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Biomedical subjects

D M Fekete

Publications and source records attributed to D M Fekete.

36 records · Page 2Linked to original sources
PubMed1995

Assertive outreach for frequent users of psychiatric hospitals: a meta-analysis.

A meta-analysis was conducted on nine studies of an assertive outreach model for frequent users of psychiatric hospitals. Four studies used experimental or quasi-experimental designs and five used pre-post designs. Findings at one-year follow-up were examined for retention in community mental health services, psychiatric inpatient days, quality of life, and client level of functioning. Eighty-four percent of assertive outreach clients were still receiving mental health services after one year, compared to 54% of controls. In two thirds of the programs, the mean annual rate of inpatient days declined by 50% or more. The overall experimental effect size for quality of life was negligible, although changes over time for assertive outreach clients were more encouraging. Similarly, improvement in level of functioning was found for assertive outreach clients. The study examining experimental differences in level of functioning obtained a nonsignificant moderate effect.

Chicago↗
PubMed1994

Clonal analysis in the chicken retina reveals tangential dispersion of clonally related cells.

Development of the chicken retina was investigated through clonal analysis using retroviral vectors. Replication-incompetent retroviral vectors encoding either human placental alkaline phosphatase, beta-galactosidase, or a viral core protein were used in paired combinations to infect retinal progenitor cells from Embryonic Days 2.5-7.0. Labeled clones were analyzed late in embryonic development after retinal histogenesis was complete. The early accessibility of the chicken retina, combined with its large final size, resulted in the labeling of much larger clones than had been reported previously in other species. The clones were composed of many cell types, supporting previous conclusions from other vertebrates that the progenitor cells of developing retina are multipotent. The majority of clones derived from early infections consisted of multiple tightly clustered arrays of cells accompanied by dispersed individual cells. Clonal complexity and tangential dispersion were greater in peripheral than central retina and decreased considerably with increasing age of infection. These observations suggest that early during retinal development, shortly after optic cup formation, there is considerable mixing of progenitor cells.

Animals↗
PubMed1994

Asymmetric expression of a novel homeobox gene in vertebrate sensory organs.

A novel homeobox gene, SOHo-1, was isolated from embryonic chicken retina. On embryonic day 2 (E2), SOHo-1 is expressed in the retina, posterolateral otic pit, and neural tube anterior to the spinal cord. On E4, SOHo-1 is expressed at high levels in anterior retina and low levels in posterior retina, suggestive of a role in patterning the anterior-posterior axis. It is also expressed on E4 in the otocyst, the dorsal root ganglia, some cranial ganglia, and the second branchial arch. SOHo-1 expression in the otic pit and otocyst is restricted to regions that will give rise to the nonsensory tissues of the inner ear. SOHo-1 is not closely related to any identified vertebrate or Drosophila homeobox-containing genes. Since it is expressed in sensory-related structures and does not fit into existing classes of homeobox genes, we propose the name SOHo-1, for sensory organ homeobox-1.

Amino Acid Sequence↗
PubMed1993

Retroviral infection coupled with tissue transplantation limits gene transfer in the chicken embryo.

Gene transfer into early embryos is a powerful methodology for unraveling the molecular bases of developmental processes. One can attempt to minimize widespread effects of an exogenous gene by using tissue- or region-specific promoters in the few instances where they are available. We have developed a method that bypasses the requirement for specific targeting sequences to achieve regionally restricted gene transfer. Intraspecific chimeras have been created by transplantation of restricted portions of a chicken embryo from a donor strain to a host strain. The donor cells are infectable with a recombinant retroviral vector that carries the exogenous gene, whereas the host cells are not. We have demonstrated the feasibility of this approach using a histochemically distinct reporter gene, human placental alkaline phosphatase. The expression of retrovirally transduced alkaline phosphatase was limited to a transplanted hemiprosencephalon (forebrain and eye) in embryonic chickens. This technique can be applied to many other organ systems during avian embryogenesis to test the function(s) of molecules that are normally controlled through spatial and/or temporal regulation, such as many of the growth factor receptors or homeobox-containing proteins.

Animals↗
PubMed1993

Replication-competent retroviral vectors encoding alkaline phosphatase reveal spatial restriction of viral gene expression/transduction in the chick embryo.

Replication-competent avian retroviruses, capable of transducing and expressing up to 2 kb of nonviral sequences, are now available to effect widespread gene transfer in chicken (chick) embryos (S. H. Hughes, J. J. Greenhouse, C. J. Petropoulos, and P. Sutrave, J. Virol. 61:3004-3012, 1987). We have constructed novel avian retroviral vectors that encode human placental alkaline phosphatase as a marker whose expression can be histochemically monitored. These vectors have been tested for expression by introducing them into the embryonic chick nervous system. They have revealed that the expression of retrovirally transduced genes can be spatially and temporally limited without the need for tissue-specific promoters. By varying the site and time of infection, targeted gene transfer can be confined to selected populations of neural cells over the course of several days, a time window that is sufficient for many key developmental processes. The capability of differentially infecting specific target populations may avoid confounding variables such as detrimental effects of a transduced gene on processes unrelated to the cells or tissue of interest. These vectors and methods thus should be useful in studies of the effect of transduced genes on the development of various organs and tissues during avian embryogenesis. In addition, the vectors will facilitate studies aimed at an understanding of viral infection and expression patterns.

Age Factors↗
PubMed1989

Transient expression of simple epithelial keratins by mesenchymal cells of regenerating newt limb.

Structural proteins of the intermediate filament family are an early indicator of differentiation before organogenesis becomes apparent. Keratin intermediate filaments are characteristically expressed only by epithelial and not by mesenchymal cells. Here we show, using monoclonal antibodies, a transient expression of the keratin pair 8 and 18 in a population of mesenchymal cells in the regenerating newt limb, specifically in the undifferentiated progenitor cells (blastemal cells) which give rise to the new tissues. These keratins are also expressed in cultured limb cells that can differentiate into muscle. In contrast no reactivity with anti-keratin 8 and 18 antibodies was observed in the newt limb bud at an early stage of development, indicating a molecular difference between the developing and regenerating limb. The molecular weights of the newt proteins detected by these antibodies are very similar to those of human keratins 8 and 18, further supporting the immunocytochemical evidence that the newt homologs of these keratins are expressed in blastemal cells. This is the first demonstration of keratin expression in mesenchymal progenitor cells in an adult animal.

Animals↗
PubMed1988

Evidence that the nerve controls molecular identity of progenitor cells for limb regeneration.

Adult urodele amphibians can regenerate their limbs after amputation by a process that requires the presence of axons at the amputation plane. Paradoxically, if the limb develops in the near absence of nerves (the 'aneurogenic' limb) it can subsequently regenerate in a nerve-independent fashion. The growth zone (blastema) of regenerating limbs normally contains progenitor cells whose division is nerve-dependent. A monoclonal antibody that marks these nerve-dependent cells in the normal blastema does not stain the mesenchymal cells of developing limb buds and only stains the amputated limb bud when axons have reached the plane of amputation. This report shows that the blastemal cells of the regenerating aneurogenic limb also fail to react with the antibody in situ. These data suggest that the blastemal cells arising during normal regeneration have been altered by the nerve. This regulation may occur either at the time of amputation (when the antigen is expressed) or during development (when the limb is first innervated).

Animals↗
PubMed1987

A monoclonal antibody stains myogenic cells in regenerating newt muscle.

Monoclonal antibodies have been used to study minced muscle regeneration in the adult newt, Notophthalmus viridescens. The contralateral limb was amputated and the immunostaining patterns in the regenerating blastema were compared with the minced tissue in sectioned material. Staining with a myofibre-specific antibody, called 12/101 (Kintner & Brockes, 1984), showed that myofibre degeneration was complete by 8-10 days after mincing, with myogenesis commencing 2 days later. Another monoclonal antibody, called 22/18, previously shown to label a subset of cells in the regeneration blastema of the newt (Kintner & Brockes, 1984, 1985), was found also to recognize a population of cells in regenerating minced muscle. At 6 days after mincing, the number of 22/18-positive (22/18+) cells was low but by days 12-16, during the period of myogenesis, their number had increased to become a major population within the minced tissue. A small number of the 22/18+ cells could be double labelled with 12/101 at this time. Prior to this, there was a phase in which 12/101 staining had disappeared from the mince. Cells immunoreactive with both antibodies after this phase confirm that at least some of the 22/18+ cells are myogenic. The number of 22/18+ cells decreased as muscle repair and maturation progressed. These results show that 22/18 is not specifically associated with blastemal cells but is a more general marker for regenerating systems in the newt. They further suggest an alternative interpretation of the double-labelled cells used by Kintner & Brockes (1984) as evidence for myofibre dedifferentiation in limb regeneration. Instead, we propose that such cells represent new myogenesis occurring by tissue repair of locally damaged muscle fibres.

Animals↗
PubMed1987

A monoclonal antibody detects a difference in the cellular composition of developing and regenerating limbs of newts.

We have previously described a monoclonal antibody (called 22/18) that reacts with the early blastemal cells of the regenerating limb of the newt (Notophthalmus viridescens). In embryos of two newt species the antibody reacts with the epidermis, glial cells in the neural tube, the lens and cells in a restricted region of the aorta. In the developing limb bud less than 1% of the mesenchymal cells were reactive with 22/18, although most cells stained brightly with an antibody to another cytoskeletal component. When limbs were amputated prior to the arrival of nerves (axons and Schwann cells) at the amputation plane there was no extra reactivity with 22/18 as compared to the contralateral unamputated control, even though the amputated buds regenerated satisfactorily. Limbs amputated after nerves are present at the plane of amputation respond by forming a 22/18-positive blastema. The appearance of the 22/18 responses is a function of the stage of limb development as shown by amputation of forelimb and hindlimb buds at a larval stage where development of the forelimb is greatly advanced relative to the hindlimb. The distribution of the 22/18-positive cells in larval blastemas showed them to be closely associated with axons as detected by double staining with an antiserum to a neurofilament subunit. The clear antigenic difference between development and regeneration may be related to the relationship between embryonic regulation and epimorphic regeneration, and also to the acquisition of nerve-dependent proliferation of blastemal cells.

Animals↗
PubMed1986

The central projections of intracellularly labeled auditory nerve fibers in cats: an analysis of terminal morphology.

The axons of physiologically characterized spiral ganglion neurons (type I) were stained throughout their arborizations in the cochlear nucleus by the intracellular injection of horseradish peroxidase (HRP). The tips of the axonal branches were marked by distinct swellings, ranging in size and shape from small boutons to large perisomatic ramifications. Electron microscopic analysis of such swellings revealed ultrastructural features characteristic of primary auditory synapses, consistent with the hypothesis that terminal swellings identifiable in the light microscope represent presynaptic endings. On the basis of light microscopic differences in size, these endings were organized into three categories. Endings of relatively small size (terminal boutons, free endings, boutons with filopodia, string endings, and small complex endings) composed 94% of all terminal endings. Within this category of small endings, there were predictable variations in relative size and regional distribution that related to the spontaneous discharge rate (SR) of the fiber. The endings of low and medium SR fibers (SR less than or equal to 18 spikes/second) were smaller on average than those of high SR fibers (SR greater than 18 spikes/second). Furthermore, there were more endings arising from the ascending branch than from the descending branch when comparing fibers of the low and medium SR group with those of the high SR group. There were not, however, obvious morphological features of this ending category that correlated with the characteristic frequency (CF, the pure tone frequency to which the neuron is most sensitive). A second category contained medium-sized complex endings, most of which formed axosomatic contacts. This category composed 4% of the population and was found in close proximity to the perikarya of globular, octopus, and spherical cells. The endings from low and medium SR fibers were smaller on average than those from high SR fibers. These endings did not vary in their parent branch distribution with respect to fiber SR, nor did they exhibit morphological features that correlated with fiber CF. The third category contained large complex endings (endbulbs of Held) and composed 2% of the ending population. Within the anteroventral cochlear nucleus, these large, complex endings made axosomatic contact with spherical cells in the anterior division and with globular cells in the posterior division. There were no systematic variations in ending size or branch distribution that correlated with fiber SR. There was, however, a relationship between ending size and fiber CF such that fibers having CFs below 4 kHz gave rise to the largest endbulbs.

Action Potentials↗
PubMed1984

The central projections of intracellularly labeled auditory nerve fibers in cats.

The central projections of physiologically characterized auditory nerve fibers were studied in the cochlear nuclei of adult cats after intracellular staining with horseradish peroxidase (HRP). This technique consistently labels only the type I spiral ganglion neurons which contact inner hair cells in the cochlea (Liberman and Oliver, '84). The central axon of each type I neuron bifurcates in the cochlear nucleus to form an ascending branch and a descending branch. The characteristic frequency (CF) of a fiber corresponds to the dorsoventral position of these major branches and their collateral ramifications within the nucleus. Fibers of low CFs are distributed ventrally, and fibers of increasing CF are distributed progressively more dorsally. In some cases, the collateral branches deviate from this tonotopic arrangement, particularly in (1) the octopus cell region of the posteroventral cochlear nucleus, (2) the zone of bifurcations of the auditory nerve fibers, and (3) the anterior, dorsal, and lateral margins of the ventral cochlear nucleus. Spontaneous discharge rate (SR) is related to the complexity of the axon arbor, especially along the ascending branch. Fibers of low and medium SR exhibit more axonal branch points and longer collateral lengths than do those with high SR. Six of 37 labeled fibers fail to innervate the dorsal cochlear nucleus, a feature apparently unrelated to CF or SR.

Afferent Pathways↗
PubMed1983

The subcellular localization of rat photoreceptor-specific antigens.

The subcellular localization of three photoreceptor antigens (RET-P1, rhodopsin and RET-P2) has been studied by electron microscopic immunocytochemistry of rat retinas. Localization was also examined by determining the amount of RET-P1 and RET-P2 antigen in various subcellular fractions. RET-P1 and RET-P2 antigens were further characterized by immunoblotting of crude retina membrane proteins which had been separated by one-dimensional gel electrophoresis. RET-P1 antigen has been detected with a monoclonal antibody that reacts with the perikarya, inner segments, and outer segments of adult rat photoreceptors by peroxidase immunolabelling of fixed tissue sections. Analysis at the electron microscopic level has shown that RET-P1 antigen is located on the external face of the inner and outer segment plasma membrane. A monoclonal antibody against purified bovine rhodopsin (RHO-C7) labels the outer segments of rat retinas by peroxidase immunocytochemistry. Ultrastructural antibody localization indicates that this particular determinant of rhodopsin is exposed on the external face of the plasma membrane of outer segments and may also be expressed on the surface of the inner segments. RET-P2 antibody labels only the outer segments of adult rat photoreceptors by peroxidase immunocytochemistry. The light microscopic labelling of RET-P2 antibody in the presence, but not in the absence, of detergent suggests that it is an intracellular antigen. The results of both ultrastructural labelling and biochemical fractionation are consistent with the localization of RET-P2 antigen on the internal face of the plasma membrane and/or the cytoplasmic face of the disc membranes. RET-P2 antigen was found to be a protein (or glycoprotein) of apparent molecular weight 38 000 +/- 3000.

Animals↗
PubMed1982

Morphology of primary axosomatic endings in the anteroventral cochlear nucleus of the cat: a study of the endbulbs of Held.

The central axons of Type I spiral ganglion neurons travel in the auditory nerve and terminate in the cochlear nucleus. The ascending branches of these axons innervate the anteroventral cochlear nucleus and give rise to large axosomatic endings, called the endbulbs of Held, and smaller boutons. This paper reports a study of the endbulbs of Held, stained by horseradish peroxidase and variants of the Golgi method in kittens 2, 5, 10, 20, and 45 days postnatal and adult cats. Endbulbs tend to fall into two extreme groups with some endbulbs having an intermediate appearance; consequently, we have defined three descriptive stages of endbulbs that are conceived of as representing a developmental sequence. One group of endbulbs is found mostly in kittens younger than 10 days postnatal and is similar to the classic description of endbulbs by Ramón y Cajal ('09). The other extreme group of endbulbs is found mostly in adult cats. In these cases, the parent axonal trunk divides into several thick, gnarled branches that in turn branch again, sometimes repeatedly. These branches display irregular varicosities and form a cup-shaped arborization into which the postsynaptic cell body nestles. A chronology of postnatal endbulb development has been inferred from the relative proportions of the different endbulb stages at various ages. Maturation transforms the endbulb of Held from a large, spoon-shaped swelling having many filipodia into an elaborate tree with broad trunks and many smaller branches. Some implications of the proposed development sequence are discussed.

Aging↗
PubMed1981

Differential afferent projections to the inferior colliculus from the cochlear nucleus in the albino mouse.

The axonal projections from the cochlear nuclear complex to the inferior colliculus (IC) were examined using the retrograde transport of horseradish peroxidase. Thin sheets of neurons in the dorsal and ventral cochlear nuclei were found to project axons in a topographic fashion to restricted laminae of the central nucleus of the IC; the dorsal cochlear nucleus was also found to project axons to the external cortex. No projections were detected from the cochlear nuclear complex to the dorsal cortex of the IC.

Afferent Pathways↗
PubMedDate not supplied

Ventromedial focus of cell death is absent during development of Xenopus and zebrafish inner ears.

We present the normal patterns of programmed cell death in the developing inner ears of a primitive anuran, Xenopus laevis, and an ostariophysan fish, Danio rerio. A prominent ventromedial focus of cell death was described previously in the developing chicken and mouse otocysts. We hypothesize that this focus of cell death might be associated with a signaling center that directs morphogenesis of the surrounding tissue. Amphibian and fish ear anatomies differ considerably from those of birds and mammals, particularly in the structures derived from the ventral part (pars inferior) of the otic vesicle. We reasoned that these anatomical differences between species might result from a difference in the size, location, or presence of a putative morphogenetic signaling center. Using in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) to detect apoptotic cells, we show that developing Xenopus and zebrafish ears have apoptotic cells in the eighth cranial ganglia, the developing sensory patches, and in various positions in the otocyst wall. However, both species lack the persistent ventromedial hot spot of cell death that is prominently situated between the pars superior and pars inferior in the chicken and mouse otocysts.

Anatomy, Comparative↗
PubMedDate not supplied

In vivo gene transfer into the embryonic inner ear using retroviral vectors.

Retrovirus-mediated gene transfer holds great promise for elucidating key genes in the development and function of the inner ear. Retroviral vectors offer a number of advantages over other gene transfer methods including stable and efficient integration into the host genome, high levels of transcription and restriction of expression to a target area. Because of the wide variety of recombinant retroviral vectors currently available, this review outlines which vectors are appropriate for particular applications. Successful strategies for infecting the ear are reviewed and current drawbacks and future directions are discussed.

Animals↗