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Biomedical subjects

Jun Takahashi

Publications and source records attributed to Jun Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

Computer-assisted screw insertion for cervical disorders in rheumatoid arthritis.

To reconstruct highly destructed unstable rheumatoid arthritis (RA) cervical lesions, the authors have been using C1/2 transarticular and cervical pedicle screw fixations. Pedicle screw fixation and C1/2 transarticular screw fixation are biomechanically superior to other fixation techniques for RA patients. However, due to severe spinal deformity and small anatomical size of the vertebra, including the lateral mass and pedicle, in the most RA cervical lesions, these screw fixation procedures are technically demanding and pose the potential risk of neurovascular injuries. The purpose of this study was to evaluate the accuracy and safety of cervical pedicle screw insertion to the deformed, fragile, and small RA spine lesions using computer-assisted image-guidance systems. A frameless, stereotactic image-guidance system that is CT-based, and optoelectronic was used for correct screw placement. A total of 21 patients (16 females, 5 males) with cervical disorders due to RA were surgically treated using the image-guidance system. Postoperative computerized tomography and plane X-ray was used to determine the accuracy of the screw placement. Neural and vascular complications associated with screw insertion and postoperative neural recovery were evaluated. Postoperative radiological evaluations revealed that only 1 (2.1%; C4) of 48 screws inserted into the cervical pedicle had perforated the vertebral artery canal more than 25% (critical breach). However, no neurovascular complications were observed. According to Ranawat's classification, 9 patients remained the same, and 12 patients showed improvement. Instrumentation failure, loss of reduction, or nonunion was not observed at the final follow-up (average 49.5 months; range 24-96 months). In this study, the authors demonstrated that image-guidance systems could be applied safely to the cervical lesions caused by RA. Image-guidance systems are useful tools in preoperative planning and in transarticular or transpedicular screw placement in the cervical spine of RA patients.

Aged↗
PubMed2006

Posterior correction and fusion for severe cervical kyphosis in a patient with myotonic dystrophy: a case report.

STUDY DESIGN: A case report. OBJECTIVE: To report the first myotonic dystrophy case in which cervical kyphosis had been surgically corrected. SUMMARY OF BACKGROUND DATA: Myotonic dystrophy is an autosomal dominant disease that shows myotonia, progressive muscle atrophy, and other various symptoms. Instability of the neck is expected to cause disorders of the cervical spine; however, there are no detailed reports on deformity of cervical spine associated with this disease. METHODS: A 43-year-old man with cervical kyphosis due to myotonic dystrophy had undergone an occiput-T2 fusion with autogenous iliac bone using spinal instrumentation. RESULTS: The activity of daily life of the patient had improved markedly, and the good results continued to be preserved for 5 years. There were not any major perioperative complications. CONCLUSIONS: Surgical correction of cervical spine is not necessarily a contraindication for myotonic dystrophy.

Adult↗
PubMed2006

Grb2 and Gads exhibit different interactions with CD28 and play distinct roles in CD28-mediated costimulation.

Although both CD28 and ICOS bind PI3K and provide stimulatory signal for T cell activation, unlike CD28, ICOS does not costimulate IL-2 secretion. CD28 binds both PI3K and Grb2, whereas ICOS binds only PI3K. We have generated an ICOS mutant, which can bind Grb2 by replacement of its PI3K binding motif YMFM with the CD28 YMNM motif, and shown that it induces significant activation of the IL-2 promoter. However, this mutant ICOS was insufficient to activate the NF-kappaB pathway. In this study, we show that Gads, but not Grb2, is essential for CD28-mediated NF-kappaB activation, and its binding to CD28 requires the whole CD28 cytoplasmic domain in addition to the YMNM motif. Mutagenesis experiments have indicated that mutations in the N-terminal and/or C-terminal PXXP motif(s) of CD28 significantly reduce their association with Gads, whereas their associations with Grb2 are maintained. They induced strong activity of the NFAT/AP-1 reporter comparable with the CD28 wild type, but weak activity of the NF-kappaB reporter. Grb2- and Gads-dominant-negative mutants had a strong effect on NFAT/AP-1 reporter, but only Gads-dominant-negative significantly inhibited NF-kappaB reporter. Our data suggest that, in addition to the PI3K binding motif, the PXXP motif in the CD28 cytoplasmic domain may also define a functional difference between the CD28- and ICOS-mediated costimulatory signals by binding to Gads.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Reduced inotropic effect of nifekalant in failing hearts in rats.

Class III antiarrhythmic agents have been widely used to suppress ventricular tachyarrhythmias in patients with heart failure because they have been shown to have positive inotropic effects as well. However, it remains to be examined whether those agents also exert positive inotropic effects in failing hearts. We addressed this important issue in a rat model of heart failure. We used Nifekalant as a representative class III antiarrhythmic agent. Four weeks after a s.c. injection of 60 mg/kg monocrotaline (MCT) or vehicle (Ctr) into rats, we obtained trabeculae from right ventricles and measured the developed force and intracellular Ca(2+) ([Ca(2+)](i)) by the fura-2 microinjection method. The sarcoplasmic reticulum (SR) Ca(2+) content was assessed by the rapid-cooling contracture (RCC) technique. MCT rats exhibited right ventricular hypertrophy induced by pressure overload. The protein expression of SR Ca(2+) ATPase type 2 (SERCA2) and the SERCA2/phospholamban ratio in MCT rats was lower with a slower decline of Ca(2+) transients and a reduced amplitude of RCCs. Nifekalant concentration-dependently increased the force, peak [Ca(2+)](i), and the amplitude of RCCs in Ctr rats but not in MCT rats with identical prolongation of the action potential. Under the SR inhibited with cyclopiazonic acid and ryanodine, Nifekalant increased the force in Ctr rats but not in MCT rats. These results indicate that the positive inotropic effects of Nifekalant is reduced in failing hearts, probably due to the depressed SR Ca(2+) uptake and reduced reserve of the trans-sarcolemmal Ca(2+) transport, warranting a caution in the antiarrhythmic therapy with a class III antiarrhythmic agent in heart failure.

Action Potentials↗
PubMed2006

Generation of graftable dopaminergic neuron progenitors from mouse ES cells by a combination of coculture and neurosphere methods.

Parkinson's disease is characterized by a loss of midbrain dopamine (DA) neurons and is generally viewed as a potential target for stem cell therapy. Although several studies have reported the generation of postmitotic DA neurons from embryonic stem (ES) cells, it is unknown whether the proliferative progenitors of DA neurons can be isolated in vitro. To investigate this possibility, we have developed a combined approach in which ES cells are cocultured with PA6 stromal cells to expose them to stromal cell-derived inducing activity (SDIA) and are then cultured as neurospheres. Mouse ES cell colonies were detached from PA6 feeder cells after 8 days of SDIA treatment and then expanded as spheres for another 4 days in serum-free medium supplemented with fibroblast growth factor-2. The spheres exhibited neural stem cell characteristics and contained few DA neurons at this stage of culture. After being induced to differentiate on polyornithine/laminin-coated dishes for 7 days, these spheres generated DA neurons in vitro at a relatively low frequency. Intriguingly, addition of PA6 cell conditioned medium to the sphere culture medium significantly increased the percentage of DA neurons to 25-30% of the total number of neurons. Transplantation of conditioned medium-treated day 4 spheres, which contained DA neuron progenitors, into the mouse striatum resulted in the generation of a significant number of graft-derived DA neurons. These findings suggest that progenitors of DA neurons are generated and can proliferate in ES cell-derived neurospheres induced by serial SDIA and PA6 conditioned medium treatment.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2006

Usefulness of white blood cell differential for early diagnosis of surgical wound infection following spinal instrumentation surgery.

STUDY DESIGN: The white blood cell (WBC) count and WBC differential were measured prospectively in patients after spinal instrumentation surgery with or without surgical wound infection. OBJECTIVES.: To investigate the usefulness of WBC differential for early diagnosis of surgical wound infection after spinal instrumentation surgery. SUMMARY OF BACKGROUND DATA: Renewed elevation of C-reactive protein (CRP) or WBC, gallium scan, and CRP/transthyretin mass concentration ratio were reported for early diagnosis of surgical wound infection. METHODS: A total of 39 patients were enrolled in this study: 13 patients who developed wound infection within 2 weeks after spinal instrumentation surgery (infection group) and 26 patients who were comparable with those patients included in the infection group with regard to age, sex, and surgical techniques used (control group). The WBC count and WBC differential were determined before and after surgery. RESULTS: In both groups, WBC and percentage and number of neutrophils showed nearly same change until postoperative 4 days (day 4). However, in the infection group, these parameters had increased after day 4. In both groups, the percentage and number of lymphocytes decreased to 10% or less and 1,000/microL or less on day 1, respectively. These lymphocyte parameters began to gradually normalize on day 4 and returned to the preoperative level 3 weeks after surgery in the control group. On the other hand, these parameters remained 10% or less and 1,000/muL or less until day 11 in the infection group. In patients with infection, the percentage and number of lymphocytes significantly decreased as early as on day 4. CONCLUSION: Lymphopenia represents immunodepression status, thus indicating the increased susceptibility to infection, which may lead to the development of postoperative infection. If lymphopenia is diagnosed as early as possible, surgical wound infection can be treated promptly without removing the instruments.

Adolescent↗
PubMed2006

Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: effect of in vitro differentiation on graft survival and teratoma formation.

Human embryonic stem cells (hESCs) have been proposed as a source of dopamine (DA) neurons for transplantation in Parkinson's disease (PD). We have investigated the effect of in vitro predifferentiation on in vivo survival and differentiation of hESCs implanted into the 6-OHDA (6-hydroxydopamine)-lesion rat model of PD. The hESCs were cocultured with PA6 cells for 16, 20, or 23 days, leading to the in vitro differentiation into DA neurons. Grafted hESC-derived cells survived well and expressed neuronal markers. However, very few exhibited a DA neuron phenotype. Reversal of lesion-induced motor deficits was not observed. Rats grafted with hESCs predifferentiated in vitro for 16 days developed severe teratomas, whereas most rats grafted with hESCs predifferentiated for 20 and 23 days remained healthy until the end of the experiment. This indicates that prolonged in vitro differentiation of hESCs is essential for preventing formation of teratomas.

Animals↗
PubMed2006

Clinical outcome of patients with SREDA (subclinical rhythmic EEG discharge of adults).

OBJECTIVE: To clarify the clinical significance of subclinical rhythmic EEG discharge of adults' (SREDA) by analyzing characteristics of SREDA and the outcome of patients based on retrospective analysis of EEG data base. METHODS: EEGs were recorded soon after the onset of patient's initial symptoms and repeatedly recorded at various intervals of 2-3 months in all 4 patients. Neurological findings, MRI and SPECT were also investigated. SUBJECTS: Out of 340 consecutive inpatient population who had EEGs, 4 patients (1.2%) showed SREDA. They had a diagnosis of syncope, transient global amnesia, generalized tonic-clonic seizure and right temporal lobe epilepsy for each. RESULTS: There was no consistent abnormality in the brain MRI, CT or SPECT among the 4 patients. The acute and transient symptoms disappeared and did not recur within the follow-up period of 28 months in any patient. In 2 patients SREDA disappeared in the follow-up EEG taken 7-14 days after the first EEG showing SREDA. In the other 2 patients, the follow-up EEGs taken 5 days after the first EEG with SREDA when clinical symptoms disappeared showed less frequent occurrence of SREDA. CONCLUSION: Being different from the previous reports suggesting the relation with cardiogenic insults or persistent ischemic abnormality, SREDA can occur in patients with various acute brain dysfunctions followed by a favorable clinical outcome.

Adolescent↗
PubMed2006

Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain.

Transplantation of stem cells has the possibility of restoring neural functions after stroke damage. Therefore, we transplanted neuronal progenitors generated from monkey embryonic stem (ES) cells into the ischemic mouse brain to test this possibility. Monkey ES cells were caused to differentiate into neuronal progenitors by the stromal cell-derived inducing activity method. Focal cerebral ischemia was induced by occluding the middle cerebral artery by the intraluminal filament technique. The donor cells were transplanted into the ischemic lateral striatum at 24 h after the start of reperfusion. The cells transplanted into the ischemic brain became located widely around the ischemic area, and, moreover, the transplanted cells differentiated into various types of neurons and glial cells. Furthermore, at 28 days after the transplantation, over 10 times more cells in the graft were labeled with Fluorogold (FG) by stereotactic focal injection of FG into the anterior thalamus and substantia nigra on the grafted side when compared with the number at 14 days. From these results we confirmed the survival and differentiation of, as well as network formation by, monkey ES-cell-derived neuronal progenitors transplanted into the ischemic mouse brain.

Animals↗
PubMed2006

Subtemporal hippocampectomy preserving the basal temporal language area for intractable mesial temporal lobe epilepsy: preliminary results.

PURPOSE: Decline in verbal memory as a surgical complication remains an unresolved problem in mesial temporal lobe epilepsy. Some areas in the temporal lobe associated with the language function, often including the basal temporal language area, have been removed or transected by conventional surgical procedures. The authors defined the basal temporal language area and removed only the epileptogenic zone with a subtemporal approach. METHODS: The basal temporal language area was evaluated by using long-term subdural electrodes in five patients with language-dominant-side mesial temporal lobe epilepsy. While preserving this area, the hippocampus and the parahippocampal gyrus were removed by using a combined subtemporal, transventricular, transchoroidal fissure approach. Verbal memory performance was assessed with the Wechsler Memory Scale-Revised (WMS-R) before and after the operation. RESULTS: The basal temporal language area, defined as a part of the inferior temporal gyrus, the fusiform gyrus, and the parahippocampal gyrus, was spared by entering the temporal horn via collateral sulcus. Verbal memory was significantly improved by 3 months and 1 year after the operation. CONCLUSIONS: In language-dominant-side mesial temporal lobe epilepsy, preserving the basal temporal language area would have potential to improve verbal memory outcomes after removal of the epileptogenic zone.

Adult↗
PubMed2006

[Efficacy and safety of monotherapy with temozolomide in patients with anaplastic astrocytoma at first relapse--a phase II clinical study].

The efficacy and safety of temozolomide were evaluated in 32 patients with anaplastic astrocytoma at first relapse. Temozolomide was administered orally once daily for the first five days of a 28-day cycle, at a dose of 150 or 200 mg/m(2)/day. The response rate determined by independent central review of MRI was 34% (95% confidence interval: 18.6%-53.2%), with 3 complete response and 8 partial response. The rate of "no change or better" was 91% (95% confidence interval: 75.0%-98.0%). Progression-free survival (PFS) at 6 months was 40.6%, and the median PFS was 4.1 months. The incidence of constipation (50%) and nausea (25%) was high,but these events were all mild or moderate in severity except in one subject with constipation,and could be managed with standard laxatives and antiemetics. The main laboratory test abnormalities (total incidence and incidence of grade 3/4 change) were lymphocytopenia (50%, 25%), neutropenia (47%, 6%), leukopenia (38%, 3%), thrombocytopenia (31%, 9%), and increased GPT (25%, 3%). Temozolomide was shown to have good efficacy and tolerability in patients with anaplastic astrocytoma at first relapse.

Adult↗
PubMed2005

Ehlers-Danlos syndrome type VIB with characteristic facies, decreased curvatures of the spinal column, and joint contractures in two unrelated girls.

Two unrelated girls, aged 11 and 14 years, with clinical manifestations of Ehlers-Danlos syndrome (EDS) type VIB, characteristic facies, skeletal abnormalities, and other features are described. They had Marfanoid habitus with pectus excavatum; fragile, hyperextensible, and readily bruisable skin with widened, atrophic scars; recurrent hematomas; generalized joint laxity; hypotonia; scoliosis; and mild delay of gross motor development. Lysyl hydroxylase deficiency was ruled out in Patient 1. Parental consanguinity was present in Patient 2. They both had, in early childhood, down-slanting palpebral fissures, drooping lower eyelids, short nose, small mouth, and long philtrum. Facial features that persisted included thick eyebrows, hypertelorism, strabismus, blue sclerae, low-set, and slanted ears, hypoplastic columella, high-arched palate, and thin upper lip. They had tubular stenosis of the phalanges, metacarpals, and metatarsals; decreased physiological curvatures of the spinal column with tall vertebrae; and joint contractures including talipes equinovarus and progressive talipes valgus. Their hearing of high-pitched sounds was impaired. They had constipation and recurrent cystitis with an enlarged bladder. In view of these findings, we propose that these two girls represent a clinically recognizable subgroup of EDS type VIB.

Adolescent↗
PubMed2005

Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation.

The differentiation of dopaminergic (DA) neurons from mouse embryonic stem cells (ESCs) can be efficiently induced, making these neurons a potential source for transplantation as a treatment for Parkinson's disease, a condition characterized by the gradual loss of midbrain DA neurons. One of the major persistent obstacles to the successful implementation of therapeutic ESC transplantation is the propensity of ESC-derived grafts to form tumors in vivo. To address this problem, we used fluorescence-activated cell sorting to purify mouse ESC-derived neural precursors expressing the neural precursor marker Sox1. ESC-derived, Sox1+ cells began to express neuronal cell markers and differentiated into DA neurons upon transplantation into mouse brains but did not generate tumors in this site. In contrast, Sox1- cells that expressed ESC markers frequently formed tumors in vivo. These results indicate that Sox1-based cell sorting of neural precursors prevents graft-derived tumor formation after transplantation, providing a promising strategy for cell transplantation therapy of neurodegenerative disorders.

Animals↗
PubMed2005

Differential regulation of diacylglycerol kinase isozymes in cardiac hypertrophy.

To examine the involvement of diacylglycerol kinase (DGK) and phosphatidic acid phosphatase (PAP) in pressure overloaded cardiac hypertrophy, rats were subjected to either ascending aortic banding for 3, 7, and 28 days or sham operation. In comparison with sham-operated rats, the left ventricular (LV) weight of the aortic-banded rats increased progressively. At 28 days after surgery, the expression of DGKepsilon mRNA but not DGKzeta or PAP2b mRNA in the LV myocardium significantly decreased in the aortic-banded rats compared with the sham-operated rats. DGKzeta protein in the LV myocardium translocated from the particulate to the cytosolic compartment in the aortic-banded rats. Furthermore, the myocardial content of 1,2-diacylglycerol and PKCdelta protein expression in the particulate fraction of the LV myocardium significantly increased in aortic-banded rats compared with sham-operated rats. These results suggest that DGKepsilon and DGKzeta play distinct roles in the development of pressure overloaded cardiac hypertrophy and that the two isozymes are differentially regulated.

Animals↗
PubMed2005

Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells.

To investigate the effect of estrogen on neuronal differentiation, especially on dopaminergic (DA) neurons, human neural stem cells (NSCs) were differentiated in the presence of 17beta-estradiol. NSCs gave rise to tyrosine hydroxylase (TH)-positive neurons in vitro, the proportion of which was increased by 17beta-estradiol. Increase in TH-positive neurons was abrogated by an estrogen receptor (ER) antagonist, ICI182780, suggesting ERs play a role in differentiation of DA neurons. The observation that ERs were expressed in both proliferating NSCs and postmitotic DA neurons suggested that increase in TH-positive neurons was due to induction and support of DA neurons. 17beta-Estradiol also increased the number of DA neurons derived from human NSCs in vivo when the cells were grafted into mouse brains. These results support a possible role for estrogen in the transplantation of NSCs for Parkinson's disease.

Animals↗
PubMed2005

Magnetic resonance and computed tomography-based scoring system for the differential diagnosis of vertebral fractures caused by osteoporosis and malignant tumors.

BACKGROUND: Previous reports have described magnetic resonance imaging (MRI) findings alleged to be specific for vertebral fractures caused by malignant lesions. Using such findings for differential diagnosis is often difficult, especially during the early phase of the fracture. With the relative inaccuracy of any single imaging finding, a validated scoring system based on a combination of imaging findings might lead to enhanced diagnostic accuracy. The purpose of this study was to establish a diagnostic scoring system for discriminating osteoporotic vertebral fractures from those caused by malignant tumors on the basis of MRI and computed tomography (CT) findings. METHODS: Ten MRI and CT scan findings of 57 osteoporotic vertebral fractures and 43 neoplastic fractures were retrospectively evaluated for their ability to discriminate between malignant and benign vertebral fractures. RESULTS: The following four MRI and two CT findings were selected as the basis for the scoring system: pedicle or other posterior element involvement; extension into the paravertebral region; preservation of normal bone marrow signal; a continuous black line representing the posterior vertebral body margin on T2-weighted MRI images; osteolytic destruction; and distinct fracture lines on CT. CONCLUSION: By combining the findings common to MRI and CT scans of vertebral fractures, a simple scoring system was devised. This scoring system was found to enhance the accuracy of imaging diagnosis of fractures caused by benign or malignant spinal lesions.

Adult↗