Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 14 de 14
Filter
Add more filters











Publication year range
1.
Viruses ; 15(8)2023 07 30.
Article in English | MEDLINE | ID: mdl-37632005

ABSTRACT

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen-antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6-8 months regardless of the subsequent change in the antibody levels.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Antibodies, Viral
2.
Influenza Other Respir Viruses ; 17(3): e13119, 2023 03.
Article in English | MEDLINE | ID: mdl-36909295

ABSTRACT

Background: There is a need for vaccines that can induce effective systemic, respiratory mucosal, and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA, and cellular immunity. Methods: The aim of the present study was to determine the effectiveness of a new administration route of trans-airway (TA) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local, and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AddaS03™ (S1-AddaS03™ vaccine). Results: S1-SF-10-TA vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-TA showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AddaS03™-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AddaS03™-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF-10-TA, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusions: Based on the need for effective systemic, respiratory, and cellular immunity, the S1-SF-10-TA vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.


Subject(s)
COVID-19 , Pulmonary Surfactants , Humans , Animals , Mice , Pulmonary Surfactants/pharmacology , SARS-CoV-2 , Interleukin-4/pharmacology , Pandemics , Immunity, Mucosal , Antibodies, Viral , Adjuvants, Immunologic , Immunity, Cellular , Immunoglobulin A/pharmacology , Immunoglobulin G
3.
Nutrients ; 15(3)2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36771462

ABSTRACT

Food allergy is one of the major existing health problems, but no effective treatment is available. In the current work, a murine model that closely mimics pathogenesis of human food allergy and its quantifiable diagnostic parameter design, even for mild hypersensitivity reactions, were established. BALB/c mice were epicutaneously sensitized with 1 mg chicken egg ovomucoid (OVM) or cow's milk casein, free of adjuvants, five times a week for two consecutive weeks. Eleven days later, allergen-specific IgG1 and IgE in serum were measured by ELISA. On day 25, 20 mg OVM or 12 mg α-casein was administered orally, and allergic reactions such as the fall in rectal temperature, symptom scores during 90-120 min, serum mast cell protease-1 and cytokine levels were monitored. The detection of mild allergic reactions due to adjuvant-free allergen sensitization and oral allergen challenge routes was amplified by the combination of oral allergen and aspirin administration simultaneously or aspirin administration within 15-30 min before an allergen challenge. Quantification of the maximum symptom score and the frequency of symptoms during the monitoring period improved evaluation accuracy of food allergy signals. Based on these results, efficacy of casein oral immunotherapy for cow's milk allergies, which are generally difficult to detect, was monitored adequately.


Subject(s)
Food Hypersensitivity , Milk Hypersensitivity , Humans , Female , Cattle , Mice , Animals , Allergens , Caseins , Aspirin , Disease Models, Animal , Food Hypersensitivity/diagnosis , Food Hypersensitivity/therapy , Milk Hypersensitivity/diagnosis , Milk Hypersensitivity/therapy , Adjuvants, Immunologic , Ovomucin , Immunotherapy
4.
Vaccine ; 37(4): 612-622, 2019 01 21.
Article in English | MEDLINE | ID: mdl-30553569

ABSTRACT

We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC II+CD11c+ cells and their CD11b+CD103+ and CD11b+CD103- subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10. Oral vaccination with influenza hemagglutinin vaccine (HAv)-SF-10 induced HAv-specific IgA and IgG in the serum, and HAv-specific secretory IgA and IgG in bronchoalveolar lavage fluid, nasal washes, gastric extracts and fecal material; their levels were significantly higher than those induced by subcutaneous HAv or intranasal HAv and HAv-SF-10 vaccinations. Enzyme-linked immunospot assay showed high numbers of HAv-specific IgA and IgG antibody secreting cells in the gastrointestinal and respiratory mucosal lymphoid tissues after oral vaccination with HAv-SF-10, but no or very low induction following oral vaccination with HAv alone. Oral vaccination with HAv-SF-10 provided protective immunity against severe influenza A virus infection, which was significantly higher than that induced by HAv combined with cholera toxin. Oral vaccination with HAv-SF-10 was associated with unique cytokine production patterns in the spleen after HAv stimulation; including marked induction of HAv-responsive Th17 cytokines (e.g., IL-17A and IL-22), high induction of Th1 cytokines (e.g., IL-2 and IFN-γ) and moderate induction of Th2 cytokines (e.g., IL-4 and IL-5). These results indicate that oral vaccination with HAv-SF-10 induces more efficient systemic and local immunity than nasal or subcutaneous vaccination with characteristically high levels of secretory HAv-specific IgA in various mucosal organs and protective immunity.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Hemagglutinin Glycoproteins, Influenza Virus/administration & dosage , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Immunity, Mucosal , Orthomyxoviridae Infections/prevention & control , Pulmonary Surfactants/administration & dosage , Pulmonary Surfactants/immunology , Administration, Intranasal , Administration, Oral , Animals , Antibodies, Viral/blood , Cytokines/immunology , Female , Humans , Injections, Subcutaneous , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/virology , Pulmonary Surfactants/chemistry , Th1 Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Vaccination/methods
5.
Article in English | MEDLINE | ID: mdl-29406285

ABSTRACT

The influenza A virus (IAV)-cytokine-trypsin/matrix metalloproteinase-9 (MMP-9) cycle is one of the important mechanisms of multiple organ failure in severe influenza. Clarithromycin, a macrolide antibiotic, has immune modulatory and anti-inflammatory effects. We analyzed the effects of clarithromycin on the induction of chemokines, cytokines, MMP-9, trypsin, vascular hyper-permeability and inflammatory aggravation in mice with IAV infection. IAV/Puerto Rico/8/34(H1N1) infection increased the levels of monocyte chemoattractant protein-1 (MCP-1) and cytokines in serum, and MMP-9 and trypsin in serum and/or the lungs and heart. Clarithromycin significantly suppressed the induction of serum MCP-1 and MMP-9 and vascular hyperpermeability in these organs in the early phase of infection, but did not suppress the induction of trypsin, IL-6 or IFN-γ. Histopathological examination showed that clarithromycin tended to reduce inflammatory cell accumulation in the lungs and heart. These results suggest that clarithromycin suppresses infection-related inflammation and reduces vascular hyperpermeability by suppressing the induction of MCP-1 and MMP-9.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Chemokine CCL2/metabolism , Clarithromycin/therapeutic use , Influenza A virus , Lung/pathology , Matrix Metalloproteinase 9/metabolism , Myocardium/pathology , Orthomyxoviridae Infections/drug therapy , Animals , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology
6.
PLoS One ; 13(1): e0191133, 2018.
Article in English | MEDLINE | ID: mdl-29370185

ABSTRACT

We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity. Nasal instillation of ovalbumin, a model antigen, combined with SF-10 efficiently delivered antigen to mucosal dendritic and epithelial cells and promoted cross-presentation in antigen presenting cells, yielding a high percentage of ovalbumin-specific cytotoxic T lymphocytes in the nasal mucosa, compared with ovalbumin alone. Nasal immunization of HAv-SF-10 also induced HAv-specific cytotoxic T lymphocytes and upregulated granzyme B expression in splenic CD8+ T cells with their high cytotoxicity against target cells pulsed with HA peptide. Furthermore, nasal vaccination of HAv-SF-10 significantly induced higher cytotoxic T lymphocytes-mediated cytotoxicity in the lungs and cervical lymph nodes in the early phase of influenza virus infection compared with HAv alone. Protective immunity induced by HAv-SF-10 against lethal influenza virus infection was partially and predominantly suppressed after depletion of CD8+ and CD4+ T cells (induced by intraperitoneal injection of the corresponding antibodies), respectively, suggesting that CD4+ T cells predominantly and CD8+ T cells partially contribute to the protective immunity in the advanced stage of influenza virus infection. These results suggest that SF-10 promotes effective antigen delivery to antigen presenting cells, activates CD8+ T cells via cross-presentation, and induces cell-mediated immune responses against antigen.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Hemagglutination, Viral/immunology , Immunity, Cellular , Influenza Vaccines/administration & dosage , Molecular Mimicry , Pulmonary Surfactants/chemistry , Animals , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Influenza Vaccines/immunology , Lymphocyte Depletion , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nasal Mucosa/immunology
7.
Respir Investig ; 54(5): 312-9, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27566378

ABSTRACT

Severe influenza is characterized by cytokine storm and multiorgan failure. Influenza patients with underlying diseases show a rapid progression in disease severity. The major mechanism that underlies multiorgan failure during the progressive stage of infection, particularly in patients with underlying risk factors, is mitochondrial energy crisis. The relationship between the factors that determine infection severity, such as influenza virus, cytokines, cellular trypsin as a hemagglutinin processing protease for viral multiplication, accumulation of metabolic intermediates and ATP crisis in mitochondria, is termed the "influenza virus-cytokine-trypsin" cycle. This occurs during the initial stages of infection, and is interconnected with the "metabolic disorders-cytokine" cycle in the middle to late phase of infection. Experiments using animal models have highlighted the complex relationship between these two cycles. New treatment options have been proposed that target the ATP crisis and multiorgan failure during the late phase of infection, rather than antiviral treatments with neuraminidase inhibitors that work during the initial phase. These options are (i) restoration of glucose oxidation in mitochondria by diisopropylamine dichloroacetate, which inhibits infection-induced pyruvate dehydrogenase kinase 4 activity, and (ii) restoration of long-chain fatty acid oxidation in mitochondria by l-carnitine and bezafibrate, an agonist of peroxisome proliferation-activated receptors-ß/δ, which transcriptionally upregulates carnitine palmitoyltransferase II. The latter is particularly effective in patients with influenza-associated encephalopathy who have thermolabile and short half-life compound variants of carnitine palmitoyltransferase II.


Subject(s)
Influenza, Human/complications , Metabolic Diseases/complications , Animals , Energy Metabolism , Humans , Influenza A virus , Influenza, Human/therapy , Mice , Risk Factors
8.
Vaccine ; 34(16): 1881-8, 2016 Apr 07.
Article in English | MEDLINE | ID: mdl-26954466

ABSTRACT

Induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant SF-10 derived from pulmonary surfactant constituents. Split-product of influenza virus A/California/7/2009(H1N1)pdm hemagglutinin vaccine (HAv) at 15 µg with or without SF-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. SF-10-adjuvanted HAv (SF-10-HAv) elicited significantly higher HAv-specific IgG and hemagglutinin inhibition (HI) titers in serum and HAv-specific secretory IgA and its neutralizing activities in nasal washes compared with HAv antigen and SF-10 alone. Significant cross-neutralizing activities of nasal washes after the third vaccination to several other H1N1 and H3N2 strains were observed. HI titers in serum and neutralizing activities in nasal washes reached peak levels at 6 weeks after initial vaccination, then gradually decreased after 10 weeks and returned to the baseline levels at 36 weeks. A single intranasal revaccination of SF-10-HAv at 36 weeks rapidly and significantly increased both immunity in serum and nasal washes compared with naïve monkeys. Revaccination by one or two doses achieved almost maximal immunity at 2 or 4 weeks after instillation. Statistically significant adverse effects (e.g., body weight loss, elevated body temperature, nasal discharge, change in peripheral blood leukocyte and platelet counts) were not observed for 2 weeks after vaccination of SF-10-HAv, HAv or SF-10 and also during the experimental period. These results in young monkey model suggest the potential of clinical use SF-10 for intranasal flu vaccine.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Immunity, Mucosal , Immunologic Memory , Influenza Vaccines/immunology , Orthomyxoviridae Infections/prevention & control , Pulmonary Surfactants/immunology , Administration, Intranasal , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cross Protection , Hemagglutination Inhibition Tests , Immunoglobulin A, Secretory/immunology , Immunoglobulin G/blood , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H3N2 Subtype , Influenza Vaccines/administration & dosage , Macaca fascicularis , Male , Neutralization Tests , Vaccination/methods
9.
Proc Natl Acad Sci U S A ; 112(32): E4465-74, 2015 Aug 11.
Article in English | MEDLINE | ID: mdl-26224839

ABSTRACT

Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the molecular identities of pathogenic amyloid ß-protein (Aß) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10- to 15-nm spherical Aß oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na(+)/K(+)-ATPase α3 subunit (NAKα3). ASPD-binding to NAKα3 impaired NAKα3-specific activity, activated N-type voltage-gated calcium channels, and caused mitochondrial calcium dyshomeostasis, tau abnormalities, and neurodegeneration. NMR and molecular modeling studies suggested that spherical ASPD contain N-terminal-Aß-derived "thorns" responsible for target binding, which are distinct from low molecular-weight oligomers and dodecamers. The fourth extracellular loop (Ex4) region of NAKα3 encompassing Asn(879) and Trp(880) is essential for ASPD-NAKα3 interaction, because tetrapeptides mimicking this Ex4 region bound to the ASPD surface and blocked ASPD neurotoxicity. Our findings open up new possibilities for knowledge-based design of peptidomimetics that inhibit neurodegeneration in AD by blocking aberrant ASPD-NAKα3 interaction.


Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/toxicity , Sodium-Potassium-Exchanging ATPase/metabolism , Alzheimer Disease/pathology , Amino Acid Sequence , Animals , Calcium/metabolism , Cell Death/drug effects , Cells, Cultured , HEK293 Cells , Homeostasis/drug effects , Humans , Mass Spectrometry , Models, Biological , Models, Molecular , Molecular Imaging , Molecular Sequence Data , Molecular Weight , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Peptides/metabolism , Protein Aggregates , Protein Binding/drug effects , Rats , Signal Transduction/drug effects , Sodium/metabolism , Sodium-Potassium-Exchanging ATPase/chemistry
10.
Intern Med ; 52(21): 2447-51, 2013.
Article in English | MEDLINE | ID: mdl-24190150

ABSTRACT

A 62-year-old woman complained of repeated hypoglycemic events. A 75 g oral glucose tolerance test (75 gOGTT) showed a marked increase in the plasma insulin level and impaired glucose tolerance. The patient exhibited a high titer of plasma anti-insulin autoantibodies. Her diagnosis was insulin autoimmune syndrome (IAS). Following the cessation of loxoprofen-sodium (LOXs), she experienced no further hypoglycemic episodes. However, the hypoglycemic attacks recurred following the accidental readministration of LOXs in an adhesive skin patch. Considering the changes in the titer of anti-insulin autoantibodies, the repeated 75 gOGTT and the repeated Scatchard analysis, we determined LOXs to be the cause of the IAS and evaluated the characteristics of the autoantibodies.


Subject(s)
Autoimmune Diseases/etiology , Insulin Antibodies/blood , Phenylpropionates/adverse effects , Administration, Cutaneous , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/immunology , Autoantibodies/blood , Autoimmune Diseases/blood , Autoimmune Diseases/immunology , Blood Glucose/metabolism , Female , Humans , Hypoglycemia/blood , Hypoglycemia/etiology , Hypoglycemia/immunology , Insulin/blood , Insulin/immunology , Middle Aged , Phenylpropionates/administration & dosage , Phenylpropionates/immunology
11.
Influenza Other Respir Viruses ; 7(6): 1218-26, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23710832

ABSTRACT

BACKGROUND: We found previously that bovine pulmonary Surfacten® used in newborns with acute respiratory distress syndrome is a safe and efficacious antigen vehicle for intranasal vaccination. OBJECTIVES: The objective of this study was to industrially produce a synthetic adjuvant mimicking Surfacten® for clinical use without risk of bovine spongiform encephalopathy. METHODS: We selected three Surfacten lipids and surfactant protein (SP)-C as essential constituents for adjuvanticity. For replacement of the hydrophobic SP-C, we synthesized SP-related peptides and analyzed their adjuvanticity. We evaluated lyophilization to replace sonication for the binding of influenza virus hemagglutinin (HA) to the synthetic adjuvant. We also added a carboxy vinyl polymer (CVP) to the synthetic adjuvant and named the mixture as SF-10 adjuvant. HA combined with SF-10 was administered intranasally to mice, and induction of nasal-wash HA-specific secretory IgA (s-IgA) and serum IgG with Th1-/Th2-type cytokine responses in nasal cavity and virus challenge test were assessed. RESULTS AND CONCLUSIONS: Intranasal immunization with HA-SF-10 induced significantly higher levels of anti-HA-specific nasal-wash s-IgA and serum IgG than those induced by HA-poly(I:C), a reported potent mucosal vaccine, and provided highly efficient protection against lethal doses of virus challenge in mice. Anti-HA-specific serum IgG levels induced by HA-SF-10 were almost equivalent to those induced by subcutaneous immunization of HA twice. Intranasal administration of HA-SF-10 induced balanced anti-HA-specific IgG1 and IgG2a in sera and IFN-γ- and IL-4-producing lymphocytes in nasal cavity without any induction of anti-HA IgE. The results suggest that HA-SF-10 is a promising nasal influenza vaccine and that SF-10 can be supplied in large quantities commercially.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Influenza Vaccines/immunology , Vaccination/methods , Administration, Intranasal , Animals , Antibodies, Viral/analysis , Antibodies, Viral/blood , Blood/immunology , Cytokines/metabolism , Female , Immunoglobulin A/analysis , Immunoglobulin G/blood , Influenza Vaccines/administration & dosage , Mice , Mice, Inbred BALB C , Nasal Mucosa/immunology , T-Lymphocytes/immunology
12.
Endocr J ; 58(1): 65-8, 2011.
Article in English | MEDLINE | ID: mdl-21048358

ABSTRACT

Adult growth hormone deficiency (AGHD) is a recently recognized endocrine disorder characterized by low peak GH levels during provocative tests. The AGHD has a negative impact on bone mineral density, skeletal muscle strength, physical capacity and psychosocial well-being. Furthermore, the girls with GHD have delayed pubertal development, and in adulthood present a condition of subfertility. Treatment for AGHD with GH replacement therapy has been officially approved since 2006 in Japan. The patient was diagnosed as pituitary dwarfism at age 9. She was treated with GH replacement therapy since diagnosis until her height reached 155cm at age 15. When she was 24 years old, she suffered from clinical symptoms relating to GH deficiency, and she visited our hospital for reintroduction of the therapy to alleviate these clinical symptoms. She has been treated with the replacement therapy since then. The patient's dysmenorrhea improved. And she was found to be 8 weeks pregnant at age 28 years 7 months. We immediately ceased replacement therapy and carefully observed the patient, because it is not indicated for female patient with pregnancy. She delivered a healthy girl at 40 weeks of pregnancy, no recognizable side-effects were observed in either mother or baby. To our knowledge, there are no other reports of a Japanese patient becoming pregnant during GH replacement therapy, and few cases have been reported in other countries. It remains uncertain whether the therapy is safe and essential for fetal development, fertility, and continuation of pregnancy in AGHD subjects.


Subject(s)
Dwarfism, Pituitary/drug therapy , Growth Hormone/therapeutic use , Human Growth Hormone/deficiency , Pregnancy , Adult , Asian People , Child , Female , Human Growth Hormone/blood , Humans , Insulin-Like Growth Factor I/metabolism , Pregnancy/blood , Pregnancy Outcome
13.
Rinsho Ketsueki ; 48(7): 565-70, 2007 Jul.
Article in Japanese | MEDLINE | ID: mdl-17695306

ABSTRACT

A 63-year-old woman was diagnosed as having multiple myeloma (MM), IgG-kappa type, stage IIIA, in October 2003. She achieved partial response after receiving three courses of VAD therapy and one course of high dose dexamethasone therapy (HDD); maintenance therapy consisted of melphalan and prednisolone. In November 2004, the patient developed spinal canal stenosis that required surgery. At the end of December 2004, the patient developed renal dysfunction that progressed to anuria. A CT scan showed multiple retroperitoneal masses that impinged on and obstructed both ureters and caused bilateral hydronephroses. Renal function improved after a right percutaneous nephrostomy and chemotherapy consisting of HDD, cyclophosphamide, vincristine, and doxorubicin. Nevertheless, the patient died due to MM in February 2005. On autopsy, multiple retroperitoneal and pelvic plasmacytomas with 13q- and t(4;14) (p16;q32) were found. Our patient is a rare case that, in the terminal stage of MM, developed aggressive phase multiple myeloma with extramedullary plasmacytomas that caused acute renal failure due to compression on both ureters.


Subject(s)
Acute Kidney Injury/etiology , Multiple Myeloma/pathology , Plasmacytoma/pathology , Disease Progression , Female , Humans , Middle Aged , Multiple Myeloma/complications , Plasmacytoma/complications
14.
Hypertens Res ; 30(12): 1205-10, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18344626

ABSTRACT

Hypertension contributes to the occurrence and progression of cardiovascular diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to activate the peroxisome proliferator-activated receptor gamma and improve insulin sensitivity. We investigated the effects of telmisartan treatment on visceral fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive patients. This was an open-label, non-controlled study. Twenty-eight essential hypertensive patients (22 men and 6 women; age 60.6+/-1.9 years; body mass index [BMI] 25.5+/-0.6 kg/m(2)) participated. Fat area was assessed with computerized tomography. All the subjects were started on telmisartan 40 mg/day, which was increased to 80 mg/day to achieve the blood pressure target of less than 130/80 mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan treatment. There were significant reductions in visceral fat area (from 103.1+/-7.9 to 93.3+/-8.4 cm(2), p<0.01) and pulse wave velocity (from 1,706+/-52 to 1,587+/-51 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum high-density lipoprotein cholesterol (from 5.06+/-0.15 to 5.32+/-0.13 mmol/L, p<0.05) and adiponectin levels (from 8.27+/-0.76 to 9.13+/-0.81 microg/mL, p<0.05) were observed. Also, there were reductions in the interleukin-6 level (from 2.26+/-0.27 to 1.60+/-0.14 pg/mL, p<0.01). We also conducted these investigations in male subjects alone and similar findings were obtained for all of these parameters. In conclusion, telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin.


Subject(s)
Adiponectin/blood , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Benzimidazoles/therapeutic use , Benzoates/therapeutic use , C-Reactive Protein/metabolism , Hypertension/drug therapy , Interleukin-6/blood , Intra-Abdominal Fat/metabolism , Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/pharmacology , Benzoates/pharmacology , Blood Pressure/physiology , Cholesterol, HDL/blood , Female , Humans , Hypertension/complications , Hypertension/metabolism , Insulin Resistance/physiology , Intra-Abdominal Fat/drug effects , Japan , Male , Middle Aged , PPAR gamma/agonists , Regional Blood Flow/physiology , Telmisartan , Vasculitis/blood , Vasculitis/etiology , Vasculitis/physiopathology
SELECTION OF CITATIONS
SEARCH DETAIL