PubMed Health⌕ Search

Biomedical subjects

T Ueda

Publications and source records attributed to T Ueda.

At least 397 records · Page 22Linked to original sources
PubMed1998

Response-oriented individualized induction therapy with six drugs followed by four courses of intensive consolidation, 1 year maintenance and intensification therapy: the ALL90 study of the Japan Adult Leukemia Study Group.

Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.

Adult↗
PubMed1998

Response-oriented individualized induction therapy followed by intensive consolidation and maintenance for adult patients with acute lymphoblastic leukemia: the ALL-87 study of the Japan Adult Leukemia Study Group (JALSG).

The Japan Adult Leukemia Study Group conducted the ALL-87 study to determine whether response-oriented induction therapy and intensive consolidation and maintenance/intensification therapies could increase complete remission (CR) rate and survival in adult acute lymphoblastic leukemia (ALL). Of 121 patients registered, 116 were evaluated. Patients' ages ranged from 15 to 72 years (median, 38 years). Induction therapy, which consisted of doxorubicin, vincristine, cyclophosphamide, L-asparaginase and prednisolone, was given in a response-oriented individualized fashion. Patients were randomly allocated either to receive or not, intrathecal chemotherapy on day 8 of the induction therapy. Complete remission (CR) was obtained in 97 (83.6%) patients (90.2%) in patients of less than 50 years of age and 67.6% in patients 50 years of age or older). At a median follow-up period of 65 months, the predicted 6-year overall survival and event free survival (EFS) rates of 116 patients were 23.4 and 20.0%, respectively. Predicted 6-year survival and disease-free survival (DFS) rates of 97 CR patients were 28.2 and 24.5%, respectively. By multivariate analysis, patients under 40 years of age (P = 0.002) or those with a platelet count of more than 100,000/microliters (P = 0.004) were significant favorable prognostic factors for obtaining CR, and days to CR less than 50 (P = 0.003), patients under 50 years of age (P = 0.005) were significant favorable factors for longer DFS. There was no significant difference in CR rates and DFS between the two randomized groups according to the intrathecal chemotherapy on day 8. Response-oriented induction therapy produced a high CR rate, but fairly intensive consolidation and maintenance/intensification chemotherapies resulted in only a marginal effect on DFS in adult ALL. Although age is one of the most important prognostic factors in ALL, the outcome was unsatisfactory even in younger adult patients using chemotherapeutic regimen employed in this study.

Adolescent↗
PubMed1998

Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2.

Bone morphogenetic protein (BMP) is a potent inducer of ectopic bone formation, and TNP-470, a synthetic analog of fumagillin, is an antiangiogenic agent that strongly inhibits neovascular formation in vivo. We investigated the effects of TNP-470 on BMP-induced ectopic bone formation to clarify the role of angiogenesis in bone formation. Collagen pellets containing recombinant human BMP-2 (rhBMP-2) were implanted beneath the fasciae of dorsal muscles in mice. By daily subcutaneous administration of TNP-470, ectopic new bone formation was inhibited in a dose-dependent manner. Histological examination revealed that TNP-470 prevented proliferation of mesenchymal cells and chondrogenesis at the initial step of endochondral bone formation. Immunohistochemical staining with a specific antibody against bone morphogenetic protein type IA receptor showed that TNP-470 reduced the number of receptor-positive cells surrounding the BMP pellets. The inhibitory effect of TNP-470 on bone formation continued during the period of its administration, and discontinuation of treatment was followed by the resumption of the whole process of endochondral bone formation. This study showed that TNP-470 reversibly inhibits the biological activity of rhBMP-2 in the early stage of bone induction, suggesting that angiogenesis may play an essential role in the recruitment of BMP-receptor-positive cells that can respond to rhBMP-2 and differentiate into chondrocytes and/or osteoblasts.

Animals↗
PubMed1998

Histochemical studies on sialic acids in the epididymis during post-natal development of the rat.

A variety of sialic acids contained in the rat epididymis during post-natal development were examined by means of lectin and carbohydrate histochemistry. Epididymides from male Sprague-Dawley rats on post-natal days 14, 21, 30, 39, 49, 56 and 70 were fixed in Bouin's fluid and embedded routinely in paraffin wax. Hydrated sections were subjected either to the lectin methods using biotinylated Sambucus sieboldiana lectin or Maackia amurensis lectin or to the selective periodate oxidation-phenylhydrazine-thiocarbohydrazide-silver protein-physical development technique with or without saponification. The results revealed that sialic acids appeared in the epididymal epithelium at day 14, followed by particular distribution patterns corresponding to cell differentiation during days 21-39. High-level O-acetylation of sialic acids was observed in the principal cells of the initial segment and proximal caput after day 39. These results suggest that sialic acids with different linkages and O-acetylation become adult in distribution at the 'differentiation' period under the influence of androgen, before spermatozoa reach the epididymal lumen. Such carbohydrates may be correlated, at least in part, with sperm-binding sialoproteins, which increase dramatically during the window between days 21 and 39.

Animals↗
PubMed1998

Biochemical and immunological characterization of rice homologues of the human immunodeficiency virus-1 Tat binding protein and subunit 4 of human 26S proteasome subunits.

Previously, we isolated two cDNA clones, TBPOs-1 and TBPOs-2, encoding putative ATPases that are the rice homologues of human immunodeficiency virus-1 (HIV-1) Tat binding protein-1 and subunit 4 of human 26S proteasome. In order to determine the RNA-dependent ATPase activity of these putative proteins, the subclones from these cDNA clones were expressed in Escherichia coli as fusion proteins with maltose-binding protein. The recombinant proteins stimulated ATP hydrolysis in the presence of poly(U) and rice total RNA. In contrast, single- and double-stranded forms of HindIII-digested lambda phage DNA are less effective at stimulating ATP hydrolysis. Western blot analysis using antisera against the TBPOs proteins showed a widespread appearance of these proteins in rice tissues and cultured cells. The TBPOs proteins were also found around the region where rice proteasomes would sediment. In addition, the TBPOs-1 protein bound to tobacco TATA-binding protein in vitro. Thus, we suggest that the TBPOs proteins are novel RNA-dependent ATPases characteristic of DEAD-box proteins and propose that the TPBOs proteins can exist in rice proteasomes. Further, the TBPOs-1 protein is thought to play a role in transcriptional events.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1998

Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-alpha, vascular endothelial growth factor and platelet-derived growth factor.

To test the hypothesis that oxidative damage associated with tissue hypoxia plays a role in neovascularization, a lipid hydroperoxide (LHP) was injected into the vitreous of rabbits. Single injections of LHP (50-600 microg) caused a sustained retinal neovascularization visualized clinically by ophthalmoscopy and confirmed by microscopy. Vasodilators, i.e. histamine and nitric oxide, peaked at 6h and 7 days, respectively. The levels of both tumor necrosis factor-alpha and interleukin-1alpha peaked at 12h and dropped to basal levels by 24h. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta peaked at 24h and were sustained throughout the following 3 weeks, and platelet-derived growth factor was also elevated throughout the same period. Upregulation of these five angiogenic cytokines, but not basic fibroblast growth factor, occurred prior to the appearance of neovascularization. Leakage of fluorescein at the tips of new vessels was demonstrated by fluorescein angiography. Linoleic hydroperoxide induced neovascularization, but saturated or unsaturated native C-18 fatty acids had no effect. The cascade of multiple, angiogenic cytokines induced by LHP may interact to promote sustained neovascularization.

Journal Article↗
PubMed1998

Biphasic expression of CD4 in acute myelocytic leukemia (AML) cells: AML of monocyte origin and hematopoietic precursor cell origin.

In 227 of 495 (45.9%) Japanese adult patients with acute myelocytic leukemia (AML), leukemic cells expressed CD4. Incidence of CD4 expression in each FAB subtype was as follows: M1 37.4%, M2 33.7%, M3 35.4%, M4 65.0%, and M5 78.3%. The typical expression pattern of myelomonocytic differentiation antigens and cytokine receptors in CD4+ AML was CD34lowCD33high CD11bhighGM-CSFRhigh. AML cases with 11q23 abnormalities and with inv(16) were frequently CD4-positive. These data collectively indicate that CD4 expression in AML cells is associated with monocytic characteristics. However, CD4+CD34high AML cases appear to have unique immature characteristics including low expression of myelomonocytic differentiation antigens (ie CD33 and CD11b), and accumulation of chromosome abnormalities (ie t(8;21) in CD4lowCD34high AML and chromosome 7 abnormalities in CD4highCD34high AML). We speculate that these leukemia subsets originate from CD4+ hematopoietic precursor cells, therefore then should be considered separately from most of the CD4+ AML as represented by CD34lowCD33high CD11bhighGM-CSFRhigh. Overall survival of patients with CD4+ AML in our series was worse than that of those with CD4 AML (P = 0.0202).

Adult↗
PubMed1998

The expression of co-stimulatory molecules and their relationship to the prognosis of human acute myeloid leukaemia: poor prognosis of B7-2-positive leukaemia.

We examined the expression of co-stimulatory molecules on leukaemic cells of 52 adult patients with acute myeloid leukaemia (AML) (34 men and 18 women) and analysed the relationship between these expressions and the patient's prognosis. B7-1 was not expressed in any of the 23 patients investigated, whereas B7-2 was expressed in 26/52 patients (50.0%). B7-2 was expressed in all AML patients with monocytic morphology (M4 or M5) and in 16/42 cases without monocytic morphology. CD54 was expressed in 28/ 37 patients examined (75.7%), and CD58 was expressed in all of the AML patients except one (M 7). The overall survival of the 26 B7-2-positive leukaemia patients (1-24 months, median survival 11.5 months) was significantly shorter than that of the 26 B7-2-negative leukaemia patients (1-71+ months, median 35.1 months) (P=0.0080). In addition, the B7-2-positive patients exhibited significantly shorter disease-free survival periods compared to the B7-2-negative patients (P=0.021). There was no significant difference in age, sex, haematological data and complete remission rate between the B7-2-positive and B7-2-negative patients. Our results indicated that B7-2 is one of the most crucial factors in the prognosis of adult acute leukaemia and can be expected to have an important role in tumour immunity.

Acute Disease↗
PubMed1998

Reconstruction after total gastrectomy by the interposition of a double jejunal pouch using a double stapling technique.

BACKGROUND: After total gastrectomy, sustaining good nutrition is extremely important for maintaining quality of life. A technique of neogastric pouch formation based on current physiological reconstructive principles is presented. METHODS: The use of a modified interpositioned double jejunal pouch following total gastrectomy in 18 patients with cancer was reviewed. This technique results in a complete pouch and uses a double stapling technique with site-specific anastomosis between the oesophagus and pouch, in which a Hisoid angle is created. RESULTS: There were no anastomotic leaks and pouch blood flow was within normal expected limits. Mean oesophageal pH above 7.0 for one 24-h period was 7.7 per cent. Emptying half-time was 67.8 min. After 2 years mean body-weight was 98.3 per cent of expected, mean food volume was 94.0 per cent of expected and mean meal frequency was 3.0 per day. CONCLUSION: This form of gastric reconstruction is an acceptable procedure which improves the quality of life in patients undergoing total gastrectomy.

Adult↗
PubMed1998

Tolerogenic activity of polyethylene glycol-conjugated lysozyme distinct from that of the native counterpart.

Conjugation of proteins with polyethylene glycol (PEG) has been reported to make the proteins tolerogenic. Native proteins are also potentially tolerogenic when given without adjuvants. We compared immunotolerogenic activities between PEG-conjugated and native hen egg-white lysozyme (HEL). BALB/c mice were given consecutive weekly intraperitoneal administrations of PEG-conjugated HEL, unmodified HEL or phosphate-buffered saline (PBS), for 3 weeks, then challenged with HEL in Freund's complete adjuvant. The pretreatment with PEG-HEL tolerized both T-cell and humoral responses, while native HEL tolerized only the T-cell response. Immunoglobulin G1 (IgG1) antibody was already elevated in HEL-pretreated mice prior to challenge immunization, followed by suppressed IgG2a and IgG2b, but spared IgG1 production after the antigen challenge, whereas PEG-HEL-pretreated mice produced no antibody in all IgG subclasses prior and subsequent to the antigen-challenge. Production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by lymphoid cells in response to HEL in vitro was markedly suppressed in both the antigen-pretreated groups, while suppression of IL-4 production was evident only in PEG-HEL-, not in HEL-pretreated animals. Involvement of suppressor cells in these tolerance states was found to be unlikely, and the immunological property of PEG-HEL differed from deaggregated HEL that was similar to the original HEL. These results suggest a unique immunotolerogenic activity of PEG-conjugated proteins to suppress both T-helper type-1 (Th1)- and Th2-type responses, the result being extensive inhibition of all IgG subclass responses, while tolerance induction by unconjugated soluble proteins tends to be targeted on Th1-, but spares Th2-type responses.

Adjuvants, Immunologic↗
PubMed1998

Influence of hyperlipidemia and smoking on age-related changes in caloric response and pure-tone hearing.

To examine the influence of hyperlipidemia and smoking on age-related changes in caloric response and pure-tone hearing, a caloric test and pure-tone audiometry were performed in 14 healthy volunteers and in 78 tinnitus patients without subjective hearing loss. The patients were from 24 to 84 years of age, and were divided into 4 groups: the no-risk group (N group), the smoking alone group (S group), the hyperlipidemia alone group (L group), and the smoking plus hyperlipidemia group (S-L group). Slow phase eye velocity of the caloric nystagmus (SPEV) and average hearing level at high frequencies were compared between the N groups and the other groups. There was a significant difference in SPEV only between the N and S-L groups, but not in the hearing level. This suggests that age-related changes in the caloric response be promoted by atherosclerosis, unlike presbycusis.

Adult↗
PubMed1998

Production of immunoreactive 2',5'-oligoadenylate synthetase in p48-deficient mice.

2',5'-Oligoadenylate synthetase (2'5'OAS), an enzyme induced by interferon (IFN), is physiologically produced in IFN-untreated normal healthy mice. The enzyme is localized mainly in the epithelium of the digestive tract, reproductive organs, and the choroid plexus in the brain. 2'5'OAS is also detected in oocytes in the ovary and in neurons and glial cells of both the telencephalon and cerebellum. Here, we examined the role of p48 (ISGF3gamma), a component of IFN-stimulated gene factor 3 (ISGF3), in the physiologic production of 2'5'OAS using p48-deficient mice generated by gene targeting. In the p48-deficient mice, the physiologic production of 2'5'OAS localized in the following cells was severely impaired: hepatocytes, Kupffer cells, splenocytes, epithelium of the large intestine, oviduct, and uterus, and neurons and glial cells in both the telencephalon and cerebellum. The results show that 2'5'OAS in these cells is induced physiologically through a pathway including p48. However, the production of 2'5'OAS in oocytes was not affected in the p48-deficient mice, indicating that oocyte 2'5'OAS is produced through a p48-independent pathway. A possible function of the GAS sequence found in the promoter region of the 2'5'OAS gene to which Stat6 may bind also is discussed.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

The target cells of injected type I interferons in mouse liver.

Type I interferons (IFNs) have been used for the treatment of viral hepatitis, but it is unclear which cells in the liver are affected by injected IFN. The effects of IFN have been studied by the production of 2',5'-oligoadenylate synthetase (2'5'OAS), an IFN-inducible enzyme. Here, we studied the distribution of 2'5'OAS in mouse liver after injection of natural mouse IFN-alpha/beta by Western blotting and immunohistochemistry using a monoclonal antibody specific to mouse 42-kDa 2'5'OAS. Injection of IFN-alpha/beta increased the levels of liver 2'5'OAS and enhanced the intensities of immunohistochemical staining for this enzyme in both hepatocytes and Kupffer cells. In IFN-untreated normal mice, hepatocytes were lightly stained, but some of the Kupffer cells showed rather strong staining. The 2'5'OAS-positive Kupffer cells comprised approximately 60% of those in normal liver, whereas this increased to approximately 90% following IFN-alpha/beta injection. Thus, hepatocytes and Kupffer cells were the targets of injected IFN.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

Endometriosis and uterine leiomyomata with ovarian granulosa cell tumour.

We report the first known case of right endometrial cyst and multiple uterine leiomyomata complicated by an ovarian granulosa cell tumour of adult type. A 42 year old woman had an adult type left granulosa cell tumour. Laparoscopy 13 years earlier had revealed a small endometrial implant on the peritoneum, without uterine leiomyomata or bilateral ovarian tumours. Findings in this case suggest that the aetiology of endometriosis and uterine leiomyomata are related to the presence of an oestrogen-secreting neoplasm and that the presence of a state of hyperoestrogenaemia due to granulosa cell tumour over several years might have stimulated the development of endometriosis and leiomyomata.

Adult↗
PubMed1998

Detection of a local interaction of hen lysozyme under highly denaturing conditions using chemically 13C-enriched methionine resonance.

Using hen lysozyme in which the epsilon-carbons of two methionine residues are enriched with 13C nuclei, we found that there is a subtle difference in the chemical shift of the epsilon-carbon resonances between Met 12 and Met 105 in thermally denatured lysozyme without any reduction of disulfide bonds at pD 3.8, and also in reduced S-alkylated lysozyme at pD 3.8 and 35 degrees C. The difference in the chemical shift was abolished on digestion with TPCK-trypsin and the chemical shifts of both resonances converged to that of Met 12, whose chemical shift is identical to that in the randomly coiled state. Therefore, it is suggested that the chemical shift in the epsilon-carbon resonance of Met 105 is different from that in the randomly coiled state due to an interaction involving Met 105. In order to locate the interaction involving Met 105, fragmentation of the reduced S-alkylated lysozyme into the peptides was carried out by means of chemical cleavage or specific endoprotease digestion. As a result, the local interaction of Met 105 or the residues around Met 105 with eleven residues at the C-terminus of lysozyme is suggested to occur.

Alkylation↗
PubMed1998

Kinetic measurement of the interaction between a lysozyme and its immobilized substrate analogue by means of surface plasmon resonance.

A method for evaluating the association and dissociation rate constants of interaction between a lysozyme and its substrate analogue, an immobilized p-aminophenyl-tri-N-acetyl-beta-chitotrioside, by means of surface plasmon resonance has been developed. Site-specific immobilization of p-aminophenyl-tri-N-acetyl-beta-chitotrioside, which is a product of p-nitrophenyl-tri-N-acetyl-beta-chitotrioside, on carboxymethyldextran linked to the surface of the cuvette of the instrument, IAsys, was carried out by catalysis with EDC/NHS. The kinetic parameters of the interaction between hen or human lysozyme and the immobilized substrate analogue indicated that a larger dissociation constant of the human lysozyme-immobilized substrate analogue complex depended on a smaller association rate constant. The kinetic parameters of the interaction between the immobilized substrate analogue and a mutant hen lysozyme, in which Arg14 and His15 are deleted, with higher activity than the wild type hen lysozyme were measured. It was suggested that the higher activity of the mutant lysozyme was due to faster removal of the substrate from the active site cleft and/or the formation of a stabler and better complex as to hydrolysis.

Animals↗