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Biomedical subjects

A Di Luzio

Publications and source records attributed to A Di Luzio.

15 recordsLinked to original sources
PubMed2000

Granule neuron DNA damage following deafferentation in adult rats cerebellar cortex: a lesion model.

Neuronal programmed cell death is regulated by a neurotrophic supply from targets and afferent inputs. The relative contribution of each component varies according to neuronal type and age. We have previously reported that primary cultures of cerebellar granule cells undergo apoptosis when deprived of depolarising KCl concentrations, suggesting a significant role of afferent inputs in the control of cerebellar granule cells survival. This issue was investigated by setting up various in vivo lesional paradigms in order to obtain partial or total deafferentation of the cerebellar granule layer in adult rats. At different times after surgery, cerebellar sections were subjected to TUNEL staining in order to detect possible DNA damage. One week after unilateral pedunculotomy, few scattered groups of apoptotic granule neurons were observed in the homolateral hemisphere. On the contrary, total deafferentation obtained by a new experimental paradigm based on an "L-cut" lesion induced massive and widespread apoptotic death in the granule layer of the deafferentated area. The time window of DNA fragmentation in granule layer was one to seven days after the "L-cut". Selective Purkinje cell deafferentation obtained by 3-acetylpyridine injection did not result in TUNEL staining in the cerebellar cortex. The current finding that mossy fiber axotomy induces granule cell apoptotic death points out for the first time the crucial role of afferent inputs in mature granule cell survival. Moreover, the in vivo lesional model described here may prove to be an useful tool for investigating cellular and molecular mechanisms of neuronal death triggered by deafferentation.

Afferent Pathways↗
PubMed1995

Neuroantibodies: ectopic expression of a recombinant anti-substance P antibody in the central nervous system of transgenic mice.

Recombinant antibodies are efficiently secreted by cells of the nervous system. Thus, their local expression in the CNS of transgenic mice could be used to perturb the function of the corresponding antigen. As a first application of this approach, we have generated transgenic mice that express antibodies against the neuropeptide substance P, under the transcriptional control of the promoter of the neuronal gene vgf. The transgenic antibodies are expressed in a tissue-specific and developmentally regulated manner and are effective in competing with the endogenous substance P, as demonstrated by a marked inhibition of neurogenic inflammation and by motor deficits. This phenotypic knockout approach may provide a complementary alternative to gene knockout by homologous recombination.

Animals↗
PubMed1992

A recombinant cell line expressing a form of the Y13-259 anti-p21ras antibody which binds protein A and may be produced as ascites.

We have recently reported the molecular cloning of the immunoglobulin genes encoding the variable regions of the rat anti-p21ras antibody, Y13-259. These genes were reassembled into expression vectors supplying DNA sequences encoding human gamma 1 and kappa constant domains, as well as the leader sequence for antibody secretion, thus yielding Hu-Y13-259, a secretory anti-p21ras antibody containing human constant regions. We now report the creation of a recombinant cell line, NS0/Hu-Y13-259/B6, secreting high levels of the Hu-Y13-259 Ig. The antigen specificity of this recombinant antibody was demonstrated to be identical to that of the parental Y13-259, i.e. the amino acid sequence 60-76 of the p21ras protein. Unlike the parental cell line, the recombinant cells could be grown as ascites in mice, allowing the production of large quantities of the protein A-binding Hu-Y13-259 antibody.

Animals↗
PubMed1991

Neuroantibodies: molecular cloning of a monoclonal antibody against substance P for expression in the central nervous system.

We present a strategy to study functional and/or developmental processes occurring in the nervous system, as well as in other systems, of mice. This strategy is based on the local expression of specific monoclonal antibodies (mAbs) by cells of the nervous system. As an application of this strategy, we report the cloning of the anti-substance P rat mAb NC1/34HL. Functional substance P-binding antibodies were reconstituted from the cloned variable domains by using vectors for expression in myeloma cells. With these and other vectors a general system for the cloning and expression of mAbs under a series of promoters (of the rat VGF8a gene, the neurofilament light-chain gene, and the methallothionein gene) has been created. The activity of these plasmids was confirmed by expressing the recombinant NC1/34HL mAb in GH3 pituitary cells, PC12 pheochromocytoma cells, and COS cells. DNA from the described constructs can be used to target the expression of the NC1/34HL mAb to the central nervous system of transgenic mice. This procedure will allow us to perturb substance P activity in a controlled way in order to dissect its multiple roles.

Amino Acid Sequence↗
PubMed1988

IFN-gamma facilitates NGF-induced neuronal differentiation in PC12 cells.

Natural or recombinant murine interferon-gamma causes a reversible arrest of proliferation of PC12 cells. Treatment with other antimitotics (AraC, colchicine, mitomycin C, hydroxyurea) or removal of serum, on the contrary, leads to mitotic arrest followed by cell death. IFN-gamma-treated PC12 cells respond more rapidly to NGF in terms of speed of neuronal outgrowth. On the other hand, NGF potentiates the action of IFN-gamma in stimulating the enzyme 2',5'-A synthetase which shifts from an average of 4.4-fold stimulation at 48 h with IFN-gamma alone to increments varying between 5- and 18-fold when PC12 cells are treated for 48 h with IFN-gamma and NGF. NGF alone, on the contrary, does not exert any detectable effect on this enzyme. From the findings we propose the use of a combined treatment of PC12 cells with NGF and IFN-gamma for a more rapid induction of neuronal differentiation.

Adrenal Gland Neoplasms↗
PubMed1983

[Correlations between dietetic fiber and serum levels of total cholesterol and HDL-cholesterol].

We have studied 10 male subjects, in good health to look for a probable correlation between dietetic fibre and serum concentration of total cholesterol, cholesterol-HDL and triglycerides. The dosages have been made before and immediately after that the subjects had assumed, with a diet, during 13 weeks, 10 g for day of dietetic fibre. The results show a significative statistical decrease and increase. Show a significative statistical decrease (p less than 0,025) of total cholesterol and that in agreement with the literature, and an increase (p less than 0,0125) of cholesterol-HDL. Consequently it's possible to affirm that the dietetic fibre has an antiatherogenic capacity.

Adolescent↗
PubMed1982

[Changes in hematologic parameters in 120 Somalian subjects].

We have studied in Somali subjects (120), compared with 120 Caucasus subjects the hemoglobin, the hematocrit, the number of red cells, the MCV, the MCH and MCHC. The results demonstrate that in Somali subjects have significant reduction of all parameters, and the reasons of those blood disorders in this tropical country must be associated with the scourges of poverty and malnutrition.

Adolescent↗
PubMed1982

[Study of T-lymphocyte subpopulations through monoclonal antibodies].

We studied the lymphocyte subpopulations T4+ and T8+ through monoclonal antibodies (McAb). The end of our study was focused in understanding the differences between the values mentioned by the literature and, consequently, determining our range of normality. Thus, we determined the subpopulations T4 and T8 using the antibodies OKT4 IND and OKT8 SUP, which define respectively the subpopulations T helper and T suppressor. Such determinations have been fulfilled whether on the total lymphocytes or on the lymphocytes T purified. Of course, the results obtained are different if we use the total lymphocytes or lymphocytes T purified. This confirms our suspect that the different values mentioned by the literature are determined by the two possible methods: T purified or total lymphocytes. In order to avoid interpretative mistakes, we suggest to express the values of T4+ and T8+ through the relation T4/T8; in fact, studying the single values obtained by the two different methods we proved they are different, but, at the same time, the relation T4/T8 remain unchanged in each method and is included in a "range of normality" from 1,4 to 1,7.

Antibodies, Monoclonal↗
PubMed1981

[HDL-cholesterol as an indicator of atherogenic risk in healthy women of advanced age].

We wanted to study HDL cholesterol in female subjects in good health but of in advanced age without a history of cardiac-vascular problems. The result show an increase in value for total cholesterol in only 2 subjects out of a total of 39 subjects studied and we saw a triglycerides increase in only 7 subjects. The HDL cholesterol was found high in 13 subjects and inferior to 55 mg/dl of serum in 26 subjects which also demonstrated low values of total cholesterol. In fact, the arteriosclerotic risk factor calculated using the method of Castelli e Cell increased only in 2 subjects demonstrating that the lack of clinical manifestation in accompanied by a decrease in the ateriosclerotic "risk factor".

Aged↗