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Biomedical subjects

T Fukuhara

Publications and source records attributed to T Fukuhara.

At least 73 records · Page 4Linked to original sources

Induction of Cu,Zn-superoxide dismutase after cortical contusion injury during hypothermia.

To determine the effect of hypothermia on superoxide injury after cerebral contusion, the induction of Cu,Zn-superoxide dismutase was examined 6 h after contusion in rats using Northern blotting. Cu,Zn-superoxide dismutase gene expression increased at the periphery of the contusion, which may indicate the severity of the superoxide stimulus. This increase was preserved after contusion under hypothermia, which may show that superoxide injury is still severe although brain edema is decreased.

Animals↗

Detection of endogenous albumin as an index of blood parenchymal border alteration.

We used a microdialysis technique to establish a method to detect sequential changes in disruption of the blood parenchymal border. Twelve cats were divided into two groups; one group underwent occlusion of the middle cerebral artery for 60 minutes, the other a cold injury model. Microdialysis probes were implanted bilaterally into the white matter, and dialysates were collected successively at 30 minute intervals for 6 hours in the occlusion model and 4 hours in the cold injury model. Regional cerebral blood flow was measured simultaneously using the hydrogen clearance method. The water content of the white matter was measured using specific gravity. The proteins in the dialysate were analyzed using electrophoresis with silver stain, and, with densitometric analysis, the density of the 66.2 kDa band was quantified as albumin. The ratio of this density to the preoperative density was defined as the "albumin index." On the side of the lesion in the cold injury model, this index significantly increased 3 hours after the cold injury compared with the contralateral side, and a correlation between the water content and this index was observed. The albumin index was believed to indicate the severity of disruption of the blood parenchymal border.

Animals↗

Endogenous superoxide dismutase activity in reperfusion injuries.

To elucidate the relationship between reperfusion injuries and free radicals, we monitored the endogenous superoxide dismutase (SOD) activity by intracerebral microdialysis. Six cats underwent a transient occlusion of the middle cerebral artery for 60 minutes after microdialysis probes were implanted bilaterally into the white matter under the ectosylvian gyrus. Dialysates were collected at 30 minute intervals over the course of 5 hours after reperfusion. The SOD activity of the dialysates was measured with electron spin resonance spectrometry. Regional cerebral blood flow was measured simultaneously and the water content of the white matter was assayed at the end of the experiment. After reperfusion, SOD activity increased significantly in the first 30 minutes compared with the preoperative value, and decreased over 4-4.5 hours and 4.5-5 hours in the occluded side. The water content in the occluded side was significantly higher than that in the contralateral side. The highest SOD activity during reperfusion and the water content in the occluded side seemed to correlate, although not significantly. A leakage of intracellular SOD or a reactive increase of SOD activity in response to the reperfusion injury are possible mechanisms of increase in extracellular SOD.

Animals↗

Superoxide scavenging activity in vitro and in the cerebral extracellular space measured by microdialysis.

Using the electron spin resonance (ESR) spin-trapping method and a high molecular cut-off membrane, we measured the superoxide scavenging activity in dialysates obtained from microdialysis. The activity in the dialysates of the Cu,Zn-superoxide dismutase (SOD) solution and feline serum were measured in vitro, and the recovery rate was calculated to be 12.88 +/- 0.9% in Cu,Zn-SOD solution and 21.52 +/- 4.38 in feline serum, which was significantly different. This difference was believed to originate from the higher osmotic pressure due to proteins in the serum and substances other than Cu,Zn-SOD that acted as antioxidants in the serum. In an in vivo study, microdialysis probes were implanted into the cerebral hemispheres in 6 cats. The sequential changes of superoxide scavenging activity were measured for 16 h and during induced cardiac arrest. No significant difference was observed and the microdialysis technique itself did not seem to cause the significant alteration of the activity in the extracellular space, although at cardiac arrest, the activity varied widely. This method can be used to study the reaction against superoxide injury in further experiments involving brain insult.

Animals↗

Cancer incidence in Hiroshima and Nagasaki, Japan, 1958-1987.

The Hiroshima and Nagasaki tumour registries, which have been in operation since 1958, are among the few population-based cancer registries in Japan. This analysis evaluated cancer incidence in Hiroshima and Nagasaki between 1958 and 1987. The overall age-adjusted (World Population Standard) cancer incidence has increased from 217 to 301 per 100,000 among males, and from 176 to 197 per 100,000 among females during the first 30 years of cancer registration. The most recent rates are intermediate to rates in other countries. Despite a gradual decrease, gastric cancer remained the most common malignancy among males and females throughout the surveillance period, accounting for 24% of all cancers by the late 1980s. The rate of liver cancer has increased dramatically among males during the past 20 years, with a 2-fold increase in incidence in the past 10 years alone. The populations of Hiroshima and Nagasaki now have among the highest rates of liver cancer in the world. Breast cancer incidence in Hiroshima and Nagasaki, in contrast, is among the lowest in the world, although incidence rates have doubled since the 1960s. Other common malignancies include cancers of the lung, colon and rectum among males and cancers of the colon, cervix and lung among females.

Adolescent↗

Superoxide scavenging activity in the extracellular space of the brain in forming edema.

We carried out a time course study of cerebral superoxide scavenging activity using a modified microdialysis technique. Twelve cats were divided into two groups; six were the reperfusion injury models, and six were cold injury models. In the reperfusion injury model, dialysates were collected during 60 minutes of middle cerebral artery occlusion and at 300 minutes during reperfusion. In the cold injury model, dialysates were collected 240 minutes after the injury. Regional cerebral blood flow on the injured side decreased during occlusion in the reperfusion injury model and 60 minutes after injury in the cold injury model. In the reperfusion model, superoxide scavenging activity, as determined with electron spin resonance, increased in the first 30 minutes and decreased 300 and 330 minutes after occlusion. In the dialysate, albumin increased 180 minutes after cold injury, which may show the progress of vasogenic edema. An increase in water content was observed on the injured side of both models, and a correlation between water content and superoxide scavenging activity was found in the reperfusion injury model. By this technique, a method of detecting the alteration of superoxide scavenging activity in the extracellular space of the brain was established.

Animals↗

Experimental analysis of brain surface elastance in cats.

Brain surface elastance, defined as the pressure needed to compress the cortex 3 mm, was measured using the ophthalmodynamometer in six cats using three burr holes (frontal, parietal, and occipital) on each side. An intracranial mass was then used to compress the right side for 3 hours, and cardiac arrest was induced after the mass was removed. Elastance was measured four times: before insertion of the mass, 10 and 70 minutes after removal of the mass, and 60 minutes after cardiac arrest. The results showed that: brain surface elastance does not change between sides, but varies among regions with the parietal region having the highest elastance; elastance increases after compression by an intracranial mass, but not after cardiac arrest; and stiff brain tends to restore poorly. Elastance is apparently increased by the formation of edema. Measuring brain elastance may be useful in predicting brain restoration subsequent to removal of mass lesions.

Animals↗

End-to-end duodenojejunal bypass for unresectable periampullary carcinoma.

Palliative operation plays an important part in the treatment of periampullary carcinoma. However, gastric bypass such as the widely practiced side-to-side gastrojejunostomy frequently fails to provide adequate drainage. Here we attempted to fashion an end-to-end duodenojejunostomy in the hope of establishing physiological continuity of the stomach and duodenum. Biliary bypass with side-to-side choledochojejunostomy is performed simultaneously. Eight patients underwent this surgery. In seven of these, radical resection proved to be impossible, and in one the duodeno-biliary decompression was attempted before the radical operation. Early results were satisfactory in all patients. They began to eat liquid meals within a week, and were discharged uneventfully within the third postoperative week, when they were able to eat a regular diet. No ulcer developed in any of the patients. Plasma gastrin levels following a test meal was significantly lower after the operation, but plasma CCK-N and GIP levels showed no statistical difference prior to and after surgery. This duodenojejunal bypass is recommended as a means of improving the quality of the remaining life of the patients.

Aged↗

[Neoadjuvant chemotherapy for elderly advanced gastric cancer: a case report of MTX/5-FU sequential therapy followed by radical gastrectomy].

A 70-year-old-male was diagnosed as having gastric cancer (Borr. 2, 78 mm in size on the body region; mod. dif. adenocarcinoma). CT scan revealed direct invasion of the liver. A course of MTX/5-FU sequential therapy was started (MTX 100 mg/m2, 5-FU 500 mg/m2, i.v., weekly; interval, 2 hours) on March 23, 1992. The gastric tumor showed 67% reduction on week 8 and 86% on week 10. The liver invasion had almost disappeared by CT scan (total doses, MTX 1,040 mg, 5-FU 6,750 mg). On June 25, the tumor was completely resected by radical.gastrectomy. The pathological specimen showed a "submucosal carcinoma" (10 mm in size, Stage I). Twenty-two months after the operation, the patient is alive and in good health. No cancer recurrence has been found without post-operative chemotherapy.

Adenocarcinoma↗

Different mechanisms of inhibition by alkyl-lysophospholipid and phorbol ester of granulocyte-macrophage colony-stimulating factor binding to human leukemic cell lines.

We investigated the effects of rac-1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine (ET-18-OCH3) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on granulocyte-macrophage colony-stimulating factor (GM-CSF) binding to human leukemic cell lines HL60, U937, KG-1, KG-1a, and K562. HL60, U937, and KG-1 exhibited the high-affinity receptors, but KG-1a and K562 revealed no demonstrable receptors. ET-18-OCH3 inhibited GM-CSF binding to HL60, U937, and KG-1 cells with a half-maximal inhibitory concentration of 16, 10, and 78 microM, respectively. ET-18-OCH3 at 10 microM reduced GM-CSF binding sites on HL60, U937, and KG-1, but had little effect on the dissociation constant (Kd). ET-18-OCH3 at 10 and 30 microM significantly (p < 0.01) decreased, in a dose-dependent manner, the total uptake, surface binding, and internalization of GM-CSF. The internalization of GM-CSF was more profoundly inhibited than its surface binding. TPA at 1 and 10 nM inhibited GM-CSF binding. Inhibition of GM-CSF binding by a combination of ET-18-OCH3 (10 microM) and TPA (1 or 10 nM) was less than additive, and ET-18-OCH3 partially inhibited TPA-induced protein kinase C (PKC) depletion in the cytosol and translocation to the particulate fractions. It is suggested that the inhibition of GM-CSF binding by ET-18-OCH3 is due in part to disruption of the plasma membrane and that the inhibition of GM-CSF binding by TPA is due to activation of PKC.

Antineoplastic Agents↗

Enigmatic double-stranded RNA in Japonica rice.

We have found a linear, 16 kb, double-stranded RNA (dsRNA) in symptomless Japonica rice (Oryza sativa L.) that is not found in Indica rice (Oryza sativa L.). The dsRNA was detected in every tissue and at every developmental stage, and its copy number was approximately constant (about 20 copies/cell). Double-stranded RNA was also detected in two strains of Oryza rufipogon (an ancestor of O. sativa). Hybridization experiments indicated that the dsRNA of O. rufipogon was homologous but not identical to that of O. sativa. The sequence of about 13.2 kb of the dsRNA was determined and two open reading frames (ORFs) were found. The larger ORF (ORF B) was more than 12,351 nucleotides long and encoded more than 4,117 amino acid residues.

Base Sequence↗

A case of pontine lacunar infarction with ulcerative colitis.

We present the case of a young man who experienced a sudden onset of pure motor hemiplegia in association with ulcerative colitis. Based on a review of earlier reports, ulcerative colitis was suspected to be the background disease leading to cerebral infarction. A cerebral infarction of the lacunar type in the right ventromedial aspect of the upper pons was seen on magnetic resonance images. These images detected small lesions in the brain stem, and were used to follow-up their transitions.

Adolescent↗

Increased capillary permeability to albumin in diabetic rat myocardium.

To clarify the mechanism for the well-known increase in microvascular permeability that occurs with diabetes mellitus, we investigated capillary permeability to albumin in diabetic rat myocardium by electron microscopy using albumin-gold (Alb-Au) complexes as a tracer. Diabetes was induced by an intravenous injection of streptozotocin. After 24-32 weeks, hearts from diabetic rats and age-matched control rats were perfused with Krebs-Henseleit bicarbonate buffer containing Alb-Au for 5 or 20 minutes and then fixed and processed for electron microscopy. The binding and transport of Alb-Au by capillary endothelium was quantitatively evaluated. In control rats, Alb-Au particles were found preferentially bound to the luminal plasmalemmal vesicles. In diabetic rats, the labeling of luminal vesicles was more extensive and more pronounced after 5 minutes of perfusion when compared with control vesicles. The plasma membrane proper was also heavily labeled in diabetic rats. After 20 minutes, Alb-Au particles were transported across the capillary endothelium via plasmalemmal vesicles, but they did not penetrate the intercellular junctions in either control or diabetic rats. The vesicular transport of Alb-Au across the capillary endothelium was significantly increased in the diabetic myocardium when compared with control myocardium (percentage of abluminal labeled vesicles, 25.9 +/- 5.5% versus 1.3 +/- 0.5%; p < 0.01). The study on food-restricted rats with body weights close to those of diabetic rats suggested that caloric deficiency alone did not have much effect on capillary permeability. The data indicate that capillary permeability to albumin is markedly increased in diabetic myocardium because of enhanced vesicular transport. This may play an important role in the pathogenesis of diabetic cardiomyopathy.

Animals↗

[A case of intra- and extracranially extensive metastatic brain tumor of tracheal cancer origin].

The authors report a case of metastatic brain tumor of tracheal cancer origin, itself a rare condition. A 55-year-old man was admitted with complaints of headache, atonic seizure of left lower limb and right temporal swelling. On admission, the patient had left recurrent nerve palsy. CT scan displayed right temporal bone destruction and ring-enhanced mass. MRI disclosed that the mass contained an inner necrotic region and a perifocal edema. Right common carotid angiogram revealed that the tumor was fed only by narrowed vessels of the middle meningeal artery. Subtotal removal of the tumor was performed, and histological examination revealed cranial metastasis of tracheal squamous cell carcinoma. Postoperative course was uneventful, and the patient underwent medical treatment for the primary lesion before post-operative brain-irradiation.

Brain Neoplasms↗

Use of the polymerase chain reaction to detect hypermethylation in the calcitonin gene. A new, sensitive approach to monitor tumor cells in acute myelogenous leukemia.

Based on the recent observations that, in a majority of patients with acute leukemia, the 5' end of the calcitonin gene was hypermethylated and abnormal DNA fragments were observed following HpaII restriction digestion, we have developed a PCR-based method to sensitively detect this abnormal methylation of the calcitonin gene in AML. Applying the concept of competitive PCR, a semi-quantitative correlation was obtained between the amount of hypermethylation and the amount of leukemic cells present. These results suggest that this method will be useful to monitor the amount of tumor cells in bone marrow from patients with AML.

Base Sequence↗

[Cardiac sarcoidosis with multinucleated giant cells detected in endomyocardial biopsy specimens: report of 3 cases].

This is a report of 3 cases of cardiac sarcoidosis. None of the 3 patients had other overt systemic involvement. Multinucleated giant cells and non-caseating epithelial cell granulomas with small lymphocytic infiltrations were detected in the endomyocardial biopsy specimen. Some focal left ventricular wall motion abnormalities were detected by echocardiography and angiography in all 3 patients. Paroxysmal ventricular tachycardia and multifocal ventricular premature complexes were observed by Holter 24-hour electrocardiography in all 3 patients. Two of the 3 patients did not receive corticosteroids, but remaining patient is on a regimen of corticosteroid.

Adult↗

A stable analogue of thromboxane A2, 9,11-epithio-11,12-methanothromboxane A2, stimulates bone resorption in vitro and osteoclast-like cell formation in mouse marrow culture.

Thromboxane A2 (TXA2) is a powerful promoter of platelet aggregation and smooth muscle contraction. However, this compound is highly unstable and is rapidly hydrated to a more stable metabolite, thromboxane B2 (TXB2). TXA2 has been considered to be involved in bone resorption, in particular bone loss caused by inflammatory diseases and by orthodontic treatment. However precise mechanisms of bone resorption caused by TXA2 have not yet been proved because of its highly unstable nature. Recently, a chemically stable analogue of TXA2, 9,11-epithio-11,12-methanothromboxane A2 (STA2), was successfully synthesized. Using this synthetic compound, we examined its in vitro bone resorbing activity and induction of osteoclast-like cells in a mouse marrow culture system in comparison with related compounds with bone resorbing activity. Like prostaglandin E2 (PGE2), a well-known bone resorbing agent, STA2 time- and dose-dependently stimulated the release of 45Ca from prelabelled mouse calvariae. Both STA2 and PGE2 induced the accumulation of cAMP in mouse calvariae. The TXA2 antagonist, ONO-3708, inhibited STA2-induced release of 45Ca. TXB2 induced neither bone resorption nor cAMP accumulation. When mouse marrow cells were cultured with STA2 for 8 days, osteoclast-like multinucleated cells appeared in parallel with the increase of the amount of STA2 added. Again TXB2 showed no effect on osteoclast-like cell formation. These results indicate a role for TXA2 in some form of bone resorption.

Animals↗

Effect of a continuously applied compressive pressure on mouse osteoblast-like cells (MC3T3-E1) in vitro.

Bone metabolism is often affected by a variety of mechanical forces, but the cytological basis of their action is not known. In this study, we examined the effect of a continuously applied compressive pressure (CCP) on the growth and differentiation of clonal mouse osteoblast-like cells (MC3T3-E1) cultured in a specifically devised culture chamber. The gas phase of the chamber was maintained at a pressure of 2 atmospheres (atm) above ambient (3 atm total, 3.1 kg/cm2; 3.0 x 10(5) Pa) by continuously infusing a compressed mixed gas (O2: N2:CO2 = 7.0%:91.3%:1.7%). The pO2, pCO2, and pH in the culture medium at 37 degrees C under 3 atm were maintained at the same levels as those under 1 atm. MC3T3-E1 cells were cultured in alpha-minimal essential medium containing 10% fetal bovine serum under either 3 atm in the CCP culture chamber or 1 atm in an ordinary CO2 incubator. Alkaline phosphatase activity, a marker of osteoblasts, was greatly suppressed by the CCP treatment. The inhibition of alkaline phosphatase activity was rapidly restored when the cells were transferred to an ordinary CO2 incubator under 1 atm, indicating that the inhibition of alkaline phosphatase activity by CCP is reversible. Cell growth was not altered under CCP. The CCP treatment greatly increased the production and secretion of prostaglandin E2 (PGE2). Adding either conditioned medium from the CCP culture or exogenous PGE2 to the control culture under 1 atm suppressed alkaline phosphatase activity dose-dependently. The CCP treatment also suppressed collagen synthesis and calcification. These results suggest that CCP causes the cells to produce and secrete PGE2, which, in turn, inhibits differentiation of osteoblasts and the concomitant calcification.

Animals↗