Biomedical subjects

M Tanaka

Publications and source records attributed to M Tanaka.

At least 91 records · Page 5Linked to original sources

PubMed2004

Inhibition of subgenomic hepatitis C virus RNA in Huh-7 cells: ribavirin induces mutagenesis in HCV RNA.

Hepatitis C virus (HCV) infection is a major problem throughout the world. Combination therapy of interferon (IFN) and ribavirin is the best treatment for eradication at present, but the mechanism is not completely understood. We used the HCV replicon system to investigate this mechanism. The effects of six drugs (UDCA, glycyrrhizin, TJ-9, bezafibrate, ribavirin, and alpha-IFN 2b) on HCV subgenomic RNA (genotype 1b, NS5B 415Y) were examined by reverse transcription polymerase chain reaction, cloning and sequencing. The HCV replication was inhibited by alpha-IFN 2b (7.39-13.2% at 10 U/mL, 3.29-6.12% at 100 U/mL, 1.3-4.86% at 1000 U/mL) and by ribavirin (4.36-13.9% at 100 microg/mL), but not by the other drugs at 24-72 h after treatment. Furthermore, the combination treatment was superior to IFN monotherapy and to ribavirin monotherapy at 72 h post-treatment. Sequence analyses of the double-stranded RNA-activated protein kinase (PKR)-binding domain and flanking regions within the HCV NS5A region revealed that the total numbers of substitutions caused by ribavirin (n = 36) or combination treatment (n = 57) were more than those of IFN alone (n = 5) and controls (n = 6). The HCV replicon system is the most efficient system for HCV replication and is an excellent choice for testing anti-HCV drugs and disinfectants. Our results further suggested that the combination of alpha-IFN 2b and ribavirin might induce mutations, and inhibit HCV RNA synthesis in hepatocytes to a greater extent than ribavirin monotherapy.

Amino Acid Substitution↗

PubMed2004

Effects of nitrous oxide on baroreflex gain and heart rate variability.

BACKGROUND: Spontaneous baroreflex method allows continuous assessment of cardiovagal reflex function within resting blood pressure, but effects of nitrous oxide, per se, on the spontaneous baroreflex response remain unknown. This study was designed to determine the effects of nitrous oxide on spontaneous baroreflex gain and heart rate variability assessed by power spectral analysis in humans. METHODS: Electrocardiogram and non-invasive blood pressure were monitored in 12 healthy volunteers before and during a 15-min inhalation of 67% nitrous oxide in oxygen, while spontaneous respiration was maintained. Least-square regression analysis relating R-R interval and systolic blood pressure was performed to obtain spontaneous baroreflex gains. Heart rate variability was analyzed using fast Fourier transformation. RESULTS: Nitrous oxide did not significantly alter spontaneous baroreflex gains, which correlated well with high-frequency power (0.15-0.4 Hz) of heart rate variability before and during nitrous oxide inhalation. CONCLUSION: Our results indicate that (a) cardiovagal reflex response is not affected by nitrous oxide, per se, and (b) spontaneous baroreflex responses closely reflect beat-to-beat dynamic modulation of the cardiac cycle by the parasympathetic nervous system during inhalation of 67% nitrous oxide.

Adult↗

PubMed2004

Association of ALDH(2) genotypes and alcohol consumption with periodontitis.

There is little information regarding the association between alcohol consumption and periodontitis risk. We assessed whether alcohol consumption and ALDH(2) genotypes were associated with periodontitis. Subjects' lifestyle was examined by a self-administered questionnaire, and the percentage of pocket depths > or = 3.5 mm was used as a periodontal parameter. ALDH(2) genotypes were determined with the use of a PCR/RFLP method. Multiple logistic analyses showed that alcohol consumption was significantly associated with periodontitis, and its odds ratio was 1.98. There was no significant relationship between periodontal status and ALDH(2) genotypes. However, ALDH(2)*1/*2 subjects who consumed > or = 33 g/day of alcohol had a significantly greater percentage of pocket depths > or = 3.5 mm than those whose daily consumption was lower, while there was no significant difference in periodontal status associated with alcohol consumption in ALDH(2)*1/*1 subjects. Our results suggest that alcohol consumption may be a risk indicator for periodontitis in ALDH(2)*1/*2 subjects who consume larger amounts of alcohol.

Adult↗

PubMed2004

Clinical assessment of oral malodor by the electronic nose system.

A recently developed electronic nose has not yet been clinically applied to evaluations of oral malodor. This investigation sought to determine whether an electronic nose could clinically assess oral malodor. Twenty-nine healthy adults and 49 patients were assessed by results of an actual organoleptic test, a score representing malodor strength with an electronic nose in "top-note" mode (top-note score), and measurements of volatile sulfur compound (VSC) concentrations. The correlation coefficient between top-note and actual organoleptic scores (r = 0.71) was comparable with the log VSC and actual organoleptic scores (r = 0.63). However, the area under the receiver-operating characteristic plots for top-note score was significantly larger than that for log VSC. In logistic regression analyses with top-note score as a dependent variable, probing depth, tongue coating, and plaque control record each had independent associations. Our findings suggest that the top-note score from an electronic nose examination may be useful for the clinical evaluation of oral malodor.

Adult↗

PubMed2004

The frictional coefficient of the temporomandibular joint and its dependency on the magnitude and duration of joint loading.

In synovial joints, friction between articular surfaces leads to shear stress within the cartilaginous tissue, which might result in tissue rupture and failure. Joint friction depends on synovial lubrication of the articular surfaces, which can be altered due to compressive loading. Therefore, we hypothesized that the frictional coefficient of the temporomandibular joint (TMJ) is affected by the magnitude and duration of loading. We tested this by measuring the frictional coefficient in 20 intact porcine TMJs using a pendulum-type friction tester. The mean frictional coefficient was 0.0145 (SD 0.0027) after a constant loading of 50 N during 5 sec. The frictional coefficient increased with the length of the preceding loading duration and exceeded 0.0220 (SD 0.0014) after 1 hr. Application of larger loading (80 N) resulted in significantly larger frictional coefficients. In conclusion, the frictional coefficient in the TMJ was proportional to the magnitude and duration of joint loading.

Algorithms↗

PubMed2004

Shear properties of the temporomandibular joint disc in relation to compressive and shear strain.

Shear stress can result in fatigue, damage, and irreversible deformation of the temporomandibular joint disc. Insight into the dynamic shear properties of the disc may give insight into the mechanism inducing tissue failure due to shear. We tested the hypothesis that the dynamic shear properties of the disc depend on the amount of shear and compressive strain. Twenty-four porcine discs were used for dynamic shear tests. The specimens were clamped between the plates of a loading apparatus under compressive strains of 5%, 10%, and 15%. Dynamic shear was applied to the specimen by a sinusoidal strain of, respectively, 0.5%, 1.0%, and 1.5%. Both the dynamic elasticity and viscosity were proportional to compressive strain and inversely proportional to shear strain. These shear characteristics suggest a significant role of compressive and shear strain on the internal friction of the disc.

Algorithms↗

PubMed2004

Prolactin gene expression in mouse spleen helper T cells.

Prolactin (PRL) is a single-chain polypeptide hormone that is generally secreted from prolactin cells of the anterior pituitary gland into the blood circulation. However, recent studies indicate that the gene expression of prolactin is ectopic in several tissues across several species. These studies found that lymphocytes also produce PRL, which is involved in the immunoregulatory system. Here, we searched for PRL messenger ribonucleic acid (mRNA), using the reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting in the spleens of mice at various growth stages. We also localized mouse prolactin (mPRL) and its mRNA in the spleens of 30- and 60-day-old mice by immunohistochemistry and in situ hybridization respectively. The mPRL gene was expressed in all spleen samples at 0-60 days postpartum. We localized mPRL mRNA in the sheathed artery, periarterial lymphatic sheath and the marginal zone of the spleen. Moreover, we detected mPRL in essentially the same area as its mRNA. Furthermore, we performed double-fluorescence immunohistochemical staining for mPRL and mouse CD4 that is specifically produced in helper T cells, or for mPRL and mouse CD19 or CD40 specified B cells. We colocalized mPRL immunoreactivity only in some CD4-immunopositive cells. These results clearly suggest that T cells synthesize mPRL in the mouse spleen.

Animals↗

PubMed2004

Characterization of junctional sarcoplasmic reticulum Ca2+ content and release by short-term mechanical restitution in cardiac muscle.

To study Ca2+ handling by the junctional sarcoplasmic reticulum (JSR), the time course of short-term mechanical restitution after varying magnitudes of twitch contractions was assessed in rat papillary muscle. Mechanical restitution consisted of a pretwitch latency period followed by a rapid and a subsequent much slower restitution of twitch force. The rate of rapid restitution was independent of the magnitude of the preceding twitch, which suggests that the rate of JSR Ca2+ repletion was dependent on the amount of Ca2+ remaining in the JSR after a twitch contraction. Based on this finding, the functions Gt and Ht, representing the time courses of JSR Ca2+ repletion and release, respectively, were derived graphically from a family of the mechanical restitution curves. Gt increased monotonically with time at a decreasing rate, while Ht increased with time in a sigmoid manner. The mechanical alternans were simulated by using experimental values and mathematically predicted values of Gt and Ht. A substitution of extracellular Na+ with Li+ to inhibit Na+/Ca2+ exchange resulted in an augmentation of Gt by approximately 10%, presumably by increasing the tubular SR Ca2+ uptake. The inhibition of tubular SR Ca2+ uptake by thapsigargin (10 microM) reduced mechanical restitution by approximately 13% of the maximal twitch force, independent of the phase of mechanical restitution; the effect was greater at an earlier time point in the mechanical restitution. These results suggest that early JSR Ca2+ replenishment results mainly from the movement of Ca2+ from the tubular SR.

Adaptation, Physiological↗

PubMed2004

Reduced low-density-lipoprotein cholesterol causing low serum cholesterol levels in gastrointestinal cancer: a case control study.

Several epidemiological studies suggested an inverse relation between serum cholesterol level and cancer mortality. We analyzed the relation between gastrointestinal cancers and serum cholesterol levels. A total of 631 patients were recruited as cancer-bearing cases, comprising 181 esophageal cancers, 251 gastric cancers and 199 colorectal cancers. A case-control analysis was conducted on the serum TC, HDL-C, LDL-C and TG levels. TC and LDL-C were significantly lower in cancer-bearers by approximately 15 mg/dl. Furthermore, analyses by cancer site also showed significantly lower TC and LDL-C levels in cancer-bearers than in controls for all three sites. In this analysis, early stage cancer-bearers showed a significant decrease in TC levels by approximately 11 mg/dl compared with controls, and also a similar decrease in LDL-C levels. These results suggest that low TC levels are not related to cancer stage. Furthermore, findings of no significant differences in HDL-C and TG between cancer-bearing cases and controls in addition to a specific decrease in LDL-C in cancer-bearers suggest that hypocholesterolemia observed in these cases stems from low LDL-C. However, cancer-bearers and controls showed a similar distribution of TC and LDL-C levels. We should be aware that latent cancer bearers may be present among subjects with hypocholesterolemia.

Case-Control Studies↗

PubMed2003

Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Mechanical stress, which acts on the posterior ligaments, is thought to be an important factor in the progression of OPLL. To clarify this mechanism, we investigated the effects of in vitro cyclic stretch (120% peak to peak, at 0.5 Hz) on cultured spinal ligament cells derived from OPLL (OPLL cells) and non-OPLL (non-OPLL cells) patients. The mRNA expressions of Cbfa1 (an osteoblast-specific transcription factor), type I collagen, alkaline phosphatase (ALP), osteocalcin and integrin beta1 (a mechanotransducer) were increased by cyclic stretch in OPLL cells, whereas no change was observed in non-OPLL cells. The effects of cyclic stretch on the spinal ligament tissues derived from OPLL and non-OPLL patients were also analyzed by immunohistochemistry using an antibody against Cbfa1. The expression of Cbfa1 was increased by cyclic stretch at the center of the spinal ligament tissues of OPLL patients, whereas no change was observed in the tissues of non-OPLL patients. Furthermore, U0126, a specific inhibitor of MAPK kinase (MEK), suppressed the stretch-induced mRNA expressions of Cbfa1, ALP and type I collagen in OPLL cells. These results suggest that in OPLL cells, mechanical stress is converted by integrin beta1 into intracellular signaling and that Cbfa1 is activated through the MAP kinase pathway. Therefore, we propose that mechanical stress plays a key role in the progression of OPLL through an increase in Cbfa1 expression.

Aged↗

PubMed2003

Phase I clinical study of a novel lipophilic platinum complex (SM-11355) in patients with hepatocellular carcinoma refractory to cisplatin/lipiodol.

SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC). It is administered via the hepatic artery, using a carrier, lipiodol, that consists of ethyl esters of iodized poppy seed oil. We have performed a phase I clinical trial of an SM-11355-lipiodol formulation in 11 HCC patients, in order to investigate the maximum allowable dose and to maximize the efficacy and safety of the drug in the treatment of HCC. The SM-11355 arterial infusion suspension was administered at doses of 6, 12 and 20 mg ml(-1) in a maximum lipiodol volume of 6 ml. An antitumour efficacy rating of complete response was achieved for one patient and a partial response rating was achieved for a second patient, giving an overall response rate of 18.2%. Anorexia, nausea and vomiting, pyrexia, thrombocytopenia and increases in AST, ALT and total bilirubin were observed as adverse effects, but each was transient and each patient had recovered completely by 4 weeks after drug administration. Hence, we concluded that the maximum allowable dose was not reached in this study. Overall, our results suggest that SM-11355 is effective in treating HCC and we suggest that the dose for early phase II trials should be 20 mg ml(-1).

Adult↗

PubMed2003

Assessment of cytochrome P450 sequences offers a useful tool for determining genetic diversity in higher plant species.

To investigate and develop new genetic tools for assessing genome-wide diversity in higher plant-species, polymorphisms of gene analogues of mammalian cytochrome P450 mono-oxygenases were studied. Data mining on Arabidopsis thaliana indicated that a small number of primer-sets derived from P450 genes could provide universal tools for the assessment of genome-wide genetic diversity in diverse plant species that do not have relevant genetic markers, or for which, there is no prior inheritance knowledge of inheritance traits. Results from PCR amplification of 51 plant species from 28 taxonomic families using P450 gene-primer sets suggested that there were at least several mammalian P450 gene mammalian-analogues in plants. Intra- and inter- specific variations were demonstrated following PCR amplifications of P450 analogue fragments, and this suggested that these would be effective genetic markers for the assessment of genetic diversity in plants. In addition, BLAST search analysis revealed that these amplified fragments possessed homologies to other genes and proteins in different plant varieties. We conclude that the sequence diversity of P450 gene-analogues in different plant species reflects the diversity of functional regions in the plant genome and is therefore an effective tool in functional genomic studies of plants.

Arabidopsis↗

PubMed2003

Prevention of advanced colorectal cancer by screening using the immunochemical faecal occult blood test: a case-control study.

To evaluate colorectal cancer screening with faecal occult blood testing (FOBT) in terms of prevention of advanced cancers, we conducted a case-control study in the areas where an annual screening programme with immunochemical FOBT has been offered to all inhabitants aged 40 years or over. Cases were 357 consecutive patients in the study areas clinically diagnosed as having advanced colorectal cancer or a tumour invading the muscularis propriae or deeper, that is, T(2)-T(4) in TNM classification. Three controls were selected for each case matched by gender, age, residential area and exposure status to screening within 1 year before case diagnosis. The odds ratios (ORs) of developing advanced cancer were calculated using conditional logistic regression analyses. The OR for those screened within 3 years before the diagnosis vs those not screened was 0.54 (95% confidence interval (CI) 0.29-0.99). The ORs were lower for rectum than for colon (0.32-0.73 and 0.84-1.18 for rectum and colon, respectively). For those screened within the past 3 years, OR of developing advanced cancer in the rectum was 0.32 ( 95%CI: 0.12-0.84). A screening programme with immunochemical FOBT can be effective for prevention of advanced colorectal cancer. Risk reduction appears to be larger for rectal than for colon cancer. British Journal of Cancer (2003) 89, 23-28. doi:10.1038/sj.bjc.6601002 www.bjcancer.com

Adult↗

PubMed2003

Oncostatin M, a multifunctional cytokine.

Oncostatin M (OSM) is a multifunctional cytokine that belongs to the Interleukin (IL)-6 subfamily. Among the family members, OSM is most closely related to leukemia inhibitory factor (LIF) and it in fact utilizes the LIF receptor in addition to its specific receptor in the human. While OSM was originally recognized by its unique activity to inhibit the proliferation of tumor cells, accumulating evidence now indicates that OSM exhibits many unique biological activities in inflammation, hematopoiesis, and development. Here, we review the profile of OSM activities, receptors, and signal transduction.

Animals↗

PubMed2003

A gene for a Class II DNA photolyase from Oryza sativa: cloning of the cDNA by dilution-amplification.

Ultraviolet radiation induces the formation of two classes of photoproducts in DNA-the cyclobutane pyrimidine dimer (CPD) and the pyrimidine [6-4] pyrimidone photoproduct (6-4 product). Many organisms produce enzymes, termed photolyases, which specifically bind to these lesions and split them via a UV-A/blue light-dependent mechanism, thereby reversing the damage. These photolyases are specific for either CPDs or 6-4 products. Two classes of photolyases (class I and class II) repair CPDs. A gene that encodes a protein with class II CPD photolyase activity in vitro has been cloned from several plants including Arabidopsis thaliana, Cucumis sativus and Chlamydomonas reinhardtii. We report here the isolation of a homolog of this gene from rice (Oryza sativa), which was cloned on the basis of sequence similarity and PCR-based dilution-amplification. The cDNA comprises a very GC-rich (75%) 5; region, while the 3; portion has a GC content of 50%. This gene encodes a protein with CPD photolyase activity when expressed in E. coli. The CPD photolyase gene encodes at least two types of mRNA, formed by alternative splicing of exon 5. One of the mRNAs encodes an ORF for 506 amino acid residues, while the other is predicted to code for 364 amino acid residues. The two RNAs occur in about equal amounts in O. sativa cells.

Amino Acid Sequence↗

PubMed2003

Gallbladder duplication successfully removed laparoscopically using endoscopic nasobiliary tube.

Laparoscopic cholecystectomy is sometimes difficult due to complicated biliary anatomy including gallbladder duplication, a rare anomaly of the biliary tract. We report a case of duplicated gallbladder successfully removed under laparoscopy using endoscopic nasobiliary (ENB) tube cholangiography. A 61-year-old Japanese woman presented us with right upper abdominal pain. Ultrasonography revealed two cystic structures lying in the gallbladder fossa, and the upper one contained multiple stones. Endoscopic retrograde cholangiography showed two gallbladders, each of which has a cystic duct draining into the common bile duct separately. Laparoscopic cholecystectomy was planned under the preoperative diagnosis of double gallbladder with gallstones in the accessory gallbladder. The ENB tube was inserted just before the operation. Laparoscopic removal of the double gallbladder was successfully done using the ENB tube to identify the biliary tree anatomy and to close the stump of the cystic duct. In this communication, we would like to stress the usefulness of the ENB tube at the time of laparoscopic biliary surgery in patients with biliary anomalies including gallbladder duplication.

Bile Ducts↗

PubMed2003

Combined evaluation of mucin antigen and E-cadherin expression may help select patients with gastric cancer suitable for minimally invasive therapy.

BACKGROUND: MUC1 mucin is known to be highly expressed in carcinomas that show invasive growth and poor prognosis. Impairment of adhesion molecule E-cadherin expression has been widely accepted as a critical event for cancer invasion and metastasis. The present study evaluated the combination of mucin and E-cadherin status as a possible predictor of patients suitable for minimally invasive therapy for gastric cancer. METHODS: Two hundred and nine paraffin-embedded specimens of gastric carcinoma (141 early, 68 advanced) were examined by immunohistochemical staining using monoclonal antibodies against MUC1 mucin (MUC-1-CORE, DF3), MUC2 mucin (Ccp58) and E-cadherin (anti-E-cad). RESULTS: Gastric carcinoma with MUC1-positive expression demonstrated malignant characteristics. Normal E-cadherin expression showed an inverse correlation with MUC1 expression. Patients with early gastric carcinoma who had a combination of normal E-cadherin and MUC1-negative expression had no recurrence and a favourable prognosis. Moreover, cancers with normal E-cadherin/MUC1-negative expression were not found at an advanced stage in differentiated-type carcinoma. CONCLUSION: A normal E-cadherin/MUC1-negative expression pattern in gastric cancer is a favourable marker. Preoperative estimation of the E-cadherin and MUC1 status of an endoscopic biopsy specimen may help select appropriate patients for minimally invasive treatment of gastric cancer.

Antibodies, Monoclonal↗

PubMed2003

Cell cycle aberrations by alpha-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies.

alpha-Synuclein is a presynaptic protein that accumulates abnormally in Lewy bodies of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Its physiological function and role in neuronal death remain poorly understood. Recent immunohistochemical studies suggest that cell cycle-related phenomena may play a role in the pathogenesis of Alzheimer's disease and perhaps other neurodegenerative disorders. In this investigation, we examined the effects of alpha-synuclein expression levels on cell cycle indices in PC12 cells engineered to conditionally induce alpha-synuclein expression upon withdrawal of doxycycline. Over-expression of alpha-synuclein resulted in enhanced proliferation rate and enrichment of cells in the S phase of the cell cycle. This was associated with increased accumulation of the mitotic factor cyclin B and down-regulation of the tumor suppressor retinoblastoma 2. Additionally, ERK1/2, key molecules in proliferation signaling, were highly phosphorylated. Immunohistochemical studies on postmortem brains revealed intense cyclin B immunoreactivity in Lewy bodies in cases with DLB and to a lesser extent in PD. We propose that elevated expression of alpha-synuclein causes changes in cell cycle regulators through ERK activation leading to apoptosis of postmitotic neurons. These changes in cell cycle proteins are also associated with ectopic expression of cyclin B in Lewy bodies.

Animals↗