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Biomedical subjects

W Graninger

Publications and source records attributed to W Graninger.

At least 127 records · Page 7Linked to original sources
PubMed1996

Microfilarial clearance in loiasis involves elevation of Th1 and Th2 products and emergence of a specific pattern of T-cell populations.

Diethylcarbamazine (DEC) induced clearance of microfilaraemia in loiasis is associated with severe posttreatment reactions. To define the switch from hypo- to hyper-responsiveness associated with DEC treatment, phenotypic alterations of T-lymphocytes, characterized by flow cytometry, and cytokines, determined by enzyme linked immunosorbent assay, were monitored in a microfilaraemic patient. In contrast to reports on onchocerciasis and lymphatic filariases, no elevation of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha was observed. The most severe side effects coincided with an elevation of interferon (IFN)-gamma on day 3, followed by IL-10, transforming growth factor (TGF)-beta 2 and macrophage inflammatory protein-1 alpha (MIP-1 alpha) peaking on day 5. Phenotypically, T-cell activation markers CD38, CD54 and CD25 were significantly expressed before treatment, with high CD38 expression still existing one year after clearance of microfilaraemia. Treatment-related increases were observed with anti-CD122, anti-HLA-DR and anti-CD69. CD28 was expressed before treatment on almost 100% of CD4+ and CD8+ T cells and dropped to 20% by day 5, reaching again baseline levels on day 21. Furthermore, there emerged 20% TCR alpha beta+/CD3+ T cells and 10% anti-beta V5(c)+ T cells, altogether indicating a specific pattern of T-helper (Th) 1 and Th2 cytokines as well as expansion of certain pauciclonal T-cell populations in response to microfilarial clearance.

Adult↗
PubMed1996

Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.

Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.

Adult↗
PubMed1996

Detection of anti-neutrophil cytoplasmic antibodies after acute Plasmodium falciparum malaria.

Four of 30 patients with Plasmodium falciparum infection in Bangkok, Thailand, were positive for anti-neutrophil cytoplasmic antibodies by indirect immunofluorescence 1 month after antimalarial therapy. No myeloperoxidase, proteinase 3, lactoferrin, or elastase reactivity was found. Since no evidence of vasculitis was seen in these patients, anti-neutrophil cytoplasmic antibody production in malaria-infected susceptible patients probably represents a secondary response, indicating neutrophil activation.

Acute Disease↗
PubMed1996

High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood.

Adult↗
PubMed1996

Increased serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease.

AIM: To measure serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease (PAOD) Fontaine stages IIb, III, and IV. METHODS: The study population comprised 38 patients (20 men and 18 women) with stage IV PAOD, 11 patients (six men and five women) with stage III PAOD, 18 patients (10 men and eight women) with stage IIb PAOD, and 23 patients (10 men and 13 women) with deep vein thrombosis. Fifteen normal subjects (matched for risk factors) and 10 patients (five men and five women) without PAOD served as controls. Serum samples were obtained at admission and serum laminin and angiogenin concentrations were measured using an enzyme linked immunosorbent assay. RESULTS: Patients with stage IV PAOD had higher serum laminin (mean +/- SEM; 826 +/- 97 ng/ml) and angiogenin concentrations (467 +/- 26 pg/ml) than normal subjects (laminin: 379 +/- 21 ng/ml; angiogenin: 358 +/- 16 pg/ml) and patients without PAOD (laminin: 277 +/- 34 ng/ml; angiogenin: 406 +/- 25 pg/ml). A significant correlation was found between angiogenin and laminin and between serum laminin and fibrinogen concentrations in patients with stage IV disease. CONCLUSIONS: Raised laminin and angiogenin concentrations may be indicators of endothelial damage caused by reduced vascular perfusion or compensatory revascularisation, or both.

Angiogenesis Inducing Agents↗
PubMed1996

Quinolones in gastrointestinal infections.

Fluoroquinolones are efficient antimicrobial drugs for the treatment of enteric fever, shigellosis, Escherichia coli diarrhea, cholera, and traveler's diarrhea. They also play a role in the therapy of yersiniosis, campylobacteriosis, and intestinal salmonellosis. A single dose of quinolones has been effective in the treatment of traveler's diarrhea and cholera. Uncomplicated typhoid fever was cured by norfloxacin, pefloxacin, and ofloxacin 400 mg twice daily (b.i.d.) for 7-14 days or ciprofloxacin 500 mg b.i.d. for 10 days. A single daily dose of 400 mg fleroxacin for 3 days has been shown to be effective in this indication. A few reports suggest that the newer quinolones can eliminate the carrier state. The efficacy of quinolones in the prophylaxis and treatment of intra-abdominal infections following abdominal surgery requires further investigation.

Anti-Infective Agents↗
PubMed1996

Angiotensin-converting enzyme polymorphism in patients with terminal renal failure.

An insertion/deletion polymorphism has been described for the gene that encodes the angiotensin-converting enzyme. The deletion allele is associated with higher angiotensin-converting enzyme plasma levels, which ultimately might lead to increased angiotensin II concentrations. Because angiotensin II is a mediator for progressive renal injury, this study determined the frequency of distribution of the angiotensin-converting enzyme insertion/deletion polymorphism in 106 hemodialysis patients and in a group of 95 healthy control patients. There was no difference between the two groups as far as the distribution of the insertion and deletion allele was concerned. Of the total hemodialysis population, 26.4% exhibited the deletion/deletion genotype, as compared with 37.9% of the healthy control population. Also, when patients with terminal renal failure as a result of glomerular disease were analyzed separately, the frequency of the deletion/deletion genotype was identical to that of the control group. Furthermore, the frequency of hypertension, coronary artery disease, left ventricular hypertrophy, and dilated cardiomyopathy, were analyzed according to the angiotensin-converting enzyme genotype, but the deletion allele could not be defined as a risk factor in the study's hemodialysis population. It was therefore concluded that the angiotensin-converting enzyme insertion/deletion polymorphism is not a major risk factor for development of end-stage renal failure. Additionally, in hemodialysis patients, there is no association between the risk for cardiovascular diseases and the angiotensin-converting enzyme genotype.

Adult↗
PubMed1996

Serum levels of erythropoietin in acute Plasmodium falciparum malaria.

The pathophysiologic backgrounds of anemia in malaria are complex and multifactorial. The purpose of the present study was to measure serum concentrations of erythropoietin (EPO) and to evaluate the adequacy of EPO production in patients suffering from acute Plasmodium falciparum malaria. Fifteen patients with complicated malaria were included in the study. Serum samples were taken on the day of admission, and days 7, 14, 21 and 28. Serum EPO concentrations were measured using an enzyme-linked immunosorbent assay. The median serum EPO concentration was 15.6 mU/ml on the day of admission (range 0.5-567) mU/ml, 10.6 mU/ml (1.2-863) on day 7, 11.8 mU/ml (0.5-72.8) on day 14, 10 mU/ml (0.5-74.6) on day 21, and 8.3 mU/ml (2.2-61.6) on day 28. Inadequate EPO production was found in 46.6% of the patients on the day of admission, which increased to 67% and 68% on days 7 and 14, and reached a maximum of 80% on day 21. Almost 54% of patients had inadequate EPO production on day 28. Our data indicate inadequate EPO production in patients suffering from acute P. falciparum malaria, which might contribute to the prolonged anemia observed in these patients.

Acute Disease↗
PubMed1996

Fine specificity of anti-Ro(SSA) autoantibodies and clinical manifestations in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the fine specificity of the anti-Ro(SSA) autoimmune response in patients with systemic lupus erythematosus (SLE), and to correlate it with clinical and serological manifestations. METHODS: The frequency of anti-Ro and anti-La autoantibodies was determined by double immunodiffusion (DID), ELISA, and immunoblotting (IB) in 69 patients with SLE and 39 controls. Protein and RNA immunoprecipitation were used to further characterize anti-Ro positive sera. RESULTS: Anti-Ro antibodies were detected in 37 (54%) patients: 33 (48%) were positive by DID, 35 (51%) by ELISA, and 25 (35%) by IB; 32 sera were reactive in at least 2 of these 3 assay systems. By IB, 12 patients had antibodies to both the 60 kDa Ro (Ro60) and the 52 kDa Ro (Ro52), 11 patients were anti-Ro60 positive, 2 patients were anti-Ro52 positive, and 12 patients were not reactive with blotted Ro antigens. However, in immunoprecipitation assays all but one anti-Ro positive sera precipitated both Ro proteins. Anti-La reactivities were found in 15 anti-Ro positive patients: 13 sera were positive by IB, 11 by ELISA, and 9 by DID. Significant associations of anti-Ro antibodies with clinical symptoms were found for sicca syndrome, which was increased in anti-Ro positive patients (p < 0.05 vs anti-Ro negative patients), and for nephritis, for which an inverse correlation was found, since it was less frequently diagnosed in anti-Ro positive patients (p < 0.01). However, this association was seen only for those anti-Ro positive patients who were not reactive with Ro52 by IB. No difference was observed between anti-Ro/La and anti-Ro positive patients. CONCLUSION: DID and ELISA were of comparable sensitivity for detection of anti-Ro, IB was the most sensitive method for detection of anti-La. Moreover, our data indicate that IB may help to characterize clinically distinct subgroups of anti-Ro positive patients with SLE. Thus, determination of anti-Ro by IB may increase the prognostic value of this autoantibody.

Adolescent↗
PubMed1996

[Aggressive therapy of highly active systemic lupus erythematosus].

Life-threatening exacerbations of systemic lupus erythematosus can endanger the function of vital organ systems and require massive immunosuppressive treatment after the diagnostic delineation of the situation. In addition to high dosages of corticosteroids, the introduction of high dose intravenous cyclophosphamide has improved the prognosis of organ function in SLE in the past years. The concept of plasmapheresis has been left in most centers, although in vitally dangerous situations the application of selective immunoglobulin removal techniques (immunoabsorption) has been reported to be beneficial. The long-term treatment following the acute exacerbations has to consider the side effects of all immunosuppressive drugs like infections and neoplasia, although the danger of another autoaggressive attack of the patient's own immune system has to be kept in mind.

Adrenal Cortex Hormones↗
PubMed1995

[African eye worm as initial manifestation of loaiasis].

HISTORY AND CLINICAL FINDINGS: A 23-year-old woman suddenly had the sensation of a foreign body in her right eye. On looking into the mirror she saw what looked like a moving worm-like structure in the lateral angle of the eye. The patient had visited Cameroon 2 years previously. TESTS: On ophthalmological examination with a slit-lamp a transparent worm, 6-7 cm long, was seen. Laboratory tests showed an eosinophilia of 13%, C-reactive protein slightly raised to 1.25 mg/dl and IgG of 2100 mg/dl (IgE was normal at 33 U/ml). Giemsa staining of a whole-blood drop contained numerous microfilaria typical of Loa loa (2000/ml). Filaria serology with antigen of Dipetalonema vitae (Acanthocheilonema) gave a positive response. TREATMENT AND COURSE: The worm was removed surgically and, after a test dose, diethylcarbamazine, 6 mg/kg daily), was administered. Although methylprednisolone (initially 20 mg daily) was given concurrently, a fever of 38,5 degrees C developed on the 4th day. At the same time, streaky cutaneous eruptions were noted over the left lower arm and left knee bond. These two signs, which were due to two adult worms, disappeared within 2 days. On the 5th day the patient complained of headache, nausea and sensitivity to light, and she had meningism. The symptoms were treated with paracetamol and diazepam and quickly improved. The patient was discharged after 3 weeks. Further treatment cycles with diethylcarbamazine are planned.

Acetaminophen↗
PubMed1995

Purification of human basophils and mast cells by multistep separation technique and mAb to CDw17 and CD117/c-kit.

Basophils and mast cells represent distinct cell lineages within the hemopoietic system. Based on the unique cell surface antigen profile of both cells, we have established methods which allow the reproducible purification to homogeneity (> 99%) of normal human basophil granulocytes from the peripheral blood and of mast cells from human dispersed tissues. Basophils (n = 9) were purified by current counterflow elutriation followed by depletion of monocytes with CD14 mAb conjugated to magnetic beads, and subsequent cell sorting for CD217+ cells. Basophil purity was 99.5 +/- 0.4% (range 98.7-99.9%). Mast cells were obtained from lung (n = 6), uterus (n = 1), mastocytosis bone marrow (n = 2), and human foreskin (n = 2). Mast cells were purified by collagenase digestion followed by current counterflow elutriation and sorting with CD117/c-kit mAb. Mast cell purity was 99.4 +/- 0.7% (range: 97.5-99.9%). Purified cells were more than 90% viable and were able to release histamine on induction with IgE plus anti-IgE. Furthermore, the PCR technique could be applied on pure cells and confirmed expression of high affinity IgE receptor (Fc epsilon R1) alpha chain mRNA. Thus, by combining isolation techniques including elutriation, magnetic cell depletion and cell sorting with mAb, functionally intact normal human basophils and mast cells can be enriched to homogeneity.

Antibodies, Monoclonal↗
PubMed1995

Autoimmune response to the spliceosome. An immunologic link between rheumatoid arthritis, mixed connective tissue disease, and systemic lupus erythematosus.

OBJECTIVE: To assess the significance of autoantibodies to RA33, the A2 protein of the heterogeneous nuclear ribonucleoproteins (hnRNP), and to the related hnRNP proteins A1, B1, and B2 in rheumatic diseases. METHODS: Using a partially purified preparation of hnRNP-A and hnRNP-B proteins, sera from 303 patients with various rheumatic diseases were investigated by immunoblotting. For the analysis of cross-reactivities, autoantibodies were affinity purified by blot elution. RESULTS: Anti-A2/RA33 was found in 35% of rheumatoid arthritis (RA) patients, 38% of mixed connective tissue disease (MCTD) patients, 23% of systemic lupus erythematosus (SLE) patients, and, apart from single exceptions, not in patients with other rheumatic diseases. All anti-A2/RA33-positive sera were also reactive with B1 and B2, and anti-A2/RA33 antibodies cross-reacted with both proteins. Antibodies to hnRNP-A1 were found less frequently; moreover, the majority of anti-A1-positive sera also contained anti-A2/RA33 antibodies. In anti-A1, anti-A2/RA33 double-positive sera, cross-reactivity between the 2 antibodies was generally observed. In SLE patients, the presence of anti-A2/RA33 was correlated with the presence of anti-(U1) small nuclear RNP (snRNP) and anti-Sm (P < 0.0001 and P < 0.005, respectively), but there was no evidence for cross-reactivity between antibodies to hnRNP and antibodies to snRNP antigens. CONCLUSION: Since both hnRNPs and snRNPs are essential components of the spliceosome, the data show that the immune systems of patients with RA, SLE, and MCTD react to this functional complex. However, compared with MCTD and SLE patients, RA patients have a more restricted immune response to the spliceosome: they react to hnRNP proteins, particularly to hnRNP-A2/RA33, but not to snRNPs.

Arthritis, Rheumatoid↗
PubMed1995

Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria.

Serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were determined in 37 patients with acute Plasmodium falciparum malaria in Bangkok, Thailand. Serum levels of IL-10 and IFN-gamma were markedly elevated in patients with malaria prior to treatment (717 +/- 260 pg/ml versus 2.2 +/- 1.3 pg/ml in healthy controls; 123 +/- 71 pg/ml versus 29 +/- 9 pg/ml, respectively; mean +/- SD). Serum levels of IFN-gamma and IL-10 dropped significantly during treatment and were normal 14 and 21 days, respectively, after treatment was started. Prior to therapy a correlation between serum levels of IFN-gamma and IL-10 existed (r = 0.563). These results suggest that stimulatory and inhibitory cytokines for macrophage activation and/or antibody production (i.e., TH1- and TH2-type immunoreaction, respectively) are coexpressed during acute P. falciparum infection and stress the multifactorial network between host and parasite in malaria immunology.

Acute Disease↗
PubMed1995

Serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen and laminin are elevated in Graves' disease but not in toxic nodular goiter.

We determined serum levels of laminin, carboxy-terminal cross-linked telopeptide, and carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 27 patients with Graves' disease (GD) and in 31 patients with toxic nodular goiter (TNG). Elevated levels of soluble laminin and ICTP were observed in patients with GD prior to treatment (mean +/- SD concentration 1444 +/- 404 and 8.6 +/- 3.5 ng/ml, respectively), compared to patients with TNG (476 +/- 103 and 4.2 +/- 1.5 ng/ml) and normal controls (492 +/- 112 and 3.1 +/- 1.3 ng/ml, n = 34). In contrast, serum PICP concentrations were not different between patients with GD or TNG and normal controls. In GD patients serum ICTP and laminin levels decreased during thiamazole treatment and normalized within 4 and 8 weeks of therapy. There was no correlation between serum ICTP and laminin levels and serum levels of thyroid hormones and/or autoantibodies, respectively. Serum ICTP and laminin could be markers for alterations of extracellular matrix during GD and release of matrix components in the circulation and/or reflect an impaired clearance.

Adult↗
PubMed1995

Serum concentrations of MIP-1 alpha and interleukin-8 in patients suffering from acute Plasmodium falciparum malaria.

The chemokines are a superfamily of small proteins secreted primarily by leukocytes and related by a conserved four-cystein motif. In the present study we investigated the serum levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-8 (IL-8). MIP-1 alpha is a neutrophil chemotactic protein important in acute and chronic inflammation. Recent studies demonstrated that MIP-1 alpha may also act as potent inhibitor of hemopoetic stem cell proliferation, which may be important in the development of prolonged anemia in patients suffering from Plasmodium falciparum malaria. IL-8 serum concentrations correlate with severity and outcome of infectious diseases. Moreover, recent reports indicate that IL-8 plays a major role in fatal gram-negative sepsis. It was the aim of this study to investigate the time course of MIP-1 alpha and IL-8 concentrations in patients suffering from acute P. falciparum infection. Blood samples of 20 patients suffering from severe P. falciparum malaria were investigated. MIP-1 alpha and IL-8 concentrations were determined using ELISA technique at admission, on Days 7, 14, 21, and 28. Maximal concentrations of MIP-1 alpha and IL-8 were found on Day 14, at a time when parasites were not detected in the smears. The serum levels of IL-8 on the day of admission were correlated to the parasite count. No correlation was seen between the hematokrit values and the MIP-1 alpha concentrations at any time.

Adolescent↗