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Biomedical subjects

C M Watson

Publications and source records attributed to C M Watson.

At least 19 recordsLinked to original sources
PubMed2002

cDNA cloning of the polymeric immunoglobulin receptor of the marsupial Macropus eugenii (tammar wallaby).

cDNA encoding a marsupial polymeric immunoglobulin receptor (pIgR) was isolated from Macropus eugenii (tammar wallaby) mammary lymph node primarily by reverse transcriptase coupled polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) PCR. This resulted in a 5' truncated clone and, in order to obtain the full-length sequence, genomic walking PCR was utilized. The complete sequence consists of 2696 bp of cDNA and encodes a predicted polypeptide of 732 amino acids. The wallaby sequence is highly conserved in relation to the only other reported marsupial pIgR sequence, that of Trichosurus vulpecula (brushtail possum), having a nucleotide identity of 86.7% and a deduced amino acid identity of 79.9%. The wallaby nucleotide sequence also has a moderate degree of similarity with the pIgR sequences of eutherian mammals, being most similar to that of the rat, with an identity of 63.1%. At the amino acid level, in comparison to eutherian sequences, the wallaby pIgR is most similar to that of humans with an identity of 52.6%. pIgR phylogenetic trees were constructed for tammar wallaby, brushtail possum and several eutherian mammal cDNA and deduced amino acid sequences. In both DNA and protein analyses, the eutherian sequences formed a sister clade to the exclusion of the marsupial sequences, in agreement with the current view of mammalian evolution.

Amino Acid Sequence↗
PubMed2002

Sex chromosome elimination, X chromosome inactivation and reactivation in the southern brown bandicoot Isoodon obesulus (Marsupialia: Peramelidae).

Cytogenetic studies have shown that bandicoots (family Peramelidae) eliminate one X chromosome in females and the Y chromosome in males from some somatic tissues at different stages during development. The discovery of a polymorphism for X-linked phosphoglycerate kinase (PGK-1) in a population of Isoodon obesulus from Mount Gambier, South Australia, has allowed us to answer a number of long standing questions relating to the parental source of the eliminated X chromosome, X chromosome inactivation and reactivation in somatic and germ cells of female bandicoots. We have found no evidence of paternal PGK-1 allele expression in a wide range of somatic tissues and cell types from known female heterozygotes. We conclude that paternal X chromosome inactivation occurs in bandicoots as in other marsupial groups and that it is the paternally derived X chromosome that is eliminated from some cell types of females. The absence of PGK-1 paternal activity in somatic cells allowed us to examine the state of X chromosome activity in germ cells. Electrophoresis of germ cells from different aged pouch young heterozygotes showed only maternal allele expression in oogonia whereas an additional paternally derived band was observed in pre-dictyate oocytes. We conclude that reactivation of the inactive X chromosome occurs around the onset of meiosis in female bandicoots. As in other mammals, late replication is a common feature of the Y chromosome in male and the inactive X chromosome in female bandicoots. The basis of sex chromosome loss is still not known; however later timing of DNA synthesis is involved. Our finding that the paternally derived X chromosome is eliminated in females suggests that late DNA replication may provide the imprint for paternal X inactivation and the elimination of sex chromosomes in bandicoots.

Animals↗
PubMed2001

Gender differences in adolescent self-esteem: an exploration of domains.

The relationship between gender and global self-esteem in adolescence, while modest, has been well established, with boys consistently scoring higher than girls. In the present study, we sought to understand gender differences in adolescent self-esteem in terms of its component parts. With a relatively large (n = 545) sample of adolescents, drawn from Grades 8, 10, and 12, we specified 8 domains of adolescent self-esteem (personal security, home/parents, peer popularity, academic competence, attractiveness, personal mastery, psychological permeability, and athletic competence) across a number of different instruments and brought them together into a common assessment superstructure. Gender differences as well as the relative contributions of the different domains to overall self-esteem scores were measured. As predicted, boys attained slightly higher global self-esteem scores than girls did, by a difference of .22 standard deviation units. Contrary to our expectation of more balanced domain effects, boys significantly outperformed girls in 6 of 8 domains, whereas the 2 remaining domains exhibited no significant gender differences. There were no main or interaction effects for grade level. In terms of relative contribution of these domains to global self-esteem for the 2 genders, global self-esteem in boys and girls is predicted in very similar strengths and in the same order of magnitude by identical domains of self-esteem: home/parents, personal security, academic competence, attractiveness, and personal mastery--yielding multiple R2s from .88 to .91.

Adolescent↗
PubMed2001

Cell lineage determination in the mouse.

During the peri-implantation development of the mouse embryo from the blastocyst through gastrulation, Pou5f1 (OCT-4) down-regulation is closely linked to the initial step of lineage allocation to extraembryonic and embryonic somatic tissues. Subsequently, differentiation of the lineage precursors is subject to inductive tissue interactions and intercellular signalling that regulate cell proliferation and the acquisition of lineage-specific morphological and molecular characteristics. A notable variation of this process of lineage specification is the persistence of Pou5f1 activity throughout the differentiation of the primordial germ cells, which may underpin their ability to produce pluripotent progeny either as stem cells (embryonic germ cells) in vitro or as gametes in vivo. Nevertheless, intercellular signalling still plays a critical role in the specification of the primordial germ cells. The findings that primordial germ cells can be induced from any epiblast cells and that they share common progenitors with other somatic cells provide compelling evidence for the absence of a pre-determined germ line in the mouse embryo.

Animals↗
PubMed2001

Academic, motivational, and emotional correlates of adolescent dating.

This study is an examination of the relationship between dating status and academic achievement, academic motivation, depression, and self-esteem; it is an investigation of the differential effects wielded by gender and age (grade level) of the dating adolescent in each of these domains. Participants were a relatively large gender-balanced adolescent group (N = 380) from Grades 8, 10, and 12. Dating status was studied first as a binary variable (frequent versus infrequent dating) and second as a dating spectrum, including steady, frequent, and infrequent dating. Results showed that adolescents who dated frequently (more than once or twice a month), whether they were boys or girls, relatively young (8th grade) or more mature (l0th and 12th grades), exhibited consistently and significantly lower levels of academic achievement and academic motivation and higher levels of depressive symptoms. There were no significant effects of dating status on global self-esteem, but, as hypothesized, subscale analyses revealed important subscale-differentiated effects.

Adolescent↗
PubMed2000

Sexual development in marsupials: genetic characterization of bandicoot siblings with scrotal and testicular maldevelopment.

In marsupials testis determination requires the presence of a Y chromosome. The sex determining region on the Y gene (SRY) is necessary for testicular development in eutherians and it is assumed to play a similar role in marsupials. Relatively few studies have investigated the genetic basis of sexual development, and as yet there is no direct evidence that SRY is required for testis development in marsupials. Studies on intersexual marsupials have revealed a fundamental difference between marsupial and eutherian sex determination. The scrotum of marsupials is analogous, not homologous, to the eutherian scrotum and is under the control of X-linked genes not androgens. The current study describes two bandicoot (Isoodon macrourus) siblings. Both siblings had underdeveloped male reproductive tracts and testicular dysgenesis, one was ascrotal and the other had a diminutive scrotum. Their karyotypes were normal for this species which eliminates the Y chromosome from some somatic tissues. SRY was detected by Southern blotting. SRY, ubiquitin activating enzyme-1 on the Y (UBE1Y) and glucose 6-phosphate dehydrogenase (G6PD) gene expression were examined. UBE1Y was widely expressed in many tissues. SRY gene expression was much lower than normal in the abnormal siblings and may be responsible for their failure of testicular and epididymal development. The cause of their scrotal abnormalities is unknown. It is possible that the separate defects of scrotal and testis development in the two siblings, which had normal relatives, were due to a mutation in a gene common to both developmental pathways.

Animals↗
PubMed1998

Sex-chromosome elimination in the bandicoot Isoodon macrourus using Y-linked markers.

Cytogenetic studies have shown that the Y chromosome is eliminated from many somatic cell types of the bandicoot Isoodon macrourus, an Australian marsupial. Molecular techniques allow examination of a greater range of tissue types than that possible using cytogenetic techniques. The presence or absence of the Y chromosome was established using partial sequences of the Y-linked SRY and UBE1Y genes in I. macrourus, with the X-linked gene G6PD as a control. We show that a very small proportion of cells comprising hematopoietic tissues, and even fewer cells in peripheral blood, retain the Y chromosome. The Y chromosome is retained in most brain, liver, kidney, and lung cells and in cardiac and skeletal muscle. We also show that the bandicoot Y chromosome is retained in some cell types within tissues previously believed to completely eliminate the Y chromosome.

Amino Acid Sequence↗
PubMed1997

SRY and karyotypic status of one abnormal and two intersexual marsupials.

An intersexual agile wallaby (Macropus agilis) with a penis, a pouch and four teats had a sex-chromosome constitution of XXY in lymphocytes and cultured fibroblasts; the sex-determining region Y (SRY) gene was present, consistent with the presence of a testis. An intersexual eastern grey kangaroo (Macropus giganteus) with a small empty scrotum and no penis, and an abnormal red kangaroo (Macropus rufus) with no penis, pouch or teats, both had XX sex-chromosome complements; the SRY gene was not present, consistent with testis absence. The agile wallaby and grey kangaroo described here provide further evidence that scrotal development in marsupials is independent of the Y chromosome. The cause of the abnormalities in the XX individuals cannot be determined until candidate genes are identified. These animals provide a basis for further genetic studies into marsupial intersexuality and sex differentiation.

Animals↗
PubMed1996

Intersexual phenotypes and sex chromosome complements of five South American opossums (Monodelphis domestica).

Intersexual opossums (Monodelphis domestica) from a large captive colony are described. These are the first naturally existing New World (didelphoid) intersexual marsupials for which reproductive phenotype and sex chromosome constitution are reported. One animal was XX, two were XY, and two were XO; all had lower body weight than normal males or females and the overall appearance of females. They were first recognized as abnormal by the presence of a small flaccid, nonstalked scrotum, markedly smaller than the scrotum of a normal male but in an equivalent position cranial to the cloacal aperture. Each scrotum contained a core of fatty connective tissue, but none contained testicular tissue. Teat patterns, seen only after close shaving of the hair over the area of the teat field, varied within and between the various sex genotypes, with one XY and one XO having the paired rudiments typical of normal males. All individuals had gonads, with no transabdominal migration. In the XX intersex there were mature ovaries with Graffian follicles, but in the XY and XO intersexes there was gonadal dysgenesis. The urogenital tract of all was female in appearance but was immature except in the XX intersex. Development of the scrotum and of the teat primordia can be explained on the basis of regulatory gene influences on the X chromosome. Intersex incidence in the colony is probably much higher than that observed because of ascertainment bias.

Animals↗
PubMed1991

Suppression of demyelination by mitoxantrone.

The mode of action of the immunosuppressant mitoxantrone was examined in murine models of demyelinating disease. The drug has been shown to block antigen induced proliferative activity and to inhibit myelin degradation by leucocytes from paralysed mice. Mitoxantrone blocked myelin breakdown by macrophages although phagocytosis was not affected. Further evidence was obtained to indicate that mitoxantrone acts therapeutically in reducing, or at high dose, preventing signs of EAE developing in mice immunized with spinal cord homogenate and Freund's complete adjuvant. Mitoxantrone also significantly inhibited the incidence of relapse when treatment was initiated during the post-acute remission period.

Animals↗
PubMed1990

Degradation of human myelin in vitro by leucocytes from patients with multiple sclerosis.

In order to study the possible autoimmune basis of multiple sclerosis (MS) a quantitative method has been used to investigate breakdown of human myelin in vitro. We found that serum from MS patients and controls was generally devoid of any myelin degradative activity. However, isolated peripheral blood mononuclear cells from 43% of MS patients showed significant myelin degradative activity as did those from 61.5% of patients with rheumatoid arthritis (RA). Myelin degradation by cells was found in only 13% of patients with other neurological diseases and in no healthy controls. It is proposed that this non-specific peripheral cellular immune degradative activity originates from cells activated within the central nervous system of MS patients or the joints of individuals with RA. As a result, activity in the blood only indirectly reflects the ongoing inflammatory response at the primary site, accounting for the lack of correlation between changes in the blood and the clinical status of the MS patient. We further propose that the lack of in vitro myelin degradative activity in cells recovered from the cerebrospinal fluid is due to autoaggressive cells being sequestered to the brain.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1988

Nervous and immune system disorders in multiple sclerosis.

Multiple sclerosis is probably an acquired infectious disease with an autoimmune response relating to damage to the white matter of the central nervous system. There is evidence of continued intrathecal synthesis of oligoclonal antibody and there are perivascular inflammatory cell infiltrates close to areas of demyelination in the central nervous system. Following adoptive transfer, cells sensitized to the myelin basic protein can cause demyelinating disease in rodent recipients. Unlike the peripherally-mediated immune changes in the experimental model it is argued that autoaggressive cells are generated within the CNS in multiple sclerosis. The possible mechanism of cellular demyelination is discussed and the implication for therapy is reviewed.

Animals↗
PubMed1988

An in vitro micromethod for the quantitative assessment of central demyelination.

We report the development of a simple and reliable method for the study of demyelination in vitro based on the measurement of 2':3'-cyclic nucleotide 3'-phosphodiesterase in isolated myelin. Using only small quantities of myelin (equivalent to 100 micrograms of myelin protein) the system was tested under conditions that are believed to approximate those found at the site of an inflammatory demyelinating lesion. Treatment with a combination of trypsin, phospholipase A2, and lysophosphatidylcholine was used to evaluate the method. This microsystem has the potential not only for testing the myelinotoxicity of soluble factors but also for investigating the involvement of inflammatory cells in the demyelinating process. Myelin degradation by elicited peritoneal macrophages could be demonstrated at relatively high densities of these cells. Nylon wool purified lymph node T cells from myelin basic protein-primed SJL/J mice, after selective expansion with antigen and interleukin 2, failed to induce any significant myelin breakdown unless a limited number of syngeneic activated macrophages were also present. T cells from mice that had been inoculated with keyhole limpet haemocyanin failed to show any effect. The advantages of this technique over other in vitro systems are that it enables the study of demyelination using syngeneic sources of myelin and defined cell populations.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1984

Shortening of bleeding time by 1-deamino-8-D-arginine vasopressin in various bleeding disorders.

To evaluate the effect of 1-deamino-8-D-arginine vasopressin (DDAVP) in various bleeding disorders, 10 micrograms/m2 DDAVP was administered to subjects with von Willebrand disease (13), platelet function defects (12), von Willebrand disease and platelet defects together (8), or isolated prolongation of the bleeding time (5). DDAVP shortened the bleeding time similarly in all patient groups. Shortening of the bleeding time was also observed in 2 patients with aspirin-induced platelet defects and in 2 normal subjects. DDAVP administration was associated with falls in the platelet count, mean platelet volume, and partial thromboplastin time, and rises in platelet adhesion, factor VIII coagulant activity, factor VIII related antigen, and von Willebrand factor activity. The basal bleeding time was the only predictor of the magnitude of the bleeding-time correction. Normal haemostatis was achieved with DDAVP plus epsilon-aminocaproic acid and no blood product support during operations in 18 patients with bleeding disorders.

Adolescent↗
PubMed1984

Improved hemophilia A carrier detection by DDAVP stimulation of factor VIII.

We studied the differential increase in FVIIIc and FVIII R:Ag after the intravenous infusion of 0.30 micrograms/kg DDAVP in 20 obligate hemophilia A carriers and in 20 female controls. FVIIIc increased in carriers (59.5 +/- 23.1 to 137.5 +/- 45.9) and in controls (98.0 +/- 20.7 to 259.9 +/- 57.4) (P less than 0.001), but the magnitude of the FVIIIc increase in carriers was less than that in controls by 51.9% (P less than 0.001). FVIII R:Ag increased comparably in carriers (105.2 +/- 30.4 to 171.9 +/- 25.4) and controls (92.1 +/- 33.0 to 165.2 +/- 20.6). Using the post-DDAVP instead of the standard FVIIIc/FVIII R:Ag ratio, hemophilia carrier detection was increased from 85% (with 10% false positive and 20% false negative assignments) to 95% (with 5% false positive and 5% false negative assignments). Toxicity associated with DDAVP infusion correlated linearly with doses greater than 10.5 +/- 1.3 micrograms/m2 (P less than 0.02) and with total doses greater than 17.0 +/- 4.5 micrograms (P less than 0.02). The use of DDAVP improves carrier detection in factor VIII-deficient hemophilia.

Adolescent↗