Successful treatment with combination therapy of cyclophosphamide and cyclosporin for late recurrence of Wegener granulomatosis.
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Adult↗
Biomedical subjects
M Inoue
Publications and source records attributed to M Inoue.
14-3-3tau associates with a translational control factor FKBP12-rapamycin-associated protein in T-cells after stimulation by pervanadate.
Proteins of the 14-3-3 family can associate with and/or modulate the activities of a variety of proteins, such as protooncogene and oncogene products, Cdc25 phosphatases and phosphatidylinositol 3-kinase, and thus are implicated in regulation of signaling pathways and the cell cycle. We report here that treatment of Jurkat T-cells with an inhibitor of protein tyrosine phosphatase, pervanadate, induces the association of 14-3-3tau with a translational control factor, FKBP12-rapamycin-associated protein (FRAP), with significant latter's autophosphorylation. Coimmunoprecipitation of various mutants of FRAP coexpressed with 14-3-3tau in COS-7 cells revealed that 14-3-3tau binds to the C-terminal side of FRAP at unknown site(s) different from the predicted binding motifs to date.
14-3-3 Proteins↗
Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT).
Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. The human telomerase catalytic subunit (hTERT) is a rate limiting determinant of the enzymatic activity of human telomerase. In the previous study, we identified the proximal 181 bp core promoter responsible for transcriptional activity of the hTERT gene. To identify the regulatory factors of transcription, transient expression assays were performed using hTERT promoter reporter plasmids. Serial deletion assays of the core promoter revealed that the 5'-region containing the E-box, which binds Myc/Max, as well as the 3'-region containing the GC-box, which binds Sp1, are essential for transactivation. The mutations introduced in the E-box or GC-box significantly decreased transcriptional activity of the promoter. Overexpression of Myc/Max or Sp1 led to significant activation of transcription in a cell type-specific manner, while Mad/Max introduction repressed it. However, the effects of Myc/Max on transactivation were marginal when Sp1 sites were mutated. Western blot analysis using various cell lines revealed a positive correlation between c-Myc and Sp1 expression and transcriptional activity of hTERT. Using fibroblast lineages in different stages of transformation, we found that c-Myc and Sp1 were induced to a dramatic extent when cells overcame replicative senescence and obtained immortal characteristics, in association with telomerase activation. These findings suggest that c-Myc and Sp1 cooperatively function as the major determinants of hTERT expression, and that the switching functions of Myc/Max and Mad/Max might also play roles in telomerase regulation.
Base Sequence↗
Neurofilament-L is a protein phosphatase-1-binding protein associated with neuronal plasma membrane and post-synaptic density.
Far Westerns with digoxigenin-conjugated protein phosphatase-1 (PP1) catalytic subunit identified PP1-binding proteins in extracts from bovine, rat, and human brain. A major 70-kDa PP1-binding protein was purified from bovine brain cortex plasma membranes, using affinity chromatography on the immobilized phosphatase inhibitor, microcystin-LR. Mixed peptide sequencing following cyanogen bromide digestion identified the 70-kDa membrane-bound PP1-binding protein as bovine neurofilament-L (NF-L). NF-L was the major PP1-binding protein in purified preparations of bovine spinal cord neurofilaments and the cytoskeletal compartment known as post-synaptic density, purified from rat brain cortex. Bovine neurofilaments, at nanomolar concentrations, inhibited the phosphorylase phosphatase activity of rabbit skeletal muscle PP1 catalytic subunit but not the activity of PP2A, another major serine/threonine phosphatase. PP1 binding to bovine NF-L was mapped to the head region. This was confirmed by both binding and inhibition of PP1 by recombinant human NF-L fragments. Together, these studies indicate that NF-L fulfills many of the biochemical criteria established for a PP1-targeting subunit and suggest that NF-L may target the functions of PP1 in membranes and cytoskeleton of mammalian neurons.
Amino Acid Sequence↗
Cell dynamics and expression of tumor necrosis factor (TNF)-alpha, interleukin-6, and TNF receptors in angioimmunoblastic lymphadenopathy-type T cell lymphoma.
Angioimmunoblastic lymphadenopathy (AILD)-type T cell lymphoma is histologically characterized by a mixed infiltrate of atypical T cells and B cells including B immunoblasts and plasma cells as well as eosinophils accompanied by proliferation of high endothelial venules. These morphological peculiarities are widely believed to reflect an abnormal pattern of cytokine expression. To clarify the cell dynamics and cytokine expression pattern in the lymph nodes of AILD-type T cell lymphoma, the frequency of proliferating/apoptotic cells and localization of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 producing cells were determined. Double staining was performed for (1) cell markers and Ki-67 antigen, (2) cell markers and the terminal deoxytransferase-mediated dUTP nick end labeling (TUNEL) method, or (3) cell markers and cytokines. The proliferating cell ratio in atypical T cells of AILD-type T cell lymphoma determined by Ki-67 labeling was 20.2+/-5.0%, while other peripheral T cell lymphomas (PTL) exhibited a ratio of 32.9+/-2.5%. TUNEL-positive apoptotic cells were 0.8+/-0.1% of total cells in AILD-type T cell lymphoma. They were dominantly atypical cells with positive T cell markers. In contrast, lymphoma cells in other types of PTL or paracortical cells in reactive follicular hyperplasia had only 0.3+/-0.1 or 0.4+/-0.1% TUNEL-positive cells, respectively. Thus, lymphoma cells in AILD-type T cell lymphoma demonstrated suppressed proliferating activity and enhanced apoptosis when compared to other types of PTL. TNF-alpha-producing cells were observed in all of the lymph nodes from AILD-type T cell lymphoma cases (15/15) and positive staining was obtained in the majority of atypical T cells and scattered macrophages. In contrast, IL-6 was localized to clusters of atypical T cells in some of the cases (9/15). Further, the expression of TNF-alpha, IL-6, and TNF receptors I and II (TNFRI and TNFRII) was examined by RT-PCR. The TNF-alpha message (2/2) and IL-6 message (2/2) was present in the lymph nodes of AILD-type T cell lymphoma by examination using RT-PCR, while both messages were negative in control cases (0/7). As far as an expression of mRNA for TNF receptors in AILD-type T cell lymphoma cases, mRNA for TNFRI was definitely expressed in both of the cases (2/2) while TNFRII mRNA was weakly expressed in one case (1/2). Overexpression of TNF-alpha as well as TNFRI may play a role in controlling T cell proliferation through an autocrine (T cell-T cell interaction) and paracrine (macrophage-T cell interaction) fashion. IL-6, which was also expressed by part of lymphoma cells of AILD-type T cell lymphoma, facilitates the proliferation of B cells, plasma cells, and T cells or endothelial cells in the lymph nodes of AILD-type T cell lymphoma.
Adult↗
A case of cervical cancer with aggressive tumor growth: possible autocrine growth stimulation by G-CSF and Il-6.
BACKGROUND: Patients with tumors that produce hematopoietic growth factors, such as G-CSF, sometimes exhibit leukemoid reactions. Squamous cell carcinomas of the uterine cervix producing such factors are rarely reported. CASE: A 56-year-old woman had severe leukocytosis (>50 x 10(3)/microl) and fever without evidence of infection after radical hysterectomy for treatment of her cervical cancer. The parametrial recurrent mass appeared after the operation and exhibited extremely aggressive growth. Serum levels of G-CSF and IL-6 were extremely high, and immunohistochemical analysis and RT-PCR assays revealed that G-CSF and IL-6 as well as their receptors were produced in tumor cells. CONCLUSIONS: This is a case of cervical cancer which exhibited an aggressive clinical course, possibly due to autocrine stimulation of cell growth by G-CSF and IL-6.
Carcinoma, Squamous Cell↗
Malignant struma ovarii with Graves' disease.
BACKGROUND: Malignant struma ovarii is a rare tumor, consisting of a struma ovarii with malignant change. Because of the rarity of the tumor, only a few reports with detailed data of thyroid function of the patient have been published. CASE: Medical and surgical treatments were performed in a case of malignant struma ovarii with Graves' disease and data from thyroid function tests were analyzed. After removal of the tumor, rapid improvement of thyroid function was observed and thyroglobulin level decreased. CONCLUSION: This case demonstrates the possible, if not dominant, contribution from the malignant struma ovarii to the hyperthyroidism of the patient.
Female↗
Synthesis of immunomodulatory marine natural products.
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Adjuvants, Immunologic↗
Optimal therapeutic range for oral anticoagulants in Japanese patients with prosthetic heart valves: a preliminary report from a single institution using conversion from thrombotest to PT-INR.
The thrombotest (TT) technique has been widely used in Japan for monitoring oral anticoagulant therapy (OAT). The therapeutic range was originally recommended to be 10%-25%. However, the International Committee for Standardization in Hematology/International Committee on Thrombosis and Hemostasis (ICSH/ICTH) recommended using the international normalized ratio of prothrombin time (PT-INR) for monitoring OAT. It is necessarv to use a universal standard measure for monitoring OAT in accordance with the ICSH/ISTH recommendation. We simultaneously measured TT and PT in blood samples from 1,157 patients on long-term warfarin therapy, and studied the correlation between TT and PT-INR. An excellent linear correlation was obtained between TT-INR and PT-INR with the regression equation PT-INR = 1.0420 TT-INR - 0.0987 (r = 0.905, P < 0.001). We also examined the correlation between the incidence of thromboembolism in 170 patients receiving warfarin therapy after prosthetic valve replacement; 50.5% received concomitant antiplatelet therapy. Thromboembolism occurred in 9 of 170 patients during a mean follow-up period of 2.44 years. The average TT values in patients with and without thromboembolism were 26.4% (PT-INR: 1.53) and 21.1% (1.73), respectively (P < 0.01). The incidence of thromboembolism did not differ significantly between patients on warfarin alone (average TT: 22.2%) and those on warfarin and antiplatelet agent (average TT: 20.9%). Our results suggest that the incidence of thromboembolism is low in Japan despite a less intensive regimen having been adopted.
Administration, Oral↗
The effects of body positioning on sucking behaviour in sick neonates.
UNLABELLED: Some infants show better oxygenation in the prone position compared to the supine position while they are bottle-fed; however, the reason for this phenomenon is not clear. The purpose of this study was to obtain a better understanding of the effects of body position on the oral feeding performance, i.e. the sucking pressure, frequency, efficiency, and ventilation. A total of 14 infants (12 full-term, 2 preterm), who often showed O2 desaturation (SpO2 < 90) during oral feeding, were enrolled in the study. The infants were fed either in the supine position or in the prone position throughout feeding. Oxygen saturation was recorded with a pulse oxymeter. The sucking pressure was measured with a 1 mm I.D. silicone tube inserted into the artificial nipple. The ventilation volume during bottle feeding was measured with a pneumotachograph. The prone position resulted in better oxygenation (97.2 +/- 0.6% prone, 92.5 +/- 0.9% supine, P < 0.05) and larger tidal volume (6.4 +/- 0.8 ml/kg prone and 4.9 +/- 0.6 ml/kg supine, P < 0.05), although the minute ventilation during bottle-feeding was not different from that in the supine position. In the prone position, the sucking pressure and frequency were higher and the duration of each suck was shorter. CONCLUSION: Sucking in the prone position may to some extent reduce disadvantages of oral feeding on ventilation.
Gestational Age↗
Preoperative intranasal mupirocin ointment significantly reduces postoperative infection with Staphylococcus aureus in patients undergoing upper gastrointestinal surgery.
Nasal carriage of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) is associated with an increased risk for postoperative staphylococcal infection. This study was conducted to investigate the effect of preoperative nasal mupirocin treatment on the postoperative infections in patients undergoing upper gastrointestinal surgery. The intervention group consisted of 141 consecutive patients who underwent upper gastrointestinal surgery between March 1, 1997, and February 28, 1998. The patients in the intervention group were treated with intranasal mupirocin three times a day for 3 consecutive days before surgery. The incidence of postoperative staphylococcal infections in the intervention group was then compared with that of the historical control group. The control group consisted of 128 consecutive patients who underwent upper gastrointestinal surgery without mupirocin treatment between January 1, 1996 and December 31, 1996. The postoperative staphylococcal infection rate in the control group (11.7%) was significantly higher (P < 0.001) than in the intervention group (0.71%). The postoperative MRSA infection rate was significantly reduced by the intervention (control group 7.0% and intervention group 0%; P < 0.01). These results suggest that preoperative nasal eradication of S. aureus with mupirocin thus appears to be an effective measure to prevent postoperative staphylococcal infection in patients undergoing upper gastrointestinal surgery.
Administration, Intranasal↗
Appraisal of treatment strategy by staging laparoscopy for locally advanced gastric cancer.
More accurate preoperative staging is necessary to determine the treatment strategy for locally advanced gastric cancer. Thirty-two patients with T3 or T4 gastric cancer expected to undergo curative resection based on conventional examinations underwent staging laparoscopy. The disease stages determined were compared with those obtained by conventional methods. The discrepancy rate of disease staging was 16 of 32 (50.0%), with down-staging in 5 of 32 (15.6%) and up-staging in 11 of 32 (34.4%). Of the 32 patients, 13 (40.6%) were found to have unsuspected peritoneal dissemination. The positive predictive value for peritoneal metastasis by staging laparoscopy was 100%, whereas the negative predictive value was 89% (17/19). The accuracy rate was 94%. After laparoscopy, 15 of the 32 (46.9%) were diagnosed as candidates for curative resection. Of these 15 patients who underwent surgery, 13 (86.7%) underwent curative resection (1 R0 and 12 R1); the remaining two underwent R2 resection because of peritoneal metastasis that was undetected by staging laparoscopy. Patients with tumors judged noncurable by laparoscopy (n = 11) received neoadjuvant chemotherapy. In 7 of the 11 cases, salvage surgery was done (one R0, three R1, three R2 resections). A second staging laparoscopy was performed in four cases to determine the indication for salvage surgery. Three of the four were judged to be curable and underwent curative resection. Staging laparoscopy is an effective tool for detecting unsuspected peritoneal metastasis, and it can increase the curative resection rate and decrease unnecessary laparotomy for advanced gastric cancer. Second-look laparoscopy enables accurate assessment of the chemotherapeutic response, which can help in decisions about salvage surgery.
Adenocarcinoma↗
Aciculin and its relation to dystrophin: immunocytochemical studies in human normal and Duchenne dystrophy quadriceps muscles.
Aciculin is a novel adherens junction antigen extracted from human uterine smooth muscle that is reported to associate biochemically with dystrophin. We attempted to determine (i) the immunostainability of anti-aciculin antibody for the 6 histochemically normal human muscles and seven muscles from boys with Duchenne muscular dystrophy (DMD) and 11 disease control muscles, (ii) the ultrastructural localization of aciculin in normal skeletal myofibers, (iii) aciculin's spacial relationship with dystrophin and beta-spectrin, and (iv) if the aciculin is ultrastructurally colocalized with dystrophin, the distance from the aciculin epitope to the epitope of the dystrophin N- or C-terminal domain. For this, rabbit anti-aciculin antibody was generated against the synthetic peptide of aciculin fragment D [4]. Immunohistochemical staining showed that the immunostainability of DMD muscles for anti-aciculin antibody was markedly decreased as compared with normal and disease control muscles. Single and double immunogold labeling electron microscopy of 6 histochemically normal human quadriceps femoris muscles revealed that aciculin was present along the inner surface of muscle plasma membrane and that aciculin formed doublets more frequently with dystrophin (23.5 +/- 1.8%; group mean +/- SE) than with beta-spectrin (12.8 +/- 1.1%; P < 0.01 two tailed t test). Rabbit anti-aciculin antibody frequently formed doublets with monoclonal antibodies against the N- or C-terminal domain of dystrophin at the muscle cell surface. These results suggest that aciculin is associated with dystrophin and may interact with both the N- and C-terminal domains of dystrophin.
Child↗
Unusual core histones specifically expressed in male gametic cells of Lilium longiflorum.
We have cloned three novel histone genes using antibodies that recognize only nuclei of the male gametic (generative and sperm) cells of Lilium longiflorum. The deduced amino acid sequence of each clone shows only between 40% and 50% identity with the H2A, H2B and H3 somatic core histones of other plant species. Transcripts of these genes were first detected in bicellular pollen soon after microspore mitosis, and their mRNAs, as revealed by in situ hybridization, were observed only in the cytoplasm of the generative cells. As expression of these three genes was specific to generative cells within the bicellular pollen, we designated the clones gH2A, gH2B and gH3. Immunocytochemistry further revealed that the proteins encoded by these genes accumulated in the elongating and condensing generative nucleus during development of bicellular pollen, and were most abundant in the two sperm nuclei within an elongated pollen tube. We therefore propose that these male gamete-specific core histones contribute to chromatin condensation of male gametes or to chromatin remodeling, and result in the repression of gene expression in male gametes.
Amino Acid Sequence↗
Post-ischemic intraportal adenosine administration protects against reperfusion injury of canine liver.
Although adenosine has been postulated to inhibit ischemia-reperfusion injury in various tissues, its in vivo cytoprotective mechanism is not fully known. The aim of this study was to determine the effect of intraportally infused adenosine on reperfusion injury in the canine liver. Two h ischemia and reperfusion of the liver were induced in beagle dogs by clamping the portal triad. Either adenosine or saline was infused in the portal vein after reperfusion for 60 min. Levels of serum aspartate aminotransferase and alanine aminotransferase and the survival of animals were examined. Hepatic levels of protein carbonyls and glutathione were also measured, as markers of oxidative stress. One h after reperfusion, the liver was perfused with nitroblue tetrazolium and the formation of formazan was observed to evaluate superoxide formation. Twenty-four h after reperfusion, 100% of animals in the adenosine group and 33% of animals in the control group survived. Adenosine significantly decreased the reperfusion-induced increase in serum levels of aspartate aminotransferase and alanine aminotransferase. Adenosine also suppressed the formation of protein carbonyls and the decrease in glutathione levels. Histologically, neutrophil infiltration, superoxide formation, and apoptosis were decreased by adenosine. These results suggest that intraportally infused adenosine attenuates reperfusion injury of the liver, presumably by suppressing the activation of neutrophils and oxidative stress.
Adenosine↗
Cox-2 expression in retinoblastoma.
PURPOSE: Cox-2, a prostaglandin synthase, is overexpressed in colorectal cancers and is involved in angiogenesis as well as in tumorigenesis. In this study, we investigate the expression of Cox-2 in retinoblastoma. METHODS: Twenty-nine formalin-fixed retinoblastoma specimens were examined by the labeled-streptavidin-biotin method using anti-Cox-2 antibody. RESULTS: Cox-2 positive immunoreactions were observed in 28 (96%) of 29 retinoblastomas specimens. CONCLUSION: This preliminary study suggests the overexpression of Cox-2 in both differentiated and undifferentiated retinoblastoma and its possible role in tumorigenesis.
Child, Preschool↗
Surgical results for small cell lung cancer based on the new TNM staging system. Thoracic Surgery Study Group of Osaka University, Osaka, Japan.
BACKGROUND: Operation with combined chemotherapy has been recently recommended for very early stage of small cell lung cancer without lymph node metastasis. METHODS: A retrospective study was undertaken in 91 patients who had undergone pulmonary resection for small cell lung cancer according to the new international staging system. RESULTS: The 5-year overall probability of survival was 37.1%. The 5-year survival rate was 100% for p-stage 0, 56.1% for p-stage IA, 30.0% for p-stage IB, 57.1% for p-stage IIA, and 42.9% for p-stage IIB. In the p-stage IA-IIB patients who underwent a complete resection, the 5-year survival rate of the patients treated by operation with chemotherapy was better than that of patients treated by operation alone. In addition, the 5-year survival rate of the patients who had four or more courses of chemotherapy was 80.0%. CONCLUSIONS: These results suggest that operation should be considered for p-stage IA-IIB patients and more than four courses of combined chemotherapy might be desirable in these resectable cases.
Adult↗