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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 469 records · Page 26Linked to original sources

A newly designed radioimmunoconjugate releasing a hippurate-like radiometal chelate for enhanced target/non-target radioactivity.

Target-to-non-target ratio of radioactivity can be enhanced by the injection of monoclonal antibodies (MoAbs) labeled with metallic radionuclides, if some modality to accelerate the urinary excretion of radioactivity accumulated in non-target tissues could be introduced. In this study, a radioimmunoconjugate chemically designed to release a hippurate-like radiometal chelate was synthesized and tested in vivo. A 67Ga chelate of succinyldeferoxamine (SDF) was conjugated with a MoAb against osteogenic sarcoma (OST7, IgG1) through an ester bond using a new metabolizable MESS linker, N-[I4-(maleimidoethoxy)succinyl]oxy]succinimide (67Ga-DFO-MESS-OST7). When injected into normal mice, 67Ga-DFO-MESS-OST7 exhibited faster clearance of radioactivity from circulation with less accumulation in the liver, kidney and spleen than those observed with 67Ga-DFO-EMCS-OST7, which was prepared under identical conditions to 67Ga-DFO-MESS-OST7 except for using a non-metabolizable linker holding no ester bond to release 67Ga-SDF. Size exclusion HPLC analysis of the liver homogenate obtained from mice 24 h after injection of 67Ga-DFO-MESS-OST7 indicated that all the radioactivity was eluted in the high molecular weight fraction with most of it being present as the 67Ga-DFO-MESS-OST7 fraction. Reverse-phase HPLC analysis of urine sample from the same mice showed a single radioactivity peak at the same retention time as that of 67Ga-SDF. In athymic mice bearing osteogenic sarcoma, 67Ga-DFO-MESS-OST7 exhibited higher tumor-to-blood and tumor-to-organ ratio of radioactivity when compared with 67Ga-DFO-EMCS-OST7. These results indicated that 67Ga-DFO-MESS-OST7 achieved enhanced target-to-non-target ratio of the radioactivity, due to preferential cleavage of the ester bond in non-target tissues, followed by rapid urinary excretion of the resulting chelate (probably as 57Ga-SDF). These results also suggest that the present design would become an applicable modality for enhancing the target-to-non-target ratio of radioactivity by MoAbs.

Animals↗

Characteristic bright signal of parotid pleomorphic adenomas on T2-weighted MR images with pathological correlation.

The purpose of this study was to correlate the MR features and histological findings of pleomorphic adenomas, which are the most common tumour of the parotid gland, and to distinguish them from other types of tumour in the parotid gland. The materials studied consisted of 20 pleomorphic adenomas, including 12 untreated and eight recurrent cases, 17 other benign parotid tumours, and 12 malignant tumours. T1- and T2-weighted images and Gd-DTPA enhanced T1-weighted images were obtained. Characteristic bright signals with a higher intensity than that of CSF were seen in all of the pleomorphic adenomas on T2-weighted images, and were found to represent myxoid areas histologically. Although the cystic spaces in some benign tumours produced bright signals, these areas were distinguished from myxoid areas due to nonenhancement with Gd-DTPA. No bright signals were seen in the malignant tumours. In conclusion, bright signals on T2-weighted images represent myxoid tissue and are useful findings for diagnosing pleomorphic adenomas.

Adenolymphoma↗

Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA).

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurologic disorder characterized by variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. By specifically searching published brain cDNA sequences for the presence of CAG repeats we identified unstable expansion of a CAG in a gene on chromosome 12 in all the 22 DRPLA patients examined. A good correlation between the size of the CAG repeat expansion and the ages of disease onset is found in this group. Patients with earlier onset tended to have a phenotype of progressive myoclonus epilepsy and larger expansions. We propose that the wide variety of clinical manifestations of DRPLA can now be explained by the variable unstable expansion of the CAG repeat.

Adolescent↗

Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene.

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to 14q22.1-q22.2. The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzyme's activity in mononuclear blood cells, confirms that the GTP cyclohydrolase I gene is a causative gene for HPD/DRD. This is the first report of a causative gene for the inherited dystonias.

Age of Onset↗

Construction and expression of chimeric antibodies by a simple replacement of heavy and light chain V genes into a single cassette vector.

A novel vector pMH-gpt, which is proved useful for cloning mouse immunoglobulin heavy and light chain V genes and for expressing mouse-human chimeric antibody, was constructed. The vector contains human genomic C gamma 1 and C kappa genes, cloning sites for immunoglobulin V region genes, murine Ig promoters, a human Ig heavy chain enhancer, and the selection marker gene Eco-gpt. Because VH and V kappa genes can be cloned into a single vector, a chimeric antibody gene is easily constructed by this simple insertion procedure. The usefulness of the vector was confirmed by construction of two mouse-human chimeric antibodies. Mouse monoclonal antibody (MAb) 196-14 recognizes the ovarian cancer-associated antigen (CA125), and MoAb 2-18 reacts with carcinoembryonic antigen (CEA). Mouse-human chimeric 196-14 and 2-18 antibodies were readily constructed and efficiently produced in a mouse myeloma cell line by utilizing the vector. Both chimeric antibodies retained binding activity to their respective antigens. In biodistribution and immunoscintigraphy studies, specificity of radiolabeled chimeric 196-14 antibody was identical to that of its murine counterpart and significant accumulation at the tumor site was observed. The pMH-gpt vector is useful for constructing and producing mouse-human chimeric antibodies.

Amino Acid Sequence↗

Incidental finding of herpes zoster infection by Tc-99m HMPAO.

Tc-99m HMPAO brain SPECT study incidentally demonstrated a large area of increased accumulation in the soft tissue of the face and fronto-parietal region of the head, corresponding to the distribution of the ophthalmic and maxillary branches of the trigeminal nerve, which had been infected by herpes zoster.

Aged↗

BE-23372M, a novel and specific inhibitor for epidermal growth factor receptor kinase.

The fungal metabolite BE-23372M is a structurally novel protein kinase inhibitor. Its IC50 for epidermal growth factor (EGF) receptor kinase was 0.03 microM. IC50 values of BE-23372M for other protein tyrosine kinases, erbB-2, p43v-abl, insulin receptor kinase, and p60c-src were 0.42, 1.0, 3.3, and 4.5 microM, respectively, and the IC50 for protein kinase C, a serine/threonine kinase, was 4.1 microM. Cdc2 kinase, casein kinases I and II and cAMP-dependent protein kinase were not inhibited by 20 microM BE-23372M. A kinetic study showed that BE-23372M was competitive with respect to the substrate peptide and to ATP. Autophosphorylation of solubilized EGF receptor kinase was clearly inhibited by 0.1 microM BE-23372M. Autophosphorylation of EGF receptor in A431 cells was also inhibited. These results show that BE-23372M is a potent and specific EGF receptor kinase inhibitor. It should be a valuable tool for EGF receptor kinase research.

Amino Acid Sequence↗

Soft-tissue tumors: diagnosis with Tc-99m (V) dimercaptosuccinic acid scintigraphy.

PURPOSE: To assess the potential of technetium-99m (V) dimercaptosuccinic acid (DMSA) scintigraphy for diagnosis of soft-tissue tumors. MATERIALS AND METHODS: Tc-99m (V) DMSA scintigraphy was performed in 76 patients with histologic proof of soft-tissue tumors. In 57 of these patients, gallium-67 citrate scintigraphy was performed within 2 weeks after Tc-99m (V) DMSA scintigraphy. RESULTS: Uptake of Tc-99m (V) DMSA was clearly detected in almost all sarcomas, metastatic carcinomas, highly recurrent benign tumors (ie, extra-abdominal desmoids and tenosynovial giant cell tumors), superficial and deep hemangiomas, and granulomatous soft-tissue lesions but was not found in other benign solid tumors of soft tissue. Uptake of Ga-67 citrate was clearly detected in all inflammatory lesions and metastatic carcinomas, eight of 14 sarcomas (57%), and two of 10 highly recurrent benign tumors (20%) but was not found in hemangiomas or benign soft-tissue tumors. CONCLUSION: Low-grade malignant and highly recurrent benign lesions, which often recur after surgery, were detected more accurately with Tc-99m (V) DMSA scintigraphy than with Ga-67 citrate scintigraphy.

Adolescent↗

Response of commissural and other upper cervical ventral horn neurons to vestibular stimuli in vertical planes.

1. To study their contribution to the vestibulocollic reflex, we have studied, in decerebrate paralyzed cats, the effect of sinusoidal vestibular stimulation in multiple vertical planes on the spontaneous activity of neurons in the C3 ventral horn. Antidromic microstimulation was used to identify 17/42 neurons as commissural; 10 of these were confirmed to have a projection to the contralateral ventral horn. 2. Dynamics of the responses of spontaneously firing neurons were studied with 0.05-1 Hz sinusoidal stimuli delivered near the plane of rotation that produced maximal modulation of neuron activity (response vector orientation). On the basis of their responses, we classified 38 neurons as receiving otolith, semicircular canal, or otolith + canal input. All three response types were found among commissure and nonantidromic neurons. 3. Two-thirds of neuron response vector orientations pointed contralaterally. They were either near the anterior or posterior canal planes or in the roll quadrant. In the case of neurons with input from canals, the latter indicates convergence from the vertical canals on the same side. There were almost no vectors in the pitch quadrants. The distribution of response vector orientations resembles that seen in the vestibular nuclei and pontomedullary reticular formation, suggesting that commissural neurons may not make a new contribution to spatial processing in the vertical vestibulocollic reflex. 4. It is presumed that commissural neurons are premotor. If so, some have the properties to be in the pathway between the contralateral utricle and neck motoneurons. More generally, their actions could modify the effectiveness of vestibulospinal and reticulospinal fibers that have similar spatial properties and make synapses with neck motoneurons.

4-Aminopyridine↗

Spatiotemporally differential inhibition of pyramidal cells in the cat motor cortex.

1. The spatiotemporal pattern of inhibition in the cat motor cortex was studied in in vitro slice preparations in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV). 2. After intracortical microstimulation (0.5-6 microA), fast and slow inhibitory postsynaptic potentials (IPSPs) were produced in layers II-VI pyramidal cells and selectively reduced with bicuculline methiodide and phaclofen, respectively. 3. Fast IPSPs were maximally produced by stimulation of the same layer where their cell bodies were located, and they decreased in amplitude as the more superficial layer was stimulated. In contrast, slow IPSPs were maximally produced by stimulation of layer II regardless of the location of the recorded pyramidal cell and decreased in amplitude as the deeper layer was stimulated. 4. The reduction of amplitude of fast IPSPs, in response to a vertical shift of the stimulation site toward more superficial layers, was always correlated with an increase in rise time and with a shift of the reversal potential to a more hyperpolarized level. 5. When the stimulation site was moved horizontally to the more lateral site, fast IPSPs increased in latency and decreased in amplitude gradually without appreciable changes in rise time. Fast IPSPs could be evoked from horizontally remote sites of up to 800-1,200 microns. 6. Inhibitory interneurons, which are responsible for evoking fast IPSPs, appear to be distributed through almost all layers to send horizontally spreading parallel axons making synaptic contacts at different electrotonic distances along apical dendrites of single pyramidal cells. 7. Horizontal spreads were much less in slow IPSPs (< 340-680 microns). The time-to-peak of slow IPSPs produced in layer V pyramidal cells (159.5 +/- 6.8 ms, mean +/- SD, n = 10) was significantly (P < 0.0001) longer than that in layers II and III pyramidal cells (128.5 +/- 7.5 ms, n = 7). Asymmetric reversal properties of slow IPSPs were seen, suggesting the spatial dispersion of synaptic inputs along apical dendrites of pyramidal cells. 8. In layer V pyramidal cells, the time-to-peak of slow IPSPs decreased with increasing membrane hyperpolarization, indicating that the later portion of slow IPSPs was more sensitive to the membrane-potential change than the early portion. This further indicates that the late portion of slow IPSPs is generated at synapses on the more proximal dendrite of pyramidal cells than the early portion, contrary to that expected from the Rall's model of passive dendrite under the condition of synchronous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Monosynaptic and disynaptic connections in the utriculo-ocular reflex arc of the cat.

1. Connections from the utricular (UT) nerve to motoneurons and interneurons in the ipsilateral abducens (AB) nucleus were studied in anesthetized and decerebrated cats. Bipolar electrodes were fixed on the left UT nerve under visual observation. The other branches of the vestibular nerve and the facial nerve were transected in the left inner ear. 2. Stimulation of the UT nerve evoked a small positive-negative (P/N) deflection and a negative (N1) potential in the vestibular nuclei, with mean latencies of 0.56 and 0.84 ms, respectively. In the AB nucleus a small P/N deflection with a mean latency of 0.72 ms was recorded, which was considered as a incoming volley of the UT nerve. 3. Excitatory postsynaptic potentials (EPSPs) were recorded from AB motoneurons with short latencies after UT nerve stimulation. They were classified into two types, M and D. M-type EPSPs, which followed repetitive high-frequency stimuli and were recorded from the majority of AB motoneurons, had latencies ranging from 0.9 to 1.2 ms. Double shocks to the UT nerve evoked EPSPs that had the same latency. It was suggested that the AB motoneurons had monosynaptic connections with the UT nerve. D-type EPSPs, which were recorded from most of the AB motoneurons, had slightly longer latencies ranging from 1.2 to 1.8 ms. They showed temporal facilitation when double shocks were provided to the UT nerve. They did not follow repetitive high-frequency stimuli (< or = 2.5-ms interval). It was suggested that D-type EPSPs were di-synaptically evoked via secondary vestibular neurons. Interneurons in the AB nucleus had the same characteristics as AB motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Abducens Nerve↗

Characterization of CA125 glycoprotein using 3 monoclonal antibodies with different specificities.

CA125 and CA130 in various tissues were characterized using the monoclonal antibodies OC125, 130-22, and 145-9. CA125 and CA130 were eluted in the same fraction in 130-22 affinity chromatography. A sandwich immunoradiometric assay using these antibodies in combination was established. When the solid phase of the assay was changed from OC125 to 145-9, the amount of 125I-OC125 that reacted with CA125 in the amnion increased more than that in other samples. On SDS-PAGE, CA125 and CA130 epitopes in the amnion migrated to different positions. These results indicate that CA125 and CA130 are located on different subunits of the same glycoprotein, and that their synthesis is regulated differently in various tissues.

Amnion↗

Effects of thyroid hormone on carbonic anhydrase I levels in human erythroid (YN-1) cells.

We recently have reported that patients with hyperthyroidism have red blood cell carbonic anhydrase I (CAI) levels that reflect the patient's integrated thyroid hormone level over the preceding few months. In the present study, the effect of T3 on CAI concentrations in the human erythroleukemic cell line, YN-1, was studied. The presence of high affinity (1.9 x 10(9) L/mol), low capacity (20.4 fmol/10(6) cells) T3 binding sites was demonstrated in YN-1 cell nuclei. T3 at a physiological free T3 concentration (0.54 nmol/L) significantly (32 +/- 7%, P < 0.01) decreased CAI concentrations in YN-1 cells before induction of differentiation. The effect of T3 on CAI levels was more obvious (42 +/- 7%, P < 0.01) in the presence of transforming growth factor-beta 1 (TGF-beta 1), which induces hemoglobin synthesis and differentiation in YN-1 cells. These results suggest that the YN-1 cell line may be used to study T3 action on human red blood cell CAI.

Carbonic Anhydrases↗

Marchantin A trimethyl ether: its molecular structure and tubocurarine-like skeletal muscle relaxation activity.

Marchantin A is a novel macrocyclic bis(bibenzyl)ether isolated from the liverwort Marchantia species. An X-ray study of its derivative, marchantin A trimethyl ether, revealed that the molecule possesses convex and concave surfaces, with a central hole on the concave surface. The centroid-centroid separations of opposing benzene rings are 8.80 and 4.55 A. A pharmacological study showed that the skeletal muscle relaxation activity is about 3.5 times less potent than that of d-tubocurarine. A comparison of the X-ray structure of marchantin A trimethyl ether and that of O,O',N-trimethyltubocurarine reported by Sobell et al. revealed that the molecules share almost the same macrocyclic bis(bibenzyl)ether skeleton structure, portions of which may therefore be crucial for the skeletal muscle relaxation activity.

Animals↗

Parotid and parapharyngeal tumours: tissue characterization with dynamic magnetic resonance imaging.

Prospective studies were performed to characterize parotid and parapharyngeal tumours using dynamic magnetic resonance (MR) imaging. Bolus injection of gadopentetate dimeglumine and a short SE sequence were used to evaluate 23 masses including seven pleomorphic adenomas, seven Warthin's tumours and nine malignant tumours. Contrast enhancement profiles helped to distinguish the different types of parotid and parapharyngeal tumours. Gradual increase in intensity during the first 260 s after the injection was characteristically found in pleomorphic adenomas and adenoid cystic carcinomas. Conversely, all Warthin's tumours showed a rapid increase during the first 20 s followed by a decrease in signal intensity. The other malignant tumours showed a rapid increase during the first 20 s followed by gradual decrease or increase at a slow rate. We suggests that the gradual increase in signal intensity of pleomorphic adenoma and adenoid cystic carcinoma may be due to their hypovascularity and an abundance of interstitial regions rich in connective tissue-type mucin. Dynamic MRI shows promise in tissue characterization of parotid and parapharyngeal tumours.

Adenolymphoma↗

Case report: uptake of pentavalent technetium-99m dimercaptosuccinic acid by pigmented villonodular synovitis: comparison with computed tomography, magnetic resonance imaging and gallium-67 scintigraphy.

The scintigraphic findings of a patient with pigmented villonodular synovitis are described and compared with the computed tomography and magnetic resonance imaging data. Intense uptake of pentavalent technetium-99m dimercaptosuccinic acid without gallium-67 citrate uptake indicates that pigmented villonodular synovitis has the features of a hyperplastic or neoplastic lesion rather than an inflammatory lesion from the point of view of nuclear medicine.

Adult↗

Effects of titanium nitride coatings on surface and corrosion characteristics of Ni-Ti alloy.

The structure of a titanium nitride film coated by arc ion plating on a Ni-50Ti shape memory alloy was characterized by X-ray photoelectron spectroscopy (XPS). The corrosion behavior of the titanium nitride-coated Ni-50Ti alloy was examined in 0.9% NaCl solution by potentiodynamic polarization measurements and a polarization resistance method. XPS spectra showed that the titanium nitride film consisted of three layers, a top layer of TiO2, a middle layer of TiNx (x > 1), and an inner layer of TiN. The passive current density for the titanium nitride-coated alloy was approximately two orders of magnitude lower than that of the polished alloy in the potential range from the free corrosion potential to +500 mV (vs. Ag/AgCl). Pitting corrosion associated with breakdown of the coated film occurred above this potential. The polarization resistance data also indicated that the corrosion rate of the titanium nitride-coated alloy at the free corrosion potential (+50-+100 mV) was more than one order of magnitude lower than that for the polished alloy.

Corrosion↗