Acute myelogenous leukemia in a patient receiving etanercept for psoriasis.
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Adult↗
Biomedical subjects
Kiarash Khosrotehrani
Publications and source records attributed to Kiarash Khosrotehrani.
Presence of chimeric maternally derived keratinocytes in cutaneous inflammatory diseases of children: the example of pityriasis lichenoides.
During pregnancy, maternal cells may enter the fetal circulation and persist until adulthood. The fate of these cells remains unknown. As unexplained T-cell-mediated conditions such as pityriasis lichenoides (PL) may occur in children, we aimed at identifying maternal cells in lesional skin of PL and controls. Archived skin biopsy specimens from young males with PL, atopic dermatitis, or normal skin were scanned for the presence of female (presumably maternal) cells using fluorescence in situ hybridization (FISH) with X and Y chromosome-specific probes. Phenotyping of maternal cells relied on FISH combined with anti-CD45, anti-CD1a, or anti-cytokeratin labelling, identifying leukocytes, Langerhans cells, and keratinocytes, respectively. Maternal cells were found in PL (11/12) and controls (4/7), but their average frequency was higher in PL: 99 per million cells as compared to 5 per million cells in controls (P = 0.005). In the epidermis, the maternal microchimeric cells were labelled by anti-cytokeratin in all cases. We identified maternally derived keratinocytes in the skin of male children with inflammatory skin disorders. These cells may either help repair the damaged skin or home initially in the skin and trigger a host (child) versus graft (mother) disease.
Antigens, CD1↗
Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse.
Fetal cells circulate in pregnant women and persist in blood and tissue for decades post-partum. The mother thus becomes chimeric. Factors that may influence such fetal cell microchimerism include histocompatibility, fetal or placental abnormalities, or a reproductive history that includes miscarriage or elective termination. Fetal cell microchimerism is associated with some maternal autoimmune diseases, such as systemic sclerosis. Moreover, a novel population of fetal cells, the pregnancy-associated progenitor cells (PAPCs), appears to differentiate in diseased or injured maternal tissue. The cellular origin of these cells is at present unknown but could be a hematopoietic stem cell, a mesenchymal stem cell, or a novel cell type. Pregnancy therefore results in the acquisition of cells with stem-cell-like properties that may influence maternal health post-partum. Rather than triggering disease, these cells may instead combat it.
Animals↗
Skin carcinoma arising from donor cells in a kidney transplant recipient.
The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.
Bowen's Disease↗
Subcutaneous neurofibromas are associated with mortality in neurofibromatosis 1: a cohort study of 703 patients.
Neurofibromatosis 1 (NF1) is a common genetic disorder with an autosomal dominant mode of inheritance, an increased morbidity and mortality, and a shorter lifespan. Although the disease is fully penetrant by the age of 8, the variability in symptoms and complications is high, even among members of the same family. The aim of this study was to identify easily recognizable clinical features that may be associated with mortality in a cohort of patients affected with NF1. We used prospectively collected data from the Neurofibromatosis Institute Database (NFID) and included in our analysis 703 patients who fulfilled the NIH diagnostic criteria for NF1. Clinical, especially dermatological features were tested as potential factors associated with mortality. Among the patients, 405 (57.6%) were children and 298 (42.4%) were adults. The mean follow-up was 2.4 years (median = 0.98, range: 0-15.3 years). Forty patients died during follow-up, mostly due to tumor development such as sarcoma (n = 18). In the adult population, subcutaneous neurofibromas (odds ratio [OR] = 3.6, 95% confidence interval (CI): [1.2-11.3], P = 0.02) and male gender (OR = 5.6, [1.5-20.9], P = 0.004) were independent predictors of mortality after adjustment for age. Among children, the presence of facial plexiform neurofibromas and pruritus were significantly associated with mortality in univariate analysis. Our study describes independent risk factors of mortality in a large cohort of adult and pediatric patients. Close follow-up should be obtained for patients presenting with subcutaneous neurofibromas.
Adolescent↗
The utility of an erythroblast scoring system and gender-independent short tandem repeat (STR) analysis for the detection of aneuploid fetal cells in maternal blood.
OBJECTIVE: The aim of this study was to determine whether fetal nucleated red blood cells (NRBCs) could be distinguished from maternal cells in peripheral blood using an erythroblast scoring system based on the unique morphological and hemoglobin staining characteristics of this cell type. Presumptive fetal NRBCs were further analyzed for the presence of paternally inherited DNA polymorphisms to prove fetal origin. METHODS: NRBCs were isolated by density gradient separation, CD15/45 depletion, and gamma hemoglobin positive selection from peripheral blood of nine women following termination of pregnancy for trisomy 21 (n=4), 18 (n=1), 13 (n=2), and other genetic abnormalities (n=2). Candidate fetal NRBCs, based on four discrete morphological and hemoglobin staining criteria, were then subjected to fluorescent PCR (polymerase chain reaction) amplification of chromosome 21 (D21S1411, D21S11) and chromosome 18 (D18S535) short tandem repeat (STR) DNA polymorphisms. RESULTS: In all cases, candidate fetal NRBCs were accurately identified on the basis of morphologic and hemoglobin staining characteristics and confirmed to be fetal in origin based on the presence of shared and nonshared polymorphic DNA alleles when compared to DNA isolated from maternal cells. CONCLUSIONS: Using the erythroblast scoring system and subsequent analysis of inherited DNA polymorphisms, we were able to distinguish fetal NRBCs from maternal cells and prove fetal origin independent of gender. These results suggest that this novel combined approach to fetal cell isolation and genetic analysis is a promising method for noninvasive prenatal diagnostic applications.
Aneuploidy↗
Natural history of fetal cell microchimerism during and following murine pregnancy.
In humans, fetal cells enter the maternal circulation during all pregnancies and can persist for decades. Human studies, however, are often limited by the number of subjects and the availability of healthy and diseased tissues for analysis. We sought to develop a murine model to establish the natural history of fetal cell microchimerism in various maternal tissues during and after healthy pregnancies resulting from congenic and allogenic matings. We bred C57BL/6J and DBA/2J virgin female mice to C57BL/6J males transgenic for the enhanced green fluorescent protein (GFP), which shows autosomal dominant inheritance with complete penetrance and is under the control of a ubiquitous chicken beta-actin promoter and a cytomegalovirus enhancer. During pregnancy and at different times after delivery, female mice were sacrificed. Tissues were collected and the presence of the gfp transgene and GFP+ cells was assessed by real-time quantitative PCR and by immunofluorescence. During pregnancy, microchimerism was detected in all tissues from mice carrying GFP+ fetuses. Fetal cells were often mononuclear. The frequency of fetal cells in the lungs was significantly higher compared to other tissues. The level of microchimerism was also significantly higher in congenic compared to allogenic matings. After delivery, the frequency of fetal cells decreased and fetal cells were undetectable at 2 and 3 weeks after the first delivery. However, some mice that had three gestations had detectable fetal cells 3 weeks after their last delivery. Using sensitive methods of detection, we demonstrate that fetal cell microchimerism occurs during all murine pregnancies. We describe a useful model for the study of the consequences of this phenomenon.
Actins↗
Microchimerism: fears and hopes.
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Chimera↗
Fetal cell-free DNA circulates in the plasma of pregnant mice: relevance for animal models of fetomaternal trafficking.
BACKGROUND: Cell-free fetal DNA (fDNA) can be detected in maternal plasma throughout human pregnancy and is rapidly cleared after delivery. fDNA measurement has clinical application in many complications of pregnancy. Our aim was to determine if fDNA could be detected in maternal plasma during pregnancy in a mouse model system. We then compared the levels of fDNA during pregnancies in which the mother and fetus were either congenic or allogenic. METHODS: C57BL/6J (H-2b) or DBA/2J (H-2d) wild-type female mice were mated to C57BL/6J mice transgenic for the enhanced green fluorescent protein (gfp) and sacrificed while pregnant. C57BL/6J female mice that had previously given birth to three to six litters after mating with transgenic males were sacrificed after delivery. We used real-time quantitative PCR amplification to detect and measure gfp sequences in maternal plasma. RESULTS: fDNA was consistently detected in maternal plasma during pregnancy and was always absent after delivery [median 211 genome equivalents (GE)/ml vs 0 GE/ml, respectively, P=0.0001]. The level of fDNA was higher in allogenic matings compared to congenic matings (median 167 GE/ml/GFP + fetus vs 81 GE/ml/GFP + fetus, respectively). CONCLUSIONS: fDNA sequences can be reliably detected in maternal plasma during murine pregnancy. Our data lends further support to the use of nonhuman species to investigate the mechanisms involved in fetomaternal trafficking.
Animals↗
Transfer of fetal cells with multilineage potential to maternal tissue.
CONTEXT: During pregnancy, fetal CD34+ cells enter the maternal circulation, persist for decades, and create a state of physiologic microchimerism. Many studies have confirmed the residual presence of fetal cells in maternal blood and tissues following pregnancy. Fetal cells may respond to maternal injury by developing multilineage capacity in maternal organs. OBJECTIVE: To verify that fetal microchimeric cells express markers of epithelial, leukocyte, and hepatocyte differentiation within maternal organs. DESIGN, SETTING, AND PATIENTS: Archived paraffin-embedded tissue section specimens from 10 women who had male offspring and were previously found to have high numbers of microchimeric cells, and 11 control women who had no prior male pregnancies. Male cells were identified by fluorescence in situ hybridization, using X and Y chromosome-specific probes, followed by histologic and immunochemical studies using anticytokeratin (AE1/AE3) as a marker of epithelial cells, anti-CD45 as a leukocyte marker, and heppar-1 as a hepatocyte marker. MAIN OUTCOME MEASURE: Percentage of microchimeric cells expressing nonhematopoietic markers. RESULTS: A total of 701 male (XY+) microchimeric cells were identified (mean [SD], 227 [128] XY+ cells per million maternal cells). In maternal epithelial tissues (thyroid, cervix, intestine, and gallbladder), 14% to 60% of XY+ cells expressed cytokeratin. Conversely, in hematopoietic tissues, such as lymph nodes and spleen, 90% of XY+ cells expressed CD45. In 1 liver sample, 4% of XY+ cells expressed heppar-1. Histologic and immunochemical evidence of differentiation, as assessed by independent observers, was highly concordant (kappa = 0.72). CONCLUSION: The detection of microchimeric male cells, bearing epithelial, leukocyte, or hepatocyte markers, in a variety of maternal tissue specimens suggests the presence of fetal cells that may have multilineage capacity.
Adult↗
Clinical risk factors for mortality in patients with neurofibromatosis 1: a cohort study of 378 patients.
OBJECTIVE: To identify the main clinical features associated with mortality in patients with neurofibromatosis 1. DESIGN: Cohort study. SETTING: Referral center for neurofibromatosis. PATIENTS: Three hundred seventy-eight patients with neurofibromatosis 1 who had more than 1 year of follow-up in the center. MAIN OUTCOME MEASURES: Mortality. Clinical features, especially dermatological, were evaluated as potential factors associated with mortality. RESULTS: Factors associated independently with mortality were the presence of subcutaneous neurofibromas (odds ratio, 10.8; 95% confidence interval, 2.1-56.7; P<.001), the absence of cutaneous neurofibromas (odds ratio, 5.3; 95% confidence interval, 1.2-25.0; P =.03), and facial asymmetry (odds ratio, 11.4; 95% confidence interval, 2.6-50.2; P<.01). CONCLUSIONS: Some features that can be found by a routine clinical examination are associated with mortality in patients with neurofibromatosis 1. Clinical follow-up should be focused on patients with subcutaneous neurofibromas and/or the absence of cutaneous neurofibromas and/or facial asymmetry.
Adolescent↗
Quality of abstracts in 3 clinical dermatology journals.
BACKGROUND: Structured abstracts have been widely adopted in medical journals, with little demonstration of their superiority over unstructured abstracts. OBJECTIVES: To compare abstract quality among 3 clinical dermatology journals and to compare the quality of structured and unstructured abstracts within those journals. DESIGN AND DATA SOURCES: Abstracts of a random sample of clinical studies (case reports, case series, and reviews excluded) published in 2000 in the Archives of Dermatology, The British Journal of Dermatology, and the Journal of the American Academy of Dermatology were evaluated. Each abstract was rated by 2 independent investigators, using a 30-item quality scale divided into 8 categories (objective, design, setting, subjects, intervention, measurement of variables, results, and conclusions). Items applicable to the study and present in the main text of the article were rated as being present or absent from the abstract. A global quality score (range, 0-1) for each abstract was established by calculating the proportion of criteria among the eligible criteria that was rated as being present. A score was also calculated for each category. Interrater agreement was assessed with a kappa statistic. Mean +/- SD scores were compared among journals and between formats (structured vs unstructured) using analysis of variance. MAIN OUTCOME MEASURES: Mean quality scores of abstracts by journal and by format. RESULTS: Interrater agreement was good (kappa = 0.71). Mean +/- SD quality scores of abstracts were significantly different among journals (Archives of Dermatology, 0.78 +/- 0.07; The British Journal of Dermatology, 0.67 +/- 0.17; and Journal of the American Academy of Dermatology, 0.64 +/- 0.15; P =.045) and between formats (structured, 0.71 +/- 0.11; and unstructured, 0.56 +/- 0.18; P =.002). The setting category had the lowest scores. CONCLUSIONS: The quality of abstracts differed across the 3 tested journals. Unstructured abstracts were demonstrated to be of lower quality compared with structured abstracts and may account for the differences in quality scores among the journals. The structured format should be more widely adopted in dermatology journals.
Abstracting and Indexing↗
The influence of fetal loss on the presence of fetal cell microchimerism: a systematic review.
OBJECTIVE: Fetal cells enter the maternal circulation during most pregnancies. Their persistence for years occurs in only some women and has been associated with several autoimmune diseases such as systemic sclerosis. The objective of this study was to determine whether pregnancy history influences the persistence of fetal microchimeric cells. METHODS: We reviewed all reports of studies on fetal cell microchimerism, defined as male DNA in maternal tissue, that describe individual pregnancy histories, disease diagnoses, and microchimerism status. The total numbers of pregnancies, births, and sons, the history of fetal loss (spontaneous abortion and elective termination), and the presence of a maternal autoimmune disease were tested as factors potentially associated with persistent microchimerism. RESULTS: One hundred twenty-four subjects from 11 studies met the inclusion criteria. Only fetal loss was significantly associated with the presence of microchimerism (odds ratio 2.4, 95% confidence interval 1.2-6.0). CONCLUSION: These results suggest that fetomaternal cell trafficking following fetal loss may be important for the engraftment of microchimeric cells in maternal tissue. This may be due to an increased amount of fetomaternal transfusion or to transfer of a cell type that is more likely to engraft. We recommend that investigators in future studies on microchimerism report detailed pregnancy information, since these data are critical for the understanding of factors that influence the development of fetal cell microchimerism.
Adult↗
Cervical cancer and microchimerism.
OBJECTIVE: To determine whether microchimerism is involved in the pathogenesis or progression of cervical cancer. METHODS: Cervical tissue was obtained from eight women who had at least one live-born son and who underwent radical hysterectomy after a diagnosis of cervical cancer. Control tissue was obtained from four women without cervical cancer who had at least one live-born son and from three women with cervical cancer and no male births. Tissue sections were analyzed with fluorescence in situ hybridization for the presence of fetal cells, defined by an X and Y chromosome. Immunolabeling was used to determine the phenotype of the presumed fetal cells. RESULTS: Male cells were found in cervical tissue from all four patients for whom large sections (approximately 1.5 x 2 cm) were analyzed. Only one male cell was found in two of the four patients for whom small biopsy specimens (approximately 0.1 x 0.5 cm) were analyzed. No male cells were found in tissue specimens from controls, whether they were small or large sections. In immunolabeling studies, eight of 18 male cells from one patient were CD45-positive and nine of 37 male cells from two patients were cytokeratin-positive. No cells were positive for both markers. CONCLUSION: Cervical cancer might be associated with microchimerism, possibly from fetomaternal cell trafficking. These results further expand the potential relationship between microchimerism and disease in women.
Adult↗
Sneddon syndrome revealing dysfibrinogenemia.
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Adult↗
Medical management of neurofibromatosis 1: a cross-sectional study of 383 patients.
BACKGROUND: The morbidity and mortality caused by neurofibromatosis 1 are a result of complications that may involve any of the body systems. Two models of management have been proposed for the detection of various complications in specialized neurofibromatosis clinics: investigation protocols (including extensive imaging and analysis of 24-hour urinary catecholamine levels); or clinical follow-up without imaging. OBJECTIVE: Our purpose was to validate the strategy of clinical follow-up (without routine imaging and 24-hour urinary catecholamine levels). METHODS: We retrospectively compared the number of treated complications during 2 successive periods from our database: screening investigations from November 1988 to June 1995 and clinical examination from July 1995 to June 2000. RESULTS: The number of treated complications during the 2 periods was not statistically different (27/166 vs 28/217; Fisher's exact test, P =.39). CONCLUSION: Screening investigations added little to clinical follow-up. Indeed, routine clinical examination can easily identify complications that require treatment in adult patients with neurofibromatosis 1.
Adolescent↗
Fetal cell microchimerism: helpful or harmful to the parous woman?
PURPOSE OF REVIEW: Fetal cells enter the maternal circulation during most pregnancies and can persist in maternal blood and tissues after delivery. Concerns with regard to the histocompatibility of these fetal cells have raised the question of the long-term consequences of an immune response on maternal health. In the past few years, many investigators have demonstrated an association between the persistence of fetal cells in maternal tissues and blood and maternal autoimmune disease, especially systemic sclerosis. In this review we will summarize more recent data that provide a new insight into bi-directional feto-maternal cell trafficking. RECENT FINDINGS: Persisting fetal cells have been found in the tissue of women affected with endocrine or infectious disease as well as healthy parous women. SUMMARY: These data suggest the possibility that fetal microchimeric cells may also participate in the maternal physiological response to tissue injury. The medical consequences of pregnancy, therefore, appear to extend well beyond delivery.
Autoimmune Diseases↗
Combined FISH and immunolabeling on paraffin-embedded tissue sections for the study of microchimerism.
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Cell Nucleus↗