Effects of age at estrogen replacement therapy initiation on trabecular bone score in Japanese adults with Turner syndrome.

The effects of the age at estrogen replacement therapy (ERT) initiation on bone quality in Turner syndrome were evaluated using trabecular bone score. Early puberty ERT positively correlated with increase in bone quality. Early initiation of ERT is necessary for the acquisition of bone quality as well as bone density. INTRODUCTION: Studies have reported associations between bone mineral density and estrogen replacement therapy (ERT) in Turner syndrome (TS) patients; however, few studies exist on the effect on bone quality. The aim of this study was to evaluate the effects of the age at ERT initiation on bone quality of Japanese TS patients, cross-sectionally and longitudinally. METHODS: Cross-sectionally, 95 TS patients were divided into three groups based on their age at initiation of ERT: A (12-14 years, 11 patients), B (15-17 years, 47 patients), and C (over 18 years, 37 patients). To assess bone quality, trabecular bone score (TBS) was used. The effects of age at initiation and duration of ERT on TBS were examined using multiple regression analysis. In the longitudinal study, 48 patients who underwent dual-energy X-ray absorptiometry multiple times were divided into three groups: D (12-14 years, 8 patients), E (15-17 years, 18 patients), and F (over 18 years, 22 patients). Each group was analyzed for the rate of change in TBS per year. RESULTS: Cross-sectionally, the TBS showed significant differences among the three groups (TBS A, 1.302; B, 1.299; C, 1.245) (p = 0.013); group C was significantly lower than B (p = 0.014); bone quality was degraded. Multiple regression analysis revealed that age at ERT initiation significantly affected the increase in TBS (p = 0.002). Longitudinally, the rate of change of TBS was not significantly different in the three groups (p = 0.73). CONCLUSION: Early initiation of ERT may have positive effects on bone quality in TS. Large prospective studies will be needed.

Dopamine D(2)-like receptors selectively block N-type Ca(2+) channels to reduce GABA release onto rat striatal cholinergic interneurones.

1. The modulatory roles of dopamine (DA) in inhibitory transmission onto striatal large cholinergic interneurones were investigated in rat brain slices using patch-clamp recording. 2. Pharmacologically isolated GABA(A) receptor-mediated IPSCs were recorded by focal stimulation within the striatum. Bath application of DA reversibly suppressed the amplitude of evoked IPSCs in a concentration-dependent manner (IC(50), 10.0 microM). 3. A D(2)-like receptor agonist, quinpirole (3-30 microM), also suppressed the IPSCs, whereas a D(1)-like receptor agonist, SKF 81297, did not affect IPSCs. Sulpiride, a D(2)-like receptor antagonist, blocked the DA-induced suppression of IPSCs (apparent dissociation constant (K(B)), 0.36 microM), while a D(1)-like receptor antagonist, SCH 23390 (10 microM), had no effect. 4. DA (30 microM) reduced the frequency of spontaneous miniature IPSCs (mIPSCs) without changing their amplitude distribution, suggesting that GABA release was inhibited, whereas the sensitivity of postsynaptic GABA(A) receptors was not affected. The effect of DA on the frequency of mIPSCs was diminished when extracellular Ca(2+) was replaced by Mg(2+) (5 mM), indicating that DA affected the Ca(2+) entry into the presynaptic terminal. 5. An N-type Ca(2+) channel selective blocker, omega-conotoxin GVIA (omega-CgTX, 3 microM), suppressed IPSCs by 65.4 %, whereas a P/Q-type Ca(2+) channel selective blocker, omega-agatoxin IVA (omega-Aga-IVA, 200 nM), suppressed IPSCs by 78.4 %. Simultaneous application of both blockers suppressed IPSCs by 95.9 %. Assuming a 3rd power relationship between Ca(2+) concentration and transmitter release, the contribution of N-, P/Q- and other types of Ca(2+) channels to presynaptic Ca(2+) entry is estimated to be, respectively, 29.8, 40.0 and 34.5 % at this synapse. After the application of omega-CgTX, DA (30 microM) no longer affected IPSCs. In contrast, omega-Aga-IVA did not alter the level of suppression by DA, suggesting that the action of DA was selective for N-type Ca(2+) channels. 6. A G protein alkylating agent, N-ethylmaleimide (NEM), significantly reduced the DA-induced suppression of IPSCs. 7. These results suggest that presynaptic D(2)-like receptors are present on the terminals of GABAergic afferents to striatal cholinergic interneurones, and down-regulate GABA release by selectively blocking N-type Ca(2+) channels through NEM-sensitive G proteins.

Presynaptic dopamine D2-like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones.

1. The effects of dopamine (DA) on non-NMDA glutamatergic transmission onto dopaminergic neurones in the ventral tegmental area (VTA) were examined in rat midbrain slices using the whole-cell patch-clamp technique. EPSCs in dopaminergic neurones evoked by focal stimulation within the VTA were reversibly blocked by 5 microM CNQX in the presence of bicuculline (20 microM), strychnine (0.5 microM) and D-amino-5-phosphonopentanoic acid (D-AP5, 25 microM). 2. Bath application of DA reduced the amplitude of EPSCs up to 65.1 +/- 9. 52% in a concentration-dependent manner between 0.3-1000 microM (IC50, 16.0 microM) without affecting the holding current at -60 mV measured using a Cs+-filled electrode. 3. The effect of DA on evoked EPSCs was mimicked by the D2-like receptor agonist quinpirole but not by the D1-like receptor agonist SKF 81297, and was antagonized by the D2-like receptor antagonist sulpiride (KB, 0.96 microM), but not by the D1-like receptor antagonist SCH 23390 (KB, 228.6 microM). 4. Dopamine (30 microM) reduced the mean frequency of spontaneous miniature EPSCs (mEPSCs) without affecting their mean amplitude, and the DA-induced effect on the mEPSCs was dependent on the external Ca2+ concentration. 5. These results suggest that afferent glutamatergic fibres which terminate on VTA dopaminergic neurones possess presynaptic D2-like receptors, activation of which inhibits glutamate release by reducing Ca2+ influx.

Gene structure and quinol oxidase activity of a cytochrome bd-type oxidase from Bacillus stearothermophilus.

Gram-positive thermophilic Bacillus species contain cytochrome caa3-type cytochrome c oxidase as their main terminal oxidase in the respiratory chain. We previously identified and purified an alternative oxidase, cytochrome bd-type quinol oxidase, from a mutant of Bacillus stearothermophilus defective in the caa3-type oxidase activity (J. Sakamoto et al., FEMS Microbiol. Lett. 143 (1996) 151-158). Compared with proteobacterial counterparts, B. stearothermophilus cytochrome bd showed lower molecular weights of the two subunits, shorter wavelength of alpha-band absorption maximum due to heme D, and lower quinol oxidase activity. Preincubation with menaquinone-2 enhanced the enzyme activity up to 40 times, suggesting that, besides the catalytic site, there is another quinone-binding site which largely affects the enzyme activity. In order to clarify the molecular basis of the differences of cytochromes bd between B. stearothermophilus and proteobacteria, the genes encoding for the B. stearothermophilus bd was cloned based on its partial peptide sequences. The gene for subunit I (cbdA) encodes 448 amino acid residues with a molecular weight of 50195 Da, which is 14 and 17% shorter than those of Escherichia coli and Azotobacter vinelandii, respectively, and CbdA lacks the C-terminal half of the long hydrophilic loop between the putative transmembrane segments V and VI (Q loop), which has been suggested to include the substrate quinone-binding site for the E. coli enzyme. The gene for subunit II (cbdB) encodes 342 residues with a molecular weight of 38992 Da. Homology search indicated that the B. stearothermophilus cbdAB has the highest sequence similarity to ythAB in B. subtilis genome rather than to cydAB, the first set of cytochrome bd genes identified in the genome. Sequence comparison of cytochromes bd and their homologs from various organisms demonstrates that the proteins can be classified into two subfamilies, a proteobacterial type including E. coli bd and a more widely distributed type including the B. stearothermophilus enzyme, suggesting that the latter type is evolutionarily older.

A novel method of time series analysis, and an application to the study of human sleep electroencephalogram.

A new mathematical method was developed to analyze time series. Applications of this method to the delta component of all-night sleep electroencephalogram (EEG) revealed new variations with double-rapid eye movement (REM)-sleep interval. The proposed method entails repeated application of the least squares spectrum. First, the conventional least squares spectrum calculation is applied to the time series. Using the parameters of the peak components in the obtained spectrum, an intermediate time series is reconstructed. The residual time series is made by subtracting the intermediate time series from the previous time series. Next, the least squares calculation is again applied to the residual time series. These procedures are repeated until the component cannot be detected. We named this new method the Repeated Least Squares Spectrum for the Residual (RLSSR). The remarkably similar time series pattern to the original time series can be reconstructed using the obtained parameters of all components. The EEG was recorded during all-night sleep on five consecutive nights in five healthy adults, by a total of 25 recordings. The variations of the height of successive 1-min delta components in the EEG were analyzed. In addition, two autocorrelograms were made for two time series patterns. These were reconstructed from two specific sets of the components obtained by the proposed analysis method. These autocorrelograms demonstrated a long-span variation with near double-REM-sleep interval in not a few records. Based on these data, it appears that the delta component of sleep EEG does not always demonstrate a simple gradually decreasing trend.

Alpha-delta sleep in a case with non-24 h sleep-wake syndrome: quantitative electroencephalogram analysis of alpha and delta band waves.

Four all-night polysomnograms of a 39-year-old male patient with non-24 h sleep-wake syndrome were recorded. We analysed electroencephalograms (EEG) with the power spectrum method and the wave pattern recognition analysis of Fujimori. The EEG of the rest waking condition showed normal patterns. High-voltage diffuse alpha band waves were observed in sleep stages 2, 3 and 4. The integrated area of the alpha band waves in the analysis epochs showed a strong positive correlation to the delta band components in the power spectrum of the same epoch during sleep (correlation coefficients r = 0.762-0.815). Alpha band waves during sleep were clearly different from the alpha waves in the rest waking condition, with respect to slower peak frequency and the frontal dominant voltage distribution.

[Smoking habits in chronic schizophrenics].

The smoking habits of 48 chronic schizophrenics who were inpatients of private psychiatric were examined. Subjects were divided into three groups; non-smokers, moderate smokers and heavy smokers, and tested by Fagerstrom's Tolerance Questionnaire (FTQ) as a tobacco dependence evaluation, and Bender Gestalt Test (BGT) and Benton Visual Retention Test (BVRT) as a neuropsychological battery. In addition, we used the Scales for the Assessment of Negative Symptoms (SANS) to evaluate the degree of schizophrenic negative symptoms, confirming the correlation between SANS score and the amount of nicotine intake or FTQ item. From the results of FTQ scores and their correlation with SANS scores, the amount of nicotine intake was significantly related to the severity of schizophrenic negative symptoms including affective blunting, poverty of thinking and attention impairment. BGT and BVRT showed disturbances in visual-motor gestalt function, and attention and memory, in chronic schizophrenics who smoked, especially in heavy smokers. These results suggest that smoking behavior in chronic schizophrenics might increase the individual vigilance against negative symptoms, from the perspective of self-medication.

[Amotivational syndrome of chronic organic solvent abusers--neuropsychological study].

It is conceivable that many of chronic organic solvent abusers have shown "Amotivational Syndrome" that is often seen in marijuana abuse. This syndrome revealed various psychiatric symptoms such as diminution of ambition, productivity and motivation. However, the pathogenesis of this syndrome is not elucidated. In present study, we examined 31 patients who showed amotivational syndrome (AS) induced by chronic organic solvents abuse, using neuropsychological battery including Benton Visual Retention Test (BVRT) and Bender Gestalt Test (BGT). In BVRT, there was a differences between AS and controls in the items of number of errors, omission, distortion and misplacement. In BGT, each Figure's score except I and VIII has changed and total score was 43.25 (vs control; 23.05), corresponding to 9-10 year old development in AS. These results suggest that organic solvent-induced AS is closely related with neurological and cognitive impairments in the central nervous system.

[Psychological problem due to long-term organic solvent abuse].

Organic solvent abuse in adolescents has become a serious social problem. One of the reasons for this is the relationship to juvenile delinquency, and another is that it leads to various clinical symptoms including disturbance of consciousness, hallucinations, fantasia and apathy. In this study, using a health questionnaire that is composed of 33 psychiatric and 29 physical items and the Rorschach Test, we investigated these symptoms and the psychodynamics of personality respectively. The principal component analysis obtained for the health questionnaire extracted four factors as follows: 1) feelings of general fatigue and somatic symptoms, 2) feelings of guilt and self blame, 3) low self esteem and withdrawal adaptation, and 4) unreasonable anxiety and sleeping disturbance. The results of Rorschach Test supported the loss of libido, disability of reality testing and ego vulnerability in organic solvent abusers. This research strongly suggests that apathetic or depressive mood in chronic organic solvent abusers relates with loss of drive.

Delta component variations in human sleep electroencephalogram.

All night sleep was recorded polygraphically on 14 healthy adults, once for each person, and EEG was analyzed with bandpass filters. The integrated values during successive 10 second epochs were recorded consecutively at 1 mm intervals, separately for each frequency band. The variations of integrated values for long time span were clearly observed. The findings on 1-2 Hz component are reported exclusively in this report. (1) Four variation patterns were classified on the variations of integrated values of 1-2 Hz band component; long undulation, short undulation, irregular undulation and slight fluctuation. Short undulation was superimposed on long undulation. Long undulation had a gradually increasing slope, a plateau and steeply decreasing slope. Irregular undulation showed generally irregular fluctuations, without any definite variation patterns. During slight fluctuation the variations were small. Long undulation and irregular undulation corresponded to slow-wave sleep and slight fluctuation corresponded to REM sleep. The mean duration of each long undulation and irregular undulation was 31.2 and 11.9 minutes, respectively. In long undulations, 62.8% of the time was occupied by Stage 2 and the lesser ratio by Stages 3 and 4. In irregular undulation 89.1% of the time corresponded to Stage 2. (2) One sleep cycle was composed of the three sleep states which were accompanied with variation patterns, long undulation, irregular undulation and slight fluctuation. The sequence of the appearance of the former two patterns in one sleep cycle was classified into four types. About half of the sleep cycles in all records exhibited Type 1; the pattern started with long undulation, after one or several long undulations followed by irregular undulation and proceeded to slight fluctuation. The average number of long indulation in one sleep cycle was 1.58. (3) On all records, the highest long undulations appeared in the first cycle of all night sleep, in both frontal and central areas. In the occipital area, some of the highest crests appeared in the second cycle. When the highest of long undulations appeared, the height tended to decrease prior to wakening. The crest line of long undulation in frontal and central areas crossed in the latter period of all night sleep, in five controls. The mean voltage of long undulation in frontal, central and occipital areas was 52.4, 42.5 and 23.5 microvolts, respectively. The underlying physiological mechanism of delta waves in human sleep EEG and possible brain structures essential for long undulation and irregular undulation were discussed from both the clinical and experimental aspects.