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[Reciprocal homology of the preotic mesodermal segments of representatives of different classes of vertebrates].

The data of the literature and those of the author on the origin of preotic mesodermal segments are discussed. Only in Cyclostomata all preotic segments are formed from the wall of archenteron and are larval segments. In all the gnathos tomata, the primary gastral segments are substituted, to different degrees, by postlarval peristonal mesoderm. The preotic mesomeres of Cyclostomata are homologous to II--IV mesomeres of Branchiostoma lanceolata. The anterior cephalic cavity and the premandibular segment of the elasmobranchia are homologous to I and II segments of Branchiostoma lanceolata. The mandibular mesoderm of the elasmobranchia includes the gastral mesoderm (homologous to III and some subsequent segments of Brachiostoma lanceolata) and peristomal mesoderm. The mandibular mesoderm in higher vertebrates has the same composition, but their anterior larval segments disappear and are substituted by gastral part of the mandibular mesoderm.

Amphibians

Mixed mesodermal tumor of the uterine body: relationship between histology and survival.

A clinico-pathological study of 20 cases of mixed mesodermal tumor of the uterine body is reported. Fifteen tumors were found after menopause. The mean age of all cases was 55.5 years. Histologically, mixed mesodermal tumors consisted of two different components; epithelial and sarcomatous patterns, in 18 cases. Mixed mesodermal tumors in four of the 18 cases had no adenocarcinomatous elements but showed a benign glandular structure. In the remaining two tumors, epithelial patterns were absent and only heterologous sarcomatous elements were found. Ten of the patients had received hysterectomy more than five years ago. Three of these patients, having no malignant but benign epithelial component, showed a relatively good prognosis. Adenocarcinomatous elements were found in six cases, and four patients with carcinomatous elements had poor prognosis. It can be stated that the prognosis of mixed mesodermal tumor chiefly depends on the malignancy of epithelial components, when comparing the prognosis of the tumors at the same clinical stage. On the other hand, sarcomatous elements are not likely to reflect the prognosis of the tumors. Mixed mesodermal tumor is monodermal in origin, namely, mesodermal origin, and might arise from the Muellerian duct or more primitive mesodermal tissue.

Adult

Effects of cytosine arabinoside, 6-aminonicotinamide, and 6-mercaptopurine riboside on ectoderm and mesoderm of mouse limb buds.

The effects of cytosine arabinoside, 6-aminonicotinamide, and 6-mercaptopurine riboside on the incorporation of [14C] glucose moieties and [32P] phosphate into acid-soluble material and lipids, RNA, DNA, and protein were measured in the dissected mesoderm and ectoderm of mouse limb buds at the 42-45 (day 11) somite stage. Due to the different proliferative capacities of the two tissues the incorporation of the precursors into mesodermal cells was considerably higher the than into ectodermal ones. Cytosine arabinoside inhibited the incorporation of the precursor moieties only into DNA, but very early after its application. This effect was more obvious in mesoderm than ectoderm. 6-Aminonicotinamide interfered only with glucose metabolism, whereas the incorporation of phosphate was not affected. 14C radioactivity in the various cell components was similarly reduced in mesoderm and ectoderm. 6-mercaptopurine riboside caused an increased incorporation of precursor material in all fractions studied in the mesoderm as well as in the ectoderm during the first 12 hours. This was succeeded by a dramatic decrease of incorporated 14C and 32P radioactivity. Differences of response in the tissues could not be detected with this drug. It is suggested that the malformations of the extrmities caused by these antimetabolites may be predominantly attributed to changes in the cell function rather than to gross effects on cell metabolism.

6-Aminonicotinamide

Changes at the ecto-mesodermal interface during development of the duck preen gland.

An ultrastructural investigation of the organogenesis of the duck preen gland showed variations at the ecto-mesodermal interface in the course of development. During the period of invagination, ectoderm and mesoderm were separated by a continuous basal lamina. Morphogenesis of the tubules is characterized by a preferential deposition of non-oriented collagen fibres localized at the branching sites. Direct contacts between ectodermal extensions and mesodermal cells, through gaps in the basal lamina, appeared at the end-buds after the morphogenetic pattern was established and before the onset of the glandular secretory activity. The correlation between the modification of the ecto-mesodermal interface and the differentiation of uropygial ectoderm is discussed.

Animals

Interrelationship between poly (ADP-Rib) synthesis, intracellular NAD levels, and muscle or cartilage differentiation from mesodermal cells of embryonic chick limb.

Mesodermal cells of embryonic chick limbs have the capacity to differentiate into either muscle or cartilage. Previous reports from this laboratory show a correlation between pyridine nucleotide levels and this differentiation, and thus suggest that fluctuations in the cellular NAD levels play a role in the control of muscle versus cartilage development. Poly(ADP-Rib) is chromatin-associated and forms from the polymerization of NAD with the excision of nicotinamide. The studies reported here show that: (A) the rate of net synthesis of poly(ADP-Rib) is correlated with the differentiation of chondrogenic cells from stage 24 limb mesodermal cells grown in vitro; (B) inhibition of chondrogenic expression caused by exposure to nicotinamide or BrdUrd is correlated with maintenance of basal levels of poly(ADP-Rib) synthesis, and this inhibition is dependent on the concentration of nicotinamide or BrdUrd exogenously supplied; (C) potentiation of chondrogenic expression caused by exposure of limb mesodermal cells in vitro to 3-acetylpyridine is correlated with stimulation of the rate of poly(ADP-Rib) synthesis if corrected for the specific activity of the ATP pool or compared to untreated cultures on a per cell basis; (D) isolated chromatin from mesodermal cells has the enzymatic machinery for synthesizing poly(ADP-Rib); (E) this machinery is inhibited by nicotinamide, thymidine, and 3-acetylpyridine; and (F) newly synthesized poly(ADP-Rib) is either associated with a discrete fraction of chromatin or is completely extracted from chromatin by the high column salts, which result in an aggregation with eventual elution at the exclusion volume position of the agarose column. Taken together, these observations provide a possible explanation for how fluctuations in cellular NAD levels can communicate with or be "sensed" by genomic related machinery and eventually result in differtial phenotypic expression.

Adenine

Origin and differentiation of the yolk sac and extraembryonic mesoderm in presomite human and rhesus monkey embryos.

Reexamination of presomite human and rhesus monkey embryos in the Carnegie Collection provides no evidence to corroborate the hypothesis that the trophoblast is the source of all extraembryonic tissues in these embryos. Instead, the present study indicates that the developmental pattern of the yolk sac and extraembryonic mesoderm is homologous to that in other eutharian mammals. The primary yolk sac of 10- to 11-day human blastocysts is partially filled with a meshwork of extraembryonic endoderm, whereas such a meshwork is absent in the rhesus monkey. It is suggested that this endodermal meshwork develops as the result of interstitial implantation in the human embryo. A small secondary yolk sac develops in 12- to 13-day human and macaque embryos as the result of pinching off of a portion of the larger primary yolk sac. Development of a secondary yolk sac in higher primates appears to be related causally to differential rates of expansion of the blastocyst and primary yolk sac within the simplex uterus. The caudal margin of the primitive streak develops precociously in 12- to 14-day human and macaque embryos, and this appears to be the source of all the extraembryonic mesoderm of the chorion, chorionic villi, and body stalk. It is suggested that the peripheral spread of extraembryonic mesoderm plays in inductive role in the development of chorionic villi, similar to other types of epithelial-mesenchymal inductive interactions. In contrast to previous hypotheses, the human and macaque trophoblasts appear to give rise only to additional trophoblast.

Amnion

Cyclic AMP derivatives stimulate the chondrogenic differentiation of the mesoderm subjacent to the apical ectodermal ridge of the chick limb bud.

Recent studies indicate that one of the major functions of the apical ectodermal ridge (AER) of the embryonic chick limb bud is to maintain mesenchymal cells directly subjacent to it (i.e., cells extending 0.4-0.5 mm from the AER) in a labile, undifferentiated condition. Furthermore, when mesenchymal cells are freed from the AER's influence, either artifically or as a result of normal polarized proximal-to-distal limb outgrowth, they are freed to commence cytodifferentiation. In a preliminary attempt to investigate at a molecular level the mechanism by which the AER exerts its "negative" effect on the cytodifferentiation of subridge mesenchymal cells, we have examined the effect of a variety of agents that elevate cyclic AMP levels on the chondrogenic differentiation of the unspecialized subridge mesoderm of the limb bud in an organ culture system. Dibutyryl- and 8-hydroxy-cyclic AMP elicit a dose-dependent increase in the rate and amount of cartilage matrix formation and a corresponding dose-dependent increase in sulfated glycosaminoglycan accumulation by subridge mesoderm explants. The stimulatory effect of suboptimal concentrations of cyclic AMP derivatives is potentiated by the addition of theophylline. The stimulatory effect is limited to cyclic AMP derivatives, since dibutyryl-cyclic GMP and 5'-AMP have no effect. Thus agents that elevate intracellular cyclic AMP levels stimulate the chondrogenic differentiation of the unspecialized subridge mesoderm of the embryonic chick limb bud.

Animals

Carcinosarcomas and mixed mesodermal tumors of the ovary: a clinicopathologic study of six cases.

A clinicopathologic study of three ovarian carcinosarcomas and three mixed mesodermal tumors of the ovary is presented. None of the patients survived for more than 1 year, irrespective of chemotherapeutic treatment or the extent of surgery. No prognostic differences were noted between the histologic patterns of varying tumor sizes of carcinosarcomas and mixed mesodermal tumors. The association of these two entities with other neoplasms of Müllerian nature suggests a multicentric tumor response of Müllerian tract derivatives. The necessity of adequate sampling, both for correct diagnosis and to exclude the possibility of teratoma (which behaves in a more benign fashion), is emphasized.

Aged

Mixed mesodermal tumor and clear cell carcinoma arising in ovarian endometriosis.

A case is reported of clear cell carcinoma, arising as several papillary masses from the lining of an endometrial cyst within the ovary, associated with a mixed mesodermal tumor arising in the stalk of the largest papillary nodule. The origin of this tumor from within a focus of endometriosis lends support to the theory that both the epithelial and mesodermal components are of Müllerian (Paramesonephric) origin.

Adenocarcinoma

Extrauterine mesodermal (müllerian) adenosarcoma: a clinicopathologic analysis of five cases.

Five extrauterine examples (three pelvic and two ovarian) of a distinctive mesodermal (müllerian) mixed tumor previously described to occur in the uterus and designated müllerian adenosarcoma are reported. The tumors were diagnosed during the fifth to eight decades of life. They usually formed very large, partly cystic masses, which had occasionally spread to adjacent organs by the time of operation. On microscopic examination the tumors consisted of benign-appearing neoplastic glands lying in a sarcomatous stroma. The glands were lined by a variety of müllerian epithelial cell types, and the stromal element resembled endometrial stromal sarcoma. Three patients had malignant courses manifested by intrabdominal recurrence, distant metastases, or both. This tumor should be clearly distinguished from the more common forms of mesodermal (müllerian) mixed tumor in which the epithilial as well as the stromal component is malignant and the prognosis is much more grave.

Adult

Ultrastructure of mesodermal mixed tumor of the uterus.

A case of mesodermal mixed tumor arising in the uterus of a 57-year-old woman is presented. The tumor was a mixture of adenocarcinoma with occasional squamous metaplasia, stromal sarcoma, myxosarcoma and chondrosarcoma. Light and electron microscopic examinations of the tumor revealed close transition between stromal sarcomatous component and each of other sarcomatous and carcinomatous component. The histogenesis of mixed mesodermal tumor was discussed and it was concluded that the tumor might be derived from endometrial stromal cell which possessed the pluripotency to differentiate toward various epithelial and mesenchymal tissues including the heterologous mesenchymal tissue.

Adenocarcinoma

Immunological and biochemical studies of collagen type transition during in vitro chrondrogenesis of chick limb mesodermal cells.

This work describes an approach to monitor chondrogenesis of stage-24 chick limb mesodermal cells in vitro by analyzing the onset of type II collagen synthesis with carboxymethyl-cellulose chromatography, immunofluorescence, and radioimmunoassay. This procedure allowed specific and quantitative determination of chondrocytes in the presence of fibroblasts and myoblasts, both of which synthesize type I collagen. Chondrogenesis was studied in high-density cell preparations on tissue culture plastic dishes and on agar base. It was found that stage-24 limb mesenchymal cells initially synthesized only type I collagen. With the onset of chondrogenesis, a gradual transition to type II collagen synthesis was observed. In cell aggregates formed over agar, type II collagen synthesis started after 1 day in culture and reached levels of 80-90 percent of the total collagen synthesis at 6-8 days. At that time, the cells in the center of the aggregates had acquired the typical chondrocyte phenotype and stained only with type II collagen antibodies, whereas the peripheral cells had developed into a "perichondrium" and stained with type I and type II collagen antibodies. On plastic dishes plated with 5 X 10(6) cells per 35mm dish, cartilage nodules developed after 4-6 days, but the type II collagen synthesis only reached levels of 10-20 percent of the total collagen. The majority of the cells differentiated into fibroblasts and myoblasts and synthesized type I collagen. These studies demonstrate that analysis of cell specific types of collagen provides a useful method for detailing the specific events in the differentiation of mesenchymal cells in vitro.

Animals

Nicotinamide adenine dinucleotide levels in chick limb mesodermal cells in vitro: effects of 3-acetylpyridine and nicotinamide.

The studies reported here show that in cultures of developing mesodermal cells, chondrogenic expression is associated with a progressive decline in cellular NAD+ levels. Furthermore, reduced cellular NAD+ levels resulting from exposure to the nicotinamide analog 3-acetylpyridine are correlated with a 2- to 100-fold potentiation of chondrogenic expression. Conversely, elevated NAD+ levels resulting from exposure to nicotinamide alone are correlated with inhibition of chondrogenic expression. These data are consistent with the hypothesis that pyridine nucleotides, or some derivative thereof, play a central role in the control of muscle and cartilage development in embryonic chick limbs.

Animals