Search PubMed⌕ Search

Biomedical subjects

M Del Monte

Publications and source records attributed to M Del Monte.

At least 19 recordsLinked to original sources
PubMed2003

A multicentre randomised double masked clinical trial of a new formulation of topical cysteamine for the treatment of corneal cystine crystals in cystinosis.

AIM: To evaluate the safety and efficacy of a new topical cysteamine formulation, stable at room temperature, for the treatment of corneal cystine crystals in cystinosis. METHODS: 20 study subjects were enrolled in the safety study and 16 in the efficacy study. Both studies were randomised and double blind. The primary outcome for the safety study was the occurrence of predefined serious adverse reactions over 6 months and for the efficacy study the reduction of corneal cystine crystal score (CCCS) by 1.00 or more units on photographs graded by a reading centre using a standardised protocol. RESULTS: No study subject developed any serious adverse reactions. In the efficacy study, 47% of eyes receiving the standard formulation experienced a reduction in the CCCS of >/=1.00 after 1 year, while 7% of eyes on the new formulation experienced such a decrease (p=0.04). CONCLUSION: Although no serious adverse reactions were observed with either formulation, the new formulation was not as effective as the standard formulation.

Administration, Topical↗
PubMed2001

Evidence of pre-industrial air pollution from the Heads of the Kings of Juda statues from Notre Dame Cathedral in Paris.

Pollution originating from wood combustion characterised the urban atmospheres of the past and led to the formation of thin grey crusts on the surface of the stone of monuments. The grey crusts discovered on the Heads of the Kings of Juda statues, which adorned the facade of Notre Dame in Paris from the 13th century until 1792, constitute a material record of the effects of this ancient air pollution. The height at which the statues stood suggests that the effect was not the result of a point phenomenon, but was caused by a generalised pollution of the Paris atmosphere at the time.

Air Pollution↗
PubMed1995

Expression and chromosomal localization of cDNA clones from an enriched human retinal pigment epithelial (RPE) cell line library: identification of two RPE-specific genes.

We have previously constructed an enriched cDNA library from a human retinal pigment epithelium (RPE) cell line and generated expressed sequence tags (ESTs) from novel clones. Here, we report the analysis of expression of 14 cDNAs and identify two clones, AA1 and AA28, that appear to be specifically expressed in RPE but not in any other tissue tested. We have also localized 15 novel cDNAs (including the two RPE-specific cDNAs) to human chromosomes using in situ hybridization or in conjunction with somatic cell hybrid analysis. The cDNAs were mapped to the following chromosomal regions: 1p35-->p33, 1q41-->q42 (two clones), 3q11.2-->q13.1, 3q24-->q25, 4q13-->q21, 6q22-->q23, 7q34-->q36, 10q23-->q24, 11q23-->q24, 15q25-->q26, 19p13.3, 20p13, 21q11.2-->q21, and 21q22.2-->q22.3. The genetic and functional analysis of the two RPE-specific genes should contribute to a better understanding of RPE function. Chromosomal localization of RPE cDNAs will be valuable in identifying candidate genes for inherited diseases involving RPE dysfunction and aid in establishing the expression map of the human genome.

Blotting, Northern↗
PubMed1993

Altered aldose reductase gene regulation in cultured human retinal pigment epithelial cells.

Aldose reductase (AR2), a putative "hypertonicity stress protein" whose gene is induced by hyperosmolarity, protects renal medullary cells against the interstitial hyperosmolarity of antidiuresis by catalyzing the synthesis of millimolar concentrations of intracellular sorbitol from glucose. Although AR2 gene induction has been noted in a variety of renal and nonrenal cells subjected to hypertonic stress in vitro, the functional significance of AR2 gene expression in cells not normally exposed to a hyperosmolar milieu is not fully understood. The physiological impact of basal AR2 expression in such cells may be limited to hyperglycemic states in which AR2 promotes pathological polyol accumulation, a mechanism invoked in the pathogenesis of diabetic complications. Since AR2 overexpression in the retinal pigment epithelium has been associated with diabetic retinopathy, the regulation of AR2 gene expression and associated changes in sorbitol and myo-inositol were studied in human retinal pigment epithelial cells in culture. The relative abundance of aldehyde reductase (AR1) and AR2 mRNA was quantitated by filter hybridization of RNA from several human retinal pigment epithelial cell lines exposed to hyperglycemic and hyperosmolar conditions in vitro. AR2 but not AR1 mRNA was significantly increased some 11- to 18-fold by hyperosmolarity in several retinal pigment epithelial cell lines. A single cell line with a 15-fold higher basal level of AR2 mRNA than other cell lines tested demonstrated no significant increase in AR2 mRNA in response to hypertonic stress. This cell line demonstrated accelerated and exaggerated production of sorbitol and depletion of myo-inositol upon exposure to 20 mM glucose. Therefore, abnormal AR2 expression may enhance the sensitivity of cells to the biochemical consequences of hyperglycemia potentiating the development of diabetic complications.

Actins↗
PubMed1991

Extracellular matrix mediated growth and differentiation in human pigment epithelial cell line 0041.

Efforts to grow differentiated pigment epithelial cells have led to a characterization of the growth kinetics of spontaneously established, continuously growing, human retinal pigment epithelial (PE) cell line 0041 on several biomatrices. These substrates were prepared from (a) placental and amniotic membrane, (b) commercially available basement membrane matrix (Matrigel), (c) dishes coated with extracellular matrix secreted by endothelial cells (ECM), (d) dishes coated with collagen IV and/or laminin, (e) dishes coated with collagen I and/or fibronectin. Our findings suggest that tissue culture plastic and dishes coated with collagen IV alone promote higher cell densities, while highest plating efficiency (24 hrs) was seen on tissue culture plastic and Matrigel. The highest degree of differentiation (epithelioid appearance, apical villi and junctional complexes) was seen in cells plated on dishes coated with collagen IV and extracellular matrix secreted by endothelial cells. Cells were epithelioid and polarized on those two substrates; they expressed fine finger-shaped villi and the highest degree of cell contact (in the form of junctions). Cells grown on Matrigel looked like fibroblasts and became deeply pigmented; however, the nature of the pigment remains to be determined. Collagen IV and ECM coated dishes, therefore, are most suitable for cultures of human PE cell line 0041 because they provide higher cell densities while retaining the differentiated state. This is the first report where an established pigmented epithelial cell line has been induced to become differentiated by use of extracellular matrices and extracellular matrix components.

Adolescent↗
PubMed1990

Ganglion-blocking agents enhance neurally mediated bronchoconstriction in the guinea-pig: possible role of sensory neuropeptides.

The effect of ganglion blockade by hexamethonium bromide (0.1-100 mumol.kg-1) and pentolinium tartrate (0.01-3 mumol.kg-1) on the bronchoconstriction induced by vagal nerve stimulation (15 Hz, 0.2 ms, 3 s, 7-20 V) was evaluated in the anaesthetized guinea-pig. Both ganglion-blocking agents potentiated this response dose dependently. When the neural bronchoconstriction was suppressed by atropine, hexamethonium restored this response dose dependently. Hexamethonium produced inhibitory effects on vagally induced bronchoconstriction in capsaicin-desensitized and in propranolol- or reserpine-pretreated guinea-pigs. Propranolol (0.03-3 mumol.kg-1) produced a marked dose-dependent increase of neural bronchoconstriction (which was markedly reduced, about 10 times) in capsaicin-desensitized animals. Our results show that ganglion-blocking agents potentiate neural bronchoconstriction in the guinea-pig and that sensory neuropeptides may have a role in this effect. Moreover, beta-adrenergic modulation of the release of neuropeptides from vagal sensory fibers is suggested.

Anesthesia↗
PubMed1990

Mechanism of the potentiation of neurally-induced bronchoconstriction by gallamine in the guinea-pig.

1. Electrical stimulation of the cervical vagi (15 Hz, 0.2 ms, 3 s, 7-15 V) produced a slight bronchoconstriction in the anaesthetized guinea-pig. This effect was fully abolished by atropine, while gallamine (0.1-10 mumol kg-1) produced a dose-dependent increase up to ten fold. 2. Gallamine-induced potentiation of neurally-mediated bronchoconstriction was not inhibited by depletion of sensory neuropeptides with capsaicin or by pretreatment with pyrilamine. In propranolol-pretreated guinea-pigs the potentiation induced by gallamine 3 and 10 mumol kg-1 was inhibited by 40 and 46%, respectively. 3. Physostigmine (0.5 mg kg-1) produced a very slight and slowly developing bronchoconstriction in the anaesthetized guinea-pig, which was also potentiated dose-dependently by gallamine (0.1-10 mumol kg-1). 4. Gallamine (10 mumol kg-1) potentiated the bronchial anaphylactic response induced by aerosol challenge with ovalbumin in actively sensitized guinea-pigs. 5. These results suggest that neither sensory neuropeptides nor histamine are involved in the gallamine-induced potentiation of neurally-mediated bronchoconstriction, while inhibition of the sympathetic nervous system may play a minor role. They are in general agreement with the hypothesis that gallamine antagonizes acetylcholine selectively at prejunctional muscarinic receptors in the guinea-pig airways, thus increasing its release from parasympathetic nerve terminals. These autoreceptors appear to be operant during anaphylactic bronchoconstriction.

Acetylcholine↗
PubMed1990

Establishment of human retinal pigment epithelial cell lines by oncogenes.

The primary human retinal pigment epithelial cells were transfected with oncogenic sequences derived from viruses and cellular homologues of retroviral oncogenes 'protooncogenes' linked to simian virus 40 (SV-40) and retroviral promoters. Foci of cells were noted between 2 to 4 weeks after transfection. Individual colonies of cells were expanded from cultures transfected with SV-40 virion DNA, SV-40 large T antigen gene, Ha-ras oncogene, human and mouse c-myc and adenovirus E1A gene. Established cell lines tested were positive for the specific oncogene sequences by Southern hybridization and also expressed the protein as assayed by immunofluorescence and immunoblot analysis. Cell lines established with SV-40 large T antigen, and SV-40 virion DNA, exhibited epithelioid morphology up to the 25th passage and later became more rounded. However, all cell lines established with other oncogenes continued to retain epithelial morphology. Functional analysis of the cell lines demonstrated the presence of polarity and the ability to phagocytize rod outer segments, characteristics of retinal pigment epithelial cells. The use of oncogenes with immortalization/transformation potential may allow the establishment of cell lines from ocular tissues for analysing the biochemical basis of a disease like retinitis pigmentosa.

Antigens, Polyomavirus Transforming↗
PubMed1989

In vitro phenotypic and functional characterization of human pigment epithelial cell lines.

We have characterized human retinal pigment epithelium (HRPE) for the expression of cell surface antigens. Primary HRPE cultures, established cell lines, and freshly brushed pigment epithelial cells all express HLA-ABC but not HLA-DR antigens. However, both primary cultures and established cell lines can be induced by gamma interferon stimulation to express HLA-DR in a dose dependent manner. Only freshly brushed HRPE cells express Fc, and no cells demonstrated the presence of C3b. Our results show that HRPE cells change in culture, as reflected by the loss of Fc receptors, but retain the ability to synthesize HLA-ABC spontaneously and HLA-DR upon stimulation.

Adolescent↗
PubMed1989

Advanced xerophthalmia as a presenting sign in cystic fibrosis.

Xerophthalmia is a common complication of vitamin A deficiency in communities where malnutrition is found. We report on a 16-month-old infant with severe photophobia and failure to thrive. On examination, her major presenting sign was corneal xerosis, with corneal and conjunctival keratinization, and corneal stromal edema with opacification. Based on these findings, vitamin A deficiency secondary to fat malabsorption was suspected, and a workup confirmed the diagnosis of cystic fibrosis. With parenteral vitamin A supplementation, she had complete resolution of her ocular signs and symptoms. This case illustrates the value of a complete ophthalmic examination in the diagnosis of fat malabsorption syndromes.

Conjunctival Diseases↗
PubMed1988

Platelet-activating factor-induced contraction of guinea-pig lung parenchymal strips: possible involvement of arachidonate metabolites.

The identification of the mediators possibly involved in platelet-activating factor (PAF)-induced contraction of guinea-pig lung parenchymal strips (GPLP) was attempted by means of antagonists and inhibitors. Histamine, serotonin, acetylcholine (ACh) or other transmitters released from the nerve terminals are not likely to play a role in this response, since specific antagonists and tetrodotoxin did not affect the contraction. PAF antagonists (brotizolam and WEB 2086) produced a concentration-dependent inhibition of the contraction. Inhibitors of TXA2 synthesis (dazoxiben) and of 5-lipoxygenase (nordihydroguaiaretic acid and AA 861) and antagonists of TXA2 (ICI 159995) and peptidoleukotrienes (L 649923 and LY 171883, but not FPL 55712) produced a significant inhibition of the PAF-induced response at concentrations which did not reduce the ACh-induced response. These results suggest that arachidonate metabolites, both of the cyclo-oxygenase and of the lipoxygenase pathway, are determinants of the PAF-induced contraction of GPLP.

Acetylcholine↗
PubMed1988

Effects of anti-asthma drugs on PAF-induced death in mice.

A number of anti-asthma drugs was assayed for the ability to protect mice from platelet-activating factor (PAF)-induced death, which has been suggested to be dependent on the bronchoconstrictive features of this autacoid. Salbutamol, dexamethasone, theophylline, ketotifen and zindotrine, administered parenterally, produced a dose-dependent protection, while forskolin, enprofylline, disodium cromoglycate, nedocromil, azelastine and antagonists of acetylcholine, histamine and serotonin were devoid of protective effects. Theophylline, contrary to salbutamol, lost its protective effects in adrenalectomized mice, suggesting that these effects are dependent on the release of adrenomedullary cathecolamines. Salbutamol, theophylline and dexamethasone, at doses capable of inhibiting PAF-induced death, did not affect PAF-induced haemoconcentration in mice, thus excluding widespread changes in vascular permeability as a major cause of death. These results are generally in agreement with the hypothesis that airway obstruction is an important determinant of PAF-induced death in mice.

Adrenalectomy↗
PubMed1988

Mechanisms of the antiallergic action of N-methylmequitazine (LG 30435).

LG 30435 (N-methylmequitazine) was assayed in passive lung (PLA) and cutaneous (PCA) anaphylaxis in guinea-pigs and rats. At doses from 0.3 to 3 mumol kg-1 i.v., it produced a dose-dependent inhibition of guinea-pig PLA and of rat PCA and PLA, while the parent compound was ineffective or poorly effective up to 3 mumol kg-1. An attempt was made to elucidate the mechanism of LG 30435's action in these anaphylactic models, by means of various antagonists. It was tentatively concluded that different mechanisms are involved in the protective action of LG 30435 in each of the three models: histamine antagonism, possibly accompanied by an inhibition of the effects of peptido-leukotrienes in guinea-pig PLA; histamine antagonism in rat PCA and 5-hydroxytryptamine antagonism in rat PLA, possibly accompanied by a mast-cell stabilizing action in both cases. LG 30435 is devoid of smooth muscle relaxant effects on the airways and its demonstrated anticholinergic and anti-PAF effects do not appear to be involved in its antiallergic action.

Anaphylaxis↗
PubMed1985

Isoprene metabolism by liver microsomal mono-oxygenases.

Mouse-liver microsomal mono-oxygenases metabolize isoprene to the corresponding mono-epoxides. The reaction was NADPH- and O2-dependent and was inhibited by CO, SKF525-A and metyrapone. 3,4-Epoxy-3-methyl-1-butene was the major metabolite of isoprene, and the kinetic constants (Km and Vmax) for this epoxidation were determined by analysing the corresponding diol by g.l.c. in incubations with microsomes from control or pretreated mice. 3,4-Epoxy-2-methyl-1-butene was a minor metabolite (approx. 20%). 3,4-Epoxy-2-methyl-1-butene was epoxidated further to the mutagenic isoprene dioxide by microsomes from control or pretreated mice. The Km and Vmax were determined and phenobarbital shown to be an inducer of this epoxidation.

Animals↗
PubMed1984

Dinemorphan N-demethylation by mouse liver microsomes.

Dinemorphan, an antitussive drug, is N-demethylated in vitro by mouse liver microsomes with biphasic kinetics showing two apparent Km and Vmax. Moreover, dinemorphan N-demethylation is inhibited by CO, SKF-525A, metyrapone and it is specifically catalyzed by a phenobarbital-inducible form of cytochrome P-450.

Animals↗
PubMed1980

Simultaneous correction of blepharoptosis and exotropia in aberrant regeneration of the oculomotor nerve by strabismus surgery: a new, simplified ptosis correction for selected cases.

Selected patients with blepharoptosis and exotropia with aberrant regeneration of the oculomotor nerve can achieve acceptable cosmesis by simple strabismus surgery. Patients with good lid position on attempted contralateral gaze are candidates for this new approach. With aberrant regeneration of the oculomotor nerve, the affected levator frequently becomes pathologically yoked to the contralateral lateral rectus muscle. In these cases, the ecotropia is corrected by a recess-resect procedure primarily or exclusively on the contralateral fixing eye such that postoperatively. The fixing eye is "abducted" by the patient to the primary position, and the ptotic lid elevates simultaneously.

Blepharoptosis↗