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T Honda

Publications and source records attributed to T Honda.

At least 109 records · Page 6Linked to original sources
PubMed2001

Deficiency of caspase-3 in MCF7 cells blocks Bax-mediated nuclear fragmentation but not cell death.

Caspase-3 plays a critical role in a proteolytic cascade within the apoptosis signal pathway; this enzyme is commonly activated by numerous death signals and cleaves a variety of important cellular proteins. Using caspase-3-deficient MCF7 cells and clones stably transfected with the caspase-3 gene (MCF7/Casp3), we evaluated the role of caspase-3 in Bax-induced apoptosis. Bax overexpression induced cell death in both parental MCF7 cells and MCF7/Casp3 cells. The introduction of the caspase-3 gene did not change the rate of cell death. Caspase-3-deficient parental MCF7 cells, however, failed to undergo morphological nuclear and DNA fragmentation, whereas MCF7/casp3 cells displayed intact nuclear dismantling and DNA fragmentation. Caspase-3 deficiency, however, did not affect Bax-induced levels of poly(ADP-ribose) polymerase cleavage, caspase-6 activation, and lamin B cleavage. Together, these results suggest that a deficit in caspase-3 is not sufficient to block Bax-induced cell death.

Apoptosis↗
PubMed2001

[A case of IgA2-lambda type M-protein that IgA concentration differs from the values of M-protein by serum protein electrophoresis].

We report an IgA-lambda type M-protein in which the IgA concentration differed from the values of M-protein by serum protein electrophoresis found in a 53-year-old man with multiple myeloma. The M-protein value as determined by serum protein electrophoresis was 6,170 mg/dl. However, the serum IgA concentration was 3,052 mg/dl by turbidimetric immunoassay. Immuno-fixation electrophoresis using IgA subclass antisera revealed that this M-protein was the IgA2-lambda type. Western blotting analysis showed that the IgA2 molecules were composed of two approximately 68 kDa alpha 2 chains and two 28 kDa lambda chains. In addition the free lambda chain band was detected at the position of 28 kDa without 2-mercaptoethanol(2-ME) even though the patient IgA was purified. Since it is known that IgA2m(1) allotype easily release light chains from the IgA molecules in SDS-PAGE without 2-ME, we speculated that in this patient the IgA was the IgA2m(1) allotype. After peripheral blood stem cell transplantation(PBSCT), immunofixation electrophoresis of the patient serum revealed not only the bands of IgA2-lambda type M-protein, but also three bands of IgG1-kappa type M-protein in the gamma region.

Blood Protein Electrophoresis↗
PubMed2001

[Clinical significance of plasma atrial and brain natriuretic peptide levels during hemodialysis in hemodialysis patients with old myocardial infarction].

OBJECTIVES: The plasma levels of atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) are useful to evaluate left ventricular function in patients with old myocardial infarction(OMI). This echocardiographic study examined the clinical importance of the measurement of ANP and BNP in patients with OMI undergoing hemodialysis. METHODS: ANP and BNP levels were measured before and after hemodialysis in 36 patients with OMI and 42 patients without ischemic heart disease as controls(control group). Echocardiography was performed after hemodialysis. The patients with OMI were classified into two groups according to left ventricular percentage fractional shortening(% FS): Normal(OMI-N) group with %FS > or = 30%(n = 19) and low (OMI-L) group with %FS < 30%(n = 17). RESULTS: The ANP, BNP levels and BNP/ANP ratio before and after hemodialysis were significantly higher in the OMI-L group than in the other groups. BNP level was significantly inversely correlated with %FS(r = -0.60, p < 0.05) and correlated with E wave and E/A, in mitral inflow only in the OMI-L group. The decrease in BNP level during hemodialysis was significantly greater in the OMI-L group than in the other groups, but not in ANP level. CONCLUSIONS: These findings suggest that ANP and BNP levels are increased in patients with left ventricular dysfunction undergoing hemodialysis compared to those with normal left ventricular function. ANP level is convenient for decision of suitable dry weight. In contrast, BNP level that correlated inversely with impairment of left ventricular function is a more sensitive index of left ventricular function than ANP in patients with OMI undergoing hemodialysis.

Atrial Natriuretic Factor↗
PubMed2001

[A case of ovarian cancer with metastatic tumor in the liver with paclitaxel and carboplatin systemic chemotherapy was very effective].

An 82-year-old woman was admitted to the Dept. of Obstetrics and Gynecology, Yamanashi Medical University to try to identify the origin of a liver metastatic tumor. CT examination revealed a small tumor located adjacent to the uterine cervix in a cul-de-sac. With biopsy using MR, it was clearly shown histologically that the origin of the tumor was the ovary. Systemic chemotherapy with paclitaxel and carboplatin was selected as the most reasonable treatment for this case because of the patient's age. After 6 courses of this chemotherapy, the tumor in the cul-de-sac disappeared and the tumor in the liver decreased markedly. Furthermore, no severe side effects were seen during this treatment. This result indicated that systemic chemotherapy with paclitaxel and carboplatin is effective and safe in cases of advanced ovarian cancer.

Adenocarcinoma↗
PubMed2001

[Cerebral autoregulation during sevoflurane or isoflurane anesthesia: evaluation with transient hyperemic response].

We investigated dynamic cerebral autoregulation during N2O-O2/fentanyl anesthesia (baseline) plus 1.0 and 2.0 minimum alveolar anesthetic concentrations (MAC) of sevoflurane or isoflurane anesthesia in 14 patients undergoing non-neurosurgical operation. Cerebral blood flow velocity in the right middle cerebral artery (Vmca) was measured continuously using transcranial Doppler ultrasonography. At normocapnia, dynamic cerebral autoregulation was tested by transient hyperemic response (a response of Vmca after a brief compression of the ipsilateral common carotid artery). For quantitative comparisons, ratio of systolic Vmca before, to immediately after compression (THRR) was calculated. Values of THRR were 1.14 +/- 0.03 (mean +/- SD), 1.15 +/- 0.04, and 1.12 +/- 0.03 during baseline, 1.0, and 2.0 MAC sevoflurane anesthesia, respectively. THRR was not significantly different among the 3 conditions. In contrast, THRR values were 1.17 +/- 0.03, 1.07 +/- 0.02, and 1.01 +/- 0.01 during baseline, 1.0, and 2.0 MAC isoflurane anesthesia, respectively. THRR was significantly attenuated in a dose dependent manner during isoflurane anesthesia. These results indicate that dynamic cerebral autoregulation is preserved during 2.0 MAC sevoflurane anesthesia, but not during 1.0 MAC isoflurane anesthesia.

Adult↗
PubMed2001

[A case of primary leiomyosarcoma of the pulmonary artery].

A 74-year-old woman was admitted to our hospital because of right chest pain. The chest radiograph showed right hilar pulmonary artery dilatation. A mass exhibiting low intensity in T1-weighted images and high intensity in T2-weighted images was disclosed in the right pulmonary artery. Because of its clinical course and the MRI findings, the mass was thought to be tumorous tissue, and so pneumonectomy was performed. Leiomyosarcoma was diagnosed from the histological findings. Primary artery sarcoma is rare and the prognosis is considered to be extremely poor. The patient was successfully treated and had a good clinical outcome.

Aged↗
PubMed2000

Concise enantiospecific synthesis of a coccinellied alkaloid, (-)-adalinine.

[reaction: see text] An enantiospecific synthesis of a coccinellied alkaloid, (-)-adalinine, was established starting from (S)-(-)-pyroglutamic acid, where a stereoselective Michael addition and a samarium iodide-promoted regioselective carbon-nitrogen bond cleavage reaction were involved as the key reactions.

Animals↗
PubMed2000

Complete nucleotide sequence of the prophage VT1-Sakai carrying the Shiga toxin 1 genes of the enterohemorrhagic Escherichia coli O157:H7 strain derived from the Sakai outbreak.

Shiga toxins 1 and 2 (Stx1 and Stx2) are encoded by prophages lysogenized in enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains. Lytic growth of the phage particles carrying the stx1 genes (stx1A and stx1B) of the EHEC O157:H7 strain RIMD 0509952, which was derived from the Sakai outbreak in 1996 in Japan, was induced after treatment with mitomycin C, but the plaque formation of the phage was not detected. We have determined the complete nucleotide sequence of the prophage VT1-Sakai. The integration site of the prophage was identified within the yehV gene at 47.7 min on the chromosome. The stx1 genes were downstream of the Q gene in the prophage genome, suggesting that their expression was regulated by the Q protein, the regulator of the late gene expression of the phage, which is similar to that of the stx1 or stx2 genes carried by the lambdoid phages reported previously. The sequences of the N gene and its recognition sites, nutL and nutR, were not homologous to those of the phages carrying the stx genes thus far reported, but they were very similar to those of bacteriophage phi21. The sequences of the repressor proteins, CI and Cro, that regulate expression of the early genes had low similarities with those of the known repressors of other phages, and their operator sequences were different from any sequence reported. These data suggest that multiple genetic recombination among bacteriophages with different immunities took place to generate the prophage VT1-Sakai. Comparison between the sequences of VT1-Sakai and lambda suggests that the ancestor of VT1-Sakai was produced by illegitimate excision, like lambda gal and bio phages.

Amino Acid Sequence↗
PubMed2000

US3 protein kinase of herpes simplex virus protects primary afferent neurons from virus-induced apoptosis in ICR mice.

Possible roles of the US3 gene of the herpes simplex virus (HSV) in the interaction between the virus and primary afferent neurons were examined. Neuronal apoptosis was observed in the trigeminal ganglion of mice that were infected with the wild-type (wt) of HSV-2 strain 186 and with US3-deficient mutant virus (L1BR1). In wt virus-infected mice, many HSV-immunoreactive (HSV-ir) cells were seen throughout the trigeminal ganglion, although no apoptotic change was detected. On the other hand, HSV-ir cells in L1BR1-infected mice were found only in the ophthalmic division of the trigeminal ganglions. Examination by HSV-immunohistochemistry combined with the terminal deoxynucleotidal transferase (Tdt)-mediated deoxyuridin 5'-triphosphate (dUTP) nick-end labeling (TUNEL) method showed that DNA fragmentation had occurred in almost all HSV-ir cells in the L1BRI-infected ganglion. Ultrastructurally, many viral particles were detected in apoptotic ganglionic neurons of mice infected with L1BR1. These results indicate that US3 protein kinase (US3pk) played a role in protecting HSV-infected primary afferent neurons from apoptotic cell death. The present study suggests that US3pk plays a role when HSV establishes latent infections in the sensory ganglia.

Animals↗
PubMed2000

Disappearance of aortic intramural hematoma and its significance to the prognosis.

BACKGROUND: An aortic intramural hematoma (IMH) is a form of aortic dissection (AD). IMHs regress with time or completely disappear in some patients, whereas they progress to overt AD in other patients. The purpose of the present study was to investigate how IMHs change serially during a follow-up period. METHODS AND RESULTS: We analyzed 44 consecutive medically treated patients with IMHs, in whom transesophageal echocardiography (TEE) was performed serially at both 1 and 6 months after the onset. After TEE, the patients were followed with interviews (mean follow-up 1552+/-539 days). IMHs disappeared at 6 months in 21 patients (48%) (disappearance group), whereas IMHs were still demonstrated at 6 months in 20 patients (45%) (persistent group); in the disappearance group, IMHs disappeared at 1 month in 8 patients (18%). In 3 patients (7%) in whom an IMH was demonstrated at 1 month, overt AD occurred until 6 months. The disappearance group was younger than the persistent group (64+/-11 versus 72+/-8 years, P:<0.01), and the maximum diameter of the aorta was smaller in the disappearance group than in the persistent group (33+/-5 versus 42+/-7 mm, P:<0.01). During the long-term follow-up, overt AD occurred at 7 and 11 months in 2 patients, and progressive aortic dilatation that required surgical treatment occurred at 12 and 24 months in 2 of the persistent group patients, whereas neither overt AD nor progressive aortic dilatation occurred in the disappearance group. In the patients in whom overt AD occurred, the maximal aortic diameter was >45 mm and an IMH was demonstrated at 1 month. On the other hand, those with a maximal aortic diameter of <45 mm or a disappeared IMH did not have overt AD. CONCLUSIONS: IMHs disappeared until 1 month in 18% and until 6 months in 48% of patients with IMHs. The disappearance of IMHs was related to the maximum diameter of the aorta and age. Both a disappeared IMH and a maximal aortic diameter of <45 mm suggest a good prognosis.

Age Factors↗
PubMed2000

Synthetic oleanane and ursane triterpenoids with modified rings A and C: a series of highly active inhibitors of nitric oxide production in mouse macrophages.

We have designed and synthesized 16 new olean- and urs-1-en-3-one triterpenoids with various modified rings C as potential antiinflammatory and cancer chemopreventive agents and evaluated their inhibitory activities against production of nitric oxide induced by interferon-gamma in mouse macrophages. This investigation revealed that 9(11)-en-12-one and 12-en-11-one functionalities in ring C increase the potency by about 2-10 times compared with the original 12-ene. Subsequently, we have designed and synthesized novel olean- and urs-1-en-3-one derivatives with nitrile and carboxyl groups at C-2 in ring A and with 9(11)-en-12-one and 12-en-11-one functionalities in ring C. Among them, we have found that methyl 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oate (25), 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) (26), and methyl 2-carboxy-3,12-dioxooleana-1,9(11)-dien-28-oate (29) have extremely high potency (IC(50) = 0.1 nM level). Their potency is similar to that of dexamethasone although they do not act through the glucocorticoid receptor. Overall, the combination of modified rings A and C increases the potency by about 10 000 times compared with the lead compound, 3-oxooleana-1,12-dien-28-oic acid (8) (IC(50) = 1 microM level). The selected oleanane triterpenoid, CDDO (26), was found to be a potent, multifunctional agent in various in vitro assays and to show antiinflammatory activity against thioglycollate-interferon-gamma-induced mouse peritonitis.

Animals↗
PubMed2000

Rhodium-catalyzed reformatsky-type reaction

A novel Reformatsky-type reaction was developed using RhCl(PPh(3))(3) and diethylzinc. Inter- and intramolecular Reformatsky-type reactions were achieved efficiently under mild reaction conditions to give beta-hydroxy esters.

Journal Article↗
PubMed2000

A fluorescence polarization assay using oligonucleotide probes for the rapid detection of verotoxin-producing Escherichia coli.

A hybridization assay using fluorescence polarization was combined with the asymmetric polymerase chain reaction (PCR) in a method for the detection of the verotoxin type 2 gene of verotoxin-producing Escherichia coli. Six oligonucleotide probes labeled with FITC were designed and evaluated. One of these gave a detection limit of 10(3) colony forming units per assay, and assay results could be obtained within 5 min after PCR. It appears that the detection limit was restricted mainly by the extent and fidelity of PCR amplification, rather than by the sensitivity of the fluorescence polarization technique, indicating that good probe design facilitates the rapid detection of the PCR product. The fluorescence polarization assay, in conjunction with DNA amplification by PCR, is a powerful and widely applicable method for the rapid and sensitive detection of oligonucleotide sequences.

Bacterial Toxins↗
PubMed2000

The nonconserved hydrophilic loop domain of presenilin (PS) is not required for PS endoproteolysis or enhanced abeta 42 production mediated by familial early onset Alzheimer's disease-linked PS variants.

Presenilin 1 (PS1) and presenilin 2 (PS2) are polytopic membrane proteins that are mutated in the majority of early onset familial Alzheimer's disease (FAD) cases. Two lines of evidence establish a critical role for PS in the production of beta-amyloid peptides (Abeta). FAD-linked PS mutations elevate the levels of highly amyloidogenic Abeta ending at residue 42 (Abeta42), and cells with ablated PS1 alleles secrete low levels of Abeta. Several recent reports have shown that the hydrophilic loop (HL) domain, located between transmembrane domains 6 and 7, contains sites for phosphorylation, caspase cleavage, and sequences that bind several PS-interacting proteins. In the present report, we examined the metabolism of PS polypeptides lacking the HL domain and the influence of these molecules on Abeta production. We report that the deletion of the HL domain does not have a deleterious effect on the regulated endoproteolysis of PS, saturable accumulation of PS fragments, or the self-association of PS fragments. Abeta production was not significantly altered in cells expressing HL-deleted PS polypeptides compared with cells expressing full-length PS. Importantly, deletion of the HL domain did not affect FAD mutation-mediated elevation in the production of Abeta42. Furthermore, the deletion of the HL domain did not impair the role of PS1 or PS2 in facilitating Notch processing. Thus, our results argue against a biologically or pathologically relevant role for the HL domain phosphorylation and caspase cleavage and the association of PS HL domain-interacting proteins, in amyloid precursor protein metabolism and Abeta production or Notch cleavage.

Age of Onset↗
PubMed2000

Novel synthetic oleanane and ursane triterpenoids with various enone functionalities in ring A as inhibitors of nitric oxide production in mouse macrophages.

We initially randomly synthesized about 60 oleanane and ursane triterpenoids as potential anti-inflammatory and cancer chemopreventive agents. Preliminary screening of these derivatives for inhibition of production of nitric oxide induced by interferon-gamma in mouse macrophages revealed that 3-oxooleana-1, 12-dien-28-oic acid (B-15) showed significant activity (IC(50) = 5.6 microM). On the basis of the structure of B-15, 19 novel olean- and urs-12-ene triterpenoids with a 1-en-3-one functionality having a substituent at C-2 in ring A have been designed and synthesized. Among them, 3-oxooleana-1,12-diene derivatives with carboxyl, methoxycarbonyl, and nitrile groups at C-2 showed higher activity than the lead compound B-15. In particular, 2-carboxy-3-oxooleana-1, 12-dien-28-oic acid (3) had the highest activity (IC(50) = 0.07 microM) in this group of triterpenoids. The potency of 3 was similar to that of hydrocortisone (IC(50) = 0.01 microM), although 3 does not act through the glucocorticoid receptor. Interesting structure-activity relationships of these novel synthetic triterpenoids are also discussed.

Animals↗
PubMed2000

The coxsackievirus-adenovirus receptor protein as a cell adhesion molecule in the developing mouse brain.

In an attempt to elucidate the molecular mechanisms underlying neuro-network formation in the developing brain, we analyzed 130 proteolytic cleavage peptides of membrane proteins purified from newborn mouse brains. We describe here the characterization of a membrane protein with an apparent molecular mass of 46 kDa, a member of the immunoglobulin superfamily of which the cDNA sequence was recently reported, encoding the mouse homologue of the human coxsackievirus and adenovirus receptor (mCAR). Western and Northern blot analyses demonstrated the abundant expression of mCAR in the mouse brain, the highest level being observed in the newborn mouse brain, and its expression was detected in embryos as early as at 10. 5 days post-coitus (dpc), but decreased rapidly after birth. On in situ hybridization, mCAR mRNA expression was observed throughout the newborn mouse brain. In primary neurons from the hippocampi of mouse embryos the expression of mCAR was observed throughout the cells including those in growth cones on immunohistochemistry. In order to determine whether or not mCAR is involved in cell adhesion, aggregation assays were carried out. C6 cells transfected with mCAR cDNA aggregated homophilically, which was inhibited by specific antibodies against the extracellular domain of mCAR. In addition to its action as a virus receptor, mCAR may function naturally as an adhesion molecule involved in neuro-network formation in the developing nervous system.

Amino Acid Sequence↗