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Biomedical subjects

H Yamada

Publications and source records attributed to H Yamada.

At least 307 records · Page 17Linked to original sources
PubMed2000

The facilitation of peritoneal dissemination of a tumor by laparotomy in a rabbit model.

The effects of conventional laparotomy and laparoscopic surgery on the peritoneal dissemination of VX2 tumors were evaluated in a rabbit model. Either 5 x 10(3) or 5 x 10(4) of VX2 tumor cells were inoculated into the peritoneal cavities of rabbits which were divided into three groups according to the procedure performed, namely, a conventional laparotomy group (group 1), a laparoscopy group (group 2), and a control group (group 3). All the animals were killed 2 weeks after the treatment to examine the spread of the VX2 tumor in the omentum. In the experiment in which 5 x 10(3) tumor cells were inoculated, no significant difference was found in the number of metastases among the three groups. Conversely, after inoculating 5 x 10(4) tumor cells, the mean numbers of metastatic colonies greater than 1 mm in diameter in the greater omentum were 14.4+/-4.7 in group 1, 9.9+/-2.4 in group 2, and 3.3+/-1.1 in group 3, with a significant difference between groups 1 and 3, and between groups 2 and 3, but not between groups 1 and 2. In conclusion, conventional laparotomy facilitated the greatest peritoneal dissemination of a VX2 tumor in this animal model when 5 x 10(4) tumor cells were inoculated. Furthermore, laparoscopic surgery influences tumor growth to almost the same degree as conventional laparotomy.

Animals↗
PubMed2000

Gene cloning and overproduction of low-specificity D-threonine aldolase from Alcaligenes xylosoxidans and its application for production of a key intermediate for parkinsonism drug.

The dtaAX gene encoding a pyridoxal 5'-phosphate (pyridoxal-P)-dependent low-specificity D-threonine aldolase was cloned from the chromosomal DNA of Alcaligenes xylosoxidans IFO 12669. It contains an open reading frame consisting of 1,134 nucleotides corresponding to 377 amino acid residues. The predicted amino acid sequence displayed 54% identity with that of D-threonine aldolase from gram-positive bacteria Arthrobacter sp. DK-38, but showed no significant similarity with those of other known pyridoxal-P enzymes. This gram-negative bacterial enzyme was highly overproduced in recombinant Escherichia coli cells, and the specific activity of the enzyme in the cell extract was as high as 18 U/mg (purified enzyme 38.6 U/mg), which was 6,000 times higher than that from the wild-type Alcaligenes cell extract. The recombinant enzyme was thus feasibly purified to homogeneity by ammonium sulfate fractionation and DEAE-Toyopearl chromatography steps. The recombinant low-specificity D-threonine aldolase was shown to be an efficient biocatalyst for resolution of L-beta-3,4-methylenedioxyphenylserine, an intermediate for production of a therapeutic drug for Parkinson's disease.

Alcaligenes↗
PubMed2000

Effect of CO(2) pneumoperitoneum on growth of liver micrometastases in a rabbit model.

Little is known about the risk of metachronous liver metastases following laparoscopic resection for gastrointestinal malignancies. The effect of CO(2) pneumoperitoneum on the growth of established liver micrometastases was investigated in a rabbit model. Male Japanese white rabbits weighing 2.8 to 3.3 kg were randomized to three groups (n = 15 per group) 3 days following intraportal inoculation of a tumor suspension containing 5 x 10(4) cells of VX(2) cancer. In the pneumoperitoneum group, insufflation with CO(2) was maintained at a pressure of 10 mmHg for 30 minutes. In the laparotomy group the abdominal cavity remained open through a 45 mm midline incision for 30 minutes; in the control group no treatment other than anesthesia was performed. Cancer nodules on the liver surface were compared among the three groups on day 17. There was no difference in the number of cancer nodules among the groups (p = 0. 72). A significant difference in the total area of cancer nodules (mean +/- SEM) was found only between the pneumoperitoneum group (696.0 +/- 177.0 mm(2)) and the control group (247.2 +/- 60.7 mm(2)) (p < 0.05). The frequency of cancer nodules larger than 3.0 mm in maximal diameter tended to be highest in the pneumoperitoneum group (p = 0.053). These results suggests that CO(2) pneumoperitoneum may promote the growth of established liver micrometastases in this animal model.

Animals↗
PubMed2000

Relation between effective utilization of exogenous fat emulsion as energy substrate and oxygen metabolism after surgery.

It is known that fat oxidation is increased in patients who have sustained surgical stress, but it is not clear whether fat emulsion should be administered during the early postoperative period. The aim of this study was to evaluate the utilization of exogenous fat emulsion after major surgery. Total parenteral nutrition composed of glucose/amino acids or glucose/amino acids/fat was administered for 6 days to 18 patients who had undergone esophagectomy. The caloric intake was significantly less than the resting energy expenditure (REE), and there was no difference in substrate utilization in either group up to postoperative day (POD) 2. After POD 4, fat utilization was significantly increased in the fat group. The total ketone body concentration was higher in the fat group than in the glucose group on POD 1 and 2. The arterial ketone body ratio (AKBR), which reflects the rate of turnover of the Krebs cycle, was positively correlated with the caloric intake/REE ratio. It was negatively correlated with the oxygen delivery index, oxygen consumption, and lactate concentration between POD 0 and POD 2. The lactate concentration was decreased and the AKBR was increased by POD 4. Fat emulsion was effectively utilized as energy substrate after POD 4, after the relative tissue hypoxia had improved and the AKBR had increased. The utilization of exogenous fat emulsion was closely related to deficient caloric intake and oxygen metabolism.

Aged↗
PubMed2000

Expression of keratan sulfate at the arthroplasty surface after cup arthroplasty.

Fibrous tissue which regenerated on the acetabular arthroplasty surface was obtained from a 52-year-old woman who underwent total hip replacement after cup arthroplasty. The histological features of this newly formed fibrous tissue and expression of keratan sulfate, which is a characteristic matrix component of articular cartilage, were studied. Microscopic observation revealed that the arthroplasty surface consisted mainly of fibrous tissue which did not show metachromasia with toluidine blue staining, but there were many nodular structures communicating with the bone marrow. Immunostaining for keratan sulfate revealed clear positive staining around the cells of the nodular structures communicating with the bone marrow, while only weakly positive staining was observed in the superficial layer of the loose fibrous tissue. The present study revealed marked formation of articular cartilaginous tissue in areas having good communication with the bone marrow, which indicates that maintenance of this communication may be necessary to improve the outcome of cup arthroplasty.

Arthroplasty, Replacement, Hip↗
PubMed2000

Hyaluronan in synovial fluid of patients with loose total hip prosthesis. Comparison with hyaluronan in patients with hip osteoarthritis and idiopathic osteonecrosis of femoral head.

The concentration and molecular weight of hyaluronan (HA) in the synovial fluid of the hip joint were determined in 13 patients (aged 62.8 +/- 9.4 years) who had undergone prior total hip arthroplasty(THA), 23 patients (aged 65.0 +/- 8.2 years) with osteoarthritis of the hip joint (OA), and 13 patients (aged 40.2 +/- 2.7 years) with idiopathic osteonecrosis of the femoral head (ION). A sample of synovial fluid was obtained during revision THA because of loosening of the total hip prosthesis for the THA group, and during the first replacement surgery or osteotomy for the OA and ION groups. The concentration of HA in the synovial fluid was 0.64 +/- 0.42 mg/ml in the THA group, 1.07 +/- 0.28 mg/ml in the OA group, and 1.30 +/- 0.56 mg/ml in the ION group. The concentration of HA in the synovial fluid of the THA patients was significantly lower than that of the OA and ION patients (P = 0.0156 vs OA, P = 0.003 vs ION). The molecular weight of HA was 309 +/- 88.3 x 10(4) Da in the THA group, 377 +/- 201 x 10(4) Da in the OA group, and 240 +/- 148 x 10(4) Da in the ION group; these values do not differ significantly (P = 0.259 vs OA, P = 0.174 vs ION). Among the THA patients, there was no relation between the concentration of HA and the age of the patient, length of time since the first operation, or type of prosthesis fixation; there was also no relation between the molecular weight of HA and each of these factors. These results suggest that a pseudosynovial membrane is regenerated after THA, and that it produces HA of the same molecular weight as that in patients with OA and ION, although in smaller quantities.

Adult↗
PubMed2000

A (1-->3,6)-beta-d-galactosyl epitope containing uronic acids associated with bioactive pectins occurs in discrete cell wall domains in hypocotyl and root tissues of flax seedlings.

We have used a well-characterized antibody specific for an epitope consisting of (1-->3,6)-beta-d-galactosyl residues with terminal glucuronic or 4-O-methylglucuronic acids of a bioactive pectin and immunocytochemistry to investigate its secretion and wall distribution in the hypocotyl and root tissues of flax seedlings. Our results show that this antigenic epitope is associated with flax pectins and is expressed by all the cells of the hypocotyl and root tissues. In the hypocotyl, it is abundant in the primary wall of epidermal cells as well as in the secondary wall of fiber cells, and is relatively less abundant in parenchyma cell walls. In contrast, the epitope is not detected in the middle lamellae and cell junction regions. In the root tip cells, immunogold electron microscopy shows that the cell walls of peripheral, columella, meristematic, cortical, and epidermal cells contain significant amounts of this epitope and that the distribution patterns are distinct. Together, these findings show that the antigenic epitope occurs in discrete domains of the wall implying a strict spatial regulation of the epitope-containing molecules. The results also show that, in root cells, the epitope is present within Golgi cisternae and is predominantly assembled in the trans and the trans-Golgi network compartments.

Antibodies↗
PubMed2000

The Prr1 response regulator is essential for transcription of ste11+ and for sexual development in fission yeast.

Schizosaccharomyces pombe expresses a putative transcription factor, named Prr1, which is intriguing in the sense that it contains a bacterial type of phospho-accepting receiver domain, preceded by a mammalian heat shock factor (HSF2)-like DNA-binding domain. The receiver domain is most probably involved in an as yet unidentified histidine-to-aspartate (His-to-Asp) phosphorelay pathway in S. pombe. In this study, the structure, function, and cellular localization of Prr1 were assessed in the context of oxidative stress and His-to-Asp phosphorelay. As the most intriguing result of this study, we found that Prr1 is essential not only for the expression of genes induced by oxidative stress (e.g., ctt1+ and trr1+), but also for the expression of ste11+, which in turn is responsible for the expression of a variety of genes required for sexual development. Accordingly, Prr1-deficient cells are not only hypersensitive to oxidative stress, but also severely defective in conjugation and/or spore formation. These results suggested that the transcription factor Prr1 plays a pivotal role in an as yet unknown signal transduction pathway that is implicated in sexual differentiation. These findings are discussed with special reference to the well-characterized transcription factors Pap1 and Atf1 of S. pombe.

Activating Transcription Factor 1↗
PubMed2000

Pneumoperitoneum with carbon dioxide enhances liver metastases of cancer cells implanted into the portal vein in rabbits.

BACKGROUND: Little is known about the role of the CO2 pneumoperitoneum on tumor cells that spread from the portal system into the liver during laparoscopic surgery for gastrointestinal malignancies. Therefore, we designed a study to investigate the effect of CO2 pneumoperitoneum on cancer cells implanted in the portal vein in a rabbit model. METHODS: Immediately after intraportal inoculation of 2.5x10(5) cells of VX2 cancer, the rabbits received either CO2 pneumoperitoneum at a pressure of 10 mm Hg for 30 min (pneumoperitoneum group, n = 14) or laparotomy alone for 30 min (laparotomy group, n = 14). RESULTS: The number (p<0.01) and area of cancer nodules (p = 0.045) on the liver surface on day 17 were greater in the pneumoperitoneum group than in the laparotomy group. The frequency of cancer nodules >3.0 mm in diameter was higher in the pneumoperitoneum group than in the laparotomy group (p<0.001). CONCLUSIONS: Compared with laparotomy, CO2 pneumoperitoneum enhanced the development of liver metastases in this experimental model.

Animals↗
PubMed2000

Influence of trocar placement and CO(2) pneumoperitoneum on port site metastasis following laparoscopic tumor surgery.

BACKGROUND: The mechanisms involved in the development of port site metastasis following laparoscopic tumor surgery remain controversial. Therefore, we decided to investigate the influence of trocar placement and CO(2) pneumoperitoneum on abdominal wound implantation in relation to intraperitoneal tumor growth in a rabbit model. METHODS: Rabbits received either CO(2) pneumoperitoneum with insertion of nine trocars (pneumoperitoneum group, n = 15), insertion of nine trocars alone (nonpneumoperitoneum group, n = 15), or nine abdominal incisions (control group, n = 13) 3 days after intraperitoneal inoculation of VX(2) cancer cells. RESULTS: The frequency of overall wound implantation on day 17 in the pneumoperitoneum group (24.4%) and nonpneumoperitoneum group (27.4%) tended to be higher than that in the control group (15.3%) (p = 0. 06). There was no significant difference among the three groups in the growth of cancer nodules on the omentum. CONCLUSIONS: The presence of a trocar may be a factor contributing to port site metastasis but CO(2) pneumoperitoneum appears not to be a factor.

Animals↗
PubMed2000

Changes in liver fatty acid unsaturation after partial hepatectomy in the rat.

The purpose of this study was to assess changes in the degree of fatty acid unsaturation in rat liver after partial hepatectomy. This is the first study in which liver fatty acid unsaturation has been analyzed over a long period of regeneration until day 28 after operation. The relationship between changes in unsaturation and fatty acid composition in the regenerating liver were also investigated in this study. Proton nuclear magnetic resonance spectroscopy revealed significantly elevated levels of unsaturation with a maximum on day 5 after partial hepatectomy, compared with untreated controls (11.72+/-0.55 vs. 11.05+/-0.26%, P < 0.05). No significant changes in unsaturation were found in day 1 regenerating liver, which is rich in absolute amounts of fatty acids. Based on gas-liquid chromatography, the relative amounts of oleic acid (18:1n-9) and linoleic acid (LA; 18:2n-6) were increased, while polyunsaturated fatty acids such as arachidonic acid (20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) were decreased on day 1. On the other hand, on day 5 of regeneration, while most fatty acids were returning to their preoperative control levels, only DHA was higher than the control value (7.69+/-0.58 vs. 5.57+/-0.37%, P < 0.001). The high levels of unsaturation on day 5 were found to be partly due to the increase in DHA. The findings suggest that some significant signals are transmitted during the regeneration process owing to alterations in the membrane structure by the high levels of fatty acid unsaturation and the increase in DHA levels on day 5 after partial hepatectomy.

Animals↗
PubMed2000

Detection of left ventricular regional relaxation abnormalities and asynchrony in patients with hypertrophic cardiomyopathy with the use of tissue Doppler imaging.

BACKGROUND: It is well known that the distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with hypertrophic cardiomyopathy (HCM), which results in regional heterogeneity of LV early diastolic function. The advent of tissue Doppler imaging (TDI) has allowed the noninvasive evaluation of regional LV wall motion velocities. The aim of this study was to evaluate regional LV relaxation abnormalities and asynchrony noninvasively in patients with HCM by using pulsed and color-coded TDI. METHODS AND RESULTS: We studied 20 patients with asymmetric septal hypertrophy (HCM group) and 18 age-matched normal patients (control group). The peak early diastolic motion velocity (Ew) and time from the aortic component of the second heart sound to the peak of the Ew (II(A)-Ew) were measured by pulsed TDI. The myocardial velocity gradient during early diastole (MVG-Ew) also was measured by color-coded TDI. Mean values for these parameters were determined on the basis of measurements made at 2 sites of the ventricular septum or posterior wall at the levels of chordae tendineae and papillary muscles. The mean Ew and mean MVG-Ew for the ventricular septum and posterior wall were significantly lower, and mean II(A)-Ew was significantly prolonged in the HCM group compared with the control group. This difference was most pronounced in the hypertrophied ventricular septum of the HCM group. The standard deviations of II(A)-Ew for the ventricular septum and posterior wall were significantly greater in the HCM group than in the control group. The time constant of LV pressure decay during isovolumic diastole (tau) correlated inversely with Ew and MVG-Ew and correlated directly with II(A)-Ew. Furthermore, tau correlated directly with the standard deviation of the II(A)-Ew. CONCLUSIONS: LV early diastolic function in patients with HCM may be mediated by an augmentation of regional LV relaxation abnormalities and asynchrony.

Adult↗
PubMed2000

Photoreceptor-specific expression of platelet-derived growth factor-B results in traction retinal detachment.

Expression of platelet-derived growth factor (PDGF)-A and PDGF-B is increased in patients with proliferative retinopathies in which traction retinal detachments occur. Previous studies have demonstrated that increased expression of PDGF-A in the retina of transgenic mice results in retinal gliosis due to proliferation of astrocytes with different retinal phenotypes based on the time of onset and location of the PDGF-A production. In this study, we investigated the effects of PDGF-B in the retina using gain-of-function transgenic mice that express PDGF-B in photoreceptors. These mice show proliferation of astrocytes, pericytes, and, to a lesser extent, endothelial cells, resulting in ectopic cells on the surface and extending into the retina. The sheets of cells exert traction on the retina resulting in traction retinal detachments similar to those seen in humans with proliferative retinopathies. These studies suggest that PDGF-B has more dramatic effects in the retina than PDGF-A, because it acts on additional cell types, in particular on pericytes, which have a highly developed contractile apparatus. These studies in the retina suggest a means that could be used in other tissues throughout the body to achieve graded PDGF effects. They also provide a new model of traction retinal detachment that can be used to investigate new treatments for patients with proliferative retinopathies.

Animals↗
PubMed2000

Platelet-derived growth factor-A-induced retinal gliosis protects against ischemic retinopathy.

Retinal astrocytes are located in the nerve fiber layer and along retinal blood vessels and have been hypothesized to participate in the induction and maintenance of the blood-retinal barrier. Platelet-derived growth factor-A (PDGF-A) is normally produced by retinal ganglion cells and is involved in astrocyte recruitment and proliferation. We used gain-of-function transgenic mice that express PDGF-A in photoreceptors to explore the roles of PDGF-A and astrocytes in the retina. Transgene-positive mice developed glial infiltration of the inner retina and had significantly less oxygen-induced retinal vascular closure and no neovascularization compared with littermate controls, which had prominent vascular closure and neovascularization. The increased survival of endothelial cells in transgenic mice in the face of oxygen-induced down-regulation of vascular endothelial growth factor was accompanied by an increase in astrocyte-derived fibroblast growth factor-2. Therefore, PDGF-A increases retinal astrocytes, which promote the survival of endothelial cells as well as their expression of barrier characteristics.

Animals↗
PubMed2000

Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.

Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies.

Aging↗
PubMed2000

Somatic mutations of the APC gene in primary breast cancers.

APC gene mutations play an important role in the initiation step of colorectal carcinogenesis in both familial adenomatous polyposis (FAP) patients and non-FAP patients. Although the APC gene is expressed in most tissues, including the lung, liver, kidney, and mammary gland, its somatic mutations have rarely been found in primary tumors affecting these organs. We have developed a sensitive yeast-based assay for screening almost the entire coding region of the APC gene. By this method, we have been able to detect somatic mutations of the APC gene in 57% of colorectal cancers and none in non-small cell lung cancers. Interestingly, the assay detected somatic APC gene mutations in 18% of breast cancers, in which APC gene mutation was previously considered rare. In the breast cancers, most of the APC mutations were distributed outside the mutation cluster region that has been advocated for colorectal cancers. We also noted a difference in the mutation pattern of the APC between colorectal and breast cancers. In colorectal cancers, all base substitutions were observed at C residues (5 of 5), whereas in breast cancers the majority of them were found at G residues (4 of 5). Furthermore, APC mutations were observed at a significantly high frequency in advanced stages of primary breast cancers (TNM classification, P < 0.05; T category, P < 0.01). Our data suggest that the etiology of the APC mutations and their biological role in carcinogenesis may differ between colorectal and breast cancers.

Adenomatous Polyposis Coli↗
PubMed2000

Theoretical study of intracellular stress fiber orientation under cyclic deformation.

We studied stress fiber orientation under a wide range of uniaxial cyclic deformations. We devised and validated a hypothesis consisting of two parts, as follows: (1) a stress fiber aligns to avoid a mechanical stimulus in the fiber direction under cyclic deformation. This means that, among all allowable directions, a stress fiber aligns in the direction which minimizes the stimulus, i. e., the summation of the changes in length of the stress fiber over one stretch cycle; and (2) there is a limit in the sensitivity of the cellular response to the mechanical stimulus. Due to this sensing limit, the orientation angle in stress fibers is distributed around the angle corresponding to the minimum stimulus. To validate this hypothesis, we approximated an anisotropic deformation of the membrane on which cells were to be cultured. We then obtained the relationships between the stretch range and the fiber angle in the undeformed state which minimize the mechanical stimuli, assuming that the membrane on which stress fibers and cells adhered was homogeneous and incompressible. Numerical simulation results showed that the proposed hypothesis described our previous experimental results well and was consistent with the experimental results in the literature. The simulation results, taking account of the second part of the hypothesis with a small value for the limit in sensitivity to the mechanical stimulus, could explain why cell orientation is distributed so widely with cyclic stretch ranges of <10%. The proposed hypothesis can be applied to various types of deformation because the mechanical stimulus is always sensed and accumulates under cyclic deformation without the necessity of a reference state to measure the stimulus.

Animals↗