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Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

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

[A study on cervical reflex induced by click stimuli in cats].

UNLABELLED: The effects of click stimuli on the cervical muscle have been wildly studied, but no information is available on what reaction click stimuli elicit from the cervical cord. We studied the effects of click stimuli on the cervical cord in cats. PURPOSE: To determine the response of the cervical cord to click stimuli in cats. MATERIALS AND METHODS: Subjects were ten adult cats confirmed to have normal tympanic membranes. Cats were placed on artificial ventilation by tracheal incision. Auditory brainstem response (ABR) of both ears was measured to determine its threshold. Following the cervical incision, the dorsal vertebrae were removed, the cervical cord was exposed at C3 to C6, and bipolar needle electrodes were inserted. The reference electrode was attached to the forehead. Click stimuli were presented using 1-20 Hz clicks. RESULTS: Responses peaking at 4.89-5.10 ms were induced by click stimuli of 105 dBSPL (1 Hz) at C3. Latencies tended to be prolonged with decreasing sound pressure. No response was confirmed at of C4 to C6. The responses to clicks of 20 Hz or more disappeared when 100 responses were summed. After the experiment, we confirmed that accessory nerves showed a response to electrical stimuli applied by bipolar needle electrodes. The cervical cord was removed to make sure that the electrode had been passed into the spinal nucleus of the accessory nerve. DISCUSSION: Spinal nuclei of accessory nerves exist at C3 to C5 of the cervical cord, and are associated with the movement of the sternocleidomastoid muscle at C3 in particular. Click stimuli are reported to affect the sternocleidomastoid muscle. The results of our study appear to reflect the response of the spinal nucleus of the accessory nerve to click stimuli. The fact that responses to clicks of 20 Hz or more disappeared when 100 responses were summed suggests that the response was induced via a pathway other than the auditory pathway.

Acoustic Stimulation↗
PubMed2001

RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum.

The retinoblastoma protein interacting zinc finger (RIZ) gene is a candidate tumor suppressor gene on 1p36, a region frequently rearranged in a wide variety of human tumors. As the RIZ gene harbors several microsatellites within its coding region, it is a candidate for an inactivating mutation in microsatellite instability (MSI) mediated carcinogenesis. In this study, we examined mutations of two poly adenine tracts, A(8) and A(9), within the coding region of the RIZ gene, in MSI-high (MSI-H) primary cancers occurring in the pancreas, stomach, and colorectum. Frameshift mutations were found in one (10%) of 10 pancreatic, four (36%) of 11 gastric, and two (25%) of eight colorectal cancers. These results indicate that mutations of the RIZ gene play an important role in the pathogenesis of some MSI-H cancers.

Colorectal Neoplasms↗
PubMed2001

Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemia K562 cells.

Coproporphyrinogen oxidase (CPOX), the sixth enzyme in the heme-biosynthetic pathway, catalyzes oxidative decarboxylation of coproporphyrinogen to protoporphyrinogen and is located in the intermembrane space of mitochondria. To clarify the importance of CPOX in the regulation of heme biosynthesis in erythroid cells, we established human erythroleukemia K562 cells stably expressing mouse CPOX. The CPOX cDNA-transfected cells had sevenfold higher CPOX activity than cells transfected with vector only. Expression of ferrochelatase and heme content in the transfected cells increased slightly compared with the control. When K562 cells overexpressing CPOX were treated with delta-aminolevulinic acid (ALA), most became benzidine-positive without induction of the expression of CPOX or ferrochelatase, and the heme content was about twofold higher than that in ALA-treated control cells. Increases in cellular heme concomitant with a marked induction of the expression of heme-biosynthetic enzymes, including CPOX, ferrochelatase and erythroid-specific delta-aminolevulinic acid synthase, as well as of alpha-globin synthesis, were observed when cells were treated with transforming growth factor (TGF)beta 1. These increases in the transfected cells were twice those in control cells, indicating that overexpression of CPOX enhanced induction of the differentiation of K562 cells mediated by TGF beta 1 or ALA. Conversely, the transfection of antisense oligonucleotide to human CPOX mRNA into untreated and TGF beta 1-treated K562 cells led to a decrease in heme production compared with sense oligonucleotide-transfected cells. These results suggest that CPOX plays an important role in the regulation of heme biosynthesis during erythroid differentiation.

Aminolevulinic Acid↗
PubMed2001

[Legal settlements of medical accidents].

When an accident occurs during the course of clinical treatment, it is important to record the series of events as objectively as and in the most precise detail possible. The causes of the accident should be investigated with all due speed, and an accurate, consistent account should be rendered to the patient's family. When the cause of a patient's death is not clear, a pathological autopsy should be performed. It is the legal responsibility of physicians to notify the police of unexpected death when medical malpractice is suspected, and in compliance with the law an autopsy must be performed. A malpractice suit brought against a medical institution can be settled by two means: out-of-court settlement; and court decision. An out-of-court settlement in the event of obvious medical error is the more desirable option from the viewpoint of immediate relief of patients and/or ther families. At present, an average of three years elapses before a medical malpractice suit can be resolved in the courts. One of the main reasons for this delay in the settlement of court case is the difficulty in obtaining competent expert witnesses, and therefore members of the Japan Surgical Society should cooperate actively with the legal authorities in medical malpractice suits.

Japan↗
PubMed2001

[MR hydrography of the abdomen: technical consideration of data acquisition and future prospects for clinical applications].

Recent advances in MR hydrography have enabled various clinical applications in the areas of abdominal and pelvic disorders, for example, MR cholangiopancreatography (MRCP), MR urography(MRU), and MR hydrography of the fetus. Although the two-dimensional(2D) single-slice method provides excellent information as to the global relationship between lesions and various anatomical structures, small lesions or detailed anatomical characteristics may not be visualized owing to the partial volume effect. Source images of the 2D multislice method are most suitable for the detection of small lesions and detailed evaluation of anatomical structures as "tomographic imaging", while the three-dimensional(3D) method is useful in obtaining data sets for 3D imaging. MR hydrography is a promising method for the noninvasive evaluation of various abdominal disorders, and it has the potential to play new roles in various anatomical regions. However, knowledge of the proper indications is essential for successful clinical application.

Abdomen↗
PubMed2001

["Unusual death" in relation to the clinical practice].

Japan Surgical Society has made a declaration about patients' "unusual death" which incidentally occurred in their clinical courses, in reference to the practitioners' duty to notify the police under Article 21 of the Medical Act. The meanings of this declaration could be summarized in three points. Firstly, it confirms opportunities to reveal evident medical malpractices causing patients' deaths by affirming the duty in the cases it is suspected that patients' deaths were caused by evident medical malpractices. Secondly, it requires impartial inquiries to judge negligence about anticipated complications after surgery by denying the duty in the cases that patients died as results of anticipated complications after surgery. Thirdly, it proposed establishment of a generalized system to be noticed about medical malpractices causing patients' injuries irrespective of causing patients' deaths and to collect data concerning small incidents and risks in medical practice. The society would start to make a detailed guideline of "unusual death" in relation to the clinical practice. However, such a guideline should be made as an applicable one for that of the malpractices which practitioners are obliged to report under the generalized system.

Death↗
PubMed2001

[Analysis of chimerism in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation].

Serial monitoring of chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) can be performed easily and rapidly using PCR-based assays analyzing informative tandem repeat genetic markers. Sequential analysis of individual chimerism status was performed in 34 patients who underwent myeloablative allo-HSCT using a commercial multiplex short tandem repeat (STR) kit. Mixed chimerism (MC) was found in 14 of the patients for more than one month. The incidence of MC seemed to be dependent on the type of disease or pretransplantation regimen. There was no significant difference in relapse rates between MC and complete donor chimerism (CC) in all patients. However, the relapse rate was significantly higher in MC than in CC among patients with acute leukemia. The severity of acute graft-versus-host disease (aGVHD) was significantly reduced in the patients with MC. Most of the MC patients with hematologic malignancies had transient mixed T-lymphoid chimerism, and CC was achieved within 6 months after HSCT in such cases. Patients with MC beyond 6 months after HSCT and patients with reappearance of autologous signals (MC after CC) may have an enhanced risk of relapse.

Adolescent↗
PubMed2001

[Preoperative PDT for early stage lung cancer accompanied with infiltration to the central airway].

For the treatment of central type lung cancers, it is often necessary to perform bronchoplasty or bi-lobectomy even in early stage cases in which tumor invasion is found at the bronchial bifurcation. To solve this contradictory situation, we applied PDT for central type early stage lung cancer to reduce the extent of superficial infiltration, enabling a simple surgical technique or decreasing the amount of resected lung parenchyma. Among 7 patients, the simplification of surgical technique and reduction of the range of resection were possible in 2 cases each respectively. However, these objectives were not satisfied in the remaining 3 cases and the operations performed were those that had been originally scheduled before PDT. The current problems are the establishment of appropriate laser irradiation technique and accurate assessment for extension of invasion.

Adult↗
PubMed2001

Prognostic significance of multidrug resistance protein in adult T-cell leukemia.

The response of adult T-cell leukemia (ATL) to chemotherapy is poor, and a major obstacle to successful treatment is intrinsic or acquired drug resistance. To determine the clinical significance of multidrug resistance protein (MRP) 1 in ATL, we studied MRP1 expression and its association with clinical outcome. The expression of MRP1 mRNA in leukemia cells from 48 ATL patients was studied by slot blot analysis. The expression level of MRP1 mRNA in chronic-type ATL was significantly higher than that in lymphoma-type ATL (P = 0.033). There was no correlation between MRP1 expression and age, gender, WBC count, LDH, hypercalcemia, blood urea nitrogen, or performance status. However, the expression of MRP1 mRNA correlated only with peripheral blood abnormal lymphocyte counts (P = 0.008). The transporting activity of MRP1 was assessed using membrane vesicles. Membrane vesicles prepared from ATL cells with high expression of MRP1 mRNA showed a higher ATP-dependent leukotriene C(4) uptake than did those with low expression of MRP1 mRNA. This uptake was almost completely inhibited by LTD(4) antagonists ONO-1078 and MK571. In acute- and lymphoma-type ATL, high expression of MRP1 mRNA at diagnosis correlated with shorter survival, and Cox regression analysis revealed that MRP1 expression was an independent prognostic factor. These findings suggest that functionally active MRP1 is expressed in some ATL cells and that it is involved in drug resistance and has a possible causal relationship with poor prognosis in ATL. Multidrug resistance-reversing agents, such as ONO-1078 and MK571, that directly interact and inhibit the transporting activity of MRP1 may be useful for treating ATL patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach.

Although the sentinel node (SN) concept has been validated in malignant melanoma and breast cancer, the application of this concept for other solid tumors, including gastrointestinal (GI) cancer, is still controversial. We have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric, and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastasis from the primary lesion were detectable using this method. More recently, we have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimized the identification of SNs that drained GI cancers. Our preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis, and we believe that it will become an important component of a minimally invasive approach to early-stage GI cancers.

Colonic Neoplasms↗
PubMed2001

[Clinical significance of sentinel node navigation surgery in the treatment of early gastric cancer].

Radical lymphadenectomy is the standard surgical approach even for early-stage gastric cancer with a relatively low incidence of lymph node metastasis because of the limited sensitivity of diagnostic imaging to detect micrometastasis in regional lymph nodes. The sentinel node (SN) concept is one topic among novel diagnostic procedures for micrometastasis. The SN is defined as the first draining node from the primary lesion and it would be the first site of micrometastasis. SN biopsy has been clinically validated and applied for the surgical treatment of malignant melanoma and breast cancer. Although the feasibility of this technique in other solid tumors including gastric cancer is still controversial, there are several reports demonstrating the diagnostic significance of SN mapping in early gastric cancer. We have established radio-guided SN mapping for early gastric cancer, and the diagnostic accuracy using this procedure in cT1N0 cases reached 98%. The radio-guided method allows us to detect the SN in endoscopic surgery quantitatively and reproducibly. Validation of the SN concept in gastric cancer in a multi-centric clinical trial is essential for clinical application of this procedure, including the establishment of a novel, minimally invasive approach for early-stage gastric cancer.

Humans↗
PubMed2001

[A case of convergence spasm in hysteria improved with a brief psychiatric assessment].

We report a 16-year-old female who developed double vision. The diplopia was in the horizontal plane and persisted for 3 weeks. She also complained of headache and nausea. She kept her eyes closed unless she was told to open. When eyelids were passively open, both eyes deviated inward in an adducted position. The pupil size and the reaction to light were normal. No weakness was noted in the extraocular muscles when each eye was examined individually. The rest of the neurologic examinations were normal. We thought that she had a convergence spasm. Brain CT and MRI were normal. The CSF and blood chemistries were also normal. We treated her with supportive psychotherapy and her convergence spasm disappeared. We concluded that her convergence spasm was a manifestation of conversion hysteria.

Adolescent↗
PubMed2000

Differential effects of leukocyte common antigen-related protein on biochemical and biological activities of RET-MEN2A and RET-MEN2B mutant proteins.

Protein-tyrosine-phosphatases (PTPs), in conjunction with protein-tyrosine kinases, play essential regulatory roles in diverse cellular activities by modulating the phosphorylation state of target proteins. Leukocyte common antigen-related (LAR) protein is a widely expressed receptor-type protein-tyrosine-phosphatase that is implicated in the regulation of intracellular signaling triggered by both cell adhesion and peptide growth factors. The gene for LAR is localized to human chromosome 1p32, a region frequently deleted in tumors of neuroectodermal origin, including neuroblastoma, pheochromocytoma, and medullary thyroid carcinoma. On the other hand, the RET gene codes for a transmembrane tyrosine kinase and is responsible for the development of multiple endocrine neoplasia (MEN) 2A and 2B. To explore the potential role of LAR in RET tyrosine kinase activity and RET-induced signal transduction, we cotransfected LAR and RET with a MEN2A or MEN2B mutation (designated RET-MEN2A or RET-MEN2B) into the NIH 3T3 cell line. Here we show that LAR reduces the constitutive tyrosine autophosphorylation and kinase activity of RET-MEN2A but not RET-MEN2B, accompanying a significant decrease of phosphorylation of phospholipase Cgamma, AKT, and ERK1/2. Interestingly, LAR expression significantly decreased the levels of disulfide-linked RET-MEN2A dimerization. Moreover, reduced oncogenic activity of RET-MEN2A by overexpression of LAR was observed both by an in vitro colony formation assay and by in vivo tumorigenicity in scid mice. These results thus suggest that LAR may contribute to deactivation of the RET-MEN2A mutant protein and reduction of its oncogenic activity in vivo.

3T3 Cells↗
PubMed2000

Apoptosis and cell proliferation in esophageal sqamous cell carcinoma treated by chemotherapy.

The p53 gene is associated with G1 arrest during the cell cycle and with apoptosis. To evaluate the preoperative chemotherapeutic effect in esophageal squamous cell carcinoma, we retrospectively investigated the apoptotic index (AI) and Ki-67 labeling index (Ki-67LI) in relation to the expression of p53. Thirty patients with esophageal carcinoma who had received chemotherapy prior to surgery were examined using the terminal deoxynucleotidyl-transferase-mediated in-situ end-labeling (TUNEL) method for evaluating AI and immunohistochemical staining with anti Ki-67 and anti p53 antibody for evaluating Ki-67LI and p53 expression, respectively. The histological response rate of chemotherapy was 20.0%. A significant correlation between p53-negative expression and response to chemotherapy was found (P<0. 01). The AIs and Ki-67LIs in p53-negative tumors with ineffective responses to chemotherapy were significantly higher than those in p53-positive tumors with ineffective responses (P<0.05). The AIs and Ki-67LIs were significantly lower in p53-negative tumors with effective responses to chemotherapy than those in p53-negative tumors with ineffective responses (P<0.05 and P<0.01, respectively). Furthermore, significant correlations were found between AIs and Ki-67LIs in p53 negative tumors (r=0.60, P<0.05). In esophageal carcinoma, p53-negative tumors with highly proliferative cells might be susceptible to apoptosis induced by chemotherapy.

Adult↗
PubMed2000

Assembly of partial TFIID complexes in mammalian cells reveals distinct activities associated with individual TATA box-binding protein-associated factors.

The TATA box-binding protein (TBP) and TBP-associated factors (TAF(II)s) compose the general transcription factor TFIID. The TAF(II) subunits mediate activated transcription by RNA polymerase II by interacting directly with site-specific transcriptional regulators. TAF(II)s also participate in promoter recognition by contacting core promoter elements in the context of TFIID. To further dissect the contribution of individual TAF(II) subunits to mammalian TFIID function, we employed a vaccinia virus-based protein expression system to study protein-protein interactions and complex assembly. We identified the domains of human (h) TAF(II)130 required for TAF(II)-TAF(II) interactions and formation of a complex with hTBP, hTAF(II)100, and hTAF(II)250. Functional analysis of partial TFIID complexes formed in vivo indicated that hTAF(II)130 was required for transcriptional activation by Sp1 in vitro. DNase I footprinting experiments demonstrated that purified hTBP/hTAF(II)250 complex reconstituted with or without additional TAF(II)s was significantly reduced for TATA box binding (as much as 9-fold) compared with free hTBP. By contrast, hTAF(II)130 stabilized binding of hTBP to the TATA box, whereas hTAF(II)100 had little effect. Thus, our biochemical analysis supports the notion that TAF(II)s possess distinct functions to regulate the activity of TFIID.

Cell Line↗
PubMed2000

Characterization of S818L mutation in HERG C-terminus in LQT2. Modification of activation-deactivation gating properties.

We examined the mechanism(s) for HERG channel dysfunction in an S818L mutation in the HERG C-terminus using the heterologous expression system in Xenopus oocytes. Injection of S818L cRNA alone did not produce expressed currents. Coinjection of an equal amount of S818L cRNA with wild-type (WT) cRNA into oocytes did not exhibit apparent dominant-negative suppression. However, coinjection of excess amounts of S818L cRNAs with WT cRNA into oocytes decreased HERG current amplitudes and shifted the voltage dependence of activation to negative potentials, accelerated its activation and deactivation. The data suggest that S818L alone cannot form functional channels, whereas S818L subunits can, at least in part, coassemble with WT subunits to form heterotetrameric functional channels, and imply that the HERG C-terminus may contain a domain involving the activation-deactivation process of the channel. These findings may provide new insights into the structure-function relationships of the HERG C-terminus.

Amino Acid Substitution↗