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Biomedical subjects

J M Garnier

Publications and source records attributed to J M Garnier.

At least 91 records · Page 5Linked to original sources

In situ mapping of the chicken progesterone receptor gene and the ovalbumin gene.

The chicken progesterone receptor (cPR) gene and the ovalbumin (OA) gene, a target of cPR regulation, have been mapped via fluorescent in situ hybridization to the two largest chromosomes of the chicken karyotype. cPR is subtelomeric on the long arm of chromosome 1 and OA is on the long arm of chromosome 2, close to the centromere. A 35-kb cosmid probe for the cPR gene and two genomic fragments of 9.2 and 15 kb for the OA gene were biotin-labeled for nonradioactive localization of the two chicken loci.

Animals↗

Human choline acetyltransferase (CHAT): partial gene sequence and potential control regions.

Choline acetyltransferase (CHAT) (EC 2.3.1.6) is the biosynthetic enzyme for the neurotransmitter acetylcholine in the central and peripheral nervous systems. In this study, a human CHAT genomic clone has been isolated and partially sequenced at its 5' end. This fragment contains the first four exons with an ACG initiator codon and potential control regions including TATA, CAAT, GC boxes, and several transcription control sequences. A comparison of the primary structure of CHAT among pig, rat, mouse, and Drosophila is presented.

Amino Acid Sequence↗

[Pseudo-tumoral form of urinary bilharziasis in a child].

A tumor-like form of urinary schistosomiasis is reported. Diagnosis was established intraoperatively. The finding of hematuria and of a stay in an area where schistosomiasis is endemic suggested the diagnosis but specific investigations were negative. Cystoscopy revealed a budding, hemorrhagic tumor lying against the posterior aspect of the bladder with no other lesions suggestive of schistosomiasis. The true prevalence of these tumor-like forms of urinary schistosomiasis is analyzed. Emphasis is put on the need for using several investigations to reach the correct diagnosis.

Child↗

[Imipramine withdrawal syndrome during a treatment for enuresis].

The authors report on an observation of imipramine withdrawal syndrome which appeared when tapering the treatment of a case of bed-wetting. Symptoms included vomiting, digestive intolerance and dehydration. Such a presentation can mislead diagnosis towards abdominal or neurosurgical pathology. All symptoms disappeared after a symptomatic treatment or in combination with the return of imipramine. It is therefore important to be aware of this complication before prescribing imipramine treatment for enuresis. The discontinuation of this drug must be very progressive.

Adolescent↗

[Endoscopic bronchial exploration under local anesthesia in children].

One hundred and forty-two flexible fiberoptic bronchoscopies were carried out in 1 year, under local anaesthesia, in 123 children aged between 15 days and 17 years. Indications were tuberculosis (n = 26), persistent pneumonia (n = 20), suspected foreign body or control after extraction (n = 18), asthma (n = 17), atelectasis (n = 14), recurrent pneumonia (n = 13), opportunistic pneumonia (n = 11), permanent bronchial obstruction (n = 10), miscellaneous disease (n = 13). Fiberoptic bronchoscopy was abnormal in 101 patients (80%) and led to a change in the treatment in 84 cases (68%). True complications (n = 5) were all transient and were followed by complete recovery. Flexible fiberoptic bronchoscopy under local anaesthesia is a simple and safe procedure. It is an essential diagnostic and therapeutic tool in the management of pediatric respiratory disorders.

Adolescent↗

[Hydatid cyst of the kidney in the child].

Three pediatric cases of hydatic cyst of the kidney are reported. This is a very rare condition in children. Usually, the presentation is a cystic space-occupying lesion of the kidney. Several diagnostic methods are available but it is stressed that ultrasonography may be sufficient. Surgical treatment is still necessary.

Child↗

Chicken poly(ADP-ribose) synthetase: complete deduced amino acid sequence and comparison with mammalian enzyme sequences.

The complete nucleotide (nt) sequence of the cDNA encoding the chicken poly(ADP-ribose) synthetase has been determined. Positive clones overlapping the 5' region or the 3' region of the cDNA have been isolated from a lambda gt 10 hen oviduct cDNA library using two human cDNA probes. The missing middle portion has been obtained by the polymerase chain reaction procedure. A single 3033-nt open reading frame from start codon to stop codon encodes a sequence of 1011 amino acid residues. The alignment of this sequence with those from human and mouse reveals overall identities of 79% and 77%, respectively. However, an identity of about 82% is obtained in the DNA-binding domain within the two zinc fingers, and an even higher similarity (85-87%) is observed in the NAD-binding domain. The isolated clones consistently hybridize on chicken Northern blots to an mRNA species of about 4 kb, whereas they do not cross-hybridize with RNA blots of Drosophila melanogaster. Thus, it appears that, even if the functional properties of the enzyme are maintained, the cDNA identity will be much decreased in nonvertebrate organisms.

Amino Acid Sequence↗

Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1.

We describe the cDNA encoding the SV40 transcriptional enhancer factor 1 (TEF-1) and show that its translation initiates exclusively at an AUU codon in vivo. Cloned TEF-1, which is unrelated to other known transcription factors, specifically binds the SV40 GT-IIC and Sph enhansons. Cloned TEF-1 does not activate these enhansons in lymphoid MPC11 cells where they are known to be inactive, but represses the endogenous HeLa TEF-1 activity in vivo and in vitro. Repression is also observed with chimeras where the DNA-binding domain of the GAL4 activator replaces that of TEF-1, showing that repression results from interference/squelching. Such chimeras stimulate transcription in HeLa, but not in MPC11, cells in vivo and in HeLa cell extracts in vitro. However, high concentrations result in self-interference/squelching. These results strongly suggest that the trans-activation function of TEF-1 is mediated by a highly limiting, possible cell-specific, titratable transcriptional intermediary factor(s).

Amino Acid Sequence↗

Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid.

Together with the previously described mouse retinoic acid receptor alpha-1 (mRAR-alpha 1, formerly mRAR-alpha 0), we have isolated and characterized here a total of seven mRAR-alpha cDNA isoforms (mRAR-alpha 1 to alpha 7). These isoforms are generated from mRAR-alpha primary transcript(s) of a single gene by alternative splicing of at least eight different exons with the exon which encodes the amino acid sequence of their common B region. All of these isoforms differ in their 5'-untranslated regions (5'-UTRs) and, in the case of mRAR-alpha 1 and alpha 2, also in the sequences encoding the N-terminal A region which is known to be important for differential trans-activation by other members of the nuclear receptor superfamily. In addition, the sequences encoding the open reading frames (ORFs) of mRAR-alpha 3 and alpha 4 cDNA isoforms remain open to their very 5' ends, which suggests that these two isoforms may also encode RAR-alpha s with unique A region amino acid sequences. The two predominant isoforms, mRAR-alpha 1 and alpha 2, were found to be differentially expressed in mouse adult and fetal tissues, as well as in P19 and F9 embryonal carcinoma (EC) cell lines. Interestingly, the expression of mRAR-alpha 2, in contrast to that of the mRAR-alpha 1 isoform, was induced by retinoic acid (RA) in EC cells, thus suggesting the presence of two promoters in the 5' region of the mRAR-alpha gene, which differ in their response to RA. The conservation between mouse and human RAR-alpha 1 and alpha 2 cDNA isoform sequences, as seen by cross-hybridization in Southern blots or by DNA sequence analysis, together with their differential patterns of expression, strongly suggests that they perform specific functions during embryogenesis and in the adult.

Amino Acid Sequence↗

Differentially expressed isoforms of the mouse retinoic acid receptor beta generated by usage of two promoters and alternative splicing.

Using anchored PCR, three different cDNA isoforms of the mouse retinoic acid receptor beta [mRAR-beta 1, mRAR-beta 2 (formerly mRAR-beta 0) and mRAR-beta 3], generated from the same gene by differential promoter usage and alternative splicing, were isolated. These three isoforms encode RAR proteins with different N-terminal A regions and identical B - F regions. The sequence encoding the first 59 amino acids of the mRAR-beta 3 A region is identical with the entire A region of mRAR-beta 1. However, the sequence of mRAR-beta 3 region A differs from that of mRAR-beta 1 by an additional 27 C-terminal amino acids encoded in an 81 nucleotide-long putative exon which is spliced in between the exons encoding the A and B regions of mRAR-beta 1. Both mRAR-beta 1 and beta 3 cDNAs differ entirely from mRAR-beta 2 in their 5'-untranslated (5'-UTR) and A region coding sequences. This N-terminal variability, in a region which was shown to be important for cell-type specific differential target gene trans-activation by other nuclear receptors, suggests that the three mRAR-beta isoforms may be functionally distinct. The conservation of RAR-beta isoform sequences from mouse to human, as seen by cross-hybridization on Southern blots or DNA sequence analysis, as well as their differential patterns of expression in various mouse tissues, corroborates this view. Additionally, the mRNA analysis data suggest that mRAR-beta 2, whose expression predominates in RA-treated embryonal carcinoma (EC) and embryonic stem (ES) cells, may be important during early stages of development. mRAR-beta 1 and beta 3, on the other hand, which are predominantly expressed in fetal and adult brain, may play some specific role in the development of the central nervous system.

Amino Acid Sequence↗

Effect of nifedipine on glucose potentiation of the acute insulin response to arginine in non-insulin-dependent diabetics.

The effect of 7-days of nifedipine treatment on insulin secretion has been analyzed in hypertensive patients with non-insulin-dependent mellitus (NIDDM). Pancreatic beta-cell function was assessed as insulin release following stimulation with arginine after potentiation by hyperglycaemia. Two groups of 5 patients with NIDDM (fasting blood glucose 139.2 mg.dl-1), on the same controlled diet, were compared; one was treated with nifedipine 30 mg per d and the other was the control. The mean blood pressure in the nifedipine group decreased (110 vs 102 mm Hg). Fasting blood glucose and basal plasma insulin were not affected by nifedipine. The acute insulin response (AIR) to 5 g arginine after potentiation by hyperglycaemia (clamped at 240 and 350 mg/dl for 30 min) was significantly (P less than 0.05) decreased, as well as the potentiation slope (line relating AIR and plasma glucose level) in those patients, and were unchanged in the control group. Thus, nifedipine may impair insulin secretion at high glucose levels in patients with NiDDM.

Aged↗

[Extrinsic allergic alveolitis. Apropos of a severe case].

A case of atypical extrinsic allergic alveolitis in a 13-year-old is reported. Onset was sudden with gradually increasing dyspnea on exertion over a four-day period. The chest film evidenced a reticulonodular syndrome with decreased respiratory movements. The patient's clinical status worsened over the next 48 hours with the development of respiratory distress. Under oxygen therapy (3 l/min), PO2 was 49 mmHg and SO2 was 82%. Dramatic improvement occurred after initiation of corticosteroid and antimicrobial therapy. Etiologic investigations were negative except for the immunofluorescence test with pigeon droppings which showed three precipitation arcs. A CT scan of the chest disclosed diffuse micronodular densities without thickening of connective tissue trabeculae, suggesting alveolar disease. Mediastinal lymph nodes were not enlarged. Vital capacity was 26% of the theoric value. Corticosteroids were given for one month. On follow-up chest films, the reticulomicronodular syndrome was seen to abate, globally at first, then from the apices to the bases of the lungs. However, a repeat CT scan at the 4th month showed that diffuse lesions were still present although the chest film was normal; 8 months after onset, there was only a bulla in the left lung base, with no evidence of fibrosis. Lung function tests slowly returned to normal, as did CT scan findings.

Adolescent↗

Isolation and characterization of an expressed hypervariable gene coding for a breast-cancer-associated antigen.

A human gene and cDNA coding for a breast-cancer-associated antigen (H23Ag) were isolated and characterized. The gene contains two exons and one intron. Part of the second exon is a tandem repeat array (TRA) consisting of multiple 60-bp G + C-rich units. We report here the characterization of unique sequences that are found in the H23Ag gene and cDNA, in addition to the 60-bp repeats. Analysis of the cDNA sequences revealed a putative ATG start codon preceded by two overlapping initiation consensus sequences (CCACC). The open reading frame determines an amino acid (aa) sequence consisting of three regions. The first region contains an initiating methionine and a highly hydrophobic putative signal peptide. This is followed by a variable number of highly conserved 20-aa repeat units (TRA). The last region, C-terminal to TRA, contains four potential N-linked glycosylation sites. The genomic nucleotide sequences demonstrate a putative promoter region that includes a 'TATA' box. A putative estrogen regulatory element is located 5' to the promoter region. The characterization of the gene and cDNA coding for the H23Ag presented here, may help to elucidate its possible function in human breast cancer.

Amino Acid Sequence↗

Transient expression of human and chicken progesterone receptors does not support alternative translational initiation from a single mRNA as the mechanism generating two receptor isoforms.

Two isoforms (A and B) of the human (hPR) and chicken (cPR) progesterone receptors originate from a single PR gene. cPR form A results from initiation of translation at a downstream ATG codon (ATG2) which in the cPR cDNA-deduced open reading frame is found 128 amino acids C-terminal to and in-frame with the first ATG codon (ATG1) that gives rise to form B. Our recent observation of an abundant cPR mRNA which encodes only form A suggested to us that the two isoforms are translated from different transcripts (Jeltsch, J. M., Turcotte, B., Garnier, J. M., Lerouge, T., Krozowski, Z., Gronemeyer, H., and Chambon, P. (1990) J. Biol. Chem. 265, 3961-3974). This view is, however, at variance with data obtained by transient transfection with expression vectors containing most of the cPR cDNA (downstream of nucleotide +53) since both isoforms were generated in transiently transfected COS cells (Conneely, O. M., Kettelberger, D. M., Tsai, J. J., Schrader, W. T., and O'Malley, B. W. (1989) J. Biol. Chem. 264, 14062-14064). To further support our above conclusion, vectors containing either hPR or cPR cDNAs were introduced into HeLa and COS-1 cells. Only hPR form B originated from a vector containing the entire cDNA (containing nucleotides 1 to approximately 4400), and form A was produced only from a vector expressing hPR transcripts (nucleotides 814 to approximately 4400) lacking ATG1. Vectors expressing the 5'-untranslated and coding region of the cPR mRNA (nucleotides 29-2921) generated only traces of form A in the two cell lines. Similar traces of form A were observed in COS-1 cells transfected with a vector lacking the 5'-untranslated region. Collectively, these results do not support the hypothesis that similar amounts of the two PR isoforms are generated by alternative initiation of translation on a single PR transcript. We discuss data indicating that for hPR and cPR, isoforms A and B are in fact translated from different mRNAs.

Animals↗

Characterization of multiple mRNAs originating from the chicken progesterone receptor gene. Evidence for a specific transcript encoding form A.

The structure of the 42-kilobase (kb) long chicken progesterone receptor (cPR) gene and of all six transcripts that are detectable on Northern blots was determined. The first of 8 exons encodes the N-terminal region A/B which is highly divergent among different species and contains a constitutive transcription activation function. The DNA (DBD)- and hormone-binding domains (HBD) are assembled from 2 and 5 exons, respectively, with the individual "zinc fingers" of the DBD encoded by separate exons. In addition to the previously described 4.5-kb cPR mRNA species, alternative polyadenylation, splicing variation, and "5'-truncation" lead to the generation of 5 further mRNAs. Most importantly, this 5'-truncation produces, by an as yet unidentified mechanism, an abundant transcript which encodes form A but not form B of cPR. Lack of splicing at the exon 2 splice-donor and polyadenylation due to a signal site in the second intron generates a previously undetected 3.4-kb mRNA species. The corresponding cDNA was sequenced in its entirety and shown to encode only region A/B and the N-terminal "finger" of the DBD. Alternative polyadenylation upstream of the signal site for the 4.5-kb mRNA is responsible for the appearance of a 3.3-kb mRNA. The longest cPR mRNA (8.2 kb) originates from a transcription termination point more than 3 kb downstream of the 4.5-kb mRNA 3'-end. Finally, the primary sequence of more than 2 kb upstream sequences of the cPR gene, containing several consensus hexamer progestin/glucocorticoid receptor-binding sites (PRE/GRE and putative Sp1 binding motifs, is discussed.

Amino Acid Sequence↗