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Biomedical subjects

T Koike

Publications and source records attributed to T Koike.

At least 433 records · Page 24Linked to original sources
PubMed1995

Antiphospholipid syndrome and the idiotypic network.

To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS), have similar pathogenic potential, we have employed an experimental model of antiphospholipid syndrome. Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, derived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and clinical manifestations of APS. The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphatidyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM1B9, although derived from a patient with SLE and with secondary APS, did not react with phospholipids. Immunization of naive BALB/c mice with EY2C9 was followed by production of sustained high titers of antiphospholipid antibodies associated with prolonged activated partial thromboplastin time (APTT) (46.8 +/- 5.0 s vs. 22.4 +/- 1.7 s, in the non-immunized mice). Mice immunized with TM1B9 had a more moderate titer of antiphospholipid antibodies and did not show prolonged APTT. The pregnant mice, that were immunized with EY2C9, had increased fetal resorption rate (the equivalent of fetal loss in the human) of 36.8 +/- 10% (vs. 2 +/- 4% in mice immunized with TM1B9). Our results confirm that monoclonal aCL, derived from a patient with APS, can have a pathogenic potential, dysregulating the idiotypic network and leading to the development of characteristic signs of APS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Severe hepatic involvement without inflammatory changes in systemic lupus erythematosus: report of two cases and review of the literature.

Hepatic diseases in systemic lupus erythematosus (SLE) are not rare, but liver biopsies of those cases are usually reported as chronic hepatitis or steroid-induced steatosis. We describe two unusual patients with active SLE who displayed liver dysfunction without inflammatory changes or associated with drug administration. A liver biopsy in case 1 showed massive hepatic cell damage resulting in acute hepatic failure. In case 2, the liver specimen revealed diffuse fatty degeneration without symptoms specific to liver dysfunction. No inflammatory cell infiltrate was observed in the liver tissue of either patient. After steroid pulse therapy (case 1) and the administration of 60 mg/day of prednisolone (case 2), liver function improved in parallel with the stabilization of the other manifestations of SLE. No other causes for liver damage except for SLE were observed in either case. Therefore it is supposed that the liver impairments in these cases were one manifestation of SLE.

Adult↗
PubMed1995

Fibrinolytic therapy for acute embolic stroke: intravenous, intracarotid, and intra-arterial local approaches.

To clarify the efficacy and limitations of the intra-arterial local infusion of a high-dose fibrinolytic agent for acute embolic stroke, we analyzed the results of 44 patients and compared them with those of 51 patients treated with intracarotid (18 patients) or intravenous (33 patients) infusion therapy. Ten megaunits of recombinant tissue plasminogen activator or 24 x 10(4) IU of urokinase were administered through a microcatheter placed into or proximal to an embolus for 20 minutes. When arterial recanalization was not achieved, a second or third infusion was performed. The rates of complete and partial recanalization just after the local infusion were 52 and 32%, respectively. They were high in middle cerebral and basilar artery occlusion and low in internal carotid artery occlusion (69, 78, and 20%, respectively). In our use, there was no difference between tissue plasminogen activator and urokinase in restoring blood flow. The mean time interval from onset to recanalization in patients with middle cerebral artery occlusion showing marked improvement was 4.8 hours, and it was 5.8 hours with basilar artery occlusion. The size of infarction was reduced, and the outcome was good in patients with complete recanalization achieved. The incidence of hemorrhagic infarction within 24 hours was 22%, and only one patient clinically deteriorated. In the intracarotid infusion group (20 x 10(4) IU of urokinase for 30 min), only two patients showed partial recanalization without clinical improvement. The incidence of hemorrhagic infarction was 28%. The outcome in this group and the intravenous infusion group (18 x 10(4) IU of urokinase a day for 1 wk) was poor compared with that in the local infusion group showing complete recanalization. This preliminary study appears to suggest that intra-arterial local fibrinolytic therapy could be a new strategy for acute embolic stroke.

Acute Disease↗
PubMed1995

Hemostasis in spontaneous subarachnoid hemorrhage.

To comprehensively examine changes in the hemostatic systems early after spontaneous subarachnoid hemorrhage (SAH) and to assess the relationships between those changes and neurological findings, computed tomographic findings, and clinical outcomes, we reviewed 167 patients who were admitted within 24 hours of the onset of SAH. Blood was taken from all of the patients at admission for detailed examinations of the hemostatic systems. The following results were obtained: 1) the levels of the thrombin-antithrombin complex (elevation indicating the activation fo the blood coagulation system), plasmin-antiplasmin complex, and D-dimer (elevation indicating the activation of the fibrinolytic system) significantly increased with the neurological severity, amount of subarachnoid clot, and severity of clinical outcome; 2) the levels of the thrombin-antithrombin complexes and plasmin-antiplasmin complexes were significantly higher in patients with intracerebral or intraventricular hematomas than in patients without those hematomas; 3) in each of almost all the neurological and computed tomographic grades, the levels of the thrombin-antithrombin complexes were significantly higher in the patients with poor outcomes than in those with good outcomes; 4) the poor outcome rate significantly increased with neurological severity and the amount of subarachnoid clot. These data suggest that the activation of the blood coagulation system as well as of the fibrinolytic system occurred early in the course of SAH and that these systems were activated to a greater extent with the severity of neurological grades, computed tomographic findings, and clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm, Ruptured↗
PubMed1995

Blood pressure monitoring in feeding arteries of cerebral arteriovenous malformations during embolization: a preventive role in hemodynamic complications.

To study the hemodynamics of arteriovenous malformations and to avoid hemodynamic complications during and after artificial embolization, we measured arterial blood pressures in 21 feeders in 14 patients through a microcatheter system. Before embolization, the pressures were significantly low in feeders with branches terminating in the malformation (terminal divided branches) and comparatively low in arteriovenous malformations with rapid blood flow through the malformation. The pressures in feeders with brain-nutrifying branches distal to the nidus (transient branches) were significantly high. Therefore, transient branches might be distinguishable from terminal divided branches with the use of feeder pressure monitoring. A hemorrhagic complication occurred in one patient. The feeder pressure in this patient was low before embolization and showed the maximum change among the patients after embolization. It seems that the lower the feeder pressure, the more likely complications are to occur, owing to remarkable hemodynamic alterations. Feeder pressure monitoring may be useful for preventing hemodynamic complications, especially when angiographic findings show feeding arteries giving off terminal divided or transient branches or rapid blood flow through the malformation.

Adolescent↗
PubMed1995

A case of deoxycorticosterone-producing adrenal adenoma.

A 29-year-old woman with deoxycorticosterone (DOC)-producing adrenocortical adenoma had hypertension and hypokalemia but without Cushingoid features. Plasma renin activity and the aldosterone concentration were low, while the DOC concentration was high (6.10-10.3 ng/ml; normal range 0.03-0.33). Plasma cortisol, androgens, and estrogens as well as urinary 17-OHCS and 17-KS were within normal limits. Furosemide administration and two hours upright posture resulted in a 3-fold increase in plasma DOC, but the administration of ACTH, dexamethasone, or angiotensin III had no effect on plasma DOC. Following resection of a right adrenal tumor weighing 70 g, the hypertension and hypokalemia disappeared. DOC content in the tumor was high. On light microscopic examination, the tumor was encapsulated, composed of cells with clear cytoplasm and large nuclei and there were extensive areas of fibrosis and infiltration of lymphocytes. According to Weiss's criteria, the tumor was considered to be an adrenocortical adenoma. Immunohistochemically, P450scc, 3 beta HSD, P450C21 and P45011 beta were positive with heterogeneity of intra-tumoral expression. No immunoreactivity for P45017 alpha in this adenoma was detected. This is different from a previous report in which a relatively small number of cells in DOC-secreting adrenocortical carcinoma were positive for P45017 alpha.

Adrenal Cortex Neoplasms↗
PubMed1995

[A case of mixed connective tissue disease with acute interstitial pneumonitis].

A 43-years-old woman was admitted to the Hokkaido University Hospital because of high fever, muscle weakness and dyspnea in May 1993. She had has muscle weakness of upper extremities since December 1992. She had developed swollen hand, polyarthralgia and Raynaud's phenomenon. High fever and severe dyspnea developed in May 1993. Chest roentogenogram was normal in April 1993. Physical examination showed Velcro rales in both lower lung fields. Her laboratory data showed increased muscle enzymes, high titers of anti-nuclear-antibody (1: 1280) and anti-RNP-antibody (index 199.4 (normal < 7)). Anti-DNA, anti-Sm and anti-Jo-1-antibodies were all negative. Blood gas analysis showed severe hypoxemia. Chest roentogenogram revealed diffuse bilateral interstitial infiltrates prominent in the bases. Diagnosis of mixed connective tissue disease with acute interstitial pneumonitis was made. She was treated with steroid pulse therapy (methylprednisolone 1 g x 3 days) followed by high dose oral prednisolone (60 mg/day), and diffuse interstitial infiltrates disappeared within one week. Prednisolone could be tapered to 17.5 mg/day without relapse. Acute interstitial pneumonitis is a rare complication of mixed connective tissue disease, but may be life threatening. In such cases, high dose steroid therapy should be started without delay.

Acute Disease↗
PubMed1995

Efficacy of delayed granulocyte colony-stimulating factor after full dose CHOP therapy in non-Hodgkin's lymphoma: a pilot study for a leukocyte count oriented regimen.

Bone marrow toxicity is a great challenge for physicians treating patients with non-Hodgkin's lymphoma (NHL) and prescribed chemotherapy. Granulocyte colony-stimulating factor (G-CSF) prevents myelotoxicity, but the optimal timing and scheduling of G-CSF administration has not been ascertained. We investigated leukocyte count oriented G-CSF administration schedules, as related to full dose administration of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy, with shortened intervals. Thirty-eight Japanese patients with NHL were included in this study. The standard CHOP combination was administered in six cycles. Patients were given G-CSF in a dose of 2 micrograms/kg/day, subcutaneously starting the day when total leukocytes were < 3,000/microliters. When leukocyte count remained at > 3,000/microliters, G-CSF was started 10 days following CHOP. Treatment with G-CSF was discontinued after the leucocyte count reached > 10,000/microliters, and CHOP was started the next day (CHOP-G treatment; CHOP-G). Doses were not modified in any patient. Patients over 70 years of age received 2/3 of the standard dosage. In the first cycle of CHOP, the day of initiation of G-CSF was 9.6 days following CHOP in the first cycle and 7.7 to 8.5 days during 2 to 6 cycles. The mean duration of G-CSF injection was 7.4 days with a range from 6.8 to 8.0 days, in each CHOP cycle. The mean intervals of CHOP-G was 14.7 days during six consecutive courses, and there was no prolongation of the intervals, even in later cycles. In 23 patients who received all six cycles of CHOP-G, the overall response rate was 91.3% (73.9% complete remission; CR and 17.4% partial remission; PR). In 32 patients with intermediate grade NHL, the overall response rate was 84.4% (65.5% CR and 18.8% PR). Thus, the full dose CHOP with G-CSF, based on the leukocyte count oriented schedule, can be achieved with shortened intervals, an approach which will increase the quality of life (QOL) for the patients by reducing the days of treatment as well as the cost of G-CSF.

Adolescent↗
PubMed1995

Inhibition of GM-CSF production by recombinant human interleukin-4: negative regulator of hematopoiesis.

Interleukin-4 (IL-4), also known as B-cell stimulatory factor-1 (BSF-1), was initially identified as a T-cell product that mediates anti-IgM-induced DNA synthesis in B-lymphocytes. Various aspects of this highly pleiotropic cytokine have been described, including those on hematopoietic progenitor cells. However, the role of IL-4 in the hematopoietic system has been given different interpretations. Normal human hematopoietic progenitor cells do not proliferate under control of the autocrine system and cytokines are needed for proliferation and differentiation. However, IL-4 in itself does not support proliferation of these cells and if this is the case, the effects of IL-4 on hematopoietic progenitor cells still need to be investigated from the point of view of synergism with other cytokines as well as the control of accessory cells in the production of cytokines. We describe here some properties of IL-4 in association with cytokine production, with special emphasis on granulocyte-macrophage colony-stimulating factor (GM-CSF) production.

Animals↗
PubMed1995

Natural history of intracranial cavernous malformations.

The authors have reviewed the clinical records of 110 patients with intracranial cavernous malformations diagnosed by histological examination and/or magnetic resonance imaging over a mean follow-up period of 4.71 years. These cases were divided, based on their presentation, into a hemorrhage group, a seizure group, and an incidentally diagnosed group. The rate of subsequent symptomatic bleeding was investigated in relation to age at onset, sex, and location of the initial lesion. A high rate of subsequent symptomatic bleeding episodes was found in the hemorrhage group, especially among younger females. The nonhemorrhagic-onset cases had a very low incidence of bleeding. The outcome was generally good, except in patients with lesions in the basal ganglia and brainstem. These findings will be helpful in planning a rational therapeutic strategy for intracranial cavernous malformations.

Adolescent↗
PubMed1995

Concurrent use of granulocyte colony-stimulating factor with low-dose cytosine arabinoside and aclarubicin for previously treated acute myelogenous leukemia: a pilot study.

We used a new chemotherapy regimen for the treatment of 18 consecutive patients with relapsed AML (median age 44 years, range 18-74). The regimen consisted of low-dose cytosine arabinoside (10 mg/m2/12 h, usually day 1 to 14), low-dose aclarubicin (10-14 mg/m2/day, day 1 to 4), and concurrent use of G-CSF (200 micrograms/m2/day) (CAG regimen). Overall, 15/18 patients (83%) achieved complete remission (CR) after one or two courses, including eight out of ten refractory patients with early relapse, second or subsequent relapses, and/or resistant relapse. Two of three patients who relapsed, achieved CR again after reinduction with a modified CAG regimen. Fourteen of the 15 complete remitters received consolidation therapy with the CAG regimen modified, followed by oral busulfan in eight cases, and by allogeneic bone marrow transplantation in two cases. At a median follow-up of 12 months, median CR duration and survival were 6 months and 17 months, respectively. Myelosuppression in the first course of induction therapy was moderate to severe. However, severe non-hematologic toxicity (WHO grade > or = 3) was characteristically rare. Although this is a preliminary study, the CAG combination seems promising for the treatment of relapsed AML, with its low toxicity contributing to a higher quality of life for the patient.

Aclarubicin↗
PubMed1995

[Complete remission achieved by low-dose Ara-C, aclarubicin and rhG-CSF (CAG) therapy in acute non-lymphocytic leukemia with monosomy 7 occurring after severe aplastic anemia].

We report a case of acute myelogenous leukemia (AML), which developed from severe aplastic anemia (SAA) and was successfully treated by low-dose Ara-C and aclarubicin with concomitant use of G-CSF (CAG therapy). A 37-year-old male was admitted for scrutiny of pancytopenia and diagnosed as SAA because of hypocellular bone marrow without abnormal or dysplastic cells. Although hematopoiesis recovered with steroid pulse therapy followed by administration of anabolic steroids, 29 months after initial onset of SAA, he presented as AML (FAB-M6), as his bone marrow Contained 21.6% leukemic myeloblasts and 56% of erythroblasts. Chromosome study revealed 45, XY, -7 in 14 of 20 cells analyzed. Complete remission was achieved by administration of low-dose Ara-C (20 mg/m2 for 7 days) and aclarubicin (14 mg/m2 for 4 days) along with G-CSF (200 micrograms/m2 for 7 days), without any severe complications. In the previous reports in Japan since 1982, 7 out of 8 cases with AML developing from SAA died within a year. Our results indicate that CAG therapy is useful for treatment for this subset of AML with poor prognosis.

Aclarubicin↗
PubMed1995

[Comparison of low-dose cytosine arabinoside and aclarubicin in combination with granulocyte colony-stimulating factor to intermediate-dose cytosine arabinoside and mitoxantrone with or without etoposide in the treatment of relapsed acute myeloid leukemia].

We used a new chemotherapy regimen for the treatment of 18 consecutive patients with relapsed AML. The regimen consisted of low-dose cytosine arabinoside (Ara-C), low-dose aclarubicin and concurrent use of G-CSF (CAG regimen). Fifteen out of 18 patients (83%) achieved complete remission (CR). Median CR duration and median survival were 6 months and 15 months, respectively. These results were similar to those of previously reported salvage therapies for relapsed AML including intensive chemotherapy consisting of intermediate-dose Ara-C and sequential mitoxantrone with or without etoposide (MC/MEC), which we previously adopted. Myelosuppression and non-hematological toxicities were apparently lower and less frequent compared to MC/MEC. The CAG regimen seems promising for the treatment of relapsed AML with its low toxicity contributing to a high quality of life for the patient.

Aclarubicin↗
PubMed1995

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↗
PubMed1995

Establishment and characterization of a novel human immature megakaryoblastic leukemia cell line, M-MOK, dependent on fibroblasts for its viability.

A novel fibroblast-dependent human immature megakaryoblastic leukemia cell line (M-MOK) was established from the bone marrow of a girl with acute megakaryoblastic leukemia, and its growth was determined to be completely dependent on the presence of human embryonic lung-derived fibroblasts, HEL-O. Adhesive interaction between M-MOK and HEL-O was crucial for viability; once HEL-O was removed from the culture, mortality was total within a few days. On HEL-O cells, M-MOK could be passaged for more than 2 years. With regard to surface marker profile, the established cells were positive for CD11a, CD13, CD18, CD33, CD34, CD41b, CD42b, CD54, and c-kit antigens, but negative for HLA class II antigen and glycophorin. Histochemically, the cells were negative for myeloperoxidase, nonspecific esterase, and naphthol ASD chloroacetate esterase staining. Electron-microscope examination revealed the cells to be negative for platelet peroxidase (PPO). After induction of differentiation by a phorbol ester, however, the cells were demonstrated to be positive for PPO with a morphological change to megakaryocytes. From these results, M-MOK was considered to represent an immature cell line of megakaryocyte lineage. Studies of the mechanisms sustaining the HEL-O-dependent continuous in vitro growth of M-MOK cells revealed the following results: (1) M-MOK could grow even when separated from HEL-O by a nucleopore membrane; (2) conditioned medium (CM) from HEL-O supported the growth of M-MOK for more than 1 month without feeder cells; (3) the growth of M-MOK on HEL-O or CM supplement was nearly entirely inhibited by anti-GM-CSF (1 microgram/mL); (4) GM-CSF mRNA was detected in HEL-O cells; and (5) HEL-O was found to secrete GM-CSF into the culture medium. Taken together, the growth of M-MOK might therefore be driven by a soluble factor, that is, GM-CSF secreted from HEL-O cells. The presence of HEL-O, however, inhibited anti-GM-CSF-induced M-MOK death. Co-culture of M-MOK and HEL-O cells thus offers a useful experimental model for analysis of interactions between hematopoietic stem cells and stromal cells.

Base Sequence↗