Interactions of myristic acid with bovine serum albumin: a 13C NMR study.

Interactions of myristic acid with bovine serum albumin were studied by 13C NMR spectroscopy at 50.3 MHz using 90% isotopically substituted [1-13C]-, [3-13C]-, and [14-13C]myristic acids, either individually or in a combination of all three with albumin. At pH 7.4, two or more resonances of different intensities were observed for each 13C-enriched myristic acid. Carboxyl and methylene C-3 resonances corresponding to the major myristic acid environment(s) exhibited pH-dependent chemical shift changes indicative of protonation below pH 6.7; in contrast, carboxyl groups in minor environments were resistant to protonation. 13C NMR spectra obtained as a function of the molar ratio of [3-13C]- and [14-13C]myristic acid to bovine serum albumin (from 0.7 to 5.6) revealed at least two narrow resonances for each carbon at all molar ratios. Thus, bovine serum albumin binding sites for myristic acid are heterogeneous with respect to titration behavior and with respect to the local magnetic environment at both the polar and the nonpolar ends of the fatty acid. The narrow resonances observed for the methylene and methyl carbons are inconsistent with complete immobilization of the protein-bound acid molecules. Together with spin- lattice relaxation times and nuclear Overhauser enhancements, the linewidth results indicate that bound myristic acid has internal motions that are rapid compared with overall protein tumbling and that the C-3 methylene carbon is more restricted than the terminal methyl carbon.     

Optimizing conventional therapies for inflammatory bowel disease

Conventional therapies remain the mainstay of treatment for most patients with inflammatory bowel disease (IBD), with only a minority of patients requiring biologic therapies. Recently, attention has focused on optimizing dosing strategies for biologic agents; however, of equal importance are recent advances in the optimization of conventional IBD therapies. Newer aminosalicylate formulations demonstrate similar efficacy with a reduced pill burden and less frequent dosing, while new corticosteroid preparations may retain efficacy with a significantly improved safety profile. The limited indications for antibiotics and probiotics have been further refined by recent data, although uncertainties remain. Advances in the understanding of thiopurine metabolism continue to improve dose optimization and the potential for deliberate therapeutic manipulation with adjunctive therapies. An improved knowledge of intracellular methotrexate metabolism may translate to similar opportunities in the future. This article discusses recent advances relevant to clinical practice today.     

Cerebrovascular and neurological perspectives on adrenoceptor and calcium channel modulating pharmacotherapies

Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects – and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders.     

Facial Perception in Autism

Disturbances in gaze and patterns of facial interaction are prominent aspects of social dysfunction in autism; the nature of this disturbance has up to the present been unclear. This study examined the ability of autistic subjects to use the human face as a source of information. Autistic and age- and MA-matched retarded control subjects assembled a series of puzzles displaying photographs of human faces; puzzles differed in complexity, familiarity of the faces and configuration (normal vs scrambled faces). Significant effects of all three factors, but not of diagnostic group, were observed. The autistic subjects did not exhibit specific deficits in perception of faces.     

Concurrent validity and classification accuracy of the Leiter and Leiter-R in low-functioning children with autism

The concurrent validity of the Leiter International Performance Scale (Leiter) and Leiter International Performance Scale–Revised (Leiter-R) was examined in a sample of children with autism who could not be assessed with more traditional measures of intelligence (e.g., the Wechsler scales). The sample consisted of 26 children ranging in age from 4 to 16 years. The correlation between the Leiter scales was high (r = .87), and there was a difference of 3.7 points between the two mean scores, nonsignificant at both statistical and clinical levels. However, significant intraindividual discrepancies were present in 10 cases, 2 of which were both large (24 and 36 points) and clinically meaningful. The mean profile of performance on Leiter-R subtests is also presented for this sample of children with autism, to allow for comparison with other groups. Based on the results of this initial evaluation, together with the current normative data, good psychometric properties, and availability of global and subtest scores with the Leiter-R, the instrument is generally recommended for use with children with autism. However, because of changes in the design of the Leiter-R, there may be greater clinical success with the original Leiter for those children who are very low functioning and severely affected, particularly younger children.     

Experimental studies of the combined use of vitreous substitutes of high and low specific gravity.

The combined use of high and low specific gravity liquid vitreous substitutes has been studied in the rabbit. Eyes having undergone 1) vitreous replacement with silicone liquid combined with a perfluoropolyether liquid of high viscosity; 2) replacement with the perfluoropolyether or silicone alone; or 3) vitrectomy only (control) were compared under conditions of a cell-injection model of traction retinal detachment. Some of the control eyes (3 out of 9) and silicone-filled eyes (2 out of 10) developed total retinal detachments involving all quadrants; in the silicone-filled eyes the detachments extended behind the silicone globule. Conversely, in the eyes undergoing replacement with the two liquids or with the perfluoropolyether liquid alone, retinal detachments never extended to the inferior quadrants underlying the perfluoropolyether globule. In other experiments, the tendency toward emulsification of a low-viscosity perfluorocarbon liquid was reduced when it was used in combination with silicone liquid, in comparison to when this liquid was used alone.     

Evaluation of the blood-aqueous barrier after vitreous replacement with perfluoropropane gas and liquid silicone.

Fluorophotometric measurements of blood-aqueous barrier permeability after intravitreal injection of perfluoropropane gas in rabbit eyes revealed fluorescein leakage immediately after injection; 3 days later, recovery of barrier integrity had begun to occur and 7 days and 14 days after gas injection, when the gas bubble was still in the eye, anterior chamber fluorescein concentrations were normal. Similarly, in eyes undergoing vitrectomy and injection of silicone liquid or vitrectomy only, anterior chamber fluorescein levels were elevated 3 days and 1 week after surgery. Nevertheless, normal barrier integrity was reestablished in both the silicone-filled eyes and the vitrectomized eyes after 1 week. Since there was no difference between the group injected with silicone and the group that underwent vitrectomy only with respect to anterior chamber fluorescein concentration at any of the times studied, it is concluded that the temporary disruption of the blood-aqueous barrier is associated with the surgical procedure rather than the presence of silicone liquid in the vitreous cavity.     

Sézary syndrome associated with sideroblastic anaemia

A 66-year-old man with acquired sideroblastic anaemia and Sézary syndrome is described. This is believed to be the first such case reported in the literature. We speculate on the possibility that a common stem cell defect could account for the simultaneous development of the two abnormalities. Other features of this case of Sézary syndrome are discussed in relation to previous reports on patients with this disease.     

Control of lead and trail limbs during obstacle crossing following stroke

BACKGROUND AND PURPOSE: Obstacle crossing is compromised following stroke. The purpose of this study was to quantify modifications during obstacle clearance following stroke. SUBJECTS: Twelve subjects with stroke and 12 subjects without stroke participated in the study. METHODS: Kinematic variables were measured while participants crossed a 4-cm-high obstacle. Subjects with stroke walked at a self-selected speed; subjects without stroke walked at a comparable speed and at a self-selected speed. RESULTS: Several modifications were observed following stroke with both groups walking at self-selected speeds. The affected lead limb was positioned closer to the obstacle before crossing. Affected trail-limb clearance over the obstacle was reduced. Both affected and unaffected lead and trail limbs landed closer to the obstacle after clearance. Swing time was increased in the affected lead limb after obstacle clearance. Fewer modifications were detected at matched walking speed; the trail limb still landed closer to the obstacle. DISCUSSION AND CONCLUSION: Modifications during obstacle crossing following stroke may be partly related to walking speed. The findings raise issues of safety because people with stroke demonstrated reduced clearance of a 4-cm obstacle and limb placement closer to the obstacle after clearance.     

Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations

Case-control studies have successfully identified many significant genetic associations for complex diseases, but lack of replication has been a criticism of case-control genetic association studies in general. We selected 12 candidate genes with reported associations to chronic obstructive pulmonary disease (COPD) and genotyped 29 polymorphisms in a family-based study and in a case-control study. In the Boston Early-Onset COPD Study families, significant associations with quantitative and/or qualitative COPD-related phenotypes were found for the tumor necrosis factor (TNF)-alpha -308G>A promoter polymorphism (P < 0.02), a coding variant in surfactant protein B (SFTPB Thr131Ile) (P = 0.03), and the (GT)(31) allele of the heme oxygenase (HMOX1) promoter short tandem repeat (P = 0.02). In the case-control study, the SFTPB Thr131Ile polymorphism was associated with COPD, but only in the presence of a gene-by-environment interaction term (P = 0.01 for both main effect and interaction). The 30-repeat, but not the 31-repeat, allele of HMOX1 was associated (P = 0.04). The TNF -308G>A polymorphism was not significant. In addition, the microsomal epoxide hydrolase "fast" allele (EPHX1 His139Arg) was significantly associated in the case-control study (P = 0.03). Although some evidence for replication was found for SFTPB and HMOX1, none of the previously published COPD genetic associations was convincingly replicated across both study designs.