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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 811 records · Page 45Linked to original sources
PubMed1995

Preoperative diagnosis of a small, depressed rectal cancer complicating ulcerative colitis. Report of a case.

PURPOSE: This study was designed to clarify the importance of detecting small, depressed colorectal cancer complicating ulcerative colitis. METHODS: A 39-year-old Japanese male, who had an 18-year history of left-sided ulcerative colitis, was admitted to Fukuoka University Hospital for further evaluation of his colitis. Colonoscopy with a dye spraying method clearly revealed a small, depressed lesion and flat plaque-like lesions in the rectum. Biopsies taken from a depressed lesion and plaque-like lesions revealed a signet-ring cell carcinoma and dysplasia, respectively. Total colectomy was performed. RESULTS: Sections from the depressed rectal lesion, measuring 7 x 8 mm in size, revealed a signet-ring cell carcinoma that diffusely invaded the muscularis propria. Lymph node metastasis was evident. Flat plaques and mucosa around the depressed lesion were positive for dysplasia. CONCLUSION: This is the first report of a case of small, depressed rectal cancer complicating ulcerative colitis diagnosed by preoperative colonoscopy. To improve outcome of colonoscopic surveillance in ulcerative colitis, detecting such small, depressed lesions are important, and colonoscopy with a dye spraying method would be useful in detecting them.

Adult↗
PubMed1995

Successful 24-hour rabbit heart preservation by hypothermic continuous coronary microperfusion with oxygenated University of Wisconsin Solution.

BACKGROUND: This study assessed whether a combination of hypothermic continuous coronary microperfusion and oxygenated University of Wisconsin Solution (UWS) improves postischemic functional recovery and minimizes myocardial tissue edema. METHODS: Isolated rabbit hearts were divided into four groups (n = 6 each): group I (immediate reperfusion), group II (simple cold storage in UWS), group III (hypothermic continuous coronary microperfusion with UWS), and group IV (hypothermic continuous coronary microperfusion with oxygenated UWS). Hearts in groups II, III, and IV were preserved for 24 hours. Preischemic and postischemic cardiac function was measured using a Langendorff apparatus. RESULTS: Hearts in group I showed complete functional recovery, whereas cardiac output in group II was inadequate. In groups III and IV, the percentage recovery rate (post/pre) of cardiac output was 57.0% +/- 3.1% and 82.2% +/- 9.1%, respectively (p < 0.05). In groups III and IV, perfusion pressures at the end of 24-hour preservation increased from the initial 5 mm Hg to 12.3 +/- 2.7 and 8.3 +/- 1.4 mm Hg (p < 0.05), respectively. In groups I, III, and IV, the percentage tissue water content was 82.8 +/- 1.0, 86.7 +/- 1.7, and 83.8 +/- 1.6, respectively (p < 0.05 for group III versus groups I and IV). There was a significant correlation between the percentage tissue water content and coronary perfusion pressure at the end of the 24-hour preservation (r = 0.60, p = 0.040) and a significant inverse correlation between percentage tissue water content and percentage recovery rate of cardiac output (r = -0.69, p = 0.014). In ultrastructural examination, myocardial tissue edema was limited and mitochondria were well preserved in group IV. CONCLUSION: We conclude that the combination of a hypothermic continuous coronary microperfusion technique and oxygenation of UWS was the procedure of choice for reducing tissue edema and improving both the coronary microcirculation and functional recovery during 24-hour heart preservation.

Adenosine↗
PubMed1995

Mutations of the p53 gene in myelodysplastic syndrome and overt leukemia.

We analysed p53 mutations in 24 patients with myelodysplastic syndrome (MDS) and overt acute myeloid leukaemia after a period of MDS, using polymerase chain reaction-single strand conformation polymorphism analysis. In exons 5 to 8, mobility shifts were detected in five of the 24 patients. Sequence analysis was subsequently performed, and four missense mutations (16.7%) and one silent nucleotide substitution were identified. Patients harbouring mutations were characterized as having advanced disease. Loss of the wild type allele was observed in three of the four patients with missense mutations. No mobility shifts of the N-ras or FMS gene were detected in these four patients. We next analysed the correlation of the p53 mutations with the progression of MDS in three patients. The mutation was accompanied by the progression in two of the three patients. These findings suggest that mutations of the p53 gene are associated with progression in some cases of MDS, while being compatible with stable disease or clonal evolution in others.

Base Sequence↗
PubMed1995

Correlation between anti-ubiquitin immunoreactivity and region-specific neuronal death in N-methyl-D-aspartate-treated rat hippocampal organotypic cultures.

Neuronal degeneration appears to be associated with changes in anti-ubiquitin immunoreactivity (UIR). To elucidate the relationship between the two events, we examined the time course of changes in UIR in pyramidal neurons of hippocampal organotypic cultures following exposure to an excitotoxin, N-methyl-D-aspartate (NMDA). In nontreated cultures, weak UIR was confined to the nucleus. Exposure to 100 microM NMDA for 15 min induced degeneration of pyramidal neurons, within 24 h, in the CA1 and CA3c regions. In these neurons, the nuclear UIR was reduced, and instead, UIR developed in the cytoplasm. In response to the same procedure, CA3a,b pyramidal neurons showed slight shrinkage but otherwise virtually normal morphological features. Little perikaryal (cytoplasmic) UIR developed in CA3a,b neurons. Both degeneration and perikaryal UIR were observed in CA3a,b neurons, however, when the culture was exposed to 300 microM NMDA. Immunoblot analysis showed that changes in the amount of a ubiquitin protein conjugate (24 kDa), presumably ubiquitinated histone, are similar to those of nuclear UIR in the same time course. We propose that the changes in the expression of nuclear and perikaryal ubiquitinated proteins represent some process closely related to neuronal death.

Animals↗
PubMed1995

IntroStat: a hypertext-based design for an electronic textbook to introduce biomedical statistics.

A hypertext-based system called IntroStat has been developed to introduce fundamental methods of biomedical statistics. The system has been developed on a Macintosh II using HyperCard. It is written mainly in Hypertalk, a scripting language of HyperCard. Being an electronic textbook of probability and statistics, the system features computational capabilities. At the end of the sections describing basic methods of statistics, pages are provided where a user may enter data and try the methods right there. Some means for branching are provided for easy access to a page of interest, including branching by contents, by index, and by keyword reference. The system design is proposed as a model of an electronic textbook for biomedical statistics.

Biometry↗
PubMed1995

Analysis of biological function of poly(ADP-ribosyl)ation in Drosophila melanogaster.

To understand the biological function of poly(ADP-ribosyl)ation of proteins, we have isolated and characterized the gene for poly(ADP-ribose) polymerase from Drosophila melanogaster. Two approaches were taken to analyze the function of the poly(ADP-ribosyl)ation reaction. The first is analysis of the homology of the amino acid sequences of poly(ADP-ribose) polymerase from phylogenetically different eukaryotes, namely human, mouse, bovine, chicken, Xenopus laevis and Drosophila melanogaster and elucidation of the conserved amino acid sequences that appear to be important for the function of poly(ADP-ribose) polymerase. Analysis of the recombinant poly(ADP-ribose) polymerase which had truncated or mutated motifs expressed in E coli would confirm the importance of the conserved amino acid sequence. The interaction of poly(ADP-ribose) polymerase with other proteins involved in DNA repair, replication, recombination and transcription will clarify the function of poly(ADP-ribosyl)ation. The second approach is to get the mutants which have disruption in the poly(ADP-ribose) polymerase gene and to analyse the phenotypes of these mutants. The characterization of these mutants will be discussed.

Amino Acid Sequence↗
PubMed1995

Endothelin receptor antagonists in a beagle model of pulmonary hypertension: contribution to possible potential therapy?

OBJECTIVES: This study investigated the pharmacologic effect of endothelin receptor antagonists on cardiopulmonary hemodynamic variables in a beagle model of pulmonary hypertension. BACKGROUND: We recently developed a beagle model of pulmonary hypertension that allows accurate determination of cardiopulmonary hemodynamic variables and is associated with elevated plasma endothelin-1 concentrations similar to those in pulmonary hypertension in humans. METHODS: Twelve beagles (pulmonary hypertension, n = 6; control group, n = 6) were studied during baseline conditions and during right atrial infusion of FR139317 (an ETA receptor antagonist), RES-701-1 (an ETB receptor antagonist), nitroglycerin and prostaglandin E1. Pulmonary hypertension was induced in experimental beagles 8 weeks after injection with 3 mg/kg body weight of dehydromonocrotaline. RESULTS: FR139317 lowered pulmonary artery and systemic arterial pressures in both pulmonary hypertensive and control beagles, with a significantly greater effect on pulmonary artery pressure in pulmonary hypertensive dogs. RES-701-1 tended to increase pulmonary artery pressure only in pulmonary hypertensive beagles. Nitroglycerin depressed pulmonary artery and systemic arterial tone equally well in control and pulmonary hypertensive animals. Prostaglandin E1 produced a greater decrease in systemic arterial pressure in pulmonary hypertensive than in normal beagles despite having the same effect on pulmonary artery pressure in both. CONCLUSIONS: ETA receptor antagonists decrease pulmonary artery pressure in a beagle model and may therefore be clinically useful for treatment of pulmonary hypertension.

Alprostadil↗
PubMed1995

Effects of zonisamide on dopaminergic system.

Effects of zonisamide (ZNS) on extracellular dopamine (DA), its precursor 3,4-dihydroxyphenylalanine (DOPA), its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in the striatum as well as hippocampus of freely moving rats were studied. Intracellular DA, DOPA, DOPAC and HVA levels, as well as DOPA accumulation as an index of tyrosine hydroxylase activity in the rat brain in vivo, DA re-uptake in the striatum and hippocampus, and monoamine oxidase (MAO) activities were also determined. Acute administrations of therapeutic ZNS doses (20 and 50 mg/kg) increased striatal extracellular DOPA levels, intracellular striatal and hippocampal DOPA levels, and stimulated DOPA accumulation in both brain regions. ZNS also increased striatal and hippocampal intracellular as well as extracellular DA and HVA levels, but decreased those of DOPAC levels. Chronic (3 weeks) administrations of therapeutic ZNS doses (20 and 50 mg/kg/day) increased intracellular DA, DOPA, DOPAC and HVA levels in striatum and hippocampus. ZNS-induced changes were greater in intracellular levels than in extracellular levels. Acute and chronic supratherapeutic ZNS dose (100 mg/kg) administration decreased intracellular levels of all substances detectable in both brain regions, and inhibited DOPA accumulation. Both subtypes of MAO (type A and type B) activities were weakly inhibited by ZNS. ZNS showed no effect on DA re-uptake in striatum nor in hippocampus. These results suggest that therapeutic ZNS doses increase DOPA accumulation as well as both intracellular and extracellular DA, DOPA and HVA levels. However, such doses also decrease extracellular and intracellular DOPAC levels by enhancing DA synthesis and/or by selectively inhibiting MAO-B activities. In addition, chronic therapeutic ZNS dose administration enhances DA synthesis, which results in increased intracellular DA, its precursor and its metabolites levels. On the other hand, both acute and chronic supratherapeutic ZNS dose administrations inhibit DA turnover. These ZNS effects on DA metabolism are at least partly involved in the mechanisms of action of ZNS.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

The potent and selective inhibition of estrogen production by non-steroidal aromatase inhibitor, YM511.

YM511 inhibited aromatase activities in microsomes from rat ovary and human placenta competitively (IC50s: 0.4 and 0.12 nM, respectively). YM511 was about 3 times more potent than other aromatase inhibitors, such as CGS 16949A, CGS 20267 and R 76713. YM511 decreased the contents of estradiol stimulated by pregnant mare's serum gonadotropin in rat ovary with an ED50 of 0.002 mg/kg, indicating that YM511 was equipotent to CGS 20267 and 3 times more potent than the other two inhibitors. Serum estradiol levels in female rats were reduced by YM511 at 0.01 mg/kg into the ovariectomized range. YM511 at 1 mg/kg for 2 weeks decreased rat uterine weight to levels comparable to ovariectomy, showing it was 10 times more potent than other inhibitors. But the maximal inhibitory effect of tamoxifen failed to reach ovariectomized level. YM511 slightly inhibited production of other steroid hormones in vitro and in vivo. The IC50s of YM511 for aldosterone and cortisol production from adrenal cells were from 5500 to 9800 times higher than that for rat ovarian aromatase and 130,000 times higher for testosterone production, indicating that YM511 is a highly specific aromatase inhibitor. The data suggest that YM511 may be a potent and selective agent for suppressing estrogen-dependent action without affecting serum levels of other steroid hormones.

Animals↗
PubMed1995

Successful surgical treatment of aortocaval fistula using cardiopulmonary bypass.

Aortocaval fistula caused by rupture of an abdominal aneurysm was diagnosed before surgery and treated successfully using cardiopulmonary bypass, which effectively controlled the massive bleeding. Rupture of the false lumen of a dissecting aneurysm limited to the abdominal aorta was responsible for the aortocaval fistula. The defect of the inferior vena cava was closed with a running suture and the aneurysm replaced with a collagen-coated Y graft.

Aged↗
PubMed1995

Pharmacologic intervention for ischemic brain edema after retrograde cerebral perfusion.

Retrograde cerebral perfusion has recently been the focus of interest as a simple new technique of brain protection during aortic arch operations. We undertook the experimental protocol of 120 minutes of retrograde cerebral perfusion followed by antegrade reperfusion. Eighteen mongrel dogs were used. Retrograde cerebral perfusion was maintained at a flow rate of 150 to 250 ml/min to keep the perfusion pressure from 15 to 25 mm Hg. Animals were divided into three groups as follows: in group I, no treatment was received during and after retrograde cerebral perfusion; in group II, mannitol (2 gm/kg) was administered before cardiopulmonary bypass was restarted; and in group III, antivasospastic substance (1,2-bis nicotinamido]-propane) was continuously injected during and after retrograde cerebral perfusion (1 mg/kg per minute). Cerebral blood flow decreased during retrograde cerebral perfusion in all three groups. Cerebrovascular resistance showed marked increases 30 and 60 minutes after cardiopulmonary bypass was restarted in group I compared with the values in groups II and III (group I: 3.35 +/- 0.73 and 5.00 +/- 1.57 mm Hg/ml per 100 gm per minute; group II: 1.30 +/- 0.33 and 1.03 +/- 0.17 mm Hg/ml per 100 gm per minute; group III: 1.24 +/- 0.41 and 0.98 +/- 0.24 mm Hg/ml per 100 gm per minute). The oxygen extraction level was reduced by cooling, but it rose to a higher level as a result of significant desaturation of returned blood even in deep hypothermia during retrograde cerebral perfusion. Both cerebral metabolic rate of oxygen and cerebral metabolic rate of glucose remained at low levels during retrograde cerebral perfusion. Ratios of cerebral blood flow to cerebral metabolic rate of oxygen and cerebral blood flow to cerebral metabolic rate of glucose were markedly reduced during retrograde cerebral perfusion. Intracranial pressure showed significant increases 30 and 60 minutes after cardiopulmonary bypass was restarted in group I compared with values in group II or group III (group I: 22.7 +/- 2.8 and 20.6 +/- 5.1 mm Hg; group II: 6.3 +/- 1.8 and 5.3 +/- 1.3 mm Hg; group III: 4.2 +/- 1.7 and 7.7 +/- 2.8 mm Hg). Water content of the brain tissue in group I (77.54% +/- 0.29%) was significantly higher than that in group II (74.71% +/- 0.76%) or group III (74.14% +/- 0.48%). These data suggest that the supply of oxygen or glucose by retrograde cerebral perfusion is not enough to maintain sufficient cerebral metabolism, which may cause brain edema during antegrade reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Antitumoral efficacy and pharmacokinetic properties of pirarubicin upon hepatic intra-arterial injection in the rabbit V x 2 tumour model.

To improve the efficiency of hepatic intra-arterial (h.i.a.) chemotherapy, we selected pirarubicin (THP) because it shows good properties for h.i.a. chemotherapy, such as fast and efficient cellular uptake, and used it for h.i.a. chemotherapy in rabbits with V x 2 tumour implanted in the liver. The anti-tumour effect of THP upon h.i.a. administration was compared with that upon intravenous (i.v.) injection and also with the anti-tumour activity of epirubicin (EPI) upon h.i.a. injection using optimal and maximal tolerated doses of each drug. When tumour growth rates and morphometric examinations were evaluated, it was found that THP and EPI were effective against V x 2 tumour when injected via the h.i.a. route. The activity of THP was stronger than that of EPI. As regards h.i.a. injection-related complication, plasma transaminase levels were temporarily elevated. To demonstrate higher anti-tumour activity and other advantages of h.i.a. injection of THP, plasma and tumour drug concentrations were determined by high-performance liquid chromatography after THP or EPI was administered at an equal dose to the rabbit V x 2 model. Hepatic intra-arterial injection of THP accomplished a selective and higher uptake into the tumour and lower effusion into the plasma than i.v. injection of THP or h.i.a. injection of EPL. Our findings indicate that THP is the better candidate of the two drugs tested for the h.i.a. chemotherapy because of its greater anti-tumour activity and the lower systemic drug exposure achieved upon h.i.a. injection.

Animals↗
PubMed1995

Long-term spatial cognitive impairment after middle cerebral artery occlusion in rats: no involvement of the hippocampus.

The behavioral and neurochemical changes in the chronic phase of permanent occlusion of the right middle cerebral artery (MCA) in rats were investigated. One month after MCA occlusion, 23 rats were unable to solve a radial eight-arm maze task during an entire 1-month period, whereas seven rats were able to solve this task. Three months after occlusion, 19 MCA-occluded rats failed to solve the task successfully again for at least 1 month (the cognitively impaired rats), whereas 11 MCA-occluded rats were able to solve it (the cognitively unimpaired rats). The rats that underwent behavioral testing were examined for any changes in the acetylcholine (ACh) levels in the hippocampus using HPLC with electrochemical detection or the formation of long-term potentiation (LTP) in the population spike of the hippocampal CA1 field. The immunohistochemical distribution of either the microtubule-associated protein 2 (MAP2) or glial fibrillary acidic protein (GFAP) in the hippocampus of the cognitively impaired rats was also studied. In the cognitively impaired rats, neither the suppression of the induction of LTP, nor the degradation of MAP2, nor the increase in the GFAP immunoreactivity was observed in the hippocampus. The levels of ACh in the hippocampus did not change significantly among the cognitively impaired, unimpaired, and the sham-operated rats. These results suggest that MCA occlusion is capable of producing long-term spatial cognitive disturbance in rats without any evidence of neurobiological damage in the hippocampus.

Acetylcholine↗
PubMed1995

Long-term spatial cognitive impairment following middle cerebral artery occlusion in rats. A behavioral study.

Behavioral changes in the chronic phase of permanent occlusion of the right middle cerebral artery (MCA) in rats were investigated. One month after MCA occlusion, 23 rats were unable and 7 rats were able to solve a radial 8-arm maze task during a 1-month period. Three months after occlusion, 19 MCA-occluded rats failed to solve the task successfully again during at least a 1-month period (the cognitively impaired rats), and 11 MCA-occluded rats were able to solve it (the cognitively unimpaired rats). When a delay of 60 min was imposed for this task, five cognitively unimpaired rats failed to solve it. The locomotor activity of the cognitively impaired rats increased significantly 2 months after occlusion, and this increase showed good correlation with spatial cognitive deficit. However, the mean time a rat spent at each arm remained unchanged among the cognitively impaired, unimpaired, and sham-operated rats. There was no significant difference in the ratio between the cognitively impaired and unimpaired rats for disturbed motor coordination. These results suggest that MCA occlusion is capable of producing long-term spatial cognitive disturbance in rats. In addition, this spatial cognitive deficit does not seem to be primarily due to hypermotility or a disturbance in motor coordination.

Animals↗