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Biomedical subjects

M Takahashi

Publications and source records attributed to M Takahashi.

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↗
PubMed1979

Non-specific interactions of CRP from E. coli with native and denatured DNAs: control of binding by cAMP and cGMP and by cation concentration.

The cyclic adenosine 3',5'-monophosphate receptor protein of Escherichia coli (CRP) binds cooperatively to single- and double-stranded DNA. Binding data could be fitted to the model of McGhee and von Hippel (1) and show that neither strandedness of DNA, nor the effectors cAMP and cGMP or the ionic strength (KCl) do change appreciably the cooperativity parameter omega (omega approximately or equal to 100), and site size of DNA. Instead, distinctly different slopes were observed for the linear decrease of log K omega (a measure of the overall affinity) as a function of log (K+). From these double-log plots (2), the number of cations released and the non-electrostatic contributions to the binding free energy could be determined. Binding of CRP to single-stranded DNA is slightly favored under physiological ionic conditions (0.15-0.20 M), but such a preferential binding is almost abolished in the presence of cAMP which increases the strength of the interaction of the protein with both forms of DNA. CGMP does not change the binding properties and interactions of CRP with DNA. These observations do not support the proposal that the cAMP-CRP complex could stimulate transcription via some "melting" property unless its interactions be dramatically changed when it binds specifically to promoter DNA.

Bacteriophage lambda↗
PubMed1979

Erythrophagocytosis by the sinus endothelial cell of the spleen in haemolytic anaemias.

An ultrastructural study of spleens from patients with a heterogeneous group of haemolytic anaemias was undertaken in order to determine whether sinus endothelial cells have erythrophagocytic ability. In most cases, sinus endothelial cells contained erythrocytes and various stages of intracellular degradation of engulfed erythrocytes were noted. Though the frequency of erythrophagocytosis varied from case to case, phagocytosis of erythrocytes by the endothelial cell was more frequent in cases in which cordal macrophages showed active erythrophagocytosis. These results suggest that the sinus endothelial cells have erythropagocytic ability in certain pathological states, especially when the demands for the removal of defective erythrocytes are increased. However, the bulk of erythrophagocytosis is carried out by cordal macrophages, and endothelial phagocytosis has a minor significance in the developemnt of haemolytic anaemia. Two possible processes by which erythrocytes come into contact with sinus endothelial cells are suggested.

Anemia, Hemolytic↗
PubMed1979

[Cooperative non-specific binding of the cyclic adenosine 3'--5'-monophosphate receptor protein (CRP) from Escherichia coli to double-stranded thymus and lambda pgal DNA].

Either free or combined with cAMP, CRP binds cooperatively to double-stranded thymus and lambda pgal DNA. The affinity of CRP for both DNAs in these non-specific interactions is increased by cAMP without noticeable change in the degree of cooperativity. Values of the intrinsic association constant, cooperativity parameter, and site size of DNA were determined from ultracentrifugal investigations under near-physiological ionic conditions.

Animals↗
PubMed1979

Immediate postembolization excision of glomus jugulare tumors: advantages of new combined techniques.

Preoperative percutaneous transfemoral catheter embolization of feeding vessels in glomus jugulare tumors, followed by immediate application of standard surgical techniques, presents the treatment of choice, allowing meticulous microsurgery with virtually complete hemostasis. Therefore, the surgeon can operate in a bloodless environment throughout the compressed and intricate anatomic field, amidst such important yet vulnerable structures as cranial nerves, inner ear, carotid artery, jugular bulb, venous sinuses, and dura, while reducing surgical error and functional deficit for the patient. Review of the last 11 cases of glomus jugulare tumors at UCLA shows that even extensive Alford grade 2 tumors of the middle ear, jugular bulb, and mastoid had only minor blood losses with this combined technique of embolization-immediate surgery, as compared with earlier surgical methods. Pertinent literature on glomus jugulare and its treatment is reviewed. Combined embolization and immediate surgery offer the best approach for treatment of resectable glomus jugulare tumors.

Adult↗
PubMed1979

Attenuated mumps virus therapy of carcinoma of the maxillary sinus.

This paper presents treatment of carcinoma of the maxillary sinus with an attenuated mumps virus. The mumps virus was inoculated into two cases of very advanced carcinoma of the maxillary sinus by local and general injection. Shortly after injection, relief from severe cancer pain and growth inhibition or necrosis of tumor were observed in both cases. In this communication, we discuss a possible mechanism of antitumor effect of mumps virus by utilizing immunologic tests and interferon assay.

Carcinoma, Squamous Cell↗
PubMed1979

Factors causing the clumping reaction of streptococcal strains with human plasma.

Fresh isolates of 204 strains of Streptococcus haemolyticus, 75 strains of viridans group Streptococcus, and 45 strains of Streptococcus pneumoniae were studied for their clumping reactions with human plasma. The plasma and serum factors that clumped the streptococcal strains were compared with those that clumped a Staphylococcus aureus strain. One hundred eleven strains of S. haemolyticus, 10 strains of viridans group Streptococcus, and none of the strains of S. pneumoniae tested were clumped by human plasma. However, clumping activity was remarkably unstable after subculturing on plates containing Todd-Hewitt blood agar. The strain with the highest level of activity was clumped by fibrinogen and normal human serum. Results of tests of the clumping reactions of staphylococci and streptococci with human serum indicated that the serum factors responsible for those reactions may be identical.

Bacteriological Techniques↗
PubMed1979

Kinetic properties of dynein ATPase from Tetrahymena pyriformis. The initial phosphate burst of dynein ATPase and its interaction with ATP analogs.

1. Dynein was extracted with 0.5 M KCl from Tetrahymena axonemes. SDS-gel electrophoresis of the extract indicated that about 50% of the extracted protein had a molecular weight of about 3.5 X 10(5), and that 90% of the proteins with this weight had been extracted. 2. The ATPase [EC 3.6.1.3] reaction of the KCl-extracted dynein fraction was enhanced by 60-80% by addition of the outer doublet fraction. It showed an initial burst of Pi liberation of about 1 mol per mol of proteins with a molecular weight of 3.5 X 10(5). 3. We examined the interaction of the dynein-tubulin system from Tetrahymena cilia with ten ATP analogs [2'-dATP, 3'-dATP, epsilonATP, FTP, 8-NH(CH3)-ATP, 8,3'-S-cyclo-ATP, 8-Br-ATP, 8-OCH3-ATP, 8-SCH3-ATP, and AMPPNP]. Among them, 2'-dATP and 3'-dATP were good substrates for dynein ATPase, as they induced the dissociation of dynein arms from the B-tubule of outer doublets, the sliding movement between outer doublets, and the bending movement of axonemes. The other analogs did not induce the dissociation or the sliding movement. 4. Among the ATP analogs tested, only 2'-dATP and 3'-dATP induced the reorientation of cilia on the Triton model of Tetrahymena; the reorientation rates were smaller than that induced by ATP.

Adenosine Triphosphatases↗
PubMed1979

Alpha-fetoprotein producing rhabdomyosarcoma of the adult liver.

An autopsy case of a rare primary tumor in a 76-year-old man is described. The tumor is histologically comprised of rhabdomyoblasts massively infiltrating without any epithelial elements referable to be as hepatoma. There was no evidence that regarded the hepatic tumor as metastatic secondary tumor in histological examination of other organs. Furthermore, interesting was the production of alpha-fetoprotein from the tumor cells that was detected by immunofluorescent antibody technique. Review of the literature on primary liver rhabdomyosarcomas or adult hepatoblastomas shows no similar case.

Aged↗
PubMed1979

Effect of macular ablation on vertical optokinetic nystagmus in the squirrel monkey.

After macular ablation in squirrel monkeys, a significant improvement of the slow-phase eye speed of vertical optokinetic nystagmus (VOKN) was found. This findings is in contrast to the result of our previous study in which horizontal optokinetic nystagmus (HOKN) was not improved following macular ablation. The different influence of macular ablation on HOKN and VOKN could be due to the directional characteristics of vestibular and visual interaction relative to the direction of gravity and to the difference in horizontal and vertical vestibulo-oculomotor neural pathways, including vestibular end-organs. The vertical directional dominance which was observed preoperatively was similarly observed in the postablative status; the upward slow-phase nystagmus was easier to provoke than the downward nystagmus by application of an identical stimulus.

Acoustic Maculae↗
PubMed1979

Effect of exercise upon locomotor balance modification after peripheral vestibular lesions (unilateral utricular neurotomy) in squirrel monkeys.

In this study, we placed unilateral utricular nerve section and measured the locomotor equilibrium function (deviation counts of the animal's trotting gait) by the squirrel monkey platform runway test. We applied physical exercise, both preoperatively (3 weeks) and postoperatively. 21 young adult squirrel monkeys were randomly assigned to three groups (7 each): rotating cage exercise (continuous trotting in the motor-driven rotating cage) group, rail-traversing exercise (60 running shuttles on the rotating rail) group, and control nonexercise group. After the statistical analyses on data it was found that the physical exercise showed some effect; however, the type, daily amount, and number of days applied must be quite substantial.

Animals↗
PubMed1979

Radioimmunoassay of methionine enkephalin and interference by brain factor of immunoreactivity and opiate receptor binding activity.

We developed a radioimmunoassay of methionine-enkephalin (met-enk) which was found to be highly specific to the peptide and 1 pmol was the detection limit. Interference by the following peptides was practically negligible; leucine-enkephalin, LAP- or CNBr-treated met-end, alpha- and beta-endorphins. Morphine and its congeners were totally inert. Measurement of met-enk in rat brain P2 fraction revealed besides met-enk, the presence of the factor which cross-reacted with the antiserum and also appeared to bind with the brain opiate receptor. Though the nature of the factor has not yet been characterized, it is suggested that for qualitative assessment of the tissue level of met-enk, a method to selectively inactivate either the peptide or the factor should be developed first.

Animals↗
PubMed1979

Effects of adrenergic agonists and antagonists on immediate cutaneous reactions in bronchial asthma.

Asthmatic patients who showed an allergic skin reaction to house-dust antigen (HD) were injected intradermally with a mixture of HD and a various dose of isoproterenol (Isopr) or propranolol (Propr). In some cases Isopr clearly suppressed the formation of the wheal, but in some others Isopr did not much affect the allergic skin reaction. Also Propr increased markedly the skin reaction of some patients, or had little effect on it. The sensitivity of the skin of asthmatic patients to these drugs was closely correlated with the general response of the patients to adrenaline, such as changes in heart rate, diastolic blood pressure, blood glucose level, and blood triglyceride level.

Adrenergic Agonists↗
PubMed1979

Japanese encephalitis virus in mosquito salivary glands.

Culex tritaeniorhynchus and C. pipiens mosquitoes were infected with Japanese encephalitis virus either by intrathoracic injection or by membrane feeding. The virus maturation sites and the process of virus particle concentration in salivary gland cells were studied by electron microscopy. Occurrence of mature virions was primarily associated with intracytoplasmic viral matrices which were extraordinarily large and had a perinuclear location in C. pipiens mosquitoes. The other sign of virus replication was the proliferation of small spherical vesicles throughout the cytoplasm. It appeared that mature virions were entrapped in intracellular vacuoles and later released into the apical cavity of salivary gland cells through the fusion of these vacuoles with the apical plasma membrane. This process seemed to be associated with primary resynthesis of saliva in mosquitoes following blood feeding activity. Another type of shedding involved virus particles either singly or in mass being released directly through the apical plasma membrane. All of these events occurred only in cells of the lateral lobes of the salivary glands, which fact was confirmed by immunofluorescent staining of infected glands. The median lobe of mosquito salivary glands may have a minor or no role in the transmission of Japanese encephalitis virus.

Animals↗
PubMed1979

[Effect of combination of hetacillin, cephapirin and amikacin (author's transl)].

With the investigations of the effect of combination of hetacillin, cephapirin and amikacin, following experimental results were obtained; 1. Effect of combination of amikacin, cephapirin and hetacillin was differed depending upon the genus and species of bacteria. However, in general, in the cases showing effective results there was a relation in the concentration of these antibiotics. With strains of Escherichia coli amikacin and cephapirin was cooperative, but not with other combinations and strains of Proteus showed similar tendencies to those strains. In the strains of Pseudomonas, no effect was observed with these antibiotics. However, significant cooperative effect was shown in strains of Klebsiella pneumoniae. In penicillin-resistant strains of Staphylococci cooperative effect was represented only a combination of amikacin and hetacillin. 2. Amikacin was resistant against penicillinase isolated from penicillin-resistant strain of Staphylococcus and cephalosporinase extracted from cephalosporin-resistant strain of Escherichia coli. 3. When a strain of K. pneumoniae, showing cooperative effect with amikacin and cephapirin, was examined by electronmicroscopy, enlargement of cells and destruction of the cell walls were observed.

Amikacin↗