Low-dose cytarabine (LD-AraC) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for myelodysplastic syndromes (MDS)
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Adolescent↗
Biomedical subjects
A Kikuchi
Publications and source records attributed to A Kikuchi.
Growth factor and matrix molecules preserve cell function on thermally responsive culture surfaces.
Thermally-responsive culture surfaces were designed using copolymers of N-isopropylacrylamide, 4-(aminomethyl)styrene, and acrylic acid. These surfaces contained functional amine and carboxyl groups, which allowed biomolecules to be grafted by amide formation. Epidermal growth factor (EGF), and extracellular matrix (ECM) molecules (collagen type IV, and chondroitin sulfate) were investigated, as surface-grafted biomolecules, for their ability to stimulate cell attachment, proliferation, and function by signaling only from the basal side of cultured cells. Surface analysis of biomolecule-grafted porous inserts showed covalent binding of biomolecules to either amine or carboxyl groups. Multiple attachment to amine and/or carboxyl groups served as cross-linking points that made the polymer hydrogel permanently adherent to the culture surface. Immunofluorescence microscopy techniques gave positive identification of grafted biomolecules. Grafting of EGF improved cell proliferation versus that on nongrafted controls, or controls grafted only with ECM molecules. ECM grafting induced cell attachment on attachment-resistant surfaces. Analysis of trans-epithelial resistance, fluid transport, and polarized g-glutamyl transpeptidase activity indicated that simultaneous grafting of both EGF and ECM produced better polarized cell function than nongrafted controls, or controls grafted with only one type of biomolecule. Covalent grafting of biomolecules did not interfere with cells ability to detach from thermally responsive surfaces upon temperature decrease.
Amides↗
A clinicopathological study of postoperative pulmonary metastasis of uterine cervical carcinomas.
OBJECTIVE: To investigate the clinicopathological backgrounds and prognostic factors of uterine cervical carcinomas metastatic to the lung. METHODS: A total of 519 patients with invasive cervical carcinoma (Stage pTIb-IIb) treated by abdominal radical hysterectomy at the Saitama Cancer Center from January 1, 1976 to December 31, 1989 were analyzed clinicopathologically. RESULTS: The frequencies of pulmonary metastasis were 6.4% (24/377) and 11.3% (16/142) in patients with negative and positive pelvic lymph nodes, respectively. Among 24 negative lymph node patients, 15 had pulmonary metastasis only. The overall 5-year survival rate of these 15 patients was 36% after relapse. Of the 15, the prognosis of 12 patients with 1-3 pulmonary metastases only was better, that is, 46% after surgical resection (mean size of resectable tumor = 2.8 cm) and/or chemotherapy. But the other patients died within 3.3 years after relapse. CONCLUSIONS: The occurrence of pulmonary metastasis only, its number (1-3) and size (mean size = 2.8 cm), and no lymph node metastasis are important prognostic factors. For these patients, active surgical resection of the pulmonary lesion(s) and further chemotherapy are recommended in order to improve their prognosis.
Adenocarcinoma↗
Possible susceptibility of the HLA-DPB1*0402 and HLA-DPB1*04 alleles to unexplained recurrent abortion: analysis by means of polymerase chain reaction-restricted fragment length polymorphism method.
PROBLEM: To clarify whether HLA-DP antigens are associated with patient population of unexplained recurrent abortion. METHOD OF STUDY: The frequency of HLA-DPB1 alleles in patients with unexplained recurrent abortion, and the compatibility of HLA-DPB1 alleles between patient couples, were studied using a polymerase chain reaction (PCR)-restricted fragment length polymorphism (RFLP) method. Thirty patients who had a history of unexplained primary recurrent abortion, and their husbands, were typed for HLA-DPB1 genotype. Two hundred and ninety-nine base pair fragments from the second exon of HLA-DPB1 genes were selectively amplified using the PCR-primers. After amplification, the DNAs were digested with restriction endonucleases, and subjected to electrophoresis in a 12% polyacrilamide gel to determine HLA-DPB1 genotype. RESULTS: The frequency of HLA-DPB1*0402 and DPB1*04 alleles in the patient group (n = 30) was significantly increased, as compared to that in the normal fertile women (n = 30). The frequency of HLA-DPB1*04 allele in the patient group was significantly increased, as compared to that in the general population (n = 112). No significant compatibility of HLA-DPB1 alleles could be observed between patient couples and normal fertile couples. CONCLUSION: These findings suggest a possible new class II association with patient population of unexplained recurrent abortion.
Abortion, Habitual↗
Sperm chromatin decondensation by template activating factor I through direct interaction with basic proteins.
Template activating factor I (TAF-I) was originally identified as a host factor required for DNA replication and transcription of adenovirus genome complexed with viral basic proteins. Purified TAF-I was shown to bind to core histones and stimulate transcription from nucleosomal templates. Human TAF-I consists of two acidic proteins, TAF-Ialpha and TAF-Ibeta, which differ from each other only in their amino-terminal regions. Here, we report that TAF-I decondenses demembraned Xenopus sperm chromatin. Human TAF-Ibeta has a chromatin decondensation activity comparable to that of NAP-I, another histone binding protein, whereas TAF-Ialpha has only a weak activity. Analysis of molecular mechanisms underlying the chromatin decondensation by TAF-I revealed that TAF-I interacts directly with sperm basic proteins. Deletion of the TAF-I carboxyl-terminal acidic region abolishes the decondensation activity. Interestingly, the acidic region itself is not sufficient for decondensation, since an amino acid substitution mutant in the dimerization domain of TAF-I which has the intact acidic region does not support chromatin decondensation. We detected the beta form of TAF-I in Xenopus oocytes and eggs by immunoblotting, and the cloning of its cDNA led us to conclude that Xenopus TAF-Ibeta also decondenses sperm chromatin. These results suggest that TAF-I plays a role in remodeling higher-order chromatin structure as well as nucleosomal structure through direct interaction with chromatin basic proteins.
Amino Acid Sequence↗
DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability.
The N-terminal region of Dvl-1 (a mammalian Dishevelled homolog) shares 37% identity with the C-terminal region of Axin, and this related region is named the DIX domain. The functions of the DIX domains of Dvl-1 and Axin were investigated. By yeast two-hybrid screening, the DIX domain of Dvl-1 was found to interact with Dvl-3, a second mammalian Dishevelled relative. The DIX domains of Dvl-1 and Dvl-3 directly bound one another. Furthermore, Dvl-1 formed a homo-oligomer. Axin also formed a homo-oligomer, and its DIX domain was necessary. The N-terminal region of Dvl-1, including its DIX domain, bound to Axin directly. Dvl-1 inhibited Axin-promoted glycogen synthase kinase 3beta-dependent phosphorylation of beta-catenin, and the DIX domain of Dvl-1 was required for this inhibitory activity. Expression of Dvl-1 in L cells induced the nuclear accumulation of beta-catenin, and deletion of the DIX domain abolished this activity. Although expression of Axin in SW480 cells caused the degradation of beta-catenin and reduced the cell growth rate, expression of an Axin mutant that lacks the DIX domain did not affect the level of beta-catenin or the growth rate. These results indicate that the DIX domains of Dvl-1 and Axin are important for protein-protein interactions and that they are necessary for the ability of Dvl-1 and Axin to regulate the stability of beta-catenin.
Adaptor Proteins, Signal Transducing↗
Fetal size as a determinant of obstetrical outcome of post-term pregnancy.
HYPOTHESIS: We hypothesized that there might be differences in the outcomes of post-term pregnancy according to fetal size. METHODS: A retrospective analysis of 143 women with uncomplicated pregnancy that persisted beyond 42 weeks was conducted. Ultrasound dating was performed between 8 and 14 weeks in all cases. The obstetrical outcomes were compared between the cases in which neonatal birth weight was <3,600 g (non-large group) and >/= 3,600 g (large group). RESULTS: In primiparous women, there was no significant difference between the non-large and large groups in terms of the rate of cesarean section, but the rate of cesarean section for fetal distress in the non-large group was significantly higher than that found in the large group. In addition, the non-large group showed a significantly higher incidence of low pH (<7.20) compared with the large group (14/58 vs. 0/22, p < 0.01). In contrast, the rate of prolonged labor (>24 h) and induction failure in the non-large group were significantly lower than that in the large group. In multiparous women, there was no significant difference in obstetrical outcomes between the non-large and large groups. CONCLUSIONS: Primiparous women who were delivered of fetuses weighing not less than 3,600 g at post-term periods were at lower risk of fetal distress on the one hand and at higher risk of induction failure associated with infavorable cervix on the other. This study suggests that post-term pregnancy should be dealt with differently based on fetal weight.
Birth Weight↗
Goat fetuses disconnected from the placenta, but reconnected to an artificial placenta, display intermittent breathing movements.
To investigate whether placental factors are involved in the intermittent breathing movements in goat fetuses, we assessed electrocortical activity (ECoA) and tracheal pressure in 5 fetuses (124-135 days) separated from the placenta and connected for 48 h to an extrauterine fetal incubation system that provided umbilical arteriovenous extracorporeal membrane oxygenation. The fetal physiological condition on this system was almost the same as that in utero for at least 48 h after the preparation. All fetuses showed intermittent low-voltage ECoA and breathing movements. The breathing movements occurred almost exclusively during periods of low- voltage ECoA. The proportions of time spent in low-voltage ECoA and breathing movements were 48-57% and 46-56%, respectively. In conclusion, breathing movements of fetuses on the extrauterine incubation system were episodic, suggesting that intermittent breathing movements are intrinsic to fetuses, independent of placenta-derived factors.
Animals↗
Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers.
Two types of thermo-responsive hydrogels are synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTs) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacryl amide-co-N,N-dimethylacrylamide) (poly(IPAAm-co-DMAAm)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37 degrees C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31 degrees C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36 degrees C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.
Absorption↗
Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata.
The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.
Absorptiometry, Photon↗
Immunohistochemical staining of DNA topoisomerase IIalpha in human gliomas.
OBJECT: The enzyme DNA topoisomerase IIalpha (Topo IIalpha) was tested as a measure of cell proliferation in gliomas. METHODS: Immunostaining for the Topo IIalpha and for the Ki-67 antigen (MIB-1 antibody) was performed in paraffin-embedded tissue sections obtained from 25 resected human gliomas. Additionally, cultured human glioma cells were subjected to simultaneous flow cytometry to determine Topo IIalpha and DNA content. Using flow cytometric analysis, the authors found that the Topo IIalpha antibody labeled cells in the S, G2, and M phases of the cell cycle and also those in some parts of the G0 and G1 phases. In histological sections, Topo IIalpha showed more distinct staining than MIB-1, particularly in older archival cases. The proliferative indices (PIs) based on cells staining for MIB-1 and Topo IIalpha correlated highly with one another (r = 0.96). The Topo IIalpha PI immunopositivity was seen in 4.07% of cells in the low-grade astrocytoma group, 11.97% in the anaplastic astrocytoma group, and 13.84% in the glioblastoma multiforme group, representing significant differences between low-grade astrocytoma and both anaplastic astrocytoma and glioblastoma. A Topo IIalpha PI less than 5% predicted longer patient survival (p = 0.003). CONCLUSIONS: Immunostaining for Topo IIalpha represents a useful alternative to MIB-1 as a proliferative index in human gliomas.
Adolescent↗
A first episode of syncope in a veteran pilot: a case report.
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Aerospace Medicine↗
[A case of limbic encephalitis associated with breast cancer developed in an HTLV-1 carrier].
We here present a case of 44-year-old woman, a carrier of human T-lymphotrophic virus type-1 (HTLV-1), who suffered from limbic encephalitis and breast cancer. In December 1997, the patient's behavior became abnormal. Three weeks later, she became markedly forgetful. At that time neurological examinations revealed that she had anterograde and retrograde amnesia, disorientation, and confabulation, although her consciousness was clear. Anti-Hu and anti-Yo antibodies and antinuclear antibodies in the serum were negative. Flow cytometric study of the peripheral blood lymphocytes showed an increased percentage of CD3+CD25+ cells, although the percentages of CD4+CD45RA+ and CD4+CD45RO+ cells were normal. Lymphocytic responses to phytohemagglutinin or concanavalin A were normal. Anti-HTLV-1 antibody was positive both in the serum and in the cerebrospinal fluid (CSF). The level of immunoglobulin G was high and two oligoclonal immunoglobulin G bands were positive in the CSF. Cytological study of the CSF showed no atypical cells. Findings for herpes simplex virus type I and II DNAs were negative with polymerase chain reaction in the CSF. There was no elevation of antibody titers against viruses including herpes simplex virus, cytomegalovirus, and measles virus, either in the serum or the CSF. Magnetic resonance imaging showed signal abnormalities in the medial portions of both temporal lobes, in particular, in the bilateral hippocampus. Six weeks after the onset, a cancerous tumor in her right breast was detected and removed by open surgery. The pathological diagnosis was invasive ductal carcinoma with neuroendocrine features. After mastectomy, anterograde and retrograde amnesia and disorientation mildly improved. The follow-up magnetic resonance imaging showed that signal abnormalities in the medial portions of both temporal lobes decreased and that the bilateral hippocampus became atrophic. We diagnosed the present case as paraneoplastic limbic encephalitis. There has been only one case report of limbic encephalitis associated with breast cancer.
Adult↗
[Heat shock protein 70 (HSP70)].
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HSP70 Heat-Shock Proteins↗
Left coronary artery-left ventricular fistula with acute myocardial infarction, representing the coronary steal phenomenon: a case report.
A 59-year-old man presented with a left anterior descending coronary artery to left ventricular fistula manifesting as myocardial infarction, representing the coronary steal phenomenon. Electrocardiography showed poor R progression in leads V1 through V3. The biochemical markers of myocardial injury were elevated. Creatine kinase level was 509 IU/l, creatine kinase MB isoenzyme (CK-MB)47 IU/l, cardiac troponin T 0.62 ng/ml, myosin light chain 6.1 ng/ml, and myoglobin 142 ng/ml. Thallium-201 myocardial perfusion imaging with dobutamine stress showed a dobutamine-induced perfusion deficit of the anteroseptal wall of the left ventricle with 0.1 mV ST-segment depression in II, III, aVF, V5, and V6. The mean left anterior descending blood flow measured with the Doppler guidewire was increased from 211 to 378 ml/min. Selective coronary arteriography showed dominant left coronary artery with the contrast medium streaming into the left ventricle via a maze of fine vessels from the distal left anterior descending coronary artery. No critical stenosis of the left anterior descending coronary artery was observed. Administration of acetylcholine 100 micrograms into the left coronary artery did not induce vasoconstriction of that artery. The fistula terminating in the left ventricle was ligated surgically and the patient became free of chest pain. Thallium-201 myocardial perfusion imaging with dobutamine stress revealed no perfusion deficit of the anteroseptal wall of the left ventricle. The presence of coronary steal phenomenon was detected by dobutamine stress myocardial imaging.
Coronary Vessel Anomalies↗
Solution structure of the Ras-binding domain of RGL.
The RGL protein, a homolog of the Ral GDP dissociation stimulator (RalGDS), has been identified as a downstream effector of Ras. In the present study, the solution structure of the Ras-binding domain of RGL (RGL-RBD) was determined by NMR spectroscopy. The overall fold of RGL-RBD consists of a five-stranded beta-sheet and two alpha-helices, which is the same topology as that of RalGDS-RBD. The backbone chemical shift perturbation of RGL-RBD upon interaction with the GTP analog-bound Ras was also examined. The solution structure of RGL-RBD, especially around some of the Ras-interacting residues, is appreciably different from that of RalGDS-RBD.
Amino Acid Sequence↗
Identification of Ce-AF-6, a novel Caenorhabditis elegans protein, as a putative Ras effector.
Mammalian Ras proteins associate with multiple effectors, including Raf, Ral guanine nucleotide dissociation stimulator, phosphoinositide 3-kinase and AF-6. In the nematode Caenorhabditis elegans, LIN-45/Raf has been identified genetically as an effector of LET-60/Ras. To search for other effectors in C. elegans, we carried out a yeast two-hybrid screening for LET-60-associating proteins. The screening identified a novel protein, designated Ce-AF-6, which exhibited a strong structural homology with human AF-6, rat Afadin and Drosophila melanogaster Canoe and possessed both the Ras-associating (RA) domain and the PSD-95/DlgA/ZO-1 (PDZ) domain. Ce-AF-6 associated with human Ha-Ras in a GTP-dependent manner, with an efficiency comparable to that of human Raf-1 Ras-binding domain. When the effects of mutations of the Ras effector region residues were examined for associations with various effectors, Ce-AF-6 was found to possess a distinct and the most rigorous requirement for the effector region residues. These results strongly suggest that Ce-AF-6 is a putative effector of Ras that possesses a distinct recognition mechanism for association with Ras.
Amino Acid Sequence↗
Novel therapeutic strategy for atherosclerosis: ribozyme oligonucleotides against apolipoprotein(a) selectively inhibit apolipoprotein(a) but not plasminogen gene expression.
BACKGROUND: Because mechanisms of atherosclerosis by lipoprotein(a) [Lp(a)] have been postulated in the decrease in active transforming growth factor-beta conversion by decreased plasmin, selective decrease in apolipoprotein(a) [apo(a)] independent of plasminogen may have therapeutic values. Although antisense can decrease apo(a), its application may be difficult because of very high homology of apo(a) gene to plasminogen. Thus we used ribozyme strategy that actively cleaves targeted genes to selectively inhibit apo(a) expression. METHODS AND RESULTS: We constructed ribozyme oligonucleotides containing phosphorothioate DNA- and RNA-targeted kringle 4 of the apo(a) gene that showed 80% homology to plasminogen. Transfection of human apo(a) gene produced Lp(a) in medium of HepG2 cells, whereas Lp(a) could not be detected in control cells. Cotransfection of ribozyme and apo(a) gene resulted in the decrease in mRNA of apo(a) but not plasminogen. Moreover, marked decrease in Lp(a) was also observed in the medium transfected with ribozyme and apo(a) gene compared with apo(a) gene alone (P<0.01), whereas there was no significant change in plasminogen level between ribozyme-transfected and control cells. Incubation of human vascular smooth muscle cells (VSMC) with conditioned medium from apo(a)-transfected HepG2 cells resulted in a significant increase in VSMC number, whereas addition of conditioned medium from cells cotransfected with ribozyme oligonucleotides and apo(a) gene resulted in no VSMC growth (P<0.01). DNA-based control oligonucleotides and mismatched ribozyme oligonucleotides did not have an inhibitory effect on Lp(a) production. CONCLUSIONS: Overall, our data revealed that transfection of ribozyme against the apo(a) gene resulted in the selective inhibition of the apo(a) but not the plasminogen gene, providing novel therapeutic strategy for treatment of high Lp(a), a risk factor for atherosclerosis.
Aorta↗