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A Daga

Publications and source records attributed to A Daga.

30 records · Page 2Linked to original sources
PubMed1993

The homeotic gene products in the control of cell differentiation and proliferation.

Embryo development is controlled by a successive series of genes that provide each cell in the growing embryo with precise position information. Knowledge of these genes is known most completely from Drosophila, where a simple initial pattern generated by maternal effect genes is gradually segmented by the sequential transient expression of three successive series of genes: the gap genes, the pair-rule genes, and the segment polarity genes. Superimposing their action on the preexisting segments, these homeotic genes cause unique and often very distinctive patterns of differentiation for different segments. In humans, about 40 homeotic genes have been identified and are grouped into four clusters on chromosomes 2, 7, 12, and 17, whose organization reflects their spatial and temporal expression. Several homeotic genes have been found expressed not only in embryonic tissues, but also in adult tissues, most notably in the hematopoietic lineage, and also in tumors, especially leukemia, teratocarcinoma, and neuroblastoma, wherein their expression pattern is modified in a complex manner by retinoic acid. The target genes of the transcription factors encoded by the homeotic genes are largely unknown, but recent reports indicate that they may regulate the expression of adhesion molecules on the membrane and the production of components of the extracellular matrix. Abnormal expression of these genes can therefore affect not only cell proliferation, but also the spread of cells to aberrant locations.

Animals↗
PubMed1992

Differential DNA binding properties of three human homeodomain proteins.

The products of three human homeobox containing (HOX) genes, 2C, 3C and 4B, were produced in insect cells using the Baculovirus expression system and purified to near homogeneity. In this system we observed that the DNA binding forms of the three proteins are not glycosylated. HOX 3C and 4B are phosphorylated in insect cells, while HOX 2C is not. The three HOX proteins bind to a DNA sequence known to be a target site for Antennapedia protein with a very similar affinity (Kd = 1-2 x 10(-9) M). We then measured their binding properties to four human sequences present in the HOX 3D, 4C, 1C and 4B promoters. Two of these sequences have been reported to be binding sites for HOX proteins. HOX 2C, 3C and 4B behaved quite differently, showing low affinity for promoters of genes located upstream from their own gene in the HOX clusters and a higher affinity for regulatory sequences of their own gene and downstream HOX genes.

Animals↗
PubMed1992

MELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts.

The pathogenetic mechanism of the mitochondrial tRNA(LeuUUR) gene mutation responsible for the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome was investigated in transformants obtained by transfer of mitochondria from three genetically unrelated MELAS patients into human mitochondrial DNA (mtDNA)-less (rho 0) cells. Marked defects in mitochondrial protein synthesis and respiratory activity were observed in transformants containing virtually pure mutant mtDNA, as compared to the parent of the rho 0 cells (the 143B cell line) or to transformants containing exclusively wild-type mtDNA, derived from one of the patients or a maternally related asymptomatic individual. A striking protective effect against the mutation was exerted in the transformants by levels of residual wild-type mtDNA above 6%. The MELAS mutation occurs within the mtDNA binding site for a protein factor (mTERF) that promotes termination of transcription at the 16S rRNA/tRNA(LeuUUR) gene boundary. A marked decrease in affinity of purified mTERF for the mutant target sequence was observed in in vitro assays. By contrast, RNA transfer hybridization experiments failed to show any significant change in the steady-state amounts of the two rRNA species, encoded upstream of the termination site, and of the mRNAs encoded downstream, in the transformants carrying the MELAS mutation.

Acidosis, Lactic↗
PubMed1990

Use of three DNA polymorphisms of the LDL receptor gene in the diagnosis of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant metabolic disorder caused by several different mutations in the low density lipoprotein (LDL) receptor gene. This large number of different mutations, often undetectable in Southern blotting, makes it impossible directly to diagnose the disease. However, restriction fragment length polymorphisms (RFLPs) can be used to follow the inheritance of the defective gene in FH families. In the present study, we report the use of three RFLPs, detected by PvuII, ApaLI and AvaII restriction enzymes, to determine the haplotypes of normal and defective LDL receptor genes in 61 families with FH and in 128 normal individuals. Two of the nine haplotypes were significantly more often associated with the affected genes, whereas one was significantly less frequent. Although none of the associations was strong enough to allow diagnosis in individuals, it was possible, using the three RFLPs, to identify the haplotype of the affected gene in 57 families and to carry out unequivocal diagnosis in 67% of the cases. In four families, PvuII and AvaII detected an abnormal fragment co-segregating with the disease, thus increasing the percentage of diagnosis to 73.4% of the cases.

Alleles↗
PubMed1989

Endocrine, metabolic, and clinical effects of gestrinone in women with endometriosis.

The effect of oral gestrinone, 2.5 mg twice weekly for 6 months, was studied in 11 women with mild or moderate endometriosis laparoscopically confirmed. The mean laparoscopic score decreased from 17.18 to 9.09 (P greater than 0.005). Painful symptoms were relieved in all patients within 2 months from start of therapy. Gonadotropins, prolactin (PRL) 17 beta-estradiol (17 beta-E2), estrone (E1), progesterone (P), androstenedione (A), and dehydroepiandrosterone sulfate (DHEA-S) remained in the follicular phase range. Total testosterone (TT) and sex hormone-binding globulin (SHBG) decreased, whereas free testosterone (FT) slightly increased. Metabolic studies showed a decrease of total triglycerides, very low-density lipoprotein (VLDL) triglycerides, and high-density lipoprotein (HDL) and VLDL cholesterol, parallel to the decrease of associated apoproteins. Low-density lipoprotein cholesterol and apoprotein B increased during therapy. The results suggest that gestrinone possesses antiestrogenic, androgenic, and progestigenic effects at therapeutic dosages both by acting on central and peripheral steroid receptors. For its efficacy and good tolerance, gestrinone may be considered an option for treating endometriosis.

Adult↗
PubMed1988

Effect of a single daily dose treatment of fenofibrate on plasma lipoproteins in hyperlipoproteinaemia IIb.

The safety and efficacy of a single daily dose of fenofibrate (200 mg) have been evaluated in 12 Type IIB hyperlipidaemic patients in a three-month study. At the same time the pharmacokinetics was studied to check whether this new dosage schedule would give a therapeutic plasma levels of fenofibrate. At the single daily dose of 200 mg, fenofibrate was highly effective, very well tolerated, and it reached therapeutic plasma levels without accumulation. It appears that fenofibrate can usefully be employed at this dosage in hyperlipidaemia, especially since patient compliance is better when only one daily dose need be taken.

Adult↗
PubMed1986

Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children.

Following a brief outline of current knowledge concerning atherosclerosis and its treatment, the authors describe the results obtained by treating with pantethine (900-1200 mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering from hypercholesterolemia alone or associated with hypertriglyceridemia (types IIa and IIb of Fredrickson's classification). Pantethine treatment produced significant reduction of the better known risk factors (total cholesterol, LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol (signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion of these results and of the possible role of pantethine in the treatment of hyperlipoproteinemia, in view of its perfect tolerability and demonstrated therapeutic effectiveness.

Adolescent↗
PubMedDate not supplied

Microenvironment and stem properties of bone marrow-derived mesenchymal cells.

Adult stem cells are self-renewing, pluripotent, and able to repopulate the tissue in which they reside. Cells endowed with these properties have been isolated from several tissues and an increasing number of reports provide evidence of their ability, following transplantation, to engraft host tissues other than those of their origin. In this setting, interest in the well-documented capacity of bone marrow stromal cells to undergo multilineage differentiation is growing. Neural and cardiomyogenic lineages have recently been proposed as additional differentiative pathways of these cells. However, culture conditions and inductive molecules can alter the behavior of bone marrow stromal cells and the microenvironment is critical for proper in vivo delivery. The maintenance of their stem properties and the possibility of reprogramming their commitment is a field of primary interest given the potential use of these cells in regenerative medicine. We discuss here how the microenvironmental cues, and the growth factors that physiologically govern commitment and subsequent differentiation, influence the properties of bone marrow stromal cells and modulate their engraftment into host tissues.

Bone Marrow Cells↗
PubMedDate not supplied

Pvu II polymorphism of low density lipoprotein receptor gene and familial hypercholesterolemia. Study of Italians.

Familial hypercholesterolemia is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low density lipoprotein (LDL) level. It has been demonstrated that the disease is caused by several different mutations in the LDL receptor gene. Although early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infarction, the available techniques for determining the number of the functional LDL receptor molecules are not sufficiently accurate. The recent isolation of the LDL receptor gene now makes it possible to use restriction fragment length polymorphisms to study the inheritance of the defective allele in families with familial hypercholesterolemia. In the present study, we report the use of a Pvu II restriction fragment length polymorphism to follow the inheritance of familial hypercholesterolemia in a total of 79 patients from 37 different families. This restriction fragment length polymorphism allowed unequivocal diagnosis in 32.5% of the cases. Furthermore, in the Italians studied, the absence of a polymorphic Pvu II cutting site (P1 allele) was found to be strongly associated with familial hypercholesterolemia.

Adolescent↗