Search PubMed⌕ Search

Biomedical subjects

J D West

Publications and source records attributed to J D West.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evidence for selection against tetraploid cells in tetraploid<-->diploid mouse chimaeras before the late blastocyst stage.

Tetraploid (4n) cells do not contribute equally to all tissues of midgestation mouse chimaeras and mosaics. Our previous studies of early blastocysts showed that 4n cells are preferentially allocated to the mural trophectoderm of the early blastocyst and this may contribute to the restricted distribution pattern seen at later stages. In this study of later-stage blastocysts we found evidence for selection against 4n cells. The contribution of 4n cells to 4n<-->2n chimaeric blastocysts decreased between E3.5 and E4.5 days, whereas the composition of 2n<-->2n controls changed little over this period. These results suggest that, prior to implantation, blastocysts have already lost some tetraploid cells from their embryonic and extra-embryonic lineages due to a combination of preferential allocation of 4n cells to the mural trophectoderm and selection against 4n cells throughout the embryo.

Animals↗
PubMed1997

Genetic background effects on dental and other craniofacial abnormalities in homozygous small eye (Pax6Sey/Pax6Sey) mice.

Small eye (Pax6Sey) is a semi-dominant mutation affecting development of the eyes, brain and nasal structures. The mutant phenotype arises from defects within the Pax6 gene and several mutant alleles have been identified. A previous study reported that Pax6Sey/Pax6Sey homozygotes, in a random-bred stock, had a median cartilaginous rod-like structure in the nasal region and 80% had supernumerary upper incisor teeth. In this study we show that supernumerary upper incisor teeth and a previously unreported nasal capsule-derived cartilaginous 'spur' occur in compound heterozygous Pax6Sey-Neu/Pax6Sey and homozygous Pax6Sey/Pax6Sey fetuses from several strains of mice. The frequencies of the abnormal phenotypes were not related to allele type but showed variable penetrance, which was dependent on genetic background. The median nasal cartilaginous rod-like structure was present in all homozygous small eye fetuses. The Pax6Sey/Pax6Sey homozygote may provide insight into the complex gene interactions involved in eye, nasal and craniofacial morphogenesis.

Animals↗
PubMed1997

Orthodontic-endodontic treatment planning of traumatized teeth.

Occasionally, an orthodontic patient will accidentally traumatize a maxillary anterior tooth before or during orthodontic treatment. In some situations, the trauma will be substantial and avulse the tooth. In other accidents, the tooth may not avulse, but the pulp becomes nonvital. If the pulp is devitalized, and the root has not fully formed, the apex of the root canal may be wide. In this situation, the endodontist may recommend apexification procedures to help close the apex before conventional obturation of the root canal. If the patient is currently undergoing orthodontic movement of the traumatized incisor, what effect will the tooth movement have on the success of the apexification? If the tooth were avulsed, replanted, and then ankylosed, should it be extracted? If so, when should the ankylosed incisor be removed? What effect will further facial growth have on the ankylosed tooth and the potential to achieve a successful esthetic restoration? The answers to these questions are important during the interdisciplinary treatment planning of the patient with traumatized teeth. This article will elucidate the endodontic-orthodontic considerations for patients with traumatized anterior teeth.

Adolescent↗
PubMed1997

Quantitative and spatial information on the composition of chimaeric fetal mouse eyes from single histological sections.

The spatial distribution of cells in chimaeric tissues, composed of two genotypes, provides insights into the extent of cell mixing during development and growth. However, direct measurement of patch sizes is not usually meaningful because, when the proportion of one genotype is high, a single patch may encompass several adjacent coherent clones of like genotype (clone aggregation). Two previously used methods of comparing patch lengths were evaluated to overcome this problem. The corrected mean patch length (corrected for the predicted effects of random clone aggregation) is a more useful summary statistic than the median patch length of the minor genotype, because its use is not restricted to grossly unbalanced chimaeras, but its validity has been questioned. The two methods gave almost identical numerical summaries of patch sizes in the retinal pigment epithelium of fetal chimaeras, thereby validating the use of the corrected mean patch length for this tissue. The present study also showed that the corrected patch length was unaffected by the presence of cells hemizygous for the TgN(Hbb-b1)83Clo transgene and that the proportion of pigmented cells in a single histological section was representative of the overall composition of the chimaeric fetus.

Animals↗
PubMed1997

The aesthetic and endodontic dilemmas of calcific metamorphosis.

Traumatic injuries to dentition can initiate either a resorptive or calcific pulpal response. In the sequelae of calcific degeneration, the clinical crown frequently becomes discolored, requiring an aesthetic correction to restore the tooth to its natural color. Four potential solutions are currently available to achieve this goal. The learning objective of this article is to describe the etiology of calcific metamorphosis, discuss the four potential solutions, and present the responses of endodontists polled as to the treatment indications. While the posterior dentition may experience the identical pathologic response to trauma and crown discoloration, this article focuses on the restoration of the anterior dentition. Several cases are presented to illustrate the four treatment modalities, and recommendations for follow-up of traumatic injuries are indicated.

Bicuspid↗
PubMed1996

Multiple functions for Pax6 in mouse eye and nasal development.

Mouse embryos, homozygous for the small eye (Sey) mutation die soon after birth with severe facial abnormalities that result from the failure of the eyes and nasal cavities to develop. Mutations in the Pax6 gene are responsible for the Sey phenotype. As a general disruption of eye and nasal development occurs in the homozygous Sey embryos, it is unclear, from the mutant phenotype alone, which tissues require functional Psx6. To examine the roles for Pax6 in eye and nasal development we produced chimeric mouse embryos composed of wild-type and Sey mutant cells. In these embryos we found that mutant cells were excluded from both the lens and nasal epithelium. Both of these tissues were smaller, and in some cases absent, in chimeras with high proportions of mutant cells. The morphology of the optic cup was also severely affected in these chimeras; mutant cells were excluded from the retinal pigmented epithelium and did not intermix with wild-type cells in other regions. The evidence shows that Pax6 has distinct roles in the nasal epithelium and the principal tissue components of the embryonic eye, acting directly and cell autonomously in the optic cup and lens. We suggest that Pax6 may promote cell surface changes in the optic cup and control the fate of the ectoderm from which the lens and nasal epithelia are derived.

Animals↗
PubMed1996

Genetic evidence that glycolysis is necessary for gastrulation in the mouse.

Mouse embryos homozygous for the Gpi1-sa-m1H null allele (abbreviated to m) of glucose phosphate isomerase (GPI) die early in development. A histological study was undertaken to identify the earliest abnormalities attributable to the absence of this glycolytic enzyme. Two groups of embryos were produced and examined histologically from E6.5 to E9.5 days. Experimental embryos were produced by crossing heterozygous Gpi1-sa/m females with heterozygous Gpi1-sb/m males and compared with control embryos produced by crossing heterozygous Gpi1-sb/Gpi1-sb males. The first sign of abnormality attributable to homozygous m/m embryos appeared at 7.5 days when 32.2% of the embryos in the experimental group were histologically abnormal or retarded, compared to 8.3% in the control group. The putative homozygous m/m embryos had a range of abnormalities, but consistently the egg cylinder failed to be divided into the three cavities characteristic of normal 7.5-day embryos. This suggests that a deficiency in extraembryonic mesoderm formation resulted in the failure to form the amnion or chorionic mesoderm. At 8.5 and 9.5 days the abnormal embryos from the experimental cross had progressed little further. It is suggested that in the absence of GPI, energy production is impaired so that the embryo fails to develop beyond the egg cylinder stage and gastrulation has begun completed. Developmental failure may occur before gastrulation or once gastrulation has begun and produced some mesoderm. It is concluded that glucose phosphate isomerase and presumably, therefore, glycolysis is needed for normal gastrulation of mouse embryos.

Animals↗
PubMed1996

A quantitative test for developmental neutrality of a transgenic lineage marker in mouse chimaeras.

The mouse transgene, provisionally designated TgN(Hbb-b1)83Clo, was produced by Dr C. Lo by pronuclear injection of the cloned beta-major globin gene and comprises a highly reiterated sequence that is readily detected by DNA in situ hybridization on histological sections. This fulfils many of the requirements of an ideal genetic cell marker and has been widely used for lineage studies with mouse chimaeras. However, it is not known whether it causes cell selection or influences developmental processes, such as cell mixing, in chimaeric tissues. In the present study, non-transgenic genetic markers (electrophoretic polymorphisms of glucose phosphate isomerase and differences in eye pigmentation) revealed no significant effect of the presence of hemizygous transgenic cells on the overall composition, size or gross morphology of 12 1/2 d chimaeric foetuses, placentas or extraembryonic membranes. Also, a previously described maternal genetic effect on the composition of chimaeric tissues occurred in the presence or absence of the transgene. These tests have demonstrated that hemizygous cells are not at a significant selective disadvantage, when incorporated into mouse aggregation chimaeras with non-transgenic cells. Further studies are needed to test whether homozygous transgenic cells are also selectively neutral and to test whether hemizygous or homozygous transgenic cells influence developmental processes, such as cell mixing, that were not tested.

Animals↗
PubMed1996

The influence of ploidy on the distribution of cells in chimaeric mouse blastocysts.

Previous studies of tetraploid<-->diploid mouse chimaeras and mosaics have revealed that tetraploid cells do not contribute equally to all tissues of the conceptus. In this study we have shown that, within 30 h of aggregating cleavage stage embryos, tetraploid cells were non-randomly distributed among different tissues of the early blastocyst. They were preferentially allocated to the mural trophectoderm regardless of cell size at the time of aggregation. This early effect may underlie the restricted distribution of tetraploid cells at later stages. We have demonstrated for the first time that ploidy can influence the relative position of blastomeres in the preimplantation embryo.

Animals↗
PubMed1995

Restricted distribution of tetraploid cells in mouse tetraploid<==>diploid chimaeras.

Tetraploid mouse embryos were produced by electrofusion at the 2-cell stage, cultured overnight, and aggregated with normal diploid embryos to produce tetraploid<==>diploid (4n<==>2n) chimaeric conceptuses. At 7 1/2 days the 4n<==>2n chimaeras were usually smaller and developmentally retarded compared to control diploid<==>diploid chimaeras. At 12 1/2 days the 4n<==>2n chimaeras had heavier placentas but there was no significant difference in fetal size. Tetraploid cells showed a restricted tissue distribution at both developmental stages studied: 4n cells were commonly present in both the primitive endoderm and the trophectoderm lineages but they rarely contributed to the primitive ectoderm lineage. The overall similarity in the distribution of tetraploid cells at 7 1/2 and 12 1/2 days implies that whatever causes the restricted tissue distribution operates largely before 7 1/2 days. There was no evidence for excessive embryonic losses of 4n<==>2n chimaeras. So, if the restricted distribution of 4n cells was a result of cell selection, the mechanism is more likely to involve loss of 4n cells from the primitive ectoderm early in development rather than selective death of conceptuses with tetraploid cells in this lineage. Alternatively, 4n cells may be preferentially allocated to the trophectoderm and primitive endoderm rather than the primitive ectoderm layer at the blastocyst stage.

Animals↗
PubMed1995

Biochemical evidence for cell fusion in placentas of mouse aggregation chimeras.

Eight series of mouse chimeras were produced by aggregating 8-cell embryos that differed at the Gpi-1s locus, encoding glucose phosphate isomerase (GPI-1). Chimeric blastocysts (Gpi-1sa/Gpi-1sa <--> Gpi-1sb/Gpi-1sb) were transferred to pseudopregnant females, which produced only GPI-1C enzyme. Quantitative electrophoresis of GPI-1 was used to estimate the contribution of each embryo (GPI-1A and GPI-1B enzyme activity) to the fetus and placentas of 12 1/2 day chimeric conceptuses. Chimeric fetuses and placentas were identified by the presence of both GPI-1AA and GPI-1BB homodimers. The overall distribution of the percentage GPI-1A in the placentas was bimodal or U-shaped. It was positively correlated with the %GPI-1A in the fetus in most of the eight series of chimeras analyzed. In the first chimera experiment, involving seven series of chimeras, GPI-1AB heteropolymer was detected in 78/211 (37%) of the placentas. Heteropolymer was not detected in chimeric placentas with an unbalanced composition of GPI-1A and GPI-1B. The production of heteropolymer implies that GPI-1A and GPI-1B monomers are produced in the same cell and that fusion must have occurred between the two genetically distinct cell populations in the placenta. In the second experiment, samples of different regions were dissected from another series of 27 chimeric placentas and analyzed; 12 contained heteropolymer. Although GPI-1AB heteropolymer was widely distributed throughout the placenta it was detected less frequently in the outer part of the placenta. In another experiment, analysis of 34 homozygous (nonchimeric) Gpi-1sb/Gpi-1sb conceptuses transferred to homozygous Gpi-1sa/Gpi-1sa reproductive tracts revealed no evidence for fusion between maternal cells and cells of zygotic origin in the placenta. The chimera studies provide biochemical evidence for fusion between zygotic cells in the murine placenta. This presumably occurs during the formation of the syncytial trophoblast.

Animals↗
PubMed1995

A maternal genetic effect on the composition of mouse aggregation chimaeras.

Two series of 12 1/2 day mouse chimaeric conceptuses were produced by aggregating (C57BL x CBA)F2 strain preimplantation embryos with embryos that differed at the Gpi-1s locus that encodes glucose phosphate isomerase, GPI-1. The composition of individual issues was evaluated by quantitative electrophoresis to estimate the % GPI-1A in the chimaeric tissue containing GPI-1A and GPI-1B. In one series of chimaeras, the GPI-1A cells were derived from a backcross between inbred BALB/c strain females and (BC x BALB/c)F1 males, where BC is the partly congenic strain C57BL/Ola.AKR-Gpi-lsa,c/Ws. In the other series of chimaeras, the GPI-1A cells were derived from the reciprocal backcross between (BC x BALB/c)F1 females and inbred BALB/c strain males. The [(BC x BALB/c)F1 female x BALB/c male]<==>(C57BL x CBA)F2 series of chimaeras was reasonably balanced so that GPI-1A and GPI-1B cells were fairly equally represented in the foetuses, placentas and extraembryonic membranes (tissue means: 37-51% GPI-1A). This series did not differ significantly in composition from an earlier series of (BC x BALB/c)F2<==>(C57BL x CBA)F2 chimaeras. However, the [BALB/c female x (BC x BALB/c)F1 male]<==>(C57BL x CBA)F2 series of chimaeras was unbalanced, with mean tissue compositions (28-33% GPI-1A) that were intermediate between the above two balanced series and the unbalanced (BALB/c x BALB/c)<==>(C57BL x CBA)F2 series (tissue means: 14-22% GPI-1A), that was studied previously. Thus, both (BALB/c x BALB/c) and [BALB/c x (BC x BALB/c)F1] embryos contributed less to the tissues of chimaeric conceptuses than either (BC x BALB/c)F2 or [BC x BALB/c)F1 x BALB/c] embryos. This implies that embryos from BALB/c mothers contributed less to the tissues of chimaeric conceptuses than embryos from (BC x BALB/c)F1 mothers. We, therefore, conclude that a maternal genetic effect is responsible for some of the differences in composition among the four groups of chimaeras. This maternal effect must act before the 8-cell stage but it is not yet known whether it is mediated via cytoplasmic inheritance, genomic imprinting or by the reproductive tract. Evidence that a maternal effect retards preimplantation development of embryos from BALB/c females is reviewed and the possibility that this might cause them to contribute poorly to chimaeric conceptuses when aggregated with more precociously developing embryos is discussed.

Alleles↗
PubMed1994

A chimaeric animal model for confined placental mosaicism.

The reason for chromosome mosaicism being sometimes confined to only part of the conceptus is unknown. To address this problem, we produced tetraploid<-->diploid chimaeric mouse conceptuses. At 12 1/2 days, no tetraploid cells were detected in the fetus. They rarely contributed to other derivatives of the primitive ectoderm lineage but were commonly found in the primitive endoderm and trophectoderm lineages. This provides a useful animal model of human confined placental mosaicism and suggests that the primitive endoderm (hypoblast) lineage should be included in future studies of human mosaic conceptuses.

Aneuploidy↗
PubMed1994

A method to determine the location and shape of an intracoronal bleach barrier.

The external cervical root resorption associated with intracoronal bleaching of pulpless teeth can be a devastating lesion. It often cannot be repaired. To prevent this problem, increasing attention has been focused on placing a barrier between the pulp chamber and the endodontic filling material. The objective of this article is to propose a method for determining the location and shape of an intracoronal bleach barrier.

Dental Pulp Devitalization↗
PubMed1994

Genotypically unbalanced diploid<==>diploid foetal mouse chimaeras: possible relevance to human confined mosaicism.

Two series of mouse chimaeras were produced by aggregating pairs of eight-cell embryos that differed at the Gpi-1s locus, encoding glucose phosphate isomerase (GPI-1); the paired embryos were respectively homozygous Gpi-1sa/Gpi-1sa and Gpi-1sb/Gpi-1sb. Chimaeric blastocysts were transferred to pseudopregnant females, that were homozygous Gpi-1sc/Gpi-1sc and produced only GPI-1C enzyme. Quantitative electrophoresis of GPI-1 was used to estimate the contribution of each embryo (GPI-1A and GPI-1B enzyme activity) to the foetus, placenta and other extraembryonic tissues of 12 1/2 day chimaeric conceptuses. For both series of chimaeras, the distributions of %GPI-1A in different tissues were classified as (1) balanced and typical, (2) balanced but atypical or (3) unbalanced. One series of chimaeras was clearly unbalanced, so that the cells derived from the (C57BL x CBA/Ca)F2 embryo (Gpi-1sb/Gpi-1sb) predominated over those derived from the BALB/c inbred strain (Gpi-1sa/Gpi-1sa) in most foetuses. Two significant observations were made concerning this unbalanced series. Firstly, the mean composition of the placenta and other extraembryonic tissues was similar to that in the foetus, i.e. also unbalanced with (C57BL x CBA/Ca)F2 (abbreviated to BF2) cells predominating. Secondly, despite this generalized deficiency of BALB/c cells, there were differences in the frequency of non-chimaeric tissues between different developmental lineages. In 20/38 [corrected] chimaeric conceptuses in the unbalanced series only BF2 cells were detected in the foetus, whereas both BF2 and BALB/c cells were present in at least one of the extraembryonic tissues. This group of chimaeras, therefore, shows some similarities to human confined mosaicism. Although chimaerism occurred more often in the primitive endoderm (hypoblast) lineage (yolk sac endoderm and parietal endoderm) than in the placenta, this may also be the case in human mosaics. The mosaic status of the human yolk sac endoderm is usually unknown so it is possible that mosaicism often occurs in the yolk sac endoderm as well as the trophectoderm in human 'confined placental mosaicism'. The uniformly unbalanced phenotype seen in the mouse chimaeras may be a result of generalized cell selection against BALB/c cells in all tissues. As an alternative explanation, we propose that most of the BALB/c cells in the blastocyst are allocated to the mural trophectoderm, which has a limited mitotic potential and so contributes little to the mid-gestation conceptus. Further work is required to test these possibilities.

Albinism, Ocular↗
PubMed1994

The relationship of initial embryo crown--rump length to pregnancy outcome and abortus karyotype based on new growth curves for the 2-31 mm embryo.

The objective of this study was to determine if measurement of initial crown--rump length (CRL) is helpful in predicting low birth weight, newborn length, spontaneous abortions, or abortus karyotype. We measured CRL prospectively in 837 consecutive singleton pregnancies at the time a heart rate was first detectable with transvaginal ultrasonography and compared these measurements to normal values for the 10th through 90th centiles determined from 227 transvaginal ultrasound measurements in in-vitro fertilization and gamete intra-Fallopian transfer pregnancies with known ovulation dates. The relationship of initial CRL to birth weight and length and to abortion and abortus karyotype was analysed after all pregnancies had delivered. Initial CRL measured after the 28th post-ovulation day was predictive of subsequent abortion, but not of low birth weight or length. The abortion rate was 3.3% [95% confidence interval (CI) 1.5%, 5.1%] when initial CRL > or = 50th centile, compared to 19.4% (95% CI 15.4%, 23.4%) when < 50th centile. Initial CRL was < 50th centile in 13 out of 14 trisomic and in eight out of 10 other karyotypically abnormal aborti. These results indicate that initial CRL measured after the 28th post-ovulation day may help to identify pregnancies at increased risk of abortion due to abnormal karyotypes.

Abortion, Spontaneous↗
PubMed1994

Lack of association between maternal phosphoglucomutase-1 phenotype and fetal macrosomia in diabetic pregnancy.

OBJECTIVE: To assess the reports that maternal phosphoglucomutase-1 (PGM1) phenotype is highly related to macrosomia in diabetic pregnancy. This could be either a direct metabolic phenomenon, or the PGM1 locus could be a marker for a tightly linked gene involved in the maternal control of fetal growth. DESIGN: A comparative biochemical genetic study. SETTING: A large diabetic pregnancy clinic. SUBJECTS: One hundred and fifty-two women who had diabetes during pregnancy, 136 being insulin dependent before pregnancy. Two hundred and thirty-six women without pre-existing medical or pregnancy complications who functioned as a control group. MEASURES: PGM1 phenotype was assessed by conventional electrophoresis and subgroups were examined using iso-electric focusing. OUTCOME: Standardised birthweight was corrected for sex, maternal parity and gestation confirmed in every case by early pregnancy ultrasound. Maternal diabetes control was assessed by glycosylated haemoglobin. RESULTS: No differences were found in the observed phenotype frequencies for diabetics and control pregnant women. No association between PGM1 phenotype and macrosomia in diabetic pregnancy was found. PGM1 did not make a significant contribution to birthweight, standardised birthweight, length or ponderal index of the baby as assessed by multiple regression. CONCLUSIONS: Our study of a larger number of insulin dependent diabetics in Scotland makes the claim that macrosomia in diabetic pregnancy is associated with PGM1 phenotype unlikely to be of general significance.

Analysis of Variance↗