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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 289 records · Page 16Linked to original sources

[Clinical evaluation of combination therapy with cefpirome and amikacin for infections associated with hematological disorders].

Cefpirome (CPR) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 100 subjects were evaluated, and the allover efficacy rate was 72.0%. Acute leukemia was found in the largest number of patient, 55, followed by 12 cases of malignant lymphoma and 6 cases of chronic myelogenous leukemia. By type of infection, patients having suspected sepsis were the largest in number, being 50, and the efficacy rate was 68.0%. The efficacy rates for sepsis and pneumonia were 57.1% (7 cases) and 61.1% (18 cases), respectively. The efficacy rates by neutrophil counts before administration of CPR and AMK and at 7 days after administration were both 71.9% in the group of less than 500/microliter, both 60.0% in the group of less than 100/microliter. The efficacy rate was 75.0% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 70.0% in the non-concomitant usage group. Concomitant treatment with CPR and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases and high.

Adolescent↗

In vivo comparison of PET and SPECT radiopharmaceuticals in detecting breast cancer.

UNLABELLED: Various radiopharmaceuticals for breast cancer detection have been used for scintimammography and PET. However, few comparative studies have described the uptake of radiopharmaceuticals as a method of detecting breast cancer. The aim of this study was to assess the radiopharmaceuticals for breast cancer imaging in experimental mice implanted with breast cancer cells. METHODS: Six radiopharmaceuticals were studied: three for PET [18F-fluorodeoxyglucose (FDG), L-18F-alpha-methyltyrosine (FMT) and 11C-methionine (C-Met)] and three for scintimammography [99mTc-tetrofosmin (TF), 99mTc-sestamibi (MIBI) and 201Tl-chloride (Tl)]. Biodistributions of six different tracers in mice implanted with MCF-7 breast cancer cells were studied 1 and 3 hr after injection. RESULTS: Tumor uptake 1 hr after injection was FMT = C-Met > FDG = TF > MIBI = Tl. Thallium-201-chloride showed the highest tumor-to-blood ratio (T/B) among all radiopharmaceuticals because of its fast clearance from circulation. The T/B of the six radionuclides used in this study ranged from 1.26 for C-Met to 12.83 for Tl. Tumor-to-muscle ratio (T/M) revealed FMT = C-Met > FDG > MIBI > TF = Tl. The T/M ranged from 0.20 for TF to 2.29 for FMT. Tumor-to-lung ratio (T/L) varied from 0.45 for TF to 2.41 for FMT. FMT revealed the highest T/L of all six radiopharmaceuticals. CONCLUSION: Among radiopharmaceuticals for PET, FMT seemed to be suitable in detecting MCF-7 tumor; whereas for scintimammography, MIBI, TF and Tl appeared to have almost the same detectability of MCF-7 tumor. The results of this study strongly suggest that FMT may have a potential in breast cancer imaging.

Animals↗

Noninvasive measurement of renal function with 99mTc-MAG3 gamma-camera renography based on the one-compartment model.

OBJECTIVE: The aim of this study was to develop a method for measuring renal function with 99mTc-MAG3 gamma-camera renography without blood or urine sampling and evaluate its feasibility. PATIENTS, MATERIAL AND METHODS: Twelve patients with nephrological disorders underwent 99mTc-MAG3 renography and para-aminohippurate clearance measurement. Plasma clearance of 99mTc-MAG3 (ClMAG) was calculated through early renal uptake of 99mTc-MAG3 after appropriate correction of parameters (background, measured attenuation coefficient of 99mTc, and the actual depth of kidneys measured with computed tomography), and on one-compartment assumption of the kinetics of 99mTc-MAG3. We compared the resultant ClMAG with standard effective renal plasma flow (ERPF), using the para-aminohippurate clearance method and with simulated ClMAG derived from the two-compartment model. RESULTS: ClMAG calculated by the one-compartment model (283+/-131 ml/min, mean +/- SD) correlated with ERPF (r = 0.94, p <0.001), and was similar to the simulated ClMAG estimated from the two-compartment model in all patients (283+/-139 ml/min). CONCLUSION: This alternative method, which employs theoretical modeling of the pharmacokinetics of 99mTc-MAG3, may provide easy, noninvasive measurement of individual renal function without blood sampling or in vitro equipment. Further studies should be warranted.

Computer Simulation↗

[Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of thyroid, breast and lung/mediastinum tumors--a report of multicenter phase III clinical trials].

Phase III clinical study in 136 patients diagnosed or strongly suspected of thyroid, lung/mediastinum or breast cancer was performed to determine clinical utility of 99mTc-MIBI in the localization of tumors, and the results in 135 were evaluated. Except taste peculiar in 43 patients and nausea in one, no adverse events were reported. Seven abnormal changes in vital signs and 27 in clinical laboratories were noted, which were all judged as having no or unlikely relationship to the agent. Out of 177 malignant lesions, 156 (88%) were detected with 99mTc-MIBI regardless of their histology or location. Of 6 benign tumors, 3 were detected. Fifteen sites of false positive in 11 malignant tumor patients and 5 sites in 6 patients with non-tumor disease were observed. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of tumors. Especially, the fact that 99mTc-MIBI detected remote metastatic lesions with high sensitivity is a great advantage over the other conventional imaging modalities.

Adult↗

Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth.

We previously reported a new type of signal-transducing adaptor molecule, STAM, which was shown to be involved in cytokine-mediated intracellular signal transduction. In this study, we molecularly cloned a 110-kDa phosphotyrosine protein inducible by stimulation with interleukin 2 (IL-2). The 110-kDa molecule was found to be a human counterpart of mouse Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) and to be associated with STAM. Tyrosine phosphorylation of Hrs is induced rapidly after stimulation with IL-2 and granulocyte-macrophage colony-stimulating factor as well as hepatocyte growth factor. The mutual association sites of Hrs and STAM include highly conserved coiled-coil sequences, suggesting that their association is mediated by the coiled-coil structures. Exogenous introduction of the wild-type Hrs significantly suppressed DNA synthesis upon stimulation with IL-2 and granulocyte-macrophage colony-stimulating factor, while the Hrs mutant deleted of the STAM-binding site lost such suppressive ability. These results suggest that Hrs counteracts the STAM function which is critical for cell growth signaling mediated by the cytokines.

Adaptor Proteins, Signal Transducing↗

Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to the nigrostriatal system.

We report the toxic effects of 3,4-dimethoxyphenylethylamine (DMPEA), and tetrahydropapaverine (THP) on the rat nigrostriatal system; THP is a tetrahydroisoquinoline compound which may be derived from DMPEA by conjugation of DMPEA and its oxidative metabolite, dimethoxyphenylacetaldehyde; both are potent inhibitors of mitochondrial complex I. These compounds were introduced to the unilateral caudate-putamen of male Sprague-Dawley rats over 7 days using a 200-microl mini-osmotic pump. Striatal dopamine on the injected side showed a significant decrease to 86% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA, and to 73% of the non-injected side after 7.90 micromol/7 days of THP infusion; as the non-injected side dopamine also reduced in the THP-injected rats, dopamine on the injected side was 55% of the saline control. Tyrosine hydroxylase (TH)-positive nigral neurons were decreased to 76% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA and to 77% after 7.90 micromol/7 days of THP infusion. Dimethoxyphenyl-tetrahydroisoquinoline compounds appear to be potent nigral neurotoxins.

3,4-Dihydroxyphenylacetic Acid↗

Extracellular sodium concentration has diverse effects on the hypoxia-induced increase in intracellular Ca2+ in rat hippocampal slices.

The intracellular free Ca2+ concentration ([Ca2+]i) in the CA1 pyramidal cell layer was measured using fura-2-loaded hippocampal slices prepared from adult rats. Hypoxia (oxygen-glucose deprivation) elicited a gradual increase in [Ca2+]i in normal Krebs solution. With a high extracellular sodium concentration ([Na+]o), the hypoxia-induced response was attenuated, its onset-latency was longer and the time constant of its decay phase was shorter than in controls. In contrast, hypoxia in low [Na+]o elicited a significantly enhanced response with a short onset-latency and delayed decay phase. This exaggerated response to hypoxia in low [Na+]o was reversed by pre-incubation of the slice in low [Na+]o prior to the hypoxic insult. Some possible mechanisms and the functional significance of the observed effects of [Na+]o on the hypoxia-induced increase in [Ca2+]i are discussed, with particular emphasis on the putative participation of the glutamate transporter and the sodium-calcium exchanger in hypoxia-induced neuronal injury.

Animals↗

Separation of Bombyxin from a neuropeptide of Bombyx mori showing Summer-morph-producing Hormone (SMPH) activity in the Asian Comma Butterfly, Polygonia c-aureum L.

A neuropeptide from brain-suboesophageal ganglion (Br-SG) complexes of the silkmoth, Bombyx mori, shows summer-morph-producing hormone (SMPH) activity in the Asian comma butterfly, P. c-aureum. The SMPH-active peptide was extracted and demonstrated to be almost the same molecular size as bombyxin (4-5kD), a nueropeptide which shows prothoracicotropic hormone (PTTH) activity when assayed in vitro with prothoracic glands (PGs) of 4th-instar B. mori larvae in vitro. A Sephadex G-50 fraction of 3-8kD molecules prepared from Br-SG complexes of B. mori adults was applied to CM-, SP-, DEAE- or QAE- Toyoperal columns at pH 5.6 (or pH 6.9). The SMPH-activity could be separated from the PTTH-activity (or bombyxin) by subjecting a SMPH- and PTTH-active preparation of B. mori to anion-exchange chromatography at pH 6.9. By reversed-phase HPLC following an anion-exchange chromatography, SMPH-activity was recovered in two fractions of 40-45% acetonitril. Results demonstrate that the B. mori peptide showing the SMPH-activity in P. c-aureum is a different molecule than bombyxin.

Journal Article↗

Gefarnate stimulates secretion of mucin-like glycoproteins by corneal epithelium in vitro and protects corneal epithelium from desiccation in vivo.

The effect of drugs for gastritis and gastric ulcer (ecabet sodium, gefarnate, teprenone, and troxipide) on the secretion of mucin-like glycoproteins from rat cornea were investigated in vitro and on a short-term, rabbit dry eye model in vivo. For the studies in vitro, cultured rat cornea sections (3 mm diameter) were incubated with radiolabeled sodium sulfate, rinsed, and then incubated for 30 min in the presence of one of the drugs. The culture media were reacted with Dolichos biflorus agglutinate (DBA)-lectin, and the radioactivity of DBA-bound mucin-like glycoproteins was measured. A cytotoxicity assay confirmed that mucin-like glycoproteins had not leaked from damaged cells. For studies in vivo, eye drop vehicle or drops containing gefarnate were instilled in the eyes of nine anesthetized rabbits, and then the eyes were kept open with specula for two hours. These rabbits and two control rabbits not subjected to ocular drying were killed, and their eyes were enucleated and stained with methylene blue. Corneal epithelial damage from desiccation was evaluated based on the extent of methylene blue staining. Among the four kinds of drugs for gastritis and gastric ulcers, only gefarnate significantly increased the mucin-like glycoprotein secretion from cultured rat corneas in vitro; this stimulatory effect of gefarnate was dose-dependent. In vivo, the instillation of gefarnate reduced corneal epithelial damage from desiccation in a dose-dependent fashion. These results suggest that gefarnate reduces desiccation of corneal epithelium, perhaps by stimulating secretion of mucin-like glycoproteins from corneal epithelium.

Animals↗

A PCR survey of hox genes in the sea star, Asterina minor.

The sea star, Asterina minor, was surveyed for Hox genes using the method of PCR and subsequent sequence determination. Seven different Hox-type homeobox fragments and homeobox fragments of two other types, the Gbx-type and the Xlox-type, were identified. The results of comparative analysis with known homeobox sequences suggest that the sea star has only one Hox gene cluster including two genes of the anterior group, four genes of the medial group, and one gene of the posterior group. The existence of a gene of the cognate group 1 has not been known in echinoderm species. Each of the other fragments indicated a definite relationship with one of sea urchin homeoboxes. The hypothetical cluster in the sea star is consistent with the results published for another class of echinoderm, sea urchins, in the putative number of cluster. The present result provides strong evidence that a single Hox cluster is common to echinoderms and its structure in the anterior region is more similar to other deuterostomes than previously thought.

Amino Acid Sequence↗

Isolation of radiosensitive and radioresistant mutants from a medulloblastoma cell line.

Two mutant clones, one radiosensitive (OS-3) and one resistant (OR-5), were isolated from ONS-76 after screening 2400 clones by the replica micro-well technique. These two clones exhibited significantly different radiosensitivity, with D37 values of 4.7Gy in OR-5 and 1.7Gy in OS-3. After gamma irradiation (8Gy), OR-5 exhibited greater G2 arrest than sensitive clone OS-3. Administration of 5mM of caffeine resulted in greater cell killing in OR-5 than in OS-3, with an almost complete release of G2 block. These observations support the notion that the G2 block contributes to the repair process of DNA damage after irradiation. The present results suggest that clones with a large postirradiation G2 block may show a greater reduction in radiosensitivity if the G2 block is released artificially. The study of the mutant clones described herein may provide important clues to the mechanism by which glioma cells acquire radioresistance.

Caffeine↗

Ventilation/perfusion ratios and simultaneous dual-radionuclide single-photon emission tomography with krypton-81m and technetium-99m macroaggregated albumin.

To date, there has been neither a good method to clarify the three-dimensional distribution of pulmonary ventilation/perfusion (V. A/Q.) ratios, nor a convenient way to assess V.A/Q. inequality. The purpose of this study was to develop a functional image of pulmonary V.A/Q. ratios based on data acquired with simultaneous dual-radionuclide single-photon emission tomography (SPET) and to assess V.A/Q. unevenness through the V.A/Q. histogram in patients with various pulmonary diseases. Dual-radionuclide SPET was performed with technetium-99m macroaggregated albumin (MAA) and krypton-81m, with the patient in the supine position. After correction for linear cross-talk, the total acquisition counts of both radionuclides were equalized. The V.A/Q. ratio, which was calculated in each pixel by dividing the 81mKr count by the 99mTc-MAA count, was expressed as a V.A/Q. image. A histogram of the pixel number plotted against the V.A/Q. ratios was then produced and its centre of weight (CW) and standard deviation (SD) determined. Ten healthy volunteers and 46 patients [seven with pulmonary vascular disease (PVD), nine with pulmonary emphysema (PE), 18 with bronchogenic carcinoma and 12 with miscellaneous diseases] participated in this study. In normal volunteers, V.A/Q. ratios were generally even, but were slightly lower in dorsal regions. Patients with PVD had lobar and/or segmental areas with a high V.A/Q. ratio. Low V.A/Q. areas extended widely in patients with PE. Bronchogenic carcinoma exceeding 3 cm in diameter was detected as a very low V. A/Q. area. The SD of V.A/Q. ratios had a significant positive correlation both with A-aDO2 (r=0.64, P<0.001) and with cigarette smoking history (r=0.72, P<0.001). It is concluded that the V.A/Q. ratio image produced with simultaneous dual-radionuclide SPET using 99mTc-MAA and 81mKr is a unique and simple method for demonstrating the three-dimensional distribution of V.A/Q. ratios. The unevenness of V.A/Q. distribution can be assessed through the SD of the V.A/Q. histogram.

Adult↗

Machado-Joseph disease gene products carrying different carboxyl termini.

Three cDNA clones for the Machado-Joseph disease gene (MJD1) were isolated, two of which have a new exon sequence and a distinct 3' terminal nucleotide sequence resulting in a new carboxyl terminal domain in the translated product. The nucleotide sequence of the other one is similar to the previously published one except for five polymorphisms, one of which is a single nucleotide substitution resulting in a change from the stop codon (TAA; allele A) to a tyrosine residue (TAC; allele C). Genetic analysis results suggest that Japanese MJD mutations are associated with allele A.

Amino Acid Sequence↗

The use of a multitracer technique for the studies of the uptake and retention of trace elements in rats.

The uptake by, and distribution and retention of radioactive isotopes in various organs of Wistar rats were examined using the multitracer technique. A hydrocholoric acid solution (pH 3) of a carrier-free radioactive multitracer was prepared from gold foil irradiated with a 14N beam of 135 MeV nucleon. The solution was administered orally to 12 7-week-old male rats. Urine and faeces were collected and each group of three rats was killed at 1, 2, 3 or 6 days after administration. The percentage of administered dose of the 17 elements, Mn, Co, Zn, As, Rb, Sr, Y, Eu, Gd, Er, Tm, Yb, Lu, W, Re, Ir and Pt in the organs blood and excreta were determined using gamma-ray spectrometry. Each element revealed its characteristic distribution among the different organs, including the blood. These results are discussed and compared with those of single-tracer experiments, and the advantages of the multitracer technique are presented.

Administration, Oral↗

Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand.

We prepared [11C]KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine, refs 10, 13) as well as its 11C-ethyl and 11C-methyl derivatives ([11C]EPDX and [11C]MPDX), and examined the potential of the three compounds as PET ligands for CNS adenosine A1 receptors. The three compounds had high affinity for the A1 receptors in vitro in the following order; [11C]EPDX > [11C]KF15372 > [11C]MPDX. In mice, the highest initial brain uptake was found in [11C]MPDX followed by [11C]EPDX and [11C]KF15372, but the level of [11C]MPDX decreased faster than those of the other two compounds. The uptake of each compound was decreased by carrier KF15372, but not by an A2A antagonist, indicating the selective affinity for the A1 receptors. Autoradiography with [11C]MPDX ex vivo demonstrated decreased A1 receptor binding in the superior colliculus of rats deprived of retino-collicular fibers by contralateral eye enucleation. These results show that three compounds have potential as PET ligands for CNS adenosine A1 receptors.

Animals↗

Preparation of yttrium-90-labeled human macroaggregated albumin for regional radiotherapy.

Human macroaggregated albumin (MAA), which is currently labeled with technetium-99m (99mTc) and 99mTc-MAA, is used clinically as a pulmonary perfusion agent and was directly labeled with yttrium-90 (90Y)-acetate. This study evaluated whether 90Y-MAA could be potential radiotherapeutic agent for regional radiotherapy against malignant tumors. MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 90Y-acetate and purified in order to get rid of unstable binding of 90Y by electrophoresis. The radiochemical purity of 90Y-MAA in normal human serum was estimated by an agarose electrophoresis method and was more than 94% over 168 h in vitro. Following the intratumoral administration of 90Y-MAA, the time course of tumor radioactivity and the biodistribution in nude mice bearing human neuroblastoma were investigated up to 168 h. More than 93% of the radioactivity of the injected dose was found on the subcutaneous tumor over 168 h. The bone radioactivity was shown as 0.06 +/- 0.03% injection dose/gram tissue (% ID/g) (n = 5) at 24 h, 0.73 +/- 0.20% ID/g at 72 h, 0.92 +/- 0.16% ID/g at 120 h, and 2.51 +/- 0.59% ID/g at 168 h. A slight increase in radioactivity was noted in the liver, kidneys, and spleen over the 168-h periods. In conclusion, 90Y-MAA may be a potential agent for regional radiotherapy (brachytherapy) because of the sufficient persistence in the tumor following an intratumoral administration.

Albumins↗

STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction.

We previously identified a putative signal transducing adaptor molecule, named STAM, that contains an Src homology 3 (SH3) domain and immunoreceptor tyrosine-based activation motif (ITAM). In this report, we demonstrate the functional significance of STAM in cytokine-mediated signal transduction. STAM is associated with Jak3 and Jak2 tyrosine kinases via its ITAM region and phosphorylated by Jak3 and Jak2 upon stimulation with IL-2 and GM-CSF, respectively. An SH3 deletion mutant of STAM confers a dominant-negative effect on DNA synthesis mediated by IL-2 and GM-CSF. Furthermore, the wild-type STAM, but not STAM mutants deleted of SH3 and ITAM, significantly enhances c-myc induction mediated by IL-2 and GM-CSF. These results strongly implicate STAM in the signaling pathways for cell growth and c-myc induction immediately downstream of the Jaks associated with the cytokine receptors.

Adaptor Proteins, Signal Transducing↗