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M Kondoh

Publications and source records attributed to M Kondoh.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics of transcription-regulatory elements for gene expression from plasmid vectors in human trophoblast cell lines.

Nonviral gene delivery systems are useful for basic research in trophoblasts. In these systems, gene expression is regulated by a cassette of regulatory elements within the plasmid, and the transcriptional activity differs among cell lines. In the present study, we used BeWo and JAR human trophoblast cell lines to systematically compare the transcriptional activities of several expression cassettes and those of a control plasmid made up of a simian virus 40 (SV40) promoter, a polyadenylation (PA) signal, and an enhancer. We also found that insertion of intron elements enhanced transcriptional activities in the following order: intron A>hybrid beta-globin-immunoglobin intron>no intron. Of several PA signals tested including those from SV40, bovine growth hormone, and the minimal rabbit beta-globin, the latter had the highest transcriptional activities (3.9- and 26-fold over control plasmid in BeWo and JAR cells, respectively). Addition of a second enhancer increased the transcriptional activity in these cells. We also found that gene expression level can be controlled by selecting the expression cassette. These results should be useful for further transgene experiments in BeWo and JAR cells.

Cell Line, Tumor↗
PubMed2004

Comparison of transgene expression mediated by several Fiber-modified adenovirus vectors in trophoblast cells.

The transfer of genes of interest is a useful method for studying placental biology. Recombinant adenovirus (Ad) vector is an efficient vector for transgene expression. An interaction between the fiber of Ad and the coxsackievirus and adenovirus receptor on the cell membrane is the first step in infection. We previously developed fiber-modified Ad vectors and showed that they improved transgene activity in several cell lines when compared to wild-type vector. In the present study, we examined the ability of three fiber-modified Ad vectors to transduce human choriocarcinoma cell lines (JEG-3, JAR and BeWo) and rat trophoblast cell lines (Rcho-1, TR-TBT 18d-1 and TR-TBT 18d-2). We compared the transgene efficacy of wild-type Ad-L2 vector, Ad-RGD(HI)-L2 vector containing an Arg-Gly-Asp motif, Ad-K7(C)-L2 vector containing a 7-tandem lysine motif, and Ad-RGD(HI)K7(C)-L2 vector containing both motifs in the fiber. We used the luciferase gene as a reporter gene. In the human and rodent trophoblast cell lines, Ad-RGD(HI)-L2 had the greatest infectious potential, followed by Ad-RGD(HI)K7(C)-L2, Ad-K7(C)-L2 and Ad-L2. Compared to the amount of luciferase produced by wild-type vector, Ad-RGD(HI)-L2 mediated 8.1-fold the amount of luciferase in JEG-3 cells, 13.5-fold in JAR cells, 76.8-fold in BeWo cells, 5.0-fold in Rcho-1, 19.4-fold in TR-TBT 18d-1 and 15.0-fold in TR-TBT 18d-2. These results indicate that Ad-RGD(HI) is a potential recombinant Ad vector for transgene expression in some trophoblast cell lines.

Adenoviridae↗
PubMed2004

Induction of hepatic metallothionein synthesis by endoplasmic reticulum stress in mice.

Metallothionein (MT) is a small sulfhydryl-rich protein whose levels are elevated by various inducers of organelle stresses, such as nuclear stress (cisplatin), mitochondrial stress (antimycin A, 2,4-dinitrophenol) and lysosomal stress (paraquat). Although abnormal folding of protein in the endoplasmic reticulum (ER) causes ER stress, induction of MT synthesis by ER stress has never been investigated. In this study, we examined the induction of MT by an inducer of ER stress, tunicamycin (Tun), which induces ER stress by inhibiting N-linked glycosylation of protein in the ER. Administration of Tun (0.5-1.5 mg/kg, sc) increased hepatic MT levels in C57BL/6J mice (3.1-fold). The maximal increase in hepatic MT was observed 48-96 h after the administration of Tun (1.0 mg/kg). Expressions of MT-I, II and glucose-regulated protein 78 (Bip/GRP78), which is a molecular chaperone induced by ER stress, mRNA were also detected by administration of Tun. Thapsigargin (Thap), a generator of ER stress by inhibiting ER Ca(2+)-ATPase, also increased both hepatic MT levels and expression of MT-I and -II mRNA. The level of expression of Bip/GRP78 mRNA induced by Tun administration in MT-null mice was greater than that in wild-type mice. Taken together, these findings suggest that inhibitors of ER are potent inducers of MT.

Animals↗
PubMed2003

Antioxidant property of metallothionein in fasted mice.

Metallothionein (MT) is a low-molecular-weight and sulfur-rich protein that is induced by not only heavy metals but also physiological stresses such as fasting and restraint stresses. Although MT plays a role as a radical scavenger and a regulator of metabolism of metals, the biological function of MT induced by fasting stress has not been elucidated. In this study, we investigated the antioxidative role of MT in fasted mice. In fasted mice, the lipid peroxidation level of the liver was elevated by 24-h fasting stress, and pre-induction of hepatic MT by Zn diminished hepatic lipid peroxidation. Although 24-h fasting stress induced MT synthesis in the liver, other antioxidants such as catalase, manganese-superoxide dismutase (Mn-SOD), and glutathione peroxidase (GSHPx) were not activated in the liver. Moreover, the hepatic MT level was still elevated by fasting stress after seven cycles of repetition of alternate fasting and feeding every 24 h, but the activities of catalase, Mn-SOD and GSHPx were unchanged. These results indicate that MT induced by fasting stress plays partly as an antioxidant.

Animals↗
PubMed2003

Property of metallothionein as a Zn pool differs depending on the induced condition of metallothionein.

Metallothionein (MT) is a low-molecular-weight, cysteine-rich, heavy metal-binding protein with several putative physiological functions as a radical scavenger and a regulator of metabolism of Zn. Although the induction of hepatic MT by a wide range of stressors is a well-known phenomenon, little is known about the role of MT in stressful situations. Since MT regulates Zn metabolism, we investigated the differences between affinities of MT for Zn in various stressful conditions in this study. Divalent cadmium ions are capable of displacement of Zn from MT in vitro. Therefore, we assayed the binding of Zn to MT induced by various stimuli using in vivo administration of Cd. MT was induced by paraquat (PQ), a reactive oxygen generator, fasting stress and restraint stress. Apo-MT induced by them bound to Zn in vivo. Zn, which bound to MT induced by PQ, was displaced by the administration of Cd. However, Zn that had bound to MT induced by fasting stress and restraint stress was not displaced by Cd. Moreover, we assessed the in vivo affinity of Zn to MT induced by fasting stress under the condition of subchronic Cd exposure. Cd was administered to mice by subcutaneously implanted Alzet osmotic minipumps, which released constant amounts of Cd over a 14-day period. After 4 days, mice were fasted for 24 h and hepatic MT was examined. Interestingly, it was found that Zn had displaced Cd bound to MT. These findings indicate that the affinity of MT for Zn differs depending on the stimulus by which MT was induced. This is the first report on differences in the properties of MT depending on the stimulus used to induce MT.

Animals↗
PubMed2003

[Is adrenalectomy an indispensable part of nephrectomy? Results of a multivariate statistical analysis].

Since in the absence of clinically overt metastatic disease tumorous lesions within the adrenal gland are found in only 2-10% of cases, the majority of renal cell cancer patients are overtreated by adrenalectomy as an integral part of nephrectomy. The medical records of 847 patients undergoing adrenalectomy in combination with nephrectomy irrespective of the local extent of the primary tumor or the clinical stage at first diagnosis were reviewed to determine the reliability of currently available imaging modalities regarding the prediction of adrenal gland metastases. Several patient and tumor characteristics correlated with the presence of intra-adrenal metastases, and their prognostic value was determined by a multivariate logistic regression model. Metastatic spread into the adrenal gland was observed in 27 of 847 (3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site, preoperative abdominal CT scans were interpreted as false negative. During multivariate statistical analysis, only the presence of distant metastases, vascular invasion within the primary tumor, and multifocal growth of renal cell cancer within the tumor-bearing kidney were identified to independently predict the likelihood for the presence of intra-adrenal metastases. None of the patient or tumor characteristics evaluated reliably predicted the likelihood for the presence of adrenal metastases in patients without evidence of disseminated metastatic spread. As we believe and as the current investigation demonstrates, routine adrenalectomy should not be recommended in cases of preoperatively normal radiological examinations.

Adrenal Gland Neoplasms↗
PubMed2002

Surgical bladder preserving strategies in the treatment of muscle-invasive bladder cancer.

Single modality bladder-sparing therapy for muscle-invasive bladder cancer, including transurethral resection (TUR), partial cystectomy, systemic chemotherapy or radiotherapy, have been demonstrated to result in insufficient local control of the primary tumour, as well as decreased long-term survival in the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitise tumour tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder-sparing approaches are costly, and require close co-operation between different clinical specialists as well as careful follow-up. The good long-term results that are observed after cystectomy and the creation of an orthotopic neobladder make the substantial advantage of a bladder preservation strategy questionable when the patient's quality of life is addressed. Additionally, bladder-sparing therapy-related side effects might result in an increased morbidity and mortality in those patients who need to undergo surgery due to recurrent or progressive disease. Multimodality bladder-sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder cancer.

Humans↗
PubMed2001

Specific induction of metallothionein synthesis by mitochondrial oxidative stress.

Metallothionein (MT), a sulfhydryl-rich protein, may be increased by administration of a variety of agents, including metals, cytokines and oxidative stress agents. Mitochondria are a major source of reactive oxygen species, but antioxidant systems against mitochondrial free radicals are not fully understood. In this study, we examined the induction of MT synthesis by administration of mitochondrial-specific reactive oxygen generators such as antimycin A (AA), an electron transfer inhibitor, and 2,4-dinitrophenol (DNP), an uncoupling agent. Subcutaneous administration of AA to mice significantly increased the hepatic MT concentration in a dose- and time-dependent manner. AA slightly elevated glutathione peroxidase (GSHPx) activity, but the rate of increase in GSHPx (1.3-fold) was smaller than that in MT (11.8-fold). Other antioxidants such as catalase, manganese-superoxide dismutase (Mn-SOD), copper/zinc-superoxide dismutase (Cu/Zn-SOD) and GSHPx were not activated by AA treatment. Moreover, administration of DNP induced the synthesis of MT in the liver. Although DNP slightly elevated Mn-SOD activity, the rate of increase in Mn-SOD (1.3-fold) was smaller than that in MT (3.7-fold). Other antioxidants such as catalase, Cu/Zn-SOD and GSHPx were not activated by DNP treatment. These data suggest that MT plays a major role in protection against oxidative stress induced in mitochondria.

2,4-Dinitrophenol↗
PubMed2001

Unifying the relationships of species richness to productivity and disturbance.

Although species richness has been hypothesized to be highest at 'intermediate' levels of disturbance, empirical studies have demonstrated that the disturbance-diversity relationship can be either negative or positive depending on productivity On the other hand, hypothesized productivity diversity relationships can be positive, negative or unimodal, as confirmed by empirical studies. However, it has remained unclear under what conditions each pattern is realized, and there is little agreement about the mechanisms that generate these diverse patterns. In this study, I present a model that synthesizes these separately developed hypotheses and shows that the interactive effects of disturbance and productivity on the competitive outcome of multispecies dynamics can result in these diverse relationships of species richness to disturbance and productivity The predicted productivity diversity relationship is unimodal but the productivity level that maximizes species richness increases with increasing disturbance. Similarly, the predicted disturbance diversity relationship is unimodal but the peak moves to higher disturbance levels with increasing productivity Further, these patterns are well explained by the opposite effects of productivity and disturbance on competitive outcome that are suggested by the change in community composition along these two environmental gradients: higher productivity favours superior competitors while higher disturbance levels favour inferior competitors.

Animals↗
PubMed2001

Fundamental study of the behavior of chlorine during the combustion of single RDF.

A fundamental study of the combustion characteristics and the de-HCl behavior of a single refuse-derived fuel (RDF) pellet was carried out to explain the de-HCl phenomena of RDF during fluidized bed combustion and to provide data for the development of high efficiency power generation technology using RDF. In this research, combustion and pyrolysis experiments were carried out in an electrical furnace using a series of model and actual RDF samples. The de-HCl capability of Ca(OH)2 in RDF was evaluated by measuring the emission fraction of HCl in the flue gas and the capture fraction of Cl in the residue. It was found that the capture fraction of Cl components in the residue increased from 0 to nearly 70% when the molar ratio of Ca/Cl was changed from 0 to around 13. Apparently, the capture fraction also decreased with increasing oxygen concentration in the feed gas. The devolatilization process of RDF was confirmed to be a very important part of de-HCl process. The effect of temperature profile of the RDF pellet on the de-HCl process, as it varies with the heating rate of RDF and the oxygen concentration in the vicinity of the sample, is discussed.

Air Pollution↗
PubMed2001

[Renal autotransplantation in a patient with acute renal infarction following surgery for a dissecting aneurysm].

A 58-year-old woman experienced a sudden onset of severe chest and back pain and thus visited our center in October 1999. Contrast-enhanced computed tomography (CT) revealed a Stanford type A acute aortic dissection. The CT also demonstrated a 50 mm ascending aorta and dissection from the ascending aorta via the abdominal aorta to the level of the left renal artery. The perioperative transesophageal echocardiogram showed an intimal tear in the ascending aorta without valvular abnormality. Therefore, we performed graft replacement of the ascending aorta. On the first postoperative day, she developed oliguria and showed a sudden rise in serum creatinine (Cr) and blood urea nitrogen (BUN) levels, necessitating hemodialysis. She required daily hemodialysis or hemofiltration for twenty days. Thereafter, renal function recovered and dialysis was no longer performed. However, on postoperative day 26, the patient complained of sudden lumber pain. Unheralded oliguria was associated with worsening renal function. A CT scan at this point revealed infarction of the left kidney. During surgery, the left kidney was excised for heterotopic autotransplantation. Extensive thrombosis within a true lumen of the left renal artery was revealed. Following removal of the thrombus and perfusion with heparinized cold saline, renal autotransplantation to a heterotopic site in the pelvis were performed. Although the patient required hemodialysis for five days, renal function recovered gradually. She was discharged five months later. In our experience, it appears that heterotopic renal autotransplantation by which normal arterial perfusion distal to the dissection is reestablished is a good therapeutic option for reperfusion of the ischemic kidney compromised by a progressive dissection of the thoracoabdominal aorta.

Aortic Dissection↗
PubMed2001

Integrated biological and chemical control of damping-off caused by Rhizoctonia solani using Bacillus subtilis RB14-C and flutolanil.

Bacillus subtilis RB14-C was isolated as a potential biological agent to control the occurrence of various plant diseases. Integrated control of damping-off in tomato plants caused by Rhizoctonia solani was carried out in pots using B. subtilis RB14-C and chemical pesticide, flutolanil. The growth of RB14-C was the same in both the flutolanil-containing and the flutolanil-free media, indicating the resistance of RB14-C to flutolanil. Although the productivity of surfactin decreased to one-third in the flutolanil-containing medium, compared with that in the flutolanil-free medium, the productivity of iturin A which is mainly associated with the suppressive ability of RB14-C against plant pathogens was unaffected. The integration of RB14-C and flutolanil reduced the amount of flutolanil used to one-fourth of that of the single use of flutolanil, with the same efficacy of reducing disease occurrence.

Journal Article↗
PubMed2000

Cytokines and T-cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets of T cells and in T cells expressing several T-cell receptor (TCR) V beta+cells, perhaps representing V beta-specific T-cell activation by MRSA-derived superantigens (Kidney Int 1995; 47: 207-216). In this study we examine cytokine levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA-associated GN. METHODS: Twenty-two patients with MRSA infection who later developed GN caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals. RESULTS: Among peripheral lymphocytes, the frequency of T cells expressing several TCR V betas, especially V beta 5-family TCR, was higher in the GN group than in both the non-GN group and the normal healthy control group. GN patients also showed increased serum levels of several cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in the GN group. CONCLUSION: These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Adult↗
PubMed2000

Growth inhibition of human leukemia HL-60 cells by an antisense phosphodiester oligonucleotide encapsulated into fusogenic liposomes.

We report here the antisense effect of phosphodiester oligodeoxynucleotide (D-ODN) using fusogenic liposomes (FL) as its carrier. FL has envelope proteins of the Sendai virus within its membrane and introduces its contents directly and efficiently into cytosol by means of the virus-cell fusion mechanism. Using antisense (AS) D-ODN 15-mer complementary to the c-myc proto-oncogene mRNA, including the translation initiation codon site, we analyzed the growth of HL-60 cells by [3H]-thymidine uptake. AS-ODNs encapsulated in FL inhibited the growth by about 70% that of the control HL-60 cells at 2.48 microM. In contrast, sense and scramble D-ODNs encapsulated in FL showed no effect of the growth of HL-60 cells at the same concentration. Even at 50 microM, free form D-ODNs did not show any effect. These results suggest that FL is potentially a useful delivery vehicle for oligonucleotide-based therapeutics, and that D-ODN may be a likely candidate for oligodeoxynucleotides when an efficient delivery system is used.

Base Sequence↗
PubMed2000

Synthesis of pironetin and related analogs: studies on structure-activity relationships as tubulin assembly inhibitors.

Pironetin (1) and demethylpironetin (2) are potent inhibitors of tubulin assembly. They arrested the mammalian cell cycle in M-phase and showed antitumor activity against a murine tumor cell line, P388 leukemia, transplanted in mice. To investigate the chemical and biological properties of 1, we synthesized several derivatives and investigated the structure-activity relationships. All synthesized derivatives decreased biological activities, such as inhibition of cell cycle progression, and disruption of the microtubule network in situ. The most drastic decrease was observed in 6, 8 and 10. These results suggested that alpha,beta-unsaturated lactone, chirality at the 7-position bearing a hydroxyl group and the terminal portion of the alkyl chain are important for microtubule inhibitory activity of pironetins.

Animals↗
PubMed2000

[A case of 19th year pulmonary metastasis after radical mastectomy for breast cancer].

A 72-year-old woman was admitted to our hospital for further evaluation of a abnormal shadow in left middle lung field. The patient had undergone right mastectomy for infiltrating ductal carcinoma 19 years ago. She had no symptom, but had a time of mass X-ray screening this year. Chest CT finding showed a nodule 2 cm in diameter with slight irregular margin in S6 of left lung. We couldn't determine preoperatively that this tumor was a metastatic lesion or a primary lung cancer. And first, tumor was taken out for intraoperative frozen section diagnosis. Pathologist didn't diagnose whether this tumor was a metastatic or primary. So, we performed left lower lobectomy and mediastinal lymphadenectomy. On postoperative histopathologic finding lung cancer resembled well previous breast cancer. In immunohistochemical study cancer cells from lung and breast of the patient were respectively positive for anti Estrogen Receptor (ER) and anti Gross Cystic Disease Fluid Protein-15 (GCDFP-15). In conclusion lung cancer was diagnosed as a metastatic lesion from breast cancer 19 years ago. The patient has been well 2 years postoperatively without recurrence. In this case immunohistochemical examination was very useful for differentiation metastatic lesion and primary one.

Aged↗