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1.
Med Oral Patol Oral Cir Bucal ; 22(6): e788-e795, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29053660

ABSTRACT

BACKGROUND: Non-surgical treatment has generally been recommended for stage II medication-related osteonecrosis of the jaw (MRONJ) in preference to surgery. However, non-surgical treatment is not empirically effective. The aim of this study was to evaluate whether surgical or non-surgical treatment leads to better outcomes for stage II MRONJ. MATERIAL AND METHODS: In this retrospective study, surgery was performed in a total of 28 patients while 24 patients underwent non-surgical treatment. The outcomes of both treatment approaches after 6 months were evaluated and statistically compared. In addition, risk factors for surgical and non-surgical treatments were assessed for each. RESULTS: Surgical treatment in 25 patients (89.3%) resulted in success, with failure in 3 patients (10.7%). Non-surgical treatment was successful for 8 patients (33.3%) and failed in 16 patients (66.7%). There was therefore a significant difference between surgical and non-surgical treatment outcomes (P<0.01). Regarding risk factors, in non-surgical treatment primary diseases, medications, and drug holiday had a significant effect on outcomes (P<0.01). Risk factors for surgical treatment could not be clarified. CONCLUSIONS: Surgical treatment is more effective than non-surgical treatment for stage II MRONJ, and drug holiday, primary disease, and medication constitute risk factors in non-surgical treatment.


Subject(s)
Jaw Diseases/chemically induced , Jaw Diseases/therapy , Osteonecrosis/chemically induced , Osteonecrosis/therapy , Aged , Aged, 80 and over , Female , Humans , Jaw Diseases/surgery , Male , Osteonecrosis/surgery , Retrospective Studies , Risk Factors , Treatment Outcome
2.
J Dairy Sci ; 97(11): 7151-61, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25242424

ABSTRACT

The objective of this experiment was to measure ruminal and lactational responses of Holstein dairy cows fed diets containing 3 different starch levels: 17.7 (low; LS), 21.0 (medium; MS), or 24.6% (high; HS). Twelve multiparous cows (118 ± 5 d in milk) were assigned randomly to dietary treatment sequence in a replicated 3 × 3 Latin square design with 3-wk periods. All diets were fed as total mixed rations and contained approximately 30.2% corn silage, 18.5% grass silage, and 5.0% chopped alfalfa hay. Dietary starch content was manipulated by increasing dry ground corn inclusion (% of dry matter) from 3.4 (LS) to 10.1 (MS) and 16.9 (HS) and decreasing inclusion of beet pulp and wheat middlings from 6.7 and 13.4 (LS) to 3.4 and 10.1 (MS) or 0 and 6.8 (HS). In vitro 6-h starch digestibility of the diet increased as nonforage sources of fiber replaced corn grain (% of dry matter; 73.6, HS; 77.3, MS; 82.5, LS) resulting in rumen-fermentable starch content by 14.6, 16.2, and 18.1% for the LS, MS, and HS diets, respectively. Diets had similar neutral detergent fiber from forage and particle size distributions. Dry matter intake, solids-corrected milk yield, and efficiency of solids-corrected milk production were unaffected by diet, averaging 26.5 ± 0.8, 40.8 ± 1.6, and 1.54 ± 0.05 kg/d, respectively. Reducing dietary starch did not affect chewing time (815 ± 23 min/d), mean ruminal pH over 24h (6.06 ± 0.12), acetate-to-propionate ratio (2.4 ± 0.3), or microbial N synthesized in the rumen (585 ± 24 g/d). Total tract organic matter digestibility was higher for HS compared with MS and LS diets (69.2, 67.3, and 67.0%, respectively), but crude protein, neutral detergent fiber, and starch digestibilities were unaffected. As dietary starch content decreased, in vitro ruminal starch fermentability increased and, consequently, the range between HS and LS in rumen-fermentable starch (3.5 percentage units) was less than the range in starch content (6.9 percentage units). Under these conditions, dietary starch content had no measurable effect on ruminal fermentation or short-term lactational performance of high-producing Holstein dairy cows.


Subject(s)
Animal Feed/analysis , Cattle/physiology , Dietary Carbohydrates/analysis , Milk , Silage , Starch/chemistry , Animal Nutritional Physiological Phenomena , Animals , Diet/veterinary , Dietary Fiber , Digestion/physiology , Female , Fermentation , Lactation/physiology , Milk/metabolism , Rumen/metabolism , Starch/metabolism , Zea mays/metabolism
3.
Int J Oral Maxillofac Surg ; 52(5): 539-542, 2023 May.
Article in English | MEDLINE | ID: mdl-36243644

ABSTRACT

Although the pectoralis major myocutaneous (PMMC) flap is among the useful reconstructive materials following oral cancer ablation, this flap has an unstable blood circulation that could result in partial necrosis of the skin paddle. This report describes the usefulness of indocyanine green angiography (ICGA) to achieve complete engraftment of the PMMC flap. Five patients with oral cancer underwent reconstruction with a PMMC flap after cancer ablation. During the skin paddle design and flap elevation, the blood supply to the flap was assessed by ICGA. Areas of the skin paddle that showed no ICG fluorescence were excised. Consequently, prior to transfer to the recipient site, the blood supply to all flaps was confirmed with indocyanine green visible at the edge of the skin paddle, and complete engraftment was achieved without partial necrosis. Based on the results observed, ICGA would make a useful contribution to complete engraftment of the PMMC flap.


Subject(s)
Mouth Neoplasms , Myocutaneous Flap , Plastic Surgery Procedures , Humans , Indocyanine Green , Pectoralis Muscles/blood supply , Pectoralis Muscles/transplantation , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/surgery , Angiography , Necrosis
4.
Scand J Immunol ; 75(1): 120-6, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21923741

ABSTRACT

Neutropenia associated with Kawasaki Syndrome (KS) has been rarely reported, and the detailed mechanisms responsible for this state are not yet elucidated. The aim of this study was to clarify the mechanisms of neutropenia in KS. We examined antibodies to known neutrophil antigens (HNA1a, HNA1b, HNA null, HNA2, HNA3, HNA4 and non-HLA antigen 9a) in a KS patient with neutropenia. We also performed the granulocyte immunofluorescence test (GIFT) using patient or control neutrophils incubated with the patient's serum at serial time points over the patient's clinical course. No specific antibody to known neutrophil antigens was detected. Flow cytometric analysis showed that autoantibodies bound to immature CD13-positive myeloid cells, which resulted in myeloid lineage maturation arrest in the bone marrow. GIFT showed that neutrophil-specific autoantibodies were produced by the patient, and the amount of autoantibody inversely correlated with the patient's neutrophil counts. The presence of an autoantibody to a novel antigen on immature myeloid cells or neutrophils is the likely the cause of severe neutropenia in this patient with KS.


Subject(s)
Autoantibodies/immunology , Mucocutaneous Lymph Node Syndrome/immunology , Neutropenia/immunology , Autoantibodies/blood , Bone Marrow/immunology , Child, Preschool , Flow Cytometry , Humans , Hydrocortisone/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Male , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/drug therapy , Neutropenia/blood , Neutropenia/drug therapy
5.
J Phys Chem B ; 113(26): 8847-53, 2009 Jul 02.
Article in English | MEDLINE | ID: mdl-19552455

ABSTRACT

We measured the surface tension of aqueous solutions of octanol-butandiyl-1,4-bis(decyldimethylammonium bromide) using the drop-volume technique at 298.15 K under atmospheric pressure as a function of the total molality and bulk composition. The results of the surface tension measurements, which were analyzed by originally developed thermodynamic equations, suggested that octanol molecules filled the spaces among the hydrophobic chains of gemini surfactants and formed a densely packed monolayer with them in the adsorbed film. The turbidity of aqueous solutions was also measured to construct the concentration-composition diagram with the surface tension data. A transmission electron microscope was used to determine the aggregate morphology in the aqueous solutions. Disc-like micelle and microemulsion regions were found on the diagram prior to the spherical micelle formation; nevertheless, the butandiyl-1,4-bis(decyldimethylammonium bromide) itself formed only spherical (or small ellipsoid) micelles in the concentration range measured. We also studied the relationship between synergism and molecular packing in the aggregates.

6.
Oncogene ; 26(4): 509-20, 2007 Jan 25.
Article in English | MEDLINE | ID: mdl-16862181

ABSTRACT

As alterations in retinoblastoma (RB)/E2F pathway are commonly found in human cancers, the molecular mechanism underlying cell cycle deregulation caused by the mutations in the RB/E2F pathway needs to be investigated extensively. Compared with good understanding of RB/E2F functions in G1-S cell cycle progression, it is not fully understood how an abrogated RB pathway affects the G2-M phase of the cell cycle. Here, we report that disruption of RB accelerated G2-M progression in the presence of DNA damage by elevating the expression of a set of mitotic regulatory genes. We generated RB(+)- and (-)-matched cells using short hairpin RNA. In the RB(-) cells, the G2/M checkpoint mediated by a DNA-damaging agent was over-ridden. With microarray analysis, we found that the expression of key G2-M regulatory genes was upregulated in RB(-) cells. In particular, we demonstrated that the proto-oncogene ECT2 was directly regulated by E2Fs. Furthermore, suppression of ECT2 expression by small interfering RNA in RB(-) cells resulted in cytokinesis arrest, suggesting that RB(-) cells lack the regulation of E2F-mediated cytokinesis. These results indicate that aberrant ECT2 expression, observed in various human tumors, could be the direct result of RB/E2F pathway deficiency, thereby contributing to cell division in cancers.


Subject(s)
Cell Division , DNA Damage , G2 Phase , Proto-Oncogene Proteins/metabolism , Retinoblastoma Protein/antagonists & inhibitors , Cell Line , Cell Proliferation , E2F Transcription Factors/metabolism , Gene Expression Regulation , HeLa Cells , Humans , Promoter Regions, Genetic , Proto-Oncogene Mas , Proto-Oncogene Proteins/genetics , RNA Interference
7.
J Dent Res ; 87(4): 396-400, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18362327

ABSTRACT

Orthodontic force induces osteoclastogenesis in vivo. It has recently been reported that administration of an antibody against the macrophage-colony-stimulating factor (M-CSF) receptor c-Fms blocks osteoclastogenesis and bone erosion induced by tumor necrosis factor-alpha (TNF-alpha) administration. This study aimed to examine the effect of an anti-c-Fms antibody on mechanical loading-induced osteoclastogenesis and osteolysis in an orthodontic tooth movement model in mice. Using TNF receptor 1- and 2-deficient mice, we showed that orthodontic tooth movement was mediated by TNF-alpha. We injected anti-c-Fms antibody daily into a local site, for 12 days, during mechanical loading. The anti-c-Fms antibody significantly inhibited orthodontic tooth movement, markedly reduced the number of osteoclasts in vivo, and inhibited TNF-alpha-induced osteoclastogenesis in vitro. These findings suggest that M-CSF plays an important role in mechanical loading-induced osteoclastogenesis and bone resorption during orthodontic tooth movement mediated by TNF-alpha.


Subject(s)
Antibodies, Monoclonal/pharmacology , Immunoglobulin G/pharmacology , Receptor, Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Tooth Movement Techniques , Acid Phosphatase/antagonists & inhibitors , Animals , Biomarkers/analysis , Bone Resorption/physiopathology , Cell Differentiation/drug effects , Isoenzymes/antagonists & inhibitors , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Models, Animal , Osteoclasts/drug effects , Osteolysis/physiopathology , Receptors, Tumor Necrosis Factor, Type I/antagonists & inhibitors , Receptors, Tumor Necrosis Factor, Type II/antagonists & inhibitors , Stress, Mechanical , Tartrate-Resistant Acid Phosphatase , Tumor Necrosis Factor-alpha/antagonists & inhibitors
8.
J Hum Hypertens ; 22(2): 144-6, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17728800

ABSTRACT

Pulse wave analysis was performed in apparently normal volunteers (n=164) and in essentially hypertensive patients without cardiovascular complications (n=171) using a newly developed non-invasive pulse wave measurement device (HEM-9010AI). Our results suggest that early wave reflections measured by radial augmentation index (AIr) are enhanced in volunteers with systolic blood pressure (SBP) >or= 160 mm Hg compared with the volunteers with their SBP<160 mmHg (98+/-18 vs 88+/-12, P<0.05). Furthermore, AIr is lower in hypertensive patients with long-term antihypertensive treatment than in those with short-term treatment (84+/-10 vs 89+/-13, P<0.01).


Subject(s)
Arteries/physiology , Hypertension/drug therapy , Aged , Blood Pressure/physiology , Elasticity , Female , Humans , Male , Middle Aged , Pulse , Time Factors
9.
J Phys Condens Matter ; 20(27): 275225, 2008 Jul 09.
Article in English | MEDLINE | ID: mdl-21694386

ABSTRACT

Time-dependent Ginzburg-Landau (TDGL) formulation has been developed for the ordering processes of B2 and D0(3) types in binary alloy systems. In the formulation, three order parameters are defined in order to describe the state of order. Equivalent variants of B2 and D0(3) structures are distinguished using these order parameters. The mean-field free energy is defined in the form of a Landau-type expansion using the order parameters and a composition parameter. Interface energies due to local variations in the degrees of order and concentration are given with a gradient square approximation. Kinetic equations are derived from the Ginzburg-Landau-type potential in order to describe the time-evolutions of the order parameters and the concentration. Numerical simulations of the kinetic equations have been performed for B2- and D0(3)-type ordering as well as concurrent ordering and phase separation to disordered A2+D0(3). The simulated results provide a good reproduction of the formation processes of B2 and D0(3) ordered domains in an Fe(3)Al alloy.

10.
Anticancer Res ; 27(4C): 2673-7, 2007.
Article in English | MEDLINE | ID: mdl-17695431

ABSTRACT

UNLABELLED: The aim of this study was to determine the recommended dose of irinotecan in combination with the fixed dose of oral UFT as first-line therapy in patients with advanced or recurrent colorectal cancer, and to evaluate the response rate and overall survival as a phase II study. PATIENTS AND METHODS: Thirteen patients were recruited into a phase I trial. Four doses of irinotecan ranging from 60 to 150 mg/m2/day were administered intravenously on day 1 and day 16 in combination with UFT given orally from day 2 to day 15. In a phase II study, 53 patients received at least one cycle of this therapy. RESULTS: The recommended dose of this combination was determined as irinotecan 120 mg/m2/day and UFT 400 mg/m2/day. Dose-limiting toxicities were neutropenia and prolonged leucopenia. On an intent-to-treat analysis, the response rate in the phase II study was 24.5% (95% confidence interval 13.8% to 38.2%). The median overall survival time was 20.3 months (95% confidence interval, 15.0-22.8 months). Out of 20 patients with stable disease, 17 who received more than 4 cycles of the regimen lived longer than the other 3 patients who received fewer than 3 cycles (p = 0.0353). Hematological adverse events were mainly grade 3/4 neutropenia observed in 6 out of 53 patients. Grade 3 non-hematological toxicities, such as diarrhea, anorexia, nausea/vomiting and alopecia were observed in 6 patients. CONCLUSION: Irinotecan combined with oral UFT was effective and well-tolerated. This regimen may be considered as a first-line therapy for advanced or metastatic colorectal cancer and may result in fairly long survival, even for patients with stable disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Colorectal Neoplasms/pathology , Drug Administration Schedule , Female , Humans , Irinotecan , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Tegafur/administration & dosage , Tegafur/adverse effects , Uracil/administration & dosage , Uracil/adverse effects
11.
J Exp Clin Cancer Res ; 26(2): 241-51, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17725105

ABSTRACT

IFL [irinotecan (CPT-11), 5-fluorouracil (5-FU), and folinic acid] is one of the treatments for metastatic colorectal cancer. We evaluated cytotoxic effects of a sequentially administered a combination of 5-FU with CPT-11 in human p53 mutant colon cancer. Sequential combination of 5-FU and CPT-11 in human colon cancer SW480 cells using a WST-8 colorimetric assay was studied. Cytotoxicity and cell cycle distribution for each drug were evaluated using an apoptosis assay and flow cytometry. Potential mechanisms of sequence-dependent cytotoxic effects were investigated using microarrays. Cytotoxicity of 5-FU (10, 100, 1000 microM) combined with subsequent use of CPT-11 (1 microM) was significantly greater than the reverse sequence of CPT-11 followed by 5-FU (p < 0.05). Following 24 hrs treatment with 5-FU (0.1-100 microM), no significant apoptosis was observed. In contrast, apoptosis was significantly induced after 24 hrs treatment with CPT-11 (1 and 10 microM). Flow cytometric analysis showed no significant difference in cell cycle distribution between different drug concentrations. We demonstrated up-regulation of 85 genes and down-regulation of 21 genes correlating with sequence-dependent cytotoxicities of 5-FU and CPT-11. The superiority of 5-FU-CPT-11 sequence was proven for p53 mutant colon cancer, SW480. Treatment with 5-FU followed by CPT-11 administration may be the optimal sequence for IFL treatment of metastatic colon cancers.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Fluorouracil/administration & dosage , Apoptosis , Camptothecin/administration & dosage , Camptothecin/therapeutic use , Drug Administration Schedule , Fluorouracil/therapeutic use , Gene Expression , Gene Expression Profiling , Humans , Irinotecan , Leucovorin/therapeutic use , Mutation , Oligonucleotide Array Sequence Analysis , Tumor Cells, Cultured , Up-Regulation
12.
Int J Oral Maxillofac Surg ; 35(7): 594-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16697142

ABSTRACT

A 2-stage procedure combining maxillary advancement by distraction technique with mandibular setback surgery was used to correct jaw deformities in 5 patients with severe maxillary retrusion secondary to cleft lip and palate. First, a Le Fort I maxillary osteotomy was performed. Immediately after maxillary distraction, the distraction device was removed. The advanced maxilla was fixed with miniplates after adjusting the length and direction of advancement, and mandibular setback surgery was performed simultaneously to obtain a normal occlusal relationship. This 2-stage procedure resulted in stable occlusion and a markedly improved facial profile.


Subject(s)
Cleft Palate/complications , Malocclusion, Angle Class III/surgery , Oral Surgical Procedures/methods , Orthognathic Surgical Procedures , Osteogenesis, Distraction , Prognathism/surgery , Retrognathia/surgery , Adolescent , Adult , Cephalometry , Cleft Lip/complications , Humans , Jaw Fixation Techniques/instrumentation , Male , Malocclusion, Angle Class III/etiology , Osteogenesis, Distraction/instrumentation , Osteotomy, Le Fort , Prognathism/complications , Retrognathia/complications
13.
Oncogene ; 19(41): 4773-86, 2000 Sep 28.
Article in English | MEDLINE | ID: mdl-11032028

ABSTRACT

The repressive effect of the 3'-untranslated region (3'-UTR) in human connective tissue growth factor/ hypertrophic chondrocyte specific 24 (ctgf/hcs24) mRNA on gene expression had been demonstrated in our previous study. Here, we identified a minimal RNA element in the 3'-UTR, which acts as a cis-acting element of structure-anchored repression (CAESAR). Deletion analyses of the 3'-UTR led us to minimize the element of 84 bases at the junction of the coding region and the 3'-UTR. The minimized RNA segment is predicted, and actually capable of forming a stable secondary structure in vitro. Mutational analyses disclosed a significant relationship between the predicted structure and repressive effect. The utility of CAESAR as a post-transcriptional regulatory element was represented by the fact that steady-state mRNA levels were not affected by CAESAR linked in cis, while protein levels from such a chimeric gene were markedly reduced. Of note, the CAESAR sequence exerted no effect, when it was placed upstream of the promoter. Finally, RNA gel electromobility-shift analyses demonstrated a nuclear factor that interacts with the folded CAESAR. Taken together, it was uncovered that CAESAR of ctgf is a novel post-transcriptional structured RNA regulatory element, probably acting through direct interactions with a nuclear factor as observed in retroviral RNA elements with certain proteins.


Subject(s)
3' Untranslated Regions/physiology , Gene Expression Regulation , Growth Substances/genetics , Immediate-Early Proteins/genetics , Intercellular Signaling Peptides and Proteins , RNA Processing, Post-Transcriptional , RNA, Messenger/genetics , Regulatory Sequences, Nucleic Acid , 3' Untranslated Regions/chemistry , 3T3 Cells , Animals , Base Pairing , Base Sequence , COS Cells , Chlorocebus aethiops , Connective Tissue Growth Factor , Genes, Reporter , Genes, Synthetic , Growth Substances/biosynthesis , HeLa Cells , Humans , Immediate-Early Proteins/biosynthesis , Mice , Molecular Sequence Data , Nucleic Acid Conformation , Sequence Deletion , Structure-Activity Relationship
14.
Biochim Biophys Acta ; 1357(3): 306-18, 1997 Jul 24.
Article in English | MEDLINE | ID: mdl-9268055

ABSTRACT

The perfusion of rat small intestine with 10 microM epinephrine (Epi) or 10 microM norepinephrine resulted in significant increases in the amount of 3-O-[methyl-3H]-D-glucose transported from the mucosal to serosal side. The Epi-induced increases in glucose transport were coupled with selective increases in beta-adrenoceptor density in the mucosal membranes. Treatment with 0.1 microM okadaic acid increased glucose transport even in the absence of Epi, but that with 1 microM staurosporine or 60 microM N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide dihydrochloride completely inhibited the increases in glucose transport induced by 10 microM Epi or 10 microM dibutyryl cAMP. The maximal binding sites (Bmax) of [3H]phlorizin in brush border membrane (BBM) from tissues perfused with Epi was increased, showing increases in the binding ability of the Na+/glucose cotransporter (SGLT1) to glucose. Phosphorylation and dephosphorylation of BBM with protein kinase A (PKA) and alkaline phosphatase resulted in increases and decreases in Bmax of [3H]phlorizin, respectively. The phosphorylation state of SGLT1 immunoprecipitated from BBM incubated with [gamma-32P]ATP-Mg2+ and PKA, and the analysis of phosphoamino acids composed of SGLT1 in rats given [32P]orthophosphate indicate the presence of potential sites for PKA-mediated phosphorylation of SGLT1 at serine. These findings indicate that the regulation of phosphorylation of SGLT1 leads to an alteration of its function and results in the control of glucose transport in the rat small intestine.


Subject(s)
Adrenergic beta-Agonists/pharmacology , Glucose/metabolism , Intestine, Small/metabolism , Membrane Glycoproteins/physiology , Monosaccharide Transport Proteins/physiology , Animals , Biological Transport , Epinephrine/pharmacology , In Vitro Techniques , Male , Norepinephrine/pharmacology , Okadaic Acid/pharmacology , Ouabain/pharmacology , Phlorhizin/pharmacology , Phosphorylation , Rats , Rats, Wistar , Sodium-Glucose Transporter 1 , Staurosporine/pharmacology , Vinblastine/pharmacology
15.
Biochim Biophys Acta ; 1265(2-3): 173-80, 1995 Mar 16.
Article in English | MEDLINE | ID: mdl-7696346

ABSTRACT

Short-term treatment of rat submandibular tissues with 10 microM isoproterenol (IPR) resulted in reduction of mucin secretion in response to the agonist during further incubation, and in increases in EC50 values. This IPR-induced reduction of secretion was coupled with selective decreases in the number of beta-adrenoceptors in the tissues and in their affinity for agonists, as assessed by measurement of the specific binding of [3H]dihydroalprenolol. Treatment of the tissues with IPR caused a 30% decrease in IPR-stimulated adenylate cyclase activity and a 25% increase in the GTP binding capacity of inhibitory G proteins (Gi proteins). This IPR treatment triggered a 60% increase in the ability of pertussis toxin (IAP) to catalyze ADP-ribosylation of Gi proteins in the tissue membranes. Enhanced function of stimulatory G proteins (Gs proteins) was observed only during the first incubation of the tissues with IPR. The IAP-catalyzed ADP-ribosylation of Gi proteins in tissues treated with IPR was decreased by prior treatment with cyclic AMP dependent protein kinase, but was increased markedly by prior treatment with alkaline phosphatase. Neither IPR-induced desensitization of protein secretion nor increase in the IAP-catalyzed ADP-ribosylation of Gi proteins was observed in the tissues pretreated with 0.25 microM okadaic acid. These findings suggest that the regulation of Gi protein phosphorylation plays an important role in the IPR-induced heterologous desensitization of mucin secretion from rat submandibular glands.


Subject(s)
GTP-Binding Proteins/metabolism , Isoproterenol/pharmacology , Mucins/metabolism , Submandibular Gland/metabolism , Adrenergic beta-Agonists/pharmacology , Animals , In Vitro Techniques , Male , Radioligand Assay , Rats , Rats, Wistar , Second Messenger Systems , Signal Transduction
16.
Biochim Biophys Acta ; 1313(2): 146-56, 1996 Aug 28.
Article in English | MEDLINE | ID: mdl-8781562

ABSTRACT

Treatment of rat parotid tissues with 1 microM isoproterenol (IPR) for 10 min caused a 60% decrease in pertussis toxin (IAP)-catalyzed ADP-ribosylation of Gi alpha and resulted in supersensitivity of amylase secretion from the tissues. However, conversely, IPR treatment for 30 min caused a 40% increase in IAP-catalyzed ADP-ribosylation of Gi alpha, coupled with desensitization of amylase secretion. No changes in Gs function were observed in IPR-induced phenomena. Pretreatment with okadaic acid induced enhancement of the supersensitivity of amylase secretion and disappearance of the desensitization. These phenomena were accompanied with decreases in IAP-catalyzed ADP-ribosylation of Gi alpha. IPR treatment for 30 min caused a 50% decrease in phosphorylation of Gi2 alpha immunoprecipitated with anti-G protein antiserum (AS/7) from [32P]Pi-labeled cells, but such treatment for 10 min caused a 40% increase in phosphorylation in the cells pretreated with okadaic acid. Phosphorylation and dephosphorylation of immunoprecipitates with AS/7 by protein kinase A (PKA) and alkaline phosphatase caused decreases and increases in IAP-catalyzed ADP-ribosylation, respectively, indicating the presence of PKA-mediated phosphorylation sites on Gi2 alpha. Thus, the control of the phosphorylation of Gi2 alpha is of importance and relevance in the regulation of biological processes and cellular responses.


Subject(s)
Amylases/metabolism , GTP-Binding Proteins/physiology , Isoproterenol/pharmacology , Parotid Gland/metabolism , Adenosine Diphosphate Ribose/metabolism , Animals , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/physiology , Down-Regulation/drug effects , Enzyme Inhibitors/pharmacology , Ethers, Cyclic/pharmacology , Guanosine 5'-O-(3-Thiotriphosphate)/metabolism , Male , Okadaic Acid , Phosphoprotein Phosphatases/antagonists & inhibitors , Phosphoprotein Phosphatases/physiology , Phosphorylation , Rats , Rats, Wistar , Receptors, Adrenergic, beta/physiology , Secretory Rate/drug effects , Signal Transduction , Up-Regulation/drug effects
17.
Biochim Biophys Acta ; 1390(3): 339-45, 1998 Feb 23.
Article in English | MEDLINE | ID: mdl-9487155

ABSTRACT

A new ether lipid core (designated as FU) was found in Methanothermus fervidus total lipid. Comparison with caldarchaeol showed lower mobility of FU on TLC and smaller molecular weight (m/z 1298) by 2 mass units on FAB-MS. Treatment of FU with HI followed by displacement with silver acetate afforded long chain alcohol acetate (ROAc), which was further saponified with mild alkali to its free alcohol (ROH). ROH is the long chain alcohol prepared from FU. The molecular weights of ROAc and ROH were shown by MS to be 1354 and 1186, respectively. These results suggested that the molecular formula of ROH was C80H162O4, and ROH had four hydroxyl groups, and one molecule of ROH was bound with two molecules of glycerol by four ether linkages. Because FU was not oxidized by NaIO4 and specific rotation [alpha]D of FU coincided with that of caldarchaeol, it seems that the ether linkages of FU are formed with hydroxyl groups of the sn-2 and sn-3 positions of each glycerol moiety. The structure of FU was suggested to be a modified caldarchaeol in which two hydrocarbon chains are bridged with a covalent bond. Although a few points remain to be elucidated before the final conclusion can be reached on the structure of FU due to difficulty in complete structure determination done even with every approach currently available, the most possible position of the bridge in FU hydrocarbon was proposed from the data of EI-MS of ROAc and 1H-NMR of FU. The hydrocarbon chain looks like H-shaped C80 isoprenoid.


Subject(s)
Euryarchaeota/chemistry , Lipids/isolation & purification , Ether/chemistry , Glycerol/chemistry , Glyceryl Ethers/chemistry , Lipids/chemistry , Molecular Weight , Terpenes/chemistry
18.
Clin Cancer Res ; 6(7): 2707-11, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10914714

ABSTRACT

Thymidylate synthase (TS) is thought to be one of the target genes that the E2F1 transcription factor binds to and regulates. However, the relationship between the expressions of TS and E2F1 in primary colon cancer specimens remains unclear. The aim of this study was to define the relation of TS and E2F1 gene expressions in tumor samples from 23 colon cancer patients. TS and E2F1 gene expressions were measured by TaqMan reverse transcription-PCR assay using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard and expressed as a TS:GAPDH or E2F1:GAPDH mRNA ratio. A close relationship was found between TS gene expression and E2F1 gene expression (r2 = 0.598, P < 0.001) in 23 tumor samples analyzed. Surprisingly, a high correlation between TS gene expression and E2F1 gene expression was observed even in advanced tumors from stage IV colon cancer patients. These results suggest that transcription of the TS gene may be regulated by E2F1 in primary colon cancer specimens and that this gene-regulatory pathway from E2F1 to TS may be highly conserved during malignant progression. Four of the 23 patients showed TS overexpression with increased E2F1 expression. These results suggest that the ability of a tumor to increase TS expression may possibly be due to an overexpression of E2F1. Although the number of patients was relatively small, our study provides new insights into the molecular mechanisms underlying the regulation of TS expression in colon cancers.


Subject(s)
Carrier Proteins , Cell Cycle Proteins , Colonic Neoplasms/genetics , DNA-Binding Proteins , Gene Expression Regulation, Neoplastic , Thymidylate Synthase/genetics , Transcription Factors/genetics , Adult , Aged , Aged, 80 and over , Calibration , Colonic Neoplasms/enzymology , Colonic Neoplasms/pathology , E2F Transcription Factors , E2F1 Transcription Factor , Female , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Humans , Male , Middle Aged , Neoplasm Staging , Polymerase Chain Reaction/methods , RNA, Neoplasm/genetics , Regression Analysis , Retinoblastoma-Binding Protein 1 , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factor DP1
19.
Vet Immunol Immunopathol ; 103(1-2): 113-27, 2005 Jan 10.
Article in English | MEDLINE | ID: mdl-15626467

ABSTRACT

A battery of mouse monoclonal antibodies (mAbs) reactive with porcine peripheral blood (PB) leukocytes was generated. Among the mAbs, 6F10 was found to react probably with cluster of differentiation (CD)8 alpha-chain, while 7G3 and 3E12 were found to recognize gammadelta T-cells, as revealed by two-color flow cytometric and immunoprecipitation studies. 7G3 was shown to react with the constant (C) region of the T-cell receptor (TCR) delta-chain by the following facts: (1) 7G3 immunoprecipitated full-length TCR delta-chain protein fused with glutathione S-transferase (GST) produced by Esherichia coli and (2) 7G3 reacted with TCR delta-chain expressing Cos-7 cells transfected with either full-length or N-terminal deleted mutant cDNA, but did not react with Cos-7 cells transfected with C-terminal deleted mutant TCR delta-chain cDNA. All three mAbs produced high-quality immunostaining results on frozen sections, revealing a distinct distribution of gammadelta T-cells and CD8(+) cells. This report precisely characterizes mAbs against porcine TCR for the first time, facilitating molecular biological investigations of the porcine immune system.


Subject(s)
Antibodies, Monoclonal/immunology , Lymphocytes/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , Swine/immunology , Amino Acid Sequence , Animals , Flow Cytometry , Immunohistochemistry , Immunoprecipitation , Molecular Sequence Data , Receptors, Antigen, T-Cell, gamma-delta/analysis , Receptors, Antigen, T-Cell, gamma-delta/genetics
20.
Oncogene ; 34(43): 5460-71, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25659585

ABSTRACT

Elevated levels of the inducible heat-shock protein 70 (Hsp72) have been implicated in mammary tumorigenesis in histological investigations of human breast cancer. We therefore examined the role of Hsp72 in mice, using animals in which the hsp70 gene was inactivated. We used a spontaneous tumor system with mice expressing the polyomavirus middle T (PyMT) oncogene under control of the mouse mammary tumor virus (MMTV) long-terminal repeat (MMT mice). These mice developed spontaneous, metastatic mammary cancer. We then showed Hsp72 to be upregulated in a fraction of mammary cancer initiating cells (CIC) within the MMT tumor cell population. These cells were characterized by elevated surface levels of stem cell markers CD44 and Sca1 and by rapid metastasis. Inactivation of the hsp70 gene delayed the initiation of mammary tumors. This delay in tumor initiation imposed by loss of hsp70 was correlated with a decreased pool of CIC. Interestingly, hsp70 knockout significantly reduced invasion and metastasis by mammary tumor cells and implicated its product Hsp72 in cell migration and formation of secondary neoplasms. Impaired tumorigenesis and metastasis in hsp70-knockout MMT mice was associated with downregulation of the met gene and reduced activition of the oncogenic c-Met protein. These experiments therefore showed Hsp72 to be involved in the growth and progression of mammary carcinoma and highlighted this protein as a potential target for anticancer drug development.


Subject(s)
Cell Transformation, Neoplastic/genetics , HSP72 Heat-Shock Proteins/genetics , Neoplasm Metastasis/genetics , Animals , Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Cell Movement/genetics , Cell Transformation, Neoplastic/drug effects , Down-Regulation/drug effects , Down-Regulation/genetics , Female , Mammary Neoplasms, Experimental/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Neoplasm Metastasis/drug therapy , Oncogenes/genetics , Proto-Oncogene Proteins c-met/genetics
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