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[Malignant mesodermal mixed tumor of the bladder: report of a case].

A 59-year-old male took total cystourethrectomy on July, 1991, since the bladder tumor recurred 2 years and 4 months after transurethral resection. Six months after total cystourethrectomy, an abnormal mass shadow appeared on the right lower lung field. Metastatic lung tumor was strongly suspected from CT scan. Despite chemotherapy, the pulmonary lesion grew rapidly and the patient died. From the autopsy, metastatic lesions were found in the bilateral lung fields, skin (face, head and abdominal wall), pleura, bilateral kidneys, small intestine and lymph nodes (para-aortic and mesenteric). The primary bladder tumor contained histologically transitional cell carcinoma as the epithelial element and sarcomatous changes with osteoid formation as the non-epithelial elements. Thus, the primary lesion was diagnosed as a malignant mesodermal mixed tumor. However, all of the metastatic lesions showed only sarcomatous changes. Only 10 cases of malignant mesodermal mixed tumor of the bladder have been reported in Japan since Fujita's report. In general, total cystectomy is necessary for the treatment of this disease. It has a poor prognosis; 5 of the 10 patients died within one year after operation.

Humans↗

Extrauterine mixed mesodermal tumors. An immunohistochemical study.

Mixed mesodermal tumors are uncommon outside the uterus. Nine extrauterine mixed mesodermal tumors (eight ovarian and one extragenital) were selected for histochemical and immunoperoxidase study. In eight cases, both epithelial and mesenchymal elements were malignant (chondroid in six, rhabdomyoid in four, and osteoid in two). One ovarian tumor was an adenosarcoma. All cases were stained with periodic acid-Schiff with and without diastase and for alpha 1-antitrypsin, myoglobin, keratin, vimentin, muscle-specific actin, and alpha 1-antichymotrypsin, by using the avidin-biotin-immunoperoxidase method. The periodic acid-Schiff-positive, diastase-resistant droplets in several of the tumors showed peripheral alpha 1-antitrypsin positivity. Keratin delineated epithelial areas well in seven cases, and rhabdomyoid differentiation was confirmed with myoglobin in four cases. However, squamous elements in one tumor were falsely positive for myoglobin. We concluded that despite occasional cross-reactivity, carefully interpreted immunoperoxidase stains can be useful in distinguishing epithelial and mesenchymal elements in these tumors.

Female↗

A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein production.

A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein (AFP) production in a postmenopausal woman is reported, with special reference to its histogenesis. Judging from the serum AFP levels, the AFP content of the tumor and immunohistochemical localization of AFP in the tumor, AFP was produced by the tumor. The observation that in this patient AFP existed exclusively in carcinoma cells strongly supports the hypothesis that malignant transformation of Müllerian epithelial and stromal cells in mixed mesodermal tumors of the uterus occurs independently after the primitive mesenchymal cells have differentiated towards epithelial and stromal components.

Aged↗

Malignant mixed mesodermal tumour of the peritoneum with a complete response to cyclophosphamide.

We treated a 66-year-old Japanese woman with malignant mixed mesodermal tumour of the heterologous type arising from the paracolic peritoneum. The tumour contained heterologous elements in the form of cartilage in addition to carcinosarcomatous areas. This is the third case of malignant mixed mesodermal tumours originating from the peritoneum to be documented in the literature. A complete resection of the tumour was carried out but multiple lymph nodes metastases in the left neck occurred 5 months later. Cyclophosphamide in doses of 150 mg daily by mouth was initiated, with the result of a complete regression of the malignant lesions. She died of myocardial infarction 21 months after surgery.

Aged↗

[Malignant mesodermal mixed tumor of the ovary with neuro-ectodermic differentiation].

A striking ovarian tumour was observed in a post-menopausal, 54-year-old woman. Most of the tumour shows histologic features of a malignant mesodermal (müllerian) mixed tumour. However, this tumour harbours a peculiar component suggesting neuroectodermal neoplasia. Histochemical and immunohistochemical studies demonstrate focal pheochromocytomatous (or paraganglionic) and ganglionic differentiations. Several types of cells could be identified: ganglion cells (NSE +, neurofilaments +), pheochromocytes or paraganglion cells (chromogranin +), Schwann cells (S 100 protein +), and neuroblastomatous elements (NSE +). This neoplastic component could be compared with compound tumours such as pheochromocytomaganglioneuroblastoma or gangliocytic paraganglioma. This type of tumour has not been reported in ovary, notably in association with a mesodermal mixed tumour. Such observation prompts us to consider tumours of somatic origin containing germ cell-type elements, with a review of the literature.

Female↗

[Mixed mesodermal tumor of the uterine body].

During the 6-year period of 1976 to 1981, we studied 6 cases of mixed mesodermal tumor of the uterus. The incidence of occurrence of the tumor was 0.4% of all the gynecological inpatients, 1.4% of all the uterine malignancies, and 9.5% of the uterine body malignancies, and was higher than those reported by others. The patients were aged 49-75 years (mean 64 years), and 5 out of 6 patients were postmenopausal. Four patients had heterogeneous tumors (3 rhabdomyosarcomas and 1 chondrosarcoma). Two of the 6 patients are now living 34 and 14 months after treatment without clinical evidence of recurrence, respectively. Histologically, one of them showed only benign glandular structures as a component of epithelial elements, and the other one had no epithelial element. These findings suggest that the malignancy of the epithelial components may be one of the most important prognostic factors in the mixed mesodermal tumor of the uterus.

Aged↗

[Mesodermal (Muller) mixed ovarian tumor].

A case of mesodermal (Müller) mixed tumor of the ovary is described. The tumor consisted of the endometrial component with benign epithelial structures, stromal sarcoma, rhabdomyosarcoma, and elements of undifferentiated sarcoma. By its histological structure the tumor may be classified as one of the variants of mesodermal (Müller) mixed tumor of the heterologous adenosarcoma type.

Adult↗

Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes.

Wound healing is the response of tissue to injury that results in scar formation. Tissue regeneration would be a more ideal response. Previously, we have isolated a population of cells from avian, rodent, and rabbit skeletal muscle capable of differentiating into multiple mesodermal phenotypes. The present experiments were designed to determine whether a similar population of cells exist in human skeletal muscle. Separate cell preparations from skeletal muscle on an amputated leg of a 75-year-old female and the pectoralis muscle of a 27-year-old male were enzymatically dissociated and cultured to confluence in Eagle's minimal essential medium with 10 per cent preselected horse serum, then trypsinized, filtered, and slowly frozen in 7.5 per cent dimethylsulfoxide to -80 degrees C. The cells were thawed and plated with the same media plus dexamethasone (a nonspecific differentiation agent) at 10(-10) - 10(-6) M concentrations for up to 6 weeks. Immunological and histochemical staining assays were performed. Phenotypes observed included stem cells with typical stellate morphology (control), skeletal myotubes (anti-myosin), smooth muscle (anti-a-actin), bone (von Kossa stain), cartilage (Alcec blue), and fat (Sudan black B). These experiments establish the existence of a population of mesenchymal stem cells in human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. The possibility exists of manipulating the mesenchymal stem cells to achieve appropriate regeneration of mesenchymal tissues in the injured patient.

Adult↗

Stimulation of corneal wound healing with mesodermal growth factor.

Mesodermal growth factor (MGF) from mouse submaxillary glands was tested in vivo for stimulating effects on corneal wounds in rabbits. Intrastromal injection of 5 microgram of MGF induced widespread fibroblast activity and stromal cell division, and markedly stimulated stromal healing. At high doses (greater than 25 microgram), corneal destruction was indicated by extensive necrosis and perforation. When low doses (1 to 5 microgram) of MGF were applied to the lip of nonperforating knife wounds of the cornea, three major differences were noted between control and experimental wounds. In wounds treated with MGF, the depth of stromal healing was greater, as was the intensity of the fibroblast activity, and the width and depth of the epithelial plug were significantly decreased. These results establish that MGF is an effective growth-stimulating agent in vivo and that the initial stages of corneal wound healing may be accelerated in vivo.

Animals↗

Slug mRNA is expressed by specific mesodermal derivatives during rodent organogenesis.

We describe the expression pattern of the zinc-finger protein slug during rat and mouse embryonic development. Expression was mostly confined to migratory neural crest cells and several mesodermal derivatives. We could not detect slug expression in premigratory rodent neural crest cells, unlike previously studied vertebrates; the earliest substantial expression of slug was found in migratory cranial neural crest cells invading the first branchial arch. Their derivatives, comprising most of the craniofacial region, continued to express slug. Concomitantly, slug was expressed in sclerotome precursor cells prior to their separation from the differentiating somites. During organogenesis, slug was expressed in mesenchymal components of lung, digestive tract, meso- and metanephros until late stages. Slug was also found in mesenchymal cells undergoing cartilage and bone differentiation. Expression was down-regulated in parallel with chondrocyte phenotypic differentiation. Overall, slug appeared to be expressed by mesenchymal cells at predifferentiation stages involving cell migration and phenotype modulation. Expression was generally down-regulated afterwards. However, residual slug mRNA was found in several adult tissues, including liver and lung.

Animals↗

A cluster of Drosophila homeobox genes involved in mesoderm differentiation programs.

Although genes involved in common developmental programs are usually scattered throughout the metazoan genome, there are some important examples of functionally interconnected regulatory genes that display close physical linkage. In particular the homeotic genes, which determine the identities of body parts, are clustered in the Hox complexes and clustering is thought to be crucial for the proper execution of their developmental programs. Here we describe the organization and functional properties of a more recently identified cluster of six homeobox genes at 93DE on the third chromosome of Drosophila. These genes, which include tinman, bagpipe, ladybird early, ladybird late, C15, and slouch, all participate in mesodermal patterning and differentiation programs and show multiple regulatory interactions among each other. We propose that their clustering, through unknown mechanisms, is functionally significant and discuss the similarities and differences between the 93DE homeobox gene cluster and the Hox complexes.

Amino Acid Sequence↗

Novel FGF receptor (Z-FGFR4) is dynamically expressed in mesoderm and neurectoderm during early zebrafish embryogenesis.

We have identified a novel FGF receptor, Z-FGFR4, in zebrafish embryos. Z-FGFR4 is closely related to both chicken FREK (Marcelle et al. [1994] Development 120:683-694) and the Pleurodeles cDNA clone Pw-FGFR4 (also named PFR4). The Z-FGFR4 cDNA clones contain consensus sequences for two groups of two Ig-like domains, separated by eight acidic residues referred to as the "acid box." Z-FGFR4, therefore, is the first FGFR molecule yet described in vertebrates that contains four Ig domains in its amino-terminal region. Whole-mount in situ hybridization of staged zebrafish embryos, using probes prepared from a variety of domains of the Z-FGFR4 cDNA, reveal complex temporal and spatial expression patterns. Expression of Z-FGFR4 mRNA is first detected in embryos prior to gastrulation and then appears in prechordal plate mesendoderm. At this time, Z-FGFR mRNA is expressed in the epiblast in two distinct stripes which ultimately contribute to the brain. Eventually Z-FGFR4 transcripts are observed in forebrain, anterior hindbrain (rhombomeres 1, 3), and caudal hindbrain (rhombomere 7), as well as in the dorsal-most portion of the rostral spinal cord. Expression in axial mesendoderm appears transiently in notochord and segmental plate mesoderm. Eventually, Z-FGFR4 mRNA becomes restricted to the posterior somites and is absent in differentiated notochord. These detailed expression studies provide the basis for understanding FGFR function through an analysis, currently in progress, of the developmental consequences of Z-FGFR4 misexpression.

Animals↗

New case of axial mesodermal dysplasia sequence: epidemiologic evidence of a single entity.

We describe a child with manifestations of the oculo(facio)-auriculo-vertebral spectrum and caudal dysgenesis. This is the sixth axial mesodermal dysplasia sequence case to be reported. The infant was ascertained through the Spanish Collaborative Study of Congenital Malformations (ECEMC). It was possible to calculate the prevalence figure for the association of both conditions in the same child, as well as its expected chance frequency. Comparison of the expected with the observed frequency supports the suggestion that the concurrence of oculo(facio)-auriculo-vertebral sequence and caudal dysgenesis could well constitute a single entity.

Abnormalities, Multiple↗

Multiple herniae: a defect in the celomic mesoderm?

We report on a child with congenital bilateral cervical lung herniation with associated retrosternal (Morgagni), posterolateral (Bochdalek), esophageal hiatal, and inguinal herniae, and with multiple urinary bladder diverticuli. These multiple herniations may be secondary to a defect in the embryonic celomic mesoderm.

Consanguinity↗

Monoclonal antibodies identifying subsets of ectodermal, mesodermal, and endodermal cells in gastrulating and neurulating avian embryos.

The goal of our laboratory research is to elucidate the mechanisms underlying gastrulation and neurulation, using the avian embryo as a model system. In previous studies, we used two approaches to map the morphogenetic movements involved in these processes: (1) we constructed quail/chick transplantation chimeras in which grafted quail cells could be identified within chick host embryos by the presence of nucleolar-associated heterochromatin, and (2) we microinjected exogenous cell markers. However, it would be advantageous to be able to detect endogenous markers to demarcate various subsets of cells within the unmanipulated embryo. To elucidate such a series of natural markers, we have used monoclonal antibodies to identify epitopes found on subsets of ectodermal, mesodermal, and endodermal cells. Antibodies were made by immunizing mice against either homogenized ectoderm (i.e., prospective neural plate and surface ectoderm) or primitive streak, which had been microdissected from stage 3 chick embryos. Additionally, we screened a panel of antibodies made against soluble protein obtained from isolates of cell nuclei from late embryonic chick brain. Here, we describe the labeling patterns of three monoclonal antibodies, called MAb-GL1, GL2, and GL3 (GL, germ layer), during avian gastrulation and neurulation. Our results show that labeling early avian embryos with monoclonal antibodies can reveal previously undetected distributions of cells bearing shared epitopes, providing new labels for subsets of cells in each of the three primary germ layers.

Animals↗

Regulation of Epha4 expression in paraxial and lateral plate mesoderm by ectoderm-derived signals.

Somitogenesis in all vertebrates involves a mesenchymal to epithelial transition of segmental plate cells. Such a transition involves cells altering their morphology and their adhesive properties. The Eph family of receptor tyrosine kinases has been postulated to regulate cytoskeletal organization. In this study, we show that a receptor belonging to this family, EphA4, is expressed in the segmental plate in a region where cells are undergoing changes in cell shape as a prelude to epithelialization. We have identified the ectoderm covering the somites and the midline ectoderm as sources of signals capable of inducing EphA4. Loss of EphA4 results in cells of irregular morphology and somites fail to form. We also show that when somites fail to develop, expression of EphA4 in the lateral plate is also lost. We suggest that signaling occurs between the somites and the lateral plate mesoderm and provide evidence that retinoic acid is involved in this communication.

Animals↗

Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites.

The paired box containing transcription factor Pax3 is a crucial regulator of dermomyotome and muscle development. However, the allelic series of Pax3/Splotch mutants also displays characteristic vertebral column malformations, which do not result from defective dorsoventral somite pattern. Rather, vertebral column and sclerotomal phenotypes are reminiscent of the phenotypes observed in the segmentation/somitogenesis mutants rachiterata and pudgy. Moreover, rostrocaudal somite pattern and somitic boundaries are disturbed in Splotch as monitored by the expression of Uncx4.1 and Lunatic fringe. Alterations in EphA4, Dll1, and Uncx4.1 expression are evident already in the condensing paraxial mesoderm, correlating with the first phase of Pax3 expression before and during somite formation. This finding suggests an early function of Pax3 during the formation of epithelial somites.

Animals↗