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Biomedical subjects

M Ueno

Publications and source records attributed to M Ueno.

At least 19 recordsLinked to original sources

Tumor necrosis factor and coagulopathy in patients with prostate cancer.

This study was undertaken to evaluate the relationship between serum tumor necrosis factor (TNF) and coagulopathy in patients with prostate cancer. TNF levels in 104 sera obtained from 101 prostate cancer patients were determined using an enzyme immunoassay. Serum levels of fibrin/fibrinogen degradation product E fragment (FDP) and plasma levels of fibrin degradation product D-dimer in patients with elevated serum TNF levels were 1221.95 +/- 375.94 ng/ml and 27.34 +/- 9.81 micrograms/ml, which were significantly higher than those (FDP, 94.35 +/- 13.17 ng/ml; D-dimer, 1.03 +/- 0.20 micrograms/ml) in patients with undetectable serum TNF levels (P < 0.01). In addition, patients with elevated serum TNF levels showed significant increases in plasma levels of thrombin-antithrombin-III complex and plasmin-alpha 2-antiplasmin inhibitor complex and a significantly higher incidence of positive plasma soluble fibrin monomer complex than did those with undetectable serum TNF levels. The percentage of prothrombin time was significantly decreased in the group with elevated serum levels of TNF. Serum levels of TNF were significantly elevated in patients with serum FDP levels of > or = 200 ng/ml than in those with serum FDP levels of < 200 ng/ml (3.91 +/- 0.45 versus 2.17 +/- 0.08 units/ml) and in patients with plasma D-dimer levels of > or = 2 micrograms/ml than in those with plasma D-dimer levels of < 2 micrograms/ml (3.82 +/- 0.48 versus 2.10 +/- 0.06 units/ml). These results suggest that TNF may be one of the pathogenetic factors that could explain the occurrence of coagulopathy in patients with prostate cancer.

Adenocarcinoma

Successful management of portal hypertension following artificial arterioportal shunting: report of a case.

A 63-year-old woman diagnosed as having hepatic hilar cancer underwent an extended left lobectomy of the liver with excision of the right hepatic artery which was involved by the tumor. Because the hepatic artery could not be reconstructed by direct anastomosis, an artificial arterioportal (A-P) shunt was constructed between the common hepatic artery and the portal vein. However, 4 weeks after the operation, portal hypertension with severe esophageal varices developed. Under the diagnosis of portal hypertension caused by excessive blood flow from the A-P shunt, coil embolization of the common hepatic artery was performed using an angiographic technique, following which the esophageal varices completely disappeared. This case demonstrates that portal hypertension after A-P shunting can be effectively treated with coil embolization.

Angiography

Immunocytochemical studies of protamine-induced blood-brain barrier opening to endogenous albumin.

The cellular mechanisms of blood-brain barrier (BBB) opening to endogenous albumin in the mouse brain after intracarotid infusion of solutions of protamine free base (PB) or protamine sulfate (PS) were studied using quantitative immunocytochemistry. Ultrathin sections of brain samples embedded at low temperature in Lowicryl K4M were exposed to anti-mouse albumin antiserum followed by protein A-gold. Using morphometry, the density of immunosignals (gold particles per micron2) was recorded over four compartments: vascular lumen, endothelial profiles, subendothelial space (including the basement membrane), and brain parenchyma (neuropil). In addition, the adsorption of endogenous albumin evidenced by the number of gold particles per micron of the endothelial luminal plasmalemma was quantitatively evaluated. In the applied experimental conditions, PB was found to be strongly cytotoxic as indicated by the appearance of rapid degenerative changes and the disruption of the endothelial lining with concomitant clumping of the blood plasma. The action of PS was milder, offering a better opportunity for detailed ultrastructural and morphometric examination of brain samples during consecutive steps of PS action (2, 5, 10 and 30 min). As early as 10 min after infusion of PS solution, the adsorption of blood plasma albumin to the endothelial luminal surface was increased 2.5 times. Simultaneously, the immunolabelling of the endothelial profiles and subendothelial space was significantly increased. These results suggest that BBB disruption occurs through enhanced adsorption of albumin or albumin-protamine complexes to the luminal plasmalemma, followed by transendothelial vesicular transport, rather than through modification of interendothelial junctional complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins

Low molecular weight immunomodulators produced by microorganisms.

In order to develop a new class of low molecular weight immunomodulators for the treatment of incurable diseases involving cancer, hematologic diseases and inflammation, we have sought cytokine inducers and inhibitors of cell adhesion to the extracellular matrix among the low molecular compounds produced by microorganisms. Cytogenin, cytoblastin (a monokine inducer), conagenin (a lymphokine inducer) and delaminomycins and IC-101 (inhibitors of cell adhesion to extracellular matrices) have been recently found in our institute. In this report, we describe the principles of screening and structures, and discuss their biological activities.

Actinobacteria

Sequence-specific DNA binding by covalently constrained peptide dimers of the basic leucine zipper protein GCN4.

DNA binding of covalently bonded peptide dimers was studied by using enantiomeric and C2-symmetric templates as a dimerization module. Amino acid sequence of the peptide is derived from that of DNA contact region of the basic leucine zipper protein GCN4. These peptide dimers were designed to possess different constraints with respect to the orientation of two peptides. The basic region peptides were covalently linked to the enantiomeric template at the C-terminal ends. Two peptides are arranged either in a right-handed or left-handed geometry depending on the chirality of the template. The GCN4 basic region dimers with both right-handed and left-handed geometries show equal affinity to the native GCN4 binding DNA sequences, 5'-ATGACTCAT-3' and 5'-ATGACGTCAT-3', as revealed by the gel mobility shift assay. Specific recognition of the palindromic DNA sequence by the peptide dimers was confirmed by the DNase I footprinting. Circular dichroism spectroscopic study indicates that the basic region peptides bound the target DNA sequence in a helical conformation. The degree to which a chiral constraint effects may depend on the geometry of two DNA binding domains in the parent protein-DNA complex and on a position to apply the chiral constraint.

Base Sequence

Preparation and characterization of dextran magnetite-incorporated thermosensitive liposomes: an on-line flow system for quantifying magnetic responsiveness.

PURPOSE: Dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), were prepared and characterized in order to investigate their possibility for magnetic drug targeting. METHODS: TMs containing calcein were prepared at various DM concentrations by reverse-phase evaporation of dipalmitoylphosphatidylcholine (DPPC). They were evaluated for their physicochemical properties including size, DM capture, magnetite distribution within liposomes, and temperature-dependent calcein release. Moreover, a novel on-line flow apparatus with a sample injector, a coil of tubing placed in an electromagnet, and a fluorescence detector was developed for quantifying the magnetic responsiveness of TMs. This device allowed us a real-time measurement of percentage holding of TMs by magnetic field. RESULTS: Due to water-soluble property of DM, higher contents of magnetite up to 490 mg per mmol DPPC were successfully incorporated into the liposomes with DM than with conventional magnetite (Fe3O4). Thermosensitivity and lipid integrity of TMs were not influenced by inclusion of DM. Using the on-line flow system, percentage holding of TMs by magnetic field was shown to vary with several factors; it increases as the magnetic field strength increases, the fluid flow rate decreases, the magnetite content increases, and the liposome concentration increases. Typically, at 490 mg incorporated magnetite per mmol DPPC, 0.5 ml/min-fluid flow rate, and high magnetic field strength (> or = 10 kiloGauss), approximately 100% of TMs were found to be held. CONCLUSIONS: The TMs were suggested to be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.

1,2-Dipalmitoylphosphatidylcholine

A novel 5-HT1-like receptor subtype mediates cAMP synthesis in porcine pial vein.

The 5-hydroxytryptamine (5-HT) receptor subtype mediating 5-HT inhibition of spontaneous rhythmic contractions (SRC) in the porcine pial vein was characterized. Results from pharmacological studies using in vitro tissue bath techniques indicated that the inhibitory effects of 5-HT on SRC were qualitatively and quantitatively mimicked by 5-HT1-like agonists 5-methoxytryptamine (5-MT) and 5-carboxamidotryptamine (5-CT). 5-HT-, 5-MT-, and 5-CT-induced inhibitions of SRC were attenuated in a concentration-dependent manner by methysergide, which yielded similar pA2 values against these three agonists, suggesting that 5-HT, 5-MT, and 5-CT act on the same 5-HT1-like receptors. 5-MT inhibition of SRC was not affected by blocking 5-HT2 (with ketanserin and spiperone), 5-HT3 (with MDL-72222 and ICS-205-930), or 5-HT4 (with ICS-205-930) receptors. Neither was 5-MT inhibition of SRC affected by blocking 5-HT1A (with propranolol and spiperone), 5-HT1B (with propranolol), or 5-HT1C (with ketanserin) receptors. Furthermore, 5-HT and 5-MT inhibitions of SRC were enhanced by cilostazol [a selective adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor] and were diminished by KT-5720 (a cAMP-dependent protein kinase inhibitor) but were not affected by M&B-22948 [a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor] or KT-5823 (a cGMP-dependent protein kinase inhibitor). Biochemical studies further demonstrated that 5-HT inhibition of SRC in porcine pial veins was accompanied by an increase in cAMP, but not cGMP, synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Study on hepatic artery chemoembolization using temperature-sensitive liposome or lipiodol emulsion.

As a novel method for the medical application of liposomes, we have tried hepatic artery chemoembolization using temperature-sensitive liposomes with hyperthermia for the treatment of hepatic tumors. In this study, the effect of temperature-sensitive liposomes was compared with that of Lipiodol emulsion, which has been used clinically. The temperature-sensitive liposomes, consisting of dipalmitoylphosphatidylcholine or Lipiodol emulsions entrapping doxorubicin, were administered into the hepatic artery of hepatic tumor-bearing rats via a cannula. Doxorubicin administered in a liposomal form showed a high accumulative property toward tumors, with heating, while that in the emulsion form showed a slow release property toward tumors. Not only was tumor growth inhibited, but also, an actual diminishing of the tumor was observed in each form. Side effects were also examined: an abnormal rise in GPT, or necrosis of the normal tissues in liver, which was often observed in hepatic artery chemoembolization using Lipiodol emulsion, was remarkably reduced in the liposomal chemoembolization.

Animals

An ultrastructural study of glomerular basement membrane in rheumatoid arthritis patients with urinary abnormalities.

We measured the thickness of the glomerular basement membrane (GBM) in 48 rheumatoid arthritis (RA) patients with proteinuria and/or hematuria and studied its relationship to clinical features of RA. Ten cases with minor glomerular abnormalities, renal cancer, donor of renal transplantation, were studied as controls. Secondary glomerular diseases and hereditary thin basement membrane disease (TBMD) were excluded. Mean GBM thickness was 289 +/- 74 nm (mean +/- SD) in RA patients, which was significantly thinner than that of control group (342 +/- 38 nm) (p < 0.01). Mean GBM thickness were 276 +/- 72 nm and 336 +/- 68 nm in RA patients with and without gold sodium thiomalate (GST) treatment, respectively (p < 0.05). Mean GBM thickness of RA patients without GST and controls were not different statistically, but RA patients with GST had significantly thinner GBM, compared with controls (p < 0.01). The mean thickness of GBM were also 274 +/- 69 nm and 344 +/- 72 nm in RA patients with and without hematuria, respectively (p < 0.01). According to these results, we suspect that the thinning of GBM in RA patients may be related to GST treatment.

Adolescent

[The renal tubulointerstitium in diabetes mellitus].

Recently, the tubulo-interstitial lesions in diabetes mellitus (DM) have become of greater interest, as well as, glomerulosclerosis. From the view points of tubular function, a variety of changes, including tubular proteinuria and transport of sodium, glucose, and divalent ions have been known until the present time, although the details remain to be elucidated. Morphologically the interstitial fibrosis and the thickening of tubular basement membrane were pointed out to be important features in incipient or overt diabetic nephropathy of insulin-dependent DM patients. We found the expansion of interstitium even in the area without hyalinized glomeruli and atrophic tubules in normo- and microalbuminuric non-insulin dependent DM patients by semiquantitative evaluation of biopsy specimens. Further studies of the mechanisms will be necessary to clarify the mechanism of the development of diabetic nephropathy.

Diabetic Nephropathies

Nephrotic syndrome in a bone marrow transplant recipient with chronic graft-versus-host disease.

A 21-year-old male developed massive proteinuria and microscopic hematuria, 1 year after allogeneic BMT for acute lymphoblastic leukemia. These symptoms occurred during an exacerbation of chronic cutaneous graft-versus-host disease (GVHD). Renal biopsy revealed granular deposits of IgG and IgM along the glomerular basement membrane, and subepithelial electron dense deposits. A diagnosis of membranous nephropathy was made. With prednisolone therapy proteinuria decreased gradually, and amelioration of cutaneous lesions was also noted. It was speculated that the disordered immune regulation of chronic GVHD resulted in the development of immune complex nephritis.

Adult

[Venovenous extracorporeal membrane oxygenation in an elderly patient with severe respiratory failure--report of a case].

A 69-year-old woman, who developed acute respiratory distress syndrome (ARDS) after coronary artery bypass grafting, underwent venovenous extracorporeal membrane oxygenation (V-V ECMO) because conventional ventilatory support was ineffective. We used a covalently bonded heparin surface ECMO system, including an artificial lung, a centrifugal pump, cannulas, tubing and connectors, that was maintained with low-dose systemic heparinization, the patient was weaned from ECMO after 186 hours. During ECMO, her platelet count was about half of the initial level and markedly elevated thrombin-antithrombin complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and D-dimer were decreased by the use of heparin and protease inhibitors. V-V ECMO seems to be useful even in patients with severe adult respiratory failure and can be performed safely if a heparin covalent circuit is applied.

Aged

Activation of protein kinase C and the involvement of prostaglandin E2 in the inhibition of osteosarcoma-derived cell alkaline phosphatase activity.

We present evidence for the presence of specific, high-affinity binding sites for tritiated phorbol 12,13-dibutyrate on osteosarcoma-derived (HT-3) cells. Activation of protein kinase C by a phorbol ester resulted in an inhibition of alkaline phosphatase activity and the accumulation of prostaglandin E2. Indomethacin blocked prostaglandin E2 production and enhanced alkaline phosphatase activity. These data suggest that prostaglandin E2 is enhanced by activation of protein kinase C, and in turn, alkaline phosphatase activity is reduced.

Alkaline Phosphatase

Isolation and characterization of CAJ1, a novel yeast homolog of dnaJ.

A novel member of the Escherichia coli dnaJ family, designated CAJ1, was isolated from a yeast expression library using antiserum against a yeast calmodulin-binding fraction. Although CAJ1 contains neither a Gly-rich region nor a Cys-rich repeat, as are found in other DnaJ relatives, it contains a leucine zipper-like motif.

Amino Acid Sequence

Potentiation of antigen-induced histamine release from rat peritoneal mast cells through a direct interaction between mast cells and non-mast cells.

Rat peritoneal mast cells, which had been sensitized two days earlier by an intraperitoneal injection of rat monoclonal IgE antibodies, were purified by density gradient centrifugation with 60% Percoll (cell purity > 95%). Histamine release from the purified mast cells (PMC) was then compared to that of a non-purified preparation (peritoneal exudate cells; PEC). Both PEC and PMC released similar amounts of histamine upon stimulation with calcium ionophore A23187 and compound 48/80. In contrast, antigen-induced histamine release from PMC was very low compared to that of PEC. PEC released up to 30% of total histamine upon challenge with 1 microgram/ml of antigen, whereas histamine release from PMC was only one third or less than that of PEC. When PEC was suspended in 60% Percoll and treated for a period needed for purification, the reduction of antigen-induced histamine release was negligible. Mast cells purified by centrifugation on a metrizamide gradient released only small amount of histamine similar to Percoll-purified mast cells. Non-mast cells (NMC) recovered from the interface of the 60% Percoll potentiated the antigen-induced histamine release from PMC concentration- and time-dependently. The supernatant of the NMC suspension which was incubated at 37 degrees C for 60 min, however, failed to potentiate histamine release in PMC. We concluded therefore that separation media such as Percoll and metrizamide do not cause the low antigen-induced histamine release in PMC, but that the separation of mast cells from other cells present in the peritoneal cavity itself causes it. Antigen-induced mast cell histamine release is potentiated through a direct interaction between mast cells and NMC, and some cell surface molecules also seem to be involved.

Animals

Cerebral pial arterial innervation with special reference to GABAergic innervation.

Glutamic acid decarboxylase (GAD)-immunoreactive (I) nerve fibers were observed to run parallel to other autonomic nerve fibers, especially vasoactive intestinal polypeptide (VIP)- and calcitonin gene-related peptide (CGRP)-I nerve fibers at the light microscopic level. At the ultrastructural level, GAD-immunoreactivities co-localized with CGRP immunoreactivities in nerve terminals, but not with choline acetyltransferase, VIP, tyrosine hydroxylase and neuropeptide Y immunoreactivities. GAD immunoreactivities were observed in the trigeminal ganglion, some of which were co-localized with CGRP-immunoreactivities. In the proximal portion of the internal carotid artery, GAD-I adventitial ganglion cells were observed and some were also immunoreactive for CGRP. These results strongly suggest that the origin of GABAergic innervation of the major cerebral pial arteries of the cat is mainly in the trigeminal ganglion, and partly in the adventitial ganglia of the internal carotid artery.

Animals

Early assessment of reperfusion therapy using cardiac troponin T.

OBJECTIVES: The purpose of this study was to investigate the utility of cardiac troponin T for early assessment of reperfusion therapy. BACKGROUND: Several biochemical markers are used for early noninvasive detection of reperfusion during intravenous thrombolytic therapy. However, cardiac troponin T, a new myocardial-specific marker, has not been used previously for this purpose. METHODS: We measured troponin T and creatine kinase, MB isoenzyme (CK-MB) levels in 38 patients with acute myocardial infarction whose infarct-related artery was totally occluded before reperfusion therapy. Subjects comprised 14 patients with successful angioplasty (group 1), 12 patients with successful thrombolytic therapy (group 2) and 12 patients with unsuccessful attempted reperfusion (group 3). Blood samples were taken every 15 min, and coronary angiography was performed every 5 to 8 min until 60 min after reperfusion (groups 1 and 2) or after the initiation of treatment (group 3). We calculated the increase in troponin T (delta troponin T) and CK-MB (delta CK-MB) 60 min after treatment was initiated and 60 min after reperfusion in groups 1 and 2. RESULTS: Mean (+/- SD) delta troponin T and delta CK-MB levels were 9.35 +/- 7.83 ng/ml and 125 +/- 83 mU/ml in group 1 and 3.23 +/- 3.08 ng/ml and 130 +/- 137 mU/ml in group 2, respectively, 60 min after treatment and were 10.1 +/- 8.35 ng/ml and 131 +/- 84 mU/ml in group 1 and 6.84 +/- 8.30 ng/ml and 158 +/- 146 mU/ml in group 2, respectively, 60 min after reperfusion. These values were significantly higher than those 60 min after treatment in group 3: 0.16 +/- 0.19 ng/ml and 10 +/- 9 mU/ml, respectively. The predictive accuracy for detecting reperfusion using a threshold value of 0.50 ng/ml of delta troponin T and 25 mU/ml of delta CK-MB was 100% in group 1 and 92% in group 2 60 min after treatment, respectively. There was significant correlation between delta troponin T and delta CK-MB. CONCLUSIONS: Serial measurements of cardiac troponin T as well as of CK-MB are useful for early assessment of reperfusion therapy.

Aged