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Biomedical subjects

C Hirth

Publications and source records attributed to C Hirth.

At least 19 recordsLinked to original sources
PubMed2000

Antioxidant and immune status in active Crohn's disease. A possible relationship.

BACKGROUND AND AIMS: As reactive oxygen has been demonstrated to participate in immune genes transcription, the aim of this study was to examine the relationship between systemic concentrations of several antioxidants and markers of inflammatory and immune activation in patients with Crohn's disease (CD). METHODS: In 26 CD patients and 15 controls we compared plasma selenium and zinc concentrations, erythrocyte glutathione peroxidase (GSHPx) and superoxide dismutase activities, as well as erythrocyte sedimentation rate (ESR), C-reactive protein, tumor necrosis factor-alpha, interleukin-6, blood neopterin and soluble receptors of interleukin-2 (sIL-2R), and examined the link between these parameters. RESULTS: Selenium concentration and GSHPx activity were decreased in CD patients (54.5 +/- 3.2 vs 79 &plusmn 2.2 microg/l, P<< 0.05; 28 +/- 1.6 vs 38 +/- 2.6 IU/g Hb, P<< 0.05) and positively correlated to each other's (r= 0.59, P<< 0.01). TNF-alpha was significantly increased in patients (18 +/- 2.6 vs 5 +/- 0.6 pg/ml;P<< 0.001), negatively correlated to GSHPx activity (r= -0.56, P<< 0.05) and selenium concentration (r= -0.72, P<< 0.001), and positively to neopterin and sIL-2R concentrations. Selenium showed negative correlation with sIL-2R (r= -0.83, P<< 0.0001) and ESR. CONCLUSIONS: In CD patients low selenium concentration may participate in reduced GSHPx activity facilitating inflammatory and immune activation. In these patients, selenium monitoring and, if needed, supplementation may be of therapeutical interest.

Adult↗
PubMed2000

Noninvasive functional imaging of human brain using light.

Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatio-temporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring.

Adult↗
PubMed1997

Simultaneous assessment of cerebral oxygenation and hemodynamics during a motor task. A combined near infrared and transcranial Doppler sonography study.

During performance of a sequential finger opposition task we measured changes in regional cerebral blood oxygenation (rCBO) over the motor cortex and blood flow velocity changes (CBFV) in the middle cerebral artery in a combined near-infrared spectroscopy (NIRS) and transcranial Doppler Sonography (TCD) study. Stimulus duration was 60 followed by a 90 s rest period. During performance of the motor task we observed an increase in [oxy-Hb] a decrease in [deoxy-Hb] and an increase in MCA flow velocity. These changes were significantly more pronounced contralaterally than ipsilaterally to the moving hand. The time course of changes in [oxy-Hb] and CBFV were strikingly similar, showing a pronounced initial over-shoot. This study proves the feasibility of a simultaneous assessment of microcirculatory hemodynamics and cerebral oxygenation at high temporal resolution.

Adult↗
PubMed1997

Length of resting period between stimulation cycles modulates hemodynamic response to a motor stimulus.

The influence of different lengths of the pre-stimulation resting period on the magnitude of a hemodynamic response evoked by motor stimulation was examined in 10 subjects by means of near-infrared spectroscopy (NIRS). A motor stimulus was used which has been previously established as a model for functional activation studies with NIRS. Subjects performed a 20 s finger opposition task in the hand contralateral to NIRS probe localization over left sensorimotor area (C3', according to the 10-20 system). The duration of the pre-stimulation resting period was varied from 10s to 50s and response magnitude was assessed for each of the interstimulus intervals (10 s, 20 s, 30 s, 40 s and 50 s). Data analysis showed that response magnitude in oxygenated and deoxygenated haemoglobin concentration changed with different interstimulation intervals. Interestingly the greatest NIRS response was obtained with resting period 30 s prior to stimulation; shorter and longer resting periods resulted in smaller responses. The time course and the dependence of response magnitude on interstimulus interval differed between [oxy-Hb] and [deoxy-Hb] changes. For [oxy-Hb] the previously described fast initial increase ('overshoot') and the post-stimulation undershoot was more clearly seen with long prestimulation resting periods. Cytochromeoxidase oxygenation changes did not change significantly with different interstimulus intervals. We conclude that comparisons between different functional activation studies with techniques relying on stimulus evoked changes in cerebral hemodynamics must take into account not only the quality of the experimental paradigm and the length of the stimulation period, but also that the resting period between repetitive stimulations is important for response amplitude and its time course.

Brain↗
PubMed1997

High-pass-filtered magnetocardiogram and cardiomyopathy in patients with type 1 diabetes mellitus.

Prolonged and/or fractionated depolarization due to tissue degeneration of the ventricular myocardium is a feature of cardiomyopathy. Signal averaged electrocardiography uses high-pass filters of the Butterworth type to quantify, noninvasively, fractionated high-frequency components at the end of the QRS complex. In this study a finite impulse response high-pass filter of the 90th order (cutoff at 37 Hz) was applied to magnetocardiograms (MCGs) and high-resolution electrocardiograms (ECGs) order to quantify high-frequency components throughout the myocardial depolarization. Additionally, late-potential analysis on the signal-averaged ECG was performed. A prospective investigation was made of 23 cardiologically asymptomatic patients, 11 females and 12 males, with type I diabetes mellitus. Their mean age was 21.7 years (range, 13-34 years). The mean duration of diabetes was 14 years (range, 1-27 years). Data were compared with those of 22 control subjects (12 females, 10 males) of mean age, 23.2 years (range, 11-35 years). The ECGs and MCGs were simultaneously recorded and signal-averaged, digitally filtered, and quantified by a score obtained by multiplying the amplitude variation of the signal by the number of maximal/minimal in the QRS complex. Echocardiograms were used to calculate the left ventricular mass and to document the presence of cardiomyopathy. Scores were higher in the MCGs of with type I diabetes mellitus than in the control subjects (P < .001). High scores correlated with an increased left ventricular muscular mass index (P < .05) and duration of the diabetes (P < .05). The high-resolution ECG, processed analogously, showed similar results in relation to left ventricular mass (P = .06) and duration of diabetes (P = .07), respectively (nonsignificant). No late potentials were found. These findings suggest that using a linear-phase high-pass finite impulse response filter may be useful for the noninvasive identification of patients with cardiomyopathy who exhibit possible disturbances of intraventricular depolarization. Our findings also suggest that analysis using the total QRS complex, rather than the final part of the QRS complex only, may improve identification of patients at risk.

Adolescent↗
PubMed1996

Non-invasive functional mapping of the human motor cortex using near-infrared spectroscopy.

We applied non-invasive multisite near-infrared spectroscopy (NIRS) to assess oxygenation changes during performance of a sequential finger opposition task in five healthy human adults. Oxygenation response was localized anatomically using three-dimensional high-resolution magnetic resonance imaging (3D MRI). NIRS measurements showed a localized increase in [oxy-Hb] and a decrease in [deoxy-Hb] in all subjects. The largest response was obtained when the measurement position was over the primary motor and sensory cortex hand area. Interestingly, changes in [deoxy-Hb] seemed to be more localized than changes in [oxy-Hb]. We conclude that this simple, non-invasive and flexible optical bedside method may be used for functional brain mapping.

Adult↗
PubMed1996

Novel photoactivatable agonist of the nicotinic acetylcholine receptor of potential use for exploring the functional activated state.

The nicotinic acetylcholine receptor (AChR) exhibits at least four different conformational states varying in affinity for agonists such as acetylcholine (ACh). Photoaffinity labeling has been previously used to elucidate the topography of the AChR. However, to date, the photosensitive probes used to explore the cholinergic binding site photolabeled only closed or desensitized states of the receptor. To identify the structural modifications occurring at the ACh binding site on allosteric transition associated with receptor activation, we have investigated novel photoactivatable 4-diazocyclohexa-2,5-dienone derivatives as putative cholinergic agonists. Such compounds are fairly stable in the dark and generate highly reactive carbenic species on irradiation. In binding experiments using AChRs from Torpedo marmorata, these ligands had affinities for the ACh binding site in the micromolar range and did not interact with the noncompetitive blocker site (greater than millimolar affinity). Irreversible photoinactivation of ACh binding sites was obtained with the ligand 1b (up to 42% at 500 microM) in a protectable manner. In patch-clamp studies, 1b was shown to be a functional agonist of peripheral AChR in TE 671 cells, with the interesting property of exhibiting no or very little desensitization even at high concentrations.

Acetylcholine↗
PubMed1996

Cerebral oxygenation changes in response to motor stimulation.

We studied cerebral hemodynamic response to a sequential motor task in 56 subjects to investigate the time course and distribution of blood oxygenation changes as monitored by near-infrared spectroscopy (NIRS). To address whether response is modulated by different performance velocities, a group of subjects (n = 12) was examined while performing the motor task at 1, 2, and 3 Hz. The results demonstrate that 1) the NIRS response reflects localized changes in cerebral hemodynamics, 2) the response, consisting of an increase in oxygenated hemoglobin concentration [oxy-Hb] and a decrease in deoxygenated hemoglobin concentration ([deoxy-Hb]), is lateralized and increases in amplitude with higher performance rates, and 3) changes in [oxy-Hb] and [deoxy-Hb] differ in time course. Changes in [oxy-Hb] are biphasic, with a fast initial increase and a pronounced poststimulus undershoot. The stimulus-associated decrease in [deoxy-Hb] is monophasic, and response latency is greater. We conclude that NIRS is able to detect even small changes in cerebral hemodynamic response to functional stimulation.

Adult↗
PubMed1996

Abnormal urinary coproporphyrin levels in patients infected by hepatitis C virus with or without human immunodeficiency virus. A study of 177 patients.

OBJECTIVE: Many cases of porphyria cutanea tarda have been described in association with human immunodeficiency virus (HIV) infection in young individuals. The link between hepatitis C virus (HCV) and porphyria cutanea tarda is even stronger as more than 50% of patients who have this diagnosis in Italy, France, or Spain are also infected by HCV. To study the role of viral infections on the metabolism of porphyrins, we measured the urinary porphyrin levels in patients with HIV and HCV infections. DESIGN: Survey; prospective study. SETTING: University Hospital of Strasbourg, France. PATIENTS: Sixty-one HIV-positive patients, 56 HCV-positive patients, 60 HIV- and HCV-positive patients, and 51 HIV- and HCV-negative control subjects were randomly selected. None had clinical signs of porphyria or a familial history of porphyria. MAIN OUTCOME MEASURES: The porphyrin-excretion profile was determined by high-performance liquid chromatography on fresh urine samples. The HIV and HCV viremias were quantified in the serum by the branched DNA assay. Measures were planned before data collection began. RESULTS: The porphyrin-excretion profile typical of porphyria cutanea tarda was found in only 1 of 177 patients. In the remaining 176 patients, the mean coproporphyrin level was significantly raised in HCV-positive patients and even higher in patients who were HIV- and HCV-positive. The coproporphyrin level was not correlated to the alanine aminotransferase level, the CD4+ cell count, or the HCV and HIV viremias. CONCLUSIONS: In cases of infection with HIV, HCV, or both, the development of a porphyria cutanea tarda urinary profile is a rare event (0.56% in this study), but coproporphyrin excretion is increased. This could be related to hepatic changes induced by the viruses. Our results do not support the hypothesis of a direct viral effect on the porphyrin metabolism. Infection with HIV, HCV, or both may be a major triggering factor, but is not sufficient to induce porphyria.

Adolescent↗
PubMed1994

Trp279 is involved in the binding of quaternary ammonium at the peripheral site of Torpedo marmorata acetylcholinesterase.

Specific photoaffinity labelling of purified acetylcholinesterase from Torpedo marmorata by p-N,N-[3H]dimethylamino benzenediazonium and p-N,N-[3H]dibutylamino benzenediazonium derivatives was demonstrated. This occurred at the active site of the enzyme for lower concentrations of the probes and at the peripheral ammonium binding site for higher concentrations. The affinities and the rate constants of alkylation for each probe on both sites have been established. Specific labelling at the peripheral site of the enzyme with both probes allowed the identification of radio-labelled peptides having the common sequence K270PQELIDVEW. The radioactivity was always associated with the residue Trp279 indicating the preferential ammonium complexation with this aromatic residue.

Acetylcholinesterase↗
PubMed1994

In vivo binding of [125I]NH2-carfentanil to mu opioid receptors in mouse brain.

A functionalized derivative of the mu opioid agonist carfentanil was synthesized (NH2-carfentanil) and showed high specific activity when radiolabeled with iodine. [127I]NH2-carfentanil displayed high affinity and pronounced mu-binding selectivity with a delta/mu selectivity ratio of over 1200. The ability of [125I]NH2-carfentanil to interact in vivo with opioid receptors was determined in mouse brain using ex vivo binding techniques. Twenty minutes after intraperitoneal injection, 0.1% of the [125I]NH2-carfentanil injected into the mouse was present in the brain. [125I]NH2-carfentanil specific binding was inhibited by co-injection of naloxone or morphine while naltrindole, a delta-selective antagonist, was unable to displace the bound radioligand. Autoradiographic experiments revealed a heterogeneous distribution of [125I]NH2-carfentanil specific binding sites, maximal binding occurred in areas with high densities of mu receptors. Peripherally administered iodo-NH2-carfentanil selectively labelled central mu opioid receptors in mouse indicating great potential for single photon emission computed tomography studies.

Animals↗
PubMed1994

[Recommended methods for the determination of catecholamines and their metabolites in urine. Significance of results in the diagnosis and follow-up of pheochromocytoma and neuroblastoma].

Laboratory investigation of catecholamines is useful for the clinician in the diagnosis and management of phaeochromocytoma and neuroblastoma. This work summarizes current knowledge on catecholamines and their metabolites and discusses the main indications for their determination. It also examines the most practical methods for studying the secretion of these hormones, ie extraction, separation and quantification using high performance liquid chromatography coupled with electrochemical detection. The workshops attended by the members of the catecholamines working party of the French Clinical Biology Society and phaeochromocytoma and neuroblastoma specialists enabled the role of such determinations in the diagnosis and management of these diseases to be clarified.

Adolescent↗
PubMed1993

Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase.

Binding sites of Torpedo acetylcholinesterase (EC 3.1.1.7) for quaternary ligands were investigated by x-ray crystallography and photoaffinity labeling. Crystal structures of complexes with ligands were determined at 2.8-A resolution. In a complex with edrophonium, and quaternary nitrogen of the ligand interacts with the indole of Trp-84, and its m-hydroxyl displays bifurcated hydrogen bonding to two members of the catalytic triad, Ser-200 and His-440. In a complex with tacrine, the acridine is stacked against the indole of Trp-84. The bisquaternary ligand decamethonium is oriented along the narrow gorge leading to the active site; one quaternary group is apposed to the indole of Trp-84 and the other to that of Trp-279, near the top of the gorge. The only major conformational difference between the three complexes is in the orientation of the phenyl ring of Phe-330. In the decamethonium complex it lies parallel to the surface of the gorge; in the other two complexes it is positioned to make contact with the bound ligand. This close interaction was confirmed by photoaffinity labelling by the photosensitive probe 3H-labeled p-(N,N-dimethylamino)benzenediazonium fluoroborate, which labeled, predominantly, Phe-330 within the active site. Labeling of Trp-279 was also observed. One mole of label is incorporated per mole of AcChoEase inactivated, indicating that labeling of Trp-279 and that of Phe-330 are mutually exclusive. The structural and chemical data, together, show the important role of aromatic groups as binding sites for quaternary ligands, and they provide complementary evidence assigning Trp-84 and Phe-330 to the "anionic" subsite of the active site and Trp-279 to the "peripheral" anionic site.

Acetylcholine↗
PubMed1993

Mite-allergen exposure and spontaneous histamine release in monosensitive and polysensitive mite-allergic patients.

Forty-three patients allergic to mites and suffering mainly from asthma were recruited: 25 were mite-monosensitive and 18 were polysensitive, as determined by skin tests and specific serum IgE determinations with various allergens. In vitro spontaneous histamine release (SHR) by washed blood basophils was measured once or several times for each patient. Throughout this study, the mean periods of high and low mite-allergen exposure were defined on the basis of relative indoor humidity and temperature data. For the mite-monosensitive patients, there was a significant increase in mean SHR during the season of high mite-allergen exposure as compared to the months of lower mite-allergen presence (P < 0.002). No significant difference between mean SHR values was observed when comparing the monosensitive group during the season of high mite-allergen exposure with polysensitive patients (allergic to mite and pollen) during the period of exposure to both allergens. Differences in mean SHR reported here emphasize the positive relationship between intense allergen exposure and the in vitro SHR increase in blood basophils of mite-allergic patients.

Adult↗
PubMed1992

A photoactivatable naltrexone derivative labels glycoproteins of different molecular weight corresponding to the mu- and kappa-opioid receptors.

The synthesis and characterization of a novel opioid receptor photoaffinity probe [3H]naltrexyl urea phenylazido derivative ([3H]NUPA) is described. In the absence of light, [3H]NUPA binds with high affinity in a reversible and saturable manner to rat brain and guinea pig cerebellum membranes. Dissociation constants and binding capacities (Scatchard plots) are 0.11 nM and 250 fmol/mg of protein for rat brain and 0.24 nM and 135 fmol/mg of protein for guinea pig cerebellum. Competition experiments indicate that this ligand interacts with high affinity at both mu- and kappa-opioid binding sites while exhibiting low affinity at delta sites (Ki = 21 nM). On irradiation, [3H]NUPA incorporates irreversibly into rat brain and guinea pig cerebellum membranes. SDS gel electrophoresis of rat brain membranes reveals specific photolabeling of a 67-kDa molecular mass band. Conversely, a major component of 58 kDa and a minor component of 36 kDa are obtained from [3H]NUPA-labeled guinea pig cerebellum membranes. Different photolabeling patterns are obtained in rat brain (mu/delta/kappa, 4/5/1) and guinea pig cerebellum (mu+delta/kappa, 1,5/8,5) membranes in the presence of selective opioid ligands indicating labeling of mu and kappa sites, respectively. Thus, [3H]NUPA behaves as an efficient photoaffinity probe of mu- and kappa-opioid receptors, which are probably represented by distinct glycoproteins of 67 and 58 kDa, respectively.

Affinity Labels↗
PubMed1992

Role and environment of the conserved Lys27 of snake curaremimetic toxins as probed by chemical modifications, site-directed mutagenesis and photolabelling experiments.

The positive charge of Lys27 was suppressed by chemical means in two short-chain curaremimetic toxins, namely erabutoxin a (Ea) from Laticauda semifasciata and toxin alpha from Naja nigricollis. This modification leads to a decrease in the binding affinity of the toxins for the nicotinic acetylcholine receptor, which range 6-15-fold, as judged from both the data reported here and those previously described in the literature. A negatively charged glutamate residue has been introduced at position 27 of erabutoxin a by site-directed mutagenesis. This change provokes a 120-fold decrease in the affinity, which reflects a major alteration of toxin-receptor cognate events. Using toxin-alpha derivative harbouring a photoactive group at Lys27, we probed the toxin local environment in a receptor-bound state by photocoupling experiments. The delta chain was the predominant coupling target, in contrast to previous observations indicating that a photoactive probe on Lys47 predominantly labelled the alpha chain. The toxin derivative weakly labelled the alpha and gamma chains but not the beta chain. The toxin may therefore interact with subunits other than the alpha chain, at least in the vicinity of Lys27.

Amino Acid Sequence↗