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Biomedical subjects

Y Okazaki

Publications and source records attributed to Y Okazaki.

At least 217 records · Page 12Linked to original sources
PubMed1994

Nephrotoxicity induced by adenine and its analogs: relationship between structure and renal injury.

Twenty-four adenine analogs were administered to mice and the relationship between the structure of analogs and the occurrence of renal injury was examined. Plasma urea nitrogen (UN) and creatinine levels were measured 24 h after oral administration of analogs. Both levels increased in the adenine-, 8-azaadenine-, isoguanine-, or 6-dimethyl aminopurine (6-DMAP)-administered group, but did not increase in the other analog groups. From light microscopy, the damages of tubuli, mainly of proximal tubuli, were observed in the kidneys of these four groups. The common property of these compounds is the strong basicity of nitrogen which binds the 6-position of the purine ring. Furthermore, UN and creatinine increased time-dependently with intravenous administration of isoguanine. When adenine was intravenously administered, UN slightly increased at 1 h, but creatinine was unchanged. No changes were observed in the 6-DMAP- or 8-azaadenine-administered group. The basicity of nitrogen which binds to the 6-position of the purine ring is thus considered to be related to the occurrence of renal injury with oral administration, and isoguanine has high affinity with the kidney.

Adenine↗
PubMed1994

Nephrotoxicity induced by a single dose of adenine: effects of 4-aminopyrazolo[3,4-d]pyrimidine and allopurinol.

The effects of allopurinol and 4-aminopyrazolo[3,4-d]pyrimidine (4APP) on adenine-induced renal injury in mice were examined. Plasma urea nitrogen (UN) and creatinine levels increased after the oral administration of adenine to mice. However, plasma UN and creatinine levels decreased inversely with the dose of 4APP when a different dosage of 4APP was administered together with adenine. Yet 4APP did not have any effect on the UN or creatinine levels when 4APP was administered after adenine administration. Plasma UN and creatinine levels increased in the allopurinol-administered group as in the adenine-administered group. Moreover, from light microscopic observation by hematoxylin-eosin staining, microvacuolic changes in the proximal tubuli were detected in the mouse kidney in the adenine-administered group, and epithelial cell loss, degeneration and microvacuolic changes in the proximal tubuli were observed in the mouse kidney in the adenine-and-allopurinol-administered group. However, there were no changes in the proximal tubuli in the mouse kidney in the adenine-and-4APP-administered group. These findings suggested that 4APP inhibits the action of adenine in the mouse kidney.

Adenine↗
PubMed1994

Amino acid sequence of a porcine zona pellucida glycoprotein ZP4 determined by peptide mapping and cDNA cloning.

Mammalian zona pellucida is an attractive target for developing a contraceptive vaccine. In this study, the amino acid sequence of a core protein of porcine zona pellucida glycoprotein ZP4 was determined by peptide mapping and cDNA cloning. Two kinds of ZP4 peptides were identified: one consisted of 128 amino acid residues and the other of 133 amino acid residues with an additional five amino acid sequence at the carboxy-terminal end of the 128 amino acid peptide. Both peptides had two potential N-linked glycosylation sites. The 128 amino acid peptide showed 39.1% similarity to the amino-terminal region of mouse ZP2 polypeptide. The positions of five cysteine residues were the same for porcine ZP4 and mouse ZP2. The cloned cDNA possessed an additional 195 nucleotides at the 3' end of the sequence corresponding to the 133 amino acid peptide. This additional sequence was found to encode the amino-terminal 10 amino acid sequence of porcine ZP2 polypeptide. These results suggest that porcine ZP4 and ZP2 are derived from a common parent polypeptide by proteolytic cleavage at the position between 133 and 134 residues.

Amino Acid Sequence↗
PubMed1994

Gradient of mineral contents of vertebral column with special reference to intervertebral discs.

To study quantitatively the mineral elements in the vertebral column, we examined the vertebrae and intervertebral discs resected from three normal cadavers which died at middle age, by inductively coupled plasma atomic emission spectrometry. The relative contents of calcium, phosphorus, and sodium in vertebrae were high in the order from cervical to lumbar vertebrae. The ratios of calcium per phosphorus were 1.80 +/- 0.25 in cervical vertebrae, 1.59 +/- 0.22 in thoracic vertebrae, and 1.23 +/- 0.24 in lumbar vertebrae. The ratio of cervical vertebrae was the highest among them. In regard to intervertebral discs, both the relative contents of calcium and phosphorus were very much higher in the intervertebral discs between the 4th and 8th thoracic vertebrae than the others.

Bone Density↗
PubMed1994

[Traumatic transection of the descending thoracic aorta--2 successful case reports].

We report two cases of acute traumatic transection of the descending thoracic aorta that were successfully treated. Case 1 (a 24-year-old male) was admitted to our hospital because of unconsciousness with multiple severe injuries including pelvic fracture, hepatic laceration, brain contusion, and multiple fractures in the extremities. An emergency operation was performed to control the active bleeding from the hepatic laceration and the transluminal arterial embolisation of the internal iliac arteries for the pelvic fractures. Since the condition of the patient was very serious, we had to wait the repairment of the thoracic aorta for 3 weeks. The operation was successful using extracorporeal circulation. Case 2 (a 22-year-old female) suffered traumatic transection of the descending thoracic aorta without other injuries and received an emergency operation, which was successful. The strategy for the treatment of an aortic transection is difficult, especially when involving multiple injuries. However provided the decision to operate takes careful account of the general condition of the patient, then a successful result might be obtained even in a very severe case.

Adult↗
PubMed1994

Split dose iodine-123-IMP SPECT: sequential quantitative regional cerebral blood flow change with pharmacological intervention.

UNLABELLED: At least two quantitative rCBF measurements are needed to evaluate rCBF changes with pharmacological intervention. We have developed the split dose 123I-IMP SPECT method, which enables measurement of rCBF to be repeated in a short time. METHODS: Thirty-one cerebrovascular disease patients were investigated to assess reproducibility and vasoreactivity to acetazolamide. During 44-min dynamic SPECT imaging, 123I-IMP injection and respective arterial sampling were performed twice at an interval of about 25 min. The rCBF values were calculated using a microsphere model in which the washout of 123I-IMP from the brain can be negligible in the first several minutes after injection. For the second rCBF measurement, the remaining activity due to the first 123I-IMP injection was estimated and subtracted from the total brain activity. RESULTS: In ten patients, two consecutive resting mean rCBF values in the MCA territory (CBF1 and CBF2) had good correlation (CBF1 = 47.4 +/- 4.0 (ml/min/100 ml: mean +/- s.d.), CBF2 = 45.2 +/- 8.2, CBF2 = 0.900*CBF1 + 2.9, r = 0.915). In 11 patients with occlusive lesions in the unilateral ICA system, mean rCBF in the MCA territory was increased by only 27.7% +/- 14.0% in the affected side by a 1-g intravenous acetazolamide injection, while 44.5% +/- 12.3% increase was found in the nonaffected side. In 10 patients without a major arterial lesion, a 49.7% +/- 17.0% increase of rCBF was demonstrated. CONCLUSIONS: This split dose method 123I-IMP SPECT can be useful to estimate vascular reserve.

Acetazolamide↗
PubMed1994

[A successful case report of coronary artery bypass grafting under ventricular fibrillation with circulatory arrest].

Coronary artery bypass grafting in a 78-year-old female with severely calcified ascending aorta was performed successfully. Bilateral internal thoracic arteries and saphenous vein were anastomosed under ventricular fibrillation and hypothermia without aortic cross-clamping. Proxymal anastomosis of saphenous vein graft was performed directly under circulatory arrest in a normal part of ascending aorta which was confirmed by intraoperative ultrasonography. Weaning from ECC was easy and no neurological complication was observed after operation. Bypass grafts were patent on postoperative coronary angiogram and postoperative course was uneventful. We think the technique of circulatory arrest and intraoperative ultrasonography were useful in a patient with severely calcified ascending aorta.

Aged↗
PubMed1994

Anti-atherosclerotic and plasma lipid lowering effects of the novel calcium blocker with alpha 1-adrenoceptor antagonistic activity, monatepil, in high cholesterol diet-fed Japanese Macaca fuscata monkeys.

1. The preventive effects of atherosclerosis and hyperlipidemia of monatepil ([(+-)-N-(6,11-dihydrodibenzo [b,e]thiepin-11-yl)-4-(4-fluorophenyl)-1-piperazine-butanamide+ + +]monomaleate , AJ-2615, CAS 103377-41-9), a new antihypertensive drug with potent calcium antagonistic and alpha 1-adrenoceptor blocking activities, were investigated in Japanese monkeys (Macaca fuscata) fed with a cholesterol-rich diet (2% cholesterol + 6% corn oil) and compared with those of prazosin. 2. The dose of monatepil selected (30 mg/kg/d, p.o., 6 months) was the plasma concentration dose level of antihypertensive therapy and that of prazosin (2 mg/kg twice daily, p.o., 6 months) was the dose where hypolipidemic effect in cholesterol-fed monkeys has been reported. 3. In the cholesterol diet control group (n = 7), plasma levels of total cholesterol and low-density lipoprotein (LDL) significantly increased and that of high-density lipoprotein-cholesterol (HDL-C) decreased compared with the normal diet group (n = 5). In the monatepil group (n = 5), these changes were significantly suppressed. In the prazosin group (n = 5), these changes were also inhibited but the inhibitory effect was weaker than in the monatepil group. 4. The cholesterol content and sudanophilic area in the aorta indicating atheromatous lesions in the cholesterol-diet fed control group were significantly higher than those in the normal diet control group. In the monatepil group, these changes were significantly suppressed whereas in the prazosin group these changes were partially inhibited. 5. In the histological study, aortic lesions characterized by aggregations of foam cells were observed in the cholesterol-diet control group, while there was little change in the monatepil group. The anti-atherogenic effect of prazosin was weaker than that of monatepil. 6. Coronary atheromatous lesions were found in 4 out of the 7 animals in the cholesterol-diet control group and 3 out of the 5 animals in prazosin group. In contrast, no coronary atheromatous lesion was found in the monatepil group. 7. The treatment with monatepil did not influence food consumption, body weight, physical signs or blood biochemistry. 8. The anti-atherosclerotic and plasma lipid-lowering effects of monatepil may in part be attributable to its calcium antagonistic, alpha 1-adrenoceptor blocking, and anti-lipid peroxidation activities. 9. In conclusion, monatepil is a new class of antihypertensive agent that possesses anti-atherogenic properties and the ability to reduce plasma lipid levels, a main risk factor for atherosclerosis.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Carbon dioxide reactivity by consecutive technetium-99m-HMPAO SPECT in patients with a chronically obstructed major cerebral artery.

UNLABELLED: In the management of major cerebral artery obstruction, cerebral perfusion reserve is key to introducing cerebral revascularization surgery. The purpose of this study was to evaluate the feasibility of assessing cerebral perfusion reserve by consecutive 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) SPECT with 5% carbon dioxide (CO2) inhalation. METHODS: The CO2 inhalation and consecutive 99mTc-HMPAO SPECT study was performed on 30 chronic ischemic cerebrovascular disease patients with unilateral major cerebral artery obstruction and on 27 patients without. CO2 reactivity was expressed as the percent increase of 99mTc-HMPAO accumulation from the baseline (%Change) and as a constant k' that was the ratio of 99mTc-HMPAO accumulation per 1 mmHg change of end-tidal CO2 tension by exponential curve fitting. RESULTS: The mean %Change and k' in the middle cerebral artery (MCA) territory on the side without an obstructive lesion or in the cerebellum ranged from 10.0% to 11.1% and from 0.98% to 1.13% per mmHg, respectively. In the MCA territory, an obstructive lesion was noted in 5.9% versus 0.54% per mmHg in the contralateral MCA territory (p < 0.01). Eleven of 30 patients with major cerebral artery obstruction revealed significant asymmetry in the k' value between bilateral MCA territories. CONCLUSION: The results showed compromised cerebral perfusion reserve in the obstructed major cerebral artery territory. The present method was proven clinically useful for evaluating cerebral perfusion reserve in patients with unilateral major cerebral artery obstruction.

Adult↗
PubMed1994

Electrical responses and K+ activity changes to light in the ocellus of the planarian Dugesia japonica.

The extracellular electrical response (ocellar potential, OP) and K+ activity changes to light were measured in the planarian ocellus by conventional and double-barreled ion-selective microelectrodes. The OP evoked by a 0.5 sec light flash is a simple monophasic potential, which is sustained during long-term illumination. The spectral sensitivity of the OP has the characteristics of a rhodopsin with lambda max 505 nm. K+ activity in the extracellular space of the ocellus in the dark was 1.1 +/- 0.2 mM (mean +/- SE, n = 6). A 0.5 sec light flash and a 120 sec long-term illumination evoked increases in the K+ activity. The maximum K+ activity change occurred at 503 nm. These results suggest that the efflux of K+ from the planarian photoreceptor into the extracellular space is caused by light, and that the OP and the increase of K+ activity are mediated by a rhodopsin.

Animals↗
PubMed1993

Molecular cloning of polymorphic markers on RLGS gel using the spot target cloning method.

A new method for target cloning of DNA fragments corresponding to spots on the two-dimensional restriction landmark genomic scanning (RLGS) profile has been developed (targeted spot cloning). We used a Not I restriction trapper to select target DNA fragments from Not I, Eco RV double digests of genomic DNA. The use of the restriction trapper substantially reduces the background clones that are established from the direct recovery of RLGS spot DNA from the two-dimensional gels. Genomic DNA clones were isolated in this study as mouse genome markers for 58 spot loci that were previously characterized using RLGS spot mapping. This method provides a powerful tool for isolating DNA clones after their identification by RLGS system.

Animals↗
PubMed1993

Restriction landmark genomic scanning method and its various applications.

We have developed a new genome scanning method (restriction landmark genomic scanning (RLGS), based on the new concept of using restriction enzyme sites as landmarks. RLGS employs direct end labeling of the genomic DNA digested with a restriction enzyme and two-dimensional electrophoresis with high-resolution. Its advantages are: (i) high-speed scanning ability, allowing simultaneous scanning of thousands of restriction landmarks; (ii) extension of the scanning field using different kinds of landmarks in an additional series of electrophoresis; (iii) application to any type of organism because of direct-labeling of restriction enzyme sites and no hybridization procedure; and (iv) reflection of the copy number of the restriction landmark by the spot intensity which enables distinction of haploid and diploid genomic DNAs. The RLGS method has various applications because it can be used to scan for physical genomic DNA states, such as amplification, deletion and methylation. The copy number of the locus of a restriction landmark can be estimated by the spot intensity to find either an amplified or deleted region. The methylation state of genomic DNA can also be discovered by use of a methylation-sensitive restriction enzyme sites as a restriction landmark (restriction landmark genomic scanning for screening methylated sites, RLGS-M). This article introduces the basic principle of RLGS and its applications to the analysis of cancer, mouse mutant DNAs and tissue-specific methylation, showing the usefulness of RLGS for a variety of biological fields.

Animals↗
PubMed1993

Characteristics of specific 125I-omega-conotoxin GVIA binding in rat whole brain.

Characteristics of specific 125I-omega-conotoxin (omega-CgTX) binding were systematically investigated in crude membranes from rat whole brain. Kd and Bmax Values for the binding were 49.7 pM and 181.5 fmol/mg of protein, respectively. The effects of various types of Ca channel antagonists on the binding were investigated. Dynorphin A (1-13), in particular, specifically inhibited 125I-omega-CgTX binding, but not that of [3H](+)PN200-110. Spider venom from Plectreurys tristes did not specifically inhibit specific binding of 125I-omega-CgTX, because the venom also inhibited the binding of [3H](+)PN200-110 to a similar degree. The amount of specific binding of 125I-omega-CgTX was less in the cerebellum than that in any other area of whole brain. The cross-linker disuccinimidyl suberate did not label with 125I-omega-CgTX and its binding sites in rat whole brain, although it did in chick whole brain, which was used as a positive control. These findings suggested that dynorphine A (1-13) was a selective blocker of omega-CgTX-sensitive Ca channels in crude membranes from rat whole brain and that omega-CgTX-sensitive Ca channels were mainly present a rat brain except cerebellum.

Animals↗
PubMed1993

The effect of 4-aminopyrazolo(3,4-d) pyrimidine on mouse plasma alpha-amylase activity.

A single dose of 4-aminopyrazolo(3,4-d) pyrimidine (4APP), an adenine analog, was orally administered at various concentrations of groups of mice and after 24 h, the plasma-alpha-amylase activity and cholesterol levels had significantly decreased in a dose-dependent manner. There was no change, however, in pancreatic superoxide dismutase activity or the lipid peroxide level. Histologically, zymogen degranulation was found after a high oral dose of 4APP (175 mg/kg). The same decrease in alpha-amylase activity occurred in mice that had received ip administration of 4APP, and in mice that were pretreated with dimethyl sulfoxide. Based on these results, it appears that 4APP decreases plasma alpha-amylase activity dose-dependently, possibly by pancreatic injury, and that free radicals play no part in the observed changes.

Adenine↗
PubMed1993

Zinc deficiency exaggerates diabetic osteoporosis.

Streptozotocin diabetic rats showed an increase of bone fragility (11.9 +/- 2.1 kg/cm2 vs. 16.8 +/- 2.0, P < 0.005) which was normalized by insulin treatment (18.3 +/- 4.2), indicating that osteoporosis was induced in diabetic rats. The rats were fed a zinc-deficient diet (0.16 mg/100 g) or a control diet (5.2 mg/100 g). This mild zinc-deficient diet did not lower the serum zinc level. The cortical bone of diabetic rats was shown to be markedly thinner by microscopic examination of ground cross-sections of the tibia. Zinc deficiency induced a reduction in the calcium content of diabetic bone when compared with the rats on a control diet. Urinary excretion of calcium and phosphorus was significantly increased in diabetic rats, and increased further when the rats were fed a zinc-deficient diet. Moreover. the bone calcium and phosphorus concentrations were significantly lower in these animals. These changes in the zinc-deficiency rats were not reversed by insulin treatment. Our findings suggest that osteoporosis in the diabetic rats was due to thinning of the bone cortex secondary to mineral loss and can be reversed by insulin treatment, and that these skeletal changes are greatly enhanced by mild zinc deficiency. In addition the effects of zinc deficiency cannot be completely reversed by insulin treatment.

Alkaline Phosphatase↗
PubMed1993

Attenuation of increased regional myocardial oxygen consumption during exercise as a major cause of warm-up phenomenon.

OBJECTIVES: The aim of this study was to test the hypothesis that the warm-up phenomenon is attributable to a reduction of increased myocardial oxygen consumption rather than to increased coronary blood flow during exercise. BACKGROUND: The underlying mechanism of the warm-up phenomenon is not elucidated. METHODS: Thirteen patients with effort angina were subjected to two consecutive supine ergometer exercise tests performed 15 min apart. All patients had severe proximal stenosis (> 90%) in the left anterior descending coronary artery. Great cardiac vein flow was measured before and during exercise. Both regional myocardial oxygen consumption and adenosine release were determined. RESULTS: Exercise was continued for significantly longer before angina onset in the second than in the first exercise test (507 +/- 44 vs. 410 +/- 42 s, p < 0.01). The extent of ST segment depression in lead V5 of the electrocardiogram (ECG) was larger at the time of angina onset in the first (1.7 +/- 0.2 mm) than in the second (1.1 +/- 0.2 mm, p < 0.01) exercise test. Neither systemic hemodynamic variables nor great cardiac vein flow differed between the first and second exercise tests. In contrast, regional myocardial oxygen consumption assessed at 3 min of exercise was significantly (p < 0.01) less in the second than in the first test (8.0 +/- 0.8 vs. 8.7 +/- 0.9 ml/min). Adenosine release during the second test was higher (p < 0.05) than in the first test (2.5 +/- 0.5 vs. 3.9 +/- 0.5 nmol/min at 3 min of the first and second tests, p < 0.01). CONCLUSIONS: These results indicate that the warm-up phenomenon is not attributable to increased coronary flow but to attenuation of increased regional myocardial oxygen consumption, which may be mediated by adenosine A1 receptor activation.

Adaptation, Physiological↗
PubMed1993

Role of metallothionein in 4-aminopyrazolo[3,4-d]pyrimidine-administered mouse pancreas.

Pancreatic metallothionein (MT) and zinc levels were measured after the administration of 4-aminopyrazolo(3,4-d)pyrimidine (4APP) to mice to determine the role of pancreatic MT. 4APP was found to increase the pancreatic MT level dose-dependently; the pancreatic MT level in mice administered 175 mg/kg of 4APP was 3.9 fold higher than that in control mice. When 40 mg/kg or less of 4APP was administered, the zinc concentration of the pancreatic cytosol fraction did not differ from that in control mice, while after 175 mg/kg of 4APP it was 1.7-fold higher. There was no difference in plasma glucose and insulin levels between the controls and mice administered 175 mg/kg of 4APP, although the plasma alpha-amylase activity was reduced in the latter. Moreover, a linear negative relationship was observed between pancreatic MT level and plasma alpha-amylase activity (r = -0.795, p < 0.01). These findings suggest that pancreatic MT is affected by the disruption of the exocrine function in 4APP-administered mouse pancreas.

Adenine↗