Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “somatic evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed2002

Dental microstructure and life history in subfossil Malagasy lemurs.

When compared with their recently extinct relatives, living lemurs represent a mere fraction of a broad radiation that occupied unique niches in the recent past. Among living lemurs, indrids exhibit the fastest rates of dental development. This dental precocity is tightly correlated with rapid pace of postnatal dental eruption, early replacement of the deciduous teeth, high dental endowment at weaning, and relatively slow somatic growth. This pattern is in stark contrast to that seen in extant lemurids, where somatic development is highly accelerated and dental development is relatively slow. We report on the pace of dental development in one species of palaeopropithecid, the sister group to extant indrids. Like much smaller modern indrids, the chimpanzee-sized Palaeopropithecus ingens was dentally precocious at birth as evidenced by the advanced state of molar crown formation. This finding implies a pattern characteristic of Propithecus and other indrids-rapid dental development despite relatively prolonged gestation. Gestation length in this one species of subfossil lemur was likely greater than 9 months. Our results demonstrate that large body size in primates does not preclude exceedingly rapid dental development.

Animals↗
PubMed1989

A comprehensive genetic map of murine chromosome 11 reveals extensive linkage conservation between mouse and human.

Interspecific backcross animals from a cross between C57BL/6J and Mus spretus mice were used to generate a comprehensive linkage map of mouse chromosome 11. The relative map positions of genes previously assigned to mouse chromosome 11 by somatic cell hybrid or genetic backcross analysis were determined (Erbb, Rel, 11-3, Csfgm, Trp53-1, Evi-2, Erba, Erbb-2, Csfg, Myhs, Cola-1, Myla, Hox-2 and Pkca). We also analyzed genes that we suspected would map to chromosome 11 by virtue of their location in human chromosomes and the known linkage homologies that exist between murine chromosome 11 and human chromosomes (Mpo, Ngfr, Pdgfr and Fms). Two of the latter genes, Mpo and Ngfr, mapped to mouse chromosome 11. Both genes also mapped to human chromosome 17, extending the degree of linkage conservation observed between human chromosome 17 and mouse chromosome 11. Pdgfr and Fms, which are closely linked to II-3 and Csfgm in humans on chromosome 5, mapped to mouse chromosome 18 rather than mouse chromosome 11, thereby defining yet another conserved linkage group between human and mouse chromosomes. The mouse chromosome 11 linkage map generated in these studies substantially extends the framework for identifying homologous genes in the mouse that are involved in human disease, for elucidating the genes responsible for several mouse mutations, and for gaining insights into chromosome evolution and genome organization.

Animals↗
PubMedDate not supplied

Newer concepts of the autonomic system's role derived from reductionist and behavioral studies of various animal species.

The evolution of newer concepts, many from old precursors, are elaborated. Among the bases for new thought has been the realization that all body tissues receive autonomic innervation and that this system affects all functions. It is involved in the minutia or reactions studied by their reductionists and in activity of the total organism studied by behaviorists. Newer knowledge suggests that the system's functions can be subdivided into 2 major categories: (1) a role in basic metabolic or vegetative functions. There are 3 realms of such involvement: in energy storage and release; in control of endocrine and neuroendocrine secretions; and in control of exocrine secretion and thus intake, conservation or loss and transformation of energy. The hypothalamus is most highly involved in these autonomic system functions; (2) a role in behavior. The hypothalamus is also highly involved, especially in alerting and defense reactions, concepts relating to Cannon's ideas of emergency function and Selye's concepts of stress. It can be said that the normal, phasic functions of the autonomic system and its involvement in organ and body reactivity are controlled in parallel with the regulation of somatic performances. The several newer interpretative ideas originating from studies of reflexes, reflex patterns and sequences, and of general behavior are the integrative role, the supportive role, the modulatory and finally the anticipatory or determinative role in behavior. The similarity of the role of the autonomic nervous system function in all species, from birds to man, has caught the attention of investigators. This rather than the specializations of the system that are appropriate to the peculiar characteristics of individual species has been emphasized; but species specializations do exist and these should be worthy of future investigation. New concepts of the system's role are evolving from old ideas and new discoveries. Newer concepts of transmitter genesis and tissue receptors are developing that add more detail to our major channels of thought concerning the autonomic system's function. There is a new realization of the system's involvement in pain. Its' directives affect and integrate organ and tissue activity; it determines behavior and expresses the sympathy and judgements of man.

Aging↗
PubMed1998

Zebrafish hox genes: genomic organization and modified colinear expression patterns in the trunk.

The Hox genes are implicated in conferring regional identity to the anteroposterior axis of the developing embryo. We have characterized the organization and expression of hox genes in the teleost zebrafish (Danio rerio), and compared our findings with those made for the tetrapod vertebrates. We have isolated 32 zebrafish hox genes, primarily via 3'RACE-PCR, and analyzed their linkage relationships using somatic cell hybrids. We find that in comparison to the tetrapods, zebrafish has several additional hox genes, both within and beyond the expected 4 hox clusters (A-D). For example, we have isolated a member of hox paralogue group 8 lying on the hoxa cluster, and a member of hox paralogue group 10 lying on the b cluster, no equivalent genes have been reported for mouse or human. Beyond the 4 clusters (A-D) we have isolated a further 3 hox genes (the hoxx and y genes), which according to their sequence homologies lie in paralogue groups 4, 6, and 9. The hoxx4 and hoxx9 genes occur on the same set of hybrid chromosomes, hinting at the possibility of an additional hox cluster for the zebrafish. Similar to their tetrapod counterparts, zebrafish hox genes (including those with no direct tetrapod equivalent) demonstrate colinear expression along the anteroposterior (AP) axis of the embryo. However, in comparison to the tetrapods, anterior hox expression limits are compacted over a short AP region; some members of adjacent paralogue groups have equivalent limits. It has been proposed that during vertebrate evolution, the anterior limits of Hox gene expression have become dispersed along the AP axis allowing the genes to take on novel patterning roles and thus leading to increased axial complexity. In the teleost zebrafish, axial organization is relatively simple in comparison to that of the tetrapod vertebrates; this may be reflected by the less dispersed expression domains of the zebrafish hox genes.

Amino Acid Sequence↗
PubMed2004

Dimorphecolic acid is synthesized by the coordinate activities of two divergent Delta12-oleic acid desaturases.

Dimorphecolic acid (9-OH-18:2Delta(10)(trans)(,12)(trans)) is the major fatty acid of seeds of Dimorphotheca species. This fatty acid contains structural features that are not typically found in plant fatty acids, including a C-9 hydroxyl group, Delta(10),Delta(12)-conjugated double bonds, and trans-Delta(12) unsaturation. Expressed sequence tag analysis was conducted to determine the biosynthetic origin of dimorphecolic acid. cDNAs for two divergent forms of Delta(12)-oleic acid desaturase, designated DsFAD2-1 and Ds-FAD2-2, were identified among expressed sequence tags generated from developing Dimorphotheca sinuata seeds. Expression of DsFAD2-1 in Saccharomyces cerevisiae and soybean somatic embryos resulted in the accumulation of the trans-Delta(12) isomer of linoleic acid (18: 2Delta(9)(cis)(,12)(trans)) rather than the more typical cis-Delta(12) isomer. When co-expressed with DsFAD2-1 in soybean embryos or yeast, DsFAD2-2 converted 18:2Delta(9)(cis)(,12)(trans) into dimorphecolic acid. When DsFAD2-2 was expressed alone in soybean embryos or together with a typical cis-Delta(12)-oleic acid desaturase in yeast, trace amounts of the cis-Delta(12) isomer of dimorphecolic acid (9-OH-18:2Delta(10)(trans,)(12)(cis)) were formed from DsFAD2-2 activity with cis-Delta(12)-linoleic acid [corrected]. These results indicate that DsFAD2-2 catalyzes the conversion of the Delta(9) double bond of linoleic acid into a C-9 hydroxyl group and Delta(10)(trans) double bond and displays a substrate preference for the trans-Delta(12), rather than the cis-Delta(12), isomer of linoleic acid. Overall these data are consistent with a biosynthetic pathway of dimorphecolic acid involving the concerted activities of DsFAD2-1 and DsFAD2-2. The evolution of two divergent Delta(12)-oleic acid desaturases for the biosynthesis of an unusual fatty acid is unprecedented in plants.

Calendula↗
PubMedDate not supplied

Aging Liver. A review.

Aging is characterized by a progressive decline of cellular functions. The aging liver appears to preserve its function relatively well. Aging is associated in human liver with morphological changes such as decrease in size attributable to decreased hepatic blood flow. Ultrastructural analysis of the human liver has revealed that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver. Endogenous free radicals are generated within mitochondria and suspected to cause severe injury to mitochondrial DNA. This damaged DNA accumulates with aging. In addition, polyunsaturated fatty acids, highly sensitive to ROS, decrease in liver mitochondria from human centenarians, a feature acquired during evolution as a protective mechanism to favor longevity. Diet is considered the main environmental factor having effect on lifespan. It has a major impact on aging liver, the central metabolic organ of the body. The ubiquitin proteolytic pathway in the liver serves to destroy many proteins, among them p21 which is encoded by abundant mRNA in senescent cells, can inhibit cell proliferation and favors DNA repair. Drug therapy in the elderly may be complicated by several factors such as decline in body weight, renal function, liver mass and hepatic blood flow, making adverse drug reactions more frequent. Hepatic drug metabolism is mainly mediated by the cytochrome P(450 )system and drug interactions in the elderly are likely related to the progressive decline of this system after the fifth decade of life and another decrease in individuals aged >70. Antihypertensive therapy in the elderly depends upon either hepatic or renal function and should be adjusted accordingly. Finally, telomerases are the biological clocks of replicative lifespan. Shortening of telomeric ends of chromosomes correlates with aging and decline in the replicative potential of the cell: replicative senescence. Telomere DNA of human somatic cells shortens during each cell division thus leading to a finite proliferation. Transfection of the telomerase reverse transcriptase gene results in elongation of telomeres and extension of lifespan. This also applies to humans. Replicative senescence in human cells evolved as a mechanism to protect them from continuous divisions leading to multiple mutations. Longer-lived species such as humans had to develop replicative senescence to ensure that they would have the increased protection that their longevity necessitates.

Aging↗
PubMedDate not supplied

[Structural characteristics of lysine-rich histone from the sperm of a mollusk Anodonta piscinalis].

Sperm of freshwater bivalve mollusk Anodonta piscinalis was found to contain two fractions of lysine-rich histone: somatic histone H1 and sperm-specific protamine-like histone, named Hp. A detailed analysis of H1 and Hp structure was carried out by means of N-bromosuccinimide, chymotrypsin and pepsin cleavage followed by determination of the lysine residue number, positive charge and molecular length of obtained fragments by the method of incomplete succinylation. It has been shown, that Anodonta histone H1, like the avian histone H5, contains 3 tyrosine residues in the central hydrophobic domain of the molecule. Histone Hp contains 5 tyrosine residues, 3 of which are localized in the hydrophobic domain, while the rest two--in the COOH-terminal part of the molecule, characterized by a strong positive charge. Such unusual disposition of tyrosine residues in the lysine-rich histone has been found for the first time. All the regions of histone Hp molecule contain a great number of arginine residues. The only phenylalanine residue is localised approximately in the middle of the polypeptide chain for both H1 and Hp molecules. On the basis of structure homology between histones H1 and Hp the origin of Hp from H1 in the course of evolution is proposed.

Amino Acid Sequence↗
PubMed2000

Paroxysmal nocturnal haemoglobinuria: a replacement of haematopoietic tissue?

Acquired somatic mutations of the PIG-A gene lead to deficient expression of glycosyl-phosphatidyl-inositol-anchored proteins (GPI-AP) by haematopoietic cells and play a causative role in the pathogenesis of paroxysmal nocturnal haemoglobinuria (PNH). However, PIG-A mutations do not explain how the defective PNH clone can expand. It was hypothesized that a selection process conferring a relative advantage to the GPI-AP-deficient population is required. Since GPI-AP-deficient cells are also detectable in a substantial proportion of patients with otherwise typical aplastic anaemia (AA), the mechanisms inducing bone marrow failure might selectively spare the GPI-deficient cells. In order to examine the growth characteristics of GPI-AP-deficient cells in more detail, we performed repeated analyses of GPI-AP expression on peripheral blood cells in 41 patients with AA. We observed four patterns of the course of GPI-AP-deficient populations: (1) 13 patients showed normal expression of GPI-AP in the first analysis and in at least two follow-up studies at a median time of 709 days after the first analysis. (2) Secondary evolution of a GPI-AP-deficient population was a rare event. Only 4 patients with initially normal GPI-AP expression developed a GPI-AP-deficient population during follow up after immunosuppressive treatment. (3) Persistence of GPI-AP-deficient cells was observed in 16 patients during a median follow-up time of 774 days. However, in some patients, the size of the GPI-AP-deficient population increased substantially. (4) Disappearance of a GPI-AP-deficient population was observed in 8 patients. The time course of GPI-AP expression in relation to the treatment suggests that therapeutic interventions might modulate the ratio of normal versus GPI-AP-deficient haematopoiesis. Overall, these data argue against an 'absolute growth advantage' of GPI-AP-deficient cells. Our data are consistent with the hypothesis that haematopoietic failure caused by damage to normal haematopoiesis allows the outgrowth of a GPI-AP-deficient population. Thus, in at least some patients GPI-AP-deficient cells might pre-exist at a very low percentage and replace haematopoiesis after an insult to the normal cells.

Anemia, Aplastic↗
PubMed1999

Quantitative chromosome map of the polyploid Saccharum spontaneum by multicolor fluorescence in situ hybridization and imaging methods.

Somatic chromosomes of a wild relative of sugarcane (Saccharum spontaneum L.) anther culture-derived clone (AP 85-361, 2n = 32) were identified and characterized by computer-aided imaging technology and molecular cytological methods. The presence of four satellite chromosomes and four nearly identical chromosome sets suggests that the clone is a tetrahaploid with the basic number x = 8. A quantitative chromosome map, or idiogram, was developed using image analysis of the condensation pattern (CP) at the prometaphase stage of somatic chromosomes. The 45S and 5S ribosomal RNA gene (rDNA) loci were simultaneously visualized by multi-color fluorescence in situ hybridization (McFISH) and precisely localized to the regions of 3p3.1 and 6q1.3 on the idiogram. The simultaneous visualization of two sets of four ribosomal RNA genes confirms tetraploidy of this clone. This conclusion is consistent with results of molecular marker mapping. The quantitative chromosome map produced will become the foundation for genome analyses based on chromosome identity and structure. Previously impossible identification of small chromosomes and untestable hypotheses about the polyploid nature of plants can now be settled with these two approaches of quantitative karyotyping and FISH.

Chromosomes↗
PubMed1991

Assignment of the human small inducible cytokine A2 gene, SCYA2 (encoding JE or MCP-1), to 17q11.2-12: evolutionary relatedness of cytokines clustered at the same locus.

The JE gene, cloned from platelet-derived growth factor (PDGF)-treated mouse 3T3 cells, was the first PDGF-inducible gene to be described. Its human homolog (gene name "small inducible cytokine A2" [SCYA2]) encodes the monocyte specific chemotactic factor MCP-1 (or MCAF) which is structurally related to a recently described family of cytokines. By a combination of in situ hybridization and study of somatic cell hybrids, we have assigned the human SCYA2 gene to 17q11.2-12, the locus to which other members of this family have been mapped. We have also reconstructed a phylogenetic tree relating the members of this family to each other and to their murine homologs which suggests that these genes arose by duplication and divergence prior to the murine/human divergence. Four of the five members of this subfamily have now been assigned to the same locus (and the fifth to chromosome 17), while several of the members of a related gene family have been assigned to 4q. We propose that the two subfamilies be designated the 17q and 4q subfamilies.

Amino Acid Sequence↗
PubMed1986

Gene conversion in a cytochrome P-450 gene family.

The mRNAs encoding the two major phenobarbital-inducible forms of cytochrome P-450 of rat liver, P-450b and P-450e, are remarkably similar (98% homologous) in nucleotide sequence, but the distribution of differences within them is not random. While the 5' halves (approximately equal to 1 kilobase) appear to be identical, there are 36 divergent residues in the remaining sequences of the two mRNAs, with 14 differences residing in two short highly divergent segments, which in the P-450e gene are located within exon 7. DNA sequence analysis of portions of a number of P-450b/e-related genes provides strong evidence that at least one of the short divergent segments is the result of a recent gene conversion event between an ancestor to the cytochrome P-450e gene and a related donor P-450 gene of unknown function. The sequence data also suggest that extensive gene conversion has occurred within all the members of this gene family in the region including exons 7 and 8 and the intron between them, with a resultant homogenization of those sequences relative to other portions of the genes. Genomic Southern blotting analysis demonstrates that the presence of an apparent "constant" region in the 5' halves of the P-450b and P-450e mRNAs does not reflect a rearrangement in somatic cells of a germ-line DNA configuration. It is therefore proposed that it, too, is a consequence of a very recent gene conversion event between ancestors of the genes encoding both proteins or of an unequal crossing-over between them. On the basis of these and other data we propose that gene conversion represents an important evolutionary mechanism for the generation of related cytochrome P-450 isozymes in which regions of extraordinary sequence similarity and dissimilarity are intermixed. The gene conversion mechanism would account for some of the overlaps in substrate specificities of distantly related P-450s as well as for substantial differences in catalytic properties between closely related members of the same P-450 protein family.

Animals↗
PubMed1976

[Patterns characterizing different levels of animal organization].

The article deals with features of the regularities characterizing different levels of organization of the animal body. The cell is not only an integrated but also indivisible organic integrity which is due to the interaction of the nucleus and cytoplasm determining all sides of its vital activity. From this viewpoint the results of experiments on transplantation of the embryo cell nucleus into an enucleated egg of amphibia and the data on somatic hybridization are estimated. All processes of the cell life, their growth, multiplication and differentiation develop within the tissue system and are determined by the regularities of its development. The integrated system of the organism of a multicellular animal unites all the forms of integration of multi-step systemic pattern at different organization levels. Among different categories the systems of tissues and their interaction within the organ are most integrated. The regularities of the tissue development can not be brough to the regularities of the development of the anatomical structure of organs. The integration of cell elements in a tissue system and intertissue relations is the basis of all forms of interdependence in the cell development and the organism structure.

Animal Population Groups↗
PubMed1990

Clonal analysis of the cell lineages in the male flower of maize.

The cell lineages in the male flower of maize were characterized using X-rays and transposable elements to produce clonal sectors differing in anthocyanin pigmentation. Less than 50% of the somatic tassel mutations (caused by reversion of unstable color mutations) that were visible on the anther wall were sexually transmitted by the male gametes, unless the sectors were larger than half the tassel circumference. This result is explained by showing that: (a) both the outer (LI) and inner (LII) lineages of the shoot apical meristem form a cell layer in the bilayered anther wall, and that anther pigmentation can be derived from either cell layer; and that (b) the male germ cells are derived almost exclusively from the LII. Therefore, while reversion events in either the LI or LII are visible on the anther, only the LII events are heritable. Reversion events that occur prior to the organization of the shoot apical meristem however, produce large (usually more than one-half tassel) sectors that include both the outer and inner lineages. In contrast to the high level of cell layer invasion previously reported during leaf development, during anther development less than 10(-3) cells in the LI invade the LII to form male gametes. The strong correlation between cell lineage and cell fate in the maize anther has implications for studies on plant evolution and the genetic improvement of cereals by DNA transformation.

Anthocyanins↗
PubMed2005

New insights into alternative mechanisms of immune receptor diversification.

The clonal commitment, selection, and expansion of B and T lymphocytes expressing diversified receptors provide the underlying basis for the jawed vertebrates adaptive immune response. At the core of this process is the rearrangement and somatic modification of segmental genetic elements that encode the constituent components of immunoglobulins and T-cell antigen receptors. No evidence has been found for a similar mechanism outside of jawed vertebrates; however, invertebrates and jawless vertebrates are subjected to continuous exposure to pathogenic bacteria, viruses, and parasites. The invertebrates and jawless vertebrates as well as jawed vertebrates all encode a variety of mediators of innate immunity. Several reports of extensive germline diversification of conventional innate receptors, as well as molecules that resemble innate receptors but undergo germline and somatic modification, have been made recently. The range of such molecules, which include the fibrinogen-related proteins (FREPs) in a mollusc, variable region-containing chitin-binding proteins (VCBPs) in a cephalochordate, variable lymphocyte receptors (VLRs) in jawless vertebrates, and novel immune-type receptors (NITRs) in bony fish, encompasses both the immunoglobulin gene superfamily (IgSF) and leucine-rich repeat (LRR) proteins. Although these molecules vary markedly in form and likely in function, growing evidence suggests that they participate in various types of host defense and thereby represent significant alternatives to current paradigms of innate and adaptive immune receptors. Unusual genetic mechanisms for diversifying recognition proteins may be a widespread characteristic of animal immunity.

Adaptation, Physiological↗
PubMed1999

Junctional diversity in Xenopus immunoglobulin light chains.

Xenopus cDNA sequences encoding the homolog of mammalian kappa (kappa) light (L) chains were isolated from isogenic tadpole and adult individuals to investigate whether there existed stage-specific immunoglobulin L chain expression and somatic diversification. In the course of these studies rearrangements to a sixth J(L) gene segment and a pseudogene (J(L)psi) were found, and it is suggested that the order of these gene segments with respect to the L chain constant (C) region exon is: J(L)6-J(L)1-J(L)2-J(L)3-J(L)4-J(L)5-J(L)psi-C(L). The cDNA junctional diversity was analyzed; few N and P regions were found and almost all the CDR3 were 9 codons in length. There were restricted patterns of recombination site resolution, and this is attributed to some constraint in JL coding end processing.

Animals↗
PubMed1995

Mechanisms involved in the immortalization of mammalian cells by ionizing radiation and chemical carcinogens.

Immortalization is a prerequisite for the clonal evolution and malignant transformation of normal mammalian cells in culture. In order to gain a mechanistic insight into the genetics of carcinogen-induced cellular immortality, a cell culture assay has been developed based on the use of freshly explanted Syrian hamster dermal (SHD) fibroblasts. The relative efficacies of a variety of chemical and physical carcinogens at immortalizing SHD cells (against a zero background of spontaneous immortalization) were compared. Ionizing radiation and nickel chloride appeared to be more effective as immortalizing agents than powerful point mutagens, suggesting (but not proving) that clastogenic damage may be more significant in the immortalization process than point mutation. Frequencies of induced immortality (10(-6)-10(-7)/treated cell) were arguably consistent with a direct mutational mechanism involving a single genetic target. However, detailed cytogenetic characterization of a panel of newly immortalized cell lines revealed no non-random chromosomal alterations in the cells at the level of G-banding. Furthermore, additional experiments with the SHD system have provided confirmatory evidence that immortalization can occur as an indirect consequence of carcinogen exposure following an induced high frequency change in the treated population, rather than through direct targeted mutagenesis. Previous somatic cell genetic studies have suggested the possibility that a target gene for immortalization exists on the human and Chinese hamster X chromosomes. Here we provide strong evidence that the normal SHD X chromosome displays powerful senescence-inducing properties when introduced, by microcell transfer, into newly immortalized SHD recipients. These results suggest that induction of the immortal phenotype in SHD cells by carcinogens results primarily from functional inactivation of a senescence gene which may be X-linked. One possible mechanism for senescence gene inactivation consistent with our observations is through a sub-microscopic interstitial genetic deletion. However, the considerable efficacy of nickel (a human carcinogen) as an immortalizing agent at nonmutagenic doses raises the alternative possibility that immortalization may occur through an epigenetic mechanism.

Animals↗
PubMed1988

Recognition of Toxoplasma gondii excreted and secreted antigens by human sera from acquired and congenital toxoplasmosis: identification of markers of acute and chronic infection.

While the serological response to somatic antigens of Toxoplasma gondii is currently analysed, little information is available on the antibody response to the antigens excreted and secreted by tachyzoïtes (ESA). This serological study is focused on the immune response towards these antigens which were released by the parasites in cell-free culture medium. Human sera corresponding to 'acute', 'subacute' and 'chronic' acquired infection and sera from infected newborns and from their mothers were analysed by radio-immunoprecipitation with 35S methionine-labelled ESA and with radio-iodinated membrane antigens followed by polyacrylamide gel electrophoresis. In chronic toxoplasmosis, IgG antibodies recognized among ESA major 108, 97, 86, 60, 57, 42, 39 and 28.5 kD antigens; the 108-97 kD doublets and the 28.5 kD antigen seemed characteristic of the chronic phase of toxoplasmosis. In acute infection, IgM antibodies to the 97 kD antigen, the first to appear, seem to contitute good markers of early acute infection. The comparative study of antibody response to membrane antigens showed that, in chronic toxoplasmosis, human sera recognized four antigens of 43, 35, 30 and 22 kD and that, in acute toxoplasmosis, they first recognized the 43 and 30 kD antigens. The serological evolution in congenital toxoplasmosis was the same as in acquired infection. In some cases, the serological profile of the newborn was different from that of his mother, with an additional antibody response to a 170 kD antigen. This study demonstrates in human toxoplasmosis an early, intense and characteristic antibody response against ESA, suggesting that the use of these antigens could lead in the future to improved diagnostic tests.

Acute Disease↗
PubMed1990

Gene technology and the drugs of tomorrow.

The progress of pharmaceutical research depends on three factors: on the evolution of medical needs, on societal attitudes, and on scientific and technical feasibility. Among the factors which are 'internal' to science, molecular biology seems to be the most important driving force, at least for the foreseeable future. The influence of molecular biology on pharmaceutical research is occurring in several distinct phases. The first phase was characterized by the use of gene technology as a production instrument for known proteins. In the second phase, gene technology is instrumental in the identification of novel proteins and in the elucidation of their gene structure and physiological function. A great number of proteins which have therapeutic potential will eventually emerge from this phase, with the more important ones like the hematopoietic factors yet to come. During the third phase, gene technology will provide proteins that can serve as pharmacological tools: receptors, ligands, enzymes, cytokines and other proteins provided by gene technology will enable us to open up new fields of pharmacology from which novel drugs, often low molecular weight chemical entities, will emerge. Finally the fourth phase will be characterized by a knowledge of gene structure and regulation extensive enough to develop a pharmacology of gene regulation and to establish somatic gene therapy. New drugs that can be expected to emerge from the interaction of molecular biology and pharmaceutical research within the next ten to twelve years are discussed. It is expected that pharmaceutical research will in the end be transformed into a discipline in which molecular biology and structural chemistry play dominating roles while synthetic chemistry will be reduced to the role of an important tool.

Genetic Engineering↗