Expression of IL-18 in patients with head and neck squamous cell carcinoma

Interleukin-18 (IL-18), a recently described cytokine secreted mainly by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer cells and T cells. The purpose of this study was to determine tissue expression and serum levels of IL-18 in head and neck squamous cell carcinoma (HNSCC) and to evaluate ethanol and endotoxin-driven cytokine secretion. In 24 patients with primary HNSCC and 28 healthy controls, PBMC were isolated and incubated with 50 mM ethanol, LPS (doses 25 ng/ml, 250 ng/ml, 2500 ng/ml) and both agents for 24 h. Levels of IL-18 in serum, and cell supernatants were analysed by capture ELISA, IL-18 tissue level by immunoblotting. Serum levels of IL-8, IL-10 and IL-12, IFN-gamma, and endotoxin plasma levels were also determined. Statistical analysis involved Welch t-test and Page's test for trend. The majority of patients with HNSCC had high concentrations of serum IL-18. The level of IL-18 in the sera of these patients had a mean level of 271.7 pg/ml, while the mean IL-18 serum level in healthy controls was 174,0 pg/ml (p<0.001). Levels of IL-10 and IL-12, IFN-gamma were not increased in patients. Endotoxin was not detectable in either group. LPS stimulated dose-dependently IL-18 secretion from PBMC of patients and controls in vitro (p<0.05). Incubation with ethanol alone did not affect basal IL-18 secretion, but ethanol reduced LPS-stimulated IL-18 secretion compared to LPS stimulation alone. The mRNA expression of IL-18 in unstimulated PBMC and the response of PBMC to ethanol and LPS was similar in patients and controls. Our data on elevated serum levels of IL-18 in the majority of HNSCC cancer patients, irrespective of its biological activity, suggest that serum IL-18 might be a candidate for a new marker for HNSCC. The pathways for IL-18 production and its mechanisms of action in patients with HNSCC remain to be determined. Understanding of the immunological pathways might offer new therapeutic options in head and neck cancer in the future.     

Die Bedeutung der Tumorpunktion für die Tumordiagnose

Ohne ZusammenfassungMit 5 Textabbildungen.     

Feasibility of Sequential PET/MRI Using a State-of-the-Art Small Animal PET and a 1 T Benchtop MRI

Purpose

Combined PET/MRI studies receive increasing attention, as their combination allows deeper insight into disease progression. We evaluated a novel 1 T benchtop MRI scanner (1T-MRI) for its use in sequential PET/MRI studies.

Procedures

Phantom studies were performed, addressing the attenuation caused by the MRI coils. For in vivo studies, PET/MRI data acquired with the 1T-MRI were compared with data using a conventional small animal high-field MRI (7T-MRI) in combination with the same PET scanner.

Results

Phantom and in vivo measurements show that the animal beds have no negative impact on the PET scanner performance compared to the 7T-MRI animal bed. Representative images of various animal studies are shown, indicating a wide field for sequential PET-benchtop MRI applications.

Conclusion

Phantom and in vivo data indicate that sequential PET/MRI studies with this novel setup are comparable to sequential PET/MRI studies using a 7T-MRI in combination with a dedicated PET scanner.     

Carbohydrate patterns,cellular lipoquinones,fatty acids and phospholipids of the genus Pasteurella sensu stricto

The carbohydrate patterns, isoprenoid quinones, fatty acids and phospholipids of the species of the genus Pasteurella sensu stricto were investigated to evaluate their taxonomic significance and their applicability for the identification of these bacteria. Forty-six representative strains of the 11 species of Pasteurella were examined. The data obtained indicated that the carbohydrate patters are species or subspecies specific and may, therefore, become an important and useful diagnostic tool. Fatty acids and phospholipids showed a feature characteristic of the members of the genus and the isoprenoid quinones exhibited a mostly genus-specific feature with remarkable quantitative differences.     

Phenotypic differentiation ofPasteurella sensu stricto and theActinobacillus group

The current classification of recognized actinobacilli and pasteurellas does not allow differentiation of the two genera by their phenotypic features. Recent investigations of their genetic relationships have shown that several species hitherto assigned to the genusPasteurella are more closely related to the actinobacilli. Moreover, some recently described taxa were located by DNA-DNA hybridization in one or the other of the two genera. On the basis of the genetic system, improved identification keys have been devised which separate the taxonomic groups on the genus and species levels according to an appropriate set of biochemical characteristics.     

Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemia

Vasa vasorum (VV) neovascularization is a key feature of early atherosclerosis and adds substantial endothelial exchange-surface to the coronary vessel wall. Thus, it is conceivable that VV neovascularization favors the entry of pro-inflammatory and pro-atherosclerotic blood components into the coronary vessel wall. We sought to investigate the effects of Thalidomide (Th), a potent anti-angiogenic drug on vasa vasorum (VV) neovascularization, vessel wall inflammation, and neointima formation in early experimental atherosclerosis. Female domestic swine, 3 months old, were fed normal (N, n = 12) or high-cholesterol diet (HC, n = 12) for 3 months. In each group six pigs were randomized to 200 mg Thalidomide daily for the diet period (N + Th, HC + Th). LADs were scanned with micro-CT (20 μm cubic voxel size) to determine VV spatial density (#/mm2). Fresh-frozen coronary tissue was used for western blotting (VEGF, TNF-α, LOX-1, Iκβα and Gro-α) and electrophoretic mobility shift assay (EMSA, NFκβ). Treatment with Thalidomide preserved VV spatial density [2.7 ± 0.3 (N), 6.4 ± 0.7 (HC), 3.5 ± 0.8 (HC + Th); p = ns HC + Th vs. N] and inhibited the expression of VEGF, TNF-α and LOX-1, but not NFκβ activity in the coronary vessel wall. Immunofluorescence analyses revealed co-localization of vWF but not SMA and NFκβ, TNF-α as well as VEGF in HC and HC + Th coronaries. Intima-media thickness was significantly inhibited in HC + Th compared to HC. Serum levels of hs-CRP and TNF-α did not differ among the groups. Our study supports a role of VV neovascularization in the development of and a therapeutic potential for anti-angiogenic intervention in early atherosclerosis.     

Exclusion of growth factor gene mutations as a common cause of Sotos syndrome

Sotos syndrome is characterized by somatic overgrowth, i.e., macrocephaly and tall stature. Because the cause and pathogenesis of Sotos syndrome remain unknown, we selected nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF) and neurotrophin 3 (NT‐3) as possible genes mutated in Sotos syndrome. In seven patients with the classic phenotype, we excluded mutations in these growth factor genes. It is possible that these three genes are not involved in the cause of Sotos syndrome, or alternatively, mutations could not be identified in the small number of patients studied. © 2001 Wiley‐Liss, Inc.