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H Maruta

Publications and source records attributed to H Maruta.

At least 37 records · Page 2Linked to original sources
PubMed1997

Inhibitors of poly(ADP-ribose) polymerase suppress nuclear fragmentation and apoptotic-body formation during apoptosis in HL-60 cells.

The effects of 3-aminobenzamide (3ABm) and benzamide (BAm), known specific inhibitors of poly(ADP-ribose) polymerase (PARP), on actinomycin D (Act D)-induced apoptosis in HL-60 cells were examined. These inhibitors had no appreciable effect on apoptotic DNA fragmentation, chromatin condensation or PARP restriction cleavage, but clearly inhibited morphological changes, especially nuclear fragmentation and apoptotic-body formation, in a dose-dependent manner. These results suggest that the synthesis of ADP-ribose polymers is not essential for the progression of apoptotic DNA fragmentation and chromatin condensation, but is required in the processes leading to nuclear fragmentation and the subsequent apoptotic-body formation during apoptosis in HL-60 cells.

Aminobenzoates↗
PubMed1997

Role of (ADP-ribose)n catabolism in DNA repair.

Poly(ADP-ribose) is a reversible covalent-modifier of chromosomal proteins in eukaryotic cells. The function of poly(ADP-ribose) is not clear, although it has been suggested to be involved in the regulation of DNA transactions such as replication, repair, and transcription. Here we describe a specific competitive inhibitor of poly(ADP-ribose) glycohydrolase, a macrocircular ellagitannin oenothein B, and a nuclear system prepared from synchronized HeLa S3 cells at mid-G1 phase that enable us to examine the role of poly(ADP-ribose) catabolism in DNA repair. The results suggest that poly(ADP-ribose) is capable of generating ATP by the concerted action of poly(ADP-ribose) glycohydrolase and ADP-ribose pyrophosphorylase and that this ATP enables repair DNA synthesis.

Adenosine Triphosphate↗
PubMed1997

The GTPase and Rho GAP domains of p190, a tumor suppressor protein that binds the M(r) 120,000 Ras GAP, independently function as anti-Ras tumor suppressors.

p190 is a Tyr-phosphorylatable G protein of M(r) 190,000 that binds NH2-terminal SH2 domains of GAP1, a Ras GAP of M(r) 120,000. p190 contains at least two functional domains: a GTPase domain at the NH2 terminus and a GAP domain at the COOH terminus that can attenuate signal-transducing activity of three distinct G proteins (Rac, Rho, and CDC42). Here, we demonstrate that overexpression of either an antisense p190 RNA or a dominant negative mutant (Asn36) of p190 GTPase domain (residues 1-251) but not the wild-type p190 GTPase domain is able to transform normal NIH/3T3 fibroblasts. Furthermore, overexpression of either the wild-type p190 GTPase domain or the COOH-terminal GAP domain can suppress v-Ha-Ras-induced malignant transformation. These results indicate that p190 contains at least two distinct anti-Ras tumor suppressor domains, the GTPase and GAP domains, and suggest that one of the mechanisms underlying the suppression of Ras-transformation by p190 is the attenuation by p190 GAP domain of Rac/Rho/CDC42 signalings, which are essential for Ras-transformation. In fact, the p190 GAP domain alone suppresses the expression of the c-Fos gene, which is mediated by Rac/Rho/CDC42 and is required for oncogenicity of Ras.

Animals↗
PubMed1997

Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial thrombotic endocarditis in rats.

High-altitude hypoxia causes polycythaemia and a hypercoagulable state in humans and animals. This study examines the effects of a hypobaric, hypoxic environment (HHE) on the blood coagulation system in rats. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m in altitude for 1-12 weeks. After 2 weeks of exposure to HHE, platelet counts decreased significantly; after 4 weeks, the prothrombin and activated partial thromboplastin times were significantly prolonged, compared with those of control rats. In addition, individual coagulation factors (VII, IX, X, XI, and XII) were significantly decreased at 8 weeks (P < 0.05). Levels of anti-thrombin III and alpha 2-plasmin inhibitor also decreased (between 4 and 8 weeks). After 4-12 weeks of exposure to HHE, 30 of 56 rats (54 per cent) developed (i) non-bacterial thrombotic endocarditis (NBTE) or (ii) infarction of the myocardium or kidney, or both (i) and (ii). The incidence of NBTE increased from 33 per cent (5/15 rats) at 4 weeks to 100 per cent (7/7 rats) at 12 weeks. Electron microscopy showed detached endothelial cells in the mitral valves at 1 week; platelets adhered to the subendocardial matrix and platelet aggregation with thrombus formation was seen at 2 weeks of exposure. The results suggest that exposure to HHE induces a hypercoagulable state and causes an NBTE in rats that may result in consumption coagulopathy.

Altitude Sickness↗
PubMed1997

The restrictive proteolysis of alpha-fodrin to a 120 kDa fragment is not catalyzed by calpains during thymic apoptosis.

The alpha-subunit (240 kDa) of fodrin was found to be digested selectively to a 120 kDa fragment during apoptosis of rat thymocytes in vivo and in vitro. This fragment was detected by an antibody (Ab) against full length alpha-fodrin, but not by the anti-N-terminal sequence (GMMPR) of the mu-calpain-generated 150 kDa fragment Ab or the anti-PEST sequence of alpha-fodrin Ab. On the other hand, basal levels of the 150 kDa fragment were constantly recognized by these three antibodies during apoptosis. The production of the 120 kDa fragment during apoptosis was not affected by the addition of calpain inhibitors such as Ac-LLLnal and E-64d, despite inhibition of the generation of the 150 kDa fragment. When x-irradiated thymocytes were incubated in the presence of N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK), both production of the 120 kDa fragment and apoptosis were suppressed. Purified mu- and m-calpain did not catalyze the formation of the 120 kDa fragment from purified alpha-fodrin in vitro. These results suggest that a protease different from calpains is involved in the major process of alpha-fodrin proteolysis to a 120 kDa fragment during thymic apoptosis.

Journal Article↗
PubMed1997

Influence of blood sample oxygen tension on blood glucose concentration measured using an enzyme-electrode method.

OBJECTIVE: To determine the accuracy of a bedside glucometer with an enzyme-electrode sensor based on enzyme oxidation by glucose oxidase. DESIGN: Prospective, cross-sectional clinical study. SETTING: Operating room in a public hospital. PATIENTS: Fifty-four patients undergoing surgical procedures for a derivation (n = 17) and a validation (n= 37) study. INTERVENTIONS: Arterial blood samples were obtained via a 20-gauge cannula inserted into each patient's radial artery. MEASUREMENTS AND MAIN RESULTS: Glucose measurements and arterial blood gas analyses were concurrently performed, using 48 blood samples for the derivation study and 45 blood samples for the validation study of this technique. Blood glucose concentrations were measured with both a bedside glucometer using an enzyme-electrode method and a laboratory glucometer based on the colorimetric method. The bedside glucometer consistently underestimated the glucose concentrations and the underestimation was related to the sample oxygen tension but not to hematocrit, plasma protein, creatinine, uric acid, or bilirubin. The present investigation used the following correction formula: (corrected glucose value) = (glucose concentration obtained by a bedside glucometer) + 0.1 x (sample oxygen tension) + 16. The corrected data were in agreement with the laboratory-determined glucose values (i.e., the mean difference and precision were 0.4 and 7.1 mg/dL, respectively). A validation study confirmed the generalization of the present correction formula which facilitates a more accurate estimation of blood glucose concentrations. CONCLUSIONS: Blood glucose values measured using a bedside glucometer in this study were influenced by the sample oxygen tension. We used a corrective equation which improved the accuracy of estimating blood glucose values to a clinically acceptable range.

Adult↗
PubMed1997

[NF1 (neurofibromatosis type 1)].

Several distinct Ras GTPase activating proteins (GAPs) from mammals, including Ras GAP of 120 kDa (GAP1) and NF1, stimulate the intrinsic GTPase activity of normal Ras, but not oncogenic Ras mutants (Trahey and McCormick, 1987). That is the reason why normal Ras remains predominantly in the inactive GDP-bound form (D-Ras), whereas oncogenic Ras remains constitutively in the active GTP-bound form (T-Ras). NF1 is a tumor suppressor of 2818 amino acids whose disruption or deletion causes brain tumors called neurofibromatosis type 1 by elevating the T-Ras level. T-Ras activates several distinct oncogenic effectors, including Ser/Thr kinase Raf, GAP1, P1-3 kinase, PKC-zeta and Ra1 GDS. Interestingly, the binding of T-Ras to either GAPs or these oncogenic effectors requires the same effector domain I (residues 32-40) of T-Ras molecule. In other words, these GAPs and effectors compete for binding to T-Ras. Using a series of N- and C-terminal deletion mutants of NF1, we identified a 78 amino acid fragment (NF78, residues 1441-1518) as the minimum GAP domain, and a 56 amino acid fragment (NF 56, residues 1441-1496) as the minimum Ras-binding domain. Furthermore, we identified the Raf fragment of 81 amino acids (Raf81, residues, 51-131) as the minimum Ras-binding domain with a high affinity. We found that (i) these NF1 fragments and Raf81 compete for binding to T-Ras, and that (ii) over-expression of these NF1 or Raf fragments strongly suppresses the malignant transformation caused by oncogenic Ras mutants. Thus, these agents offer a unique opportunity to control the proliferation of T-Ras-associated tumors that represent more than 30% of all human carcinomas including neurofibromatosis type 1.

Animals↗
PubMed1997

[F-actin cappers].

Members of a large protein family that cap the barbed (fast-growing) end of actin filament (F-actin) are called F-actin "Cappers". The first F-actin capper called Cap 28/31 is a heterodimer of 28 kDa and 31 kDa proteins, and was isolated from a soil amoeba called Acanthamoeba (Isenberg et al., 1980). F-actin cappers are present in any eucaryotes from yeast to human, and block actin polymerization by capping the fast-growing end of F-actin. In non-stimulated cells, most of the fast-growing ends of actin filaments are capped by an 1:1 complex of actin monomer (G-actin) and profilin, a PIP2-binding protein. When cells are stimulated by one of the mitogenic cytokines such as EGF and PDGF, Ras is activated, and consequently Rac is activated. Rac in turn activates PI-4 kinase which produces PIP2. PIP2 then binds profilin, and dissociates the profilin/G-actin complex, leading to uncapping of the fast-growing end of actin filament, and induces a rapid actin polymerization. Eventually, this results in the induction of membrane ruffling. We found that (1) the Ras/Rac-induced uncapping is required for oncogenicity of Ras, and (2) either capping at the fast-growing end by F-actin cappers such as tensin and cytochalasins, or sequestering PIP2 by PIP2-binders such as cofilin mutants (blocking the uncapping) is sufficient to suppress the malignant transformation caused by oncogenic Ras mutants such as v-Ha-Ras.

Animals↗
PubMed1996

Inhibitory effect of tannic acid on human immunodeficiency virus promoter activity induced by 12-O-tetra decanoylphorbol-13-acetate in Jurkat T-cells.

We investigated the effect of tannic acid, a potent inhibitor of poly(ADP-ribose) glycohydrolase, on human viral gene transcription, by using chloramphenicol acetyl transferase (CAT) assay experiments transfecting Jurkat cells with CAT reporter constructs that contain the promoter region of human immunodeficiency virus (HIV) or of human T-cell leukemia virus type I (HTLV-1). The activity of HIV promoter induced by treatment with 12-O-tetradecanoylphorbol-13-acetate was suppressed by the addition of tannic acid. On the other hand, HTLV-1 promoter activity induced by the p40(tax) expression plasmid was not affected by tannic acid treatment. Deletion analysis of the HIV promoter revealed that a 30-bp element located immediately upstream of NF-kappa B motifs was responsible for the suppressive effect of tannic acid. This was supported by the observations that the negative effect of tannic acid was introduced to tannic acid-non-responsive thymidine kinase promoter by the insertion of this element 5'-upstream of the promoter.

Base Sequence↗
PubMed1996

The effect of sevoflurane and isoflurane on the neuromuscular block produced by vecuronium continuous infusion.

Volatile anesthetics enhance the action of neuromuscular blockade to various degrees, although the influence of sevoflurane on the neuromuscular block has not yet been characterized. The purpose of this investigation is to determine the vecuronium infusion rate requirement under sevoflurane anesthesia and to compare it to that of isoflurane anesthesia. Twenty patients scheduled for otorhinolaryngologic surgery were randomly assigned to receive either sevoflurane (SEV) or isoflurane (ISO) at 1 minimum alveolar anesthetic concentration (MAC) (1.7% and 1.2%, respectively) in combination with 67% nitrous oxide. Anesthesia was induced with 5 mg/kg thiopental and muscle relaxation was obtained by a bolus of vecuronium infusion to achieve 90% muscle relaxation. The plasma concentrations of vecuronium (CVEC) and 3-desacetylvecuronium (CDES) at steady state were measured with a gas chromatographic assay. There was no difference between SEV and ISO in the following variables: the vecuronium infusion rate requirements to achieve 90% muscle relaxation (0.42 +/- 0.11 [SEV] vs 0.40 +/- 0.10 [ISO] microgram-kg-1.min-1), CVEC (144.4 +/- 38.1 [SEV] vs 149.7 +/- 69.2 [ISO] ng/mL), CDES (57.2 +/- 20.3 [SEV] vs 65.3 +/- 26.1 [ISO], ng/mL), and plasma vecuronium clearance (2.85 +/- 0.86 [SEV] vs 3.19 +/- 1.24 [ISO] mL.kg-1.min-1). This study indicates that SEV at 1 MAC requires a vecuronium infusion rate similar to that of ISO at 1 MAC to achieve 90% muscle relaxation.

Adult↗
PubMed1995

Two regions with differential growth-modulating activity in the N-terminal domain of ras GTPase-activating protein (p120GAP) src homology and Gly-Ala-Pro-rich regions.

Ras GTPase-activating protein of 120 kDa (p120GAP) consists of a hydrophobic Gly-Ala-Pro-rich stretch and src homology 2 and 3 (SH2/SH3) domains in the N-terminal half, and a Ras GTPase-activating domain at the C-terminus. In order to evaluate the potential for cell-growth regulation of the N-terminal region of p120GAP, we isolated three distinct clones of rat 3Y1 fibroblast that express either the SH2/SH3 regions alone, the N-terminal half, or the whole p120GAP. Clones that express the SH2-SH3-SH2 regions of 37 kDa (p37SH2/3) at a level of only 15-30% that of endogenous p120GAP, but not clones expressing complete p120GAP or its N-terminal half of 55 kDa (p55GAP-N), showed significant growth-enhancing properties, including a higher saturation density and increased uptake of 2-deoxyglucose. Clones expressing p37SH2/3 or p55GAP-N maintained high levels of tyrosine-phosphorylated p190 and p62, both of which bind the SH2 domain of p120GAP, while clones expressing the whole p120GAP showed no tyrosine phosphorylation of p62. Furthermore, in the presence of a phorbol ester, only the clones expressing p37SH2/3 showed increased tyrosine phosphorylation of p62 and c-fos expression. These clones also showed the ability of colony formation in soft agar. These results indicate that the N-terminal domain of p120GAP consists of two regions with differential growth-enhancing activities and suggest that the transforming potential of SH2/SH3 regions is blocked by the N-terminal hydrophobic Gly-Ala-Pro stretch.

Amino Acid Sequence↗
PubMed1995

[Testicular findings, endocrine features and therapeutic responses of men with idiopathic hypogonadotropic hypogonadism].

The purpose of this study is to clarify the pathological and endocrinological variations of male idiopathic hypogonadotropic hypogonadism (IHH) from the viewpoint of testicular maturation. Twenty-five patients with IHH were classified into 3 groups according to the degree of germ cell maturation. The most mature germ cells in patients with severe IHH, moderate IHH and mild IHH were spermatogonia, primary spermatocytes and postmeiotic germ cells, respectively. All patients were treated with hCG alone or a combination of hMG-hCG for 1 year or more. The therapeutic efficacy of gonadotropin therapy was evaluated by findings of semen analysis, spermatogenesis and sexual maturation. The total GCI, which was expressed as the number of germ cells per Sertoli cell, diameter of the seminiferous tubules and testicular volume in mild IHH were the largest among the 3 IHH groups, and those in severe IHH were the smallest. Even in mild IHH, spermatogonial proliferation and meiotic activity were quantitatively smaller than those of normal pubertal boys. All patients showed extremely low basal testosterone levels. Response of serum testosterone to hCG administration correlated to the maturity of germ cells. Basal serum gonadotropin levels and responses to GnRH administration varied widely among the 3 groups. In particular, the response of serum gonadotropin to GnRH correlated to the maturity of the germ cells. Spermatogenesis could be initiated by hCG alone in IHH patients without cryptorchidism. Normal sperm density was obtained by hCG alone in the case of mild IHH; however, in moderate and severe IHH groups, hMG-hCG therapy was required for sufficient spermiogenesis. Sexual maturation was completely obtained by gonadotropin therapy within 1 year in moderate and mild IHH. However, in severe IHH, satisfactory sexual maturation could not be obtained within 1 year. The therapeutic prognosis for sexual maturation could be made based on the response to the hCG test at 6 months of gonadotropin therapy. In conclusion, the maturity of germ cells before treatment, which varies widely among patients with IHH, is a sensitive parameter for hypothalamo-pituitary-testicular function and the efficacy of gonadotropin therapy for testicular function. In severe IHH groups, to obtain satisfactory sexual maturation, the administration of testosterone should be considered in addition to gonadotropin replacement.

Adolescent↗
PubMed1995

A macrocircular ellagitannin, oenothein B, suppresses mouse mammary tumor gene expression via inhibition of poly(ADP-ribose) glycohydrolase.

Oenothein B, a macrocircular dimeric ellagitannin, was found to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. Oenothein B suppressed glucocorticoid-sensitive mouse mammary tumor virus (MMTV) transcription in 34I cells. This suppression was accompanied by inhibition of glucocorticoid-induced endogeneous de-poly(ADP-ribosyl)ation of high mobility group (HMG) 14 and 17 proteins. These results suggest that de-poly(ADP-ribosyl)ation of these proteins may be closely connected with the events initiating glucocorticoid-sensitive MMTV gene transcription.

Animals↗
PubMed1995

Synthetic peptides derived from midkine enhance plasminogen activator activity in bovine aortic endothelial cells.

Chemically synthesized human midkine enhanced plasminogen activator activity and decreased its inhibitor levels in bovine aortric endothelial cells. These activities were preserved in the C-terminal half, but not in the N-terminal half of the midkine molecule. Furthermore, a synthetic peptide of 43 amino acids designated as "C-domain", which formed the compact structure held by two disulfide bonds in the C-terminal half, mimicked intact midkine. Chemically synthesized C-domain of pleiotrophin (43 amino acids), which was 53% identical to midkine C-domain in amino acid sequence, expressed the similar activities. These 43 amino acid peptides are, so far, the shortest peptide able to enhance the fibrinolytic activities of the endothelial cells.

Amino Acid Sequence↗
PubMed1995

Molecular cloning of a novel mitogen-inducible nuclear protein with a Ran GTPase-activating domain that affects cell cycle progression.

We have cloned a novel cDNA (Spa-1) which is little expressed in the quiescent state but induced in the interleukin 2-stimulated cycling state of an interleukin 2-responsive murine lymphoid cell line by differential hybridization. Spa-1 mRNA (3.5 kb) was induced in normal lymphocytes following various types of mitogenic stimulation. In normal organs it is preferentially expressed in both fetal and adult lymphohematopoietic tissues. A Spa-1-encoded protein of 68 kDa is localized mostly in the nucleus. Its N-terminal domain is highly homologous to a human Rap1 GTPase-activating protein (GAP), and a fusion protein of this domain (SpanN) indeed exhibited GAP activity for Rap1/Rsr1 but not for Ras or Rho in vitro. Unlike the human Rap1 GAP, however, SpanN also exhibited GAP activity for Ran, so far the only known Ras-related GTPase in the nucleus. In the presence of serum, stable Spa-1 cDNA transfectants of NIH 3T3 cells (NIH/Spa-1) hardly overexpressed Spa-1 (p68), and they grew as normally as did the parental cells. When NIH/Spa-1 cells were serum starved to be arrested in the G1/G0 phase of the cell cycle, however, they, unlike the control cells, exhibited progressive Spa-1 p68 accumulation, and following the addition of serum they showed cell death resembling mitotic catastrophes of the S phase during cell cycle progression. The results indicate that the novel nuclear protein Spa-1, with a potentially active Ran GAP domain, severely hampers the mitogen-induced cell cycle progression when abnormally and/or prematurely expressed. Functions of the Spa-1 protein and its regulation are discussed in the context of its possible interaction with the Ran/RCC-1 system, which is involved in the coordinated nuclear functions, including cell division.

3T3 Cells↗
PubMed1995

Eye scanning behavior as a discriminator of instrument- and scenery-centered flight task.

Aircraft pilot's eye scanning behavior represented by saccadic amplitudes and dwelling time of eye movements is a promising indicator of discrimination whether some flight task is instrument- or scenery-centered. The saccadic amplitude seems to reflect spatial and temporal values of target information. The dwelling time or gaze duration reflects the changing rate of visual information, amounts extracted from and density and complexity of the target information, or experience level of a relevant pilot. This study is for confirming the validity of the above indicator to discriminate the two types of flight tasks, instrument- and scenery-centered tasks. Five jet aircraft pilots, aged 25 to 32, participated in this experiment. A flight simulator equipped with a computer generated visual scene (field of view: 116 degree (H) x 25 degree (V)) was used. Five kinds of flight tasks were selected. These were takeoff, level flight, low-airspeed flight, acrobatic flight (minimum timed turn), and landing. These tasks were selected with the difference in degree of instrument- or scenery-centered flight, by the pilots' comments. Eye movements during simulator flight were recorded by a conventional electrooculographic apparatus with an 12-channel polygraph system. Analogue data from the amplifiers was digitized at a sampling rate of 2 kHz, and stored in a computer system. Horizontal components of eye movements by flight task were analyzed. Mean saccadic amplitudes (microV) showed significant differences among flight tasks, and no significance between subjects was obtained. The largest mean amplitude was in the acrobatic flight, and the smallest was in the low-airspeed flight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗