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Biomedical subjects

Y Furukawa

Publications and source records attributed to Y Furukawa.

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

Novel mechanism of blocking axonal Na(+) channels by three macrocyclic polyamine analogues and two spider toxins.

1. The mechanism of Na(+) channel block by three macrocyclic polyamine derivatives and two spider toxins was studied with voltage clamp and internal perfusion method in squid axons. 2. All these chemicals specifically block Na(+) channels in the open state only from the internal surface, and do not affect K(+) channels. 3. The blocking effect is enhanced as the depolarizing pulse becomes larger. Blocked channels are unable to shift to the inactivated state. 4. In the case of cyclam and guanidyl-side armed cyclam (G-cyclam), quick release of these chemicals from the binding sites is proven by the increase in the tail current and prolongation of the time course of the off gating current. On the other hand, in the presence of N-4 and the spider toxins, their detachment was delayed significantly. 5. Molecular requirements for the block of Na(+) channels by these molecules are the presence of positive charge and hydrophobicity.

Algorithms↗
PubMed2001

Prognostic factors for survival and bladder recurrence in transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare. METHODS: The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier METHOD: Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis. RESULTS: The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis. CONCLUSIONS: The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.

Administration, Intravesical↗
PubMed2001

Vasoactive intestinal peptide regulates its receptor expression and functions of human keratinocytes via type I vasoactive intestinal peptide receptors.

Vasoactive intestinal peptide has been suggested to play some roles in inflammatory dermatoses such as atopic dermatitis and psoriasis. The aim of this study is to clarify the precise mechanisms of how vasoactive intestinal peptide is implicated in the pathogenesis of these disorders. We investigated the expression of vasoactive intestinal peptide and its receptors in normal human fibroblasts and keratinocytes, as well as in a human epidermal keratinocyte cell line DJM-1, using reverse transcription polymerase chain reaction and northern blotting. Type I VIP receptor mRNA was expressed in normal human keratinocytes and DJM-1 cells, and the latter also expressed type II receptor in lesser amounts. Neither type I nor type II VIP receptor mRNA was detected in fibroblasts, and vasoactive intestinal peptide transcript was not found in any cells examined. Type I VIP receptor mRNA was upregulated by Th1 cytokines (interferon-gamma), Th2 cytokines (interleukin-4), and tumor necrosis factor alpha, as well as vasoactive intestinal peptide itself, suggesting the presence of an autoregulatory loop. Vasoactive intestinal peptide increased cAMP production and cell proliferation of DJM-1 cells, and also induced the production of inflammatory cytokines such as interleukin-6, interleukin-8, and RANTES. The production of cAMP and cytokines was abrogated by a type I VIP receptor selective antagonist, indicating that type I receptor mediates these effects. Overall, these results suggest that upregulation of vasoactive intestinal peptide receptors by cytokines from inflammatory cells in the dermis enhances the proliferation and cytokine production of keratinocytes in response to vasoactive intestinal peptide from nerve endings. This cytokine network around keratinocytes may be involved in the pathogenesis of inflammatory dermatoses.

Cell Division↗
PubMed2001

Long-term zinc deficiency decreases taste sensitivity in rats.

The effects of zinc deficiency on taste sensitivity were examined in rats by recording the electrophysiological responses of the chorda tympani (CT) nerve and by use of a preference test. Male 4-wk-old Sprague-Dawley rats were given free access to a diet containing 2.2 (zinc-deficient), 4.1 (low zinc) or 33.7 (zinc-sufficient) mg zinc/kg diet. A fourth group was pair-fed the zinc-sufficient diet (with respect to the zinc-deficient rats). A two-bottle preference test using 0.15 mol/L NaCl and water revealed that NaCl preference was greater in the zinc-deficient and low zinc groups than in the control groups (zinc-sufficient and pair-fed) after 4 d of feeding. In the case of quinine hydrochloride solution (0.01 mmol/L), the preference was greater in zinc-deficient rats than in the other groups after 9 d, and the low zinc rats never showed a preference. Electrophysiological recording indicated that in the zinc-deficient rats, the CT nerve response to 0.20 mol/L NaCl was significantly less than that in the control rats after 21 d of feeding. In the low zinc rats, this response was significantly less than in the control rats after 35 d. The responses to quinine hydrochloride (0.02 mol/L), L-glutamic acid, HCl (0.01 mol/L) and NH(4)Cl (0.25 mol/L) in the zinc-deficient rats were not significantly reduced until d 42. These findings suggest that long-term zinc deficiency decreases taste sensitivity at the level of the CT nerve and that the change in NaCl preference due to zinc deficiency occurs before any change in NaCl taste sensitivity.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Surgical program for craniosynostosis using three-dimensional solid model, combined with autologous blood transfusion in a Japanese craniofacial unit.

Since April 1997 at St. Mary's Craniofacial Unit, simulated surgery using a three-dimensional solid model made preoperatively was carried out, which enable sufficient autologous blood banking before the surgery. This study was conducted in eight patients presenting with plagiocephaly, brachycephaly, and oxycephaly consisting of simple craniosynostosis and syndromic craniosynostosis. Four cases (numbers 1-4) conducted with simulated surgery using three-dimensional solid models and fronto-orbital advancement with reshaping, as well as autologous blood transfusion were selected for the later-term group. For the first-term group, four cases (numbers 5-8) that were performed before the introduction of the abovementioned treatment were selected. The later-term group compared with the first-term group showed a decrease in operating time by an average of 1 hour, blood loss during surgery by 90 ml, and one fifth the amount of homologous blood transfusion. Also, 2 cases in the later-term group (cases 3 and 4) were able to avoid homologous blood transfusion, and they had autologous blood transfusion of 30 to 33 ml/kg. The surgical techniques will be improved with repeated cases of simulated surgery, aiming for the minimum invasive surgery. Also, the use of autologous blood transfusion is expected to increase as a less invasive surgery.

Blood Loss, Surgical↗
PubMed2001

Effects of sugar on vegetative development and floral transition in Arabidopsis.

Although sugar has been suggested to promote floral transition in many plant species, growth on high concentrations (5% [w/v]) of sucrose (Suc) significantly delayed flowering time, causing an increase in the number of leaves at the time of flowering in Arabidopsis. The effect of high concentrations of Suc seemed to be metabolic rather than osmotic. The delay of floral transition was due to extension of the late vegetative phase, which resulted in a delayed activation of LFY expression. In addition, growth on low concentrations (1% [w/v]) of Suc slightly inhibited flowering in wild-type plants. This delay resulted from effects on the early vegetative phase. This inhibition was more pronounced in tfl1, an early flowering mutant, than in the wild type. Although 1% (w/v) Suc was reported to promote floral transition of late-flowering mutants such as co, fca, and gi, floral transition in these mutants was delayed by a further increase in Suc concentration. These results suggest that sugar may affect floral transition by activating or inhibiting genes that act to control floral transition, depending on the concentration of sugars, the genetic background of the plants, and when the sugar is introduced. Growth on 1% (w/v) Suc did not restore the reduced expression levels of FT and SOC1/AGL20 in co or fca mutants. Rather, expression of FT and SOC1/AGL20 was repressed by 1% (w/v) Suc in wild-type background. The possible effects of sugar on gene expression to promote floral transition are discussed.

Anthocyanins↗
PubMed2001

Schedule-dependent synergism and antagonism between raltitrexed ("Tomudex") and methotrexate in human colon cancer cell lines in vitro.

The folate-dependent enzymes are attractive targets for cancer chemotherapy. Methotrexate (MTX), which inhibits dihydrofolate reductase, has been widely used for the treatment of solid tumors and hematological cancers. Raltitrexed ("Tomudex") ), which inhibits thymidylate synthase, is a novel anticancer agent active against colorectal cancer and some other solid tumors. We studied the optimal schedule of raltitrexed and MTX in combination against four human colon cancer cell lines Colo201, Colo320, LoVo, and WiDr. These cells were simultaneously exposed to raltitrexed and MTX for 24 h, or sequentially exposed to raltitrexed for 24 h followed by MTX for 24 h, or vice versa. Cell growth inhibition after 5 days was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of drug combinations at the concentrations of drug that produced 80% and 50% cell growth inhibition (IC(80) and IC(50)) were analyzed by the isobologram method (Steel and Peckham, 1979). Cytotoxic interactions between raltitrexed and MTX were schedule-dependent. The simultaneous exposure to raltitrexed and MTX showed additive effects in Colo201, LoVo and WiDr cells and antagonistic effects in Colo320 cells. The sequential exposure to raltitrexed followed by MTX produced additive effects in all four cell lines. The sequential exposure to MTX followed by raltitrexed produced synergistic effects in Colo201, LoVo and WiDr cells and additive effects in Colo320 cells. These findings suggest that the sequential administration of MTX followed by raltitrexed produces more than the expected cytotoxicity and may be the optimal schedule at the cellular level. Further in vivo and clinical studies will be necessary to determine the toxicity and to test the antitumor effects of sequential administration of MTX followed by raltitrexed proposed on the basis of the in vitro synergism.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

In vivo selection of T-cell receptor junctional region sequences by HLA-A2 human T-cell lymphotropic virus type 1 Tax11-19 peptide complexes.

Using HLA-peptide tetrameric complexes, we isolated human T-cell lymphotrophic virus type 1 Tax peptide-specific CD8(+) T cells ex vivo. Antigen-specific amino acid motifs were identified in the T-cell receptor Vbeta CDR3 region of clonally expanded CD8(+) T cells. This result directly confirms the importance of the CDR3 region in determining the antigen specificity in vivo.

Amino Acid Motifs↗
PubMed2001

Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway.

Axin acts as a negative regulator in Wnt signaling through interaction with various molecules involved in this pathway, including beta-catenin, adenomatous polyposis coli, and glycogen synthase kinase 3beta. We show here that Axin also regulates the effects of Smad3 on the transforming growth factor beta (TGF-beta) signaling pathway. In the absence of activated TGF-beta receptors. Axin physically interacted with Smad3 through its C-terminal region located between the beta-catenin binding site and Dishevelled-homologous domain. An Axin homologue, Axil (also called conductin), also interacted with Smad3. In the absence of ligand stimulation, Axin was colocalized with Smad3 in the cytoplasm in vivo. Upon receptor activation, Smad3 was strongly phosphorylated by TGF-beta type I receptor (TbetaR-I) in the presence of Axin, and dissociated from TbetaR-I and Axin. Moreover, the transcriptional activity of TGF-beta was enhanced by Axin and repressed by an Axin mutant which is able to bind to Smad3. Axin may thus function as an adapter of Smad3, facilitating its activation by TGF-beta receptors for efficient TGF-beta signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Calcium signals in rat basophilic leukemia (RBL-2H3) cells primed with the neuropeptide substance P.

Communication between nerves and mast cells is a prototypic demonstration of neuroimmune interaction. We have recently shown that direct nerve-mast cell cross-talk can occur in the absence of an intermediary transducing cell and that the neuropeptide substance P is an important mediator of this communication. Here we study the calcium signals in rat basophilic leukemia cells (RBL-2H3; mucosal-type mast cells) primed with substance P. RBL cells responded only slightly to stimulation with compound 48/80, however they responded to the stimulation when the cells had been primed with substance P (0.5 microM) for one week. The present results provide a foundation to study the neuroimmune cross-talk in a co-culture system.

Animals↗
PubMed2001

Lecithin:cholesterol acyltransferase reduces the adverse effects of oxidized low-density lipoprotein while incurring damage itself.

In this study, we tried to determine (a) whether there is any permanent effect of oxLDL on the LCAT molecule and its activator lipoprotein apoA-I, and (b) the fate of oxLDL after its exposure to LCAT and apoA-I. Purified LCAT and LDL/oxLDL was incubated at 37 degrees C for 1 h, and separated by gel-permeation chromatography. Its activity was significantly less (30% less) after separating from oxLDL compared to that of LDL. Cofactor activity of isolated apoA-I (incubated with LDL/oxLDL) was found affected by oxLDL. These results indicate modification of the LCAT and apoA-I molecule. But LCAT was found more affected compared to apoA-I in terms of LCAT activity. We are also reporting a novel function of LCAT. It was found to reduce the adverse effects of oxLDL, for example, ability to affect the LCAT activity and TBARS value. This ability of LCAT to repair oxLDL was dose-dependent. But there was no change in its REM values or fluorescence intensity.

Apolipoprotein A-I↗
PubMed2001

Endarterectomy for narrowing of the external carotid artery in a patient who underwent extracranial-intracranial bypass for occlusion of the internal carotid artery--case report.

A 56-year-old man had undergone extracranial-intracranial (EC-IC) bypass surgery for occlusion of the right internal carotid artery. Six years later, he complained of transient episodes of numbness in the left arm, occurring periodically over the previous 3 months. Neuroimaging showed the right external carotid artery was severely narrowed and cerebral blood flow (CBF) was diffusely low. Endarterectomy of the right external carotid artery was performed. Postoperative CBF was markedly improved, suggesting that EC-IC bypass became effective again by endarterectomy of a parent artery.

Carotid Artery, External↗
PubMed2001

Role of cytokines in autoimmune myocarditis and cardiomyopathy.

Cellular as well as humoral autoimmune responses are critically associated with the pathogenesis and progression of myocarditis and cardiomyopathy. Cytokines appear to play critical roles in accentuating or regulating autoimmune mechanisms in these disorders. However, depending on the triggers of autoimmune responses against the heart, such as viral or parasitic infections and experimental immunization with cardiac myosin, the effect of each cytokine on autoimmune myocardial disease may vary. Cytokines may represent new therapeutic targets in the treatment and prevention of autoimmunity-mediated myocarditis and cardiomyopathy, though the etiology and variability in the type of autoimmune responses should be taken into account in the development of cytokine/anti-cytokine treatment of these disorders.

Autoimmune Diseases↗
PubMed2001

Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers.

Accumulation of beta-catenin in cytoplasm and nuclei is frequently observed in a wide variety of tumors arising, for example, in the colon, liver, uterus, or brain. In association with Tcf/LEF transcription factors, beta-catenin regulates expression of genes involved in the Wnt/wingless signaling pathway, but the precise mechanisms are unclear. Here we report evidence that the claudin-1 (CLDNI) gene is one of the genes regulated by beta-catenin. Not only did expression of CLDN1 decrease significantly in response to reduction of intracellular beta-catenin by adenovirus-mediated transfer of wild-type APC into the APC-deficient colon cancer cells, but also two putative Tcf4 binding elements in the 5' flanking region of CLDN1 were confirmed to be responsible for activating its transcription. We documented increased expression of CLDN1 in all 16 primary colorectal cancers we examined, compared with adjacent noncancerous mucosae. Furthermore, immunohistochemical staining demonstrated that claudin-1 was weakly stained at apical boarder of lateral membrane of noncancerous epithelial cells and that it was strongly stained at all cell-cell boundaries and in the cytoplasms of cancer cells. Our results imply that claudin-1 is involved in the beta-catenin-Tcf/LEF signaling pathway, and that increased expression of claudin-1 may have some role in colorectal tumorigenesis.

Claudin-1↗
PubMed2001

[Aneurysms of the distal posterior inferior cerebellar artery--analysis of 14 aneurysms in 13 cases].

Thirteen cases of distal posterior inferior cerebellar artery (PICA) aneurysms are reported here. All the aneurysms were found after a subarachnoid hemorrhage. Dissecting aneurysm, incidentally found unruptured aneurysms, and aneurysms associated with arteriovenous malformation have been eliminated from this study. Characteristics for this type of lesion are a high rate of recurrent hemorrhage and rapid death due to direct compression of the brain stem, which clearly indicates the necessity of early surgery. Attention should be paid to the fact that angiography cannot always reveal aneurysms, especially when they are located in the peripheral PICA. One should also pay attention to multiple lesions and rapid growing acute subdural hematoma as initial findings for ruptured distal PICA aneurysm. Prognostic factors for these lesions are, vasospasm, especially when the aneurysm is located proximally in the PICA, and direct compression of the brain stem due to intraventricular hemorrhage when the aneurysm is located distally. It has been suggested that the pathogenesis of this lesion could be hemodynamic stress or embryogenesis. The shape and anomalous arterial structures of the 14 aneurysms presented here tend to agree with this suggestion. Our results suggest that the pathogenesis is hemodynamic stress that had developed due to embryological and/or arteriosclerotic factors.

Adult↗
PubMed2001

[A case of aneurysm of the peripheral middle cerebral artery undetectable on preoperative angiogram].

The authors describe a rare case of an aneurysm of the peripheral middle cerebral artery. A 63-year-old female with a past history of hypertension suddenly fell into a comatose state, and was brought to our hospital. On admission, CT scan showed intracerebral hematoma located in the right putamen with diffuse subarachnoid hemorrhage. To exclude vascular lesions, an angiography was performed just after admission. The right carotid angiogram showed an aneurysm at the cavernous portion of the internal carotid artery (ICA), but failed to show any aneurysms in the rest of the intracranial circulation. Just after the angiography, emergent operation was performed for the main purpose of evacuation of the hematoma, and with only the secondary purpose of searching for undetectable aneurysms. The patient underwent a right frontotemporal craniotomy. After partial evacuation of the hematoma through the corticotomy of the right frontal operculum, the Sylvian fissure was opened widely. No aneurysm was observed either in the main trunk of the right ICA or the middle cerebral artery (MCA). During the final stage of evacuation of the hematoma through the corticotomy, arterial bleeding occurred. While evacuating the blood, we detected a saccular aneurysm arising from MCA branch (M2-M3 junction) and we clipped the aneurysm. We discuss peripheral MCA aneurysms with a review of the literature.

Cerebral Angiography↗
PubMed2001

[Craniopharyngioma with rapid regrowth--role of MIB-1 labeling index].

The treatment of craniopharyngioma becomes quite difficult when it extends into the third ventricle. In a 4-year-old boy, we encountered a large cystic craniopharyngioma which grew into the third ventricle. Initially, the tumor was successfully removed via a right transcallosal transchoroidal approach. A residual part seemed to have remained in the right perioptic region. Even though the patient had an episode of SIADH, his postoperative course was uneventful. He developed visual disturbance 4 months after the initial operation. CT and MRI revealed a large suprasellar mass. The tumor was totally resected via a right pterional approach. Careful follow-up disclosed again a small recurrent lesion in the anterior commisure. Gamma knife therapy was used to successfully reduce the volume of the tumor. The MIB-1 labeling index (LI) of the specimen taken at the time of the first operation was at 9.2% and that of the second operation at 21.2%. Recently, the importance of MIB-1 LI for assessing proliferative activity of this tumor was reported. In patients whose MIB-1 LI is higher, they have more significant rate of recurrence. Our results also indicate that in cases where MIB-1 LI indicates a high value, careful follow-up is necessary. Through fact of the necessity of two operations and additional gamma knife therapy, we would like to stress the importance of MIB-1 LI in indicating the proliferative activity of this tumor. These surgical procedures are presented here, and the role of MIB-1 LI in determining the proliferative activity of craniopharyngioma is also discussed.

Antigens, Nuclear↗