MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents

Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo-cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1-related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labelling and anti-MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell-adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth-promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.     

Reliability,validity and standardization of the Japanese version of the Social Adjustment Scale-Self Report

The purpose of the present paper was to examine the reliability and validity of the Japanese version of the Social Adjustment Scale-Self Report (SAS-SR) and to present its normative data. The SAS-SR was administered to a random sample of all the employees of a large general hospital, together with the General Health Questionnaire (n = 363). It was also administered to a representative subset of first-visit patients at 33 psychiatric hospitals and clinics from all over Japan, along with the semistructured psychiatric interview to ascertain the patients' diagnoses (n = 1581). For the internal consistency reliability of the subscales and the overall scale of the SAS-SR, Cronbach's alpha was between 0.61 and 0.73. The Pearson product-moment correlations between the subscale and overall scale scores with the GHQ score were mostly >0.3. The scores were statistically significantly and substantively different between the normal sample and the patient samples, and were also meaningful, differentiating between various diagnostic subgroups. The reference ranges of the SAS-SR scores for mentally healthy subjects were calculated as 95% prediction intervals; for example, 1.22-2.22 for the overall score. The Japanese version of the SAS-SR has good reliability and satisfactory validity. The present study provided reference ranges for its scores in order to increase their interpretability. With its ease of administration and its rich subscales, the scale promises to offer a psychometrically sound measure with which to assess social adjustment in people with various psychiatric disorders.     

Microglial ecto-Ca(2+)-ATPase activity in a rat model of focal homologous blood clot embolic cerebral ischemia: an enzyme histochemical study

Post-ischemic changes in ecto-Ca(2+)-ATPase activity in microglia and the infarcted tissue were studied in a rat model of focal embolic cerebral ischemia using an enzyme histochemical method. Ecto-Ca(2+)-ATPase activity was observed in whole brains in non-operated and sham-operated control animals. In addition, this enzyme activity was determined to be localized in ramified microglia. At 30 min after ischemia, non-microglial ecto-Ca(2+)-ATPase activity in the infarcted tissue slightly decreased and continued to decrease thereafter. The ecto-Ca(2+)-ATPase activity in microglia did not appear changed at this time. The decrease of enzyme activity in the infarcted tissue made it much easier to clearly observe ecto-Ca(2+)-ATPase-positive microglia. The enzyme activity of microglia in the ischemic area began to decrease 2 or 4h after embolization and remarkably decreased, except in the perinuclear cytoplasm, apical parts of the processes, and several parts along the processes, 8h after ischemia. By 12h after onset of embolization, the enzyme activity of microglia and infarcted tissue had almost completely disappeared. Ecto-Ca(2+)-ATPase of microglia is likely to play an important role in the metabolism of extracellular nucleotides in the ischemic area immediately after the onset of embolization by means of ecto-enzymes. Thus, the findings of the present study suggest that microglia might serve to protect the infarcted tissue in the ischemic brain.     

Structural equation modeling of the relationship of bone mineral density and its risk factors in Japanese women

Several factors have been reported as risk factors for the development of osteoporosis. In this study, we aimed to examine the relationship among lifestyle factors, biologic factors, and bone mineral density (BMD) using structural equation modeling (SEM). The subjects in the present study consisted of 866 postmenopausal Japanese women aged between 40 and 80 years old. In the analysis by the SEM, we employed a multiple basic model. As the structural variables, lifestyle factors and biologic factors were selected. The goodness of fit index (GFI) of the final model was 0.991 and the Akaike’s information criteria (AIC) showed the lowest value in the peripheral models. The degree of association between biologic factors and BMD was −0.576 (direct association), 0.012 (indirect association), and −0.564 (total association). With regard to the correlation between lifestyle factors and BMD, the degrees of association were 0.085, −0.084, and 0.001, respectively. This study defined a pilot model for factors influencing BMD. Although is remains necessary to conduct further analyses with more valid measurements and constructs, this model indicated that the correlation between BMD and lifestyle factors was lower than that between BMD and biologic factors.     

Intrinsic factors involved in the depression of neuronal activity induced by temperature increase in rat hippocampal neurons

The intrinsic factors involved in the temperature-dependent impairment of neuronal activity in hippocampal CA2-CA1 regions were investigated using optical recording techniques. At 32 degrees C, stimulation of the Schaffer collaterals in the hippocampal CA2 region evoked depolarizing optical responses that spread toward the CA1 region. The optical response was characterized by fast and slow components that were mainly related to the presynaptic action potentials and excitatory postsynaptic response, respectively. The increase of the temperature to 38 degrees C was associated with a reversible depression of the neuronal activity in the hippocampal brain preparations. The depression of neuronal activity was irreversible when the temperature was increased to 40 degrees C. In the presence of 22 mM glucose, the depression of the neuronal activity at 38 degrees C was significantly attenuated. Pyruvate (22 mM), but not lactate (22 mM), also improved the depression of neuronal activity induced by the temperature increase. Adenosine (200 microM) strongly depressed the excitatory postsynaptic response, but not presynaptic action potentials. 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (10 microM), an adenosine A1 receptor blocker, attenuated the adenosine-induced depression of the excitatory postsynaptic response. 8-CPT (10 microM) prevented the impairment of the excitatory postsynaptic response induced by the increase of the temperature to 38 degrees C. In contrast, the depression of presynaptic action potential at 38 degrees C was not prevented by 8-CPT (10 microM). N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and methylcobalamin (10 microM), a vitamin B12 analogue, attenuated the inhibition of pre- and postsynaptic activities induced by the increase of the temperature to 38 degrees C. Glibenclamide, a KATP channel blocker, did not protect neuronal activity from the effects of the increase of the temperature. These results suggest that the heat-induced depression of neuronal activity is mediated by multiple factors, such as impairment of energy metabolism and increase in extracellular adenosine and nitric oxide (NO) levels in hippocampal neurons.     

Protective effect of SM-20550, a selective Na+ - H+ exchange inhibitor, on ischemia-reperfusion-injured hearts

The protective effects of Na+ - H+ exchange inhibitors SM-20550 (SM) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) against ischemia-reperfusion injury were investigated in guinea pig Langendorff hearts. The changes in intracellular pH (pHi), high-energy phosphates, and biologic intracellular active ions ([Na+]i and [Ca2+]i) were regarded using the 31P-NMR and specific fluorescent signals from the heart tissues together with simultaneous recordings of the left ventricular developed pressure (LVDP). The recovery rate of LVDP from ischemia (40 min) by reperfusion was 36.8% in the control experiments, whereas in the presence of SM 10(-7) M, a gradual increase to 75.9% (55.5% with 10(-8) M), in contrast to EIPA (10(-7) M), 47.5% was observed. SM 10(-7) M restored the ATP level by 70% in 40-min reperfusion, which was already higher than the control in the latter half (20-40 min) of the ischemic period. The recovery rate of phosphocreatine by pretreatment of the heart with SM 10(-7) M was 75% in 40 min reperfusion. The pHi estimated from Pi/phosphocreatine chemical shift became highly acidic in ischemic heart so that SM 10(-7) M caused slight but significant pHi reduction from control pHi of 5.89 to 5.75. The level returned to pHi at around 7.38 during 30-40 min reperfusion, and the recovery was significantly greater than the control pHi of 7.24. The fura-2 Ca2+ or SBFI-Na+ signals during Langendorff ischemia heart increased, and rapidly returned to the control level after the reperfusion. SM suppressed the [Na+]i or [Ca2+]i elevation induced in the late stage during ischemia, resulting in LVDP restoration after reperfusion; Diastolic Ca2+ in the end period of ischemia, SM 10(-7) M 194% versus drug-free 220.7%. Na+: SM 10(-7) M 121.6% versus drug-free 128.0%. The present results suggest that the selective Na+ - H+ exchange inhibitor SM is promising as a potent and specific protective agent against ischemia-reperfusion injuries with Ca2+ overload induced via Na+ - H+, Na+ - Ca2+ exchange.     

Retinoid Receptors in Human Breast Carcinoma: Possible Modulators of in Situ Estrogen Metabolism

Retinoid receptors (retinoic acid (RARs) and retinoid X (RXRs) receptors) were immunolocalized in 32 human invasive ductal breast carcinomas. These findings were correlated with clinicopathological parameters to study their biological significance in breast carcinoma. Retinoid receptor immunoreactivity, except for RXR, was detected in the nuclei of carcinoma cells. Percentage of positive cases were RAR 81%, RAR; 6%, RAR; 28%, RXR; 81%, and RXR; 59%. A significant correlation was detected between RAR labeling index (LI), and RXR LI (r=0.667, p<0.001). Results from immunoblotting performed in three cases were consistent with those of immunohistochemistry. There was a significant correlation between RAR LI and 17-hydroxysteroid dehydrogenase (17-HSD) type 1 immunoreactivity (p<0.05). A significant correlation was also detected between RAR (r=0.413, p=0.019) or RXR (r=0.429, p=0.014) LI, and estrogen receptor (ER) LI. In T-47D breast cancer cells, which express RAR, RXR and ER, 17-HSD reductive activity increased 1.76-fold (p<0.001), five days following treatment with 10nM retinoic acid. These data suggest that retinoid receptors modulate various effects of retinoids, including estrogen metabolism in human breast carcinomas.     

Elastic properties of muscle-tendon complex in long-distance runners

The purpose of this study was to investigate the elastic properties of muscle-tendon complex (MTC) in knee extensor muscles and the capacity for elastic energy utilization in long-distance runners (LDR) by comparing with data obtained from untrained individuals (CON). The elongation (L) of the tendon and aponeurosis of vastus lateralis muscle during isometric knee extension was determined by real-time brightness mode ultrasonography, while the subjects developed a gradually increasing torque from 0 (relaxed) to maximal effort (MVC) within 7 s. In addition, performances in two kinds of maximal vertical jumps, i.e. squatting (SJ) and counter-movement jumps (CMJ), were measured. The relationship between L muscle and force (F ) was curvilinear and consisted of an initial region (toe region), characterized by a large increase in L with increasing F, immediately followed by a linear region. The slope of the regression equation for the L-F relationship in the range 50%–100% of MVC was defined as an index of MTC compliance, where the rate of the changes in L to that in muscle F at every 10% of MVC became almost constant. The maximal L (L _max) and MTC compliance were significantly lower in LDR than in CON: 29.9 (SD 3.9) mm in LDR compared to 33.3 (SD 5.5) mm in CON for L _max and 1.55 (SD 0.25) × 10⁻² mm · N⁻¹ in LDR compared to 1.88 (SD 0.82) × 10⁻² mm · N⁻¹ in CON for MTC compliance. Also, LDR showed significantly less elastic energy absorption (E _e) than CON, defined as the area below the L-F relationship curve from 0 to 100% of MVC. Not only jump heights but also the differences between the heights in SJ and CMJ, expressed as the percentage of the height in SJ, were significantly lower in LDR than in CON. The augmentation with counter-movement was significantly correlated to either MTC compliance (r = 0.554, P < 0.05) or E _e (r = 0.563, P < 0.05). Thus, the present results would indicate that MTC of vastus lateralis muscle is less compliant and its potential for energy storage during MTS lengthening is lower in LDR than untrained individuals. These elastic profiles of vastus lateralis muscle in LDR may be associated with their lower performances during CMJ. Accepted: 3 September 1999     

Uterine rupture during pregnancy soon after a laparoscopic adenomyomectomy

Although laparoscopic adenomyomectomy may be a possible risk factor for uterine rupture in subsequent pregnancy, few reports have described it. A 35-year-old woman became pregnant 1 month after laparoscopic adenomyomectomy. At the 28th week, uterine contraction occurred, leading to intravenous ritodrine infusion. Severe abdominal pain and a non-reassuring fetal heart rate occurred abruptly and an emergency cesarean section was carried out. The uterus ruptured at the site of previous surgery of the uterine body, which was reconstructed. The mother and the infant did well postoperatively. We report the second case of uterine rupture during pregnancy subsequent to laparoscopic adenomyomectomy. A history of adenomyomectomy and a short interval to subsequent pregnancy may be risk factors for uterine rupture. (Reprod Med Biol 2007; 6 : 175–177)