Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus.
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Enzyme Inhibitors↗
Biomedical subjects
Y Hayakawa
Publications and source records attributed to Y Hayakawa.
An unusual isopentenyl diphosphate isomerase found in the mevalonate pathway gene cluster from Streptomyces sp. strain CL190.
A gene cluster encoding five enzymes of the mevalonate pathway had been cloned from Streptomyces sp. strain CL190. This gene cluster contained an additional ORF, orfD, encoding an unknown protein that was detected in some archaebacteria and some Gram-positive bacteria including Staphylococcus aureus. The recombinant product of orfD was purified as a soluble protein and characterized. The molecular mass of the enzyme was estimated to be 37 kDa by SDS-polyacrylamide gel electrophoresis and 155 kDa by gel filtration chromatography, suggesting that the enzyme is most likely to be a tetramer. The purified enzyme contained flavin mononucleotide (FMN) with the amount per tetramer being 1.4 to 1.6 mol/mol. The enzyme catalyzed the isomerization of isopentenyl diphosphate (IPP) to produce dimethylallyl diphosphate (DMAPP) in the presence of both FMN and NADPH. The Escherichia coli plasmid expressing orfD could complement the disrupted IPP isomerase gene in E. coli. These results indicate that orfD encodes an unusual IPP isomerase showing no sequence similarity to those of IPP isomerases identified to date. Based on the difference in enzymatic properties, we classify the IPP isomerases into two types: Type 2 for FMN- and NAD(P)H-dependent enzymes, and type 1 for the others. In view of the critical role of this isomerase in S. aureus and of the different enzymatic properties of mammalian (type 1) and S. aureus (type 2) isomerases, this unusual enzyme is considered to be a suitable molecular target for the screening of antibacterial drugs specific to S. aureus.
Amino Acid Sequence↗
Genetic analysis of exfoliative toxin A-producing Staphylococcus aureus isolated from mastitic cow's milk.
Exfoliative toxin A (ETA), produced by Staphylococcus aureus, is the causative agent of staphylococcal scalded-skin syndrome (SSSS) in children. Recently, we reported that ETA was detected by reverse passive latex agglutination in three isolates of S. aureus from cow's milk, but that these ETA-positive isolates did not cause the so-called Nikolsky sign in neonatal mice. In this study, therefore, the eta gene encoding ETA and regulatory genes of these bovine isolates were analyzed by the polymerase chain reaction (PCR) and sequencing. The eta gene was amplified from three bovine isolates by PCR and their resulting nucleotide sequences found to correspond to the eta gene from the human isolate, except for three nucleotides in the upstream region of the eta open reading frame (ORF). An accessory gene regulator (agr), which is a global regulatory locus, was detected in these bovine isolates by PCR amplification. In addition, the ORF (J-4), located 120 bp upstream from the eta ORF of the human isolate, was also amplified from these bovine isolates, with their nucleotide sequences differing at 32 positions from the human isolate. Bovine and human ORF J-4 equally enhanced production of ETA in the recombinants of the eta gene, suggesting that the variation in bovine ORF J-4 may be not be the cause of the difference in amount of ETA produced by bovine and human isolates.
Animals↗
Facultatively internal fertilization and anomalous embryonic development of a non-copulatory sculpin Hemilepidotus gilberti Jordan and Starks (Scorpaeniformes: Cottidae).
Fertilized residual eggs were observed in the ovaries of spent females of a non-copulatory sculpin Hemilepidotus gilberti Jordan and Starks. Fertilized eggs were present in 23 of 35 females, and approximately 38% of the total residual eggs (n=227) were fertilized. These eggs were thought to be fertilized facultatively with spermatozoa that entered the ovary through ovarian fluid during spawning. The high calcium concentration (1.42+/-0.21 mM kg(-1)) in ovarian fluid, which is beyond the threshold concentration required for fertilization, may allow internal fertilization to occur. Embryos at various developmental stages were observed, but all were deformed and surrounded by unhardened chorions. Since no larvae were observed, all the fertilized residual eggs would have degenerated in the ovary in accordance with other unfertilized residual eggs. These observations suggest that the ovary of the oviparous fish H. gilberti is an unsuitable environment for embryos to develop, possibly because it may be unable to supply developing embryos with needed elements, such as oxygen.
Journal Article↗
Characterization of ultrastructure and its relation with DNA fragmentation in Fas-induced apoptosis of cultured cardiac myocytes.
The purposes of the present study were to define precisely the ultrastructural features of apoptosis in cultured cardiomyocytes and to determine whether DNA fragmentation is essential for the apoptotic morphology. When cultured neonatal murine cardiomyocytes were incubated with an agonistic anti-Fas antibody in the presence of a non-toxic amount of actinomycin D or cycloheximide, approximately 70% of them had lost their viability after 24 h. The dead cardiomyocytes showed the typical ultrastructural changes of apoptosis on transmission and scanning electron microscopy, as well as by positive in situ nick end-labelling (TUNEL), positive Taq polymerase-based in situ ligation, a DNA ladder pattern on gel electrophoresis, and an increase in the active fragment of caspase-3. According to TUNEL at the electron microscopic level, apoptotic nuclear change, cytoplasmic shrinkage, and DNA fragmentation always occurred simultaneously in apoptotic cardiomyocytes. Other ultrastructural features of apoptosis were the appearance of abundant lipid-like structures in the cytoplasm of cardiomyocytes at the early phase, and a high incidence of plasma membrane rupture and formation of apoptotic bodies at the later phase. When zinc, an inhibitor of Ca2+/Mg2+-dependent endonuclease, was added to the present model, activation of caspase-3 and an apoptotic ultrastructure were still observed in spite of the lack of DNA fragmentation, indicating that this type of myocyte death is also apoptosis. In conclusion, the typical apoptotic ultrastructure and DNA fragmentation occur simultaneously in association with caspase-3 activation in Fas-stimulated cultured cardiomyocytes. Apoptotic morphology can, however, be observed even without DNA fragmentation.
Animals↗
The influence of misnaming on object recognition: a case of multimodal agnosia.
We present a case of multimodal agnosia in the visual and tactile modality due to an infarction in the territory of the left posterior cerebral artery. The patient's ability to recognize objects fluctuated depending on his verbal activity. When he misnamed presented objects, he tended to use them and to draw them in keeping with the wrong name. We submit that the mechanism causing associative agnosia is more dynamic than it was hitherto considered. It originates from the rivalry between top-down central regulation and bottom-up peripheral flow.
Aged↗
Nucleotide synthesis via methods without nucleoside-base protection.
Oligonucleotide synthesis via methods without nucleobase protection (N-unprotected methods) is briefly reviewed. The N-unprotected methods are advantageous in the following respects over conventional approaches that use protectors, generally, acyl protectors for the nucleobase (N-protected method). Two steps, introduction and removal of the protecting groups, are eliminated, and consequently use of undesirable reagents involved in these steps are avoided. In the synthesis of DNA oligomers, the risk of depurination of deoxyadenosine and deoxyguanosine derivatives, which is a serious problem in the N-protected methods, is considerably reduced. The range of synthesizable artificial analogues bearing base-labile functions is extended because harsh base treatment for the deprotection is eliminated.
Nucleosides↗
Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells in vitro, but its physiological role in tumor surveillance remains unknown. Here, we report that TRAIL is constitutively expressed on murine natural killer (NK) cells in the liver and plays a substantial role in suppressing tumor metastasis. Freshly isolated NK cells, but not natural killer T cells or ordinary T cells, from the liver expressed cell surface TRAIL, which was responsible for spontaneous cytotoxicity against TRAIL-sensitive tumor cells in vitro along with perforin and Fas ligand (FasL). Administration of neutralizing monoclonal antibody against TRAIL significantly increased experimental liver metastases of several TRAIL-sensitive tumor cell lines. Such an anti-metastatic effect of TRAIL was not observed in NK cell-depleted mice or interferon-gamma-deficient mice, the latter of which lacked TRAIL on liver NK cells. These findings provide the first evidence for the physiological function of TRAIL as a tumor suppressor.
Animals↗
Paediatric absorbed doses from rotational panoramic radiography.
OBJECTIVES: To determine the paediatric doses in rotational panoramic radiography with film/screen and photostimulable phosphor receptors. STUDY DESIGN: A paediatric anthropomorphic head and neck phantom was used. Absorbed doses were measured for two panoramic systems, the Orthophos (Sirona Dental Systems, Bensheim, Germany) and the PM 2002 CC (Planmeca Oy, Helsinki, Finland), with and without programmable child settings, using both screen/film and photostimulable phosphor receptors. RESULTS: Absorbed doses to the eye ranged from 5 to 24 micro Gy. Doses to the dental arches with the Orthophos unit ranged from 50 to 555 micro Gy with the adult and from 27 to 436 micro Gy with the child program; using the PM 2002 CC unit, doses ranged from 56 to 1040 micro Gy using the adult settings, and from 60 to 890 micro Gy with the paediatric settings. The paediatric exposure settings reduced doses at most locations for both panoramic systems. The highest doses were measured near the rotational axes of the X-ray beam. Paediatric settings with the Orthophos P10 resulted in the dose reduction more than 50% to the thyroid but not with the PM 2002 CC. When lower kVcp or mA settings were used, absorbed doses were effectively reduced for all combinations of machines, programs and detectors. CONCLUSIONS: Specific program settings for children reduced the absorbed doses from panoramic radiography irrespective of the machine or receptor used.
Absorption↗
Dopamine is a key factor for the induction of egg diapause of the silkworm, Bombyx mori.
The silkworm, Bombyx mori, enters diapause in the early embryonic stage. Embryonic diapause is induced by incubating eggs of the maternal generation at high temperature (diapause type), whereas incubation at low temperature results in non-diapausing progeny (non-diapause type). Measurement of catecholamine concentrations in haemolymph and brain-subesophageal ganglia (Br-SGs) showed that only dopamine concentrations in both tissues are consistently higher in diapause-type than non-diapause-type larvae and pupae. In particular, the difference in dopamine concentrations in both tissues increases around pupal ecdysis. During the early pupal stage, Dopa decarboxylase activities and mRNA concentrations in Br-SGs were also much higher in diapause-type than non-diapause-type insects. Elevation of dopamine levels induced by feeding Dopa to penultimate-instar and last-instar larvae, and by injecting Dopa or dopamine into pupae 2 days after pupation made the non-diapause-destined insects lay diapause-destined eggs at 59% and approximately 70% frequencies, respectively. Furthermore, injection of Dopa or dopamine elevated mRNA levels of the diapause hormone in the Br-SGs of non-diapause-type pupae 1 day after injection. Incubation of Br-SGs isolated from non-diapause-type day-2 pupae with Dopa or dopamine also stimulated the expression of diapause hormone mRNA. These data indicate that environmental stimuli during embryonic development increase dopamine levels in both hemolymph and Br-SGs from the larval stage to early pupal stage, which results in laying of diapause-destined eggs by female adults through enhanced expression of the diapause hormone gene.
Age Factors↗
A facile synthesis of 5'-end solid-anchored, 3'-end free oligodeoxyribonucleotides via the (5'-->3')-elongated phosphoramidite strategy.
It is demonstrated that not only N2- but also O6-protection of the guanine base is necessary for obtaining the oligodeoxyribonucleotides in high yields and at a high purity in the solid-phase synthesis via the (5'--> 3')-chain elongated phosphoramidite approach.
Molecular Structure↗
Efficient liquid-phase synthesis of short-length nucleotides via the phosphoramidite method using stoichiometric amounts of reactants.
The condensation of a nucleoside phosphoramidite and a nucleoside by the aid of a suitable promoter in stoichiometric use is achieved in acetonitrile in the presence of molecular sieves 3A or 4A to give a desired coupling product in an excellent yield. This strategy is particularly useful for the large-scale synthesis of short nucleotides.
Chemistry, Organic↗
Evaluation of flow properties of dry powder inhalation of salbutamol sulfate with lactose carrier.
The effects of the flow and packing properties of a drug/carrier powder mixture on emission of drug adhering to the carrier from capsules and inhalation devices were investigated. Model powder mixtures were designed consisting of lactose carriers with different particle shapes were prepared by surface treatment and micronized salbutamol sulfate. These powder mixtures were aerosolized by a Spinhaler, and in vitro deposition properties of salbutamol sulfate were evaluated by a twin impinger. The flow properties of the mixed powders were evaluated by the Carr's flowability index (FI) and Hausner's ratio (HR). The packing properties of the mixed powders were determined employing the tapping method. Compared with the powder mixed with the untreated lactose carrier, the FI, HR, and the constant K in Kawakita's equation of the powder mixture prepared using the surface-treated lactose carrier were significantly different, showing that the flow and packing properties of the drug/carrier powder mixture were improved. Using this surface-treated system, the handling of the powder mixture when packing into capsules is improved, which is desirable for handling dry powder inhalants. The fraction (%) of drug emitted from capsules and devices (EM) and the FI of the powder mixture were correlated. As the flow properties improved, the outflow of the powder mixture from capsules and devices became easier, and emission of drug adhering on the carrier from capsules and devices improved. Improvement of the inhalation process, such as the drug particles emitted from the inhalation system, is valuable for increasing inhalation properties of dry powder inhalation.
Aerosols↗
No association found between the Ala54Thr polymorphism of FABP2 gene and obesity and obesity with dyslipidemia in Japanese schoolchildren.
To investigate whether the Ala54Thr polymorphism of the fatty acid binding protein 2 gene is associated with obesity and obesity with dyslipidemia in Japanese schoolchildren, we analyzed 370 children with morbid obesity and 463 control children of normal weight. The allele frequencies did not differ significantly between the control group and the morbidly obese group. The odds ratio (95% confidence interval CI) in obesity of the The54 allele was 1.0 (0.9-1.3). There were no significant differences in obesity index and metabolic characteristics between the two groups. The odds ratio (95% CI) in dyslipidemia of the Thr54 allele was 1.1 (0.8-1.4) in the morbidly obese group. Our data suggested that Ala54Thr polymorphism of the FABP2 gene is not a major contributing factor for obesity and obesity with dyslipidemia in Japanese children.
Adolescent↗
Neuroprotectins A and B, bicyclohexapeptides protecting chick telencephalic neuronal cells from excitotoxicity. I. Fermentation, isolation, physico-chemical properties and biological activity.
Glutamate, an excitatory amino acid, is known to induce neurotoxicity in central nervous system under abnormal conditions such as ischemia, hypoglycemia, epilepsy, Huntington's chorea, Parkinson's disease and Alzheimer's disease. In our search for neuroprotective agents of microbial origin against excitatory neurotoxins, we have isolated two new bicyclohexapeptides, neuroprotectins A and B, together with a known compound complestatin, from the fermentation broth of Streptomyces sp. Q27107. Neuroprotectins protected primary cultured chick telencephalic neurons from glutamate- and kainate-induced excitotoxicities in a dose-dependant fashion.
Animals↗
Neuroprotectins A and B, bicyclohexapeptides protecting chick telencephalic neurons from excitotoxicity. II. Structure determination.
In the course of our search for neuroprotective agents of microbial origin against kainate-induced neurotoxicity, we have succeeded in the isolation of two new bicyclohexapeptides, neuroprotectins A and B, together with a known compound, complestatin, from the fermentation broth of Streptomyces sp. Q27107. They are closely related in structure to complestatin and possess an oxindolylalanine moiety in place of the tryptophan residue present in complestatin.
Molecular Structure↗
Phoenistatin, a new gene expression-enhancing substance produced by Acremonium fusigerum.
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Acremonium↗
Selective cytotoxicity and stereochemistry of aspochalasin D.
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Cell Line↗