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N Kitson

Publications and source records attributed to N Kitson.

13 recordsLinked to original sources

Hypothesis: the epidermal permeability barrier is a porous medium.

The stratum corneum is a complex biological material characterized by very low permeability to water and most other molecules. This material may be thought of as a 'porous medium' composed of impermeable and permeable regions. Intercellular lipid membranes in the stratum corneum are postulated to exist in a mixture of two phases: solid (i.e. impermeable) and liquid crystalline (permeable). The corneocyte envelope is classified as impermeable. Diffusion mechanisms of solutes within, across and between the intercellular lamellae are discussed. This model represents a refinement of previous theories about the physical structures responsible for the low observed permeability of the stratum corneum.

Diffusion↗

What's water got to do with it? A nuclear magnetic resonance study of molecular motion in pig stratum corneum.

The 1H and 2H magnetic resonance signals from pig stratum corneum were measured as a function of hydration. The 1H free induction decay contained two components, one motionally restricted and the other isotropically mobile on the timescale of 10(-5) s. From its T2 decay, the mobile signal was further subdivided into two components; one, which was 11% of the signal and 5.5% of the mass of the dehydrated stratum corneum, was assigned to nonaqueous tissue (likely hydrocarbons) and the other to water. As water content increased from 0 to 0.25 gH2O/gSC, the second moment of the motionally restricted signal decreased from 5.4 x 10(9) to 3.6 x 10(9) s(-2), whereas the water T2 time increased from less than 0.3 ms to 3.3 ms. The 2H quadrupolar echo from stratum corneum hydrated in 2H2O had a signal from motionally restricted deuterons, attributed to deuterons exchanged onto O-H and N-H groups, and a mobile signal from 2H2O. The amount of exchange, 9.5% of the hydrogen sites in the motionally restricted fraction, was close to the number of exchangeable sites on keratin, the most abundant protein in stratum corneum. Our results are consistent with a model in which the bulk of the water interacts closely with the corneocytes in stratum corneum.

Animals↗

A model membrane approach to the epidermal permeability barrier: an X-ray diffraction study.

The permeability of mammalian skin is determined in large part by lamellar lipid domains packed between cells of the upper layer of the epidermis, the stratum comeum. Although these lamellae have features in common with typical biological membranes, they differ in having a lipid population composed mainly of ceramides, cholesterol, and free fatty acids. In our initial studies of the relationship between lipid composition and phase behavior in this unusual system, we used deuterium NMR [Kitson et al. (1994) Biochemistry 33, 6707-6715] to examine aqueous dispersions of nonhydroxylated bovine brain ceramide, cholesterol, and perdeuterated palmitic acid, and found complex phase behavior as a function of temperature and pH, whereas analogous dispersions in which sphingomyelin replaced ceramide resulted in spectra consistent with a fluid lamellar phase under the same conditions. To extend these observations, we examined the same dispersions at pH 5.2 by means of X-ray diffraction. The significant findings are as follows: (1) the ceramide dispersions form complex crystalline phases between room temperature and about 40 degrees C; (2) the majority of the crystalline cholesterol is not in a separate phase; and (3) the analogous sphingomyelin dispersions form a fluid lamellar phase under the same conditions. We conclude that ceramides, even in the presence of considerable mole fractions of cholesterol, can form crystalline lamellar structures. We suggest that the existence of such structures in stratum corneum may be important in the function of the epidermal permeability barrier, and that the interaction between ceramide and cholesterol in other biological membranes may result in regions having unique physical properties.

Animals↗

Neural correlates of thinking in sign language.

Positron emission tomography (PET) was used to identify the brain regions activated during the 'inner signing' of sentences in subjects who were profoundly deaf and normally communicated using sign language. Although this appeared to involve the internal representation of hand and arm movements in space, it activated the left inferior frontal cortex rather than visuo-spatial areas. The activated region corresponds to that engaged during the silent articulation of sentences in hearing subjects. This suggests that 'inner signing' is mediated by similar regions to inner speech, and is consistent with neuropsychological data implicating the left hemisphere in the generation of sign language.

Adult↗

A model membrane approach to the epidermal permeability barrier.

The permeability barrier of mammalian skin is found in unusual intercellular domains in the upper layers of the epidermis, and is composed mainly of three lipid classes: ceramide, cholesterol, and free fatty acid. These are organized as lamellae, but the details of lipid organization are not precisely known. To examine the relationship between lipid composition and phase behavior, aqueous dispersions of bovine brain ceramide, cholesterol, and perdeuterated palmitic acid were examined by 2H NMR and compared to analogous systems in which sphingomyelin replaced ceramide. The sphingomyelin systems give rise as expected to a stable fluid lamellar signal over the temperature range 20-75 degrees C and pH 5.2-7.4, whereas the ceramide dispersions show complex polymorphism as a function of both temperature and pH. Prominent features of the ceramide dispersions containing cholesterol are phase coexistence and the presence of a "solid" phase in which molecular motion is more inhibited than in a classical phospholipid gel phase: T1z measurements indicate that lateral diffusion of the palmitic acid probe effectively does not occur. In the absence of cholesterol, a fluid lamellar signal is not observed, but the appearance of a "solid" signal is also influenced by the pH. In the presence of cholesterol, a fluid lamellar signal is present at 50 degrees C, and the 2H NMR order parameter profile is very similar to that derived from the analogous sphingomyelin dispersions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Models of stratum corneum intercellular membranes: 2H NMR of macroscopically oriented multilayers.

Deuterium NMR was used to characterize model membrane systems approximating the composition of the intercellular lipid lamellae of mammalian stratum corneum (SC). The SC models, equimolar mixtures of ceramide:cholesterol:palmitic acid (CER:CHOL:PA) at pH 5.2, were contrasted with the sphingomyelin:CHOL:PA (SPM:CHOL:PA) system, where the SPM differs from the CER only in the presence of a phosphocholine headgroup. The lipids were prepared both as oriented samples and as multilamellar dispersions, and contained either perdeuterated palmitic acid (PA-d31) or [2,2,3,4,6-2H5]CHOL (CHOL-d5). SPM:CHOL:PA-d31 formed liquid-ordered membranes over a wide range of temperatures, with a maximum order parameter of approximately 0.4 at 50 degrees C for positions C3-C10 (the plateau region). The quadrupolar splitting at C2 was significantly smaller, suggesting an orientational change at this position, possibly because of hydrogen bonding with water and/or other surface components. A comparison of the longitudinal relaxation times obtained at theta = 0 degrees and 90 degrees (where theta is the angle between the normal to the glass plates and the magnetic field) revealed a significant T1Z anisotropy for all positions. In contrast to the behavior observed with the SPM system, lipid mixtures containing CER exhibited a complex polymorphism. Between 20 and 50 degrees C, a significant portion of the entire membrane (as monitored by both PA-d31 and CHOL-d5) was found to exist as a solid phase, with the remainder either a gel or liquid-ordered phase. The proportion of solid decreased as the temperature was increased and disappeared entirely above 50 degrees C. Between 50 and 70 degrees C, the membrane underwent a liquid-ordered to isotropic phase transition. These transitions were reversible but displayed considerable hysteresis, especially the conversion from a fluid phase to solid. The order profiles, relaxation behavior, and angular dependence of these parameters suggest strongly that both the liquid-ordered CER- and SPM-membranes are bilayers. The unusual phase behavior observed for the CER-system, particularly the observation of solid-phase lipid at physiological temperatures, may provide insight into the functioning of the permeability barrier of stratum corneum.

Animals↗

Psychiatric disorder in deaf and hearing impaired children and young people: a prevalence study.

Psychiatric screening questionnaires for deaf children and adolescents were piloted in a group of 62 children, aged 11-16 years, attending a residential school. The questionnaires, Parent's Checklist (PCL) and Teacher's Checklist (TCL) were then used to screen a group of 93 children attending one Deaf School and three Hearing Impaired Units (HIU). Psychiatric assessments were conducted with a highly structured diagnostic interview, the Child Assessment Schedule (CAS). The interview with signing deaf children was conducted with a sign language interpreter. The prevalence of psychiatric disorder in the whole group was 50.3%, 42.4% in the group attending the Deaf School and 60.9% for the group attending the HIUs. An aetiological model of psychiatric disorder in this group is proposed.

Adolescent↗

Models of stratum corneum intercellular membranes: the sphingolipid headgroup is a determinant of phase behavior in mixed lipid dispersions.

During formation of the intercellular membranes of mammalian stratum corneum, sphingomyelin and glucosylceramide are converted enzymatically to ceramide. To model in isolation the possible effect of such a lipid modification on the phase behavior of the ensemble, we used proton and deuterium nuclear magnetic resonance to compare an equimolar dispersion of bovine brain sphingomyelin, cholesterol, and perdeuterated palmitic acid (at pH 6.2), with an equivalent dispersion in which bovine brain ceramide was substituted for sphingomyelin. While the sphingomyelin dispersions remain in a homogeneous fluid lamellar phase from 20-75 degrees C under these conditions, those containing ceramide display complex polymorphism.

Ceramides↗

The influence of cholesterol 3-sulphate on phase behaviour and hydrocarbon order in model membrane systems.

Cholesterol 3-sulphate (CS) is a component of the intercellular lipid found in the uppermost layer of human epidermis (the 'stratum corneum') and is thought to play an important role in tissue cohesion. In this investigation we have compared the influence of cholesterol (CH) and CS on the gel-to-liquid crystalline phase behaviour, the polymorphic phase behaviour, and the hydrocarbon order profile in selected model membranes. It is shown that in sphingomyelin (SPM) systems, the presence of equimolar amounts of either CH or CS eliminates the gel-to-liquid crystalline transition as detected by calorimetry. Similarly, in 1-palmitoyl,2-oleoyl-phosphatidylethanolamine (POPE) dispersions containing a perdeuterated palmitoyl chain (POPE-d31), it is shown that both CH and CS exert an ordering effect as determined by 2H-NMR techniques, however, CS is less potent at temperatures both above and below that of the main transition for the native phospholipid. Alternatively, in mixed systems containing dioleoylphosphatidylethanolamine (DOPE) and SPM (DOPE/SPM, 6:1 mol/mol) CH promotes thermotropic L alpha-->HII phase transitions, whereas CS stabilizes the bilayer organization. These bilayer stabilization effects can be diminished by addition of Ca2+. These effects are consistent with a larger area per molecule of CS as compared to CH, presumably related to the presence of the negatively charged sulphate moiety of CS.

Cell Membrane↗

Prelingual deafness and psychiatry.

This article provides an introduction to the neglected area of psychiatry and prelingual deafness. 'Deafness' refers to prelingual profound deafness except where indicated, although many of the observations apply to some extent to prelingually partially hearing people.

Communication↗

Gap junctions in human sebaceous glands.

An examination of human seabaceous glands by transmission electron microscopy has revealed the presence of gap junctions. The junctions are found in abundance between differentiating cells, and annular forms are also seen. The possible significance of this new finding is briefly discussed.

Cell Differentiation↗