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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

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

Clonic perseveration in the subacute stage of Japanese encephalitis.

We report a very rare case of Japanese encephalitis (JE) presenting with reversible stereotyped movement in the subacute stage. A 58-year-old woman presented with high fever, headache, nausea, vomiting, and consciousness disturbance. Cranial magnetic resonance imaging (MRI) of fluid attenuated inversion recovery (FLAIR) and T2-weighted image (WI) showed high intensity areas in the bilateral thalamus, caudate nucleus and hippocampus. She developed coma, convulsion, and ballism in the acute stage. One month after onset, she showed rhythmic, stereotyped, repetitive movements with hypoperfusion in the thalamus and frontal cortex on single photon emission computed tomography (SPECT). Three months later, her stereotyped movement improved accompanied by recovery of hypoperfusion in the thalamus and frontal cortex on SPECT. We speculated that her stereotyped movement was clonic perseveration due to frontal dysfunction induced by thalamofrontal disconnection.

Brain↗
PubMed2006

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells.

Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.

Animals↗
PubMed2006

Varicose veins associated with CADASIL result from a novel mutation in the Notch3 gene.

No genetically diagnosed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) pedigrees with venous insufficiency have been described. In a CADASIL pedigree with varicose veins, the authors have identified a novel heterozygous mutation in the 3' splice acceptor site of intron 15 of the Notch3 gene. This, based on mRNA analysis, resulted in skipping of exon 16 including eight cysteine residues of EGF-like repeats.

Adult↗
PubMed2005

Light-scattering study on the shear-orientation coupling of liquids near isotropic-to-nematic phase transition.

Microscopic interaction between the translation and rotation of rodlike molecules yields the shear-orientation coupling in the macroscopic view. The depolarized scattering component arising from orientational fluctuations gives a constant in the strength of the coupling, which is related to the three viscosity parameters introduced by de Gennes. A high-resolution system of light scattering with an improved optical beating method was utilized for measurements in the 4-cyano-4'-alkylbiphenyl nCB series: propyl (3CB), butyl (4CB), pentyl (5CB), hexyl (6CB), heptyl (7CB), and octyl (8CB). All the coupling constants obtained in these samples showed clear dependence on temperature, and their behaviors were interpreted in terms of a critical phenomenon near T*, the virtual isotropic-nematic phase transition point. The values of T* were also given by the light scattering experiment, and the critical exponent of shear-orientation coupling was determined to be 0.31. Furthermore, the characteristic value of the coupling constant was correlated with the aspect ratio of these rodlike molecules, and two clear facts were found: a stronger coupling in longer molecules; and an odd-even effect with respect to the number of C-C bonds in the alkyl chain.

Journal Article↗
PubMed2005

Posttranslational modifications of decidual IGFBP-1 by steroid hormones in vitro.

Insulin-like growth factor binding protein-1 (IGFBP-1) appears to regulate insulin-like growth factors (IGFs; IGF-I and IGF-II) biological activity within the local environment of human placenta by modulating IGFs interaction with their receptors. Considering that posttranslational modifications of IGFBP-1 such as phosphorylation and proteolysis affect its affinity for IGFs, this study was undertaken to identify the role of estrogen and progesterone in this regard. The conditioned media of steroid hormone-treated decidual cells were evaluated using different approaches using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and non-denaturing PAGE following immunoblotting as well as zymographys that contained gelatin and IGFBP-1 as substrates. Our results demonstrated that medroxy progesterone acetate (MPA) treatment increased both phosphorylated and non-phosphorylated decidual-secreted IGFBP-1, whereas 17beta-estradiol (E2) treatment attenuated its phosphorylated forms. Furthermore, the results of zymography revealed that steroid hormones regulated the activity of decidual-secreted matrix metalloproteinases (MMP)-2 and -9, in which E2 treatment up-regulated the MMP-9 activity. Finally, it was demonstrated in our study that decidual-secreted MMP-9 was capable of degrading human amniotic fluid-derived IGFBP-1. In conclusion, our data implicate steroid hormones in the control of IGF system activities at the embryo-maternal interface, at least in part, through their effects on the post-translation changes of decidual-secreted IGFBP-1 such as its phosphorylation and/or proteolysis.

Adult↗
PubMed2005

Kinetic pathway to double-gyroid structure.

We have investigated the structural development during order-order transitions to the double-gyroid (DG) phase of nonionic surfactant/water systems based on two-dimensional small-angle x-ray scattering patterns from highly oriented ordered mesophases. The lamellar (L) to DG transition proceeds through two intermediate structures, a fluctuating perforated layer structure having ABAB stacking and a hexagonal perforated lamellar structure with ABCABC stacking (HPLABC). For a hexagonally packed cylinder (H) to DG transition, we also observed the HPLABC structure as the intermediate phase, thus the HPLABC is an entrance structure for the DG phase. The hexagonal perforated lamellar (HPL) structure consists of hexagonally packed holes surrounded by the planar tripods, and the transition from HPL structure to the DG phase proceeds by rotation of the dihedral angle of connected tripods. A geometrical consideration shows that large deformations of HPL planes are necessary to form the DG structure from the HPLABC structure, whereas the transition from a HPL structure with ABAB stacking (HPLAB) to the DG structure is straightforward. In spite of the topological constraints, the HPLABC structure is observed in the kinetic pathway to the DG structure.

Journal Article↗
PubMed2005

Direct observation of slow molecular relaxation by high-resolution light scattering spectroscopy.

We developed a novel dynamic light scattering system to observe elastic relaxation phenomena with hyper frequency resolution. The principle of the measurement is based on the theory, which describes the dynamic structure factor of fluid under the condition of the frequency dependent compressibility. The dynamic structure factor, which is usually composed of the Brillouin and Rayleigh triplet, is modulated and shows an additional central component that directly reflects the whole aspect of the relaxation. In the experiment, the output from a frequency-doubled cw-YAG laser was incident into the liquid sample and the power spectrum of the light scattered into the backward direction was analyzed by the optical beating spectroscopy technique. The sample is liquid acetic acid that is known to show a strong ultrasonic relaxation around 1 MHz due to the molecular association process. We could find in the observed spectrum, the central component introduced by the phenomenon, whose relaxation frequency and the strength can be obtained from the width and the intensity of the observed central peak, respectively. The results show very good agreement with those previously obtained by the conventional ultrasonic spectroscopy technique.

Journal Article↗
PubMed2005

Evidence for a novel racemization process of an asparaginyl residue in mouse lysozyme under physiological conditions.

We examined chemical reactions in mouse lysozyme after incubation under physiological conditions (pH 7 and 37 degrees C). After incubation for 8 weeks, racemization was observed specifically at Asn127 among the 19 Asp/Asn residues in mouse lysozyme. Furthermore, analysis of the primary structure showed that the racemized residue was not Asp, but Asn, which demonstrates that deamidation and isomerization did not occur. These results mean that this racemization occurs without forming a succinimide intermediate. This is the first example of D-asparaginyl formation in a protein occurring during the racemization process under physiological conditions.

Amino Acid Sequence↗
PubMed2005

Baseline glomerular sclerosis influences morphological changes, but not level of serum creatinine.

The aim of this study was to investigate whether glomerular sclerosis (GS) at the time of engraftment affects subsequent morphology and clinical course of renal allografts. Eighty-one renal transplant recipients were recruited for this study. Protocol biopsies of the renal allografts were performed at engraftment, as well as at 1, 3, 5, and 7 years after transplantation. All cases were divided into 2 groups based on the presence of GS at engraftment, namely, non-GS and GS groups. Morphological changes in the renal allografts were graded from 0 to 3+ based on the severity of chronic allograft nephropathy (CAN) of the Banff classification based on 5 factors: percentage of GS, extent of interstitial fibrosis, tubular atrophy, arterial intimal thickening, and arteriolar hyalinosis. Furthermore, the level of serum creatinine (s-Cr) at each year was examined by recipient age and gender, donor age and gender, type of donor (living/cadaver), delayed graft function, acute rejection within 1 year after transplantation, mean blood pressure, and use of calcineurin inhibitors as well as the presence of GS at engraftment. The extent of GS at engraftment significantly correlated with donor age (P = .0038) but with a weak correlation coefficient. Although the severity of CAN developed gradually in both non-GS and GS groups, differences in morphological changes at engraftment between the 2 groups persisted throughout 7 years. Donor age and recipient gender influenced s-Cr significantly. In conclusion, the presence of GS at engraftment aggravates subsequent morphological changes and affects short-term but not long-term allograft prognosis.

Adolescent↗
PubMed2005

The pathologic impact of tacrolimus on protocol biopsy in renal transplant patients with basiliximab-based immunosuppression.

Forty-two ESRD patients underwent renal transplantation using basiliximab (mean age: 30.6 +/- 18.6 years at transplantation; male: 50%; ESRD duration: 51.6 +/- 13.0 months) between February, 2000 and July, 2003. All patients had a protocol biopsy on the day of transplant, on discharge from the hospital (35.5 +/- 13.2 days), and at 1 year after transplant. The immunosuppression included a calcineurin inhibitor, basiliximab, mycophenolate mofetil (MMF), and methylprednisolone. While 16 patients used tacrolimus (FK group: 29.4 +/- 16.6 years old), 26 patients used cyclosporine (CsA group: 31.4 +/- 20.1 years old). Protocol biopsies were graded according to the Banff 97 classification. The incidence of acute rejection episodes within 1 year was greater in the CsA (15%) than the FK group (6%). Serum creatinine at hospital discharge was similar (CsA: 1.01 +/- 0.59 mg/dL, FK: 0.97 +/- 0.49, p = .18); however creatinine at 1 year differed significantly (CyA: 1.22 +/- 0.88 mg/dL, FK: 0.92 +/- 0.39, P = .03). There was a trend toward an increase in the score of interstitial inflammations in the CsA group, while it remained constant in the FK cohort (P = .05 at 1 year between the two groups). Other pathologic scores (t, ci, ct, cv, ah) did not differ between the groups at 1 year. Although there were no differences in the demographics between the two groups, there were several trends toward better renal function in the FK group.

Antibodies, Monoclonal↗
PubMed2005

Importance of early repair of isolated abdominal aortic dissecting aneurysm.

BACKGROUND: Since the available information on isolated abdominal aortic dissecting aneurysm (AADA) is mainly related to case reports or reports of small groups of patients, its natural history remains undetermined and there is no agreement on its optimal management. The purpose of this study is to define the features and pattern of development of this unusual entity as well as to propose criteria for treatment based on our own experience and previously published data. PATIENTS AND METHODS: We retrospectively evaluated the history of 6 patients diagnosed with AADA. The patients were 5 males and 1 female. The mean age was 71 +/- 8 years (range: 61-80 years), and the mean aneurysm diameter was 54 +/- 14 mm (range: 35-70 mm). All of these patients were hypertensive (100%). History of cerebrovascular accident, ischemic heart disease, peripheral arterial disease, or diabetes mellitus was present in 1 patient, respectively. Two patients developed mycotic AADA. RESULTS: Emergency operations had been performed in 3 cases, and scheduled surgical reconstruction in the remaining 3 cases. Operation consisted of aneurysmectomy and graft replacement of the diseased aortic segment in all cases. One patient treated in an emergency setting died subsequently of multisystem organ failure, but the others did well. CONCLUSION: Symptomatic patients or patients at good risk should undergo surgical repair earlier than in the case of abdominal aortic aneurysm without dissection (AAA). Dissection in addition to an AAA will further increase the weakness of the aortic wall and the possibility of aortic rupture will become higher.

Aged↗
PubMed2005

The "pulvinar sign" in a case of paraneoplastic limbic encephalitis associated with non-Hodgkin's lymphoma.

This paper reports a 59 year old woman with paraneoplastic limbic encephalitis associated with diffuse large B cell lymphoma. Her brain magnetic resonance imaging scan showed bilateral posterior thalamic hyperintensities, similar to the "pulvinar sign". Her symptoms included progressive psychiatric disturbance and resembled the initial symptoms of variant Creutzfeldt-Jakob disease (vCJD). Clinicians should consider this treatable disorder in the differential diagnosis of vCJD.

Axilla↗
PubMed2005

Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice.

T-helper cell type 1 (Th1) cells have been postulated to have a significant role in protective immunity against allergic diseases. However, recent studies using polarised Th1 cells showed conflicting effects on both airway responsiveness and eosinophilic inflammation in a mouse asthma model. The current study explored the effects of adoptive transfer of established Th1 clones on a murine model of atopic asthma. Mice (BALB/c) were sensitised with ovalbumin (OVA) and challenged with aerosolised OVA (5%, 20 min) for 5 days. Just before starting the first challenge, Th1 clones (5x10(6) x body(-1)) or PBS alone were injected via the tail vein. After assessment of airway responsiveness to methacholine, bronchoalveolar lavage fluid (BALF) was obtained. Histological examination, including morphometric analysis, measurement of cytokines in the BALF and Northern blotting of lung chemokines, was also performed. Adoptive transfer of Th1 clones showed a significantly increased total number of cells, whereas significantly decreased eosinophils were found in the BALF, when compared with mice with injection of vehicle alone or splenic mononuclear cells. Administration of Th1 clones significantly decreased the infiltration of eosinophils but increased mononuclear cells in the peribronchial area. Goblet cell hyperplasia and peribronchial fibrosis were also suppressed by Th1 clones. The transfer of Th1 cells significantly decreased airway responsiveness. Th1 injection significantly increased interferon gamma in the BALF, but significantly decreased interleukin (IL)-5 and IL-13. Eotaxin mRNA was predominantly expressed in the lungs of asthma model mice, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) predominates in such mice with Th1 transfer. In conclusion, results suggest that the adoptive transfer of T-helper cell type 1 clones can suppress both lung eosinophilia and airway responsiveness, but increase noneosinophilic inflammation in a mouse model of asthma.

Adoptive Transfer↗
PubMed2004

Production of L-lactic acid from a mixture of xylose and glucose by co-cultivation of lactic acid bacteria.

The production of optically pure lactic acid in a high yield from xylose or a mixture of xylose and glucose, which is a model hydrolysate of lignocellulose, is described. In a single cultivation, Enterococcus casseliflavus produced 38 g/l of lactic acid with an optical purity of 96% enantiomeric excess (ee) and 6.4 g/l of acetic acid from 50 g/l of xylose when MRS medium was used. When a mixture of 50 g/l of xylose and 100 g/l of glucose was used as the carbon source in a cultivation of E. casseliflavus alone, glucose was converted to lactic acid in the early phase of the cultivation but xylose was hardly consumed. In a co-cultivation where E. casseliflavus and Lactobacillus casei specific for glucose were simultaneously inoculated, little or no lactic acid was produced after the glucose was almost consumed. A co-cultivation with two-stage inoculation (in which E. casseliflavus was added at a cultivation time of 40 h after L. casei cells were inoculated) resulted in complete consumption of 50 g/l of xylose and 100 g/l of glucose. In the co-cultivation, 95 g/l of lactic acid with a high optical purity of 96% ee was obtained at 192 h. Such a co-cultivation using two microorganisms specific for each sugar is considered to be one promising cultivation technique for the efficient production of lactic acid from a sugar mixture derived from lignocellulose.

Coculture Techniques↗