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Biomedical subjects

J D West

Publications and source records attributed to J D West.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of preovulatory tamoxifen in regularly cycling women on folliculogenesis, oocyte recovery and luteal function.

Forty women undergoing elective sterilization and oocyte donation were randomized in a trial to study the effects of administration of 30 mg of tamoxifen 12 h before injection of human chorionic gonadotrophin and 48 h before oocyte capture. Cycles were regulated for advanced operative scheduling with norethisterone given in the luteal phase of the previous cycle and 150 mg of clomiphene given in the early follicular phase of the recovery cycle. Tamoxifen cycles showed a delay of peak urinary oestrone excretion by 2 days, associated with a slight decrease in total excretion. Tamoxifen administration lengthened treatment cycles by 0.5 days and the luteal phase by 0.4 days. The urinary excretion peak of pregnanediol was 3 days later than in controls. Total pregnanediol excretion was slightly elevated. There were no differences in oocyte recovery rate although cleavage rate was decreased (0.84 versus 0.65, not significant at P greater than or equal to 0.05). Intrafollicular oestradiol levels were similar (794 +/- 97 versus 735 +/- 102 ng/ml). Intrafollicular progesterone levels were marginally lower in tamoxifen cycles (3.5 +/- 0.5 versus 2.3 +/- 0.8 micrograms/ml).

Adult↗
PubMed1988

Chromosome anomalies in early human embryos.

A study of the chromosome constitution of an unselected group of human preimplantation embryos fertilized in vitro showed that, of 30 studied, 7 (23%) were abnormal: 6 were aneuploid, half being trisomic and half monosomic. If the increased maternal age of the oocyte donors and the lethality of autosomal monosomy is taken into account, the frequency of this kind of error is of the same order as in clinically recognized pregnancies. One oocyte had a structural abnormality. The cause of this kind of error is unknown but could be due to errors arising in spermatozoa or oocytes or the effect of environmental factors. A 'reject' group of oocytes with 3 pronuclei showed heterogeneity with respect to their chromosome complements, only one being triploid. The frequency of tripronucleate oocytes after in-vitro fertilization appears to be higher than in clinically recognized pregnancies, presumably because of the influence of superovulation on the oocytes and, under our conditions, this frequency is 9%. Therefore, if the selected and 'rejected' groups of embryos are considered together, 10 out of 33 (30%) embryos can be considered as abnormal.

Adult↗
PubMed1987

Sexing the human pre-embryo by DNA-DNA in-situ hybridisation.

Human male pre-embryos were identified by means of DNA-DNA in-situ hybridisation with a commercially available DNA probe for Y-chromosome DNA. This method could lead to prenatal diagnosis of genetic disorders based on small numbers of cells that are not necessarily in division, such as cells obtained from a pre-embryo during the course of in-vitro fertilisation therapy.

Autoradiography↗
PubMed1987

High activity of an unstable form of glucose phosphate isomerase in the mouse.

Quantitative electrophoretic studies of the three allozymes of glucose phosphate isomerase (GPI-1) produced by Gpi-1sa/Gpi-1sc heterozygous mice revealed two opposing influences on GPI-1 activity. First, the GPI-1AC heterodimer is less stable than GPI-1AA but more stable than the GPI-1CC homodimer. Second, a genetic determinant that maps close to or within the Gpi-1s structural gene causes elevated activity of GPI-1AC and probably also GPI-1CC dimers. The relative lability of these allozymes masks this elevated activity in some tissues but the effect is probably ubiquitous. The significance of these observations is discussed.

Alleles↗
PubMed1987

Post-fertilization polyploidy in human preimplantation embryos fertilized in-vitro.

The development of in-vitro fertilization (IVF) and embryo transfer (ET) as a treatment for certain forms of infertility has emphasized the need for more information on why so many preimplantation embryos fail to develop beyond the very early cleavage stages. Analysis of nuclei from embryos that had ceased to grow or that were morphologically abnormal was carried out using one of two techniques: measurement of the DNA content of their nuclei, or observation of the number of Y chromosomes per nucleus. It was found that there was a correlation between the length of time in culture and abnormal development of polyploidy in a number of the cells. On the other hand, a small proportion of polyploid cells observed in a morphologically normal expanded blastocyst probably represents the normal precursors of polyploid trophoblast cells as observed in other mammalian species.

Blastocyst↗
PubMed1987

Potential errors inherent in quantitative densitometric analysis of orthopaedic radiographs. A study after total hip arthroplasty.

We sought to determine whether x-ray densitometry could be used to provide quantitative information about the growth and resorption of bone in a retrospective analysis of the radiographs of patients who had a non-cemented hip prosthesis. We examined variables that were likely to be uncontrolled in routine orthopaedic radiographs for their effect on radiographic (film) density. Changes in film lots, exposure, target distance, field variability (heel effect), and femoral orientation were independently analyzed for radiographs of precisely oriented femora of cadavera and a radiology step-wedge. Despite attempts to normalize these variables, we found that retrospective comparison of serial radiographs of patients for densitometric analysis of change in the bone was prone to significant error. In uncontrolled radiographs, non-uniformity of exposure, intensity of the radiation field, target distance, and deviation in femoral rotation will be likely to result in substantial variations in the apparent thickness or density of the femoral cortex and make quantitative comparisons of serial radiographs unreliable.

Absorptiometry, Photon↗
PubMed1986

Investigation of the potential for mitotic recombination in the mouse.

A variation of the mouse spot test is described that is designed to distinguish between spots of altered coat colour that arise by reciprocal mitotic recombination and those caused by somatic mutation or non-disjunction. Mouse fetuses that were heterozygous for two, linked coat colour genes were irradiated (1.5 Gy X-rays) in utero at 10.25-10.50 days post coitum (p.c.) or left untreated. Subsequently, the coats were classified for the presence of spots of altered colour. The irradiated embryos were heterozygous for the linked genes pink-eyed dilution (p) and albino (c) and were produced by both the repulsion and coupling crosses. Half of the reciprocal recombination events between the centromere and the proximal marker (p), in heterozygotes with p and c in repulsion, should produce twin spots. No such twin spots would be expected from a similar event in the coupling heterozygotes. The coats of 238 irradiated and 208 untreated repulsion heterozygotes plus 107 irradiated and 314 untreated coupling heterozygotes were classified for spots. One irradiated, repulsion heterozygote had a diffuse twin spot that was only recognisable by microscopic examination of the hairs. We conclude that if the treatment described induces mitotic recombination in the mouse, it does so with low efficiency.

Animals↗
PubMed1986

Further experience of the mouse dominant cataract mutation test from an experiment with ethylnitrosourea.

6 mice with inherited cataracts and 1 new allele of microphthalmia were recovered from 923 progeny of untreated, outbred, PT stock females that had been mated to inbred C3H/HeH strain males, whose spermatogonia had been exposed to 250 mg/kg of ethylnitrosourea (ENU). The cataract phenotypes were quite variable in expression and 5/6 showed a similar range of phenotypes. 2 of the 6 mutant mice were daughters of the same ENU-treated C3H/HeH male and probably represent repeats of the same mutation. One mutation, designated lens opacity-4 (Lop-4), has been genetically mapped to the distal region of chromosome 2. The yield of 5 presumably independent cataract mutations from 923 F1 offspring is a little higher than that reported by others in similar but larger scale experiments. Approximately 3-5% of the F1 mice examined had cataracts, yet only 6/49 (12%) of these, in the experimental group, were inherited as simple Mendelian traits. We consider that this high frequency of false positives (88%), and the incomplete penetrance and variable expressivity of the cataract mutations that were found, pose serious problems that could undermine the objective nature of the dominant cataract mutation test. We suggest that further studies be made to evaluate whether the use of inbred strains would reduce the variability in the system and so make the test more objective. However, it seems likely that the high false positive rate will continue to be a serious drawback to this test system.

Animals↗
PubMed1986

Quantification of the transition from oocyte-coded to embryo-coded glucose phosphate isomerase in mouse embryos.

A quantitative electrophoretic analysis of glucose phosphate isomerase (GPI-1) allozymes produced by heterozygous Gpi-1sa/Gpi-1sb mouse embryos has enabled us to estimate separately the contributions of GPI-1 enzyme that were oocyte coded, encoded by the embryonic, maternally derived Gpi-1sa allele and encoded by the embryonic, paternally derived Gpi-1sb allele. The oocyte-coded GPI-1 activity is stable until 2 1/2 days and then declines and is exhausted by 5 1/2 to 6 1/2 days post coitum (p.c.). The maternally and paternally derived Gpi-1s alleles are probably usually activated synchronously but several possible exceptions were observed. This activation was first detected in 2 1/2-day embryos. Total GPI-1 activity falls to a minimum around 3 1/2 to 4 1/2 days, even though embryonic gene expression has already begun. The profile of oocyte-coded GPI-1 activity is consistent with the suggestion (Harper & Monk, 1983) that there is a mechanism for the removal of oocyte-coded gene products at around 2 1/2 days p.c. The method of analysis described is applicable to other dimeric enzymes with electrophoretic variants.

Animals↗
PubMed1985

Discrimination between the effects of X-ray irradiation of the mouse oocyte and uterus on the induction of dominant lethals and congenital anomalies.

In order to test whether irradiation of the postimplantation maternal environment had any effect on the apparent induction of dominant lethals or congenital anomalies by radiation, preimplantation embryos were surgically transferred between females which had been irradiated before conception or left untreated. A high proportion of preimplantation embryos, collected from females that had been irradiated 15-21 days prior to conception with 3.6 Gy X-rays, were either arrested or developmentally retarded compared with those collected from untreated females. The transfer experiments indicate that irradiation of the uterus has no significant effect on the frequency of subsequent postimplantation mortality or on mean fetal weight. However, it remains unclear whether irradiation of the uterus contributes to the induction of congenital anomalies.

Animals↗
PubMed1985

Discrimination between the effects of X-ray irradiation of the mouse oocyte and uterus on the induction of dominant lethals and congenital anomalies. II. Localised irradiation experiments.

In order to evaluate whether irradiation of the postimplantation maternal environment contributed to the induction of postimplantation mortality or congenital anomalies, mouse ovaries were surgically exteriorised and selectively irradiated or shielded in a specially constructed apparatus. The results show that exposure of the mouse abdomen and uterus to 3.70 Gy X-rays, 15-21 days prior to conception, has no significant effect on the incidence of either postimplantation mortality or congenital anomalies. Exposure of the ovaries to 3.27 Gy X-rays during the same period, however, increased the frequency of both postimplantation mortality and congenital anomalies.

Animals↗
PubMed1984

Carcinogenic effects of monofunctional and bifunctional furocoumarins.

We initiated these studies to determine whether bifunctional (interstrand cross-linking) psoralens, such as 8-methoxypsoralen (8-MOP), are more carcinogenic than are the monofunctional, such as angelicin or isopsoralen derivatives, and 3-carbethoxysporalen (3-CP). Hairless mice (Skh:hr-1) in groups of 40 were treated three times weekly for 12 to 15 months. There were 17 groups, and the photocarcinogenic effects of 5 psoralens [8-MOP, 3-CP, 5-methylangelicin, 4,5'-dimethylangelicin (4,5'-DMA), and angelicin] were investigated. Ethanolic solutions of 0.01-0.1% psoralens were topically applied at 5.0 or 50 micrograms/cm2 from cervical to lumbar regions 45 minutes before exposure to UVA (320-400 nm) radiation (0.1, 2.5, or 7.5 joules/cm2). Control groups received either the drug application or UVA exposure only. The study revealed that isopsoralens, such as 5-methylangelicin or 4,5'-DMA, that form monofunctional adducts are more carcinogenic than bifunctional psoralens. The latency and time required for 50% prevelance of tumors was much longer with 8-MOP than with 4,5'-DMA or 5-methylangelicin. Mice treated with the latter 2 compounds had a greater number and larger tumors than mice treated with 8-MOP. The monofunctional angelicin was weakly carcinogenic, whereas 3-CP, also a monofunctional psoralen, was noncarcinogenic. Histologic examination revealed that tumors induced by 8-MOP, 5-methylangelicin, or 4,5'-DMA were all squamous cell carcinomas. Because of their skin-photosensitizing property and their ability to induce interstrand cross-links and severe damage to DNA in replication, bifunctional psoralens apparently produce more lethal damage in cells than do monofunctional isopsoralens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗