Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 37 records · Page 2Linked to original sources

PubMed2005

Pathology of experimental disuse muscular atrophy in rats.

The relationship between structural changes and hyaluronic acid (HA) content in muscular atrophy is unknown. The objective of our study was to conduct multifaceted evaluations of the change in muscle extensibility in muscular atrophy, in terms of morphological aspects as well as from a biochemical viewpoint, including changes in intercellular substances. Using a muscular atrophy model of the soleus muscle in the cast-fixed limbs of Wistar rats, we examined changes in HA accompanying muscular atrophy. Compared with controls, the cast-fixed limbs showed histological evidence of muscular atrophy and electron microscopy indicated destruction of the fasciae. Measurement of the HA level in muscle tissue from cast-fixed rats indicated a reduction in concentration per unit of weight. In contrast, serum HA concentrations increased in the cast-fixed group compared with the control group, suggesting that HA present in the fasciae was released into the blood stream during muscular atrophy.

Animals↗

PubMed2005

HLA-haploidentical nonmyeloablative stem cell transplantation: induction to tolerance without passing through mixed chimaerism.

There are few reports of unmanipulated HLA-haploidentical nonmyeloablative stem cell transplantation (NST) using only pharmacological acute graft-vs.-host disease (GVHD) prophylaxis. We present here a successful case of unmanipulated HLA-haploidentical NST for mediastinal large B cell lymphoma that was resistant to autologous peripheral blood stem cell transplantation (PBSCT). The conditioning regimen consisted of fludarabine, busulfan and rabbit anti-T-lymphocyte globulin (ATG) in addition to rituximab. GVHD prophylaxis was performed using tacrolimus and methylprednisolone 1 mg/kg. The patient had rapid engraftment, with 100% donor chimaerism in the lineages of both T cells and granulocytes on day +12, but developed no GVHD clinically. The patient is still in complete remission past day +1020, with no sign of chronic GVHD without receiving immunosuppressive agents. HLA-haploidentical NST may be performed without utilizing mixed chimaerism.

Adult↗

PubMed2005

Effects of agar (kanten) diet on obese patients with impaired glucose tolerance and type 2 diabetes.

AIM: The aim of this study was to evaluate the efficacy of agar diet in combination with a conventional diet (traditional Japanese food) for obese patients with impaired glucose tolerance and type 2 diabetes. METHODS: After a 4-week run-in period on their habitual diets, 76 patients were randomly assigned to have conventional diet or conventional diet with agar. Both groups were on these diets for 12 weeks. Body weight, body mass index (BMI), glycaemic control, blood pressure, insulin resistance, total body fat, fat distribution and lipids were assessed before and after the experimental period. RESULTS: In both groups, after 12 weeks, mean body weight, BMI, fasting glucose levels, homeostasis model assessment-insulin resistance, and systolic and diastolic blood pressures had decreased significantly from their baseline values. HbA(1)c, visceral fat area, subcutaneous fat area, total body fat, insulin area under the curve after oral glucose tolerance test and total cholesterol decreased significantly in the agar-diet group. After 12 weeks, mean changes of body weight (-2.8 +/- 2.7 kg vs. -1.3 +/- 2.3 kg, p = 0.008), BMI values (-1.1 +/- 1.1 kg/m(2) vs. -0.5 +/- 0.9 kg/m(2), p = 0.009) and total cholesterol (-7.6 +/- 27.5 mg/dl vs. + 2.4 +/- 23.4 mg/dl, p = 0.036) were significantly greater in the agar-diet group than in the conventional diet group. CONCLUSIONS: The agar diet resulted in marked weight loss due to the maintenance of reduced calorie intake and to an improvement in metabolic parameters.

Agar↗

PubMed2004

Quantum suppression of microwave ionization of Rydberg atoms at high scaled frequency.

Microwave ionization of Rydberg atoms is well described as the onset of classical chaos when the microwave frequency omega is less than the Kepler frequency 1/n(3). However, when omega>1/n(3), i.e., at high scaled frequency Omega=omegan(3)>1, classical ionization is predicted to be suppressed by quantum interference, an analogue to Anderson localization in a solid. Using 17.55 GHz microwave fields we have observed the ionization of Sr Rydberg atoms in the regime 1</=Omega</=5 . Our measurements demonstrate the quantum suppression of classical diffusive ionization and show the ionization field to be n independent in this regime.

Journal Article↗

PubMed2004

Nondispersing wave packets.

We have formed nondispersing wave packets from atomic Li Rydberg eigenstates by adding a small microwave field approximately resonant with the Deltan=1 transition. The orbital motion of the Rydberg electron in states of 70<or=n<or=78 becomes phase locked to a 17.5 GHz microwave field and remains so for 900 ns, roughly 15 000 orbits of the Rydberg electron. A Floquet approach provides a reasonable quantum-mechanical description.

Journal Article↗

PubMed2004

Extended sigmoid-shaped free jejunal patch for reconstruction of the oral base and pharynx after total glossectomy with laryngectomy.

The procedure for reconstruction of the extensive defect after total glossectomy with total laryngectomy has not been standardised so far. We have devised a new method in which a free jejunal patch is extended to a sigmoid-shaped form specifically optimised for reconstruction of the defect that consists of the entire floor of the mouth and the antero-lateral walls of the pharyngoesophageal tract. After a jejunal segment of about 40 cm has been longitudinally opened in full length, the proximal quarter is folded parallel to the second quarter, which is then folded parallel to the third quarter in the opposite direction, to be laid out in a S-shaped form. Side-by-side sutures are then placed along each of the folded borders and corrective trimming is done to fit the defect. This widely extended patch replaces the whole oral base, whereas the remaining distal quarter of the patch replaces the antero-lateral walls of the hypopharynx and cervical esophagus. Because of the encouraging functional results with satisfactory restoration of oral alimentation, this procedure is considered to be ideal for the reconstruction of the defect which follows total glossectomy with total laryngectomy.

Adult↗

PubMed2004

Fatal hypothermia related vacuolation of hormone-producing cells in the anterior pituitary.

We found small cytoplasmic vacuoles in the hormone-producing cells of anterior pituitary in hypothermic death. The vacuoles were found in approximately 40% of anterior pituitary cells both in males and females that had died from cold (n=31) while the detection rate was lower than 1% (P <0.001) in the other causes of death (n=180: fire death, n=25; fatal injury, n=24; asphyxia, n=24; poisoning, n=8; natural diseases, n=103). The detection rate in hypothermic death was the highest in ACTH cells (about 65%), followed by gonadotrophs (about 43%), and the lowest in TSH cells (about 16%) (P <0.001). These findings suggest that the cytoplasmic vacuoles in the anterior pituitary cells may be the most closely related to cold exposure among the above-mentioned cause of death, providing a supplementary evidence for determining the causes of death.

Adrenocorticotropic Hormone↗

PubMed2004

Epidermal growth factor and insulin inhibit cell death in pancreatic beta cells by activation of PI3-kinase/AKT signaling pathway under oxidative stress.

Production of reactive oxygen species (ROS) during islet purification by enzymatic digestion as well as during warm and cold ischemia causes islet cell damage. Recent reports have shown that activated Akt, the downstream protein after phosphatidylinositol (PI) 3-kinase, is involved in cell survival by phosphorylating several proteins that mediate apoptosis. We analyzed the role of PI3-kinase/Akt pathway activation using insulin or epidermal growth factor (EGF) on islet beta cell survival during oxidative stress. Canine islets and murine beta cell line (BTC) were cultured in the presence of hydrogen peroxide (H(2)O(2)) for 12 to 20 hours. Viability and cell death were measured by MTT assay. Maximum cell damage was observed with as little as 100 micromol/L of H(2)O(2). Pretreatment with 100 ng/mL of insulin significantly decreased cell damage. Meanwhile, the protective effect of insulin was partially blocked with an inhibitor of PI3-kinase, LY294002, suggesting the utilization of PI3-kinase/Akt signaling pathway for the observed cytoprotective effect. Similar to insulin, EGF also protected beta cells from oxidative stress. Our results suggest that PI3-kinase/Akt activation by insulin or EGF is beneficial for islet beta cell protection.

Adult↗

PubMed2004

In vivo studies of signaling in rod pathways of the mouse using the electroretinogram.

PURPOSE: (a) To examine the possibility that there is a threshold in the synaptic mechanism linking rods to rod bipolar cells that can reduce the transmission of continuous noise from the rods without blocking the transmission of any significant proportion of single-photon responses. (b) To estimate the level of this threshold and the amplitude of the continuous noise which it can serve to reduce. (c) To identify the location of the threshold mechanism in the rod to rod bipolar cell pathway. METHODS: Corneal electroretinogram recordings were made from dark-adapted mice anesthetized with ketamine/xylazine after inner-retinal components had been suppressed to isolate PII, the response of depolarizing bipolar cells. Suppression was achieved by intravitreal injections of GABA, TTX, or in Cx36 KO animals by crushing the optic nerve and waiting for ganglion cells to degenerate. RESULTS: All energy-scaled records of isolated PII obtained with ganzfeld stimuli that gave rise to much less than one photoisomerization (R*) per rod (0.01-0.2 R*/rod), had an essentially identical waveform. Stronger stimuli caused a reduction in the peak amplitude of energy-scaled records (saturation) and stimuli strong enough to produce multiple isomerizations in individual rods resulted in a shortening of the response latency and an increase of the energy-scaled amplitude at early times (supralinearity). The shape of the rising edge of isolated PII changed with flash energy in a way that was consistent with the existence of a synaptic threshold whose level was less than one tenth of the amplitude of single-photon signals and a continuous noise whose rms amplitude was even less than this. However, when measured at the time of the peak, the amplitude of PII increased linearly in proportion to stimulus energy from the very lowest levels up to the point where there was, on average, 0.2 R*/rod. CONCLUSIONS: There is a threshold nonlinearity operating at the output of the rod to rod bipolar cell synapse that can usefully reduce the transmission of continuous rod noise without significantly affecting the transmission of single-photon signals. This nonlinearity does not affect the overall linear function of the rod pathway at levels at which it is effectively operating in a photon-counting mode.

Animals↗

PubMed2004

Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment.

Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. Biliverdin is subsequently reduced to bilirubin by the enzyme biliverdin reductase. Increasing evidence has indicated the critical role of HO-1 in cytoprotection and more diverse biological functions. Induction of HO-1 by various chemical inducers that are primarily cell stress inducers or by HO-1 gene transfection confers a protective capacity to cultured cells as well as to cells in several in vivo animal models. In addition, HO-1-deficient mice exhibit a significant increase in susceptibility to tissue injury. The cytoprotective action of HO-1 seems to be mainly a function of the antiapoptotic effects of the enzyme. HO-1 is believed to exert this antiapoptotic action by multiple mechanisms: (a) decreased intracellular pro-oxidant levels, (b) increased bilirubin levels, and (c) elevated CO production. CO may produce an antiapoptotic effect by inhibiting both expression of p53 and release of mitochondrial cytochrome c. HO-1 may also be a target in antitumor therapy because the growth of most tumors depends on HO-1. Our preliminary studies with an HO inhibitor showed a promising antitumor effect. This preliminary work warrants continued investigation for possible novel anticancer chemotherapy.

Antineoplastic Agents↗

PubMed2004

Effect of peripheral blood progenitor cell dose on hematopoietic recovery: identification of minimal progenitor cell requirements for rapid engraftment.

Repeated high-dose chemotherapy (HDC) with stem cell support is advocated for curative treatment of epithelial ovarian cancer patients, requiring large quantities of progenitor cell harvest. Although the switchover to peripheral blood stem cell transplantation has generally made possible the harvest of large quantities of progenitor cells, the minimum threshold is still pertinent for planning the safe conduct of HDC. However, as the minimum threshold for safe peripheral blood stem cell transplantation (PBSCT) is not yet established, this study was designed to clarify the minimum amount of progenitor cells required for prompt recovery of hematopoietic. Retrospective analysis was performed on 52 HDCs administered in 37 ovarian cancer patients. After autologous bone marrow aspiration (10 patients) or peripheral blood stem cell harvest (27 patients), colony-forming unit granulocyte macrophage (CFU-GM) were enumerated prior to cryopreservation. Numbers of CFU-GM were again calculated before reinfusion and the patients were divided into eight groups: 0.13-<0.4, 0.4-<0.7, 0.7-<1.0, 1.0-<3.5, 3.5-<5.0, 5.0-<10.0, 10.0-<20.0 and >20.0 (x 10(5)/kg). The minimum CFU-GM threshold (x 10(5)/kg) was found to be 1.0-<3.5 for platelets and 3.5-<5.0 for white blood cells. Higher infusion doses did not lead to significant benefits in hematopoietic reconstruction. These results indicate that preservation of a minimum of 7-10 x 10(5)/kg CFU-GM is recommended for the safe conduct of tandem HDCs.

Female↗

PubMed2004

Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine.

Clinical application of anticancer agents has been often hampered by toxicity against normal cells, so the achievement of their cancer-specific action is still one of the major challenges to be addressed. Previously, we reported that arsenic trioxide (As2O3) could be a promising new drug against not only leukemia but also solid tumors. The cytotoxicity of As2O3 occurred through the generation of reactive oxygen species (ROS), thus inhibiting radical scavenging systems would enhance the therapeutic efficacy of As2O3 provided that normal cells were relatively resistant to such a measure. Here, we report that the combination therapy of As2O3 with L-buthionine-sulfoximine (BSO), which inhibits a critical step in glutathione synthesis, effectively enhanced in vitro growth inhibition effect of As2O3 on all 11 investigated cell lines arising from prostate, breast, lung, colon, cervix, bladder, and kidney cancers, compared with As2O3 treatment alone. Furthermore, this combination enhanced cytotoxicity to cell lines from prostate cancer with less toxicity to those from normal prostate. In vitro cytotoxic assay using ROS-related compounds demonstrated that hydrogen peroxide (H2O2) is a major cytotoxic mediator among ROS molecules. Biochemical analysis showed that combined use of As2O3 and BSO blocked H2O2-scavenging systems including glutathione, catalase, and glutathione peroxidase, and that the degree of this blockade was well correlated with intracellular ROS levels and sensitivity to this treatment. Finally, the effectiveness of the combination therapy of As2O3 with BSO was demonstrated with an orthotopic model of prostate cancer metastasis. We propose that the combination therapy of As2O3 with BSO is a valid means of blockade of H2O2-scavenging system, and that the combination of a ROS-generating agent with an inhibitor of major scavenging systems is effective in terms of both efficacy and selectivity. Furthermore, because the effective doses of both compounds are within clinically achievable range, this report will lead to immediate benefit for the development of a new cancer therapy.

Animals↗

PubMed2004

Hemi-clamshell approach for advanced primary lung cancer.

BACKGROUND: The hemi-clamshell approach provides a wide anterior view of the mediastinum, apical dome, and cervicothoracic area. However, only a few reports have been made regarding this technique. METHODS: The hemi-clamshell approach was used in 24 patients, of whom 5 had a Pancoast tumor, 15 had mediastinal involvement, and 4 underwent mediastinal lymphadenopathy for left-sided lung cancer. Twenty-one of the patients received preoperative therapy. RESULTS: Twenty-one operations were complete resections. In addition, 12 patients received cardio-vascular reconstruction and 5 a first rib resection. Postoperative major morbidity was 21 % (6/24) and mortality was 4.2 % (1/24). Nine patients died of systemic tumor relapse and 14 patients were alive after a median follow-up of 24 months (range 3 - 68 months) following the initial therapy. The 5-year survival rate of patients with mediastinal involvement was 37 % and that of 13 patients with postoperative stage I or II was 35 %. CONCLUSIONS: The hemi-clamshell approach provides a wide exposure allowing a safe and complete removal of lung cancer that involves the mediastinum and apical thoracic dome, leading to a better long-term survival rate for patients with this disease.

Adenocarcinoma↗

PubMed2004

A polymorphism of DRD2 gene and brain atrophy in methamphetamine psychosis.

Our group, Ujike et al., recently reported that the A1 allele of TaqI A polymorphism of the dopamine receptor D2 (DRD2) gene, associated with transient psychosis, significantly differs from that of patients with prolonged psychosis in methamphetamine psychosis. Therefore, we examined the association between the TaqI A polymorphism of the DRD2 gene and the brain MRI view for patients with methamphetamine psychosis. The subjects underwent brain MRI scans using the FLAIR method. Genotyping was performed by PCR-RFLP methods using genomic DNA extracted from peripheral blood by the phenol method. Ten subjects had the A1/A2 genotype, eleven subjects had the A2/A2 genotype, and no subject had the A1/A1 genotype. The domain size, including the thalamus and basal ganglia that were inside each side of the putamens, did not differ between the three groups (the A1/A2-group, the A2/A2-group, and the young healthy person group). In the comparison based on this domain, the temporal lobe tended to narrow in the A2/A2-group compared to the A1/A2-group (P = .06). The other domain (cerebrum, corpus callosum, etc.) showed no difference between the A1/A2-group and the A2/A2-group. It is suggested that in methamphetamine psychosis the TaqI A polymorphism not only regulates prolongation of psychosis symptoms but also influences the form of the temporal lobe.

Adult↗

PubMed2004

Absence of mutations in the Wilms' tumor gene wt1 in de novo non-small cell lung cancers.

We recently demonstrated that the WT1 gene was overexpressed in the majority of de novo lung cancers regardless of cancer subtypes. Here, we examined WT1 genomic DNA in 38 cases of de novo non-small cell lung cancers (NSCLC) for mutations using direct sequencing. The sequencing analysis showed no mutations of WT1 genomic DNA in any of 38 de novo non-small cell lung cancers examined. These results indicated that the non-mutated, wild-type WT1 gene played an important role in de novo NSCLC.

Adult↗

PubMed2003

Design of controlled-release formulation for ivermectin using silicone.

The purpose of this study was to design a formulation using silicone as carrier, so that release of ivermectin (IVM) can be controlled for a long period of time. The lateral side of a cylindrical matrix-type formulation composed of IVM and silicone was covered with silicone to obtain a covered-rod (CR) formulation. With this formulation, linear release of IVM was obtained. With addition of polyethylene glycol 4000 (PEG), release of IVM was accelerated. In a trial with subcutaneous administration to mice, blood concentration of IVM was maintained within one-order over a period of 3 months. The velocity of release of IVM from CR preparation depended on the change in solubility of IVM by additives, and in the case of a formulation with addition of desoxycholate sodium, linear in vitro release of IVM was observed over a period of 1 year.

Administration, Cutaneous↗

PubMed2003

Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour.

Induction of haem oxygenase-1 (HO-1) may provide an important protective effect for cells against oxidative stress. Here, we investigated the mechanism of cytoprotection of HO-1 in solid tumour with a focus on the antiapoptotic activity of HO-1. Treatment of rat hepatoma AH136B cells with the HO inhibitor zinc protoporphyrin IX (ZnPP IX) or tin protoporphyrin IX resulted in extensive apoptotic changes of tumour cells both in vivo and in vitro. Caspase-3 activity of the ZnPP IX-treated hepatoma cells increased significantly. Moreover, ZnPP IX-induced apoptosis was completely inhibited by simultaneous incubation with a specific caspase-3 inhibitor and was partially abrogated by bilirubin, a reaction product of HO. In vivo ZnPP IX treatment did not affect nitric oxide (NO) production and tumour blood flow. Western blot analyses showed that HO-1 expression in AH136B cells was strongly upregulated by NO donors, for example, S-nitroso-N-acetyl penicillamine and propylamine NONOate in vitro; conversely, it was remarkably reduced in vivo by pharmacological blockade of NOS. We conclude that HO-1 may function in antiapoptotic defense of the tumour, and thus it may have important protective and beneficial effects for tumour cells against oxidative stress induced by NO, which is produced in excess during solid tumour growth in vivo.

Animals↗

PubMed2003

Soluble soybean fiber: a 3-month dietary toxicity study in rats.

Soluble soybean fiber (SSF) is a food ingredient intended for human consumption. SSF was administered in the diet to Sprague-Dawley CD(R) rats at concentrations up to 40,000 ppm for three months. Unformed stool was detected during the early and middle part of the treatment period and was considered an exaggeration of a normal physiological response to the fibre content in the diets, to which the animals appeared to adapt. This finding has been reported with other water-soluble fibres and was not considered an adverse effect. Decreased weight gain and food intake during the first half of the treatment period are possible sequelae of increased intestinal throughput. Adaptation was indicated by subsequently improved weight gain and food consumption. Decreased serum cholesterol occurred in males receiving 30,000 or 40,000 ppm and this has been reported before in rats fed soluble fibre. Haemoconcentration (indicated by increased erythrocyte count, haematocrit and haemoglobin concentration) and decreased spleen weight are likely related to minor fluid imbalances during exposure to high concentrations of dietary fibre and occurred at all SSF concentrations. The spleen was microscopically normal. In conclusion, the no-observed-adverse-effect level (NOAEL) for SSF in this study was 40,000 ppm (equivalent to 2.43 g/kg bodyweight/day for males and 2.91 g/kg bodyweight for females).

Adaptation, Physiological↗