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Biomedical subjects

B Schott

Publications and source records attributed to B Schott.

At least 19 recordsLinked to original sources
PubMed1992

P-glycoprotein overexpression cannot explain the complete doxorubicin-resistance phenotype in rat glioblastoma cell lines.

We have associated pharmacological studies to a semi-quantitative evaluation of P-glycoprotein(s) expression, to establish if classical multidrug resistance (MDR) could account for the complete resistance phenotype exhibited by progressively doxorubicin-resistant rat glioblastoma cells. Three resistant variants (C6 0.001, C6 0.1 and C6 0.5) of the C6 glioblastoma cell line (C6 S) were selected by long-term culture in the presence of three concentrations of doxorubicin (0.001, 0.1 and 0.5 microgram.ml-1 respectively). The degree of doxorubicin resistance was respectively 7, 33 and 400, and all the cell variants were cross-resistant to m-AMSA, etoposide and vincristine. Doxorubicin incorporation was reduced similarly in all resistant cells, irrespective of the level of resistance. When exposed to their respective doxorubicin IC50, the 7-fold resistant cells had the same intracellular drug incorporation as the sensitive cells, whereas the 33-fold and 400-fold resistant cells could incorporate respectively 3.7 and 17 times more drug. The ratio of doxorubicin exposures required for 50% DNA synthesis inhibition and 50% growth inhibition was dependent on the degree of resistance; this ratio was 12.8 in C6 S, 11.6 in C6 0.001, 6.3 in C6 0.1 and 1.8 in C6 0.5. P-glycoprotein(s) overexpression was of the same magnitude as the resistance factor in variants C6 0.001 and C6 0.1, but was lower than resistance factor in variant C6 0.5. Reversal of drug incorporation by verapamil was complete in all resistant cell lines; however, reversal of doxorubicin cytotoxicity was complete only in the 7-fold resistant line and was only partial in the most resistant lines, which remained 10-fold and 20-fold resistant to doxorubicin. These results suggest that classical MDR was the first phenotype selected by doxorubicin in C6 0.001, whereas mechanism(s) of doxorubicin resistance other than classical MDR are added in the most resistant lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Cellular pharmacology of 4'-iodo-4'-deoxydoxorubicin.

We have studied the growth inhibition, DNA synthesis inhibition and cell incorporation of the new anthracycline 4'-iodo-4'-deoxydoxorubicin (4'-iododoxorubicin) and of its 13-dihydroderivative in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells; results were compared to those obtained with doxorubicin and doxorubicinol in the same model. 4'-Iododoxorubicin was 7.5 times more potent than doxorubicin on the wild cell line and 45 times on the doxorubicin-resistant line, indicating that cross-resistance was only partial between the two drugs. Whereas doxorubicinol presented only a very faint cytotoxic activity, 4'-iododoxorubicinol retained the same activity as the parent drug against sensitive cells and a lower activity against resistant cells. DNA synthesis inhibition occurred for much higher doses than growth inhibition in the sensitive cells, but for similar doses in resistant cells. In both cell lines, 4'-iododoxorubicin and its metabolite were incorporated to a higher extent than doxorubicin and doxorubicinol respectively. Incorporation of metabolites was always lower than that of their parent compound. We have studied the metabolism of doxorubicin and 4'-iododoxorubicin by sensitive and resistant cells; only traces (less than 5%) of metabolites were identified in the cells as well as in the culture medium. A new cell line was selected for resistance in the presence of low amounts of 4'-iododoxorubicin. It presented a 6-fold resistance to 4'-iododoxorubicin and an 85-fold resistance to doxorubicin. Doxorubicin incorporation was markedly reduced in this cell line while 4'-iododoxorubicin was incorporated to the same extent as in the sensitive line. Measurements of drug efflux were performed in the three cell lines. No significant difference was exhibited between the efflux of doxorubicin and that of 4'-iododoxorubicin in each cell line; these effluxes were very rapid in the doxorubicin-selected resistant line, slow in the wild line and intermediate in the 4'-iododoxorubicin-selected line.

Animals↗
PubMed1990

[Left ventricular diastolic function in hypertensive heart diseases. Comparison of results obtained by echocardiography and mechanocardiography].

Usefulness of computerized mechanocardiography and echocardiography in the bedside diagnosis of impaired left ventricular diastolic function is established in a study comparing 17 hypertensive cardiomyopathy patients and 17 hypertrophic obstructive patients to 20 control. The echocardiographic study involves the ratio A/E obtained from the diastolic motion of the mitral valve and max DD/dtN, the peak rate of maximal diastolic dimension change. Both measurements allow statistical differentiation between pathological conditions and the control. The mechanocardiographic evaluation of left ventricular diastolic function provides easily three different parameters of diastolic function: isovolumic relaxation by the interval B2 alpha-0 or by t-dr/dt and the ratio dr/dt/A2, left ventricular stiffness by the A/H ratio and TRR the time of rapid filling. The mechanocardiographic indices allow clear distinction between the control group and the hypertrophic conditions for all the measured parameters giving evidence for an increased isovolumic relaxation period with a reduced velocity of relaxation, an increase in left ventricular stiffness and in the case of the hypertrophic obstructive cardiomyopathy, a prolonged time of rapid filling.

Adult↗
PubMed1990

[Disorders of voluntary motor activity and lesions of caudate nuclei].

Three clinical cases are reported, resulting in apathy, uninterest, flattened affect and lack of initiative for usual daily activities. Intellectual performances were normal and there was no depression. This syndrome was reversible when patients were stimulated. Stereotyped behaviors resembling compulsions were frequent. One of the patients presented with prolonged akinetic episodes reversible by verbal stimulation. CT and MRI showed bilateral lesions, mainly in and around the head of the caudate nucleus. Such behavioral disorders have been termed psychic akinesia or athymhormia syndrome, suggesting that the patients suffered from a loss of drive and motivation. The lesions involved bilaterally the globus pallidus, the striatum or the frontal lobe. Recently, anatomical findings have shown several circuits through the basal ganglia additional to the motor circuit. The caudate nucleus receives inputs from the prefrontal and limbic cortex. These inputs are transmitted to the globus pallidus, then to the thalamus and ultimately return to the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate areas. Lesions in any part of these cortico-subcortical loops may be responsible for a dramatic behavioral syndrome, emphasizing their functional specificity in drive. However, a procedural learning impairment in neostriatal dysfunction could possibly explain the disorders observed in our patients.

Brain Diseases↗
PubMed1990

[Cortical pain. Clinical, electrophysiologic and topographic study of 12 cases].

Vascular lesions of the cerebral cortex sparing the thalamus (MRI or CT with reconstructions) may be accompanied by burning or constrictive pain which suggests thalamic pain as it affects one half of the body and is associated with induced pain. Summation hyperpathia is rare; allodynia is more common and sometimes isolated (2 cases). Cortical pain may be paroxysmal, and in 3 of our patients it progressed like a jacksonian seizure. The territory of pain is also the site of global or spinothalamic hypoaesthesia (5 cases). Early SEPs are abolished or of low amplitude (8 cases). The lesion is located in area SI or extends to the thalamo-parietal radiations; in 11 out of 12 patients it was located in the minor hemisphere. Two physiopathological theories are discussed: hyperactivity of the intralaminar thalamus relieved from cortical inhibition, or denervation hyperactivity related to the cortical or subcortical lesion.

Adult↗
PubMed1990

Mechanocardiographic evaluation of left ventricular diastolic function in hypertrophic cardiomyopathy and hypertensive cardiomyopathy.

Usefulness of computerized mechanocardiography and echocardiography in the diagnosis of impaired left ventricular diastolic function is shown in a study comparing 17 hypertrophic obstructive cardiomyopathy and 17 hypertensive cardiomyopathy patients to 20 normal subjects. Mechanocardiography allows the evaluation of three different parameters of diastolic function: isovolumic relaxation evaluated by S2a-O or better by t-dr/dt and dr/dt/A2 ratio, left ventricular compliance by the A/H ratio and time of rapid filling. All the parameters are impaired in both pathological populations. Isovolumic relaxation being more depressed in hypertensive cardiomyopathy and duration of rapid filling being prolonged especially in the hypertrophic obstructive cardiomyopathy patients. Although the differences are small indicating only trends computerized mechanocardiography gives some evidence for difference in the alteration of diastolic function in hypertrophic obstructive cardiomyopathy and hypertensive cardiomyopathy.

Cardiomyopathy, Hypertrophic↗
PubMed1989

Comparative activity of anthracycline 13-dihydrometabolites against rat glioblastoma cells in culture.

We have studied the growth inhibition, DNA synthesis inhibition and cell incorporation of five 13-dihydrometabolites of anthracyclines in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells. These compounds were major metabolites for doxorubicin, epirubicin, daunorubicin, idarubicin and the new anthracycline 4'-deoxy-4'-iododoxorubicin and are known to be present in appreciable amounts in the plasma of patients treated with these drugs. We have shown that in vitro growth inhibition in sensitive cells was either much lower than that of the parent drug (doxorubicinol, epirubicinol, daunorubicinol), or similar to it (idarubicinol, 4'-iodoxorubicinol). In resistant cells, growth inhibition was about 100 times lower than in wild cells, and was always lower than that of the parent anthracycline. DNA synthesis inhibition occurred in sensitive cells for doses about 100 times higher than those required for growth inhibition, but in resistant cells, similar doses provided growth inhibition and DNA synthesis inhibition. Metabolite incorporation was always lower than that of the corresponding parent anthracycline; it was greatly reduced in resistant cells as compared to sensitive ones. The calculated intracellular concentrations obtained for the same growth inhibition are higher in resistant cells than in sensitive cells; in contrast, the calculated intracellular concentrations obtained for the same DNA synthesis inhibition are similar in resistant and sensitive cells, and similar for all the metabolites studied. These results suggest that the amount of drug incorporated is primarily responsible for DNA synthesis inhibition, which is directly correlated to growth inhibition in resistant cells, but not in sensitive cells.

Animals↗
PubMed1989

Comparative cytotoxicity, DNA synthesis inhibition and drug incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat glioblastoma cells.

We have compared the growth inhibition, DNA synthesis inhibition and cell incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells. The anthracyclines studied were both the reference molecules (daunorubicin, doxorubicin) and the new drugs recently introduced in clinical use or in trials (epirubicin, idarubicin, pirarubicin, esorubicin, rubidazone, 4'-deoxy-4'-iododoxorubicin). We have shown that the in vitro growth inhibition was correlated with the LD50. The new anthracyclines were more potent than the reference drugs in the sensitive cells and the resistance patterns revealed a reduced cross resistance of idarubicin, pirarubicin and 4'-deoxy-4'-iododoxorubicin towards the doxorubicin-resistant line. DNA synthesis inhibition occurred for much higher doses than growth inhibition in sensitive cells, but for similar doses in resistant cells. This suggests that different mechanisms could be involved in the mechanism of growth inhibition in sensitive and resistant cells. For similar exposures, reduction of drug incorporation was a general feature in the resistant line when compared to the sensitive one. However, no correlation was shown, for the various drugs, between the reduction of incorporation and the resistance factor. Moreover, the intracellular concentration required for growth inhibition is much higher in resistant cells than in sensitive cells, suggesting that increased drug efflux might not be the only mechanism to explain drug resistance.

Animals↗
PubMed1989

[Lexical agraphia caused by left temporoparietal hematoma].

A patient presented with dysorthographia associated with amnestic aphasia due to a left temporo-parietal hematoma. Reading, copying, graphism of letters were normal. Dictation showed better results for logatomes and regular words, without orthographical difficulty, than for those with orthographical problems (ambiguous and irregular words). The overall features suggested a disorder of the lexical system in which orthography of words known to patients is present. The phonological pathway of phoneme-grapheme conversion was preserved since errors were usually phonologically correct. Initially it was possible to conclude to a disorder of the semantic value of words in their visual form. Oral spelling, auditory reading and written denomination also showed more errors for words of difficult orthography. This patient presented a disorder of visual representation of words. Comparison of this case with the few reported ones showed that the latter often had amnestic aphasia and differed from our case in the associated lexical or phonologic alexia. A common feature of the lesions is involvement of the left angular gyrus is right-handed patients.

Aged↗
PubMed1987

[Early somesthetic evoked potentials and sensory deficits in thalamic and juxta-thalamic lesions. Clinical, electrophysiological and x-ray computed tomographic study in 70 patients].

Somatosensory Evoked Potentials (SEPs) have been recorded in 70 patients presenting a thalamic or capsular CT scan lesion. The loss of SEP parietal components confirmed the deafferentation of somatosensory cortex in infarctions of geniculothalamic or anterior choroidian arteries territory. SEPs were found to be normal in infarctions of other arterial territories, in agreement with the clinical evidence of normal somatosensory performances. In patients with haematomas, especially when located in the thalamus, there was no clear correlation between lesion sites and SEP data. Abnormal parietal responses were always associated to impaired tactile and joint sensations. The correlation was less significant for vibration sense. In four cases of selective loss of pain sensation SEPs were normal. In seven patients with abnormal parietal responses sterognosis was normal, a situation which is never encountered in cortical lesions. SEPs reliably documented the degree of somatosensory loss in patients with tactile extinction phenomenon. Contralateral parietal responses were reduced in four patients with tactile extinction but no attentional deficit for other sensory modalities. Thus normal SEPs are a prerequisite to consider thalamic neglect syndrome as a pure attentional disorder. Moreover SEPs demonstrated that there was no long-lasting deafferentation of somatosensory cortex in ataxic hemiparesis. It was found that selective loss of post-or prerolandic SEP components could occur in capsular lesions. This finding favors the hypothesis of parallel and independant thalamo-parietal and thalamo-frontal somatosensory projections that may be selectively damaged in lesions of thalamocortical radiations.

Adolescent↗
PubMed1986

Cerebrospinal fluid and serum immune complex in acute inflammatory polyneuritis. Detection by Clq binding assay.

Immune complexes (IC) were assessed in serum and CSF from 11 patients with acute inflammatory polyneuritis (AIP). An 125 I-labeled Clq binding assay (Clq BA) was used. IC were present in the sera of four patients and in the CSF of six. CSF-Clq BA of AIP (Group 1) were compared with 12 patients with other inflammatory neurological diseases (Group 2) and 22 patients with non-inflammatory neurological diseases (Group 3). There was only a significant difference between Group 1 compared to Group 3 (p less than 0.05). Serum and CSF IC did not correlate either with blood-brain barrier lesions or with immunoglobulin deposits in sural nerve biopsy.

Acute Disease↗
PubMed1986

[Thalamic pain: critical study of 43 cases].

Apart from hyperpathia, which is an entity in itself, thalamic pain presents a clinical spectrum of variable quality and intensity that justifies the description of "thalamic pains". Their mechanisms can be related to two basic mechanisms. The first involves the dependence of the thalamus to the afferent spinothalamic system. A lesion of the lemniscal system resulting from lesions of the thalamic sensory nuclei--capable of provoking a syndrome of paresthesia-hyperpathia (P-HI)--provokes a loss of gate control normally ensured by this discriminatory system and thus releases the pathologic nociceptive reactivity. Some authors think that the thalamic lesion alters the activity of control of the VPL nucleus on the lumbosacral spinothalamic tract. This concept considers thalamic pain as identical with brain stem spinothalamic pain provoked by exclusion of the control system arising in the giant-cell reticular nucleus and projecting onto onto the posterior horns. However, most cases of thalamic pain appear to be dependent on another mechanism involving the thalamocortical loop. In this case the thalamic sensory nucleus lesion is involved insofar as it implicates the reciprocal thalamocortical connections and the reticular nucleus. Involvement of the Th-C-Th loop as the ultimate representative of the lemniscal gate control is supported by "pseudo-thalamic" pains related to cortico-subcortical lesions with abolished SEP. But the numerous cases of painful thalamic syndromes with lemniscal sparing and normal SEP lead to incriminate a lesion of a specific thalamocortical control system for pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1985

[Lymphocyte subpopulations of the blood and cerebrospinal fluid in acute polyradiculoneuritis. Study of 14 cases using monoclonal antibodies].

The T lymphocytes in blood and CSF of 14 patients with acute polyradiculoneuritis were studied using the OKT series of monoclonal antibodies. Results were compared with findings in two control groups. Three patients with cytomegalovirus infection showed elevation of circulating OKT 8. A significant increase in the mean ratio OKT 4/OKT 8 was noted in all other cases, corresponding in 4 of the 11 patients to a reduction in number of OKT 8 lymphocytes. The CSF was normal in 3 of the 14 cases.

Acute Disease↗
PubMed1985

[Familial paroxysmal ataxia sensitive to acetazolamide. 3 cases in a new European family].

UNLABELLED: This family is the tenth reported world-wide and the second reported in Europe. Two of 3 brothers, their mother and probably their maternal grandmother were affected. CLINICAL FEATURES: paroxysmal bouts of ataxia and dysarthria, nystagmus of permanent gaze, the dominant autosomal transmission, the benign nature of the affection and the remarkable efficacy of acetazolamide were typical of familial paroxysmal ataxia. Specific points emphasized are the presence of a mild pyramidal syndrome as a permanent finding in 2 of these patients, and the anomalies of visual (longer lag period) and somesthetic (slowed conduction rate in the lemniscus medialis) evoked potentials probably the result of extension into other pathways than the cerebellar system. The finding of some degree of glucose intolerance, noted previously (Aimard, Vighetto et al., 1983) raises the question of the place of this disease in the group of paroxysmal ataxias due to pyruvic metabolism disorders.

Acetazolamide↗
PubMed1984

[Treatment of morning migraine. Clinical and biokinetic correlation of programmed-release dihydroergotamine].

The authors have tested a new preparation of dihydroergotamine (microgranules in a capsule) by comparing the clinical results obtained in 30 patients suffering from morning migraine with the plasma levels of the active substance measured in 8 healthy subjects. The microgranules were administered in doses of 30 mg/24 hours and compared with a similar dose of a dihydroergotamine solution. The close correlation observed between sustained plasma levels and prolonged therapeutic effects indicates a truly programmed delivery of dihydroergotamine by the microgranule preparation.

Adolescent↗
PubMed1984

A chronobiological study of melatonin, cortisol growth hormone and prolactin secretion in cluster headache.

The temporal organization of plasma melatonin, cortisol, growth hormone (GH) and prolactin secretion was examined in healthy rested controls and in patients suffering from episodic cluster headache. Eleven patients with typical cluster headache (10 men, 1 female) and 8 male controls were studied over a 24-h period: blood was collected at 2-h intervals during the day and at 1-h intervals at night. Plasma melatonin, cortisol, GH and prolactin levels were determined by radioimmunoassay. Most of the cluster headache patients showed a decrease in nocturnal melatonin secretion and the melatonin rhythm was even completely abolished in one patient. Chronobiological analysis of the cluster headache patients' 24-h plasma melatonin profile showed a significant decrease in amplitude and mesor: these were 58.7 pg/ml and 34.4 pg/ml respectively in control subjects, versus 18.7 pg/ml and 17.6 pg/ml for the patients. In addition, patients showed a significant phase-advance in their melatonin rhythm. For cortisol, the rhythm appeared slightly blunted in the cluster headache group and was significantly phase-advanced. The plasma prolactin profile showed no significant alteration, but for plasma GH the nocturnal peak was advanced in some patients; in the absence of sleep recording, however, no conclusion could be drawn. Results from this study suggest a neuroendocrine dysregulation in cluster headache in the endogenous clock which controls the pineal rhythmicity.

Adult↗