Minimally invasive therapy under image guidance--emphasizing MRI-guided cryotherapy

Cryotherapy may provide a method for the focal destruction of cancerous tissue while preserving most of the surrounding normal tissue. The mechanisms of tissue injury in cryotherapy are 1) intracellular ice formation, 2) dehydration of cells, and 3) stagnation of microcirculation. MR images were superior to CT and ultrasound in monitoring interstitial cryotherapy, because the very short T2 relaxation time of ice affords excellent contrast between the ice and surrounding tissue, allowing an accurate depiction of the entire extent of the iceball. MR imaging demonstrates the iceball as sharply marginated regions of signal loss that expanded and engulfed the renal and hepatic masses with clear contrast between the iceball and surrounding tissue. Recently, a fast Joule-Thomson cryocycling device for MR-compatible cryotherapy application was developed and clinical trials under MRI-guided monitoring were performed in several sites of the body. In our series, cryotherapy was performed in 14 cases of renal tumor and 4 cases of hepatic malignancy under the guidance of a horizontal open MR system. Fourteen of the 18 cases were discharged a day after cryotherapy. One of the residual tumors at the margin of a renal cancer required re-cryoablation. All cryoablated tumors resolved and there were no serious complications and no clinically significant changes-during the follow-up study.     

De novo interstitial deletion of 1p (pter----p34.1::p32.3----qter).

We report a case of a 9 month old girl with a de novo interstitial deletion of 1p, karyotype 46,XX, del(1)(pter----p34.1::p32.3----qter). She had dysmorphic features including upward slanting palpebral fissures, a bulbous nose, a long philtrum, low set and malformed ears, a short neck, hypoplastic nails on both index fingers, widened interdigital spaces between the toes, dilated lateral ventricles, right hydronephrosis, a dilated right ureter, mental and motor developmental delay, and generalised hypotonia.     

Acanthamoeba-specific human T-cell clones isolated from healthy individuals

T-cell responses to pathogenic free-living amoebae,Acanthamoeba sp., were analyzed in healthy Japanese individuals. Of 20 healthy subjects, 10 (50%) showed significant proliferative responses of peripheral blood mononuclear cells to the soluble amoebic antigens in vitro. The antigens used were not mitogenic, and no evidence of amoebic superantigens was available. We established human T-cell clones reactive toAcanthamoeba, all of which were CD3- and CD4-positive, CD8-negative, and TCR--positive. We isolated two strains ofAcanthamoeba from two patients, one from a patient with meningoencephalitis (CSF strain) and the other from a patient with keratitis (K strain). Of 13 clones, 11 were reactive to the K-strain as well as to the CSF-strain antigen under human leukocyte antigen (HLA)-DR restriction, whereas the other two were specific for the K-strain antigen. All but one clone tested showed TH1-equivalent functions because these cells produced interferon (IFN)- in response to the amoebic antigen but produced no detectable level of interleukin 4 (IL-4). These results suggest that immunocompetent hosts might have acquired protective immunity mediated byAcanthamoeba-specific T-cells during natural sensitization.     

The full expression of the ity phenotype in ityr mice requires C3 activation by Salmonella lipopolysaccharide.

Our previous study has shown that the rapid and sufficient activation of complement by Salmonella lipopolysaccharide occurs in genetically resistant (Ityr) A/J mice. To assess whether the level of complement activation by a virulent strain of Salmonella typhimurium regulates the level of murine natural resistance, we compared levels of serum complement activation by S. typhimurium and kinetics of serum-opsonized S. typhimurium grown in macrophages using several strains of resistant (Ityr) and susceptible (Itys) mice. Itys macrophages killed intracellular S. typhimurium to the same extent as did Ityr macrophages when the pathogen was opsonized with Ityr serum. Opsonization of S. typhimurium with Itys serum reduced intracellular killing activity in Ityr macrophages to the same level as seen with Itys macrophages. Incubation of S. typhimurium with 25% Mg2+ EGTA (5 mm MgCl2-3 mm ethylene glycol-bis (beta-aminotheyl either)-N,N,N',N'-tetraacetic acid)-chelated Ityr serum resulted in higher levels of C3 deposition onto the surface of this bacteria, C3b generation and also C3 consumption, compared with that with Mg2+ EGTA-chelated Itys serum. Opsonization of S. typhimurium with A/J serum prior to infection increased early resistance in Itys mice. Infection with a virulent strain of S. typhimurium induced the expression of interleukin-10 (IL-10) mRNA at higher levels in C57BL/6 mice than in A/J mice. However, opsonization of S. typhimurium with A/J serum decreased bacterial growth in the spleen of C57BL/6 mice to the same level as observed for A/J mice in association with decreased expression levels of IL-10 mRNA. Moreover, administration of anti-C3 antibodies reduced the resistance of A/J mice in association with a decrease in serum levels of C3. These results indicate that the high level of complement activation via the alternative pathway in Ityr serum by a virulent strain of S. typhimurium reduces the virulence of this pathogen, which may contribute to the full expression of Ity phenotype in Ityr mice.     

Use of enzyme-linked immunosorbent assays with chimeric fusion proteins to titrate antibodies against Epstein-Barr virus nuclear antigen 1.

Two new enzyme-linked immunosorbent assays (ELISAs) with chimeric fusion polypeptides for the detection of human antibodies specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1) are described. One is an indirect ELISA with affinity-purified beta-galactosidase-EBNA-1 fusion protein as the antigen. The other is a "sandwich" assay based on the use of anti-beta-galactosidase antibody to capture beta-galactosidase-EBNA-1 fusion proteins in bacterial extracts. A good correlation was shown between antibody titers determined by the ELISA with the EBNA-1 fusion proteins and those determined by a conventional anticomplement immunofluorescence test which is being widely performed with Raji cells for the purpose of research and clinical diagnosis. The advantage of the ELISAs for seroepidemiologic studies on Epstein-Barr virus was demonstrated by sensitive detection of marginal immunoglobulin G antibody to the EBNA-1 domain in serum samples from patients with infectious mononucleosis.     

Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3

The pathogenesis of hepatitis C virus (HCV)-associated insulin resistance remains unclear. Therefore, we investigated mechanisms for HCV-associated insulin resistance. Homeostasis model assessment for insulin resistance was increased in patients with HCV infection. An increase in fasting insulin levels was associated with the presence of serum HCV core, the severity of hepatic fibrosis and a decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central molecules of the insulin-signaling cascade, in patients with HCV infection. Down-regulation of IRS1 and IRS2 was also seen in HCV core-transgenic mice livers and HCV core-transfected human hepatoma cells. Carbobenzoxy-l-leucyl-l-leucyl-l-leucinal, a potent proteosomal proteolysis inhibitor, blocked down-regulation of IRS1 and IRS2 in HCV core-transfected hepatoma cells. In human hepatoma cells, HCV core up-regulated suppressor of cytokine signaling (SOCS) 3 and caused ubiquitination of IRS1 and IRS2. HCV core-induced down-regulation of IRS1 and IRS2 was not seen in SOCS3(-/-) mouse embryonic fibroblast cells. Furthermore, HCV core suppressed insulin-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase and Akt, activation of 6-phosphofructo-2-kinase, and glucose uptake. In conclusion, HCV infection changes a subset of hepatic molecules regulating glucose metabolism. A possible mechanism is that HCV core-induced SOCS3 promotes proteosomal degradation of IRS1 and IRS2 through ubiquitination.     

The cyclo-copolymerization of diallyl compounds and sulfur dioxide, 6. 1,6-Heptadiene and sulfur dioxide

Copolymers from 1,6-heptadiene ( 1 ) and SO₂ with various mole ratios of their units were prepared. Their structures were studied by elemental analyses, IR and ¹H NMR spectroscopy. Structures containing a cyclopentane ring ( 2 ) and such containing a thiane ring ( 3 ) in the main chain are proposed.