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1.
Clin Radiol ; 68(12): e669-75, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24025862

ABSTRACT

AIM: To evaluate the volumetric values of intrapulmonary clots (IPCs) using 64-section dual-energy perfusion computed tomography (DEpCT). MATERIALS AND METHODS: A total of 174 patients suspected of having acute pulmonary embolism (PE) underwent DEpCT, and acute PE was diagnosed in 48 of these patients. DEpCT images were three-dimensionally reconstructed with four threshold ranges: 1-120 HU (V120), 1-15 HU (V15), 1-10 HU (V10), and 1-5 HU (V5). Each relative value per V120 was expressed as %V15, %V10 and %V5. These values were compared with the d-dimer, pulmonary arterial (PA) pressure, right ventricular (RV) diameter, RV/left ventricular diameter ratio, PA diameter, and CT angiographic obstruction index (CTOI). RESULTS: In patients with IPCs, PA pressure, d-dimer and volumetric values of DEpCT were significantly higher (p < 0.001). Relative volumetric values at DEpCT had better correlations with the PA pressure, PA diameter, and CTOI than absolute ones, and %V5 especially had good correlations with PA pressure (r = 0.44, p = 0.02), PA diameter (r = 0.40, p = 0.005), and CTOI (r = 0.38, p = 0.009). CONCLUSION: The relative volumetric evaluation of DEpCT images with a lower attenuation threshold range may be helpful for assessing right heart strain, because these values had good correlation with CTOI, pulmonary pressure, and diameter in suggesting right heart load.


Subject(s)
Pulmonary Embolism/diagnostic imaging , Tomography, X-Ray Computed/methods , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Pulmonary Embolism/pathology , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/pathology , Radiography, Dual-Energy Scanned Projection/methods , Severity of Illness Index
2.
Science ; 278(5345): 1940-3, 1997 Dec 12.
Article in English | MEDLINE | ID: mdl-9395395

ABSTRACT

The inositol 1,4,5-trisphosphate (IP3) receptor is a calcium ion channel involved in the release of free Ca2+ from intracellular stores. For analysis of the role of IP3-induced Ca2+ release (IICR) on patterning of the embryonic body, monoclonal antibodies that inhibit IICR were produced. Injection of these blocking antibodies into the ventral part of early Xenopus embryos induced modest dorsal differentiation. A close correlation between IICR blocking potencies and ectopic dorsal axis induction frequency suggests that an active IP3-Ca2+ signal may participate in the modulation of ventral differentiation.


Subject(s)
Body Patterning , Calcium Channels/metabolism , Calcium/metabolism , Embryo, Nonmammalian/metabolism , Inositol 1,4,5-Trisphosphate/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction , Activins , Animals , Antibodies, Blocking , Antibodies, Monoclonal , Calcium Channels/immunology , Cell Differentiation , Embryonic Development , Embryonic Induction , Fibroblast Growth Factor 2/pharmacology , Gastrula/metabolism , Gene Expression Regulation, Developmental , Inhibins/pharmacology , Inositol 1,4,5-Trisphosphate Receptors , Receptors, Cytoplasmic and Nuclear/immunology , Xenopus
3.
Acta Radiol ; 50(1): 34-41, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19052938

ABSTRACT

BACKGROUND: The functional mechanism of lung mosaic computed tomography attenuation (MCA) in pulmonary vascular disease (PVD) and obstructive airway disease (OAD) has not yet been fully clarified. PURPOSE: To clarify the mechanism of MCA in these diseases by assessing the relationship between regional lung function and CT attenuation change at MCA sites with the use of automated deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images and non-breath-hold Technegas SPECT. MATERIAL AND METHODS: Subjects were 42 PVD patients (31 pulmonary thromboembolism, four primary/two secondary pulmonary hypertension, and five Takayasu arteritis), 12 OAD patients (five acute asthma, four obliterative bronchiolitis, and three bronchiectasis), and 12 normal controls, all of whom had MCA on DIBrH CT. The relationship between regional lung function and CT attenuation change at the lung slices with MCA was assessed using DIBrH perfusion SPECT-CT fusion images and non-breath-hold Technegas SPECT. The severity of perfusion defects with or without MCA was quantified by regions-of-interest analysis. RESULTS: On DIBrH CT and perfusion SPECT, in contrast to no noticeable CT attenuation abnormality and fairly uniform perfusion in controls, 60 MCA and 274 perfusion defects in PVD patients, and 18 MCA and 61 defects in OAD patients were identified, with a total of 77 ventilation defects on Technegas SPECT in all patients. SPECT-CT correlation showed that, throughout the 78 MCA sites of all patients, lung perfusion was persistently decreased at low CT attenuation and preserved at intervening high CT attenuation, while lung ventilation was poorly correlated with CT attenuation change. The radioactivity ratios of reduced perfusion and the intervening preserved perfusion at the 78 perfusion defects with MCA were significantly lower than those at the remaining 257 defects without MCA (P<0.0001). CONCLUSION: Although further validation is required, our results indicate that heterogeneous pulmonary arterial perfusion may be a dominant mechanism of MCA in PVD and OAD.


Subject(s)
Lung Diseases/diagnostic imaging , Radiopharmaceuticals , Sodium Pertechnetate Tc 99m , Tomography, Emission-Computed, Single-Photon/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Case-Control Studies , Female , Humans , Image Interpretation, Computer-Assisted , Inhalation , Lung Diseases/physiopathology , Male , Middle Aged , Respiratory Function Tests , Retrospective Studies
4.
Int J Oral Maxillofac Surg ; 37(2): 162-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18023560

ABSTRACT

The purpose of this study was to investigate how the characteristics of a poly-l-lactic acid mini-plate changed with dynamic loading in an environment with hydrolytic degradation. A mandible osteosynthesis model was prepared with specimen poly-l-lactic acid mini-plates to simulate sagittal splitting ramus osteotomy. The model was then subjected to dynamic loading, and changes in specimen shape and surface quality were observed. Specimen bending strength was then measured, and degree of hydrolytic degradation estimated. Neither dynamic loading nor degree of load clearly affected degree of hydrolytic degradation. The specimens maintained their original shape and bending strength for up to 4 weeks with dynamic loading of 40 N or less in an environment with hydrolytic degradation. At 8 weeks, under the same conditions, the specimens showed cracks or fractures, or both, together with a clear decrease in bending strength. The results suggest that dynamic loading causes cracking in a poly-l-lactic acid mini-plate, and that growth of these cracks decreases bending strength over time, leading to fatigue fracture.


Subject(s)
Biocompatible Materials/chemistry , Bone Plates , Lactic Acid/chemistry , Mandible/surgery , Osteotomy/instrumentation , Polymers/chemistry , Buffers , Calorimetry, Differential Scanning , Crystallization , Equipment Design , Equipment Failure , Humans , Hydrolysis , Materials Testing , Models, Anatomic , Molecular Weight , Osteotomy/methods , Pliability , Polyesters , Sodium Chloride/chemistry , Stress, Mechanical , Surface Properties , Time Factors , Transition Temperature , Viscosity
6.
Lymphology ; 40(2): 63-73, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17853616

ABSTRACT

We performed preliminary tests of the feasibility of multi-detector computed tomographic lymphography (MDCT-LG) with interstitial injection of iopamidol for mapping cutaneous lymphatic drainage pathways. MDCT-LG images were obtained following cutaneous injection of a total of 1ml iopamidol bilaterally into hind legs of 10 dogs. The locations of the first draining lymph nodes were marked on the skin under MDCT-LG guidance. Five dogs served for postmortem examination of lymphatic anatomy, and the remaining 5 underwent MDCT-LG after ligation of the afferent lymphatic vessels of the first draining popliteal nodes. Clinically, MDCT-LG was attempted in 6 patients with cutaneous malignant melanoma and compared with Tc-99m-human serum albumin lymphoscintigraphy. MDCT-LG clearly visualized the first draining lymph nodes and their afferent lymphatic vessels draining from the contrast injection sites with detailed underlying anatomy in all dogs. At surgery, all these first draining nodes could be found at predicted locations under MDCT-LG guidance. MDCT-LG showed rerouting of lymphatic vessels after ligation of the afferent lymph vessels of the popliteal nodes in the second 5 dogs. Clinically, MDCT-LG also allowed accurate mapping and biopsy of the first draining nodes from primary tumors at predicted locations, with minimal skin incision. Lymphoscintigraphy failed to identify these nodes due to overlapping radioactivity of clustered nodes or transport of the radiotracer to subsequent distant nodes in 4 patients. Although a more extensive study is warranted for further validation, preoperative interstitial MDCT-LG appears to have the potential feasibility for accurate sentinel lymph node mapping and biopsy in patients with cutaneous melanoma.


Subject(s)
Imaging, Three-Dimensional/methods , Lymphography/methods , Tomography, X-Ray Computed/methods , Aged , Animals , Contrast Media , Dogs , Female , Humans , Iopamidol , Lymph Nodes/pathology , Melanoma/diagnosis , Middle Aged , Sentinel Lymph Node Biopsy/methods , Skin/diagnostic imaging , Skin/pathology , Skin Neoplasms/diagnosis
7.
Cancer Res ; 57(10): 1981-5, 1997 May 15.
Article in English | MEDLINE | ID: mdl-9157994

ABSTRACT

Deletions in the short arm of chromosome 3 have been found in various human cancers, including breast cancer. Recently, the FHIT (fragile histidine triad) gene was identified at 3p14.2 as a candidate tumor suppressor gene. We examined the abnormal transcripts of the FHIT gene in 61 Japanese primary breast cancer specimens and found that 23 (38%) of them exhibited abnormalities, about half of which were categorized into two types of aberrant transcripts. Sequence analysis of these aberrant transcripts revealed the absence of exons 5-7 (type I) and exons 5-8 (type II). Clinicopathological and epidemiological analysis of patients showed that the abnormal FHIT transcripts were not associated with age, tumor-node-metastasis classification, tumor size, estrogen receptor and progesterone receptor status, local metastasis, family history of breast cancer, or lifestyle factors of patients, including cigarette smoking and alcohol consumption. On the other hand, we found that the abnormal transcripts of type I and type II were associated with the incidence of bilateral breast cancer and that decreased frequency of childbirth was also associated with FHIT abnormalities.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Chromosome Fragility , Genes, Tumor Suppressor , Adult , Aged , Breast Neoplasms/epidemiology , Exons , Female , Histidine/genetics , Humans , Japan/epidemiology , Middle Aged , Polymerase Chain Reaction , Transcription, Genetic
8.
J Laryngol Otol ; 130(10): 914-922, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27604559

ABSTRACT

OBJECTIVES: To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy. METHODS: Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted. RESULTS: Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site. CONCLUSION: The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.


Subject(s)
Adipocytes/transplantation , Adipose Tissue/transplantation , Stem Cell Transplantation/methods , Vocal Cord Paralysis/therapy , Adipocytes/cytology , Adipose Tissue/cytology , Animals , Disease Models, Animal , Hypertrophy/etiology , Laryngeal Muscles/pathology , Larynx/pathology , Muscular Atrophy/etiology , Pilot Projects , Swine , Transplantation, Autologous , Treatment Outcome , Vocal Cords/pathology
9.
Cell Death Differ ; 7(5): 439-46, 2000 May.
Article in English | MEDLINE | ID: mdl-10800077

ABSTRACT

Oncogenic and anti-apoptotic Bcl-2 is expressed much less in estrogen receptor alpha (ERalpha) negative breast cancers, which show more malignant phenotypes, than ERalpha-positive, indicating that some other Bcl-2 family member(s) are involved in the apoptotic balance of the cancer cells. We first analyzed mRNA expression of pro-apoptotic Bak and Bax along with that of anti-apoptotic Bcl-2 and Bcl-xL, using breast cancer specimens of 27 patients. Bak mRNA was expressed much less in ERalpha negative breast cancers, along with reduced expression of Bcl-2. Immunostaining of sections of 108 patients confirmed the observation. Next, stable transformants of MCF-7 cells with sense Bak expression vector showed fewer colonies in soft agar compared with the parental cells, while stable introduction of antisense Bak vector enhanced colony formation at lower estradiol concentrations. The reduction of Bak may play important roles in malignant development of breast cancer to acquire estrogen independency, counteracting the reduced Bcl-2.


Subject(s)
Apoptosis/genetics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Genes, bcl-2 , Membrane Proteins/genetics , Neoplasms, Hormone-Dependent/genetics , Neoplasms, Hormone-Dependent/metabolism , Receptors, Estrogen/metabolism , Base Sequence , Breast Neoplasms/pathology , DNA Primers/genetics , Female , Gene Expression , Humans , Immunohistochemistry , Membrane Proteins/metabolism , Multigene Family , Neoplasms, Hormone-Dependent/pathology , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Transformation, Genetic , Tumor Cells, Cultured , bcl-2 Homologous Antagonist-Killer Protein , bcl-2-Associated X Protein , bcl-X Protein
10.
Clin Cancer Res ; 5(6): 1249-61, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10389907

ABSTRACT

BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. To clarify the possible involvement of the BRCA1 protein in mammary carcinogenesis in sporadic and hereditary forms, we have analyzed the BRCA1 protein expression pattern in five breast epithelial cell lines, including a BRCA1-deficient cell line, and 162 breast cancer tissue samples [including 108 sporadic, 35 hereditary (BRCA1 status unknown), and 19 BRCA1-associated cases] from Japanese women. Twelve anti-BRCA1 antibodies were tested by fixation conditions, in which nuclear localization of BRCA1 protein was preserved, and by specificity of the antibodies, which was evaluated in BRCA1-deficient cancer cells. Using monoclonal antibodies applicable to immunohistochemical analysis of paraffin-embedded tissue sections, we found high-level expression of BRCA1 protein in normal mammary epithelium and various degrees of reduced expression in breast cancer cells. Of the 19 BRCA1-associated breast cancer tissues, 15 (79%) showed reduction (8 cases) or complete loss (7 cases) of nuclear expression. Thirty (28%) of 108 sporadic and 6 (17%) of 35 hereditary carcinomas showed reduced BRCA1 protein expression. Reduction of BRCA1 protein expression in sporadic carcinomas was associated with solid-tubular phenotype, with poor tubular differentiation, and with an overexpression of c-erbB-2 protein, which is one of the prognostic factors in breast cancer. Our data suggest that reduced expression of BRCA1 protein may play an important role in mammary carcinogenesis, not only in BRCA1-associated breast carcinomas, but also in sporadic carcinomas, and also suggest that mechanisms other than mutation may be involved in its reduced expression.


Subject(s)
BRCA1 Protein/biosynthesis , Breast Neoplasms/metabolism , Animals , Antibodies, Monoclonal/metabolism , Antibody Specificity , BRCA1 Protein/immunology , BRCA1 Protein/metabolism , Cells, Cultured , Female , Gene Expression , Humans , Immunoblotting , Immunohistochemistry , Japan , Mammary Neoplasms, Experimental/metabolism , Precipitin Tests , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Nude , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Tissue Fixation , Tumor Suppressor Protein p53/metabolism
11.
J Leukoc Biol ; 54(1): 40-6, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8336078

ABSTRACT

We examined leukemic cells, HL-60, an acute promyelocytic leukemia cell line, after differentiation induced by 1,25-dihydroxyvitamin D3 (D3) and retinoic acid (A) for infection of Legionella pneumophila, the etiologic agent of Legionnaires' disease. We investigated the effect of interferon gamma (IFN-gamma) on the differentiated cells and on the intracellular growth of the bacteria. An examination of morphological and antigenic changes in the cells was also included in the study. After 4-day incubation with 10(-6)M D3 or A, the HL-60 cells differentiated into monocyte-like (D3-HL-60) or mature granulocyte-like (A-HL-60) cells, respectively. They were then infected with L. pneumophila. Intracellular multiplication of the bacteria was evident in D3-HL-60 cells but not in HL-60 or A-HL-60 cells. D3-HL-60 cells required a 24-h infection time for the intracellular growth of L. pneumophila. D3-HL-60 cells activated with human recombinant IFN-gamma for 1-24 h (gamma-IFN-D3-HL-60 cells) before infection markedly inhibited L. pneumophila multiplication, the effect of IFN-gamma being dose dependent. Surface marker analysis was carried out in HL-60, D3-HL-60, and gamma-IFN-D3-HL-60 cells. On D3-HL-60 cells, CD11b, CD11c, CD14, and CD35 antigen increased, whereas CD71 and HLA-DR antigen decreased. This finding suggested that HL-60 cells differentiated into monocyte-like cells; the acquisition of the complement receptors, CD11b(CR3) and CD35(CR1), seemed to be important for phagocytosis and for the subsequent intracellular multiplication of L. pneumophila. The gamma-IFN-D3-HL-60 cells showed an increase of CD16, CD36, CD71, and HLA-DR antigen, suggesting that they were in an activated state. Our study indicated, first, that D3 can induce human leukemic cells to differentiate into functional monocyte-macrophage-like cells that can support the intracellular multiplication of L. pneumophila and, second, that these differentiated leukemic cells can be activated by IFN-gamma to markedly inhibit bacterial growth.


Subject(s)
Calcitriol/pharmacology , Interferon-gamma/pharmacology , Legionella pneumophila/growth & development , Leukemia, Promyelocytic, Acute/microbiology , Animals , Antigens, Bacterial/analysis , Antigens, CD/analysis , Antigens, Neoplasm/analysis , Cell Differentiation/drug effects , Guinea Pigs , Humans , Intracellular Fluid/microbiology , Legionella pneumophila/drug effects , Legionella pneumophila/immunology , Legionnaires' Disease/drug therapy , Legionnaires' Disease/pathology , Leukemia, Experimental/microbiology , Leukemia, Experimental/pathology , Leukemia, Promyelocytic, Acute/immunology , Leukemia, Promyelocytic, Acute/pathology , Macrophage Activation , Macrophages/cytology , Macrophages/drug effects , Macrophages/physiology , Monocytes/cytology , Monocytes/drug effects , Monocytes/physiology , Recombinant Proteins , Tretinoin/pharmacology , Tumor Cells, Cultured
12.
Mol Immunol ; 34(12-13): 887-90, 1997.
Article in English | MEDLINE | ID: mdl-9464524

ABSTRACT

The interaction between a single chain Fv (sFv) of the monoclonal antibody 3A21 and its antigen, bovine pancreatic ribonuclease A (RNase A), was studied by site-directed mutagenesis of the hypervariable regions and fluorescence polarization analysis. The affinity constants of wild-type sFv and a mutant sFv D31A (Asp31 of heavy chain was replaced by Ala) for RNase A were found to be 2.7 x 10(7) and 4.7 x 10(6) M(-1) in PBS at pH 7.2 and 37 degrees C, respectively. Whereas the affinity constant of D31A is not affected by NaCl concentration, that of wild-type sFv is almost the same as that of D31A in the presence of more than 1 M NaCl. These results demonstrate that Asp31 of the heavy chain interacts electrostatically with a positively charged amino acid residue of RNase A.


Subject(s)
Antibodies, Monoclonal/metabolism , Immunoglobulin Fragments/metabolism , Immunoglobulin Variable Region/metabolism , Ribonuclease, Pancreatic/metabolism , Animals , Cattle , Chromatography, Affinity , Fluorescence Polarization , Hydrogen-Ion Concentration , Immunoglobulin Fragments/chemistry , Immunoglobulin Variable Region/chemistry , Pancreas/enzymology , Protein Binding/drug effects , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Ribonuclease, Pancreatic/chemistry , Sodium Chloride/pharmacology
13.
Mol Immunol ; 34(10): 731-4, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9430200

ABSTRACT

The interaction between a single-chain Fv (sFv) of the monoclonal antibody 3A21 and its antigen, bovine pancreatic ribonuclease A (RNase A), was studied by site-directed mutagenesis of the hypervariable regions and fluorescence polarization analysis. The affinity constants of wild-type sFv and a mutant sFv D31A (Asp31 of heavy chain was replaced by Ala) for RNase A were found to be 2.7 x 10(7) and 4.7 x 10(6) M-1 in PBS at pH 7.2 and 37 degrees C, respectively. While the affinity constant of D31A is not affected by NaCl concentration, that of wild-type sFv is almost the same as that of D31A in the presence of more than 1 M NaCl. These results demonstrate that Asp31 of the heavy chain interacts electrostatically with a positively charged amino acid residue of RNase A.


Subject(s)
Immunoglobulin Fragments/immunology , Ribonuclease, Pancreatic/immunology , Alanine/genetics , Amino Acid Substitution/genetics , Amino Acid Substitution/immunology , Antibodies, Monoclonal/immunology , Asparagine/genetics , Fluorescence Polarization Immunoassay , Hydrogen-Ion Concentration , Immunoglobulin Fragments/genetics , Mutagenesis, Site-Directed , Protein Binding/immunology , Salts/immunology , Sodium Chloride/pharmacology
14.
Cardiovasc Res ; 21(6): 439-46, 1987 Jun.
Article in English | MEDLINE | ID: mdl-2820576

ABSTRACT

To investigate the effect of inhibition of cerebral Na+, K+-ATPase on cardiovascular regulation ouabain was injected into the lateral ventricle or the posterior hypothalamus in either conscious or urethane anaesthetised, deoxycorticosterone-salt hypertensive (DOCA) and sham operated (sham) rats. Ouabain injected intracerebroventricularly produced dose dependent vasopressor responses and tachycardia in the conscious rat; the magnitude of the pressor response was consistently larger in DOCA than in sham rats. In anaesthetised rats the pressor responses were accompanied by corresponding increases in abdominal sympathetic nerve activity. Thus the magnitude of the pressor responses, tachycardia, and the increases in nerve activity was again significantly greater in DOCA than in sham rats. Intrahypothalamic injections of ouabain produced pressor responses that were accompanied by consistent increases in both heart rate and abdominal sympathetic nerve activity in anaesthetised rats. In contrast to the intracerebroventricular injections the percentage increases from baseline blood pressure were significantly greater in sham than in DOCA rats at 5 min after injection. These results indicate that the centrally induced vasopressor response to ouabain, via the periventricular or bulbospinal system or both, is increased in DOCA-salt hypertensive rats whereas the pressor mechanism via the posterior hypothalamus is suppressed in DOCA rats.


Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Hypertension/physiopathology , Ouabain/pharmacology , Sympathetic Nervous System/drug effects , Action Potentials/drug effects , Animals , Desoxycorticosterone , Hypertension/chemically induced , Hypothalamus/drug effects , Injections, Intraventricular , Rats , Rats, Inbred Strains , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors
15.
FEBS Lett ; 489(2-3): 249-53, 2001 Feb 02.
Article in English | MEDLINE | ID: mdl-11165259

ABSTRACT

CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well as amino acid transport. We show that CD98 cross-linking persistently activates Rap1 GTPase in a LFA-1-dependent manner and induces LFA-1/ICAM-1-mediated cell adhesion in lymphocytes. Specific phosphatidylinositol-3-kinase (PI3K) inhibitors suppressed both LFA-1 activation and Rap1GTP generation, and abrogation of Rap1GTP by retroviral over-expression of a specific Rap1 GTPase activating protein, SPA-1, totally inhibited the LFA-1/ICAM-1-mediated cell adhesion. These results suggest that CD98 cross-linking activates LFA-1 via the PI3K signaling pathway and induces accumulation of Rap1GTP in a LFA-1-dependent manner, which in turn mediates the cytoskeleton-dependent cell adhesion process.


Subject(s)
Antigens, CD/physiology , Carrier Proteins/physiology , Lymphocyte Function-Associated Antigen-1/physiology , Lymphocytes/cytology , rap1 GTP-Binding Proteins/metabolism , Androstadienes/pharmacology , Animals , Antibodies, Monoclonal/pharmacology , Antigens, CD/immunology , Carrier Proteins/immunology , Cell Adhesion/drug effects , Cell Aggregation/drug effects , Cell Line , Cells, Cultured , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Fusion Regulatory Protein-1 , Humans , Intercellular Adhesion Molecule-1/physiology , Lymphocytes/drug effects , Lymphocytes/metabolism , Mice , Phosphoinositide-3 Kinase Inhibitors , Wortmannin
16.
J Interferon Cytokine Res ; 21(9): 695-707, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11576464

ABSTRACT

Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.


Subject(s)
Alkaline Phosphatase/drug effects , Bone Morphogenetic Proteins/pharmacology , Interleukin-11/pharmacology , Neoplasm Proteins , Nerve Tissue Proteins , Osteoblasts/cytology , Osteocalcin/drug effects , Receptors, Cytoplasmic and Nuclear/drug effects , Transcription Factors/drug effects , Transforming Growth Factor beta , Tumor Suppressor Proteins , Animals , Bone Morphogenetic Protein 2 , Carrier Proteins/drug effects , Carrier Proteins/genetics , Cell Differentiation/drug effects , Cell Line/cytology , Collagen Type II/drug effects , Collagen Type II/genetics , Drug Synergism , Fatty Acid-Binding Protein 7 , Fatty Acid-Binding Proteins , Humans , Integrin-Binding Sialoprotein , Mice , MyoD Protein/drug effects , MyoD Protein/genetics , Osteocalcin/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Parathyroid Hormone/drug effects , Receptors, Parathyroid Hormone/genetics , Recombinant Proteins/pharmacology , Sialoglycoproteins/drug effects , Sialoglycoproteins/genetics , Transcription Factors/genetics
17.
J Hypertens ; 5(6): 677-82, 1987 Dec.
Article in English | MEDLINE | ID: mdl-2892883

ABSTRACT

Cardiovascular regulation during alpha 1-adrenergic blocker-induced vasodepression was investigated in urethane-anaesthetized rats. Intravenous (i.v.) injections of bunazosin, an alpha 1-blocker, elicited depressor responses which were accompanied by corresponding decreases in both heart rate and abdominal sympathetic discharge, dose-dependently. Those responses were not affected by the bilateral sino-aortic de-afferentation. Assuming that the site of action is in the central nervous system, bunazosin was injected intracerebroventricularly (i.c.v.). It produced hypotension accompanied by decreases in heart rate and abdominal sympathetic nerve activity. The magnitude of the responses was greater when bunazosin was injected i.c.v. than when injected i.v. Since these results indicated that the central alpha 1-adrenergic receptors mediate vasopressor responses, the effects of i.c.v. injections of an alpha 1-agonist, phenylephrine was explored. It elicited vasopressor responses accompanied by corresponding increases in heart rate and abdominal sympathetic nerve activity. Furthermore, i.c.v. pretreatment with bunazosin abolished the vasopressor responses to i.c.v. injections of phenylephrine. These results indicate that central alpha 1-adrenergic receptors mediate vasopressor responses and that i.v. injections of alpha 1-blockers affect the central alpha 1-receptors, to produce a decrease in sympathetic nerve activity. Consequently, alpha 1-adrenergic blockers decrease blood pressure not only by peripheral vasodilation but also by inhibition of the sympathetic outflow in rats.


Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Quinazolines/pharmacology , Sympathetic Nervous System/drug effects , Animals , Blood Pressure/drug effects , Denervation , Heart Rate/drug effects , Injections, Intravenous , Injections, Intraventricular , Phentolamine/pharmacology , Phenylephrine/pharmacology , Pressoreceptors/physiology , Rats , Rats, Inbred Strains
18.
J Nucl Med ; 34(11): 1980-3, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8229244

ABSTRACT

A case of primary pulmonary malignant lymphoma (PML) was evaluated by 123I-IMP scintigraphy and 201TlCl SPECT. Radiography and CT showed a so-called lobar consolidation on the chest that was difficult to differentiate from other benign conditions. However, 123I-IMP scintigraphy showed a defect corresponding to the lesion both in the early and delayed images, and 201TlCl SPECT showed a higher retention index than that of benign disorders. Both results were highly suggestive of malignancy. These scintigraphies can help differentiate PML from benign lesions and other malignant pulmonary tumors.


Subject(s)
Amphetamines , Lung Neoplasms/diagnostic imaging , Lymphoma/diagnostic imaging , Thallium , Female , Humans , Iofetamine , Lung/diagnostic imaging , Lung/pathology , Lung Neoplasms/pathology , Lymphoma/pathology , Middle Aged , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
19.
J Nucl Med ; 39(3): 543-7, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9529308

ABSTRACT

UNLABELLED: To establish the effect of an aerosolized synthetic surfactant (Exosurf) on pulmonary 99mTc-diethylenetriamine pentaacetic acid (DTPA) aerosol deposition and clearance, radioaerosol studies were performed at varying times and under varying conditions after surfactant inhalation in canine lungs. METHODS: Twenty-three dogs had a baseline 99mTc-DTPA study; 2 days later the study was repeated after inhalation of a 1.5-ml/kg dose of Exosurf aerosolized by an ultrasonic nebulizer. The clearance half-time (T1/2) of 99mTc-DTPA from each lung was measured at different times (from 10 min to 3 hr) after Exosurf inhalation. For comparison, five animals had a 99mTc-DTPA study 10 min after inhalation of the same dose of saline as Exosurf. An additional five animals inhaled a 99mTc-DTPA-Exosurf mixture to investigate the distribution of Exosurf. RESULTS: Technetium-99m-DTPA distributed uniformly without significant changes in penetration indexes before and after inhalation of Exosurf and the 99mTc-DTPA-Exosurf mixture. After Exosurf inhalation, 99mTc-DTPA clearance at 10 min (T1/2; 35.6 +/- 8.7 min; n = 6) and 40 min (29.4 +/- 6.3 min; n = 4) was significantly prolonged compared with the matched baseline values (24.7 +/- 6.4 min, p < 0.0001; and 21.7 +/- 8.9 min, p = 0.01, respectively). However, later clearance times were not prolonged. By contrast, after saline inhalation, 99mTc-DTPA distributed inhomogeneously, and clearance times T1/2) were not altered from the matched baseline values. CONCLUSION: Aerosolized Exosurf distributes homogeneously in the lungs. Exosurf initially retards 99mTc-DTPA aerosol clearance, but 99mTc-DTPA transalveolar clearance returns to baseline rates within 1-2 hr. Technetium-99m-DTPA aerosol clearance measurements can be used to monitor the effect of inhaled Exosurf on pulmonary epithelial integrity.


Subject(s)
Fatty Alcohols/pharmacology , Lung/diagnostic imaging , Phosphorylcholine , Polyethylene Glycols/pharmacology , Pulmonary Surfactants/pharmacology , Radiopharmaceuticals , Technetium Tc 99m Pentetate , Administration, Inhalation , Aerosols , Animals , Dogs , Drug Combinations , Fatty Alcohols/administration & dosage , Fatty Alcohols/pharmacokinetics , Lung/drug effects , Lung/metabolism , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/pharmacokinetics , Pulmonary Surfactants/administration & dosage , Pulmonary Surfactants/pharmacokinetics , Radionuclide Imaging , Time Factors
20.
J Nucl Med ; 35(9): 1520-7, 1994 Sep.
Article in English | MEDLINE | ID: mdl-8071704

ABSTRACT

UNLABELLED: We evaluated the ability of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) to serve as a sensitive marker of lung injury. METHODS: Two experimental rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, we clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of 99mTc-HMPAO in the lungs. RESULTS: Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of 99mTc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of 99mTc-HMPAO activity in the patients who received chemotherapy (0.649 +/- 0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387 +/- 0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. CONCLUSION: These findings suggest that 99mTc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury.


Subject(s)
Antineoplastic Agents/adverse effects , Lung/diagnostic imaging , Organotechnetium Compounds , Oximes , Radiation Injuries/diagnostic imaging , Adult , Aged , Animals , Antineoplastic Agents/therapeutic use , Female , Humans , Lung/drug effects , Lung/radiation effects , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Male , Middle Aged , Oleic Acid , Oleic Acids , Rabbits , Radiation Injuries, Experimental/diagnostic imaging , Radionuclide Imaging , Technetium Tc 99m Exametazime
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