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S Okabe

Publications and source records attributed to S Okabe.

At least 19 recordsLinked to original sources

Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia.

The telomerase complex is responsible for telomere maintenance and represents a promising neoplasia therapeutic target. Recently, we have demonstrated that treatment with a G-quadruplex-interactive agent, telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines. In the present study, we investigated the mechanisms of apoptosis induced by telomerase inhibition in acute leukemia. We have found the activation of caspase-3 and poly-(ADP-ribose) polymerase in telomestatin-treated U937 cells (PD20) and dominant-negative DN-hTERT-expressing U937 cells (PD25). Activation of p38 mitogen-activated protein (MAP) kinase and MKK3/6 was also found in telomestatin-treated U937 cells (PD20) and dominant-negative DN-hTERT-expressing U937 cells (PD25); however, activation of JNK and ASK1 was not detected in these cells. To examine the effect of p38 MAP kinase inhibition on growth properties and apoptosis in telomerase-inhibited cells, we cultured DN-hTERT-expressing U937 cells with or without SB203580. Dominant-negative-hTERT-expressing U937 cells stopped proliferation on PD25; however, a significant increase in growth rate was observed in the presence of SB203580. Treatment of SB203580 also reduced the induction of apoptosis in DN-hTERT-expressing U937 cells (PD25). These results suggest that p38 MAP kinase has a critical role for the induction of apoptosis in telomerase-inhibited leukemia cells. Further, we evaluated the effect of telomestatin on the growth of U937 cells in xenograft mouse model. Systemic intraperitoneal administration of telomestatin in U937 xenografts decreased tumor telomerase levels and reduced tumor volumes. Tumor tissue from telomestatin-treated animals exhibited marked apoptosis. None of the mice treated with telomestatin displayed any signs of toxicity. Taken together, these results lay the foundations for a program of drug development to achieve the dual aims of efficacy and selectivity in vivo.

Acute Disease↗

Dynamic magnetic resonance sialography as a new diagnostic technique for patients with Sjögren's syndrome.

OBJECTIVE: To evaluate the clinical utility of dynamic magnetic resonance (MR) sialographic images as a diagnostic tool for patients with Sjögren's syndrome. METHODS: The morphological findings and various kinds of functional parameters in volunteers on dynamic MR sialographic images were compared with those in five patients with definite Sjögren's syndrome. RESULTS: On the MR sialographs of all five patients with Sjögren's syndrome, the so-called 'apple-tree appearance' was seen. The difference in two functional parameters using the dynamic MR sialographic data was elucidated between the two groups. The maximum area of the detectable ducts in the group of patients was significantly smaller (P < 0.001) than that in the group of volunteers. The ratio of change in the detectable ducts in the group of patients was significantly lower (P = 0.011) than that in the group of volunteers. CONCLUSIONS: Our study suggests that dynamic MR sialographic data in addition to MR sialographic images might be useful for the diagnosis of Sjögren's syndrome.

Adult↗

Clinical significance and variation of the advanced calcified stylohyoid complex detected by panoramic radiographs among 80-year-old subjects.

OBJECTIVES: To evaluate the clinical significance and variation of a calcified stylohyoid complex associated with advanced calcification as detected on panoramic radiographs among 80-year-old subjects. METHODS: Panoramic radiographs of 659 patients (262 men and 397 women) and data of their general and dental health conditions were used for the evaluation of the relationship between a calcified stylohyoid complex and general health among 80-year-olds. This study was part of the 8020 Data Bank Survey, which was designed to collect the baseline data of general and dental health conditions in 80-year-old subjects. The morphology of the calcified stylohyoid complexes was allocated to one of 12 patterns. The lengths of the calcified stylohyoid complex were measured directly on the radiographs from the caudal margin of the tympanic plate to the tip of the styloid process. RESULTS: All of the stylohyoid complexes from the 659 panoramic radiographs could be allocated to one of 12 morphological patterns, and some of their radiographic findings suggested calcification of the carotid artery and lymph nodes. In 80-year-old subjects, the average length of the calcified stylohyoid complexes was 36.7 mm, and ranged from 0.0 mm to 153.0 mm. There appeared to be correlations between the length of the calcified stylohyoid complex and serum calcium concentration and heel bone density, but not with the Community Periodontal Index (CPI). CONCLUSIONS: Dentists should recognize the existence of morphological variation in calcified stylohyoid complexes, especially in length, apparent on panoramic radiographs of 80-year-old patients. In addition, the longer length of the calcified stylohyoid complexes in 80-year-old patients may be a predictor of bone density and high serum calcium concentration level. The findings from the present study may provide potentially life-saving information about elderly people.

Aged, 80 and over↗

Correlation between the incidence of central nodal necrosis in cervical lymph node metastasis and the extent of differentiation in oral squamous cell carcinoma.

OBJECTIVES: To investigate the incidence of central nodal necrosis (CNN) in the cervical lymph nodes of patients with oral squamous cell carcinoma (SCC) and the factors that influence the formation of CNN. METHODS: Lymph nodes shown as CNN on computed tomography (CT) films in 107 lymph nodes from 27 patients with oral SCC were selected. Lymph nodes with CNN on CT films were compared with the pathological findings of lymph nodes on specimens. We compared many kinds of factors influencing the formation of CNN, including the differentiated type, with the incidence of CNN. RESULTS: Significant relationships were found between the incidence of CNN in metastatic lymph nodes and the presence of well-differentiated SCC and the presence of keratinization in tumour cells. CONCLUSIONS: The results indicated that if a patient had SCC with low-grade differentiation, CNN in small lymph nodes would be difficult to detect on CT scan. Therefore, noting changes in lymph node density in the absence of CNN on CT scans is necessary in case the primary tumour is low-grade SCC.

Adult↗

Equilateral-triangular shape in 14C.

An equilateral-triangular shape of three alpha clusters surrounded by excess neutrons is suggested for 14C, based on the molecular-orbit model. It is found that the attractive interaction between an excess neutron and an alpha particle stabilizes the K(pi)=0(+) and 3(-) rotational bands, which demonstrates an equilateral-triangular symmetry. This K(pi)=3(-) band at 3 MeV below the 10Be+alpha threshold energy corresponds to the experimentally observed band built on top of the second 3(-) state. A positive-parity rotational band (0(+), 2(+), 4(+)) arises similarly. These two bands suggest a molecular 3-alpha structure stabilized by the excess neutrons and can be viewed as a realization of the alpha crystallization in the dilute nuclear medium.

Journal Article↗

Radiographic examination of the mandibular (glenoid) fossa in ancient and modern man.

OBJECTIVE: To compare the morphology of the mandibular (glenoid) fossa between ancient and modern Japanese. METHODS: There were 221 specimens from the ancient period and 206 specimens from the modern period. Radiographs of the mandibular fossa were obtained using a modified Schuller technique and were studied. The length, depth, and area of the mandibular fossa and angulation of the frontal slope of the mandibular fossa on the radiographs were automatically computed. In addition, morphological changes of the mandibular fossa in the ancient or modern periods on radiographs were evaluated in order to assess tendency of temporomandibular joint disorder (TMD). RESULT: The ratio of mandibular fossa having morphological alternation in the modern period was greater than that in the Yayoi. Differences in the length and area between the right and left sides became progressively larger from the Yayoi to modern periods. The angulation of the anterior slope of the mandibular fossa in the modern period was smaller than that in other periods. CONCLUSION: The morphology of the mandibular fossa was shown to have changed and asymmetry has increased from the Yayoi to modern periods. It can be speculated that this change in morphology of the mandibular fossa in the modern period is the result of an increase of TMD.

Cephalometry↗

Effects of indomethacin and rofecoxib on gastric mucosal damage in normal and Helicobacter pylori-infected mongolian gerbils.

This study examined the effects of indomethacin and rofecoxib on normal and Helicobacter pylori (H. pylori)-infected gastric mucosa of Mongolian (M.) gerbils. M. gerbils (6-wk-old) were orally administered H. pylori (ATCC43504, 2 x 10(8) CFU/ml) after fasting for 24 hours. Beginning 3 mo after inoculation, indomethacin (2 mg/kg, s.c) or rofecoxib (10 mg/kg, p.o.) was administered once daily for 2 wk to the gerbils. At autopsy, gastric mucosal ulcer area, myeroperoxidase (MPO) activity, prostaglandin (PG) E(2) synthesis, and H. pylori viability were determined. Histamine-stimulated gastric acid secretion was measured with the acute gastric fistula method. Histological study was performed with H&E staining. H. pylori infection caused severe mucosal damage and production of lymphoid follicles in the gastric submucosa. In H. pylori-infected gerbils, indomethacin aggravated the gastric mucosal damage induced by H. pylori infection. Furthermore, indomethacin by itself induced gastric ulcers at an incidence of 6/10. In contrast, rofecoxib did not aggravate the H. pylori-induced mucosal damage. Indomethacin and rofeocoxib significantly reduced H. pylori viability. MPO activity was significantly increased in H. pylori-infected gerbils compared with H. pylori-uninfected gerbils. Indomethacin and rofecoxib reduced MPO activity in H. pylori-infected gerbils. PGE(2) synthesis was markedly increased in H. pylori-infected gerbils (approximately 3-times) compared with the normal gerbils. Indomethacin significantly inhibited PGE(2) synthesis in the gastric mucosa, both in normal and H. pylori-infected gerbils. Rofecoxib did not reduce PGE(2) synthesis in normal gerbils, however, PGE(2) synthesis was reduced to normal levels in H. pylori-infected gerbils. In H. pylori-infected gerbils, histamine-stimulated gastric acid secretion was reduced compared with normal gerbils. Indomethacin significantly increased histamine-stimulated gastric acid secretion and rofecoxib tended to increase secretion in H. pylori-infected gerbils. It was concluded that indomethacin enhances development of gastric mucosal damage in normal gerbils and aggravates H. pylori-induced gastric damage, resulting in gastric ulcers. Rofecoxib did not induce gastric damage in normal gerbils and did not aggravate damage in H. pylori-infected gerbils, suggesting that rofecoxib is less damaging to the stomach than indomethacin.

Administration, Oral↗

Effects of hydroxylamine on microbial community structure and function of autotrophic nitrifying biofilms determined by in situ hybridization and the use of microelectrodes.

Effects of hydroxylamine (NH2OH), an intermediate of NH4+ oxidation, on microbial community structure and function of two autotrophic nitrifying biofilms fed with and without NH2OH were analyzed by a 16S rRNA approach and the use of microelectrodes. In the NH2OH-added biofilm, partial oxidation of NH4+ to NO2- was observed, whereas complete oxidation of NH4+ to NO3- was achieved in the control biofilm. In situ hybridization results revealed that no nitrite-oxidizing bacteria (NOB) hybridized with any specific probes were detected in the NH2OH-added biofilm. Thus, the addition of low concentrations of NH2OH (250 microM) completely inhibited the growth of NOB. Phylogenetic analysis of 16S rDNA indicated that the ammonia-oxidizing bacteria (AOB) detected in both biofilms were closely related to Nitrosomonas europaea, and that the clone sequences from both biofilm libraries have more than 99% similarity to each other. However, in situ hybridization results revealed that the addition of NH2OH changed the form of growth pattern of the dominant Nitrosomonas spp. from dense clusters mode to single scattered cells mode. Microelectrode measurements revealed that the average NH4+ consumption rate calculated in the NH2OH-added biofilm was two times higher than that in the control biofilm. This clearly demonstrated that the oxidation of NH4+ was stimulated by NH2OH addition.

Biofilms↗

Microbial communities and their interactions in biofilm systems: an overview.

Several important advances have been made in the study of biofilm microbial populations relating to their spatial structure (or architecture), their community structure, and their dependence on physicochemical parameters. With the knowledge that hydrodynamic forces influence biofilm architecture came the realization that metabolic processes may be enhanced if certain spatial structures can be forced. An example is the extent of plasmid-mediated horizontal gene transfer in biofilms. Recent in situ work in defined model systems has shown that the biofilm architecture plays a role for genetic transfer by bacterial conjugation in determining how far the donor cells can penetrate the biofilm. Open channels and pores allow for more efficient donor transport and hence more frequent cell collisions leading to rapid spread of the genes by horizontal gene transfer. Such insight into the physical environment of biofilms can be utilized for bioenhancement of catabolic processes by introduction of mobile genetic elements into an existing microbial community. If the donor organisms themselves persist, bioaugmentation can lead to successful establishment of newly introduced species and may be a more successful strategy than biostimulation (the addition of nutrients or specific carbon sources to stimulate the authochthonous population) as shown for an enrichment culture of nitrifying bacteria added to rotating disk biofilm reactors using fluorescent in situ hybridization (FISH) and microelectrode measurements of NH4+, NO2-, NO3-, and O2. However, few studies have been carried out on full-scale systems. Bioaugmentation and bioenhancement are most successful if a constant selective pressure can be maintained favoring the promulgation of the added enrichment culture. Overall, knowledge gain about microbial community interactions in biofilms continues to be driven by the availability of methods for the rapid analysis of microbial communities and their activities. Molecular tools can be grouped into those suitable for ex situ and in situ community analysis. Non-spatial community analysis, in the sense of assessing changes in microbial populations as a function of time or environmental conditions, relies on general fingerprinting methods, like DGGE and T-RFLP, performed on nucleic acids extracted from biofilm. These approaches have been most useful when combined with gene amplification, cloning and sequencing to assemble a phylogenetic inventory of microbial species. It is expected that the use of oligonucleotide microarrays will greatly facilitate the analysis of microbial communities and their activities in biofilms. Structure-activity relationships can be explored using incorporation of 13C-labeled substrates into microbial DNA and RNA to identify metabolically active community members. Finally, based on the DNA sequences in a biofilm, FISH probes can be designed to verify the abundance and spatial location of microbial community members. This in turn allows for in situ structure/function analysis when FISH is combined with microsensors, microautoradiography, and confocal laser scanning microscopy with advanced image analysis.

Bacteria↗

Glycoconjugates with NeuAc-NeuAc-Gal-Glc are more effective at preventing adhesion of Helicobacter pylori to gastric epithelial cells than glycoconjugates with NeuAc-Gal-Glc.

Helicobacter pylori (H. pylori) adheres to human gastric epithelial cells, eliciting various gastroduodenal diseases. Gangliosides play a critical role in bacterial adhesion to cell surfaces. The present study examined how residues of gangliosides are important for inhibition of adhesion of H. pylori to MKN-45 cells. We measured adhesion or detachment effects of gangliosides on the interaction between MKN-45 cells and H. pylori, as well as interleukin-8 production. Among the gangliosides, O-Ac-GD3, GT(1b), GD(1a), GD(1b), GT(1a), and GD3 had potent dose dependent inhibitory effects on adhesion of H. pylori to MKN-45 cells, interleukin-8 production, and vacuole formation induced by H. pylori toxin binding to Vero cells. GD3 also accelerated bacterial detachment of MKN-45 cells with adherent H. pylori in a dose dependent manner. Such results strongly suggest that the mechanism involved in the inhibition of H. pylori adhesion is mediated by the variations of the residues of the NeuAc-NeuAc-Gal-Glc chain of gangliosides. NeuAc-NeuAc-Gal-Glc exhibits a more inhibitory effect on adhesion than the NeuAc-Gal-Glc chain. Such gangioside and oligosaccrharide sequences appear to have therapeutic importance for prevention of H. pylori adhesion, as well as reduction of both inflammation and gastric mucosal injuries.

Animals↗

Sulfate-reducing bacterial community structure and their contribution to carbon mineralization in a wastewater biofilm growing under microaerophilic conditions.

The community structure of sulfate-reducing bacteria (SRB) and the contribution of SRB to carbon mineralization in a wastewater biofilm growing under microaerophilic conditions were investigated by combining molecular techniques, molybdate inhibition batch experiments, and microelectrode measurements. A 16S rDNA clone library of bacteria populations was constructed from the biofilm sample. The 102 clones analyzed were grouped into 53 operational taxonomic units (OTUs), where the clone distribution was as follows: Cytophaga- Flexibacter- Bacteroides (41%), Proteobacteria (41%), low-G+C Gram-positive bacteria (18%), and other phyla (3%). Three additional bacterial clone libraries were also constructed from SRB enrichment cultures with propionate, acetate, and H(2) as electron donors to further investigate the differences in SRB community structure due to amendments of different carbon sources. These libraries revealed that SRB clones were phylogenetically diverse and affiliated with six major SRB genera in the delta-subclass of the Proteobacteria. Fluorescent in situ hybridization (FISH) analysis revealed that Desulfobulbus and Desulfonema were the most abundant SRB species in this biofilm, and this higher abundance (ca. 2-4x10(9) cells cm(-3) and 5x10(7) filaments cm(-3), respectively) was detected in the surface of the biofilm. Microelectrode measurements showed that a high sulfate-reducing activity was localized in a narrow zone located just below the oxic/anoxic interface when the biofilm was cultured in a synthetic medium with acetate as the sole carbon source. In contrast, a broad sulfate-reducing zone was found in the entire anoxic strata when the biofilm was cultured in the supernatant of the primary settling tank effluent. This is probably because organic carbon sources diffused into the biofilm from the bulk water and an unknown amount of volatile fatty acids was produced in the biofilm. A combined approach of molecular techniques and batch experiments with a specific inhibitor (molybdate) clearly demonstrated that Desulfobulbus is a numerically important member of SRB populations and the main contributor to the oxidation of propionate to acetate in this biofilm. However, acetate was preferentially utilized by nitrate-reducing bacteria but not by acetate-utilizing SRB.

Biofilms↗

Effect of dissolved oxygen concentration on the biofilm and in situ analysis by fluorescence in situ hybridization (FISH) and microelectrodes.

A better understanding of microbiology and ecology of nitrifying bacteria in inner biofilms is an important part of improving process performance and control. Microelectrodes and fluorescent in situ hybridization (FISH) in biofilm research have been used to investigate the spatial distributions of various microbial activities in biofilms and have led to new experimental findings as well as modifications of the homogeneous assumptions in the biofilm kinetic models. The objective of this study is to try the combination of two methods, both FISH and microelectrode measurements, and to provide reliable and in situ information on nitrifying bacterial activity in biofilms. The characteristics of biofilm developed on tygon slides were different according to the change of dissolved oxygen (DO). When the DO increased from 2 to 10 mg DO/L, the rate of the biofilm thickness increased and its dry density changed from 50-70 to 25-90 mg/cm3. Ammonia oxidizing bacteria were not uniformly distributed in biofilm, and were found at the deeper layer where oxygen is depleted, they were detected primarily in the upper and middle layers of the biofilm.

Bacteria↗

Effect of nitrite and nitrate on biogenic sulfide production in sewer biofilms determined by the use of microelectrodes.

The effects of O2 and NO3- concentrations on in situ sulfate reduction and sulfide reoxidation in microaerophilic wastewater biofilms grown on rotating disk reactors were investigated by the use of microelectrodes for O2, S2-, NO3-, NO2-, and pH. Microelectrode measurements showed the vertical microzonation of O2 respiration, NO3- respiration, H2S oxidation and SO4(2-) reduction in the biofilms. The microelectrode measurements indicate that sulfate reducing activity was largely restricted to a narrow anaerobic zone located about 500 microm below the biofilm surface. An addition of nitrate forced the sulfate reduction zone deeper in the biofilm and reduced the specific sulfate reduction rate as well. The sulfate reduction zone was consequently separated from the O2 and NO3- respiration zones. Anaerobic H2S oxidation with NO3- was also induced by addition of nitrate to the medium. Measurements of the reduced inorganic sulfur compounds (FeS, FeS2 and S0), total-Mn and total-Fe in the biofilm indicated that the produced H2S became immediately oxidized with O2, NO3- and other oxidants, mainly ferric/ferrous hydrates. On the basis of the present results, it was estimated that of all sulfide produced, 13% of the sulfide was precipitated by metal ions as FeS and S0 just above the sulfate reduction zone, 65% was anaerobically oxidized to SO4(2-) with NO3- as an electron acceptor and 22% was aerobically oxidized within the biofilm incubated in 70 micromol l(-1) of DO and 280 micromol l(-1) of NO3-.

Biofilms↗

Characterization of "unhealed gastric ulcers" produced with chronic exposure of acetic acid ulcers to indomethacin in rats.

We previously discovered that a 4-wk course of indomethacin delivered to rats with acetic acid ulcers resulted in production of "unhealed gastric ulcers" that persisted for up to 12 wks after treatment cessation. The present study examined the mechanism underlying such "unhealed gastric ulcers" with biochemical and histological procedures. "Unhealed gastric ulcers" were induced with a 4-wk indomethacin treatment (1 mg/kg, twice daily) in rats with acetic acid ulcers. Two and 4 wks after treatment cessation, ulcer size was significantly larger in rats receiving indomethacin compared with control animals. Ulcerated tissue prostaglandin E2 levels were significantly lower during indomethacin treatment, but the levels tended to increase after treatment cessation compared with levels measure in the group receiving vehicle. Myeloperoxidase activity levels were significantly higher during indomethacin treatment; such levels persisted after treatment cessation. Histologically, greater degrees of fibrosis and neutrophil accumulation, as well as a lesser degree of angiogenesis were observed in the "unhealed gastric ulcers" compared to ulcers that healed in a normal fashion. It was concluded that severe fibrosis, persistent neutrophil infiltration, and poor angiogenesis in the ulcer base might represent factors involved in the mechanism underlying production of "unhealed gastric ulcers".

Acetic Acid↗

Wine stimulates gastric acid secretion in isolated rabbit gastric glands via two different pathways.

BACKGROUND & AIMS: Alcoholic beverages such as beer and wine are well known to potently stimulate gastric acid secretion, most probably through an increase in circulating gastrin level. The present study examined whether or not wine stimulates gastric acid secretion by a direct effect on parietal cells, enterochromaffin-like (ECL) cells or both. METHODS: Gastric mucosa was isolated from female Japanese white rabbits and gland specimens were prepared by the collagenase digestion method. Acid secretion was assessed by gland accumulation of [14C] aminopyrine. The effects of red wine, ethanol, non-alcoholic wine and drugs were determined by incubating gastric glands with aminopyrine. Radioactivity in solubilized glands was determined by a liquid scintillation counting. RESULTS: Neither wine nor ethanol (diluted 1 : 10(2) to 1 : 10(4)) had any effect on gastric acid secretion, whereas non-alcoholic wine stimulated acid secretion in a dose-dependent manner. All substances, however, significantly stimulated gastric acid secretion in IBMX (phosphodiesterase inhibitor)-pretreated glands. S-0509 (a CCK-2 receptor antagonist) and atropine had no effect on acid secretion stimulated by wine, ethanol or non-alcoholic wine in IBMX-pretreated glands. Famotidine and omeprazole significantly inhibited the acid secretion resulting from all of the above stimulants. BAPTA (an intracellular Ca2+ chelator) inhibited acid secretion stimulated with wine or ethanol in a dose-dependent manner, but did not inhibit secretion stimulated by non-alcoholic wine. CONCLUSIONS: Wine was found to stimulate gastric acid secretion in gastric glands via two pathways, by an ethanol-induced increase in the concentration of intracellular Ca2+ in parietal cells, and by histamine release from ECL cells potentially induced by constituents present in wine.

Animals↗

Discrete roles of cytokines, TNF-alpha, IL-1, IL-6 in tumor promotion and cell transformation.

Based on our previous results, which pointed to tumor necrosis factor-alpha (TNF-alpha) as the essential cytokine in tumor promotion in mouse skin, we present here three principal findings related to the specific roles of TNF-alpha, interleukin-1 (IL-1) and IL-6 in tumor promotion (using TNF-alpha- and IL-6-deficient mice) and in BALB/3T3 cell transformation: i) The previously reported residual tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in TNF-/- mice was confirmed by experiments with TNF+/+ and TNF-/- 129/Svj mice of the same strain, using two-stage carcinogenesis experiments. TPA produced tumors in 100% of TNF+/+ and 78% of TNF-/- mice at 20 weeks, and the average number of tumors per mouse was 11.1 in the former group and 2.1 in the latter. Judging from the expression of various inflammatory cytokine genes in TNF+/+ and TNF-/- mice, the residual tumor promoting activity of TPA in TNF-/- mice may be dependent on expression of IL-1alpha and IL-1beta genes. ii) Tumor promotion by TPA and okadaic acid in IL-6+/+ and IL-6-/- C57/BL6 mice was studied, with TPA producing tumors in 57.1% of IL-6+/+ and 40.0% of IL-6-/- mice at 20 weeks, and okadaic acid in 40.0% of IL-6+/+ and 53.3% of IL-6-/- mice. Thus, there was no significant difference between TPA or okadaic acid tumor promotion in either group. In addition, expression of IL-6 gene in skin of both types of mice suggested that IL-6 is not the essential cytokine in tumor promotion, since it can be replaced by other cytokines. iii) In transformed clones of BALB/3T3 cells induced by TNF-alpha alone, IL-1alpha gene expression was induced after transformation by TNF-alpha had occurred, which did not occur in parental cells. Expression patterns of TNF-alpha, IL-1beta, IL-6 and IL-10, along with TGF-beta, were similar in both parental and transformed cells. Considering all these results, we conclude that various cytokines have discrete roles in tumor promotion and cell transformation.

9,10-Dimethyl-1,2-benzanthracene↗

Structure and function of nitrifying biofilms as determined by molecular techniques and the use of microelectrodes.

The phylogenetic diversity of a nitrifying bacterial community of two types of nitrifying biofilms, a domestic wastewater biofilm and an autotrophic nitrifying biofilm grown on rotating disk reactors (RDR), was characterized by 16S ribosomal DNA (rDNA)-cloning analysis. Thereafter, successional development of nitrifying the bacterial community within both biofilms was visualized in situ by fluorescent in situ hybridization (FISH) wih a set of fluorescently labeled 16S rRNA-targeted DNA probes. In situ hybridization revealed that Nitrosomonas ureae was the numerically dominant species of the ammonia-oxidizing population in the domestic wastewater biofilm and that a population shift from N. urea to N. europaea and N. eutropha occurred when the culture medium was switched to the synthetic media from the domestic wastewater. After reaching the steady-state condition, microprofiles of NH4+, NO2-, NO3-, and O2 in the biofilms were measured by use of microsensors, and the spatial distributions of in situ nitrifying activities were determined. The relationship between the spatial organization of nitrifying bacterial populations and the in situ activity of these populations within the biofilms was discussed. Microelectrode measurements revealed that the active ammonia-oxidizing zone was vertically separated from the active nitrite-oxidizing zone. This vertical separation became more evident with increase of the substrate C/N ratio, leading to deterioration of nitrification efficiency. The combined use of these techniques made it possible to relate in situ nitrifying activity directly to the occurrence of nitrifying bacterial populations.

Ammonia↗

Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels.

PSD-Zip45 (Homer 1c) and PSD-95 are postsynaptic density (PSD) proteins containing distinct protein-interacting motifs. Green fluorescent protein (GFP)-tagged PSD-Zip45 and PSD-95 molecules were targeted to the PSD in hippocampal neurons. We analyzed dynamic behavior of these GFP-tagged PSD proteins by using time-lapse confocal microscopy. In contrast to the less dynamic properties of PSD-95, PSD-Zip45 showed rapid redistribution and a higher steady-state turnover rate. Differential stimulation protocols were found to alter the direction of PSD-Zip45 assembly-disassembly. Transient increases in intracellular Ca(2+) by voltage-dependent Ca(2+) channel activation induced PSD-Zip45 clustering. In contrast, NMDA receptor-dependent Ca(2+) influx resulted in the disassembly of PSD-Zip45 clusters. Thus, neuronal activity differentially redistributes a specific subset of PSD proteins, which are important for localization of both surface receptors and intracellular signaling complexes.

Animals↗