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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 1,009 records · Page 56Linked to original sources

[Laryngeal fractures due presumably to tracheal intubation in resuscitation].

In three autopsy cases performed in our department, we observed the throat-skeleton fractures occurring presumably during the tracheal intubation in resuscitation. Case 1. 63-year-old man died of acute hemorrhagic pancreatitis shortly after the quarrel with a suspected person. The autopsy examination showed the fractured hyoid bone with haemorrhage at the fracture site. The question whether direct pressure on his neck by the suspected person results the fracture of the hyoid bone was investigated. Case 2. 75-year-old man treated for senile dementia was clubbed with a walking stick by the other patient treated for same disease and he died of traumatic shock. The fracture of the hyoid bone was also noted like case 1. The strike in the throat and/or the neck compression by the assailant were suspected of being the cause of this fracture. Case 3. 47-year-old man got the severe head injury during the quarrel. He died about two weeks after operation and the cause of death was multiple organ failure. The autopsy findings revealed the fracture of the superior thyroid horn. The neck compression by the suspected person was the questionable cause of this fracture. In all these cases, the asphyxia findings and the signs of the direct pressure on the neck by the assailants were not recognized other than the above-mentioned laryngeal fractures. From the autopsy findings, together with the criminal investigation, we consider collectively that the tracheal intubation in resuscitation induced presumably these laryngeal injuries. In general, throat-skeleton fractures seem to be the signs of homicidal violence against the neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case of gold-induced pneumonitis showing a positive reaction in the drug lymphocyte stimulation test (DLST) for gold].

A case of acute interstitial pneumonia developing during gold therapy is reported. A 67-year-old female with rheumatoid arthritis for about twenty years who received a total dose of 80 mg of gold thiomalate (Shiosol) for about two months, developed high fever and dry cough. Exertional dyspnea developed and chest roentgenogram showed diffuse small nodular and reticular shadows. RA and RAPA tests were positive. Drug lymphocyte stimulation test (DLST) for Shiosol was positive. The dyspnea resolved on administration of methylprednisolone. Chest roentgenogram and CT-scan showed improvement. A total dose of 80 mg of gold thiomalate, as administered in this case, is the minimum dose previously reported in Japan. It has been recently reported that allergic reaction is the mechanism of gold lung. In the present case, positive DLST indicated the existence of many activated lymphocytes, and was very useful in the diagnosis of gold lung.

Aged↗

Molecular cloning of the ViaB region of Salmonella typhi.

The ViaB region required for Vi antigen production in Salmonella typhi was cloned. The plasmid pGBM124 containing a 14-kb S. typhi chromosomal DNA fragment conferred the ability to produce Vi antigen on Escherichia coli HB101 and ViaB-deleted S. typhi GIFU10007-3. Tn5 insertion analysis showed that the 14-kb DNA was split into three regions. Region 1 and region 2 are involved in the biosynthesis of Vi polysaccharide. Region 3 is involved in translocation of the Vi polysaccharide to the cell surface. Southern blot hybridization showed that regions 2 and 3 but not region 1, were considerably homologous to the DNA of Vi-positive Citrobacter freundii.

Antigens, Bacterial↗

Potent and preferential inhibition of Ca2+/calmodulin-dependent protein kinase II by K252a and its derivative, KT5926.

Effects of protein kinase inhibitors, K252a and its derivative KT5926, on Ca2+/calmodulin-dependent protein kinase II were examined. Both compounds potently inhibited Ca2+/calmodulin-dependent protein kinase II. Kinetic analyses indicated that the inhibitory effect of K252a and KT5926 was competitive with respect to ATP (Ki: 1.8 and 4.4 nM, respectively) and noncompetitive with respect to the substrates. Taken together with a previous report (Nakanishi et al. Mol. Pharmacol. 37, 482, 1990) concerning the Ki values of these compounds for ATP with various protein kinases, the results suggest that K252a and KT5926 are potent and preferential inhibitors of Ca2+/calmodulin-dependent protein kinase II.

Alkaloids↗

Fluorescent probes for retinoic acid receptors: molecular measures for the ligand binding pocket.

Two fluorescent probes for nuclear retinoic acid receptors (RARs) have been developed, both containing a biologically active retinoid moiety and a fluorescent dansyl moiety, but differing in the length of the spacer arm connecting the two moieties. Both probes bind RARs at their retinoid-binding sites, revealing the usefulness of the compounds as fluorescent RAR probes. By measuring the specific increase of the probes' fluorescence intensity caused by the binding to RARs, the linearized length of the RAR's retinoid-binding pocket could be estimated.

Binding, Competitive↗

Renal and hepatic microsomal enzymes responsible for bioactivation of 3-methoxy-4-aminoazobenzene in the rodent.

Activities of the renal and hepatic microsomal enzymes responsible for the N-hydroxylation and mutagenic activation of 3-methoxy-4-aminoazobenzene (3-MeO-AAB) were examined in male mice, rats, hamsters and guinea pigs. In all these rodent species, hepatic microsomes showed definite N-hydroxylation of 3-MeO-AAB, whereas the renal activity was detected only in mice. The hepatic enzyme responsible for N-hydroxylation of 3-MeO-AAB (3-MeO-AAB N-hydroxylase) was induced in all species except mice by phenobarbital and selectively in mice and hamsters by 3-methylcholanthrene, whereas these cytochrome P450 inducers did not affect the renal enzyme in mice, rats or hamsters. In individual microsome samples, activities for N-hydroxylation and mutagenic activation of 3-MeO-AAB correlated well. These results indicate that the renal and hepatic enzymes responsible for the metabolic activation of 3-MeO-AAB differed among different species of rodent animals in terms of their activity and inducibility with cytochrome P450 inducers.

Animals↗

Surface expression of a T cell receptor beta (TCR-beta) chain in the absence of TCR-alpha, -delta, and -gamma proteins.

The antigen receptor expressed by mature T cells has been described as a disulfide-linked alpha/beta or gamma/delta heterodimer noncovalently associated with CD3, a complex of transmembrane proteins that communicates signals from the T cell receptor (TCR) to the cell interior. Studies suggest that all component chains must assemble intracellularly before surface expression can be achieved. We described, however, a CD4+/CD8+ transformed murine thymocyte, KKF, that expresses surface TCR-beta chains in the absence of gamma, delta, and alpha proteins; these beta chains are only weakly associated with CD3-epsilon and CD3-zeta. Furthermore, KKF responds differently to stimulation through TCR-beta and CD3-epsilon, a functional dissociation that has been ascribed to a CD4+/CD8+ subpopulation of normal thymocytes. KKF's unique TCR structure may offer an explanation for the functional anomalies observed.

Animals↗

Different effects of DNA adducts induced by carcinogenic and noncarcinogenic azo dyes on in vitro DNA synthesis.

M13mp10 phage DNA modified with the carcinogen 3-methoxy-4-aminoazobenzene (3-MeO-AAB) or the noncarcinogen 2-methoxy-4-aminoazobenzene (2-MeO-AAB) was used as a template for E.coli DNA polymerase I. Analysis of the reaction products on DNA sequencing gels showed that with both types of compound the induced lesions blocked DNA synthesis, mainly at one base prior to guanine adducts, but that the inhibition by 3-MeO-AAB-adducts was substantially greater than that by 2-MeO-AAB-adducts. Thus different effects on DNA replication between 3-MeO-AAB- and 2-MeO-AAB-adducts might be a reflection of differences in their carcinogenic potency.

Bacteriophages↗

Fluorescent and photoaffinity labeling probes for retinoic acid receptors.

A fluorescent probe for retinoid receptors (RARs) was designed and prepared. The probe consists of a retinoid moiety and a dansyl moiety, i.e., 2-[3-(5-dimethylaminonaphthalene-1-sulfonyl)- aminopropyl-1-oxy]-4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carboxamido]benzoic acid: DAM-3. DAM-3 specifically bound RARs. Additionally, a photoreactive RAR fluorescent probe was designed and prepared, i.e., 2-[3-(5-azidonaphthalene- 1-sulfonyl)aminopropyl-1-oxy]-4-[(5,6,7,8-tetrahydro-5,5,8,8- tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (ADAM-3). ADAM-3 irreversibly and specifically bound RARs using ultraviolet irradiation.

Affinity Labels↗

Fluorescent and photoaffinity labeling derivatives of rhizoxin.

A fluorescent probe (D-RZX) and a photoreactive fluorescent probe (AD-RZX) for studying the rhizoxin binding site on tubulin were prepared by the derivatization of rhizoxin (RZX). D-RZX consists of a rhizoxin moiety and a dansyl moiety. AD-RZX has a 5-azidonaphthalene-1-sulfonyl moiety instead of the dansyl moiety of D-RZX. Both D-RZX and AD-RZX bound tubulin in a mutually competitive manner with rhizoxin, indicating their binding to the rhizoxin site on tubulin. AD-RZX bound the rhizoxin site covalently after UV-irradiation, thus showing its usefulness as a photo-affinity probe for labeling of the rhizoxin site.

Affinity Labels↗

32P-postlabeling analysis of DNA adducts in rat livers after treatment with genotoxic and non-genotoxic 4-aminoazobenzene derivatives.

Formation of hepatic DNA adducts was studied in rats following intraperitoneal administration of a hepatocarcinogen, 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and a non-hepatocarcinogen, 2-methoxy-4-aminoazobenzene (2-MeO-AAB). The 32P-post-labeling assay revealed 3-MeO-AAB to give more than 20-fold higher amounts of DNA adducts than did 2-MeO-AAB. Furthermore, five adducts, one of which accounted for over 70% of the total modified bases, were found in DNA from 3-MeO-AAB-treated rats, whereas only one adduct was apparent in 2-MeO-AAB-treated DNA. Our data thus suggested that the difference in hepatocarcinogenic activity between 3-MeO-AAB and 2-MeO-AAB might be, at least in part, dependent on quantitative and qualitative differences in their azo dye-DNA adduct formation in the rat liver.

Animals↗

Thallium-201 stress scintigraphy in Takayasu arteritis.

Thirty-eight women with Takayasu arteritis were studied using thallium-201 stress myocardial scintigraphy to assess the prevalence and pathophysiology of the perfusion abnormality. Twenty (53%) had abnormal scintigraphic findings (group A). Abnormal scans were divided into 3 groups: permanent defects in 6, reversible defects in 7 and slow washout in 7. The remaining 18 patients had normal scintigrams (group N). Group A had a tendency to be older and to have a high prevalence of complicated significant aortic regurgitation. Interventricular thickness plus left ventricular posterior wall thickness (26 +/- 7 vs 17 +/- 2 mm, p less than 0.01) and left ventricular mass (267 +/- 121 vs 133 +/- 39 g, p less than 0.01) were all greater in group A on echocardiography. The mean value of the central aortic pressure in systole was 170 +/- 15 mm Hg in the 7 catheterized patients in group A. Coronary ostial stenoses were present in 2 group A patients who showed reversible defects on scintigrams. These data indicate that the abnormal perfusion detected by imaging in patients with Takayasu arteritis was responsible for a decrease in coronary reserve or myocardial damage, or both, due to long-standing systemic hypertension or aortic regurgitation. Coronary artery disease should be considered if a reversible defect is present.

Adult↗

Cloning and characterization of an amidase gene from Rhodococcus species N-774 and its expression in Escherichia coli.

For investigation of an unknown open reading frame which is present upstream of the nitrile hydratase (NHase) gene from Rhodococcus sp. N-774, a longer DNA fragment covering the entire gene was cloned in Escherichia coli. Nucleotide sequencing and detailed subcloning experiments predicted a single open reading frame consisting of 521 amino acid residues of Mr 54,671. The amino acid sequence, especially its NH2-terminal portion, showed significant homology with those of indoleacetamide hydrolases from Pseudomonas savastanoi and Agrobacterium tumefaciens, and acetamidase from Aspergillus nidulans. The 521-amino acid coding region was therefore expressed by use of the E. coli lac promoter in E. coli, and was found to direct a considerable amidase activity. This amidase hydrolyzed propionamide efficiently, and also hydrolyzed, at a lower efficiency, acetamide, acrylamide and indoleacetamide. These data clearly show that the unknown open reading frame present upstream of the NHase coding region encodes an amidase. Because the TAG translational stop codon of the amidase is located only 75 base pairs apart from the ATG start codon of the alpha-subunit of NHase, these genes are probably translated in a polycistronic manner.

Amidohydrolases↗

Induction of putative new cytochrome P450 isozyme in rat liver by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Changes in hepatic enzymes responsible for mutagenic activation of food mutagens-carcinogens by treatment with 2-amino-1-methyl-6-phenylimidazo [4, 5-b]pyridine (PhIP) in male F344 rats were examined using the Salmonella mutation test, with 3 heterocyclic aromatic amines as substrates, and further characterized by Western blot analysis with anti-P450 monoclonal antibodies (MoAbs) against rat P450IA1 and P450IA2. Enzymatical and immunochemical analyses indicated that PhIP could induce a putative new P450 isozyme, mol. wt., 51,000, together with P450IA1 and P450IA2 in rat liver microsomes. The profiles of induced P450 molecular species varied dramatically, depending on the time after PhIP administration.

Animals↗

Novel effect of cyclicization of the Arg-Gly-Asp-containing peptide on vitronectin binding to platelets.

Vitronectin is one of the glycoproteins that mediate cell adhesion and spreading of a variety of cells through the RGD(S) sequence. Vitronectin is demonstrated to bind to glycoprotein IIb-IIIa and play a role in platelet aggregation. Synthetic peptides containing the RGD(S) sequence can inhibit vitronectin binding to platelets, but the affinity of these peptides is less than 1/100th that of native vitronectin. The present study thus examined the ability of modified RGD(S)-containing peptide to inhibit vitronectin binding to thrombin-stimulated platelets. The cyclicization of GRGDSPA peptide was done by the linkage of NH2-terminal glycin and the COOH-terminal alanin. The circular dichroism spectrum of cyclic GRGDSPA peptide only showed negative minimum at approximately 220 nm, but those of other linear peptides such as GRGDSPA and GRGESPA had no effect. This result indicated that only the cyclic GRGDSPA peptide retained some conformational structure to restrict its flexibility. Inhibition experiments revealed that the affinities of the ligands for the receptor decreased in the order of vitronectin = fibronectin = fibrinogen = von Willebrand factor (vWF) greater than cyclic GRGDSPA peptide greater than GRGDSPA peptide. GRGESPA peptide had no effect. These results demonstrate that the conformational structure of the RGD(S) sequence plays the important role for the affinity of vitronectin binding to activated platelets and the increased affinity of the modified peptide is a prerequisite for the potential antithrombotic use.

Amino Acid Sequence↗

A simulation study comparing designs for dose ranging.

Only with knowledge of the (prior) distribution of dose-response parameters in a population, can one determine both the initial dose of a drug for chronic administration to an individual (such as the dose producing a fixed degree of response in a fixed proportion of the population) and an appropriate subsequent (adjusted) dose (such as the dose yielding a desirable response according to the posterior parameter distribution, given an observed response to an initial dose). The currently FDA-sanctioned design for a dose-ranging study, the parallel-dose design, assigns just one of several doses to each patient. It does not provide good information on the distribution of individual dose-response parameters. A cross-over design assigns several dose levels to each patient. It therefore can provide better information, but does not resemble clinical practice. Consequently, study participants must be restricted to patients who can tolerate such non-therapeutic drug exposure, posing problems in extrapolation of study results to other types of patients. A titration or dose-escalation design begins all patients on placebo and, except for those patients assigned to a placebo-only group, escalates the dose for a patient at preset intervals only when clinical response at lower doses is inadequate. It both exposes patients to several dose levels and resembles good clinical practice, allowing study of a representative patient sample. We report here the simulation results of parameter estimation for the three designs when the data arise from complex and realistic dose-response models and/or with certain complications in study execution. The dose-escalation design clearly performs better overall than the parallel-dose design for the models considered here, and generally, just a little worse than the cross-over design. These results support the conclusion that for dose ranging, depending on the demands of the clinical situation, one should use either the cross-over or the dose-escalation design.

Algorithms↗