Search PubMed⌕ Search

Biomedical subjects

K Higashi

Publications and source records attributed to K Higashi.

At least 235 records · Page 13Linked to original sources

Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) in vitro in aplastic anemia and myelodysplastic syndrome.

Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was examined in vitro in 23 patients with aplastic anemia and 14 with myelodysplastic syndrome (MDS) to investigate the clinical use of rh-Ep for these diseases. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU-E and BFU-E assays. In normals, the CFU-E numbers reached a plateau of increase at Ep doses of almost 2-5 units, and no further increase was observed with the addition of larger Ep doses. In aplastic anemia, the responses of CFU-E to Ep were relatively good in nonsevere type and generally poor in severe type. However, the CFU-E numbers increased with increasing doses of Ep in some of the patients with aplastic anemia. Among the patients with MDS, the responses of CFU-E to Ep were relatively good in primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia. On the other hand, the responses of CFU-E to Ep were poor in refractory anemia with an excess of blasts (RAEB) and RAEB in transformation among the MDS patients. BFU-E responses to Ep were poor in severe aplastic anemia, RAEB, and RAEB-T. However, there are Ep responsive patients in some of aplastic anemia and PARA. High titers of rh-Ep were suggested to be effective clinically in some patients with aplastic anemia and those with PARA.

Anemia, Aplastic↗

Frequent rearrangement of chromosomal bands 1p22 and 11q13 in squamous cell carcinomas of the head and neck.

We report the finding of clonal structural chromosome abnormalities in short-term cultures from 15 squamous cell carcinomas of the head and neck region. When the distribution of chromosomal breakpoints in these 15 tumors and in the 16 head and neck carcinomas previously described are assessed, a marked clustering is seen at bands 1p22 and 11q13, which are rearranged in eight and nine tumors, respectively. No other band was involved in aberrations in more than five tumors. Cytogenetic evidence of gene amplification was seen in four tumors, three times in the form of homogeneously staining regions (twice located in 11q13), and in one tumor as double minutes. Among the candidate genes for such amplification are BCLI, INT2, and HSTI, all of which map to 11q13, and NRAS, which maps to 1p22. All these oncogenes have previously been shown to be amplified in subsets of head and neck carcinomas. We conclude that bands 1p22 and 11q13 are nonrandomly involved in chromosomal rearrangements in head and neck carcinomas and suggest that activation of oncogenes located in these bands may proceed via cytogenetic mechanisms.

Aged↗

Simultaneous activation of heat shock protein (hsp 70) and nucleolin genes during in vivo and in vitro prereplicative stages of rat hepatocytes.

Rapidly growing cells usually have high levels of ribosome biogenesis. The sequential expression of protooncogenes during the transition of quiescent hepatocytes to the replicative stage was assumed to be followed by activation of cellular genes related to cell growth such as ribosome biosynthesis. First, the expression of major nucleolar protein (nucleolin or C23) and major heat-shock protein (hsp 70) genes was examined during rat liver regeneration. hsp 70 may function in cell growth and has a characteristic nucleolar location after heat shock. Both nucleolin and hsp 70 mRNA began to increase simultaneously after peaks of c-fos and c-myc, showed a peak 6 h after partial hepatectomy, and declined to the control levels around 20 h. That is, the peaks of nucleolin and hsp 70 mRNA precede the peak of ribosome formation (12-20 h) and DNA replication (24 h). Second, the behavior of nucleolin and hsp 70 mRNA was examined in primary cultured hepatocytes during their G0-G1 transition. Although the amounts of c-myc mRNA reached a plateau around 20 h after the initiation of culture and remained at these levels, DNA synthesis has never been found to start without the addition of EGF and insulin to this system. Both nucleolin and hsp 70 mRNA began to increase at around 20 h (prereplicative stage) and simultaneously decreased in inverse proportion to DNA synthesis induced by these growth factors. Thus, it is possible that the simultaneous enhancement of nucleolin and hsp 70 genes as described above is not merely coincidental, but is important biologically during the transition of quiescent hepatocytes to proliferative cells.

Animals↗

Elastic anisotropy of bivalve hinge-ligament.

Compressive stress-strain properties of an elastic ligament of a bivalve, Pseudocardium sachalinensis were investigated in the swollen state in water. The ligament is a calcified tissue, composed of calcium carbonate and insoluble protein which is rich in methionine S-oxide residue [Kikuchi, Y. and Tamiya, N., J. Biochem. (Tokyo) 89, 1975-1976 (1981)]. X-ray diffraction study showed that calcium carbonate existed only in orthorhombic aragonite form, and that all the crystal c-axes of the unit cell orientate nearly in the growing direction of the ligament. The uniaxial compression modulus for the growing direction was appreciably larger than those for the other two directions, while the anisotropy of the modulus was absent for a decalcified ligament. Thus the mechanical anisotropy of the ligament could be explained by means of the uniaxially oriented structure of aragonite crystals being dispersed in a nearly isotropic protein matrix.

Animals↗

Different responses of cytosolic and mitochondrial glutathione in rat livers after ethylene oxide exposure.

Acute effects of ethylene oxide (EO) at the concentration of 500 and 1500 ppm on glutathione and glutathione reductase of the cytosol and mitochondria in rat liver were examined. The levels of reduced glutathione content and the glutathione reductase activity in the cytosol at 1500 ppm exposure decreased to approximately 10% and 60% of those of control rats, respectively. The decreases in glutathione content and glutathione reductase activity in the mitochondria were less significant than those in the cytosol. Both mitochondrial NADPH-cytochrome c reductase and cytochrome c oxidase activities were only slightly affected by these EO exposures. These results indicate that the change in glutathione content in the cytosol mainly occurred due to the response to EO exposure, and that the mitochondrial glutathione did not serve for such cellular function.

Administration, Inhalation↗

Resuscitation by extracorporeal lung assist of a patient suffocating after inhalation of sawdust particles.

A 17-yr-old male accidentally inhaled a massive amount of sawdust particles. Severe respiratory distress developed, resulting in subcutaneous emphysema and left pneumothorax. Therefore, sufficient positive-pressure ventilation was inapplicable. Under veno-venous extracorporeal lung assist (ECLA) with an artificial lung, the sawdust particles were removed by broncho-fibroscopy and lung lavage. After 36 h, the patient was weaned from ECLA without further complications.

Adolescent↗

Human herpesvirus 6 infection in renal transplantation.

The relationship between renal transplantation and human herpesvirus 6 (HHV-6) infection was studied. All 21 kidney donors examined had antibody to HHV-6 at the time of transplantation. The 21 kidney recipients also had detectable antibody to HHV-6 before transplantation--and, of these, 8 patients showed a significant increase of serum antibody titer against HHV-6 after transplantation. All these 8 recipients suffered severe kidney rejection. Furthermore, virus isolation from peripheral blood lymphocytes of 2 recipients who suffered rejection was attempted, and in both cases HHV-6 was isolated. Biopsy specimens of rejected kidneys of 9 other patients were examined for the presence of HHV-6 antigens, and in 5 of these specimens antigens were detected in the tubular epithelium, as well as in infiltrating histiocytes and lymphocytes. These results suggest that HHV-6 can infect renal tissues and that the infection may be correlated with rejection or with immunosuppressive therapy.

Adult↗

Local ofloxacin delivery using a controlled-release insert (PT-01) in the human periodontal pocket.

PT-01, a controlled-release insert, was developed for topical chemotherapy in periodontal disease. It is a soluble insert that consists of fast-release and sustained-release parts containing ofloxacin (OFLX) as an antibacterial agent. In this study, the release profile of OFLX from PT-01 was investigated in vitro. Twelve adult volunteers were administered OFLX as PT-01 or as an aqueous solution into their periodontal pockets, OFLX concentrations in gingival crevicular fluid (GCF) were evaluated from the viewpoint of pharmacokinetics. The in vitro release profile of OFLX from PT-01 showed a biphasic pattern. The release rate of OFLX was relatively rapid in the early phase and slow thereafter. When OFLX aqueous solution was administered into periodontal pockets, the OFLX level in GCF rapidly decreased to be about 1/100 after 30 minutes. When PT-01 was inserted into the pockets, the OFLX level in GCF immediately reached a peak (about 12 mg/ml), and gradually decreased until the 3rd day, and maintained a constant level above 2 micrograms/ml, the effective minimum antibacterial concentration for periodontopathic microorganisms, from the 3rd to 7th day after insertion. No side-effects were observed in the volunteers who received the PT-01 insert. The above results suggest that PT-01 is a suitable pharmaceutical preparation for periodontal chemotherapy.

Adult↗

Intracranial metastasis of a spinal cord astrocytoma--case report.

The authors report a case of cerebral metastasis from a spinal cord astrocytoma. The first metastatic tumor was controlled by radiation therapy. A second metastatic brain tumor was detected 2 years later, but attempts to control it through subtotal removal and chemotherapy failed. Metastasis from a spinal cord tumor to the brain is a rare event.

Astrocytoma↗

[Magnetic resonance imaging of subarachnoid hemorrhage due to ruptured intracranial aneurysm].

We report MRI (magnetic resonance imaging) findings of 31 cases with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm. Among these cases, 25 were studied within 72 hours after onset of SAH. A resistive type MRI scanner operating at a field of 0.2 Tesla was used in obtaining inversion recovery (IR) and saturation recovery (SR) images. IR 1500/43/400 (T1 weighted image, T1W), SR 1000/60 (SR image) and SR 2000/100 (T2 weighted image, T2W) were chosen for analysis. The SR image was usually adopted and coronal and/or sagittal images were added when there was enough time for examination. Slice thickness was 10 mm and slice interval was 15 mm. The scan was not necessarily aimed at the visualization of aneurysm itself. 1) In the acute phase of SAH, subarachnoid spaces near the ruptured aneurysm were appeared as isointensity areas on T1W and as high intensity areas on SR image. In the subacute phase, they were depicted as high intensity areas on both T1W and SR images, and as high intensity areas on T2W. 2) Intraventricular hemorrhage was visualized as a niveau-like high intensity area, especially, within the posterior horns on the SR images. 3) SR and T2W images were suitable for detection of aneurysm itself. In a resistive-type scanner, small aneurysms were not easily visualized due to the lack of high resolution. However, 29% of aneuysms, which were not giant, could be visualized on MRI. 4) Identification of intracerebral hemorrhage and cerebral ischemia from various causes was easy on both T1W and T2W images.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The experimental study for autoperfused heart-lung preservation--evaluation of pulmonary function after transplantation].

Although various methods for keeping long term good pulmonary function have so far been studied, no reliable method for heart-lung preservation has been established yet. Recently, we aimed at heart-lung preservation using the autoperfusion method and mainly examined pulmonary function after transplantation. After preserving heart-lung organ blocks extracted from mongrel dogs by autoperfusion method, 10 left lungs (preserved for 6.8 +/- 0.8 h) were orthotopically transplanted and combined heart-lung transplantation was performed under extracorporeal circulation using 5 heart-lung grafts (preserved for 7.5 +/- 0.5 h). All of lung-transplanted dogs were alive; preserved lungs showed good gas exchange power from immediately after transplantation. Left lungs on the 3rd day showed normal histological findings and chest X-P also revealed good pneumatization of transplanted lungs. The heart-lung transplantation enabled 4 cases to be free from extracorporeal circulation and arterial blood gas analysis also revealed good results [PO2 396.5 +/- 34.7 mmHg, PCO2 35.5 +/- 6.9 mmHg (FiO2 1.0)]. Lung tissue findings after 6 hours from the above freedom showed slight edema alone. The above results suggested the effectiveness of the autoperfusion method for heart-lung preservation.

Animals↗

Inverse correlation between N-myc amplification and catecholamine metabolism in children with advanced neuroblastoma.

The relationship between urinary excretion of catecholamine and/or its metabolites before the initiation of therapy and the genomic amplification of N-myc of the extirpated primary tumors was studied in 32 patients who had advanced neuroblastoma (stages III and IV). Values of vanillylmandelic acid, homovanillic acid, and noradrenaline excreted in urine were significantly higher in patients with 1 to 10 copies of N-myc (L-group) than in those patients who had more than 10 copies (H-group), whereas values of dopamine in urine were not significantly different between the groups. The ratio of urinary noradrenaline and dopamine was also significantly higher in the L-group. N-myc amplification, urinary excretion of vanillylmandelic acid and the noradrenaline/dopamine ratio significantly affected the prognosis. These data suggest that an inverse regulatory mechanism might be present between the N-myc amplification and catecholamine metabolism in patients who have advanced neuroblastoma, possibly at the level of gene and/or enzyme. These events would influence the prognosis. The main blockade of the metabolism may be in the metabolic processes from dopamine to noradrenaline.

Antineoplastic Combined Chemotherapy Protocols↗

Decreased activation of carcinogens in the liver of carcinogen-resistant rats.

We have developed a new strain of rats (resistant rat) which exhibit resistance against the carcinogenic action of several carcinogenic compounds. In the present study, we compared the ability of resistant rat liver to activate 3'-methyl-4-dimethylaminoazobenzene and 2-acetylaminofluorene to highly reactive metabolites, which can covalently bind to DNA, with that of carcinogen-sensitive parent strain rats (sensitive rat), using in vitro DNA binding assay. The covalent binding of these carcinogens to calf thymus DNA, catalyzed by the hepatic 9000 x g supernatant fraction from resistant rats pretreated with 3-methylcholanthrene, was about one-half of that catalyzed by the 9000 x g supernatant from sensitive rats which had received the same treatment. These results suggest that the ability of resistant rat liver to activate the carcinogens decreases compared to sensitive rat liver. Further experiments revealed that this decreased activation of the carcinogens in resistant rat livers is due to a low inducibility of 3-methylcholanthrene-inducible forms of cytochrome P-450 mRNA. The hepatic cytosolic Ah receptor concentrations in resistant rats were shown to be significantly lower than those of sensitive rats. Scatchard plot analysis demonstrated, however, that there is no significant difference between the affinity of Ah receptors for 2,3,7,8-tetrachlorodibenzo-p-dioxin in these two strains. These data implicate that the hepatic Ah receptor level may be an important factor in determining carcinogen sensitivity in rats.

2-Acetylaminofluorene↗

The solubility and colloidal behaviour of neptunium (IV).

The solubility and colloidal particle formation of Np(IV) in 10(-1) M Na2S2O4 solution in the pH range 2-10 were studied by sequential filtration with decreasing filter pore size. With the help of spectrophotometry and an extraction technique, the species remaining in the final filtrate were found to be Np(V) at pH less than 6 and Np(IV) at pH greater than 8; particle species were attributed to Np(IV). The solubility data obtained at pH less than 6 were interpreted using the reaction: Np(OH)4(am)----NpO2+ + e- + 2H2O, log K = -6.7 +/- 0.4 At pH greater than 8, the solubility increased rapidly with increasing pH in the presence of air, and this was interpreted as being due to the formation of the negatively charged species Np(CO3)4x - 2x. The formation constants beta 3 and beta 4 were estimated to be similar to those reported for Pu(IV). The size distribution of colloidal Np(IV) was also obtained. Some simple models used to describe the observed size distributions and to estimate the equilibrium size distributions of colloidal Np(IV) were examined.

Colloids↗

To-and-fro veno-venous extracorporeal lung assist for newborns with severe respiratory distress.

A veno-venous to-and-fro bypass method through a single blood access for extracorporeal lung assist with an artificial membrane lung is introduced. A premature newborn with severe respiratory distress was treated with this method. A 12 Fr. single lumen catheter with a spiral-embedded thin-wall, 0.25 mm in wall thickness, was placed in the right internal jugular vein. Venous blood was withdrawn and oxygenated blood returned alternately through the same catheter. Thus both carotid arteries and other large veins were kept intact. During the extracorporeal bypass, the patient was put on intermittent mandatory ventilation of 2 times/min for lung rest providing adequate arterial blood gases, and he survived.

Cardiopulmonary Bypass↗

Lipid peroxidation and the metabolism of glutathione in rat liver and brain following ethylene oxide inhalation.

The effects of repeated exposure to ethylene oxide on lipid peroxidation and glutathione metabolism in both rat liver and brain were examined. Increased levels of malondialdehyde (MDA) in the liver were observed after 6 and 13 weeks of exposure to ethylene oxide. The increased level of MDA observed in the hepatic homogenates of the treated rats reflected that of the microsomal fraction. On the other hand, no change in the level of MDA was detected in the brain of rats either at a 6- or 13-week treatment. Glutathione reductase activity was found to decrease at 6 or 13 weeks in liver and brain of treated rats. Both reduced and oxidized forms of glutathione in homogenates of liver and brain obtained from treated rats were, however, similar to those of the control at 40 h after the last exposure in individual experiments. To elucidate the cause of lipid peroxidation, the time course of glutathione content after exposure with ethylene oxide were studied in more detail. Significant decreases in both GSH and GSSG content in these organs were detected shortly after exposure to ethylene oxide and their levels recovered gradually with time and reached the control values at 40 h in the liver, although the changes were less significant in the brain as compared with those in the liver. These results suggest that enhancement of lipid peroxidation in the microsomal fraction of the liver after repeated exposure to ethylene oxide may possibly arise from repeated depletions of glutathione to certain critical levels and less removal of lipid peroxidation.

Administration, Inhalation↗