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Biomedical subjects

M Okuma

Publications and source records attributed to M Okuma.

At least 163 records · Page 9Linked to original sources
PubMed1993

Effect of dobutamine on the arterial ketone body ratio and portal blood flow velocity in cirrhosis.

We studied the relationship between the portal blood flow velocity and the arterial ketone body ratio in patients with chronic liver disease receiving a dobutamine infusion. We used an ultrasonic Doppler duplex system to evaluate the portal blood flow velocity. Dobutamine was given intravenously at 5 micrograms/kg/min for 20 min. Dobutamine infusion induced smaller changes in the portal blood flow velocity and ketone body ratio in liver cirrhosis than in chronic hepatitis. The existence of shunts and the poor increase of the cardiac index in response to dobutamine explained the limited improvement of portal blood flow velocity in cirrhosis patients. The ketone body ratio was improved by dobutamine in cirrhosis patients whose portal blood flow velocity was increased by more than 10%, while this ratio decreased when the increase of it was less than 10%. There was no change in portal oxygen extraction in the cirrhosis group, and portal oxygen uptake only increased when the portal blood flow velocity rose by more than 10%. Dobutamine should only be used to treat liver failure if the portal blood flow velocity is increased by more than 10% or the arterial ketone body ratio is improved by a test infusion.

Blood Flow Velocity↗
PubMed1993

Distribution of mesenteric and splenic blood flow in cirrhosis of the liver as estimated by radionuclide angiography.

We used radionuclide angiography following an injection of 185 MBq Tc-99m tin colloid as a non-invasive method for measuring the mesenteric and portal components of the total hepatic circulation, according to the method of Fleming et al (J Nucl Med 24; 1983). Fifty-seven patients with cirrhosis and 33 controls were examined. The relative mesenteric flow (MF) and the relative portal flow (PF) were 68.6 +/- 8.5% and 78.6 +/- 5.9%, respectively, in the control group. These values were 42.0 +/- 16.4% and 70.9 +/- 8.9%, respectively in the cirrhosis group, and were significantly lower than in the controls. In the cirrhosis group, the reduction in PF was small, while that in MF was large. Consequently, we found that portal blood flow was relatively well maintained in the cirrhosis patients, while the contribution of splanchnic blood flow to the portal flow was relatively reduced.

Adult↗
PubMed1993

Transcatheter hepatic arterial drug infusion therapy for hepatocellular carcinoma. Effect on the arterial ketone body ratio.

The arterial ketone body ratio (acetoacetate to beta-hydroxybutyrate) was measured in 15 patients with chronic liver disease before and after the infusion of anticancer drugs or embolic agents (gelatin sponge or iodized oil) into the hepatic artery. The arterial ketone body ratio decreased after hepatic angiography and decreased further at 15 min after infusion therapy. When the arterial ketone body ratio decreased to 1.0 or less on at least one occasion after infusion therapy, the ratio after hepatic angiography was always 1.35 or less. Such patients developed marked systemic symptoms like fever and severe liver dysfunction. Ascites also developed in three patients in whom the arterial ketone body ratio was reduced to 0.7 or less at 24 h after infusion therapy. The arterial ketone body ratios improved at 3-7 days after infusion therapy. In the seven patients treated with gelatin sponge embolization, the ratio at 3-7 days after therapy was actually higher than that before angiography.

3-Hydroxybutyric Acid↗
PubMed1993

Functional role of the antigen recognized by an antiplatelet antibody specific for a putative collagen receptor in platelet-collagen interaction.

Collagen, a major component of blood vessels, mediates primary hemostasis brought about by platelets. The mechanism underlying platelet-collagen interaction is highly complicated and to date various molecules have been suggested to be platelet collagen receptors. We suggest that a platelet membrane protein with a molecular weight of 62 kDa in the reducing condition (P62) immunoprecipitated by the antibody of a patient with idiopathic thrombocytopenic purpura could be a platelet collagen receptor. The antibody was also primarily immunoreactive with P62 on immunoblotting. The patient's platelets, which were deficient in P62 and totally lacked collagen-induced platelet aggregation, showed normal platelet adhesion to collagen in the presence of Mg2+. However, the Fabs of the antibody, which completely abolished collagen-induced normal platelet aggregation, also had inhibitory effects on normal platelet adhesion to collagen. These results indicate that of the antigens recognized by this antibody, P62 could play an important role in platelet-collagen interaction mediating aggregation, and that multiple membrane molecules, including P62, may participate in platelet adhesion to collagen.

Antibody Specificity↗
PubMed1993

Okadaic acid biologically mimics the role of calcium/phospholipid dependent kinase inhibitors in the process of HL-60 cell differentiation.

Okadaic acid, a newly recognized protein phosphatase inhibitor and a non-TPA type tumor promoter, enhanced 1 alpha 25(OH)2D3(D3)-induced HL-60 cell differentiation into monocyte/macrophage lineage but did not affect dibutyryl cyclic AMP (dbcAMP)-induced differentiation into granulocytic lineage. Okadaic acid alone did not induce any differentiation. The process of D3-induced HL-60 cell differentiation on cultivation in magnesium deficient medium can be divided into two steps namely commitment and phenotypic expression as we have previously reported (J Cell Physiol 1987;131:50; Cell Growth Diff 1991;2:415), and the effect of okadaic acid on each step was studied. The results obtained indicated that okadaic acid inhibited commitment and enhanced phenotypic expression. We have previously shown that PKC has a dual action in the process of differentiation, i.e. as a positive regulatory signal in commitment and as a negative one in phenotypic expression. Thus, although okadaic acid has been reported to enhance the phosphorylation of various proteins that are also phosphorylated by PKC, we found that it mimics the role of PKC inhibitors such as H7 and staurosporine in D3-induced HL-60 cell differentiation.

Calcitriol↗
PubMed1993

[Renal plasmacytoma].

Extramedullary plasmacytoma arising in the kidney is uncommon. So far only 11 cases have been reported. Recently, we noted the 12th case, the third case seen at the Kyoto University Hospital. The literature is reviewed. A 43-year-old man was hospitalized because of paraplegia due to spinal cord compression by the solitary plasmacytoma arising in the cervical spine, producing an IgG-lambda paraprotein. The tumor excision was followed by radiotherapy and standard chemotherapy. Two years later, new lesions on the thoracic spine, the left clavicle, and the occipital bone successively developed with Bence Jones proteinuria (lambda), but without IgG-lambda paraproteinemia. Ga-67 scanning was performed to detect extramedullary tumors. The marked accumulation of the radionuclide revealed intraabdominal tumors. A CT scan of the abdomen revealed a large soft-tissue mass (73 x 50 mm) emanating from the right kidney and several enlarged lymph nodes. Ultrasound of the right kidney revealed a solid mass with hydronephrotic change. RI-renogram showed delayed excretion from the right kidney. Clusters of myeloma cells were repeatedly observed in the urinary sediment. Thus, a diagnosis of plasmacytoma of the kidney was made. Treatment with radiotherapy alone was sufficient.

Adult↗
PubMed1993

Characterization of a novel biphenotypic leukemia cell line, TA-1, with myeloperoxidase and inducible cytoplasmic mu chain: altered rearrangement patterns of antigen receptor genes.

A novel biphenotypic cell line carrying t(9;11)(p22;q23), TA-1, was established from the peripheral blood of a patient with acute undifferentiated leukemia. The TA-1 cells simultaneously expressed lymphoid (CD19, CD20) and myeloid characteristics (CD13, CD33, myeloperoxidase) on the same cells. When the cells were treated with tetraphorbol acetate, cytoplasmic mu chain was induced and the fluorescence intensity of CD13 was increased. These findings suggested that TA-1 cells have a bidirectional maturation capacity, as well as biphenotypic features. Molecular analysis disclosed differences in the rearranged bands, corresponding to one allele of the immunoglobulin heavy chain gene (IgH) and the T cell antigen receptor gamma gene (TCR gamma), between the non-cultured cells and the cell line, while showing identical rearranged patterns of another allele of both these genes and the TCR beta gene. These results suggest that the non-cultured cells and the established cell line have the same clonal origin and that the latter is a clonal descendant of the former.

Acute Disease↗
PubMed1993

[Detection of minimal residual clone after sex-mismatched bone marrow transplantation by fluorescent in situ hybridization].

In our previous paper we reported that fluorescent in situ hybridization (FISH) using DYZ1 and DXZ1 was a highly reproducible technique and cellular chimerism consisting of cells of male and female origins could be detected in the order of 0.1%. In the present study FISH was applied to detect minimal residual clones (MRC) in 10 patients with a variety of leukemias who received sex-mismatched bone marrow transplantation (BMT). In 9 patients who had no signs of recurrence, serial FISHs performed on each patient revealed the presence of 0.1 to 3.2% recipient residual clone. On the other hand, in the remaining one patient 10.6% and 16.9% of MRC were found by FISH performed 6 and 10 months after BMT. Immediately thereafter, this patient was diagnosed as in relapse by bone marrow examination.

Adolescent↗
PubMed1993

[Rapid development of primary amyloidosis after two years' follow-up of monoclonal gammopathy of undetermined significance (MGUS)].

Recently, we have encountered an unusual case of "monoclonal gammopathy of undetermined significance (MGUS)" in which some clinical features indicative of primary and amyloidosis (PA) were observed two years after the diagnosis of MGUS. The patient, born in 1925, was diagnosed of having MGUS (IgG-lambda type M-component level; 1 g/dl) in June 1990. The following clinical features occurred in close succession within five months after a stable course of two years: general malaise, abdominal, distension, pretibial edema and facial puffiness, ecchymoses on the chest wall, and dyspnea on effort. The biopsy specimens from the skin and gastric mucosa revealed amyloid deposition. The M-component levels in the serum and urine as well as the number of bone marrow plasma cells remained unchanged. The various kinds of laboratory examinations indicated that systemic amyloidosis rapidly developed within five months. It seems quite likely that the heart, liver, and spleen may be affected with amyloidosis. It is noteworthy that PA can occur without an increase in the serum M-component level at any time after the diagnosis of MGUS. An early diagnosis of PA as well as multiple myeloma should be kept in mind in the follow-up study of patients with MGUS.

Aged↗
PubMed1993

[Multiple myeloma presenting with amyloid arthropathy].

Amyloid arthropathy rarely occurs in patients with multiple myeloma (MM) or primary amyloidosis (PA). Amyloid infiltration in and about the joints may be so extensive as to simulate the findings of rheumatoid arthritis. Some cases have been reported in which the articular manifestations were present for many months prior to the diagnosis of amyloid arthropathy. The delay of the diagnosis can result in the development of a fatal complication of MM or PA, which is not always unavoidable. We have encountered an unusual case of MM which the articular manifestations were present prior to the diagnosis of MM. A 59-year-old woman had a four-month history of hypesthesia in the median-nerve distribution of both hands and polyarthralgia. Far advanced renal insufficiency was evident, but its etiology was not determined. The patient was maintained on hemodialysis. The shoulders, wrists, hips and finger joints were symmetrically involved with articular swelling. All of these joints showed the avid uptake of Tc-99m (V) DMSA. The serum and urine immunoelectrophoresis demonstrated the presence of IgG-lambda type M-component and lambda type Bence Jones proteins, respectively. The bone marrow findings and bone roentgenograms supported the diagnosis of MM. Biopsy specimens from the synovial membrane revealed amyloid deposition. Her condition was much improved with melphalan and prednisolone.

Amyloidosis↗
PubMed1993

Re-analysis of prognosis in refractory anemia alone, with ring sideroblasts, and with excess of blasts.

Based on 473 primary cases of refractory anemia (RA), RA with ring sideroblasts (RARS), or with an excess of blasts (RAEB), new staging systems for overall survival, leukemic transformation, and nonleukemic death were developed. The reproducibility of these new staging systems, our former staging systems for leukemic transformation and nonleukemic death, and that for overall survival provided by Sanz et al. (Blood 1989;74:395-408), were estimated using a total of 132 patients with RA, RARS, or RAEB (test sample). The correlation of risk ratios of the test sample from our system and that of Sanz et al. was poor (tau = 0.24; Kendall rank correlation). Our risk ratio was a significant (p = 0.0012) continuous covariate of the Cox model life-table analysis in the test sample but that of Sanz et al. was not. The new and previous staging systems for leukemic transformation were highly similar (tau = 0.7) and risk ratios of both systems were significant in the test sample (p = 0.00046 and 0.0017, respectively). Based upon the new system, patients at high risk for leukemic transformation RA or RARS were identified as males, with bone marrow myeloblasts higher than 2.5%, abnormal granules in the granulocytes, and circulating erythroblasts. Their cumulative leukemic transformation rate exceeded 50% within 2 years from presentation. The new and previous systems for nonleukemic death were moderately correlated (tau = 0.47). The risk ratios of both systems were significant in the test sample (p = 0.00012 and 0.000024, respectively) but failed to stratify test sample patients into three distinct risk groups. In conclusion, our new staging systems for overall survival and leukemic transformation were reproducible in RA, RARS, or RAEB patients and will be useful especially in identifying high-risk patients with RA or RARS, who are considered to be at lower risk by the FAB classification.

Adolescent↗
PubMed1992

Down-regulation of interleukin 6 receptors of mouse myelomonocytic leukemic cells by leukemia inhibitory factor.

We examined the effect of leukemia inhibitory factor (LIF) on the expression of interleukin 6 receptors (IL-6R) on mouse myelomonocytic leukemic M1 cells. Binding studies using 125I-labeled human and murine IL-6 revealed that LIF caused a decrease in IL-6 binding to M1 cells. The decrease became evident within 1 h, and the maximum decrease was observed at 3-6 h. Scatchard plot analysis revealed that M1 cells had a single class of high affinity receptors for IL-6 and that LIF-induced decrease in IL-6 binding was due to a decrease in the number of IL-6R on the cell surface and not to changes in their affinity. The affinity of IL-6R on M1 cells to human IL-6 (Kd = 2.25 nM) was about 10-fold lower than that to murine IL-6 (Kd = 200 pM). The amount of IL-6 secreted into culture media by M1 cells that were treated with LIF for up to 12 h was not enough to cause receptor down-regulation. Northern blot analysis demonstrated that IL-6R mRNA was down-regulated by LIF treatment, and similar regulation was also observed when the cells were treated with IL-6. The time course of the IL-6R mRNA level was similar to that of IL-6R expression on the cell surface, suggesting that the main mechanism responsible for the loss of high affinity IL-6R was the regulation of IL-6R mRNA. Although the half-life of IL-6R on the cell surface was about 30 min, the addition of LIF reduced it to 16 min, suggesting the existence of an additional mechanism responsible for the loss of high affinity IL-6R on the cell surface.

Animals↗
PubMed1992

Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that is essential for functional IL-2 binding and signaling.

Functional studies of the interleukin 2 receptor (IL-2R) of two (ED515-D and Kit225) IL-2-dependent and three (ED515-I, 3T3-alpha beta 11, and Hut102) IL-2-independent cell lines were done. All of these cell lines appeared to express high as well as low affinity IL-2R. However, ED515-I and 3T3-alpha beta 11, which expressed the IL-2R beta chain, did not bind IL-2 at all when IL-2 binding to their IL-2R alpha chain was blocked with anti-Tac monoclonal antibody, whereas the intermediate affinity binding in ED515-D, Kit225, and Hut102 cells remained. We tentatively called the high affinity IL-2R of the former cells pseudo-high affinity IL-2R. The dissociation constant of pseudo-high affinity IL-2R was higher than that of ordinary high affinity IL-2R. Internalization of cell-bound 125I-IL-2 into ED515-I and 3T3-alpha beta 11 cells was less efficient than that into ED515-D cells. The addition of IL-2 neither promoted cell growth nor upregulated IL-2R alpha chain expression in ED515-I and 3T3-alpha beta 11 cells. Furthermore, tyrosine phosphorylation of the cellular proteins (p120, p98, p96, p54, and p38) was induced or enhanced in response to the addition of IL-2 in ED515-D and Kit225 cells, but not in the cell lines expressing pseudo-high affinity IL-2R. Finally, 125I-IL-2 crosslinking followed by SDS-PAGE analysis showed an 80-kD band corresponding to p65 + IL-2, in addition to bands corresponding to IL-2R alpha and beta chain + IL-2 in cells bearing ordinary high affinity IL-2R but not in cells with pseudo-high affinity IL-2R. Taken together, we consider that another protein whose molecular mass is approximately 65 kD is functionally important in IL-2 binding and subsequent signal transduction and may be the third component of IL-2R.

3T3 Cells↗
PubMed1992

Interleukin-2 (IL-2) induces erythroid differentiation and tyrosine phosphorylation in ELM-I-1 cells transfected with a human IL-2 receptor beta chain cDNA.

The molecular mechanism of erythroid differentiation has been still ill-defined. In this study, we introduced a human interleukin-2 receptor (IL-2R) beta chain cDNA into ELM-I-1 cells which differentiated into hemoglobin-positive cells in the presence of erythropoietin (Epo), and established the transformant which expressed IL-2R beta chain. In this transformant, we revealed that IL-2 induced erythroid differentiation and the same pattern of tyrosine phosphorylation as Epo. These data suggest that tyrosine phosphorylation is involved in signal transduction pathway of erythroid differentiation. It is also implicated that the Epo and IL-2 receptor system share a common signal transduction pathway.

Animals↗
PubMed1992

Platelet adhesion to collagen-coated wells: analysis of this complex process and a comparison with the adhesion to matrigel-coated wells.

The mechanisms of platelet adhesion to collagen type III-coated wells and Matrigel-coated wells were analyzed. The adhesion of 51Cr-labeled platelets to collagen-coated wells showed a biphasic pattern. The early stage of adhesion was inhibited by antibodies against platelet glycoprotein(GP)s Ia/IIa and VI. The later stage of platelet adhesion was inhibited by an antibody against the GPIIb/IIIa complex and a concomitant release of 14C-labeled serotonin was observed. The percentage of adhered platelets was increased when a higher platelet concentration was added in the reaction medium. These results indicated that the adhesion assay of platelets to collagen-coated wells was composed of two reactions: the first one is the platelet-collagen interaction that depends on GPIa/IIa and GPVI on the platelet surface; and the second reaction is the platelet-platelet interaction, platelet aggregation, which depends on GPIIb/IIIa. The adhesion of platelets to Matrigel-coated wells was indicated to involve platelet-Matrigel interactions that were partly dependent on the laminin in the Matrigel solution.

Antibodies, Monoclonal↗
PubMed1992

Use of proton nuclear magnetic resonance spectroscopy of plasma in screening for malignant disease.

In 1986, narrow plasma proton nuclear magnetic resonance (NMR) methyl and methylene line widths were reported to be associated with malignant disease, but more recent studies have not confirmed this relationship. The authors analyzed 106 plasma samples from healthy control subjects and patients with cirrhosis, hepatocellular carcinoma, metastatic liver tumors, other untreated cancers, and hyperlipidemia. NMR spectroscopy was performed using a proton NMR spectrometer operating at 399.65 MHz. A significant difference was found between the mean line widths of the plasma methyl resonances in control subjects and those in patients with cancer or hyperlipidemia. However, no significant difference was found between the mean plasma methylene line widths in control subjects and patients with cancer. Plasma samples from patients with liver disease or hyperlipidemia showed a characteristic methylene spectral pattern. The methylene pattern could be separated into three types: type A had a small peak on the right shoulder of the main peak; type B was a sharp single peak; and type C was a broad single peak. All control subjects had type A pattern; patients with liver disease had type C pattern; and patients who had hyperlipidemia had type B pattern, and hyperlipidemia may affect methyl and methylene line widths in NMR spectra. Because the methyl and methylene levels and their average line widths correlated inversely with triglyceride levels, considering the spectral patterns that indicate hyperlipidemia should decrease false-positive results and make the methyl line width useful for cancer screening.

Adult↗