Migration ecology of juvenile temperate seabass Lateolabrax japonicus: a carbon stable-isotope approach.

The migration pattern of juvenile temperate seabass Lateolabrax japonicus in the stratified estuary of the Yura River was examined using carbon stable-isotope ratios (δ(13)C). δ(13)C values of mysids, which are the most important prey items for this species, were consistently enriched in the lower estuary and surf zone (LES), while depleted in the freshwater zone (FW). δ(13)C values of juveniles in LES were enriched, while those in FW were depleted, consistent with the δ(13)C difference in prey items. The results of δ(13)C showed that many juveniles migrated upstream from April to June and most of them stayed in FW until at least July. Juveniles that stayed in FW and LES for a relatively longer period (> c. 20 days) showed higher condition factors than those that stayed in FW for a short period (several days). This indicates that residence in FW enabled juveniles to achieve as good a body condition as residence in LES.

Exploring rare cellular activity in more than one million cells by a transscale scope.

In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.

ACO1, a gene for aminocyclopropane-1-carboxylate oxidase: effects on internode elongation at the heading stage in rice.

Although reports on a gene for 1-amino-cyclopropane-1-carboxylate (ACC) oxidase (ACO1) in rice (Oryza sativa L.) suggest that high levels of its transcript are associated with internode elongation of deep-water rice during submergence, the role of ACO1 in rice development is largely unknown. The tissue-specificity of ACO1 expression indicated that its transcript significantly accumulated in lower parts of elongating internodes at the heading stage. Histochemical analysis and in situ hybridization showed that the ACO1 expression was localized in the basal parts of leaf sheaths immediately above nodes or the lower parts of elongating internodes. To further examine the role of ACO1, ACO1-deficient (aco1) and overexpressing (ACO1-OX) mutants were characterized. The total length of the elongated internodes of aco1 mutants was slightly shorter than that of wild-type plants and that of ACO1-OX mutants was longer. Interestingly, expression of the ACC synthase gene ACS1 and ethylene signalling gene OsEIN2 was up-regulated in the aco1 mutants. This study suggests that the ACO1 has a little effect on internode elongation at the heading stage, and that up-regulation of the ACS1 and OsEIN2 expression may attenuate inhibition of internode elongation.

Atypical, bidirectional regulation of cadmium-induced apoptosis via distinct signaling of unfolded protein response.

Cadmium is a widely distributed nephrotoxic metal that causes renal tubular injury. In this report, we investigated involvement of endoplasmic reticulum (ER) stress and individual unfolded protein responses in cadmium-initiated apoptosis of tubular epithelial cells. Cadmium chloride (CdCl(2)) induced expression of endogenous ER stress markers, GRP78, GRP94 and CHOP in vitro and in vivo, and subsequently caused cytological changes typical of apoptosis. Attenuation of ER stress by transfection with ER chaperone GRP78 or ORP150 suppressed CdCl(2)-triggered apoptosis. In response to CdCl(2), phosphorylation of RNA-dependent protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2alpha (eIF2alpha) was observed. Enhanced phosphorylation of eIF2alpha attenuated, whereas inhibition of eIF2alpha exacerbated CdCl(2)-induced apoptosis. Activating transcription factor 6 (ATF6) was also activated by CdCl(2) and blockade of this process suppressed induction of CHOP and thereby improved cell survival. CdCl(2) also triggered activation of the inositol-requiring ER-to-nucleus signal kinase 1 (IRE1)-X-box-binding protein 1 (XBP1) pathway and inhibition of XBP1 attenuated apoptosis independent of GRP78 and CHOP. c-Jun N-terminal kinase (JNK), another molecule downstream of IRE1, was also phosphorylated by CdCl(2) and its inhibition attenuated apoptosis. These results evidenced bidirectional regulation of apoptosis in cadmium-exposed cells. The ATF6 and IRE1 pathways cooperatively caused apoptosis via induction of CHOP, activation of XBP1 and phosphorylation of JNK, and the PERK-eIF2alpha pathway counteracted the proapoptotic processes.

Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse.

JMJD2B is a histone demethylase enzyme that regulates gene expression through demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be responsible for neurodevelopmental disorders, the function of JMJD2B in the central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B has a critical role in the development of the CNS. We observed JMJD2B expression, which was especially strong in the hippocampus, throughout the CNS from embryonic periods through adulthood. We generated neuron-specific JMJD2B-deficient mice using the cre-loxP system. We found an increase in total spine number, but a decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient mice exhibited hyperactive behavior, sustained hyperactivity in a novel environment, deficits in working memory and spontaneous epileptic-like seizures. Together these observations indicate that JMJD2B mutant mice display symptoms reminiscent of neurodevelopmental disorders. Our findings provide evidence for the involvement of histone demethylation in the formation of functional neural networks during development.

Hepatic portal venous gas associated with nonocclusive mesenteric ischemia in a hemodialysis patient.

Hepatic portal venous gas (HPVG) has been rarely described in chronic hemodialysis patients. We report a case of HPVG in a 59-year-old female patient with hemodialysis-dependent chronic renal failure due to diabetes who presented with acute onset of abdominal pain. Abdominal CT demonstrated the presence of gas in the portal veins. However, on laparotomy, no evidence of bowel necrosis or perforation could be found. HPVG seemed to be caused by nonocclusive mesenteric ischemia (NOMI), an increasingly recognized complication in hemodialysis patients. The patient responded favorably to intravenous hyperalimentation and antibiotics.

Exendin-4, glucagon-like peptide-1 receptor agonist, enhances isoflurane-induced preconditioning against myocardial infarction via caveolin-3 expression.

OBJECTIVE: To investigate the cardioprotective effects of isoflurane and exendin-4 against myocardial ischemia/reperfusion injury and the signaling pathways through which these effects are mediated. MATERIALS AND METHODS: For infarct size measurements, anesthetized mice were subjected to 30 min of coronary artery occlusion followed by 2 h of reperfusion. Wild-type or caveolin-3 knockout mice received isoflurane, exendin-4, or isoflurane with exendin-4 before ischemia index determination. Caveolin-3 expression in the heart was measured by immunoblotting. RESULTS: Myocardial infarct size was smaller in the isoflurane- [1.0 minimum alveolar concentration (MAC)] or exendin-4- (30 ng/kg i.v.) treated groups than the controls. Infarct size was not affected by isoflurane at 0.5 MAC or 3 ng/kg i.v. exendin-4, but the combination of these treatments reduced infarct size. Pharmacological preconditioning (isoflurane at 1.0 MAC, 30 ng/kg i.v. exendin-4, or isoflurane at 0.5 MAC with 3 ng/kg i.v. exendin-4) increased caveolin-3 protein expression in the heart after infarct induction. The cardioprotective effects of isoflurane, exendin-4, and isoflurane with exendin-4 were abolished in caveolin-3 knockout mice. CONCLUSIONS: The combination of isoflurane and exendin-4 reduced infarct size, but it was not more effective than either agent alone, and the cardioprotective effects of these agents are mediated by caveolin-3 expression.

Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder that is characterized by attention difficulties, impulsivity, and hyperactivity. A non-stimulant drug, atomoxetine (ATX), which is a selective noradrenaline reuptake inhibitor, is widely used for ADHD because it exhibits fewer adverse effects compared to conventional psychostimulants. However, little is known about the therapeutic mechanisms of ATX. ATX treatment significantly alleviated hyperactivity of pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice with C57BL/6J and 129S6/SvEvTac hybrid background. ATX also improved impaired novel object recognition memory and prepulse inhibition in PACAP(-/-) mice with CD1 background. The ATX-induced increases in extracellular noradrenaline and dopamine levels were significantly higher in the prefrontal cortex of PACAP(-/-) mice compared to wild-type mice with C57BL/6J and 129S6/SvEvTac hybrid background. These results suggest that ATX treatment-induced increases in central monoamine metabolism may be involved in the rescue of ADHD-related abnormalities in PACAP(-/-) mice. Our current study suggests that PACAP(-/-) mice are an ideal rodent model with predictive validity for the study of ADHD etiology and drug development. Additionally, the potential effects of differences in genetic background of PACAP(-/-) mice on behaviors are discussed.

Comparison of effectiveness of an 8-mm versus a 4-mm tip electrode catheter for radiofrequency ablation of typical atrial flutter.

An 8-mm catheter does not appear superior to 4-mm tip electrode for atrial flutter ablation. The potential advantage of allowing higher energy delivery on a larger surface is compensated by the lack of consistent contact with the endocardial surface.

Exercise-induced coronary spasm: comparison of treadmill and bicycle exercise in patients with vasospastic angina.

BACKGROUND: We investigated whether exercise-induced coronary spasms are influenced by the different exercise modes. METHODS: We compared ischaemic ECG responses in 67 patients with vasospastic angina who underwent both treadmill and bicycle ergometer exercise and also coronary angiography. RESULTS: ECG ST-segment elevation was provoked more frequently during treadmill exercise than it was during bicycle exercise (19 versus 9%, P < 0.05). Of 45 patients without significant coronary stenosis (coronary artery luminal diameter narrowing < 75%), 19 patients manifested ST-segment depression during treadmill exercise, whereas only seven patients did during bicycle exercise (42 versus 16%, P < 0.01). All patients with ST-segment elevation or depression during bicycle ergometer exercise also had ST-segment changes during treadmill exercise. Although higher systemic blood pressure levels and lower heart rates were found during bicycle exercise compared with during treadmill exercise the pressure-rate products at peak exercise did not differ between the two exercise tests. CONCLUSIONS: It seems that treadmill and bicycle exercise are different stressors in patients with vasospastic angina, and that coronary spasms are provoked more frequently during treadmill exercise than they are during bicycle exercise. The cause of this difference is not known, but it may be related in part to the difference in systemic haemodynamic or neurohumoral response.

Novel method for the preparation of controlled-release theophylline granules coated with a polyelectrolyte complex of sodium polyphosphate-chitosan.

A novel method for the preparation of theophylline granules coated with a polyelectrolyte complex of sodium tripolyphosphate and chitosan was developed. The theophylline granules containing sodium tripolyphosphate were stirred in an HCl solution of chitosan. During the mixing, the dissolved sodium tripolyphosphate in the granule moved to the surface and reacted with the chitosan, resulting in the formation of the polyelectrolyte complex film. The factors affecting the drug content, the particle size, and the coating-film thickness of the resultant coated granules were determined. The theophylline content in the coated granule decreased with increasing content ratio of sodium tripolyphosphate to theophylline in the original granule and with increasing chitosan concentration in the coating solution. The coated granule size increased with increasing chitosan concentration in the coating solution and with decreasing agitation speed. The coating-film thickness increased with an increase in the chitosan concentration, the pH of the coating solution, and the sodium tripolyphosphate to theophylline content ratio in the original granule. The drug-release pattern of the coated granules followed zero-order kinetics and the release rates were significantly reduced compared with that of the original granule.

Liquid-liquid extraction separation and sequential determination of plutonium and americium in environmental samples by alpha-spectrometry.

A procedure is described by which plutonium and americium can be determined in environmental samples. The sample is leached with nitric acid and hydrogen peroxide, and the two elements are co-precipitated with ferric hydroxide and calcium oxalate. The calcium oxalate is incinerated at 450 degrees and the ash is dissolved in nitric acid. Plutonium is extracted with tri-n-octylamine solution in xylene from 4M nitric acid and stripped with ammonium iodide/hydrochloric acid. Americium is extracted with thenoyltrifluoroacetone solution in xylene at pH 4 together with rare-earth elements and stripped with 1M nitric acid. Americium and the rare-earth elements thus separated are sorbed on Dowex 1 x 4 resin from 1M nitric acid in 93% methanol, the rare-earth elements are eluted with 0.1M hydrochloric acid/0.5M ammonium thiocyanate/80% methanol and the americium is finally eluted with 1.5M hydrochloric acid in 86% methanol. Plutonium and americium in each fraction are electro-deposited and determined by alpha-spectrometry. Overall average recoveries are 81% for plutonium and 59% for americium.

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -2. Subacute toxicity in rats by subcutaneous administration (author's transl)].

Subacute toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a new synthetic corticosteroid, was studied in rats, using betamethasone 17-valerate (BV) and hydrocortisone 17-butyrate (HB) as the reference drugs. HBP was subcutaneously injected to rats at the daily doses of 0.08, 0.4, 2.0, 10 and 50 mg/kg for 30 days. BV and HB were also administered at the daily doses of 0.08, 0.4 and 2.0 mg/kg. The recovery test was performed for 4 weeks after administration of HBP, BV and HB. The suppression of body weight gain by HBP was observed at the doses more than 0.08 mg/kg in male and more than 2.0 mg/kg in female rats. In addition, at the doses more than 0.4 mg/kg of HBP induced the dose-dependent symptoms such as decrease in the number of circulating white blood cells, lymphocyte counts and S-ALP level, increase in total cholesterol, GOT and GPT level of serum, and regressive changes in adrenals, lymphatic and hematopoietic tissues. There were fatal cases in rats given 50 mg/kg of HBP. These changes are considered to be common phenomena to other corticosteroids, and less toxic in female than male rats. Changes of symptoms caused by the administration of HBP 2.0 mg/kg were almost recovered after withdrawal. The toxicities of three corticosteroids were in the order of BV greater than HB greater than or equal to HBP in strength. As the result, maximum non-toxic dose of HBP was estimated to be 0.08 mg/kg in female and lower than that in male rats.

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -4. Chronic toxicity in rats by subcutaneous administration (author's transl)].

Chronic toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a new synthetic corticosteroid, was studied in rats. HBP was subcutaneously injected to rats as the daily doses of 0.001, 0.01, 0.01, 1.0 and 3.0 mg/kg for 6 months, and the following recovery test was carried out for 4 weeks. Hydrocortisone 17-butyrate (HB) and betamethasone 17-valerate (BV) were used as the reference drugs at the doses of 0.1, 1.0 and 3.0 mg/kg. The suppression of body weight gain by the administration of HBP was observed at the doses more than 1.0 mg/kg in male and more than 0.1 mg/kg in female, and the dead animals were sent at the highest dose of HB and BV. Mainly at the doses more than 0.1 mg/kg HBP induced the dose-dependent symptoms such as decrease in the number of white blood cells and total protein level in serum, and increase in total cholesterol, GOT and GPT level in serum, and atrophic changes of adrenals, lymphatic tissues, skin and subsexual organs. No usual abnormality was recognized at the doses less than 0.01 mg/kg of HBP. These symptoms were more toxic in male, and the strength of toxicity was in the order of BV greater than HB greater than HBP. Many of these findings have known as common effects of corticosteroids. The changes observed in this study were almost recovered after withdrawal of HBP at the doses less than 0.1 mg/kg. As the result, it was suggested that the maximum non-toxic dose of HBP was 0.001 mg/kg.

[Implementation and evaluation of public relations activity in a community health program].

OBJECTIVE: This study evaluated public relations activity in a community health program in order to develop effective strategies to attract the public attention for the program. METHODS: An intervention study was conducted on public relations for "Nutrition Seminar for Citizens," sponsored by the Health Department of Machida City, Tokyo, in October, 1999. One ward in the city was selected as an intervention area, and another ward which had similar demographic and geographic characteristics was chosen as a control area. Two target populations were defined; one was women in their 20s to 60s (#1) and the other was those who had previously never utilized community health programs sponsored by the city (#2). Handbills were used as the medium for public relations for the seminar. These announced the time, place and content of the nutrition seminar and were designed by authors with special attention to catchphrases, colors and fonts. Handbills were distributed in the intervention area through elementary schools, local voluntary organizations and local health volunteers. In addition, the authors directly handed them out to people in front of two supermarkets in the town. The sources of seminar information were requested from the participants of the Nutrition Seminar with a self-administered questionnaire. RESULTS: 1. The percentage of participants who received the seminar information from handbills was higher than that of those who used monthly newsletters from the city as a source of information. 2. The percentage of participants from the intervention area was higher than that from the control area. 3. Regarding target populations #1 and #2, there were no differences in participation rates between the intervention and control area. 4. Among the four distribution routes, the local voluntary organization route was the most effective for attracting participants. CONCLUSIONS: The results show that handbills can be an effective medium for pubic relations to increase the number of participants in community health programs. Also, local voluntary organizations can play a crucial role in information transfer in the community because of their high credibility. On the other hand, we could not reach specified target populations with the medium. Further surveys are needed to establish optimal media and routes to reach appropriate target populations in health programs.

[MR diffusion-weighted imaging of cerebral infarction].

MR diffusion-weighted imaging was performed to investigate changes in water diffusion in patients with cerebral infarction, and diffusion-weighted images (DWI) were compared with T2-weighted images (T2WI). Acute and subacute infarcts were seen as areas of high intensity on DWI and showed lower apparent diffusion coefficients (ADCs), while chronic infarcts showed a relative increase in ADCs. The relative ADC increased progressively over time, becoming renormalized at 3 to 4 weeks, and was elevated in the chronic state. On DWI, infarcts as small as 5 to 6 mm in diameter and lesions adjacent to the ventricular or subarachnoid space could be readily identified. DWI was useful for distinguishing acute lesions from chronic lesions in patients with multiple cerebral infarction, and provided valuable pathophysiologic information on the course of ischemic stroke evolution.

[A case of metastatic liposarcoma originating in the retroperitoneum successfully treated with combination chemotherapy].

We reported a 36-year-old woman with metastatic liposarcoma originating in the retroperitoneum, which responded well to adjuvant chemotherapy. The primary tumor was removed by surgery. Two months later, the patient developed metastasis to the brain, and to the lung four months later. Metastatic liposarcomas to the brain generally are extremely rare. The patient was treated with combination chemotherapy using cyclophosphamide, vincristine, adriamycin, and dacarbazine (CYVADIC). After she was examined, the former two drugs were alternated with vindesine and ifosfamide, and another regimen with cisplatin and etoposide was given after a three-week interval. As a result, both of the metastases totally disappeared. No recurrent lesion has been noted for two years. Although the role of chemotherapy for liposarcoma has not been well defined and little data support its use in an adjuvant setting, this combination chemotherapy seemed to be effective for advanced liposarcoma.

[A case of congenital long QT syndrome associated with T wave alternans].

A case was presented in which a rare T wave alternans occurred in association with congenital long QT syndrome. A 71-year-old woman, who had experienced several syncopal attacks per year for the previous forty years, was admitted for further evaluation of the syncope. She had a family history of sudden death (sister) and QT prolongation (son). Electrocardiogram showed a corrected QT interval of 0.68 seconds. Treadmill exercise-tolerance test revealed both T wave alternans immediately after exercise and torsades de pointes 150 seconds after exercise. The syncope was induced by the mental excitation. A prolonged corrected QT interval reduced from 0.70 seconds to 0.58 seconds by the correction of her serum potassium and magnesium. The effect of propranolol, verapamil, phenytoin or mexiletine on T wave alternans and ventricular arrhythmia was evaluated by the treadmill exercise-tolerance test. The treatment with propranolol was most effective.

[Acute and chronic effects of a new oral inotropic agent, ibopamine hydrochloride, on hemodynamic and metabolic responses to ergometer exercise in patients with severe congestive heart failure].

The hemodynamic and metabolic effects of ibopamine, an orally active 3,4-diisobutylic ester of N-methyl-dopamine, at rest and during exercise, were evaluated in 8 patients with severe congestive heart failure, initially at 2 hrs after oral 100 mg and after 4 weeks of maintenance therapy (100 mg, 3 times a day). At rest, a single dose of ibopamine increased CI, SVI and SWI, and reduced PCWP, PAm, RA and PVR. These beneficial hemodynamic effects were maintained during supine bicycle exercise: CI and SVI increased markedly (p less than 0.05) and PCWP, PAm, RA and SVR increased at a lower extent (p less than 0.05) after ibopamine than on control conditions. After chronic therapy with the drug, LVDd and CTR decreased (p less than 0.05) and exercise tolerance time increased (p less than 0.01). HR, BPm, double product, norepinephrine, epinephrine, renin activity, aldosterone and lactate/pyruvate did not change significantly after administration of ibopamine. Clinical responses after 4 weeks of maintenance therapy were good in 4 cases and fair in 1 case. No adverse effects were observed. Therefore, ibopamine seems to have not only a positive inotropic action, but also a potent vasodilating action, leading to both afterload and preload reduction and so to be useful for the treatment of severe congestive heart failure at rest and during exercise after acute and chronic therapy with the drug.