PubMed Health⌕ Search

Biomedical subjects

H Kajiyama

Publications and source records attributed to H Kajiyama.

At least 19 recordsLinked to original sources
PubMed2007

Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients.

Twist is a transcription factor that regulates the expression of tumour suppressors such as E-cadherin. We examined the distribution and expression of Twist in human epithelial ovarian carcinoma (EOC) to examine its clinical significance. Paraffin sections from EOC tissues (n=82) were immunostained with Twist antibody, and the staining intensity was evaluated. The clinicopathological factors examined were age, International Federation of Gynecology and Obstetrics staging, histological type, tumour grade, preoperative value of CA125, peritoneal cytology, volume of ascites and residual tumour after cytoreductive surgery. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Of the 82 carcinomas, 49 (59.8%) cases were negative for Twist immunoexpression, and 33 (40.2%) were positive immunoexpression. When categorized into negative vs positive expression, Twist was not associated with any of the clinicopathological parameters examined. However, positive Twist expression significantly predicted poorer OS and PFS when compared with negative expression (P<0.0001). In the multivariate analyses, positive Twist expression was the only independent prognostic factor for survival in this study (P<0.0001). Positive Twist expression seems to be a useful marker in patients with EOC likely to have an unfavourable clinical outcome.

Blotting, Western↗
PubMed2006

Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. The present study aimed to investigate IDO expression and its prognostic significance in endometrial cancer. Indoleamine 2,3-dioxygenase expression in endometrial cancer tissues (n = 80) was immunohistochemically scored as four groups (IDO-, 1+, 2+, and 3+). The high IDO expression (IDO2+ or 3+) in tumour cells was found in 37 (46.3%) of the 80 cases, and was positively correlated with surgical stage, myometrial invasion, lymph-vascular space involvement, and lymph node metastasis, but not with the histological grade. Patients with high IDO expression had significantly impaired overall survival and progression-free survival (PFS) (P = 0.002 and P = 0.001, respectively) compared to patients with no or weak expression of IDO (IDO- or 1+). The 5-year PFS for IDO-/1+, 2+, and 3+ were 97.7, 72.9, and 36.4%, respectively. Even in patients with early-stage disease (International Federation of Gynecology and Obstetrics I/II, n = 64), the PFS for IDO2+/3+ was significantly poor (P = 0.001) compared to that for IDO-/1+. On multivariate analysis, IDO expression was an independent prognostic factor for PFS (P = 0.020). These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.

Biomarkers, Tumor↗
PubMed2006

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival.

Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT(1)R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT1R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT1R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n = 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT1R, the overall survival and progression-free survival were significantly poor (P = 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT1R, although VEGF, but not AT1R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT1R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.

Disease Progression↗
PubMed2005

Angiotensin II augmented migration and invasion of choriocarcinoma cells involves PI3K activation through the AT1 receptor.

While angiotensin II (Ang II) has been shown to inhibit migration of extravillous trophoblasts via plasminogen activator inhibitor-1 (PAI-1) activation, it has remained unclear whether it stimulates or inhibits malignant behavior of choriocarcinoma cells. Since we previously found an involvement of the renin-angiotensin system (RAS) in the proliferative potential in choriocarcinoma cells (BeWo), mediated via the Ang II type 1 receptor (AT1R), in the present study we investigated the effects of Ang II on choriocarcinoma cell migration/invasion in vitro using Transwell cell culture chambers. Ang II (10(-8)M) promoted migration and invasion by a choriocarcinoma cell line and augmented random cell mobility on checkerboard analysis. Immunoblotting showed Ang II to activate the phosphorylation of FAK and Akt in BeWo cells. Furthermore Ang II effects on cell migration were abolished by a selective AT1R antagonist and a phosphatidylinositol 3-kinase (PI3K) inhibitor. The present results suggest that Ang II-induced migration and invasion of choriocarcinoma cells probably involves PI3K following binding to the AT1R.

Angiotensin II↗
PubMed2005

Changes in placental dipeptidyl peptidase IV in preeclampsia with intrauterine growth restriction.

The purpose of this study was to examine alterations in placental expression of dipeptidyl peptidase IV (DPPIV). The localization of DPPIV was compared in control and preeclamptic placentas. Enzyme activity, mRNA, and protein expression were also measured. In term placentas, DPPIV was expressed preferentially in the fetal vascular endothelial cells within stem villi and only weakly in the villous stromal cells. DPPIV activity in control placentas showed no remarkable changes throughout gestation. Levels of activity in samples from normotensive control cases and women having preeclampsia with or without intrauterine growth restriction were 11.8 +/- 2.1, 13.4 +/- 1.1, and 15.3 +/- 0.62 pmol pNA/min/mg protein, respectively. The preeclamptic placentas with intrauterine growth restriction thus showed significantly higher levels of activity than the controls (p < 0.05). We propose that placental DPPIV influences fetal metabolism via the degradation of fetoplacental circulating bioactive peptides, including incretins, resulting in the regulation of fetal growth.

Adult↗
PubMed2003

Dopant-pair structures segregated on a hydrogen-terminated Si(100) surface.

Novel atomic structures on a H-terminated Si(100)-(2x1)-H surface were found using scanning tunneling microscopy (STM). The structures are distinguishable only from Si dimers in empty-state STM images. They were observed on arsenic- and phosphorus-doped substrates, but not on boron-doped substrates. Surface density of these structures was found to be proportional to the dopant density in the substrate. First-principles calculations clarify that they are consisting of dopant pairs that are segregated from the bulk material. Hydrogen atoms attached to the dopant pair are found to flip between two positions on the surface due to a quantum effect.

Journal Article↗
PubMed2003

Doppler flow and arterial location in ovarian tumors.

OBJECTIVES: This prospective study investigated the clinical evaluation of transvaginal color Doppler ultrasonography in the diagnosis of ovarian tumors. METHODS: Transvaginal ultrasonography (morphological assessment, DePriest's index) and color Doppler analysis were performed for 31 malignant and 64 benign tumors ovarian tumors. Serum tumor markers such as CA125, CA72-4, and STN were measured. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were as follows: DePriest's index, 90.3%, 73.4%, 62.2%, 94.0%, 78.9%; CA125, 70.4%, 87.7%, 73.1%, 86.2%, 82.1%; minimum pulsatile index combined with detection of location of arterial blood flow, 83.9%, 98.4%, 96.3%, 92.6%, 93.7%, respectively. In cases where arterial blood flow was recognized, malignant tumors had significantly fewer diastolic notches, while benign tumors had many diastolic notches. The difference in the presence of diastolic notch between malignant and benign tumors was significant (P<0.0004). CONCLUSIONS: For diagnosis of ovarian tumors, transvaginal color Doppler analysis combined with detection of arterial location is more useful than other procedures.

Adult↗
PubMed2002

Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation.

The presence of an extrahypothalamic gonadotropin releasing hormone (GnRH) in human placenta is well known and this decapeptide is presumed to play an important role in the regulation of the function and growth of human placenta. Immunohistochemistry showed that neutral endopeptidase 24.11 (NEP), a candidate of the responsible enzyme of GnRH degradation, is highly expressed on the cell surface of trophoblasts. Hydrolysis of GnRH by human villi was studied by measuring liberated amino acids using high performance liquid chromatography. The GnRH degrading activity was 1.53 times higher after incubation with the membrane fraction of first trimester villi than that after incubation with the membrane fraction of term villi. Phosphoramidon, a potent inhibitor of NEP, reduced the liberated amino acids to about a half, suggesting that NEP is a responsible enzyme for GnRH degradation. Ubenimex, which can inhibit several aminopeptidases, also reduced the liberated amino acids to about 50 per cent. O-phenanthroline, EDTA, and thiorphan could inhibit GnRH degradation but inhibitors of post proline endopeptidase could not. Furthermore, GnRH degrading activity of the membrane fraction was reduced remarkably after the membrane fraction was immunotitrated by anti NEP and anti placental leucine aminopeptidase (P-LAP) IgG. In conclusion, NEP and P-LAP are responsible enzymes for GnRH degradation in human villi.

Adult↗
PubMed2002

Neutral endopeptidase/CD10 expression during phorbol ester-induced differentiation of choriocarcinoma cells through the protein kinase C- and extracellular signal-regulated kinase-dependent signalling pathway.

Neutral endopeptidase 24.11 (NEP) is identical to CD10, which is a differentiation antigen for early B-lymphoid progenitors in the B-cell differentiation pathway. This ectoenzyme is known to have a key role in the control of growth, differentiation, and signal transduction of many cellular systems by regulating bioactive peptides and cytokines. Recently, we demonstrated that NEP/CD10 is upregulated during forskolin-induced choriocarcinoma cell differentiation, suggesting that NEP/CD10 is a trophoblast differentiation marker. The purpose of this study was to clarify the enhancement of NEP/CD10 expression and its signal transduction pathway during phorbol ester (PMA)-induced differentiation of BeWo choriocarcinoma cells. PMA-induced differentiation of BeWo cells was confirmed by morphological change and human chorionic gonadotropin (hCG) secretion, which was completely blocked by a protein kinase C (PKC) inhibitor, Bisindolylmaleimide I (Bis I). On immunoblot analysis, PMA enhanced NEP/CD10 expression in a dose- and time-dependent manner, which was completely abolished by Bis I and a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor, PD98059. PMA also induced phosphorylation of p44/p42 extracellular signal-regulated kinases (ERK) 1 and 2. These observations indicated that activation of PKC by PMA induced differentiation of BeWo cells, and that PMA activated MAPK/ERK, which resulted in the enhancement of NEP/CD10 expression. Furthermore, immunocytochemical analysis showed that NEP/CD10 expression was detected on the membranes of PMA-treated differentiated BeWo cells. In summary, we demonstrated that NEP/CD10 was enhanced during PMA-induced differentiation of BeWo choriocarcinoma cells through a PKC-dependent MEK/ERK signalling pathway. Our findings also suggest that NEP/CD10 may play a functional role in the process of trophoblast differentiation.

Antigens, Differentiation↗
PubMed2002

Increased expression of dipeptidyl peptidase IV in human mesothelial cells by malignant ascites from ovarian carcinoma patients.

Cell surface aminopeptidases play an important role in biological processes through degradation of small peptides. There are many bioactive peptides in ascites and these peptides are involved in carcinoma cell dissemination and infiltration. In human mesothelial cells dipeptidyl peptidase IV (DPPIV) shows the highest expression mostly in four cell surface aminopeptidases: aminopeptidase A, neutral endopeptidase 24-11, aminopeptidase N and DPPIV. Since mesothelial cells are always in contact with ascites, we examined the influence of malignant ascites on DPPIV. DPPIV enzyme activity in mesothelial cells was enhanced by the addition of ascites obtained from ovarian carcinoma patients in a time- and concentration-dependent manner, and flow cytometry and immunocytochemistry also revealed an increased expression of DPPIV on the cell surface of mesothelial cells. The <3-kD fraction of malignant ascites increased the DPPIV enzyme activity to the same level as the total ascites. Northern hybridization demonstrated that DPPIV mRNA was increased 3-fold by the addition of the <3-kD malignant ascites. In conclusion, DPPIV is highly expressed in human mesothelial cells and was regulated by ascites.

Aminopeptidases↗
PubMed2001

Atomic wire oxidation of H-terminated Si(100)-( 2x1): domino reaction via oxidation and H migration.

We studied oxidation at a dangling bond (DB) on the H-terminated Si(100) surface by the first-principles calculations. We found that oxidation easily occurs at the exposed DB on the H-terminated Si(100) surface. The dissociated O atoms are chemisorbed at a dimer bond and a back bond, resulting in adjacent H atom migration onto the DB. As a consequence of the alternate oxidation and subsequent H atom migration processes, the atomic wire oxidation is actually found to occur on the H-terminated Si(100) surface at low temperatures without desorbing H atoms, as observed in our scanning tunneling microscopy experiment.

Journal Article↗
PubMed2001

A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis.

OBJECTIVE: To address whether the gamma haplotype at exon 3 of the SAA1 gene is directly associated with type AA amyloidosis or is merely in linkage with an unknown polymorphism that is primarily associated with disease risk, we examined the SAA1 gene for new polymorphisms. METHODS: We analyzed DNA samples from 44 rheumatoid arthritis (RA) patients with AA amyloidosis (amyloid group), 55 RA patients without AA amyloidosis (RA group), and 58 non-RA healthy subjects (non-RA group). We also examined DNA samples from 50 Caucasians to compare linkage disequilibrium relationships involving SAA1 region polymorphisms between Japanese and Caucasoid populations. RESULTS: We observed 3 novel single-nucleotide polymorphisms (SNPs) in the 5'-flanking region of SAA1: -61C/G, -13T/C, and -2G/A. Comparison of allele frequencies and ratios of individuals with particular alleles between the study groups revealed statistically significant differences between the amyloid and RA groups and between the amyloid and non-RA groups. Statistical analysis revealed that the -13T/C SNP was strongly associated with AA amyloidosis. In addition, we found tight linkage between the -13T allele and the alpha haplotype, rather than the beta haplotype, at exon 3 in the Caucasoid population, while -13T was closely linked to the gamma and beta haplotypes, rather than the alpha haplotype, in the Japanese population. Since the linkage disequilibrium relationship was reversed between the Japanese and Caucasoid populations, different exon 3 haplotypes of SAA1 are found to be associated with the risk of AA amyloidosis in different ethnic groups. CONCLUSION: Our data suggest that the SAA1 -13T allele, rather than SAA1 exon 3 haplotypes, is primarily associated with AA amyloidosis risk.

Amyloidosis↗
PubMed2001

Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells.

Neutral endopeptidase (NEP)/CD10, a cell-surface peptidase degrading various bioactive peptides, is mainly present in syncytiotrophoblasts in the human placenta. However, the change in NEP expression upon trophoblast differentiation remains to be clarified. In the present study, we examined the expression of NEP in the differentiating trophoblast using the BeWo choriocarcinoma cell line as a model system. Under the normal culture conditions, NEP was very weakly expressed on most proliferating cytotrophoblastic BeWo cells, while a minority of the cell population (less than 5 per cent ), consisting of giant, multinucleated cells, clearly expressed NEP at the cell membrane. Treatment of BeWo cells with forskolin (FSK) for 48-72 h resulted in an 11- to 44-fold increase in the level of hCG secretion and induced cell fusion leading to the formation of multinucleated syncytiotrophoblasts, indicating functional and morphological differentiation. Fluorescence-activated cell sorting (FACS) analysis revealed that treatment with FSK significantly increased the cell-surface protein expression of NEP on differentiating BeWo cells. Consistently, there was a significant increase in the NEP enzymatic activity after FSK treatment. The level of hCG secretion from the FSK-treated cells was further enhanced when the cells were treated in the presence of the NEP inhibitor phosphoramidon. Immunohistochemical analysis of normal chorionic villi and choriocarcinoma tissues revealed the localization of NEP in syncytiotrophoblastic cells, as opposed to weak or negative staining in cytotrophoblastic cells. These data demonstrate that induction of choriocarcinoma cell differentiation is associated with an increase of NEP/CD10 expression at the cell surface, suggesting a role of this enzyme in regulating differentiated trophoblast functions such as hCG secretion. NEP/CD10 may also be a new cellular differentiation marker of both the normal and neoplastic trophoblast.

Cell Differentiation↗
PubMed2001

Progressive interstitial renal fibrosis due to Chinese herbs in a patient with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome.

A 58-year-old woman with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome presented with slowly progressive renal dysfunction. She was normotensive with normal plasma renin activity and lacking symptoms of vasculitis. Mild proteinuria was of tubular origin, but serological tests and an absence of sicca symptoms excluded the possibility of Sjögren's syndrome. Light microscopic study of renal biopsy showed interstitial fibrosis with ectasia and degeneration of proximal tubule and lymphocyte infiltration. There were no remarkable changes in the glomeruli. Chromatographic analysis of the Chinese herbs regimen that she had been taking for several years demonstrated aristolochic acid. She was diagnosed as Chinese herbs nephropathy. Therapy with oral prednisolone was markedly effective in improving renal function and anemia. To our knowledge, this is the first report of Chinese herbs nephropathy complicating connective tissue disease. It is important to consider the possibility of Chinese herbs nephropathy when patients treated with Chinese herbs develop renal dysfunction.

Aristolochic Acids↗
PubMed2000

Hypercalcemia induced by metastatic bone cancer in a patient with chronic renal failure.

We present a diagnostically challenging case of hypercalcemia in a 50-year-old Japanese woman with chronic renal failure due to chronic interstitial nephritis. She had a history of a radical mastectomy for breast cancer at the age of 30. Despite her chronic renal failure, serum levels of calcium and alkaline phosphatase were abnormally high, and levels of intact parathyroid hormone and of parathyroid hormone-related protein were undetectable on repeated assays. Bone scintigram revealed multiple hot lesions in the ribs, which were suggestive of bone metastases of breast cancer. After treatment with tamoxifen citrate was initiated, her serum calcium levels returned to the normal range and hot lesions were no longer evident on bone scintigraphy in 14 months. Thus, our patient's hypercalcemia was considered to be related to bone metastases of breast cancer. Physicians should be aware of existence of malignancy in the patient with chronic renal failure and hypercalcemia.

Alkaline Phosphatase↗
PubMed1998

[Does left ventricular wall motion of akinetic segment improve after reperfusion therapy in patients with acute myocardial infarction?: assessment by myocardial contrast echocardiography].

The relationship between myocardial perfusion and left ventricular wall motion was studied by myocardial contrast echocardiography in 22 patients with acute myocardial infarction treated by successful direct percutaneous transluminal coronary angioplasty (PTCA). Myocardial contrast echocardiography was performed 4 times to assess the serial changes of wall motion score and opacification score, before and immediately after PTCA, and 2 weeks and 3 months after the onset of infarction, by injecting 2 ml Albunex into the infarct-related artery. Two-dimensional echocardiography was visualized at the level of the papillary muscle on the short-axis view or apical long-axis view. Wall motion score was graded visually as grade 0: dyskinesis/akinesis, to 3: normokinesis/hyperkinesis and opacification score was graded as grade 0: no opacification, to 2: homogeneous opacification using the 6-segment model of the short-axis view or 5-segment model of the apical long-axis view. Immediately after PTCA, we observed 30 segments with the dyskinesis/akinesis, which were divided into 3 groups (no opacification group, partial opacification group and homogeneous opacification group) by opacification score immediately after PTCA. The recovery of left ventricular wall motion in the partial opacification group (10 segments) and homogeneous opacification group (7 segments) were significantly better than the no opacification group (13 segments). Six (46%) of 13 segments in the no opacification group had improved contrast enhancement 3 months later, and 4 of these 6 segments showed improved left ventricular wall motion. The area opacified immediately after PTCA showed recovery of left ventricular wall motion in the chronic stage. However, some segments of the no-opacified area immediately after PTCA also showed improved myocardial opacification as well as improved left ventricular wall motion in the chronic stage. The results suggest that myocardial contrast echocardiography is an important method to predict myocardial viability, but it is difficult to assess the viability by contrast enhancement performed only in the acute stage of acute myocardial infarction.

Adult↗