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Biomedical subjects

L Murray

Publications and source records attributed to L Murray.

At least 127 records · Page 7Linked to original sources
PubMed1989

Glucose-6-phosphate dehydrogenase. Characteristics revealed by the rat liver enzyme structure.

The primary structure of glucose-6-phosphate dehydrogenase from rat liver has been determined, showing the mature polypeptide to consist of 513 amino acid residues, with an acyl-blocked N-terminus. This structure is homologous to those of both other eutherian and marsupial mammals (human and opossum), thus characterizing a mammalian type enzyme to which the human form, notwithstanding its large number of genetic variants, conforms. The mammalian type differs from the fruit fly enzyme by about 50%. Known mutant forms exhibit further differences, widely distributed along the polypeptide chain. Structural patterns show glucose-6-phosphate dehydrogenases to consist of a few variable regions intermixed with relatively constant segments.

Amino Acid Sequence↗
PubMed1989

Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial.

Infection with the hepatitis C virus may result in chronic liver disease for which no effective therapy is now available. We studied the effects of recombinant human interferon alfa in a prospective, randomized, double-blind, placebo-controlled trial in patients with well-documented chronic hepatitis C. Forty-one patients were enrolled in the trial, 37 of whom were later found to have antibody to hepatitis C virus. Twenty-one patients received interferon alfa (2 million units) subcutaneously three times weekly for six months, and 20 received placebo. The mean serum aminotransferase levels and the histologic features of the liver improved significantly in the patients treated with interferon but not in the patients given placebo. Ten patients treated with interferon (48 percent) had a complete response, defined as a decline in mean serum aminotransferase levels to the normal range during therapy; three others had a decrease in mean aminotransferase levels of more than 50 percent. After treatment ended, however, serum aminotransferases usually returned to pretreatment levels; 6 to 12 months after the discontinuation of interferon therapy, only two patients (10 percent) still had normal values. We conclude that interferon alfa therapy is beneficial in reducing disease activity in chronic hepatitis C; however, the beneficial responses are often transient.

Adult↗
PubMed1989

The abnormal T lymphocytes in lpr mice transcribe interferon-gamma and tumor necrosis factor-alpha genes spontaneously in vivo.

The autoimmune mouse strain MRL/MPJ/lpr/lpr is characterized by accumulation of an abnormal T cell population which does not express CD4 or CD8 surface antigens. These cells were thought to be immunologically inert based on their inability to proliferate in response to a variety of T cell mitogens. We investigated the capacity of these cells to express lymphokine genes using a sensitive RNase protection assay. RNA was isolated from abnormal T cells which were purified directly from diseased animals, either as CD4-/CD8- or as fluorescence-activated cell sorter-isolated B220+/Thy-1+ cells. These RNA preparations contained no detectable interleukin (IL) 2, IL 4, IL 5 or IL 6 transcripts, but did contain transcripts of genes for interferon-gamma and tumor necrosis factor-alpha. Thus, this expanded population of abnormal cells spontaneously expresses these two lymphokines which have many interacting effects on the immune system, and may have important roles in the pathogenesis of autoimmune disease in lpr mice.

Animals↗
PubMed1989

Glucopenia-mediated release of somatostatin from incubated rat hypothalamus: monosaccharide specificity and role of glycolytic intermediates.

Rat hypothalamic somatostatin (SRIF) release in vitro is inversely related to medium glucose concentration and is stimulated by agents interfering with neural glucose uptake or metabolism. The present studies examined monosaccharide specificity of this effect by comparing the ability of glucose and nonmetabolized sugars (ribose, fructose, and galactose) to reverse glucopenia-mediated SRIF release. Removal of glucose from incubation medium resulted in a 7-fold stimulation of hypothalamic SRIF release (24.9 +/- 3.0 to 169.0 +/- 46.2 pg/5 min) that was promptly and fully reversed by readdition of glucose (21.5 +/- 6.0 pg/5 min). Depolarizing concentrations of potassium (40 mM) added to medium after incubation in the presence or absence of glucose produced similar 4-fold biphasic stimulation of SRIF release, suggesting that tissue viability was unimpaired by short term glucopenia. By contrast, nonmetabolized sugars (ribose, fructose, or galactose) at concentrations up to 28 mM were unable to reverse glucopenia-mediated hypothalamic SRIF release. These findings suggest that neural metabolism of glucose specifically influences hypothalamic SRIF release, an effect likely to depend on glycolysis with resulting energy production. This explanation is supported by the finding that the glycolytic intermediates dihydroxyacetone and glyceraldehyde were partly, and pyruvate completely, able to restore glucopenia-mediated SRIF release toward basal, with a maximal effect at 14 mM. Our present studies suggest that rat hypothalamic SRIF release reflects ambient glucose status, is stimulated by glucopenia, and may explain inhibition of GH secretion in the rat during hypoglycemia.

Animals↗
PubMed1989

Effects of tail docking and castration on behaviour and plasma cortisol concentrations in young lambs.

Behavioural and cortisol responses of lambs to the usual husbandry practices of castration and, or, tail docking using tight rubber rings were investigated between birth and seven days old. There were four treatments: control handling and blood sampling (n = 52), tail-docking (T) (n = 57), castration plus tail-docking (CT) (n = 54) and intravenous adrenocorticotrophin injection (ACTH) (n = 52). After treatment there was a transient rise in plasma cortisol concentration, the magnitude and duration of which increased in the following order; control, T, CT and ACTH. Behavioural characteristics indicative of distress included restlessness (standing up and lying down frequently, rolling, kicking, stamping), lateral recumbency, immobility with neck extension and hyperventilation. Using changes in cortisol concentrations and behaviour the lamb responses were characterised as reflecting 'mild disturbance without distress' (control, ACTH), 'mild distress' (T) and 'marked distress' (CT). The mild distress lasted for about 30 minutes in T lambs and marked distress for about 60 minutes in CT lambs.

Adrenocorticotropic Hormone↗
PubMed1989

Changes in the cortisol responses of lambs to tail docking, castration and ACTH injection during the first seven days after birth.

Cortisol responses of Dorset and Scottish Blackface lambs were investigated at six ages between birth and seven days. There were four treatments: control handling and blood sampling (n = 52), tail docking (T) (n = 57), castration plus tail docking (CT) (n = 54), and intravenous adrenocorticotrophin (ACTH) injection (n = 60). Most lambs exhibited transient rises in plasma cortisol concentrations after treatment and the results in individuals were expressed as the area under the cortisol curve (integrated response). Postnatal changes in the integrated responses of control, T and CT lambs differed significantly between the two breeds; in Dorsets they increased markedly between four hours and one day and then decreased, whereas in Scottish Blackface lambs there were no significant changes. The cortisol responses of ACTH lambs decreased markedly between four hours and seven days in both breeds. The results shed light on postnatal changes in the activity of the hypothalamic-pituitary-adrenal axis and suggest for both breeds that the average increments in ACTH secretion caused by noxious stimuli increased markedly during the first one to three days after birth. Whether this reflected parallel increases in the levels of distress experienced by the lambs remains to be clarified.

Adrenocorticotropic Hormone↗
PubMed1989

Primary peritonitis. An unusual operative diagnosis.

Primary peritonitis, or spontaneous bacterial peritonitis, is a highly morbid and often fatal complication of cirrhosis and other conditions associated with ascites. Prompt antibiotic therapy may be lifesaving, as may early surgical intervention in patients who have signs and symptoms of an acute abdomen. During a 5-year period, 12 patients had 14 episodes of primary peritonitis diagnosed in our hospital. Three patients had exploratory laparotomy, and gram-positive organisms were obtained from peritoneal fluid in two patients. The clinical features, patho-physiology, and natural courses of these patients are presented and the current literature reviewed.

Adult↗
PubMed1988

MESA is a Plasmodium falciparum phosphoprotein associated with the erythrocyte membrane skeleton.

The mature-parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum is an antigenically variable, high molecular weight protein of trophozoites and schizonts that is located at the erythrocyte surface membrane. It is first synthesized at the late ring stage and continues to be synthesized until late schizogony. MESA cannot be detected on the external surface of erythrocytes infected by trophozoites and early schizonts but is located at the internal surface in association with the erythrocyte membrane skeleton. The degree of association with the membrane skeleton varies among parasite lines, being greater in knobby parasite lines. MESA is phosphorylated and is present in a similar location to another phosphoprotein, the ring-infected erythrocyte surface antigen (RESA). However, it differs from RESA in being detected at a later stage of asexual development of the parasite.

Animals↗
PubMed1988

Late Niemann-Pick disease with neurovisceral storage: a classification problem.

A 51 year old man presented in 1969 with slowly progressive cerebellar ataxia of unknown origin. He was admitted to hospital aged 68 after a fall, and a ruptured spleen was removed at laparotomy. Histological analysis of the spleen suggested Niemann-Pick disease, which was subsequently confirmed. He deteriorated and died of bronchopneumonia shortly afterwards: subdural haemorrhage with storage material in neurones was found at necropsy. This late onset case of Niemann-Pick disease with neurovisceral storage is unusual and may represent a variant.

Age Factors↗
PubMed1988

Kniest dysplasia is characterized by an apparent abnormal processing of the C-propeptide of type II cartilage collagen resulting in imperfect fibril assembly.

Epiphyseal and growth plate cartilages from four cases of Kniest dysplasia have been studied. In each case collagen fibril organization appeared abnormal by electron microscopy compared with age-matched normal cartilages: fibrils were much thinner, of irregular shape and did not exhibit the characteristic banding pattern. This was associated with the absence (compared with normal cartilage) of the C-propeptide of type II collagen (chondrocalcin) from the extracellular matrix of epiphyseal cartilages, although it was detected (as in normal cartilages) in the lower hypertrophic zone of the growth plate in association with calcifying cartilage. The C-propeptide was abnormally concentrated in intracellular vacuolar sites in Kniest cartilages and its total content was reduced in all cases but not in all cartilages. Moreover, it was not a part of the procollagen molecule. In contrast, type II collagen alpha-chain size was normal, indicating the formation of a triple helix. Also type II collagen content was normal and it was present in extracellular sites and only occasionally detected intracellularly. These observations suggest that the defect in Kniest dysplasia may result from the secretion of type II procollagen lacking the C-propeptide and abnormal fibril formation, and that the C-propeptide is normally required for fibril formation.

Calcium-Binding Proteins↗
PubMed1987

Response of thyrotropin-secreting pituitary adenomas to a long-acting somatostatin analogue.

Thyrotropin-secreting pituitary adenomas are aggressive, invasive tumors that respond poorly to available surgical and medical treatments. Inappropriate release of thyrotropin by these tumors can result in hyperthyroidism. We treated five patients who had thyrotropin-secreting pituitary adenomas with the long-acting somatostatin analogue SMS 201-995, which was administered by subcutaneous injection in doses of 50 to 100 micrograms every 8 to 12 hours. Serum levels of thyrotropin were dramatically reduced by treatment in four of the five patients, and levels of another tumor marker, the alpha-subunit of thyrotropin, were reduced in all five. In two patients with hyperthyroidism due to production of excess thyrotropin by the tumor, treatment with the somatostatin analogue resulted in a sustained euthyroid state. One patient who was treated for more than 16 months had a persistent reduction in serum levels of thyrotropin and iodothyronines. We conclude that SMS 201-995 is an effective means of controlling hypersecretion of thyrotropin and the associated hyperthyroidism due to thyrotropin-secreting pituitary tumors.

Adenoma↗
PubMed1987

Effects on the murine mononuclear phagocyte system of chronic administration of liposomes containing cytotoxic drug or lipid A compared with empty liposomes.

In experiments designed to examine the adverse effects of chronic liposome administration in vivo on the mononuclear phagocyte system (reticuloendothelial system), the presence of drug entrapped in the liposomes may increase the level of reticuloendothelial impairment. We have compared the effects on the mononuclear phagocyte system in mice of chronic administration of empty liposomes with the effects of liposomes containing the anti-leishmanial drug meglumine antimoniate. We have also examined the effect on the mononuclear phagocyte system of continued injections of liposomes containing lipid A, a component of bacterial lipopolysaccharide, which is responsible for macrophage activation. Ten intravenous injections of multilamellar liposomes composed of dipalmitoylphosphatidylcholine and cholesterol (1:0.75 M ratio) were given to ICR mice over a 25-day period. Two individual groups of mice received endotoxin-free liposomes in which meglumine antimoniate was either present or absent. One addition group received liposomes containing lipid A derived from Escherichia coli lipopolysaccharide. A control group received sterile saline injections. In each group, a depression of the phagocytic index, as measured by reduction of uptake of particulate carbon, was observed among some of the individual animals 24 h after the first injection. In many mice a marked splenomegaly was observed. A depressed phagocytic index and splenomegaly were most marked for mice receiving lipid A liposomes. However, there was a large individual variability among mice receiving these preparations and some mice in each group had normal spleen size and a nearly normal phagocytic index. Tissue distribution of liposomes containing [14C]dipalmitoylphosphatidylcholine as a phospholipid marker was examined in all groups in mice 24 h after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Making the most of colostrum at lambing.

Lambs require between 180 and 210 ml colostrum/kg bodyweight during the first 18 hours after birth in order to provide sufficient fuel for heat production. Colostrum intakes of this order would usually provide enough immunoglobulins for protection against infections. Ewes which are well fed during late pregnancy produce more colostrum than their lambs need, those with singletons having enough for a second lamb, but in most underfed ewes the lamb's requirements for colostrum exceed the ewe's production. Colostrum can be readily obtained and stored for subsequent use. The yields are increased markedly when hand milking is preceded by an oxytocin injection, the intravenous dose being 5 iu and the suggested intramuscular dose being 10 to 15 iu. There is little practical benefit in milking ewes more than three times during the first 18 hours after birth.

Animals↗