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Biomedical subjects

A Sekine

Publications and source records attributed to A Sekine.

At least 37 records · Page 2Linked to original sources

Nonsteroidal anti-inflammatory drug-associated colitis with a histology of collagenous colitis.

Here we report a case of nonsteroidal anti-inflammatory drug (NSAID)-associated colitis with a histology of collagenous colitis in a 77-year-old woman. The patient had taken aspirin since 1993 after being diagnosed at another hospital, as having multiple cerebral infarctions. She began to suffer from intermittent diarrhea in April 1999. Serological examination showed hypoproteinemia, which indicated that she had protein-losing enteropathy. By July 1999, she had undergone colonoscopic examination four times. Biopsy specimens taken during the fourth colonoscopy revealed collagenous colitis. As the patient had been taking aspirin for 6 years, she was diagnosed as having NSAID-associated colitis with a histology of collagenous colitis. When she stopped taking aspirin, the diarrhea ceased. Three months later, the patient underwent a fifth colonoscopy. A histological examination of the biopsy specimen revealed that the collagen band had vanished. NSAID-associated colitis sometimes shows collagenous colitis histologically and is cured by withdrawing the drug. It is important to differentiate NSAID-associated colitis, even if it shows a histology of collagenous colitis, from collagenous colitis as the two diseases differ in etiology and therapy.

Aged↗

Expression of a zinc-binding domain of boar spermatidal transition protein 2 in Escherichia coli.

Transition protein 2 (TP2; 137 amino acid residues) from boar late spermatid nuclei has three potential zinc finger motifs in the N-terminal 34 region. Gel shift assays revealed that boar TP2 recognized a CpG island sequence in a zinc-dependent manner. However, there was some nonspecific recognition of the oligonucleotide. Then, we constructed the expression system of zinc-binding domain of TP2 (TP2Z) (residues 1-103) in Escherichia coli. Double-stranded DNA fragments encoding TP2Z were synthesized as 18 fragments with 103 residues, annealed, and cloned into the expression plasmid pET11d. TP2Z was expressed upon induction with 1 mM isopropylthiogalactoside and extracted with acid including 0.71 M 2-mercaptoethanol. TP2Z was purified by ion-exchange chromatography on Fractogel EMD SO(-)(3) and HPLC on Nucleosil 300 7C18 and on Diol-120. Atomic absorption and CD spectroscopy showed that TP2Z bound three atoms of zinc per molecule of the protein and underwent a zinc-dependent conformational change in a manner similar to that for intact TP2. Gel shift assays indicated that TP2Z recognized a CpG island sequence more specifically than intact TP2 and that the specificity is dependent on zinc.

Amino Acid Sequence↗

Effects of diadenosine tetraphosphate on systemic and regional hemodynamics in dogs.

PURPOSE: Diadenosine tetraphosphate (AP(4)A) produces vasodilation and hypotension. If AP(4)A is to be employed clinically, its influence on systemic and regional hemodynamics needs to be investigated. In this study, we observed systemic and regional hemodynamics during reduction of mean arterial pressure (MAP) induced by AP(4)A in dogs. METHODS: Nineteen mongrel dogs were allocated to three groups: those given physiological saline (vehicle group) and dogs in which MAP was decreased either by 8% (8% group) or by 30% (30% group) by infusion of AP(4)A. Systemic hemodynamics and microsphere-determined regional blood flow to vital organs were assessed before and during AP(4)A infusion. RESULTS: In the 8% group, cardiac output (CO) increased, and systemic vascular resistance (SVR) decreased during AP(4)A infusion. Although regional blood flow to myocardium and portal organs increased, hepatic blood flow decreased. In the 30% group, heart rate and SVR decreased, and stroke volume index increased without change in CO. Regional blood flow to myocardium, kidneys, and portal organs increased. In both groups, cerebral blood flow remained unchanged. CONCLUSION: During the decrease in MAP induced by AP(4)A, there were increases in regional blood flow distributed to the myocardium, kidneys, and portal organs, without change in the blood supply to the brain. This finding suggests that AP(4)A may be clinically useful for reducing blood pressure without compromising blood flow to vital organs.

Journal Article↗

A negative component on event related potential recorded in the drowsy state.

Behavior of event related potential (ERP) components in the drowsy state was examined in nine subjects using oddball paradigm. A component with peak latency of 300 msec, N300, was superimposed on ERP in the drowsy state. N300 appeared also in stage 1 of NREM sleep and closely resembled vertex sharp wave evoked by sound stimulation in both scalp distribution and peak latency. It was suggested that N300 recorded in the drowsy state and vertex sharp wave recorded in stage 1 of NREM sleep are generated by the identical synchronizing mechanism in the brain.

Adult↗

Cortical activity of REM sleep often occurs earlier than other physiological phenomena.

N300 appearing in response to sound stimulus was used as an index to determine the occurrence of cortical activity characterizing REM sleep. In 5/10 subjects, marked reduction of N300 amplitude occurred even in the period of 0.5-2.5 min immediately preceding the appearance of muscle atonia characterizing REM sleep. Neither muscle atonia nor rapid eye movements appeared prior to the marked reduction of N300 amplitude in any subject. This suggests that the cortical activity characterizing REM sleep sometimes occurs a few minutes (or less) earlier than other physiological phenomena.

Adult↗

A novel histamine 2(H2) receptor antagonist with gastroprotective activity. I. Synthesis and pharmacological evaluation of N-phenoxypropylacetamide derivatives with thioether function.

In an attempt to develop new types of anti-ulcer agents, a series of N-(phenoxypropyl)acetamide derivatives with a thioether moiety and their sulfur-oxidized analogues were synthesized and evaluated for histamine H2-receptor antagonistic activity, Ca antagonistic activity and gastric anti-secretory activity in the lumen-perfuseed rat. Selected compounds were also tested for gastroprotective activity, which was expected to be based on Ca antagonistic activity. Structure-activity relationships are discussed. As a thioether moiety, -CH2-S(O)p-CH2-Ar (Ar; phenyl or furyl) was found to be optimal for the above activities. Especially, N-[3-[(3-(piperidinomethyl) phenoxy]propyl]acetamide with a benzyl sulfinyl, benzylsulfonyl, furfurylsulfinyl or furfurylsulfonyl group showed potent gastroprotective activity upon oral administration in a rat model. These compounds are candidates for novel anti-ulcer drugs with gastric anti-secretory and gastroprotective activities. 2-Furfurylsulfinyl-N-[3-[(piperidinomethyl)phenoxy]propyl]ac etamide was the most potent among the compounds tested and was given the code designation FRG-8701.

Acetamides↗

A novel histamine 2(H2) receptor antagonist with gastroprotective activity. II. Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings.

We recently found that N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide derivatives with a thioether function showed gastric anti-secretory and gastroprotective activities and that the thioether function (particularly furfurylthio or furfurylsulfinyl) was essential for gastroprotection. In the present study, a series of 2-furfurylthio and 2-furfurylsulfinyl acetamide derivatives were synthesized and evaluated for histamine H2 receptor antagonistic activity, gastric anti-secretory activity and gastroprotective action. Based on the structure of N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide, we designed compounds, in which the 3-(piperidinomethyl)phenoxy part is substituted with many types of heteroaromatic ring attached to the tertiary amine and the propyl group is replaced with other carbon linkages. Structure-activity relationships are discussed. 2-Furfurylsulfinyl-N-[4-[4-(piperidinomethyl)-2-pyridylox y]- (Z)-2-butenyl]acetamide was the most potent among the tested compounds and was given the code designation FRG-8813.

Acetamides↗

Marked suppression of cortical auditory evoked response shortly before the onset of REM sleep.

In 10 of 12 subjects examined, the amplitude of N300, a component of the cortical auditory evoked potential, was evidently smaller in rapid eye movement (REM) sleep than in non-REM sleep. The start of the reduction associated with the onset of the first episode of REM sleep was examined in these 10 subjects. In five of these, a marked reduction of N300 amplitude occurred 0.5-2.5 min before the appearance of muscle atonia of REM sleep. In two subjects, a similarly marked reduction of the N300 amplitude occurred 0.5-1.0 min before the disappearance of sleep spindles or K-complexes. This suggests that a suppression of the synchronizing mechanism in the cerebrum sometimes occurs briefly prior to the occurrence of other physiological phenomena associated with REM sleep.

Acoustic Stimulation↗

Coronary effects of diadenosine tetraphosphate resemble those of adenosine in anesthetized pigs: involvement of ATP-sensitive potassium channels.

Diadenosine tetraphosphate (Ap4A) is an adenine nucleotide with vasodilatory properties. We examined the effects of Ap4A on coronary circulation in comparison with those of adenosine, its metabolite, in anesthetized pigs. Left atrial (LA) infusion of Ap4A at increasing doses of 100, 200, and 300 micrograms/kg/min increased coronary blood flow (CBF) and decreased systemic blood pressure (BP) and coronary vascular resistance (CVR). Ap4A had no effect on large epicardial coronary artery diameter (CoD). Likewise, LA infusion of adenosine at doses of 150 and 300 micrograms/kg/min increased CBF and decreased BP and coronary vascular resistance (CVR) but did not affect CoD. Therefore, the vasodilatory effects of Ap4A and adenosine were predominant in small coronary resistance vessels and negligible in large coronary arteries. Pretreatment with glibenclamide (2 mg/kg, intravenously, i.v.), a specific blocker of ATP-sensitive potassium channels (KATP), attenuated alterations of CBF, BP, and CVR induced by Ap4A and by adenosine. In contrast, treatment with cromakalim (0.5 microgram/kg/min i.v.), an activator of KATP, enhanced the coronary effects of Ap4A and adenosine. Therefore, the opening of KATP in the pig coronary circulation is involved in the in vivo vasodilatory effects of Ap4A and adenosine. Treatment with 8-phenyltheophylline (8-PT, 4 mg/kg i.v.), an adenosine receptor antagonist, suppressed CBF increases induced by Ap4A (20 micrograms/kg/min, intracoronarily, i.c.) and adenosine (5 micrograms/kg/min i.c.) by 68 and 90%, respectively. These findings suggest that the in vivo coronary effects of Ap4A are largely caused by the opening of KATP through rapid degradation to adenosine to activate adenosine receptors.

Adenosine↗

K-complex evoked in NREM sleep is accompanied by a slow negative potential related to cognitive process.

Evoked cortical responses to two kinds of auditory stimuli (rare and frequent) were analyzed to determine whether or not a K-complex evoked in stage 2 of NREM sleep is accompanied by some endogenous cognitive components of the event-related potential. All the 7 subjects examined in this sleep state failed to provide the correct behavioral response to auditory stimuli, but a K-complex was evoked more frequently by rare stimuli than by frequent stimuli. EEG segments in stage 2 were averaged separately according to the presence or absence of K-complexes emerging just after the stimulation. In cases where K-complexes did not emerge, a long-lasting negative potential of relatively low voltage appeared in the difference wave, which was obtained by subtracting the averaged EEG for frequent stimuli from that for rare stimuli. In cases where K-complexes emerged, a similar long-lasting negative potential of large amplitude appeared in the difference wave. These data may indicate that a K-complex evoked by an external stimulus is accompanied by a potential related to a cognitive process, which appears with greater amplitude in cases where a K-complex is evoked.

Acoustic Stimulation↗

Intravenous diadenosine tetraphosphate in dogs. Cardiovascular effects and influence on blood gases.

Diadenosine tetraphosphate (AP4A) has a considerable vasodilating effect. Its dose was adjusted to decrease mean arterial pressure (MAP) by 20%, 40%, 50%, 60%, and 80% of the pretreatment value, and the effects on hemodynamics and gas exchange were evaluated. AP4A produced a dose-dependent decrease in MAP within the range of doses which decreased blood pressure by up to 60%. Heart rate remained constant at hypotension levels of 40% or less, but decreased significantly at hypotension levels of 50% or more. Cardiac output increased significantly at hypotension levels of 40% or less. Systemic vascular resistance (SVR) showed a significant decrease at that time. No significant changes were observed in central venous pressure and pulmonary capillary wedge pressure at any level of hypotension. Arterial oxygen tension and calculated pulmonary shunt ratio showed no change. Base excess and pH were decreased significantly with a 60% or 80% fall of blood pressure. In conclusion, AP4A seems to act on the resistance vessels and cause a decrease in SVR.

Acid-Base Imbalance↗

Effects of hypoxia on stimulus-release coupling mechanisms in cultured bovine adrenal chromaffin cells.

To clarify the effects of hypoxia on stimulus-release coupling, we have examined the effects of hypoxia on nicotine-induced catecholamine (noradrenaline and adrenaline) release from, and 22Na+ influx, 45Ca2+ influx and cytosolic free Ca2+ concentration ([Ca2+]i) in, cultured bovine adrenal chromaffin cells. Experiments were carried out in media pre-equilibrated with 21% O2/79% N2 (control) or with 0% O2/100% N2 (hypoxia). Cells were stimulated with either nicotine (activating nicotinic acetylcholine (ACh) receptors) or a high K+ concentration (55 mmol/l KCl; directly activating voltage-dependent Ca2+ channels). Hypoxia reduced both nicotine- and high K(+)-induced catecholamine releases from the cells, but the reduction of the former (to about 30% of the control value) was more pronounced than that of the latter (to about 40% of the control value). Nicotine-induced 22Na+ influx, which is considered to reflect the function of nicotinic ACh receptors, was inhibited by hypoxia. Both nicotine- and high K(+)-induced 45Ca2+ influx into the cells were reduced by hypoxia, but the reduction of the former was more pronounced than that of the latter. Nicotine- and high K(+)-induced increases in [Ca2+]i were reduced by hypoxia to about 30% and 40% of the control values, respectively. These results suggest that hypoxia reduces cation influxes (Na+ and Ca2+) through both the ligand-gated cation channels of the nicotinic ACh receptor and the voltage-dependent Ca2+ channels.

Animals↗

Axial eye-length measurement by wavelength-shift interferometry.

A simplified noncontact measuring technique for axial eye length was developed. According to this method, the wavelength shift of a single-mode laser-diode beam that is irradiated onto the eyeball causes a phase shift in the interference fringes of reflections from the retina and the cornea. Then the optical distance between the cornea and the retina is obtained from the phase-shift measurement. High-speed axial eye-length measurements can be performed by using a laser diode on a pulse-modulation drive and signals from the reference light path as an analog-to-digital-conversion trigger. Compared with the technique that uses partially coherent light, this technique is inferior in terms of measurement accuracy but superior in its wide, measurable range of 16-32 mm. The results of measurements of 21 adults showed that 2 standard deviations of measurement was 2 sigma = +/- 0.11 mm.

Adult↗

Purification of GTPase-activating protein specific for the rho gene products.

A GTPase-activating protein specific for the rho gene products (rho-GAP) was purified from the cytosol of bovine adrenal gland. Purification procedures consisted of ammonium sulfate fractionation, chromatographies on columns of phenyl-Sepharose and CM-Sepharose, gel filtration on a TSK-gel G3000SW, and Mono S fast protein liquid chromatography. By these procedures the activity was purified about 36,000-fold with a recovery of 0.6%. The final preparation showed a major protein band at Mr 28,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stimulated GTP hydrolysis by the purified rho A protein in a time- and dose-dependent manner. No stimulation was found for ras p21. The ADP-ribosylation on the rho protein by botulinum C3 exoenzyme did not affect its interaction with the purified rho-GAP.

Adenosine Diphosphate Ribose↗