Biomedical subjects

J Yeh

Publications and source records attributed to J Yeh.

At least 55 records · Page 3Linked to original sources

PubMed1996

Association between cervical neoplasia and apoptosis as detected by in situ nuclear labeling.

Invasive cervical cancer is thought to arise from the progression of precancerous lesions. How these lesions proceed from precancers to cancer remains unknown. Data regarding other tissues indicate that altered programmed cell death (apoptosis), in addition to cellular proliferation, is associated with the development of neoplasia. Therefore, in order to better understand the development of cervical neoplasia, we investigated the rate of apoptosis in cervical precancer and cancer. Archival cervical samples from normal epithelium (n = 11), low-grade squamous intraepithelial lesions (LSIL, n = 11), high-grade squamous intraepithelial lesions (HSIL, n = 10), and squamous cancers (n = 10) were evaluated for chromatin cleavage, a hallmark of programmed cell death. We used in situ end-labeling of DNA strand breaks by terminal deoxynucleotidyltransferase incorporation of biotinylated deoxyuridine to 3'-OH ends of DNA, identified by a nickel-avidin-peroxidase. The apoptotic index (sum of apoptotic bodies divided by the total nuclei times 100) significantly decreased (P < 0.001) as the degree of neoplasia increased: 3.5% (+/-0.4) in normal cervical epithelium (4.8 +/- 0.4) in LSIL, 1.4% (+/-0.4) in HSIL, and 0.4% (+/-0.1) in squamous cancers. Compared to normal epithelium, the total cell number per 10 mm2 increased significantly (P < 0.001): 124 (+/-12) in normal epithelium, 162 (+/-9.7) in LSIL, 315 (+/-31) in HSIL, and 413 (+/-32) in squamous cancers. We conclude that increasing cervical atypicality is associated with a decrease in apoptosis. We hypothesize from our data that one factor involved in the progression of neoplasia in the uterine cervix is a decrease in the rate of normal cellular deletion.

Apoptosis↗

PubMed1996

Renal artery smooth muscle is refractory to contraction by angiotensin II.

The vasomotor responses of vascular smooth muscle from different vascular smooth muscle beds have not been well characterized. The purpose of this study was to compare the contractile responses of vascular smooth muscle from two vascular beds, the peripheral vascular bed (carotid artery) and the visceral vascular bed (renal artery) to vasoactive agonists. Fresh bovine carotid and renal artery smooth muscle contractile responses to serotonin, endothelin, angiotensin, and dopamine were determined in a muscle bath. Serotonin and dopamine cause rapidly developing sustained contractions in carotid and renal artery smooth muscle. The magnitude of the contractile response to serotonin is significantly greater in carotid artery and the magnitude of the response to dopamine is similar between carotid and renal artery. Endothelin induces a slowly developing sustained contraction of greater magnitude in renal artery. Angiotensin II causes transient contractile responses in carotid artery but renal artery smooth muscle is uniquely refractory to angiotensin stimulation. This lack of response to angiotensin II may be protective in the role of the kidney in regulating blood pressure through the renin-angiotensin system. Differences in receptor expression or affinity or in postreceptor cellular signaling events may account for these differential responses to endogenous vasoactive agonists.

Angiotensin II↗

PubMed1996

Regional differences in albuminuria among American Indians: an epidemic of renal disease.

Albuminuria is a risk factor for renal and cardiovascular disease. We conducted a cross sectional survey of 4549 older American Indians in Arizona, Oklahoma and North and South Dakota of (micro)albuminuria. A range of 20.1 to 48.3% of all participants had either micro- (> or = 30 to < 300 mg albumin/g creatinine) or macroalbuminuria (> or = 300 mg albumin/g creatinine). A total of 53% of the participants were diabetic, and the prevalence in Arizona (65 to 70%) was significantly greater than the other two sites. Prevalence of micro- and macroalbuminuria were significantly higher among those who were older, diabetic or hypertensive, and participants from Arizona. Even normotensive, nondiabetic Arizona Indians had higher prevalence rates than similar participants elsewhere. Higher prevalence rates of micro- and macroalbuminuria were also found among Arizona participants than participants with similar degrees of glucose intolerance from the other two sites. Indians reporting the greatest degree of Indian blood were more likely to have abnormal albuminuria (P < 0.0001). The duration of diabetes, fasting plasma glucose, systolic blood pressure, fibrinogen and Indian heritage were independently associated with micro- or macroalbuminuria. The association of albuminuria with subsequent ESRD, cardiovascular morbidity and overall mortality suggests that these American Indians will face a large disease burden. The correlation with reported Indian blood implies a strong component of genetic susceptibility, possibly independent of diabetes.

Aged↗

PubMed1996

Induction of ovulation with the sole use of clomiphene citrate in late-onset 21-hydroxylase deficiency.

Late-onset 21-hydroxylase deficiency (21-OHD) is a congenital enzymatic defect in the glucocorticoid and mineralocorticoid steroidogenic pathways. The manifestations, including hirsutism and infertility, usually occur at puberty or young adulthood. In infertile, anovulatory women with late-onset 21-OHD, the usual therapy is glucocorticoids for ovulation induction. In this case, we report the sole use of clomiphene citrate to induce ovulation in a patient with late-onset 21-OHD. A hirsute and oligomenorrheic woman was diagnosed as having polycystic ovary syndrome at age 25. Her hirsutism responded to oral contraceptives. At age 31, she was given clomiphene citrate alone for ovulation induction and conceived in her fourth cycle. At age 36, because of increased hirsutism she was diagnosed with late-onset 21-OHD by an ACTH stimulation test. The induction of ovulation in late-onset 21-OHD patients has been with glucocorticoids. Given the success in inducing ovulation with clomiphene citrate alone in this patient with well-documented late-onset 21-OHD, it may be worthwhile to study the sole use of clomiphene citrate for ovulation induction in these patients.

17-Hydroxycorticosteroids↗

PubMed1996

Immunohistochemical localization of transforming growth factor-alpha, epidermal growth factor (EGF), and EGF receptor in the human fetal ovary.

Peptide growth factors are thought to be involved in adult ovarian regulatory functions. However, little is known about the role of growth factors in human fetal ovarian development. This study is an attempt to identify and localize transforming growth factor-alpha (TGF alpha), epidermal growth factor (EGF), and EGF receptor (EGF-R) in human fetal ovaries. Ovaries were obtained from first and second trimester elective abortuses. Immunohistochemistry was performed on paraffin sections of these specimens after fixation. We examined the sections microscopically using the specific antibodies against TGF alpha, EGF, and EGF-R. Phosphate-buffered saline and preimmune IgG were used as negative controls. First and second trimester ovaries stained positively for all three proteins. Staining was significantly more intense in the oocytes than in the stroma. Negative controls did not stain. These results combined with our previous demonstration of messenger ribonucleic acid for these growth factors suggest roles for TGF alpha, EGF, and EGF-R in human fetal ovarian development. The strong staining in the oocytes suggests a possible autocrine or paracrine role of these growth factors in human oocyte growth in utero.

Epidermal Growth Factor↗

PubMed1995

Cardiovascular disease risk factors among American Indians. The Strong Heart Study.

The Strong Heart Study, a study of cardiovascular disease among American Indians, was conducted to determine cardiovascular disease rates and the prevalence of risk factors among members of 13 tribal groups in South Dakota/North Dakota (SD/ND), southeastern Oklahoma, and Arizona. From 1989 to 1992, 4,549 tribal members aged 45-74 years (62% of eligible participants) were surveyed and examined for cardiovascular disease and its risk factors. Mean total cholesterol concentrations were over 20 mg/dl lower among the men and 27 mg/dl lower among the women than national mean levels for the same age groups. Cholesterol levels varied by tribal group; Arizona Indians had mean levels more than 20 mg/dl lower than those of SD/ND Indians. The prevalence of hypercholesterolemia was almost twice as high among SD/ND Indians as among Arizona Indians, but the rates for all three groups were much lower than total US rates (all races). Mean levels of high density lipoprotein cholesterol were lower among Indian men and women than in the US population as a whole. The prevalence of hypertension among Arizona and Oklahoma Indians was higher than that for the entire United States. SD/ND Indians had significantly lower mean blood pressures and prevalence rates of hypertension than Oklahoma and Arizona Indians and the United States as a whole. The prevalence of cigarette smoking was higher for all Indian groups except Arizona women in comparison with US rates. Smoking rates were highest in SD/ND and lowest in Arizona. Indian smokers smoked fewer cigarettes per day than the average US smoker. Arizona Indians had the highest prevalence of diabetes mellitus; over 60% of those participants were diabetic. In Oklahoma and SD/ND, one third of the men and over 40% of the women were diabetic. In addition, 13-20% of the participants had impaired glucose tolerance. Proteinuria was also a common problem; almost half of the Arizona Indians had micro- or macroalbuminuria, and 20% of Oklahoma and SD/ND Indians had significant proteinuria. The prevalence of obesity was high in all three groups, with Arizona Indians having the highest rates and the highest mean body mass indices. The prevalence of current alcohol use was lower among Indians than in the nation as a whole, but binge drinking was common among those who used alcohol. These results indicate that cardiovascular disease risk factors vary significantly among tribal groups. Prevention programs tailored toward decreasing the prevalence of risk factors are recommended for long-term reduction of cardiovascular disease rates in American Indian communities.

Aged↗

PubMed1995

Growth factor receptor messenger RNA expression in human fetal brain regions.

OBJECTIVE: To analyze growth factor receptor expression in the human fetal brain. METHODS: Messenger RNA was prepared from six regions of the fetal brain from three 21-22-week abortuses and used as templates for reverse transcription. Polymerase chain reaction (PCR) was used to amplify the complementary DNA for each of the six brain regions. Amplified PCR DNA fragments were analyzed by agarose gel electrophoresis. Restriction endonuclease digestion was used to confirm the identity of the amplified PCR fragments. RESULTS: Polymerase chain reaction amplified DNA fragments consistent with expression of the insulin, insulin-like growth factors I and II, fibroblast growth factor (FGF), transforming growth factor-beta, and epidermal growth factor receptors were detected in each area of the human fetal brain studied. Of the two known insulin receptor subtype sequences, only the smaller (exon 11-) form was detected. We detected both the intact and the 267 base-deleted alternatively spliced forms of the FGF receptor. CONCLUSION: All six of the receptor messenger RNAs studied were detected in the second-trimester human fetal brain. In addition, alternative splicing of the messenger RNA was noted for the FGF and insulin receptors. This report demonstrates growth factor receptor expression and alternate splicing in specific regions of the human fetal brain. These data suggest that growth factor influence on fetal brain development may be mediated through specific growth factor receptors.

Brain↗

PubMed1995

beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding.

A central issue in the pathogenesis of Alzheimer's disease (AD) is the relationship between amyloid deposition and neurofibrillary tangle formation. To determine whether amyloid fibril formation affects the phosphorylation state of tau, primary cultures of fetal rat hippocampal and human cortical neurons were treated with beta-amyloid (beta A) in a soluble, amorphous-aggregated, or fibrillar form. Fibrillar beta A, but not soluble or amorphous-aggregated beta A, markedly induces the phosphorylation of tau at Ser-202 and Ser-396/Ser-404, resulting in a shift in the tau M(r) in human cortical neurons. Hyperphosphorylated tau accumulates in the somatodendritic compartment of fibrillar beta A-treated neurons in a soluble form that is not associated with microtubules and is incapable of binding to microtubules in vitro. Dephosphorylation of beta A-induced tau restores its capacity to bind to microtubules. Thus, amyloid fibril formation alters the phosphorylation state of tau, resulting in the loss of microtubule binding capacity and somatodendritic accumulation, properties also exhibited by tau in the AD brain. Amyloid fibril formation may therefore be a cause of abnormal tau phosphorylation in AD.

Amyloid beta-Peptides↗

PubMed1995

Kinase activation and smooth muscle contraction in the presence and absence of calcium.

PURPOSE: The intracellular signalling mechanisms that modulate the sustained vascular smooth muscle contractions that occur with vasospasm are not well understood. The purpose of this investigation was to examine cell signalling mechanisms that account for sustained vascular smooth muscle contraction, independent of increases in intracellular Ca2+ concentrations ([Ca2+]i). METHODS: Fresh bovine carotid artery smooth muscles contractile responses were examined in a muscle bath. [Ca2+]i was depleted by use of the extracellular Ca2+ chelator, ethylene glycol-bis(beta-aminoethylether) N,N,N',N'-tetraacetic acid and the intracellular chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid. RESULTS: In Ca(2+)-free conditions, depolarizing the membrane with high extracellular KCI failed to elicit a contraction. In addition, in Ca(2+)-free conditions the ([Ca2+]i) was less than 10 nmol/L as determined with the Ca(2+)-indicator, Fura 2. The protein kinase C (PKC) activator, phorbol 12, 13-dibutyrate (PDBu), induced slowly developing sustained contractions in bovine carotid artery smooth muscle, and the magnitude of the contractile response to PDBu (10 nmol/L to 10 mumol/L) was the same in the presence and absence of Ca2+. PDBu induced contractions in Ca(2+)-free conditions were not inhibited by the myosin light chain kinase inhibitor, ML-9 (50 mumol/L), but were inhibited by the PKC inhibitor, staurosporine (50 nmol/L). CONCLUSIONS: These data suggest that vascular smooth muscle contractions can occur under conditions where the [Ca2+]i is low and fixed and that these contractions may be mediated by PKC.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1995

Ontogeny of the estrogen receptor in the human fetal uterus.

The role of estrogen and its receptor in the development of the human fetal reproductive tract is unknown, but it may be involved in uterine maturation. In mouse and guinea pig uteri, studies have identified estrogen receptor (ER) protein during the fetal period. In the human, there are no published data regarding the ER during fetal uterine development. The purpose of this study was to investigate the pattern of ER gene and protein expression in the human fetal uterus. Uteri were obtained from abortuses (n = 43; range, 10-24 weeks gestation) of women undergoing elective termination of pregnancy. Reverse transcription-polymerase chain reaction was performed with whole uteri as well as cultured fetal uterine stroma-like cells (n = 15). Immunolocalization studies were performed on frozen uterine sections using the H222 monoclonal antibody (Abbott Laboratories) directed against the ER (n = 20). Western blotting was used to confirm the identity of the ER protein (n = 3). Ligand binding studies were performed using radiolabeled [3H]estradiol (n = 5). Using reverse transcription-polymerase chain reaction, a 263-basepair DNA fragment corresponding to the ER was consistently present in uteri after 15 weeks gestation. By immunohistochemistry, the ER is expressed within the uterine mesenchyme in a discrete cylindrical pattern at the interface of the differentiating endometrial stroma and myometrium. Western blotting confirmed the presence of a protein of an apparent mol wt of 66 kilodaltons, the predicted size of the ER. Ligand binding studies for the ER gave a value less than 8 fmol/mg protein. In summary, the ER gene is expressed in the uterus beginning in the early second trimester during fetal development. ER protein is localized in a discrete cylindrical pattern within the developing uterus. The highly specific location of the ER protein together with the messenger ribonucleic acid data suggest a role for the ER in differentiation of the primitive uterine mesenchyme into stromal and myometrial compartments.

Base Sequence↗

PubMed1995

Diabetes and impaired glucose tolerance in three American Indian populations aged 45-74 years. The Strong Heart Study.

OBJECTIVE: To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry. RESEARCH DESIGN AND METHODS: This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio. RESULTS: A total of 4,549 eligible participants were examined, and diabetes status was determined for 4,304 (1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status. CONCLUSIONS: Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs should be expanded to include those with IGT to improve glycemic control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.

Age Factors↗

PubMed1995

Baboon corpus luteum: epidermal growth factor receptor messenger ribonucleic acid expression during early, midluteal, and late luteal phases.

OBJECTIVE: To determine the presence and compare the relative abundance of messenger RNA for epidermal growth factor receptor (EGFR) in baboon corpora lutea of different luteal ages. DESIGN: Prospective controlled nonhuman primate study. SETTING: Animal facility in an academic research institution. PARTICIPANTS: Six adult female baboons with well-defined regular menstrual cycles. Stage of the menstrual cycle was determined by observation and scoring of perineal turgescence. The day of maximal turgescence was referred to as the day of LH surge. INTERVENTION: Ten corpora lutea were obtained by luteectomy during early (LH + 1 to 5 days, n = 3), midluteal (LH + 6 to 10 days, n = 3), and late (LH + 11 to 15 days, n = 4) luteal phases. MAIN OUTCOME MEASURE: Relative levels of messenger RNA for EGFR as determined by ribonuclease protection assay using RNA probe generated from complementary DNA for human EGFR. RESULTS: Messenger RNA for EGFR is present in baboon corpora lutea with relative levels of 0.51 +/- 0.18 (mean +/- SEM) in the early, 0.43 +/- 0.17 in the midluteal, and 0.50 +/- 0.17 arbitrary units in the late luteal phase. CONCLUSION: Baboon corpus luteum is a site of EGFR production; the levels of its messenger RNA did not change appreciably throughout the luteal phase.

Animals↗

PubMed1994

Localization and timing of appearance of insulin, insulin-like growth factor-I, and their receptors in the human fetal müllerian tract.

OBJECTIVE: The factors that regulate fetal müllerian tract development are still unknown. Insulin and insulin-like growth factor-I are peptides postulated to serve as autocrine or paracrine regulators of cell activity. We have previously demonstrated that messenger ribonucleic acid for insulin and insulin-like growth factor-I receptors are expressed in fetal uterine tissues. We undertook this study to determine by immunohistochemical techniques the exact location of these two growth factors and their receptors in the human fetal uterus. STUDY DESIGN: We obtained freshly discarded human fetal uteri (n = 12) between 15 and 22 weeks of gestation from elective pregnancy terminations. Frozen-section specimens were incubated with antibodies against insulin, insulin-like growth factor-I, insulin receptor, and insulin-like growth factor-I receptor. These sections were then incubated with a second antibody conjugated to fluorescein isothiocyanate and examined under phase and fluorescent microscopy. RESULTS: The fetal endometrium at 19 and 22 weeks of gestation contained insulin, insulin-like growth factor-I, insulin receptor, and insulin-like growth factor-I receptor. The distribution of immunofluorescence in the endometrium is similar for both insulin and its receptor. The same pattern of immunostaining was likewise demonstrated for insulin-like growth factor-I and its receptor. CONCLUSION: The localization of these growth factors and their receptors, combined with our previous messenger ribonucleic acid data, suggest an autocrine or paracrine role for insulin and insulin-like growth factor-I in the developing human fetal müllerian tract.

Embryonic and Fetal Development↗

PubMed1994

The electrocardiographic effects of cetirizine in normal subjects.

OBJECTIVE: To establish whether the antihistamine cetirizine has the potential to prolong the QTc interval in normal volunteers at up to six times the usual recommended dose. METHODS: Twenty-five healthy volunteers were studied in a prospective, double-blind crossover design conducted on inpatients in a Clinical Research Center. The primary end point of the study was QTc prolongation on the surface electrocardiogram (ECG). Plasma concentrations of cetirizine were also measured for pharmacokinetic analysis. The end point for the pharmacokinetic analysis was the dose/area under the concentration-time curve (apparent clearance of an oral dose). The subjects received the following three treatments in random sequence: placebo, 20 mg/day cetirizine, and 60 mg/day cetirizine for 7 consecutive days. A series of baseline ECGs was recorded over 2 days before each treatment, while the subject receiving placebo. ECG effects of the treatments were then compared with the baseline ECGs. RESULTS: Analysis of variance showed no difference between the treatment groups (placebo, 20 mg cetirizine, and 60 mg cetirizine every day) in effect on QTc compared with baseline. A paired Student t test showed no difference in dose/area under the concentration-time curve between the 20 mg/day and 60 mg/day dosing groups at steady state. CONCLUSION: In healthy volunteers, cetirizine does not prolong the QTc interval at doses of up to six times the usual recommended dose.

Adult↗

PubMed1994

In situ localization of apoptosis in the rat ovary during follicular atresia.

Apoptosis is a type of physiologic cell death that occurs in many tissues and be regulated by peptide growth factors. Recent studies indicate that apoptosis occurs in the ovary during follicular atresia in several animal species, including the rat, pig, chicken, baboon, and rabbit. The purpose of this study was to demonstrate, through in situ identification of apoptotic cells in intact ovarian sections, the sites in which apoptosis occurs in the rat ovary in different functional states. We evaluated the presence of apoptosis in three models: immature rats, eCG-treated rats and adult cycling rats. Paraffin ovarian sections were pretreated with proteinase K and then end-labeled with biotinylated deoxyuridine triphosphate (dUTP) by incubation with the enzyme terminal deoxynucleotidyl transferase (TDT). They were then stained through use of avidin-conjugated peroxidase with 3,3'-diaminobenzidine as the substrate. Healthy antral and preantral follicles had no staining. The nuclei of granulosa cells of preantral and antral atretic follicles were positively stained in all the animal groups. Scattered theca cells were also stained. Stromal cells were consistently negative. Positive controls were sections pretreated with DNase I; these displayed intense staining of all nuclei. Negative controls, in which either terminal TDT or its biotinylated substrate was omitted, were appropriately negative. This study represents a systematic analysis of apoptosis in the rat ovary at different functional stages and supports the hypothesis that apoptosis is involved in the process of follicular atresia.

Animals↗

PubMed1994

Limitations of electromyography and magnetic stimulation for assessing laryngeal muscle control.

The development of new phonosurgical techniques has increased the level of interest in the field of neurolaryngology. This field requires valid techniques for determining if muscle activation is normal. Laryngeal electromyography is being used more frequently to assess muscle innervation and synkinesis. Further, magnetic stimulation has been introduced as a noninvasive technique for nerve stimulation. Technical limitations that affect the clinical utility of both these techniques are reviewed: 1) difficulties obtaining selective and accurate electromyographic laryngeal muscle recordings, 2) normal variation in movement and muscle activation patterns within and between normal individuals when producing the same speech syllables, and 3) variation in laryngeal muscle response latencies between and within normal subjects during peripheral magnetic stimulation. Given the normal variation in laryngeal electromyography and magnetic stimulation response latencies, these techniques may not yet be reliable or accurate for assessing reinnervation or synkinesis following recurrent laryngeal nerve injury.

Adult↗

PubMed1994

Human fetal uterine cells: culture, characterization, and analysis of growth factor receptor gene expression.

Peptide growth factors are postulated to have a role in uterine maturation during organogenesis. The purpose of this investigation was to establish a model to study human fetal uterine development. To that end, we describe an in vitro culture system and have characterized the cell types present during the period of uterine maturation. In addition, we evaluated the pattern of growth factor receptor gene expression in these cultured cells. Uteri were dissected from human first and second trimester fetuses (n = 20). Characterization studies were performed against three intermediate filament proteins, cytokeratin, vimentin, and desmin, and against a fibroblast-associated cell surface antigen. Ribonucleic acid was extracted from pure stroma-like cultures, and reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify sequences specific for the epidermal growth factor receptor (EGF-R), fibroblast growth factor receptor (FGF-R), and the insulin receptor (I-R). Two predominant cell types were identified in the cultured fetal tissue: stroma-like cells and clusters of uterine epithelium. Immunofluorescent studies demonstrated positive expression of cytokeratin, vimentin, and a fibroblast-associated antigen in the fetal stroma-like cells, in contrast to adult stromal cells, which consistently expressed only vimentin. Using RT-PCR, the uterine cells were positive for the EGF-R, two forms of the FGF-R, and two forms of the I-R. In conclusion, we provide the first report of a human fetal cell culture system. Characterization studies of fetal stroma-like cells demonstrate immunoreactivity to vimentin, cytokeratin, and a fibroblast antigen, in contrast to the adult stromal cell, which consistently expressed only vimentin. Using RT-PCR, we found that messenger ribonucleic acids for the EGF-R and two forms of both the FGF-R and I-R are expressed. This model may be useful for studying the dynamics of human uterine development in vitro.

Antigens, Surface↗

PubMed1994

Quantitative analysis of epidermal growth factor receptor gene expression in endometriosis.

The molecular mechanisms by which endometriosis persists in locations outside the uterus are unclear. Recently, the epidermal growth factor receptor (EGF-R) has been postulated to have a role in the disease process of endometriosis. To explore this, we determined the levels of EGF-R protein and messenger ribonucleic acid (mRNA) expression in endometriotic tissues and compared the levels to that of eutopic endometrium. Using rabbit anti-EGF-R antibody, we found more intense immunohistochemical staining for EGF-R in glandular cells than in stromal cells of both endometriomas and endometriotic implants. No difference in staining intensity was noted between endometriotic tissues and eutopic endometrium. A ribonuclease protection assay was used to determine mRNA levels for EGF-R. PhosphoImager analysis revealed the following levels of mRNA for EGF-R; eutopic endometrium, 1.00 +/- 0.27 (arbitrary units; mean +/- SEM; n = 6 patients); cyst walls of endometriomas, 0.21 +/- 0.12 (n = 10 patients); endometriotic implants, 0.29 +/- 0.13 (n = 9 patients); and pelvic adhesions, 0.03 +/- 0.03 (n = 5 patients). Endometriotic tissues had significantly less mRNA for EGF-R than eutopic endometrium (P < 0.05, by Newman-Keuls test). Our findings support the hypothesis that EGF-R may be associated with the disease process of endometriosis.

Endometriosis↗