bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONVERSION OF AZATHIOPRINE INTO MERCAPTOPURINE AND MERCAPTOIMIDAZOLE DERIVATIVES IN VITRO AND DURING IMMUNOSUPPRESSIVE THERAPY
Authors: Chalmers AH , Knight PW , Atkinson MR 
Published: December 2007

SummaryA spectrophotometric method was used to show that azathioprine (“Imuran”, BW 57–322) is converted into 6‐mercaptopurine by a second‐order reaction with glutathione. In the pH range studied (6·85·8·45), at 37° in 50 mM phosphate, the rate of formation of 6‐mercaptopurine is given by the expression: d[6‐mercaptopurine]/dt “0·32 (pH‐6·6) [azathioprine] [glutathione] mole sec.−1 litre−1. The results were applicable to the formation of 6‐mercaptopurine from azathioprine and glutathione in plasma. The half‐time for conversion of azathioprine into 6‐mercaptopurine at pH 7·35 and 37° in the presence of 1 mM glutathione was 47 min.At pH values above 10 formation of 5‐mercapto‐1‐methyl‐4‐nitroimidazole from azathiopries was observed in vitro. The mercaptoimidazole was detected in the urine of patients after oral doses of azathioprine. A spectrophotometric assay after fractionation on Sephadex G‐15 was used to follow the time‐course of excretion of the imidazole.Net conversion of azathioprine into 6‐thiouric acid after treatment with azathioprine was followed by a spectrophotometric assay involving co‐precipitation of urinary 6‐thiouric acid with uric acid. The time‐course of urinary 6‐thiouric acid excretion was similar to that of the mercaptoimidazole, and is consistent with the rates of azathioprine cleavage observed in vivo. These metabolites were mainly excreted within 8 hr. of an oral dose of azathioprine.The relevance of these results to the action of azathioprine and to improvements in control of its clinical use are discussed.
THE ORIGIN OF THE ANTIBODY RELEASED INTO SERUM FOLLOWING INJECTION OF BACTERIAL LIPOPOLYSACCHARIDE
Authors: Hill WC , Rowley D 
Published: December 2007

SummaryIncreased levels of certain antibodies were detected in the serum of guinea‐pigs about 24 hr, after being injected with bacterial lipopolysaccharide. These antibodies were found to have been presynthesized and released, rather than having been synthesized subsequent to the lipopolysaccharide injection. Simple calculations show that at least 10 times as much antibody is present in the serum. If this store is inside the antibody‐forming cells then the intracellular concentration of antibody must be about one million‐fold greater than the serum concentration.
THE CATECHOLAMINES IN THE CENTRAL ARTERY OF THE RABBIT EAR
Authors: de la Lande IS , Head RJ 
Published: December 2007

SummaryFluorimetric assay of the central artery of the rabbit ear yielded mean noradrenaline and adrenaline contents of 0·89 and 0·08 μg./g. respectively. This finding is consistent with previous histochemical observations and tends to exclude the possibility that adrenaline is of importance in neurotransmission in the rabbit ear.
STUDIES ON CYTOPHILIC ANTIBODIES.
Authors: Nelson DS , Mildenhall P 
Published: December 2007

SummaryNon‐inbred Swiss mice were immunized by intraperitoneal or sub‐cutaneous injections of sheep erythrocytes in saline. Freund's incomplete adjuvant or Freund's complete adjuvant. Titrations were made of macrophage cytophilic antibodies. complement‐fixing (immune adherence) antibodies and direct haemagglutinating antibodies in sera obtained at weekly intervals up to 4 weeks. Early and delayed hypersensitivities were estimated by footpad tests with sheep erythrocytes. When the intraperitoneal route of immunization was used, cytophilic antibodies and delayed‐type hypersensitivity developed consistently only after the erythrocytes had been injected in Freund's complete adjuvant. When the subcutaneous route was used, cytophilic antibodies and delayed‐type hypersensitivity developed after the erythrocytes had been injected in complete or incomplete adjuvant but not after they had been injected in saline. There was a correlation between the intensity of delayed (48 hr.) footpad reactions and the levels of cytophilic antibodies in serum as well as between the intensity of early (4 hr.) reactions and the levels of complement‐fixing antibodies. A second injection of antigen in saline (footpad test) was usually followed by a rise in titre or by the reappearance, or even by the first appearance, of cytophilic antibodies in the serum. Cytophilic antibodies could appear in the absence of detectable complement‐fixing antibodies and vice versa, and there was overall no correlation between the levels of cytophilic and complement‐fixing antibodies in the sera.
THE ZINC CONTENT OF RAT MAST CELLS
Authors: Angyal Annette M , Archer GT 
Published: December 2007

SummaryThe zinc content of isolated rat mast cells was estimated by atomic absorption spectrophotometry. The mast cells were harvested by peritoneal lavage and separated from other peritoneal cavity cells by density gradient centrifugation. The zinc content of large mast cells was found to be 2·1 μg. Zn/106mast cells (standard error ± 0·23) and 40 times greater than the zinc content of other cell types. Small immature mast cells were found to contain less zinc than mature mast cells. Significant amounts of zinc were released from mast cells by freezing and thawing but not by hypotonic lysis.
THE MORPHOLOGY OF ANTIBODY‐FORMING CELLS IN THE MOUSE
Authors: Cunningham AJ 
Published: December 2007

SummaryThe popliteal lymph nodes of mice were antigenically stimulated with sheep erythrocytes, and the changing numbers of cells releasing 19S or 7S haemolytic antibody were assayed using a modification of the Jerne‐Ingraham plaque technique. For the first 2–3 days after primary immunization, no plaque‐ forming cells could be found in these nodes. A rapid rise in the number of cells releasing 19S antibody followed during the next 3 days. By 6 days cells producing 7S antibody began to appear, reaching peak numbers at about 12 days. From this time on, and throughout the secondary response, cells producing 7S antibody were much more numerous in the nodes than those releasing 19S haemoloysin.At all stages of primary and secondary immune responses, individual plaque‐ forming cells producing antibody of either type were isolated, smeared individually and examined by light microscopy. A wide variety of morphological types was found. A small proportion of plaques was produced by classical mature plasma cells, but most antibody‐forming cells were basophilic mono nuclears with relatively little cytoplasm. The smaller members of this series would probably be indistinguishable from small lymphocytes in preparations of living or fluorescence‐stained cells. No consistent morphological differences were observed between cells releasing 19S or 7S antibody.Thirteen plaque‐forming cells from the spleens of unimnunized mice have also been characterized. Six of these were lymphocytes, 6 were rather small basophilic mononuclear cells and 1 was classed as an atypical plasma cell.
PLANTAR ULCERS OCCURRING AFTER NEURECTOMY: A LIGHT AND ELECTRON MICROSCOPE STUDY
Authors: Barton AA , Barton Mary 
Published: December 2007

SummarySeverance of the tendo‐calcaneus or division of the sciatic nerve caused ulcers to appear on the heels of mice within 6 hr. of operation. This was due to thrombosis of capillaries in the subcutaneous tissues, resulting from a disorder of posture. The lumen of the capillaries was filled with a thrombus of platelets and lysed red cells. The endothelial cells were contracted and separated from one another. Division of sensory nerves did not cause ulceration, nor did division of the sciatic nerve alter ulcers due to tenotomy. It was concluded that nerves did not serve a trophic function. The relation of these ulcers to decubitae and the plantar ulcers of leprosy is discussed.
THE MEDIATION OF INCREASED VASCULAR PERMEABILITY IN INFLAMMATION
Authors: Muller HK , Salasoo I , Wilhelm DL 
Published: December 2007

SummaryRabbit serum contains a permeability factor which increases vascular permeability in the homologous species for periods up to 4 hr. Such prolonged permeability effects contrast markedly with those of other endogenous factors, which increase permeability for only about 10–20 min.When rabbit serum is fractionated in ethyl ether or ethanol systems, the permeability factor is mainly concentrated in preparations containing α‐ and β‐globulins. Tested in animals with circulating Evans′ blue, the permeability factor has an activity in 1‐hr. lesions that increases as much as 280‐fold in the ensuing 3 hr.The duration of increased permeability is best demonstrated by the injection of intravenous dye in animals already bearing lesions of varying ages. Tested by this technique, rabbit permeability factor induces a maximal increase of vascular permeability in 1½–2½ hr., normal low permeability being restored in 4 hr.On a weight basis relative to histamine, the most active preparations at this stage of the work have a permeability factor potency of 0·3 the dosage‐ response lines having a slope of 4·4–6·3.
QUANTITATIVE ASSESSMENT OF THE PERSISTENT ANTIMITOTIC EFFECT OF CERTAIN HEPATOTOXIC PYRROLIZIDINE ALKALOIDS ON RAT LIVER
Authors: Downing DT , Peterson JE 
Published: December 2007

SummaryThe burst of mitosis in liver cells after partial hepatectomy is inhibited by certain pyrrolizidine alkaloids given prior to operation. Thus, intraperitoneal injection of 0·05 acute LD50 of heliotrine into rats up to 8 weeks before partial hepatectomy resulted in a 50% inhibition of mitosis as measured 8 hr. after the administration of a dose of colchicine.Heliotrine, lasiocarpine and lasiocarpinc N‐oxide given four weeks before operation produced maximal antimitotic effect when given in a single dose greater than about 0·1 acute LD50 and a graded response at lower dose levels. Heliotridine, 7‐angelythcliotridine and platyphylline showed no significant activity.A bioassay procedure based on these findings is proposed, which is suitable for determination of the specific antimitotic activity of compounds capable of producing persistent inhibition of liver cell division.
POTASSIUM CONTRACTURES IN THE URETER OF THE GUINEA‐PIG
Authors: Chapman JB , Holman Mollie E 
Published: December 2007

SummaryThe electrical and mechanical responses of the guinea‐pig ureter to raised extracellular potassium ion concentrations hove been studied.The response consisted of an initial series of rapid contractions associated with action potentials followed by the development of maintained tension associated with maintained depolarization. Relaxation and repolarization occurred when normal potassium ion concentration was restored. The threshold potassium ion concentration for the development of maintained tension varied between 25 and 50 mM.The amplitude of the maintained tension could be immediately and reversibly changed by varying the external calcium ion concentration, though the calcium ion concentration at which these changes appeared varied considerably between preparations. Absence or reduction of the initial contractions in low calcium ion solutions was always accompanied by absence or abnormality of the action potential.It is suggested that the maintained tension depends on an increased influx of extracellular calcium ions during the potassium ion‐induced depolarization. Although this mechanism is not excluded as a possible basis for contraction initiated by the depolarization of the action potential, it is likely that a calcium ions “store” of unknown nature is involved in the normal excitation‐contraction coupling process.
THE EFFECTS OF OCCLUSION OF THE BLOOD SUPPLY TO THE POPLITEAL LYMPH NODE OF THE RABBIT ON THE CELL AND PROTEIN CONTENT OF THE LYMPH AND ON THE HISTOLOGY OF THE NODE
Authors: Osogoe B , Courtice FC 
Published: December 2007

SummaryThe anatomical arrangement of the blood vessels supplying the popliteal lymph node of the rabbit was determined by injecting latex into the femoral artery and vein. Complete occlusion of its blood supply caused no appreciable change in the flow and protein concentration in afferent and efferent lymph of the node.The cell count in the efferent lymph fell from 6th hr. to 5th day after occlusion to levels approaching those in afferent lymph, and during this time degeneration of cells within the node occurred except for small areas adjacent to the marginal and medullary sinuses.Regeneration of the lymphatic tissue with an increase in the cell counts of the efferent lymph began from about the 7th day after occlusion and was due to the regeneration of blood vessels connected with the blood circulation outside the node.In experiments, in which one or more small collateral arteries were left intact, no degeneration of the cells or reduction in cell content of the lymph occurred.
CELLULAR LOCALIZATION OF 125I‐LABELLED SALMONELLA ADELAIDE FLAGELLIN FOLLOWING INJECTION INTO THE RAT IN THE PRESENCE OF FREUND'S COMPLETE ADJUVANT
Authors: Lind Patricia E 
Published: December 2007

SummaryA comparison has been made of the uptake of 125I‐labelled flagellin in the pepliteal lymph nodes following its injection into the foot‐pad of the rat in aqueous solution and in Freund's complete adjuvantIn aqueous solution the cellular localization of the antigen within the node was found to follow the characteristic pattern previously described by Ada, Nossal and Austin (1964) with high concentrations of label appearing in the medullary macrophages and over the lymphoid follicles of the cortex.Antigen injected in adjuvant persisted for a long period both at the injection site and in the draining lymph node. Only minimal follicular localization of the antigen was observed within the node. Instead large amounts of label were found to accumulate in the subcapsular sinus and from this source, relatively small aggregates of label associated with droplets of lipid from the adjuvant appeared to migrate slowly and randomly into the body of the node. This process was accompanied by lymph node hyperplasia associated principally with a massive plasma Cell proliferation in the medullary area. At the same time high titres of circulating antibody developed.It has been postulated that antigen taken up by the reticular dendritic web of the cortical lymphoid follicles, following its injection in aqueous solution, may act as an antigen depot with which antigen‐sensitive precursors of antibody‐ producing cells may make contact and receive their specific inductive stimulus. It is further suggested that, when antigen is Injected in Freund's complete adjuvant, not only does the adjuvant stimulate intensive lymphoid cell proliferation within the draining lymph nodes with a probable increase in the number of antibody‐producing cell precursors, but that the antigen in the antigen‐ adjuvant droplets which reach the interior of the node, both in quantity and persistence, may fulfil more efficiently the role played by antigen on the reticulum cells of the cortical follicles.
THE ROLE OF ALDOSTERONE IN RENAL SODIUM CONSERVATION DURING SODIUM DEPLETION
Authors: Blair‐West JR , Coghlan JP , Denton DA , Scott D , Wright RD 
Published: December 2007

SummaryThe effect of aldosterone infused intravenously at 2, 4, 8 and 16 μg./hr., i.e. over the physiological range, upon the renal retention of sodium was studied in adrenalectomized sheep during progressive sodium depletion over 32 hr. via a parotid fistula. The animals were given basal cortisol and corti‐costerone. The resulting patterns of renal sodium excretion were compared with the renal response to sodium loss in the same animals before bilateral adrenalectomy. With high renal output of sodium under high sodium load there was no evidence of aldosterone activation of sodium retention, but as sodium loss progressed there was evidence of increased sensitivity to aldosterone of the renal sodium retention mechanism. The dose/effect relation between rate of aldosterone infusion and renal excretion of sodium at this stage showed (a) a threshold dosage for this effect, (b) a proportionality between dosage and degree of sodium retention, (c) that the effective dosage is similar to the aldosterone secretion rate from the adrenal when present under similar circumstances of sodium toss. The results demonstrate that the normal rate of release of aldosterone in the sodium replete animal, 0·64 ± 0·36 ± 0·10 (14) μg./hr, is not sufficient to allow a maximal sodium retention by the kidney. Therefore, aldosterone secretion is commensurate and causal to normal renal sodium conservation during sodium loss.
THE EFFECTS OF ALPHA‐ADRENERGIC RECEPTOR BLOCKADE AND SYMPATHETIC DENERVATION ON THE PRESSOR ACTION OF ANGIOTENSIN IN MAN
Authors: Scroop GC , Whelan RF 
Published: December 2007

SummaryIntravenous phentolamine abolished the sympathetically‐mediated hand vasoconstriction which occurs during intravenous infusions of angiotensin in normal subjects. However, the blood pressure response was not significantly modified, indicating that the sympathetic stimulating action of angiotensin, in the doses and duration of exposure used, did not make a major contribution to the overall increase in peripheral resistance.This conclusion is supported by the observation of enhanced pressor responses to angiotensin in two patients with autonomic nervous system degeneration and in one patient with complete cervical cord transection.The failure of phentolamine to modify the pressor response to angiotensin indicates that with the doses used adrenal medullary release of catecholamines, which is known to occur in animals during angiotensin infusions, does not make a significant contribution to the pressor response in man.
INTERACTIONS BETWEEN ANGIOTENSIN, NORADRENALINE AND SEROTONIN ON THE PERIPHERAL BLOOD VESSELS IN MAN
Authors: Scroop GC , Walsh JA 
Published: December 2007

SummaryThe constrictor action of noradrenaline on the hand vessels was significantly enhanced in the presence of threshold amounts of angiotensin as was that of angiotensin in the presence of threshold amounts of serotonin. No such potentiation was seen with the same combinations in the forearm.In the forearm significant potentiation was only seen with constrictor doses of noradrenaline in the presence of threshold amounts of serotonin. No potentiation was seen with this combination in the hand vessels.Although statistically significant potentiation was seen with all three possible combinations of the drugs, it was not common to both vascular beds studied. Furthermore, it was often of a minor degree and inconsistent within the one combination. These considerations make it unlikely that these interactions are of biological importance in man.
PATTERNS OF MIGRATION OF LYMPHOID CELLS
Authors: Austin Caroline M 
Published: December 2007

SummaryStudies in inbred Lewis rats have shown that primary lymphoid follicles are within the pathway or traffic area of lymphoid tissue, both in the spleen and in regional lymph nodes. Suggestive evidence is given for antigenic stimulation causing blast cell transformation within these follicles.The studies have been performed using cells labelled with 3H‐thymidine in vitro or 3H‐uridine in vivo. Cells cultured with 3H‐uridine in vitro were those of the peripheral lymphoid organs. In vivo labelling was carried out using parabiosed animals.Marked overall differences in the pattern of movement of these different populations of cells have been annotated. The majority of cells labelled with 3H‐uridine are found in the diffuse cortex of the nodes or the periarteriolar lymphocyte sheath of the spleen. However, when cells are labelled with 3H‐ thymidine there is a fairly even distribution throughout the different compartments of the lymphoid organs. Thus, young lymphocytes show a different migratory pattern to the bulk of the population.
COLONY GROWTH OF RAT BONE MARROW CELLS IN VITRO
Authors: Bradley TR , Siemienowicz R 
Published: December 2007

SummaryA method is described which is suitable for the growth of colonies from rat bone marrow cells in vitro. The method involves plating out rat marrow cell suspensions in agar, using small amounts of rat serum as the stimulus to colony growth. Dose response relationships are shown to exist between the dose of rat serum used and the number of colonies produced and between the number of marrow cells plated and the number of colonies produced. Thus, the system is suitable for quantitative work with rat marrow cells. The nuclear morphology of cells in the colonies is described. The colonies initially consisted of cells with ring‐shaped nuclei but showed a transition to large mononuclear cells later in the incubation period.
STIMULATION OF MOUSE BONE MARROW COLONY GROWTH IN VITRO BY CONDITIONED MEDIUM
Authors: Bradley TR , Sumner Margaret A 
Published: December 2007

SummaryIncubation of culture medium with cells from 8‐day‐old mouse kidney or cells from 16‐ to 18‐day mouse embryos resulted in production of conditioned medium which was capable of stimulating colony growth in vitro of mouse bone marrow cells.A linear relationship was demonstrated between the dose of conditioned medium and the number of colonies developing. A similar relationship was also found between conditioned medium dosage and the size of the colonies grown.The activity of conditioned medium was not lost on extensive dialysis; it showed a high degree of heat stability and was precipitated by 50‐100 saturation with ammonium sulphate.The morphology of cells in colonies grown with conditioned medium was typical of mouse metamyelocytes early in the incubation period but later there was a transition to mononuclear cell types.
TUBERCULIN SENSITIVE LYMPHOCYTES IN HUMAN PERIPHERAL BLOOD FOLLOWING MANTOUX TEST
Authors: Hughes Norman R 
Published: December 2007

SummaryIn two series of peripheral blood leucocyte cultures taken from a Mantoux positive donor it was found that following tuberculin (P.P.D) injections there were (1) increases in the number of cultured lymphocytes responding to P.P.D. by transformation to blast cells, and (2) decreases in the number of macrophages attaching to cover slips in the presence of P.P.D.
THE MOVEMENT OF POTASSIUM IONS ACROSS THE UTERINE MUCOSA OF THE RAT
Authors: Lopata A 
Published: December 2007

SummaryIn the group of prooestrus rats examined the fluid which collected in the uterine lumen contained a high concentration of potassium ions.It was shown that during prooestrus and oestrus the potassium ions in the luminal fluid penetrate the endometrial mucosa and enter the uterine wall. The maximum amount of endometrial or myometrial potassium ions, derived from the luminal fluid, occurred during late prooestrus.
BINDING OF SULFHYDRYL REAGENTS TO NORMAL AND IRRADIATED LEUCOCYTE LYSOSOMES
Authors: Harris JW 
Published: December 2007

SummaryThe cytoplasmic granules (lysosomes) of leucocytes are highly reactive in situ, undergoing explosive rupture during phagocytosis, and relatively radiosensitive in the isolated state. The possibility that these properties might be related to membrane sulfhydryl groups was investigated by standard the binding of 203Hg‐labelled HgCL2 and p‐chloromercuribenzenesulfonate to granules isolated from rabbit peritoneal‐exudate neutrophils.Leucocyte lysosomes had a maximum mercury‐binding capacity of 1·92×10−7moles/mg. protein (7·5 × 10−17 moles per “average” granule), p‐chloro‐mercuribenzenesulfonate binding at 6·6 × 10−4 M was similar to this figure, but at lower concentrations binding of the mercurial was approx. 25% less than that of mercury. Binding of p‐chloromercurihenzenesulfonate was influenced by the physical state of the preparations as well as by the ionic composition of the suspending medium.Isolated granules were highly sensitive to mercury and p‐chloromencuribenzenesulfonate, undergoing rapid disruption upon incubation at 28° in the presence of low concentrations of these agents. At high concentrations of mercury (but not of p‐chloromercuribenzeuesulfonate) the granules became increasingly resistant to rupture. Lysosomes were more sensitive to gammaradiation when they were irradiated in the presence of 10 −5 M HgCl2, indicating that sulfhydryl groups may be involved in the rupture of the granules by radiation.