Measurement of skeletal muscle motion in vivo with phase-contrast MR imaging

The ability to measure skeletal muscle motion with phase-contrast magnetic resonance (MR) imaging was tested with a motion phantom that simulated muscle activity. Quantitative analytic data on unidimensional, bidirectional skeletal muscle motion measured in vivo was obtained in four healthy volunteers. MR images of the subjectss' forearms were obtained during flexion and extension of the fingers and of the anterior and posterior muscle compartments of the lower leg with various resistances to ankle dorsiflexion and plantar flexion. It was necessary to correct the data for the effects of eddy currents. In vitro evaluation of the technique was done by studying through-plane sinusoidal motion of solid objects. The largest error was underestimation of the peak excursion of 11.5 mm by 0.09 mm (the root mean square error for the cycle was 0.04 mm) In vivo experiments demonstrated the contraction of muscles in relation to each other. Data acquisition and analysis techniques must be refined, but measuring skeletal muscle motion with phase-contrast MR imaging should enhance the understanding of bioengineering fundamentals and muscular changes in disease and adaptation.     

Time-resolved MR imaging by automatic data segmentation

A method for time-resolved imaging that provides a flexible trade-off between imaging time and temporal resolution is presented. It is based on a view order selection technique that automatically segments the acquired raw data into appropriate temporal frames. When used with cardiac monitoring and phase-contrast imaging, data similar to that obtained with a conventional gated phase-contrast sequence are acquired rapidly. For many applications, the temporal resolution can be reduced enough to permit imaging within a breath-hold interval, while still allowing accurate time-averaged flow quantitation. This is a general technique that can be implemented within a variety of pulse sequences and can resolve other motion cycles, including the respiratory cycle.     

Le DRESS syndrome, une réaction d''hypersensibilité aux médicaments, qui reste mal connue des pédiatres

The DRESS syndrome (Rash with Eosinophilia and Systemic Symptoms) is a drug hypersensitivity reaction poorly known by paediatricians. It occurs within 1 to 8 weeks of treatment. Clinical features associate in variable patterns, fever, rash, lymphadenopathies, arthritis and potentially life-threatening damage (hepatitis, nephritis, pneumonitis), hyperleucocytosis and eosinophilia. This condition must be early recognized in order to immediately stop suspect drugs. A 6.5 year old girl had a febrile rash, hyperleucocytosis, lymph nodes and cytolitic hepatitis probably due to phenobarbital. Diagnosis of DRESS syndrome was performed only 13 days after the beginning of the eruption. Evolution was favorable but characterized by the recurrence of the febrile eruption with pleuritis. DRESS syndrome is a well described disease that occurs during treatment with a number drugs, particularly anti-epileptic drugs. Steroid therapy and immunoglobulins are proposed for treatment but have not been evaluated.     

Myocardial perfusion and function in dogs with moderate coronary stenosis

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl=1.077 ± 0.15 versus ANT:POS StD=0.477 ± 0.11, P<0.03) and was confirmed with radio-labeled microspheres measurements (ANT:POS Cntl=1.18 ± 0.2 ml/min/g versus ANT:POS StD=0.44 ± 0.1 ml/min/g; P<0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P<0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P=NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl=0.964 ± 0.02 versus StD=0.884 ± 0.03; P<0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.     

Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer

Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.     

Role of bacterial products in periodontitis: immune response in gnotobiotic rats monoinfected with Eikenella corrodens.

The development of humoral and cell-mediated immune responses to Eikenella corrodens (a bacterium that causes periodontal lesions in gnotobiotic rats) was measured and compared with the rate of appearance of macroscopic lesions. A possible inverse relationship was found. A strong cell-mediated immune response, as measured by skin reactivity and lymphocyte mitogenesis, occurred between 4 and 6 weeks after infection and subsided soon thereafter to a low response level. Humoral antibodies to endotoxin from E. corrodens could not be detected at any time. The disease developed only after the cell-mediated immune response diminished, thus suggesting that lack of an efficient immune response may permit the development of the disease. This is seemingly in contradiction to the assumption that tissue destruction in such cases is caused by the immune response and its products. We are inclined to believe, based on our findings reported here, that the lack of immune responsiveness to the bacterium and/or its products is the major causative factor in the development of periodontitis. At the same time, we wish to emphasize that occurrence of both phenomena during the long development of periodontal disease is possible.     

Effects of increasing osmolality on rat ileal smooth muscle

The effects of changing bathing medium osmolality on tension generation in smooth muscle were studied on potassium-depolarized segments of rat ileum. Increasing the tonicity of the medium evokes a transient relaxation of the smooth muscle; restoration of isotonicity evokes a transient contraction of similar amplitude and time course. While immersed in hypertonic media of less than 1.3 times normal tonicity, the smooth muscle slowly increases its isometric tension; in media of nearly twice normal tonicity, the smooth muscle loses tension. All of these effects occur whether the medium is made hypertonic with added NaCl or sucrose.     

An extended association screen in multiple sclerosis using 202 microsatellite markers targeting apoptosis-related genes does not reveal new predisposing factors

Apoptosis, the programmed death of cells, plays a distinct role in the etiopathogenesis of Multiple sclerosis (MS), a common disease of the central nervous system with complex genetic background. Yet, it is not clear whether the impact of apoptosis is due to altered apoptotic behaviour caused by variations of apoptosis-related genes. Instead, apoptosis in MS may also represent a secondary response to cellular stress during acute inflammation in the central nervous system. Here, we screened 202 apoptosis-related genes for association by genotyping 202 microsatellite markers in initially 160 MS patients and 160 controls, both divided in 4 sets of pooled DNA samples, respectively. When applying Bonferroni correction, no significant differences in allele frequencies were detected between MS patients and controls. Nevertheless, we chose 7 markers for retyping in individual DNA samples, thereby eliminating 6 markers from the list of candidates. The remaining candidate, the ERBB3 gene microsatellite, was genotyped in additional 245 MS patients and controls. No association of the ERBB3 marker with the disease was detected in these additional cohorts. In consequence, we did not find further evidence for apoptosis-related genes as predisposition factors in MS.     

Mice with neonatally induced inactivation of the vascular cell adhesion molecule-1 fail to control the parasite in Toxoplasma encephalitis

Under various inflammatory conditions, cell adhesion molecules are up-regulated in the central nervous system (CNS) and may contribute to the recruitment of leukocytes to the brain. In the present study, the functional role of vascular cell adhesion molecule (VCAM)-1 in Toxoplasma encephalitis (TE) was addressed using VCAM(flox/flox MxCre) mice. Neonatal inactivation of the VCAM-1 gene resulted in a lack of induction of VCAM-1 on cerebral blood vessel endothelial cells, whereas the constitutive expression of VCAM-1 on choroid plexus epithelial cells and the ependyma was unaffected; in these animals, resistance to T. gondii was abolished, and VCAM(flox/flox MxCre) mice died of chronic TE caused by a failure to control parasites in the CNS. Although leukocyte recruitment to the CNS was unimpaired, the B cell response was significantly reduced as evidenced by reduced serum levels of anti-T. gondii-specific IgM and IgG antibodies. Furthermore, the frequency and activation state of intracerebral T. gondii-specific T cells were decreased, and microglial activation was markedly reduced. Taken together, these data demonstrate the crucial requirement of VCAM-1-mediated immune reactions for the control of an intracerebral infectious pathogen, whereas other cell adhesion molecules can efficiently compensate for VCAM-1-mediated homing across cerebral blood vessels.     

Retinoids and spermatogenesis: lessons from mutant mice lacking the plasma retinol binding protein.

Using Rbp4-null mice as models, we have established for the first time the kinetics of the spermatogenetic alterations during vitamin A deficiency (VAD). Our data demonstrate that the VAD-induced testicular degeneration arises through the normal maturation of germ cells in a context of spermatogonia differentiation arrest. They indicate that retinoic acid (RA) appears dispensable for the transition of premeiotic to meiotic spermatocytes, meiosis, and spermiogenesis. They confirm that RA plays critical roles in controlling spermatogonia differentiation, spermatid adhesion to Sertoli cells, and spermiation, and suggest that the VAD-induced arrest of spermatogonia differentiation results from simultaneous blocks in RA-dependent events mediated by RA receptor gamma (RARgamma) in spermatogonia and by RARalpha in Sertoli cells. They also provide evidence that expression of major RA-metabolizing enzymes is increased in mouse Sertoli cells upon VAD and that vitamin A-deficient A spermatogonia differ from their RA-sufficient counterparts by the expression of the Stra8 gene.