Diagnosing endometrial carcinoma with cervical involvement by cervical cytology

OBJECTIVE: To assess the relationship of a cervical cytologic diagnosis based on number, size and degeneration of malignant clusters and necrotic background to cervical involvement of endometrial carcinoma. STUDY DESIGN: Cervical smears of 53 women with endometrial carcinoma were evaluated for cervical involvement. The cytologic diagnosis was compared with actual involvement, and accuracy was calculated. Retrospectively, cytologic features, including number, size and degeneration of malignant clusters and necrotic background, were analyzed in involved and noninvolved cases. RESULTS: Cervical involvement was confirmed in 15 patients (28.3%). The number and size of malignant clusters in the involved cases were significantly larger than those in the noninvolved cases (P < .001 and < .01, respectively). The proportion of degenerated malignant cells and necrotic background in involved cases were significantly higher than those in noninvolved cases (P < .05). Cytologic diagnosis had a sensitivity and specificity of 62.5% and 86.8%, respectively. CONCLUSION: Cervical smears of involved cases revealed a large number and large size of malignant clusters. These findings support cytologic diagnosis based on number, size and degeneration of malignant cells and necrotic background. Cervical cytology is useful to exclude cervical involvement because of its high specificity and can help detect cervical involvement because of its moderately high sensitivity.     

Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but not by MK-801 (NMDA receptor antagonist). ERalpha agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ERbeta agonist DPN did not affect the density of thorns. Note that a 1nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ERalpha was performed using purified RC-19 antibody. The localization of ERalpha (67kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ERalpha and MAP kinase.     

Regulation of homologous integration in yeast by the DNA repair proteins Ku70 and RecQ

The product of the BLM gene, which is mutated in Bloom syndrome in humans, and the Saccharomyces cerevisiae protein Sgs1 are both homologous to the Escherichia coli DNA helicase RecQ, and have been shown to be involved in the regulation of homologous recombination. Mutations in these genes result in genome instability because they increase the incidence of deletions and translocations. We present evidence for a genetic interaction between SGS1 and YKU70, which encodes the S. cerevisiae homologue of the human DNA helicase Ku70. In a yku70 mutant background, sgs1 mutations increased sensitivity to DNA breakage induced either by treatment with camptothecin or by the expression of the restriction enzyme EcoRI. The yku70 mutation caused a fourfold increase in the rate of double-strand break (DSB)-induced target integration as that seen in the sgs1 mutant. The combination of yku70 and sgs1 mutations additively increased the rate of the targeted integration, and this effect was completely suppressed by deletion of RAD51. Interestingly, an extra copy of YKU70 partially suppressed the increase in targeted integration seen in the sgs1 single mutant. These results suggest that Yku70 modulates the repair of DSBs associated with homologous recombination in a different way from Sgs1, and that the inactivation of RecQ and Ku70 homologues may enhance the frequency of gene targeting in higher eukaryotes.     

Interaction of gymnemic acid with cyclodextrins analyzed by isothermal titration calorimetry, NMR and dynamic light scattering

The physiological phenomenon that the antisweet taste effect of gymnemic acid (GA) is diminished by application of gamma-cyclodextrin (gamma-CD) to the mouth was evaluated at the molecular level using isothermal titration calorimetry, NMR and dynamic light scattering. These analyses showed that GA specifically binds to gamma-CD. Thermodynamic analysis using isothermal titration calorimetry revealed that the association constant of GA and gamma-CD is 10(5)-10(6) m(-1) with favorable enthalpy and entropy changes. The heat capacity change was negative and large, despite the change in accessible surface area upon binding being small. These thermodynamics indicate that the binding is dominated by hydrophobic interactions, which is in agreement with inclusion complex formation of gamma-CD. In addition, NMR measurements showed that in solution the spectra of GA are broad and sharpened by the addition of gamma-CD, indicating that unbound GA is in a water-soluble aggregate that is dispersed when it forms a complex with gamma-CD. Dynamic light scattering showed that the average diameter of unbound GA is > 30 nm and that of GA and gamma-CD complex is 2.2 nm, similar to unbound gamma-CD, supporting the aggregate property of GA and the inclusion complexation of GA by gamma-CD.     

Kinin receptors in cultured rat microglia

Kinins are produced and act at the site of injury and inflammation in various tissues. They are likely to initiate a particular cascade of inflammatory events, which evokes physiological and pathophysiological responses including an increase in blood flow and plasma leakage. In the central nervous system (CNS), kinins are potent stimulators of the production and release of pro-inflammatory mediators represented by prostanoids and cytotoxins. They are known to induce neural tissue damage. Many of the cytotoxins such as cytokines and free radicals and prostanoids are released from glial cells. Among glial cells, astrocytes and oligodendrocytes are known to possess bradykinin (BK) B(2) receptors that phosphoinositide (PI) turnover and raise intracellular Ca(2+) concentration. The presence of bradykinin receptors in microglia has been of great significance. We recently showed that rat primary microglia express kinin receptors. In resting microglia, B(2) receptors but not B(1) receptors are expressed. When the microglia are activated by bradykinin, B(1) receptors are up-regulated, while B(2) receptors are down-regulated. As observed in other glial cells, electrophysiological measurements suggest that B(2) receptors in phosphoinositide turnover and intracellular Ca(2+) concentration in microglia. Release of cytotoxins is likely consequent upon the activation of BK receptors. Our study provides the first evidence that microglia express functional kinin receptors and suggests that microglia play an important role in CNS inflammatory responses.     

Combining microarrays and biological knowledge for estimating gene networks via bayesian networks

We propose a statistical method for estimating a gene network based on Bayesian networks from microarray gene expression data together with biological knowledge including protein-protein interactions, protein-DNA interactions, binding site information, existing literature and so on. Microarray data do not contain enough information for constructing gene networks accurately in many cases. Our method adds biological knowledge to the estimation method of gene networks under a Bayesian statistical framework, and also controls the trade-off between microarray information and biological knowledge automatically. We conduct Monte Carlo simulations to show the effectiveness of the proposed method. We analyze Saccharomyces cerevisiae gene expression data as an application.     

Autolysis of Porphyromonas gingivalis is accompanied by an increase in several periodontal pathogenic factors in the supernatant

Porphyromonas gingivalis autolyzes in the culture media. To examine in more detail the molecular components of the autolysate, two-dimensional gel electrophoresis was performed. Many protein spots varied both in number and volume. One of these spots included Arg-gingipain (Rgp) as determined by N-terminal amino acid sequencing. Corresponding to the increase in spot volume, Rgp activity also increased during autolysis. The results of this study suggested that Rgp and other proteins in the P. gingivalis autolysate may be involved with the prolongation of periodontal disease, even after the death of P. gingivalis cells.