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Biomedical subjects

K Yagi

Publications and source records attributed to K Yagi.

918 records · Page 51Linked to original sources

Anticonvulsive effect of dapsone (4,4'-diaminodiphenyl sulfone) on amygdala-kindled seizures in rats and cats.

Dapsone (4,4'-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated oral administration in cats, relatively higher initial doses (13-23 mg/kg) were required to obtain seizure suppression, and neurotoxic signs occurred within a few days with serum drug levels of approximately 20 micrograms/ml. Although dapsone showed anticonvulsive effects in both animal species, the effective serum levels overlapped the toxic levels reported in the clinical treatment of leprosy. In the majority of the cats, however, seizure suppression was maintained even after the discontinuation of dapsone with lower serum levels than those observed at the beginning of the seizure suppression. Therefore, dapsone would be useful as an antiepileptic drug only when long-term anticonvulsive efficacy is demonstrated using smaller doses comparable to those used in the treatment of leprosy.

Amygdala↗

Intraoperative autologous blood salvage with cardiac surgery: an analysis of five years' experience in more than 3,000 patients.

STUDY OBJECTIVE: To analyze intraoperative autologous salvage of shed mediastinal blood and subsequent transfusion in cardiac surgery. DESIGN: Retrospective statistical analysis. SETTING: University hospital. PATIENTS: Three thousand twenty two patients undergoing cardiac surgery from 1984 to 1988. INTERVENTIONS: A review of anesthesia and transfusion records of all patients who underwent intraoperative salvage of shed blood and autologous transfusion using the Sorenson Receptal Auto Transfusion System (ATS) with saline wash prior to reinfusion in cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The salvaged blood volume ranged from 36 to 2,795 ml, with a mean of 321 +/- 222 ml (SD). Eighteen percent of patients did not receive any homologous blood products during their hospitalization. Patients who received only salvaged autologous transfusion were younger, had higher preoperative hemoglobin and hematocrit values, had a larger body surface area, and had shorter surgeries compared with patients who received only homologous blood or both autologous and homologous blood. More blood products were given to patients who received salvaged autologous blood compared with those who did not. Patients who underwent normovolemic hemodilution prior to extracorporeal circulation with subsequent reinfusion received significantly fewer blood products. Ten preoperative and four intraoperative variables significantly influenced the salvaged volume. Previous cardiac surgery was the most significant preoperative variable, and repair of ventricular septal defect produced by myocardial ischemia was the most significant intraoperative variable. CONCLUSION: Considering the average salvaged volume and its current autologous transfusion-related expense, autologous blood salvage is potentially an economic benefit. Perioperative blood conservation requires a considerable commitment from surgeons, anesthesiologists, perfusionists, and intensive care physicians to be effective.

Blood Substitutes↗

Urinary bone resorption markers in patients with metabolic bone disorders.

Recently, urinary pyridinoline and deoxypyridinoline have been commonly employed as bone resorption markers. We studied these markers in 17 patients with hyperthyroidism, 15 undergoing long-term anticonvulsant drug therapy, and 28 with postmenopausal osteoporosis. Both markers had significantly higher levels than those in age-matched control groups. Values of urinary pyridinoline and deoxypyridinoline correlated well with urinary hydroxyproline levels in patients with hyperthyroidism (r = 0.856, p < 0.001 for pyridinoline and hydroxyproline; r = 0.919, p < 0.001 for deoxypyridinoline and hydroxyproline); however, poor correlations were observed, especially between urinary deoxypyridinoline and urinary hydroxyproline (r = 0.357, NS) in patients with postmenopausal osteoporosis. To compare the discriminatory ability of urinary pyridinoline and deoxypyridinoline, receiver operating characteristic (ROC) curves were generated for each of these patient groups using data from age-matched healthy females as the control group. The areas under the curves for both markers were 100.0% in hyperthyroidism. The areas under the curves for pyridinoline in patients undergoing long-term anticonvulsant drug therapy (mean +/- SE; 98.1 +/- 2.8%) and postmenopausal osteoporosis (77.9 +/- 5.7%) were significantly higher than those for deoxypyridinoline in anticonvulsant drug therapy (92.4 +/- 3.3%) and in osteoporosis (64.9 +/- 4.3%). Using data from premenopausal healthy females as the control group, areas under ROC curves for urinary pyridinoline (100.0%) and deoxypyridinoline (94.8 +/- 5.9%) were significantly higher than those for urinary hydroxyproline (73.8 +/- 9.4%) in patients undergoing long-term anticonvulsant drug therapy. In patients with postmenopausal osteoporosis, those for urinary pyridinoline (97.0 +/- 2.8%) were also significantly higher than those for urinary hydroxyproline (74.0 +/- 6.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stimulatory effect of PACAP on gastroduodenal bicarbonate secretion in rats.

The effects of pituitary adenylate cyclase activating polypeptides (PACAPs) on gastroduodenal HCO3- secretion were investigated in anesthetized rats and compared with those of vasoactive intestinal polypeptide (VIP). Under urethane anesthesia, a rat stomach mounted in an ex vivo chamber (in the absence of acid secretion) or a rat proximal duodenal loop was perfused with saline, and the HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Intravenous injection of PACAP-27 stimulated HCO3- secretion in a dose-dependent manner in the duodenum but not in the stomach; at 8 nmol/kg PACAP-27 increased the HCO3- secretion to maximal values of four times greater than basal levels, although this peptide had no effect on duodenal HCO3- secretion after intracisternal administration (1 nmol/rat). PGE2 (300 micrograms/kg, iv) significantly increased HCO3- secretion in both the stomach and the duodenum. The potency of duodenal HCO3- secretory action was in the following order; PACAP-27 > PACAP-38 = VIP, and that of PACAP-27 was about 100-fold greater than that of PGE2. The duodenal HCO3- secretory action of PACAP-27 as well as PGE2 was markedly potentiated by prior administration of isobutylmethyl xanthine (10 mg/kg, sc), the inhibitor of phosphodiesterase. Folskolin (250 micrograms/kg, iv), the stimulator of adenylate cyclase, also increased HCO3- secretion in the duodenum but not in the stomach. These results suggest that: 1) PACAPs are potent stimulators of HCO3- secretion in the duodenum but not in the stomach; 2) this action is mediated by cAMP through stimulation of adenylate cyclase; 3) cAMP is a mediator in duodenal but not gastric HCO3- secretion; and 4) PACAPs may be involved in the peripheral regulation of duodenal HCO3- secretion.

1-Methyl-3-isobutylxanthine↗

Imaging of various surface properties of fluorescently labelled phospholipid Langmuir-Blodgett films with a combined scanning probe microscope.

We present results of phase separation of a single-component system of 1,2-dihexadecanoyl-sn-glycero-3-phospho-[N-(4-nitrobenz)-2-oxa-1,3-diazolyl]ethanolamine in which a liquid-condensed (LC) phase co-exists with a liquid-expanded (LE) phase. Domain formation in the co-existence region was studied using a newly developed combined scanning near-field optical microscope-atomic force microscope (SNOM-AFM). We demonstrate for the first time that the topographic, friction, fluorescence and surface potential distributions for a phase-separated single-component Langmuir-Blodgett film between the LE and LC phases can be simultaneously observed using the SNOM-AFM with a thin-step etched optical fibre probe.

Fluorescent Dyes↗

An analytic study of epileptic falls.

The subject of this study was a total of 48 epileptic falls or drop attacks in 15 children, captured by a self-tracking video monitoring system. A fall was defined as a complete loss of the maintenance of either standing or sitting posture, which took place within 1 s. The patients with epileptic falling attacks thus defined fulfilled the diagnostic criteria of Lennox-Gastaut syndrome. Through precise analysis of the ongoing sequence from the onset to the completion of the fall, it was possible to classify them into the following four types: (a) tonic type, 9 falls in five patients; (b) flexor spasms type, 25 falls in eight patients; (c) myoclonic-atonic type, 12 falls in three patients; and (d) atonic type, 2 falls in one patient. In contrast to the generally accepted view, it was found that atonic or myoclonic-atonic falls were rather exceptional. Seven of eight children whose falls were categorized as the flexor spasms type, which is reminiscent of infantile spasms in terms of clinical as well as EEG expressions, in fact experienced in their individual history West syndrome before it evolved to Lennox-Gastaut syndrome. In particular, the extreme pathophysiological complexity of epileptic falls or drop attacks is stressed.

Adolescent↗

Clinicoelectrographic concordance between monozygotic twins with severe myoclonic epilepsy in infancy.

Clinical features of a pair of monozygotic male twins, both with severe myoclonic epilepsy in infancy (SME), are described. They were almost completely concordant with respect to seizure onset, clinical seizure symptomatology, interictal, and ictal EEG expressions and seizure prognosis. The existence of such twins suggests the possibility that a genetic factor is determinant in the etiology of this particular epileptic syndrome.

Adult↗

Complex partial status epilepticus provoked by ingestion of alcohol: a case report.

A 27-year-old man had a 5-year history of a peculiar state characterized by clouded consciousness provoked by ingestion of alcohol. The episode was identified electroclinically as nonconvulsive status epilepticus and was activated by ingestion of alcohol. Single-photon emission computed tomography (SPECT) examination during the nonconvulsive status epilepticus showed increased regional cerebral perfusion in the right frontal region. This finding, along with the EEG expressions, supports a cortical origin of the nonconvulsive status epilepticus and a diagnosis of complex partial status epilepticus (CPSE). To our knowledge, this is the first report of a documented case of CPSE during intoxication provoked by alcohol ingestion and also of a SPECT examination during CPSE.

Adult↗

Evidence of secondary epileptogenesis in amygdaloid overkindled cats: electroclinical documentation of spontaneous seizures.

Twenty-four spontaneously occurring convulsive seizures were documented by closed-circuit TV (CCTV)-EEG monitoring in 3 cats subjected to unilateral amygdaloid overkindling for < or = 2 years. Electroclinical manifestations suggested that the seizures originated in the kindled amygdala (AM) (10 seizures in 3 cats), contralateral AM (7 seizures in 3 cats), or ipsilateral frontal cortex (7 seizures in 1 cat). All seizures of AM origin except one occurred during sleep 23 h to 20 days after the last stimulation-induced kindled seizure and culminated in secondarily generalized seizures. The seizures of frontal cortical origin occurred during waking within 1 h of a kindled seizure and remained partial in nature. In seizures of AM origin, ictal patterns at the primary and secondary sites were mirror images of each other, but latency of onset of each seizure stage in seizures of secondary site AM origin was longer than that in seizures of primary site AM origin in 2 of the 3 animals. We conclude that the secondary epileptogenic functional alterations capable of producing clinical seizures do occur in AM-overkindled cats, but the seizures are not entirely independent of the primary kindled site.

Amygdala↗

Experimental and clinical studies on liver regeneration following transcatheter portal embolization.

BACKGROUND/AIMS: We studied compensatory hypertrophy following transcatheter portal embolization experimentally in dogs and clinically under the condition of cholestasis. METHODOLOGY: Experimental study: Sixteen dogs were used for this study. Transcatheter portal embolization was performed in the left lobes (70% of the total liver) using Gelfoam powder in dogs with 2-week obstructive jaundice. Liver weight, liver blood flow and the intracellular adenosine triphosphate content of isolated hepatocytes were measured after transcatheter portal embolization. Clinical Study: transcatheter portal embolization of the right portal branch was performed in 13 patients with cancer of the biliary tract and 3 patients with hepatocellular carcinoma before (extended) right lobectomy, using Gelfoam powder and thrombin. Six patients who had a total bilirubin level > 5 mg/dLunderwent a percutaneous transhepatic biliary drainage before transcatheter portal embolization. Liver function tests, a volumetric study with computed tomography and immunohistochemical staining for profilerating cell nuclear antigen and apoptosis in the resected livers were performed. RESULTS: Experimental study: The weight ratio of the non-embolized lobes to the total liver, 2 weeks after transcatheter portal embolization in the dogs with jaundice, was significantly lower than that of the normal dogs with transcatheter portal embolization (40.5 +/- 4.5% vs. 47.6 +/- 3.2%), but significantly larger than that of the dogs without transcatheter portal embolization. The cellular adenosine triphosphate content and tissue blood flow in the embolized lobes were significantly lower than those in the nonembolized lobes in the normal and cholestatic livers. Clinical study: The postoperative course in all patients was uneventful, with no serious complication or liver dysfunction. Extended right lobectomy with caudate lobectomy was equivalent to 65% before transcatheter portal embolization and to 56% after, transcatheter portal embolization owing to compensatory hypertrophy of the left lobe. However, there was no significant difference in liver volume in the patients with or without obstructive jaundice. Apoptosis was observed in the embolized lobe. CONCLUSIONS: Preoperative transcatheter portal embolization with percutaneous transhepatic biliary drainage for the purpose of liver regeneration would be useful for treating extended hepatectomy with obstructive jaundice.

Animals↗

Effects of interferon-beta in combination with 5-fluorouracil on the growth of esophageal cancer cells in vitro.

The possible antiproliferative potency of human recombinant interferon-beta (hIFN-beta) towards ten human esophageal cancer cell lines was examined in comparison with the activity of the factor towards human malignant melanoma cell lines. The cell growth of esophageal cancer cell lines was inhibited by hIFN-beta in a dose- and time- dependent manner. The 50% inhibitory concentrations (IC50) of hIFN-beta on nine cell lines out of ten ranged between 23 to 332 IU/ml of culture medium. The remaining cell line, T.Tn, was less sensitive to the interferon (IC50, 611 IU/ml). Under the same culture conditions, the melanoma cell lines tested differed markedly in their sensitivity to hIFN-beta. When the esophageal cancer cells were treated with 5-fluorouracil (5-FU) in the presence of a low concentration of hIFN-beta, the effectiveness of 5-FU was markedly enhanced. In particular, the rate of growth inhibition of T.Tn cells was more than the added potencies of 5-FU and hIFN-beta indicating that the interferon is an effective biomodulator of 5-FU. All these data suggest that combination therapy with hIFN-beta and the anticancer drug 5-FU would be beneficial for the treatment of carcinoma of the esophagus.

Antineoplastic Combined Chemotherapy Protocols↗

The micronucleus test using peripheral blood reticulocytes from methotrexate-treated mice.

The induction of micronuclei by methotrexate (MTX) was examined in two laboratories using mouse peripheral blood reticulocytes. MTX was a weak inducer in the micronucleus test using bone marrow cells and single treatments, and was one of the few chemicals showing a multiple-treatment effect (CSGMT/JEMS.MMS, 1990). In our preliminary experiments, the ratio of reticulocytes to total erythrocytes decreased greatly after a single treatment with MTX at 100 mg/kg, so lower dose levels of MTX were selected to carry out the micronucleus test in peripheral blood. Full-scale tests were performed at dose levels of 0, 10, 20, 40, and 80 mg/kg, with five sampling times of 0, 24, 48, 72, and 96 h. Frequencies of micronucleated reticulocytes (MNRETs) increased dose-dependently at 72 h, to a maximum of approximately 1%; some preparations obtained from the animals at higher doses could not be examined because the ratio of reticulocytes to total erythrocytes had decreased severely. At doses of 0.5-4.0 mg/kg, the effect of multiple treatments vs. single treatments was not clear, nor was the maximum level of response much different. Since MTX induced a clear positive response in peripheral blood reticulocytes after a single treatment, the reticulocytes in peripheral blood seem a more sensitive target.

Acridine Orange↗

Restored activation of primary motor area from motor reorganization and improved motor function after brain tumor resection.

BACKGROUND AND PURPOSE: Reorganization of brain function may result in preservation of motor function in patients with brain tumors. The goal of the present study was to investigate whether function of the primary motor area (M1) was restored and whether motor function improved after brain tumor resection. METHODS: Five patients with metastatic brain tumors located within or near M1 underwent awake surgery with intraoperative cortical mapping and continuous task monitoring. Preoperative and postoperative functional MR imaging (fMRI) was performed during hand clenching, and diffusion tensor imaging (DTI) was performed in 1 case to further characterize the area activated in fMRI. RESULTS: Preoperative fMRI performed during hand clenching demonstrated reorganization of motor function. In patients with severe paresis (cases 3, 4, and 5), clenching of the affected hand induced a large blood oxygen level-dependent response in the right hemisphere, mainly in the anterior temporal lobe, despite the location site of the tumor. Postoperative fMRI during hand clenching demonstrated activation of the contralateral M1. Furthermore, in case 5, DTI detected tracts, possibly the inferior longitudinal fasciculus, arising from anterior temporal activated area as well as tracts connecting the premotor and M1 activated area. This patient demonstrated mirror movement of the hand during the course of motor function recovery. CONCLUSIONS: Tumor resection resulted in restoration of M1 function and improved motor function in patients with preoperative reorganization of M1 function. Furthermore, the preoperative reorganization of motor function in cases with severe paresis may be related to changes in the right hemisphere, including the temporal lobe.

Aged↗

Alteration of the substrate specificity of Aspergillus oryzae beta-galactosidase by modification with polyethylene glycol.

beta-Galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) purified from Aspergillus oryzae was modified with 2,4,6-trichloro-s-triazine derivatives of polyethylene glycol (activated BPEG) having molecular weights of 600, 1500, 2000, and 4000. Polyethylene glycol derivatives were attached to 6 of the 12 amino groups exposed on the surface of the enzyme. Upon modification, the enzymatic activity for a water-soluble substrate, o-nitrophenyl beta-D-galactopyranoside, was reduced with increasing molecular weight of the activated BPEG. On the contrary, the enzymatic activity for another substrate, 4-methylumbelliferyl beta-D-galactopyranoside, was increased upon modification. The Michaelis constants of native and modified enzymes for these two substrates were virtually the same. The effect of the modification was more marked in the enzymatic hydrolysis of the beta-galactosidic bond of amphipathic substrates. A fluorescent analog of naturally occurring galactocerebroside, 1-O-galactosyl-2-N-(1-dimethylaminonaphthalene-5-sulfonyl)-sphingosine, was hydrolyzed more rapidly by the modified enzyme than by the native one. The enzyme modified with activated BPEG of 1500 Da had the highest activity for this substrate. The beta-galactosidic bond of the terminal galactose of GM1-ganglioside (II3NeuAcGgOse4Cer, galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminosyl)-galactosyl -glucosylceramide) was cleaved by the modified but not by the native enzyme.

Aspergillus↗

Effects of gamma-ray irradiation on superoxide dismutase activity and lipid peroxide level in mouse salivary glands.

The effect of local gamma-ray irradiation on the enzymatic activity of superoxide dismutase in salivary glands was examined. Mice received a single dose of 60Co gamma-ray irradiation in the range of 3 to 24 Gy to their neck regions. The enzymatic activity in salivary glands was decreased significantly at the 7th day and almost recovered at the 14th day after irradiation with over 6 Gy. The elevation of the lipid peroxide levels in the submandibular gland followed by the leakage of superoxide dismutase from the glands into the blood plasma was observed after irradiation, indicating radiation-induced membrane damage of salivary glands.

Animals↗

Separation of nucleotides by high-voltage capillary electrophoresis.

A new separation method using high-voltage capillary electrophoresis was applied to the analysis of several nucleotides. This system consisted of a micro-bore glass capillary column of 80-micron i.d., a high-voltage power supply, and a uv detector set at 254 nm. Seven nucleotides (cyclic AMP, AMP, ADP, ATP, GMP, GDP, and GTP) were separated completely from each other in 0.02 M phosphate buffer (pH 7) containing 0.5% ethylene glycol by applying about 150 V/cm. The theoretical plate number for AMP was nearly 45,000. A good separation of nucleotides in biological samples of rat blood, liver, and kidney was attained under the same conditions as above. Concentrations of nucleotides in these biological samples were measured by using pyridoxamine as an internal standard.

Animals↗

Cationic multilamellar liposome-mediated human interferon-beta gene transfer into cervical cancer cell.

Interferons (IFNs) have antineoplastic activity, but it has been reported that treatment with IFN alone is not effective in many cancers. To enhance the effect of growth inhibition on tumor cells by raising the concentration, we attempted the transfection of cervical cancer cells, HeLa cells, with human interferon-beta (HuIFN-beta) cDNA contained in the expression vector pRSV delivered by cationic multilamellar liposomes, which resulted in the secretion of HuIFN-beta into the medium. The concentration of HuIFN-beta in the medium was 22 IU/ml by 72 hours after transfection of 10 ng DNA, and provoked around 45-fold cell growth inhibitory effect compared with that of exogenously added HuIFN-beta (1000 IU/ml). This strong growth inhibition was considered to be due to the action of HuIFN-beta in a paracrine manner, and a notable fraction of the cell death was apoptotic.

Apoptosis↗