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Biomedical subjects

G Leroux

Publications and source records attributed to G Leroux.

At least 19 recordsLinked to original sources

The macrophage-specific membrane protein Nramp controlling natural resistance to infections in mice has homologues expressed in the root system of plants.

In mice, natural resistance or susceptibility to infection with Mycobacteria, Salmonella, and Leishmania is controlled by a gene named Bcg. Bcg regulates the capacity of macrophages to limit intracellular replication of the ingested parasites, and is believed to regulate a key bactericidal mechanism of this cell. Recently, we have cloned the Bcg gene and shown that it encodes a novel macrophage-specific membrane protein designated Nramp. A routine search of the public databases for sequences homologous to Nramp identified 3 expressed sequence tags (EST) that show strong similarities to the mammalian protein. We report the identification and cloning of a full-length cDNA clone corresponding to a plant homologue (OsNramp1) of mammalian Nramp. Predicted amino acid sequence of the plant protein indicates a remarkable degree of similarity (60% homology) with its mammalian counterpart, including identical number, position, and composition of transmembrane domains, glycosylation signals, and consensus transport motif, suggesting an identical overall secondary structure and membrane organization for the two proteins. This high degree of structural similarity indicates that the two proteins may be functionally related, possibly through a common mechanism of transport. RNA hybridization studies and RT-PCR analyses indicate that OsNramp1 mRNA is expressed primarily in roots and only at very low levels in leaves/stem. DNA hybridization studies indicate that OsNramp1 is not a single gene, but rather forms part of a novel gene family which has several members in all plants tested including cereals such as rice, wheat, and corn, and also in common weed species. The striking degree of conservation between the macrophage-specific mammalian Nramp and its OsNramp1 plant homologue is discussed with respect to possible implications in the metabolism of nitrate in both organisms.

Amino Acid Sequence

Cyclosporin A as a modifier agent in the salvage treatment of acute leukemia (AL).

Sixteen adult patients with relapsed (7 patients) or refractory (9 patients) acute leukemia received mitoxantrone (10 mg/m2 per day for 3 days) and etoposide (200 mg/m2 per day for 3 days) with escalating dose of cyclosporin A (CsA) from a loading dose of 2 mg to 6.5 mg/kg per 2 h followed by 3 days continuous infusion of 5-15 mg/kg per day. The major toxicities were stomatitis and prolonged aplasia, occurring for 15 mg/kg per day of CsA. Transient conjugated hyperbilirubinemia occurred in all patients, and was CsA dose-dependent (r = 0.7). Adequate serum levels of CsA (> 1 microgram/ml) were obtained in 3/6 patients treated with 10 mg/kg per day and 4/4 patients with 15 mg/kg per day. The pharmacokinetic of mitoxantrone showed an unusual increase of carboxylic metabolites, parallel to CsA levels. We observed six responses (two complete and four partial remissions), and eight resistances. Two patients died at days 3 and 8 from sepsis. Before treatment, 7/16 patients tested for P-gp with C219 were positive (> 10% positive cells). 3/6 responders were P-gp-positive. At time of leukemic regrowth, cells expressing P-gp before therapy reverted to P-gp-negative cells.

ATP Binding Cassette Transporter, Subfamily B, Mem

Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging.

Both the amygdala and the hippocampus are involved in the pathogenesis of a number of neurologic conditions, including temporal lobe epilepsy, postanoxic amnesia, and Alzheimer's disease. To enhance the investigation and management of patients with these disorders, we developed a protocol to measure the volumes of the amygdala and as much of the hippocampus as possible (approximately 90 to 95%) using high-resolution MRI. We present the anatomic basis of these two protocols and our results in normal control subjects. These volumetric studies of the amygdala may clarify the role of this structure in the pathogenesis of temporal lobe epilepsy.

Adult

Magnetic resonance imaging stereotaxy: recognition and utilization of the commissures.

Magnetic Resonance Imaging (MRI) offers a non-invasive method to visualize the intracerebral structures. Coupled to a compatible stereotactic frame and software, MRI can be used to determine the coordinates of intracranial targets. Coordinates of the anterior commissure, posterior commissure, targets and intercommissural distance were obtained from positive contrast ventriculography and by MRI in 6 patients undergoing stereotactic localization prior to the implantation of stimulating thalamic electrodes for pain control. The correlation of coordinates and measurements obtained with ventriculography and MRI is +/- 1 mm in most measurements, but up to 3 mm in 2 cases. Magnetic resonance stereotaxy allows non-invasive and precise localization of intracerebral targets, but does not yet allow its routine use with confidence. Further understanding of distortion and artifacts and corrections of these is mandatory.

Brain

[Chemiluminescence of phagocytic cells in chronic gingivitis and adult periodontitis].

Measurement of chemiluminescence (CL) produced by phagocytic cells spontaneously or upon stimulation by phorbol myristate acetate (PMA) was performed in patients with gingivitis and adult periodontitis, and in control healthy subjects. The study was performed simultaneously on phagocytic cells obtained from peripheral blood and from gingival blood, and on crevicular leukocytes. An elevated CL production was obtained in quiescent and PMA-stimulated phagocytic cells from peripheral blood in patients with gingivitis or periodontitis compared to non-diseased controls. Chemiluminescence produced by unstimulated crevicular phagocytes was similar to that of peripheral blood phagocytes in normal subjects, but it was decreased in periodontitis. Upon PMA stimulation, the CL response of crevicular phagocytes remained low in the three groups of subjects.

Adult

Cell-marker studies in CLL with monoclonal OKT antisera and lactic dehydrogenase isoenzyme analysis.

In 16 patients with B-type CLL, the T and B cell compartment was analysed using the monoclonal anti-T-cell antisera OKT1, 3, 4 and 8 and the lactic dehydrogenase enzyme marker. Pertinent findings were: the presence on the CLL cells in 15 out of 16 patients of the antigen determined by the OKT1 antiserum, and, in all patients, a lower total LDH content on a per cell basis combined with a higher percentage-activity in the LDH-3 band as compared to the normal B-cell. Furthermore, the T-cell compartment was also disturbed in these patients, as the ratio of OKT4+ to OKT8+ cells was significantly depressed accompanied by a significant decrease of the LDH-1 percentage-activity in favour of LDH-3 and 4. These findings argue for the B-cell being immature and confirm the recent evidence that the T-cell compartment is changed in B-CLL.

Antibodies, Monoclonal

[Immediate cardiac toxicity of rubidazone. A case reversible by isoproterenol].

It is reported the first observation of cardiogenic shock without delay, in a leukemic patient during a first injection of Rubidazone (22050 RP) which is recognized so far, as one of the least cardiotoxic anthracyclines. It has been concluded: --anthracyclines, beside the risk of a progressive cardiomyopathy which is related to the dose and very well known, can induce immediate cardiac injuries, which cannot be predicted yet; --the perfect myocardial protector is still to be discovered; --in this case, beta-adrenergic stimulators appeared to be able to control the cardiotoxic effect of Rubidazone; --the last fact could be considered in the decision to maintain the treatment when such an injury occurs during a chemotherapy or when it seems absolutely necessary to use such a drug.

Antibiotics, Antineoplastic

[Bronchogenic cysts. A clinical and regional lung function study before and after surgery (author's transl)].

Studies of regional lung function were performed on two children with bronchogenic cysts before and after surgery. The first patients, aged two, presented with a severe and continuous airflow obstruction leading to significant disturbance of perfusion per unit of alveolar volume; the abnormalities of perfusion were partly reversible when the ventilation was restored after surgery. Patient no 2, aged 10 years, had a voluminous peripheral cyst, which was shown to be ventilated by pulmonary function studies and further confirmed by bronchography. After lobectomy, studies revealed a reduction in the functional pulmonary parenchyma in the right hemithorax. The abnormal distribution of perfusion was still seen two years after the operation.

Adult

Large ventricular aneurysms occurring after myocardial infarction.

We have studied 33 patients with a large ventricular aneurysm complicating an anterior myocardial infarction. The features of myocardial infarction progressing towards an aneurysm were no previous history of coronary disease, severe infarction as shown by the severity of pain and the presence of pericardial rub and heart failure, and large increase in serum levels of cardiac enzymes. A large aneurysm usually follows a large infarction resulting from the total or partial occlusion of the left anterior descending artery, which is involved alone in about half the patients and is associated with lesions of the circumflex and right coronary arteries in the other half. In most cases, standard radiography showed an abnormal cardiac configuration, but in 7 patients (21%) there was no radiological evidence of aneurysm. ST segment elevation (mean 2.7 mm) was reported in all subjects but one. Heart failure was present in most patients and was an indication for surgical treatment in one-third of the patients. A large aneurysm was not a contraindication to operation even when at angiography the aneurysm seemed to occupy almost all the left ventricle. Twenty-one patients were operated upon for resection of the aneurysm with a mortality rate of 14 per cent.

Adult