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Biomedical subjects

R Abe

Publications and source records attributed to R Abe.

At least 127 records · Page 7Linked to original sources
PubMed1997

Increased secretion of TNF-alpha by costimulation of mast cells via CD28 and Fc epsilon RI.

The present study unequivocally demonstrated the expression of CD28 on murine bone marrow-derived cultured mast cells and a mast cell line, MCP-5. Stimulation of surface CD28 molecules on mast cells with anti-CD28 mAbs induced tyrosine phosphorylation of cellular proteins, including several protein tyrosine kinases and their substrates, such as Itk/Emt (Emt), Btk, Syk, c-Cbl, Shc, and Vav. CD28-stimulated tyrosine phosphorylation was followed by a rebound hypophosphorylation. Interestingly, CD28 stimulation alone elicited a low level secretion of TNF-alpha. On the other hand, cross-linking of the high affinity IgE receptor (Fc epsilon RI) on mast cells induces a set of activation events, i.e., degranulation, secretion of eicosanoids, secretion of cytokines, and DNA synthesis. Concurrent stimulation of mast cells through CD28 enhanced Fc epsilon RI-induced TNF-alpha secretion in a dose-dependent manner. Together, the present data suggest a role for CD28-mediated costimulation of mast cells in the initiation and progression of allergic responses and other diseases.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1997

Role of age as a prognostic factor in breast cancer.

The effect of age on the prognosis of breast cancer remains controversial. To investigate the role of age, we reviewed 316 patients with stage I or II breast cancer. There were 14 patients below 34, 146 between 35 and 49, 115 between 50 and 65, and 41 over 66 years of age. No correlations were observed between age and clinicopathological variables. Breast cancer patients aged 34 or less had a significantly worse survival compared to those in the older age groups. Multivariate analysis also showed younger age to be a significant factor, followed by lymph node status. Therefore, younger age at onset is considered to be an independent prognostic factor.

Adult↗
PubMed1997

The impact of lymph node metastases on the survival of breast cancer patients with ten or more positive lymph nodes.

To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10-15 nodes, or the 11 with 16-25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%-75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with < 50% or > 75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.

Adult↗
PubMed1997

Synergy between CD28 and CD9 costimulation for naive T-cell activation.

Our previous study demonstrated that CD9 is expressed on most mature naive T-cells and delivers a potent costimulatory signal that functions independently of CD28. Here, we investigated whether this CD9-mediated signal is different from the CD28-mediated signal in the mode of costimulation and whether both signals function synergistically for T-cell activation. Anti-CD9 or anti-CD28 monoclonal antibody (mAb) increased [3H]TdR incorporation of naive T-cells in the absence of antigen-presenting cells (APC) when coimmobilized with submitogenic doses of anti-CD3 mAb. The levels of costimulation induced by ligation of CD9 and CD28 were comparable. However, the costimulatory effect differed between soluble anti-CD9 and CD28 mAb. A soluble form of anti-CD28 mAb could costimulate anti-CD3-triggered T-cells, whereas soluble anti-CD9 mAb failed to costimulate. Although anti-CD28 costimulated naive T-cells treated with phorbol myristate acetate (PMA) instead of anti-CD3 mAb, a combination of PMA plus anti-CD9 mAb could not induce T-cell activation. The combined costimulation of anti-CD3-triggered T-cells with anti-CD9 and anti-CD28 mAbs resulted in strikingly enhanced [3H]TdR uptake and lymphokine (IL-2 and IFN-gamma) production when compared to those induced by each costimulation. These results suggest that CD9 and CD28 induce T-cell costimulation using different signaling pathways, thereby inducing synergy in T-cell activation.

Animals↗
PubMed1997

Chronic myelogenous leukemia with a hypooctoploid cell population.

A patient with chronic myelogenous leukemia who underwent transformation from the accelerated phase to the chronic phase with interferon-alpha treatment is reported. On admission, the numbers of myeloblasts and promyelocytes in the peripheral blood and bone marrow were 7.0% and 12.8%, respectively. The platelet count was 633.6 x 10(4)/microliter, and megakaryocytes were frequent in the bone marrow. In the accelerated phase, cytogenetic analyses revealed a hypotetraploid and a hypooctoploid cell population with two and four Philadelphia chromosomes, respectively, in the bone marrow specimen. The hypooctoploid clone disappeared with administration of interferon-alpha and the hypotetraploid clone also subsequently disappeared.

Aged↗
PubMed1997

A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development.

Development of immature CD4+ CD8+ thymocytes into functionally mature CD4+ and CD8+ T cells is driven by selection events that require signals transduced through the T cell antigen receptor (TCR). Transduction of TCR signals in the thymus involves tyrosine phosphorylation of the protein tyrosine kinase ZAP-70 by p56(lck) and results in induction of ZAP-70 enzymatic activity. We have identified a novel, spontaneously arising point mutation within a highly conserved motif (DLAARN) in the kinase domain of murine ZAP-70 that uncouples tyrosine phosphorylation of ZAP-70 from induction of ZAP-70 kinase activity. Mice homozygous for this mutation are devoid of mature T cells because thymocyte development is arrested at the CD4+ CD8+ stage of differentiation. The developmental arrest is due to the inability of CD4+ CD8+ thymocytes to propagate TCR signals in the absence of ZAP-70 kinase activity despite tyrosine phosphorylation of TCR-associated ZAP-70 molecules.

Amino Acid Sequence↗
PubMed1997

Clinical significance of tissue inhibitor of metalloproteinase expression in gastric carcinoma.

Tissue inhibitor of metalloproteinase (TIMP) has been reported to inhibit tumour invasion through an inactivation of matrix metalloproteinase (MMP) both in vitro and in vivo. Among the TIMP family, TIMP-1 possesses not only proteinase inhibitory activity but also a growth-promoting function. However, the significance of the expression of TIMP-1 in human gastric carcinoma tissue has yet to be clarified. In 50 examined cases of gastric carcinoma, 44 (88%) cases showed a higher expression of TIMP-1 mRNA in the biopsy samples from the tumour tissue (T) than in the biopsy samples from the corresponding normal tissue (N), as determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In a multivariate analysis, the T/N ratio of TIMP-1 mRNA was found to be an independent factor influencing the depth of tumour invasion and was the second most important factor in determining the prognosis of patients. As RT-PCR assay can be performed on biopsy specimens obtained before surgery, an evaluation of the TIMP-1 expression in biopsy specimens by RT-PCR may thus provide useful preoperative information on tumour aggressiveness.

Adult↗
PubMed1997

Effective high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in a patient with the aggressive form of cytophagic histiocytic panniculitis.

A 20-year-old Japanese man developed generalized, subcutaneous, painless nodules, fever, abnormal liver function, serosal effusions, hepatosplenomegaly, lymphadenopathy and anemia. Skin biopsies revealed lobular panniculitis with a morphologically benign histiocytic infiltration and prominent phagocytosis. Atypical T lymphocytes were also present in the skin and liver. The diagnosis given was aggressive cytophagic histiocytic panniculitis (CHP) or aggressive subcutaneous panniculitic T cell lymphoma (SPTCL). He received cyclophosphamide, doxorubicin, and vincristine on day 1, prednisolone on days 1-5, and etoposide on days 1, 3 and 5 (CHOP-E), with the support of granulocyte colony-stimulating factor. This regimen was repeated every 2 weeks and complete clinical remission (CCR) was attained after three cycles of CHOP-E. As the clinical course of aggressive CHP is recurrent and often fatal, he was given high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT), after five cycles of CHOP-E. He has remained in CCR for 12 months after APBSCT. High-dose chemotherapy followed by APBSCT is considered to be one of the most beneficial therapies for patients with aggressive CHP and aggressive phase SPTCL.

Adolescent↗
PubMed1997

Mitogenic stimulation of T cells reveals differing contributions for B7-1 (CD80) and B7-2 (CD86) costimulation.

The requirement of accessory cells for concanavalin A (Con A) activation of T cells suggests delivery of a separate costimulatory signal. However, the costimulatory pathways involved have not been identified. These studies assess the role of CD28-B7-mediated costimulation during T-cell activation by Con A. The B7-1/B7-2 binding protein CTLA4-Ig inhibited the proliferative response of primary lymph node cells to either Con A or soluble anti-CD3 mAb. This suppression was dose dependent and could be reversed by CD28 cross-linking. CTLA4-Ig also completely suppressed induction of interleukin-2 (IL-2) mRNA by Con A. CTLA4-Ig-mediated suppression was not due to blockade of the Con A 'receptor(s)' or of the primary activation signal (as measured by the intracellular calcium response). Although both B7-1 and B7-2 were up-regulated following Con A activation, each played a different role in proliferation and cytokine production. Individually, anti-B7-2 Fab partially inhibited the Con A response whereas anti-B7-1 Fab had no effect. However, the combination of anti-B7-1 and anti-B7-2 Fab completely suppressed proliferation and IL-2 production. Therefore, while a part of the Con A response requires B7-2, the remainder of the response can utilize either B7-1 or B7-2. Together, these results demonstrate that Con A activation of T cells requires the delivery of a separate costimulatory signal that is mediated almost entirely by the B7 receptors.

Animals↗
PubMed1997

[Measurement of relative plasma volume and plasma refilling rate during ultrafiltration of hemodialysis by measuring apparatus of plasma colloidal osmotic pressure].

BACKGROUND: The objective of this study is the prevention of unexpected hypotension during hemodialysis caused by unsuitable filtration rate. METHODS: The plasma colloidal osmotic pressure (COP) was measured continuously during ultra-filtration, and relative plasma volume (%PV) and plasma refilling rate (PRR) were calculated during 12 ECUMs and one dialysis on twelve patients in early stage of chronic renal failure. Values of %PV and PRR calculated from COP were drawn in graphic curves, and analysed to obtain characteristic pattern. Minimum value of %PV (%PV min), maximum value of PRR (PRRmax) and time for PRR to decrease to 95% (95% PVt) on the curves were documented simultaneously. RESULTS: At the initial stage of %PV curve, obvious fall was observed on 6 of 13 estimation (initial fall of %PV). On the contrary at the initial stage of PRR curve, obvious rise was observed on 5 estimation (initial rise of PRR). A close relationship was indicated between the two phenomenons. In 6 cases with initial fall of %PV and in 5 cases with initial rise of PRR body weight, PRRmax and 95%PVt were lower than another cases without it. The ultra-infiltration velocity was estimated to be relatively high in these groups. In these 8 cases, filtrated water volume was judged as adequate clinically. In 4 of 5 cases without final fall of PRR, it was judged as inadequate and needed to evacuate more 0.9 to 3.0 kg (average of 1.8 +/- 1.07) of water from the patients. CONCLUSIONS: From the above, we concluded that our method is useful for deciding suitable velocity of ultrafiltration and dry weight in hemodialysis therapy.)

Adult↗
PubMed1997

[Pulmonary aspergilloma with ring enhancement on chest CT scans].

A 77-year-old man with hemoptysis was admitted to our hospital. A coin lesion in the right middle lung field was observed on a chest X-ray film. Enhanced CT scans of the chest showed the coin lesion with clear ring enhancement. Ring-enhanced mass shadow in cases of pulmonary diseases are very rare. The level of anti-aspergillus antibody in serum was high and the patient was given the diagnosis of aspergillosis. An upper lobectomy was done and aspergillus organisms were found.

Aged↗
PubMed1997

Anaplastic carcinoma showing rhabdoid features combined with mucinous cystadenocarcinoma of the pancreas.

A 52-year-old Japanese woman presented with complaints of back pain, loss of appetite, and weight loss; her diagnosis was a mass in the pancreatic tail. A distal pancreatectomy combined with lymph node dissection was performed. The tumor measured 10.0 x 9.5 x 8.0 cm and consisted of a cystic mass and a solid area. Histologically, the cystic mass represented a typical mucinous cystadenocarcinoma, whereas the solid portion was composed of anaplastic tumor cells with round eosinophilic intracytoplasmic inclusions, as seen in malignant rhabdoid tumor of the kidney. The hyaline-like intracytoplasmic inclusions were weakly positive for periodic acid-Schiff and were resistant to diastase. There was a gradual transition between the mucinous cystadenocarcinoma and the anaplastic carcinoma showing rhabdoid features. Additionally, the tumor cells of the anaplastic carcinoma were immunoreactive to both epithelial membrane antigen and vimentin. These findings suggest that the anaplastic carcinoma with rhabdoid features developed from the mucinous cystadenocarcinoma of the pancreas.

Carcinoma↗
PubMed1997

K-ras and p53 gene mutations in colorectal cancer in 57 Japanese patients.

Fifty-eight tissue specimens from 57 Japanese patients with colorectal cancer were analyzed for the K-ras and p53 gene mutations by polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing. K-ras mutations were detected in 21 cases (36.2%) and p53 mutations in 20 cases (34.5%). Eight specimens had both gene mutations. The K-ras mutation was associated with higher degrees of differentiation (p = 0.0019). The P53 mutation was associated with Duke B to D staging (p = 0.028), lymph vessel invasion (p = 0.021), and venous invasion (p = 0.03). Interestingly, a mutation in only exon 7 of the P53 gene was associated with lymph node metastasis. These results suggest the important effect of the mutations of the K-ras and p53 genes, especially p53 gene on colorectal carcinogenesis in Japanese patients. The grades of malignancy of the specimens with the mutations in both genes were not different significantly from those with a single (K-ras or p53) or no mutation, suggesting no cooperation between K-ras and p53 gene mutations on carcinogenesis or tumorigenesis.

Adenocarcinoma↗
PubMed1997

Nuclear DNA content, S-phase fraction analysis and expression of proliferating cell nuclear antigen (PCNA) of normal and hyperplastic/neoplastic parathyroid glands.

To clarify the biological behavior, the flowcytometric nuclear DNA content, S-phase fraction(SPF) and proliferating cells by immunostaining of proliferating cell nuclear antigen(PCNA) were investigated in 13 patients with hyperparathyroidism (10 adenomas, 2 hyperplasias and 1 cancer) and 10 normal controls. No. of parathyroid glands or tissues examined was as follows: 10 adenomas, three hyperplasias from one case, one primary and one recurrent carcinoma of the same case, two secondary hyperplasias from one case and 10 normal glands. All controls and hyperplasias showed diploid DNA, but the 10 adenomas aneuploid in four and diploid in six. The carcinoma showed diploid in the primary lesion, aneuploid in the recurrence. DNA index in recurrent carcinoma was higher than that in aneuploid adenoma. SPF in primary and recurrent cancers and adenomas as higher than that in the others. The expression of PCNA in all hyperparathyroidism except for hyperplasias was higher than that in normal controls. In conclusion, there might be some premalignant potential in the adenomas from the view of DNA flowcytometry and PCNA immunostaining. Therefore, aneuploid adenoma should be strictly followed up.

Adenoma↗
PubMed1997

Correlation between the expression of apoptosis-related bcl-2 and p53 oncoproteins and the carcinogenesis and progression of breast carcinomas.

The proto-oncogene bcl-2, which is implicated in the regulation of cell death by inhibiting apoptosis, is reported to be expressed in breast tissues. The wild-type p53 has been shown to induce apoptosis, which can be inhibited by bcl-2 expression. However, the role of bcl-2 and p53 expression in breast carcinogenesis has not been clarified. The purpose of this study was to evaluate bcl-2 and p53 expression in normal breast epithelia cells, as well as in intraductal and invasive cancerous lesions of breast cancer tissue using an immunohistochemical method and to clarify their role in the development of breast cancer. The nuclear accumulation of p53 was also evaluated by quantitative image analysis. Expression of bcl-2 was found in 79 of 82 (96%) normal ductal epithelial cells, in 50 of 63 (79%) intraductal carcinomas, and in 62 of 137 (45%) invasive carcinomas, respectively. Higher bcl-2 expression was observed in normal epithelial cells than in intraductal and invasive cancerous cells (P < 0.0001). Furthermore, bcl-2 positivity in intraductal lesions was significantly higher than in invasive cancerous lesions (P < 0.05). No p53 nuclear accumulation was observed in normal breast epithelial cells. Fifteen of 63 (23.8%) intraductal cancerous lesions and 41 of 137 (30%) invasive cancerous lesions were positive for p53 expression. An inverse relationship was shown between bcl-2 and p53 expression in invasive carcinomas. We demonstrated that bcl-2 expression exists in most of normal ductal epithelial cells and gradually decreases during the development of breast cancer, i.e. , from a normal epithelium to intraductal carcinoma, and from intraductal to invasive carcinoma, and that p53 expression may occur early in breast cancer development and increases during progression.

Apoptosis↗
PubMed1996

Two different RNA binding activities for the AU-rich element and the poly(A) sequence of the mouse neuronal protein mHuC.

HuC is one of the RNA binding proteins which are suggested to play important roles in neuronal differentiation and maintenance. We cloned and sequenced cDNAs encoding a mouse protein which is homologous to human HuC (hHuC). The longest cDNA encodes a 367 amino acid protein with three RNA recognition motifs (RRMs) and displays 96% identity to hHuC. Northern blot analysis showed that two different mRNAs, of 5.3 and 4.3 kb, for mouse HuC (mHuC) are expressed specifically in brain tissue. Comparison of cDNA sequences with the corresponding genomic sequence revealed that alternative 3' splice site selection generates two closely related mHuC isoforms. Iterative in vitro RNA selection and binding analyses showed that both HuC isoforms can bind with almost identical specificity to sequences similar to the AU-rich element (ARE), which is involved in the regulation of mRNA stability. Functional domain mapping using mHuC deletion mutants showed that the first RRM binds to ARE, that the second RRM has no RNA binding activity by itself, but facilitates ARE binding by the first RRM and that the third RRM has specific binding activity for the poly(A) sequence.

Alternative Splicing↗