Measurement of activation-related changes in cerebral blood volume: VASO with single-shot HASTE acquisition

Object The recently developed vascular space occupancy (VASO) fMRI technique is gaining popularity as it facilitates the measurement of cerebral blood volume (CBV) changes concomitant with brain activation, without the use of contrast agents. Thus far, VASO fMRI has only been used in conjunction with a GE-EPI (gradient-echo echo planar imaging) sequence, which is proceeded by an inversion recovery (IR) experiment to selectively null the blood signal. The use of GE-EPI has potential disadvantages: (a) the non-zero TE may lead to BOLD contamination and (b) images suffer from the EPI-typical inhomogeneity artefacts. Materials and methods Here, we propose the use of VASO based on an IR-HASTE (inversion recovery half-Fourier acquisition single-shot turbo spin echo) sequence. Results Results from a visual stimulation study (n = 8) show a 43% higher functional contrast-to-noise (CNR) of HASTE compared to EPI, with a strongly increased count of active voxels at the same significance threshold. Sensitivity to inflow effects was investigated and found to be similar for both methods. Conclusion As HASTE VASO yields essentially artefact-free images, it appears to be the method of choice for measuring relative CBV changes with VASO.     

Hilar cholangiocarcinoma: thin-section spiral CT findings with cholangiographic correlation

Hilar cholangiocarcinoma, a highly lethal tumor, is difficult to diagnose with conventional computed tomography (CT) because of its small size. Spiral CT allows more effective evaluation of these small lesions and better demonstrates the status of the hepatic arterial or portal venous circulation. Among 27 patients with hilar cholangiocarcinoma (infiltrative in 21, exophytic in two, polypoid in one, diffuse in three), thin-section spiral CT allowed identification of each tumor as an area of focal wall thickening that obliterated the lumen. Seventeen of the infiltrative tumors (81%) showed high attenuation. Identification of the level of biliary obstruction was possible in 63% of the patients (17 of 27). The level of obstruction was underestimated in six patients and overestimated in four. Spiral CT is a valuable method for diagnosis of hilar cholangiocarcinoma; however, spiral CT is less accurate in evaluation of intraductal tumor extent because of the limited z-axis resolution.     

Fatty acid composition of an oral load affects chylomicron size in human subjects

This paper outlines the demographic characteristics of the Baiga tribe, one of the most primitive of the aboriginal tribal groups of Central India. The Baiga population has grown steadily since the first anthropological study of the tribe in the 1930s. Age at menarche, age at marriage, breast-feeding, and time interval between marriage and first conception are natural. There are more females than males. Sub-tribe endogamy is common; consanguineous marriage is favoured (34% of marriages are between first cousins) and marital distance is low (mean 7.1 km). Though the mean menarcheal age is high (15.2 years), mean age at first marriage is low (16.6 years), giving a long reproductive period.     

Alteration of the cytokine phenotype in an experimental lung granuloma model by inhibiting nitric oxide

Pulmonary granulomatous inflammation modulated by IFN-gamma and IL-12 is also associated with augmented inducible nitric oxide synthase (NOS II). To address the role of increased nitric oxide synthesis in this model, mice received daily i.p. injections of NG-nitro-L-arginine-methyl ester (L-NAME; 8 mg/kg) during both the 2-wk immunization period with purified protein-derivative (PPD) and the subsequent lung challenge with PPD-coated Sepharose beads. Other groups of animals received saline, L-NAME or NG-nitro-D-arginine-methyl ester (D-NAME; 8 mg/kg) during the pulmonary embolization period and not the PPD sensitization period. On day 4 post-PPD bead challenge, PCR analysis of the whole lung revealed that NOS II expression appeared to be similar in both of the L-NAME treatment protocols. L-NAME-treated mice in both dosing protocols had lung lesions that were significantly larger than granuloma lesions measured in mice that received saline or D-NAME. The enlarged lesions from L-NAME-treated mice contained markedly greater numbers of neutrophils and eosinophils. Equivalent numbers of PPD-activated dispersed cells from whole lungs of L-NAME-treated mice produced significantly higher levels of IL-4 and IL-10 and smaller amounts of IL-12 and IFN-gamma compared with similar lung cultures derived from control or D-NAME-treated mice. Levels of C-C chemokines such as monocyte chemoattractant protein-1 (MCP-1), C10, and macrophage inflammatory protein-1alpha (MIP-1alpha) were also significantly elevated in lung cultures from L-NAME-treated mice compared with controls. Thus, nitric oxide regulates the size and cellular composition of the Th1-type lung granuloma, possibly through its effects on the cytokine and chemokine profile associated with this lesion.     

Carcinogenic polycyclic aromatic hydrocarbons increase intracellular Ca2+ and cell proliferation in primary human mammary epithelial cells

A method was developed to determine in eggs 2 components [4,6-dimethyl-2-hydroxypyrimidine and 1,3-bis(4-nitrophenyl)urea] of the anticoccidial drug nicarbazin, used to treat poultry. Samples were extracted with acetonitrile, and the extracts were washed with hexane and evaporated to dryness before analysis by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization. By switching from positive to negative ion monitoring and using gradient elution, both components were measured within one run. The limit of quantitation of the assay was 10 ng/g for each component. The results of a preliminary feeding trial in which chickens were fed contamination levels of the drug are also reported.     

Transgenic models of Huntington's disease

CAG/polyglutamine expansion has been shown to form the molecular basis of an increasing number of inherited neurodegenerative diseases. The mutation is likely to act by a dominant gain of function but the mechanism by which it leads to neuronal dysfunction and cell death is unknown. The proteins harbouring these polyglutamine tracts are unrelated and without exception are widely expressed with extensively overlapping expression patterns. The factors governing the cell specific nature of the neurodegeneration have yet to be understood. Upon a certain size threshold, expanded CAG repeats become unstable on transmission and a modest degree of somatic mosaicism is apparent. Similarly, the molecular basis of the instability and its tissue specificity has yet to be unravelled. Recent reports describing the first mouse models of CAG/polyglutamine disorders indicate that it will be possible to model both the pathogenic mechanism and the CAG repeat instability in the mouse. This has great potential and promise for uncovering the molecular basis of these diseases and developing therapeutic interventions.     

Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in allergic airway inflammation

Allergic airway inflammation is characterized by peribronchial leukocyte accumulation within the airway. Subsequent tissue damage leading to airway hyperreactivity is a result of activation of multiple leukocyte populations. Using an established model of allergic airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg Ag in presensitized mice, we have examined differential leukocyte recruitment. These studies have identified key chemokines involved in the accumulation of specific subsets of cells and the induction of airway hyperreactivity. In this study we have examined three C-C family chemokines, MCP-1, MIP-1alpha, and RANTES, which promote mononuclear cell- and eosinophil-specific recruitment to the airway. The in vivo neutralization of either MIP-1alpha or RANTES, but not MCP-1, significantly reduced the intensity of the eosinophil recruitment to the lung and airway during the allergic airway response by >50 and >60%, respectively. In contrast, neutralization of MCP-1 significantly reduced total leukocyte migration (>50% reduction), whereas neutralization of RANTES and MIP-1alpha had no significant affect on the overall leukocyte migration. Further examination of the effect of MCP-1 depletion indicated that both CD4+ and CD8+ lymphocyte subsets were decreased. Depletion of MCP-1 significantly reduced the airway hyperreactivity to near control levels, whereas depletion of MIP-1alpha or RANTES did not affect the intensity of airway hyperreactivity. These data indicate that multiple C-C chemokines are involved in the recruitment of particular leukocyte populations and that neutralization of MCP-1, but not RANTES or MIP-1alpha, significantly reduced airway hyperreactivity.