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Biomedical subjects

M Atger

Publications and source records attributed to M Atger.

At least 19 recordsLinked to original sources

[Role of testicular biopsy in the investigation of a carcinoma in situ].

Carcinoma in situ (CIS) of the testis is recognized to be a precursor of cancer. Radiological examinations are not sufficient to improve the diagnosis. So the diagnosis is made by testicular biopsy. The indications are controlateral testis biopsy in man with testicular cancer and risk factors (cryptorchidism, dysgenetic gonads...) and extragonadic germ cell tumors. The authors review the risk factors. Chemotherapy is not sufficient to eradicate the CIS. A dose of 16 Gy of localized radiation is curative, excludes bilateral orchidectomy and preserves androgen function and azoospermic patient.

Biopsy

[Acute pyelo-ureteral obstruction by an intrasinusal intra- and para-pyelic cyst. Apropos of 3 cases].

Parapyelic cysts are not uncommon. There is usually no clinical expression of these cysts although development within the sinus can cause obstruction leading to acute nephretic colic. We observed two cases of intrasinus parapyelic cysts and another case of obstructive intrapyelic cyst. At ultrasonography, the only sign was hydronephrosis and a junction syndrome could not be eliminated. Intravenous pyelography demonstrated hydronephrosis and in one case a round intrapyelic mass. Computed tomography was required for diagnosis. Surgical exeresis was required due to the pain and compression damage to the parenchyma. This is a rare indication for surgical treatment of simple cysts of the kidney.

Acute Disease

[Orchidectomy in testicular cancer. Variant techniques and tactics].

Exploratory orchidotomy, generally leading to orchidectomy, is the first procedure performed whenever testicular cancer is suspected. The techniques and indications for wide orchidectomy have advanced since the time of Chevassu: radical orchidectomy with lymph node dissection via an inguinoiliolumbar incision is no longer performed, value of wide orchidectomy associated with radiotherapy or chemotherapy, place of enucleations in the case of solitary testis or synchronous bilateral lesions, and deferred orchidectomy after chemotherapy. The various techniques are reviewed and their indications are discussed.

Biopsy

[Diagnostic difficulties and value of partial surgery in multiple tumors of the kidney. Apropos of 4 cases].

Multiple renal tumors are rare. Ultrasonic and CT scan examinations will suspect the diagnosis in the majority of cases. With the histological diagnosis and its prognosis, the treatment may be watchful waiting, partial nephrectomy or radical nephrectomy. Partial nephrectomy is indicated in case of multiple tumor in a patient with solitary kidney or for bilateral tumors. Urinary fistulas or renal insufficiency are potential complications, but they are exceptional. Four cases are reported (oncocytoma, angiomyolipoma, papillary tumor and adenocarcinoma) to illustrate the difficulty of diagnosis with imaging and the surgical options.

Adenoma, Oxyphilic

Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5' non-coding regions.

The complete organization of the human luteinizing hormone-choriogonadotropin (LH/CG) receptor (LH/CGR) gene and the structure of 1591 bp of its 5' flanking region have been determined. This gene spans over 70 kbp and contains 11 exons. The first ten exons and part of the last exon encode the extracellular domain of the receptor while the transmembrane and intracellular domains are encoded by the remaining part of the last exon. The gene encodes a 701 amino acids long preprotein, contrary to a previous report of 699 amino acids. Primer extension experiments and polymerase chain reaction (PCR) mapping allowed definition of the transcription initiation site, which is located 1085 bp upstream from the initiation codon. The 5' non-coding region is thus unusually long. The promoter region which is different from the murine LH/CG receptor promoter, contains two putative TATA boxes at positions -34 and -47 and a CAAT box consensus sequence at position -89. A consensus sequence corresponding to a cAMP responsive element is found at position -697. Seven API consensus sequences are also found in the 5' flanking region of the gene. Southern blot experiments demonstrated an informative biallelic polymorphism within the human LH/CG receptor gene locus using BglII endonuclease. The cloning of the human LH/CGR gene and the determination of the organization and structure of its 5' flanking region allow the study of its hormonal, developmental and tissue-specific regulation. Primers and PCR conditions are described for the direct genomic sequencing of all the exons of the gene. This information should facilitate the study of pathological mutations of the receptor.

Amino Acid Sequence

[Pituitary glycoprotein hormone receptors].

Monoclonal antibodies have been raised against the porcine LH receptor and have allowed to clone the corresponding messenger RNA from testicular cells. The stricture of the LH receptor has been determined. It shows similarities but also differences with other G protein coupled receptors. Specially a large extracellular domain is specific of that new family of receptors. Variant forms of the LH receptor generated by alternative splicing and lacking transmembrane domain have been isolated. Immunochemical and immunocytochemical studies have been performed. Three different forms of the LH receptor are physiologically expressed: a mature 85kDa transmembrane species, a 68 kDa high mannose containing species corresponding to a precursor which accumulates inside the cells, and truncated 45-48kDa molecular weight species corresponding to the variant messenger RNAs identified during the cloning of the receptor. A novel zonation of the ovary has been described by immunocytochemical studies. Cross hybridization with the LH receptor clone allowed to isolate the related TSH receptor from human thyroid tissue. The human LH and FSH receptor genes have been localized to chromosome 2p21 and the TSH receptor gene to chromosome 14q31. The genes are very large (> 60 kbp) and have introns only within the 5' part encoding the extracellular domain of the receptor. Immunoelectron microscopic studies performed in Leydig cells and in stably transfected L cells have allowed to study intracellular traffic of the LH receptor. The same approach was used to study the transendothelial transfer of hCG in testicular microvasculature.

Animals

[LH receptors. A new family of G-protein receptors].

Monoclonal antibodies have been raised against porcine LH receptor and allowed to clone the corresponding messenger RNA from testicular cells. The structure of the LH receptor have been determined. It shows similarities but also differences to other G protein coupled receptors. In particular a large extracellular domain is specific for that family of receptors. Variants forms of the LH receptor generated by alternative splicing and lacking transmembrane domains have been isolated. Immunochemical and immunocytochemical studies have been performed. Three different forms of the LH receptor are physiologically expressed: a mature 85 kDa transmembrane species, a 68 kDa high mannose containing species corresponding to a precursor which accumulate inside the cells, and truncated 45-48 kDa molecular weight species corresponding to the variant messenger RNAs identified during the cloning of the receptor. A novel zonation of the ovary has been described by immunocytochemical studies. Cross hybridisation with the LH receptor clone allowed to isolate the related human TSH receptor from thyroïds. The human LH and FSH receptor genes have been localized to chromosome 2p21 and the TSH receptor gene to chromosome 14q31. The genes are very large and have introns only within their 5' part corresponding to the extracellular domain of the receptor.

Cloning, Molecular

The chromosomal localization of the human follicle-stimulating hormone receptor gene (FSHR) on 2p21-p16 is similar to that of the luteinizing hormone receptor gene.

Two cDNA probes (5' and 3' region) corresponding to the human follicle-stimulating hormone receptor gene (FSHR) were used for chromosomal localization by in situ hybridization. The localization obtained on chromosome 2p21-p16 is similar to that of the luteinizing hormone/choriogonadotropin (LH/CG) receptor gene.

Chromosome Mapping

[LH and TSH receptors. A new family of G protein-coupled receptors].

Monoclonal antibodies have been raised against porcine LH receptor and allowed to clone the corresponding messenger RNA from testicular cells. Cross hybridisation with the LH receptor clone allowed to isolate a clone corresponding to the human TSH receptor from thyroids. The structure of both receptors have been determined. They show similarities but also differences to other G protein coupled receptors. In particular a large extracellular domain is specific of that new family of receptors. Variant forms of the LH receptor lacking transmembrane domains have been isolated. The obtention of monoclonal antibodies against both receptors allowed immunochemical and immunocytochemical studies to be performed. The human LH receptor gene have been localized to chromosome 2p21 and TSH receptor gene to chromosome 14q31. The complete organisation of the human TSH receptor gene has been determined.

Animals

Origin of the high constitutive level of progesterone receptor in T47-D breast cancer cells.

The T47-D breast cancer cell line constitutively expresses high levels of progesterone receptor (PR). This does not appear to be related to an anomaly in the estrogen receptor (ER) as shown by cloning of the ER cDNA from T47-D cells and its insertion into the expression vector pKSV-10. When transfected into heterologous Cos-7 and L cells this receptor exerts a normal biological activity, stimulating the transcription of a reporter gene only in the presence of estrogen. Moreover, normal estrogen regulation of the transcription of the reporter gene was also observed in situ in T47-D cells. Southern blot experiments showed the presence of four copies of the progesterone receptor gene in T47-D cells. This was related to the existence of four copies of chromosome 11 in these cells. The most likely explanation of the anomalous regulation of progesterone receptor expression in T47-D cells is thus the presence of at least one copy of the PR gene bearing an anomaly in its regulatory region(s).

Animals

Cloning, sequencing and expression of human TSH receptor.

Complementary cDNA clones encoding the TSH (thyroid stimulatory hormone) receptor were isolated from a human thyroid lambda gt10 library using Iow stringency hybridization with LH/hCG (luteinizing hormone-human choriogonadotropic hormone) receptor probes. Sequencing of the clones showed a 764 amino acid open reading frame. The first 21 amino acids probably correspond to a signal peptide, the mature protein thus contains 743 amino acids (calculated molecular weight: 84,501 daltons). Its putative structure consists of a 394 amino acid extracellular domain, a 266 amino acid membrane spanning domain with 7 putative transmembrane segments and a 83 amino acid intracellular domain. A high degree of homology is observed with LH/hCG receptor suggesting the definition of a new subfamily of G-protein coupled receptors. Computer search showed the presence in the putative third intracellular loop of a motif resembling that described in the non receptor type protein tyrosine kinases (c-src, c-yes, c-fgr, etc...). RNA blots showed that the receptor messenger RNA consists of two major species of 4300 and 3900 nucleotides. The cDNA was inserted into an expression vector and after transfection into COS 7 cells it was shown to produce a functional TSH receptor.

Adenylyl Cyclases

Structural and functional studies of mammalian progesterone receptors.

During the past years there has been an improvement in our understanding of the molecular mechanism of action of the progesterone receptor (PR). This was due to the obtention of monoclonal antibodies against PR which allowed the first structural analyses and led to the cloning of the genes.

Animals