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Biomedical subjects

J Lohmeyer

Publications and source records attributed to J Lohmeyer.

At least 19 recordsLinked to original sources
PubMed2007

[Bridging peripheral nerve defects by means of nerve conduits].

BACKGROUND: The nerve autograft is the gold standard for the reconstruction of peripheral nerve defects. In short gaps, nerve repair by means of tubulization has become an alternative. This technique is discussed based on the current literature and our own experience. PATIENTS AND METHODS: Nerve reconstruction by means of tubulization was performed in 11 patients. Nerve gaps in the hand of up to 18 mm were reconstructed. Sensibility was assessed using static and dynamic two point discrimination (s-, d2PD) and monofilament testing 3, 6 and 12 months postoperatively. RESULTS: Three out of 11 patients complained of a temporary foreign body sensation in the area of the implant; this was persistent in one case. Four out of six patients showed excellent results with s2PD of 15 mm, S0), another poor sensibility (s2PD 15 mm, S3). D2PD and monofilament testing confirmed these results. CONCLUSIONS: Nerve reconstruction by means of tubulization seems to be a suitable method for certain indications in the reconstruction of short defects of digital and palmar nerves. Donor site morbidity can be avoided. Similarly to nerve transplantation, the operation requires microsurgical skills.

Absorbable Implants↗
PubMed2005

Systemic aspergillosis with predominant genitourinary manifestations in an immunocompetent man: what we can learn from a disastrous follow-up.

Prostatic aspergillosis is a rare finding with only ten cases reported previously. We report the first case of systemic aspergillosis predominantly presenting with prostatic involvement and, clinically, with urinary retention in an immunocompetent host. Routine transurethral resection was performed due to benign prostatic hyperplasia with subvesical obstruction. Concomitant prostatic aspergillosis was diagnosed without signs of systemic infection. In the clinical follow-up systemic aspergillosis became rapidly progressive requiring complex surgical interventions and long-term antifungal therapy. The current literature is reviewed, and diagnostic and management options are discussed.

Abscess↗
PubMed2004

Pro- and antifibrinolytic properties of human pulmonary microvascular versus artery endothelial cells: impact of endotoxin and tumor necrosis factor-alpha.

OBJECTIVE: Microvascular thrombosis is a common feature of acute inflammatory lung injury, as occurs in sepsis and acute respiratory distress syndrome, but the underlying pathomechanisms are presently not fully understood. DESIGN: Experimental. SETTING: University laboratory. SUBJECTS: Lung endothelial cells. INTERVENTIONS: We characterized the expression of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) as well as plasminogen activator inhibitor (PAI)-1 and PAI-2 in human endothelial cells (EC) from the microvascular pulmonary circulation (HMVEC-L) and compared it with that of EC from pulmonary artery (HPAEC) and umbilical vein (HUVEC) under baseline conditions and upon stimulation with either tumor necrosis factor-alpha or lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were employed for quantification of messenger RNA and protein concentrations. Under baseline conditions, comparable PAI-1 expression was noted in all EC. HPAEC were characterized by significantly higher baseline expression of t-PA and PAI-2 compared with HUVEC and HMVEC-L. In contrast, u-PA messenger RNA concentrations were found to be significantly higher in nonstimulated HMVEC-L compared with HUVEC and HPAEC. In all EC, stimulation with tumor necrosis factor-alpha and lipopolysaccharide increased the expression of PAI-1, PAI-2, and u-PA and decreased t-PA expression. The changes in messenger RNA content were reflected by corresponding changes in the protein concentrations. CONCLUSIONS: High baseline u-PA expression is a prominent feature of human lung microvascular EC, whereas pulmonary artery EC are characterized by high t-PA concentrations. Microbial and inflammatory challenge provokes up-regulation of PAI-1 and PAI-2 and down-regulation of t-PA in both macro- and microvascular pulmonary EC, which may favor local fibrin deposition.

Base Sequence↗
PubMed2004

Inhaled iloprost is a potent acute pulmonary vasodilator in HIV-related severe pulmonary hypertension.

As antiretroviral therapy has improved life expectancy in human immunodeficiency virus (HIV) infection, the life-limiting complication of HIV-related pulmonary hypertension has come into focus. Inhalation of the stable prostacyclin analogue iloprost is an effective treatment for various forms of precapillary pulmonary hypertension. The main objective of the present study was to evaluate the safety and efficacy of inhaled iloprost in HIV-related pulmonary hypertension. In eight patients with severe pulmonary hypertension related to HIV infection, right heart and femoral artery catheterisation were performed. The acute effect of oxygen, inhaled nitric oxide and aerosolised iloprost was investigated. Four patients underwent long-term treatment with inhaled iloprost. The rank order of pulmonary vasodilatory potency was iloprost>NO>O2, with a maximum reduction (mean +/- SEM) in pulmonary vascular resistance of 30.6 +/- 3.1% (p < 0.001), 5.9 +/- 3.9% and -0.6 +/- 3.9%, respectively. Concomitantly, inhaled iloprost significantly increased the cardiac index and central venous oxygen saturation. Chronic treatment with inhaled iloprost tended to improve the 6 min walking distance and decreased pulmonary vascular resistance in all patients (although not significantly). No serious adverse events and no major interactions with the ongoing antiretroviral therapy were noted. In conclusion, inhaled iloprost is a potent pulmonary vasodilator in human immune deficiency virus-related pulmonary hypertension. Future studies are warranted to confirm the encouraging long-term beneficial results observed in the present limited number of patients.

Administration, Inhalation↗
PubMed2003

Longitudinal evaluation of serum estradiol and estrone in male patients infected with the human immunodeficiency virus.

In patients with human immunodeficiency virus (HIV) infection alteration of various endocrine functions have been described. However, there is limited information available on estrogens and their function in these patients. The aim of this study was to evaluate the pituitary and testicular endocrine markers: 14 HIV-positive men were included into the longitudinal study with a follow up to of 18 month period. None of the patients had a history or clinical evidence of endocrine dysfunction. Follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estrone, estradiol, and testosterone were measured in serum by commercially available radioimmunoassays. Prolactin levels were not affected in the patients. LH and FSH remained within normal range, but at the end of the study period we observed a significant increase of LH (p < 0.05). In addition, testosterone levels were normal with a slight reduction at the end of the 18-month observation period (p <0.05). Both estrone and estradiol were significantly increased with a further rise at the end of the study (p <0.05). In summary, the elevation of the serum estrone and estradiol in HIV-afflicted patients correlated with the progress of the HIV-disease, being paralleled by a decrease in testosterone. The altered relation of estrogens and testosterone may in a part be responsible for the complaints of decreased libido and increased impotence often observed in HIV-infected men.

Adult↗
PubMed2003

Osteopenia in HIV-infected women prior to highly active antiretroviral therapy.

BACKGROUND AND OBJECTIVES: Multiple endocrine and metabolic consequences of human immunodeficiency (HIV) infection exist that alter bone metabolism in patients with acquired immune deficiency syndrome (AIDS). Osteopenia in AIDS patients has been associated with antiretroviral therapy particularly with protease inhibitors. However, there is very little data on bone metabolism in female subjects with AIDS prior to highly active antiretroviral therapy. METHODS: Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA) in 50 HIV-infected female outpatients (mean age 37 years) both in the lumbar spine and the Ward's triangle of the left hip. Additional parameter assessed were demographics, smoking, CD4 counts, fasting metabolic parameters and biochemical markers of bone metabolism. None of the patients received reverse transcriptase inhibitors or protease inhibitors, vitamin D or calcium-supplementation. RESULTS: The serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D (1,25(OH2)D) were significantly reduced compared to 50 age-matched female healthy controls. Urinary calcium and pyridinium crosslinks-excretion corrected for creatinine excretion were elevated (P<0.01) and were likewise significantly correlated with the loss of CD4 cells (P<0.05). Serum osteocalcin was significantly lowered (P<0.01). Reduced BMD of the lumbar spine (t -score <-2.5 SD below normal) was found in seven patients (14%) and osteopenia (t -score -1.0 to -2.5 SD below normal) was diagnosed in 31 (62%). No patient had a fracture since being infected with HIV. The BMD was reduced both in lumbar spine and the hip measured in the left Ward's triangle. There were significant positive correlation between the CD4 counts and 1,25(OH2)D (P<0.05). Neither the CD4 counts nor the duration of disease correlated with BMD. The reduced bone formation rate was linked to progressive loss of CD4-cell count. CONCLUSION: Osteopenia in HIV-infected female subjects is commonly manifested both in lumbar spine and Ward's triangle of the hip. There is a dissociation between lowered markers of bone formation rate and the increased bone resorption expressed as elevated urinary crosslinks and calcium excretion. Furthermore, the decreased levels of 1,25(OH2)D may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest that further research is necessary to determine, whether low levels of 1,25(OH2)D lead to an accelerated inflammatory process in AIDS, since 1,25(OH)2D is known as an endogenous immune modulator suppressing formation of activated T cells and cell proliferation.

Absorptiometry, Photon↗
PubMed2002

Role of endothelial MCP-1 in monocyte adhesion to inflamed human endothelium under physiological flow.

Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine involved in monocyte traffic across endo- and epithelial barriers both in vitro and in vivo. However, the contribution of endothelial MCP-1 signaling via its CCR2 receptor in monocyte adhesion to inflamed endothelium under flow is incompletely understood. A sensitive flow chamber assay was used to assess monocyte adhesion to TNF-alpha-activated primary human pulmonary artery endothelial cells (HPAEC) during physiological shear stress. Monocyte adhesion was markedly reduced ( approximately 45%) when HPAEC-derived MCP-1 was either neutralized with anti-MCP-1 mAb or inhibited by translational arrest of MCP-1 mRNA transcripts with MCP-1 antisense oligomers. Corresponding efficacy was observed for blockade of monocyte CCR2 receptor function by anti-CCR2 mAb or MCP-1 antagonists (9-76 analog). The impact of endothelial MCP-1 on monocyte-HPAEC adhesion occurred via beta(2)-integrin but not via beta(1)-integrin adhesion pathways. In this line, pretreatment of monocytes with MCP-1 but not RANTES provoked a rapid and transient neoepitope 24 expression on beta(2)-integrin alpha-chains, as analyzed by increased reporter mAb24 binding. Collectively, our data show an important cross talk of endothelial MCP-1 with monocyte CCR2 effecting monocyte firm adhesion to inflamed HPAEC under physiological flow conditions.

Antibodies, Monoclonal↗
PubMed2001

Alveolar JE/MCP-1 and endotoxin synergize to provoke lung cytokine upregulation, sequential neutrophil and monocyte influx, and vascular leakage in mice.

The C-C chemokine monocyte chemotactic protein 1 (JE/MCP-1) is a key cytokine for lung monocyte recruitment, and may be detected in high levels in the alveolar space in lung injury. We hypothesized that alveolar JE/MCP-1 might synergize with endotoxin in this compartment to elicit lung inflammatory events. Intratracheal instillation of JE/MCP-1 into BALB/c mice did not provoke increased bronchoalveolar lavage tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and macrophage inflammatory protein 2 (MIP-2) levels, but elicited monocyte recruitment into this compartment. Intratracheal Escherichia coli endotoxin provoked elevated lavage TNF-alpha, IL-6, and MIP-2 levels, peaking after 6 h in parallel with increased alveolar neutrophil numbers, in the absence of vascular leakage. Mice receiving both endotoxin and JE/ MCP-1 showed drastically increased lavage TNF-alpha, IL-6, and MIP-2 levels, 22-fold higher lavage neutrophil numbers, and lung vascular leakage. Moreover, an 8-fold increased alveolar accumulation of monocytes, peaking at 48 h together with expansion of the resident alveolar macrophage pool, was noted. Intraperitoneal instead of alveolar deposition of MCP-1 or endotoxin failed to reproduce the synergistic response, and the same was true for employment of RANTES instead of MCP-1. Blockade of neutrophil recruitment by anti-CD18 did not affect the intra-alveolar cytokine response to MCP-1 plus endotoxin. Together, JE/MCP-1 and endotoxin, when coappearing in the alveolar compartment at low dosage, elicit an early phase of lung inflammatory injury with increased cytokine synthesis and neutrophil recruitment, and a late phase of enhanced monocyte traffic and expansion of the alveolar macrophage pool.

Animals↗
PubMed2001

Impact of a phosphorothioate oligodeoxynucleotide MCP-1 on NF-kappaB, AP-1, SP1 and NF-kappaB, and AP-1 subunit composition in human pulmonary endothelial cells.

Phosphorothioate oligodeoxynucleotides (PS-ODN) are widely used prototypic antisense oligomers for sequence-specific suppression of normal and diseased gene expression. As polyanionic molecules, however, PS-ODN may also evoke nonsequence-specific side effects. The objective of the present study was to evaluate the impact of PS-ODN treatment of human pulmonary artery endothelial cells (HPAEC) and microvascular endothelial cells of the lung (HMVEC-L) on the cellular pool of the transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) as well as Sp1, using gel shift assays. In addition, by performing supershift assays, we investigated whether antisense treatment of endothelial cells affected the subunit composition of NF-kappaB and AP-1. Our data show that pretreatment of HPAEC and HMVEC-L with PS-ODN doses ranging from 50 to 5000 nM did not affect the total NF-kappaB, AP-1, or Sp1 pool in tumor necrosis factor-alpha (TNF-alpha)-activated endothelial cells (EC) or the subunit composition of the transcription factors NF-kappaB and AP-1. These findings suggest that putative nonsequence-specific effects of PS-ODN are not due to interactions of these oligomers with the transcription factors NF-kappaB, AP-1, or Sp1, at least in the EC type, a common target in transfection studies.

Base Sequence↗
PubMed2001

Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14.

The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident alveolar macrophages (rAMs). Using the intravenous injected fluorescent dye PKH26, which accumulated in rAMs without labeling blood leukocytes, we developed a technique that permits the identification, isolation, and functional analysis of monocytes recruited into lung alveoli of mice. Alveolar deposition of murine JE, the homologue of human monocyte chemoattractant protein (MCP)-1 (JE/MCP-1), in mice provoked an alveolar influx of monocytes that were recovered by bronchoalveolar lavage and separated from PKH26-stained rAMs by flow cytometry. Alveolar recruited monocytes showed a blood monocytic phenotype as assessed by cell surface expression of F4/80, CD11a, CD11b, CD18, CD49d, and CD62L. In contrast, CD14 was markedly upregulated on alveolar recruited monocytes together with increased tumor necrosis factor-alpha message, discriminating this monocyte population from peripheral blood monocytes and rAMs. Thus monocytes recruited into the alveolar air space of mice in response to JE/MCP-1 keep phenotypic features of blood monocytes but upregulate CD14 and are "primed" for enhanced responsiveness to endotoxin with increased cytokine expression.

Animals↗
PubMed2000

Monocyte migration through the alveolar epithelial barrier: adhesion molecule mechanisms and impact of chemokines.

Alveolar monocyte influx requires adherence and transmigration through the vascular endothelium, extracellular matrix, and alveolar epithelium. For investigating the monocyte migratory process across the epithelial barrier, we employed both the A549 cell line and isolated human alveolar epithelial cells. Under baseline conditions, spontaneous bidirectional transepithelial monocyte migration was noted, which was dose-dependently increased in the presence of the monocyte chemoattractant protein-1. TNF-alpha stimulation of the alveolar epithelium provoked the polarized apical secretion of monocyte chemoattractant protein-1 and RANTES and up-regulation of ICAM-1 and VCAM-1 expression, accompanied by markedly enhanced transepithelial monocyte traffic in the basal-to-apical direction. Multiple adhesive interactions were noted to contribute to the enhanced monocyte traffic across the TNF-alpha-stimulated alveolar epithelium: these included the beta 2 integrins CD11a, CD11b, CD11c/CD18, the beta 1 integrins very late Ag (VLA)-4, -5, and -6, and the integrin-associated protein CD47 on monocytes, as well as ICAM-1, VCAM-1, CD47, and matrix components on the epithelial side. In contrast, spontaneous monocyte migration through unstimulated epithelium depended predominantly on CD11b/CD18 and CD47, with some additional contribution of VLA-4, -5, and -6. In summary, unlike transendothelial monocyte traffic, for which beta 1 and beta 2 integrins are alternative mechanisms, monocyte migration across the alveolar epithelium largely depends on CD11b/CD18 and CD47 but required the additional engagement of the beta 1 integrins for optimal migration. In response to inflammatory challenge, the alveolar epithelium orchestrates enhanced monocyte traffic to the apical side by polarized chemokine secretion and up-regulation of ICAM-1 and VCAM-1.

Cell Adhesion Molecules↗
PubMed2000

Changes in calciotropic hormones and biochemical markers of bone metabolism in patients with human immunodeficiency virus infection.

Data on the bone metabolism of human immunodeficiency virus (HIV)-infected patients are still extremely rare. To investigate the influence of HIV infection on the calciotropic hormones and markers of bone metabolism, we therefore performed a cross-sectional study on 100 patients (65 males and 35 females) with proven HIV infection. The following criteria were used for exclusion from the study: age less than 20/more than 50 years, confinement to bed, wasting symptoms, treatment with agents containing ketoconazole, renal or hepatic insufficiency, clinical or echographic signs of liver cirrhosis, endocrine diseases, or treatment with medications known to influence bone metabolism. Bone mineral content (BMC) was determined by single-photon absorptiometry on the left forearm. Reduced BMC was found among the male and female HIV-infected patients. Additional long-term use of heroin resulted in a severe loss of mineralization in the respective females. The markers of bone metabolism were determined in urine and serum samples. Significantly lower osteocalcin concentrations were found, indicating a reduced bone formation rate whose severity showed a significant correlation with the progressive loss of CD4 helper cells and was independent of low vitamin D3 levels (1,25-dihydroxycholecalciferol) and alterations of protein metabolism. Increased urinary excretion of cross-links as an expression of enhanced bone resorption was likewise significantly correlated with the loss of CD4 helper cells and independent of the vitamin D concentration and protein metabolism. It is therefore concluded that the changes in bone metabolism are mainly due to mechanisms of the impaired immune defense of HIV-infected patients.

Adult↗
PubMed2000

Antisense oligomers for selective suppression of MCP-1 synthesis in human pulmonary endothelial cells.

Endothelial synthesis of the C-C chemokine monocyte chemotactic protein-1 (MCP-1) has been implicated in the regulation of monocyte recruitment for extravascular pools under both physiologic and inflammatory conditions. We designed and characterized five antisense phosphorothioate oligodeoxynucleotides (PS-ODN) targeting MCP-1 secretion by human pulmonary artery endothelial cells (HPAEC) and pulmonary microvascular endothelial cells (HMVEC-L). The most effective PS-ODN (MCP-1 AS 2) dose-dependently suppressed the secretion of MCP-1 but not the secretion of the C-X-C chemokine interleukin-8 (IL-8) in both HPAEC and HMVEC-L in the nanomolar concentration range. Mismatch controls bearing 2 or 4 bp substitutions showed markedly reduced inhibitory capacity. MCP-1 mRNA levels were not affected even at the highest PS-ODN doses employed (ribonuclease protection assay), suggesting a translational arrest of MCP-1 production. Accordingly, PS-ODN exhibited no nonspecific side effects on immediate-early gene regulation of the transcription factor nuclear factor-kappaB (NF-kappaB), as analyzed by gel shift assays. Antisense pretreatment of HPAEC reduced the monocyte chemotactic bioactivity liberated from tumor necrosis factor-alpha (TNF-alpha)-activated endothelial cells (EC) and reduced the TNF-alpha-induced transendothelial monocyte migration. We conclude that nanomolar concentrations of specific antisense oligodeoxynucleotides effectively inhibit human endothelial MCP-1 synthesis and may thus provide a rational approach to modulate monocyte recruitment under inflammatory conditions.

Cell Line↗
PubMed2000

Phenotypic characterization of alveolar monocyte recruitment in acute respiratory distress syndrome.

In 49 acute respiratory distress syndrome (ARDS) patients, the phenotype of alveolar macrophages (AMs) was analyzed by flow cytometry. Bronchoalveolar lavage (BAL) was performed within 24 h after intubation and on days 3-5, 9-12, and 18-21 of mechanical ventilation. The 27E10(high)/CD11b(high)/CD71(low)/ 25F9(low)/HLA DR(low)/RM3/1(low) AM population in the first BAL indicated extensive monocyte influx into the alveolar compartment. There was no evidence of increased local AM proliferation as assessed by nuclear Ki67 staining. Sequential BAL revealed two distinct patient groups. In one, a decrease in 27E10 and CD11b and an increase in CD71, 25F9, HLA DR, and RM3/1 suggested a reduction in monocyte influx and maturation of recruited cells into AMs, whereas the second group displayed sustained monocyte recruitment. In the first BAL from all patients, monocyte chemoattractant protein (MCP)-1 was increased, and AMs displayed elevated MCP-1 gene expression. In sequential BALs, a decrease in MCP-1 coincided with the disappearance of monocyte-like AMs, whereas persistent upregulation of MCP-1 paralleled ongoing monocyte influx. A highly significant correlation between BAL fluid MCP-1 concentration, the predominance of monocyte-like AMs, and the severity of respiratory failure was noted.

Adult↗
PubMed1999

Surfactant protein A down-regulates proinflammatory cytokine production evoked by Candida albicans in human alveolar macrophages and monocytes.

Surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammatory events. We analyzed the impact of SP-A on the Candida albicans-induced cytokine response in human alveolar macrophages (AM) and its precursor cells, the monocytes, which rapidly expand the alveolar mononuclear phagocyte pool under inflammatory conditions. Both recombinant human SP-A and natural canine SP-A were employed. SP-A dose-dependently down-regulated the proinflammatory cytokine response of AM and monocytes to both viable and nonviable Candida, including TNF-alpha, IL-1beta, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1. In contrast, SP-A did not affect the baseline liberation of these cytokines. The release of the antiinflammatory cytokines IL-1 receptor antagonist and IL-6 was not inhibited by SP-A under baseline conditions and in response to fungal challenge. The inhibitory effect of SP-A on proinflammatory cytokine release was retained upon reassembly of the apoprotein with natural surfactant lipids and in the presence of serum constituents, for mimicry of plasma leakage into the alveolar space. It was not reproduced by the homologous proteins complement component C1q and type IV collagen. It was independent of Candida-SP-A binding and phagocyte C1q receptor occupancy, but apparently demanded SP-A internalization by the mononuclear phagocytes, effecting down-regulation of proinflammatory cytokine synthesis at the transcriptional level. We conclude that SP-A limits excessive proinflammatory cytokine release in AM and monocytes confronted with fungal challenge in the alveolar compartment. These data lend further credit to an important physiological role of SP-A in regulating alveolar host defense and inflammation.

Blood Proteins↗
PubMed1999

Expression of mucosa-related integrin alphaEbeta7 on alveolar T cells in interstitial lung diseases.

The expression of alphaEbeta7 integrin has been related to the selective retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. To identify potential disease-associated alphaEbeta7 expression patterns on cells accounting for lymphocytic alveolitis in interstitial lung disease (ILD), alphaE expression on CD4+ and CD8+ T cell subsets was evaluated by dual-colour flow cytometry in peripheral blood and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF; n = 18), hypersensitivity pneumonitis (HP; n = 20) and sarcoidosis (n = 44) in comparison with healthy controls (n = 15). In both healthy individuals and all patient groups the proportion of alphaE-bearing T cells in peripheral blood was < 2%, whereas the vast majority of alveolar CD8+ T cells consistently co-expressed alphaE. Absolute alveolar CD8+alphaE+ cell numbers/ml were up to 30-fold increased in HP patients. Proportions of alphaE-bearing CD4+ cells in BALF were significantly elevated in IPF (74.0 +/- 2.7%) and HP (70.0 +/- 2.4%) compared with normals (30.0 +/- 1.8%) (mean +/- s.e.m.; P < 0.01). In sarcoidosis, the alphaE expression on BALF CD4+ cells displayed subgroup dependency: proportions significantly lower than normal were noted in chest radiographic stage I (14.3 +/- 1.5%), but increased proportions in stages II (50.0 +/- 3.8%) and III (64.0 +/- 4.8%). Correlations between common markers of T cell activation or BALF transforming growth factor-beta (TGF-beta ) bioactivity and alphaE expression were not noted. We conclude that the vast majority of alveolar CD8+ T cells consistently express alphaEbeta7 and that distinct patterns of alphaEbeta7 expression on alveolar CD4+ lymphocytes in sarcoidosis are related to the diverse manifestations of the sarcoid inflammatory process in the lung.

Adolescent↗
PubMed1999

Cationic lipids employed for antisense oligodeoxynucleotide transport may inhibit vascular cell adhesion molecule-1 expression in human endothelial cells: a word of caution.

Antisense oligodeoxynucleotides (ODN) have become a powerful tool to achieve specific gene inhibition in various cell types, including endothelial cells. The low spontaneous cellular uptake of ODN, however, usually requires the employment of transmembrane carriers, such as the positively charged liposome formulation dioleyloxypropyltrimethyl ammonium chloride/dioleoylphosphatidylethanolamine (DOTMA/DOPE). In the present study, we observed that DOTMA/DOPE per se interferes with the inducible expression of vascular cell adhesion molecule-1 (VCAM-1) in human pulmonary artery endothelial cells (HPAEC). By RT-PCR analysis, a dose-dependent suppression of VCAM-1 but not intracellular adhesion molecule-1 (ICAM-1) mRNA levels in tumor necrosis factor-alpha (TNF-alpha)-challenged HPAEC pretreated with DOTMA/DOPE (5-20 microg/ml) was demonstrated. Correspondingly, a strong reduction of TNF-alpha-induced VCAM-1 but not ICAM-1 cell surface expression on HPAEC was observed. These DOTMA/DOPE-induced changes were not due to alterations in VCAM-1 mRNA stability, nor did DOTMA/DOPE inhibit TNF-alpha-induced NF-kappaB-like binding activity in nuclear extracts of HPAEC, as analyzed by electrophoretic mobility shift assay. In contrast, DOTMA/DOPE effected a dose-dependent increase in AP-1-like binding activity in nuclear extracts of HPAEC, as analyzed by Western blotting and EMSA. We conclude that positively charged liposome preparations may per se inhibit TNF-alpha-induced endothelial VCAM-1 expression, and this may be related to changes in AP-1 but not NF-kappaB-dependent transcriptional control. Notably, when used at concentrations below 5 microg/ml, DOTMA/DOPE may be employed for specific antisense-mediated downregulation of VCAM-1 in the absence of vehicle-related side effects on adhesion molecule transcription.

Blotting, Western↗