Biomedical subjects

P Dockery

Publications and source records attributed to P Dockery.

48 records · Page 3Linked to original sources

PubMed1989

The endometrial cycle: the expression of a secretory component correlated with the luteinizing hormone peak.

This paper reports the pattern of production and secretion of a secretory phase epitope in the endometrium of 44 normal fertile women. Peroxidase immunochemistry was used to detect the monoclonal antibody D9B1, which binds to a peptide-associated sialylated oligosaccharide, in endometrial biopsies all chronologically dated from the luteinizing hormone (LH) peak. During the proliferative phase, the epitope was shown to be absent from tissue sections. It first made its appearance within gland cells 2 days after the LH peak. By LH+3 a rapid accumulation of the D9B1 epitope was noted in the base of the cell, below the nucleus. On subsequent days, increasing amounts of the antigen were detected in the apical cytoplasm, apparently in a more concentrated form than in the basal cell zone. On day LH+6, around the time of implantation, secretory vesicles in the cell apex were discharged into the gland lumen where the glycoconjugate finally accumulated. This immunohistochemical approach introduces a new parameter for evaluation of endometrial function and could be used to improve the accuracy of histological assessment of the endometrial cycle.

Adolescent↗

PubMed1989

The relation between daily salivary progesterone profile and endometrial development in the luteal phase of fertile and infertile women.

This study analysed the relation between daily salivary progesterone profiles in the luteal phase and endometrial development as assessed by morphometric studies of endometrial biopsies that were timed by luteinizing hormone surge. Among 34 fertile women studied, a threshold relation was noted between cumulative salivary progesterone concentration and 11 of the 17 morphometric features measured, as well as the results of the histological dating. Above the observed threshold, a significant linear correlation was found between cumulative salivary progesterone and the results of histological dating. Among 55 women, progesterone profile in the first half of the luteal phase, but not the second half, was found to be significantly lower in those with retarded endometrial development than in those with normal development. Overall, 50% of retarded endometrial development was associated with a subnormal progesterone profile, but the other 50% was associated with a normal progesterone profile, in keeping with an abnormal response of the endometrium due to progesterone receptor deficiency. Retarded endometrial development was more likely to be associated with a subnormal progesterone profile in the first half of the luteal phase than in the second half.

Adult↗

PubMed1988

Why does RU486 fail to prevent implantation despite success in inducing menstruation?

The administration of RU38486 (RU486) in the luteal phase may induce menstruation, but it may not be associated with shedding of the functional layer of the endometrium. This provides an explanation why, in some cases of successful menstrual induction by RU486, pregnancy continues undisturbed. The ability of RU486 to interrupt a very early pregnancy is more likely to be related to its ability to cause shedding of the endometrium than its ability to induce menstruation.

Adult↗

PubMed1988

A new method of histologic dating of human endometrium in the luteal phase.

Morphometric analysis was performed on 70 endometrial biopsy specimens collected from a population of fertile women. Of the 17 morphometric measurements that were performed on each endometrial biopsy, only 5 were required to achieve a highly significant correlation with chronologic dating based on luteinizing hormone surge (R = 0.99). The result of histologic dating, based on morphometric analysis of endometrial biopsies collected from a separate, unbiased population, correlated strongly and significantly with chronologic dating (r = 0.98, P less than 0.0001). The correlation was better than that achieved when histologic dating was performed according to the conventional dating criteria (r = 0.88, P less than 0.001).

Endometrium↗

PubMed1988

The effects of progesterone receptor blockade in the luteal phase of normal fertile women.

The effects of a single, variable dose (5 to 200 mg) of RU38486 (RU486) (Roussel-Uclaf, Paris, France) in the first half of the luteal phase of the menstrual cycle were studied in 30 normal fertile volunteers. Quantitative histologic techniques were employed, and the results were compared with normal ranges derived from a separate, normal, fertile population. It was found that RU486 inhibited glandular secretory activity, accelerated degenerative changes, induced various vascular changes, increased stromal but not glandular mitotic activity, and did not affect the predecidual reaction. The superiority of morphometric analysis over traditional dating criteria was demonstrated in this study of endometrial responses to an exogenously administered agent. In addition, it was found that temperature drop occurred in 56%, menstrual induction in 43%, luteolysis in 24%, mood change in 23%, and thirst sensation in 3% of women studied. Both menstrual induction and changes in hypothalamic function after the administration of RU486 occurred independently of luteolysis and so were likely to be the direct result of progesterone receptor blockade in these organs. Menstrual induction was significantly related to the dose given and the day on which RU486 was administered. Mood change was significantly related to the day on which RU486 was given. Most of the effects of RU486 occurred around 48 hours after its administration.

Adolescent↗

PubMed1988

An examination of the variation in timed endometrial biopsies.

Endometrial biopsies were obtained from fertile women, aged 20-40 years, with regular cycles of 25-35 days. Chronological dating of the material was carried out by determination of the luteinizing hormone (LH) peak by daily LH assay. Tissue was taken from three or four sites along the biopsy and processed for electron microscopy. Half micron thick sections were analysed by light microscopy and a morphometric examination of the glandular epithelium carried out. Nuclear size was assessed using an unbiased measuring technique and the volume density of the nucleus in the cell was also measured. A series of 12 women was examined, four at each of days LH + 2, 4 and 5. An attempt was made to control a variety of factors which contribute to the variability in the histological dating of the endometrial biopsy. In doing so it was possible to analyse the relative contributions of each sampling level to the overall variance. In contrast to earlier studies there is a relatively small intersubject variation with a correspondingly large within-biopsy variation. These results may indicate that the cellular events in the glandular epithelium, between ovulation and the middle of the luteal phase, are precisely regulated.

Adult↗

PubMed1988

The ultrastructure of the glandular epithelium in the timed endometrial biopsy.

This paper reports the electron microscopic appearance of the uterine glandular epithelium in a group of 25 women of known fertility who underwent endometrial biopsies at known times after the luteinizing hormone (LH) surge between LH + 2 and LH + 6. The use of these well-timed endometrial biopsies enables one to gain a clearer insight into the cellular dynamics of the glandular cells, between ovulation and the middle of the luteal phase. Under the influence of progesterone, the cells are transformed from relatively inactive cells full of free ribosomes to very active polarized cells, containing giant mitochondrial profiles, intracellular deposits of glycogen/glycoprotein-rich material and a complex intranuclear channel system. Intimate associations between organelles develop, the most notable being that between a semi-rough endoplasmic reticulum and the mitochondria. By taking biopsies that are accurately timed, relative to the LH surge, from a group of women of known fertility, the sequences of changes in ultrastructure are established with considerably more precision than was previously available.

Adult↗

PubMed1987

A comparison between two methods of chronological dating of human endometrial biopsies during the luteal phase, and their correlation with histologic dating.

This prospective study was performed on 61 infertile women to examine the correlation between histologic dating using the same criteria by two independent observers and chronological dating by two different methods: (1) determination of luteinizing hormone (LH) peak by daily LH assay, (2) calculation based on the onset of the next menstrual period (NMP). The correlation between histologic dating and chronological dating was found to be significantly better if the LH peak was used to determine the chronological date than if the NMP was used (r = 0.70 and 0.37, respectively).

Biopsy↗

PubMed1983

Peripheral nerve abnormalities in the diabetic mutant mouse.

Observations were made on the genetically diabetic C57BL/Ks (db/db) mouse. Morphometric observations were performed on the tibial nerve at 6, 9, and 15 mo and compared with those from nondiabetic (m/m) controls. Myelinated fiber size was less in the diabetic animals at all stages and affected cross-sectional axon area and myelin thickness equally. Unmyelinated axons were unaffected. The index of circularity of myelinated axons did not differ between diabetic and control animals. No definite absolute reduction in fiber size occurred and degenerative changes, which were slight, were equally frequent in the diabetic and control nerves. Axonal glycogenosomes, polyglucosan particles, and Schwann cell/axon networks, and Schwann cell Reich granules increased with age in both groups, but only glycogenosomes were consistently more numerous in the diabetic animals. Counts of membrane associated particles in both P and E faces revealed that these were reduced in number in the diabetic animals in myelin and in axolemma of unmyelinated axons, but not in the axolemma of myelinated fibers. Growth in tibial length was also reduced in the diabetic animals and this suggested that the reduced fiber diameter probably represented a maturational deficit. The absence of a selective reduction in axonal size did not favor a primary axonopathy as the cause.

Animals↗

PubMedDate not supplied

Changes in basement membrane thickness in the human endometrium during the luteal phase of the menstrual cycle.

We have examined aspects of the fine structure of the basal laminae associated with the luminal and glandular epithelium and small blood vessels in the human endometrium. Four short studies are presented and reviewed. Study 1 examined biopsies from 20 fertile women taken on days after the luteinizing hormone surge (LH): LH +2, 4, 6, 8 and 10. The basal lamina (both lamina densa and lucida) increased in thickness over the period studied. Study 2 again studied the glandular epithelium and examined the effect of RU486 (a progesterone receptor blocker) administered on day LH +3 and biopsied on day LH +6. The basal laminae were found to be the same as LH +2 control group but thinner than LH +6 control. Study 3 documented increased thickness of the basal laminae between LH +6, 8 and 13 in the luminal epithelium. The within-group coefficient of variation was 16% and 27% for LH +6 and LH +13 groups but only 2 % for LH +8. Study 4 demonstrated an increase in basal lamina thickness associated with small blood vessels between LH +6 and LH +10 in normal fertile women. The basal lamina provides the interface between epithelial and mesenchymal environments; changes in its structure can alter the phenotypic expression of the epithelia. It is one of the maternal barriers that must be transgressed by the trophoblast during implantation. Together, these combined studies provide quantitative baseline structural information on the electron microscopical appearance of the basal lamina during the luteal phase of the menstrual cycle.

Basement Membrane↗

PubMedDate not supplied

Innervation of accessory sex glands in the adult male golden hamster and quantitative changes of nerve densities with age.

Enzyme histochemistry and immunohistochemistry were used to determine the types of nerves supplying the ampullary gland, coagulating gland, dorsolateral prostate, ventral prostate and seminal vesicle of the male golden hamster. Quantitative change of dopamine beta-hydroxylase (DbetaH), and neuropeptide Y (NPY) immunoreactive and acetylcholinesterase-stained (AChE-stained) nerves with age was also determined. Using an antibody against protein gene product 9.5, nerves were seen to distribute in subepithelial connective tissues, smooth muscles and adventitial connective tissues. Presumptive catecholaminergic nerves immunoreactive for DbetaH and tyrosine hydroxylase were found mainly in periacinar smooth muscles, while AChE-stained nerves predominantly ramified subepithelial connective tissues. In addition, nerves immunoreactive to NPY, calcitonin gene-related peptide, leu-enkephalin, galanin, substance P, and vasoactive intestinal peptide were also detected. Quantitative estimation at 10, 52 and 78 weeks of age showed that densities of DbetaH and NPY nerves were halved by 52 weeks of age. This level was maintained in older animals. The density of AChE-stained nerves in all glands did not change with age. The ampullary gland appeared to have more AChE-stained nerves. These results were discussed from a comparative viewpoint and with regard to possible implications of aging of peripheral nerves on functioning of the male accessory sex glands.

Aging↗

PubMedDate not supplied

Application of the new stereological probes to the study of the melanosome in Cloudman S91 melanoma cells.

The relationship between melanosome size and number and melanin content has been investigated in Cloudman S91 melanoma cells growing in vitro using both "model-based" and "design-based" stereological procedures. Cells were cultured for 4 days, harvested at daily intervals, and resin-embedded for light and electron microscopy; one aliquot of each sample of cells was assayed to determine its melanin content. By comparing their volume-weighted mean nuclear volume and their number-weighted mean nuclear volume, we have found that the nuclei of Cloudman melanoma cells form a fairly homogeneous population. The volume fraction and absolute volume of premelanosomes (VVpm, cell and Vpm) and mature melanosomes (VVmm, cell and Vmm) were all found to decrease progressively throughout the period of culture as did the number of premelanosomes (Npm) and mature melanosomes (Nmm). Whilst the volume-weighted mean volume of individual stage I and stage II premelanosomes, (VVipm), remained fairly constant at about 10 nm3, the volume of individual stage III and IV mature melanosomes showed significant variation ranging between about 13 nm3 and 32 nm3. The melanin content of the cells decreased progressively over the 4 days of culture. There were, however, considerable variations in both the average melanin content per unit volume of mature melanosomes, in the range 170-600 fg/micron3, and in the melanin content per individual mature melanosome, in the range 3-12 fg. Our findings show that stereological techniques can provide unbiased and sensitive tools for the study of the morphological basis of melanogenesis; their value will become even more evident when they are combined with techniques for the localization of melanogenic enzymes and their substrates.

Cell Count↗