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Biomedical subjects

A Kanbour-Shakir

Publications and source records attributed to A Kanbour-Shakir.

At least 19 recordsLinked to original sources

Identification of genetic alterations related to chemoresistance in epithelial ovarian cancer.

OBJECTIVE: After the completion of primary chemotherapy, the majority of advanced ovarian cancer patients have persistent, chemoresistant disease. Comparative genomic hybridization (CGH) has been used to study genetic alterations that may be responsible for chemoresistance in ovarian cancer. CGH is a useful, genomewide screen but resolution is limited to 5-10 Mb. Recently, quantitative microsatellite analysis (QuMA), a TaqMan-based quantitative PCR technology, has been used for higher resolution of DNA copy number abnormalities. Our goal is to identify specific chromosomal aberrations correlated with platinum resistance. METHODS: Snap-frozen ovarian tissue samples taken from 22 patients with ovarian cancer between 1994 and 1998 were analyzed. Patients whose ovarian cancer actually demonstrated growth during platinum-combination treatment or no objective evidence of regression following four to six cycles of therapy were considered to have clinically defined platinum-resistant disease. QuMA was carried out at the following loci using the ABI Prism 7700 (TaqMan) instrument with a microsatellite repeat probe: D3S1553, D3S1617, D5S464, D5S630, D6S1581, D6S446, D8S557, D19S208, D20S196, DXS1068. Fisher's exact test, exact logistic regression, and the Cochran-Armitage trend test were used. Because of multiple hypothesis testing, the P values were adjusted with the Bonferroni procedure to limit the familywise error rate to at most 5%. RESULTS: Of the 22 patients, 12 (54.5%) were platinum-sensitive and 10 (45.5%) were platinum-resistant. When comparing sensitive and resistant patients, no statistically significant difference was noted among stage, grade, histology, and age (P = 0.1292, P = 1.0000, P = 1.0000, P = 1.0000, respectively). In the QuMA analysis, 10 of the 14 (71.4%) patients who had a low copy number of D6S1581 were platinum-resistant, while none of the patients with a normal or high copy number of D6S1581 were platinum-resistant. This was statistically significant when the marker data were treated as either a continuous or a categorical variable (P = 0.0410 and P = 0.0170, respectively). No other loci correlated significantly with platinum resistance. CONCLUSIONS: D6S1581 was the only genetic marker, of those examined, significantly related to chemoresistance. Patients with a loss of D6S1581 are more likely to be platinum-resistant. Identification of genetic alterations associated with platinum resistance detected by QuMA may contribute to a better understanding of clinical behavior and chemotherapy treatment options for patients.

Adenocarcinoma↗

Chemotherapy for malignant mixed Müllerian tumors of the ovary.

OBJECTIVE: The aim of this study was to review the chemotherapy experience at Magee-Womens Hospital for malignant mixed müllerian tumor (MMMT) of the ovary. Patients were treated with either paclitaxel/carboplatin (PC) outpatient chemotherapy or platinum/ifosfamide (PI) inpatient chemotherapy as first- or second-line therapy. METHODS: Thirteen patients diagnosed with MMMT of the ovary after complete surgical staging from 1990 to 1999 were studied retrospectively. Six patients received PC combination chemotherapy, of which 3 patients received PC as first-line treatment. The other 3 patients received PC as second-line therapy. Eight patients were treated with PI. Demographic data, pathology, cytoreductive surgery, treatment, and survival rates were reviewed. Complete clinical response (CR) was defined as the disappearance of all measurable disease or normalization of elevated CA 125 level after chemotherapy. Kaplan-Meier analysis was used for survival analysis. RESULTS: The median survival time of patients receiving PC was 19 months. One patient, after receiving PC as first-line treatment, demonstrated a CR and is free of disease beyond 33 months. The median survival time of patients managed with PI was 23 months. Three patients with suboptimal disease demonstrated CR after receiving PI. CONCLUSIONS: Optimal chemotherapy regimen for MMMT of ovary remains to be determined. Platinum-based chemotherapy in combination with ifosfamide or paclitaxel may be active against this rare malignancy.

Aged↗

Granulated metrial gland cells contain nitric oxide synthases during pregnancy in the rat.

Nitric oxide synthase (NOS) enzyme activity is present in rat decidua and metrial gland, and the activity decreases near the end of pregnancy. In this study, inducible and endothelial NOS isoforms were immunolocalized to rat granulated metrial gland (GMG) cells using anti-NOS antibodies proven to be isoform specific. These NOS-positive GMG cells are of the natural killer cell lineage as they stained positively for NKR-P1 cell surface receptor, and for perforin. The number of NOS-positive GMG cells corresponded with the level of decidual and metrial gland NOS enzyme activity. NOS activity declined when GMG cells containing NOS decreased in number. Uterine arteriolar vascular smooth muscle also stained positively for inducible NOS and the staining did not change with advancing gestation. Only a minority of uterine myocytes stained positively for inducible NOS and these were subjacent to the placental attachment site. Neuronal NOS immunostaining was not present in the decidua and the metrial gland.

Animals↗

A case-matched molecular comparison of extraovarian versus primary ovarian adenocarcinoma.

BACKGROUND: Extraovarian müllerian adenocarcinoma (EOM) resembles primary ovarian carcinoma (POC) both histologically and clinically, yet little is known regarding the molecular genetic characteristics of this entity. The objective of this study was to compare the expression of three molecular markers of tumor behavior in EOMs and POCs. METHODS: Forty-four patients meeting strict criteria for EOM were identified and matched to POC controls for age, stage, tumor histology and grade, cytoreductive surgery, and survival. Immunohistochemistry was used to determine overexpression of p53 and HER-2/neu. DNA content was evaluated by flow cytometry. Direct DNA sequencing of exons 5-8 of the p53 gene was performed in nine EOM tumors. Statistical comparisons were made using chi-square, Kaplan-Meier, and Mantel-Cox log rank methods. RESULTS: Overexpression of HER-2/neu was demonstrated in 59% (26 of 44) of the EOM group versus 36% overexpression (16 of 44) in the POC controls (P = 0.05). Overexpression of p53 was noted in 48% of the EOM cases, similar to the 59% incidence observed in the control group (P = 0.29). Missense mutations were found in 9 of 9 EOM tumors showing strong p53 nuclear immunostaining. No significant difference in the incidence of aneuploidy was observed when EOM cases were compared with POC controls (65% vs. 63%). High tumor grade was strongly associated with HER-2/neu overexpression in the EOM group (P = 0.002). None of the parameters studied were predictive of prognosis within the EOM and POC groups. CONCLUSIONS: Although overexpression of p53 protein, p53 gene mutations, and abnormal DNA content were similar between EOMs and POCs, EOMs demonstrated almost twice the rate of HER-2/neu overexpression. This result suggests that distinct genetic events may be responsible for malignant transformation in EOMs versus POCs.

Adenocarcinoma, Clear Cell↗

Breast care consultation center: role of the pathologist in a multidisciplinary center.

The Breast Care Consultation Center (BCCC) is a multidisciplinary center providing, in a single setting, a complete outpatient facility for women who have been diagnosed with or suspected of having breast cancer. A team of specialists are available to provide comprehensive, diagnostic (radiologist, surgeon, and pathologist), therapeutic (surgeon, radiotherapist, and medical oncologist), and support options. The pathologist, as a member of the diagnostic team, evaluates the material obtained or received at the BCCC. These include fine-needle aspirations (FNAs) obtained on-site as well as previously prepared cytohistological specimens. The pathologist renders the diagnosis following examination of the material and consultation with the multidisciplinary team. Thus, this approach is conducive for appropriate and accurate diagnosis where all data are available. In addition, the pathologist discusses the findings of each patient in the multidisciplinary conference. One thousand four hundred eighteen patients were evaluated at Magee-Womens Hospital BCCC from February 1992 through December 1994, during which time 366 FNAs were performed. The accuracy for positive diagnosis was 100%. Six negative cases had cancer on histology; these were due to sampling error (the lesion was missed). A multidisciplinary team is ideal for the evaluation of breast lesions that are suspicious for malignancy as it provides one-stop shopping and same-day diagnosis and therapeutic decisions.

Aged↗

Oral contraception and the recognition of endometritis.

OBJECTIVE: Oral contraceptive use has been associated with a lower risk of symptomatic pelvic inflammatory disease but a higher risk of chlamydial cervicitis. To explain these seemingly contradictory findings, we asked whether oral contraceptive use was more common among women with unrecognized endometritis than among women with recognized endometritis. STUDY DESIGN: A multicenter case-control study was performed. Women without signs of pelvic inflammatory disease were ascertained through contact tracing of partners with sexually transmitted diseases or through presentation with cervicitis. Women with symptomatic pelvic inflammatory disease met a set of standard clinical criteria. We compared the 43 cases without signs of pelvic inflammatory disease but with endometritis ("unrecognized endometritis") with the 111 controls with recognized pelvic inflammatory disease and endometritis ("recognized endometritis"). RESULTS: Women with unrecognized endometritis were 4.3 times (95% confidence interval 1.6 to 11.7) more likely than women with recognized endometritis to use oral contraceptives. CONCLUSION: Future studies need to fully characterize the risks and benefits of oral contraceptives in relation to sexually transmitted diseases.

Adult↗

Induction of experimental antiphospholipid antibody syndrome in PL/J mice following immunization with beta 2 GPI.

PROBLEM: Immunization with beta 2-glycoprotein I (beta 2 GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/(+2) mice following immunization with beta 2 GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of beta 2 GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J). METHOD: Three groups of seven-week female PL/J mice (12 per group) were studied. Group A was immunized with beta 2 GPI and group B with ovalbumin; group C was not not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72 +/- 0.6 and 0.699 +/- 0.25 for group A, 0.09 +/- 0.040 and 0.230 +/- 0.47 for group B, and 0.0435 +/- 0.003 and 0.119 +/- 0.26 for group C (comparing group A with groups B and C combined, P < 0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P < 0.001). The platelet counts were not significantly different among the three groups. The titer size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, by only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic role for beta 2 GPI-induced aPL in the development of experimental models of APS in PL/J mice.

Animals↗

Fine-needle aspiration cytology of metastatic ovarian carcinoma to the breast.

Metastatic ovarian carcinoma to the breast is rare. It represents a diagnostic challenge to the cytologist. It usually signifies a progressive widespread metastatic ovarian tumor with a poor prognosis. This report evaluates the breast fine-needle aspiration (FNA) cytomorphologic features of six cases of metastatic ovarian carcinoma and compares them to those reported in the literature. The cytologic features included hypercellularity, abundant papillary fragments, and necrotic background. The tumor cells showed high nuclear/cytoplasmic ratio, anisonucleosis, prominent nucleoli, and psammoma bodies in cases of serous papillary carcinoma. In addition, the clear-cell carcinoma had prominent finely vacuolated and clear cytoplasm, multinucleated giant cells, and papillary fragments with hobnail nuclei. Recognition of these unusual patterns in a breast FNA cytology should raise the suspicion of a metastatic ovarian tumor. Direct comparison between the breast FNA cytology and the original primary ovarian tumor should confirm the diagnosis. The proper diagnosis of metastatic ovarian cancer to the breast will prevent unnecessary surgical treatment and ensure the appropriate therapy.

Adenocarcinoma, Clear Cell↗

Adhesion formation from release of dermoid contents in the peritoneal cavity and effect of copious lavage: a prospective, randomized, blinded, controlled study in a rabbit model.

OBJECTIVES: To determine, in a rabbit model, whether peritoneal exposure to dermoid cyst material produces inflammation and adhesions above control levels and whether saline lavage reduces the degree of peritoneal reaction. DESIGN: A prospective, randomized, blinded, controlled study of adhesion formation. Thirty New Zealand white female rabbits were assigned randomly to five experimental groups: [1] laparoscopy with intraperitoneal injection of human dermoid material, [2] laparoscopy with intraperitoneal injection of human dermoid material and subsequent lavage to clear all visible dermoid material, [3] laparoscopy with saline lavage, [4] laparoscopy with intraperitoneal injection of human follicular fluid (antigenic control), and [5] laparoscopy alone. MAIN OUTCOME MEASURES: Six weeks after initial laparoscopy, inflammation and adhesions were scored in several categories via visual assessment (range 0 to 15) and histologic microscopic evaluation (range 0 to 24). Data were evaluated using Kruskal-Wallis and Mann-Whitney U nonparametric tests. RESULTS: For groups 1, 2, 3, 4, and 5, respectively, mean +/- SEM total inflammation-adhesion scores were 13.85 +/- 0.55, 2.90 +/- 1.15, 0 +/- 0, 1.50 +/- 1.00, and 0 +/- 0 for clinical evaluation and 16.83 +/- 1.22, 7.33 +/- 1.76, 0 +/- 0,0 +/- 0, and 0 +/- 0 for histologic evaluation. Using nonparametric tests, significant differences were found between groups in clinical and histologic scores. CONCLUSIONS: Dermoid material produces a significant peritonitis. Results of the clinical evaluation demonstrate that saline lavage brings inflammation and adhesion formation close to control levels. However, results of the histologic evaluation suggest that the decrement in inflammation as a result of lavage may be less dramatic than that found by clinical evaluation.

Animals↗

Vaginal evisceration: presentation and management in postmenopausal women.

BACKGROUND: Vaginal evisceration is a rare event, often associated with previous vaginal surgery in postmenopausal women. To date, 57 cases have been described in the world literature since 1901. STUDY DESIGN: We report three cases of vaginal evisceration and review risk factors and management described in the current literature. RESULTS: Of 60 reported cases of vaginal evisceration, 41 occurred in postmenopausal women. A common triad of previous vaginal surgery (73 percent), postmenopausal status (68 percent), and the presence of an enterocele (63 percent) was identified. Histopathologic evaluation of one case revealed a chronic vaginal-peritoneal fistula, and immunohistochemistry highlighted migration of squamous cells to multiple peritoneal serosal surfaces. This finding emphasizes the chronic nature of factors that predispose to the acute evisceration of abdominal contents. Most eviscerations were managed by primary repair of the vaginal disruption and the accompanying disorder of the pelvic floor, after assessing the viability of the prolapsed bowel and resecting any compromised segments. However, most surgeons agreed that delayed vaginal repair was preferable if the vaginal tissues appeared acutely inflamed or nonviable. CONCLUSIONS: Vaginal evisceration is primarily seen with obstetrical or postcoital trauma, but in postmenopausal women it is most often associated with a history of vaginal surgery and a pelvic support disorder. Hypoestrogenism, atrophy, and devascularization from previous surgery seem to play a significant role. Management is directed toward resecting any compromised bowel, repairing the vaginal defect, and correcting the contributing defect in the pelvic floor.

Aged↗

Inability to establish ectopic endometrium in a natural killer cell-deficient murine model. Immunologic, histologic and histochemical assessment.

OBJECTIVE: To investigate what effect natural killer (NK) cells have on the implantation of heterologous endometrial scrapings. STUDY DESIGN: Anti-asialo GM1 (AA-GM1) anti-sera have been shown to eliminate NK cell activity in various strains of rats and mice. Either AA-GM1 antibodies (+) or rabbit antiglobulin (-) was administered to beige mice (NK cell deficient) or beige control mice (not NK cell deficient of the same strain). The heterologous endometrial scrapings were prepared by scraping seven pairs of uterine horns from normal mice of the same strain. Beige and normal mice were then injected intraperitoneally every 3 days with the heterologous endometrial scraping and antibodies for a period of 50 days. The four experimental groups (n = 10 per group) can be summarized as being beige (+), beige (-), normal (+) and normal (-). RESULTS: There was no evidence of ectopic endometrial tissue in any of the four test groups by histologic examination or by using immunohistochemical staining techniques. Histologic evidence of an impaired immune response was clearly demonstrated in the beige mice receiving AA-GM1 antibodies. CONCLUSION: Using this model, a deficiency of NK cell activity did not appear to enhance the implantation of endometrial tissue on the abdominal peritoneum of mice.

Animals↗

Serous psammocarcinoma of the ovary in an adolescent female.

A rare form of epithelial ovarian carcinoma in an adolescent female is reported. Serous psammocarcinoma is a type of ovarian cancer that is characterized by extensive psammoma body formation and has not been reported in this age group. Histopathologically, this tumor exhibits stromal invasion, vascular invasion, epithelial cells with low to moderate nuclear atypia, nests of solid epithelial cells less than 15 cells in diameter, and psammoma bodies that involve at least 75% of papillae or nests of cells. The patient underwent optimal surgical debulking and nine courses of adjuvant chemotherapy with carboplatinum and cyclophosphamide and is currently disease free. The prognosis for this type of ovarian cancer is unclear, but it appears to be better than other forms of epithelial ovarian cancer.

Adolescent↗

Seminal fluid and the expression of MHC class I antigens in the placenta of the rat.

PROBLEM: To determine whether seminal fluid influences the expression of MHC class I antigens on the surface of basal trophoblast cells in the placenta of the rat. METHODS: Transfer of DA x DA embryos into a WF (allogeneic) or DA (syngeneic) recipient made pseudopregnant by hormonal treatment followed by mating with a vasectomized male (seminal fluid) or by mechanical stimulation (no seminal fluid). Antigen expression was determined by electron microscopic immunocytochemistry using the appropriate gold-labeled monoclonal antibodies. RESULTS: Seminal fluid did not affect the expression of MHC class I antigens on the surface of the basal trophoblast in either allogeneic or syngeneic matings. CONCLUSIONS: The suppression of the expression of paternal class I antigens on the surface of the basal trophoblast cells in allogeneic pregnancies most likely occurs at the genome level shortly after fertilization.

Animals↗

Normal uterine cervix: characterization of isolated lymphocyte phenotypes and immunoglobulin secretion.

PROBLEM: Isolation of viable cervical lymphocyte populations and characterization of their function in healthy tissue is necessary to understand immunity in the genital tract. METHODS: Normal, cervical tissue was digested using a multi-enzymatic digestion procedure. Lymphocytes were characterized using FACS analysis and ELISPOT analysis for immunoglobulin secreting cells. RESULTS: Following the digestion procedure, 0.16 x 10(6) +/- 0.8 cells/g of tissue with a viability of 90-98% were isolated from normal cervical tissue. FACS analysis determined that B lymphocytes were the predominant cell type in normal cervical tissue representing a significantly higher percentage than that found in peripheral blood (P = 0.015). T lymphocytes and NK cells represented a significantly lower percentage than that found in peripheral blood (P = 0.0001 and 0.026, respectively). The largest percentage of immunoglobulin secreting cells isolated were secreting IgG followed by IgA. A limited number of IgM secreting cells were detected. IgA2 secreting cells represented 34.46 +/- 4.6% of the total number of IgA plasma cells. CONCLUSION: These studies represent the first analysis of viable mononuclear cells isolated from normal cervical tissue. The results form a baseline from which it will now be possible to compare changes that occur at the cervical squamocolumnar junction in response to infection or neoplasia.

Adult↗

Pipelle endometrial sampling. Sensitivity in the detection of endometrial cancer.

OBJECTIVE: To evaluate the sensitivity of the Pipelle endometrial suction curette in the detection of endometrial carcinoma in patients with known endometrial cancer. STUDY DESIGN: A study was conducted using patients with known endometrial cancer undergoing a hysterectomy as part of a formal staging procedure. Endometrial biopsies were performed prior to each surgical procedure. Biopsy results were compared to the hysterectomy specimen for specimen adequacy and final histologic diagnosis. RESULTS: The Pipelle biopsy was adequate for analysis in 63 of 65 patients (97%). Malignancy was detected by biopsy in 54 of 65 patients, for a sensitivity of 83 +/- 5% (mean +/- SD). Of the 11 patients with false negative results, 5 had tumors present in only an endometrial polyp. Three of the 11 patients had disease localized to < 5% of the surface area of the endometrium. CONCLUSION: The Pipelle endometrial suction curette is an effective office device for evaluating patients at risk of endometrial cancer; however, tumors localized to a polyp or small area of endometrium may go undetected.

Biopsy↗

Developmental expression and anatomical localization of endothelin-1 messenger ribonucleic acid and immunoreactivity in the rat placenta: a northern analysis and immunohistochemistry study.

Endothelin-1 (ET-1) immunoreactivity and messenger ribonucleic acid (mRNA) have previously been identified in the mammalian placenta. In the present study we examined the developmental expression of ET-1 mRNA and the localization of ET-1 mRNA and immunoreactivity within the rat placenta. Placental tissues were removed from primiparous Sprague-Dawley rats on gestational days 14, 18, and 21 and processed for blot hybridization of ET-1 mRNA and immunohistochemistry of ET-1 immunoreactive peptide. Placental tissue contained a 2.3 kb size ET-1 mRNA transcript. Placental ET-1 mRNA abundance increased approximately five-fold from day 14 to 21 of gestation (p = 0.02). To localize ET-1 mRNA within the rat placenta, day 18 placentas were dissected into the basal and labyrinth layers and processed separately for blot hybridization of ET-1 mRNA. ET-1 mRNA localized to the labyrinth zone. This was confirmed by immunohistochemical staining of day 18, 20, and 21 placental tissues with an antiserum specific to ET-1. The presence of ET-1 immunoreactivity and the stage-specific increase in ET-1 mRNA in the rat placenta suggest that ET-1 may exert paracrine effects on the placenta or uterus of the pregnant rat.

Animals↗

Modulation of c-MET proto-oncogene (HGF receptor) mRNA abundance by cytokines and hormones: evidence for rapid decay of the 8 kb c-MET transcript.

The c-MET proto-oncogene product is a transmembrane tyrosine kinase receptor which was recently shown to transmit an array of important cellular responses induced by Hepatocyte Growth Factor (HGF). These biological effects include induction of mitogenesis, motogenesis, morphogenesis, metastogenesis and anti-tumor activity on a variety of epithelial cells. All of these processes are known to be associated with normal and abnormal tissue growth and development. The 190 kDa c-MET protein is encoded by a major transcript of 8 kilobases (kb), which is reported to be expressed predominantly in epithelial tissues. The expression pattern of c-MET mRNA and protein are drastically modified in many tumor tissues and cell lines. Currently, no information is available on the molecular mechanisms that regulate c-MET mRNA level. In the present communication, we report for the first time that the inflammatory cytokines such as IL-1 alpha, IL-6 and TNF-alpha, as well as TGF-beta 1, EGF, HGF and the steroidal hormones (estrogen, progesterone, tamoxifen and dexamethasone) markedly influence the steady-state levels of the 8 kb c-MET mRNA in human carcinoma cell lines derived from human tissues such as ovary, breast and endometrium. We demonstrate that c-MET receptor protein is present at high levels in primary tumors of human ovaries (clear cell carcinomas). We present evidence that the 8 kb c-MET mRNA undergoes rapid degradation with a half-life of less than 30 min and that this decay can be quickly inhibited by cycloheximide. Our results suggest that the expression of the c-met proto-oncogene resembles that of an immediate early response gene.

Cytokines↗

Differential genomic imprinting of major histocompatibility complex class I antigens in the placenta of the rat.

The RT1.A and Pa (class I) loci in the major histocompatibility complex (MHC) of the rat are genomically imprinted in the placenta, since only the paternally derived antigens are expressed. To determine whether the RT1.E (class I) locus, which defines the end of the MHC opposite RT1.A, is genomically imprinted in the placenta, two different types of crosses were studied: all possible mating combinations of the DA (AaE-) and WF (AuEu) inbred strains and various matings of the R16 (AaE-), R33 (AaEu), and R34 (AaE-) congenic recombinant strains. The results showed that the Eu locus was not imprinted. Thus, genomic imprinting can be different at two endogenous loci that are part of a multigene family in tight-linkage disequilibrium. The lack of Eu imprinting is not due to the locus' being monomorphic, since the monomorphic Pa locus is imprinted, and it is most probably not due to its distance from the imprinted RT1.A and Pa loci (0.4 cM). We suggest that the control of the imprinting may lie in the physical structure of the DNA proximate to the imprinted locus.

Animals↗