The effect of TRH on 5-HT1 receptors in the rat brain was investigated. A crude membrane preparation was incubated at 37 degrees C for 15 min with or without TRH prior to [3H]5-HT binding assay. TRH at 100 nM increased the number of 5-HT1 receptors significantly (approximately 20%) in the limbic forebrain and the hippocampus without altering their affinity. As this concentration of TRH is close to its dissociation constant (2 nM and 51 nM in the limbic forebrain, 11 nM in the hippocampus), this effect is probably of physiological relevance. This finding seems to support a pharmacological finding of others that the anti-convulsion effect of TRH may be related to increased serotonergic transmission.

Amygdala↗

PubMedDate not supplied

Multilocational hepatocyte transplantation for treatment of congenital ascorbic acid deficiency rats.

We attempted multilocational hepatocyte transplantation (HCTx) including hepatocyte-bearing polyurethane foam (PUF) to treat congenitally ascorbic acid (AsA) biosynthetic enzyme-deficient (ODS-od/od) rats. Hepatocytes isolated from the liver of congeneic rats were transplanted into the portal vein (Pv), spleen (Sp), omentum (Om), and mesentery (Ms). Hepatocyte-bearing PUF was transplanted into the Om and Ms. Experimental groups were divided into four groups (group I; Pv + Sp, group II; Pv + Sp + Om + Ms, group III; Pv + Sp + hepatocyte-bearing PUF, group IV; control). The average serum AsA level of the surviving rats in group II and III was significantly higher than that in group I 3 mo after HCTx. Histological examination showed small foci of surviving hepatocytes in the Om and Ms tissues and in the connective tissue in the PUF. ODS-od/od rats survived for a long time by multilocational HCTx.

Animals↗

PubMedDate not supplied

Representation of molecular configurations by CAST coding method.

A configurational CAST (CAnonical representation of STereochemistry) coding method, which represents relative and absolute configuration, is described. The configurational CAST codes are constructed by canonical rotation of the dihedral angles of the input structure before the CAST codes are assigned. Using the configurational CAST, configurational differences can be distinguished independently of conformational differences. Representation of enantiomers is also achieved by a mirror image conversion method. The CAST representation shows the distinctive characteristics of several diastereomers and conformers that were examined. The method clearly represents the differences in configurations. Applications to organic molecules having complex stereochemistry are also demonstrated.

Journal Article↗

PubMedDate not supplied

Quantitative structure--activity relationships of the synthetic substrates for elastase enzyme using nonlinear partial least squares regression.

Eighty-nine synthetic substrates for elastase enzyme and its activities (log 1/Km, log kcat, and log Kcat/Km) are treated using partial least squares (PLS) and quadratic partial least squares (QPLS). Chemical features of synthetic substrates are described using principal properties (PPs). By using the QPLS method, we obtain the nonlinear model equations for three properties (log 1/Km, log kcat, and log kcat/km) with the correlation coefficient 0.736, 0.918, and 0.868, respectively. Also, the predictive correlation coefficients for these model equations are 0.640, 0.865, and 0.793, respectively. By this study, it becomes clear that the z2 value of the amino acid residue on position A and the size of the side chain for amino acid residues on position B are related to the properties of the synthetic substrates.

Amino Acid Sequence↗

PubMedDate not supplied

GA strategy for variable selection in QSAR studies: GA-based PLS analysis of calcium channel antagonists.

The GAPLS (GA based PLS) program has been developed for variable selection in QSAR studies. The modified GA was employed to obtain a PLS model with high internal predictivity using a small number of variables. In order to show the performance of GAPLS for variable selection, the program was applied to the inhibitor activity of calcium channel antagonists. As a result, variables largely contributing to the inhibitory activity could be selected, and the structural requirements for the inhibitory activity could be estimated in an effective manner.

Algorithms↗

PubMedDate not supplied

Nonlinear partial least squares modeling of phenyl alkylamines with the monoamine oxidase inhibitory activities.

The nonlinear partial least squares (PLS) method is a nonlinear version of PLS. In this approach, a quadratic inner relation is used instead of the linear inner relation in PLS. Since the quadratic inner relation can be extended to a general form, it is said that the nonlinear PLS method has a high potential for nonlinear modelling. However, few applications of the method have been appeared in quantitative structure--activity relationships (QSAR) studies, because the mathematical descriptions underlying the algorithm were not so clear. In this paper, we have carried out the QSAR analysis of four monoamine oxidase (MAO) inhibitory activities using the nonlinear PLS method. The in vitro and in vivo MAO inhibitory activities were analyzed separately. From the PLS loadings, the structural requirements could be estimated and the utility of the nonlinear PLS method was demonstrated.

Amines↗

PubMedDate not supplied

GA strategy for variable selection in QSAR studies: application of GA-based region selection to a 3D-QSAR study of acetylcholinesterase inhibitors.

Comparative molecular field analysis (CoMFA) with partial least squares (PLS) is one of the most frequently used tools in three-dimensional quantitative structure-activity relationships (3D-QSAR) studies. Although many successful CoMFA applications have proved the value of this approach, there are some problems in its proper application. Especially, the inability of PLS to handle the low signal-to-noise ratio (sample-to-variable ratio) has attracted much attention from QSAR researchers as an exciting research target, and several variable selection methods have been proposed. More recently, we have developed a novel variable selection method for CoMFA modeling (GARGS: genetic algorithm-based region selection), and its utility has been demonstrated in the previous paper (Kimura, T., et al. J. Chem. Inf. Comput. Sci. 1998, 38, 276-282). The purpose of this study is to evaluate whether GARGS can pinpoint known molecular interactions in 3D space. We have used a published set of acetylcholinesterase (AChE) inhibitors as a test example. By applying GARGS to a data set of AChE inhibitors, several improved models with high internal prediction and low number of field variables were obtained. External validation was performed to select a final model among them. The coefficient contour maps of the final GARGS model were compared with the properties of the active site in AChE and the consistency between them was evaluated.

Acetylcholinesterase↗

PubMedDate not supplied

Modulation of immunologic reactions between cultured porcine hepatocytes and human sera.

In the clinical application of a hybrid artificial liver system using porcine hepatocytes, some immunologic reactions occur between human serum and porcine hepatocytes. In this study, we investigated the immunologic mechanisms of the cytotoxic reactions, and we tried to inactivate the human serum cytotoxicity by heating the serum or the addition of nafamostat mesilate (NM). Immunologic reaction between human serum and porcine hepatocytes by evaluating the immunochemical response against human IgM, IgG, and C3 was investigated. The immunochemical analysis of inactivation by heated human serum (56 degrees C, 30 min) and adding NM were performed. The evaluation of serum cytotoxicity was as follows: when porcine hepatocytes were cultured with heating the human serum or the addition of NM, the survival ratio was observed. Immunochemical reactions against human C3 were all positive, but positive reaction against human IgM occurred in only one case (5%); those against human IgG were all negative. Both heating the serum and adding NM inhibited the immunochemical reaction of human C3. The inhibition of human C3 with NM was dependent on that concentration. Both heating of the serum and adding NM to the medium decreased damage of porcine hepatocytes. An immunologic reaction between human serum and porcine hepatocytes in a porcine bioartificial liver clearly occurred, and this reaction was controlled by heating the serum and adding NM. We believe that NM is useful in the clinical application of our hybrid artificial liver system.

Adult↗

PubMedDate not supplied

A case of a solitary metastatic diaphragmatic tumor--relation to the peritoneal stomata of the diaphragm.

We herein describe a metastatic diaphragmatic tumor, an entity that has rarely been reported radiologically. The primary lesion was advanced colon cancer, and the root of the metastasis was thought to be the peritoneal stoma(ta) of the diaphragm, which has previously been shown to absorb both intraperitoneal fluid and small particles.

Adenocarcinoma↗