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Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 127 records · Page 7Linked to original sources

Arch-first reconstruction via median sternotomy. Short retrograde cerebral perfusion.

In December 1998, we introduced arch-first reconstruction for total aortic arch replacement via conventional median sternotomy in order to shorten the duration of retrograde cerebral perfusion (RCP). We used a separate straight graft for an elephant trunk, which allowed an easy subsequent distal anastomosis. The average RCP duration in this series was 32.1+/-5.8 min (mean+/-SD, range, 24-40 min, n=12), which was significantly shorter (p<0.05) than that of the conventional procedure (45.6+/-12.4 min, range, 34-65 min, n=8), in which we first perform a distal anastomosis. No significant differences in cardiopulmonary bypass time (268+/-81 min vs 258+/-42 min) nor operation time (518+/-213 min vs 517+/-82 min) between the two groups were observed. There was no hospital death in either group. One patient in the second series (conventional method) suffered temporary neurological disturbance. For acceptable RCP duration, total aortic arch replacement is currently the standard procedure in our institution for Stanford A type aortic dissection.

Anastomosis, Surgical↗

New visual acuity chart for patients with macular hole.

PURPOSE: To evaluate the usefulness of a new multiple-letter visual acuity chart (MLAC) for the measurement of visual acuity in patients with macular hole. METHODS: Visual acuity was measured using a standard visual acuity chart (Landolt rings, also referred to as C's) and with the MLAC in normal subjects and in patients with a cataract or a macular hole. The MLAC has 14 plates (45 x 45 cm), and on one plate, many Landolt C's were printed with the gaps pointing in the same direction and all of one size. The sizes of the letters and gaps were made to give equivalent visual acuities of 0.1, 0.15, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.5, and 2.0. The spacing between the letters was 33.3% of the diameter of the C's. Each chart projected many C's onto the macular area (5 degrees x 5 degrees ), which permitted the measurement of visual acuity at an extrafoveal point without the patient having to search for the extrafoveal point with the best acuity. RESULTS: There was no difference in the acuity measurement determined with the standard chart and the MLAC in normal subjects and patients with cataracts. Twelve of 16 patients with open macular hole, however, demonstrated higher acuity measurement (more than two lines) on the MLAC than on the standard chart. The improvement of visual acuity measurement after successful macular hole surgery was significantly less with the MLAC than with the standard chart. CONCLUSIONS: Our results suggest that the standard acuity chart, when administered before surgery, underestimates the patient's potential visual acuity after surgery, whereas the MLAC provides a better estimate of the patient's postoperative acuity. The MLAC can be a useful tool for measuring visual acuity in patients with macular hole.

Aged↗

[Novel biodegradable materials for drug delivery systems (DDS)].

The authors provide three new and different types of fibrin gels (FCs) and a chitosan sheet (BC) using an ultraviolet (UV)-crosslinking method. They are 1) FC-UV, 2) gelatin entrapped FC; FC (Gp)-UV, 3) chitosan entrapped FC; FC (Cs)-UV and 4) BC-UV. Each material was loaded with aqueous cis-platinum (CDDP), and both the degradation of the drug carriers and the release profile of the CDDP were examined in vitro. The FCs, 1)-3), gradually degraded and dissolved within 10-12 days. The BC, 4), maintained its original weight for more than 30 days. Each FC showed a sustained release of CDDP for 10 days, while BC provided an initial bursting of the loaded drug. New materials 2) and 3) show great potential as drug carriers for DDS and further in vivo studies are now proceeding.

Biodegradation, Environmental↗

Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.

The metabotropic glutamate receptors (mGluRs) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. Here we have determined three different crystal structures of the extracellular ligand-binding region of mGluR1--in a complex with glutamate and in two unliganded forms. They all showed disulphide-linked homodimers, whose 'active' and 'resting' conformations are modulated through the dimeric interface by a packed alpha-helical structure. The bi-lobed protomer architectures flexibly change their domain arrangements to form an 'open' or 'closed' conformation. The structures imply that glutamate binding stabilizes both the 'active' dimer and the 'closed' protomer in dynamic equilibrium. Movements of the four domains in the dimer are likely to affect the separation of the transmembrane and intracellular regions, and thereby activate the receptor. This scheme in the initial receptor activation could be applied generally to G-protein-coupled neurotransmitter receptors that possess extracellular ligand-binding sites.

Amino Acid Sequence↗

Cryptic dimer interface and domain organization of the extracellular region of metabotropic glutamate receptor subtype 1.

Previously, we produced the whole extracellular region of metabotropic glutamate receptor subtype 1 (mGluR1) in a soluble form. The soluble receptor retained a ligand affinity comparable with that of the full-length membrane-bound receptor and formed a disulfide-linked dimer. Here, we have identified a cysteine residue responsible for the intermolecular disulfide bond and determined domain organization of the extracellular region of mGluR1. A mutant, C140A, was a monomer under nonreduced conditions by SDS-polyacrylamide gel electrophoresis; however, C140A was eluted at the position similar to that of mGluR113, the wild type soluble receptor, by size exclusion column chromatography. Furthermore, C140A bound a ligand, [(3)H]quisqualate, with an affinity similar to that obtained by mGluR113. Oocytes injected with RNA for full-length mGluR1 containing C140A mutation showed responses to ligands at magnitudes similar to those with wild type full-length RNA. Thus, elimination of the disulfide linkage did not perturb the dimer formation and ligand signaling, suggesting that cryptic dimer interface(s) possibly exist in mGluR1. Limited proteolysis of the whole extracellular fragment (residue 33-592) revealed two trypsin-sensitive sites, after the residues Arg(139) and Arg(521). A 15-kDa NH(2)-terminal proteolytic fragment (residue 33-139) was associated with the downstream part after the digestion. Arg(521) was located before a cysteine-rich stretch preceding the transmembrane region. A new shorter soluble receptor (residue 33-522) lacking the cysteine-rich region was designed based on the protease-sensitive boundary. The purified receptor protein gave a K(d) value of 58.1 +/- 0.84 nm, which is compatible to a reported value of the full-length receptor. The B(max) value was 7.06 +/- 0. 82 nmol/mg of protein. These results indicated that the ligand-binding specificity of mGluR1 is confined to the NH(2)-terminal 490-amino acid region of the mature protein.

Alanine↗

Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines.

In a recent study, we identified frequent amplification of DNA copy number at chromosome 9p23-24 in cell lines derived from esophageal squamous cell carcinomas (ESCs), using comparative genomic hybridization. Because amplified regions often harbor oncogenes and/or other tumor-associated genes, and because 9p23-24 amplification had been reported in various other types of cancers, we used fluorescence in situ hybridization and Southern blot analysis to map the 9p23-24 amplicon. We then screened target genes/transcripts present within this amplicon by Northern blotting. With this strategy, we successfully cloned a novel gene, designated gene amplified in squamous cell carcinoma 1 (GASC1), that was amplified and overexpressed in several ESC cell lines. The deduced amino acid sequence of GASC1 contains two PHD-finger motifs and a PX domain. PHD-finger motifs are found in nuclear proteins that participate in chromatin-mediated transcriptional regulation and are present in a number of proto-oncogenes. Our findings suggest that overexpressed GASC1 may play an important role in the development and/or progression of various types of cancer including ESC.

Amino Acid Sequence↗

Application of PET-MRI registration techniques to cat brain imaging.

UNLABELLED: In positron emission tomography (PET) studies of diseased animals, it is very useful to have accurate anatomical information as a reference. In human studies, anatomical information is usually obtained from magnetic resonance imaging (MRI) of the subject with retrospective registration of the subject's PET image to the MRI. A number of PET-MRI registration techniques are used for this purpose. However, the utility of these methods has not been tested for animals image registration. This paper studies the feasibility of applying two currently used human brain PET-MRI registration techniques to cat brain images. METHODS: Three cats were anesthetized with isoflurane gas, and PET images were acquired with H(2)(15)O, benzodiazepine receptor ligand 11C-flumazemil (FMZ), dopamine receptor ligand 11C-nemonapride (NEM) and fluorodeoxy glucose (18F-FDG). The four PET scans were acquired consecutively within the same day while the cat remained fixed in the scanner. We also obtained T1-weighted and T2-weighted MRI of the cats in a 4.7 T unit. The PET images were registered to MRI using two human brain registration techniques: a semi-automatic method (SAM), which is a two-step method based on the extraction of the midsagittal plane, and an automatic method (AMIR) method that minimizes PET pixel variance within spatially connected segments determined by MRI. RESULTS: T2-weighted MRI provided better structural information than T1 MRI. FMZ did, while FDG or H(2)O PET images did not, provide a structural outline of the brain. The FMZ PET image was registered to MRI satisfactorily using SAM. The striatum visualized in nemonapride PET image re-sliced with the same parameters matched the striatum identified in T2-weighted MRI. Registration by AMIR was successful by inspection for FMZ, FDG or H(2)O PET images in only one of the three cats. The registration error of SAM was estimated to be less than 2 mm or 2 degrees. CONCLUSION: A satisfactory registration of FMZ-PET to T2-weighted MRI of the cat brain was obtained by a two-step manual registration technique. This will enhance the usefulness of PET in the field of cerebral pathophysiology.

Animals↗

Sensory innervation of the sacroiliac joint in rats.

STUDY DESIGN: The segmental levels of dorsal root ganglions innervating the sacroiliac joint in rats were investigated using the retrograde transport method. The pathways and functions of the nerve fibers supplying the sacroiliac joint were determined by immunohistochemical detection of transported tracer. OBJECTIVES: To study the sensory innervation of the sacroiliac joint and to elucidate the neural pathways of low back pain originating from the sacroiliac joint. SUMMARY OF BACKGROUND DATA: The sacroiliac joint is a possible source of low back pain. The L4-S4 spinal nerves have been regarded as the nerves innervating the sacroiliac joint in humans. However, the origins of nerve fibers have not been analyzed experimentally with tracer methods. METHODS: Cholera toxin B subunit, a neural tracer, was injected into the left sacroiliac joint of adult rats, and the bilateral dorsal root ganglions were immunohistochemically examined 4 days after injection. In another rat group, the dorsal root ganglions were examined using the same methods after resection of the left sympathetic trunk from L2 to the most caudal level. Thus, the pathways of the nerve fibers supplying the sacroiliac joint were investigated. RESULTS: Labeled neurons were mainly located in the ipsilateral dorsal root ganglions from L1 to S2 of the unsympathectomized rats and in the ipsilateral dorsal root ganglions from L4 to S2 of the sympathectomized rats. CONCLUSIONS: The sacroiliac joint was innervated by sensory neurons in dorsal root ganglions ipsilateral to the joint from L1 to S2. Sensory fibers from the L1 and L2 dorsal root ganglions passed through the paravertebral sympathetic trunk.

Adrenergic Fibers↗

Outcome of one-level posterior lumbar interbody fusion for spondylolisthesis and postoperative intervertebral disc degeneration adjacent to the fusion.

STUDY DESIGN: Review of the clinical and radiologic records of patients who underwent one-level posterior lumbar interbody fusion (PLIF) at L4-L5. OBJECTIVE: To determine whether adjacent intervertebral disc degeneration after PLIF affects the clinical results, and whether preoperative caudal disc (L5-S1) degeneration affects postoperative clinical results. SUMMARY OF BACKGROUND DATA: There is little reliable information in the literature regarding clinical results and adjacent disc degeneration after PLIF. METHODS: Forty-five patients who underwent L4-L5 PLIF for spondylolisthesis with more than 5 years of postoperative observation were included in this study. PLIF was performed in conjunction with posterior instrumentation. The posterior lumbar intervertebral grafting was performed using both autograft and a ceramic spacer. Intervertebral disc heights at L2-L3, L3-L4, and L5-S1 were measured before and after surgery. The patients were divided into two groups based on the presence or absence of the preoperative L5-S1 narrowing. Correlation between clinical status evaluated by the recovery rate of the Japanese Orthopedic Association (JOA) score and disc heights were determined. RESULTS: All intervertebral disc heights adjacent to the fusion decreased after surgery (P < 0.05). However, no significant correlation was seen between clinical results estimated by the recovery rate and postoperative disc narrowing. There was also no significant difference in clinical results between patients with or without preoperative L5-S1 narrowing. CONCLUSIONS: There is no evidence from the results that postoperative narrowing of the adjacent disc and preoperative narrowing of the L5-S1 disc affects the clinical outcome of L4-L5 PLIF.

Adult↗

Loss of fragile histidine triad gene expression is associated with progression of esophageal squamous cell carcinoma, but not with the patient's prognosis and smoking history.

BACKGROUND: Recently, fragile histidine triad (FHIT) gene abnormality has been thought to be associated with several malignancies and smoking history. The authors previously discovered that methylation of the 5' CpG island of the FHIT gene was closely associated with transcriptional inactivation in esophageal squamous cell carcinoma (SCC); however, the clinical impact of the FHIT gene in esophageal carcinoma is still unknown. METHODS: In this article, the authors evaluated the clinical impact of the FHIT gene in 149 esophageal squamous cell carcinoma (SCC) patients retrospectively using immunohistochemical analysis. They also examined the correlation between FHIT protein expression and smoking history. RESULTS: Among 149 curative resection (R0) cases of esophageal SCC, normal FHIT protein expression was noted in only 33 cases (22.1%), whereas reduced FHIT protein expression was noted in 67 cases and there was no FHIT expression in 50 cases. When a tumor invaded the muscle layer, FHIT protein expression was markedly reduced. The cases with reduction or loss of FHIT protein expression tended to have poor prognoses (P = 0.069). However, Cox multivariate analysis revealed that FHIT protein reduction had no relation to prognosis. FHIT protein expression had no relation to smoking history. CONCLUSIONS: FHIT protein expression was associated with progression of esophageal SCC, however, it may not be associated with the patient's prognosis and smoking history.

Aged↗

Functional analysis of the C-terminal region of recombinant human thrombopoietin. C-terminal region of thrombopoietin is a "shuttle" peptide to help secretion.

Thrombopoietin (TPO) is a cytokine that primarily stimulates megakaryocytopoiesis and thrombopoiesis. TPO has a unique C-terminal tail peptide of about 160 amino acids that consists mostly of hydrophilic residues and contains six N-linked sugar chains. In order to investigate the biological function of the C-terminal domain, two series of mutations were performed. One is systematic truncation from the C terminus. Another is elimination of N-glycosylation sites in the C-terminal domain by Asn to Gln mutations. After the mutant proteins were expressed by mammalian cells, it was found that the elimination of the N-linked sugar sites did not affect the biological activity, whereas truncation of the C-terminal domain resulted in elevation of in vitro activity up to 4-fold. The C-terminal peptide itself was found to inhibit the in vitro activity. Moreover, both the C-terminal truncation and the elimination of the N-glycosylation sites decreased the secretion level progressively down to (1)/(10) that of wild type, and the amount of the mutant left in the cell increased. The N-glycosylation in the C-terminal region was found to be important for secretion of TPO. Among six N-glycosylation sites in the C-terminal region, two locations, Asn-213 and Asn-234, were found to be critical for secretion, and two other locations, Asn-319 and Asn-327, did not affect the secretion.

Animals↗

The suppression of small GTPase rho signal transduction pathway inhibits angiogenesis in vitro and in vivo.

Angiogenesis consists of multistep pathways such as the degradation of the matrix, proliferation of the endothelial cells, motility of the endothelial cells, formation of the cord structure and network formation of microvessels. The small GTPase Rho participates in cell motility through actin fiber polymerization. The role of the small GTPase Rho signal transduction pathway in regulating angiogenesis, however, is still unknown. In this study, we investigated the role of the small GTPase Rho signal transduction pathway in angiogenesis in vitro and in vivo using the exoenzyme, Clostridium botulinum C3 transferase, which specifically suppresses Rho and a compound, Y-27632, which suppresses p160ROCK (Rho-associated coiled-coil containing protein kinase). In this paper, we showed that the small GTPase Rho-p160ROCK signal transduction pathway played an important role in angiogenesis both in vitro and in vivo. These results suggest that inhibition of the small GTPase Rho signal transduction pathway by the p160ROCK inhibitor could be a possible new strategy for angiogenic diseases.

Amides↗

Giant cauda equina schwannoma. A case report.

STUDY DESIGN: Case report. OBJECTIVES: To present a rare case of a giant schwannoma of the cauda equina. SUMMARY OF BACKGROUND DATA: Giant spinal schwannoma of the cauda equina, which involves many nerve roots, is rare and there is usually no ossification in the schwannoma. It is unknown whether or not complete excision is preferable if the tumor is located in the lumbar lesion. METHODS: A 57-year-old woman had a 10-year history of low back pain. Scalloping of the posterior surface of the vertebral bodies from L3 to the sacrum was found. Magnetic resonance imaging disclosed a giant cauda equina tumor with multiple cysts. Central ossification revealed by computed tomography and an unusual myelogram made the preoperative diagnosis difficult. RESULTS: The patient underwent incomplete removal of the tumor, decompression of cysts, and spinal reconstruction. The tumor was proved to be a schwannoma. The postoperative course was uneventful and she has been almost free from low back pain for 3 years and 4 months. CONCLUSIONS: Giant schwannoma in the lumbar spine region is usually excised incompletely, because complete removal had the risk of sacrificing many nerve roots. In spite of the incomplete removal of the tumor, the risk of recurrence is low.

Cauda Equina↗

Comparison of short inversion time inversion recovery (STIR) and fat-saturated (chemsat) techniques for background fat intensity suppression in cervical and thoracic MR imaging.

The purpose of this study was to compare short inversion time inversion recovery (STIR) fast spin-echo (FSE), and fat-saturated T2-weighted FSE sequences in terms of uniformity of fat suppression and lesion conspicuity for magnetic resonance (MR) imaging of the neck and thorax. STIR FSE and fat-saturated T2-weighted FSE images were scored for uniformity of fat suppression (n = 40) and lesion conspicuity (n = 35). Five-point rank score analyses were utilized by three experienced radiologists. The mean scores of STIR and fat-saturated FSE techniques for uniformity of fat suppression were 4.3 and 2.3, respectively (P < 0.0001). The mean scores of STIR and fat-saturated FSE techniques for lesion conspicuity were 4.2 and 3.5, respectively (P < 0.0001). Insufficient fat suppression was prominent in the mandible, supraclavicular region, anterior mediastinum, epipericardial fat, and subdiaphragmatic fat. In addition, fat-saturated T2-weighted FSE showed inadvertent water suppression in 25%. The STIR FSE technique was superior to the fat-saturated FSE technique for cervical and thoracic MR imaging.

Adolescent↗

Extract prepared from the bark of Cinnamomum cassia Blume prevents glutamate-induced neuronal death in cultured cerebellar granule cells.

We studied the protective effect of a water extract from the bark of Cinnamomum cassia Blume on glutamate-induced neuronal death by MTT assay and its action on (45)Ca(2+) influx using cultured rat cerebellar granule cells. In a dose-dependent manner, this extract (10(-5)-10(-4) g/mL) significantly protected against glutamate-induced cell death and also inhibited glutamate-induced (45)Ca(2+) influx. These results suggest that the bark of Cinnamomum cassia has a protective effect on glutamate-induced neuronal death through the inhibition of Ca(2+) influx.

Animals↗

Preclinical evaluation of [11C]SA4503: radiation dosimetry, in vivo selectivity and PET imaging of sigma1 receptors in the cat brain.

Our previous in vivo study with rats has demonstrated that 11C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([11C]SA4503) is a potential radioligand for mapping CNS sigmal receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [11C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [11C]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4503 and haloperidol, but not by co-injection of any of six ligands for sigma2 or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for signal receptor. In the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in the cortex and cerebellum at 76 min after tracer injection. We have concluded that [11C]SA4503 has the potential for mapping sigma1 receptor by PET.

Animals↗

Heart rate variability during massive hemorrhage and progressive hemorrhagic shock in dogs.

PURPOSE: To investigate the sequential changes in heart rate (HR), autonomic nervous activity presented by the spectral analysis of heart rate variability (HRV), hemodynamics and metabolism during massive hemorrhage and progressive hemorrhagic shock in dogs. METHODS: Twelve dogs were subjected to acute massive hemorrhage until mean arterial pressure (MAP) reached 50 mm Hg. Then bleeding was stopped and they were allowed to reach a plateau phase. They were divided, post hoc, into bradycardic or tachycardic groups according to their HR response to the acute massive hemorrhage. After reaching a plateau phase, the dogs were further bled to keep their MAP around 50 mmHg (progressive hemorrhagic shock). Their heart rate power spectra were quantified into low-frequency (LF) (0.04-0.15 Hz) and high-frequency (HF) (0.15-0.4 Hz) components. RESULTS: In the bradycardic group, both LF and HF increased after massive hemorrhage, but during progressive hemorrhagic shock these components decreased while HR increased. In the tachycardic group, LF increased after massive hemorrhage, but during progressive hemorrhagic shock LF decreased with continuous suppression of HF CONCLUSION: Massive hemorrhage caused two types of HR response: bradycardia and tachycardia. The HRV profile showed differential autonomic characteristics, and could be a valuable tool in assessing various degrees of hemorrhagic shock.

Animals↗