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Biomedical subjects

D Picard

Publications and source records attributed to D Picard.

At least 109 records · Page 6Linked to original sources

Cell-type preference of immunoglobulin kappa and lambda gene promoters.

Immunoglobulin gene constant regions are known to be associated with strictly tissue-specific enhancer elements. Until recently the promoter of the variable region, which becomes linked to the constant region by somatic rearrangement, could have been viewed as a passive recipient of the enhancer stimulus. Here we show that the promoters of the immunoglobulin kappa and lambda light chain genes are approximately 20-30 times more active in lymphoid cells than in non-lymphoid cells. To avoid the problem of differential mRNA stability upon transfection of immunoglobulin genes into non-lymphoid cells we have constructed chimeric genes. All kappa mRNA sequences were progressively deleted to fuse the kappa gene promoter to a globin gene coding body. A similar chimeric gene was constructed with the promoter of the lambda gene. The cell-type preference of the promoter may be exploited during B-lymphocyte differentiation to regulate the immunoglobulin gene promoter independently from the enhancer.

Animals↗

Unrearranged immunoglobulin lambda variable region is transcribed in kappa-producing myelomas.

Most cell lines which secrete immunoglobulin kappa chains retain their lambda light chain genes in the germline configuration. We report that the lambda variable (V lambda) region is nevertheless transcribed in such kappa-secreting cells at a steady-state level of 1-10 RNA molecules per cell. These transcripts are developmentally regulated since they are not detectable in cell lines representative of earlier stages of B-lymphocyte differentiation. Therefore, the same cellular components which recognize and activate the unrearranged V lambda segment may also regulate the expression of the productive immunoglobulin genes. V lambda transcripts are initiated at the lambda gene cap site, include the variable region, and extend approximately 175 nucleotides into the adjacent spacer DNA. The transcripts are polyadenylated, properly spliced and transported into the cytoplasm. Interestingly, the spacer sequence contains an open reading frame which extends the V lambda coding region for an additional 37 amino acids. It is likely that V lambda transcripts are translated into an elongated protein which may play a regulatory role in B-lymphocyte differentiation.

Amino Acid Sequence↗

Correct transcription of a cloned mouse immunoglobulin gene in vivo.

We have obtained correct transcripts from the mouse immunoglobulin lambda I light chain gene on transfection into human HeLa cells. Linkage to simian virus 40 (SV40) DNA containing a transcriptional "enhancer" element was required to raise lambda-chain gene transcription to a detectable level in our transient-expression assay. The transcripts had the same 5' end as authentic lambda I mRNA when the SV40 enhancer element was 150 base pairs upstream from the cap site. The situation was different when the lambda-chain gene promoter was separated from the SV40 sequences by more than 1 kilobase pair of spacer DNA; then, lambda-chain gene transcripts were not correctly initiated in human HeLa, monkey CV-1, and mouse 3T6 cells. In this respect, the lambda-chain gene behaves differently from the rabbit beta-globin gene, which can be activated by the SV40 enhancer over distances of several kilobases.

Animals↗

Gallium-67 imaging in pericarditis secondary to tuberculosis and histoplasmosis.

In recent years, many cases of Ga-67 uptake by the heart have been reported. One such case involved a patient with tuberculous pericarditis. Recently, a patient was referred to us for the investigation of a fever of unknown origin. A Ga-67 scan was performed and showed an intense uptake by the pericardium. The final diagnosis was pericarditis secondary to mediastinal lymph node involvement with tuberculosis and histoplasmosis.

Adolescent↗

[An experimental study of veralipride (author's transl)].

The administration of doses of 0,001, 0, 01, 0,1, and 1 mg/kg/day of veralipride to female rats produces a dose-related blocking effect on dioestrus. No histological changes are noted in the genital tract and mammary gland tissues after 0,001 and 0,01 mg/kg/day. Doses of 0,1 and 1 mg/kg/day block ovulation and the resulting estrogen impregnation modifies the appearance of the uterine glands and vaginal epithelium. Mammotropic effects, seen as a moderate hyperplasia but without galactogenic secretion, occur after 1 mg/kg/day only.

Animals↗

Cytochemical duality of neurosecretory material in the hypothalamo-posthypophysial system of the rat as related to hormonal content.

Cytochemical methods using silver proteinate, silver methenamine an potassium ferrocyanide + OsO4 for ultrastructural detection of glycoproteins allow, in the posthypophysis and the magnocellular nuclei of the rat, differentiation of two types of fibres and neurons: one type containing negative granules with a homogenous content of low electron density, the second type containing granules which demonstrate a ring shaped deposit either of silver or of potassium ferrocyanide-osmium complex, likely to be related to a glycoprotein component. The difference between these two types is increased by prestaining "en bloc" with uranyl acetate before the silver proteinate reaction. A similar investigation was carried out on the vasopressin deficient Brattleboro rat; the neurosecretory material, present in some endings and neurons only, is of the nonreactive type, so that it appears justified to correlate the reactivity of granules with vasopressin, consequently to distinguish neurones and fibres containing vasopressin from those in which oxytocin is quantitatively the main hormonal peptide. This conclusion is strongly supported by the fact that percentages of reactive and negative endings, as determined on this basis in the posthypophysis of normal rats from two different strains, are in good agreement with biochemical data reported in the literature.

Animals↗

Granulolysis in neurosecretory neurons of the rat supraoptico-posthypophyseal system.

Ultrastructural and cytochemical observations on neurosecretory neurons of the rat supraoptico-posthypophyseal systems were made under experimental conditions which resulted in striking changes in the amount of neurosecretory granules and lysosomes. Attention was focused on granulolysis. At the onset of rehydration following a 4 days water deprivation, very active autophage took place in neurosecretory axons of the neural lobe involving the marked increase in smooth endoplasmic reticulum, microvesicles and neurosecretory granules, although the latter were still very few due to previous depletion. When axonal transport was inhibited by colchicine at the onset of rehydration, granules accumulated in the perikarya while granule reloading of the neural lobe was delayed. However autophagy, although always active in axons, remained scarce in perikarya. Moreover, in the latter there was only slight evidence of crinophagy. Hypophysectomy also induced granule accumulation in the perikarya, although accompanied by little granulolysis. Images indicative of crinophagy as shown by acid phosphatase localization were few and exclusively restricted to perikarya, while autophagy occurred essentially in axons. Autophagy appeared to be the predominant process for granulolysis and might be considered here as an aspect of the general turnover of cell constituents, related to the sudden regression of hyperactivity-induced hyperthrophy, rather than as an expression of a specific regulation of an excess of secretory material.

Acid Phosphatase↗