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Biomedical subjects

T Kodama

Publications and source records attributed to T Kodama.

At least 505 records · Page 28Linked to original sources

Transconjunctival and transantral approaches are combined with antral wall bone graft to repair orbital floor blow-out fractures.

Orbital floor blow-out fractures in two patients were surgically repaired. The transconjunctival approach alone was unsuccessful in freeing the entrapped orbital contents, so the transantral approach with the use of antral wall bone graft was also used. The combined approaches produced good results. The transconjunctival approach supplemented with the transantral approach and bone graft may be a useful technique in the repair of orbital floor blow-out fractures.

Adolescent↗

Differential expression of scavenger receptor isoforms during monocyte-macrophage differentiation and foam cell formation.

Scavenger receptors mediate binding and uptake of chemically modified lipoproteins. cDNA cloning of the human macrophage scavenger receptor (MSR) reveals the presence of two mRNA species, the type I and II isoforms, which are generated by 3' alternative splicing of a single MSR gene and translated into two proteins with different C-terminal domains. We studied MSR isoform expression during the differentiation from circulating monocytes to adherent macrophages and subsequently to lipid-laden foam cells. Differentiation from monocyte to macrophage was associated with a prominent increase in MSR expression on the mRNA, protein, and cell surface levels, leading to an increased uptake of acetylated low-density lipoprotein (LDL). Further analyses of mRNA and proteins revealed that both MSR isoforms were present in low and approximately equal amounts on the surface of CD14+ peripheral blood monocytes; these cells had approximately similar levels of type I and type II MSR mRNA species. During differentiation to macrophages, there was a rapid, selective increase in type I MSR mRNA, with type II mRNA being expressed at approximately the same level as in the monocyte. This, in turn, resulted in an increase in type I MSR protein on the cell surface during differentiation from monocyte to macrophage. Type I MSR mRNA also dominated during the transformation of macrophages to foam cells in the presence of acetylated LDL. These findings suggest that the increased uptake of modified LDL during differentiation from monocyte to macrophage is accomplished by a selective upregulation of type I MSRs on the mRNA level. The increased expression of type I MSRs may be important for foam cell formation.

Base Sequence↗

Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and scavenger receptor in human atherosclerotic lesions.

Macrophage- and smooth muscle cell (SMC)-derived foam cells are typical constituents of human atherosclerotic lesions. At least three receptor systems have been characterized that could be involved in the development of foam cells: alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP), scavenger receptor, and LDL receptor. We studied the expression of these receptors in human atherosclerotic lesions with in situ hybridization and immunocytochemistry. An abundant expression of alpha 2MR/LRP mRNA and protein was found in SMC and macrophages in both early and advanced lesions in human aortas. alpha 2MR/LRP was also present in SMC in normal aortas. Scavenger receptor mRNA and protein were expressed in lesion macrophages but no expression was found in lesion SMC. LDL receptor was absent from the lesion area but was expressed in some aortas in medial SMC located near the adventitial border. The results demonstrate that (a) alpha 2MR/LRP is, so far, the only lipoprotein receptor expressed in lesions SMC in vivo; (b) scavenger receptors are expressed only in lesion macrophages; and (c) both receptors may play important roles in the development of human atherosclerotic lesions.

Adult↗

[Anticoagulant effect of a single bolus injection of parnaparin sodium (LHG) on a hemodialysis model in dogs].

Hemodialysis was performed on dogs, following intravenous bolus injections of LHG at dosage levels of 50, 100 and 200 IU/kg and heparin at the levels of 100 and 200 IU/kg. LHG exerted dose-dependent anticoagulant effects and prolonged the hemodialysis time, compared to heparin with similar anti-Xa activity. When LHG was administered, the half-life of plasma anti-Xa activity was longer than that of heparin at similar anti-Xa activity. LHG prolonged the activated partial thromboplastin time (APTT) linearly and dose-dependently. However, the prolongation was much less than that of heparin, and the anticoagulant activity of LHG continued even after the APTT returned to the value before LHG administration. When LHG was administered, whole blood Xa activated coagulation time (XCT) and plasma Xa activated coagulation time (PXCT) were prolonged in a significantly greater degree compared to APTT. Therefore, XCT and PXCT were considered to be appropriate parameters for monitoring LHG. In the groups administered with LHG at 100 and 200 IU/kg, where hemodialysis could be continued for 8 hr, the tissue factor pathway inhibitor (TFPI) activity in the plasma tended to show a sustained increase. These findings suggested the possibility that not only the antithrombin III dependency mechanism but also the TFPI mechanism contributed to a longer LHG hemodialysis duration compared to heparin administration.

Animals↗

A positive correlation between T-cell-receptor mutant frequencies and dicentric chromosome frequencies in lymphocytes from radiotherapy patients.

Dose estimates for the assessment of future risks, following accidental exposure to radiation, for certain diseases such as cancer usually rely on both physical and biological quantitative analyses. A traditional biological method of choice is the measurement of chromosome aberration frequencies in peripheral-blood lymphocytes. However, thorough examination of large sample populations is time and labor intensive. Recently, it became possible to measure mutant frequencies in T lymphocytes; one method is a colony assay at the HPRT gene, and the other is a flow-cytometric assay at the T-cell-receptor (TCR) gene. To test for the possible use of these mutation assays, concurrent measurements were taken on blood samples from women who previously received a full course of radiation therapy for gynecological cancer. The results showed that the frequency of TCR mutants correlated reasonably well with that of dicentric chromosomes, whereas the frequency of HPRT mutants did not. Possible uses of the TCR mutation assay in combination with the conventional chromosome analysis or micronucleus assay after exposure of a relatively large population are discussed.

Chromosome Aberrations↗

Structure and ANR-dependent transcription of the nir genes for denitrification from Pseudomonas aeruginosa.

In the denitrification gene cluster from Pseudomonas aeruginosa, an operon encoding three open reading frames (nirQ, ORF2, ORF3) was upstream of the structural gene for nitrite reductase (nirS) as a divergent transcriptional organization. A nucleotide-binding protein encoded by nirQ was 76% identical to the Pseudomonas stutzeri nirQ gene product, which was shown to be necessary for activating nitrite and nitric oxide reductases. The gene product of ORF2 was homologous to subunit III of cytochrome oxidases. The nirQ gene was transcribed under denitrifying conditions. The intergenic region of nirS and nirQ has only one binding motif for ANR, a regulatory protein for anaerobic gene expression correspond to FNR in E. coli. Complementation analyses showed that the transcription of both nirS and nirQ completely depended on ANR.

Amino Acid Sequence↗

Cloning and sequence of the L2 form of RubisCO from a marine obligately autotrophic hydrogen-oxidizing bacterium, Hydrogenovibrio marinus strain MH-110.

A form II ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) gene was isolated and sequenced from a marine hydrogen-oxidizing bacterium, Hydrogenovibrio marinus strain MH-110. To our knowledge, this is the first report for the sequence of a form II (L2-form) RubisCO gene derived from a chemolithoautotrophic bacterium. The form II RubisCO gene coded for 463 amino acid residues (1389 bp, M(r) = 50,655). The deduced amino acid sequence had high homology with those of the L2-form RubisCO of Rhodospirillum rubrum (63%) and the L4-form RubisCO from Rhodobacter sphaeroides (62%), but low similarity to other L8S8 form RubisCOs (under 40%).

Amino Acid Sequence↗

[Single-dose toxicity study and twenty-eight-days intravenously repeated dose toxicity study of desethyl-piperacillin in rats].

Desethyl-piperacillin (desethyl-PIPC) is an active metabolite of PIPC which was newly found in clinical field. We carried out a single intravenous toxicity study at the dosage of 2000 mg/kg, and 28-days intravenous toxi-city study at the daily dosage of 400 mg/kg followed by 28-days recovery study using both sexes of rats. The following results were obtained. In the single dose toxicity study, no deaths occurred in rats injected 2000 mg/kg of desethyl-PIPC, therefore it is presumed that minimal lethal dose of desethyl-PIPC is over 2000 mg/kg in both sexes. As clinical signs, decrease in locomotor activity, deep breath and loose stool were observed. In the patho-logical study, dilatation of cecal lumen was observed macroscopically, but no significant changes were observed histologically. In the repeated dose toxicity study, loose stool, increase in water consumption, dilatation of cecal lumen and increase in its weight were noted. These abnormal findings were considered to be due to antimicrobial activity of desethyl-PIPC. In addition, decrease in the ratio of serum gamma-globulin and increase in the ratio of alpha 1-globulin were observed, but A/G ratio was not affected. After withdrawal of desethyl-PIPC administration, these abnormal findings tended to disappear. As mentioned above, the minimal lethal dose of desethyl-PIPC is over 2000 mg/kg in the single dose toxicity study and abnormal signs were slight in the repeated dose toxicity study at the dosage of 400 mg/kg of desethyl-PIPC for 28 days in rats. It is, therefore, concluded that desethyl-PIPC is a low toxic metabolite of PIPC.

Alpha-Globulins↗

Retroperitoneal fibrosis leading to extrahepatic portal vein obstruction.

A very rare case of highly probable retroperitoneal fibrosis leading to extrahepatic portal obstruction is described. The patient was a 44-year-old woman with right pleural effusion and splenomegaly. Computed tomography indicated a large accumulation of soft tissues in the retroperitoneum, and abdominal angiography showed extensive portal obstruction. A twenty-year-long abuse of analgesics is suspected to have caused the retroperitoneal fibrosis.

Adult↗

Magnetic resonance imaging in patients with sudden deafness.

Although many theories on the etiology of sudden deafness have been proposed, the main pathological focus remains uncertain. In this study, MR examinations were performed on patients with unilateral sudden deafness to study the relationship between MRI findings and response to treatments, i.e. amidotrizoate, steroid, or both. In 7 out of 30 cases, the cochlea and/or the vestibule showed higher signal intensity on proton density and T2-weighted images on the diseased side (MRI positive cases). These findings suggest changes in the chemical composition of the perilymph and/or the endolymph, since proton density and T2-weighted images reflect water content. It appears that MRI positive sudden deafness is more difficult to cure even with the use of amidotrizoate or steroid than MRI negative sudden deafness. Amidotrizoate seems to be more effective in MRI negative sudden deafness. MRI would help us to further classify the etiology of sudden deafness.

Adolescent↗

Effect of aging on glucose tolerance in spontaneously hypertensive rats.

We studied the age-related changes of glucose tolerance in female spontaneously hypertensive rats (SHR) that did not become obese with aging. Oral glucose tolerance test was performed in young (3 months), middle-aged (6 to 11 months), and aged (26 months) SHR. Fasting plasma glucose was significantly lower in aged SHR than in young SHR. The increase in plasma glucose after glucose administration over fasting level was significantly higher in aged SHR than in middle-aged SHR, but did not differ between young and aged rats. Pancreatic islet size and pancreatic immunoreactive insulin content were similar between young and aged SHR. The present study demonstrated that glucose tolerance did not deteriorate in SHR with aging, while genetic hypertension persisted. This suggests that the persistence of hypertension per se may not affect glucose tolerance in SHR.

Aging↗

Characterization of aggregated low density lipoproteins induced by copper-catalyzed oxidation.

Oxidation of low density lipoproteins (LDL) has been shown to lead to enhanced uptake by macrophages mediated by the scavenger receptor. In the present study, changes in LDL induced by copper-catalyzed oxidation were investigated using gel permeation chromatography (GPC), and the results were compared with several parameters of oxidized LDL (ox-LDL). When LDL at 200 micrograms/ml was oxidized with 10 microM Cu2+ at 37 degrees C for up to 24 hours, increases in thiobarbituric acid-reactive substances and electrophoretic mobility were first observed within 3 hours. An increase in fluorescence and a decrease in intact apolipoprotein B (apoB) were than observed in parallel with an increase in 125I-LDL degradation by macrophages after 6 hours. Finally, LDL aggregation separated by liquid chromatography was observed after 24 hours. The aggregated and monomeric fractions of ox-LDL were analyzed and the results compared with the monomeric fraction of native LDL. Both fractions of ox-LDL contained hardly any intact apoB and showed an intense fluorescence. The electrophoretic mobility increment of aggregated ox-LDL was almost half that of monomeric ox-LDL, yet the lysine residues of aggregated ox-LDL were more extensively decreased than those of monomeric ox-LDL. Degradation of aggregated ox-LDL by macrophages showed a slightly greater increase than that of monomeric ox-LDL. GPC analysis is a useful method to estimate the LDL aggregation, and these results provide a basis to investigate the formation of aggregated LDL.

Animals↗

Prevalence of HBV and HCV infection in Japanese patients with hepatocellular carcinoma.

The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was investigated in 63 Japanese patients with hepatocellular carcinoma (HCC). HBV infection was confirmed by measuring hepatitis B surface antigen and HBV-DNA in the serum, and HCV infection was confirmed by measuring antibody to HCV using a 2nd generation test and HCV-RNA in serum. Some 54.0% of the patients had HCV infection only, 27.0% had HBV infection only, and 9.5% had both HCV and HBV infection. Only 9.5% of HCC patients had neither HCV nor HBV markers. These results indicate that, in Japan, HCV and HBV infection is an important factor associated with HCC, and that the hepatitis virus may have a role in the carcinogenesis of HCC.

Adult↗

Genome DNA analysis and genotyping of clinical isolates of Helicobacter pylori.

The genotype of genome DNA from seventeen clinical isolates of Helicobacter pylori by pulsed-field gel electrophoresis (PFGE) and arbitrarily primed polymerase chain reaction (AP-PCR) was determined. Three restriction enzymes, Apa I, Kpn I and Not I, were found to produce distributions of DNA fragments which were useful for analysis of the chromosome-sized DNA from H. pylori NCTC11637T by PFGE. Many of the isolates of H. pylori could not be genotyped by PFGE after digestion reaction with Apa I, Kpn I, and Not I. When AP-PCR with a ten-nucleotide primer was performed using the chromosomal genomic DNA from the isolates as templates, fifteen distinctly different profiles were obtained from the seventeen isolates. Thus, genotyping of the isolates was possible where PFGE profiles had not previously been informative. The results suggest that AP-PCR is more suitable for genotyping of clinical isolates of H. pylori in Japan than PFGE.

DNA, Bacterial↗

Inverse relationship between serum cholinesterase activity and the administration of cyclophosphamide: an index of cyclophosphamide therapy.

To determine whether serum cholinesterase activity can be a monitoring index of cyclophosphamide therapy in patients with steroid-resistant glomerulopathy, we compared the cholinesterase activity of 37 patients who received a combined therapy that included the use of cyclophosphamide, prednisolone, antiplatelet drugs, and anticoagulant drugs, with the cholinesterase activity of 25 patients who received prednisolone therapy that excluded cyclophosphamide from the combined therapy. In the prednisolone and the combined groups, cholinesterase activity declined as shown in the following formula: Y = 371-26.4 x log(X): (r2 = 0.28), Y = 444-147.7 x log(X): (r2 = 0.95), respectively. (Y: cholinesterase activity, X: the day after treatment). In the combined therapy group, the prevalence of adverse reactions following treatment in the subgroup below 200 U/l of cholinesterase activity was significantly greater (P < 0.01) than that in the subgroup above 200 U/l of cholinesterase activity. However, there was no significant difference (P < 0.25) in the prevalence of adverse reactions between the subgroups with more or less than 184 U/l of cholinesterase activity following treatment. These results suggest the importance of not going below 200 U/l of cholinesterase activity after treatment when the normal cholinesterase activity range is between 300 and 760 U/l (e.g. less than 65% of the lowest value of the normal range of other hospitals) in order to eliminate the hazards of cyclophosphamide to the patients with steroid-resistant glomerulopathy.

Adolescent↗

[Regulation of gene expression by cholesterol and macrophage scavenger receptor].

Cellular cholesterol level is strictly regulated by the synthesis and the incorporation of cholesterol. Cholesterol synthetic enzymes and lipoprotein receptors are regulated mainly at the transcriptional level. Recently, sterol regulatory element binding proteins (SREBPs) which induce LDL receptor expression, were cloned and the mechanism of sterol-mediated gene regulation was proposed. Cholesterol synthesizing enzymes such as HMG-CoA reductase, farnesyl pyrophosphate synthase and squalene synthase are also regulated by the cellular cholesterol level, but it is suggested that SREBPs are not play critical role in their regulation. Scavenger receptors also uptake cholesterol into macrophage, but the receptors are not regulated by the cellular cholesterol level and this leads to the abnormal accumulation of cholesterol in macrophages.

Alkyl and Aryl Transferases↗

Expression of histamine H2 receptor in Chinese hamster ovary cells: a probe to study the desensitization mechanism.

Canine histamine H2 receptor DNA, cloned by polymenase chain reaction (PCR), was transfected into Chinese hamster ovary cells using an expression vector. The expression of H2 receptors was demonstrated by immunoblotting with specific antibodies and the binding of tiotidine, an H2 receptor antagonist. H2 receptor-specific cAMP production was observed only in cells expressing canine H2 receptors. Preincubation of transfected cells with 10 microM histamine for 10 or 60 min at 37 degrees C decreased both the maximal response and the sensitivity of the subsequent histamine-stimulated cAMP production, showing desensitization. Under these circumstances, decreases in tiotidine binding without changes in affinity in intact cells and also in the membrane were observed, whereas there was no decrease in total H2 receptor number. Thus, desensitization of histamine H2 receptor was associated with the sequetration of receptors.

Animals↗

Endocytic pathway of scavenger receptors via trans-Golgi system in bovine alveolar macrophages.

BACKGROUND: The scavenger receptors are trimeric membrane glycoproteins present on the surface membrane of macrophages and macrophage-derived foam cells and are implicated in the deposition of cholesterol in the arterial walls during atherogenesis. This receptor mediates endocytosis of a diverse alley of negatively charged macromolecules including modified low density lipoproteins. EXPERIMENTAL DESIGN: We tried biochemical and morphologic approaches to elucidate in more detail the endocytic and intracellular pathway of the scavenger receptors during endocytosis of acetylated low density lipoproteins (AcLDL) and oxidized LDL (OxLDL) by bovine alveolar macrophages. Biochemically, cell interaction and subsequent intracellular degradation of AcLDL and OxLDL were examined using [125I]AcLDL or [125I]OxLDL. At the ultramorphologic level, the scavenger receptors were detected by a mouse monoclonal antibody against bovine macrophages, D2, with colloidal gold particles (AcLDL-Au or OxLDL-Au particles) as tracer of ligands. RESULTS: The biochemical studies demonstrated that after binding of AcLDL and OxLDL to the cell surface, these ligands were internalized and degraded intracellularly. Immunoelectron microscopy revealed that after a 2-hour incubation at 4 degrees C AcLDL-Au or OxLDL-Au particles were bound to the scavenger receptors present on the cell surfaces. Upon a temperature shift from 4 to 37 degrees C, these particles were concentrated in coated pits and internalized in endosomes. After subsequent dissociation of the particles from the receptors within the endosomes, the ligands were transported to secondary lysosomes, the receptors were transported to a trans-Golgi system. In the Golgi complex, the receptors were packed in secretory vesicles and recycled to the cell surface membrane. The transport and recycling of the receptors via the trans-Golgi system were completely inhibited by incubation below 18 degrees C or pretreatment with monensin. CONCLUSIONS: These results suggest that during endocytosis of modified low density lipoprotein, the Golgi complex plays a crucial role in sorting and recycling of the scavenger receptors in macrophages.

Animals↗