Search PubMed⌕ Search

Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 37 records · Page 2Linked to original sources

A low-cost municipal sewage treatment system with a combination of UASB and the "fourth-generation" downflow hanging sponge reactors.

This paper presents an evaluation of the process performance of a pilot-scale "fourth generation" downflow hanging sponge (DHS) post-treatment system combined with a UASB pretreatment unit treating municipal wastewater. After the successful operation of the second- and third-generation DHS reactors, the fourth-generation DHS reactor was developed to overcome a few shortcomings of its predecessors. This reactor was designed to further enhance the treatment efficiency and simplify the construction process in real scale, especially for the application in developing countries. Configuration of the reactor was modified to enhance the dissolution of air into the wastewater and to avert the possible clogging of the reactor especially during sudden washout from the UASB reactor. The whole system was operated at a total hydraulic retention time (HRT) of 8 h (UASB: 6 h and DHS: 2 h) for a period of over 600 days. The combined system was able to remove 96% of unfiltered BOD with only 9 mg/L remaining in the final effluent. Likewise, F. coli were removed by 3.45 log with the final count of 10(3) to 10(4) MPN/100 ml. Nutrient removal by the system was also satisfactory.

Bacteria, Anaerobic↗

Minimization of greenhouse gas emission by application of anaerobic digestion process with biogas utilization.

To assess the impact on greenhouse gas emission, different process schemes for municipal sludge treatment were evaluated based on the data from pilot-scale experiments and review of annual operation reports. A modified anaerobic digestion process with partial ozonation of digested sludge to improve biological degradability and the conventional anaerobic digestion process were compared with respect to the energy demand in each process schemes. Options for beneficial use of biogas included (1) application of biogas for power production and (2) recovery as an alternative to natural gas utilization. The analysis indicated that the partial ozonation process with power production led to minimal greenhouse gas emission because the extra energy production from this scheme was expected to cover all of the energy demand for the plant operation. Moreover, the final amount of dewatered sludge cake was only 40% of that expected from the conventional process, this significantly minimizes the potential for greenhouse gas emission in the subsequent sludge incineration processes.

Bacteria, Anaerobic↗

Effects of bisphosphonates on joint damage and bone loss in rat adjuvant-induced arthritis.

OBJECTIVE AND DESIGN: Examination of the effects of bisphosphonates on joint damage and generalized bone loss. MATERIALS: Adjuvant-arthritis was induced by injection of Mycobacterium butyricum into the footpad of the right hind paw of Lewis rats (8 animals/group) on day 0. TREATMENT: Arthritic rats were treated with the vehicle (saline), etidronate or alendronate (subcutaneously, daily 5 times a week for 3 weeks from day 1 to day 21). Experiment-1: Etidronate (0.1, 0.5, 2.5, 12.5 mg/kg) or alendronate (0.02, 0.1, 0.5, 2.5 mg/kg), Experiment-2: Etidronate (2.5, 5, 10mg/ kg) or alendronate (0.001, 0.01, 0.1 mg/kg). METHODS: In the adjuvant-injected side of the hind limbs, paw swelling was evaluated at 1-week intervals, and bone mineral density (BMD) in the proximal tibia, histopathology and radiographical findings in the tibio-tarsal region were evaluated at the time of sacrifice (on day 21). RESULTS: In all treatment schedules, both bisphosphonates significantly prevented paw swelling and bone loss. Alendronate reduced paw swelling at higher doses (over 0.1 mg/ kg) compared with its effect on BMD decrease (over 0.001 mg/kg). In contrast, etidronate reduced paw swelling and joint damage at doses similar to those (over 2.5 mg/kg) prevented BMD decrease. CONCLUSIONS: Both etidronate and alendronate are effective in reducing arthritic damage, but their effective dose ranges for inflammatory responses and BMD decrease clearly differ; i.e., the etidronate dose ranges for anti-inflammatory and anti-resorptive effects are similar, whereas the dose range for anti-inflammatory effects of alendronate is 100-fold higher than that for its anti-resorptive effects.

Alendronate↗

Role of basal ganglia-brainstem pathways in the control of motor behaviors.

Here we review a role of a basal ganglia-brainstem (BG-BS) system throughout the mesopontine tegmentum in the control of various types of behavioral expression. First the basal ganglia-brainstem system may contribute to an automatic control of movements, such as rhythmic limb movements and adjustment of postural muscle tone during locomotion, which occurs in conjunction with voluntary control processes. Second, the basal ganglia-brainstem system can be involved in the regulation of awake-sleep states. We further propose the possibility that the basal ganglia-brainstem system is responsible for the integration of volitionally-guided and emotionally-triggered expression of motor behaviors. It can be proposed that dysfunction of the basal ganglia-brainstem system together with that of cortico-basal ganglia loop underlies the pathogenesis of behavioral disturbances expressed in basal ganglia dysfunction.

Basal Ganglia↗

Evidence for a role of basal ganglia in the regulation of rapid eye movement sleep by electrical and chemical stimulation for the pedunculopontine tegmental nucleus and the substantia nigra pars reticulata in decerebrate cats.

The present study was to determine how afferents from the substantia nigra pars reticulata (SNr) of the basal ganglia to the pedunculopontine tegmental nucleus (PPN) in the brainstem could contribute to the control of behavioral states. We used anesthetized and acutely decerebrated cats (n=22). Repetitive electrical stimulation (10-100 Hz, 20-50 microA, for 4-20 s) to the ventrolateral part of the PPN produced rapid eye movement (REM) associated with a suppression of postural muscle tone (REM with atonia). Although repetitive electrical stimuli (10-200 Hz, 10-60 microA, for 5-20 s) delivered to the dorsolateral part of the SNr did not evoke eye movements or muscular tonus in baseline conditions, it altered the PPN-induced REM with atonia. The following three types of effects were induced: (1) attenuation of the REM with atonia; (2) attenuation of muscular atonia without changes in REM (REM without atonia); and (3) attenuation of only REM. The optimal stimulus sites for these effects were intermingled within the lateral part of the SNr. The PPN-induced REM with atonia was abolished by an injection into the PPN of muscimol (1-15 mM, 0.1-0.25 microl), a GABAA receptor agonist, but not altered by an injection of baclofen (1-10 mM, 0.1-0.25 microl), a GABAB receptor agonist. Moreover, an injection of bicuculline (1-15 mM, 0.1-0.25 microl), a GABAA receptor antagonist, into the PPN, resulted in REM with atonia. On the other hand, an injection of muscimol into the dorsolateral part of the SNr (1-15 mM, 0.1-0.25 microl) induced REM with atonia, which was in turn eliminated by a further injection of muscimol into the PPN (5-10 mM, 0.2-0.25 microl). These results suggest that a GABAergic projection from the SNr to the PPN could be involved in the control of REM with atonia, signs which indicate REM sleep. An excessive GABAergic output from the basal ganglia to the PPN in parkinsonian patients may induce sleep disturbances, including a reduction of REM sleep periods and REM sleep behavioral disorders (REM without atonia).

Animals↗

Midkine induced growth of ameloblastoma through MAPK and Akt pathways.

Midkine (MK) is expressed during tooth development and, since ameloblastoma is thought to be arisen from the epithelium of the odontogenic apparatus or its remnant tissues, the effect of MK in ameloblastoma cell growth should be examined. The expression and function of MK were examined using 37 ameloblastoma tissues and AM-1 cells, an HPV-16DNA transfected ameloblastoma cell line. We found that MK was immunohistochemically expressed in 70% of ameloblastoma cases and AM-1 cells. By stimulation with 100 ng/ml MK, the growth of AM-1 cells was accelerated two fold by the 9th day. MK could induce phosphorylation of p44/42 MAPK (Thr202/Tyr204) and Akt (Ser473 and Thr308), and by pretreatment of PD98059, MEK1 inhibitor, or LY294002, PI3K inhibitor, MK-stimulated-phosphorylation of MAPK and Akt and MK-stimulated growth of AM-1 cells were inhibited. These results suggested that MK induced growth of ameloblastoma is through the MAPK and Akt pathways.

Ameloblastoma↗

Sweating responses during activation of the muscle metaboreflex in humans is altered by time of day.

AIM: The aim of the present study was to test for a time-of-day effect on sweating responses to activation of the muscle metaboreflex. METHODS: Eight male subjects each participated in two exercise sessions, one in the morning and one in the evening. Within each session there were two 60-s bouts of isometric handgrip (IHG) exercise at 50% maximal voluntary contraction. Prior to IHG, whole body warming by a water-perfused suit initiated mild sweating. The first bout of IHG exercise began at 06.00 hours (am) and 18.00 hours (pm). Blood circulation to the forearm was occluded for 120 s, beginning 5 s before the end of the second bout of IHG to activate the muscle metaboreflex. RESULTS: During both bouts of exercise, sweating rate (SR) on both the chest and right forearm significantly increased from the pre-exercise period in both am and pm sessions. SR rapidly decreased during first minute of recovery after the first bout of IHG exercise. However, during post-exercise ischaemia (PEI) after the second bout of IHG exercise, SR was maintained significantly above the pre-exercise level only in the pm session. The increases in SR on the chest and right forearm during PEI were significantly greater in the pm, than in the am, session. However, SR of the palm was not maintained during PEI. CONCLUSIONS: We conclude that under mild hyperthermic conditions, the sweating response in non-glabrous skin to activation of the muscle metaboreflex exhibits a time-of-day effect.

Adult↗

A case of plasmacytic hyperplasia arising in a kidney allograft salvaged with immunosuppression reduction alone.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation. Plasmacytic hyperplasia (PH) is thought of as the mildest form of PTLD; however, a graftectomy is necessary in most situations. We experienced an interesting case of PH arising in a kidney allograft, which could be relieved with a reduction in immunosuppression. A 27-year-old female underwent a living-related kidney transplantation. A 3-month non-episode protocol biopsy unexpectedly showed the devastating appearance of polymorphic plasma cell infiltration into the graft intersitium, compatible with PH. The PH was located in the graft by radiographic examinations. The infiltration of plasma cell disappeared completely on the 6-month graft biopsy specimen following immunosuppression reduction and the graft is functioning, although it was damaged by a subsequent acute rejection. Our present case indicates that some PTLD can be completely cured with a reduction in immunosuppression alone. The diagnostic modality for the evaluation of PTLD cell extinction is necessary to maintain graft function with adequate immunosuppression thereafter.

Adult↗

Characterization of dental epithelial progenitor cells derived from cervical-loop epithelium in a rat lower incisor.

Dental epithelial progenitor cells differentiate into various cell types during development of tooth germs. To study this mechanism, we produced immortalized dental epithelial progenitor cells derived from the cervical-loop epithelium of a rat lower incisor. The expression patterns of cytokeratin 14, nerve growth factor receptor p75, amelogenin, Notch2, and alkaline phosphatase were examined by immunohistochemistry in both lower and higher cell densities. The patterns of each were compared in the dental epithelium of rat lower incisors. The results demonstrated that these cells could produce ameloblast lineage cells, stratum intermedium cells, stellate reticulum, and outer enamel epithelium. Furthermore, fibroblast growth factor 10 stimulated proliferation of dental progenitor cells and subsequently increased the number of cells expressing alkaline phosphatase. These results suggest that fibroblast growth factor 10 plays a role in coupling mitogenesis of the cervical-loop cells and the production of stratum intermedium cells in rat incisors.

Alkaline Phosphatase↗

Activation of Na+-independent Mg2+ efflux by 20-hydroxyeicosatetraenoic acid in rat renal epithelial cells.

Renal epithelial cells may have Mg(2+) transport pathways that regulate intracellular free Mg(2+) concentration ([Mg(2+)](i)) and reabsorption into the body. In mag-fura 2 fluorescent measurement, extracellular Mg(2+) removal induced a Na(+)-independent [Mg(2+)](i) decrease. The [Mg(2+)](i) decrease was suppressed by methyl arachidonyl fluorophosphonate, a cytosolic and Ca(2+)-independent phospholipase A(2) (iPLA(2)) inhibitor, and bromoenol lactone, an iPLA(2) inhibitor, but it was not suppressed by a secretory phospholipase A(2) inhibitor. On the contrary, the [Mg(2+)](i) decrease was enhanced by the addition of exogenous arachidonic acid (AA). Next, we examined the effect of AA metabolite inhibitors on the [Mg(2+)](i) decrease. 17-octadecynoic acid inhibited the [Mg(2+)](i) decrease, but indomethacin and nordihydroguaiaretic acid did not. In the 17-octadecynoic acid-treated cells, 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoic acid (20-HETE) recovered the [Mg(2+)](i) decrease. Nicardipine inhibited both the basal and the 20-HETE-enhanced [Mg(2+)](i) decrease. These results suggest that 20-HETE is a key mediator in the activation of Na(+)-independent Mg(2+) efflux.

Animals↗

Process performance and change in sludge characteristics during anaerobic digestion of sewage sludge with ozonation.

A new process configuration combining anaerobic digestion with ozonation, and operated at long SRT, was studied with the objective of on-site reduction in sludge quantity and improving biogas recovery. The process performance with respect to solid reduction efficiency and other important process parameters like accumulation of inorganic solids, changes in sludge viscosity and dewatering characteristics were evaluated from the data of long term pilot scale continuous experiments conducted using a mixture of primary and secondary municipal sewage sludge. Due to sludge ozonation and long SRT, high VSS degradation efficiency of approximately 80% was achieved at a reactor solid concentration of 6.5%. A high fraction of inorganic solid (>50%) consisting mainly of acid insoluble and iron compounds was found to accumulate in the reactor. The high inorganic content accumulated in the digested sludge did not, however, contribute to the observed increase in sludge viscosity at high solid concentration. The sludge viscosity was largely found to depend on the organic solid concentration rather than the total solid content. Moreover, higher inorganic content in the digested sludge resulted in better sludge dewaterability. For a quick assessment of the economic feasibility of the new process, an economic index based on the unit cost of digested sludge disposal to unit electric cost is proposed.

Bacteria, Anaerobic↗

Quantification of amoA gene abundance and their amoA mRNA levels in activated sludge by real-time PCR.

The transcription level of amoA mRNA encoding a subunit of ammonia monooxygenase (AMO) in ammonia-oxidizing bacteria (AOB) was quantified by reverse transcription-polymerase chain reaction (RT-PCR) methods in combination with real-time PCR technology. The effects of ammonia concentration and dissolved oxygen (DO) on the transcription levels of amoA mRNA and 16S rRNA in AOB were evaluated in batch experiments with nitrifying sludge taken from a lab-scale reactor treating artificial wastewater. A batch incubation without ammonia resulted in a rapid decrease, within four hours, in the transcription level of amoA mRNA to as low as 1/10 of that at the beginning of the experiment, while the 16S rRNA level in AOB was almost constant. After subsequent incubation with 3 mM ammonia for eight hours, a small increase in the transcription level of amoA mRNA occurred, but ammonia oxidation proceeded in the interim. Copy numbers of amoA mRNA showed an almost fixed value for over eight hours in the absence of dissolved oxygen.

Ammonia↗

Gemcitabine and vinorelbine followed by docetaxel in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02).

To evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC), we conducted the multiinstitutional phase II study. A total of 44 chemotherapy-naive patients with advanced NSCLC were treated with GEM 1000 mg m(-2) and VNR 25 mg m(-2) intravenously on days 1 and 8 every 3 weeks for three cycles. DOC 60 mg m(-2) was then administrated intravenously at 3-week intervals for three cycles. Patients were evaluated for response and toxicity with each cycle of the treatment. The major objective response rate was 47.7% (95% confidence interval (CI), 33.8-62.1%). Median survival time (MST) was 15.7 months and 1-year survival rate was 59%. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 36.3%, grade 3/4 anaemia in two patients (4.5%) and grade 3 thrombocytopenia in one patient (2.3%). Grade 3 pneumonitis occurred in two patients (4.5%) in GEM/VNR cycles. In the DOC cycles, grade 3/4 neutropenia occurred in 39.4% but no patient experienced grade 3/4 anaemia or thrombocytopenia. Of the 44 eligible patients, 33 patients completed three cycles of GEM/VNR and 22 patients completed six cycles of planned chemotherapy (three cycles of GEM/VNR followed by three cycles of DOC). The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by DOC, and was very active and well tolerated. This study forms the basis for an ongoing phase III trial that compares this nonplatinum triplet and standard platinum doublet combination (carboplatin/paclitaxel).

Adult↗

Acetate synthesis from H2/CO2 in simulated and actual landfill samples.

To investigate the characteristics of biological decomposition in a municipal solid waste landfill, laboratory simulated samples and full-scale actual samples excavated from landfills in Taiwan were used. Nitrogen gas was produced continuously in the simulated samples. Although nitrate or nitrite could not be detected in the leachate, this did not indicate that nitrate or nitrite was not available in the solid waste. Landfills both produce and consume H2 under anaerobic conditions. In the suspension experiment, where H2/CO2 were used as substrate, significant acetate concentration accumulated concomitantly along with hydrogen consumption. Relatively low production of methane was observed in both the simulated sample and actual samples. Collectively, acetate synthesis was the dominant reaction in the simulated sample and actual samples for hydrogen consumption. This study was the first paper reporting that the homoacetogenesis was the significant process in the landfill for hydrogen utilization, which was validated by the consumption of 4.01-5.43 moles of hydrogen per mole acetate formed. The significant acetate accumulation indicated that the homoacetogens outcompeted the hydrogentrophic methanogens in the landfill samples. Metabolically versatile homoacetogens can use many more substrates simultaneously than their competitor which is bound only to a very few substrates. Themetabolic versatility of homoacetogens could be the main reason for their success in the landfill

Acetates↗

New approaches to the understanding of tamoxifen action and resistance.

Tamoxifen (TAM) provides an effective agent for treatment of hormone-dependent breast cancer but resistance uniformly ensues upon continued use. Additional studies are required to define more precisely the mechanisms involved in development of resistance. We conducted systematic experimental and clinical studies based on the hypothesis that tumors exposed to TAM long-term may develop resistance by becoming hypersensitive to its estrogenic effects. These investigations uncovered new features of the TAM resistance (TR) phenomenon and identified possible means for its prevention and/or elimination. Initially we confirmed that TR may be divided into two subtypes, primary and acquired resistance, and that these differ by certain important characteristics including the level of the possible involvement of adaptive and genetic components. Then we distinguished at least three consequent stages of this phenomenon: stage I when TAM behaves as an antiestrogen, stage II with development of increased sensitivity to the agonistic (pro-estrogenic) properties of TAM and stage III with an adaptive increase in sensitivity to estradiol (E(2)). During this evolutionary process, as shown in vitro, MAP kinase (MAPK) and aromatase activities increase. The time frame of the increase in MAPK activity as a rule outpaces the increase in aromatase activity during the course of the development of TR. This may occur as a response to estrogen deprivation or interruption of the process of estrogen signaling and can be one of the promoting factors of increased aromatase activation. On the other hand, the chronology of these events indicates that changes in the MAPK cascade can be more important for the early steps of the development and maintenance of the TR state. Changes in local estrogen production/sensitivity to E(2) are perhaps essential for the later steps of this phenomenon. We have explored the use of a growth factor-blocking agent to abrogate the adaptive changes in sensitivity. Farnesylthiosalicylic acid (FTS), an inhibitor of GTP-Ras binding to its membrane acceptor site, reduces the increase in the number of MCF-7 cells induced by long-term TAM treatment. It also decreases MAPK activity in TAM-treated MCF-7 cells and in established TR cell lines. Alone or in combination with letrozole (presumably, through the influence on MAPK pathway) FTS exerts moderate inhibitory effects on aromatase activity in estrogen-deprived or estrogen-exposed MCF-7 cells. Taken together, our observations suggest that FTS is a 'candidate drug' for the treatment of TR. Both the adaptive and genetic types of resistance may be amenable to this approach. Our studies underline the possible importance of starting the treatment/prevention of TR early on. From our clinical studies using immunohistochemistry, there is a rather strong rationale to include as a predisposing factor in the development of TR the increase in MAPK and aromatase activities in human primary breast tumors. In summary, data obtained during the course of this project may be considered as evidence supporting the principle that processes resulting in responses to TAM as an agonist and the development of estrogen hypersensitivity of breast cancer cells could potentially be mechanistically linked.

Animals↗

[The stratification of surgically treated T4 (stage IIIb) primary lung cancers; analysis of cases with intrapulmonary metastases in the same lobe as the primary tumors (pm 1) and invading adjacent organs].

OBJECTIVE: The purpose of this article was to investigate the validity of T4 classification of primary non-small cell lung cancer. METHODS: We retrospectively reviewed the clinical outcome of cases with pm 1 (n = 65) and T4 tumors invading adjacent organs (n = 36). RESULTS: When the pm 1 tumors were excised completely (n = 57), the prognosis of these cases was affected by the pN factor (5-year survival rate: pN 0-1; 70.1%, pN 2-3; 7.7%, p = 0.0002) and comparable to that of T2 diseases (pN 0-1 cases: p = 0.7315). The patients who underwent complete resection for their pm 1 tumors had a significantly better prognosis than cases with disseminations or malignant pleural effusions which had the same T4 classification (p < 0.0001). The prognosis of the patients who underwent complete resection for the tumors invading adjacent organs (classified under T4) was similar to that of T3 diseases (pN 0-1 cases: p = 0.7116). CONCLUSIONS: Patients whose lung cancer is classified as T4 comprise 2 subgroups; those whose tumors can be completely resected, and those in whom complete resection is impractical. There is a significant difference in the management and the prognosis between these 2 groups although they share the same T4 classification.

Adolescent↗