Did the gradual loss of GLUT2 cause a shift to diabetic disorders in the New Zealand obese mouse (NZO/Hl)?

The New Zealand obese mouse (NZO/Hl) is characterised by hereditary obesity and type-2 diabetes, including insulin resistance, hyperinsulinaemia, and glucose intolerance. In other diabetic models, it has been revealed that the proper functioning of the glucose transporter isoform 2 (GLUT2) is essential for adequate secretion of insulin. The aim of this study was to compare the distribution of islet cells and GLUT2, as well as the expression of GLUT2-mRNA, in the pancreas of NZO mice and metabolically unimpaired NMRI (Naval Medical Research Institute) mice. Pancreas tissue was obtained from different stages of development. For molecular determination of the expression level of GLUT2-mRNA, total-RNA was extracted from the pancreas and analysed by quantitative real-time RT-PCR. All investigated NZO mice displayed increased weight, elevated hyperinsulinaemia, and slightly enhanced blood glucose levels compared with the NMRI control mice. By means of immunofluorescence microscopy drastically reduced insulin levels were detected, which might be compensated by the observed islet cell hyperplasia and hypertrophy. Furthermore, the normally peripheral localisation of the alpha-cells within islets was disturbed. By contrast, there were no changes in somatostatin cell distribution. However, considerable differences appeared with regard to GLUT2: whereas the beta-cells of NMRI mice showed dense immunostaining of the GLUT2 transporter on the cell surface, in all age groups of NZO mice, GLUT2 on the plasma membranes was reduced and dispersed in the cytoplasm. These findings agree with the molecular biological results, which displayed decreased mRNA-expression of GLUT2. In summary, the observed alteration of islet morphology and of GLUT2 expression in diabetic mice complements our previous results from a superfusion protocol and further clarifies the mechanisms of diabetogenesis in NZO mice.     

Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections.

Levels of the soluble form of the triggering receptor expressed on myeloid cells (sTREM)-1 are elevated in severe sepsis. However, it is not known whether sTREM-1 measurements can distinguish milder bacterial infections from noninfectious inflammation. The present authors studied whether serum sTREM-1 levels differ in community-acquired pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), asthma and controls, and whether sTREM-1 may be used as a surrogate marker for the need for antibiotics. Serum sTREM-1 levels in 150 patients with pneumonia, COPD and asthma exacerbations and 62 healthy controls were measured. Serum sTREM-1 levels were significantly elevated in pneumonia (median 295.2 ng x mL(-1)), COPD (280.3 ng x mL(-1)) and asthma exacerbations (184.0 ng x mL(-1)) compared with controls (83.1 ng x mL(-1)). Levels were higher in pneumonia and Anthonisen type 1 COPD exacerbations than in type 2 and 3 COPD and asthma exacerbations. The area under the receiver operating characteristics curve for sTREM-1 as a surrogate marker for the need for antibiotics was 0.77. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 were elevated predominantly in pneumonia and Anthonisen type 1 COPD exacerbations versus type 2 and 3 chronic obstructive pulmonary disease exacerbations, asthma and controls. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 has moderate but insufficient accuracy as a surrogate marker for the need for antibiotics in lower respiratory tract infections.     

Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype.

We have recently shown that HPV-positive tonsillar carcinoma in young patients exhibits nonkeratinizing basaloid morphology and a characteristic immunophenotype. The purpose of this study was to review a large number of cases of oropharyngeal carcinomas, in all age groups, and to identify tumors with nonkeratinizing morphology. Using polymerase chain reaction (PCR) the prevalence and type of HPV DNA was determined in representative cases and in a control group of conventional keratinizing squamous cell carcinomas. The tumors were further characterized with a panel of immunohistochemical stains. A total of 235 carcinomas were reviewed; 141 of the tonsils and 94 in the base of tongue. Ninety (36%) of the tonsillar and 30 (32%) of the base of tongue carcinomas were nonkeratinizing (NKCa) with basal cell features; the rest were classical keratinizing squamous cell carcinomas (KSCC). HPV DNA, particularly type 16, was identified in 10 (100%) of 10 of NKCA and in only 2 (20%) of 10 of KSCC (P = .0014). NKCas were strongly reactive to p16 antibodies while KSCC showed weak and focal reactivity. Higher Ki67 and lower p53 staining scores were observed in NKCa as compared to KSCC. It is concluded that NKCa of the tonsils and base of tongue is a distinct subtype of squamous cell carcinoma of the head and neck with high prevalence of HPV DNA and a characteristic immunophenotype.     

Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation.

OBJECTIVE: To establish reference intervals for the fetal right, left and total lung volumes and heart volume between 12 and 32 weeks of gestation. METHODS: Fetal lung and heart volumes were measured using three-dimensional (3D) ultrasound in 650 normal singleton pregnancies at 12-32 weeks. The VOCAL (Virtual Organ Computer-aided AnaLysis) technique was used to obtain a sequence of six sections of each lung and the heart around a fixed axis, each after a 30 degrees rotation from the previous one. The rotation axis for the lungs extended from the apex to the upper limit of the diaphragm dome, and the rotation axis for the heart extended from its apex to its connection to the great vessels. The contour of each of these organs was drawn manually in the six different rotation planes to obtain the 3D volume measurement. In 60 cases the fetal lungs and heart volumes were measured by the same sonographer twice and also by a second sonographer once in order to compare the measurements and calculate intra- and interobserver agreement. RESULTS: The total lung volume and heart volume increased with gestation, from respective mean values of 1.6 and 0.6 mL at 12 weeks to 10.9 and 4.3 mL at 20 weeks and 49.3 and 26.6 mL at 32 weeks. The right to left lung volume ratio did not change significantly with gestation (median, 0.7), whereas the heart to total lung volume ratio increased with gestation from about 0.3 at 12 weeks to 0.5 at 32 weeks. In the Bland-Altman plot, the difference between paired measurements by two sonographers was, in 95% of the cases, less than 0.05, 0.5 and 1.9 mL for each lung at 12-13, 19-22 and 29-32 weeks, respectively, and the corresponding values for the heart volumes were 0.04, 0.4 and 2.3 mL. CONCLUSIONS: In normal fetuses the lung and heart volumes increase between 12 and 32 weeks of gestation. The extent to which in pathological pregnancies possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined.