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PubMed1992

Human cytochromes P450: evolution and cDNA-directed expression.

As the first step in the process of carcinogenesis, most chemical carcinogens require metabolic activation by cytochromes P450 for conversion to highly reactive electrophiles that bind covalently to DNA. Studies in rodents suggest that low or high levels of expression of a single P450 can determine susceptibility or resistance to chemically induced cancer. Although rodent systems have been used to explore the molecular basis of chemical carcinogenesis and to identify chemicals capable of damaging genes and causing cancer, it has been understood that marked species differences exist in the expression, regulation, and catalytic activities of different P450s. Thus, large efforts are underway to study the catalytic activities of human P450s directly by expression of their cDNAs in cultured cells. Two systems are being used: a) transient high-level P450 production in HepG2 cells for analysis of catalytic activities, and b) stable expression in human B-lymphoblastoid cells to study promutagen and procarcinogen activation. These studies define the relative contributions of individual P450 forms to the activation of various chemical carcinogens. The B-lymphoblastoid cDNA expression system can also be used to determine whether a chemical will be hazardous or toxic to humans. The most intriguing aspects of P450s are the occurrence of human genetic polymorphisms in P450 expression, which could be a risk factor for chemical carcinogenesis. The best-studied P450 genetic polymorphism is the debrisoquine/sparteine polymorphism which is due to mutant CYP2D6 alleles. Four mutant alleles have been characterized that account for most of the defective CYP2D6 genes in Caucasians. These can be detected by polymerase chain reaction assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Practical evolution and application of direct intracytoplasmic sperm injection for male factor and idiopathic fertilization failure infertilities.

OBJECTIVE: To analyze the introduction of a new assisted fertilization technique for the treatment of severe male factor and idiopathic fertilization failure infertilities. DESIGN: Retrospective analysis of 16-month clinical application of IVF-ET where insemination was performed solely by direct intracytoplasmic sperm injection. SETTING: Clinical IVF-ET program. PATIENTS: Ninety-two couples undergoing 105 cycles of sperm injection. RESULTS: One hundred embryo transfers yielded 28 viable pregnancies (28%) from which eight normal deliveries have occurred to date. Complete cleavage arrest or fertilization failure occurred in four cycles, and one couple had all embryos cryopreserved. One thousand one hundred forty-three eggs were injected of which 173 (15%) degenerated. Four hundred seventy-nine of the surviving 970 eggs became normally fertilized (49%), and 381 of these zygotes (79.5%) developed suitably for cryopreservation or for transfer. Thirty-four of 310 embryos transferred implanted, yielding an implantation rate of 11%. Both testicular and epididymal sperm were used successfully to achieve fertilization and pregnancies, as was sperm retrieved by electroejaculation. Older women and couples suffering from prior idiopathic fertilization failure had a markedly poorer outcome. CONCLUSIONS: These results confirm that the intracytoplasmic sperm injection technique is a successful form of assisted fertilization that can be applied to a wide range of couples at significant risk from fertilization failure.

Adult↗
PubMed2026

Direct link between convergent evolution at sequence level and phenotypic level of septal pore cap in Agaricomycotina.

Several homologous morphological characters, despite sharing apparently similar features, are known to have independently evolved in different lineages multiple times. However, the genetic backgrounds of such morphological convergences remain poorly understood. To detect any correlated amino acid substitutions potentially responsible for morphological convergence at the phenotypic level, we focused on the morphology of the septal pore cap (SPC), a structure involved in mycelia's complex multicellularity in fungi. SPCs are classified into 3 morphological types: perforate, imperforate, and vesiculate. To understand the evolutionary events that occurred at the sequence level during the morphological convergence of perforate SPCs in Agaricomycotina, we examined sequence differences among species with different SPC types by comparative genomic analysis using a single-copy gene dataset from 12 Agaricomycotina genomes with morphological literature of SPC. Our analysis revealed that sequences of 8 genes, including an SPC-related gene spc33, were clustered based on SPC morphology rather than species relationship. Additionally, same amino acid substitutions independently occurred in both lineages in which species with perforate SPCs emerged. These findings suggest that specific amino acid substitutions in spc33 were critical for the emergence of perforate SPCs in multiple lineages. Further, our gene search for spc33 across organisms suggests that spc33 evolved shortly before the emergence of imperforate SPC. This study represents the first step toward elucidating the genetic basis of the morphological evolution of SPC. It contributes to both clarifying the genetic basis underlying morphological convergence and advances the study of fungal evolutionary morphology.

Evolution, Molecular↗
PubMed1985

The evolution and vicissitudes of directional scanning.

The relationship between Directional Scanning and Eye/Hand Dominance is confused. Both seem to have emerged in the Bronze Age, when patterns of artistry and cursive writing became fixed; but, by the time the alphabet was invented, the patterns became complicated by human perversity and racial rivalries, with an interesting, often damaging, legacy to the civilisations and cultures that followed.

Art↗
PubMed1995

The evolution of physician-directed managed care.

The health care industry is evolving. In the near term, POs will become the state of the art in physician-directed managed care. Eventually, POs will merge into fully integrated group practices. From there, regional POs and group practices will develop their own insurance products. But because these organizations will be dominated by physicians who wish to practice medicine, rather than sell insurance, money will be made by appropriately managing risk and providing high-quality care. In time, physicians will take control and "manage" managed care, as they are the only ones--not administrators, executives, or other business people--who are in a position to fundamentally revise the way medicine is practiced.

Capital Financing↗
PubMed1972

Nonmathematical concepts of selection, evolutionary energy, and levels of evolution.

The place of mathematics in hypotheticodeductive processes and in biological research is discussed. (Natural) Selection is defined and described as differential elimination of performed sets at any level. Sets and acting sets are groups of units (themselves sets of smaller units) at any level that may or do interact. A pseudomathematical equation describes directional change (evolution) in sets at any level. Selection is the ram of evolution; it cannot generate, but can only direct, evolutionary energy. The energy of evolution is derived from molecular or chemical levels, is transmitted upwards through the increasingly complex sets of sets that form living systems, and is turned in directions determined by the sum of selective processes, at different levels, which may either supplement or oppose each other. All evolutionary processes conform to the pseudomathematical equation referred to above, use energy as described above, and have a P/OE (ratio of programming to open-endedness) that cannot be measured, but can be related to other P/OE values. Phylogeny and ontogeny are compared as processes af directional change with set selection. Stages in the evolution of multi-cellular individuals are suggested, and are essentially the same as stages in the evolution of some multi-individual insect societies. Thinking is considered as a part of ontogeny involving an irreversible, nonrepetitive process of set selection in the brain.

Biological Evolution↗
PubMed1994

Evolution of homeotic gene regulation and function in flies and butterflies.

It has been proposed that the evolution of homeotic genes parallels, and to some degree directs, the evolution of segment diversity in the myriapod-insect lineage. But the discovery of discrete Antennapedia complex (ANT-C) and bithorax complex (BX-C) gene members in crustacea, chelicerates, annelids and various insects, as well as in vertebrates, indicates that the expansion and diversification of homeotic genes preceded the diversification of arthropods and insects. How, then, have these genes influenced the evolution of body plans? To address this question, we now examine homeotic gene expression and regulation in butterflies (Lepidoptera), which, unlike flies, possess larval abdominal limbs and two pairs of wings. We show that the difference in larval limb number between these insects results from striking changes in BX-C gene regulation in the butterfly abdomen, and we deduce that the wing-patterning genes regulated by Ultrabithorax have diverged in the course of butterfly and fly evolution. These findings have general implications for the role of homeotic genes in animal evolution.

Amino Acid Sequence↗
PubMed1997

Development of the retina is altered in the directly developing frog Eleutherodactylus coqui (Leptodactylidae).

The loss of a free-living larval stage during the evolution of directly developing frogs of the genus Eleutherodactylus resulted in dramatic alterations in ontogeny. Immunostaining for proliferating cell nuclear antigen reveals that in the directly developing frog Eleutherodactylus coqui pervasive cell proliferation occurs throughout the retina even after the plexiform layers have formed. In striking contrast to biphasically developing frogs (e.g. Discoglossus pictus or Xenopus laevis), in E. coqui proliferation becomes restricted to the ciliary margin only after the eye has reached the size typical of a postmetamorphic froglet and after its laminar structure has developed. As a consequence, the retina of E. coqui develops rapidly without recapitulating larva-typical stages. Our results suggest that dissociation of cell proliferation and differentiation can lead to the abbreviation of ontogenies during evolution.

Animals↗
PubMedDate not supplied

[The characteristics of the evolutionary variability of influenza A (H1N1) viruses].

Studies of the antigenic structure of hemagglutinins of influenza A (H1N1) viruses isolated in 1978-1988 using monospecific and monoclonal antibodies demonstrated the strains of the H1N1 subtype to be highly apt to antigenic drift. The evolutional variability of that period was peculiar and characterized by antigenic drift in various directions. In those years, the variants were regularly isolated which had retained the determinants of viruses of 1933-1957 circulation period in their hemagglutinin structure. The variants containing in their hemagglutinin 2 antigenic sites common with A/USSR/090/77 virus and antigenic groupings characterizing the strain specificity of each isolate, were epidemically active. At the same time, epidemically important variants were dominant whose properties were markedly different from those of previously known viruses. Their hemagglutinin contained 2 basically new antigenic determinants. This direction of evolutional development of influenza A (H1N1) virus is the most prospective epidemically.

Animals↗
PubMed1984

Quantitative genetics and developmental constraints on evolution by selection.

It has often been argued that the principles of random mutation and selection are insufficient to account for macroevolutionary phenomena, such as the origin of morphological novelty and directionality in evolution. A third, epigenetic, principle is said to be required and this principle is thought not to be included in microevolutionary theory. The third principle has most recently been identified as internal selection and/or non-random phenotypic effects of mutation. It is shown that the genetic variance/covariance matrix of quantitative genetic theory measures developmental constraints due to internal selection and non-random mutation. The genetic variance/covariance matrix causes the response to selection to deviate from the optimal rate and direction as specified by the selection gradient, which measures direct selection on the phenotypes. Therefore, microevolutionary theory takes account of developmental constraints on evolution by natural selection through the genetic variance/covariance matrix. Theories for predicting the pattern of genetic variance and covariance from stabilizing selection and the phenotypic effects of mutation are discussed.

Biological Evolution↗
PubMed1994

Analysis of directional mutation pressure and nucleotide content in mitochondrial cytochrome b genes.

We present a new approach for analyzing directional mutation pressure and nucleotide content in protein-coding genes. Directional mutation pressure, the heterogenicity in the likelihood of different nucleotide substitutions, is used to explain the increasing or decreasing guanine-cytosine content (GC%) in DNA and is represented by microD, in agreement with Sueoka (1962, Proc Natl Acad Sci USA 48:582-592). The new method uses simulation to facilitate identification of significant A+T or G+C pressure as well as the comparison of directional mutation pressure among genes, even when they are translated by different genetic codes. We use the method to analyze the evolution of directional mutation pressure and nucleotide content of mitochondrial cytochrome b genes. Results from a survey of 110 taxa indicate that the cytochrome b genes of most taxa are subjected to significant directional mutation pressure and that the gene is subject to A+T pressure in most cases. Only in the anseriform bird Cairina moschata is the cytochrome b gene subject to significant G+C pressure. The GC% at nonsynonymous codon sites decreases proportionately with increasing A+T pressure, and with a slope less than one, indicating a presence of selective constraints. The cytochrome b genes of insects, nematodes, and eumycotes are subject to extreme A+T pressures (microD = 0.123, 0.224, and 0.130) and, in parallel, the GC% of the nonsynonymous codon sites has decreased from about 0.44 in organisms that are not subjected to A+T or G+C pressure to about 0.332, 0.323, and 0.367, respectively. The distribution of taxa according to the GC% at nonsynonymous codon sites and directional mutation pressure supports the notion that variation in these parameters is a phylogenetic component.

Biological Evolution↗
PubMedDate not supplied

[New concepts in the approach to congenital strabismus].

The first part of the paper reviews the clinical symptoms of congenital strabismus. Congenital strabismus passes four stages during its evolution. Spontaneous evolution becomes either alternant strabismus (stage IV a) or monolateral strabismus (stage IV b). The early treatment is to direct the evolution to the "a" form of stages III and IV and mainly consists of optical correction and occlusion.

Fixation, Ocular↗
PubMed1998

Facial nerve surgery in the 19th and early 20th centuries: The evolution from crossover anastomosis to direct nerve repair.

The historical aspects of facial nerve (FN) anatomy and of Bell's palsy have long been favorite topics of otologic historians. Little attention has been paid, however, to the evolution of FN surgery, a subject with a remarkably rich and engaging history. In the early 13th century, Roland, an Italian surgeon, used a red hot iron to coapt severed nerve endings. In the 17th century, Ferrara, another Italian, sutured injured nerves with tortoise tendon dipped in hot red wine. It was not until the late 19th century that peripheral nerve suture became a subject of serious scientific study. Although it is ironic, the course of events suggests that the evolution of FN repair was greatly stimulated by the development of the modern mastoid operation. Whereas the simple mastoid operation practiced by Wilde (1853) and others carried little risk of FN injury, more adventuresome procedures such as radical mastoidectomy (Kessel, 1885) carried a much greater risk. The abundance of iatrogenic palsies during this era undoubtedly did much to motivate surgeons to seek a better means of restoring facial animation. Most surgeons would be surprised to learn that crossover anastomoses predated direct nerve repair by nearly half a century. In 1879, the German surgeon Drobnik performed the first facial-spinal accessory anastomosis. Over the next two decades, numerous articles were written (most notably by Sir Charles Balance and Harvey Cushing) on crossovers between the FN and cranial nerves IX, X, XI, and XII. Although a few tentative attempts at reapproximating severed FNs took place in the first two decades of this century, it was not until 1925 that an actual suture repair of an intratemporal injury was undertaken. This feat was first accomplished by the famous hand surgeon Sterling Bunnell and shortly thereafter by the otolaryngologist Robert Martin. The evolution of FN surgery in the days predating the operating microscope is a rich tapestry of colorful personalities and clashing egos, which saw promising advances relegated to obscurity and some previously obscure techniques become progressively more promising.

Anastomosis, Surgical↗
PubMed1992

Cranial ontogeny in the direct-developing frog, Eleutherodactylus coqui (Anura: Leptodactylidae), analyzed using whole-mount immunohistochemistry.

Direct development in amphibians is an evolutionarily derived life-history mode that involves the loss of the free-living, aquatic larval stage. We examined embryos of the direct-developing anuran Eleutherodactylus coqui (Leptodactylidae) to evaluate how the biphasic pattern of cranial ontogeny of metamorphosing species has been modified in the evolution of direct development in this lineage. We employed whole-mount immunohistochemistry using a monoclonal antibody against the extracellular matrix component Type II collagen, which allows visualization of the morphology of cartilages earlier and more effectively than traditional histological procedures; these latter procedures were also used where appropriate. This represents the first time that initial chondrogenic stages of cranial development of any vertebrate have been depicted in whole-mounts. Many cranial cartilages typical of larval anurans, e.g., suprarostrals, cornua trabeculae, never form in Eleutherodactylus coqui. Consequently, many regions of the skull assume an adult, or postmetamorphic, morphology from the inception of their development. Other components, e.g., the lower jaw, jaw suspensorium, and the hyobranchial skeleton, initially assume a mid-metamorphic configuration, which is subsequently remodeled before hatching. Thirteen of the adult complement of 17 bones form in the embryo, beginning with two bones of the jaw and jaw suspensorium, the angulosplenial and squamosal. Precocious ossification of these and other jaw elements is an evolutionarily derived feature not found in metamorphosing anurans, but shared with some direct-developing caecilians. Thus, in Eleutherodactylus cranial development involves both recapitulation and repatterning of the ancestral metamorphic ontogeny.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

[Genetic differentiation of Caucasian wood mice: comparison of isozymic, chromosomal and molecular divergence].

Data on the complex genetic analysis of three sympatric species of Caucasian wood mice, Apodemus ponticus, A. fulvipectus, and A. uralensis are presented. A high degree of genetic differentiation at the isozymic, karyological and molecular (nuclear DNA) levels was revealed. The genetic distances between each pair of species varied significantly within a wide range depending on the analyzed level of the organization of genetic material. Mean values of genetic divergence from one species to another were also variable. These findings indicated that evolution of chromosomes was slower than that of isozymes, and the degree of species divergence was similar on cytogenetic and molecular levels. They also suggested that the rates of species evolution could vary in different phyletic lineages and on different levels of organization. Some phyletic lineages of Apodemus could be distinguished by different directions of evolution.

Animals↗