New perspectives on the biology and treatment of X-linked hypophosphatemic rickets

This article updates the practicing pediatrician's knowledge of the hypophophatemic disorders that may occur in children. The classic X-linked disorder is emphasized. Details of clinical manifestations, the wide spectrum of disease severity, and complications of the disorder in adults are reviewed. Recent research, new genetic findings, and speculations regarding pathophysiology are discussed. A strategy for approaching medical treatment of X-linked hypophosphatemic rickets is provided, together with complications of treatment and treatment after cessation of growth.     

Housing conditions alter GABAA receptor of alcohol-preferring and -nonpreferring rats

The effects of housing conditions on some functional properties of the GABAA benzodiazepine (BZD) receptor in the cerebral cortex were examined in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats. Compared to rats housed in pairs (P with P and NP with NP), P and NP rats housed individually had 44% (p < 0.005) and 32% (p < 0.01) lower values, respectively, for GABA-stimulated 36Cl- influx into cortical microsacs. The maximal effect (Vmax) of flunitrazepam (FNZ) to enhance GABA-stimulated 36Cl- uptake was 44% higher in individually housed P rats than pair-housed P rats (p < 0.05) and 51% higher than individually housed NP rats (p < 0.05). There was no difference between single and pair-housed NP rats for Vmax values of FNZ enhancement of GABA-stimulated 36Cl- influx. The results show housing conditions can alter some of the functional properties of the GABAA/BZD receptor in the P and NP lines of rats. The differential effect of housing conditions on FNZ enhancement of 36Cl- influx, observed between the lines, may be a result of higher levels of anxiety being produced by brief isolation in the P rat.     

Improved in situ spring constant calibration for colloidal probe atomic force microscopy

In colloidal probe atomic force microscopy (AFM) surface forces cannot be measured without an accurate determination of the cantilever spring constant. The effective spring constant k depends upon the cantilever geometry and therefore should be measured in situ; additionally, k may be coupled to other measurement parameters. For example, colloidal probe AFM is frequently used to measure the slip length b at solid/liquid boundaries by comparing the measured hydrodynamic force with Vinogradova slip theory (V-theory). However, in this measurement k and b are coupled, hence, b cannot be accurately determined without knowing k to high precision. In this paper, a new in situ spring constant calibration method based upon the residuals, namely, the difference between experimental force-distance data and V-theory is presented and contrasted with two other popular spring constant determination methods. In this residuals calibration method, V-theory is fitted to the experimental force-distance data for a range of systematically varied spring constants where the only adjustable parameter in V-theory is the slip length b. The optimal spring constant k is that value where the residuals are symmetrically displaced about zero for all colloidal probe separations. This residual spring constant calibration method is demonstrated by studying three different liquids (n-decanol, n-hexadecane, and n-octane) and two different silane coated colloidal probe-silicon wafer systems (n-hexadecyltrichlorosilane and n-dodecyltrichlorosilane).     

Determination of salsolinol and related catecholamines through on-line preconcentration and liquid chromatography/atmospheric pressure photoionization mass spectrometry

A new analytical approach has been developed for simultaneous measurements of endogenous salsolinol and major catecholamines in brain tissue of experimental animals. This procedure involves a combination of on-line phenyl boronate affinity preconcentration and microcolumn liquid chromatography, followed by mass spectrometry equipped with an atmospheric pressure photoionization (APPI) source. Flow conditions of the APPI source were optimized for detection sensitivity while different dopants were evaluated. The on-line preconcentration was found essential for the sensitivity requirements of salsolinol measurements in the brain tissue from alcohol-preferring rats subjected to different levels of alcohol exposure.     

Biochemical and Structural Characterization of XoxG and XoxJ and Their Roles in Lanthanide-Dependent Methanol Dehydrogenase Activity

Lanthanide (Ln)-dependent methanol dehydrogenases (MDHs) have recently been shown to be widespread in methylotrophic bacteria. Along with the core MDH protein, XoxF, these systems contain two other proteins, XoxG (a c-type cytochrome) and XoxJ (a periplasmic binding protein of unknown function), about which little is known. In this work, we have biochemically and structurally characterized these proteins from the methyltroph Methylobacterium extorquens AM1. In contrast to results obtained in an artificial assay system, assays of XoxFs metallated with La^III, Ce^III, and Nd^III using their physiological electron acceptor, XoxG, display Ln-independent activities, but the K_m for XoxG markedly increases from La to Nd. This result suggests that XoxG′s redox properties are tuned specifically for lighter Lns in XoxF, an interpretation supported by the unusually low reduction potential of XoxG (+172 mV). The X-ray crystal structure of XoxG provides a structural basis for this reduction potential and insight into the XoxG–XoxF interaction. Finally, the X-ray crystal structure of XoxJ reveals a large hydrophobic cleft and suggests a role in the activation of XoxF. These studies enrich our understanding of the underlying chemical principles that enable the activity of XoxF with multiple lanthanides in vitro and in vivo.     

Electron diffraction from nanovolumes of amorphous material using coherent convergent illumination

Using a conventional transmission electron microscope that incorporates a field emission gun it is possible to focus an electron beam to form a small probe (<1nm full-width at half-maximum). Such a probe can then be used to perform high spatial resolution diffraction experiments. The high spatial resolution allows technologically interesting amorphous volumes, such as those found in glassy intergranular phases or in semiconductor implantations, to be investigated directly. In order to achieve the probe characteristics necessary to investigate nanovolumes of material the probe must be highly convergent which results in it being highly coherent. In this paper we examine the effect of coherent convergent illumination on electron diffraction data taken from nanovolumes of amorphous material. It is shown that, for amorphous volumes as small as 1.2nm in diameter, the additional interference effects induced in the diffraction data by the use of coherent convergent illumination are largely suppressed by the lack of order in amorphous materials. This allows the use of deconvolution techniques, developed for the correction of broadening of the diffraction pattern in the case of incoherent illumination, and the subsequent application of reduced density function (G(r)) analysis, to also be used for coherent illumination.     

Localization of the cellular expression of inhibin in trophoblastic tissue

We report four new cases of chordoma of "the mobile spine", all at the L2 level. Diagnosis was often delayed due to predominantly nonspecific low back symptoms; however, neurological involvement is more frequent than in chordoma with a sacrococcygeal localization. No pathognomonic images have been described for any imaging modality, and differential diagnosis should include metastases, chondrosarcoma, and giant-cell tumor. Histopathological analysis can be performed on CT-guided puncture biopsy samples, but a high level of suspicion must be present and, if there is any doubt, immunohistochemical studies should be carried out. Despite being the treatment of choice, complete tumor resection by a double-approach spondylectomy is barely feasible at the L2 level.     

Group II innate lymphoid cells and microvascular dysfunction from pulmonary titanium dioxide nanoparticle exposure

Background

The cardiovascular effects of pulmonary exposure to engineered nanomaterials (ENM) are poorly understood, and the reproductive consequences are even less understood. Inflammation remains the most frequently explored mechanism of ENM toxicity. However, the key mediators and steps between lung exposure and uterine health remain to be fully defined. The purpose of this study was to determine the uterine inflammatory and vascular effects of pulmonary exposure to titanium dioxide nanoparticles (nano-TiO₂). We hypothesized that pulmonary nano-TiO₂ exposure initiates a Th2 inflammatory response mediated by Group II innate lymphoid cells (ILC2), which may be associated with an impairment in uterine microvascular reactivity.

Methods

Female, virgin, Sprague-Dawley rats (8–12 weeks) were exposed to 100 μg of nano-TiO₂ via intratracheal instillation 24 h prior to microvascular assessments. Serial blood samples were obtained at 0, 1, 2 and 4 h post-exposure for multiplex cytokine analysis. ILC2 numbers in the lungs were determined. ILC2s were isolated and phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) levels were measured. Pressure myography was used to assess vascular reactivity of isolated radial arterioles.

Results

Pulmonary nano-TiO₂ exposure was associated with an increase in IL-1ß, 4, 5 and 13 and TNF- α 4 h post-exposure, indicative of an innate Th2 inflammatory response. ILC2 numbers were significantly increased in lungs from exposed animals (1.66?±?0.19%) compared to controls (0.19?±?0.22%). Phosphorylation of the transactivation domain (Ser-468) of NF-κB in isolated ILC2 and IL-33 in lung epithelial cells were significantly increased (126.8?±?4.3% and 137?±?11% of controls respectively) by nano-TiO₂ exposure. Lastly, radial endothelium-dependent arteriolar reactivity was significantly impaired (27?±?12%), while endothelium-independent dilation (7?±?14%) and α-adrenergic sensitivity (8?±?2%) were not altered compared to control levels. Treatment with an anti- IL-33 antibody (1 mg/kg) 30 min prior to nano-TiO₂ exposure resulted in a significant improvement in endothelium-dependent dilation and a decreased level of IL-33 in both plasma and bronchoalveolar lavage fluid.

Conclusions

These results provide evidence that the uterine microvascular dysfunction that follows pulmonary ENM exposure may be initiated via activation of lung-resident ILC2 and subsequent systemic Th2-dependent inflammation.

     

Interpersonal styles of chronically depressed outpatients: Profiles and therapeutic change.

Theoretical accounts posit that chronically depressed individuals are perceived as hostile and/or submissive, which compromises their ability to satisfy their interpersonal needs. The current study assessed the interpersonal tenets of McCullough's (2000) chronic depression theory and examined change in interpersonal functioning following McCullough's treatment for chronic depression (viz., Cognitive-Behavioral Analysis System of Psychotherapy; CBASP). Data derive from a randomized 12-week clinical trial that compared the efficacy of CBASP, nefazodone, and their combination for chronic depression. To assess patients' interpersonal impacts, CBASP therapists completed the Impact Message Inventory (IMI) following an early and a late session. IMI data were compared to normative and clinical comparison samples to assess depression-related interpersonal profiles and clinically significant change in interpersonal functioning. As predicted, chronically depressed patients were initially perceived as more submissive and hostile than the comparison groups. Patients' interpersonal impacts on their therapists changed in adaptive, theoretically predicted ways by the end of CBASP treatment, either with or without medication. Individual-level clinical significance data were less robust. The findings generally substantiate McCullough's interpersonal theory and provide preliminary evidence of change in interpersonal impacts following treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)