Configural memory of a blending aromatic mixture reflected in activation of the left orbital part of the inferior frontal gyrus.

Blending aromatic mixtures components naturally fuse to form a unique odor - a configuration- qualitatively different from each component's odor. Repeated exposure to the components either in the mixture or separately, favors respectively, configural and elemental processings. The neural bases of such processes are still unknown. We examined the brain correlates of the experienced-induced configural processing of a well-known model of binary blending odor mixture, the aromatic pineapple blending (AB, ethyl maltol + ethyl isobutyrate). Before fMRI recording, half of the participants were repeatedly exposed to the mixture (AB, group Gmix), with the other half exposed to its separate components (A and B; Gcomp). During the fMRI recording, all participants were stimulated with the mixture (AB) and the components (A and B). Finally, participants rated the number of odors perceived for each stimulus. Gmix perceived the AB mixture as less complex than did Gcomp. While Gcomp perceived the mixture as more complex than its components, Gmix did not. These results show the presence of experience-induced configural or elemental processing of the AB mixture in each group. Contrasting the brain activity of Gcomp and Gmix, when stimulated with AB, revealed higher activation in the left orbital part of the inferior frontal gyrus. This result sheds light on this area's function, commonly found activated in olfactory studies, and closely connected with the lateral orbitofrontal cortex. We discuss the role of this area as a mediator of configural percepts between temporal and orbitofrontal areas involved in configural memory processes.

Habituation and adaptation to odors in humans.

Habituation, or decreased behavioral response, to odors is created by repeated exposure and several detailed characteristics, whereas adaptation relates to the neural processes that constitute this decrease in a behavioral response. As with all senses, the olfactory system continually encounters an enormous variety of odorants which is why mechanisms must exist to segment them and respond to changes. Although most olfactory habitation studies have focused on animal models, this non-systematic review provides an overview of olfactory habituation and adaptation in humans, and techniques that have been used to measure them. Thus far, psychophysics in combination with modern techniques of neural measurement indicate that habituation to odors, or decrease of intensity, is relatively fast with adaptation occurring more quickly at higher cerebral processes than peripheral adaptation. Similarly, it has been demonstrated that many of the characteristics of habitation apply to human olfaction; yet, evidence for some characteristics such as potentiation of habituation or habituation of dishabituation need more support. Additionally, standard experimental designs should be used to minimize variance across studies, and more research is needed to define peripheral-cerebral feedback loops involved in decreased responsiveness to environmental stimuli.

Changes of olfactory abilities in relation to age: odor identification in more than 1400 people aged 4 to 80 years.

The currently presented large dataset (n = 1,422) consists of results that have been assembled over the last 8 years at science fairs using the 16-item odor identification part of the "Sniffin' Sticks". In this context, the focus was on olfactory function in children; in addition before testing, we asked participants to rate their olfactory abilities and the patency of the nasal airways. We reinvestigated some simple questions, e.g., differences in olfactory odor identification abilities in relation to age, sex, self-ratings of olfactory function and nasal patency. Three major results evolved: first, consistent with previously published reports, we found that identification scores of the youngest and the oldest participants were lower than the scores obtained by people aged 20-60. Second, we observed an age-related increase in the olfactory abilities of children. Moreover, the self-assessed olfactory abilities were related to actual performance in the smell test, but only in adults, and self-assessed nasal patency was not related to the "Sniffin' Sticks" identification score.

Dentin structure in familial hypophosphatemic rickets: benefits of vitamin D and phosphate treatment.

OBJECTIVE: To evaluate the outcome of 1-(OH) vitamin D and oral phosphate treatment on dentin structure in patients with familial hypophosphatemic rickets, and expression of SIBLINGs (a family of non-collagenous proteins involved in dentinogenesis) and osteocalcin. PATIENTS AND METHODS: Seven patients with familial hypophosphatemic rickets (age 3-16 years) were studied before or during treatment. Deciduous and permanent teeth were prepared for scanning electron microscopy (SEM) analysis and immunohistochemistry. RESULTS: Untreated or inadequately treated patients had necrotic teeth with impaired dentin mineralization including unmerged calcospherites and accumulation of non-collagenous proteins in wide interglobular spaces. Most of the primary incisors analyzed displayed fissures linking enamel subsurface to pulp horn. These elements may explain the bacterial penetration and dental abscesses despite the absence of carious lesions. Well-treated patients had healthy teeth with good dentin mineralization and little evidence of calcospherites. CONCLUSION: Treatment of hypophosphatemic children with 1-(OH) vitamin D and oral phosphate insures good dentin development and mineralization, and prevents clinical anomalies such as the dental necrosis classically associated with the disease. Starting treatment during early childhood and good adherence to the therapy are mandatory to observe these beneficial effects.

A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxylterminal cytoplasmic tail that causes autosomal dominant hypocalcemia.

Autosomal dominant hypocalcemia (ADH) can result from heterozygous missense activating mutations of the calcium-sensing receptor (CaSR) gene, a G-protein-coupled receptor playing key roles in mineral ion metabolism. We now describe an ADH kindred of three generations caused by a novel CaSR mutation, a large in-frame deletion of 181 amino acids within its carboxylterminal-tail from S895 to V1075. Interestingly, the affected grandfather is homozygous for the deletion but no more severely affected than heterozygous affected individuals. Functional properties of mutant and wild-type (WT) CaSRs were studied in transiently transfected, fura-2-loaded human embryonic kidney (HEK293) cells. The mutant receptor exhibited a gain-of-function, but there was no difference between cells transfected with mutant complementary DNA alone or cotransfected with mutant and WT complementary DNAs, consistent with the similar phenotypes of heterozygous and homozygous family members. Therefore, this activating deletion may exert a dominant positive effect on the WT CaSR. The mutant receptor's cell surface expression was greater than that of the WT CaSR, potentially contributing to its gain-of-function. This novel mutation in the CaSR gene provides the first known examples of a large naturally occurring deletion within a G-protein-coupled receptor's carboxylterminal-tail and of a homozygous, affected individual with ADH.

Home care users' experiences of fiscal constraints. Challenges and opportunities for case management.

With mounting fiscal constraints in home care, case managers find themselves increasingly confined in rationing roles and pressed into a narrow focus on the individual case. These pressures frustrate case management's potential to inform and contribute to more broadly-based improvements in service systems, policy formulation, and resource development. A study of home care users' perspectives in a jurisdiction where fiscal pressures have been rapidly increased reveals how rationing and service reduction affect service recipients and shape their relationships with case managers. The study sheds light on the challenges and opportunities for case managers of practicing in such straitened circumstances. Combined with their own detailed understanding of front-line service delivery, case managers can build on the knowledge of service users' perspectives to make critical contributions to both the well-being of the generally jeopardized populations who need home care and to the broadening of case management practice in keeping with its commitments to advocacy and systems level change.

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.

Levels of neurohypophyseal peptides in the rat during the first month of life. I. Basal levels in plasma, pituitary, and hypothalamus.

Vasopressin, oxytocin, and neurophysin were measured by RIA in the pituitary, hypothalamus, and plasma (except oxytocin) of the rat during the first month of life. In plasma, vasopressin was less than 1.7 microU/ml in most animals. Neurophysin was elevated above adult levles on day 2 and decreased with age. The three peptides were present in the pituitary at birth, but in amounts less than 1% of the adult level. The vasopressin content of the pituitary increased rapidly in the first days after birth, while the levels of oxytocin and neurophysin remained low until 8 days and then increased between 8-21 days. The ratio of vasopressin to oxytocin in the pituitary was 4.4 at birth and reached unity (the ratio in the adult) at 30 days. At birth, the moles of neurophysin in the pituitary relative to the moles of hormone (oxytocin plus vasopressin) was low (0.15), largely due to a molar excess of vasopressin. The ratio of neurophysin to hormone reached unity at 21-30 days. Assays to detect vasotocin gave negative results. It is postulated that a precursor neurophysin which was related to vasopressin was present in the fetal rat but was not measured in our study.

Neurohypophyseal peptides in the developing rat fetus.

The quantitative changes in the content of the neurohypophyseal peptides, neurophysins, oxytocin, and vasopressin, were determined in the developing rat fetus. No neurohypophyseal peptides were found in 12-day fetuses. Neurophysins were first detected at day 13 and increased dramatically on day 14. The hormones vasopressin and oxytocin were not detected at day 13 and were measured at low levels at day 14. A 350-fold molar excess of neurophysin to hormones existed at day 14. From day 14 to day 19 the total content of neurophysin decreased while the content of vasopressin and oxytocin slowly increased. At day 19 there was a near molar equivalency between the content of neurophysin and that of the neurohypophyseal hormones. From day 18 to day 22 there was a sharp increase in the content of vasopressin while the content of neurophysin and oxytocin increased less dramatically. At term there was a molar excess of vasopressin, and the molar ratio of neurophysin to hormone at the time of delivery was 0.12. Measurement of vasopressin by different radioimmunoassays and by bioassay indicated no contribution of arginine-vasotocin to the measured vasopressin.

[Growth retardation after irradiation of a chordoma of the clivus]. / Retard de croissance aprés irradiation d'un chordome du clivus

In a seven year old boy a chordoma of the clivus has been treated by X-ray therapy after partial neurochirurgical resection. A recurrence of the tumor is noted 10 years after at the the border of the X-ray field. The final size of the sexually mature boy is -- 4 DS below the mean with a complete defect in GH secretion after arginin and insulin stimulation. TSH secretion insuficiency and high HPr levels are shown by TRH stimulation test. The length of survey in this particular case has allowed the demonstration of severe stunting growth which is in part a consequence of hypothalamo-pituitary axis irradiation.