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Biomedical subjects

G Lazar

Publications and source records attributed to G Lazar.

52 records · Page 3Linked to original sources

Metabolic basis of endotoxicosis.

Whereas as specific immunological responses are elicited only after a delay of some days, alteration in various biochemical parameters is observed within 1-2 h of endotoxin administration in a number of animal species. Generally the level of several hepatic enzymes (tryptophan pyrrolase, phophoenol pyruvate carboxykinase) metabolites (glycogen, NAD) and intermediates in the energetic homeostasis is lowered by the toxin, increased by the glucocorticoid hormones and maintained at the normal level when the toxic effects of endotoxin are annulled by the counter effects of the protective agent (such as cortisone). Antagonism is also noted on the synthesis of cellular RNA, DNA and protein. However, no unitary process has as yet been singled out to possessing a cause and effect relationship between toxicity and survival. In the intact animal, it is not possible to affirm whether the toxin exerts a direct effect on the organ, the cell or the process in question, especially since endotoxin is phagocytized by the cells of the reticuloendothelial system (RES) in the liver and elsewhere and since the biochemical parameters are a property of the organ specific epithelial cells. Experiments with tissue slices suffer from the problem of permeability and uptake in vitro and are not readily reproducible. Isolated cells in culture are theoretically ideal but exhibit loss of functions and undergo neoplastic type of transformation that renders them unsuitable for relevant biochemical studies. Primary explants of the hepatocytes and the RE cells, as well as hybrids between these two cellular types appear more promising. However, at the moment, isolated liver preparations perfused in vitro offer the best solution by exhibiting intact function, morphology and excellent reproducibility. Collectively, it is tempting to speculate that the extent of subsequent immunological response is a reflection of the preceding biochemical processing, that both sorts of events are in some way mediated by the RE cells, and that the latter may most easily be studied in the intact liver in vitro.

Animals↗

An investigation into the hypothesis of shifting neuronal relationships during development.

The projection of ganglion cells from the centre of the eye to the tectum has been followed during development in Xenopus by an autoradiographic technique. By comparing the caudal limit of this projection with a fixed line of cells labelled with tritiated thymidine the projection has been shown to shift caudally during development. This indicates a less rigid form of neuronal specificity than has previously been accepted.

Animals↗

Antimineralocorticoids.

A number of chemical modifications in the spironolactone molecule were attempted over the last decade to synthesize ligands with high affinity for the mineralocorticoid receptor (MCR), and for possible use in the clinical control of the hypertensive disease. ZK 91587 has been commercialized as the 'ideal' ligand for the MCR, replacing the natural hormone aldosterone. None of the derivatives was retained for possible clinical use as an improvement over Canrenone or Spironolactone. No apparent correlation could be drawn between affinity for the MCR in vitro and biological potency in vivo. Such considerations challenge classical notions regarding the receptor mediated hormone action.

Animals↗

[Microdeletion 22q11: apropos of case of schizophrenia in an adolescent].

Deletion of chromosome 22q11 concerns nearly 1/5.000 births, and is the most frequent interstitial microdeletion. The deletion generates various phenotypes which were initially regarded as distinct syndromes. 1) Di George syndrome was described in 1962 by immunologists, and associates thymic and parathyroid hypoplasia, cardiac malformation, and dysmorphic face; the prognosis is severe, as Di George syndrome is a life-threatening condition. 2) The velocardiofacial syndrome was described in 1978 by stomatologists, and associates palate abnormalities, cardiac malformations, dysmorphic faces, and learning disabilities. 3) The Takao syndrome was described in the late seventies by cardiologists as a clinical condition associating cardiac abnormalities and dysmorphic faces. During the nineties, a common molecular etiology was identified, and a new name proposed: CATCH 22, an acronyme for Cardiac abnormalities, Abnormal face, Thymic hypoplasia, Cleft palate, Hypocalcemia, deleted chromosome 22. Furthermore, new phenotypes have been recently recognized, most of them belonging to the psychiatric spectrum. Descriptive studies of large samples of children with 22q11 deletion, conducted, both in the United States and european countries, have shown the following pattern of associated symptoms:--abnormal face (100%), which expression varies with age, and can be discrete;--cardiac abnormalities (84%), including cardiac malformations of conotroncal types;--mouth abnormalities (49%), including cleft palate (14%), and velar dysfunction (20%);--urinary tract abnormalities (36%), including ureteric reflux, lung dysplasia;--transitory hypocalcemia (60%) mostly during infancy, and due to transitory hypoparathyroid dysfunction;--seizures (21%), which are usually a consequence of hypocalcemia;--immunodeficiency (1%), which worsens the prognosis. Deletion of chromosome 22q11 has been also associated with various psychiatric phenotypes, which can be classified into two groups, developmental abnormalities and psychiatric conditions. The great majority of patients with the deletion exhibit impairment of language and motor development, mild mental retardation, persistent coordination deficits, and poor academic performance. The deletion of chromosome 22q11 is also associated with high frequency of behavioral disorder with attention deficit during childhood, and with high frequency of psychotic disorder (bipolar disorder, and schizophrenia) during adolescence and young adulthood. The link between the 22q11 deletion and schizophrenia has been also supported by recent studies showing that the rate of 22q11 deletion in adults with schizophrenia (2%) is higher than it is in the general population. The rate may even be higher (6%) in subjects with childhood onset schizophrenia. The present work reviews the psychiatric literature associated with 22q11 deletion. We also report a case of 22q11 deletion in a 17-year-old girl that was initially diagnosed as paranoid schizophrenia. We will discuss the diagnostic, prognostic, and therapeutic consequences that such a genetic diagnosis implies. In the case reported here, transitory hypocalcemia induced: 1) dystonic symptoms that was believed to be catatonic symptoms or neuroleptic secondary effects, by clinicians; 2) a poor response to neuroleptic medication.

Adolescent↗