Palmoplantar keratoderma caused by a missense variant in CTSB encoding cathepsin B.

BACKGROUND: Palmoplantar keratoderma (PPK) refers to a large group of disorders characterized by extensive genetic and phenotypic heterogeneity. PPK diagnosis therefore increasingly relies upon genetic analysis. AIM: To delineate the genetic defect underlying a case of diffuse erythematous PPK associated with peeling of the skin. METHODS: Whole exome and direct sequencing, real-time quantitative PCR, protein modelling and a cathepsin B enzymatic assay were used. RESULTS: The patient studied had severe diffuse erythematous PPK transgrediens. Pedigree analysis suggested an autosomal dominant mode of inheritance. Whole exome sequencing revealed a heterozygous missense mutation in the CTSB gene, encoding the cysteine protease cathepsin B. Genomic duplications in a noncoding region, which regulates the expression of CTSB, were recently found to cause erythrokeratolysis hiemalis, a rare autosomal dominant disorder of cornification. This mutation affects a highly conserved residue, and is predicted to be pathogenic. Protein modelling indicated that the mutation is likely to lead to increased endopeptidase cathepsin B activity. Accordingly, the CTSB variant was found to result in increased cathepsin B proteolytic activity. CONCLUSION: In summary, we report the identification of the first gain-of-function missense mutation in CTSB, which was found to be associated in one individual with a dominant form of diffuse PPK.

The impact of pollutants from a major northern highway on an adjacent hardwood forest.

Emissions of pollutants from highways can exert multiple stresses on adjacent ecosystems. In this study air concentrations of NO2 and throughfall deposition of inorganic N (NO3- and NH4+), SO42-, Cl-, base cations and several metals were measured in all four seasons along a 1.5km hardwood forest gradient extending away from a major highway (Highway 401) in southern Ontario, Canada. Soil and lichen chemistry and herbaceous plant and epiphytic lichen species composition were measured within the hardwood forest to evaluate impacts of these pollutants. Air concentrations of NO2 and deposition of inorganic N, Cl-, base cations and Cu and Zn in throughfall were significantly elevated within 100m of the road compared with the more distant sites. Concentrations of several pollutants including N (and δ15N), Na+, Al and Fe in epiphytic lichen tissue decreased with distance from the highway, and epiphytic lichen richness was lower at sites within 100m of the road. Despite high throughfall inputs of >15kgNha-1y-1 and 100kgNa+ha-1y-1 within 33m of the highway, for example, there was no significant difference in soil chemistry amongst sites. Plant community composition at sites within 80m of the highway differed from sites located further from the road, but it is unclear whether differences were due to highway emissions or were a result of natural forest edge effects.

Validating the Mental Health Assessment Protocols (MHAPs) in the Resident Assessment Instrument Mental Health (RAI-MH).

For persons with mental illness and addictions, comprehensive assessment of their strengths, preferences and needs is central to person-centred care planning. In this study, the validity of the Mental Health Assessment Protocols (MHAPs) embedded in the Resident Assessment Instrument Mental Health instrument (the mandated assessment system for Ontario adult inpatient psychiatry) is examined, and triggering rates are compared in inpatient and community-based mental health settings. The sample is based on adults admitted to a psychiatric facility (n = 963) and to community mental health programmes (n = 1505) participating in the study. An international panel of mental health experts further evaluated study results. Among the 27 MHAPs, all but one had sensitivity rates above 80%, and the specificity was over 80% for 74% of the MHAPs. The expert panel found that the MHAPs worked well and could be used to support mental health care. The present study found that the MHAPs are valid measures, though more complex triggering algorithms capable of differentiating individuals based on outcomes were suggested to enhance their clinical relevance to care planning. Further, the use of compatible instrumentation in community-based mental health settings was promoted to enhance continuity of care.

Lowered plasma vitamin C, but not vitamin E, concentrations in dementia patients.

BACKGROUND: Alzheimer s disease (AD), according to the free radical hypothesis, affects brain regions where free radical damage occurs. Antioxidant nutrients may help to protect these brain regions. OBJECTIVE: To investigate whether plasma vitamin C and E status is lowered in subjects with AD and dementia. DESIGN: A case control study was conducted in 93 institutionalized subjects aged 65 + yrs. The dementia group (N = 43) included 15 subjects with Alzheimer s Disease (AD) and 28 subjects with senile dementia, while the control group included 50 subjects with no cognitive impairment. Subjects with uncontrolled hypertension and/or diabetes were excluded from the study. Plasma vitamin C and E was determined using the 2,6- dichlorophenolindophenol and the HPLC methods, respectively. Dietary intake, including dietary supplements, was assessed using a 2-day plate-waste method. Cognitive function was measured using the MMSE and nutritional status assessed using the Mini Nutritional Assessment (MNA) tool. RESULTS: The control group had significantly higher scores for the MNA, MMSE and Activities of Daily Living, compared with the dementia group. Controls had a significantly higher plasma vitamin C concentration than dementia patients (median = 0.84 (IQR = 0.54) mg/dl and 0.56 (0.80) mg/dl, respectively; P<0.05). The dementia group were more likely to have sub-optimal plasma vitamin C levels (< 0.6 mg/dl) than control subjects (OR = 2.99; 95 % CI = 0.95 9.79; P<0.05), despite having similar dietary vitamin C intakes. Plasma vitamin C was positively associated with MMSE score (r = 0.21; P<0.05). No difference was found between the groups for either plasma or dietary vitamin E. CONCLUSION: Plasma vitamin C levels were lower in subjects with dementia compared to controls, which was not explained by their dietary vitamin C intakes. This data supports the free radical theory of oxidative neuronal damage. Further investigations of whether supplementation with this vitamin may prevent or delay the progression of cognitive decline in patients with AD and senile dementia appear warranted.

The RAI-PC: an assessment instrument for palliative care in all settings.

Large numbers of persons in most types of healthcare settings have palliative care needs that have considerable impact on their quality of life. Therefore, InterRAI, a multinational consortium of researchers, clinicians, and regulators that uses assessment systems to improve the care of elderly and disabled persons, designed a standardized assessment tool, the Resident Assessment Instrument for Palliative Care (RAI-PC). The RAI-PC can be used for both the design of individual care plans and for case mix and outcomes research. Some elements of this instrument are taken from the resident assessment instrument (RAI) mandated for use in all nursing homes in the United States and widely used throughout the world. The RAI-PC can be used alone or in counjunction with the other assessment tools designed by the InterRAI collaboration: the RAI for homecare (RAI-HC), for acute care (RAI-AC), and for mental health care (RAI-MH). The objective of this study was to field test and carry out reliability studies on the RAI-PC. After appropriate approvals were obtained, the RAI-PC instrument was field tested on 151 persons in three countries in more than five types of settings. Data obtained from 144 of these individuals were analyzed for reliability. The reliability of the instrument was very good, with about 50 percent of the questions having kappa values of 0.8 or higher, and the average kappa value for each of the eight domains ranging from 0.76 to 0.95. The 54 men and 95 women had a mean age of 79 years. Thirty-four percent of individuals suffered pain daily. Eighty percent tired easily; 52 percent were breathless on exertion; and 19 to 53 percent had one or more other symptoms, including change in sleep pattern, dry mouth, nausea and vomiting, anorexia, breathlessness at rest, constipation, and diarrhea. The number of symptoms an individual reported increased as the estimated time until death declined. The "clinician friendly" RAI-PC can be used in multiple sites of care to facilitate both care planning and case mix and outcomes research.

Ultrastructural contributions to an understanding of the cellular mechanisms involved in lizard skin shedding with comments on the function and evolution of a unique Lepidosaurian phenomenon.

Previous reports on the fine structure of lizard epidermis are confirmed and extended by SEM and TEM observations of cell differentiation and the form of shed material from the American anole Anolis carolinensis. Attention is drawn to two issues: 1) the tips of the spinules arising from the mature oberhautchen are markedly curved; this morphology can be seen during differentiation; 2) the median keels of scales from all parts of the body show "naked" oberhautchen cells that lack characteristic spinules, but have a membrane morphology comprising a complex system of serpentine microridges. Maderson's ([1966] J. Morphol. 119:39-50) "zip-fastener" model for the role of the shedding complex formed by the clear layer and oberhautchen is reviewed and extended in the light of recent SEM data. Apparently periodic lepidosaurian sloughing permits somatic growth; understanding how the phenomenon is brought about requires integration of data from the organismic to the molecular level. The diverse forms of integumentary microornamentation (MO) reported in the literature can be understood by considering how the cellular events occurring during the renewal phase prior to shedding relate to the emergence of the form-function complex of the ß-layer, which provides physical protection. Issues concerning the evolutionary origin of lepidosaurian skin-shedding are discussed. J. Morphol. 236:1-24, 1998. © 1998 Wiley-Liss, Inc.

The effect of clozapine on saliva flow rate: a pilot study.

This study examined the effect of clozapine on saliva flow rate. Unstimulated whole saliva was collected from 9 patients taking clozapine (dose range = 50-400 mg/day) and from 8 controls who had never used clozapine. There was no significant difference between the average saliva flow rates in the two groups (p > .10), nor was there significant correlation between saliva flow rate and daily clozapine dose (p > .10). Alternative explanations for observations or complaints of excessive salivation, drooling, or a choking feeling while taking clozapine are proposed.

Ultrastructure of lingual salivary glands in the American chameleon: Anolis carolinensis.

That portion of the dorsal surface of the tongue of Anolis carolinensis that is covered by plumose papillae is underlaid by a series of tubular salivary glands that open between the papillae; glands persist into the posterior zone of the tongue, where they open between cylindriform papillae. Anterior glands are serous in nature--they consist of simple columnar epithelial cells that contain abundant secretory granules exhibiting a variety of substructural patterns. The Golgi apparatus is large and of unusual appearance, with numerous closely packed terminal dilatations and condensing vacuoles. Near the posterior border of the lingual zone covered by plumose papillae, mucous cells begin to appear in the glandular epithelium. More posteriorly, the apical portions of the glands consist entirely of mucous cells, whereas the blind ends of the glands are composed of serous cells. The most posterior glands are of the pure mucous variety. The glands finally disappear a short distance posterior to the cylindriform papillae. The functions of the abundant and highly differentiated salivary glands of the Anolis tongue remain obscure.

Chondrogenic stimulation of embryonic chick limb mesenchymal cells by factors in bovine and human dentine extracts.

Extracts of bovine or human dentine when incorporated into the medium bathing embryonic chick-limb mesenchymal cells caused the stimulation of chondrogenesis. Such extracts were prepared from demineralized bovine or human dentine by suspension in a 4 M guanidinium hydrochloride (GuHCl) solution. After stepwise dialysis down to distilled water to remove the GuHCl, the protein extracts were separated chromatographically on DEAE resin. The crude and separated extracts from both dentines produced morphological changes in the cultured mesenchymal cells similar to those reported for bovine and human adult bone extracts, as well as metachromatic staining with toluidine blue indicating that they stimulated chondrogenesis. Measurements of [35S]-SO4 incorporation and DNA content in the cultures also indicated that the extracts stimulated chondrogenesis but not cell proliferation. The similarity between silver-stained patterns on sodium dodecyl sulphate polyacrylamide gel electrophoresis of corresponding fractions of the bovine and human dentine suggests that they may contain similar or identical proteins.

Papillary morphology of the tongue of the American chameleon: Anolis carolinensis.

Based on regional differences in surface morphology, the dorsum of the tongue of Anolis carolinensis can be subdivided into four distinct zones. The first quarter of the tongue is relatively smooth, whereas the second and fourth quarters are festooned with closely packed cylindriform papillae, which are covered by typical parakeratotic stratified squamous epithelium. The third quarter of the tongue is covered by papillae of novel morphology that we have named "plumose papillae." These are composed of a slender connective tissue core covered by stratified squamous epithelium from whose surface numerous elongated cells radiate. These "plume cells" are about 30-40 microns long and have an extremely irregular nucleus in their expanded terminus. Their stalks are affixed by desmosomes to the deeper cells of the epithelium, and their free surfaces are covered by intricately patterned microplications. Their cytosol contains a dense web of 100-A cytofilaments that may be involved in maintaining the peculiar morphology of the cells. Regardless of type, all lingual papillae of A. carolinensis contain a single longitudinally oriented skeletal muscle fiber that originates from the underlying lingual muscles, raising the possibility that the papillae can be moved at will. The plumose papillae and their retinue of plume cells are unique morphological structures that may be important in mastication and deglutition of food.