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Biomedical subjects

Y Nakajima

Publications and source records attributed to Y Nakajima.

At least 73 records · Page 4Linked to original sources

Light-induced phase-delay of the chicken pineal circadian clock is associated with the induction of cE4bp4, a potential transcriptional repressor of cPer2 gene.

The chicken pineal gland contains the autonomous circadian oscillator together with the photic-input pathway. We searched for chicken pineal genes that are induced by light in a time-of-day-dependent manner, and isolated chicken homolog of bZIP transcription factor E4bp4 (cE4bp4) showing high similarity to vrille, one of the Drosophila clock genes. cE4bp4 was expressed rhythmically in the pineal gland with a peak at very early (subjective) night under both 12-h light/12-h dark cycle and constant dark conditions, and the phase was nearly opposite to the expression rhythm of cPer2, a chicken pineal clock gene. Luciferase reporter gene assays showed that cE4BP4 represses cPer2 promoter through a E4BP4-recognition sequence present in the 5'-flanking region, indicating that cE4BP4 can down-regulate the chick pineal cPer2 expression. In vivo light-perturbation studies showed that the prolongation of the light period to early subjective night maintained the high level expression of the pineal cE4bp4, and presumably as a consequence delayed the onset of the induction of the pineal cPer2 expression in the next morning. These light-dependent changes in the mRNA levels of the pineal cE4bp4 and cPer2 were followed by a phase-delay of the subsequent cycles of cE4bp4/cPer2 expression, suggesting that cE4BP4 plays an important role in the phase-delaying process as a light-dependent suppressor of cPer2 gene.

Amino Acid Sequence↗

Two isoforms of a member of the arthropod defensin family from the soft tick, Ornithodoros moubata (Acari: Argasidae).

We previously purified and determined the partial amino acid sequence of a 4 kDa peptide having high homology with scorpion defensin from the hemolymph of adult fed female soft ticks, Ornithodoros moubata. In this study, the full length sequences of two defensin isoforms were obtained. Deduced amino acid sequences reveal a precursor protein of 73 amino acid residues with a mature portion consisting of 37 amino acid residues. This mature peptide contains six cysteine residues conserved in the same location as other invertebrate defensins. Phylogenetic analysis reveals that Ornithodoros defensin is most closely related to scorpion defensin and other more ancient arthropods. Ornithodoros defensin mRNA is constitutively expressed and up-regulated by blood-feeding and bacterial injection. Ornithodoros defensin gene expression occurs mainly in the midgut. This is the first report of the cloning and gene expression of an antibacterial peptide from the Acari.

Amino Acid Sequence↗

Effects of electrical stimulation of the sciatic nerve on background electromyography and static stretch reflex activity of the trunk muscles in rats: possible implications of neuronal mechanisms in the development of sciatic scoliosis.

STUDY DESIGN: The effects of electrical stimulation of the sciatic nerve on background electromyographic and static stretch reflex activity of the trunk muscles were studied. OBJECTIVES: To verify the hypotheses that sciatic scoliosis is induced reflexively by radiculopathic pain, and that scoliosis might be maintained by prolonged asymmetric alteration of the trunk muscle tonus caused by central sensitization of the spinal neurons that constitute the postural reflex pathways. SUMMARY OF BACKGROUND DATA: Sciatic scoliosis usually occurs with convexity to the side of the herniated disc. The neuronal mechanism of sciatic scoliosis has not been well clarified. Recently, prolonged alteration of motor function in the hindlimbs of animals caused by central sensitization has been reported. METHODS: In spinalized rats (transection of the spinal cord), the sciatic nerve was stimulated electrically as a conditioning stimulus. Muscle stretch elicited by bending of the lumbar spine was applied as a test stimulus. Background and stretch reflex activities of the bilateral oblique abdominal, psoas, and quadratus lumborum muscles were recorded. Rats in which MK-801, an N-methyl-d-aspartate antagonist, was preadministered also were used. RESULTS: The conditioning stimulus enhanced background electromyographic activity in bilateral oblique abdominal, contralateral psoas, and quadratus lumborum muscles. Furthermore, the conditioning stimulus induced prolonged facilitation and depression of stretch reflex activity of the contralateral psoas and quadratus lumborum, and ipsilateral psoas and quadratus lumborum muscles, respectively. Preadministration of MK-801 reduced these excitatory and inhibitory effects. CONCLUSION: It was found that the pattern of electromyographic activity of the trunk muscles evoked by sciatic nerve stimulation coincided with the typical direction of sciatic scoliosis in patients with lumbar disc herniation. It was supposed that the prolonged asymmetric alteration of the trunk muscle tonus was caused by central sensitization, and that central sensitization of spinal neurons may underlie the neuronal mechanism of sciatic scoliosis.

Animals↗

Comparison of three-dimensional contrast-enhanced magnetic resonance angiography and axial radiographic angiography for diagnosing congenital stenoses in small pulmonary arteries.

Accuracy of 3-dimensional contrast-enhanced magnetic resonance angiography (MRA) in diagnosing morphology of the branch pulmonary artery (PA) was evaluated in 73 patients (aged 7.2 +/- 6.4 years [mean +/- SD]) with various congenital heart diseases. The presence or absence of localized stenosis of branch PAs, PA diameter, and Nakata's PA index were determined on MRA and axial radiographic angiography, and the results were compared. Sensitivity, specificity, and overall accuracy in detecting branch PA stenoses were 92.7%, 96.2%, and 95.2%, respectively. Correlations between axial radiographic angiography and MRA were excellent in measuring PA diameter (r = 0.956, SEE = 1.49 mm, n = 139) as well as PA index (r = 0.839, SEE = 48.9, n = 37); both p < 0.0001. Bland-Altman plots showed a mean difference +/- SD for PA diameter of 0.17 +/- 1.51 mm and for PA index of 8.5 +/- 50.1. When the main right and left PAs were taken as the first generation, the most distal branches visible on MRA were the 4.7 +/- 0.7 generation with breath-holding (n = 23) and the 3.7 +/- 0.5 without breath-holding (n = 50), respectively (p < 0.0001). Both intra- and interobserver variabilities of MRA measurements were few (9.5 +/- 11.6% and 13.5 +/- 15.0%, respectively, n = 139). In conclusion, 3-dimensional contrast-enhanced MRA enables us to document branch PA morphology clearly in infants and adult patients with congenital cardiovascular defects.

Adolescent↗

Interaction sites of the G protein beta subunit with brain G protein-coupled inward rectifier K+ channel.

G protein-coupled inward rectifier K(+) channels (GIRK channels) are activated directly by the G protein betagamma subunit. The crystal structure of the G protein betagamma subunits reveals that the beta subunit consists of an N-terminal alpha helix followed by a symmetrical seven-bladed propeller structure. Each blade is made up of four antiparallel beta strands. The top surface of the propeller structure interacts with the Galpha subunit. The outer surface of the betagamma torus is largely made from outer beta strands of the propeller. We analyzed the interaction between the beta subunit and brain GIRK channels by mutating the outer surface of the betagamma torus. Mutants of the outer surface of the beta(1) subunit were generated by replacing the sequences at the outer beta strands of each blade with corresponding sequences of the yeast beta subunit, STE4. The mutant beta(1)gamma(2) subunits were expressed in and purified from Sf9 cells. They were applied to inside-out patches of cultured locus coeruleus neurons. The wild type beta(1)gamma(2) induced robust GIRK channel activity with an EC(50) of about 4 nm. Among the eight outer surface mutants tested, blade 1 and blade 2 mutants (D1 and CD2) were far less active than the wild type in stimulating GIRK channels. However, the ability of D1 and CD2 to regulate type I and type II adenylyl cyclases was not very different from that of the wild type beta(1)gamma(2). As to the activities to stimulate phospholipase Cbeta(2), D1 was more potent and CD2 was less potent than the wild type beta(1)gamma(2). Additionally we tested four beta(1) mutants in which mutated residues are located in the top Galpha/beta interacting surface. Among them, mutant W332A showed far less ability than the wild type to activate GIRK channels. These results suggest that the outer surface of blade 1 and blade 2 of the beta subunit might specifically interact with GIRK and that the beta subunit interacts with GIRK both over the outer surface and over the top Galpha interacting surface.

Adenylyl Cyclases↗

Down-regulation of Pim-1 and Bcl-2 is accompanied with apoptosis of interleukin-6-depleted mouse B-cell hybridoma 7TD1 cells.

Here we report, interleukin-6 (IL-6) dependent mouse B-cell hybridoma, 7TD1 cells underwent apoptotic cell death with the starvation of IL-6. First, 7TD1 cells cultured without IL-6 arrested at G0/G1 phase (maximum accumulation at 24 h ) of the cell cycle. After that, the parameters of apoptosis namely, decreased mitochondrial transmembrane potential (DeltaPsi(m)), activation of caspases, DNA fragmentation and morphological changes (condensed nucleus and formation of apoptotic bodies) were observed. As evidents by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses, down-regulation of Pim-1 (a serine/threonine kinase) and Bcl-2 was observed in the IL-6-depleted 7TD1 cells. There was no change in the expression of c-Myc, Bcl-xL and Mcl-1, even at 48 h of IL-6-depletion. Taken together, these results indicate that IL-6 withdrawn from the 7TD1 cells resulted in G0/G1 arrest and then caspase-dependent apoptosis via mitochondrial pathway by down-regulation of Pim-1 and Bcl-2, which may be essential for anti-apoptotic signals of IL-6.

Animals↗

Accuracy evaluation of surface-based registration methods in a computer navigation system for hip surgery performed through a posterolateral approach.

OBJECTIVE: Many computer navigation systems have recently been developed for brain surgery, and the use of such systems in orthopedic surgery is increasing. Intraoperative registration of preoperative images is one of the most important steps in controlling the overall accuracy of computer navigation systems. Various parameters, such as CT-scan slice thickness, reconstruction pitch, intraoperative data sampling area, and data sampling volume, may affect the accuracy of registration. The purpose of this study was to evaluate the effect of the aforementioned parameters on the accuracy of registration for hip surgery performed through a posterolateral approach, and to find a clinically suitable trade-off between accuracy and surgical invasiveness. MATERIALS AND METHODS: One cadaveric pelvis and one cadaveric femur were used for this study. Four alumina ceramic balls with a diameter of 28 mm and within 1 micrometer of sphericity were attached to the pelvis, and three similar balls attached to the femur, to determine relative position. CT-scan images of the pelvis and femur were obtained with a helical scanner. Three sets of slice thickness and slice pitch were chosen for data acquisition, and two additional sets of reconstructed data were made. Bone contours were extracted by cutting out the surrounding substrate at a given CT number threshold, and surface models of the bone were made from the resultant data. The positions of the pelvis and femur were tracked by LED markers attached to the bone using an optical three-dimensional position sensor (OPTOTRAK). Registration of the computer models to the real objects was performed by measuring the position of a certain number of surface points on each object with an OPTOTRAK pen-probe. RESULTS AND CONCLUSION: Slice thickness and reconstruction pitch affected the accuracy of registration. As the sampling area was expanded from the periarticular area to the distant peripheral area, accuracy increased slightly. Accuracy did not increase when the whole area was used, but in fact decreased, especially in the femur. The positive effect of increasing the number of sampling points was saturated at 30 points when the surface of the periarticular area was sampled. The following trade-off between accuracy and invasiveness, in terms of various parameters of preoperative and intraoperative data, is proposed as clinically optimal: perform the CT scan with 3-mm slice thickness and 1-mm reconstruction pitch, and sample the periarticular area with 30 sampling points. With these parameters, the accuracy of registration was 1.2 mm and 0.9 degrees of bias with 0.7 mm and 0.3 degrees of RMS in the pelvis, and 1.4 mm and 0.6 degrees of bias with 1.3 mm and 0.3 degrees of RMS in the femur.

Cadaver↗

Bcl-X expression in esophageal squamous cell carcinoma: association with tumor progression and prognosis.

BACKGROUND AND OBJECTIVES: Bcl-2 family proteins are regulators of programmed cell death and important in the development and progression of human various tumors. The role of these proteins in the development, progression and differentiation of esophageal squamous cell carcinoma (ESCC) is unclear. METHODS: We investigated the expression of Bcl-2, Bcl-X, and Bax using immunohistochemistry in 86 ESCCs, and scored the expression by the weighted score. RESULTS: Bcl-2 expression related to pT category (P=0.043) and histological grade (P = 0.001). Bcl-X expression related to pT category (P = 0.003), pN category (P = 0.041) and the number of positive nodes (P = 0.036), and had a tendency to relate to histological grade (P = 0.086). Bax expression had a tendency to relate to pN category (P = 0.081). The inverse relationship between Bcl-2 and Bcl-X expression was detected (P = 0.001), while the positive one between Bcl-X and Bax expression was detected (P = 0.014). Patients with low Bcl-X weighted score had a significantly longer survival compared with those with high Bcl-X weighted score. Multivariate analysis revealed Bcl-X expression as the independent prognostic factors (P = 0.022). CONCLUSION: These results imply that Bcl-2 family proteins, especially Bcl-X, may contribute to the progression in ESCC.

Adult↗

Cost-effectiveness associated with the diagnosis and staging of non-small-cell lung cancer.

OBJECTIVE: We evaluated how much time and money could be saved without compromising overall results in treating lung cancer. SUBJECTS AND METHODS: We retrospectively evaluated 318 patients for T- and M-factors and 335 for N-factor. If bronchoscopy failed to diagnose a mass lesion believed to be malignant in x-ray computed tomography (CT), we proceeded to direct thoracotomy without needle or video-assisted biopsy. When mediastinal nodes were negative in CT, we proceeded to direct thoracotomy without mediastinoscopy. We searched routinely for distant metastasis with brain and abdominal CTs and bone scans. RESULTS: Lesions suspected of malignancy in CT were pathologically malignant in 93%. A total of 82.8% of patients with CT-negative mediastinum were without metastasis. The remainder, with metastasis, had a postoperative 5-year survival of 23.5%. Brain CT scans were positive in only 2.2%, abdominal CT scans in 2.4%, and bone scans in 5.0%, for patients with a cT1/T2 non-cN2 lesion. CONCLUSION: Brain and abdominal CT scans and bone scans may be omitted for cT1/T2 and non-cN2 lesions in CT. CT-negative mediastinum then leads to direct thoracotomy. The vast majority of patients may thus undergo surgery earlier with less physical and financial burden. The cost saving was calculated to be 59.4% per cT1/T2 non-cN2 patient, or US$666,815, for population evaluated based on cost-effectiveness.

Adult↗

Intragraft expression of p38 and activated p38 MAPK (mitogen-activated protein kinase) in rat small bowel transplantation.

Recent studies suggest that cytotoxic T-lymphocytes expressing p38 mitogen-activated protein kinase (p38MAP kinase) contribute to allograft rejection in clinical heart transplantation. Interleukin-2 (IL-2), a potent T cell mitogen, activates the p38MAP kinase pathway, resulting in phosphorylation of target transcription factors. In this study we investigated the expression of activated p38MAP kinase in intragraft cell infiltrates following rat heterotopic small bowel transplantation and examined the effects of the immunosuppressant FK506 on intragraft expression of activated p38MAP kinase and allograft rejection. Allografts receiving FK506 (0.5 mg/kg per day i. m.) for 7 days as primary anti-rejection therapy had a significant reduction in histopathological evidence of allograft rejection on Day 7, compared to allograft controls. In addition, Western blotting analysis of intragraft cell infiltrates showed a reduction in the expression of activated p38MAP kinase in allografts treated with FK506. We conclude that intragraft cell infiltrate expression of activated p38MAP kinase is an important marker of acute rejection in this animal model of small bowel transplantation, and that FK506 is an effective immunosuppressant, in this situation, that may act in part by preventing the activation of p38MAP kinase.

Animals↗

Heat stress results in incomplete C-to-U editing of maize chloroplast mRNAs and correlates with changes in chloroplast transcription rate.

The editing status rps14 and rpl20 mRNAs decreased rapidly from nearly 100% edited to about 30% edited when maize plants were shifted from 20 degrees C to 37 degrees C. A decrease in the extent of editing was easily detected within 2 h and decreased to a steady-state level of about 40% C-to-U conversion at 37 degrees C. In contrast, the editing status of these chloroplast mRNAs increased relatively slowly after plants were shifted from 37 degrees C to 20 degrees C. Chloroplasts isolated from maize plants which were grown at 20 degrees C and then shifted to 37 degrees C for 24 h were 5-10 times more transcriptionally active than chloroplasts isolated from maize plants grown continuously at 20 degrees C. Thus, the high transcription rate at 37 degrees C may establish a kinetic condition where the rate of transcription exceeds the capacity of the editing apparatus and results in incomplete editing.

Chloroplasts↗

Lesser sac hematoma as a sign of rupture of hepatocellular carcinoma in the caudate lobe.

The purpose of this study was to evaluate the CT findings of rupture of hepatocellular carcinoma (HCC) in the caudate lobe of the liver. The CT scans of five cases of rupture of HCC in the caudate lobe of the liver were retrospectively reviewed and correlated with clinical records. All cases showed exophytic tumors in the caudate lobe of the liver and high-attenuation hematomas in the lesser sac on CT. A lesser sac hematoma may be a sentinel clot sign of rupture of HCC in the caudate lobe.

Aged↗

High dorsal drainage routes of Spiegel's lobe.

BACKGROUND/PURPOSE: The venous drainage from Spiegel's lobe to the terminal portion of the hepatic veins has been described in the literature, but its morphology remains unclear. METHODS: We examined 42 dissected liver specimens and 38 cast specimens. RESULTS: In 8 of the 42 dissected liver specimens and 5 of the 38 cast specimens we found atypical but thick (over 3 mm) caudate veins that drained Spiegel's lobe and emptied into the terminal portion (along the most proximal 5-mm course) of the middle hepatic vein (MHV) or the inferior vena cava (IVC) near the MHV terminal (less than 10 mm from the MHV). We termed these the superior caudate vein. This vein ran upward between the caudate portal branches of the left and hilar bifurcation origins or through the territory of the left origin. The superior caudate vein, consistently coexisted with the typical vein(s). We also found several analogues of the superior caudate vein, such as the cranially shifted opening of the typical caudate vein and relatively thick proximal tributaries of the MHV from Spiegel's lobe. CONCLUSIONS: Although the superior caudate vein, if present, seemed to have a large role in the venous drainage of the lobe, its incidence seemed to be too low for clinical relevance.

Cadaver↗

Multiple primary cancers associated with esophageal carcinoma.

This study was conducted to examine the characteristics of esophageal cancers with primary synchronous or metachronous cancer in another organ. We retrospectively evaluated 744 patients who underwent esophagectomy for esophageal cancers between 1985 and 1998. The patients were divided into two groups according to whether they had multiple primary cancer (MPC) or nonmultiple primary cancer (NPC). Stage I cancer was significantly more frequent among patients with MPC than among those with NPC (P < 0.0001). Among patients with MPC, another primary cancer was found in the head and neck region in 70 (42.4%), in the stomach in 51 (30.9%), and in the colon, lung, breast, and other locations in the remaining patients. Of the 70 patients with another primary cancer in the head and neck region, 32 (45.7%) had pharyngeal cancer. Furthermore, the incidence of intraesophageal multiple cancer in the patients with primary cancer in the head and neck region was significantly higher than that in those whose other primary cancers were gastric cancer or in those with NPC (P = 0.0135. P < 0.0001). The 5-year survival rate of the patients with MPC was 51.28%, which was significantly higher than that of those with NPC (P = 0.019). In conclusion, a better knowledge of the relationships between esophageal carcinoma and cancers in other organs may lead to earlier detection of other primary cancers and improved therapeutic results.

Carcinoma, Squamous Cell↗

Ileal adenomyoma accompanied by primary peritonitis: report of a case.

We report herein the case of a 52-year-old woman who presented with severe abdominal pain and a 2-week history of a yellow vaginal discharge. An emergency operation was performed for localized peritonitis attributed to acute perforated appendicitis. There were no findings to indicate the cause of peritonitis, but by chance, a submucosal tumor was found in the ileum 2m from Bauhin's valve. Appendectomy and wedge resection of the ileum with the submucosal tumor were carried out. The peritonitis was considered to have been idiopathic from bacterial and molecular biological examination of the ascites. Pathological, immunohistochemical, and flow cytometrical findings of the resected ileal submocosal tumor indicated a diagnosis of ileal adenomyoma with no malignancy, which suggested metaplasia of the pancreaticobiliary to gastric epithelium.

Adenomyoma↗

Pneumoperitoneum following the spontaneous rupture of a gas-containing pyogenic liver abscess: report of a case.

We report herein the case of a ruptured liver abscess that resulted in pneumoperitoneum. A patient with diabetes mellitus presented with symptoms of acute abdomen. The plain abdominal radiograph and computed tomography findings revealed abdominal free air and a gas-containing liver abscess, whereby a diagnosis of a ruptured liver abscess was made. An emergency operation was performed, and the abscess was drained followed by peritoneal lavage and the administration of appropriate antibiotics. To the best of our knowledge, very few cases of spontaneous pneumoperitoneum occurring secondary to the rupture of a gas-containing liver abscess have been encountered in Japan.

Anti-Bacterial Agents↗

Amyloid precursor protein associates independently and collaboratively with PTB and PDZ domains of mint on vesicles and at cell membrane.

The mint family consists of evolutionarily conserved adapter proteins from Caenorhabditis elegans to mammalian neurons. Three mammalian isoforms, mint1, 2, and 3, are extensively diverted in their N-terminal halves and, in striking contrast, are highly homologous to each other in their C-terminal halves containing phosphotyrosine-binding (PTB) and PSD-95/DLG-A/ZO-1 (PDZ) domains that work as protein-protein interaction modules. Biochemical and genetic analyses revealed that mint1 and LIN-10, a homolog in C. elegans, comprise macromolecular complexes in the presynaptic and postsynaptic terminals, thereby bringing synaptic vesicles to the exocytotic transmitter release site and localizing receptors and ion channels in the specific membrane domains. Amyloid precursor protein is one of the targets of the PTB domain of mint and this interaction modulates its proteolytic procedures ending up with amyloid beta peptide production, but its molecular mechanism is unclear. We show by an in situ hybridization technique that mint3, a ubiquitous isoform, is expressed both in polar cells like neurons, and in non-polar cells, such as glia and ependymal cells, in the mouse brain. In addition, a considerable amount of a human homolog mint3 (approximately 70 kDa) was expressed in a human epithelial cell line. Subcellularly, mint3 is specifically enriched in vesicles in the cytoplasm, cell membrane, and Golgi complex as reserves. A series of deletions or site-directed mutations revealed that mint3 double recognizes an amyloid precursor protein-containing macromolecular complex via the PTB and PDZb domains independently and cooperatively, not only in the cytoplasmic transporting vesicles but even after amyloid precursor protein was targeted and/or inserted to the specific cell membrane domains. From these results we suggest that mint3 links amyloid precursor protein to other components, thereby regulating its transport, endocytosis, and metabolism. Abnormal metabolism of amyloid precursor protein causes an early-onset type of Alzheimer's disease but its molecular mechanism is incompletely understood. The present findings give morphological evidence and a molecular framework of how mint interacts with amyloid precursor protein and modifies its processing on the secretory pathway.

Adaptor Proteins, Signal Transducing↗