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Objectives: Although acute anterior cruciate ligament reconstruction (ACLR) is often avoided because of postoperative joint stiffness, delayed ACLR can lead to a longer recovery time and can have a negative impact on physical function due to detraining. This study aimed to determine the effects of acute ACLR on postoperative outcomes, including muscle strength, performance, and return to sports. Methods: A total of 110 patients who underwent anatomical ACLR using hamstring autografts were included in this study and were divided into three groups: acute (ACLR performed within 2 weeks after ACL injury), 2–6 weeks (ACLR performed between 2 and 6 weeks after injury), and 6–12 weeks (ACLR performed between 6 and 12 weeks after injury). Several parameters were evaluated, including range of motion, knee joint stability, isokinetic knee strength, performance, and return to sports. Results: No significant differences were found in the range of motion or knee joint stability between the groups. The acute group exhibited significantly greater quadriceps strength at 3 months postoperatively than the other groups (p < 0.05). The single-leg hop test showed that 66.7%, 38.7%, and 33.3% of the patients in the acute, 2–6 weeks, and 6–12 weeks groups, respectively, recovered to an LSI of 90% or greater (p = 0.09, Cramer's V = 0.27). All patients in the acute group were able to return to sports (p = 0.14; Cramer's V = 0.28). Conclusions: Acute ACLR is advantageous for the early recovery of strength and performance without adverse events. Acute ACLR may shorten the time spent away from sports activities. [ABSTRACT FROM AUTHOR]

Background: An increased perioperative complication rate has been a concern with one-stage bilateral total knee arthroplasty (TKA). The purpose of this study was to retrospectively investigate the perioperative safety and clinical results of one-stage bilateral TKA in selected low-risk patients. Methods: Sixty-seven patients who received one-stage bilateral TKAs for osteoarthritis who were American Society of Anesthesiology (ASA) class 1 or 2 were included in this study. Perioperative complications, blood loss, transfusion rate, blood laboratory results, and clinical results were evaluated up to 1 year after surgery. Results: No major complications (deep infection, pulmonary embolism, cerebrovascular accident, myocardial infarction, death, or removal or revision of the implants) were observed. The average total blood loss was 1139.5 ml. The transfusion rate was 95.5%. Postoperative hemoglobin level and C-reactive protein level gradually improved up to postoperative day 21 (P < 0.01). Bilateral knee extension knee angles and clinical scores improved postoperatively as compared with preoperative values (P <0.01). Conclusions: Although total blood loss and transfusion rate can be high, this preliminary case series suggested that the one-stage bilateral TKA in ASA class 1 or 2 patients can have high perioperative safety levels, and good clinical results can be obtained up to 1 year after surgery. If low-risk patients are selected for bilateral TKA, a one-stage procedure can be beneficial for patients, with a minimal increase in the risk of complications. [ABSTRACT FROM AUTHOR]

The crack-free metal-organic chemical vapor deposition (MOCVD) grown AlGaN/ GaN heterostructures on Si substrate with modified growth conditions of AlN nucleation layer (NL) and its influence on the electrical and structural properties of conductive GaN layer are presented. From the Hall electrical measurements, a gradual decrease of two-dimensional electron gas (2DEG) concentration near heterointerface as the function of NL thickness is observed possibly due to the reduction in difference of piezoelectric polarization charge densities between AlGaN and GaN layers. It also indicates that the minimum tensile stress and a relatively less total dislocation density for high pressure grown NL can ensure a 20 % increment in mobility at room temperature irrespective of the interface roughness. The thickness and pressure variations in NL and the subsequent changes in growth mode of AlN contributing to the post growth residual tensile stress are investigated using X-ray diffraction and Raman scattering experiments, respectively. The post growth intrinsic residual stress in top layers of heterostructures arises from lattice mismatches, NL parameters and defect densities in GaN. Hence, efforts to reduce the intrinsic residual stress in current conducting GaN layer give an opportunity to further improve the electrical characteristics of AlGaN/GaN device structures on Si. [ABSTRACT FROM AUTHOR]

Abstract: A human anterior cruciate ligament (ACL) is composed of an anteromedial (AM) and posterolateral (PL) bundle which have different biomechanical functions. ACL degeneration and ACL deficiency often occur in patients with osteoarthritis (OA); however, histological evaluation of each bundle of the ACL in the OA knee has not been reported. Our objective was to compare the degenerative changes of the AM and PL bundle in the OA knee based on histological appearance. A histological evaluation of the AM and PL bundle from 49 varus OA knees was performed. Fifty-three percent of the AM bundle and 78% of the PL bundle showed severe histological degenerative changes. The degenerative changes were statistically more severe in the PL bundles than the AM bundles (p <0.05). Since the cross sectional area of the AM bundle is larger than that of the PL bundle and the pattern of length change of the PL bundle is greater than that of the AM bundle, it would logically follow that the PL bundle would show more severe degenerative changes than the AM bundle. This study identified the histological appearance of the bundles of the ACL of the OA knee and may help to elucidate the process of ACL degeneration in the OA knee. [ABSTRACT FROM AUTHOR]

Abstract: Anpirtoline has been described as an agonist at 5-HT1B receptors with a relatively high potency. It also acts as an agonist at 5-HT1A receptors, but has a lower potency than at the 5-HT1B sites. There is very little known about the mechanism by which anpirtoline influences regional 5-HT synthesis. The aim of the present study was to investigate the effects of acutely and chronically administered anpirtoline on 5-HT synthesis in the rat brain using the autoradiographic α-[14C]methyl-l-tryptophan method. In the acute study, anpirtoline (2.0 mg/kg) was administered intraperitoneally 30 min before the tracer injection. The control rats were injected with the same volume of saline. In the chronic study, anpirtoline (2 mg/kg per day) was injected subcutaneously in saline once a day for 10 days. There were no significant differences between the plasma-free and total tryptophan concentrations between the anpirtoline treatment and the respective control groups. In the acute experiment, 5-HT synthesis rates in all of the brain areas investigated were significantly decreased by anpirtoline when compared to the saline-treated group. In the chronic anpirtoline experiment, 5-HT synthesis rates of almost all of the projection areas, as well as the raphe nuclei, were normalized or had a tendency to be normalized. These results suggest that it is likely that the terminal 5-HT1B receptors are involved in the regulation of 5-HT synthesis in the projection areas and that 5-HT synthesis, in the raphe, is likely influenced by anpirtoline''s 5-HT1A and/or 5-HT1B agonistic properties. [Copyright &y& Elsevier]

Abstract: The effects of chronic buspirone treatments, administered by minipump at doses of 10 and 20mg/(kgday) for 14 days, on brain 5-HT synthesis in olfactory bulbectomized (OBX) rats were evaluated. The α-[14C]methyl-l-tryptophan autoradiographic method was used. We compared the synthesis in the buspirone treated OBX rats (administered either 10mg/(kgday) (OBX-10) or 20mg/(kgday) (OBX-20)) to that of the saline treated OBX rats (OBX-SAL), and the sham operated rats (SHX) treated with saline. In addition, OBX-10 rats were compared to SHX rats treated with 10mg/(kgday) (SHX-10) of buspirone. All treatments were carried out for 14 days. Adult Sprague–Dawley rats were used. Two weeks following the OBX or SHX procedures, the rats were assigned to the OBX-10, OBX-20, OBX-SAL, SHX-10, or SHX-SAL groups, respectively. The 5-HT synthesis rates R (pmol/(g/min)) were calculated from the trapping constant of α-[14C]MTrp (K*; ml/(gmin)) and the plasma concentration of the plasma non-protein-bound tryptophan (Cp; pmol/ml) using the lumped constant (LC) measured previously in the rat brain. There was no significant difference in the plasma free or total tryptophan among these groups. The overall synthesis in the OBX-10 group was not statistically different from the OBX-SAL group, but it was different from the OBX-20 and SHX-SAL groups. The OBX-20 rats had an overall significant reduction in 5-HT synthesis, when compared to the OBX-SAL group, but did not differ from the SHX-SAL group, which did not differ from the SHX-10 group. These results suggest that 10mg/(kgday) of buspirone for 14 days in the OBX rats did not produce a significant alteration in 5-HT synthesis, but 20mg/(kgday) for 14 days resulted in an overall significant reduction in brain 5-HT synthesis. The latter treatment brought the synthesis to the level found in the sham operated rats, i.e., a normal level. These results suggest that normalization (reduction to the level found in the SHX-SAL rats) of 5-HT synthesis in the OBX requires a greater dose of buspirone (20mg/(kgday)) than that needed to produce a desensitization of the 5-HT1A receptors in the sham operated rats (10mg/(kgday)). This probably indicates that 5-HT1A receptors have different functionality in the OBX rats than that found in the intact or sham operated rats. Furthermore, our results support the hypothesis that 5-HT1A receptors mediate the antidepressant-like effect of 5-HT1A agonists, as the chronic 5-HT1A agonist treatment in the depression model known to be sensitive to antidepressants resulted in the normalization of 5-HT synthesis. [Copyright &y& Elsevier]

Presents a study that analyzed the effects of chronic administration of citalpram on serotonin synthesis rates. Evaluation of serotonin synthesis using an autoradiographic method; Results; Conclusions.

Abstract: The effects of acute and chronic administration of the serotonin (5-HT)1B agonist CP-93,129, on 5-HT synthesis rates were evaluated using the α-[14C]methyl-l-tryptophan (α-MTrp) autoradiographic method. In the acute treatment study, CP-93,129 (7mg/kg) was injected intraperitoneally 30min before the α-MTrp injection (30μCi over 2min). A single dose of CP-93,129 caused a significant increase in the synthesis in the median raphe nucleus (MR) without a significant influence on the dorsal raphe nucleus (DR). There was a reduction in 5-HT synthesis in almost all of the projection areas. In the chronic treatment study, CP-93,129 was administered continuously (7mg/kg/day) for 14 days using an osmotic minipump implanted subcutaneously. The chronic treatment with CP-93,129 did not produce a significant change in 5-HT synthesis in the raphe nuclei nor in the nerve terminal structures, except for the medial frontal bundle and the visual and sensory-motor cortices. The unaltered 5-HT synthesis rates in the chronic treatment study probably reflect a normalization of the synthesis as a result of the desensitization of 5-HT1B autoreceptors and/or heteroreceptors. [Copyright &y& Elsevier]

Abstract Serotonin synthesis rates were evaluated using α-[[sup 14]C]methyl- l-tryptophan (α-MTrp) autoradiographic methods in olfactory bulbectomized (OBX) rats. They were significantly (p < 0.05) increased in the frontal (50%) and parietal (40%) cortices, superior olive (over 30%), and the substantia nigra (30%) in the OBX rats as compared to the sham operated animals. There were also increases in 5-hydroxytryptamine (5-HT) synthesis in some limbic areas: the cingulate (32%), the medial forebrain bundle (58%), the hippocampus (13–25%) and the thalamus (22–40%). The largest increase in 5-HT synthesis after OBX was observed in the sensory-motor cortex (67%). 5-HT synthesis rates were significantly decreased in the dorsal and medial raphe nuclei, but there was no significant change the ventral tegmental area and the locus coeruleus following OBX. These results indicate that olfactory bulbectomy causes an imbalance in 5-HT synthesis in some projection areas by disproportionally increasing 5-HT synthesis rates in specific brain regions and making more 5-HT available for neurotransmission. This imbalance in 5-HT synthesis and the subsequent elevation of tissue 5-HT may be responsible for the creation of non-physiological circuitry which may, in part, be reflected in the symptoms resembling human depression. [ABSTRACT FROM AUTHOR]

We have investigated the regions around deep-pits and their limitations on the performance of metal-organic chemical vapor deposition grown AlGaN/GaN high-electron-mobility transistors (HEMTs) on Si. The device characteristics such as maximum drain current density (IDSmax), threshold voltage (Vth), and three terminal-OFF breakdown (BVOFF) of a HEMT were affected based on the distance of deep-pits from a device active region. The deterioration of HEMT characteristics are significant if the active region is present within 50 μm radius of a deep-pit and becomes insignificant for distance beyond 50 μm. These device characteristics were compared with optical measurements and it was found the region around 50 μm radius of a pit have large dislocations and defects as confirmed by cathodoluminescence. Further, the E2 Raman shift measurements reveal additional stress in the 50 μm region around a pit. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, activates Toll-like receptors (TLRs). Porphyromonas gingivalis (Pg) may be involved in the progression of periodontal disease. Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived from Escherichia coli (Ec-LPS). However, whether Pg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects of Pg-LPS. For comparison, effects of Ec-LPS were also studied. We additionally investigated the influence of systemic administration of Pg-LPS or Ec-LPS on IL-6, TNF-alpha, and IL-10 levels in blood, as they could be involved in the changes in locomotion. The TLR4 receptor antagonist TAK-242 was used to study the involvement of TLR4. Since Pg-LPS may block TLR4 in vitro, we analysed the effects of Pg-LPS on Ec-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Pg- or Ec-LPS and TAK-242 were administered intraperitoneally. Ec-LPS (840 μg/kg), but not Pg-LPS (100, 500 and 840 μg/kg), inhibited novelty-induced locomotion, which was antagonized by TAK-242 (3.0 mg/kg). Ec-LPS (840 μg/kg) increased blood levels of IL-6 and IL-10, which were antagonized by TAK-242 (3.0 mg/kg). However, TAK-242 did not inhibit Ec-LPS-induced increases in TNF-alpha levels in blood. Pg-LPS (100, 500, and 840 μg/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. The Ec-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited by Pg-LPS (500 μg/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration of Ec-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast, Pg-LPS did not exhibit these effects. The present study also provides in vivo evidence that Pg-LPS can inhibit TLR4-mediated increases in blood levels of IL-10, a cytokine thought to prevent the development of periodontal disease. [ABSTRACT FROM AUTHOR]

Dislocation reaction in a GaN layer grown on 4-in. Si(111) with AlGaN/AlN strained layer superlattice was observed by transmission electron microscopy. The reaction between a dislocation ( b =1/3[ 1 2 ¯ 10 ]) and another dislocation ( b =1/3[ 11 2 ¯ 0 ]) to form a dislocation segment ( b =1/3[ 2 1 ¯ 1 ¯ 0 ]) was demonstrated by plan-view observation using weak-beam dark-field and large-angle convergent-beam electron diffraction methods. Observed reaction occurred with dislocation motion after dislocation propagation with epitaxial growth. [ABSTRACT FROM AUTHOR]

The article presents author's comments on advantages of endoscope used in microsurgery as aneurysmal clipping and microvascular decompression.

Abstract: The role of 3C-SiC intermediate layers in III-nitride crystal growth has been studied by observing III-nitride epilayers grown on Si substrates. We found that better quality epilayers were obtained by using such intermediate layers than by direct growth on Si substrates. In the case of III-nitride epilayers grown directly on Si, the layers grown at the initial stage are not flat. High-resolution transmission electron microscopy observations showed that a non-crystalline layer exists at the interface between the AlN layer and the Si substrate. Thus, the initial growth of III-nitride becomes disordered. On the other hand, the interface between 3C-SiC and the AlN layer is atomically flat, and there is no non-crystalline layer present. We concluded that III-nitride epilayers on Si substrates with 3C-SiC intermediate layers are promising for the fabrication of vertical devices. [Copyright &y& Elsevier]

Abstract: The olfactory bulbectomized (OBX) rat is considered to be a good model of the pathology of human depression and also of the functional actions of antidepressant drug therapy. It has been proposed that antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) can be accelerated by blocking 5-HT1A/B autoreceptors with pindolol. The underlying mechanism is thought to involve acute unrestricting of 5-HT release and, consequently, relatively enhanced 5-HT turnover throughout the forebrain serotonergic networks. The effect of this combination on 5-HT turnover in sham operated or OBX rats can be assessed at the level of 5-HT synthesis, a very important presynaptic step in serotonergic neurotransmission, using the α-[14C]methyl-l-tryptophan autoradiography method. In sham rats, acute citalopram (20mg/kg) treatment increased synthesis at almost all serotonergic terminal regions but slightly decreased synthesis at serotonergic cell body regions (i.e. dorsal and median (not significant) raphe; ∼16%). Combining pindolol (10mg/kg) with citalopram further increased synthesis at many regions in sham rats (relative to treatment with only citalopram). In OBX rats, citalopram decreased synthesis at a few terminal regions and greatly decreased synthesis at the dorsal and median raphe (∼45%; relative to OBX rats treated with saline). Combining pindolol with citalopram greatly increased synthesis at almost all regions in OBX rats (relative to treatment with only citalopram). These results suggest that acute citalopram effects result in elevated terminal 5-HT synthesis, but these effects are restrained by 5-HT1A/B autoreceptor feedback to different degrees in sham and OBX rats. Moreover, 5-HT1A/B autoreceptor feedback is stronger in OBX rats and may underlie the delay of SSRI effects in OBX rats and, correspondingly, in human depression. Pindolol acceleration and augmentation of SSRI antidepressant therapy for human depression may be mediated by attenuation of 5-HT1A/B autoreceptor feedback, permitting unhindered SSRI effects on serotonergic terminals. [Copyright &y& Elsevier]

The diagnosis of tethered cord syndrome (TCS) without typical conus medullaris symptoms and the radiological features such as a low set conus medullaris or dysraphic malformation is difficult. We report 11 year old identical twin brothers with TCS associated with the conus at the normal level. Their presenting symptom was progressive leg pain and both patients underwent surgical interruption of the filum terminale. The pain recurred in one patient treated surgically only after symptom became worse but resolved immediately in the other sibling treated promptly. We indicate the importance of early diagnosis and treatment of TCS to obtain excellent long-term outcome despite the absence of a low set conus or specific symptoms. Furthermore, when a twin or sibling of an affected person has neurological symptoms and the cutaneous signature of spinal dysraphism, radiological examination should be performed to establish the cause. [ABSTRACT FROM AUTHOR]

Abstract: Alterations of serotonin (5-HT) levels and serotonergic transmission have been associated with depression. 5-HT synthesis is an important factor of serotonergic neurotransmission that may also be altered in depression. Many studies of the relationships between brain serotonergic functions and affective disorders have been performed in different animal models. In this study, brain regional 5-HT synthesis was examined using the α-[14C]methyl-l-tryptophan (α-MTrp) autoradiographic method in a genetic rat model of depression, Flinders Sensitive Line (FSL) rats, and was compared to both the Flinders Resistant Line (FRL) rats and the control Sprague–Dawley (SD) rats. The plasma concentration of free tryptophan in the FSL rats was not significantly different (p >0.05; ANOVA and post-hoc Bonferroni correction) when compared to that of the FRL and SD rats. The FSL rats had significantly lower 5-HT synthesis (one sample two-tailed t-test on the ratio) than both the FRL and SD rats (the mean ratios were 0.78±0.12 and 0.73±0.15, respectively). Overall, the 5-HT synthesis in the FRL rats was not significantly different (p >0.05) from that in the SD rats (one sample two-tailed t-test on the ratio and the mean ratio was 0.93±0.13). Studies of individual brain structures, such as the raphe nuclei and their many terminal areas, including the nucleus accumbens, cingulate and frontal cortex, hippocampus, amygdala, and thalamus revealed significant reductions (typically 25–50%) in 5-HT synthesis in the FSL rats compared to the non-depressive FRL and SD rats. These results suggest that significantly reduced 5-HT synthesis in the raphe nuclei and limbic areas in FSL rats may contribute to their depressive features. [Copyright &y& Elsevier]

Objective.—We investigated the value of the jugular compression test (JCT) in screening patients with chronic headache attributable to persistent cerebrospinal fluid (CSF) leakage. Methods.—Clinical records of 35 consecutive patients who underwent both 111In-diethylenetriamine pentaacetic acid radioisotope (RI) cisternography and JCT were retrospectively analyzed. Results.—A strong correlation was seen between JCT and RI cisternographic findings. Most patients who reported a feeling of fullness in the ear, hearing loss or headache during JCT had positive findings on RI cisternograms indicative of CSF leakage. In contrast, no RI study abnormalities were seen in patients reporting no symptoms in JCT. Conclusions.—Among patients complaining of refractory headache and other miscellaneous symptoms, JCT may represent a simple, economic, and reliable technique in the screening of candidates for RI cisternography to evaluate CSF leakage. A subgroup of patients with chronic headache may have persistent CSF leakage. [ABSTRACT FROM AUTHOR]

Background: Ploidy is a highly significant prognostic factor for pediatric acute lymphoblastic leukemia (ALL). Children with hypodiploid ALL have poor outcomes despite current intensive chemotherapy. Little has been investigated with regard to hypodiploid ALL in Japanese children. Methods: We retrospectively collected clinical data on hypodiploid ALL cases from the registries of prospective multicenter trials conducted by the four independent clinical study groups in Japan between 1997 and 2012. Results: A total of 117 ALL patients with hypodiploidy were analyzed in this study. There were 101, eight, and eight patients with 45, 44, and fewer than 44 chromosomes, respectively. The 5 year overall survival rates differed significantly: 86.0%, 87.5%, and 62.5% for patients with 45, 44, and fewer than 44 chromosomes, respectively (P = 0.037). Of the eight patients with 44 chromosomes, seven were alive, including five patients who maintained complete remission without undergoing hematopoietic stem cell transplantation (HSCT). Of the eight patients with fewer than 44 chromosomes, six were good responders to prednisolone and none had induction failure, but the relapse rate was high (5/8). No patients had central nervous system relapse. Four patients underwent HSCT after relapse, but only one survived. Conclusions: Outcomes of Japanese ALL patients with fewer than 44 chromosomes were poor, as previously reported in other countries. Although the sample size was small, patients with 44 chromosomes had better prognoses than those previously reported. Further studies including international collaboration are needed to improve outcomes for pediatric ALL patients with fewer than 44 chromosomes. [ABSTRACT FROM AUTHOR]

This study reviewed the clinical characteristics of 112 pediatric B-cell precursor acute lymphoblastic leukemia ( BCP- ALL) patients with TCF3- PBX1 fusion treated according to the Japan Association of Childhood Leukemia Study ( JACLS) ALL02 protocol ( n = 82) and Children's Cancer and Leukemia Study Group ( CCLSG) ALL 2004 protocol ( n = 30). The 3-year event-free survival ( EFS) and overall survival ( OS) rates were 85.4 ± 3.9% and 89.0 ± 3.5% in JACLS cohort, and the 5-year EFS and OS were 82.8 ± 7.0% and 86.3 ± 6.4% in CCLSG cohort, respectively, which are comparable to those reported in western countries. Conventional prognostic factors such as age at onset, initial white blood cell count, and National Cancer Institute risk have also no impact on OS in both cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients, was unique: eight of nine patients relapsed during the maintenance phase and one patient had primary induction failure. However, bone marrow status and assessment of minimal residual disease on days 15 and 33 did not identify those patients. Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS cohort, as did one patient in CCLSG cohort. International collaborative study of larger cohort is warranted to clarify the impact of the IKZF1 deletion on the poor outcome of TCF3- PBX1 positive BCP- ALL. [ABSTRACT FROM AUTHOR]

Abstract: Previously, we successfully applied a new method composed of drilling, bone marrow transplantation (BMT), external fixation and low-intensity pulsed ultrasound (LIPUS) for the clinical treatment of Kienböck’s disease. The purpose of this study was to investigate whether bone regeneration can be induced by LIPUS and/or multiple drilling and/or BMT within a severely necrotic small-bone rabbit model. Eighteen rabbits were divided into three groups (BMT, drilling and control) and LIPUS stimulation was introduced daily for 8 weeks post-transplantation. Next, 12 additional rabbits were produced for the BMT group and LIPUS stimulation was introduced daily for 4 and 12 weeks (n = 6 for each). Histopathologically, new bone formations were rarely observed in the drilling and control groups. In the BMT group, the mineralizing surface areas of LIPUS(+) showed a significant increase compared with LIPUS(−) for 8 weeks. LIPUS treatment alone did not accelerate the revitalization of necrotic bones. However, LIPUS combined with BMT tended to promote new bone formation. [Copyright &y& Elsevier]

The purpose of this study was to clarify the effect of gradual weight bearing (GWB) on regenerating cartilage. We developed a novel external fixation device (EFD) with a controllable weight-bearing system and continuous passive motion (CPM). A full-thickness defect was created by resection of the entire articular surface of the tibial plateau after the EFD was fixed in the rabbit's left knee. In the GWB group ( n = 6), GWB was started 6 weeks after surgery. In the CPM group ( n = 6), CPM with EFD was applied in the same manner without GWB. The control group ( n = 5) received only joint distraction. All rabbits were sacrificed 9 weeks after surgery. The central one-third of the regenerated tissue was assessed and scored blindly using a grading scale modified from the International Cartilage Repair Society visual histological assessment scale. The areas stained by Safranin-O and type II collagen antibody were measured, and the percentage of each area was calculated. There was no significant difference in the histological assessment scale among the groups. The percentage of the type II collagen-positive area was significantly larger in the GWB group than in the CPM group. The present study suggests that optimal mechanical stress, such as GWB, may affect regeneration of cartilage, in vivo. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:600-606, 2010 [ABSTRACT FROM AUTHOR]

Although treating Kienböck disease is controversial, we previously applied a new method that was less invasive and comprised drilling, bone marrow (BM) transplantation, external fixation, and radiating low-intensity pulsed ultrasound. We reported good clinical results obtained by this new method, which were comparable to those obtained using other, rather invasive methods. Here, we investigated the effect of drilling holes and transplanting BM into necrotic bone in an animal model to further understand the effect of these methods on the revitalization of necrotic bone. We used rabbit fourth tarsal bones, whose surfaces consist of cartilage and cortical bone, mimicking human lunate bone. We soaked the retrieved bones in liquid nitrogen to induce necrosis. After thawing, we inserted them separately into bilateral subcutaneous pouches in the backs of rabbits. A total of 60 rabbits were divided into four groups of 15 rabbits each: BM transplantation (BM group); peripheral blood transplantation (PB group); drilling (D group); control (C group). We sacrificed three rabbits to obtain six specimens in each group at 2, 4, 8, 12, and 20 weeks after operation and evaluated the specimens histomorphologically. In the BM group, significantly larger mineralizing surfaces, osteoblast surfaces, and osteoclast numbers were observed at 4, 8, and 12 weeks compared with those in the other groups. No significant differences were observed at 2 and 20 weeks in the groups except the mineralizing surface of the 20-week-BM group, which was significantly greater. We examined the efficacy of drilling and of BM transplantation for regenerating necrotic bone in a rabbit model. Our experiments suggest that drilling with BM transplantation to the necrotic bone accelerates bone formation and remodeling. [ABSTRACT FROM AUTHOR]

Abstract: The main objective of this investigation was to evaluate the effects of buspirone, a 5-HT1A agonist with some partial agonist properties and also an antidepressant, on regional 5-HT synthesis in Flinders Sensitive Line (FSL) rats (“depressed”), and to compare the effects to the Flinders Resistant Line (FRL) control rats (not “depressed”). In addition results were compared to those previously reported in normal Sprague–Dawley (SPD) rats (normal control). Serotonin synthesis in both FSL and FRL rats was measured following acute and chronic treatments with buspirone. Both of these strains were derived from the SPD rats. No direct comparison was done between the FSL saline and FRL saline groups, or the FSL buspirone and FRL buspirone groups, because the objective of the studies was to evaluate effects of buspirone in these two strains. The results show that acute treatment with buspirone elevates 5-HT synthesis throughout the brain in the FRL rats. In the FSL rats, there were reductions in some brain regions (e.g., dorsal and median raphe, amygdala, anterior olfactory nucleus, substantia nigra reticulate), while in other regions, there were increases in the synthesis observed (e.g., frontal, parietal, visual and somatosensory cortices, ventral hippocampus). In 20 out of the 30 brain regions investigated in the FSL rats, there was no significant change in the synthesis following acute buspirone treatment. During the chronic treatment, buspirone produced a significant reduction of 5-HT synthesis in 15 out of 30 brain regions in the FRL rats. In the FSL rats, buspirone produced a significant elevation of the synthesis in 10 out of 30 brain regions. In both the FSL and FRL rats, buspirone produced rather different effects than those reported previously for SPD (normal) rats. The acute effect in the FSL rats was somewhat similar to the effect reported previously for the SPD rats, while in the FRL rats, the acute buspirone treatment produced an effect observed previously in treatments with 5-HT1A antagonists suggesting an action of buspirone as partial agonist in FRL rats. The data suggest that with respect to 5-HT synthesis, FRL rats differ from SPD rats (a natural control; normal rats) and, as such, indicate that when the effects related to the serotonergic system (e.g., influence of serotonergic drugs) are studied in the FSL rats and compared to those in the FRL rats, any conclusions drawn may not reflect differences relative to a normal rat. [Copyright &y& Elsevier]

Abstract: Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) released from nerve terminals in the brain are primarily removed from the synaptic cleft by a reuptake mechanism. In part, the homeostasis is maintained by monoamine oxidase (MAO) deamination achieved primarily intracellularly. The present study''s aim was to examine the effect of the acute administration of the MAO inhibitors, moclobemide (a MAO-A inhibitor) and deprenyl (a MAO-B inhibitor), on 5-HT synthesis rates, measured in discrete regions of the rat brain by an autoradiographic method, using α-[14C]methyl-l-tryptophan as a tracer. MAO inhibitors have different effects on 5-HT synthesis rates in the cell bodies and areas of the nerve terminals. Moclobemide (10mg/kg, i.p. 30min before the tracer injection) and deprenyl (3mg/kg, i.p. 2h before the tracer injection) decreased the 5-HT synthesis rates in the dorsal (−18% and −22%) and median (−22% and −33%) raphe, respectively. Moclobemide also significantly decreased 5-HT synthesis in the entire nerve terminal areas investigated. The reductions were between 23% (cingulate cortex) and 50% (locus coeruleus). Deprenyl did not significantly affect 5-HT synthesis in the nerve terminals. The present results suggest that MAO-A, and to a lesser extent, MAO-B, are involved in the regulation of 5-HT synthesis in the rat brain. The mechanism(s) of MAO inhibitors’ action on 5-HT synthesis in the raphe nuclei are probably related to an increase in the extraneuronal 5-HT concentration and also to the interaction between the serotonergic and catecholaminergic neurons. The reduction of 5-HT synthesis in the raphe nuclei likely occurs by an action of extracellular 5-HT via the dendritic autoreceptors with a possible contribution from the action of extracellular DA and NE. In the terminal regions, the most likely mechanism is via the presynaptic autoreceptors through which elevated extraneuronal 5-HT acts on synthesis control. However, there is also a possibility that the elevation in intraneuronal 5-HT directly inhibits its synthesis, especially following deprenyl treatment. A great influence of moclobemide on 5-HT synthesis could be related to its antidepressant action. [Copyright &y& Elsevier]

Reports a case of neuroleptic malignant syndrome (NMS) following withdrawal of amantadine in a 14-year-old male with influenza A encephalopathy. Information on NMS; Association of NMS with the sudden withdrawal of amantadine in a patient with influenza A encephalopathy; Importance of the dopamine receptor blockade for the appearance of NMS.

Hepatoblastoma is a common hepatic tumor in children. Although evidence regarding cytogenetic and molecular genetic alterations in hepatoblastomas has been reported, the molecular events affecting the biologic characteristics of this tumor, including alterations of the gene expression profile, are largely unknown. To identify genes differentially expressed between nondiseased liver (NDL) and hepatoblastoma tumor (HBT), we analyzed the gene expression profile in 14 NDL and 16 HBT samples using a high-density oligonucleotide DNA array. Using Mann-Whitney U test followed by the k-nearest neighbor algorithm, we identified 26 genes (predictor genes) that were able to assign unknown samples derived from NDL and HBT to either the NDL group or HBT group with 100% accuracy. Using a cross-validation approach, we confirmed that the k-nearest neighbor algorithm assigned the particular samples derived from NDL and HBT to either the NDL or HBT group with 93.3% (28/30 samples) accuracy. In the 26 predictor genes, we found alteration of the expression of genes regulating cell division (NAP1L1, STMN1, CCNG2, and CDC7L1) and tumor cell growth (IGF2 and IGFBP4) in HBT. Four predictor genes (ETV3, TPR, CD34, and NR1I3) were also found to be mapped to the chromosomal region 1q21∼q32, which has been reported to be frequently involved in the development of hepatoblastoma. The findings obtained in this study suggest that alteration of the expression of some genes regulating cell division and tumor cell growth may be characteristics of the gene expression profile in HBT, and that alteration of the expression of the four predictor genes mapped to chromosomal region 1q21∼q32 may also contribute to the differences in gene expression profile between NDL and HBT. [Copyright &y& Elsevier]

We describe a patient with natural killer (NK)/T cell lymphoma who relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT) and was successfully treated with Escherichia coli (E. coli) and Erwinia L-asparaginase. A 38-year-old male patient with ulcerated tumor at the left thigh was diagnosed as having nasal type NK/T cell lymphoma on the basis of histopathological and flowcytometric findings of tumor, revealing diffuse infiltration of atypical lymphoid cells into blood vessels and expression of CD7 and CD56 antigens, but not CD3. He had tumor infiltration in the bone marrow and at the fight lower lung field. After five cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy, the patient achieved complete remission and received high-dose chemotherapy with auto-PBSCT, although the tumor recurred in the right leg 10 months later. Despite salvage chemotherapy, followed by local irradiation and surgical amputation, a tumor recurred at the left upper gingiva 10 days after. Using E. coli L-asparaginase (6000 U/m²/day), the tumor regressed, fever was alleviated and the serum lactate dehydrogenase decreased to normal range after several days. The asparagine synthetase expression in tumor cells was immunohistochemically negative on paraffinembedded tissues. Because of the anaphylactoid reaction developing after E. coli L-asparaginase, alternative Erwinia L-asparaginase (6000 U/m²/day) was administered, resulting in regression of tumor and fever lysis. L-asparaginase is a promising agent for the treatment of NK/T cell lymphoma. [ABSTRACT FROM AUTHOR]

The effects of the tryptophan hydroxylase (TPH) inhibitor p-chlorophenylalanine (PCPA; 200 mg/kg; 3 days), and of the protein synthesis inhibitor cycloheximide (CXM, 2 mg/kg), on regional serotonin (5-HT) synthesis were studied using the α-[14C]methyl-l-tryptophan (α-[14C]MTrp) autoradiographic method. The objectives of these investigations were to evaluate the changes, if any, on 5-HT synthesis, as measured with α-MTrp method, following the inhibition of TPH by PCPA, or the inhibition of proteins synthesis by CXM. The rats were used in the tracer experiment approximately 24 h after the last dose of PCPA was administered, and in the CXM experiments, they were used 30 min following a single injection of CXM. In both experiments, the control rats were injected with the same volume of saline (0.5 ml/kg; s.c.) and at the same times as the drug injections. The results demonstrate that trapping of α-MTrp, which is taken to be related to brain 5-HT synthesis, is drastically reduced (40–80%) following PCPA treatment. The inhibition of protein synthesis with CXM did not have a significant effect on the global brain trapping of α-MTrp and 5-HT synthesis. These findings suggest that the brain trapping of α-[14C]MTrp relates to brain 5-HT synthesis, but not to brain protein synthesis. [Copyright &y& Elsevier]

Investigates the residual disease in children with acute lymphoblastic leukemia (ALL) in Japan. Clonal rearrangement of immunoglobulin genes; Effects of chemotherapy on the disease; Prognosis of childhood ALL.

Evaluates the clinical implications of CD45 expression in acute childhood lymphoblastic leukemia (ALL). Measurement of CD45 expression of blast cells; CD45 expression in patients with hyperdiploidy versus normal karyotype; Correlation of degree of antigen expression with treatment outcome of B-precursor ALL children.

We analysed T-cell receptor α-chain variable region (TCRAV) and T-cell receptor β-chain variable region (TCRBV) repertoires in peripheral blood mononuclear cells (PBMCs) from 34 recipients of allogeneic bone marrow transplantation (allo-BMT), seven of allogeneic peripheral blood stem cell transplantation and 19 of autologous peripheral blood stem cell transplantation using the quantitative microplate hybridization assay. TCR usage skewed at an early period (6–7 weeks) after BMT. The change was more apparent in allogeneic recipients than in autologous recipients. In particular, a predominant increase was detected in the frequency of VA1-4 (26%, 11 of 41 recipients), VA3-1 (32%) and VB24-1 (28%). Interestingly, acidic amino acid residues frequently followed the arginine residue in complementarity-determining region 3 of BV24S1. We further examined the extent of skew using samples obtained at serial time points after transplantation. The normalization of skewed repertoires occurred over a long period of time (> 8 years). There was a significant difference in the rate of normalization of skewed TCR repertoires between adult and child recipients (P < 0·05). The results suggest that these T cells may have expanded in response to allogeneic antigens, such as miHA (minor histocompatibility antigen), and that altered repertoires are eventually normalized by T-cell regeneration via a thymic-dependent pathway in children. [ABSTRACT FROM AUTHOR]