Three-dimensional SAFT imaging for anisotropic materials using photoacoustic microscopy.

A pulsed laser illuminates a target zone that causes rapid thermoelastic expansion, generating broadband high-frequency ultrasonic wave (photoacoustic wave, PA wave). We developed a PA microscopy (PAM) with a confocal area of laser and ultrasonic wave for applications in nondestructive testing (NDT). The synthetic aperture focusing technique (SAFT) is applied in the PAM for the three-dimensional (3D) imaging of interior flaws. Here, we report proof-of-concept experiments for the NDT of a subsurface flaw in a thin laminar material. Graphical abstract (a) shows a specimen of carbon-fiber-reinforced plastic (CFRP) with an artificial delamination. Here, it should be noted that the group velocity varies directionally due to the strong anisotropy of the CFRP specimen (see Graphical abstract (b)). By considering the group velocity distribution in the SAFT, the shape and location of the subsurface delamination were accurately estimated as shown in Graphical abstract (c). Coating the surface of the CFRP specimen with a light-absorbent material improved the amplitude of the PA wave. This finding showed that the signal-to-noise ratio of the waves scattered from the flaws can be improved.

Why chronically ill children face challenges in regular classrooms: perspectives from nursing teachers in Japan.

BACKGROUND: Chronically ill children are increasingly expected to join their peers in regular classrooms. However, sometimes schools do not provide adequate assistance. This study explores nursing teachers' thoughts and experiences on integrating such students into regular classrooms in Japan. METHODS: We analysed 79 essays written by nursing teachers collectively titled 'The challenges of having chronically ill children in regular classrooms'. We conducted a qualitative study using Kinoshita's Modified Grounded Theory Approach. RESULTS: Nursing teachers identified three main obstacles: insufficient resources to support chronically ill students, parents not playing a supporting role in aiding them at school and a regular classroom not being suitable for them. However, collaborating with the children's medical staff proved successful at integrating them into regular classrooms. CONCLUSIONS: Given these obstacles, it seems very difficult for nursing teachers to lead the way toward establishing cooperative support systems for the children. Instructions from medical staff could empower teachers to set up such systems.

Disclosing haemophilia at school: strategies employed by mothers of children with haemophilia in Japan.

INTRODUCTION: Most children with haemophilia in Japan study in mainstream schools. However, many mothers have difficulty deciding whether to inform teachers of their child's haemophilia because of the accompanying potential discrimination and prejudice, particularly after the press coverage on the HIV scandal in the 1980s. AIMS: We therefore aim to explore and describe disclosure strategies of mothers of children with haemophilia. METHODS: A qualitative study was conducted using the modified grounded theory approach to explore disclosure strategies of mothers of children with haemophilia. Semi-structured interviews were conducted with 19 selected mothers (12 children were HIV positive and 7 were HIV-negative). RESULTS: In the pre-HIV/AIDS crisis period, the kind of strategy employed - full disclosure, conditional full disclosure and partial disclosure - depended on the extent of mothers' fears about mainstream schools refusing admission because of their child's haemophilia. After the HIV/AIDS crisis in the 1980s in Japan, the three categories of strategies employed by mothers of children with haemophilia were limited disclosure, non-disclosure and full disclosure. These depended on mothers' expectations of discrimination towards their child because of the social stigma around haemophilia and being HIV-positive. CONCLUSION: For children with haemophilia to feel safe attending school, public schools must establish care management and anti-discrimination systems for children with chronic diseases, thus assuring parents of their children's welfare at school.

A new aspect of the TrkB signaling pathway in neural plasticity.

In the central nervous system (CNS), the expression of molecules is strictly regulated during development. Control of the spatiotemporal expression of molecules is a mechanism not only to construct the functional neuronal network but also to adjust the network in response to new information from outside of the individual, i.e., through learning and memory. Among the functional molecules in the CNS, one of the best-studied groups is the neurotrophins, which are nerve growth factor (NGF)-related gene family molecules. Neurotrophins include NGF, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4/5 in the mammal. Among neurotrophins and their receptors, BDNF and tropomyosin-related kinases B (TrkB) are enriched in the CNS. In the CNS, the BDNF-TrkB signaling pathway fulfills a wide variety of functions throughout life, such as cell survival, migration, outgrowth of axons and dendrites, synaptogenesis, synaptic transmission, and remodeling of synapses. Although the same ligand and receptor, BDNF and TrkB, act in these various developmental events, we do not yet understand what kind of mechanism provokes the functional multiplicity of the BDNF-TrkB signaling pathway. In this review, we discuss the mechanism that elicits the variety of functions performed by the BDNF-TrkB signaling pathway in the CNS as a tool of pharmacological therapy.

Efficient gene transduction of neurons by lentivirus with enhanced neuron-specific promoters.

In the field of basic and clinical neurosciences, it is important to develop a method for easy delivery and persistent expression of transgene in central neurons. We firstly generated lentiviral vectors with five kinds of neuron-specific promoters, such as synapsin I (SYN), calcium/calmodulin-dependent protein kinase II, tubulin alpha I, neuron-specific enolase and platelet-derived growth factor beta chain promoters and then novel hybrid promoters by fusing cytomegalovirus enhancer (E) to those neuron-specific promoters. Neuron-specific expression of green fluorescent protein (GFP) with those promoters was examined in vivo by injecting the lentiviral vectors into the rat neostriatum, thalamus and neocortex. Among all the promoters, SYN promoter displayed the highest specificity for neuronal expression in all the regions examined (more than 96%). Although GFP production by the hybrid promoters was about 2-4 times larger than the non-enhanced promoters, the neuronal specificity was significantly decreased in most cases. However, the neuronal specificity of E/SYN hybrid promoter exhibited the least decrease only in the thalamus. Furthermore, the transcriptional activity and neuronal specificity of E/SYN promoter were sustained for up to 8 weeks. Thus, lentivirus with E/SYN promoter is the best vector for strong persistent expression in neurons.

Dioxin and fly ash free incineration by ash pelletization and reburning.

Dioxins (DXNs) in municipal waste incinerator fly ash were effectively reduced by pelletizing the mixture of ash, cement, and sodium phosphate and reburning the pellets in a laboratory scale bubbling fluidized bed (BFB) furnace. Three types of pellets--A, B and C, of various sizes and compositions were used in the experiments. The efficiency of DXN reduction in the pellet matrix was proportional to the incineration time, temperature, and degree of pellet incineration. At 700 degrees C and incineration time sufficient for a complete burnout, the efficiency of DXN reduction in the pellets of type A and C was found to be 99.9% and 99.7%, respectively. Correspondingly, the DXN concentration in the pellets decreased from 862 ng TEQ/kg to 0.9 ng TEQ/kg for pellets A and 2.2 ng TEQ/kg for pellets C. The residual concentration of coplanar polychlorinated biphenyls (coplanar PCBs) was below 0.2 ng TEQ/kg and 0.4 ng TEQ/kg, respectively. Assuming a tortuosity factor of tau = 3 and the reaction rate constants of 0.013 m/s (at 700 degrees C) and 0.025 m/s (at 800 degrees C), the experimental pellet incineration times were reasonably predicted by using the shrinking core model. Possible DXN evaporation from the pellets was also studied. The amount of DXNs in the flue gas captured by an impinger trap was less than 3% when the reactor was operated at 700 and 800 degrees C. The described method of fly ash pelletization and reburning seems to be a relatively easy and inexpensive way to reduce both the emission of DXNs and the amount of fly ash.

Increased apoptosis associated with depressed type of early intestinal gastric cancer.

Early gastric cancer can be macroscopically classified into elevated and depressed types. To clarify the relationship between macroscopic appearance of early gastric cancer and apoptosis or cell proliferation, formalin-fixed paraffin-embedded tissue specimens of 44 intestinal-type early gastric cancers were investigated by the TUNEL method and immunohistochemical techniques. Diffuse type was excluded in this study. When tissue sections of gastric cancer were vertically classified into the 3 compartments of luminar, intermediate and basal, the apoptosis index (%) was significantly higher in the basal compartment of depressed type (1.76 +/- 2.04, mean +/- SD) than in the basal compartment of elevated type (0.63 +/- 0.81, P = 0.01). In depressed type, the apoptosis index (%) was significantly higher in the basal compartment than in the luminar compartment (0.76 +/- 0.85, P = 0.03). Apoptosis-inducing protein, Bax, was expressed more in each of the compartments of depressed type than in those of elevated type, while there were no significant differences in expression of anti-apoptotic protein, Bcl-2, between the two types. Moreover, the apoptosis index (%) of Bax-positive gastric cancer was significantly higher in the basal compartment (P = 0.03), compared to that of Bax-negative gastric cancer, while there were no significant differences in apoptosis index (%) in any compartment between Bcl-2-positive and Bcl-2-negative gastric cancers. There were no significant differences in Ki-67 expression, either between the two types, or among the compartments of depressed type. These results indicate that increased apoptosis with excessive expression of Bax in the basal compartment is involved in the morphogenesis of the depressed type in intestinal-type early gastric cancer.

Changes in BDNF-immunoreactive structures in the hippocampal formation of the aged macaque monkey.

We investigated the changes of brain-derived neurotrophic factor (BDNF)-immunoreactive structures in the hippocampal formation of aged macaques (Macaca fuscata fuscata). At adult stages (10 and 12 years), BDNF immunoreactivity occurred in the neurons of the dentate gyrus, the pyramidal neurons in the CA1, CA2, CA3 subfields and the subiculum, and the neurons in the CA4 subfield and the entorhinal cortex. The apical dendrites were also BDNF immunopositive. In aged monkeys (26, 30 and 32 years), the intensity of the BDNF-immunoreactivity declined significantly in cell bodies and dendrites of the neurons in the hippocampal formation except the CA2 pyramidal neurons. These findings indicate that BDNF is one of the vulnerable signal molecules during the aging process of the primate hippocampal formation.

TrkB dimerization during development of the prefrontal cortex of the macaque.

To date, two subtypes of TrkB, a BDNF receptor, have been described. One is full-length TrkB (TK+), which has a tyrosine kinase-containing intracellular domain. The other is truncated TrkB (TK-), which has a short intracellular domain lacking the tyrosine kinase. In this study, we investigated the dimerization of TrkB subtypes in the developing monkey prefrontal cortex by means of cross-linking. At embryonic day 120, the TK+/TK+ and the 100 kDa/100 kDa homodimers were observed with BDNF stimulation. At the newborn stage, the TK+/TK+ and the TK-/TK- homodimers were observed with BDNF stimulation. At the adult stage, the TK-/TK- homodimer and the TK+/TK- heterodimer were formed by BDNF stimulation. The levels of all dimers increased in proportion to the concentration of BDNF. Moreover, the dimers were clearly formed within 5 min of treatment with BDNF. BDNF and NT-4/5 induced the dimers, whereas NT-3 formed slight dimers but NGF did not. Furthermore, anti-BDNF antibody inhibited the TrkB dimerization. Moreover, the intercellular binding proteins of TrkB were not cross-linked by BS3. Therefore, these results suggest that the change in dimerization among TrkB subtypes occurs during development of the monkey prefrontal cortex.

Marked and prompt hemodynamic improvement by carperitide in refractory congestive heart failure due to dilated cardiomyopathy.

A 16-year-old Japanese male diagnosed with congestive heart failure (CHF) due to dilated cardiomyopathy was treated by conventional intensive treatment such as intravenous infusion of diuretics, catecholamines, and phosphodiesterase inhibitors with vasodilators. However, he developed a low output syndrome with appearances of hyponatremia and hypochloremia. As a consequence, intravenous infusion of carperitide (synthetic atrial natriuretic peptide) was added to the therapy. Thereafter his symptoms and hemodynamic parameters promptly and dramatically improved without significant diuresis, and this amelioration persisted for more than 20 days without drug intolerance. This outcome suggests that use of carperitide may be a safe and efficacious means to reduce cardiac preload without hypotension and tachycardia in patients with refractory CHF in whom intensive treatment has already been performed.

A case of idiopathic constrictive bronchiolitis in a middle-aged male smoker.

When one sees a middle-aged male smoker who presents with progressive exertional dyspnoea and irreversible airflow obstruction, the most likely clinical diagnosis is pulmonary emphysema or chronic obstructive pulmonary disease (COPD). We report a 45-year-old male smoker who was initially suspected to have such a disease but was eventually diagnosed as having idiopathic constrictive bronchiolitis by lung biopsy, clinical history, and laboratory findings. A finding on lung computed tomography of diffuse hyperinflation but few low attenuation areas and relatively well-preserved diffusing capacity of carbon monoxide seems to be the key for suspecting this rare clinical entity. The pathological difference between this bronchiolitis and small airway disease observed in COPD will be also discussed.

[Helicobacter pylori infection and eradication].

H. pylori infection is associated with various gastroduodenal diseases such as gastritis, peptic ulcer, gastric cancer, gastric MALT lymphoma. H. pylori infection is suggested that it plays a role as protective factor not promoting factor for reflux esophagitis and GERD. Epidemiological studies showed lower prevalence of H. pylori infection in reflux esophagitis and Barrett's esophagus comparing the control. Increased occurrence of reflux esophagitis after curing of H. pylori infection was reported. However, the relationship between H. pylori infection and reflux esophagitis has not been actually made clear. Also the mechanism of reflux esophagitis occurrence after H. pylori eradication is not obscure.

Absence of TrkB and insulin receptor beta in the Triton insoluble low-density fraction (raft).

Cholesterol- and glycolipid-enriched microdomains within the plasma membrane of animal cells, including neurons, have been purified and used as a low-density membrane domain after extraction with Triton X-100 (raft), or after subcellular fractionation without detergent (LDM). In this study, we compared the protein compositions in the raft and the LDM. Membrane receptors, acylated- and glycosylphosphatidylinositol (GPI)- anchored proteins were enriched in the LDM. Further treatment of the LDM with Triton X-100 excluded the membrane receptors, TrkBs and insulin receptor beta. In the presence of calcium ions, the endogenous tyrosine kinase activities in the LDM and the raft were enhanced, suggesting an important role of calcium ions in the signal transduction via the LDM and the raft.

Development of full-length Trk B-immunoreactive structures in the hippocampal formation of the macaque monkey.

Distribution and morphological changes of cells containing the signal transducing neurotrophin receptor, full-length Trk B (fl-Trk B), were investigated in the hippocampal formation of the macaque monkey between embryonic day 140 and the adult stage. Western blot analysis showed that one main protein band, which migrated at 141 kDa, was detected in both the embryonic and adult hippocampal formation. In the pyramidal cells in CA1 and CA3 subfields, the subiculum, and the entorhinal cortex, fl-Trk B-immunoreactive dendrites were observable in the embryonic stage. In contrast, in the granule cells of the dentate gyrus, few dendrites were immunoreactive during embryonic and early developmental stages. This difference may be due to the later growth of the granule cells of the dentate gyrus. The existence of fl-Trk B immunoreactivity in the cell body and dendrites in the embryonic hippocampal neurons, suggests that BDNF and/or NT4/5 act on the hippocampal cells by autocrine/paracrine mechanisms. In the entorhinal cortex, fl-Trk B immunoreactivity became localized in the stellate cells in layer II and the pyramidal cells in layers III, V and VI in adulthood. This indicates that BDNF and/or NT4/5 are important for the maintenance of the projection neurons in the entorhinal cortex at the adult stage. The strongest fl-Trk B immunoreactivity in the hippocampal neurons occurred at postnatal month 4, corresponding to the period of greatest synapse production in the monkey hippocampus, suggesting that BDNF and/or NT4/5 with fl-Trk B may play a role in synapse formation in the monkey hippocampus.

Change of expression of full-length and truncated TrkBs in the developing monkey central nervous system.

We examined the expression of full-length TrkB (TrkBTK+) and truncated TrkB (TrkBTK-) in the central nervous system (CNS) of the macaque monkey (Macaca fascicularis) using a western blot analysis. At the adult stage, the levels of TrkBTK+ in cerebral cortices were higher than those in other structures of CNS and the expressions of TrkBTK+ in the association cortices (except area PE) were relatively lower than those in the primary cortices. In contrast, TrkBTK- in the hippocampus and the cerebellum was significantly higher than in other structures. In various developing cerebral cortices, TrkBTK+ was detected at the same levels from embryonic day 120 (E120) to the adult period. In contrast, the expression of TrkBTK- increased remarkably after the newborn stage (NB), reached the maximum level at postnatal day 60 (P60) and maintained the same level into adulthood. The peaks of TrkBTK- in the association cortices were more delayed than in the primary cortices. The expression of TrkBTK- occurred at a time that correlates with the elimination of axons and the down-regulation of neuropeptides. The present study suggests that TrkBTK- plays an important role in the axonal remodelling and that it may act as a negative effector of TrkBTK+ in the primate CNS, reducing responsiveness to BDNF and/or NT-4/5.

[Changes of 24-h Holter monitor recordings in association with interferon alpha therapy for chronic hepatitis C].

We examined cardiovascular complication of interferon (IFN) therapy in 23 patients with chronic hepatitis C who did not have cardiac disease prospectively. Twenty four-h Holter monitor recordings were performed before and during IFN therapy. Seven of these patients (30%) showed abnormalities on their 24-h Holter monitoring recordings. Premature ventricular contraction (PVC) occurred in two patients, intermittent WPW syndrome in one, and ST-T change in four. Only one patient with PVC complained of palpitation. These complications were not severe and immediately after IFN therapy was stopped. There was no correlation between Holter ECG abnormalities and sex, age, quantity of HCV, or 2-5 oligoadenylate synthetase activity. It was suggested that cardiovascular complications caused by IFN therapy occurred more frequently than expected. However, diagnosis of these complications is difficult because most patients have no subjective symptoms and there is scarcely any change in laboratory test results. Careful observation of patients may be required during IFN therapy regardless of cardiovascular symptoms.

The use of the block cycle length as a safe and efficient means of interrupting sustained ventricular tachycardia and its pharmacological modification.

In nine patients who had inducible monomorphic sustained ventricular tachycardia (VT), rapid pacing was performed in 11 episodes of morphologically distinct VT at progressively shorter cycle lengths and VT was interrupted at a critical cycle length. The VT interrupting critical cycle length was defined as the block cycle length (BCL) and the effect of Class I antiarrhythmic drugs were examined. Both the VT cycle length (VTCL) and the BCL were prolonged after administration of either drug. The overall mean ratio of the BCL to the VTCL was unchanged after procainamide administration, but increased after the use of mexiletine. The ratio, however, varied in individual VTs and the BCL after treatment with Class I antiarrhythmic drugs could not be predicted from the ratio baseline value, although the ratio was always > 60% and the hazard of VT acceleration might be avoided if the BCL is used.

Use-dependent electrophysiologic effects of DL-sotalol and modulation by isoproterenol in the human ventricle.

The interaction between dl-sotalol and isoproterenol on the ventricular effective refractory period (VERP) and conduction were examined in an electrophysiologic study of 9 patients at drug-free baseline, after 14 days of dl-sotalol administration (320 mg/day), and after the administration of isoproterenol. In all 9 patients, ventricular tachyarrhythmia could not be induced after dl-sotalol treatment. Isoproterenol was administered as a loading dosage of 0.025 microgram/kg for 5 min with a maintenance dosage of 0.0025 microgram/kg/min. The VERP and the QRS duration were determined at paced cycle lengths of 600, 400 and 300 msec. DL-sotalol and dl-sotalol + isoproterenol had no effect on ventricular conduction at the three cycle lengths. The VERP was significantly prolonged after dl-sotalol treatment at paced cycle lengths of 600 (241 +/- 16 to 302 +/- 28 msec, p < 0.001), 400 (223 +/- 21 to 280 +/- 23 msec, p < 0.001) and 300 msec (202 +/- 16 to 256 +/- 24 msec, p < 0.005), but there was a parallel shift of the VERP, suggesting the absence of use-dependent effects on the VERP. The dl-sotalol-induced VERP prolongation was partially reversed by isoproterenol, but it remained significantly prolonged above baseline values at paced cycle lengths of 600 (241 +/- 16 to 281 +/- 18 msec, p < 0.01), 400 (223 +/- 21 to 258 +/- 20 msec, p < 0.01) and 300 msec (202 +/- 16 to 247 +/- 22 msec, p < 0.01). The shortening of the VERP was greater at longer basic cycle lengths (600 and 400 msec) than at the shorter paced cycle length (300 msec, p < .05), but the percentage increase of the VERP was similar at the three basic cycle lengths of 600 (16%), 400 (15%) and 300 (20%) msec, indicating the lack of reverse use-dependency. The absence of reverse use-dependency of dl-sotalol on the VERP, even after isoproterenol administration, may be beneficial in the therapy of ventricular tachyarrhythmias and may account in part for the high efficacy of this drug.

The usefulness of Holter monitoring in selecting pharmacologic therapy for patients with sustained monomorphic ventricular tachycardia: studies in patients in whom no effective pharmacologic therapy could be determined by electrophysiologic study.

The usefulness of Holter monitoring (HM) in selecting pharmacologic therapy for patients with sustained monomorphic ventricular tachycardia (VT) was evaluated in patients in whom no effective pharmacologic therapy could be determined in an electrophysiologic study (EPS). The study population consisted of 49 consecutive patients with sustained VT who were receiving long-term pharmacologic therapy despite the fact that no pharmacologic therapy had been found to be effective in the EPS. The efficacy of the pharmacologic therapies was assessed by HM. A reduction in frequent (10/h) premature ventricular contractions (PVCs) was used as an index of treatment efficacy, with therapies achieving substantial PVC suppression (>70% of all PVCs) being considered to be effective (HM effective group). When no therapy was found to be effective when assessed by HM, a drug with any other beneficial effect, eg, reduction in VT rate, was chosen (HM ineffective group). VT recurrence and survival were compared between groups. During the follow-up period of 31+/-28 months, VT recurrence was observed in a total of 25/49 patients: 3/17 patients in the HM effective group, in 18/25 in the HM ineffective group, and in 4/7 in the HM undetermined group (p=0.0487). Sudden cardiac death occurred in a total 7/49 patients: 2/17 patients in the HM effective group, 4/25 patients in the HM ineffective group, and 1/7 patient in the HM undetermined group (p=0.2828). Among patients in whom no effective therapy could be determined by EPS, the VT recurrence rate was significantly lower in the group in whom treatment was effective as assessed by HM than among those in whom treatment was assessed by HM to be ineffective. Sudden cardiac death rate was also lowest in the HM effective group, although the difference was not statistically significant. HM assessment was considered useful in selection of pharmacologic therapy for patients in whom no effective therapy could be determined in the EPS.