Search PubMed⌕ Search

Biomedical subjects

T Okamoto

Publications and source records attributed to T Okamoto.

At least 199 records · Page 11Linked to original sources
PubMed2000

Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome.

Bone marrow transplantation has been established as a useful treatment for various hematological disorders and is now performed widely, but the mortality rate is still high due to various complications. A clear therapeutic policy for such complications has not yet been established because of their complex nature. We investigated whether the major complications occurring after bone marrow transplantation could be classified as aspects of the systemic inflammatory response syndrome. Subjects were 10 patients who developed severe complications after bone marrow transplantation (graft-versus-host disease, thrombotic microangiopathy, respiratory disorders, and cytomegalovirus interstitial pneumonitis) and 16 patients without complications. Their symptoms, serum cytokines, and factors related to vascular endothelial damage were compared before and after transplantation. Whereas all 10 patients who developed complications had fever in the aplastic phase after transplantation, 15 of the 16 patients without complications remained afebrile (P < 0.001, t-test). When compared with the patients who did not develop complications, the patients with complications also showed significantly higher cytokine levels during the recovery phase after transplantation (P < 0.0001, t-test). Thus, the patients with complications developed fever in the aplastic phase and showed an increase of cytokines during the recovery phase, which triggered the occurrence of vascular endothelial damage shown by factors such as the thrombomodulin and plasminogen activator inhibitor type 1. This sequence of events corresponds with that occurring during systemic inflammatory response syndrome, so many of the complications of bone marrow transplantation can be considered as manifestations of this syndrome.

Adult↗
PubMed2000

Predicting the severity of intestinal graft-versus-host disease from leukotriene B4 levels after bone marrow transplantation.

Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and histological changes resembling those of ulcerative colitis and has been treated with drugs which are used for ulcerative colitis. These two conditions also resemble each other with respect to changes of cytokines. Accordingly, we investigated whether the level of leukotriene B4, a risk factor for ulcerative colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The pre-conditioning leukotriene B4 level was significantly related to the grade of intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not develop severe intestinal GVHD after bone marrow transplantation, those who did had significantly higher interleukin-2 and interferon-gamma levels during the aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels during the recovery phase (P < 0.0001), with significant elevation of tumor necrosis factor-alpha and interferon-gamma occurring in association with exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the possibility that leukotriene B4 may be a useful prognostic indicator for intestinal GVHD.

Adolescent↗
PubMed2000

A novel in vitro effect of the mucosal protective agent sofalcone--inhibition of chemotactic motility in Helicobacter pylori.

BACKGROUND: Motility of Helicobacter pylori is essential for colonization. H. pylori has been shown to exhibit chemotactic activity toward urea and sodium and bicarbonate ions, which are secreted from the gastric epithelia. The importance of urease activity for chemotactic motility of H. pylori in a viscous environment has also been shown. Consequently, application of drugs inhibiting chemotactic motility has been proposed as a strategy for H. pylori eradication. This inhibitory effect can be evaluated through assay of chemotaxis and swarming. MATERIALS AND METHODS: H. pylori CPY3401 and ATCC43504 were grown on brucella agar plates/broth supplemented with 3% horse serum under microaerobic conditions (N2, 85%; O2, 5%; CO2, 10%). For motility assay, H. pylori cells grown on brucella-serum agar were stabbed into motility agar containing 0.35% refined agar in brucella-serum broth and the swarming zone was measured. For the chemotaxis assay, cells were suspended in 10 mM potassium phosphate buffer, pH 7.0, with 3% polyvinyl-pyrrolidone and assayed as described previously. Bacterial swimming in the fluid environment was observed under dark-field microscopy. RESULTS: Numbers of bacteria attracted toward 1 microM flurofamide were reduced with increasing concentrations of sofalcone (0.2-222 microM). In addition, the size of the swarming zone was reduced in motility agar containing 22 and 222 microM sofalcone. On the other hand, 22 microM sofalcone did not inhibit bacterial growth on day 3. Bacterial swimming speed in brucella broth was slower in the presence of 22 and 222 microM sofalcone than in its absence. CONCLUSION: Sofalcone was found to inhibit chemotactic motility of H. pylori. This drug may be useful for inhibiting the bacterium's ability to colonize the human stomach.

Anti-Ulcer Agents↗
PubMed2000

Biodegradation of didecyldimethylammonium chloride by Pseudomonas fluorescens TN4 isolated from activated sludge.

Bacteria that degrade didecyldimethylammonium chloride (DDAC) were isolated from activated sludge from a municipal sewage treatment plant by enrichment culture with DDAC as a sole carbon source. One of the isolates, Pseudomonas fluorescens TN4, degraded DDAC to produce decyldimethylamine and subsequently, dimethylamine, as the intermediates. The TN4 strain also assimilated the other quaternary ammonium compounds (QACs), alkyltrimethyl- and alkylbenzyldimethyl-ammonium salts, but not alkylpyridinium salts. TN4 was highly resistant to these QACs and degraded them by an N-dealkylation process. These data mean that there are some QAC-resistant and QAC-degrading bacteria such as TN4 in the environment.

Biodegradation, Environmental↗
PubMed2000

Mutational analysis of the functional motifs of RuvB, an AAA+ class helicase and motor protein for holliday junction branch migration.

Escherichia coli RuvB protein, together with RuvA, promotes branch migration of Holliday junctions during homologous recombination and recombination repair. The RuvB molecular motor is an intrinsic ATP-dependent DNA helicase with a hexameric ring structure and its architecture has been suggested to be related to those of the members of the AAA+ protein class. In this study, we isolated a large number of plasmids carrying ruvB mutant genes and identified amino acid residues important for the RuvB functions by examining the in vivo DNA repair activities of the mutant proteins. Based on these mutational studies and amino acid conservation among various RuvBs, we identified 10 RuvB motifs that agreed well with the features of the AAA+ protein class and that distinguished the primary structure of RuvB from that of typical DNA/RNA helicases with seven conserved helicase motifs.

Amino Acid Sequence↗
PubMed2000

Expression of aminopeptidase A in human gestational choriocarcinoma cell lines and tissues.

Aminopeptidase A (AP-A), a cell-surface metallopeptidase hydrolyzing peptide with N-terminal acidic residues, has been proved to be identical to the B cell differentiation antigen BP-1 and to the kidney differentiation antigen gp160, suggesting recognition of AP-A as a differentiation-related marker on certain normal and transformed cells. AP-A has also been purified from human placenta and been shown to be localized in the trophoblasts. In the present study, we examined the expression and enzymatic activity of AP-A in human gestational choriocarcinoma, a neoplastic transformant from trophoblasts which comprises a heterogenous population of trophoblastic cells in different stages of differentiation. Flow cytometry and immunoblot analysis demonstrated that AP-A was expressed in five choriocarcinoma cell lines which were secreting low or moderate levels of human chorionic gonadotropin (hCG), while two high hCG-secreting cell lines lacked AP-A expression. The AP-A enzymatic activity correlated with cell-surface levels of AP-A and was abrogated by amastatin, an inhibitor of AP-A. Immunohistochemical analysis revealed that AP-A was present in seven of eight choriocarcinoma tissues and was localized on the cell membrane of cytotrophoblastic choriocarcinoma cells, but not on cells with syncytiotrophoblast-like features. These results demonstrate that AP-A is expressed on most choriocarcinomas and its expression is restricted to low hCG-secreting, cytotrophoblastic cells and down-regulated as a function of cell differentiation, suggesting an involvement of AP-A in the differentiation/maturation process of neoplastic trophoblasts.

Amino Acid Sequence↗
PubMed2000

Embolisation of cerebral arteriovenous malformations to assure successful subsequent radiosurgery.

This study investigated the angiographic changes in embolised arteriovenous malformations (AVMs) pre- and post-embolisation and preradiosurgery to clarify the usefulness of embolisation as a pretreatment for radiosurgery and the strategy of embolisation for the radiosurgical success. A total of 37 patients with cerebral AVMs treated over a period of 4 years was investigated. All the AVMs were embolised with N-butyl cyanoacrylate and 2 months later they were treated by radiosurgery. The size of AVM nidus reduced just following the embolisation (mean 21.9 ml to 3.9 ml). The angiogram taken in preparation for radiosurgery showed a further size reduction in the nidus of 16 AVMs, no change in 10 and regrowth in 11. In all the cases where size was reduced, the nidus was densely packed, while all the regrown AVMs were of the diffuse type. Five AVMs disappeared following radiosurgery, all of which were size-reduction or no-change cases. In conclusion, to achieve success in subsequent radiosurgery, nidus embolisation and the occlusion of fistulous and meningeal feeders are mandatory. Imprudent proximal feeder occlusion and the use of embolic materials with a risk of recanalisation should be avoided to prevent regrowth of the nidus, which may lead to errors in planning the radiosurgery to follow.

Adolescent↗
PubMed2000

Somatic mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in patients with sporadic, nonfamilial primary hyperparathyroidism.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome with tumors of many endocrine tissues. Germline MEN1 gene mutations were found in most patients with familial or sporadic MEN 1. Recently, somatic MEN1 gene mutations were also detected in sporadic non-MEN 1 endocrine tumors. METHODS: We used direct sequence analysis to investigate MEN1 gene mutations in 30 parathyroid tumors obtained from 30 patients with sporadic, nonfamilial primary hyperparathyroidism. RESULTS: Four patients had somatic mutations of the MEN1 gene, comprising 1 small insertion (1091insAGC), one missense mutation (G42S), and 2 non-sense mutations (E388X, R460X). Identical missense and non-sense mutations were found in patients with familial and non-familial MEN 1. There were no differences between clinical features of patients with and without MEN1 gene mutations. CONCLUSIONS: The incidence of somatic MEN1 gene mutations (13.3%) in Japanese patients with sporadic, nonfamilial primary hyperparathyroidism is almost equal to those of such patients in the United States and Sweden. Occasionally, the MEN1 gene mutation sites in sporadic parathyroid tumors are identical to those reported in tumors from patients with familial or sporadic MEN 1.

DNA↗
PubMed2000

Enhanced invasion of Tax-expressing fibroblasts into the basement membrane is repressed by phosphorylated ascorbate with simultaneous decreases in intracellular oxidative stress and NF-kappa B activation.

Invasion of rat fibroblastic cells Rat-1 through Matrigel was shown to be promoted by transfection with tax gene of human T-cell leukemia virus type 1. We found that an oxidation-resistant type of vitamin C (Asc), Asc-2-O-phosphate (Asc2P), inhibited the invasion of the tax-transfected Rat-1 cells (W4 cells). Intracellular Asc (Ascin), after enzymatic dephosphorylation of administered Asc2P, was more abundant in W4 cells than in Rat-1 cells, and the ratio of dehydroascorbic acid versus Asc was increased in W4 cells but scarcely in Rat-1 cells, according to the enhanced level of intracellular reactive oxygen species (ROSin) in W4 cells. Asc2P notably repressed the increases in both ROSin and secretion of matrix metalloproteases (MMPs), but did not affect Tax protein expression in tax-transfectants. NF-kappa B activation, as evidenced by its translocation to the nucleus in W4 cells, was also repressed by Asc2P. Thus, the tax-promoted invasion together with the enhanced production of MMPs occurred with NF-kappa B activation and the increase in ROSin, both of which were effectively reduced by Asc2P. These findings indicate the therapeutic efficacy of Ascin-enriching agents for the prevention against tumor invasion in which ROSin plays a major role.

Animals↗
PubMed2000

Long-term follow-up of clinical symptoms in TMD patients who underwent occlusal reconstruction by orthodontic treatment.

Fifty-eight patients (mean age 18.4 years) who had received splint therapy for internal derangement of the temporomandibular joint (TMJ) were examined retrospectively to investigate the efficacy of occlusal reconstruction by orthodontic treatment. The subjects were divided into three groups: 18 patients (mean age 18.6 years) who underwent orthodontic treatment combined with the use of splints (ST group); 27 patients (mean age 18.2 years) who underwent orthodontic treatment without the use of splints (NST group); and 13 patients (mean age 17.9 years) who received only splint therapy for temporomandibular joint disorders (TMD; control group). TMJ sound, pain on movement and restriction of mandibular movement were examined at the initial examination (T1), at the end of the splint therapy for TMD or beginning of orthodontic treatment (T2), at the end of orthodontic treatment (T3), and at recall or 1 year after orthodontic treatment (T4). The following results were found. (1) The percentage of patients with no joint sound at T2 was 20-30 per cent. The percentage of such patients in both the ST and NST groups increased to over 50 per cent at T3, but slightly decreased to 39-50 per cent at T4. There were no significant inter-group differences at any time point. (2) The number of patients who had no pain on movement at T2 was 60-80 per cent. The percentage of such patients in both the ST and NST groups increased to over 90 per cent at T3, but then slightly decreased to 80 per cent at T4. There were no significant inter-group differences at any time point. (3) None of the patients showed restriction of movement of the TMJ at T2 or T4. One patient in the ST group was found to have restriction at T3. There were no significant inter-group differences at any time point. (4) The most frequent type of malocclusion in both ST and NST groups was anterior open bite. These results suggest that TMD symptoms that have been eliminated by splint therapy are not likely to recur due to subsequent orthodontic treatment, but it cannot be concluded that orthodontic treatment itself had a positive effect on TMD symptoms. The results also indicate that there is a relationship between anterior open bite and TMD.

Adolescent↗
PubMed2000

Immunolocalization of progesterone and estrogen receptors in the sperm storage tubules of laying and diethylstilbestrol-injected immature hens.

The goal of this study was to determine whether sperm storage tubules (SST) in the uterovaginal junction (UVJ) contain receptors for progesterone and estrogen (PR and ER) and whether estrogenic stimulation induces activation of these receptors in the SST. Frozen sections of UVJ obtained from immature chicks treated with or without diethylstilbestrol (DES), which is an estrogenic substance, and those from laying hens were immunostained for PR and ER. In laying hens, immunoreactions for PR were observed in the SST cells and on the surface epithelium of UVJ; the strongest reactions appeared in the SST cells. In contrast, ER immunoreactions were localized in the SST cells but not in the other cells. Immunoreactions for PR and ER were negligible in the UVJ of control immature birds that received only the oil vehicle. However, in the DES-treated birds, PR immunoprecipitates were localized in the surface epithelium and SST cells, and there were ER in the SST cells. These results suggest that the SST cells in the UVJ contain PR and ER, and estrogenic stimulation may play a significant role in inducing activation of these receptors.

Animals↗
PubMed2000

Mutation in the threonine synthase gene results in an over-accumulation of soluble methionine in Arabidopsis.

In higher plants, O-phosphohomoserine (OPH) represents a branch point between the methionine (Met) and threonine (Thr) biosynthetic pathways. It is believed that the enzymes Thr synthase (TS) and cystathionine gamma-synthase (CGS) actively compete for the OPH substrate for Thr and Met biosynthesis, respectively. We have isolated a mutant of Arabidopsis, designated mto2-1, that over-accumulates soluble Met 22-fold and contains markedly reduced levels of soluble Thr in young rosettes. The mto2-1 mutant carries a single base pair mutation within the gene encoding TS, resulting in a leucine-204 to arginine change. Accumulation of TS mRNA and protein was normal in young rosettes of mto2-1, whereas functional complementation analysis of an Escherichia coli thrC mutation suggested that the ability of mto2-1 TS to synthesize Thr is impaired. We concluded that the mutation within the TS gene is responsible for the mto2-1 phenotype, resulting in decreased Thr biosynthesis and a channeling of OPH to Met biosynthesis in young rosettes. Analysis of the mto2-1 mutant suggested that, in vivo, the feedback regulation of CGS is not sufficient alone for the control of Met biosynthesis in young rosettes and is dependent on TS activity. In addition, developmental analysis of soluble Met and Thr concentrations indicated that the accumulation of these amino acids is regulated in a temporal and spatial manner.

Amino Acid Sequence↗
PubMed2000

Synergistic suppressive effect of double transfection of tumor necrosis factor-alpha and interleukin 12 genes on tumorigenicity of Meth-A cells.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin 12 (IL-12), both potent antitumor cytokines, are known to be involved in the host's antitumor immune surveillance in tumor bearers, via different mechanisms. The former enhances the activities of dendritic cells, natural killer / lymphocyte-activated killer (NK / LAK) and cytotoxic T lymphocyte (CTL), while the latter induces Th1-type cellular immunity and enhances the activities of natural killer T (NKT), NK / LAK and CTL. In the present study, in the expectation of synergistic actions of these cytokines in stimulating the host's immune responses, we investigated the feasibility of a cancer vaccine involving double transfection with both genes in a murine model. The expression of major histocompatibility complex (MHC) class I, class II and B7.1 on the surface of the double transfectants was enhanced as revealed by FACS analysis. A significant decrease in tumorigenicity was observed in mice inoculated with the double transfectants. Cytotoxicity assay revealed that the activities of NK / LAK and CTL from spleens of mice bearing the double transfectants were enhanced. The induction of tumor-specific immunity was confirmed by rechallenge with parental Meth-A cells in mice that had rejected the double transfectants. Thus, double transfection of TNF-alpha and IL-12 genes was considered to bring about synergistic suppressive effects on the tumorigenicity of transfectants through the activation of killer cells by produced cytokines and the enhancement of expression of MHC class I, II and B7.1 molecules.

Adenocarcinoma↗
PubMed2000

Inactivation of the glutamate decarboxylase gene in Lactococcus lactis subsp. cremoris.

Lactococcus lactis subsp. lactis strains show glutamate decarboxylase activity, whereas L. lactis subsp. cremoris strains do not. The gadB gene encoding glutamate decarboxylase was detected in the L. lactis subsp. cremoris genome but was poorly expressed. Sequence analysis showed that the gene is inactivated by the frameshift mutation and encoded in a nonfunctional protein.

Base Sequence↗
PubMed2000

A serine protease-encoding gene (aprII) of Alteromonas sp. Strain O-7 is regulated by the iron uptake regulator (Fur) protein.

The ferric uptake regulator (Fur) box-like sequence was located upstream of the serine protease-encoding gene (aprII) from a marine bacterium, Alteromonas sp. strain O-7. To clarify whether the production of AprII (the gene product of aprII) is regulated by the environmental iron concentrations, this strain was cultured under iron-depleted or iron-rich conditions and the level of AprII in the culture supernatant was analyzed by Western blotting. The production of AprII was significantly repressed under iron-rich conditions. Northern hybridization analysis demonstrated that AprII biosynthesis was regulated by iron through the control of transcription. These results indicate that aprII is a new member of the iron regulon and plays an important role in the iron acquisition system of the strain. Furthermore, the gene encoding Fur was cloned and sequenced. The deduced amino acid sequence of the cloned Fur showed high sequence similarity with that from gram-negative bacteria.

Alteromonas↗
PubMed2000

Loss of G(1)/S checkpoint in human immunodeficiency virus type 1-infected cells is associated with a lack of cyclin-dependent kinase inhibitor p21/Waf1.

Productive high-titer infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile reverse transcripts and lack of viral progeny formation. An interplay between Tat and p53 has previously been reported, where Tat inhibited the transcription of the p53 gene, which may aid in the development of AIDS-related malignancies, and p53 expression inhibited HIV-1 long terminal repeat transcription. Here, by using a well-defined and -characterized stress signal, gamma irradiation, we find that upon gamma irradiation, HIV-1-infected cells lose their G(1)/S checkpoints, enter the S phase inappropriately, and eventually apoptose. The loss of the G(1)/S checkpoint is associated with a loss of p21/Waf1 protein and increased activity of a major G(1)/S kinase, namely, cyclin E/cdk2. The p21/Waf1 protein, a known cyclin-dependent kinase inhibitor, interacts with the cdk2/cyclin E complex and inhibits progression of cells into S phase. We find that loss of the G(1)/S checkpoint in HIV-1-infected cells may in part be due to Tat's ability to bind p53 (a known activator of the p21/Waf1 promoter) and sequester its transactivation activity, as seen in both in vivo and in vitro transcription assays. The loss of p21/Waf1 in HIV-1-infected cells was specific to p21/Waf1 and did not occur with other KIP family members, such as p27 (KIP1) and p57 (KIP2). Finally, the advantage of a loss of the G(1)/S checkpoint for HIV-1 per se may be that it pushes the host cell into the S phase, which may then allow subsequent virus-associated processes, such as RNA splicing, transport, translation, and packaging of virion-specific genes, to occur.

CDC2-CDC28 Kinases↗
PubMed2000

Long-term administration of oral low-dose topoisomerase II inhibitors, MST-16 and VP-16, for refractory or relapsed non-Hodgkin's lymphoma.

It is known that the topoisomerase II inhibitors, MST-16 (sobuzoxane) and VP-16 (etoposide), are effective for the treatment of lymphoma. Five patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) were treated with a combination of oral MST-16 and VP-16 over a long period. Two patients had severely refractory NHL. The remaining 3 patients could not be treated with intensive chemotherapy because of severe organ dysfunction or a poor hematopoietic reserve. All 5 are alive and well after MST-16 and VP-16 treatment. MST-16 and VP-16 are effective for NHL when intensive chemotherapy is ineffective or contraindicated.

Administration, Oral↗