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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 253 records · Page 14Linked to original sources
PubMed1998

Elevated serum CA19-9 level and regional lymphadenopathy in a young man with allergic bronchopulmonary aspergillosis.

A 21-year-old man with bronchial asthma who suffered from productive cough; his chest X-rays and computed tomographic (CT) scans revealed central atelectasis and pulmonary infiltrates with paratracheal and hilar lymphadenopathy. The serum CA19-9 level was elevated. He was suspected to have malignant neoplasms on admission, but he was diagnosed with allergic bronchopulmonary aspergillosis (ABPA) by Rosenberg's criteria. After steroid therapy, his symptoms and radiographic findings improved and the serum CA19-9 level decreased. ABPA should be considered in the differential diagnosis of asthmatic patients with or without lymphadenopathy and an elevated serum CA19-9 level.

Adult↗
PubMed1998

Acute pulmonary edema caused by accidental aspiration of sweetened water in two cases of diabetes mellitus.

We treated two cases of diabetes mellitus who developed acute pulmonary edema following accidental aspiration of sweetened water for emergency treatment, when they had fallen into hypoglycemic coma following an overdose of injectable insulin. Although they showed hypoxemia and radiological examinations revealed pulmonary edema, they improved by giving only oxygen and antibiotics in a few days. The osmotic pressure of the sweetened water in each case was approximately 2,600 mOsm and 1,900 mOsm. We suppose that the pathogenesis of the pulmonary edema was due to the sweetened water causing water within the pulmonary vessels to permeate into the alveoli.

Acute Disease↗
PubMed1998

Stability of metallothionein isoforms by capillary zone electrophoresis.

Stability of isoforms on storage of metallothionein (MT) was investigated by capillary zone electrophoresis (CZE) at neutral pH. The mouse liver was removed 1 day after injection of zinc, and homogenized in 0.25 M sucrose with 100 mM TRIS-HCl buffer, pH 7.4. The specimens for MT analysis were obtained by two partial purification methods, i.e., heat treatment (HT) and ethanol/chloroform precipitation (ECP) methods. The specimens were stored at either 4 degrees C or -80 degrees C for 1 and 3 days, and peak areas of MT-1 and MT-2 isoforms obtained by CZE were compared. When specimens were obtained by HT method, both MT isoforms were stable at -80 degrees C within 3 days. However, the peak area of MT-1 stored at 4 degrees C was gradually decreased to one third on the 3rd day. The MT-2 peak did not decrease the next day, but decreased to 57% on the 3rd day. In contrast, peak areas of both MT isoforms decreased remarkably the 1st day, when specimens obtained from ECP method were stored at 4 degrees C and -80 degrees C. From these results, we conclude that stability of MT isoforms is different depending on the purification methods, and MT isoforms are not stable after partial purification, especially by ECP method, even if stored at -80 degrees C.

Animals↗
PubMed1998

[A fatal case of aggressive-phase multiple myeloma with ileus and invasion into extramedullary organs].

A 62-year-old woman with IgA-lambda type monoclonal gammopathy had been followed up since January 1988. In March 1991, multiple myeloma (IgA-lambda) was diagnosed on the basis of bone marrow biopsy findings and increased serum IgA levels. She was treated intermittently with melphalan and prednisolone over a perioa of about 6 years, but was eventually admitted due to renal dysfunction, hypercalcemia, increased serum IgA and the formation of subcutaneous masses. During chemotherapy she underwent emergency surgery for obturative ileus. Histological examination of the resected tissues revealed invasion of myeloma cells into the small intestine and peritoneum. Despite continued chemotherapy, the patient's soft tissue masses enlarged, and new lesions appeared in other organs. In the terminal stage, lower serum IgA levels were observed despite an increase in Bence-Jones protein levels in urine. The patient died five months after admission. An autopsy found infiltration by atypical myeloma cells in multiple organs. An immunohistochemical examination revealed and increase in lambda-light chain positive cells relative to the number of alpha-heavy chain positive cells. The terminal course was considered to be representative of aggressive phase multiple myeloma. The case was rare in that the patient's ileus was caused by invasion of myeloma cells into the small intestine.

Disease Progression↗
PubMed1998

[Mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery for severe emphysema].

To investigate the mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery (LVRS) for severe emphysema, we performed six-minute walk tests and pulmonary-function tests, and studied their correlation before and 3-to-5 months after LVRS in 7 patients with severe emphysema who underwent bilateral lung reduction via median sternotomy. Results of the tests showed a 59% increase in the 1-second forced expiratory volume (FEV1), a 25% reduction in the functional residual capacity (FRC), a 49% increase in the maximum voluntary ventilation (MVV), and a 20% increase in the distance walked in 6 minutes (6 MD). The degree of improvement in 6 MD correlated significantly with the degree of improvement in FEV1 (r = 0.97, p < 0.01), in FRC (r = 0.86, p < 0.05), and in MVV (r = 0.87, p < 0.05), and did not correlate with the degree of improvement in pulmonary gas exchange. These results support the hypothesis that an increase in lung elastic recoil after targeted emphysematous resection reduces airflow limitation, and thus leads to a short-term improvement in exercise tolerance after LVRS.

Aged↗
PubMed1998

[A case of paragonimiasis westermani].

A 45-year-old man, who had eaten fried fresh water crabs (Geothelphusa dehaani), was admitted to our hospital because of productive cough and bloodysputum. Blood chemistry showed increased levels of white blood cells and C-reactive protein, but peripheral blood eosinophil counts and serum IgE values were not elevated. Chest roentgenogram and chest computed tomographic scan revealed infiltration of the right middle and left upper lung fields. He was diagnosed as having pneumonia, but his symptoms and radiological examination findings did not improve with antibiotics. The diagnosis of paragonimiasis was confirmed by immunoserological examination and detection of ova in sputum, stool and bronchoalveolar lavage fluid samples. Transbronchial lung biopsy showed infiltration and degranulation of eosinophils. The patient was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg. After uneventful completion of treatment all clinical symptoms and radiological abnormalities disappeared. This is the first case in which ova of paragonimiasis westermani were identified in Nagano prefecture.

Adult↗
PubMed1998

[A case of relapsed thymic carcinoma that responded remarkably to chemotherapy with CPT-11].

A chemotherapeutic protocol for advanced thymic carcinoma has not been established as yet. We described a case of advanced and relapsed thymic carcinoma that responded remarkably to subsequent chemotherapy with CPT-11. A 61-year-old man was admitted to our hospital because of facial edema and general fatigue. Chest X-ray and CT scan showed anterior mediastinal tumor which involved large vessels and pericardium. CT guided needle biopsy yielded a diagnosis of squamous cell type of thymic carcinoma. The patient was initially treated with ADOC (ADM, CDDP, VCR, CPA) chemotherapy and had successfully controlled for six months. However, the mediastinal tumor recurred and radiotherapy and nedaplatin plus ETP therapy were not effective. Then, CPT-11 chemotherapy (80 mg/m2, 2 weeks) was performed. The patient showed a partial response after two courses of CPT-11 chemotherapy. This case suggests that CPT-11 is a useful chemotherapeutic agent for advanced thymic carcinoma.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Pharmacokinetic characteristics of the novel anticancer agent CPT-11 and its active metabolite in plasma and lung lymph fluid following intravenous administration to sheep.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11, 100286-90-6) is one of the most promising novel anticancer agents, especially for lung cancer. 7-Ethyl-10-hydroxycamptothecin (SN-38), an active metabolic of CPT-11, has much stronger cytotoxicity than CPT-11. The present study was designed to evaluate the distribution and behavior of CPT-11 and SN-38 in lung lymph circulation following intravenous infusion. Awake sheep with chronically instrumented lung lymph fistulas were prepared. The concentrations of CPT-11 and SN-38 in plasma and lung lymph fluid were measured after intravenous infusion of 100 mg/body of CPT-11 for 90 min. SN-38 constantly showed higher lymph to plasma concentration ratios than those of CPT-11, and the % area under the curve (AUC) ratio of SN-38/CPT-11 in lymph fluid was significantly higher than that in plasma. These data indicated that SN-38 distributed in lung tissue moved more easily into lung lymph fluid than CPT-11, and might be more rapidly metabolized in lung tissue than plasma. CPT-11 may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis.

Animals↗
PubMed1997

Positively charged liposome functions as an efficient immunoadjuvant in inducing immune responses to soluble proteins.

To design an optimum liposome immunoadjuvant for soluble protein antigens, we investigated the relationship between liposomal surface charge and adjuvant action. Positively charged multilamellar vesicles (MLV) were taken up efficiently by macrophages, while negatively charged and neutral MLVs were hardly picked up. Consistent with this, positively charged MLVs containing soluble chicken egg albumin (OVA) functioned as a more potent inducer of antigen-specific cytotoxic T lymphocyte (CTL) responses and antibody production than negatively charged and neutral MLVs containing the same concentrations of antigens. These results indicate that the positive charge on the surface of liposomes represents an important factor for enhancing their immunoadjuvancy in the induction of antigen-specific immune responses.

Adjuvants, Immunologic↗
PubMed1997

Eosinophil cationic protein levels in induced sputum correlate with the severity of bronchial asthma.

Activated eosinophils play an important role in the pathogenesis of bronchial asthma. In this study, we analyzed the inflammatory leukocyte population and the concentrations of eosinophil cationic protein (ECP) and albumin in induced sputum from patients with mild to severe asthma (n=36), and assessed the findings in relation to the severity of their asthma. Both the eosinophil numbers and the concentrations of ECP in the induced sputum were significantly increased in the patients with asthma compared with those in healthy subjects (n=9). There were significant positive correlations between the ECP levels and both the eosinophil counts (r=0.45) and the albumin concentrations (r=0.53). When the asthmatics were classified as having mild (n=12), moderate (n=14), or severe (n=10) asthma as evaluated by their symptoms and peak expiratory flow rate (PEFR), the ECP levels showed significant increases in accordance with the severity of asthma. The eosinophil counts in the patients with severe asthma were significantly higher than those in the patients with mild and moderate asthma; there was no significant difference between those with mild and moderate asthma. The eosinophil counts and ECP levels were also significantly positively correlated with the mean weekly total symptom scores (r=0.52 and r=0.48, respectively) and negatively with the mean percent PEFR on waking (r=-0.50 and r=-0.65, respectively) recorded for 2 weeks prior to the sputum collection. These findings suggest that the eosinophil activation in the airway is closely linked to the symptoms and airflow obstruction of asthma, and that the ECP concentration in induced sputum could serve as useful marker for evaluating the severity of asthma and monitoring airway inflammation to achieve the optimal control of asthma.

Adolescent↗
PubMed1997

Separation of components of human globulins by capillary zone electrophoresis using a linear polyacrylamide-coated capillary.

Eleven commercially available protein preparation from human serum were subjected to capillary zone electrophoresis (CZE) using a linear polyacrylamide-coated capillary at pH 7.4. Transferrin, complement C3 and C-reactive protein were each separated into one major peak and several minor peaks. alpha 1-Antitrypsin was separated into two major peaks and three minor peaks. alpha 2-HS-glycoprotein showed four major peaks with a leading shoulder. Haptoglobin, alpha 2-macroglobulin, alpha 1-acid-glycoprotein and prealbumin were detected as relatively wide peaks. Ceruloplasmin showed one major peak with notches, and two minor and several notched peaks. Only low density lipoprotein showed no peaks. A mixture of five of the protein preparations was separated into individual components, as well as individual isoforms. When the same mixture was analyzed by CZE using an uncoated capillary, a much poorer resolution was obtained. Application of this CZE system to albumin-depleted serum demonstrated that it is very useful for analyzing globulin components in serum.

Acrylic Resins↗
PubMed1997

Selective inhibition of platelet-derived growth factor (PDGF) receptor autophosphorylation and PDGF-mediated cellular events by a quinoline derivative.

This report describes the biological effects of our original compound, Ki6783 ((3,4-dimethoxy)-4-phenoxy-6,7-dimethoxyquinoline), a potent and selective inhibitor of platelet-derived growth factor (PDGF) receptor autophosphorylation. This compound strongly inhibited autophosphorylation of the PDGF beta-receptor in cultured rat glomerular mesangial cells (MC) bearing this receptor (IC50 0.1 microM), although it did not inhibit autophosphorylation of other growth factor receptors even at 100 microM. In a cell-free kinase experiment, it showed selective inhibition of PDGF beta-receptor tyrosine kinase. A kinetic study of the compound to this tyrosine kinase revealed a competitive mode of action to ATP. [3H]Thymidine incorporation and cell proliferation of MC were inhibited by Ki6783 in a dose-dependent manner after Ki6783 and PDGF-BB were added to the culture medium. Furthermore, this compound normalized the fibrotic cell shape of v-sis-transformed NIH3T3 cells, which grow in an autocrine manner via the PDGF receptor. These effects could be explained by the inhibition of intracellular signal transduction triggered by PDGF receptor autophosphorylation, in which activation of mitogen-activated protein kinase occurs. These results suggest that Ki6783 is one of the more potent and selective inhibitors of PDGF receptor autophosphorylation and that it may be useful in ameliorating cell abnormalities due to excess action of PDGF and its receptor systems in several diseases.

3T3 Cells↗
PubMed1997

Candesartan (CV-11974) dissociates slowly from the angiotensin AT1 receptor.

The mechanisms of the insurmountable antagonism of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]1H-benzimid azole -7-carboxylic acid, candesartan (CV-11974), an angiotensin AT1 receptor antagonist, on angiotensin II-induced rabbit aortic contraction were examined in contraction and binding studies. Preincubation of the rabbit aorta with CV-11974 (0.1 nM) for 30 min reduced the maximal contractile response to angiostensin II by approximately 50%. This insurmountable antagonism of CV-11974 was reversed in the presence of losartan (1 microM), a surmountable angiotensin AT1 receptor antagonist. The inhibitory effect of CV-11974 on angiotensin II-induced contraction persisted longer after washing than did that of losartan but was irreversible. Scatchard analysis of [3H]CV-11974 binding in bovine adrenal cortical membranes indicated the existence of a single class of binding sites (Kd = 7.4 nM). Competition binding studies using angiotensin II receptor agonists and antagonists have demonstrated that [3H[CV-11974 binding sites may be identical to angiotensin AT1 receptors. The dissociation rate of [3H]CV-11974 binding (t1/2 = 66 min) was 5 times slower than that of [125I]angiotensin II binding (t1/2 = 12 min). These results suggest that the insurmountable antagonism by CV-11974 is due to its slow dissociation from angiotensin AT1 receptors.

Adrenal Cortex↗
PubMed1997

Differential effects of beta-endorphin and Met- and Leu-enkephalin on steroid hormone-induced lordosis in ovariectomized female rats.

The effect of intrathirdventricular (I.T.V.) injections of beta-endorphin, anti-beta-endorphin antiserum, Met-enkephalin, Leu-enkephalin, and naloxone on the initial activation and final development of steroid hormone-mediated induction of female sexual receptivity was studied in ovariectomized female rats. The lordosis response to male mounts in ovariectomized rats after subcutaneous (S.C.) estradiol benzoate (EB) and progesterone (Prog) priming was facilitated by beta-endorphin, and Met-enkephalin (10 microg x 5 microl(-1)), but inhibited by Leu-enkephalin, when the peptides were injected into the third ventricle at the time of S.C. EB priming. A lower dose Met-enkephalin had no effects. Lordosis behavior in steroid hormone-primed rats was significantly facilitated when I.T.V. injections of Met-enkephalin were given 1 h prior to behavioral testing (47 h after EB priming). At 1 h prior to behavioral testing (47 h after EB priming), I.T.V. injection of beta-endorphin significantly inhibited lordosis behavior, especially at the higher dose of beta-endorphin (10 microg x 5 microl(-1)). Under those conditions, Leu-enkephalin had no effect. Lordosis behavior of ovariectomized female rats receiving S.C. steroid hormones and I.T.V. injection of anti-beta-endorphin antiserum was significantly inhibited when anti-beta-endorphin antiserum was injected at the time of EB priming. However, lordosis was significantly facilitated when anti-beta-endorphin antiserum was injected 1 h prior to the behavior testing (47 h after EB priming). In contrast, I.T.V. injection of the opioid antagonist naloxone given either at the time of EB priming or 1 h prior to behavioral testing (47 h after EB priming) decreased lordosis behavior. The present results suggest that 1) beta-endorphin, Met-enkephalin, and Leu-enkephalin have differential effects in the control of lordosis behavior; 2) the opioidergic systems may modulate initial-stage and final-stage estrogen-induced lordosis behavior; and 3) the opioidergic systems could be divided into the endorphinergic modulation-type and enkephalinergic modulation-type, based on their effects on lordosis behavior.

Animals↗
PubMed1997

Unusual feature of the T-cell receptor genes in T-lineage acute lymphoblastic leukemia.

We characterized the T-cell receptor (TCR) gene rearrangements and sequences in 15 T-lineage acute lymphoblastic leukemia (T-ALL) and seven adult T-cell leukemia (ATL) samples. Southern blot analysis showed that neither of the two TCR delta alleles was deleted in two T-ALL samples, suggesting that the TCR alpha loci have a germ line configuration. The TCR alpha and beta sequences were cloned and sequenced by reverse transcriptase-inverse polymerase chain reaction. Two T-ALL samples had a long complementarity determining region (CDR), three of the alpha chain and the other two T-ALL samples had long CDR3 of the beta chain, compared with normal peripheral blood lymphocytes (PBL). Thus, a total of six T-ALL samples had unusual TCR gene structure, which was unrelated to the immunophenotype. On the other hand, CDR3 length in ATL samples was similar to normal PBL. These data suggest that T-ALL is derived from an immature T-cell repertoire which undergoes TCR gene rearrangement or has not been negatively selected.

Adolescent↗
PubMed1997

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor, BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth.

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol. 2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats. New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC50 was 1.0 microM in SD rats, 2.1 microM in NZ white rabbits, and 0.3 microM in WHHL rabbits. With human SMC, the value was 0.02 microM in the presence of 10% FCS and 0.2 microM with a mixture of growth factors. 3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg-1 day-1. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P < 0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P < 0.05). By anti-alpha smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P < 0.01). 4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

Animals↗
PubMed1997

Calcium and silicon from bioactive glass concerned with formation of nodules in periodontal-ligament fibroblasts in vitro.

Previously, the authors reported that bioactive glass promoted formation of nodules in cultured periodontal-ligament fibroblasts and high concentrations of calcium and silicon were detected in the culture medium. Herein, the effects of bioactive glass, calcium alone and calcium and silicon for formation of nodules on the periodontal-ligament fibroblasts are examined. The cells were cultured with bioactive glass, without bioactive glass, calcium and silicon, with calcium alone and with calcium and silicon. The cell growth, alkaline-phosphatase activity, amount of pro-collagen type I and the number of nodules were measured periodically until the 21st day. The cell growth rate with calcium and silicon was the highest, however the rate with bioactive glass and calcium alone were similar to that without them. The alkaline-phosphatase activity and the amount of pro-collagen showed peaks at the 11th day. At the peak, the alkaline-phosphatase activity with bioactive glass or calcium and silicon, and the pro-collagen with bioactive glass was higher than without them. The number of nodules with bioactive glass, calcium alone or calcium and silicon was greater than without them. These findings suggested that the combination of calcium and silicon released from bioactive glass was concerned with the formation of nodules on the periodontal-ligament cells.

Alkaline Phosphatase↗