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Biomedical subjects

S L Martin

Publications and source records attributed to S L Martin.

At least 109 records · Page 6Linked to original sources
PubMed1989

Genetic and biochemical characterization of the thymidine kinase gene from herpesvirus of turkeys.

The thymidine kinase gene encoded by herpesvirus of turkeys has been identified and characterized. A viral mutant (ATR0) resistant to 1-beta-D-arabinofuranosylthymine was isolated. This mutant was also resistant to 1-(2-fluoro-2-deoxy-beta-D-arabinofuronosyl)-5-methyluracil and was unable to incorporate [125I]deoxycytidine into DNA. The mutant phenotype was rescued by a cloned region of the turkey herpesvirus genome whose DNA sequence was found to contain an open reading frame similar to that for known thymidine kinases from other viruses. When expressed in Escherichia coli, this open reading frame complemented a thymidine kinase-deficient strain and resulted in thymidine kinase activity in extracts assayed in vitro.

Amino Acid Sequence↗
PubMed1989

Mechanisms that lead to disease of the endocrine system in animals.

Endocrine glands are collections of specialized cells that synthesize, store, and release their secretions directly into the blood stream. They are sensing and signalling devices located in the extracellular fluid compartment and are capable of responding to changes in the internal and external environments to coordinate a multiplicity of activities that maintain homeostasis. Diseases of the endocrine system are encountered in many animal species and present challenging diagnostic problems. The major pathogenic mechanisms responsible for disturbances in endocrine function include: 1) primary hyperfunction of an endocrine gland; 2) secondary hyperfunction; 3) primary hypofunction of an endocrine gland; 4) secondary hypofunction; 5) endocrine hyperactivity secondary to diseases of other organs; 6) hypersecretion by nonendocrine tumors of hormone-like substances; 7) failure of fetal endocrine function; 8) endocrine dysfunction due to failure of target cell response; 9) endocrine dysfunction resulting from abnormal degradation of hormone; and 10) iatrogenic syndromes of hormone-excess. For each major category, several specific disease problems have been selected to illustrate the morphologic and functional changes that characterize the response of a particular endocrine gland to disruption of function.

Animals↗
PubMed1989

The effects of xenobiotics on the structure and function of thyroid follicular and C-cells.

The mammalian thyroid gland is composed of 2 distinct endocrine cell populations concerned with the synthesis of 2 different classes of hormones. Follicular cells secrete the metabolically active iodothyronines whereas the C-(parafollicular) cells are concerned with the production of calcitonin, a hormone that influences blood levels of calcium and phosphorus, and bone cell metabolism. The synthesis of metabolic thyroid hormones is different than in other endocrine glands because the final assembly of hormone occurs within the follicular lumen. This extracellular synthesis of thyroid hormones is made possible by thyroglobulin, a glycoprotein synthesized by follicular cells. The secretion of thyroid hormones under the influence of pituitary thyrotrophin (TSH) from stores in the luminal colloid is initiated by elongation of microvilli and formation of pseudopods. FD&C Red No. 3 is a tetraiodinated derivative of fluorescein which in lifetime studies increases the incidence of thyroid follicular cell adenomas in male Sprague-Dawley rats. The striking changes in circulating levels of thyroid hormones and morphologic evidence of follicular cell stimulation are the result of alterations in the peripheral metabolism of thyroxine. An inhibition by FD&C Red No. 3 of 5'-deiodinase in the liver and kidney would explain the lower serum triiodothyronine (T3) levels. The pituitary, sensing the lowered circulating levels of T3, increased the secretion of thyroid stimulating hormone which resulted in the morphologic evidence of follicular cell stimulation in the long-term studies. Other xenobiotics increase the incidence of thyroid tumors in rodents by a direct effect on the thyroid gland to disrupt 1 of 3 or more possible steps in the biosynthesis of thyroid hormones. Physiologic perturbations alone, such as iodine deficiency or partial thyroidectomy, can disrupt thyroid hormone economy in rodents and, if sustained, increase the development of thyroid tumors. The wide variety of drugs, chemicals, and physiologic perturbations which increase thyroid tumor development appear to act through a secondary (indirect) mechanism to promote tumor development by causing a long-standing hypersecretion of thyroid stimulating hormone. Nodular and/or diffuse hyperplasia of C-cells occurs with advancing age in many strains of laboratory rats and in response to long-term hypercalcemia in certain animal species and human beings. Focal or diffuse hyperplasia often precedes the development of C-cell neoplasms. Radiation and the feeding of diets high in vitamin D resulting in hypercalcemia have been reported to increase the incidence of C-cell tumors in rats.

Animals↗
PubMed1986

Conservation throughout mammalia and extensive protein-encoding capacity of the highly repeated DNA long interspersed sequence one.

We report an investigation of the structure, evolutionary history, and function of the highly repeated DNA family named Long Interspersed Sequence One (L1). Hybridization studies show, first, that L1 is present throughout marsupial and placental mammalian orders. Second, L1 is more homologous within these species than between them, which suggests that it has undergone concerted evolution within each mammalian lineage. Third, on the whole L1 diverges in accordance with the fossil record. This suggests that it arose in each lineage rather by inheritance from a common ancestral family, which was present in the progenitor to mammals, than by cross-species transmission. Alignment of 1.6 X 10(3) bases of primate and mouse L1 DNA sequences shows a predominance of silent mutations within aligned long open reading frames, indicating that at least this part of L1 has produced functional protein. The observation of additional long open reading frames in further unaligned DNA sequences suggests that a minimum of 3.2 X 10(3) bases or at least half of the L1 structure is a protein-coding sequence. Thus L1, which contains about 100,000 members in mouse, is by far the most repetitive family of which a subset comprises functional protein-encoding genes. The ability of the putative protein-encoding regions of mouse L1 to hybridize to L1 homologs throughout the Mammalia implies that these sequences have been subject to conservative selection upon protein function in all mammalian lineages, rather than in a few. L1 is therefore a highly repeated family of genes with both a widespread and an ancient history of function in mammals.

Amino Acid Sequence↗
PubMed1986

An analysis of replacement and synonymous changes in the rodent L1 repeat family.

L1 is a family of long interspersed repetitive sequences in mammals that includes the BamHI family in rodents and the KpnI family in primates. Previous studies have shown that L1 repeats contain a long open reading frame and that the family evolves in concert. Working with 32 rodent elements for which DNA sequence is available, we used the distribution of replacement and synonymous changes to determine which L1 lineages had been expressing their reading frame. The evidence obtained is consistent with there having been a small number of L1 genes that have been expressing a functional protein. Much of the concerted evolution in L1 is accounted for by the tendency of these functioning L1 genes to continually create nonfunctional pseudogenes by reinsertion into the genome of sequences derived from their transcripts. The gain of new pseudogenes is balanced by the loss of old pseudogenes with a half-life of 2 Myr. Therefore, most of the observed L1 repeats are at a dead end with respect to either the expression of the L1 protein or the potential to elaborate further copies of themselves. However, the turnover of L1 pseudogenes is sufficient to constitute a vast flux of sequences into and then out of the flanking regions of all cellular genes. If the presence of flanking L1 pseudogenes affects the expression of other genes in even a subtle fashion, this process should represent a major source of genetic variation. A second level of concerted evolution occurs within the functional L1 sequences in a pattern that did not meet our expectations for selfish DNA. Also, in spite of the marked suppression of replacement relative to synonymous changes in functioning L1 genes, they evolve at an overall rate accelerated to the level of their own pseudogenes.

Animals↗
PubMed1985

Tempo and mode of concerted evolution in the L1 repeat family of mice.

A 300-bp DNA sequence has been determined for 30 (10 from each of three species of mice) random isolates of a subset of the long interspersed repeat family L1. From these data we conclude that members of the L1 family are evolving in concert at the DNA sequence level in Mus domesticus, Mus caroli, and Mus platythrix. The mechanism responsible for this phenomenon may be either duplicative transposition, gene conversion, or a combination of the two. The amount of intraspecies divergence averages 4.4%, although between species base substitutions accumulate at the rate of approximately 0.85%/Myr to a maximum divergence of 9.1% between M. platythrix and both M. domesticus and M. caroli. Parsimony analysis reveals that the M. platythrix L1 family has evolved into a distinct clade in the 10-12 Myr since M. platythrix last shared a common ancestor with M. domesticus and M. caroli. The parsimony tree also provides a means to derive the average half-life of L1 sequences in the genome. The rates of gain and loss of individual copies of L1 were estimated to be approximately equal, such that approximately one-half of them turn over every 3.3 Myr.

Animals↗
PubMed1984

Dispersal process associated with the L1 family of interspersed repetitive DNA sequences.

We have determined the complete nucleotide sequence for five members of the L1Md repetitive family from the beta-globin gene region of the BALB/c mouse. The five repeats are different lengths, each terminating at the 5' end at different points with respect to one another. We have analyzed the nucleotides around the endpoints of the five repeats for clues as to the mechanisms involved with the dispersal and 5' truncation of this repeat family. Each L1 member is flanked by a pair of short direct repeats. Since these direct repeats differ in length and sequence in each of the five cases, the dispersal mechanism does not involve a sequence targeted process. The sequence at the 3' end is conserved and its organization resembles the 3' end of a polyadenylated RNA, suggesting that transcripts of the repeat are involved in the dispersal process either directly or as intermediates in the generation of complementary DNA copies of the sequence. One of the L1 repeats is a recent insertion, since it is found in the Hbbd chromosome, but not in the Hbbs chromosome. This suggests a dispersal process that has been active as recently as 4 million years ago.

Animals↗
PubMed1984

A large interspersed repeat found in mouse DNA contains a long open reading frame that evolves as if it encodes a protein.

DNA sequence analysis of a region contained within a large, interspersed repetitive family of mice reveals a long open reading frame. This sequence extends 978 base pairs between two stop codons, creating a reading frame that is open for 326 amino acids. The DNA sequence in this region is conserved between three distantly related Mus species, as well as between mouse and monkey, in a manner that is characteristic of regions undergoing selection for protein function.

Amino Acid Sequence↗
PubMed1983

Rise and fall of the delta globin gene.

This paper examines the molecular basis for the origin and subsequent silencing of the delta globin gene during the evolution of higher primates. We cloned and sequenced the delta gene from representatives of the two most distantly related types of Old World monkeys in which the gene is silent. The silent delta genes of these two monkeys (rhesus and colobus) are highly homologous to each other (97.5%) and to the functional human delta gene (94%). The presumed mutation that silenced the delta gene is therefore unlikely to be obscured by later mutations at the same site. This silencing mutation could have affected transcription since we find no delta transcript in rhesus bone marrow. Furthermore, the delta globin genes from colobus and rhesus monkeys are many times less efficient than the human delta gene in a cell-free transcription assay. The two Old World monkeys share only three nucleotide substitutions in the first 100 base-pairs of the DNA sequence 5' to the site for initiation of transcription when compared to human delta. It is likely that the in vitro silencing of the delta gene was brought about by one (or a combination) of these three substitutions. Three analysis shows how the delta sequences are related to those for other beta-like genes, including the colobus beta gene whose sequence we report. One part of the delta gene appears to be derived from a (pseudo?) beta gene that diverged from beta before the divergence of mice and men. The other part is closely related to the beta gene of higher primates. The mosaic nature of the delta gene is apparently due to a partial conversion which took place between the pseudo beta and the functional beta gene before the divergence of the lineages leading to Old World monkeys and hominoids.

Animals↗
PubMed1983

Concordance among self-regulated responses: is self-regulatory ability a psychophysiological "trait"?

The purposes of this study were to examine whether or not self-regulation of physiological responses demonstrates day-to-day reliability, to determine the degree of individual subject consistency (or concordance) in the ability to self-regulate across several different physiological responses, and, finally, to explore the impact of biofeedback training on interresponse concordance. Twenty normal subjects participated in six bidirectional self-regulation sessions-the first and last sessions involving instructions only, and the remainder, biofeedback. Self-regulation scores consisted of the absolute difference between increase and decrease trial means. The average test-retest reliability coefficients (rs) for the self-regulation scores, across the four biofeedback sessions, were a highly significant .50, .68, .30, and .47 for EEG, EMG, HR, and SCL, respectively. By contrast, the average concordance among the self-regulation scores for the four feedback sessions, estimated by Kendall's coefficient of concordance, was a marginally significant 39% of the possible variance of the rank sums. This corresponds to an average between-response rs value only of .19. The concordance level from the initial no-feedback (i.e., instructions only) session was not significant. Multivariate concordance levels did increase during the first three feedback sessions, but declined at the fourth, and again was nonsignificant during the final no-feedback session. Among the individual self-regulation response pairings, only the EEG/EMG combination was consistently associated during the no-feedback sessions. The present results suggest that self-regulatory ability is neither a highly unitary "trait"-like phenomenon nor an entirely response-specific event, but may vary considerably as a function of subject factors, or the situational circumstances, under which it is measured.

Biofeedback, Psychology↗
PubMed1982

Autoimmune lymphocytic thyroiditis in dogs.

Primary diseases of the thyroid gland, especially lymphocytic thyroiditis and idiopathic follicular atrophy, were the most common lesions associated with clinical hypothyroidism in pet dogs. Lymphocytic thyroiditis resembled naturally occurring lymphocytic thyroiditis in the Obese-strain of White Leghorn chickens and Hashimoto's thyroiditis in man. The morphology of the thyroid lesion and frequent occurrence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated in pet dogs. Thyroid lesions similar to naturally occurring autoimmune thyroiditis in experimental dogs were induced by a local thyroidal graft-versus-host reaction. The lesions observed in the thyroid lobe which was not injected with immunocompetent cells appeared to develop from the formation of thyroid antibodies in the gland by migrating host lymphocytes. Autoimmune lymphocytic thyroiditis occurred secondary to an unrelated immune response occurring in target tissue.

Animals↗
PubMed1981

The untranslated regions of beta-globin mRNA evolve at a functional rate in higher primates.

We have sequenced the 3' and 5' untranslated regions of beta-globin mRNAs from cebus monkey, rhesus monkey and chimpanzee. A comparison with the corresponding human sequences reveals that the rate of sequence divergence among the higher primates is the same in the 3' and 5' noncoding regions and that this rate is several times lower than the rate for silent substitutions in the coding regions. In addition, the rate of sequence divergence in the 3' untranslated region of the primate beta-globin nRNA is several times lower than the rate calculated for this region from other comparisons. The low rate of sequence divergence in the noncoding 3' end of the primate beta-globin mRNAs may indicate a specialized and significant function for this region in the higher primates.

Animals↗
PubMed1981

Histologic and ultrastructural evaluation of thyroid lesions associated with hypothyroidism in dogs.

Thyroid lesions in 16 pet dogs with hypothyroidism were evaluated by light and electron microscopy. Lymphocytic thyroiditis, found in seven dogs, was characterized by diffuse infiltration of the thyroid gland by lymphocytes, plasma cells and macrophages with formation of some lymphoid nodules and destruction of follicles, progressing to replacement of most of the thyroid by fibrous connective tissue. The basement membrane around follicles was thick and had electron-dense deposits. The morphology of the thyroid lesions and the presence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated. Idiopathic follicular atrophy, found in nine dogs, was characterized by loss of thyroid parenchyma and replacement by adipose connective tissue. Degeneration of individual follicular cells was present in the early stage, with exfoliation into the colloid and interfollicular area. Most of the thyroid gland consisted of adipose connective tissue with either interspersed small follicles or individual follicular cells that had dilated rough endoplasmic reticulum, large Golgi apparatus, and intracytoplasmic microfollicles in the advanced stage. Follicular atrophy was a degenerative lesion of follicular cells of unknown cause, not associated with inflammatory destruction in the thyroid gland.

Animals↗
PubMed1981

Induced lymphocytic thyroiditis in dogs: effect of intrathyroidal injection of thyroid autoantibodies.

Multifocal infiltrations of lymphocytes and macrophages were present in the thyroid glands of dogs 1 month after an intrathyroidal injection (0.5 ml) of canine serum containing thyroglobulin autoantibodies. The development of thyroiditis was associated with a gradual increase in the incorporation of tritiated thymidine by the peripheral blood mononuclear cells. There was no alteration in circulating thyroid hormone values or thyroglobulin autoantibody titer for 1 month. Control dogs given a similar volume of canine serum without thyroglobulin antibodies did not have an inflammatory reaction in the thyroid gland, and the phytomitogen responses of lymphocytes did not change, compared with base-line values. An intrathyroidal injection of canine thyroglobulin autoantibodies induced lesions similar to naturally occurring lymphocytic thyroiditis in dogs, indicating that thyroid autoantibodies have an important role in the pathogenesis of immune-mediated thyroiditis.

Animals↗
PubMed1981

Lymphocytic thyroiditis in dogs; induction with a local graft-versus-host reaction.

Fifty million allogeneic canine lymphocytes were injected in the left lobe of the thyroid gland of 10 dogs. The left lobe of the gland was surgically removed at 1 and 4 weeks after injection. The intrathyroidal injection of immunocompetent cells resulted in local graft vs host reaction within the thyroid gland. Multifocal infiltration of lymphocytes, plasma cells, and macrophages associated with scattered, isolated, or small groups of degenerated follicular cells were present in the follicular wall and colloid on day 7. Thyroidal lesions at 1 month after injection were characterized by extensive destruction of follicular cells, disseminated foci of mononuclear cell infiltration, and electrondense deposits between follicular cells and the basement membrane. The contralateral (noninjected) lobe of the thyroid gland at 4 weeks after injection was infiltrated by lymphocytes, macrophages, and many plasma cells. The inflammatory lesions were associated with multifocal areas of degeneration of follicular cells and focal electron-dense thickenings of the basement membrane. The noninjected lobe, following hemithyroidectomy at 1 week after injection of the thyroid gland undergoing graft-vs-host reaction, either had a focal infiltration of polymorphonuclear leukocytes, lymphocytes, macrophages, and mast cells or had no significant lesions.

Animals↗