Biomedical subjects

L Gabriel

Publications and source records attributed to L Gabriel.

At least 19 recordsLinked to original sources

PubMed1993

Cytoskeletal modifications induced by 4-hydroxynonenal.

The antiproliferative action of 4-hydroxynonenal (HNE) could be related to an interaction with cytoskeletal structures. In this paper the effects exerted by HNE on microtubules and on microfilaments are examined by immunofluorescence. HNE alters cell morphology causing both the depolymerization of the microtubular structures and the dissolution of the stress-fibres. Taxol protects microtubules, preventing the depolymerizing effect of the aldehyde. The action of HNE could be attributed to its affinity for sulphydryl groups, which are essential in maintaining tubulin and actin both in the polymerized form.

3T3 Cells↗

PubMed1992

Aldehyde-induced modifications of the microtubular system in 3T3 fibroblasts.

The molecular structure of aldehydes is closely related to their antimicrotubular effect. Morphological modifications of the microtubular system in living cells after incubation with certain aldehydes are consistent with biochemical alterations detected in previous research. The microtubular arrangement was visualized by an immunofluorescence technique with antitubulin antibodies, while the content of tubulin in the cells was evaluated by a colchicine binding assay. 2-Nonenal behaved similarly to 4-hydroxynonenal, a lipid peroxidation product, disorganizing microtubular network in 3T3 fibroblasts and decreasing the amounts of tubulin able to bind labelled colchicine. Nonanal did not significantly impair the tubulin characteristics in the cells, despite the fact that it has been shown to be active on the purified microtubular system; benzaldehyde was ineffective. This would appear to explain the mechanisms of interaction of aliphatic aldehydes which might be suitable for use as antimicrotubular drugs.

3T3 Cells↗

PubMed1991

Effects of some aldehydes on brain microtubular protein.

4-Hydroxynonenal is one of the main breakdown products of lipid peroxidation. It has an antiproliferative effect, which may partly be the consequence of an interaction with cytoskeletal structures. Its effects on microtubular protein are compared with those of homologous aldehydes with the same number of carbon atoms, and with that of benzaldehyde. Unlike the other aliphatic aldehydes, this latter aldehyde does not impair microtubular functions at every concentration in the range. Nonanal has the greatest effect on tubulin polymerization, whereas it only slightly impairs colchicine binding activity. 2-Nonenal and 4-hydroxynonenal have less inhibiting effect on tubulin polymerization; their effect on colchicine binding activity is dose-dependent. The targets of 4-hydroxynonenal on tubulin are -SH groups; the action mechanism of other aldehydes has not yet been identified.

Aldehydes↗

PubMed1991

Interaction of C-9 aldehydes with microtubular protein in vitro and in cultured cells in the presence of taxol.

Some aldehydes have previously been shown to alter the microtubular system in a concentration-dependent manner. This paper examines the effects of taxol on the impairment of in vitro functionality of microtubular protein and of cytoplasmic microtubules by C-9 aliphatic aldehydes. Taxol-induced polymerization was inhibited by aldehydes in a similar way to GTP-induced polymerization, even though to a different degree. The addition of taxol restored the ability of aldehyde-impaired tubulin to polymerize, but only in the presence of nonanal. Colchicine binding activity in the presence of taxol was slightly modified by aldehydes at 20 degrees C, while it increased at 37 degrees C, compared to controls. Immunofluorescence showed a low disruption of microtubules in fibroblasts incubated with aldehydes and pretreated with taxol, probably as a consequence of its stabilizing activity. Anyway, aldehydes studied behaved differently, indicating a structure-activity relationship.

3T3 Cells↗

PubMed1990

4-Hydroxynonenal interacts with tubulin by reacting with its functional -SH groups.

4-Hydroxynonenal, which is one of the most important products of lipid peroxidation, alters microtubular organization and structure in 3T3 fibroblasts. Changes in cell shape and the disappearance of microtubules are observed by immunofluorescence after incubation with the aldehyde, and the colchicine binding activity of tubulin from 3T3 cells is modified. Moreover, the aldehyde determines a decrease in the ability of purified tubulin to polymerize and to bind colchicine. These effects may be related to the interaction of the aldehyde with functional -SH groups of tubulin which are necessary for protein integrity and functions. Indeed, the addition of cysteine protects against the damaging effects of the aldehyde.

Aldehydes↗

PubMed1990

The fine structural localization of endogenous and exogenous peroxidase activity in human bone marrow mast cells under pathological conditions.

We have examined the ultrastructural characteristics of peroxidase activity in human bone marrow mast cells. These studies were performed in three patients with systemic mast cell disease, and in another six patients showing bone marrow mast cell hyperplasia. Endogenous peroxidase activity was localized in the perinuclear cisternae and strands of endoplasmic reticulum, but never in the granules. We have also demonstrated the "in vivo" existence of exogenous peroxidase activity in two of the three cases of systemic mast cell disease. The peroxidase internalization involved its binding to the plasma membrane, followed by its incorporation into the cell by a general endocytic process comprising the uptake of dispersed peroxidase-positive material mainly by phagocytosis of granular structures containing peroxidase. The exogenous peroxidase appeared in non-membrane bound granules, vacuoles or aggregates, but we have never seen the enzyme linked to the mast cell granules.

Adult↗

PubMed1990

Evaluation of a sick child day care program: lack of detected increased risk of subsequent infections.

A day care center for the short term care of mildly ill children opened in Minneapolis in October, 1985. We conducted a prospective study to evaluate the risk for study participants of acquiring subsequent infections as a result of possible exposure to other infectious agents while at the center. Between June, 1986, and August, 1987, we determined the rates of subsequent infections for 118 children attending the day care center (center-based children) and compared them with rates of subsequent infections for children participating in a home-based sick child care program (home-based children). Of 105 center-based children potentially exposed to respiratory illness while at the center, 24 (23%) developed subsequent respiratory illness compared with 17 (16%) of the matched home-based children (odds ratio, 1.5; 95% confidence interval, 0.7, 3.1). Of 17 center-based children potentially exposed to gastrointestinal illness, 1 (6%) developed subsequent gastrointestinal illness compared with one (6%) of the matched home-based children (odds ratio, 1.0; 95% confidence interval, 0.06, 16.0). Of 12 pairs of children, where the center-based child was potentially exposed to chickenpox while at the center and both were susceptible to chickenpox, 1 center-based child (8%) developed chickenpox compared with 2 home-based children (17%) (odds ratio, 0.5; 95% confidence interval, 0.04, 5.5). We were not able to demonstrate that children who attended the sick child day care center were at significantly increased risk of developing subsequent infections when compared with a matched group of children who did not attend the center.

Chickenpox↗

PubMed1990

Effect of calvatic acid and its analogs on ornithine decarboxylase activity in tumour cells.

Calvatic acid (p-carboxyphenylazoxycyanide) is an antibiotic containing an azoxycyano group that displays carcinostatic activity. In the present work it has been shown that in AH-130 hepatoma and K562 leukemia cells the antibiotic, at low concentration, decreases ornithine decarboxylase (ODC) levels. The change depends on two summative effects of the drug, impairment of overall protein synthesis and inhibition of enzyme activity. Some analogs of calvatic acid have been tested in order to gain more insight into the structure-activity relationship. The decarboxylated derivative phenylazoxycyanide proved to be more effective in reducing protein synthesis and ODC activity in the whole tumor cells. The rapidly growing K562 cells displayed high sensitivity to this compound. Calvatic acid analogs devoid of the cyano group were less effective on the same parameters.

Animals↗

PubMed1989

Angioid streaks in homozygous beta thalassemia.

One hundred patients with homozygous beta thalassemia (62 had beta thalassemia major and 38 had beta thalassemia intermedia) were examined by ophthalmoscopy for angioid streaks. Angioid streaks were found in 20 patients from both the beta thalassemia major and beta thalassemia intermedia groups (nine and 11 patients, respectively). A positive correlation was found between age and angioid streaks (P = .0017), as was a difference in the prevalence of angioid streaks between the two forms of the disease (P = .079). Additionally, a significant correlation was noted between chelating therapy and the prevalence of angioid streaks (P = .039). However, using multivariate analysis to correct for the effects of age, the correlation of angioid streaks with the form of disease disappeared, whereas the level of significance between chelation therapy and angioid streaks was reduced (P = .05). The high frequency of angioid streaks observed in patients with beta thalassemia and the severe complications observed in one patient render a thorough ophthalmoscopic examination and follow-up of such patients necessary for both early diagnosis and possible therapeutic intervention.

Adolescent↗

PubMed1989

Phenylazoxycyanide damages microtubular protein more than its reference antibiotic, calvatic acid.

The effect of phenylazoxycyanide and calvatic acid, its reference antibiotic, on some functions of tubulin obtained from different sources has been studied. Our purpose was to establish a possible correlation between the antitumour activity of these drugs and their antimicrotubular action. Microtubules are subcellular structures involved in proliferation and maintenance of the cell shape and probably in malignant transformation; indeed most antimitotic drugs influence the stability of microtubules through the interaction with tubulin, their main protein. In this work we found phenylazoxycyanide impairs, more than calvatic acid, polymerization of purified tubulin from calf brain. It also damages, in a dose-dependent manner, colchicine-binding ability of tubulin derived from rat liver and AH-130 Yoshida ascite hepatoma cells. Compounds displaying an azoxycyano group may represent new antimicrotubular agents and their effect could be modulated by the different polarity and structural characteristic of the molecule.

Animals↗

PubMed1988

Stage I intraoperative adjustment of eye muscle surgery under general anesthesia: consideration of graduated adjustment.

The eyes diverge under general anesthesia. The amount of divergence is predictable; there is a linear relationship between the preoperative and the anesthetized eye position. We have confirmed Apt and Isenberg's regression formula for this relationship (A = 0.8 P + 30). We have previously also reported that adjusting the amount of surgery to be done (stage I adjustment) in cases deviating from this correlation by one standard deviation or more (anomalous) significantly improved our surgical success rate to 85%. Since a fixed arbitrary adjustment of 1 mm more or less surgery had improved our surgical success rate significantly, but still left room for higher success rates, we reviewed our anomalous cases to determine whether a graduated adjustment might be expected to produce even higher success rates. A review of cases including additional ones since our last report failed to support this hypothesis. Satisfactory results in these most recent cases have, however, almost doubled the surgical success rate (in anomalous cases) for our stage I fixed arbitrary 1 mm intraoperative adjustment, from 47% to 90%.

Adolescent↗

PubMed1987

Microtubular protein impairment by pentanal and hexanal.

Pentanal and hexanal are some of the aldehydes produced by lipid peroxidation, that causes damage to several subcellular structures. Lipoperoxidation products may directly attack cytoskeleton structures, the integrity of which is required for secretion mechanisms, e.g. 4-hydroxy-alkenals after microtubular integrity and function. Purified microtubular protein incubated with pentanal and hexanal at different concentrations revealed a tubulin-aldehyde interaction affecting the polymerization reaction and the colchicine-binding activity. These reactions apparently do not involve sulphydryl groups, and the addition of mercaptoethanol does not protect microtubules from the action of aldehydes, the effect of which is however more homogeneous, as only small differences can be noticed among the various aldehyde concentrations used.

Aldehydes↗

PubMed1987

Some biological effects of calvatic acid and its analog on isolated hepatocytes.

Calvatic acid is a new antibiotic with both a carboxylic group and an azoxy function in the benzene ring. The relationship between structure and biological activity in this substance and one of its analog, phenylazoxyxyanide, was investigated. Isolated hepatocytes were used as an experimental system: the release of lactate dehydrogenase and the colchicine-binding activity of tubulin were first evaluated; effects were dose and time dependent. micromolar concentrations of these drugs determined a significant decrease of the glucose-6-phosphatase activity and a slight inhibition of aminopyrene demethylation. A toxic effect at the microsomal level and an interaction with the microtubular system are thus possible.

Aminopyrine N-Demethylase↗

PubMed1987