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Notes: Abstract: The adrenergic receptors of rat pineal gland were investigated using radiolabeled ligand binding and photoaffinity labeling techniques. 125I-2-[β-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT) and 125I-cyanopindolol (125I-CYP) labeled specific sites on rat pineal gland membranes with equilibrium dissociation constants (KD) of 48 (±5) pM and 30 (±5) pM, respectively. Binding site maxima were 481 (±63) and 1,020 (±85) fmol/mg protein. The sites labeled by 125I-HEAT had the pharmacological characteristics of α1-adrenergic receptors. 125I-CYP-labeled β-adrenergic receptors were characterized as a homogeneous population of β1-adrenergic receptors. The α1- and β1-adrenergic receptors were covalently labeled with the specific photoaffinity probes 4-amino-6,7-dimethoxy-2-{4-[5-(4-azido-3-[125I]iodo-phenyl) pentanoyl]-1-piperazinyl}quinazoline (125I-APDQ) and 125I-p-azidobenzylcarazolol (125I-pABC). 125I-APDQ labeled an α1-adrenergic receptor peptide of Mr= 74,000 (±4,000), which was similar to peptides labeled in rat cerebral cortex, liver, and spleen. 125I-pABC labeled a single β1-adrenergic receptor peptide with a Mr= 42,000 (±1,500), which differed from the 60–65,000 peptide commonly seen in mammalian tissues. Possible reasons for these differences are discussed.

Notes: Inbred guinea pigs selected for high (IMM/S) respectively low (IMM/R) responsiveness to ovalbumin (OA) as measured by induced respiratory anaphylaxis, were investigated for atopic immune responses of their conjunctival mucosa. IMM/S animals sensitized either by inhalation of OA, or by instillation of antigen into the conjunctival sac, developed regularly an acute ocular inflammatory response to topical (conjunctival) challenge with the allergen. A minimum of 1 μg OA dropped repeatedly into the conjunctival sac was enough for both ocular and systemic sensitization of the animals, but the minimal dose of effective challenge was considerably higher. In IMM/R animals, ocular hypersensitivity was not achieved by inhalation of OA, but after topical administration of the antigen some of the IMM/R strains could be challenged to ocular anaphylactic responses of the same intensity as observed in IMM/S animals. The conjunctivae of both IMM/S and IMM/R animals could be sensitized passively by intraperitoneal injection of guinea pig sera containing homocytotropic antibodies to OA, but topical administration of such sera had no effect.

Notes: The genetic and immunological basis of respiratory anaphylaxis was studied in two strains of guinea pigs selectively bred for either high or low respiratory anaphylactic response to inhalation of ovalbumin. Individuals of the parental strains, Fl-hybrids and backcross offspring were examined for class II MHC type and asthmatic response to ovalbumin. Analysis of the results revealed an association of asthma phenotype and MHC class II type. Apart from the gene(s) in the MHC several other genes seem to be involved in the control of guinea pig asthma.

Notes: A single conjunctival application of ovalbumin to inbred guinea pigs (IMM/S 209) immunized with the same antigen in Freund's complete adjuvant provoked an acute purulent inflammation of the anterior segment of the eyes with a duration of up to 1 week. Intense conjunctival injection and chemosis were followed by a purulent discharge. A corneal haze was observed regularly, and a considerable proportion of the animals developed a pronounced pannus and corneal ulcers. Tear fluid cytology revealed a rapid increase in cell concentration, from the normal level (〈 108/1) to 〉 1011/1.Seventy to 95% of the cells were polymorphonuclear leukocytes. Histological examination revealed an acute inflammatory reaction which radiated from the conjunctival fornices to the entire anterior segments of the eyes. The process was characterized by an intense oedema, vasodilation and perivascular aggregations of polymorphonuclear leukocytes, and to a lesser extent eosinophilic granulocytes which characteristically infiltrated and penetrated the epithelial layers. Ncovascularization could be observed early after challenge in the stroma of all parts of the outer eye. Ulcerations of the conjunctival and corneal epithelia were observed frequently. After a number of reiterations of the antigenic challenge, a marked infiltration with lymphocytes and basophils/mast cells was observed, and significant scarring of the conjunctival mucosa developed. In several animals, a slight, but significant co-reaction of the contra-lateral, non-challenged eye was observed.

Notes: The present paper presents data on the phonetic development of four normal Swedish infants, who were audiorecorded bi-weekly in their homes from 0;1 to 1;5. Our results show five distinct stages in the development of early vocalizations: the glottal stage, the velar/uvular stage, the vocalic stage, the reduplicated consonant babbling stage and the variegated consonant babbling stage. The results are based on auditory analysis of selected parts of the material. A comparison is made of this developmental pattern with studies of infants raised in other linguistic communities. The results of this comparison support the claim that babbling follows a universal developmental pattern.

Notes: The magnitude and duration of dopamine (DA) signaling is defined by the amount of vesicular release, DA receptor sensitivity, and the efficiency of DA clearance, which is largely determined by the DA transporter (DAT). DAT uptake capacity is determined by the number of functional transporters on the cell surface as well as by their turnover rate. Here we show that inhibition of phosphatidylinositol (PI) 3-kinase with LY294002 induces internalization of the human DAT (hDAT), thereby reducing transport capacity. Acute treatment with LY294002 reduced the maximal rate of [3H]DA uptake in rat striatal synaptosomes and in human embryonic kidney (HEK) 293 cells stably expressing the hDAT (hDAT cells). In addition, LY294002 caused a significant redistribution of the hDAT from the plasma membrane to the cytosol. Conversely, insulin, which activates PI 3-kinase, increased [3H]DA uptake and blocked the amphetamine-induced hDAT intracellular accumulation, as did transient expression of constitutively active PI 3-kinase. The LY294002-induced reduction in [3H]DA uptake and hDAT cell surface expression was inhibited by expression of a dominant negative mutant of dynamin I, indicating that dynamin-dependent trafficking can modulate transport capacity. These data implicate DAT trafficking in the hormonal regulation of dopaminergic signaling, and suggest that a state of chronic hypoinsulinemia, such as in diabetes, may alter synaptic DA signaling by reducing the available cell surface DATs.

Notes: Skin diseases have been shown to have a significant adverse impact on the health-related quality of life of patients that may be underestimated by objective assessments of clinical severity. The main aim of this study was to measure the health-state utilities on a scale between 0 (dead) and 1 (full health) of patients with psoriasis and atopic eczema, and to measure the willingness to pay for a cure for psoriasis and atopic eczema. A second aim was to analyse how these measures are related to different dimensions of health-related quality of life, as measured by general and disease-specific quality of life instruments and a subjective measure of disability activity. This study was based on data from a questionnaire administered to, and interviews conducted with, 366 patients with psoriasis and atopic eczema aged 17–73 years, attending the dermatology outpatient clinic in Uppsala, Sweden from November 1996 to December 1997. The survey included: a rating scale question, a time trade-off question, a standard gamble question, a dichotomous choice willingness to pay question, a bidding-game willingness to pay question, a generic quality of life instrument (SF-36), a disease-specific quality of life instrument (the Dermatology Life Quality Index) and a subjective measure of disease activity (on a visual analogue scale). The mean health-state utility was 0·69 (rating scale), 0·88 (time trade-off) and 0·97 (standard gamble) for patients with psoriasis. The corresponding health-state utilities for patients with atopic eczema were 0·73, 0·93 and 0·98. On average, patients were willing to pay between 1253 and 1956 Swedish crowns (SEK) per month for a psoriasis cure and between SEK 960 and 1083 per month for an atopic eczema cure ($1 = SEK 8·25 and £1 = SEK 13·23). The health-state utilities were related to SF-36, the Dermatology Life Quality Index and disease activity in the expected direction and the correlations were strongest for rating scale and weakest for standard gamble. The willingness to pay was correlated with the Dermatology Life Quality Index and disease activity, but not with SF-36. The study indicates that it is feasible to measure health-state utilities and willingness to pay in this patient population, and the sizeable willingness to pay suggests that skin diseases are associated with substantial reductions in quality of life.