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Biomedical subjects

K Kaneda

Publications and source records attributed to K Kaneda.

At least 109 records · Page 6Linked to original sources

In vitro migratory potential of rat quiescent hepatic stellate cells and its augmentation by cell activation.

In liver injury, hepatic stellate cells are considered to depart from the sinusoidal wall and accumulate in the necrotic lesion through migration and proliferation. In this study, we investigated the migratory capacity of quiescent stellate cells in vitro and analyzed the relationship with proliferative response. Freshly isolated stellate cells that were seeded in the upper chamber of Cell Culture Insert (Becton Dickenson, Franklin Lakes, NJ) started to migrate to the lower chamber at 1 day and increased in migration index to 19% at 2 days. Cells in the lower chamber were stretched in shape with many lipid droplets and showed quiescent properties, i.e., negative expression of alpha-smooth muscle actin (alpha-SMA) or platelet-derived growth factor receptor-beta (PDGFR-beta). Migratory capacity in quiescent cells was also shown in the Matrigel-coated insert. Matrix metalloproteinase-2 (MMP-2) messenger RNA expression was low just after isolation, but was enhanced as migration became prominent. Migrating cells further showed higher proliferative activity than resting ones. The presence of PDGF/BB and Kupffer cells accelerated stellate cell migration by the chemotactic mechanism and concurrently augmented proliferation, whereas that of dexamethasone and interferon-gamma (IFN-gamma) attenuated migration as a result of general suppression effects. Compared with quiescent ones, alpha-SMA and PDGFR-beta-positive activated stellate cells obtained by 14-day culture exhibited more rapid and prominent migration, being regulated by mediators in a similar manner as described previously. These data indicate that quiescent stellate cells undergo migration, which is linked to proliferation and enhanced by PDGF/BB and Kupffer cells, suggesting the involvement of this function in the initial phase of development of postnecrotic fibrosis.

Actins↗

High expression of macrophage migration inhibitory factor in the synovial tissues of rheumatoid joints.

Macrophage migration inhibitory factor (MIF) plays an important role in inflammation and immunity via autocrine/paracrine and endocrine routes. We examined the presence of MIF in the synovial fluids of rheumatoid arthritis (RA) patients. The content of MIF in the synovial fluid was quantitated by enzyme-linked immunosorbent assay which revealed that the concentration of MIF for RA patients was 85. 7+/-35.2 ng/ml (mean+/-SD) (n=25). In comparison, the concentrations for osteoarthritis patients and normal volunteers were 19.5+/-5.3 ng/ml (n=12) and 10.4+/-1.1 ng/ml (n=5), respectively. The expression of MIF mRNA and presence of MIF protein in the synovial tissues of RA were demonstrated by Northern blot and Western blot analyses, respectively. Immunohistochemical analysis revealed that positive staining was largely observed in the cytoplasm of infiltrating T lymphocytes, which might be the major source of MIF detected in the synovial fluids. The pathophysiological role of MIF in RA remains to be elucidated; however, the present results for the first time suggest the possibility that MIF is involved in the potentiation of inflammatory and immunological responses in rheumatoid joints.

Arthritis, Rheumatoid↗

A double-masked multicenter comparative study between alendronate and alfacalcidol in Japanese patients with osteoporosis. The Alendronate Phase III Osteoporosis Treatment Research Group.

To evaluate the efficacy and safety of alendronate, a double-masked, active (alfacalcidol) controlled comparative study for 48 weeks was carried out in a total of 210 Japanese patients with osteoporosis. The doses of alendronate and alfacalcidol were 5 mg/day and 1 microgram/day, respectively. The lumbar bone mineral density (LBMD) values observed at 12, 24, 36 and 48 weeks after the initiation of alendronate treatment were 3.53 +/- 0.53%, 5.37 +/- 0.62%, 5.87 +/- 0.74% and 6.21 +/- 0.59% (mean +/- SE), respectively, higher than the baseline value. Corresponding values in the alfacalcidol group were 1.50 +/- 0.43%, 0.69 +/- 0.63%, 1.12 +/- 0.60% and 1.36 +/- 0. 63%, respectively. There was a significant difference between the two groups at each time point (p<0.05 or p<0.001). The bone turnover markers were depressed during treatment in the alendronate group: -32.2% for alkaline phosphatase, -53.7% for N-terminal osteocalcin and -45.0% for urinary deoxypyridinoline compared with the corresponding baseline values. On the contrary, no notable changes in these parameters were observed in the alfacalcidol group. Treatment with alendronate caused a transient decrease in serum calcium concentrations associated with an increase in the serum level of intact parathyroid hormone. In contrast, treatment with alfacalcidol resulted in a tendency of these parameters to change in the opposite direction. No difference in fracture incidence between the two groups was observed. The overall safety of alendronate was comparable to that of alfacalcidol. In conclusion, although it was a relatively short-term study of 48 weeks, the results of the present study indicate that alendronate at the daily dose of 5 mg was effective in increasing LBMD and that no serious drug-related adverse events were observed in the alendronate-treated patients. Alendronate is more efficacious than alfacalcidol in increasing bone mineral density, although the mechanisms of the actions of the two drugs are apparently different.

Aged↗

Induction of smooth muscle cells in the fibrous capsule of human hepatocellular carcinoma but not in the septa of hepatic cirrhosis.

We examined the expression of smooth muscle cytoskeleton in spindle-shaped cells in the capsule of hepatocellular carcinoma (HCC) and the septa of liver cirrhosis (LC). Serial sections of livers resected from 11 patients were stained with monoclonal antibodies against vimentin, desmin, smooth muscle actin (1A4, HHF35, CGA7) and smooth muscle myosin heavy chain isoforms (SM1, SM2). Capsular spindle-shaped cells exhibited a cytoskeletal feature indicative of intermediately differentiated smooth muscle cells. Computer-assisted morphometry revealed that the proportions of 1A4-, HHF35-, CGA7- and SM1- positive areas to vimentin-positive area were 88.0+/-11.0%, 50.8+/-17.4%, 25.3+/-16.4% and 19.4+/-12.4% (n=11) in main tumours and 86.6+/-9.4%, 50.9+/-18.7%, 21.1+/-12.3% and 17.6+/-9.7% (n=12) in daughter tumours, indicating that spindle-shaped cells are heterogeneous in cytoskeletal expression. Septal spindle-shaped cells in LC lacked the cytoskeletal proteins specific to differentiated smooth muscle cells (CGA7, SM1, SM2 and desmin). Electron microscopically, capsular spindle-shaped cells contained more microfilaments and less rough endoplasmic reticulum than do septal cells. Intermediately differentiated smooth muscle cells are induced in the capsule of HCC but not in the septa of LC, suggesting a role for stromal interaction by tumour cells in the induction of smooth muscle cells.

Actins↗

Localization and ultrastructure of pulmonary dendritic cells during delayed-type hypersensitivity reactions in mice.

Dendritic cells (DCs) are widely distributed in the airways and can serve as potent antigen-presenting cells. To clarify their involvement in the cell-mediated immune responses of the lung, we immunohistochemically investigated their distribution and kinetics during pulmonary delayed-type hypersensitivity (DTH) reactions induced in sensitized mice by intratracheal instillation of hapten. Cellular infiltrate appeared around the bronchiole and its accompanying blood vessel at 12 h after elicitation and progressively expanded by 48 h. As quantitated by computer-assisted morphometry, I-A(+) DCs and CD4(+) Th cells significantly increased in number around the bronchiole to a maximum at 24 h, whereas F4/80(+) macrophages were predominantly accumulated around the accompanying vessel with a peak at 48 h. Serial-section analysis revealed that DCs were colocalized with Th cells in the inflamed peribronchiolar tissue. Immunoelectron microscopy demonstrated that DCs found inside and around the capillaries and venules of peribronchiolar interstitium displayed round forms, indicating their emigration from here, while those situated far from the microvessels were elongated, often in close apposition to the lymphocytes. Mitosis of DCs was rarely seen. The present results suggest that peribronchiolar accumulation of DCs resulting from accelerated influx of blood-borne immature DCs and the interaction with T cells at the application site may play inducing roles in the development of pulmonary DTH reactions by enhancing the recruitment of macrophages.

Animals↗

The effects of wrist distraction on carpal kinematics.

Changes in carpal kinematics under wrist distraction were studied in fresh cadaveric specimens. A magnetic tracking device measured kinematic motions of the scaphoid, lunate, and third metacarpal relative to the fixed radius in 3 planes of passive motion (coronal, sagittal, and "dart throwers") under progressive distraction loads. The change in percent contribution of the radiocarpal and midcarpal joints was calculated. Radiocarpal motion during extension was decreased as increasing traction was applied, but it increased with flexion. Motion of the scaphoid relative to the lunate was smaller in the oblique plane, resulting in less radiocarpal motion than in the sagittal plane. In the coronal plane, traction had little effect on radial deviation, but ulnar angulation of the scaphoid was greater with ulnar deviation of the wrist. These results suggest that different degrees of tension exist in the palmar and dorsal ligaments with the wrist under traction and during different planes of wrist motion. If wrist motion is desired during fixed traction, such as used clinically with external fixation, the dart-throwers motion (wrist extension with radial deviation and wrist flexion with ulnar deviation) appears to have the least impact on radiocarpal motion. If greater radiocarpal motion is desired, however, such as during postoperative mobilization, flexion-extension and radioulnar deviation will create more radiocarpal motion than the dart-thrower's motion.

Biomechanical Phenomena↗

Noninvasive assessment of the cardiac baroreflex: response to downward tilting and comparison with the phenylephrine method.

OBJECTIVES: We studied the relation between changes in systolic blood pressure and RR interval during downward tilting in comparison with assessment of baroreflex sensitivity (BRS) measured by the phenylephrine method (Phe-BRS) and with measures of heart rate variability (HRV). BACKGROUND: The method most extensively used for assessing BRS involves bolus injections of phenylephrine. Several noninvasive methods proposed to assess BRS have not been widely applied in the clinical setting. METHODS: Sixteen healthy male volunteers were studied (mean age +/- SD 27.5+/-4.6 years). Arterial blood pressure using tonometry and electrocardiogram was simultaneously recorded. After 20 min of 70 degrees upright tilting, the table was returned to supine position at a speed of 3.2 degrees/s. Subsequently, BRS was assessed using an intravenous bolus injection of phenylephrine (2 to 3 microg/kg). Heart rate variability under resting conditions also was analyzed. RESULTS: In all subjects, a beat to beat systolic blood pressure increase associated with corresponding RR interval lengthening was observed during downward tilting as well as during phenylephrine administration. During both testing procedures, these two variables showed linear correlation, and the slope of regression line during downward tilting (DT-BRS) correlated significantly with Phe-BRS (r = 0.79, p = 0.0003). The DT- and Phe-BRS also correlated significantly with the high frequency component of resting HRV (r = 0.70, p = 0.0023 for DT-BRS; r = 0.58, p = 0.0185 for Phe-BRS). CONCLUSIONS: We conclude that in a small homogeneous group DT-BRS provided an assessment of reflex cardiac vagal function comparable to that obtained by the phenylephrine method.

Adult↗

In vivo activation of langerhans cells and dendritic epidermal T cells in the elicitation phase of murine contact hypersensitivity.

Langerhans cells (LCs) and dendritic epidermal T cells (DETCs) constitute the skin immune system. To demonstrate the kinetics of in vivo activation of murine LCs and DETCs in the elicitation phase of contact hypersensitivity, we measured the cell area positively stained for I-A and gammadeltaT-cell receptor (or Thy-1.2), respectively, under a fluorescence microscope at various time intervals after topical application of dinitrofluorobenzene. The fluorescence-positive area of LCs increased in parallel with that of DETCs at 1 h and 24 h, indicating the biphasic activation of LCs and DETCs. Early activation was hapten-specific and often exhibited close LC-to-DETC apposition. Experiments with in vivo administration of neutralizing anticytokine antibodies revealed that none of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta were involved in the induction of early activation of LCs and DETCs, while TNF-alpha and IL-1beta mediated late activation of LCs, and IFN-gamma and IL-1beta mediated that of DETCs. Our results indicate that LCs and DETCs are synchronously and biphasically activated in the epidermis during the elicitation phase of contact hypersensitivity and suggest that different mechanisms may control early and late activation.

Animals↗

Liver microvascular architecture: an insight into the pathophysiology of portal hypertension.

Structural adaptations in the liver to constantly receive and release a large volume of circulating blood at low pressure are present at many levels; alteration of these structures can modify flow and perturb pressure gradients. Liver growth multiplies the lobule number by a factor of 4-5 after birth. Lobule configuration conforms with observations in space division, each unit being bordered by planes; curvature will impede expansibility and retractability among units. Lobular organization with hepatocytic plates and sinusoids, being radial centrally and reticular peripherally, maximizes its reversible distensibility. Resistance sites in the portal, sinusoidal, and hepatic system are subject to species variations; real portal sphincters are photographed in the frog. Small venules are demonstrably resistive. In endothelin-1-induced rat portal hypertension, the distal segment of preterminal portal venules constricts most intensely, whereas the terminal portal venules and sinusoids are flaccid. Their pericytes and arachnocytes (stellate cells, Ito cells, retinol-storing cells), respectively, possess no effective contractile machinery. In the dog, the initial sublobular veins react with venoconstriction to many stimulations. Well-developed musculature in hepatic veins, as in man and pig, can regulate flow by junctional constriction. These histoarchitectonics provide hepatic hemodynamics with high capacitance and high compliance properties. The hepatic artery supplies oxygenated blood to five stromal compartments: peribiliary vascular plexus, portal tract interstitium, portal vein vasa vasorum, hepatic capsule, and central-sublobular-hepatic vein vasa vasorum. Its role as the nutrient vessel to the veins is established, but what influence it may have in the pathophysiology of portal hypertension awaits clarification.

Animals↗

Growth factor-induced expression of macrophage migration inhibitory factor in osteoblasts: relevance to the plasminogen activator system.

Macrophage migration inhibitory factor (MIF) is a cytokine that mediates inflammatory processes in a variety of tissues. In this study, we examined the expression of MIF mRNA in the mouse osteoblastic cell line MC3T3-E1, whose proliferation is promoted by various growth factors. In the subconfluent state, transforming growth factor-beta, basic fibroblast growth factor, insulin-like growth factor-II, and fetal calf serum markedly upregulated MIF mRNA expression. The upregulation of MIF mRNA was less extensive when the cells were stimulated by the same growth factors in the overconfluent state. We also investigated the expression of MIF mRNA through a whole cell cycle from G0 phase when the osteoblastic cells were synchronized by serum starvation. The MIF mRNA expression, which gradually increased from the G0 and reached its maximum at the S phase, was nonperiodic. Moreover, human recombinant MIF upregulated the expression of urokinase plasminogen activator inhibitor-1 (PAI-1) precursor mRNA in human osteoblastic Saos-2 cells. Plasminogen activator (PA) is known to play an important role in bone metabolism, for example, in activation of procollagenase or growth factors indirectly via the formation of plasmin, and in mitogenic activity for osteoblastic cells. Our results suggest that MIF modulates the proliferation of osteoblasts and, moreover, bone tissue remodeling through the PA and plasmin system.

Animals↗

Abasic site recognition mechanism by the Escherichia coli exonuclease III.

In order to elucidate the mechanism of AP site recognition by Echerichia coli exonuclease III (exoIII), site-directed mutagenesis of the Tyr109, the Trp212, and the Phe213 residues, which were conserved in the type II AP endonuclease from various organisms and located in the vicinity of the catalytic site, was performed. The exoIII-W212S mutant lacked any detectable AP endonuclease activity and binding ability to the duplex DNA containing an AP site, while the exoIII-Y109S and exoIII-F213W mutants retained a low level of activities (13% and 83%, respectively, compared with wild-type exoIII). This study suggests that the Trp212 is an important component for abasic site recognition by the E. coli exonuclease III.

Amino Acid Substitution↗

Biomechanical studies of the rabbit patellar tendon after removal of its one-fourth or a half.

Effects of the overstressing induced by the harvest of grafts from the patellar tendon on the mechanical properties and morphometry of remaining tendon were studied using a rabbit model. The width of the patellar tendon was reduced by one-fourth or one-half equally removing the medial and lateral portions; by this surgery, the cross-sectional area was decreased by 25 or 50 percent from the original area. After all the rabbits were allowed unrestricted activities in cages for 3 to 12 weeks, their patellar tendons were harvested for mechanical and histological studies. The one-fourth removal induced no significant changes in the mechanical properties, but significantly increased the cross-sectional area. In the case of one-half removal, tensile strength and tangent modulus did not change in some tendons, although the cross-sectional area increased significantly. In the other central half tendons, mechanical strength decreased markedly, while the cross-sectional area increased; hypercellular areas and breakage of collagen bundles were observed in these tendons. These results indicate that the patellar tendon has an ability of functionally adapting to overstressing by changing the cross-sectional area, while keeping the mechanical properties unchanged, if the extent of overstressing is less than 30 percent.

Animals↗

Osteonecrosis of the femoral head. Simple varus intertrochanteric osteotomy.

We present the long-term results of simple varus intertrochanteric osteotomy for osteonecrosis of the femoral head. We followed 26 hips in 20 patients, with a mean age at the time of surgery of 36 years, for a mean of 12.5 years. The mean varus angulation was 23 degrees. The outcome in 19 of the hips (73%) was good or excellent; seven (27%) had a fair or poor result, with four needing some form of prosthetic arthroplasty. Simple varus intertrochanteric osteotomy is indicated, even if the extent of the capital infarct comprises more than 50% of the diameter of maximum radial distance from the circumference, provided that after operation the medial necrotic lesion measures less than two-thirds of the weight-bearing area, and the superolateral bone is normal.

Adult↗

Changes in the orientation of collagen fibers on the superficial layer of the mouse tibial bone after denervation: scanning electron microscopic observations.

This study was undertaken to evaluate the relationship between the mechanical stress loaded onto the bone and the orientation of collagen fibers formed by osteoblasts. The femoral, obturator, and sciatic nerves in the left posterior legs of 7-week-old mice were exposed and electroscissored to reduce the mechanical stress loaded onto the leg. Four weeks after operation, the tibial bones in the control and denervated legs were removed and observed by scanning electron microscopy (SEM) after NaOCl treatment. In the control right tibia, collagen fibers on the superficial bone matrix tended to be arranged parallel to the longitudinal axis of the bone. However, the arrangement of collagen fibers in the left tibia, which were immobilized for 4 weeks by denervation, was disorganized and ran in random directions. The findings suggest that the direction of collagen fibers in the bone changes in response to the mechanical stress loaded onto the bone, probably due to changes in the activity of osteoblasts in the denervated leg.

Animals↗

Phenotypical and morphological alterations to rat sinusoidal endothelial cells in arterialized livers after portal branch ligation.

The hepatic sinusoids are preferentially supplied with portal venous blood and equipped with fenestrated endothelial cells that are distinct from capillary endothelial cells. We previously observed in rats that sinusoidal capillarization proceeded concurrently with arterial blood supply during hepatocarcinogenesis. This study aimed to clarify the inducing role of arterialization in sinusoidal capillarization by investigating phenotypical, morphological and functional alterations to sinusoidal endothelial cells (SECs) in arterialized rat livers induced by portal branch ligation. At one week, after massive hepatic necrosis following ligation, the livers were restored to their normal architecture without causing post-necrotic fibrosis. At 12-21 weeks, they exhibited a normal histology except for mild pericellular fibrosis which developed along sinusoids or between adjacent hepatocytes. SECs expressed factor VIII-related antigen and showed a decrease in the number of fenestrae and porosity, still lacking any basement membrane but further retaining the functional capacity for carmine dye uptake. Stellate cells, while occasionally associated with large amounts of collagen bundles, contained many lipid droplets and expressed no alpha-smooth muscle actin, indicating a quiescent property. Kupffer cells were commonly found within the sinusoids. The present results indicate that arterialization of the liver induces a partial (but not complete) transition of SECs into capillary-type endothelial cells, suggesting that arterialization might be one of the factors which induce sinusoidal capillarization in the development of hepatocellular carcinoma.

Animals↗

One-stage posterior decompression and reconstruction of the cervical spine by using pedicle screw fixation systems.

OBJECT: This retrospective study was conducted to analyze the results of one-stage posterior decompression and reconstruction of the cervical spine by using pedicle screw fixation systems in 46 patients. METHODS: Causes of cervical myelopathy in these 46 patients included spondylosis or ossification of the posterior longitudinal ligament, rheumatoid arthritis, metastatic or primary vertebral tumors, cervical spinal injuries, and spinal cord tumor. Thirty-three patients underwent this one-stage procedure as primary surgery. In the remaining 13 patients who had previously undergone laminectomies, the one-stage procedure was performed as salvage surgery. Cervical pedicle screws were inserted into the pedicles after probing and tapping. Graft bone was placed on the bilateral lateral masses, and pedicle screws were interconnected longitudinally by either plates or rods. Postoperatively, 26 patients showed improved neurological status (at least one grade improvement on Frankel's functional classification). There were no cases of neurological deterioration postoperatively. Solid bony fusion was obtained in all patients, except in seven patients with metastatic tumor who did not receive bone grafts. Correction of kyphosis was satisfactory. Postoperative radiological evaluation revealed that 10 (5.3%) of 190 screws inserted into the cervical vertebrae had perforated the cortex of the pedicles; however, no neurovascular complications were caused by the perforations. CONCLUSIONS: The pedicle screw fixation procedure, which does not require the lamina to be used as a stabilizing anchor, has proven to be valuable when performing one-stage posterior decompressive and reconstructive surgery in the cervical spine. The risk to neurovascular structures in this procedure, however, cannot be completely eliminated. Thorough knowledge of local anatomy and application of established surgical techniques are essential for this procedure.

Adult↗

[Surgical treatment of the Palmaz-Schatz stent trapped in the left coronary ostium].

A 72-year-old male with failed delivery of the Palmaz-Schatz stent to the coronary dissection following percutaneous transluminal coronary angioplasty (PTCA) was admitted to our hospital. He was very sick and required an emergent surgical procedures. We successfully carried out the bypass grafting to the LAD and removed the stent through the aortotomy. Besides his respiratory care, postoperative course was uneventful.

Aged↗

[Surgical treatment of acute massive pulmonary embolism: report of two cases].

We experienced two cases of acute massive pulmonary embolism. Both of the patients required emergent surgical procedures under cardiopulmonary bypass after cardiopulmonary resuscitation. Postoperative courses of them were uneventful. In severe cases with acute massive pulmonary thrombosis, there is no time to choose medical treatment alternative to pulmonary embolectomy. The diagnosis should be made promptly, and immediate decision of operation is very important.

Acute Disease↗