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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 433 records · Page 24Linked to original sources

Influence of monocyte-macrophage lineage cells on alkaline phosphatase activity of developing osteoblasts derived from rat bone marrow stromal cells.

We have studied the osteogenic changes of the marrow stromal cells cultured from bone marrow cells of Wistar rats. After the stromal cells became confluent, several clusters of cuboidal cells appeared. These cuboidal cells showed strong alkaline phosphatase (ALP) activity and revealed some osteoblastic features electron-microscopically. In the culture, monocyte-macrophage-lineage cells (MMLC) proliferated in contact with the stromal cells. The MMLC exist near the bone cells in vivo. Yet the exact role of the MMLC is not clear. In order to evaluate how the MMLC influence the stromal cells, the ALP activity of the stromal cells in the culture condition containing a large number of MMLC (group A) was compared with that in the condition in a small number of MMLC (group B). The ALP activity in group A (11.28 +/- 1.04 Units/mg protein) was significantly higher than that in group B (6.58 +/- 0.38 Units/mg protein). This suggests that the MMLC stimulate the osteogenic differentiation of the stromal cells.

Alkaline Phosphatase↗

[Relationship between limitation of daily life and prognosis in patients with sequelae of tuberculosis treated with long-term oxygen therapy].

The sequelae of tuberculosis (TBC) sometimes causes severe restrictive lung disorders. In Japan, lung tuberculosis was pandemic up to the 1950s, with TBC being a major underlying disease of chronic respiratory failure and cor pulmonale. Until the end of 1991, we encountered 95 cases of Home Oxygen Therapy (HOT) in Ogaki area, 30 of which were patients with TBC. To clarify factors affecting the prognosis of these patients, we examined background factors, directing special attention to daily activities. In this study, 10 inactive patients (Group A) whose daily activity was limited to indoors and 10 control patients (Group B) whose age, vital capacity and arterial PO2 were equal to inactive patients, from the 30 TBC cases were used. A comparison was made of the prognoses. Among the patients, activity was closely related to dyspnea grade and arterial PCO2. Group A patients showed more marked dyspnea and lower arterial PCO2 than those of group B patients. Percentage home stay and cumulative survival rates of Group A patients (percentage home stay, 59.2 +/- 38.7% and 3 year survival, 26.3%) were significantly less than those of Group B patients (91.0 +/- 16.4% and 87.5%, p < 0.05, respectively). Among chronic pulmonary emphysema patients treated with HOT, no significant relation between activity and prognosis could be found, when factors of age, arterial PO2 and forced expiratory volume in 1 sec were excluded. There would thus appear to be a close relation between activity and prognosis in TBC patients specific for underlying disease.

Activities of Daily Living↗

[A case of drug induced pneumonitis caused by oral etoposide].

We report a case of drug induced pneumonitis caused by oral etoposide. A 63-year-old man was admitted to our hospital in August 1991 because of low grade fever and dyspnea. He underwent right upper lobectomy on Nov. 27th, 1990 for lung cancer (squamous cell carcinoma), and courses of adjuvant chemotherapy (CBDCA, IFX, etoposide) during the following admission period. He was discharged on Feb. 14th, 1991, and as an outpatient, oral etoposide (25 mg/day) was administered for about 7 months (6,125 mg in total). Chest X-ray film on admission showed reticulonodular shadows in bilateral lung fields, and computed tomography showed diffuse interstitial shadows. Blood gas analysis showed marked hypoxemia (PaO2 breathing room air was 48.4 Torr). Transbronchial lung biopsy revealed edema of the alveolar walls and marked proliferation of type II alveolar epithelial cells, suggesting cytotoxic reaction. After termination of etoposide administration and following steroid pulse therapy, both clinical symptoms and hypoxemia were ameliorated. To our knowledge, this is the first report of etoposide-induced pneumonitis.

Administration, Oral↗

[Prediction of performance status after pneumonectomy].

To predict performance status (P.S.) following pneumonectomy, patients with lung carcinoma underwent pre-surgical pulmonary function tests with spirometry and unilateral pulmonary artery occlusion test (UPAO test). Between 1980 and 1991, twenty-nine patients who had survived more than six months after surgery were selected for the study. These patients were divided into two groups according to P.S. measured at six months after surgery: 16 patients with P.S. 0 to 1 were in Group A, and 13 patients with P.S. 2 to 3 were in Group B. The results of the following tests obtained prior to surgery were compared for the two groups to predict post-surgical P.S.; vital capacity (VC), VC/m2, forced expiratory volume in 1 second (FEV1.0), FEV1.0/m2, predicted VC/m2 and predicted FEV1.0/m2 calculated with residual pulmonary segments, mean pulmonary arterial pressure (PPA) before UPAO and 15 minutes after UPAO, total pulmonary vascular resistance (TPVR) before and during UPAO, and rate of changes in PPA and TPVR. Results obtained were as follows: Group B demonstrated significantly higher TPVR (p < 0.05) before the UPAO, PPA (p < 0.05) and TPVR (p < 0.002) during UPAO, and rate of change in TPVR (p < 0.02) than those in Group A. There were no significant differences between the two groups for other test results. From these results, lowering of post-surgical P.S. might be predicted when the TPVR during UPAO was 350 dyne.sec.cm-5/m2 or more.

Blood Pressure↗

Immunohistochemical, quantitative immunoelectron microscopic, and DNA cytofluorometric characterization of chemically induced rat malignant fibrous histiocytoma.

Malignant fibrous histiocytoma (MFH) was induced in rats by injection of 9,10-dimethyl-1,2-benzanthracene. Using cell suspensions prepared from the heterotransplanted nude mouse tumor as immunogen, a monoclonal antibody, (MAb), MEP-1, against fibroblastlike MFH tumor cells was generated. In the primary rat tumors and transplanted rat or nude mouse tumors, MEP-1 reacted specifically with the fibroblastlike cells but not with the histiocytelike cells or xanthoma cells. Anti-rat macrophage MAbs RM-1 and TRPM-3 did not stain the fibroblastlike cells, but both were reactive with the histiocytelike cells. Double stainings with both MEP-1 and RM-1 or TRPM-3 did not detect any double positive cells. Immunoelectron microscopy using these MAbs showed that the fibroblastlike cells were the major cell component of the primary and transplanted rat tumors and that their cell membrane was stained positively with MEP-1, but not for RM-1 or TRPM-3. By the double staining method using a MAb against prolyl 4-hydroxylase beta and MEP-1 or TRPM-3, this enzyme was demonstrated in MEP-1-positive cells but not in TRPM-3-positive cells. Results obtained by DNA cytofluorometry with 4,6-diamidino-2-phenylindole dihydrochloride staining or by the combined method of DNA cytofluorometry and indirect immunofluorescence, using MEP-1, RM-1, and TRPM-3, indicate that MEP-1-positive cells are neoplastic cells of rat MFH having proliferation activity. In the transplanted nude mouse tumors, no differentiation of MEP-1-positive rat tumor cells into histiocytelike cells was detected, and all histiocytelike cells were immunostained by F4/80 and most of them were positive for M5/114. These results suggest that fibroblastlike cells and intermediate cells are tumor cells of 9,10-dimethyl-1,2-benzanthracene-induced rat MFH showing differentiation toward fibroblasts and that histiocytelike cells are infiltrated macrophages.

9,10-Dimethyl-1,2-benzanthracene↗

Ultrastructural changes of collagen fibers in the anterior cruciate ligament of bipedal rats after enforced running.

The effect of enforced running on the morphological characteristics of the fibroblasts and on the distribution of the collagen fibril diameter in the anterior cruciate ligament of bipedal rats was examined by electron microscopy. Twelve bipedal rats were divided into two groups of equal numbers: (1) those without exercise, and (2) those with enforced exercise on a treadmill for four weeks. Ninety percent of the fibroblasts in the rats without exercise were ovoid-shaped with a round nucleus, whereas eighty-one percent of those in the rats with exercise were spindle-shaped with indented nucleus. There was a significant difference in the ratios of ovoid-shaped to spindle-shaped cells between the two groups (p < 0.05). There was an increased number of rough surfaced endoplasmic reticula and lysosomal vesicles in the fibroblasts of the rats with exercise. The collagen fibril diameters of the rats with exercise varied in size from 20 to 120 nm, while those of the rats without exercise were uniform in size, mostly between 50-80 nm. Mean collagen fibril diameter was 70.8 +/- 16.6 nm in the rats without exercise, and 66.6 +/- 21.9 nm in the exercised rats. This difference was significant (p < 0.05). These electron-microscopical findings indicate an increased collagen metabolism in the anterior cruciate ligament of rats with enforced running.

Animals↗

[A case of chest wall abscess due to Salmonella newport].

A 18-year-old female with a history of precordial pain was admitted. There was a mass (3.5 x 2.5 cm) in the right inframammary region which was suspected to be chest wall tumor on the basis of CT scan and Ga scintigraphy findings. Exploratory surgery, consisting of total resection of the tumor without removing the ribs, was performed and revealed an abscess. Culture of pus from the abscess grew Salmonella newport (0 antigen 8, H antigen eh; 1.2). Focal infection with Salmonellosis is discussed. Surgical treatment is necessary in addition to chemotherapy.

Abscess↗

[Spontaneous splenic rupture in a case of non-Hodgkin's lymphoma].

A 58-year-old man admitted to hospital as an emergency with pain in the left hypochondrium. The initial physical examination revealed hypotension, giant splenomegaly and ascites but no lymphadenopathy was found. Laboratory findings at admission included hemoglobin level of 9.2g/dl, leucocyte count of 22, 100/microliters with 2% of lymphoma cell and platelets count of 66,000/microliters. A presumptive diagnosis of ruptured spleen was made. Splenectomy was performed after 7 hours from admission. The spleen was infiltrated by malignant lymphoma. Three weeks after surgery, left neck and abdominal lymphoadenopathy were recognized, therefore systemic chemotherapy was started. The leukemic change was one of important factors for the mechanisms of spontaneous splenic rupture in malignant lymphoma.

Antineoplastic Agents↗

[Kimura's disease (eosinophilic lymphfolliculoid granuloma)].

Eosinophilic lymphfolliculoid granuloma was first described by Kimura et al. under the heading of "On an unusual granulation accompanied by hyperplastic changes of lymphatic tissue" in 1948. There after various terms have been used for this disease, such as eosinophilic granuloma and eosinophilic lymphfolliculosis. Ever since Iizuka et al. proposed the term Kimura's disease in 1959. This disease is a relatively rare condition. It usually occurs in the soft tissue of the head and neck regions and extremities, associated with eosinophilia and elevation of serum IgE. The main histopathological features are proliferation of lymphfolliculoid structures, granulation tissue with marked infiltration of eosinophiles and mast cells, and fibrosis. The etiology of this condition is, however, still unknown. We report the clinicopathology and immunohistochemical study of this disease.

Adolescent↗

Novel function of C4a anaphylatoxin. Release from monocytes of protein which inhibits monocyte chemotaxis.

The complement C4-derived anaphylatoxin, C4a, possesses a strong chemotaxis inhibitory capacity to blood monocytes at concentrations as low as 10(-16) mol/L. In our study, treatment with carboxypeptidase B to convert it to C4a des Arg77 decreased the inhibitory activity to less than 1/1,000. The extraordinary inhibitory capacity of C4a suggests the presence of an amplification mechanism in this inhibition. Indeed, we found that the conditioned media of peripheral blood mononuclear cells or monocyte/macrophage lineage cell lines (U937 and THP-1 cells) preincubated with 10(-16) mol/L C4a for 5 minutes or more at 37 C possessed the inhibitory capacity 100,000-fold stronger than the original activity of C4a. The monocyte-derived chemotaxis inhibitory factor seemed monocyte-specific. This cell-derived factor was sensitive to treatment with trypsin and chymotrypsin and immunologically distinct from C4a. The apparent molecular size of the monocyte factor was estimated to be approximately 20 kd by gel filtration. These results indicate that C4a anaphylatoxin induces the release from monocytes of a protein with inhibitory activity for monocyte chemotaxis.

Cell Line↗

[A study on the integration of fetal behavior and the development of association between parameters evaluated].

To evaluate the development of the fetal behavioral state with reference to the association of the fetal parameters we selected, we simultaneously monitored fetal heart rate (FHR), fetal movement (FM), fetal eye movement (FEM) and fetal breathing movement (FBM). These various parameters were monitored with 2 ultrasonographic real time scanners and a doppler device to monitor fetal movement. We assessed the convergence and integration of these four parameters to evaluate the association rate (AR). FHR with a variation in excess of 3 min. was interpreted as the active phase (A), and reduced variation in excess of 3 min. as the inactive phase (I). When FM and FEM were observed in the 1 min. window of A, we labeled this A3, and when FBM was present in more than 10% of the 1 min. window, we labeled it A4. A3/A = AR-A3% and A4/A = AR-A4% was calculated. A similar calculation was done for I, without FM and FEM in the 1 min. window of I (I3) and when FBM was present less than 10% of 1 min. (I4), allow derivation AR-I3% and AR-I4%. A discrete separation of synchrony in A and asynchrony in I can be seen to develop as the fetus matures, and we feel that this may be a valuable tool in the evaluation of fetal central nervous system development in utero.

Central Nervous System↗

[A case of bronchiolitis obliterans organizing pneumonia associated with ulcerative colitis].

A 53-year-old male was admitted to our hospital with fever and chest pain. A chest X-ray film showed infiltrative shadows in the right upper and middle lung field. In spite of administration of antibiotics, the chest X-ray film revealed gradually increasing infiltrates and a new shadow appeared in the left upper lung field. The open lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP). There was marked roentgenographic improvement in response to steroid therapy. Very few cases of BOOP associated with ulcerative colitis have been reported.

Bronchiolitis Obliterans↗

Effects of alkyl substitutions of xanthine skeleton on bronchodilation.

Structure-activity relationships in a series of 1,3,7-trialkyl-xanthine were studied with guinea pigs. Relaxant actions in the tracheal muscle were increased with alkyl chain length at the 1- and 3-positions of the xanthine skeleton, but decreased by alkylation at the 7-position. Positive chronotropic actions in the right atrium were potentiated with 3-alkyl chain length but tended to decrease with 1-alkylation and diminish by 7-substitution. Consequently, while the 1- and 3-substitutions were equally important for the tracheal smooth muscle relaxation, the substitution at the 1-position was more important than the 3-substitution for bronchoselectivity. The 7-alkylation may be significant to cancel heart stimulation. There were good correlations between the smooth muscle relaxant action and the cyclic AMP-PDE inhibitory activity in 3-substituents and the affinity for adenosine (A1) receptors in 1-, 3-, and 7-substituents. This suggests that not only the cyclic AMP-PDE inhibitory activity but also the adenosine antagonistic activity is important in the bronchodilatory effects of alkylxanthines. Among these xanthine derivatives, 1-butyl-3-propylxanthine and its 7-methylated derivative showed high bronchoselectivity in the in vitro and in vivo experiments compared to theophylline and enprofylline and may be new candidates for bronchodilator.

3',5'-Cyclic-AMP Phosphodiesterases↗

Reversal of vinblastine resistance by a new staurosporine derivative, NA-382, in P388/ADR cells.

Activities of a newly synthesized compound, N-ethoxycarbonyl-7-oxo-staurosporine (NA-382), on cyclic AMP-dependent protein kinase (A-kinase), Ca2+/phospholipid dependent protein kinase (C-kinase), and drug resistance were investigated and compared with those of staurosporine. Protein kinase-inhibitory activity of NA-382 was lower but more selective to C-kinase than that of staurosporine. NA-382 was less toxic to P388 cells and at a non-cytotoxic concentration completely reversed the vinblastine (VBL) resistance of Adriamycin-resistant P388 (P388/ADR) cells without influence on the effect of VBL on the parental P388/S cells. However, the cytotoxicity of staurosporine was too high to give the combination effect with VBL. NA-382 dose-dependently increased VBL-accumulation and inhibited VBL-efflux in P388/ADR with higher potency than staurosporine. Both compounds inhibited the photolabeling of [3H]azidopine on 140-kDa P-glycoprotein in the plasma membrane from the resistant cells. These results suggest that a staurosporine analog, NA-382, reverses multidrug resistance by inhibiting the drug-efflux system or P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Relaxant effect of pituitary adenylate cyclase-activating polypeptide on guinea-pig tracheal smooth muscle.

We investigated the relaxant effect of the pituitary adenylate cyclase-activating polypeptide with 27 residues (PACAP27) and with 38 residues (PACAP38) on guinea-pig tracheal smooth muscle. Both forms of PACAP showed dose-dependent relaxant effects. The EC50 of PACAP27 was 8.7 +/- 1.9 x 10(-8) M and that of PACAP38 was 6.8 +/- 1.0 x 10(-8) M. Both increased cyclic AMP levels dose dependently and the elevation of cyclic AMP preceded the relaxation of tracheal smooth muscle. There was a marked difference in the duration of action of the two peptides. PACAP38 showed a longer-lasting relaxation compared to PACAP27. Furthermore PACAP38 maintained significantly higher levels of cyclic AMP, with cyclic AMP levels at 60 min after a 5-min exposure to PACAPs (10(-6) M) being 14.0 +/- 1.4 pM/mg protein for PACAP27 and 35.9 +/- 2.4 pM/mg protein for PACAP38. These results suggest that PACAP27 and PACAP38 may be novel potent relaxants in tracheal smooth muscle and their relaxant effect might be mediated by cyclic AMP. However PACAP38 had a longer-lasting action on relaxation of tracheal smooth muscle and production of tissue cyclic AMP than PACAP27.

Animals↗

Direct activation of phospholipase A2 by GTP-binding protein in human peripheral polymorphonuclear leukocytes.

In human peripheral polymorphonuclear leukocyte (PMN), 10% of PLA2 activity was found in the particulate fraction. In the particulate fraction, the activity of phospholipase A2 was enhanced 270% by 100 microM guanosine 5'-[gamma-thio]triphosphate, a hydrolysis-resistant analog of GTP. In the soluble fraction, such enhancement was not observed. Guanosine 5'-[beta-thio]diphosphate (2 mM), which irreversibly inactivates GTP-binding protein, blocked the enhancement in the particulate fraction. Membrane-binding phospholipase A2 activity of PMN would thus appear to be regulated directly by GTP-binding protein.

Enzyme Activation↗