The effects of anesthesia on otoacoustic emissions

We have measured transient-evoked and distortion-product otoacoustic emissions (OAEs) in the chinchilla and compared them in the awake and anesthetized animal (using either ketamine or barbiturate agents). We report a significant increase in OAE amplitudes during anesthesia, particularly using ketamine. These effects are most evident for transient-evoked otoacoustic emissions (TEOAEs) as measured in the non-linear mode. Our data support the hypothesis that tonic activity levels in cochlear efferents may be reduced by anesthetic effects, either directly or indirectly (e.g., by general reductions in descending pathway activity), and that reduced cochlear efferent activity will result in the observed increase of OAE amplitudes.     

Molecular design of biodegradable functional polymers, 3. Biodegradability and functionality of poly[(sodium acrylate)-co-(vinyl alcohol)]

As a design for a biodegradable functional polymer, compositionally homogeneous poly[(sodium acrylate)-co-(vinyl alcohol)] [P(SA-co-VA)], containing varying amounts of vinyl alcohol groups as biodegradable segments were prepared and their biodegradability and builder performance in detergent formulations were analyzed with respect to the successive vinyl alcohol length. It was found that the acrylate copolymers having more than 80 mol-% vinyl alcohol content showed biodegradability. That is, P(SA-co-VA) having a vinyl alcohol chain length of more than about 5–6 is cleaved by PVA-degrading microbes. This indicates that the vinyl alcohol blocks, which act as biodegradable segments, should be incorporated into the polymer chain in such a manner that they are accepted as substrates by the PVA-degrading enzymes.     

Identification of Vibrio parahaemolyticus pandemic group-specific DNA sequence by genomic subtraction

A genomic subtraction between a pandemic Vibrio parahaemolyticus and a nonpandemic strain that seemed to be clonally related was performed. A subtractive DNA fragment was identified to be a part of a 16-kbp insertion sequence which was present in almost all pandemic strains but not in nonpandemic strains tested.     

Cognitive mapping in children: using a bird's-eye view in small- and large-scale spaces

It is hypothesized that a bird's-eye view affects children's thinking on the transition from route to configurational knowledge. Children were asked to make a cognitive map about the region where they live. Then each child was identified whether he had a bird's-eye view or not according to the small-scale space task (i.e., "apples on the table" task) and the large-scale space task (i.e., "a landscape" task). The results of cognitive mapping showed that the children who had a bird's-eye view on the small- and large-scale space tasks produced a number of "node," "path," and "landmark" and also could place the targets better than the children who did not have a bird's-eye view. It is discussed that there is relationship between a bird's-eye view and production of nodes, and that a bird's-eye view could affect children's cognitive mapping on the transition from route to configurational knowledge.     

Clinical significance of measurement of resting energy expenditure in childhood

1. Biliary atresia (BA), as a common disease in Japan, and cystic fibrosis (CF), as an extremely uncommon disease in Japan, were selected to assess the clinical significance of measurement of energy expenditure (EE). 2. Energy expenditure was significantly higher in children with BA than in normal children. 3. Measurement of EE in BA lead to clues to resolving its mechanism by novel assessment of interleukin-6 and leptin. 4. Energy expenditure in children with CF is also higher, but this has been addressed by nutritional intervention with additional calories. 5. Individualization of EE measurement is necessary in the analysis of pathological mechanisms and nutritional management of patients with both common and uncommon diseases.     

Evidence of allosteric conformational changes in the antibody constant region upon antigen binding

We have addressed the question of whether antigen binding induces a conformational change in the heavy chain constant (C(H)) domain of antibodies using staphylococcal protein A or streptococcal protein G as probes, since these proteins are known to bind to IgG domains such as C(H)1 and C(H)2-C(H)3 domains. Biosensor assays on interactions between these proteins and mouse IgG specific to (4-hydroxy-3-nitrophenyl)acetyl (NP) or their enzymatic fragments conducted in the presence or absence of the hapten, NP-epsilon-aminocaproic acid (NP-Cap), showed that the binding of IgG to these proteins was inhibited by the binding of NP-Cap. The results of isothermal titration calorimetry also revealed that the association constant for the interaction of protein A with IgG2b decreased by the addition of NP-Cap. These results suggested that antigen binding induced conformational changes in binding sites for protein G or protein A located at C(H)1 and C(H)2-C(H)3 domains, respectively.     

Noninvasive prenatal diagnosis of chromosomal aneuploidies by isolation and analysis of fetal cells from maternal blood

The isolation and analysis of nucleated fetal cells (NFCs) from maternal blood may represent a new approach to noninvasive prenatal diagnosis. Although promising, these techniques require highly accurate separation of NFCs from nucleated cells of maternal origin; the two major problems limiting these techniques are the relative rarity of fetal cells in maternal blood and the need to establish their fetal origin. We now report a novel procedure that has allowed accurate separation of NFCs from maternal cells. The technique reported involves direct micromanipulator isolation of histochemically identified hemoglobin F‐positive nucleated cells to obtain fetal nucleated red blood cells (FNRBCs) of high yield and purity. Using this technique, followed by cell‐by‐cell multicolor fluorescence in situ hybridization (FISH) analysis of purified FNRBCs, we were able to detect some of the most common human aneuploidies (including Down syndrome, Klinefelter syndrome, and trisomy 13) in 33 pregnant women referred for amniocentesis. The procedure used, which can be completed in <72 hrs, produced complete concordance with the results of amniocentesis. We also confirm findings of prior studies suggesting that the number of FNRBCs in maternal circulation is remarkably higher in abnormal pregnancies than in normal pregnancies, especially in women carrying a fetus with trisomy 21. © 2001 Wiley‐Liss, Inc.     

The absence of DNA polymerase kappa does not affect somatic hypermutation of the mouse immunoglobulin heavy chain gene

During the immune response to T cell-dependent antigen, somatic hypermutation (SHM) is introduced into immunoglobulin (Ig) genes. The variable region is the target for SHM and it is here that DNA lesions are introduced and mutations are generated. It has been suggested that error-prone DNA polymerase(s) may play an important role in this mutagenesis phase. Recently, DNA polymerase kappa (Polkappa), which belongs to the Y-family of DNA polymerases, was identified. Since a hot spot of SHMs (RGYW motif) is also a hot spot of mutations by human Polkappa, this enzyme was suggested to be an SHM instigator. In order to address the question whether Polkappa is involved in SHM, we immunized Polkappa-deficient mice and analyzed the SHM of the Ig heavy chain gene. We found that the SHM frequency and spectrum were indistinguishable between the Polkappa knockout mice and control mice. These results suggested that Polkappa is not essential for this process.     

Stromal reaction in cancer tissue: Pathophysiologic significance of the expression of matrix-degrading enzymes in relation to matrix turnover and immune/inflammatory reactions

Cancers are characterized by invasive growth and distant metastasis. Cancer cells not only destroy the pre-existing extracellular matrix, but cancer invasion per se usually induces new matrix formation by activation of stromal cells; that is, desmoplastic reaction. This process includes both matrix production and degradation; that Is, the remodeling process. The similarity between desmoplastic reactions in cancer stroma and the wound healing process has already been pointed out, and it has been well documented that matrix-degrading processes are actively involved In the wound healing process. A recent study revealed that most matrix-degrading enzymes, generally considered to be one of the main mechanisms of cancer invasion and metastasis, are originated from stromal cells. Based on these preconditions, the present review postulates that the abundant expression of matrix-degrading enzymes by fibroblasts, coupled with the abundant expression of type I procollagen, is involved in the matrix remodeling processes occurring in cancer stroma; that is, the mechanism similar to the wound healing process. Next, macrophages distributed along the invasive margin are known to express matrix-degrading enzymes/factors. Data from past studies of colon carcinoma indicate that the tissue expression of matrix metalloproteinase-9 and urokinase-type plas-mlnogen activator receptor Is inversely associated with simultaneous liver metastasis and infiltrating growth pattern. Previous clinicopathologic data have indicated that immune/Inflammatory cells are one of the factors for a favorable prognosis. This suggests that the expression of matrix-degrading enzymes/factors by these host cells may be involved in host immune/inflammatory reactions, and that the net function of these cells can be defensive towards the host. Data from past studies of colon carcinoma on the expression of the intercellular adhesion molecule-1 suggest that the interaction between macrophages, lymphocytes, and the phenotypes of venules distributed along the Invasive margin, further support the pro-inflammatory milieu there. Therefore, the matrix degradation process in cancer tissue is multifunctional: besides the Involvement in cancer invasion and metastasis, the matrix degradation process is also involved in the tissue remodeling process and in the immune/inflammatory reaction occurring in the stroma.