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Biomedical subjects

K Tanabe

Publications and source records attributed to K Tanabe.

At least 73 records · Page 4Linked to original sources
PubMed2001

The role of intracellular Ca(2+) in apoptosis induced by hyperthermia and its enhancement by verapamil in U937 cells.

PURPOSE: The relationship between apoptosis induced by 42 degrees C and 44 degrees C hyperthermia alone or in combination with verapamil and changes in intracellular Ca(2+) concentration ([Ca(2+)]i) was investigated in U937 cells. METHODS: Apoptosis induced by hyperthermia was assessed according to DNA fragmentation, nuclear morphologic changes, and expression of phosphatidylserine on the outside plasma cell membrane. These changes were measured by flow cytometry. The [Ca(2+)]i of individual cells after hyperthermia was monitored by a digital image-analyzing technique using Fura-2. RESULTS: Hyperthermia-induced apoptosis reached a plateau after 6 h and was found to be both time and temperature-dependent. DNA fragmentation was maximum at 44 degrees C after 30 min. Verapamil enhanced the apoptosis induced by 42 degrees C and 44 degrees C hyperthermia in normal cells and by 44 degrees C hyperthermia in thermotolerant cells. The number of cells containing higher [Ca(2+)]i (more than 200 nM) was significantly increased by hyperthermia and further elevated by the addition of verapamil in both normal and thermotolerant cells. Apoptosis induced by hyperthermia was markedly decreased by an intracellular Ca(2+) chelator, BAPTA-AM, in a dose-dependent manner. CONCLUSION: These results indicate that [Ca(2+)]i increase plays a crucial role in apoptosis induced by hyperthermia and the combined treatment with verapamil in normal and thermotolerant U937 cells. Furthermore, hyperthermia-combined drug therapy has potential significance in cancer therapy.

Apoptosis↗
PubMed2001

Synthesis and properties of peptide nucleic acids containing a psoralen unit.

We prepared the psoralen PNA unit from 8-methoxypsoralen and synthesized various PNAs containing psoralen by a typical (t)()Boc method. PNAs containing psoralen (P-PNA) at strand end formed a stable duplex with complementary DNA. The hybridization of P-PNA with complementary DNA resulted in a considerable decrease of the psoralen fluorescence.

Base Sequence↗
PubMed2001

Effect of pre-and postoperative plasmapheresis on posttransplant recurrence of focal segmental glomerulosclerosis in children.

BACKGROUND: Posttransplant recurrence is frequent in patients who received renal transplantation for focal segmental glomerulosclerosis (FSGS). The recurrence has been ascribed to a circulating permeability factor or factors. We have used plasmapheresis (PP) to treat recurrent FSGS and also studied whether preoperative PP is effective in preventing recurrence of FSGS. METHODS: We retrospectively analyzed 21 allografts of 20 patients with nephrotic syndrome and biopsyproven FSGS. They were divided into two groups depending on whether they had prophylactic PP; a prophylactic (n=15) and a nonprophylactic group (n=6). PP was performed two to three times prophylactically and therapeutically until proteinuria was markedly reduced. In each session, 50-75 ml/kg of the patient's plasma was exchanged with 5-8% albumin. RESULTS: FSGS recurred in 9 of 21 allografts, 4 of 6 in the nonprophylactic group, and 5 of 15 in the prophylactic group. Therapeutic PP was performed in seven of nine recurrent patients without definite adverse effect, with satisfactory results except in one patient. Children lost proteinuria after 6 to > 100 sessions of PP and the number correlated with the pretreatment level of proteinuria. The mean follow-up periods were 62.7 and 41.6 months for the prophylactic and nonprophylactic groups, respectively. At the last follow-up, 66.7% of relapsing and 81.8% of nonrelapsing patients had a functioning graft. CONCLUSION: PP appears to be effective for the prevention and treatment of posttransplant recurrence of FSGS, although further consideration of cost/benefit and risks is required before a conclusive judgement can be made.

Child↗
PubMed2001

LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phosphorylation at threonine-505.

LIM-kinase 1 and 2 (LIMK1 and LIMK2) phosphorylate cofilin and induce actin cytoskeletal reorganization. LIMK1 is activated by Rho-associated, coiled-coil-forming protein kinase (ROCK) and p21-activated kinase 1 (PAK1), but activation mechanisms and cellular functions of LIMK2 have remained to be determined. We report here that LIMK1 and LIMK2 phosphorylate both cofilin and actin-depolymerizing factor (ADF) specifically at Ser-3 and exhibit partially distinct substrate specificity when tested using site-directed cofilin mutants as substrates. We also show that LIMK2 is activated by ROCK by phosphorylation at Thr-505 within the activation loop. Wild-type LIMK2, but not its mutant (T505V) with replacement of Thr-505 by Val, was activated by ROCK in vitro and in vivo. LIMK2 mutants with replacement of Thr-505 by one or two Glu residues (T505E or T505EE) increased the kinase activity about 3.6-fold but were not further activated by ROCK. When expressed in HeLa cells, wild-type LIMK2, but not the T505V mutant, induced the formation of stress fibres, focal adhesions and membrane blebs. Furthermore, inhibitors of Rho and ROCK significantly suppressed LIMK2-induced stress fibres and membrane blebs. These results suggest that LIMK2 functions downstream of the Rho-ROCK signalling pathway and plays a role in reorganization of actin filaments and membrane structures, by phosphorylating cofilin/ADF proteins.

Actin Depolymerizing Factors↗
PubMed2001

Involvement of p38 MAP kinase in TGF-beta-stimulated VEGF synthesis in aortic smooth muscle cells.

Although it is known that transforming growth factor (TGF)-beta induces vascular endothelial growth factor (VEGF) synthesis in vascular smooth muscle cells, the underlying mechanisms are still poorly understood. In the present study, we examined whether the mitogen-activated protein (MAP) kinase superfamily is involved in TGF-beta-stimulated VEGF synthesis in aortic smooth muscle A10 cells. TGF-beta stimulated the phosphorylation of p42/p44 MAP kinase and p38 MAP kinase, but not that of SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase). The VEGF synthesis induced by TGF-beta was not affected by PD98059 or U0126, specific inhibitors of the upstream kinase that activates p42/p44 MAP kinase. We confirmed that PD98059 or U0126 did actually suppress the phosphorylation of p42/p44 MAP kinase by TGF-beta in our preparations. PD169316 and SB203580, specific inhibitors of p38 MAP kinase, significantly reduced the TGF-beta-stimulated synthesis of VEGF (each in a dose-dependent manner). PD169316 or SB203580 attenuated the TGF-beta-induced phosphorylation of p38 MAP kinase. These results strongly suggest that p38 MAP kinase plays a part in the pathway by which TGF-beta stimulates the synthesis of VEGF in aortic smooth muscle cells.

Animals↗
PubMed2001

Contrasting effects of midazolam on induction of heat shock protein 27 by vasopressin and heat in aortic smooth muscle cells.

We previously showed that vasopressin stimulates the induction of heat shock protein (HSP) 27, a low molecular-weight HSP, through protein kinase C activation in aortic smooth muscle A10 cells. In the present study, we examined the effects of midazolam, an intravenous anesthetic, on the HSP27 induction stimulated by vasopressin, heat, or sodium arsenite (arsenite) in A10 cells. Midazolam inhibited the accumulation of HSP27 induced by vasopressin or 12-O-tetradecanoylphorbol 13-acetate (TPA), a direct activator of protein kinase C. Midazolam also reduced the vasopressin-induced level of the mRNA for HSP27. In contrast, midazolam enhanced the HSP27-accumulation induced by heat or arsenite. Midazolam also enhanced the heat-increased level of the mRNA for HSP27. However, midazolam had no effect on the dissociation of the aggregated form of HSP27 following stimulation by vasopressin, heat, or arsenite. These results suggest that midazolam suppresses vasopressin-stimulated HSP27 induction in vascular smooth muscle cells, and that this inhibitory effect is exerted at a point downstream from protein kinase C. In contrast, midazolam enhanced heat- or arsenite-stimulated HSP27 induction. Thus, midazolam has dual effects on the HSP27 induction stimulated by various stresses in vascular smooth muscle cells.

Anesthetics, Intravenous↗
PubMed2001

A major determinant quantitative-trait locus responsible for atopic dermatitis-like skin lesions in NC/Nga mice is located on Chromosome 9.

NC/Nga (NC) is a newly discovered model mouse for human atopic dermatitis, NC mice showing specific symptoms such as dermatitis and overproduction of IgE. To detect the loci responsible for the onset of dermatitis in the mice, backcross (N2) progeny between (NCxMSM/MS)F1 and NC were generated, where MSM/MS is an inbred strain from Japanese wild mice, Mus musculus molossinus. Linkage disequilibrium between dermatitis and various chromosome-specific microsatellite markers was then examined in the N2 segregants with severe dermatitis. The analysis revealed that the locus of the major determinant (designated here as derm1) was tightly linked to D9Mit163, D9Mit72, D9Mit143, D9Mit103, D9Mit207, and D9Mit209, because these markers showed the highest and most significant chi2 values. Since no recombination was observed among the markers in our linkage map, a radiation hybrid (RH) panel was applied to locate the derm1 locus more precisely. The markers were separated on the RH map, and their order was D9Mit163-D9Mit72-D9Mit143-D9Mit103-D9Mit207-D9Mit209 from the centromere. Several functional candidate genes are located near the locus derm1. These candidates are Thy1, Cd3d, Cd3e, Cd3g, Il10ra, 1118, and Csk, all of which could be involved in allergic responses through effects on T-cell function. Of these candidates, Csk is the strongest for NC dermatitis, since its map position was most tightly linked to the derm1 locus.

Animals↗
PubMed2001

Long-term outcome of ABO-incompatible renal transplantation.

Based on the long-term experience with ABO-incompatible kidney transplantation, the following can be concluded: 1. Renal transplantation across ABO incompatibility is an acceptable treatment for patients with end-stage renal failure. [table: see text] 2. Long-term patient and graft survival in ABO-incompatible kidney transplantation is influenced primarily by acute rejection episodes occurring within 1 year. 3. Despite the removal of anti-ABO natural antibodies before transplantation, hyperacute rejection crises may occur in some cases. 4. Humoral rejection is the most prominent type of rejection in ABO-incompatible renal transplantation. Even though most of this rejection is controllable with anti-rejection therapy, the prognosis for a graft that undergoes humoral rejection is significantly poor. 5. The maximum IgG titers of anti-A/B antibody before transplantation may have a harmful effect on graft acceptance in ABO-incompatible kidney transplantation. 6. Renal transplantation across ABO incompatibility is principally the most significant risk factor to affect long-term allograft function in ABO-incompatible living kidney transplantation.

ABO Blood-Group System↗
PubMed2001

Design of an SHD-distributed database over IP to support telemedicine.

We have conducted tests utilizing superhigh-definition CRTs (hereafter, referred to as a "super high-definition image system," or "SHD ": 2,048 x 2,048 pixels, 24-bit RGB gradation, noninterlace system) for autonomous and distributed medical image database systems. The system is capable of providing six times the image definition of a hi-vision television (HDTV). The aim in designing and testing the system is to enable gigabit network connectivity while displaying images on a DOS- V machine. This paper discusses how we devised an integrated environment for managing and operating distributed an SHD image database to support Telemedicine linking with ATM, with INS-1500, and with dial-up IP connection.

Computer Communication Networks↗
PubMed2001

A case of rapid progressive glomerulonephritis with IgA deposits after renal transplantation.

A 46-yr-old Japanese male who underwent a second cadaveric kidney transplantation on 31 October 1996 after suffering Type II diabetic mellitus for 25 yr was admitted to our institute on 23 January 1999, because of colicky abdominal pain and abdominal discomfort. Elevated levels of serum creatinine, severe proteinuria and microscopic haematuria were observed. The allograft biopsy specimen disclosed crescentic glomerulonephritis. Immunofluorescence showed granular deposits of mainly IgA and C3 along glomerular capillary walls and mesangial areas. Electron microscopy showed extensive subepithelial and mesangial electron dense deposits. Rapid and irreversible worsening of graft function led to resumption of haemodialysis on 31 May 1999. We speculated that this case was an atypical form of de novo Henoch-Schönlein purpura nephritis (HSPN) in transplanted kidney because of the histopathological findings of the allograft biopsy and clinical symptoms.

Cadaver↗
PubMed2001

Clinical and pathological assessment of acute vascular rejection in the transplant kidney.

Acute vascular rejection (AVR) in kidney transplantation is the most important factor influencing graft prognosis. We focus on patients whose grafts were lost because of AVR, and assessed their clinical characteristics and histological findings of biopsied renal grafts. Biopsied specimens exhibited AVR in 43 patients who underwent kidney transplantation in the Kidney Center of Tokyo Women's Medical University from 1995 to 1999. In the follow-up from 1 to 5 yr (median: 2.5 yr) we classified these patients into three groups: favourable prognosis group (FPG), relatively poor prognosis group (RPPG) and poor prognosis group (PPG). Light microscopic study for histological grading of acute rejection according to the Banff scheme and detection of the C4d complement deposition on peritubular capillaries by the immunofluorescence method were performed. Based on the results, the donors of RPPG and PPG were significantly older than those of FPG, and all factors of acute rejection according to the Banff scheme were not statistically significantly different among the three groups. However, an acute tubular injury mimicking acute tubular necrosis (ATN) was observed in the biopsy specimens from PPG. In conclusion, an older donor is a risk factor of poor prognosis of the graft with AVR, and acute tubular injury mimicking ATN is one of the important features that enables the prediction of graft failure originating from AVR in kidney transplantation.

Acute Disease↗
PubMed2001

Inherited factor H dysfunction and complement-associated glomerulonephritis in renal grafts of first and second transplantations.

A 38-yr-old man with factor H dysfunction and unknown glomerular disease received first and second renal transplantations (Tx) from living-related donors. His examination showed a low percentage activity of factor H (31%). Factor H dysfunction has been known to be associated with type II or III membranoproliferative glomerulonephritis (MPGN), haemolytic uraemic syndrome and IgA GN. The first graft from his mother showed diffuse mesangial deposit of IgA. His son has had IgA GN and his data also revealed a low percentage activity of factor H (33%). He and his son both showed a low activity of C3. Moreover, his father, who was the donor of the second Tx, had a low percentage activity of factor H (25%), and presented with mild glomerular deposit of C3 at operation, while he has been healthy through his entire 67 yr of life. Each of them had a low percentage activity of factor H. These findings through three generations suggested the inheritance of factor H dysfunction. The patient presented with proteinuria 3 months after the first Tx. At the first biopsy 30 months after the first Tx, light microscopy revealed minor glomerular abnormalities with electron dense deposits in subepithelial, intramembranous and mesangial regions, while immunofluorescence showed massive glomerular deposits of C3. In the second biopsy 51 months after the first Tx, the glomerulonephritis developed mesangial proliferation and crescent formation, accompanied by more massive C3 deposit and intramembranous, mesangial and subepithelial dense deposits. He then required redialysis. At the second and third biopsies within 2 months after the second Tx, the renal graft showed similar findings to the first biopsy after the first Tx. He perhaps presented with a recurrence of complement-associated GN, showing an atypical form of MPGN after Tx. These findings suggest that factor H dysfunction may play an important role of a certain pathogenesis of GN.

Adult↗
PubMed2001

Periodontal ligament cells secrete the factor that inhibits osteoclastic differentiation and function: the factor is osteoprotegerin/osteoclastogenesis inhibitory factor.

The periodontal ligament, a highly specialized connective tissue situated between the tooth and the alveolar bone of the tooth socket, has been thought to influence the remodeling of the alveolar bone. The effects of two human periodontal ligament fibroblastic cell populations (HPLFs) on osteoclast-like cell (OCL) formation and the function of authentic osteoclasts were examined. The addition of the conditioned media (CM) from both HPLF cultures (HPLF-CMs) to mouse bone marrow culture inhibited OCL formation in spite of the presence of 10(-8)M 1alpha, 25 dihydroxyvitamin D3 (1alpha,25(OH)2D3). This inhibitory effect was most remarkable when both CMs were added during day 6 to day 9 following bone marrow culture, just at the late stage of OCL differentiation. HPLF-CMs also induced a significant decrease in the pit area and the pit number formed by authentic osteoclasts on ivory slices. The administration of neutralizing monoclonal antibody (OI-1) against human osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) with HPLF-CMs to mouse bone marrow culture almost completely blocked the inhibitory effect of these CMs on OCL formation. Immunofluorescent examination of HPLF with OI-1 revealed intense positive reactivity in the cytoplasm. Western blot analysis of HPLF-CM using anti-human OPG/OCIF polyclonal antibody resulted in the detection of bands of 60 kDa and 120 kDa which were consistent with those of OPG/OCIF. These results suggest that HPLF cells produce and secrete OPG/OCIF, and that this factor from HPLF prevents the differentiation of the late preosteoclast and the function of the mature osteoclasts.

Adolescent↗
PubMed2001

Differences in survival-promoting effects and intracellular signaling properties of BDNF and IGF-1 in cultured cerebral cortical neurons.

Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) act on various neurons of the CNS as neurotrophic factors promoting neuronal differentiation and survival. We examined the survival-promoting effects of BDNF and IGF-1 on serum deprivation-induced death in cultured cerebral cortical neurons, and compared the intracellular signaling pathways stimulated by BDNF and IGF-1 in the neurons. We found that the survival-promoting effect of BDNF was much weaker than that of IGF-1 in serum deprivation-induced death of cultured cortical neurons. We found no differences in the levels of phosphatidylinositol 3-kinase (PtdIns3-K) activity or Akt (also called PKB) phosphorylation induced by BDNF and IGF-1 in the cultured cortical neurons, although many reports suggest that PtdIns3-K and Akt are involved in survival promotion. In addition, phosphorylation signals of mitogen-activated protein kinase (MAPK) and cAMP responsive element-binding protein (CREB), which have also been reported to be involved in survival promotion, were stimulated by BDNF much more potently than by IGF-1. These results show that there may be, as yet unidentified, intracellular signaling pathways other than the PtdIns3-K-Akt, MAPK and CREB signaling, to regulate survival promotion. These unidentified signaling pathways may be responsible for the distinct strengths of the survival-promoting effects of BDNF and IGF-1.

Animals↗
PubMed2001

Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation.

BACKGROUND: Cilostazol is an antiplatelet agent that increases the intracellular concentration of cyclic adenosine monophosphate by inhibiting phosphodiesterase III; it has been shown to reduce neointimal hyperplasia in animal balloon injury models. METHODS: One hundred thirty patients who underwent elective stenting (Palmaz-Schatz stent) were randomly assigned to cilostazol treatment 200 mg/d (n = 65) or to ticlopidine treatment 200 mg/d (n = 65). Angiographic follow-up was performed at 6 months, and clinical follow-up was continued up to 1 year. RESULTS: One sudden death and one myocardial infarction resulting from subacute occlusion were observed in the ticlopidine group. Drug adverse effects were observed in 3 patients in the cilostazol group, as opposed to 6 patients in the ticlopidine group. In the intention-to-treat analysis, 56 patients (61 lesions) in the cilostazol group and 58 patients (58 lesions) in the ticlopidine group were assessed with quantitative coronary angiography. Late loss in the cilostazol group was smaller (0.58+/-0.52 mm vs. 1.09+/-0.65 mm, P<.0001) than in the ticlopidine group. The restenosis rate was lower in the cilostazol group than in the ticlopidine group (16% vs. 33%, P = .044). The target vessel revascularization rate at 1 year was 23% in the cilostazol group and 42% in the ticlopidine group (P =.03). CONCLUSIONS: The results of this study suggest that cilostazol may be a safe medication that is effective in preventing restenosis after stent implantation.

Cilostazol↗
PubMed2001

Enhancement of hyperthermia-induced apoptosis by a free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride, in human histiocytic lymphoma U937 cells.

To elucidate the mechanism how a free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), induces cell death at hyperthermic temperatures, apoptosis in a human histiocytic lymphoma cell line, U937, was investigated. Free radical formation deriving from the thermal decomposition of AAPH was examined by spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). An assay for DNA fragmentation, observation of nuclear morphological changes, and flow cytometry for phosphatidylserine (PS) externalization were used to detect apoptosis and revealed enhancement of 44.0 degrees C hyperthermia-induced apoptosis by free radicals due to AAPH. However, free radicals alone derived from AAPH did not induce apoptosis. Hyperthermia induced the production of lipid peroxidation (LPO), an increase in intracellular Ca2+ concentration ([Ca2+]i) and enhanced expression of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). The effects of hyperthermia on LPO and [Ca2+]i were enhanced markedly by the combination with AAPH. A significant decrease in Bcl-2 expression, increase in Bax expression, a loss of mitochondrial membrane potential (delta psi m) and a marked increase in cytochrome c expression were found only in cells treated with hyperthermia and AAPH. Although an intracellular Ca2+ ion chelator, BAPTA-AM, completely inhibited DNA fragmentation, water-soluble vitamin E, Trolox, only partially suppressed DNA fragmentation and the increase in [Ca2+]i. In contrast, LPO was inhibited completely by Trolox, but no inhibition by BAPTA-AM was found. These results suggest that apoptosis induced by hyperthermia alone is due to the increase in [Ca2+]i arising from increased expression of IP3R1 and LPO. Additional increase in [Ca2+]i due to increased LPO and the activation of mitochondria-caspase dependent pathway play a major role in the enhancement of apoptosis by the combination with hyperthermia and AAPH.

Amidines↗