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Biomedical subjects

K Sonoda

Publications and source records attributed to K Sonoda.

At least 19 recordsLinked to original sources

Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer.

Epidermal growth factor receptor (EGFR) has been implicated in tumour growth and extension of ovarian cancer. Peritoneal fluid in ovarian cancer patients contains various growth factors that can promote tumour growth and extension. In order to investigate the clinical significance of EGFR ligands as activating factors of ovarian cancer, we examined the cell proliferation-promoting activity and the level of EGFR ligands in peritoneal fluid obtained from 99 patients. Proliferation-promoting activity in peritoneal fluid from 63 ovarian cancer patients (OVCA) was much higher than peritoneal fluid from 18 ovarian cyst patients (OVC) and 18 normal ovary patients (NO), and the activity was suppressed only by antibodies against EGFR or heparin-binding epidermal growth factor (HB-EGF). A large difference was observed in the level of EGFR ligands between HB-EGF and TGF-alpha or amphiregulin. The concentration of HB-EGF in OVCA significantly increased compared to that in OVC or NO (P<0.01). No significant difference in the concentration of TGF-alpha and amphiregulin was found between the OVCA and NO or OVC groups. In peritoneal fluid, HB-EGF is sufficiently elevated to activate cancer cells even at an early stage of OVCA. These results suggested that HB-EGF in peritoneal fluid might play a key role in cell survival and in the proliferation of OVCA.

Amphiregulin↗

Laparoscopically assisted distal gastrectomy for early gastric cancer in the elderly.

BACKGROUND: Open gastrectomy is associated with increased morbidity and a longer hospital stay than laparoscopically assisted gastrectomy. The aim of this study was to clarify the value of laparoscopically assisted distal gastrectomy (LDG) in the elderly, in whom co-morbid disease is generally more common. METHODS: Forty-five elderly patients (aged 70 years or more) and 57 younger patients who underwent LDG, and 28 elderly patients who underwent open distal gastrectomy (ODG) for early gastric cancer between January 1994 and April 2003 were studied. Demographics and postoperative outcomes were compared. RESULTS: : Co-morbidity was more common in elderly patients than in younger patients who underwent LDG (25 of 45 versus 16 of 57; P = 0.004). The postoperative complication rate, time to solid diet and postoperative hospital stay were similar in these two groups. Elderly patients who underwent LDG had a significantly reduced medical complication rate (two of 45 versus six of 28; P = 0.023), time to first flatus (3.7 versus 4.2 days; P = 0.042), time to solid diet (4.6 versus 5.5 days; P = 0.011) and postoperative hospital stay (16.3 versus 23.9 days; P = 0.011) than elderly patients who had ODG. CONCLUSION: LDG offers particular advantages to elderly patients with early gastric cancer, including rapid return of gastrointestinal function, fewer complications and a shorter hospital stay.

Aged↗

Association between RCAS1 expression and clinical outcome in uterine endometrial cancer.

RCAS1, which acts as a ligand for a putative receptor on immune cells such as peripheral lymphocytes and natural killer cells, is strongly expressed in human cancers. RCAS1 can induce these cells to undergo apoptotic cell death, which suggests that RCAS1 expression may prohibit the stromal reaction occurring in a tumour. To clarify the clinical significance of RCAS1 expression in uterine endometrial cancer, we analysed the association between RCAS1 expression and clinicopathologic variables by statistical methods. With the use of immunohistochemical techniques, we performed a retrospective study of RCAS1 expression in resected tumour tissue from 147 patients with uterine endometrial cancer. We evaluated the statistical correlation between RCAS1 expression and clinicopathologic variables. RCAS1 was expressed in 106 of 147 patients with uterine endometrial cancer; 30 of these 147 patients showed RCAS1 overexpression. Overexpression of RCAS1 was significantly correlated with age at surgery, stage, extent of myometrial invasion, and positive peritoneal cytologic results. Multivariate analysis revealed that RCAS1 expression and metastasis were clinically significant prognostic factors for the overall survival. These findings indicated that analysis for RCAS1 expression can provide crucial information about the clinical behaviour of uterine endometrial cancer, which may be valuable for the management of patients with this disease.

Adult↗

T lymphocyte subsets and Th1/Th2 balance after laparoscopy-assisted distal gastrectomy.

BACKGROUND: Laparoscopic surgery provides for a less invasive procedure than open surgery in patients with gastric cancer, but the immune responses after laparoscopic surgery for early gastric cancer remain unknown. METHODS: Peripheral blood mononuclear cells from 20 patients with early gastric cancer who underwent laparoscopy-assisted distal gastrectomy (LADG) or open distal gastrectomy (ODG) were obtained; the cell surface molecules and intracellular cytokines (IFN-gamma and IL-4) were measured by flow cytometry. RESULTS: The populations of T lymphocytes after LADG, including CD3-, 4-, 8-, 57-, and HLA-DR-positive lymphocytes, showed patterns similar to those after ODG. The production of IFN-gamma as Th1 cell function decreased significantly on the third postoperative day after ODG but increased after LADG. The production of IL-4, representing Th2 cell function, increased postoperatively after ODG but not after LADG. CONCLUSIONS: When compared with ODG, LADG contributes to the preservation of postsurgical Th1 cell-mediated immune function.

Aged↗

A hydroxyapatite coating covalently linked onto a silicone implant material.

A novel composite consisting of hydroxyapatite (HAp) microparticles covalently coupled onto a silicone sheet was developed. Initially, an acrylic acid (AAc) -grafted silicone sheet with a 16.7 microg/cm(2) surface graft density was prepared by corona-discharge treatment. The surface of sintered, spherical, carbonated HAp particles with an average diameter of 2.0 microm was subsequently modified with amino groups. The amino group surface density of the HAp particles was calculated to be approximately one amino molecule per 1.0 nm(2) of particle surface area. These samples were characterized with Fourier transform infrared spectrometry and X-ray photoelectron spectroscopy. After the formation of ammonium ionic bonds between both samples under aqueous conditions, they were reacted at 180 degrees C for 6 h in vacuo to form covalent bonds through a solid-phase condensation. The HAp particles were coupled to the AAc-grafted silicone surface by a covalent linkage. Further improvements in the adhesive and bioactive properties of the HAp-coated silicone material are expected.

Acrylates↗

Expression of RCAS1 and FasL in human trophoblasts and uterine glands during pregnancy: the possible role in immune privilege.

Pregnancy is an immunological balancing act. Trophoblasts do not express MHC class I or II, except HLA-C and G, but express Fas ligand (FasL), which confers immune privilege. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) has recently been recognized to play a role in immune evasion of the tumour cells. We therefore studied the involvement of RCAS1 and FasL in the infiltration of NK cells by examining the curettaged uterine contents of 20 cases of early stage of pregnancy. The cases were clinically divided into two groups; curettage was performed (A) due to the absence of foetal heart beats, and (B) due to spontaneous uterine bleeding and abortion. In group A, RCAS1 was expressed in the uterine glands and extravillous cytotrophoblasts, as was FasL. Infiltration of NK cells around the uterine glands was scarcely detected. In contrast, in group B, expression of both RCAS1 and FasL was strikingly decreased in both the level of expression and the numbers of RCAS1/FasL-positive cells and massive infiltration of NK cells was frequently detected around the uterine glands. These findings suggest that a reduction in RCAS1 and FasL expression seems to be closely associated with activation and infiltration of maternal NK cells and destruction of uterine glands, resulting in rejection of the foetus. Thus, expression of RCAS1 and FasL in the uterine glands and cytotrophoblasts may play a role in the downregulation of the maternal immune response, thereby maintaining pregnancy at early stage.

Abortion, Spontaneous↗

Ivermectin treatment of demodicosis in 56 hamsters.

Fifty-six hamsters with demodicosis were treated with daily oral administration of ivermectin (0.3 mg/kg). Thirty-three cases (58.9%) were cured and 6 cases (10.7%) had improved clinically but needed to continue treatment. Of 5 cases (8.9%) who relapsed within 3 months and were retreated with ivermectin, 4 were cured and 1 needed further treatment. Five cases (8.9%) had improved clinically but died within 3 months. Seven cases (12.5%) had not improved and died within 3 months. Overall 49 (87.5%) hamsters had improved clinically. No significant differences in prognosis of demodicosis were detected according to sex, breed, age and clinical features, but the prognosis of demodicosis in hamsters with concurrent disease was poor.

Animals↗

[Treatment outcomes with vinorelbine for metastatic breast cancer patients previously treated with both doxorubicin and docetaxel].

The purpose of this study was to evaluate the efficacy and toxicity of weekly vinorelbine (VNB) in patients with metastatic breast cancer previously treated with both adriamycin (ADM) and docetaxel (TXT). VNB was administered weekly at the dose 20 mg/m2 by i.v. infusion over 20 minutes followed by flushing the vein with 100 ml of normal saline. From June 1999 to August 2000, ten patients were enrolled in this study. Patient characteristics were that the cumulative doses (median) of previous ADM and TXT were 300 mg (range, 120-880 mg), 560 mg (range, 120-960 mg) respectively. The median number of metastatic sites was four, with poor performance status (ECOG 1-2: 40%, 3-4: 60%). The median cycles of weekly VNB were seven (range: 2-12). Two of 10 assessable patients obtained partial response, with an overall response rate of 20%. The main toxicity (NCI grade 4) was leukopenia in 10% of 10 patients. Phlebitis (grade 2) was observed in 4 of 10 patients (40%). VNB is an active agent against metastatic breast cancer pretreated with both ADM and TXT, possessing no severe toxicities.

Adult↗

Acute rejection of orthotopic corneal xenografts in mice depends on CD4(+) T cells and self-antigen-presenting cells.

PURPOSE: Guinea pig corneal xenografts have been reported to be rejected acutely in eyes of normal adult mice. Rejection of this type is independent of xenoreactive antibodies, and mice deficient in CD8(+) and NK T cells are unable to reject guinea pig corneal grafts acutely. Therefore, a study was conducted to determine the extent and manner by which CD4(+) T cells are responsible for rejection of orthotopic corneal xenografts. METHODS: Xenogeneic corneas were prepared from eyes of normal guinea pigs and grafted orthotopically into normal eyes of C57BL/6 mice, class II major histocompatibility complex (MHC) knockout (KO) mice, and class II MHC KO mice reconstituted with syngeneic (C57BL/6) CD4(+) T cells and/or bone marrow cells. Graft survival was assessed clinically, and success of cellular reconstitution was assayed using flow cytometric analysis of peripheral blood leukocytes. T cells from rejector mice were analyzed for proliferative responses to guinea pig xenoantigens in vitro. RESULTS: Median survival times (MST) of corneal xenografts in MHC class II KO mice was significantly delayed (31 days) compared with grafts in wild-type C57BL/6 eyes (9 days). Acute rejection was restored almost completely when MHC class II KO mice were reconstituted simultaneously with C57BL/6 bone marrow and CD4(+) T cells, but not when the KO mice were reconstituted with either CD4(+) T cells or bone marrow cells alone. Mice that rejected guinea pig corneas possessed only CD4(+) T cells capable of responding to guinea pig xenoantigens in vitro. CONCLUSIONS: Acute rejection of orthotopic corneal xenografts in mice is mediated by CD4(+) T cells that detect guinea pig xenoantigens that are presented on MHC class II(+) syngeneic antigen-presenting cells. These results strongly suggest that rejection occurs exclusively through the indirect pathway of T-cell activation.

Acute Disease↗

The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic, and malignant uterine endometrium.

OBJECTIVE: A tumor-associated antigen, RCAS1, is recognized by 22-1-1 monoclonal antibody. It was found in carcinomas derived from the uterus and ovary and was especially strongly expressed in invasive cancers. A previous investigation showed the RCAS1 expression to be correlated with a poor prognosis in uterine cervical adenocarcinoma. In this study, we examined whether the expression of RCAS1 is associated with the progression of the uterine endometrial neoplasms. METHODS: The expression of RCAS1 was evaluated by an immunohistochemical analysis. The tissue specimens used in this study included 46 cases of normal uterine endometrium, 40 cases of hyperplasia, and 121 cases of adenocarcinoma. The relationship between RCAS1 expression and several clinicopathological variables (clinical stage, histology, grade, myometrial invasion, lymph-vascular space invasion, and lymph node metastasis) was also assessed in endometrial adenocarcinoma. RESULTS: RCAS1 was positive in 26% of the normal uterine endometrium specimens (12 of 46 total cases), in 32% of the hyperplasia specimens (13 of 40 total cases), and in 68% of the adenocarcinoma specimens (83 of 121 total cases). As a result, the expression of RCAS1 was statistically higher in adenocarcinoma than in the normal and hyperplastic endometrium (P < 0.0001). RCAS1 was statistically detected more frequently in grade 3 than in grade 1 or 2 (P < 0.05); however, there was no correlation between the antigen expression and the clinical stage, myometrial invasion, lymph-vascular space invasion, or lymph node metastasis. CONCLUSION: RCAS1 expression might thus be associated with the malignant transformation and poor differentiation observed in uterine endometrial adenocarcinoma.

Adenocarcinoma↗

Blockade of TGF-beta by in vivo gene transfer of a soluble TGF-beta type II receptor in the muscle inhibits corneal opacification, edema and angiogenesis.

Accumulating evidence suggests the involvement of TGF-beta in the process of corneal opacity, which is one of the serious causes of visual loss. However, whether TGF-beta is indeed critical for the pathogenesis remains unknown. We constructed an adenovirus expressing an entire ectodomain of the human type II TGF-beta receptor fused to Fc portion of human IgG (AdTbeta-ExR): this soluble receptor is secreted from AdTbeta-ExR-infected cells, binds to TGF-beta and inhibits TGF-beta signaling. When AdTbeta-ExR was injected into the femoral muscle of Balb/c mice, a high level of the soluble receptor protein (2.0-3.5 x 10(3) pM) was detectable in the serum and in the ocular fluid for at least 10 days. In the mice subjected to corneal injury with silver nitrate and to intramuscular injection with either saline or a control adenovirus expressing beta-galactosidase (AdLacZ), corneal opacification composed of extracellular matrix (ECM) accumulation, of infiltration of neutrophils and monocytes/macrophages, and of angiogenesis were all induced. In contrast, they were markedly reduced in the mice injected with AdTbeta-ExR. Immunohistochemical analysis revealed that TGF-beta, fibronectin, macrophage chemoattractant protein-1, and vascular endothelial growth factor were densely stained in the edge of wounded cornea, but they were scarcely present in the injured-cornea of AdTbeta-ExR-treated mice. Our results demonstrate that TGF-beta indeed plays a critical role in the process of cornea opacification, and that adenovirus-mediated expression of a soluble TGF-beta receptor can be therapeutically useful.

Adenoviridae↗

Development of an effective polyvalent vaccine against both Marek's and Newcastle diseases based on recombinant Marek's disease virus type 1 in commercial chickens with maternal antibodies.

An earlier report (M. Sakaguchi et al., Vaccine 16:472-479, 1998) showed that recombinant Marek's disease virus type 1 (rMDV1) expressing the fusion (F) protein of Newcastle disease virus (NDV-F) under the control of the simian virus 40 late promoter [rMDV1-US10L(F)] protected specific pathogen-free chickens from NDV challenge, but not commercial chickens with maternal antibodies against NDV and MDV1. In the present study, we constructed an improved polyvalent vaccine based on MDV1 against MDV and NDV in commercial chickens with maternal antibodies. The study can be summarized as follows. (i) We constructed rMDV1 expressing NDV-F under the control of the MDV1 glycoprotein B (gB) promoter [rMDV1-US10P(F)]. (ii) Much less NDV-F protein was expressed in cells infected with rMDV1-US10P(F) than in those infected with rMDV1-US10L(F). (iii) The antibody response against NDV-F and MDV1 antigens of commercial chickens vaccinated with rMDV1-US10P(F) was much stronger and faster than with rMDV1-US10L(F), and a high level of antibody against NDV-F persisted for over 80 weeks postvaccination. (iv) rMDV1-US10P(F) was readily reisolated from the vaccinated chickens, and the recovered viruses were found to express NDV-F. (v) Vaccination of commercial chickens having maternal antibodies to rMDV1-US10P(F) completely protected them from NDV challenge. (vi) rMDV1-US10P(F) offered the same degree of protection against very virulent MDV1 as the parental MDV1 and commercial vaccines. These results indicate that rMDV1-US10P(F) is an effective and stable polyvalent vaccine against both Marek's and Newcastle diseases even in the presence of maternal antibodies.

Animals↗

Phytophilous chironomidae (Diptera) and other macroinvertebrates in the ox-bow Infernão Lake (Jatai Ecological Station, Luiz Antonio, SP, Brazil).

Infernão Lake, located within the Jataí Ecological Station in Luiz Ant nio Municipal district (São Paulo State, Brazil), is one of the most typical ox-bow lake of the Mogi-Guaçu River, and it presents, as the main feature, its great quantity of aquatic macrophytes, whose intensive development, in the last years practically covered the whole mirror of water. With the purpose to point out the composition and to establish the relative participation of the phytophilic zoocoenosis that inhabits the different macrophytes of that lake, a collection program of the main vegetation stands was established. The collections, were carried out randomly, during dry season (1994), in stands of Salvinia auriculata, Utricularia sp., Cabomba piauhyensis, Eichhornia azurea and Scirpus cubensis being used specific methodology for each vegetable type. The analysis of the different macrophytes showed the presence of 4,130 macroinvertebrates of 28 families, in which Chironomidae (Diptera) and Naididae (Oligochaeta) were the most representative, contributing on the average with 51% and 25% of the total fauna. Asheum, Beardius, Chironomus, Goeldichironomus, Parachironomus and Polypedilum were the most abundant Chironomidae genera. Species of the genus Dero (Dero) and D. (Aulophorus) represented the most typical Naididac of the phytofauna. With clear faunistic gradient from the shore to the center of the lake, the taxocoenosis indicated low similarity (PSc < 50%), evidencing its own characteristics of each biotope. On the contrary, there was a high similarity (PSc > 60%) among the associated communities on different vegetables, when grouped into feeding guilds, with expressive participation, in most of the macrophytes, of the collector-gatherers category, except on S. auriculata, whose predators (> 50%) and collector-filterers (> 20%) dominance turned that zoocoenosis distinct from the others.

Animals↗

[Efficacy of UFT in the treatment of para-aortic lymph node metastasis following gastric cancer surgery: case report].

The patient was a 68-year-old man who underwent pyloric gastrectomy for advanced stomach cancer on December 6, 1996. The histopathological diagnosis was poorly differentiated adenocarcinoma, ss, ly3, v1, n2 (+), and stage IIIa. Postoperative adjuvant chemotherapy consisted of short-term intravenous infusion of 5-FU, 320 mg/m2/day (= 480 mg/body) for 5 days beginning on postoperative day (POD) 1, and oral 5-FU, 200 mg/day, for 1 year beginning on POD 14. The preoperative CEA value was 316.2 ng, but it fluctuated below 10 ng postoperatively. About one year after the operation, the patient began to complain of epigastric pain, loss of appetite, and general malaise. CT of the upper abdomen revealed a 1.5-cm para-aortic lymph node, and the CEA value of 319.0 ng was abnormally high. 5-FU was stopped, oral UFT at 300 mg/day was started, and the patient's course was followed. Three months after the start of UFT, the lymph node had shrunk on CT (shrinkage rate: 66.7%), and the CEA value had decreased to 14.3 ng. As though corresponding to these changes there was a gradual decrease in the epigastric pain, general malaise, etc., and the patient's appetite also returned. There were no subsequent elevations in the CEA values or increases in the size of the para-aortic lymph nodes, and the patient's general condition was favorably maintained. UFT appeared to be effective against the lymph node metastasis around the aorta in this case.

Adenocarcinoma↗

Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1.

Tumor-associated antigens that can be recognized by the immune system include the MAGE-family, p53, MUC-1, HER2/neu and p21ras. Despite their expression of these distinct antigens, tumor elimination by the immune system is often inefficient. Postulated mechanisms include insufficient expression of co-stimulatory or adhesion molecules by tumor cells, or defective processing and presentation of antigens on their cell surfaces. Tumor cells may also evade immune attack by expressing CD95 (APO-1/Fas) ligand or other molecules that induce apoptosis in activated T cells. Here we describe RCAS1 (receptor-binding cancer antigen expressed on SiSo cells), a membrane molecule expressed on human cancer cells. RCAS1 acts as a ligand for a putative receptor present on various human cell lines and normal peripheral lymphocytes such as T, B and NK cells. The receptor expression was enhanced by activation of the lymphocytes. RCAS1 inhibited the in vitro growth of receptor-expressing cells and induced apoptotic cell death. Given these results, tumor cells may evade immune surveillance by expression of RCAS1, which would suppress clonal expansion and induce apoptosis in RCAS1 receptor-positive immune cells.

Amino Acid Sequence↗

Spondylolysis at three sites in the same lumbar vertebra.

We report a rare case of spondylolysis that occurred at 3 sites in the fifth lumbar vertebra involving the bilateral pars interarticularis and the center of the right lamina. This is the first such case in the world literature.

Adolescent↗

Construction of the single-chain Fv from 196-14 antibody toward ovarian cancer-associated antigen CA125.

The variable regions of heavy- and light-chains of mouse monoclonal antibody 196-14 toward ovarian cancer-associated antigen CA125 were linked with a peptide linker (GSTSGSGKSSEGKG) and a histidine tag was attached at the carboxyl terminal. This single-chain Fv (scFv) with a histidine tag was expressed in Escherichia coli as an inclusion body. The inclusion body was solubilized with guanidium chloride, followed by purification on nickel nitrilotriacetic acid agarose column and refolding into the active form. The scFv thus obtained bound to the Siso cells, which express CA125, and may recognize the same epitope as the parental 196-14 antibody IgG does.

Animals↗