ABSTRACT
A clinic-based retrospective longitudinal study conducted for 5.8 ± 2.5 years, including 383 (M/F 245/138) Japanese patients with type 2 diabetes mellitus showed that females exhibit a significantly higher prevalence of proliferative diabetic retinopathy (DR) at baseline and that female gender is an independent risk factor for the development of DR.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Disease Progression , Female , Follow-Up Studies , Humans , Incidence , Japan/epidemiology , Longitudinal Studies , Male , Middle Aged , Pilot Projects , Prognosis , Retrospective Studies , Risk Factors , Sex FactorsABSTRACT
Ergosterol (ERG) is a sterol produced by most fungi, but not by most plants. Thus, measurement of ERG in cereals makes it possible to determine the presence of fungi in cereals that can cause quality problems, such as mycotoxin contamination. This study developed and performed a single-laboratory validation for a method to test for ERG in various cereals. ERG was extracted by refluxing samples for 1 h with methanol-sodium hydroxide. ERG was extracted from the extract with hexane and then purified using a silica gel cartridge column. ERG was then separated and detected by reverse-phase high-performance liquid chromatography (HPLC). 'Within-day' recoveries of ERG at low levels were 92-99% with relative standard deviations (RSDs) of 3.2-6.5%. 'Between-day' recoveries of ERG at low levels were 97% and RSDs were 4.2-10.2%, respectively. Average recoveries of ERG over the range from 1.0 to 100.0 mg kg(-1) were 81-105% and RSDs were 3.9-16.3%.
Subject(s)
Chromatography, High Pressure Liquid/methods , Edible Grain/chemistry , Ergosterol/analysis , Food Contamination/analysis , Mycotoxins/analysis , Spores, Fungal/chemistry , Edible Grain/microbiology , JapanABSTRACT
OBJECTIVE: Identification of the genes responsible for systemic lupus erythematosus (SLE). METHODS: All the exons and putative promoter regions of 53 candidate genes (TNFRSF6/Fas, TNFSF6/FasL, Fli1, TNFSF10/TRAIL, TNFSF12/TWEAK, Bcl-2, PTEN, FADD, TRADD, CDKN1A, TNFRSF1A/TNFR1, TNFRSF4/OX40, TNFSF4/OX40L, TNFSF5/CD40L, TNFSF13B/BAFF, ICOS, CTLA4, CD28, FYN, G2A, CR2, PTPRC/CD45, CD22, CD19, Lyn, PDCD1, PTPN6, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, CD3Z, DNASE1, APCS, MERTK, C3, C1QA, C1QB, C1QG, C2, MBL2, IGHM, IL-2, IL-4, IL-10, IFNG, TNFA, MAN2A1, TNFRSF11A/RANK, TNFRSF11B/OPG, TNFSF11/OPGL) were screened for single nucleotide polymorphisms (SNPs) and their association with SLE was assessed by case-control studies. A total of 509 cases and 964 controls of Japanese descent were enrolled. RESULTS: A total of 316 SNPs was identified. When analysed in the Japanese population, the allele frequencies of T at rs7951 and G at rs2230201 of the C3 gene were 0.110 and 0.626, respectively, in SLE patients; significantly higher than the frequencies of 0.081 and 0.584, respectively, in controls [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.05-1.86, P = 0.016 and OR=1.19, 95% CI = 1.01-1.41, P = 0.038, respectively]. The mean serum C3 level of carriers of the rs7951 T allele was significantly lower than that of non-carriers of the T allele in 87 SLE patients whose medical records were available (P = 0.0018). CONCLUSION: rs7951 T allele of the C3 gene was significantly associated with SLE, and decreased serum level of C3 seems to be correlated with this allele.
Subject(s)
Complement C3/genetics , Genetic Predisposition to Disease , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Complement System Proteins/genetics , DNA/genetics , DNA/immunology , Exons , Gene Frequency , Genotype , Humans , Interleukins/genetics , Japan , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Promoter Regions, GeneticABSTRACT
A growing body of evidence indicates that genetic factors are involved in an increased risk of infection. We investigated whether mannose-binding lectin (MBL) gene polymorphisms that cause low levels of MBL are associated with the occurrence of major infections in patients, mainly bearing hematological malignancies, after high-dose chemotherapy (HDT) rescued by autologous peripheral blood stem cell transplantation (auto-PBSCT). A retrospective evaluation of 113 patients treated with HDT and auto-PBSCT revealed that the low-producing genotypes, B/B and B/LXA, were associated with major bacterial infection (P=0.0016, OR 7.9). We next performed a nation-wide large-scale study to assess the allele frequency of the MBL coding mutation in a total of 2623 healthy individuals in Japan. The frequency of allele B was estimated to be approximately 0.2, almost the same in seven different areas of Japan. This common occurrence suggests that MBL deficiency may play an important role in the clinical settings of immunosuppression.
Subject(s)
Bacterial Infections/genetics , Genetic Predisposition to Disease , Hematologic Neoplasms/therapy , Mannose-Binding Lectin/genetics , Peripheral Blood Stem Cell Transplantation , Polymorphism, Genetic , Alleles , Bacterial Infections/etiology , Case-Control Studies , Female , Gene Frequency , Genetic Linkage , Hematologic Neoplasms/complications , Humans , Male , Transplantation, HomologousABSTRACT
OBJECTIVE: To determine whether serum levels of a proliferation-inducing ligand (APRIL) are raised in patients with systemic lupus erythematosus (SLE) and correlate with autoantibody titres or disease activity, or both. METHODS: Serum samples from 48 patients with SLE, 41 normal healthy subjects, and 21 patients with rheumatoid arthritis (RA) were assayed for APRIL by enzyme linked immunosorbent assay. Medical charts were retrospectively reviewed for autoantibody titres and immunoglobulin levels. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. RESULTS: The APRIL levels in the serum samples from patients with SLE were significantly higher than in those from healthy controls and those from patients with RA. Serum APRIL levels did not correlate with serum IgG and IgM levels, but had a tendency to correlate with anti-double stranded DNA antibody titres. Moreover, serum APRIL levels correlated significantly with musculoskeletal manifestations among patients with SLE when assessed by the BILAG index. CONCLUSION: APRIL may be an important factor in raised autoantibody titres and musculoskeletal disease in patients with SLE. Patients with raised serum APRIL levels may be ideal candidates for therapeutic targeting of APRIL.
Subject(s)
Lupus Erythematosus, Systemic/blood , Membrane Proteins/blood , Adult , Arthritis, Rheumatoid/blood , Autoantibodies/blood , Biomarkers/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Statistics, Nonparametric , Tumor Necrosis Factor Ligand Superfamily Member 13 , Tumor Necrosis Factor-alphaABSTRACT
We report the first direct observation of ferromagnetic spin polarization of Au nanoparticles with a mean diameter of 1.9 nm using x-ray magnetic circular dichroism (XMCD). Owing to the element selectivity of XMCD, only the gold magnetization is explored. Magnetization of gold atoms as estimated by XMCD shows a good agreement with results obtained by conventional magnetometry. This evidences intrinsic spin polarization in nanosized gold.
ABSTRACT
We report a case of adenofibroma of the endometrium in a 69-year-old woman. This patient was receiving tamoxifen therapy after surgery for breast cancer. Magnetic resonance imaging showed an intracavitary mass containing multiple cystic components. We suggest adenofibroma as a possible diagnosis in cases of uterine masses with multiple cystic components and no clinical evidence of malignancy.
Subject(s)
Adenofibroma/diagnosis , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Endometrial Neoplasms/diagnosis , Magnetic Resonance Imaging , Neoplasms, Second Primary/diagnosis , Tamoxifen/therapeutic use , Aged , Female , HumansABSTRACT
Human herpesvirus 6 (HHV-6) infection and disease are serious complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV) is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has not been well characterized in vivo. We retrospectively compared the HHV-6 reactivation rate in pediatric allo-SCT recipients with and without GCV prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients without prophylactic GCV administration was significantly higher than that in those receiving prophylactic GCV (11/28 vs 0/13, P < 0.01). Five of 36 patients without prophylactic GCV showed clinical manifestations including skin rash, interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed in one of the 13 patients receiving prophylactic GCV. This patient showed fever, diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA copy number. Patients who received GCV for treatment of HHV-6 infection showed an improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is effective for treating HHV-6 disease after allo-SCT in vivo.
Subject(s)
Antiviral Agents/therapeutic use , Ganciclovir/therapeutic use , Hematopoietic Stem Cell Transplantation , Herpesvirus 6, Human/drug effects , Roseolovirus Infections/prevention & control , Child , DNA, Viral/blood , Drug Evaluation , Female , Herpes Zoster/prevention & control , Herpesvirus 6, Human/growth & development , Herpesvirus 6, Human/isolation & purification , Humans , Male , Polymerase Chain Reaction , Retrospective Studies , Roseolovirus Infections/drug therapy , Roseolovirus Infections/epidemiology , Roseolovirus Infections/mortality , Transplantation, Homologous , Viremia/drug therapy , Virus Activation/drug effectsABSTRACT
We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the beta2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA.
Subject(s)
Antiviral Agents/administration & dosage , Cytomegalovirus Retinitis/therapy , Drug Resistance, Viral , Foscarnet/administration & dosage , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Child , Cytomegalovirus/genetics , Cytomegalovirus Retinitis/diagnosis , Cytomegalovirus Retinitis/etiology , Female , Ganciclovir/administration & dosage , Humans , Infant , Nucleic Acid Amplification Techniques , RNA, Viral/bloodABSTRACT
An unusual alkaloid, the 2-aza-anthraquinone derivative, 5-deoxy-7-methyl bostrycoidin, was identified in the cultures of the spore-derived mycobionts of the lichen Haematomma sp., but not in the natural lichen thallus.
Subject(s)
Fungi/chemistry , Isoquinolines/isolation & purification , Lichens , Isoquinolines/chemistry , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
We report a rare case of posterior mediastinal esophageal cyst associated with pulmonary anomaly that had no connection with the proper esophagus, on either CT or MRI, and suggest including this entity in the differential diagnosis of posterior mediastinal masses.
Subject(s)
Esophageal Cyst/diagnosis , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Adolescent , Diagnosis, Differential , Esophageal Cyst/complications , Esophageal Cyst/pathology , Humans , Lung Diseases/complications , Lung Diseases/diagnosis , Lung Diseases/pathology , Male , Mediastinal Neoplasms/diagnosisABSTRACT
BACKGROUND: Human herpesvirus 6 (HHV-6), a causative virus of exanthem subitum, may occasionally present with a severe clinical form in immunosuppressed patients after transplantation. In this study, HHV-6 DNA was sequentially measured with a polymerase chain reaction (PCR) method, a quick and sensitive modality in pediatric living-related liver transplantation (LTx). METHODS: Subjects consisted of 5 post-operative biliary atresia patients undergoing living-related LTx at ages from 8 months to 4 yr. Immunosuppression was performed with Tacrolimus (blood trough level 8-18 within 1 month and 5-10 ng/mL thereafter) and low-dose steroid. Specimens were peripheral blood mononuclear cells (PBMC), plasma, and liver biopsy tissue. The amount of HHV-6 DNA was semiquantified as follows: 1+, 1-10; 2+, 10-100; 3+, 100-1000; 4+, over 1000 copies/105 PBMCs. RESULTS: A total of 69 blood samples and three liver biopsies were provided for the examination. HHV-6 DNA in PBMC was positive in 2 donors and 3 recipients before LTx. Two patients with negative DNA were converted to 3+ at 2-3 wk after LTx and 3 with positive DNA remained 2+ to 3+ throughout the post-LTx period. Only 1 patient developed clinical symptoms, such as fever, liver dysfunction, petechiae, idiopathic thrombocytopenic purpura, and finally bone marrow suppression. HHV-6 DNA in the liver biopsy tissue and plasma in this patient were 4+ and 2+, respectively. CONCLUSION: HHV-6 DNA in PBMC measured by the PCR method may be persistently high in pediatric recipients after living-related LTx. Although HHV-6 DNA in PBMC may be positive in case of evident infection, positivity in PBMC may not be always associated with the clinical symptoms.
Subject(s)
DNA, Viral/isolation & purification , Herpesviridae Infections/diagnosis , Herpesvirus 6, Human/isolation & purification , Liver Transplantation , Exanthema Subitum/diagnosis , Herpesvirus 6, Human/genetics , Humans , Immunosuppressive Agents/therapeutic use , Infant , Living Donors , Polymerase Chain Reaction , Prospective StudiesABSTRACT
Membrane fusion is a key event in vesicular trafficking in every cell, and many fusion-related proteins have been identified. However, how the actual fusion event occurs has not been elucidated. By using molecular dynamics simulations we found that when even a small region of two membranes is closely apposed such that only a limited number of water molecules remain in the apposed area (e.g., by a fusogenic protein and thermal membrane fluctuations), dramatic lipid disorientation results within 100 ps-2 ns, which might initiate membrane fusion. Up to 12% of phospholipid molecules in the apposing layers had their alkyl chains outside the hydrophobic region, lying almost parallel to the membrane surface or protruding out of the bilayer by 2 ns after two membranes were closely apposed.
Subject(s)
Cell Membrane/chemistry , Cell Membrane/metabolism , Membrane Fusion , Membrane Lipids/metabolism , Models, Molecular , Computer Simulation , Hydrocarbons/chemistry , Hydrocarbons/metabolism , Hydrogen Bonding , Molecular Conformation , Static Electricity , Water/metabolismABSTRACT
The authors report two cases of malignant peripheral nerve sheath tumors arising from the vagus nerve in the mediastinum in patients who had no stigmata of neurofibromatosis (von Recklinghausen's disease). Computed tomography showed homogeneous soft tissue masses, with minimal calcification seen in one patient. T2-weighted magnetic resonance images showed regions of low signal intensity caused by a dense cellular population.
Subject(s)
Cranial Nerve Neoplasms/pathology , Mediastinum/pathology , Nerve Sheath Neoplasms/pathology , Vagus Nerve Diseases/pathology , Adult , Cranial Nerve Neoplasms/diagnostic imaging , Humans , Male , Middle Aged , Nerve Sheath Neoplasms/diagnostic imaging , Preoperative Care , Tomography, X-Ray Computed , Vagus Nerve Diseases/diagnostic imagingABSTRACT
Treatment of potato tuber tissues with beta-1,3-glucooligosaccharide induces accumulation of (S)-N-p-coumaroyloctopamine (p-CO). We examined the role of reactive oxygen species (ROS) and nitric oxide (NO) in the signal transduction leading to p-CO accumulation. Induction was suppressed by an NADPH-oxidase inhibitor, diphenyleneiodonium chloride, and oxygen radical scavengers. H2O2 was generated in the tuber tissue within a few minutes of treatment with beta-1,3-glucooligosaccharide. On the other hand, treatment with NO specific scavenger, nitric oxide synthase inhibitor, and serine protease inhibitor did not inhibit p-CO induction. Our findings suggest that ROS generated by the action of NADPH-oxidase play an important role in this system, while NO and serine protease are unlikely to be involved in this process.
Subject(s)
Coumaric Acids/metabolism , Octopamine/analogs & derivatives , Octopamine/metabolism , Oligosaccharides/pharmacology , Reactive Oxygen Species/metabolism , Solanum tuberosum/metabolism , 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology , Enzyme Inhibitors/pharmacology , Glucans , Glucose , Hydrogen Peroxide/metabolism , NADPH Oxidases/metabolism , Onium Compounds/pharmacology , Phenylalanine Ammonia-Lyase/metabolism , Polysaccharides/pharmacology , Signal Transduction , Solanum tuberosum/drug effects , Tyrosine Decarboxylase/metabolismABSTRACT
We report a case of right-sided aortic arch with isolation of the left subclavian artery diagnosed using computed tomography (CT). This was a rare type in which the left subclavian artery, originating from the pulmonary artery via the arterial duct, was isolated after closure of the ductus. Collateral circulation was considered to be obtained mainly from the left intercostal artery via the costocervical trunk through the supreme intercostal artery.
Subject(s)
Aorta, Thoracic/abnormalities , Subclavian Artery/abnormalities , Tomography, X-Ray Computed , Aorta, Thoracic/diagnostic imaging , Collateral Circulation , Humans , Male , Middle Aged , Subclavian Artery/diagnostic imagingABSTRACT
AM-toxins are host-specific phytotoxins of the Alternaria alternata apple pathotype, which induce necrosis on apple leaves. In this study, we developed a new assay to measure the necrotic activity of AM-toxin analogs using cultured leaves from meristem cells. This method was not only more sensitive to AM-toxin I, but also more reliable than the previous one that used tree leaves due to the homogeneous nature of cultured leaves and to the method of application of toxins. Using this assay method we investigated a structure-activity relationship of AM-toxin analogs synthesized in this study. Most residues and the macrocyclic ring structure were strictly recognized by AM-toxin putative receptor, whereas the L-Ala binding subsite of the receptor allowed for side chain structures with various stereoelectronic properties. These findings are important for designing ligands for further experimental probing of the nature of the receptor.
Subject(s)
Alternaria/chemistry , Fruit/drug effects , Meristem/drug effects , Mycotoxins/chemistry , Peptides, Cyclic/chemistry , Binding Sites , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mycotoxins/pharmacology , Peptides, Cyclic/pharmacology , Plant Diseases/microbiology , Species Specificity , Structure-Activity RelationshipABSTRACT
This report addresses the following problems associated with the generation of computer models of phospholipid bilayer membranes using molecular dynamics simulations: arbitrary initial structures and short equilibration periods, an Ewald-induced strong coupling of phospholipids, uncertainty regarding which value should be used for surface tension to alleviate the problem of the small size of the membrane, and simultaneous realization of both order parameters and the surface area. We generated a computer model of the liquid-crystalline L-alpha-dimyristoylphosphatidylcholine (DMPC) bilayer, starting from a configuration based on a crystal structure (rather than from an arbitrary structure). To break the crystalline structure, a 20-ps high-temperature pulse of 510 K (but not 450 or 480 K) was effective. The system finally obtained is an all-atom model, with Ewald summation to evaluate Coulombic interactions and a constant surface tension of 35 dynes/cm/water-membrane interface, equilibrated for 12 ns (over 50 ns total calculation time), which reproduces all of the experimentally observed parameters examined in this work. Furthermore, this model shows the presence of significant orientational correlations between neighboring alkyl chains and between shoulder vectors (which show the orientations of the lipids about their long axes) of neighboring DMPCs.
Subject(s)
Dimyristoylphosphatidylcholine/chemistry , Lipid Bilayers/chemistry , Computer Simulation , Hot Temperature , Kinetics , Models, Molecular , Molecular Conformation , Thermodynamics , WaterABSTRACT
Potato tuber disks, when treated with laminarin, a beta-1,3-glucooligosaccharide from Laminaria digitata, accumulate a hydroxycinnamoyl amide compound, N-p-coumaroyloctopamine (p-CO). The biosynthesis of p-CO was investigated by feeding experiments, in order to show that the precursors of N-p-coumaroyl and octopamine moieties of p-CO are L-phenylalanine and L-tyrosine, respectively. The treatment of potato tuber tissue with laminarin resulted in elevated activities of four enzymes which are putatively involved in p-CO biosynthesis: phenylalanine ammonia lyase (PAL; EC 4.3.1.5), 4-hydroxycinnamic acid:CoA ligase (4CL; EC 6.2.1.12), hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110) and tyrosine decarboxylase (TyrDC; EC 4.1.1.25). Among these, the response of TyrDC was specific to laminarin treatment, thus indicating that the regulation of TyrDC activity is critical for the accumulation of p-CO in potato tuber tissue.
Subject(s)
Coumaric Acids/metabolism , Octopamine/analogs & derivatives , Polysaccharides/pharmacology , Solanum tuberosum/enzymology , Acyltransferases/metabolism , Coenzyme A Ligases/metabolism , Enzyme Activation , Glucans , Kinetics , Octopamine/metabolism , Phenylalanine Ammonia-Lyase/metabolism , Plant Roots/enzymology , Tyrosine Decarboxylase/metabolismABSTRACT
OBJECTIVE: The presence of diabetes could possibly have an adverse influence on the late results of coronary artery bypass grafting (CABG). A retrospective observational risk-unadjusted estimation study was conducted to clarify the magnitude of this unfavorable influence of diabetes based on our experience at Juntendo University. METHODS: Between January 1984 and December 1995, 1,618 primary CABG operations were performed and 99.0% of these patients were followed up for a mean period of 81.2 months with a maximal follow-up of 14 years. Among the 1,610 patients who were successfully followed up, 523 patients (32.5%) were diabetic and this cohort was compared with 1,087 nondiabetic patients regarding the patient profiles, perioperative outcome, and the long-term outcome. RESULTS: Diabetic patients included a higher proportion of females, a greater preoperative presence of renal insufficiency, a higher rate of three vessel disease, and reception of a greater number of grafts (mean: 2.5 versus 2.4) and an internal thoracic artery graft (68% versus 58%). Hospital mortality was not significantly different (2.1% vs 1.0%: ns). An actuarial analysis revealed a significantly unfavorable long-term survival in the diabetic group (59.6%) at 14 years, compared with the nondiabetic group (73.4%), however diabetic patients with an internal thoracic artery graft had a favorable long-term survival (82.0%) at 13 years, and this finding was almost identical to that of nondiabetic patients with an internal thoracic artery graft (88.5%). CONCLUSION: We conclude that the presence of diabetes appears to be a major risk factor in patients undergoing CABG. However, diabetic patients with an internal thoracic artery graft had a survival almost identical to that of nondiabetic patients with an internal thoracic artery graft.