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1.
Int J Obes (Lond) ; 40(11): 1655-1661, 2016 11.
Article in English | MEDLINE | ID: mdl-27430878

ABSTRACT

BACKGROUND/OBJECTIVES: Brown adipose tissue (BAT) is a potential therapeutic target against obesity and diabetes through thermogenesis and substrate disposal with cold exposure. The role of BAT in energy metabolism under thermoneutral conditions, however, remains controversial. We assessed the contribution of BAT to energy expenditure (EE), particularly diet-induced thermogenesis (DIT), and substrate utilization in human adults. METHODS: In this cross-sectional study, BAT activity was evaluated in 21 men using 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) after cold exposure (19 °C). The subjects were divided into BAT-positive (n=13) and BAT-negative (n=8) groups according to the 18F-FDG-PET/CT findings. Twenty-four hour EE, DIT and respiratory quotient were measured using a whole-room indirect calorimeter at 27 °C. RESULTS: Body composition, blood metabolites and 24-h EE did not differ between groups. DIT (%), calculated as DIT divided by total energy intake, however, was significantly higher in the BAT-positive group (BAT-positive: 9.7±2.5%, BAT-negative: 6.5±4.0%, P=0.03). The 24-h respiratory quotient was significantly lower (P=0.03) in the BAT-positive group (0.861±0.027) than in the BAT-negative group (0.889±0.024). CONCLUSION: DIT and fat utilization were higher in BAT-positive subjects compared to BAT-negative subjects, suggesting that BAT has a physiologic role in energy metabolism.


Subject(s)
Adipose Tissue, Brown/metabolism , Asian People , Energy Metabolism/physiology , Thermogenesis/physiology , Adipose Tissue, Brown/diagnostic imaging , Adult , Cold Temperature , Cross-Sectional Studies , Energy Intake/physiology , Fluorodeoxyglucose F18/therapeutic use , Healthy Volunteers , Humans , Japan , Male , Middle Aged , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals/therapeutic use
2.
Diagn Interv Imaging ; 96(5): 487-93, 2015 May.
Article in English | MEDLINE | ID: mdl-25686775

ABSTRACT

GOALS: To compare the quality of low-dose CT images with sinogram affirmed iterative reconstruction (SAFIRE), and full-dose CT with filtered back projection reconstructions (FBP). MATERIALS AND METHODS: Fifty pulmonary CT performed by a dual-source technique (120kVp; 110mAs) with (a) the same energy in both tubes, and (b) the distribution of reference mAs with 40% in tube A (44mAs) and 60% in tube B (66mAs). Each acquisition allowed reconstruction of: (a) full-dose images (with both tubes) with FBP reconstructions (group 1); and (b) low-dose images (from tube A) reconstructed with SAFIRE (group 2). RESULTS: Group 2 images presented: (a) a significant objective reduction in noise measured in the trachea on mediastinal (16.04±5.66 vs 17.66±5.84) (P=0.0284) and pulmonary (29.77±6.79 vs 37.96±9.03) (P<0.0001) images; (b) a similar subjective perception of noise and overall image quality (P=1), which was considered to be excellent in 66% (33/50) of the cases, with no influence on the detection of elementary pulmonary lesions of infiltration (98.4%; 95% CI=[96.9%-99.9%]). CONCLUSION: Despite a 60% reduction in radiation dose, the image quality with iterative reconstruction is objectively better and subjectively similar to full-dose FBP images.


Subject(s)
Image Processing, Computer-Assisted , Pulmonary Artery/diagnostic imaging , Radiation Dosage , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Angiography/methods , Female , Humans , Male , Middle Aged , Young Adult
3.
Diagn Interv Imaging ; 94(6): 609-17, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23601360

ABSTRACT

PURPOSE: To provide quantitative information on emphysema in asymptomatic smokers in correlation with pulmonary function tests (PFT). PATIENTS AND METHODS: The study population included 75 smokers (current smokers: n=39; ex-smokers: n=36) and 25 nonsmokers who underwent volumetric high-resolution CT of the chest with automated quantification of emphysema and PFTs. RESULTS: Current smokers had a higher percentage of emphysema in the right lung (P=0.041) and right upper lobe (P=0.037). The overall percentage of emphysema did not differ according to the Gold stage (P=0.77). Smokers with emphysema had significantly higher mean values of FRC (P=0.012), RV (<0.0001) and TLC (P=0.0157) than smokers without emphysema but no significant differences were found in neither the mean values of TLCO nor in expiratory flows (P>0.05). Correlations were found between the percentage of emphysema and (a) cigarette consumption of current (r=0.34215; P=0.0330) and ex-smokers (r=0.44104; P=0.0071); and (b) alterations of TLC, FRC, RV and DLCO of smokers. CONCLUSION: Quantitative CT allows recognition of regional specificities and subclinical functional alterations in smokers with emphysema.


Subject(s)
Cone-Beam Computed Tomography/methods , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Lung Volume Measurements , Pulmonary Diffusing Capacity/physiology , Pulmonary Emphysema/diagnostic imaging , Smoking/adverse effects , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pulmonary Emphysema/physiopathology , Sensitivity and Specificity , Smoking Cessation , Statistics as Topic
4.
Arq. bras. med. vet. zootec ; 65(2): 359-363, abr. 2013. ilus, tab
Article in English | LILACS | ID: lil-673108

ABSTRACT

The findings of b-mode and especially triplex Doppler ocular ultrasound in the evaluation of 10 Poodle dogs with cataracts, which bring a contribution not yet reported in veterinary medicine, were reported. Ten Poodle dogs of varied ages and presenting cataracts were used. All animals were evaluated for ophthalmic and ultrasound examination. The ultrasound examination allowed the evaluation of the sonographic anatomy of the eye and measurement of the axial thickness of the lens (ATL). Using the Doppler mode, the blood flow of the ophthalmic artery and its vascular indexes, systolic velocity (SV), resistive index (RI) and pulsatility index (PI) were measured. Values found for ATL were 5.89±1.05 for the right eye (OD) and 6.07±1.32 for the left eye (OS). Values found using Doppler evaluation were SV OD: 26.54±7.05 and SV OS: 29.21±11.18; PI OD: 1.89±0.61 and PI OS: 1.7±0.35; RI OD: 0.76±0.1 and RI OS: 0.72±0.09 (OS). It was concluded that triplex Doppler was important for the determination of vascular indexes of the ophthalmic artery, which can be used for monitoring animals with hemodynamic alterations of the eyes and monitoring the therapy of ocular diseases.


Descreveram-se os achados da ultrassonografia ocular convencional e, principalmente, do modo Doppler Triplex na avaliação de 10 cães da raça Poodle com catarata, contribuindo com parâmetros ainda não relatados em medicina veterinária. Foram utilizados 10 cães de diferentes idades e da raça Poodle, apresentando graus variados de catarata. Os animais foram submetidos ao exame oftalmológico e ultrassonográfico. Por meio da ultrassonografia avaliaram-se a anatomia ultrassonográfica dos bulbos oculares e a espessura axial da lente (EAL). Por meio do modo Doppler verificaram-se o tipo de fluxo sanguíneo da artéria oftálmica e seus índices vasculares, a velocidade sistólica (VS), o índice de resistência (RI) e a pulsatividade (PI). Os valores de EAL para olho direito (OD) foi de 5,89±1,05 e para o olho esquerdo (OE) de 6,07±1,32. Por meio do Doppler, observaram-se VS para OD de 26,54±7,05 e VS para OE de 29,21±11,18; PI para OD de 1,89±0,61 e PI para OE de 1,7±0,35; RI para OD de 0,76±0,1 e PI para OE de 0,72±0,09. Concluiu-se que o modo Doppler Triplex mostrou-se importante para determinação das medidas dos índices vasculares da artéria oftálmica, podendo ser utilizada para o acompanhamento de alterações hemodinâmicas nos olhos dos animais acometidos e no acompanhamento da terapia de doenças oculares.


Subject(s)
Animals , Dogs , Cataract/pathology , Eye , Ultrasonography , Dogs , Ophthalmology/methods
5.
J Phys Chem A ; 114(34): 9098-109, 2010 Sep 02.
Article in English | MEDLINE | ID: mdl-20690588

ABSTRACT

The pyrolysis and oxidation of diethyl ether (DEE) has been studied at pressures from 1 to 4 atm and temperatures of 900-1900 K behind reflected shock waves. A variety of spectroscopic diagnostics have been used, including time-resolved infrared absorption at 3.39 mum and time-resolved ultraviolet emission at 431 nm and absorption at 306.7 nm. In addition, a single-pulse shock tube was used to measure reactant, intermediate, and product species profiles by GC samplings at different reaction times varying from 1.2 to 1.8 ms. A detailed chemical kinetic model comprising 751 reactions involving 148 species was assembled and tested against the experiments with generally good agreement. In the early stages of reaction the unimolecular decomposition and hydrogen atom abstraction of DEE and the decomposition of the ethoxy radical have the largest influence. In separate experiments at 1.9 atm and 1340 K, it is shown that DEE inhibits the reactivity of an equimolar mixture of hydrogen and oxygen (1% of each).


Subject(s)
Ether/chemistry , Models, Chemical , Absorption , Hydroxides/chemistry , Kinetics , Lasers , Oxidation-Reduction , Spectrophotometry, Infrared
6.
Int J Obes (Lond) ; 32(12): 1841-7, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18936764

ABSTRACT

BACKGROUND: Several studies have reported increased fat oxidation with diacylglycerol (DAG) oil consumption. However, the effects of long-term DAG oil consumption on energy metabolism remain to be investigated. OBJECTIVE: The objective of this study was to compare the effects of 14 days of either DAG or triacylglycerol (TAG) oil consumption on substrate oxidation, energy expenditure (EE) and dietary fat oxidation. DESIGN: Eight males and six females participated in this randomized, double-blind, crossover feeding study. Each patient consumed the 14-day controlled test diet containing either 10 g day(-1) of DAG or TAG oil for acclimatization before a respiratory chamber measurement, followed by a 2-week washout period between diet treatments. Substrate oxidation and EE were measured in the respiratory chamber at the end of each dietary treatment. The patients consumed test oil as 15% of total caloric intake in the respiratory chamber (mean test oil intake was 36.1+/-6.6 g day(-1)). RESULTS: Twenty-four hour fat oxidation was significantly greater with 14 days of DAG oil consumption compared with TAG oil consumption (78.6+/-19.6 and 72.6+/-14.9 g day(-1), respectively, P<0.05). There were no differences in body weight or body composition between diet treatments. Dietary fat oxidation was determined using the recovery rate of (13)CO(2) in breath, and was significantly enhanced with DAG oil consumption compared with TAG oil consumption, measured over 22 h after ingestion of (13)C-labelled triolein. Resting metabolic rate (RMR) was significantly greater with DAG oil consumption compared with TAG oil consumption (1766+/-337 and 1680+/-316 kcal day(-1), respectively, P<0.05). CONCLUSION: Consumption of DAG oil for 14 days stimulates both fat oxidation and RMR compared with TAG oil consumption, which may explain the greater loss of body weight and body fat with DAG oil consumption that has been observed in weight-loss studies.


Subject(s)
Adipose Tissue/drug effects , Dietary Fats/metabolism , Diglycerides/pharmacology , Energy Metabolism/drug effects , Plant Oils/pharmacology , Triglycerides/pharmacology , Adult , Breath Tests , Carbon Dioxide/chemistry , Cross-Over Studies , Diglycerides/administration & dosage , Double-Blind Method , Fatty Acids, Monounsaturated , Female , Food , Humans , Male , Middle Aged , Overweight/metabolism , Oxidation-Reduction , Plant Oils/administration & dosage , Rapeseed Oil , Safflower Oil/pharmacology , Soybean Oil/pharmacology , Tokyo , Triglycerides/administration & dosage , alpha-Linolenic Acid/pharmacology
7.
Drug Chem Toxicol ; 29(2): 203-13, 2006.
Article in English | MEDLINE | ID: mdl-16707328

ABSTRACT

A post-treatment assay of the umu test was performed to detect genotoxicity of 10 phenylenediamine (PDA) derivatives using Salmonella typhimurium TA1535/pSK1002 with/without S9 mix. Seven chemicals (o-PDA, 4-chloro-o-PDA, 4-nitro-o-PDA, p-PDA, 2-chloro-p-PDA, 2-nitro-p-PDA, and 2,5-diaminotoluene) showed positive results with S9 mix, but three chemicals (m-PDA, 4-chloro-m-PDA, and 2,4-diaminotoluene) were negative with and without S9 mix. Four of 7 chemicals (o-PDA, 4-chloro-o-PDA, 4-nitro-o-PDA, and 2-nitro-p-PDA) that gave positive results with S9 mix were also positive without S9 mix. These results indicate that the genotoxicity of PDA derivative possessing m-position amino substituents was not detected in the umu post-treatment assay using TA1535/pSK1002.


Subject(s)
Mutagenicity Tests , Mutagens/toxicity , Phenylenediamines/toxicity , SOS Response, Genetics/drug effects , Salmonella/drug effects , Animals , Dose-Response Relationship, Drug , Male , Mutagens/classification , Phenylenediamines/chemistry , Phenylenediamines/classification , Rats , Rats, Sprague-Dawley , Ribosomal Protein S9 , Ribosomal Proteins , SOS Response, Genetics/genetics , Salmonella/genetics , Stereoisomerism , Structure-Activity Relationship
8.
J Investig Dermatol Symp Proc ; 6(1): 19-24, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11764280

ABSTRACT

We report here morphologic and biochemical evidence that melanosomes are distinct from lysosomes. Immunofluorescence analysis revealed that TRP-1, a melanosomal membrane protein, did not colocalize with lysosomal membrane proteins LAMP1 and LGP85 in melan-a cells. Wortmannin treatment of melanocytes enhanced the distinct compartmentalization of these melanosomal/lysosomal membrane proteins by the swelling of the endosomal-lysosomal systems. The heavily melanized melanosomes did not have an altered shape, which suggests a lesser degree of membrane dynamics of stage IV melanosomes. Terminal lysosomes loaded with TR-dextran are also distinct from melanosomes, thus indicating that melanosomes are isolated from the endocytic pathway that is a representative route to lysosomes. Because AP-3 mutation leads to mistargeting of both melanosome and lysosome membrane proteins, we propose that there is a late sorting step for melanosomes and lysosomes in melanocytes after AP-3 sorting.


Subject(s)
Lysosomes/metabolism , Melanocytes/metabolism , Melanosomes/metabolism , Oxidoreductases , Protein Transport/physiology , Androstadienes/pharmacology , Animals , Antigens, CD/metabolism , CD36 Antigens/metabolism , Enzyme Inhibitors/pharmacology , Lysosomal-Associated Membrane Protein 1 , Lysosomal Membrane Proteins , Melanocytes/drug effects , Melanocytes/physiology , Melanocytes/ultrastructure , Membrane Glycoproteins/metabolism , Mice , Proteins/metabolism , Tissue Distribution , Tumor Cells, Cultured , Vacuoles/physiology , Vacuoles/ultrastructure , Wortmannin
10.
J Biol Chem ; 274(43): 30756-63, 1999 Oct 22.
Article in English | MEDLINE | ID: mdl-10521465

ABSTRACT

The extra domain-A (EDA), present in fibronectin (FN) molecules arising from alternatively spliced transcripts, appears only during specific biological and pathogenic processes. However, its function is poorly understood. To define the physiologic role of this domain in joint connective tissue, the biological effects on rabbit cartilage explants, chondrocytes, and synovial cells were studied. A recombinant EDA protein (rEDA) increased proteoglycan release (3. 6-fold) in cartilage explant cultures and markedly induced production of matrix metalloproteinase (MMP)-1 in chondrocytes. In addition, rEDA induced MMP-1, MMP-3, and MMP-9 in synovial cells. These effects were elicited only by rEDA, while its neighboring type III repeats, III(11) or III(12), scarcely had any such effects. Interestingly, reorganization of F-actin stress fibers accompanied MMP-1 expression in synovial cells treated with rEDA, suggesting alteration of cellular phenotype. Subsequent Northern blotting revealed expression of pro-inflammatory cytokines, including interleukin (IL)-1alpha and IL-1beta, was induced by rEDA prior to MMP-1 expression. Delayed MMP-1 expression suggests that rEDA-induced IL-1s promote MMP-1 expression in an autocrine manner. This hypothesis is supported by the reduction of EDA-induced MMP-1 production by IL-1 receptor antagonist. The effect of EDA on MMP-1 production was reduced by connection with an adjacent type III repeat on either the NH(2) or COOH side of EDA and was abolished by connection on both sides of EDA, suggesting that exposure of either the NH(2) or COOH terminus of EDA domain by proteolytic cleavage releases the inducing activity. In agreement with these results, full-length cellular FN did not induce MMP-1 production. Furthermore, a 160-kDa EDA-positive FN fragment, which was purified from human placental tissue and corresponds to the region from NH(2) terminus through the EDA, induced MMP-1 production. Taken together, these results suggest that the EDA in FN fragments triggers alterations of cell physiology and plays a role in matrix degradation in joint connective tissue.


Subject(s)
Cartilage, Articular/metabolism , Fibronectins/genetics , Gene Expression Regulation, Enzymologic/physiology , Matrix Metalloproteinases/genetics , Proteoglycans/biosynthesis , Synovial Membrane/enzymology , Alternative Splicing , Animals , Cartilage, Articular/cytology , Cartilage, Articular/drug effects , Cells, Cultured , Fibronectins/chemistry , Fibronectins/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Humans , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/genetics , Organ Culture Techniques , RNA, Messenger/genetics , Rabbits , Recombinant Proteins/pharmacology , Synovial Membrane/cytology , Transcription, Genetic/drug effects
11.
Biochem Biophys Res Commun ; 255(1): 54-8, 1999 Feb 05.
Article in English | MEDLINE | ID: mdl-10082654

ABSTRACT

Lysosomal membrane glycoproteins carry targeting information in cytoplasmic regions. Two distinct targeting motifs in these regions, GY (glycine-tyrosine) and LI (leucine-isoleucine), have been identified and characterized. Accumulating evidence suggests that the adaptor complexes (AP-1, AP-2, and AP-3) recognize this information in cytoplasmic tails of transmembrane proteins. Here we report two different in vitro analyses (affinity beads and surface plasmon resonance) which revealed specific interaction between the cytoplasmic tail of LGP85 and AP-1 but not so with AP-2. We also noted requirement of the LI motif of the LGP85 tail in binding to the AP-1 complex. Our data and others which indicated the binding of AP-3 to the LIMP II (synonym of LGP85) tail suggest that the cytoplasmic tail of LGP85 interacts with AP-1 at the trans-Golgi network (TGN) and AP-3 at late endosomes, respectively. We propose that this sequential interaction between the lysosomal targeting signal and distinct APs along its transport pathway is responsible for the critical sorting of lysosomal membrane proteins and/or the potential proofreading system of mistargeted molecules.


Subject(s)
CD36 Antigens/metabolism , Lysosomes/metabolism , Membrane Glycoproteins , Membrane Proteins/metabolism , Monomeric Clathrin Assembly Proteins , Adaptor Protein Complex alpha Subunits , Adaptor Proteins, Vesicular Transport , Amino Acid Sequence , Animals , Binding Sites , Biological Transport , Clathrin/metabolism , Lysosomal Membrane Proteins , Molecular Sequence Data , Protein Binding , Rats
12.
Blood ; 93(1): 34-42, 1999 Jan 01.
Article in English | MEDLINE | ID: mdl-9864143

ABSTRACT

We examined the potential involvement of two CC chemokine receptors (CCRs), CCR-1 and CCR-3, in the functional activation of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4)-generated human peripheral blood monocyte-derived immature dendritic cells (DCs). Flow cytometric analysis showed that CCR-1, CCR-3, CCR-5, and CXC chemokine receptor (CXCR)-4 were expressed on the cell surface of monocyte-derived DCs. Treatment with a monoclonal antibody (MoAb) to either CCR-1 or CCR-3 but not MoAbs to CCR-5 and CXCR-4 abolished chemotactic migration of monocyte-derived DCs. The DCs treated with either the anti-CCR-1 MoAb or anti-CCR-3 MoAb were less efficient than untreated DCs in proliferation of allogeneic T cells (TCs) and TC-derived secretion of interferon-gamma (IFN-gamma). The homotypic aggregation of DCs and heterotypic aggregation of DCs with TCs were suppressed by the anti-CCR-1 MoAb or anti-CCR-3 MoAb. These results indicate that CCR-1 and CCR-3 specifically regulate interaction of TCs and DCs in the process of antigen presentation.


Subject(s)
Antigen-Presenting Cells/physiology , Chemokines, CC/metabolism , Dendritic Cells/physiology , Monocytes/physiology , Receptors, Chemokine/physiology , Antibodies, Monoclonal/pharmacology , Cell Differentiation , Cell Migration Inhibition , Cells, Cultured , Chemotaxis/immunology , Dendritic Cells/metabolism , Humans , Lymphocyte Activation/drug effects , Monocytes/metabolism , Receptors, CCR1 , Receptors, CCR3 , Receptors, Chemokine/biosynthesis , Receptors, Chemokine/immunology , T-Lymphocytes/immunology
13.
FEBS Lett ; 399(3): 272-6, 1996 Dec 16.
Article in English | MEDLINE | ID: mdl-8985161

ABSTRACT

A soluble recombinant CD59#77 (rCD59#77), consisting of 77 amino acids starting from the N terminus of membrane-bound CD59, was prepared using a gene expression system in CHO cells. The rCD59#77 preparation was composed of glycosylated and non-glycosylated forms (G and NG forms). Unexpectedly, NG form was 7 times more potent than G form in complement inhibitory activity. Postulating that sialic acids on G-form molecules make it difficult for rCD59#77 to access nascent membrane attack complexes on the cell surface, the sialic acids were removed by neuraminidase treatment. However, the inhibitory activity was not changed. Next, one of two putative N-glycosylation sites was mutated by substituting Gln18 for Asn18. The mutant, designated rCD59#77(N/Q), had no sugar moiety and was as active as the NG form of rCD59#77. These results suggest that the bulky sugar moiety at Asn18 is not necessary for the complement-inhibitory activity of rCD59 and actually hampers that function.


Subject(s)
CD59 Antigens/chemistry , Complement Inactivator Proteins/chemistry , Animals , CHO Cells , Cricetinae , Humans , Recombinant Proteins/chemistry
14.
Int J Hematol ; 63(3): 227-34, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8936336

ABSTRACT

We investigated the effect of high-dose intravenous gamma globulin therapy on the plasma level of macrophage-colony stimulating factor (M-CSF) level in 13 patients with chronic idiopathic thrombocytopenic purpura. M-CSF and interleukin-6 levels were determined by enzyme-linked immunosorbent assay. The mean +/- S.D. level of M-CSF in the patients was 1235 +/- 439 U/ml, and the level in 8 patients was higher than the mean + S.D. (903.6 U/ml) in normal controls. All 8 patients had steroid-refractory disease. M-CSF levels were significantly correlated with the serum levels of interleukin-6 (r = 0.66, P < 0.05). Interleukin-6 levels were also significantly raised in the high M-CSF group compared with the normal M-CSF group (P < 0.05). In the whole patient population, M-CSF levels decreased, but not significantly, after intravenous gamma globulin, while interleukin-6 decreased significantly. However, in the patients with high pretreatment M-CSF levels, both M-CSF and interleukin-6 decreased significantly after treatment (M-CSF, 4 weeks, P < 0.05; IL-6, 1 week, P < 0.05, 4 weeks, P < 0.01). These findings suggest that high-dose intravenous gamma globulin causes thrombocytosis by the decrease of M-CSF levels in idiopathic thrombocytopenic purpura.


Subject(s)
Immunoglobulins, Intravenous/administration & dosage , Macrophage Colony-Stimulating Factor/blood , Purpura, Thrombocytopenic, Idiopathic/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/blood
15.
Kansenshogaku Zasshi ; 70(4): 338-46, 1996 Apr.
Article in Japanese | MEDLINE | ID: mdl-8690948

ABSTRACT

We followed 54 HIV-1 carriers (44 asymptomatic carriers and 10 AIDS patients) by virus isolation and immunological examination and evaluated their usefulness for prognostication of the onset of symptoms. From 37 carriers (27 asymptomatic carriers and 10 symptomatic), 132 HIV-1 strains were isolated; the virus isolation rate was 60% in the asymptomatic carriers (AC) but 100% in the symptomatic. In the AC, the isolation rate was 54.5% in the group showing stable in the CD4+ level but 95.5% in the group showing a decrease in the CD4+ level. With progression of the disease, the culture time required for virus isolation was shortened, and the percentage of isolates showing infectivity to the T-cell line (MT-4 cells) increased. These findings suggest that the virus in the body is changed with progression of the disease to that showing rapid replication, T-cell tropic, and high pathogenicity. Indeed, progression of the disease was observed in all carriers in whom a highly pathogenic virus was detected; some developed the disease within 1 year, some showed temporary recovery in the CD4+ level after AZT administration followed by progression to ARC, and others showed a rapid decrease in the CD4+ level. In contrast, in carriers with only slightly pathogenic virus, the CD4+ level was maintained for a long period. These results suggest that the detection of a highly pathogenic virus is one of the most reliable marker for the prognostication of the onset of the disease. The detection of HIV-1 antigen in the plasma and a decrease in the gag antibody were also associated with the progression of the disease. However, the reliability of these markers seems to be lower than that of virus isolation.


Subject(s)
Acquired Immunodeficiency Syndrome/virology , Carrier State/virology , HIV-1/isolation & purification , Acquired Immunodeficiency Syndrome/diagnosis , Biomarkers , CD4 Antigens/blood , Carrier State/diagnosis , Follow-Up Studies , Humans , Prognosis
16.
Kansenshogaku Zasshi ; 70(4): 347-53, 1996 Apr.
Article in Japanese | MEDLINE | ID: mdl-8690949

ABSTRACT

We have reported on the investigation of 54 HIV-1 patients concerning the isolation and clinical marker in the preceding paper. We have attempted the analysis of the V3 and RT genes. HIV-1 from a patient who had rapidly taken a turn for the worse had basic amino acid at position 11 (Arg) and lost an acidic amino acid at position 25 (Gln) of V3. This sequence pattern was a distinguished feature of a virus with a rapid-high, syncytium inducing (SI) and T-cell-line tropic phenotype. In contrast, patients with no or mild clinical symptoms had sequences characterized as slow-low, non-synsytium inducing (NSI) and macrophage tropic. We then investigated the appearance of resistant to AZT and ddI. It was shown that the virulent virus obtained drug resistant variants faster than the wild type by analysis of the RT gene. We consider that these data concerning virus isolation and gene analysis are useful for prognosis and strategy for clinical therapy.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Genes, Viral/genetics , HIV-1/genetics , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/virology , Amino Acid Sequence , Antiviral Agents/therapeutic use , Base Sequence , Follow-Up Studies , Humans , Molecular Sequence Data , Prognosis , Zidovudine/therapeutic use
17.
Blood ; 87(1): 93-101, 1996 Jan 01.
Article in English | MEDLINE | ID: mdl-8547681

ABSTRACT

A receptor tyrosine kinase (RTK), TIE (tyrosine kinase that contains immunoglobulin-like loops and epidermal growth factor [EGF] homology domains), is expressed in vascular endothelial and hematopoietic cells. We generated monoclonal antibodies (MoAbs) against the extracellular domain of TIE and a polyclonal antibody against the TIE carboxyterminus and used them to analyze expression of TIE in hematopoietic cells. Western blotting detected two forms of TIE protein with a molecular mass of 135 and 130 kD in hematopoietic and endothelial cells. Northern blotting analysis revealed that TIE was expressed preferentially in undifferentiated cell lines, especially when megakaryocytic, but not erythroid differentiation was induced. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that TIE was predominantly expressed in the human hematopoietic progenitor fraction, CD34+ cells. Fluorescence-activated cell sorting (FACS) showed that 42% of CD34+ and 17% of KIT-positive (KIT+) cells were TIE-positive (TIE+). The majority (81%) of the primitive hematopoietic stem cells, CD34+CD38- cells, were TIE+. Assays of progenitor cells and long-term culture-initiating cells (LTC-IC) showed that the TIE+ fraction contained more primitive cells than the TIE- fraction. Some TIE+ cells were in the CD34- fraction, which were CD19+ and CD20+ (B cells). These findings indicate that TIE has a unique spectrum of expression in primitive hematopoietic stem cells and B cells. Although its ligand has not been identified, TIE and its ligand may establish a novel regulatory pathway not only in early hematopoiesis, but also in the differentiation and/or proliferation of B cells.


Subject(s)
B-Lymphocytes/enzymology , Hematopoietic Stem Cells/enzymology , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptors, Cell Surface/biosynthesis , Animals , Antibodies, Monoclonal/immunology , Base Sequence , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/pathology , Cell Differentiation , Cell Line , DNA, Complementary/genetics , Enzyme Induction , Fibroblasts/enzymology , Flow Cytometry , Humans , Leukemia, Erythroblastic, Acute/enzymology , Leukemia, Erythroblastic, Acute/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Liver Neoplasms/enzymology , Liver Neoplasms/pathology , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunology , Receptors, TIE , Tumor Cells, Cultured
18.
Am J Hematol ; 51(1): 37-44, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8571936

ABSTRACT

The efficacy of recombinant human interferon alpha-2b (rh IFN alpha-2b) in the treatment of steroid resistant idiopathic thrombocytopenic purpura (ITP) was studied in 50 cases. Forty-one patients treated with rh IFN alpha-2b three times a week, six of 18 (33.3%) in the low dose group (150 x 10(4)IU: 3 MIU) and four of 20 (20.0%) in the high dose group (300 x 10(4)IU: 3 MIU) responded with platelet counts increasing to above 50 x 10(9)/L. Because of the exacerbation of thrombocytopenia and nasal bleeding, treatment was discontinued within 2 weeks in three patients out of 41 cases. On the other hand, six of nine patients (66.7%) treated with 3 MIU of IFN alpha-2b once a week for 8 weeks showed satisfactory response. Treatment with either administration schedule did not result in sustaining platelet counts above 50 x 10(9)/L for a long time after treatment. The results indicate that once a week administration schedule of rh IFN alpha-2b is more efficacious for platelet counts increasing for short period in patients who failed to respond to steroid and other medications than other schedules. The maintenance of this treatment schedule will allow sustained increased platelet levels, resulting in relief of bleeding tendency, while also being cost effective in comparison with other IFN treatment schedules and achieving better patient compliance without flu-like symptoms.


Subject(s)
Immunologic Factors/therapeutic use , Interferon-alpha/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/therapy , Adolescent , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Child , Child, Preschool , Combined Modality Therapy , Drug Administration Schedule , Drug Resistance , Female , Humans , Immunologic Factors/administration & dosage , Infant , Interferon alpha-2 , Interferon-alpha/administration & dosage , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/surgery , Recombinant Proteins , Splenectomy , Treatment Outcome
19.
Nucl Med Biol ; 22(1): 71-6, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7735173

ABSTRACT

To experimentally assess the kinetics of platelets in thrombocytopenia, we constructed a canine model using 111In-oxine labeled autologous platelets and an intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion of radiolabeled autologous platelets into dogs, the peripheral platelet count and blood radioactivity level were examined, and the radioactivity in the liver, spleen and heart was determined with scintigraphic analysis. Thereafter, i.v. injection of 100 micrograms/kg of NNKY2-11 had no effect on platelet counts or the biodistribution of radiolabeled platelets. However, 200 and 300 micrograms/kg of MAb reduced the platelets, and the radioactivity of the liver and spleen augmented clearly after injection of MAb. Platelet radioactivity in serum, which had decreased after MAb infusion, did not recover, even when peripheral platelet counts returned to the normal levels, indicating that these new platelets might be derived from the platelet-storage pool or new thrombocytogenesis. This model of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the kinetics of platelets in thrombocytopenia.


Subject(s)
Antibodies, Monoclonal/immunology , Blood Platelets/physiology , Platelet Membrane Glycoproteins/immunology , Thrombocytopenia/blood , Animals , Dogs , Female , Indium Radioisotopes , Kinetics , Mice , Mice, Inbred BALB C , Platelet Count
20.
Cancer Genet Cytogenet ; 74(1): 35-9, 1994 May.
Article in English | MEDLINE | ID: mdl-8194045

ABSTRACT

The chromosome der(1;7)(q10;p10) consists of the short arm of chromosome 7 and the long arm of chromosome 1, and is a common abnormality in treatment-related leukemia and myelodysplastic syndrome. Here we describe a 39-year-old Japanese man with acute myeloblastic leukemia (FAB-M2) exhibiting t(8;21)(q22;q22). He entered complete remission after induction therapy, and intensification therapy including alkylating agents was subsequently continued for 3 years. The patient then developed pancytopenia; bone marrow aspiration revealed myelodysplastic syndrome exhibiting the der (1;7) chromosome. To our knowledge, this is the first reported case of such an abnormality in myelodysplastic syndrome secondary to acute myeloblastic leukemia with the 8;21 translocation.


Subject(s)
Anemia, Refractory, with Excess of Blasts/genetics , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 21 , Chromosomes, Human, Pair 7 , Chromosomes, Human, Pair 8 , Leukemia, Myeloid, Acute/genetics , Translocation, Genetic , Adult , Anemia, Refractory, with Excess of Blasts/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Humans , Karyotyping , Leukemia, Myeloid, Acute/drug therapy , Male
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