[p53 mutations as prognostic factors of hepatocellular carcinomas].
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Carcinoma, Hepatocellular↗
Biomedical subjects
K Kojima
Publications and source records attributed to K Kojima.
[An adult patient with varicella preceded by acute thrombocytopenia].
A 40-year-old man was admitted to our hospital because of a tendency to bleed. A diagnosis of idiopathic thrombocytopenic purpura was made, and oral prednisolone (1 mg/kg/day) was administered immediately. Three days after admission, hemorrhagic skin rashes highly suggestive of varicella appeared. The oral prednisolone was discontinued, and intravenous gamma-globulin (400 mg/kg/day for 3 days) and aciclovir (750 mg/day for 7 days) were started. The platelet count increased to 254,000/microliter over the next five days, and the skin rashes associated with varicella subsided within a week. We suggest that, in a minority of patients with varicella zoster infection, thrombocytopenia can precede the typical skin rashes, so a search for possible underlying viral infection should be made, and if necessary, immediate treatment started.
Acute Disease↗
A new social care insurance in Japan on 1 April 2000.
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Aged↗
Outline of the medical insurance system in Japan--the change on 1 January 2001.
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Aged↗
Effects of both the emotional behavior and feeding conditions on the circulating plasma volume and plasma glucose levels in cats.
Influence of hypothalamically induced emotional behavior on the circulating plasma volume, plasma levels of glucose, epinephrine (E), norepinephrine (NE), dopamine (DA) and cortisol were examined in awake cats under both fasted and fed conditions. Restlessness was evoked intermittently for 6 h by electrical stimulation of the anteromedial hypothalamus (AMH). Blood was sampled immediately before, 1 h after and 6 h after the start of stimulation. Changes in the plasma volume was calculated by changes of hemoglobin (Hb) and hematocrit (Ht). As the control group, another 7 cats with electrodes implanted but unstimulated were identically treated under both fasted and fed conditions. Both E and glucose levels in restlessness group once markedly increased after 1 h and then tended to decrease after 6 h, whereas NE levels in restlessness group increased after 1 h and further increased after 6 h, whether cats were fasted or fed. DA levels increased under the fasted condition of restlessness. The cortisol level markedly increased in both fasted and fed restlessness groups. The plasma volume in control group increased under the fed condition, while in restlessness group it decreased remarkably and tended to decrease more in a fasted state than in a fed state. These results indicated that AMH induced restlessness elicited marked sympatho-adrenal activation, hyperglycemia and hemoconcentration, whether cats were fasted or fed. Relationship among such responses, and the difference in responses between fasted and fed conditions were also discussed in the paper.
Animals↗
Glycine-rich region of mitochondrial processing peptidase alpha-subunit is essential for binding and cleavage of the precursor proteins.
Mitochondrial processing peptidase, a metalloendopeptidase consisting of alpha- and beta-subunits, specifically recognizes a large variety of mitochondrial precursor proteins and cleaves off amino-terminal extension peptides. The alpha-subunit has a characteristic glycine-rich segment in the middle portion. To elucidate the role of the region in processing functions of the enzyme, deletion or site-directed mutations were introduced, and effects on kinetic parameters and substrate binding of the enzyme were analyzed. Deletion of three residues of the region, Phe(289) to Ala(291), led to a dramatic reduction in processing activity to practically zero. Mutation of Phe(289), Lys(296), and Met(298) to alanine resulted in a decrease in the activity, but these mutations had no apparent effect on interactions between the two subunits, indicating that reduction in processing activity is not due to structural disruption at the interface interacting with the beta-subunit. Although the mutant enzymes, Phe289Ala, Lys296Ala, and Met298Ala, had an approximate 10-fold less affinity for substrate peptides than did that of the wild type, the deletion mutant, delta 289-291, showed an extremely low affinity. Thus, shortening of the glycine-rich stretch led to a dramatic reduction of interaction between the enzyme and substrate peptides and cleavage reaction, whereas mutation of each amino acid in this region seemed to affect primarily the cleavage reaction.
Amino Acid Sequence↗
Low rate of seropositivity to poliovirus among teenagers in Myanmar: A potential pocket for polio.
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Adolescent↗
A proposed common structure of substrates bound to mitochondrial processing peptidase.
Mitochondrial processing peptidase (MPP), a metalloendopeptidase consisting of alpha- and beta-subunits, specifically cleaves off the N-terminal presequence of the mitochondrial protein precursor. Structural information of the substrate bound to MPP was obtained using fluorescence resonance energy transfer (FRET) measurement. A series of the peptide substrates, which have distal arginine residues required for effective cleavage at positions -7, -10, -14, and -17 from the cleavage site, were synthesized and covalently labeled with 7-diethyl aminocoumarin-3-carboxylic acid at the N termini and N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD) at position +4, as fluorescent donor and acceptor, respectively. When the peptides were bound to MPP, substantially the same distances were obtained between the two probes, irrespective of the length of the intervening sequence between the two probes. When 7-diethylamino-3-(4'-maleimidyl phenyl)-4-methyl coumarin was introduced into a single cysteine residue in beta-MPP as a donor and IANBD was coupled either at the N terminus or the +4 position of the peptide substrate as an acceptor, intermolecular FRET measurements also demonstrated that distances of the donor-acceptor pair were essentially the same among the peptides with different lengths of intervening sequences. The results indicate that the N-terminal portion and the portion around the cleavage site of the presequence interact with specific sites in the MPP molecule, irrespective of the length of the intervening sequence between the two portions, suggesting the structure of the intervening sequence is flexible when bound to the MPP.
Amino Acid Sequence↗
Extended-range glucose sensor employing engineered glucose dehydrogenases.
An enzyme glucose sensor with an expanded dynamic range was constructed using a novel strategy. This strategy was based on a new concept of utilizing protein-engineered enzymes with a different Michaelis constant, which allows for the expanded dynamic range. We used the engineered Escherichia coli pyrroloquinoline quinone glucose dehydrogenase (PQQGDH) of which His775 was substituted for Asp which showed an increased Km value (25-fold). We first constructed the composite colorimetric analytical system employing the wild-type PQQGDH and His775Asp and evaluated its dynamic range. The composite colorimetric analytical system was constructed and showed a wide dynamic range of 0.5-30 mM with less than +/-5% error. The composite colorimetric analytical system, an extended-range colorimetric analytical system, enabled the determination of the concentration of glucose over a 30-fold range that could not have been achieved using the single colorimetric analytical system. Furthermore, we have demonstrated the composite amperometric glucose sensor employing the combination of His775Asn and His775Asp. The extended-range glucose sensor acquired not only the expanded dynamic range (3-70 mM) that covered both dynamic ranges of the single enzyme sensors but also the narrower substrate specificity of glucose due to the inherited property of engineered enzymes.
Biosensing Techniques↗
New role of glycosaminoglycans on the plasma membrane proposed by their interaction with phosphatidylcholine.
Glycosaminoglycan side chains of membrane proteoglycans have been claimed to be located at the outermost layer of the glycocalyx surrounding the cell. In this study measurements by surface plasmon resonance and solid-phase assay have shown that both chondroitin sulfate and keratan sulfate but not heparin associate with phosphatidylcholine under physiological conditions. Spectrophotometric measurements also showed that chondroitin sulfate restricts the lateral diffusion of phosphatidylcholine in liposomes. These findings indicate that chondroitin sulfate and/or keratan sulfate chains of membrane proteoglycans crouch on the surface of the membrane while heparan sulfate chains stretch outward from the membrane surface as postulated traditionally.
Cell Membrane↗
Distinct roles of two intracellular phospholipase A2s in fatty acid release in the cell death pathway. Proteolytic fragment of type IVA cytosolic phospholipase A2alpha inhibits stimulus-induced arachidonate release, whereas that of type VI Ca2+-independent phospholipase A2 augments spontaneous fatty acid release.
Cytosolic phospholipase A(2)alpha (cPLA(2)alpha; type IVA), an essential initiator of stimulus-dependent arachidonic acid (AA) metabolism, underwent caspase-mediated cleavage at Asp(522) during apoptosis. Although the resultant catalytically inactive N-terminal fragment, cPLA(2)(1-522), was inessential for cell growth and the apoptotic process, it was constitutively associated with cellular membranes and attenuated both the A23187-elicited immediate and the interleukin-1-dependent delayed phases of AA release by several phospholipase A(2)s (PLA(2)s) involved in eicosanoid generation, without affecting spontaneous AA release by PLA(2)s implicated in phospholipid remodeling. Confocal microscopic analysis revealed that cPLA(2)(1-522) was distributed in the nucleus. Pharmacological and transfection studies revealed that Ca(2+)-independent PLA(2) (iPLA(2); type VI), a phospholipid remodeling PLA(2), contributes to the cell death-associated increase in fatty acid release. iPLA(2) was cleaved at Asp(183) by caspase-3 to a truncated enzyme lacking most of the first ankyrin repeat, and this cleavage resulted in increased iPLA(2) functions. iPLA(2) had a significant influence on cell growth or death, according to cell type. Collectively, the caspase-truncated form of cPLA(2)alpha behaves like a naturally occurring dominant-negative molecule for stimulus-induced AA release, rendering apoptotic cells no longer able to produce lipid mediators, whereas the caspase-truncated form of iPLA(2) accelerates phospholipid turnover that may lead to apoptotic membranous changes.
Apoptosis↗
Rat extracorporeal circulation model for evaluation of systemic immunotoxicity.
We have applied a rat extracorporeal circulation (EC) model as an evaluation system for the immunotoxicity of medical devices in contact with the blood stream. Combining popular hemodialysis (HD) membranes [a non-biocompatible membrane, Cupurophane (CUP), and more biocompatible membranes, Cu-ammonium rayon (CAR) and polyacrylonitrile (PAN)] with rat EC, we evaluated the elicitation of acute and delayed immunological responses, as well as the effect of repeated EC. Acute effect markers such as the production of tumor necrosis factor (TNF)-alpha and complement activity during EC, and delayed effect markers such as beta2-microglobulin (beta2-M), IgG, and complement 3 levels, were monitored. Acute markers after EC passage showed responses similar to those previously reported in patients with long-term hemodialysis such as TNF-alpha production and increased complement activity. Although beta2-M and IgG levels increased to 3- to 5-fold of the initial concentration within 4 weeks after rat EC, the trend of IgG increase was inversely correlated with membrane biocompatibility (CUP > CAR = PAN), but this did not occur for elevations in beta2-M (PAN > CAR > CUP). These data suggest that this EC model can reproduce similar immunological responses as seen in HD patients, and can be employed to evaluate medical devices and materials for their delayed, systemic, and repeated exposure effects with respect to immunotoxicity.
Animals↗
Reaction of selenobenzophenones with olefins. Formation of 1H-2-benzoselenopyrans. Reaction of 1H-2-benzoselenopyrans with diazoalkanes
Selenobenzophenone reacts as a diene with dimethyl acetylenedicarboxylate (DMAD) to lead to dimethyl 1H-1-diphenylmethyl-1-phenyl-2-benzoselenopyran-3,4-dicarboxylate (5c) in moderate yield; the initial [4 + 2] cycloaddition is followed by the addition of another 1 mol equiv of selenobenzophenone. The reaction might proceed through carbene insertion of the primary cycloadduct. On the other hand, 4,4'-dimethoxyselenobenzophenone combines as a diene with DMAD furnishing dimethyl 1H-1-p-methoxyphenyl-6-methoxy-2-benzoselenopyran-3,4-dicarboxylate (4a). The reaction of benzoselenopyran derivative (4) with diaryldiazomethanes afforded another type of carbene insertion product.
Journal Article↗
Analysis of HLA-DRB1 alleles in Japanese patients with chronic myelogenous leukemia.
To clarify the association between HLA-DRB1 alleles and chronic myelogenous leukemia (CML), the HLA-DRB1 allele frequencies in 50 Japanese patients each with b2a2 and b3a2 CML and 127 healthy Japanese individuals were examined. In the patients with b2a2 CML, the frequencies of HLA-DRB1*0405, DRB1*08032, and DRB1*1502 were low and that of HLA-DRB1*1201 was high in comparison with the healthy individuals. The frequencies of HLA-DRB1*0403, DRB1*0802, DRB1*1403, and DRB1*1405 were high, and those of HLA-DRB1*08032 and DRB1*1501 were low in the patients with b3a2 CML. The present results suggest positive and negative associations between certain HLA-DRB1 alleles and CML.
Alleles↗
Cardiolipin enhances protein C pathway anticoagulant activity.
The anticoagulant activity of activated protein C (APC) was studied using factor Xa-1-stage assays of both the procoagulant and anticoagulant activities of phospholipid vesicles containing phosphatidylserine or cardiolipin as active phospholipids. In the absence of APC, phosphatidylserine vesicles showed higher procoagulant activity than cardiolipin vesicles whereas cardiolipin vesicles supported APC-dependent anticoagulant activity better than phosphatidylserine vesicles. Enhancement of APC anticoagulant activity in plasma by cardiolipin was markedly stimulated by the APC cofactor protein S. In purified reaction mixtures, cardiolipin in phospholipid vesicles dose-dependently enhanced APC anticoagulant activity. This effect of cardiolipin was partially dependent on protein S, and immunoblotting studies showed that cardiolipin enhanced the APC-mediated cleavage of the factor Va heavy chain at Arg506 and Arg306. In solid-phase binding assays, increasing amounts of cardiolipin in multicomponent phospholipid vesicles increased the affinity for protein S and to a lesser extent APC. These data are consistent with the hypothesis that cardiolipin stimulates the anticoagulant protein C pathway by increasing the affinity of phospholipid surfaces for protein S:APC and by enhancing inactivation of factor Va by APC due to cleavages at Arg506 and Arg306 in factor Va. Based on this, it is further hypothesized that anti-cardiolipin or anti-oxidized cardiolipin antibodies may be thrombogenic because they inhibit phospholipid-dependent expression of the anticoagulant protein C pathway.
Blood Coagulation↗
Early diagnosis of postoperative infection: assessment of whole blood chemiluminescence.
Whole blood chemiluminescence (CL), which allows for the evaluation of both the oxygen radical release by phagocytes and the serum opsonin activity using very small amounts of blood, is considered to be a useful means of assessing the host defense against infection. We measured the whole blood chemiluminescence in 59 patients before and after open surgery (surgery by a laparotomy) for gastrointestinal disease. Early postoperative infection was detected in 12 (20.3%) of the 59 patients. These 12 patients all had significantly higher white blood cell counts compared with the noninfected patients on the third and subsequent days after surgery (P < 0.01). The peak CL in the early postoperative infected group was also significantly higher than that in the noninfected group on the day of surgery (P < 0.0001), 1 day after surgery (P < 0.0001), and 3 days after surgery (P < 0.01). Whole blood CL may therefore be a useful modality for the early detection of postoperative infection in the future.
Adult↗
Significant changes in the serum levels of IL-6, h-HGF, and type IV collagen 7S during the perioperative period of a hepatectomy: relevance to SIRS.
We analyzed the changes in the serum levels of both interleukin-6 (IL-6), human hepatocyte growth factor (h-HGF), and type IV collagen 7S (7S) during the perioperative period of a hepatectomy and evaluated their relationship with systemic inflammatory response syndrome (SIRS). The study subjects consisted of 40 patients who underwent a hepatectomy. In 14 out of 40 patients, postoperative SIRS(+) was observed. Between the SIRS(+) and SIRS(-) cases, there were significant differences in the preoperative values of prothrombin time, hepaplastin test, cholinesterase, and indocyanine green retention at 15 min (P < 0.01). Compared with the SIRS(-) cases, the IL-6, h-HGF, and 7S of the SIRS(+) cases fluctuated in a higher range and remained significantly higher after postoperative day 1 (P < 0.05). Eight out of 14 SIRS(+) patients had postoperative complications. In the 8 SIRS(+) patients with postoperative complications and in the 4 patients in which the SIRS(+) state lasted 3 days or longer, the 7S levels were significantly higher during the perioperative period (P < 0.05). In the SIRS(+) cases, the postoperative levels of IL-6 and h-HGF, as well as pre- and postoperative levels of 7S, were elevated. We therefore consider these levels to be risk factors for complications during the perioperative period of a hepatectomy.
Collagen↗
Hepatic resection using the harmonic scalpel.
We describe herein our technique of performing extensive resection of the liver by blunt dissection in combination with excision using a harmonic scalpel. A ball coagulator was inserted at 3-cm intervals along the proposed cutting line in the liver, and the liver parenchyma between these holes was then cut using coagulation shears. Regardless of the condition of the liver, good coagulation and cutting were achieved using the harmonic scalpel without vascular occlusion when dividing the shallow layer of the liver, and no complications in association with the harmonic scalpel, such as postoperative bleeding, bile leakage, or abscess formation at the cut margins, occurred. In the deep layer below the main trunk of the hepatic vein, blunt dissection was used, since it was difficult to achieve sufficient control of bleeding from large vessels using the harmonic scalpel alone. Therefore, when used in combination with other techniques, the harmonic scalpel appears to be an effective device for liver surgery that minimizes bleeding and decreases the vascular clamping time.
Adult↗