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Biomedical subjects

Y Yamada

Publications and source records attributed to Y Yamada.

At least 19 recordsLinked to original sources

Oral behavior from food intake until terminal swallow.

We analyzed oral behavior from food intake until terminal swallow for mastication and swallowing under a freely eating condition with a natural food. Measurements, including movement of the mandible and tongue, the size of the gape, different sequences involved in the oral aspect of the swallowing action, and bolus size and movement were carried out in five "freely eating subjects" using videofluorography. During food intake, the tongue moved forwards and backwards to introduce food into the mouth, to compress the food against the hard palate, and to transport food to the occlusal surface of the molar teeth. Most of the food was swallowed in the first swallow, and any residual food was aggregated by the tongue into a bolus and then swallowed in the last swallow. These findings suggest that 1) tongue manipulation plays an important role in recognizing and evaluating the volume of bite taken, 2) the intra-oral compression of food has a role in the recognition of food texture, 3) stage I transport is closely bound to the texture recognition process, 4) humans need at least two swallows, even with one bite of food, when ingesting food freely, and 5) the duration time of the oral stage of swallowing may depend on the bolus volume and be longer for smaller volumes unlike those measured under the command swallow.

Adult↗

Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets.

We have established a new method for allogeneic pancreatic islet (PI) transplantation: relatively low doses of irradiation followed by simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In the present study, we have compared this method with intra-bone marrow (IBM)-bone marrow transplantation (BMT), and with a combination of both methods. Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 (F344, RT1A(l), RT1B(l)), were irradiated 1 day before transplantation. PIs of Brown Norway rats (BN, RT1A(n), RT1B(n)) were transplanted into the liver of the diabetic F344 rats via the PV. BMCs from BN rats were injected into the recipients' bone marrow (IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM (PV+IBM). We compared graft survival among the groups of '9 Gy+IBM'(10/10 accepted), '9 Gy+PV'(7/10 accepted), '9 Gy+IV'(0/7 accepted), '9 Gy+PV+IBM'(8/8 accepted), '8.5 Gy+IBM'(4/9 accepted), '8.5 Gy+PV'(0/7 accepted), '8.5 Gy+IV'(0/7 accepted), '8.5 Gy+PV+IBM'(9/12 accepted), '8 Gy+IBM'(2/10 accepted) and '8 Gy+PV+IBM'(2/8 accepted). As we reported previously, PV-BMT is more effective in inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires less pretreatment than PV-BMT. (PV+IBM)-BMT was found to be the most effective in inducing the acceptance of allogeneic PIs. These results suggest that allogeneic PI-transplantation in conjunction with (PV+IBM)-BMT could become a viable strategy.

Animals↗

A genomic analysis of adult T-cell leukemia.

Adult T-cell leukemia (ATL) is an intractable malignancy of CD4+ T cells that is etiologically associated with infection by human T-cell leukemia virus-type I. Most individuals in the chronic stage of ATL eventually undergo progression to a highly aggressive acute stage. To clarify the mechanism responsible for this stage progression, we isolated CD4+ cells from individuals in the chronic (n=19) or acute (n=22) stages of ATL and subjected them to profiling of gene expression with DNA microarrays containing >44,000 probe sets. Changes in chromosome copy number were also examined for 24 cell specimens with the use of microarrays harboring approximately 50,000 probe sets. Stage-dependent changes in gene expression profile and chromosome copy number were apparent. Furthermore, expression of the gene for MET, a receptor tyrosine kinase for hepatocyte growth factor (HGF), was shown to be specific to the acute stage of ATL, and the plasma concentration of HGF was increased in individuals in either the acute or chronic stage. HGF induced proliferation of a MET-positive ATL cell line, and this effect was blocked by antibodies to HGF. The HGF-MET signaling pathway is thus a potential therapeutic target for ATL.

Cell Line, Tumor↗

Fate of cystic ovarian follicles and the subsequent fertility of early postpartum dairy cows.

The fate of cystic ovarian follicles that developed spontaneously during the early postpartum period of 50 lactating dairy cows was traced by ultrasonography to characterise the follicular dynamics in relation to the fertility of the cows. The absence of postpartum ovulations caused by repeated waves of anovulatory large follicles was also characterised and evaluated. Fifteen of the 50 cows developed cystic follicles, and these follicles became follicular cysts in five of the 15 cows. Most of the cystic follicles emerged before the first postpartum ovulation of the cows. The transition from cystic follicles to follicular cysts delayed the cows' first ovulation, oestrus and insemination, but had less influence on their fertility after they had recovered spontaneously. In addition to the 15 cows that developed cystic follicles or follicular cysts, six of the cows had five to 13 waves of follicles before their first ovulation. These repeated waves of follicles caused a more severe delay in the early postpartum reproductive events but did not affect the cows' fertility.

Animals↗

Alveolar cleft osteoplasty using tissue-engineered osteogenic material.

The use of tissue-engineered osteogenic material comprising platelet-rich plasma and autologous mesenchymal stem cells isolated, expanded and induced to osteogenic potential in bone augmentation procedures as a replacement for autologous bone grafts, offers predictable results with minimal donor-site morbidity. This material was applied for an alveolar cleft osteoplasty of a 9-year-old female patient. Serial computed tomograms showed the regenerated bone extending from the cleft walls after 3 months and bridging the cleft after 6 months, with 79.1% of the grafted region after 9 months at the time when the canine and lateral incisor in the affected side erupted in the reconstructed alveolar ridge.

Alveolar Process↗

Phase II study of combination therapy with S-1 and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: A combination of irinotecan with continuous intravenous infusions of 5-fluorouracil (5-FU) and leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. This phase II study evaluated the efficacy and safety of the oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced or recurrent colorectal cancer. PATIENTS AND METHODS: Forty eligible patients with histologically confirmed colorectal adenocarcinoma received this treatment. S-1 was administered orally on days 1 to 14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA < 1.25 m(2)), 50 mg (BSA > or = 1.25 to < 1.50 m(2)), or 60 mg (BSA > or = 1.50 m(2)). Irinotecan (150 mg/m(2)) was administered by intravenous infusion on day 1. RESULTS: A total of 327 courses of treatment were administered to 40 patients. Five patients had complete responses, and 20 had partial responses. The overall response rate was 62.5% (95% confidential interval, 47.5%-77.5%). Median progression-free survival was 8.0 months (95% confidential interval, 5.2-11.4 months). The rates of grade 3 or 4 toxicity were as follows: neutropenia, 15%; anemia, 7.5%; anorexia, 12.5%; and diarrhea, 7.5%. CONCLUSIONS: Combined treatment with S-1 and irinotecan is an effective, well tolerated, and convenient regimen in patients with advanced colorectal cancer. Our findings suggest that combined treatment with S-1 and irinotecan is a promising regimen, offering benefits in terms of safety and survival as compared with conventional regimens in patients with advanced colorectal cancer.

Adenocarcinoma↗

Effect of corosolic acid on postchallenge plasma glucose levels.

Corosolic acid (CRA) is a substance extracted from Lagerstroemia speciosa L. and has been reported to have biological activities in in vitro and experimental animal studies. In this study, 31 subjects were orally administered 10mg CRA or a placebo, on different occasions, in a capsule 5min before the 75-g oral glucose tolerance test (OGTT) in a double-blind and cross-over design. Nineteen subjects had diabetes, seven had impaired glucose tolerance, one had impaired fasting glucose, and four had normal glucose tolerance according to the 1998 WHO criteria. There were no significant differences in plasma glucose levels before and 30min after the administration. CRA treatment subjects showed lower glucose levels from 60min until 120min and reached statistical significance at 90min. In this study, we have shown for the first time that CRA has a lowering effect on postchallenge plasma glucose levels in vivo in humans.

Blood Glucose↗

Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor.

After analysing gene-expression profiles of colon cancers on a cDNA microarray containing cDNAs corresponding to 23 040 human genes, we focused on a gene annotated as C10orf3 (chromosome 10 open reading frame 3), whose expression was elevated in colorectal cancers (CRC) as well as in tumors arising in the stomach, lung, pancreas, and breast. The gene encodes a putative 464-amino-acid protein containing a domain known as AAA (ATPases associated with a variety of cellular activities). Western blot analysis using an antibody to the gene product confirmed that the protein was overexpressed in nine of the 15 clinical cancer tissues examined, compared to corresponding noncancerous epithelial cells. A subsequent proteomics analysis revealed that C10orf3 product associated with the product of tumor susceptibility gene 101 (TSG101), and that C10orf3 downregulated TSG101 in a post-transcriptional manner. Expression of short interfering RNA in cells derived from CRC caused significant decreases in C10orf3 expression and inhibited growth of the transfected cells, which was associated with increased apoptotic cells. These data suggest that elevated C10orf3 expression might play an essential role in the growth of cancer cells, and that suppression of C10orf3-mediated signal transduction may be a novel therapeutic strategy to a wide range of human tumors.

Cell Division↗

Psychopathological features of patients with prolonged anorexia nervosa as assessed by the Minnesota Multiphasic Personality Inventory.

OBJECTIVE: The duration of illness is quite long in some anorexia nervosa (AN) patients. In the present study, we investigated the psychopathological features of patients with prolonged AN as assessed by the Minnesota Multiphasic Personality Inventory-1 (MMPI-1). METHODS: Fifty-five AN patients completed the MMPI-1 on admission to Kyushu University Hospital from 1999 to 2002. The patients were divided into three groups on the basis of their illness duration: a short-term group, less than 5 years of illness duration (n=31); a middle-term group, from 5 to 10 years (n=14); and a prolonged group, 10 years or more (n=10). RESULTS: The prolonged group scored significantly higher on the MPPI-1 scales of hysteria (Hy), low back pain (Lb) and family conflict than the short-term group. DISCUSSION: AN patients whose illness duration was prolonged characteristically had more hysteria with family conflict. This should be considered in their treatment.

Adolescent↗

Small interfering RNA expression vector targeting hypoxia-inducible factor 1 alpha inhibits tumor growth in hepatobiliary and pancreatic cancers.

Hepatobiliary and pancreatic carcinomas are hypovascular tumors that can proliferate under hypoxic conditions. Recent reports have demonstrated that hypoxia-inducible factor 1 alpha (HIF1alpha) plays an important role in the survival of these cancers. Given these findings, the inhibition of the HIF1alpha pathway might prove to be a powerful tool in the treatment of these cancers. To inhibit HIF1alpha expression, we used small interference RNA (siRNA) expression vectors in this study. The transient transfection of siRNA expression vectors significantly reduced both HIF1alpha mRNA levels (13% of control) and protein levels (41% of control) and significantly inhibited the growth of cancer cell lines (P<0.05). VEGF, Glut1, and aldorase A expressions were also significantly reduced by transfection with these vectors (P<0.05), and we found that these vectors induced apoptosis but not cell cycle arrest. In a subcutaneous tumor model using nude mice, transfected MIA PaCa-2 cells, stably expressing siRNAs, barely formed tumors compared to control (P<0.05). This study thus demonstrates the usefulness of siRNA expression vector in targeting HIF1alpha and points to a potential clinical role in the treatment of pancreatic and hepatobiliary carcinomas.

Animals↗

Sensitive and rapid diagnosis of human parvovirus B19 infection by loop-mediated isothermal amplification.

BACKGROUND: Human parvovirus B19 (B19) infections exhibit various skin manifestations that are similar to and hence hard to distinguish from many other skin diseases. The virological diagnosis of B19 infection is usually based on time-consuming serological tests and polymerase chain reaction (PCR). OBJECTIVES: In this study, a DNA amplification method, loop-mediated isothermal amplification (LAMP), was used for the diagnosis of B19 infection and was compared with PCR. METHODS: Ten patients with acute B19 infection and 16 patients with other skin diseases were enrolled. Sera and pharyngeal swabs were used directly as the templates in LAMP. The LAMP reaction was carried out at 63 degrees C for 1 h in a heat block. The reaction products were judged visually, by adding SYBR Green I into the tubes, and by gel electrophoresis. RESULTS: B19 DNA was detected by LAMP in 10 sera and all of seven tested pharyngeal swabs of 10 patients with acute B19 infection but not in samples from 16 patients with other skin diseases. The results were in agreement with those obtained by PCR except for one case. The reason for the single discrepancy may be that the sensitivity of LAMP is 10(2) times higher than PCR. CONCLUSIONS: Detection of B19 DNA by LAMP in serum and especially in the pharynx is a rapid and convenient method for the diagnosis of acute B19 infection.

Acute Disease↗

The alpha4bbeta7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine.

BACKGROUND: Of the numerous adhesion molecules expressed by eosinophils, the alpha4-integrin has been identified as critically involved in eosinophil trafficking in the lung. Most studies have focused on the role of the alpha4beta1-adhesion complex, but eosinophils also express the alpha4beta7-integrin complex. OBJECTIVE: To investigate the role of alpha4beta7, by assessing its membrane expression on eosinophils from different compartments using allergen-challenged mice and IL-4/IL-5 bi-transgenic mice. In addition, we aim to determine the impact of beta7-integrin deficiency on eosinophil recruitment to the lungs and intestine in specific experimental allergic models. RESULTS: Evaluation of alpha4beta7 expression on bronchoalveolar lavage fluid (BALF) and lung tissue eosinophils revealed a down-regulation of this integrin as eosinophils migrate through the lungs. Indeed eosinophils isolated from the BALF and lung of allergic mice had low expression of the alpha4beta7-complex. While expression of the alpha4-chain remained unchanged, a significant decrease in beta7-surface expression was observed. Intestinal eosinophils, isolated from Peyer's patches, also displayed a down-regulation of the alpha4beta7-integrin, albeit only modest. In contrast, circulating eosinophils, isolated from the blood and spleen, expressed high levels of the alpha4beta7-integrin. However, eosinophil trafficking into the lungs of beta7-integrin-deficient mice was not significantly impaired in response to respiratory allergen challenges. In contrast, beta7-deficient mice had impaired eosinophil recruitment to the intestine. CONCLUSION: Taken together, these results identify differential expression of the alpha4beta7-integrin on eosinophils and its critical role in regulating eosinophil responses in the intestine.

Animals↗

Association of epithelial damage and signs of neutrophil mobilization in the airways during acute exacerbations of paediatric asthma.

We examined whether epithelial damage is associated with mobilization of neutrophils or eosinophils in the airway lumen during acute exacerbations of paediatric asthma. Aspirated sputum samples were harvested from 65 paediatric patients (mean age 3.4 +/- 0.4 years) during acute exacerbations of asthma. Patients with signs of infection were excluded. The presence of conglomerates of epithelial cells (i.e. "Creola bodies") in the aspirated sputum was utilized as a marker of epithelial damage. Among the paediatric asthma patients, 60% displayed Creola bodies (CrB+: n = 39) in their sputum samples whereas the remaining patients did not (CrB-: n = 26). CrB+ patients displayed more than a 20-fold increase in the concentration of the neutrophil-mobilizing cytokine interleukin (IL)-8 (pg/ml) and of the neutrophil product neutrophil elastase (NE, g/l), respectively, compared with CrB- patients (IL-8: 7468.2 +/- 1953.6 versus 347.9 +/- 72.6, P < 0.01; NE: 2072.4 +/- 419.0 versus 438.5 +/- 125.7, P < 0.01). Even though not statistically significant, a corresponding trend was observed for the relative number of sputum neutrophils. In contrast, the concentration of the eosinophil-mobilizing cytokine IL-5 and the esoinophil product ECP tended to be lower in CrB+ than in CrB- patients (P > 0.05). In conclusion, as indicated by the analysis of aspirated sputum, epithelial damage is associated with a locally enhanced chemotactic signal for and activity of neutrophils, but not eosinophils, during acute exacerbations of paediatric asthma. It remains to be determined whether these indirect signs of neutrophil mobilization in the airway lumen mirror an increased number of neutrophils in the surrounding airway tissue.

Acute Disease↗

Propofol formulated with long-/medium-chain triglycerides reduces the pain of injection by target controlled infusion.

BACKGROUND: Propofol is a widely used intravenous anesthetic although its injection pain is a common and unpleasant problem. Long-/medium-chain triglyceride (LCT/MCT) propofol has been introduced, as its low free propofol content is expected to reduce injection pain compared with LCT propofol. Target controlled infusion (TCI) differs from conventional induction in the initial infusion pattern. During induction using TCI, we investigated injection pain caused by two propofol solutions with different triglyceride compositions. METHODS: Fifty patients, ASA I-II, with adequate communicative ability, were randomly assigned to two groups. TCI was conducted with Diprifusor for LCT and with BeComSim (custom-made software) for LCT/MCT. The target blood concentration was set at 4 microg/ml for both groups. At 30, 60, and 120 s after the infusion, patients were asked questions regarding the severity of pain on a 0-10 pain score. The total dose of propofol and the time required to induce anesthesia were also investigated. RESULTS: The LCT/MCT propofol group had a larger number of pain-free patients and showed lower severity of pain than the LCT group [the number of pain-free patients being 11 and 3, respectively (P < 0.05), and median maximum pain being 0 and 4.5, respectively (P < 0.01)]. The dose and time required for induction were not significantly different between the groups (dose of 84 +/- 27 and 80 +/- 24 mg, respectively, and time of 119 +/- 60 and 107 +/- 55 s, respectively). CONCLUSION: Our study showed that the frequency and severity of pain during TCI induction with propofol could be significantly reduced using LCT/MCT propofol rather than LCT propofol.

Adult↗

Genetic variations and haplotype structures of the ABCB1 gene in a Japanese population: an expanded haplotype block covering the distal promoter region, and associated ethnic differences.

As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks -1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms -1,789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects.

ATP Binding Cassette Transporter, Subfamily B↗

The inhibition spectrum of solar urticaria suppresses the wheal-flare response following intradermal injection with photo-activated autologous serum but not with compound 48/80.

BACKGROUND: The inhibition spectrum (IS) in solar urticaria was identified mainly in Japanese patients with solar urticaria, although the mechanism of action of the IS has not been elucidated. METHODS: Because an intradermal injection of action spectrum (AS)-irradiated serum in a case of solar urticaria induced a wheal response, we studied the responsiveness of the intradermal injection after an IS irradiation. RESULTS: An AS in this patient was composed of visible light shorter than 500 nm, while an IS was composed of visible light longer than 530 nm. When the IS was exposed immediately after the AS irradiation, the wheal response was inhibited. However, when the IS was exposed before the AS irradiation, the wheal response was not inhibited. An intradermal injection of her serum produced no reaction, whereas an intradermal injection of her serum pre-irradiated with visible light induced a wheal flare response. Further examination revealed that the in vivo wheal-inducing activity of her serum irradiated with visible light could be attenuated by post-IS irradiation at the injection site, while the wheal-inducing activity of her visible light-irradiated serum was not inhibited by irradiation of the activated serum with the IS. The wheal-flare response induced by compound 48/80 and histamine was not altered by IS irradiation at the site of skin tests. CONCLUSION: These findings indicate that photoallergens in the patient's serum that are activated by visible light irradiation are responsible for the development of her symptoms and that the IS may suppress the wheal response by inhibiting the binding of the photoallergens to mast cells, not by inactivating the photoallergens and stabilizing mast cells.

Aged↗

Effects of barbiturates on ATP-sensitive K channels in rat substantia nigra.

ATP-sensitive K channels are widely expressed in cytoplasmic membranes of neurons, and they couple cell metabolism to excitability. They are thought to be involved in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity by hyperpolarizing neurons and reducing excitability. Although barbiturates are often used in patients with brain ischemia, the effects of these agents on neuronal ATP-sensitive K channels have not been clarified. We studied the effects of thiopental and pentobarbital on surface ATP-sensitive K channels in principal neurons of rat substantia nigra pars compacta. Whole cell voltage- and current-clamp recordings were made using rat midbrain slices. ATP-sensitive K channels were activated by intracellular dialysis with an ATP-free pipette solution during perfusion with a glucose-free solution. When the pipette solution contained 4mM ATP and the perfusing solution contained 25 mM glucose, the membrane current at -60 mV remained stable. When intracellular ATP was depleted, hyperpolarization and an outward current developed slowly. Although thiopental did not affect the membrane current in the presence of ATP and glucose, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion at 100 and 300 microM. Thiopental reduced the ATP depletion-induced outward current by 4.7%, 36.7% and 87% at 30, 100 and 300 microM, respectively. The high dose of pentobarbital also exhibited similar effects on ATP-sensitive K channels. These results suggest that barbiturates at high concentrations but not at clinically relevant concentrations inhibit ATP-sensitive K channels activated by intracellular ATP depletion in rat substantia nigra.

Adenosine Triphosphate↗