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Biomedical subjects

Hiroyuki Abe

Publications and source records attributed to Hiroyuki Abe.

At least 37 records · Page 2Linked to original sources

High spectral and spatial resolution MRI of breast lesions: preliminary clinical experience.

OBJECTIVE: In previous research, high spectral and spatial resolution (HiSS) echo-planar spectroscopic imaging (EPSI) was successfully applied to the human breast, obtaining improved contrast, anatomic detail, and sensitivity to contrast agents. To test HiSS in the clinical setting, we used HiSS MRI to image 30 women with suspicious breast lesions. SUBJECTS AND METHODS: Women with suspicious breast lesions were scanned before and after contrast administration using EPSI at 1.5 T (0.63-mm in-plane resolution, 2.6-Hz spectral resolution). Images with intensity proportional to the water signal peak height in each voxel were synthesized and compared with standard clinical fat-saturated and early dynamic subtraction images. Pre- and postcontrast HiSS images were compared to assess the effect of the contrast agent on water resonance structure. RESULTS: HiSS images scored significantly better than standard clinical images in lesion conspicuity, margin definition, and internal definition, even though they were acquired before contrast agent injection. Fat suppression was more complete and uniform and detail was shown on HiSS images more clearly than on conventional fat-saturation images. Thus, HiSS images often allowed easier evaluation of the lesion. Contrast agent-affected changes were often spatially and spectrally inhomogeneous. CONCLUSION: HiSS scans were successfully integrated into standard clinical examinations and provided diagnostically useful images before contrast agent injection. Thus, it might be possible to characterize suspicious lesions on the basis of precontrast high-resolution spectral information. This information and information about the effect of contrast agents could potentially improve the specificity of breast MRI.

Adult↗

Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens and T cell infiltration in non-small cell lung carcinoma and their prognostic significance.

Cancer-testis (CT) antigens were identified as a group of highly attractive targets for cancer immunotherapy because of their expression in a variety of malignant tumors but solely in the testis among the normal adult tissues. To evaluate the potential of two members of this family, MAGE-A4 and NY-ESO-1 antigens, for cancer vaccine in non-small cell lung carcinoma (NSCLC), we examined the expression of these antigens and T cell infiltration in tumor tissue, and evaluated their prognostic significance. One hundred fifty-seven patients with NSCLC were studied. Reverse transcription-PCR was performed to evaluate MAGE-A4 and NY-ESO-1 expression. Immunohistochemistry was performed for NY-ESO-1 expression and T cell infiltration into the tumor site. Survival analysis was also performed. MAGE-A4 and NY-ESO-1 were expressed in 40 of 141 (28.4%) and 13 of 157 (8.3%) NSCLC respectively. Both CT antigens were more frequently expressed in squamous cell carcinoma (SCC) than in adenocarcinoma. An inverse correlation was found between MAGE-A4 expression and patient survival in advanced stage cancers. Combined infiltration of both CD4+ and CD8+ T cells into tumor nest predicted better survival. There was no correlation, however, between lymphocyte infiltration and antigen expression in the tumor. MAGE-A4 expression in advanced group and T cell infiltration may provide prognostic information. Lastly, these CT antigens, especially MAGE-A4, may represent potential targets for cancer immunotherapy in patients with NSCLC.

Adult↗

Peptide-induced immune protection of CD8+ T cell-deficient mice against Friend retrovirus-induced disease.

CD8+ CTLs and virus-neutralizing antibodies have been associated with spontaneous and vaccine-induced immune control of retroviral infections. We previously showed that a single immunization with an env gene-encoded CD4+ T cell epitope protected mice against fatal Friend retrovirus infection. Here, we analyzed immune cell components required for the peptide-induced anti-retroviral protection. Mice lacking CD8+ T cells were nevertheless protected against Friend virus infection, while mice lacking B cells were not. Virus-producing cells both in the spleen and bone marrow decreased rapidly in their number and became undetectable by 4 weeks after infection in the majority of the peptide-immunized animals even in the absence of CD8+ T cells. In the vaccinated animals the production and class switching of virus-neutralizing and anti-leukemia cell antibodies were facilitated; however, virus-induced erythroid cell expansion was suppressed before neutralizing antibodies became detectable in the serum. Further, the numbers of virus-producing cells in the spleen and bone marrow in the early stage of the infection were smaller in the peptide-immunized than in unimmunized control mice in the absence of B cells. Thus, peptide immunization facilitates both early cellular and late humoral immune responses that lead to the effective control of the retrovirus-induced disease, but CD8+ T cells are not crucial for the elimination of virus-infected cells in the peptide-primed animals.

Animals↗

Leucine suppresses myofibrillar proteolysis by down-regulating ubiquitin-proteasome pathway in chick skeletal muscles.

In skeletal muscle, amino acids, together with hormones, are key regulators of protein metabolism. Leucine, in particular, has inhibitory effects of protein degradation in skeletal muscles, but the mechanisms are poorly understood. The present study addressed the role of leucine as a regulator of myofibrillar proteolysis in cultured chick myotubes and chick skeletal muscles, and aimed to determine which cellular responses regulate the process. In chick myotubes, leucine suppressed myofibrillar proteolysis (as measured by N(tau)-methylhistidine release), while also decreasing ubiquitin and proteasome C2 subunit mRNA. Oral administration of leucine also suppressed myofibrillar proteolysis (as measured by plasma N(tau)-methylhistidine concentration), while also decreasing proteasome C2 subunit mRNA in chick skeletal muscle. Leucine activated the phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) (but not the mammalian target of rapamycin) inhibition of these pathways and increased myofibrillar proteolysis, ubiquitin and proteasome C2 subunit mRNA. Thus, an important component of muscle proteolysis inhibition by leucine, through the PI3K and PKC, is its ability to suppress transcription of the ubiquitin and proteasome C2 subunit, and degradation of myofibrillar protein.

Animals↗

Development of a functional cDNA array for evaluation of the Th1/Th2 balance.

The immune balance controlled by CD4(+) helper T cell subsets (T helper 1 (Th1) and T helper 2 (Th2)) is crucial for immunoregulation and its imbalance causes various immune diseases including infections, allergic disorders and autoimmune diseases. Therefore, it is of great importance to develop a system of diagnosing Th1/Th2 imbalances for curing immune diseases. Here we developed a functional cDNA array filter useful for assessing the Th1/Th2 balance in mice. To overcome the disadvantages of conventional microarrays carrying thousands of genes, we prepared an array filter containing 40 Th1-specific and 32 Th2-specific genes, which were selected from over 8700 genes based on (i) the specificity of expression in Th1 or Th2 cells and (ii) an expression level which is high enough for detection using a DNA array. This array filter provided a prompt and precise evaluation for the skewing of the Th1/Th2 balance combined with our calculation algorithm. The bias toward Th1 or Th2 was evaluated visually at a glance by aligning the genes on the filter. Moreover, we succeeded in evaluating the skewing of the Th1/Th2 balance in vivo during acute graft versus host disease (GVHD). Thus, this array filter will provide a novel tool for evaluation of the Th1/Th2 balance in a variety of immune diseases.

Acute Disease↗

Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses.

Shigella effectors injected into the host cell via the type III secretion system are involved in various aspects of infection. Here, we show that one of the effectors, IpaH9.8, plays a role in modulating inflammatory responses to Shigella infection. In murine lung infection model, DeltaipaH9.8 mutant caused more severe inflammatory responses with increased pro-inflammatory cytokine production levels than did wild-type Shigella, which resulted in a 30-fold decrease in bacterial colonization. Binding assays revealed that IpaH9.8 has a specific affinity to U2AF(35), a mammalian splicing factor, which interferes with U2AF(35)-dependent splicing as assayed for IgM pre-mRNA. Reducing the U2AF(35) level in HeLa cells and infecting HeLa cells with wild-type caused a decrease in the expression of the il-8, RANTES, GM-CSF, and il-1beta genes as examined by RT-PCR. The results indicate that IpaH9.8 plays a role in Shigella infection to optimize the host inflammatory responses, thus facilitating bacterial colonization within the host epithelial cells.

Animals↗

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians.

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.

Animals↗

False-positive reduction in computer-aided diagnostic scheme for detecting nodules in chest radiographs by means of massive training artificial neural network.

RATIONALE AND OBJECTIVE: We developed a technique that uses a multiple massive-training artificial neural network (multi-MTANN) to reduce the number of false-positive results in a computer-aided diagnostic (CAD) scheme for detecting nodules in chest radiographs. MATERIALS AND METHODS: Our database consisted of 91 solitary pulmonary nodules, including 64 malignant nodules and 27 benign nodules, in 91 chest radiographs. With our current CAD scheme based on a difference-image technique and linear discriminant analysis, we achieved a sensitivity of 82.4%, with 4.5 false positives per image. We developed the multi-MTANN for further reduction of the false positive rate. An MTANN is a highly nonlinear filter that can be trained with input images and corresponding teaching images. To reduce the effects of background levels in chest radiographs, we applied a background-trend-correction technique, followed by contrast normalization, to the input images for the MTANN. For enhancement of nodules, the teaching image was designed to contain the distribution for a "likelihood of being a nodule." Six MTANNs in the multi-MTANN were trained by using typical nodules and six different types of non-nodules (false positives). RESULTS: Use of the trained multi-MTANN eliminated 68.3% of false-positive findings with a reduction of one true-positive result. The false-positive rate of our original CAD scheme was improved from 4.5 to 1.4 false positives per image, at an overall sensitivity of 81.3%. CONCLUSION: Use of a multi-MTANN substantially reduced the false-positive rate of our CAD scheme for lung nodule detection on chest radiographs, while maintaining a level of sensitivity.

False Positive Reactions↗

Computer-aided diagnosis in thoracic CT.

Computer-aided diagnosis (CAD) provides a computerized diagnostic result as a "second opinion" to assist radiologists in the diagnosis of various diseases by use of medical images. CAD has become a practical clinical approach in diagnostic radiology, although, at present, primarily in the area of detection of breast cancer in mammograms. Currently, a large research effort has been devoted to the detection and classification of various lung diseases in thoracic computed tomography (CT) images. We describe in this article the current status of the development of CAD schemes in thoracic CT, including nodule detection, distinction between benign and malignant nodules, and detection, characterization, and differential diagnosis of diffuse lung disease. Observer performance studies indicate that these CAD schemes would be useful in clinical practice by providing radiologists with computer output as a "second opinion."

Humans↗

Pericostal tuberculosis diagnosed by fine needle aspiration biopsy: report of a case with a review of the literature.

We present an 81-year-old woman with pericostal tuberculosis, a rare disease recently, without a past history of pulmonary tuberculosis or tuberculous pleurisy. She developed a subcutaneous nodule on her right chest. She was suspected of skin tuberculosis after the confirmation of acid-fast bacilli in a fine needle aspiration material of the nodule. A tuberculin skin test was strongly positive. The nodule was resected, and preclusive antituberculosis chemotherapy with rifampicin and isoniazid was started. The histological findings included granulomatous changes, central necrosis and Langhans' giant cells. Mycobacterium tuberculosis was identified from a culture of the specimen. About six months after the operation, no erythema, nodule or abscess was observed. We first suspected that she had mammary carcinoma and therefore observed the nodules on the thorax; it is important to differentiate tuberculosis from neoplasms. We also reviewed 22 cases of pericostal tuberculosis in Japan reported in the 15 years from 1976 to 2002.

Aged↗

Dual regulatory pathways integrating the RcsC-RcsD-RcsB signalling system control enterohaemorrhagic Escherichia coli pathogenicity.

Bacterial pathogenesis is strictly regulated in response to changes in environmental conditions. A His-Asp phosphorelay system consisting of a sensor kinase and response regulator is used by Gram-positive and Gram-negative bacteria to control gene expression in response to environmental stimuli. We screened His-Asp phosphorelay systems for their effect on virulence expression in enterohaemorrhagic Escherichia coli (EHEC), and found rcsD or rcsB overexpression enhanced locus for enterocyte effacement (LEE) gene transcription and adherence to Caco-2 cells through transcriptional activation of the ler regulatory gene. An EHEC-specific regulator GrvA, encoded by ECs1274, was required for ler transcription activation by RcsB. Furthermore, GrvA activated ler transcription in E. coli K12. Stimulation of the RcsDCB regulatory system by RcsF overexpression slightly increased EspB expression in the wild type but not the ECs1274 mutant. However, EspB expression in an rcsB deletion mutant increased compared with wild type, suggesting that RcsB negatively regulates LEE gene expression and that active RcsB protein is present under normal growth conditions. Deletion of pchA, which encodes a positive regulator for ler, abolished the effect of the rcsB deletion, suggesting that pchA mediated the negative RcsB effect. pchA transcript levels decreased when RcsB expression increased. Thus, LEE gene transcription may be regulated by RcsB through two oppositely regulated O157-specific regulators, PchA and GrvA.

Adaptation, Physiological↗

Ordered progress of spermiogenesis to the fertilizable sperm of the medaka fish, Oryzias latipes, in cell culture.

Spermiogenesis is significant for producing sperm with equipment for achieving fertilization. Although multiple events occur in a particular order during spermiogenesis, it is unclear how the timing of those events is controlled. In the present study, we found that primary spermatocytes obtained from the spermatogenic testes of Oryzias latipes synchronously differentiated into sperm without contact with somatic cells in culture. Because those sperm can fertilize with mature eggs (Saiki et al., 1997), any events of spermiogenesis that are essential for achieving fertilization are completed in the in vitro spermiogenesis. In the in vitro spermiogenesis, the protamine gene expression was observed in the early period and mitochondrion localization was established in the same period. Those results suggest that both nuclear remodeling and organelle replacement begin in the early period of spermiogenesis. The cytoplasmic lobe was formed after the mitochondrion localization had been established. In most spermatids differentiated in cell culture, a flagellum began to elongate during the early period and continued to elongate up to 3 days. These results revealed the timings of the spermiogenetic events under the intrinsic control of the cultured spermatids toward the formation of fertilizable sperm in O. latipes.

Animals↗

Computer-aided detection of peripheral lung cancers missed at CT: ROC analyses without and with localization.

PURPOSE: To retrospectively evaluate whether a difference-image computer-aided detection (CAD) scheme can help radiologists detect peripheral lung cancers missed at low-dose computed tomography (CT). MATERIALS AND METHODS: Institutional review board approval and informed patient and observer consent were obtained. Seventeen patients (eight men and nine women; mean age, 60 years) with a missed peripheral lung cancer and 10 control subjects (five men and five women; mean age, 63 years) without cancer at low-dose CT were included in an observer study. Fourteen radiologists were divided into two groups on the basis of different image display formats: Six radiologists (group 1) reviewed CT scans with a multiformat display, and eight radiologists (group 2) reviewed images with a "stacked" cine-mode display. The radiologists, first without and then with the CAD scheme, indicated their confidence level regarding the presence (or absence) of cancer and the most likely position of a lesion on each CT scan. Receiver operating characteristic (ROC) curves were calculated without and with localization to evaluate the observers' performance. RESULTS: With the CAD scheme, the average area under the ROC curve improved from 0.763 to 0.854 for all radiologists (P = .002), from 0.757 to 0.862 for group 1 (P = .04), and from 0.768 to 0.848 for group 2 (P = .01). The average sensitivity in the detection of 17 cancers improved from 52% (124 of 238 observations) to 68% (163 of 238 observations) for all radiologists (P < .001), from 49% (50 of 102 observations) to 71% (72 of 102 observations) for group 1 (P = .02), and from 54% (74 of 136 observations) to 67% (91 of 136 observations) for group 2 (P = .006). The localization ROC curve also improved. CONCLUSION: Lung cancers missed at low-dose CT were very difficult to detect, even in an observer study. The use of CAD, however, can improve radiologists' performance in the detection of these subtle cancers.

Aged↗

Measurement of residual adenoma after transurethral resection of the prostate by transurethral enucleation technique.

OBJECTIVE: Transurethral resection of the prostate (TURP) leaves a lot of residual adenoma and has a high recurrence rate, but the residual adenoma weight has not been measured surgically. Using surgery we tried to measure the residual adenoma after TURP. MATERIAL AND METHODS: Total adenoma resection was performed via standard TURP in 64 cases with benign prostatic hyperplasia and the weight of the residual adenoma was measured by transurethral enucleation (TUE) of the prostate. RESULTS: Prostate volume averaged 37.4 ml and adenoma volume averaged 20.6 ml by TRUS. The average weight of the prostate removed by TURP was 9.8 g. After TURP residual adenoma was confirmed in all cases by TUE, and the average weight of the residual adenoma was 10.2 g. The total average prostate volume removed by TURP and TUE was 20.1 g. The average residual rate of the adenoma removed by TURP was 54.5%. CONCLUSION: TURP leaves about half of the adenoma. Therefore, TURP might be very difficult for complete resection of an adenoma.

Aged↗

Effects of serum deprivation on expression of proteolytic-related genes in chick myotube cultures.

We previously reported that serum deprivation stimulates myofibrillar proteolysis in chick myotubes. In the present study, we examined the effect of serum deprivation on expression of the proteolytic-related genes (ubiquitin, proteasome, calpains, and cathepsin B) by real-time PCR of cDNA in chick myotubes. Myotubes were incubated with serum-free medium for 24 h. Ubiquitin and proteasome subunits (C1 and C2) and calpains (m-, mu-, and p94/calpain-3) but not cathepsin B mRNA expression were increased by serum deprivation. These results indicate that serum deprivation stimulates ubiquitin-proteasome and calpain proteolytic pathways, resulting in an increase in myofibrillar proteolysis in chick myotubes.

Animals↗

Effects of fasting and refeeding on expression of proteolytic-related genes in skeletal muscle of chicks.

This experiment was conducted to study the effects of fasting and refeeding on proteolytic-related gene expression in skeletal muscles of chicks. Chicks were fasted for 24 h, and refed for 2 h. Plasma Ntau-methylhistidine concentration, as an index of myofibrillar protein degradation, was increased by fasting, and that increment was reduced by refeeding. We also examined the expression of the protease mRNAs (calpain, proteasome, cathepsin and caspase-3) by real-time PCR of cDNA in skeletal muscles of fasting and refeeding chicks. Calpain (m-, mu-, and p94/calpain-3) mRNA expressions were also increased by fasting, and their increment was reduced by refeeding. Ubiquitin and 20S proteasome alpha subunit (alpha6 and alpha7) mRNA expressions as well as cathepsin B, and caspase-3 mRNA expression were likewise increased by fasting, with their increment also reduced by refeeding. These results indicate that fasting stimulates proteolytic-related gene expression, resulting in an increase in myofibrillar protein degradation, and that refeeding suppresses proteolytic-related gene expression, resulting in a decrease in myofibrillar protein degradation in chicks.

Animals↗

Malignant versus benign nodules at CT screening for lung cancer: comparison of thin-section CT findings.

PURPOSE: To evaluate thin-section computed tomographic (CT) characteristics of malignant nodules on the basis of overall appearance (pure ground-glass opacity [GGO], mixed GGO, or solid opacity) in comparison with the appearance of benign nodules. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained. Follow-up diagnostic CT was performed in 747 suspicious pulmonary nodules detected at low-dose CT screening (17 892 examinations). Of 747 nodules, 222 were evaluated at thin-section CT (1-mm collimation), which included 59 cancers and 163 benign nodules (3-20 mm). Thin-section CT findings of malignant versus benign nodules with pure GGO (17 vs 12 lesions), mixed GGO (27 vs 29 lesions), or solid opacity (15 vs 122 lesions) were analyzed. Fisher exact test for independence was used to compare differences in shape, margin, and internal features between benign and malignant nodules. Positive predictive value (PPV) was analyzed when a category was significantly different from the others. RESULTS: Among nodules with pure GGO, a round shape was found more frequently in malignant lesions (11 of 17, 65%) than in benign lesions (two of 12, 17%; P = .02; PPV, 85%); mixed GGO, a subtype with GGO in the periphery and a high-attenuation zone in the center, was seen much more often in malignant lesions (11 of 27, 41%) than in benign lesions (two of 29, 7%; P = .004; PPV, 85%). Among solid nodules, a polygonal shape or a smooth or somewhat smooth margin was present less frequently in malignant than in benign lesions (polygonal shape: 7% vs 38%, P = .02; smooth or somewhat smooth margin: 0% vs 63%, P < .001), and 98% (46 of 47) of polygonal nodules and 100% (77 of 77) of nodules with a smooth or somewhat smooth margin were benign. CONCLUSION: Recognition of certain characteristics at thin-section CT can be helpful in differentiating small malignant nodules from benign nodules.

Adenocarcinoma↗