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Biomedical subjects

L Hammer

Publications and source records attributed to L Hammer.

At least 19 recordsLinked to original sources

[Cardiogenic shock due to acute myocarditis complicating leptospirosis].

A 48 year old man was admitted to the intensive care unit with septicaemic shock associated with febrile jaundice and anuric renal failure. Within hours, he developed cardiogenic shock with multi-organ failure due to an acute myocarditis refractory to catecholamines and requiring intra-aortic balloon pumping. The diagnosis was an ictero-haemorrhagic leptospirosis, the outcome of which was finally favourable. Myocarditis is an underestimated complication of leptospirosis because it is often symptomless. The main signs are arrhythmias, conduction defects and ST-T wave abnormalities which have little clinical expression. The disease may progress and is sometimes fatal. Leptospirosis myocarditis should therefore be carefully considered because of its potential severity and its reversibility with appropriate antibiotic therapy and also the necessity of initial management in a specific infrastructure.

Humans↗

Reversible H-induced switching of the magnetic easy axis in Ni/Cu(001) thin films.

A reversible switching of the easy axis of magnetization for Ni on Cu(001) from in plane to out of plane is found by changing the partial pressure of hydrogen in the gas phase around the sample, allowing even for oscillations of the magnetization direction. A quantitative low-energy electron diffraction study of the diffracted intensity versus electron energy [I(E)] shows that the hydrogen-induced spin reorientation transition is accompanied by changes of the tetragonal distortion of the topmost Ni layer upon hydrogen adsorption. Surprisingly, the orientation switch to perpendicular to the surface comes with a relaxation, i.e., reduction of the film's tetragonal distortion rather than its amplification.

Journal Article↗

First-principles-based surface phase diagram of fully relaxed binary alloy surfaces.

The combination of density-functional theory (DFT) calculations of geometrically fully relaxed binary alloy surfaces with concepts from statistical physics is applied to construct a DFT-based phase diagram for a binary alloy surface. As a first example, we studied the appearance of Co antisite atoms at CoAl(100) surfaces. The structural parameters as multilayer relaxations, surface buckling, lateral order, and segregation profile of the predicted stable surface phases are in excellent agreement with experimental structure determinations applying low-energy electron diffraction.

Journal Article↗

Hydrogen-induced self-organized nanostructuring of the Ir(100) surface.

We show that the Ir(100) surface forms a new nanostructure in a self-organized way when its reconstructed equilibrium surface is exposed to hydrogen. Scanning tunneling microscopy and quantitative low-energy electron diffraction retrieve that a long-range ordered superlattice of defect-free Ir chains with average lateral spacing of 1.36 nm and micrometer lengths develops. This can be used as a template for the formation of other nanostructures as is demonstrated.

Journal Article↗

[Cardiovascular consequences of obstructive sleep apnea syndrome].

PURPOSE: This article is an update of past and current data on the relationship between obstructive sleep apnea syndrome and cardiovascular diseases. CURRENT KNOWLEDGE AND KEY POINTS: Obstructive sleep apnea syndrome is a common, but under-recognised, condition and should not be considered simplistically as the association of snoring and obesity. It may be suspected by the clinical history but a definite diagnosis requires the practice of polysomnography. Numerous studies have found a significant relationship between the presence of obstructive sleep apnea syndrome and the occurrence of cardiovascular events. Nonetheless, a definite causal relationship has only been established for the occurrence of hypertension. There are multiple immediate and delayed cardiovascular responses to the apneic events and thus there are many possible physiopathological mechanisms to explain the association of obstructive sleep apnea and cardiac and vascular events, the primary one being sympathetic hyperactivity. The prognosis of obstructive sleep apnea syndrome is closely related to the incidence of cardiovascular events. FUTURE PROSPECTS AND PROJECS: The existence of an independent relationship between obstructive sleep apnea syndrome and atherosclerosis is not yet demonstrated. The beneficial effects of continuous positive airway pressure, the treatment of choice for this condition, on the incidence of cardiovascular diseases remains to be confirmed although recent studies suggest that correct treatment of obstructive sleep apnea syndrome by continuous positive airway pressure may reduce the cardiovascular risk and in particular that of hypertension.

Arteriosclerosis↗

Segregation in strongly ordering compounds: a key role of constitutional defects.

For the example of the B2 CoAl(100) surface, we demonstrate that even slight deviations from an ordered alloy's ideal stoichiometry in a subsurface region or in the bulk can drastically affect its surface composition. By experimental surface analysis and first-principles calculations, we show that Co antisite atoms segregate to the very surface, driven by the same strong interactions which enforce order in the bulk. Our findings are consistent with the lack of antisite segregation we found earlier for the much weaker ordering FeAl(100), and resolve contradictory reports for NiAl(100).

Journal Article↗

Metastatic phaeochromocytoma: risks of diagnostic needle puncture and treatment by arterial embolisation.

A 62-year-old man had an acute episode of hypertension 72 h after fine needle aspiration biopsy of an intra- hepatic nodule. The patient had been operated 3 years previously for a right adrenal phaeochromocytoma with no evidence of metastases at that time. Thus, a relapse of the tumour was postulated and confirmed by raised levels of urinary metanephrines. The extent of the metastases precluded surgical intervention and thus localised embolisation was proposed and permitted a clinical stabilisation over 8 months. This case indicates the necessity of long-term post-operative follow-up of phaeochromocytoma as well as the dangers of fine needle aspiration biopsy of metastases from this kind of tumour. Treatment of malignant phaeochromocytoma is difficult and embolisation was a useful therapeutic alternative in this case where the metastases were well defined.

Adrenal Gland Neoplasms↗

Predicting children's reported eating disturbances at 8 years of age.

OBJECTIVES: To examine differential parental influences on eating attitudes and behaviors of 8-year-old children with a specific focus on gender effects and to assess the specificity of this relationship. METHOD: One hundred eight infants were monitored from birth and interviewed at age 8 for eating disturbances and negative affect with an adaptation of the McKnight Risk Factor Survey. Parental measures included the Three Factor Eating Questionnaire subscales Disinhibition and Restraint as well as body mass index, assessed at study entry. RESULTS: No gender differences were found for frequencies of children's self-reported eating disturbances. Higher maternal restraint scores predicted worries about being too fat in girls but not in boys. Higher maternal disinhibition scores also differentially predicted weight control behaviors in their daughters. Negative affect in the child was (weakly) predicted by higher maternal body mass index. No association between paternal predictors of disturbed eating and the child's eating disturbances and negative emotionality was found. CONCLUSIONS: The impact of maternal eating disorders and disturbances is much stronger than that of fathers and is specifically directed at their daughters. The clinical importance of these disturbances in terms of precursors of adolescent eating disorders has to be determined by monitoring the sample through puberty.

Adult↗

A prospective study of the influence of eating-disordered mothers on their children.

OBJECTIVE: This study examined the effects of eating disordered mothers on their children. METHOD: Women with a past or present eating disorder (ED; N = 41) and non-eating disordered women (NED); N = 153) and their offspring were followed prospectively. RESULTS: Female infants of ED mothers sucked significantly faster and were weaned 9 months later than offspring of NED mothers. ED mothers fed their children on a less regular schedule, used food for nonnutritive purposes, and demonstrated significantly higher concern about their daughters' weight than NED mothers from 2 years of age onward. At 5 years, the offspring of ED mothers were reported to demonstrate greater negative affect than the offspring of NED mothers. DISCUSSION: The female offspring of ED mothers demonstrate a high avidity for feeding early in life which, combined with increased maternal concern over their daughters weight and the use of food for nonnutritive purposes, may pose a serious risk for the later development of an eating disorder.

Adult↗

Serine 232 and methionine 272 define the ligand binding pocket in retinoic acid receptor subtypes.

The transcriptional response mediated by retinoic acid involves a complex series of events beginning with ligand recognition by a nuclear receptor. To dissect the amino acid contacts important for receptor-specific ligand recognition, a series of retinoic acid receptor (RAR) mutants were constructed. Transcriptional studies revealed that serine 232 (Ser232) in RARalpha and methionine 272 (Met272) in RARgamma are critical residues for the recognition of their respective receptor-selective analogs. The identification of these key amino acids in the ligand binding pocket is confirmed by the reported crystal structure of RARgamma. Interestingly, the serine at position 232 in RARalpha gives an explanation for the observed differences in the affinity of the naturally occurring ligand, all-trans-retinoic acid (t-RA), in this receptor compared with that for the other receptors, since hydrogen bonding would not be permitted between the hydroxyl of serine and the hydrophobic linker of t-RA. Using this model, a molecular mechanism for the transcriptional antagonism of a synthetic analog is suggested that involves an alteration in the structure of the receptor protein in the region around the AF2 domain in helix 12.

HeLa Cells↗

Retinoic acid receptor beta,gamma-selective ligands: synthesis and biological activity of 6-substituted 2-naphthoic acid retinoids.

In search for retinoic acid receptor (RAR) selective ligands, a series of 6-substituted 2-naphthoic acid retinoids were synthesized and evaluated in vitro in a transactivation assay and a competition binding assay for all RARs. These derivatives, in general, showed RAR beta,gamma selectivity. Among these naphthoic acids, oxime derivative 12 was identified as a potent RAR gamma-selective retinoid, while olefinic derivative 11 was found to be comparable to retinoic acid and slightly RAR beta,gamma selective. For the bioassays, a general correlation was observed between the binding affinity of the ligand to the receptors and the potency of the compounds in the transactivation assay. The structure-activity relationship of these naphthoic acids will be discussed.

Binding, Competitive↗

Weight concerns influence the development of eating disorders: a 4-year prospective study.

The authors examined factors prospectively associated with age of onset of partial syndrome eating disorders over a 4-year interval in a community sample (N = 877) of high school-age adolescent girls. Four percent developed a partial syndrome eating disorder over the interval. A measure of weight concerns was significantly associated with onset in a multivariate Cox proportional hazard analysis (p < .001). Girls scoring in the highest quartile on the measure of weight concerns had the highest incidence (10%) of partial syndrome onset, whereas none of the girls in the lowest quartile developed eating disorder symptoms. This finding is consistent with both theoretical and clinical perspectives and may represent a useful step toward the establishment of a rational basis for the choice of a prevention intervention target.

Adolescent↗

The N-terminal portion of domain E of retinoic acid receptors alpha and beta is essential for the recognition of retinoic acid and various analogs.

Utilizing a strategy involving domain exchange between retinoic acid receptors alpha and beta (RAR alpha and RAR beta) and monitoring the transcriptional activity of the resulting chimeric receptors with receptor-selective retinoids, we identified a 70-aa region within the N-terminal portion of the RAR alpha and -beta domain E which is important for an RAR alpha- or RAR beta-specific response. Two amino acid residues within this region, serine-232 (S232) and threonine-239 (T239) in RAR alpha and the corresponding alanine-225 (A225) and isoleucine-232 (I232) in RAR beta, were found to be essential for this effect. In addition, binding studies using the chimeric receptors expressed in Escherichia coli showed that the N-terminal portion of domain E was also important for the characteristic binding profile of t-RA and various retinoids with RAR alpha or RAR beta. Structural predictions of the primary amino acid sequence in this region indicate the presence of an amphipathic helix-turn-helix structure with five hydrophobic amino acids that resemble a leucine zipper motif. The amino acid residues identified by domain swapping, S232 and T239 in RAR alpha and A225 and I232 in RAR beta, were found within the hydrophobic face of an alpha-helix in close proximity to this zipper motif, suggesting that the ligand may interact with the receptor in the region adjacent to a surface involved in protein-protein interactions. This finding may link ligand binding to other processes important for transcriptional activation.

Amino Acid Sequence↗

Retinoic acid receptor gamma mediates topical retinoid efficacy and irritation in animal models.

Among retinoic acid receptors (RARs) alpha, beta, and gamma, the messenger RNA level of RAR-gamma is the most readily detectable by Northern blotting in human and mouse skin. This observation suggests that RAR-gamma may play a critical role in the modulation of the therapeutic benefits and side effects of retinoids in skin. To test this hypothesis, 11 RAR-gamma selective retinoids were synthesized based on three related structures. Each compound was found to prefer RAR-gamma when assessed by retinoid-induced transcriptional activity (RAR-gamma > RAR-beta > RAR-alpha). The apparent Kd for binding to recombinant receptor protein was found to follow a similar trend. To correlate this receptor selectivity with in vivo activity, the compounds were tested topically in the Rhino mouse utriculi reduction and rabbit irritation models, two assays widely used to screen retinoids for efficacy and side effects, respectively. The results indicated that for these compounds, both efficacy in the utriculi reduction assay and irritation potential in rabbits correlated positively with the RAR-gamma transactivation activity, with r2 of 0.9 and 0.8, respectively. These data suggest that RAR-gamma is an important regulator of retinoic acid efficacy in skin and further, that the irritation associated with the use of retinoids is most likely a receptor-mediated process.

Animals↗

Role of retinoic acid receptor gamma in the Rhino mouse and rabbit irritation models of retinoid activity.

The three retinoic acid receptors (RAR alpha, RAR beta and RAR gamma) are known to modulate the transcription of target genes through interaction of the individual receptors with their naturally occurring ligand, retinoic acid (RA). Since RA has multiple effects in vivo, considerable effort has recently been devoted to finding selective compounds to elucidate the functions of individual receptors and to relate these functions to specific in vivo effects. The racemic synthetic retinoid 6-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)hydroxy-methyl]-2- naphthalene carboxylic acid has recently been identified as an RAR gamma-selective agonist. A synthetic method involving lipase-mediated transformation has been developed to prepare the individual enantiomers. Discrimination between the two enantiomers is seen in both transcriptional activity and binding to recombinant receptors with the (S)-enantiomer being the more active. Differences between the two compounds are also seen in the Rhino mouse utriculi reduction assay and the rabbit irritation model. In both animal models, the (S)-enantiomer consistently gave a greater response. Taken together, these results suggest that the activity and irritation seen with RA and related compounds is receptor mediated. Further, the strong selectivity of the compounds reported here for RAR gamma suggests that this receptor plays an important role in these in vivo biological activities. The discrimination between these enantiomers may be useful in the design of novel retinoids with uniquely defined biological properties.

Animals↗