Biomedical subjects

K Nakajima

Publications and source records attributed to K Nakajima.

At least 163 records · Page 9Linked to original sources

PubMed2001

Phantom studies for estimation of defect size on cardiac (18)F SPECT and PET: implications for myocardial viability assessment.

UNLABELLED: SPECT with (18)F-FDG has emerged as an alternative to dedicated PET for the assessment of myocardial viability. However, whether FDG SPECT can reliably quantify the extent of viable and scarred myocardium is uncertain. The aim of this study was to investigate whether SPECT with an (18)F-labeled agent would provide information on defect size similar to that provided by dedicated PET. METHODS: Imaging was performed using an elliptic cylinder chest phantom with simulated bone, lung, mediastinum, liver, and heart. (18)F was administered into the myocardium, mediastinum, right and left ventricular cavities, and liver. Plastic inserts (n = 11) ranging in size from 2% to 60% of the myocardium were used to simulate transmural myocardial infarctions. The chest phantom was imaged with a dedicated PET camera and with a double-head SPECT camera equipped with ultra-high-energy collimators. Both SPECT and PET data were analyzed using a semiquantitative polar map approach. Defects were quantified using various cutoff thresholds ranging from 30% to 80% of peak activity and were expressed as a percentage of the left ventricular myocardium. Defect size as measured by SPECT or PET was compared with true defect size. RESULTS: The measured SPECT defect size was highly variable depending on the cutoff used, whereas PET defect size was relatively constant over the range of cutoffs tested. The mean absolute difference between measured and true defect sizes was minimal at a cutoff of 50% of peak activity for both SPECT (3.3% +/- 3.3%) and PET (2.7% +/- 2.5%). For this threshold, both SPECT and PET measurements showed an excellent correlation with true defect size (r = 0.98 for SPECT and 0.99 for PET). The correlation between SPECT and PET measurements was also excellent (r = 0.99; P < 0.01). CONCLUSION: If an appropriate threshold is used to define a defect, SPECT with an (18)F-labeled agent can accurately measure defect size similarly to the manner of PET.

Fluorodeoxyglucose F18↗

PubMed2001

Oxidative events cause degradation of apoB-100 but not of apo[a] and facilitate enzymatic cleavage of both proteins.

Lipoprotein [a] (Lp[a]) contains equimolar amounts of apoB-100 and apolipoprotein [a] (apo[a]). Both proteins are amenable to degradation in vivo by mechanisms yet to be clearly defined. In this study, we examined the in vitro susceptibility of LDL and Lp[a], obtained from the same donor, to oxidation by either Cu(2)+ or the combined Crotalus adamanteus phospholipase A2 and soybean lipoxygenase system, monitoring the course of the reaction by the generation of conjugated dienes and fatty acids. In some experiments, treatment with leukocyte elastase (LE) or matrix metalloproteinase 12 (MMP-12) was administered before and after the oxidative step. In the case of Lp[a] we found that with both oxidizing systems, conditions that caused the breakdown of apoB-100 did not degrade apo[a] although oxidation-mediated changes were detected in the latter by intrinsic tryptophan fluorescence spectroscopy. Similar results were obtained with a reassembled Lp[a] obtained by incubating free apo[a] with LDL. Both apo[a] and apoB-100 were cleaved by LE and MMP-12 but the enzymatic cleavage was more marked when the preoxidized proteins were used as a substrate. Taken together, our in vitro studies indicate that apo[a] but not apoB-100 resists oxidative fragmentation, whereas both proteins are cleaved by enzymes of the serine and metalloproteinase families. We speculate that the fragments of apo[a] observed in vivo may be preferentially generated by proteolytic rather than oxidative events, whereas apoB-100 can be degraded by both mechanisms.

Apolipoprotein B-100↗

PubMed2001

Bipedal locomotion by the normally quadrupedal Japanese monkey, M. Fuscata: strategies for obstacle clearance and recovery from stumbling.

This study explored how the normally quadrupedal Japanese monkey adjusts to treadmill perturbations, when trained to walk bipedally. The monkey was required to use the left hindlimb to clear an obstacle that was fixed on the left side of a treadmill belt. The monkey either cleared the obstacle (CL: cleared locomotion), or stumbled over it (SL: stumbled locomotion). For CL, it changed its left hind limb's kinematics according to the obstacle's height and position relative to the left foot. In SL, the monkey used a "defensive posture", which included a rapid lowering of the right foot and forelimb movements, to stabilize the perturbed posture and thereby prevent falling. Then, with powerful extensions of its lower limb joints, the monkey raised its center-of-mass to the appropriate level for continuation of normal bipedal walking. The results show that M. Fuscata recruited both anticipatory and reactive neural mechanisms to accommodate to the obstacle.

Animals↗

PubMed2001

[Improvement of 99mTc-pyrophosphate scintigraphy in detection of acute myocardial infarction: combined with 99mTc-tetrofosmin].

BACKGROUND: 201Tl and 99mTc-pyrophosphate (PYP) dual scintigraphy is daily used in the detection of acute myocardial infarction (AMI). However, 201Tl is not available on emergent situation. We proposed a new method for detection of AMI combined 99mTc-PYP with 99mTc-tetrofosmin (TF). METHODS: 99mTc-PYP (740 MBq) was administered to 25 patients with AMI, and 3.5 hours later, planar imaging (PYP planar) and SPECT were performed (PYP-SPECT). Immediately after cessation of PYP-SPECT, 99mTc-TF (370-740 MBq) was injected and 5 minutes later SPECT was performed in the same position (TF-SPECT). PYP-SPECT and TF-SPECT were reconstructed in the same geometric status to permit superimpose of PYP-SPECT and TF-SPECT images. Two experts and 2 beginners of nuclear medicine physician interpreted the images in three ways; PYP planar image only, PYP-SPECT, and PYP-SPECT with TF-SPECT. RESULTS: PYP-SPECT combined with TF-SPECT shows 100% detectability of the AMI lesions, which is significantly higher than other two methods in both experts and beginners. CONCLUSION: PYP-SPECT combined with TF-SPECT is a powerful method for detection of AMI.

Aged↗

PubMed2001

[Quantitative evaluation of esophageal scintigraphy in systemic sclerosis].

BACKGROUND: Esophageal involvement by systemic sclerosis (SSc) is frequent. The purpose of this study was to evaluate esophageal motility disorders quantitatively. METHODS: We investigate esophageal scintigraphy in 22 patients with SSc. Esophageal scintigraphy was obtained with swallowing physiological saline in supine position, and swallowing soup in supine and sitting positions. Data was acquired with 0.5 sec per frame for 192 frames in the anterior view. We employed a condensed image as a visual evaluation, half-life and retention rate as a quantitative evaluation, which were obtained from time-activity curves generated from regions of interest on the whole esophagus. The half-life and retention rate were compared with classification of Barnett, stages of SSc, and modified Rodnan total skin score (TSS). RESULTS: No significant differences were seen in classification of Barnett and the stages of SSc. No significant difference was seen between swallowing water and soup in the supine position. The retention rate was significantly prolonged in the supine position than in the sitting position. The retention rate of soup study in the sitting position correlated with TSS (r = 0.61). CONCLUSION: Esophageal scintigraphy in the sitting position is useful in evaluation of esophageal motility in SSc.

Adult↗

PubMed2001

[A case of combined squamous cell carcinoma and aspergilloma arising in a cyst wall].

A 76-year-old man in whom interstitial pneumonia and diabetes mellitus had been diagnosed complained of bloody sputum in August, 1998. Chest radiography disclosed irregular shadows in the left lower lung field. Chest computed tomography (CT) scans revealed a cyst and a small nodular lesion in the left S6 segment. Although primary lung cancer was suspected, we did not detect any malignant cells in the transbronchial lung biopsy specimen. CT scans in January 2000 showed a ball-like shadow in the thick-walled cyst in the left S6 segment. Cytologic examination of the sputum and the bronchial lavage fluid from the left B6 revealed squamous cell carcinoma. Left lower lobectomy and mediastinal lymph node dissection were performed. Pathological examination revealed that moderately differentiated squamous cell carcinoma had extensively invaded the wall of the cyst in the left S6 and S10 segments, and was accompanied with aspergilloma. Abnormal thickening of a cyst wall may in some cases suggest the presence of lung cancer.

Aged↗

PubMed2001

[A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), showing temporary improvement during the treatment with eicosapentaenoic acid ethyl ester].

We report a 67-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), successfully treated with eicosapentaenoic acid ethyl ester (EPA-E) for about eight months. He showed bilateral auditory disturbance and slowly progressive gait ataxia at age 50 during treatment of diabetes mellitus (DM) with subcutaneous injection of insulin since age 29. At age 58 he manifested an acute hemiparesis of right extremities for one week with no abnormal findings on neuroradiological examinations. A permanent pacemaker was implanted at age 61 to treat frequent syncopal attacks due to complete atrioventricular block. On admission to our hospital, neurological examinations revealed dementia, auditory disturbance, severe cerebellar ataxia and mild atrophy of proximal muscles with systemic hyporeflexia. Based on a point mutation in position 3243 of mitochondrial DNA, he was diagnosed as having MELAS with severe DM, auditory disturbance and cardiac conduction block. After initiation of treatment with EPA-E at a dose of 2,700 mg/day he showed temporarily an improvement in auditory disturbance, blood glucose control and cerebellar ataxia. In objective evaluations for cerebellar ataxia, we could find significant decreases in times for 20 m walking and heel-knee patting in the ninth month, and in time for tracing of a whirl from the third to the ninth month, compared with those before treatment of EPA-E (p < 0.0001). Because EPA-E is taken into mitochondrial membranes and activates electron transmission enzyme complexes, it might be a candidate for therapy of mitochondrial encephalomyopathy, including MELAS.

Aged↗

PubMed2000

Change in receptor-binding specificity of recent human influenza A viruses (H3N2): a single amino acid change in hemagglutinin altered its recognition of sialyloligosaccharides.

Human H3N2 influenza A viruses were known to preferentially bind to sialic acid (SA) in alpha2,6Gal linkage on red blood cells (RBC). However, H3N2 viruses isolated in MDCK cells after 1992 did not agglutinate chicken RBC (CRBC). Experiments with point-mutated hemagglutinin (HA) of A/Aichi/51/92, one of these viruses, revealed that an amino acid change from Glu to Asp at position 190 (E190D) was responsible for the loss of ability to bind to CRBC. A/Aichi/51/92 did not agglutinate CRBC treated with alpha2, 3-sialidase, suggesting that SAalpha2,3Gal on CRBC might not inhibit the binding of the virus to SAalpha2,6Gal on CRBC. However, the virus agglutinated derivatized CRBC resialylated with SAalpha2, 6Galbeta1,4GlcNAc. These findings suggested that the E190D change might have rendered the HA able to distinguish sialyloligosaccharides on the derivatized CRBC containing the SAalpha2,6Galbeta1,4GlcNAc sequence from those on the native CRBC.

Amino Acid Substitution↗

PubMed2000

Ordered networks of rat hippocampal neurons attached to silicon oxide surfaces.

The control of neuronal cell position and outgrowth is of fundamental interest in the development of applications ranging from cellular biosensors to tissue engineering. We have produced rectangular networks of functional rat hippocampal neurons on silicon oxide surfaces. Attachment and network formation of neurons was guided by a geometrical grid pattern of the adhesion peptide PA22-2 which matches in sequence a part of the A-chain of laminin. PA22-2 was applied by contact printing onto the functionalised silicon oxide surface and was immobilised by hetero-bifunctional cross-linking with sulfo-GMBS. Geometric pattern matching was achieved by microcontact printing using a polydimethylsiloxane (PDMS) stamp. In this way the produced grid pattern ranged from 3 to 20 microm in line width and from 50 to 100 microm in line distances. As shown by atomic force microscopy (AFM), line widths and line distances of the peptide pattern differ less than 0.5 microm from the used PDMS stamp. The height of the layer of immobilised PA22-2 was approximately 3.5 nm implying the layer to be monomolecular. Immobilised PA22-2 was capable of binding anti-PA22-2 antibodies indicating that the function of the peptide was not compromised by immobilisation. Rat hippocampal neurons, cultured at low density in serum-free medium, were applied to the growth matrix of PA22-2-coated substrates and, within 1-3 h of culture, formed a network-like pattern that more or less matched the printed grid. Reliability and reproducibility of neuronal network formation depended on the geometry, line width and node diameter of the grid pattern. The immobilised neurons showed resting membrane potentials comparable with controls and, already after 1 day of culture, were capable of eliciting action potentials. The suitability of the immobilised neurons for the study of man-made neural networks and for multi-site recordings from a functional neuronal network is discussed.

Animals↗

PubMed2000

Determination of functional regions of p125, a novel mammalian Sec23p-interacting protein.

The Sec23p-Sec24p complex is a component of coat protein II-coated vesicles involved in protein export from the endoplasmic reticulum. We previously identified a novel Sec23p-interacting protein, p125, which consists of 1000 amino acids and comprises a proline-rich region and a phospholipase A(1) homology region. p125, when ectopically expressed in cultured cells, localizes to endoplasmic reticulum-Golgi intermediate regions. In the present study we showed that expressed p125 principally colocalizes with p115 and GM130, both of which are involved in vesicle tethering to Golgi membranes. Next, we determined the functional regions of p125 by expressing a p125 series with deletions. The results showed that the proline-rich region (residues 135-259) is responsible for the binding to Sec23p. For the correct localization of p125, a region (residues 135-1000) comprising both the proline-rich and phospholipase A(1) homology regions was required.

Animals↗

PubMed2000

Clinical and Experimental Observation of Glistening in Acrylic Intraocular Lenses.

Purpose: To study whether the glistening on implanted acrylic intraocular lenses increases or not.Method: 1. Prospective study: We studied the glistening on 49 implanted acrylic intraocular lenses, particularly the time of appearance and increase after glistening appeared. 2. Experiment: We kept an intraocular lens immersed in saline solution at 50 degrees centigrade for 2 hours and then moved this lens into saline solution at 35 degrees centigrade, and observed this lens during immersion.Results: 1. Prospective study: Glistening was present in 28 eyes (57%), and appeared from 2 to 16 months postoperatively. A few months after appearance it become stable and did not increase further. 2. Experiment: On the 10th day after observation, we could see glistening on the lenses. The points of glistening were 10 µm or less in size, and did not change during 60 days of observation.Conclusion: The glistening in acrylic intraocular lenses seemed to become stable a few months after appearance. This our experimental method is useful, because it gives us glistening similar to clinical cases in a short time.

Journal Article↗

PubMed2000

Preparation of diynes via selective bisalkynylation of zirconacycles

Reaction of alkynyl halides with in situ prepared zirconacyclopentanes, -pentenes, and -pentadienes in the presence of CuCl under mild reaction conditions afforded alkynes or diynes. Control of the reaction conditions selectively afforded monoalkynylation products of zirconacycles. Reaction of zirconacycles with 2 equiv of alkynyl halides resulted in the formation of diynes. Selective monoalkynylation of zirconacycle with an alkynyl halide, followed by reaction with a different alkynyl halide, afforded unsymmetrical diynes. Bisalkynylation product of zirconacyclopentadiene was gradually converted into a tricyclic compound.

Journal Article↗

PubMed2000

Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines.

Lineage-specific transcription factors play crucial roles in the development of hematopoietic cells. In a previous study, it was demonstrated that Ras activation was involved in thrombopoietin-induced megakaryocytic differentiation. In this study, constitutive Ras activation by H-ras(G12V) evoked megakaryocytic maturation of erythroleukemia cell lines F-36P and K562, but not of myeloid cell line 32D cl3 that lacks GATA-1. However, the introduction of GATA-1 led to reprogramming of 32D cl3 toward erythrocytic/megakaryocytic lineage and enabled it to undergo megakaryocytic differentiation in response to H-ras(G12V). In contrast, the overexpression of PU.1 and c-Myb changed the phenotype of K562 from erythroid to myeloid/monocytic lineage and rendered K562 to differentiate into granulocytes and macrophages in response to H-ras(G12V), respectively. In GATA-1-transfected 32D cl3, the endogenous expression of PU.1 and c-Myb was easily detectable, but their activities were reduced severely. Endogenous GATA-1 activities were markedly suppressed in PU.1-transfected and c-myb-transfected K562. As for the mechanisms of these reciprocal inhibitions, GATA-1 and PU.1 were found to associate through their DNA-binding domains and to inhibit the respective DNA-binding activities of each other. In addition, c-Myb bound to GATA-1 and inhibited its DNA-binding activities. Mutant GATA-1 and PU.1 that retained their own transcriptional activities but could not inhibit the reciprocal partner were less effective in changing the lineage phenotype of 32D cl3 and K562. These results suggested that GATA-1 activities may be crucial for Ras-mediated megakaryocytic differentiation and that its activities may be regulated by the direct interaction with other lineage-specific transcription factors such as PU.1 and c-Myb.

Animals↗

PubMed2000

Target volume definition for upper abdominal irradiation using CT scans obtained during inhale and exhale phases.

PURPOSE: To evaluate the clinical utility of a treatment-planning technique involving the use of CT images obtained during both the static exhalation phase and static inhalation phase (two-phase planning). METHODS AND MATERIALS: Ten patients with pancreatic or liver tumors underwent CT scanning under static exhale and inhale conditions, after a period of mild ventilation. By setting image positions differently, we were able to treat the two-phase images as one dataset. Each gross tumor volume (GTV) was contoured separately and the mixed GTV was used for the two-phase treatment planning. Treatment plans were constructed to compare the two-phase plans with the plans constructed using static exhalation images. The shift of the center of the GTV and kidneys and the minimum dose of GTV were then calculated. RESULTS: The shift of the GTV ranged from 2.6 to 27. 3 mm and that of the kidneys from 2.2 to 24 mm. In some patients whose treatment was planned using exhalation planning, the minimum dose of GTV at inhalation was less than 90% of the isocenter dose. CONCLUSION: Two-phase planning is a simple technique that can visualize tumor and organ movement simultaneously using CT. It further defines adequate field margins around the tumor and prevents unexpected radiation exposure to critical organs. Routine use of this technique for upper abdominal irradiation is recommended.

Abdominal Neoplasms↗

PubMed2000

Variation in response among individuals to antigenic sites on the HA protein of human influenza virus may be responsible for the emergence of drift strains in the human population.

Eight convalescent human sera obtained from patients aged 3 to 14 years old, who were infected with influenza A(H3N2) virus during the 1990/1991 influenza season, were characterized by a binding assay with chimeric hemagglutinin (HA) proteins between influenza virus A/Aichi/2/68 and A/Kamata/14/91(H3N2) strains. These sera did not recognize the HA protein of the A/Aichi/2/68 strain but recognized that of the A/Kamata/14/91 strain. The binding assay revealed that these sera recognized only the HA1 domain of A/Kamata/14/91 HA protein. A further assay of the binding of these sera to the chimeric proteins of the HA1 domain revealed that three sera (A-1, A-2, and A-3) from very young patients bound only to region 150-170 (site B1) and one serum (Y-1) bound to regions 96-150 (site A) and 96-170 (sites A and B1). These four sera showed reduced hemagglutination inhibition (HI) activity with the 203v2 strain, a monoclonal variant of the A/Kamata/14/91 strain with two amino acid changes in the HA protein at antigenic sites A and B1. The other four sera (Y-2, G-1, G-2, and A-4) bound to regions 1-96 (site C/E), 96-150 (site A), 96-170 (sites A and B1), and 170-200 (site B2), two of which further bound to region 240-306 (site C); these sera were all fully reactive with the 203v2 strain. All eight sera showed reduced HI reactivity to a drift strain A/Aichi/4/93. Amino acid changes of the A/Aichi/4/93 strain from the A/Kamata/14/91 strain were located at antigenic sites A, B1, B2, and C. We propose a possible model for the emergence of a drift strain A/Aichi/4/93 from an A/Kamata/14/91-like strain by sequential changes during reinfections of individuals starting from A-1-like, next to Y-1-like, and then to Y-2-like populations.

Adolescent↗

PubMed2000

Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody.

Reelin is a key mediator of ordered neuronal alignment in the brain. Here, we demonstrate that Reelin molecules assemble with each other to form a huge protein complex both in vitro and in vivo. The Reelin-Reelin interaction clearly is inhibited by the function-blocking anti-Reelin antibody, CR-50, at a concentration known to inhibit Reelin function. This assembly is mediated by electrostatic interaction of the CR-50 epitope region. Recombinant CR-50 epitope fragments spontaneously constitute a soluble, string-like homopolymer with a regularly repeated structure composed of more than 40 monomers. Mutated Reelin, which lacks the CR-50 epitope region, cannot form a homopolymer and fails to induce efficient tyrosine phosphorylation of Disabled 1 (Dab1), which should occur to transduce the Reelin signal. These data suggest that Reelin exerts its biological function by composing a large protein assembly driven by the CR-50 epitope region, proposing a novel model of the Reelin signaling in neurodevelopment.

Animals↗

PubMed2000

Combined tachykinin receptor antagonist: synthesis and stereochemical structure-activity relationships of novel morpholine analogues.

We report herein the synthesis and stereochemical structure-activity relationships of novel morpholine analogues 12 and 13 with regards to NK1, NK2 and NK3 tachykinin receptor binding affinity. An essential requirement for more potent binding affinities was controlled by absolute configuration. (S,R)-12 and (S,R)-13 exhibited high binding affinities for NK1, NK2 and NK3 receptors.

Animals↗

PubMed2000

Full oncogenic activities of v-Src are mediated by multiple signaling pathways. Ras as an essential mediator for cell survival.

Tyrosine kinase oncoproteins cause simultaneous activation of multiple intracellular signaling pathways. However, the precise mechanisms by which individual pathways induce oncogenesis are not well understood. We have investigated the roles of individual signaling pathways in v-Src-dependent cell growth and survival by inhibiting one particular pathway. v-Src induced constitutive activation of signal transducers and activators of transcription 3 (STAT3), phosphatidylinositol 3-kinase, and Ras in murine Ba/F3 cells and led to factor-independent proliferation. Dominant-negative mutants of STAT3 (STAT3D) and phosphatidylinositol 3-kinase (Deltap85) inhibited v-Src-dependent growth by approximately 60 and approximately 40%, respectively. Moreover, dominant-negative Ras (N17) induced severe apoptosis, which was accompanied by down-regulation of Bcl-2 and activation of caspase-3. Although cells overexpressing Bcl-2 or caspase-3 inhibitors remained viable even when N17 was expressed, the growth was reduced by approximately 85%. During N17- and STAT3D-induced growth suppression, expression of cyclin D2, cyclin D3, c-myc, and c-fos was suppressed by N17, whereas that of cyclin D2, cyclin E, and c-myc was suppressed by STAT3D. Thus, v-Src-activated Ras and STAT3 are involved in distinct but partly overlapping transcriptional regulation of cell cycle regulatory molecules. These results suggest that the full oncogenic activity of v-Src requires simultaneous activation of multiple signalings, in which Ras is particularly required for survival.

Animals↗