A case of huge gastric varices successfully treated with endoscopic injection sclerotherapy with occlusion of both supplying and draining veins with balloons.
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Aged↗
Biomedical subjects
Y Saeki
Publications and source records attributed to Y Saeki.
Delayed embryonic development of mouse masseter muscle correlates with delayed MyoD family expression.
While the masseter muscle is known to have several unique developmental characteristics as compared with other skeletal muscles, little is known about its myogenesis. Thus, we examined the expression of myogenic marker and of myoD family gene mRNA from embryonic day (E) 11 to birth. The obtained results were compared with our earlier results of the mouse tongue muscle, which is also involved in oral functions. The mRNA quantities were determined by means of the reverse-transcription and competitive-polymerase chain-reaction techniques. The expression of myogenic marker mRNA indicated that differentiation and maturation in the masseter began at E13 as in the tongue, and were not yet completed at birth, although they were completed in the tongue. The expression of myoD, myogenin, and myf5 mRNA peaked later in the masseter (E17) than in the tongue (E13). The expression of MRF4 mRNA began later in the masseter (E15) than in the tongue (E13). These results suggest that the delayed expression of the myoD family genes in the masseter correlates with delayed differentiation and maturation, probably due to the later functional requirements of the masseter than of the tongue.
Animals↗
Maintaining remission of lupus erythematosus profundus (LEP) with cyclosporin A.
We report a young female patient with recurrent lupus erythematosus profundus (LEP) who has successfully maintained remission of LEP with cyclosporin A (CsA), although conventional treatments such as systemic corticosteroids (low-dose), dapsone, and other immunosuppressive drugs (azathiopurine, cyclophosphamide) could not maintain remission.
Adolescent↗
Role of prostaglandin E2 and leukotriene B4 in skin reaction induced by transdermal application of propranolol.
Dermal application of propranolol (PRL) induced formation of erythema and edema, and pseudoeosinophil infiltration in epidermis and dermis at the application site in guinea pigs. We investigated the production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) at the application site of PRL and the role of these inflammatory chemical mediators in the occurrence of the skin reactions. PGE2 was found to be produced at the application site slightly after the accumulation of PRL released from the adhesive bandage in the patch test, and the amount of PGE2 increased continuously, with a peak value obtained at 24 h after application. The time-course changes resembled those of delta a* value, the index of erythema formation determined by colorimetric measurement, and edema formation. The production of PGE2 by dermal application of PRL was suppressed by local pretreatment with dexamethasone or indomethacin. However, no notable production of LTB4 was observed at the application site of PRL.
Administration, Cutaneous↗
Adsorption of oral bacteria to porous type calcium carbonate.
The purpose of this study was to investigate the adsorption of [3H]-thymidine labeled oral microorganisms to porous type calcium carbonate (PCC) beads in a buffer containing human parotid saliva and to PCC combined chewing gum sheets. Adsorption rates of Streptococcus sobrinus B13 and 6715, Streptococcus mutans MT8148R and Actinomyces naeslundii T14V with PCC were significantly higher than those with calcium carbonate (CC) beads (p < 0.01). Adsorption rates of S. sobrinus, S. mutans and A. naeslundii with PCC combined chewing gum were significantly higher than those with CC combined chewing gum (p < 0.01). The present results suggested that the chewing gum containing PCC may be able to exclude oral bacteria, including cariogenic and periodontopathic bacteria, for prevention of dental caries and periodontal disease.
Actinomyces↗
Participation of a MEK-independent pathway in MAP kinase activation and modulation of cell growth in mouse hepatoma cell lines.
The mechanism of cell growth was investigated in GIT medium-supplemented in vitro assay using high and low metastatic mouse hepatoma cell sublines, G-5 and G-1, respectively. G-5 cells exhibited high growth rate compared to G-1 cells. The PI3-kinase inhibitor LY294002 and P70 S6 kinase inhibitor rapamycin partially blocked both G-1 and G-5 cell growth, suggesting that these two kinases are involved in hepatoma cell growth. In contrast, the MEK1 inhibitor PD98059 partially blocked G-5 cell growth but not G-1 cell growth. MAP kinases (MAPK) in both G-1 and G-5 cells were indistinguishably phosphorylated, yet MEK-dependent MAPK activation was observed only in G-5 cells. In G-1 cells, MAPK was phosphorylated in a manner not connected to MEK activation. Thus, the low degree of cell growth in G-1 cells was attributable to disruption of the MEK-dependent MAPK cascade. However, the molecular mechanism whereby MAPK phosphorylation does not parallel MAPK activation in G-1 cells remains unknown. Here, we suggest that there may be an as yet unidentified MAPK phosphorylation pathway in malignantly transformed cells, which may affect in vivo cell growth and metastatic capacities of cancers.
Animals↗
[Advanced methods for the manipulation of herpesvirus genomes].
The Herpesviridae are a family of viruses which have a large genome of linear, double-stranded DNA (> 120 kb). It has been quite difficult to clone and modify herpesvirus genomes because of their large sizes. Recently, several groups of investigators demonstrated successful cloning of infectious herpesvirus genomes as bacterial artificial chromosomes (BACs). In this review, I describe the recent development of methods to modify the cloned viral genomes. The methods are: (i) homologous recombination in E. coli which allows targeted mutagenesis of any specific viral sequence, and (ii) mutagenesis which allows random modification of entire viral genomes. Both methods should facilitate both the study of herpes viruses and the development of herpesvirus-based vector system.
Cloning, Molecular↗
[Herpes simplex type-1 virus-based vectors for gene therapy].
Recent advances in recombinant nucleic acid technologies and the understanding of the molecular biology of diseases provide the basis for gene therapy's ability to impact on the clinical practice of medicine. Herpes simplex virus type 1 (HSV-1) has features that make it suitable as a vector for gene therapy. These properties include: 1) wide host range and high efficiency of gene transfer; 2) large transgene capacity which is provided by deletion of genes unnecessary for viral replication; 3) unique ability of entering a state of latency in neurons; 4) specific oncolytic effect of some mutants by deletion of certain early genes. Three types of vectors designed for gene therapy have been developed from this virus, termed replication-defective vectors, replication-conditional vectors and amplicon vectors. In this review, we describe the recent advances in HSV-1-based vector systems and their applications for gene therapy.
Animals↗
The effect of foot-bath with or without the essential oil of lavender on the autonomic nervous system: a randomized trial.
OBJECTIVES: This study was designed to investigate the effect of foot-bath with or without the essential oil of lavender on the autonomic nervous system. DESIGN: Randomized crossover controlled study. SETTING: Nursing college, Nagano, Japan. INTERVENTION: Young women sat with their feet soaked in hot water for 10 minutes with and without the essential oil. OUTCOME MEASURES: An electrocardiogram, finger tip blood flow and respiratory rate were recorded. Autonomic function was evaluated using spectral analysis of heart rate variability. RESULTS: The foot-bath caused no changes in heart or respiratory rates, but produced a significant increase in blood flow. Using spectral analysis, the parasympathetic nerve activity increased significantly during the both types of foot-bath. In the case of the foot-bath with the addition of essential oil of lavender, there were delayed changes to the balance of autonomic activity in the direction associated with relaxation. CONCLUSION: A hot foot-bath and oil of lavender appear to be associated with small but significant changes in autonomic activity.
Adult↗
IL-6 plays a crucial role in the induction phase of myelin oligodendrocyte glucoprotein 35-55 induced experimental autoimmune encephalomyelitis.
We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active induction of EAE, but that the treatment of those mice with IL-6 during the preclinical phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1beta, IL-2, TNF-alpha, and IFN-gamma in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the induction phase, but might have little influence on the effector phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-gamma production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Thl to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the induction phase of EAE by modulating Th1/Th2 balance.
Animals↗
Dominant and shared T cell receptor beta chain variable regions of T cells inducing synovial hyperplasia in rheumatoid arthritis.
Previously, we demonstrated the presence of at least two distinct subpopulations of patients with rheumatoid arthritis (RA) employing a cell-transfer experiment using severe combined immunodeficient (SCID) mice. One group of patients, whose T cells derived from the rheumatoid joints, induced synovial hyperplasia (SH) in the SCID mice (the positive group). The other group did not display the induction of SH (the negative group). TCR/Vbeta gene usage analysis indicated that some dominant T cell subpopulations were oligoclonally expanding only in the rheumatoid joints, and not in the periphery of the patients of the positive group. Moreover, these T cell subpopulations were not seen in the joints of patients in the negative group or in non-RA patients. In addition, the preferential uses of certain TCR/Vbetas (Vbeta8, Vbeta12, Vbeta13, and Vbeta14) genes were demonstrated in these T cells. In this study, to investigate whether these T cells are driven by a certain antigen(s), the third complementarity determining regions (CDR3s) of TCR/Vbeta, especially Vbeta8 and Vbeta14 PCR products, were cloned and sequenced. As a result, a dominant CDR3 sequence, CASS-PRERAT-YEQ, was found in Vbeta14+ T cells from the rheumatoid joint of a patient (Patient 1) of the positive group with a Vbeta14 skew. The identical CDR3 sequence also predominated in Vbeta14+ T cells from the rheumatoid joint of another patient (Patient 7) of the positive group with a Vbeta14 skew. In addition, in the patients (Patients 4, 7, 8) of the positive group with a Vbeta8 skew, other dominant CDR3 sequences, CASS-ENS-YEQ and CASS-LTEP-DTQ, were found as in the case of Vbeta14. However, no identical CDR3 sequences were detected dominantly in the joints of the patients in the negative group or in non-RA patients. A Vbeta14+ T cell clone (TCL), named G3, with the identical CDR3 sequence, CASS-PRERAT-YEQ, was isolated successfully from Patient 1, and cell transfer of G3 with autologous irradiated peripheral mononuclear cells induced SH in the SCID mice. Taken together, these results suggest that T cells inducing SH, thought to be pathogenic for RA, might be driven by a certain shared antigen(s).
Amino Acid Sequence↗
Ribosome-associated protein LBP/p40 binds to S21 protein of 40S ribosome: analysis using a yeast two-hybrid system.
The ribosome-associated protein LBP/p40, which was originally named after "laminin binding protein precursor p40," is distributed on the cell surface as laminin binding protein p67 (LBP/p67), in the nucleus, and on 40S ribosomes. In a broad range of eukaryotes, the localization of LBP/p40 on the 40S ribosome is well conserved. Two yeast homologs of LBP/p40 are believed to be essential for cell viability and each gene product probably corresponds to the assembly and/or stability of the 40S ribosomal subunit. The precise role of LBP/p40 in translation, however, remains to be elucidated, especially in higher eukaryotes. In this report, we used a yeast two-hybrid screening method to isolate molecules associated with human LBP/p40 protein on ribosomes. We found that the 40S ribosomal protein S21 was tightly bound with LBP/p40 in this yeast two-hybrid system and in in vitro analysis. Further, we discovered that the association required a broad region of the LBP/p40 amino acid sequence, which corresponds to the highly conserved region of LBP/p40 homologs among eukaryotes.
5' Untranslated Regions↗
Delayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficient mice.
OBJECTIVE: To investigate the roles of interleukin-6 (IL-6) in the pathogenesis of rheumatoid arthritis (RA) by studying its effect on murine collagen-induced arthritis (CIA). METHODS: IL-6-deficient (IL-6-/-) mice with a genetic background of susceptibility to CIA were generated by backcrossing them with DBA/1J mice for 8 generations. Clinical and immunologic features were compared between these mice and IL-6 wild-type (IL-6+/+) littermates with CIA. RESULTS: Serum IL-6 levels increased during the development of CIA in IL-6+/+ mice. Two prominent peaks were observed. The first was coincident with the onset of arthritis, and the second one was observed during exacerbation of the disease. The onset of arthritis in IL-6-/- mice was delayed for 2 weeks compared with that in IL-6+/+ mice, and the severity of arthritis, as indicated by the arthritis score, remained significantly lower in IL-6-/- mice during the entire followup period (14 weeks), although all IL-6-/- mice developed definite arthritis as did the IL-6+/+ mice. Histologic severity was also reduced in IL-6-/- mice. In addition, radiologic changes such as osteopenia and bone erosion were reduced significantly in these animals. Both humoral and cellular responses to type II collagen (CII) in IL-6-/- mice were reduced to about half those in IL-6+/+ mice. In addition, enhanced production of IL-4 and IL-10 in response to concanavalin A stimulation was observed in IL-6-/- mice. CONCLUSION: IL-6 plays an important role in the development of CIA, and both suppression of specific immune responses to CII and a tendency to a shift toward a Th2 cytokine profile might contribute in part to the attenuation of CIA in IL-6-/- mice. These findings suggest that blockade of IL-6 might be beneficial in the treatment of RA.
Animals↗
Adaptation of guinea-pig superficial masseter muscle to an increase in occlusal vertical dimension.
To study the effect of increased occlusal vertical dimension on the fibre phenotypes of the superficial masseter muscle, the composition of myosin heavy-chains (MHC), myosin light-chains (MLC) and tropomyosin was investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis in conjunction with densitometric analysis in normal (control) and bite-opened (5.7 mm increase in the vertical dimension for 1 week) guinea-pigs. The superficial masseter contained two fast-type MHC isoforms, II-1 and II-2, in both the bite-opened and control groups; their relative content (mean+/-SD, n = 7) was 47.8+/-2.9% and 52.2+/-2.9%, in the bite-opened and 44.4+/-3.0% and 55.6+3.0% in control preparations, indicating no significant (p>0.05) changes in MHC composition in association with the bite opening. On the other hand, significant differences in MLC and tropomyosin composition were found between the two preparations. Although the MLC consisted of three components, LC1f, LC2f and LC3f, in both preparations, their relative content (mean+/-SD, n = 7) was 37.1+/-2.4%, 49.6+/-1.6% and 13.2+/-3.2%, respectively, in the bite-opened and 28.1+/-3.1%, 50.9+/-1.6% and 21.0+/-3.5% in the control preparations, indicating that the bite opening induced a significant (p < 0.0001) increase in the relative content of LC1f at the expense of that of LC3f. Although the tropomyosin consisted of two components, TM-alpha and TM-beta, in both preparations, their relative content (mean+/-SD, n = 7) was 91.8%+/-1.9% and 8.2+/-1.9%, respectively, in the bite-opened and 95.9+/-0.7% and 4.1+/-0.7% in the control preparations, showing a significant (p < 0.001) increase in the relative content of TM-beta in relation to the bite opening. These results indicate that in guinea-pigs an increase in occlusal vertical dimension for 1 week changes the composition of MLC and tropomyosin, with no significant change in MHC, in the masseter muscle. These changes might be required to meet altered functional demands.
Adaptation, Physiological↗
Gene therapy using HVJ-liposomes: the best of both worlds?
A new concept for the development of novel vectors is to overcome the limitations of individual vectors by combining them. The HVJ-liposome was developed by combining liposomes with fusion proteins derived from the hemagglutinating virus of Japan (HVJ), also known as Sendai virus. Gene transfer in vivo using this delivery system can be repeated because it is much less immunogenic and cytotoxic than other viral-vector systems. By coupling the Epstein-Barr virus (EBV) replicon apparatus with HVJ-liposomes, transgene expression can be sustained in vitro and in vivo. In animal models, this system has shown promise for several diseases, including cancer and cardiovascular disease.
Animals↗
Long-term follow-up of the changes in circulating cytokines, soluble cytokine receptors, and white blood cell subset counts in patients with rheumatoid arthritis (RA) after monoclonal anti-TNF alpha antibody therapy.
To investigate the mechanism of the long-lasting efficacy of chimeric monoclonal anti-TNFalpha antibody (cA2) therapy for rheumatoid arthritis (RA), eight patients with refractory RA were treated with a single infusion of cA2 and the changes in circulating cytokines (IL-1, IL-6, TNFalpha, and IL-10), soluble cytokine receptors (TNF-RI, RII, and sIL-6R) and peripheral white blood cell (WBC) subset counts were followed up long-term (12 weeks) after cA2 therapy in them. Significant clinical responses (>20% improvement according to Paulus' criteria) were observed just after cA2 infusion and lasted more than 4 weeks in all patients, as reported elsewhere. Moreover, five of the eight patients showed prolonged clinical responses (>12 weeks). The elevated serum IL-6 and sTNF-RI (or RII) levels before treatment rapidly decreased after treatment. The serum IL-10 levels also significantly elevated before treatment. The elevations of serum IL-10 levels were augmented after treatment and stayed higher than the baseline in four patients with prolonged clinical responses. No significant TNFalpha, IL-1alpha and -beta, or sIL-6R were detected in the sera of the patients before treatment and during the whole study period. On the other hand, peripheral lymphocytes as well as total WBC and neutrophils increased for 4 weeks after treatment. However, thereafter, only the lymphocyte count decreased gradually and stayed below the baseline long-term (12 weeks). FACS analysis revealed the predominance of T lymphocytes in the decrease in lymphocyte counts. These results suggest that the augmentation of IL-10 production and the decrease in T cells might partly contribute to the long-lasting efficacy of cA2 treatment in RA.
Adult↗
Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progression.
To elucidate the role of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in tumour angiogenesis and malignant progression, an expression vector harboring human VEGF cDNA was stably transfected into three human cancer cell lines with poor VEGF productivity. Though their in vitro growth rate and intrinsic productivity of another angiogenic factor, basic fibroblast growth factor (bFGF), were not changed by transfection, those clones with higher VEGF production were endowed with tumorigenic and angiogenic potentials as follows: firstly, nontumorigenic, lung carcinoma QG90 cells having lower bFGF productivity acquired tumorigenicity as well as significant in vivo angiogenesis-inducing ability, secondly, tumorigenic colorectal carcinoma RPMI4788 cells having higher potency for bFGF production could form more vascularized solid tumour with faster growth rate and thirdly, oestrogen-dependent breast carcinoma MCF-7 cells, which did not produce detectable bFGF, acquired tumorigenicity even in the absence of oestrogen and the solid tumour growth rate was remarkably enhanced, accompanied with increased vascularization, in the presence of oestrogen. These results suggest that tumour progression closely depends on angiogenesis, and VEGF significantly contributes to malignant progression of a variety of tumour cells through its potent angiogenic activity, independent on the bFGF productivity of tumour cells.
Animals↗
Single-step conversion of cells to retrovirus vector producers with herpes simplex virus-Epstein-Barr virus hybrid amplicons.
We report here on the development and characterization of a novel herpes simplex virus type 1 (HSV-1) amplicon-based vector system which takes advantage of the host range and retention properties of HSV-Epstein-Barr virus (EBV) hybrid amplicons to efficiently convert cells to retrovirus vector producer cells after single-step transduction. The retrovirus genes gag-pol and env (GPE) and retroviral vector sequences were modified to minimize sequence overlap and cloned into an HSV-EBV hybrid amplicon. Retrovirus expression cassettes were used to generate the HSV-EBV-retrovirus hybrid vectors, HERE and HERA, which code for the ecotropic and the amphotropic envelopes, respectively. Retrovirus vector sequences encoding lacZ were cloned downstream from the GPE expression unit. Transfection of 293T/17 cells with amplicon plasmids yielded retrovirus titers between 10(6) and 10(7) transducing units/ml, while infection of the same cells with amplicon vectors generated maximum titers 1 order of magnitude lower. Retrovirus titers were dependent on the extent of transduction by amplicon vectors for the same cell line, but different cell lines displayed varying capacities to produce retrovirus vectors even at the same transduction efficiencies. Infection of human and dog primary gliomas with this system resulted in the production of retrovirus vectors for more than 1 week and the long-term retention and increase in transgene activity over time in these cell populations. Although the efficiency of this system still has to be determined in vivo, many applications are foreseeable for this approach to gene delivery.
3T3 Cells↗