L-Ala-substituted rat galanin analogs distinguish between hypothalamic and jejunal galanin receptor subtypes

In order to explore which amino acids or which blocks of amino acids in the 29 amino acid neuropeptide galanin are important for recognition of the endogenous ligand by galanin receptor subtypes present in the jejunum and in the hypothalamus, respectively, we have carried out L-Ala substitutions of individual amino acids or of blocks of amino acids in the rat galanin sequence and examined the binding of the obtained analogs to the rat hypothalamic and jejunal galanin receptor subtypes. This study reveals that the galanin sequence YLLGPH^9–14 is essential for recognition of galanin by both the rat hypothalamic and jejunal galanin receptor subtypes. Substitution of the N-terminal amino acids, GWTL^1–4, leads to total loss of affinity of galanin for both hypothalamic and jejunal galanin receptors. The α-helical C-terminal amino acid (25–29) part of galanin has no greater influence on the affinity of galanin to the hypothalamic galanin receptor subtype. L-Ala substitution of the C-terminal amino acids of galanin KHGLT^25–29 shows, however, that this C-terminal motif is essential for the recognition by the jejunal galanin receptor subtype, whereas amino acids in the middle portion of galanin NSAG^5–8 are of importance for binding to the hypothalamic but not to the jejunal receptor. [Ala^5–8] Galanin thus has a more than 100-fold higher affinity to jejunal receptor than to the hypothalamic receptor, while [Ala^25–29] galanin has a more than 100-fold higher affinity for the hypothalamic than for jejunal galanin receptor subtypes. pH dependence of the galanin binding to these receptor subtypes is also different. © Munksgaard 1997.     

Increased carbon monoxide levels in the nasal airways of subjects with a history of seasonal allergic rhinitis and in patients with upper respiratory tract infection

BACKGROUND: Carbon monoxide (CO) has emerged as an endogenously produced gaseous mediator known to be involved in bronchial smooth muscle regulation. Increased amounts of CO have been found in exhaled air during asthma and lower airway inflammation. Recently CO has been shown to be produced in the nasal airways, but there are no reports of altered CO levels in nasal airways during inflammation. OBJECTIVE: This study was designed to investigate if CO levels increase in the human nasal airways during inflammatory conditions, such as allergy and upper airway respiratory tract infection (URTI). METHODS: CO was sampled separately from the upper and lower airways of 13 healthy control subjects, six patients with a history of allergic rhinitis and six patients with URTI. RESULTS: Nasal CO levels were increased in subjects with allergic rhinitis, compared to healthy controls (2.07 +/- 0.15 ppm, n = 6 and 1.62 +/- 0.08 ppm, n = 13, respectively, P < 0.01). CO levels were also increased in patients with URTI, compared to the same controls (1.92 +/- 0.09 ppm, n = 6, P < 0.05). Normal levels of CO were found in air from the lower airways among subjects with allergic rhinitis, whereas corresponding levels in the URTI patients were increased. CONCLUSION: The present data demonstrates that upper airway CO levels increase in parallel with different inflammatory stimuli, such as allergy and infection, suggesting a role for CO as marker or mediator of nasal inflammation.     

Primary stimulation of CD4+ cells in the presence of IL-4 or IFN-gamma alters the frequencies of cytokine-producing cells at restimulation.

The induction of specific effector functions in naive T cells may be directed by accessory signals during activation. These could be elicited through binding to cell surface molecules or through factors secreted by antigen-presenting cells or other simultaneously activated cells. We have investigated the influence of CD8+ cells and of exogenously added cytokines (interleukin (IL)-2, IL-4 and interferon (IFN)-gamma) on the cytokine production in splenic CD4+ T cells. IL-2, IL-4, IL-5 and IFN-gamma production in CD4+ cells was measured at the single cell level during primary mitogen stimulation in vitro in the presence or absence of factors or CD8+ cells. On day 5 the cells were restimulated with mitogen alone and analysed to evaluate the short-term development of cytokine-producing cells in such cultures. Preactivation in the presence of either exogenous IL-4 or IFN-gamma led to an increased production of IL-4 and IFN-gamma respectively at restimulation, and the effects of both IL-4 and IFN-gamma were augmented by IL-2. After preactivation in the presence of IL-2 and IL-4, every third CD4+ cell could be induced to produce IL-4. Exogenous IL-4 or IFN-gamma further decreased each other's production. Depletion of CD8+ cells before activation resulted in a slight increase of IL-4-producing cells, indicating that simultaneous activation of CD8+ cells will influence lymphokine production in CD4+ cells. The results suggest that the pattern of lymphokines induced in naive cells may be influenced by factors secreted by preactivated CD4+ and CD8+ cells, and that naive cells are preferentially 'recruited' to produce similar cytokines.     

Health Experience of Compressed Air Workers during Construction of the Mass Transit Railway in Hong Kong

This paper reports the health experience of compressed air workersduring construction of the Island Line Section of the Mass TransitRailway in Hong Kong. The requirements of CIRIA's Code of Practiceincluding specifications of the Blackpool Tables for decompressionprocedures and the employment of doctors to monitor the healthof exposed workers by regular examination were prescribed bylocal legislation. Over a 3 year period there were 394 716 man-decompressionsfrom pressures between 1 and 3-5 kg/cm² with 2032 cases of acutedecompression sickness giving a bends rate of 0-52 per cent.The epidemiology followed the usual pattern of increase in bendsrate with increase in pressure and length of shift and withage. Most attacks occurred within a short period after decompressionand the majority of limb pains affected the leg. There werealso 10 cases of barotrauma and 22 cases of dysbaric osteonecrosisof which 7 resulted in some disability. The low incidence ofillness was an index of the effectiveness of the Code of Practiceas applied to a large scale compressed air work operation butthe toll of dysbarism, albeit small, underlines the problemthat there are as yet no decompression procedures which willprotect all men at all times and indicates the need for furtherresearch and work-site evaluation. Requests for reprints should be addressed to: W. K. Lo, Occupational Health Division, Labour Department Headquarters, Harbour Building, 38 Pier Road, Central Hong Kong.     

Localized pachydermodactyly in tuberous sclerosis

Pachydermodactyly refers to a rare form of digital fibromatosis involving the proximal portions of the fingers. There are only nine cases reported in the literature, ill idiopathic and occurring in young men. We report a 5-year-old Chinese boy with tuberous sclerosis who presented with localized pachydermodactyly since birth. This congenital form of pachydermodactyly may represent an additional cutaneous sign of tuberous sclerosis.     

Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B-related cirrhosis

Abstract Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B-related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 μg/h, following a bolus injection of 250 μg. In systemic haemodynamics, the mean arterial pressure (MAP) increased ( P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P = 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion ( P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min ( P = 0.057) and 30 min ( P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus-related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.     

Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps

BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.     

Allergen-reactive antibodies are found in nasal fluids from patients with birch pollen-induced intermittent allergic rhinitis,but not in healthy controls

BACKGROUND: Increased levels of allergen-reactive immunoglobulins (Igs) have been reported in nasal fluids from patients with intermittent allergic rhinitis (IAR) sensitive to ragweed and grass. The aims of this study were to make a detailed characterization of nasal fluid Igs in birch pollen-induced IAR. METHODS: Nasal fluids were obtained from 23 patients with birch pollen-induced IAR during and after the birch pollen season, and from 20 healthy controls. Nasal fluid total and Bet v 1-reactive (IgA), IgE and IgG as well as albumin were analyzed by immunoassays. The integrity of IgA and IgG, and the molecular form of IgA were assessed by Western blotting and column fractionation, respectively. RESULTS: Nasal fluid total IgE and IgG, but not IgA, were higher in patients compared with controls. Western blotting indicated no significant degradation of IgA (including S-IgA) and IgG. Most of the IgA, including Bet v 1-reactive antibodies, was of the secretory form and of the IgA1 subclass. Bet v 1-reactive IgA and IgG were present in all patients, but was mostly nondetectable in controls. No significant differences in the levels of Bet v 1-reactive IgA and IgG were found in patients during the birch pollen season compared with off season. Both Bet v 1 and Bet v 2-reactive IgE were nondetectable in most samples. CONCLUSIONS: Nasal fluid Bet v 1-reactive IgA and IgG were found in all patients with birch pollen-induced IAR, but not in controls. However, no significant differences were found between patients during and after the birch pollen season.