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T Nagata

Publications and source records attributed to T Nagata.

At least 721 records · Page 40Linked to original sources

Three-dimensional molecular field analyses of octopaminergic agonists and antagonists for the locust neuronal octopamine receptor class 3.

The quantitative structure-activity relationship (QSAR) of a set of 70 octopaminergic agonists and 20 antagonists against octopamine receptor class 3 (OAR3) in locust nervous tissue was analyzed by molecular field analysis (MFA). MFA of these compounds evaluated effectively the energy between a probe and a molecular model at a series of points defined by a rectangular grid. Contour surfaces for the molecular fields are presented. These results provide useful information in the characterization and differentiation of octopaminergic receptor types and subtypes.

Animals↗

Pentadentate terpyridine-catechol linked ligands and their cobalt(III) complexes.

A series of novel pentadentate terpyridine-catechol linked ligands were prepared, in which the terpyridine and catechol moieties were linked together by (CH2)n chains of different lengths (n = 4-6). Together with 1-methylimidazole, these ligands formed low-spin, six-coordinate Co(III) complexes. Two of the complexes (n = 4, 5) were characterized by X-ray crystallography [n = 4, monoclinic, P2(1)/c, a = 14.957(7) A, b = 10.585(9) A, c = 23.033(7) A, beta = 106.01(3) degrees, V = 3505(3) A3, Z = 4, R = 0.063; n = 5, monoclinic, P2(1)/c, a = 8.848(7) A, b = 15.78(1) A, c = 25.455(7) A, beta = 93.90(5) degrees, V = 3544(3) A3, Z = 4, R = 0.056], which revealed similar structures around the Co(III) centers but different conformations for the (CH2)n linkers. The (CH2)4 linker showed a straight, symmetric conformation whereas the (CH2)5 linker showed a curved conformation that allowed the accommodation of one extra CH2 unit, suggesting that the (CH2)4 linker presents the "best-fit" length for these complexes.

Journal Article↗

Substrate specificities of rabbit lung and porcine liver flavin-containing monooxygenases: differences due to substrate size.

Phenothiazine, 2-(trifluoromethyl)phenothiazine, and a series of 10-(N,N-dimethylamino-alkyl)-2-(trifluoromethyl)phenothiazines with alkyl side chains varying in length from C2 to C7 were tested for substrate activity with purified rabbit lung and porcine liver flavin-containing monooxygenases (FMO). While all were substrates for the hepatic FMO, only phenothiazines bearing C6 and C7 alkyl side chains were oxidized at significant rates by the pulmonary FMO. Kinetic constants calculated from reaction velocities for the oxidation of thiourea, phenylthiourea, and naphthylthiourea indicate that a nucleophilic heteroatom on the end of a molecule not much larger than a six-membered ring in cross section is oxidized by both enzymes, but the addition of bulky lipophilic substituents increases the Km of N-substituted thioureas for rabbit lung FMO and 1,3-diphenylthiourea (thiocarbanilide) is excluded entirely. From the dimensions of compounds excluded and from those oxidized, it would appear that the hydroperoxyflavin in rabbit lung FMO lies about 6-8 A below the surface in a channel no more than 8 A in diameter in its longest axis. The channel leading to this oxidant in hepatic FMO appears more open and readily admits compounds bearing a tricyclic ring. Differences in dimensions of the substrate channel appear responsible for some of the differences in substrate specificities between liver and lung FMO.

Animals↗

Determination of thiosulfate in body fluids by GC and GC/MS.

A simple and sensitive method to determine thiosulfate in human blood and urine was devised. Thiosulfate was first alkylated with pentafluorobenzyl bromide, with L-ascorbic acid as the stabilizer and sodium chloride as the catalyst. The alkylated thiosulfate was oxidized with iodine to obtain bis(pentafluorobenzyl)disulfide, which was then subjected to gas chromatography and gas chromatography/mass spectrometry. Mass fragmentography was used to identify the disulfide, and gas chromatography with an electron capture detector was used for quantitative determination. The lower limit of detection was 0.003 mumol/mL.

Alkylation↗

Sensitive determination of delta 9-tetrahydrocannabinol in human tissues by GC-MS.

A reliable, simple, and sensitive method was devised to determine the levels of delta 9-tetrahydrocannabinol (THC) in human solid tissues. THC was effectively extracted with acetonitrile, and interfering compounds were removed by washing with a solution of sodium hydroxide and hydrochloric acid. THC was then derivatized by methylation and subjected to gas chromatography-mass spectrometry. Deuterated methyl THC (THC-CD3) was used as an internal standard. The calibration curves were linear in the concentration range from 1 to 100 ng/g, and the lower limit of detection was 1 ng/g in all samples examined. The accuracy and precision of the method were evaluated in every tissue sample at two different concentrations, 5 and 50 ng per sample. The coefficient of variation ranged from 3.4 to 11.6%. We used this method to identify THC in tissues from an autopsied individual, and the distribution of this drug in the tissues was evaluated based on medico-legal criteria.

Adult↗

Capacity to produce cytokines during weight restoration in patients with anorexia nervosa.

OBJECTIVE: Anorexic patients are surprisingly free of infectious complications despite their seriously undernourished state. To study this phenomenon, we longitudinally measured the capacity to produce cytokines in restricting-type anorexic patients. METHODS: Lymphoproliferative responses with phytohemagglutinin (PHA) and the capacity of whole blood to produce cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and granulocyte-colony stimulating factor (G-CSF), were longitudinally measured before and after weight gain, that is, at admission and at less than 60, 65, and 75% of standard body weight (SBW), in 17 patients with restricting-type anorexia nervosa and in 17 control subjects. RESULTS: Cytokine production of IL-1, IL-6, and TNF-alpha per monocyte in the anorexic patients recovered only with the start of refeeding, whereas IFN-gamma production per lymphocyte was similar to that in control subjects and did not change during weight restoration. Only G-CSF production, even at 75% SBW, did not improve during weight restoration. Between the weight at admission and 65% SBW, the increase in the percentage of SBW and improvement of the total protein level were significantly correlated with improvement of the lymphocyte proliferative response with PHA. CONCLUSIONS: The capacity to produce most cytokines recovered with the start of weight gain; however, recovery was not correlated with weight gain. The results suggest that the capacity to produce cytokines in these anorexic patients was dependent on something other than the absolute value of body weight, such as the start of refeeding, the neuroendocrine system, or the autonomic nervous system.

Adult↗

Helical CT in the diagnosis of small bowel obstruction.

With recent technologic developments, the role of computed tomography (CT) in the diagnosis of bowel obstruction has expanded. CT is recommended when clinical and initial radiographic findings remain indeterminate or strangulation is suspected. This modality clearly demonstrates pathologic processes involving the bowel wall as well as the mesentery, mesenteric vessels, and peritoneal cavity. CT should be performed with intravenous injection of contrast material, and use of thin sections is recommended to evaluate a particular region of interest. CT is reported to have a sensitivity of 78%-100% for the detection of complete or high-grade small bowel obstruction but may not allow accurate diagnosis in cases involving incomplete obstruction. In such cases, the use of adjunct enteroclysis is indicated. Furthermore, multiplanar reformatted imaging may help identify the site, level, and cause of obstruction when axial CT findings are indeterminate. CT can also demonstrate findings that indicate the presence of closed-loop obstruction or strangulation, both of which necessitate emergency exploratory laparotomy. Unfortunately, these pathologic conditions may be missed, and patients with suspected severe obstruction or bowel ischemia in whom CT and clinical findings are widely disparate must also undergo laparotomy. In general, however, CT allows appropriate and timely management of these emergency cases.

Diagnosis, Differential↗

Study of the effects of aging on macromolecular synthesis in mouse steroid secreting cells using microscopic radioautography.

The effects of aging on DNA, RNA and protein synthesis in adrenal gland cortical cells and testicular Leydig cells of ddY mice at various ages (from prenatal day 19 to postnatal days 1, 3, 7, 14, months 1 and 6 and 1 and 2 years after birth) were examined using light and electron microscopic (EM) radioautography after labeling with [3H]-thymidine, [3H]-uridine and [3H]-leucine. The percentage of the labeled cells in the adrenal glands after [3H]-thymidine injection was greatest in the zona glomerulosa of the cortex and the medulla on embryonic day 19, in the zona fasciculata and zona reticularis of the cortex on postnatal day 1 and gradually decreased with aging. EM radioautography revealed that well developed cell organelles such as smooth surfaced endoplasmic reticulum, Golgi apparatus, mitochondria with tubular cristae and lipid droplets were more frequently observed in the cytoplasm of unlabeled cells as compared to cells labeled with [3H]-thymidine in the three zones of the cortex. The effects of aging on RNA synthesis in adrenal glands after [3H]-uridine injection revealed that all types of cells of the adrenal gland were labeled. In each cell, silver grains were localized over the nuclei and cytoplasm and were more dense in the nuclei than the cytoplasm. Grain counts were highest in the cortex and medulla on fetal day 19 and then gradually decreased with aging from postnatal day 14 to 1 year after birth. In the cortex, the number of silver grains was higher in the zona glomerulosa than in the other zones from fetal day 19 to 1 year and grain counts were higher in the medulla in the embryonic stage as compared to the postnatal stages. However, the number of labeled mitochondria and the mitochondrial labeling index increased with aging. The [3H]-thymidine labeling index in the Leydig cells of the testis was low at embryonic and early postnatal stages, increased slightly at 6 months and reached a peak at 9 months which was maintained at a relatively high level in senescence. The number of the silver grains over the nuclei and cytoplasm of Leydig cells due to [3H]-uridine labeling was observed from embryonic day 19 and increased from month 3 onwards. From adult to senescence, [3H]-uridine incorporation was maintained at high levels in the nuclei and was relatively low in the cytoplasm. The effects of aging on [3H]-leucine incorporation in Leydig cells were also examined. The labeling indices between embryonic and early postnatal stages showed no obvious differences although the number of the silver grains in both cytoplasm and nucleus increased from 6 months onwards and was maintained at high levels until senescence. From these results, it was concluded that the effects of aging on DNA, RNA and protein synthesis in steroid secreting cells such as adrenal gland cortical cells and testicular Leydig cells of mice correlated with the hormonal changes observed with aging.

Adrenal Cortex↗

Obstructive jaundice facilitates hepatic metastasis of B16F1 mouse melanoma cells: participation of increased VCAM-1 expression in the liver.

Obstructive jaundice facilitates experimental liver metastasis in the rat model, but the detailed mechanisms of this facilitation remain unclear. This study aimed to evaluate the contribution of vascular cell adhesive molecules-1 (VCAM-1) to augmented hepatic metastasis in cases of obstructive jaundice. Obstructive jaundice was induced in male C57BL/6 mice by common bile duct obstruction for 5 days using a Surgiclip. For the biliary decompression, obstructive jaundice was induced for 5 days, followed by removal of the Surgiclip. Liver specimens and blood samples were obtained from animals 5 days after biliary obstruction (OJ5) or sham operation and 2, 5, 11, 14 days after biliary decompression. The expression of VCAM-1 mRNA was increased in the livers from the OJ5 group. Western blot analysis demonstrated increased expression of VCAM-1 protein in the livers of the OJ5 group, in contrast with low VCAM-1 expression in the sham group. The expression of VCAM-1 protein was sustained at high levels at 2 days and decreased at 5 days after biliary decompression (BD5). For the induction of experimental hepatic metastasis, male C57BL/6 mice were randomized to three groups (sham, OJ5, BD5) of six animals each. B16F1 melanoma cells were introduced into the animals by an intraportal injection. Metastatic colonies in the livers were investigated 13 days after inoculation. The mean number of metastatic colonies was significantly increased in the OJ5 group (70.5+/-51.2) compared to that of the sham group (7.2+/-7.9) (p<0.05). This augmentation of hepatic metastasis was abrogated in the BD5 group (16.8+/-20.3). In conclusion, our results suggest that augmented hepatic metastasis in cases of obstructive jaundice are partly mediated through VCAM-1/VLA-4 interaction.

Animals↗

A field emission SEM and HVTEM study of collagen fiber bundles in the lamina propria of the palatine mucosa in the developing mouse.

The ultrastructural development of the surface belonging to the epithelium-connective tissue interface of the hard and soft palatine mucosa of mouse was studied using field emission scanning electron microscopy and high voltage transmission electron microscopy methods. The tissues were analysed at 18 days of gestation, and, 1, 3, 7, 14, 21, 30 and 90 days after birth. The three-dimensional architecture of the connective tissue in the lamina propria showed different shapes. The papillae began to form on days 7 and 14 but continued to growth until the adult period. Different stages of primary and secondary connective tissue papillae were recognized in the hard palatine mucosa whereas the soft palate showed erect connective tissue papillae, small round formations containing taste buds and several openings of the salivary glands ducts.

Aging↗

Cimetidine enhances the antiproliferative effect of 5-fluorouracil on colon carcinoma SW620.

We investigated the effects of cimetidine on p-glycoprotein and on the antiproliferative effect of various anticancer drugs which are recognized by p-glycoprotein. We used colon carcinoma SW620 cells and their doxorubicin resistant SW620 Ad300 derived cells, the latter express p-glycoprotein and have multidrug resistance phenotype. To assess the effect of cimetidine on the efflux activity of p-glycoprotein, we examined its effects on the accumulation of rhodamine123 which is recognized by p-glycoprotein. Cimetidine had no effect on rhodamine123 accumulation on either cell line. Cimetidine did not enhance the antiproliferative effect of any of the anticancer drugs investigated. This indicates that cimetidine was not recognized by p-glycoprotein. However, cimetidine remarkably enhanced the antiproliferation effects of 5-fluorouracil on SW620 cells, not those of 5-fluorouracil on SW620 Ad300, whereas cimetidine itself showed little effect on antiproliferation. This finding indicates that combination therapy using 5-fluorouracil and cimetidine might be useful for cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[A case of bilateral brachial plexopathy after median sternotomy].

A 53-year-old man with bilateral brachial plexopathy after median sternotomy for cardiac surgery was described. When he was awakened six days after cardiac surgery, he experienced weakness and paresthesia of both upper limbs. Neurological examination revealed moderate to severe atrophy and weakness of right biceps, brachioradialis, left triceps, and distal muscles of both upper limbs, and paresthesia around the right thumb and the left hypothenar. Deep tendon reflex of the right biceps, triceps, brachioradialis and left triceps was absent. In addition, he showed Horner's syndrome at the left side. The results of needle EMG and nerve conduction study indicated the damage of the right upper trunk and left middle and lower trunks of the brachial plexus. Although brachial plexopathy following median sternotomy has previously been reported in Western literatures, there is only a single report of unilateral brachial plexopathy in Japan. This is the first report in Japan of the bilateral brachial plexopathy following median sternotomy, and suggests that brachial plexopathy should be recognized as a complication of median sternotomy.

Brachial Plexus↗

Detection of occult tumor cells in peripheral blood from patients with small cell lung cancer by reverse transcriptase-polymerase chain reaction.

The reverse transcriptase-polymerase chain reaction (RT-PCR) of tumor-specific or -associated genes is a sensitive assay for detecting a minimal number of tumor cells in peripheral blood (PB) or bone marrow (BM). In this study, we determined whether mRNA of bombesin receptors is detectable in PB or peripheral blood progenitor cell (PBPC) samples from patients with small cell lung cancer. Among three bombesin-like peptide receptors, we used the neuromedin B receptor (NMB-R) gene as a target, because of the most frequent expression on SCLC cell lines. The lower limit of detection was one tumor cell in one million normal PB cells and there was no detection in normal PB or BM cells unlike a cytokeratin 19 gene. The NMB-R gene was detected in 14 (31.8%) of 44 PB samples from patients with SCLC at diagnosis and 2 (15.4%) of 13 samples of PBPC collected during a recovery phase after chemotherapy followed by administration of G-CSF (filgrastim). At diagnosis, patients whose PB was positive for the NMB-R gene had a significantly shorter survival than those who were negative. Our observation suggests that this assay may be useful in diagnosing metastatic disease and monitoring minimal residual disease in patients with SCLC.

Aged↗

Prophylactic chemolipiodolization for postoperative hepatoma patients.

BACKGROUND/AIMS: The efficacy of prophylactic chemolipiodolization following hepatic resection in patients with hepatocellular carcinoma was studied. METHODOLOGY: Forty-four of 67 consecutive patients with hepatocellular carcinoma who underwent hepatectomy between 1980 and 1997 were divided into two groups: group A (n = 21), in which prophylactic chemolipiodolization was performed during postoperative follow-up (2.4 times on average using a 39 mg mean dose of epirubicin or doxorubicin); and group B (n = 23), without prophylactic chemolipiodolization. The clinicopathological background and patient survival were compared retrospectively. RESULTS: There were no differences in the clinicopathological background between the two groups. Multiple intrahepatic recurrence was frequently observed in group B (P < 0.02). The recurrence-free survival rates in group A (54.4% and 31.1% at 3 and 5 years, respectively) were significantly higher than those in group B (15.7% and 7.9%, respectively). The survival rates of group A (95.2% and 80.4% at 3 and 5 years, respectively) were significantly higher than those in group B (40.1% and 22.9%, respectively). CONCLUSIONS: Our data suggest that postoperative prophylactic chemolipiodolization can be an effective treatment in reducing intrahepatic recurrence and may prolong survival for hepatocellular carcinoma patients following hepatic resection.

Aged↗

Study on RNA synthesis in the retina and retinal pigment epithelium of mice by light microscopic radioautography.

With the aim of determining the distribution of the incorporation of 3H-uridine in both retina and retinal pigment epithelium (RPE), the mouse eyes at embryonic day 9.5 (E 9.5), E 12.5, E 14.5, E 16.5, E 18.5 of gestational ages, and postnatal day 1 (P 1), P 3, P 7, P 14 were analyzed by light microscopic radioautography. Small pieces of the ocular tissues were labelled with 3H-uridine in vitro and light microscopic radioautographs were prepared. The average grain numbers per cell of the respective regions of tissues were calculated. In the retina, the grain numbers increased gradually from E 9.5 to P 1 and reached the maximal value at P 1, and then decreased until P 14. However, the grain numbers were more in the vitreal portion than those in the scleral portion at E 16.5 and then became more in the scleral portion from E 18.5 to P 14. It is considered that the ganglion and bipolar cells finish the RNA synthesis earlier, while the photoreceptor cells do it later during the fetal and postnatal development. In the RPE, the grain numbers gradually increased from E 12.5 to P 7 and then decreased until P 14. Considering the same ages, the grain numbers increased in the following order, anterior, equatorial and posterior regions during embryonic stages, but decreased in the same order after birth. Therefore, it is suggested that the activity of RNA synthesis in PE cells is higher in the posterior region than in the anterior region during embryonic stages. But the activity ascends generally and becomes relatively higher in the anterior region, after birth. Comparing the retina and RPE, it was noted that the grain numbers in the RPE were more important than in the retina and that the maximal value was at P 1 in the retina, while it was at P 7 in the RPE. From these results, it can be concluded that the RNA synthesis ceases earlier in the retina than in the RPE.

Aging↗

Light microscopic radioautographic study on the DNA synthesis of prenatal and postnatal aging mouse retina after labelled thymidine injection.

The DNA synthesis of mouse retina from the 19th prenatal day through 12 months postnatal has been studied by light microscopic radioautography after the injection of tritiated thymidine. A peak of the labeling index after incorporation of tritiated thymidine was found at fetal day 19. The labelled cells decreased gradually with the developing of the eye from the first postnatal day and were completely disappeared in two weeks after birth. The data also indicated obvious regional differences of the incorporation of tritiated thymidine during the periods of the retina development. The labeling index was the greatest in the anterior region compared to the equator region and the posterior region in the same group of age. The average number of the silver grains in labelled nucleus lead to a decrease with the development of the retina after birth, but there was no significant regional differences found in the same group of age. The data shown from this study suggest that the cell differentiation in mouse retina proceed from posterior to anterior region.

Aging↗

Determination of olaquindox residues in swine tissues by liquid chromatography.

A liquid chromatographic (LC) method is described for determination of olaquindox residues in swine tissues. The drug is extracted from tissues with acetonitrile, and the extract is evaporated to dryness. This residue is cleaned up by alumina column chromatography. LC analysis is carried out on a Nucleosil C18 column, and olaquindox is quantitated by ultraviolet detection at 350 nm. The average recoveries of olaquindox added to tissues at levels of 0.2, 0.1, and 0.05 ppm were 74.0, 68.6, and 66.3%, respectively. The detection limit was 2 ng for olaquindox standard and 0.02 ppm in tissues.

Animals↗