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Junko Murakami

Publications and source records attributed to Junko Murakami.

9 recordsLinked to original sources
PubMed2005

Down-regulation of p53 by double-stranded RNA modulates the antiviral response.

p53 has been well characterized as a tumor suppressor gene, but its role in antiviral defense remains unclear. A recent report has demonstrated that p53 can be induced by interferons and is activated after vesicular stomatitis virus (VSV) infection. We observed that different nononcogenic viruses, including encephalomyocarditis virus (EMCV) and human parainfluenza virus type 3 (HPIV3), induced down-regulation of p53 in infected cells. Double-stranded RNA (dsRNA) and a mutant vaccinia virus lacking the dsRNA binding protein E3L can also induce this effect, indicating that dsRNA formed during viral infection is likely the trigger for down-regulation of p53. The mechanism of down-regulation of p53 by dsRNA relies on translation inhibition mediated by the PKR and RNase L pathways. In the absence of p53, the replication of both EMCV and HPIV3 was retarded, whereas, conversely, VSV replication was enhanced. Cell cycle analysis indicated that wild-type (WT) but not p53 knockout (KO) fibroblasts undergo an early-G(1) arrest following dsRNA treatment. Moreover, in WT cells the onset of dsRNA-induced apoptosis begins after p53 levels are down-regulated, whereas p53 KO cells, which lack the early-G(1) arrest, rapidly undergo apoptosis. Hence, our data suggest that the down-regulation of p53 facilitates apoptosis, thereby limiting viral replication.

Animals↗
PubMed2003

Effects of RNase L mutations associated with prostate cancer on apoptosis induced by 2',5'-oligoadenylates.

The RNASEL gene, a strong candidate for the hereditary prostate cancer 1 allele (HPC1), encodes a single-stranded specific endoribonuclease involved in the antiviral actions of IFNs. RNase L is activated enzymatically after binding to unusual 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A). Biostable phosphorothioate analogues of 2-5A were synthesized chemically and used to study the effects of naturally occurring mutations and polymorphisms in RNASEL. The 2-5A analogues induced RNase L activity and caused apoptosis in cultures of late-stage, metastatic human prostate cancer cell lines DU145, PC3, and LNCaP. However, DU145 and PC3 cells were more sensitive to 2-5A than LNCaP cells, which are heterozygous for an inactivating deletion mutation in RNase L. The RNase activities of missense variants of human RNase L were compared after expression in a mouse RNase L(-/-) cell line. Several variants (G59S, I97L, I220V, G296V, S322F, Y529C, and D541E) produced similar levels of RNase L activity as wild-type enzyme. In contrast, the R462Q variant, previously implicated in up to 13% of unselected prostate cancer cases, bound 2-5A at wild-type levels but had a 3-fold decrease in RNase activity. The deficiency in RNase L(R462Q) activity was correlated with a reduction in its ability to dimerize into a catalytically active form. Furthermore, RNase L(R462Q) was deficient in causing apoptosis in response to 2-5A consistent with its possible role in prostate cancer development. Our findings support the notion that RNASEL mutations and some variants allow tumor cells to escape a potent apoptotic pathway.

Adenine Nucleotides↗
PubMed2003

Treatment with rokitamycin suppresses the lethality in a murine model of Escherichia coli O157:H7 infection.

The effects of rokitamycin (ROK) and levofloxacin (LEVX) were investigated in a murine model of enterohaemorrhagic Escherichia coli (EHEC) infection. After C3H/HeN mice were inoculated intragastrically with E. coli O157:H7, ROK (20mg/kg) or LEVX (1.2 mg/kg) was administered intragastrically. The death rate of the mice was noted and the faeces were collected to determine viable cell counts of EHEC and for Shiga-like toxins (SLTs) assays. After the mice were sacrificed, the kidneys and colons of some of the mice were removed for histopathological examination. The death rate of mice administered ROK (19%) was significantly lower than that of the control and LEVX-treated groups (80, 93%, respectively). Viable cell counts of EHEC in the faeces of the control and ROK-treated groups were 10(7) and 10(6) CFU/g at day 5 after the infection, respectively. LEVX reduced the bacterial count by less than 100 CFU/g at day 5. The level of SLTs in the faeces from the ROK group were lower than the LEVX-treated and control groups at day 5. The histopathological findings in the kidneys treated with LEVX showed necrotic tubular epithelial cells and those in the colon, inflammatory infiltrates. These were not seen in the ROK-treated group. These results suggested that ROK suppressed release of SLTs from the EHEC and could be useful in the treatment of EHEC infection.

Animals↗
PubMed2003

[Present state of transfusion errors].

Most serious transfusion error is ABO-incompatible transfusion. The Japanese Society of Blood Transfusion reported the results of the National Survey on the present state of ABO-incompatible blood transfusion in Japan. The targets of the survey were 777 hospitals with more than 300 beds, which have transfused more than 3,000 units of blood products per year. The answer could be obtained from 578(74%) hospitals among them. The questionnaire focused on the presence or absence of ABO-mismatched transfusion between January 1995 and December 1999. 115 hospitals(20%) have experienced ABO-mismatched transfusion in the period of the study. The frequency of ABO-mismatched transfusion increased with increasing the number of beds and the units of transfused blood. The ABO-mismatched transfusions were due to clerical or technical errors. The main causes of errors were misidentification of blood bags(42.8%), incorrect blood typing(15.1%) and failure to identify patient (11.5%). Incorrect blood typing errors were performed in 25 cases, and were caused by doctors in 17 cases, others by laboratory technicians. Majority of incorrect blood typing occurred during holidays or night shifts, and in emergency.

ABO Blood-Group System↗
PubMed2003

[Laboratory medicine in the compulsory postgraduate clinical training system--newly revised program in Nihon University School of Medicine].

In 1999, the 4th report of the discussion group on 21st century medicine and health care proposed that it was necessary to establish in medical education a core curriculum emphasizing carefully selected basic content and to greatly expand the number of subjects that students might take electively. Following this report, a model core curriculum was made by the research and development project committee for medical educational programs in 2001. Similarly, the necessity of establishing a standardized postgraduate training curriculum and system has been discussed for many years. The Departments of Education and Technology and Welfare and Labor proposed a new curriculum named "Objectives in postgraduate clinical training" in order to ensure the quality of the medical doctors licensed to practice medicine in postgraduate clinical training in 2002. Following this new curriculum, Nihon University School of Medicine revised and enlarged its postgraduate program. All graduates are required to enter a full rotation program including general disciplines for two years. In addition to this basic curriculum, an elective curriculum will be added, providing attractive training programs based on medical trainees' needs. The training program in Laboratory Medicine is administered in the 2nd year as an elective program.

Curriculum↗
PubMed2002

[Acute renal failure in an infant attributable to arterial cannula malposition during cardiopulmonary bypass via ministernotomy].

A 6-month-old female (4.9 kg) with multiple congenital heart lesions underwent intracardiac repair with the aid of cardiopulmonary bypass (CPB) through a lower half sternotomy. Aortic cannulation, venous cannulation, and cardioplegia cannula insertion were all accomplished through the ministernotomy. During the CPB, in spite of a high perfusion flow rate (182 ml.kg-1.min-1), the systemic arterial pressure was persistently low (mean values = 25-35 mmHg) and the urine output was greatly reduced (< 1 ml.hr-1). In addition, inappropriate increases in the arterial inflow line pressure were recognized. Since abutment of the cannula tip against the aortic intima was suspected, several attempts were made to correct its malpositioning. During the CPB, hemolysis was also found in the mixed venous blood. Since the oliguria and resultant hyperkalemia persisted after weaning from the CPB, peritoneal dialysis was introduced immediately after the surgery. Her renal function gradually recovered postoperatively, and she was finally weaned from the peritoneal dialysis on the 13th postoperative day. Although the ministernotomy has been proposed to be a safe approach for most of cardiac surgeries, it appears to increase the risk for arterial cannula malposition as compared to the standard full-length sternotomy in small pediatric patients.

Acute Kidney Injury↗
PubMedDate not supplied

Endometrial cytodiagnosis using a new softcyte versus a conventional endocyte.

A new endometrial cytologic sampling device, softcyte, was used in cytological screening for endometrial cancer, and was compared with the endocyte with regard to manipulability, adverse effects (including pain and hemorrhage), and cellular findings (including the quantity of cells collected, the success rate, cell freshness, and cellular clumping). A total of 315 women (premenopause 251, postmenopause 64) were randomly assigned to two groups who underwent the endometrial cytological screening with either the softcyte or the endocyte. To assess the value of the softcyte we compared it with the endocyte. Endometrial cytology using a softcyte or an endocyte achieved high correct diagnosis rate for cancer, and both instruments are valuable as endometrial cytologic sample devices. The softcyte causes only mild pain on introduction and during collection, and a large quantity of cells could be harvested. These results suggest that the softcyte is a useful cytologic sampling device in screening for endometrial cancer.

Adult↗