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Biomedical subjects

T Takagi

Publications and source records attributed to T Takagi.

At least 361 records · Page 20Linked to original sources

[Two cases of malignant lymphoma with initial symptoms like orbital cellulitis and complicated by hemophagocytosis].

We reported 2 patients with malignant lymphoma complicated by hemophagocytic syndrome. Their clinical signs at onset were those of orbital cellulitis. Lymphoma complicated with hemophagocytosis is called lymphoma-associated hemophagocytosis syndrome (LAHS) and its prognosis is reported to be very poor. So far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. Within 6 months after the first opthalmological examination, both died. When orbital cellulitis is suspected and antibiotic therapy is ineffective, we should suspect hemophagocytic syndrome (HPS) and should examine serum ferritin which is a good markers of HPS. Early biopsy and consultation with a hematologist are very important.

Adolescent↗

[Multi-drug resistance of serovar E strains in clinically isolated Pseudomonas aeruginosa and analysis of genome pattern].

We analyzed the in vitro antibiotic susceptible pattern and serovar for 132 strains of pseudomonas aeruginosa (98 from inpatients and 34 from outpatients) isolated at Showa University hospital from September to December of 1993. The ratio of resistant strains was 38.6% for carbenicillin, 12.1% for piperacillin, 12.9% for ceftazidime, 12.1% for cefsulodin, 17.4% for cefoperazone, 9.1% for cefclidin, 24.2% for cefpirome, 7.6% for imipenem, 17.4% for amikacin, 16.7% for aztreonam, 89.4% for minocycline and 33.3% for ofloxacin. The incidence of resistance against minocycline, carbenicillin, ofloxacin was markedly high. Among the 132 tested strains of Pseudomonas aeruginosa, 16 were multi-drug resistant strains (i.e., resistant to more than 8 drugs out of 12 drugs), and 14 of the multi-drug resistant strains (87.5%) were isolated from inpatients. Multi-drug resistant strains were isolated most frequently from urine specimens. The antibiotics that remained effective against the multi-drug resistant strains included amikacin, imipenem, cefclidin and cefsulodin. The serovar of 116 strains (resistant to up to 7 drugs) was 27 for G, 24 for B, and 19 for E, and 15 of the 16 multi-drug resistant strains showed serovar E. Restriction enzyme SpeI digestion analysis (using pulse field electrophoresis) of P. aeruginosa having serovar E revealed common 650kb and 540kb bands in multi-drug resistant strains. The genome pattern was quoted for serovar E strain according to the restriction enzyme digestion pattern and was shown to be useful for tracing the route of infection.

Drug Resistance, Microbial↗

[Suppression of experimental autoimmune uveitis by energy restriction].

The effects of energy restriction on experimental autoimmune uveitis (EAU) were investigated. Seven-week-old, male Lewis rats were divided into three groups. Experiment A) A control group was fed ad libitum, a second group was given 50% calorie restricted food from the day of immunization, and a third group was given 50% calorie restricted food from 2 weeks before immunization. Experiment B) A control group was fed ad libitum, a second group was given 25% calorie restricted food from 4 weeks before immunization, and a third group was given 50% calorie restricted food 4 weeks before immunization. All rats were immunized with interphotoreceptor retinoid-binding protein (IRBP). In experiment A), in the group given 50% calorie restricted food from 2 weeks before immunization, and in experiment B), in the group given 50% calorie restricted food from 4 weeks before immunization, the onset of EAU was significantly delayed, the clinical symptoms were lessened, and delayed hypersensitivity against IRBP was suppressed. Clinically and histologically, the severity was also low. In the group given 50% calorie restricted food from 4 weeks before immunization, the titer of anti-IRBP antibody was also significantly lower than in the control group.

Animals↗

[A case study of immunohistochemical findings of rheumatic pseudocystic lesions in the femoral lateral condyle and tibial plateau--the comparison with synovial lesions].

Rheumatoid pseudocysts of which pathogenesis are not well known, are commonly observed in the major joints of the body, especially knees in rheumatoid patients. This report investigated the pseudocysts in the knee of a rheumatoid patient radiologically and immunohistochemically. A sixty-three-year-old woman with rheumatoid arthritis who had pseudocysts in the femoral lateral condyle and tibial plateau was hospitalized to have the lesions surgically removed. The MRI findings showed a connection between the pseudocysts and the joint cavity. A window of 1 x 1 cm2 was made at the tibial anterior cortex and the contents of the pseudocyst were resected and hydroxyapatite granules were inserted into the lesion after the removal of the pseudocyst tissue. In the histological findings, the specimen from the tibial pseudocyst revealed fibrous connective tissue with a few inflammatory cells, while the synovial specimen revealed the fibrous tissue with intense inflammatory cells infiltration forming lymphoid follicules. In immunohistochemical findings, both specimens showed positive with anti-HLA class I, anti-HLA DR, anti-CD44 and anti-HSP70 antibodies. The pathological findings of the pseudocystic lesion were similar to those of synovia, and it was considered that the synovia had invaded into the bone and formed the pseudocystic lesion. The MRI findings also support this hypothesis. The pseudocystic lesion was surrounded by bone and it was isolated from cytokain-rich joint effusion. This isolation from rheumatic joint effusion may explain the weaker inflammation of the pseudocystic lesion than that of synovia.

Arthritis, Rheumatoid↗

Pseudoaneurysm and ventricular septal rupture complicated with inferior myocardial infarction diagnosed by two-dimensional and Doppler echocardiography: case report.

A 72-year-old woman with inferior myocardial infarction presented with both a pseudoaneurysm and a ventricular septal rupture detected by two-dimensional and Doppler echocardiography. The pseudoaneurysm originated from the junctional area between the inferior portion of the ventricular septum and posterior left ventricular wall. The short-axis view of two-dimensional echocardiography revealed an abrupt discontinuity of the junctional area and an echo-free space behind the left ventricular cavity. The communication orifice was 5 mm wide. Color Doppler echocardiography showed a left-to-right shunt flow from the pseudoaneurysm to the right ventricle was visualized. Combined use of two-dimensional and color Doppler echocardiography was useful for detecting a pseudoaneurysm resulting in rupture of the ventricular septum.

Aged↗

[Automatic assessment of left ventricular cavity area by the automated contour tracking method].

Measurements of left ventricular cavity area by the manual tracing method from apical four-chamber views were compared with those using the automated contour tracking (ACT) method. Nine consecutive patients in whom clear images were obtained by two-dimensional echocardiography were studied, and left ventricular end-diastolic, end-systolic areas an fractional area changes were calculated using the ACT method. The ACT method slightly underestimated left ventricular cavity areas, but excellent correlations were obtained with left ventricular end-diastolic and end-systolic areas between the ACT and manual methods (r = 0.99, SEE = 1.5 cm2; r = 0.99, SEE = 1.2 cm2; respectively). Manual tracing fractional area change correlated well with that by the ACT method (r = 0.95, SEE = 3.4%). The ACT method provides accurate estimates of the area of the left ventricular cavity.

Cardiac Volume↗

Progressive zonal outer retinitis.

A 27-year-old woman with uniocular progressive zonal outer retinitis was examined. The retinitis area was curvilinear and gray, with zonal opacification. It enlarged centrifugally and concentrically, with narrowing of the zonal opacification. Results of perimetry and electroretinography showed that the outer retina was primarily affected. Damage was more severe in the photoreceptor cones than in the rods. Peripheral retinal phlebitis was seen on fluorescein angiography. Intraretinal pigment migration with retinal pigment epithelial atrophy occurred in the macula as sequelae.

Adult↗

[Quantitative analysis of 99mTc-GSA liver scintigraphy with graphical plot method].

99mTc-galactosyl human serum albumin (99mTc-GSA) is a newly developed receptor-binding agent, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. Liver scintigraphy using 99mTc-GSA was performed on 65 patients with liver diseases. Dynamic data were obtained by gamma camera during 20 minutes after the intravenous injection of 3 mg (185 MBq) of 99mTc-GSA. The maximum removal rate of 99mTc-GSA (denoted as P(2)) was measured by two methods: nonlinear five-compartment model analysis adopting the Michaelis-Menten constant for the transfer of 99mTc-GSA from hepatic blood to receptor, and a graphical plot using compartmental dose curves. The graphical plot could estimate easily the maximum removal rate in terms of two data points of 0 and 1 minutes without nonlinear least squares and numerical integration. The results indicated that the maximum removal rate was decided immediately after the intravenous injection of 99mTc-GSA. Although 99mTc-GSA is recognized to accumulate nonlinearly on the liver, the rate constant P(2)*(1/min) of transfer from hepatic blood to the receptor was estimated by graphical plot, assuming a linear five-compartment model. P(2)*Km, which was given by the product of the rate constant P(2)* and the Michaelis constant Km, was well correlated with P(2). Next, for 99mTc-GSA liver scintigraphy, we applied a Patlak plot that was applicable to the linear system, and the rate constant Ku of transfer from extrahepatic blood to the liver was estimated. From the results of graphical plot, it was theoretically shown that Ku represented P(2). This was confirmed by clinical data.

Adult↗

[Serial change of mitral regurgitation after anterior mitral valve repair using polytetrafluorethylene chordae: evaluation by transesophageal echocardiography].

The results of anterior mitral leaflet repair were evaluated by the serial change of mitral regurgitation (MR) using transesophageal echocardiography (TEE) in 24 patients undergoing mitral valve repair for anterior leaflet prolapse during 1988 to 1994, who were examined by TEE immediately after operation, 1 month after operation, and late after operation (mean 15 months). Chordal replacement using polytetra-fluorethylene chordae was performed in 15 patients (PTFE group), and not performed in 9 patients (non-PTFE group). MR jet area late after operation was significantly smaller in the PTFE group than in the non-PTFE group (2.2 +/- 2.3 vs. 4.6 +/- 2.3 cm2, p < 0.05). Moderate to severe MR was observed in four patients (27%) in the PTFE group, and six (67%) in the non-PTFE group late after operation. The thickness of the mitral leaflet before operation was more than 5 mm in all patients with more than moderate MR late after operation in the PTFE group. Chordal replacement using polytetrafluorethylene chordae showed better results compared with conventional mitral valve repair without polytetrafluorethylene chordae over the follow-up period of 15 months.

Aged↗

[Prognostic value of serial Doppler echocardiographic follow-up of transmitral flow patterns in patients with congestive heart failure who presented with pulmonary edema].

The predictive value of serial Doppler echocardiographic follow-up of transmitral flow patterns for the prognosis of patients with congestive heart failure who presented with pulmonary edema was evaluated in 80 consecutive patients with decreased left ventricular systolic function (ejection fraction < 40%). Restrictive patterns [peak early diastolic filling velocity (E)/peak late diastolic filling velocity (A) ratio (E/A) > 2 and/or deceleration time for E wave to decline to baseline (DcT) < 150 msec] were observed in 72 patients (90%) on admission. After intensive therapy, DcT showed a nonrestrictive pattern in 38 of 72 patients (53%). The survival rates at 1 year was 50% for the restrictive group, and 97% for the nonrestrictive group. E/A showed a nonrestrictive pattern in 37 of 56 patients (66%). The survival rates at 1 year was 86% for the restrictive group, and 58% for the nonrestrictive group. Serial Doppler echocardiographic follow-up of transmitral flow patterns is useful in predicting the prognosis in patients with congestive heart failure who presented with pulmonary edema.

Aged↗

Purification, characterization, and cDNA cloning of a 27-kDa lectin (L10) from horseshoe crab hemocytes.

We separated granular components of horseshoe crab hemocytes by a combination of centrifugation on sucrose density gradient and high performance liquid chromatography, and a 27-kDa protein termed L10 was found to be a major component in the large granules (Shigenaga, T., Takayenoki, Y., Kawasaki, S., Seki, N., Muta, T., Toh, Y., Ito, A., and Iwanaga, S. (1993) J. Biochem. (Tokyo) 114, 307-316). In the present work, lectin activity of this protein and its unique primary structure were elucidated. L10 was purified by four steps of chromatography, including dextran sulfate-Sepharose CL-6B, CM-Sepharose CL-6B, Sephacryl S-200, and Mono S. At least three 27-kDa isoproteins, named L10a, L10b, and L10c, were isolated. Their amino acid compositions were almost indistinguishable, and there were no amino sugars. All the isoforms had hemagglutinating activity against human A-type erythrocytes, in a Ca(2+)-independent manner with L10b showing the highest activity. The L10b-mediated hemagglutination was inhibited in the presence of N-acetylglucosamine or N-acetylallolactosamine, and the association constant (Ka) between L10b and N-acetylglucosamine was 1.95 x 10(4) M-1. Furthermore, L10b specifically agglutinated Staphylococcus saprophyticus KD. Ultracentrifugation analysis revealed that L10b is present in monomer form in solution. A cDNA coding for an isoform of L10 was isolated from a hemocyte cDNA library. The open reading frame of the 768-base pair cDNA coded for the signal sequence of 19 residues. The mature protein had 236 residues with the calculated molecular weight of 26,757. Amino acid sequences of the peptides derived from L10c exactly corresponded to the predicted sequence of the cDNA, whereas amino acid replacements of Ile-129 to Val and His-213 to Tyr existed both in L10a and L10b, suggesting that the cDNA codes for L10c. Cysteine was absent and there were five tandem repeats with 47 amino acids in each segment with internal sequence identities of 49-68%. The entire amino acid sequences had no significant sequence similarity with other known proteins.

Agglutination Tests↗

Activation of protein kinase C by oxidized diacylglycerols.

The effects of 1,2-diacylglycerol hydroperoxide (DAG-OOH), its alcohol (DAG-OH), "unoxidized" 1,2-diacylglycerol (DAG), 1,2-dioleoylglycerol (DOG), and phorbol 12-myristate acetate (PMA) on the activity of protein kinase C (PKC) isolated from rat brain were examined in the presence and absence of phosphatidylserine (PS) and calcium ion. Both DAG-OOH and DAG-OH stimulated the activity of PKC dose- and time-dependently. The ability of additives for PKC activation increased in the order of DOG, DAG << DAG-OOH, DAG-OH < PMA. DAG-OOH and DAG-OH activated PKC even in the absence of PS and calcium ion as PMA does. If DAG-OOH and DAG-OH are released from the oxidized biomembranes by the action of phospholipase C, these components may act like PMA and serve to activate the PKC-dependent signal transduction system.

Animals↗

Cloning of a novel RNA binding polypeptide (RA301) induced by hypoxia/reoxygenation.

Astrocytes have a critical role in the neuronal response to ischemia, as their production of neurotrophic mediators can favorably impact on the extreme sensitivity of nervous tissue to oxygen deprivation. Using a differential display method, a novel putative RNA binding protein, RA301, was cloned from reoxygenated astrocytes. Analysis of the deduced amino acid sequence showed two ribonucleoprotein domains and serine/arginine-rich domains, suggestive of their function as RNA splicing factor. Northern analysis displayed striking induction only in cultured astrocytes within 15 min of reoxygenation and reached a maximum by 60 min after hypoxia/reoxygenation. Immunoblotting demonstrated expression of an immunoreactive polypeptide of the expected molecular mass, 36 kDa, in lysates of hypoxia/reoxygenated astrocytes. Induction of RA301 mRNA was mediated, in large part, by endogenously generated reactive oxygen species, as shown by diphenyl iodonium, an inhibitor of neutrophil-type nicotinamide adenine dinucleotide phosphate oxidase which blocks oxygen-free radical formation by astrocytes. Similarly, increased expression of RA301 in supporting a neurotrophic function of astrocytes was suggested by inhibition of interleukin-6 elaboration, a neuroprotective cytokine, in the presence of antisense oligonucleotide for RA301. These studies provide a first step in characterizing a novel putative RNA binding protein, whose expression is induced by oxygen-free radicals generated during hypoxia/reoxygenation, and which may have an important role in redirection of biosynthetic events observed in the ischemic tissues.

Aerobiosis↗

Mechanism of dimer formation of the 90-kDa heat-shock protein.

This study describes the mechanism of homodimer formation of the 90-kDa heat-shock protein (HSP90). In eukaryotic cells, there are two HSP90 isoforms, alpha and beta, encoded by two separate genes. HSP90 alpha exists predominantly as a homodimer, HSP90 beta mainly as a monomer. Analysis by native PAGE revealed that bacterially expressed HSP90 alpha fused to glutathione S-transferase (GST) existed as a high-molecular-mass oligomer, and was converted to a homodimer following removal of the fusion enzyme by thrombin cleavage. A deletion mutant, HSP90 alpha D44-603, formed a monomer and an N-terminal truncated mutant, HSP90 alpha 533-732, existed as a dimer, indicating that the dimer-forming ability resides somewhere in the C-terminal 200 amino acids. Limited proteolysis of the C-terminal 200 amino acids of HSP90 alpha with chymotrypsin produced the C-terminal 16-kDa fragment (Met628/Ala629-Asp732) and its adjacent more N-terminal 13-kDa fragment (Val542-Tyr627/Met628). Size-exclusion HPLC and two-dimensional PAGE analyses demonstrated that these two chymotryptic fragments bound each other. The C-terminal 198 amino acids as well as the full-length form of HSP90 beta revealed a lower dimer-forming activity than HSP90 alpha. Expression of the chimeric proteins at the C-terminal 198 amino acids of the alpha and beta isoforms further indicated that the 16 amino acid substitutions locating between amino acids 561 and 685 account for the impeded dimerization of HSP90 beta. A leucine zipper motif (Met402-Leu423) was unlikely to be involved in the dimer formation. Taken together, these results indicate that the dimeric structure of HSP90 alpha is mediated by the C-terminal 191 amino acids and consists of duplicate interactions of the C-terminal region (Met628/Ala629-Asp732) of one subunit and the adjacent more N-terminal region (Val542-Try627/Met628) of the other subunit.

Amino Acid Sequence↗

Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization efficiency and toxicity.

PURPOSE: A new 2-nitroimidazole nucleoside radiosensitizer, PR-350 (1-[1',3',4'-trihydroxy-2'-butoxy]-methyl-2-nitroimidazole), has been reported to be as efficient as and less toxic than etanidazole. This compound is racemic, and it was recently optically resolved into two isomers, PR-68 (2'R,3'S type) and PR-69 (2'S,3'R type). The other two isomers, PR-28 (2'S,3'S type) and PR-44 (2'R,3'R type), were asymmetrically synthesized. In the present study, we investigated the properties, sensitizing activity, and toxicity of PR-350 and the four optical isomers in comparison with those of other 2-nitroimidazole hypoxic cell radiosensitizers, etanidazole, KU-2285, KIN-804, and RP-170. Because PR-350 and PR-28 can be industrially synthesized, we evaluated whether either of these two drugs are suitable for further investigation. METHODS AND MATERIALS: In an in vitro study, EMT-6 cells were irradiated at a dose of 1-3 Gy under hypoxic conditions in the presence of the drugs at a concentration of 1 mM. A combined cytokinesis-block micronucleus and chromosomal aberration assay was performed. To assess the in vivo effects, colony assay and growth delay assay were performing using SCCVII tumor-bearing C3H mice. The mice received 16-24 GY 10-40 min after administration of 50-200 mg/kg of the drugs. Toxicity and pharmacokinetics in mice were also investigated. RESULTS: The sensitizer enhancement ratio (SER) in the in vitro cytokinesis-block micronucleus assay increased in the following order: PR-69 (1.27) approximately equal to PR-28 (1.31) approximately equal to PR-44 (1.38) approximately equal to PR-350 (1.41) approximately equal to PR-68 (1.47) < etanidazole (1.79) < KIN-804 (2.03) approximately equal to KU-2285 (2.30). The SER at a dose of 200 mg/kg and at an interval of 20 min (optimal interval) in the in vivo-in vitro colony assay increased as follows: PR-44 (1.26) approximately equal to PR-28 (1.29) < PR-69 (1.34) approximately equal to etanidazole (1.35) approximately equal to PR-350 (1.36) < RP-170 (1.41) approximately equal to PR-68 (1.41) < KU-2285 (1.49). The growth delay assay also showed that PR-350 was less efficient than KU-2285 and more efficient than PR-28. PR-350 and the four isomers had similar reduction potentials, but PR-28 and PR-44 were more hydrophilic than PR-68 and PR-69. The LD50 in mice were 5.8 g/kg for PR-350, approximately 7 g/kg for PR-28, 4 g/kg for PR-68, and 6 g/kg for PR-44 and PR-69. The concentration of PR-28 in the murine sciatic nerve was lower than that of PR-350. CONCLUSION: In vivo radiosensitizing activity differed among the four optical isomers, which appeared to be due, at least in part, to differences in lipophilicity. Although PR-28 was the least toxic, its low sensitization efficiency does not warrant clinical trials. Among the PR compounds, PR-68 appears to be most efficient, but optical resolution of PR-68 from PR-350 is expensive, and asymmetrical synthesis of PR-68 is not established. Therefore, PR-350 seems to be most suitable for further investigation among the PR-350 series compounds, considering its higher efficiency compared with PR-28 and PR-44, and established synthesis.

Animals↗

Purification of an ATP-dependent actin-binding protein from a lower eukaryote, Physarum polycephalum.

A novel protein with a molecular mass of 55 kDa, as determined by SDS-PAGE, was purified from plasmodia of Physarum polycephalum. The protein bound to actin filaments with a stoichiometry of 0.27 moles per mole of actin with an apparent dissociation constant of 4 x 10(-8) M. In the presence of ATP, the protein dissociated from actin filaments. Adenosine 5-(gamma-thio)triphosphate and adenyl-5'-yl imidodiphosphate also abolished the actin-binding activity of the protein, but GTP did not. Because the cytoplasmic concentration of ATP oscillates in association with the shuttle streaming of the cytoplasm, it is possible that this protein might be involved in the actin-linked regulation of cytoplasmic streaming.

Actins↗

Incilaria mucus agglutinated human erythrocytes.

The body surface mucus from the land slug, Incilaria fruhstorferi, not only opsonized sheep red blood cells (SRBC) and agglutinated human types A and B erythrocytes (HRBC) but also caused hemolysis of B type HRBC 12 h after agglutination. The mucus-induced hemagglutination was specifically inhibited by a low concentration of N-acetyl D-galactosamine (GalNAc), and all of this activity was completely inactivated by heating at 56 degrees C for 30 min. SDS-polyacrylamide gel electrophoresis of water soluble fraction of the mucus showed that this fraction contained several proteins, the molecular mass of the main band being 35 KD.

Animals↗

Modulation of the behavior of a protein in polyacrylamide gel electrophoresis in the presence of dodecyl sulfate by varying the cations.

The denaturation of Aspergillus oryzae alpha-amylase by dodecyl sulfates can be modulated by the change of cations among sodium, lithium, and several alkanolammonium ions. The denaturation can be detected by polyacrylamide gel electrophoresis in the presence of alkanolammonium dodecyl sulfates, particularly around 0 degree C where the denaturation reaction can be virtually frozen. The moderate stability of the amylase against denaturation by dodecyl sulfates helped to demonstrate the difference among the cations. We previously reported a significant difference among the dodecyl sulfates in their ability to dissociate chlorophyll-protein assemblies. The present results indicated that there is also a difference in the ability of the dodecyl sulfates to denature the amylase, a monomeric water-soluble protein. Two species, one retaining intact disulfide bonds and the other underwent a single sulfhydryl-disulfide exchange reaction, were generated during amylase denaturation by dodecyl sulfates.

Aspergillus oryzae↗