Biomedical subjects

K Ohshima

Publications and source records attributed to K Ohshima.

At least 19 recordsLinked to original sources

PubMed2006

The variable codons of H3 influenza A virus haemagglutinin genes.

We have analyzed several sets of well-studied haemagglutinin (HA) gene sequences of H3 subtype influenza A viruses to identify codons that are unusually variable, using a simple pairwise sliding window method, DnDscanning. For two of the sets there were results of detailed phylogenetic modeling studies of selection already published. A third set had been the subject of an antigen mapping study, the results of which provide a completely independent benchmark of selected changes in H3 HA genes. Our analyses show that the codons with greatest DnDscan scores (i.e. the most variable) were mostly those reported in the published studies as being positively selected; indeed the DnDscan results matched the antigenic mapping results more closely than did those of the phylogenetic modeling methods. These results suggest that codons under selection can be found even when, as with some sets of virus sequences, a phylogeny is uncertain or cannot be obtained because, for example, the sequences are recombinants, or when selection is not necessarily linked with phylogeny, as in host-switching events. The program DnDscan is available at (biojanus.anu.edu.au).

Algorithms↗

PubMed2006

Expression of chemokines and chemokine receptors in cutaneous CD30+ lymphoproliferative disorders.

BACKGROUND: Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. OBJECTIVES: To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES. METHODS: Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30. RESULTS: CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder. CONCLUSIONS: We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.

Adolescent↗

PubMed2005

Gene expression profile of cytokines and chemokines in microdissected primary Hodgkin and Reed-Sternberg (HRS) cells: high expression of interleukin-11 receptor alpha.

We microdissected Hodgkin and Reed-Sternberg (HRS) cells from 14 Hodgkin's lymphoma tissue samples (nodular sclerosis = 5; mixed cellularity = 9), and after isolation and amplification of mRNA, analyzed the expression profile of 140 genes of chemokines, cytokines and their receptors by cDNA microarray methods. We also compared the profile with those of germinal center (GC) cells in reactive lymphadenitis. Unsupervised clustering revealed a relatively homogeneous expression profile in HRS cells. HRS cells tended to express mainly Th2 T cell-associated molecules rather than those of Th1, compared with GC cells. Interleukin-11 receptor alpha (IL-11Ralpha), a previously unknown HRS cell-specific gene, was detected in addition to known genes. Immunohistochemical staining confirmed the expression of IL-11Ralpha at the protein level. In contrast, only few cases were positive for IL-11Ralpha in B cell lymphoma, diffuse large cell lymphoma and follicular lymphoma. This is the first analysis report of tissue HRS cells with cDNA microarray technique.

Adolescent↗

PubMed2005

Prognosis of HTLV-I-positive renal transplant recipients.

HTLV-I is the pathogen that causes adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). The rate of disease development is low and the latency time is a few decades. However, the possible influence of immunosuppression on this disease development is unclear. The purpose of this study was to investigate the risk of development of ATL and HAM among the large number of HTLV-I-positive renal transplant recipients in western Japan. In principle immunosuppressive drugs have the possibilities to accelerate ATL development but are thought to suppress HAM development. Of 120 renal transplant recipients, 10 HTLV-I-positive recipients were reviewed, none of whom developed ATL or HAM. There are 11,896 dialysis patients in Japan and 300 dialysis patients in Okinawa who are registered with the JOTN for cadaveric renal transplant. The numbers of HTLV-I-positive patients in these groups were 97 (0.82%) and 26 (8.67%), respectively. These numbers are thought to be sufficient for an HTLV-I-positive recipient pool for HTLV-I-positive donors. Ten cases of ATL development and two of HAM development have been previously reported. Because of low number of ATL development, renal transplantation does not appear to be a contraindication for HTLV-I-positive chronic renal failure patients. In other words, kidneys from HTLV-I carriers, which include cadaveric donors, could be used for HTLV-I-positive recipients.

Adult↗

PubMed2005

Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances.

Follicular lymphomas (FL) are morphologically classified into grades 1, 2, 3a and 3b by the World Health Organization. Bcl2, Bcl6 and CD10 are phenotypic markers of FL while the Bcl2 t(14;18) and Bcl6 t(3q27) gene translocations are common genetic changes. However, to date, there has been no integrated analysis based on phenotype, grade and genotype from large numbers of FL cases. We graded 261 cases of FL and determined their phenotypes and gene alterations. According to the antigen markers and gene alterations of 147 cases, we classified FL into typical and the others types. The typical group, which includes 69% cases of FL, is characterized by low histological grade (grade 1, 2), coexpression of BCL2 and CD10 and Bcl2 gene translocation. The rest comprises a small part of low-grade FL without Bcl2 gene translocation and high-grade (grade 3a, 3b) FL. These FLs include some heterogeneous disease entities. They are characterized by high histological grade (87%), no definite expression of BCL2 or CD10 and several kinds of gene aberrances including Bcl2 translocation, Bcl6 translocation, Bcl2 amplification or other unknown gene abnormality. Our findings indicate that typical FL presents a homogeneous disease entity whereas the rest comprises heterogeneous diseases entities.

Biomarkers, Tumor↗

PubMed2005

Efficient engraftment of primary adult T-cell leukemia cells in newborn NOD/SCID/beta2-microglobulin(null) mice.

Adult T-cell leukemia (ATL) develops via multiple oncogenic steps in human T-cell leukemia virus type I (HTLV-I) carriers. To better understand pathogenesis of ATL, we developed a novel xenogeneic engraftment model in which primary ATL cells are intravenously transplanted into neonatal nonobese diabetic (NOD)/severe-combined immunodeficiency (SCID)/beta2-microglobulin(null) (NOD/SCID/beta2m(null)) mice. Acute-type ATL cells engrafted in the peripheral blood and in the lymph nodes of recipients at a high efficiency. Engrafted ATL cells were dually positive for human CD4 and CD25, and displayed patterns of HTLV-I integration identical to those of donors by Southern blot analysis. These cells infiltrated into recipients' liver, and formed nodular lesions, recapitulating the clinical feature of each patient. In contrast, in smoldering-type ATL cases, multiple clones of ATL cells engrafted efficiently in NOD/SCID/beta2m(null) mice. When smoldering-type ATL cells were retransplanted into secondary NOD/SCID/beta2m(null) recipients, single HTLV-I-infected clones became predominant, suggesting that clones with dominant proliferative activity can be competitively selected in this xenogeneic system. Taken together, the NOD/SCID/beta2m(null) newborn system is useful to understand kinetics, metastasis, and disease progression of ATL in vivo.

Anemia, Refractory, with Excess of Blasts↗

PubMed2005

FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma.

FOXP3 is a forkhead transcription factor family member, implicated in T-cell regulation, activation and differentiation. FOXP3 has been shown to be a master control gene for the development and function of CD4+/CD25+ regulatory T-cells (T(reg)). In this study, FOXP3 protein expression has been analysed using a new anti-FOXP3 monoclonal antibody in 172 paraffin-embedded lymphoma samples. FOXP3 expression in tumour cells was confined to adult T-cell leukaemia/lymphoma (ATLL) cases (17/25, 68%), with some variability in the intensity of the staining and the proportion of positive cells. No other lymphoma types studied exhibited FOXP3 expression in the malignant population. The selective expression of FOXP3 by tumour cells in ATLL makes this antibody a potentially useful diagnostic tool.

Antibodies, Monoclonal↗

PubMed2005

Clinicopathological features of cutaneous lesions of adult T-cell leukaemia/ lymphoma.

BACKGROUND: Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). ATLL frequently involves the skin. OBJECTIVES: To correlate the clinicopathological features and prognosis in patients with ATLL and cutaneous lesions. METHODS: We examined the HTLV-I proviral state and the clinicopathological features of the cutaneous lesions in 80 patients with serum anti-ATL antibody, to clarify the correlation between macroscopic/histopathological findings and prognosis. Southern blot analysis was performed in all cases to detect monoclonal HTLV-I proviral DNA integration. RESULTS: The cutaneous lesions of 46 patients were positive for proviral DNA integration. The median survival time of patients with monoclonal proviral DNA integration in cutaneous lesions was 14 months, which was markedly shorter than that of patients negative for proviral DNA integration (72 months). Of the 46 patients with proviral DNA, 21 had solitary or multiple red nodules (including three with subcutaneous induration), eight had multiple red papules and 17 had erythema. Patients with papules and nodules had poorer prognosis than those with erythema. Histopathologically, the prognosis was poorer in patients with nodular or diffuse infiltration of medium-sized to large lymphoma cells, compared with those with perivascular infiltration of small to medium-sized lymphoma cells. CONCLUSIONS: Our results show a close correlation between clinicopathological features of HTLV-I-associated cutaneous lesions and prognosis.

Adult↗

PubMed2005

Lymphomatous polyposis of the gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma.

AIMS: Lymphomatous polyposis (LP) is considered to represent mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract. However, a few reports have suggested that some are follicular lymphoma (FL) or mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we analysed 35 patients and clarified the clinicopathological features of LP. METHODS AND RESULTS: Paraffin-embedded tissue samples were stained immunohistochemically and analysed by tissue-fluorescence in situ hybridization (T-FISH) for IGH/CCND1 (cyclin D1) and IGH/BCL2. The average age of the patients was 58.3 years. Over half of the cases showed gastric, duodenal, small intestinal, ileocaecal and sigmoid colonic lesions (15, 19, 15, 16 and 16 cases, respectively). Phenotypically, cases were classified into three types of MCL (cyclin D1+ CD5+ CD10-) (n=12), FL (cyclin D1- CD5- CD10+) (n=14) and MALT (cyclin D1- CD5- CD10-) (n=9). T-FISH identified 11 of the 11 examined cases with MCLs to have IGH/CCND1, while seven of 10 cases with FL had IGH/BCL2, and none of the MALT cases were positive for IGH/CCND1 or IGH/BCL2. At the study endpoint, five of 12 patients with MCL were dead, two of 14 with FL and one of nine with MALT were dead of other disease. Event-free survival analysis showed significantly poorest outcome in MCL, followed by FL, while MALT was associated with a favourable outcome (P=0.0040). CONCLUSIONS: Our study emphasizes the importance of differentiating MCL, FL and MALT of LP in evaluating prognosis and hence the most suitable therapeutic regimen.

Aged↗

PubMed2005

SINEs and LINEs: symbionts of eukaryotic genomes with a common tail.

Many SINEs and LINEs have been characterized to date, and examples of the SINE and LINE pair that have the same 3' end sequence have also increased. We report the phylogenetic relationships of nearly all known LINEs from which SINEs are derived, including a new example of a SINE/LINE pair identified in the salmon genome. We also use several biological examples to discuss the impact and significance of SINEs and LINEs in the evolution of vertebrate genomes.

Animals↗

PubMed2004

Prognostic significance of hepatocyte growth factor and c-MET expression in patients with diffuse large B-cell lymphoma.

The expression and prognostic significance of hepatocyte growth factor (HGF) and its receptor c-MET (MET proto-oncogene) was analysed in 96 cases of diffuse large B-cell lymphoma (DLBCL). Tissue sections were immunohistochemically stained for HGF and c-Met. The prognosis of HGF-positive and c-Met-positive cases was significantly worse than negative cases (HGF: P = 0.0036; c-Met: P = 0.0002). In addition, in the low-risk international prognostic index group, HGF-negative and c-Met-negative cases had a significantly better prognosis than positive cases (HGF: P = 0.0009; c-Met: P < 0.0001). Our results suggest that HGF/c-MET is a useful clinical marker of prognosis for patients with DLBCL.

Adolescent↗

PubMed2004

Microarray analysis of human milk cells: persistent high expression of osteopontin during the lactation period.

To continue the search for immunological roles of breast milk, cDNA microarray analysis on cytokines and growth factors was performed for human milk cells. Among the 240 cytokine-related genes, osteopontin (OPN) gene ranked top of the expression. Real-time PCR revealed that the OPN mRNA levels in colostrum cells were approximately 100 times higher than those in PHA-stimulated peripheral blood mononuclear cells (PBMNCs), and 10 000 times higher than those in PB CD14(+) cells. The median levels of OPN mRNA in early milk or mature milk cells were more than three times higher than those in colostrum cells. Western blot analysis of human milk showed appreciable expression of full-length and short form proteins of OPN. The concentrations of full-length OPN in early milk or mature milk whey continued to be higher than those in colostrum whey and plasma as assessed by ELISA. The early milk (3-7 days postpartum) contained the highest concentrations of OPN protein, while the late mature milk cells (1 years postpartum) had the highest expression of OPN mRNA of all the lactating periods. The results of immunohistochemical and immunocytochemical staining indicated that OPN-producing epithelial cells and macrophages are found in actively lactating mammary glands. These results suggest that the persistently and extraordinarily high expression of OPN in human milk cells plays a potential role in the immunological development of breast-fed infants.

Blotting, Western↗

PubMed2003

Hemodynamic response of ovarian artery after hCG injection.

We have analyzed ovarian hemodynamics immediately after human chorionic gonadotropin (hCG) administration in patients treated by clomiphene-hCG and human menopausal gonadotropin-hCG. This study involved 40 infertile women who signed consents to participate in this study. After intramuscular injection of 10000 IU hCG, the change of ovarian arterial blood flow (BF) was evaluated by color Doppler. Pulsatility index, resistance index, maximum velocity (V(max)), mean velocity, minimum velocity, cross-sectional area of ovarian artery (Area) and BF were measured before and 15-180 min after hCG administration. In the 36 subjects in which ovulation was induced successfully, V(max) and BF increased significantly even at 15 min after hCG administration and thereafter. In the 4 non-ovulatory subjects, no significant changes in any of indices at any of measured time points were observed. Comparative study of non-ovulatory and ovulatory subjects suggested that ovulation may be predicted by the ovarian hemodynamic analysis immediately after hCG administration.

Adult↗

PubMed2003

Clinicopathological analysis of 143 primary malignant lymphomas in the small and large intestines based on the new WHO classification.

AIM: To study the clinicopathological and immunohistochemical features of 143 cases of primary small and large intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients who presented between 1981 and 2000. METHODS AND RESULTS: The new World Health Organization (WHO) classification was used to classify NHL. The patients included 109 males and 34 females, with an average age of 54.1 years. Tumour sites were as follows: ileocaecal (n = 51, 35.7%), ileum (n = 29, 20.3%), rectum (n = 13, 9.1%), and duodenum (n = 11, 7.7%). Macroscopically, 124 cases (86.7%) were classified as tumorous type, 12 (8.4%) as diffuse infiltration type (erosion, superficial ulceration), five (3.5%) as polyposis type, and only two cases (1.4%) as ulceration type. Immunohistochemically, 122 lesions (85.3%) were of B-cell phenotype and 21 lesions (14.7%) were of T-cell phenotype. According to the WHO classification, of the B-cell lymphomas, 84 cases (68.9%) were large cell, 16 (13.1%) were Burkitt, 10 (8.2%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), and seven (5.7%) were mantle cell tumours. Among the T-cell lymphomas, 15 (71.4%) were of unspecified type, two (9.5%) were natural killer type, two were anaplastic large-cell lymphomas, one was lymphoblastic, and one was an adult T-cell leukaemia lymphoma. The survival rate for T-cell lymphomas was poorer than for B-cell lymphomas. Among the B-cell lymphomas, mantle cell lymphoma tended to have a poorer prognosis, whereas MALT lymphomas had a better prognosis than other B-cell tumour types. CONCLUSIONS: Our retrospective study of patients with primary malignant lymphomas in the small and large intestines has illustrated the clinical features and outcomes of patients with this disease.

Adolescent↗

PubMed2003

The phylogeny of Turnip mosaic virus; comparisons of 38 genomic sequences reveal a Eurasian origin and a recent 'emergence' in east Asia.

The genomes of a representative world-wide collection of 32 Turnip mosaic virus (TuMV) isolates were sequenced and these, together with six previously reported sequences, were analysed. At least one-fifth of the sequences were recombinant. In phylogenetic analyses, using genomic sequences of Japanese yam mosaic virus as an outgroup, the TuMV sequences that did not show clear recombination formed a monophyletic group with four well-supported lineages. These groupings correlated with differences in pathogenicity and provenance; the sister group to all others was of Eurasian B-strain isolates from nonbrassicas, and probably represents the ancestral TuMV population, and the most recently 'emerged' branch of the population was probably that of the BR-strain isolates found only in east Asia. Eight isolates, all from east Asia, were clear recombinants, probably the progeny of recent recombination events, whereas a similar number, from other parts of the world, were seemingly older recombinants. This difference indicates that the presence of clear recombinants in a subpopulation may be a molecular signature of a recent 'emergence'.

Amino Acid Sequence↗

PubMed2003

Detection of interferon-gamma-inducible chemokines in human milk.

AIM: To assess the immunological role of human milk by analysing the concentrations of interferon-gamma-inducible protein of 10 kda (IP-10) and monokine induced by interferon-gamma (MIG) in human milk from mothers of preterm and term infants. METHODS: IP-10 and MIG levels of colostrum, early milk, mature milk and sera were measured by enzyme-linked immunosorbent assay (ELISA). IP-10 and MIG mRNA expression levels in cellular components of human milk were determined by RT-PCR. IP-10 and MIG protein expression in mammary gland tissues was analysed by immunohistochemistry. RESULTS: Significant amounts of IP-10 and MIG were detected in human milk. The concentrations of IP-10 and MIG in colostrum and early milk were significantly higher than those of sera from healthy controls or lactating mothers. These chemokine concentrations in colostrum and early milk were significantly higher than those of mature milk. Premature delivery or pregnancy complications of mothers had no significant correlation with these chemokine concentrations in breast milk. There were significant correlations between MIG and interferon-gamma (IFN-gamma) or IP-10 levels (p < 0.001) in human milk. Expression of IP-10 and MIG genes and proteins in the milk cells as well as in mammary gland epithelial tissues was detected by RT-PCR and immunohistochemistry. CONCLUSION: IP-10 and MIG in human milk, probably derived from milk cells and mammary gland epithelial cells, may contribute to the migration and activation of intestinal T lymphocytes to enhance mucosal immunity during the early neonatal period.

Adult↗

PubMed2003

Imbalance between apoptosis and telomerase activity in myelodysplastic syndromes: possible role in ineffective hemopoiesis.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. The heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is involved in pre-mRNA processing and binds to telomeric cDNA repeats. The hnRNP B1 is a marker for early cancer. The aim of our study was to clarify the relationships between prognosis and apoptosis, telomerase activity (TA) and hnRNP expression in the bone marrow. The subjects were 51 patients with MDS, including patients with refractory anemia (RA) (n = 32), refractory anemia with ringed sideroblasts (RARS) (n = 1), refractory anemia with excess blasts (RAEB) (n = 7), refractory anemia with excess blasts in transformation (RAEB-t) (n = 8) and chronic myelomonocytic leukemia (CMMoL) (n = 3). We also studied 6 cases with acute myelogenous leukemia (AML) arising from MDS (AML-MDS) and 10 control subjects. Bone marrow biopsies were stained immunohistochemically for caspase-3 (marker of apoptotic activity) and human telomerase reverse transcriptase (hTERT), and hnRNP B1. Fatal pancytopenia was the cause of death in 19 of the 51 patients. The caspase-3 positive cell rate was higher in MDS (16.3%) than in controls (4.4%) and AML-MDS (0.5%). The percentage of hnRNP B1-positive cells was higher in MDS (15.3%) and AML-MDS (56.3%) than in controls (5.6%). In MDS, hnRNP B1 levels were higher in RAEB and RAEB-t subtypes than in RA and RARS. The percentage of hTERT-positive cells was higher in AML-MDS (50.0%) than in controls (20.2%) and MDS (23.6%). Our findings suggest that activation of apoptosis occurs in MDS in the absence of hTERT expression, implicating high apoptosis in the absence of high TA with ineffective hematopoiesis. Poor prognosis correlated with higher caspase-3 and lower hTERT rates. In MDS, hnRNP B1 activity may be associated with leukemic transformation.

Adolescent↗

PubMed2002

Immunohistochemical detection of chemokines in human skin wounds and its application to wound age determination.

Immunohistochemical studies on the time-dependent expression of the chemokines such as interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha were performed on 50 human skin wounds with different wound ages (group I 0-12 h, group II 1-4 days, group III 7-14 days and group IV 17-21 days). In the wound specimens with wound ages between 4 and 12 h, neutrophils mainly showed positive reactions for IL-8, MCP-1 and MIP-1alpha. With increasing wound ages, macrophages and fibroblasts were positively stained with anti-IL-8, MIP-1alpha and MCP-1 antibodies. Morphometrically, there was a similar distribution in the positive ratios of the inflammatory cells among IL-8, MCP-1 and MIP-alpha. The positive ratios of each chemokine were very low in group I and a considerable increase of the positive ratios in each chemokine was observed in group II (mean +/- standard error IL-8: 59.8 +/- 2.1%, MCP-1: 42.4 +/- 3.1% and MIP-1alpha: 50.4 +/- 3.7%). Although the positive ratios for each chemokine gradually decreased according to the wound age, the mean positive ratios in groups III and IV were significantly higher than those in group I. From the forensic aspect, these chemokines are considered useful markers for wound age determination. Thus, ratios of > 50% for IL-8, > 30% for MCP-1 or > 40% for MIP-1alpha indicate a wound age of at least I day. Moreover, the combined investigation of these three chemokines can make wound age determination more objective and accurate.

Adolescent↗