PubMed Health⌕ Search

Biomedical subjects

A McLaren

Publications and source records attributed to A McLaren.

At least 19 recordsLinked to original sources
PubMed1992

Recombination between the X and Y chromosomes and the Sxr region of the mouse.

The Sxr (sex-reversed) region that carries a copy of the mouse Y chromosomal testis-determining gene can be attached to the distal end of either the Y or the X chromosome. During male meiosis, Sxr recombined freely between the X and Y chromosomes, with an estimated recombination frequency not significantly different from 50% in either direction. During female meiosis, Sxr recombined freely between the X chromosome to which it was attached and an X-autosome translocation. A male mouse carrying the original Sxra region on its Y chromosome, and the shorter Sxrb variant on the X, also showed 50% recombination between the sex chromosomes. Evidence of unequal crossing-over between the two Sxr regions was obtained: using five markers deleted from Sxrb, 3 variant Sxr regions were detected in 159 progeny (1.9%). Four other variants (one from the original cross and three from later generations) were presumed to have been derived from illegitimate pairing and crossing-over between Sxrb and the homologous region on the short arm of the Y chromosome. The generation of new variants throws light on the arrangement of gene loci and other markers within the short arm of the mouse Y chromosome.

Animals↗
PubMed1991

Development of the mammalian gonad: the fate of the supporting cell lineage.

Sex determination in mammals is mediated via the supporting cell lineage in the fetal gonad. In the very early stages of gonadal development, the fate of the supporting cell population is critically dependent on the expression of the male-determining gene on the Y chromosome. If this gene is absent or fails to be expressed, or is expressed too late or in too small a number of supporting cells, all supporting cells (XX or XY) differentiate as pre-follicle cells and development proceeds along the female pathway. Supporting cells in which the male-determining gene is expressed in a timely manner differentiate as pre-Sertoli cells; given sufficient such cells, testis cords form and development proceeds in a male direction. If XX supporting cells are also present, a few may be recruited into the pre-Sertoli population and participate in testis cord formation. The subsequent fate of pre-follicle cells depends critically on interaction with the germ cell population in the developing gonad: absence of germ cells may lead to partial masculinization of the gonad, and/or to disappearance of the supporting cell component.

Animals↗
PubMed1991

Variable spread of X inactivation affecting the expression of different epitopes of the Hya gene product in mouse B-cell clones.

Cloned B-cell lines from a female T16H/XSxr mouse in which Tdy expression was suppressed due to X inactivation and from a male X/XSxr mouse, both of the (kxb)F1 haplotype, were examined for H-Y expression. This was determined both by their ability to act as targets for H-2k and H-2b-restricted H-Y-specific cytotoxic T cells and by their ability to stimulate the proliferation of H-2Kk, H-2Db (class I) and Ab (class II)-restricted T-cell clones. In B-cell clones from the T16H/XSxr mouse, expression of H-Y/Db exhibited partial X inactivation and only a proportion (congruent to 30%) of the cells were targets for or stimulated H-2Db-restricted H-Y-specific T cells. In contrast, H-Y epitopes restricted by H-2k (H-Y/Kk, H-Y/Dk) and Ab (H-Y/Ab) exhibited no X inactivation. Furthermore, no inactivation of H-Y/Db, H-Y/Ab, or H-Yk was observed in the male X/XSxr mouse. These results indicate that the T16H/XSxr female is a mosaic, as a result of the variable spread of X inactivation into the Sxr region. They further suggest that the H-Y antigen recognized in association with H-2k and H-2Db class I molecules and Ab class II molecules may be the product of more than one gene.

Animals↗
PubMed1991

Male antigen defined serologically does not identify a factor responsible for testicular development.

To test the proposal that the serologically detected male antigen (SDMA; which may or may not be the same as H-Y) was responsible for triggering the indifferent gonad to differentiate into the testis in mammals, H-Y negative sex-reversed XXSxr' male mice were investigated for the presence of SDMA. Serum from C57BL/6 female mice immunized against tissue from XXSxr' males did not contain SDMA specific antibody as detected by the complement-mediated sperm cytotoxicity assay. Thus, although SDMA is a male-specific factor and may play a role in male sex determination, it does not identify the testis-determining factor (TDF).

Animals↗
PubMed1991

CD5-T lymphocytes in renal transplant recipients.

The CD3+CD5--subpopulation of T cells has been shown to be increased in patients following allogeneic bone marrow transplantation, and a statistical association has been found with graft-versus-host disease (GVHD). We studied this population in renal transplant recipients. There was no correlation with rejection episodes but we found an increase in this CD3+CD5--population in patients on cyclosporin, and we suggest that these cells may be involved in the mechanism of action of this drug. In patients on azathioprine the absolute number of CD3+CD5--lymphocytes is reduced, along with other lymphoid subpopulations.

Antigens, CD↗
PubMed1991

Recovery of CD3+ and CD5- lymphocyte subpopulation after autologous bone marrow transplantation and chemotherapy.

Although most circulating T cells in normal subjects express both CD3 and CD5 antigens on the cell surface, a small number lack the CD5 antigen. Recipients of allogeneic bone marrow transplants develop increased numbers of CD3+ CD5- cells, particularly those who develop graft versus host disease (GVHD). This CD3+ CD5- population may rise transiently in patients who have received an autologous bone marrow transplant (BMT) and in patients following completion of intensive chemotherapy for acute myeloid leukaemia (AML). These findings suggest that these CD3+ CD5- cells are a normal component of the regenerating lymphoid system after BMT or chemotherapy.

Acute Disease↗
PubMed1990

A mouse zinc finger gene which is transiently expressed during spermatogenesis.

Zinc finger proteins are polypeptides with sequence-specific, nucleic acid-binding properties. Substantial evidence has established them as a class of trans-acting molecules with regulatory roles in cellular growth and differentiation. We have screened an 11.5 day post coitum urogenital ridge cDNA library with an oligonucleotide encoding a sequence conserved between a variety of zinc finger proteins. By cDNA cloning and sequencing we show that a novel mouse gene, Zfp-35, encodes a protein with a block of 18 zinc finger domains and an N-terminal region rich in acidic residues. The 2.4 kb mRNA encoding this polypeptide is selectively expressed in adult testis, by comparison with other organs. We have analysed Zfp-35 expression in whole testes of sex-reversed mice, whole testes of prepuberal XY animals, germ cell fractions from XY adult testes and by in situ hybridization to sections from adult XY testes. Our studies show that a considerable increase in expression is restricted to spermatocytes at the pachytene stage of meiotic prophase. These experiments suggest that Zfp-35 may act to control gene activity during this particular stage of spermatogenesis.

Amino Acid Sequence↗
PubMed1990

Dysprosium (165Dy) hydroxide macroaggregates for radiation synovectomy--animal studies.

This paper reports the development of a new chemical formulation, Dy-HMA, to utilise the advantages of dysprosium 165 in radiation synovectomy of certain forms of arthritis. Dy-HMA is a sterile suspension of dysprosium hydroxide macroaggregates (approximately 6 mg Dy/ml) in saline with the majority of particles in the 3-5 microns range. The absence of ferric hydroxide and a higher concentration of dysprosium in the formulation offer advantages over dysprosium ferric hydroxide macroaggregates, Dy-165-FHMA. Biodistribution studies in rats and rabbits with Dy-HMA show less leakage than with Dy-FHMA and considerably less leakage than with yttrium silicate colloid. Rabbits treated with intra-articular injections of Dy-HMA equivalent to 10-30 times the typical clinical dose showed no signs of any toxic effects.

Animals↗
PubMed1990

Development of mouse germ cells in cultures of fetal gonads.

Mouse gonadal tissue was studied under various conditions of in vitro culture, with the aim of clarifying some of the somatic-cell influences that regulate the development of germ cells in the mammalian gonad. Gonadal ridges, with or without the adjacent mesonephric region, were removed from mouse embryos 10.5-12.5 days post coitum (dpc). In an organ culture system, the female ridges showed good development, with no masculinization. All germ cells entered meiosis at the expected time. Although some oocytes entered the growth phase, many primordial follicles were observed. 11.5- and 12.5-day male ridges formed testis cords, and the germ cells developed as T-prospermatogonia. In 10.5-day ridges, cells resembling Sertoli cells differentiated but did not form testis cords, and the germ cells entered meiosis. We conclude that full differentiation of the supporting cell lineage was not achieved when culture was begun at 10.5 dpc; our findings suggest that immature Sertoli cells neither form testis cords nor inhibit the entry of germ cells into meiosis. When the ridges were fragmented and cultured in gas-permeable dishes, the somatic cells grew out as a monolayer on which the germ cells rested. Under these conditions male germ cells did not enter meiosis and did not survive for more than a few days. Female germ cells entered meiosis. In contrast to the organ culture system, many of the surviving oocytes entered the growth phase during the second week of culture, reaching diameters of up to 60 microns. This suggests that normal follicular cell investment may play a crucial role in maintaining the oocyte in a state of developmental arrest. The growing oocytes showed the oocyte-specific expression of the enzyme glucose phosphate isomerase. It seems that the initiation and maintenance of both oocyte growth and oocyte-specific gene expression can take place in the absence of normal follicular cell investment.

Animals↗
PubMed1990

Primordial germ cells in the mouse embryo during gastrulation.

With the aid of a whole-mount technique, we have detected a small cluster of alkaline phosphatase (ALP)-positive cells in whole mounts of mid-primitive-streak-stage embryos, 7-7 1/4 days post coitum (dpc). Within the cluster, about 8 cells contain a small cytoplasmic spot, intensely stained for ALP activity and possibly associated with an active Golgi complex. The cluster lies just posterior to the definitive primitive streak in the extraembryonic mesoderm, separated from the embryo by the amniotic fold. Towards the end of gastrulation, the number of cells containing the ALP-positive spot rises to between 50 and 80. Thereafter the number of cells in the extraembryonic cluster declines, and similar cells start to be seen in the mesoderm of the primitive streak and then in the endoderm. At 8 dpc, about 125 ALP-stained cells are found, mainly in the hindgut endoderm and also at the base of the allantois, their appearance and location at this stage agreeing closely with previous reports on primordial germ cells (PGCs). Embryos from which the cluster area has been removed at the 7-day stage are devoid of PGCs after culture for 48 h, whereas the excised tissue is rich in PGCs. We argue that the cells in the cluster are indeed primordial germ cells, at a stage significantly earlier than any reported previously. This would indicate that the PGC lineage in the mouse is set aside at least as early as 7 dpc, possibly as one of the first 'mesodermal' cell types to emerge, and that its differentiation, as expressed by ALP activity, is gradual.

Alkaline Phosphatase↗