Biomedical subjects

S Morita

Publications and source records attributed to S Morita.

At least 19 recordsLinked to original sources

PubMed2026

Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.

BACKGROUND: The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. PATIENTS AND METHODS: Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). RESULTS: Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. CONCLUSION: Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.

Aged↗

PubMed2006

Preparation of prefabricated vascularized bone graft with neoangiogenesis by combination of autologous tissue and biodegradable materials.

Prefabricated vascularized bone grafts have previously been prepared by combining an autologous vessel bundle with auto-particulate cancellous bone and marrow (PCBM) and a biodegradable membrane. Only small quantities of low-density vascularized bone tissue have been formed using this method. The authors of the present study combined beta-tricalcium phosphate (beta-TCP), a biodegradable ceramic, with a prefabricated vascularized bone graft to augment osteogenesis. A saphenous vessel bundle from a rat was wrapped in a biodegradable membrane. Then, autologous PCBM was mixed with beta-TCP granules and packed into the rolled membrane. In the control group, beta-TCP was omitted. Bone formation was histologically assessed 6 and 9 weeks after implantation. The volume of newly formed bone tissue in the rolled membrane was greater in the presence of beta-TCP granules than in the control. Microvessels had formed throughout the new bone tissue. When a prefabricated vascularized bone graft was onlay-grafted to the femur of the same rat, the prefabricated vascularized bone graft directly fused to the cortical surface of the femur, with no intervening fibrous tissue. These findings suggest that beta-TCP in combination with PCBM enhances the volume and density of bone tissue in prefabricated vascularized bone grafts.

Absorbable Implants↗

PubMed2006

Genome-wide profiling of promoter methylation in human.

DNA methylation in the promoter region of a gene is associated with a loss of that gene's expression and plays an important role in gene silencing. The inactivation of tumor-suppressor genes by aberrant methylation in the promoter region is well recognized in carcinogenesis. However, there has been little study in this area when it comes to genome-wide profiling of the promoter methylation. Here, we developed a genome-wide profiling method called Microarray-based Integrated Analysis of Methylation by Isoschizomers to analyse the DNA methylation of promoter regions of 8091 human genes. With this method, resistance to both the methylation-sensitive restriction enzyme HpaII and the methylation-insensitive isoschizomer MspI was compared between samples by using a microarray with promoter regions of the 8091 genes. The reliability of the difference in HpaII resistance was judged using the difference in MspI resistance. We demonstrated the utility of this method by finding epigenetic mutations in cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes. Using this method, we found that frequency of the aberrant promoter hypermethylation in cancer is higher than previously hypothesized. Aberrant hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC ratio of these sequences, suggesting that CpG-poor genes are sensitive to demethylation activity in cancer.

Adenocarcinoma↗

PubMed2006

NFkappaB decoy oligodeoxynucleotides ameliorates osteoporosis through inhibition of activation and differentiation of osteoclasts.

The transcription factor, nuclear factor-kappa B (NFkappaB), is believed to play a pivotal role in osteoclast formation. In this study, we focused on NFkappaB decoy oligodeoxynucleotides (ODN) as a new therapeutic strategy to attenuate osteoporosis. Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts formed in mononuclear cells including osteoclast precursors from neonatal rabbit bone marrow were increased in the presence of 1,25-dihydroxyvitamin D3, whereas transfection of NFkappaB decoy ODN decreased the number of TRAP-positive cells and attenuated RANKL and M-CSF-induced osteoclast formation. NFkappaB decoy ODN also inhibited the activity of osteoclasts, as assessed by pit formation. In rat ovariectomized model of estrogen deficiency, continuous administration of NFkappaB decoy ODN attenuated the increase of TRAP activity, accompanied by a significant increase in calcium concentration in tibia and femur and decrease in urinary deoxypyridinoline. In additional osteoporosis model using vitamin C-deficient rat, inhibition of NFkappaB by decoy ODN dramatically improved the bone length, weight, density as assessed by dual-energy X-ray absorptiometry. Overall, inhibition of NFkappaB by decoy strategy prevented osteoporosis through the inhibition of bone resorption. Targeting of NFkappaB might be potential therapy in various bone metabolic diseases.

Absorptiometry, Photon↗

PubMed2006

Genomic imprinting in Dicer1-hypomorphic mice.

To address the function of RNA interference (RNAi) in transcriptional silencing in mammals, we analyzed genomic imprinting in Dicer1-hypomorphic mice, in which Dicer1 expression was significantly reduced. We did not observe any abnormality in the allelic expression of imprinted genes in these mice or their offspring, suggesting that reduced expression of Dicer1 did not significantly affect the maintenance and reprogramming of imprinting.

Animals↗

PubMed2006

Efficacy of adjuvant chemotherapy using oral fluorinated pyrimidines for curatively resected gastric cancer: a meta-analysis of centrally randomized controlled clinical trials in Japan.

Adjuvant chemotherapy for gastric cancer has been extensively explored in Japan since the 1950s, and a combination of oral fluorinated pyrimidines (o-FP) and mitomycin C (MMC) has been mainly utilized for adjuvant chemotherapy. However, there is no sufficient evidence for the efficacy of adjuvant therapy. Therefore, we assessed the efficacy of o-FPs over surgery alone (control) by means of a meta-analysis of Japanese centrally randomized controlled clinical trials conducted between 1980 and 2005. For inclusion in this study, studies had to compare adjuvant chemotherapy for curatively resected gastric cancer with surgery alone, mainly targeting o-FP, and central randomization designed to comply with contemporary standards for clinical trials in Japan. For the 4 trials that met the eligibility criteria, the estimated hazard ratio was 0.73 (95%CI=0.60-0.89). Our findings show that in Japan adjuvant chemotherapy using o-FP for long-term maintenance therapy appears to be effective for gastric cancer patients after curative resection.

Antibiotics, Antineoplastic↗

PubMed2005

Direct observation of a (3 x 3) phase in alpha-Pb/Ge(111) at 10 K.

We have investigated the recently reported structural phase transition at low temperature (LT) for alpha-Pb/Ge(111) [from a (3 x 3) symmetry to a disordered phase] using scanning tunneling microscopy (STM). By tracking exactly the same surface regions with atomic resolution while varying the sample temperature from 40 to 140 K, we have observed that substitutional point defects are not mobile, in clear contrast to previous assumptions. Moreover, STM data measured at the lowest temperatures ever reported for this system (10 K) show that while filled-state images display the apparent signature of a glassy phase with no long-range order, in empty-state images honeycomb patterns with (3 x 3) periodicity, and not distinguishable from data measured at much higher temperatures, are clearly resolved. These new observations cast serious doubts on the nature and/or on the existence of a disordered phase at LT.

Journal Article↗

PubMed2005

Inhibition of inflammatory cytokine secretion from mouse microglia cells by DHMEQ, an NF-kappaB inhibitor.

Activation of microglia has been implicated in various neurodegenerative disorders, and thus the inhibition of microglial activity may suppress these disorders. Earlier we designed and synthesized an NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) that showed anti-inflammatory and anti-tumor activities in vivo. In the present research, we studied whether DHMEQ would inhibit the activation of mouse microglial cells. DHMEQ inhibited lipopolysaccharide (LPS)-induced activation of NF-kappaB in an electrophoresis mobility shift assay. It also inhibited LPS-induced secretions of TNF-alpha and IL-6 from mouse microglial cell line 6-1 cells.

Animals↗

PubMed2005

Endoscopic and histologic evaluation of advanced megaesophagus after esophagocardioplasty, vagotomy-antrectomy and roux-en-Y gastrojejunostomy (Serra Dória operation).

To evaluate the endoscopic and histologic aspects of the esophageal mucosa in patients who underwent the Serra Dória operation for advanced megaesophagus. Thirty patients with advanced megaesophagus underwent the Serra Dória operation (operated group) and 15 patients were not submitted to surgery (non-operated group). The esophageal mucosa was evaluated by macroscopy and histologic examinations. In the operated group, 21, five and four patients with mild, moderate and severe esophagitis, respectively, were identified by endoscopy. In the non-operated group, 4 and 11 patients had moderate and severe esophagitis, respectively. The histologic examinations identified 19, six and five specimens with mild, moderate and severe esophagitis, respectively, in the operated group as opposed to one, three and 11 specimens with mild, moderate and severe esophagitis, respectively, in the non-operated group. The prevalence of severe esophagitis was high in the non-operated group while, after the Serra Dória operation, mild esophagitis was prevalent.

Adult↗

PubMed2005

Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma.

BACKGROUND: The balance between matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP-1 over MMP-9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic (CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction. METHODS: Sputum levels of MMP-9, TIMP-1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area (WA/BSA), the ratio of WA to outer wall area (WA%), and the absolute wall thickness corrected by radicalBSA of a segmental bronchus (T/ radicalBSA), was examined. RESULTS: Sputum MMP-9 levels were inversely correlated with WA% and TIMP-1 levels were positively correlated with WA/BSA and T/ radicalBSA. The MMP-9/TIMP-1 molar ratio was inversely correlated with WA% and T/ radicalBSA and positively correlated with post-bronchodilator values of mid-forced expiratory flow and maximum expiratory flow at the quartile of lung volume. CONCLUSION: Excess TIMP-1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.

Asthma↗

PubMed2004

Cardiovascular effects of xenon and nitrous oxide in patients during fentanyl-midazolam anaesthesia.

Xenon anaesthesia appears to have minimal haemodynamic effects. The purpose of this randomised prospective study was to compare the cardiovascular effects of xenon and nitrous oxide in patients with known ischaemic heart disease. In 20 patients who were due to undergo coronary artery bypass graft surgery, 30 min following induction of anaesthesia with fentanyl 30 microg x kg(-1) and midazolam 0.1 mg x kg(-1) but prior to the start of surgery, xenon or nitrous oxide 60% was administered for 15 min. The results showed that xenon caused a minimal decrease in the mean arterial pressure (from 81 (7) to 75 (8) mmHg, mean (SD)), but did not affect the systolic function of the left ventricle, as demonstrated by unchanged left ventricular stroke work index (LVSWI) and the fractional area change of the left ventricle (FAC) derived from transoesophageal echocardiography (TOE). However, in contrast, nitrous oxide was found to decrease the mean arterial pressure (from 81 (8) to 69 (7) mmHg), the LVSWI, and the FAC. The cardiac index, central venous and pulmonary artery occlusion pressures, systemic and pulmonary vascular resistances, and the TOE-derived E/A ratio through the mitral valve were unchanged by xenon or nitrous oxide. We conclude that xenon provides improved haemodynamic stability compared with nitrous oxide, conserving the left ventricular systolic function.

Aged↗

PubMed2004

Beliefs of chronically ill Japanese patients that lead to intentional non-adherence to medication.

OBJECTIVE: To identify factors, associated with personal beliefs, involved in intentional non-adherence to prescribed medication of Japanese patients with chronic diseases. METHODS: A cross-sectional study of Japanese subjects with chronic, primarily liver, gastrointestinal, or nervous system diseases who had been prescribed oral medicines for regular use, was performed. The subjects were admitted to a university hospital and were interviewed face-to-face on admission. Intentional non-adherence was defined as experience of deliberate adjustment of self-managed prescription medicines during the few months prior to hospital admission. Patients' beliefs about taking medicines were assessed from the perspective of what the patient valued in order to take medicines without anxiety; whether the patient valued information about the medication such as its function and side-effects and/or mutual reliance on doctors. Using logistic multivariate regression analyses, factors associated with intentional non-adherence were identified. RESULTS: Among 154 subjects, 51 showed intentional non-adherence. Intentional non-adherence was associated with the following three factors: (a) the patients' beliefs with respect to taking medicines without anxiety, especially putting no value on mutual reliance on the patient-doctor relationship (P < 0.001) and putting great value on knowing the drug's side-effects (P < 0.001), (b) poor comprehension of general aspects of medication (P for trend < 0.001), and (c) being in the prime of life (40-59 years) (P = 0.011). Comprehension of the function of each medicine, experience of side-effects, anxiety about taking medicines, and the number of types of medicines taken, were not associated with non-adherence. CONCLUSIONS: Beliefs on which individual Japanese patients with chronic diseases attach value in order to take medicines without anxiety were potential factors for intentional non-adherence. This emphasizes the necessity of a patient-oriented approach to take account of patients' personal beliefs about medicines to increase adherence rate in Japan.

Administration, Oral↗

PubMed2004

The natural history of maternal immunization against foetal platelet alloantigens.

Foetomaternal alloimmune thrombocytopenia (FMAIT) occurs when maternal antibodies of an antigen-negative mother cause destruction of sensitized foetal platelets. In Caucasian populations, 6-12% of human platelet antigen (HPA)-1a-negative women develop anti-HPA-1a, and the incidence of clinically affected cases is estimated to be 10-20% of immunized women. This study was performed in order to elucidate the rate of maternal immunization, incidence of FMAIT and the likely outcome of the condition in Asians. Excluding two or more pregnancies during the period, serum samples from 24 630 pregnant women, mainly Japanese, were screened for antibodies against platelet alloantigens by means of mixed passive haemagglutination (MPHA) (Anti-HPA-MPHA, Olympus, Tokyo). Antibodies were detected in 0.91% (223/24 630) of the women's samples and the immunization rate was correlated with the number of pregnancies. Antibody specificity included anti-HPA-4b (49), anti-HPA-5a (three), anti-HPA-5b (168), anti-HPA-4b + 5b (one) and anti-Nak(a) (CD36) (two). No alloimmunization was observed within the HPA-1, HPA-2, HPA-3 or HPA-6 systems. Among HPA-4b- or HPA-5b-negative women, 24% or 14% estimated, respectively, had antibodies and 26% (10/38) or 10% (12/125) of neonates, respectively, born to these mothers developed thrombocytopenia. Two neonates born to mothers having anti-HPA-4b developed generalized purpura. No cases of intracranial bleeding or death due to FMAIT were recorded. Generalized purpura due to FMAIT occurs in one in 9359 (95% CI: 1 in 77 519-1 in 2591) pregnancies solely because of HPA-4b incompatibility.

Antigens, Human Platelet↗

PubMed2004

Neonatal alloimmune thrombocytopenia due to an antibody against a labile component of human platelet antigen-3b (Bak b).

We report the second case of neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-3b (Bak(b)) antibody. The infant was severely affected with intracranial haemorrhage. Most importantly, we were able to detect this antibody only by using fresh, unfixed platelets as antigen. This antibody was detectable neither by conventional mixed passive haemagglutination, platelet immunofluorescence test using fixed platelets, nor by monoclonal antigen immobilization of platelet antigen assay using solubilized platelets. We assume that this antibody reacts only with fresh platelets and that the antigen is a labile component of HPA-3b (Bak(b)).

Antigens, Human Platelet↗

PubMed2004

Parathyroid invasion, nodal recurrence, and lung metastasis by papillary carcinoma of the thyroid.

AIMS: Parathyroid invasion by papillary thyroid carcinoma (PTC) is found in a small proportion of surgical specimens, but the clinicopathological relevance of this phenomenon is not well understood. This study investigated the possible prognostic relevance of parathyroid invasion in PTC. METHOD: Parathyroid involvement was seen in 14 patients with PTC, and the clinicopathological characteristics and follow up data of these patients were analysed and compared with 164 patients without parathyroid involvement, in whom histological parathyroid examination had been undertaken, and 177 other patients without parathyroid examination (341 patients without parathyroid involvement in total). RESULTS: Parathyroid invasion was found in older patients and there were more male patients in this group than in those without parathyroid invasion. These patients had more extrathyroid extension and were frequently in an advanced stage of disease. Lung metastasis was seen in two of the 14 patients, which was significantly more than that seen in control cases. Moreover, male patients with parathyroid invasion and those who were older than 55 years had reduced disease free survival compared with those without parathyroid invasion. CONCLUSION: Parathyroid invasion seen in thyroid carcinoma may be an important histological feature indicating a greater chance of nodal recurrence and lung metastasis.

Age Factors↗

PubMed2004

Physicians' choice in using Internet and fax for patient recruitment and follow-up in a randomized controlled trial.

OBJECTIVE: To examine the physicians' preference between Web and fax-based remote data entry (RDE) system for an ongoing randomized controlled trial (RCT) in Japan. METHODS: We conducted a survey among all the collaborating physicians (n = 512) of the CASE-J (Candesartan Antihypertensive Survival Evaluation in Japan) trial, who have been recruiting patients and sending follow-up data using the Web or a fax-based RDE system. The survey instrument assessed physicians' choice between Web and fax-based RDE systems, their practice pattern, and attitudes towards these two modalities. RESULTS: A total of 448 (87.5%) responses were received. The proportions of physicians who used Web, fax, and the combination of these two were 45.9%, 33.3% and 20.8%, respectively. Multivariate logistic regression analyses revealed that physicians 55 years or younger [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.3] and regular users of computers (OR = 4.2, 95% CI = 2.1-8.2) were more likely to use the Web-based RDE system. CONCLUSIONS: This information would be useful in designing an RCT with a Web-based RDE system in Japan and abroad.

Adult↗

PubMed2004

Thirty cases of bronchial asthma associated with exposure to pet hamsters.

BACKGROUND: The identification, isolation, and elimination of allergen(s) causing bronchial asthma are the most efficient form of treatment. The pet industry has diversified recently, increasing the risk of exposure of pet owners to many unknown antigens. We clinically studied the characteristics of asthma associated with exposure to pet hamsters. METHODS: The study group comprised 30 adults in whom the onset, recurrence, or exacerbation of asthma was triggered by contact with pet hamsters. Clinical characteristics such as sex, age, period required for symptom onset, species of hamster, treatment and disease course, smoking status, and hamster-specific IgE antibodies in serum were studied. RESULTS: The male: female ratio of the study group was 1:1.3, and mean age was 37.7 years. Patients with no previous history of asthma initially presented with cough, progressing to episodes of asthma. Asthmatic symptoms were associated with hamster contact and ranged in severity from mild to severe. Three patients required hospital admission for treatment. The mean period from the start of hamster exposure to the onset of asthmatic episodes was 15.7 months. Dwarf hamsters were responsible for most cases. The CAP-RAST score for hamster-specific IgE antibodies was 1 to 4 in 22 patients and 0 in 8 patients. Eight patients with a score of 1 or higher for hamster-specific IgE antibodies had a CAP-RAST score of 0 for mite antigen. In these patients, terminating hamster contact resulted in a rapid improvement in symptoms, with no need for further treatment. Twenty-three of the 30 subjects (76.7%) were smokers. CONCLUSION: Exposure to pet hamsters is an important risk factor for the onset, recurrence, or exacerbation of asthma. Smoking may also increase the risk of asthmatic symptoms in patients exposed to hamsters.

Adult↗

PubMed2004

Clinical evaluation of response to long-term treatment with Pranlukast in patients with bronchial asthma.

BACKGROUND: Short-term treatment with pranlukast, a leukotriene receptor antagonist, has shown to be effective for the management of asthma. The effectiveness and safety of long-term treatment with pranlukast remains to be established. OBJECTIVES: The aim of this study was to determine the effects of pranlukast on morning peak expiratory flow rates (PEFRs), the diurnal variation of these values, and disease severity. METHODS: Fifteen men with bronchial asthma were studied for 5 years. During the first year, the subjects were treated with a bronchodilator; some also received inhaled and oral corticosteroids. During the next 4 years, the subjects received pranlukast in addition. RESULTS: Mean PEFR increased after the start of treatment with pranlukast. The increase in PEFR occurred later in subjects with more severe disease. Diurnal variation of PEFR was unchanged, but subsequently decreased. The condition of all subjects improved, but the greatest improvement was obtained in patients with mild to moderate asthma. CONCLUSIONS: Long-term treatment with pranlukast is effective for the management of bronchial asthma, particularly in patients with mild to moderate disease. Our results suggest that the effectiveness of antiasthmatic drugs should be evaluated over a period of years, rather than on a short-term basis.

Adrenal Cortex Hormones↗