF concentrations both in lungs and plasma. Statistically significant differences were observed at gestational days 15 (P = 0.004 for lungs; P < 0.0001 for plasma), 16 (P < 0.0001 for lungs and plasma) and 18 (P < 0.0001 for lungs; P < 0.05 for plasma). Vitamin A tends to increase the expression of this factor in the lung, particularly during the critical period of perinatal adaptation to postnatal life. These effects seem to be spatial and temporally regulated, and point out to the important role of vitamin A during lung development.
Staffing adequacy, supervisory support and quality of care in long‐term care settings: staff perceptions
Authors: Räikkönen Outi , Perälä Marja‐Leena , Kahanpää Anja
Published: November 2007

Title.  Staffing adequacy, supervisory support and quality of care in long‐term care settings: staff perceptions

Aim.  This paper is a report of a study to explore relationships between perceived care quality, self‐assessed professional skills, and the perceptions of the quality‐related factors.

Background.  The work in long‐term care is more demanding than in the past. The quality of care is strongly related to the well‐being and job satisfaction of staff. Those emerge in part through a perception of resources allocated to caring and also through a perception of the quality achieved.

Method.  Data were collected in Finland in 2002 using a questionnaire sent to the nursing staff working in 112 wards in 40 long‐term care institutions monitoring their care with the Resident Assessment Instrument System. Institutions were invited to participate the survey. The response rate was 70·2% (n = 1262). The respondents represented 3·8% of nursing personnel working in long‐term care institutions.

Findings.  Staff members who perceived staffing levels as inadequate and supervisory support as insufficient had lower perceptions of their own professional skills and the quality of care. Perceptions of empowering support behaviour were more strongly associated to self‐assessed skills and to perceived care quality than perceptions of skills‐oriented support activities.

Staff members with short professional training, older staff members and staff members with long work experience in the unit had lower perceptions of their professional skills than other groups.

Conclusion.  The perception of adequate staffing and of sufficient supervisory support, especially empowering support increases the probability of perceiving the care quality as good. If supervisors concern themselves with staff members’ perceptions, they can better identify the staffing needs and also the support needs of personnel.
Buoyancy‐driven deformation and contemporary tectonic stress in the lithosphere beneath Central Italy
Authors: Aoudia A. , Ismail‐Zadeh A. T. , Romanelli F.
Published: November 2007

We studied the continental deformation and modelled the contemporary flow and stress distribution in the lithosphere beneath Central Italy. We made use of a revisited crust and uppermost mantle Earth structure that supports delamination processes. The model behaviour is primarily determined by the thick high density lithospheric root to the east and the low‐viscosity shallow mantle wedge to the west. The rate of the modeled crustal motion is in agreement with GPS data and the pattern of lithospheric flow explains the heat flux, the regional geology and provides a new background for the genesis and age of the recent Tuscan magmatism. The modelled stress in the lithosphere is spatially correlated with the prevailing stress field and the gravitational potential energy patterns and shows that buoyancy forces, solely, can explain the coexisting regional contraction and extension and the unusual sub‐crustal seismicity.
Female coloration indicates female reproductive capacity in blue tits
Authors: DOUTRELANT C. , GRÉGOIRE A. , GRNAC N. , GOMEZ D. , LAMBRECHTS M. M. , PERRET P.
Published: November 2007

It is poorly understood whether female morphological and behavioural traits can be used as ‘signals’. In particular, experimental tests of the hypothesis that female ornaments reflect quality are scarce. Here, we experimentally examine whether female plumage coloration might signal maternal quality in the blue tit, Cyanistes caeruleus by forcing half of the females breeding in our population to produce a replacement clutch. Using statistical models that controlled for the effects of male coloration, and the effects of age and condition of both parents, we found that carotenoid‐based female coloration was positively linked to key proxies of bird lifetime reproductive success: clutch size, fledgling success and recruitment. Importantly, the relationships between maternal yellow carotenoid coloration and both clutch size and recruitment were stronger in the experimental group than in the control group, indicating that breeding females with higher values of yellow coloration were better able to handle the cost of producing a second clutch. Finally, UV‐blue female coloration was positively linked to female survival and marginally linked to laying date. Taken together, these results show for the first time in a natural population that female coloration can indicate individual and maternal quality under natural and adverse reproductive conditions. They highlight the potential for the evolution of female ornamental traits through sexual selection.
Coevolution and the adaptive value of autumn tree colours: colour preference and growth rates of a southern beech aphid
Authors: RAMÍREZ C. C. , LAVANDERO B. , ARCHETTI M.
Published: November 2007

The evolutionary explanation for the change in leaf colour during autumn is still debated. Autumn colours could be a signal of defensive commitment towards insects (coevolution) or an adaptation against physical damage because of light at low temperatures (photoprotection). These two hypotheses have different predictions: (1) under the coevolution hypothesis, insects should not prefer red leaves in autumn and grow better in spring on trees with green autumn leaves; and (2) under the photoprotection hypothesis, insects should prefer and grow better on trees with red leaves because they provide better nutrition. Studying colour preference in autumn and growth rates in spring of a southern beech aphid species (Neuquenaphis staryi) on Nothofagus alessandrii, we found preference for green leaves in autumn but no differential performance of aphids in spring. We suggest that aphid preference for green might have evolved to exploit better their host during the autumn rather than to improve their performance in spring.
Sibutramine‐associated adverse effects: a practical guide for its safe use
Authors: Florentin M. , Liberopoulos E. N. , Elisaf M. S.
Published: November 2007

Obesity is a multifactorial chronic disorder which comprises a serious health problem nowadays. The effective management of obesity is difficult in contemporary societies where abundance of hypercaloric food and sedentary lifestyle is the rule. Apart from lifestyle interventions, which include diet, exercise and behavioural treatment, weight‐loss medications can also be used for the management of obesity. Sibutramine, a selective monoamine reuptake inhibitor, is a drug with established efficacy in sustained weight reduction and an overall favourable safety profile. However, its action on the sympathetic nervous system has linked sibutramine to blood pressure and heart rate elevations. These potentially adverse effects as well as other sibutramine‐associated side effects and their possible underlying mechanisms are reviewed in the present article. Compelling evidence from the majority of data in the literature shows that sibutramine can be effectively used in conjunction with caloric restriction and exercise in obese patients. Hypertension, if adequately treated and frequently monitored, is not an absolute contraindication for the prescription of sibutramine.
‘WALKING FOR PLEASURE’? BODIES OF DISPLAY AT THE MANCHESTER ART‐TREASURES EXHIBITION IN 1857
Authors: LEAHY HELEN REES
Published: November 2007

The scale, ambition and, arguably, the art‐historical significance of the Art‐Treasures Exhibition held in Manchester in 1857 was unprecedented in Britain, and has not been equalled subsequently. In all over 16,000 works of art were gathered together in the Art‐Treasures Palace at Old Trafford, and when the exhibition closed after five months, over 1,300,000 visitors had passed through its turnstiles. Prince Albert officially approved the venture on condition that the exhibition would provide more than the ‘mere gratification of public curiosity’ and should instead ‘enable, in a practical way the most uneducated eye to gather the lessons which ages of thorough and scientific research have attempted to abstract’. In effect, a wide and inclusive public was being invoked via the familiar metonymic substitution of the ‘eye’ for the person of the spectator and yet it was the quantity and conduct of visitors walking, looking and consuming bodies that provoked a stream of commentary and debate, and that constituted an unofficial register of the exhibition's success. Recovery of the experiences and observations of the ‘social body’ of the exhibition shows that neither the coded messages of the display schema nor the example set by prestigious visitors were able to direct the behaviour and aesthetic responses of many spectators. In that sense, the practices and public of the Art‐Treasures Exhibition were very specific to the conditions of mid‐nineteenth‐century Manchester, yet stand as a salutary example to exhibition historians and curators today.
RELATIVISM, COMMENSURABILITY AND TRANSLATABILITY
Authors: Glock Hans‐Johann
Published: November 2007

This paper discusses conceptual relativism. The main focus is on the contrasting ideas of Wittgenstein and Davidson, with Quine, Kuhn, Feyerabend and Hacker in supporting roles. I distinguish conceptual from alethic and ontological relativism, defend a distinction between conceptual scheme and empirical content, and reject the Davidsonian argument against the possibility of alternative conceptual schemes: there can be conceptual diversity without failure of translation, and failure of translation is not necessarily incompatible with recognizing a practice as linguistic. Conceptual relativism may be untenable, but not for the hermeneutic reasons espoused by Davidson.
Reintegration Support for Young Ex‐Combatants: A Right or a Privilege?
Authors: Peters Krijn
Published: November 2007

Under‐age and youthful combatants are the major participants in contemporary African conflicts and, therefore, the largest group to be disarmed, demobilized and reintegrated when peace agreements are signed. Programmes to support this process, so‐called disarmament, demobilization and reintegration (DDR) programmes, usually have two main objectives: 1) to reduce security risks; and 2) make ex‐combatants less dependent upon their home communities once returned. However, badly designed or implemented DDR programmes can jeopardize a country's fragile peace and rehabilitation process.

This article uses the Sierra Leone case to explore the efficacy of DDR programmes. It questions whether the reintegration options offered to the demobilized ex‐combatants were appropriate to the context. In a country where more than 70 per cent of the population depends on (semi‐)subsistence agriculture, the most popular reintegration package among the young ex‐combatants was vocational training ‐ only 15 per cent of the ex‐combatants chose the “agricultural package”. The article questions whether young ex‐combatants are simply disinterested in farming, and, if so, whether vocational skills training programmes offer realistic alternative livelihood opportunities.

This article argues that most ex‐combatants have not been able to achieve sustainable livelihoods skills due to failures in DDR programmes. The existence of a large reservoir of marginalized, foot‐loose youth has been widely acknowledged as one of the root causes of the conflict in Sierra Leone. There is clear evidence that one result of the poor DDR design and implementation is that this reservoir has not been sufficiently drained in Sierra Leone.