Biomedical subjects

K Araki

Publications and source records attributed to K Araki.

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↗

PubMed1997

Targeted integration of DNA using mutant lox sites in embryonic stem cells.

Site-directed DNA integration has been achieved by using a pair of mutant lox sites, a right element (RE) mutant lox site and a left element (LE) mutant lox site [Albertet al. (1995)Plant J., 7, 649-659], in mouse embryonic stem (ES) cells. We established ES cell lines carrying a single copy of the wild-type lox Por LE mutant lox site as a target and examined the frequency of site-specific integration of a targeting vector carrying a loxP or RE mutant lox site induced by Cre transient expression. Since our targeting vector contains a complete neo gene, random integrants can form colonies as in the case of a gene targeting event through homologous recombination. With our system, the frequency of site-specific integration via the mutant lox sites reached a maximum of 16%. In contrast, the wild-type loxP sites yielded very low frequencies (<0.5%) of site-specific integration events. This mutatedloxsystem will be useful for 'knock-in' integration of DNA in ES cells.

Animals↗

PubMed1997

Reliability of ultrasonography and sialography in the diagnosis of Sjögren's syndrome.

OBJECTIVE: The purpose of this study was to evaluate quantitatively observer performance with ultrasonography and sialography in the diagnosis of parotid gland involvement of Sjögren's syndrome. STUDY DESIGN: Sixty-four parotid gland sialograms and 65 ultrasonograms were prepared for observer performance experiments. They included both modalities in 24 Sjögren's syndrome and 19 nonspecific parotitis cases, 21 normal parotid gland sialograms, and 22 normal ultrasonograms in healthy volunteers. The images were randomly sequenced and presented to five observers who were asked to describe several findings and finally to determine the imaging diagnosis by ranking the abnormal features and the diagnosis on a five-point-rating scale. Observer performance was evaluated on the basis of the reliability of findings interpreted and the diagnostic accuracy of each modality from observers' rating scores. RESULTS: The diagnostic accuracy of sialography was very high, nearly perfect. The diagnostic accuracy of ultrasonography was lower than that of sialography, resulting from the lower incidence of characteristic findings in the disease groups and lower sensitivity on ultrasonography. In the differentiation of Sjögren's syndrome from the normal, however, the diagnostic accuracy of ultrasonography increased to 80% for all cases, and up to nearly 90% in the advanced sialographic stages. CONCLUSION: Ultrasonography is useful for the diagnosis of Sjögren's syndrome in the advanced stages. Taking the noninvasiveness of this technique into account we recommend first applying ultrasonography to the diagnosis of Sjögren's syndrome and performing sialography when no positive findings are detected on ultrasonography.

Analysis of Variance↗

PubMed1997

Cytotoxic glycosides from Albizia julibrissin.

During the course of a study of leguminous plants, cytotoxicity was demonstrated by the crude saponin fraction of Albizia julibrissin. Following chromatographic purification, the structures of three novel saponins, julibrosides I-III (1-3), inclusive of a cytotoxic principle, were elucidated. A comparison of the cytotoxicity of julibrosides (1-3) and their prosapogenins (4-15) prepared by alkaline hydrolysis clearly indicated that both an alpha-L-arabinofuranosyl-(1-->4)-[beta-D-glucopyranosyl-(1-->3)]-alpha- L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester unit and a monoterpene-quinovopyranosyl moiety are crucial substituents for cytotoxicity among this class of compounds. The hydroxy group at C-16 of aglycon may play an important role in mediating cytotoxicity, and the N-acetyl-glucosamine moiety at C-3 seems to enhance activity because 3 showed the strongest cytotoxicity.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Species-dependent migration of fish hatching gland cells that express astacin-like proteases in common [corrected].

Two constituent proteases of the hatching enzyme of the medaka (Oryzias latipes), choriolysin H (HCE) and choriolysin L (LCE), belong to the astacin protease family. Astacin family proteases have a consensus amino acid sequence of HExxHxxGFxHExxRxDR motif in their active site region. In addition, HCE and LCE have a consensus sequence, SIMHYGR, in the downstream of the active site. Oligonucleotide primers were constructed that corresponded to the above-mentioned amino acid sequences and polymerase chain reactions were performed in zebrafish (Brachydanio rerio) and masu salmon (Oncorynchus masou) embryos. Using the amplified fragments as probes, two full-length cDNA were isolated from each cDNA library of the zebrafish and the masu salmon. The predicted amino acid sequences of the cDNA were similar to that of the medaka enzymes, more similar to HCE than to LCE, and it was conjectured that hatching enzymes of zebrafish and masu salmon also belonged to the astacin protease family. The final location of hatching gland cells in the three fish species: medaka, zebrafish and masu salmon, is different. The hatching gland cells of medaka are finally located in the epithelium of the pharyngeal cavity, those of zebrafish are in the epidermis of the yolk sac, and those of masu salmon are both in the epithelium of the pharyngeal cavity and the lateral epidermis of the head. However, in the present study, it was found that the hatching gland cells of zebrafish and masu salmon originated from the anterior end of the hypoblast, the Polster, as did those of medaka by in situ hybridization. It was clarified, therefore, that such difference in the final location of hatching gland cells among these species resulted from the difference in the migratory route of the hatching gland cells after the Polster region.

Amino Acid Sequence↗

PubMed1997

Effects of self washout structure on the antithrombogenicity and the hemolytic properties of a centrifugal pump.

Antithrombogenicity in an initial type (N1) of a centrifugal pump (CP) developed in our institute is provided by the central balancing hole of an impeller. A new CP (N2) was modified to obtain better antithrombogenicity, in which the balancing hole was widened to improve self washout flow velocity (Vsf), and an edge of the thrust bearing was rounded off to minimize flow separation. Effects of the modifications were assessed in vitro and in vivo studies. The Vsf of the N1 and the N2 evaluated by a Doppler velocimeter were 12.8 and 22.1 cm/s, respectively. Flow around the thrust bearing, which was visualized by a light cutting method, confirmed less flow stagnation in the N2. The hemolytic indices of the N1 and the N2 were 0.023 and 0.008 mg/dl, respectively. In vivo antithrombogenicity and the hemolytic properties of the N2 and the N1 were investigated without anticoagulation therapy in 3 goats. In each goat the N2 was driven for 1 week and exchanged for the N1, which was driven for the same period. Red thrombi at the thrust bearing were found in 2 N1s, and 2 small thrombi were on the impeller of another N1, whereas a thrombus of less than 1 mm3 at the TB was noted in 1 N2. Plasma free hemoglobin was not increased in either CP. These results indicate that the N2 has better antithrombogenicity and hemolytic properties than the N1.

Animals↗

PubMed1997

[Surgical treatment of aortic valve regurgitation due to nonpenetrating trauma of the chest--a case report and review of the literature in Japan].

A case report and a literature review of the patients in Japan who underwent surgical treatment of an aortic valve regurgitation due to nonpenetrating chest trauma are presented. A 70-year-old man was admitted to our hospital with multiple trauma, including fracture of sternum, caused by traffic accident. After treatment of respiratory and circulatory failure, he was found to have aortic regurgitation and subsequent congestive heart failure. The aortic valve replacement was performed and his postoperative course was good. The tear of aortic valve was detected in the noncoronary cusp, and the size of the tear was 4 mm. The aortic valve was not recognized the findings of inflammatory or rheumatic changes. Before this case, 15 cases were operated in Japan with the diagnosis of traumatic aortic regurgitation. We reviewed them in the table.

Accidents, Traffic↗

PubMed1997

[A study on the quantitative evaluation method of human alertness and its application].

This article presents an alertness evaluation method being analyzed by the authors, and discusses its application. With the aim of quantifying the physiological activity of the living body, the alpha-attenuation test (AAT) for evaluation of alertness was assessed. AAT is a method of quantitatively determining alertness level from alpha-wave power spectra during eye closure and opening. 1. The potential for quantification of diurnal change of alertness by the use of the AAT is suggested. Also rated, are a performance evaluation method based on reaction time and target tracking error and a subjective feeling evaluation method using an analog scale on a computer display. Using these methods of evaluation, measurements were made in 9 healthy men and women at 2-hour intervals over the period from 09: 30 to 19: 30. The findings are summarized as follows: 1) Alertness lowered from 13: 30 to 15: 30, as rated by diurnal change determined by the AAT 2) The performance test and subjective feeling scoring revealed decreased target tracing ability and extended reaction time from 13: 30 to 15: 30, accompanied by reduced performance, increased sleepiness, and failure to achieve accurate, quick action. 2. The relation between the quality of rest and the alpha-attenuation coefficient (AAC), the quantitative index of the AAT, was rated. There were some statistical significances between the quality of rest and the AAC. These results suggest that the AAC is found applicable to the quantitative assessment of diurnal changes of physiological activity, and that the AAC is reflected in the quality of rest.

Adult↗

PubMed1997

[A case of successful surgical treatment for active endocarditis 2 days after the onset of cerebral infarction].

We performed double valve replacement for a patient with active endocarditis 2 days after the onset of cerebral infarction because of intractable cardiac failure. The use of heparin and the hypotension brought by cardiopulmonary bypass can lead exacerbation of the cerebral symptoms after open heart surgery which is performed during acute phase of cerebral infarction. Perfusion pressure was maintained over 70 mmHg during cardiopulmonary bypass and activated clotting time was kept about 400 seconds to prevent aggravation of cerebral complications in this case. The patients recovered from surgery uneventfully. We described a case who was received double valve replacement 2 days after the onset of cerebral infarction successfully.

Aortic Valve↗

PubMed1996

Comparison of mutagenic activity of bile between Chilean and Japanese female patients having cholelithiasis.

The mutagenic activity of bile was compared between Chilean and Japanese female patients having cholelithiasis by the Ames assay using Salmonella typhimurium tester strain TA98 in the presence of S9 mix with blue rayon adsorption technique. A reason for conducting the present investigation is that Chile and Japan have the highest mortality rates for the gallbladder cancer (GBC) in the world. Of 24 bile samples collected in Chile, 20 (83.3%) samples showed mutagenicity. In the case of Japanese bile, 21 (80.8%) of 26 and 5 (19.2%) of 26 cases were mutagenic in samples from high- and low-risk areas for GBC, respectively. Therefore, both the Chilean and the Japanese samples collected in high-risk areas showed higher mutagenic rates than the Japanese ones in a low-risk area, with a statistical significance (p < 0.001), chi-square test). The average number of revertant colonies were 128 +/- 92 (mean +/- SD), 62 +/- 14 and 66 +/- 13, respectively, when the blue rayon extracts of 200 microliters bile were applied to the Ames test. Thus, Chilean bile had a tendency to show a higher mutagenic activity than Japanese.

Adult↗

PubMed1996

E-selectin binding promotes neutrophil activation in vivo in E-selectin transgenic mice.

E-selectin is a membrane protein expressed by endothelial cells activated by cytokines released during the inflammatory process; it plays an important role in neutrophil emigration into inflamed tissues. To further explore in vivo the function of E-selectin, we have generated transgenic mouse line expressing E-selectin under the control of a chicken beta-actin promoter. In these mice, the number of blood neutrophils was reduced, without any other obvious phenotype or tissue damage. These neutrophils, however, displayed two significant changes: first, an alteration in the levels of expression of two membrane receptors involved in neutrophil adhesion to endothelial cells, namely a marked increased in the Mac-1 antigen (CD11b/CD18) and a decrease in the Mel-14 antigen (L-selectin); second, an increased oxidative activity when compared to blood neutrophils of non-transgenic mice, as shown by their capacity to oxidize 2',7'-dichlorofluorescein (DCFH) into a fluorescent compound. These observations indicate that the binding of E-selection with neutrophils bearing its ligands promotes neutrophil activation in vivo.

Actins↗

PubMed1996

An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support.

SUMMARY: An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.

Adult↗

PubMed1996

Redirection of tumor metastasis by expression of E-selectin in vivo.

The selectin class of adhesion molecules plays a critical role in facilitating leukocyte adhesion to and subsequent transmigration of endothelium. On this basis, selectins have been suggested to promote tumor cell attachment to endothelium, thereby facilitating metastasis of certain types of tumors, although direct evidence for such a role is lacking. To explore this hypothesis, two sets of transgenic mice were developed: TgnES, which constitutively expresses cell surface E-selectin in all tissues, under the control of the beta-actin promoter; and TgnEsol, which expresses truncated, soluble E-selectin in the liver, under the control of the alpha 1 antitrypsin promoter. B16F10 melanoma cells were stably transfected with alpha(1,3/1,4) fucosyltransferase-specific cDNA (B16F10ft), allowing them to express E-selectin ligands or with hygromycin resistance selection vector only B16F10hygro). Normal mice injected with B16F10ft and B16F10hygro and transgenic mice injected with B16F10hygro developed lung tumors exclusively. In contrast, TgnES mice injected with B16F10ft cells developed massive infiltrating liver tumors. B16F10ft cells injected into TgnEsol mice also formed liver tumors, but these grew more slowly, with a well-delineated, noninfiltrating distinct histologic pattern. These observations provide direct evidence that expression of E-selectin can redirect metastasis of tumor cells expressing appropriate ligands in vivo.

Animals↗

PubMed1996

Two families of murine carbohydrate ligands for E-selectin.

In search of endogenous oligosaccharide ligands for the endothelial adhesion molecule E-selectin in mouse, glycolipids from tissues and the neutrophilic cell line 32D c13 were tested for E-selectin binding. Kidneys of BALB/c and NMRI mice (but not CBA) and the 32D c13 cells were found to contain minor glycolipid populations that support strongly the binding of murine E-selectin. By chromatogram binding experiments and in situ liquid secondary ion mass spectrometry (LSIMS) with neoglycolipids derived from their endoglycoceramidase-released oligosaccharides, in conjunction with compositional and linkage analyses, one of the glycolipid ligands in kidney was identified as the Le(x)-active extended globo-glycolipid: [formula: see text] Neoglycolipids enriched for the ligand structures were obtained from oligosaccharides released by endo-beta-galactosidase from the 32D c13 cells. By TLC-LSIMS and antibody binding, the main E-selectin binding determinant on these was identified as sialyl-Le(a).

Animals↗

PubMed1996

Prevention of murine lupus by an I-E alpha chain transgene: protective role of I-E alpha chain-derived peptides with a high affinity to I-Ab molecules.

The expression of a transgene encoding the I-E alpha chain prevents a lupus-like autoimmune syndrome in BXSB mice. However, it had not been elucidated whether the E alpha d transgene-mediated protective effect results from I-E expression or from the generation of I-E alpha chain-derived peptides (E alpha peptide) displaying high affinity for the I-Ab molecule. To address this question, two different BXSB lines expressing the transgene at low or high levels were crossed with lupus-prone MRL mice; this resulted in three types of (MRL x BXSB)F1 mice, differing in the expression levels of I-E molecules and of E alpha peptides presented by I-Ab molecules. Comparative analysis of these three (MRL x BXSB)F1 mice as well as several BXSB transgenic lines showed that the E alpha d transgene-mediated protection paralleled the expression levels of E alpha peptide presented by I-Ab molecules, but not of I-E molecules on B cells. In addition, use of transgenic and nontransgenic double bone marrow chimeras showed a selective activation of nontransgenic B cells during I-Ab-restricted T cell-dependent immune responses, while both transgenic and nontransgenic B cells were comparably activated during T cell-independent responses. These results favor a model of autoimmunity prevention based on competition for antigen presentation, in which excessive generation of E alpha peptides prevents, because of their high affinity to the I-A molecules, activation of potential autoreactive T and B cells.

Amino Acid Sequence↗

PubMed1996

Diagnostic value of magnetic resonance imaging for malignant tumors in the oral and maxillofacial region.

The purpose of this study was to clarify the diagnostic value of magnetic resonance imaging for malignant tumors in the oral and maxillofacial region. Computed tomography and magnetic resonance images of 25 patients with malignant tumors of the oral and maxillofacial region were evaluated. Computed tomography scans were performed with intravenous contrast enhancement. A 0.2-Tesla (Hitachi Medical Corp., Tokyo, Japan) permanent magnetic resonance unit was used to obtain T1-, T2-, and proton-density-weighted images with spin-echo pulse sequences. Gadolinium-diethylene-triamine-pentaacetic acid was administered in 11 cases. Severe artifacts influencing image interpretation were observed in 10 (40%) cases on computed tomography but only in 5 (20%) cases on magnetic resonance imaging. There was no difference in the detectability of bone invasion between images from the two systems. Contrast enhancement with gadolinium-diethylene-triamine-pentaacetic acid provided additional useful information in only 3 of 11 cases compared with nonenhanced magnetic resonance images. Malignant tumors showed a higher signal intensity than that of muscle on T2-weighted images in all cases and on proton-density-weighted images in 23 (92%) cases. On T1-weighted images, an intermediate signal intensity similar to that of muscle was seen in 16 (64%) cases and a hyperintense signal in 9 (36%) cases. There was poor correlation between signal intensity and pathologic diagnosis of the tumors. These results suggest that in cases with severe artifacts that disturb the interpretation of the images on computed tomography, magnetic resonance examinations are preferable for defining the exact extent of the primary lesion.

Adult↗

PubMed1996

Comparison of mucosal microvasculature between the proximal and distal human colon.

The microcirculation of the human colon with special reference to the differences in microvascular architecture between the proximal and distal colon was studied by scanning electron microscopy with vascular corrosion casting technique. The subsurface capillary networks of the ascending colon were honeycomb-like and multi-layered, with an average number of capillary layers per capillary loop of 3.28 +/- 1.10 (mean +/- SD). Whereas, those of the sigmoid colon were almost single-layered, and the average number of capillary layers was 1.19 +/- 0.39. In the cross-section of vascular casts of both parts of the colon, the ascending capillaries originating from the submucosal arterioles ascended into the mucosal layer and joined into the subsurface capillary networks, which drained into the collecting venules near the surface. The mean diameter of the collecting venules of the ascending and the sigmoid colon was 29.3 +/- 6.41 microns and 19.48 +/- 2.23 microns, respectively. From these findings, it is speculated that the multi-layered capillary networks of the proximal colon are closely related to the greater water absorption and electrolyte transport activities compared to those of the distal colon.

Aged↗

PubMed1996

Meiotic abnormalities of c-mos knockout mouse oocytes: activation after first meiosis or entrance into third meiotic metaphase.

In Xenopus oocytes, Mos activates the mitogen-activated protein kinase (MAPK) signal transduction cascade and regulates meiosis. In mammalian oocytes, however, the functions of Mos are still unclear. In the present study, we used c-mos knockout mouse oocytes and examined the roles of Mos in mouse oocyte maturation and fertilization, including whether Mos controls MAPK and maturation promoting factor (MPF) activity. The kinetics of germinal vesicle breakdown (GVBD) and the first polar body emission were similar in wild-type, heterozygous mutant, and homozygous mutant mice. Activities of MPF were also not significantly different among the three genotypes until the first polar body emission. In contrast, MAPK activity in c-mos knockout oocytes did not significantly fluctuate throughout maturation, and the oocytes had abnormal diffused spindles and loosely condensed chromosomes, although a clear increase in MAPK activities was observed after GVBD in wild-type and heterozygous mutant oocytes that had normal spindles and chromosomes. After the first polar body emission, 38% of c-mos knockout oocytes formed a pronucleus instead of undergoing second meiosis, indicating the crucial role of Mos in MPF reactivation after first meiosis. When oocytes that reached second metaphase were fertilized or stimulated by ethanol, many c-mos knockout oocytes emitted a second polar body and progressed into third meiotic metaphase instead of interphase, although all fertilized or activated oocytes in the heterozygote progressed to interphase, indicating that Mos deletion leads to compensatory factors that might not be degraded after fertilization or parthenogenetic activation. These results suggest that Mos is located upstream of MAPK in mouse oocytes as in Xenopus oocytes but is independent of MPF activity, and that Mos/MAPK is not necessary go GVBD and first polar body emission. Our results also suggest that Mos plays a crucial role in normal spindle and chromosome morphology and the reactivation of MPF after first meiosis.

Animals↗