In order to apply human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) to regenerative medicine, the cells should be produced under restricted conditions conforming to GMP guidelines. Since the conventional culture system has some issues that need to be addressed to achieve this goal, we developed a novel culture system. We found that recombinant laminin-511 E8 fragments are useful matrices for maintaining hESCs and hiPSCs when used in combination with a completely xeno-free (Xf) medium, StemFit™. Using this system, hESCs and hiPSCs can be easily and stably passaged by dissociating the cells into single cells for long periods, without any karyotype abnormalities. Human iPSCs could be generated under feeder-free (Ff) and Xf culture systems from human primary fibroblasts and blood cells, and they possessed differentiation abilities. These results indicate that hiPSCs can be generated and maintained under this novel Ff and Xf culture system.
Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.
Induced pluripotent stem cells (iPSCs) provide the potential for autologous transplantation using cells derived from a patient’s own cells. However, the immunogenicity of iPSCs or their derivatives has been a matter of controversy, and up to now there has been no direct comparison of autologous and allogeneic transplantation in the brains of humans or nonhuman primates. Here, using nonhuman primates, we found that the autologous transplantation of iPSC-derived neurons elicited only a minimal immune response in the brain. In contrast, the allografts caused an acquired immune response with the activation of microglia (IBA-1+/MHC class II+) and the infiltration of leukocytes (CD45+/CD3+). Consequently, a higher number of dopaminergic neurons survived in the autografts. Our results suggest that the autologous transplantation of iPSC-derived neural cells is advantageous for minimizing the immune response in the brain compared with allogeneic grafts.
•iPSC-derived autografts cause only a minimal immune response in the primate brain•Autografts have advantages over allografts even at an immune-privileged site•Dopamine neurons survive even in allografts without immunosuppression
The autologous transplantation of iPSC-derived neurons elicited only a minimal immune response in the brain. In contrast, the allografts caused an acquired immune response with the activation of microglia (IBA-1+/MHC class II+) and the infiltration of leukocytes (CD45+/CD3+). Autologous transplantation is advantageous for minimizing the immune response compared with allogeneic grafts.
The majority of multiple vertebral fractures (MVFs) occur under high-energy conditions; however, some cases occurring under minor-energy conditions exist. Fractures in successive vertebrae (continuous type) and in skipped vertebrae (discontinuous type) can exist.
The objective of this study was to compare and evaluate the cause, level of injury, and relationship to osteoporosis between continuous and discontinuous MVFs.
We studied 77 subjects (173 vertebrae) who had presented with acute back pain between September 2007 and April 2010 and who received diagnoses of fresh MVFs through magnetic resonance imaging. Subjects with continuous and discontinuous fractures were evaluated based on age, sex, bone mineral density (BMD), level of affected vertebrae, and cause of injury.
Subjects with discontinuous MVFs were significantly older and comprised more female patients. Mean BMD, measured by dual-emission X-ray absorptiometry, was 0.70 and 0.58 g/cm3 for the continuous and discontinuous MVFs, respectively, demonstrating a significant difference. Of 34 patients with discontinuous MVFs, 32 (94%) exhibited vertebral fractures in the thoracolumbar junction. In subjects with continuous MVFs, the MVFs of 19 (44%) subjects were caused by high-energy trauma, whereas mild trauma and unknown cause were identified in 14 (41%) and 13 (38%) subjects with discontinuous MVFs, respectively.
Discontinuous MVFs generally caused by mild outer force, and often occurred at the thoracolumbar junction. Continuous MVFs, frequently, were caused by high-energy trauma.
Vertebral compression fractures; High energy; Low energy; Osteoporosis; Continuous type; Discontinuous type
Upper cervical or occipitocervical disorders such as rheumatoid arthritis present as atlantoaxial subluxation, vertical subluxation of the axis, and subaxial subluxation, which produce myelopathy and severe pain. In such cases, occipitocervical reconstruction surgery may be indicated, and several reports have described reduction of subluxation by fixing the halo vest before this surgery.
The purpose of this study was to evaluate the efficacy of using the halo vest before the surgery for unstable upper cervical spine and for occipitocervical instability.
Twenty-eight patients (9 men and 19 women; mean age, 61.8 years at surgery) who presented with atlantoaxial or occipitocervical fusion were studied. In all cases, the halo vest was fixed in the conscious condition, and subluxation was reduced before the surgery. The mean follow-up period was 45 months. Roentgenologic measurement and clinical evaluation were performed before the surgery and at the final follow-up.
Using the halo vest resulted in significant reductions in the atlantodental interval, the space available for the spinal cord, and the Ranawat value (p < 0.05), and these were maintained until the final follow-up. The mean Japanese Orthopedic Association score significantly improved from 9.5 before surgery to 12.2 at the final follow-up (p = 0.01). Nineteen cases (68%) improved by more than 1 grade by Ranawat’s classification after surgery and 16 cases (57%) maintained the same at the follow-up visit.
Conscious preoperative reduction using the halo vest for occipitocervical disorders is a useful and safe technique.
Occipitocervical disorders; Occipitocervical reconstruction; Halo vest
Cell replacement therapy using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is a promising strategy for the treatment of neurologic diseases such as Parkinson's disease (PD). However, a limiting factor for effective cell transplantation is the low survival rate of grafted cells, especially neurons. In this study, we modified the host environment and investigated whether the simultaneous administration of soluble factors can improve the survival and differentiation of murine iPSC-derived dopaminergic (DA) neurons in host brains. With the goal of applying this technology in clinical settings in the near future, we selected drugs that were already approved for clinical use. The drugs included two commonly used anti-convulsants, valproic acid (VPA) and zonisamide (ZNS), and estradiol (E2), also known as biologically active estrogen. Following neural induction of murine iPSCs, we collected neural progenitor cells (NPCs) by sorting PSA-NCAM+ cells, then treated the PSA-NCAM+ cells with drugs for 4 days. An immunofluorescence study revealed that 0.01 mM and 0.1 mM of VPA and 10 nM of E2 increased the percentage of tyrosine hydroxylase+ (TH: a DA neuron marker) cells in vitro. Furthermore, 0.1 mM of VPA increased the percentage of TH+ cells that simultaneously express the midbrain markers FOXA2 and NURR1. Next, in order to determine the effects of the drugs in vivo, the iPSC-derived NPCs were transplanted into the striata of intact SD rats. The animals received intraperitoneal injections of one of the drugs for 4 weeks, then were subjected to an immunofluorescence study. VPA administration (150 mg/kg/daily) increased the number of NeuN+ post-mitotic neurons and TH+ DA neurons in the grafts. Furthermore, VPA (150 mg/kg/daily) and ZNS (30 mg/kg/daily) increased the number of TH+FOXA2+ midbrain DA neurons. These results suggest that the systemic administration of VPA and ZNS may improve the efficiency of cell replacement therapy using iPSCs to treat PD.
induced pluripotent stem cells; valproic acid; zonisamide; estradiol; transplantation; dopaminergic neurons
A retrospective study.
To evaluate the surgical results of cervical pedicle screw (CPS) fixation combined with laminoplasty for treating cervical spondylotic myelopathy (CSM) with instability.
Overview of Literature
Cervical fixation and spinal cord decompression are required for CSM patients with instability. However, only a few studies have reported on CPS fixation combined with posterior decompression for unstable CSM patients.
Thirteen patients that underwent CPS fixation combined with laminoplasty for CSM with instability were evaluated in this study. We assessed the clinical and radiological results of the surgical procedures. The Japanese Orthopedic Association (JOA) scoring system was used to evaluate the clinical results. The percentages of sli p, difference in sli p angle between maximum flexion and maximum extension of unstable intervertebrae, and perforation rate of CPS were evaluated.
The mean JOA scores before surgery, immediately after surgery, and at final follow-up were 9.1, 13.3, and 12.6, respectively. The mean percentages of sli p before surgery, immediately after surgery, and at final follow-up were 9.1%, 3.2%, and 3.5%, respectively; there were significant improvements immediately after surgery and at final follow-up. The difference in sli p angle between the maximum flexion and maximum extension of the unstable intervertebrae changed from 9.0° before surgery to 1.6° at the final follow-up. The perforation rate of CPS was 10.9%.
The results suggest that CPS fixation combined with laminoplasty is an effective surgical procedure for treating CSM with instability.
Cervical spondylosis; Myelopathy; Instability; Cervical fixation
The purpose of this case report was to report a rare case of pyogenic spondylodiscitis caused by Campylobacter fetus. A 37-year-old male presented with fever and low back pain. By lumbar magnetic resonance imaging (MRI), no abnormal finding was observed at the first presentation. However, low back pain was aggravated, and fever did not improve. Thus, lumbar MRI was repeated on the 26 day after the onset of symptoms, showing abnormal signals at vertebrae and disc spaces, and pyogenic spondylitis was diagnosed. The possibility of pyogenic spondylodiscitis should be taken into account if a patient presents with low back pain and fever, and areas of low signal intensity on a T1-weighted MRI should be carefully examined. When initial MRI does not reveal abnormal findings, repeated MRI after one or two weeks or, more favorably, immediate gadolinium enhancement MRI, are important for patients who have persistent low back pain and fever.
Resonance imaging; Campylobacter fetus
Arachnoid cysts originating from the velum interpositum are very rare, and their existence as a clinicopathologic entity remains controversial. We report a case of a patient with an arachnoid cyst of the velum interpositum presenting with memory disturbance, focusing on the anatomical origin of the lesion and the physiological mechanisms causing memory disturbance.
A 65-year-old man with a large cystic lesion in the velum interpositum experienced progressive memory disturbance and enlargement of the lesion 6 months before referral to our institution. Neuropsychological evaluation on admission demonstrated severe memory disturbance. Radiological examination did not reveal hydrocephalus, but the bilateral fornices and thalami were compressed by the cyst. The patient underwent endoscopic cystoventriculostomy via the frontal horn of the right lateral ventricle through a frontal burr hole. Histopathology of the sample was consistent with that of an arachnoid cyst, and the endoscopic findings suggested that the cyst originated from the tela choroidea, which covers the velum interpositum. The symptoms resolved after surgery with significant improvement in neuropsychological test scores.
Arachnoid cysts of the velum interpositum are rare but distinct clinicopathologic entities that originate from the tela choroidea. The lesions can cause memory disturbance without hydrocephalus due to compression of the fornices and thalami, but this can be reversed by surgery.
Arachnoid cyst; neuroendoscopy; velum interpositum
A retrospective study.
To evaluate the surgical results of computer-assisted C1-C2 transarticular screw fixation for atlantoaxial instability and the usefulness of the navigation system.
Overview of Literature
We used a computed tomography (CT)-based computer navigation system in planning and screw insertion in Magerl's procedure, which provides the most rigid atlantoaxial fusion, to avoid risk of vertebral artery (VA) tear by avoiding high-riding VA during screw insertion.
Twenty patients who underwent atlantoaxial fusion under the CT-based navigation system were studied. The mean observation period was 33.5 months. The evaluated items included the existence of VA stenosis by preoperative magnetic resonance angiography, surgical time, blood loss volume, Japanese Orthopaedic Association (JOA) score and Ranawat's pain criteria before surgery and at final follow-up, postoperative screw position evaluated by CT, and bony fusion.
The mean operation time was 205 minutes, with the mean blood loss volume of 242 ml. The mean JOA score was 11.6 points before surgery and 13.7 at final follow-up. Occipital and/or cervical pain presented before operation was remitted or resolved in all patients. Evaluation of screw insertion by CT revealed correct penetration to atlantoaxial joints, with a perforation rate of 2.6%. There was no complication, including VA tear, and all patients who were followed-up during one year or more after surgery achieved bony fusion. Some subjects who appeared inappropriate for surgery from CT images were assessed as eligible for surgery based on the evaluation results obtained using the navigation system.
It was demonstrated that the CT-based navigation system is an effective support device for Magerl's procedure.
Atlantoaxial joint; Atlantoaxial instability; CT-based computer navigation system; C1-C2 transarticular screw fixation
Aqueous solutions of isovaline and its precursor molecule, 5-ethyl-5-methylhydantoin, were irradiated with ultraviolet and γ-ray photons, to evaluate their structural stability against space radiation. The degree of photolysis was measured and irradiation products were identified using chiral, reversed-phase and ion-exchange high-performance liquid chromatography. The experimental results show that the degree of photolysis of 5-ethyl-5-methylhydantoin is more significant than that of isovaline under ultraviolet light irradiation, while the results under γ-ray irradiation are the opposite. As the products of isovaline photolysis, aspartic acid, serine, glutamic acid and alanine were dominantly detected.
isovaline; space radiation; ultraviolet light; gamma ray; photolysis
We have successfully developed a surface plasmon resonance (SPR) measurement system for the on-site immunoassay of real samples. The system is composed of a portable SPR instrument (290 mm(W) × 160 mm(D) × 120 mm(H)) and a microfluidic immunoassay chip (16 mm(W) × 16 mm(D) × 4 mm(H)) that needs no external pump system. An integrated vertical capillary tube functions as a large volume (150 μL) passive pump and a waste reservoir that has sufficient capacity for several refill operations. An immunoassay was carried out that employed the direct injection of a buffer and a test sample in sequence into a microfluidic chip that included 9 antibody bands and 10 reference reagent bands immobilized in the flow channel. By subtracting a reliable averaged reference sensorgram from the antibody, we effectively reduced the influence of the non-specific binding, and then our chip successfully detected the specific binding of spiked IgG in non-homogeneous milk. IgG is a model antigen that is certain not to be present in non-homogeneous milk, and non-homogeneous milk is a model of real sample that includes many interfering foreign substances that induce non-specific binding. The direct injection of a real sample with no pretreatment enabled us to complete the entire immunoassay in several minutes. This ease of operation and short measuring time are acceptable for on-site agricultural, environmental and medical testing.
SPR; immunoassay; raw sample; on-site; passive pump; microfluidics
We have developed a measurement chip installation/removal mechanism for a surface plasmon resonance (SPR) immunoassay analysis instrument designed for frequent testing, which requires a rapid and easy technique for changing chips. The key components of the mechanism are refractive index matching gel coated on the rear of the SPR chip and a float that presses the chip down. The refractive index matching gel made it possible to optically couple the chip and the prism of the SPR instrument easily via elastic deformation with no air bubbles. The float has an autonomous attitude control function that keeps the chip parallel in relation to the SPR instrument by employing the repulsive force of permanent magnets between the float and a float guide located in the SPR instrument. This function is realized by balancing the upward elastic force of the gel and the downward force of the float, which experiences a leveling force from the float guide. This system makes it possible to start an SPR measurement immediately after chip installation and to remove the chip immediately after the measurement with a simple and easy method that does not require any fine adjustment. Our sensor chip, which we installed using this mounting system, successfully performed an immunoassay measurement on a model antigen (spiked human-IgG) in a model real sample (non-homogenized milk) that included many kinds of interfering foreign substances without any sample pre-treatment. The ease of the chip installation/removal operation and simple measurement procedure are suitable for frequent on-site agricultural, environmental and medical testing.
SPR; on-site; portable; immunoassay; magnet
Lymphocytic hypophysitis is divided into three forms according to the involved tissues, lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis, and lymphocytic panhypophysitis (LPH). The term LPH was first proposed by us in 1995, although its entity and pathogenesis still remain controversial. Here we report five cases of LPH, who visited our clinics during 1994 to 2009. All cases were female of 20 to 77 years of age, and one case was associated with pregnancy. They presented with polyuria (n = 4), headache (n = 3), general malaise, polydipsia (n = 2), blunted vision, diplopia, amenorrhea or appetite loss (n = 1). Magnetic resonance imaging showed the pituitary swelling, the thickened stalk, the loss of the T1 hyperintense neurohypophysis (n = 4), or the atrophic pituitary (n = 1). Endocrinological examinations revealed deficiencies of TSH, ADH in all cases, GH, ACTH in three cases, LH, PRL in two cases, and FSH in one case, respectively. The severity of ADH deficiency varied among the cases. Anti-pituitary antibody was not detected in the cases examined. The biopsy of the pituitary lesions was performed except for one case, all of which revealed the diffuse lymphocytic infiltration. These results suggest that LPH is characterized by the female predominance, the atypical patterns of anterior pituitary hormone deficiencies and the variable degrees of diabetes insipidus in Japanese.
lymphocytic panhypophysitis; hypopituitarism; diabetes insipidus
The advent of gene expression profiling was expected to dramatically improve cancer diagnosis. However, despite intensive efforts and several successful examples, the development of profile-based diagnostic systems remains a difficult task. In the present work, we established a method to convert molecular classifiers based on adaptor-tagged competitive PCR (ATAC-PCR) (with a data format that is similar to that of microarrays) into classifiers based on real-time PCR.
Previously, we constructed a prognosis predictor for glioma using gene expression data obtained by ATAC-PCR, a high-throughput reverse-transcription PCR technique. The analysis of gene expression data obtained by ATAC-PCR is similar to the analysis of data from two-colour microarrays. The prognosis predictor was a linear classifier based on the first principal component (PC1) score, a weighted summation of the expression values of 58 genes. In the present study, we employed the delta-delta Ct method for measurement by real-time PCR. The predictor was converted to a Ct value-based predictor using linear regression.
We selected UBL5 as the reference gene from the group of genes with expression patterns that were most similar to the median expression level from the previous profiling study. The number of diagnostic genes was reduced to 27 without affecting the performance of the prognosis predictor. PC1 scores calculated from the data obtained by real-time PCR showed a high linear correlation (r = 0.94) with those obtained by ATAC-PCR. The correlation for individual gene expression patterns (r = 0.43 to 0.91) was smaller than for PC1 scores, suggesting that errors of measurement were likely cancelled out during the weighted summation of the expression values. The classification of a test set (n = 36) by the new predictor was more accurate than histopathological diagnosis (log rank p-values, 0.023 and 0.137, respectively) for predicting prognosis.
We successfully converted a molecular classifier obtained by ATAC-PCR into a Ct value-based predictor. Our conversion procedure should also be applicable to linear classifiers obtained from microarray data. Because errors in measurement are likely to be cancelled out during the calculation, the conversion of individual gene expression is not an appropriate procedure. The predictor for gliomas is still in the preliminary stages of development and needs analytical clinical validation and clinical utility studies.
To clarify the clinical usefulness of preoperative fibre‐tracking in affected pyramidal tracts for intraoperative monitoring during the removal of brain tumours from patients with motor weakness.
We operated on 10 patients with mild to moderate motor weakness caused by brain tumours located near the pyramidal tracts under local anaesthesia. Before surgery, we performed fibre‐tracking imaging of the pyramidal tracts and then transferred this information to the neuronavigation system. During removal of the tumour, motor function was evaluated with motor evoked potentials elicited by cortical/subcortical electrical stimulation and with voluntary movement.
In eight patients, the locations of the pyramidal tracts were estimated preoperatively by fibre‐tracking; motor evoked potentials were elicited on the motor cortex and subcortex close to the predicted pyramidal tracts. In the remaining two patients, in which fibre‐tracking of the pyramidal tracts revealed their disruption surrounding the tumour, cortical/subcortical electrical stimulation did not elicit responses clinically sufficient to monitor motor function. In all cases, voluntary movement with mild to moderate motor weakness was extensively evaluated during surgery and was successfully preserved postoperatively with appropriate tumour resection.
Preoperative fibre‐tracking could predict the clinical usefulness of intraoperative electrical stimulation of the motor cortex and subcortical fibres (ie, pyramidal tracts) to preserve affected motor function during removal of brain tumours. In patients for whom fibre‐tracking failed preoperatively, awake surgery is more appropriate to evaluate and preserve moderately impaired muscle strength.
Meningiomas of the spine occur in the thoracic spine in approximately 80%, followed in frequency by the cervical and lumbar regions. The treatment of spinal meningiomas is complete surgical resection. As intraspinal meningiomas are almost always adherent to the dura, extensive dural resection or diathermic treatment of the dural attachment is usually performed to prevent tumor recurrence. The authors present the case of lumbar spinal meningioma in 82-year-old woman. Successful resection with preservation of the dura mater using the technique of Saito et al. (Spine 26:1805-1808, 2001) is described: After lumbar laminectomy a small incision was made in the surface of the spinal dura. The dura mater was separated into its inner and outer layers, and the tumor was resected with inner layer alone, preserving the outer layer. The outer layer is simply closed to achieve a watertight seal. The pathologic diagnosis was metaplastic (osseous) meningioma. Almost full recovery of the neurologic deficit was attained. Neither complication nor tumor recurrence has occurred in the 5 years since surgery. Dural preservation during surgical resection of spinal meningioma obviates the need for dural reconstruction and should reduce surgical morbidity. However, the patient should be followed long-term to watch for recurrence.
Dural preservation; Elderly; Lumbar spinal meningioma; Minimally invasive; Surgical treatment
Eel calcitonin (elcatonin) injection is widely used for elderly patients suffering from somatic pain in Japan. However, there have been few reports on the analgesic effects of elcatonin injection. The purpose of this study was to examine the analgesic effects of elcatonin injection in postmenopausal women with lower back pain.
This study was designed as a double-blind, randomized, placebo-controlled study. Thirty-six women aged ≥50 years with acute lower back pain participated in this study. They were randomly divided into two treatment groups according to whether they received a placebo or a weekly trigger point injection of elcatonin (20 units). They were observed for 5 weeks and the extent of pain at motion and at rest according to the visual analog scale (VAS) was evaluated. The mean VAS scores for the elcatonin group were then compared with those of the placebo group.
There were no statistically significant differences in the mean VAS scores for pain at rest between the two groups during the 5-week treatment course. However, the mean VAS scores for motion pain in the elcatonin group were significantly lower than those in the placebo group at the third, fifth and sixth weeks.
Elcatonin injection (20 units) significantly relieved motion pain in the lower back in postmenopausal women after three weeks of treatment. This analgesic effect continued for the subsequent 3 weeks.
Postmenopause; back pain; anti-nociceptive.
Different perforation rates for cervical pedicle screws by disease are expected in relation to bone quality and pedicle morphology; however, no report comparing pedicle screw perforation rate by disease had previously been published. This study investigated the perforation rates of pedicle screws inserted to cervical pedicle by disease and vertebral level using a CT-based navigation system.
Fifty-three patients who underwent cervical pedicle screw insertion using CT based navigation system were studied. Diseases included rheumatoid arthritis (RA) (24 cases), destructive spondyloarthropathy (DSA) (10), cervical spondylotic myelopathy (CSM) (9), spine tumor (6), and cervical spondylotic myelopathy associated with athetoid cerebral palsy (CP) (4). Screw perforation rates for cervical pedicle screws were studied. Major perforation was defined as perforation 50% of screw diameter or more.
Major perforation rate by disease from C3 to C7 was as follows: spine tumor (0/24, 0%), RA (2/59, 3.4%), DSA (3/65, 4.6%), CP (2/20, 10.0%), and CSM (6/40, 15.0%). There were no clinically important complications such as vertebra arterial injury, spinal cord injury, or nerve root injury caused by any screw perforation. Major perforation rate by vertebral level was: C2(2/30, 6.7%), C3(4/49, 8.2%), C4(6/43, 14.0%), C5(1/32, 3.1%), C6(1/41, 2.4%), and C7(1/45, 2.2%), showing highest rate for C4, followed by C3.
Cervical pedicle screw perforation rate by disease was higher in CSM compared to RA and DSA. The perforation rate by vertebral level was higher for C4 and C3, in this order.
Cervical pedicle screw; image guidance; perforation rate.
One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of “chiral impulse” as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds.
chirality; circularly polarized light; amino acids; solid films; synchrotron radiation; free electron laser; origin of terrestrial homochirality
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.
Cervical spine; Image guidance; Rheumatoid arthritis; Cervical pedicle screw; Transarticular screw
Lead intake from possible exposure routes among children residing in the Tokyo Metropolitan Area was estimated.
Lead concentrations in house dust samples collected from the houses of the children and those in 24-h duplicate diet samples of the children were determined. The daily lead intake was estimated by multiplying the lead concentrations in the house dust, diet, soil and ambient air (the latter two were from the literatures) by the corresponding intake and/or inhalation rates, and summing all of the products. Bioaccessibility tests were performed on the house dust, soil and diet samples to determine the lead uptake level.
Children residing in the Tokyo Metropolitan Area were estimated to be exposed to 21.5 μg of lead on a daily basis, with a maximum intake of up to 70.4 μg. The average weekly intake per kg body weight for a 5-year-old Japanese child was found to be 8.0 μg/kg bw/wk, which is below the Provisional Tolerable Weekly Intake (PTWI) of 25 μg/kg bw/wk. However, the maximum weekly intake was found to be 26 μg/kg bw/wk.
House dust and soil ingestion can be the predominant routes of exposure to lead among children in Japan, and the source(s) of lead in such media must be specified to reduce the lead intake level of the children.
lead intake; soil; house dust; diet; estimated blood lead
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.