Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 114
Filter
1.
Heliyon ; 5(10): e02584, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31720446

ABSTRACT

Researches documenting comprehensively the prevalence of seed vivipary in relation to phenology, as well as its impact on production are scant. This article reports the results of investigations carried out during four cropping seasons to quantitatively document seed vivipary in the oleaginous bottle gourd (Lagenaria siceraria). Field experiments were conducted during the first and second cropping season of 2014 and 2015 at the experimental station of Nangui Abrogoua University (Abidjan, Côte d'Ivoire). The assessment of the prevalence of seed vivipary was carried out using 185 L. siceraria accessions collected in different ecological zones of Côte d'Ivoire. To examine the influence of fruit maturation time on seed vivipary, four accessions (two viviparous and two non-viviparous) were cropped and harvested at 30 and 50 days after fertilization (DAF), complete whiteness of plants (CPW) and after 60 days of storage of fruits harvested on plants completely withered (CPWS). Finally, a comparative analysis of seed yield and its main components was conducted using four accessions including two highly viviparous and two non-viviparous. The results on seed vivipary prevalence showed that the oleaginous form of L. siceraria is highly susceptible and allowed the classification of the 185 accessions analyzed into three groups: non-viviparous (2.16%), viviparous (89.19%) and highly viviparous accessions (8.65%). No precocious seed germination was observed in non-viviparous accessions during fruit maturation stage. The fruits of highly viviparous accessions harvested at 30 DAF showed no precocious seed germination while 3.35-17.89% of fruits bearing viviparous seed were observed at 50 DAF. Plants from highly viviparous fruits showed significantly low yields compared those from non-viviparous fruits. These results suggested that an efficient control of seed vivipary allowing a quantitative and qualitative improvement of yield in the oilseed bottle gourd can be ensured by the selection of vivipary-tolerant genotypes and appropriate planning of the harvest time.

2.
Chaos ; 24(3): 033115, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25273195

ABSTRACT

The phase dynamics of Josephson junctions (JJs) under external electromagnetic radiation is studied through numerical simulations. Current-voltage characteristics, Lyapunov exponents, and Poincaré sections are analyzed in detail. It is found that the subharmonic Shapiro steps at certain parameters are separated by structured chaotic windows. By performing a linear regression on the linear part of the data, a fractal dimension of D = 0.868 is obtained, with an uncertainty of ±0.012. The chaotic regions exhibit scaling similarity, and it is shown that the devil's staircase of the system can form a backbone that unifies and explains the highly correlated and structured chaotic behavior. These features suggest a system possessing multiple complete devil's staircases. The onset of chaos for subharmonic steps occurs through the Feigenbaum period doubling scenario. Universality in the sequence of periodic windows is also demonstrated. Finally, the influence of the radiation and JJ parameters on the structured chaos is investigated, and it is concluded that the structured chaos is a stable formation over a wide range of parameter values.

3.
J Sci Food Agric ; 91(11): 2073-80, 2011 Aug 30.
Article in English | MEDLINE | ID: mdl-21547916

ABSTRACT

BACKGROUND: The stage of fruit ripeness at the time of harvest determines the final quality of ripe fruit. In this study, changes in the chemical composition of seed kernels from the oleaginous gourd Lagenaria siceraria (Molina) Standl. during maturation were evaluated to determine the best time to harvest the berries. Two cultivars (round and oval berry) were studied at three maturation stages (30 and 50 days after fruit set (DAFS) and complete plant whiteness (CPW)). RESULTS: Seed kernels were rich in oil (527.2-544.6 g kg(-1)), protein (402.8-403.3 g kg(-1)), minerals and energy. Maturation influenced the chemical compounds of the two cultivars differently. Best quantities of these components were reached at 50 DAFS. However, protein bioavailability was better at 30 DAFS and CPW in the round and oval berry cultivars respectively. Lagenaria siceraria oils were of good quality, containing an abundance of essential fatty acids (647.2-667.0 g kg(-1)). CONCLUSION: Both cultivars of L. siceraria should be harvested at 50 DAFS owing to the good nutritional properties of their seeds and oils. However, to obtain best-quality proteins, round and oval berry cultivars should be harvested at 30 DAFS and CPW respectively. The results of this study will be useful in reducing the production time of fruits and improving the nutritional quality of their seeds.


Subject(s)
Cucurbitaceae/chemistry , Dietary Proteins/analysis , Fruit/chemistry , Fruit/growth & development , Plant Oils/chemistry , Seeds/chemistry , Seeds/growth & development , Chemical Phenomena , Cote d'Ivoire , Cucurbitaceae/growth & development , Dietary Carbohydrates/analysis , Dietary Fats/analysis , Fatty Acids, Essential/analysis , Hydrogen-Ion Concentration , Minerals/analysis , Nutritive Value , Peroxides/analysis , Pigmentation , Quality Control , Species Specificity , Time Factors , Water/analysis
4.
Gene Ther ; 18(9): 874-83, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21430784

ABSTRACT

This report describes generation of dendritic cells (DCs) and macrophages from human induced pluripotent stem (iPS) cells. iPS cell-derived DC (iPS-DC) exhibited the morphology of typical DC and function of T-cell stimulation and antigen presentation. iPS-DC loaded with cytomegalovirus (CMV) peptide induced vigorous expansion of CMV-specific autologous CD8+ T cells. Macrophages (iPS-MP) with activity of zymosan phagocytosis and C5a-induced chemotaxis were also generated from iPS cells. Genetically modified iPS-MPs were generated by the introduction of expression vectors into undifferentiated iPS cells, isolation of transfectant iPS cell clone and subsequent differentiation. By this procedure, we generated iPS-MP expressing a membrane-bound form of single chain antibody (scFv) specific to amyloid ß (Aß), the causal protein of Alzheimer's disease. The scFv-transfectant iPS-MP exhibited efficient Aß-specific phagocytosis activity. iPS-MP expressing CD20-specific scFv engulfed and killed BALL-1 B-cell leukemia cells. Anti-BALL-1 effect of iPS-MP in vivo was demonstrated in a xeno-transplantation model using severe combined immunodeficient mice. In addition, we established a xeno-free culture protocol to generate iPS-DC and iPS-MP. Collectively, we demonstrated the possibility of application of iPS-DC and macrophages to cell therapy.


Subject(s)
Cell- and Tissue-Based Therapy/methods , Dendritic Cells/cytology , Induced Pluripotent Stem Cells/cytology , Macrophages/cytology , Cell Differentiation , Cell Line, Tumor , Humans , Leukemia, B-Cell/immunology , Lymphocyte Activation , Phagocytosis , Transfection
5.
Br J Cancer ; 104(2): 300-7, 2011 Jan 18.
Article in English | MEDLINE | ID: mdl-21179034

ABSTRACT

BACKGROUND: Identification of tumour-associated antigens (TAAs) that induce cytotoxic T lymphocytes (CTLs) specific to cancer cells is critical for the development of anticancer immunotherapy. In this study, we aimed at identifying a novel TAA of pancreatic cancer for immunotherapy. METHODS: On the basis of the genome-wide cDNA microarray analysis, we focused on KIF20A (also known as RAB6KIFL/MKlp2) as a candidate TAA in pancreatic cancer cells. The HLA-A2 (A*02:01)-restricted CTL epitopes of KIF20A were identified using HLA-A2 transgenic mice (Tgm) and the peptides were examined to check whether they could generate human CTLs exhibiting cytotoxic responses against KIF20A(+), HLA-A2(+) tumour cells in vitro. RESULTS: KIF20A was overexpressed in pancreatic cancer and in some other malignancies, but not in their non-cancerous counterparts and many normal adult tissues. We found that KIF20A-2 (p12-20, LLSDDDVVV), KIF20A-8 (p809-817, CIAEQYHTV), and KIF20A-28 (p284-293, AQPDTAPLPV) peptides could induce HLA-A2-restricted CTLs in HLA-A2 Tgm without causing autoimmunity. Peptide-reactive human CTLs were generated from peripheral blood mononuclear cells of HLA-A2(+) healthy donors by in vitro stimulation with the three peptides, and those CTLs successfully exhibited cytotoxic responses to cancer cells expressing both KIF20A and HLA-A2. CONCLUSION: KIF20A is a novel promising candidate for anticancer immunotherapeutic target for pancreatic cancers.


Subject(s)
Epitopes/immunology , HLA-A2 Antigen/immunology , Kinesins/immunology , Pancreatic Neoplasms/immunology , T-Lymphocytes, Cytotoxic/immunology , Amino Acid Sequence , Animals , Base Sequence , Blotting, Western , DNA Primers , Epitopes/chemistry , HLA-A2 Antigen/chemistry , Humans , Immunohistochemistry , Mice , Mice, Knockout , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction
6.
Int J Immunopathol Pharmacol ; 23(1): 165-77, 2010.
Article in English | MEDLINE | ID: mdl-20378004

ABSTRACT

Severe acute respiratory syndrome (SARS) spread during the winter of 2003, and attempts have been made to develop vaccines against SARS corona virus (SARS-CoV). The present study provides a strategy to rapidly identify SARS-CoV-derived antigenic peptides recognized by HLA-A2-restricted cytotoxic T lymphocytes (CTLs). Forty-three candidate peptides having HLA-A2-binding motifs were selected in silico and HLA-A2/Db chimeric MHC class I-transgenic mice were immunized with these peptides and a new derivative of muramyl dipeptide that can induce upregulation of HLA-DR, CD80, CD86, and CD40 in human CD14+ antigen presenting cells, was administered as an adjuvant. Six HLAA2-restricted mouse CTL epitopes were identified, including two new epitopes which have never been reported before. One of the novel peptides was naturally processed and successfully induced HLAA2-restricted specific CTLs in both HLA transgenic mice and healthy donors. The method was useful, convenient and efficient for rapid identification of CTL epitopes derived from SARS-CoV proteins and will be possibly applicable for other pathogens to develop a peptide-based vaccine.


Subject(s)
Acetylmuramyl-Alanyl-Isoglutamine/analogs & derivatives , Adjuvants, Immunologic/pharmacology , HLA-A2 Antigen/immunology , Membrane Glycoproteins/immunology , T-Lymphocytes, Cytotoxic/immunology , Viral Envelope Proteins/immunology , Animals , Antigen Presentation , Antigens, Viral/immunology , Epitopes, T-Lymphocyte , Humans , Immunization , Mice , Mice, Inbred C57BL , Mice, Transgenic , Spike Glycoprotein, Coronavirus , Viral Vaccines/immunology
7.
Cancer Gene Ther ; 13(3): 298-305, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16110311

ABSTRACT

The altered expression of both p53 and erbB2 is strongly related to the disease status and the outcome of bladder cancers. We examined the antitumor efficacy by the modulation of these genetic alterations with a newly designed dual-gene-expressing adenovirus (Ad-p53/erbB2Rz), which expresses p53 and anti-erbB2 ribozyme simultaneously in human bladder cancer cells. Cell growth inhibition efficacy along with biological responses of this virus was compared with other viral vectors (Ad-p53, which expresses wild-type p53 cDNA, and Ad-erbB2Rz, which expresses anti-erbB2 ribozyme, solely or in combination). Sufficient transgene expression in targeted cells and the altered expression of the targeted genes and their encoded proteins were obtained by each therapeutic vector. Each of the three therapeutic viral vectors inhibited bladder cancer cell growth, and the putative additive antitumor effect was shown by the combination of two of the therapeutic vectors. Furthermore, Ad-p53/erbB2Rz had superior therapeutic efficacy when the same titers of viruses were infected. Nonspecific vector-related toxicity was minimized by reducing the total amount of viral titers by using the dual-gene-expressing adenovirus. Modulation of multiple genetic abnormalities might enhance the therapeutic efficacy, and vector-related toxicity could be minimized when the total amount of viral titers are reduced.


Subject(s)
Adenoviridae/genetics , RNA, Catalytic/therapeutic use , Receptor, ErbB-2/genetics , Tumor Suppressor Protein p53/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/therapy , Apoptosis , Cell Survival , Combined Modality Therapy , Female , Gene Transfer Techniques , Genetic Therapy , Genetic Vectors/therapeutic use , Humans , Tumor Cells, Cultured , Tumor Suppressor Protein p53/metabolism , Urinary Bladder Neoplasms/metabolism
8.
Article in French | AIM (Africa) | ID: biblio-1264270

ABSTRACT

La devaluation du franc CFA en 1994 a entraine une flambee des prix des medicaments. La solution ivoirienne fut l'intensification; en accord avec des textes legislatifs; de la politique des medicaments generiques. Le but de notre travail est dans un premier temps de recenser les classes pharmaco- therapeutiques des medicaments generiques proposes afin d'apprecier si ceux-ci sont adaptes a la liste des medicaments essentiels du Ministere charge de la sante puis dans un deuxieme temps d'etudier lescaracteristiques pharmacologiques decrits dans les dossiers d'enregistrement de ces medicaments generiques afin d'apprecier leur interchangeabilite avec les specialites de reference. A cet effet; nous avons procede a une etude transversale descriptive portant sur les dossiers techniques et administratifs de 384 medicaments generiques enregistres en Cote d'Ivoire. Il ressort de cette analyse que les medicaments generiques sont majoritairement des antibiotiques; des antiinflammatoires non steroidiens ou desantiparasitaires. Leur mode de preparation est decrit; les matieres premieres ainsi que les produits finis sont controlees et ces generiques ont une bonne stabilite et une bonne etancheite. Si la conformite de la forme galenique est presque exclusivement respectee; il n'en est pas ainsi pour la composition qualitative et quantitative en principe actif ; en effet; pour les principes actifs sous forme de sels; dans 18des cas le sel n'est pas identique a celui de la specialite d'origine ; de meme; 7.6des generiques - sels ne iberent pas la meme quantite de principe actif base que la specialite de reference. Il y a quelques fois conformite des excipients ; toutefois; dans 14des cas; les excipients a effet notoire presents dans la specialite de reference medicament generique


Subject(s)
Cote d'Ivoire , Drugs, Generic
9.
Article in French | AIM (Africa) | ID: biblio-1264271

ABSTRACT

L'interet de plus en plus croissant de la communaute internationale a l'egard des therapeutiques traditionnelles et la place de la medecine traditionnelle dans la demande de soins necessite de la part des autorites africaines de creer un cadre juridique pour une meilleure integration de la medecine dans les systemes conventionnels de sante. Aussi compte tenu de la place du medicament dans l'offre de sante; nous est-il paru opportun d'analyser un modele simplifie d'enregistrement des medicaments tel celui des medicaments generiques afin d'en evaluer l'adaptabilite aux medicaments traditionnels ameliores (MTA). Notre methodologie a consiste a recueillir aupres des administrations ubliques les textes legislatifs et reglementaires concernant les medicaments generiques et leurs conditions d'enregistrement en Cote d'Ivoire. L'analyse critique de ces dispositions mises en rapport avec les specificites de ces medicaments issus de la pharmacopee africaine a ete effectuee. Il ressort de ce travail que malgre la simplification de la procedure d'enregistrement des medicaments generiques; son adaptabilite aux MTA demeure encore problematique. En effet les etudes pharmacologiques; galeniques; toxicologiques et les essais cliniques restent difficiles a mettre en oeuvre conformement aux exigences internationales en ce qui concerne de tels medicaments. Il reste donc ux africains d'innover par la mise en place d'une reglementation souple qui tout en assurant une securite d'utilisation aux patients; permettrait un enregistrement facile des edicaments issus de la pharmacopee africaine


Subject(s)
Cote d'Ivoire , Drugs, Generic , Pharmacopoeia
10.
Acta Radiol ; 43(4): 433-40, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12225490

ABSTRACT

PURPOSE: To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. MATERIAL AND METHODS: Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. RESULTS: Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. CONCLUSION: Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors.


Subject(s)
Electron Spin Resonance Spectroscopy , Magnetic Resonance Imaging , Neoplasms, Experimental/diagnosis , Animals , Contrast Media , Feasibility Studies , Female , Humans , Maleates/pharmacology , Mice , Mice, Inbred C3H , Neoplasms, Experimental/metabolism , Nitric Oxide , Oxidation-Reduction , Phantoms, Imaging
11.
Mol Urol ; 5(2): 53-8, 2001.
Article in English | MEDLINE | ID: mdl-11690548

ABSTRACT

BACKGROUND: Altered expression of p53 has been described in nearly half of bladder cancers, and p53 mutations are presumed to play a role in the multistep progression of these tumors. MATERIALS AND METHODS: The incidence of mutation in the p53 gene and its correlation with histopathologic findings and patient survival were evaluated in 105 Japanese patients with bladder cancer. Laboratory experiments were also performed to confirm the infectivity and efficacy in tumor growth inhibition of an adenovirus expressing wild-type p53 in EJ bladder cancer cells. RESULTS: Mutations of p53 were observed in 38 bladder cancer specimens (36%), with a significantly higher incidence of mutation being seen in tumors of higher stage and grade. The overall survival was worse in patients with the p53 mutation. In laboratory experiments, adenoviral vectors infected bladder cancer cells in a dose- and cell density-dependent manner. The adenovirus-mediated transduction of wild-type p53 resulted in dose-dependent growth inhibition of bladder cancer cells in vitro. No significant cytotoxicity was observed after infection by a control adenovirus. CONCLUSION: Transduction of wild-type p53 might be a potential therapeutic option for bladder cancer.


Subject(s)
Adenoviridae/genetics , Genes, p53 , Genetic Therapy , Genetic Vectors , Transduction, Genetic , Urinary Bladder Neoplasms/genetics , Apoptosis , Cell Division , Cell Separation , Dose-Response Relationship, Drug , Flow Cytometry , Humans , Japan , Mutation , Polymerase Chain Reaction/methods , Polymorphism, Single-Stranded Conformational , Survival Rate , Tumor Cells, Cultured , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/therapy
12.
Mol Urol ; 5(2): 71-8, 2001.
Article in English | MEDLINE | ID: mdl-11690551

ABSTRACT

BACKGROUND AND PURPOSE: Programmed cell death is a genetically regulated pathway that is altered in many cancers. This process is, in part, regulated by the bcl-2 oncogene. Antisense oligodeoxynucleotides (ODNs) targeted to specific oncogenes have been used with some therapeutic success in animal models of leukemia and melanoma cells and human Hodgkin's lymphoma. We evaluated the effects of antisense ODNs targeted to the bcl-2 oncogene on the proliferation of human renal-cell carcinoma (RCC) cells in vitro and on the growth of human RCC xenografts in BALBc nude (nu/nu) mice. MATERIALS AND METHODS: Expression bcl-2 mRNA in five RCC cell lines (ACHN, Caki-1, RCZ, RCW, and OS-RC-2) was analyzed by reverse transcriptase-polymerase chain reaction. The effects of phosphorothioated ODNs containing human bcl-2 sense and bcl-2 antisense sequences that were transfected with Lipofectin on the proliferation and viability of cultures of established human RCC cell lines were determined by MTS assay. The expression of Bcl-2 protein in ACHN tumor cells following antisense bcl-2 (AS2) ODN treatment was evaluated by Western blot analysis, and the extent of apoptosis in these cells was determined by fluorescence-activated cell sorter (FACS) analysis. The antitumor activity in ACHN xenografts in nu/nu mice was monitored by measuring differences in tumor weight in treated and control mice. RESULTS: Expression of bcl-2 mRNA was detected in all five RCC lines. Treatment with antisense bcl-2 ODNs inhibited the growth of all tested RCC cells and decreased Bcl-2 protein expression in ACHN cells. The AS2 antisense ODN complementary to the coding region of bcl-2 mRNA showed a superior antiproliferative effect compared with AS1 ODN complementary to the translation initiation region. Inhibition by antisense bcl-2 ODNs of ACHN cells was dose dependent. The FACS analysis revealed that growth inhibition was associated with the induction of programmed cell death. In vivo, AS2 ODN antitumor activity was noted in locally injected groups. CONCLUSIONS: Treatment of human RCC with antisense ODNs targeted to bcl-2 inhibits growth and is associated with the induction of programmed cell death. These results suggest therapeutic use of antisense bcl2 in the treatment of RCC.


Subject(s)
Carcinoma, Renal Cell/therapy , Genes, bcl-2 , Kidney Neoplasms/therapy , Oligodeoxyribonucleotides, Antisense/therapeutic use , Thionucleotides/therapeutic use , Animals , Apoptosis/physiology , Carcinoma, Renal Cell/pathology , Cell Division/physiology , Cell Separation , Cell Transplantation , Flow Cytometry , Genetic Therapy , Humans , Kidney Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Oligodeoxyribonucleotides, Antisense/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Thionucleotides/genetics , Transfection , Transplantation, Heterologous , Tumor Cells, Cultured
13.
J Endourol ; 15(7): 729-34, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11697406

ABSTRACT

PURPOSE: To evaluate the efficacy and invasiveness of retroperitoneoscopic radical nephrectomy for renal-cell carcinoma (RCC) in patients with chronic renal failure (CRF), a group known to have relatively high surgical risk. PATIENTS AND METHODS: Between May 1996 and September 1999, six CRF patients maintained on hemodialysis underwent retroperitoneoscopic radical nephrectomy for clinically localized RCC by the posterior lumber approach. The excised kidneys were evacuated via a posterior skin incision (5 cm) between two port sites; the muscle layers were not incised. RESULTS: The procedure was completed in all patients with no major complications. The mean operative time was 162 (range 135-210) minutes, and the estimated blood loss was 58 (15-100) mL; none of the patients required a blood transfusion. Regular hemodialysis was restarted on postoperative day 2 or 3. CONCLUSIONS: This procedure seems to be minimally invasive and suitable for the treatment of small RCC in atrophic kidneys, especially in patients with CRF.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Failure, Chronic/complications , Kidney Neoplasms/surgery , Nephrectomy/methods , Atrophy , Carcinoma, Renal Cell/complications , Female , Humans , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/therapy , Kidney Neoplasms/complications , Lumbar Vertebrae , Male , Middle Aged , Minimally Invasive Surgical Procedures , Renal Dialysis , Retroperitoneal Space/surgery , Treatment Outcome
14.
Tissue Antigens ; 57(5): 447-56, 2001 May.
Article in English | MEDLINE | ID: mdl-11556969

ABSTRACT

In Japanese, susceptibility to the conventional form of multiple sclerosis (C-MS) is associated with the HLA-DRB1*1501-DRB5*0101 haplotype while susceptibility to the opticospinal form of MS (OS-MS) is associated with HLA-DPA1*0202-DPB1*0501. To clarify the characteristics of T cells autoreactive to myelin proteins in each MS subtype, we established T-cell lines reactive to such myelin antigens as myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) from 5 of 10 OS-MS patients, 6 of 11 C-MS patients and 7 of 13 healthy controls (HCs), and T-cell epitopes and their restriction molecules were determined. We found that (a) intermolecular epitope spreading was found to be significantly more frequent in MS patients than in HCs (P=0.0128), (b) intramolecular epitope spreading also tended to occur more frequently in MS patients than in HCs (P=0.0584), (c) in OS-MS, HLA-DR-restricted and MOG-autoreactive T cells were more frequently established as compared with those reactive to MBP or PLP epitopes and (d) in C-MS, HLA-DQ-restricted and PLP-autoreactive T cells dominated those autoreactive to MBP or MOG epitopes. A DPB1*0501-restricted MBP-reactive T-cell clone from a patient with OS-MS provided evidence that the first HLA class II anchor amino acid of peptide bound to disease-susceptible DP5 molecule was distinct from that for the DR2 molecule. Taken together, these differences in specificities of myelin-autoreactive T cells between C-MS and OS-MS as well as the difference in the anchor motif of the binding peptides between each MS subtype-susceptible HLA class II molecule may contribute to the development of distinct clinical phenotypes.


Subject(s)
Lymphocyte Activation/immunology , Multiple Sclerosis/immunology , Multiple Sclerosis/pathology , Myelin Proteins/immunology , Optic Nerve/pathology , Peptide Fragments/immunology , Spinal Cord/pathology , T-Lymphocytes/immunology , Adult , Amino Acid Sequence , Autoantibodies/biosynthesis , Clone Cells , Epitope Mapping/methods , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , Female , HLA-DP Antigens/immunology , Humans , Male , Middle Aged , Molecular Sequence Data , Myelin Basic Protein/immunology , Myelin Proteolipid Protein/immunology , Myelin-Associated Glycoprotein/immunology , Myelin-Oligodendrocyte Glycoprotein
15.
J Biol Chem ; 276(47): 44275-83, 2001 Nov 23.
Article in English | MEDLINE | ID: mdl-11557768

ABSTRACT

Several distinct regions of the integrin alpha(IIb) subunit have been implicated in ligand binding. To localize the ligand binding sites in alpha(IIb), we swapped all 27 predicted loops with the corresponding sequences of alpha(4) or alpha(5). 19 of the 27 swapping mutations had no effect on binding to both fibrinogen and ligand-mimetic antibodies (e.g. LJ-CP3), suggesting that these regions do not contain major ligand binding sites. In contrast, swapping the remaining 8 predicted loops completely blocked ligand binding. Ala scanning mutagenesis of these critical predicted loops identified more than 30 discontinuous residues in repeats 2-4 and at the boundary between repeats 4 and 5 as critical for ligand binding. Interestingly, these residues are clustered in the predicted beta-propeller model, consistent with this model. Most of the critical residues are located at the edge of the upper face of the propeller, and several critical residues are located on the side of the propeller domain. None of the predicted loops in repeats 1, 6, and 7, and none of the four putative Ca(2+)-binding predicted loops on the lower surface of the beta-propeller were important for ligand binding. The results map an important ligand binding interface at the edge of the top and on the side of the beta-propeller toroid, centering on repeat 3.


Subject(s)
Amino Acids/metabolism , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Amino Acid Sequence , Animals , CHO Cells , Cricetinae , Fibrinogen/metabolism , Humans , Ligands , Models, Molecular , Molecular Sequence Data , Mutagenesis , Platelet Glycoprotein GPIIb-IIIa Complex/chemistry , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Protein Binding , Protein Conformation , Sequence Homology, Amino Acid
16.
Biotech Histochem ; 76(3): 133-6, 2001 May.
Article in English | MEDLINE | ID: mdl-11475316

ABSTRACT

The membrane filter technique for smear specimens of tumors in bromodeoxyuridine (BrdU) immunochemistry is described. The staining results of Raji cells processed using the filter technique was compared with that obtained by the conventional cytospin method. Although the BrdU mean labeling index (LI) for in cytospin specimens was almost the same as the LI in membrane filter specimens, filter specimens showed excellent staining and less cell destruction compared with those processed by cytospin. Small amounts of tumor specimens such as squamous cell carcinoma and polymorphous low-grade adenocarcinoma also were processed using the membrane filter appliance. For squamous cell carcinoma, the LI for the filter specimens was 5.36+/-0.38 and that of the paraffin sections was 5.56+/-0.38. The membrane filter technique provided relatively undamaged specimens for exfoliative cytology and will be useful for immunohistochemical evaluation of tumor cells and for routine, noninvasive cytological screening.


Subject(s)
Bromodeoxyuridine , Cytological Techniques/methods , Staining and Labeling/methods , Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Humans , Immunochemistry/methods , Jaw Neoplasms/pathology , Membranes, Artificial , Mouth Neoplasms/pathology , Tumor Cells, Cultured
17.
Eur J Nucl Med ; 28(4): 522-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11357504

ABSTRACT

The purpose of the present study was to compare scintimammography using technetium-99m hexakis 2-methoxyisobutylisonitrile (MIBI) with that using 99mTc-hydroxymethylene diphosphonate (HMDP) in the detection of breast cancer and its axillary lesions. The study population comprised 50 consecutive females with breast cancer who were scheduled for surgery. All patients underwent scintimammography with 99mTc-MIBI and 99mTc-HMDP. The images were acquired 5 min (early) and 2 h (delayed) after injection of each radiopharmaceutical. Regions of interest were placed over the breast tumour (T), the axillary lesion (A) and the normal ipsilateral breast tissue (N). The two count ratios were calculated, i.e. the tumour to normal breast tissue ratio (T/N) and the axillary lymph node to normal breast tissue ratio (A/N). For the breast tumours, using 99mTc-MIBI the positive rate was 86% (43/50) for the early and 72% (36/50) for the delayed images. The corresponding values using 99mTc-HMDP were 72% (36/50) and 40% (20/50), respectively. Histopathological examination revealed metastatic lymph node involvement in 22 patients. For the axillary lesions, using 99mTc-MIBI the positive rate was 72.7% (16/22) for the early and 54.5% (12/22) for the delayed images. Using 99mTc-HMDP, the positive rate was only 18.2% (4/22) for the early and 4.5% (1/22) for the delayed images. Using 99mTc-MIBI, the mean T/N (+/- SD) ratios on early and delayed images were 2.69 +/- 1.64 and 2.03 +/- 1.16, respectively, and the mean A/N (+/- SD) ratios on early and delayed images were 2.20 +/- 1.23 and 1.80 +/- 1.20, respectively. The corresponding values using 99mTc-HMDP were 1.77 +/- 0.91, 1.42 +/- 0.72, 1.27 +/- 0.63 and 1.08 +/- 0.25, respectively. The T/N and A/N ratios on the early and delayed 99mTc-MIBI images were both significantly higher than those obtained using 99mTc-HMDP. 99mTc-MIBI scintimammography is more sensitive than 99mTc-HMDP scintimammography for the detection of breast cancer and its axillary lymph node metastases.


Subject(s)
Axilla/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Radiopharmaceuticals , Technetium Tc 99m Medronate/analogs & derivatives , Technetium Tc 99m Sestamibi , Adult , Aged , Female , Humans , Lymphatic Metastasis/diagnostic imaging , Mammography , Middle Aged , Radionuclide Imaging
18.
Surg Today ; 31(3): 222-4, 2001.
Article in English | MEDLINE | ID: mdl-11318124

ABSTRACT

We report an unusual case of spontaneous rupture of a parathyroid adenoma causing cervical hemorrhage. A 60-year-old woman presented to our hospital after the sudden development of extensive ecchymosis of her neck and upper anterior chest wall. Computed tomography (CT) scanning revealed a hematoma in the left retrotracheal space, and laboratory examinations revealed significant hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone. Primary hyperparathyroidism was diagnosed, but it was not until the hematoma had subsided, 4 months after her initial presentation, that a parathyroid adenoma was revealed by CT. An operation was performed, and a parathyroid adenoma with hemosiderin deposition was histologically diagnosed. Although this phenomenon is unusual, all endocrine surgeons should be well aware of the possibility of its occurrence.


Subject(s)
Adenoma/surgery , Hemorrhage/surgery , Parathyroid Neoplasms/surgery , Adenoma/diagnosis , Adenoma/pathology , Female , Hemorrhage/diagnosis , Hemorrhage/pathology , Humans , Middle Aged , Neck , Parathyroid Glands/pathology , Parathyroid Neoplasms/diagnosis , Parathyroid Neoplasms/pathology , Parathyroidectomy , Rupture, Spontaneous , Tomography, X-Ray Computed
19.
Surg Today ; 31(10): 899-903, 2001.
Article in English | MEDLINE | ID: mdl-11759886

ABSTRACT

Adenomyoepithelioma of the breast is a rare lesion, and has a bicellular pattern of epithelial and myoepithelial cells which are regularly distributed in the tubular structures based on the histologic and ultrastructural features. It is thought to be a benign or a low-grade malignant disease. We herein describe a case of malignant adenomyoepithelioma of the breast with lung metastases in an 86-year-old woman. A primary massive tumor in the left breast grew rapidly within a short period of time. A simple mastectomy with sampling of the axillary lymph nodes was performed. The obtained lymph nodes did not include any metastatic lesions. Malignancy was evidenced by the presence of a high mitotic rate and severe nuclear atypia. Three months after the operation, radiology showed multiple lung metastases, and the patient died 2 weeks thereafter. Reviewing the literature, nine similar cases were reported, and the prognosis of malignant adenomyoepithelioma of the breast with distant metastases was very poor with the time of recurrence varying after initial treatments. Malignant adenomyoepithelioma should be followed up with careful screening for distant metastases.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Adenoid Cystic/secondary , Lung Neoplasms/secondary , Aged , Aged, 80 and over , Female , Humans
20.
Jpn J Clin Oncol ; 31(11): 541-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11773262

ABSTRACT

BACKGROUND: The optimal protocol for combining high dose rate brachytherapy and external beam irradiation as treatment for localized prostate cancer is unknown. Toxicity rates and clinical and biochemical outcomes should be evaluated to validate the current treatment protocol. METHODS: Fifty-eight patients were treated for prostate cancer with high dose rate brachytherapy followed by 30 Gy of external beam radiation therapy. Toxicity during treatment and for 12-18 months thereafter, and treatment-related morbidity, were evaluated. Physician-assessed treatment-related toxicity was graded at the time of occurrence using the Radiation Therapy Oncology Group morbidity criteria. Four separate self-administered questionnaires were used to collect longitudinally demographic data and general and prostate disease-related measures of quality of life. RESULTS: Various degrees of rectal bleeding due to radiation proctitis were experienced by 13 patients (22%) at a median time of 11 months. Two of these patients needed hospitalization to undergo laser coagulation of the rectal mucosa. Study patients had statistically significant decreases in five SF-36 domains during the first month of treatment. All measures recovered by 12 months. Sexual function was not affected by irradiation. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment but later recovered to baseline levels. Physician-assessed RTOG scores failed to detect these changes. CONCLUSIONS: Morbidity associated with combined radiation therapy was greatest during the first month of treatment and affected quality of life significantly. Most measures recovered to baseline levels by 12 months following radiation therapy. Although the current protocol appears acceptable, measures should be taken to decrease treatment-related morbidity further.


Subject(s)
Brachytherapy/adverse effects , Prostatic Neoplasms/radiotherapy , Quality of Life , Radiotherapy/adverse effects , Adult , Aged , Hemorrhage/epidemiology , Humans , Male , Middle Aged , Prostatic Neoplasms/psychology , Radiotherapy Dosage , Rectal Diseases/epidemiology , Urinary Retention/epidemiology , Urination Disorders/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL
...