Search PubMed⌕ Search

Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

426 records · Page 24Linked to original sources
PubMedDate not supplied

Demonstration of the therapeutic potential of non-anaphylactogenic anti-IgE antibodies in murine models of skin reaction, lung function and inflammation.

BACKGROUND: Allergies and allergic asthma are believed to be mediated by allergen-specific IgE antibodies. We have investigated the therapeutic potential of inhibiting endogenous IgE by a non-anaphylactogenic anti-mouse IgE antibody 1-5 with respect to its effects on antigen-induced skin reaction, lung function changes and lung inflammation in mice. METHODS: Mice were immunized with benzylpenicillinoyl-KLH or ovalbumin, and antigen-mediated skin reaction, bronchoconstriction, bronchopulmonary hyperresponsiveness (BHR) and lung eosinophilic inflammation determined in anti-IgE 1-5-treated versus untreated animals. RESULTS: Application of anti-IgE 1-5 inhibited (by 90%) the serum IgE and, 3-4 days after onset of treatment, blocked the antigen-induced skin reaction. Furthermore, the antibody also inhibited (by 90%) the antigen-induced infiltration of eosinophils into the lung. This latter effect seems to be mediated by blocking the IgE-CD23 interaction and indicates that lung eosinophilic inflammation also depends on IgE. Moreover, when applied to rats passively sensitized with mouse IgE, antibody 1-5 inhibited the antigen-induced bronchoconstriction. A similar effect could be seen in actively immunized mice, where antibody 1-5 was able to inhibit (by 70%) the ovalbumin-induced bronchoconstriction as well as BHR. CONCLUSIONS: In summary, non-anaphylactogenic anti-IgE antibodies can markedly inhibit IgE levels and IgE-mediated allergic reactions. Since bronchoconstriction, BHR and lung eosinophilic inflammation can be suppressed, such antibodies may be attractive principles for the treatment of allergic asthma.

Animals↗
PubMedDate not supplied

Effect of glutamine on protein synthesis in isolated intestinal epithelial cells.

The influence of glutamine on protein synthesis in small-bowel enterocytes was tested. Enterocytes were isolated from different levels of the villi of rat jejunum and were incubated in the presence of different glutamine concentrations, up to 3.4 mmol/L. Protein synthesis was determined by measuring incorporation of 3H-phenylalanine into trichloroacetic acid-precipitated proteins. Glutamine, but no other amino acids, stimulated protein synthesis in enterocytes from all levels of the villi. A maximal effect was noted at a glutamine concentration of 0.67 mmol/L, which is the normal plasma concentration. The amino acid stimulated the synthesis of both secreted and nonsecreted proteins. The stimulatory effect of glutamine on protein synthesis was blocked by the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine and was duplicated by equimolar concentrations of acetoacetate or 3-hydroxybutyrate. The results suggest that glutamine stimulates protein synthesis in small-bowel enterocytes and that this effect of glutamine is related to provision of energy. The findings are important because they suggest that increased protein synthesis may be one of the mechanisms by which glutamine exerts its protective effect on gut mucosa during critical illness.

Animals↗
PubMedDate not supplied

Adoptive immunotransfer with viable donor mononuclear cells for recurrent chronic myelogenous leukemia after allogeneic bone marrow transplantation in two children.

Two children with Ph+ chronic myelogenous leukemia (CML) relapsed in the chronic phase after allogeneic bone marrow transplantation (BMT). They were treated with transfusions of peripheral blood mononuclear cells (PBMC) obtained from the former bone marrow donors in combination with interferon alfa-2. In one child, CML was successfully controlled as shown by disappearance of Ph+ metaphases as well as negativity for BCR-ABL fusion gene transcripts demonstrated by polymerase chain reaction (PCR) analysis. The patient has remained in complete remission without evidence of disease for 12 months after donor PBMC transfusions. The other child showed disappearance of BCR-ABL gene transcripts by PCR analysis only in peripheral blood cells, but PCR positivity persisted in bone marrow samples. These results indicate that adoptive immunotherapy may be a further alternative in children with relapse of CML after allogeneic BMT as previously described for adult patients.

Adolescent↗
PubMedDate not supplied

Adjuvant high-dose chemotherapy with epirubicin and ifosfamide in nodal positive breast cancer.

INTRODUCTION: Morbidity and mortality, disease-free- and overall survival were analysed in an adjuvant high-dose chemotherapy (HDCT) study with ifosfamide and epirubicin for high-risk (> or = 10 positive lymph nodes) breast cancer. PATIENTS AND METHODS: A total of 21 patients (pts) were treated with 4 cycles of ViEC (vindesine, epirubicin, cyclophosphamide) as standard chemotherapy. After the second cycle, CD34+ stem cells were mobilised with G-CSF. HDCT consisted of epirubicin 100 mg/m2 on days (-5)-(-4) before stem-cell rescue and ifosfamide 5000 mg/m2 on days (-5)-(-2). RESULTS: No therapy-related deaths occurred. Mucositis WHO grade III/IV in 52% and neutropenic fever in 81% were the most relevant toxicities. Nausea and vomiting WHO grades III/IV were found in 62.2%. The median duration of leucopenia grade IV was 7 days (range: 4-11) with a median time to platelet recovery > 50,000/microliter of 6 days (range: 4-11). After a median follow-up time of 21 months (range: 12-49 months), six of 21 pts (28.6%) relapsed. Two patients died 12 and 18 months after initial diagnosis. CONCLUSIONS: Adjuvant HDCT with epirubicin and ifosfamide is safe and shows good tolerability for high-risk breast cancer.

Adult↗
PubMedDate not supplied

Amelioration of postischemic acute renal failure by prostacyclin analogue (iloprost): long-term studies with chronically instrumented conscious dogs.

The potential therapeutic value of the chemically stable carbacyclin analogue iloprost on the course of postischemic acute renal failure was studied in six conscious chronically instrumented dogs and compared with five controls. Immediately after temporary ischemia (180-min cessation of blood flow by inflation of a pneumatic cuff), the investigational group PC received a continuous intraaortal infusion of iloprost (50 ng X min-1 X kg-1) over a period of seven days, whereas the control group C received 0.9% saline. The glomerular filtration rate [( 51Cr]EDTA clearance, endogenous creatinine clearance) was less decreased in the prostacyclin analogue group than in the control group [3rd day, 18 +/- 2.5 vs. 12 +/- 1 ml X min-1 (p less than 0.05); 7th day, 23 +/- 3 vs. 12 +/- 2 ml X min-1 (p less than 0.05)]. On day 1, renal blood flow (electromagnetic flow probe) was markedly lower in the control group (129 +/- 29 ml X min-1) than in the PC group (212 +/- 29 ml X min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+136%) was abolished in the PC group (-32%; p less than 0.01). Nitrogen retention was also markedly improved. Osmolar clearance was markedly lower in the control group (0.58 +/- 0.2 ml X min-1) than in the PC group (1.41 +/- 0.17 ml X min-1; p less than 0.05). It is suggested that the beneficial effect of iloprost is mediated by preservation of renal perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMedDate not supplied

Influence of prostaglandin A1 on renal filtration, hemodynamics and excretion. Investigations in chronically instrumented conscious dogs on a low- and high-sodium diet.

The effect on renal function of a 210-min infusion of PGA1 into the aorta of 10 conscious beagle dogs has been investigated. In the sodium-replete group, PGA1 caused an increase in the glomerular filtration rate (GFR) (24%), renal blood flow (17%) and sodium excretion (20%). By contrast, in the sodium-depleted group, PGA1 caused a considerable reduction of GFR (25%) and sodium excretion (51%). In this group, baseline renal blood flow was lower, and there was no further reduction during PGA1 infusion. Fractional sodium excretion was unchanged in the sodium-replete dogs, but was reduced in the sodium-deplete state. Plasma renin activity was markedly elevated and further increased in the sodium-deplete group, but it was nearly unchanged in the sodium-replete group. This difference in renal response to exogenous PGA1 might be due to interaction with the renin-angiotensin system, which was markedly stimulated by sodium depletion and additionally by prostaglandin infusion.

Animals↗