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Biomedical subjects

T J Harris

Publications and source records attributed to T J Harris.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of prolonged catecholamine infusion on immunoregulatory function: implications in congestive heart failure.

OBJECTIVES: This study sought to characterize the effects of prolonged catecholamine infusion on immunoregulatory cell traffic and activation. BACKGROUND: Immunoregulation has been shown to be partially controlled by the sympathetic nervous system. Although short-term elevation of catecholamine levels is known to alter immunoregulatory cell traffic and activation, the effects of prolonged heightened sympathetic nervous system activity have not adequately been studied. We believe that the alterations in immune function seen in patients with congestive heart failure are linked to a prolonged elevation of circulating catecholamine levels. METHODS: To characterize the effects of prolonged elevation of catecholamine levels, rats received 4 weeks of constant infusion of epinephrine or norepinephrine through implanted osmotic minipumps. Peripheral and splenic leukocyte subsets, T cell proliferation and interleukin-2 receptor expression were quantified. Antibody production to the novel antigen keyhole limpet hemocyanin was assessed over the 4-week treatment period. RESULTS: Both epinephrine and norepinephrine caused significant splenic atrophy and cardiac hypertrophy; both were blocked by propranolol. Epinephrine induced lymphocytosis; both catecholamines caused an increase in natural killer cells. In the spleen, both epinephrine and norepinephrine led to a dose-dependent decrease in total T cells, suppressor/cytotoxic T cells and natural killer cells and a significant increase in B cells. Epinephrine at the low dose enhanced mitogen-induced proliferation and interleukin-2 receptor expression. Norepinephrine at the low dose appeared to diminish proliferation. Epinephrine tended to inhibit IgG antibody production, whereas norepinephrine had no effect. CONCLUSIONS: The results of our study indicate that prolonged elevation of catecholamine levels alters immune cell proliferation and differentiation. These alterations differ greatly from those induced by short-term stimulation but, for the most part, parallel those found in patients with congestive heart failure. We postulate that the shifts in immunoregulatory cell type and function seen in patients with congestive heart failure are due, in part, to longstanding increases in circulating catecholamine levels and may play an important role in the pathogenesis and progression of disease.

Animals↗
PubMed1995

Effects of enalapril on T and B cell function in rats after myocardial infarction.

The cellular mechanisms following myocardial infarction remain poorly characterized. It is believed that an inflammatory and immunologic process may be involved and that the beneficial effects of enalapril on remodeling may, in part, work through an immune mechanism. To characterize the effect of enalapril on immune alterations in the late phase of ventricular remodeling after myocardial infarction, rats underwent left coronary artery ligation followed by 6 weeks of either enalapril or placebo treatment. Infarct sizes, heart weights, and volumes were compared. Peripheral and splenic leukocyte and lymphocyte subsets, along with T cell blastogenesis, were quantified in enalapril treated rats 6 weeks after coronary ligation and compared to untreated control rats. Additionally, antibody production to a de novo antigen, keyhole limpet hemocyanin, was assessed with and without treatment. Average infarct size was equivalent among enalapril-treated myocardial infarction rats and untreated infarct rats. There was, however, less left and right ventricular hypertrophy in the enalapril treated group. Enalapril completely prevented the 42% increase in white blood count, the 88% increase in neutrophils, and the 28% increase in lymphocyte count seen in untreated infarct rats. Both untreated and enalapril treated rats tended toward a decrease in T helper:suppressor ratio. All rats treated with enalapril, however, had a significant increase in the T helper:suppressor ratio versus untreated control rats (F = 3.6, P = .018). Blastogenesis was markedly increased in T cells from infarcted animals. This was mitigated by treatment with enalapril. Additionally, immunoglobulin G antibody production was significantly lessened in rats treated with enalapril. The results of this study suggest that alterations in immunoregulatory cell type and function occurs following myocardial infarction. The beneficial effects of the angiotensin-converting enzyme inhibitor enalapril may be, in part, due to its mitigating effects on immune cell release and activation following myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Mathematical modelling of immobilized animal cell growth.

A two-dimensional mathematical model for animal cell growth was employed to study the suspension, as well as stationary, culture of micro-encapsulated and gel immobilized animal cells. For stationary microcapsules with low-viscosity intracapsular liquid, it was found that capsule radius, capsule loading and medium-change time have the most significant effects on the intracapsular cell density. The model was also adapted to simulate other scenarios of cell growth such as in gel beads and suspended microcapsules. The simulated time course of oxygen concentration and specific growth rate revealed a complicated interaction between material transport and cell growth kinetics. With the mass transfer coefficient for oxygen transfer (KLa') into the medium equal to 4.0 hr-1, for instance, it was found that the specific growth rate of the microencapsulated cells was controlled by the supply of glucose and oxygen. When the value of KLa' was reduced to 0.6 hr-1, however, oxygen supply appeared to be the sole factor affecting the specific growth rate. In the case of suspended gel beads, a simulation revealed a higher cell density towards the gel bead surface. The transport of nutrients and oxygen to the central region of the gel bead was apparently blocked by the surrounding cells.

Animals↗
PubMed1994

Exercise-induced enhancement of immune function in the rat.

BACKGROUND: There have been many anecdotal reports that regular, moderate exercise confers some protective immunity against infection. There has been little scientific evidence to support this. It is also unclear whether training alters lymphocyte trafficking from the spleen to the periphery after a bout of exhaustive exercise. METHODS AND RESULTS: To determine the effect of moderate training on in vivo antibody production, using rats as an animal model, we gradually trained 18 rats using a swimming protocol for a 4-week period after injection and booster with Keyhole limpet hemocyanin antigen. There were 9 age-matched controls. At the conclusion of training, both groups underwent a short-term exhaustive swim. The trained group showed marked enhancement of IgM and IgG production. After short-term exercise, both groups had acute lymphocytosis, mainly T(suppressor)/cytolytic and natural killer cells with decreases in T(helper) (trained), B cells, and the Th-to-Ts ratio. The changes in the splenocyte subsets were the opposite of the changes in the peripheral blood. With respect to function, after exhaustive exercise, there was a slight increase in mitogenesis and interleukin-2 receptor expression to concanavalin A (untrained more than trained) compared with controls. CONCLUSIONS: Regular, moderate training enhances antibody production to specific de novo antigen both early and late. In addition, short-term exercise leads to selective release of immune cells from the spleen and results in slightly enhanced function of splenocytes. Direct stimulation by the sympathetic nervous system and catecholamines is the proposed mechanism for the changes seen after short-term exercise and possibly antibody production during training.

Animals↗
PubMed1993

Activity of morantel citrate against strains of benzimidazole-resistant nematodes of sheep in the United Kingdom.

The activity of morantel citrate (5.94 mg/kg base) was determined in laboratory tests against field isolates of benzimidazole-resistant nematodes. Its efficacies against adult and seven-day-old worms were 100 per cent and 100 per cent for Cooperia curticei, 95.1 per cent and 69.8 per cent for Haemonchus contortus and 100 per cent and 82 per cent for Ostertagia circumcincta. Morantel citrate was 100 per cent effective against benzimidazole-susceptible Nematodirus battus and Trichostrongylus vitrinus, and it reduced faecal egg counts by 97.9 per cent in sheep infected naturally with benzimidazole-resistant H contortus and O circumcincta.

Animals↗
PubMed1993

Immune function in patients with chronic stable congestive heart failure.

The objective of this study was to ascertain whether immune abnormalities were present in a group of patients with chronic stable heart failure at a time when sympathetic drive was not excessive. Elevated sympathetic tone not only plays an important role in the pathophysiologic characteristics of congestive heart failure but may also regulate certain aspects of immune function, which has been shown to be abnormal in patients with severe heart failure. Studies have indicated a high incidence of heterophil antibodies against constituents of the heart, the presence of antibody-mediated cytotoxicity against cultured heart cells, and a decrease in suppressor and natural killer-cell function in patients with idiopathic dilated cardiomyopathy. Lymphocytes were separated over a Ficoll-Hypaque gradient. Lymphocyte subtypes and well as interleukin-2 receptors were detected by means of mouse monoclonal antibodies conjugated with fluorescein or phycoerytherin, and immunofluorescence was measured with a flow cytometer. Mitogen proliferation was assessed by tritiated thymidine incorporation in the presence of either conconavalin A or tetanus toxoid. Serum was used in conjunction with iodine 125-labeled iodopindolol binding to rat cardiac membranes to attempt to detect beta-receptor antibodies. In patients with ischemic (n = 21) and idiopathic (n = 16) cardiomyopathy, the norepinephrine levels were modestly elevated (idiopathic = 482 +/- 70 pg/ml; ischemic = 501 +/- 45 pg/ml) compared with control subjects without heart disease (n = 10; norepinephrine = 252 +/- 70 pg/ml). We found no differences in the number and subtypes of circulating lymphocytes in the three groups, and there was no serum inhibition of beta-binding to rat cardiac membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Persistent efficacy of doramectin against experimental nematode infections in calves.

Three studies were conducted involving cattle exposed to experimental nematode infections. These studies were designed to investigate the prophylactic activity of a single subcutaneous treatment of doramectin at 200 micrograms kg-1 body weight against infections of Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus. For each study, parasite-naive calves were randomly allocated to either a treated or a matched control group. One group received doramectin and the other received doramectin and the other received either no treatment or an injection of saline at 1 ml per 50 kg body weight by the subcutaneous route. Thereafter, all calves received a daily oral challenge of infective larvae of the particular parasite species on test in each study. Challenge of each pair of treatment/control groups continued for periods of 14, 21 or 28 days. An interval of 14-21 days was then allowed to permit the parasites which had established to mature, after which all animals were slaughtered and their worm burdens determined using standard techniques. Geometric mean worm burdens were calculated from the log worm counts and used to estimate percentage efficacy. Accumulated burdens of C. oncophora in doramectin-treated cattle resulting from a daily challenge infection for 14 or 21 days were reduced by 99.2% and 90.7% respectively, in comparison with those of non-treated control animals. For D. viviparus, burdens were reduced by 100% and 99.9% after a 21 or 28 day challenge, respectively. The corresponding figures for O. ostertagi were 99.9% after a 21 day challenge and 93.7% after a 28 day challenge.

Analysis of Variance↗
PubMed1993

Efficacy of doramectin in the prevention of gastrointestinal nematode infections in grazing cattle.

Two studies were performed to investigate the efficacy of doramectin in the prevention of infection with Ostertagia ostertagi and Cooperia oncophora in grazing calves. In each study, 24 parasite-naive calves were randomly allotted to two equal groups and treated with either doramectin at 200 micrograms kg-1 or saline prior to mid-season turnout (Day 0) onto contaminated pasture. Faecal egg counts were carried out twice weekly from 15 to 64 days after turnout and the cumulative faecal egg count was calculated for each group of calves. In the doramectin-treated animals, eggs first appeared in the faeces 19 days and 22 days later than in controls for Studies 1 and 2, respectively. Mean cumulative faecal egg counts over the 64 days were reduced in the doramectin-treated groups by 71% and 87% for Studies 1 and 2, respectively (P < 0.01). The potential utility of injectable doramectin in the seasonal control of gastrointestinal nematode infestations in relation to these findings is discussed.

Analysis of Variance↗
PubMed1992

Sequence data.

Explore the source record for details and available documents.

DNA↗
PubMed1990

Disulphide bond assignment in human tissue inhibitor of metalloproteinases (TIMP).

Disulphide bonds in human recombinant tissue inhibitor of metalloproteinases (TIMP) were assigned by resolving proteolytic digests of TIMP on reverse-phase h.p.l.c. and sequencing those peaks judged to contain disulphide bonds by virtue of a change in retention time on reduction. This procedure allowed the direct assignment of Cys-145-Cys-166 and the isolation of two other peptides containing two disulphide bonds each. Further peptide cleavage in conjunction with fast-atom-bombardment m.s. analysis permitted the assignments Cys-1-Cys-70, Cys-3-Cys-99, Cys-13-Cys-124 and Cys-127-Cys-174 from these peptides. The sixth bond Cys-132-Cys-137 was assigned by inference, as the native protein has no detectable free thiol groups.

Amino Acid Sequence↗
PubMed1989

Interaction between coccidia and Nematodirus battus in lambs on pasture.

Five thousand oocysts of each of two species of coccidia, Eimeria crandallis and E ovinoidalis or 30,000 infective larvae of Nematodirus battus, given as single infections to three- to five-week-old lambs, caused only transient diarrhoea and had no effect on growth. Lambs infected first with coccidia and two weeks later with N battus suffered severe diarrhoea, weight loss and some deaths. Simultaneous administration of the coccidia and the nematodes increased the clinical severity of the syndrome and increased the numbers of nematode eggs produced.

Animals↗
PubMed1988

A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite.

As a consequence of gene cloning and DNA sequencing several gene families are emerging in the field of cell-cell recognition. These include immunoglobulins, integrins, certain extracellular glycoproteins and a family of functionally unrelated proteins which include factor B. We report here the cloning and sequencing of a gene from Plasmodium falciparum, coding for a protein we call thrombospondin related anonymous protein (TRAP), which shares certain sequence motifs common to other well-characterized proteins. The most significant homology is based around the sequence Trp-Ser-Pro-Cys-Ser-Val-Thr-Cys-Gly (WSPCSVTCG), present in three copies in region I of thrombospondin (TSP), six copies in properdin (P) and one copy in all the circumsporozoite (CS) proteins sequenced so far. TRAP also shares with certain extracellular glycoproteins, including TSP, the cell-recognition signal Arg-Gly-Asp (RGD), which has been shown to be crucial in the interaction of several extracellular glycoproteins with members of the integrin superfamily. Unlike the CS protein, TRAP is expressed during the erythrocytic stage of the parasite life cycle.

Amino Acid Sequence↗
PubMed1988

The complete amino acid sequence of human complement factor H.

The complete amino acid sequence of the human complement system regulatory protein, factor H, has been derived from sequencing three overlapping cDNA clones. The sequence consists of 1213 amino acids arranged in 20 homologous units, each about 60 amino acids long, and an 18-residue leader sequence. The 60-amino-acid-long repetitive units are homologous with those found in a large number of other complement and non-complement proteins. Two basic C-terminal residues, deduced from the cDNA sequence, are absent from factor H isolated from outdated plasma. A tyrosine/histidine polymorphism was observed within the seventh homologous repeat unit of factor H. This is likely to represent a difference between the two major allelic variants of factor H. The nature of the cDNA clones indicates that there is likely to be an alternative splicing mechanism, resulting in the formation of at least two species of factor H mRNA.

Amino Acid Sequence↗
PubMed1988

Radiotherapy for superficial skin cancer at the Queensland Radium Institute: famine in the land of plenty.

Superficial skin cancer is the most common malignancy in man, and radiotherapy has played an important curative role since the early part of the 20th century. We present an overview of the changing pattern of care for patients with superficial skin cancer at the Queensland Radium Institute (QRI), Brisbane--the skin cancer "capital" of the world. Although some 90,000 clinically-diagnosed skin cancers have been treated by radiotherapy at the QRI during the period 1944-1985, we document a dramatic decline in radiotherapy usage for superficial skin cancers over the past 10-15 years. We identify and discuss the major reasons for this changing pattern of care: (a) policy changes initiated by radiation oncologists because of unsightly radiation scars caused by the Queensland climate, (b) improvements in the availability and technical aspects of surgery and dermatology, and (c) surgical preference.

Climate↗