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J D Lundgren

Publications and source records attributed to J D Lundgren.

At least 163 records · Page 9Linked to original sources
PubMed1990

Gastrin-releasing peptide stimulates glycoconjugate release from feline trachea.

The effect of gastrin-releasing peptide (GRP) on respiratory glycoconjugate (RGC) secretion was investigated in a feline tracheal organ culture model. RGC secretion was stimulated by GRP in a dose-dependent fashion at concentrations from 10(-8) to 10(-5) M (range 15-38% increase above control) with a peak effect within 0.5-1 h of incubation. GRP-(14-27), the receptor binding portion of GRP, and the related molecule, bombesin, also stimulated RGC secretion by approximately 20% above control. Acetyl-GRP-(20-27) stimulated RGC release by 10%, whereas GRP-(1-16) was inactive. Autoradiographic studies with 125I-GRP revealed that specific binding was restricted to the submucosal glands and the surface epithelium. A specific radioimmunoassay showed the content of GRP in feline trachea after extraction with ethanol-acetic acid to be 156 +/- 91 fmol/g wet wt. Indirect immunohistochemistry indicated that ganglion cells located just outside the cartilage contained GRP-immunoreactive materials. GRP is a novel mucus secretagogue that may participate in regulating airway mucosal gland secretion.

Animals↗
PubMed1990

Calcitonin gene-related peptide in human nasal mucosa.

To explore the potential range of functions for calcitonin gene-related peptide (CGRP) in human mucosa, we quantified human inferior turbinate nasal mucosal CGRP content by radioimmunoassay, localized CGRP-immunoreactivity by immunohistochemistry, detected 125I-CGRP binding sites by autoradiography, and tested the ability of CGRP to induce submucosal gland secretion in short-term explant culture of human nasal mucosa. Nasal mucosa contained 0.45-0.54 pmol CGRP/g wet wt (n = 18). Immunoreactive CGRP was found in nerve fibers that densely innervated the walls of small muscular arteries arterioles. Venules and venous sinusoids were innervated by individual CGRP staining fibers. Occasional CGRP-containing nerve fibers were also noted adjacent to submucosal gland acini, near the epithelial basement membrane, and between epithelial cells. Specific 125I-CGRP binding sites were concentrated on small muscular arteries and arterioles. CGRP (4 microM) did not stimulate glycoconjugate or lactoferrin release from mucosal explants. These results indicate that in the human nasal mucosa, CGRP is present in nerve fibers, which most likely represent nociceptive sensorimotor nerves that innervate vascular structures (muscular arteries, arterioles, veins and venous sinusoids). It is likely that CGRP release from sensory neurons may play a role in the regulation of vasomotor responses, but no evidence for a role of CGRP in glandular secretion was found.

Calcitonin Gene-Related Peptide↗
PubMed1990

Bradykinin and respiratory mucous membranes. Analysis of bradykinin binding site distribution and secretory responses in vitro and in vivo.

Bradykinin (BK) and lysyl-BK (lys-BK, kallidin) have been proposed as potentially important mediators of rhinorrhea. Possible mechanisms by which BK might contribute to rhinorrhea were investigated by several approaches. (1) The autoradiographic distribution of 125I-BK binding sites in human inferior turbinate nasal mucosa was determined. (2) The effects of BK and lys-BK and antagonists on radiolabeled respiratory glycoconjugate (RGC) release from human nasal mucosa was measured. (3) The secretory effects of BK were studied in cat tracheal mucosa maintained in short-term explant culture, and in ferret trachea maintained in Ussing chambers. (4) The effects of BK on macromolecule secretion in guinea pig nasal mucosa was studied in vivo. Autoradiographic examination of human nasal mucosa revealed that 125I-BK specifically bound to small muscular arteries, venous sinusoids, and submucosal fibers. No specific binding to submucosal glands or goblet cells was noted. Human nasal fragments secreted significantly increased amounts of RGC in response to 10 microM BK (15.0% +/- 1.8 compared with control values; mean +/- standard error of the mean; n = 7; p less than 0.01 by Student's unpaired t test), 10 microM lys-BK (12.2% +/- 3.3; n = 5; p less than 0.05), and 100 microM methacholine (35.7% +/- 2.3; p less than 0.0001). The addition of 1 microM BK, or 1 microM lys-BK, did not induce release. The addition of the BK receptor antagonist des-Arg9-[Leu8]-BK (10 microM) or inhibition of arachidonic acid metabolism with 50 microM nordihydroguaiaretic acid or 65 microM ibuprofen inhibited the prosecretory effect of 10 microM BK.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1990

Neuropeptide Y (NPY) in human nasal mucosa.

Neuropeptide Y (NPY), a potent vasoconstrictor peptide found in sympathetic neurons, was analyzed in human inferior turbinate nasal mucosal tissue. NPY content determined by radioimmunoassay was 3.13 +/- 0.79 pmol/g tissue (n = 6) in mucosa extracted with ethanol-acetic acid. NPY-immunoreactive nerves were found around small muscular arteries, arterioles, arteriovenous anastomoses, and as free fibers near arteriolar and venous vessels. They formed a plexus around the arterial vessels, and were also present between vascular smooth muscle cells. Few NPY fibers were present near glands or the epithelium. [125I]NPY binding sites were localized by autoradiography to small muscular arteries, arterioles, and a few venous sinusoids. In explant culture experiments, 4 microM NPY did not stimulate release of [3H]glucosamine-labeled glycoconjugates or lactoferrin (a product of serous cells) from nasal mucosal fragments. Degradation of NPY by a tissue homogenate was rapid (t1/2 = 13.5 +/- 2.3 min). The degradation was inhibited by thiorphan and phosphoramidon, inhibitors of neutral endopeptidase activity. NPY released from sympathetic neurons may play a role as a constrictor of arterial vessels and regulate vasomotor tone in the human nasal mucosa.

Arteries↗
PubMed1990

Gastrin-releasing peptide in human nasal mucosa.

Gastrin-releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, was studied in human inferior turbinate nasal mucosa. The GRP content of the mucosa measured by radioimmunoassay was 0.60 +/- 0.25 pmol/g tissue (n = 9 patients; mean +/- SEM). GRP-immunoreactive nerves detected by the immunogold method of indirect immunohistochemistry were found predominantly in small muscular arteries, arterioles, venous sinusoids, and between submucosal gland acini. 125I-GRP binding sites determined by autoradiography were exclusively and specifically localized to nasal epithelium and submucosal glands. There was no binding to vessels. The effects of GRP on submucosal gland product release were studied in short-term explant culture. GRP (10 microM) significantly stimulated the release of the serous cell-specific product lactoferrin, and [3H]glucosamine-labeled glycoconjugates which are products of epithelial goblet cells and submucosal gland cells. These observations indicate that GRP released from nerve fibers probably acts on glandular GRP receptors to induce glycoconjugate release from submucosal glands and epithelium and lactoferrin release from serous cells, but that GRP would probably not affect vascular permeability.

Autoradiography↗
PubMed1990

Vasoactive intestinal peptide in human nasal mucosa.

Vasoactive intestinal peptide (VIP), which is present with acetylcholine in parasympathetic nerve fibers, may have important regulatory functions in mucous membranes. The potential roles for VIP in human nasal mucosa were studied using an integrated approach. The VIP content of human nasal mucosa was determined to be 2.84 +/- 0.47 pmol/g wet weight (n = 8) by RIA. VIP-immunoreactive nerve fibers were found to be most concentrated in submucosal glands adjacent to serous and mucous cells. 125I-VIP binding sites were located on submucosal glands, epithelial cells, and arterioles. In short-term explant culture, VIP stimulated lactoferrin release from serous cells but did not stimulate [3H]glucosamine-labeled respiratory glycoconjugate secretion. Methacholine was more potent than VIP, and methacholine stimulated both lactoferrin and respiratory glycoconjugate release. The addition of VIP plus methacholine to explants resulted in additive increases in lactoferrin release. Based upon the autoradiographic distribution of 125I-VIP binding sites and the effects on explants, VIP derived from parasympathetic nerve fibers may function in the regulation of serous cell secretion in human nasal mucosa. VIP may also participate in the regulation of vasomotor tone.

Cells, Cultured↗
PubMed1990

Indication for fiberoptic bronchoscopy in HIV-infected patients suspected for Pneumocystis carinii pneumonia.

During a six-month period, 40 consecutive fiberoptic bronchoscopic procedures including bronchoalveolar lavage, bronchial brushing and forceps biopsy were performed in local anaesthesia on 34 HIV-infected males presenting symptoms compatible with Pneumocystis carinii pneumonia. In 23 examinations, P. carinii was found. Sixteen examinations were non-diagnostic and one was unsuccessful. The clinical course confirmed the diagnoses of the P. carinii positive as well as the P. carinii negative patients. Except for a lower total lymphocyte count in the patients harbouring P. carinii, the two groups did not differ with regard to history, clinical examination, immunology, serology or chest radiograph. We conclude that fiberoptic bronchoscopy should be performed on wide indications in HIV-infected patients with symptoms compatible with P. carinii pneumonia. The procedure is easily performed, it is safe, and it is highly sensitive. The advantage of an early diagnosis compensates for a rather high frequency of negative examinations.

Adult↗
PubMed1989

The whole-mount method as a technique for measuring experimental changes in airway goblet cell number.

The whole-mount staining method for mucous membranes was introduced as an experimental technique for measuring goblet cell density and for estimating the degree of goblet cell hyperplasia in the trachea of experimental animals. By this technique it was demonstrated that a single intratracheal instillation of lysed extract from human neutrophilic granulocytes in rats after 3 weeks caused a three-fold increase in the density of tracheal goblet cells as compared to control animals receiving saline. The increase is of 3-6 times greater magnitude than previously reported in similar experiments where the number of goblet cells was calculated from cross sections in a traditional manner. It was further shown that the increase in goblet cell density could be prevented if prednisone was given to the animals prior to and during the experiment. It is concluded that the whole-mount preparation method is a useful tool in the quantitation of airway goblet cells in experimental settings, and that it appears to be a more sensitive method than the traditionally used cross section techniques.

Animals↗
PubMed1989

The outcome of Pneumocystis carinii pneumonia in Danish patients with AIDS.

A total of 100 consecutive patients with AIDS were evaluated for efficacy and safety of treatment and secondary prophylaxis directed against Pneumocystis carinii pneumonia (PCP). 89 episodes of PCP were recorded in 75 patients. 63 of the 75 patients (84%) with a first episode of PCP were discharged. Of 72 patients with a first episode of PCP who were initially treated with trimethoprim-sulfamethoxazole. 76% completed therapy successfully. Side effects were common, but generally mild and tolerated during continued treatment. 7/11 patients (64%) with a first episode of PCP who required mechanical ventilation were discharged. Long term prognosis for these patients was not worse than for patients who did not require mechanical ventilation. Relapse of PCP occurred in 3/50 patients (6%) during secondary prophylaxis, 160 mg trimethoprim and 800 mg sulfamethoxazole (TMP-SMZ) every 24 h, compared to 11/16 (69%) patients who were not receiving prophylaxis (p less than 0.00001). No patients discontinued prophylaxis because of side effects. It is concluded that for most patients with AIDS and PCP, treatment and secondary prophylaxis with TMP-SMZ is safe and effective.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Substance P receptor-mediated secretion of respiratory glycoconjugate from feline airways in vitro.

The effect of substance P (SP) and other tachykinins on respiratory glycoconjugate (RGC) release was studied in a feline tracheal organ culture system. SP in concentrations of 10(-5) and 10(-6) M stimulated an increase in RGC release of 35 +/- 8% and 18.5 +/- 5%, respectively. The addition of the protease inhibitor aprotinin or the enkephalinase inhibitor thiorphan to the cultures had no effect on the baseline secretion of RGC but markedly potentiated the activity of SP. SP in the presence of aprotinin or thiorphan was active at 10(-8) -10(-9) M concentrations and was more potent at each concentration studied (in the presence of peptidase inhibitors). Among other tachykinins studied, only physalaemin in the presence of aprotinin had a clear stimulatory effect on RGC release at 10(-6) M concentration (26% +/- 5% increase above control, n = 4, p less than 0.02); kassinin, neurokinin A, and neurokinin B had little or no effect on RGC secretion in concentrations of 10(-6) M or less. Autoradiographic studies of [125I]SP binding revealed SP receptor expression in the submucosal glands of the feline trachea. [125I]SP binding was inhibited in the presence of excess unlabeled SP. We conclude that SP receptors are present in the feline tracheal submucosal glands and that binding to SP receptors results in RGC secretion.

Animals↗
PubMed1989

Pulmonary disease in patients with human immunodeficiency virus infection.

Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi's sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Dexamethasone inhibits respiratory glycoconjugate secretion from feline airways in vitro by the induction of lipocortin (lipomodulin) synthesis.

The effect of glucocorticoids on respiratory glycoconjugate (RGC) secretion was studied in a cat tracheal organ culture system. Dexamethasone (10(-5) to 10(-9) M) added to culture medium for 24 h caused a dose-related reversible inhibition of RCG of as much as 40% with a peak effect at 24 to 60 h after initiation of dexamethasone treatment. A monoclonal antilipocortin antibody added to the cultures blocked the inhibitory effect of dexamethasone on RGC secretion and accelerated the reversal of the dexamethasone effect after discontinuation of dexamethasone treatment. A control antibody without antilipocortin activity had no effect on RGC secretion or dexamethasone-induced inhibition of RGC secretion. Measurement of the concentration of lipocortin in airways revealed a 220% increase after treatment with dexamethasone for 24 h. We conclude that dexamethasone inhibits RGC secretion through the induction of lipocortin synthesis.

Animals↗
PubMed1988

Dexamethasone reduces rat tracheal goblet cell hyperplasia produced by human neutrophil products.

An experimental model leading to goblet cell hyperplasia was developed in order to examine the possible preventive effects of glucocorticosteroids. Human peripheral blood neutrophils were isolated and either freeze-thaw lysed or activated with serum opsonized zymosan. Supernatants from these neutrophil preparations were then instilled transorally into the tracheas of male Sprague-Dawley rats. After 7-35 days, the rats were sacrificed; the lower tracheas were excised, fixed in formalin, and stained with periodic acid-Schiff and alcian blue; and the goblet cells and total epithelial cells were counted. Supernatants from both lysed neutrophils and zymosan-activated neutrophils stimulated a 50% and 42% (respectively) increase in goblet cells after 3 weeks as compared to controls. Purified human neutrophil or porcine pancreatic elastase also caused goblet cell hyperplasia, while sham challenge, challenge with buffer, or challenge with lysates of human mononuclear cells failed to affect goblet cell number. The increase in goblet-cell number was maximal by three weeks and persisted through 35 days. Treatment of animals with glucocorticosteroids administered by the addition of dexamethasone to the drinking water (2 mg/l for 1 week followed by 0.2 mg/l for 2 weeks) ablated the goblet cell hyperplasia produced by neutrophil lysates or elastase alone. We conclude that goblet cell hyperplasia may be induced with insufflated neutrophil products and that this action can be inhibited by treatment with corticosteroids.

Animals↗
PubMed1985

The role of eicosanoids in respiratory mucus hypersecretion.

The role of eicosanoids in the excessive secretion of respiratory mucous glycoproteins (MGP) accompanying immediate hypersensitivity and inflammatory pulmonary states has only been addressed in the last few years. Three lines of evidence suggest that eicosanoids may participate in the physiologic regulation of MGP secretion as well as being capable of stimulating increased MGP production. First, inhibition of eicosanoid generation with corticosteroids or eicosatetraynoic acid (ETYA) reduces ongoing baseline MGP secretion while selective inhibition of prostaglandin production with nonsteroidal anti-inflammatory agents increases MGP release. Second, arachidonic acid and a variety of eicosanoids stimulate MGP secretion in vitro. In fact, several lipoxygenase pathway metabolites including hydroxyeicosatetraenoic acids (HETEs) and leukotrienes (LTC4 and LTD4) significantly increase MGP secretion in nanogram quantities. Third, a variety of pulmonary cells including airway epithelium, endothelial cells, mast cells, alveolar macrophages and neutrophilic leukocytes generate eicosanoids under conditions that would be encountered in clinical states in which mucus secretion occurs. Thus, mucus secretion during both normal and stimulated states would be influenced by eicosanoids. It seems likely that this eicosanoid-mucus secretion relationship is very important in all forms of asthma, but most particularly in aspirin-related asthma.

Animals↗