ST segment elevation in the precordial leads mimicking Brugada syndrome.
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Arrhythmias, Cardiac↗
Biomedical subjects
T Kurata
Publications and source records attributed to T Kurata.
Suppression of specific IgE antibody responses by liposome-conjugated ovalbumin in mice sensitized with ovalbumin via the respiratory tract.
BACKGROUND: Previously we have shown that intranasal administration of ovalbumin (OVA) together with cholera toxin (CT) abrogates nasal tolerance to OVA, resulting in the induction of specific IgE antibody (Ab) responses, and that intraperitoneal injection of OVA coupled with liposomes (OVA-liposomes) induces a selective suppression of IgE Ab responses to OVA. Whether OVA-liposomes suppress anti-OVA IgE Ab responses in mice sensitized with CT-combined OVA via the respiratory tract remains to be clarified. METHODS: In some experiments, mice were given OVA, liposomes or OVA-liposomes with or without CT intranasally three times, at 2-week intervals (weeks 0, 2 and 4). In other experiments, mice were given OVA-liposomes intranasally 2 days before or 1 and 3 weeks after CT-combined OVA (week 0), which was administered intranasally three times, at 2-week intervals (weeks 0, 2 and 4). Two weeks after the third administration of CT-combined OVA (week 0), nasal wash and serum IgA, IgG and IgE Ab responses were assayed. RESULTS: Pretreatment with OVA-liposomes suppressed IgE Ab responses to CT-combined OVA, with a significantly high production of both nasal IgA and serum IgG Abs. Moreover, treatment with OVA-liposomes 1 and 3 weeks after CT-combined OVA administration also suppressed IgE Ab responses. The suppression of anti-OVA IgE Ab production by OVA-liposomes was accompanied by a simultaneous enhancement of specific IgA and IgG (IgG1, and especially IgG2a) Ab production. CONCLUSIONS: Postimmunization treatment with OVA-liposomes, as well as preimmunization treatment, suppressed specific IgE Ab responses in mice sensitized intranasally with CT-combined OVA. Allergens conjugated to liposomes may be appropriate for preventing the development of allergies to inhaled or dietary antigens in humans.
Administration, Intranasal↗
Phase I and pharmacokinetic study of a new taxoid, RPR 109881A, given as a 1-hour intravenous infusion in patients with advanced solid tumors.
PURPOSE: RPR 109881A is a new semisynthetic taxoid compound that has a similar mechanism of action to docetaxel. The purpose of this phase I study was to characterize the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetic profile, and antitumor effects of this agent. PATIENTS AND METHODS: Nineteen eligible patients with advanced solid tumors were enrolled. RPR 109881A was administered as a 1-hour intravenous infusion every 3 weeks at doses ranging from 15 to 75 mg/m(2). Pharmacokinetic evaluation was performed at the first cycle. RESULTS: Neutropenia (febrile neutropenia) and fatigue were dose-limiting toxicities at doses of 60 and 75 mg/m(2) and seemed to be dose-related. Both thrombocytopenia and anemia were infrequent. Nonhematologic toxicities were generally mild. Pharmacokinetic studies indicated that RPR 109881A plasma disposition was bi- or triphasic, with a high total plasma clearance, a large volume of distribution, and a long terminal half-life. The area under the concentration-time curve (AUC) and the peak concentration of RPR 109881A seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics. Urinary excretion over 48 hours was low, with a mean of 0.8 +/- 0.36% of the administered dose. A significant relationship existed between the percentage decrease of neutrophil counts and the AUC of RPR 109881A. Among 18 assessable patients, two partial and two minor responses were documented. CONCLUSION: RPR 109881A was found to be a well-tolerated and promising taxoid agent. The MTD was 75 mg/m(2), and the recommended dose for phase II study was 60 mg/m(2) as a 1-hour infusion every 3 weeks.
Adult↗
Chemical characteristics of dehydro-L-ascorbic acid.
Dehydro-L-ascorbic acid (DAA) exists mainly in its C2 hydrated bicyclic form (5) in an aqueous solution, and monocyclic DAA (3), which is the expected reaction product immediately after the oxidation of AA, has not been observed by NMR spectroscopy. The formation mechanism for 5 from 3 and the stability of 5 were examined by the semi-empirical molecular orbital method (MOPAC). It was indicated that the protonation reaction was the key step in the formation of 5, therefore, the formation of 5 is thought to be more difficult under physiological conditions which mostly involve in the neutral or slightly alkaline state. However, by NMR, it was confirmed that, even in a neutral or slightly alkaline state very close to physiological conditions, the predominant form of DAA existing in an aqueous solution immediately after the enzymatic oxidation of AA was confirmed to be 5, although the possible existence of other forms of DAA at very low concentrations could not be completely excluded.
Dehydroascorbic Acid↗
Interconversion between dehydro-L-ascorbic acid and L-ascorbic acid.
L-Ascorbic acid (AA) plays an important role in biological systems as an electron donor. Erythorbic acid (EA) is the epimer of AA and has chemical characteristics very similar to those of AA. It is demonstrated in the present study by 1H-NMR that dehydro-L-ascorbic acid (DAA) was reduced by EA under neutral conditions but not acidic, and that dehydroerythorbic acid (DEA) was also reduced by AA under the same conditions. These reactions also occurred at a low concentration close to the concentration of AA in such biological tissue as the liver. Furthermore, the interconversion of DAA and AA at neutral pH and low concentration was also confirmed by radioluminography. These results suggest the interconversion between DAA and AA in vivo.
Ascorbic Acid↗
Dihydropyrimidine dehydrogenase activity in human pancreatic tumor tissues.
Dihydropyrimidine dehydrogenase (DPD) activity was investigated using pancreatic tumors and normal pancreatic tissues surrounding the tumors obtained from 12 patients with pancreatic cancer. The mean DPD activity (+/- SD) was 2.69 +/- 1.88 nmol/mg protein/hr in normal pancreatic tissue and was 6.59 +/- 5.36 nmol/mg protein/hr in pancreatic tumor tissues. The DPD activity in tumor tissue was two- to threefold higher (p < 0.01) than that in normal tissue, but no marked difference was observed in DPD activity among cancer stages. The DPD activity of pancreatic tumors may be a useful clinical marker of the responsibility of fluorinated pyrimidine dosing in pancreatic cancer.
Adult↗
Time-dependent changes of tissue erythorbic acid concentrations in guinea pigs.
The concentrations of erythorbic acid(ErA) and L-ascorbic acid(AsA) in the tissues of guinea pigs orally administered AsA or ErA were measured over the passage of time using high-performance liquid chromatography. Guinea pigs were each administered 5 mg AsA or 100 mg ErA, and killed at a specified time thereafter. The AsA concentrations in the tissues of AsA-administered guinea pigs and the ErA concentrations in the tissues of ErA-administered guinea pigs increased for 3 h after the respective administrations and decreased thereafter in both groups. The AsA concentration in the tissues of AsA-administered guinea pigs tended to be similar to the sum of AsA and ErA concentrations in the ErA-administered guinea pigs within 3 h after administration.
Adrenal Glands↗
Long-term results of percutaneous transluminal angioplasty for hemodialysis shunt insufficiency
Purpose: The purpose of this study was to evaluate the long-term results of percutaneous transluminal angioplasty (PTA) for stenosis and/or occlusion of dialysis shunts. Methods: One hundred thirty-nine stenosed or thrombosed dialysis shunts (99 native fistulae, 37 grafts) in 122 patients were treated by PTA. In 39 cases, additional PTA for restenosis was performed. In total, 230 PTAs were performed (1-10 PTA/shunt). Results: The initial success rate was 86% in cases without occlusion. In contrast, the success rate in cases with occlusion was 53%, significantly worse than in the cases without occlusion. In cases in which initial success was obtained, primary cumulative patency rates at 3, 6, and 12 months were 87%, 60%, and 40%, respectively. With repeat PTA, secondary cumulative patency rates at 3, 6, 12, and 24 months were 96%, 83%, 63%, and 55%, respectively. Patency of native fistulae was better than patency of grafts. There was no significant relationship between the anatomical location of the stenoses and the patency rates. Conclusion: PTA is an effective treatment for shunt stenosis; although primary patency after PTA is not sufficient, repeated PTA increases patency.
Journal Article↗
[Metallic stent placement for iliac artery occlusive disease].
Since 1991, we have performed stent placement for 35 iliac artery lesions in 31 patients. The etiologic diseases were atherosclerotic in 34 patients and traumatic dissection in one. The indications of placement were total occlusion in 3, late restenosis after angioplasty in 5, dissection in 5, and residual stenosis due to inadequate angioplasty in 21. We also performed direct stent placement for one traumatic dissection. The stents used were Wallstents in 10, Palmaz stents in 14, Strecker stents in 9, and Memotherm stents in 2 lesions. Follow-up was performed clinically or angiographically with measurement of the ankle/arm pressure index. Stent placement was successful in all cases, and relief or improvement of symptoms was achieved. The follow-up period ranged from 6-85 months (mean, 37.3 months). Late stent stenosis or occlusion occurred in 6 cases, among which 4 occluded lesions were successfully recanalized by thrombolytic therapy with angioplasty or second stent placement. In total, the primary patency rates were 88% and 77% at two and four years, respectively, while the secondary patency rates were 94% and 94%. In conclusion, metallic stent placement may offer extended application of intravascular treatment for iliac artery occlusive disease, and good long-term patency rates can be expected.
Adult↗
[Typing of herpes simplex virus in patients with uveitis].
AIM: To examine the type of herpes simplex virus (HSV) in cases with uveitis. MATERIALS AND METHODS: Intraocular fluid specimens obtained from 3 cases with herpetic iridocyclitis and 6 cases with acute retinal necrosis (ARN) were examined by polymerase chain reaction (PCR). HSV typing was performed by the restriction patterns of the PCR products. Serum samples obtained from these cases and 33 cases with uveitis were examined by neutralization test (NT) for the availability of the typing of HSV. RESULTS: The restriction patterns of the PCR products amplified from 3 specimens of iridocyclitis revealed HSV type 1 DNA. HSV type 2 DNA was identified in 5 of 6 cases of ARN and HSV type 1 DNA was found in only one case. The results of serum NT titers correlated with the typing of the amplicons. CONCLUSIONS: In the cases studied, HSV type 1 was the dominant etiological agent in herpetic iridocyclitis, while HSV type 2 played a similar role in HSV-associated ARN. The examination of the serum NT may be helpful for the identification of the etiological types of HSV in patients with uveitis.
Adult↗
A proposal for safety standards for human use of cholera toxin (or Escherichia coli heat-labile enterotoxin) derivatives as an adjuvant of nasal inactivated influenza vaccine.
Cholera toxin (CT) and Escherichia coli heat-labile toxin (LT) are not only the causative agents of diarrhea but are also strong mucosal adjuvants which enhance immune responses to mucosally coadministered bystander antigens. One of the most promising applications of these toxins would be as mucosal adjuvant of nasal influenza vaccine. In comparison to current inactivated vaccines, the nasal vaccine provides superior cross-protection by inducing production of cross-reacting anti-viral IgA antibodies in the respiratory tract even when the vaccine strain is different from the epidemic strain. On the use of the toxins as mucosal adjuvants in humans, toxicity and allergenicity of the toxins are problems which impinge on safety. To resolve these problems, various approaches have been attempted to produce less toxic and less allergenic CT (or LT) derivatives. We now propose the following standards for human use of safer CT (or LT) derivatives as an adjuvant of a nasal influenza vaccine. Thus, CT (or LT) derivatives can be administered intranasally together with a current inactivated influenza vaccine, provided they meet the following criteria. 1) A single dose of the derivatives, administered intranasally by spraying, should be around 100 Eg/adult in a volume of less than 0.5 ml. 2) CT (or LT) derivatives should retain the properties of the native CT (or LT), i. e., the ability to augment secretory IgA and serum IgG Ab responses to viral surface glycoproteins, when administered intranasally together with an inactivated influenza vaccine. 3) CT (or LT) derivatives should not induce IgE Ab responses to the vaccine, as well as to the CT (or LT) itself. 4) The CT (or LT) should be nontoxic; the toxicity of the derivatives, as determined by the Y-1 adrenal cell assay, should not exceed 1/100 EC(50) of the native CT (or 1/1000 ECi of the native CT). 5) CT (or LT) derivatives should not cause serious disease in guinea pigs when administered intranasally or intraperitoneally at the dose used in humans (around 100 Eg).
Adjuvants, Immunologic↗
[A proposal of essentials for forensic pathological diagnosis of sudden infant death syndrome (SIDS)].
There are many sudden unexpected infant death cases which are easily diagnosed as sudden infant death syndrome (SIDS) both with or without autopsy in Japan. A SIDS diagnosis may provide a cover for accidental or criminal death. SIDS should not be a convenient diagnostic box that shelters the cases of unexpected infant death which lack the necessary antemortem information to make the correct diagnosis. The authors consider that SIDS should be diagnosed according to the direction of the international definition of SIDS, and propose the following essentials for a forensic pathological diagnosis. 1) A thorough autopsy should be performed based on precise autopsy protocol, including not only histological observation, but also, if necessary, toxicological, bacteriological, viral and/or biochemical examinations. 2) The forensic pathologist should be provided with pertinent information regarding antemortem health status, past clinical history, social circumstances, death scene investigation, etc. In order to collect more precise information, the authors recommend using a questionnaire such as the example in this report to record information from the deceased's guardians. 3) Suspicion of accidental death or infanticide should be completely ruled out. SIDS should be diagnosed only after these three essentials have been satisfied. When there is even a slight suspicion of accidental death or infanticide, or when the forensic pathologist can not obtain pertinent information about the deceased, the causes and classification of the death should be diagnosed as unspecified or undetermined. That is, the causes and classification of the death are undetermined as to whether it is a natural or unnatural death. Furthermore, several warning flags indicating a possible SIDS diagnosis were proposed: a case found dead in a supine position, the existence of a foreign body in the respiratory tract or mild infectious findings. The authors also emphasize the physician's responsibility to report a case found dead or dying of unnatural or clinically unexplained causes to the police. This is the crucial first step in getting an accurate diagnosis of SIDS.
Autopsy↗
Identification of effective constituents of influenza vaccine by immunization with plasmid DNAs encoding viral proteins.
The use of plasmid DNA encoding influenza viral proteins to vaccinate animals constitutes a promising approach to the development of effective subunit vaccines. This review describes the results obtained by the immunization of mice with such plasmid DNAs. (i) Both hemagglutinin (HA)- and neuraminidase (NA)-expressing DNAs for the surface glycoproteins from A/PR/8/34 (H1N1) or B/Ibaraki/2/85 virus can provide the most effective protection against influenza A-type or B-type virus infection among the various viral protein-expressing DNAs tested in BALB/c mice. (ii) A mixture of plasmid DNAs encoding HA and NA can provide more effective protection against virus challenge than plasmid DNA encoding HA or NA alone in BALB/c mice. (iii) NA-DNA can provide protection against infection not only by homologous virus but also by drift viruses. (iv) HA-DNA from A/PR/8/34 (H1N1) virus provides significant protection only in BALB/c (H-2(b)) mice, whereas HA-DNA from B/Ibaraki/2/85 virus affords significant protection in BALB/c, B10 (H-2(d)), and C3H (H-2(k)) mice. NA-DNA from both A-type and B-type viruses provides significant protection in the three strains of mice. These results suggest that both HA and NA molecules should be used as vaccine components to provide effective protection against influenza A-type and B-type virus infection in genetically heterogeneous humans.
Animals↗
Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins.
Human DOCK180, which was originally identified as a major protein bound to the Crk oncogene product, is an archetype of the CDM family of proteins, including Ced-5 of Caenorhabditis elegans and Mbc of Drosophila melanogaster. After DOCK180, at least three putative human proteins that manifest high amino acid sequence similarity to DOCK180 have been registered in the GenBank/EMBL database. We have designated one of them, KIAA0209, as DOCK2 and characterize here. DOCK2 mRNA was expressed mostly in peripheral blood cells, followed by slight expression in the spleen and thymus, whereas DOCK180 was expressed in all tissues tested except in peripheral blood cells. Immunostaining of human cadaver tissues revealed that the expression of DOCK2 was limited to the lymphocytes and macrophages of various organs. DOCK2 bound to and activated Rac1, as did DOCK180; however, DOCK2 did not bind to CrkII, which transduces signals at focal adhesions. Thus, DOCK180 and DOCK2 are regulators of Rac and function in adherent and non-adherent cells, respectively.
Amino Acid Sequence↗
[Class 1 infections: 1) Viral diseases].
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Hemorrhagic Fevers, Viral↗
An infectious DNA clone of HIV type 1 subtype C.
Among the 10 subtypes of the M group of human immunodeficiency virus type 1, subtype C is the most prevalent in India and may dominate worldwide in the near future; however, there has been no report on the infectious DNA clone of this subtype. We have isolated an infectious DNA clone of the 93IN101 strain of HIV-1 subtype C, which was isolated in India in 1993. MAGIC5 cells, which are derived from HeLa-CD4-LTR-beta-gal (MAGI) cells and express CCR5, were inoculated with the 93IN101 strain of HIV-1 subtype C. The genomic DNA of the infected cells was used as a template for amplification of the HIV-1 genome. The genome DNA obtained was subcloned into pBR322, and the resulting plasmid was designated as pIndie-C1. The insert of pIndie-C1 was 9680 bp in length and had an intact genomic organization with open reading frames of all structural, regulatory, and accessory proteins. Phylogenetic analysis confirmed that the nucleotide sequence of pIndie-C1 is closely related to those of HIV-1 subtype C isolated in India. Transfection of pIndie-C1 into 293T cells yielded as much virus as did pNL432, one of the most widely used HIV DNA clones. The recovered Indie-C1 virus infected MAGIC5 but not the parent MAGI cells, indicating that Indie-C1 is CCR5 tropic. Expressed Env protein was reacted efficiently with the sera of HIV-1-infected patients of India, but not of Japan. Expression of Nef and Vpr was also confirmed by immunoblotting.
Gene Products, env↗
[Conservative therapy of acute coronary syndrome in its acute phase and preventive measures].
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Acute-Phase Reaction↗
Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(i)
Many receptors for neuropeptides and hormones are coupled with the heterotrimeric G(i) protein, which activates the p42/44 mitogen-activated protein kinase (ERK/MAPK) cascade through both the alpha- and betagamma-subunits of G(i). The betagamma-subunit activates the ERK/MAPK cascade through tyrosine kinase. Constitutively active G(alpha)i2 (gip2) isolated from adrenal and ovarian tumours transforms Rat-1 fibroblasts and also activates the ERK/MAPK cascade by an unknown mechanism. The ERK/MAPK pathway is activated by Ras, and is inhibited when the low-molecular-mass GTP-binding protein Rap1 antagonizes Ras function. Here we show that a novel isoform of Rapl GTPase-activating protein, called rap1GAPII, binds specifically to the alpha-subunits of the G(i) family of heterotrimeric G-proteins. Stimulation of the G(i)-coupled m2-muscarinic receptor translocates rap1GAPII from the cytosol to the membrane and decreases the amount of GTP-bound Rap1. This decrease in GTP-bound Rap1 activates ERK/MAPK. Thus, the alpha-subunit of G(i) activates the Ras-ERK/MAPK mitogenic pathway by membrane recruitment of rap1GAPII and reduction of GTP-bound Rap1.
3T3 Cells↗