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Biomedical subjects

J D Lundgren

Publications and source records attributed to J D Lundgren.

At least 127 records · Page 7Linked to original sources
PubMed1994

Tumour necrosis factor and eicosanoid production from monocytes exposed to HIV in vitro.

We investigated the hypothesis that exposure of monocytes to human immunodeficiency virus (HIV) augments production of proinflammatory mediators. The production of tumour necrosis factor alpha (TNF-alpha) and the eicosanoids PGE2 and LTB4 from human monocytes was evaluated after exposure to two strains of HIV (SSI-002 or HIV-1IIIB). After 16 h incubation with low doses of SSI-002, lipopolysaccharide-stimulated TNF-alpha production was enhanced 70-85% while PGE2 production was decreased. Heat-inactivated virus failed to alter the production of these mediators. Higher viral doses tended to decrease TNF-alpha and PGE2 production concomitantly, but this might be due to toxicity. HIV-1IIIB had no effect on either TNF-alpha or PGE2 production. Calcium ionophore-stimulated LTB4 production was doubled by HIV-1IIIB, but significantly decreased by SSI-002. Three or seven days after exposure to both HIV strains, increased PGE2 production was found. In conclusion, HIV only modestly altered the production of mediators from monocytes. The effects were strain-specific. In most experiments a second stimulus was required to demonstrate differences.

Dinoprostone↗
PubMed1993

Antibody response to a major human Pneumocystis carinii surface antigen in patients without evidence of immunosuppression and in patients with suspected atypical pneumonia.

IgG and IgM antibodies to a purified human Pneumocystis carinii surface antigen (gp95) were measured in 694 serum specimens from two different population groups using an EIA technique. In a population of 441 patients with no evidence of immunosuppression, the percentage of persons positive for IgG antibodies to gp95 was significantly lower in the age group 1 to 9 years (30%, 23/77) compared to persons 10 to 19 years old (56%, 49/88). In the age group 1 to 14 years there was a significant correlation between the percentage of persons with IgG antibodies to gp95 and age. In 106 consecutive patients under evaluation due to atypical pneumonia, 76 patients showed no change in the titre of antibodies to Legionella spp. or Mycoplasma pneumoniae in two consecutive serum samples. Three of these 76 patients (4%) demonstrated an increase in the level of IgG antibodies to gp95 in the paired samples. One of these patients had a verified Pneumocystis carinii pneumonia, and the two others were elderly men in whom no microbiological diagnosis of the pneumonia was established. Thus, it is concluded that IgG antibodies to gp95 develop in the majority of nonimmunosuppressed persons before the age of 13. Furthermore, Pneumocystis carinii pneumonia should be considered in the differential diagnosis in patients suspected of having atypical pneumonia.

Adolescent↗
PubMed1993

Biological properties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection.

OBJECTIVE: To characterize the biological properties of HIV isolates obtained at the time of primary infection, and relate this to the subsequent course of the infection. METHODS: Syncytium-inducing (SI) capacity, tropism for cell lines (MT4 and H9) and replication rate were determined in 49 HIV isolates obtained from 17 HIV seroconverters. Thirteen of the 17 patients had a symptomatic primary HIV infection. Correlation between biological phenotype and clinical progression was analysed. RESULTS: SI isolates were recovered in six patients from the first sample taken during primary infection, non-SI (NSI) isolates only were identified in 10 of the patients and isolation culture was negative in one patient. For all patients from whom SI virus was initially isolated, this phenotype persisted during the follow-up period (range, 17-219 weeks). The duration of fever during primary infection was longer for patients with SI isolates than for patients with NSI isolates (P = 0.05). Both types of isolates were associated with a significant fall in CD4 lymphocytes during follow-up (P < 0.05). Patients with SI isolates developed HIV-related immune deficiency more rapidly than patients with NSI isolates (P < 0.05). CONCLUSIONS: The biological phenotype of HIV strains isolated during the time of seroconversion may be an important determinant of the subsequent course of the infection.

CD4-Positive T-Lymphocytes↗
PubMed1993

Effects of gastrin-releasing peptide and analogues on guinea pig nasal mucosal secretion.

The effects of gastrin-releasing peptide (GRP), bombesin, GRP-(1-16) and GRP-(21-27) on guinea pig nasal mucosal secretion were studied in vivo. GRP, bombesin, and GRP-(21-27) induced significant secretion of total protein, albumin, and alkaline phosphatase. GRP induced significant secretion at lower concentrations (10(-11) and 10(-10) M) than were required for bombesin and GRP-(21-27) (10(-7) M). GRP-(1-16) did not stimulate secretion, indicating that the COOH-terminal region of GRP contained the secretagogic principle. Capsaicin, a stimulant of nociceptive sensory nerves, stimulated GRP release into nasal secretions. These data suggest that GRP is present in guinea pig nasal mucosa and that the COOH-terminal region of GRP may regulate mucosal macromolecule secretion.

Animals↗
PubMed1993

Serum type III procollagen peptide in patients with Pneumocystis carinii infection. The Copenhagen-Amsterdam PCP-Prednisolone Study Group.

Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders. To investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid [CS] group and 22 in control group). All patients were treated with co-trimoxazole. In the control group, PIIINP serum levels at day of initiation of therapy (Day 0) were significantly higher in patients requiring mechanical ventilation and/or dying during the course of the pneumonia, and serum levels of PIIINP higher than 5 ng/ml were associated with a higher mortality than levels below 5 ng/ml. The level of PIIINP increased from Day 0 to Day 5. There was a significant correlation between changes in PIIINP levels and changes in the alveolar-arterial oxygen gradient from Day 0 to Day 5. In the CS group, the PIIINP levels decreased while steroid was administered. At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups. PIIINP serum levels may predict the clinical outcome of PCP. The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure. CS prevents this increased inflammatory activity.

AIDS-Related Opportunistic Infections↗
PubMed1993

Amount of Pneumocystis carinii and degree of acute lung inflammation in HIV-associated P carinii pneumonia.

Correlations between semiquantitative amounts of Pneumocystis carinii (PC), the degree of inflammation, and the severity of pneumonia were analyzed in 58 patients with PC pneumonia (PCP). Material from both transbronchial biopsies (TBBs; n = 39) and bronchoalveolar lavage fluid (BALF; n = 57) was examined. In the TBB the amount of PC correlated strongly with overall inflammation in the interstitium (Kendall correlation coefficient [Kcc] = 0.59; p < 0.0001), type 2 pneumocyte proliferation, and edema formation. The amount of PC in the TBB also correlated with interstitial accumulation of neutrophils (Kcc = 0.54; p = 0.0001), lymphocytes, and macrophages. In BALF the amount of PC correlated with edema formation and type 2 pneumocyte proliferation in the TBB but not with the percentage of neutrophils, lymphocytes, or macrophages in BALF. The amount of PC in the BALF and the percentage of neutrophils in the BALF correlated significantly with Po2 and the serum lactate dehydrogenase (LDH) level. Neither short-term nor long-term survival was affected by the amount of PC, inflammatory markers in the TBB, inflammatory cells in BALF, Po2, or the serum LDH levels. In conclusion, the amount of PC is associated with the extent of the acute inflammatory reaction in the lung in PCP associated with human immunodeficiency virus (HIV).

Adult↗
PubMed1993

IgM response to a human Pneumocystis carinii surface antigen in HIV-infected patients with pulmonary symptoms.

We have developed an ELISA to detect IgM antibodies to a major human Pneumocystis carinii surface antigen (gp95), and investigated the IgM response in 128 HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Only 5 (4%) patients had IgM antibodies to P. carinii gp95. Four of the 5 patients with IgM antibodies also had IgG antibodies to gp95 and microbiologically proven P. carinii pneumonia (PCP). In 76/128 patients for whom serial samples were available, changes in antibody response were determined. In 3 patients we demonstrated an increase in IgM antibody response to gp95. These patients also showed an increase in IgG antibodies to gp95 and had microbiologically proven PCP. Prior to the development of the IgM response, IgG antibodies to gp95 were detectable in all 3 patients. Thus, HIV-infected patients with PCP seldom produce IgM antibodies to the major human P. carinii surface antigen. The increase in IgM response during the course of PCP observed in 3 patients suggests either reinfection with a new strain, or antigenic drift of an already acquired strain of P. carinii.

AIDS-Related Opportunistic Infections↗
PubMed1992

Improved diagnosis of Pneumocystis carinii infection by polymerase chain reaction on induced sputum and blood.

Detection of Pneumocystis carinii by the polymerase chain reaction (PCR) may facilitate non-invasive diagnosis of P carinii pneumonia and study of its epidemiology. We have compared the sensitivity and specificity of two PCR methods with those of conventional staining for detection of P carinii in induced sputum, bronchoalveolar lavage fluid (BAL), and blood. Of 71 sputum samples, 17 were from patients with microbiologically confirmed P carinii pneumonia. A nested PCR method correctly identified the presence of P carinii in all 17 (100% sensitive, 95% confidence interval [CI] 81-100%) and found no organisms in 50 of 54 microbiologically negative samples (93% specific, 95% CI 82-98%). PCR with a single primer pair was 71% sensitive (44-90%) and 94% specific (85-99%). The sensitivity of conventional staining methods (direct and indirect fluorescence antibody and toluidine-blue-O tests) was significantly less (38-53%) than that of nested PCR (p less than 0.05). In BAL, neither PCR method was significantly better than the conventional staining methods. P carinii was detected in BAL or sputum from 10 immunocompromised patients without microbiological evidence of P carinii pneumonia, which suggests that symptom-free carriers or subclinical infection can exist. P carinii was detected by nested PCR in blood from 2 of 3 patients with disseminated pneumocystosis but in only 1 of 11 patients with P carinii infection restricted to the lungs. Nested PCR on induced sputum is more sensitive than conventional staining methods for the diagnosis of P carinii pneumonia and provides a non-invasive method of detecting disseminated disease.

Animals↗
PubMed1992

Human neutrophil-derived histamine-releasing activity (HRA-N) causes the release of serotonin but not arachidonic acid metabolites from rat basophilic leukemia cells.

The effects of neutrophil-derived histamine-releasing activity (HRA-N) on arachidonic acid (AA) metabolism is unknown. Human basophils exposed to HRA-N released 25% of total histamine but no leukotriene C4 (LTC4). To confirm this phenomenon, rat basophilic leukemia (RBL) cells were exposed to HRA-N as well as anti-IgE, or calcium ionophore A23187. RBL cells incubated with A23187 released 44% of available serotonin and 59 and 124 pmol/10(6) cells of prostaglandin D2 (PGD2) and LTC4, respectively. Anti-IgE stimulation resulted in 34% serotonin release and the generation of 34 pmol PGD2 per 10(6) cells and 72 pmol LTC4 per 10(6) cells. In contrast, HRA-N (2 U/ml) induced 20% serotonin release, 4 pmol PGD2 per 10(6) cells, and 0.6 pmol LTC4 per 10(6) cells. Neither increasing the dose nor the incubation time of HRA-N enhanced the generation of AA metabolite. Additionally, the spectrum of AA metabolites generated by RBL cells in response to those agents was examined by reverse-phase high-performance liquid chromatography. RBL cells stimulated with A23187 released PGD2, LTB4, and its isomers, LTC4, and 5-hydroxyeicosatetraenoic acid. In contrast, HRA-N stimulation resulted in only minimal PGD2 generation and no other discernable AA metabolites. Thus, HRA-N causes selective release of serotonin without inducing AA metabolites. These data suggest that HRA-N activates mast cells through a unique pathway.

Animals↗
PubMed1992

Comparison of human nasal mucosal secretion in vivo and in vitro.

The secretion of proteins from the human nasal mucosa induced by histamine, alpha-adrenergic, beta-adrenergic, and cholinergic agonists was studied in vivo and in vitro. Glandular secretion of lactoferrin, lysozyme (in vivo only), and respiratory glycoconjugates (RGCs) was measured. Vascular permeability was determined in vivo by albumin secretion in relationship to the other proteins. Muscarinic stimulation by methacholine induced significant glandular secretion (lactoferrin, lysozyme and/or RCGs) both in vivo and in vitro, confirming that muscarinic receptors are stimulated directly. Histamine induced predominantly vascular permeability in vivo but caused some glandular secretion as well. However, in vitro, histamine had no effect on glandular secretion, suggesting that histamine acts predominantly on the nasal vascular bed and only affects glandular secretion through reflex actions. Phenylephrine, an alpha-adrenergic agonist, selectively stimulated lysozyme release in vivo, and both RGCs and lactoferrin release in vitro. Thus, alpha-adrenergic stimulation has some direct, albeit minimal, capacity to stimulate mucosal glands. beta-Adrenergic agonists had no effect on glandular secretion or vascular permeability either in vivo or in vitro. Therefore, glandular secretion is directly stimulated by alpha-adrenergic and cholinergic agonists, but not by beta-adrenergic agonists. The stimulation of glandular secretion by histamine is indirect and mediated through the action of neural reflexes.

Adult↗
PubMed1992

The effects of neuropeptides on mucous glycoprotein secretion from human nasal mucosa in vitro.

The role of neuropeptides in the regulation of macromolecule secretion from human nasal mucosa is incompletely understood. Previous in vitro explant culture studies have demonstrated the effects of neuropeptides on lactoferrin release from serous cells and 3H-glucosamine labeled respiratory glycoconjugate secretion from mucus-containing cells. The generation of a new monoclonal antibody, 7F10, has led to the development of an ELISA for high molecular weight respiratory mucous glycoproteins (MGP). This ELISA was used to measure the ability of sensory, parasympathetic and sympathetic neuropeptides to stimulate MGP release from human nasal mucosal fragments in short term explant culture in vitro. Significant MGP release was stimulated by the sensory neuropeptides gastrin releasing peptide (10 microM GRP: 10.6% +/- 2.4% increase, n = 8, P less than 0.01 vs. control), substance P (1 microM SP: 12.5% +/- 5.4%, n = 11, P less than 0.05), neurokinin A (1 microM NKA: 17.8 +/- 4.3%, n = 6, P less than 0.01), while calcitonin gene related peptide (CGRP) was without effect. Vasoactive intestinal peptide (VIP), a neurotransmitter from parasympathetic nerves, induced significant dose dependent MGP secretion, but had no additive or inhibitory interaction with methacholine-induced secretion. Neuropeptide Y (NPY), present in sympathetic nerves, had no effect on MGP secretion. These observations correlate with the effects of neuropeptides on serous cell lactoferrin secretion, and the presence of specific GRP, SP, and VIP binding sites on human nasal submucosal glands that have been detected by autoradiography. GRP and tachykinins (SP and NKA) from sensory nerves, and VIP released during parasympathetic reflexes may significantly stimulate mucous and serous cell secretion from human nasal mucosa in vivo.

Calcitonin Gene-Related Peptide↗
PubMed1992

Gastrin releasing peptide (GRP) binding sites in human bronchi.

The autoradiographic binding site of gastrin releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, were examined in human bronchial mucosa. 125I-GRP bound specifically to submucosal glands and the epithelium. There was limited binding to vessels and bronchial smooth muscle. These observations suggest that GRP or GRP immunoreactive peptides which are present in nerve fibres and pulmonary neuroendocrine cells, may act upon glandular GRP receptors to induce mucus secretion, but that GRP would probably have little effect on vascular permeability or tracheobronchial smooth muscle tone.

Binding Sites↗
PubMed1992

Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia.

Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response was higher (mean optical density ratio: 0.6 vs. 0.23 and 0.2, respectively; P less than .01). Changes in antibody response were investigated in 78 patients for whom serial serum samples taken around the time of bronchoscopy were available. Of the 47 patients with verified PCP, 20 (43%) mounted an antibody response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody response to P. carinii.

Antibodies, Fungal↗
PubMed1992

Bombesin stimulates human nasal mucous and serous cell secretion in vivo.

Bombesin, gastrin-related peptide (GRP), and related peptides sharing the common carboxyterminal sequence stimulate lactoferrin (serous cell marker) and glycoconjugate (mucous cell and goblet cell marker) release from human nasal mucosal explants in vitro. In vivo, GRP released from trigeminal sensory nerves may act upon GRP-bombesin binding sites on respiratory epithelial cells and submucosal glands. To determine whether GRP-bombesin can stimulate nasal secretion in vivo, bombesin was administered to eight normal subjects by unilateral, topical administration. Secretions from both nostrils were collected for measurement of total protein, lysozyme, hexose-containing glycoconjugates, and albumin (marker of vascular permeability). Baseline secretions contained 72.0 +/- 17.3 micrograms/ml of total protein, 14 +/- 2 micrograms/ml of lysozyme, 113 +/- 44 micrograms/ml of hexose-containing glycoconjugates, and 7.8 +/- 3.4 micrograms/ml of albumin. Hexose-containing glycoconjugate secretion was significantly increased after 1 nmol (385 +/- 63 micrograms/ml, P less than 0.001 by analysis of variance), 10, 100, and 1,000 nmol of bombesin, but the secretion was not dose dependent. Significant lysozyme (24 +/- 3 micrograms/ml, P less than 0.05) and total protein (155 +/- 23 micrograms/ml, P less than 0.01) secretion occurred after 1,000 nmol. No statistically significant changes in albumin secretion occurred at any dose. Saline had no significant effects on secretion. Therefore, bombesin stimulated secretion from submucosal glands and possibly epithelial cells in the human nose without affecting vascular permeability.

Adult↗
PubMed1992

Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study.

Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation.

Acquired Immunodeficiency Syndrome↗