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Biomedical subjects

A A Moscona

Publications and source records attributed to A A Moscona.

At least 19 recordsLinked to original sources

Measured femoral density by dual-energy X-ray absorptiometry as a function of rotation.

The use of projectional techniques to evaluate bone density of the proximal femur has the potential to be adversely affected by rotation along the head/condyle axis, due to the complex geometry of the region being examined. To experimentally investigate the magnitude of variation attributable to rotation, the bone density of a cadaveric femur, placed in a water bath to simulate soft tissue, was measured as a function of rotation by using a dual-energy x-ray absorptiometry (DXA) system. It was found that 10 to 15 degrees of rotation was the minimum deviation from the baseline of the femoral head perpendicular to the x-ray beam required to produce statistically significant (P = .95) changes in measured bone density. The magnitude of the variation at these rotations ranged from 2.5% for the trochanter to 5.0% for the femoral neck. Even though variation along the axis described is difficult to precisely control in the clinical setting, the magnitude of density errors attributable to these variations should not adversely affect the utility of projectional density measurement techniques.

Absorptiometry, Photon↗

Expression of v-src in embryonic neural retina alters cell adhesion, inhibits histogenesis, and prevents induction of glutamine synthetase.

Using Rous sarcoma virus as the vector, v-src or c-src genes were introduced into 6-day chicken embryo retina tissue in organ culture and their effects on retina development were investigated. Overexpression of c-src in many of the cells had no noticeable effect on retina development. In contrast, infection with v-src resulted in abnormal histogenesis and inhibition of differentiation. Although only a portion of the cells in infected tissue expressed the oncogene and displayed the transformation phenotype, the other cells were also hindered from becoming normally positioned and organized. Therefore, presence of oncogene-transformed cells within the tissue hindered organization and development of adjacent nontransformed cells. Failure of normal cell relationships impeded induction by cortisol of glutamine synthetase in Muller glia, which requires contact associations of the glia cells with neurons. The transformed cells tended to assemble into chaotic clusters, suggesting that their adhesiveness and contact affinities had become altered. This was confirmed by aggregation experiments with dissociated cells which showed that adhesiveness of transformed cells was greatly reduced and that they had lost the ability to cohere with nontransformed cells. In binary mixtures of transformed and nontransformed cells, the two sorted out into separate aggregates. Transformed cells formed loose clusters devoid of tissue architecture; aggregates of nontransformed cells became organized into retinotypic structures, and glutamine synthetase was inducible. Our findings suggest that the mechanisms of cell adhesion and cell affinities are a key target of v-src activity in infected cells and that modification of the cell surface may be a leading factor in other cellular changes characteristic of the v-src transformation phenotype.

Animals↗

Anatomy of the pancreas and Langerhans islets in snakes and lizards.

The pancreas of snakes (18 species) was comparatively examined and classified into five major types, based on structure of the lobes and ducts, spatial relationships with the spleen and the gall bladder, and the disposition of islet cells. These types trend toward fusion of the pancreatic lobes and compaction of the pancreas--a progression that coincides with the phylogeny of the snakes. The more primitive pancreas of lizards (17 species) also was surveyed; that of Varanus is of special interest because its structure is intermediate between the extended, tri-lobate pancreas of lizards and the compact pancreas of snakes and may represent a transitional link in the evolution of this organ. Islet tissue is always confined to the dorsal lobe and is concentrated in its distal region adjacent to the spleen. In primitive snakes and in Varanus, a large islet mass is sequestered within a distinct juxtasplenic "islet body" distanced from the dorsal lobe and connected to it by a slender stalk. In some of the most advanced snake species, numerous islets of endocrine cells are found within the spleen. The occurrence and formation of these intrasplenic islets is described in detail. The anatomic "affinity" between spleen and the islet region of the pancreas is discussed. A hypothesis for the development of the pancreas from embryonal placodes on the mid-gut is presented; it proposes that the exocrine and the endocrine components derive from different progenitor cells, and that the endocrine progenitors are located in the center of the dorsal placode. The hypothesis combines embryological and evolutionary views about the origin of the pancreas, and offers a rationale for differences in its structure and in the disposition of the islets.

Animals↗

Quantitative dual-energy radiographic absorptiometry of the lumbar spine: in vivo comparison with dual-photon absorptiometry.

Quantitative dual-energy radiographic absorptiometry (DRA) and dual-photon absorptiometry (DPA) were compared to determine the best means of assessing bone density. Both methods were used to evaluate the lumbar spine in 107 women (aged 35-84 years [mean, 64 years]) referred for evaluation of osteoporosis risk. High correlation was documented between measurements derived by the two techniques, with a .95 linear regression coefficient for the total spine density measurement. Age-related regression equations were similar in slope but manifested different intercepts. Bone mineral density values derived with DRA were consistently lower than those obtained with DPA (conversion equation: DPA density = [1.067 X DRA density] + 0.163). Besides the inherent imperfections of each system, it was found that inaccurate identification of intervertebral spaces on the low-resolution DPA images introduced errors in patient data. DRA may replace DPA as the dedicated projectional densitometric procedure of choice for technical reasons, but at present a conversion equation must be used to compare DRA data to DPA data.

Adult↗

Embryonic cell recognition: uncoupling tissue-specific affinities from cell-type specificities.

We have experimentally defined the two major aspects of embryonic cell recognition-adhesion (ReAd), tissue type-specific ReAd and cell type-specific ReAd; we showed that they arise consecutively during cell differentiation, and that the former can function in the absence of the latter. Embryonic chick cells (retina and chondroblasts) in which differentiation was arrested by BrdU at an early stage, failed to express cell-type ReAd, yet they continued to display tissue-type ReAd: they distinguished tissue-self from non-self and selectively cohered with self. Our results indicate that tissue-type and cell-type ReAd represent distinct, separately controlled mechanisms. BrdU appears to be useful as a probe for investigating the regulation of these mechanisms, and as an experimental effector of differentiation abnormalities associated with defects in cell recognition.

Animals↗

Cell contacts are required for induction by cortisol of glutamine synthetase gene transcription in the retina.

In embryonic neural retina the enzyme glutamine synthetase [GS; L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] is a glia-specific differentiation marker inducible with cortisol. We show that cortisol elicits GS mRNA accumulation by stimulating transcription of the GS gene and that this stimulation requires cell contacts: in dissociated and separated retina cells GS gene transcription was not induced; when the separated cells were reassembled into multicellular aggregates, restoring cell contacts, accumulation of GS mRNA was again inducible. In cells dissociated from retina tissue that had been preinduced with cortisol, GS gene transcription rapidly declined, despite continued hormone availability. In the separated cells transcription of the histone H3.3 gene and accumulation of carbonic anhydrase II mRNA were unaffected; therefore, cell separation selectively precluded induction of the GS gene. These findings provide direct evidence for the regulatory role of cell contacts in hormonal control of gene transcription.

Animals↗

Retinoic acid inhibits conversion of dissociated Müller glia into lens-like cells.

In monolayer cultures of dissociated retina cells, Müller gliocytes undergo conversion into a lens-like cell type (lentoidal cells): they become unable to adhere to neurons and accumulate lens antigens. Retinoic acid (RA) retards these changes. We present evidence that RA prevents the rapid loss of gliocyte adhesivity to neurons; and that, by promoting restoration of glia cell contacts with neurons, RA protects the gliocytes from phenotype alteration.

Animals↗

Developmental regulation of glutamine synthetase and carbonic anhydrase II in neural retina.

Glutamine synthetase (GS) is expressed in the neural retina only in Muller glia cells and is inducible with cortisol. A chicken genomic clone that contains at least part of the coding region for the GS enzyme was used to investigate developmental changes in the level of GS mRNA in embryonic chicken retina. A major GS transcript (approximately equal to 3 kilobases) detected by the probe begins to accumulate sharply on day 15 of embryonic development. When cortisol is prematurely supplied to early embryonic retina, it induces precocious accumulation of GS mRNA and of the GS enzyme. At later ages, these effects of cortisol are significantly greater, which suggests that competence to transcribe or stabilize GS mRNA in response to stimulation with cortisol increases with development. Carbonic anhydrase II (CA-II) is expressed in early retina in all the cells, but it becomes later restricted to Muller glia. Using cloned CA-II cDNA, we detected a high level of CA-II mRNA in early retina, followed by a decline due to arrest of CA-II mRNA accumulation in differentiated neurons. As glia cells mature, CA-II mRNA and the enzyme increase to a new high level. Therefore, changes in CA-II gene expression during retina development reflect differentiation-dependent cell-type-specific control of CA-II mRNA accumulation.

Age Factors↗

Accumulation of c-src mRNA is developmentally regulated in embryonic neural retina.

Accumulation of c-src mRNA gradually increased during early development of the neural retina in chicken embryos and reached a peak by days 11 to 13 of embryonic life. Thereafter, its amount declined to a low level which persisted also in adult retina. The early increase in c-src mRNA correlated inversely with the decrease in the amount of H3.2 replication histone mRNA and with the decline in the rate of cell growth. The accumulation profile of c-src mRNA corresponded to that of pp60c-src protein, suggesting that the latter is regulated at the level of transcription.

Animals↗

Formation of lentoids from retina gliocytes: ultrastructural study.

In primary monolayer cultures of dispersed neural retina cells from 13-day chick embryo, gliocytes (Müller glia cells) multiply and rapidly change into a lentoidal (lens-like) phenotype. They express lens proteins, including MP26 (a lens plasma-membrane antigen) and ultra-structurally appear to resemble lens cells. A significant aspect of this modification is that the glia-derived lentoidal cells no longer display contact-affinity for neurons but become preferentially adhesive to each other; in aggregates, they assemble into compact lentoids. A likely explanation for this change in cell affinities is that the modified gliocytes express little or no R-cognin, a retinal cell-surface antigen implicated in mutual recognition and adhesion of retina cells. Although lentoidal cells express MP26, a gap-junction component in the lens, no gap junctions could be found in the lentoids.

Animals↗

Cortisol receptors and inducibility of glutamine synthetase in embryonic retina.

Glutamine synthetase (GS) is a marker enzyme for Müller glia cells in neural retina. In chick embryo retina GS begins to increase sharply on the 16th day of development, but can be precociously induced by premature supply of the inducer, cortisol, already on the 8th day. At this stage GS inducibility is low, but it increases progressively with embryonic age. We investigated whether there was a corresponding age-dependent increase of cortisol-binding molecules (cortisol receptors) and found that their level is highest in the early retina and decreases with development. In light of this inverse relationship, we examined whether functional characteristics of these receptors change with age, but detected no differences. In in vitro tests, receptors from older retina translocated cortisol into nuclei from young retina, and vice versa, with similar effectiveness. Also, cortisol receptors from liver cells (which differ from retina receptors) can translocate the hormone into retina nuclei, and vice versa. These findings indicate that translocation of cortisol receptors is neither tissue-specific or age-dependent, nor is it conditional on the total amount of receptors normally present in cells. Therefore, the age-dependent increase of GS inducibility in embryonic retina cannot be directly related to quantitative or functional differences of cortisol receptors and is evidently controlled primarily at the gene level. The very large amount of cortisol-binding molecules in early embryonic retina raises the possibility that they play some role in early differentiation of retina cells unrelated to hormone binding.

Animals↗

Gangliosides in postmitotic retina of chick embryo: changes in vivo and in cell cultures.

Developmental changes in ganglioside composition of postmitotic neural retina of chick embryo were analyzed by thin-layer chromatography. Gangliosides were identified by comparing their chromatographic mobilities with reference standards. The outstanding changes are decrease in the concentration of GD3L and increase in GD1a and GM1 concentrations. By depleting Müller glia cells from retina tissue of 13- and 16-day embryos (R13, R16) we determined that the bulk of the major gangliosides is associated with the neurons. Analysis of gangliosides in monolayer cultures of R13 and R16 cells highly enriched for Müller cell-derived gliocytes indicated that these cells express the same types of gangliosides as neurons, but in somewhat different concentrations and relative proportions; however, after time in culture these cells showed ganglioside types and changes in ganglioside profile that are not characteristic of normal retina. The latter observation is consistent with other evidence that the phenotype of Müller glia cells becomes altered in monolayer culture. In contrast to cultures of early embryonic retina, in organ cultures of later postmitotic retina, ganglioside composition did not continue to change as in normal development. This suggests that in postmitotic retina, normal developmental progression of ganglioside changes requires systemic and/or other conditions which are missing or altered when this tissue is isolated and cultured in vitro.

2-Aminoadipic Acid↗

Antiserum to lens antigens immunostains Müller glia cells in the neural retina.

Antiserum to a lens fraction enriched for alpha-crystallin selectively immunostains Müller glia cells in the neural retina of several vertebrate species. Also, in embryonic retina (chicken), this antiserum reacts with Müller cells and, at early stages of development, with their apparent precursors. Thus, antibodies to a lens product(s) detect a Müller glia cell marker that begins to be expressed very early in their ontogeny and can be useful in studies on differentiation, function, and pathologies of this cell type.

Animals↗