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Biomedical subjects

C Ito

Publications and source records attributed to C Ito.

At least 19 recordsLinked to original sources

Chromosomal localization of the genes encoding the p50/p105 subunits of NF-kappa B (NFKB2) and the I kappa B/MAD-3 (NFKBI) inhibitor of NF-kappa B to 4q24 and 14q13, respectively.

The regulation of expression of a variety of genes involved in immune function, inflammation, and cellular growth control, as well as control of expression of certain viruses such as the human immunodeficiency virus (HIV), is dependent on the transcription factor NF-kappa B. In many cells, NF-kappa B is found in the cytoplasm where it is associated with an inhibitor protein known as I kappa B. Recently the genes encoding the p50 and p65 subunits of NF-kappa B, as well as one form of I kappa B/MAD-3 (NFKBI), have been cloned. As part of our goal to determine the chromosomal organization of members of the REL/NFKB family, as well as their inhibitors, we localized the NFKBp50/p105 (NFKB2) and I kappa B/MAD-3 (NFKBI) genes to human chromosome bands 4q24 and 14q13, respectively.

Chromosome Mapping

Effects of "kyushin", a drug containing toad venom, on experimental congestive heart failure in rabbits.

Effects of "Kyushin" (KY-2), a drug containing toad venom, on a low-output-type heart failure model produced in rabbits by protease treatment on the left ventricular anterior wall, were examined. Heart rate, aortic blood flow (AoF), left ventricular systolic pressure (LVP) and maximal rate of rise of LVP (max dP/dt) in this model were maintained at lower levels than those in normal rabbits, while left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) were maintained at higher levels, and the mean blood pressure (MBP) was at a normal level. KY-2 was administered intraduodenally to the animal. KY-2 improved heart failure state by increasing the AoF, LVP and max dP/dt, and by decreasing the LVEDP and SVR without a significant change in MBP. These results suggest that the beneficial effects of KY-2 on this heart failure model originate from their cardiotonic activity.

Amphibian Venoms

Pharmacological actions of "kyushin," a drug containing toad venom: cardiotonic and arrhythmogenic effects, and excitatory effect on respiration.

The cardiotonic and arrhythmogenic effects, and the excitatory effect on respiration of "Kyushin," a drug containing toad venom, were studied in comparison with those of digoxin. In anesthetized rabbits, the maximum rate of rise of left ventricular systolic pressure (max dP/dt) was measured as an index of cardiotonic effect, and the respiratory flow was measured as an index of respiratory function. Intraduodenal (i.d.) administration of 80 mg/kg "Kyushin" produced a cardiotonic effect and an excitatory effect on respiration, but i.d. administration of 16 mg/kg digoxin produced only a cardiotonic effect, and conversely inhibited respiration. In anesthetized open-chest guinea pigs, myocardial contractile force was measured as an index of cardiotonic effect and the arrhythmogenic effect was evaluated from the appearance of arrhythmic myocardial contraction. By i.d. administration of a 20% ethanol suspension or solution, "Kyushin" and digoxin showed a cardiotonic activity with doses higher than 40 mg/kg and 0.25 mg/kg, respectively. The arrhythmogenic doses of "Kyushin" and digoxin by i.d. administration were 2560 mg/kg and 2 mg/kg, respectively, suggesting that the safety margin of "Kyushin" is broader than that of digoxin.

Amphibian Venoms

[Effects of bufadienolides and some kinds of cardiotonics on guinea pig hearts].

Effects of bufadienolides such as bufalin (BF) and cinobufagin (CB), the main components of Senso (Ch'an Su), on myocardial Na+,K(+)-ATPase activity, the cardiotonic activity in vivo and the action potential of isolated guinea pig papillary muscle cells were compared with those of other cardiotonic drugs. 1) The rank order of potency for inhibition of myocardial Na+,K(+)-ATPase activity was BF greater than digoxin (DG) greater than digitoxin (DT) greater than telocinobufagin greater than gamabufotalin greater than cinobufotalin greater than CB greater than g-strophanthin (GS) greater than digitoxigenin (DTG) greater than resibufogenin (RB) when compared at the 50% inhibitory concentration. 2) In isolated papillary muscle cells, CB shortened the action potential duration (APD) dose-dependently. The order of potency for shortening of APD was GS greater than CB greater than DTG much greater than DT. 3) In open-chest guinea pigs, intraduodenal administration of BF or CB increased the myocardial contractile force (MCF), but did not affect the heart rate. The order of potency for increase in MCF was as follows: methyldigoxin, proscillaridin greater than BF greater than CB greater than DG greater than Senso much greater than DT, DTG, RB. These results indicate that CB has a shortening effect on APD and an inhibitory effect on Na+,K(+)-ATPase activity along with its cardiotonic effect, like GS.

Action Potentials

[Pharmacological effects of Gosha-jinki-gan-ryo extract: effects on experimental diabetes].

Pharmacological effects of Gosha-jinki-gan-ryo extract (KJE) on experimental diabetes induced by cyproheptadine (CPH), aldose reductase activity, and experimental peripheral neuropathy were studied. The effects of KJE were compared with those of Hachimi-jio-gan-ryo extract (HJE). KJE at 417 mg/kg/day (5 times the daily dose in humans) and HJE at 367 mg/kg/day (5 times the daily dose in humans) significantly inhibited the decrease in glucose tolerance by CPH. KJE and HJE inhibited aldose reductase activity, when DL-glyceraldehyde was used as substrate, with IC50 values of 2.68 x 10(-5) g/ml and 4.45 x 10(-5) g/ml, respectively and when D-glucose was used as substrate, with IC50 values of 1.04 x 10(-4) g/ml and 1.55 x 10(-4) g/ml, respectively. KJE at 209 mg/kg/day (2.5 times the daily dose in humans) and HJE at 367 mg/kg/day significantly reduced peripheral neuropathy induced by crushing the sciatic nerve in rats. The potency of these effects of KJE was stronger than that of HJE, when a comparison was made on the basis of the daily dose.

Aldehyde Reductase

Preparation and evaluation of Eudragit gels. I: Eudragit organogels containing drugs as rectal sustained-release preparations.

New organogels containing salicylic acid, sodium salicylate, procaine, and ketoprofen were prepared by using Eudragit L and S, and propylene glycol. The physical properties (e.g., penetration and extensibility) of the organogels were affected considerably by the incorporation of a basic drug, such as procaine, rather than an acidic drug, such as salicylic acid. In in vivo evaluation using rabbits, it was found that 30% Eudragit L organogels containing 1.25% (w/w) salicylic acid or 2.5% (w/w) ketoprofen showed sustained plasma salicylic acid or ketoprofen levels and almost the same AUC as compared with Witepsol H-15 suppositories containing these drugs. Furthermore, the relative bioavailability for salicylic acid and ketoprofen released from 30% Eudragit L organogels, with 10% (w/w) linolic acid or oleic acid as absorption enhancer, increased to 1.55-1.75- and 1.46-1.85-fold, respectively, compared with 30% Eudragit L organogels without these unsaturated fatty acids.

Acrylic Resins

bcl-2 translocation in Japanese B cell lymphoma: novel bcl-2 translocation with immunoglobulin heavy chain diversity segment.

Breakpoints of a lymphoma case with bcl-2 gene rearrangement that did not show comigration of immunoglobulin (Ig) heavy chain joining (JH) fragment were cloned. Sequence analysis revealed that the translocation broke the 3' side of the Ig heavy chain diversity (DH) segment at the heptamer recombination signal and each end was ligated to the bcl-2 locus. Since Southern blot demonstrated that both alleles of JH were rearranged, this translocation was suggested to have occurred at the step of VH-DH, or DH-DHJH recombination, one step later than that of DH-JH recombination where the common pattern of bcl-2 rearrangement generally occurs. Cases that showed comigration with JH fragment were also studied by polymerase chain reaction with 5' bcl-2 oligomer and 3' JH consensus anti-sense oligomer since it has been demonstrated that bcl-2 translocation at the major breakpoint clustering region (mbr) in American cases clusters within an about 150 bp region in the mbr. The results demonstrated that four out of five cases studied were amplified, indicating that the same clustering mechanism exists for Japanese cases. The present study, together with our previous report on Ig kappa-bcl-2, indicated that bcl-2 translocation in Japanese B cell lymphomas might occur at a later stage of B cell development, as compared with that in American cases. Less involvement of bcl-2 in Japanese B cell lymphoma may also be in part explainable by low susceptibility to bcl-2 rearrangement at the step of DH-JH recombination.

Base Sequence

Dual effect of glycine on isolated rat suprachiasmatic neurons.

Pharmacological properties of strychnine-sensitive and -insensitive glycine receptors have been investigated in rat suprachiasmatic nucleus (SCN) neurons. Because the SCN neurons were too small for stable intracellular recordings by the glass-microelectrode technique, a conventional whole cell mode patch-clamp technique was employed on the acutely dissociated SCN neurons. Dissociated SCN neurons were morphologically heterogeneous and could be distinguished into several types. All cells responded to glycine in a concentration-dependent manner. The glycine-induced current was primarily Cl- sensitive and competitively blocked by strychnine. The SCN neurons also responded to excitatory amino acids: glutamate, quisqualate, kainate, and N-methyl-D-aspartate (NMDA). Responses to glutamate and aspartate, which are endogenous neurotransmitter candidates, were enhanced by adding glycine. Glycine especially augmented the maximum response to NMDA in a full concentration range. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not suppress the strychnine-sensitive glycine response but did suppress the strychnine-insensitive NMDA response in a competitive manner for glycine. The results suggest that glycine influences neural activity in the SCN as a classical inhibitory neurotransmitter and an excitatory neuromodulator.

Animals

[Metabolic fate of bufalin in rats].

In an attempt to evaluate the metabolic fate of "Kyushin", which is a traditional medicine containing Toad venom, a 3H-labeled compound of bufalin, which is one of the main active components, has been synthesized. The metabolic fate of the 3H-bufalin was studied after its single and repeated oral administration in rats. After a single administration of the 3H-bufalin (20 micrograms/kg), the radioactivity in the blood reached a maximum level at 15 min. The radioactivity in the blood declined in a triphasic manner with half-life times of 18 min, 2.6 and 86 h. Within 24 h after the single administration, the excretion of the radioactivity into the urine and feces amounted to 1.3% and 81% of the administered dose, respectively. Tissue radioactivity was higher in the stomach, small intestine, liver, lung, kidney and pancreas, while the radioactivity in other tissues was lower than that in blood. Radioactivity disappeared rapidly from any tissues. In case of repeated administration for 14 d, the disposition of radioactivity was almost same as the result after a single dosing, and radioactivity scarcely remained in any tissues after the last administration.

Administration, Oral

[Metabolic fate of bufalin and cinobufagin].

In the course of study of the metabolic fate of "Kyushin", a traditional medicine containing toad venom, the metabolic fates of bufalin and cinobufagin, main constituents of toad venom, have been studied. Six metabolites were detected in the extracts from incubation mixture of rat liver slice with bufalin, and one main metabolite shown by mass spectroscopy and high performance liquid chromatography (HPLC) to be 3 alpha-bufalin. Serum levels of bufalin and 3 alpha-bufalin were determined by HPLC after oral administration of 2000 micrograms/kg of bufalin, and both compounds appeared in the rat serum. On the other hand, only 3 alpha-bufalin appeared after administration of 20 or 200 micrograms/kg. 3 alpha-Bufalin levels increased dose dependently. Serum levels of cinobufagin and its metabolites and digitoxin were compared after repeated intravenous administration (5 h interval) of cinobufagin or digitoxin. Although digitoxin was accumulated in the rat serum, cinobufagin and its metabolites were not. Inhibitory activities of metabolites of bufalin and cinobufagin on (Na+ + K+)-adenosine triphosphatase were less than those of original compounds.

Administration, Oral

[Pharmacological studies of reiousan which contains bezoar and ginseng: III. Effects on experimental cerebral ischemia].

Pharmacological effects of Reiousan, a crude drug preparation consisting of bezoar and ginseng, on experimental cerebral ischemia and anoxia were studied. After administration of Reiousan, the survival time of mice subjected to hypobaric hypoxia and the gasping duration of isolated rat head tended to increase. Reiousan inhibited all the following: lipid peroxides production in rat brain homogenate, tissue swelling induced by the xanthine-xanthine oxidase system in rat brain cortical slices, rat brain swelling induced by freezing, lipid peroxides production in the rat brain after ligation of bilateral common carotid arteries, and lipid peroxides production in Mongolian gerbil brain after reperfusion following ligation of bilateral common carotid arteries. These effects may result from antioxidant activity of bilirubin, a constituent of bezoar.

Animals

Congestive heart failure model in rabbits: effects of digoxin and a drug containing toad venom.

A low-output-type heart failure model was established in rabbits by protease treatment of the surface of the left ventricular anterior wall. Heart rate, aortic blood flow (AoF), left ventricular pressure (LVP) and maximal rate of rise of LVP (max dP/dt) in this model were maintained at lower levels than in normal rabbits, while left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) were maintained at higher levels, and mean blood pressure (MBP) remained at a normal level. Intraduodenal administration of digoxin and a drug containing toad venom (Kyushin:KY) improved the hemodynamic parameters by increasing the AoF, LVP and max dP/dt and by decreasing the LVEDP and SVR without a significant change in MBP. These results suggest that the beneficial effects of digoxin and KY on this heart failure model originate from their cardiotonic activity.

Amphibian Venoms

Study of regional cerebral blood flow in experimental head injury: changes following cerebral contusion and during spreading depression.

Changes in regional cerebral blood flow (rCBF) following fluid-percussion brain injury (cerebral contusion) were studied in rats using the autoradiographic method. The direct current potential was monitored to identify spreading depression (SD). The rCBF was measured during SD and 2, 4, and 24 hours after injury. rCBF was almost nil in the contused area and decreased considerably in the cortices of the injured side for 4 hours after insult, then recovered by 24 hours. Focal relative rCBF increase occurred in the parietal cortex during SD, and was probably hyperperfusion due to SD. However, the rCBF did not increase over the sham-operated control. The injury probably caused hypoperfusion within 4 hours of insult and abolished the vascular response to SD.

Animals

[Problems of Mason-Likar lead system in treadmill exercise electrocardiography].

A Mason-Likar (M-L) leads system has been widely used in the exercise electrocardiography (ECG) using treadmill for the detection of myocardial ischemia. In routine treadmill exercise ECG using M-L lead, we often observe different patterns of ST-T forms those of II, III and aVF on bipolar leads. In this study, on 213 patients, conventional 12 lead ECG and the M-L lead placement ECG were recorded both at supine and standing positions. A careful analysis was made on all the records of patterns, durations, and amplitudes of QRS and T waves. We also evaluated the ST trendgram of patients with no ischemic changes proven exercise TI-201 myocardial single photon emission tomography (SPECT). Quantitative examination showed no significant differences between those in precordial leads of the standard and the M-L lead system in any subjects. The augmented amplitude of QRS and T waves, the disappearance of abnormal Q-waves in II, III, aVF lead, the negative inversion in QRS phase in lead aVL an left axis deviation were often recognized with M-L lead placement. In treadmill exercise ECG, ST depression more than 1 mm in II, III, aVF lead was noted 14 out of 17 patients with no ischemic changes. The all ST-T changes showed "not-decrescendo" type in ST trendgram. We concluded that rigorous evaluation for electrical axis, the configuration of ST-T waves and the existence of myocardial ischemia in leads II, III, aVF was necessary on treadmill exercise ECG using M-L lead replacement.

Coronary Disease

[Effects of the cortical subarachnoid hemorrhage on cerebral glucose metabolism].

Neurological deficits following human subarachnoid hemorrhage (SAH) have been related to the cerebral arterial spasm and the increase in intracranial pressure (ICP) secondary to the development of hydrocephalus. Metabolic depression in experiment study was thought as resulting from brain stem dysfunction. On the other hand, some reports have shown no relationship between vasospasm and neurological abnormalities. The mechanism of cerebral metabolism depression after SAH remains unclear. The effect of blood in the cortical subarachnoid space on the cerebral metabolism has not been known well. To investigate this effect, a new cortical SAH model was developed using rat and local cerebral glucose utilization (LCGU) after production of SAH was measured. A cortical SAH model: a small burr hole was made on the left parietal bone and the arachnoid membrane was pierced with a tapered glass-needle 60 mu tip in diameter. Fresh autologous non-heparinized arterial blood 0.04 ml was injected into subarachnoid space within 60 seconds through that needle. The blood extended over the left cerebral cortical surface with thin subarachnoid hematoma on the parietal cortex, but did not extend on the right hemisphere and the basal cistern. The increase in ICP during production of SAH was minimal, mean value of 7.2 mmHg and ICP slowly returned to the basal level within 30 minutes. Rats were divided into 3 groups; rats 2 hours (SAH-2h, n = 7) and 48 hours (SAH-48h, n = 7) after production of SAH and rats 2hours after 0.04 ml saline injection for control (Control, n = 7). LCGU was studied according to the methods developed by Sokoloff.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Augmented enkephalin-immunoreactivity in adrenaline-producing phaeochromocytomas.

Immunohistochemical studies for methionine- and leucine-enkephalin were performed on 26 phaeochromocytomas to elucidate the patho-physiological roles of enkephalins. Positive reactions were seen in all phaeochromocytomas with varying intensities. The location of methionine- and leucine-enkephalin agreed fairly well with each other. Stronger immunostaining was obtained in phaeochromocytomas secreting both adrenalin and noradrenaline than in those secreting predominantly noradrenaline. Paroxysmal hypertension was frequently observed in patients with adrenalin-secreting phaeochromocytomas, especially those with marked enkephalin positivity. Urinary excretion of metanephrine was significantly correlated with enkephalin positivity. These findings show that all phaeochromocytomas retain the ability to produce enkephalins of the adreno-medullary or extra-medullary chromaffin tissues from which they derive. Augmented enkephalin-immunoreactivity in adrenalin-producing phaeochromocytomas may be interpreted as reflecting a close association of enkephalins with adrenalin under physiological conditions.

Adrenal Gland Neoplasms

Studies on subtype composition in natural leukocyte interferon preparations.

Antisera raised against partially purified human leukocyte interferon in goat and horse were exhaustively adsorbed and purified. Affinity chromatography using these antibodies gave 10,000-fold purification in one step without losing interferon activity. Then enzyme immunoassay was established with these antibodies and utilized for subtype analysis. Crude and affinity purified leukocyte interferons showed identical profiles of antiviral activity and immunoreactivity when fractionated by means of reversed phase high performance liquid chromatography. These results suggested the possibility of providing mixture of subtypes of leukocyte interferon occurring in natural host response, with comparable purity of recombinant ones.

Animals