Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 127 records · Page 7Linked to original sources

PubMed2000

Anti-Ri-associated paraneoplastic cerebellar degeneration without opsoclonus in a patient with a neuroendocrine carcinoma of the stomach.

We report a case of a 63-year-old man suffering from anti-Ri-associated paraneoplastic cerebellar degeneration (PCD) with gastric cancer. The neurologic presentation was limited to severe cerebellar ataxia without opsoclonus. The gastric cancer was composed of both poorly differentiated adenocarcinoma and neuro-endocrine carcinoma. The patient's serum reacted with recombinant Ri antigen and the neuroendocrine tumor component. It is thus considered that PCD without opsoclonus in the present case was related to the gastric neuroendocrine tumor and anti-Ri antibody.

Adenocarcinoma↗

PubMed2000

[Wilms' tumors and malformation complexes].

Wilms' tumor is an embryonal tumor which is derived from metanephric metanephric blastema. The occurrence of both sporadic and hereditary forms, along with various congenital abnormalities of Wilms' tumor suggest that the tumors develop when a predisposing germ line mutation is accompanied by a second mutation. The existence of both gross chromosomal abnormalities has led to the genetic characterization of a number of loci involved in the development of Wilms' tumor. A tumor suppressor gene for Wilms' tumor, WT1, has been isolated from the 11p13 region. The product of this gene is a transcription factor with four zinc fingers. Because of expression of WT1 is limited to the developing glomeruli of the kidneys and the genital ridge, it is thought to have a functional role in renal and gonadal organogesis. Thus dysfunction of WT1 causes loss of normal regulation of proliferation and leads to tumor formation and occurrence of Wilms' tumor anomaly complexes. The role of the imprinting genes, H19 and IGF2 in oncogenesis of Wilms' tumors are also discussed.

Chromosome Aberrations↗

PubMed2000

[Leukocytopenia and thrombocytopenia preceded by human parvovirus B19 infection: report of three adult cases].

In Saiki City, Oita, Japan, erythema infectiosum in children has been prevalent from June, 1999 to the time of writing (January, 2000). We present three adult cases of parvovirus B19-associated leukocytopenia and thrombocytopenia that developed during this epidemic. Between June and November, 1999, a 32-year-old woman, a 38-year-old woman, and a 63-year-old man were referred to our hospital for treatment of leukocytopenia and thrombocytopenia. All complained of common cold-like symptoms. Their WBC counts (percentage of neutrophils) were 1,000/microliter (70%), 1,900/microliter (40%) and 1,680/microliter (40%), their hemoglobin levels 9.4 g/dl, 9.8 g/dl and 14.9 g/dl, and their platelet counts 10.8 x 10(4)/microliter, 6.9 x 10(4)/microliter and 4.5 x 10(4)/microliter, respectively. The diagnosis of parvovirus B19 infection was documented by the presence of B19-specific IgM antibodies or serum positivity for viral DNA. In two cases, the leukocytopenia and thrombocytopenia resolved gradually. In the other case, leukocytopenia, thrombocytopenia and B19 infection persisted for more than two months. These cases suggest that parvovirus B19 may be a common cause of leukocytopenia and thrombocytopenia even in adult patients without hematological disorders (erythropoietic stress), and that testing for parvovirus infection is justified in such patients, even if anemia is slight, especially when erythema infectiosum is prevalent.

Adult↗

PubMed2000

[Combined endovascular stent implantation and coil embolization for the treatment of a vertebro-basilar fusiform aneurysm: technical case report].

We describe a case of the combined application of endovascular stent implantation and Guglielmi detachable coil packing for the treatment of a vertebro-basilar fusiform aneurysm and review the literature on stent placement to treat cerebral aneurysms. A 70-year-old female presented with an acute headache from subarachnoid hemorrhage. A fusiform aneurysm with a broad-based neck and dome, measuring 15 mm, involving the union of the vertebral arteries and the proximal basilar artery was demonstrated on cerebral angiography. The aneurysm was judged to be inoperable and treated conservatively. Twelve days later the patient was transferred to our hospital for endovascular therapy. An intravascular stent (MultiLink) was placed across the base of the aneurysm through the right vertebral artery. After this, coil placement in the aneurysm around the stent was performed via a microcatheter guided from the left vertebral artery. After that a microcatheter was guided from the right vertebral artery through the interstices of the stent into the aneurysm, and additional coils were placed. Final angiography showed subtotal occlusion of the aneurysm and excellent blood flow of the parent artery through the stent. There were no new neurological deficits. Neither rerupture nor ischemic event has occurred. The use of stents provides another treatment for managing the difficult entity of intracranial aneurysms.

Acute Disease↗

PubMed2000

[The effects of human atrial natriuretic peptide on the pediatric recipients of living-related renal transplantation].

We evaluated the effects of human natriuretic peptide (hANP) on the recipients of living-related renal transplantation in children. Anesthesia was maintained with nitrous-oxide and isoflurane in oxygen. The recipients were divided into two groups: the hANP group (n = 8) received continuous infusion of hANP (0.1 microgram.kg-1.min-1), and the control group (n = 5) received no hANP infusion. Intravenous hANP infusion was started at the loading time of fresh frozen plasma in the recipients until the 12 hours after operation. There were no differences between the groups with regards to age, height, body weight, changes in heart rate and systolic arterial pressure, urine volume during operation, and the levels of blood uremic nitrogen and creatinine. The hANP group showed minimal change in CVP during operation and body weight between the values during and after operation compared with control group. The control group needed significantly more fluid than hANP group during operation. We concluded that continuous i.v. hANP infusion in the pediatric recipients of living-related renal transplantation was useful for maintaining sufficient urination and prevention of heart failure or lung edema.

Anesthesia, General↗

PubMed1999

Gene delivery using liposome technology.

Development of more reliable liposomal formulations and preparation methods which can be used for gene therapy instead of commonly used viral vectors is expected. We have already developed the freeze-dried empty (non-drug-containing) liposomes (FDEL) method for mass-production of liposomal products. After these freeze-dried empty liposomes are rehydrated with aqueous drug solutions, many kinds of drugs can be encapsulated highly efficiently, and particle size can be controlled well. This study evaluated the usefulness of this FDEL method for preparation of liposomes containing DNA with a particular attention to the stability of DNA. When the liposomes were prepared by the conventional lipid-film method on a relatively large scale with use of a Potter-homogenizer (a teflon homogenizer), significant degradation and conformational change of DNA was observed during homogenization. Loss of DNA was also significant after extrusion for sizing and sterilization; residual DNA in the final preparation was hardly detected. When the FDEL method was used, on the other hand, no degradation, conformational change or loss of DNA was observed, and particle size was easily controlled. Moreover, there was no significant difference in luciferase activity between the lipid-film method used on a small scale with use of a vortex mixer and the FDEL method after transfection of tumor cells (HRA, HEC-1A and Colo320DM) by the liposomes containing DNA (PGV-C). These findings suggest that the FDEL method is very useful for preparation of liposomes containing DNA.

DNA↗

PubMed1999

Chicken histone deacetylase-2 controls the amount of the IgM H-chain at the steps of both transcription of its gene and alternative processing of its pre-mRNA in the DT40 cell line.

Histone deacetylases (HDACs) are involved in the deacetylation of core histones, which is an important event in transcription regulation in eukaryotes through alterations in the chromatin structure. We cloned cDNAs and genomic DNAs encoding two chicken HDACs (chHDAC-1 and -2), which are preferentially localized in nuclei. Treatment with trichostatin A reduced the HDAC activities in immunoprecipitates obtained with anti-chHDAC-1 and -2 antisera. Using gene targeting techniques, we generated homozygous DT40 mutants, DeltachHDAC-1 and -2, devoid of two alleles of the chHDAC-1 and -2 genes, respectively. The protein patterns on two-dimensional PAGE definitely changed for DeltachHDAC-2, and the amounts of the IgM H- and L-chains increased in it. Of the two IgM H-chain forms, the secreted form mu(s) increased in DeltachHDAC-2, but the membrane-bound form mu(m) decreased. The IgM H-chain gene was transcribed more in DeltachHDAC-2 than in DT40 cells. In the mutant, the alternative processing of IgM H-chain pre-mRNA preferentially occurred, resulting in an increase in the amount of mu(s) mRNA, whereas the stability of the two types of mRNA, mu(s) and mu(m), was unchanged. In DT40 cells, treatment with trichostatin A increased both the amounts of IgM H-chain mRNAs and the switch from mu(m) to mu(s) mRNAs. Based on these results, we propose a model for a role of chHDAC-2 in both the transcription and alternative processing steps, resulting in control of the amount of the mu(s) IgM H-chain in the DT40 cell line.

Amino Acid Sequence↗

PubMed1999

Thermostable flap endonuclease from the archaeon, Pyrococcus horikoshii, cleaves the replication fork-like structure endo/exonucleolytically.

The flap endonuclease gene homologue from the hyperthermophilic archaeon, Pyrococcus horikoshii, was overexpressed in Escherichia coli and purified. The results of gel filtration indicated that this protein was a 41-kDa monomer. P. horikoshii flap endonuclease (phFEN) cleaves replication fork-like substrates (RF) and 5' double-strand flap structures (DF) using both flap endonuclease and 5'-3'-exonuclease activities. The mammalian flap endonuclease (mFEN) is a single-strand flap-specific endonuclease (Harrington, J. J., and Lieber, M. R. (1994) EMBO J. 13, 1235-1246), but the action patterns of phFEN appear to be quite different from those of mFEN at this point. The DF-specific flap endonuclease and 5'-exonuclease activities have not yet been reported. Therefore, this is the first report of the specific endo/exonuclease activities of phFEN. The DF-specific 5'-exonuclease activity degraded the downstream primer of 3' single-flap structure and was 15 times higher than the activities against nicked substrates without 3' flap strand. DF-specific flap endonuclease cleaved the 5' double-flap strand in DF and the lagging strand in RF at the junction portion. Because the RF appears to be the intermediate structure, due to the arrest of the replication fork, the double strand breaks after the arrests of the replication forks are probably caused by phFEN.

Amino Acid Sequence↗

PubMed1999

Evaluation of cationic liposome suitable for gene transfer into pregnant animals.

Cationic liposome-mediated in vivo gene transfer represents a promising approach for somatic gene therapy. To assess the most suitable liposome for gene delivery into a wide range of organs and fetuses in mice, we have explored several types of cationic liposomes conjugated with plasmid DNA carrying the beta-galactosidase gene through intravenous injection into pregnant animals. Transduction efficiency was assessed by Southern blot analysis and expression of the transferred gene was evaluated by enzymatic demonstration of beta-galactosidase activity. Through the analysis of several types of recently synthesized cationic liposome/lipid formulations, DMRIE-C reagent, a liposome formulation of the cationic lipid DMRIE (1, 2-dimyristyloxypropyl-3-dimethyl-hydroxy ethyl ammonium bromide) and cholesterol in membrane-filtered water met our requirements. When the plasmid DNA/DMRIE-C complexes were administered intravenously into pregnant mice at day 11.5 post coitus (p.c.), transferred genes were observed in several organs in dams and were expressed. Furthermore, although the copy numbers transferred into embryos were low, we observed reporter gene expression in the progeny.

Animals↗

PubMed1999

Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1.

The complete sequence of the genome of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1, which optimally grows at 95 degrees C, has been determined by the whole genome shotgun method with some modifications. The entire length of the genome was 1,669,695 bp. The authenticity of the entire sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2,694 open reading frames (ORFs) were assigned. By similarity search against public databases, 633 (23.5%) of the ORFs were related to genes with putative function and 523 (19.4%) to the sequences registered but with unknown function. All the genes in the TCA cycle except for that of alpha-ketoglutarate dehydrogenase were included, and instead of the alpha-ketoglutarate dehydrogenase gene, the genes coding for the two subunits of 2-oxoacid:ferredoxin oxidoreductase were identified. The remaining 1,538 ORFs (57.1%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs suggested that a considerable member of ORFs were generated by sequence duplication. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 47 tRNA genes including 14 genes with intron structures. All the assigned ORFs and RNA coding regions occupied 89.12% of the whole genome. The data presented in this paper are available on the internet homepage (http://www.mild.nite.go.jp).

Archaea↗

PubMed1999

Development of novel cationic liposomes for efficient gene transfer into peritoneal disseminated tumor.

A novel series of cationic lipids has been found, by in vivo screening, to be effective for gene transfer into peritoneal disseminated tumor. O,O'-Ditetradecanoyl-N-(alpha-trimethylammonioacetyl)diethan olamine chloride (DC-6-14), having dimyristyl acid, has shown the highest transfection activity in vitro, provided that 10% fetal bovine serum is present. To enhance the transfection efficiency of DC-6-14, we added dioleoylphosphatidylethanolamine (DOPE) and/or cholesterol (Chol) as helper lipids in various ratios. Cationic liposomes containing DC-6-14, DOPE, and Chol in molar ratios of 1:0.75:0.75 and 1:1:0.8 maintained efficient transfection activity under serum-containing conditions in HRA, mEIIL, and ES-2 cell lines in vitro, as determined by luciferase assay. With our novel liposomes, transfection efficiencies were higher in cells proliferating faster than in cells proliferating slower, depending on mitotic activity as represented by labeling index. In the mEIIL peritoneal disseminated tumor model, cancer cells were specifically transfected with the lacZ gene. Gene transfer was observed by X-Gal staining not only in floating cancer cells in the ascites, but also in the peritoneal disseminated cancer tissue. The percentage of LacZ-positive cells was about 1%, which was significantly higher than with commercially available Lipofectin (0.38%), LipofectACE (0.62%), or LipofectAMINE (0.23%). In the mEIIL peritoneal disseminated tumor-nude mouse model, herpes simplex thymidine kinase gene (HSV tk) transfer with our novel liposomes, followed by ganciclovir (GCV) treatment, resulted in significantly longer survival compared with control mice (p < 0.05, Cox-Mantel). These results suggest that these liposomes show promise as tools in gene therapy for patients with intraperitoneal disseminated cancer.

Animals↗

PubMed1999

Thermostable aminopeptidase from Pyrococcus horikoshii.

From the genome sequence data of the thermophilic archaeon Pyrococcus horikoshii, an open reading frame was found which encodes a protein (332 amino acids) homologous with an endoglucanase from Clostridium thermocellum (42% identity), deblocking aminopeptidase from Pyrococcus furiosus (42% identity) and an aminopeptidase from Aeromonas proteolytica (18% identity). This gene was cloned and expressed in Escherichia coli, and the characteristics of the expressed protein were examined. Although endoglucanase activity was not detected, this protein was found to have aminopeptidase activity to cleave the N-terminal amino acid from a variety of substrates including both N-blocked and non-blocked peptides. The enzyme was stable at 90 degrees C, with the optimum temperature over 90 degrees C. The metal ion bound to this enzyme was calcium, but it was not essential for the aminopeptidase activity. Instead, this enzyme required the cobalt ion for activity. This enzyme is expected to be useful for the removal of N(alpha)-acylated residues in short peptide sequence analysis at high temperatures.

Aminopeptidases↗

PubMed1999

Mucoadhesion of polystyrene nanoparticles having surface hydrophilic polymeric chains in the gastrointestinal tract.

The mucoadhesion of polystyrene nanoparticles having surface hydrophilic polymeric chains in the gastrointestinal (GI) tract was investigated in rats. Radiolabeled nanoparticles were synthesized by adding hydrophobic 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine in the final process of nanoparticle preparation. The radioiodonated diazirine seemed to be incorporated in the hydrophobic polystyrene core of nanoparticles. The incorporation rate was less than 10%, irrespective of nanoparticle type. The diazirine incorporated in nanoparticles exhibited little leakage from them even though they were mixed with a solution corresponding to GI juice. The change in blood ionized calcium concentration after oral administration of salmon calcitonin (sCT) with nanoparticles showed that the in vivo enhancement of sCT absorption by radiolabeled nanoparticles was the same as that by non-labeled nanoparticles. The GI transit rates of nanoparticles having surface poly(N-isopropylacrylamide), poly(vinylamine) and poly(methacrylic acid) chains, which can improve sCT absorption, were slower than that of nanoparticles covered by poly(N-vinylacetamide), which does not enhance sCT absorption at all. These slow transit rates were probably the result of mucoadhesion of nanoparticles. The strength of mucoadhesion depended on the structure of the hydrophilic polymeric chains on the nanoparticle surface. The mucoadhesion of poly(N-isopropylacrylamide) nanoparticles, which most strongly enhanced sCT absorption, was stronger than that of ionic nanoparticles, and poly(N-vinylacetamide) nanoparticles probably did not adhere to the GI mucosa. These findings demonstrated that there is a good correlation between mucoadhesion and enhancement of sCT absorption.

Analgesics↗

PubMed1999

Substrate recognition by class I lysyl-tRNA synthetases: a molecular basis for gene displacement.

Lysyl-tRNA synthetases (LysRSs) are unique amongst the aminoacyl-tRNA synthetases in being composed of unrelated class I and class II enzymes. To allow direct comparison between the two types of LysRS, substrate recognition by class I LysRSs was examined. Genes encoding both an archaeal and a bacterial class I enzyme were able to rescue an Escherichia coli strain deficient in LysRS, indicating their ability to functionally substitute for a class II LysRS in vivo. In vitro characterization showed lysine activation and recognition to be tRNA-dependent, an attribute of several class I, but not class II, aminoacyl-tRNA synthetases. Examination of tRNA recognition showed that class I LysRSs recognize the same elements in tRNALys as their class II counterparts, namely the discriminator base (N73) and the anticodon. This sequence-specific recognition of the same nucleotides in tRNALys by the two unrelated types of enzyme suggests that tRNALys predates at least one of the LysRSs in the evolution of the translational apparatus. The only observed variation in recognition was that the G2.U71 wobble pair of spirochete tRNALys acts as antideterminant for class II LysRS but does not alter class I enzyme recognition. This difference in tRNA recognition strongly favors the use of a class I-type enzyme to aminoacylate particular tRNALys species and provides a molecular basis for the observed displacement of class II by class I LysRSs in certain bacteria.

Amino Acyl-tRNA Synthetases↗

PubMed1999

Reactive oxygen species production of neutrophils in patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid.

We measured N-formyl-methionyl-leucyl-phenylalanine-induced reactive oxygen species production by neutrophils from three patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid using a luminol-enhanced chemiluminescence assay. The maximum level of reactive oxygen species production during all-trans retinoic acid treatment was 58.8 +/- 2.3 x 10(4) (mean +/- SEM) counted photons per seconds (cps), which was significantly higher (p<0.0001) than that of neutrophils from health volunteers (13.3 +/- 2.3 x 10(4) cps).

Antineoplastic Agents↗

PubMed1999

Synergistic inhibition of human B cell activation by gold sodium thiomalate and auranofin.

The mechanism of action of gold compounds, which are effective in the treatment of rheumatoid arthritis (RA), has not been clearly identified. Since one of the characteristic features of RA is chronic stimulation of B cells, the current studies compared the effects of parenteral gold (gold sodium thiomalate; GST) and orally active gold (auranofin; AUR) on human B cells. IgM production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. T cell proliferation and IFN-gamma production was induced from highly purified T cells by stimulation with immobilized mAb to CD3. AUR as well as GST suppressed B cell IgM production at much lower concentrations than those that suppressed T cell proliferation or IFN-gamma production. Thus, as little as 0.01 microg/ml AUR (0.015 microM) markedly suppressed IgM production, but neither T cell proliferation nor IFN-gamma production. AUR as well as GST is required at the initiation of cultures to exert optimal suppressive effects on IgM production. Moreover, AUR as well as GST suppressed the expression of CD98 and CD71 on SA-stimulated B cells. Of note, AUR and GST exerted a synergistic inhibitory effect on B cell production of IgM and IgG in a manner which was reversed by catalase, but not by ascorbate. The synergistic inhibitory effect is most likely to be due to thiomalate components of GST, since AUR and thiomalate exerted comparable synergistic inhibitory effects on B cell function. Finally, AUR and bucillamine, another antirheumatic drug with thiol groups, also showed synergistic inhibition of B cell function. These results indicate that AUR and GST preferentially inhibit the function of B cells by interfering with the initial activation of B cells. More importantly, the data indicate that AUR synergizes with GST or thiols to inhibit B cell function in a manner that depends upon the generation of hydrogen peroxide. These synergistic inhibitory effects of AUR and compounds with thiols on in vitro human B cell activation suggest the therapeutic efficacy of combinations of these compounds in RA.

Auranofin↗

PubMed1999

Endovascular treatment of aneurysms on the feeding arteries of intracranial arteriovenous malformations.

The association between intracranial aneurysms and arteriovenous malformations (AVMs) is well documented. Recent advances in the understanding of the haemodynamics of this association encourage an aggressive approach to these aneurysms. However, the pathophysiology of these aneurysms is not fully understood and a strategy for their management has not been established. We describe seven patients, with eight aneurysms, on the feeding arteries of AVMs. The aneurysms could be divided into those located 1. proximally on the superficial feeding artery (type I; 4 aneurysms); 2. distally on the superficial feeding artery (type II; 3 aneurysms); and 3. on the deep feeding artery (type III; 1 aneurysm). All aneurysms were treated by the endovascular procedure prior to, or simultaneously with, treatment of the AVM, using detachable coils or liquid embolic material. All aneurysms were obliterated successfully, with no adverse events. Each patient further received treatment of the AVM. None of the patients suffered intracranial haemorrhage after treatment for the aneurysms. Based on our experiences, we discuss the indications for this approach for each type of aneurysm. We believe endovascular treatment could be an important alternative for treatment of aneurysms associated with AVMs, thus reducing the risk of haemorrhage.

Adult↗

PubMed1999

Immunohistochemical analysis of spinal cord lesions in amyotrophic lateral sclerosis using microtubule-associated protein 2 (MAP2) antibodies.

We have studied microtubule-associated protein 2 (MAP2) expression in anterior horn neurons in the cervical and lumbar spinal cords of 19 cases of adult-onset sporadic amyotrophic lateral sclerosis (ALS) using immunohistochemistry. Specimens from 7 patients without neurological disease served as controls. MAP2 expression decreased in the anterior gray horn of all ALS cases and in the intermediate gray of several ALS cases. Such reduction correlated with the degree of degeneration or neuronal loss in anterior horn cells and with the clinical symptoms of limb weakness. Cytopathologically, the MAP2 immunoreactivity decreased corresponding to the occurrence of individual signs of neuronal degeneration, such as chromatolytic neurons, shrunken neurons and pigmented neurons. MAP2 expression was relatively well preserved in the specimens in which spheroids are conspicuous. The findings of this study demonstrate MAP2 to be an excellent marker for the detection and quantification of anterior horn degeneration in ALS.

Aged↗