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Biomedical subjects

D Picard

Publications and source records attributed to D Picard.

At least 91 records · Page 5Linked to original sources
PubMed1988

Both immunoglobulin promoter and enhancer sequences are targets for suppression in myeloma-fibroblast hybrid cells.

When immunoglobulin (Ig)-producing B cells are fused with fibroblastic cells, expression of Igs is suppressed by a mechanism that selectively abolishes transcription of Ig genes. The suppression is also maintained in proliferating hybrids. We have used gene transfer followed by cell fusion to study this phenomenon further. Here we report that expression of a rearranged Ig heavy chain gene, stably integrated into a myeloma genome, is completely suppressed upon fusion with fibroblasts by a mechanism that is equally active on the endogenous myeloma lambda light chain gene. To define regulatory sequences within the Ig transcriptional unit that are involved in this down-regulation, we examined the transcriptional contributions of the IgH chain gene enhancer and the kappa light chain gene promoter individually by linking them to a heterologous reporter gene. Mouse myeloma cells were stably transformed with such test constructs and subsequently fused with mouse fibroblasts. To avoid any significant loss of chromosomes, hybrid cells were isolated shortly after fusion by fluorescence-activated cell sorting, and proliferating hybrids were harvested within 2-3 weeks. On the basis of RNase protection mapping of cytoplasmic RNA, and of nuclear run-on assays we showed that both the kappa light chain promoter and the IgH chain enhancer contain regulatory information that is made redundant or is suppressed in the hybrid environment.

Animals↗
PubMed1988

Gallium-67 pulmonary uptake in eosinophilic pneumonia.

Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed.

Gallium Radioisotopes↗
PubMed1988

Spinal cerebrospinal fluid leak demonstrated by radioisotopic cisternography.

Many conditions are known to cause a cerebrospinal fluid (CSF) fistula; one of them is lumbar puncture for contrast myelography. Reported here is the case of a man who underwent contrast myelography at the L2-L3 level and who presented with postural headaches and lumbalgia with radiation to the legs three weeks after the procedure. Tc-99m albumin isotopic cisternography at the L5-S1 level was performed and clearly depicted a functional CSF leak through the dura at the L2-L3 level and CSF suffusion along several rachidian roots. Scinticisternography may thus be used to localize accurately a CSF leak.

Adult↗
PubMed1988

Premenopausal bone mineral content relates to height, weight and calcium intake during early adulthood.

The influence of dietary and anthropometric factors on bone mineral content was studied in 183 healthy premenopausal French-Canadian women aged between 40 and 50 years and living in the same area. Dietary evaluation of their calcium (Ca), caffeine and alcohol intake since the age of 20 was performed in all cases. Age, height, weight, exercise level, cigarette smoking, parity and estrogen were also recorded. Bone mineral content of the L2 to L4 vertebrae (BMCL, n = 183) and forearm (BMCF, n = 137) were measured respectively by dual and single photon absorptiometry. While stepwise regression analysis showed a significant relationship between total BMCL and height, weight and Ca intake, this only occurred with weight and Ca intake when BMCL was corrected for height of L2-L4 (BMCL/cm) or for bone scan area of L2-L4 (BMCL/cm2). BMCF expressed per unit of length correlated to height only. When subjects were divided into three groups according to their Ca intake (less than 500 mg/day, between 500 and 1000 mg/day and greater than 1000 mg/day), the mean BMC adjusted for significant covariables (height and weight) was statistically different for the low and high intake groups at both sites (BMCF, F = 3.9, P = 0.02; BMCL, F = 4.2, P less than 0.02; BMCL/cm, F = 6.1, P less than 0.005; BMCL/cm2, F = 4.4, P less than 0.02). These findings indicate that, of the variables considered, Ca intake, height and weight were the only significant factors related to bone mass in our homogeneous population. It is therefore suggested that Ca intake in early adulthood influences the axial and appendicular bone mass in premenopausal women.

Adult↗
PubMed1988

Scintigraphic study of duodenal-gastric reflux in cases of primary gastropathy, chronic ulcer of the duodenal bulb, and Moynihan's disease.

There are several methods for detection of bile in the stomach, but none has proven satisfactory. It appears that the scintigraphic study with quantitation of duodenal-gastric reflux after corrections for the overlap of the stomach by the liver and bowel is more reliable, noninvasive, and physiologic. Fifty-four patients were divided into groups according to their clinical presentation; seven asymptomatic volunteers, 20 patients with duodenal-gastric reflux gastropathy (DRG), 16 patients with recurrent ulcers of the duodenal bulb (RUD), and 11 patients with Moynihan's disease. Each of the 47 dyspeptic patients underwent an endoscopic examination and a scintigraphic study with [99mTc]disofenin for detection and quantitation of duodenal-gastric reflux. Endoscopy revealed the presence of bile in the stomach of 16 out of 20 DRG and four out of 16 RUD, while ten out of 11 patients with Moynihan's disease had clear gastric juice. Most of the DRG cases (15 out of 20) and half of the RUD (eight out of 16) presented reflux greater than 1.5%, while of the 11 Moynhihan, ten presented reflux less than 1.5% and all the asymptomatic volunteer subjects less than 1%. This quantitation method allowed us to perceive clearly the low % of reflux in the "normal asymptomatic" subjects compared with the DRG-type of dyspeptic patients. Among the dyspeptic, the distinction seems more evident between the DRG type and the Moynihan type. Occasionally, the scintigraphic method permits identification of patients with slower gallbladder evacuation (eight out of 47 dyspeptic in our study), adding valuable information for the diagnostic approach to dyspeptic patients.

Adult↗
PubMed1987

Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor.

We have detected nuclear localization signals within the 795 amino acid rat glucocorticoid receptor. Using a transient expression assay, we monitored by immunofluorescence the subcellular distribution of receptor derivatives and beta-galactosidase-receptor fusion proteins. Two distinct nuclear localization signals, NL1 and NL2, were defined. NL1 maps to a 28 amino acid segment closely associated, but not coincident with the DNA binding domain; NL2 resides within a 256 amino acid region that also includes the hormone binding domain. Most importantly, nuclear localization of fusion proteins containing either the full-length receptor or the NL2 region alone is fully hormone-dependent; similar results were obtained with the wild-type receptor, provided the analysis was performed in medium lacking serum and phenol red. The rate of hormone-induced nuclear localization of an NL2-containing fusion protein is consistent with the rapid kinetics of hormone-regulated transcription mediated by the receptor. Thus, hormonal control of nuclear localization contributes to the modulation of glucocorticoid receptor transcriptional regulatory activity.

Amino Acid Sequence↗
PubMed1987

Localization of abnormal parathyroid gland(s) using thallium-201/iodine-123 subtraction scintigraphy in patients with primary hyperparathyroidism.

Tl-201/I-123 subtraction scintigraphy was performed in 17 patients with clinical symptoms and biochemical measurements suggestive of primary hyperparathyroidism. Nineteen abnormal sites were identified. These results were correlated with PTH measurements and surgical findings. Three sites were considered unrelated to the parathyroid glands, two corresponding to palpable thyroid nodules and one to muscle uptake of unknown origin. One scintigram did not reveal either of two abnormal glands while two others were considered falsely positive in view of surgical failure. Fourteen sites corresponded to abnormal parathyroid gland at surgery; five glands, weighing more than 2000 mg, could be correctly located on the Tl-201 scintigraphy prior to the subtraction procedure; six glands, weighing between 500 and 2000 mg, were easily localized after the subtraction procedure; three glands, weighing between 180 and 200 mg, were correctly localized after further manipulation of the subtraction procedure. In a patient with parathyroid hyperplasia, one gland, weighing 150 mg, was not located and another was not found upon surgery. Overall sensitivity was 87.5%. A positive correlation between PTH levels, tumor weight, and ease of detection on scintigraphy was found. This correlation was particularly useful in excluding large abnormal uptake related to thyroid disorder or artifact. The results suggest that Tl-201/I-123 parathyroid scintigraphy could become an alternative to Tl-201/Tc-99m parathyroid scintigraphy, with possibly improved detection of low weight abnormal parathyroid glands.

Adenoma↗
PubMed1987

Indium-111 leukocyte scanning of the abdomen. Analysis of its value for diagnosis and management of inflammatory bowel disease.

Indium-111 leukocyte scanning of the abdomen (IAS) was performed in 10 patients with ulcerative colitis and in 39 patients with Crohn's disease involving the small intestine (in 25 occasions) and/or the colon (17 cases). Radionuclide uptake by the gut was seen in 84% of the patients with active inflammation. We compared the extent of the disease displayed by IAS with the findings obtained by either radiological or endoscopic studies or at surgery. In two-thirds of the patients, the IAS gave an accurate evaluation of the extent of the disease (sensitivity 68%). False-positive IASs were not seen in small bowel disease (specificity 100%), but were observed on 4 occasions on the colon (specificity 86%). The intensity of the radionuclide uptake could not be correlated with the clinical activity of the disease as evaluated by the Crohn's disease activity index. These results suggest that IAS is not superior to the standard procedures used to detect and localize inflammatory bowel disease and that IAS cannot replace these techniques. However, the simplicity of IAS and the complete lack of complications associated with its use render it useful in the evaluation of the extent and distribution of inflammation in some patients, mainly those with severe disease in whom standard diagnostic procedures would be contraindicated.

Abdomen↗
PubMed1987

Budd-Chiari syndrome: typical and atypical scintigraphic aspects.

Budd-Chiari syndrome, a well known entity, is often difficult to diagnose, mostly due to the nonspecificity of its symptomatology. Radiocolloid liver scans were evaluated in eight cases of this disease, proven by surgical biopsy. Five cases showed the "classic" scintigraphic pattern of caudate lobe hypertrophy (62.5%), and other abnormalities observed included segmental hepatic insufficiency, diffuse hepatic insufficiency, and relative hypertrophy of both the caudate lobe and a portion of the parenchyma of segment VI (one case each). An experimental study of hepatic venous drainage performed on livers at autopsy revealed four groups of accessory hepatic veins in addition to the main hepatic veins. The occlusion of various parts of this drainage appears to relate to the various scintigraphic patterns that were encountered in patients with Budd-Chiari syndrome. A review of the literature revealed three additional patterns previously reported in association with Budd-Chiari syndrome (normal scan, diffuse hepatomegaly, and multiple filling defects). If all these variations are appreciated, liver scanning can be a valuable screening tool for Budd-Chiari syndrome and may also serve as a noninvasive means of follow-up.

Budd-Chiari Syndrome↗
PubMed1986

During B-cell differentiation enhancer activity and transcription rate of immunoglobulin heavy chain genes are high before mRNA accumulation.

During differentiation of B lymphocytes, a low level of immunoglobulin heavy chain gene transcripts is apparent at the pre-B-cell stage, and a dramatic increase in immunoglobulin mRNA level is seen after stimulated B cells have matured into immunoglobulin-secreting plasma cells. We have measured the transcription rate of endogenous heavy chain genes using cell lines representative of various stages of murine B-lymphocyte differentiation. We observe a good correlation between RNA polymerase density, as determined by nuclear run-on transcription experiments, and the activity of the heavy chain gene enhancer, as assayed by transfection experiments. Both enhancer activity and heavy chain gene transcription are very high in pre-B-cell lines. Thus we conclude that the increased accumulation of immunoglobulin heavy chain mRNA in immunoglobulin-secreting plasma cells is regulated mainly by posttranscriptional processes.

Actins↗
PubMed1986

Abdominal patterns of indium-111 labeled leukocyte imaging.

In-111 oxine WBC abdominal scanning is now a widely accepted technique for the detection of abdominal infectious processes. High sensitivity and specificity are achieved. In-111 labeled leukocyte accumulation, however, does not always suggest the diagnosis of abscess. Higher specificity could be obtained by the knowledge of the In-111 leukocyte distribution pattern in the abdomen in other pathologic states like inflammation of abdominal wounds, stoma; surgical complication without abscess formation; inflammatory or ischemic bowel disease; or swallowing leukocytes which subsequently are visualized in the intestinal lumen. One hundred fifty-two consecutive WBC scans performed over 18 months were reviewed and classified according to their pattern of uptake: 96 cases showed no abdominal uptake, and 56 had accumulation of leukocytes in the abdomen. Twenty-eight of these patients had proven abdominal abscess, and the remaining 26 were positive due to other causes. This report briefly discusses the distribution pattern of In-111 labeled leukocytes in the latter patients and compares the results obtained using different diagnostic criteria.

Abdomen↗
PubMed1985

Evidence for transient requirement of the IgH enhancer.

A transcriptional enhancer is thought to play a major role in determining tissue-specific expression of the immunoglobulin heavy chain (IgH) gene (1-3). However in three B-lymphoid cell lines the Ig enhancer has been lost due to a spontaneous deletion, yet heavy chain synthesis persists at a high level (4-6). In the case of the enhancerless delta chain gene (5) we wanted to test whether the IgH enhancer is no longer necessary for maintenance of transcription or whether perhaps a new enhancer was created de novo by the deletion process. To this end we have cloned the relevant portion of the variant IgH gene and transfected it into myeloma and hybridoma cells. We find that the reintroduced gene segment is not expressed unless it is linked again to an enhancer. The results suggest that the IgH enhancer is necessary for the onset of transcription, presumably by organizing the gene into stable transcription complexes, but is dispensable at later stages once the transcription unit is activated.

Animals↗