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Biomedical subjects

M D Mueller

Publications and source records attributed to M D Mueller.

At least 19 recordsLinked to original sources
PubMed2001

Purification and characterization of an immunomodulatory endometrial protein, glycodelin.

Human glycodelin is synthesized by endometrial cells in the late secretory phase and early pregnancy under hormonal regulation. Whereas the precise physiological functions of glycodelin are unknown, its expression during embryonic nidation and its inhibition of T cell proliferation suggest an immunomodulatory role. We purified human glycodelin from first trimester human decidual cytosol by using a rapid two-step high-performance liquid chromatography method and investigated its effects on human monocyte migration. Human U937 cells were used as a model of monocyte chemotaxis in Boyden chamber migration assays. N-Formyl-Met-Leu-Phe and the beta-chemokine RANTES (regulated on activation normal T cell expressed and secreted) were used as monocyte chemoattractants. Purified glycodelin inhibited monocyte migration in a dose-dependent fashion (IC50 = 550 nm). Glycodelin activity was totally reversed by heat inactivation (95 degrees C x 15 min) and neutralized by pretreatment with specific anti-glycodelin antibodies. Deglycosylated glycodelin was equipotent to intact glycodelin in the monocyte migration assay. 125I-Glycodelin binding to whole U937 cells revealed a single, saturable site with a Kd = 48 +/- 21 nm by Scatchard analysis. Cross-linking studies indicated that glycodelin binds to a high molecular mass (approximately 250 kDa) protein complex at the monocyte cell surface. Our findings support the hypothesis that glycodelin reduces the local maternal inflammatory response toward the implantation of a semiallogeneic conceptus.

Amino Acid Sequence↗
PubMed2001

Immunobiology of endometriosis.

OBJECTIVE: To provide a review of the humoral and cellular immunology of endometriosis and to discuss the rationale for future approaches to diagnosis and treatment. DESIGN: Literature survey. RESULT(S): Defective immunosurveillance in women who are destined to develop endometriosis may allow for the survival of ectopic endometrial tissue. The evidence includes endometrial cell resistance to apoptosis, perhaps through the secretion of proteins that interfere with implant recognition and/or FasL expression by stromal cells, inducing apoptosis of Fas-bearing immune cells. Although the immune response may be defective, aspects of it clearly are enhanced in endometriosis, as is seen by the generalized polyclonal B-cell autoimmune activation and secretion of immune proteins. Several cytokines, chemokines, and growth factors (including vascular growth factors) are increased in women with endometriosis. CONCLUSION(S): A complex network of locally produced cytokines modulate the growth and inflammatory behavior of ectopic endometrial implants. Proinflammatory proteins from endometriotic lesions and associated immune cells contribute to the enhanced inflammatory reaction associated with endometriosis that subserves the survival of these lesions instead of leading to their demise.

Adult↗
PubMed2000

Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta.

Vascular endothelial growth factor (VEGF) mediates angiogenic activity in a variety of estrogen target tissues. To determine whether estrogen has a direct transcriptional effect on VEGF gene expression, we developed a model system by transiently transfecting human VEGF promoter-luciferase reporter constructs into primary human endometrial cells and into Ishikawa cells, derived from a well-differentiated human endometrial adenocarcinoma. In primary endometrial epithelial cells, treatment with 17beta-estradiol (E(2)) resulted in a 3.8-fold increase in luciferase activity, whereas a 3. 2-fold induction was demonstrated for stromal cells. Our Ishikawa cells had less than 100 functional estrogen receptors (ER)/cell and were therefore cotransfected with expression vectors encoding either the alpha- or the beta-form of the human ER. In cells cotransfected with ERalpha, E(2) induced 3.2-fold induction in VEGF-promoter luciferase activity. A 2.3-fold increase was observed in cells cotransfected with ERbeta. Through specific deletions, the E(2) response was restricted to a single 385-bp PvuII-SstI fragment in the 5' flanking DNA. Cotransfection of this upstream region with a DNA binding domain ER mutant, or site-directed mutagenesis of a variant ERE within this fragment, resulted in the loss of the E(2) response. Electromobility shift assays demonstrated that this same ERE sequence specifically binds estradiol-ER complexes. These studies demonstrate that E(2)-regulated VEGF gene transcription requires a variant ERE located 1.5 kb upstream from the transcriptional start site. Site-directed mutagenesis of this ERE abrogated E(2)-induced VEGF gene expression.

Cells, Cultured↗
PubMed2000

Effects of progestins and relaxin on glycodelin gene expression in human endometrial cells.

OBJECTIVE: Glycodelin is an endometrial protein proposed to play an important role in embryonic implantation. We examined the effects of progestins and relaxin on glycodelin transcription, synthesis, and secretion. STUDY DESIGN: Northern blotting, metabolic labeling, and fluorography were used to assess glycodelin messenger ribonucleic acid and protein synthesis in endometrial tissue and cells. Luciferase reporter constructs transfected into endometrial adenocarcinoma cells (Ishikawa cells) were used to determine whether progestins or relaxin could activate the glycodelin gene promoter. RESULTS: Progestins but not relaxin stimulated glycodelin secretion in primary epithelial cell cultures. A 452-base pair fragment of the glycodelin gene promoter was activated 4.3 +/- 0.7 times normal by 10-nmol/L promegestone; however, addition of relaxin to the same construct repressed progestin-stimulate promoter activation by >30%. CONCLUSION: Glycodelin transcription, synthesis, and secretion by endometrial epithelial cells were stimulated by progestins. However, relaxin failed to stimulate production of this immunomodulatory protein and, in fact, repressed progestin-stimulated activation of the glycodelin gene promoter.

Endometrium↗
PubMed2000

Neutrophils infiltrating the endometrium express vascular endothelial growth factor: potential role in endometrial angiogenesis.

OBJECTIVE(S): To identify leukocytes within the human endometrium expressing vascular endothelial growth factor (VEGF). DESIGN(S): Prospective cohort study. SETTING(S): Healthy volunteers in an academic research environment. PATIENTS(S): Twenty-one normal cycling women without abnormal menstrual bleeding or infertility. INTERVENTION(S): Endometrial tissue collection by Pipelle de Cornier aspiration. MAIN OUTCOME MEASURES(S): Histologic, immunohistochemical (CD3, CD34, CD56, CD68, neutrophil elastase, estrogen and P receptors, VEGF), and simultaneous double immunoenzymatic labeling analysis of VEGF-positive cells within the human endometrium. RESULT(S): Ten endometrial samples were obtained in the proliferative (cycle days 5-10) and 11 samples in the secretory phase (cycle days 15-26). Immunohistochemical analyses showed the expected distribution of the different leukocyte cell types. Besides epithelial and stromal endometrial cells, the predominant cells that stained for VEGF were neutrophil granulocytes. Neutrophils were more abundant in the secretory phase but they expressed neither estrogen-a nor P receptors. CONCLUSION(S): Neutrophil granulocytes infiltrating the human endometrium express VEGF and regulate cyclical endometrial vascular proliferation. Ovarian steroids indirectly influence neutrophil migration.

Adult↗
PubMed2000

Glycodelin: a pane in the implantation window.

Glycodelin is an endometrial protein with proposed immunomodulatory activity during human embryonic nidation. In this review we describe the effects of ovarian hormones on glycodelin transcription, synthesis, and secretion by human epithelial cells and focus on the importance of glycodelin in implantation. We demonstrate that glycodelin transcription, synthesis, and secretion by human epithelial cells are stimulated by progestins and antiprogestins but not by estrogen. Sequences localized within a 403-base-pair region flanking the 5' human glycodelin gene promoter appear to be responsible for transcriptional activation of this gene mediated by progesterone receptor-ligand complexes. Relaxin, purported to enhance glycodelin production in vivo and in prior in vitro studies, had no stimulatory effect on the expression of this gene in vitro in our models.

Cells, Cultured↗
PubMed2000

Ovarian steroid and cytokine modulation of human endometrial angiogenesis.

A key mechanism underlying the cyclical growth of the endometrium is its ability to regenerate a vascular capillary network. In normal cycling human endometrium, angiogenesis is influenced by both endocrine and paracrine factors. Hormonal manipulation of the endometrium, such as that occurring during the use of steroidal contraception, appears to result in capillary proliferation and fragility. As a consequence of these vascular changes, contraceptive users may be predisposed to unpredictable uterine bleeding, which is responsible for the high frequency of contraceptive discontinuation. In this paper we address mechanisms responsible for vascular endothelial cell proliferation in normal and contraceptive steroid-exposed endometria. We propose that regulation of endometrial angiogenesis is mediated indirectly, via steroid and cytokine actions on vascular endothelial growth factor (VEGF), and we present data indicating that VEGF expression in normal endometrial stromal cells is increased by oestrogens and progestins. Three proinflammatory cytokines with angiogenic effects in other systems (i.e. interleukin-1beta, tumour necrosis factor-alpha and interferon-gamma) do not appear to up-regulate VEGF expression in normal endometrial stromal cells. Well-characterized in-vitro models in conjunction with immunohistochemistry provide useful experimental systems to study endometrial neovascularization under physiological conditions and in those potentially perturbed via the use of contraceptive steroids.

Biopsy↗
PubMed1999

Three-dimensional laparoscopy. Gadget or progress? A randomized trial on the efficacy of three-dimensional laparoscopy.

BACKGROUND: This study was designed to compare conventional laparoscopy with three-dimensional (3-D) laparoscopy. METHOD: Thirty candidates, 20 inexperienced and 10 experienced in operative laparoscopy, executed standardized exercises on a pelvitrainer. The candidates were randomized to two groups. Group A executed the exercises first with the conventional and then with the three-dimensional system. Group B accomplished the exercises in the reverse sequence. At the end of the exercises, the candidates answered specific questions about the two systems. RESULTS: A total of 21 h 6 min 6 sec of laparoscopic exercises were analyzed-10 h 8 min 1 sec with the conventional and 10 h 58 min 5 sec with the three-dimensional system (p = 0.38). Group A required 12 h 26 min 56 sec to perform all the exercises. There was no statistically significant difference from group B, where the candidates needed 8 h 39 min 10 sec (p = 0.14). Neither were there any differences in the number of failed attempts between the two groups. There were also no statistical difference when the results obtained from the candidates without experience in laparoscopy and the participants experienced in operative laparoscopy were analyzed separately. Both the inexperienced and the experienced candidates became tired earlier, had more headaches, and needed extra time to adapt to the 3-D system. CONCLUSION: When analyzed in a standardized fashion, 3-D laparoscopy does not have any significant advantages over conventional laparoscopy.

Adult↗
PubMed1999

Prenatal diagnosis of a lean umbilical cord: a simple marker for the fetus at risk of being small for gestational age at birth.

OBJECTIVE: The purpose of this study was to investigate whether the prenatal diagnosis of a 'lean' umbilical cord in otherwise normal fetuses identifies fetuses at risk of being small for gestational age (SGA) at birth and of having distress in labor. The umbilical cord was defined as lean when its cross-sectional area on ultrasound examination was below the 10th centile for gestational age. METHOD: Pregnant women undergoing routine sonographic examination were included in the study. Inclusion criteria were gestational age greater than 20 weeks, intact membranes, and singleton gestation. The sonographic cross-sectional area of the umbilical cord was measured in a plane adjacent to the insertion into the fetal abdomen. Umbilical artery Doppler waveforms were recorded during fetal apnea and fetal anthropometric parameters were measured. RESULTS: During the study period, 860 patients met the inclusion criteria, of whom 3.6% delivered a SGA infant. The proportion of SGA infants was higher among fetuses who had a lean umbilical cord on ultrasound examination than among those with a normal umbilical cord (11.5% vs. 2.6%, p < 0.05). Fetuses with a lean cord had a risk 4.4-fold higher of being SGA at birth than those with a normal umbilical cord. After 25 weeks of gestation, this risk was 12.4 times higher when the umbilical cord was lean than when it was of normal size. The proportion of fetuses with meconium-stained amniotic fluid at delivery was higher among fetuses with a lean cord than among those with a normal umbilical cord (14.6% vs. 3.1%, p < 0.001). The proportion of infants who had a 5-min Apgar score < 7 was higher among those who had a lean cord than among those with normal umbilical cord (5.2% vs. 1.3%, p < 0.05). Considering only patients admitted in labor with intact membranes and who delivered an appropriate-for-gestational-age infant, the proportion of fetuses who had oligohydramnios at the time of delivery was higher among those who had a lean cord than among those with a normal umbilical cord (17.6% versus 1.3%, p < 0.01). CONCLUSION: We conclude that fetuses with a lean umbilical cord have an increased risk of being small for gestational age at birth and of having signs of distress at the time of delivery.

Adult↗
PubMed1999

Vascular endothelial growth factor in reproductive biology.

The critical role of angiogenesis in embryology and tumor biology has been recognized for more than 20 years. However, the fact that neovascularization is essential to processes in mammalian female reproduction has only recently been appreciated widely. In this review we focus on a single angiogenic growth factor, vascular endothelial growth factor. As scientists have discovered in many aspects of cell biology, multiple and redundant signaling pathways have evolved in nature, presumably to protect essential biological functions from inactivating diseases or mutations. Despite this redundancy, some factors are of hierarchical importance. Vascular endothelial growth factor appears to be such a factor in the regulation of angiogenesis.

Endometrium↗
PubMed1999

Decrease of serum endothelin levels with postmenopausal hormone replacement therapy or tibolone.

Endothelin is the most potent vasoconstrictor peptide known to date. Hormone replacement therapy (HRT) with estrogen reduces plasma endothelin levels. We measured endothelin in 51 postmenopausal patients before and during HRT. Patients were randomly allocated to receive either oral tibolone, oral or transdermal 17 beta-estradiol. A group of comparable volunteers served as controls. After 24 months, endothelin levels decreased in all treatment groups: tibolone, 18.2%; oral 23.1%; transdermal, 20.8%. Endothelin levels increased in the controls by 36.6% (p < 0.01). Tibolone decreases endothelin levels to a similar degree as conventional estrogen-progestogen-replacement therapy. These data provide another potential mechanism supporting the cardioprotective effects of tibolone.

Administration, Cutaneous↗
PubMed1998

Is laparoscopic oophorectomy rational in patients with breast cancer?

BACKGROUND: Unsuspected malignancy remains a problem for the laparoscopic surgeon. The aim of this study was to evaluate the risk of ovarian micrometastasis in patients with breast cancer who undergo laparoscopic oophorectomy. METHODS: We analyzed 25 premenopausal women with breast cancer who underwent therapeutic laparoscopic oophorectomy. The patients were subdivided into the following two groups according to ovarian pathology: group A with and group B without breast carcinoma micrometastasis. We then reviewed the follow-up data for both groups, with special attention to metastasis of the abdominal wall. RESULTS: Twelve of 44 ovaries removed by laparoscopy showed ovarian breast carcinoma micrometastasis. There were no predictive factors of micrometastasis. After a mean follow-up of 38.1 months (95% CI: 29.2-46.9 months), none of the patients with proven micrometastasis developed metastasis of the abdominal wall, and the 21 puncture sites were inconspicuous. CONCLUSIONS: Although 32% of patients may have unexpected ovarian micrometastasis, laparoscopic oophorectomy in patients with breast cancer remains a safe procedure.

Abdominal Muscles↗
PubMed1997

Higher rate of fetal acidemia after regional anesthesia for elective cesarean delivery.

OBJECTIVE: To determine the prevalence of fetal acidemia associated with regional anesthesia for elective cesarean delivery in healthy paturients with uncomplicated singleton term pregnancies. METHODS: This was an epidemiologic study using the data base of the Swiss obstetric study group (Arbeitsgemeinschaft Schweizerischer Frauenkliniken). After the exclusion of cases with extraneous factors that may have affected the health of the neonate, we analyzed the umbilical artery pH, Apgar score, and other neonatal outcome measures after cesarean delivery with reference to the anesthetic technique. RESULTS: From 1985 to 1994, 327,763 deliveries, including 40,858 (12.47%) by cesarean, were registered in the data base. Of these, 5806 patients fulfilled the study criteria. The study population included 1002 spinal, 2155 epidural, and 2649 cases of general anesthesia. The frequency of fetal acidemia (pH less than 7.10) was significantly increased in the spinal-anesthesia group (odds ratio [OR] 4.67; 95% confidence interval [CI] 2.73, 8.01) and in the epidural group (OR 2.39; 95% CI 1.42, 4.04) compared with the general-anesthesia group. CONCLUSION: The rate of fetal acidemia is significantly increased after regional anesthesia. This risk must be judged in light of the risks inherent with general anesthesia.

Adult↗
PubMed1996

Cigarette smoking among U.S. adults by state and region: estimates from the current population survey.

BACKGROUND: Cigarette smoking is responsible for at least one third of all cancer deaths annually in the United States. Few sources exist in the peer-reviewed literature documenting state and regional differences in smoking behavior, despite the fact that cancer prevention and control efforts are increasingly being implemented below the national level. PURPOSE: Our goals were to determine smoking prevalence rates among men and women, by region, and for each of the 50 states and the District of Columbia from census survey data collected in 1992 and 1993 and to compare these rates with rates determined in 1985. METHODS: Every month, the U.S. Bureau of the Census collects labor force statistics on more than 100000 individuals on its Current Population Survey (CPS). For the September 1992, January 1993, and May 1993 CPS, the National Cancer Institute sponsored a 40-item Tobacco Use Supplement. The definition of a current smoker changed slightly between 1985 and 1992-1993. For the 1985 CPS, individuals were considered current smokers if they had smoked 100 cigarettes in their lifetime and were smoking at the time of interview; for the 1992-1993 CPS, current smokers included anyone who had smoked 100 cigarettes and was currently smoking every day or just on some days. We calculated current smoking rates (every day and some days combined) based on more than a quarter million adults (n = 266988) interviewed in 1992-1993. RESULTS: Substantial geographic variation exists in rates of current cigarette use among adults within the United States. In general, adults in the southern United States have higher rates of smoking and adults in the western states have lower rates of smoking and adults in the rest of the country, although differences in smoking behavior between men and women and among various racial and ethnic populations strongly influence these patterns. Only two states, Kentucky and West Virginia, exhibited adult smoking rates (men and women combined) of 30% or higher in 1992-1993; in contrast, in 1985, such rates were reported from 20 states. The only states in which the prevalence was below 20% in 1992-1993 were Utah (17.1%) and California (19.5%). Rates approaching 20% were reported from New Jersey (20.7%), Massachusetts (21.5%), and Nebraska, New York, and Hawaii (22.0% each) in 1992-1993. Rhode Island experienced the greatest relative decline in smoking prevalence from 1985 to 1992-1993, with a calculated relative change of -30.7% (based on a change in rate from 33.5% to 23.2%), followed by Delaware (-25.9%) the District of Columbia and New Jersey (-23.9% each), Connecticut (-23.2%), California (-22.9%), Alaska (-22.8%), Georgia (-22.6%), Massachusetts (-22.1%), and New York (-22.0%). CONCLUSIONS: Smoking rates are not uniform in the United States but vary considerably from state to state, even within the same region of the country. The CPS is the only mechanism currently capable of simultaneously monitoring smoking trends nationally, regionally, and on a state-by-state basis.

Age Distribution↗
PubMed1995

[Hemoperitoneum due to coitus without vaginal lesions].

A 27-year-old female patient presented in our clinic 14 hours after onset of acute lower abdominal pain during sexual intercourse. Sonography showed ascites around the uterus and structures suspected to be clotted blood. Diagnostic laparoscopy showed in the abdomen about 400 ml of clotted blood: sources of bleeding were small injuries of the left sacro-uterine ligament. Therapy was not necessary, except careful rinsing since hemostasis was already complete. It is important to consider abdominal injuries in cases of abdominal pain after sexual intercourse, even if vulvar or vaginal injuries are absent.

Abdominal Injuries↗
PubMed1995

An evaluation of laparoscopic adhesiolysis in patients with chronic abdominal pain.

The purpose of this prospective study was to determine whether laparoscopic adhesiolysis ameliorates chronic abdominal pain in patients with abdominal adhesions. Forty-five patients with chronic abdominal pain lasting for more than 6 months but with no abnormal findings other than adhesions found at laparoscopy underwent laparoscopic adhesiolysis. Thirty-six patients (80%) were available for follow-up after a median time interval of 10 months (range: 6-36 months). Seventeen patients (47.2%) were free from abdominal pain and 13 patients (36.1%) reported significant amelioration of their pain. Six (16.6%) patients had no amelioration. Twenty-nine patients (80.6%) judged the outcome of the operation to be good or beneficial and 35 (97.2%) said that they would undergo the operation a second time if that were necessary. Laparoscopy is an effective tool for the evaluation of patients with chronic abdominal pain, and laparoscopic adhesiolysis cures or ameliorates chronic abdominal pain in more than 80% of patients.

Abdominal Pain↗
PubMed1995

[Ultrasound diagnosis of epignathus in the 17th week of pregnancy. Case report and review of the literature].

An epignathus was found by routine screening ultrasound examination in the 17th week of pregnancy. Epignathi are teratomas in the oral cavity and are rarely found. The detection of an epignathus in the first half of pregnancy was described only three times in literature. The teratoma may also invade the cerebrum and is associated with a polyhydramnios and elevated alphafetoprotein. If the diagnosis is made in the first half of pregnancy a induced abortion is to be discussed.

Adult↗