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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 55 records · Page 3Linked to original sources

Ubiquitin expression in skin wounds and its application to forensic wound age determination.

The time-dependent expression of ubiquitin (Ub) was examined in murine skin wounds and 55 human skin wounds with different wound ages (groups I: 0-12 h, II: 1-5 days, III: 7-14 days and IV: 17-21 days). In murine skin wound specimens, neutrophils, macrophages and fibroblasts showed intensive Ub-positive reactions in the nuclei. In the human wound specimens with wound ages between 4 h and 1 day, neutrophils with strong intranuclear positive reactions for Ub were observed. With increasing wound ages, the nuclei of macrophages and fibroblasts were more intensively stained with anti-Ub antibody. Morphometrically, the intranuclear Ub-positive ratios were very low in group I. The skin wound specimens in groups II and IV showed Ub-positive ratios of >10%, and all samples in group III had Ub-positive ratios of >20%. These results suggest that a ratio of >10% for Ub indicates a wound age of at least 1 day. In contrast, Ub-positive ratios of less than 10% indicate a wound age of <1 day. Moreover, there was a significant difference in the Ub-positive ratio between group III and the other three groups. Thus, Ub-positive ratios considerably exceeding 30%, possibly indicate a wound age of 7-14 days. From the viewpoint of a forensic pathology application, the present study showed that Ub is suitable as a marker of wound age determination.

Adolescent↗

Pneumococcal purulent genual arthritis after allogeneic bone marrow transplantation.

A 21-year-old male patient with non-Hodgkin's lymphoma (diffuse large T-cell type, clinical stage IV) received allogeneic bone marrow transplantation (BMT) from a partially HLA-mismatched unrelated donor in July 1998 and achieved complete remission. Thereafter, he suffered from chronic graft-versus-host disease (GVHD) and was continuously administered immunosuppressive drugs for a long time. Two years after the BMT, he complained of severe pain in the right knee, which was swollen, and was diagnosed as having pneumococcal purulent genual arthritis. He underwent arthroscopic synovectomy and was administered systemic and intra-articular antibiotics, leading to a gradual improvement. Streptococcal infections are often seen in patients in the late phase after allogeneic BMT because of immunodeficiency associated with chronic GVHD and hyposplenism. Most streptococcal infections are respiratory tract infections and septicemia, and there have been very few reports on cases of purulent genual arthritis. Administration of prophylactic antibiotics and control of chronic GVHD, which is a risk factor of pneumococcal infection, seem to be important to prevent purulent genual arthritis.

Adolescent↗

Conservative treatment of Garden stage I femoral neck fracture in elderly patients.

We reviewed 38 patients aged 65 years and older with fresh Garden stage I femoral neck fractures treated nonsurgically to determine factors that influence fracture union. The mean follow-up period was 20 (range 6-86) months. Twenty-three (61%) fractures united within 6 months after injury, while 15 (39%) failed to unite. The percentage of united fractures was considerably higher (p < 0.01) in patients who began bed-to-wheelchair transfer training 14 days or later after injury than in those who began training within 13 days. The incidence of union was considerably higher (p < 0.05) in patients who began ambulation 20 days or later after injury than in those who began within 19 days. There was no statistical difference in the amount of valgus or retroversion of the femoral head between patients whose fractures united and those whose fractures did not. Patients without severe dementia regained the ability to walk significantly more frequently than did patients with severe dementia (p < 0.05).

Aged↗

Interaction between hydroxyapatite and proteins by liquid chromatography using simulated body fluids as eluents.

Hydroxyapatite (HAp) column chromatography for proteins using simulated body fluids (SBFs) as eluents was investigated in order to mimic the flow environment of human body fluid on the HAp surface in vivo. Acidic plasma proteins such as albumin, gamma-globulin, and fibrinogen having carboxyl groups with a negative charge were suggested to adsorb at positively charged sites (Ca sites) on the HAp surface. These acidic plasma proteins were not even eluted at higher inorganic ion molarities of human body fluid. Whereas basic proteins such as papin, cytochrome c, and lysozyme were easily eluted at lower inorganic ion molarities of human body fluid due to existing Na(+), Ca(2 +), Mg(2 +) and (CH(2)OH)(3)CNH(4)(+) ions in the eluents. The elution behavior of proteins using SBF in the presence or absence of glucose did not change. From these considerations, bone matrix proteins as acidic and neutral proteins would be considered an advantageous condition in order to adsorb on HAp in vivo.

Journal Article↗

The cross-linkage effect of hydroxyapatite/collagen nanocomposites on a self-organization phenomenon.

Hydroxyapatite(HAp)/collagen nanocomposites were prepared by a coprecipitation method controlling the degree of cross-linkage between collagen molecules using glutaraldehyde. The precipitates filtered were dried in a freeze drier or naturally dried in the air at 25 degrees C. The naturally dried cakes had open channels of 5-15 microm in diameters, which were three-dimensionally and regularly developed over the whole samples, and showed a pretty good mechanical strength. The channels that were formed at spaces among the HAp/collagen particles, cross-linked one another, which had been filled up with water before its evaporation. The ordering state of the open channels depended on the degree of cross-linkage with glutaraldehyde; the optimal self-organized state was found when 30 molecules of glutaraldehyde were added per collagen molecule, though an excess amount of glutaraldehyde suppressed the appearance of the ordered state. From SEM and FT-IR measurements, it was indicated that the self-organization in the HAp/collagen nanocompsites continuously occurred during the drying process together with the removal of water and the increase of the density.

Journal Article↗

Successful liquid storage of peripheral blood stem cells at subzero non-freezing temperature.

Although non-frozen storage of peripheral blood stem cells (PBSC) has been extensively studied and utilized clinically, the optimal storage conditions have not been determined. In order to improve the maintenance of clonogenic capacity during storage, we evaluated the feasibility of subzero non-freezing preservation of PBSC and attempted to determine the optimal conditions. Human PBSC were stored in different non-cryopreserved conditions. University of Wisconsin (UW) solution was used as the storage medium for PBSC. The stem cell integrity was optimally maintained when PBSC were preserved in a supercooled state at -2 degrees C in UW solution without any cryoprotectants, and the highest values for nucleated cell survival (91.6%), CFU-GM survival (67.3%) and trypan blue viability (92%) were achieved at 72 h. CFU-GM survival in our storage conditions was significantly better than the survival achieved with hypothermic preservation in autologous serum and ACD-A solution at 4 degrees C (67.3 +/- 9.2% vs 42.9 +/- 15.3%; P < 0.01) or cryopreservation at -80 degrees C (67.3 +/- 9.2% vs 52.7 +/- 10.7%; P < 0.01). Thus, the combination of supercooling and UW solution was the optimal non-freezing method of preserving transplantable PBSC tested here. This method is of clinical utility in peripheral blood stem cell transplantation (PBSCT) for its simplicity and storage efficiency, and has value as a short-term storage method for PBSC to support dose-intensive multicyclic chemotherapy.

Blood Cells↗

Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease.

BACKGROUND: The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome. AIMS: To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H. pylori eradication therapy. PATIENTS AND METHODS: Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years. RESULTS: Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred. CONCLUSION: Eradication of H. pylori infection changes the natural course of peptic ulcer.

Anti-Bacterial Agents↗

Analysis of mixed chimerism in patients after allogeneic stem cell transplantation using a capillary electrophoresis system.

We analyzed mixed chimerism (MC) after allogeneic stem cell transplantation (SCT) using a capillary electrophoresis system with four kinds of fluorescence-labeled primers for microsatellites (D3S1359, D6S89, ACTBP2, HGH). The sensitivities of all microsatellites were at least 3%. The present method is sufficiently rapid: only 3-4 h are needed to perform all the procedures. For analysis of MC in 30 patients who had undergone allogeneic SCT, heterozygosity of all microsatellites was over 88% and informativeness of ACTBP2 and HGH was over 73%. We analyzed MC using this technique to determine whether it was useful for prediction of the prognosis of 22 patients who had undergone allogeneic SCT. MC was more frequently observed in patients who were treated without total body irradiation (TBI) than in patients who were treated with TBI (p = 0.009). MC was also seen in a larger percentage of patients without acute graft-versus-host disease (p = 0.027). Six patients developed graft failure or relapse among 12 patients with MC. The graft failure or relapse was higher in patients with MC than in patients with complete chimerism (CC) (p = 0.009) especially if they were over 30 years of age (p = 0.0005). In contrast, graft failure or relapse was not higher in patients with MC compared with patients with CC under 30 years of age (p = 0.78). These results show that MC is an important predictive factor, especially in patients over 30 years of age.

Adolescent↗

Swelling behavior of hyaluronic acid and type II collagen hydrogels prepared by using conventional crosslinking and subsequent additional polymer interactions.

Polymer-polymer interactions, such as hydrophobic and electrostatic interactions, were introduced into covalently crosslinked composite matrices consisting of an anionic polysaccharide, hyaluronic acid (HyA) and a cationic polypeptide, type II collagen. The matrices were covalently crosslinked using a water soluble carbodiimide (WSC; 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride) and were immersed at different temperatures in excess water or 0.4 M NaCl aqueous solution, i.e. the optimal salt concentration to suppress polyion complex formation. Hydrophobic interaction was introduced in the matrices when the temperature was increased. Matrices with polymer-polymer interactions could be obtained when immersed in water at 37 degrees C without any collagen denaturation. The molar ratios of [OH]/[COOH] and [NH2]/[COOH], and WSC concentration in precursor solutions of HyA-collagen composite matrices influenced the electrostatic interactions. The hydrophobic and electrostatic interactions in the matrix were maintained in water, even at low temperatures, while in salt solutions at elevated temperatures, these interactions were nullified.

Biocompatible Materials↗

The cooperative action of angiotensin II with subluteolytic administration of PGF2alpha in inducing luteolysis and oestrus in the cow.

There is evidence that the potent vasoconstrictor angiotensin II (Ang II) regulates luteal functions. In the present study, the effect of an intraluteal injection of Ang II alone or in combination with pretreatment with a subluteolytic i.m. dose of PGF(2alpha) on the concentration of plasma progesterone, corpus luteum regression and duration of the oestrous cycle was investigated. Cows were assigned randomly to receive an intraluteal injection of either: (i) 500 microl saline 30 min after i.m. administration of saline (control, n = 7); (ii) 500 microl saline 30 min after i.m. administration of a subluteolytic dose (125 microg) of a PGF(2alpha) analogue (1/4 PGF(2alpha), n = 5); (iii) 2 mg Ang II in 500 microl saline 30 min after i.m. administration of saline (Ang II, n = 5); or (iv) 2 mg Ang II in 500 microl saline 30 min after i.m. administration of a subluteolytic dose (125 microg) of the PGF(2alpha) analogue (1/4 PGF(2alpha)/Ang II, n = 6) on day 12 of the oestrous cycle. There were no significant changes in plasma progesterone concentrations in the control, 1/4 PGF(2alpha) or Ang II treatment groups. Treatment with 1/4 PGF(2alpha)/Ang II decreased plasma progesterone concentration, and induced luteolysis and oestrus. The onset of oestrus in cows treated with full-dose (500 microg) PGF(2alpha) (3.1 +/- 0.2 (mean +/- SEM) days after treatment) was significantly earlier than that in cows treated with 1/4 PGF(2alpha)/Ang II (4.8 +/- 0.2 days after treatment) (P < 0.05). The results from the present study demonstrate that an intraluteal injection of Ang II after i.m. administration of a subluteolytic dose of PGF(2alpha) analogue induces luteolysis and oestrus. Thus, these results support the contention that Ang II is directly correlated with the process of luteal regression in cows.

Angiotensin II↗

Involvement of tetrahydrobiopterin in trophic effect of erythropoietin on PC12 cells.

Tetrahydrobiopterin (BH(4)) synthesis is reported to be stimulated by nerve growth factor (NGF) in PC12 cells, suggesting involvement of BH(4) in the trophic effect of NGF. We have recently reported that erythropoietin (EPO) and BH(4) enhance survival of PC12 cells. In the present study, we investigated involvement of BH(4) in the trophic effect of EPO on PC12 cells. Cellular BH(4) content was increased by EPO (10(-10) to 10(-8) M) in a dose- and time-related manner. EPO (10(-10) to 10(-8) M) increased the viable cell number of PC12 cells. In addition to EPO, BH(4) (1, 3, and 10 microM) increased the viable cell number of PC12 cells. Administration of 0.3 mM 2,4-diamino-6-hydroxypyrimidine, an inhibitor of BH(4) synthesis, blunted EPO-induced increases in BH(4) content and the viable cell number of PC12 cells. These results taken together suggest that BH(4) is involved in the trophic effects of EPO on PC12 cells.

Animals↗

CD40 ligand promotes priming of fully potent antitumor CD4(+) T cells in draining lymph nodes in the presence of apoptotic tumor cells.

The presence or absence of CD4(+) T cell help can determine the direction of adaptive immune responses toward either cross-priming or cross-tolerance. It has been demonstrated that interactions of CD40-CD40 ligand can replace CD4(+) T cell help and enable dendritic cells to prime cytotoxic T cells. Here, we demonstrate that antitumor reactivity induced in regional lymph nodes (LNs) by s.c. injection of CD40 ligand (CD40L)-transduced tumor (MCA205 CD40L) showed far superior therapeutic efficacy against established brain tumors of a weakly immunogenic fibrosarcoma, MCA205, when adoptively transferred. Coinjection of apoptotic, but not necrotic parental tumor cells with CD40L-expressing tumor cells caused a strong synergistic induction of antitumor reactivity in tumor-draining LNs. Freshly isolated T cells from LNs immunized with apoptotic parental tumor cells and MCA205 CD40L were capable of mediating regression of the parental tumor in vivo. In contrast, T cells derived from LNs immunized without MCA205 CD40L required ex vivo anti-CD3/IL-2 activation to elicit therapeutic activity. On anti-CD3/IL-2 activation, cells from LNs immunized with MCA205 CD40L exhibited superior per cell antitumor reactivity. An in vitro depletion study revealed that either CD4(+) or CD8(+) T cells could mediate therapeutic efficacy but that the antitumor efficacy mediated by CD4(+) T cells was far superior. Cytosolic flow cytometric analyses indicated that priming of CD4(+) cells in LNs draining CD40L-expressing tumors was polarized to the Th1 type. This is the first report that fully potent antitumor CD4(+) T cell priming was promoted by s.c. injection of CD40L-transduced tumor in the presence of apoptotic tumor cells.

Animals↗

Heterogeneous expression of Toll-like receptor 4 and downregulation of Toll-like receptor 4 expression on human gingival fibroblasts by Porphyromonas gingivalis lipopolysaccharide.

Porphyromonas gingivalis (P. gingivalis) is implicated in the initiation and progression of periodontitis. Human gingival fibroblasts (HGFs) are the major constituent of gingival connective tissue. P. gingivalis or its components such as lipopolysaccharide (LPS) upregulate the production of various inflammatory cytokines including interleukin (IL)-1 and IL-6 in HGFs. Recently, we demonstrated that the binding of P. gingivalis LPS to Toll-like receptor 4 (TLR4) on HGFs activates various second messenger systems (Biochem. Biophys. Res. Commun. 273, 1161-1167, 2000). In the present study, we examined the level of TLR4 expression on HGFs by flow cytometric analysis (FACS), and studied the levels of IL-1 and IL-6 in the culture medium upon LPS stimulation of HGFs by enzyme-linked immunosorbent assay (ELISA). Upon stimulation by P. gingivalis LPS for 24 h, HGFs that expressed a high level of TLR4 secreted significantly higher levels of IL-1 and IL-6 than HGFs that expressed a low level of TLR4. On the other hand, after stimulation with P. gingivalis LPS for 24 h, the level of TLR4 on the surface of HGFs decreased. These results suggest that the level of TLR4 expression on HGFs reflects the extent of inflammation in the gingival tissue, and that P. gingivalis LPS downregulates TLR4 expression on HGFs. These findings may be used to control inflammatory and immune responses in periodontal disease.

Antibodies, Monoclonal↗

Combinatorial evaluation of the chiral discrimination of permethylated carbohydrates using fast-atom bombardment mass spectrometry.

The chiral discrimination abilities of several variously permethylated carbohydrates toward various amino acid 2-propyl esters were combinatorially evaluated from the relative peak intensity of the 1:1 diastereomeric complex ions with the deuterium-labeled L-amino acid 2-propyl ester protonated ion and with the unlabeled D-amino acid 2-propyl ester protonated ions in FAB mass spectrometry. The chiral discrimination abilities evaluated using FAB mass spectrometry approximately corresponded to the ratio of the association constants (K(R)/K(S)) toward each enantiomer in the solution. Therefore, this evaluation method is very useful for the screening of the chiral discrimination abilities of carbohydrates and their derivatives.

Amino Acids↗

Expressions of neuropilin-1, neuropilin-2 and semaphorin 3A mRNA in the rat brain after middle cerebral artery occlusion.

This study investigated the spatial and temporal expressions of mRNA encoding neuropilin (Npn)-1, Npn-2 and semaphorin3A (Sema3A) in the rat brain after occlusion of the middle cerebral artery (MAC) distal to the striate branches. The expression of Npn-1 mRNA was transiently upregulated in layers V and VI of the parietal cortex not entering infarction on the lesion side from 3 to 6 h after MCA occlusion. The transient up-regulation of Npn-1 mRNA expression was presumably accompanied by an increase in Npn-1 protein as shown by immunohistochemistry in combination with in situ hybridization histochemistry. Intense Npn-2 mRNA expression was noted temporarily in layer II of the parietal cortex on the lesion side from 1 to 6 h after MCA occlusion. The expression of Sema3A mRNA was upregulated in layer VI of the non-infarcted parietal cortex on the lesion side at 6 h after MCA occlusion. The above increases in mRNA expression were no longer observed at 12 h after MCA occlusion. The expressions of Npn-1, -2 and Sema3A mRNA were not detected in the ventroposterior thalamic nucleus undergoing secondary degeneration after MCA occlusion. In the infarct lesion or ischemic core, neuronal expressions of Npn-1, -2 and Sema3A disappeared by 3 days after MCA occlusion as the neurons in situ entered apoptosis or necrosis. In contrast, ED-1-positive microglia/macrophages with Npn-1 and Npn-2 mRNA were observed in the infarct lesion at 1 week after MCA occlusion. These findings suggest that the temporal up-regulation of Npn-1 and Sema 3A mRNA expressions in the non-infarcted parietal cortex on the lesion side is insufficient to induce neuronal cell death possibly because the up-regulated mRNA molecules are not fully translated and that the overexpression of Npn-1 and/or Npn-2 in the ischemic core with degenerating neurons enables activated microglial cells to contact the damaged neurons in situ for phagocytosis.

Animals↗

Increased expression of the sterol regulatory element-binding protein-1 gene in insulin receptor substrate-2(-/-) mouse liver.

Insulin receptor substrate (IRS)-2(-/-) mice develop diabetes because of insulin resistance in the liver and failure to undergo beta-cell hyperplasia. Here we show by DNA chip microarray analysis that expression of the sterol regulatory element-binding protein (SREBP)-1 gene, a downstream target of insulin, was paradoxically increased in 16-week-old IRS-2(-/-) mouse liver, where insulin-mediated intracellular signaling events were substantially attenuated. The expression of SREBP-1 downstream genes, such as the spot 14, ATP citrate-lyase, and fatty acid synthase genes, was also increased. Increased liver triglyceride content in IRS-2(-/-) mice assures the physiological importance of SREBP-1 gene induction. IRS-2(-/-) mice showed leptin resistance; low dose leptin administration, enough to reduce food intake and body weight in wild-type mice, failed to do so in IRS-2(-/-) mice. Interestingly, high dose leptin administration reduced SREBP-1 expression in IRS-2(-/-) mouse liver. Thus, IRS-2 gene disruption results in leptin resistance, causing an SREBP-1 gene induction, obesity, fatty liver, and diabetes.

ATP Citrate (pro-S)-Lyase↗