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Biomedical subjects

N Aoki

Publications and source records attributed to N Aoki.

At least 397 records · Page 22Linked to original sources
PubMed1990

Lumboperitoneal shunt: clinical applications, complications, and comparison with ventriculoperitoneal shunt.

Lumboperitoneal (LP) shunting has the advantage of completely extracranial surgical management, minimizing intracranial complications. An LP shunt has been intentionally adopted for patients who require cerebrospinal fluid diversion. A retrospective study was designed to examine the indications for and complications associated with LP shunts in 207 patients (including 28 pediatric patients) treated during the past 11 years. Follow-up averaging 5.1 years revealed no deaths related directly to LP shunt placement. Twenty-nine patients (14%) underwent revision of the shunt because of obstruction. Shunt-related infections were observed in only 2 patients (1%). Radicular pain occurred in 10 patients (5%), 2 of whom required shunt replacement. Postoperative occurrence of dyspnea and disturbance of consciousness necessitated conversion to a ventriculoperitoneal (VP) shunt in 2 patients (1%), who subsequently were noted to have Chiari malformations. In 4 patients (2%), an acute subdural hematoma developed after mild head trauma. Symptomatic chronic subdural hematomas were observed in 2 patients (1%). One patient had a mild myelopathy that rapidly resolved after shunt replacement. The comparison to 120 patients treated with a VP shunt during the identical period (an average follow-up of 5.2 years) suggests the following conclusions. After subarachnoid hemorrhage caused by a ruptured aneurysm, hydrocephalus is usually of the communicating type and is an indication for an LP shunt. The incidence of infection and malfunction with an LP shunt is significantly lower than that with a VP shunt. An LP shunt is also indicated for pediatric patients, although a relatively higher incidence of malfunction is noted compared to adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Hereditary alpha 2-plasmin inhibitor deficiency caused by a transport-deficient mutation (alpha 2-PI-Okinawa). Deletion of Glu137 by a trinucleotide deletion blocks intracellular transport.

alpha 2-Plasmin inhibitor is the most important physiological inhibitor of fibrinolysis; hence, its deficiency results in a severe hemorrhagic diathesis. We have cloned and characterized a mutant alpha 2-plasmin inhibitor gene from an individual homozygous for the deficiency. By sequencing all the coding exons and exon-intron boundaries of the gene, a trinucleotide deletion in exon VII that results in deletion of Glu137 was identified. We have designated this variant as alpha 2-plasmin inhibitor Okinawa. Using DNA samples amplified with the polymerase chain reaction, hybridization analysis by oligonucleotide probes confirmed the presence of this mutation in all the affected family members, including both parents. To elucidate the mechanism by which this mutation leads to the deficiency, a eukaryotic expression plasmid for alpha 2-plasmin inhibitor containing this mutation was constructed and transfected into COS-7 cells for transient expression analysis. Immunoprecipitation analysis and enzyme-linked immunosorbent assay revealed that the mutant alpha 2-plasmin inhibitor synthesized is mostly retained within the cells as an endoglycosidase H-sensitive form, and only a small portion of it is secreted into the medium as a neuraminidase-sensitive form. These results suggest that the Glu137 deletion leads to the alpha 2-plasmin inhibitor deficiency by causing a block in its intracellular transport from the endoplasmic reticulum to the Golgi complex.

Animals↗
PubMed1989

Antiproliferative and differentiative effect of granulocyte-macrophage colony-stimulating factor on a variant human small cell lung cancer cell line.

A variant clone was adopted during passages of a small cell lung cancer cell line, GKT3-1.3. The variant clone exhibited distinct characteristics with alterations in morphology, positive staining with nonspecific esterase stain, and an increase in surface specific markers OKM5, HLA-DR, Mo1, and My7, usually found on monocytes or their precursors. However, it exerted a very rapid proliferation just like immature cells. This new clone, GKT3-1.3V, was shown to have specific binding capacity to granulocyte-macrophage colony-stimulating factor (GM-CSF), with a number of binding sites comparable to that of myelomonocytes or monocytic cell lines. Thus its proliferation was inhibited by GM-CSF in clonogenic assay and suspension culture. Increase in the percentage of cells with surface marker Mo1 by the addition of GM-CSF suggested its differentiative effect. Cell cycle analysis showed that the antiproliferative effect of GM-CSF was due to a block in G0 or G1. The antiproliferative effect of GM-CSF was abolished by the addition of anti-GM-CSF antibody.

Carcinoma, Small Cell↗
PubMed1989

Beneficial effects of a specific leukotriene receptor antagonist in splanchnic artery occlusion shock.

The purpose of this study was to examine the effects of a new potent peptidoleukotriene receptor antagonist, SK&F 104353, in splanchnic artery occlusion shock. SK&F 104353 was administered as a 1 mg/kg initial bolus followed by an infusion of 3 mg/kg per h for the entire 2 h post-reperfusion observation period. In a group of conscious rats, this dose of SK&F 104353 shifted the LTD4 dose response curve rightward 10-fold, indicating effective antagonism of peptidoleukotriene responses in the rat. Anesthetized rats subjected to splanchnic artery occlusion shock survived an average of only 98 +/- 8 min whereas all animals receiving SK&F 104353 survived the 2 h reperfusion period (P less than 0.02 from vehicle). Therefore, the survival rate of the splanchnic artery occlusion shock group of rats receiving SK&F 104353 was improved to 100% compared with 50% survival for the vehicle-treated splanchnic artery occlusion shock group (P less than 0.025). In the splanchnic artery occlusion shock + SK&F 104353 group the increase in the plasma activities of the lysosomal hydrolase, cathepsin D, and the cardiotoxic peptide, myocardial depressant factor, were significantly attenuated in comparison to the splanchnic artery occlusion shock + vehicle group (P less than 0.025). These data indicate that the peptidoleukotriene receptor antagonist, SK&F 104353 is beneficial in splanchnic artery occlusion shock, and furthermore suggests that it may be a therapeutically useful agent in bowel ischemic shock.

Animals↗
PubMed1989

Expression of interleukin 1 beta receptors on blast cells in acute myeloblastic leukemia: comparison with interleukin 1 beta proliferative activity.

We describe here the presence of a single class of interleukin 1 beta (IL-1 beta) receptors on the surface of blast cells freshly obtained from eight acute myeloblastic leukemia patients and one chronic myelocytic leukemia patient in blast crisis. Blast cells possessed a low number of high-affinity receptors (range, less than 10-173 receptors/cell) with a Kd of 1.8-12.8 x 10(-10) M. At the same time, we have investigated the effects of IL-1 on the growth of leukemic blast progenitors, and a significant heterogeneity of responsiveness was observed. IL-1 beta (1 ng/ml) enhanced blast colony formation in six patients. No significant effect was observed by addition of up to 100 ng/ml of IL-1 beta in the remaining three patients. No significant correlation was observed between the receptor number, receptor affinity, and the cellular responsiveness to IL-1; in some acute myeloblastic leukemia cases with apparent IL-1 receptors, no proliferation response to added IL-1 was observed. Our data show that IL-1 alone can enhance blast colony formation and that lack of responsiveness to IL-1 in some acute myeloblastic leukemia patients is not related to the absence of IL-1 receptors on blast cells.

Adult↗
PubMed1989

Restriction fragment length polymorphism caused by a deletion involving Alu sequences within the human alpha 2-plasmin inhibitor gene.

A restriction fragment length polymorphism within the human alpha 2-plasmin inhibitor gene has been detected by Southern blot hybridization using an alpha 2-plasmin inhibitor cDNA probe. This restriction fragment length polymorphism can be attributed to the presence of two alleles, A and B, that are distributed in Hardy-Weinberg equilibrium with frequencies of 73.5% and 2.65%, respectively, in 66 unrelated Caucasian individuals or with frequencies of 51.0% and 49.0%, respectively, in 50 unrelated Japanese individuals. The minor allele, B, is due to a deletion of about 720 base pairs in intron 8 of the alpha 2-plasmin inhibitor gene. Sequence analysis of the deletion junction in allele B and the corresponding regions of allele A demonstrated the presence of oppositely oriented Alu sequences at the 5' and 3' deletion boundaries. These data suggest that this restriction fragment length polymorphism was caused by intrastrand recombination between Alu sequences.

Alleles↗
PubMed1989

[OK 432-induced production of IFN-gamma in peripheral mononuclear cells from healthy subjects and patients with cancer].

OK 432, a well-established immunopotentiator, has been recently noticed as one of biological response modifiers (BRM). IFN-gamma, also called immune interferon, is regarded as an important immunoregulator secreted by T-lymphocytes. In the present study, we measured the in vitro production of IFN-gamma in human peripheral mononuclear cells (PMC) induced by OK 432. PMC were isolated from the peripheral blood with the Ficoll-Conray centrifugation technique. The number of cells for culture was adjusted to 1 x 10(6) cells/ml in RPMI-1640 medium supplemented with 10% fetal calf serum. Incubation was performed over 7 days at 37 degrees C in the presence of OK 432 at 0.17KE/ml in microculture plates. IFN-gamma secreted in the supernatants was measured consecutively during the observation period with radioimmunoassay. IFN-gamma production in PMC from healthy subjects was already detectable at 24 hours of culture and elevated gradually with incubation, reaching as much as 94.3 +/- 44.6 u/ml (mean +/- SD) after 7 days of culture. In contrast, the production of IFN-gamma in patients with cancer was severely suppressed as 21.9 +/- 25.4 u/ml after 7 days of culture (p less than 0.01). Furthermore, both surgical and radiation treatments inhibited the production of IFN-gamma in PMC from patients with cancer.

Biological Products↗
PubMed1989

Autoantibody against platelet glycoprotein IIb/IIIa in a patient with non-Hodgkin's lymphoma.

An autoantibody to platelet glycoprotein (GP) II b/III a was produced in a 38 year-old woman who had a previous history of the malignant lymphoma of the stomach. The aggregations of the patient's platelets showed losses of the primary waves in response to ADP and epinephrine and marked hypoaggregation in response to collagen, while agglutination by ristocetin was normal. Crossed immuno-electrophoresis (CIE) of her platelets solubilized by 1% Triton X-100 revealed an abnormal biphasic precipitate line of GP II b/III a complex. Nine months later, she developed severe thrombocytopenia along with a relapse of the lymphoma in the cervical lymph nodes. The patient's IgG, which was collected during her thrombocytopenic period and purified, inhibited ADP-, epinephrine- and collagen-induced aggregations of normal platelets. In CIE, the 125I-labelled IgG of the patient, inserted into the intermediate gel, was incorporated into the precipitation line of the GP II b/III a complex of normal platelets. Radiation treatment to the cervical lymph nodes dramatically normalized both the function and the count of the patient's platelets. From these findings, it is suggested that an autoantibody to the GP II b and/or III a was produced by the lymphoma cells.

Adult↗
PubMed1989

DNA rearrangement and restriction fragment length polymorphism within the first BCR intron in Philadelphia-positive acute leukemia.

In some patients with Philadelphia (Ph)-chromosome positive acute lymphoblastic leukemias, breakpoints on chromosome 22 are reported to occur within the first BCR intron. To analyze the breakpoints in chromosome 22 of Ph-positive acute leukemia patients without rearrangement of the 5.8 kb bcr, we cloned the 3' part of the first BCR intron using a synthetic DNA probe. During the course of study, we mapped the region of the deletion/insertion of 1 kb that causes a restriction fragment length polymorphism (RFLP) and found a racial difference in the frequencies of the alleles giving rise to this RFLP. Analyses of the patients' samples indicated that breakpoints were located within the 8.5 kb EcoRl fragment of the first BCR intron in two of five Ph-positive acute leukemia patients. The data, together with the previous reports, indicate that breakpoints within this approximately 50 kb intron are widely scattered, in contrast to those confined within the 5.8 kb bcr in chronic myelogenous leukemias.

Acute Disease↗
PubMed1989

Lumboperitoneal shunt for the treatment of postoperative persistent collection of subcutaneous cerebrospinal fluid (pseudomeningocoele).

Ten patients with postoperative collection of subcutaneous cerebrospinal fluid (pseudomeningocoele) refractory to nonsurgical treatment underwent lumboperitoneal (LP) shunt. In all patients rapid resolution of the subcutaneous collection was achieved, and no recurrence was observed during the follow-up period. Complications of the LP shunt included transient sciatica in one patient, and acute subdural haematoma after a mild head trauma in another patient who had had a subdural fluid collection. A LP shunt proved to be a less invasive and reliable method of treatment for this condition when it fails to resolve despite aspiration of cerebrospinal fluid combined with mechanical compression of the wound. However, in cases with subdural fluid collection, early withdrawal of the LP shunt may be recommended.

Adult↗
PubMed1989

Cerebral sinus thrombosis in patients with severe iron deficiency anaemia due to myoma uteri.

Two middle-aged women with haemorrhagic infarction due to thrombosis of the superior sagittal and transverse sinus, respectively, are herein reported. Severe iron deficiency anaemia secondary to myoma uteri seen in these patients was suggested to play a significant role in the development of the sinus thrombosis. In middle-aged women, myoma uteri deserves special attention as a possible aetiological contributor to cerebral sinus thrombosis.

Anemia, Hypochromic↗
PubMed1989

Hemostasis associated with abnormalities of fibrinolysis.

Hemostatic plugs consist of platelet aggregates and fibrin mesh containing blood cells and plasma components. Hemostatic efficiency depends on the rate of formation of hemostatic plugs as well as the structural integrity and stability of the formed hemostatic plugs. Fibrin elements are major constituents contributing to the structural integrity and stability, but they are subject to fibrinolytic activity occurring spontaneously after fibrin formation. Fibrinolysis is usually suppressed by endogenous inhibitors. Increase of a profibrinolytic component or deficiency of an inhibitor would result in an accelerated fibrinolysis, causing a premature lysis of hemostatic plugs before restoration of injured vessels, leading to a hemorrhagic tendency. Such a state can be seen typically in patients with congenital deficiency of alpha 2-plasmin inhibitor or a hereditary increase of plasminogen activator, and it is also seen in acquired situations such as amyloidosis, liver cirrhosis, disseminated intravascular coagulation (particularly in patients with acute promyelocytic leukemia) and thrombolytic therapy. The hemorrhagic tendency can be well controlled by an administration of an antifibrinolytic agent: epsilon-aminocaproic acid or tranexamic acid. In contrast to an accelerated fibrinolysis causing a hemorrhagic tendency, retarded fibrinolysis may predispose an individual to a thrombotic tendency. Retarded fibrinolysis may be due to either an increase in plasminogen activator inhibitors or decrease of plasminogen activators. Quantitative or qualitative deficiency of plasminogen may also lead to a thrombotic tendency.

Antifibrinolytic Agents↗
PubMed1989

Acute effects of unsaturated fatty acids in splanchnic artery occlusion shock.

Diets enriched with omega-3 unsaturated fatty acids are associated with decreased hypercholesterolemia and decreased risk of ischemic and atherosclerotic diseases. We studied the acute intravascular effects of some of these unsaturated fatty acids (i.e., eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) along with omega-6 unsaturated fatty acids, (i.e., linoleic and linolenic acid) in splanchnic artery occlusion (SAO) shock in rats. Anesthetized rats subjected to total occlusion of the celiac and superior mesenteric arteries for 40 minutes followed by reperfusion usually resulted in a fatal outcome 90-120 minutes after releasing the clamps. SAO shock rats treated with the omega-3 unsaturated fatty acid, EPA, exhibited an improved survival time and rate (p less than 0.05 from vehicle) compared to those receiving only vehicle (i.e., 50% ethanol). EPA and DHA treated SAO rats also exhibited lower plasma activities of the lysosomal protease, cathepsin D, free amino-nitrogen compounds, and the cardiotoxic peptide, myocardial depressant factor. These results indicate that omega-3 unsaturated fatty acids, especially EPA, have some acute beneficial effects in SAO shock in rats.

Animals↗
PubMed1989

Monoclonal antibodies to human thrombomodulin whose binding is calcium dependent.

Four monoclonal antibodies to human thrombomodulin were characterized. Binding of two of these antibodies was dependent on the presence of calcium ions, and approximately 5 mM calcium was required for their maximum binding. These two antibodies inhibited the binding of thrombin to thrombomodulin, thereby inhibiting activation of protein C catalyzed by thrombin-thrombomodulin complex. These two antibodies bind to a major active fragment formed by limited proteolytic digestions of thrombomodulin with elastase and trypsin, suggesting that the antibodies bind to the thrombin-binding site (or its vicinity) located in the epidermal growth factor (EGF)-homology domain. One of the other calcium-independent antibodies also inhibited the binding of thrombin and the activation of protein C, but the inhibition was very weak and was observed only when the antibody was present in a molar excess over thrombomodulin. This antibody did not bind to the protease digests of thrombomodulin. Another calcium-independent antibody did not inhibit either thrombin binding or protein C activation, but bound to the active fragment of protease digests, suggesting that the antibody binds to a region other than the thrombin-binding site in the EGF-homology domain. These observations suggest that thrombomodulin undergoes a calcium-dependent conformational change which may occur in proximity to a thrombin-binding site located in the EGF-homology domain.

Antibodies, Monoclonal↗
PubMed1989

Purification of human alpha 2-plasmin inhibitor using monoclonal antibody column chromatography.

alpha 2-Plasmin inhibitor (alpha 2PI) was purified directly from human plasma by using a monoclonal antibody affinity column, which recognizes the reactive site of alpha 2PI. alpha 2PI was eluted from the column under mild conditions with 50% v/v ethyleneglycol containing 0.05% Tween 80 in phosphate-buffered saline, pH 7.4. The yield was around 50% and the specific activity of the purified protein was the same as that of the best product of preparation conventionally purified alpha 2PI.

Antibodies, Monoclonal↗