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M Charron

Publications and source records attributed to M Charron.

At least 19 recordsLinked to original sources
PubMed2001

Role of rRAB22b, an oligodendrocyte protein, in regulation of transport of vesicles from trans Golgi to endocytic compartments.

Intracellular membrane trafficking plays an essential role in the biogenesis and maintenance of myelin. Members of the Rab protein family are important components of the systems that regulate intracellular vesicle transport. We examine the function of rRab22b, a novel rat Rab protein cloned from an oligodendrocyte cDNA library, by visualizing and identifying in living Hela cells the organelles that contain rRab22b. Our results show that rRab22b is present in the trans Golgi/TGN and endocytic compartments. Trafficking of membranes from trans Golgi to endocytic compartments takes place via small tubulo vesicular organelles containing rRab22b. The formation of vesicles in the trans Golgi also appears to be regulated by rRab22b. Additionally, our results suggest that rRab22b controls the transport of vesicles from the trans Golgi to endocytic compartments that localize in oligodendrocyte processes. That rRab22b is involved in the transport of certain proteins from trans Golgi to myelin is suggested by the evidence that certain proteins being targeted to the plasma membrane are first transported from trans Golgi to endocytic compartments.

Amino Acid Sequence↗
PubMed2001

(99m)Tc antigranulocyte monoclonal antibody imaging for the detection and assessment of inflammatory bowel disease newly diagnosed by colonoscopy in children.

OBJECTIVE: This prospective study evaluated a (99m)Tc antigranulocyte monoclonal antibody Fab' imaging agent (Sulesomab) in children with inflammatory bowel disease (IBD) newly diagnosed by colonoscopy. MATERIALS AND METHODS: Ten children (4 boys, 6 girls; mean age 14 years) with newly diagnosed Crohn's disease (n = 6) or ulcerative colitis (n = 4) were studied. Colonoscopy was performed in all of these patients. Within 24 h after colonoscopy, they underwent scintigraphy with (99m)Tc-Sulesomab. Abdominal/pelvic images were acquired at 30 min (planar) and 2-4 h (planar and SPECT) after injection of Sulesomab. Eighty bowel segments were evaluated semi-quantitatively by the investigators, using these three sets of images. The Pediatric Disease Activity (PDA) was correlated with the erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, albumin, Kirschner's score, the Sulesomab bowel segment with maximum uptake, and the sum of Sulesomab score in each segment. RESULTS: The median PDA score was 26 (range 12.5-40). Three children had normal ESR and six normal WBC counts. All patients had at least one positive mucosal biopsy for IBD. While using the Kirschner's scale, the maximal severity of colonoscopy findings was graded as none (n = 2), mild (n = 4), moderate (n = 3), or severe (n = 1). Of the 59 segments evaluated with endoscopy, 35 were found to be endoscopically abnormal. The planar images identified 17 of these abnormal segments and the SPECT images 20. Nine of these ten children had abnormal bowel uptake by scintigraphy. Thus, the sensitivity of Sulesomab per patient was 90 % and per bowel segment 57 %. The correlation coefficient between the scintigraphic score for the segment with the Sulesomab maximum activity and the PDA was 0.3 (P = 0.41). CONCLUSION: In pediatric IBD assessment, planar imaging with Sulesomab did not prove very sensitive in detecting inflammation in each bowel segment. However, SPECT detected the presence of inflammation in the majority of patients. A trial comparing (99m)Tc-HmPAO-WBC with Sulesomab in a large number of patients is required.

Antibodies, Monoclonal↗
PubMed2001

Male germ cells regulate transcription of the cathepsin l gene by rat Sertoli cells.

It is well known that male germ cells regulate the steady state levels of numerous transcripts expressed by Sertoli cells. To date, however, there has been no direct test of whether this regulation reflects changes in gene transcription and/or transcript stability. This study used two experimental approaches to test the hypothesis that germ cells regulate transcription of the cathepsin L gene by rat Sertoli cells. We examined this gene because, in vivo, steady state levels of cath L messenger RNA in Sertoli cells change in a stage-specific manner as the surrounding germ cells progress through the 14 stages of the cycle of the seminiferous epithelium. In the first experimental approach, seminiferous tubules at stages VI-VII and stages IX-XII were incubated for 1 h in 4-thiouridine, and the amount of metabolically labeled cath L messenger RNA was quantified. The results demonstrate that transcription of the cath L gene by Sertoli cells is 7-fold higher at stages VI-VII than at stages IX-XII. The second experimental approach examined the ability of germ cells to regulate the activity of cath L reporter constructs in mature Sertoli cells. Before these studies, we isolated a cath L genomic clone and demonstrated that this clone contains the transcription start site of the cath L gene expressed by Sertoli cells. Transient transfection analysis then demonstrated that two reporter constructs, containing 244 and about 2.1 kb of sequence upstream from the transcription start site, had similar activities in mature Sertoli cells. However, germ cells only affected the activity of the larger construct in Sertoli cells, which was reduced by 30%. We conclude that germ cells regulate transcription of the cath L gene by Sertoli cells and that repressive effects of germ cells are mediated by elements upstream from nucleotide -244 of this gene.

Animals↗
PubMed2001

Successful management of tracheotomized patients with chronic saliva aspiration by use of constant positive airway pressure.

OBJECTIVE: Management of chronic aspiration of saliva is a challenge to clinicians. The purpose of this report is to review the clinical course of 3 patients with tracheotomy who we have followed for at least 1 year and who have received constant positive airway pressure (CPAP) as a primary treatment for ongoing aspiration of saliva. METHODS: Retrospective chart review. RESULTS: We present here 3 patients with chronic congestion and persistent hypoxemia in whom a diagnosis of chronic aspiration of saliva was established by use of radionuclide salivagram. Each of these children had tracheotomy for treatment of airway obstruction. In an attempt to decrease chronic aspiration of saliva, we instituted constant positive pressure via tracheotomy. Repeat radionuclide salivagram performed on CPAP demonstrated a marked decrease in saliva aspiration. All patients experienced improvement in clinical symptoms and required only rare subsequent hospitalizations for respiratory disease. CONCLUSION: We suggest, based on this case series, that CPAP administered via a tracheotomy is an acceptable means of managing chronic salivary aspiration and that it may decrease respiratory complications in such patients.

Adult↗
PubMed2000

Factors associated with calcium absorption efficiency in pre- and perimenopausal women.

BACKGROUND: The amount of calcium ingested by an individual may affect several chronic conditions, including osteoporosis, hypertension, and colon cancer. However, individuals vary in their ability to absorb the calcium they consume. OBJECTIVE: The purpose of this study was to examine sources of interindividual variation in the efficiency of calcium absorption in women. DESIGN: Fractional calcium absorption was estimated in 142 healthy pre- and perimenopausal women. Dietary habits, lifestyle factors, calciotropic hormones, and vitamin D receptor gene polymorphisms were also assessed. RESULTS: Calcium absorption values averaged 35% and ranged from 17% to 58%. Fractional calcium absorption was positively associated with body mass index (r = 0.22, P = 0.007), dietary fat intake (r = 0.29, P = 0.001), serum 1,25 dihydroxyvitamin D [1,25(OH)(2)D] concentrations (r = 0.23, P = 0. 006), and parathyroid hormone concentrations (r = 0.21, P = 0.015). Fractional calcium absorption was inversely associated with total calcium intake (r = -0.18, P = 0.030), dietary fiber intake (r = -0. 19, P = 0.028), alcohol consumption (r = -0.14, P = 0.094), physical activity (r = -0.22, P = 0.007), and symptoms of constipation (r = -0.16, P = 0.059). In stepwise regression analysis, dietary fat, dietary fiber, serum 1,25(OH)(2)D, and alcohol consumption emerged as independent predictors of calcium absorption, explaining 21.02% of the observed variation. Women in the lowest tertile of the ratio of dietary fat to fiber had 19% lower fractional calcium absorption values than did women in the highest tertile of ratio of dietary fat to fiber (test of trend, P < 0.001). CONCLUSIONS: There is a wide range of calcium absorption values in healthy women. The amount of dietary fat consumed relative to dietary fiber appears to have an important role in determining differences in calcium absorption performance among individuals.

Absorption↗
PubMed2000

Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion.

PURPOSE: Hepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution were recently developed, but hepatocyte transplantation systems must be optimized. The authors report their experience with In-111 oxyquinolone labeling of a test dose of hepatocytes (108 cells) for noninvasive assessment of the biodistribution of transplanted hepatocytes in a 5-year-old child with omithine transcarbamoylase deficiency. MATERIALS AND METHODS: Donor hepatocytes (approximately 108) were radiolabeled using a commercially available In-111 oxyquinolone solution (specific activity of 1 mCi/ml). RESULTS: The overall labeling efficiency was 36.4%. A final dose of approximately 290 ,uCi of the In-111-labeled hepatocytes in 10 ml serum-free phosphate-buffered saline was infused percutaneously into the portal vein approximately 2.5 hours after their preparation. The study was performed 3 hours before cell transplantation (109 cells). Quantitative analysis of the biodistribution of In-111-labeled hepatocytes indicated that cells were predominantly localized in the liver immediately after portal vein-infused transplantation. The predominant hepatic distribution was persistent for as long as 7 days after the procedure, with an average liver-to-spleen ratio of 9.5 to 1. No significant pulmonary radiotracer uptake was present. CONCLUSION: These results indicate that In-111 labeling of hepatocytes is useful for the short-term noninvasive analysis of the biodistribution of transplanted hepatocytes.

Cell Movement↗
PubMed2000

Pediatric inflammatory bowel disease imaged with Tc-99m white blood cells.

Studies have suggested that Tc-99m white blood cell (WBC) imaging is superior to contrast radiology for assessing the extent and activity of inflammatory bowel disease (IBD). The Tc-99m WBC scan seems ideally suited to obtain, in only one examination, a precise temporal snapshot of the distribution and intensity of inflammation, whereas radiographic methods of investigation tend to represent changes that are more chronic. The test is useful in children with inconspicuous signs suggesting IBD in whom laboratory test results are either normal or slightly abnormal. In those cases, a negative Tc-99m WBC study will obviate endoscopic investigations. The author's current experience, in more than 500 patients, indicates that the Tc-99m WBC scan is a virtual gold standard to establish, or exclude, the diagnosis of IBD. The minimal invasiveness of the Tc-99m WBC scan makes it an especially attractive method for evaluating children with IBD. It is economical compared with endoscopy, and its diagnostic sensitivity is excellent. The ability to evaluate the small and large bowel simultaneously is an important advantage for the patient. In conclusion, the Tc-99m WBC scan is a useful tool to evaluate IBD and should be added to the clinician's investigative armamentarium.

Child↗
PubMed2000

Whole-body FDG positron emission tomographic imaging for staging esophageal cancer comparison with computed tomography.

PURPOSE: The aim of the authors in this study was to critically evaluate the role of whole-body positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) in staging esophageal cancer, and further to compare this method with conventional imaging with computed tomography (CT). MATERIALS AND METHODS: The authors performed independent, blinded retrospective evaluations of FDG PET images obtained in 47 patients referred for the initial staging of esophageal cancer before minimally invasive surgical staging. Twenty PET studies from patients with nonesophageal thoracic cancers were randomly selected for inclusion in the PET readings. In a subset of 37 of 47 cases, the PET findings were compared with independent readings of CT studies acquired within the same 6-week interval. The utility of the imaging findings was evaluated using a high-sensitivity interpretation (i.e., assigning equivocal findings as positive) and a low-sensitivity interpretation (i.e., assigning equivocal findings as negative). RESULTS: PET was less sensitive (41% in high-sensitivity mode, 35% in low-sensitivity mode) than CT (63% to 87%) for diagnosing tumor involvement in locoregional lymph nodes, which was identified by surgical assessment in 72% of patients. Notable, however, was the greater specificity of PET-determined nodal sites (to approximately 90%) compared with CT (14% to 43%). In detecting histologically proved distant metastases (n = 10), PET performed considerably better when applied in the high-sensitivity mode, with a sensitivity rate of approximately 70% and a specificity rate of more than 90% in the total group and in the subset of patients with correlative CT data. In the low-sensitivity mode, CT identified only two of seven metastatic sites, whereas the high-sensitivity mode resulted in an unacceptably high rate of false-positive readings (positive predictive value, 29%). PET correctly identified one additional site of metastasis that was not detected by CT. CONCLUSIONS: The relatively low sensitivity of PET for identifying locoregional lesions precludes its replacement of conventional CT staging. However, the primary advantage of PET imaging is its superior specificity for tumor detection and improved diagnostic value for distant metastatic sites, features that may substantially affect patient management decisions. In conclusion, PET imaging is useful in the initial staging of esophageal cancer and provides additional and complementary information to that obtained by CT imaging.

Adenocarcinoma↗
PubMed2000

Image analysis in patients with cancer studied with a combined PET and CT scanner.

PURPOSE: To compare combined whole-body PET and CT images of different cancers with PET images alone. MATERIALS AND METHODS: Thirty-two patients with known or possible cancers were examined using a combined positron emission tomographic (PET) and computed tomographic (CT) scanner. All data were acquired using this same combined scanner. After an injection of F-18 fluorodeoxyglucose (FDG), noncontrast helical CT imaging of the neck, chest, abdomen, or pelvis was performed. The spiral CT was followed by a PET scan covering the same axial extent as the CT. RESULTS: Coregistered PET-CT images identified and localized 55 lesions. In 10 patients (31%), areas with variable amounts of normal physiologic FDG uptake were distinguished from potential uptake of FDG in a nearby neoplastic lesion. Improved localization was achieved in 9 patients (for a total of 13 lesions, or 24%). CONCLUSION: Combined PET-CT images appear more effective than PET images alone to localize precisely neoplastic lesions and to distinguish normal variants from juxtaposed neoplastic lesions.

Aged↗
PubMed2000

Are 99mTc leukocyte scintigraphy and SBFT studies useful in children suspected of having inflammatory bowel disease?

OBJECTIVE: The goal of this retrospective study was to assess whether 99mTc-white blood cell (WBC) scintigraphy and upper gastrointestinal small bowel follow-through (UGI-SBFT) could exclude inflammation in children suspected of having inflammatory bowel disease (IBD). METHODS: Of a population of 313 children who had a 99mTc-WBC scan, 130 children were studied exclusively to rule out IBD. Sixty-nine colonoscopies with biopsies were done within a short time interval of the 99mTc-WBC scans. There were also 51 controls studied with 99mTc-WBC scintigraphy. RESULTS: Of the 130 children studied to exclude IBD, the final diagnosis was Crohn's disease in 27, ulcerative colitis in nine, miscellaneous colitis in 13, probably normal in 42, and normal in 39. The 99mTc-WBC scans were positive in all but three newly diagnosed Crohn's disease, ulcerative colitis, or miscellaneous colitis children. The false-negative 99mTc-WBC studies were seen in children with mild inflammation on biopsies and normal UGI-SBFT studies. In the 46 children with a true-positive 99mTc-WBC scan, 81% (17/21) of UGI-SBFT studies were normal. In five children with equivocal UGI-SBFT studies, the 99mTc-WBC scan correctly predicted if inflammation was present in the terminal ileum. CONCLUSIONS: Our results suggest that 99mTc-WBC is useful as an initial screening modality to exclude IBD, and is more sensitive than UGI-SBFT studies.

Adolescent↗
PubMed2000

A combined PET/CT scanner for clinical oncology.

UNLABELLED: The availability of accurately aligned, whole-body anatomical (CT) and functional (PET) images could have a significant impact on diagnosing and staging malignant disease and on identifying and localizing metastases. Computer algorithms to align CT and PET images acquired on different scanners are generally successful for the brain, whereas image alignment in other regions of the body is more problematic. METHODS: A combined PET/CT tomograph with the unique capability of acquiring accurately aligned functional and anatomical images for any part of the human body has been designed and built. The PET/CT scanner was developed as a combination of a Siemens Somatom AR.SP spiral CT and a partial-ring, rotating ECAT ART PET scanner. All components are mounted on a common rotational support within a single gantry. The PET and CT components can be operated either separately, or in combined mode. In combined mode, the CT images are used to correct the PET data for scatter and attenuation. Fully quantitative whole-body images are obtained for an axial extent of 100 cm in an imaging time of less than 1 h. When operated in PET mode alone, transmission scans are acquired with dual 137Cs sources. RESULTS: The scanner is fully operational and the combined device has been operated successfully in a clinical environment. Over 110 patients have been imaged, covering a range of different cancers, including lung, esophageal, head and neck, melanoma, lymphoma, pancreas, and renal cell. The aligned PET and CT images are used both for diagnosing and staging disease and for evaluating response to therapy. We report the first performance measurements from the scanner and present some illustrative clinical studies acquired in cancer patients. CONCLUSION: A combined PET and CT scanner is a practical and effective approach to acquiring co-registered anatomical and functional images in a single scanning session.

Adult↗
PubMed1999

Gastric and small bowel Crohn's disease assessed with leukocytes-Tc(99m) scintigraphy.

We reviewed 312 (99m)Tc leukocyte (99m)Tc-WBC studies to evaluate the sensitivity and specificity of (99m)Tc-WBC for identifying small-bowel and gastric inflammation in children with Crohn's disease. The (99m)Tc-WBC scans were interpreted blindly and compared to the results of colonoscopy with biopsies and surgical specimens. In 46 children, total colonoscopy was done within a few days of a (99m)Tc- WBC scan and in 13 others surgical specimens were available. Of the 37 children in whom the terminal ileum was visualized endoscopically (24) or surgically (13), the WBC-Tc(99m) scan showed a similar degree of inflammation in 33. The sensitivity of (99m)Tc-WBC scanning was 91% and the specificity 96%. The scans allowed evaluation of inflammation in the terminal ileum in 22 children in whom the endoscopist did not cannulate it; the scans were abnormal in 10 of these 22 children. In the children with no ileoscopy the results of the (99m)Tc-WBC scan were consistent with the laboratory values, the gastroenterologist's clinical assessment, and long-term clinical follow-up. Finally, the scans of 46 controls did not reveal any false-positive findings in the terminal ileum. Five children with gastritis documented by gastroscopy had normal (99m)Tc-WBC scans and upper gastrointestinal barium studies. This study demonstrates in a large number of normal and abnormal children with different pre-test probabilities of having inflammatory bowel disease that scintigraphy is reliable in identifying small-bowel inflammation.

Adolescent↗
PubMed1999

Technetium leukocyte imaging in inflammatory bowel disease.

Technetium-99m white blood cell ((99m)Tc-WBC) imaging has been part of the initial evaluation and follow-up of more than 400 children presenting with inflammatory bowel disease (IBD) at Children's Hospital of Pittsburgh. Studies have suggested that (99m)Tc-WBC imaging is superior to contrast radiology in assessing the extent and activity of IBD. With only one examination, (99m)Tc-WBC imaging is ideally suited to obtain a precise temporal snapshot of the distribution and intensity of inflammation, whereas radiography tends to detect more chronic changes. There is a high correlation between (99m)Tc-WBC imaging findings and those of endoscopy. When total colonoscopy cannot be completed satisfactorily or when contrast radiography findings are negative or equivocal, scintigraphy can confirm the presence of ileitis or right-sided colitis. Occasionally, (99m)Tc-WBC imaging is useful in differentiating Crohn's disease from ulcerative colitis. Some studies have suggested that (99m)Tc-WBC imaging is useful as an initial screening modality to exclude IBD. Technetium-99m WBC imaging is noninvasive, practical, safe, requires no bowel preparation, and entails less radiation exposure than contrast radiology or computed tomography.

Child↗
PubMed1999

Assessment of terminal ileal and colonic inflammation in Crohn's disease with 99mTc-WBC.

We evaluated the sensitivity and specificity of Technetium-99m (99mTc)-white blood cell (WBC) for identifying terminal ileum inflammation in children with Crohn's disease (CD). In 40 children, total colonoscopy was done within a few days of a 99mTc-WBC scan carried out to evaluate the inflammation in children with CD. In 38 patients the intensity and the location of inflammation shown on the 99mTc-WBC scan of the colon were similar to the biopsy result of the colonoscopy. The sensitivity of the 99mTc-WBC scan was 97% in assessing colonic inflammation compared with colonoscopy. The 99mTc-WBC scan allowed evaluation of inflammation in the terminal ileum in 21 patients in whom the endoscopist did not cannulate the terminal ileum. Of the 19 patients in whom the terminal ileum was visualized endoscopically (14) or surgically (5), the 99mTc-WBC scan findings showed a similar degree of inflammation in 17. The 99mTc-WBC scan was abnormal in 10 of these 21 children in whom the gastroenterologist did not reach the terminal ileum. In these children with no ileoscopy the results of the 99mTc-WBC scan were consistent with the laboratory values, the gastroenterologist's clinical assessment and with long-term clinical follow-up. Finally, the 99mTc-WBC scan of 83 controls did not reveal any false-positive findings in the terminal ileum (colonoscopy result available in 30 controls). When total colonoscopy or ileoscopy is not performed or when contrast radiography is negative or unable to differentiate CD from lymphoid nodular hyperplasia, scintigraphy can demonstrate the presence of ileitis and/or colitis.

Adolescent↗
PubMed1999

A novel 14-base-pair regulatory element is essential for in vivo expression of murine beta4-galactosyltransferase-I in late pachytene spermatocytes and round spermatids.

During murine spermatogenesis, beginning in late pachytene spermatocytes, the beta4-galactosyltransferase-I (beta4GalT-I) gene is transcribed from a male germ cell-specific start site. We had shown previously that a 796-bp genomic fragment that flanks the germ cell start site and contains two putative CRE (cyclic AMP-responsive element)-like motifs directs correct male germ cell expression of the beta-galactosidase reporter gene in late pachytene spermatocytes and round spermatids of transgenic mice (N. L. Shaper, A. Harduin-Lepers, and J. H. Shaper, J. Biol. Chem. 269:25165-25171, 1994). We now report that in vivo expression of beta4GalT-I in developing male germ cells requires an essential and previously undescribed 14-bp regulatory element (5'-GCCGGTTTCCTAGA-3') that is distinct from the two CRE-like sequences. This cis element is located 16 bp upstream of the germ cell-specific start site and binds a male germ cell protein that we have termed TASS-1 (transcriptional activator in late pachytene spermatocytes and round spermatids 1). The presence of the Ets signature binding motif 5'-GGAA-3' on the bottom strand of the TASS-1 sequence (underlined sequence) suggests that TASS-1 is a novel member of the Ets family of transcription factors. Additional transgenic analyses established that an 87-bp genomic fragment containing the TASS-1 regulatory element was sufficient for correct germ cell-specific expression of the beta-galactosidase reporter gene. Furthermore, when the TASS-1 motif was mutated by transversion, within the context of the original 796-bp fragment, transgene expression was reduced 12- to 35-fold in vivo.

Animals↗