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Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 19 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↗

Intranuclear paracrystals observed in striated muscle specific LIM protein-deficient mouse cardiomyocytes.

A paracrystalline structure was observed within left ventricular cardiomyocyte nuclei of MLP(-/-) mice. The paracrystal possessed cross lines, approximately 8.0 micro m long and 0.3 micro m wide, with a slender spindle shape and a periodicity of 13 nm. Paracrystals were best observed along the longitudinal orientation of myofibrils and were detected in less than 10% of the nuclei observed. One dimension of the protein unit forming the paracrystal was 8.5 nm long. The electron density of the paracrystal appeared to be slightly higher than that of heterochromatin, suggesting that RNA-associated proteins are constituents of the paracrystal. This is the first report of intranuclear paracrystals in cardiomyocytes, which appear to be unique to MLP(-/-) mice.

Animals↗

The cytoskeleton in the unique cell reproduction by conidiogenesis of the long-neck yeast Fellomyces (Sterigmatomyces) fuzhouensis.

The morphology of conidiogenesis and associated changes in microtubules, actin distribution and ultrastructure were studied in the basidiomycetous yeast Fellomyces fuzhouensis by phase-contrast, fluorescence, and electron microscopy. The interphase cell showed a central nucleus with randomly distributed bundles of microtubules and actin, and actin patches in the cortex. The conidiogenous mother cell developed a slender projection, or stalk, that contained cytoplasmic microtubules and actin cables stretched parallel to the longitudinal axis and actin patches accumulated in the tip. The conidium was produced on this stalk. It contained dispersed cytoplasmic microtubules, actin cables, and patches concentrated in the cortex. Before mitosis, the nucleus migrated through the stalk into the conidium and cytoplasmic microtubules were replaced by a spindle. Mitosis started in the conidium, and one daughter nucleus then returned to the mother via an eccentrically elongated spindle. The cytoplasmic microtubules reappeared after mitosis. A strong fluorescence indicating accumulated actin appeared at the base of the conidium, where the cytoplasm cleaved eccentrically. Actin patches then moved from the stalk together with the retracting cytoplasm to the mother and conidium. No septum was detected in the long neck by electron microscopy, only a small amount of fine "wall material" between the conidium and mother cell. Both cells developed a new wall layer, separating them from the empty neck. The mature conidium disconnected from the empty neck at the end-break, which remained on the mother as a tubular outgrowth. Asexual reproduction by conidiogenesis in the long-neck yeast F. fuzhouensis has unique features distinguishing it from known asexual forms of reproduction in the budding and fission yeasts. Fellomyces fuzhouensis develops a unique long and narrow neck during conidiogenesis, through which the nucleus must migrate into the conidium for eccentric mitosis. This is followed by eccentric cytokinesis. We found neither an actin cytokinetic ring nor a septum in the long neck, from which cytoplasm retracted back to mother cell after cytokinesis. Both the conidium and mother were separated from the empty neck by the development of a new lateral wall (initiated as a wall plug). The cytoskeleton is clearly involved in all these processes.

Actins↗

Prediction of blood glucose level of type 1 diabetics using response surface methodology and data mining.

In order to improve the accuracy of predicting blood glucose levels, it is necessary to obtain details about the lifestyle and to optimize the input variables dependent on diabetics. In this study, using four subjects who are type 1 diabetics, the fasting blood glucose level (FBG), metabolic rate, food intake, and physical condition are recorded for more than 5 months as a preliminary study. Then, using data mining, an estimation model of FBG is obtained, and subsequently, the trend in fluctuations in the next morning's glucose level is predicted. The subject's physical condition is self-assessed on a scale from positive (1) to negative (5), and the values are set as the physical condition variable. By adding the physical condition variable to the input variables for the data mining, the accuracy of the FBG prediction is improved. In order to determine more appropriate input variables from the biological information reflecting on the subject's glucose metabolism, response surface methodology (RSM) is employed. As a result, using the variables exhibiting positive correlations with the FBG in the RSM, the accuracy of the FBG prediction improved. Conditions could be found such that the accuracy of the predicting trends in fluctuations in blood glucose level reached around 80%. The prediction method of the trend in fluctuations in the next morning's glucose levels might be useful to improve the quality of life of type 1 diabetics through insulin treatment, and to prevent hypoglycemia.

Adult↗

Dot-blot-SNP analysis for practical plant breeding and cultivar identification in rice.

We report dot-blot hybridization with allele-specific oligonucleotides for single nucleotide polymorphisms (SNPs) analysis to be applicable for practical plant breeding and cultivar identification. Competitive hybridization of a digoxigenin-labeled oligonucleotide having the sequence of a mutant allele (or a wild-type allele) together with an unlabeled oligonucleotide having the sequence of a wild-type allele (or a mutant allele) was highly effective to reduce background signals in dot-blot hybridization. All 100 tested genes (200 alleles) in rice having SNPs or insertions/deletions were detected in an allele-specific manner. Genotypes of 43 rice cultivars were identified by this technique, and eight SNP markers were found to be sufficient for distinguishing all the cultivars from each other. Dot-blot analysis was also applied to genotyping of Wx and Sd1 of F4 plants in a conventional breeding program. Since dot-blot analysis with competitive hybridization provides a highly reliable, simple, and cost-effective technique for SNP analysis of a large number of samples, this technique is expected to realize the practical use of a novel breeding method, in which plants or breeding lines are selected by SNP analyses of many genes in a laboratory.

Alleles↗

Derivatization chemistries for determination of serotonin, norepinephrine and dopamine in brain microdialysis samples by liquid chromatography with fluorescence detection.

The present paper provides an overview on currently developed derivatization chemistries and techniques for determination of monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE) and dopamine (DA) in microdialysis samples by microbore liquid chromatography with fluorescence detection. In mild alkaline conditions, 5-hydroxyindoles and catecholamines react with benzylamine (BA), forming highly fluorescent 2-phenyl-4,5-pyrrolobenzoxazoles and 2-phenyl(4,5-dihydropyrrolo) [2,3-f]benzoxazoles, respectively. However, for derivatization of DA a higher fluorescence intensity was achieved for reaction with 1,2-diphenylethylenediamine (DPE) rather than with BA, therefore for simultaneous determination of 5-HT, NE and DA in brain microdialysates, a two-step derivatization with BA followed by DPE was developed. The detection limits for 5-HT, NE and DA were 0.2, 0.08 and 0.13 fmol, respectively, in an injection volume of 20 microL, which corresponds to concentrations of 30, 12 and 19.5 pm, respectively in standard solution prior to derivatization. The experimental data presented demonstrate the ability of the technique to simultaneously monitor neuronally releasable pools of monoamine neurotransmitters in the rat and mouse brains at basal conditions and following pharmacological treatments or physiological stimuli. These techniques play an important role in drug discovery and clinical investigation of psychiatric and neurological diseases such as depression, schizophrenia and Parkinson's disease.

Brain↗

Substance P stimulates release of RANKL via COX-2 expression in human dental pulp cells.

OBJECTIVE: Our previous study found that substance P (SP), a sensory neuropeptide, was expressed in the dental pulp of rats during experimental tooth movement. We examined the effects of SP on the production of prostaglandin (PG) E2 and the receptor activator of nuclear factor- B ligand (RANKL) by human dental pulp fi broblast-like (HDPF) cells. MATERIALS AND METHODS: SP was added to cultured HDPF cells at concentrations ranging from of 10(-4) to 10(-12) mol/L. PGE2 and soluble RANKL (sRANKL) levels were determined using enzyme-linked immunosorbent assay kits. Gene expression was confi rmed by RT-PCR analysis. Pit formation assays using dentin slices were carried out to examine the effect of SP on osteoclastogenesis. RESULTS: The levels of PGE2 and sRANKL increased in the presence of SP, though the increases were greater in the experimental groups in both a time- and concentration-dependent manner, and the increase of RANKL was partially mediated by PGE2. The gene expression of cyclooxygenase (COX)-2 and RANKL was up-regulated, and conditioned medium samples obtained from HDPF cells treated with SP induced bone resorption. CONCLUSIONS: SP stimulated the production of PGE2 and RANKL, and promoted bone resorption. Therefore, SP may be involved in pulpal inflammation and root resorption during orthodontic tooth movement.

Adolescent↗

Levels of RANKL and OPG in gingival crevicular fluid during orthodontic tooth movement and effect of compression force on releases from periodontal ligament cells in vitro.

OBJECTIVE: To determine the levels of the receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) during orthodontic tooth movement. A second objective was to investigate the effect of compression force on RANKL and OPG production from human periodontal ligament (hPDL) cells. DESIGN: Ten adolescent patients were included. GCF was collected at the distal cervical margins of the experimental and control teeth 0, 1, 24, and 168 h after the retracting force was applied. Thisin vitro study was performed to examine the secretion of RANKL and OPG from hPDL cells following a compression force (0, 0.5, 1.0, 2.0, or 3.0 g/cm(2) for 48 h). Enzyme-linked immunosorbent assay (ELISA) kits were used to determine RANKL and OPG levels in the GCF and the conditioned medium. RESULTS: GCF levels of RANKL were significantly higher, and the levels of OPG significantly lower, in the experimental canines than in the control teeth at 24 h, but there were no such significant differences at 0, 1, or 168 h. In vitro study indicated that the compression force significantly increased the secretion of RANKL and decreased that of OPG in hPDL cells in a time- and force magnitude-dependent manner. The compression-stimulated secretion of RANKL increased approximately 16.7-fold and that of OPG decreased 2.9-fold, as compared with the control. CONCLUSIONS: The results obtained suggest that the changes of amount of RANKL and OPG may be involved in bone resorption as a response to compression force.

Adolescent↗

Effects of aging on RANKL and OPG levels in gingival crevicular fluid during orthodontic tooth movement.

OBJECTIVES: To compare the levels of the receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) during orthodontic tooth movement in juvenile and adult patients. DESIGN: Fifteen juveniles and 15 adults served as subjects. GCF was collected from the distal cervical margins of the experimental and control teeth at 0, 1, 24, and 168 h after application of a retracting force. Enzyme-linked immunosorbent assay kits were used to determine RANKL and OPG levels in the GCF samples. RESULTS: The amount of tooth movement for juveniles was larger than for adults after 168 h. Further, after 24 h RANKL levels were increased and those of OPG decreased in GCF samples from the compression side during orthodontic tooth movement in both juveniles and adults. The RANKL/OPG ratio in GCF from adult patients was lower than that in the juvenile patient samples. CONCLUSION: Our results suggest that the age-related decrease in amount of tooth movement may be related to a decrease in RANKL/OPG ratio in GCF during the early stages of orthodontic tooth movement.

Adolescent↗

RANKL increase in compressed periodontal ligament cells from root resorption.

The ligand receptor activator of NFkappaB (RANKL) plays an important role in osteoclast formation. However, very little is known about the relationship between external apical root resorption during orthodontic treatment and RANKL. We hypothesized that compressive force is responsible for RANKL formation and up-regulation of osteoclastogenesis in periodontal ligament (PDL) cells from patients with severe orthodontically induced external apical root resorption. RANKL and osteoprotegerin (OPG) production, TRAP-positive cells, and resorptive pits were determined. The increase of RANKL and the decrease of OPG were greater in the severe root resorption group than in the non-resorption group. The numbers of TRAP-positive cells and resorptive pits were also increased in the severe root resorption group than in the non-resorption group. These results support the hypothesis that the compressed PDL cells obtained from tissues with severe external apical root resorption may produce a large amount of RANKL and up-regulate osteoclastogenesis.

Adolescent↗

High sensitivity C-reactive protein in asthma.

Asthma is characterised by chronic inflammation of the airways, but the relevance of high-sensitivity assays for C-reactive protein (hs-CRP), which are known to be a sensitive marker of low-grade systemic inflammation, has not been fully studied in asthma. The objective was to examine serum hs-CRP levels in patients with asthma and their relationship to clinical characteristics and degree of airway inflammation. Serum hs-CRP levels were cross-sectionally examined in steroid-naive (n = 22) and steroid-inhaling (n = 23) adult patients with asthma and healthy controls (n = 14). All were nonsmokers. Serum hs-CRP levels were significantly increased in steroid-naive patients (mean+/-sd 1.33+/-1.48 mg.L(-1)) compared with controls (0.21+/-0.30 mg.L(-1)), but not in patients on inhaled corticosteroid. Among steroid-naive patients, serum hs-CRP levels significantly negatively correlated with indices of pulmonary function (forced expiratory volume in one second/forced vital capacity and forced mid-expiratory flow) and positively with sputum eosinophil count. Among patients on inhaled corticosteroid, hs-CRP levels did not correlate with any indices. In conclusion, an increase in serum C-reactive protein levels measured by high-sensitivity assays may be associated with airflow obstruction and airway inflammation, and may serve as a surrogate marker of airway inflammation in asthma.

Adult↗

[Diastolic heart failure in patients with aortic valve disease].

From March 2002 to August 2005, 53 patients with age between 30 and 86 underwent surgical treatment for aortic valve disease. Preoperative diastolic heart failure was observed in 15 cases (28.3%). Operative procedures consisted of aortic valve replacement (AVR) in 42 cases [AVR and mitral valve replacement (MVR) in 3], aortic valve plasty (AVP) in 2, and aortic root replacement in 4. Concomitant procedures included maze procedure in 2 cases, coronary artery bypass grafting (CABG) in 6, mitral valve surgery in 15, and tricuspid valve annuloplasty (TAP) in 8. There were 7 cases for patient-prosthesis mismatch (PPM) [13.2%]. There were 2 hospital deaths (both were low-output syndrome). Among the surgical survivors, there were 2 late cardiac-related complications (all cases were cardiac failure). There was no recurrence or re-operation. Although all cases had severe diastolic failure, their systolic function was almost normal. Our study suggested that in patients with aortic valve disease, not PPM but diastolic heart failure correlated strongly with postoperative event and survival.

Aged↗

[Mitral valve plasty through right thoracotomy with submammary skin incision].

A 30-year-old female with congestive heart failure was referred to our hospital and massive mitral regurgitation was detected on the echocardiography. She was a mother of 2 infants, and wished early recovery from surgery, cosmetic consideration to skin incision and future pregnancy. Her mitral valve was successfully repaired through right thoracotomy with submammary skin incision. Postoperative transthoracic Doppler echocardiography revealed no mitral regurgitation. The patient recovered uneventfully and was discharged on the 8th postoperative day. And she has been drug-free since then.

Adult↗

Psychophysical analysis of monitor display functions affecting observer diagnostic performance of CT image on liquid crystal display monitors.

The aim of the present study was to propose suitable display functions for CT image representation on liquid crystal display (LCD) monitors by analyzing the characteristics of the monitor's typical display functions using psychophysical analysis. The luminance of the LCD monitor was adjusted to a maximum of 275 cd/m2 and 480 cd/m2. Three types of postcalibrated display functions (i.e., GSDF, CIELAB, and Exponential gamma 2.2) were evaluated. Luminance calculation of a new grayscale test pattern (NGTP) was done for the conversion of the digital driving level (DDL) into the CT value. The psychophysical gradient delta of display functions for the CT value was evaluated and compared via statistical analysis. The delta value of GSDF and CIE decreased exponentially; however, the delta value of Exponential gamma 2.2 showed a convex curve with a peak at a specific point. There was a statistically significant difference among the delta values of the three types of display functions on the 480 cd/m2 maximum via Kruskal Wallis test (P<0.001). The GSDF was suitable for observation of abdominal and lung CT images; however, the display function combined the Exponential gamma 2.2 and the GSDF functions and was ideal for observation of brain CT images by psychophysical analysis.

Brain↗

Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy.

To assess the etiology of influenza-associated encephalopathy (IAE), a surveillance effort was conducted during 2000-2003 in South-West Japan. All fatal and handicapped patients except one (4/34 patients) exhibited a disorder of mitochondrial beta-oxidation evoked by the inactivated carnitine palmitoyltransferase II (CPT II) with transiently elevated serum acylcarnitine ratios (C(16:0) + C(18:1))/C(2) > 0.09 during high-grade fever. Analyses of genotypes and allele compositions of CPT II revealed a thermolabile phenotype of compound heterozygotes for [1055T > G/F352C] and [1102G > A/V368I], which shows a higher frequency in IAE patients than healthy volunteers (P < 0.025). The thermolabile phenotype of CPT II variations may be a principal genetic background of IAE in Japanese.

Adolescent↗

Evaluation of grey-scale standard display function as a calibration tool for diagnostic liquid crystal display monitors using psychophysical analysis.

The digital imaging and communications in medicine (DICOM) standard proposed the grey-scale standard display function (GSDF) as a calibration tool for making the gradation characteristic of a radiographic output image consistent. This is designed in such a manner that the contrast visually recognised by observers (called psychophysical contrast) becomes a constant for all digital driving levels. The DICOM standard calls such an ideal characteristic perceptual linearisation. The psychophysical gradient that can express the psychophysical contrast was introduced for the evaluation of the GSDF using a liquid crystal display monitor. Investigations regarding its ability to yield a constant psychophysical contrast, independent of the digital driving level change and under an actual observation environment, such as for clinical radiographic diagnosis in hospital, were carried out. The psychophysical gradients of the GSDF were obtained for two kinds of observation environment: one was a restricted environment such as in a dark room, under steady-state adaptation, using the sinusoidal grading pattern corresponding to the peak frequency of the human eye response. The other was an actual environment reflecting that encountered during clinical diagnosis in a hospital. As a result, the psychophysical gradient under the restricted environment became almost constant and independent of the change in digital driving level, i.e. perceptual linearisation could be satisfied. Furthermore, under the actual observation environment, the psychophysical gradient decreased gradually with the increase in digital driving level, i.e. the perceptual linearisation could not be satisfied. The percentage decrease in the value of the psychophysical gradient at the maximum luminance area was approximately 60% compared with that at the minimum luminance area. Accordingly, the GSDF is unsuitable as a calibration tool for the liquid crystal display monitor, which will be used in actual clinical diagnosis, as it cannot achieve 'perceptual linearisation' under the actual environment. For the purpose of clinical diagnosis, it is necessary to enlarge the physical gradient of GSDF further in the high digital driving level range (which relates to a high luminance area) to give an approximation that is as close to the idealised form as possible.

Calibration↗

Ileocolonic lymphomas: a series of 16 cases.

BACKGROUND: Colonoscopic and clinical differences between primary ileocolonic mucosa-associated lymphoid tissue (MALT) lymphoma and mantle cell lymphoma (MCL) have not been defined. METHODS: We reviewed colonoscopic and clinical features in eight patients with primary MALT lymphoma and eight patients with MCL in the terminal ileum and/or colorectum. All cases were examined for CD5 and/or cyclin D1 expression. RESULTS: Endoscopic features of MALT lymphoma were characterized as protrusions that were covered with normal-appearing mucosa with or without ulceration. The gross appearances of MALT lymphomas were categorized as solitary (4 patients), multiple (3 patients), and multiple lymphomatous polyposis (MLP) (1 patient). The gross features of MCL at endoscopy were categorized as multiple protrusions (2 patients), and MLP (6 patients). The clinical stages of patients with MCL were more advanced than in patients with MALT lymphoma. CONCLUSIONS: Solitary or multiple protrusions at an early clinical stage is the most common presentation pattern of patients with MALT lymphoma, but an MLP appearance at an early stage is also possible. On the other hand, MLP appearance with an advanced clinical stage is the main presentation pattern in patients with MCL, although multiple protrusions with an early clinical stage is also possible. Histological and immunohistochemical investigation including that of cyclin D1 and CD5 expression is essential to make the final diagnosis.

Adult↗