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Biomedical subjects

N Harris

Publications and source records attributed to N Harris.

At least 73 records · Page 4Linked to original sources
PubMed1996

The effects of arginine administration on the levels of arginine, other amino acids and related amino compounds in the plasma, heart, aorta, vena cava, bronchi and pancreas of the rat.

Arginine (0.8g/kg, ip) or a vehicle was administered to rats and the levels of arginine and a large number of related amino compounds++ were measured in plasma, heart, aorta, vena cava, pancreas and bronchi at specified time intervals. Arginine levels (nmol/ml) increased in the plasma from 237 to 3172 at 15 min, 1236 at 30 min and 509 at 120 min. Peak concentrations (nmol/g) of arginine are reached in the tissues at 15 or 30 minutes with control and postinjection values of 500 and 1769 in the heart, 314 and 1563 in the aorta, 575 and 2976 in the vena cava, 760 and 1943 in the bronchi, and 234 and 3638 in the pancreas. Arginine injection also affects a number of amino acids and related compounds in the plasma and tissues most notably ornithine, isoleucine, phosphoserine, leucine and ethanolamine. However, plasma level changes do not predict tissue level changes which are highly specific for an individual compound and tissue. There was no general indication that arginine injection stimulates nitric oxide (NO) formation in any tissue. Thus, arginine is rapidly absorbed from the abdominal cavity into the blood stream, is quickly taken up by the tissues studied and disappears after about 2 to 3 hours. The effects seen after arginine administration could be caused by arginine per se and/or changes in one or more of the related amino compounds but not by NO.

Amino Acids↗
PubMed1996

Effect of arginine administration on plasma and brain levels of arginine and various related amino compounds in the rat.

Arginine (ARG) was injected (0.8 g/kg, i.p.) into rats and levels of ARG were determined in plasma and four brain areas in the morning and afternoon. In control rats, brain values for ARG and some amino compounds are lower in the afternoon than in the morning. After ARG administration, ARG levels increase about 10-fold in the plasma and 2- to 3-fold in the brain areas. Brain ARG levels follow plasma levels. Elevated ARG levels affect a number of related amino compounds both in the plasma and all brain areas most notably ornithine, phosphoserine, glycine, GABA and ammonia. An increase of citrulline after ARG administration suggests the possibility of ARG-stimulated nitric oxide formation in the midbrain. Thus, ARG shows a daily rhythm in the plasma and brain and its administration increases ARG brain levels which seem to follow plasma levels. In addition, ARG alters a number of other amino compounds most notably GABA, glycine, ornithine and ammonia, indicating that some pharmacological effects seen after ARG administration might be caused by elevated levels of ARG and/or changes in other amino compounds.

Amino Acids↗
PubMed1996

Three routine methods for measuring high-density lipoprotein cholesterol compared with the Reference Method.

We compared the performance of three methods for quantifying high-density lipoprotein cholesterol (HDL-C) with the Reference Method for HDL-C, using samples with a wide range of triglyceride (TG) concentrations (290-18000 mg/L). All three comparison assays-- utilizing a magnetic dextran sulfate precipitating reagent, a direct method, and a standard MgCl2-dextran sulfate reagent--were precise, with a run-to-run CV of less than or equal to 4.1%. However, the systematic error of these assays exceeded the National Cholesterol Education Program (NCEP) performance goal of less than or equal to 10% in half of the concentration ranges tested. Nevertheless, the total error of the assays generally meets the current 22% limit set by the NCEP. Although both the magnetic dextran sulfate precipitation reagent and the direct assay can be performed more rapidly than the MgCl2-dextran sulfate assay, the direct assay involves no sample preparation and requires only 4 microL of sample excluding the dead space. Although precipitation is frequently inadequate with the MgCl2-dextran sulfate reagent at TG concentrations >6000 mg/L, both the magnetic and the direct reagent show no interference from high TG concentrations as great as 18 000 mg/L.

Chemical Precipitation↗
PubMed1996

Analytical performance and clinical utility of a direct LDL-cholesterol assay in a hyperlipidemic pediatric population.

This study compares a new latex immunoseparation method for the direct determination of plasma low-density lipoprotein cholesterol (LDL-C) with the reference procedure for LDL-C (beta-quantification) in a pediatric hyperlipidemic population. The direct LDL-C assay has a mean bias of -98 mg/L in a fasting group (n = 96) of patients (mean triglycerides 1057 +/- 720 mg/L) and a bias of +177 mg/L in a nonfasting group (n = 42, mean triglycerides 4854 +/- 5457 mg/L). The mean total analytical error calculated from our data is 13.8%. The direct LDL-C assay and the commonly used Friedewald calculation respectively classified 81% and 84% of fasting patients correctly, according to the cutoffs of 1100 and 1300 mg/L for LDL-C set by the National Cholesterol Education Program for pediatric patients. Of combined fasting and nonfasting patients, 80% were correctly classified by the direct LDL-C assay. Therefore, despite several analytical shortcomings, the direct LDL-C assay may be useful in managing hyperlipidemic children without the need for a fasting specimen.

Adolescent↗
PubMed1996

Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement. A randomised controlled trial.

Seventy-eight patients having elective total hip replacement were randomised into 3 groups A) control; B) low molecular weight heparin: (enoxaparin 40 mg once daily) and C) enoxaparin (40 mg once daily) plus graduated elastic compression (TEDR stockings) for 8-12 days. All patients had a preoperative perfusion lung scan and chest X-Ray and a postoperative perfusion/ventilation scan together with bilateral ascending venography on days 8-12. A blood sample was taken preoperatively, on the 1st, 3rd and 5th postoperative day and at the end of the study. The control group received placebo injections. The venograms and V/Q scans were reported blindly by an independent panel of three and one radiologists respectively. An independent panel of assessors stopped entry in the control group when a total of 45 patients were admitted according to Ethics Committee directives. The study continued with groups B and C. The incidence of DVT (including isolated asymptomatic calf thrombi) was as follows: Group A (n = 14) 93%; Group B (n = 32) 38%; Group C (n = 32) 25% (chi 2; p < 0.001 for group A versus B or C). The incidence of proximal DVT was: Group A 57%; group B 28%; group C 13% (chi 2; p = 0.057 for group A versus B and p < 0.005 for group A versus C). The incidence of silent pulmonary embolism (PE) (new defect on V/Q scan) was 28% (8 out of 29) in patients with and 5% (2 out of 43) in patients without DVT (chi 2; p < 0.02). The combination of high TAT and low anti-Xa activity on the 1st postoperative day identified a high risk group of patients who had a 56% incidence of proximal DVT on the 8th to 12th postoperative day. Further studies are needed to confirm the suggested increased efficacy in prophylaxis by the combination of LMWH and GEC as compared with LMWH alone.

Aged↗
PubMed1996

Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

Adolescent↗
PubMed1995

Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites.

IFN-gamma-induced nitric oxide (NO) in the murine macrophage-derived cell line RAW 264.7 was previously shown to inhibit replication of the poxviruses ectromelia and vaccinia (VV) and HSV-1. In the current study we demonstrate that murine macrophages activated as a consequence of VV infection express inducible nitric oxide synthase. These activated macrophages were resistant to infection with VV and efficiently blocked the replication of VV and HSV-1 in infected bystander cells of epithelial and fibroblast origin. This inhibition was arginine dependent, correlated with nitrite production in cultures, and reversible by the NOS inhibitor N omega-monomethyl-L-arginine. NO-mediated inhibition of VV replication was studied by treatment of virus-infected human 293 cells with the NO donor S-nitroso-N-acetyl-penicillamine. Using a VV-specific DNA probe, antibodies specific for temporally expressed viral proteins, and transmission electron microscopy, we have shown that NO inhibited viral late gene protein synthesis, DNA replication, and virus particle formation, but not expression of the early proteins that were analyzed. Putative enzymatic targets of NO were identified by reversing the NO-mediated inhibition of VV replication in the 293 cells with exogenous ferrous sulfate and L-cysteine. Reversal of inhibition may derive from the capacity of these reagents to protect or regenerate nonheme iron or thiol groups, respectively, which are essential for the catalytic activities of enzymes susceptible to inactivation by NO.

Amino Acid Oxidoreductases↗
PubMed1995

Prolonged but partial impairment of the hypoglycaemic physiological response following short-term hypoglycaemia in normal subjects.

Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18-24 h after antecedent hypoglycaemia in both non-diabetic subjects and those with insulin-dependent diabetes mellitus. We examined these and peripheral physiological responses in eight non-diabetic subjects aged 23-35 years in the week following antecedent hypoglycaemia. Blood glucose levels were held at plateaus of 5 mmol/l and 2.5 mmol/l for 30 min during hyperinsulinaemic (60 mU x m-2x min-1) morning clamps on days 1, 3 and 8 of two study periods separated by at least 4 weeks. Measurements were made at time 0, 15 and 30 min of each plateau on each day. One the afternoon of Day 1 we also induced either euglycaemia with a blood glucose level of 5 mmol/l (control week) or hypoglycaemia of 2.9 mmol/l (hypo week) for 2 h in random order. The adrenaline response to morning hypoglycaemia (p<0.001 on all days) was attenuated on Day 3 (p<0.05) and Day 8 (p<0.05) compared to Day 1 of hypo week only. Sweating was also attenuated on Day 3 (p<0.05) and Day 8 (p<0.02) of hypo week only. Noradrenaline levels and tremor increased during hypoglycaemia on each study day (p<0.05) but did not differ between days in either week. During hypo week only, the total symptom score response to hypoglycaemia was attenuated on Day 3 (p<0.03) but not Day 8 (p=0.10). Autonomic symptoms were similarly affected. In summary, the physiological responses to hypoglycaemia are affected differentially by antecedent hypoglycaemia with sweating and adrenaline responses remaining impaired for at least adrenaline responses remaining impaired for at least 5 days.

Adult↗
PubMed1995

Effect of stress on amino acids and related compounds in various tissues of the rat.

The composition of various amino acids and related compounds in the aorta, ventricle, atria, liver, kidney, pancreas, bronchi and adrenals of rats is presented. These patterns are qualitatively similar, but quantitatively different. Stress changed these patterns. In the aorta, alpha-aminobutyric acid and ammonia are decreased. In the ventricle, phosphoserine and red. Glutathione are increased; and ammonia, arginine, asparagine, carnosine, ethanolamine, glutamic acid, glutamine, lysine, phosphoethanolamine and taurine are decreased. In the atria, alpha-aminobutyric acid, aspartic acid, ethanolamine and red. glutathione are increased; and ammonia is decreased. In the liver, alpha-aminobutyric acid, cystine, isoleucine, red. glutathione, methionine and phenylalanine are increased. In the kidney, ethanolamine is increased; and beta - aminobutyric acid, citrulline, cystathionine, glutamic acid, glycine and tryptophan are decreased. In the pancreas, alpha-aminoadipic acid, ox. glutathione, leucine, glutamine, 1-methylhistidine, phenylalanine, phosphoserine, tryptophan and valine are increased; and ammonia, cystine and aspartic acid are decreased. In the adrenal glands, anserine, glutamic acid, glutamine and ox. glutathione are increased; and arginine is decreased. In the bronchi, ethanolamine and beta-alanine are increased and alpha-aminobutyric acid and ox. glutathione are decreased. Thus, stress affects certain amino compounds but changes are substance and tissue specific and independent of changes seen in the plasma.

Amino Acids↗
PubMed1995

Navigator: tools for informal structure-activity relationship discovery.

Navigator is a molecular database visualization system, designed to support exploratory data analysis and informal structure-activity relationship studies. In addition to the operations commonly found in chemical database systems, it provides new tools that facilitate substituent analysis and help elucidate the relationships among similar molecules and between related assays. Navigator's capabilities include two ways of displaying the relationships between analogs, mouse-sensitive charts of sets of molecules, mouse-sensitive plots of assay relationships, and access to a system for three-dimensional quantitative structure-activity relationship discovery. Navigator's mouse-based user interface provides a one-object/one-window paradigm that makes data manipulation easy even for inexperienced users. Navigator runs on Silicon Graphics workstations.

Computer Graphics↗
PubMed1995

V/Q defects and deep venous thrombosis following total hip replacement.

Seventy-two patients undergoing elective total hip replacement were studied with bilateral venography, pre-operative and post-operative lung scans. Twelve belonged to a control group that received placebo injections and 60 patients to treatment groups that received low molecular weight heparin. The incidence of deep venous thrombosis was 11 (92%) of 12 patients in the control group and 18 (30%) of 60 patients in the treatment group (X2: P < 0.001). The incidence of pulmonary embolism (new unmatched perfusion defects) was five (42%) of the 12 patients in the control group and five (8.3%) of the 60 patients in the treatment groups (X2: P < 0.002). The incidence of pulmonary embolism (new unmatched perfusion defects) was eight (27.5%) of 29 patients with deep venous thrombosis and two (4.6%) of 43 without deep venous thrombosis (X2: P < 0.02). Of the ten patients who had pulmonary embolism according to this study's criteria (one or more new defect on perfusion, unmatched on the ventilation scan), eight would have been classified as high probability by the Biello criteria, and only five by the PIOPED criteria, if the pre-operative scans were not available. We conclude that having a pre-operative lung scan improves ability to interpret the postoperative lung scans in high risk patients.

Elective Surgical Procedures↗
PubMed1995

Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication.

Gamma interferon (IFN-gamma)-induced nitric oxide synthase (iNOS) and nitric oxide (NO) production in the murine macrophage-like RAW 264.7 cells were previously shown to inhibit the replication of the poxviruses vaccinia virus (VV) and ectromelia virus and herpes simplex virus type 1. In the current study, we performed biochemical analyses to determine the stage in the viral life cycle blocked by IFN-gamma-induced NO. Antibodies specific for temporally expressed viral proteins, a VV-specific DNA probe, and transmission electron microscopy were used to show that the cytokine-induced NO inhibited late protein synthesis, DNA replication, and virus particle formation but not expression of the early proteins analyzed. Essentially similar results were obtained with hydroxyurea and cytosine arabinoside, inhibitors of DNA replication. Enzymatically active iNOS was detected in the lysates of IFN-gamma-treated but not in untreated RAW 264.7 cells. The IFN-gamma-treated RAW 264.7 cells which express iNOS not only were resistant to productive infection but also efficiently blocked the replication of VV in infected bystander cells of epithelial origin. This inhibition was arginine dependent, correlated with nitric production in cultures, and was reversible by the NOS inhibitor N omega-monomethyl-L-arginine.

Amino Acid Oxidoreductases↗
PubMed1994

Evaluation of Epstein-Barr virus antibody patterns and detection of viral markers in the biopsies of patients with Hodgkin's disease.

We assessed the relationship of Epstein-Barr virus (EBV) serology to the presence or absence of EBV genome in 39 cases of Hodgkin's disease (HD). Biopsies from patients included in 2 previous published studies, 1 involving patients from the United States (eastern Massachusetts) and 1 from Denmark, were evaluated for EBV (EBER-1) and latent membrane protein (LMP-1). The presence of EBV in Reed-Sternberg cells in the biopsies correlated with the histologic subtype of HD (mixed cellularity and lymphocyte depletion) but not with IgG antibody titers against the viral capsid antigen (VCA). These data suggest that, unlike Burkitt's lymphoma, the IgG antibody against VCA is not predictive of the presence or absence of EBV in Reed-Sternberg cells in HD. The predictive value of other antibodies should be evaluated.

Adult↗
PubMed1994

Purification and identification of a vaccinia virus-encoded intermediate stage promoter-specific transcription factor that has homology to eukaryotic transcription factor SII (TFIIS) and an additional role as a viral RNA polymerase subunit.

Enzymes and factors, required for in vitro transcription of templates regulated by vaccinia virus intermediate stage promoters, are present in HeLa cells infected with vaccinia virus in the presence of an inhibitor of DNA replication. Previous studies indicated that in vitro transcription could be reconstituted by adding a partially purified transcription factor to the viral RNA polymerase and capping enzyme. By using an independent purification procedure, we isolated two vaccinia virus intermediate were necessary for transcription of several different intermediate stage promoter templates but not for early or late stage promoter templates. VITF-1 was purified to homogeneity, and the sequences of two tryptic peptides were mapped to the fourth open reading frame within the HindIII E fragment (E4L) of the vaccinia virus genome, which had previously been shown to encode an RNA polymerase subunit of 30 kDa (RPO30) with homology to eukaryotic transcription elongation factor SII. Co-chromatography of VITF-1 with the E4L-derived protein was demonstrated using specific antiserum. In addition, transcriptionally active recombinant VITF-1 was made by expressing the E4L open reading frame in Escherichia coli. Thus, E4L encodes a multifunctional protein, serving as a RNA polymerase subunit and a stage-specific transcription factor. The stepwise binding of capping enzyme, VITF-1, and VITF-2 to a DNA/viral RNA polymerase complex was demonstrated.

Amino Acid Sequence↗
PubMed1994

The exon-intron structure and chromosomal localization of the mouse macrophage mannose receptor gene Mrc1: identification of a Ricin-like domain at the N-terminus of the receptor.

The macrophage mannose receptor is a transmembrane protein that is expressed on the surface of mature macrophages. The ectodomain of the receptor contains multiple domains, eight of which belong to the calcium-dependent C-type lectin family. The mannose receptor binds to carbohydrate polymers that have a high content of mannose. This property allows this protein to function as a phagocytic receptor that participates in first-line host defense against invading microorganisms. In this paper we describe the intron-exon structure of the mouse macrophage mannose receptor gene which was found to span at least 70 kilobases. We also report the localization of this gene, termed Mrc1, to mouse Chromosome 2. Like its human counterpart, Mrc1 contains 30 exons and 29 introns. A protein module that resembles a subdomain of the B chain of the plant lectin Ricin has been found within the N-terminal cysteine-rich domain of the mannose receptor.

3T3 Cells↗
PubMed1994

Isolation of a mRNA encoding a nucleoside diphosphate kinase from tomato that is up-regulated by wounding.

A cDNA clone (TAB2) encoding a nucleoside diphosphate (NDP) kinase has been isolated from a tomato (Lycopersicon esculentum Mill. cv. Ailsa Craig) cDNA library. The clone is 590 bp long and exhibits a high degree of sequence identity with spinach NDP kinases I and II, Pisum sativum NDP kinase I, Arabidopsis thaliana NDP kinase, Drosophila melanogaster NDP kinase, Dictyostelium discoideum NDP kinase and human Nm 23-H1 and Nm23-H2. Northern analysis has revealed that the mRNA encoded by TAB2 is up-regulated in both leaf and stem tissue in response to wounding. The increase is apparent within 1 h of wounding and is not further elevated by application of ethylene. Southern blot analysis indicates that TAB2 is a member of a small gene family.

Amino Acid Sequence↗