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Biomedical subjects

L Gabriel

Publications and source records attributed to L Gabriel.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Methylglyoxal-tubulin interaction: studies on the aldehyde effects on hepatoma, liver and purified microtubular protein.

Methylglyoxal antiproliferative action is well known; this action may be exerted by a non-enzymic mechanism and may directly involve the microtubular system. Our purpose was to verify this hypothesis, by studying the aldehyde effect on normal and tumour microtubular protein. Methylglyoxal incubation of normal and tumour liver cell homogenates causes inhibition of colchicine binding activity above all at higher concentrations. The aldehyde administration to the purified microtubular protein induces alterations in some tubulin properties already at lower concentrations. These results show a possible tubulin-methylglyoxal interaction, also if the reaction mechanism is so far unclear.

Aldehydes↗

4-Hydroxy-alkenals interaction with purified microtubular protein.

4-Hydroxy-alkenals effect on microtubular system has been investigated, comparing the activity of both biogenic and non-biogenic aldehydes. As these aldehydes react essentially with sulphydryl groups, their action on titratable thiol groups microtubular protein was studied. These compounds evidenced an inhibitory effect on this parameter and on tubulin polymerization, where sulphydryls are essential. 4-Hydroxy-alkenals inhibit tubulin polymerization in a dose-dependent manner (0.1-1 mM), with the exception of 4-hydroxy-octenal, that shows an inhibitory action only in concentrations from 0.5 mM up. Its behaviour is very anomalous: in fact the tubulin-colchicine binding, is stimulated rather than inhibited, whereas such binding is inhibited by the other tested aldehydes. Our present results give then a support for an interaction between 4-hydroxy-alkenals and microtubular protein.

Aldehydes↗

Intraoperative adjustment of eye muscle surgery. Correction based on eye position during general anesthesia.

During general anesthesia, the eye position of patients with strabismus, measured by Krimsky's test at 1 m, 30 minutes after induction, has a linear correlation with the eye position measured clinically preoperatively. A similar study was performed on 77 patients; however, Hirschberg's test was used for simplicity and was performed as soon as the patient was in a surgical plane of anesthesia. We confirmed that there was a linear correlation. We also adjusted the surgery performed in seven cases where the test was anomalous, ie, when the eye position under anesthesia was more than 15 prism diopters more or less than expected based on preoperative clinical measurements. We did approximately 1 mm more or less surgery than we had planned on each eye muscle. This significantly improved the final results in anomalous cases. Patients with anomalous tests who did not have such adjustments had significantly poorer results.

Adolescent↗

Multiple myeloma with crystalline inclusions in most hemopoietic cells.

Intracytoplasmic inclusions were observed at light and electron microscopy in the cells of most of the hemopoietic series, including erythroblasts, in a case of multiple myeloma IgG kappa. The inclusions were of crystalline nature, surrounded by smooth membrane. An indirect immunoperoxidase method on thick sections confirmed their immunoglobulin G kappa nature. The fact that crystals were observed in various hemopoietic series suggests that, except for the plasma cells, their presence is more likely due to phagocytosis than to synthesis and, therefore, that they are not a clone marker.

Aged↗

Effect of methylglyoxal on tumour microtubular protein.

Methylglyoxal inhibits cell division, exerting an antiproliferative action on tumour cells. Supernatants from ascites hepatoma cell homogenate, previously incubated with the aldehyde, showed a decrease in colchicine binding activity dependent on methylglyoxal concentration. In contrast, in vivo treatment of tumour-bearing rats apparently did not cause a significant impairment of microtubular protein, suggesting that the aldehyde interaction with microtubules cannot be considered responsible for its carcinostatic action.

Aldehydes↗