Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 181 records · Page 10Linked to original sources

PubMed1999

A case of amnestic syndrome caused by a subcortical haematoma in the right occipital lobe.

A case of an amnestic syndrome caused by a subcortical haematoma in the right occipital lobe is reported. A 62-year-old right-handed man presented with a sudden onset of headache to the hospital. On admission, he had a left homonymous hemianopsia, disorientation and recent memory disturbance, but had normal remote memory and digit span. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a subcortical haematoma in the right occipital lobe. These findings suggest that the patient's amnesia was caused by a lesion of the retrosplenial region in the non-dominant hemisphere.

Amnesia↗

PubMed1999

Arteriolar and venular vasodilating properties of benidipine hydrochloride, a 1,4-dihydropyridine Ca2+ antagonist with long-lasting action, assessed in rat mesenteric microcirculation.

To obtain direct and visible evidence of the arteriolar vasodilating action in vivo of benidipine hydrochloride, a long-lasting and light-resistant Ca2+ antagonist of the 1,4-dihydropyridine type, we continuously recorded changes in the diameter of mesenteric arterioles (10-40 microm) and venules (20-40 microm) in anesthetized agent-injected Wistar rats by means of digital image processing combined with videomicroscopy. Benidipine injected intravenously brought about a depressor response, and this response persisted much longer than that induced by nifedipine. Benidipine produced a dose-dependent arteriolar vasodilation and a decrease in the blood-flow velocity. It also relaxed the venules during the depressor response, which relaxation was more prominent 1-2 h after the administration. In pithed rats, both pressor response and arteriolar constriction induced by norepinephrine were prevented by benidipine. Benidipine also inhibited adenosine diphosphate (ADP)-induced interruption of arteriolar blood flow. These results suggest that benidipine produced vasodilation in vivo at both the arteriolar and venular levels. The ability of benidipine to prevent microcirculatory disturbance and to produce arteriolar and venular vasodilation seem to account for its long-lasting Ca2+-antagonistic antihypertensive action.

Adenosine Diphosphate↗

PubMed1999

Hydroxyl radical formation following methamphetamine administration to rats.

Administration of neurotoxic doses of methamphetamine (8 mg/kg, intraperitoneally x 4 times, at 2 hr intervals) caused a significant decrease in dopamine and 3,4-dihydroxyphenylacetic acid and an increase in 3-methoxytyramine levels in the striatum along with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in the striatum and hippocampus. In addition, the methamphetamine treatment caused an increase in rat rectal temperature. Intraventricular injection of salicylate 105 min. after the last injection of methamphetamine produced an increase in 2,3- and 2,5-dihydroxybenzoic acid in the striatum and hippocampus. Moreover, the ratio of 2,3-dihydroxybenzoic acid to salicylate was significantly increased in the striatum, but not in the hippocampus. These results indicate that the hydroxyl radical may play an important role in methamphetamine-induced neurotoxicity in rat striatum and that its formation may be the result of methamphetamine-induced release of dopamine.

Animals↗

PubMed1999

Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay.

The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant. The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.

Age Distribution↗

PubMed1999

Bleomycin stimulates lung epithelial cells to release neutrophil and monocyte chemotactic activities.

Although bleomycin, an antineoplastic drug, is used in the treatment of a variety of tumors, the mechanisms of bleomycin-induced lung injury and fibrosis are not fully elucidated. We postulated that bleomycin might stimulate A549 cells, a type II pneumocyte cell line, to release neutrophil and monocyte chemotactic activities (NCA and MCA, respectively). To test this hypothesis, A549 cell supernatant fluids were harvested and evaluated for NCA and MCA. A549 cell supernatant fluids showed NCA and MCA in response to bleomycin in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis revealed that both NCA and MCA were predominantly chemotactic. Partial characterization of the released NCA and MCA showed that the activities were partially heat labile, trypsin digested, and predominantly ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of chemotactic activities significantly. Molecular-sieve column chromatography revealed that the released activities were heterogeneous. However, low-molecular-weight activity was prominent. Leukotriene B4-receptor antagonist, anti-interleukin-8, anti-granulocyte colony-stimulating factor, and anti-monocyte chemoattractant protein-1 antibodies attenuated the chemotactic activities. Immunoreactive leukotriene B4 receptor, interleukin-8, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1 significantly increased in supernatant fluids in response to bleomycin. These data demonstrate that bleomycin stimulates type II epithelial cells to release chemotactic activities and plays a role in inflammatory cell recruitment into the lung.

Antimetabolites↗

PubMed1999

Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities.

Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) B(4)-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an LTB(4)-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung.

Cells, Cultured↗

PubMed1999

Influence of elastic properties of tendon structures on jump performance in humans.

The purpose of this study was to quantify the elastic properties of tendon structures in vivo and to investigate the influence of the tendon properties on jump performance with and without countermovement. Elongation of the tendon and aponeurosis of vastus lateralis muscle (dL) was directly measured by ultrasonography while subjects (n = 31) performed ramp isometric knee extension up to the voluntary maximum (MVC). The relationship between muscle force and dL was fitted to a linear regression above 50% MVC, the slope of which was defined as stiffness of the tendon structures. Statistical analysis revealed no significant difference between duplicated measurements of stiffness, with an interday reliability of r = 0.88 and a coefficient of variance of 6.1%. Although the stiffness was not significantly related to absolute jump height in either vertical jump, it was inversely correlated with the difference in jump height between the vertical jumps performed with and without countermovement. The results suggested that the stiffness of tendon structures has a favorable effect on stretch-shortening cycle exercise, possibly due to adequate storage and recoil of elastic energy.

Adult↗

PubMed1999

Pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia.

We describe the case of a 53-year-old Philadelphia-chromosome-positive woman with chronic myelogenous leukemia, who developed pulmonary alveolar proteinosis (PAP). The possible mechanism involved in the pathogenesis of PAP are discussed based on the clinical and laboratory data for this patient as well as on experimental and clinical data reported in the literature.

Blood Chemical Analysis↗

PubMed1999

Massive pulmonary hemorrhage due to cytomegalovirus infection in a Japanese patient with alpha-1-antitrypsin-deficient emphysema.

Although alpha(1)-antitrypsin (AAT) deficiency is one of the most common hereditary diseases and a recognized cause of emphysema in Caucasians, variants of this deficiency are extremely rare among Orientals. We present here a Japanese emphysema patient with the AAT deficiency variant originally identified as S(iiyama). After an 8-year follow-up period, the patient suffered from repeated pulmonary Pseudomonas aeruginosa infection for 4 years. He died suddenly of massive pulmonary hemorrhage. The pathologic examination revealed a necrotic hematoma in the right S10 lobe, which exhibited pneumonia due to cytomegalovirus (CMV) infection. Pulmonary hemorrhage due to CMV can occur and be fatal in patients with emphysema and AAT deficiency.

Adult↗

PubMed1999

Markers indicating deterioration of pulmonary Mycobacterium avium-intracellulare infection.

To predict the natural history of pulmonary Mycobacterium avium-intracellulare (MAI) infection with nodular bronchiectasis, we retrospectively evaluated clinical manifestations, laboratory data, and bronchoalveolar lavage fluid (BALF) findings in 57 patients. The patients received follow-up chest computed tomographic scans and testing for sputum bacteriology between intervals of at least 12 mo. They were divided into two groups after observation for 28 +/- 13 mo: deteriorated (n = 34) and not-deteriorated (n = 23). There were no patients with spontaneous improvement. At the start of observation, the mean age was greater in the deteriorated group (69 +/- 9 yr) than in the not-deteriorated group (57 +/- 9 yr). The mean body-mass index was lower in the deteriorated group (19.2 +/- 3.1 kg/m(2)) than in the not-deteriorated group (21.5 +/- 1.5 kg/m(2)). C-reactive protein, erythrocyte sedimentation rate, and carbohydrate antigen 19-9 were significantly elevated in the deteriorated group. The BALF findings of the deteriorated group showed that the neutrophil cell counts were significantly increased. Thirty-four of 57 patients with pulmonary MAI infection with nodular bronchiectasis had progressive clinical and/or radiographic disease. The older and thinner patients tended to become worse. Neutrophil-related inflammation associated with a decrease in CD4+ lymphocyte might reflect the progression of pulmonary MAI infection with nodular bronchiectasis.

Aged↗

PubMed1999

Monocyte chemotactic factors released from type II pneumocyte-like cells in response to TNF-alpha and IL-1alpha.

It has been reported that tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 induce the release of monocyte chemotactic factors (MCF), including chemokines, from A549 cells, an alveolar type II cell line. However, the relative contribution of these chemokines to MCF is still uncertain. In the present study, the relative contribution of various chemokines released from A549 cells acting as MCF upon stimulation by TNF-alpha and IL-1alpha, was evaluated. TNF-alpha and IL-1alpha induced the release of MCF in a dose- and time-dependent manner (p<0.001). The release of MCF was inhibited by cycloheximide and lipoxygenase inhibitors. Molecular sieve column chromatography revealed multiple peaks of MCF (near 60 kDa, 25-22 kDa, 15-13 kDa, 8 kDa, and 400 Da). Leukotriene B4 (LTB4) receptor-antagonists inhibited MCF by 50% after 24 h and 30% after 72 h. Monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF)-beta, "regulated on activation, normal T-cells, expressed and secreted" (RANTES), and granulocyte-macrophage colony- stimulating factor (GM-CSF) were released significantly in response to IL-1alpha and TNF-alpha, and antibodies to MCP-1, GM-CSF, and RANTES inhibited MCF activity by 40, 5 and 20% after 24 h, and by 50, 20, and 10% after 72 h, respectively. Each antibody or LTB4 receptor-antagonist inhibited the corresponding column chromatography-separated molecular weight peak of MCF. These data suggest that A549 cells release monocyte chemoattractant protein-1 as the predominant monocyte chemotactic factor rather than granulocyte-macrophage colony-stimulating factor, RANTES, and transforming growth factor-beta, and that leukotriene B4 is constitutively released as a monocyte chemotactic factor.

Cell Line↗

PubMed1999

Serum hepatocyte growth factor in patients with peripheral arterial occlusive disease.

Hepatocyte growth factor (HGF) is a multifunctional protein implicated in tissue regeneration, wound healing, and angiogenesis. We measured serum HGF concentrations in 37 patients with peripheral arterial occlusive disease (PAOD). Among them, 36 patients underwent arteriography. Serum HGF concentrations were also measured in 40 control subjects who remained free of vascular, liver, kidney, or lung disease. Patients with PAOD showed elevated serum HGF concentrations compared with control subjects (0.40+/-0.02 vs. 0.19+/-0.01 ng/mL; P<0.001). Serum HGF concentrations were significantly higher in smokers compared with nonsmokers (0.45+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.003). The serum HGF concentrations in patients with collaterals tended to be higher than those in patients without collaterals (0.43+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.06). Moreover, in patients who underwent bypass surgery or angioplasty, serum HGF concentrations decreased from 0.41+/-0.03 to 0.21+/-0.04 ng/mL after treatment (P<0.001). Serum HGF may be an useful marker for the diagnosis of PAOD. HGF may play an important role in angiogenesis and collateral vessel growth in PAOD.

Adult↗

PubMed1999

Prolongation of the effective duration of cytomedical therapy by re-injecting SK2 hybridoma cells microencapsulated within alginate-poly(L)lysine-alginate membranes into human interleukin-6 transgenic mice.

We previously reported that SK2 hybridoma cells that secreted anti-human interleukin-6 (hIL-6) monoclonal antibodies (SK2 mAb) were microencapsulated within alginate-poly(L)lysine-alginate (APA) membranes (APA-SK2 cells) for immunoisolation, and a single intraperitoneal injection of these APA-SK2 cells remarkably improved IgG1 plasmacytosis in hIL-6 transgenic mice (hIL-6 Tgm). However, the duration of the effectiveness of APA-SK2 cells as a cytomedicine was unfortunately limited. In this study, we attempted to re-inject APA-SK2 cells into hIL-6 Tgm for the purpose of prolonging the cytomedical therapy. In hIL-6 Tgm re-injected with APA-SK2 cells, the plasma IgG1 level did not show any increase in 37 week old mice, and their survival time was at least three times longer than those of untreated hIL-6 Tgm. These results suggest that re-injected APA-SK2 cells survived and secreted SK2 mAb in the allogeneic mice. Thus, the limited duration of the cytomedical effects of APA-SK2 cells was probably caused by the disappearance of the inner space of microcapsules for cell proliferation, not by the rejection of the host's immune system. Therefore, if we can regulate the proliferation of the cells microencapsulated within a semipermeable membrane, we may be able to develop a cytomedicine which will continue its function longer after a single injection.

Alginates↗

PubMed1999

B220 is expressed on apoptotic thymocytes induced by X-irradiation.

CD45 is cell surface glycoprotein and expressed on all haematopoietic cells except mature erythrocytes and platelets. Eight isoforms of CD45 are generated by alternative splicing of exons 4-6. B220 including all three exons is expressed specifically on pan-B cell lineage. Recently, it was reported that B220 was expressed on apoptotic T cells induced by staphylococcal enterotoxin B (SEB). In the present study, we investigated the expression of B220 on murine thymocytes after whole-body X-irradiation. We used the forward light scattering of flow cytometry as a parameter of cell size, and defined two populations; FSChigh (normal cell size) and FSClow (correspond to apoptotic cell in size) fraction. B220+ cells in FSChigh fraction reached a maximum value (35%) at 18 hr after irradiation. In FSClow fraction, 40-60% cells were positive for B220 at any time points. These results suggest that B220 is expressed on thymocytes in the pre-apoptotic stage, because B220 was expressed on not only FSClow cells but also FSChigh cells.

Animals↗

PubMed1999

Flow cytometric analysis of thymocyte subpopulations in mice after whole-body X-irradiation.

To determined the cellular kinetics of thymocyte subpopulations in DBA1 mice after whole-body 6.8 Gy X-irradiation, they were analyzed for the expression of several cell surface antigens using flow cytometry. The results show that i) The majority of thymocytes rapidly depleted by irradiation was CD4+8+ cells. ii) radioresistant CD4+8- and CD4-8+ survived 18-48 hr after X-irradiation were considered to be relatively mature type, since they expressed high levels of CD3 and LECAM-1. iii) CD3-positive cells were detected in CD4-8- cells at 72 hr after irradiation.

Animals↗

PubMed1999

Eosinophilic inflammation in the airway is related to glucocorticoid reversibility in patients with pulmonary emphysema.

STUDY OBJECTIVES: We examined the effects of glucocorticoids on airway inflammation and its association with the reversibility of airflow obstruction in response to oral glucocorticoid administration in patients with COPD. PATIENTS: Twenty-four male patients with smoking-related stable pulmonary emphysema without alpha1-antitrypsin deficiency and nine normal healthy volunteers. MEASUREMENTS: We measured the pulmonary function, the inflammatory cells, and the levels of eosinophil cationic protein (ECP), immunoreactive neutrophil elastase-alpha1-protease inhibitor (NE-alpha1-PI) complex, and interleukin (IL)-8 in sputum induced from patients with pulmonary emphysema in its stable phase before and after treatment with 20 mg oral prednisolone per day for 2 weeks. RESULTS: The eosinophil and neutrophil counts and the concentrations of ECP, NE-alpha1-PI complex, and IL-8 in the sputum were significantly increased at baseline. The eosinophil count at baseline was significantly correlated with the reversibility of airflow obstruction following treatment, and the treatment also significantly reduced the eosinophil numbers and ECP level in the sputum. In contrast, the increased neutrophil number and the concentrations of NE-alpha1-PI complex and IL-8 at baseline did not correlate with the reversibility and were not affected by treatment. CONCLUSIONS: These findings suggest that the eosinophilic inflammation, not neutrophilic inflammation, in the airway is involved in the reversible part of the airflow obstruction in response to glucocorticoids in patients with pulmonary emphysema.

Aged↗

PubMed1999

Proliferation of type II pneumocytes and alteration in their apical surface membrane antigenicity in pulmonary sarcoidosis.

STUDY OBJECTIVE: To evaluate both the proliferation of type II pneumocytes in the alveolitis associated with pulmonary sarcoidosis and any alteration in their surface membrane antigenicity. MATERIALS AND METHODS: We investigated 20 transbronchial lung biopsy (TBLB) specimens from 20 patients with pulmonary sarcoidosis, 7 TBLB specimens from 7 sarcoidosis patients without pulmonary involvement, and 19 normal lung specimens, using colloidal iron stain and immunostaining with anti-Thomsen-Friedenreich (TF) antigen and anti-surfactant protein-A monoclonal antibodies. RESULTS: The density of type II pneumocytes was significantly higher in the pulmonary sarcoidosis specimens ([mean +/- SD] 11.1+/-3.7 per 1 mm alveolar septal length) than in the nonpulmonary sarcoidosis (7.8+/-1.3) or normal lung specimens (7.2+/-0.8). TF antigen was directly expressed on the apical surface of some type II pneumocytes in the pulmonary sarcoidosis specimens, but it was completely masked by sialic acids in the nonpulmonary sarcoidosis specimens and in the normal lung tissues. CONCLUSIONS: In pulmonary sarcoidosis, type II pneumocytes proliferated and the antigenicity of the surface membrane was altered. It is suggested that these type II pneumocytes may be vulnerable to injury by natural anti-TF antibodies that are cytotoxic when present with complement. This damage may decrease alveolar surfactant and cause focal alveolar collapse proceeding to pulmonary fibrosis in some cases of pulmonary sarcoidosis.

Antigens, Surface↗

PubMed1999

Serial scintigraphic assessment of iodine-123 metaiodobenzylguanidine lung uptake in a patient with high-altitude pulmonary edema.

Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) can be considered an indicator of pulmonary endothelial cell function. Serial (123)I-MIBG images of the chest were acquired in a patient with high altitude pulmonary edema (HAPE). The initial evaluation was performed 7 days after admission. The lung to upper mediastinum ratios (LMRs) of (123)I-MIBG uptake were 1.33 (for the right lung) and 1.12 (for the left lung). The second examination of (123)I-MIBG lung uptake, which was performed 2 months later, showed LMRs of 1.39 (right lung) and 1.33 (left lung). We speculated that the decreased lung uptake of (123)I-MIBG at the early recovery stage could reflect an impairment in pulmonary endothelial cell metabolic function in the development of HAPE.

3-Iodobenzylguanidine↗