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Biomedical subjects

A Harel

Publications and source records attributed to A Harel.

At least 37 records · Page 2Linked to original sources
PubMed1989

Optic nerve regeneration in adult fish and apolipoprotein A-I.

Fish optic nerves, unlike mammalian optic nerves, are endowed with a high capacity to regenerate. Injury to fish optic nerves causes pronounced changes in the composition of pulse-labeled substances derived from the surrounding non-neuronal cells. The most prominent of these injury-induced changes is in a 28-kilodalton (kDa) polypeptide whose level increases after injury, as revealed by one-dimensional gel electrophoresis and autoradiography. The present study identified as apolipoprotein A-I (apo-A-I) a polypeptide of 28 kDa in media conditioned by regenerating fish optic nerves. The level of this polypeptide increased after injury by approximately 35%. Apo-A-I was isolated by gel-permeation chromatography from delipidated high-density lipoproteins (HDL) that had been obtained from carp plasma by sequential ultracentrifugation. Further identification of the purified protein as apo-A-I was based on its molecular mass (28 kDa) as determined by gel electrophoresis, amino acid composition, and microheterogeneity studies. The isolated protein was further analyzed by immunoblots of two-dimensional gels and was found to contain six isoforms. Western blot analysis using antibodies directed against the isolated plasma protein showed that the 28-kDa polypeptide in the preparation of soluble substances derived from the fish optic nerves (conditioned media, CM) cross-reacted immunologically with the isolated fish plasma apo-A-I. Immunoblots of two-dimensional gels revealed the presence of three apo-A-I isoforms in the CM of regenerating fish optic nerves (pIs: 6.49, 6.64, and 6.73). At least some of the apo-A-I found in the CM is derived from the nerve, as was shown by pulse labeling with [35S]methionine, followed by immunoprecipitation. The apo-A-I immunoactive polypeptides in the CM of the fish optic nerve were found in high molecular-weight, putative HDL-like particles. Immunocytochemical staining revealed that apo-A-I immunoreactive sites were present in the fish optic nerves. Higher labeling was found in injured nerves (between the site of injury and the brain) than in non-injured nerves. The accumulation of apo-A-I in nerves that are capable of regenerating may be similar to that of apo-E in sciatic nerves of mammals (a regenerative system); in contrast, although its synthesis is increased, apo-A-I does not accumulate in avian optic nerves nor does apo-E in rat optic nerves (two nonregenerative systems).

Animals↗
PubMed1989

Persistence of major nuclear envelope antigens in an envelope-like structure during mitosis in Drosophila melanogaster embryos.

Using monoclonal antibodies, we followed the fate of three different nuclear envelope proteins during mitosis in Drosophila early embryos by indirect immunofluorescence microscopy. Two of these proteins, lamin and otefin, a newly characterized nuclear envelope polypeptide with an apparent Mr of 53,000, are apparently present in an envelope-like structure that is present throughout mitosis. Immunoelectron microscopy of interphase nuclei indicates that otefin, like lamin, is not a component of nuclear pore complexes. In contrast with lamin and otefin, gp188, a putative pore complex component, was completely redistributed through the surrounding cytoplasm during prophase in comparable early embryo specimens and was present in an envelope only in interphase. Together with previous morphological studies by other workers, these data suggest that the entire mitotic apparatus including condensed chromosomes and spindle is enclosed by an envelope throughout mitosis during early embryogenesis in Drosophila. This 'spindle envelope', as it has been named by others, contains both lamin and otefin but probably not pore complex proteins.

Animals↗
PubMed1988

Interactions between human and carp (Cyprimus carpio) low density lipoproteins (LDL) and LDL receptors.

1. We have compared the concentration and chemical composition of carp and human plasma lipoproteins and studied their interaction with human fibroblast LDL receptors. 2. The main lipoproteins in carp are of high density (HDL) in contrast to low density lipoproteins (LDL) in human. 3. Carp lipoproteins are devoid of apolipoprotein (apo) E, a major ligand for interaction with LDL receptors in mammals. 4. Carp very low density lipoproteins (VLDL) and LDL but not HDL nor apoA-I cross react with human LDL in their interaction with LDL receptors on human cultured fibroblasts. 5. Carp liver membranes possess high affinity receptors that are saturable and have calcium dependent ligand specificity (apoB and apoE) similar to human LDL receptor. Carp VLDL and LDL but not HDL nor its major apolipoprotein complexed to L-alpha-phosphatidylcholine dimyristoyl (apoA-I-DMPC) competed with the specific binding of human LDL to this receptor.

Adult↗
PubMed1988

Optic nerve regeneration--new aspects.

Injury to the optic nerve and its environment provokes a process of degeneration that leads to a degenerative process resulting in an irreversible loss of visual function. We succeeded in stimulating regeneration in injured optic nerves of adult rabbits. The stimulus to regeneration was achieved by implanting in injured optic nerves of adult rabbits substances originating from growing (regenerating) optic nerves of fish or developing optic nerves of neonatal rabbits, and by delaying the degenerative process by irradiating the injured optic nerve with a low energy laser. The effect was manifested by abundant growth of new fibers across the injury site and by other manifestation of regeneration characteristics.

Animals↗
PubMed1987

Morphological response of injured adult rabbit optic nerve to implants containing media conditioned by growing optic nerves.

Adult rabbit retina can express regeneration-associated characteristics after optic nerve injury, provided it is supplied with appropriate diffusible substances originating from media conditioned by regenerating fish optic nerves or by optic nerves of a newborn rabbit [Hadani et al., Proc. Natl. Acad. Sci. U.S.A., 81 (1984) 7965; Schwartz et al., Science, 228 (1985) 600]. This was shown by applying the active substances to the injured axons in the form of 'wrap-around' implants, consisting of collagen-coated silicone tubes which had been soaked in the conditioned media (CM). The regeneration-associated response was manifested biochemically and by sprouting of nerve fibers in culture. The present work provides morphological evidence that the implantation prolongs survival of ganglion cells and optic nerve fibers and induces new growth. Light microscopic analysis (using horseradish peroxidase (HRP) for labeling the fibers) revealed, 1 week following optic nerve injury, labeled fibers and ganglion cells in both the implanted and control (injured only or injured and implanted with collagen-coated silicone tubes free of CM) nerves. However, from the second week after the injury, distinct differences in the appearance of viable ganglion cells and labeled fibers, were seen between experimental and control preparations. In sections taken through the optic nerve, at the region distal to the site of injury, HRP-labeled fibers were seen in the experimental nerves 1 week, 2 weeks and to a significantly lesser extent 1 month after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Laminin-immunoreactive sites are induced by growth-associated triggering factors in injured rabbit optic nerve.

We have previously demonstrated that application of soluble growth-associated triggering factors (GATFs) from regenerating fish optic nerve or neonatal rabbit optic nerve to a non-regenerative crushed adult rabbit optic nerve provokes regeneration-like changes in the adult rabbit. In this study we show that the responses initiated by GATFs also include a change in pattern of appearance of an extracellular matrix component, laminin, known to play a role in neurite outgrowth and elongation. These findings suggest a mechanism whereby GATFs activate the adult rabbit glial cells to produce or to accumulate laminin and thereby allow partial compensation for the low inherent regenerative ability of the adult rabbit optic nerve.

Animals↗
PubMed1987

Environmental changes induced by growth-associated triggering factors in injured optic nerve of adult rabbit.

Central nervous system (CNS) neurons of mammals regenerate poorly after axonal injury. However, if an injured CNS neuron (rabbit optic nerve) is supplied with appropriate soluble substances ("growth-associated triggering factors") derived from medium conditioned by regenerating fish optic nerve or newborn rabbit optic nerve, it can express regeneration-associated characteristics. Such characteristics include a general increase in protein synthesis, changes in synthesis of specific polypeptides, and sprouting of nerve fibers in culture. The present study of rabbit optic nerves demonstrates that such active substances affect the neuronal environment (i.e., the non-neuronal cells), thereby perhaps causing a shift in the environment from an inhibitory to a regenerative supportive one. Apparently, such an environment is spontaneously achieved in injured CNS nerves of lower vertebrates (e.g., fish optic nerves), which are regenerable. Treatment of injured rabbit optic nerve with soluble factors from medium conditioned by regenerating carp optic nerve resulted in a selective increase in proliferation ([3H]thymidine incorporation) of perineural cells and the appearance of a 12-kDa polypeptide in a homogenate derived from the nerve and its associated cells. This polypeptide may be related to growth, since it comigrates in NaDodSO4/polyacrylamide gel electrophoresis with a 12-kDa polypeptide that is continuously present in a regenerative system. In addition, there were injury-induced changes in the polypeptides of the nerve that were independent of treatment with conditioned medium and were correlated with nerve maturation. The most prominent changes of this type were in 18-kDa and 25-kDa polypeptides whose levels were reduced after injury and were found to be correlated with the nerve maturation (myelination) state.

Animals↗
PubMed1987

Molecular and cellular aspects of axon-glia interaction in CNS regeneration.

The relationships of neurons and non-neuronal cells are vital for the maintenance and function of neurons. Trauma alters these relationships causing proliferation of non-neuronal cells and, in adult mammalian CNS, presumably disturbs the environmental support needed for regeneration. A supportive environment can be restored by introducing a regenerating nerve to injured mammalian CNS. This response is probably due, at least in part, to diffusible substances secreted by the non-neuronal cells. We have obtained diffusible substances from either regenerating fish optic nerves or neonatal rabbit optic nerves and applied them around crushed adult rabbit optic nerves. This manipulation caused the adult nerve to show regenerative changes: a general increase of protein synthesis in the retinas; selective increase in synthesis of a few polypeptides in the retinas; sprouting from the retinas in vitro; increased viability of nerve fibers as shown by HRP staining; and the appearance of growth cones adjacent to glial limitans in the injured nerves. We termed these diffusible, active substances "Growth Associated Triggering Factors" (GATFs). In addition to the phenomena described above, the active substances (obtained in the form of media conditioned by regenerating fish optic nerve or neonatal rabbit optic nerve) caused various other changes in the injured nerve itself: acceleration of non-neuronal cell proliferation; changes in the protein pattern, e.g. an increase in a 12 kDa polypeptide which might be a second mediator in the cascade of events leading to regeneration; increased laminin immunoreactive sites in the nerve; and the acquisition of growth supportive activity in media conditioned by the implanted injured nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Regenerating fish optic nerves and a regeneration-like response in injured optic nerves of adult rabbits.

Regeneration of fish optic nerve (representing regenerative central nervous system) was accompanied by increased activity of regeneration-triggering factors produced by nonneuronal cells. A graft of regenerating fish optic nerve, or a "wrap-around" implant containing medium conditioned by it, induced a response associated with regeneration in injured optic nerves of adult rabbits (representing a nonregenerative central nervous system). This response was manifested by an increase of general protein synthesis and of selective polypeptides in the retinas and by the ability of the retina to sprout in culture.

Animals↗
PubMed1985

A new transorbital surgical approach to the rabbit's optic nerve.

This work describes a surgical approach which establishes the rabbit's visual system as an experimental model for studying CNS regeneration. Using this model, the optic nerve, its cell bodies, and the axons, are easily accessible through an orbital approach, without the need for craniotomy and brain retraction. This surgical approach allows transplantation and 'wrap around' implantations of nerve segments from xenogeneic and syngeneic systems and diffusible substances derived from them, respectively. Furthermore, it enables studies aimed at determining deficiencies in mammalian CNS and investigating methods of augmentating mammalian CNS regeneration.

Animals↗
PubMed1985

Alterations in mRNA translation products associated with regenerative responses in the retina.

Translation products of mRNA from retinas of goldfish optic nerve (representing a regenerative CNS) and adult rabbit optic nerve (representing a nonregenerative CNS which can be induced to express regenerative characteristics) were examined by one- and two-dimensional gel electrophoresis. Translation products from retinas of the regenerating goldfish optic nerve included polypeptides barely detectable in the translation products of mRNA derived from retinas of uninjured controls. Some of these polypeptides, of apparent molecular weights 24-28, 43-49, 60, and 65 kilodaltons can be considered as growth-associated polypeptides described in other regenerative and developing systems. The induction of regeneration-associated characteristics in the injured adult rabbit optic nerve, "implanted" with diffusible substances from nonneuronal cells of regenerative or growing nerve, is reflected by changes in the mRNA translation products of the retina. Among such translation products are those of the following molecular weights: 16-18, 28, 32-35, 43-47, and 56-60 kilodaltons, and some higher-molecular-weight species.

Animals↗
PubMed1984

Substances originating from the optic nerve of neonatal rabbit induce regeneration-associated response in the injured optic nerve of adult rabbit.

We have recently shown that cell bodies of an injured optic nerve of adult rabbit can be induced to express regeneration-associated response by external signals derived from nonneuronal cells of regenerating nerves of lower vertebrates. In this study it is shown that even substances derived from a nonregenerating mammalian system also can trigger such a regenerative response. Thus, substances derived from intact nerves of neonatal rabbits and of adult rabbits, to a lesser extent, were active in triggering a regeneration-associated response, whereas substances derived from injured nerves of adult rabbit were not. However, if subsequent to the injury the nerve was implanted with silicone tube containing medium conditioned by neonatal optic nerves, the substances derived from the implanted injured nerve were active. Thus, it appears that the ability of a periaxonal environment to provide triggering substances correlates with axonal growth. Therefore, we named these substances "growth-associated triggering factors" (GATFs). It is suggested that mammalian cells are unable to express a regenerative response after an injury due to the failure of their nonneuronal cells to produce regeneration-triggering substances. This disability may be circumvented by an appropriate implantation procedure.

Aging↗
PubMed1984

Accessory function and interleukin 1 production by human leukemic cell lines.

Highly purified T lymphocytes do not proliferate in response to mitogens, unless adherent HLA-DR-positive monocytes are added to the culture. This accessory function (AF) of monocytes requires the release of interleukin 1 (IL 1). Cells from three human leukemic cell lines, K562, HL60, and U937, could very efficiently replace monocytes in a 72-hr mitogen-induced T cell proliferation assay. The AF was clearly related to precise maturational stages of these cells; the hematopoietic precursor K562 cells spontaneously exerted high AF, but lost this property when treated with differentiation inducers. On the contrary, the promyelocytic HL60 cells and the "histiocytic" U937 cells exhibited no spontaneous AF, but acquired this property when induced to differentiate along the granulocytic and/or monocytic pathway. Three leukemic cells could not only stimulate T cells to proliferate and produce IL 2 in the presence of mitogens, but also under appropriate culture conditions these cells could produce IL 1, which could not be distinguished from normal human monocyte derived IL 1 by gel filtration and isoelectric focusing. Moreover, analysis of phenotypic markers revealed that AF and production of IL 1 could be demonstrated in different cell types and therefore are not restricted to the monocytic lineage. No HLA-DR antigen could be detected on K562 and HL60 cells. Thus, the expression of the DR antigens is not required for AF and IL 1 production in response to mitogens. These three human leukemic cell lines will provide convenient sources of human IL 1.

Cell Line↗
PubMed1983

Leukemia cell lines can replace monocytes for mitogen-induced T-lymphocyte responses: this accessory function is dependent upon their differentiation stage.

Highly purified peripheral T lymphocytes do not proliferate in response to phytohemagglutinin A or concanavalin A, unless adherent HLA-DR+ monocytes are added as accessory cells. The accessory function (AF) of monocytes is mediated through the release of interleukin-1 (IL-1). We here report that cells from three human leukemic lines--K562, HL-60, and U-937--could exert AF and efficiently replace monocytes in a 72-hr mitogen-stimulated proliferation assay. This AF was clearly related to precise maturational stages of these cells, since the hematopoietic precursor K562 cells spontaneously exerted high AF but lost this property when treated with differentiation inducers such as sodium butyrate or phorbol 12-myristate 13-acetate (PMA). On the other hand, untreated HL-60 and U-937 cells exhibited no spontaneous AF, but they acquired this function when induced to differentiate either along the granulocytic pathway (dimethyl sulfoxide-treated HL-60 cells) or along the monocytic pathway (PMA-treated HL-60 and U-937 cells). Supernatants from PMA-triggered K562 or HL-60 cells allowed the proliferative response of murine thymocytes to phytohemagglutinin A and were therefore shown to contain IL-1. Analysis of phenotypical markers showed that AF and IL-1 production were not restricted to cells of the monocytic lineage. No HLA-DR antigen could be detected on K562 and HL-60 cells. Thus, the expression of HLA-DR antigens is not required for AF and IL-1 production in response to mitogens. Human leukemia cell lines could provide useful sources of human IL-1.

Cell Differentiation↗
PubMed1983

Congenital absence of scalp skin and herpes simplex virus. A case report.

A male infant, born at 40 weeks' gestation of a 27-year-old mother, presented at delivery with three scalp lesions, 2 to 4 cm in diam, covered with necrotic tissue and devoid of hair. The infant was born by natural vertex delivery within 2 hours of membrane rupture; birth weight was 3,300 g and Apgar score 10. There were no other skin lesions, and physical and neurological examinations were normal. Herpes simplex virus Type 2 was isolated from the lesions and the mother's cervix. High titers of IgG and IgM antibodies in the serum of mother and infant indicated an intrauterine infection. The skin ulcers healed within 1 month, with gradual epithelization and formation of a hairless atrophic scar.

Adult↗