Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma.

Members of the lysyl oxidase family (LOX) are copper and lysyl-tyrosine quinone cofactor-containing amine oxidases that are important for the assembly and maintenance of components of the extracellular matrix. Our previous results demonstrated that a novel member, LOXL4, is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. Results of the current study showed overexpression of the LOXL4 transcript in 74% (46 of 62) of invasive HNSCC tumours and 90% of both primary and metastatic HNSCC cell lines. Significant correlation was found between LOXL4 expression and local lymph node metastases versus primary tumour types (p<0.01) and higher tumour stages (p<0.01). Immunocytochemistry demonstrated cellular overexpression of the LOXL4 protein that correlated with the increased mRNA transcription in HNSCC cells. HNSCC cell lines displayed in significant subset of nuclei increased copies of the LOX4 gene locus on chromosome 10q24, demonstrated by fluorescence in situ hybridization (FISH). Extensive metaphase cytogenetic analysis was performed on UTSCC19A cells, identifying an isochromosome i(10)(q10). Taken together, these results highlight LOXL4 expression as a distinctive trait and suggest a functional role for LOXL4 in the molecular pathogenesis of invasive head and neck carcinomas.

[Acute airway obstruction in acquired hemophilia A]. / Akute Atemwegsverlegung durch erworbene Hämophilie A.

We report the case of a 67 year old patient suffering from acute airway obstruction caused by hemorrhage localized to the tongue, mouth cavity and hypopharynx, with no evidence of bleeding in his history. The patient presented initially with a globus feeling of the neck, dysphagia and a sore throat. CT scan revealed a swelling of the lingual and sublingual areas and the pharyngeal wall. Next day, there was an immediate life-threatening event caused by progressive bleeding with airway obstruction and an inability to intubate requiring coniotomy. The etiology of the hemorrhage was confirmed by finding a depletion of factor VIII and the presence of auto-antibody directed against this factor. Based on this case report and a review of the literature, we discuss the diagnosis and treatment of acquired hemophilia.

A newly discovered function of palatine tonsils in immune defence: the expression of defensins.

The palatine tonsils have an undoubted role in the immune defence system. After antigen contact an effective adaptive immune response by B- and T-cell lymphocytes will be released. In addition the palatine tonsils seem to exert influence to the defence by the innate immune system. Therefore, we studied the ability of palatine tonsils to express different alpha and beta defensins and to find out any distinctions in chronic inflamed tonsils. Total RNA of 49 specimens of hyperplastic tonsils and chronic tonsillitis with pathological provided evidence of Actinomyces israelii was isolated using TRIzol protocol, reverse transcribed and the HNP-1, HNP-4, HBD-1 and HBD-2 gene expression densitometric determined, standardised in relation to glycerinaldehyd-3-phosphatdehydrogenase gene expression, after a semiquantitative polymerase chain reaction was performed. mRNA of HNP-1, HNP-4, HBD-1 and HBD-2 was detected in tissue samples, but their amount differed within the two defensin families and tissue of origins. HBD-1 was detected in all 49 tissues of hyperplastic tonsils and chronic tonsillitis. Only in chronic inflamed tonsils the amount of HBD-2 mRNA expression was significant increased. In these specimens also mean relative expression rate of all defensins was observed to be manifestly increased. Palatine tonsils express mRNA for different alpha and beta defensins and this expression suggest a newly supposed function in immune defence: the participation in the innate, non-adaptive immune system. Thus, palatine tonsils have a potentially influence in the growth and control of the physiological mouth bacteria by their bactericidal activity.

A comparative study of chemokine rantes detection using ELISA and Western blot.

Chemokines in biological sample are frequently found at very low level. Further, concentrations of chemokines which were measured in the same tissue detected with different methods often differ in literature. Therefore, RANTES concentrations were quantified by application of sandwich enzyme-linked immunosorbent assay (ELISA) and Western blot analyses. The sensitivity of ELISA was found to be much higher than that of Western blot. Additionally, the detection time differed considerably as well. For biological and biochemical characterization of chemokines it is essential to implement the optimal purification and detection techniques. With an understanding of the technical procedures and some pitfalls, chemokine detection can be applied more reliably.

Transcranial Doppler sonography in adult hydrocephalic patients.

Transcranial Doppler sonography (TCD) is a noninvasive technique for measurement of cerebral blood flow velocity (CBFV) in the major arteries of the circle of Willis. Dynamic changes in the pulsatility index (PI) and the resistance index (RI), as calculated from TCD data, allow for an assessment of the forces acting on the terminal vasculature of the brain. The present study was designed to investigate a possible relationship between TCD parameters and intracranial pressure (ICP) changes in adult patients with hypertensive hydrocephalus. Blood flow velocity in the middle cerebral artery (MCA) was studied by TCD in 29 hydrocephalus patients and in 20 healthy controls. ICP was measured in the patient group before ventricular shunting and was correlated with TCD data. The mean CBFV in hydrocephalic patients prior to ventriculoperitoneal shunting was significantly lower than in the control group. Compared to normal persons, systolic and end-diastolic CBFV values in patients were significantly decreased, suggesting an increased distal cerebrovascular resistance. PI and RI values in patients with elevated ICP prior to shunting were significantly increased in comparison to those of normal persons. There was a statistically significant positive correlation of preshunting ICP and mean preshunting values of RI (r=0.50, P<0.01) in hydrocephalic patients, but no significant correlation between PI and ICP, and between CBFV and ICP. Immediately after shunting, ICP returned to normal, and PI and RI values decreased significantly, while the mean CBFV increased. In a subgroup of hydrocephalic patients with a preshunting ICP value >35 mm Hg (n=6), the changes described above were more pronounced than in the subgroup with preshunting ICP values <35 mm Hg, which suggests an exponential degree of influence of ICP on TCD parameters. In conclusion, TCD may provide a tool for assessment of ICP in adult patients with occlusive hydrocephalus, although an exact noninvasive measurement of ICP by TCD seems impossible. Changes in the RI and PI indices appear to be useful indicators of elevated ICP.