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J Leighton

Publications and source records attributed to J Leighton.

At least 37 records · Page 2Linked to original sources
PubMed1991

Radial histophysiologic gradient culture chamber: rationale and preparation.

Histophysiologic gradient culture methods reconstitute important spatial relationships that occur in nature between a parenchyma and its supporting stroma. At the epithelial-stromal interface, epithelia are firmly attached to the stromal substrate, initiation of renewal takes place, and metabolites are exchanged by a process of diffusion between epithelium and substrate. Other spatial imperatives characteristic of stratified epithelium are high density of cells, gradients of maturation, and continuity of epithelia along the entire course of the stromal-parenchymal interface. In radial gradient culture these relationships of epithelial cells, and supporting substrates are reconstituted. The culture chamber consists of a thin-walled cylinder, 2 to 3 mm in diameter and 3 cm long. The wall is a transparent collagen membrane in whose substance is embedded a reinforcing nylon mesh. To prepare a culture, one end of the cylinder is ligated, 1 or 2 particulate inocula are inserted in the open end of the cylinder, guided toward the ligature, and the open end is ligated. Subsequently, during incubation in a container with medium, the explants attach and proliferate. Proliferation and migration result in the cylinder being completely lined by a complex organoid tissue with structural characteristics of the original tissue. The tissue patterns in radial gradient culture of two human cell lines, RT-4, a bladder cancer, and 87 x 50, an ovarian cancer, are illustrated.

Cell Line↗
PubMed1990

Transforming growth factor beta 2 differentially modulates interleukin-1 beta- and tumour-necrosis-factor-alpha-stimulated phospholipase A2 and prostaglandin E2 synthesis in rat renal mesangial cells.

Treatment of rat glomerular mesangial cells with transforming growth factor beta 2 (TGF beta 2) stimulates prostaglandin E2 (PGE2) synthesis. Actinomycin D, cycloheximide and diclofenac attenuate the TGF beta 2-induced PGE2 formation. As shown previously, two proinflammatory cytokines, interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha), are potent stimuli for PGE2 and phospholipase A2 secretion from mesangial cells. We report here that, whereas TGF beta 2 potentiates the IL-1 beta- and TNF alpha-evoked PGE2 production, it strongly inhibits the phospholipase A2 secretion induced by both cytokines. In addition, the inhibitory effect of TGF beta 2 on phospholipase A2 secretion is not due to the augmented PGE2 formation.

Animals↗
PubMed1989

Reconstitution of the malignant phenotype of genitourinary cancer in gradient culture.

The diagnosis of cancer is made on histologic examination by recognizing the characteristics of the malignant phenotype, i.e. abnormal cells in abnormal groupings, often in abnormal locations. Histophysiologic gradient culture reconstitutes conditions that meet the spatial imperatives of tissues in nature. A variety of carcinomas arise in the genitourinary system involving both glandular and stratified epithelium. To be considered here are the contrasting polarizations of proliferation of normal and neoplastic rat urothelium, the continuity of sheets of epithelium in nature, the poorly understood stable and unstable interepithelial boundaries, and the formation of organoid endocrinelike tissue in histophysiologic gradient culture of normal human amnion epithelium.

Adenocarcinoma↗
PubMed1988

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. II. Review of past studies of WIC.

We reviewed past work relating WIC benefits to birth weight, perinatal and infant survival, anemia, child growth, and dietary intake. Despite many uncertainties, the probable range of reduction in the rate of low birth weight was approximately 1-2% and the increase in mean birth weight ranged from 0 to approximately 60 g. There was too little information to securely estimate effects of WIC on perinatal and infant mortality nor on the dietary intake of women or children. Although the number of studies was small, there probably were important effects of WIC on rates of childhood anemia. There is too little evidence to come to any conclusion on effects during pregnancy. There is little evidence that the WIC program has affected children's linear growth.

Birth Weight↗
PubMed1988

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. IV. Study methodology and sample characteristics in the longitudinal study of pregnant women, the study of children, and the food expenditures study.

The longitudinal study of pregnant women enrolled a national probability sample of 5,205 women first certified for WIC and 1,358 comparable low-income pregnant women in 174 WIC clinics located in 58 areas in the contiguous 48 states and in 55 prenatal clinics without WIC programs in counties with low program coverage. The women completed 24-h dietary recalls, histories of food expenditures, health care utilization, health and sociodemographic status, and anthropometric assessment. At late-pregnancy follow-up 3,967 WIC and 1043 control women were interviewed and 853 WIC and 762 control women completed 1-wk food expenditure diaries. Birth outcome was abstracted (from hospital records) for 3,863 WIC and 1058 control women. Anthropometry, dietary intake, health, and use of health services were related to WIC among 2,619 random low-income preschoolers. Psychological development was assessed in 526 children aged 4 and 5 y. Control women had higher income, education, and employment status; therefore, WIC program benefits probably were underestimated.

Child Nutritional Physiological Phenomena↗
PubMed1988

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. V. Longitudinal study of pregnant women.

The major associations with the Special Supplemental Food Program for Women, Infants, and Children (WIC) in pregnancy were increased intake of protein, iron, calcium, and vitamin C (four of five targeted nutrients) and of energy, magnesium, phosphorus, thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12; reversal of low weight gain in early pregnancy; smaller fat stores in late pregnancy; reduced frequency of premature rupture of the uterine membranes; larger infant head circumference with no effect on birth weight and length; increased birth weight and head circumference with better program quality; and lower fetal mortality of appreciable but not significant magnitude. Incremental energy intake was comparable to that in most small-scale supplementation trials. There was no evidence of effects on frequency of prenatal care, use of alcohol or tobacco, the intention to breast-feed, or the rate of breast-feeding. Maternal alcohol intake was associated with depressed infant head circumference, over and above effects on birth weight and length.

Anthropometry↗
PubMed1988

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. VI. Study of infants and children.

The major associations with the Special Supplemental Food Program for Women, Infants, and Children (WIC) in preschool children were better dietary intake associated with current WIC participation, especially for Fe, vitamin A, and vitamin C, but there were no increases in energy intake and, after infancy, no residual benefits from past WIC participation; strongest dietary effects among children who were poor, black, or in single-parent or large families (children lost to WIC were as needy as those currently enrolled); shorter stature, suggesting effective targeting (with enrollment in utero there was no parallel deficit in head circumference, which is consistent with results for newborns); better immunization and more frequent regular source of health care but no more frequent use of preventive health services; and better vocabulary with WIC participation begun in utero; better digit memory with entry into the program after the first birthday (differences that emerged only after statistical adjustment for sociodemographic factors); and more advantageous child behavior (NS).

Body Height↗
PubMed1988

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. I. Background and introduction.

The Special Supplemental Food Program for Women, Infants, and Children (WIC) aims to improve the nutrition and health of low-income, nutritionally at-risk pregnant women and preschool children with supplemental food, nutrition education, and coordination of health care. Started in 1972, it recently served greater than 3.4 million persons monthly and at a cost of $1.66 billion annually. The National WIC Evaluation (NWE) consisted of four studies: The historical study estimated changes in birth outcome attributable to WIC from 1972 to 1980 in 19 states and the District of Columbia from WIC program data and vital statistics. The longitudinal study of pregnant women compared dietary intake, weight gain, anthropometry, duration of gestation, birth weight, and infant length and head circumference between a representative national sample of WIC participants and economically comparable women. The cross-sectional study of preschool children related WIC to dietary intake, anthropometry, and psychological development. The food expenditures study estimated the impact of WIC on family grocery and other food expenditures.

Child Welfare↗
PubMed1986

Evaluation of an enkephalin analog in men with castor oil-induced diarrhea.

This study was a parallel, double-blind, placebo-controlled evaluation of acute doses of nifalatide, an enkephalin analog, in subjects with castor oil-induced diarrhea. Seventy-two subjects completed the study. The time to first stool after castor oil administration was significantly greater after the 16 and 48 mg doses of nifalatide as compared with placebo dosing. The same doses of nifalatide also decreased the overall stool frequency, the frequency of abdominal cramping, and the incidence of nausea and vomiting. There were no clinically significant, drug-related changes in the physical examination results, ECG, vital signs, or clinical laboratory parameters. The only increased adverse experiences that appeared to be related to the drug were dizziness and mild dry mouth.

Administration, Oral↗
PubMed1985

Radial gradient culture on the inner surface of collagen tubes: organoid growth of normal rat bladder and rat bladder cancer cell line NBT-II.

Radial histophysiologic gradient culture uses thin walled, permeable collagen tubes to house inocula in the form of either tissue explants, aggregates of cells, or dissociated cells. The outgrowth from these inocula spreads on the inner surface of the cylindrical tube, completely lining the lumen. Metabolites are exchanged through the wall of the collagen tube by diffusion from the pool of medium surrounding the cylinder. Urothelial cells form organoid stratified epithelium. A histophysiologic gradient occurs with the basal surface of the epithelium attached to the collagen wall. At this interface, for normal bladder, the initiation of epithelial renewal is seen in the basal zone, as shown by incorporation of tritiated thymidine. The simulation of conditions in nature is attained by the exchange of metabolites between the pool of medium and the basal zone of the epithelium. NBT-II appears as two concentric stratified epithelia. Isotopic labelling is seen throughout the epithelium attached to the collagen membrane. In the superficial stratified epithelium remnants of nuclei are seen without isotopic labelling. Preparation of living cultures and, after fixation, of histologic sections is technically easy.

Animals↗
PubMed1985

The chick embryo in toxicology: an alternative to the rabbit eye.

The chorioallantoic membrane (CAM) of the chick embryo is readily accessible for experimentation. It is a complete tissue that responds to injury with classical inflammatory reactions. It is limited to the late phase of embryologic life, and is without the sense of pain. Focal topical application of various household products onto the CAM results in local injury and reactions that differ in severity from one product to another. For any single product, tested as a sequence of dilutions on a series of membranes, the CAM responds with decreasing intensity that parallels the decreasing dosage. The membrane is prepared for study according to the method of Zwilling (Transplantn Bull 1959, 6, 115). The test material is applied in a Teflon ring to the 14-day-old CAM, to localize the application site. The macroscopic response is scored on day 17 of incubation. The results of analysis of histological preparations are found to correlate with macroscopic appearance. When a series of preparations was ranked according to the severity of the response each induced on the CAM, there was a good correlation with the ranking of the same preparations in the Draize test.

Allantois↗
PubMed1985

Characterized full-length and truncated plasmid clones of the crystal protein of Bacillus thuringiensis subsp. kurstaki HD-73 and their toxicity to Manduca sexta.

Bacillus thuringiensis subsp. kurstaki HD-73 produces a crystal protein which is lethal to many lepidopteran larvae. The gene encoding this crystal protein has been isolated from a 75-kb plasmid and engineered into a recombinant Escherichia coli plasmid for analysis. The complete nucleotide sequences of the coding region and 387-bp 5' and 376-bp 3' to the coding region have been determined. The 3537-bp of the coding region specify a protein of Mr 133 330. The full-length gene and several 3' -truncated derivatives of the gene were examined in both E. coli and in an E. coli minicell-expression system to determine if the carboxy end of the protein is essential for toxicity. The results presented here provide the primary structure of the crystal protein gene and show that the N-terminal 68-kDal peptide is toxic, but at a lower level than the full-length gene product.

Amino Acid Sequence↗
PubMed1984

The propagation of cancer, a process of tissue remodeling. Studies in histophysiologic gradient culture.

Effective study of the malignant phenotype at the tissue level requires model systems that are intelligible both to cell biologists and to pathologists, and that also observe the spatial imperatives intrinsic to tissues in nature. Malignant cells commonly appear in multicellular units, and growth of tumor tissue is seen as an increase in the number of cells and multicellular units. The supporting stroma frequently has an abnormal appearance, and this component of the tissue also increases in mass as the tumor enlarges and spreads. The direction of invasion is influenced by the direction of available metabolites. Histophysiologic gradient culture complies with nature's spatial rationale, since at the substrate-parenchymal interface three functions coincide. These are anchorage, initiation of epithelial renewal, and complete exchange of metabolites. Our model system provides a setting for reconstructing and manipulating many features of the malignant phenotype seen in cancer tissues in nature, such as abnormalities in the sequence of maturation of stratified epithelium, hyperplasias, dysplasias, interaction between different types of epithelium, aggregate formation, tumor angiogenesis, and neoplastic blockade.

Animals↗
PubMed1984

Organoid structure of normal rat bladder in unilaminar and bilaminar histophysiologic gradient culture : methods and observations.

In lining epithelium of mammals certain recurrent architectural patterns are recognized that may be critical for epithelial organization in culture. Among these structural imperatives are three dimensional growth, restricted migration of cells, histophysiologic gradients, and continuity of epithelial membranes. Histophysiologic gradient culture procedures have been developed to comply with requirements suggested by normal tissue architecture. In a small chamber, 5 mm diam, epithelium grows attached to a thin permeable transparent collagen membrane or sandwiched between two apposed collagen membranes. The chamber is held in a plastic capsule so that metabolic exchange is limited to substances that diffuse across the collagen membranes to the adherent basal layer of epithelium. On a single membrane after 2 wk of growth, normal urothelium appears as a diffusely hypercellular urothelium, 6 to 10 cells thick. As the culture period is extended by 2 or more wk, multiple nodules of urothelium extend from the basal surface into the subepithelial space between the epithelium and the collagen membrane. Normal bladder, cultured between two apposed collagen membranes, gives rise in a few days to confluent epithelium that contains many extracellular cysts. Through an apparent merging of cysts, after 2 wk the urothelium appears as a highly organoid structure, a flattened cyst lined by completely stratified polarized urothelium. Such microbladders consist of a stratified epithelium without interruption of continuity. With histophysiologic gradient culture, processes in carcinoma and precursor lesions are accessible to study at the level of tissue organization.

Animals↗
PubMed1984

Comparison of invasiveness and non-invasiveness of two epithelial cell lines in vitro.

Two epithelial cell lines of urological origin have been compared for their invasiveness in an in vitro three-dimensional culture system, using embryonic chick cardiac muscle as host tissue. Cells from the Nara bladder tumor line (NBT-II), an invasive tumor in the rat, invaded and progressively occupied the cardiac muscle which degenerated. Cells from a dog kidney line (MDCK), which are of low tumorigenicity in nude mice, failed to invade into the cardiac muscle in vitro. MDCK cells formed a structurally polarized epithelium around the heart tissue. MDCK is the first established epithelial cell line that has been found to grow in this invasion assay culture system and yet did not invade the heart fragment.

Animals↗
PubMed1984

Anatomy of the chick chorioallantoic membrane relevant to its use as a substrate in bioassay systems.

Scanning electron microscopy was used in this investigation to characterize and contrast the chorionic surface of 11 day chick chorioallantoic membranes (CAM) prepared by either the classical dropping technique or the Zwilling technique. The structure of the chorionic blood sinus and its relationship to the chorionic ectoderm were also examined. The Zwilling CAM has been proposed as the substrate in an assay being developed by investigators in this laboratory, an assay which is intended as an alternative to the Draize Rabbit Eye Irritancy Test. The purpose of this study was to define the substrate. The results show considerable uniformity of the Zwilling CAM surface in comparison to the dropped CAM. Broad areas of exposed basement membrane were an unexpected finding on the surface of the dropped CAM. It appears that this basement membrane is made up of more than just the thin discontinuous basal lamina seen with the transmission electron microscope. The findings of this study are pertinent to chick embryo physiology as well as to toxicologic assays and tumor cell assays which utilize the CAM.

Allantois↗