Biomedical subjects

M Oikawa

Publications and source records attributed to M Oikawa.

At least 19 recordsLinked to original sources

PubMed2006

Demonstration of inter- and intracellular distribution of boron and gadolinium using micro-proton-induced X-ray emission (Micro-PIXE).

Micro-proton-induced X-ray emission (Micro-PIXE) was applied to determine inter- and intracellular distribution of boron (10B) and gadolinium (157Gd), the capture atoms used to kill tumor cells in neutron capture therapy (NCT). Cultured 9L gliosarcoma cells on Mylar film were exposed to sodium borocaptate (BSH) and gadobenate dimeglumine (Gd-BOPTA). To analyze the inter- and intracellular distribution of 10B and 157Gd in 9L gliosarcoma cells, the cells were irradiated using a proton beam of 1.7 or 3 MeV energy collimated to 1 microm diameter and emission X-ray was detected. The distribution of 10B and 157Gd in 9L gliosarcoma cells was then examined. In this study, we could directly analyze the inter- and intracellular distribution of 10B and 157Gd elements in 9L gliosarcoma cells directly using Micro-PIXE. This is the first report on the distribution of 10B employing a method to detect gamma-rays resulting from the nuclear reaction of 10B using particle-induced gamma-ray emission (PIGE). These results show that the distribution of 157Gd elements was correctly measured using micro-PIXE. 157Gd should have the same tendency as 10B in cultured 9L gliosarcoma cells and agree with the distribution in 9L gliosarcoma cells. Further investigation is necessary for a higher spatial resolution and optimization of the measurement time or improvement of the sampling method. In the future, it will be possible to employ this method to analyze the intracellular microdistribution of the capture element and in the development of new drugs for NCT.

Boron↗

PubMed2005

Mesenteric arterionecrosis in natural and experimental equine endotoxaemia.

To test the hypothesis that mesenteric arterionecrosis (MA) occurs in horses with naturally occurring endotoxaemia (ET) and in those with experimentally induced ET, the mesentery and gastrointestinal tract of 21 Thoroughbred racehorses (15 with spontaneous colic suspected to be due to ET, and six with experimentally induced ET) were examined. MA, which occurred in 13 of the 15 horses with spontaneous colic and in all six of the cases of experimental ET, was morphologically similar in the two groups of animals. This suggested that the pathogenesis of the MA was fundamentally similar in the two groups, and that MA is a pathognomonic feature of equine ET. In addition to histolysis of the arterial walls associated with infiltration of blood components, changes were noted in the medial smooth muscle including formation of many intracellular vacuoles within single smooth muscle cells, cytoplasmolysis, necrosis with granules and vacuoles, and coagulation necrosis; similar changes have been observed in cases of prolonged angiospasm or vasoconstriction. It is suggested that the effects of sustained arterial contraction leading to intimal and medial damage influence the pathomorphogenesis of MA.

Animals↗

PubMed2005

Fractures sustained by racehorses in Japan during flat racing with special reference to track condition and racing time.

The purpose of this report is to describe the results of epidemiological surveys of racing-related fractures in Thoroughbred horses in Japan. In the period 1987-2000, a total of 10,203 fractures were diagnosed in 556,705 runners, resulting in an overall incidence of 1.83%. The annual incidence of fractures in flat racing during the 14-year period fluctuated between 1.44% and 2.19%. The majority of fractures affected the forelimbs. We found significant effects of track condition on injury incidence. The incidence of fractures decreased as track conditions on turf became softer and increased as track conditions on dirt became muddier. Because of the general trend for the incidence of fractures to vary with track condition, we examined the relationship between track conditions and racing times for winning horses in 4117 races and for 50,564 overall runners for the period 1990-1994 on two tracks. For turf courses, racing times became longer as track conditions became softer. In contrast, for dirt courses, racing time tended to become shorter in muddier conditions. The variation in the incidence of fracture with track condition might be due to the corresponding difference in racing time.

Animals↗

PubMed2005

[Castleman disease of the inter-lobar lymph node origin].

We report a case of Castleman disease which originated from the inter-lobar lymph node, with a review of literatures. A 19-year-old woman complaining of cough was pointed out to have an abnormal shadow in the left lung field on chest X-ray. Chest computed tomography (CT) and magnetic resonance imaging (MRI) with enhancement revealed a homogeneous mass lesion at the left inter-lobar portion of the lung. Bronchoscopic findings demonstrated mucosal telangiectasis of the left lower bronchus. We performed the usual axillary thoracotomy and succeeded in extirpation of the tumor without large amount of bleeding. The tumor was elastic and hard, and 70 x 55 x 45 mm in size. Her postoperative course was uneventful and she was discharged on the 12th postoperative day.

Adult↗

PubMed2004

Arterionecrosis of the equine mesentery in naturally occurring endotoxaemia.

This report describes the mesenteric arteriolar lesions in a Thoroughbred racehorse with endotoxaemia due to colic. The vascular lesions consisted of a striking loss of medial smooth muscle cells, associated with granular cell debris derived from necrosed muscle cells, plasma insudation, erythrocyte infiltration and the deposition of a fibrinoid substance (fibrinoid degeneration) in the entire arterial wall, possibly produced by the infiltration of blood components through endothelial cell junctions into the arterial wall. The morphology of the mesenteric arteriolar necrosis closely resembled that seen in experimental equine endotoxaemia and in horses that died from colic; it also resembled that of Shiga toxin-induced arteriolar lesions in oedema disease of swine and of the arterionecrosis in human cerebral arteries that may lead to hypertensive intracerebral haemorrhage.

Animals↗

PubMed2003

Extranodal lymphoblastic lymphoma of suspected B-cell lineage in the gingiva of a racehorse, accompanied by mandibular osteolysis.

A mass developed in the mandibular gingiva of a thoroughbred racehorse. When the horse could no longer eat unassisted, it was killed and immediately autopsied. Macroscopically, the mandible exhibited extensive osteolysis, with only a small amount of bone remaining around the tooth roots. The cut surface of the mass around the mandible consisted of neoplastic medullary tissue, in which osteogenesis was observed. The medullary tissue was composed of pleomorphic medium-sized to large cells, interlaced by collagen bundles. These cells had large, pale, round or ovoid, sometimes cleaved nuclei, with one or two prominent nucleoli. Mitoses were numerous. Electron microscopy showed that the cells in the medullary tissues were similar in shape to undifferentiated lymphocytes. Immunohistochemically, these cells were positive for B-cell associated antigen in the pre-B-cell stage. Our findings suggest that the horse had extranodal lymphoblastic lymphoma of suspected B-cell lineage, possibly originating from the lymphatic system of the gingiva. We consider that the osteolysis resulted from activation of osteoclasts by proliferation of the tumour cells.

Animals↗

PubMed2002

Equine endotoxemia: pathomorphological aspects of endotoxin-induced damage in equine mesenteric arteries.

To evaluate the effects of endotoxin on the morphology of the equine mesenteric vasculature, each of two thoroughbred horses were given two intravenous injections (24 h apart) of a sublethal dose of endotoxin (10 microg/kg). Each injection produced results similar to those of clinical cases of equine colic with obstructive nature of the loop of bowel: diarrhoea within 2 h after administration, followed by cessation of both faecal excretion and sounds of intestinal peristalsis. The most prominent morphological change was the development of moniliform appearance of small mesenteric arteries, in which there were contracted and dilated segments of the small mesenteric arteries. This was accompanied by parietal hyalinization and intramural and extramural haemorrhage. These mesenteric vascular changes appear to reflect dynamic vasoconstriction in the living animal, resulting in reduction of mesenteric and intestinal blood flow and possibly inducing alterations of gastrointestinal function such as cessation of intestinal peristalsis.

Animals↗

PubMed2001

Hypoxia induces transcription factor ETS-1 via the activity of hypoxia-inducible factor-1.

ETS-1 plays an important role in angiogenesis and cancer invasion, and hypoxia is a common feature in these phenomena. We examined whether hypoxia influenced ETS-1 expression. Hypoxia induced ETS-1 in a human bladder cancer cell line, T24, and promoter analysis revealed that the deletion of -424 to -279 bp from the human ETS-1 promoter decreased the hypoxia-mediated inducibility. This region contained a hypoxia responsive element-like sequence, and HIF-1 bound to it under the hypoxic condition. Double-stranded synthetic oligonucleotides of this sequence as a decoy inhibited the hypoxia-mediated inducibility. These results indicate that hypoxia induces ETS-1 via the activity of HIF-1.

Base Sequence↗

PubMed2001

Surfactant proteins in bronchoalveolar lavage fluid of horses: assay technique and changes following road transport.

An enzyme-linked immunosorbent assay (ELISA) was developed for equine surfactant proteins SP-A and SP-D in bronchoalveolar lavage fluid (BALF). Anti-equine SP-A or SP-D monoclonal antibodies (mAb) were produced by hybridoma technology, purified by the antibody purification reagent, and analysed by Western blotting analysis. The immunoreaction (two-site sandwich ELISA) with a mAb, peroxidase-labelled mAb and BALF sample was carried out simultaneously and analytical recovery and precision were assayed. Six mAb for SP-A and four mAb for SP-D were successfully cloned in limiting dilution to monoclonality. These mAb were reacted with equine SP-A or SP-D on Western blotting analysis. For SP-A, a combination of solid-phase TA08 and horseradish peroxidase (HRP)-conjugated WA28 was found to be more sensitive than other combinations, gave a good dose response and was capable of measuring 0.78 to 100 ng of protein/ml. For SP-D, a combination of solid-phase TD13 and HRP-conjugated WD19 was found to be more sensitive than other combinations, had a good dose response and was capable of measuring 0.78 to 200 ng of protein/ml. The assay was used to determine the effect of 41 hours of road transport on the concentrations of SP-A and SP-D in the BALF of 30 horses. The concentrations of SP-A and SP-D decreased by 55 per cent and 36 per cent, respectively, decreases similar to the decrease in phosphatidylglycerol concentration previously reported by the authors.

Animals↗

PubMed2001

Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition.

Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS). MD-2 is associated with TLR4 and imparts LPS responsiveness to it. Little is known, however, as to whether MD-2 directly regulates LPS recognition by TLR4. To address the issue, we took advantage of a species-specific pharmacology of lipid IVa, an analogue of lipid A. Lipid IVa acted agonistically on mouse (m) TLR4/MD-2 but not on human (h) TLR4/MD-2. Lipid IVa antagonized the agonistic effect of lipid A on hTLR4/MD-2. We examined the chimeric complex consisting of mTLR4 and hMD-2 to ask whether species specificity is conferred by TLR4 or MD-2. hMD-2 was clearly distinct from mMD-2 in the way of influencing LPS recognition by mTLR4. hMD-2 conferred on mTLR4 responsiveness to lipid A but not to lipid IVa. Moreover, lipid IVa acted as a lipid A antagonist on mTLR4 that is associated with hMD-2. Collectively, MD-2 directly influences the fine specificity of TLR4.

Adjuvants, Immunologic↗

PubMed2001

Retinoic acids repress the expression of ETS-1 in endothelial cells.

The transcription factor ETS-1 expressed in endothelial cells (ECs) regulates angiogenesis by inducing MMP-1, MMP-3, MMP-9, u-PA and integrin beta3 in endothelial cells (ECs). Here, we examined whether antiangiogenic retinoic acids affect the expression of ETS-1 in ECs. The expression of ets-1 mRNA was up-regulated in sparse to subconfluent ECs and down-regulated in confluent ECs. When confluent ECs were stimulated with basic fibroblast growth factor (bFGF), ets-1 mRNA was induced. All-trans retinoic acid (ATRA) as well as 9-cis retinoic acid reduced the augmented expression of ets-1 mRNA in both subconfluent ECs and bFGF-treated confluent ECs. This inhibitory effect of ATRA was dose dependent and was evident at a concentration as low as 10(-7) M. ATRA did not alter the stability of ets-1 mRNA. Moreover, promoter analysis indicated that ATRA repressed the expression of ets-1 mRNA at transcriptional level. As a result, ATRA reduced the binding of ETS-1 protein to the ETS binding motif. These results indicate that the anti-angiogenic effect of retinoic acids is mediated at least in part by the transcriptional repression of ets-1 mRNA in ECs.

Alitretinoin↗

PubMed2001

[Possible inhibitory mechanism of liver regeneration through non-parenchymal cells after combined hepatectomy and pancreatectomy].

BACKGROUND: Recently, simultaneous hepatectomy (Hx) and pancreaticoduodenectomy have been performed in the treatment of biliary tract cancer. Postoperative hepatic failure is a common and potentially fatal complication. The aim of this study was to examine the reduced rate of liver regeneration after 70% Hx alone or in combination with 70% pancreatectomy (HPx). MATERIALS AND METHODS: Male Sprague-Dawley rats underwent Hx or combined Hx and Px. The ratio of liver-body weight, labeling index of hepatocytes in vivo, and DNA synthesis of hepatocytes and/or Kupffer cells in primary culture were analyzed. RESULTS: The ratio of liver-body weight in HPx rats was found to be significantly lower than that in Hx rats from 12 hours to 72 hours after surgery. There was no difference in blood glucose or ALT levels between the two groups. An inhibitory effect on DNA synthesis was observed in cocultured hepatocytes and Kupffer cells when portal plasma obtained one hour after surgery was added. We further observed that conditioned medium of Kupffer cells stimulated by portal plasma obtained one hour after HPx inhibited DNA synthesis by hepatocytes. This effect was abolished after incubation at 56 degrees C for 30 min. CONCLUSIONS: These results clearly indicate the existence of a growth inhibitory factor in portal serum after HPx. This heat-labile growth inhibitory factor was released from Kupffer cells stimulated by portal plasma after HPx and appears to act on hepatocytes in a paracrine manner.

Animals↗

PubMed2000

Out of plane measurements of the decay neutron from the giant resonance in the 12C(e,e(')n)11C reaction

Out of plane measurements of the angular correlations for the 12C(e, e(')n) reaction have been performed for the first time in the giant resonance region. The cross sections were directly separated into the longitudinal and transverse, longitudinal-transverse, and transverse-transverse components. The cross section at the peak of the giant resonance ( omega = 22.5 MeV) has been found to be almost all longitudinal. It was reproduced by the multipole expansion with E0 and E2 components besides E1. The longitudinal-transverse component might have a maximum around 24 MeV. The transverse-transverse component is very small over the giant resonance.

Journal Article↗

PubMed2000

Prognostic significance of lymph node metastasis and clear cell histology in ovarian carcinoma limited to the pelvis (pT1M0 and pT2M0).

BACKGROUND: The prognostic significance of lymph node (LN) metastasis in clinically early-stage (pT1M0 or pT2M0) ovarian carcinoma has not yet been fully elucidated. METHODS: From 1988 to 1997, 94 patients with ovarian carcinoma of pT1M0 (n = 78) or pT2M0 (n = 16) classification underwent surgery including systematic pelvic and paraaortic LN dissection. We investigated the prognostic factors of intraperitoneally determined early-stage ovarian carcinoma focusing on LN metastasis. RESULTS: LN metastasis was seen in 5.1% of pT1M0 and in 31.3% of pT2M0 tumors. Univariate analysis of grade, histology (clear cell vs others), size of primary tumor, peritoneal cytology, and LN metastasis revealed that histology (P < 0.01), size of tumor (P < 0.05), and LN metastasis (P < 0.0005) were related to patient survival of early-stage ovarian carcinoma. Peritoneal cytology (P = 0.053) and grade (P = 0.059) had marginal statistical significance. A multivariate Cox regression analysis showed that clear cell histology (P < 0.05) and LN metastasis (P < 0. 005) are significant independent prognosticators of patient survival. Three (two with clear cell adenocarcinoma and one with mucinous adenocarcinoma) of nine patients with LN metastasis had died of the disease by the time of the present analysis. Two of the three deceased patients had recurrent tumors in distant organs (bone and brain/liver), one had pleural and peritoneal carcinomatosis, and no patients had retroperitoneal recurrence. This suggests that LN metastasis indicates that tumor cells may have already spread systemically at the time of treatment and, at the same time, retroperitoneal lymph node dissection (RPLND) may be effective in eradicating retroperitoneal metastasis in some instances of ovarian carcinoma. CONCLUSION: Clear cell histology and LN metastasis are indicators of poor prognosis for patients with tumors limited to the pelvis. Therapeutic significance of systematic RPLND for pT1M0/pT2M0 ovarian carcinomas needs to be further investigated by randomized studies.

Adenocarcinoma, Clear Cell↗

PubMed2000

Signal transduction and transcriptional regulation of angiogenesis.

When quiescent endothelial cells (ECs) are exposed to angiogenic factor such as VEGF; ECs express proteases to degrade extracellular matrices, migrate, proliferate and form new vessels. However, the molecular mechanism of these events is not fully characterized yet. We are studying the signal transduction and transcriptional regulation of angiogenesis. We investigated the properties of two VEGF receptors, Flt-1 and KDR, by using two newly developed blocking monoclonal antibodies (mAbs), i.e., anti-human Flt-1 mAb and anti-human KDR mAb. VEGF elicited induction of transcription factor Ets-1 in human umbilical vein endothelial cells (HUVECs). This induction was mediated by the KDR/Flt-1 heterodimer and the KDR homodimer. The role of transcription factor Ets-1 in angiogenesis was further clarified. We established both high and low Ets-1 expressing EC lines, and compared angiogenic properties of these cell lines with a parental murine EC line, MSS31. The growth rate was almost identical among three cell lines. It appeared that gene expressions of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9) as well as integrin beta 3 were correlated with the level of Ets-1 expression. As a result, the invasiveness was enhanced in high Ets-1 expressing cells and reduced in low Ets-1 expressing cells compared with parental cells, and high Ets-1 expressing cells made more tube-like structures in type 1 collagen gel. These results indicate that Ets-1 is a principle transcription factor converting ECs to the angiogeneic phenotype.

Animals↗

PubMed2000

Changes in levels of biochemical markers and ultrasound indices of Os calcis across the menopausal transition.

The aim of this longitudinal study was to investigate the changes in the levels of biochemical markers and ultrasound indices of os calcis across the menopausal transition. One hundred and ten healthy women (age 35-59 years at the 1992 baseline) participated in this 4-year population-based longitudinal study. Serum intact osteocalcin (IOC), urinary pyridinoline (Pyr), urinary deoxypyridinoline (Dpyr) and ultrasound indices were measured at baseline and after 4 years. The percentage changes in biochemical markers (% delta IOC, % delta Pyr and % delta Dpyr) and the percentage decreases in the ultrasound indices (% delta SOS, % delta BUA and % delta Stiffness) were calculated. The values of % delta IOC and % delta Dpyr in the perimenopausal subgroup (-4 to -3 years since menopause) and the values of % delta SOS and % delta Stiffness in the perimenopausal subgroup (-2 to 0 years since menopause) were significantly higher than those in other groups. Pyr was significantly correlated with % delta SOS (r = -0.467, p < 0.01) and % delta Stiffness (r = -0.330, p < 0.05) and Dpyr was significantly correlated with % delta SOS (r = -0.390, p < 0.05), % delta BUA (r = -0.353, p < 0.05) and % delta Stiffness (r = -0.454, p < 0.05), while % delta IOC was significantly correlated with % delta SOS (r = -0.278, p < 0.05), % delta BUA (r = -0.369, p < 0.01) and % delta Stiffness (r = -0.383, p < 0.01) in the peri- and postmenopausal groups. These results indicate that the increase in bone turnover occurs 4 years before menopause. However, the correlations between biochemical markers and ultrasound indices were too low to allow prediction of bone change in the individual patient.

Adult↗

PubMed2000

Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity.

Lipopolysaccharides (LPS, endotoxin) represent a major virulence factor of Gram-negative bacteria, which can cause septic shock in mammals, including man. The lipid anchor of LPS to the bacterial outer membrane, lipid A, exhibits a peculiar chemical structure, harbours the 'endotoxic principle' of LPS and is also responsible for the expression of pathophysiological effects. Chemically modified lipid A can be endotoxically inactive, but may express strong antagonistic activity against endotoxically active LPS. By applying orientation measurements with attenuated total reflectance (ATR) infrared spectroscopy on hydrated lipid A samples, we show here that these different biological activities are directly correlated to the intrinsic conformation of lipid A. Bisphosphoryl-hexaacyl lipid A molecules with an asymmetric (4/2) distribution of the acyl chains linked to the diglucosamine backbone have a large tilt angle (> 45 degrees ) of the diglucosamine backbone with respect to the membrane surface, a conical molecular shape (larger cross-section of the hydrophobic than the hydrophilic moiety), and are endotoxically highly active. Monophosphoryl hexaacyl lipid A has a smaller tilt angle, and the conical shape is less expressed in favour of a more cylindrical shape. This correlates with decreasing endotoxic activity. Penta- and tetraacyl lipid A or hexaacyl lipid A with a symmetric acyl chain distribution (3/3) have a small tilt angle (< 25 degrees ) and a cylindrical shape and are endotoxically inactive, but may be antagonistic.

Carbohydrate Conformation↗

PubMed2000

Esophageal squamous cell carcinoma characterized by extensive chondroid differentiation.

A rare case of carcinoma characterized by extensive chondroid elements at a site of primary esophageal and metastatic lesion is reported. The patient was a 67-year-old man complaining of dysphagia due to an ulcerative lesion at the lower middle esophagus. He underwent irradiation treatment prior to surgery. Histologically, the tumor consisted of both carcinomatous and chondroid elements and had invaded deeply into the esophageal wall. The carcinomatous cells had gradually become chondroid cells embedded within an extensive extracellular matrix. In addition, the metastatic lesion showed findings similar to those of the primary lesion. Immunohistochemistry revealed that both carcinomatous and chondroid elements were immunostained with cytokeratin and epithelial membrane antigen, suggesting an epithelial nature to the chondroid cells. Conversely, only chondroid cells were positively stained for S-100 protein. Furthermore, bone morphogenetic proteins (BMP) were positive for chondroid cells and their surrounding carcinomatous cells. Given the apparent transition between carcinomatous and chondroid cells based on microscopy and immunohistochemical findings in the present case, we concluded that the chondroid cells were derived from carcinomatous cells. In addition, our findings suggest that BMP produced by carcinomatous cells lead to chondroid differentiation of the carcinoma cells.

Aged↗