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Biomedical subjects

N J Walker

Publications and source records attributed to N J Walker.

53 records · Page 3Linked to original sources
PubMed1990

Ultrastructure of murine trisomy 1 optic cup.

The optic cups of two gestational day 11 trisomy (ts) 1 mouse embryos and a normal littermate control were examined using transmission electron microscopy (TEM). One trisomic embryo had a small lens with a lens stalk; the other was aphakic. The resolution available with TEM allowed detailed evaluation of cell organelles, spatial relationships, and the intra- and extracellular structural environment of the optic cup in normal and abnormal mouse embryos. Differences between the normal littermate and the trisomic optic cups, as well as between the two ts 1 structures, included the following: 1) melanin granules in the retinal layer and intraretinal space as well as in the pigment layer, 2) neither pseudostratified nor cuboidal neuroepithelium in trisomic optic cups, 3) increasing cell lysis with severity of eye defect, 4) fusion between retinal and pigment layer cells and cells from the pigment layer and head mesoderm. This investigation not only confirmed some of the abnormal morphology found in light microscopic studies of ts 1 at this gestational age but also identified other anomalies in the ts 1 eye that may play a part in the dysgenesis of this organ. The roles of larger than normal intercellular lacunae, disorganized microtubules, and the connections between different cell types in the ts 1 optic cup require further investigation.

Animals↗
PubMed1989

Changes in nuclear and nucleolar areas of endometrial glandular cells throughout the menstrual cycle.

Reproducible measures of the ultrastructural changes occurring throughout the normal human menstrual cycle are useful for defining and differentiating between normal and pathological states. Glandular endometrial functionalis epithelium obtained from five menstrual cycle subphases (early and late proliferative; and early, middle and late secretory) has been quantitated and compared for changes in nuclear and nucleolar size. These analyses indicate that (a) nuclear area significantly increases in the late secretory subphase, perhaps a requirement of endometrial regeneration; (b) nucleolar area peaks during the early secretory subphase, a necessary prelude for the later increased secretory activity; and (c) nucleolar area declines in the middle and late secretory subphases, probably due to falling hormone blood levels late in the cycle. In the proliferative phase, the majority of cells containing large nuclei and nucleoli have a relatively undeveloped cytoplasm, while the cytoplasm of those in the secretory phase contains glycogen. These cells were termed Stage 1 and 2 cells, respectively. The late secretory subphase contains some degenerating mature epithelial cells with large nuclei and small nucleoli as well as differentiated and regenerating cells with larger nucleoli. These measures establish a baseline of the normal changes in nuclear and nucleolar size as they occur throughout the normal human menstrual cycle.

Biopsy↗
PubMed1988

Ultrastructural evidence of stromal/epithelial interactions in the human endometrial cycle.

We found ultrastructural evidence of interactions between glandular epithelium and superficial stromal cells of the human endometrium during phases of the menstrual cycle. Four significant changes were observed in the transition from early proliferative (days 5 to 9) to early secretory (days 15 to 19) phases. These changes included: (1) an increase in the number and size of lamina densa disruptions, (2) an increase in the number and size of gap junctions, (3) an increase in the number and complexity of epithelial cell projections that extended through the lamina densa, and (4) an increase in close contacts between stromal and epithelial cells. The complex epithelial cell projections that extended through the lamina densa were in close proximity to stromal cells. These interactions were seen primarily in the early secretory phase. After that time (days 20 to 28) the interactions were less frequent. These morphologic results reveal complex physical interactions between epithelial and stromal cells of the adult endometrium. The interactions reach maximal development during the preimplantation phase of the endometrial cycle.

Adult↗
PubMed1988

Interaction of epithelial and stromal cells in vaginal adenosis.

Two types of direct contact between epithelial and stromal cells in patients with vaginal adenosis are documented in electron micrographs. In the first type, epithelial cells send cytoplasmic extensions through the basal lamina to achieve, at times, complete fusion with fibroblasts in the stromal compartment. In the second type, mast cells act as intermediaries between the epithelial and stromal compartments.

Epithelium↗
PubMed1985

Rat luminal cell nuclear area changes correlated with uterine growth responses induced by a low dose infusion or injection of estradiol-17 beta.

Rat uterine luminal epithelial cells (LEC) responded differently when exposed to an injection of 1.0 microgram estradiol-17 beta (E2) compared to a continuous infusion of E2 at the rate of 1.0 microgram/24 hours. After injection or beginning infusion, LEC mean nuclear area significantly decreased by 4 h, then increased thereafter. After injection, nuclear area distributions were determined at each time point. The percentage of large nuclei (greater than 40 mu 2) decreased by 4h postinjection and remained a relatively small proportion of the population, while the percentage of nuclei of 20-30 mu 2 areas increased throughout the experiment. During infusion, the percentage of large nuclei decreased by 4h after pump implantation, then increased. Only infusion induced sustained, increased uterine protein content, DNA synthesis and ornithine decarboxylase activity. This study suggests that E2 treatment modality induces differences in nuclear size in target cells as well as in biochemical parameters.

Animals↗
PubMed1984

Luteolysis induced by prostaglandin F2 alpha in the lizard, Anolis carolinensis.

The effect of exogenous prostaglandin F2 alpha (PGF) on luteal function and morphology was examined in the lizard, Anolis carolinensis. Reproductively active females were injected with 1.0 micrograms PGF, 0.1 micrograms PGF, or 0.05 ml saline. Animals were killed 2, 6, or 24 hr after injection. Prostaglandin treatment induced luteolysis as evidenced by significant decreases in plasma progesterone concentration in animals sacrificed 6 and 24 hr after treatment. Both doses of PGF were effective. However, 0.1 micrograms PGF induced luteolysis in less than 50% of the treatment group. Luteal degradation became apparent at the cellular level 24 hr after PGF treatment whereas no significant changes were observed in corpora lutea of the 2- or 6-hr postinjection specimens. These data suggest that PGF is a luteolytic agent in reptiles.

Animals↗
PubMed1984

An ultrastructural comparison of grade I and II endometrial adenocarcinoma considering estrogen and progesterone receptor status.

Eighteen (18) previously untreated patients with grade I (9) and II (9) endometrial adenocarcinoma provided endometrial samples for biochemical analysis of estrogen and progesterone receptors. The same samples were evaluated by histology and ultrastructure. Progesterone receptor negative samples (PR less than 1000 fmole/g tissue) showed more ultrastructural characteristics of malignancy and a wider range of changes than the progesterone positive specimens (PR greater than 1000 fmole/g tissue). These findings appeared to be independent of estrogen receptor status. No significant ultrastructural changes were seen when grades I and II were compared.

Adenocarcinoma↗
PubMed1984

Scanning electron microscopy of the multifilament IUD string.

Fifteen multifilament strings on Dalkon Shield IUDs removed from patients were evaluated with scanning electron microscopy. All fifteen showed deterioration of the sheath which encloses the smaller inner filaments. The greatest area of deterioration was at the attachment knot which is usually intrauterine. Deterioration of the sheath also occurs when the device is within the uterine wall or intraperitoneal. The risk of pelvic infection may be attributed to this deterioration of the sheath and contamination from that site.

Bacterial Infections↗
PubMed1969

Lipid metabolism. Evidence of a delta-oxidation pathway for saturated fatty acids.

1. Specific radioactivities of milk triglyceride fatty acids and gamma- and delta-hydroxy fatty acids were measured after the intramammary infusion of [1-(14)C]acetate, delta-hydroxy[1-(14)C]laurate and [1-(14)C]laurate as their sodium salts into fed lactating goats. 2. Net incorporations of the radioactive tracer into the total milk lipids were comparable, being 16, 17 and 21% of the label infused respectively. 3. The specific radioactivities of the C(4)-C(8) fatty acids after [1-(14)C]acetate infusion were lower than those of the C(10)-C(14) fatty acids. 4. After delta-hydroxy[1-(14)C]laurate administration the milk triglyceride fatty acids were labelled and their specific radioactivities were characterized by decreasing values with increasing chain length of the fatty acids, implicating C(4) unit incorporation. 5. The gamma- and delta-hydroxy fatty acids isolated after [1-(14)C]laurate infusion were highly labelled and the milk triglyceride fatty acids, other than laurate, exhibited a labelling pattern similar to that of the fatty acids derived from the radioactive delta-hydroxy fatty acid. 6. Evidence is presented for the existence of saturated fatty acid delta-oxidation in the mammary gland, in which the gamma- and delta-hydroxy fatty acids are active intermediates.

Acetates↗
PubMedDate not supplied

Lipid phase separation correlates with activation in platelets during chilling.

When human platelets are chilled below 22 degrees C, they spontaneously activate, a phenomenon that severely limits their storage life. It has previously been proposed that there is a correlation between cold-induced platelet activation and passage of the membranes through a liquid-crystalline to gel phase transition. Because animal models are essential for developing methods for cold storage of platelets, it is necessary to investigate such a correlation in animal platelets. In this work, horse platelets were used as a model, and it was found that cold-induced morphological activation is related to the lipid phase transition. Using fluorescence microscopy with the lipophilic fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (Dil-C18), and Fourier transform infrared spectroscopy (FTIR), it was found that lipid phase separation occurs during cooling and low temperature storage. Furthermore, removal of cholesterol from the plasma membrane also induced a phase separation, possibly between specific phospholipid classes. Steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium-DPH (TMA-DPH) were compared in cells and multilamellar vesicles (MLV) composed of platelet lipids. Cholesterol depletion led to a decrease in the fluorescence anisotropy of the two probes, which can be explained by changes in the order of the phospholipid molecules. In addition, the lipid composition and fatty acid profile of the cellular phospholipids were determined. Based of the similarities between horse and human platelets, it is suggested that horse platelets may be used as a model for studying cold-stored platelets. The results are discussed in relation to the possible role of phase separation during cell signalling.

Animals↗
PubMedDate not supplied

Physical properties of membrane fractions isolated from human platelets: implications for chilling induced platelet activation.

In previous studies, it has been suggested that chilling induced activation of human platelets is related to a lipid phase transition seen in membrane lipids. Those studies showed a single, surprisingly cooperative transition in human platelets, as determined by Fourier transform infrared (FTIR) spectroscopy, findings that are confirmed here with calorimetric measurements. Such transitions have now been studied in membrane fractions obtained from the platelets and it is reported that all fractions and purified phospholipids show similar transitions. In order to obtain these data it was necessary to develop means for separating these fractions. Therefore, a novel method for isolation and separation of dense tubular system (DTS) and plasma membranes in human platelets is described here. Lipid analysis showed that phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were the dominant phospholipids in both fractions, whereas cholesterol and sphingomyelin (SM) were predominantly located in the plasma membranes. Thermotropic phase transitions in the two membrane fractions, determined by differential scanning calorimetry (DSC) and FTIR spectroscopy were found to occur at about 15 degrees C, similar to the Tm of intact human platelets. These data are discussed in relation to the role of the DTS and plasma membranes in the cold-induced activation of human platelets.

Blood Platelets↗
PubMedDate not supplied

Induction of lung lesions in female rats following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8,-Tetrachlorodibenzo-p-dioxin (TCDD) has been classified as a known human carcinogen, and epidemiologic studies identify the lung as one of the target organs. Few experimental studies have attempted to characterize pulmonary effects of TCDD exposure. In this study, we characterize the induction of lesions in the lung by chronic oral TCDD exposure in diethylnitrosamine (DEN)-initiated or noninitiated female Sprague-Dawley rats. Two or 18 weeks after initiation, rats were treated with TCDD continuously for 14, 30, or 60 weeks by biweekly oral gavage (1,750 ng TCDD/kg) at a dose equivalent to 125 ng/kg body weight per day (controls received corn oil). To assess the time dependence and reversibility of potential changes, some groups included withdrawal periods of 16 or 30 weeks after 30 weeks of TCDD treatment. TCDD treatment alone for 60 weeks caused significant increases in alveolar-bronchiolar (AB) metaplasia. TCDD treatment of DEN-initiated animals for 60 weeks resulted in a significant increase in bronchiolar epithelial hyperplasia. These increases were not observed in animals treated with TCDD for 30 weeks followed by corn oil for 30 weeks, indicating that the development of these lesions required continuous exposure to TCDD. AB hyperplasia increased in an age-dependent manner after DEN initiation but was unaffected by TCDD treatment. Expression of the aromatic hydrocarbon receptor (AHR) and induction of CYP1A1 was observed only in bronchiolar Clara and ciliated cells, indicating that the mechanism of induction of AB metaplasia may be mediated by the AHR. TCDD elimination half-life was monophasic in the lung, and serum and was estimated to be 39.7 days and 44.6 days, respectively, independent of age, tissue TCDD concentration, or body weight. This is the first report to identify the AB region as a target for TCDD-induced metaplastic and proliferative changes after chronic oral exposure.

Adenoma↗