Effect of interfacial octahedral behavior in ultrathin manganite films.

We investigate structural coupling of the MnO6 octahedra across a film/substrate interface and the resultant changes of the physical properties of ultrathin La2/3Sr1/3MnO3 (LSMO) films. In order to isolate the effect of interfacial MnO6 octahedral behavior from that of epitaxial strain, LSMO films are grown on substrates with different symmetry and similar lattice parameters. Ultrathin LSMO films show an increased magnetization and electrical conductivity on cubic (LaAlO3)0.3(Sr2AlTaO6)0.7 (LSAT) compared to those grown on orthorhombic NdGaO3 (NGO) substrates, an effect that subsides as the thickness of the films is increased. This study demonstrates that interfacial structural coupling can play a critical role in the functional properties of oxide heterostructures.

Genetic determinants of cutaneous malignant melanoma in Sinclair swine.

The role of genetic factors involved in the determination of risk of cutaneous malignant melanoma (CMM) in humans remains unclear owing to genetic heterogeneity and reliance on simplistic models of inheritance. Here, we report a statistical genetic analysis of cutaneous malignant melanoma in Sinclair swine (SSCM), a unique animal model for human CMM. Using complex segregation analysis a two-locus model involving an unknown major locus and a second locus that lies within or close to the swine leukocyte antigen (SLA) complex jointly determine risk of SSCM in pedigreed animals. These loci also influence severity of affection, accounting for approximately 20% of the phenotypic variation in quantitative tumour burden.

Common swine leucocyte antigen (SLA) haplotypes in NIH and Sinclair miniature swine have similar effects on the expression of an inherited melanoma.

Mixed lymphocyte culture and serological typing of NIH and Sinclair miniature swine indicate that the two herds share a common SLA haplotype. NIH haplotype a (International Haplotype H10) appears identical to Sinclair haplotype B, which has significant effects on the penetrance of Sinclair swine cutaneous malignant melanoma (SSCM). Offspring of crosses between melanoma-bearing Sinclair swine homozygous for the B haplotype and non-melanoma NIH aa swine have tumour incidence identical to Sinclair melanoma BB x Sinclair non-melanoma BB offspring. Our results provide further support for the involvement of the swine leucocyte antigen (SLA) complex in the inheritance of SSCM, and identify a new source of non-tumour animals that have all of the genes for SSCM except those at the tumour-initiator locus.

Blood magnesium, potassium, sodium, calcium and cortisol in drug-free depressed patients.

Many biochemical variables, including plasma and erythrocyte magnesium, were simultaneously measured in drug-free depressed patients (n = 34), compared to healthy controls (n = 35). Higher plasma and erythrocyte magnesium concentrations were observed in patients than in controls (+12 per cent, P < 0.0001 and 14 per cent, P < 0.0001, respectively). In contrast, patients showed a lower plasma potassium level (-10 per cent; P < 0.007). Cortisol secretion was much higher in patients (+35 per cent; P < 0.02), particularly in females, showing overactivity of the hypothalamo-hypophyseo-adrenal axis in the patients. Except in a few cases, plasma sodium and calcium in patients did not differ from control values. Significant differences in magnesium and cortisol levels were observed between patients classified in diagnostic groups and by sex, whereas little variation in the other biochemical indices was noted. The increase in blood magnesaemia and its possible association with central hypocatecholaminergic deficiency in affective disorders are discussed.

Adrenaline-induced platelet aggregation in depressed patients and control subjects.

We measured alpha 2-adrenoceptor-mediated platelet primary aggregation in depressed patients and healthy subjects. Both initial velocity and maximum amplitudes of platelet response to increasing concentrations of adrenaline were decreased in drug-free depressed patients as compared with controls. The EC50 of both initial slope and maximum amplitude were also increased in drug-free depressed patients. The results suggested a lowered platelet alpha 2-adrenoceptor function. Demographic factors (age and sex) and the time between blood collection and start of aggregation monitoring did not influence the results. This report is consistent with postsynaptic receptor desensitization in depressed patients. The precise molecular mechanism for this impairment remains to be elucidated.

Platelet membrane alpha 2-adrenergic receptors in depression.

The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.

[Erythrocyte membrane transport of amino acid precursors of monoamines in schizophrenic patients. Comparison with depressive patients]. / Transports membranaires érythrocytaires des acides aminés précurseurs des monoamines chez les schizophrènes. Comparaison avec les dépressifs.

The study concerned 72 schizophrenic and 200 depressed patients hospitalised between 1983 and 1990. The erythrocyte membrane transports (EMT) of L-tyrosine and L-tryptophan (at 37 degrees, 0 degrees and 37-0 degrees) of schizophrenics without treatment nor depression were different compared to controls and depressed patients. The schizophrenics under neuroleptic treatment and/or depressed showed same means of EMT values as depressed patients. The slopes of the correlations between EMT of tyrosine or tryptophan at 37 degrees, 0 degrees and 37-0 degrees, as well as that between plasma levels of these amino acids, were parallel. However the slopes of the correlations between EMT of tyrosine and tryptophan were different according to the subgroups of patients: the perturbations of EMT were related to the clinical characteristics. In depressed patients and in schizophrenic patients under neuroleptic treatment and/or depressed, little changes in EMT of tyrosine were related to high changes of EMT of tryptophan.

Developing and implementing a "basic science clerkship" for first-year students.

For over 15 years, human genetics at the University of Illinois College of Medicine at Chicago (UICMC) was taught exclusively through lectures. In 1989-90 the authors revised this course for the graduating class of 1993 in order to incorporate many features found in a clerkship experience, such as oral presentations and the exploration of differential diagnoses through patient cases. In addition to lectures, the revised course consisted of small-group work in concentrated blocks of time, involving both a library research project and problem-based learning, each of which contributed to (1) significant gains in student achievement compared with data from the class of 1992 and (2) extremely favorable assessments from the students and faculty. The format of a basic science clerkship is being adopted by other departments at UICMC. The authors suggest that this format could be used by other medical schools to integrate the basic and clinical sciences.

Inherited congenital adrenal hyperplasia in the rabbit: absent cholesterol side-chain cleavage cytochrome P450 gene expression.

We investigated adrenal steroidogenic enzymes, their activity and mRNA expression, and in vitro biosynthesis of an enzyme in rabbits with congenital adrenal hyperplasia (CAH; weight: CAH, 19 +/- 5 mg/adrenal; normal, 2.7 +/- 1.0 mg/adrenal). Serum pregnenolone (delta 5-P) levels in CAH newborn rabbits (12-36 h) were normal (mean/range, 438/51-2191 ng/dl), but corticosterone levels were low [0.05 +/- 0.05 microgram/dl; P less than 0.001 vs. normal (0.66 +/- 0.57)]. Serum Na+ levels in CAH newborn rabbits were in the normal range (143 +/- 30 meq/liter), but K+ levels were elevated [7 +/- 1.1 meq/liter; P less than 0.05 vs. normal (5.9 +/- 0.6 meq/liter)]. Minced normal adrenal tissue incubated with [3H] cholesterol (30-100 pmol/flask) and ACTH (100 mU/flask) produced [3H]delta 5-P (newborn, 21 and 45 fmol/100 mg; adult, 3 and 5 fmol/100 mg) and [3H]corticosterone (newborn, 23 fmol/100 mg; adult, 11.3 fmol/100 mg), but CAH adrenals produced no product (less than 1.3 fmol/100 mg). Adrenal mitochondria from normal newborn rabbits produced delta 5-P (4.4-7 nmol/mg protein), but CAH adrenals did not, while CAH adrenal mitochondria demonstrated over 4 times greater 11 beta-hydroxylase activity. A Western blot of adrenal homogenate from normal newborn rabbits revealed a cholesterol side-chain cleavage cytochrome P450 (P450scc)-immunoreactive species (mol wt, 53 x 10(3), but this species was absent in CAH adrenals; CAH adrenals had a normal adrenodoxin and intensified 17 alpha-hydroxylase cytochrome P450 (P450(17)alpha) band compared to normal adrenals. In vitro translation of RNA in a cell-free rabbit reticulocyte lysate system containing [35S] methionine yielded a precursor P450scc protein (mol wt, 58.5 x 10(3)) with normal adrenal RNA, but not with CAH adrenal RNA. P450scc mRNA was detected in all normal adrenals, but was not detected in all CAH adrenals. 21-Hydroxylase cytochrome P450 mRNA expression was detected at a similar level in both normal and CAH adrenals. We conclude that CAH in the rabbit is caused by inherited absent P450scc gene expression. The clinical, pathological, and biochemical manifestations of P450scc deficiency in the rabbit are nearly identical to the human disorder. Increased 11 beta-hydroxylase activity and increased P450(17)alpha on Western blot of CAH adrenals indicate altered gene expression of other steroidogenic enzymes due to CAH. Further molecular analysis of the P450scc gene in this animal CAH model will facilitate understanding of P450scc deficiency CAH.

Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months.

No consensus has been obtained about blood electrolyte status, especially about magnesium, in affective disorders. This is mainly due to the lack of information about the distribution of the patients in clinical subgroups, sex, type of treatment and about the severity of their illnesses. Most of these studies concerned treated patients. We confirmed in this study that drug-free depressed patients have higher erythrocyte and plasma magnesium than controls, as shown in previous reports. Significant differences are observed in as shown in previous reports. Significant differences are observed in patients for sex and between clinical subgroups. Low plasma potassium levels are described in both male and female depressed patients. The erythrocyte magnesium level tends to normalize in parallel with clinical improvement, depending on sex and clinical subgroup, and seems then to be related to the intensity of the depression. Plasma magnesium in male and female patients, except for female unipolars, remains higher than controls in all conditions and might be related to the diagnosis of affective disorders.

Decrease in epinephrine-induced attenuation of platelet adenylate cyclase activity in depressed patients: relation with plasma electrolytes.

We have measured the alpha 2-adrenoceptor-mediated inhibition of platelet membrane adenylate cyclase in depressed patients and control subjects. The results showed a decrease in the forskolin-stimulated adenylate cyclase inhibition of depressed patients compared to the healthy subjects. This suggests a subsensitivity of alpha 2-adrenoceptor in depression. However, this subsensitivity was not correlated to the severity of depression as both severely and moderately depressed patients exhibited the same percent of adenylate cyclase inhibition. The antidepressant drugs treatment induced an increase in the percent of adenylate cyclase inhibition with a trend towards the control values. However, this increase did not equal control value, and moreover both remitted and unremitted patients presented a similar change in their alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. This result raises the question about a simple and direct relation between the clinical status of depression and the power of alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. Plasma magnesium and sodium yielded correlations to this alpha 2-adrenoceptor-mediated adenylate cyclase inhibition suggesting a relation between the platelet adrenergic function and plasma electrolytes.

[Plasma levels and membrane transports in red blood cell of tyrosine and tryptophane in depression. Evaluation at baseline and recovery]. / Taux plasmatiques et transports membranaires dans le globule rouge de la tyrosine et du tryptophane dans les états dépressifs. Evaluation en ligne de base et á l'euthymie.

The erythrocyte membrane transports (MT) of L-tyrosine and L-tryptophan, as well as their plasma levels, were measured in 143 depressed patients after a wash-out period of one week and before any antidepressant treatment, and then at regular intervals until they recovered. 49 normal subjects served as a control group. The perturbations of these biologic variables at baseline were different according to diagnostic groups (DSM III), compared to controls: significant decrease of the two MT in depressed bipolar disorders; significant decrease of MT in depressed bipolar disorders; significant decrease of MT tyrosine and significant increase of MT tryptophan in recurrent major depressions; no significant changes of MT in dysthymic disorders. The plasma levels of tyrosine and total tryptophan show a significant diminution in the 3 groups. The study of the evolution of these same variables after antidepressant treatment show a return to normal of the MT at recovery, as well as the plasma levels of tyrosine. The plasma levels of tryptophan stay low in depressed bipolar disorders and recurrent major depressions.

[Plasma MHPG, peripheral noradrenergic marker and hormonal plasma levels of cortisol-T3-T4-TSH in depressive syndromes]. / Contribution á l'étude du MHPG plasmatique marqueur noradrénergique périphérique et des taux plasmatiques hormonaux de cortisol-T3-T4-TSH dans les syndromes dépressifs.

Based on the hypocatecholaminergic hypothesis in the depressive syndromes, this survey on 30 depressed patients compared to 21 control patients, attempts to state exactly the potential interactions between the noradrenergic system and the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid neuroendocrine axis. The biological indices used during this survey are: total plasmatic MHPG, the basic plasmatic cortisol, the thyroid hormones T3, T4, free T4, and the TSH. The results of this survey reveal a significative increase of the basic plasmatic cortisol among the depressed patients, including dysthymics, a decrease of the plasmatic MHPG during major depressions, and a significant fall of the total T3 among depressed men, as well as some correlations between the different axes, the interpretation of which remains "ticklish".

Beta-adrenoceptor density of intact mononuclear leukocytes in subgroups of depressive disorders.

Binding parameters of (-)-iodopindolol to beta 2-adrenoceptors were determined on intact mononuclear cells in 41 untreated patients with different DSM-III subtypes of depression. Both maximal beta-receptor density (Bmax) and dissociation constant (Kd) were not significantly different between control and all depressed subjects. However, Bmax was significantly decreased in unipolar patients as compared to controls (p less than 0.001) whereas no significant difference was found in bipolar or dysthymic patients. In unipolar patients, a very strong association was found between Bmax values and the severity of the depression as assessed by the Hamilton Depression Rating Scale score (r = -0.75; p less than 0.005). This correlation was also highly significant in the entire depressed population (r = -0.58; p less than 0.0009). These results suggest that the lower number of beta-adrenoceptors in intact leukocyte cells of depressed patients is related to the depression severity.

[Erythrocyte membrane transports of monoamine precursor amino acids in schizophrenia]. / Transports membranaires érythrocytaires des acides aminés précurseurs des monoamines chez les schizophrènes.

We have determined the erythrocyte membrane uptake of the monoamine precursors L-tyrosine (L-TYR) and L-tryptophane (L-TRYP) in 72 patients with schizophrenia: 21 without neuroleptic treatment and not depressed, 15 with neuroleptic treatment and depressed, 33 without neuroleptic treatment, 27 depressed, compared to: 59 control subjects, and 54 depressed patients. We found that the ratio of L-TYR facilitated membrane diffusion to that of L-TRYP is: decreased when the patients are depressed, increased when they are untreated. When untreated patients receive neuroleptics and are depressed, the ratio tends to equal that of depressed patients'. The meaning of these anomalies is analysed, using our up-to-date knowledge of the erythrocytes's role in uptaking and dispatching the human body amino-acids, and of the role of these uptakes in regulating the functional monoamine balance. We postulate that in depressions, Parkinson's disease and schizophrenia, a change of membrane fluidity occurs, being decreased in depressions and Parkinsons's disease, and increased in schizophrenia.

Early decrease in density of mononuclear leukocyte beta-adrenoceptors in depressed patients following amineptine treatment: possible relation to clinical efficiency.

1. The effect of chronic amineptine treatment (200mg/day) on beta-adrenoceptor density of intact mononuclear leukocytes (MNL) was examined in unmedicated major unipolar depressed patients. 2. Pretreatment parameters of (-)-[125I]-iodopindolol specific binding did not differ significantly from age- and sex-matched healthy controls as the patients were only moderately depressed. 3. All patients showed a highly significant clinical improvement as assessed by the AMDP-depression scale after one week of amineptine (D7), while 2 patients relapsed after one month of treatment (D28) and were considered to be non-responders. 4. The maximal density of beta-adrenoceptors (Bmax) was significantly decreased at D7 (by 33%) compared to pretreatment level (D0) in the treatment responders and remained lower at D28, although the difference was no longer significant. No alteration in beta-receptor affinity (Kd) was detected during the treatment. 5. These results indicate that treatment with amineptine, an antidepressant drug known to selectively inhibit the dopamine uptake system, can rapidly affect MNL beta-adrenoceptors. 6. Moreover, the present findings show that the reduction in MNL beta-adrenoceptor density, which is associated with a stable clinical improvement, may provide a predictive index for successful antidepressant treatment.

[Different aspects of the cognitive activities of patients with schizophrenia. IV. Imbalance between assertions and negations]. / Quelques aspects des activités cognitives du schizophrène, IV. Déséquilibre des affirmations et des négations.

Not being able to equilibrate affirmations and negations, the schizophrenic patient accedes only exceptionally to the majoring equilibrations of the second and third levels. In the logico-mathematic field, he does not approach the constructive synthetizing generalisations of reasoning. Lacking reflective abstraction, he cannot balance his logico-mathematic reasoning and differentiate what is structurally possible from what is materially possible, thus explaining his inaccessibility to perceive logic necessities, contrasting with the certainties of his delirium. In the logico-experimental domain, he reaches only rarely clause reasoning generalisation, and relapses regularly to the level of inappropriate generalisations of the extended inductive type. It is useless to try to find the "primum movens" of his difficulties, either in his imbalance assimilation/accommodation, or in his impossibility to see his contradictions, or even in his incapacity to equilibrate affirmations and negations. The majoring equilibrations, of which he is unable, are the functional expression of structures which do not follow the linear causality of Laplace's determinism but the circular causality characteristic of teleonomic processes. After a month of neuroleptic treatment, the decompensated schizophrenic's balance between assimilation and accommodation is partially restored.