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Biomedical subjects

K Kaneda

Publications and source records attributed to K Kaneda.

At least 73 records · Page 4Linked to original sources

Expression of vascular endothelial growth factor by granulated metrial gland cells in pregnant murine uteri.

Granulated metrial gland (GMG) cells are a characteristic uterine component belonging to a natural killer cell lineage. This study is aimed at revealing their kinetic and spatial relationship with vascular growth during pregnancy and the expression of vascular endothelial growth factor (VEGF). GMG cells and blood vessels were identified by periodic-acid-Schiff-reagent (PAS)-stained granules and positive staining for factor-VIII-related antigen, respectively. GMG cells were widely distributed in the decidua and metrial gland and showed a numerical increase with a peak at day 13 in parallel with the increase of vascular density. Preceding the maximal vascular development at day 13, microvessels with a narrow lumen representative of neovascularization prevailed at days 7-9, and the VEGF content in the decidua/metrial gland was significantly elevated at days 7-13 concurrently with mRNA expression. By immunolight microscopy combined with PAS staining, GMG cells with PAS-stained granules were positive for VEGF. Immunoelectron microscopy demonstrated that immunoreactions were diffuse in the cytoplasm but not localized in the granules. In contrast, fibroblast-like stromal cells were negative. These data indicate that GMG cells express VEGF and may play inducing roles in uterine neovascularization during pregnancy.

Animals↗

Clinicopathological characterization of prion: a novel marker of activated human hepatic stellate cells.

BACKGROUND/AIMS: We recently demonstrated prion as a new marker for hepatic stellate cell activation in rats. Here, we have examined prion expression in normal and diseased human livers. METHODS: Prion expression was examined at protein level by immunohistochemistry and at mRNA level by in situ hybridization. RESULTS: While normal livers were negative for prion, all liver specimens but one from patients with chronic liver disease were positively stained. In chronic hepatitis, prion protein expression was found not only in the sinusoidal lining cells within the lobules but also in mesenchymal cells in expanded portal tracts. In alcoholic liver disease, prion-positive cells were found mainly in the areas of alcoholic hepatitis. Immunoelectronmicroscopy revealed that prion-positive cells were activated stellate cells. In situ hybridization demonstrated that the distribution of prion mRNA is similar to that of prion protein. In chronic hepatitis, the number of prion-positive cells correlated with the grade of activity but not with the stage of fibrosis. In alcoholic liver disease, levels of prion protein expression were significantly increased in the presence of alcoholic hepatitis. CONCLUSION: Prion as a novel marker of activated stellate cells correlates well with disease activity in human chronic liver diseases.

Biomarkers↗

Interference screw fixation of doubled flexor tendon graft in anterior cruciate ligament reconstruction - biomechanical evaluation with cyclic elongation.

OBJECTIVE: To biomechanically evaluate interference screw fixation of the doubled flexor tendon graft in anterior cruciate ligament reconstruction using cyclic elongation. DESIGN: Biomechanical properties of the interference screw fixation of the flexor tendons were compared with those of three standard fixation techniques which had been commonly performed in anterior cruciate ligament reconstruction. BACKGROUND: The interference screw fixation of the flexor tendon graft has attracted notice because of various possible advantages. METHODS: Forty fresh frozen porcine hind limbs were divided into four groups of ten knees each. Anterior cruciate ligament reconstruction was carried out in each group using one of four different procedures. For each group, five femur-graft-tibia complexes underwent submaximal cyclic elongation of 5000 cycles after initial tension of 80 N was applied. Then, tensile testing was performed in the same manner for the complex with a tensile tester. The remaining five complexes were examined in the same tensile test without applying any cyclic elongation. RESULTS: The initial tension was more rapidly relaxed by cyclic elongation in the flexor tendon graft fixed with interference screws than in the bone-patellar tendon-bone graft fixed with two standard techniques. After cyclic elongation, while the ultimate failure load of the former was significantly lower than the latter, the linear stiffness of the former was significantly higher than the flexor tendon graft fixed with sutures. CONCLUSION: The present study has clarified that the advantage of the interference fixation for the doubled flexor tendon graft is the high linear stiffness of the FGT complex, and the disadvantage of this screw is the low ultimate failure load of the FGT complex. RELEVANCE: The present study has suggested that vigorous activities should not be permitted for the patients in the early period after anterior cruciate ligament reconstruction using this fixation technique, because of its low ultimate failure load.

Animals↗

Reduction of polyethylene wear by concave dimples on the frictional surface in artificial hip joints.

For the purpose of reduction of polyethylene wear generated in artificial hip joints, concave dimples were formed on the surface of the metal femoral head by electrical discharge etching with the constant diameter of 0.5 mm, pitch of 1.2 mm, and depth of 0.1 mm. Using a hip joint simulator, the total amount of polyethylene wear was 7.2 mg in the concave-patterned condition and 23.1 mg in the nonpatterned condition. The reasons for the reduction of polyethylene wear by the concave pattern may be i) a reduction of abrasive wear by providing escape dimples for wear particles and ii) an improvement in the lubricity on the frictional surface by the supply of lubricant that is stored in dimples.

Friction↗

Decreased plasma levels of fibronectin in amyotrophic lateral sclerosis.

OBJECTIVES: Fibronectin (FN) possesses a wide range of biological functions. However, the role of plasma FN in vivo has not yet been established and there have been no published studies of plasma FN in ALS. The aim of this study was to measure plasma FN in ALS patients. MATERIAL AND METHODS: We measured plasma FN levels in 28 ALS patients, 18 control subjects with other neurologic or muscular diseases (control group A) and 21 healthy adults (control group B). The age and sex distributions among the 3 groups were comparable. RESULTS: Plasma FN levels were significantly lower in ALS patients than in control groups A and B. There was also a significant negative correlation between plasma FN levels and duration of illness in ALS patients. CONCLUSION: These data suggest that a metabolic alteration of FN may take place in ALS and that the measurement of plasma FN may serve as an indicator of clinical progression of this disorder.

Amyotrophic Lateral Sclerosis↗

Preventive effect of preoperative portal vein ligation on endotoxin-induced hepatic failure in hepatectomized rats is associated with reduced tumour necrosis factor alpha production.

BACKGROUND: Preoperative portal vein embolization successfully reduces the incidence of postoperative hepatic failure in which endotoxin is postulated to be involved. To identify the mechanism of this preventive effect, the relationship of endotoxin-induced liver injury with tumour necrosis factor (TNF) alpha and nitric oxide production in the peripheral blood, liver and spleen of rats subjected to preoperative portal vein branch ligation (PVL) was compared with that in rats undergoing sham operation. METHODS: Rats with PVL and those that underwent sham operation were subjected to resection of ligated liver lobes (PVL-Hx rats) and two-thirds hepatectomy (noPVL-Hx rats) respectively at day 5, followed by intravenous administration of endotoxin 200 microgram/kg body-weight at day 7. At various time intervals after endotoxin injection, the peripheral blood, liver and spleen tissues were harvested and analysed for TNF-alpha and nitric oxide production. RESULTS: The survival rates of noPVL-Hx and PVL-Hx rats at 48 h after endotoxin administration were 40 and 100 per cent respectively. The former rats showed more extensive liver injury as represented by higher serum aminotransferase and hyaluronate levels than the latter. Plasma concentrations of TNF-alpha at 1.5 h after endotoxin treatment were significantly higher in noPVL-Hx rats (mean(s.e.m.) 22 125(2175) pg/ml; n = 6) than PVL-Hx rats (8344(4076) pg/ml; n = 6) (P < 0.01). Consistent with this, expression of TNF-alpha messenger RNA in the liver and spleen was suppressed in PVL-Hx rats. In two-thirds hepatectomized rats, plasma TNF-alpha concentrations after endotoxin administration at 1, 2 and 3 days (14 350(2186), 26 375(2478) and 23 000(3745) pg/ml respectively; n = 6 each) were significantly higher than that before operation (9067(1559) pg/ml; n = 6) (P < 0.05), whereas those at 5 and 7 days (10 102(3616) and 8580(1427) pg/ml respectively; n = 6 each) showed no significant increase. Furthermore, nitric oxide production in peripheral blood and liver was suppressed by preoperative PVL. CONCLUSION: Prevention of endotoxin-induced liver failure by preoperative PVL is associated with reduced production of TNF-alpha in the later phase of liver regeneration.

Animals↗

Ultrastructure of early phase hepatic metastasis of human colon carcinoma cells with special reference to desmosomal junctions with hepatocytes.

To demonstrate ultrastructural events in the early phase of hepatic metastasis of human colon carcinoma, we intrasplenically injected a highly metastasizable, human colon carcinoma cell line LM-H3 (1 x 10(6) cells) into nude mice, and electron microscopically investigated the hepatic metastasis. At 24 h, tumor cells adhered to the endothelial wall of terminal portal venules and periportal sinusoids. At 48-72 h, after extravasation, they deeply invaded the hepatic cell plate and the interstitial tissue of the portal tract, in which they underwent proliferation and made the metastatic foci. Tumor cells were linked with each other or with surrounding hepatocytes by desmosomes. Desmosomes were maintained during the mitosis. When invading tumor cells were exposed to the bile canaliculi, they generated microvilli on the surface. Microvilli were also formed at the luminal surface of intracytoplasmic inclusions. In the interstitial tissue of the portal tract, tumor cells were closely associated with fibroblasts. However, no junctional specializations were seen between them. The present study demonstrated that human colon carcinoma cell line LM-H3 formed desmosomes with hepatocytes soon after invasion of the hepatic cell plate, suggesting the regulatory role of an interaction with hepatocytes in the growth of metastatic foci within the liver parenchyma.

Animals↗

Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats.

Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP-470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl(4))- and dimethylnitrosamine-induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP-470. In CCl(4)-induced fibrosis, factor VIII-related antigen-positive blood vessels, desmin-, or alpha-smooth muscle actin (alphaSMA)-positive mesenchymal cells, bromodeoxyuridine (BrdU)-positive mesenchymal cells also decreased in number by treatment with TNP-470. In in vitro experiments, a supplement of 1,000 ng/mL TNP-470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet-derived growth factor (PDGF). Expression of HSC activation markers, i.e., alphaSMA and PDGF receptor beta, was also suppressed. The present results indicate that TNP-470 inhibits HSC proliferation by blocking the cell-cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect.

Actins↗

Unresponsiveness of intrahepatic lymphocytes to bacterial superantigen: rapid development of suppressive Mac-1(high) cells in the mouse liver.

We previously found that a small dose (2 microg per mouse) of staphylococcal enterotoxin B (SEB) induced early emerging unresponsiveness in intrahepatic-lymphocyte populations (IHLs). The purpose of this study was to reveal the inducing role of accessory cells involved in IHLs in this phenomenon. IHLs prepared at 3 to 24 hours after SEB injection failed to proliferate in response not only to SEB but also to SEA, representing ligand-nonspecific unresponsiveness, whereas spleen cells (SPCs) and mesenteric lymph-node cells showed transient proliferation. Unresponsiveness in IHLs was related to a deficit of their accessory cell function as measured by coculture of irradiated IHLs and antigen-specific, type 1 T-helper (Th1) clone cells. High levels of nitrite were detected in the culture supernatant. Supplement of N(G)-monomethyl-L-arginine lowered nitrite levels and concurrently restored the proliferative response of Th1 cells, indicating the involvement of nitric oxide in suppression. Adherent cells prepared from IHLs well reproduced these results. As shown by flow cytometry, Mac-1(high) Ia(+) cells, which mainly included F4/80(+) cells (macrophages) and a minor population of CD11c(+) cells (dendritic cells), increased in proportion in IHLs but not in SPCs at 6 to 24 hours. Depletion of Mac-1(high) cells from IHLs with antibody-coated magnetic beads recovered the proliferative response. Depleted Mac-1(high) cells had a monocytoid appearance. In immunostained sections, Kupffer cells came to highly express both Mac-1 and Ia at 12 hours. These results indicate that Mac-1(high)Ia(+) adherent cells, largely Kupffer cells activated by SEB, nonspecifically suppress the proliferation of Th1 cells via nitric oxide production before manifestation of ligand-specific unresponsiveness.

Animals↗

Force distribution through the wrist joint in patients with different stages of Kienböck's disease: using computed tomography osteoabsorptiometry.

The pattern of subchondral bone density has been considered to reflect the stress distribution that occurs under physiologic loading conditions. To determine the force distribution through the wrist joint with Kienböck's disease in living subjects, we applied a computed tomography osteoabsorptiometry and investigated the subchondral bone density pattern across the radio-carpal joint of 6 normal subjects and 10 patients suffering from Kienböck's disease (Lichtman's stage IIIA, 5 patients; stage IIIB, 5 patients). A single density maximum was found in each scaphoid and lunate fossa in all normal subjects. Among the subjects with Kienböck's disease, the current analysis demonstrated that the density maximum area significantly increased in the scaphoid fossa and decreased in the lunate fossa from stage IIIA to IIIB group. These findings indicate that the load is shifted away from the lunate to the scaphoid with the progression of Kienböck's disease in living subjects.

Absorptiometry, Photon↗

Experimental study of vascularized bone grafts: hypertrophy of the grafted bone.

The mechanism underlying hypertrophy of experimentally vascularized bone grafts was studied in 15-week-old rats. The segmental ulna was grafted to the tibial defect with an external fixator. In experiment 1, 24 rats were classified into four groups to evaluate conventional (non-vascularized), cuff (periosteum-encased, non-vascularized), and vascularized bone grafts, and vascularized segmental grafts with fracture. In experiment 2, 12 rats were classified into two groups according to the presence of mechanical loading. This involved vascularized bone grafts with external fixators, and vascularized bone grafts with external fixators removed after bone union. The bone dynamics of the grafts were investigated by several methods, including roentgenographic analysis, histologic studies, and fluorochrome labeling. In experiment 1, a slight bone formation was recognized in the conventional bone graft, while irregular bone formation with creeping substitution was observed in the cuff graft. The vascularized bone graft showed significant hypertrophy; hypertrophy of the vascularized bone with fracture was greater than that without fracture. In experiment 2, markedly circumferential bone formation was observed after removal of the external fixator, while slight new bone formation was observed during the late postoperative period in bone with an external fixator. These results suggest that hypertrophy can be promoted by artificial fracture of the grafted bone, and that mechanical loading is an important factor for remodeling of grafted bone.

Animals↗

Bipolar hemiarthroplasty for osteonecrosis of the femoral head. A 7- to 18-year followup.

This study evaluated clinical and radiographic results of bipolar hemiarthroplasties for the treatment of osteonecrosis of the femoral head. Forty-eight hips in 35 patients with a mean age of 37 years who underwent primary bipolar hemiarthroplasties were observed for an average of 11.4 years. Osteonecrosis was associated with corticosteroid use (21 patients), alcohol (six patients), idiopathic (four patients), and other conditions (four patients). The average Harris hip score was 46 before surgery and 86 at the time of the final followup. Twenty (42%) hips were radiographic failures, and 12 (25%) hips were revised. Groin symptoms were present in 20 (42%) hips. Radiographic proximal migration greater than 4 mm and osteoarthritic signs of the acetabulum indicated a high risk of groin symptoms. The results were inferior to those previously reported for total hip arthroplasty. Thus, for the treatment of osteonecrosis of the femoral head in which necrotic lesions are wide, the authors no longer use this system and currently use total hip arthroplasty.

Adult↗

Progression of joint arthrosis 10 to 15 years after high tibial osteotomy.

Forty-eight knees in 44 patients who had a high tibial osteotomy performed for medial compartment osteoarthritis were reevaluated twice, once at 1 year after surgery and again at 10 to 15 years after the high tibial osteotomy, to determine the effects of high tibial osteotomy on progression of medial and lateral joint arthrosis. Radiologically, although arthrosis significantly increased in the medial and the lateral joint compartment, there was no significant difference in the degree of progression between the two compartments. There was a significant correlation between the progression of medial joint arthrosis evaluated at 10 years or more after surgery and the femorotibial angle measured at 1 year. There was no significant correlation between the progression of lateral joint arthrosis in 10 to 15 years and the femorotibial angle measured at 1 year. The average knee function score improved significantly from 59.1 +/- 5.5 points before surgery to 85.1 +/- 6.1 points at the 1-year followup. At the final followup, the clinical score (80.7 +/- 5.4) had deteriorated relative to the 1-year results but still was significantly better than the preoperative score. The current results indicate that the greater the surgical valgus correction, the slower the progression of medial joint arthrosis. Lateral joint arthrosis did not progress more quickly after high tibial osteotomy, even if an overcorrection was performed.

Aged↗

In vivo and in vitro interactions between human colon carcinoma cells and hepatic stellate cells.

Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM-H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed alpha-smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM-H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture-induced activation contained platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta, and could augment LM-H3-cell proliferation and migration. Neutralizing antibodies against PDGF-AA and PDGF-BB and those against PDGF-BB and HGF inhibited proliferation and migration, respectively, of LM-H3 cells, whereas antibody against TGF-beta had no effect. LM-H3 cells expressed PDGF receptors-alpha and -beta and c-met. Conditioned medium of LM-H3 cells contained PDGF-AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti-PDGF-AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis.

Adenocarcinoma↗

Trehalose 6,6'-dimycolate (Cord factor) enhances neovascularization through vascular endothelial growth factor production by neutrophils and macrophages.

Trehalose 6,6'-dimycolate (TDM) plays important roles in the development of granulomatous inflammation during infection with Mycobacterium spp., Rhodococcus spp., etc. To reveal the augmenting effect of TDM on vascular endothelial growth factor (VEGF) production and neovascularization, we investigated murine granulomatous tissue air pouches induced by Rhodococcus sp. strain 4306 TDM dissolved in Freund's incomplete adjuvant (FIA), comparing them to pouches treated with FIA alone. Histologically, granulomatous tissue and new vessel formation, which reached a maximum at day 7, was greatly enhanced by treatment with TDM. At day 1, VEGF-positive neutrophils accumulated in the pouch wall with frequency of 95% of total infiltrating cells, adhering to TDM-containing micelles. By day 3, granulomatous tissue and new vessels started to develop, and VEGF-positive macrophages appeared in a small number and gradually increased in number thereafter. The pouch contents of VEGF, interleukin-1beta, tumor necrosis factor alpha, and transforming growth factor beta were significantly elevated in TDM-treated pouches, with peaks at days 1, 0.5, 1, and 3, respectively, compared to those of control pouches, while that of basic fibroblast growth factor showed no significant increase. Treatment with anti-VEGF antibody inhibited TDM-induced granulomatous tissue formation and neovascularization, and administration of recombinant VEGF into pouches treated with FIA alone induced neovascularization comparable to that in the TDM-treated pouches. Incubation of neutrophils and macrophages on TDM-coated plastic dishes increased the VEGF release. The present results indicate that TDM augments VEGF production by neutrophils and macrophages and induces neovascularization in the granulomatous tissue.

Animals↗

Purification and some properties of an aminopeptidase from the seeds of Cannabis sativa.

An aminopeptidase (HSA) with a molecular mass of 78 kDa was purified from hemp (Cannabis sativa) seeds. The activity was inhibited by monoiodeacetic acid, p-chloromercuri-phenylsulfonic acid, and Zn2+ ion. The specificity of HSA was similar to that of a leucyl aminopeptidase [EC 3.4.11.1] from mammalian cytosol. However, other enzyme properties were different from these of leucyl aminopeptidase.

Aminopeptidases↗

An epidemiologic study of occupational low back pain in truck drivers.

The factors in volved in occupational low back pain occurring in professional drivers were investigated epidemiologically with questionnaires (92 items) including low back symptoms, personal factors and occupational factors. The responses of one hundred fifty-three of one hundred eighty-one truck drivers who work in a large chemical industry corporation were analyzed after they had completely filled in questionnaires. As analysis of the results shows, the prevalence of LBP in one month of the survey was 50.3%. Correlating among data of personal factors and LBP, the prevalence of LBP was significantly higher in the drivers (Odd's ratio of 2.7) who answered "yes" to the item "shortage of spending time with family than in the drivers who didnt answer "yes. The occupational factors, working load and working environment showed no correlation with the prevalence of LBP. In contrast, 3 items of the working format related significantly to the prevalence of LBP: "irregular duty time (Odd's ratio of 3.0), "short resting time (2.4), and "long driving time in a day (2.0). Eighty-one of the 153 drivers (52.9%) pointed out the relationship between LBP and work, especially work which muolves vibration or road shock. Our results and the results from previous published studies suggested that vibration is an obvious risk factor for LBP. From the viewpoint of prophylaxis, an improvement in working conditions reduces the incidence of drivers' LBP to some extent.

Adult↗