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The article presents an interview with dermatologist Sam Shuster. It includes information on Sam's association with University College London, University of Newcastle, and Royal College of Physicians. It presents Sam's views on dermatology, leadership in academic society, and scope of dermatology and clinical research.

AbstractThe P2X3 receptor subunit, a member of the P2X family of ATP‐gated ion channels, is almost exclusively localized in sensory neurons. In the present study, we sought to gain insight into the role of P2X3 and P2X3‐containing neurons in sensory transmission, using immunohistochemical approaches. In rat dorsal root ganglia (DRG), P2X3‐immunoreactivity (‐ir) was observed in small‐ and medium‐sized neurons. Approximately 40% of DRG neuronal profiles in normal rats contained P2X3‐ir. In rats that had received neonatal capsaicin treatment, the number of P2X3‐positive neurons was decreased by approximately 70%. Analysis of the colocalization of P2X3‐ir with cytochemical markers of DRG neurons indicated that approximately 94% of the P2X3‐positive neuronal profiles were labelled by isolectin B4 from Bandeiraea simplicifolia, while only 3% contained substance P‐ir, and 7% contained somatostatin‐ir. In dorsal horn of rat spinal cord, P2X3‐ir was observed in the inner portion of lamina II and was reduced subsequent to dorsal rhizotomy, as well as subsequent to neonatal capsaicin treatment. Finally, P2X3‐ir accumulated proximal to the site of sciatic nerve ligation, and was seen in nerve fibres in skin and corneal epithelium. In summary, our results suggest that P2X3 is expressed by a functionally heterogeneous population of BSI‐B4‐binding sensory neurons, and is transported into both central and peripheral processes of these neurons. [ABSTRACT FROM AUTHOR]

1. The kinetics of weal formation and disappearance following intradermal injection of histamine, compound 48/80 and antigen were measured in indomethacin and inert geltreated human forearm skin. 2. Rates of formation went in descending order for histamine, 48/80 and antigen; rate constants of disappearance for equal sized weals were the same for histamine and 48/80 but were much less for antigen. The corresponding half-lives were 77, 73 and 160 min for histamine, 48/80 and antigen weal disappearance respectively. 3. Cyclo-oxygenase inhibition by topical indomethacin had no effect either on the immediate weal and flare responses or on the rates of formation and disappearance of the weals. 4. These findings together with previous studies using H1-receptor antagonists indicate that 48/80 acts by histamine release but that antigen releases both histamine and an additional material or materials which are not related to cyclo- oxygenase activity. 5. Exacerbation of chronic idiopathic urticaria by cyclo-oxygenase inhibitors is therefore likely to be part of the urticarial disease process. [ABSTRACT FROM AUTHOR]

1. Nedocromil 2% iontophoresed into human skin had no effect on wealing produced by intradermal histamine, 48/80 or house dust mite antigen. 2. Iontophoresis of 0.002-2% nedocromil itself resulted in dose-related wealing. 3. This wealing was reduced by 62 +/- 8% s.e. mean by the H1- receptor antagonist terfenadine which decreased histamine wealing by 68 +/- 2% s.e. mean. 4. Nedocromil may therefore act as a weak agonist on a skin mast cell receptor concerned with histamine release. [ABSTRACT FROM AUTHOR]

Topical 1% indomethacin had no effect on chronic stable plaque psoriasis in an open controlled study using subjective clinical scores nor in a randomised double-blind inert base controlled study using both subjective and objective measurements of lesional response; nor did it initiate or affect the development of psoriasis after cold injury. Previous studies are reviewed and it is concluded that the evidence does not support the hypothesis which relates psoriasis to eicosanoids produced by lipoxygenase activity. [ABSTRACT FROM AUTHOR]

1 The effect of topical arachidonic acid on anthralin inflammation was studied using sequential measurements of erythema (reflectance photometry) and oedema (calipers). 2 Topical arachidonic acid in concentrations which produced a small short-lived inflammatory response greatly augmented the initial phase and depressed the later phase of the inflammatory response to anthralin. 3 The initial augmentation was inhibited by concomitant administration of alpha-tocopherol. 4 It is suggested that free radical formation by anthralin has a direct action on membrane substrates such as arachidonic acid forming inflammatory products by a non-enzymic process. [ABSTRACT FROM AUTHOR]

Weal and flare histamine dose-responses were measured in 30 normal subjects and 15 patients with chronic idiopathic urticaria. The log dose-response curves were shifted to the left corresponding to an increase in histamine potency of 2.5 for weal and 3.1 for flare. An enhanced response to histamine may be important in chronic idiopathic urticaria and comparison of potency of antihistamines in different subjects may be unreliable where initial weal response is abnormal. [ABSTRACT FROM AUTHOR]

Antipyrine clearance was determined in 41 psoriatics and age-sex matched controls, using sequential measurements of salivary concentration. Antipyrine clearance and elimination rate constant were less in psoriatics (P less than 0.05) and apparent volumes of distribution were similar. These differences were greater between female psoriatics and controls (P less than 0.025; P less than 0.05) and the differences between male psoriatics and controls were not significant. Correlation of simultaneous measurements of saliva and plasma antipyrine concentration in six psoriatics and age-sex matched controls showed no differences between the two groups. We conclude that antipyrine clearance is reduced in psoriasis but the underlying mechanism is unclear. [ABSTRACT FROM AUTHOR]

The activity of aryl hydrocarbon hydroxylase (AHH) in monocytes from 13 healthy control subjects and in 16 patients with discoid psoriasis was measured. The mean basal monocyte AHH activities of the control and psoriatic groups were 3.4 +/- 0.47 and 4.46 +/- 0.55 respectively (pmol 3-OHBP h-1 10(-6) cells). This difference was not significant. The mean induced monocyte AHH activities in the control and psoriatic groups were 56.4 +/- 10.8 and 77.8 +/- 16.0 pmol 3-OHBP h-1 10(-6) cells respectively but this difference was not significant. The mean induction ratios in the control and psoriatic groups were 16.5 +/- 1.8 and 20.4 +/- 3.6 respectively. Again, this difference was not significant. We conclude therefore, that monocyte aryl hydrocarbon hydroxylase activity is not reduced in psoriasis. [ABSTRACT FROM AUTHOR]

The topical effect of the histamine H1-receptor antagonist dimethindene maleate on the wealing response to intradermal histamine, compound 48/80 and house dust mite antigen was studied in 16 subjects using a double-blind procedure. The mean reduction in weal area +/- s.e. mean was 44% +/- 13%, 43% +/- 13% and 31% +/- 13% for histamine, 48/80 and antigen respectively. We conclude that dimethindene maleate is a moderately potent H1-receptor antagonist, and that the inhibition of the 48/80 and house dust mite induced weals is accounted for by the antihistaminic effect of dimethindene maleate. [ABSTRACT FROM AUTHOR]

Aim: There is concern that the provision of the clinical high risk for psychosis (CHR) label is stigmatizing. Prior research suggests people have nuanced reactions to feedback involving the CHR label, including a positive experience receiving feedback and improvement in negative emotions (e.g., shame), while also exhibiting concerns about self-perception and perceptions from others related to the label. The current pilot study aimed to evaluate whether individuals at CHR showed changes in emotional and stigma-related experiences following a CHR psychoeducation intervention, BEGIN: Brief Educational Guide for Individuals in Need., Method: Participants at CHR (N = 26) identified via the Structured Interview for Psychosis-Risk Syndromes completed the Mental Health Attitudes Interview measuring symptom-related and CHR label-related stigma at pre- and post-intervention., Results: Stigma did not increase and participants had greater positive emotions (e.g., feeling hopeful and relieved), post-BEGIN., Conclusion: This study suggests that standardized CHR psychoeducation does not increase stigma in individuals at CHR., (© 2024 John Wiley & Sons Australia, Ltd.)

The ryanodine receptor 1 (RYR1) is a calcium release channel essential for excitation-contraction coupling in the sarcoplasmic reticulum of skeletal muscles. Dominant variants in the RYR1 have been well associated with the known pharmacogenetic ryanodinopathy and malignant hyperthermia. With the era of next-generation gene sequencing and growing number of causative variants, the spectrum of ryanodinopathies has been evolving with dominant and recessive variants presenting with RYR1-related congenital myopathies such as central core disease, minicore myopathy with external ophthalmoplegia, core-rod myopathy, and congenital neuromuscular disease. Lately, the spectrum was broadened to include fetal manifestations, causing a rare recessive and lethal form of fetal akinesia deformation sequence syndrome (FADS)/arthrogryposis multiplex congenita (AMC) and lethal multiple pterygium syndrome. Here we broaden the spectrum of clinical manifestations associated with homozygous/compound heterozygous RYR1 gene variants to include a wide range of manifestations from FADS through neonatal hypotonia to a 35-year-old male with AMC and PhD degree. We report five unrelated families in which three presented with FADS. One of these families was consanguineous and had three affected fetuses with FADS, one patient with neonatal hypotonia who is alive, and one individual with AMC who is 35 years old with normal intellectual development and uses a wheelchair. Muscle biopsies on these cases demonstrated a variety of histopathological abnormalities, which did not assist with the diagnostic process. Neither the affected living individuals nor the parents who are obligate heterozygotes had history of malignant hyperthermia., (© 2019 Wiley Periodicals, Inc.)

The P2X3 receptor subunit, a member of the P2X family of ATP-gated ion channels, is almost exclusively localized in sensory neurons. In the present study, we sought to gain insight into the role of P2X3 and P2X3-containing neurons in sensory transmission, using immunohistochemical approaches. In rat dorsal root ganglia (DRG), P2X3-immunoreactivity (-ir) was observed in small- and medium-sized neurons. Approximately 40% of DRG neuronal profiles in normal rats contained P2X3-ir. In rats that had received neonatal capsaicin treatment, the number of P2X3-positive neurons was decreased by approximately 70%. Analysis of the colocalization of P2X3-ir with cytochemical markers of DRG neurons indicated that approximately 94% of the P2X3-positive neuronal profiles were labelled by isolectin B4 from Bandeiraea simplicifolia, while only 3% contained substance P-ir, and 7% contained somatostatin-ir. In dorsal horn of rat spinal cord, P2X3-ir was observed in the inner portion of lamina II and was reduced subsequent to dorsal rhizotomy, as well as subsequent to neonatal capsaicin treatment. Finally, P2X3-ir accumulated proximal to the site of sciatic nerve ligation, and was seen in nerve fibres in skin and corneal epithelium. In summary, our results suggest that P2X3 is expressed by a functionally heterogeneous population of BSI-B4-binding sensory neurons, and is transported into both central and peripheral processes of these neurons.

1 Aryl hydrocarbon hydroxylase (AHH), a mixed-function oxidase system, has been identified in microsomal preparations of adult breast skin and foreskin. 2 Separation of dermis from epidermis by stretching, showed that AHH activity in human skin is almost exclusively located within the epidermis. 3 Preincubation of whole chopped skin with benzanthracene (5 muM to 100 muM) using a tissue culture system was accompanied by a concentration dependent increase in AHH activity. 4 Although there was no significant difference in AHH activity between the two sites, individuals differed markedly from one another in activity at any one site. Activity was observed to be positively correlated with age.