Effect of lipoteichoic acid on dermal vascular permeability in mice

Lipoteichoic acid (LTA), the cell wall component of Gram-positive bacteria, has been shown to cause inflammatory responses comparable to lipopolysaccharide (LPS) of Gram-negative bacteria. This study examined the activity of LTA to induce dermal microvascular permeability changes in mice. Vascular permeability was assessed by extravasation of Pontamine sky blue. Subcutaneous injection of LTA (200-400 microg/site) in mice that were preinjected i.v. with the dye increased local dye leakage in the skin at 1 to 3 h. The LTA-induced dye leakage was inhibited by indomethacin, valeryl salicylate, diphenhydramine, and a platelet-activating factor antagonist but not by inhibitors of nitric-oxide synthase, cyclooxygenase-2, or guanylate cyclase or by antibodies against tumor necrosis factor-alpha or interleukin-1alpha. LTA induced comparable increases in dye leakage in inducible nitric-oxide synthase-deficient mice and wild-type controls. Pretreatment of normal mice with i.v. LTA did not confer tolerance to LTA- or LPS-induced dye leakage. In contrast, systemic LPS administration induced tolerance against subsequent challenge with LPS but not LTA. Serum corticosterone levels, which were suggested to induce tolerance, were not increased by LTA pretreatment but were increased by LPS. Thus, LTA increases dermal microvascular permeability in mice. Among the inflammatory mediators, eicosanoids, platelet-activating factor, and histamine mediate the effect of both LTA and LPS, whereas nitric oxide, tumor necrosis factor-alpha, and interleukin-1alpha may not play a major role in LTA-induced dye leakage. The difference between LTA and LPS to stimulate corticosterone may partially explain the failure of LTA to induce tolerance against vascular dye leakage.     

Clinical application of a new method that segments the region of interest into multiple layers for RF amplitude histogram analysis in the cirrhotic liver

Purpose We used texture analysis in conjunction with an alternative method of analyzing the amplitude histogram using a radiofrequency (RF) signal to differentiate ultrasonograms of normal and cirrhotic livers. This method segments the region of interest (ROI) into multiple layers (sub-ROIs). In each sub-ROI of a homogeneous medium, the histogram of enveloped-amplitude of RF backscattered echoes resembles a Rayleigh distribution. Theoretically, the values of the signal-to-noise ratio (SNR), skewness, and kurtosis for Rayleigh statistics are constant and independent of the mean scattering intensity, which is contributed by such undesirable effects as tissue attenuation, beam diffraction, and incident waveforms. These values, which averaged overall sub-ROI, should provide an unbiased estimator.Methods We studied 36 normal livers and 28 cirrhotic livers, all confirmed by clinical findings including laboratory and pathology data; the SNR, skewness, and kurtosis values of the disease groups were compared. At the same time, these values were estimated using the conventional method, which did not segment the ROI into multiple sub-ROIs. The unpaired t-test was used to determine statistical significance.Results With the new method, all values obtained from cirrhotic livers differed significantly from those obtained from normal livers, and the standard deviation of these values was smaller than those obtained using the conventional method.Conclusions These results suggest that the new method can be used to diagnose the cirrhotic liver objectively.This article is translated from the Japanese version, which was published in J Med Ultrasonics 2001;28:J25–33     

Ectopically located gonads in a patient with mixed gonadal dysgenesis: detection by diffusion-weighted MRI

We report a case of mixed gonadal dysgenesis in which diffusion-weighted magnetic resonance imaging played a major role in the detection of ectopically located gonads. Magnetic resonance imaging may have a potential in detecting ectopically located gonads and may provide important information for the management of patients with mixed gonadal dysgenesis.     

Molecular targeting drugs--present status and future development

Development of molecular targeting drugs is a recent highlight in cancer therapeutic field. One can look for 'drugable' target(s) from many molecular targets specific in malignant characteristics of human cancers. Drugs targeting various malignancy-linked molecules such as EGF receptor and its family proteins. Bcr-abl, CD20, Ras and others are now approved or under clinical trials against cancer patients. These molecular targeting drugs will provide a novel and useful therapeutic strategy, but, at the same time, we have many problems to overcome. We should continue our further efforts to answer following problems: (1) How therapeutic efficacy of molecular targeting drugs could be determined in patients in evidence-based manner?; (2) What is promising molecular target for development of drug?; (3) How combination therapy of molecular targeting drug with other cytotoxic drugs should be designed?