2-5A antisense telomerase RNA therapy for intracranial malignant gliomas.

Malignant gliomas are the most common intracranial tumors and are considered incurable. Therefore, exploration of novel therapeutic modalities is essential. Telomerase is a ribonucleoprotein enzyme that is detected in the vast majority of malignant gliomas but not in normal brain tissues.

PSK and OK-432-induced immunomodulation of inducible nitric oxide (NO) synthase gene expression in mouse peritoneal polymorphonuclear leukocytes and NO-mediated cytotoxicity.

We investigated whether PSK (a polysaccharide from the mycelia of Coriolus versicolor) or OK-432 (a streptococcal preparation) can up-regulate inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production in mouse peritoneal polymorphonuclear leukocytes (PMNs). Six hrs after intraperitoneal injection of mice with PSK (2,500 microg/mouse) or OK-432 (100 microg/mouse), mouse peritoneal PMNs were restimulated with PSK (500 microg/ml) or OK-432 (10 microg/ml) plus 100 U/ml of mouse interferon-gamma (IFN-gamma) in vitro. Northern blot analysis showed strong synergism between both PSK and OK-432 and IFN-gamma for the induction of iNOS gene expression.

Activins and their receptors in female reproduction.

Activins are growth and differentiation factors belonging to the transforming growth factor-beta superfamily. They are dimeric proteins consisting of two inhibin beta subunits. The structure of activins is highly conserved during vertebrate evolution.

Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension.

Background And Purpose: Although aging and hypertension may predispose hypertensive elderly subjects to cerebral hypoperfusion during orthostatic stress, their effects on the acute cerebral autoregulatory response to hypotension are not known.

Methods: Continuous middle cerebral artery blood flow velocity (BFV) (transcranial Doppler ultrasound) and mean arterial pressure (MAP, Finapres) were measured in response to (1) acute hypotension during standing, (2) steady-state sitting and standing, and (3) hypercarbia during CO(2) rebreathing in 10 healthy young subjects (age 24+/-1 years), 10 healthy elderly subjects (age 72+/-3 years), and 10 previously treated hypertensive elderly (age 72+/-2 years) subjects. CO(2) reactivity was computed as the slope of cerebrovascular conductance (CVC=BFV/MAP) versus end-expiratory CO(2).

Reduced ventricular response irregularity is associated with increased mortality in patients with chronic atrial fibrillation.

BACKGROUND-Variations in the ventricular response interval (VRI) during atrial fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The properties of VRI dynamics associated with prognosis remain undetermined. METHODS AND RESULTS-In 107 patients with chronic AF (age, 64+/-9 years), we analyzed a 24-hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD of 5-minute averages) and VRI irregularity (Shannon entropy of histogram, symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute fluctuations [ApEn(b-b) and ApEn(m-m)]).

Activin, inhibin, and follistatin in zebrafish ovary: expression and role in oocyte maturation.

Activins, inhibins, and follistatins are important regulators of mammalian reproduction. However, their roles in lower vertebrates are poorly understood. In this study, we examined the expression of activin A, inhibin A, and follistatins in the zebrafish ovary and determined their role in final oocyte maturation.

[Changes in the shape of choanal openings and airflow rates during development].

The shape of the choanal openings were examined in 173 babies aged zero to six months using digital video fiberscope inserted via nose. A numerical analysis and the fluid mechanics were then calculated for each recorded choanal opening. The choanal openings in one month old babies were a flat oval shape.

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.

Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts induction of rat adjuvant-induced arthritis.

The effects of cyclooxygenase (COX)-2 antisense oligodeoxynucleotide (ODN) in induction of adjuvant-induced arthritis were investigated. Female Lewis rats were injected with Mycobacterium butyricum intradermally at the base of tails to induce arthritis. Synthetic 18 mer phosphorothioate ODNs corresponding to the translation initiation site of rat COX-2 mRNA were prepared.

Infiltration of tumors by systemically transferred tumor-reactive T lymphocytes is required for antitumor efficacy.

The systemic transfer of ex vivo-activated tumor-sensitized T lymphocytes can mediate immunologically specific regression of established tumors. However, it has not been conclusively established whether the infiltration of systemically transferred T cells into metastases is required for their effector function. In this study, T cells from lymph nodes draining the murine fibrosarcoma MCA 205 cells were activated ex vivo with anti-CD3 monoclonal antibody and interleukin-2.

Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes.

Stickler and Marshall syndromes are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities or different manifestations of a single syndrome. Several mutations causing Stickler syndrome have been found in the COL2A1 gene, and one mutation causing Stickler syndrome and one causing Marshall syndrome have been detected in the COL11A1 gene.

[Emergency coronary artery bypass grafting for ischemic heart disease].

Between June, 1988 and May 1998, 524 patients underwent isolated coronary artery bypass grafting (CABG) utilizing cardiopulmonary bypass in our institution. The 74 patients who underwent CABG on emergency surgery were subjected in this study. Age was ranged 33 to 89 years (mean 65 +/- 1.

Isolation, characterization and mutation analysis of PEX13-defective Chinese hamster ovary cell mutants.

We isolated peroxisome biogenesis mutants ZP128 and ZP150 from rat PEX2 -transformed Chinese hamster ovary (CHO) cells, by the 9-(1'-pyrene)nonanol/ultraviolet method. The mutants lacked morphologically recognizable peroxisomes and showed a typical peroxisome assembly-defective phenotype such as a high sensitivity to 12-(1'-pyrene)dodecanoic acid/UV treatment. By means of PEX cDNA transfection and cell fusion, ZP128 and ZP150 were found to belong to a recently identified complementation group H.

DNA mismatch repair deficiency in curatively resected sextuple primary cancers in different organs: a molecular case report.

A male patient synchronously or metachronously underwent six curative resections after diagnoses of cancers in the rectum, urinary bladder, stomach, colon, liver and lung. Five cancers, excluding early colon cancer, were analyzed for instability in seven microsatellite markers and in transforming growth factor beta type II receptor, insulin-like growth factor II receptor and BAX. All analyzed cancers had replication errors and instability in at least one target gene.

Inhibition of the acid lipase activity by apolipoprotein A-I in the presence of lysosomal proteases.

It was found that the inhibition of the lysosomal acid lipase activity by rat apolipoprotein A-I (apo A-I) was increased with the degradation of apo A-I by the lysosomal proteases. We demonstrated that apo A-I could effectively inhibit the acid lipase activity even in the presence of the lysosomal proteases using the hepatic lysosomal fraction.

TAK-778, a novel synthetic 3-benzothiepin derivative, promotes chondrogenesis in vitro and in vivo.

TAK-778, a novel synthetic 3-benzothiepin derivative, stimulates the formation of cartilaginous nodules in mouse chondroprogenitor-like ATDC5 cells in vitro in association with upregulation of the gene expression of transforming growth factor-beta(2), but not bone morphogenetic protein-4 and insulin-like growth factor-I. One-shot injection of the TAK-778-containing sustained-release microcapsules accelerated the repair process of the full thickness defects of articular cartilage in rabbit knees. Our in vitro and in vivo results indicate that TAK-778 may be a therapeutically useful synthetic agent for articular cartilage repair.

Prognostic value of heart rate variability during long-term follow-up in chronic haemodialysis patients with end-stage renal disease.

Background: Mortality is high in chronic haemodialysis patients with cardiovascular disease, and many of them die suddenly. Reduced heart rate variability (HRV) is an increased risk for death in various populations, but its prognostic value in haemodialysis patients remains uninvestigated.

Methods: We analysed the associations between 24-h HRV measures and long-term mortality through a prospective follow-up of 31 chronic haemodialysis patients who underwent diagnostic coronary angiography.

Aging and spectral characteristics of the nonharmonic component of 24-h heart rate variability.

To examine whether heart rate variability (HRV) during daily life shows power law behavior independently of age and interindividual difference in the total power, log-log scaled coarse-graining spectra of the nonharmonic component of 24-h HRV were studied in 62 healthy men (age 21-79 yr). The spectra declined with increasing frequency in all subjects, but they appeared as broken lines slightly bending downward, particularly in young subjects with a large total power. Regression of the spectrum by a broken line with a single break point revealed that the spectral exponent (beta) was greater in the region below than above the break point (1.

Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders.

Peroxisome biogenesis disorders, including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease, are lethal hereditary diseases caused by abnormalities in peroxisomal assembly. To date, 12 genotypes have been identified. We now have evidence that the complete human cDNA encoding Pex13p, an SH3 protein of a docking factor for the peroxisome targeting signal 1 receptor (Pex5p), rescues peroxisomal matrix protein import and its assembly in fibroblasts from PBD patients of complementation group H.

Late development of an aneurysm of a saphenous vein used as an aortocoronary conduit.

A case of a large saphenous vein aortocoronary aneurysm that developed late after coronary artery bypass grafting is presented. This is the first case of a large saphenous vein aortocoronary aneurysm identified by serial angiography and 3-dimensional computed tomographic scanning.

Effects of complement suppression on xenograft survival in hyperacute rejection.

To examine the significance of complement in discordant cardiac xenograft rejection, morphological changes in the rejection reaction were investigated following administration of FUT-175 (FUT), an anticomplement reagent. Guinea pigs were the cardiac donors, and Wistar rats were the recipients. Four groups of rats were constituted as follows: Group 0 was the control group.

The peroxin Pex14p. cDNA cloning by functional complementation on a Chinese hamster ovary cell mutant, characterization, and functional analysis.

Rat cDNA encoding a 376-amino acid peroxin was isolated by functional complementation of a peroxisome-deficient Chinese hamster ovary cell mutant, ZP110, of complementation group 14 (CG14). The primary sequence showed 28 and 24% amino acid identity with the yeast Pex14p from Hansenula polymorpha and Saccharomyces cerevisiae, respectively; therefore, we termed this cDNA rat PEX14 (RnPEX14). Human and Chinese hamster Pex14p showed 96 and 94% identity to rat Pex14p, except that both Pex14p comprised 377 amino acids.

Critical role of CD11a (LFA-1) in therapeutic efficacy of systemically transferred antitumor effector T cells.

The systemic adoptive transfer of activated T cells, derived from tumor-draining lymph nodes (LNs), mediates the regression of established tumors. In this study, the requirement of cell adhesion molecules, CD11a/CD18 (LFA-1), CD54 (ICAM-1), CD49d/CD29 (VLA-4), and CD106 (VCAM-1), for T cell infiltration into tumors and antitumor function was investigated. Administration of anti-CD11a mAb completely abrogated the efficacy of adoptive immunotherapy for both intracranial and pulmonary metastatic MCA 205 fibrosarcomas.