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Biomedical subjects

A Bastian

Publications and source records attributed to A Bastian.

At least 19 recordsLinked to original sources
PubMed2006

Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma.

BACKGROUND: In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been demonstrated at increased levels in sera of patients with LS in parallel with disease activity. Human beta-defensins (hBDs) are peptides with antimicrobial activity, but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T-cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well-known effects on collagen metabolism. OBJECTIVES: We sought to investigate the effects of UVA1 on the expression and modulation of hBDs and several pro-inflammatory cytokines in LS. METHODS: UVA1 phototherapy was performed five times weekly for 8 weeks resulting in a total of 40 treatment sessions (single dose 20 J cm2, cumulative dose 800 J cm2). hBD-1, hBD-2 and hBD-3 mRNA as well as tumour necrosis factor-alpha, transforming growth factor-beta, interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by quantitative real-time reverse transcription-polymerase chain reaction in lesional and unaffected skin of patients with LS. RESULTS: Skin status markedly improved in all 14 patients, resulting in a significant reduction of the clinical score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels were higher in lesional skin compared with unaffected skin and skin from healthy volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6 and IL-8 mRNA levels were significantly elevated in lesional skin and significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3, IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1 phototherapy. CONCLUSIONS: hBDs and IL-6 and IL-8, cytokines with pivotal importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional skin of patients with LS. Their pathogenetic relevance with respect to clinical improvement needs further investigation.

Adult↗
PubMed2005

Sildenafil improves hemodynamic parameters in COPD--an investigation of six patients.

Pulmonary hypertension (PH) is an important predictor of mortality in chronic obstructive pulmonary disease (COPD). The phosphodiesterase 5 inhibitor sildenafil has been demonstrated to reduce pulmonary arterial pressure (PAP) in different diseases. We wanted to investigate the effect of sildenafil on hemodynamic parameters and the 6-min walk test (6 MWT) in six patients with severe COPD and echocardiographically estimated PH. A 6 MWT was performed and hemodynamic parameters were measured by right heart catheterization before and 1 and 12h after injection of 50mg sildenafil intravenously. A 3-months period of peroral sildenafil therapy 50mg twice daily followed and finally hemodynamic parameters and a 6 MWT were repeated. Intravenously applied sildenafil could be demonstrated to reduce PAP and pulmonary vasculature resistance (PVR) significantly. And after 3 months of oral sildenafil, the mean PAP has decreased from 30.2+/-5.5 mmHg (range: 24-39 mmHg) to 24.6+/-4.2 mmHg (range: 20-30 mmHg) (p=0.01). The PVR has decreased from 401+/-108 dyn s cm(-5) (range: 266-558 dyn s cm(-5)) to 264+/-52 dyn s cm(-5) (range: 204-333 dyn s cm(-5)) (p<0.05). Physical conditions improved: the 6-min walk distance increased from 351+/-49 to 433+/-52 m. In conclusion, in six patients suffering from severe COPD we could demonstrate significantly improved hemodynamic parameters after 50 mg sildenafil intravenous application. And after 3 months of oral sildenafil, walking distance in the 6 MWT increased significantly as well as hemodynamic parameters in the five patients who had accepted a second right heart catheterization.

Administration, Oral↗
PubMed2005

Spectroscopic evidence of cerebral axonopathy in patients with "pure" adrenomyeloneuropathy.

BACKGROUND: Adrenomyeloneuropathy (AMN) is the adult variant of X-linked adrenoleukodystrophy. The disease pathology is usually limited to spinal cord and peripheral nerves, and when this is the case, it is referred to as "pure" AMN. Histopathology shows cerebral involvement even in pure AMN; however, not much is known about the nature, extent, and clinical relevance of these findings. OBJECTIVE: To investigate brain involvement in AMN patients with normal MRI, employing multislice MR spectroscopic imaging. METHODS: Twelve men with pure AMN were compared with 19 age-matched healthy volunteers. Metabolite ratios (N-acetylaspartate [NAA]/choline [Cho], NAA/creatine [Cr], and Cho/Cr) were measured from seven brain regions. Global metabolite ratios were generated as an average of these seven regional ratios. The Expanded Disability Status Scale (EDSS) was used for neurologic evaluation. RESULTS: The patients with AMN showed reduced global NAA/Cho (AMN 1.40 +/- 0.16 vs controls 1.75 +/- 0.34; p = 0.003)) and global NAA/Cr (AMN 2.32 +/- 0.13 vs controls 2.62 +/- 0.43; p = 0.03). Regionally, NAA/Cho was lowered in the internal capsule (AMN 1.30 +/- 0.20 vs controls 1.69 +/- 0.37; p = 0.002) and in parieto-occipital white matter (AMN 1.45 +/- 0.19 vs controls 1.78 +/- 0.55; p = 0.04). NAA/Cr was lowered in parieto-occipital white matter (AMN 2.34 +/- 0.31 vs controls 2.83 +/- 0.71; p = 0.04). EDSS demonstrated an inverse association with global NAA/Cr (r = -0.65, p = 0.02) and NAA/Cr in centrum semiovale (r = -0.73, p = 0.006) and in parieto-occipital white matter (r = -0.64, p = 0.02). Cho/Cr was not significantly elevated. CONCLUSIONS: (1)H-MR spectroscopic imaging is able to detect biochemical abnormalities suggestive of axonal damage even in the brains of patients with pure adrenomyeloneuropathy. The axonopathy is most prominent in internal capsule and parieto-occipital white matter and may contribute to clinical disability.

Adrenoleukodystrophy↗
PubMed2002

The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells.

BACKGROUND: Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. MATERIALS AND METHODS: After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. RESULTS: ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. CONCLUSION: Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Human alpha-defensin 1 (HNP-1) inhibits adenoviral infection in vitro.

Adenoviral gene transfer is a promising tool for direct treatment of cystic fibrosis by local application of the CFTR-gene via the airway. However, various host defense mechanisms reduce the adenoviral infectivity and hereby the success of adenoviral transduction. Twenty-eight of 62 BALs from various patients exerted strong inhibition of adenoviral infection of 293 cells. This soluble activity could be attributed to larger peptides rather than to small molecules. Beside immunoglobulins, certain epithelial cell-derived anti-microbial polypeptides called defensins might be involved. Therefore, we investigated the inhibitory potential of the defensins HNP-1 and HBD-2 on adenoviral infectivity. 293 cells infected with adenovirus-type 5 were treated with both peptides. Compared to control, HNP-1 reduced adenoviral infection by more than 95% if administered at 50 microg/ml, and the IC50-value was 15 microg/ml. In contrast, HBD-2 was much less efficient and did not block adenoviral infection at doses up to 50 microg/ml. Our data demonstrate that the presence of certain polypeptides in the BAL, i.e. the defensin HNP-1, might be the major obstacle for adenoviral gene transfer, particularly in patients with inflammatory diseases.

Adenoviridae↗
PubMed2000

Pericardiocentesis: differential aspects of a common procedure.

OBJECTIVE: To evaluate the risk and effectiveness of pericardiocentesis in primary and repeat cardiac tamponade. DESIGN: Retrospective analysis. SETTING: Intensive care unit in a medical university hospital. PATIENTS: Sixty-three consecutively admitted patients with cardiac tamponade. INTERVENTIONS: In all patients pericardiocentesis was performed via the subxiphoid pathway after echocardiographic detection of the pericardial effusion. MEASUREMENTS AND RESULTS: There was no adverse event in patients undergoing primary pericardiocentesis, which was sufficient to resolve pericardial effusion in 51 of 63 patients (81%). However, repeat pericardiocentesis necessitated by the recurrence of symptomatic pericardial effusion yielded suboptimal results in 10 of 12 patients (83%). CONCLUSION: Pericardiocentesis is the treatment of choice for primary symptomatic pericardial effusion. In recurrent pericardial effusion surgical approaches appear to be preferable.

Adult↗
PubMed2000

Immunoglobulin A and secretory immunoglobulin A in the bronchoalveolar lavage from patients after lung transplantation.

Secretory immunoglobulin A (sIgA) is the most important Ig on mucosal surfaces. In bronchoalveolar lavage (BAL) fluid, sIgA is mainly produced by bronchus-associated lymphoid tissue (BALT). The presence of pre-formed antibodies against donor tissue in kidney transplantation is associated with hyperacute rejection, indicating a humoral (antibody-mediated) reaction. In heart and liver transplantation, humoral rejection has also been documented. The goal of this study was to evaluate the role of IgA in patients after lung transplantation. An enzyme-linked immunosorbent assay was established to determine the levels of sIgA, IgA, and total protein in the lavage. IgA and sIgA were both detectable in BAL from transplanted lungs. IgA and sIgA levels were both higher during episodes of infection than during episodes of rejection or during the control episodes. The level of IgA during episodes of rejection equaled the level of IgA during the control episodes. The level of sIgA was significantly decreased during episodes of acute rejection (1.8 +/- 1.0 microg/mL) when compared with the control (7.2 +/- 1.0 microg/mL; p = 0.013). This study demonstrates that BALT retains the ability to produce Ig even after lung transplantation. The levels of IgA and sIgA and their ratio do not contribute to the differentiation between rejection and infection in lung-transplanted patients.

Acute Disease↗
PubMed2000

Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.

BACKGROUND: Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. OBJECTIVE: Evaluation of methods for the rapid diagnosis of CMV pneumonitis. METHODS: The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. RESULTS: In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. CONCLUSIONS: PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis.

Adolescent↗
PubMed1999

The distribution of neuronal population activation (DPA) as a tool to study interaction and integration in cortical representations.

In many cortical areas, simple stimuli or task conditions activate large populations of neurons. We hypothesize that such populations support processes of interaction within parametric representations and integration of multiple sources of input and we propose to study these processes using distributions of population activation (DPAs) as a tool. Such distributions can be viewed as neuronal representations of continuous stimulus or task parameters. They are built from basis functions contributed by each neuron. These functions may be explicitly chosen based on tuning curves or receptive field profiles. Or they may be determined by minimizing the distance between chosen target distributions and the constructed DPAs. In both cases, construction of the DPA is based on a set of reference conditions in which the stimulus or task parameters are sampled experimentally. In a second step, basis functions are kept fixed, and the DPAs are used to explore time dependent processing, interaction and integration of information. For instance, stimuli which simultaneously specify multiple parameter values can be used to study interactions within the parametric representation. We review an experiment, in which the representation of retinal position is probed in this way, revealing fast excitatory interactions among neurons representing similar retinal positions and slower inhibitory interactions among neurons representing dissimilar retinal positions. Similarly, DPAs can be used to analyze different sources of input that are fused within a parametric representation. We review an experiment in which the representation of the direction of goal-directed arm movements in motor and premotor cortex is studied when prior and current information about upcoming movement tasks are integrated.

Animals↗
PubMed1999

Eosinophilic alveolitis in BAL after lung transplantation.

Lung transplantation has become a therapeutic option for patients with end stage lung disease. However, outcome after transplantation is complicated by episodes of rejection and infections. Bronchoalveolar lavage is a valuable tool in monitoring patients after transplantation, since it allows the detection of pathogens. A marker specifically indicating rejection from changes in BAL fluid has not been found yet. Especially changes in differential cell count, like lymphocytosis or an increase in polymorphnuclear granulocytes, are unspecific. The role of high eosinophil levels in BAL has not been elucidated yet. We analyzed 25 BAL samples and clinical data of 4 patients who underwent lung transplantation and presented with recurrent episodes of eosinophilic alveolitis in BAL. All patients demonstrated a deterioration of clinical condition, lung function, and blood gas analysis during times of eosinophilia in BAL, compared to previous examinations. In all cases, eosinophilia in BAL was accompanied by rejection. All patients were finally treated with high doses of steroids, resulting in improvement of all parameters. Eosinophilia was not associated with significant changes in the IL-5 concentration in BAL or the pattern of IL-5 expression in BAL cells. In conclusion, eosinophilic alveolitis may indicate acute rejection in patients after lung transplantation, if other causes of eosinophilia are excluded.

Bronchoalveolar Lavage Fluid↗
PubMed1999

Inhibition of adenovirus-mediated gene transfer by bronchoalveolar lavage fluid.

Human and animal trials with recombinant adenovirus have been discouraging, since the level of recombinant gene expression was low. Nonspecific and specific immune response mediated by, for example, macrophages, T cells and immunoglobulins may prevent infection or cause death of infected cells. We analyzed the effect of bronchoalveolar lavage fluid (BAL) on the efficiency of adenoviral infection in vitro. A total of 26 BAL samples of randomly selected patients was examined. Adenovirus-mediated gene transfer was quantified using AdCMV. Null, a recombinant adenovirus, in a modified titer assay based on immunocytochemical detection of infected 293 cells. In addition, the concentration of anti-adenovirus-type 5 IgA, IgG and IgM antibodies in BAL was determined by ELISA. 53.8% of the BAL samples (14 out of 26) reduced adenoviral infectivity by at least 50% (factor of inhibition > or = 2). All BAL samples effecting, a reduction in adenoviral infectivity contained detectable amounts of anti-adenovirus-type 5-IgA antibodies. However, the correlation between the concentration of IgA antibody and the strength of inhibition was weak (r = 0.336). Even high levels of anti-adenovirus-type 5-IgM, IgG or IgA antibodies did not influence adenoviral infectivity consistently. This observation indicates that BAL contains (a) anti-adenovirus-type 5 antibodies which are not directed against adenoviral epitopes responsible for the viral adherence and uptake process; and/or (b) inhibitors of viral infectivity different from antibodies.

Adenoviridae↗
PubMed1999

A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors.

Mutations in the ras genes occur in 20% of all human cancers. These genes, in turn, produce mutated proteins that are unique to cancer cells, rendering them distinguishable from normal cells by the immune system. Thus, mutated Ras proteins may form potential targets for immune therapy. We conducted a phase I/pilot clinical trial in patients with advanced cancers to test the toxicity and the ability to induce an immune response by vaccination with 13-mer mutated Ras peptides reflecting codon 12 mutations. These peptides corresponded to each of the patient's own tumor Ras mutation. Patients were vaccinated monthly x3 subcutaneously with the specific Ras peptide along with Detox adjuvant (RiBi ImmunoChem Research, Inc., Hamilton, MT, U.S.A.) at one of five different peptide dose levels (100, 500, 1,000, 1,500, and 5,000 micrograms). Three out of 10 evaluable patients generated a mutant Ras specific CD4+ and/or CD8+ T-cell immune response. The CD8+ cytotoxic cells specific for Gly to Val mutation at codon 12 were capable of lysing an HLA-A2-matched tumor cell line carrying the corresponding mutant but not the wild-type ras gene. The treatment has been well tolerated with no evidence of serious acute or delayed systemic side effects on any of the five dose levels. We demonstrated that we can generate in cancer patients specific T-lymphocyte responses that detect single amino acid differences in Ras oncoproteins. Neither the immune responses nor the minor side effects seen were found to be dose dependent. This approach may provide a unique opportunity for generating a tumor-directed therapy. Also, in vitro stimulation of these cells with the corresponding peptide generated specific T-cell lines that could be used for adoptive immune therapy.

Adult↗
PubMed1999

Crohn's disease mimicking sarcoidosis in bronchoalveolar lavage.

Granulomatous disorders like sarcoidosis or Crohn's disease are commonly associated with extrapulmonary or extraintestinal manifestations which occasionally may represent the only symptoms. We describe a 28-year-old female patient suffering from atypical erythema nodosum and arthritis. Although the chest x-ray was unremarkable bronchoalveolar lavage revealed lymphocytic alveolitis with an elevated CD4/CD8 ratio of 8 and 11.4 at repeated examinations suggesting a diagnosis of sarcoidosis. Further diagnostic workup included endoscopy of the bowel. The macroscopic aspect and histology of the terminal small bowel and colon ascendens indicated Crohn's disease. The patient recovered on steroids and sulfasalazine. Six months later she developed a perianal abscess for which she needed surgery supporting the diagnosis of Crohn's disease. This is the first case of a significantly (>6) elevated CD4/CD8 ratio in Crohn's disease previously regarded as highly specific for sarcoidosis.

Adult↗
PubMed1998

Prior information preshapes the population representation of movement direction in motor cortex.

Single neuron activity was recorded in monkey motor cortex during the execution of pointing movements in six directions. The amount of prior information was manipulated by varying the range of precued directions. A distribution of neural population activation was constructed in the space of movement directions. This population representation of movement direction was preshaped by the precue. Peak location and width reflected the precued range of movement directions. From this preshaped form, the population representation evolved continuously in time and gradually in parameter space toward a more sharply peaked distribution centered on the parameter value specified by the response signal. A theoretical model of motor programming generated a similar temporal evolution of an activation field representing movement direction.

Animals↗
PubMed1997

Cardiac tamponade--a rare complication in acute pancreatitis.

A patient with recurrent acute pancreatitis developed pericardial effusion and cardiac tamponade. His systolic blood pressure fell to 70 mmHg and sinus tachycardia (150/min) developed. The central venous pressure rose from 3 cm H2O to 27 cm H2O. A chest radiograph showed an enlargement of the cardiac shadow. Pericardial paracentesis was performed and 300 ml fluid was aspirated. This produced rapid clinical improvement. The literature related to this uncommon complication is reviewed and possible pathogenetic mechanisms are discussed.

Acute Disease↗
PubMed1997

A case of Behçet's syndrome presenting with Dieulafoy's ulcer.

Behçet's syndrome represents a multisystemic disease with vasculitic changes. We here describe a patient with Dieulafoy's ulcer and oral, genital and bronchial mucosal lesions who met the criteria of incomplete Behçet's syndrome. The rare observation of Behçet's syndrome presenting with Dieulafoy's ulcer in our patient raises the question as to whether this type of ulcer, usually caused by a developmental malformation of a submucosal gastric artery, may occasionally be due also to submucosal aneurysms that result from a vascular inflammation.

Aged↗
PubMed1996

Chylous cardiac tamponade in acute pancreatitis.

A 47-year-old woman with acute necrotizing pancreatitis developed sudden cardiorespiratory arrest and needed resuscitation. A pericardial effusion was found, and 350 ml of a white nontransparent milky fluid was aspirated that contained 1020 mg triglycerides/100 ml. The diagnosis of chylous cardiac tamponade was made. Absence of amylase in the chylous effusion militates against the popular hypothesis that lymphatic transport of exocrine digestive enzymes from the inflamed pancreas produces the frequent intrathoracic serosal effusions in acute pancreatitis. The data of our patient rather suggest that these effusions result from the leakage of pancreatic inflammatory exudates through the diaphragm which, apparently, may even result in the loss of pericardial and adjacent thoracic lymph vessel integrity. Although pericardial tamponade is a rare complication, it should be considered if otherwise unexplained circulatory deterioration occurs in a patient with acute pancreatitis.

Acute Disease↗