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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 253 records · Page 14Linked to original sources

A dynamic change by 123I-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid myocardial single photon emission computed tomography in a 55-year-old woman.

A 55-year-old woman was admitted to hospital with chest discomfort. Emergency angiography revealed no organic stenosis in the coronary artery, but there was akinesis in the apico-anteroseptal region of the left ventricle. Left ventriculography on the 5th day after admission was normal. On the 2nd day, initial imaging by 123I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) indicated a slight decrease in tracer uptake and delayed imaging revealed fill-in in the apicoanteroseptal regions in spite of akinesis in those areas. On the 4th day, initial imaging by 123I-BMIPP showed a moderate decrease in tracer uptake and delayed imaging revealed a high washout again in those areas. On the 12th day, initial imaging by 123I-BMIPP showed a severely reduced uptake in the apico-anteroseptal regions and delayed imaging disclosed a high washout, in the same areas that showed akinesis during the acute phase. On the 35th day, 123I-BMIPP identified no significant decrease in tracer uptake. It is suggested that these dynamic changes in 123I-BMIPP myocardial SPECT imaging may reflect the metabolic change of fatty acid in the ischemic state, the size and degree of turnover of the triacylglycerol pool.

Fatty Acids↗

Bacterial expression and functional characterization of a rat thyroid hormone sulfotransferase, ST1B1.

At least three forms of phenol sulfotransferase (ST) ST1B1, ST1A1 and ST1C1 are contained in rat livers. To identify the form contributing to the metabolism of 3,3',5-triiodothyronine (T3), functional characterization of these forms was performed by expression in Escherichia coli. ST1B1 and ST1C1 were shown to be active on sulfation towards T3 with high affinity (Km: 44.4 and 25.8 microM, respectively), whereas ST1A1 had low affinity. In Western blotting using antibodies raised against the individual ST, hepatic contents of each ST were quantitatively determined. ST1B1 showed no clear sex-difference, whereas the level of ST1C1 was higher in adult males than adult females. The content of ST1B1 was 1.4, 6.8 and 10 times higher than that of ST1C1 in adult males, adult females and both sexes of immature rats, respectively. The developmental pattern of ST1B1 was similar to that of ST1A1, but differed from that of ST1C1. These results indicate that ST1B1 and ST1C1 are involved in T3 metabolism in rats and ST1B1 is the constitutive form across sexes and ages.

Amino Acid Sequence↗

Alteration of hepatic sulfation by endotoxin.

Administration of an endotoxin, lipopolysaccharide (1 mg/kg body weight), caused decreases in hepatic sulfations of xenobiotics in male rats through changes in the amounts of at least three forms of sulfotransferases, ST1A1, ST1B1 and ST1C1. The time-dependent decrease was first observed with ST1B1, followed by ST1A1 and ST1C1; and the decrease was more profound in the levels of mRNAs than those of proteins. The decreases in their mRNAs were, however, prevented by the pretreatment with dexamethasone. These results suggest that the endotoxin suppresses the hepatic sulfation through a cytokine-mediated mechanism to change individually hepatic levels of ST1A1, ST1B1 and ST1C1.

Animals↗

Mesh-and-glue technique to prevent leakage of cerebrospinal fluid after implantation of expanded polytetrafluoroethylene dura substitute--technical note.

Expanded polytetrafluoroethylene (ePTFE) can be used as a dura substitute but is associated with leakage of cerebrospinal fluid (CSF) through the suture line. Fibrin glue alone may not prevent this problem. This new method for sealing the suture line in ePTFE membrane uses an absorbable polyglycoic acid mesh soaked with fibrinogen fluid placed on the suture line. Thrombin fluid is then slowly applied to the wet mesh, forming a large fibrin membrane reinforced by the mesh over the suture line. Only one of 33 patients in whom this technique was used had CSF leakage, whereas 12 of 59 patients in whom a dural defect was closed with ePTFE alone showed postoperative subcutaneous CSF collection (p < 0.05). Our clinical experiences clearly show the efficacy of the mesh-and-glue technique to prevent CSF leakage after artificial dural substitution. Mesh and glue can provide an adequate repair for small dural defect. The mesh-and-glue technique may also be used for arachnoid sealing in spinal surgery.

Biodegradation, Environmental↗

Efficacy of aquatic exercises for patients with low-back pain.

We have studied 35 patients (25 female and 10 male) with low-back pain who were managed with aquatic exercises after an appropriate period of treatment for their condition in the medical institution. The exercises employed consisted of strengthening exercises for the abdominal, gluteal, and leg muscles, stretching of the back, hip, hamstrings, and calf muscles, walking in water, and swimming. All the patients had been participating in the exercise program for more than 6 months. The frequency of performing exercises was once a week for 7 patients, twice a week for 19, and 3 or more times a week for the remaining patients. The method used in this study was a survey questionnaire which was composed of questions about the patient's physical and psychological condition. Those patients who had performed exercises twice or more in a week showed a more significant improvement in the physical score than those who performed exercises only once a week. More than 90% of the patients felt they had improved after 6 months of participation in the program. The improvement in physical score was independent of the initial ability in swimming. The results obtained suggested that exercises in water may be one of the most useful modes of exercise for a patient with low-back pain.

Adult↗

[Analysis of elderly patients, aged 60 years old or over, with acute lymphoblastic leukemia].

In order to obtain the realistic background information on clinical features, and the present status of treatment and outcome in elderly patients with acute lymphoblastic leukemia (ALL), we carried out random survey of patients with ALL aged 60 or over who had been admitted to 13 general hospitals in the Nagoya region from January 1990 through December 1995. Among the 20 cases collected, ages ranged from 60 to 88 (median age 68), and the male to female ratio was 11:9. Nineteen cases were L2 subtype in FAB classification. Among 17 patients, 13 had B cell series surface phenotypes (76%), 2 had T cell series (12%), one had stem cell type (6%) and one had an undetermined phenotype (6%). Ph chromosomes were detected in 4 cases among 15 analyzed (27%), whereas 5 were found to have no chromosomal abnormality. Half of the patients had some concurrent disease at diagnosis, including two with treatment-limiting complications. Common induction regimens were the combination of adriamycin (ADM) + vincristine (VCR) + cyclophosphamide (CPM) + mitoxdn trone + L-asparaginase [4 patients]. ADM + VCR + PSL [4 patients]. VCR + PSL [4 patients] and others [8 patients]. The overall remission rate was 55.0% (11/20) without any significant difference according to age. The median survival time (MST) for all cases was 205 days. (1-year survival rate:17.9%, 2-year survival rate:10.8%). There was no significant difference in survival times among patients with the Ph chromosome, those with other chromosomal abnormalities and those without them. All the patients aged 75 or over were treated with attenuated induction therapy, and they had a shorter survival than those aged less than 75, but with no statistical significance [MST:121 days versus 276 days, p = 0.307 (generalized Wilcoxon test)].

Aged↗

The mechanism of the increasing action of TA-993, a new 1,5- benzothiazepine derivative, on limb blood flow in anesthetized dogs: selective suppression of sympathetic nerve activity.

TA-993, (-)-cis-3-acetoxy-5-(2-(dimethylamino)ethyl)-2, 3-di-hydro-8-methyl-2-(4-methylphenyl)-1,5-benzothiazepin-4(5H)one maleate, a new 1,5-benzothiazepine derivative with l-cis configuration, has a unique and selective increasing action on limb blood flow with little influence on arterial pressure besides an antiplatelet action. We studied the mechanism of increasing action of TA-993 on limb blood flow in anesthetized dogs. In a canine blood-perfused hindlimb preparation with a donor dog, TA-993 (100 microg/kg i.v.) did not increase femoral blood flow when administered to the donor dog, but did when administered to a recipient dog. TA-993 did not show the increasing action on femoral blood flow in the presence of hexamethonium or phentolamine, whereas it did in the presence of propranolol or atropine. TA-993 also showed a weak increasing effect on heart rate, which was inhibited by any one of these blockers. TA-993 (300 microg/kg i.v.) did not alter the phenylephrine (1-100 ng/kg i.a.)- or the talipexole (3-100 ng/kg i.a.)-induced increase in perfusion pressure in an autoperfused hindlimb. These results suggest that the increasing action of TA-993 on limb blood flow is mediated by the sympathetic nervous system but that the adrenergic receptors are not likely to be the central point of action of this new agent. There is a possibility that the mechanism of the increasing action on heart rate is different from that of its increasing action on limb blood flow.

Animals↗

[The usefulness of 123I-BMIPP myocardial SPECT in diagnosis for silent myocardial ischemia induced by vasospasm].

This study was designed to evaluate the clinical usefulness of 123I-BMIPP myocardial SPECT in patients with silent myocardial ischemia induced by vasospasm. Ultrasonic echocardiography (UCG), Holter electrocardiogram recording (Holter ECG), exercise 201Tl myocardial SPECT (EX-Tl) and rest 123I-BMIPP myocardial SPECT (BMIPP) were performed in 8 patients with asymptomatic vasospasm without history of myocardial infarction. The sensitivity of each modality in detecting coronary artery spasm was 37.5% (3 of 8 cases) for UCG, 37.5% (3 of 8 cases) in Holter ECG, 25.0% (2 of 8 cases) in Ex-Tl, 62.5% (5 of 8 cases) on initial BMIPP images and 75.0% (6 of 8 cases) on delayed BMIPP images. Severity of regional left ventricular wall motion abnormality in UCG correlated with the severity of regionally decreased tracer uptake in BMIPP. The washout rate of BMIPP was 18.7 +/- 2.4 in normal controls, 32.4 +/- 5.9 in asymptomatic vasospasm, and 38.2 +/- 4.0 in asymptomatic vasospasm with abnormal left ventricular wall motion. It was suggested that 123I-BMIPP myocardial SPECT might be useful for assessing asymptomatic vasospasm.

Adult↗

Effects of the oxadiazine insecticide indoxacarb, DPX-MP062, on neuronal nicotinic acetylcholine receptors in mammalian neurons.

The effects of the novel oxadiazine insecticide DPX-MP062 and its metabolite (DCJW) on neuronal nicotinic acetylcholine receptors (AChRs) were investigated using the whole-cell patch clamp technique in rat embryonic cerebral cortical neurons in primary culture. DPX-MP062, applied at concentrations of 1 and 10 microM to the bath, reduced the peak amplitude of ACh-induced, rapidly decaying currents to 46.8+/-8.8% (n=9) and 15.7+/-5.0% (n=4) of the control, respectively. The effect was irreversible after washing with drug-free solution. DCJW at either 1 microM or 10 microM had similar actions but the potency was much less than that of DPX-MP062. The slowly desensitizing currents induced by low concentrations of ACh (0.1-10 microM) were augmented and those induced by high concentrations of ACh (100-1000 microM) were inhibited by 10 microM DPX-MP062 with great acceleration of the current decay in a time-dependent manner. These effects were use independent and reversible after washing with drug-free solution. In contrast, DCJW at 10 microM did not show significant effects on peak amplitude and decay phase of the slowly desensitizing ACh-induced current in cortical neurons. These results indicate that the oxadiazine insecticide DPX-MP062 has potent modulating actions on neuronal nicotinic AChRs. The neuronal nicotinic AChR could be one of the primary target sites of the insecticide in mammals.

Acetylcholine↗

[A case with traumatic internal carotid artery dissection in which the extent of the pseudolumen was defined by MR angiography].

We report a 29-year-old male with traumatic internal carotid artery (ICA) dissection who presented with cerebral ischemia developed after removal of a left acute subdural hematoma and external decompression. CT scans 4 days after the operation showed infarctions of the distribution of the bilateral cerebral hemispheres. Cerebral angiography on the 11th hospital day demonstrated narrowing of the extracranial internal carotid artery at C1-C2 vertebral levels. Slight arterial dilatation and retention of the contrast medium were found just above the narrowing segment, which was suspected to be a pseudolumen. Three D time-of flight MRA showed an intramural hematoma corresponding to the narrowing on the angiography. Original axial MRA images showed that narrowing of the lumen was surrounded by a crescent hematoma and that two flow velocity areas were in the area distal to the narrowing. High flow seemed to be ordinary artery flow rate. The low flow area, including turbulent flow, led to the retention of contrast medium mimicking a pseudolumen. Precise MRA imaging will bring us an accurate diagnosis of extracranial carotid dissections.

Adult↗

[Mesh and glue technique as a new sealing technique for the use of expanded polytetrafluoroethylene dura substitute: the experimental studies of its tolerance for pressure and long-term histological changes].

Expanded polytetrafluoroethylene (ePTFE) as a dural substitute is sometimes associated with leakage of cerebrospinal fluid through the suture line. We have developed a new technique to seal the suture line with an absorbable mesh and fibrin glue. It is named as the mesh-and-glue technique. In this paper, the basic background of the efficacy of this technique was examined using in vitro and in vivo experimental models. The sealing effect was estimated on water leakage through 1 cm of suture line on the ePTFE sutured with 4-0 braided nylon at intervals of 2mm. The burst pressure of the non-sealed, conventional fibrin glue, simple glue spray, mesh-and-glue, and mesh-and-glue combined with spray was 2.8 +/- 0.4, 4.3 +/- 1.2, 64.4 +/- 21.4, 142.7 +/- 22.2 and 406.1 +/- 29.7 cm H2O respectively. It was worth noting that mesh-and-glue combined with the spray method can tolerate even arterial pressure. It was also observed that mesh-and-glue can seal a small dural defect. Long-term pathological changes of the mesh-and-glue was examined in a murine craniotomy model. Implanted mesh and fibrin glue was gradually transformed into a tight connective tissue firmly adhering to the surrounding structure within two months. These experimental results well support the clinical efficacy of the mesh-and-glue technique. This technique can also be applied to seal the arachnoid membrane after spinal surgery or to seal the suture line of arteriotomy in carotid endoarterectomy.

Animals↗

Acute myeloid leukemia in the elderly:--159 Nagoya case studies--Nagoya Cooperative Study Group for Elderly Leukemia.

To obtain background information on elderly acute myeloid leukemia (AML), unselected data covering 159 patients aged 60 years or over with AML from 14 hospitals in Nagoya, Japan was analyzed retrospectively. Among these patients, 119 had de novo acute AML, 32 had AML which evolved from myelodysplastic syndrome (MDS-AML), and 8 had other types of leukemia. The survey showed that MDS-AML tended to be more prevalent in patients aged 70 years and older and that MDS-AML showed a significantly more severe degree of leukopenia and anemia than de novo AML. MDS-AML also showed a significantly lower complete remission (CR) rate than that of de novo AML [6.9% (2/29) vs 58.3% (67/11), P < 0.01] and significantly shorter survival times than those of de novo AML [median: 3.6 months vs 9.6 months, P < 0.01 (generalized Wilcoxon test; GW]. In de novo AML, the proportion of patients treated with conventional therapy (CT group) decreased significantly, and that of those with attenuated therapy (AT group) increased significantly as age elevated (P < 0.01). The CT group showed a significantly higher CR rate (65.4% vs 41.2%, P < 0.05) and a significantly longer survival period than those of the AT group [median: 11.6 months vs 4.8 months, P < 0.05 (GW)]. Overall survival rates of the older age groups became significantly shorter with aging [P < 0.01 (GW)].

Acute Disease↗

Template activating factor-I remodels the chromatin structure and stimulates transcription from the chromatin template.

To study the mechanisms of replication and transcription on chromatin, we have been using the adenovirus DNA complexed with viral basic core proteins, called Ad core. We have identified template activating factor (TAF)-I from uninfected HeLa cells as the factor that stimulates replication and transcription from the Ad core. The nuclease sensitivity assays have revealed that TAF-I remodels the Ad core, thereby making transcription and replication apparatus accessible to the template DNA. To examine whether TAF-I remodels the chromatin consisting of histones, the chromatin structure was reconstituted on the DNA fragment with core histones by the salt dialysis method. The transcription from the reconstituted chromatin was completely repressed, while TAF-I remodeled the chromatin and stimulated the transcription. TAF-I was found to interact with histones. Furthermore, it was shown that TAF-I is capable not only of disrupting the chromatin structure but also of preventing the formation of DNA-histone aggregation and transferring histones to naked DNA. The possible function of TAF-I in conjunction with a histone chaperone activity is discussed.

Adenoviruses, Human↗

Identification and characterization of N-acetylglucosamine-6-O-sulfate-specific beta1,4-galactosyltransferase in human colorectal mucosa.

6-Sulfo-sialyl Lewis X structure is attributable to recognition between lymphocytes and high endothelial venules. However, the biosynthetic pathway still remains unclear. We found that a beta-galactosyltransferase (betaGalT) in human colorectal mucosa preferentially acts on GlcNAc-6-O-sulfate (6S-GN). 6S-GN:beta4GalT was partially purified by UDP-hexanolamine-Sepharose and asialo-agalacto-ovomucin-Sepharose chromatographies. The optimum pH of this enzyme was found to be 6.5-7.5 and the Michaelis constants for 6S-GN and UDP-Gal were 0.43 mM and 16 microM, respectively. The enzymatic activity was dependent on divalent cations and the substrate specificity was not affected by alpha-lactalbumin. This is the first demonstration of the occurrence of 6S-GN:beta4GalT.

Acetylglucosamine↗

Roles of Rho-associated kinase in cytokinesis; mutations in Rho-associated kinase phosphorylation sites impair cytokinetic segregation of glial filaments.

Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, regulates formation of stress fibers and focal adhesions, myosin fiber organization, and neurite retraction through the phosphorylation of cytoskeletal proteins, including myosin light chain, the ERM family proteins (ezrin, radixin, and moesin) and adducin. Rho-kinase was found to phosphorylate a type III intermediate filament (IF) protein, glial fibrillary acidic protein (GFAP), exclusively at the cleavage furrow during cytokinesis. In the present study, we examined the roles of Rho-kinase in cytokinesis, in particular organization of glial filaments during cytokinesis. Expression of the dominant-negative form of Rho-kinase inhibited the cytokinesis of Xenopus embryo and mammalian cells, the result being production of multinuclei. We then constructed a series of mutant GFAPs, where Rho-kinase phosphorylation sites were variously mutated, and expressed them in type III IF-negative cells. The mutations induced impaired segregation of glial filament (GFAP filament) into postmitotic daughter cells. As a result, an unusually long bridge-like cytoplasmic structure formed between the unseparated daughter cells. Alteration of other sites, including the cdc2 kinase phosphorylation site, led to no remarkable defect in glial filament separation. These results suggest that Rho-kinase is essential not only for actomyosin regulation but also for segregation of glial filaments into daughter cells which in turn ensures correct cytokinetic processes.

Amino Acid Sequence↗

Ion channel modulation as the basis for general anesthesia.

(1) Modulation of the function of the GABA(A) and neuronal nicotinic acetylcholine receptor channels caused by general anesthetics and modulation of the GABA(A) receptor-channel by halothane, enflurane, isoflurane, and n-octanol was channel state-dependent. (3) Halothane modulation of the GABA(A) receptor was independent of subunits, but n-octanol modulation was subunit-dependent. (4) Ethanol at 30-100 microM was very potent in accelerating the desensitization of currents induced by acetylcholine. (5) The ethanol modulation was subunit- and state-dependent, occurring in the alpha3beta4 combination but only weakly in the alpha3beta2 combination. (6) In contrast, halothane at 430 microM (approximately 1 MAC) potently suppressed ACh-induced currents in the alpha3beta2 subunit combination.

Anesthesia, General↗

Stable transfection of retinoblastoma gene promotes contact inhibition of cell growth and hepatocyte nuclear factor-1-mediated transcription in human hepatoma cells.

The retinoblastoma (Rb) gene is a key factor involved in cell cycle regulation. In the present study, alterations in cell growth and expression of the alpha-fetoprotein and albumin genes by the stable transfection of the Rb gene were analyzed in HuH-7 human hepatoma cells. Cell growth was almost similar in the Rb gene-transfected and nontransfected cells at the sparse cell density. However, under a confluent condition, contact inhibition of cell growth was stimulated by the Rb gene transfection. By Northern blotting, the levels of the alpha-fetoprotein and albumin mRNA as well as the transcript of hepatocyte nuclear factor-1 (HNF-1), a liver-specific transcriptional factor regulating both genes, were apparently elevated in the Rb gene-transfected cells, compared with the nontransfected cells. These results suggest that the Rb gene transduction promotes contact growth inhibition in conjunction with the enhanced HNF-1-mediated liver-specific gene transcription in human hepatoma cells.

Carcinoma, Hepatocellular↗