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P Grimaldi

Publications and source records attributed to P Grimaldi.

At least 37 records · Page 2Linked to original sources

Acyl-CoA synthetase mRNA expression is controlled by fibric-acid derivatives, feeding and liver proliferation.

Several enzymes of the beta-oxidation pathway have been shown to be induced after stimulation with peroxisomal proliferators, including several hypolipidemic drugs. We investigated the regulation of the long-chain-acyl-CoA synthetase (ACS) gene in the liver. Fenofibrate, a hypolipidemic drug and potent peroxisomal proliferator, induced ACS gene expression in several tissues. In liver, large increases in ACS mRNA levels and ACS activity were observed after fenofibrate administration. Adipose tissue ACS mRNA levels and ACS activity were also stimulated upon fibrate treatment but to a lesser extent in comparison with liver ACS mRNA. Kidney ACS mRNA was only weakly induced, except for the highest dose and the longest treatment period, where a strong induction was observed. In contrast to these tissues, heart ACS mRNA and ACS activity remained almost unchanged after fenofibrate treatment. These effects of fenofibrate could be reproduced by other fibrates such as clofibrate. In addition, it is demonstrated that both nutritional composition and liver proliferation trigger ACS gene expression in liver. Consequently, these data suggest that ACS is a highly regulated enzyme with a potentially important control function in lipid metabolism.

Adipose Tissue↗

Cloning of alpha 2 chain of type VI collagen and expression during mouse development.

We have previously described the molecular cloning of a cDNA probe which detects a 6 kb mRNA termed pOb24. pOb24 mRNA appeared to be a marker of the preadipose state both in vitro and in vivo. A pOb24 genomic fragment was isolated and used to screen cDNA libraries in order to isolate the full-length pOb24 cDNA and to identify the corresponding protein. The screening yielded a new cDNA clone which detected a 3.7 kb mRNA species in addition to the 6 kb mRNA species. Sequences at the 3' end of the 6 kb and 3.7 kb mRNAs indicate that both mRNAs are generated from the same gene through the use of two different polyadenylation sites. The protein encoded by the 3.7 kb mRNA appeared to be homologous to the human alpha 2 chain of type VI collagen (A2COL6). The expression of the A2COL6 gene was not confined to adipose tissue; mRNA species can be detected in ovaries, adrenal glands and lungs but not in liver and skeletal muscle. The expression appeared specific for initial phase(s) of cell differentiation since it is parallel to that of the MyoD1 gene during muscle embryogenesis in vivo. In the myogenic C2C12 cell line, the A2COL6 gene exhibited the same regulation as MyoD1 and myogenin genes. These results indicate that A2COL6 gene expression is a marker of the preadipose state, but may also be a marker of other differentiation programmes such as that of muscle.

Amino Acid Sequence↗

Direct evidence that the mouse sex-determining gene Sry is expressed in the somatic cells of male fetal gonads and in the germ cell line in the adult testis.

Reverse transcriptase polymerase chain reaction (RT-PCR) analysis shows that Sry mRNA is expressed in male fetal urogenital ridges from 12.5 day p.c. embryos, but not in enriched populations of primordial germ cells from the same embryos, indicating that Sry is expressed in the somatic cells of the embryonal gonad at the time of testis determination. We also show that, in the adult male mouse testis, Sry mRNA is expressed at high levels in meiotic and postmeiotic germ cells and, at much lower levels, also in Sertoli cells. Treatment with cyclic adenosine monophosphate (cAMP) analogs of cultured Sertoli cells from postnatal testis completely abolishes Sry mRNA expression.

Animals↗

Follicle-stimulating hormone induction of steel factor (SLF) mRNA in mouse Sertoli cells and stimulation of DNA synthesis in spermatogonia by soluble SLF.

Follicle-stimulating hormone (FSH) and its intracellular mediator, cAMP, increase the mRNA levels for the Steel factor (SLF, the c-kit ligand) in cultured primary mouse Sertoli cells. The inductive effect of cAMP is more evident in cultures from 13-day-old animals than in cultures from 18-day-old animals. Analysis through the polymerase chain reaction (PCR) indicates that (Bu)2cAMP or FSH treatment increases the levels of the mRNAs for both the potentially soluble form and the transmembrane form of SLF in cultured Sertoli cells. The ratio between mRNAs encoding the potentially soluble form and the transmembrane form of SLF increases during postnatal testis development, and it is higher in cultured Sertoli cells with respect to total testis, suggesting that, under the in vitro conditions, SLF could be produced by Sertoli cells mainly as a soluble factor. Soluble recombinant SLF stimulates, in a dose-dependent fashion, thymidine incorporation in cultures of isolated germ cell populations enriched in the mitotic stages (spermatogonia), independently of the presence of serum, whereas cAMP analogs have no effect. Autoradiographic analysis shows that SLF selectively stimulates DNA synthesis in type A spermatogonia.

Alternative Splicing↗

Identification of 3',5'-cyclic adenosine monophosphate-inducible nuclear factors binding to the human urokinase promoter in mouse Sertoli cells.

Transcription factors which recognize both the SV40 promoter and the proximal promoter region of the human urokinase-type plasminogen activator (h-uPA) gene are present in nuclear extracts from primary cultures of mouse Sertoli cells; prolonged (more than 12 h) (Bu)2cAMP stimulation of Sertoli cells induces the formation of different specific DNA-protein complexes. A discrete region in the h-uPA promoter, between -54 and -42, is essential for the formation of the cAMP-induced DNA-protein complexes. Mutation of the sequence between -54 and -42 abolishes the response to cAMP of the proximal h-uPA promoter in Sertoli cells. A protein, recognizing a sequence centered around the GC-box present between -48 and -43, is detected by Southwestern analysis, and it is clearly induced by (Bu)2cAMP stimulation. Interaction between this protein and a second factor, recognizing a purine-rich sequence between -53 and -46, partially overlapping the GC-box, is needed for the formation of the cAMP-induced DNA-protein complexes. A preformed complex between the cAMP-induced GC-box-binding factor and the second factor can be detected using nondenaturing conditions during Southwestern analysis.

Animals↗

Latest Medicare benefit: FQHC (Federally Qualified Health Center) services.

The Federally Qualified Health Center (FQHC) service benefit has been effective since Oct. 1, 1991, but the governing "interim final" regulations were not issued until June 12, 1992. Paul Grimaldi, PhD, details the requirements that must be met in order for a clinic or center to qualify for FQHC reimbursement.

Ambulatory Care Facilities↗

Molecular dynamics study of the conformational behavior of a representative elastin building block: Boc-Gly-Val-Gly-Gly-Leu-OMe.

The conformational behavior of the synthetic peptide, Boc-Gly-Val-Gly-Gly-Leu-OMe, containing the X-Gly-Gly and Gly-Gly-X (X = Val or Leu) repeating sequences and constituting a fragment of elastin was investigated by molecular mechanics and molecular dynamics (MD) simulation. The results suggest that, irrespective of the approximations used, the molecule shows a manifold of low energy conformations characterized by gamma-turns and type II beta-turns. Furthermore, MD simulations point out a conformational floppiness due to very low barriers between different conformations. Experimental CD measurements in a virtually apolar medium (dioxane--epsilon = 2.209), which better mimics the vacuum conditions of the simulation, support the theoretical results. The general emerging picture, indicating the molecule as characterized by a combination of flexibility with conformational preferences, is in agreement with previous experimental findings and enriches of new aspects the description of the microscopic behavior of this molecule suggesting more detailed interpretation of previous data.

Amino Acid Sequence↗

PPS update.

Explore the source record for details and available documents.

Capital Expenditures↗

Cellular and molecular aspects of adipose tissue development.

Both in animals and humans, before or after birth, angiogenesis appears to be closely coordinated in time and space with the formation of fat cell clusters. Monobutyrin, a novel fat-specific angiogenesis factor, may play a role in this process. The potential to acquire new fat cells appears to be permanent throughout life in both animals and humans, as revealed by in vitro experiments. Considerable evidence now supports the view that BAT and WAT are distinct organs; in addition, the existence of distinct BAT precursor cells is demonstrated by their unique ability to express the UCP gene. In bovine and ovine, the transformation of BAT into WAT is strongly suggested by the rapid disappearance after birth of UCP from the various BAT depots. Despite the initial cell heterogeneity of the stromal-vascular fraction, cultured stromal-vascular cells of adipose tissue are adipose precursor cells that show varying capacities for replication and differentiation, according to age and fat depot. Studies of adipose cell differentiation in vitro correspond to the sequence: adipoblast (unipotential cells)----commitment preadipose cell (preadipocyte)----terminal differentiation immature adipose cell----terminal differentiation mature adipose cell (adipocyte). Cell commitment is triggered by growth arrest and characterized by the expression of early markers (A2COL6/pOb24; clone 5; LPL), whereas only terminal differentiation of preadipocytes requires the presence of various hormones. Multiple signaling pathways have been characterized and shown to cooperate in the process of terminal differentiation. The concept that adipose cells behave as secretory cells is now emerging from in vitro data, since secretion of various proteins (LPL, adipsin, CETP) and important metabolites (fatty acids, monobutyrin, androgens, estrogens, prostaglandins) takes place both constitutively and upon hormonal stimulation. This suggests that adipose tissue participates more directly than previously thought in metabolic activities and energy balance.

Adipose Tissue↗

Changes in Medicare capital PPS rates and rules.

Author Grimaldi discusses recent changes in Medicare's capital prospective payment system (PPS) regulations, published in the Federal Register, September 1992, as well as major changes in operating cost guidelines that affect capital payments. Policy interpretations that the Health Care Financing Administration (HCFA) has issued in the past year are reviewed, and changes made to the Medicare cost report in order to accommodate capital PPS are summarized schedule by schedule.

Capital Expenditures↗