Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Green tea consumption and gastric cancer in Japanese: a pooled analysis of six cohort studies.

BACKGROUND: Previous experimental studies have suggested many possible anti-cancer mechanisms for green tea, but epidemiological evidence for the effect of green tea consumption on gastric cancer risk is conflicting. OBJECTIVE: To examine the association between green tea consumption and gastric cancer. METHODS: We analysed original data from six cohort studies that measured green tea consumption using validated questionnaires at baseline. Hazard ratios (HRs) in the individual studies were calculated, with adjustment for a common set of variables, and combined using a random-effects model. RESULTS: During 2 285 968 person-years of follow-up for a total of 219 080 subjects, 3577 cases of gastric cancer were identified. Compared with those drinking <1 cup/day, no significant risk reduction for gastric cancer was observed with increased green tea consumption in men, even in stratified analyses by smoking status and subsite. In women, however, a significantly decreased risk was observed for those with consumption of > or =5 cups/day (multivariate-adjusted pooled HR = 0.79, 95% confidence interval (CI) = 0.65 to 0.96). This decrease was also significant for the distal subsite (HR = 0.70, 95% CI = 0.50 to 0.96). In contrast, a lack of association for proximal gastric cancer was consistently seen in both men and women. CONCLUSIONS: Green tea may decrease the risk of distal gastric cancer in women.

Double ventricular response via dual atrioventricular nodal pathways resulting with nonreentrant supraventricular tachycardia and successfully treated with radiofrequency catheter ablation.

We report a patient with a complex nonreentrant supraventricular tachycardia because of double ventricular response resulting from antegrade dual atrioventricular (AV) nodal pathways. We could induce double ventricular response and confirm dual AV nodal pathways by AV simultaneous pacing during basic stimulation proceeding with programmed atrial single extrastimulation. As far as we know, it is the first report about the application of the AV simultaneous basic stimulation to prove the sustained nonreentrant tachycardia because of simultaneous conduction over dual AV nodal pathways. This was also confirmed by absence of the arrhythmia immediately after the elimination of the slow pathway conduction by radiofrequency ablation.

Anti-androgenic activity of Myricae Cortex--isolation of active constituents from bark of Myrica rubra.

The aqueous ethanol extract of Myricae Cortex (bark of Myrica rubra Sieb. et Zucc., Myricaceae) showed in vitro testosterone 5alpha-reductase inhibitory activity and in vivo anti-androgenic activity using growth of flank organ in castrated Syrian hamsters and/or hair regrowth after shaving in testosterone-treated C57Black/6CrSlc mice. Three constituents, myricanone, myricanol, and myricetin were identified as the main active principles.

Study on anti-Oketsu activity of rhubarb II. Anti-allergic effects of stilbene components from Rhei undulati Rhizoma (dried rhizome of Rheum undulatum cultivated in Korea).

Methanol extract (RM-ext) obtained from the dried rhizome of Rheum undulatum was screened for activity in experimental models of type I allergy. RM-ext exhibited the inhibition on 48-h homologous passive cutaneous anaphylaxis (PCA) in rats and an antigen-induced histamine release from rat peritoneal mast cells. Among nine stilbenes isolated from RM-ext, seven inhibited the histamine release. Rhapontigenin (compound 1), piceatannol (2) and piceatannol 3'-beta-D-glycoside (6) with oral administration showed the inhibition on PCA. Compounds 1 and 2 exhibited the inhibitory effect on sheep red blood cell-induced delayed-type hyper sensitivity (SRBC-DTH) of type IV allergic model. These results indicated that the rhizome of Rheum undulatum inhibits the allergic reactions and that these inhibitory effects may be partially attributable to the stilbenes mentioned above.

[A comparison of the effectiveness of transtracheal heating and humidification system in maintaining body temperature during general anesthesia with low flow gases].

We evaluated the effectiveness of transtracheal heating and humidification system in maintaining body temperature during general anesthesia with low flow gases in 12 gastric cancer patients. Patients were divided into two group; Control group A in which a hot-water circulating system was used and group B in which a transtracheal heating and humidification system by ANAMED HUMITUBE was used, during gastric cancer operation. Compared to the hot-water circulating system, the transtracheal heating and humidification system is more effective for maintaining body temperature and humidification after abdominal lavage by warm saline water. But there was no difference between the two groups about awakening from general anesthesia. We concluded that transtracheal heating and humidification system by ANAMED HUMITUBE is effective in maintaining body temperature under general anesthesia with low flow gases.

Role of functional block extension in lesion-related atrial flutter.

BACKGROUND: A line of block in the right atrium (RA) between the venae cavae is necessary to obtain classic atrial flutter (AFL). We tested the hypothesis that the location of that line of block would determine whether the AFL reentrant circuit would be due to single-loop reentry or figure-of-8 reentry. METHODS AND RESULTS: Simultaneous mapping from 392 sites (both atria and the atrial septum) was performed in 13 normal dogs before and after creating a linear lesion on the RA free wall. The lesion was 1 to 1.5 cm anterior and parallel to the crista terminalis (7 dogs) or posterior and close to the crista terminalis region (6 dogs). Sustained AFL (>2 minutes) was then induced. In 4 dogs with an anterior lesion, the AFL reentrant circuit traveled around the lesion (lesion reentry). In 9 dogs (3 with anterior lesions and 6 with posterior lesions), the AFL reentrant circuit included the anterior RA free wall, the atrial septum, and Bachmann's bundle (single-loop reentry). In these 9 dogs, the fixed line of block was extended to the superior and/or inferior vena cava by a functional line of block, thereby preventing lesion reentry. No figure-of-8 reentry was induced. CONCLUSIONS: In this model, the location of a fixed line of block and its functional extension determine the type of AFL reentry. These data provide an explanation for the chronic AFL that occurs in some patients after surgical repair of congenital heart lesions.

Effect of long-term, low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir resistance of herpes simplex virus type 2.

We have examined the susceptibility to acyclovir and frequency of acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions.

Effects of tibolone (Org OD14) treatment for 3 months on ovariectomy-induced osteopenia in 8-month-old rats on a low-calcium diet: preventive testing for 3 months.

Tibolone (Org OD14), (7alpha, 17alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn++ +-3-one, is a synthetic steroid with weak estrogenic, progestational, and androgenic properties. We investigated the prophylactic effects of tibolone on bone loss, bone strength, and plasma and urinary parameters in 8-month-old ovariectomized rats on a low-Ca diet. Oral administration of tibolone (0.03-3 mg/kg/day) was started immediately after ovariectomy (ovx) and continued for 3 months. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Oral administration of tibolone (1 or 3 mg/kg/day) significantly prevented a decrease in BMD and bone ash density (bone ash weight/volume) of the global femur, and BMDs in the femoral distal and proximal regions. Also in the lumbar vertebrae, the ovx-induced reduction in BMD was prevented by tibolone (1 and 3 mg/kg/ day) treatment, resulting in a significantly higher lumbar vertebral (L-2) bone compression strength compared to the ovx control group. Neither ovx alone nor supplemented with tibolone affected the BMD or bending strength of the femoral mid-diaphysial region. Tibolone (0.03-3 mg/kg/day) significantly reduced the ovx-induced increases in serum osteocalcin level. Furthermore, tibolone inhibited an increase in the urinary hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine ratios induced by ovx. Tibolone also reduced body weight gain and serum cholesterol level, as has been reported for estrogen. These findings indicate that tibolone prevents reduction in bone mass associated with osteopenia by reducing increased trabecular bone resorption induced by a combination of ovx and a low-Ca diet.

Genotypes of sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase II gene in substrains of spontaneously hypertensive rats.

OBJECTIVE: To search for a genetic marker of the sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (SERCA) II gene in spontaneously hypertensive rats (SHRs) and to investigate differences in blood pressure and intracellular Ca2+ among some substrains of SHRs and Wistar-Kyoto (WKY) rats related to their SERCA II genotypes. DESIGN AND METHODS: The coding region of the SERCA II gene was sequenced in SHRs. Blood pressure and intracellular Ca2+ concentration ([Ca2+]i) in platelets were measured in substrains of SHRs and WKY rats with different SERCA II genotypes. RESULTS: A point mutation that provided restriction fragment length polymorphisms (RFLPs) by HindIII or Saul was found in the SERCA II gene. The polymerase chain reaction (PCR) products were digested by HindIII in SHR substrains and WKY-Kyoto rats, whereas they were digested by Saul in normotensive strains and SHR-Toho. Among SHR-Kyoto, SHR-Toho, WKY-Kyoto and WKY-Charles River, the substrains with the HindIII-digested SERCA II genotype showed slightly but significantly higher systolic blood pressure and augmented agonist-stimulated [Ca2+]i than those with the Saul-digested genotype. CONCLUSIONS: RFLPs were found in the SERCA II gene. In the substrain analysis of SHRs and WKY rats, higher blood pressure and increased [Ca2+]i were associated with the SERCA II genotype digested by HindIII. The SERCA II gene locus has the potential to contribute to the development of hypertension and abnormal intracellular Ca2+ metabolism in SHRs. These RFLPs in the SERCA II gene should be a useful genetic marker.

[In vitro MIC break point for appropriate clinical use of antibiotic].

In vitro antimicrobial susceptibility tests can play an essential role in clinical management of infectious diseases, and in vitro MIC break point is important in choice of antibiotic. Standardization of method for measuring MIC is necessary, if break points are to be fixed internationally. However, it is difficult to settle on uniform international break points, since standard doses of antibiotics and the preferred routes of administration differ in different parts of the world. With respect to in vitro MIC break points, the NCCLS system is used in the U.S.A., and in Japan, Showa disc system and the NCCLS system are both used. In Europe 6 different systems are utilized (BSAC, DIN, SFM, SIR, NCCLS, and WRG). There is a certain degree of similarity between different concentration values used to define break points in these systems. In general, however, the BSAC and DIN systems recommend lower break points and the NCCLS and SFM systems higher break points. The MIC values of the break points, +3 and +2 categories of Showa 4 category classification system (+3, +2, +, -) used in Japan, are similar to those of the BSAC system. Higher ratio of positive responses to bactericidal antibiotic therapies have been reported when ratios of peak concentrations of drugs in plasma/in vitro MIC are increased, and maximum responses are obtained when the ratio reaches about 8 in cases with aminoglycosides and beta-lactams. In neutropenic compromised patients, drug concentrations with ratios higher than 8 to 10 may be required to treat infections. Drug availabilities are different depending on drugs and sites of infections. Susceptibility patterns to antibiotics are also quite different with different organisms. From the evidence presented above, a multiple (at least 2, low and high) sensitivity MIC break point system appears to be more appropriate than a single sensitivity MIC break point system to cope with various infections. Multiplicity of break points should depend on types of organisms, antibiotic availabilities at sites of infections, and specific factors in patients. Pharmacokinetic data on antibiotics must be more precisely taken into account with respect to the diversity of dosages, and especially effective antibiotic concentrations at sites of infections.

[Morphological pursuit of blood stem cells emerging from aplastic bone marrow of mouse after a single high dose of 5-FU injection].

A single high dose of 5-fluorouracil (5-FU) was administered intravenously in mice to induce the aplastic bone marrow and to seize the morphological characteristics of blood stem cells. Time course observations of histological and cytological changes in bone marrow hematopoiesis and stem cell assay revealed that the day 2 bone marrow contained a number of quiescent blood stem cells. For advanced morphological studies of blood stem cells, the day 2 marrow cells were seeded in methylcellulose culture medium for stem cell assay. Blast cell colonies (BCC) which contained CFU-GEMM (colony-forming unit granulocyte, erythroid, monocyte/macrophage, megakaryocyte) were formed within 2 weeks. BCC-constituting cells (BCC-cell) were lifted and processed for morphological analyses. The BCC-cells were variable in size as well as morphology, and were divided into 3 sub-groups according to their size. Large-sized group (greater than 14 microns) consisted of large blastic cells with a tendency of differentiation into early granulocyte or monocyte/macrophage lineage. Medium-sized group (10-14 microns) consisted of more immature blastic cells which lacked a differentiation. Small-sized group (7-10 microns) consisted of two cell-types. One type (named 'transitional cell' or 'TC cell') had distinctive features as a dark nucleus and a narrow basophilic cytoplasm seemed to be the most immature cell type. The other (named 'lymphoid cell') was morphologically indistinguishable from the small lymphocyte. Blast cell colony-replating experiments disclosed that the proportion of small-sized cells in BCC-cells (about 4%) was equivalent to the incidence of GEMM colonies formed in replated culture (about 2-5%). Furthermore, immunohistochemical staining of wheat germ agglutinin (WGA), anti-Thy-1 antibody and anti-B cell antibody revealed that most of TC cells were positive for WGA suggesting of CFU-GEMM, and negative for anti-B cell antibody. Most of lymphoid cells were positive for anti-B cell antibody, and negative for WGA and anti-Thy-1 antibody, and were estimated to be true B-lymphocytes. Based on these results, it was reasonable to consider that a majority of TC cells were multipotent blood stem cells.

[A new technique to prepare non-reversed autovein graft].

Non-reversed autovein graft was prepared by using a long saphenous vein. Disposable enema-syringe was used for vein graft to be turned inside out easily, and venous valves were resected out completely. After these procedure, a graft was put with syringe again, and turned outside in with same maneurver. Then, a non-reversed autovein graft without valves was prepared. We believe this is an excellent method to prepare non-reversed valveless autovein graft to be used as bypass grafting for cardiovascular surgery.

The postauricular myogenic response in normal children and children with microtia.

The effect of the development of postauricular muscles on the postauricular myogenic response (PAR) was investigated in normal children and children with microtia. There were no differences between the PAR of normal children and that of the intact ear of children with microtia. The PAR obtained from the normal and microtic sides of children with unilateral microtia showed no significant differences as regards waveform, latency, threshold, or amplitude. Our findings suggest that the development of the postauricular muscle does not affect the PAR, and it seems difficult to explain the large individual variations in the PAR by intersubjective differences in muscle development.

[Clinical laboratory approach for determination of effective dose of cefotiam. Observation from disc susceptibility test and MICs].

Reliability of cefotiam disc diffusion susceptibility test was investigated for determining whether the disc results correlate with minimal inhibitory concentration (MIC) or not. The results of Showa disc and Oxoid disc were well correlated. The inhibitory zone size of Showa disc and MIC were also well correlated, indicating reliability of the cefotiam disc test. The disc result, was observed over 84% of clinically isolated S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes, E. coli, K. pneumoniae, P. mirabilis and H. influenzae. Their mean MICs were less than about 1.5 microgram/ml. Such a result should be useful for the determination of drug dose in various clinical conditions in order to obtain the proper drug levels in blood and tissues. The results of antibiotic disc diffusion susceptibility test with various bacteria isolated from clinical materials were compared. Cefotiam revealed a potent antimicrobial activity against Gram-positive cocci, showing a similar potency to that of cephalothin and cefazolin. However, it showed a stronger activity against Gram-negative bacilli than that of cephalothin, cefazolin, cephalexin and cefoxitin, revealing less resistant strains. Cephalosporins developed recently such as cefotaxime, cefoperazone, ceftizoxime, latamoxef etc. show very potent antimicrobial activity against Gram-negative bacilli, but their activity against S. aureus and S. epidermidis is weaker than that of cefotiam, cephalothin, cefazolin etc. Therefore, cefotiam can be considered as one of the drugs of first choice for surgical perioperative prophylaxis and blind therapy.