Development Of Various Tissues Research Articles

Inhibition by dehydroepiandrosterone of growth and progression of persistent liver nodules in experimental rat liver carcinogenesis.

Dehydroepiandrosterone (DHEA) inhibits the development of early pre-neoplastic lesions and prevents tumor development in various tissues when given to animals during the initiation/promotion stages of carcinogenesis. Our purpose was to evaluate whether DHEA can also arrest the growth and progression of late lesions, such as persistent nodules (PNs) of rat liver. Male F344 rats were subjected to initiation by diethylnitrosamine followed by selection according to the "resistant hepatocyte" (RH) protocol. Fifteen weeks after initiation, when PNs were present in the liver, the rats were fed a diet with/without 0.6% DHEA for a maximum of 15 weeks. Glucose-6-phosphate dehydrogenase (G6PD) activity was 17- to 20-fold higher in PNs than in normal liver 15-30 weeks after initiation. It significantly decreased, in both liver and PNs, 16 hr after starting DHEA feeding. Further DHEA feeding for 3-15 weeks decreased G6PD activity by 55-58% in both tissues. Eight weeks after starting DHEA, a fall in the proportion of labeled cells, after continuous contact with 3H thymidine for 7 days, was found in nodules. Treatment for 15 weeks with DHEA caused a marked decrease in the number of nodules per liver, as well as in the incidence of PNs with diameters of 3-6 and > 6 mm, respectively, while it did not affect PNs with diameters < 3 mm. Nodules showing patterns of malignant transformation were present in 40% of rats not treated with DHEA, but not in DHEA-treated rats. All of 8 surviving rats not treated with DHEA had carcinomas at the 56th week, while only 1 out of 4 surviving rats treated with DHEA had carcinoma. These data indicate that DHEA inhibits G6PD activity in rat liver and in PNs in vivo. This is associated with growth restraint of PNs and results in inhibition of their progression to malignancy.

Antigen-receptor cross-linking induces peritoneal B-cell apoptosis in normal but not autoimmunity-prone mice

Background: Programmed cell death (apoptosis) is an essential process in the development of various tissues and seems to be involved in the elimination of self-reactive immature T and B lymphocytes when they interact with self antigens. Indeed, signaling through the antigen receptor of immature T cells induces their apoptotic cell death. Immature B cells have also been shown to be eliminated when they interact with antigens, although the involvement of apoptosis has yet to be demonstrated. In contrast, little is known about the elimination of mature lymphocytes upon interaction with antigens. We have previously demonstrated that Ly1 B cells in the peritoneal cavity of transgenic mice undergo apoptotic cell death upon interaction with antigens. As Ly1 B cells constitute a B-cell lineage distinct from conventional B cells, it is important to know whether conventional B cells also undergo apoptosis upon antigen-receptor cross-linking.Results Our experiments show that, in vivo, strong cross-linking of cell-surface immunoglobulins induced apoptotic death of normal, mature B cells in the peritoneal cavity, regardless of whether they were conventional or Ly1 B cells. The same treatment did not kill, but rather activated, B cells in bcl-2-transgenic, apoptosis-resistant mice. Peritoneal B cells from autoimmune-disease-prone New Zealand mouse strains were also found to be resistant to cell death induced by surface immunoglobulin cross-linking.Conclusion Self-reactive B cells are eliminated by the binding of antigen at both mature and immature stages. B-cell activation appears to require, in addition to antigen binding, a second signal that induces expression of rescue molecules such as the bcl-2 gene product. Resistance to B-cell apoptosis induced by antigen receptor cross-linking may play a crucial role in the production of autoantibodies and in the pathogenesis of the autoimmune diseases found in the strains of mice used here.

Expression of FGF receptor gene in rat development.

We examined the expression of FGF-receptor (FGF-R) mRNA during rat development with in situ hybridization histochemistry. Embryonic tissues (E9, E12, E14, E17) and postnatal neural tissues (P1, P7, P14, adult) were examined. We detected significant levels of FGF-R mRNA in various tissues at different developmental stages. As postulated by previous studies using other methods, FGF-R gene expression was observed primarily in mesoderm- and neuroectoderm-derived tissues. In the nervous system, the pattern of gene expression was developmentally regulated; in embryos, FGF-R mRNA was mainly detected in the ependymal layer of the central nervous system (CNS). Postnatally, FGF-R transcripts were observed in specific neuronal populations, such as hippocampal neurons. FGF-R mRNA was also found in sensory systems such as trigeminal and dorsal root ganglia in late stage embryos; however, FGF-R mRNA decreased in the postnatal period. FGF-R mRNA expression was modulated in the developing retina: FGF-R messages were observed in the pigment epithelium and neuroblast layer at embryonic stages; in the postnatal period, they were found in the ganglion cell and inner granular layer. In non-neuronal embryonic tissues, a wide variety of organs expressed FGF-R message. Particularly, the prevertebral column, bone, kidney and skin showed high levels of expression. These observations reinforce the idea that FGF exerts effects on the development of various tissues.

Effects of maternal nephrectomy on foetal kidneys.

RESEABCH on the general phenomenon of compensatory organ growth is usually predicated on the assumption that humoral growth-regulating factors must exist as a logical, though hypothetical, necessity. Yet their unequivocal demonstration is, unhappily, a very rare event indeed. If our knowledge of the control mechanisms which govern the growth and development of various tissues and organs is to parallel that which has followed the discovery of erythropoietin, for example, and its role in stimulating erythropoiesis, then it is imperative that the existence of tissue-specific stimulators or inhibitors be experimentally demonstrated. Until this is achieved, the validity of many theoretical interpretations must remain in question.

Pseudophyllidean Cestodes from Alaskan Pinnipeds

Some thirty-three species of pseudophyllidean cestodes have been described from seals and sea-lions but the descriptions are so incomplete and imperfect that it is virtually impossible to recognize any of them with certainty. Redescriptions of species, on the basis of incorrectly determined specimens, have undoubtedly added to the confusion. In the absence of information concerning life cycles, consideration must be given to the possibility that representatives of a single species may complete their development in different host species and furthermore that, as a result of development in different hosts, individuals of the same species may manifest differences in size and shape, in rate of growth and sexual maturity, and in extent of development of various tissues and organs. Consequently, specific determination of specimens presents a particularly difficult problem. The pseudophyllidean cestodes of seals and sea-lions have been assigned to nine different genera, but the generic concepts are so indefinite and their limits are so poorly defined that there is no agreement concerning either the number of valid species or the generic groups to which they should be allocated. The uncertainty and confusion regarding the morphology and taxonomy of these cestodes were discussed by many earlier authors and more recently by Mueller (1937) and Wardle, McLeod and Stewart (1947). Most of the species have been referred, at one time or another, to the genus Diphyllobothrium Cobbold, 1858 as emended by Liihe (1910). The genus Diphyllobothrium, as defined by Liihe, is a heterogeneous assemblage and taxonomic revision of these tapeworms was proposed by Mueller (1937) and by Wardle, McLeod and Stewart (1947). The latter authors stated: is a cumbersome group of about 70 species-many of them of dubious validity-and comprises forms from toothed-whales, seals, sea-lions, carnivorous land mammals and fisheating birds. Several species have been recorded from humans and one even from a snake. It has always been an unsatisfactory genus to define and analyze, and particularly difficult to evaluate have been the forms from seals and sea-lions that have been recorded by numerous writers. Wardle et al erected a new genus, Cordicephalus, to contain the species found in seals-and sea-lions and recognized four species: Cordicephalus phocarus (Fabricius, 1780) ; C. tectus (Linstow, 1892); C. arctocephalinus (Johnston, 1937) ;and C. quadratus (Linstow, 1892). All other species from seals and sea-lions were regarded as identical with one or other of the four accepted species. The remaining species of Liihe's genus were distributed among six other genera: Diphyllobothrium Cobbold, 1858; Diplogonoporus Loennberg, 1892; Dibothriocephalus Liihe, 1899; Glandicephalus Fuhrmann, 1921 ; Adenocephalus Nybelin, 1931; and Spirometra Mueller, 1937.