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Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 397 records · Page 22Linked to original sources

Cell-cycle-associated expressions of proliferating cell nuclear antigen and Ki-67 reactive antigen of bone marrow blast cells in childhood acute leukemia.

To investigate the growth characteristics of human leukemia cells, the expression of proliferation-associated nuclear antigens was examined in relation to cell cycle phases in marrow blast cells obtained from 37 untreated children with acute leukemia. Ki-67 monoclonal antibody reactive antigen and proliferating cell nuclear antigen (PCNA) were measured by the simultaneous flow cytometric analysis of DNA and nuclear antigens. The percentage of PCNA-positive cells was always higher than that of Ki-67-positive cells in individual patients. The level of PCNA was greatly increased in G1 or early S phase, but was generally stable in S and G2 phases. Accordingly, most of the cells in the proliferative compartments (greater than 2C DNA) showed a high expression of PCNA. In contrast, expression of Ki-67 antigen varied greatly from patient to patient, and differed significantly in different subtypes of the disease. The level of Ki-67 antigen increased with the cell cycle progression, showing maximum expression in late S and G2 phases. However, in most of the patients, a distinct population of Ki-67-negative cells was found not only in G1 phase, but also in the proliferative compartments. These results appear to reflect differences in the proliferative activity of bone marrow blast cells in childhood acute leukemia.

Cell Cycle↗

[Detection of circulating activated platelets by anti-GMP-140 monoclonal antibodies].

The clinical significance and detection methods for circulating activated platelets are reviewed. It has been recently demonstrated that three kinds of platelet granules, dense granule, alpha-granule and lysosome, have specific membrane proteins; granulophysin, GMP-140 (PADGEM) and CD63 antigen, respectively, and that these specific granule-membrane proteins become exposed on the surface of the activated platelets. It is believed that detection of circulating activated platelets, using monoclonal antibodies specific to these granule-membrane, may be reliable and diagnostic value in thrombotic and prethrombotic diseases. Preliminary clinical studies using 2T60, a newly developed anti-GMP-140 monoclonal antibody, was presented.

Antibodies, Monoclonal↗

[Overt leukemia from MDS associated with marked basophilia].

A 52-year-old woman was admitted to our hospital because of leukocytosis. She had been diagnosed with RAEB in another hospital in past time. At the admission, the white cell count was 30,900/microliter with blasts (14.0%) and marked basophilia (49.0%). Bone marrow aspiration revealed with 30.2% blasts and 21.1% basophils. Having obtained those results, diagnosis of RAEB in transformation was made. After admission, number of basophils in peripheral blood increased gradually, and level of histamine in serum was elevated significantly. Multiple peptic ulcers in stomach and bowel and high fever were induced due to histaminemia. Despite several therapy she died because of respiratory failure and septisemia. Although the mechanism of basophilia in this patient could not be clarified, there was a possibility that basophilia in this patient might be differentiated from leukemic clone because almost basophils in peripheral blood were mature and those had many granules including metachromasia by stained with toluidine blue.

Basophils↗

[Clinical significance of the click intervals for the diagnosis of dysfunction of the Medtronic-Hall prosthetic valve].

To investigate the clinical significance of click interval for evaluation of prosthetic valve dysfunction, 20 patients underwent Medtronic-Hall (MH) valve replacement (14 in the mitral position and 6 in the aortic position) were studied by simultaneous high-speed recordings of phonocardiogram, echocardiogram and/or Doppler echocardiogram. Two of the 20 patients, one in the mitral and the other in the aortic position, showed MH valve dysfunction. Eleven patients with normally functioning Björk-Shiley (BS) valve in the mitral position served as controls. Results were as follows: 1. There were usually 3 opening clicks (OC1, OC2, OC3) in patients with normally functioning MH valve in the mitral position. These 3 clicks coincided in timing with the beginning of opening, maximum opening and the end of sliding motion, respectively. Both OC1 and OC2 of the MH valve occurred in similar timing with those of the BS valve (A2-OC1 interval: MH = 65.4 +/- 11.8 msec vs BS = 72.3 +/- 17.2 msec; OC1-OC2 interval: MH = 31.2 +/- 7.7 msec vs BS = 27.3 +/- 6.1 msec). However, OC3 occurred significantly later in MH valve than in the BS valve (OC2-OC3 interval: MH = 32.3 +/- 7.5 msec vs BS = 16.4 +/- 3.8 msec, p < 0.01). 2. There were 2 closing clicks (CC1, CC2) in normally functioning the MH valve in the aortic position. These 2 clicks coincided in timing with the beginning and the end of the closing motion, respectively. Mean value of CC1-CC2 interval in 5 prosthetic patients with normal function was 31.0 +/- 9.6 msec. 3. A patient with malfunctioning MH valve in the mitral position showed a markedly prolonged OC1-OC2 interval, ranging from 66 to 140 msec, and she had multiple diastolic clicks after the OC2 phase. Prolonged OC1-OC2 interval was mainly caused by the delay of appearance of OC2, and it was thought to be due to temporary limitation of opening motion of the valve by valve thrombosis. 4. A patient with malfunctioning MH valve in the aortic position showed a markedly prolonged CC1-CC2 interval (100 msec), and he had a significant severe aortic regurgitation during this phase. At operation, fibrinoid thrombus was attached to the aortic annulus at the side of minor orifice of the valve. Closing motion of the valve was disturbed by this thrombus, and the completion of valve closure was markedly delayed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Mitral valve prolapse associated with partial absence of commissural chordal insertion: report of two cases].

We reported 2 cases of mitral valve prolapse (MVP) associated with partial absence of the chordae tendineae. Case 1 was a 25-year-old man who was admitted to our hospital for further examinations of an apical pansystolic murmur (Levine 4/6) and the abnormal shadow on his chest radiograph. He was diagnosed as having grade 3 + mitral regurgitation (MR) by the Sellers classification and pulmonary varix by cardiac catheterization. Transesophageal echocardiography revealed MVP of the rough zone of the anterior mitral leaflet and MR blowing into the pulmonary varix. Case 2 was a 60-year-old man who was admitted to our hospital because of congestive heart failure and apical pansystolic murmur (Levine 4/6). Parasternal echocardiography revealed prolapse of both the anterior and posterior mitral leaflets and moderate MR. In both cases, absence of insertion of anterolateral commissural chordae was confirmed after surgery, and the abnormalities of chordal arrangement and insertion were considered as causes of MVP in these cases.

Adult↗

[A case of interstitial pneumonitis associated with polymyositis complicated by renal cell carcinoma].

A 55-year-old woman was referred to the department of urology in our hospital with left renal tumor, discovered during examinations at another hospital for fever and dyspnea on exertion. Because surgery was difficult due to severe hypoxemia, pulmonary function impairment (restrictive) and bilateral diffuse interstitial shadows on chest X-ray film, the patient was referred to our department. Interstitial pneumonitis was found on transbronchial lung biopsy, and serum GOT, LDH and CPK values were elevated. These symptoms and abnormalities of laboratory data were improved by administration of prednisolone 60 mg/day, and left nephrectomy was performed without any complications. Pathological examination of the surgical specimen showed clear cell carcinoma (Grawitz). Steroid therapy was tapered off and her clinical course was good. Six months after surgery, the patient developed a recurrence of fever, which was not responsive to antibiotics. Polymyositis was diagnosed on the basis of elevated serum GOT, LDH and CPK, electromyogram and muscle biopsy findings and positive anti-Jo-1 antibody. Polymyositis/dermatomyositis is sometimes associated with interstitial pneumonitis or malignant neoplasms, but rarely with both simultaneously. Moreover, renal cell carcinoma is very rare among the malignant neoplasms associated with polymyositis/dermatomyositis, and we therefore report this unusual case.

Antibodies, Antinuclear↗

[Fluorescence polarization immunoassay of isepamicin in blood spotted on filter paper].

A simple method has been developed for the determination of the aminoglycoside antibiotic isepamicin (ISP) in whole blood, using dried blood spots (DBSs) on filter-paper. ISP in the DBSs were recovered most effectively in 0.5 M Na2HPO4-NaH2PO4 buffer (pH 7) by incubation for 30 minutes at 35 degrees C in an ultrafiltration tube. The eluates from the DBS papers were centrifuged at 3,000 x g for 10 minutes. The clear, colorless filtrates were transferred to an Abbott TDx cartridge for measurement by the fluorescence polarization immunoassay. The lower limit for the quantitative determination of ISP in the DBS was 2.5 micrograms per ml of whole blood. The method permits a simple collection of blood at a microliter level and should prove particularly useful for therapeutic drug monitoring of ISP in blood at effective levels in pediatric and geriatric patients.

Animals↗

[An attempt at intraoperative, ultrasound-guided microwave tissue coagulation for metastatic liver tumors].

Using a microwave tissue coagulator, we attempted intraoperative, ultrasound-guided cauterization and thermocoagulation of metastatic liver tumors. The procedure, safety and efficacy of this therapy were analyzed. During the past 2 years, this therapy was used in 10 patients with unresectable metastatic liver tumors. During surgery, monopolar electrodes were inserted with an ultrasonic guide. One round of cauterization lasted for 10 seconds at 100 W. It was repeated until the tissue around the tumor became hyperechoic. This therapy was used for 67 tumor lesions in total (2-22 lesions/patient). No complications were observed during or after this therapy, except for a case complicated by liver abscess. The anti-tumor effect of the therapy was assessed by histological examination of resected liver tissues. Tumor coagulation and necrosis were observed consistent with the cauterized area. The response to this therapy, assessed by diagnostic imaging, was CR (complete remission) in 3 cases, PR (partial remission) in 3, NC (no change) in 3 and PD (progressive disease) in 1. Thus, the efficacy (the percentage of cases showing CR or PR) was 60%. Since this therapeutic approach acts directly on tumors and is simple and safe, it seems to provide a useful means for intraoperative regional treatment of tumors.

Adult↗

[Current progress in cancer chemotherapy for childhood cancer].

New strategies in antineoplastic therapy that have been applied during the last 5 years to children with malignant disease include the Goldic-Coldman hypothesis, new methods of drug delivery, reduction in toxicity with prolonged intravenous infusions, shortening of maintenance therapy and techniques to improve the compliance of adolescents and older children with prescribed therapy. These new concepts of chemotherapy in developmental pharmacology to treat cancers in children are reviewed.

Animals↗

[Effects of endotracheal intubation on the trachea--usefulness of the evaluation by MRI].

Using an MRI apparatus, we observed the effects of endotracheal intubation on the trachea by measuring T1 value before and after an operation in ten surgical cases. T1 value of the anterior wall at the level of the first tracheal ring was 275.8 +/- 58 msec, and that of the posterior wall was 346.8 +/- 72 msec. The patients were all intubated under general anesthesia. Anesthesia was maintained with inhalation anesthesia such as nitrous oxide-oxygen-enflurane with the aid of vecuronium bromide. Periods of intubation varied between 80 to 46 minutes, and averaged 270 +/- 112 minutes. After the extubation, T1 value showed 312 +/- 62 msec at the anterior wall and 395 +/- 82 msec at the posterior wall. In the case of the posterior wall, T1 value was significantly prolonged compared with that of the pre-intubation period. Prolongation of T1 value is assumed to be related to the increase of tissue free water demonstrating the occurrence of tissue edema. From the findings that T1 value might be prolonged by endotracheal intubation, we conclude that the MRI apparatus is useful for investigating the effects of the intubation procedure on the trachea.

Adult↗

In vitro properties of the newer quinolones.

Table 5 summarizes the activity of the newer quinolones against various bacteria including intracellular bacteria and the other microorganisms. In this table, the overall MIC ranges of NFLX, ENX, OFLX, and CPFX, for susceptible isolates of each bacteria are schematically presented. The newer quinolones are considered to have sufficient activity against gram-negative enteric bacteria, N. gonorrhoeae, and H. influenzae and Legionella spp. Since OFLX and CPFX show only moderate activity against staphylococci, streptococci, and P. aeruginosa, improvement is expected. As shown in Table 3, TFLX and the recent investigational quinolones such as SPFX and KB-5246 show higher and promising activity against gram-positive bacteria. However, further studies are needed with longer periods to indicate whether these newer agents will be able to stop the increase of quinolone-resistant staphylococci. Furthermore, the activity of the newer quinolones against obligate anaerobes such as clostridia and bacteroides are considered to be insufficient for clinical use. Whether it will be possible to synthesize quinolones with anti-anaerobic activity sufficiently for clinical treatment is uncertain. Although Mycobacterium tuberculosis is susceptible to the newer quinolones, other mycobacteria are somewhat less susceptible to this class of agents. In addition, the newer quinolones have adequate activity against mycoplasma, chlamydia and rickettsia. From a microbiological viewpoint the prospects for the newer quinolones would be primarily to find agents that have higher anti-staphylococcal and anti-streptococcal activity. Secondly, agents possessing superior activity against obligate anaerobes such as Bacteroides spp. and Clostridium spp. are expected to synthesize. Furthermore, it may be possible to synthesize compounds that are sufficiently active for clinical use against atypical mycoplasma, chlamydia, and rickettsia.

4-Quinolones↗

[Differentiation therapy of acute promyelocytic leukemia: two successful cases of remission induction by all-trans retinoic acid].

We described two pediatric patients with acute promyelocytic leukemia (APL) who were successfully induced into complete remission with all-trans retinoic acid (ATRA, 45 mg/m2 per day) after failing on conventional chemotherapy. Initial response was observed as correction of DIC within a week of treatment. Hematologically, initial increase of maturing leukocytes reached a peak peripheral WBC count on the 16th and 20th day, respectively. However, these seemingly differentiated leukocytes retained Auer body and dysplastic features and there was no concomitant recovery of erythroid and megakaryocytic lineages at this point. A sudden drop of leukocyte counts after this peak made a brief period of leukopenia before the complete remission was finally attained morphologically in 4-5 weeks. Thus, remission of APL by ATRA therapy consisted of a two-phase course. In one patient, we observed an increase of histiocytes phagocytizing leukocytes in the marrow during the recovery from leukopenia. It is, therefore, postulated that the two-phase course of recovery may reflect the differentiation of leukemic cells by ATRA and subsequent clearance of senescent cells by the reticuloendothelial system followed by regeneration and differentiation of residual normal hematopoietic stem cells.

Adolescent↗

Misoprostol accelerates colonic mucosal repair in acetic acid-induced colitis.

The objectives of this study were 1) to determine whether misoprostol (MISO) (prostaglandin E1 analog) pretreatment protects the colonic mucosa from the injurious effects of acetic acid by attenuating the initial injury or by enhancing the rate of repair and 2) to assess the relationship between the protective effect of MISO pretreatment and mucosal ornithine decarboxylase activity in the inflamed colon. We found that the intrarectal administration of acetic acid caused rapid and extensive injury to the colonic mucosa, such that mucosal permeability increased 88-, 75-, 26-, 7.5- and 9.3-fold at 1, 2, 6, 24 and 48 hr after the enema, respectively. Intrarectal pretreatment with 50 micrograms of MISO for 30 min did not attenuate the increase in mucosal permeability at 1 hr after enema; however, it did significantly reduce mucosal permeability by 50 to 60% at 2, 6 and 48 hr after enema. We also demonstrated that acetic acid produced an 8.4-fold increase in colonic myeloperoxidase activity and a 1.8-fold increase in colonic weight at 48 hr after enema. MISO significantly reduced the increases in both myeloperoxidase activity and colon weight. Ornithine decarboxylase activity in the descending colon of vehicle-pretreated animals increased significantly only at 24 hr after the acetic acid enema. In addition, MISO pretreatment followed by acetic acid enema resulted in significantly higher ornithine decarboxylase activities in the descending colon at 2 and 6 hr, compared with the vehicle plus acetic acid and MISO plus saline groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Distributional change of fodrin in the wound healing process of the corneal epithelium.

Distribution of fodrin, F-actin, and E-cadherin in the wound healing process of the mouse corneal epithelium was examined by immunolabeling techniques. In the normal epithelium, fodrin, F-actin, and E-cadherin were observed only in the cell periphery. After wounding, however, fodrin was observed diffusely in the basal cell cytoplasm. Distribution of the other two proteins was not changed. Fodrin in the upper cell layers did not show cytoplasmic labeling. The distributional change of fodrin in the basal cell was seen not less than 1 mm apart from the wound edge and as early as 5 min after the wounding, lasted for about 12 hr, and then gradually disappeared. The change in fodrin localization is one of the earliest phenomena which occur in the corneal epithelium after wounding. Because fodrin is an actin-binding protein and is believed to interact with E-cadherin, this change may be important in modulating the cytoskeleton and the intercellular junction before cell migration occurs.

Actins↗

Functional Ca2+ channel produced by purified platelet membrane glycoprotein IIB-IIIA complex incorporated into planar phospholipid bilayer.

The ability of the platelet membrane glycoprotein (GP) IIb-IIIa complex to function as a Ca2+ channel was investigated by electrophysiological methods. The GPIIb-IIIa complex was purified with an electrically silent detergent, CHAPS, and reconstituted into liposomes. After incorporation of these liposomes to a planar phospholipid bilayer, Ba(2+)-permeable channel currents were detected. Since neither residual detergent nor dissociated GPIIb and IIIa produced any currents, the observed channel currents were attributed to the GPIIb-IIIa complex. These channel currents showed similar electrical properties with the Ca2+ channel previously described in platelet plasma membrane; a single channel conductance of approximately 10 pS in 53 mM Ba2+ solution and voltage-independency. It was concluded that the purified GPIIb-IIIa complex can act as a divalent cation-permeable channel in the artificial phospholipid bilayer.

Calcium Channels↗

Electrophysiological evidence that glycoprotein IIb-IIIa complex is involved in calcium channel activation on human platelet plasma membrane.

The involvement of platelet glycoprotein (GP) IIb-IIIa complex in calcium channel activity on the plasma membrane was investigated using an electrophysiological approach. Plasma membrane vesicles were prepared from thrombin-stimulated platelets and incorporated into planar lipid bilayers. Voltage-independent Ca2+ channel currents with a conductance of about 10 pS (in 53 mM Ba2+) were observed, in membranes derived from thrombin-stimulated, but not unstimulated platelet membranes. These channel activities were markedly reduced by exposure of membranes to EGTA at 37 degrees C. This reduction was specifically related to the dissociation of the GPIIb-IIIa complex since preincubation of the membranes with a monoclonal antibody to the GPIIb-IIIa complex (AP-2) could protect the channel activities from the effect of EGTA. Thrombasthenic platelets, which lack the GPIIb-IIIa complex, showed impaired channel activities characterized by decreased open probability and lowered conductance states. Furthermore, when platelets were stimulated by thrombin in the presence of EGTA, AP2, or the synthetic peptide RGDS, to prevent fibrinogen binding to the GPIIb-IIIa complex, open probabilities of the channel currents in these membrane vesicles were also decreased. These results suggest that the GPIIb-IIIa complex is involved in platelet Ca2+ channel activation and that ligand binding to the complex during platelet activation may modify the activation of Ca2+ channels.

Amino Acid Sequence↗