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W H Utian

Publications and source records attributed to W H Utian.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of estrogen in vivo on coronary vascular resistance in perfused rabbit hearts.

Estrogen or its vehicle was given daily to three groups of ovariectomized rabbits for various lengths of time, after which coronary flow was measured in their isolated perfused hearts. In one group, intramuscular injections of estrogen (40 micrograms/kg) for 7 or 14 days increased coronary flow by 40-50% (P < 0.05). In rabbits given estrogen intramuscularly for 7 days, the coronary flow returned to the basal level within 7 days after the estrogen injections were discontinued. In a second group of animals, intravenous injections of estrogen (10 micrograms/kg) for 4 days increased the coronary flow by 45% (P < 0.01). In a third group, we administered the estrogen transdermally for 4 days, and we measured the plasma estrogen levels at the end of this period. The coronary flow in this group was increased by 52% (P < 0.001), and the plasma estrogen levels ranged from 39 to 800 pg/ml. In all groups of experiments, the increments in coronary flow evoked by estrogen were virtually abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase. We conclude that estrogen regulates coronary blood flow, in part by upregulating nitric oxide synthase in the coronary vasculature.

Administration, Cutaneous↗
PubMed1995

Distribution of unesterified cholesterol-containing particles in human atherosclerotic lesions.

The objective of the study was to characterize unesterified cholesterol particles in human aorta and to correlate the findings with the severity of aortic atherosclerosis. Human tissues were processed under conditions that preserve deposits of unesterified cholesterol agglomerates. Filipinfluorescence was determined by using a novel triple band pass filter. The pattern of unesterified cholesterol deposits was age related and correlated with the severity of atherosclerosis. We found three types of deposits: 1), small spherulites (3 to 5 mu), which were depicted in both the media and intima in individuals as early as age 16, and which, in more advanced ages, showed an increase in density and a tendency to aggregate extracellularly throughout the intima in clusters; 2), elongated structures (10 to 30 mu in the middle zone of the intima), the density of which was directly related to the severity of atherosclerosis; and 3), large (100 mu), irregular deposits found mainly in the core of atherosclerotic plaques. The medium size deposits, compared with those found in the core of atherosclerotic plaques, retain their overall size (10 to 30 mu), uniformity (oval elongated), and localization (middle zone of the intima). On the basis of these observations we hypothesize cholesterol deposition in two stages of aggregation: 1), early degradation of infiltrating low density lipoprotein particles forming unesterified cholesterol-rich vesicles in the vessel wall, followed by aggregation to spherulites in the lower part of the intima; and 2), more massive agglomeration of particles containing unesterified cholesterol and calcium phosphate in the midzone of the intima. Because in the second stage of aggregation the transition of cholesterol to the solid state has already occurred, it is irreversible.

Adolescent↗
PubMed1994

Human uterine cervical epithelial cells grown on permeable support--a new model for the study of differentiation.

The purpose of the present study was to establish culture conditions for human uterine cervical epithelial cells on permeable support and to determine how it affects cervical cell differentiation. Human ectocervical epithelial cells (hECE), HPV-16 immortalized hECE cells (ECE16-1) and Caski cells were grown on collagen-coated filters. Culture conditions, density of cells in culture and expression of epithelial and cervical-cell phenotypic markers were determined and compared in cells grown on filter and on solid support. Compared with the latter, cultures on filter had a higher cell density, hECE cells stratified to 5-12 cell layers compared to 1-3 on solid support, and cells of all three types expressed intercellular tight junctions. The cytokeratin profiles revealed differences between the three cell types as well as differences within the same cell species when grown on filter, compared to solid support. Of particular importance was the finding of a higher expression of K-13 in hECE grown on filter compared to solid support; K-13 is a marker of ectocervical cell differentiation. The cytokeratin profiles of the cultured hECE, ECE16-1 and Caski cells resembled those of ectocervical, squamous metaplastic and endocervical epithelia, respectively. hECE and ECE16-1 expressed involucrin protein, the level of which in both was higher in cells grown on filter compared to solid support. Polarization of the cultures was determined by morphology (stratification of hECE cells, expression of pseudomicrovilli in the apical cell membrane), selective apical vs. basolateral secretion of [35S]methionine- and [35S]cysteine-, [3H]fucose- and [14C]glucosamine-labeled molecules, and positive short-circuit current (Isc) under voltage-clamp conditions. Confluency of the cultures was determined by measuring transepithelial unidirectional fluxes of inert molecules with different molecular weights (MWs) through the paracellular pathway, and by measuring transepithelial conductance. The results indicated transepithelial permeability of 7-22.10(-6) cm.sec-1, which was 5-100 fold smaller compared to blank inserts, with a cut-off MW of 40-70 kDa for hECE and Caski cells. Transepithelial conductance ranged 18.5 to 51.5 mS.cm-2, indicating a leaky but confluent epithelia. Collectively the results indicate the epithelial nature of the cells and their improved differentiation when grown on filter support; hECE is a model for ectocervical epithelium while ECE16-1 and Caski express phenotypic characteristics of squamous metaplastic cervical epithelium and endocervical epithelium respectively.

Carcinoma, Squamous Cell↗
PubMed1994

ATP decreases acutely and reversibly transport through the paracellular pathway in human cervical cells.

We studied the effect of ATP on transepithelial transport through the paracellular pathway in human cervical cells. Transepithelial conductance and transepithelial permeability (determined from the measurements of unidirectional flux of inert molecules) were measured in Caski cells grown on permeable support. Transepithelial conductance was 55.9 +/- 17.7 mS/cm2 and permeability was 12.5 +/- 2.7 x 10(-6) cm/s for a 0.51-kDa probe. Addition of ATP to the medium decreased acutely and reversibly the conductance and the permeability to probes between 0.18 and 10 kDa by 23-31% in a dose-related fashion; the 50% effective concentration was 1 microM, with a maximal effect at 5-10 microM extracellular ATP. The ATP effect was observed regardless of the pressure gradient across the epithelium. These results indicate that extracellular ATP in micromolar concentrations decreases acutely and reversibly the permeability through the paracellular pathway in cervical cells, possibly by affecting the permeability of the tight junctions and the resistance of the intercellular space. On the basis of these data, we speculate that ATP may play a role in the regulation of solutes and fluid transport across the cervical epithelium in vivo.

Adenosine Triphosphate↗
PubMed1993

A risk-benefit appraisal of transdermal estradiol therapy.

Estrogen replacement therapy (ERT) is very effective in relieving many menopausal symptoms such as hot flushes, night sweats, urogenital atrophy and psychological disturbances. Moreover, it is effective in the prevention of postmenopausal osteoporosis and has a favourable effect on some risk factors for cardiovascular disease in the long term, via several mechanisms including mediating effects on the lipid profile. Most of these beneficial effects are maintained with transdermal estradiol therapy, involving the use of a cutaneous delivery system attached to the skin which delivers a controlled rate of estradiol over a period of up to 4 days. However, the clear demonstration of a favourable effect on some risk factors for cardiovascular disease remains to be established. Transdermal administration of estradiol appears to be at least as effective as oral conjugated estrogen therapy on most of the end-points which have been evaluated, but allows a lower dose to be used, avoiding some of the metabolic adverse effects experienced with oral treatment. Endocrinological adverse effects, such as breast tenderness, breakthrough bleeding and fluid retention, are similar in both treatments, and can be minimised by dose adjustments in most cases. The most common adverse effects related to transdermal therapy are local skin reactions at the site of application. These are usually mild and transient in nature, and can be overcome by changing the site of application. Serious risks of transdermal therapy appear to be the same as those for other forms of ERT, namely an increased risk of endometrial hyperplasia and cancer with estrogen therapy alone. However, combination therapy involving the sequential administration of a progestogen has been shown to substantially reduce the risk of endometrial proliferation. The potential increased risk of breast cancer has been controversial and appears to be minimal with ERT. The role of progestogens on breast cancer risk remains controversial, but the data to date do not indicate any significant change in risk when progestogens are added to ERT.

Administration, Cutaneous↗
PubMed1991

Sex steroids and growth factors differentially regulate the growth and differentiation of cultured human endometrial stromal cells.

We have studied the interaction between growth factors and sex steroids in regulating human endometrial stromal cell growth and differentiation using an in vitro serum-free cell culture model system. None of the growth factors [epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin, insulin-like growth factor-I (IGF-I), IGF-II, or platelet-derived growth factor] stimulated the growth of human endometrial stromal cells grown in progestin-free medium. However, the growth of progestin-treated cultures was dramatically increased by EGF, bFGF, or platelet-derived growth factor, but not by insulin, IGF-I, or IGF-II. Estrogen could not substitute for progesterone in this protocol, and coadministration of estrogen with progestin did not enhance the response over that to progesterone alone. In contrast to their positive effects on growth, only EGF, not bFGF, stimulated stromal cell differentiation, as measured by an increase in PRL, laminin, and fibronectin production; moreover, stimulation of differentiation was dependent upon the presence of progestin in the culture medium. Thus, human endometrial stromal cell growth is 1) regulated by a discrete set of growth factors, only a subset of which regulates stromal cell differentiation; and 2) regulation of stromal cell growth and stromal cell differentiation by growth factors is progestin dependent. Our results provide direct evidence for interaction between growth factors and sex steroids in the regulation of stromal cell growth and differentiation in vitro and suggest that growth factors may be absolutely required in conjunction with progesterone for the decidual response in vivo.

Cell Differentiation↗
PubMed1990

Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues.

The human uterus repeatedly exhibits cyclic biochemical and cytological changes during the reproductive period of life. These changes are the result of a well-characterized endocrine network involving the hypothalamus, pituitary, and ovary. The exact nature of the mechanism(s) by which the sex steroids act on the uterus remains to be elucidated. Possible local mediators of hormonal action on the uterus include polypeptide growth factors. Using the method of RNA transfer blot hybridization, we have analyzed tissue samples from the cycling human endometrium and tissue samples of human myometrium and myometrial benign tumor (leiomyoma) for the presence of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) RNA. All the uterine tissues examined possessed RNA for PDGF-B chain and IGF-I and -II. Two transcripts were observed for PDGF-B chain, four were observed for IGF-I, and eight were observed for IGF-II. Overall, the relative abundance of PDGF-B chain RNA was consistent in all of the uterine tissues examined. In contrast, IGF RNA relative abundance varied. IGF-I RNA was highest in late proliferative stage endometrium, and IGF-II RNA was highest in early proliferative stage endometrium. Both IGF-I and IGF-II RNAs were greater in amount of leiomyoma than in myometrium. The increased IGF-I RNA in late proliferative-stage human endometrium correlates with the known elevation of estradiol secretion by the ovary and the increased concentration of uterine estradiol receptors during this stage of the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrium↗
PubMed1990

The menopause in perspective. From potions to patches.

This article attempts to survey our current understanding of the human female climacteric and the role of hormone replacement in its treatment. As a potential endocrinopathy, the climacteric deserves appropriate diagnostic recognition and selective preventive pharmacotherapy. The impact of sometimes conflicting influences such as nutritional, dietary or lifestyle changes, exercise, smoking, drugs, alcohol and other medications, all need differentiation from true hormonal responses. The climacteric, one syndrome occurring over a period of time, has potentially lethal effects, notably coronary heart disease and complications of osteoporotic fractures. However, therapy itself carries major problems, the cancer question being the most important. The dilemma of risk-benefit planning is reviewed and likely future developments are outlined. The role of the new North American Menopause Society is explained.

Endocrine System Diseases↗
PubMed1990

Maintenance of in vivo-like keratin expression, sex steroid responsiveness, and estrogen receptor expression in cultured human ectocervical epithelial cells.

In the present manuscript we demonstrate that ectocervical epithelial cells (ECE cells) retain a high degree of differentiated function when cultured using feeder layers. We characterize the cultured cells with respect to morphology, expression of cytokeratins, responsiveness to sex steroids, and the presence of estrogen-binding sites. Like ectocervical cells in vivo, the cultured cells display a typical epithelial cell morphology and undergo extensive stratification and envelope (superficial cell) formation. Like the in vivo ectocervical epithelium, the cultured ECE cells express type I cytokeratins K13, K14, K16, K17, and K19 and type II cytokeratins K5 and K6. Under normal culture conditions, however, cytokeratins K1, K2, K4, K11, and K15, which are expressed in vivo, are not expressed. An interesting finding is that ECE cells, in contrast to endocervix and epidermis in vivo and cultured epidermal keratinocytes, express very abundant levels of K13. In fact, K13 appears to be a specific marker of ECE cells in the female reproductive tract. When incubated with 10 nM diethylstilbestrol, ECE cell envelope production increased 3-fold, while incubation with 100 nM progesterone decreased envelope formation 3.4-fold. Simultaneous incubation with progesterone antagonized the diethylstilbestrol stimulation. Thus, in vivo-like sex steroid regulation of ECE cell differentiation is maintained in culture. In addition, the cells possess a high affinity, limited capacity binding site for estradiol that has a Kd of 1.2 +/- 0.1 nM. This system is likely to provide a useful model for the study of sex steroid regulation of normal ectocervical epithelial cell function.

Cells, Cultured↗
PubMed1990

Myometrial oxytocin receptors levels in the pregnant rat are higher in distal than in proximal portions of the horn and correlate with disparate oxytocin responsive myometrial contractility in these segments.

Distal (D) segments of the pregnant rat uterine horn express myometrial oxytocin receptors (MORs) earlier than proximal (P) segments (day 18 vs. 20, respectively); the levels in D segments remain higher than in P segments throughout days 21-22 and correlate with the segment-specific myometrial sensitivity to oxytocin. While progesterone (P4) had no effect on MOR levels, RU486 increased (t1/2 6-12 h) MOR levels both in D and P segments, particularly in days 12-17, and the levels in the P segment equaled those in the D segment. Estradiol had no effect on MOR levels in days 20-22; in days 16-19 estradiol increased MOR levels particularly in the P segment, and the levels in the latter were higher than in the D segment. Capillary plasma P4 levels were higher in P vs. in D myometrial segments. These results indicate, in the pregnant rat, a local uterine control of D greater than P MOR expression by P4 withdrawal beginning in day 18. We hypothesize that the D greater than P MOR expression determines a role for oxytocin in initiating myometrial contractions in the D segment, while in active labor another class of agent(s) assume that function in more proximal segments.

Animals↗
PubMed1990

Cultured human ectocervical epithelial cell differentiation is regulated by the combined direct actions of sex steroids, glucocorticoids, and retinoids.

During the menstrual cycle, the ectocervical epithelium undergoes a cyclic change in differentiation that is correlated with changes in the circulating levels of estrogens and progestins. To better understand the mechanisms underlying this regulation, we have developed an ectocervical epithelial cell (ECE cell) culture system that responds in a physiological manner to stimulation by estrogens and progestins. We have recently proposed that four classes of hormones (retinoids, estrogens, progestins, and glucocorticoids) may play an important role in regulating differentiation. In the present paper we test this hypothesis directly by making detailed dose-response curves. Our results demonstrate that estrogen increases ECE cell differentiation, as measured by release of cornified envelopes (superficial cells), while progesterone decreases envelope production. The effects are dose dependent and within the expected physiological range (0.01-10 nM estrogen; 0.1-100 nM progesterone). Very low concentrations of Ro 13-6298 (0.01-10 nM), a synthetic retinoid, decreased envelope production, while hydrocortisone (0.1-50 nM) increased envelope production and cell growth. Importantly, agents that enhance envelope production are neutralized by agents that reduce envelope formation and vice versa. Based on these findings we conclude 1) that the differentiation-enhancing actions of glucocorticoids and estrogens can be antagonized by either progestins or retinoids, and 2) that glucocorticoids and retinoids are likely to determine the ECE cell differentiation set-point in vivo, with the sex steroids directly modulating the phenotype of the ECE cells around this set-point during the menstrual cycle. Moreover, these results appear to explain some of the clinical descriptions of changes in ectocervical cell morphology resulting from hyper- and hypoestrogenic stimulation.

Benzoates↗
PubMed1989

In vitro fertilization (IVF)-surrogacy: application of IVF to women without functional uteri.

Women with absent or dysfunctional uteri consented to controlled ovarian stimulation, ovum aspiration, in vitro fertilization, and embryo culture. Cleaving preembryos were transferred to recipient (surrogate) women whose menstrual cycles were in approximate synchrony with the ovum donor. None of the embryo recipients received medication. Six cases are described, resulting in one spontaneous loss at 6 weeks, four full-term deliveries, and one ongoing pregnancy. HLA typing demonstrated all babies to be genotypic offspring of the gamete donors.

Female↗