Allowable level of lifetime cadmium intake calculated from the individuals in the Jinzu River basin of Japan

We investigated a dose-response relationship between renal dysfunction and liftime cadmium intake in individual subjects using logistic regression analysis and calculated the allowable level of lifetime cadmium intake among the inhabitants of the Jinzu River basin. From the participants of 1967 and 1968 health examinations, target subjects in whose hamlet the cadmium concentration in rice was known and whose history of residence was also known were selected. Cadmium concentrations in rice from data analyzed by the Toyama Prefecture from 1971 to 1976 were used. The urinary examination was done by semiquantitative determination of protein and glucose. All odds ratios for lifetime cadmium intake obtained from logistic regression analysis were more than 1 in both males and females who had resided in their current hamlet since birth with and without subjects who moved from nonpolluted areas and with or without the control group. The allowable levels of lifetime cadmium intake were calculated by substituting the abnormality rates of urinary findings of the controls 40, 50, 60, and 70 yr old into the logistic regression formula. The allowable levels of lifetime cadmium intake were less than 1.58 g for both sexes and each age group using proteinuria with glucosuria measurements.     

Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice

We recently reported that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against a heart-specific, 30-kDa protein. In this study, we purified the 30-kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal antibodies to cTnI induced dilatation and dysfunction of hearts in wild-type mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and augmented the voltage-dependent L-type Ca2+ current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes.     

Beta 3-adrenergic receptor is involved in feeding regulation in chicks

We examined whether the brain beta 3-adrenergic receptor (B3-AR) is involved in the feeding regulation of chicks. Intracerebroventricular (ICV) injection of BRL37344, a B3-AR agonist, reduced food intake of chicks under ad libitum, but not fasting, feeding conditions. The ICV injection of BRL37344 did not affect chick posture or locomotion activity suggesting that BRL37344 inhibited feeding without induction of sleep-like behavior as caused by norepinephrine. Furthermore, the rectal temperature increased following the ICV injection of BRL37344. Intraperitoneal administration of BRL37344 did not reduce food intake under ad libitum feeding condition. The present study demonstrated that the brain B3-AR is involved in the inhibition of feeding in chicks. We also suggested that activation of the brain affects the energy metabolism in chicks.     

The crucial role of caspase-9 in the disease progression of a transgenic ALS mouse model

Mutant copper/zinc superoxide dismutase (SOD1)-overexpressing transgenic mice, a mouse model for familial amyotrophic lateral sclerosis (ALS), provides an excellent resource for developing novel therapies for ALS. Several observations suggest that mitochondria-dependent apoptotic signaling, including caspase-9 activation, may play an important role in mutant SOD1-related neurodegeneration. To elucidate the role of caspase-9 in ALS, we examined the effects of an inhibitor of X chromosome-linked inhibitor of apoptosis (XIAP), a mammalian inhibitor of caspase-3, -7 and -9, and p35, a baculoviral broad caspase inhibitor that does not inhibit caspase-9. When expressed in spinal motor neurons of mutant SOD1 mice using transgenic techniques, XIAP attenuated disease progression without delaying onset. In contrast, p35 delayed onset without slowing disease progression. Moreover, caspase-9 was activated in spinal motor neurons of human ALS subjects. These data strongly suggest that caspase-9 plays a crucial role in disease progression of ALS and constitutes a promising therapeutic target.     

Molecular structure of bacterial endotoxin (Escherichia coli Re lipopolysaccharide): implications for formation of a novel heterogeneous lattice structure

Analyses of crystals of Escherichia coli Re lipopolysaccharide (LPS) formed after storage in 1% triethylamine indicate that the LPS molecules are assembled to form a monolayered structure consisting of a novel heterogeneous lattice structure, the greater part of which is occupied by one kind of lattice (lattice I), corresponding to the acyl chain portion of lipid A, and the remainder is occupied by the other kind of lattice (lattice II), corresponding to the 3-deoxy-Dmanno-octulosonic acid (dOclA) dimer and the N-acetylglucosamine disaccharide of lipid A. X-ray diffraction reveals that the type of cell is monoclinic (a = 5.53 A, b = 27.2 A, c = 6.47 A, alpha = 90 degrees, beta = 125.8 degrees, gamma = 90 degrees ). Atomic force microscopy shows that crystals consist of multiple layers; the thickness of a layer corresponds to the b-axis value, and two types of surface topographies are visualized. One, regarded as the view onto the acyl chain ends, is two-dimensional arrays of oval bodies that constitute the lattice, with the lattice constants corresponding to the a- and c-axes and the angle of beta (lattice I). The other, regarded as the view onto the dOclA dimers, is two-dimensional arrays of dromedary-back-like bodies that constitute the lattice with axes of 9.0 and 10.7 A and the angle of 65 degrees formed by both axes (lattice II). Based on these results, we present the molecular model of E. coli Re LPS.     

Correlated gene expression between beta-1,4-galactosyltransferase V and N-acetylglucosaminyltransferase V in human cancer cell lines

Since our previous study showed that the gene expression level of beta-1,4-galactosyltransferase (beta-1,4-GalT) V is only increased in mouse NIH3T3 transformant and that beta-1,4-GalT V preferentially galactosylates the GlcNAcbeta1 --> 6Man branch of oligosaccharides [Shirane et al. (1999) Biochem. Biophys. Res. Commun. 265, 434-438], whether its gene expression is correlated with malignant transformation was investigated. Northern blot analysis of beta-1, 4-GalTs I, II, III, IV, V, and VI and N-acetylglucosaminyltransferase (GlcNAcT)V in human cancer cell lines showed that the gene expression levels of beta-1,4-GalT V but not other beta-1,4-GalTs are strongly correlated with those of GlcNAcT V whose activity was shown to increase by malignant transformation. These results indicate that beta-1,4-GalT V is involved in the galactosylation of highly branched oligosaccharides characteristic of malignantly transformed cells.     

Rapid and simple detection of PCR product DNA: a comparison between Southern hybridization and fluorescence polarization analysis

The essential aim of this study was to compare two different methods, Southern hybridization and fluorescence polarization (FP) assay. They both detect specific hybridization and were examined using common asymmetric PCR products and probes. FP assay clearly showed the hybridization of probe DNAs with the asymmetric PCR products of their target genes. Southern blot patterns presented excellent consistency with the results of FP assay. In both methods, two types of Shiga toxin (vero toxin) genes held in enterohaemorrhagic Escherichia coli (EHEC) were used as target genes. For detection of the two genes, stx1 and stx2, two respective DNA probes were synthesized. Both in FP assay and in Southern hybridization, the probe for stx1 hybridized only with the product of stx1 and vice versa. The results of the DNA detection using different methods were completely in agreement. Moreover, FP assay makes it possible to detect the hybridization rapidly. In our high NaCl concentration condition, hybridization between the probes and the asymmetric PCR products could be monitored within about 15min.     

Antinociceptive substances from Incarvillea delavayi

Antinociceptive activities of an Incarvillea delavayi extract, as well as its constituents, 8-epideoxyloganic acid and delavayine A, were evaluated in the acetic acid induced writhing test in mice. An oral administration of the delavayi extract weakly decreased the number of writhings and stretchings in this test, in a dose-dependent manner. Furthermore, orally administered 8-epideoxyloganic acid showed weak antinociceptive activity, whereas administration by subcutaneous injection did not. However, subcutaneous injection of delavayine A, a novel monoterpene alkaloid, showed a more significant level of antinociceptive activity.     

Possible involvement of PPARγ in the regulation of basal channel opening of P2X7 receptor in cultured mouse astrocytes

AimsRecently, we demonstrated that cultured mouse astrocytes exhibited basal channel opening of P2X7 receptor (P2X7R) in the absence of any exogenous ligand, but the regulatory mechanism involved was not elucidated. Since our preliminary experiments suggested possible involvement of peroxisome proliferator-activated receptor (PPAR) γ in the regulation, we examined whether PPARγ regulated P2X7R basal channel opening in mouse astrocytes.Main methodsP2X7R channel opening was assessed as to the uptake of a marker dye, YO-PRO-1^® (YP), in the presence or absence of agonists and antagonists for PPARγ under a fluorescence microscope. Expression of PPARγ was evaluated by Western blotting and immunocytochemistry.Key findingsNSAIDs such as flufenamic acid (FFA) and indomethacin, which are a cyclooxygenase inhibitor and a PPARγ agonist, showed enhancing and inhibiting effects on YP uptake at low and high concentrations, respectively, and the enhanced uptake was abolished by periodate-oxidized ATP (oxATP), a selective P2X7R antagonist. The PPARγ agonists 15-deoxy-Δ^12,14-prostaglandin J₂ and ciglitazone decreased the basal and FFA-enhanced YP uptake, while the antagonist GW9662 increased YP uptake, this effect being blocked by the agonists and also by oxATP. PPARγ was distributed in the nucleus and cytosolic/membrane fraction of cultured mouse astrocytes.SignificanceThese findings indicate that basal channel opening of P2X7R in mouse astrocytes is at least in part regulated by PPARγ.     

The Investigation of Posttraumatic Pseudoaneurysms in Patients Treated with Nonoperative Management for Blunt Abdominal Solid Organ Injuries

Background

Posttraumatic pseudoaneurysms (PAs) have been recognized as the cause of delayed hemorrhage complicated with nonoperative management (NOM), although the need for intervention in patients with small-sized PAs and the relationship between the occurrence of PAs and bed-rest has been also unclear.

Objectives

The purpose of this study was to investigate the clinical history of small-sized PAs (less than 10 mm in diameter) which occurred in abdominal solid organs, and to analyze the relationship between the occurrence of PAs and early mobilization from bed.

Methods

Sixty-two patients who were successfully managed with NOM were investigated. Mobilization within three days post-injury was defined as “early mobilization” and bed-rest lasting over three days was defined as “late mobilization.” A comparison of the clinical factors, including the duration of bed-rest between patients with and without PAs detected by follow-up CT was performed. Furthermore, a multiple logistic regression model analysis on the occurrence of PAs was performed.

Results

PAs were detected in 7 of the 62 patients. The One patient with PAs measuring larger than 10 mm received trans-arterial embolization, and the remaining six patients with PAs smaller than 10 mm were managed conservatively. Consequently, no delayed hemorrhage occurred, and the PAs spontaneously disappeared in all of the six patients managed without intervention. The multiple regression model analysis revealed that early mobilization was not a significant factor predicting new-onset PAs.

Conclusions

Small PAs can be expected to disappear spontaneously. Moreover, early mobilization is not a significant risk factor for the occurrence of PAs.