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Biomedical subjects

A Kawai

Publications and source records attributed to A Kawai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Development of acute myeloid leukemia after chemotherapy for osteosarcoma.

The current study describes two patients with osteosarcoma who had acute myeloid leukemia develop after treatment with multiagent chemotherapy. The incidence density for the chemotherapy protocol was 129.8 per 10,000 person-year of followup. Karyotype analysis of 16 reported patients (including the current two patients) indicated that most leukemias after treatment of osteosarcoma correlated with the use of topoisomerase II inhibitors, such as doxorubicin. The deoxyribonucleic acid-damaging activity of doxorubicin reinforced by the use of alkylating agents is highly suspected as a causative event in the development of leukemia after treatment of osteosarcoma. As the next step in the development of treatment for patients with osteosarcoma, the type and intensity of treatment must be evaluated to minimize possible leukemogenic effects without compromising the potential for cure.

Acute Disease↗
PubMed2001

Dynamic magnetic resonance imaging of femoral head perfusion in femoral neck fracture.

A prospective followup study of 36 femoral neck fractures according to the assessment of femoral head perfusion using dynamic magnetic resonance imaging is reported. Patients were divided into three groups based on the dynamic magnetic resonance imaging findings (dynamic curve pattern and relative enhancement ratio) that were conducted within 48 hours of the injury. Traction was used to achieve anatomic reduction and to prevent additional damage to vascularity until minimally invasive internal fixation could be done. The fractures of all 17 patients whose femoral head perfusion was normal (Type A; n = 11) or was impaired but not totally absent (Type B; n = 6) healed without complications. Among the 19 patients whose femoral head perfusion was absent (Type C), 15 had complications (osteonecrosis, n = 10; nonunion, n = 5). Assuming that fractures with a Type A or Type B curve pattern would unite successfully and that those with a Type C curve pattern would not, the sensitivity, specificity, and accuracy of the predictions of successful osteosynthesis of the femoral neck fractures using this method were 81%, 100%, and 89%, respectively. The current classification of femoral neck fractures using dynamic magnetic resonance imaging may be useful in selecting an appropriate treatment method for the fractures.

Adult↗
PubMed2001

Effects of mutation in hepatitis C virus nonstructural protein 5A on interferon resistance mediated by inhibition of PKR kinase activity in mammalian cells.

The IFN-induced double-stranded RNA (dsRNA)-activated protein kinase PKR is one of the key molecules in the antiviral effects of IFN. To clarify the effects of hepatitis C virus nonstructural protein 5A (NS5A) on antiviral activity of IFN, in particular on PKR kinase activity, in mammalian cells, we established inducible NS5A-expressing cell lines derived from human osteosarcoma (Saos-2). The cells expressing NS5A derived from an IFN-resistant clone (NS5A-lb) that interacted with endogenous PKR in vitro, showed a suppressive effect on IFN function as determined by interference with vesicular stomatitis virus (VSV) infection, whereas NS5A (NS5A-2a) from an IFN-sensitive clone did not block the antiviral effect of IFN. A mutant with deletion of the IFN sensitivity determining region (ISDR) in NS5A-1b (NS5A-AISDR) also interacted with PKR and suppressed its activity in vitro. However, neither NS5A-2a nor the C-terminal truncated mutant of NS5A-1b (NS5A-deltaC) blocked PKR activity. These observations confirmed the previous report that the inhibitory effect of NS5A on IFN activity is mediated at least in part by the repression of PKR. In addition, we showed that IFN sensitivity was determined not only by the ISDR but that the involvement of the C-terminal region of NS5A-1b is important for the suppression of PKR activity.

Amino Acid Sequence↗
PubMed2001

Loss of the mitochondrial Hsp70 functions causes aggregation of mitochondria in yeast cells.

Ssc1p, a member of the Hsp70 family in the mitochondrial matrix of budding yeast, mediates protein import into mitochondria and prevents irreversible aggregation of proteins in the mitochondrial matrix during folding/assembly or at elevated temperature. Here, we show that functional inactivation of the mitochondrial Hsp70 system causes aggregation of mitochondria. When temperature-sensitive mitochondrial Hsp70 mutant cells were incubated at restrictive temperature, a tubular network of mitochondria was collapsed to form aggregates. Inhibition of protein synthesis in the cytosol did not suppress the mitochondrial aggregation and functional impairment of Tim23, a subunit of mitochondrial protein translocator in the inner membrane, did not cause mitochondrial aggregation. Therefore defects of the Hsp70 function in protein import into mitochondria or resulting accumulation of precursor forms of mitochondrial proteins outside the mitochondria are not the causal reason for the aberrant mitochondrial morphology. By contrast, deletion of Mdj1p, a functional partner for mitochondrial Hsp70 in prevention of irreversible protein aggregation in the matrix, but not in protein import into mitochondria, caused aggregation of mitochondria, which was enhanced at elevated temperature (37 degrees C). The aggregation of mitochondria at 37 degrees C was reversed when the temperature was lowered to 23 degrees C unless protein synthesis was blocked. On the basis of these results, we propose that the mitochondrial matrix contains a protein that is responsible for the maintenance of mitochondrial morphology and requires mitochondrial Hsp70 for its function.

Actins↗
PubMed2001

[Postoperative rupture of abdominal aortic aneurysm in patients with ischemic heart disease and other organ disease].

We experienced two cases of rupture of an abdominal aortic aneurysm during the early postoperative period of coronary artery bypass grafting (CABG). A 71-year-old man on hemodialysis (HD) was diagnosed with ischemic heart disease (IHD) and abdominal aortic aneurysm (AAA) of 70 mm in size. After CABG, he developed symptoms of acute pancreatitis and died of rupture of AAA on the 12th postoperative day. A 74-year-old man with early gastric cancer was diagnosed with IHD and AAA of 70 mm. After CABG and gastrectomy, he died of rupture of AAA due to anticoagulant therapy on the 3rd postoperative day. One-stage operation should be performed in patients with IHD, AAA more than 60 mm in size and other organ disease. It is important to control blood pressure and anticoagulant therapy appropriately during the early postoperative period when graft replacement for AAA is not performed simultaneously. Careful observation is required to establish the differential diagnosis of acute pancreatitis and impending rupture of AAA in patients on HD.

Aged↗
PubMed2001

[Cardiovascular effects of colforsin daropate hydrochloride for acute heart failure after open heart surgery].

Colforsin daropate hydrochloride (COL) is a novel drug for the treatment of acute heart failure. COL stimulates adenylate cyclase directly and produces positive inotropic and vasodilator effects accompanied by the increase in cellular cAMP. We investigated its cardiovascular effects for 9 patients who showed low cardiac index (< 3.0 l/min/m2) after open-heart surgery in ICU. After 2 or 3 hours from administration of COL, heart rate and cardiac index increased, and pulmonary artery pressure and central venous pressure decreased significantly, but blood pressure and systemic venous oxygen saturation did not show significant change. In conclusion, COL improved hemodynamics through positive inotropic and vasodilator effects without hypotension. We should investigate more proper usage of this drug to avoid such side effects as tachycardia and arrhythmia, which occurred in some cases.

Acute Disease↗
PubMed2000

A reverse transcriptase-polymerase chain reaction assay in the diagnosis of soft tissue sarcomas.

BACKGROUND: Many types of sarcomas are characterized by specific chromosomal translocations that result in the production of novel chimeric genes. Detection of these fusion genes could be a sensitive molecular diagnostic assay. However, to the authors' knowledge there have been few systemic comparisons between the current histopathologic diagnosis and the presence or absence of particular fusion genes in patients with adult soft tissue sarcomas (STSs). METHODS: Total RNA was extracted from 75 cases of STS and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of a variety of fusion transcripts. The results of the molecular assay were compared with standard histopathologic diagnoses. RESULTS: Of the 18 tumors diagnosed as synovial sarcoma, 17 (94%) expressed SYT-SSX chimeric transcripts. All nine myxoid liposarcomas were positive for FUS-CHOP fusion transcripts. Of the four cases of Ewing sarcoma, two had an EWS-FLI1 fusion transcript and one had an EWS-ERG fusion transcript. A clear cell sarcoma had a EWS-ATF1 fusion transcript. None of 19 cases of malignant fibrous histiocytoma nor 3 leiomyosarcomas contained a fusion transcript. Three cases with an initial diagnosis other than synovial sarcoma expressed a SYT-SSX fusion transcript. A review of the slides and additional examination showed that a diagnosis of synovial sarcoma was appropriate for these cases. There was a trend for biphasic synovial sarcoma to contain the SYT-SSX1 fusion. CONCLUSIONS: The authors believe RT-PCR assay for the detection of a specific fusion gene provides a useful tool for confirmation of the diagnosis of adult STS in diagnostically difficult cases and in retrospective studies.

DNA Primers↗
PubMed2000

Three types of putative presympathetic neurons in the rostral ventrolateral medulla studied with rat brainstem-spinal cord preparation.

To study the electrophysiological properties of presympathetic neurons in the rostral ventrolateral medulla (RVLM), intracellular recordings were performed by the whole-cell patch-clamp technique. We utilized the neonatal rat brainstem-spinal cord preparation, in which the sympathetic neuronal network is thought to be preserved, unlike in slice preparation. In response to stimulation in the ipsilateral Th2 spinal segment including intermediolateral cell column (IML), 33 of 151 non-respiratory RVLM neurons showed antidromic action potentials with a constant latency of 45 ms, and can be considered as presympathetic neurons. We classified and characterized the RVLM presympathetic neurons into three types: 'regularly firing neurons (n=7)', which showed ramp depolarization and frequent action potentials (4.2+/-0.9 spikes/s) with rare excitatory postsynaptic potentials (EPSPs); 'irregularly firing neurons (n=21)', which exhibited many EPSPs that modulated the firing rate; and 'silent-type neurons (n=5)', which discharged action potentials only during current-induced depolarization. Lucifer-Yellow staining showed that the irregularly firing neurons were significantly larger and had more dendrites than the regularly firing neurons. All regularly firing neurons retained their discharges during low-Ca2+ -high-Mg2+ superfusion that blocks synaptic input, whereas the discharges in 11 of 16 irregularly firing neurons were abolished, suggesting that the regularly firing neurons discharged independently of synaptic input. Seven of 31 RVLM neurons were hyperpolarized by stimulation of vagal afferent nerves. In summary, three types of RVLM presympathetic neurons were characterized by the patch-clamp technique in the brainstem-spinal cord preparation, in which the connection was preserved from vagal afferent to the Th2 spinal segment through the RVLM. Since antidromic action potentials were demonstrated by stimulation in the Th2 spinal segment in 33 neurons of all three types, all types of RVLM neurons constitute a part of the sympathetic neuronal network.

Action Potentials↗
PubMed2000

Expression of connective tissue growth factor in cartilaginous tumors.

BACKGROUND: Connective tissue growth factor (CTGF) predominantly is expressed in hypertrophic chondrocytes and its specific receptors are demonstrated on chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or differentiation of cartilage cells. In the current study, CTGF expression was examined both in chondrosarcoma and enchondroma to clarify the relation between the expression of CTGF and the grade of malignancy. METHODS: The expression of CTGF and proliferating cell nuclear antigen (PCNA) were analyzed immunohistochemically in 34 cartilaginous tumor specimens. Eighteen tumors were determined to be chondrosarcoma including 8 Grade 1 tumors, 6 Grade 2 tumors, and 4 Grade 3 tumors. The percentage of CTGF positive and PCNA positive cells was quantified using at least 500 cells. RESULTS: CTGF was expressed in 70.1% of enchondroma cells, 84.0% of Grade 1 chondrosarcoma cells, 53.7% of Grade 2 tumor cells, and 26.8% of Grade 3 tumor cells (rho = -0.501; P = 0.0053). In chondrosarcoma cases, CTGF expression was correlated closely with tumor grade (rho = -0.920; P = 0.0001). There was a strong correlation between PCNA expression and tumor grade (rho = 0.907; P < 0.0001) and a strong negative correlation between CTGF and PCNA expression (rho = -0.493; P = 0.0061). In chondrosarcoma cases, patients with high expression of CTGF (>/= 30%) showed higher overall survival compared with those with low expression (< 30%) (P = 0.004). CONCLUSIONS: The current study revealed a correlation between the histologic grade of chondrosarcoma and prognosis, and the concomitant association between CTGF immunostaining and tumor grade and prognosis. Therefore, immunohistochemical staining with CTGF is a useful procedure for assessing the tumor grade and clinical course in patients with chondrosarcoma.

Adolescent↗
PubMed2000

The mammalian peroxin Pex5pL, the longer isoform of the mobile peroxisome targeting signal (PTS) type 1 transporter, translocates the Pex7p.PTS2 protein complex into peroxisomes via its initial docking site, Pex14p.

In mammals, two isoforms of the peroxisome targeting signal (PTS) type 1 receptor Pex5p, i.e. Pex5pS and Pex5pL with an internal 37-amino acid insertion, have previously been identified. Expression of either type of Pex5p complements the impaired PTS1 import in Chinese hamster ovary pex5 mutants, but only Pex5pL can rescue the PTS2 import defect noted in a subgroup of pex5 mutants such as ZP105. In this work, we found that Pex5pL directly interacts with the PTS2 receptor Pex7p, carrying its cargo PTS2 protein in the cytosol. Pex5pL, but not Pex5pS, mediated the binding of PTS2 protein to Pex14p by translocating Pex7p, demonstrating that Pex5pL plays a pivotal role in peroxisomal PTS2 import. Pex5p was localized mostly in the cytosol in wild-type CHO-K1 and Pex14p-deficient mutant cells, whereas it accumulated in the peroxisomal remnants in cell mutants defective in Pex13p or the RING family peroxins such as Pex2p and Pex12p. Furthermore, overexpression of Pex14p, but not Pex10p, Pex12p, or Pex13p, caused accumulation of Pex5p in peroxisomal membranes, with concomitant interference with PTS1 and PTS2 import. Therefore, Pex5p carrying the cargoes most likely docks with the initial site (Pex14p) in a putative import machinery, subsequently translocating to other components such as Pex13p, Pex2p, Pex10p, and Pex12p.

Animals↗
PubMed2000

Interaction of albumin mRNA with proteins from rat liver with CCl(4)-induced injury.

Acute phase responses to intragastric administration of a single dose of CCl(4) were examined with albumin mRNA turnover as a marker. Based on the combination of the changes in stability of albumin mRNA and activity of transcription of its gene, the entire course of liver injury was classified into three stages, the first stage for aggravation of injury until 9 h, the second from 9 to 24 h, and the third for repair of injury or regeneration of liver after 48 h. Liver S100 fractions from normal and CCl(4)-treated rats contained, in total, 11 polypeptides cross-linked with part of albumin mRNA, although they did not appear to be specific to this mRNA. Their profiles were altered together with the changes in stability of albumin mRNA in different stages. These findings suggest that the polypeptides with distinct properties play roles in physiologically significant processes involved in utilization and turnover of albumin mRNA, apparently altering its stability.

Acute-Phase Reaction↗
PubMed2000

Recurrent pulmonary adenoid cystic carcinoma presenting as a cardiac tumor.

A 58-year-old patient is presented who had a pulmonary adenoid cystic carcinoma which recurred 10 years after sleeve left pneumonectomy. The patient developed acute heart failure because the lesion obstructed blood flow by compressing the left atrium. Transesophageal echocardiography and magnetic resonance imaging demonstrated a solid mass arising from the pericardium which displaced the posterior wall of the left atrium. The mass was resected. Postoperative radiation was not performed.

Carcinoma, Adenoid Cystic↗
PubMed2000

Synovial sarcoma with a large hematoma in the inguinal region.

We report the case of a patient with synovial sarcoma and a large hematoma of the inguinal region. The patient underwent tumor resection of the lower 2/3 of the acetabulum after preoperative chemotherapy. Twenty-four months after surgery, she is alive without any relapse and can walk without support.

Acetabulum↗
PubMed2000

CD44 expression in soft tissue sarcomas.

Recent studies have shown that expression of alternatively splicing variants of CD44 is correlated with prognosis for several kinds of malignant tumors. However, little is known about the expression of CD44 standard and variant isoforms in soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression pattern of CD44H and CD44 variant exons and assessed the relation between expression of CD44s and metastasis-free survival rates (MFSR) of patients with soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and v9 (9/47) are relatively common types of variant isoforms in soft tissue sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free survival of patients with soft tissue sarcomas.

Adolescent↗
PubMed2000

Inhibitory effect of TMK-688 on late asthmatic responses as well as T-cell and eosinophilic infiltration in guinea pigs with asthmatic reactions.

The effects of an oral anti-allergic agent, TMK-688, which inhibits 5-lipoxygenase, at doses of 3.2 and 10 mg/kg were studied in guinea pigs with dual-phase asthmatic response. We previously observed that pretreatment with TMK-688 inhibited the late asthmatic response (LAR) induced by ovalbumin inhalation exposure. The present study focused on the effect of TMK-688 on infiltration by T-cells and eosinophils. TMK-688 inhibited both T-cell and eosinophilic infiltration. These findings suggest that TMK-688 is effective in inhibiting infiltration of T-cells and eosinophilic chemotaxis, and thereby suppresses LAR.

Animals↗
PubMed2000

Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma.

Synovial sarcoma is characterized by a specific recurrent translocation t(X; 18), resulting in either the SYT-SSX1 or SYT-SSX2 gene fusion. Because this is the primary genetic alteration in these tumors, we sought to identify the impact of molecular heterogeneity of the t(X;18) on cell proliferation, apoptosis, and epithelial differentiation in synovial sarcoma. Seventy-three patients with synovial sarcoma (18 biphasic, 55 monophasic) were selected on the basis of availability of tumor material for molecular and immunohistochemical analysis. Tumors were classified as biphasic on the basis of morphologic glandular differentiation. SYT-SSX fusion transcripts were examined by reverse transcriptase polymerase chain reaction using tumor RNA extracted from frozen or paraffin-embedded tissue. Cell proliferation was assessed immunohistochemically by the Ki-67 labeling index. Apoptosis was analyzed immunohistochemically with BAX and BCL2 antibodies and by the TUNEL method. Immunohistochemical evidence of epithelial differentiation was assessed using antibodies to cytokeratins and epithelial membrane antigen. Approximately two thirds of the tumors had an SYT-SSX1 and one third had an SYT-SSX2 fusion transcript. There was a strong association between SYT-SSX fusion type and histologic subtype. All biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology. There was, however, no association between SYT-SSX fusion type and expression of cytokeratins and epithelial membrane antigen among monophasic tumors. Tumors with SYT-SSX2 had a significantly higher mean and median Ki-67 labeling index than those with SYT-SSX1, but a comparison of Ki-67 according to fusion type, histologic type, and sample source suggested that the main determinants of proliferation rate were the latter two factors. Specifically, monophasic tumors and metastatic tumors showed significantly higher Ki-67 scores. Apoptosis (by TUNEL) was rarely observed, consistent with prominent expression of the anti-apoptotic protein BCL2 in almost all cases. TUNEL, BCL2, and BAX results did not correlate with SYT-SSX fusion type. These data confirm the strong association of SYT-SSX fusion transcript type with morphologic but not immunophenotypic epithelial differentiation in synovial sarcoma.

Apoptosis↗