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Biomedical subjects

Y Ohta

Publications and source records attributed to Y Ohta.

At least 721 records · Page 40Linked to original sources
PubMed1990

A new hematopoietic cell line, KMT-2, having human interleukin-3 receptors.

A novel human cell line, KMT-2, from umbilical cord blood cells was established based on the selection of cultures in the presence of recombinant human interleukin-3 (IL-3) and the sorting of cells with anti-My 10 antibody. Morphologic and cytochemical studies (peroxidase negative, Sudan-black negative, chloroacetate esterase negative, PAS positive, nonspecific esterase positive) and phenotyping (HLA-DR, My7 = CD13, My9 = CD33, My10 = CD34, MCS-2, LeuM1 positive, glycophorin A negative, and P2 negative) suggest that the KMT-2 cells are myelomonocytic cells, probably of immature progenitor origin. Besides IL-3, granulocyte-macrophage colony-stimulating factor supported the growth of the KMT-2 cells, but IL-1 alpha, IL-2, IL-4, IL-5, and erythropoietin did not. IL-6 showed only slight activity. Binding studies with 125I-labeled recombinant human (rh) IL-3 indicated that IL-3 bound to a single class of high affinity receptors (approximately 4,000 receptors/cell) on KMT-2 cells with a kd of approximately 200 pmol/L. The chemical cross-linking assay demonstrated that radiolabeled hIL-3 bound three molecules with molecular masses of 170, 130, and 70 Kd. Present data suggest that the newly established human cell line will be a valuable tool for the biologic assay of hIL-3, and a model for biochemical studies of IL-3 receptors.

Blood Cells↗
PubMed1990

Ca2+/calmodulin-dependent protein kinase II immunoreactivity in the rat hippocampus after forebrain ischemia.

The influence of transient forebrain ischemia on the temporal alteration of Ca2+/calmodulin-dependent kinase II (CaM kinase II) in the rat hippocampus was analysed by the immunohistochemical method using antigen-affinity purified polyclonal antibodies against CaM kinase II of rat brain. Six to twenty-four hours after ischemia, CA1 and CA3 pyramidal cells, and dentate granule cells lost CaM kinase II immunoreactivity in neuronal perikarya, although immunoreactivity in the dendritic fields was preserved. The recovery of immunoreactivity of the CA3 pyramidal cells and dentate granule cells was noted 3 days after recirculation. Seven days after ischemia, immunoreactivity in the CA1 subfield was greatly reduced. These results suggest that CaM kinase II molecules in the CA1 subfield are preferentially located on the CA1 pyramidal cells and that CaM kinase II plays a critical role in the reconstruction of neuronal cytoskeleton and neuronal networks damaged by ischemic insult.

Animals↗
PubMed1990

Organization of the six motor nuclei innervating the ocular muscles in lamprey.

The topography of motoneurons supplying each of the six ocular muscles of the lamprey, Lampetra fluviatilis, was studied by selective application of HRP to the cut nerves of identified muscles. In addition, the distributions of motoneuron populations to both eyes were studied simultaneously with fluorescein and rhodamine coupled dextran-amines (FDA and RDA) applied to cut ocular muscle nerves of either side. The motoneuron pool of the caudal oblique muscle is represented bilaterally in the trochlear (N IV) motor nucleus. The dorsal rectus muscle is innervated from a contralateral group of oculomotor (N III) motoneurons and the remaining four muscles exclusively from the ipsilateral side (N III and N VI). The inferior and posterior rectus muscles are both innervated by the abducens nerve. In contrast to all jawed vertebrates, only three eye muscles (the dorsal rectus, rostral rectus, and rostral oblique) are innervated by the oculomotor nerve in lampreys (N III). Lampreys have a motor nucleus similar to the accessory abducens nucleus previously described only in tetrapods. They lack the muscle homologous to the nasal rectus muscle of elasmobranchs and the medial rectus muscle of osteognathostomes. The distribution of the dendrites of different groups of motoneurons was studied and is considered in relation to inputs from tectum and the different cranial nerves.

Animals↗
PubMed1990

Sneeze-evoking region within the brainstem.

The neuronal mechanisms of sneezing were examined in precollicular-postmammillary decerebrate cats. Mechanical stimulation (frequency 20 Hz, peak-to-peak displacement 0.5 mm) of the nasal membrane evoked a series of sneezes. In the same preparation, electrical stimulation (duration 0.2 ms, frequency 10 Hz, 5-50 microA) delivered to the lower brainstem also evoked sneezes. The changes in EMG activity and subglottic pressure during brainstem-induced sneeze were similar to those recorded nasal-induced sneeze. The sneeze-evoking region was located along the ventromedial part of the spinal trigeminal nucleus and the adjacent pontine-medullary lateral reticular formation, and extended rostrocaudally from P4.0 to P14.5 according to the Horsley-Clarke coordinates. These results suggest that the sneeze-evoking region is a distinct structure of the brainstem, having a homogeneous function. This region appears to control the epipharyngeal, intrinsic laryngeal and respiratory muscles. The integrated activity of these muscles underlies the generation of a sneeze.

Abdominal Muscles↗
PubMed1990

Effects of subchronic treatment with natural human interferons on antipyrine clearance and liver function in patients with chronic hepatitis.

To determine whether natural human interferon administered under the usual therapeutic dosing scheme would inhibit the hepatic drug metabolism, we performed an antipyrine test in eight patients with chronic B or non-A, non-B hepatitis before and after a subchronic interferon therapy (6 megaunits/day for 17 +/- 4 days, mean +/- SD). Six patients received interferon-beta and 2 received interferon-alpha. To circumvent a possible influence of interferon-induced fever on the hepatic drug metabolism, the antipyrine test during the interferon therapy was performed at least 14 days after the interferon-induced fever disappeared. The kinetic parameters of antipyrine were obtained from seven saliva samples over 32 hours postdose. There were no significant differences in any kinetic parameters of antipyrine observed before and during the interferon therapy. With the sample size of the study, there was only a 20% chance (i.e., beta-power = 0.8 at alpha = 0.05) that we might have missed a 17% reduction in antipyrine clearance by the interferon therapy (type II error). On the other hand, the subchronic interferon therapy lowered serum aminotransferases and DNA polymerase activity significantly (P less than .05) compared with the respective baseline values. Our results suggest that the subchronic therapeutic dosing scheme of interferon as conducted in the present study does not cause the inhibitory effect on the oxidative drug metabolism to a statistically significant or clinically relevant degree in patients with chronic hepatitis, while it improves their liver function. Further studies are required for determining if different types of interferons administered under the different dosing schemes would alter the hepatic drug metabolism and the inhibitory effect would be time-dependent.

Adult↗
PubMed1990

A 1-year time course study of the relaxation times and histology for irradiated rat lungs.

To investigate the NMR relaxation times for irradiated rat lung tissue, we measured T1 and T2 at 11 different times during the injury's 1-year time course. A biexponential analysis of T2 was used to determine T2 fast (T2f) and T2 slow (T2s). In addition, we measured water content and correlated changes in the relaxation times with pathological changes. The correlation indicates the following: (1) Shortly after irradiation, the biexponential T2 decay for 1/3 of the samples became monoexponential and there were no noticeable pathological changes observed using light microscopy. (2) During radiation pneumonitis, T2f and T2s were prolonged. This accompanied acute edematous changes and inflammatory cell infiltration. (3) Finally, during radiation fibrosis T1 shortened and collagen increased. We observed no significant correlation between relaxation time changes and water content changes throughout the 1-year time course.

Animals↗
PubMed1990

T2 of endotoxin lung injury with and without methylprednisolone treatment.

NMR relaxation times (T1 and T2) and the water content (WC) of in vitro rat lungs were measured during the course of endotoxin lung injury in rats. Measurements of normal lungs, untreated endotoxin-injured lungs, and endotoxin-injured lungs treated with methylprednisolone (MPSL) were compared. The untreated endotoxin lungs showed prolongation of the fast and slow T2 components (T2f and T2s), but no significant changes in T1 or water content. Also, there was no correlation between 1/WC and relaxation rates or between T1 and T2. MPSL treatment prevented T2f and T2s prolongation; however, the duration of MPSL effectiveness was limited. Animals which were treated with MPSL more than 7 h prior to measurements showed T2 prolongation. This study indicates that NMR relaxation times, particularly T2, can be useful in evaluating lung injuries and their treatments.

Animals↗
PubMed1990

Quantitative analysis of antiatherosclerotic effect of nifedipine in cholesterol-fed rabbits.

Reports concerning the effect of slow calcium-channel blockers on experimental atherosclerosis are controversial. We examined the antiatherosclerotic effect of nifedipine (40 mg/day for 16 weeks) on aorta of rabbits on diets containing 0.3%, 0.5%, and 1.0% cholesterol. There were no significant differences in levels of serum lipids with or without nifedipine in the same cholesterol-fed rabbits. The results obtained show that nifedipine suppressed the extent of lipid deposition and surface involvement (S.I.) in aorta in 0.3% cholesterol-fed rabbits, whereas nifedipine only tended to suppress S.I. in 0.5% cholesterol-fed rabbits and had no effect in 1.0% cholesterol-fed rabbits. The log dose-response relationship of S.I. was obtained by plotting the concentration of cholesterol in the feed or the "integrated value" of the total serum cholesterol (TC), i.e., the cumulative sum of the serum TC values obtained at each week. The log dose-response curve was shifted in parallel with the right in nifedipine groups. The Lineweaver-Burk plot constructed from the dose-response curve had the same points crossing the ordinate with or without nifedipine. These results suggested that nifedipine suppressed S.I. in a competitive manner with cholesterol on the specific binding site of lipid deposition. Electron-microscopic findings also demonstrated that fat droplets in smooth muscle cells, extracellular matrix containing collagen, and elastic fibers decreased in nifedipine-treated rabbits.

Animals↗
PubMed1990

A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis.

A multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600 mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA-treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebo-treated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentration showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.

Alanine Transaminase↗
PubMed1990

Provocation of massive hepatic necrosis by endotoxin after partial hepatectomy in rats.

When rats received endotoxin 48 hours after two-thirds liver resection, 50% of them died within 12 hours with massive hepatic necrosis at a dose that did not affect sham-operated rats. In the hepatic sinusoids, fibrin deposition and endothelial cell destruction occurred 5 hours after endotoxin administration. When antithrombin III concentrate was infused concomitantly with endotoxin administration, all rats survived 12 hours, and the extent of hepatic necrosis and the deranged serum glutamic pyruvic transaminase values were significantly attenuated at 5 hours compared with those in the control rats. Similar improvements in the incidence of mortality and liver injury were observed after treatment with gum arabic before hepatectomy. The stimulatory state of Kupffer cells based on the ability to produce superoxide anions estimated by formazan deposition after liver perfusion with nitro blue tetrazolium and phorbol myristate acetate was increased between 24 and 72 hours after operation. This increase disappeared after gum arabic treatment. It is concluded that massive hepatic necrosis can occur as a result of sinusoidal fibrin deposition provoked by endotoxin in partially hepatectomized rats. Activated Kupffer cells may contribute to this provocation.

Animals↗
PubMed1990

Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions.

Serum alpha-fetoprotein from 146 patients with hepatocellular carcinoma, other malignancies, and benign liver diseases, was fractionated by lectin-affinity electrophoresis coupled with our sensitive detection method of antibody-affinity blotting. Compared with chronic hepatitis and liver cirrhosis, hepatocellular carcinoma was characterized by the increase in proportions of lentil lectin A-reactive alpha-fetoprotein-L3 and erythroagglutinating phytohemagglutinin-reactive alpha-fetoprotein-P4; the yolk sac tumor was characterized by the increase of concanavalin A-nonreactive alpha-fetoprotein-C1, lentil lectin-A-weakly reactive alpha-fetoprotein-L2, erythroagglutinating phytohemagglutinin-strongly reactive alpha-fetoprotein-P5, and Allomyrina dichotoma lectin-nonreactive, slow-migrating alpha-fetoprotein-Als; and gastrointestinal tumors were characterized by alpha-fetoprotein-C1, alpha-fetoprotein-L2, alpha-fetoprotein-L3, alpha-fetoprotein-P5 and Allomyrina dichotoma-nonreactive alpha-fetoprotein-A1. By combined evaluation of alpha-fetoprotein-L3 and alpha-fetoprotein-P4, hepatocellular carcinoma was discriminated from chronic hepatitis and liver cirrhosis with a sensitivity of 97% at a specificity of 99.7%. Because the alpha-fetoprotein level of the studied cases ranged from 60-1,500,000 ng/mL (60-1,500,000 micrograms/L), mostly greater than 200 ng/mL (200 micrograms/L), additional patients with lower levels of alpha-fetoprotein [16-177 ng/mL (16-177 micrograms/L) for 16 cases of hepatocellular carcinoma with liver cirrhosis and 28-185 ng/mL (28-185 micrograms/L) for 17 cases of liver cirrhosis alone] were analyzed for alpha-fetoprotein-L3 and alpha-fetoprotein-P4. The resulting sensitivity for combined evaluation was still as high as 88% at the same high specificity of 99.7%, indicating that the simultaneous analysis of alpha-fetoprotein-L3 and alpha-fetoprotein-P4 is effective in monitoring the evolution of hepatocellular carcinoma in cirrhotic patients.

Adult↗
PubMed1990

In vitro metabolism of testosterone on hepatic tissue of chicken (Gallus domesticus).

Among the subcellular fractions of chicken liver homogenates, the microsomal and cytosol fractions were most active in metabolism of testosterone with mutually different enzymological features. On the other hand, the nuclear and mitochondrial fractions had far lower activity of metabolizing the steroid. Metabolism by the cytosol fraction: the following steroids were identified as the metabolites of testosterone. 5 beta-Dihydrotestosterone (17 beta-hydroxy-5 beta-androstan-3-one), 5 beta-androstane-3 alpha,17 beta-diol and its 3 beta-epimer, 3 alpha-hydroxy-5 beta-androstan-17-one and its 3 beta-epimer and 5 beta-androstanedione. Metabolism by the microsomal fraction: from testosterone under aerobic condition, androstenedione was obtained as the major metabolite, besides the minor polar metabolites, production of which diminished when incubated in the atmosphere of carbon monoxide. From the results, testosterone was accepted to be firstly converted by the cytosol fraction into 5 beta-dihydrotestosterone which was then reduced to 5 beta-androstane-3 alpha,17 beta-diol and its 3 beta-epimer. These diols were further converted partially to 3 alpha -and 3 beta-hydroxy-5 beta-androstan-17-ones. These pathways were supported by the results of our incubation study with 5 beta-dihydrotestosterone and 5 beta-androstanedione as substrates. By the microsomes, testosterone was aerobically and anaerobically transformed to androstenedione as the major metabolite. Throughout our incubation experiments, no 5 alpha-reduction of a delta 4-3-oxo-steroid was detected in the chicken liver.

Animals↗
PubMed1990

Immunohistochemical study of human placental stromal cells.

An immunohistochemical study of stromal cells in human placental villi was made using various polyclonal and monoclonal antibodies. This study demonstrated that almost all villous stromal cells expressed HLA-ABC, which is indicative of class I major histocompatibility complex, and vimentin, which is a mesenchymal marker, through the entire period of pregnancy. Some of these stromal cells were considered to be fetal macrophages having HLA-DR, which is a determinant of class II major histocompatibility complex, particularly in the second and third trimesters. Such macrophages also expressed CD-4 (Leu-3a and -3b) and 2H4, which are the cell membrane determinants of suppressor-inducer T lymphocyte; CD-2 (Leu-5b), which is a marker of pan-T cell; Leu-M3, Leu-M5 and Mac-1, which are the markers of monocyte and macrophage lineage; leukocyte common antigen, which is a marker of bone marrow derived cell; and alpha-antichymotrypsin, which is a glycoprotein associated with macrophages. Morphologically, villous macrophages consisted of heterogeneous phenotypes such as classic Hofbauer cells, fibroblast-like spindle cells with long cytoplasmic processes, and dendritic-shaped cells. These may have more complex features than previously considered and may have a greater initiating role in immunologic interactions between mother and fetus when compared with the very sparsely distributed T or B lymphocytes.

Antigens, Differentiation↗
PubMed1990

Ca2+/calmodulin-dependent protein kinase II: localization in the interphase nucleus and the mitotic apparatus of mammalian cells.

Indirect immunofluorescence was used to determine the distribution of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in rat embryo fibroblast 3Y1 cells, rat C6 glioma cells, and human epidermoid carcinoma KB cells. During interphase at growing phase, CaM kinase II was localized diffusely in the cytoplasm and in the nucleus. In the nucleus, the enzyme was localized within the whole nuclear matrix in which the enzyme was specially concentrated in nucleoli. During mitosis, CaM kinase II was found to be a dynamic component of the mitotic apparatus, particularly present at microtubule-organizing centers. In metaphase and anaphase, CaM kinase II was observed at centrosomes and between the spindle poles. During telophase, CaM kinase II was condensed as a bright fluorescent dot at the midzone of the intercellular bridge between two daughter cells, while tubulin was found at each side of the midbody. Colchicine, a microtubule inhibitor, disorganized the tubulin- and CaM kinase II specific fluorescent structure of mitotic 3Y1 cells. In cold-treated cells, CaM kinase II was localized predominantly at centrosomes. The localization of CaM kinase II in the cell nucleus and the mitotic apparatus suggests that the enzyme may play a role in the cell cycle progression of mammalian cells.

Animals↗
PubMed1990

Hepatitis C virus infection is associated with the development of hepatocellular carcinoma.

A possible causative role for the recently discovered hepatitis C virus (HCV) in the development of hepatocellular carcinoma (HCC) was investigated by assay of sera from HCC patients in Japan for antibodies to a recombinant HCV antigen and to hepatitis B virus (HBV) antigens. Among the 253 HCC patients examined, 156 (61.7%) had no serum markers of either a previous or a current HBV infection (group I), 46 (18.2%) were negative for HBV surface antigen but positive for anti-HBV surface and/or anti-HBV core antibody, indicating the occurrence of a previous, transient HBV infection (group II), and 51 (20.2%) were chronically infected HBV carriers as evidenced by positivity for HBV surface antigen (group III). The prevalence of HCV antibody in group I (68.6%) and II (58.7%) patients was significantly higher than for group III (3.9%) or in 148 additional patients with other (non-HCC) cancers (10.1%) (P less than 0.01). Thus, there appears to be a strong association between HCV infection and the development of HCC, particularly in patients for which HBV infection cannot be implicated as a causative factor. The data also suggest an additional mode of transmission for HCV other than blood transfusion, since a history of blood transfusion was shown in only about 30% of the HCV antibody-positive HCC patients in groups I and II. A high prevalence of HCV antibody was also shown among patients with HCC whose disease was originally thought to be due to very high ethanol consumption.

Blood Transfusion↗
PubMed1990

Conversion of cholesterol to pregnenolone mobilizes cytochrome P-450 in the inner membrane of adrenocortical mitochondria: protein rotation study.

Rotation of cytochrome P-450 was examined in bovine adrenocortical mitochondria before and after an enzymatic transformation of cholesterol into pregnenolone by cytochrome P-450scc in the presence of malate. Rotational diffusion was measured by observing the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane normal" model. The measurements were used to investigate substrate-dependent intermolecular interactions of cytochrome P-450 with other redox components. Rotational mobility of cytochrome P-450 was significantly dependent on the decrease in cholesterol content by side chain cleavage reaction catalyzed by cytochrome P-450scc. In a typical experiment, the observed value for the normalized time-independent anisotropy r(infinity)/r(0) was decreased from 0.78 in control mitochondria to 0.60 after conversion of 21% of cholesterol to pregnenolone, while no significant change was observed for the average rotational relaxation time phi of about 700 microseconds. Significantly high values of r(infinity)/r(0) = 0.78 and 0.60 imply co-existence of mobile and immobile populations of cytochrome P-450. Since we observed that the heme angle tilted 55 degrees from membrane plane, 22% (control mitochondria) and 40% (after conversion of cholesterol to pregnenolone) of cytochrome P-450 in mitochondria are calculated to be mobile in the preparation. The significant mobilization of cytochrome P-450scc molecules caused by the conversion of cholesterol to pregnenolone is likely due to changes in protein-protein interactions with its redox partners, since the lipid fluidity was kept unchanged by the cholesterol depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗