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PubMed2002

Cell coherence during production of the presomitic mesoderm and somitogenesis in the mouse embryo.

In this study, we investigated (in the early mouse embryo) the clonal properties of precursor cells which contribute to the segmented myotome, a structure derived from the somites. We used the laacZ method of single cell-labelling to visualise clones born before segmentation and bilateralisation. We found that clones which contribute to several segments both unilateral and bilateral were regionalised along the mediolateral axis and that their mediolateral position was maintained in successive adjacent segments. Furthermore, clones contributed to all segments, from their most anterior to their most posterior borders. Therefore, it appears that mediolateral regionalisation of myotomal precursor cells is a property established before bilateralisation of the presomitic mesoderm and that coherent clonal growth accompanies cell dispersion along both the mediolateral and anteroposterior axes. These findings in the mouse correlate well with what is known in the chick, suggesting conservation of the mode of production and distribution of the cells of the presomitic mesoderm. However, in addition, we also found that the mediolateral contribution of a clone is already determined in the pool of self-renewing cells that produces the myotomal precursor cells and thus that this pool is itself regionalised. Finally, we found that bilateral clones exhibit symmetry in right and left sides in the embryo at all levels of the mediolateral axis of the myotome. All these properties indicate synchrony and symmetry of formation of the presomitic mesoderm on both sides of the embryo leading to formation of a static embryonic structure with few cell movements. We suggest that sequential production of groups of cells with an identical clonal origin for both sides of the embryo from a single pool of self-renewing cells, coupled with acquisition of static cell behaviour, could play a role in colinearity of expression of Hox genes and in the segmentation system of higher vertebrates.

Animals↗
PubMed1992

Mixed mesodermal tumor of the ovary: analysis of prognostic factors in 31 cases.

OBJECTIVE: To determine significant prognostic factors in patients with mixed mesodermal tumors of the ovary. METHODS: Thirty-one cases of mixed mesodermal tumor of the ovary treated at Memorial Sloan-Kettering Cancer Center between 1977-1990 were reviewed retrospectively. The mean patient age was 61 years. Distribution by stage was as follows: I, seven (23%); II, one (3%); III, 15 (48%); and IV, eight (26%). The median follow-up for survivors was 62 months. Following primary surgery, chemotherapy included cisplatin (four), doxorubicin (seven), or both (ten); six patients received various other treatments. RESULTS: The median survival for the entire group was 10.6 months. In 19 cases (61%), heterologous sarcomatous elements were present in the primary tumor, whereas 12 (39%) contained homologous elements only. There was a trend toward improved survival in patients whose primary tumors had only homologous stromal elements (P = .06). The overall survival was significantly better for the eight patients with early-stage (I, II) disease than for the 23 patients with advanced-stage (III, IV) disease (P = .01). The size of residual disease after cytoreductive surgery was not a significant prognostic factor. There was no difference in survival between the ten women whose metastatic disease contained only epithelial elements and the 16 whose metastases contained mesenchymal elements as well (P = .23). CONCLUSIONS: This study confirms previous observations that mixed mesodermal tumors of the ovary are a highly malignant group of tumors that respond poorly to chemotherapy. In addition, we demonstrated that prognosis is independent of the presence or absence of sarcomatous elements in the metastases.

Aged↗
PubMedDate not supplied

[Mixed mesodermal tumors of the uterus. Clinico-pathologic characteristics of 23 patients].

The clinical and pathological features, histogenesis and treatment of 23 cases of mixed mesodermal tumours of the uterus (15 benign and 8 malignant) in woman aged from 27 to 78 years (mean 51.25) are reviewed. The tumours manifested by non-specific symptoms, most often uterine bleeding, arising suspicion of malignancy in only two cases. Unlike malignant mixed mesodermal tumours, differentiation of adenofibromas from low-grade adenosarcomas was often very difficult, and needed careful pathohistological analysis of extirpated tissues, including all available histochemical, immunohistochemical and EM procedures. Two cases of adenofibromas recurred as adenosarcomas after four months and five years respectively. Poor prognosis of malignant variants of mixed mesodermal tumours and their difficult differentiation from adenofibromas require close collaboration of pathologists and gynaecologists, implicating hysterectomy as proposed treatment and permanent clinical monitoring.

Adult↗
PubMed1986

Phase II trial of cisplatin in the treatment of patients with advanced or recurrent mixed mesodermal sarcomas of the uterus: a Gynecologic Oncology Group Study.

Thirty-four patients with advanced or recurrent mixed mesodermal sarcoma of the uterus were entered in a study of single-agent cisplatin as second-line chemotherapy at a dose of 50 mg/m2 iv every 3 weeks. Twenty-eight of the 34 patients had mixed mesodermal sarcomas and measurable disease and had received one or more courses of the drug. Of these patients, five (18%) had objective response to therapy. Two patients who developed clinical complete response had long progression-free intervals (14 and 16 months) and remained alive at 21 and 36 months after initiation of therapy. Adverse effects were those described in a number of series employing cisplatin and were tolerable. Cisplatin thus appears to have definite activity as a second-line agent in the treatment of mixed mesodermal sarcomas of the uterus.

Cisplatin↗
PubMed1984

Establishment and characterization of two human mixed mesodermal tumor cell lines from the same patient.

A cell line designated HIRS -BM was established from fluid aspirated from the sternal bone marrow of a 16-year-old female. Another cell line ( HIRS -PB) was derived from the peripheral blood of the same patient. Both lines grew well, multilayering rapidly without contact inhibition, and 62 serial passages were successively done within 28 months. Both cultures contained spindle- or fibrous-shaped cells that revealed neoplastic and pleomorphic features, and these cells were characterized as possessing cross-striations in the cytoplasm. The cross-striations were detected by phosphotungstic acid hematoxylin stain. Some elongated cells were stained positively with anti-myoglobin by use of periodic acid-Schiff methods. The primary tumor in the uterus was diagnosed as a mixed mesodermal tumor composed of adenocarcinoma and rhabdomyosarcoma cells. The karyotype exhibited hyperploidy and large submetacentric marker chromosomes, and the modal chromosome number was 84. No difference was found between the 2 cell lines except for growth behavior and heterotransplantability . HIRS -BM cells grew more rapidly and were highly transplantable. The HIRS -BM cells were transplanted into the subcutis of BALB/c nude mice and produced mixed mesodermal tumors resembling the uterine tumor, while the HIRS -PB cells could not be transplanted. Due to the histogenesis of the mixed mesodermal tumor being's obscure with histologic observations only, this study was performed to obtain data by tissue culture of the tumor and resulted in support of the combination theory reported in the literature in regard to tumor.

Adolescent↗
PubMed1982

[Development of the adenylate cyclase activity of the embryonic chorda-mesoderm and endoderm during the migration of primordial germ cells in Xenopus laevis (anuran amphibian)].

In the embryo of Xenopus laevis, adenylate cyclase activity is higher in the chorda-mesoderm than in the endoderm. The peak of activity in the chorda-mesoderm is observed at the beginning of the migration of the primordial germ cells (PGC). There could be a correlation between the adenylate cyclase activity of the chorda-mesoderm and the intraendodermic migration of the PGC.

Adenylyl Cyclases↗
PubMed1994

[Heterologous mesodermal adenosarcoma of the endocervix. Description of a clinical case].

We describe a case of an endocervical heterologous mesodermal adenosarcoma, found in a 43 year old woman. Among mesodermal neoplasms, various histological types are distinguished: the carcinosarcoma, the embryonal rhabdomyosarcoma or botryoid sarcoma, and the adenosarcoma; the last is formed by a benign epithelial component and by a malignant stromal component, that may contain heterologous tissues, such as cartilage, skeletal muscle, etc. Adenosarcoma is a tumor of the uterine corpus and seems to be most common among menopausal women. A primitive adenosarcoma of the uterine cervix is very rare; in fact the overall percentage of the uterine cervical sarcoma is 0.2-0.4%. The patient, age 43 years, with regular menstrual bleeding came to an outpatient clinic referring a post coital metrorrhagia. After a control examination, a polyp from the uterine cervix was removed; the histopathologic diagnosis was: fibroangioadenomatous polyp of the isthmus with cartilaginous metaplastic areas. Two months later, the patient was referred to our clinic and another cervical polyp was removed. The histological diagnosis was adenosarcoma with chondrosarcomatous heterologous mesodermal component. Then the patient was operated and the postoperative histological examination confirmed the preoperative diagnosis. A literature review about the uterine adenosarcoma etiopathogenesis is reported, and a suitable diagnostic iter, is discussed.

Adenosarcoma↗
PubMed1997

Structure and cytoskeletal organization of migratory mesoderm cells from the Xenopus gastrula.

Prospective mesoderm cells from the Xenopus gastrula exhibit interesting motile behavior, e.g., a transition from a nonmigratory state to an active translocation that can be induced experimentally, and directional substrate-guided locomotion. We examine the cytoskeletal organization of these embryonic cells. We show that the large, globular cells are enclosed in a triple shell consisting of an actomyosin cortex, a peripheral cytokeratin layer, and a peculiar microtubule basket that surrounds the cell body and constrains the distribution of large inclusions such as yolk platelets. Consistent with the migratory phenotype of these cells, no stress fibers or focal contacts are present. Mesoderm cells possess typical lamellipodia with fine protruding filopodia. The leading edge of the lamellar part exposes binding sites for the fodrin SH3 domain. Lamellipodia are connected to the cell body through actin filament bundles of the upper cell cortex. Myosin II is present in the cell body and extends to varying degrees into lamellipodia. We present indirect evidence that myosin II is located in the upper part of lamellipodia and propose a model that involves myosin II in a dynamic linkage between lamellipodium and the cortex of the cell body.

Actins↗
PubMed1996

Mesoderm-specific expression of the divergent homeobox gene Hlx during murine embryogenesis.

We have determined the expression pattern of the divergent homeobox gene Hlx during post-implantation mouse development, utilizing in situ hybridization. Expression was mesoderm-specific and occurred in a complex tissue distribution. Transcripts were first detected at 9.5 days post coitum (p.c.) in splanchnic mesoderm of the midgut and hindgut region, then during organogenesis, prominently in mesenchyme of the developing liver, gall bladder, and intestines, as well as their mesenteric tissues. In the foregut, lung mesenchyme became positive from 10.5 days p.c. Hlx transcripts were also detected in a subset of skeletal myogenic cells: those within branchial arches from 9.5 days p.c. and within limb buds from 12 days p.c. Hlx was not expressed in myogenic cells which are derived from the myotome and populate the trunk. However, from 10 days p.c., expression was seen in a region of the sclerotome immediately adjacent to the myotome and corresponding to precursors of the ribs and vertebral neural arches. In the anterior-posterior aspect of the developing sclerotome, Hlx expression was out of register with original segmental boundaries (intersomitic fissures), a pattern consistent with a classical hypothesis that the developing vertebral column undergoes resegmentation. Hlx expression was also observed in vibrissae, pericardium, snout mesenchyme, and meningeal epithelium. Overall, expression of Hlx in only a subset of individual lineage progenitors and at know sites of inductive tissue interactions, suggests that the gene regulates local patterning or growth through cell:cell signalling at those embryonic sites.

Animals↗
PubMed1996

Mesodermal development in mouse embryos mutant for fibronectin.

Three independent mutations were made by homologous recombination in two different regions of the fibronectin (FN) gene; all three appeared to be functional null mutations. The embryonic lethal phenotypes of these mutations were indistinguishable; all three FN mutant strains show mesodermal defects and fail to develop notochord or somites. Nevertheless analysis with lineage markers (Brachyury, sonic hedgehog, Notch-1, and mox-1) showed that both the notochord and the somite lineages were induced at the correct times and places. Furthermore, notochord precursor cells showed extensive cell migration in the absence of FN. However, neither notochord nor somites condensed properly in the absence of FN. These results show that specification of notochordal and somitic mesodermal lineages and significant cell migration are independent of fibronectin but that correct morphogenesis of these structures is FN-dependent.

Animals↗
PubMed1997

Morphogenetic potential of the chick leg interdigital mesoderm when diverted from the cell death program.

There is evidence that the interdigital mesoderm may be in an undifferentiated state. For example, under experimental manipulation in vivo it may be diverted from cell death to digit formation. In the present work we wanted to analyze the maximum morphogenetic potential of the interdigital cells. To do this we made recombinant limbs of three types, the first using dissociated-reaggregated leg interdigital mesoderm, the second using the same tissue but without dissociation and the third adding a piece of polarizing region to the dissociated interdigit. In all three the massive cell death of the interdigit failed to occur. The first type of recombinant formed a small nodule of cartilage while the other two formed a well-developed digit. Our data indicate that the maximum morphogenetic potential of the interdigital tissue appears constrained to form digits and that dissociation of the tissue decreased this ability; polarizing region restores the ability of dissociated cell recombinants to form a digit. We also analyzed in these recombinants the expression of a battery of genes implicated in interdigital cell death or in digital morphogenesis. The pattern of expression of each gene analyzed was identical in the three types of recombinant limbs. The expression of Msx1 and Msx2 genes was maintained under the ridge indicating a good interaction between the interdigital cells, both dissociated and undissociated, and the apical ridge. The expression of Hoxd-12, Hoxd-13 and Hoxa-13 genes was maintained in the recombinants, indicating that these cells carry information about their autopodial origin, and this correlates well with their distal restricted morphogenetic potential. Finally, the patterns of expression of the Bmp-2, Bmp-4 and Bmp-7 genes indicated that they are independently regulated in the recombinants and that Bmp-4 and Bmp-7 have wider expression domains than the areas of cell death that were only detected under the regressing apical ridge during day 3 of the experiment.

Animals↗
PubMed1999

Ectopic expression of the transforming growth factor beta type II receptor disrupts mesoderm organisation during mouse gastrulation.

Transforming growth factor beta (TGFbeta) regulates the cell cycle and extracellular matrix (ECM) deposition of many cells in vitro. We have analysed chimaeric mouse embryos generated from embryonic stem cells with abnormal receptor expression to study the effect of TGFbeta on these processes in vivo and the consequences for normal development. The binding receptor for TGFbeta, TbetaRII, is first detected in the embryo proper around day 8.5 in the heart. Ectopic expression of TbetaRII from the blastocyst stage onward resulted in an embryonic lethal around 9.5 dpc. Analysis of earlier stages revealed that the primitive streak of TbetaRII chimaeras failed to elongate. Furthermore, although cells passed through the streak and initially formed mesoderm, they tended to accumulate within the streak. These defects temporally and spatially paralleled the expression of the TGFbeta type I receptor, which is first expressed in the node and primitive streak. We present evidence that classical TGFbeta-induced growth inhibition was probably the cause of insufficient mesoderm being available for paraxial and axial structures. The results demonstrate that (1) TGFbeta mRNA and protein detected previously in early postimplantation embryos is present as a biologically active ligand; and (2) assuming that ectopic expression of TbetaRII results in no other changes in ES cells, the absence of TbetaRII is the principle reason why the embryo proper is unresponsive to TGFbeta ligand until after gastrulation.

Animals↗
PubMed1986

An association of caudal malformations arising from a defect in the "axial mesoderm" developmental field.

We have studied two newborn infants with a remarkable genital malformation, failure of urethral development with enormous bladder distension, atresia of the distal hindgut, vertebral abnormalities, and compression deformities. This is a pattern of anomalies similar to, and probably an extension of, the association of female pseudohermaphroditism and other anomalies (FPA) described by Lubinsky [Am J Med Genet 6:123-136, 1980]. We propose that its pathogenesis involves a defect expressed in mesoderm, especially caudal mesoderm. We offer some speculation on what might be its nature, with particular reference to the theory of cell surface molecules having a role in morphogenesis. We apply the concept of the developmental field to provide a clarifying perspective.

Abnormalities, Multiple↗
PubMed1992

Chromosome analysis in spontaneous pregnancy loss: use of placental villus mesodermal core cell cultures.

Culture of placental villus mesodermal core cells, a method developed for chorionic villus sampling, was used for cytogenetic analysis in 168 spontaneous pregnancy losses. Successful karyotype results were obtained in 72% of cases and 87.5% of cases in which placental tissue was available. Culture of placental villus mesodermal core cells is useful in the evaluation of spontaneous pregnancy loss, particularly when tissues of direct fetal origin are unavailable or unsuitable for culture. Details of culture and specimen handling techniques are provided.

Abortion, Spontaneous↗
PubMed1993

Axial mesodermal dysplasia spectrum.

We report on a 4-month-old boy with manifestations of both the oculo-auriculovertebral spectrum and the caudal regression sequence. He has preauricular appendages, thoracic and lumbar hemivertebrae, anomalies of the ribs, dextrocardia, sacral "dysplasia," dislocated hips, bilateral talipes equinovarus, imperforate anus, recto-vesical fistula, malformed scrotum, and undescended testes. As suggested by Russell et al. [1981], who reported a patient with similar anomalies, the spectrum of anomalies probably is due to a generalized alteration in mesodermal cell migration during the primitive streak period. The term "axial mesodermal dysplasia spectrum" best describes the widespread anomalies in the cranial and caudal regions.

Abnormalities, Multiple↗
PubMed1994

Lower mesodermal defects: a common cause of fetal and early neonatal death.

Among the first 1,130 referrals to the Wisconsin Stillbirth Service Program 17 infants have been recognized to share phenotypic characteristics involving the genital, urinary, lower gastrointestinal, and axial skeletal systems. The pattern of abnormalities identified appears to be limited to structures sharing a common embryologic origin. These features, for the most part, are shown to be non-randomly associated. No clearly definable sub-groups within this population are demonstrable. The pattern of abnormalities is defined to include abnormalities of the following structures as pathogenetically primary features: lumbosacral vertebrae, kidneys, ureters, uterus/fallopian tubes, vagina, bladder, urethra, adrenals, gonads, anorectum, external genitalia, and umbilical arteries. An embryologic mechanism is proposed which explains this non-random association as arising secondary to disruption of structures derived from the lower portion of the primitive intraembryonic mesoderm. The Lower Mesodermal Defects Sequence appears to be a rather common (and under-recognized) cause of stillbirth and immediate neonatal death.

Adrenal Glands↗
PubMed2003

Overlap between VACTERL and hemifacial microsomia illustrating a spectrum of malformations seen in axial mesodermal dysplasia complex (AMDC).

We describe a male infant born to consanguineous healthy parents with multiple congenital anomalies of the skeleton and internal organs. His phenotype displays an overlap between VACTERL and hemifacial microsomia (oculo-auriculo-vertebral spectrum/OAV). In addition, striking asymmetry of the malformations further supports the classification as part of the "axial mesodermal dysplasia complex" (AMDC) which is supposed to arise from disturbed mesodermal cell migration during early blastogenesis. The present case was instructive to review the continuous spectrum of AMDC related anomalies.

Abnormalities, Multiple↗