A novel scale including strabismus and 'cuspidal ear' for distinguishing schizophrenia patients from controls using minor physical anomalies

The present study explored minor physical anomaly items relevant to schizophrenia in order to establish a scale that can distinguish schizophrenia from controls using newly identified items along with items from the refined Waldrop scale. Seven items were significantly more frequent among schizophrenia patients (N=218) than controls (N=226). Among these seven items, two novel features, strabismus and 'cuspidal ear' showed markedly different prevalence rates between schizophrenia and control groups. A six-item scale, including the newly identified strabismus and cuspidal ear, was selected for most accurately discriminating patients with schizophrenia from controls. This scale correctly classified 59.6% of patients and 78.9% of control subjects. This new scale is procedurally more exacting and quantitative, and more relevant to schizophrenia than the original Waldrop scale. The validity of this scale should be sound since it was tested on a larger number of cohorts than used in previous research. Our scale can be used as a biomarker for predicting risk for future development of schizophrenia. The scale may also facilitate the identification of schizophrenia susceptibility genetic/environmental factors by stratifying etiologically heterogeneous patients according to physical abnormalities.     

Volume of left amygdala subregion predicted temperamental trait of harm avoidance in female young subjects. A voxel-based morphometry study

We investigated the relationship between temperamental predisposition and brain structure by using a standard questionnaire and high-resolution T1-weighted magnetic resonance image (MRI) in normal young volunteers. Fifty-six subjects completed the Japanese version of the Temperament and Character Inventory (TCI, 125 items) and underwent an MRI acquisition of the brain. The gray matter (GM) was extracted from the whole brain image of the subjects and normalized to the standard brain template using statistical parametric mapping and the optimized voxel-based morphometry (VBM) method. When the score on the harm avoidance (HA) subscale was used as a dependent variable, the multiple regression analysis revealed that the HA score positively correlated with the volume of the part of left amygdala. The region-of-interest analysis showed that the correlation was significant in the female subjects but not in the male subjects. The correlation was significant even after the effects of age, depression score, and total GM volume were taken into account. The differential correlation between the sexes may be caused by differences in hormonal condition and the vulnerability of women to socio-psychological stress. In addition, the novelty seeking (NS) score positively correlated with the GM of the left middle frontal gyrus. The volume of the tail of the right caudate nucleus positively correlated with the reward dependence (RD) score. With regard to the NS and RD scores, no significant sex difference was observed in the correlation. These results indicate that the temperamental traits measured using the questionnaire may have a morphological basis in the human brain.     

Incidence of hepatocellular carcinoma in HCV-infected patients with normal alanine aminotransferase levels categorized by Japanese treatment guidelines

Background

This study was conducted to evaluate Japanese treatment guidelines for patients with chronic hepatitis C virus (HCV) infection and normal alanine aminotransferase (N-ALT) levels from the viewpoint of the incidence of hepatocellular carcinoma (HCC).

Methods

Four groups of patients with chronic HCV infection treated with pegylated interferon (Peg-IFN) plus ribavirin, and classified according to the N-ALT guidelines, were examined for HCC incidence: group A (n = 353), ALT ≤30 IU/L and platelet (PLT) ≥15 × 10⁴/mm³; group B (n = 123), ALT ≤30 IU/L and PLT <15 × 10⁴/mm³; group C (n = 233), 30 < ALT ≤ 40 IU/L and PLT ≥15 × 10⁴/mm³; and group D (n = 100), 30 < ALT ≤ 40 IU/L and PLT <15 × 10⁴/mm³. The mean observation period was 36.2 ± 16.5 months

Results

In groups A and C, the HCC incidence was low even in patients with non-response (NR) (cumulative rates at 3 years, 0.0 and 2.9 %, respectively). In groups B and D, 14.5 and 5.3 % of NR patients had developed HCC at 3 years, but none of the patients with sustained virologic response (SVR) or relapse had developed HCC. In group B, no patients with mild fibrosis developed HCC irrespective of the antiviral effect of the treatment. Among patients with PLT <15 × 10⁴/mm³ (group B plus group D), the HCC incidence was significantly lower in patients with SVR and relapse than in NR patients (p < 0.001, p = 0.021, respectively).

Conclusion

These results suggest that N-ALT patients with PLT <15 × 10⁴/mm³ could be candidates for early antiviral therapy.     

The (R)-omeprazole hydroxylation index reflects CYP2C19 activity in healthy Japanese volunteers

Purpose

Omeprazole has (R)- and (S)-enantiomers, which exhibit different pharmacokinetics (PK) among patients with cytochrome P450 (CYP) 2C19 genotype groups. The aim of this study was to investigate whether the 1-point, 4-h postdose (R)-omeprazole hydroxylation index (HI) of racemic omeprazole reflects the three CYP2C19 genotype groups in Japanese individuals.

Methods

Ninety healthy Japanese individuals were enrolled and classified into the three different CYP2C19 genotype groups: homozygous extensive metabolizers (hmEMs; n?=?34), heterozygous EMs (htEMs; n?=?44), and poor metabolizers (PMs; n?=?12). Blood samples were drawn 4 h after the intake of an oral dose of omeprazole 40 mg, and plasma levels of omeprazole and its metabolites were analyzed by high-performance liquid chromatography (HPLC) using a chiral column.

Results

Mean plasma concentrations of (R)- and (S)-omeprazole in PMs were significantly higher than those in hmEMs and htEMs, and similar results were obtained in the case of omeprazole sulfone. Additionally, there was a significant difference in plasma concentrations of (R)-5-hydroxyomeprazole among CYP2C19 genotype groups, whereas no significant differences were observed in that of (S)-5-hydroxyomeprazole. Similarly, (R)-omeprazole HI in hmEMs, htEMs, and PMs were 5.6, 3.1, and 0.3, respectively, which were significantly different, but no significant difference was present in the (S)-omeprazole HI.

Conclusion

Our findings demonstrate that (R)-omeprazole HI correlated better with CYP2C19 genotype groups than racemic-omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment.     

Asparosides A and B,two new steroidal saponins from Asparagus meioclados

Asparosides A ( 1 ) and B ( 2 ), two new saponins, were isolated from the roots of Asparagus meioclados . On the basis of chemical and spectroscopic evidence, their structures were elucidated as 23- O - f -arabinopyranosyl-(5 g ,25s)-spirostan-3 g ,23 f -diol-3- O -[ g - d -xylopyranosyl(1 M 4)]- g - d -glucopyranoside and 26- O - g -glucopyranosyl-5 g -furost-20(22)-ene-3 g ,26-diol-3- O -[ g - d -xylopyranosyl(1 M 4)]- g - d -glucopyranoside, respectively.     

DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells

Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis.     

Biomechanical analysis for stress fractures of the anterior middle third of the tibia in athletes: nonlinear analysis using a three-dimensional finite element method

We evaluated stresses in the anterior middle third of the tibia that have been reported to predict a poor prognosis for tibial stress fractures compared to other predominant sites (posteromedial regions of the distal third and proximal third). The effect of two different loads (bending-compression load and torsional load) on three sites was investigated using a three-dimensional finite element method. The model was constructed using the tibia, fibula, proximal tibiofibular joint, interosseous membrane, and tibiofibular ligament based on computed tomography scans obtained at 4-mm intervals of the lower leg of a 20-year-old woman who exhibited no abnormal findings on roentgenograms. First, a normal model was constructed using normal material properties, and then the model was modified to produce fracture models by varying the mechanical properties of each predominant site and expanding the area in three gradual phases on the assumption that the fracture advanced in three phases. Each model was tested against the same two loads, and stresses at the nodal points on the border of the fracture area and normal area were compared in each cross section to determine the effect of the load on fracture advancement. In response to torsional load, both the normal model and fracture models tended to show higher values for the posteromedial distal third than the anterior middle third. By examining the bending-compression load it could be seen that the mean peak value significantly decreased between the first and second phases in fracture models of the anterior middle third. This finding was inconsistent with our previous belief that the bending-compression load would have more serious consequences than the torsional load. In contrast, when the area of fracture was expanded into the third phase, maximum values were significantly higher than during the second phase. No similar finding was observed for the posteromedial distal third, suggesting that the anterior middle third may have the same stable biomechanical conditions as the posteromedial distal third at an earlier stage and thus have little influence on fractures. When the fracture is more advanced, however, the conditions change suddenly, and a bending-compression load may adversely affect the mechanical conditions in this area and thereby cause complete fracture.     

Effects of liquid nitrogen treatment on the proliferation of osteosarcoma and the biomechanical properties of normal bone

 To overcome problems of autografts for reconstruction in the presence of malignant bone and soft tissue tumors, we devised a method for treating autografts that utilizes the hypothermic effect of liquid nitrogen. We measured temperature changes inside the bone at each condition and established a one-cycle liquid nitrogen protocol that included 20 min in liquid nitrogen, 15 min in room air, and 15 min in physiological saline. The proliferation potential of the tumor cells treated with the liquid nitrogen method was examined by means of bromodeoxyuridine (BrdU) immunostaining. Tumor proliferation potential in vivo was examined in nude mice. Based on the results we concluded that the tumor cells died out as a result of the liquid nitrogen method. Regarding compression strength there was no significant difference between intact bone and liquid nitrogen-treated bone, whereas the strength of the autoclaved bone was decreased. Scanning electron microscopic examination of the fracture surface of the autoclaved bone after the compression test showed an irregular, uneven surface, whereas that of the liquid nitrogen-treated bone was smooth and fine-grained. This might be one of the reasons for the discrepancy in compression strength. Received: June 3, 2002 / Accepted: December 2, 2002 RID="*" ID="*" Offprint requests to: H. Tsuchiya