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Biomedical subjects

A Saito

Publications and source records attributed to A Saito.

At least 127 records · Page 7Linked to original sources

Enhanced gamma interferon production through activation of Valpha14(+) natural killer T cells by alpha-galactosylceramide in interleukin-18-deficient mice with systemic cryptococcosis.

We showed recently that activation of Valpha14(+) natural killer T cells (NKT cells) by alpha-galactosylceramide (alpha-GalCer) resulted in increased gamma interferon (IFN-gamma) production and host resistance to intravenous infection with Cryptococcus neoformans. In other studies, interleukin-18 (IL-18) activated NKT cells in collaboration with IL-12, suggesting the possible contribution of this cytokine to alpha-GalCer-induced IFN-gamma synthesis. Here we examined the role of IL-18 in alpha-GalCer-induced Th1 response by using IL-18KO mice with this infection. In these mice, levels of IFN-gamma in serum and its synthesis in vitro by spleen cells stimulated with live organisms were not reduced, but rather enhanced, compared to those in wild-type (WT) mice, while such production was completely absent in IL-12KO mice. The enhanced production of IFN-gamma correlated with increased IL-12 synthesis but not with reduced production of IL-4, which was rather increased. IFN-gamma synthesis in IL-18KO mice was abolished by neutralizing anti-IL-12 antibody and significantly inhibited by neutralization of endogenous IL-4 with a specific monoclonal antibody. In addition, administration of recombinant IL-4 significantly enhanced the production of IFN-gamma in WT mice. Finally, the enhanced production of IFN-gamma in IL-18KO mice correlated with increased host defense against cryptococcal infection, as indicated by enhancement in alpha-GalCer-related clearance of microorganisms. Our results indicated that in IL-18KO mice, IFN-gamma synthesis was enhanced through overproduction of IL-12 and IL-4 after intravenous infection with C. neoformans and a ligand-specific activation of Valpha14(+) NKT cells.

Animals↗

In vivo selection of T-cell receptor junctional region sequences by HLA-A2 human T-cell lymphotropic virus type 1 Tax11-19 peptide complexes.

Using HLA-peptide tetrameric complexes, we isolated human T-cell lymphotrophic virus type 1 Tax peptide-specific CD8(+) T cells ex vivo. Antigen-specific amino acid motifs were identified in the T-cell receptor Vbeta CDR3 region of clonally expanded CD8(+) T cells. This result directly confirms the importance of the CDR3 region in determining the antigen specificity in vivo.

Amino Acid Motifs↗

Head and neck lesions: characterization with diffusion-weighted echo-planar MR imaging.

PURPOSE: To evaluate whether apparent diffusion coefficients (ADCs) calculated from diffusion-weighted echo-planar magnetic resonance (MR) images can be used to characterize head and neck lesions. MATERIALS AND METHODS: Diffusion-weighted echo-planar MR imaging was performed with a 1.5-T MR unit in 97 head and neck lesions in 97 patients. Images were obtained with a diffusion-weighted factor, factor b, of 0, 500, and 1,000 sec/mm(2), and an ADC map was constructed. The ADCs of lesions, cerebrospinal fluid, and spinal cord were calculated. RESULTS: Acceptable images for ADC measurement were obtained in 81 (84%) patients. The mean ADC of malignant lymphomas, (0.66 +/- 0.17[SD]) x 10(-3) mm(2)/sec (n = 13), was significantly smaller (P <.001) than that of carcinomas. The mean ADC of carcinomas, (1.13 +/- 0.43) x 10(-3) mm(2)/sec (n = 36), was significantly smaller (P =.002) than that of benign solid tumors. The mean ADC of benign solid tumors, (1.56 +/- 0.51) x 10(-3) mm(2)/sec (n = 22), was significantly smaller (P =.035) than that of benign cystic lesions, (2.05 +/- 0.62) x 10(-3) mm(2)/sec (n = 10). No significant differences were seen in the mean ADC of cerebrospinal fluid and of spinal cord among four groups of lesions. When an ADC smaller than 1.22 x 10(-3) mm(2)/sec was used for predicting malignancy, the highest accuracy of 86%, with 84% sensitivity and 91% specificity, was obtained. CONCLUSION: Measurement of ADCs may be used to characterize head and neck lesions.

Adolescent↗

Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B activation in skeletal muscle.

To determine the molecular mechanism underlying hyperglycemia-induced insulin resistance in skeletal muscles, postreceptor insulin-signaling events were assessed in skeletal muscles of neonatally streptozotocin-treated diabetic rats. In isolated soleus muscle of the diabetic rats, insulin-stimulated 2-deoxyglucose uptake, glucose oxidation, and lactate release were all significantly decreased compared with normal rats. Similarly, insulin-induced phosphorylation and activation of Akt/protein kinase B (PKB) and GLUT-4 translocation were severely impaired. However, the upstream signal, including phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and -2 and activity of phosphatidylinositol (PI) 3-kinase associated with IRS-1/2, was enhanced. The amelioration of hyperglycemia by T-1095, a Na(+)-glucose transporter inhibitor, normalized the reduced insulin sensitivity in the soleus muscle and the impaired insulin-stimulated Akt/PKB phosphorylation and activity. In addition, the enhanced PI 3-kinase activation and phosphorylation of IR and IRS-1 and -2 were reduced to normal levels. These results suggest that sustained hyperglycemia impairs the insulin-signaling steps between PI 3-kinase and Akt/PKB, and that impaired Akt/PKB activity underlies hyperglycemia-induced insulin resistance in skeletal muscle.

Animals↗

Prevalence of human immunodeficiency virus, hepatitis B and hepatitis C virus antibodies and hepatitis B antigen among commercial sex workers in Japan.

OBJECTIVE: To investigate the prevalence of antibodies to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and of hepatitis B surface (HBs) antigen in commercial sex workers (CSW) who attended a sexually transmitted disease (STD) clinic in Tokyo. METHODS: Surveys were conducted on 308 CSW and 384 control subjects for HIV antibody or 241 control subjects for HBs antibody and antigen and HCV antibody. RESULTS: HIV antibody was not detected in either CSW or control subjects. The positive rates for HBs antigen and antibody were 0.6 and 23.4%, respectively, in the CSW group, and 0.4 and 71.8% in the control group. The HCV antibody positive rate was 3.2% in the CSW group and 0.4% in the control group. CONCLUSION: A statistically significant difference between the two groups was observed only in HCV antibody positive rate. STD checkup for CSW alone is inadequate--STD health education and screening for the general public are also required.

Adult↗

Transgenic CuZn-superoxide dismutase inhibits NO synthase induction in experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The expression of inducible NO synthase (iNOS) after experimental subarachnoid hemorrhage (SAH) has been postulated to play a critical role in the pathogenesis of SAH and subsequent cerebral vasospasm. The inhibitory effect of CuZn-superoxide dismutase (CuZn-SOD) on the induction of iNOS after SAH was examined by using transgenic mice overexpressing CuZn-SOD. METHODS: SOD-transgenic mice and nontransgenic littermates were subjected to SAH by endovascular perforation of the left anterior cerebral artery. The iNOS mRNA expression after SAH was determined by reverse transcription-polymerase chain reaction, and the distribution of iNOS-positive cells was immunohistochemically examined. The nuclear expression of activated nuclear factor-kappaB, a major transcription factor of iNOS gene, was also immunohistochemically examined. RESULTS: In nontransgenic mice, SAH-induced iNOS protein and mRNA expressions in the arteries of basal cistern as well as in the cerebral cortex were demonstrated by immunohistochemistry and reverse transcription-polymerase chain reaction. SAH-induced iNOS protein and mRNA expressions in those tissues were much reduced in SOD-transgenic mice compared with nontransgenic mice. Moreover, the nuclear expression of the activated form of nuclear factor-kappaB was immunohistochemically detected in the cerebral cortices of nontransgenic mice but not in those of SOD-transgenic mice. CONCLUSIONS: These results indicate that oxygen-derived free radicals, particularly superoxide, play an important role in the iNOS gene expression after SAH and provide a molecular basis for the protective role of SOD against vasospasm after SAH.

Animals↗

Oxygenation reactions of various tricyclic fused aromatic compounds using Escherichia coli and Streptomyces lividans transformants carrying several arene dioxygenase genes.

Bioconversion (biotransformation) experiments on arenes (aromatic compounds), including various tricyclic fused aromatic compounds such as fluorene, dibenzofuran, dibenzothiophene, carbazole, acridene, and phenanthridine, were done using the cells of Escherichia coli transformants expressing several arene dioxygenase genes. E. coli carrying the phenanthrene dioxygenase (phdABCD) genes derived from the marine bacterium Nocardioides sp. strain KP7 converted all of these tricyclic aromatic compounds, while E. coli carrying the Pseudomonas putida F1 toluene dioxygenase (todC1C2BA) genes or the P. pseudoalcaligenes KF707 biphenyl dioxygenase (bphA1A2A3A4) genes was not able to convert these substrates. Surprisingly, E. coli carrying hybrid dioxygenase (todC1::bphA2A3A4) genes with a subunit substitution between the toluene and biphenyl dioxygenases was able to convert fluorene, dibenzofuran, and dibenzothiophene. The cells of a Streptomyces lividans transformant carrying the phenanthrene dioxygenase genes were also evaluated for bioconversion of various tricyclic fused aromatic compounds. The ability of this actinomycete in their conversion was similar to that of E. coli carrying the corresponding genes. Products converted from the aromatic compounds with these recombinant bacterial cells were purified by column chromatography on silica gel, and identified by their MS and 1H and 13C NMR analyses. Several products, e.g., 4-hydroxyfluorene converted from fluorene, and cis-1,2-dihydroxy-1,2-dihydrophenanthridine, cis-9,10-dihydroxy-9,10-dihydrophenanthridine, and 10-hydroxyphenanthridine, which were converted from phenanthridine, were novel compounds.

Actinomycetales↗

Reduction of the infectivity of Toxoplasma gondii and Eimeria stiedai sporozoites by treatment with bovine lactoferricin.

Sporozoites of Toxoplasma gondii preincubated with lactoferricin showed decreased activity in penetration of mouse embryonal cells. Mice inoculated with 10(5) sporozoites preincubated with lactoferricin showed a higher survival rate than those inoculated with the same number of untreated sporozoites. Likewise, sporozoites of Eimeria stiedai preincubated with lactoferricin also showed decreased activity in penetration of rabbit hepatobiliary cells. Rabbits inoculated with 10(5) sporozoites preincubated with lactoferricin shed fewer oocysts than those inoculated with the same number of untreated sporozoites. These results indicate that lactoferricin is effective to reduce the infectivity of sporozoites of Toxoplasma gondii and Eimeria stiedai.

Animals↗

Identification and the role of soluble antigens detected in bile from Eimeria stiedai-infected rabbits.

Antibodies against Eimeria stiedai sporozoites and merozoites were detected in the sera of rabbits immunized with bile obtained from infected rabbits on the 15th day post-infection. The trails made by gliding sporozoites were also detected by the sera. After penetration into the host cell, an antibody-binding region was observed on the parasitophorous vacuole membranes of the parasites. Rabbits administered a combination of the bile and cholera toxin shed fewer oocysts in the feces after infection than control rabbits. The immunized rabbits developed a high level of IgA antibody against soluble antigens in the bile. By immunoblotting, antigens with molecular masses of 32, 37, and 49 kDa were detected in the bile obtained from infected rabbits on the 15th day postinfection. Absorption treatment with sporozoites reduced or abolished the antibody reactivity to the 32-kDa antigen of merozoites and the bile antigens. However, antibody reactivity to the 37- and 49-kDa antigens still remained. These results indicate that soluble antigens are present in the bile of rabbits in the acute phase of infection, and these may be produced and released by merozoites during the host cell invasion process.

Animals↗

Naturally-occurring Neospora caninum infection in an adult sheep and her twin fetuses.

Neospora caninum tissue cysts were found in the brains of surgically delivered twin fetuses at 119 days of gestation. In the brains of both fetuses, there was an inflammatory reaction involving perivascular cuffings of mononuclear cells, glial nodules. The dam of these fetuses died because of metritis. Histopathological examination of the ewe revealed N. caninum tissue cysts and focal gliosis with mononuclear cell cuffings. A N. caninum-specific DNA fragment was detected in a brain homogenate of the ewe by the polymerase chain reaction method. This is the first report of N. caninum infection in twin ovine fetuses and in an adult sheep.

Animals↗

Isolation of Neospora caninum from the brain of a pregnant sheep.

Neospora caninum was isolated from the brain of a naturally infected pregnant sheep by inoculation of immunodeficient mice with a homogenate of the brain tissue. The ewe showed no clinical signs. Tachyzoites were observed in the tissues of the nu/nu mice injected with the brain tissue homogenate and the diagnosis was confirmed by immunohistochemical staining with anti-N. caninum antibodies and by detecting N. caninum-specific DNA by polymerase chain reaction.

Animals↗

Expression of cytokines and inducible nitric oxide synthase in inflamed gingival tissue.

BACKGROUND: Periodontopathic bacteria induce inflammation of periodontal tissues. The cytokines and nitric oxide released in periodontal lesions have been reported to play a protective role in bacterial infection and to relate to the process of inflammation. To clarify the relationship between colonization of periodontopathic bacteria and cytokines, we evaluated profiles of inflammatory cytokines, chemokine, anti-inflammatory cytokines, and inducible nitric oxide synthase (iNOS) and colonization by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, which are major pathogens of periodontitis. METHODS: mRNA expression of cytokines and iNOS in inflamed and healthy gingival tissue was determined using reverse transcription-polymerase chain reaction (RT-PCR), and the relationship between their profiles and the detection of specific bacteria was analyzed. RESULTS: The relative expression of interleukin (IL)-6 and iNOS mRNAs in periodontal lesions was significantly higher than those in healthy individuals. IL-6 mRNA expression was also significantly higher at bleeding on probing (BOP)-positive sites than at BOP-negative sites. The expressions of IL-1alpha and IL-8 increased, but IL-10 expression decreased at sites where A. actinomycetemcomitans was detected. We found no correlation between the expression of cytokine and iNOS mRNA and infection by P. gingivalis. CONCLUSIONS: The expression of IL-6 may reflect inflammation in gingival tissue, and iNOS may be involved in the inflammatory process in periodontitis. The presence of A. actinomycetemcomitans or P. gingivalis might relate to the different cytokine profiles of IL-1alpha, IL-8, and IL-10.

Actinobacillus Infections↗

Protein-losing enteropathy exacerbated with the appearance of symptoms of systemic lupus erythematosus.

A 38-year-old woman visited our hospital with edema on her face and conjunctivae. The underlying disease was not clarified, and she did not visit the hospital afterwards. She suffered from diarrhea, polyarthralgia, Raynaud's phenomenon, malar rash and hair loss in the subsequent two years, and was hospitalized because of hypoproteinemia. Her urine, liver and heart test results did not account for her hypoproteinemia. She was diagnosed as having protein-losing enteropathy (PLE) associated with SLE based on the 99mtechnetium-labeled human serum albumin scintigraphy findings, clinical findings and laboratory results of antinuclear and anti-Sm antibodies. This case report demonstrates a strong association between PLE and SLE because PLE was aggravated along with the appearance of SLE symptoms and PLE subsided with prednisolone treatment along with improvement of SLE.

Adult↗

Herpes simplex virus bronchopneumonia in a non-immunocompromized individual.

We report a rare case of herpes simplex virus (HSV) bronchopneumonia in an otherwise healthy middle-aged individual. Bronchoscopy indicated scattered white-coated lesions in the bronchial mucosa. The diagnosis was established following immunohistopathological staining for HSV of specimens obtained by bronchial biopsy. This case suggests that HSV could be a pathological agent of not only oral and genital mucosal lesions but also lower respiratory tract infection.

Bronchopneumonia↗

Association of gene polymorphism of polymeric immunoglobulin receptor and IgA nephropathy.

OBJECTIVE: In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible association of the gene polymorphism of pIgR in the patients with and without IgAN. SUBJECTS AND METHODS: Genomic DNA of peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the pIgR gene were PCR amplified and restriction fragment length polymorphism was determined as A1 and A2 with and without Pvu II site, respectively. RESULTS: The pIgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency of A2 was higher in IgAN than in other renal diseases (A1 and A2; 0.516 and 0.484 in IgAN, 0.641 and 0.359 in others, chi2 = 9.84, P = 0.0017, Odds ratio = 1.71). Moreover, the subjects with A2A2 genotype were associated with a relatively low level of serum IgA only in the patients with IgAN but not in other renal diseases. The difference of allele frequencies was more remarkable in the patients with a serum IgA level of less than 300 mg/dl (A1 and A2; 0.439 and 0.561 in IgAN, 0.702 and 0.298 in others, chi2 = 12.44, P = 0.0004, Odds ratio = 3.01). CONCLUSION: This is the first demonstration of the pIgR gene polymorphisms in IgAN which are associated with its clinical phenotype. Gene polymorphisms of pIgR may be candidate genetic markers of susceptibility to IgAN.

Alanine↗

Parotid masses: prediction of malignancy using magnetization transfer and MR imaging findings.

OBJECTIVE: We determined the most accurate criteria for predicting malignancy of masses in the parotid gland using magnetization transfer ratios. SUBJECTS AND METHODS: Lesion-to-muscle magnetization transfer ratios obtained with a spoiled gradient-recalled acquisition in a steady state sequence with a 1-kHz off-resonance pulse were measured in 72 parotid masses (52 benign lesions, 20 malignant tumors). Various MR imaging findings and lesion-to-muscle magnetization transfer ratios were simultaneously assessed using a logistic model to determine the useful factors for predicting malignancy. We also studied the clinical usage of magnetization transfer ratios. RESULTS: Of the MR imaging findings, poorly defined margins showed the highest accuracy, 81%, with 60% sensitivity and 88% specificity. Of the lesion-to-muscle magnetization transfer ratios, a ratio of greater than 0.71 was most accurate (85%), with 90% sensitivity and 83% specificity. All four recurrent tumors and 10 (91%) of 11 secondary tumors were correctly diagnosed using the magnetization transfer ratio analysis. The logistic model revealed that the margin characteristics (p = 0.084) and lesion-to-muscle magnetization transfer ratios (p < 0.001) were statistically significant predictors for malignancy. A combined criteria of poorly defined margins and a lesion-to-muscle magnetization transfer ratio of greater than 0.71 raised the accuracy to 86% and specificity to 96%, but the sensitivity decreased to 60%. CONCLUSION: A combination of MR imaging findings and lesion-to-muscle magnetization transfer ratios was the most accurate predictor of malignancy.

Female↗

Tracheal invasion by thyroid carcinoma: prediction using MR imaging.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of MR imaging in predicting tracheal invasion by thyroid carcinomas and to determine MR imaging criteria for diagnosing tracheal invasion. MATERIALS AND METHODS: MR imaging was performed on the normal trachea of one cadaver and 30 healthy subjects as a standard of reference. Then, MR imaging findings in 67 patients with thyroid carcinoma were reviewed and correlated with surgical and pathologic findings. A logistic regression model was used to determine which MR imaging features were significant for predicting tracheal invasion. RESULTS: Twenty-three (34%) of the 67 patients had tracheal invasion. Logistic regression model analysis revealed that significant MR characteristics for determining tracheal invasion included soft-tissue signal in the tracheal cartilage (p < 0.001), intraluminal mass (p < 0.001), and degree of tumor circumference around the trachea (p = 0.001). The highest accuracy (90%) for determining tracheal invasion was achieved using a combination of findings. A case was considered positive for tracheal invasion if there was soft-tissue signal in the cartilage, an intraluminal mass, or a tumor that abutted a circumference of the trachea of 180 degrees or greater. Using these factors resulted in seven false-positive diagnoses because soft-tissue signal in the cartilage was sometimes seen in healthy trachea. Although intraluminal mass invariably reflected deep tracheal invasion, soft-tissue signal in the cartilage rarely indicated actual cartilage invasion but rather indicated tumor extension between the cartilaginous rings. CONCLUSION: Tracheal invasion by thyroid carcinomas can be accurately diagnosed with MR imaging, and using a combination of criteria is the most accurate method of predicting this phenomenon.

Adult↗