Search PubMed⌕ Search

Biomedical subjects

Jun Takahashi

Publications and source records attributed to Jun Takahashi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Surgical treatment with instrumentation for severely destructive spondyloarthropathy of cervical spine.

Nine patients with severely destructive spondyloarthropathy and marked neurologic deficits associated with dialysis-related amyloidosis underwent posterior decompression and fusion by means of instrumentation at our institute. All patients showed segmental kyphosis, six patients vertebral ankylosis, and eight patients spondylolisthesis. Spondylolisthesis at two levels was noted in three patients. Of the 11 levels of spondylolisthesis in all, 9 were proximally adjacent and 2 were distally adjacent to vertebral ankylosis. All patients underwent posterior decompression and multisegment fusion with autogenous iliac bone. From three to five spinal segments were fixed. Seven patients underwent posterior fusion by means of a pedicle or lateral mass screw between levels C3 and C7, one patient between C3 and C6, and one between C3 and T1. The clinical rate of improvement at the final follow-up was 74.3%. Though complete stability could not be achieved in three patients, the results were rated as good. No postoperative neurologic deterioration has been observed in this series, nor did any patients die immediately after surgery or during the postoperative follow-up period. As anterior long-span surgery might be too invasive for hemodialysis patients, we think that posterior decompression and fusion may well be a reasonable and effective strategy for severe hemodialysis-associated cervical spondyloarthropathy with neurologic deficits. To achieve complete stability, 360 degrees fusion with both anterior and posterior fixation with instrumentation may be required for these patients.

Aged↗
PubMed2005

Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.

Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy in PD. We previously described a strong neuralizing activity present on the surface of stromal cells, named stromal cell-derived inducing activity (SDIA). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acts synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP-treated) monkeys, a primate model for PD. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Embryonic stem cells as a cell source for treating Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterised by a loss of midbrain dopaminergic (DA) neurons. Transplantation of DA neurons represents a promising treatment for PD, and embryonic stem (ES) cells are a good candidate source for DA neurons. However, although recent reports have demonstrated that DA neurons can be efficiently induced from ES cells and function therapeutically in an animal model of PD, many problems remain to be solved in order for ES cells to be used for clinical applications. This review will describe the current status of this field and the obstacles yet to be overcome, and will outline future research approaches from the clinical perspective.

Cell Culture Techniques↗
PubMed2005

Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain.

OBJECT: Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation. METHODS: Multipotential NPCs were generated from ESCs by using the stromal cell-derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 +/-2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 +/- 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)-positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, beta-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 +/-11.5% were positive for glutamate decarboxylase, 13.3 +/- 5.8% for glutamate, 2.1 +/- 2.5% for tyrosine hydroxylase, 1.8 +/- 2% for serotonin, and 0.4 +/- 0.2% for choline acetyltransferase. CONCLUSIONS: The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.

Animals↗
PubMed2004

Neural precursor cells derived from human embryonic brain retain regional specificity.

Recent studies have revealed that neural precursor cells can be expanded not only from the subventricular zone and hippocampus but also from other regions of the human embryonic brain. To determine the regional differences of these precursor cells, we divided the brain of a 9-week-old human embryo into four parts, i.e., telencephalon, diencephalon, mesencephalon, and rhombencephalon. All cultures of the tissues yielded neurospheres, and these spheres gave rise to neurons, astrocytes, and oligodendrocytes. An analysis of clonal populations revealed that these precursor cells were multipotent, and two region-specific differences in neural precursor cells were revealed: 1) The precursor cells from the rostral part of the brain tended to proliferate faster than those from the caudal part, and 2) the precursor cells from the diencephalon and mesencephalon gave rise to more tyrosine hydoxylase (TH)-positive neurons than those from the telencephalon and rhombencephalon. When 50-day-cultured spheres were caused to differentiate, the percentage of TH-positive cells per total cell population was 1.2% for diencephalic and mesencephalic precursors, whereas it was 0.4% for telencephalic and rhombencephalic ones. Furthermore, the TH-positive cells from diencephalic and mesencephalic precursors were large, multipolar, and gamma-aminobutyric acid (GABA)-negative, which suggested that these cells were midbrain dopaminergic neurons. In contrast, TH-positive cells from telencephalic and rhombencephalic precursors were small, bipolar, and GABA-positive. These results suggest that human neural precursor cells might have the potential to differentiate into a variety of cells but retain regional specificity.

Animals↗
PubMed2004

Multisensory convergence at human temporo-parietal junction - epicortical recording of evoked responses.

OBJECTIVE: Previous lesion studies in patients and functional imaging studies in normal subjects have led to the notion that the temporo-parietal junction (TPJ) has an integrative function for multisensory inputs. However, its electrophysiological properties such as response latencies and distributions of responses to various stimulus modalities in humans have not been fully investigated. The aim of the study is to clarify this issue. METHODS: We recorded evoked potentials to different kinds of sensory stimuli including somatosensory, auditory and visual modalities in 6 patients with intractable partial epilepsy, who underwent chronic implantation of subdural electrodes in TPJ for presurgical evaluation. RESULTS: In 5 out of 6 subjects, at least one electrode located in TPJ for each subject showed a maximum somatosensory evoked response commonly to electric, passive joint motion and pain stimuli. These electrodes showed the maximum responses also to tone stimuli in all of 4 subjects studied, and to visual motion stimuli in 3 out of 5 subjects studied. The polarity was consistent regardless of the stimulus modality within each individual subject, although the anatomical location, polarity and latency varied among subjects. CONCLUSIONS: A small area in TPJ for each individual subject receives sensory information of multiple modalities possibly coming from different receptive sites, although the electrophysiological properties of the responses may vary among subjects. SIGNIFICANCE: We confirmed the convergence of somatosensory, auditory and visual evoked responses at human TPJ.

Adolescent↗
PubMed2004

Electric stimulation on human cortex suppresses fast cortical activity and epileptic spikes.

PURPOSE: To investigate underlying mechanisms and adequate parameters for electric cortical stimulation to inhibit epileptic focus in humans. METHODS: A patient with intractable partial epilepsy had subdural electrodes implanted for preoperative evaluation. Cortical functional mapping was performed by using 50-Hz alternating square pulse of 0.3-ms duration, 1 to 7 mA, within 5 s. Spike frequency and electrocorticogram (ECoG) power spectra were compared before and after the stimulation when epileptic focus and distant area were stimulated. A similar comparison also was performed in low-frequency stimulation of 0.9 Hz applied for 15 min. RESULTS: Interictal spikes were reduced after electric cortical stimulation of the epileptic area at a frequency of 50 Hz as well as 0.9 Hz, with concomitant decrease in the electrographic fast activities at 50-Hz stimulation. CONCLUSIONS: These data suggest that electric cortical stimulation at both high and low frequency has a suppressive effect on epileptic activities in human cortex, possibly through distinct mechanisms.

Adult↗
PubMed2004

A combined subtemporal and transventricular/transchoroidal fissure approach to medial temporal lesions.

OBJECTIVE: To minimize therapeutic morbidity such as cognitive function disturbance and vascular injury to perforating arteries, preoperative functional mapping of the basal temporal lobe functions was performed and the medial temporal lesions were resected via a combined subtemporal and transventricular/transchoroidal fissure approach. METHODS: Twenty-one patients with medial temporal lesions including tumors, arteriovenous malformations, and medial temporal lobe epilepsy underwent operation. The neurovascular structures in the ambient cistern were first dissected free from the medial temporal lobe with a conventional subtemporal approach. Then, the temporal horn was opened through the basal surface of the temporal lobe. Finally, the ambient cistern was accessed from the temporal horn through the choroidal fissure. In five patients whose lesions were revealed to be located on the dominant side by preoperative intracarotid amytal administration test (Wada test), functional mapping of the basal temporal lobe language cortex was monitored for 1 week by use of a subdural electrocorticogram grid before the extirpation surgery. The entrance point from the temporal base to the temporal horn was determined by the result of the functional mapping. RESULTS: The lesions were resected safely and completely in all cases. Language and cognitive functions were preserved even in patients with the basal language area on the dominant side. CONCLUSION: Surgeons can confirm the important neurovascular structures from the subtemporal route and from the transtemporal horn route by a combined subtemporal and transventricular/transchoroidal fissure approach. This approach is especially effective for avoiding ischemic complications by allowing direct confirmation of the anterior choroidal and thalamoperforating arteries.

Adult↗
PubMed2004

[Vertebroplasty].

Vertebroplasty for pseudoartrosis of vertebral fracture using PMMA (polymethylmetacrylate) or CPC (calcium phosphate cement) is a new less invasive surgical method providing sufficient pain relief and correction of kyphosis.

Calcium Phosphates↗
PubMed2003

Deficit of CD38/cyclic ADP-ribose is differentially compensated in hearts by gender.

To elucidate whether myocardial CD38/cyclic ADP-ribose (cADPR) signaling plays a physiological role, we investigated the heart of CD38 knockout mice (CD38KO). In CD38KO, the myocardial cADPR content was reduced by 85% compared with wild-type mice (WT). Cardiac hypertrophy developed only in males. At 36 degrees C, none of the parameters for Ca(2+) transients and forces of the papillary muscles differed between WT and CD38KO. In contrast, at 27 degrees C, at which cADPR does not work, the peak [Ca(2+)](i) was increased and the decline in [Ca(2+)](i) was accelerated in CD38KO compared with WT. In CD38KO, the protein expression of SR Ca(2+) ATPase type2 (SERCA2) and the SERCA2-to-phospholamban ratio were increased compared with WT. The ryanodine receptor protein was increased only in female CD38KO compared with WT. These data suggest that the CD38/cADPR signaling plays an important role in intracellular Ca(2+) homeostasis in cardiac myocytes in vivo. Its deficiency was compensated differentially according to gender.

ADP-ribosyl Cyclase↗
PubMed2003

Influence of immobilization stress on the expression and phosphatase activity of protein phosphatase 2A in the rat brain.

BACKGROUND: Protein phosphatase 2A (PP2A) is a major kinase phosphatase that plays an important role in regulating the activities of protein kinase cascades. It has been revealed that stress changes neuronal gene expression by activating these cascades. We examined the expression of the catalytic subunit C and serine and threonine phosphatase activity of PP2A in the rat frontal cortex and hippocampus following various immobilization stress paradigms. METHODS: Immunoblot and immunohistochemical analyses were performed to examine the expression of PP2A. The level of phosphatase activity of PP2A was determined as the amount of free phosphate generated from a synthetic phosphopeptide. RESULTS: Immunoblot analysis revealed no significant change in the level of PP2A immunoreactivity in response to either a single or repeated stress. Immunohistochemical analysis revealed that neither a single nor repeated stress changed PP2A immunoreactivity in the hippocampus; however, the levels of serine and threonine phosphatase activity in the frontal cortex and hippocampus were significantly upregulated in response to a single or repeated stress. CONCLUSIONS: These results demonstrated that both a single and repeated immobilization stress upregulated the activity of PP2A in the rat brain, suggesting that PP2A may be involved, at least in part, in the downregulation of protein kinase activation induced by stress.

Animals↗
PubMed2003

Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells.

Recent evidence suggests that adult neural stem/progenitor cells (ANSCs) secrete autocrine/paracrine factors and that these intrinsic factors are involved in the maintenance of adult neurogenesis. We identified a novel secretory molecule, stem cell-derived neural stem/progenitor cell supporting factor (SDNSF), from adult hippocampal neural stem/progenitor cells by using the signal sequence trap method. The expression of SDNSF in adult central nervous system was localized to hippocampus including dentate gyrus, where the neurogenesis persists throughout life. In induced neurogenesis status seen in ischemically treated hippocampus, the expression of SDNSF was up-regulated. As functional aspects, SDNSF protein provided a dose-dependent survival effect for ANSC following basic fibroblast growth factor 2 (FGF-2) withdrawal. ANSCs treated by SDNSF also retain self-renewal potential and multipotency in the absence of FGF-2. However, SDNSF did not have mitogenic activity, nor was it a cofactor that promoted the mitogenic effects of FGF-2. These data suggested an important role of SDNSF as an autocrine/paracrine factor in maintaining stem cell potential and lifelong neurogenesis in adult central nervous system.

Amino Acid Sequence↗
PubMed2003

Should increasing the dose or adding an AT1 receptor blocker follow a relatively low dose of ACE inhibitor initiated in acute myocardial infarction?

OBJECTIVE: Based on currently available clinical evidence, we should use high-dose angiotensin converting enzyme inhibitor (ACE-I) for patients with acute myocardial infarction (MI), initiating it at incremental doses to avoid excessive hypotension. Recent animal studies with acute MI models failed to demonstrate the superiority of the combination therapy of ACE-I and angiotensin receptor blocker (ARB) to high-dose ACE-I treatment with comparable blood pressure reductions, which however might be attributed to the initiation of the targeted doses from the beginning. The aim of this study was to compare the effect of increasing the dose of ACE-I with that of adding ARB following a relatively low dose of ACE-I on the survival and left ventricular (LV) remodeling after MI. METHODS: Rats underwent left coronary artery ligation and were treated with either ACE-I temocapril (5 mg/kg/day) or vehicle for 2 weeks, which was initiated 3 days after the surgery. The rats treated with temocapril were further randomly assigned to receive either high-dose temocapril (10 mg/kg/day) or combination therapy (temocapril 5 mg/kg/day+olmesartan 2.5 mg/kg/day), which was continued for another 6 weeks. RESULTS: Both treatments similarly reduced the blood pressure, improved survival and ameliorated LV enlargement. In contrast, several parameters of LV function were significantly ameliorated only by the high-dose ACE-I but not by the combination therapy. CONCLUSIONS: After the initiation of a relatively low dose of ACE-I in acute MI, increasing the dose of ACE-I or adding ARB may equally improve survival and LV remodeling in the setting of an equal hypotensive effect. Further study with a longer treatment protocol is required to determine whether the several favorable effects on LV function elicited only by the high-dose ACE-I treatment provide further beneficial effects on survival and LV remodeling compared with the combination therapy.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2003

Clinical outcome and survival after palliative surgery for spinal metastases: palliative surgery in spinal metastases.

BACKGROUND: The authors sought to identify treatment-related factors that influenced survival after surgical treatment for metastatic spinal tumors and to evaluate the relationship between survival and postoperative ambulation time as a factor related to quality of life. METHODS: The medical records of 81 patients with metastatic spinal tumors who underwent palliative surgery at the study institution were assessed. Univariate analysis for factors influencing survival used the Kaplan-Meier log rank statistic and multivariate analysis used the Cox proportional hazards model. The Spearman correlation test was used to analyze the relationship between postoperative ambulation and survival time. RESULTS: The patients had a median age of 59.9 years and a median survival of 10.6 months after surgery. For patients, postoperative ambulatory median survival was 16.5 months and median ambulation time was 13.8 months. By univariate analysis, anatomic site of the primary tumor, postoperative ambulation, and combined adjuvant therapy (chemotherapy plus radiotherapy) were associated with prolonged survival (P < 0.05). Multivariate analysis identified primary site and postoperative ambulatory function as independent predictors of prolonged survival (P < 0.0001). Significant correlations were found between ambulation time and survival time of patients who were able to walk after surgery (P < 0.0001), even in patients with liver (P < 0.05) or lung carcinoma (P < 0.05). CONCLUSIONS: The anatomic site of primary carcinoma and postoperative ambulation were associated with longer survival after palliative surgery for metastatic spinal tumor. When ambulation is attained after surgery, it can be preserved until late in remaining life even when the primary tumor is unfavorable. Palliative surgery for spinal metastasis can improve the quality and quantity of life.

Early Ambulation↗
PubMed2003

Intercalary and supernumerary regeneration in the limbs of the frog, Xenopus laevis.

Anuran amphibians, such as Xenopus laevis, can regenerate their limbs only when they are young tadpoles, whereas urodele amphibians have a regenerative ability throughout their lives. It is still unclear whether anuran and urodele use the same mechanism during regeneration. In the present study, we analyzed intercalary and supernumerary regeneration in Xenopus. In contrast to urodele blastema that induces intercalary regeneration along the proximodistal (PD) axis, intercalation did not occur in the Xenopus limb bud when the presumptive zeugopodium (fibula and tibia) was removed. However, when the limb bud tip (presumptive autopodium) was transplanted to the presumptive stylopodium (femur) with a 180-degree rotation at stage 52, the complete zeugopodium was regenerated. These results were similar to the results of urodele mature limbs, suggesting that Xenopus limb buds are equivalent to the urodele mature limbs but not to the urodele blastemas. We hypothesized that the ability for intercalation depends on the expression pattern of fibroblast growth factor (fgf)-8, because the expression of fgf-8 in the urodele spreads over the whole blastema and is close enough to activate the growth of the stump. To test this hypothesis, an FGF-8-soaked bead was implanted at the boundary between the stump and tip of a Xenopus limb bud. Intercalary regeneration was induced at stages 52 and 53. These results suggest that the Xenopus limb bud possesses the potential for intercalation, but endogenous FGF-8 in the apical ectodermal ridge (AER) does not induce intercalation to the stump because of the long distance between the AER and stump.

Animals↗
PubMed2003

Repair of a proximal femoral bone defect in dogs using a porous surfaced prosthesis in combination with recombinant BMP-2 and a synthetic polymer carrier.

Total hip arthroplasty (THA) has become an almost standard procedure for the treatment of various hip lesions. However, one of the limitations has been the mechanical loosening of the prosthesis, a condition termed peri-prosthetic osteolysis. Consequently, at revision surgery, various grades of bone defect are often noted. Alternative approaches aimed at overcoming this problem have included a special design of the revision prosthesis and allo- or autogeneic bone grafting in combination with or without biomaterials. In a further attempt to address the loosening of the prosthesis, we have combined human bone morphogenetic protein-2, produced by DNA recombination (rhBMP-2) with a new synthetic biodegradable polymer (poly-D,L-lactic-acid-para-dioxanone-polyethyleneglycol block co-polymer; PLA-DX-PEG). We present data on the efficacy of the rhBMP-2 laden prosthesis to reconstruct a bone defect in a canine model. In this model, medial half of the proximal femur was surgically resected to create a bone defect that was repaired with the rhBMP-2/PLA-DX-PEG composite. Twelve weeks after implantation, the original bone defects in the rhBMP-2 treatment groups had been repaired. Thus, this type of 'hybrid' prosthesis may provide a new modality to repair bone defects or restore lost bone mass encountered in revision arthroplasty.

Absorbable Implants↗
PubMed2003

Anterior thoracic spinal fusion in dogs by injection of recombinant human bone morphogenetic protein-2 and a synthetic polymer.

The purpose of this study was to achieve spinal fusion in the absence of bone graft material using a new, injectable, and semi-liquid synthetic polymer (polylactic acid polyethylene glycol [PLA-PEG] block copolymer) containing recombinant human bone morphogenetic protein-2 (rhBMP-2). Twenty-seven skeletally mature beagles underwent anterior thoracic spinal fusion at T9-T10. Group I (n = 9) was injected with 1 mL of PLA-PEG block copolymer carrier alone into space under the vertebral pleura and the anterior longitudinal ligament. Group II (n = 9) was injected with 1 mL of PLA-PEG carrier containing 500 microgram of rhBMP-2. Group III (n = 9) was injected with 1 mL of PLA-PEG carrier containing 1000 microgram of rhBMP-2. In the Group I animals, no evidence of new bone formation was noted at the implanted sites both radiographically and histologically. In contrast, all of the nine animals in Group III showed new bone formation in 12 weeks, and four of the nine animals in Group II showed bony mass at the injected sites. However, vertebral bony fusion was incomplete despite the significant amount of new bone formation in both groups that showed new bone formation. In addition to resulting in improvements in the surgical procedure, injection of rhBMP-2 and a synthetic polymer is useful for bone formation for spinal fusion.

Animals↗