Biomedical subjects
A Bonnin
Publications and source records attributed to A Bonnin.
Immunodetection of the microvillous cytoskeleton molecules villin and ezrin in the parasitophorous vacuole wall of Cryptosporidium parvum (Protozoa: Apicomplexa).
Microvilli - actin - villin - ezrin - Cryptosporidium parvum The sporozoites and merozoites of the Apicomplexan protozoan Cryptosporidium parvum (C. parvum) invade the apical side of enterocytes and induce the formation of a parasitophorous vacuole which stays in the brush border area and disturbs the distribution of microvilli. The vacuole is separated from the apical cytoplasm of the cell by an electron-dense layer of undetermined composition. In order to characterize the enterocyte cytoskeleton changes that occur during C. parvum invasion and development, we used both confocal immunofluorescence and immunoelectron microscopy to examine at the C.parvum-enterocyte interface the distribution of three components of the microvillous skeleton, actin, villin and ezrin. In infected cells, rhodamine-phalloidin and anti-villin and anti-ezrin antibodies recognized ring-like structures surrounding the developing parasites. By immunoelectron microscopy, both villin and ezrin were detected in the parasitophorous vacuole wall surrounding the luminal and lateral sides of the intracellular parasite. In contrast, anti-beta and anti-gamma actin antibodies showed no significant labelling of the vacuolar wall. These observations indicate that the parasitophorous vacuole wall contains at least two microvillus-derived components, villin and ezrin, as well as a low amount of F-actin. These data suggest that C.parvum infection induces a rearrangement of cytoskeleton molecules at the apical pole of the host cell that are used to build the parasitophorous vacuole.
5-Hydroxytryptamine-moduline: a novel endogenous peptide involved in the control of anxiety.
The serotonergic system is considered as a neuromodulatory system interacting with other neurotransmissions in the brain and participating in the elaboration of an adapted response of the central nervous system to external stimuli. Indeed, serotonin is involved in a large number of physiological events, such as temperature regulation, sleep, learning and memory, behaviour, sexual function, hormonal secretions and immune activity, and in parallel, it is also implicated in pathological disorders particularly in stress, anxiety, aggressivity and depression. At least 14 different types of serotonin receptors mediate serotonergic activity and among them, serotonin-1B receptors play an important role in the control of the serotonergic function. Serotonin-1B receptors are autoreceptors localized on serotonergic neuron terminals (varicosities) where they inhibit the evoked release of serotonin and its biosynthesis; they are also heteroreceptors located on non-serotonergic terminals, where they inhibit the release of the corresponding neurotransmitters (acetylcholine, GABA, noradrenaline, etc.). 5-Hydroxytryptamine-moduline, an endogenous tetrapeptide (Leu-Ser-Ala-Leu) recently isolated and characterized from rat and bovine brain extracts, was shown to specifically interact with serotonin1B receptors as an allosteric modulator having antagonistic properties in vitro and in vivo. Immuncytochemical studies using specific polyclonal anti-peptide antibodies have shown that this peptide is distributed heterogeneously in mouse brain and located in areas which also contain serotonin-1B receptors. Moreover, the content of these cerebral tissues in 5-hydroxytryptamine-moduline is affected by stress. In the present work, polyclonal anti-5-hydroxytryptamine-moduline antibodies were administered to mice via intracerebroventricular injections to study the in vivo effects of a lowering (or suppression) of this neuropeptide in the central nervous system. The inactivation of the peptide by the specific antibodies significantly modified the behaviour of the animals in two behavioural tests, the open-field and elevated plus-maze, known to be animal models related to anxiety behaviour. Treated mice displayed behaviour consistent with an anxiolytic effect of the antibody, suggesting a potential role of 5-hydroxytryptamine-moduline in the control of anxiety.
Caspase-dependent apoptosis during infection with Cryptosporidium parvum.
The protozoan parasite Cryptosporidium parvum causes persistent diarrhea and malnutrition in children and the diarrhea-wasting syndrome in AIDS. No therapy exists for eliminating the parasite in the absence of a healthy immune response. Although it had been reported that infection of intestinal cell lines with C. parvum leads to host cell death, the mechanisms of cytolysis have not been characterized. We show here that infection with C. parvum leads to typical apoptotic nuclear condensation and DNA fragmentation in host cells. Both nuclear condensation and DNA fragmentation are inhibited by a caspase inhibitor, showing that caspases are involved in this type of apoptosis. Finally, blocking apoptosis with the caspase inhibitor increases the percentage of infected cells, suggesting that parasites may use apoptosis to exit from the infected cell or that the infected cells may eliminate the parasite through apoptosis. These results suggest that apoptosis could be involved in the pathogenesis of C. parvum infections in vivo, and raise the possibility that therapeutic interference with host cell death could alter the course of the pathology in vivo.
Cirrhotic liver enhancement on dual-phase helical CT: comparison with noncirrhotic livers in 146 patients.
OBJECTIVE: The purpose of this study was to prospectively determine any differences in vascular and liver enhancement between patients with cirrhosis and patients without cirrhosis during both the arterial and portal venous phases on dual-phase helical CT. SUBJECTS AND METHODS: Fifty-eight patients with histologically proven cirrhosis (group 1) and 88 without cirrhosis (group 2 = normal findings on CT, group 3 = metastases, group 4 = other liver diseases) underwent dual-phase helical CT of the liver. Attenuation values of liver and vessels were measured on unenhanced scans and on scans obtained during the arterial and portal venous phases. The mean enhancement values per time interval (5 sec) were determined. Results were analyzed taking into account various intrinsic patient parameters. RESULTS: We found no statistically significant difference in terms of mean vascular enhancement and mean liver enhancement during the arterial imaging phase for each time interval among all the groups. The mean peak enhancement and mean liver enhancement during the portal venous phase were significantly lower in group 1 than in other groups. Time to peak enhancement was significantly delayed in group 1. CONCLUSION: In spite of the hepatic arterial buffer response, mean liver enhancement during the arterial phase was not significantly different in patients with cirrhosis compared with patients without cirrhosis. Although portal vein enhancement did not differ significantly, enhancement of cirrhotic liver was significantly lower during the portal venous phase and delayed, presumably because of decreased peripheral portal perfusion. The contrast injection protocol may be tailored to optimize conspicuity of hypovascular tumor.
[What is it? MacLeod or Swyer-James syndrome].
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[Computed tomography imaging of abdominal wall metastases after laparoscopy].
We report a case of abdominal wall metastases which occurred after diagnostic laparoscopy in a 64-year-old man presenting with gallbladder carcinoma and peritoneal carcinomatosis. CT showed enhancing masses along the laparoscopic tracts, suggesting metastatic seeding at the time of the surgery. This unusual complication fuels the current debate regarding indications of laparoscopic surgery in patients with malignancy.
[Medical tele-imaging: a good chance for the future].
Tele-imaging is an important part of telemedicine: it includes the transmission of medical digital images and plays a role in all fields of telemedicine, such as expertise, consultation, teaching and research. Tele-imaging has been made possible through the digitalization of medical imaging. There are two possibilities: either digitalization of conventional radiological film or direct acquisition of digital images. The transmission of medical imaging requires a high data rate so as to obtain a good quality transmission of the initial images in a reasonable delay. In order to deal with the great amount of information to be stocked and transmitted, a compression of the data, without loss of information, is usually necessary. Interactivity is very important in all these types of transmissions. These tele-transmission techniques are already used world wide, especially in Japan and in the United States, to help in therapeutic or diagnostic decisions. In France, we have been performing real time interactive tele-imaging sessions between radiology and endocrinology departments of Hotel Dieu in Montréal and Hôpital Cochin in Paris. This experimental device includes a visual-conference link between the medical teams and a real time link between two CT scanners. The CT scanner slices appear simultaneously both CT scanner screens; it is even possible to guide a CT scanner examination using remote control from the other hospital. We have successfully repeated the experiment between Cochin and a private hospital in Paris. In the case of the "Prison de la Santé", we have been using telemedicine in order to reduce problematic transfers of prison inmates. Moreover, access to doctors in the prison is sometimes difficult. The system ensures the daily transmission of X-rays, which are immediately read by radiologists at Cochin. In the past, 50 to 70 X-rays had to be read during one weekly visit. Medical tele-imaging raises certain legal, ethical and economic issues, such as problems concerning confidentiality, the right to compensation, patient information. It would be interesting in this context to open a discussion on the possible dangers of telemedicine, its value for the patients and the physicians, its role in emergency care, and the possibility of creating imaging data storage that may help radiologists in making diagnoses, especially for unusual images. Drawbacks not to be ignored: Poor digital images could lead to difficulties in their reading and interpretation. There is still a debate as to whether tele-diagnosis is reliable or not. Further evaluations must be made to as certain the effectiveness of these techniques. A certain dehumanization of medicine due to an increase in the distance between the physician and patient is another difficult issue. The great number of people involved in the process of tele-imaging could confuse the issue of determining individual responsibility. Such consultations of experts may reduce the freedom of patients to choose their doctor. Tele-consultation must not be performed without the patient's consent. If consent was not obtained before tele-transmission, the patient should be informed after the procedure; and the use of tele-consultation should be mentioned in the report. The utilization of public networks could lead to the manipulation of data as well as undermine confidentiality. These pitfalls must be avoided. Lastly, the financial ramifications of these new technologies must not be overlooked.
[Preliminary reflections on radiation exposure from diagnostic X-rays].
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Molecular, cellular and physiological characteristics of 5-HT-moduline, a novel endogenous modulator of 5-HT1B receptor subtype.
The serotonergic transmission is considered as a neuromodulatory system in the Central Nervous System. 5-HT1B receptors play an important role in this modulatory activity. We have purified from mammalian brain an endogenous peptide, LSAL, we called 5-HT-moduline, interacting specifically with 5-HT1B receptors. This interaction is characterized by a high affinity (Ki = 10(-10) M) and a non-competitive mechanism. Direct [3H]5-HT-moduline binding revealed a single population of sites having an apparent affinity constant close to 10(-10) M. Autoradiographic studies showed a brain distribution of [3H]5-HT-moduline binding sites closely related to the 5-HT1B receptors. In functional studies, the peptide is able to reverse the activity of a 5-HT1B agonist in the nanomolar range. Furthermore, this antagonist effect is also observed in vivo on mice behavior. Immunocytochemistry revealed an heterogeneous distribution of 5-HT-moduline in mouse brain. The labeled structures correspond to cellular profiles with axon-like prolongations. Moreover, in vitro, LSAL is released in a Ca++, K(+)-dependent manner. Therefore, 5-HT-moduline behaves as a neurotransmitter. The fact that 5-HT-moduline induces the desensitization of 5-HT1B receptors reflects the existence of a novel and efficient mechanism able to rapidly modulate the serotonergic activity.
Functional properties of 5-HT-moduline in the immune system: a model for central nervous system investigation.
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A novel multi-domain mucin-like glycoprotein of Cryptosporidium parvum mediates invasion.
Cryptosporidium parvum is a protozoan parasite which produces self-limited disease in immunocompetent hosts and devastating, persistent diarrhea in immunocompromised individuals. There is no effective treatment for cryptosporidiosis and little is known about the basic biology of the organism. Cloning and sequence analysis of the gene encoding GP900, a previously identified > 900 kDa glycoprotein, predicts a mucin-like glycoprotein composed of distal cysteine-rich domains separated by polythreonine domains and a large membrane proximal N-glycosylated core region. A trinucleotide repeat composed predominantly of the triplet ACA encodes the threonine domains. GP900 is stored in micronemes prior to appearance on the surface of invasive forms. The concentration of native GP900 which inhibits 50% (IC50) of invasion in vitro is low picomolar; the IC50 for a recombinant cysteine rich-domain is low nanomolar. These observations indicate that GP900 is a parasite ligand for a host receptor involved in attachment/invasion and suggest that immunotherapy or chemotherapy directed against GP900 may be feasible.
[Imaging of adrenal glands].
The technical choice in imaging the adrenal gland will depend on several factors discussed in the review. CT and MRI are achieving increasingly high accuracy in the investigation of patients suspected to present adrenal pathology. Scintigraphy evaluates functional patterns of both adrenal cortex and medulla, depending on the radiopharmaceutical that is used. Non invasive characterization of adrenal lesions is very important in cases of incidental discovery of adrenal masses. This review concentrates on new techniques for evaluating the incidentally discovered adrenal masses and differentiating between adrenal adenomas and metastases.
Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development.
We have determined the pharmacological characteristics of the rat 5-ht6 receptor stably expressed in CHO cells. Moreover, using RT-PCR experiments the in vivo expression of the gene encoding this receptor was studied in rat at various embryonic days (ED) starting from ED10 to birth (PN0) and at post-natal days (PN) up to PN36. The pharmacological analysis of the [3H]5-HT binding in stably transfected CHO cells expressing rat 5-ht6 receptors revealed the presence of a single class of high affinity saturable binding sites for 5-HT corresponding to an affinity constant: Kd=27.2+/-3.4 nM. This receptor also exhibited a high affinity for a number of typical and atypical antipsychotics, tricyclic antidepressant drugs and ergot alkaloïds. In stably transfected CHO cells, serotonin elicited a potent stimulation of adenylyl cyclase activity which was blocked by antipsychotic and antidepressant drugs. These results confirm the hypothesis that 5-ht6 receptors may correspond to an important target for atypical antipsychotics and reveal an original pharmacological profile for this receptor. The study of the ontogeny of the 5-ht6 mRNA in rat developing brain showed that 5-ht6 mRNA were first detectable with a high level on ED12, slighly decreased up to ED17 and then remained stable at high level until the adult age. The ontogenetic pattern of 5-ht6 mRNA expression appeared to correlate with the occurence of the first cell bodies of serotonergic neurons; the early expression of 5-ht6 mRNA and the fact that this receptor is positively coupled to the production of cAMP may suggest a role for 5-ht6 receptor in the early growth process involving the serotonergic system.
Failure to differentiate Cryptosporidium parvum from C. meleagridis based on PCR amplification of eight DNA sequences.
In order to determine the specificities of PCR-based assays used for detecting Cryptosporidium parvum DNA, eight pairs of previously described PCR primers targeting six distinct regions of the Cryptosporidium genome were evaluated for the detection of C. parvum, the agent of human cryptosporidiosis, and C. muris, C. baileyi, and C. meleagridis, three Cryptosporidium species that infect birds or mammals but are not considered to be human pathogens. The four Cryptosporidium species were divided into two groups: C. parvum and C. meleagridis, which gave the same-sized fragments with all the reactions, and C. muris and C. baileyi, which gave positive results with primer pairs targeting the 18S rRNA gene only. In addition to being genetically similar at each of the eight loci analyzed by DNA amplification, C. parvum and C. meleagridis couldn't be differentiated even after restriction enzyme digestion of the PCR products obtained from three of the target genes. This study indicates that caution should be exercised in the interpretation of data from water sample analysis performed by these methods, since a positive result does not necessarily reflect a contamination by the human pathogen C. parvum.
Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography.
OBJECTIVE: The purpose of this study was to compare dual-phase helical CT and endosonography for the diagnosis and staging of pancreatic tumors. SUBJECTS AND METHODS: Thirty patients with suspected pancreatic tumors underwent endosonography and dual-phase helical CT. A pathologic diagnosis was obtained in all cases with surgery (n = 23) or biopsy (n = 7), resulting in 27 neoplasms. Dual-phase helical CT and endosonographic findings were correlated with surgical and pathologic findings to determine diagnosis and resectability of pancreatic tumors. RESULTS: Overall diagnostic sensitivity was 92% for dual-phase helical CT and 100% for endosonography (p = .45). Overall accuracy for staging of pancreatic tumors was 93% for both dual-phase helical CT and endosonography. Overall accuracy for predicting resectability was 90% for both dual-phase helical CT and endosonography. Accuracy of predicting unresectability was 100% for dual-phase helical CT and 86% for endosonography (p > .80). Differences were not considered statistically significant. CONCLUSION: Dual-phase helical CT and endoscopic sonography do not differ significantly for diagnosis and assessment of resectability of pancreatic tumors.
[Value of high-frequency (20 MHz)in the diagnosis of cutaneous tumors].
The purpose of the present study is to asses the value of high frequency ultrasonography (20 MHz), a new noninvasive imaging technique, in cutaneous tumors. Cutaneous tumors are clinically varied and their diagnosis is still based on histopathological analysis. 140 cutaneous tumors have been examined with US and imaging findings have been compared to the results of clinical and histological examinations. This study shows that high frequency ultrasonography, even though it cannot replace pathological analysis, may help the dermatologist in the positive diagnosis of some cutaneous tumors and in accessing the location and the in depth-extension of the lesions in the different layers of the skin.
[Imaging of adrenal incidentalomas].
Imaging plays an important role in evaluating fortuitously discovered adrenal masses. These unanticipated masses (incidentalomas) are usually discovered at CT examinations. Although most incidentally discovered adrenal tumors are non-hyperfunctioning adenomas, they must be distinguished from primary or secondary malignant lesions. Recent studies have established that both unenhanced CT scans and chemical shift MR imaging can accurately differentiate benign adenomas from nonadenomatous masses by features that reflect the large amount of lipid found in most adenomas and absent in most nonadenomas. We review here the current imaging issues concerning adrenal incidentalomas including diagnostic approaches and management.