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Biomedical subjects

T Morimoto

Publications and source records attributed to T Morimoto.

13 recordsLinked to original sources

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

In vitro synthesis of the Ca2+ transport ATPase by ribosomes bound to sarcoplasmic reticulum membranes.

The calcium transport ATPase (M(r) 100,000) from sarcoplasmic reticulum membranes was synthesized in a cell-free translation system containing rough microsomes or detergent-treated bound polysomes from 14- to 16-day old chicken embryo muscles. Immunoprecipitates obtained from total translation mixtures treated with anti-ATPase antiserum contained 1.5% of the total radioactivity incorporated in vitro. A polypeptide with the electrophoretic mobility, isoelectric point, and [(35)S]methionine-labeled tryptic peptide pattern of the mature ATPase was a major component of these immunoprecipitates. By contrast, free polysomes from the same source, which were capable of high levels of in vitro protein synthesis, did not yield immunoprecipitable ATPase. ATPase synthesized in rough microsomes was not released by treatment with 10 mM EDTA in a high-salt medium (0.5 M KCl) which removes ribosomes and peripheral membrane proteins. Furthermore, labeled ATPase remained associated with the microsomes after these were treated with low concentrations of deoxycholate (0.1 mg/mg of protein in 0.3 ml) which release the luminal content of the vesicles. Only with higher deoxycholate concentrations (0.5 mg/mg of protein in 0.3 ml), which cause membrane dissolution, was the labeled ATPase found on the detergent extracts. These observations indicate that newly synthesized ATPase discharged from bound ribosomes is transferred directly to the sarcoplasmic reticulum membranes where it is incorporated as an integral membrane protein.

Animals

Effects of the interpolated vibratory stimulation on the interdental dimension discrimination in normal and joint defect subjects.

No significant differences in the interdental dimension discrimination (IDD) ability were found between normal and joint defect subjects. Furthermore, vibration onto the mandible gave similar effects on the nature of IDD in both subject groups. Thus, the muscle spindles of masticatory muscles may contribute to IDD, but temporomandibular receptors may not.

Adolescent

Intracellular pH measurement in frog muscle by means of 31P-nuclear magnetic resonance.

The 31P-NMR technique was used for the monitoring of intracellular pH and studying its heterogeneity in the femoral biceps muscle of Rana catesbiana under anaerobic conditions. The value of intracellular pH of fresh muscle calculated from the chemical shift of intracellular inorganic phosphate (P1) was 7.3 on average and the line width of P1 was about 0.2 ppm. As the line width determined by the relaxation mechanism was 0.099 ppm, the P1 signal in fresh muscle was concluded to consist of overlapped narrow components, which indicated the heterogeneity of muscular pH (about 0.2 pH unit). Living muscle showed gradual acidification due to glycolysis and the decrease in heterogeneity. When glycolysis was suppressed by iodoacetic acid, slight alkalization due to the breakdown of creatine phosphate was observed. When the Lohmann reaction was suppressed by 2, 4-dinitro-1-fluorobenzene, rapid acidification accompanied by the appearance of a new acidic component was observed with the onset of ATP decrease. This new component was not detected in the muscle pretreated with glycerol to disrupt the transverse tubules. Therefore, it is likely that this new acidic component originates in the intracellular compartment, and not in the cellular difference.

Animals

Long-term changes in the perception of comfortable mandibular occlusal positions.

The aim of this study was to disclose, whether use of a screw jack device to set the distance between the jaws, would contribute towards a stabilization of the magnitude and position of a comfortable zone of mandibular positions or even eliminate it. Thirteen subjects participated in each of fifteen experimental sessions distributed over a 3-week period. Throughout the investigation the zone prevailed at an average width of 1-3 mm. The gap shrank 0-08 mm on average per experimental session. Although this latter value was found to be significant statistically, it can hardly be of clinical importance, considering the time needed for a total contraction of 0-8 mm to develop.

Aged

Dimension discrimination at two different degrees of mouth opening and the effect of anaesthesia applied to the periodontal ligaments.

The dimension discrimination ability of twenty-five young persons was tested at two different degrees of mouth opening. One reference stick of 10-0 mm and another of 45-0 mm was placed between the teeth, alternating with test sticks of different heights. The subjects were asked to assess whether a test stick felt higher or lower than the reference stick. The experiment was performed with and without anaesthesia applied to the periodontal ligaments. Anaesthesia did not impair the discrimination ability. At dimensions in the region of the 10-0 mm stick the incorrect assessments occurred predominantly among sticks higher than the reference stick. Around the 45-0 mm stick incorrect assessments were distributed evenly between dimensions higher or lower than the reference stick.

Adult

Experimental studies on vertical infection of mice with Japanese encephalitis virus. II. Effect of inoculation route on placental and fetal infection.

Studies were made on the effect of the route of inoculation on the establishment of experimental vertical infection of mice with Japanese encephalitis virus. Mice of the three strains, CFW, C3H/He, and C57BL/6, were inoculated with a field strain of the virus by the intravenous, intraperitoneal, or subcutaneous route. An attempt was made on them to recover the virus from the placenta and fetus. As a result, there were differences in rate of plancental and fetal infection among the route of inoculation. It was dependent the establishment of vertical infection. In general, the rates of placental and fetal infection were the highest in the case of intravenous inoculation, the second highest in the case of intraperitoneal inoculation, and the lowest in the case of subcutaneous inoculation, although there were small differences in this tendency among the mouse strains used. The differences in the rates of placental and fetal infection were presumed to be derived not from the difference in the severity of infection of the respective mothers, but from the degree of direct approach of virus to the placenta as one of the factors.

Animals

Experimental studies on vertical infection of mice with Japanese encephalitis virus. I. Effect of mouse strain on placental and fetal infection.

An experiment was carried out with mice to study the effect of the mouse strain on the establishment of experimental vertical infection with Japanese encephalitis virus. Mice of various inbred strains were inoculated with a field strain of virus on the 7th day of pregnancy. An attempt was made on them to recover the virus from the placenta and fetuses. As a result, there were differences in the rate of placental and fetal infection among the mouse strains used. It was clarified that vertical infection could be established experimentally in some selected mouse strains. There was not always a parallel relationship between the rate of placental and fetal infection and the severity of viremia or visceral infection in the dam.

Animals

Immunization of pigs with the attenuated S- strain of Japanese encephalitis virus.

The attenuated S- strain of Japanese encephalitis virus was produced from a wild strain of this virus by serial cultivation in primary bovine kidney cell cultures at 30 degrees C. Pigs were inoculated with it and examined for ability to produce antibody and protect themselves from infection with a wild strain used for challenge. In pigs inoculated with a single dose of 10(6.5) approximately 10(7.5) TCID50 of the S- strain, the neutralizing antibody titer or hemagglutination-inhibiting antibody (HI) titer increased to 10 approximately 320. An antibody titer exceeding 10 was maintained for 2 approximately 9 weeks. In pigs inoculated twice with 10(6.5) approximately 10(7.0) TCID50 of the S- strain, HI titer increased to 80 approximately 640. In many of these pigs, HI titers of 80 approximately 160 persisted for more than 6 weeks. Pigs inoculated once or twice with 10(7.0) approximately 10(7.5) TCID50 of the S- strain were challenged by inoculation with 10(4.5) approximately 10(5.5) TCID50 of a wild strain and examined for the occurrence of viremia. As a result, an ability to protect from infection was demonstrated in pigs which showed an antibody titer surpassing 10 at the time of challenge. Pregnant sows inoculated with 10(7.0) TCID50 of the S- strain were challenged by inoculation with 10(7.0) TCID50 of a wild strain. Neither death nor infection occurred to any fetus harbored by them. From these results, it is concluded that the S- strain can be used as live virus vaccine for porcine practice.

Animals