House-dust-mite allergen (Der p 1) levels in university colleges

BACKGROUND: In coastal Australia, mean house-dust-mite allergen concentration is 20-40 times higher in homes than in public buildings. Allergen concentrations in university colleges, which share some characteristics of both homes and public buildings, are not known. The study aimed to compare bed mite-allergen concentration in colleges with local homes. METHODS: Mattress dust was collected from three colleges (n = 60 in each) and local homes (n = 68) during summer. Der p 1 was measured by ELISA. Information was collected on the floor plan of the colleges, cleaning practices, age of building, and orientation of room. RESULTS: Most college mattresses (94%) had Der p 1 concentrations less than the mean of homes in the same climate. The geometric means of Der p 1 in the mattresses of the colleges were as follows: A, 8.9 micrograms Der p 1/g fine dust (95% CI 6.9, 11.5); B, 1.9 (1.5, 2.3); and C, 1.5 (1.2, 2.0), compared to homes, 22.5 (17.6, 28.7). The percentages of college mattresses with less than 2 micrograms/g were 7%, 48%, and 58%, respectively, compared to 4% for homes. Higher Der p 1 concentrations were weakly associated with age of building in college A, and orientation in college B. Der p 1 concentrations were independent of floor level and age of mattress. CONCLUSIONS: These findings indicate that low allergen concentrations are achievable without extreme hygiene and cleaning measures in a climate which supports mite proliferation in homes.     

Expression cloning of a rat hypothalamic galanin receptor coupled to phosphoinositide turnover

The neuropeptide galanin is widely distributed throughout the central and peripheral nervous systems and participates in the regulation of processes such as nociception, cognition, feeding behavior, and insulin secretion. Multiple galanin receptors are predicted to underlie its physiological effects. We now report the isolation by expression cloning of a rat galanin receptor cDNA distinct from GALR1. The receptor, termed GALR2, was isolated from a rat hypothalamus cDNA library using a 125I-porcine galanin (125I-pGAL) binding assay. The GALR2 cDNA encoded a protein of 372 amino acids exhibiting 38% amino acid identity with rat GALR1. Binding of 125I-pGAL to transiently expressed GALR2 receptors was saturable (KD = 0.15 nM) and displaceable by galanin peptides and analogues in rank order: porcine galanin approximately M32 approximately M35 approximately M40 >/= galanin-(1-16) approximately M15 approximately [D-Trp2]galanin-(1-29) > C7 > galanin-(3-29). This profile resembles that of the rat GALR1 receptor with the notable exception that [D-Trp2]galanin exhibited significant selectivity for GALR2 over GALR1. Activation of GALR2 receptors with porcine galanin and other galanin analogues increased inositol phospholipid turnover and intracellular calcium levels in stably transfected Chinese hamster ovary cells and generated calcium-activated chloride currents in Xenopus oocytes, suggesting that the rat GALR2 receptor is primarily coupled to the activation of phospholipase C.     

Effects of amide and amine plasma-treated ePTFE vascular grafts on endothelial cell lining in an artificial circulatory system

Vitamin A requirement for early embryonic development is clearly evident in the gross cardiovascular and central nervous system abnormalities and an early death of the vitamin A-deficient quail embryo. This retinoid knockout model system was used to examine the biological activity of various natural retinoids in early cardiovascular development. We demonstrate that all-trans-, 9-cis-, 4-oxo-, and didehydroretinoic acids, and didehydroretinol and all-trans-retinol induce and maintain normal cardiovascular development as well as induce expression of the retinoic acid receptor beta2 in the vitamin A-deficient quail embryo. The expression of RARbeta2 is at the same level and at the same sites where it is expressed in the normal embryo. Retinoids provided to the vitamin A-deficient embryo up to the 5-somite stage of development, but not later, completely rescue embryonic development, suggesting the 5-somite stage as a critical retinoid-sensitive time point during early avian embryogenesis. Retinoid receptors RARalpha, RARgamma, and RXRalpha are expressed in both the precardiac endoderm and mesoderm in the normal and the vitamin A-deficient quail embryo, while the expression of RXRgamma is restricted to precardiac endoderm. Vitamin A deficiency downregulates the expression of RARalpha and RARbeta. Our studies provide strong evidence for a narrow retinoid-requiring developmental window during early embryogenesis, in which the presence of bioactive retinoids and their receptors is essential for a subsequent normal embryonic development.     

Antigen receptor engagement delivers a stop signal to migrating T lymphocytes

We investigated the role of the T cell antigen receptor (TcR) in control of T cell migration in an in vitro system. We used T cells from transgenic mice bearing a TcR for the lysozyme peptide 48-62 bound to I-A(k) (3A9). T cells from the 3A9 TcR transgenic mice crawled on purified intercellular adhesion molecule-1 substrates, but strikingly, stopped upon interaction with the physiological ligand, i.e., the mouse I-A(k) with covalently attached hen egg white lysozyme peptide residues 48-62 complex. TcR-triggered stopping was reversible by treatment with adhesion-strengthening phorbol esters. The microtubule organizing center of stopped cells was positioned adjacent to the site of stable cell anchorage. Direct conversion of lymphocyte function associated-1 to the high-affinity conformation with antibodies also stopped T cells in a similar manner to antigen. Thus, physiological TcR engagement triggers a stop signal through lymphocyte function associated-1. We propose that the stop signal is an early and essential event in T cell activation that also will play an important role in control of T cell migration.     

Observations on the effects of aerosolized albuterol in acute asthma

To determine the dose of albuterol required to terminate acute episodes of asthma, 92 acutely ill subjects received three doses of 2.5 mg each by nebulization every 20 min. Peak expiratory flow rates (PEFR) and signs and symptoms were serially monitored. A dose-response increase in pulmonary function was found, but only 66% of the subjects improved sufficiently to be sent home. Of these, 56% required < or = 5.0 mg of drug to reach the discharge threshold, whereas the remainder needed 7.5 mg. In 34% of participants, albuterol was ineffectual. These individuals were characterized by more severe obstruction at presentation, and after three doses of medication their PEFR still did not exceed 40% of the expected value. Further treatment in the emergency department (ED) or hospital was not immediately helpful, and these patients ultimately required 3.8 +/- 0.4 d of inpatient care to become asymptomatic. There were no discernible differences between responders and nonresponders in the type or quantity of medications used. However, the nonresponders had more severe disease as measured by recurrent hospitalizations and ED visits. This study demonstrates that, in emergency situations, albuterol does not relieve acute airway obstruction in all asthmatic individuals with equal efficacy. Two-thirds of patients are sensitive, and in these patients 5 to 7.5 mg of albuterol provides optimal treatment. In the remainder, albuterol, even in high doses, has little effect for days.     

Does alpha-melanocyte-stimulating hormone from the pars intermedia regulate suckling-induced prolactin release? Supportive evidence from morphological and functional studies

Recent evidence suggests that substances derived from the hypophyseal intermediate lobe (IL) play a crucial role in the regulation of suckling-induced PRL secretion. The purpose of the present study was to explore this possibility further by determining whether the suckling stimulus acutely increases the secretory activity of the IL and whether alpha MSH, a major secretory product of the IL, plays a specific role in suckling-induced PRL release. Light microscopic morphometric analysis of serial pituitary sections obtained from lactating rats revealed that as little as 1 min of suckling caused a significant increase in the proportion of the IL that was in secretory configuration (11.8 +/- 0.7% vs. 6.7 +/- 0.5%; 1-min suckled vs. nonsuckled control; mean +/- SE). Moreover, the fraction of the IL in secretory configuration continued to increase after 5 and 10 min of nursing (to 16.0 +/- 0.8% at 5 min and 18.2 +/- 0.7% at 10 min). In contrast, serum PRL was not significantly elevated above the control level after 1 min of suckling (18.1 +/- 13.5 vs. 9.9 +/- 6.5 ng/ml, 1-min suckled vs. control). In fact, a significant rise in PRL levels (to 314.4 +/- 19.4 ng/ml) could be detected only after 10 min of nursing. Thus, secretion by the IL in response to suckling preceded the release of adenohypophyseal PRL, suggesting that a secretory product(s) from the pars intermedia is involved in the modulation of nursing-induced PRL release. Having established a sequential temporal relationship between these two phenomena, we next investigated whether alpha MSH was the IL factor involved in the regulation of suckling-induced PRL secretion. To this end, lactating rats were injected either with antiserum to alpha MSH or preimmune serum and then allowed to nurse their pups. Serial blood samples were taken from the mothers 15, 30, 60, and 90 min after the litters were returned, and serum PRL was measured by RIA. We found that the suckling-induced rise in serum PRL was severely attenuated in animals that received anti-alpha MSH serum. This suppression was most evident at 15 min (70.1 +/- 13.4 vs. 323.5 +/- 127.0 ng/ml, antibody treated vs. preimmune serum control) and persisted throughout the entire 90-min test period. When taken together, our results suggest that suckling-induced PRL secretion is mediated at least in part by alpha MSH released from the hypophyseal IL.