Age-related changes in the gastrointestinal tract.
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Aging↗
Biomedical subjects
M Hirata
Publications and source records attributed to M Hirata.
[Evaluation of micro particle enzyme immunoassay (MEIA) for the demonstration of antibody to hepatitis B surface antigen].
A fully automated microparticle enzyme immunoassay (IMx AUSAB, Abbott) has been recently introduced for the detection of the presence of antibody to hepatitis B surface antigen (anti-HBs). The present trial was carried out to determine the feasibility of using the IMx AUSAB with sera and plasma, and for comparison with RIA (AUSAB, Abbott) and EIA (AUSAB EIA, Abbott). According to the kinds of vaccines used and locations of residents, the subjects were divided into six groups. Results obtained were as follows; In the test of 642 sera from 446 vaccines and 196 other inhabitants of Okinawa and Miyazaki prefectures, 388 (87.0%) were found positive for anti-HBs using IMx, 392 (87.9%) with RIA and 359 (80.5%) with EIA. Among those vaccinated with recombinant vaccines, 96.6% were found positive with IMx, 96.2% with RIA and 89.4% with EIA. Among subject vaccinated with plasma derived vaccines, 72.9% were found positive with IMx, 75.7% with RIA, and 68.5% EIA. Quantitative agreement between IMx and RIA among the six groups gave linear correlation coefficients ranging from 0.459 to 0.821. In the group vaccinated with the recombinant vaccine by K company (r = 0.459), anti-HBs was confirmed in many sera by IMx compared to that confirmed by RIA and EIA. In addition, anti-HBs was assayed within one hour by IMx and the procedure was simplified by autoanalyser equipped for this method. The results indicate that the sensitivity of IMx is equal to that of RIA and more than that of EIA, and that quantitative linear correlations were obtained between IMx and RIA, and IMx and EIA.
Hepatitis B Antibodies↗
[Evaluation of micro particle enzyme immunoassay technique (MEIA)-IMx for the detection of antibody to hepatitis A virus].
A new micro particle enzyme immunoassay technique (MEIA, IMx HAVAB, Abbott) has been recently introduced for the detection of antibody to hepatitis A virus (anti-HA). To evaluate the feasibility of the IMx HAVAB, we carried out comparison tests between MEIA, RIA and EIA. Furthermore, we investigated the prevalence of anti-HA in Fukuoka City and Yonaguni Island, Okinawa, Japan using this method. Results obtained were as follows: In the test of 514 sera, 254 (49.0%) were positive by the three methods, and the remaining 260 (50.6%) were negative by the three methods. Examination of diluted sera using IMx revealed that IMx can be used as efficiently as RIA and EIA. Quantitative linear correlations were found between IMx and RIA (r = 0.973), and IMx and EIA (r = 0.969). Anti-HA was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method. On Yonaguni Island, a significant decrease in the overall prevalence of anti-HA from 75.2% in 1980 to 61.1%, in 1990 (p less than 0.05) was found, the prevalence of anti-HA on Yonaguni Island in 1990 was significantly higher than in Fukuoka City (p less than 0.001). These results indicate that the sensitivity of IMx is equivalent to those of RIA and EIA, that it is easier to use than either RIA or EIA and that hepatitis A virus infection in Okinawa, has significantly decreased during the past 10 years, but is still significantly more frequent than in Fukuoka City.
Adolescent↗
A chimeric analog of human and salmon calcitonin eliminates antigenicity and reduces gastrointestinal disturbances.
The minimum region in salmon calcitonin (sCT) which induces antigenicity and gastrointestinal disturbances has been identified by examining the cross-reactivity of several sCT fragments and CT analogs with antisera from sCT-treated patients, and by examining inhibition of gastrointestinal motility of these sCT fragments and CT analogs in conscious dogs. Sixteen residues at the N-terminus of sCT comprised the minimum fragment capable of inducing both activities. Human CT (hCT) showed no antigenicity and a four-order weaker inhibition of gastrointestinal motility than sCT. Based on these data, we synthesized the human and salmon chimeric CT, ACT-15, in which the 16 N-terminal residues were those of hCT and the 16 C-terminal residues were those of sCT. ACT-15 had no cross-reactivity with the antisera and had almost the same weak gastrointestinal inhibition effect as hCT in dog and rat models. Nevertheless, it retained a hypocalcemic activity and an analgesic activity comparable to sCT. These results suggest that the amino acid residues in the N-terminal half of CT are responsible for the formation of antibodies and the induction of gastrointestinal disturbances, but may not influence calcium metabolism or analgesia. Clinical studies of ACT-15 will be needed to confirm this hypothesis.
Amino Acid Sequence↗
Induction of dyspnea by aerosol of endothelin-1/histamine or/methacholine in the conscious guinea pig.
The inhalation of aerosol of endothelin-1 (ET-1) induced dyspneal behavior in conscious guinea pigs pretreated with histamine or methacholine inhalation, although it was not observed by the inhalation of ET-1 alone. The dyspneal response to the inhalation of ET-1/histamine was potently inhibited by indomethacin, but it was not affected by nifedipine or diphenhydramine.
Administration, Inhalation↗
Synthesis and evaluation of iodinated benzamide derivatives as selective and reversible monoamine oxidase B inhibitors.
A new series of iodinated analogues of N-(2-aminoethyl)benzamide was synthesized and evaluated for inhibitory potency and specificity toward monoamine oxidase type-B (MAO-B). Among them, N-(2-aminoethyl)-2-chloro-4-iodobenzamide hydrochloride (2d) showed high inhibitory potency and selectivity against MAO-B. The type of MAO-B inhibition by 2d was non-competitive and the inhibition constant (Ki) was 0.80 microM. Strong and selective in vivo MAO-B inhibition by 2d was also confirmed. The brain MAO-B inhibition by 2d was reversible and the enzyme activity completely returned to the control value 24 h after administration. Compound 2d was, therefore, considered to be a candidate for advanced development as a radioiodinated ligand that may be useful for functional MAO-B studies in the living brain using single photon emission computer tomography.
Animals↗
Formulation optimization of sustained-release tablet of chlorpheniramine maleate by means of extreme vertices design and simultaneous optimization technique.
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Cellulose↗
Role of sympathetic nerve inhibition in the vasodepressor effect of bromocriptine in normotensive and hypertensive rats.
This study aimed to elucidate the mechanism of the hypotensive effect of bromocriptine (BRC), and to investigate whether or not the effects of BRC on the sympathetic nervous system are altered in hypertension. BRC was administered intravenously to normotensive and spontaneously hypertensive rats (SHR). It elicited hypotensive effects dose-dependently in urethane-anaesthetized normotensive rats, an effect which was antagonized with metoclopramide. Pretreatment with intravenous hexamethonium attenuated the hypotensive effect of BRC. BRC decreased plasma norepinephrine (NE) without inhibiting the sympathetic nerve spikes recorded from the postganglionic sympathetic nerve bundle. The hypotensive effect of BRC was significantly greater in SHR than in Wistar Kyoto Rats (WKY). Decrease in NE by BRC was also significantly greater in SHR than in WKY. These results suggest that the hypotensive effect of BRC is induced by suppression of NE release, not by inhibition of sympathetic nerve spikes, and that the dopaminergic presynaptic inhibition is attenuated in SHR.
Animals↗
A quantitative analysis of radiation-induced chromosome aberrations with a fluorescent digital image microscope.
Using a synthetic, alpha satellite consensus DNA unit as a probe, we could show dicentrics as well as acentric fragmented chromosomes in metaphases of gamma-irradiated lymphocyte cells and that the number of appearance of dicentrics or acentric fragments seemed to be proportional to radiation doses. To make such examination with a large number of chromosomes of metaphases, a quantitative fluorescence measurement was performed using a fluorescent microscope digital image analysis system. The relative amounts of fluoresceinated probe hybridized to alpha satellite DNA varied with chromosomes to a certain extent (1-4% of total probe-fluorescence of one metaphase). However, we could score dicentrics and acentric fragments as dots with extraordinarily higher or low percentage in plots of relative amount of probe-fluorescence on metaphase chromosome in gamma-irradiated cells. The number of appearance of acentric fragments were proportional to radiation doses of 1, 2 and 4 Gy. In the case of dicentrics, the number of appearance seemed to be proportional to square doses. Further, to reduce the variation of relative amounts of probe-fluorescence, we tried to make probe-fluorescence reflect the content of alpha satellite DNA on each chromosome more exactly, using a DNA probe amplified by polymerase chain reaction.
Chromosome Aberrations↗
Interactive effects of verapamil and sympathetic nerve stimulation on the sinus and AV nodes in the canine hearts.
The interactive effects of verapamil and sympathetic nerve stimulation on the sinus and atrioventricular (AV) nodes were studied in 33 bilaterally stellectomized and vagotomized dogs. Sinus cycle length (SCL) and AV nodal conduction time (AH) at a constant drive cycle length (600 msec) were recorded. Sympathetic nerve stimulation (SNS) was performed for 40 sec by electrical stimulation of the right stellate ganglion. Several doses of verapamil (0.5-2.0 microgram/ml, 1.0 ml) were injected directly into the sinus and AV node arteries at 20 sec of SNS. In addition, SNS was repeated at two different intensities after verapamil administration. Verapamil significantly increased the SCL and the AH in a dose dependent fashion, which was reduced by SNS. The reductions of SCL and AH by the SNS were attenuated in the presence of verapamil when the stimulation intensity was weak, but not when the stimulation intensity was strong. It is concluded that verapamil and sympathetic nerve activity interact antagonistically on the sinus node automaticity and AV nodal conduction.
Animals↗
[The influence of serum separators on biochemical values in experimental animals].
The influence of three serum separators, A, B and C, on biochemical values was examined. With A or B, changes in the values of ChE, LAP, UN, K, P, Cl and Ca in rat serum; ChE, UN, Cl and Ca in dog serum; and K and P in monkey serum took place over a period of 20 min after blood collection. Therefore, the biochemical values of whole blood were considered to be stable after 20 min. Thus, biochemical tests were conducted on serum from the three serum separators after allowing the blood to stand 20 min. The values obtained for each separator were not markedly different from those of the control. These results suggest that a serum separator is useful for separation of serum of experimental animals under the proper conditions.
Animals↗
[Amounts of urinary metabolites of p-chloroaniline and their half lives in a patient with acute poisoning].
The aim of this study was to elucidate the time courses of amounts of urinary p-chloroaniline (p-CA) metabolites during acute poisoning and to establish a suitable method for biological monitoring of exposure to p-CA. Urinary p-CA metabolites which were previously identified in a patient with acute p-CA poisoning were determined quantitatively over time during admission of a patient by high-performance liquid chromatography (HPLC) and by the colorimetric method of diazo-positive metabolites (DPM). The data of urinary excretion of each p-CA metabolite were fitted to two-compartment model of pharmacokinetics. Major urinary metabolites of p-CA were conjugated p-CA and conjugated 2-amino-5-chlorophenol (2-A-5-CP), and the detected amounts of 2,4-dichloroaniline (2,4-DCA) and free p-CA were small. During the rapid phase for the disappearance of each metabolite, half lives of p-CA, 2-A-5-CP and 2,4-DCA were 2.4, 1.7 and 1.7 h, respectively, and during the slow phase, they were 4.5, 3.3 and 3.8 h, respectively. Urinary p-CA occupied about 62% of the total metabolites detected in the urine, 2-A-5-CP about 36%, and 2,4-DCA about 1%. 2-A-5-CP and p-CA were detected in the urine of the patient obtained on days 3 and 4, respectively, after the poisoning, but the amount of DPM after the second day of the poisoning was in the range of that of non-exposed persons.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
[Excretion of p-chloroaniline metabolites into urine. Excretion of 2,4-dichloroaniline and p-chloroformanilide].
Previously, we identified by gas chromatography/mass spectrometry (GC/MS) urinary metabolites of p-chloroaniline (p-CA) in a patient with acute p-CA poisoning. Among these metabolites there is a possibility that 2,4-dichloroaniline (2,4-DCA) and p-chloroformanilide (p-CFA) are produced through some unknown metabolic pathways in human. In order to clarify whether 2,4-DCA and p-CFA were produced within the human body or not, an attempt was made to detect these metabolites in the patient's urine samples prepared by various pretreatments, using both GC/MS and high performance liquid chromatograph. In addition, the detection of these metabolites in non-exposed person's urine samples spiked with p-CA and 2-amino-5-chlorophenol was attempted by GC/MS using same the procedures in order to examine whether p-CA and 2-amino-5-chlorophenol excreted as metabolites were further changed to 2,4-DCA or p-CFA in the urine or not. 2,4-DCA was found abundantly in the ethereal extracts from the patient's urine samples hydrolyzed with hydrochloric, sulfuric and nitric acids, but only small amounts from intact urine samples by GC/MS. No 2,4-DCA was detected in the urine samples to which were added p-CA and 2-amino-5-chlorophenol. p-CFA was found in the ethereal samples which were extracted at acidic conditions from the patient's urine samples by GC/MS at the injection port temperature of 250 degrees C of the gas chromatograph, but the p-CFA peak disappeared at the injection port temperature of 150 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Aniline Compounds↗
Morphological study of parafollicular cells and the parathyroid gland in the house shrew (Suncus murinus).
A morphological study of parafollicular cells in the thyroid gland and parathyroid gland of the house shrew (Suncus murinus) was made. The results indicated that (1) there were two pairs of parathyroid glands which were located in the upper part of the house shrew thyroid gland, (2) the volumes of the house shrew parathyroid glands ranged from 0.014 to 0.079 mm3, (3) the number of parafollicular cells along the follicles was largest in the upper part of the thyroid lobe, while no parafollicular cells were present in the isthmus, and (4) there were about 20 parafollicular cells per 100 follicular cells and 1.519 parafollicular cells per follicle. The number of parafollicular cells per 100 follicular cells was thus about 5 times larger than that in rats and the number of parafollicular cells per follicle about 2.5 times larger than that in rats.
Animals↗
Stereoselective conjugation of a uricosuric diuretic with glutathione by glutathione transferase 3-3.
1. The activity of glutathione (GSH) transferases in rat liver cytosol was inhibited by the (-) enantiomer of a uricosuric diuretic (6,7-dichloro-5[N,N-dimethylsulphamoyl]-2,3-dihydrobenzofuran-2-ca rboxylic acid, DBCA) in a concentration-dependent manner. Although the DBCA (+) enantiomer inhibited the activity of liver cytosol GSH transferases, it was less effective. 2. Among four purified GSH transferase isozymes obtained from rat liver cytosol, isozyme 3-3 showed stereoselective interactions with the enantiomers of DBCA. This isozyme most actively and preferentially catalysed the transfer of GSH to DBCA (-) enantiomer.
Animals↗
Purification and molecular properties of 2-carboxybenzaldehyde (CBA) reductase from phenobarbital-treated rat liver.
1. A rat liver cytosol enzyme, tentatively named CBA reductase, catalyses the conversion of 2-carboxybenzaldehyde (CBA) to 2-hydroxymethyl benzoic acid in the presence of NADH (or NADPH). CBA reductase is useful for exploring the mechanism of in vitro enzyme induction, as the enzyme can be induced by phenobarbital (PB) both in vivo and in vitro. 2. Possible involvement of glutathione (GSH) in gene expression was suggested by a recent study with cultured rat hepatocytes. 3. CBA reductase was purified about 200-fold by a combination of column chromatography and isoelectric focusing in the presence of mercaptoethanol. 4. The ability to form 2-hydroxymethyl benzoic acid was lost when the enzyme was chromatographed on a hydroxylapatite column in the absence of mercaptoethanol; however, it was restored if sulphydryl compounds or bovine serum albumin was added to the eluate from the column. 5. Gel filtration showed the molecular sizes of CBA reductase from the 105,000g supernatant fraction of rat liver extracts and the purified preparation were 64 kDa and 49 kDa, respectively. 6. The results suggest that sulphydryl substances and some proteins play important roles in preserving the molecular and catalytic properties of CBA reductase.
Alcohol Oxidoreductases↗
Calcium suppresses central angiotensin II pressor response less in SHR.
To determine whether calcium alters central cardiovascular regulation, cardiovascular responses to intracerebroventricular (ICV) injection of calcium were recorded in conscious Wistar rats. Calcium injection consistently produced dose-dependent decreases in mean parterial pressure and heart rate. Pretreatment with a calcium channel blocker, diltiazem, attenuated cardiovascular responses to calcium. Decreases in plasma norepinephrine indicated the contribution of sympatho-inhibition to vasodepression by calcium. Preceding calcium injection reduced pressor responses to ICV-injected angiotensin II. These findings suggest that there is a pharmacological interaction between calcium and angiotensin II in the central nervous system. In spontaneously hypertensive rats (SHR), cardiovascular responses to calcium was larger than Wistar Kyoto rats (WKY). By contrast, calcium reduced pressor responses to angiotensin II only in WKY but not in SHR. Because the central interaction between calcium and angiotensin II has been different in SHR, our results imply that this difference may be related to the maintenance of high blood pressure in SHR.
Angiotensin II↗
[Guanidino compounds in the elderly].
To examine the metabolism of guanidino compounds in the elderly, we measured the serum concentrations of urea nitrogen, creatinine (Cr), guanidinoacetic acid (GAA) and creatine (CR) in middle-aged and elderly subjects. We also measured muscle mass in the elderly. The elderly subjects tended to have lower serum GAA concentrations than middle-aged subjects. On the contrary, CR concentrations of elderly subjects were higher than those of middle-aged subjects. Bedridden elderly subjects tended to have lower serum GAA concentrations and lighter muscle mass than ambulatory elderly subjects. On the contrary, serum CR concentrations of bedridden subjects were higher than those of ambulatory subjects. CR is an essential substance for muscle energy metabolism. These results indicate that high serum CR concentrations due to low CR metabolism in skeletal muscle might suppress glycine amidinotransferase (GAT) activity, resulting in decreased GAA production in the elderly.
Aged↗