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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 181 records · Page 10Linked to original sources
PubMed1997

Monophosphoryl lipid A enhances both humoral and cell-mediated immune responses to DNA vaccination against human immunodeficiency virus type 1.

To enhance immunity induced by DNA vaccination against human immunodeficiency virus type 1 (HIV-1), we evaluated the efficacy of monophosphoryl lipid A (MPL), an adjuvant of bacterial origin. BALB/c mice were intramuscularly injected with immunogenic DNA, encoding the env and rev genes of the HIV-1(IIIB) strain, formulated with MPL dissolved in different vehicles (MPL in stable emulsion and MPL in aqueous formulation). The sera from mice immunized with the two preparations of MPL revealed 2(6) to 2(9) times higher HIV-1-specific immunoglobulin G (IgG) titers than the sera from mice immunized without MPL. In virus neutralization tests for HIV-1(IIIB), by p24 assay and antifusion assay of infected MOLT-4 cells, MPL tends to elicit antibody more protective than antibody elicited without adjuvant. MPL also elicited stronger delayed-type hypersensitivity and cytotoxic-T-lymphocyte activity against HIV-1(IIIB) compared to DNA alone. HIV-1-specific IgG subclass analysis showed that MPL tends to facilitate IgG2a production, suggesting enhancement of a predominant T-helper-type-1 response, and this enhancement may help to facilitate protective-antibody induction. Furthermore, a chloramphenicol acetyltransferase (CAT) assay was employed to determine whether MPL affected the gene expression process. Interestingly, both MPL preparations reduced CAT activity in the muscle injected with CAT expression vector but increased anti-CAT antibody production. These results indicate that MPL acts as an effective adjuvant for immunogenic DNA injection despite reduced expression of encoding protein in muscle. We conclude that MPL has a strong adjuvant effect on DNA vaccination against HIV-1.

AIDS Vaccines↗
PubMed1997

Effects of fenoterol on ventilatory response to hypercapnia and hypoxia in patients with chronic obstructive pulmonary disease.

BACKGROUND: It has previously been shown that fenoterol, a beta 2 adrenergic agonist, increases the ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) in normal subjects. The effects of beta 2 adrenergic agonists on chemoreceptors in patients with chronic obstructive pulmonary disease (COPD) remain controversial. This study was designed to examine whether fenoterol increases the HVR and HCVR in patients with COPD. METHODS: The HCVR was tested in 20 patients using a rebreathing method and the HVR was examined using a progressive isocapnic hypoxic method. The HCVR and HVR were assessed by calculating the slopes of plots of occlusion pressure (P0.1) and ventilation (VE) against end tidal carbon dioxide pressure (PETCO2) and arterial oxygen saturation (SaO2), respectively. Spirometric values, lung volumes, and respiratory muscle strength were also measured. The HCVR and HVR were examined after the oral administration of fenoterol (15 mg/day) or placebo for seven days. RESULTS: Fenoterol treatment increased the forced expiratory volume in one second (FEV1) and inspiratory muscle strength. In the HCVR the slope of P0.1 versus PETCO2 was increased by fenoterol from 0.35 (0.23) to 0.43 (0.24) (p < 0.01). Moreover, the P0.1 at PETCO2 of 8 kPa was higher on fenoterol than on placebo (p < 0.05) and the VE was also greater (p < 0.01). In the HVR fenoterol treatment increased the P0.1 at 80% SaO2 from 0.90 (0.72) to 0.97 (0.55) kPa (p < 0.05) while the slopes of the response of P0.1 and VE were not changed. CONCLUSIONS: Fenoterol increases the ventilatory response to hypercapnia in patients with COPD, presumably by stimulation of the central chemoreceptor. The hypoxic ventilatory response is only slightly affected by fenoterol.

Adrenergic beta-Agonists↗
PubMed1997

Relationship between Asbestos Exposures and 8-Hydroxydeoxyguanosine Levels in Leukocytic DNA of Workers at a Chinese Asbestos-material Plant.

The objective of the study was to evaluate the level of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of peripheral-blood leukocytes as a biological marker of asbestos exposure and/or its fibrotic effects in an occupational population exposed to asbestos. The setting was a large-scale asbestos plant in China producing brake linings, asbestos rubber, and textile using chrysotile. From a base population of active and retired workers with various levels of cumulative exposure to asbestos and grades of asbestosis, 39 study subjects were randomly selected to reflect incremental grades of asbestosis based on Chinese diagnostic standards. They consisted of 19 "normal" (control) and ten "suspected" and ten "definite" asbestosis-grade subjects, group-matched for age and sex. Leukocytic DNA was extracted from 5-mL samples of peripheral blood and 8-OHdG level measured by high-pressure liquid chromatography. A cumulative asbestos exposure index (CEI) was calculated for each subject as the summed product of duration and level of asbestos exposure per job, incorporating a job-exposure matrix. Geometric mean 8-OHdG levels showed a positive gradient in relation to increasing grades of asbestosis (control: 1.78, suspected: 2.21, definite: 2.58), with a significant difference between the control and definite-asbestosis subgroups (p < 0.05). The 8-OHdG level of the two subgroups combined as one "asbestosis" group was significantly higher than that of the control group (control: 1.78, asbestosis: 2.39, p = 0.01). Further, 8-OHdG levels were moderately correlated with CEIs for all subjects (r = 0.35, p < 0.05) and with grades of asbestosis for all (r = 0.47, p < 0.01) and for male subjects (r = 0.43, p < 0.05). In multiple regression analyses, grade of asbestosis explained 27% of the total variation in 8-OHdG and was a better predictor than CEI or duration of exposure. Thus, the 8-OHdG level in leukocytic DNA is related to grade of asbestosis and to individual cumulative exposure and may serve as a biologic marker reflecting the status of oxidative DNA damage by asbestos.

Journal Article↗
PubMed1997

Patterns of inspiratory muscle shortening during hypoxia and hypercapnia in dogs.

The shortening of parasternal intercostal muscles (Para) and crural (Cru) and costal diaphragms (Cos) are not precisely understood. We therefore examined shortening patterns of these inspiratory muscles by using chronically implanted sonomicrometers in dogs. To avoid acute effects of surgery, measurements were performed 3 weeks after implanting the sonomicrometers. Patterns of length changes of Para, Cru, and Cos were measured during hypoxia and hypercapnia under two levels of anaesthesia. Respiratory length change (delta L) was assessed as a percentage change relative to the resting length at functional residual capacity (LFRC). Peak tidal shortening was defined as the maximal change from LFRC (delta L/LFRC). Under light anesthesia, the delta L/LFRC was the same among the three muscle groups at all tidal volumes (VT). Under deep anaesthesia, the delta L/LFRC both of Cru and Cos exceeded that of Para. Under light anaesthesia, the maximal shortening velocity ((delta L/LFRC)/delta t) of Cru was greater than that of Para. Under deep anaesthesia, the (delta L/LFRC)/delta t of Para was exceeded by that both of Cru and Cos. Furthermore, the (delta L/LFRC)/delta t of each inspiratory muscle was greater during hypoxia than during hypercapnia at equal volume. We conclude that: 1) the contribution of the diaphragm to ventilation increases during deep anaesthesia; 2) the muscle shortening velocity during hypoxia or hypercapnia is lower in parasternal intercostal muscles than in the diaphragm; and 3) there is no difference in the shortening pattern between crural and costal diaphragms.

Anesthesia↗
PubMed1997

Effects of cardiac sympathetic nerve stimulation on the left ventricular end-systolic pressure-volume relationship and plasma norepinephrine dynamics in dogs.

The effects of cardiac sympathetic nerve (CSN) stimulation on the left ventricular end-systolic pressure-volume relationship (ESPVR) and plasma norepinephrine (NE) concentration in arterial blood were studied in dogs. In 12 anesthetized and open-chest dogs, left ventricular pressure and volume were measured simultaneously with a microtip catheter and a conductance catheter, respectively. The ESPVR values were constructed from pressure-volume loops during a brief occlusion of the inferior vena cava before and after a 40-sec train of electrical CSN stimulation. The slope (Emax) of the ESPVR line was significantly greater after CSN stimulation than before CSN stimulation (p < 0.05) for both right and left CSN stimulation. The increased Emax values after right and left CSN stimulation were not significantly different from each other. In 5 dogs, time courses of Emax, left ventricular systolic pressure, heart rate, and plasma NE concentration after CSN stimulation were studied. Left ventricular systolic pressure and heart rate returned to the baseline more rapidly than Emax and arterial plasma NE concentration. There was a positive, linear correlation between Emax (y) and arterial plasma NE concentration (x), shown as y = 3.3 x 10(-3)x + 3.1 (n = 30, r = 0.86, p < 0.05). These results imply that cardiac contractile enhancement is reflected in arterial plasma NE concentration in conditions in which CSN is activated.

Animals↗
PubMed1997

Torsades de pointes complicating pentamidine therapy of Pneumocystis carinii pneumonia in acute myelogenous leukemia.

Pentamidine isethionate induced torsades de pointes in a 33-year-old woman with acute myelogenous leukemia. This is the first report of Pentamidine-induced torsades de pointes in Japan for over ten years. On the 4th day of intravenous pentamidine for Pneumocystis carinii pneumonia, asymptomatic sinus bradycardia was noted with QT interval prolongation, and torsades de pointes were revealed on the 8th day. Although torsades de pointes was dissolved with discontinuation of the intravenous pentamidine and administration of magnesium sulfate, sinus bradycardia and prolonged QT interval persisted. Ventricular pacing resulted in no arrhythmia and normalization of the QT interval on the 10th day after discontinuation of pentamidine. Careful monitoring of the electrocardiogram should be carried out during intravenous pentamidine therapy.

Adult↗
PubMed1997

[Minimally differentiated hypoplastic leukemia in two elderly patients].

Patient 1; A 78-year-old woman was admitted to our hospital because of general malaise. Her peripheral blood count showed bicytopenia of 900/microliter with 2% blasts, 7.0 g/dl hemoglobin, and 199,000/microliter platelets. Examination of bone marrow revealed hypocellular marrow with peroxidase-negative blasts (89%). Surface marker analysis of blast cells revealed CD13 agents. Electron-microscopically, myeloperoxidase staining was positive. The diagnosis was hypoplastic leukemia in which blasts had a feature of minimally differentiated acute myeloid leukemia (AML-MO). Patient 2; A 78-year-old man was admitted to our emergency unit because of dizziness and dyspnea on exertion. Examination of peripheral blood showed pancytopenia but no blast cells. Examination of bone marrow showed a markedly hypocellular marrow with 38% blast cells. These blast cells were negative for myeloperoxidase and they had CD13 antigen on their surfaces. The diagnosis was minimally differentiated hypoplastic leukemia. At the time of this writing these two patients had been receiving only red cell transfusions for about six months, and the disease had not progressed.

Aged↗
PubMed1997

[Complete remission achieved by L-asparaginase, vincristine and prednisolone (LVP) therapy in secondary leukemia (M5a type) with an MLL gene rearrangement].

A 16-year-old boy was operated upon for synovial sarcoma of the right thigh and underwent chemotherapy consisted of adriamycin (320 mg), cisplatin (780 mg), etoposide (4,200 mg) and ifosfamide (30,000 mg). He developed secondary leukemia 18 months after the chemotherapy. Acute lymphoblastic leukemia (L3) was initially diagnosed because of poor staining of alpha-naphtyl butylate esterase and induction chemotherapy with the LVP regimen (L-asparaginase 5,000 U/m2 day 8-21, vincristine 1.5 mg/ m2 day 1, 6, 11, 16, 21, 26, prednisolone 40 mg/m2 day 1-28) was performed. After the therapy was initiated, the leukemia was finally diagnosed as acute momocytic leukemia (M5a) because of the following data; blasts were positive for CD33 and HLA-DR and negative for CD10, CD19 and CD20; serum lysozyme was 104.0 micrograms/ml; re-evaluation revealed that blasts were strongly positive for alpha naphtyl butyrate esterase in a small part of the slides; 95% of the bone marrow cells showed t (9; 11) chromosomal aberration; gene rearrangement was positive for MLL and negative for JH, JK and TCR C beta 1. Nevertheless, complete remission was obtained after 1 course of LVP therapy. He received bone marrow transplantation from an unrelated volunteer donor after 3 courses of consolidation therapy. He has remained in complete remission for 16 months.

Adult↗
PubMed1997

Autoantibody selectively inhibits binding of von Willebrand factor to glycoprotein ib. Recognition site is located in the A1 loop of von Willebrand factor.

A 20-year-old man with severe von Willebrand disease recently presented a progressive bleeding tendency, characterized recurrent subcutaneous hemorrhages and cerebral hemorrhage. Mixing and infusion studies suggested the presence of an inhibitor directed against vWF:RCo activity of von Willebrand factor (vWF) without significant inhibition of the FVIII:C. The inhibitor was identified as an antibody of IgG class. The inhibitor inhibited the interaction of vWF in the presence of ristocetin and that of asialo-vWF with GPIb while it partially blocked botrocetin-mediated interaction of vWF to GPIb. The inhibitor reacted with native vWF, the 39/34 kDa fragment (amino acids [aa] 480/ 481-718) and the recombinant vWF fragment (MalE-rvWF508-704), but not with Fragment III-T2 (heavy chains, aa 273-511; light chains, aa 674-728). A synthetic peptide (aa 514-542) did not inhibit vWF-inhibitor complex formation. We conclude that this is the first auto-antibody of class IgG from human origin that recognizes the sequence in the A1 loop of vWF, resulting in a virtual absence of functional vWF and a concomitant severe bleeding tendency although recognition site is different from the residues 514-542 which is crucial for vWF-GPIb interaction.

Adult↗
PubMed1997

Upregulation of interferon-alpha receptor expression in hydroxyurea-treated leukemia cell lines.

BACKGROUND: Interferon-alpha (IFN-alpha) shows its antitumor effect through binding to specific cell surface receptors. A DNA synthesis inhibitor, hydroxyurea (HU), has been successfully combined with IFN-alpha to improve the efficiency of IFN therapy for chronic myelogenous leukemia (CML). To understand the mechanism of this combination effect, expression of IFN-alpha receptors on the CML cell line, K562, was studied before and after treatment with HU. METHODS: Cells were treated with HU at a dose of 0, 0.1, 0.2, or 0.4 mmol/L for 48 hours. Binding assays were performed using 125I-labeled IFN-alpha at 4 degrees C. Cell cycle analysis was carried out using flow cytometer following staining cellular DNA with propidium iodide. Northern blot analysis was performed to evaluate the inducibility of interferon regulatory factor-1 (IRF-1) gene expression by IFN-alpha. RESULTS: Hydroxyurea-treated cells showed a dose- and time-dependent increase in binding of 125I-labeled IFN-alpha (maximal 2.5-fold). The increase of binding was caused by an increase in the number of binding sites with a constant receptor affinity. Similar results were obtained in the Burkitt's lymphoma cell line, Daudi. Cell cycle analyses suggested that upregulation of the IFN receptor may have occurred as a result of the alteration in the cell cycle distribution. Furthermore, IFN-alpha induction of the IFN-inducible gene IRF-1 mRNA in HU-treated K562 cells was 2-fold higher than that in untreated cells. CONCLUSIONS: Thus, HU may have an ability to enhance the response to IFN-alpha probably because of its ability to upregulate the IFN-alpha receptors, suggesting that this may be involved in the mechanism of effective combination therapy of IFN-alpha with HU.

Antineoplastic Agents↗
PubMed1997

[A mesenchymal malignant mesothelioma that changed from mixed type to purely sarcomatous type].

A 65-year-old man was admitted to the hospital because of an abnormal shadow on a chest roentgenogram. A diagnosis of mixed-type malignant mesothelioma was made after transcutaneous needle biopsy and thoracoscopic biopsy. The tumor was considered to be inoperable because it had diffusely invaded surrounding tissue, and therefore the patient was treated with chemotherapy only. About one year later, he died of acute pneumonia. At autopsy, a mesenchymal malignant mesothelioma that did not have an epithelial component was found. We know of no previous report of a case in which a tumor with a biopsy-proven epithelial component apparently changed to a purely sarcomatous type. No satisfactory explanation for this phenomenon has been offered.

Aged↗
PubMed1997

[Peripheral carcinoid tumor of the lung presenting as a solitary mass shadow on a chest roentgenogram and diagnosed by CT-guided percutaneous needle biopsy].

A 59-year-old woman was referred to our clinic because a solitary mass shadow (2.5 cm in diameter was seen in the left lower lung field on a chest roentgenogram. Transbronchial biopsy via a fiberoptic bronchoscope did not yield a definitive diagnosis. Examination of a specimen obtained by CT-guided percutaneous needle biopsy revealed that the tumor consisted of small cells proliferating in a solid, tubular, pseudoglandular, and follicular pattern, which suggested the diagnosis of carcinoid. A left lower lobectomy was performed, and several hilar and mediastinal lymph nodes were also removed. The tumor cells did not show pleomorphism of nuclei, mitotic activity, or necrosis. Grimelius and immunohistochemical stains for chromogranin. A, neuron-specific-enorase, synaptophysin, and serotonin were positive. These findings confirmed the diagnosis of carcinoid CT-guided percutaneous needle biopsy can be useful for the diagnosis of peripheral carcinoid and other peripheral lung tumors.

Biopsy, Needle↗
PubMed1997

[Efficacy of the TURBO-fluid attenuated inversion recovery spin echo sequence of MRI as a preoperative neuroradiological examination].

Whenever the extirpation of intracranial tumors is planned, neurosurgeons always keep their eyes on the cerebrospinal fluid (CSF) space around intracranial tumors. If enough space exists in the neighborhood of the tumors, the damage to adjacent parenchyma may be reduced by the procedure through the CSF space. A newly advanced MRI pulse sequence: the FLAIR (fluid attenuated inversion recovery) imaging, in which a long TE spin echo sequence is used with suppression of the CSF with an inversion pulse, displays the CSF space as a no-signal intensity area. There have been only a few reports, however, on the FLAIR pulse sequence of brain tumors as yet. We examined 34 cases of intracranial tumors by FLAIR images and analyzed the advantages and disadvantages of the FLAIR pulse sequence for decision making on tumor removal. Making use of the FLAIR pulse sequence, the CSF space is depicted as a no-signal intensity area and much more information about perifocal edema and the invasion area around the tumors can be provided than that provided by the other ordinary pulse sequences (T1 weighted images, T2 weighted images and Proton weighted images). Therefore, operative strategies can be more easily worked out on the FLAIR images. Furthermore, the difference between arachnoid and epidermoid is able to be detected on the FLAIR images. Nevertheless, on FLAIR images, the tumors without perifocal edema or invasion to adjacent parenchyma were not apparent and the difference between tumoral dissemination into multi-ventricular space and the periventricular artifact of FLAIR images could not be distinguished. The FLAIR pulse sequence has other artifacts like intraventricular flow related enhancement and so on. If the images are carefully checked up on the above-mentioned points, the FLAIR pulse sequence of MRI can not fail to be useful in making plans for operations on intracranial neoplasms.

Adult↗
PubMed1997

[Successful treatment of subdural hematoma with operation in a patient with acute promyelocytic leukemia].

A 51 year-old male admitted with petechiae and headache. Acute promyelocytic leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed. He received all-trans retinoic acid (ATRA) with enocitabine and daunomycin for induction chemotherapy, and supportive therapy for DIC. On 2nd day after admission, subacute subdural hematoma was confirmed with CT scan. He had anisocoria and disturbance of consciousness, and was treated with neurosurgical operation for his life saving on the 3rd day. Although DIC was continued at this time, the operation was done without problem. The recurrence of hematoma has not occurred after the operation. Furthermore, the findings of DIC disappeared by the day 6 following induction therapy. He achieved a complete remission including cytogenetic findings on 35th day after administration of ATRA and received 3 times of combination chemotherapy as consolidation therapy. It may be difficult to do neurosurgical treatment in the setting of DIC. However, we should consider whether the indications for surgery operation according to the condition of each patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Efficacy of chemotherapy for clear cell adenocarcinoma of the ovary].

In line with various protocols for chemotherapy of ovarian carcinoma, we used EP (etoposide-cisplatin or carboplatin) therapy in 10 patients with clear cell adenocarcinoma as the first line chemotherapy. Four of these cases were in advanced stage at IIIc, and had residual tumor after the operation. One of these patients with measurable tumor responded to semi-high dose treatment, and 5-days of continuous infusion of etoposide resulted in CR. Three cases of a patient at the stages of Ic and IIc are in disease free status after two years of standard-dose EP therapy. Therefore, high-dose EP therapy might be an effective chemotherapy for some patients with ovarian clear cell adenocarcinoma.

Adenocarcinoma, Clear Cell↗
PubMed1997

[Adenocarcinoma of the lung associated with acute promyelocytic leukemia and miliary tuberculosis].

A 44-year-old man was admitted to the hospital because of acute promyelocytic leukemia. A nodular shadow (2.5 cm in diameter) was seen in the right upper lung field on a chest roentgenogram. During the administration of combination chemotherapy for the leukemia, diffuse granular shadow appeared in all lung fields. Transbronchial lung biopsy findings indicated tuberculosis. The patient was given streptomycin, isoniazid, rifampicin and ethambutol, but the nodular show enlarged and a pleural effusion appeared on the right side. Cytologic examination of the pleural effusion revealed adenocarcinoma. Similar findings were obtained from a second transbronchial lung biopsy. The frequency of association of lung cancer and other malignancy is about 4%. The incidences of primary lung cancer found during the course of active tuberculosis, active pulmonary tuberculosis found during the course of primary lung cancer, and tuberculosis found during the course of acute leukemia are 0.9 to 1.4%, 0.4 to 4.3%, and 2.4 to 4.5%, respectively. To our knowledge, this is the first case in Japan in which adenocarcinoma of the lung was associated with acute promyelocytic leukemia and tuberculosis.

Adenocarcinoma↗