PubMed Health⌕ Search

Biomedical subjects

T K Held

Publications and source records attributed to T K Held.

24 records · Page 2Linked to original sources
PubMed1996

Kinetics and dose dependence of macrophage colony-stimulating factor-induced proliferation and activation of murine mononuclear phagocytes in situ: differences between lungs, liver, and spleen.

Alveolar macrophages (AM) play an important role in antimicrobial defense mechanisms of the lung. It therefore seems reasonable to use macrophage colony-stimulating factor (M-CSF) to enhance local resistance mechanisms. However, little is known about the in vivo activity of M-CSF on macrophages in various organs. We determined the effect of a single subcutaneous dose of M-CSF (10, 50, 100, and 500 ng, respectively) on the number and functional status of AM as well as of macrophages in liver and spleen of mice. Organs were investigated immunohistochemically on days 1 and 3 after injection using monoclonal antibodies specific for F4/80, Ia antigen, and MAC-1. We found a significant increase in the number of F4/80+ AM, Kupffer cells, and splenic macrophages reaching its maximum 24 h after injection of low doses (10 and 50 ng per mouse, respectively) of M-CSF and decreasing to a level seen in untreated mice at 72 h after M-CSF in liver and spleen, whereas at a dose of 50 ng per mouse the number of AM remained high. In contrast, the numbers of AM, Kupffer cells, and splenic macrophages did not increase significantly when high doses were used (500 ng). The expression of Ia antigen and MAC-1 was increased on macrophages in the spleen but not on AM or Kupffer cells. TNF-alpha was elevated in bronchoalveolar (BAL) fluid after 3 h and IL-6 at 6, 12, and 24 h after M-CSF injection in dose-dependent manner. Nitric oxide production was not increased after injection of M-CSF. Our results point to regional differences in the response of macrophages to M-CSF. These may caused by differences in the M-CSF-induced production of TNF-alpha and IL-6. These findings may be important for the therapeutic use of M-CSF in microbial infections.

Animals↗
PubMed1995

Effects of MICs and sub-MICs of antibiotics on production of capsular polysaccharide of Klebsiella pneumoniae.

In the present study, we examined whether MICs and sub-MICs of antimicrobial agents belonging to two different classes, ciprofloxacin and ceftazidime, were able to influence the production and release of cell-associated and soluble (extracellular) capsular polysaccharide (CPS), respectively, in a heavily encapsulated strain of Klebsiella pneumoniae (B5055). Using a CPS-specific enzyme-linked immunosorbent assay, we found that the amount of cell-associated CPS increased in a dose-dependent manner by more than 10-fold under the influence of the MIC of ceftazidime and by more than 100-fold under the influence of the MIC of ciprofloxacin. The largest amounts of CPS were measured by using the MIC of either antibiotic substance. Electron microscopic studies showed that the diameter of the capsule was significantly increased compared with the diameter for untreated controls. Thus, both antimicrobial agents genuinely stimulated CPS production.

Anti-Bacterial Agents↗
PubMed1994

Malaria prophylaxis: identifying risk groups for non-compliance.

To investigate behaviour in the use of drug prophylaxis against malaria and the risk factors for non-compliance, 507 European or North American travelers returning from endemic areas were studied retrospectively at Berlin in a 11-year period from 1980 to 1990. Compliance was significantly correlated with shorter travel duration: the group with good compliance stayed 37.2 +/- 38.5 days (mean +/- SD) in contrast to 69.8 +/- 93.5 days in the group of patients with no compliance (p = 0.00001). Older patients were significantly more compliant than patients aged < 55 years (20/27 compliant at > 54 years vs. 175/476 at < 55 years; p = 0.0001). Compliance was significantly affected by travel destination (Southern and East African regions; p = 0.0054), age (< or = 15 and > or = 55 years, respectively; p = 0.0001), and reason of travel (package tours; p = 0.0001). CART analysis confirmed logistic regression analysis with respect to age and travel type, and revealed that patients using only one information source were significantly more compliant than those using two or more information sources. Travel agencies were nearly as well informed as Institutes of Tropical Medicine, but family doctors had a significant incidence of giving wrong advice. This study should enable medical personnel dealing with prophylactic advice against malaria to identify patients at high risk for non-compliance, and to educate them more carefully than other travellers regarding antimalarial drug prophylaxis.

Adolescent↗
PubMed1992

Monoclonal antibody against Klebsiella capsular polysaccharide reduces severity and hematogenic spread of experimental Klebsiella pneumoniae pneumonia.

Klebsiella pneumoniae is an important nosocomial pathogen causing severe pulmonary infections. The majority of clinical Klebsiella isolates produce a high-molecular-weight capsular polysaccharide (CPS) which is one of the dominant virulence factors. In the present study, we examined the potency of a murine immunoglobulin M monoclonal antibody (MAb) with specificity to Klebsiella type 2 CPS to protect rats against experimental Klebsiella pneumonia. The MAb did not prevent the invasion of virulent bacteria into the interalveolar space. However, the resolution of infection was accelerated in MAb-treated animals. This was demonstrated by (i) less severe weight loss and (ii) markedly reduced inflammatory reactions in the lung. The elimination of bacteria was significantly increased not only in the lungs but also in the livers of antibody-treated rats. This was reflected by reduced levels of circulating, soluble CPS and MAb-bound CPS. A mixture of human MAbs with specificity to CPS of clinically important Klebsiella serotypes may prove to be a useful tool for the prevention or supportive treatment of Klebsiella pneumonia.

Animals↗