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Biomedical subjects

N Oku

Publications and source records attributed to N Oku.

At least 127 records · Page 7Linked to original sources
PubMed1993

Autoimmune thrombocytopenia following peripheral blood stem cell autografting.

A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.5 x 10(9)/l and the platelet count > 50 x 10(9)/l. The platelet count was 145 x 10(9)/l on day 20. Purpura developed on the anterior chest and legs on day 50, at which time the platelet count fell to 17 x 10(9)/l. The BM was hypocellular with an increase in megakaryocytes. Platelet-associated IgG (PAIgG) was 88.1 ng/10(7) platelets (normal range 9-25 ng/10(7)); a diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone administration led to an increase in the platelet count and a decrease in PAIgG. Analysis of lymphocyte subsets revealed an increased number of CD3+ gamma/delta T cells. It is postulated that the thrombocytopenia in this case was due to an autoimmune mechanism such as ITP.

Adult↗
PubMed1993

[Quantitative assessment of cerebral blood flow by 123I-IMP SPECT: venous sampling method with hand warming in the water bath].

In order to establish a noninvasive, quantitative method for measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT, we attempted to employ continuous venous sampling instead of arterial sampling. Forty two patients with cerebrovascular diseases were classified into two groups, with (group II: n = 35) and without (group I: n = 7) hand warming. In group II, either hand was warmed, wrapping in a hot blanket (group IIA) or immersed in a 44 degrees C water bath (group IIB). In each patient, immediately after intravenous bolus injection of 222 MBq IMP, arterial and venous blood samples were collected continuously for 5 min from the radial artery and the cubital vein, respectively. By octanol extraction, IMP was divided into the unmetabolized and metabolized fraction. The ratio of 123I-IMP radioactivity of venous blood compared to arterial blood (pass ratio, referred as %PR) was calculated in three fractions, whole blood, unmetabolized, and metabolized fraction. By using these parameters, we assessed the possibility to estimate the amount of unmetabolized IMP fraction of arterial blood, usually used as an input function, from venous samples. In group I, %PR demonstrated a considerable variation between individuals (whole IMP, 47.5 +/- 24.6% (mean +/- SD): unmetabolized IMP, 46.0 +/- 24.5%: metabolized IMP, 51.8 +/- 27.4%). In group II, especially in group IIB, both increase of %PR value and the decrease in variation (whole, 77.9 +/- 5.6%: unmetabolized, 75.7 +/- 5.7%: metabolized, 86.7 +/- 8.7%) were observed, which permitted the further calculation based on the assumption that %PR value was constant in each IMP fraction (whole blood and unmetabolized fraction).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Chronic myelomonocytic leukemia and esophageal cancer developed in a renal allograft recipient].

A 46-year-old man treated with azathioprine (100-150 mg/day) and prednisolone (10mg/day) for 14 years after allogeneic renal transplantation, was admitted to our hospital in December, 1988 for the evaluation of leukocytosis. His leukocyte count was 32,700/microliters with 38% monocytes and 2% blasts. Chromosomal analysis of the bone marrow revealed 45, XY, -7. He was diagnosed as chronic myelomonocytic leukemia (CMML), and treated with low-dose Ara-C. Two months later, he progressed to overt acute leukemia, and he complained of difficulty in swallowing. Endoscopic examination revealed esophageal cancer. The patient died of respiratory failure on April 18, 1989. This case suggests that immunosuppressive agents might play an important role on the pathogenesis of CMML and esophageal cancer.

Azathioprine↗
PubMed1992

Tumor accumulation of novel RES-avoiding liposomes.

For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA) (Namba, Y., Sakakibara, T., Masada, M., Ito, F. and Oku, N. (1990) Chem. Pharm. Bull. 38, 1663-1666). In this present study, we examined the blood clearance and biodistribution of PGlcUA-liposomes (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 40:40:20 as a molar ratio) in normal and tumor-bearing mice. Liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of PGlcUA was also examined as a control. When [3H]inulin-encapsulated PGlcUA-liposomes and DPPG-liposomes were intravenously injected into normal mice, approx. 50% of the 3H radioactivity was recovered from the liver, the bulk of RES, at 12 h after administration of DPPG-liposomes, while only approx. 20% of it was found there when PGlcUA-liposomes were administered. Radioactivity remaining in the plasma at 12 h after injection was 5-fold higher when PGlcUA-liposomes were injected than when DPPG-liposomes were used. Biodistribution of liposomes in tumor-bearing mice was also examined. Mice were inoculated with 10(7) S180 cells into the hind leg. After 1 week, liposomes were injected. Radioactivity of [3H]inulin originally encapsulated in the PGlcUA-liposomes accumulated in the tumor to an extent 3-4-fold higher than that of the marker in DPPG-liposomes. Liver/tumor ratio of the radioactivity was 12 for DPPG-liposomes and only 2 for PGlcUA-liposomes. This latter value is the lowest of various liposome formulations ever reported.

Animals↗
PubMed1992

Immunophenotype and DNA content of myeloma cells in primary plasma cell leukemia.

To clarify the biological characteristics of the myeloma cells in primary plasma cell leukemia (PCL), we studied the immunological phenotype and DNA content of cells from five patients with primary PCL as compared to those from the patients with typical multiple myeloma (MM). In two of five patients with PCL myeloma cells had B-cell-associated antigens (B1, J5) and surface immunoglobulin in addition to plasma cell associated antigens, suggesting that these cells are immunologically immature as compared to mature plasma cells. Concerning the DNA content of myeloma cells, two of four patients had hypodiploid while two had diploid myeloma cells. In contrast, 24 of the 37 (65%) patients with typical MM had hyperdiploid and 1 had hypodiploid myeloma cells. These observations suggest that the myeloma cells in PCL are immunologically heterogeneous. The increased incidence of hypodiploidy in PCL may explain its relatively poor prognosis as previously shown in those with typical MM and hypodiploid DNA content.

Adult↗
PubMed1992

Liposomal modification with uronate, which endows liposomes with long circulation in vivo, reduces the uptake of liposomes by J774 cells in vitro.

For overcoming rapid removal of liposomes from the bloodstream, we developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In this current study, we examined the in vitro interaction of PGlcUA-liposomes with J774 cells derived from mouse macrophages. Liposomal association with J774 cells at 37 degrees C did not increase compared with the binding at 4 degrees C when liposomes were modified with PGlcUA. RES-avoiding ability was not specifically endowed by glucuronate but by uronates in general, since palmityl-D-galacturonide showed a similar effect on liposomal clearance in vivo and liposomal uptake in vitro. These facts indicate that modification of the liposomal surface with uronic acid derivatives endows liposomes with a long circulation time in the bloodstream by reducing their uptake by macrophages.

Animals↗
PubMed1992

Novel type of clonally involved cytoplasmic immunoglobulin-negative cells in multiple myeloma: flow cytometric study.

In order to identify myeloma cells and their precursor cells, we studied bone marrow samples from 39 patients with multiple myeloma, including 2 with plasma cell leukemia, using dual parameter cytometry of both DNA and cytoplasmic immunoglobulin (Cyt-Ig). Myeloma cells from 25 patients (64.1%) were aneuploid and those from the remaining 14 patients were diploid. In 25 patients with aneuploid myeloma, we found a small component of cells which had aneuploid DNA content without Cyt-Ig in addition to myeloma cells showing aneuploidy with Cyt-Ig. These aneuploid Cyt-Ig-negative cells were considered to be clonally involved because they were aneuploid, and detected predominantly in patients with stage III myeloma. This suggests that these cells may contribute to disease progression. The characteristics of these cells are described and the relationship between these cells and myeloma precursor cells is discussed.

Aneuploidy↗
PubMed1992

Effects of interleukin-3 and interleukin-6 on peripheral blood cells from multiple myeloma patients and their clinical significance.

The effects of interleukin-3 (IL-3) and interleukin-6 (IL-6) on nonadherent mononuclear cells (NMC) from the peripheral blood of 28 patients with multiple myeloma (MM), 3 patients with monoclonal gammopathy of undetermined significance (MGUS), and 3 normal controls were investigated. In 15 of 27 evaluable patients with MM, monoclonal-cytoplasmic-immunoglobulin (cIg)-positive plasma cells appeared from the T-cell-depleted NMC after 10 days of culture in the presence of IL-3 and IL-6. These changes were not observed in the T cell fraction of myeloma blood or in the T-cell-depleted NMC obtained from cases of MGUS or from normal controls. The percentage of cIg-positive plasmacytoid cells after 10 days of culture was significantly higher in the presence of both IL-3 and IL-6 than with each interleukin alone or the control medium. Furthermore, these changes were often observed in untreated patients. These findings suggest that myeloma precursor cells exist in the peripheral blood of MM patients, especially at diagnosis, and differentiate into cIg-positive cells in the presence of IL-3 and IL-6. This assay may be useful in discriminating the early stage of myeloma from MGUS.

Antigens, CD↗
PubMed1992

Silent cerebral infarction as a form of hypertensive target organ damage in the brain.

The incidence, number, size, and location of silent cerebral infarction on 0.1 T magnetic resonance imaging was investigated in 66 hypertensive patients (63 +/- 9 years old; mean +/- SD) and 42 age-matched normotensive subjects (61 +/- 9 years old) to determine the clinical significance of hypertension in silent cerebral infarction. Cerebrovascular risk factors and the severity of hypertensive changes in other major target organs were also investigated. The incidence of silent infarction in hypertensive patients (47%) tended to be higher than that of normotensive subjects (33%) and increased significantly with advancing age. In hypertensive patients, a significantly higher incidence of silent lesions was noted in patients with hypertensive changes in major target organs (72-73% in patients with organ involvement versus 33-39% in those without). The average number of lesions in hypertensive patients was significantly higher than that in normotensive subjects (6.0 versus 2.1), and the lesions in the hypertensive patients were more frequently detected in the brain areas supplied by perforating arteries than those in normotensive subjects (47% versus 24%). These results clearly demonstrate that silent cerebral infarction is frequently seen in older hypertensive patients, especially when moderate hypertensive changes are noted in major target organs, and suggest that hypertensive arterial changes play a crucial role in the occurrence of silent infarction.

Aged↗
PubMed1992

Hepatocyte growth factor and transforming growth factor-beta stimulate both cell growth and migration of human gastric adenocarcinoma cells.

Hepatocyte growth factor (HGF) induced scattering and cell migration of human gastric adenocarcinoma MKN-74. HGF also significantly promoted the growth of MKN-74 cells in a dose-dependent manner, although HGF is reported to be antiproliferative for the growth of tumor cell lines. This result indicates that HGF stimulates cell proliferation of not only normal epithelial cells but also certain carcinoma cells. Furthermore, transforming growth factor-beta (TGF-beta), which is recognized to inhibit the growth of most epithelial cells, additively enhanced both the cell proliferation and migration induced by HGF. These additive effects of HGF and TGF-beta may be responsible for the tumor invasiveness and uncontrolled growth of certain types of carcinoma.

Adenocarcinoma↗
PubMed1992

[Auer rods-positive neutrophils observed at diagnosis increased after remission induction in patient with acute promyelocytic leukemia].

50-year-old male was admitted to our hospital because of gingival bleeding and fever in August 1987. The leukocyte count was 13,300/microliters with 80.5% leukemic promyelocytes and bone marrow was hypercellular with 86.4% leukemic promyelocytes. A small number of mature neutrophils containing Auer rods were seen in bone marrow. On a diagnosis of acute promyelocytic leukemia and treated with induction chemotherapy consisting of behenoyl-arabinofuranosyl cytosine (BHAC), daunorubicin, 6-mercaptopurine (6-MP) and prednisolone (PSL) was reformed. After cytoreduction, leukemic cells reappeared in the peripheral blood, concomitant with mature neutrophils having Auer rods. Vitamin D3 was not effective as a differentiation inducing agent. Complete remission was obtained in November 1987 by the reinduction chemotherapy consisting of BHAC, aclarubicin, 6-MP and PSL. In this case, neutrophils with Auer rods might have been derived from the leukemic clone and differentiation of leukemic promyelocytes by intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Collection of peripheral blood stem cells mobilized by high-dose Ara-C plus VP-16 or aclarubicin followed by recombinant human granulocyte-colony stimulating factor.

We developed an effective method for harvesting large numbers of peripheral blood stem cells (PBSC) for use in autotransplantation. Twenty patients with hematological malignancies were treated with high doses of Ara-C (12 g/m2) and VP-16/aclarubicin followed by administration of rhG-CSF (50 micrograms/m2). The optimal time for starting PBSC collection was determined by monitoring the CD34-positive stem cells in blood using immunomagnetic beads. PBSC were collected with a CS-3000 blood cell separator. A total blood volume between 7000 and 9000 ml was processed in each apheresis. Under these conditions, a total of 64 apheresis procedures was performed in the 20 patients. The mean numbers of mononuclear cells and of CFU-GM harvested per apheresis were 4.1 x 10(8)/kg and 110 x 10(4)/kg, respectively. A number of CFU-GM sufficient for engraftment (> 30 x 10(4)/kg) could be harvested by a single apheresis in 15 of the 20 patients. So far, 11 patients have been transplanted with PBSC and obtained rapid hematopoietic recovery. The median time to recover neutrophils more than 0.5 x 10(9)/l was 10 days, and that for platelets 50 x 10(9)/l was 11 days. This method for harvesting large numbers of PBSC allows safer autotransplantation in patients with chemoradiosensitive tumors, and is applicable to older patients.

Aclarubicin↗
PubMed1992

[Rapid disappearance of M-protein in multiple myeloma complicated by pneumonia during treatment with HLBI].

A 64-year-old female was admitted for treatment of refractory myeloma (IgG-lambda). Because of severe liver cirrhosis, the patient was treated with interferon (IFN) alone (natural IFN 6 x 10(6) IR/day i.m. for 28 days). Pneumonia developed during IFN therapy. The IFN therapy was completed, restoring suppressed IgM and IgA to their normal ranges, while pneumonia was cured by antibiotics. Because the M-component remained, an additional IFN therapy was resumed and M-protein disappeared. As the period within which the M-component disappeared in this case was shorter than that reported previously, we supposed that the pneumonia might have enhance the effects of IFN. To verify this, we administered OK-432 for 4 weeks as a model of immunoactivation by pneumonia between two successive courses of IFN therapy when M-protein reappeared. To monitor the immune state, natural killer (NK) and lymphokine activated killer (LAK) activities were measured: NK activity suppressed by IFN was restored by OK-432 and was suppressed less by subsequent IFN administration. LAK activity was increased by IFN and OK-432. These observations suggested synergic effects of OK-432 on IFN-activated immunity. This case suggests that IFN combined with immunotherapy may be effective in some cases of myeloma.

Drug Administration Schedule↗
PubMed1991

Solubilization of human placental tumor necrosis factor receptors as a complex with a guanine nucleotide-binding protein.

Human placental membranes exhibited high-affinity receptors for tumor necrosis factor (TNF) (Kd = 5.6 x 10(-10) M) with a density of 1.2-1.7 x 10(10) sites/mg protein. The receptors were solubilized from these membranes with 1% Nonidet P-40, and the solubilized receptor was adsorbed to Con A-Sepharose and wheat germ agglutinin agarose columns, indicating that the TNF receptor derived from human placenta contains carbohydrate chains recognized by these lectins. TNF binding activity was eluted from a column of Sephacryl S-300 as a single peak of Mr 300 kDa. The solubilized receptor was further purified by TNF-Sepharose prepared by coupling of TNF to tresyl-activated Sepharose 4B. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the purified sample resolved five major bands of Mr 90, 78, 41, 35, and 11 kDa, suggesting that these polypeptides constitute a multimeric complex with a molecular mass of 300 kDa, as observed in gel filtration study. Furthermore, the TNF-Sepharose-bound fraction demonstrated GTP gamma S binding and GTPase activity. Immunoblot analysis showed that the 41- and 35-kDa polypeptides were recognized by antisera against alpha subunits and beta subunit of GTP-binding proteins, respectively. These results suggest that the native TNF receptor couples to a guanine nucleotide-binding protein to form a large complex structure in human placental membranes.

Binding, Competitive↗
PubMed1991

Prostaglandins antagonize fibroblast proliferation stimulated by tumor necrosis factor.

Tumor necrosis factor (TNF) is known to be a mitogen for human diploid FS-4 fibroblasts. We have shown in an earlier study (Hori et al. (1989) J. Cell. Physiol. 141, 275-280) that indomethacin further enhances the cell proliferation stimulated by TNF. Since indomethacin inhibits the activity of cyclooxygenase, the role of prostaglandins in TNF-stimulated cell growth was examined. Cell growth stimulated by TNF and indomethacin was inhibited by exogenously added prostaglandins (PGE2, PGF2 alpha, and PGD2), among which PGE2 caused the greatest inhibition of cell growth. Treatment of FS-4 cells with 10 ng/ml TNF resulted in the release of prostaglandins (PGE2, 6-keto-PGF1 alpha, PGA2, PGD2, and PGF2 alpha) 2 to 4 fold over that of untreated cells. The amount of all these prostaglandins increased in a time-dependent manner over 6 h after treatment. In both TNF-treated and control cells, PGE2 was released as the predominant prostaglandin. Furthermore, when PGE2 production and DNA synthesis were determined in FS-4 cells treated with increasing doses of indomethacin, these two cellular responses were inversely affected by indomethacin. These data show that prostaglandins induced by TNF antagonize growth stimulatory action of TNF.

Arachidonic Acids↗