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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 217 records · Page 12Linked to original sources

High telomerase activity is an independent prognostic indicator of poor outcome in colorectal cancer.

Telomerase activity and altered telomere length have been extensively studied in many kinds of malignant tumors for clinical diagnostic and/or prognostic utilities. In the present study, we investigated telomerase activity and telomere length in colorectal cancers and noncancerous colonic mucosa specimens in 100 patients between 1991 and 1996. To determine whether the level of telomerase activity or telomere length is a prognostic indicator of patient outcome, we followed these patients more than 3 years after surgery. Among 100 primary colorectal cancer specimens, 96 specimens had telomerase activity. Because noncancerous mucosa has some detectable telomerase activity, we divided the levels of telomerase activity into three categories: high (>50-fold more than that in noncancerous mucosa); moderate (10- to 50-fold); and low (<10-fold) levels. Among 100 cancer tissues, 28 showed moderate telomerase activity and 44 showed high telomerase activity. The frequency of tumors with moderate or high telomerase activity showed no significant relationship with any clinicopathological factors. The prognosis of the patients with high telomerase activity was significantly worse than that for patients with moderate and low telomerase activity (P < 0.01). Among the 87 patients with curative surgery, disease-free survival rate of those with high telomerase activity was also significantly poorer (P < 0.01). These results indicate that a high level of telomerase activity may be an independent prognosis-predicting factor in the patients with colorectal cancer.

Adult↗

[Five cases of surgically resected chronic expanding hematoma in the chest].

We report surgically treated 5 cases of chronic expanding hematoma in the chest. Three were male and two were female, aged 53 to 76. All patients except one who was thought to have an early stage of chronic expanding hematoma, had severe dyspnea due to compression of lung parenchyma or heart. Complete removal of the hematoma with fibrous capsule was done in two cases, but in three cases the hematoma was removed but the capsule was not because of severe adhesion to the surrounding structures. Post operative course was different to each other. One patient whose capsule was not removed completely have recurrent hematoma in the chest. The pulmonary or cardiac function were improved greatly except for the two cases; an early stage case and a recurrent case. We conclude that surgical removal is the first treatment for chronic expanding hematoma and complete removal of it with capsule is recommended.

Aged↗

Right ventricular aneurysm caused by acute myocarditis.

The first case of right ventricular aneurysm caused by acute myocarditis is reported. Positive gallium-67 uptake and contrast enhancement in the gadolinium diethylenetriaminepentaacetic acid-enhanced magnetic resonance images were detected in the apical region surrounding the aneurysm, suggesting transmural myocardial inflammations in the apical portion of the heart. The aneurysm was repaired surgically, and biopsy of the right ventricular myocardium showed replacement fibrosis and inflammatory infiltrate.

Acute Disease↗

[Validity and controversies in the new postoperative pathologic TNM classification based on the results of surgical treatment of non-small cell lung cancer].

In 1997, the latest revision of the International System for Staging Lung Cancer was published. To validate the new pathologic TNM classification for non-small cell lung cancer (NSCLC), we analyzed the survival data of 455 patients who underwent pulmonary resection and pathologic staging at our institution from January 1980 through December 1999. The overall 5-year survival rate was 51.0%. Using the revised new stage classification, the survival rate for each stage was as follows; IA: 74.2%, IB: 66.4%, IIA: 56.0%, IIB: 51.8%, IIIA: 21.0%, IIIB: 16.0%, and IV: 0%. The current TNM classification well reflected the long-term prognostic hierarchy. There were significant differences in survival rates between patients with stage IA and IB, and between patients with stage IIB and IIIA. However, there was no significant difference between patients with stage IIA and IIB. No significant difference in survival was observed among patients with stage IIIA, stage IIIB, and stage IV. Five-year survival rate of 48.3% in the T3N0M0 category was significantly better than that of 21.0% found in the new stage IIIA. The survival of patients with intrapulmonary metastases in the same lobe (pm1) was not significantly better than that found in the stage IV. The TNM staging system accurately reflects the prognosis in NSCLC, but some stage definitions can be discussed.

Adolescent↗

[Temporal and geographical variation in epidemics determined from the results of an infectious disease surveillance system in Japan description of epidemic patterns by data-based criteria for epidemic periods].

OBJECTIVE: After developing criteria for epidemic periods for 16 infectious diseases, we investigated temporal (annual and monthly) and geographical (regional) variation in epidemics. METHODS: Data from an infectious disease surveillance system for the years 1993 to 1997 were used for the analysis. The weekly number of patients per monitoring station was calculated from the data and used in developing criteria for an epidemic period. Based on these latter, we calculated the average number of epidemics occurring at each public health center in a year, an average length of the epidemic period, and the average number of patients per monitoring station reported during an epidemic period. These figures were used to explore temporal (annual, monthly) and geographical (regional) variation. RESULTS: With most diseases, the average number of epidemics occurring at a public health center was 0.3-0.5 per year and the average length of an epidemic period was 6-12 weeks. The average number of patients per monitoring station reported during an epidemic period differed according to the diseases. These indices showed that there were few annual differences, but great monthly differences, in most diseases. The average number of epidemics occurring in a public health center showed regional differences with some diseases. CONCLUSION: Temporal and geographical variation in epidemics for 16 infectious diseases was established by developing criteria for an epidemic period.

Data Collection↗

[Anesthetic management of MICS with Port-Access system].

Port-Access system (P-A) is a catheter-based system for minimally invasive cardiac surgery (MICS) characterized by avoidance of full sternotomy with the aid of Endoaortic Clamp Catheter (EAC) for intra-aortic occlusion instead of the conventional external aortic crossclamping. In our hospital, eleven patients underwent MICS using P-A from August in 1998 to the present time. We compared the intra- and post-operative anesthetic management of these patients with that of fifteen patients done by using our conventional MICS method, Saitama Medical School system (SMS). Anesthetic management of these MICS patients is directed toward early extubation, and therefore all patients receive intravenous anesthesia with a small dose of fentanyl combined with inhalational agent or propofol. Without increasing the time of the cardiopulmonary bypass (CPB) and the amount of the intraoperative bleeding, MICS with P-A needs more time to begin CPB than that with SMS because it takes more time to insert these catheters, especially EAC into the suitable position using transesophageal echocardiography (TEE) and fluoroscopy. The time to start CPB must be shortened by skilled cannulation. There is no difference in the postoperative length of ICU and hospital stays between P-A and SMS. In MICS, TEE is the window to the heart for both surgeon and anesthesiologist and used to guide for the placing of the catheters and weaning from CPB, and anesthesiologist should be skillful in using TEE to evaluate the de-airing procedure and assess volume load and contractility of the left ventricle.

Adult↗

Beneficial effect of combination therapy with ozagrel and pranlukast in exercise-induced asthma demonstrated by krypton-81 m ventilation scintigraphy--a case report.

INTRODUCTION: We evaluated the effect of combination therapy with thromboxane A2 synthesis inhibitor and leukotriene receptor antagonist in a patient with exercise-induced asthma using krypton-81 m ventilation scintigraphy. CLINICAL PICTURE: In a patient with exercise-induced asthma, we found exercise-induced abnormalities of respiratory function test and ventilation scintigraphy, and increases in plasma concentrations of thromboxane B2 and leukotriene C4 with exercise. TREATMENT: A thromboxane A2 synthesis inhibitor (ozagrel) and a leukotriene receptor antagonist (pranlukast) were prescribed. OUTCOME: After treatment for 2 weeks, abnormalities of respiratory function test and ventilation scintigraphy improved. CONCLUSIONS: The combination therapy with ozagrel and pranlukast might be useful for the relief of symptoms in patients with exercise-induced asthma, and krypton-81 m ventilation scintigraphy could be a useful tool for visible evaluation of treatment.

Asthma, Exercise-Induced↗

A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2.

Human chromosome 11q23.2 has been proposed to contain a tumor suppressor gene(s) whose deletion has been associated with cancer of the lung and breast and with neuroblastoma. To analyze the genomic structure and to isolate a candidate tumor suppressor gene from this region, we constructed a 2-Mb sequence-ready contig map using bacteriophage P1 (P1), bacterial artificial chromosome (BAC), and P1-derived artificial chromosome (PAC). The map comprises a contig of 24 overlapping P1, BAC, and PAC clones. To isolate gene fragments from the region, we performed direct cDNA library screening, exon trapping, EST mapping, and genomic sequencing using the P1, BAC, and PAC clones. Sequence analysis of 5 clones, which spans 23% (458,738 bp) of the region, and extensive gene scanning along the entire region revealed that the region is extraordinarily scarce in genes, but we identified one ubiquitously expressed novel gene and one testis-specific gene fragment. The novel gene, which we call IGSF4 (immunoglobulin superfamily 4), is transcribed into a 1.6- or 4.4-kb RNA encoding a 442-amino-acid protein. It shares strong homology with mouse IGSF-B12 and cell adhesion molecules NCAM1 and NCAM2 within their Ig-like C2-type domains. The IGSF4 gene, a novel gene that is shown to be located in the common loss of heterozygosity region, possesses a number of interesting features and may be good candidate for a tumor suppressor gene.

Amino Acid Sequence↗

Transcription factors in DNA replication.

Accumulating evidence suggests the involvement of transcription factors in the regulation of DNA replication in eukaryotic cells. Almost all eukaryotic DNA viruses contain binding sites for transcription factors which function as auxiliary elements for DNA replication initiation at replication origins, and, indeed, the binding of transcription factors to these elements has been shown to stimulate DNA replication. Transcription factors also regulate some of the chromosome DNA replication origins of budding yeast, indicating that transcription factor involvement in DNA replication is not restricted to viruses. Consistent with this notion, recently determined replication origins of higher eukaryotes have been found occasionally to associate with transcription factor binding sites, although there is no direct evidence for the involvement of the factors that bind to these sequences in DNA replication. Analyses using viral and yeast systems have suggested that transcription factors stimulate the formation of the replication initiation complex by engaging in specific interactions with proteins of the initiation complex and/or by modulating the repressive chromatin structure around origins of replication. These mechanisms are analogous to those advanced to explain stimulation of transcription by transcription factors. The accumulated data suggests that transcription factors play a general role in the formation of functional complexes on chromosomes.

Animals↗

Dietary induction of ornithine decarboxylase in male mouse kidney.

In male mouse kidney, ornithine decarboxylase (ODC) is induced after feeding, and the induction depends on dietary protein content. 24 h after feeding with 50% casein-containing meal, ODC activity and amount of immunoreactive ODC protein increased more than 10-fold, ODC mRNA level increased 2-fold, and the ODC half-life extended 7-fold. The renal ODC induction after feeding is, therefore, due mainly to stabilization of ODC protein. Urinary excretion of putrescine increased in response to the ODC induction, but the renal polyamine contents scarcely changed. Consistently, the level of antizyme, a polyamine-inducible protein, determined as the ODC-antizyme complex level, scarcely changed after feeding, and the antizyme/ODC ratio in the kidney largely decreased, resulting in the stabilization of ODC protein. The present results suggest that the strong excretion system of the kidney for newly synthesized polyamines enables renal ODC escape from antizyme-mediated feedback regulation.

Animals↗

Lack of CD44 variant 6 expression in advanced extrahepatic bile duct/ampullary carcinoma.

BACKGROUND: Transmembrane proteins of the CD44 family play roles in cell-cell and cell-matrix interactions, and their aberrant expression has been reported to be associated with the growth and metastasis of various tumors. The authors examined CD44 standard (CD44st) and CD44 variant 6 (CD44v6) expression in extrahepatic bile duct (EHBD)/ampullary carcinoma. METHODS: In 36 EHBD/ampullary carcinomas, immunohistochemical analyses with monoclonal antibodies against the human CD44st protein or CD44v6 protein were performed by the streptavidin-biotin immunoperoxidase method. The relation between expression of the proteins and lymph node metastases or patient outcome was investigated. To verify the lack of CD44v6 mRNA expression in tumors negative for CD44v6 staining, reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot hybridization were performed. RESULTS: Immunohistochemical analyses revealed that 13 of 36 carcinomas (36.1%) expressed the CD44v6 protein. Only 2 of 13 CD44v6-expressing primary tumors (15.4%) had regional lymph node metastases, whereas 14 of 23 tumors showing no CD44v6 expression (60.9%) had lymph node metastases (Fisher exact test, P<0.01). Moreover, a lack of CD44v6 expression was correlated significantly with poor prognosis (generalized Wilcoxon test, P<0.05). Eleven of 13 CD44v6 positive tumors showed CD44st expression, which also was correlated with prognosis. RT-PCR and Southern blot hybridization revealed a lack of CD44v6 mRNA expression in the tumors that were negative for CD44v6 staining. CONCLUSIONS: The results of the current study suggest that a lack of expression of CD44, especially CD44v6, is correlated with lymph node metastases and poor prognosis, and may be a prognostic factor for patients with EHBD/ampullary carcinoma.

Adult↗

Different roles of glycosylphosphatidylinositol in various hematopoietic cells as revealed by a mouse model of paroxysmal nocturnal hemoglobinuria.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have one or a few clones of mutant hematopoietic stem cells defective in glycosylphosphatidylinositol (GPI) synthesis as a result of somatic mutation in the X-linked gene PIG-A. The mutant stem cell clone dominates hematopoiesis by a mechanism that is unclear. To test whether a lack of multiple GPI-anchored proteins results in dysregulation and expansion of stem cells, we generated mice in which GPI-anchor negative cells are present only in the hematopoietic system. We transplanted lethally irradiated mice with female fetal liver cells bearing one allele of the Piga gene disrupted by conditional gene targeting. Because of the X-chromosome inactivation, a significant fraction of the hematopoietic stem cells in fetal livers was GPI-anchor negative. In the transplanted mice, cells of all hematopoietic lineages contained GPI-anchor negative cells. The percentage of GPI-anchor negative cells was much higher in T lymphocytes including immature thymocytes than in other cell types, suggesting a regulatory role for GPI-anchored proteins at an early stage of T-lymphocyte development. However, the proportions of GPI-anchor negative cells in various blood cell lineages were stable over a period of 42 weeks, indicating that Piga mutation alone does not account for the dominance of the mutant stem cells and that other phenotypic changes are involved in pathogenesis of PNH.

Animals↗

Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors.

Class 1 and 3 semaphorins repulse axons but bind to different cell surface proteins. We find that the two known semaphorin-binding proteins, plexin 1 (Plex 1) and neuropilin-1 (NP-1), form a stable complex. Plex 1 alone does not bind semaphorin-3A (Sema3A), but the NP-1/Plex 1 complex has a higher affinity for Sema3A than does NP-1 alone. While Sema3A binding to NP-1 does not alter nonneuronal cell morphology, Sema3A interaction with NP-1/Plex 1 complexes induces adherent cells to round up. Expression of a dominant-negative Plex 1 in sensory neurons blocks Sema3A-induced growth cone collapse. Sema3A treatment leads to the redistribution of growth cone NP-1 and plexin into clusters. Thus, physiologic Sema3A receptors consist of NP-1/plexin complexes.

Animals↗

1,3-Disubstituted benzazepines as novel, potent, selective neuropeptide Y Y1 receptor antagonists.

A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R(1) and R(3) substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K(i) values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R(1) and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R(3) in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido++ +))benzyl )-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [(125)I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K(i) = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca(2+) concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.

Animals↗

Block of granulocytic differentiation of 32Dcl3 cells by AML1/ETO(MTG8) but not by highly expressed Bcl-2.

The chimeric gene, AML1/ETO (MTG8), generated in t(8;21) acute myeloid leukemia enhances the expression of Bcl-2. To evaluate whether this enhancement is the primary role of AML1/ETO in leukemogenesis, effects of over-expression of Bcl-2 in the murine myeloid precursor cell line, 32Dcl3, were examined. When 32Dcl3 cells expressing exogenous Bcl-2 were induced to differentiate, the onset of morphological differentiation was delayed. However, even the cells expressing very high levels of exogenous Bcl-2 eventually underwent differentiation without a significant decrease in the synthesis of Bcl-2. On the contrary, 32Dcl3 cells stably expressing AML1/ETO were completely resistant to differentiation and continued to grow in the presence of G-CSF. These results are consistent with the interpretation that stimulation of Bcl-2 expression is not the primary target of AML1/ETO.

Animals↗

Control of complement activities for immunoisolation.

Immunoisolation of cells by semipermeable membranes is a most promising approach to transplant xenogeneic cells. Although membranes which allow xenotransplantation have been reported, ambiguity remains as to their long term effectiveness. In this review, we would like to reconsider the immuno-isolative effectiveness of membranes reported from the standpoint of permeability and present our strategy to prepare membranes that can realize long-term functioning of xenograft. There are distinct different types of semi-permeable membranes, hydrogel membranes and ultrafiltration membranes. Studies on their permeability indicated that neither of these membranes effectively fractionate solutes on the basis of molecular size under a diffusion-controlled process, nor thus can they immuno-isolate xenograft for a long time. Humoral immunity including antibodies and complement proteins is suspected of playing a major role in the rejection of xenografts. Control of complement cytolytic activities, not antibody permeation, may be a key factor determining the fate of the xenograft enclosed in membranes. We found that the microbead containing poly(styrene sulfonic acid) can consume complement cytolytic activities and thus can effectively protect xenogeneic islets of Langerhans in diabetic mice from the humoral immunity.

Animals↗