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Biomedical subjects

H Henry

Publications and source records attributed to H Henry.

At least 19 recordsLinked to original sources
PubMed2006

Population pharmacokinetics of imatinib and the role of alpha-acid glycoprotein.

AIMS: The aims of this observational study were to assess the variability in imatinib pharmacokinetics and to explore the relationship between its disposition and various biological covariates, especially plasma alpha1-acid glycoprotein concentrations. METHODS: A population pharmacokinetic analysis was performed using NONMEM based on 321 plasma samples from 59 patients with either chronic myeloid leukaemia or gastrointestinal stromal tumours. The influence of covariates on oral clearance and volume of distribution was examined. Furthermore, the in vivo intracellular pharmacokinetics of imatinib was explored in five patients. RESULTS: A one-compartment model with first-order absorption appropriately described the data, giving a mean (+/-SEM) oral clearance of 14.3 l h-1 (+/-1.0) and a volume of distribution of 347 l (+/-62). Oral clearance was influenced by body weight, age, sex and disease diagnosis. A large proportion of the interindividual variability (36% of clearance and 63% of volume of distribution) remained unexplained by these demographic covariates. Plasma alpha1-acid glycoprotein concentrations had a marked influence on total imatinib concentrations. Moreover, we observed an intra/extracellular ratio of 8, suggesting substantial uptake of the drug into the target cells. CONCLUSION: Because of the high pharmacokinetic variability of imatinib and the reported relationships between its plasma concentration and efficacy and toxicity, the usefulness of therapeutic drug monitoring as an aid to optimizing therapy should be further investigated. Ideally, such an approach should take account of either circulating alpha1-acid glycoprotein concentrations or free imatinib concentrations.

Administration, Oral↗
PubMed2004

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI.

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4 +/- 0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k(ep) and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k(ep) decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.

Animals↗
PubMed2004

Detection of oligoclonal free kappa chains in the absence of oligoclonal IgG in the CSF of patients with suspected multiple sclerosis.

BACKGROUND: Oligoclonal free kappa bands are present as frequently as oligoclonal IgG bands in the cerebrospinal fluid (CSF) from patients with definite multiple sclerosis (MS) and can even occur in the absence of oligoclonal IgG. As such, they too are markers of an ongoing intrathecal immune process. OBJECTIVES: To determine how frequently oligoclonal free kappa bands are detectable in the CSF from patients with clinical signs and symptoms suggestive of MS in the absence of CSF restricted oligoclonal IgG. METHODS: An immunoaffinity mediated immunoblotting technique specific for free kappa chains was used, after isoelectric focusing of paired CSF and serum samples from 33 patients with clinical signs and symptoms suggestive of MS but without CSF oligoclonal IgG. CSF data were correlated with MRI results in the context of the new diagnostic criteria from McDonald et al. RESULTS: Eighteen CSF samples contained oligoclonal free kappa bands (54%), mainly from patients with motor dysfunction (83%) and optic neuritis (64%). All patients with a positive MRI according to Barkhof's criteria (n = 6) had free kappa bands in their CSF. CONCLUSIONS: (1) Oligoclonal free kappa bands in the CSF are related to the dissemination of MS lesions; (2) such bands should be looked for in oligoclonal IgG negative CSF, and (3) the presence of free kappa bands in the CSF may be a substitute for oligoclonal IgG in the McDonald's criteria for diagnosis of MS.

Adolescent↗
PubMed2001

Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study.

Creatine is synthesized from arginine by L-arginine:glycine amidinotransferase (AGAT) and S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT) and can be taken up by cells by creatine transporters (CRT). While creatine is mainly synthesized by the liver and the kidney, most of other tissues, including the brain, also express AGAT and GAMT. There is evidence that the permeability of the blood-brain barrier (BBB) for creatine is limited, suggesting that the brain is dependent on its own creatine synthesis. In order to better understand creatine synthesis and transport in the central nervous system (CNS), we studied the regional distribution of cells expressing AGAT, GAMT and the creatine transporter CRT1 in the adult rat brain by non-radioisotopic in situ hybridization. AGAT and GAMT presented an ubiquitous neuronal and glial expression, whereas CRT1 was present in neurons and oligodendrocytes throughout the brain, but not in astrocytes. This indicates that all cells in the CNS can synthesize creatine from arginine. The absence of expression of CRT1 in astrocytes and particularly in those contacting capillary endothelial cells (BBB) reinforces the idea that under normal conditions the creatine used by the brain is synthesized mainly in the CNS. Furthermore, the expression of CRT1 by neurons and oligodendrocytes indicates that creatine trafficking is possible in those brain areas of main creatine consumption.

Amidinotransferases↗
PubMed2001

Measurement characteristics of 2 different self-monitoring tools used in a dietary intervention study.

OBJECTIVE: To examine the measurement characteristics of 2 self-monitoring tools, a food diary and fat scan, used in the dietary intervention of the Women's Health Trial: Feasibility in Minority Populations study. DESIGN: Comparison of fat intake reported on the self-monitoring tools to a criterion measure of fat intake, specifically the mean of a food frequency questionnaire and a 4-day food record. The main outcome measures were differences in fat grams and correlations between each of the self-monitoring tools and the criterion measure. SUBJECTS/SETTING: Six-month postrandomization data from 313 women aged 50 to 79 years who participated in the intervention group of the Women's Health Trial: Feasibility in Minority Populations study. RESULTS: Both self-monitoring tools underestimated fat intake compared to the criterion measure, the food diary by 9 g and the fat scan by 6 g. The self-monitoring instruments were better than chance at detecting a low-fat dietary pattern, however, and did not differ from each other in their ability to do so. APPLICATIONS/CONCLUSIONS: The self-monitoring tools were modestly precise as measures of fat intake, but neither was sufficiently accurate to be reliable as a sole assessment of dietary adherence. Dietetics professionals are encouraged to assess the measurement properties of self-monitoring tools to use them appropriately in supporting dietary changes.

Aged↗
PubMed2000

Linear stability of scroll waves.

A full linear stability of a straight scroll wave in an excitable medium is presented. The five eigenmode branches which correspond to deformation in the third dimension of the five main modes of two-dimensional (2D) spiral dynamics are found to play a dominant role. For untwisted scroll waves, modulations in the third dimension have stabilizing or destabilizing effects on the different modes depending on the parameter regimes, in partial agreement with previous predictions. The influence of twist on the different branches is investigated. In particular, the sproing instability is seen to arise from the twist-induced deformation of the translation branches above a threshold twist.

Journal Article↗
PubMed2000

Amyloid and non-amyloid forms of 5q31-linked corneal dystrophy resulting from kerato-epithelin mutations at Arg-124 are associated with abnormal turnover of the protein.

Mutations in kerato-epithelin are responsible for a group of hereditary cornea-specific deposition diseases, 5q31-linked corneal dystrophies. These conditions are characterized by progressive accumulation of protein deposits of different ultrastructure. Herein, we studied the corneas with mutations at kerato-epithelin residue Arg-124 resulting in amyloid (R124C), non-amyloid (R124L), and a mixed pattern of deposition (R124H). We found that aggregated kerato-epithelin comprised all types of pathological deposits. Each mutation was associated with characteristic changes of protein turnover in corneal tissue. Amyloidogenesis in R124C corneas was accompanied by the accumulation of N-terminal kerato-epithelin fragments, whereby species of 44 kDa were the major constituents of amyloid fibrils. R124H corneas with prevailing non-amyloid inclusions showed accumulation of a new 66-kDa species altogether with the full-size 68-kDa form. Finally, in R124L cornea with non amyloid deposits, we found only the accumulation of the 68-kDa form. Two-dimensional gels revealed mutation-specific changes in the processing of the full-size protein in all affected corneas. It appears that substitutions at the same residue (Arg-124) result in cornea-specific deposition of kerato-epithelin via distinct aggregation pathways each involving altered turnover of the protein in corneal tissue.

Amyloid↗
PubMed1999

Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) alpha, interleukins (IL) 2, 4, 6, and 10, and IgG oligoclonal bands (IgG OB) in vitro production was assessed, after whole-blood stimulation with lipopolysaccharide or concanavalin A, in 61 patients presenting with relapsing-remitting, relapsing-progressive, or chronic progressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) beta 1 a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-beta 1 a increases TNF-alpha and decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1 a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-alpha, IL-2, IL-4, IL-6, and IL-10 in vitro production generally found no statistically significant correlations (partly explained by the limited number of values in the various groups), IL-6 was shown to drop during the periods surrounding relapse (P = 0.05) in the absence of treatment, while TNF-alpha (P = 0.04) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-alpha was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production of IL-10 detected before or at relapse with AZA and IFN-beta 1 a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results stress the difficulties in studying the state of stimulation of different populations of leukocytes by using a variety of in vitro stimuli and in establishing a correlation between mRNA studies and the amount of final or active protein produced.

Adjuvants, Immunologic↗
PubMed1999

IgE and T-cell responses to high-molecular weight allergens from bee venom.

BACKGROUND: Bee venom contains multiple allergens with a wide distribution of molecular weight. In contrast with conventional bee venom desensitization, peptide or recombinant allergen immunotherapy may have to take into account patients' individual patterns of humoral or cellular response. OBJECTIVE: To study immunoglobulin (Ig)E and T-cell responses to high-molecular weight bee venom allergens >/= 50 kDa. METHODS: Bee venom proteins were separated by size exclusion chromatography and fractions were characterized by one and two-dimensional gel electrophoresis. IgE antibody binding to bee venom fractions was analysed by immunoblotting and T-cell responses by proliferation assay. RESULTS: Among 38 bee venom-hypersensitive patients, IgE recognition pattern of bee venom allergens varied greatly. IgE bound mainly to phospholipase A2 and furthermore to several proteins >/= 50 kDa (50, 54, 69, 84 and 94 kDa). N-terminal sequences of these proteins showed no homology with known proteins. In addition, peripheral mononuclear cells from patients as well as from nonatopic donors strongly proliferated in response to those proteins. CONCLUSIONS: Although present in low amounts, high-molecular weight allergens from bee venom elicit strong IgE and T-cell responses, and may need to be considered as clinically relevant. Therefore, the development of peptide or recombinant protein-based immunotherapy for bee venom allergy may require careful characterization of such allergens.

Allergens↗
PubMed1999

Microheterogeneity of serum glycoproteins in patients with chronic alcohol abuse compared with carbohydrate-deficient glycoprotein syndrome type I.

BACKGROUND: Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrate-deficient transferrin isoforms. This alteration could be similar to that present in patients with carbohydrate-deficient glycoprotein syndrome type 1 (CDG1). We thus compared the alterations of N-glycans present in patients with alcoholism and patients with CDG1. METHODS: The N-glycans of serum glycoproteins were compared in sera of patients with alcoholism, patients with CDG1, and controls by two-dimensional electrophoresis, neuraminidase, peptide:N-glycosidase F, and endoglycosidase F2 treatments. A specific antibody directed against the amino acid sequence surrounding the N-432 N-glycosylation site of transferrin was prepared (SZ-350 antibody). RESULTS: In patients with alcoholism, the abnormal transferrin and alpha(1)-antitrypsin isoforms were devoid of a variable number of entire N-glycan moieties and were identical with those present in CDG1. In the serum of patients with alcoholism, this finding was less pronounced than in CDG1. In contrast to CDG1, there was no decrease in clusterin or serum amyloid P in patients with alcoholism. The SZ-350 antibody recognized only transferrin isoforms with one or no N-glycan moieties. CONCLUSION: Antibodies directed against specific N-glycosylation sites of glycoproteins could be useful for developing more specific immunochemical tests for the diagnosis of chronic alcohol abuse.

Alcoholism↗
PubMed1998

Electrophoretic analyses in a case of monoclonal gamma chain disease.

Abnormal low molecular weight immunoglobulin heavy chain can be detected in serum samples from patients with heavy chain disease. In this paper, we report the characterization of a gamma heavy chain in a patient suffering from a lymphoplasmocytic disorder, using immunofixation analysis and two-dimensional polyacrylamide gel electrophoresis. We demonstrate that the combination of serum protein agarose electrophoresis and two-dimensional electrophoresis (three-dimensional electrophoresis) can be used to further characterize abnormal protein bands detected by immunofixation.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1998

Adenosine and migraine.

BACKGROUND: Adenosine is a powerful natural vasodilator that participates in the control of cerebral and meningeal blood flow. In this context, it could be involved in the pathophysiology of migraine, since it was previously reported that intravenous adenosine can precipitate crises in migraine patients. METHODS: We have investigated circulating adenosine levels in 12 patients suffering from migraine without aura, during crises and in crisis-free periods, and have compared the levels noted to those of a population of 10 controls. To determine if there are interactions between adenosine and serotonin, we examined the effect of adenosine and antagonists on the uptake and the release of (14C) serotonin by platelets. RESULTS AND CONCLUSION: We have reached a dual conclusion: 1) during migraine headaches there is an increase (mean 68%) in circulating adenosine levels and this increase may participate in cephalalgia; 2) activation of A2 receptors by adenosine causes a dose-dependent serotonin uptake by platelets. This inhibition of uptake could participate in the rapid elimination of serotonin in migraine sufferers. As a result of this, the use of adenosine antagonists could be an effective complementary treatment for migraine.

Adenosine↗
PubMed1998

In vitro cytokine profiles as indicators of relapse activity and clinical course in multiple sclerosis.

In vitro production of tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and oligoclonal IgG (IgG OB) was evaluated in the aim to investigate their profile in correlation with multiple sclerosis (MS) clinical activity and clinical course. Whole blood stimulation with lipopolysaccharide or concanavalin A was performed in 61 patients presenting with relapsing-remitting, relapsing-progressive or chronic progressive MS; treatments received were: none, azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon-beta 1a (IFN-beta 1a) and corticosteroids (CST). The cinetics of cytokine production showed that (i) in the absence of treatment, TNF-alpha and IL-6 dropped respectively after and during the periods surrounding relapse, while IL-4 was increasing before and IL-10 after relapse; (ii) with AZA, TNF-alpha and IL-6 lowered before exacerbation, IL-4 prolonged high levels after and IL-10 before relapse; (iii) with IFN-beta 1a, IL-10 was already increasing before relapse, and TNF-alpha was higher after relapse. When cytokine levels were analysed independently from MS clinical activity, the use of AZA inhibited IgG OB and TNF-alpha synthesis (P = 0.002) but increased IL-4 (P = 0.0024), whereas IFN-beta 1a stimulated TNF-alpha and inhibited IgG OB and IL-4 production. CST inhibited TNF-alpha, IL-6, IL-4 and IgG OB synthesis. This study stresses both the weight of clinical parameters and of methodology used in results obtained in cytokine analysis in MS.

Biomarkers↗
PubMed1997

Cloning and characterization of Helicobacter pylori succinyl CoA:acetoacetate CoA-transferase, a novel prokaryotic member of the CoA-transferase family.

Sequencing of a fragment of Helicobacter pylori genome led to the identification of two open reading frames showing striking homology with Coenzyme A (CoA) transferases, enzymes catalyzing the reversible transfer of CoA from one carboxylic acid to another. The genes were present in all H. pylori strains tested by polymerase chain reaction or slot blotting but not in Campylobacter jejuni. Genes for the putative A and B subunits of H. pylori CoA-transferase were introduced into the bacterial expression vector pKK223-3 and expressed in Escherichia coli JM105 cells. Amino acid sequence comparisons, combined with measurements of enzyme activities using different CoA donors and acceptors, identified the H. pylori CoA-transferase as a succinyl CoA:acetoacetate CoA-transferase. This activity was consistently observed in different H. pylori strains. Antibodies raised against either recombinant A or B subunits recognized two distinct subunits of Mr approximately 26,000 and 24, 000 that are both necessary for H. pylori CoA-transferase function. The lack of alpha-ketoglutarate dehydrogenase and of succinyl CoA synthetase activities indicates that the generation of succinyl CoA is not mediated by the tricarboxylic acid cycle in H. pylori. We postulate the existence of an alternative pathway where the CoA-transferase is essential for energy metabolism.

Acyl Coenzyme A↗
PubMed1997

Microheterogeneity of serum glycoproteins and their liver precursors in patients with carbohydrate-deficient glycoprotein syndrome type I: apparent deficiencies in clusterin and serum amyloid P.

Serum and liver protein patterns were studied, respectively, in 5 patients (serum) and 1 patient (liver) with carbohydrate-deficient glycoprotein syndrome (CDGS) type I by high-resolution two-dimensional electrophoresis (2-DE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The pattern of serum glycoproteins in all 5 patients presented abnormal trains of isoforms with decreased mass (delta molecular weight 3000) and all showed a cathodal shift. Two-dimensional electrophoresis and SDS-PAGE mass analysis of transferrin, alpha1 -antitrypsin, haptoglobin beta-chain, and alpha1-acid glycoprotein after neuraminidase and N-glycosidase F treatments demonstrated that the additional trains of the isoforms found in CDGS type I contain homologous species of isoforms. Some of them still showed charge differences, and all still contained glycans except for transferrin, with some unusual nonglycosylated isoforms. In addition, deficiencies in clusterin and serum amyloid P, not described so far, have been found in all 5 patients. The two-dimensional pattern of immunodetected precursors of serum proteins in liver cells from 1 patient with CDGS showed abnormal low-mass precursors and the absence of the precursors normally found in controls. These results suggest that these abnormal precursors accumulate during the early oligosaccharide processing of the nascent protein-bound oligosaccharides and that glycoprotein precursors undergo an altered intracellular transport while the post-translational processing along the normal pathway is still apparently functioning in patients with CDGS.

Amyloid↗
PubMed1997

Is carbohydrate-deficient transferrin a specific marker for alcohol abuse? A study in patients with chronic viral hepatitis.

Carbohydrate-deficient transferrin, a transferrin isoform, is hailed as a new marker of chronic alcohol abuse, but its specificity is, however, not unequivocally accepted. The aim of the present study was therefore to determine carbohydrate-deficient transferrin levels in patients with chronic hepatitis B and C with or without documented chronic alcohol intake. Carbohydrate-deficient transferrin was measured using a double-antibody radioimmunoassay (CDTect, Pharmacia) in serum samples from 66 patients (45 males and 21 females; mean age: 39 years) with chronic viral hepatitis B (n = 20) or C (n = 46). Diagnosis of the underlying liver disease was established by liver biopsy. Carbohydrate-deficient transferrin levels were raised in 15 patients [23%; hepatitis B (n = 2) and hepatitis C (n = 13)]. In patients with chronic hepatitis B, the carbohydrate-deficient transferrin level was raised in two abstainers. In the 46 patients with chronic hepatitis C, 10 (22%) patients with an alcohol consumption of < 60 g/day for the men and 30 g/day for the women had raised carbohydrate-deficient transferrin levels. The overall specificity of carbohydrate-deficient transferrin for chronic alcohol abuse was thus 78%, suggesting an association between elevated carbohydrate-deficient transferrin levels and the presence of chronic viral hepatitis. Carbohydrate-deficient transferrin levels were not correlated with the histological grading or staging of chronic hepatitis B and C, or with biological markers of hepatic synthesis and cellular damage. Thus, an increased carbohydrate-deficient transferrin level may occur in patients with chronic viral hepatitis in the absence of chronic alcohol abuse. This fact should be kept in mind by physicians when using this marker to detect alcohol abuse.

Adult↗