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T Morimoto

Publications and source records attributed to T Morimoto.

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↗
PubMed2001

Perimetric sensitivity and retinal thickness in eyes with macular edema resulting from branch retinal vein occlusion.

PURPOSE: To document and study the relationship between perimetric sensitivity and retinal thickness at the foveal and parafoveal points in eyes with macular edema associated with branch retinal vein occlusion. METHODS: A prospective study was performed using the central 10-2 Humphrey perimetry program and optical coherence tomography. Seventeen eyes with branch retinal vein occlusion were eligible showing macular edema without macular nonperfusion or massive retinal hemorrhage. RESULTS: The sensitivity and retinal thickness were significantly correlated at the fovea (r = -0.629, P =.006) as well as 1 (r = -0.656, P <.0001) and 3 (r = -0.885, P <.0001) degrees apart from the fovea. The visual acuity that is expressed as a logarithm of the minimum angle of resolution (LogMAR) also correlated with retinal thickness (r = 0.591, P =.011). CONCLUSION: The increased retinal thickness resulting from macular edema is closely correlated with retinal sensitivity as measured by automated static perimetry both at the fovea and parafovea. Measuring the retinal thickness using optical coherence tomography may be useful in monitoring macular edema in eyes with branch retinal vein occlusion.

Adult↗
PubMed2001

Posttransplant function of a nonbeating heart is predictable by an ex vivo perfusion method.

BACKGROUND: We attempted to predict the posttransplant cardiac function of nonbeating donor hearts. METHODS: A total of 13 dogs were studied. Hearts were left in situ for 45 minutes after cardiac arrest caused by exsanguination. Hearts were then excised and reperfused in an ex vivo perfusion apparatus after 60 minutes of warm ischemia to test whether they could eject against an 80 mm Hg afterload from a preload of 10 mm Hg. Thereafter, all hearts were transplanted orthotopically. RESULTS: Four of 13 hearts were able to eject in the apparatus (group A). However, the other nine hearts could not eject under the defined conditions (group B). All four hearts in group A showed good posttransplant hemodynamics (systolic arterial pressure > 80 mm Hg with mean left atrial pressure < 10 mm Hg) without dopamine. However, none of nine hearts in group B could support the circulation without dopamine. CONCLUSIONS: Nonbeating donor heart function evaluated in the perfusion apparatus predicts posttransplant heart function. This method may be applicable for selection of transplantable hearts from nonbeating heart donors.

Animals↗
PubMed2001

Neuronal activity in the putamen and the globus pallidus of rabbit during mastication.

The pattern of jaw movements is changed during a masticatory sequence from ingestion of food to its deglutition. The masticatory sequence is divided into three distinct stages in the rabbit. However, the neural mechanism involved in the alteration of the masticatory stages is still unknown. This study was designed to determine whether neuronal activity in the putamen and globus pallidus is related to the alteration of the masticatory stages. Fifty-three percent of the recorded neurons showed significant alterations of activity during mastication. Of these neurons, 16% changed their firing frequency throughout the masticatory sequence (sequence-related neurons) and 84% changed their firing frequency with the transition of the masticatory stages (stage-related neurons). The stage-related neurons were classified into two groups based on their neuronal activity patterns observed during mastication, i.e. simple type and complex type. The former are the neurons that were either facilitated or inhibited once during mastication, and the latter are those showing the facilitation or inhibition twice or more during mastication. Complex-type neurons were observed more frequently in the globus pallidus than in the putamen. These results suggest that the basal ganglia is involved in mastication and may related to the transition between the masticatory stages.

Animals↗
PubMed2001

Influence of food thickness and hardness on possible feed-forward control of the masseteric muscle activity in the anesthetized rabbit.

The facilitatory masseteric muscle response (FMR) elicited by polyurethane foam strip application between the opposing molars during cortically-induced rhythmic jaw movements (CRJMs) was induced earlier than masticatory force onset. The occurrence of this early response of the FMR (e-FMR) could not be explained by a simple reflex mechanism. One possible mechanism of the e-FMR is the involvement of a feed-forward control mechanism of the masticatory jaw movement. In the present study, experimentally designed polyurethane foam strips with various thickness and hardness were applied during CRJMs and analyzed in terms of how the e-FMR was modulated by the food hardness and thickness. The FMR onset was not related to the strip thickness or the strip hardness. However, the magnitude of the e-FMR increased in a thickness and a hardness-dependent manner. The sensory information of the food properties in the masticatory cycle may make the FMR adequate to chewing of the food in the following cycle, and such modulation may help chewing rhythms remain stable.

Action Potentials↗
PubMed2001

Synthesis of a novel lysophosphatidylcholine.

The novel lysophosphatidylcholine (1), which naturally occurs in the marine sponge Spirastrella abata and was reported to inhibit cholesterol biosynthesis in the Chang liver cell, has been synthesized in four steps from methyl cis-11-octadecenoate (2).

Indicators and Reagents↗
PubMed2001

Relationship of osmotic inhibition in thermoregulatory responses and sweat sodium concentration in humans.

Heat acclimatization improves thermoregulatory responses to heat stress and decreases sweat sodium concentration ([Na(+)](sweat)). The reduced [Na(+)](sweat) results in a larger increase in plasma osmolality (P(osmol)) at a given amount of sweat output. The increase in P(osmol) inhibits thermoregulatory responses to increased body core temperature. Therefore, we hypothesized that the inhibitory effect of plasma hyperosmolality on the thermoregulatory responses to heat stress should be attenuated with the reduction of [Na(+)](sweat) due to heat acclimatization. Eleven subjects (9 male and 2 female) were passively heated by immersing their lower legs into water at 42 degrees C (room temperature 28 degrees C and relative humidity 30%) for 50 min following isotonic or hypertonic saline infusion. We determined the increase in the esophageal temperature (T(es)) required to elicit sweating and cutaneous vasodilation (CVD) (DeltaT(es) thresholds for sweating and CVD, respectively) in each condition and calculated the elevation of the T(es) thresholds per unit increase in P(osmol) as the osmotic inhibition of sweating and CVD. The osmotic shift in the DeltaT(es) thresholds for both sweating and CVD correlated linearly with [Na(+)](sweat) (r = 0.858 and r = 0.628, respectively). Thus subjects with a lower [Na(+)](sweat) showed a smaller osmotic elevation of the DeltaT(es) thresholds for sweating and CVD. These results suggest the possibility that heat acclimatization attenuates osmotic inhibition of thermoregulatory responses as well as reducing [Na(+)](sweat).

Adult↗
PubMed2000

Carbonylative

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Lean body mass and body fat distribution in participants with chronic low back pain.

BACKGROUND: Loss of muscle mass and central obesity progress with aging, but the effect of muscle loss on chronic low back pain has not been precisely evaluated. METHODS: Three hundred thirty Japanese persons aged 45 to 69 years, with a complaint of low back pain for longer than 3 months (n = 203) and age- and sex-matched healthy control subjects (n = 127), were enrolled in this study. Participants with chronic low back pain were classified into the following groups: (1) women with a positive straight leg raise test result, (2) women with a negative straight leg raise test result, (3) men with a positive straight leg raise test result, and (4) men with a negative straight leg raise test result. Controls were classified by sex into a female and a male group. Anthropometric data, consisting of body mass index, percentage body fat, waist-hip ratio, and lean body mass of the upper extremities, trunk, and lower extremities divided by body weight, were measured in participants with low back pain, and the results were compared with those of controls. RESULTS: The waist-hip ratio in women with a negative straight leg raise test result was significantly higher than those in the female control group (P<.001) and in the women with a positive straight leg raise test result (P =.04). The lean body mass of the trunk and lower extremities divided by body weight of women with a negative straight leg raise test result was significantly lower than that of female controls (P =.03 for the trunk and P<.001 for the lower extremities). However, no significant differences were detected between the female negative straight leg raise test result group and the female control group for lean body mass of the upper extremities divided by body weight or body mass index. There were no significant differences in anthropometric data between the male test and control groups or between the female positive straight leg raise test result group and the female control group. CONCLUSION: Trunk and lower extremity loss of muscle mass and central obesity may be risk factors for chronic low back pain without a positive straight leg raise test result in women aged 45 to 69 years. Arch Intern Med. 2000;160:3265-3269.

Adipose Tissue↗
PubMed2000

Identification of two transmembrane regions and a cytosolic domain of rat mitochondrial glycerophosphate acyltransferase.

The topography of rat glycerophosphate acyltransferase (GAT) in the transverse plane of the mitochondrial outer membrane (MOM) was investigated. Computer analysis of the amino acid (aa) sequence derived from rat mitochondrial GAT cDNA (GenBanktrade mark accession nos. and ) predicts the presence of two possible transmembrane domains (aa 473-493 and 574-594) separated by an 80-aa stretch (aa 494-573). To determine the actual orientation of the native protein, we prepared anti-peptide antibodies to three regions: one in between (aa 543-559) and the other two (aa 420-435 and 726-740) flanking the two putative transmembrane regions. Both immunoreaction and immunoprecipitation experiments employing intact and solubilized mitochondria indicate that regions on the N- and C-terminal sides of the transmembrane regions are sequestered on the inner surface of the MOM, while the region between the transmembrane domains is present on the cytosolic face of the MOM. Additionally, two green fluorescent protein (GFP) fusion proteins consisting of full-length GAT fused to GFP at either the C terminus or inserted 115 amino acids from the N terminus were also constructed to determine the orientation of the N and C termini. COS-1 cells expressing these fusion proteins were fractionated to obtain mitochondria. Protease digestion of intact and solubilized COS-1 cell mitochondria revealed that the GFP domains of these fusion proteins are sequestered on the inner side of the MOM. The present findings indicate that GAT is a dual-spanning, transmembrane protein adopting an inverted "U" conformation in the transverse plane of the MOM, where the N and C termini are sequestered on the inner surface of the MOM, while aa 494-573 are exposed on the cytosolic surface of the MOM.

Animals↗
PubMed2000

Prenatal DNA diagnosis of a single-gene disorder from maternal plasma.

Achondroplasia is a short-limb disorder caused by a point mutation in a single gene. To diagnose such a disorder prenatally requires the use of invasive procedures such as amniocentesis. However, using PCR and restriction fragment length polymorphism analysis, we were able to detect the mutation in the plasma of a woman carrying a fetus suspected of having achondroplasia. The detection of a fetus-derived mutant gene from maternal plasma may therefore permit non-invasive prenatal diagnosis of single-gene disorders.

Achondroplasia↗
PubMed2000

A p300 protein as a coactivator of GATA-6 in the transcription of the smooth muscle-myosin heavy chain gene.

The mechanisms that regulate smooth muscle development and differentiation are poorly understood. Although recent studies have suggested the possible role of a zinc finger transcription factor, GATA-6, in the differentiation of vascular smooth muscle cells (VSMCs), the downstream gene targeted by GATA-6 is unknown. The expression of smooth muscle-myosin heavy chain (Sm-MHC) provides a highly specific marker for the differentiated phenotype of VSMCs as well as the smooth muscle cell lineage. Here, we show that GATA-6 bound to a GATA-like motif (-810/-805) within the rat Sm-MHC promoter in a sequence-specific manner and activated this promoter through this site. In addition, we show that the transcriptional coactivator p300 associated with GATA-6 during the transcription of the Sm-MHC gene. A p300/GATA-6 complex in VSMCs was up-regulated by induction of the quiescent phenotype. A wild-type E1A, which interferes with endogenous p300, but not a mutant E1A defective for p300 binding, markedly down-regulated the expression of endogenous Sm-MHC in quiescent-phenotype VSMCs. These studies provide the first identification of a functionally important GATA-6 binding site within a smooth muscle-specific promoter and suggest a role for p300 in the maintenance of the differentiated phenotype in VSMCs as a coactivator of GATA-6.

Adenovirus E1A Proteins↗
PubMed2000

DELETEile chiral bidentate ligands derived from alpha-amino acids: synthetic applications and mechanistic considerations in the palladium-mediated asymmetric allylic substitutions.

A new class of chiral amidine-phosphine hybrid ligands 7a,b, which are readily accessible from the corresponding alpha-amino acids, were developed. A versatility for construction of new ligands is desirable, by which a variety of reactions and substrates become applicable. Indeed, a variety of modifications, such as exchange reactions to other amino groups in the amidine skeleton and the production of other types of ligands, are possible using the precursor compounds of 7a. Thus, novel chiral ligands 7c,d, 8, 11, and 13, which provide sterically and electronically different chiral circumstances, were prepared and used for the palladium-mediated asymmetric allylic substitutions of both acyclic and cyclic compounds. In these reactions, high levels of asymmetric induction were achieved for both substrates. A marked advancement of reactivity and enantioselectivity in palladium-catalyzed asymmetric allylations of 1,3-diphenylpropen-2-yl pivalate 14a was attained by examination of electronic substituent effects in a new series of chiral P-N and S-N hybrid ligands 8 and 11. Mechanistic views concerning the enantiodiscriminating step were demonstrated, in which a good correlation between a novel Pr/Mr concept and the absolute configuration of allylation products are discussed for the prediction of enantioselecting direction. The use of ketene silyl acetals as nucleophiles was investigated and compared with the corresponding harder anionic carbon nucleophiles. The former nucleophiles afforded higher enantioselectivity in asymmetric allylic transformations of 14a.

Alkaloids↗
PubMed2000

Different disruptive effects on the acquisition and expression of conditioned taste aversion by blockades of amygdalar ionotropic and metabotropic glutamatergic receptor subtypes in rats.

Conditioned taste aversion (CTA) is based on the gustatory long-term memory established after association of the taste of food (conditioned stimulus, CS) with visceral signals of poisoning (unconditioned stimulus, US). After the acquisition of CTA, hedonics of the taste CS changes from positive to negative as indicated by reduced ingestive and increased aversive taste reactivities in response to re-exposures to the CS. We examined the effects of reversible and selective blockades of the amygdalar glutamate receptor subtypes, AMPA, NMDA and metabotropic glutamate receptors, on the formation of CTA. Blockades of each of the three receptor subtypes between ingestion of saccharin (CS) and malaise-inducing LiCl (US) disrupted the acquisition of CTA. After the acquisition of CTA, however, blockades of only AMPA receptors, but not NMDA or metabotropic receptors, impaired the expression of CTA. This effect was seen only during the period when the antagonistic action to AMPA receptors lasted. These results indicate that both ionotropic and metabotropic glutamate receptor subtypes in the amygdala are indispensable for the acquisition of CTA, but that the expression of acquired CTA is mediated only by AMPA receptors. The present results also suggest that the amygdalar glutamatergic neural transmission is involved in the formation and storage of long-term gustatory memory associated with the altered hedonics from positive to negative.

Amygdala↗
PubMed2000

Leptin facilitates histamine release from the hypothalamus in rats.

We studied the effect of leptin on the release of histamine from the anterior hypothalamus using an in vivo microdialysis in anesthetized rats. Histamine release was significantly increased by leptin administration (1.3 mg/kg, i.p.) and kept at a high level for 4 h after the injection. The same dose of leptin significantly reduced food intake in another group of rats. This finding suggests that leptin activates the histaminergic system in the hypothalamus, which may contribute the expression of leptin-induced anorectic effect.

Animals↗
PubMed2000

Phosphorylation of GATA-4 is involved in alpha 1-adrenergic agonist-responsive transcription of the endothelin-1 gene in cardiac myocytes.

The expression of endothelin-1 (ET-1) in cardiac myocytes is markedly induced during the development of heart failure in vivo and by stimulation with the alpha(1)-adrenergic agonist phenylephrine in culture. Although recent studies have suggested a role for cardiac-specific zinc finger GATA factors in the transcriptional pathways that modulate cardiac hypertrophy, it is unknown whether these factors are also involved in cardiac ET-1 transcription and if so, how these factors are modulated during this process. Using transient transfection assays in primary cardiac myocytes from neonatal rats, we show here that the GATA element in the rat ET-1 promoter was required for phenylephrine-stimulated ET-1 transcription. Cardiac GATA-4 bound the ET-1 GATA element and activated the ET-1 promoter in a sequence-specific manner. Stimulation by phenylephrine caused serine phosphorylation of GATA-4 and increased its ability to bind the ET-1 GATA element. Inhibition of the extracellularly responsive kinase cascade with PD098059 blocked the phenylephrine-induced increase in the DNA binding ability and the phosphorylation of GATA-4. These findings demonstrate that serine phosphorylation of GATA-4 is involved in alpha(1)-adrenergic agonist-responsive transcription of the ET-1 gene in cardiac myocytes and that extracellularly responsive kinase 1/2 activation plays a role upstream of GATA-4.

Adrenergic alpha-1 Receptor Agonists↗