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Biomedical subjects

M Miyagawa

Publications and source records attributed to M Miyagawa.

At least 37 records · Page 2Linked to original sources

Experimental assessment of endoscopic mucosectomy with a cap-fitted panendoscope.

BACKGROUND AND STUDY AIMS: The use of a cap-fitted panendoscope is one method of carrying out endoscopic mucosectomy in the esophagus, stomach, and large intestine. The purpose of this study was to determine the optimal volume of physiological saline for submucosal injection, the rate of mucosal extension after saline injection, the initial size of the resected mucosal specimen, and the most appropriate heights for the fitted caps used in the colon and in the rectum, respectively. METHODS: Endoscopic mucosectomies using cap-fitted panendoscopes were carried out on resected surgical specimens from ten patients with colorectal cancer. RESULTS: It was necessary to inject 12 ml of saline under the mucosa to prevent perforation. Submucosal saline injection extended the mucosa by 1.4 +/- 0.2 times. A cap with a height of 7 mm is suitable for performing mucosectomy in the colon safely, while both 7 mm and 10 mm caps can be used in the rectum. The initial size of the resected mucosal specimens obtained with both caps was 12-20 mm (mean 14 mm) in diameter, with no significant differences. As the sizes of resected mucosal specimens reported in the past have been obtained after submucosal saline injection, it appears that larger specimens can be resected with the cap-fitted panendoscope than with conventional methods. CONCLUSIONS: The conditions under which endoscopic mucosectomy using the cap-fitted panendoscope can be performed safely in the colon and the rectum were suggested by this experimental study using resected specimens. A saline injection of 12 ml under the mucosa is necessary to prevent perforation. A cap with a height of 7 mm is the most suitable size for the colon, while both 7 mm and 10 mm caps can be used in the rectum.

Biopsy, Needle↗

Occurrence of toxicity and cell proliferation after a single gavage administration of chloroform to male F344 rats.

Chloroform, an industrial solvent and one of the most common environmental contaminants which produces carcinogenic effects in the liver and kidney of rodents, is not genotoxic in most traditional bacterial and mammalian test systems. Its carcinogenic potential appears attributable to the sustained cell turnover (regenerative hyperplasia) which results from chronic chloroform toxicity. In this present study, cell proliferation (replicative DNA synthesis, RDS) and histopathological changes in hepatocytes and renal tubular epithelial cells were assessed in male F344 rats following a single gavage chloroform exposure (50, 150 or 500 mg/kg). In addition, biochemical parameters (BUN, GOT, LDH and NAG) were examined using plasma and urine samples. Cell proliferation and histopathological changes (e.g. hypertrophy, necrosis, vacuolation) were only seen at the dose of 500 mg/kg in the liver and kidney. At the same dose, all biochemical markers were increased at the 24 to 48 hr time points. These results obtained are thus in line with earlier findings pointing to epigenetic carcinogenicity.

Administration, Oral↗

[Multiple overlapping Wiktor stenting for the treatment of diffuse lesions of small coronary arteries].

This study evaluated the usefulness of multiple overlapping stenting for the treatment of a diffuse lesion in a single and small coronary artery. We studied 48 consecutive patients with a lesion of a vessel with reference diameter < 3.0 mm who received Wiktor stent implants due to suboptimal result or threatened closure after plain old balloon angioplasty (POBA). The patients were divided into 2 groups: Group D, 18 patients with a diffuse lesion with length > or = 15.0 mm who were treated with 2 overlapping Wiktor stents; and Group S, 30 patients with a discrete lesion who were treated with a single Wiktor stent. Two patients with a discrete lesion were not included in Group S because of failure of stenting. Stenting was successful in all patients in Group D. One patient in Group S developed subacute thrombosis after stenting. Follow-up angiography was performed after 6 months. Before treatment, the lesion lengths in Groups D and S were 24.2 +/- 10.0 and 9.2 +/- 4.4 mm, the reference diameters were 2.56 +/- 0.32 and 2.69 +/- 0.33 mm, and the minimal lumen diameters were 0.42 +/- 0.34 and 0.53 +/- 0.40 mm, respectively, with no significant difference in the latter 2 parameters. Restenosis occurred in 72% and 30% (p = 0.01) and revascularization of the target lesion was successful in 67% and in 30% (p = 0.03), in Groups D and S, respectively, both significantly higher in Group D. Follow-up study revealed that the minimal lumen diameter and the net gain were significantly greater in the overlapping portion of the 2 stents than in the proximal and distal portions in Group D, with no significant difference in restenosis rate between these 3 portions. Multiple overlapping stenting using Wiktor stents is useful for diffuse lesions with unfavorable results after POBA even if the affected vessel is smaller than 3.0 mm. However, patients should be carefully observed because restenosis occurs frequently.

Aged↗

Measurement of replicative DNA synthesis (RDS) by a 5-bromo-2'-deoxyuridine (BrdU) labeling technique for detection of hepatocyte proliferation.

The hypothesis has been proposed that cell proliferation, or replicative DNA synthesis (RDS) in S-phase cells, is a nongenotoxic (Ames-negative) mechanism involved in tumorigenesis, providing a very useful conceptual basis for carcinogen testing. In this present study, hepatocyte RDS experiments were conducted using 5-bromo-2'-deoxyuridine (BrdU) labeling in combination with histopathological observation, comparing our results with earlier findings for in situ [3H]thymidine (TdR) labeling. The present BrdU data proved to be consistent with the previous TdR data in all but one case. Hepatocyte RDS induction was observed for some chemicals without hepatotoxicity. BrdU labeling in combination with histopathological observation is therefore a reliable approach to assessment of test compound effects in vivo.

Animals↗

Comparison of adenosine triphosphate and dipyridamole in diagnosis by thallium-201 myocardial scintigraphy.

UNLABELLED: We examined whether 201Tl myocardial scintigraphy with intravenous infusion of adenosine triphosphate (ATP) can be substituted for dipyridamole (DIP) in the diagnosis of coronary artery disease CAD). METHODS: The coronary flow reserve (CFR) during intravenous infusion of ATP (0.10-0.20 mg/kg/min) was compared with that during intravenous infusion of DIP (0.56 mg/kg) using a Doppler flow wire in 19 subjects with normal coronary arteries. The highest CFR level was found in the ATP dose range of 0.16-0.20 mg/kg/min. The CFR at the ATP dose of 0.16 mg/kg/min was significantly higher than that during DIP infusion (4.2 versus 3.6) (p < 0.01), for which reason we adopted this dose of ATP. According, 201Tl SPECT in 140 patients with suspected CAD was performed after infusion of 0.16 mg/kg/min of ATP in 70 of them and 0.56 mg/kg of DIP in the 70 others. RESULTS: ATP stress 201Tl SPECT showed no significant difference in sensitivity and accuracy from DIP stress 201Tl SPECT (87.0% versus 82.9, and 87.1% versus 78.6, respectively). Adverse effects occurred at higher frequency when ATP was used, but they were mild and disappeared rapidly after administration was stopped. CONCLUSION: ATP stress 201Tl SPECT is accurate and safe. The optimal ATP regimen for this purpose is considered to be a 5-min infusion at 0.16 mg/kg/min. However, our data in CAD patients suggest that ATP stress 201Tl SPECT is equivalent to DIP stress 201Tl SPECT in the detection of CAD.

Adenosine Triphosphate↗

Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty.

This protocol was performed to elucidate the preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty (PTCA). A total of 118 patients with 134 vessels undergoing successful PTCA was randomly and prospectively assigned to the probucol group (group P) or the control group (group C). The subjects consisted of 91 men and 27 women, with a mean age of 63.4 +/- 2.3 years. Sixty-six vessels of 59 patients in group P and 68 vessels of 59 patients in group C were evaluated by coronary angiography at 3 months after PTCA. Probucol (0.5 mg/day) was administered between >7 days before PTCA and 3 months after PTCA. The serum total cholesterol (TC) level and the formula low-density lipoprotein cholesterol (formula LDL-C) in group P decreased from 203.8 +/- 43.1 to 169.6 +/- 39.4 mg/dl and from 131.4 +/- 0.7 to 108.7 +/- 2.5 mg/dl, whereas in group C, the levels decreased only from 202.3 +/- 32.1 to 194.2 +/- 29.8 mg/dl and from 129.2 +/- 38.1 to 124.3 +/- 31.7 mg/dl, respectively. The restenosis rate was significantly lower in group P (19.7%; 13 of 66 vessels) than in group C (39.7%; 27 of 68 vessels; p < 0.05). In group P, the probucol blood concentration was significantly higher in the subjects without restenosis (31 +/- 9 microg/ml) than in those with restenosis (18 +/- 8 microg/ml; p < 0.01), but the serum TC and formula LDL-C levels were not significantly different between these two groups. In summary, long-term administration of probucol significantly reduces the incidence of restenosis after PTCA. it was suggested that the mechanism of this preventive effect was not reducing the serum TC or formula LDL-C levels, but rather an inhibitory action on smooth muscle cell proliferation.

Adult↗

[Usefulness of 123I-BMIPP myocardial scintigraphy for evaluation of the left ventricular function in patients with chronic heart failure].

We examined the relationship between free fatty acid metabolism using 123I beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) and cardiac function in patients with chronic heart failure (CHF). Cardiac free fatty acid metabolism was evaluated by the heart to mediastinum ratio (H/M), the heart to lung ratio (H/Lu), the heart to liver ratio (H/Li) and the myocardial uptake ratio (MUR) obtained from the planar imaging. Cardiac function was evaluated by the percent of fractional shortening (%FS) and the amount of left ventricular mass (LV mass) calculated with echocardiography. The study included 34 male and 14 female subjects of CHF with mean age of 61 +/- 9 years; dilated cardiomyopathy (DCM): n = 17, ischemic heart disease (IHD): n = 16, valvular disease: n = 5, hypertrophic cardiomyopathy: n = 4, hypertension: n = 4, amyloidosis: n = 2. The correlations between indices of BMIPP uptake and those of echocardiography were as follows: H/M vs. %FS (r = 0.67, p < 0.01), H/Lu vs. %FS (r = 0.49, p < 0.01), H/Li vs. %FS (r = 0.12, p = 0.42), MUR vs. %FS (r = 0.03, p = 0.86) and MUR/LV mass vs. %FS (r = 0.59, p < 0.01). The correlation coefficient between H/M and MUR/LV mass in patients with IHD was higher than that in patients with DCM. In conclusion, BMIPP, in particular, is a useful tool for evaluating cardiac function in patients with CHF.

Aged↗

Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in diagnosis of coronary artery disease.

OBJECTIVES: The purpose of this study was to evaluate the feasibility, safety and diagnostic accuracy of thallium-201 myocardial tomography with intravenous adenosine triphosphate (ATP) infusion in patients with suspected coronary artery disease. BACKGROUND: Both ATP and adenosine are potent coronary vasodilators with a very short half-life. Several studies have confirmed that the diagnostic accuracy of adenosine thallium-201 scintigraphy is comparable to that with exercise. However, a high incidence of side effects, including atrioventricular (AV) block, has also been reported. Because the appropriate infusion rate for ATP has not yet been determined, this agent has not been tested in combination with myocardial scintigraphy. METHODS: The study group included 253 consecutive patients who underwent thallium-201 myocardial tomography with ATP infusion (0.16 mg/kg body weight per min for 5 min). The occurrence of adverse effects was carefully monitored. Of the 120 patients with coronary angiography, 76 had significant coronary artery disease. Tomographic images were assessed visually and by computer-quantified polar maps, and they were compared with the results of coronary angiography. RESULTS: Although 56% of the patients had some adverse effects, they were transient and mild. In all patients, the ATP infusion protocol could be completed, and no patient required aminophylline; AV block occurred in only 2% of the patients. The sensitivity and specificity were 88% and 80%, respectively, by visual analysis and 91% and 86%, respectively, by computer quantification. CONCLUSIONS: Thallium tomography with ATP is feasible and has a diagnostic value similar to that with adenosine for detecting coronary artery disease. In addition, it may have fewer side effects than adenosine myocardial tomography.

Adenosine Triphosphate↗

Effects of chemical stimulation of the rostral and caudal ventrolateral medulla on cerebral and renal microcirculation in rats.

We investigated the effects of neurons in the rostral and caudal ventrolateral medulla (RVL and CVL) on cerebral and renal microcirculation in rats. Rats were anesthetized with chloralose, paralyzed with tubocurarine, and artificially ventilated. Cerebral and renal blood flows (CBF and RBF) were measured simultaneously using laser-Doppler flowmetry. Chemical stimulation of the RVL neurons by microinjection of the excitatory amino acid L-glutamate increased arterial pressure (AP), whereas that of the CVL neurons decreased AP. Stimulation of the RVL neurons also elicited a stimulus-locked increase in CBF and a decrease in RBF. The percent change in CBF and RBF was dose-dependent as stimulus intensity was increased. Cerebral and renal vascular resistance (CVR and RVR) levels were calculated from changes in CBF or RBF and changes in mean AP. The percent reduction in CVR and percent elevation in RVR were also dose-dependent. Chemical stimulation of the CVL neurons elicited a stimulus-locked decrease in CBF and an increase in RBF. The percent reduction in CBF and percent elevation in CVR were dose-dependent. The percent reduction in RVR was also dose-dependent, while the percent elevation in RBF was not significant. Blood withdrawal reduced AP by a similar degree to CVL stimulation, but did not significantly decrease CBF. The results suggest that RVL and CVL neurons integrate cerebral and systemic microcirculation.

Animals↗

The in vivo-in vitro replicative DNA synthesis (RDS) test with hepatocytes prepared from male B6C3F1 mice as an early prediction assay for putative nongenotoxic (Ames-negative) mouse hepatocarcinogens.

To assess the efficacy of the in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test as a short-term assay, 41 putative nongenotoxic (Ames-negative) mouse hepatocarcinogens, as well as 31 noncarcinogens, were examined using male 8-week-old B6C3F1 mice and an in vitro [methyl-3]thymidine-incorporation technique. Animals were exposed to the maximum tolerated dose (MTD) and 1/2 MTD of each chemical by gavage and after 24, 39 or 48 h, hepatocytes were prepared with a collagenase-perfusion technique. Assessment of the distribution of spontaneous RDS in a total of 337 control mice gave an average incidence of 0.15 +/- 0.08% within the range of 0 to 0.39% (mean +/- 3 x SE) with a 99.7% probability. Values of 0.4% or more for RDS incidences induced by test samples were therefore judged as indicating a positive response in our RDS test. Under the experimental conditions applied, 32 of 41 putative nongenotoxic hepatocarcinogens gave clear positive responses (positive sensitivity: 78%), and of 31 noncarcinogens 25 samples gave negative responses (negative specificity: 81%), thus giving an overall concordance for the RDS test with long-term findings of 79%.

Administration, Oral↗

Acute effects of inhalation exposure to carbon monoxide on schedule-controlled operant behavior and blood carboxyhemoglobin levels in rats.

The acute effects of carbon monoxide (CO) exposure on a steady-state operant behavior (bar-pressing under a VI 60-sec schedule of food reinforcement) were repeatedly measured in (a) rats exposed to various concentrations of CO (500, 1,000, 1,500 and 2,000 ppm) for 1 h and (b) rats exposed to 1,500 ppm for different periods (1, 2 and 4 h). Measurements were made continuously before, during and after the exposure period. Abrupt cessation of the response was produced by exposure to 1,000 ppm or higher concentrations of CO. Recovery from the effects of CO exposure was observed as sudden resumption of responding during the post-exposure period. The duration of exposure required to produce response inhibition was closely correlated with the exposure concentration. The post-exposure interval required for response recovery was also correlated with the exposure concentration. This post-exposure response recovery interval, however, was constant and independent of the duration of exposure when the concentration was fixed at 1,500 ppm. In order to correlate these behavioral changes with an internal index of CO exposure, blood carboxyhemoglobin (HbCO) levels were determined under several exposure conditions corresponding to those of the behavioral observations. It was found that HbCO levels were within a certain range (33-43%) when response recovery occurred, suggesting the existence of a critical HbCO level (threshold) associated with the drastic behavioral change. Hence, these results support the view that blood HbCO is an important determinant of the acute behavioral effects of CO.

Administration, Inhalation↗

Nucleotide sequence of the coat protein coding region of tulip breaking virus.

cDNA of tulip breaking virus-tulip (TBV-tulip) RNA was synthesized and cloned in E. coli. One clone that contains a 4.5 kb insert was identified by restriction enzyme analysis, dot immunobinding assay (DIBA), and partial sequencing. Then 1479 nucleotides of the 3'-terminus of the clone were sequenced and revealed that the sequence contains one open reading frame (ORF), followed by an untranslated region of 255 nucleotides and a poly(A) tract. The deduced amino acid sequence was found to include the C terminus of the predicted RNA-dependent RNA polymerase and the coat protein. A glutamine-alanine dipeptide was identified as a putative NIa protease cleavage site at the N terminus of the coat protein.

Amino Acid Sequence↗

An in vivo-in vitro replicative DNA synthesis (RDS) test using rat hepatocytes as an early prediction assay for nongenotoxic hepatocarcinogens screening of 22 known positives and 25 noncarcinogens.

To evaluate the applicability of an in vivo-in vitro replicative DNA synthesis (RDS) test using rat hepatocytes, we conducted the RDS test with 22 nongenotoxic (Ames-negative) hepatocarcinogens and 25 noncarcinogens under our standardized conditions and judgement criteria. Compared to controls (RDS incidence of under 1.0%), the RDS test gave positive results for 18 hepatocarcinogens (positive sensitivity: 82%), and negative results for 20 noncarcinogens (negative specificity: 80%), and thus the overall concordance was 81%. These findings strongly suggest that the RDS test is an extremely useful method for early detection of nongenotoxic hepatocarcinogens.

Animals↗

Crystallization and preliminary crystallographic data of the alpha-amylase inhibitors, Haim I and Paim I.

Two proteins that act as alpha-amylase inhibitors, Haim I and Paim I, were crystallized and preliminary X-ray diffraction studies on them were carried out. We also sequenced Haim I prepared from Streptomyces griseosporeus YM-25 and confirmed that it is composed of 78 amino acid residues. Crystals of Haim I were grown from ammonium sulfate solution mixed with ethanol by the vapor diffusion technique. The crystals grew as hexagonal bipyramids and diffracted X-rays beyond 2.0 A resolution. They belong to the space group P6(1)22 (or P6(5)22) with unit cell dimensions of a = b = 36.7 A, c = 192.4 A, and contain one molecule per asymmetric unit. Paim I, a protein of 39 amino acid residues produced by Streptomyces corchorusii, was crystallized under similar conditions to Haim I. The crystals diffracted X-rays beyond 2.5 A. They belong to the space group P4(1)2(1)2 (or P4(3)2(1)2) with unit cell dimensions of a = b = 65.4 A, c = 96.1 A, and contain three molecules per asymmetric unit.

Amino Acid Sequence↗

Sebaceous gland carcinoma of the eyelid presenting as a conjunctival papilloma.

A 70-year-old man complained of the sensation of having a foreign body in his left eye in June 1992. A papillary tumor was found growing from the palpebral conjunctiva of the left upper eyelid. On June 30, the conjunctival tumor was excised: the histopathologic findings indicated a malignancy. On August 18, full-thickness excision of the upper eyelid, including the rest of the tumor, was performed. Histopathologic findings showed a well-differentiated sebaceous gland carcinoma. We believe that sebaceous gland carcinoma presenting as conjunctival papilloma, as found in our patient, may be uncommon.

Adenocarcinoma, Sebaceous↗

Behavioral evidence for modified receptor sensitivity in rat brain induced by methyl bromide exposure.

To clarify the neurochemical basis of methyl bromide toxicity in rats, we measured changes in the sensitivity of cerebral monoamine, dopamine (DA) and norepinephrine (NE) receptors, using abnormal behavior and locomotor activity as indicators of receptor sensitivity. Apomorphine and clonidine were used as specific agonists of DA (D1 and D2) and NE (alpha 2) receptors, respectively. In the first experiment, rats were exposed to methyl bromide gas at 25-200 ppm for 8hr once or to methyl bromide at 5-50 ppm 8hr a day for 7 days. The intensity of stereotyped oral (STO) behavior produced by an injection of apomorphine, 0.5 mg/kg i.p., was rated over the following 28 days. The STO behavior of rats exposed to methyl bromide (MB rats) was much more intense than in air-exposed (control) rats. This finding strongly suggests that the sensitivity of striatal DA, D1 and D2, receptors to apomorphine was increased by methyl bromide exposure. In the second experiment, rats were exposed to 50 ppm methyl bromide for 8hr once or to 10-50 ppm methyl bromide 8hr a day for 7 days. Seven days after the final exposure, rats were injected with a small dose of apomorphine, 0.3 mg/kg i.p., and the counts of apomorphine-induced locomotor activity (ALA) were recorded. The ALA counts of MB rats were markedly higher than in the control rats. This finding suggests that the DA receptors in the nucleus accumbens of MB rats are more sensitive to apomorphine than those of control rats. In the third experiment, rats were exposed to 50 ppm methyl bromide, 8hr a day for one day or 7 consecutive days, and the degree of attenuation of locomotor activity following clonidine injection (CLA) was rated. CLA counting was performed 7 days after the final exposure. CLA counts in MB rats were not attenuated as much as in the control rats. This indicates that the cerebral NE receptors, i.e., alpha 2-adrenoceptors, of MB rats may be less sensitive to clonidine than those of control rats. Increased behavioral sensitivity to apomorphine was observed in rats even when exposed to 5 ppm (TLV) methyl bromide.

Animals↗

Neurochemical profile of effects of 28 neurotoxic chemicals on the central nervous system in rats (1). Effects of oral administration on brain contents of biogenic amines and metabolites.

We investigated the effects of oral administration of 28 organic chemical agents, all of which possess neurotoxicity and most of which are used as industrial solvents, on monoamine neurotransmitters and metabolites in the rat brain. Each chemical was administered to rats singly at a dose of one-quarter the LD50 value. Two hours after administration, acetylcholine, 3,4-dihydroxyphenylalanine (DOPA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), serotonin, and 5-hydroxyindoleacetic acid (5HIAA) contents in the small-brain regions were measured. Twenty-one of the 28 chemicals increased acetylcholine in the hippocampus, a ratio (21/28) far higher than the 0.5 expected were these chemicals to have no tendency to increase or decrease acetylcholine. This ratio was calculated for each brain substance. Large differences from 0.5 were also obtained for DOPAC (higher), and for 5HIAA and three neurotransmitters (dopamine, norepinephrine, and serotonin) in the hypothalamus (all lower). The ratios for MHPG and 5HIAA in the medulla oblongata were very high. In the hypothalamus, the concentrations of brain substances were easily altered by the test chemicals, and the turnover rates of hypothalamic norepinephrine and serotonin in the medulla oblongata seemed to be accelerated. Several lines of evidence obtained in previous studies suggest that the increased acetylcholine content in the brain homogenate induced by organic solvents such as toluene may be due to a decrease in acetylcholine release from nerve terminals. Based on the results of the present experiment and previous studies, this acetylcholine suppressing property appears to be common to solvents which possess anesthetic properties.

Administration, Oral↗